Sample records for ileal mucosal glutathione

  1. Mucosal characteristics of pelvic ileal pouches

    Microsoft Academic Search

    H J de Silva; P R Millard; M Kettlewell; N J Mortensen; C Prince; D P Jewell

    1991-01-01

    This study aimed to investigate the degree of colonic metaplasia in ileo - anal pouches. Biopsy specimens from 25 patients with functioning pouches, eight of whom had pouchitis, were studied using routine histology, mucosal morphometry, mucin histochemistry, and immunoperoxidase staining with monoclonal antibodies directed towards a 40kD colonic protein and a small bowel specific disaccharidase-sucrase isomaltase. Thirteen patients (including all

  2. Restorative proctocolectomy with ileal reservoir: pathological and histochemical study of mucosal biopsy specimens

    Microsoft Academic Search

    N A Shepherd; J R Jass; I Duval; R L Moskowitz; R J Nicholls; B C Morson

    1987-01-01

    Mucosal biopsy specimens from the ileal reservoirs of 92 patients who had undergone restorative proctocolectomy (12 with familial adenomatous polyposis, 78 with ulcerative colitis, and two with functional bowel disease) were studied. Chronic inflammation was found in almost all, as was villous atrophy of varying severity. Other changes included pyloric metaplasia and mucosal prolapse. Acute inflammatory changes and ulceration were

  3. Endorectal ileoanal anastomosis with isoperistaltic ileal reservoir after colectomy and mucosal proctectomy.

    PubMed Central

    Fonkalsrud, E W

    1984-01-01

    Forty-nine patients with chronic ulcerative colitis refractory to medical therapy and four with multiple polyposis have undergone total colectomy, mucosal protectomy, and endorectal ileal pull-through with ileoanal anastomosis at the UCLA Medical Center during the past 12 years (mean age, 19.4 years). Thirty-eight patients underwent second-stage closure of the ileostomy with construction of a side-to-side isoperistaltic ileal reservoir (mean, 6 months) after the ileal pullthrough operation. The anastomosis extended over a 20-30 cm distance and the lower end was placed within 6-8 cm of the ileonanal anastomosis. Transient reservoir inflammation, which occurred in half of the patients, was reduced by the use of oral metranidazole and was rarely found 6 months after operation. No patients died during the early or late post-operative periods. Cuff abscess in two patients and obstruction of the ileal reservoir outlet have required takedown of the reservoir (two patients) or temporary ileostomy (three patients). Of the 38 patients who have undergone lateral ileal reservoir construction, 33 have achieved a good to excellent result with complete continence and an average of five stools per 24 hours after 6 months. At least 12 patients now participate in competitive athletics; normal sexual activity has been achieved in all but one patient. Seven patients await construction of the reservoir. Although a technically difficult operation, the long-term results (mean, 19.4 months) indicate that the pullthrough operation is a good alternative to standard proctocolectomy. Images Fig. 1. PMID:6696530

  4. Internal anal sphincter function after total abdominal colectomy and stapled ileal pouch-anal anastomosis without mucosal proctectomy

    Microsoft Academic Search

    Ian C. Lavery; Wayne B. Tuckson; Kirk A. Easley

    1989-01-01

    A comparison, based on results from anal manometry and continence, was made between eight patients after circular stapled\\u000a ileal J-pouch-anal anastomosis without mucosectomy (Js) and seven patients after endoanal mucosal proctectomy and hand-sewn\\u000a ileal pouch-anal anastomosis (Jm). The mean and range from ileostomy closure were 3.5 months (1.5 to 12) and 21.7 months (13\\u000a to 32), respectively. The mean maximum

  5. An Ileal Crohn's Disease Gene Signature Based on Whole Human Genome Expression Profiles of Disease Unaffected Ileal Mucosal Biopsies

    PubMed Central

    Zhang, Tianyi; Song, Bowen; Zhu, Wei; Xu, Xiao; Gong, Qing Qing; Morando, Christopher; Dassopoulos, Themistocles; Newberry, Rodney D.; Hunt, Steven R.; Li, Ellen

    2012-01-01

    Previous genome-wide expression studies have highlighted distinct gene expression patterns in inflammatory bowel disease (IBD) compared to control samples, but the interpretation of these studies has been limited by sample heterogeneity with respect to disease phenotype, disease activity, and anatomic sites. To further improve molecular classification of inflammatory bowel disease phenotypes we focused on a single anatomic site, the disease unaffected proximal ileal margin of resected ileum, and three phenotypes that were unlikely to overlap: ileal Crohn's disease (ileal CD), ulcerative colitis (UC), and control patients without IBD. Whole human genome (Agilent) expression profiling was conducted on two independent sets of disease-unaffected ileal samples collected from the proximal margin of resected ileum. Set 1 (47 ileal CD, 27 UC, and 25 Control non-IBD patients) was used as the training set and Set 2 was subsequently collected as an independent test set (10 ileal CD, 10 UC, and 10 control non-IBD patients). We compared the 17 gene signatures selected by four different feature-selection methods to distinguish ileal CD phenotype with non-CD phenotype. The four methods yielded different but overlapping solutions that were highly discriminating. All four of these methods selected FOLH1 as a common feature. This gene is an established biomarker for prostate cancer, but has not previously been associated with Crohn's disease. Immunohistochemical staining confirmed increased expression of FOLH1 in the ileal epithelium. These results provide evidence for convergent molecular abnormalities in the macroscopically disease unaffected proximal margin of resected ileum from ileal CD subjects. PMID:22606341

  6. Chitosan-zinc chelate improves intestinal structure and mucosal function and decreases apoptosis in ileal mucosal epithelial cells in weaned pigs.

    PubMed

    Han, Xin-Yan; Ma, Yuan-Fei; Lv, Meng-Yuan; Wu, Zhi-Peng; Qian, Li-Chun

    2014-04-28

    The present study was conducted to investigate the effects of chitosan (CS)-Zn on intestinal morphology, mucosal epithelial cell apoptosis and mucosal immune function in weanling pigs. A total of 150 weanling barrows with a body weight of 7.2 kg were randomly allocated into five groups. A basal diet without Zn supplementation was used as the control and other four groups were fed the control diet supplemented with 50 or 100 mg/kg of Zn as CS-Zn, 100 mg/kg of Zn as ZnSO4 and 3000 mg/kg of Zn as ZnO, respectively. The feeding trial lasted for 28 d. The results showed that serum diamine oxidase activities, d-lactate levels and endotoxin contents were lower in pigs fed dietary 100 mg/kg of Zn as CS-Zn or 3000 mg/kg of Zn as ZnO than in pigs fed the control or 100 mg Zn/kg as ZnSO4 diet. The ratios of the villus height:crypt depth of the duodenum, jejunum and ileum were higher in pigs that received 100 mg/kg of Zn as CS-Zn or a high level of Zn as ZnO than in pigs fed the control diet. Moreover, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL)-stained ileal epithelial cells were found in the control group, and apoptotic cells did not appear prominently in pigs that received the 100 mg/kg of CS-Zn or ZnO diet. Secretory IgA concentration in ileal mucus was increased in the dietary group that received 100 mg/kg of CS-Zn or ZnO. These results indicated that dietary 100 mg CS-Zn/kg had similar biological effects to dietary 3000 mg ZnO/kg on intestinal morphology, mucosal epithelial cell apoptosis and mucosal immune function. PMID:24387792

  7. Glutathione

    PubMed Central

    Noctor, Graham; Queval, Guillaume; Mhamdi, Amna; Chaouch, Sejir; Foyer, Christine H.

    2011-01-01

    Glutathione is a simple sulfur compound composed of three amino acids and the major non-protein thiol in many organisms, including plants. The functions of glutathione are manifold but notably include redox-homeostatic buffering. Glutathione status is modulated by oxidants as well as by nutritional and other factors, and can influence protein structure and activity through changes in thiol-disulfide balance. For these reasons, glutathione is a transducer that integrates environmental information into the cellular network. While the mechanistic details of this function remain to be fully elucidated, accumulating evidence points to important roles for glutathione and glutathione-dependent proteins in phytohormone signaling and in defense against biotic stress. Work in Arabidopsis is beginning to identify the processes that govern glutathione status and that link it to signaling pathways. As well as providing an overview of the components that regulate glutathione homeostasis (synthesis, degradation, transport, and redox turnover), the present discussion considers the roles of this metabolite in physiological processes such as light signaling, cell death, and defense against microbial pathogen and herbivores. PMID:22303267

  8. Influence of source and micronization of soya bean meal on growth performance, nutrient digestibility and ileal mucosal morphology of Iberian piglets.

    PubMed

    Berrocoso, J D; Cámara, L; Rebollar, P G; Guzmán, P; Mateos, G G

    2014-04-01

    The effects of inclusion in the diet of different sources of soya bean meal (SBM) on growth performance, total tract apparent digestibility (TTAD) and apparent ileal digestibility (AID) of major dietary components and mucosal ileum morphology were studied in Iberian pigs weaned at 30 days of age. From 30 to 51 days of age (phase I), there was a control diet based on regular soya bean meal (R-SBM; 44% CP) of Argentina (ARG) origin and five extra diets in which a high-protein soya bean meal (HP-SBM; 49% CP) of the USA or ARG origin, either ground (990 ?m) or micronized (60 ?m), or a soya protein concentrate (SPC; 65% CP) substituted the R-SBM. From 51 to 61 days of age (phase II), all pigs were fed a common commercial diet in mash form. The following pre-planned orthogonal contrasts were conducted: (1) R-SBM v. all the other diets, (2) SPC v. all the HP-SBM diets, (3) micronized HP-SBM v. ground HP-SBM, (4) HP-SBM of ARG origin v. HP-SBM of US origin and (5) interaction between source and the degree of grinding of the HP-SBM. Dietary treatment did not affect growth performance of the pigs at any age but from 30 to 51 days of age, post weaning diarrhoea (PWD) was higher (P<0.001) and the TTAD and AID of all nutrients were lower for pigs fed the R-SBM diet than for pigs fed the HP-SBM or the SPC diets. However, no differences between the HP-SBM and the SPC containing diets were detected for any trait. The TTAD of organic matter (P=0.07) and gross energy (GE) (P=0.05) tended to be higher for the micronized HP-SBM than for the ground HP-SBM and that of GE was higher (P<0.05) for US meal than for the ARG meal. Pigs fed R-SBM had lower villus height (P<0.01) than pigs fed HP-SBM or SPC but no differences in ileal mucosal morphology were detected between SPC and HP-SBM containing diets. It is concluded that feeding the HP-SBM or SPC-reduced PWD and improved nutrient digestibility and ileal morphology as compared with feeding the R-SBM, but had no effect on pig performance. The inclusion in the diet of added value soya products (micronized SBM or SPC) in substitution of the R-SBM increased the TTAD of all nutrients and reduced PWD but had no advantage in terms of growth performance over the use of ground HP-SBM. PMID:24423429

  9. Effect of added zinc in diets with ractopamine hydrochloride on growth performance, carcass characteristics, and ileal mucosal inflammation mRNA expression of finishing pigs.

    PubMed

    Paulk, C B; Burnett, D D; Tokach, M D; Nelssen, J L; Dritz, S S; DeRouchey, J M; Goodband, R D; Hill, G M; Haydon, K D; Gonzalez, J M

    2015-01-01

    Two experiments were conducted to determine the effects of increasing the dietary Zn content on growth performance, carcass characteristics, plasma Zn, and ileal mucosal inflammation mRNA expression of finishing pigs fed diets containing ractopamine HCl (RAC; Elanco Animal Health, Greenfield, IN). In Exp. 1, 312 pigs (327 × 1050; PIC, Hendersonville, TN; 94 kg BW) were used in a 27-d study. There were 2 pigs per pen and 26 pens per treatment. Treatments included a corn-soybean meal diet (control; 0.66% standardized ileal digestible [SID] Lys); a diet (0.92% SID Lys) with 10 mg/kg RAC; and the RAC diet plus 50, 100, or 150 mg Zn/kg from ZnO or 50 mg Zn/kg from a Zn AA complex (ZnAA; Availa-Zn; Zinpro, Eden Prairie, MN). All diets also contained 83 mg Zn/kg from ZnSO4 in the trace mineral premix. Pigs fed the RAC diet without added Zn had increased (P < 0.05) ADG, G:F, HCW, carcass yield, and loin weight compared with pigs fed the control diet. Increasing Zn from ZnO in diets containing RAC tended to increase (linear, P = 0.067) G:F and loin weight (quadratic, P = 0.064). Pigs fed diets with 50 mg Zn/kg from ZnAA tended to have increased (P = 0.057) ADG compared with pigs fed the RAC diet. In Exp. 2, 320 pigs (327 × 1050; PIC; 98 kg BW) were used in a 35-d study. There were 2 pigs per pen and 20 pens per treatment. Treatments included a control diet (0.66% SID Lys); a diet (0.92% SID Lys) with 10 mg/kg RAC; or the RAC diet plus 75, 150, and 225 mg Zn/kg from ZnO or ZnAA. All diets also contained 55 mg Zn/kg from ZnSO4 from the trace mineral premix. Pigs fed the RAC diet had increased (P < 0.05) ADG, G:F, HCW, loin depth, percentage lean, and liver weight compared with pigs fed the control diet. No Zn level or source effects or level × source interactions were observed for growth performance. A Zn level × source interaction (quadratic, P = 0.007) was observed in liver Zn concentrations. This resulted from liver Zn concentrations plateauing at 150 mg Zn/kg when ZnO was supplemented, while there was a linear increase when using ZnAA. Increasing Zn in diets containing RAC increased (linear, P < 0.05) plasma Zn on d 18 and 32. The expression of IL-1? was increased (P = 0.014) in mucosa of pigs fed the RAC diet compared with those fed the control diet. Expression of IL-1? decreased (linear, P = 0.026) in the mucosa of pigs fed increasing added Zn. In conclusion, adding Zn to diets containing RAC resulted in a trend for improved growth performance of pigs in 1 of 2 experiments. Also, additional Zn increased plasma Zn and reduced IL-1?. PMID:25568367

  10. Impairment of intestinal mucosal antioxidant defense system during Salmonella typhimurium infection.

    PubMed

    Mehta, A; Singh, S; Ganguly, N K

    1998-03-01

    The mucosal pathology of Salmonella typhimurium infection may in part be due to the excessive production of reactive oxygen species (ROS). The influence of S. typhimurium infection on the intestinal mucosal antioxidant defense system was investigated. We injected ligated rat ileal loops with Salmonella live culture or toxin. After 18 hr of infection, the animals were killed and enterocytes isolated from the ileal loops. The enterocyte-reduced glutathione (GSH) content and activities of the enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase, glutathione-S-transferase (GST), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH) were spectrophotometrically estimated. The vitamin E and A contents were determined by high-performance liquid chromatography (HPLC). In both the Salmonella live culture and toxin-treated groups, the enterocyte GSH and vitamin E contents and activities of the enzymes SOD, GSH-Px, catalase, GR, and G6PDH were significantly decreased as compared to the control group. However there was a significant increase in the enterocyte activity of GST. There was no change in the vitamin A content of the enterocytes. These findings might indicate a decreased endogenous intestinal protection against ROS in S. typhimurium-mediated infection, which could contribute to the pathogenesis of the disease. PMID:9539663

  11. Neutrophil-derived oxidants mediate formyl-methionyl-leucyl-phenylalanine-induced increases in mucosal permeability in rats

    SciTech Connect

    von Ritter, C.; Grisham, M.B.; Hollwarth, M.; Inauen, W.; Granger, D.N. (Louisiana State Univ. Medical Center, Shreveport (USA))

    1989-09-01

    The effects of several free radical scavengers and antioxidant enzymes on neutrophil-mediated changes in mucosal permeability (measured using blood-to-lumen clearance of {sup 51}Cr-labeled ethylene-diaminetetraactate) were assessed using ileal loops perfused with N-formyl-methionyl-leucyl-phenylalanine (FMLP). Neither superoxide dismutase nor catalase reduced the FMLP-induced increase in mucosal permeability. However, manganese-loaded desferrioxamine (a superoxide dismutase mimetic), PZ51 (a glutathione peroxidase analogue), desferrioxamine (an iron chelator), or dimethylsulfoxide (a hydroxyl radical scavenger) significantly attenuated FMLP-induced mucosal damage. The results of our experiments indicate that neutrophilic oxidants are responsible for a major portion of the mucosal permeability changes induced by FMLP.

  12. Selenium-dependent glutathione peroxidase-GI is a major glutathione peroxidase activity in the mucosal epithelium of rodent intestine 1 Portions of this work were presented in the Selenium II minisymposia at Experimental Biology '96. Preliminary accounts of this work appear in the proceedings volumes of the Sixth International Symposium on Selenium in Biology and Medicine (ISSBM, 1996) and The Japanese Society of Chromatography (1996). 1

    Microsoft Academic Search

    R. Steven Esworthy; Kristine M. Swiderek; Ye-Shih Ho; Fong-Fong Chu

    1998-01-01

    Gpx2 mRNA, encoding a selenium-dependent glutathione peroxidase (GPX-GI), has been found to be highly expressed in the gastrointestinal tract (GI) mucosal epithelium. In this study, we show that GPX-GI is produced in the mucosal epithelium of the adult rat GI tract and that the activity levels are comparable to that from GPX-1. Post-mitochondrial supernatant GPX activity from the mucosal epithelium

  13. Total proctocolectomy and ileal - anal pouch

    MedlinePLUS

    Restorative proctocolectomy; Ileal-anal resection; Ileal-anal pouch; J-pouch; S-pouch; Pelvic pouch; Ileal-anal pouch; Ileal ... RD, Mahmoud N, Maron DJ, Ross HM, Rombeau J. Colon and rectum. In: Townsend CM, Beauchamp RD, ...

  14. Intestinal permeability in the ileal pouch.

    PubMed Central

    Merrett, M N; Soper, N; Mortensen, N; Jewell, D P

    1996-01-01

    BACKGROUND: Villous atrophy, mucin changes ('colonic metaplasia'), and chronic inflammation occur to varying degrees in all patients with ileal pouchanal anastomosis whereas acute inflammation (pouchitis) affects a subgroup of patients with prior ulcerative colitis. AIM: To measure epithelial barrier function looking for possible functional adaptation in ileal 'pouch' mucosa. PATIENTS: Patients with an ileal pouch prior to ileostomy closure (n = 12), functioning pouch (n = 14), pouchitis (n = 8), and ulcerative colitis (n = 12) were assessed. METHODS: 51Cr-EDTA was administered into the 'pouch' or rectum and urinary recovery over 24 hours was taken as an indication of permeability (barrier function). Histological analysis of 'pouch' biopsy specimens was undertaken. RESULTS: Mucosal permeability is decreased from median 9.4% (range 5.4% to 39.1%) to 1.4% (range 0.38% to 2.2%) after ileostomy closure (p < 0.002) with levels being negatively correlated with two histological parameters of colonic metaplasia-mucin changes (p = 0.03) and villous atrophy (p = 0.05). Pouchitis was associated with increased permeability 5.9% (1.9% to 19.5%) compared with healthy 'pouch' 1.4% (0.35 to 2.2%) (p < 0.006). CONCLUSION: Despite the presence of chronic inflammation in the mature 'pouch' functional adaptation with reduced permeability occurs in conjunction with colonic metaplasia. PMID:8991861

  15. Consequences of ileal pouch-anal anastomosis for Crohn's colitis

    Microsoft Academic Search

    Neil H. Hyman; Victor W. Fazio; Wayne B. Tuckson; Ian C. Lavery

    1991-01-01

    Patients with Crohn's colitis are generally not considered candidates for the ileal pouch-anal anastomosis (IPAA). procedure. We reviewed 362 consecutive patients undergoing IPAA and analyzed the outcome of this procedure on 25 patients with a preoperative diagnosis of mucosal ulcerative colitis who were subsequently proven to have Crohn's disease. The mean follow-up was 38.1 months. Sixteen patients have a functioning

  16. Ileal pouch surgery for ulcerative colitis

    PubMed Central

    Bach, Simon P; Mortensen, Neil J

    2007-01-01

    Ulcerative colitis (UC) is a relapsing and remitting disease characterised by chronic mucosal and submucosal inflammation of the colon and rectum. Treatment may vary depending upon the extent and severity of inflammation. Broadly speaking medical treatments aim to induce and then maintain remission. Surgery is indicated for inflammatory disease that is refractory to medical treatment or in cases of neoplastic transformation. Approximately 25% of patients with UC ultimately require colectomy. Ileal pouch-anal anastomosis (IPAA) has become the standard of care for patients with ulcerative colitis who ultimately require colectomy. This review will examine indications for IPAA, patient selection, technical aspects of surgery, management of complications and long term outcome following this procedure. PMID:17659667

  17. Ileal and colonic fatty acid profiles in patients with active Crohn's disease

    Microsoft Academic Search

    S Bühner; E Nagel; J Körber; H Vogelsang; T Linn; R Pichlmayr

    1994-01-01

    In patients with active Crohn's disease and in a control group the fatty acid profiles in the whole lipid fraction of ileal and colonic mucosal biopsy specimens were determined by capillary gas chromatography. The biopsy specimens in Crohn's disease patients were taken from the inflamed terminal ileum as well as from the inflamed and macroscopically normal colon. Compared with controls

  18. Construction of ileal reservoir with longitudinal ileal myotomy.

    PubMed

    Aly, A; Fonkalsrud, E W

    1988-08-01

    An attempt was made to construct an ileal reservoir in 15 colectomized dogs by making a longitudinal myotomy of 15 cm length. The volume of the myotomized ileal segment did not increase, even when accompanied by more than 50 per cent obstruction of the distal sigmoid colon for periods of follow-up to 4 months. Peristalsis was not altered by the longitudinal muscular incision on the antimesenteric side of the ileum. Although the operative technique for longitudinal ileal myotomy has the benefit of simplicity compared with construction of an ileal reservoir, the latter techniques, which have been used clinically on an extensive basis, are more likely to produce a consistent distension that is suitable for fecal storage. Although there were no leaks from the mucosa and no complications occurred in the 15 dogs evaluated, the dilatation of an isolated ileal segment was so minor that this technique appears to have little application in the treatment of patients undergoing the endorectal ileal pullthrough procedure. PMID:3395022

  19. Long-term histomorphological surveillance of the pelvic ileal pouch: Dysplasia develops in a subgroup of patients

    Microsoft Academic Search

    Béla Veress; Finn P. Reinholt; Kerstin Lindquist; Robert Löfberg; Lars Liljeqvist

    1995-01-01

    Background & Aims: Little is known about the longterm morphology of the pelvic ileal pouch after restorative proctocolectomy in patients with ulcerative colitis. This study analyzed the mucosal adaptation in the pouch during a long-term follow-up. Methods: Mucosal biopsy specimens were obtained from 87 patients during a follow-up of 6.3 years (SD, 2.7; range, 3–14 years). The villous surface density,

  20. Neurosecretory effect of ouabain on isolated rabbit ileal mucosa

    SciTech Connect

    Hubel, K.A.; Renquist, K.S.

    1988-01-01

    Ouabain, when added to fluid bathing rabbit ileal mucosa mounted in a flux chamber, transiently increases short circuit current, implying a paradoxical secretory response. To determine the cause of this change, the authors studied unidirectional fluxes of /sup 36/Cl and /sup 23/Na and the effects of ion substitution, of reduced Ca concentration, verapamil, tetrodotoxin and atropine. Ouabain 0.1 mM, transiently increased the serosal to mucosal flux of Cl and Na, increased Isc and PD and reduced ion conductance. The Isc response to ouabain was diminished by reducing the bath fluid concentration of CL, of Ca, and by adding verapamil. Tetrodotoxin both delayed and reduced the maximal Isc response; atropine had no effect. They conclude that ouabain acts by releasing a neurotransmitter of unknown identity and by increasing the serosal to mucosal flux to Cl.

  1. 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

  2. Inflammation Drives Dysbiosis and Bacterial Invasion in Murine Models of Ileal Crohn’s Disease

    PubMed Central

    Craven, Melanie; Egan, Charlotte E.; Dowd, Scot E.; McDonough, Sean P.; Dogan, Belgin; Denkers, Eric Y.; Bowman, Dwight; Scherl, Ellen J.; Simpson, Kenneth W.

    2012-01-01

    Background and Aims Understanding the interplay between genetic susceptibility, the microbiome, the environment and the immune system in Crohn’s Disease (CD) is essential for developing optimal therapeutic strategies. We sought to examine the dynamics of the relationship between inflammation, the ileal microbiome, and host genetics in murine models of ileitis. Methods We induced ileal inflammation of graded severity in C57BL6 mice by gavage with Toxoplasma gondii, Giardia muris, low dose indomethacin (LDI;0.1 mg/mouse), or high dose indomethacin (HDI;1 mg/mouse). The composition and spatial distribution of the mucosal microbiome was evaluated by 16S rDNA pyrosequencing and fluorescence in situ hybridization. Mucosal E. coli were enumerated by quantitative PCR, and characterized by phylogroup, genotype and pathotype. Results Moderate to severe ileitis induced by T. gondii (day 8) and HDI caused a consistent shift from >95% Gram + Firmicutes to >95% Gram - Proteobacteria. This was accompanied by reduced microbial diversity and mucosal invasion by adherent and invasive E. coli, mirroring the dysbiosis of ileal CD. In contrast, dysbiosis and bacterial invasion did not develop in mice with mild ileitis induced by Giardia muris. Superimposition of genetic susceptibility and T. Gondii infection revealed greatest dysbiosis and bacterial invasion in the CD-susceptible genotype, NOD2?/?, and reduced dysbiosis in ileitis-resistant CCR2?/? mice. Abrogating inflammation with the CD therapeutic anti-TNF-?-mAb tempered dysbiosis and bacterial invasion. Conclusions Acute ileitis induces dysbiosis and proliferation of mucosally invasive E. coli, irrespective of trigger and genotype. The identification of CCR2 as a target for therapeutic intervention, and discovery that host genotype and therapeutic blockade of inflammation impact the threshold and extent of ileal dysbiosis are of high relevance to developing effective therapies for CD. PMID:22848538

  3. Risk Factors and True Incidence of Pouchitis in Patients after Ileal Pouch–Anal Anastomoses

    Microsoft Academic Search

    Erik J. Simchuk; Richard C. Thirlby

    2000-01-01

    .   Total colectomy, mucosal proctectomy, and ileal J pouch–anal anastomosis (IPAA) has become the procedure of choice for patients\\u000a with ulcerative colitis and familial adenomatous polyposis. The purpose of this study was to determine the short- and long-term\\u000a outcomes of patients undergoing IPAA by a single surgeon, correlating intraoperative technical aspects with outcomes, and\\u000a to characterize better the clinical syndrome

  4. Enhanced production of IL-8 in chronic but not in early ileal lesions of Crohn's disease (CD)

    PubMed Central

    Brandt, E; Colombel, J-F; Ectors, N; Gambiez, L; Emilie, D; Geboes, K; Capron, M; Desreumaux, P

    2000-01-01

    Distinct Th1/Th2 patterns have been observed during the evolution of CD. The aim of this study was to compare neutrophil involvement and IL-8 mRNA and protein expression during early recurrent lesions and chronic phases of CD. Twenty-nine patients with CD having ileocolonic resection with anastomosis were studied. Biopsies were obtained during surgery from the non-inflamed ileal mucosa and from chronic ileal lesions. Endoscopic ileal biopsies were also taken from early recurrent ileal lesions occurring 3 months after surgery. Neutrophil counts were performed and mucosal IL-8 levels were evaluated by competitive reverse transcriptase-polymerase chain reaction and immunohistochemistry. Early recurrent ileal lesions were characterized by low neutrophil counts and IL-8 production at the mRNA and protein levels compared with the ileal chronic lesions. The main cellular sources of IL-8 in the early recurrent lesions were neutrophils, while in chronic lesions the majority of IL-8-stained cells were CD3+ T cells and macrophages. These results confirmed that the nature of the inflammatory infiltrate and the expression of cytokine profiles may differ between the acute and chronic phases of CD. PMID:11091272

  5. Mucosal immunity and vaccines

    Microsoft Academic Search

    Cecil Czerkinsky; Jan Holmgren

    2005-01-01

    There is currently great interest in developing mucosal vaccines against a variety of microbial pathogens. Mucosally induced tolerance also seems to be a promising form of immunomodulation for treating certain autoimmune diseases and allergies. Here we review the properties of the mucosal immune system and discuss advances in the development of mucosal vaccines for protection against infections and for treatment

  6. Low ileal interleukin 10 concentrations are predictive of endoscopic recurrence in patients with Crohn's disease

    PubMed Central

    Meresse, B; Rutgeerts, P; Malchow, H; Dubucquoi, S; Dessaint, J P; Cohard, M; Colombel, J F; Desreumaux, P

    2002-01-01

    Background: Endoscopic recurrence after surgery in Crohn's disease is frequent and unpredictable. Abnormal intestinal production of pro- (interleukin (IL)-1?, tumour necrosis factor ? (TNF-?)) and anti- (IL-10) inflammatory cytokines has been associated with severe outcome in experimental models of colitis. Patients and methods: We evaluated if ileal TNF-?, IL-1?, or IL-10 mRNA levels measured at the time of surgery predict endoscopic recurrence, and if ileal IL-10 levels are associated with particular IL-10 promoter alleles. Ileal biopsies were obtained peroperatively from the healthy neoileum of patients undergoing a right ileocolectomy for Crohn's disease. Mucosal TNF-?, IL-1?, and IL-10 mRNA levels were quantified by competitive polymerase chain reaction. A cut off value was determined using a receiver operating curve. IL-10.G promoter haplotypes were analysed using a polymorphic dinucleotide repeat in the IL-10 promoter region. Results: Three months after surgery, 53% of patients had endoscopic recurrence while 47% remained free of disease. The risk of endoscopic recurrence correlated with ileal IL-10 mRNA concentrations (r2=0.81). Endoscopic recurrence occurred more frequently in patients classified as low IL-10 producers than in those that were high producers (80% v 40%) (p=0.02). Patients with at least one of the two alleles G7–8 or G10–13 produced, respectively, higher (p=0.006) and lower (p=0.029) ileal IL-10 mRNA. The distribution of IL-10.G microsatellite genotypes was similar in patients with or without endoscopic recurrence. Conclusion: Low ileal IL-10 mRNA concentration is a good marker of endoscopic recurrence in Crohn's disease but the distribution of IL-10.G haplotypes cannot predict the postoperative evolution of the disease. PMID:11772962

  7. [Continent replacement enterocystoplasty using a low-pressure detubularized ileal pouch after radical prostatocystectomy].

    PubMed

    Boccon-Gibod, L; Leleu, C; Peyret, C; Conquy, S

    1988-01-01

    Tubular ileal-ileo-caecal or colonic replacement enterocystoplasties induce nocturnal incontinence in more than 70% of cases, partly due to the presence of peristaltic waves responsible for pressures greater than 40 cm of water for low filling volumes. The use of debutularised intestinal grafts considerably attenuates these pressure waves, ensuring excellent diurnal continence and a dramatic reduction in nocturnal incontinence together with protection of the upper urinary tract. The detubularised ileal bladder combines the reliability of all low pressure reservoirs with a simple technique: a 30 cm ileal segment is isolated then opened 2 cm from its anti-mesenteric border. The two limbs of the loop are sutured to each other. The ureters are reimplanted at the summit of each limb according to the mucosal groove procedure and the summit of the pouch is anastomosed to the urethra. This procedure has been used in 10 patients following radical cystectomy for cancer. Seven of these patients underwent clinical, radiological and urodynamic examination 5 months after the operation: all 7 patients were continent during the day. Nocturnal continence was obtained at the cost of getting up one or twice during the night, but incontinence persisted in the other 3 patients. Cystometry did not reveal any pressure waves greater than 25 cm of water for a volume of 500 ml. The detubularised ileal bladder is simple to perform and constitutes a reasonable alternative to traditional tubular enterocystoplasties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3369843

  8. Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity

    PubMed Central

    2013-01-01

    Background Mitrella kentii (M. kentii) (Bl.) Miq, is a tree-climbing liana that belongs to the family Annonaceae. The plant is rich with isoquinoline alkaloids, terpenylated dihydrochalcones and benzoic acids and has been reported to possess anti-inflammatory activity. The purpose of this study is to assess the gastroprotective effects of desmosdumotin C (DES), a new isolated bioactive compound from M. kentii, on gastric ulcer models in rats. Methods DES was isolated from the bark of M. kentii. Experimental rats were orally pretreated with 5, 10 and 20 mg/kg of the isolated compound and were subsequently subjected to absolute ethanol-induced acute gastric ulcer. Gross evaluation, mucus content, gastric acidity and histological gastric lesions were assessed in vivo. The effects of DES on the anti-oxidant system, non-protein sulfhydryl (NP-SH) content, nitric oxide (NO)level, cyclooxygenase-2 (COX-2) enzyme activity, bcl-2-associated X (Bax) protein expression and Helicabacter pylori (H pylori) were also investigated. Results DES pre-treatment at the administered doses significantly attenuated ethanol-induced gastric ulcer; this was observed by decreased gastric ulcer area, reduced or absence of edema and leucocytes infiltration compared to the ulcer control group. It was found that DES maintained glutathione (GSH) level, decreased malondialdehyde (MDA) level, increased NP-SH content and NO level and inhibited COX-2 activity. The compound up regulated heat shock protein-70 (HSP-70) and down regulated Bax protein expression in the ulcerated tissue. DES showed interesting anti-H pylori effects. The efficacy of DES was accomplished safely without any signs of toxicity. Conclusions The current study reveals that DES demonstrated gastroprotective effects which could be attributed to its antioxidant effect, activation of HSP-70 protein, intervention with COX-2 inflammatory pathway and potent anti H pylori effect. PMID:23866830

  9. Ulcer associated cell lineage glands expressing trefoil peptide genes are induced by chronic ulceration in ileal pouch mucosa

    PubMed Central

    Pera, M; Heppell, J; Poulsom, R; Teixeira, F; Williams, J

    2001-01-01

    BACKGROUND—Chronic ulcerative conditions in the gastrointestinal tract result in the appearance of the ulcer associated cell lineage (UACL). The glands of this new cell lineage secrete epidermal growth factor, transforming growth factor ?, and the trefoil factor family (TFF) peptides, which are known to participate in repair processes. Pouchitis is the most frequent complication of ileal pouch-anal anastomosis.?AIM—Our aim was to determine whether the mucosal ulceration present in pouchitis can induce the development of UACL glands.?METHODS—Biopsies from ileal pouches with pouchitis (n=10), healthy pouches (n=5), and normal terminal ileum (n=5) were studied. Expression of TFF mRNA was assessed by in situ hybridisation. TFF1 and TFF2 proteins were localised by immunochemistry.?RESULTS—UACL glands containing TFF1 and TFF2 were observed in six patients with pouchitis. In some glands, there was TFF3 mRNA as has been reported for Crohn's UACL. None of the biopsies from ileal reservoirs without pouchitis showed UACL glands (p<0.05). Neither TFF1 nor TFF2 expression was detected in ileal reservoirs without pouchitis.?CONCLUSION—UACL glands arise de novo in ileal pouch mucosa of patients with pouchitis and express all three TFF peptide genes. Chronic inflammation alone, present in healthy pouches, is not enough to stimulate the growth of the UACL, and additional stimuli consequent on ulceration may be needed.???Keywords: ulcer associated cell lineage; trefoil peptides; chronic ulceration; pouchitis PMID:11358897

  10. Alterations in Ileal Mucosa Bacteria Related to Diet Complexity and Growth Performance in Young Pigs

    PubMed Central

    Levesque, Crystal L.; Hooda, Seema; Swanson, Kelly S.; de Lange, Kees

    2014-01-01

    Background Evaluation of the prolonged impact of weaning diet on ileal mucosa bacteria and during periods of reduced and improved growth was conducted using 454 pyrosequencing. Methodology/Principal Findings Weaned pigs were fed HIGH or LOW complexity diets, with or without antibiotics, for 6 weeks, followed by a common grower diet. Pigs were killed at 2 (n?=?4 or 5) and 8 (n?=?6) weeks post-weaning (periods of reduced and improved growth, respectively). Mucosal bacteria were removed; DNA was extracted and amplified using the V1–V3 region of the 16S rRNA gene. Mucosal bacteria clustered more closely by week post-weaning than diet but 44% of bacterial species did not change from week 2 to 8. There was no effect of diet complexity or antibiotic inclusion on indices of bacterial diversity. Firmicutes made up 91 and 96% of total reads at week 2 and 8, respectively. The proportion of Clostridium paraputrificum increased (P?=?0.003) from week 2 to 8 in pigs fed LOW but didn’t change in pigs fed HIGH; whereas Clostridium leptum decreased (P?=?0.02) from week 2 to 8 in pigs fed LOW but didn’t change in pigs fed HIGH. The proportion of Sarcina genus was 3-fold higher in pigs fed A+ compared to A? at week 2 and 5-fold higher at week 8 despite the lack of in-feed antibiotics at that time. Conclusions/Significance Shifts in mucosal bacteria populations may be related to dietary induced changes in growth performance during reduced and improved growth but further studies are required to confirm causative relationship. Weaning diet results in species specific prolonged alterations in mucosal bacteria, particularly where high levels of in-feed antibiotics are used. A considerable portion of ileal mucosal bacteria colonize early and remain stable over time despite changes in diet. PMID:25247930

  11. Mucosal dendritic cells shape mucosal immunity

    PubMed Central

    Chang, Sun-Young; Ko, Hyun-Jeong; Kweon, Mi-Na

    2014-01-01

    Dendritic cells (DCs) are key modulators that shape the immune system. In mucosal tissues, DCs act as surveillance systems to sense infection and also function as professional antigen-presenting cells that stimulate the differentiation of naive T and B cells. On the basis of their molecular expression, DCs can be divided into several subsets with unique functions. In this review, we focus on intestinal DC subsets and their function in bridging the innate signaling and adaptive immune systems to maintain the homeostasis of the intestinal immune environment. We also review the current strategies for manipulating mucosal DCs for the development of efficient mucosal vaccines to protect against infectious diseases. PMID:24626170

  12. ["T antireflux mechanism" Ileal neobladder].

    PubMed

    González, Javier; Angulo, Javier

    2011-04-01

    During the past 15 years, orthotopic urinary diversion surgery has evolved from "experimental"to become the standard treatment in higher volume and experience world centers as the preferred method of urinary diversion in both sexes. The overall complication rate of the intussuscepted afferent segment required for the construction of a continent Koch reservoir, led to the late 90's development and description by Skinner et al. of the continence and anti-reflux "T- mechanism". Based on the subserosal appendix-tunneling described by Mitrofanoff and the extraserosal ureteric-tunnelling by Ghoneim, this new mechanism has been used successfully incorporated into an orthotopic diversion system ("T-neobladder or T-pouch"). Apparently, this "T-mechanism"has eliminated the problems associated with the intussuscepted intestinal segment, while maintaining an effective anti-reflux and continence system. This article describes in detail the surgical steps for the construction of an ileal T-neobladder. PMID:21498889

  13. GLUTATHIONE SYNTHESIS

    PubMed Central

    Lu, Shelly C.

    2012-01-01

    BACKGROUND Glutathione (GSH) is present in all mammalian tissues as the most abundant non-protein thiol that defends against oxidative stress. GSH is also a key determinant of redox signaling, vital in detoxification of xenobiotics, regulates cell proliferation, apoptosis, immune function, and fibrogenesis. Biosynthesis of GSH occurs in the cytosol in a tightly regulated manner. Key determinants of GSH synthesis are the availability of the sulfur amino acid precursor, cysteine, and the activity of the rate-limiting enzyme, glutamate cysteine ligase (GCL), which is composed of a catalytic (GCLC) and a modifier (GCLM) subunit. The second enzyme of GSH synthesis is GSH synthetase (GS). SCOPE OF REVIEW This review summarizes key functions of GSH and focuses on factors that regulate the biosynthesis of GSH, including pathological conditions where GSH synthesis is dysregulated. MAJOR CONCLUSIONS GCL subunits and GS are regulated at multiple levels and often in a coordinated manner. Key transcription factors that regulate the expression of these genes include NF-E2 related factor 2 (Nrf2) via the antioxidant response element (ARE), AP-1, and nuclear factor kappa B (NF?B). There is increasing evidence that dysregulation of GSH synthesis contributes to the pathogenesis of many pathological conditions. These include diabetes mellitus, pulmonary and liver fibrosis, alcoholic liver disease, cholestatic liver injury, endotoxemia and drug-resistant tumor cells. GENERAL SIGNIFICANCE GSH is a key antioxidant that also modulates diverse cellular processes. A better understanding of how its synthesis is regulated and dysregulated in disease states may lead to improvement in the treatment of these disorders. PMID:22995213

  14. The S ileal pouch-anal anastomosis

    Microsoft Academic Search

    Carol-Ann Vasilevsky; David A. Rothenberger; Stanley M. Goldberg

    1987-01-01

    In order to determine the results with the S ileal pouch-anal anastomosis, 116 consecutive patients who had undergone total abdominal colectomy with rectal mucosectomy and endorectal ileal pouch-anal anastomosis were assessed following ileostomy closure. In 11 patients (9.5%) pouch removal and\\/or conversion to permanent ileostomy was necessary because of Crohn's disease (3), pelvic sepsis (3), pouchitis (2), incontinence (2), or

  15. THE T POUCH: AN ORTHOTOPIC ILEAL NEOBLADDER INCORPORATING A SEROSAL LINED ILEAL ANTIREFLUX TECHNIQUE

    Microsoft Academic Search

    JOHN P. STEIN; GARY LIESKOVSKY; DAVID A. GINSBERG; BERNARD H. BOCHNER; DONALD G. SKINNER

    1998-01-01

    PurposeAt our institution the Kock ileal neobladder has been the primary form of urinary diversion after cystectomy. The few associated complications are primarily related to the intussuscepted antireflux afferent limb, including stones, stenosis and extussusception of the afferent nipple. We present a novel orthotopic ileal neobladder, the T pouch, with an innovative antireflux technique designed to prevent complications of the

  16. Host Responses to Persistent Mycobacterium avium Subspecies paratuberculosis Infection in Surgically Isolated Bovine Ileal Segments

    PubMed Central

    Charavaryamath, Chandrashekhar; Gonzalez-Cano, Patricia; Fries, Patrick; Gomis, Susantha; Doig, Kimberley; Scruten, Erin; Potter, Andrew; Napper, Scott

    2013-01-01

    A lack of appropriate disease models has limited our understanding of the pathogenesis of persistent enteric infections with Mycobacterium avium subsp. paratuberculosis. A model was developed for the controlled delivery of a defined dose of M. avium subsp. paratuberculosis to surgically isolated ileal segments in newborn calves. The stable intestinal segments enabled the characterization of host responses to persistent M. avium subsp. paratuberculosis infections after a 9-month period, including an analysis of local mucosal immune responses relative to an adjacent uninfected intestinal compartment. M. avium subsp. paratuberculosis remained localized at the initial site of intestinal infection and was not detected by PCR in the mesenteric lymph node. M. avium subsp. paratuberculosis-specific T cell proliferative responses included both CD4 and ?? T cell receptor (??TcR) T cell responses in the draining mesenteric lymph node. The levels of CD8+ and ??TcR+ T cells increased significantly (P < 0.05) in the lamina propria, and M. avium subsp. paratuberculosis-specific tumor necrosis factor alpha (TNF-?) and gamma interferon secretion by lamina propria leukocytes was also significantly (P < 0.05) increased. There was a significant (P < 0.05) accumulation of macrophages and dendritic cells (DCs) in the lamina propria, but the expression of mucosal toll-like receptors 1 through 10 was not significantly changed by M. avium subsp. paratuberculosis infection. In conclusion, surgically isolated ileal segments provided a model system for the establishment of a persistent and localized enteric M. avium subsp. paratuberculosis infection in cattle and facilitated the analysis of M. avium subsp. paratuberculosis-specific changes in mucosal leukocyte phenotype and function. The accumulation of DC subpopulations in the lamina propria suggests that further investigation of mucosal DCs may provide insight into host responses to M. avium subsp. paratuberculosis infection and improve vaccine strategies to prevent M. avium subsp. paratuberculosis infection. PMID:23221000

  17. Radiation induced oral mucositis.

    PubMed

    Ps, Satheesh Kumar; Balan, Anita; Sankar, Arun; Bose, Tinky

    2009-07-01

    PATIENTS RECEIVING RADIOTHERAPY OR CHEMOTHERAPY WILL RECEIVE SOME DEGREE OF ORAL MUCOSITIS THE INCIDENCE OF ORAL MUCOSITIS WAS ESPECIALLY HIGH IN PATIENTS: (i) With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii) who also received concomitant chemotherapy; (iii) who received a total dose over 5,000 cGy; and (iv) who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene. PMID:20668585

  18. Mucosal immune response in cattle with subclinical Johne's disease.

    PubMed

    Weiss, D J; Evanson, O A; Souza, C D

    2006-03-01

    Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's disease, a chronic granulomatous enteritis of wild and domestic ruminants. During a long subclinical period, the organism persists in the intestine despite systemic cellular and humoral immune responses. To explore the mucosal immune response in Johne's disease, we isolated mononuclear leukocytes from the ileum of cows naturally infected with M. avium subsp. paratuberculosis and from cows that were not infected. We evaluated the immunophenotype of these cells and the proliferative responses after the addition of M. avium subsp. paratuberculosis sonicate or B-cell or T-cell mitogens. Although the percentage of T cells was increased in infected cows, these cells consisted mostly of memory (CD2+CD62L-) and regulatory (CD4+CD25+) T cells. Further evidence of immune hyporesponsiveness included a decrease in the percentage of T cells with an activated phenotype and a decrease in cells expressing major histocompatibility factor class II (MHC class II). Unlike the spleen, ileal lymphocytes from infected cows failed to proliferate in response to M. avium subsp. paratuberculosis sonicate. Additionally, ileal lymphocytes from infected cows proliferated poorly in response to concanavalin A and pokeweed mitogen, suggesting generalized T cell and B cell hyporesponsiveness. These results indicate that a state of tolerance may exist in the intestine of cows subclinically infected with M. avium subsp. paratuberculosis organisms in subclinically infected cows. This effect may be induced, at least in part, by proliferation of regulatory T cells that nonspecifically suppress mucosal immune responsiveness. PMID:16537930

  19. Volvulus of ileal S-pouch: A rare complication of ileal pouch anal anastomoses

    PubMed Central

    Tyagi, Gaurav; Gupta, Utsav; Verma, Ankit; Saxena, Dhananjay; Mittal, Atul; Goyal, Amit; Kankaria, Jeevan; Jenaw, R.K.

    2014-01-01

    INTRODUCTION Ileal pouch anal anastomosis (IPAA) after total proctocolectomy is a frequently performed surgery for medically refractory ulcerative colitis (UC). Volvulus of the ileal pouch as a complication of IPAA is extremely rare. We present a case of volvulus of S-type ileal pouch. PRESENTATION OF CASE A 28 year old male, with history of total proctocolectomy with IPAA for severe UC in 2009 presented with signs of bowel obstruction. Emergency laparotomy was done and a volvulus of the S-type ileal pouch was derotated and pouchpexy done. DISCUSSION The IPAA has a wide spectrum of complications, with obstruction of proximal small bowel occurring frequently. Volvulus of the ileal pouch is extremely rare with only 3 reported cases. Early diagnosis and intervention is important to salvage the pouch. Computed tomography (CT) may aid the diagnosis in stable patients. CONCLUSION The diagnosis of ileal pouch volvulus although rare, should be kept in mind when dealing with patients complaining of recurrent obstruction following IPAA. PMID:25212904

  20. Male issues of the ileal pouch.

    PubMed

    Kani, Haluk T; Shen, Bo

    2015-03-01

    : Restorative proctocolectomy with ileal pouch-anal anastomosis is the standard surgical treatment modality for patients with ulcerative colitis who require colectomy. There are special issues related to male gender. We performed systemic literature review on the topic, incorporating the experience in our specialized Center for Ileal Pouch Disorders, and provide recommendations for the identification and management for the gender-specific issues in male patients with ileal pouches. Chronic pouchitis, particularly ischemic pouchitis, anastomotic leak, and presacral sinus are more common in male patients than their female counterparts. Sexual dysfunction can occur after pouch surgery, particularly in those with pouch failure. Diagnosis and management of benign and malignant prostate diseases can be challenging due to the altered pelvic anatomy from the surgery. Digital rectal examination for prostate cancer screening is not reliable. Transpouch biopsy of prostate may lead to pouch fistula or abscess. Pelvic radiation therapy may have an adverse impact on the pouch function. In conclusion, sexual dysfunction and enlarged prostate can occur in patients with the ileal pouch. The measurement of serum prostate-specific antigen is a preferred method for the screening of prostate cancer. If biopsy of the prostate is needed, the perineal route is recommended. The risk for pouch dysfunction and the benefit for oncologic survival of pelvic radiation for prostate cancer should be carefully balanced. PMID:25437820

  1. 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. PMID:24451793

  2. Glutathione Production in Yeast

    NASA Astrophysics Data System (ADS)

    Bachhawat, Anand K.; Ganguli, Dwaipayan; Kaur, Jaspreet; Kasturia, Neha; Thakur, Anil; Kaur, Hardeep; Kumar, Akhilesh; Yadav, Amit

    Glutathione, ? -glutamyl-cysteinyl-glycine, is the most abundant non-protein thiol found in almost all eukaryotic cells (and in some prokaryotes). The tripeptide, which is synthesized non-ribosomally by the consecutive action of two soluble enzymes, is needed for carrying out numerous functions in the cell, most important of which is the maintenance of the redox buffer. The cycle of glutathione biosynthesis and degradation forms part of the ? -glutamyl cycle in most organisms although the latter half of the pathway has not been demonstrated in yeasts. Our current understanding of how glutathione levels are controlled at different levels in the cell is described. Several different routes and processes have been attempted to increase commercial production of glutathione using both yeast and bacteria. In this article we discuss the history of glutathione production in yeast. The current bottlenecks for increased glutathione production are presented based on our current understanding of the regulation of glutathione homeostasis, and possible strategies for overcoming these limitations for further enhancing and improving glutathione production are discussed

  3. Ileal pouch-anal anastomosis without ileostomy

    Microsoft Academic Search

    Susan Galandiuk; Bruce G. Wolff; Roger R. Dozois; Robert W. Beart

    1991-01-01

    Thirty-seven patients underwent construction of a J-ileal pouch-anal anastomosis (IPAA) without temporary diverting ileostomy for chronic ulcerative colitis (CUC) (20 patients), familial adenomatous polyposis (FAP) (15 patients), indeterminate colitis (1 patient) and nonhereditary polyposis coli (1 patient) between 1981 and 1990. Seven of 20 CUC patients (35 percent) were on steroids at the time of hospital admission. The postoperative course

  4. Hydroxystearic acid and diarrhoea following ileal resection

    PubMed Central

    Wiggins, H. S.; Cummings, J. H.; Pearson, Joy R.

    1974-01-01

    The faecal outputs of 10 patients who complained of diarrhoea after ileal resection were measured whilst they consumed identical diets in which most of the fat was present as olive oil. No relationship was found between faecal weight and hydroxystearic acid production. In three patients the output of hydroxystearic acid was reduced by changing the dietary fat. There was no reduction in faecal weight. It is concluded that hydroxystearic acid does not contribute to diarrhoea in these cases. PMID:18668849

  5. Effect of the route of administration on the mucosal and systemic immune responses to Lawsonia intracellularis vaccine in pigs.

    PubMed

    Nogueira, M G; Collins, A M; Dunlop, R H; Emery, D

    2015-04-01

    In an on-farm study, 40 weaned piglets aged 3 weeks were vaccinated with Lawsonia intracellularis vaccine orally, IM or IP while a fourth group remained unvaccinated. All vaccinated animals showed increased serum levels of L. intracellularis-specific IgG antibodies, but significantly elevated concentrations of specific IgG, IgA and cytokines were generated in ileal mucosal secretions from the orally and IP vaccinated pigs when examined at 17 days after vaccination. PMID:25817978

  6. Stress-related mucosal disease

    Microsoft Academic Search

    Mitchell J. Spirt

    2003-01-01

    Opinion statement  Stress-related mucosal disease (SRMD) includes stress-related injury (superficial mucosal damage) and stress ulcers (focal\\u000a deep mucosal damage). Both types are caused by mucosal ischemia, and both show a propensity for the acid-producing corpus\\u000a and fundus. Prophylaxis of stress ulcers may reduce major bleeding but, so far, has not been shown to improve survival. The\\u000a most widely used drugs for

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

    PubMed Central

    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.

    2014-01-01

    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. PMID:25003194

  8. 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. PMID:25003194

  9. Selenium-enriched Agaricus bisporus mushroom protects against increase in gut permeability ex vivo and up-regulates glutathione peroxidase 1 and 2 in hyperthermally-induced oxidative stress in rats.

    PubMed

    Maseko, Tebo; Dunshea, Frank Rowland; Howell, Kate; Cho, Hyun-Jung; Rivera, Leni Rose; Furness, John Barton; Ng, Ken

    2014-06-01

    Dietary effects of organic Se supplementation in the form of Se-enriched Agaricus bisporus mushroom on ileal mucosal permeability and antioxidant selenoenzymes status in heat induced oxidative stress in rats were evaluated. Acute heat stress (40 °C, 21% relative humidity, 90 min exposure) increased ileum baseline short circuit current (Isc; 2.40-fold) and epithelial conductance (Ge; 2.74-fold). Dietary supplementation with Se-enriched A. bisporus (1 µg Se/g feed) reduced (p < 0.05) ileum Isc and Ge during heat stress to 1.74 and 1.91 fold, respectively, indicating protection from heat stress-induced mucosal permeability increase. The expression of ileum glutathione peroxidase (GPx-) 1 and 2 mRNAs were up-regulated (p < 0.05) by 1.90 and 1.87-fold, respectively, for non-heat stress rats on the Se-enriched diet relative to the control. The interplay between heat stress and dietary Se is complex. For rats on the control diet, heat stress alone increased ileum expression of GPx-1 (2.33-fold) and GPx-2 (2.23-fold) relative to thermoneutral conditions. For rats on the Se-enriched diet, heat stress increased (p < 0.05) GPx-1 expression only. Rats on Se-enriched + ?-tocopherol diet exhibited increased expression of both genes (p < 0.05). Thus, dietary Se-enriched A. bisporus protected against increase in ileum permeability and up-regulated GPx-1 and GPx-2 expression, selenoenzymes relevant to mitigating oxidative stress. PMID:24962481

  10. Selenium-Enriched Agaricus bisporus Mushroom Protects against Increase in Gut Permeability ex vivo and Up-Regulates Glutathione Peroxidase 1 and 2 in Hyperthermally-Induced Oxidative Stress in Rats

    PubMed Central

    Maseko, Tebo; Dunshea, Frank Rowland; Howell, Kate; Cho, Hyun-Jung; Rivera, Leni Rose; Furness, John Barton; Ng, Ken

    2014-01-01

    Dietary effects of organic Se supplementation in the form of Se-enriched Agaricus bisporus mushroom on ileal mucosal permeability and antioxidant selenoenzymes status in heat induced oxidative stress in rats were evaluated. Acute heat stress (40 °C, 21% relative humidity, 90 min exposure) increased ileum baseline short circuit current (Isc; 2.40-fold) and epithelial conductance (Ge; 2.74-fold). Dietary supplementation with Se-enriched A. bisporus (1 µg Se/g feed) reduced (p < 0.05) ileum Isc and Ge during heat stress to 1.74 and 1.91 fold, respectively, indicating protection from heat stress-induced mucosal permeability increase. The expression of ileum glutathione peroxidase (GPx-) 1 and 2 mRNAs were up-regulated (p < 0.05) by 1.90 and 1.87-fold, respectively, for non-heat stress rats on the Se-enriched diet relative to the control. The interplay between heat stress and dietary Se is complex. For rats on the control diet, heat stress alone increased ileum expression of GPx-1 (2.33-fold) and GPx-2 (2.23-fold) relative to thermoneutral conditions. For rats on the Se-enriched diet, heat stress increased (p < 0.05) GPx-1 expression only. Rats on Se-enriched + ?-tocopherol diet exhibited increased expression of both genes (p < 0.05). Thus, dietary Se-enriched A. bisporus protected against increase in ileum permeability and up-regulated GPx-1 and GPx-2 expression, selenoenzymes relevant to mitigating oxidative stress. PMID:24962481

  11. The ileal brake--inhibition of jejunal motility after ileal fat perfusion in man

    Microsoft Academic Search

    R C Spiller; I F Trotman; B E Higgins; M A Ghatei; G K Grimble; Y C Lee; S R Bloom; J J Misiewicz; D B Silk

    1984-01-01

    The possibility that malabsorbed fat passing through the human ileum exerts an inhibitory feedback control on jejunal motility has been investigated in 24 normal subjects by perfusing the ileum with a fat containing solution designed to produce ileal luminal fat concentrations similar to those in steatorrhoea (30-40 mg\\/ml). Mean transit times through a 30 cm saline perfused jejunal segment were

  12. Original article Ileal true digestibility of amino acids

    E-print Network

    Paris-Sud XI, Université de

    Original article Ileal true digestibility of amino acids in wheat milling by-products for pigs (WF), 3 of wheat bran (WB) ­ were analysed and studied for their protein and amino acid ileal true the least digestible amino acids, whereas methionine was among the most digestible ones. N and all amino

  13. Neuroregulation of Mucosal Vasculature

    Microsoft Academic Search

    Alfredo Chetta; Giovanna Pisi; Dario Olivieri

    The profuse microvasculature, present in the airway mucosa, can play a key role in normal homeostasis as well as in airway\\u000a inflammation. An intricate network of efferent and afferent autonomic nerves regulate the mucosal airway vessels. The nerve\\/vessel\\u000a interplay is complex and not yet completely clarified. In response to inspired air conditions, the sensory nerves can recruit\\u000a appropriate reflexes, which

  14. Stimulation of bile acid active transport related to increased mucosal cyclic AMP content in rat ileum in vitro.

    PubMed

    Reymann, A; Braun, W; Drobik, C; Woermann, C

    1989-05-10

    The regulation of bile acid transport in rat ileum was studied in vitro using the adenylate cyclase stimulator forskolin, or 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor. Forskolin 20 microM as well as 100 microM IBMX enhanced mucosal cyclic AMP to 3-fold the control levels. As a physiological response, net fluid absorption in everted ileal sacs was reduced. Taurocholate (10-500 microM) transfer in everted perfused segments of rat ileum was measured using a three compartment dual label method suitable for measuring active transport. Transport asymmetry with absorption exceeding its counterflux by 26-fold, was measured at 500 microM taurocholate. Forskolin increased absorption of taurocholate still further, by 68%, and reduced the serosal to mucosal flux. Enhanced intracellular accumulation of taurocholate indicated a stimulatory action of forskolin on active transport at the mucosal brush-border membrane. In uptake studies, accumulation of taurocholate was enhanced by 100 microM IBMX also. Forskolin-induced uptake stimulation could also be shown for chenodeoxycholate and cholate. In the presence of the neuronal blocker tetrodotoxin, uptake stimulation was still effective. Results indicate that the ileal bile acid transporter is included within the group of sodium-dependent cotransporters of the rat small intestine which are subject to a cyclic AMP-related stimulation at the mucosal cellular level. PMID:2469477

  15. INTERACTION OF HALOACETONITRILES WITH GLUTATHIONE AND GLUTATHIONE-S-TRANSFERASE

    EPA Science Inventory

    The interactions of reduced glutathione (GSH) with haloacetonitriles (HAH) were carried out under various conditions and the depletion of GSH was determined. Haloacetonitriles reacted directly with glutathione in the absence of tissue extracts. he reactivities of haloacetonitrile...

  16. Direct binding studies on ileal and cardiac muscarinic receptors.

    PubMed Central

    Michel, A. D.; Whiting, R. L.

    1987-01-01

    1 Functional studies have indicated that muscarinic receptors in cardiac tissue differ from those in the ileum. In the present study ileal and cardiac muscarinic receptors identified by [3H]-N-methyl scopolamine ([3H]-NMS) were characterized and the selectivity of currently available ileal and atrial selective antagonists determined. 2 In terms of the current functional classification of muscarinic receptors both ileal and cardiac muscarinic receptors were of the M2 subtype based upon their low affinity for pirenzepine. 3 Cyclohexylphenyl(2-piperidinoethyl)silanol (CPPS), a highly ileal selective antagonist in functional studies, was unable to distinguish between ileal and atrial muscarinic receptors identified in binding studies. Furthermore, although AF-DX 116 and dicyclomine were able to differentiate atrial and ileal muscarinic receptors, neither compound was more than 2 fold selective. These data indicate that it is not possible to subclassify ileal and atrial muscarinic receptors using direct ligand binding studies with these antagonists. 4 In circular ileal smooth muscle, apparent heterogeneity of the M2 muscarinic receptor population was observed. Thus AF-DX 116 identified two populations of sites with affinities differing by 30 fold. These two populations of M2 muscarinic receptors may represent the typical M2 muscarinic receptors identified in cardiac tissue and the more recently discovered 'gland type' M2 muscarinic receptors. 5 The circular ileal smooth muscle tissue homogenate was able to decrease dramatically the apparent affinity of adiphenine. This activity, which appeared to result from a phenylmethylsulphonylfluoride (PMSF) sensitive protease effect, should be considered when conducting studies using this tissue preparation and compounds of similar structure to adiphenine. PMID:3427279

  17. The glutathione peroxidases

    Microsoft Academic Search

    J. R. Arthur

    2000-01-01

    There are several proteins in mammalian cells that can metabolize hydrogen peroxide and lipid hydroperoxides. These proteins include four selenium-containing glutathione peroxidases that are found in different cell fractions and tissues of the body. This review considers the structure and distribution of the selenoperoxidases and how this relates to their biological function. The functions of the selenoperoxidases were originally studied

  18. 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

  19. Ileal pouch-anal anastomosis without temporary, diverting ileostomy

    Microsoft Academic Search

    Amanda M. Metcalf; Roger R. Dozois; Keith A. Kelly; Bruce G. Wolff

    1986-01-01

    Of two hundred patients undergoing proctocolectomy with ileal pouch-anal anastomosis, all but nine have had temporary diverting\\u000a ileostomies. Of these nine patients, eight had successful results. One patient developed abdominal sepsis due to jejunal volvulus\\u000a and perforation after she had returned home, and at surgery the pouch was excised. Ileal pouch-anal anastomosis without a\\u000a temporary diverting ileostomy can be performed

  20. Duodenal Chemosensing and Mucosal Defenses

    PubMed Central

    Akiba, Yasutada; Kaunitz, Jonathan D.

    2011-01-01

    The duodenal mucosa is exposed to endogenous and exogenous chemicals, including acid, CO2, bile acids and nutrients. Mucosal chemical sensors are necessary to exert physiological responses such as secretion, digestion, absorption, and motility. We propose a mucosal chemosensing system by which luminal chemicals are sensed via mucosal acid sensors and G-protein-coupled receptors. Luminal acid/CO2 sensing consists of ecto- and cytosolic carbonic anhydrases, epithelial ion transporters, and acid sensors expressed on the afferent nerves in the duodenum. Furthermore, a luminal L-glutamate signal is mediated via mucosal L-glutamate receptors, including metabotropic glutamate receptors and taste receptor 1 family heterodimers, with activation of afferent nerves and cyclooxygenase, whereas luminal Ca2+ is differently sensed via the calcium-sensing receptor in the duodenum. Recent studies also show the involvement of enteroendocrine G-protein-coupled receptors in bile acid and fatty acid sensing in the duodenum. These luminal chemosensors help activate mucosal defense mechanisms in or- der to maintain the mucosal integrity and physiological responses. Stimulation of luminal chemosensing in the duodenal mucosa may prevent mucosal injury, affect nutrient metabolism, and modulate sensory nerve activity. PMID:21389725

  1. New advances in mucosal vaccination.

    PubMed

    Ranasinghe, Charani

    2014-10-01

    The ICI 2013 Mucosal Vaccine Workshop presentations covered a wide range of topics, these mainly fell into three categories: (i) Understanding the interactions of host and microbes, specifically commensal pathogens and improving the antigen uptake via the (microfold cells) M cells to induce effective IgA antibody immunity at the gut mucosa; (ii) effective plant-based vaccines and (iii) development of prophylactic and therapeutic mucosal-based vaccine strategies for virus infections such as human immunodeficiency virus (HIV), influenza and human papillomavirus (HPV) associated head and neck cancers. How to improve the efficacy of oral vaccines, novel intranasal mucosal adjuvants and a unique intra-cheek delivery method were also discussed. Presenters emphasized the differences associated with systemic and mucosal vaccination, specifically, how mucosal vaccines unlike systemic delivery can induce effective immunity at the first line of defence. Collectively, the workshop provided insights into recent developments in the mucosal vaccine research field, highlighting the complexities associated with designing safe and effective mucosal vaccines. PMID:24462961

  2. Mucosal immunology of geohelminth infections in humans

    Microsoft Academic Search

    P J Cooper

    2009-01-01

    There is limited data on the human mucosal immune response to geohelminths, but extensive data from experimental animals. Geohelminth infections may modulate mucosal immunity with effects on parasite expulsion or persistence and mucosal inflammation. Geohelminths are considered to have important effects on immunity to mucosal vaccines, infectious disease susceptibility, and anti-inflammatory effects in inflammatory bowel disease and asthma. This review

  3. Evidence for validity of ileal digestibility coefficients in monogastrics.

    PubMed

    Columbus, Daniel; de Lange, Cornelis F M

    2012-08-01

    Measures of amino acid (AA) digestibility are used widely to estimate bioavailability of AA in feed and food ingredients for monogastric animals. In principle, the digestibility assay is simpler than in vivo assessments of AA bioavailability and allows for simultaneous estimation of the bioavailability of all AA in an experimental diet. It is generally assumed that absorption of intact AA in the hindgut of monogastrics is minimal, even though colonocytes do contain AA transporters and have been shown to absorb AA. This assumption is supported by the observation that infusion of AA into the hindgut does not improve nitrogen balance in monogastrics. In addition, growth performance of monogastrics is more highly correlated with ileal than faecal AA digestibility. Therefore, ileal digestibility coefficients provide better estimates of AA bioavailability than faecal digestibility coefficients. Measures of apparent ileal digestibility (AID) of AA are confounded with endogenous gut AA losses (EAAL). The curvilinear increase in AID of AA with increasing dietary AA level has been attributed to the relatively large contribution of EAAL to total ileal AA flows at low dietary AA levels. Subtracting basal EAAL from total ileal AA flows yields standardized ileal digestibility (SID) coefficients that appear to be more additive than AID coefficients in mixtures of feed ingredients. An implicit assumption when using SID AA coefficients in diet formulation is that the post-absorptive utilization of AA is not influenced by the dietary protein source. This assumption appears inappropriate when using feed or food ingredients that have been over-heated, induce large amounts of EAAL, or contain substantial amounts of fermentable fibre. Improved understanding of processes that contribute to the discrepancy between bioavailability and ileal digestibility will allow a more effective use of AA digestibility coefficients in diet formulation. PMID:23107537

  4. Functions of glutathione and glutathione disulfide in immunology and immunopathology

    Microsoft Academic Search

    KLAUS SCHULZE-OSTHOFF; SABINE MIHM; DAGMAR GALTER; HEIKE SCHENK; HANS-PETER ECK; STEFFEN ROTH; HELMUT GMUNDER

    Even a moderate increase in the cellular cysteine supply elevates the intracellular glutathione (GSH) and glutathione disulfide (GSSG) levels and poten- tiates immunological functions of lymphocytes in vitro. At low GSSG levels, T cells cannot optimally activate the im- munologically important transcription factor NFxB, whereas high GSSG levels inhibit the DNA binding ac- tivity of NFxB. The effects of GSSG

  5. CD83+CCR7- dendritic cells accumulate in the subepithelial dome and internalize translocated Escherichia coli HB101 in the Peyer's patches of ileal Crohn's disease.

    PubMed

    Salim, Sa'ad Y; Silva, Manuel A; Keita, Asa V; Larsson, Marie; Andersson, Peter; Magnusson, Karl-Eric; Perdue, Mary H; Söderholm, Johan D

    2009-01-01

    Recurrent Crohn's disease originates with small erosions in the follicle-associated epithelium overlying the Peyer's patches. Animal studies have illustrated mucosal immune regulation by dendritic cells located in the subepithelial dome. The aim of this study was to characterize the dendritic cells at this specific site in patients with Crohn's disease. Ileal tissues were obtained after surgery performed on Crohn's patients; ileal samples from noninflammatory bowel disease and ulcerative colitis served as standard and inflammatory controls, respectively. Flow cytometry of isolated intestinal mononuclear cells showed a larger subset of dendritic cells in Crohn's samples compared with controls. This finding was corroborated by confocal microscopy, showing enhanced infiltrates of cells positive for the dendritic cell markers, DC-SIGN(+) and CD83(+), in the subepithelial dome. Moreover, the CD83(+) cells in Crohn's tissues showed reduced expression of the lymph node migratory receptor, CCR7, possibly contributing to the high numbers of dendritic cells. After exposure to nonpathogenic Escherichia coli in Ussing chambers, dendritic cells in the subepithelial dome of Crohn's disease demonstrated increased co-localization with translocated bacteria. Immunohistochemical results revealed that DC-SIGN(+) cells in Crohn's tissues were found to express toll-like receptor 4 and produce tumor necrosis factor-alpha. In conclusion, nonmigrating dendritic cells that accumulate in the subepithelial dome and internalize nonpathogenic bacteria may be important for the onset and perpetuation of mucosal inflammation in Crohn's disease. PMID:19095953

  6. Genetics Home Reference: Glutathione synthetase deficiency

    MedlinePLUS

    ... disorder that prevents the production of an important molecule called glutathione. Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production. Glutathione also plays a ...

  7. Multiphasic analysis of the temporal development of the distal gut microbiota in patients following ileal pouch anal anastomosis

    PubMed Central

    2013-01-01

    Background The indigenous gut microbiota are thought to play a crucial role in the development and maintenance of the abnormal inflammatory responses that are the hallmark of inflammatory bowel disease. Direct tests of the role of the gut microbiome in these disorders are typically limited by the fact that sampling of the microbiota generally occurs once disease has become manifest. This limitation could potentially be circumvented by studying patients who undergo total proctocolectomy with ileal pouch anal anastomosis (IPAA) for the definitive treatment of ulcerative colitis. A subset of patients who undergo IPAA develops an inflammatory condition known as pouchitis, which is thought to mirror the pathogenesis of ulcerative colitis. Following the development of the microbiome of the pouch would allow characterization of the microbial community that predates the development of overt disease. Results We monitored the development of the pouch microbiota in four patients who underwent IPAA. Mucosal and luminal samples were obtained prior to takedown of the diverting ileostomy and compared to samples obtained 2, 4 and 8 weeks after intestinal continuity had been restored. Through the combined analysis of 16S rRNA-encoding gene amplicons, targeted 16S amplification and microbial cultivation, we observed major changes in structure and function of the pouch microbiota following ileostomy. There is a relative increase in anaerobic microorganisms with the capacity for fermentation of complex carbohydrates, which corresponds to the physical stasis of intestinal contents in the ileal pouch. Compared to the microbiome structure encountered in the colonic mucosa of healthy individuals, the pouch microbial community in three of the four individuals was quite distinct. In the fourth patient, a community that was much like that seen in a healthy colon was established, and this patient also had the most benign clinical course of the four patients, without the development of pouchitis 2 years after IPAA. Conclusions The microbiota that inhabit the ileal-anal pouch of patients who undergo IPAA for treatment of ulcerative colitis demonstrate significant structural and functional changes related to the restoration of fecal flow. Our preliminary results suggest once the pouch has assumed the physiologic role previously played by the intact colon, the precise structure and function of the pouch microbiome, relative to a normal colonic microbiota, will determine if there is establishment of a stable, healthy mucosal environment or the reinitiation of the pathogenic cascade that results in intestinal inflammation. PMID:24451366

  8. [Two cases of severe variceal haemorrhage from an ileal conduit.

    PubMed

    Lunden, Dagmar; Poulsen, Johan; Kloster, Brian O

    2014-09-22

    Variceal haemorrhage from an ileal conduit is a rare but well-known complication to portal hypertension. Many treatments are described and a transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice if possible, because this addresses the underlying portal hypertension. We report two cases of haemorrhage from an ileal conduit, which illustrates that treatment must be individualized with attention to life expectancy, co-morbidities and degree of the portosystemic pressure gradient, but TIPS treatment has to be considered even if there is no history of liver disease. PMID:25294334

  9. Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats.

    PubMed

    Strader, April D; Vahl, Torsten P; Jandacek, Ronald J; Woods, Stephen C; D'Alessio, David A; Seeley, Randy J

    2005-02-01

    Bariatric surgeries, such as gastric bypass, result in dramatic and sustained weight loss that is usually attributed to a combination of gastric volume restriction and intestinal malabsorption. However, studies parceling out the contribution of enhanced intestinal stimulation in the absence of these two mechanisms have received little attention. Previous studies have demonstrated that patients who received intestinal bypass or Roux-en-Y surgery have increased release of gastrointestinal hormones. One possible mechanism for this increase is the rapid transit of nutrients into the intestine after eating. To determine whether there is increased secretion of anorectic peptides produced in the distal small intestine when this portion of the gut is given greater exposure to nutrients, we preformed ileal transpositions (IT) in rats. In this procedure, an isolated segment of ileum is transposed to the jejunum, resulting in an intestinal tract of normal length but an alteration in the normal distribution of endocrine cells along the gut. Rats with IT lost more weight (P < 0.05) and consumed less food (P < 0.05) than control rats with intestinal transections and reanastomosis without transposition. Weight loss in the IT rats was not due to malabsorption of nutrients. However, transposition of distal gut to a proximal location caused increased synthesis and release of the anorectic ileal hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY; P < 0.01). The association of weight loss with increased release of GLP-1 and PYY suggests that procedures that promote gastrointestinal endocrine function can reduce energy intake. These findings support the importance of evaluating the contribution of gastrointestinal hormones to the weight loss seen with bariatric surgery. PMID:15454396

  10. Effect of type of grinding of barley and dehydrated alfalfa on performance, digestion, and crude mucin ileal concentration in growing rabbits.

    PubMed

    Romero, C; Nicodemus, N; Rodríguez, J D; García, A I; de Blas, C

    2011-08-01

    The effects of type of grinding of barley and dehydrated alfalfa (DA) were tested in rabbits weaned at 35 d of age with an average BW of 846 ± 93 g. Four nonmedicated diets were arranged in a 2 × 2 factorial structure, with type of grinding (coarse grinding with a 4.5-mm screen or fine grinding with a 1.5-mm screen) of barley (TGB) and DA (TGDA) as the main factors. A total of 1,056 mixed-sex rabbits (264 per diet) were fattened until d 63. Most of these rabbits (216 per diet) were housed in pairs and were used only to record mortality rate. Mortality was also recorded for the remaining 192 rabbits, which were housed individually and used to determine growth performance. From this group, 100 rabbits were used to determine digestive traits. Apart from those rabbits, a different group of 88 rabbits (44 housed individually and the remaining 44 housed in pairs) was used in the digestibility trial. All rabbits in this group were used to determine ileal digestibility (13 pools of ileal digesta per diet) and ileal mucin concentration (6 pools of ileal digesta per diet), whereas only the 44 individually housed rabbits were used to assess the fecal digestibility coefficients (11 rabbits per diet). Last, a jejunal sample was excised from 32 of the 44 individually housed rabbits to determine mucosal histology. Treatments did not affect ADG, ADFI, or G:F in the entire fattening period, but in the 49- to 63-d period, the diet containing both finely ground barley and DA reduced ADFI (P=0.08) compared with the other treatments (130 vs. 137 g). Moreover, this diet increased total digestive tract (4.76%, P=0.08) and cecal content (11.3%, P=0.08) weights compared with the other 3 treatments. Pylorus (P=0.09) and mixed digesta (P=0.06) pH, respectively, were reduced from 1.53 and 1.59 to 1.37 and 1.44 when both barley and DA were finely instead of coarsely ground. Grinding both barley and DA coarsely reduced the ileal digestibility of starch (0.899 vs. 0.936, P=0.06), increased (P < 0.01) its ileal flow and content in the feces to 1.66 g/d and 7.42 g/kg of DM, respectively, and led to decreased fecal digestibility (0.932 vs. 0.951, P < 0.01) compared with fine grinding. Coarse DA shortened villi (612 vs. 704 ?m, P=0.02), increased crypt depth (121 vs. 92.1 ?m, P=0.01), and reduced the villus:crypt ratio (5.08 vs. 7.66, P < 0.01) compared with finely ground DA. Furthermore, the greatest ileal crude mucin (148 vs. 107 g/kg of DMI, P=0.02) and sialic acid (71.7 vs. 61.7 mg/kg of DMI, P=0.04) concentrations were reported in rabbits receiving the diet with both coarsely ground barley and DA. Finally, mortality rate was not influenced by treatments, with an average of 9.64%. In conclusion, the diet containing finely ground barley and coarsely ground DA did not increase the weight of cecal contents, resulting in increased feed intake and leading to increased ileal digestibility and reduced ileal flow of starch. PMID:21478455

  11. 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

  12. Intestinal mucosal tolerance and impact of gut microbiota to mucosal tolerance

    PubMed Central

    Chistiakov, Dimitry A.; Bobryshev, Yuri V.; Kozarov, Emil; Sobenin, Igor A.; Orekhov, Alexander N.

    2015-01-01

    The mucosal barriers are very sensitive to pathogenic infection, thereby assuming the capacity of the mucosal immune system to induce protective immunity to harmful antigens and tolerance against harmless substances. This review provides current information about mechanisms of induction of mucosal tolerance and about impact of gut microbiota to mucosal tolerance. PMID:25628617

  13. Ileal pouch\\/anal anastomosis for Crohn's disease

    Microsoft Academic Search

    Y Panis; B Poupard; P Hautefeuille; P Valleur; J Nemeth; A Lavergne

    1996-01-01

    SummaryBackground Patients with Crohn's disease (CD) are not commonly considered as candidates for ileal pouch\\/anal anastomosis (IPAA). This approach has been avoided because of the poor results observed, retrospectively, in patients with an initial diagnosis of ulcerative colitis who were found to have CD on examination of the resected specimen. However, in 1985, we decided to investigate an alternative to

  14. Intracorporeal ileal ureter replacement using laparoscopy and robotics

    PubMed Central

    Sim, Allen; Todenhöfer, Tilman; Mischinger, Johannes; Halalsheh, Omar; Boettge, Johannes; Rausch, Steffen; Bier, Simone; Aufderklamm, Stefan; Stenzl, Arnulf; Gakis, Georgios

    2014-01-01

    Introduction Ileal ureter is a suitable treatment option for patients with long ureteric strictures. Minimally invasive techniques have been shown to be as safe as open techniques but superior in terms of post–operative recovery. We report our experience using minimally invasive techniques for total intracorporeal ureteral replacement. Material and methods A chart review revealed five patients who underwent intracorporeal ileal ureter using minimally invasive techniques in the preceding 5 years. 4 patients underwent conventional laparoscopic surgery and 1 patient underwent robotic–assisted surgery. Patient's characteristics, perioperative data and functional outcomes as well as a detailed description of surgical technique are reported. In all 5 of these patients, the ileal ureter was performed completely intracorporeally. Results The median age of our patients is 61 (range 42–73). The median operative time was 250 minutes (range 150–320) and median blood loss was 100 ml (range 50–200). The median hospital stay was 8 days (range 6–10) and there were no major perioperative complications reported. At median follow up of 22 months (range 4–38), there were no recurrences of strictures or any other complications. Conclusions We have demonstrated the safety and feasibility of minimally invasive intracorporeal ileal ureter. Numbers are still small but its application is likely to grow further. PMID:25667767

  15. Mucosal protective effects of vitamin E and misoprostol during acute radiation-induced enteritis in rats.

    PubMed

    Empey, L R; Papp, J D; Jewell, L D; Fedorak, R N

    1992-02-01

    Cytotoxic effects of ionizing radiation on gastrointestinal epithelium may be mediated by oxygen free radicals. Therapeutic intervention directed toward oxidant scavenging and increasing tissue oxygen tension may provide a novel approach to management. We investigated the effects of a nonenzymatic oxygen radical scavenger (vitamin E) and an exogenous PGE1 analog known to increase mucosal blood flow (misoprostol) on acute radiation enteritis. Rats were pretreated with: (1) vitamin E, (2) misoprostol, or (3) a combination of both agents prior to 10 Gy abdominal radiation. Three days following irradiation, net fluid absorption using in vivo isolated loops, mucosal histology, and mucosal morphometry using a computerized videoplan were determined in jejunum, ileum, and colon. Nonirradiated control intestine demonstrated net fluid absorption in all segments, which was not altered by vitamin E and/or misoprostol treatment. Irradiation significantly reduced net fluid absorption in jejunum, ileum, and colon. Vitamin E administered prior to irradiation maintained jejunal, ileal, and colonic fluid absorption near control levels. In contrast misoprostol or a combination of vitamin E and misoprostol did not provide protection against the injury caused by abdominal irradiation. Alterations in intestinal fluid absorption occurred without significant changes in histologic or morphometric appearance. In conclusion, ionizing radiation reduces in vivo intestinal fluid absorption without significant changes in histologic or morphometric appearance. Treatment with vitamin E, but not misoprostol, protects gastrointestinal mucosa against radiation-induced absorptive injury. PMID:1735337

  16. Immunology of gut mucosal vaccines.

    PubMed

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

    2011-01-01

    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

  17. Mucosal immunity and the microbiome.

    PubMed

    Neish, Andrew S

    2014-01-01

    By definition, the mucosal immune system is responsible for interfacing with the outside world, specifically responding to external threats, of which pathogenic microbes represent a primary challenge. However, it has become apparent that the human host possesses a numerically vast and taxonomically diverse resident microbiota, predominantly in the gut, and also in the airway, genitourinary tract, and skin. The microbiota is generally considered symbiotic, and has been implicated in the regulation of cellular growth, restitution after injury, maintenance of barrier function, and importantly, in the induction, development, and modulation of immune responses. The mucosal immune system uses diverse mechanisms that protect the host from overt pathogens, but necessarily has coevolved to monitor, nurture, and exploit the normal microbiota. As a whole, mucosal immunity encompasses adaptive immune regulation that can involve systemic processes, local tissue-based innate and inflammatory events, intrinsic defenses, and highly conserved cell autonomous cytoprotective responses. Interestingly, specific taxa within the normal microbiota have been implicated in roles shaping specific adaptive, innate, and cell autonomous responses. Taken together, the normal microbiota exerts profound effects on the mucosal immune system, and likely plays key roles in human physiology and disease. PMID:24437401

  18. Comparison of inhibitory effects between acetaminophen-glutathione conjugate and reduced glutathione in human glutathione reductase.

    PubMed

    Nýdlová, Erika; Vrbová, Martina; Cesla, Petr; Jankovi?ová, Barbora; Ventura, Karel; Roušar, Tomáš

    2014-09-01

    Acetaminophen overdose is the most frequent cause of acute liver injury. The main mechanism of acetaminophen toxicity has been attributed to oxidation of acetaminophen. The oxidation product is very reactive and reacts with glutathione generating acetaminophen-glutathione conjugate (APAP-SG). Although this conjugate has been recognized to be generally nontoxic, we have found recently that APAP-SG could produce a toxic effect. Therefore, the aim of our study was to estimate the toxicity of purified APAP-SG by characterizing the inhibitory effect in human glutathione reductase (GR) and comparing that to the inhibitory effect of the natural inhibitor reduced glutathione. We used two types of human GR: recombinant and freshly purified from red blood cells. Our results show that GR was significantly inhibited in the presence of both APAP-SG and reduced glutathione. For example, the enzyme activity of recombinant and purified GR was reduced in the presence of 4?mm APAP-SG (with 0.5?mm glutathione disulfide) by 28% and 22%, respectively. The type of enzyme inhibition was observed to be competitive in the cases of both APAP-SG and glutathione. As glutathione inhibits GR activity in cells under physiological conditions, the rate of enzyme inhibition ought to be weaker in the case of glutathione depletion that is typical of acetaminophen overdose. Notably, however, enzyme activity likely remains inhibited due to the presence of APAP-SG, which might enhance the pro-oxidative status in the cell. We conclude that our finding could reflect some other pathological mechanism that may contribute to the toxicity of acetaminophen. PMID:24038001

  19. Glutathione and mitochondria

    PubMed Central

    Ribas, Vicent; García-Ruiz, Carmen; Fernández-Checa, José C.

    2014-01-01

    Glutathione (GSH) is the main non-protein thiol in cells whose functions are dependent on the redox-active thiol of its cysteine moiety that serves as a cofactor for a number of antioxidant and detoxifying enzymes. While synthesized exclusively in the cytosol from its constituent amino acids, GSH is distributed in different compartments, including mitochondria where its concentration in the matrix equals that of the cytosol. This feature and its negative charge at physiological pH imply the existence of specific carriers to import GSH from the cytosol to the mitochondrial matrix, where it plays a key role in defense against respiration-induced reactive oxygen species and in the detoxification of lipid hydroperoxides and electrophiles. Moreover, as mitochondria play a central strategic role in the activation and mode of cell death, mitochondrial GSH has been shown to critically regulate the level of sensitization to secondary hits that induce mitochondrial membrane permeabilization and release of proteins confined in the intermembrane space that once in the cytosol engage the molecular machinery of cell death. In this review, we summarize recent data on the regulation of mitochondrial GSH and its role in cell death and prevalent human diseases, such as cancer, fatty liver disease, and Alzheimer’s disease. PMID:25024695

  20. Glutathione analogues in cancer treatment

    Microsoft Academic Search

    David Hamilton; Gerald Batist

    2004-01-01

    Glutathione is an important intracellular antioxidant and redox potential regulator that plays a vital role in drug detoxification\\u000a and elimination and in cellular protection from damage by free radicals, peroxides, and toxins. Molecular alterations reported\\u000a in many of the components of the glutathione system in various tumors and cancer cell lines can lead to increased survival\\u000a and enhanced chemotherapy drug

  1. Peroxynitrite inhibits glutathione S-conjugate transport.

    PubMed

    Soszy?ski, M; Bartosz, G

    1997-04-01

    Peroxynitrite was demonstrated to inhibit the active efflux of glutathione S-conjugates (2,4-dinitrophenyl-S-glutathione and bimane-S-glutathione) from human erythrocytes and the erythrocyte membrane ATPase activity stimulated by glutathione S-conjugates. As the multidrug resistance-associated protein (MRP) is responsible for the transport of glutathione S-conjugates in mammalian cells, these results point to the possibility of the effect of peroxynitrite on the MRP function. PMID:9106491

  2. Antiretroviral Pharmacology in Mucosal Tissues

    PubMed Central

    Thompson, Corbin G.; Cohen, Myron S.; Kashuba, Angela D.M.

    2014-01-01

    Strategies to prevent HIV infection using pre-exposure prophylaxis (PrEP) are required to curtail the HIV pandemic. The mucosal tissues of the genital and rectal tracts play a critical role in HIV acquisition, but antiretroviral (ARV) disposition and correlates of efficacy within these tissues are not well understood. Pre-clinical and clinical strategies to describe ARV pharmacokinetic-pharmacodynamic relationships (PK/PD) within mucosal tissues are currently being investigated. In this review, we summarize the physiochemical and biologic factors influencing ARV tissue exposure. Further, we discuss the necessary steps to generate relevant PK/PD data and the challenges associated with this process. Finally, we suggest how pre-clinical and clinical data might be practically translated into optimal PrEP dosing strategies for clinical trials testing using mathematical modeling and simulation. PMID:23764642

  3. 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

  4. Ileal intussusception due to a parasite egg: A case report

    PubMed Central

    Pinto, José Pedro; Cordeiro, Agostinho; Ferreira, Ana Margarida; Antunes, Conceição; Botelho, Patrícia; Rodrigues, Ana João; Leão, Pedro

    2014-01-01

    Ileal intussusception is the invagination of the small intestine within itself and accounts for 1% of cases of acute obstruction. However, physicians do not initially consider intussusception as a possible diagnosis of obstruction due to its rarity in adults. Herein, we report the case of a 22-year-old male who was admitted to the Emergency Department with continuous abdominal pain. Ultrasonography and computed tomography revealed an ileal intussusception. The patient underwent surgical removal of the segment of the small bowel. Unexpectedly, pathology revealed that the invagination occurred due to a parasite egg, with features suggestive of Schistosoma species. Schistosomiasis, although considered a parasitic disease in tropical countries, is not absent from Europe and though it is highly improbable, it may be responsible for cases of intussusception in adults. PMID:25278716

  5. Effect of Ileal Bypass and Alfalfa on Hypercholesterolaemia

    PubMed Central

    Barichello, A. W.; Fedoroff, S.

    1971-01-01

    Experiments are described which were designed to find out how alfalfa prevents hypercholesterolaemia in rabbits. It was found that rabbits with shortened small intestine (ileal bypass) required less alfalfa to prevent blood serum cholesterol elevation than rabbits with normal length of gut and that rabbits with ileal bypass absorbed less cholesterol than normal rabbits. It was found that rabbits receiving 600 mg. of cholesterol daily required more alfalfa than those receiving 300 mg. to prevent hypercholesterolaemia. The lower amount of alfalfa required to prevent a rise in the blood serum cholesterol in rabbits with shortened small intestine could be due to decreased ability to absorb cholesterol from the intestinal lumen. The observation that more alfalfa was required to prevent a blood serum cholesterol rise when rabbits received higher doses of cholesterol tends to support the hypothesis that alfalfa prevents hypercholesterolaemia by forming unabsorbable complexes with cholesterol in the intestinal lumen. PMID:5547660

  6. Dietary habits after ileal pouch-anal anastomosis.

    PubMed

    Chartrand-Lefebvre, C; Heppell, J; Davignon, I; Dubé, S; Pomp, A

    1990-04-01

    Dietary habits of patients who had undergone ileal pouch-anal anastomosis were assessed and correlated with bowel function. Twenty-four well-adapted patients (11 women, 13 men; mean age 32 years) voluntarily entered the study 30 +/- 4 months after closure of the diverting ileostomy. A standardized questionnaire on 108 food items and a 3-day food journal were used in the assessment. Twenty-one patients had no difficulty in selecting an appropriate diet. Caloric intake was adequate. Specific symptoms associated with several foods were as follows: increased stool frequency (beer, spirits, chinese food), decreased stool consistency (beer, wine, fried fish), perianal irritation (spicy foods), undigested particles (grapefruit, lettuce), odours (eggs). Pasta and bananas were associated with increased stool consistency. The authors believe that these observations may help in dietary counselling after ileal pouch-anal anastomosis. PMID:2268807

  7. Cytomegalovirus Enteritis Causing Ileal Perforation in an Elderly Immunocompetent Individual

    PubMed Central

    Lee, Joung Il; Choe, Jae Won; Joo, Kwang Ro; Jung, Sung Won; Shin, Hyun Phil; Choi, Sung Il

    2010-01-01

    Cytomegalovirus (CMV) infection is usually subclinical in immunocompetent individuals, however it can be life threatening in an elderly immunocompetent individual. We report a case of CMV enteritis causing ileal perforation in a physically active elderly man. An 88-year-old healthy man presented with abdominal pain and diarrhea. After initial conservative treatment, emergency laparotomy was performed for ileal perforation. The diagnosis of CMV enteritis was based on histological findings revealing many large cells with CMV inclusion bodies in the surgical specimen. In elderly individuals, even though they are immunocompetent, CMV enteritis may result in major complications such as bowel perforation, and it should be included in the differential diagnosis of diarrhea if it is resistant to conventional treatment. PMID:20191024

  8. Primary ileal villous atrophy is often associated with microscopic colitis

    PubMed Central

    Marteau, P; Lavergne-Slove, A; Lemann, M; Bouhnik, Y; Bertheau, P; Becheur, H; Galian, A; Rambaud, J

    1997-01-01

    Three cases of apparent primary villous atrophy of the terminal ileum in women with chronic diarrhoea are reported. Eight cases have previously been reported in the literature. Clinical characteristics are the presence of severe chronic secretory diarrhoea with episodes of hypokalaemia combined with signs of ileal malabsorption and/or efficacy of cholestyramine. Diagnosis is based on ileoscopy and histology. An association with microscopic colitis was present in the three patients and in four cases in the literature. The pathogenesis of primary ileal villous atrophy remains unknown and may involve dysimmunity. Its association with microscopic colitis may indicate a common pathogenesis or support the hypothesis that the faecal stream or bile salts play a role in the pathogenesis of microscopic colitis. ?? Keywords: intestinal villous atrophy; ileum; secretory diarrhoea; bile acid malabsorption; microscopic colitis PMID:9391260

  9. 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. PMID:16227213

  10. Temporary ileostomy for ileal pouch-anal anastomosis

    Microsoft Academic Search

    Amanda M. Metcalf; Roger R. Dozois; Robert W. Beart; Ketth A. Kelly; Bruce G. Wolff

    1986-01-01

    The function and complications associated with temporary ileostomies were reviewed in patients undergoing ileal pouch-anal\\u000a anastomosis. A series of 180 patients had temporary ileostomies established (157 loop, 23 Brooke). Patients with incomplete\\u000a fecal diversion had a significantly higher incidence of pouch-anal anastomotic complications (44 percent) than did those with\\u000a complete diversion (14 percent). Patients with loop ileostomies were more likely

  11. Ileal pouch vaginal fistulas: Incidence, etiology, and management

    Microsoft Academic Search

    Steven D. Wexner; David A. Rothenberger; Linda Jensen; Stanley M. Goldberg; Emmanuel G. Balcos; Paul Belliveau; Bradley H. Bennett; John G. Buls; Jeffrey M. Cohen; Harold L. Kennedy; Steven J. Medwell; Theodore M. Ross; David J. Schoetz; Lee E. Smith; Alan G. Thorson

    1989-01-01

    Some of the initial problems associated with the ileonal reservoir have been solved. In their place, other complications have\\u000a been recognized. Among these, the ileal pouch vaginal fistula stands out as a recently recognized difficult management problem.\\u000a This multicenter study was undertaken to gain insight into the causes for, and treatment of, pouch vaginal fistulas. Cases\\u000a were gathered from 11

  12. Outcome of “indeterminant” colitis following ileal pouch-anal anastomosis

    Microsoft Academic Search

    Michael E. Pezim; John H. Pemberton; Robert W. Beart; Bruce G. Wolff; Roger R. Dozois; Santhat Nivatvongs; Richard Devine; Duane M. Ilstrup

    1989-01-01

    To establish whether patients with indeterminant colitis (patients with ulcerative colitis whose surgical specimens also show\\u000a features of Crohn's colitis) have an adverse outcome after ileal pouch-anal anastomosis (IPAA), the authors reviewed the pathologic\\u000a reports and postoperative status of 514 consecutive patients who underwent IPAA for chronic ulcerative colitis (CUC). Twenty-five\\u000a patients (5 percent) had features of indeterminant colitis (IC),

  13. The continent ileostomy and the isolated ileal bladder.

    PubMed Central

    Madigan, M. R.

    1976-01-01

    The histories of 19 patients operated on by Kock's technique are reported. Follow-up extended from 3 years 4 months for the first case to 2 weeks for the last. There was one fatality. Some details of technique, contraindications, and complications and their treatment are discussed. Seventeen patients had a total proctocolectomy for ulcerative colitis and 2 had urinary diversion into an isolated ileal reservoir for inoperable carcinoma of the urinary bladder. PMID:944011

  14. Ileal absorption of bile acids in patients with chronic cholestasis

    Microsoft Academic Search

    Olivier Chazouillères; Philippe Marteau; Mostefa Haniche; Raymond Jian; Raoul Poupon

    1996-01-01

    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;

  15. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children

    E-print Network

    Chapman, Michael S.

    Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed

  16. Vaccination Strategies to Promote Mucosal Antibody Responses

    PubMed Central

    Chen, Kang; Cerutti, Andrea

    2011-01-01

    There are great interest and demand for the development of vaccines to prevent and treat diverse microbial infections. Mucosal vaccines elicit immune protection by stimulating the production of antibodies at mucosal surfaces and systemic districts. Being positioned in close proximity to a large community of commensal microbes, the mucosal immune system deploys a heterogeneous population of cells and a complex regulatory network to maintain the balance between surveillance and tolerance. A successful mucosal vaccine relies on leveraging the functions of these immune cells and regulatory components. This article reviews the important cellular interactions and molecular pathways underlying the induction and regulation of mucosal antibody responses and discusses their implications on mucosal vaccination. PMID:21029959

  17. Iron deficiency suppresses ileal nitric oxide synthase activity.

    PubMed

    Goldblatt, M I; Choi, S H; Swartz-Basile, D A; Nakeeb, A; Sarna, S K; Pitt, H A

    2001-01-01

    Intestinal motility disorders are more common in women of childbearing age who are prone to iron deficiency anemia. The neurotransmitters nitric oxide (NO) and acetylcholine (ACh) play a key role in ileal smooth muscle relaxation and contraction, respectively. Iron-containing heme is known to be a cofactor for nitric oxide synthase (NOS), the enzyme responsible for NO production. Therefore we tested the hypothesis that iron deficiency would downregulate ileal NOS activity without affecting the ileum's response to ACh. Twelve adult female prairie dogs were fed either an iron-supplemented (Fe+) (200 ppm) (n = 6) or an iron-deficient (Fe-) (8 ppm) (n = 6) diet for 8 weeks. Ileal circular muscle strips were harvested to measure responses to ACh and electrical field stimulation. Under nonadrenergic noncholinergic (NANC) conditions, Nomega-nitro-L-arginine (L-NNA), an NOS inhibitor, and VIP(10-28), a vasoactive intestinal peptide (VIP) inhibitor, were added prior to electrical field stimulation. NANC inhibitory responses are expressed as a percentage of optimal relaxation from EDTA. The excitatory response to ACh was similar in both groups (1.1 +/- 0.3 N/cm(2) vs. 1.5 +/- 0.3 N/cm(2), P = 0.45). The inhibitory response to electrical field stimulation under NANC conditions was greater in the Fe+ group (34.7 +/- 2.9%) compared to the Fe- group (23.9 +/- 3.2%; P<0.01). L-NNA eliminated the inhibitory response in the Fe+ group (0.02 +/- 0.02%) but not in the Fe- group (8.38 +/- 2.15%; P <0.01). VIP(10-28) led to greater relaxation in the Fe+ animals (45.8 +/- 6.6%) than in the Fe- animals (23.4 +/- 5.8%; P <0.05). Both L-NNA and VIP(10-28) had no inhibitory response (0.02 +/- 0.02%) in the Fe+ animals, whereas the Fe- animals had some residual inhibition (2.54 +/- 1.04%; P <0.05). These data suggest that ileal NANC relaxation is due to NOS and that iron deficiency results in (1) decreased NANC relaxation, (2) a compensatory relaxation due to a non-NOS, non-VIP mechanism, and (3) a normal excitatory response. We conclude that iron deficiency suppresses ileal NOS activity. PMID:11985981

  18. Chemotherapy or radiation-induced oral mucositis.

    PubMed

    Lalla, Rajesh V; Saunders, Deborah P; Peterson, Douglas E

    2014-04-01

    Oral mucositis is a significant toxicity of systemic chemotherapy and of radiation therapy to the head and neck region. The morbidity of oral mucositis can include pain, nutritional compromise, impact on quality of life, alteration in cancer therapy, risk for infection, and economic costs. Management includes general symptomatic support and targeted therapeutic interventions for the prevention or treatment of oral mucositis. Evidence-based clinical practice guidelines are available to guide clinicians in the selection of effective management strategies. PMID:24655526

  19. Voice Disorders in Mucosal Leishmaniasis

    PubMed Central

    Ruas, Ana Cristina Nunes; Lucena, Márcia Mendonça; da Costa, Ananda Dutra; Vieira, Jéssica Rafael; de Araújo-Melo, Maria Helena; Terceiro, Benivaldo Ramos Ferreira; de Sousa Torraca, Tania Salgado; de Oliveira Schubach, Armando; Valete-Rosalino, Claudia Maria

    2014-01-01

    Introduction Leishmaniasis is considered as one of the six most important infectious diseases because of its high detection coefficient and ability to produce deformities. In most cases, mucosal leishmaniasis (ML) occurs as a consequence of cutaneous leishmaniasis. If left untreated, mucosal lesions can leave sequelae, interfering in the swallowing, breathing, voice and speech processes and requiring rehabilitation. Objective To describe the anatomical characteristics and voice quality of ML patients. Materials and Methods A descriptive transversal study was conducted in a cohort of ML patients treated at the Laboratory for Leishmaniasis Surveillance of the Evandro Chagas National Institute of Infectious Diseases - Fiocruz, between 2010 and 2013. The patients were submitted to otorhinolaryngologic clinical examination by endoscopy of the upper airways and digestive tract and to speech-language assessment through directed anamnesis, auditory perception, phonation times and vocal acoustic analysis. The variables of interest were epidemiologic (sex and age) and clinic (lesion location, associated symptoms and voice quality. Results 26 patients under ML treatment and monitored by speech therapists were studied. 21 (81%) were male and five (19%) female, with ages ranging from 15 to 78 years (54.5+15.0 years). The lesions were distributed in the following structures 88.5% nasal, 38.5% oral, 34.6% pharyngeal and 19.2% laryngeal, with some patients presenting lesions in more than one anatomic site. The main complaint was nasal obstruction (73.1%), followed by dysphonia (38.5%), odynophagia (30.8%) and dysphagia (26.9%). 23 patients (84.6%) presented voice quality perturbations. Dysphonia was significantly associated to lesions in the larynx, pharynx and oral cavity. Conclusion We observed that vocal quality perturbations are frequent in patients with mucosal leishmaniasis, even without laryngeal lesions; they are probably associated to disorders of some resonance structures (larynx, pharynx and nasal and oral cavities) or even to compensation mechanisms caused by the presence of lesions in the upper airways and digestive tract. PMID:25055046

  20. Melatonin stimulates brain glutathione peroxidase activity

    Microsoft Academic Search

    L. R. Barlow-Walden; R. J. Reiter; M. Abe; M. Pablos; A. Menendez-Pelaez; L.-D. Chen; B. Poeggeler

    1995-01-01

    Exogenously administered melatonin causes a 2-fold rise in glutathione peroxidase activity within 30 min in the brain of the rat. Furthermore, brain glutathione peroxidase activity is higher at night than during the day and is correlated with high night-time tissue melatonin levels. Glutathione peroxidase is thought to be the principal enzyme eliminating peroxides in the brain. This antioxidative enzyme reduces

  1. Increased uptake of non-pathogenic E. coli via the follicle-associated epithelium in longstanding ileal Crohn's disease.

    PubMed

    Keita, A V; Salim, S Y; Jiang, T; Yang, P-C; Franzén, L; Söderkvist, P; Magnusson, K-E; Söderholm, J D

    2008-06-01

    In Crohn's disease (CD), inflammation is driven by luminal commensal micro-organisms; however, mechanisms of early phases of inflammation need further clarification. The earliest observable lesions of recurrent CD are microscopic erosions at the specialized follicle-associated epithelium (FAE), which lines the Peyer's patches. Therefore, our aim was to investigate the mucosal barrier to non-pathogenic bacteria in FAE of CD. The FAE of macroscopically normal ileum from patients with longstanding CD, ulcerative colitis, and controls was studied in Ussing chambers regarding electrophysiology and permeability to 51Cr-EDTA, horseradish peroxidase, and non-pathogenic E. coli strains. Transepithelial passage routes and uptake into dendritic cells were studied by confocal and electron microscopy. FAE of CD showed increased numbers of adherent bacteria, after E. coli exposure in Ussing chambers, as well as spontaneously in non-exposed archival surgical tissues. Further, we found increased uptake of fluorescent E. coli K-12 and HB101 across FAE of CD, but not in ulcerative colitis. Microscopy demonstrated intercellular and transcellular uptake of E. coli in CD, but only transcellular in controls. FAE exposed to E. coli demonstrated changes in conductance and 51Cr-EDTA permeability, suggesting that bacteria affected the paracellular pathway in CD mucosa. Following bacterial uptake, CD mucosa also demonstrated an increased percentage of E. coli co-localizing with dendritic cells, and augmented tissue release of TNF-alpha. Our data present novel insights into the pathophysiology of CD by demonstrating a previously unrecognized defect of FAE barrier to bacteria in ileal CD, leading to increased load of commensal bacteria to the inductive sites of mucosal immunity. PMID:18348161

  2. The effect of N -acetyl- L -cysteine on the viscosity of ileal neobladder mucus

    Microsoft Academic Search

    B. P. Schrier; W. J. Lichtendonk; J. A. Witjes

    2002-01-01

    . N-acetyl-L-cysteine (NAC) proved to be an effective mucolytic in pulmonary secretions. Our goal was to investigate the in vitro effect of NAC on viscosity of ileal neobladder mucus. The urine of a patient with an ileal neobladder was collected during the first 7 days postoperatively and stored in a refrigerator. After precipitation, the urine was decanted. The residue was

  3. Urinary diversion via a continent ileal reservoir: Clinical results in 12 patients

    Microsoft Academic Search

    N. G. Kock; A. E. Nilson; L. O. Nilsson; L. J. Norlén; B. M. Philipson

    2002-01-01

    Urinary diversion via a continent ileal reservoir has been performed in 12 patients. An isolated ileal reservoir was constructed using the technique described for patients with a continent ileostomy. The ureters were implanted into an afferent segment provided with a reflux-preventing nipple valve. There were few operative complications and no operative mortality. Late complications involving malfunction of the nipple valves

  4. Ileal impaction and jejunal enterotomy in a 4-month-old Arabian filly

    PubMed Central

    Davis, Heather A.; Munsterman, Amelia

    2012-01-01

    A 4-month-old Arabian filly was treated by surgical correction of an ileal impaction. The impaction was resolved through a distal jejunal enterotomy. One-year follow-up showed no post-operative complications secondary to the enterotomy. Jejunal enterotomy may be a surgical option for resolution of an ileal impaction. PMID:22753967

  5. Importance of mucosal healing in ulcerative colitis.

    PubMed

    Lichtenstein, Gary R; Rutgeerts, Paul

    2010-02-01

    Treatment of patients with ulcerative colitis (UC) has traditionally focused on improving symptoms, with the main objective of inducing and maintaining symptomatic remission. However, new evidence suggests that concentrating exclusively on clinical outcome measures may not be adequate to achieve long-term treatment success. Indeed, physicians should also be assessing the reduction of endoscopic activity, with the intention of achieving complete mucosal healing (defined as the absence of all mucosal ulceration, both microscopic and macroscopic, providing a sigmoidoscopy score of 0, as assessed on the Ulcerative Colitis Disease Activity Index). As a consequence of the customary reliance on symptomatic outcome measures, relatively few clinical trials have used mucosal healing or a composite including mucosal healing as a primary endpoint. This situation may soon change as new guidelines recommend the incorporation of mucosal healing into the primary endpoint of all new clinical trials in patients with UC. These recommendations are derived, in part, from data that have illustrated a correlation between mucosal healing and several important factors including long-term remission rates, disease-related complications (e.g., risk of colorectal cancer), healthcare utilization (e.g., need for colectomy), and patient quality of life. We already have drugs available to us that can effectively induce and maintain complete mucosal healing over long periods of time. This review evaluates the effect of medical therapy on mucosal healing in patients with UC and explores the importance of this outcome measure, both from the patient's perspective and clinical trial experience. Inflamm Bowel Dis 2009. PMID:19637362

  6. Vaccination Strategies for Mucosal Immune Responses

    PubMed Central

    Ogra, Pearay L.; Faden, Howard; Welliver, Robert C.

    2001-01-01

    Mucosal administration of vaccines is an important approach to the induction of appropriate immune responses to microbial and other environmental antigens in systemic sites and peripheral blood as well as in most external mucosal surfaces. The development of specific antibody- or T-cell-mediated immunologic responses and the induction of mucosally induced systemic immunologic hyporesponsiveness (oral or mucosal tolerance) depend on complex sets of immunologic events, including the nature of the antigenic stimulation of specialized lymphoid structures in the host, antigen-induced activation of different populations of regulatory T cells (Th1 versus Th2), and the expression of proinflammatory and immunoregulatory cytokines. Availability of mucosal vaccines will provide a painless approach to deliver large numbers of vaccine antigens for human immunization. Currently, an average infant will receive 20 to 25 percutaneous injections for vaccination against different childhood infections by 18 months of age. It should be possible to develop for human use effective, nonliving, recombinant, replicating, transgenic, and microbial vector- or plant-based mucosal vaccines to prevent infections. Based on the experience with many dietary antigens, it is also possible to manipulate the mucosal immune system to induce systemic tolerance against environmental, dietary, and possibly other autoantigens associated with allergic and autoimmune disorders. Mucosal immunity offers new strategies to induce protective immune responses against a variety of infectious agents. Such immunization may also provide new prophylactic or therapeutic avenues in the control of autoimmune diseases in humans. PMID:11292646

  7. 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. PMID:25630573

  8. Ileal neuroendocrine tumors and heart: not only valvular consequences.

    PubMed

    Calissendorff, Jan; Maret, Eva; Sundin, Anders; Falhammar, Henrik

    2015-04-01

    Ileal neuroendocrine tumors (NETs) often progress slowly, but because of their generally nonspecific symptoms, they have often metastasized to local lymph nodes and to the liver by the time the patient presents. Biochemically, most of these patients have increased levels of whole blood serotonin, urinary 5-hydroxyindoleacetic acid, and chromogranin A. Imaging work-up generally comprises computed tomography or magnetic resonance imaging and somatostatin receptor scintigraphy, or in recent years positron emission tomography with (68)Ga-labeled somatostatin analogs, allowing for detection of even sub-cm lesions. Carcinoid heart disease with affected leaflets, mainly to the right side of the heart, is a well-known complication and patients routinely undergo echocardiography to diagnose and monitor this. Multitasking surgery is currently recognized as first-line treatment for ileal NETs with metastases and carcinoid heart disease. Open heart surgery and valve replacement are advocated in patients with valvular disease and progressive heart failure. When valvulopathy in the tricuspid valve results in right-sided heart failure, a sequential approach, performing valve replacement first before intra-abdominal tumor-reductive procedures are conducted, reduces the risk of bleeding. Metastases to the myocardium from ileal NETs are seen in <1-4.3 % of patients, depending partly on the imaging technique used, and are generally discovered in those affected with widespread disease. Systemic treatment with somatostatin analogs, and sometimes alpha interferon, is first-line medical therapy in metastatic disease to relieve hormonal symptoms and stabilize the tumor. This treatment is also indicated when heart metastases are detected, with the addition of diuretics and fluid restriction in cases of heart failure. Myocardial metastases are rarely treated by surgical resection. PMID:25319177

  9. [A case of curatively resected, locally advanced ascending colon cancer with ileal conduit invasion].

    PubMed

    Kameyama, Hitoshi; Shimada, Yoshifumi; Nogami, Hitoshi; Nakano, Mae; Nakano, Masato; Sakata, Jun; Kobayashi, Takashi; Minagawa, Masahiro; Kosugi, Shinichi; Koyama, Yu; Wakai, Toshifumi

    2014-11-01

    A 71 -year-old man was referred to our hospital because of repeated bowel obstruction. He had previously undergone cystectomy with ileal conduit urinary diversion for the treatment of bladder cancer at the age of 28 years. Computed tomography revealed a mass in the ascending colon. Ileostomy was initially performed because of poor general condition that improved with postoperative nutrition management. Enema findings revealed ascending colon cancer and we therefore decided to perform curative surgery. Intraoperative findings revealed that the ascending colon cancer had invaded the ileal conduit. However, it was confirmed that the ureter-ileal conduit anastomosis and the mesentery of the ileal conduit could be preserved. We performed right colectomy and partial resection of the ileal conduit with curative intent. The pathological stage was pT4bpN0cM0, pStage II. There were no signs of recurrence 15 months after curative surgery. PMID:25731293

  10. 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

  11. Pulmonary and Ileal Tuberculosis Presenting as Fever of Undetermined Origin

    PubMed Central

    Surewad, Gajanan; Lobo, Ivona

    2014-01-01

    A 12-year-old girl presented with prolonged fever with no obvious focus on either history or clinical examination. High-resolution computerized tomography of the chest revealed the ‘tree-in-bud’ sign in the right lung and necrotic mediastinal lymph nodes. Barium meal showed multiple ileal strictures. The child was treated with anti-tuberculous therapy for six months. At follow-up six months later, the child had gained weight and had no signs of intestinal obstruction. Tuberculosis is a common cause of fever of undetermined origin and should be investigated for especially in countries with a high prevalence. PMID:25478420

  12. Synchronous ileal carcinoid and primary colonic neoplasms: a case report.

    PubMed

    Aslam, Muhammad Imran; Salha, Imen Ben; Muller, Salli; Jameson, John Stuart

    2009-01-01

    Primary colonic tumours with synchronous ileal carcinoid tumours are rare in occurrence and are mainly found incidentally on autopsies or pathological examination of resected surgical specimens. This article describes a case of adenomatous colonic polyps, adenocarcinoma of sigmoid colon and concurrent malignant carcinoid tumour of ileocaecal junction, detected on colonoscopic examination. The radiological staging investigations revealed no distant spread of disease. The patient was effectively treated with subtotal colectomy, resection of terminal ileum, excision of locoregional lymph nodes and the bowel continuity was restored with stapled ileo-rectal anastomosis. This article is as an example of concomitant presence of two types of malignant tumours, effectively managed surgically. PMID:19918418

  13. Stapled mucosectomy: an alternative technique for the removal of retained rectal mucosa after ileal pouch-anal anastomosis.

    PubMed

    Ertem, Metin; Ozben, Volkan

    2011-12-01

    Restorative proctocolectomy (RPC), when performed with a stapled ileal pouch-anal anastomosis (IPAA), allows the retention of the rectal mucosa above the dentate line and can result in disease persistence or recurrence, as well as neoplastic lesions in patients with ulcerative colitis (UC). We report the case of a patient with chronic UC who underwent staple mucosectomy, which is an alternative technique that evolved from stapled hemorrhoidopexy, rather than more traditional procedures. The patient had undergone laparoscopic RPC with a stapled IPAA 2 cm above the dentate line and a temporary loop ileostomy. Because the histopathology showed low-grade dysplasia in the proximal rectum, stapled mucosectomy with a 33-mm circular stapler kit at the time of ileostomy closure was scheduled. Following the application of a purse-string suture 1 cm above the dentate line, the stapler was inserted with its anvil beyond the purse-string and was fired. The excised rectal tissue was checked to ensure that it was a complete cylindrical doughnut. Histopathology of the excised tissue showed chronic inflammation. There were no complications during a follow-up period of 5 months. Because it preserves the normal rectal mucosal architecture and avoids a complex mucosectomy surgery, stapled mucosectomy seems to be a technically feasible and clinically acceptable alternative to the removal of rectal mucosa retained after RPC. PMID:22195257

  14. Increased leukotriene B4 release from ileal pouch mucosa in ulcerative colitis compared with familial adenomatous polyposis.

    PubMed Central

    Gertner, D J; Rampton, D S; Madden, M V; Talbot, I C; Nicholls, R J; Lennard-Jones, J E

    1994-01-01

    Pouchitis may complicate the construction of an ileal pouch after colectomy for ulcerative colitis (UC) but not familial adenomatous polyposis (FAP). To examine whether differences in eicosanoid metabolism might explain why pouchitis is largely confined to UC patients, this study compared arachidonic acid stimulated release of immunoreactive leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) from macroscopically uninflamed pouch mucosal biopsy specimens incubated in vitro from patients with UC and FAP. The study also compared eicosanoid release from inflamed and uninflamed pouches in patients with UC. In uninflamed pouches, median LTB4 release was nearly twice as high in UC as in FAP (p = 0.001), but there was no significant difference in PGE2 production. In UC, stimulated eicosanoid release from uninflamed functioning pouch mucosa was not significantly different from that from either ileostomy or defunctioned pouch mucosa. LTB4 and PGE2 release were significantly greater from inflamed than uninflamed pouch mucosa in UC (p = 0.001 and 0.01, respectively). Leukotriene synthesis inhibition or receptor antagonism, or both merit therapeutic evaluation in pouchitis. Increased release of LTB4 from endoscopically normal pouch mucosa suggests increased 5-lipoxygenase activity in patients with UC and could contribute to their predisposition to pouchitis. PMID:7959200

  15. IL-1? Mediated Chorioamnionitis Induces Depletion of FoxP3+ Cells and Ileal Inflammation in the Ovine Fetal Gut

    PubMed Central

    Wolfs, Tim G. A. M.; Kallapur, Suhas G.; Polglase, Graeme R.; Pillow, J. Jane; Nitsos, Ilias; Newnham, John P.; Chougnet, Claire A.; Kroon, Elke; Spierings, Julia; Willems, Coen H. M. P.; Jobe, Alan H.; Kramer, Boris W.

    2011-01-01

    Background Endotoxin induced chorioamnionitis increases IL-1 and provokes an inflammatory response in the fetal ileum that interferes with intestinal maturation. In the present study, we tested in an ovine chorioamnionitis model whether IL-1 is a major cytokine driving the inflammatory response in the fetal ileum. Method Sheep bearing singleton fetuses received a single intraamniotic injection of recombinant ovine IL-1? at 7, 3 or 1 d before caesarian delivery at 125 days gestational age (term?=?150 days). Results 3 and 7 d after IL-1? administration, intestinal mRNA levels for IL-4, IL-10, IFN-? and TNF-? were strongly elevated. Numbers of CD3+ and CD4+ T-lymphocytes and myeloidperoxidase+ cells were increased whereas FoxP3+ T-cells were detected at low frequency. This increased proinflammatory state was associated with ileal mucosal barrier loss as demonstrated by decreased levels of the intestinal fatty acid binding protein and disruption of the tight junctional protein ZO-1. Conclusion Intraamniotic IL-1? causes an acute detrimental inflammatory response in the ileum, suggesting that induction of IL-1 is a critical element in the pathophysiological effects of endotoxin induced chorioamnionitis. A disturbed balance between T-effector and FoxP3+ cells may contribute to this process. PMID:21479249

  16. Intestinal mucosal atrophy and adaptation

    PubMed Central

    Shaw, Darcy; Gohil, Kartik; Basson, Marc D

    2012-01-01

    Mucosal adaptation is an essential process in gut homeostasis. The intestinal mucosa adapts to a range of pathological conditions including starvation, short-gut syndrome, obesity, and bariatric surgery. Broadly, these adaptive functions can be grouped into proliferation and differentiation. These are influenced by diverse interactions with hormonal, immune, dietary, nervous, and mechanical stimuli. It seems likely that clinical outcomes can be improved by manipulating the physiology of adaptation. This review will summarize current understanding of the basic science surrounding adaptation, delineate the wide range of potential targets for therapeutic intervention, and discuss how these might be incorporated into an overall treatment plan. Deeper insight into the physiologic basis of adaptation will identify further targets for intervention to improve clinical outcomes. PMID:23197881

  17. Regulation of airway mucosal hydration.

    PubMed

    Paisley, Derek; Gosling, Martin; Danahay, Henry

    2010-05-01

    Ion channels control the hydration status of the airway epithelium through apical anion secretion and cation absorption, which is accompanied by osmotically obligated water. The key channels in this process are the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), which is principally responsible for Cl(-) secretion by airway epithelial cells, and the epithelial Na(+) channel (ENaC), which is responsible for the absorption of Na ions. In CF, defective CFTR-mediated Cl(-) secretion and an accompanying upregulation in ENaC-mediated Na absorption results in a reduction in airway surface liquid volume, leading to poorly hydrated mucus and impaired mucociliary clearance. Restoration of normal airway hydration by modulation of ion channel activity represents an important therapeutic strategy for CF. CFTR corrector and potentiator compounds are being developed with the aim of recovering normal Cl(-) secretion. Ca(2+)-activated Cl(-) channels (CaCCs) are expressed by the respiratory epithelia and are reported to be functionally upregulated in CF and offer a 'surrogate' pathway for Cl(-) secretion. TMEM16A has recently been described as a CaCC in the airway epithelium and, as such, represents an alternative target for restoring Cl(-) secretion in CF. An alternative therapeutic strategy for CF is to inhibit ENaC, thereby blocking excessive Na absorption. This can be achieved by direct blockade of ENaC or inhibition of the channel-activating proteases (CAPs), whose activity regulates ENaC function. This review will describe the regulation of airway mucosal hydration by ion channels and the efforts currently underway to restore normal mucosal hydration in disease patients by modulating the function of these channels. PMID:22111616

  18. Role of sulfhydryls in mucosal injury caused by ethanol: relation to microvascular permeability, gastric motility and cytoprotection

    SciTech Connect

    Takeuchi, K.; Okada, M.; Niida, H.; Okabe, S.

    1989-02-01

    The relationship between gastric mucosal glutathione (GSH) levels, vascular permeability, gastric motility and mucosal injury caused by ethanol was investigated in rats. Oral administration of 50% ethanol (1 ml) produced elongated reddish bands of lesions in the mucosa with a significant reduction of GSH levels and increase of microvascular permeability. These lesions were significantly inhibited by pretreatment with s.c. administered diethylmaleate (DEM: 1 ml/kg), cysteamine (100 mg/kg) and 16, 16-dimethyl prostaglandin E2 (dmPGE2, 10 micrograms/kg) but worsened markedly by N-ethylmaleimide (NEM: 10 mg/kg). Irrespective of whether the animals were treated with 50% ethanol or not, the mucosal GSH levels were significantly decreased or increased, respectively, by DEM or cysteamine, and were not affected by both NEM and dmPGE2. NEM significantly enhanced the vascular permeability in the absence or presence of ethanol (greater than 10%), whereas other agents significantly inhibited only the increased vascular permeability caused by ethanol. On the other hand, gastric motility was potently and persistently inhibited by either DEM, cysteamine or dmPGE2 at the doses which prevented ethanol-induced mucosal injury, whereas NEM had no effect on the motility. These results suggest that 1) the mucosal GSH levels do not relate directly to either development or prevention of ethanol-induced gastric injury, 2) potentiation by NEM of the mucosal injury may be accounted for by its enhancement of the vascular permeability and 3) inhibition of gastric motility may be associated with prevention of mucosal lesions.

  19. Transmural ileal ganglioneuromatosis in a young Boer goat (Capra hircus).

    PubMed

    Sheley, M F; Higgins, R J; Mete, A

    2014-01-01

    A diagnosis of transmural ileal ganglioneuromatosis was made in a 15-day-old goat that was found dead following a period of diarrhoea and inappetence. Grossly, the entire length of the wall of the ileum was pale and firm with a variably segmental to transmural thickening. Microscopically, the ileal transmural thickening was due to a diffuse proliferation of both ganglionic and glial cells forming cell nests or packets that infiltrated the wall and into the mesentery surrounding a mesenteric lymph node. The neoplastic ganglionic cells were immunoreactive for S100, synaptophysin and triple neurofilament, while the glial spindle cells were immunoreactive with glial fibrillary acidic protein, S100 and laminin confirming their Schwann cell identity. Nerve fibres expressing neurofilament protein 200 and phosphorylated neurofilament (SMI-31) were observed rarely. Ganglioneuromatosis is defined as diffuse exuberant proliferation of all components of the intestinal ganglionic plexuses. In man, the transmural form has more grave clinical consequences than a focal pattern and is commonly associated with germline mutations in the RET proto-oncogene. Whether there is any comparable molecular genetic abnormality in animals remains unknown; however, ganglioneuromatosis needs to be included in the differential diagnosis of tumours of the autonomic enteric nervous system. PMID:24975898

  20. Non-Traumatic Ileal Perforation: A Retrospective Study

    PubMed Central

    Singh, Gurjit; Dogra, Bharat Bhushan; Jindal, Neha; Rejintal, Santhosh

    2014-01-01

    Objective: To determine clinical features, operative findings and post-operative complications in patients operated for non-traumatic ileal perforation and to discuss the role of typhoid vaccination. Materials and Methods: A retrospective study was carried out from 2009-2010. Seven patients were admitted through casualty as cases of acute abdomen. Underlying conditions were typhoid ulcers (4 patients) and non-specific etiology (3 patients). Diagnosis was made on clinical grounds, laboratory investigations, radiology and operative findings. Exploratory laporotomy was done. Different variables studied post-operatively were wound infection, residual abscess, recurrence and delayed post-operative complications. Results: Tenderness, distension and rigidity were found in maximum patients. Gases under diaphragm and air fluid levels were common radiological findings. However, widal test and blood culture for S. typhi was positive in four patients. Six patients had single perforation and one patient had two perforations, all being on antimesentric border of ileum. Maximum patients had peritoneal collection of less than 1000 ml. In five patients simple closure of perforation was done and in remaining two resection with end to side ileotransverse anatomosis was required. Wound infection and residual intraabdominal abscess were found in one patient each. Conclusion: Management criteria remain same in typhoid and non-specific perforations. Commonest cause of ileal perforation is typhoid fever in our country, so immunization against typhoid beyond 18 years of age is recommended. PMID:25161970

  1. Terminal ileal intubation and biopsy in routine colonoscopy practice.

    PubMed

    Neilson, Laura J; Bevan, Roisin; Panter, Simon; Thomas-Gibson, Siwan; Rees, Colin J

    2015-05-01

    This special report focuses on the current literature regarding the utility of terminal ileal (TI) intubation and biopsy. The authors reviewed the literature regarding the clinical benefit of TI intubation at the time of colonoscopy and also the evidence for TI intubation as a colonoscopy quality indicator. TI intubation is useful to identify ileal diseases such as Crohn's disease and additionally as a means of confirming colonoscopy completion when classical caecal landmarks are not confidently seen. Previous studies have demonstrated that TI intubation has variable yield but may be more useful in patients presenting with diarrhea. Reported rates of TI intubation at colonoscopy vary. The authors demonstrate that terminal ileoscopy is feasible in clinical practice and sometimes yields additional clinical information. Additionally it may be used as an indicator of colonoscopy completion. It may be particularly helpful when investigating patients with diarrhea, abnormalities seen on other imaging modalities and patients with suspected Crohn's disease. TIs reported as normal at endoscopy have a low yield when biopsied; however, biopsies from abnormal-looking TIs demonstrate a higher yield and have greater diagnostic value. PMID:25582839

  2. Reduced Paneth cell -defensins in ileal Crohn's disease

    Microsoft Academic Search

    Jan Wehkamp; Nita H. Salzman; Edith Porter; Sabine Nuding; Michael Weichenthal; Robert E. Petras; Bo Shen; Elke Schaeffeler; Matthias Schwab; Rose Linzmeier; Ryan W. Feathers; Hiutung Chu; Heriberto Lima Jr.; Klaus Fellermann; Tomas Ganz; Eduard F. Stange; Charles L. Bevins

    2005-01-01

    The pathogenesis of Crohn's disease (CD), an idiopathic inflammatory bowel disease, is attributed, in part, to intestinal bacteria that may initiate and perpetuate mucosal inflammation in genetically susceptible individuals. Paneth cells (PC) are the major source of antimicrobial peptides in the small intestine, including human -defensins HD5 and HD6. We tested the hypothesis that reduced expression of PC -defensins compromises

  3. Mucosal healing in inflammatory bowel disease.

    PubMed

    Osterman, Mark T

    2013-03-01

    It is becoming increasingly recognized that purely clinical endpoints may not be sufficient in the treatment of patients with inflammatory bowel disease. As such, mucosal disease assessment has become a prominent component of the majority of recent clinical trials in Crohn's disease and ulcerative colitis. There is mounting evidence that the attainment of mucosal healing leads to improved clinical outcomes in both Crohn's disease and ulcerative colitis. However, the use of mucosal healing as a therapeutic endpoint in inflammatory bowel disease is in its early stages, as a number of issues limit its application to routine clinical practice. PMID:23340060

  4. Emerging regulatory paradigms in glutathione metabolism.

    PubMed

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

    2014-01-01

    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

  5. Construction of a continent outlet using an ileal valve, an in vivo animal model.

    PubMed

    Türkölmez, Kadir; Gö?ü?, Ca?atay; Baltaci, Sümer

    2003-07-01

    The efficacy of a new continent outlet mechanism using a simple ileal valve in a continent cutaneous urinary diversion was evaluated. In eight mongrel dogs, a 50 cm distal ileal segment was isolated. The distal 41 cm of the isolated segment was opened along the antimesenteric border while the proximal 9 cm was not detubularized. The distal 6 cm part of the non-detubularized segment was tapered over a 30 F catheter and closed with continuous 3/0 polyglactin sutures. In order to create a valve, this 6 cm tapered ileal segment was wrapped anteriorly by the most distal part of the detubularized ileal segment. The remaining part of the detubularized ileal segment was folded into a U configuration. The posterior plate was completed by joining the limbs of the U with running absorbable sutures. Afterwards, the reservoir was closed by folding the ileal plate in half in the opposite direction to which it was opened. The intact proximal 3 cm part of the isolated ileal segment was brought out to the abdominal skin. A pouchogram of the reservoir and video-urodynamic studies were performed to evaluate the efficacy of the continent outlet 18-20 weeks after surgery. Video-urodynamic studies and pouchograms of the reservoirs revealed no leakage from the continent outlet in any dog. Reservoirs had a mean capacity of 413 +/- 51 ml (range 356-447 ml). When the reservoir was filled to maximum capacity, the average total reservoir pressure was 29 +/- 4.7 cm H2O (range 21-45). This procedure, using a single ileal segment for construction of the continent cutaneous urinary diversion, is simple and safe. The ileal valve mechanism serves as a reliable continent outlet system. PMID:12709771

  6. 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.

  7. Cancer treatment-induced oral mucositis.

    PubMed

    Alterio, Daniela; Jereczek-Fossa, Barbara Alicja; Fiore, Maria Rosaria; Piperno, Gaia; Ansarin, Mohssen; Orecchia, Roberto

    2007-01-01

    Oral mucositis is one of the main complications in non-surgical cancer treatments. It represents the major dose-limiting toxicity for some chemotherapeutic agents, for radiotherapy of the head and neck region and for some radiochemotherapy combined treatments. Many reviews and clinical studies have been published in order to define the best clinical protocol for prophylaxis or treatment of mucositis, but a consensus has not yet been obtained. This paper represents an updated review of prophylaxis and treatment of antineoplastic-therapy-related mucositis using a MEDLINE search up to May 2006, in which more than 260 clinical studies have been found. They have been divided according to antineoplastic therapy (chemotherapy, radiotherapy, chemo-radiotherapy, high-dose chemotherapy). The prophylactic or therapeutic use of the analysed agents, the number of enrolled patients and the study design (randomized or not) were also specified for most studies. Accurate pre-treatment assessment of oral cavity hygiene, frequent review of symptoms during treatment, use of traditional mouthwashes to obtain mechanical cleaning of the oral cavity and administration of some agents like benzydamine, imidazole antibiotics, tryazolic antimycotics, povidone iodine, keratinocyte growth factor and vitamin E seem to reduce the intensity of mucositis. Physical approaches like cryotherapy, low energy Helium-Neon laser or the use of modern radiotherapy techniques with the exclusion of the oral cavity from radiation fields have been shown to be efficacious in preventing mucositis onset. Nevertheless a consensus protocol of prophylaxis and treatment of oral mucositis has not yet been obtained. PMID:17465250

  8. NK Cells in Mucosal Defense against Infection

    PubMed Central

    Ivanova, Daria; Krempels, Ryan; Ryfe, Jennyfer; Weitzman, Kaitlyn; Stephenson, David; Gigley, Jason P.

    2014-01-01

    Conventional natural killer cells (NK cells) provide continual surveillance for cancer and rapid responses to infection. They develop in the bone marrow, emerge as either NK precursor cells, immature, or mature cells, and disperse throughout the body. In the periphery NK cells provide critical defense against pathogens and cancer and are noted to develop features of adaptive immune responses. In the tightly regulated and dynamic mucosal tissues, they set up residency via unknown mechanisms and from sources that are yet to be defined. Once resident, they appear to have the ability to functionally mature dependent on the mucosal tissue microenvironment. Mucosal NK cells play a pivotal role in early protection through their cytolytic function and IFN? production against bacteria, fungi, viruses, and parasitic infections. This review presents what is known about NK cell development and phenotypes of mucosal tissue resident conventional NK cells. The question of how they come to reside in their tissues and published data on their function against pathogens during mucosal infection are discussed. Dissecting major questions highlighted in this review will be important to the further understanding of NK cell homing and functional diversity and improve rational design of NK cell based therapies against mucosal infection. PMID:25197644

  9. Neonatal Bartter syndrome associated with ileal atresia and cystic fibrosis.

    PubMed

    Akuma, A O; Mittal, S K; Sambo, A A

    2013-01-01

    A rare case of neonatal Bartter syndrome presenting with severe hyperkalemia is reported in a preterm child born to consanguineous parents. This child also had ileal atresia, and meconium plugs were found at laparotomy. The diagnosis of cystic fibrosis was subsequently made on genetic testing. Despite full intensive care management and surgical interventions, he died of respiratory failure after 70 days. This is the first reported case of such conglomeration of pathologies in a newborn child. Second, in highlighting this case we want clinicians to be aware that a subtype of neonatal Bartter syndrome can present with initial hyperkalemia so that an erroneous diagnosis of pseudohypoaldosteronism is not made when this is seen in combination with hyponatraemia and hyperrenin hyperaldosteronism [corrected]. PMID:23580805

  10. Heterotopic Pancreas: A Rare Cause of Ileo-Ileal Intussusception

    PubMed Central

    Monier, Ahmed; Awad, Ahmed; Szmigielski, Wojciech; Muneer, Mohamed; Alrashid, Amal; Darweesh, Adham; Hassan, Heba

    2014-01-01

    Background Heterotopic pancreas is a rare developmental anomaly defined as pancreatic tissue found on ectopic sites without contiguity with the main pancreas. An isolated heterotopic pancreas as a cause of bowel intussusception is extremely rare. Case Report A case of 47-year old male with multiple episodes of melena, constipation and abdominal pain for one year duration is presented. CT eneterography revealed a large circumferential lesion involving the terminal ileum that acted as a leading point to an ileo-ileal intussusception. The resection of the lesion and related bowel segment was carried out. The histopathological examination confirmed the excised lesion as a heterotopic pancreatic tissue. Conclusions Though a rare entity, heterotopic pancreas should be considered in the differential diagnosis of bowel intussusception. PMID:25302087

  11. Ileal ganglioneuromatosis in a piglet: histopathological and immunohistochemical studies.

    PubMed

    Quiroga, M A; Lozada, M I; Madariaga, G; Cappucio, J A; Machuca, M A; Barrales, H; Perez, E M; Perfumo, C J

    2014-11-01

    Ganglioneuromatosis (GNM) is a rare condition characterized by the benign proliferation of ganglion cells, nerve fibres and supporting cells of the enteric nervous system. Necropsy examination of a female piglet weighing 4 kg revealed a well-demarcated 20 cm segment of terminal ileum with thickening of the wall. Microscopically, the lamina propria was infiltrated by enteric glial cells and large ganglion cells. Within the submucosal and muscular layers, aggregates of neurons were interlaced by Schwann cells and enteric glial cells arranged in concentric rings. Immunohistochemically, the neurons were weakly labelled for S-100 and neuron-specific enolase, Schwann cells expressed S-100 and vimentin and enteric glial cells expressed glial fibrillary acidic protein and S-100. Pathological and immunohistochemical findings supported the diagnosis of ileal GNM. PMID:25443431

  12. Gastrointestinal hemorrhage due to ileal metastasis from primary lung cancer

    PubMed Central

    Liu, Wei; Zhou, Wei; Qi, Wei-Lin; Ma, Ya-Dan; Xu, Yun-Yun

    2015-01-01

    We report a patient with small intestinal metastasis from lung squamous cell carcinoma. A 66-year-old man who underwent radical lung cancer surgery was admitted to our hospital. Before starting his fifth cycle of chemotherapy, he was found to have a positive fecal occult blood test. Abdominal computed tomography scan revealed an ileal tumor with mesenteric lymph node enlargement. He underwent laparoscopic resection of the involved small intestine and mesentery. Histopathological analysis confirmed metastasis from lung cancer. We conducted a review of the literature and 64 documented cases of small intestinal metastasis from lung cancer were found. The pathologic diagnosis, clinical presentation, site of metastasis, and survival time in these cases were reviewed. PMID:25805957

  13. Gastrointestinal hemorrhage due to ileal metastasis from primary lung cancer.

    PubMed

    Liu, Wei; Zhou, Wei; Qi, Wei-Lin; Ma, Ya-Dan; Xu, Yun-Yun

    2015-03-21

    We report a patient with small intestinal metastasis from lung squamous cell carcinoma. A 66-year-old man who underwent radical lung cancer surgery was admitted to our hospital. Before starting his fifth cycle of chemotherapy, he was found to have a positive fecal occult blood test. Abdominal computed tomography scan revealed an ileal tumor with mesenteric lymph node enlargement. He underwent laparoscopic resection of the involved small intestine and mesentery. Histopathological analysis confirmed metastasis from lung cancer. We conducted a review of the literature and 64 documented cases of small intestinal metastasis from lung cancer were found. The pathologic diagnosis, clinical presentation, site of metastasis, and survival time in these cases were reviewed. PMID:25805957

  14. Neonatal Bartter syndrome associated with ileal atresia and cystic fibrosis

    PubMed Central

    Akuma, A. O.; Mittal, S. K.; Sambo, A. A.

    2013-01-01

    A rare case of neonatal Bartter syndrome presenting with severe hyperkalemia is reported in a preterm child born to consanguineous parents. This child also had ileal atresia, and meconium plugs were found at laparotomy. The diagnosis of cystic fibrosis was subsequently made on genetic testing. Despite full intensive care management and surgical interventions, he died of respiratory failure after 70 days. This is the first reported case of such conglomeration of pathologies in a newborn child. Second, in highlighting this case we want clinicians to be aware that a subtype of neonatal Bartter syndrome can present with initial hyperkalemia so that an erroneous diagnosis of pseudohypoaldosteronism is not made when this is seen in combination with hyperkalemia and hyperrenin hyperaldosteronism. PMID:23580805

  15. Effect of diallyl disulfide on acute gastric mucosal damage induced by alcohol in rats.

    PubMed

    Lee, I-C; Baek, H-S; Kim, S-H; Moon, C; Park, S-H; Kim, S-H; Shin, I-S; Park, S-C; Kim, J-C

    2015-03-01

    This study investigated the gastroprotective effects of diallyl disulfide (DADS), a secondary organosulfur compound derived from garlic (Allium sativum L.) on experimental model of ethanol (EtOH)-induced gastric ulcer in rats. The antiulcerogenic activity of DADS was evaluated by gross/histopathological inspection, pro-inflammatory cytokines, and lipid peroxidation with antioxidant enzyme activities in the stomach. DADS (100 mg/kg) was administered by oral gavage 2 h prior to EtOH treatment (5 ml/kg). The animals were killed 1 h after receiving EtOH treatment. Pretreatment with DADS attenuated EtOH-induced gastric mucosal injury, as evidenced by decreased severity of hemorrhagic lesions and gastric ulcer index upon visual inspection. DADS also prevented histopathological alterations and gastric apoptotic changes caused by EtOH. An increase in tumor necrosis factor-? (TNF-?) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-? and interleukin 6 levels. In contrast, DADS effectively suppressed production of pro-inflammatory mediators induced by EtOH. Furthermore, DADS prevented the formation of gastric malondialdehyde and the depletion of reduced glutathione content and restored antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase in the gastric tissues of EtOH-treated rats. These results indicate that DADS prevents gastric mucosal damage induced by acute EtOH administration in rats and that the protective effects of DADS may be due to its potent antioxidant and anti-inflammatory activities. PMID:24972622

  16. Relationship between Ileal symbiont intracellularis and porcine proliferative enteritis.

    PubMed Central

    Jones, G F; Ward, G E; Murtaugh, M P; Rose, R; Gebhart, C J

    1993-01-01

    The relationship between Ileal symbiont (IS) intracellularis, formerly known as a Campylobacter-like organism, and porcine proliferative enteritis (PE) was studied by use of pigs with experimentally transmitted PE. Twenty one pigs were experimentally inoculated with homogenized ileal mucosa from a pig that died with PE, and 7 were maintained as uninoculated controls. Fecal samples were collected, and pigs were necropsied weekly postinoculation. Light microscopy and electron microscopy were used to examine tissues for lesions of PE and infectious agents. DNA was extracted from the fecal samples and assayed for the presence of sequences specific for IS intracellularis by dot blot hybridization and polymerase chain reaction amplification. IS intracellularis was detected by the polymerase chain reaction in the feces of 20 of 21 inoculated pigs but not in the feces of uninoculated pigs. Seven inoculated pigs but no uninoculated pigs were detected shedding IS intracellularis by dot blot hybridization. Shedding was detected 1 to 5 weeks after inoculation, and clinical signs were seen in the second to fifth weeks after inoculation. Few pigs without lesions of PE were found to shed IS intracellularis. There was a highly significant association between the presence of IS intracellularis in feces or tissue and the presence of microscopic proliferative lesions and between the severity of the lesions of PE and the percentage of IS intracellularis-infected intestinal crypts. Pigs that ceased shedding IS intracellularis were significantly less likely to have proliferative lesions. These and previous reports are consistent with the hypothesis that IS intracellularis is a necessary causative agent of PE. Images PMID:8225599

  17. Effects of Chronic Dietary Cadmium on Hepatic Glutathione Levels and Glutathione Peroxidase Activity in Starlings (Sturnus vulgaris)

    E-print Network

    Pilastro, Andrea

    Effects of Chronic Dietary Cadmium on Hepatic Glutathione Levels and Glutathione Peroxidase cadmium on the levels of hepatic glutathione (GSH) and on the activity of the glutathione peroxidase is the enzyme system of glutathione peroxidases (GSH-Px), both selenium-dependent (Se GSH-Px, EC 1

  18. Expression of glutathione, glutathione peroxidase and glutathione S-transferase pi in canine mammary tumors

    PubMed Central

    2014-01-01

    Background Glutathione (GSH) is one of the most important agents of the antioxidant defense system of the cell because, in conjunction with the enzymes glutathione peroxidase (GSH-Px) and glutathione S transferase pi (GSTpi), it plays a central role in the detoxification and biotransformation of chemotherapeutic drugs. This study evaluated the expression of GSH and the GSH-Px and GSTpi enzymes by immunohistochemistry in 30 canine mammary tumors, relating the clinicopathological parameters, clinical outcome and survival of the bitches. In an in vitro study, the expression of the genes glutamate cysteine ligase (GCLC) and glutathione synthetase (GSS) that synthesize GSH and GSH-Px gene were verified by qPCR and subjected to treatment with doxorubicin, to check the resistance of cancer cells to chemotherapy. Results The immunohistochemical expression of GSH, GSH-Px and GSTpi was compared with the clinical and pathological characteristics and the clinical outcome in the bitches, including metastasis and death. The results showed that high immunoexpression of GSH was correlated to the absence of tumor ulceration and was present in dogs without metastasis (P??0.05). The analysis of the relative expression of genes responsible for the synthesis of GSH (GCLC and GSS) and GSH-Px by quantitative PCR was done with cultured cells of 10 tumor fragments from dogs with mammary tumors. The culture cells showed a decrease in GCLC and GSS expression when compared with no treated cells (P?

  19. Glutathione and its role in cellular functions

    Microsoft Academic Search

    Helmut Sies

    1999-01-01

    Glutathione (GSH) is the major cellular thiol participating in cellular redox reactions and thioether formation. This article serves as introduction to the FRBM Forum on glutathione and emphasizes cellular functions: What is GSH? Where does it come from? Where does it go? What does it do? What is new and noteworthy? Research tools, historical remarks, and links to current trends.

  20. Effect of glutathione on horseradish peroxidase activity

    NASA Astrophysics Data System (ADS)

    Ochoe de Aspuru, Eduardo; Lourdes Zatón, Ana M. a.

    1999-09-01

    The inhibition by glutathione of guaiacol peroxidation by horseradish peroxidase (HRP) was investigated. The concentration of tetraguaiacol synthesized was determined by the absorbancy changes at 470 nm. Glutathione inhibits HRP activity in a noncompetitive way, with Km, Kcat and Ki values of 5.9×10 -3 M, 2.5×10 6 min -1 and 3×10 -8 M, respectively.

  1. Glutathione Resins I. List of Components

    E-print Network

    Lebendiker, Mario

    that is applicable for up to 50 g of E. coli cells. Other extraction methods can be used with varying recovery purifications of up to 10 mg of GST-tagged protein per column. · Five Glutathione-Uniflow Columns Each column Clontech · www.clontech.com · 800-662-2566 #12;GlutathioneResinProtocol · Polypropylene tubes · Centrifuge

  2. Role of glutathione in intracellular copper transport

    E-print Network

    Ha, Chenxiang

    1994-01-01

    of glutathione is sufficient to chelate Cu at 50 rtm as long as 180 min before the complex releases Cu to other ligands or organelles in the cell. Evidence obtained from this study suggests that Zn does not form a stable complex with glutathione. Antagonistic...

  3. Linked thioredoxin-glutathione systems in platyhelminths

    Microsoft Academic Search

    Gustavo Salinas; Murray E. Selkirk; Cora Chalar; Rick M. Maizels; Cecilia Fernández

    2004-01-01

    The thioredoxin and glutathione systems play a central role in thiol-disulfide redox homeostasis in many organisms by providing electrons to essential enzymes, and defence against oxidative stress. These systems have recently been characterized in platyhelminth parasites, and the emerging biochemical scenario is the existence of linked processes with the enzyme thioredoxin glutathione reductase supplying reducing equivalents to both pathways. In

  4. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...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 cells). Glutathione measurements are used in the...

  5. Characterization of adenosine receptors on rat ileum, ileal longitudinal muscle and muscularis mucosae

    Microsoft Academic Search

    Julia Nicholls; Susanna M. O Hourani

    1997-01-01

    Adenosine receptors were studied in isolated rat ileum, ileal longitudinal muscle and muscularis mucosae, using a range of agonists and an antagonist. In the rat ileal longitudinal muscle adenosine receptor agonists relaxed the tissues. N6-cyclopentyladenosine (CPA) was more potent than 5?-N-ethylcarboxamidoadenosine (NECA) or adenosine and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (1 nM) gave a 5-fold parallel shift to the right of the concentration–response

  6. Direct measurement of first-pass ileal clearance of a bile acid in humans

    Microsoft Academic Search

    G. Galatola; R. P. Jazrawi; C. Bridges; A. E. Joseph; T. C. Northfield

    1991-01-01

    The purpose of this study was to develop and validate a method of directly measuring ileal bile acid absorption efficiency during a single enterohepatic cycle (first-pass ileal clearance). This has become feasible for the first time because of the availability of the synthetic gamma-labeled bile acid 75Selena-homocholic acid-taurine (75SeHCAT). Together with the corresponding natural bile acid cholic acid-taurine (labeled with

  7. The duodenal mucosal bicarbonate secretion.

    PubMed

    Sjöblom, Markus

    2005-01-01

    The duodenal lumen is exposed to aggressive factors with a high potential to cause damage to the mucosa. Bicarbonate secretion by the duodenal mucosa is accepted as the primary important defense mechanism against the hydrochloric acid intermittently expelled from the stomach. The present work concerns both the influence of the central nervous system and the effects of the hormone melatonin on duodenal bicarbonate secretion in anesthetized rats in vivo as well as effects of melatonin on intracellular calcium signaling by duodenal enterocyte in vitro examined in tissues of both human and rat origin. The main findings were as follows: Melatonin is a potent stimulant of duodenal mucosal bicarbonate secretion and also seems to be involved in the acid-induced stimulation of the secretion. Stimulation elicited in the central nervous system by the alpha1-adrenoceptor agonist phenylephrine induced release of melatonin from the intestinal mucosa and a four-fold increase in alkaline secretion. The melatonin antagonist luzindole abolished the duodenal secretory response to administered melatonin and to central nervous phenylephrine but did not influence the release of intestinal melatonin. Central nervous stimulation was also abolished by synchronous ligation of the vagal trunks and the sympathetic chains at the sub-laryngeal level. Melatonin induced release of calcium from intracellular stores and also influx of extracellular calcium in isolated duodenal enterocytes. Enterocytes in clusters functioned as a syncytium. Overnight fasting rapidly and profoundly down-regulated the responses to the duodenal secretagogue orexin-A and the muscarinic agonist bethanechol but not those to melatonin or vasoactive intestinal polypeptide. PMID:16075893

  8. Evaluation through literature data on standardized ileal digestibility and basal ileal endogenous loss of amino acids associated with barley in pigs.

    PubMed

    Spindler, H K; Mosenthin, R; Eklund, M

    2014-10-01

    This meta-analysis aimed to estimate the standardized ileal digestibility (SID) and the basal ileal endogenous amino acid losses (IAAend) in barley for growing pigs. In total, 38 different barley treatments published in 26 peer-reviewed papers were used for the meta-analysis containing information on dietary composition including amino acid (AA) contents of the assay diets, and (or) barley samples, as well as apparent ileal digestibility (AID) of AA in barley. The SID of AA was determined by either correcting AID of AA for their IAAend or by regression analysis between the apparent ileal digestible and total dietary AA contents. The SID values obtained by correcting the AID values for their IAAend amounted to 70%, 77%, 74% and 63% for Lys, Met, Thr and Trp, whereas those based on regression analysis method were 82%, 82%, 69% and 55%, respectively. Estimates of basal ileal endogenous loss of CP in ileal digesta varied considerably and averaged 11.84 g/kg dry matter intake (DMI), whereas IAAend for indispensable AA ranged from 0.05 g/kg DMI for Trp to 1.90 g/kg DMI for Leu. In most cases, these estimates were considerably higher than previously reported values for IAAend. The results of the present regression analysis indicate for most AA higher SID values compared with SID of most AA that were obtained by correcting AID values for IAAend. In view of the observed high variations in IAAend and the low CP content of the barley samples, estimating SID of AA based on literature data by means of the regression method may improve accuracy of SID coefficients for barley. In contrast, transformation of AID values into their corresponding SID values by using a constant correction factor for IAAend adds an additional source of error, thereby reducing the precision in estimating SID of AA. PMID:24923302

  9. The Ileal Lipid Binding Protein Is Required for Efficient Absorption and Transport of Bile Acids in the Distal Portion of the Murine Small Intestine

    PubMed Central

    Praslickova, Dana; Torchia, Enrique C.; Sugiyama, Michael G.; Magrane, Elijah J.; Zwicker, Brittnee L.; Kolodzieyski, Lev; Agellon, Luis B.

    2012-01-01

    The ileal lipid binding protein (ilbp) is a cytoplasmic protein that binds bile acids with high affinity. However evidence demonstrating the role of this protein in bile acid transport and homeostasis is missing. We created a mouse strain lacking ilbp (Fabp6?/? mice) and assessed the impact of ilbp deficiency on bile acid homeostasis and transport in vivo. Elimination of ilbp increased fecal bile acid excretion (54.2%, P<0.05) in female but not male Fabp6?/? mice. The activity of cholesterol 7?-hydroxylase (cyp7a1), the rate-controlling enzyme of the classical bile acid biosynthetic pathway, was significantly increased in female (63.5%, P<0.05) but not in male Fabp6?/? mice. The amount of [3H]taurocholic acid (TCA) excreted by 24 h after oral administration was 102% (P<0.025) higher for female Fabp6?/? mice whereas it was 57.3% (P<0.01) lower for male Fabp6?/? mice, compared to wild-type mice. The retained fraction of the [3H]TCA localized in the small and large intestines was increased by 22% (P<0.02) and decreased by 62.7% (P<0.01), respectively, in male Fabp6?/? mice relative wild-type mice, whereas no changes were seen in female Fabp6?/? mice. Mucosal to serosal bile acid transport using everted distal gut sacs was decreased by 74% (P<0.03) in both sexes of Fabp6?/? mice as compared to wild-type mice. The results demonstrate that ilbp is involved in the apical to basolateral transport of bile acids in ileal enterocytes, and is vital for the maintenance of bile acid homeostasis in the enterohepatic circulation (EHC) in mice. PMID:23251388

  10. 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

  11. Antioxidant action of glutathione and the ascorbic acid/glutathione pair in a model white wine.

    PubMed

    Sonni, Francesca; Clark, Andrew C; Prenzler, Paul D; Riponi, Claudio; Scollary, Geoffrey R

    2011-04-27

    Glutathione was assessed individually, and in combination with ascorbic acid, for its ability to act as an antioxidant with respect to color development in an oxidizing model white wine system. Glutathione was utilized at concentrations normally found in wine (30 mg/L), as well as at concentrations 20-fold higher (860 mg/L), the latter to afford ascorbic acid (500 mg/L) to glutathione ratios of 1:1. The model wine systems were stored at 45 °C without sulfur dioxide and at saturated oxygen levels, thereby in conditions highly conducive to oxidation. Under these conditions the results demonstrated the higher concentration of glutathione could initially provide protection against oxidative coloration, but eventually induced color formation. In the period during which glutathione offered a protective effect, the production of xanthylium cation pigment precursors and o-quinone-derived phenolic compounds was limited. When glutathione induced coloration, polymeric pigments were formed, but these were different from those found in model wine solutions without glutathione. In the presence of ascorbic acid, high concentrations of glutathione were able to delay the decay in ascorbic acid and inhibit the reaction of ascorbic acid degradation products with the wine flavanol compound (+)-catechin. However, on depletion, the glutathione again induced the production of a range of different polymeric pigments. These results highlight new mechanisms through which glutathione can offer both protection and spoilage during the oxidative coloration of a model wine. PMID:21384873

  12. Corneal endothelial glutathione after photodynamic change

    SciTech Connect

    Hull, D.S.; Riley, M.V.; Csukas, S.; Green, K.

    1982-03-01

    Rabbit corneal endothelial cells perfused with 5 X 10(-6)M rose bengal and exposed to incandescent light demonstrated no alteration of either total of or percent oxidized glutathione after 1 hr. Addition of 5400 U/ml catalase to the perfusing solution had no effect on total glutathione levels but caused a marked reduction in percent oxidized glutathione in corneas exposed to light as well as in those not exposed to light. Substitution of sucrose for glucose in the perfusing solution had no effect on total or percent oxidized glutathione. Perfusion of rabbit corneal endothelium with 0.5 mM chlorpromazine and exposure to ultraviolet (UV) light resulted in no change in total glutathione content. A marked reduction in percent oxidized glutathione occurred, however, in corneas perfused with 0.5 mM chlorpromazine both in the presence and absence of UV light. It is concluded that photodynamically induced swelling of corneas is not the result of a failure of the glutathione redox system.

  13. Oral mucositis in myelosuppressive cancer therapy.

    PubMed

    Epstein, J B; Schubert, M M

    1999-09-01

    Because the etiology of mucositis is multifactorial , approaches to prevention and management have also been multifactorial. Effective prevention and management of mucositis will reduce the pain and suffering experienced during cancer treatment. Oropharyngeal pain in cancer patients frequently requires systemic analgesics, adjunctive medications, physical therapy, and psychologic therapy in addition to oral care and topical treatments. Good oral hygiene reduces the severity of oral mucositis and does not increase the risk of bacteremia. Current approaches to management include frequent oral rinsing with saline or bicarbonate rinses, maintaining excellent oral hygiene, and using topical anesthetics and analgesics. Cryotherapy is a potential adjunctive approach in some cases. There are a number of approaches that appear to represent viable candidates for further study. Biologic response modifiers offer the potential for prevention and for acceleration of healing. Various cytokines will enter clinical trials in the near future; these offer the potential for reduction of epithelial cell sensitivity to the toxic effects of cancer therapy or for stimulation of repair of the damaged tissue. Other approaches include the use of medications to reduce exposure of the oral mucosa to chemotherapeutic drugs that are secreted in saliva. Antimicrobial approaches have met with conflicting results, little effect being seen with chlorhexidine and systemic antimicrobials in the prevention of mucositis in radiation patients. In patients with BMT and patients with leukemia, chlorhexidine may not be effective in preventing mucositis, although there may be reduction in oral colonization by Candida. Initial studies of topical antimicrobials that affect the gram-negative oral flora have shown reductions in ulcerative mucositis during radiation therapy but have not been assessed in leukemia/BMT. Among other approaches that require further study are low-energy lasers and anti-inflammatory medications. These approaches to management have undergone initial study, but additional investigation is needed to determine their effectiveness with respect to the prevention of mucositis and symptom management and to determine appropriate doses and frequencies of intervention. Current studies and our increasing understanding of the pathogenesis of oral mucositis will lead to new approaches to management and improved quality of life for these patients. PMID:10503852

  14. Primary bile acid diarrhoea without an ileal carrier defect: quantification of active bile acid transport across the ileal brush border membrane.

    PubMed Central

    van Tilburg, A J; de Rooij, F W; van den Berg, J W; van Blankenstein, M

    1991-01-01

    Unexplained bile acid malabsorption associated with diarrhoea that responds to cholestyramine was first described in 1973 but convincing evidence of the proposed mechanism--a defective active ileal bile acid transport--has never been substantiated. Active bile acid transport was quantified in vitro using brush border membrane vesicles prepared from terminal ileal biopsy specimens from 10 patients who fulfilled the criteria of idiopathic bile acid diarrhoea. They were recruited from 181 patients with bile acid malabsorption of various causes. Transport was quantified as in vitro Na+ dependent bile acid transport (INBAT), expressed as pmol taurocholate/mg brush border membrane protein/15 seconds, and in vitro Na+ dependent bile acid local transport capacity (INBALTC), expressed as pmol taurocholate/g ileal biopsy tissue/15 seconds. The lowest INBAT and INBALTC values in the 10 patients with idiopathic bile acid diarrhoea were well above the 10th centile values of a control group of 132 patients. Both INBAT (mean (range) 88 (30-136)) and INBALTC (158 (85-268)) values were significantly higher in the 10 patients than in the control group (INBAT: mean (range) 63 (1-244), INBALTC: mean (range) 98 (1-408)). Quantification of active ileal bile acid transport in these 10 patients with idiopathic bile acid malabsorption suggests that a genetic (carrier) defect is rare in adults. PMID:2040472

  15. Comparative duodenal, jejunal and ileal responses to luminal saline load.

    PubMed

    Chikh-Issa, A R; Charpin, G; Dumas, C; Nicol, P; Pansu, D; Descroix-Vagne, M

    1993-01-01

    Intestinal ionic exchanges were studied in rat duodenal, jejunal and ileal ligated loops in response to different luminal saline loads: NaCl concentration varied from 150-0 mM, solutions being made isoosmotic with mannitol. The contact delay was 60 min. An exponential relationship was found between water, Na and Cl movements and the initial saline concentration. Maximal absorption was obtained with 150 mM NaCl, and was significantly higher in the duodenum than in the jejunum and ileum. The NaCl concentration for which water, Na, and Cl movements were null was approximately 70 mM NaCl in the duodenum and jejunum, 41 mM for Na and 18 mM for Cl in the ileum. The water efflux induced by the 0-mM NaCl test solution was maximal in the duodenum (1.5 +/- 0.2 ml/h) and decreased in the jejunum (0.8 +/- 0.1 ml/h) and ileum (0.3 +/- 0.1 ml/h) as did sodium, chloride and non-chloride anion efflux. These data support the functional heterogeneity of the small intestine regulating the water and ion exchange in response to luminal saline load, the main difference being connected with the efflux capacity of the mucosa, decreasing from the duodenum to the jejunum and ileum. PMID:8363739

  16. Glutathione, Glutathione-Related Enzymes, and Catalase Activities in the Earthworm Eisenia fetida andrei

    Microsoft Academic Search

    M. Saint-Denis; F. Labrot; J. F. Narbonne; D. Ribera

    1998-01-01

    .   The aim of this work was to provide basic data on the antioxidant defences in the annelid Eisenia fetida andrei (E. f. a.). Methods for measurement of three antioxidant enzymes—catalase (CAT), glutathione peroxidase (GPX), and glutathione\\u000a reductase (GR)—and of glutathione-S-transferase (GST) were optimized. GPX activity differed according to the substrate used:\\u000a cumene hydroperoxide (CUOOH) or hydrogen peroxide (H2O2). The

  17. Glutathione in Cancer Cell Death

    PubMed Central

    Ortega, Angel L.; Mena, Salvador; Estrela, Jose M.

    2011-01-01

    Glutathione (L-?-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy. PMID:24212662

  18. Glutathione Efflux and Cell Death

    PubMed Central

    2012-01-01

    Abstract Significance: Glutathione (GSH) depletion is a central signaling event that regulates the activation of cell death pathways. GSH depletion is often taken as a marker of oxidative stress and thus, as a consequence of its antioxidant properties scavenging reactive species of both oxygen and nitrogen (ROS/RNS). Recent Advances: There is increasing evidence demonstrating that GSH loss is an active phenomenon regulating the redox signaling events modulating cell death activation and progression. Critical Issues: In this work, we review the role of GSH depletion by its efflux, as an important event regulating alterations in the cellular redox balance during cell death independent from oxidative stress and ROS/RNS formation. We discuss the mechanisms involved in GSH efflux during cell death progression and the redox signaling events by which GSH depletion regulates the activation of the cell death machinery. Future Directions: The evidence summarized here clearly places GSH transport as a central mechanism mediating redox signaling during cell death progression. Future studies should be directed toward identifying the molecular identity of GSH transporters mediating GSH extrusion during cell death, and addressing the lack of sensitive approaches to quantify GSH efflux. Antioxid. Redox Signal. 17, 1694–1713. PMID:22656858

  19. Impaired Glutathione Synthesis in Neurodegeneration

    PubMed Central

    Aoyama, Koji; Nakaki, Toshio

    2013-01-01

    Glutathione (GSH) was discovered in yeast cells in 1888. Studies of GSH in mammalian cells before the 1980s focused exclusively on its function for the detoxication of xenobiotics or for drug metabolism in the liver, in which GSH is present at its highest concentration in the body. Increasing evidence has demonstrated other important roles of GSH in the brain, not only for the detoxication of xenobiotics but also for antioxidant defense and the regulation of intracellular redox homeostasis. GSH also regulates cell signaling, protein function, gene expression, and cell differentiation/proliferation in the brain. Clinically, inborn errors in GSH-related enzymes are very rare, but disorders of GSH metabolism are common in major neurodegenerative diseases showing GSH depletion and increased levels of oxidative stress in the brain. GSH depletion would precipitate oxidative damage in the brain, leading to neurodegenerative diseases. This review focuses on the significance of GSH function, the synthesis of GSH and its metabolism, and clinical disorders of GSH metabolism. A potential approach to increase brain GSH levels against neurodegeneration is also discussed. PMID:24145751

  20. Evidence-based oral care for oral mucositis.

    PubMed

    Farrington, Michele; Cullen, Laura; Dawson, Cindy

    2013-01-01

    Nurses must intervene to provide evidence-based supportive care and symptom management for cancer patients. Oral mucositis, a distressing side effect of cancer treatment, is both a research and clinical priority. Nurses can lead improvements with evidence-based oral mucositis interventions. This article describes application of evidence-based clinical recommendations for oral mucositis across diverse patient populations. PMID:24069711

  1. Apathogenic, intestinal, segmented, filamentous bacteria stimulate the mucosal immune system of mice.

    PubMed Central

    Klaasen, H L; Van der Heijden, P J; Stok, W; Poelma, F G; Koopman, J P; Van den Brink, M E; Bakker, M H; Eling, W M; Beynen, A C

    1993-01-01

    Segmented filamentous bacteria (SFBs) are apathogenic autochthonous bacteria in the murine small intestine that preferentially attach to Peyer's patch epithelium. SFBs have never been cultured in vitro. We have studied the effects of SFBs on the immune system of the host. Mice monoassociated with SFBs were compared with germ-free mice and with mice without SFBs but with a specific-pathogen-free (SPF) gut flora. SFBs versus no microbial flora raised the number of lymphoid cells in the lamina propria of the ileal and cecal mucosa, raised the number of immunoglobulin A (IgA)-secreting cells in the intestinal mucosa, produced elevated IgA titers in serum and intestinal secretions, and enhanced the concanavalin A-induced proliferative responses of mesenteric lymph node cells. The SPF flora had effects similar to but less pronounced than those mediated by SFBs. The results indicate that SFBs stimulate the mucosal immune system to a greater extent than do other autochthonous gut bacteria. PMID:8418051

  2. Strategies of mucosal immunotherapy for allergic diseases

    Microsoft Academic Search

    Yi-Ling Ye; Ya-Hui Chuang; Bor-Luen Chiang; B-L Chiang

    2011-01-01

    Incidences of allergic disease have recently increased worldwide. Allergen-specific immunotherapy (SIT) has long been a controversial treatment for allergic diseases. Although beneficial effects on clinically relevant outcomes have been demonstrated in clinical trials by subcutaneous immunotherapy (SCIT), there remains a risk of severe and sometimes fatal anaphylaxis. Mucosal immunotherapy is one advantageous choice because of its non-injection routes of administration

  3. Pediatric food allergy and mucosal tolerance

    Microsoft Academic Search

    A M Scurlock; B P Vickery; J O'B Hourihane; A W Burks

    2010-01-01

    The gastrointestinal (GI) mucosal immune response is characterized by an intricate balance between host defense and immunoregulation. A principal element of this normal response is acquisition of oral tolerance. Aberrations in oral tolerance induction can lead to food allergy, an increasingly prevalent disorder that causes significant medical and psychosocial stressors for patients and families. At present there is no definitive

  4. Tracheal reconstruction: mucosal survival on porous titanium

    Microsoft Academic Search

    L. M. C. Janssen; J. P. Li; N. Kops; K. de Groot; J. W. von den Hoff; L. Feenstra; J. A. U. Hardillo

    2009-01-01

    OBJECTIVE: To investigate whether porous titanium can provide a better support for revascularization of a mucosal graft ideal for tracheal reconstruction. In patients with laryngotracheal stenosis or tumor, the mucosa with supporting structures can be damaged, resulting in a defect that has to be reconstructed. Autologous tissues like cartilage and mucosa have been used for reconstruction. The main problem has

  5. Mechanisms of Neonatal Mucosal Antibody Protection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Following an abrupt transition at birth from the sterile uterus to an environment with abundant commensal and pathogenic microbes, neonatal mammals are protected by maternal antibodies at mucosal surfaces. We show in mice that different antibody isotypes work in distinct ways to protect the neonatal...

  6. The mucosal firewalls against commensal intestinal microbes

    Microsoft Academic Search

    Andrew J. Macpherson; Emma Slack; Markus B. Geuking; Kathy D. McCoy

    2009-01-01

    Mammals coexist with an extremely dense microbiota in the lower intestine. Despite the constant challenge of small numbers\\u000a of microbes penetrating the intestinal surface epithelium, it is very unusual for these organisms to cause disease. In this\\u000a review article, we present the different mucosal firewalls that contain and allow mutualism with the intestinal microbiota.

  7. The effect of N-acetyl-L-cysteine on the viscosity of ileal neobladder mucus.

    PubMed

    Schrier, B P; Lichtendonk, W J; Witjes, J A

    2002-05-01

    N-acetyl-L-cysteine (NAC) proved to be an effective mucolytic in pulmonary secretions. Our goal was to investigate the in vitro effect of NAC on viscosity of ileal neobladder mucus. The urine of a patient with an ileal neobladder was collected during the first 7 days postoperatively and stored in a refrigerator. After precipitation, the urine was decanted. The residue was stirred to a homogeneous suspension. To samples of 4.5 ml mucus, 0.5 ml NAC 10% was added. To the control sample, 0.5 ml water was added. The samples were incubated in a water bath at 37 degrees C for 5, 30 and 60 min. Viscosity was measured in the Bohlin VOR Rheometer. The viscosity of the ileal neobladder mucus decreased quickly after incubating with NAC 10%. Viscosity increased slightly after I h of incubation. The viscosity in the control sample was higher than in the other incubated samples. NAC was found to decrease the viscosity of ileal neobladder mucus, supporting the in vivo experience that NAC can be useful in patients with an ileal neobladder to facilitate the evacuation of mucus by decreasing viscosity. PMID:12088194

  8. Intracellular glutathione pools are heterogeneously concentrated.

    PubMed

    Montero, Davide; Tachibana, Christine; Rahr Winther, Jakob; Appenzeller-Herzog, Christian

    2013-01-01

    Glutathione is present in millimolar concentrations in the cell, but its relative distribution among cellular compartments remains elusive. We have chosen the endoplasmic reticulum (ER) as an example organelle to study compartment-specific glutathione levels. Using a glutaredoxin sensor (sCGrx1pER), which rapidly and specifically equilibrates with the reduced glutathione (GSH)-glutathione disulfide (GSSG) redox couple with known equilibrium constant, we showed that the [GSH]:[GSSG] ratio in the ER of intact HeLa cells is less than 7:1. Taking into consideration the previously determined value for [GSH](2):[GSSG] in the ER of 83 mM, this translates into a total glutathione concentration in the ER ([GStot]=[GSH]+2[GSSG]) of greater than 15 mM. Since the integrated, intracellular [GStot] was measured as ~7 mM, we conclude the existence of a [GStot] gradient across the ER membrane. A possible homeostatic mechanism by which cytosol-derived glutathione is trapped in the ER is discussed. We propose a high [GStot] as a distinguishing feature of the ER environment compared to the extracellular space. PMID:24251119

  9. Topical/mucosal delivery of sub-unit vaccines that stimulate the ocular mucosal immune system.

    PubMed

    Nesburn, Anthony B; Bettahi, Ilham; Zhang, Xiuli; Zhu, Xiaoming; Chamberlain, Winston; Afifi, Rasha E; Wechsler, Steven L; BenMohamed, Lbachir

    2006-10-01

    Mucosal vaccination is proving to be one of the greatest challenges in modern vaccine development. Although ocular mucosal immunity is highly beneficial for achieving protective immunity, the induction of ocular mucosal immunity against ocular infectious pathogens, particularly herpes simplex virus type 1 (HSV-1), which is the leading cause of infectious corneal blindness, remains difficult. Recent developments in cellular and molecular immunology of the ocular mucosal immune system (OMIS) may help in the design of more effective and optimal immunization strategies against ocular pathogens. In this review, we highlight ocular mucosal immunoprophylactic and immunotherapeutic vaccine strategies that have been evaluated to control the many pathogens that attack the surface of the eye. Next, we describe the current understandings of the OMIS and elucidate the structure and the function of the humoral and cellular immune system that protects the surface of the eye. Results from our recent experiments using topical ocular delivery of peptides-CpG and lipopeptide-based vaccines against HSV-1 infection are presented. The future challenges and issues related to the ocular mucosal delivery of molecularly defined sub-unit vaccines are discussed. PMID:17146573

  10. Ultrasonic fragmentation. A new technique for mucosal proctectomy

    SciTech Connect

    Heimann, T.M.; Kurtz, R.J.; Aufses, A.H. Jr.

    1985-10-01

    A new technique is reported for mucosal proctectomy that does not require manual separation of the mucosa and submucosa from the underlying muscularis. Mucosal proctectomy using ultrasonic fragmentation of the rectal mucosa was performed in four patients. Three had severe ulcerative colitis, and one patient had radiation proctitis with a rectal stricture. In all cases an endorectal pullthrough with anastomosis to the area of the dentate line was performed. Healing after ultrasonic mucosal proctectomy occurred without infection or retraction. Ultrasonic fragmentation offers an alternative to the standard technique of mucosal proctectomy. This new method is useful in those patients in whom separation of the rectal mucosal layer is difficult to perform.

  11. Inhibition of the effect of serotonin on rat ileal transport by cisapride: evidence in favour of the involvement of 5-HT2 receptors.

    PubMed Central

    Moriarty, K J; Higgs, N B; Woodford, M; Warhurst, G; Turnberg, L A

    1987-01-01

    Cisapride is a synthetic drug which binds, in vitro, to type 2 serotonin receptors. We examined the influence of serotonin and cisapride on ion transport across intestinal mucosa in vitro and studied the effect of cisapride on the response to serotonin. Segments of ileum of male Sprague-Dawley rats were stripped of muscle layers and mounted in flux chambers. The addition of serotonin (10(-8) to 10(-4) M) to the serosal aspect of the mucosa caused a rapid, dose-dependent rise in short circuit current and transmural potential difference. Cisapride alone (5 X 10(-5) M), when added to the mucosal and serosal surfaces, had no effect on the short circuit current, transmural potential difference, resistance, or sodium and chloride fluxes across the mucosa. It did, however, inhibit the response of the mucosa to serotonin (10(-5) M) in a dose dependent manner and blocked it completely at a concentration of 5 X 10(-5) M. Serotonin (5 X 10(-5) M) increased serosal to mucosal flux of chloride from 12.6 +/- 0.8 to 15.2 +/- 0.6 mumol/cm2/h (p less than 0.025), thus reducing net chloride absorption from 4.65 +/- 0.81 to 1.49 +/- 1.04 mumol/cm2/h (p less than 0.05). This effect was completely blocked by cisapride (5 X 10(-5) M). In summary, cisapride inhibits the effect of serotonin on rat ileal ion transport, probably by blocking type 2 serotonin receptors. PMID:3653752

  12. Large Intraluminal Ileal Hematoma Presenting as Small Bowel Obstruction in a Child

    PubMed Central

    Lim, Yun Jung; Nam, So Hyun; Kim, Seon Jeong

    2015-01-01

    Intraluminal small bowel hematoma has been rarely reported in children, as a rare cause of small bowel obstruction. We present a case of an intraluminal ileal hematoma presenting as small bowel obstruction in a child. Computed Tomography (CT) indicated a large intraluminal hyperdense lesion in the distal ileum as the cause of small bowel obstruction. Abdominal ultrasonography (US) showed an echogenic mass-like lesion with multiple septa in the distal ileum. Small bowel obstruction due to a complicated cystic mass was provisionally diagnosed. Histopathologic examination of the resected mass suggested a submucosal ileal hematoma. Although intraluminal small bowel hematoma is rare in children, it can present as an intraluminal cystic mass and should be considered as a rare cause of small bowel obstruction. The US and CT findings of submucosal ileal hematoma could be useful for the diagnosis of such cases in the future. PMID:25901264

  13. [Undiversion in a patient with ileal conduit using cecoileal urinary reservoir, a case report].

    PubMed

    Kashiwagi, A; Satou, S; Machino, R; Chikaraishi, T; Demura, T; Nomomura, K; Togashi, M; Koyanagi, T

    1992-01-01

    A case of urinary undiversion in a 19 year old man with high ileal loop, who at the age of 1 year was inadvertently cystectomized for probable acute urinary retention masquerading as acute abdomen, is reported. The ileo-ceco-colonic segment was isolated and the colon was partially detubularized. After ileocecal intussusception and stabilization to the cecal wall (Hendren), a segment of ileal patch was applied to form an Indiana type pouch. The ileal loop was free from the abdominal wall and its distal end was anastomosed to the terminal ileum of the pouch. Undiversion was completed by connecting the pouch at its dependent portion with the remnant prostatic urethra. At 4 months postoperatively the pouch functions quite satisfactorily as a low pressure and good volume reservoir that empties well without reflux. His erectile and ejaculatory function have also been maintained. PMID:1564831

  14. Dietary N-Carbamylglutamate Supplementation Boosts Intestinal Mucosal Immunity in Escherichia coli Challenged Piglets

    PubMed Central

    Zhang, Fengrui; Zeng, Xiangfang; Yang, Fengjuan; Huang, Zhimin; Liu, Hong; Ma, Xi; Qiao, Shiyan

    2013-01-01

    N-carbamylglutamate (NCG) has been shown to enhance performance in neonatal piglets. However, few studies have demonstrated the effect of NCG on the intestinal mucosal barrier. This study was conducted to determine the effects of dietary NCG supplementation on intestinal mucosal immunity in neonatal piglets after an Escherichia coli (E. coli) challenge. New-born piglets (4 d old) were assigned randomly to one of four treatments (n?=?7), including (I) sham challenge, (II) sham challenge +50 mg/kg NCG, (III) E. coli challenge, and (IV) E. coli challenge +50 mg/kg NCG. On d 8, pigs in the E. coli challenge groups (III and IV) were orally challenged with 5 mL of E. coli K88 (108 CFU/mL), whereas pigs in the sham challenge groups (I and II) were orally dosed with an equal volume of water. On d 13, all piglets were sacrificed, and samples were collected and examined. The results show that average daily gain in the E. coli challenged piglets (III and IV) was decreased (PE.coli<0.05). However, it tended to be higher in the NCG treated piglets (II and IV). Ileum secretory IgA, as well as IFN-?, IL-2, IL-4 and IL-10 in ileal homogenates, were increased in E. coli challenged piglets (III and IV). Similarly, ileum SIgA and IL-10 levels, and CD4+ percentage in NCG treated piglets (II and IV) were higher than no-NCG treated piglets (PNCG<0.05). However, the IL-2 level was only decreased in the piglets of E. coli challenge + NCG group (IV) compared with E. coli challenge group (III) (P<0.05). No change in the IL-2 level of the sham challenged piglets (III) was observed. In conclusion, dietary NCG supplementation has some beneficial effects on intestinal mucosal immunity in E. coli challenged piglets, which might be associated with stimulated lymphocyte proliferation and cytokine synthesis. Our findings have an important implication that NCG may be used to reduce diarrhea in neonatal piglets. PMID:23840434

  15. Daily rhythm of glutathione peroxidase activity, lipid peroxidation and glutathione levels in tissues of pinealectomized rats

    Microsoft Academic Search

    Giyasettin Baydas; M. Ferit Gursu; Seval Yilmaz; Sinan Canpolat; Abdullah Yasar; Gurkan Cikim; Halit Canatan

    2002-01-01

    Melatonin is a component of the antioxidant defense system since it has radical scavenging and antioxidant activities. In the present study, we aimed to investigate the endogenous rhythm of antioxidant enzyme glutathione peroxidase (GSH-Px) activity, oxidized glutathione (GSSG) and lipid peroxidation levels in tissues of pinealectomized rats (PINX). Rats were sacrificed by decapitation at 4 h intervals. GSH-Px activity, GSSG

  16. The Glutathione System of Aspergillus nidulans Involves a Fungus-specific Glutathione S-Transferase*S?

    PubMed Central

    Sato, Ikuo; Shimizu, Motoyuki; Hoshino, Takayuki; Takaya, Naoki

    2009-01-01

    The tripeptide glutathione is involved in cellular defense mechanisms for xenobiotics and reactive oxygen species. This study investigated glutathione-dependent mechanisms in the model organism Aspergillus nidulans. A recombinant dimeric protein of A. nidulans glutathione reductase (GR) contained FAD and reduced oxidized glutathione (GSSG) using NADPH as an electron donor. A deletion strain of the GR gene (glrA) accumulated less intracellular reduced glutathione (GSH), indicating that the fungal GR contributes to GSSG reduction in vivo. Growth of the deletion strain of glrA was temperature-sensitive, and this phenotype was suppressed by adding GSH to the medium. The strain subsequently accumulated more intracellular superoxide, and cell-free respiration activity was partly defective. Growth of the strain decreased in the presence of oxidants, which induced glrA expression 1.5-6-fold. These results indicated that the fungal glutathione system functions as an antioxidant mechanism in A. nidulans. Our findings further revealed an initial proteomic differential display on GR-depleted and wild type strains. Up-regulation of thioredoxin reductase, peroxiredoxins, catalases, and cytochrome c peroxidase in the glrA-deletion strain revealed interplay between the glutathione system and both the thioredoxin system and hydrogen peroxide defense mechanisms. We also identified a hypothetical, up-regulated protein in the GR-depleted strains as glutathione S-transferase, which is unique among Ascomycetes fungi. PMID:19171936

  17. Direct measurement of first-pass ileal clearance of a bile acid in humans

    SciTech Connect

    Galatola, G.; Jazrawi, R.P.; Bridges, C.; Joseph, A.E.; Northfield, T.C. (St. George's Hospital Medical School, London (England))

    1991-04-01

    The purpose of this study was to develop and validate a method of directly measuring ileal bile acid absorption efficiency during a single enterohepatic cycle (first-pass ileal clearance). This has become feasible for the first time because of the availability of the synthetic gamma-labeled bile acid 75Selena-homocholic acid-taurine (75SeHCAT). Together with the corresponding natural bile acid cholic acid-taurine (labeled with 14C), SeHCAT was infused distal to an occluding balloon situated beyond the ampulla of Vater in six healthy subjects. Completion of a single enterohepatic cycle was assessed by obtaining a plateau for 75SeHCAT activity proximal to the occluding balloon, which prevented further cycles. Unabsorbed 75SeHCAT was collected after total gut washout, which was administered distal to the occluding balloon. 75SeHCAT activity in the rectal effluent measured by gamma counter was compared with that of absorbed 75SeHCAT level measured by gamma camera and was used to calculate first-pass ileal clearance. This was very efficient (mean value, 96%) and showed very little variation in the six subjects studied (range, 95%-97%). A parallel time-activity course in hepatic bile for 14C and 75Se during a single enterohepatic cycle, together with a ratio of unity for 14C/75Se in samples obtained at different time intervals, suggests that 75SeHCAT is handled by the ileum like the natural bile acid cholic acid-taurine. Extrapolation of 75SeHCAT first-pass ileal clearance to that of the natural bile acid therefore seems justifiable. In a subsidiary experiment, ileal absorption efficiency per day for 75SeHCAT was also measured by scanning the gallbladder area on 5 successive days after the measurement of first-pass ileal clearance. In contrast with absorption efficiency per cycle, absorption efficiency per day varied widely (49%-86%).

  18. Combined treatment with dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin and elemental diets reduced indomethacin-induced intestinal injury in rats via the increase of mucosal glucagon-like peptide-2 concentration

    PubMed Central

    Fujiwara, Kaori; Inoue, Takuya; Yorifuji, Naoki; Iguchi, Munetaka; Sakanaka, Taisuke; Narabayashi, Ken; Kakimoto, Kazuki; Nouda, Sadaharu; Okada, Toshihiko; Ishida, Kumi; Abe, Yosuke; Masuda, Daisuke; Takeuchi, Toshihisa; Fukunishi, Shinya; Umegaki, Eiji; Akiba, Yasutada; Kaunitz, Jonathan D.; Higuchi, Kazuhide

    2015-01-01

    The gut incretin glucagon-like peptide-1 (GLP-1) and the intestinotropic hormone GLP-2 are released from enteroendocrine L cells in response to ingested nutrients. Treatment with an exogenous GLP-2 analogue increases intestinal villous mass and prevents intestinal injury. Since GLP-2 is rapidly degraded by dipeptidyl peptidase 4 (DPP4), DPP4 inhibition may be an effective treatment for intestinal ulcers. We measured mRNA expression and DPP enzymatic activity in intestinal segments. Mucosal DPP activity and GLP concentrations were measured after administration of the DPP4 inhibitor sitagliptin (STG). Small intestinal ulcers were induced by indomethacin (IM) injection. STG was given before IM treatment, or orally administered after IM treatment with or without an elemental diet (ED). DPP4 mRNA expression and enzymatic activity were high in the jejunum and ileum. STG dose-dependently suppressed ileal mucosal enzyme activity. Treatment with STG prior to IM reduced small intestinal ulcer scores. Combined treatment with STG and ED accelerated intestinal ulcer healing, accompanied by increased mucosal GLP-2 concentrations. The reduction of ulcers by ED and STG was reversed by co-administration of the GLP-2 receptor antagonist. DPP4 inhibition combined with luminal nutrients, which up-regulate mucosal concentrations of GLP-2, may be an effective therapy for the treatment of small intestinal ulcers. PMID:25759522

  19. Combined treatment with dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin and elemental diets reduced indomethacin-induced intestinal injury in rats via the increase of mucosal glucagon-like peptide-2 concentration.

    PubMed

    Fujiwara, Kaori; Inoue, Takuya; Yorifuji, Naoki; Iguchi, Munetaka; Sakanaka, Taisuke; Narabayashi, Ken; Kakimoto, Kazuki; Nouda, Sadaharu; Okada, Toshihiko; Ishida, Kumi; Abe, Yosuke; Masuda, Daisuke; Takeuchi, Toshihisa; Fukunishi, Shinya; Umegaki, Eiji; Akiba, Yasutada; Kaunitz, Jonathan D; Higuchi, Kazuhide

    2015-03-01

    The gut incretin glucagon-like peptide-1 (GLP-1) and the intestinotropic hormone GLP-2 are released from enteroendocrine L cells in response to ingested nutrients. Treatment with an exogenous GLP-2 analogue increases intestinal villous mass and prevents intestinal injury. Since GLP-2 is rapidly degraded by dipeptidyl peptidase 4 (DPP4), DPP4 inhibition may be an effective treatment for intestinal ulcers. We measured mRNA expression and DPP enzymatic activity in intestinal segments. Mucosal DPP activity and GLP concentrations were measured after administration of the DPP4 inhibitor sitagliptin (STG). Small intestinal ulcers were induced by indomethacin (IM) injection. STG was given before IM treatment, or orally administered after IM treatment with or without an elemental diet (ED). DPP4 mRNA expression and enzymatic activity were high in the jejunum and ileum. STG dose-dependently suppressed ileal mucosal enzyme activity. Treatment with STG prior to IM reduced small intestinal ulcer scores. Combined treatment with STG and ED accelerated intestinal ulcer healing, accompanied by increased mucosal GLP-2 concentrations. The reduction of ulcers by ED and STG was reversed by co-administration of the GLP-2 receptor antagonist. DPP4 inhibition combined with luminal nutrients, which up-regulate mucosal concentrations of GLP-2, may be an effective therapy for the treatment of small intestinal ulcers. PMID:25759522

  20. Mucosal immunity: its role in defense and allergy.

    PubMed

    Tlaskalová-Hogenová, Helena; Tucková, Ludmila; Lodinová-Zádniková, Rája; Stepánková, Renata; Cukrowska, Bozena; Funda, David P; Striz, Ilja; Kozáková, Hana; Trebichavský, Ilja; Sokol, Dan; Reháková, Zuzana; Sinkora, Jirí; Fundová, Petra; Horáková, Dana; Jelínková, Lenka; Sánchez, Daniel

    2002-06-01

    The interface between the organism and the outside world, which is the site of exchange of nutrients, export of products and waste components, must be selectively permeable and at the same time, it must constitute a barrier equipped with local defense mechanisms against environmental threats (e.g. invading pathogens). The boundaries with the environment (mucosal and skin surfaces) are therefore covered with special epithelial layers which support this barrier function. The immune system, associated with mucosal surfaces covering the largest area of the body (200-300 m(2)), evolved mechanisms discriminating between harmless antigens and commensal microorganisms and dangerous pathogens. The innate mucosal immune system, represented by epithelial and other mucosal cells and their products, is able to recognize the conserved pathogenic patterns on microbes by pattern recognition receptors such as Toll-like receptors, CD14 and others. As documented in experimental gnotobiotic models, highly protective colonization of mucosal surfaces by commensals has an important stimulatory effect on postnatal development of immune responses, metabolic processes (e.g. nutrition) and other host activities; these local and systemic immune responses are later replaced by inhibition, i.e. by induction of mucosal (oral) tolerance. Characteristic features of mucosal immunity distinguishing it from systemic immunity are: strongly developed mechanisms of innate defense, the existence of characteristic populations of unique types of lymphocytes, colonization of the mucosal and exocrine glands by cells originating from the mucosal organized tissues ('common mucosal system') and preferential induction of inhibition of the responses to nondangerous antigens (mucosal tolerance). Many chronic diseases, including allergy, may occur as a result of genetically based or environmentally induced changes in mechanisms regulating mucosal immunity and tolerance; this leads to impaired mucosal barrier function, disturbed exclusion and increased penetration of microbial, food or airborne antigens into the circulation and consequently to exaggerated and generalized immune responses to mucosally occurring antigens, allergens, superantigens and mitogens. PMID:12065907

  1. Forgotten DJ Stent with a Large Calculus at Its Distal End in an Ileal Conduit Diversion

    PubMed Central

    Puri, Anurag; Priyadarshi, Vinod; Raizada, Nivedita; Pal, Dilip Kumar

    2014-01-01

    Calculus formation in an ileal conduit following cystectomy is a known complication. Encrustation and formation of calculus may also occur over a DJ stent retained for a long period; but this is never reported in patients with conduit diversion because of close surveillance of these patients. Here we report first case of a large calculus encrusted over a forgotten DJ stent within an ileal conduit in a man who had undergone urinary diversion following radical cystectomy for carcinoma urinary bladder 8 years earlier. PMID:25215257

  2. Pediatric food allergy and mucosal tolerance.

    PubMed

    Scurlock, A M; Vickery, B P; Hourihane, J O'B; Burks, A W

    2010-07-01

    The gastrointestinal (GI) mucosal immune response is characterized by an intricate balance between host defense and immunoregulation. A principal element of this normal response is acquisition of oral tolerance. Aberrations in oral tolerance induction can lead to food allergy, an increasingly prevalent disorder that causes significant medical and psychosocial stressors for patients and families. At present there is no definitive therapy for food allergy and the mainstays of treatment are allergen avoidance, nutritional support, and ready access to emergency medications. Significant progress toward an active therapy for food allergy has been made with the advent of novel therapies such as oral immunotherapy (OIT) and sublingual immunotherapy (SLIT), which modulate the GI mucosal immune response with the goal of promoting oral tolerance. In this review, we will examine the mechanisms of oral tolerance induction and its relation to food allergy and explore novel immunotherapeutic strategies for treatment and prevention of food allergy. PMID:20505663

  3. Mechanical endonasal dacryocystorhinostomy with mucosal flaps

    PubMed Central

    Tsirbas, A; Wormald, P J

    2003-01-01

    Aims: To describe and assess the efficacy of mechanical endonasal dacryocystorhinostomy (MENDCR). This is a new technique that involves creation of a large rhinostomy and mucosal flaps. The study involved a prospective non-randomised interventional case series with short perioperative follow up. Method: A prospective series of 104 consecutive endonasal DCRs performed from January 1999 to December 2001 were entered into the study. Patients included in the study had nasolacrimal duct obstruction and had not had previous lacrimal surgery. The technique involved anastomosis of nasal mucosal and lacrimal sac flaps and a large bony ostium. Surgery was performed by two surgeons (AT/PJW). Follow up assessment included nasoendoscopy as well as symptom evaluation. Success was defined as anatomical patency with fluorescein flow on nasoendoscopy and patency to lacrimal syringing. The average follow up time was 9.7 months (range 2–28, SD 6.7 months). Results: There were 104 DCRs performed on 86 patients (30 male, 56 female). The average age of the patients was 59 years (range 3–89, SD 24.1 years). Common presentations were epiphora (77%) and/or mucocele (19%). Septoplasty (SMR) was required in 48 DCRs (46%) and 13 DCRs (12.5%) needed other endoscopic surgery in conjunction with the lacrimal surgery. The surgery was successful in 93 cases (89%). Of the 11 cases that were classified as a failure six patients was anatomically patent but still symptomatic and another two had preoperative canalicular problems. The anatomical patency with this new technique was thus 95% (99 of 104 DCRs). Conclusion: MENDCR involves creation of a large ostium and mucosal preservation for the construction of flaps. The anatomical success is 95% and is similar to external DCR and better then other endonasal approaches. The authors suggest that creation of a large ostium as well as mucosal flaps improves the efficacy of this endonasal technique. PMID:12488261

  4. Total colectomy, mucosal proctectomy, and ileoanal anastomosis

    Microsoft Academic Search

    J. Utsunomiya; T. Iwama; M. Imajo; S. Matsuo; S. Sawai; K. Yaegashi; R. Hirayama

    1980-01-01

    A safe and practical procedure for total colectomy and mucosal proctectomy with ileonal anastomosis has been developed and\\u000a performed by us on 11 patients with adenomatosis coli and two patients with ulcerative colitis. The major features of the\\u000a operative procedure are 1) total removal of the rectal mucosa to just above the dentate line; 2) preservation of anorectal\\u000a function by

  5. Effects of lactoferrin supplementation on ileal and total tract nutrient digestibility, gastrointestinal microbial populations, and immune characteristics of ileal cannulated, healthy, adult dogs

    Microsoft Academic Search

    Lynda L. Pope; Elizabeth A. Flickinger; Lisa K. Karr-Lilienthal; Julie K. Spears; Stephanie Krammer; George C. Fahey Jr

    2006-01-01

    Orally supplemented lactoferrin derived from bovine milk is purported to have beneficial effects on gut health of animals. Bovine lactoferrin (0, 60, or 120 mg\\/d) was fed to ileal cannulated, adult dogs in a replicated 3 × 3 Latin square design with 14 d periods. Control dogs tended (p = 0.06) to have higher fecal DM concentrations compared with dogs supplemented with 120 mg\\/d lactoferrin (34.5

  6. Protective Effects of the Traditional Herbal Formula Oryeongsan Water Extract on Ethanol-Induced Acute Gastric Mucosal Injury in Rats

    PubMed Central

    Jeon, Woo-Young; Lee, Mee-Young; Shin, In-Sik; Lim, Hye-Sun; Shin, Hyeun-Kyoo

    2012-01-01

    This study was performed to evaluate the protective effect and safety of Oryeongsan water extract (OSWE) on ethanol-induced acute gastric mucosal injury and an acute toxicity study in rats. Acute gastric lesions were induced via intragastric oral administration of absolute ethanol at a dose of 5?mL/kg. OSWE (100 and 200?mg/kg) was administered to rats 2?h prior to the oral administration of absolute ethanol. The stomach of animal models was opened and gastric mucosal lesions were examined. Gastric mucosal injuries were evaluated by measuring the levels of malondialdehyde (MDA), glutathione (GSH), and the activity of antioxidant enzymes. In the acute toxicity study, no adverse effects of OSWE were observed at doses up to 2000?mg/kg/day. Administration of OSWE reduced the damage by conditioning the gastric mucosa against ethanol-induced acute gastric injury, which included hemorrhage, hyperemia, and loss of epithelial cells. The level of MDA was reduced in OSWE-treated groups compared with the ethanol-induced group. Moreover, the level of GSH and the activity of antioxidant enzymes were significantly increased in the OSWE-treated groups. Our findings suggest that OSWE has a protective effect on the gastric mucosa against ethanol-induced acute gastric injury via the upregulation of antioxidant enzymes. PMID:23118790

  7. Glutathione Reductase/Glutathione Is Responsible for Cytotoxic Elemental Sulfur Tolerance via Polysulfide Shuttle in Fungi*

    PubMed Central

    Sato, Ikuo; Shimatani, Kanami; Fujita, Kensaku; Abe, Tsuyoshi; Shimizu, Motoyuki; Fujii, Tatsuya; Hoshino, Takayuki; Takaya, Naoki

    2011-01-01

    Fungi that can reduce elemental sulfur to sulfide are widely distributed, but the mechanism and physiological significance of the reaction have been poorly characterized. Here, we purified elemental sulfur-reductase (SR) and cloned its gene from the elemental sulfur-reducing fungus Fusarium oxysporum. We found that NADPH-glutathione reductase (GR) reduces elemental sulfur via glutathione as an intermediate. A loss-of-function mutant of the SR/GR gene generated less sulfide from elemental sulfur than the wild-type strain. Its growth was hypersensitive to elemental sulfur, and it accumulated higher levels of oxidized glutathione, indicating that the GR/glutathione system confers tolerance to cytotoxic elemental sulfur by reducing it to less harmful sulfide. The SR/GR reduced polysulfide as efficiently as elemental sulfur, which implies that soluble polysulfide shuttles reducing equivalents to exocellular insoluble elemental sulfur and generates sulfide. The ubiquitous distribution of the GR/glutathione system together with our findings that GR-deficient mutants derived from Saccharomyces cerevisiae and Aspergillus nidulans reduced less sulfur and that their growth was hypersensitive to elemental sulfur indicated a wide distribution of the system among fungi. These results indicate a novel biological function of the GR/glutathione system in elemental sulfur reduction, which is distinguishable from bacterial and archaeal mechanisms of glutathione- independent sulfur reduction. PMID:21474441

  8. True ileal digestible trypotophan to lysine ratios in 90 to 125 kg barrows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three experiments were conducted to determine the optimal true ileal digestible (TID) tryptophen:lysime (Trp:Lys) ratio for 90 to 125 kg barrows. Basal diets contained 0.55% TID Lys and were either corn (Exp. 1) or corn-soybean meal (Exp. 2 and 3) based diets supplemented with crystalline amino aci...

  9. Indeterminate colitis predisposes to perineal complications after ileal pouch-anal anastomosis

    Microsoft Academic Search

    Walter A. Koltun; David J. Schoetz; Patricia L. Roberts; John J. Murray; John A. Coller; Malcolm C. Veidenheimer

    1991-01-01

    This study retrospectively evaluated 288 patients who had undergone ileal pouch-anal anastomosis to determine the incidence of perineal complications and to relate these findings to the pathologic diagnosis, with the goal of specifically clarifying the appropriate surgical management of patients with indeterminate colitis. Of these 288 patients, 235 patients (82 percent) had a diagnosis of chronic ulcerative colitis, 18 patients

  10. Long-term results of ileal pouch-anal anastomosis in patients with Crohn's disease

    Microsoft Academic Search

    Peter M. Sagar; Roger R. Dozois; Bruce G. Wolff

    1996-01-01

    PURPOSE: Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for most patients with chronic ulcerative colitis. Crohn's disease is, however, a contraindication. Because distinction between UC and Crohn's disease can be difficult, some patients with Crohn's disease inadvertently undergo IPAA. The aim of this study was to determine the long-term outcome of patients with Crohn's disease who have

  11. Postoperative intra-abdominal and pelvic sepsis complicating ileal pouch-anal anastomosis

    Microsoft Academic Search

    N. A. Scott; R. R. Dozois; R. W. Beart; J. H. Pemberton; B. G. Wolff; D. M. Ilstrup

    1988-01-01

    In a series of 500 patients who underwent ileal pouch-anal anastomosis for ulcerative colitis or polyposis coli, significant intra-abdominal or pelvic sepsis developed in 30 (6%). Among the patients who did not require laparotomy because they responded to treatment with antibiotics or local drainage (surgical or radiologically guided) or both, no pouches were excised and the ileostomy closure rate (92%)

  12. Familial adenomatous polyposis: Results following ileal pouch-anal anastomosis and ileorectostomy

    Microsoft Academic Search

    Wayne L. Ambroze Jr; Roger R. Dozois; John H. Pemberton; Robert W. Beart; Duane M. Ilstrup

    1992-01-01

    To compare the clinical and functional results of ileorectostomy (IR) and ileal pouch-anal anastomosis (IPAA) in patients with familial adenomatous polyposis (FAP), we reviewed the results of 94 IPAA patients and 21 IR patients who were operated upon between 1978 and 1988. The groups were similar with respect to age and sex. None of the patients died postoperatiyely. Postoperative complications

  13. Risk adjustment is crucial in comparing outcomes of various surgical modalities in patients with ileal perforation

    Microsoft Academic Search

    Ravindra Singh Mohil; Tanveer Singh; Satyavrat Arya; Dinesh Bhatnagar

    2008-01-01

    BACKGROUND: Using crude mortality and morbidity rates for comparing outcomes can be misleading. The aim of the present study was to compare the outcome of various surgical modalities without and with risk adjustment using Physiologic and Operative Severity Scoring for the enUmeration of Mortality and morbidity (POSSUM) score in cases of ileal perforations. METHODS: Prospective study on 125 patients of

  14. Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

    PubMed Central

    Thissen, James B.; Gardner, Shea N.; McLoughlin, Kevin S.; Glausser, Margaret K.; Jaing, Crystal J.

    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 technology 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. PMID:24778651

  15. Screening of viral pathogens from pediatric ileal tissue samples after vaccination.

    PubMed

    Hewitson, Laura; Thissen, James B; Gardner, Shea N; McLoughlin, Kevin S; Glausser, Margaret K; Jaing, Crystal J

    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 technology 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. PMID:24778651

  16. Detection of an ileal cavernous hemangioma by technetium-99m red blood cell imaging

    SciTech Connect

    Holloway, H.; Johnson, J.; Sandler, M.

    1988-01-01

    Patients with arteriovenous malformations of the bowel may have multiple symptoms secondary to chronic blood loss. A case of ileal cavernous hemangioma detected by Tc-99m labeled red blood cell imaging in the absence of active gastrointestinal bleeding is presented.

  17. Effect of Partial Ileal Bypass on the Gut Hormone Responses to Food in Man

    Microsoft Academic Search

    J. M. Allen; D. L. Sarson; T. E. Adrian; C. Wood; G. R. Thompson; S. R. Bloom

    1983-01-01

    The integrated response of the regulatory peptides of the gastrointestinal tract to a test meal was studied in six hypercholesterolaemic patients who had undergone partial ileal bypass (PIB) and compared with responses in ten age- and sex-matched controls. Plasma motilin was found to rise significantly whereas plasma pancreatic polypeptide release was impaired after PIB. Plasma cholecystokinin rose promptly in both

  18. Management of fistula of ileal conduit in open abdomen by intra-condoit negative pressure system

    PubMed Central

    Yeti?ir, Fahri; Salman, A. Ebru; Aygar, Muhittin; Yaylak, Faik; Aksoy, Mustafa; Yalçin, Abdussamet

    2014-01-01

    INTRODUCTION We aimed to present the management of a patient with fistula of ileal conduit in open abdomen by intra-condoid negative pressure in conjunction with VAC Therapy and dynamic wound closure system (ABRA). PRESENTATION OF CASE 65-Year old man with bladder cancer underwent radical cystectomy and ileal conduit operation. Fistula from uretero-ileostomy anastomosis and ileus occurred. The APACHE II score was 23, Mannheim peritoneal index score was 38 and Björck score was 3. The patient was referred to our clinic with ileus, open abdomen and fistula of ileal conduit. Patient was treated with intra-conduid negative pressure, abdominal VAC therapy and ABRA. DISCUSSION Management of urine fistula like EAF in the OA may be extremely challenging. Especially three different treatment modalities of EAF are established in recent literature. They are isolation of the enteric effluent from OA, sealing of EAF with fibrin glue or skin flep and resection of intestine including EAF and re-anastomosis. None of these systems were convenient to our case, since urinary fistula was deeply situated in this patient with generalized peritonitis and ileus. CONCLUSION Application of intra-conduid negative pressure in conjunction with VAC therapy and ABRA is life saving strategies to manage open abdomen with fistula of ileal conduit. PMID:24858984

  19. Glutathione-Binding Site of a Bombyx mori Theta-Class Glutathione Transferase

    PubMed Central

    Hossain, M. D. Tofazzal; Yamada, Naotaka; Yamamoto, Kohji

    2014-01-01

    The glutathione transferase (GST) superfamily plays key roles in the detoxification of various xenobiotics. Here, we report the isolation and characterization of a silkworm protein belonging to a previously reported theta-class GST family. The enzyme (bmGSTT) catalyzes the reaction of glutathione with 1-chloro-2,4-dinitrobenzene, 1,2-epoxy-3-(4-nitrophenoxy)-propane, and 4-nitrophenethyl bromide. Mutagenesis of highly conserved residues in the catalytic site revealed that Glu66 and Ser67 are important for enzymatic function. These results provide insights into the catalysis of glutathione conjugation in silkworm by bmGSTT and into the metabolism of exogenous chemical agents. PMID:24848539

  20. Adaptive immune responses at mucosal surfaces of teleost fish.

    PubMed

    Rombout, Jan H W M; Yang, Guiwen; Kiron, Viswanath

    2014-10-01

    This review describes the extant knowledge on the teleostean mucosal adaptive immune mechanisms, which is relevant for the development of oral or mucosal vaccines. In the last decade, a number of studies have shed light on the presence of new key components of mucosal immunity: a distinct immunoglobulin class (IgT or IgZ) and the polymeric Ig receptor (pIgR). In addition, intestinal T cells and their putative functions, antigen uptake mechanisms at mucosal surfaces and new mucosal vaccination strategies have been reported. New information on pIgR of Atlantic cod and common carp and comparison of natural and specific cell-mediated cytotoxicity in the gut of common carp and European seabass, is also included in this review. Based on the known facts about intestinal immunology and mucosal vaccination, suggestions are made for the advancement of fish vaccines. PMID:25150451

  1. 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

  2. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...determine the activity of the enzyme glutathione reductase in serum, plasma, or erythrocytes by such techniques as fluorescence and photometry. The results of this assay are used in the diagnosis of liver disease, glutathione reductase deficiency, or...

  3. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...reductase assay. (a) Identification. A glutathione reductase assay is a device used to determine the activity of the enzyme glutathione reductase in serum, plasma, or erythrocytes by such techniques as fluorescence and photometry. The...

  4. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...reductase assay. (a) Identification. A glutathione reductase assay is a device used to determine the activity of the enzyme glutathione reductase in serum, plasma, or erythrocytes by such techniques as fluorescence and photometry. The...

  5. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY...glutathione reductase assay is a device used to determine the activity of the enzyme glutathione reductase in serum, plasma, or...

  6. Effect of colonic distention on ileal motor activity with evidence of coloileal reflex.

    PubMed

    Shafik, Ahmed; Shafik, Ali A; Ahmed, Ismail

    2003-01-01

    Chyme delivery from the ileum to the colon is controlled by various neurologic and hormonal factors, many of which remain to be identified. In this report we investigated the effect of colonic distention on ileal motility with the aim of identifying the mechanism of chyme delivery from the ileum to the colon. The right colon of 16 healthy volunteers (12 men and 4 women; mean age 36+/-9 years standard deviation) was distended by a balloon that was filled with saline solution in increments of 20 ml. The pressure response of the terminal ileum to the colonic distention was recorded by a saline-perfused tube. The test was repeated in nine subjects after the colonic segment around the balloon was anesthetized by xylocaine injection into the colonic wall. Twenty and 40 ml colonic distention produced no significant ileal pressure response. Colonic distention with 60 ml produced an increase in colonic pressure (P<0.05), as measured by intraballoon pressure, and a decrease in ileal pressure (P<0.05); a similar response was achieved with 80 ml distention. At 100 ml colonic distention, the balloon was dispelled to the transverse colon. Distention up to 100 ml of the anesthetized colonic segment produced no significant colonic or ileal pressure response. The flow of chyme from the small to the large gut appears to be controlled by a reflex mechanism that we call the "coloileal reflex." Whenever the right colon is distended with a substantial volume of chyme that increases the intraluminal pressure, it is suggested that ileal relaxation occurs, which delays the emptying of chyme from the ileum. PMID:12850685

  7. Characterization of B-cell phenotypic changes during ileal and jejunal Peyer's patch development in sheep.

    PubMed Central

    Griebel, P J; Kennedy, L; Graham, T; Davis, W C; Reynolds, J D

    1992-01-01

    Changes in B-cell phenotype during development of ileal and jejunal Peyer's patches (PP) of sheep were investigated using flow cytometry and immunoperoxidase-stained cryosections. On Day 104 of gestation (term at 150 days) B-cell clusters were identified in the lamina propria of the ileum. These clusters were composed of cells that expressed surface IgM (sIgM), lambda or kappa light chain, and BAQ44A, a B-cell differentiation molecule. No cells in the clusters stained for terminal deoxynucleotide transferase. On Day 132 gestation, a change was evident in the phenotype of ileal PP B cells. Most B cells expressed a reduced level of sIgM and 20% were BAQ44A-. The B cells in the dome region were BAQ44A+ but few BAQ44A+ cells were present in the follicles. At 6-8 weeks of age BAQ44A+ cells were restricted to the dome region of the ileal PP; flow cytometric analysis confirmed that 25% of B cells isolated from the dome/follicle complex were BAQ44A+. Thus, the primordial PP was populated with B cells that were phenotypically similar to circulating B cells (sIgMhigh, BAQ44A+). After 132 days gestation, the predominant B-cell phenotype in the ileal PP changed to sIgMlow and BAQ44A-. This phenotypic change could be the result of either early immigrant B-cell differentiation or subsequent colonization by sIgMlow BAQ44A- B cells. The phenotypic changes of ileal PP follicular B cells were not complete until after birth and different phenotypic changes were observed in follicles of the jejunal PP of young lambs. Images Figure 1 Figure 2 Figure 4 PMID:1493930

  8. Ileal and total tract nutrient digestibility in blue foxes (Alopex lagopus) fed extruded diets containing different protein sources.

    PubMed

    Vhile, Stine G; Skrede, Anders; Ahlstrøm, Oystein; Szymeczko, Roman; Hove, Knut

    2005-02-01

    This study compared apparent ileal and total tract digestibility of macronutrients and amino acids in blue foxes (Alopex lagopus) fed dry extruded diets. The control diet contained fish meal as the main protein source, while in the other diets 50% of the fish meal protein was replaced by not de-hulled solvent-extracted soybean meal, meat meal or bacterial protein meal. Ileal digestibility was obtained with animals modified with ileorectal anastomosis (IRA method). There were no significant differences in the average digestibility of CP, Lys, Trp, Val, Ala or Glu between IRA modified and intact animals. Average ileal digestibilities of His, Thr, Asp, Cys, Gly, Hyp, Pro, Ser, starch and total carbohydrates (CHO) were significantly lower compared with total tract values. Average ileal digestibility of Arg, Ile, Leu, Met, Phe, Tyr and crude fat was significantly higher than total tract digestibility. Digestibility measured in IRA modified animals showed less variability compared with values from intact animals. There were significant differences among diets in ileal as well as total tract digestibility of orude protein, most amino acids, starch and CHO, and in ileal digestibility of crude fat. Ileal crude protein digestibility of the diets ranged from 81.0-86.4% and total tract digestibility from 82.5-86.4%. Ileal amino acid digestibilities ranged from 70.1 (Asp) to 93.3% (Arg) and total tract values ranged from 72.8 (Cys) to 92.2% (Arg). Both ileal and total tract digestibilities of crude protein and most amino acids were significantly lower for diets containing meat meal or bacterial protein meal compared with the control fish meal-based diet and the diet with soybean meal. Although ileal digestibility may be more accurate than total tract digestibility in estimating the protein and amino acid supply in blue foxes, total tract digestibility may be acceptable because of numerically small differences between ileal and total tract digestibilities for protein and most amino acids. It was further concluded that ileal digestibilities of starch and CHO in the blue fox are lower than corresponding total tract digestibilities. PMID:15889653

  9. Minimal invasive treatment of benign anastomotic uretero-ileal stricture in Hautmann neobladder with thermoexpandable ureteral metal stent

    PubMed Central

    Efthimiou, Ioannis P.; Porfyris, Orestis T.; Kalomoiris, Paraskevas I.

    2015-01-01

    Technical challenges and increased morbidity of open reconstruction for uretero-ileal strictures have led to a search for minimal invasive treatments as an alternative solution. The insertion of a thermo-expandable ureteral Memokath 051® metal stent across benign uretero-ileal anastomotic stricture in orthotopic neobladder has not been described in the English literature. Herein, we describe a case of a woman with a Hautmann neobladder and a 3.5 cm benign stricture of the right uretero-ileal anastomosis that was treated with insertion of a thermo-expandable ureteral Memokath 051® metal stent. PMID:25878417

  10. Ileal substitute of ureter with reflux-plasty by terminal intussusception of bowel: animal experiments and clinical experience.

    PubMed

    Tscholl, R; Tettamanti, F; Zingg, E

    1977-04-01

    The conflicting results reported after substitution of the ureter by isolated bowel segments suggest that the procedure is still hazardous. This induced us to check experimentally the performance of the ileal ureter with antireflux-plasty before using it clinically. The antireflux mechanism is constructed by intussuscepting the terminal 8 cm. of an isolated ileal segment into each other thus forming a nipple. After vesicoileostomy the nipple protrudes into the urinary bladder. In the pig vesicoileorenal reflux was prevented, and anterograde urinary flow from the kidney through the ileal ureter into the bladder was unobstructed. Finally, the case of a patient is recorded who was submitted to the same procedure successfully. PMID:857371

  11. Consequences of erythrocytic glutathione reductase deficiency.

    PubMed

    Frischer, H; Ahmad, T

    1987-05-01

    We have used 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) as a selective and irreversible inhibitor of oxidized glutathione reductase (GSSG-R) to determine how human erythrocytes with various degrees of GSSG-R deficiency recover their reduced glutathione (GSH) after exposure to acetylphenylhydrazine or diamide. Pentose phosphate dehydrogenases and glutathione synthesis were not inhibited, de novo glutathione synthesis was negligible within the experimental time frame, and the reappearance of GSH was strictly under the control of GSSG-R. Results obtained with acetylphenylhydrazine or diamide were concordant. In red cells stressed by these reagents, GSSG-R deficiency began to impair the regeneration of GSH only after greater than 80% of the normal enzyme activity had been abolished. Thereafter GSH recovery deteriorated as drug-induced GSSG-R depression increased. Only erythrocytes that had been rendered almost totally GSSG-R deficient, that is, had lost greater than 90% of baseline activity, became functionally equivalent to GdA- glucose-6-phosphate dehydrogenase-deficient cells. The reserve capacity of GSSG-R in human erythrocytes is extremely large. Of all types of isolated GSSG-R "deficiencies" reported so far, only two can be considered pathogenically significant: the homozygous genetic defect found in a single family, and much more commonly, the acute pharmacologic phenocopy induced by BCNU. PMID:3572207

  12. Linked thioredoxin-glutathione systems in platyhelminths

    E-print Network

    Maizels, Rick

    Linked thioredoxin-glutathione systems in platyhelminths Gustavo Salinas1 , Murray E. Selkirk2 have recently been characterized in platyhelminth parasites, and the emerging biochemical scenario in platyhelminths [4­6]. Selenocysteine (Sec, see Box 1)-containing TGR appears to be the major oxido

  13. 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

  14. Microbiota and their role in the pathogenesis of oral mucositis.

    PubMed

    Vanhoecke, B; De Ryck, T; Stringer, A; Van de Wiele, T; Keefe, D

    2015-01-01

    Oral mucositis in patients undergoing cancer therapy is a significant problem. Its prevalence ranges between 20 and 100%, depending on treatment type and protocols and patient-based variables. Mucositis is self-limiting when uncomplicated by infection. Unfortunately, the incidence of developing a local or systemic infection during the course of the treatment is very high. At this stage, it is unclear which role oral microbiota play in the onset, duration, and severity of oral mucositis. Nevertheless, there is growing interest in this underexplored topic, and new studies are being undertaken to unravel their impact on the pathogenesis of mucositis. PMID:24456144

  15. Vaccination of goats with a glutathione peroxidase DNA vaccine induced partial protection against Haemonchus contortus infection.

    PubMed

    Sun, Wei; Song, Xiaokai; Yan, Ruofeng; Xu, Lixin; Li, Xiangrui

    2011-12-15

    Due to their critical functions in worm physiology, glutathione peroxidases in Haemonchus contortus are potential candidates for vaccine to control haemonchosis. However, information on the protection potential of these molecules is lacking. In this study, recombinant HC29 antigen was tested for protection against experimental H. contortus infections in goats. Fifteen animals were allocated into three trial groups. The animals of HC29 group was vaccinated with a recombinant HC29 DNA vaccine twice at day 0 and day 14, and then challenged with 5000 infective H. contortus L3 (third larval stage) on the 28th day. An unvaccinated positive control group was challenged with L3 at the same time. An unvaccinated negative control group was not challenged with L3. The results indicated HC29 DNA vaccine was transcribed at local injection sites and expressed in vivo post immunizations, respectively. Following L3 challenge, the mean eggs per gram feces and worm burdens of HC29 group were reduced by 36.1% and 35.6% respectively compared to the positive control group. After immunization with the DNA vaccine, significantly high levels of serum IgG, serum IgA, mucosal IgA and CD4(+) T lymphocytes were detected. These results suggest that recombinant H. contortus HC29 glutathione peroxidase DNA vaccine induced a partial immune response and has protective potentials against caprine haemonchosis. PMID:21680097

  16. Original article Assessment of blood glutathione peroxidase activity

    E-print Network

    Boyer, Edmond

    Original article Assessment of blood glutathione peroxidase activity in the dromedary camel Juan ­ Blood glutathione peroxidase (GSH-Px) levels in 709 normal dromedary camels (442 females and 267 males. dromedary / camel / nutritional myodegeneration / glutathione peroxidase / selenium Résumé ­ Détermination

  17. Oral mucosal immunization using glucomannosylated bilosomes.

    PubMed

    Jain, Sanyog; Indulkar, Anura; Harde, Harshad; Agrawal, Ashish K

    2014-06-01

    The present study embarks on the feasibility of GM-bilosomes as a rationally designed vehicle for oral mucosal immunization. Bilosomes containing BSA as a model antigen were found to have vesicle size of 157 +/- 3 nm, PDI of 0.287 +/- 0.045, zeta potential of -21.8 +/- 2.01 mV and entrapment efficiency of 71.3 +/- 4.3%. Bilosomal formulations were freeze dried and entrapped BSA in freeze dried formulations was found to retain its structural and conformational stability as evident by SDS-PAGE and CD analysis. The GM-bilosomes were also found stable in different simulated biological fluids and bile salt solutions of different concentrations. In-vitro drug release revealed that GM-bilosomes were able to sustain drug release up to 24 h. In-vitro cell uptake in RAW 264.7 macrophage cells demonstrated significantly higher uptake of GM-bilosomes in comparison with bilosomes and free antigen. Intestinal uptake studies on excised rat intestinal sections further demonstrated higher uptake of vesicular systems throughout the intestinal region in comparison with free antigen. Significantly higher (p < 0.05) systemic immune response (serum IgG level) was observed in case of GM-bilosomes in comparison with bilosomes and alum adsorbed BSA (BSA-AL) following oral administration. The immune response observed in case of GM-bilosomes was comparable to BSA-AL administered through im route without any significant difference (p > 0.05). More importantly, GM-bilosomes were found capable of inducing mucosal immune response as well as cell mediated immune response which was not induced by im BSA-AL. In conclusion, GM-bilosomes could be considered as promising carrier and adjuvant system for oral mucosal immunization and productively exploited for oral delivery of other candidate antigens. PMID:24749389

  18. Gastric Mucosal Protection by Aegle Marmelos Against Gastric Mucosal Damage: Role of Enterochromaffin Cell and Serotonin

    PubMed Central

    Singh, Purnima; Dutta, Shubha R.; Guha, Debjani

    2015-01-01

    Background/Aims: Serotonin (5-hydroxytryptamine; 5-HT) released from enterochromaffin (EC) cells in gastric mucosa inhibits gastric acidity by increasing the gastric mucus secretion. In the present study, we evaluated the effect of aqueous extract of Aegle marmelos (AM) ripe fruit pulp (250 mg/kg body weight) on mean ulcer index (MUI), EC cells, 5-HT content, and adherent mucosal thickness of ulcerated gastric tissue in adult albino rats. Material and Methods: Ulceration was induced by using aspirin (500 mg/kg, p.o.), cerebellar nodular lesion and applying cold-restraint stress. Results: In all cases increased MUI in gastric tissue along with decreased EC cell count was observed with concomitant decrease of 5-HT content and adherent mucosal thickness (P < 0.05). Pretreatment with AM for 14 days decreased MUI, increased EC cell count, and 5-HT content as well as adherent mucosal thickness in all ulcerated group (P < 0.05). Conclusion: AM produces gastric mucosal protection mediated by increased EC cell count and 5-HT levels. PMID:25672237

  19. [A case of mucosal Schwann cell hamartoma].

    PubMed

    Sagami, Shintaro; Fukumoto, Akira; Amano, Mio; Yamao, Kentaro; Hashimoto, Yoshimasa; Iiboshi, Tomohiro; Onogawa, Seiji; Hirano, Naomichi; Hanada, Keiji; Amano, Hajime; Hino, Fumiaki; Yonehara, Shuji

    2012-10-01

    A 40-year-old man was referred to our hospital because of a positive fecal occult blood test. Colonoscopy revealed many small whitish nodules in the mucosa of the sigmoid colon. Specimens endoscopically resected from the lesions revealed spindle cell proliferation in the lamina propria. Immunohistochemical study revealed strong and diffuse positivity for S-100 protein. Results of staining for neurofilament protein and epithelial membrane antigen were negative. The neurogenic tumors were diagnosed as mucosal Schwann cell hamartoma. No clinical features of multiple endocrine neoplasia type 2B or neurofibromatosis type 1 were found in the present case. PMID:23047636

  20. Glutathione, Glutathione S-Transferase and Reactive Oxygen Species of Human Scalp Sebaceous Glands in Male Pattern Baldness

    Microsoft Academic Search

    Montserrat Giralt; Isabel Cervello; María Rosa Nogues; Antonia María Puerto; Francesca Ortin; Núria Argany; Jordi Mallol

    1996-01-01

    We investigated the contribution of reactive oxygen species to the development of sebaceous gland hyperplasia and the characteristics of the glutathione S-transferase\\/glutathione system in male pattern baldness. Glutathione S-transferase, glutathione, and thiobarbituric acid-reactive substances were determined in sebaceous gland-enriched scalp skin of men affected by male pattern baldness and were subjected to hair autotransplantation. In comparison with the hairy occipital-donor

  1. Mucosal Imprinting of Vaccine-Induced CD8+ T Cells Is Crucial to Inhibit the Growth of Mucosal Tumors

    PubMed Central

    Sandoval, Federico; Bureau, Michel-Francis; Freyburger, Ludovic; Clement, Olivier; Marcheteau, Elie; Gey, Alain; Fraisse, Guillaume; Bouguin, Cécilia; Merillon, Nathalie; Dransart, Estelle; Tran, Thi; Quintin-Colonna, Françoise; Autret, Gwennhael; Thiebaud, Marine; Suleman, Muhammad; Riffault, Sabine; Wu, Tzyy-Choou; Launay, Odile; Danel, Claire; Taieb, Julien; Richardson, Jennifer; Zitvogel, Laurence; Fridman, Wolf H.; Johannes, Ludger; Tartour, Eric

    2014-01-01

    Although many human cancers are located in mucosal sites, most cancer vaccines are tested against subcutaneous tumors in preclinical models. We therefore wondered whether mucosa-specific homing instructions to the immune system might influence mucosal tumor outgrowth. We showed that the growth of orthotopic head and neck or lung cancers was inhibited when a cancer vaccine was delivered by the intranasal mucosal route but not the intramuscular route. This antitumor effect was dependent on CD8+ T cells. Indeed, only intranasal vaccination elicited mucosal-specific CD8+ T cells expressing the mucosal integrin CD49a. Blockade of CD49a decreased intratumoral CD8+ T cell infiltration and the efficacy of cancer vaccine on mucosal tumor. We then showed that after intranasal vaccination, dendritic cells from lung parenchyma, but not those from spleen, induced the expression of CD49a on cocultured specific CD8+ T cells. Tumor-infiltrating lymphocytes from human mucosal lung cancer also expressed CD49a, which supports the relevance and possible extrapolation of these results in humans. We thus identified a link between the route of vaccination and the induction of a mucosal homing program on induced CD8+ T cells that controlled their trafficking. Immunization route directly affected the efficacy of the cancer vaccine to control mucosal tumors. PMID:23408053

  2. Mucosal imprinting of vaccine-induced CD8? T cells is crucial to inhibit the growth of mucosal tumors.

    PubMed

    Sandoval, Federico; Terme, Magali; Nizard, Mevyn; Badoual, Cécile; Bureau, Michel-Francis; Freyburger, Ludovic; Clement, Olivier; Marcheteau, Elie; Gey, Alain; Fraisse, Guillaume; Bouguin, Cécilia; Merillon, Nathalie; Dransart, Estelle; Tran, Thi; Quintin-Colonna, Françoise; Autret, Gwennhael; Thiebaud, Marine; Suleman, Muhammad; Suleman, Muhammed; Riffault, Sabine; Wu, Tzyy-Choou; Launay, Odile; Danel, Claire; Taieb, Julien; Richardson, Jennifer; Zitvogel, Laurence; Fridman, Wolf H; Johannes, Ludger; Tartour, Eric

    2013-02-13

    Although many human cancers are located in mucosal sites, most cancer vaccines are tested against subcutaneous tumors in preclinical models. We therefore wondered whether mucosa-specific homing instructions to the immune system might influence mucosal tumor outgrowth. We showed that the growth of orthotopic head and neck or lung cancers was inhibited when a cancer vaccine was delivered by the intranasal mucosal route but not the intramuscular route. This antitumor effect was dependent on CD8? T cells. Indeed, only intranasal vaccination elicited mucosal-specific CD8? T cells expressing the mucosal integrin CD49a. Blockade of CD49a decreased intratumoral CD8? T cell infiltration and the efficacy of cancer vaccine on mucosal tumor. We then showed that after intranasal vaccination, dendritic cells from lung parenchyma, but not those from spleen, induced the expression of CD49a on cocultured specific CD8? T cells. Tumor-infiltrating lymphocytes from human mucosal lung cancer also expressed CD49a, which supports the relevance and possible extrapolation of these results in humans. We thus identified a link between the route of vaccination and the induction of a mucosal homing program on induced CD8? T cells that controlled their trafficking. Immunization route directly affected the efficacy of the cancer vaccine to control mucosal tumors. PMID:23408053

  3. Intracellular adaptations of glutathione content in Cucurbita pepo L. induced by treatment with reduced glutathione and buthionine sulfoximine.

    PubMed

    Zechmann, B; Müller, M; Zellnig, G

    2006-05-01

    The intracellular effects of GSH (reduced glutathione) and BSO (buthionine sulfoximine) treatment on glutathione content were investigated with immunogold labeling in individual cellular compartments of Cucurbita pepo L. seedlings. Generally, GSH treatment led to increased levels of glutathione in roots and leaves (up to 3.5-fold in nuclei), whereas BSO treatment significantly decreased glutathione content in all organs. Transmission electron microscopy revealed that glutathione levels in mitochondria, which showed the highest glutathione labeling density of all compartments, remained generally unaffected by both treatments. Since glutathione within mitochondria is involved in the regulation of cell death, these results indicate that high and stable levels of glutathione in mitochondria play an important role in cell survival strategies. BSO treatment significantly decreased glutathione levels (1) in roots by about 78% in plastids and 60.8% in the cytosol and (2) in cotyledons by about 55% in the cytosol and 38.6% in plastids. After a short recovery period, glutathione levels were significantly increased in plastids and the cytosol of root tip cells (up to 3.7-fold) and back to control values in cotyledons. These results indicate that plastids, either alone or together with the cytosol, are the main center of glutathione synthesis in leaves as well as in roots. After GSH treatment for 24 h, severe ultrastructural damage related to increased levels of glutathione was found in roots, in all organelles except mitochondria. Possible negative effects of GSH treatment leading to the observed ultrastructural damage are discussed. PMID:16520878

  4. Generation of Effector Memory T Cell-Based Mucosal and Systemic Immunity with Pulmonary Nanoparticle Vaccination

    E-print Network

    Li, Adrienne V.

    Many pathogens infiltrate the body and initiate infection via mucosal surfaces. Hence, eliciting cellular immune responses at mucosal portals of entry is of great interest for vaccine development against mucosal pathogens. ...

  5. 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 contents may be suggestive, at least in part, of overestimation of P digestibility under the calcium-deficient conditions used in the regression method. PMID:25367524

  6. Direct measurement of first-pass ileal clearance of a bile acid in humans.

    PubMed

    Galatola, G; Jazrawi, R P; Bridges, C; Joseph, A E; Northfield, T C

    1991-04-01

    The purpose of this study was to develop and validate a method of directly measuring ileal bile acid absorption efficiency during a single enterohepatic cycle (first-pass ileal clearance). This has become feasible for the first time because of the availability of the synthetic gamma-labeled bile acid 75Selena-homocholic acid-taurine (75SeHCAT). Together with the corresponding natural bile acid cholic acid-taurine (labeled with 14C), SeHCAT was infused distal to an occluding balloon situated beyond the ampulla of Vater in six healthy subjects. Completion of a single enterohepatic cycle was assessed by obtaining a plateau for 75SeHCAT activity proximal to the occluding balloon, which prevented further cycles. Unabsorbed 75SeHCAT was collected after total gut washout, which was administered distal to the occluding balloon. 75SeHCAT activity in the rectal effluent measured by gamma counter was compared with that of absorbed 75SeHCAT level measured by gamma camera and was used to calculate first-pass ileal clearance. This was very efficient (mean value, 96%) and showed very little variation in the six subjects studied (range, 95%-97%). A parallel time-activity course in hepatic bile for 14C and 75Se during a single enterohepatic cycle, together with a ratio of unity for 14C/75Se in samples obtained at different time intervals, suggests that 75SeHCAT is handled by the ileum like the natural bile acid cholic acid-taurine. Extrapolation of 75SeHCAT first-pass ileal clearance to that of the natural bile acid therefore seems justifiable. In a subsidiary experiment, ileal absorption efficiency per day for 75SeHCAT was also measured by scanning the gallbladder area on 5 successive days after the measurement of first-pass ileal clearance. In contrast with absorption efficiency per cycle, absorption efficiency per day varied widely (49%-86%), implying a possible wide variation in recycling frequency per day. PMID:2001808

  7. Barriers to mucosal transmission of immunodeficiency viruses

    PubMed Central

    Estes, Jacob D.

    2011-01-01

    Lentiviruses such as HIV have a daunting challenge in gaining access to a new host predominantly through the penile, rectal, or vaginal/cervical mucosal tissue after sexual exposure. Multiple mechanisms have evolved to help prevent such infections, including anatomical barriers, innate inhibitors, and adaptive immune responses. For lentiviruses, it appears that in naive or even conventionally vaccinated hosts, typical adaptive immune responses are generally too little and too late to prevent infection. Nevertheless, a combination of anatomical barriers and innate immune responses may limit transmission, especially in patients without predisposing conditions such as mucosal lesions or preexisting sexually transmitted infections. Furthermore, when infection does occur, most often the primary viremia of the acute infection can be traced back genetically to a single founder virus. Unfortunately, even a single virion can establish an infection that will ultimately lead to the demise of the host. This review seeks to describe the biology of and barriers to establishment of systemic, disseminated productive infection with HIV after sexual exposure and to discuss the possible mechanisms leading to infection by a single viral variant. Understanding the initial events of infection, before systemic spread, could provide insights into strategies for reducing acquisition or ameliorating clinical outcome. PMID:21555745

  8. 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. PMID:25459886

  9. Dietary fibre affects intestinal mucosal barrier function and regulates intestinal bacteria in weaning piglets.

    PubMed

    Chen, Hong; Mao, Xiangbing; He, Jun; Yu, Bing; Huang, Zhiqing; Yu, Jie; Zheng, Ping; Chen, Daiwen

    2013-11-01

    The objective of the present study was to evaluate the effects of fibre source on intestinal mucosal barrier function in weaning piglets. A total of 125 piglets were randomly allotted on the basis of their body weight and litters to one of five experimental diets, i.e. a control diet without fibre source (CT), and diets in which expanded maize was replaced by 10% maize fibre (MF), 10% soyabean fibre (SF), 10% wheat bran fibre (WBF) or 10% pea fibre (PF). The diets and water were fed ad libitum for 30 d. Piglets on the WBF and PF diets had lower diarrhoea incidence compared with the MF- and SF-fed animals. A higher ratio of villous height:crypt depth in the ileum of WBF-fed piglets and higher colonic goblet cells in WBF- and PF-fed piglets were observed compared with CT-, MF- and SF-fed piglets. In the intestinal digesta, feeding WBF and PF resulted in increased Lactobacillus counts in the ileum and Bifidobacterium counts in the colon. Lower Escherichia coli counts occurred in the ileum and colon of WBF-fed piglets than in SF-fed piglets. Tight junction protein (zonula occludens 1; ZO-1) and Toll-like receptor 2 (TLR2) gene mRNA levels were up-regulated in the ileum and colon of pigs fed WBF; however, feeding MF and SF raised IL-1? and TNF-? mRNA levels. Furthermore, higher diamine oxidase activities, transforming growth factor-?, trefoil factor family and MHC-II concentration occurred when feeding WBF and PF. In conclusion, the various fibre sources had different effects on the ileal and colonic barrier function. Clearly, WBF and PF improved the intestinal barrier function, probably mediated by changes in microbiota composition and concomitant changes in TLR2 gene expression. PMID:23656640

  10. Circulatory Antigen Processing by Mucosal Dendritic Cells Controls CD8+

    E-print Network

    Immunity Article Circulatory Antigen Processing by Mucosal Dendritic Cells Controls CD8+ T Cell and are distinct from CD103+ DCs derived from a common DC progenitor in an Flt3L-dependent pathway (Varol et al or how this process controls mucosal immune responses remains unknown. Here we demonstrate that dendritic

  11. The sonographic appearance of intestinal mucosal fibrosis in cats.

    PubMed

    Penninck, Dominique G; Webster, Cynthia R L; Keating, John H

    2010-01-01

    The medical records of 11 cats with full-thickness intestinal biopsies and histopathologic confirmation of segmental mucosal fibrosis were reviewed. All cats received an abdominal ultrasonographic evaluation. The sonographic feature of a small intestinal mucosal hyperechoic band paralleling the submucosa was present in all cats. Other intestinal sonographic findings included wall thickening, and altered wall layering (increased mucosal echogenicity, thickened submucosa, and/or muscularis layer). None of the cats had complete loss of wall stratification. All cats had clinical signs related to the gastrointestinal (GI) tract at the time of presentation. Three of the 11 cats had palpably thickened small intestinal loops, 3/11 abdominal pain, and 2/11 abdominal fluid. Histopathologically, mucosal fibrosis was associated with inflammatory cell infiltrates in all cats. In those cats with histopathologic evidence of mural fibrosis, all cats had a visible hyperechoic band through several intestinal segments. We speculate that the hyperechoic mucosal band represents the zone of mucosal fibrosis. Independently and prospectively, we reviewed the clinical presentation of 35 cats having this visible hyperechoic mucosal band on ultrasound. Twenty-four of these 35 cats had clinical signs related to the digestive system at the time of record. Our study suggests that the hyperechoic mucosal band represents fibrosis, and in presence of concurrent GI signs, further diagnostic tests may be warranted. PMID:20806880

  12. 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. PMID:19566248

  13. THE MUCOSAL DISACCHARIDASES IN THE SMALL INTESTINE OF THE CALF

    E-print Network

    Paris-Sud XI, Université de

    THE MUCOSAL DISACCHARIDASES IN THE SMALL INTESTINE OF THE CALF F. TOOFANIAN F. W. G. HILL D. E intestinal mucosal enzymes are respon- sible for this hydrolysis. In the young pre-ruminant and non compartments of the stomach. Thus, the intestinal disaccharidases have a much smaller role. For this reason

  14. Investigations of TB vaccine-induced mucosal protection in mice

    PubMed Central

    Blazevic, Azra; Eickhoff, Christopher S.; Stanley, Jaime; Buller, Mark R.; Schriewer, Jill; Kettelson, Eric M.; Hoft, Daniel F.

    2013-01-01

    A better understanding of mucosal immunity is required to develop more protective vaccines against Mycobacterium tuberculosis. We developed a murine aerosol challenge model to investigate responses capable of protecting against mucosal infection. Mice received vaccinations intranasally with CpG-adjuvanted antigen 85B (Ag85B/CpG) and/or Bacillus Calmette-Guerin (BCG). Protection against aerosol challenge with a recombinant GFP- expressing BCG was assessed. Mucosal prime/boost vaccinations with Ag85B/CpG and BCG were protective, but did not prevent lung infection indicating more efficacious mucosal vaccines are needed. Our novel finding that protection correlated with increased airway dendritic cells early post-challenge could help guide the development of enhanced mucosal vaccines. PMID:24120457

  15. Potential role for mucosally active vaccines against pneumococcal pneumonia

    PubMed Central

    Jambo, Kondwani C.; Sepako, Enoch; Heyderman, Robert S.; Gordon, Stephen B.

    2010-01-01

    Pneumococcal pneumonia is a life-threatening disease with high mortality and morbidity among children under 5 years of age, the elderly and immunocompromised individuals worldwide. Protection against pneumococcal pneumonia relies on successful regulation of colonisation in the nasopharynx and a brisk alveolar macrophage-mediated immune response in the lung. Therefore, enhancing pulmonary mucosal immunity (which includes a combination of innate, humoral and cell-mediated immunity) through mucosal vaccination might be the key to prevention of pneumococcal infection. Current challenges include a lack of information in humans on mucosal immunity against pneumococci and a lack of suitable adjuvants for new vaccines. Data from mouse models, however, suggest that mucosally active vaccines will enhance mucosal and systemic immunity for protection against pneumococcal infection. PMID:20031415

  16. Prevention and treatment of oral mucositis in patients receiving chemotherapy

    PubMed Central

    Sarrión-Pérez, Maria G.

    2014-01-01

    Oral mucositis is one of the most common side effects of cancer treatment (chemotherapy and/or radiotherapy). It is an inflammatory process that affects the mucosa of the oral cavity, giving rise to erythematous areas in combination with ulcers that can reach a large size. The true importance of oral mucositis is the complications it causes – fundamentally intense pain associated to the oral ulcers, and the risk of overinfection. This in turn may require reduction or even suspension of the antineoplastic treatment, with the risk of seriously worsening the patient prognosis. This points to the importance of establishing therapeutic tools of use in the prevention and/or treatment of mucositis. The present study offers a literature review of all the articles published over the last 10 years referred to the prevention and/or treatment of oral mucositis associated to chemotherapy. Key words:Oral mucositis, management, prevention, treatment, chemotherapy. PMID:24596640

  17. Effect of glutathione addition in sparkling wine.

    PubMed

    Webber, Vanessa; Dutra, Sandra Valduga; Spinelli, Fernanda Rodrigues; Marcon, Ângela Rossi; Carnieli, Gilberto João; Vanderlinde, Regina

    2014-09-15

    This study aims to evaluate the effect of the addition of glutathione (GSH) on secondary aromas and on the phenolic compounds of sparkling wine elaborated by traditional method. It was added 10 and 20 mg L(-1) of GSH to must and to base wine. The determination of aroma compounds was performed by gas chromatography. Phenolic compounds and glutathione content were analyzed by high performance liquid chromatography. Sparkling wines with addition of GSH to must showed lower levels of total phenolic compounds and hydroxycinnamic acids. Furthermore, the sparkling wine with addition of GSH to must showed higher levels of 2-phenylethanol, 3-methyl-1-butanol and diethyl succinate, and lower concentrations of ethyl decanoate, octanoic and decanoic acids. The GSH addition to the must show a greater influence on sparkling wine than to base wine, however GSH addition to base wine seems retain higher SO2 free levels. The concentration of GSH added showed no significant difference. PMID:24767072

  18. Role of Glutathione in Abiotic Stress Tolerance

    Microsoft Academic Search

    S. Srivalli; Renu Khanna-Chopra

    Reduced glutathione (GSH) is the most abundant source of nonprotein thiols in plant cells. It has multiple functions in plants,\\u000a including cell differentiation, cell death and senescence, pathogen resistance, enzymatic regulation, as an antioxidant, in\\u000a formation of phytochelatins, detoxification of xenobiotics, and also acts as a storage and transport form of reduced sulfur.\\u000a Along with its oxidized form (GSSG), it

  19. Hypoxia increases plasma glutathione disulfide in rats

    Microsoft Academic Search

    Shih-Wen Chang; Thomas J. Stelzner; John V. Weil; Norbert F. Voelkel

    1989-01-01

    We tested the hypothesis that hypoxia causes cellular oxidative stress by measuring plasma concentrations of glutathione disulfide\\u000a (GSSG) in rats exposed to acute and subacute hypoxia. In awake, unanesthetized, catheter-implanted rats, exposure to 8% O2 for 10 min caused pulmonary vasoconstriction and increased plasma GSSG. This increase in plasma GSSG was reversible upon\\u000a re-exposure to room air. In another group

  20. Quality of life of patients after temporary ileostomy for ileal perforation- a questionnaire based study.

    PubMed

    Saini, Pradeep; Gaba, Rahul; Faridi, M S; Agarwal, Nitin; Kaur, Navneet; Gupta, Arun

    2014-02-01

    In India and some neighboring countries, ileal perforation is a leading indication for an emergent laparotomy, and making a temporary ileostomy is probably the safest practice for these patients with peritonitis. This apparently disfiguring surgery changes body image, and significantly influences physical, mental, emotional, and social life of the stoma patients. Further stress is added by the stoma related complications. The quality of life (QoL) issues of patients with temporary ileostomy for ileal perforations have not been addressed; hence, there is a gap in our existing knowledge about the various factors affecting the quality of life of these patients. This study aimed at assessing the QoL in this particular group of patients with the help of an objective standardized proforma-based interview. Despite being limited by its small sample size, the study identifies important associations and provides a platform for further research to improve QoL of these patients. PMID:24799782

  1. Sacrocolpopexy with Polypropylene Tape as Valuable Surgical Modification during Cystectomy with Orthotopic Ileal Bladder: Functional Results

    PubMed Central

    ?yczkowski, Marcin; Kaletka, Zbigniew; Bryniarski, Piotr; Paradysz, Andrzej

    2015-01-01

    Introduction. Urinary diversion is very often associated with urinary retention and urinary incontinence. In this study, a surgical modification during cystectomy with orthotopic ileal neobladder is presented. Material and Methods. Female patients enrolled in the study (n-24) were subjected to sacrocolpopexy during the operation. Apart from oncological control, the follow-up consisted of 1-hour inlay test and questionnaires (UDI-6 and IIQ-7) in the 3rd, 6th, and 12th month after the operation. In the 12th month after the surgery, the urodynamic pressure-flow test was performed. Outcomes were compared with the control group (n-18) in which sacrocolpopexy was not implemented. Results. The study group was characterised by reduced urinary retention and improved continence. Conclusion. Sacrocolpopexy during cystectomy with orthotopic ileal bladder is a valuable surgical method which provides patients with a better quality of life. PMID:25789311

  2. Straight ileoanal anastomosis and ileal pouch-anal anastomosis in the surgical management of idiopathic ulcerative colitis and familial polyposis coli in children: follow-up and comparative analysis.

    PubMed

    Odigwe, L; Sherman, P M; Filler, R; Shandling, B; Wesson, D

    1987-01-01

    We compared the postoperative course in children and teenagers who underwent subtotal colectomy, mucosal proctectomy, and either straight ileoanal anastomosis (group 1, n = 8) or ileal pouch-anal anastomosis (group 2, n = 10) for the surgical treatment of idiopathic ulcerative colitis (n = 15) and familial polyposis coli (n = 3). Two of eight children in group 1 developed intractable diarrhea that persisted despite revision of the anastomosis to include an ileal pouch; therefore, ileostomies were necessary in both cases. One patient in group 2 had a diverting ileostomy as a result of abscess formation at the site of the ileoanal anastomosis. Despite a longer period of postoperative follow-up (48.9 +/- 11.8 months), the remaining six patients in group 1 had a significantly greater number of bowel movements each day (7.8 +/- 6.5) as compared with the nine patients in group 2 who had 4.8 +/- 2.6 stools each day (p less than 0.05) at a mean follow-up of 15.7 +/- 9.0 months. A proportion of children in both groups had a poor postoperative functional outcome as determined by fecal incontinence (2 of 6 in group 1, 6 of 9 in group 2), perianal dermatitis (2 of 6, 4 of 9), and therapy with the antidiarrheal agent loperamide (4 of 6, 2 of 9). Increased school attendance (5 of 6, 7 of 7) and improvement in level of participation in social activities (5 of 6, 7 of 7) as compared with the 6-month period prior to surgery occurred, however, for most of the children with ulcerative colitis in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2828594

  3. Simultaneous analysis of reduced glutathione and glutathione disulfide by capillary zone electrophoresis.

    PubMed

    Hempe, James M; Ory-Ascani, Jeannine

    2014-04-01

    This report describes modifications to a CZE method developed by Serru et al. (Clinical Chemistry 2001, 47, 1321-1324) for the simultaneous analysis of reduced glutathione (GSH) and glutathione disulfide (GSSG). Lowering the pH of the run buffer (75 mmol/L boric acid, 25 mmol/L bis-Tris) from pH 8.4 to 7.8 markedly improved GSH peak area reproducibility and allowed multiple samples to be analyzed without changing run buffers due to ion depletion. Sample preparation using red blood cells (RBC) instead of whole blood, combined with glutathione extraction at a lower concentration of metaphosphoric acid (5%), increased assay sensitivity and decreased interference. CZE assay results for clinical samples containing 1000 to 3200 ?mol GSH/L RBC and 100 to 400 ?mol GSSG/L RBC were highly correlated (r(2) ? 0.95) with results obtained using a commercial dithionitrobenze-based glutathione assay. The modified CZE assay has proven useful for the analysis of glutathione in both mouse and human RBC. PMID:24338531

  4. Bladder agenesis and incomplete kidney duplication: Ileal reservoir with continent diversion as definitive treatment

    PubMed Central

    Pacheco-Mendoza, Byron Alexis; González-Ledón, Fernando J.; Díaz-Pardo, Mario; Soto-Blanquel, Juan L.; Castelán-Martínez, Osvaldo Daniel

    2015-01-01

    Bladder agenesis is an extremely rare entity. A 12-year-old female patient presented with urinary incontinence, recurrent urinary tract infections, visible vaginal introitus and urethra, and two holes at the vulvar vestibule. An investigation revealed bladder agenesis. Surgery confirmed the absence of bladder, and ileal reservoir in omega (?) was performed with continent diversion. At the 30-month follow-up, there was no complication in clean intermittent catheterization.

  5. Ileal digestibility of amino acids in meat meal and soybean meal fed to growing pigs.

    PubMed

    Kong, C; Kang, H G; Kim, B G; Kim, K H

    2014-07-01

    The objective of this experiment was to determine the concentration and digestibility of crude protein (CP) and amino acid (AA) in meat meal (MM), and to compare these values with the respective values in soybean meal (SBM). Six barrows (initial body weight = 66.9±3.8 kg) surgically fitted with a T-cannula at the distal ileum were allotted to a replicated 3×3 balanced Latin square design with 3 diets and 3 periods. Two experimental diets containing test ingredients as the sole source of AA were prepared to estimate the apparent ileal digestibility (AID) for CP and AA by the direct method. An N-free diet was also prepared to estimate basal endogenous losses of CP and AA. All experimental diets contained 5% chromic oxide as an indigestible index. Each period consisted of a 5-d adaptation period and a 2-d of ileal digesta collection period. Ileal digesta samples were collected from 0900 to 1700 on d 6 and 7 of each period. The concentrations of CP, Lys, Met, and Trp in MM and SBM were analyzed to be 64.1, 3.5, 1.1 and 0.6, and 45.6, 2.8, 0.8, and 0.3%, respectively. The AID of all AA except Gly in MM was less (p<0.05) than in SBM. The AID of Lys, Met, and Trp in MM was estimated to be 56.0, 71.7, and 47.1%, respectively. The SID of all AA in MM was less (p<0.05) than in SBM. The SID of Lys, Met, and Trp was 65.1, 79.2, and 78.5%, respectively. In conclusion, the CP and AA contents in MM were greater than those in SBM whereas the ileal digestibility of all AA in MM was less than in SBM. PMID:25050041

  6. Comparison of standardized ileal amino acid digestibilities in protein supplements and cereal grains for weaned pigs.

    PubMed

    Sauer, N; Eklund, M; Hoerner, S; Rademacher, M; Mosenthin, R

    2012-12-01

    Standardized ileal digestibility (SID) of AA in protein ingredients and grains was determined in weaned piglets (5 kg initial BW) using the difference method. Animals were fitted with a simple ileal T-cannula on day 24 or 25 of age. A synthetic diet based on corn (Zea mays) starch and casein was either supplemented with an extruded soybean (Glycine max) meal (ESM), rice (Oryza sativa) protein concentrate (RPC), full fat heat-treated soybeans (SB), corn, barley (Hordeum vulgare), or wheat (Triticum aestivum). The contribution of CP and AA from casein and from the assay feed ingredients to the assay diet averaged 50% each. Each diet was fed to 6 animals according to a row-column design with 3 periods. Apparent ileal digestibility was corrected for basal ileal endogenous losses of AA to obtain SID values. Between RPC and soy products, differences (P < 0.05) in SID of most AA such as Lys, Met, and Thr were greater than within soybean products (ESM and SB). The SID of indispensable AA did not differ (P > 0.05) between barley and wheat, except for Met (P < 0.05). Furthermore, SID of Arg, His, Ile, Phe, and Trp was lower (P < 0.05) in corn than wheat. In conclusion, SID of most AA in the present study with piglets was lower than tabulated SID values determined in studies with grower-finisher pigs. Furthermore, the use of RPC, despite its high CP content, in diets for weaned piglets is limited due to its low SID of AA. PMID:23365298

  7. The Mycotoxin Deoxynivalenol Potentiates Intestinal Inflammation by Salmonella Typhimurium in Porcine Ileal Loops

    Microsoft Academic Search

    Virginie Vandenbroucke; Siska Croubels; An Martel; Elin Verbrugghe; Joline Goossens; Kim Van Deun; Filip Boyen; Arthur Thompson; Neil Shearer; Patrick De Backer; Freddy Haesebrouck; Frank Pasmans

    2011-01-01

    Background and AimsBoth deoxynivalenol (DON) and nontyphoidal salmonellosis are emerging threats with possible hazardous effects on both human and animal health. The objective of this study was to examine whether DON at low but relevant concentrations interacts with the intestinal inflammation induced by Salmonella Typhimurium.MethodologyBy using a porcine intestinal ileal loop model, we investigated whether intake of low concentrations of

  8. Ileal Digestibility of Amino Acids in Meat Meal and Soybean Meal Fed to Growing Pigs

    PubMed Central

    Kong, C.; Kang, H. G.; Kim, B. G.; Kim, K. H.

    2014-01-01

    The objective of this experiment was to determine the concentration and digestibility of crude protein (CP) and amino acid (AA) in meat meal (MM), and to compare these values with the respective values in soybean meal (SBM). Six barrows (initial body weight = 66.9±3.8 kg) surgically fitted with a T-cannula at the distal ileum were allotted to a replicated 3×3 balanced Latin square design with 3 diets and 3 periods. Two experimental diets containing test ingredients as the sole source of AA were prepared to estimate the apparent ileal digestibility (AID) for CP and AA by the direct method. An N-free diet was also prepared to estimate basal endogenous losses of CP and AA. All experimental diets contained 5% chromic oxide as an indigestible index. Each period consisted of a 5-d adaptation period and a 2-d of ileal digesta collection period. Ileal digesta samples were collected from 0900 to 1700 on d 6 and 7 of each period. The concentrations of CP, Lys, Met, and Trp in MM and SBM were analyzed to be 64.1, 3.5, 1.1 and 0.6, and 45.6, 2.8, 0.8, and 0.3%, respectively. The AID of all AA except Gly in MM was less (p<0.05) than in SBM. The AID of Lys, Met, and Trp in MM was estimated to be 56.0, 71.7, and 47.1%, respectively. The SID of all AA in MM was less (p<0.05) than in SBM. The SID of Lys, Met, and Trp was 65.1, 79.2, and 78.5%, respectively. In conclusion, the CP and AA contents in MM were greater than those in SBM whereas the ileal digestibility of all AA in MM was less than in SBM. PMID:25050041

  9. Bladder agenesis and incomplete kidney duplication: Ileal reservoir with continent diversion as definitive treatment.

    PubMed

    Pacheco-Mendoza, Byron Alexis; González-Ledón, Fernando J; Díaz-Pardo, Mario; Soto-Blanquel, Juan L; Castelán-Martínez, Osvaldo Daniel

    2015-01-01

    Bladder agenesis is an extremely rare entity. A 12-year-old female patient presented with urinary incontinence, recurrent urinary tract infections, visible vaginal introitus and urethra, and two holes at the vulvar vestibule. An investigation revealed bladder agenesis. Surgery confirmed the absence of bladder, and ileal reservoir in omega (?) was performed with continent diversion. At the 30-month follow-up, there was no complication in clean intermittent catheterization. PMID:25844102

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  11. Laparoscopic radical cystoprostatectomy with ileal conduit performed completely intracorporeally: the initial 2 cases

    Microsoft Academic Search

    Inderbir S Gill; Amr Fergany; Eric A Klein; Jihad H Kaouk; Gyung Tak Sung; Anoop M Meraney; Stephen J Savage; James C Ulchaker; Andrew C Novick

    2000-01-01

    Objectives. To present the initial 2 patients who underwent laparoscopic radical cystoprostatectomy, bilateral pelvic lymphadenectomy, and ileal conduit urinary diversion, with the entire procedure performed exclusively by intracorporeal laparoscopic techniques.Methods. Two male patients, 78 and 70 years old, with muscle-invasive, organ-confined, transitional cell carcinoma of the urinary bladder underwent the procedure. The entire procedure, including radical cystoprostatectomy, pelvic node dissection,

  12. Orthotopic bladder substitution following radical cystectomy in women: comparative study between sigmoid and ileal neobladders.

    PubMed

    Miyake, Hideaki; Furukawa, Junya; Muramaki, Mototsugu; Takenaka, Atsushi; Fujisawa, Masato

    2012-01-01

    The objective of this study was to retrospectively compare the clinical outcomes of sigmoid and ileal neobladders (NBs) created in women. This study included 18 and 14 women who underwent orthotopic NB reconstruction using sigmoid and ileal segment, respectively, after radical cystectomy, and postoperative clinical outcomes between the sigmoid and ileal NB groups (SNBG and INBG) were compared. Eighteen early and 7 late complications occurred in 12 and 6 women, respectively; however, there was no significant difference in the incidence of complications between SNBG and INBG. The proportion of patients who could void spontaneously in SNBG (94.4%) was significantly greater than that in INBG (64.3%), while there was no significant difference in continent status between these 2 groups. Despite the lack of significant differences in maximal flow rate and voided volume, post-void residual in SNBG (15.7 ml) was significantly smaller than that in INBG (62.0 ml). SF-36 survey for postoperative quality of life (QOL) did not show any significant differences in 7 of the 8 scores between the 32 women with NB and an age-matched control population; however, 3 of the 8 scores in SNBG were significantly superior to those in INBG. During the observation period of this study, urethral recurrence did not occur in any woman, and there was no significant difference in cancer-specific survival between the 2 groups. These findings suggest that it might be preferable to create sigmoid rather than ileal NB in women following radical cystectomy considering the favorable voiding function and QOL in SNBG. PMID:20056456

  13. Molecular ecological analysis of porcine ileal microbiota responses to antimicrobial growth promoters1

    Microsoft Academic Search

    C. T. Collier; M. R. Smiricky-Tjardes; D. M. Albin; J. E. Wubben; V. M. Gabert; B. Deplancke; D. Bane; D. B. Anderson; H. R. Gaskins

    Cultivation-independent microbial mo- lecular ecology approaches were used to examine the effects of antibiotic growth promoters on the pig ileal microbiota. Five-week-old barrows were fitted with a simple T-cannula at the distal ileum. Three diets meet- ing or exceeding the minimum nutrient requirements were fed for 5 wk and supplemented as follows: 1) nega- tive control (no antibiotic; n =

  14. Down-regulation of mechanisms involved in cell transport and maintenance of mucosal integrity in pigs infected with Lawsonia intracellularis

    PubMed Central

    2014-01-01

    Lawsonia intracellularis is an obligate intracellular bacterium, responsible for the disease complex known as proliferative enteropathy (PE). L. intracellularis is associated with intestinal crypt epithelial cell proliferation but the mechanisms responsible are yet to be defined. Microarray analysis was used to investigate the host-pathogen interaction in experimentally infected pigs to identify pathways that may be involved. Ileal samples originating from twenty-eight weaner pigs experimentally challenged with a pure culture of L. intracellularis (strain LR189/5/83) were subjected to microarray analysis. Microarray transcriptional signatures were validated using immunohistochemistry and quantitative real time PCR of selected genes at various time points post challenge. At peak of infection (14 days post challenge) 86% of altered transcripts were down regulated, particularly those involved in maintenance of mucosal integrity and regulation of cell transport. Among the up-regulated transcripts, CD163 and CDK1 were novel findings and considered to be important, due to their respective roles in innate immunity and cellular proliferation. Overall, targeted cellular mechanisms included those that are important in epithelial restitution, migration and protection; maintenance of stable inter-epithelial cell relationships; cell transport of nutrients and electrolytes; innate immunity; and cell cycle. PMID:24885874

  15. Down-regulation of mechanisms involved in cell transport and maintenance of mucosal integrity in pigs infected with Lawsonia intracellularis.

    PubMed

    Smith, Sionagh H; Wilson, Alison D; Van Ettinger, Imke; MacIntyre, Neil; Archibald, Alan L; Ait-Ali, Tahar

    2014-01-01

    Lawsonia intracellularis is an obligate intracellular bacterium, responsible for the disease complex known as proliferative enteropathy (PE). L. intracellularis is associated with intestinal crypt epithelial cell proliferation but the mechanisms responsible are yet to be defined. Microarray analysis was used to investigate the host-pathogen interaction in experimentally infected pigs to identify pathways that may be involved. Ileal samples originating from twenty-eight weaner pigs experimentally challenged with a pure culture of L. intracellularis (strain LR189/5/83) were subjected to microarray analysis. Microarray transcriptional signatures were validated using immunohistochemistry and quantitative real time PCR of selected genes at various time points post challenge. At peak of infection (14 days post challenge) 86% of altered transcripts were down regulated, particularly those involved in maintenance of mucosal integrity and regulation of cell transport. Among the up-regulated transcripts, CD163 and CDK1 were novel findings and considered to be important, due to their respective roles in innate immunity and cellular proliferation. Overall, targeted cellular mechanisms included those that are important in epithelial restitution, migration and protection; maintenance of stable inter-epithelial cell relationships; cell transport of nutrients and electrolytes; innate immunity; and cell cycle. PMID:24885874

  16. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis

    Microsoft Academic Search

    C Penna; R Dozois; W Tremaine; W Sandborn; N LaRusso; C Schleck; D Ilstrup

    1996-01-01

    Primary sclerosing cholangitis (PSC), present in 5% of patients with ulcerative colitis, may be associated with pouchitis after ileal pouch-anal anastomosis. The cumulative frequency of pouchitis in patients with and without PSC who underwent ileal pouch-anal anastomosis for ulcerative colitis was determined. A total of 1097 patients who had an ileal pouch-anal anastomosis for ulcerative colitis, 54 with associated PSC,

  17. Laparoscopic radical cystectomy: neobladder or ileal conduit, debate still goes on

    PubMed Central

    Drewa, Tomasz; Olejniczak, Pawel; Chlosta, Piotr L.

    2014-01-01

    Objective To compare the pre, intra, and post–operative data between ileal conduit and neobladder urinary diversions during laparoscopic radical cystectomy(LRC). Material and methods Between 2006 and 2011, 63 patients who underwent LRC and urinary diversion had their data input prospectively into a database and said data used for the analysis. The outcome comparators were the patient demographics, operative time, conversion rate, blood loss, transfusion rate, morphine analgesic requirement, length of hospital stay, complication rates, follow up, and quality of life assessments. A Mantel–Haenszel test was used for dichotomous data and an inverse variance method was used for continuous data. P values less than 0.5 were considered significant Results Thirty–nine patients (60 ±7.11 years) had ileal conduits and 24 patients (57 ±8.68 years) had neobladder urinary diversion. No difference was found (P >0.05) regarding age, BMI, smoking history, TURBT pathology result, blood loss, blood transfusion requirement, conversion rates, length of hospital stay, morphine requirement, complications, or follow–up and quality of life. The neobladder groups did have more previous abdominal operations and had significantly longer operative time. Conclusions We found no difference between either types of diversion in all comparative aspects except that the neobladder had longer operative times. This is the first comparative study between ileal conduit and neobladder urinary diversion after laparoscopic radical cystectomy and can pose as a bench mark for future comparisons. PMID:24982773

  18. Temporal variations of the ileal microbiota in intestinal ischemia and reperfusion.

    PubMed

    Wang, Fan; Li, Qiurong; He, Qi; Geng, Yanxia; Tang, Chun; Wang, Chenyang; Li, Jieshou

    2013-01-01

    Gastrointestinal bacteria and epithelia contribute to systemic inflammation and infections in critically ill patients, but the gut microbiota in these diseases has not been analyzed dynamically by molecular fingerprinting methods. This study aimed to identify ileal flora dysbiosis pattern and bacterial species that changed significantly in a rat model of intestinal ischemia and reperfusion and illustrate time courses of both epithelial alterations and gut flora variations in the same injury. Forty-eight rats were randomized into eight groups (n = 6/group). Six groups underwent superior mesenteric artery occlusion for 30 min and were killed at 1, 3, 6, 12, 24, and 72 h following reperfusion, respectively; a group of rats were killed just after anesthesia (control), and a sham-operated group received 12-h reperfusion. Denaturing gradient gel electrophoresis of ileal microbiota showed that gut flora pattern changed early after intestinal ischemia and reperfusion, differed significantly at 12 h of reperfusion, and then started to recover toward normal pattern. The specific dysbiosis were characterized by Escherichia coli proliferation and Lachnospiraceae and Lactobacilli reduction. These bacteria that contributed most were identified by principal component analysis and sequencing and confirmed by real-time polymerase chain reaction. In addition, alterations of ileal microbiota followed epithelial changes in the time course of reperfusion. PMID:23247126

  19. The effect of ileal bypass on sterol balance and plasma cholesterol in the White Carneau pigeon.

    PubMed

    Flynn, K J; Schumacher, J F; Subbiah, M T; Kottke, B A

    1976-01-01

    The effect of ileal bypass on steady-state sterol balance and plasma cholesterol was studied in sham operated (SO) and ileal bypass (IB) White Carneau pigeons 6 months (Group I) and 18 months (Group II) after surgery while fed their usual cholesterol-free diet. Unlike what has been noted in other animals, the bile acid (BA) and neutral sterol (NS) excretion (mg/kg per day) in IB was not statistically different from that in SO. Group I: BA, 40.2 (SO) vs 39.0 (IB); NS, 13.3 (SO) vs 17.3 (IB). Group II: BA, 55.7 (SO) vs 54.1 (IB); NS, 9.57 (SO) vs 8.84 (IB). IB pigeons had only slightly lower plasma cholesterol levels (postoperative) than SO pigeons. Group I, 329 (SO) vs 271 (IB) mg/dl (P less than 0.05); Group II, 374 (SO) vs 312 (IB) mg/dl. This study indicates that the response to ileal bypass by White Carneau pigeons in terms of cholesterol excretion and plasma cholesterol changes is different than what has been observed in other species. PMID:942529

  20. Inhibition of soluble glutathione S-transferase by diuretic drugs.

    PubMed

    Ahokas, J T; Davies, C; Ravenscroft, P J; Emmerson, B T

    1984-06-15

    Glutathione transferases are believed to play an important protective role in the various tissues of animals and man by catalysing the glutathione conjugation of electrophilic drugs and electrophilic drug metabolites. Many of these compounds have the potential to react with vital cellular macromolecules in the absence of this enzyme system. We have investigated the interaction of a number of high ceiling diuretics with the glutathione transferases contained in the cytosolic fraction of the rat liver. Of bumetanide, ethacrynic acid, furosemide, indacrynic acid and tienilic acid, only ethacrynic acid was conjugated with glutathione. Further experiments revealed that ethacrynic, indacrynic and tienilic acids are all potent inhibitors of glutathione S- aryltransferase . Glutathione S- alkyltransferase and glutathione S-epoxide transferase were also inhibited by the diuretics, but to a lesser extent than glutathione S- aryltransferase . The diuretics giving the greatest inhibition of these reactions were chemically related to ethacrynic acid. The concept where inhibition of glutathione-S-transferase by a drug may enhance its own toxicity is considered. This mechanism has also the potential of enhancing the toxicity of other concurrently administered drugs which normally require glutathione S-transferase for detoxication. PMID:6732850

  1. Mucosal cavernous hemangioma of the maxillary sinus.

    PubMed

    Dutta, Mainak; Kundu, Sohag; Barik, Sabyasachi; Banerjee, Shoham; Mukhopadhyay, Subrata

    2015-02-01

    Mucosal cavernous hemangiomas of maxillary sinus and the lateral nasal wall are seldom encountered and difficult to diagnose with misleading radiologic features like bone erosion and heterogeneity due to patchy contrast uptake. The overall picture mimicking sinonasal malignancy, it is unclear whether there is true breach in the bone or remodeling due to the lesion's chronicity. Interestingly, it often does not bleed as expected during surgery, questioning the use of therapeutic embolization and pre-intervention vascular shrinkage. The clinical presentation and management protocol of sinonasal cavernous hemangiomas seem greatly individualized. We here present a patient with cavernous hemangioma of maxillary sinus and discuss the distinguishing clinical, histologic and imaging characteristics and subsequent management options, and attempt to establish the findings as the basis of considering it as an important differential diagnosis of radiologically heterogeneous sinonasal mass with suspected bone erosions presenting with nasal obstruction and epistaxis, mostly in young women. PMID:25644804

  2. Rectal mucosal dysplasia in Crohn's disease.

    PubMed Central

    Korelitz, B I; Lauwers, G Y; Sommers, S C

    1990-01-01

    Serial sections of 812 rectal biopsy specimens from 356 Crohn's disease patients were analysed for mucosal epithelial dysplasia. Dysplasia was found in 18 patients (5%), with four showing dysplasia on repeat biopsy specimen. In these 22 biopsy specimens the dysplasia was mild in 13, moderate in nine, and severe in none. Subsequently, three patients (17%) developed neoplasms including carcinoma in two and an adenomatous polyp in one. In colectomy specimens which showed dysplasia, significantly more dysplastic changes were found in seven patients who underwent colonic resection than in 10 others who underwent operation but had no prior dysplasia (p less than 0.001). Thirteen patients still have their rectum in situ and remain at risk of developing colonic cancer. Four carcinomas developed in patients with Crohn's disease who did not have dysplasia on rectal biopsy specimen. Images Figure 1 Figure 2 PMID:2265778

  3. Oral mucosal morphea: a new variant.

    PubMed

    Tang, M M; Bornstein, M M; Irla, N; Beltraminelli, H; Lombardi, T; Borradori, L

    2012-01-01

    Morphea is a cutaneous disorder characterized by an excessive collagen deposition. While in almost all cases the sclerosing process exclusively affects the skin, there are anecdotal cases in which associated mucosal involvement has been described. We here report the case of a woman developing a whitish indurated plaque over the left upper vestibular mucosa and hard palate leading to dental mobility and exposure of the roots of several teeth. Cone beam computed tomography of the left maxilla showed bone resorption involving the upper cuspid to the second molar region with widened periodontal ligament spaces, while light microscopy studies demonstrated epithelial atrophy and fibrosis of the dermis extending into the submucosa with hyalinization of subepithelial collagen. Our observation expands the spectrum of clinical presentations of morphea and provides the first example of isolated oral morphea. Its recognition is important to avoid significant local complications. PMID:22538799

  4. 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. PMID:25196917

  5. The oral mucosal surface and blood vessels

    PubMed Central

    2013-01-01

    Introduction Detailed information about the size of the oral mucosa is scarce in the literature, and those studies that do exist do not take into account the size of the tongue or the enlargement of the surface by the papillae. Because of the various functions of the oral mucosa in the maintenance of oral health, knowledge of its true size may provide a better understanding of the physiology of the oral cavity and some oral diseases and direct future therapeutic strategies. The aim of this study was to determine the total size of the oral mucosa. Methods Five human adult cadaver heads were cut in the median sagittal plane, and the total area of the oral surface was determined using silicon casts. The surface of the tongue was measured with quantitative profilometry. Photographs of oral blood vessels were taken in different areas of the oral mucosa of adult test subjects using intravital microscopy, and the pictures were compared with vessel casts of the oral mucosal capillaries of a maccaca fasciculrais monkey, which was studied using a scanning electron microscope. Results The results showed that the dorsal side of the tongue comprises a large proportion of the total oral mucosal surface. The surface area of the epithelium increases moving from anterior to posterior on the tongue, and the number of underlying blood vessels increases proportionally. Conclusions It can be concluded that the back of the tongue plays an important role in the oral resorption of drugs. Clinical relevance: The results may be of relevance for the delivery and development of oral drug application. PMID:23497446

  6. Microbes and mucosal immune responses in asthma.

    PubMed

    Hansel, Trevor T; Johnston, Sebastian L; Openshaw, Peter J

    2013-03-01

    The substantial increase in the worldwide prevalence of asthma and atopy has been attributed to lifestyle changes that reduce exposure to bacteria. A recent insight is that the largely bacterial microbiome maintains a state of basal immune homoeostasis, which modulates immune responses to microbial pathogens. However, some respiratory viral infections cause bronchiolitis of infancy and childhood wheeze, and can exacerbate established asthma; whereas allergens can partly mimic infectious agents. New insights into the host’s innate sensing systems, combined with recently developed methods that characterise commensal and pathogenic microbial exposure, now allow a unified theory for how microbes cause mucosal inflammation in asthma. The respiratory mucosa provides a key microbial interface where epithelial and dendritic cells interact with a range of functionally distinct lymphocytes. Lymphoid cells then control a range of pathways, both innate and specific, which organise the host mucosal immune response. Fundamental to innate immune responses to microbes are the interactions between pathogen-associated molecular patterns and pattern recognition receptors, which are associated with production of type I interferons, proinflammatory cytokines, and the T-helper-2 cell pathway in predisposed people. These coordinated, dynamic immune responses underlie the differing asthma phenotypes, which we delineate in terms of Seven Ages of Asthma. An understanding of the role of microbes in the atopic march towards asthma, and in causing exacerbations of established asthma, provides the rationale for new specific treatments that can be assessed in clinical trials. On the basis of these new ideas, specific host biomarkers might then allow personalised treatment to become a reality for patients with asthma. PMID:23428115

  7. Th17 cytokines in mucosal immunity and inflammation

    PubMed Central

    Guglani, Lokesh; Khader, Shabaana A.

    2010-01-01

    Purpose of the review Compelling evidence suggests that the Th17 lineage and other IL-17 producing cells play critical roles in host defense against pathogens at mucosal sites. However, IL-17 can also contribute to inflammatory responses at mucosal sites. In this review, we will discuss the recent progress in our understanding of the role of Th17 and other IL-17-producing cells in defining the fine balance between immunity and inflammation at different mucosal sites. Recent Findings Recent findings have highlighted that Th17 cytokines are important for the induction of innate and adaptive host responses and contribute to host defense against pathogens at mucosal sites. More recent developments have probed how the Th17 responses are generated in vivo in response to infections and their requirement in maintaining barrier function at mucosal sites. Most importantly, it is becoming apparent that there is a fine balance between protective and pathological manifestation of Th17 responses at mucosal sites that defines immunity or inflammation. Summary In this review we have summarized the recent advances in our understanding of Th17 cytokines and how they contribute to immunity versus inflammation at mucosal sites. PMID:20543588

  8. Modeling mucosal candidiasis in larval zebrafish by swimbladder injection.

    PubMed

    Gratacap, Remi L; Bergeron, Audrey C; Wheeler, Robert T

    2014-01-01

    Early defense against mucosal pathogens consists of both an epithelial barrier and innate immune cells. The immunocompetency of both, and their intercommunication, are paramount for the protection against infections. The interactions of epithelial and innate immune cells with a pathogen are best investigated in vivo, where complex behavior unfolds over time and space. However, existing models do not allow for easy spatio-temporal imaging of the battle with pathogens at the mucosal level. The model developed here creates a mucosal infection by direct injection of the fungal pathogen, Candida albicans, into the swimbladder of juvenile zebrafish. The resulting infection enables high-resolution imaging of epithelial and innate immune cell behavior throughout the development of mucosal disease. The versatility of this method allows for interrogation of the host to probe the detailed sequence of immune events leading to phagocyte recruitment and to examine the roles of particular cell types and molecular pathways in protection. In addition, the behavior of the pathogen as a function of immune attack can be imaged simultaneously by using fluorescent protein-expressing C. albicans. Increased spatial resolution of the host-pathogen interaction is also possible using the described rapid swimbladder dissection technique. The mucosal infection model described here is straightforward and highly reproducible, making it a valuable tool for the study of mucosal candidiasis. This system may also be broadly translatable to other mucosal pathogens such as mycobacterial, bacterial or viral microbes that normally infect through epithelial surfaces. PMID:25490695

  9. Dental students' ability to detect and diagnose oral mucosal lesions.

    PubMed

    Ali, Mohammad A; Joseph, Bobby K; Sundaram, Devipriya B

    2015-02-01

    The aim of this study was to assess the ability of dental students in the screening clinic of the Kuwait University Dental Center to detect and diagnose oral mucosal lesions. Clinical examinations performed by dental students between January 2009 and February 2011 were included. All their findings regarding the oral mucosal lesions and dental carious lesions detected were recorded, after which the patients were re-examined by faculty examiners. The students rated their own ability to detect mucosal and carious lesions before each examination. Among the 341 patients screened, 375 oral mucosal lesions were found by the faculty examiners. Of those, the students detected 178 (47.5%). Out of the 375 lesions, including the ones they failed to detect, the students diagnosed 272 (72.5%) correctly. The students were more likely (p?0.01) to correctly diagnose a mucosal lesion when they themselves had detected it (n=169/178) than when they failed to detect it and had it subsequently pointed out by the faculty examiners (n=103/197). The students were more competent in detecting carious lesions (p?0.001) than in detecting mucosal lesions. A significantly higher proportion of students who felt confident in detecting mucosal lesions were actually more competent in detecting the lesions than those who were not confident (p?0.001). Further educational strategies are needed to motivate Kuwait University dental students to develop the knowledge, skills, and judgment necessary to integrate a complete intraoral examination into their routine practice. PMID:25640618

  10. Roles of Mucosal Immunity against Mycobacterium tuberculosis Infection.

    PubMed

    Li, Wu; Deng, Guangcun; Li, Min; Liu, Xiaoming; Wang, Yujiong

    2012-01-01

    Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is one of the world's leading infectious causes of morbidity and mortality. As a mucosal-transmitted pathogen, Mtb infects humans and animals mainly through the mucosal tissue of the respiratory tract. Apart from providing a physical barrier against the invasion of pathogen, the major function of the respiratory mucosa may be to serve as the inductive sites to initiate mucosal immune responses and sequentially provide the first line of defense for the host to defend against this pathogen. A large body of studies in the animals and humans have demonstrated that the mucosal immune system, rather than the systemic immune system, plays fundamental roles in the host's defense against Mtb infection. Therefore, the development of new vaccines and novel delivery routes capable of directly inducing respiratory mucosal immunity is emphasized for achieving enhanced protection from Mtb infection. In this paper, we outline the current state of knowledge regarding the mucosal immunity against Mtb infection, including the development of TB vaccines, and respiratory delivery routes to enhance mucosal immunity are discussed. PMID:23213508

  11. Oral mucosal status and major salivary gland function

    SciTech Connect

    Wolff, A.; Fox, P.C.; Ship, J.A.; Atkinson, J.C.; Macynski, A.A.; Baum, B.J. (National Institute of Dental Research, Bethesda, MD (USA))

    1990-07-01

    Normal salivary function is considered to be critical for the maintenance of healthy oral mucosa. However, few studies have examined mucosal changes in patients with objectively documented salivary gland performance. In the present report, the mucosal status of 298 subjects being evaluated in a dry mouth clinic was assessed. A complete oral examination was performed and unstimulated and stimulated salivary samples were collected separately from the parotid and submandibular/sublingual glands. Data were analyzed according to diagnosis and salivary output after the assignment of an oral mucosal rating to each subject. In general, the mucosal surfaces were well preserved and infections were not seen. Patients evaluated for Sjoegren's syndrome and radiation-induced xerostomia had the lowest salivary gland performance but displayed a mucosal status similar to denture-wearing healthy subjects or patients with normal salivary flow who had idiopathic xerostomia. However, those patients with a total lack of salivary flow rarely had normal-appearing oral mucosa. These results confirm a role for saliva in oral mucosal preservation and also suggest that other factors may act to maintain oral mucosal integrity.

  12. Identification of a glutathione S-transferase without affinity for glutathione sepharose in human kidney.

    PubMed

    Simic, T; Pljesa-Ercegovac, M; Savic-Radojevic, A; Hadziahmetovic, M; Mimic-Oka, J

    2006-06-01

    To identify kidney glutathione S-transferase (GST) isoenzyme, which does not bind to glutathione affinity column, biochemical characterization was performed by using an array of substrates and by measuring sensitivity to inhibitors. Immunological characterization was done by immunoblotting. Affinity flow-through GST exhibited activity towards 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole and cumene hydroperoxide, typical class alpha substrates and high sensitivity towards hematin, an alpha class inhibitor. It cross-reacted with antibodies against alpha class GST. Affinity flow-through GST in human kidney is an alpha class member. PMID:16773246

  13. Effects of concentrated drinking water injection on glutathione and glutathione-dependent enzymes in liver of Cyprinus carpio L.

    PubMed

    Elia, Antonia Concetta; Fanetti, Alessia; Dörr, Ambrosius Josef Martin; Taticchi, Maria I

    2008-06-01

    Two drinking water production plants located in North Italy, collecting water from the River Po (Plants 1 and 2) were chosen for this study. Water samples were collected before and after the disinfection process and at two points along the piping system. Water samples were concentrated by the solid-phase extraction system and injected intraperitoneally into specimens of Cyprinus carpio. The concentration of water samples was 3 l/equiv. In order to assess the effects of the water samples on carp liver, total glutathione and glutathione-dependent enzymes, such as glutathione S-transferase, glutathione peroxidase, glutathione reductase and glyoxalase I, were measured following this treatment for 6 days at two experimental times (3 and 6 days). Both water plant-treated carp showed a general increase of the enzymatic activities of glutathione S-transferase, and glutathione reductase which might be employed as potential biomarkers of oxidative stress induced by disinfected river water. Plant 1-treated carp showed higher glyoxalase I and glutathione levels and lower glutathione peroxidase activity. A depleted level of total glutathione and of glyoxalase I for specimens of water plant 2 (for both experimental times), without correlation with the distances in the pipeline, suggests that river plant water can also lead to potentially adverse effects on selected biochemical parameters in C. carpio. PMID:18457861

  14. Prevention and management of antineoplastic therapy induced oral mucositis

    PubMed Central

    Bey, Afshan; Ahmed, Syed S.; Hussain, Bilal; Devi, Seema; Hashmi, Sarwat H.

    2010-01-01

    With the scientific advancements in the management of malignant diseases, the treatment is expensive and bears high morbidity in term of oral mucositis. It is a debilitating condition and has been researched extensively for its pathogenesis and treatment. Various treatment options include barrier forming, mucosal protectants, mouth rinses, growth factors, lasers and midline-sparing procedures. Some agents are used locally while others are administered systemically. Despite the availability of a wide range of treatment options for mucositis, a cost-effective treatment is yet to be evolved. PMID:22442583

  15. Deficient Glutathione in the Pathophysiology of Mycotoxin-Related Illness

    PubMed Central

    Guilford, Frederick T.; Hope, Janette

    2014-01-01

    Evidence for the role of oxidative stress in the pathophysiology of mycotoxin-related illness is increasing. The glutathione antioxidant and detoxification systems play a major role in the antioxidant function of cells. Exposure to mycotoxins in humans requires the production of glutathione on an “as needed” basis. Research suggests that mycotoxins can decrease the formation of glutathione due to decreased gene expression of the enzymes needed to form glutathione. Mycotoxin-related compromise of glutathione production can result in an excess of oxidative stress that leads to tissue damage and systemic illness. The review discusses the mechanisms by which mycotoxin-related deficiency of glutathione may lead to both acute and chronic illnesses. PMID:24517907

  16. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1365 Glutathione test system. (a) Identification....

  17. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1365 Glutathione test system. (a) Identification....

  18. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1365 Glutathione test system. (a) Identification....

  19. Purified ?-Glutamyl Transpeptidases from Tomato Exhibit High Affinity for Glutathione and Glutathione S-Conjugates1

    PubMed Central

    Martin, Melinda Neal; Slovin, Janet P.

    2000-01-01

    ?-Glutamyl transpeptidases (?GTases) are the only enzymes known to hydrolyze the unique N-terminal amide bonds of reduced glutathione (?-l-glutamyl-cysteinyl-glycine), oxidized glutathione, and glutathione S-conjugates. Two ?GTases (I and II) with Km values for glutathione of 110 and 90 ?m were purified 2,977-fold and 2,152-fold, respectively, from ripe tomato (Lycopersicon esculentum) pericarp. Both enzymes also hydrolyze dipeptides and other tripeptides with N-terminal, ?-linked Glu and the artificial substrates ?-l-glutamyl-p-nitroanilide and ?-l-glutamyl(7-amido-4-methylcoumarin). They transfer the glutamyl moiety to water or acceptor amino acids, including l-Met, l-Phe, l-Trp, l-Ala, or the ethylene precursor 1-aminocyclopropane-1-carboxylic acid. ?GTase I and II were released from a wall and membrane fraction of a tomato fruit extract with 1.0 m NaCl, suggesting that they are peripheral membrane proteins. They were further purified by acetone precipitation, Dye Matrex Green A affinity chromatography, and hydrophobic interaction chromatography. The two ?GTases were resolved by concanavalin A (Con A) affinity chromatography, indicating that they are differentially glycosylated. The native and SDS-denatured forms of both enzymes showed molecular masses of 43 kD. PMID:10759537

  20. GLUTATHIONE PEROXIDASE AND GLUTATHIONE TRANSFERASE ACTIVITY IN RAT LUNG AND LIVER FOLLOWING CADMIUM INHALATION

    EPA Science Inventory

    A 2 hr inhalation exposure to 4.6 mg Cd/cu m decreased pulmonary total glutathione peroxidase (GSH Px) activity and non-selenium peroxidase (GSH non-Se-Px) activity but had no effect on GSH selenium peroxidase (Se-Px) activity. Seventy-two hrs after exposure there was an increase...

  1. 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

  2. Laparoscopic management of an octogenarian adult intussusception caused by an ileal lipoma suspected preoperatively: a case report.

    PubMed

    Shimazaki, Jiro; Nakachi, Takeshi; Tabuchi, Takanobu; Suzuki, Shuji; Ubukata, Hideyuki; Tabuchi, Takafumi

    2015-12-01

    Adult intussusception is rare and usually caused by a tumor acting as the lead point. Therefore, laparotomy should be considered for the treatment. Laparoscopic procedures for use in cases of adult intussusception have been recently reported; however, there is no consensus regarding the safety and efficacy. Here, we describe a successful case of laparoscopic management of an octogenarian adult intussusception caused by an ileal lipoma, which was preoperatively suspected. An 87-year-old male presented with progressive abdominal distention and vomiting. Contrast radiography of the small intestine showed an ileal tumor, and magnetic resonance imaging indicated a target-like mass, consistent with an ileal intussusception. The patient was suspected with an intussusception due to an ileal lipoma, and laparoscopic surgery was performed. An approximately 10-cm-long ileal intussusception with a preceding tumor was present, and partial resection of the ileum, including the tumor, was performed. Macroscopic examination of the excised specimen showed a pedunculated tumor measuring 4.0?×?3.5?×?1.9 cm with an uneven surface, yielding a histological diagnosis of lipoma. The patient had an uneventful recovery and was discharged on postoperative day 8. This successful case showed that laparoscopic surgery can be a useful, safe, and efficacious procedure for adult intussusception, even in octogenarians. PMID:25778073

  3. Cloning and molecular characterization of the ontogeny of a rat ileal sodium-dependent bile acid transporter.

    PubMed Central

    Shneider, B L; Dawson, P A; Christie, D M; Hardikar, W; Wong, M H; Suchy, F J

    1995-01-01

    Sodium-dependent bile acid transport in the rat ileum is abruptly expressed at weaning. Degenerate oligonucleotides, based on amino acid sequence identities between the rat liver and hamster ileal transporters, were used to amplify a rat ileal probe. A 1.2-kb cDNA clone, which contains the full coding region (348 amino acids, 38 kD), was isolated by hybridization screening. In vitro translation yielded a 38-kD protein which glycosylated to 48 kD. Sodium-dependent uptake of taurocholate was observed in oocytes injected with cRNA. Northern blot analysis revealed a 5.0-kb mRNA in ileum, kidney, and cecum. A 48-kD protein was detected in ileal brush border membranes and localized to the apical border of villus ileal enterocytes. mRNA and protein expression, which were negligible before weaning, increased dramatically at weaning. Nuclear transcription rates for the transporter increased 15-fold between postnatal days 7 and 28. The apparent molecular weight of the transporter also increased between days 19 and 28. In summary, the developmental regulation of the rat ileal sodium-dependent bile acid cotransporter is characterized by transcriptionally regulated increases in mRNA and protein levels at the time of weaning with changes in apparent molecular weight of the protein after weaning. Images PMID:7860756

  4. Glutathione transferase omega 1 catalyzes the reduction of S-(phenacyl)glutathiones to acetophenones.

    PubMed

    Board, Philip G; Anders, M W

    2007-01-01

    S-(Phenacyl)glutathione reductase (SPG-R) plays a significant role in the biotransformation of reactive alpha-haloketones to nontoxic acetophenones. Comparison of the apparent subunit size, amino acid composition, and catalysis of the reduction of S-(phenacyl)glutathiones indicated that a previously described rat SPG-R (Kitada, M., McLenithan, J. C., and Anders, M. W. (1985) J. Biol. Chem. 260, 11749-11754) is homologous to the omega-class glutathione transferase GSTO1-1. The available data show that the SPG-R reaction is catalyzed by GSTO1-1 and not by other GSTs, including the closely related GSTO2-2 isoenzyme. In the proposed reaction mechanism, the active-site cysteine residue of GSTO1-1 reacts with the S-(phenacyl)glutathione substrate to give an acetophenone and a mixed disulfide with the active-site cysteine; a second thiol substrate (e.g., glutathione or 2-mercaptoethanol) reacts with the active-site disulfide to regenerate the catalytically active enzyme and to form a mixed disulfide. A new spectrophotometric assay was developed that allows the rapid determination of SPG-R activity and specific measurement of GSTO1-1 in the presence of other GSTs. This is the first specific reaction attributed to GSTO1-1, and these results demonstrate the catalytic diversity of GSTO1-1, which, in addition to SPG-R activity, catalyzes the reduction of dehydroascorbate and monomethylarsonate(V) and also possesses thioltransferase and GST activity. PMID:17226937

  5. [Formulation and clinical test of a novel mucosal adhesive ointment].

    PubMed

    Bremecker, K D; Klein, G; Strempel, H; Rübesamen-Vokuhl, A

    1983-01-01

    A novel mucosal adhesive ointment on the base of partly neutralized polymethacrylic acid methyl ester (Eudispert) was formulated. The flow curves of the ointment show a pseudoplastic quality without any thixotropic effect. The viscosity depended on the kind and concentration of the base. During the clinical studies the pure ointment as well as a tretinoin-preparation for a lichen planus treatment showed no local irritation, good mucosal adhesion and suitable way of application for the patients. PMID:6683541

  6. 5 Morphology of the mucosal lesion in gluten sensitivity

    Microsoft Academic Search

    Michael N. Marsh; Peter T. Crowe

    1995-01-01

    Gluten sensitivity is associated with a spectrum of mucosal lesions, arbitrarily termed pre-infiltrative, infiltrative-hyperplastic, flat-destructive and atrophic-hypoplastic. Histologically and immunohistologically these lesions are all compatible with T-cell-driven events operative at a local mucosal level. They are classifiable either in terms of antibody titres (pre-infiltrative) (see Chapter 10) or by the characteristic disposition of IELs throughout the surface and crypt epithelium.

  7. Diallyl disulphide depletes glutathione in Candida albicans

    PubMed Central

    Lemar, Katey M.; Aon, Miguel A.; Cortassa, Sonia; O’Rourke, Brian; T. Müller, Carsten; Lloyd, David

    2008-01-01

    Using two-photon scanning laser microscopy, we investigated the effect of an Allium sativum (garlic) constituent, diallyl disulphide (DADS), on key physiological functions of the opportunistic pathogen Candida albicans. A short 30 min exposure to 0.5 mm DADS followed by removal induced 70% cell death (50% necrotic, 20% apoptotic) within 2 h, increasing to 75% after 4 h. The early intracellular events associated with DADS-induced cell death were monitored with two-photon fluorescence microscopy to track mitochondrial membrane potential (??m), reactive oxygen species (ROS) and NADH or reduced glutathione (GSH) under aerobic conditions. DADS treatment decreased intracellular GSH and elevated intracellular ROS levels. Additionally, DADS induced a marked decrease of ??m and lowered respiration in cell suspensions and isolated mitochondria. In vitro kinetic experiments in cell-free extracts suggest that glutathione-S-transferase (GST) is one of the intracellular targets of DADS. Additional targets were also identified, including inhibition of a site or sites between complexes II-IV in the electron transport chain, as well as the mitochondrial ATP-synthase. The results indicate that DADS is an effective antifungal agent able to trigger cell death in Candida, most probably by eliciting oxidative stress as a consequence of thiol depletion and impaired mitochondrial function. PMID:17534841

  8. Mathematical modeling of the effects of glutathione on arsenic methylation

    PubMed Central

    2014-01-01

    Background Arsenic is a major environmental toxin that is detoxified in the liver by biochemical mechanisms that are still under study. In the traditional metabolic pathway, arsenic undergoes two methylation reactions, each followed by a reduction, after which it is exported and released in the urine. Recent experiments show that glutathione plays an important role in arsenic detoxification and an alternative biochemical pathway has been proposed in which arsenic is first conjugated by glutathione after which the conjugates are methylated. In addition, in rats arsenic-glutathione conjugates can be exported into the plasma and removed by the liver in the bile. Methods We have developed a mathematical model for arsenic biochemistry that includes three mechanisms by which glutathione affects arsenic methylation: glutathione increases the speed of the reduction steps; glutathione affects the activity of arsenic methyltranferase; glutathione sequesters inorganic arsenic and its methylated downstream products. The model is based as much as possible on the known biochemistry of arsenic methylation derived from cellular and experimental studies. Results We show that the model predicts and helps explain recent experimental data on the effects of glutathione on arsenic methylation. We explain why the experimental data imply that monomethyl arsonic acid inhibits the second methylation step. The model predicts time course data from recent experimental studies. We explain why increasing glutathione when it is low increases arsenic methylation and that at very high concentrations increasing glutathione decreases methylation. We explain why the possible temporal variation of the glutathione concentration affects the interpretation of experimental studies that last hours. Conclusions The mathematical model aids in the interpretation of data from recent experimental studies and shows that the Challenger pathway of arsenic methylation, supplemented by the glutathione effects described above, is sufficient to understand and predict recent experimental data. More experimental studies are needed to explicate the detailed mechanisms of action of glutathione on arsenic methylation. Recent experimental work on the effects of glutathione on arsenic methylation and our modeling study suggest that supplements that increase hepatic glutathione production should be considered as strategies to reduce adverse health effects in affected populations. PMID:24885596

  9. Oral mucositis in children suffering from acute lymphoblastic leukaemia

    PubMed Central

    2012-01-01

    Aim of the study Oral mucositis is the most commonly reported side effect observed in neoplastic patients treated with chemotherapy and radiotherapy of the head and neck region as well as in patients who have received a haematopoietic stem cell transplant. The aim of the study was to assess the oral mucosa status in children with acute lymphoblastic leukaemia (ALL) during antineoplastic therapy. Material and methods The clinical examination included 78 children aged 2-18 with ALL. The clinical examination was conducted using the dental preset tray. The condition of the oral mucosa was determined using the WHO scale for oral mucositis. Results In the first period of antineoplastic therapy the pathological lesions of the oral mucosa of the mucositis type were observed among the examined patients. The lesions had various levels of intensity. Pain was found to be the primary symptom of oral mucositis. In this study the following were observed: local erythema of the oral mucosa in 35%, white pseudomembranous lesions in 18%, erosions in 40% and oral ulcerative lesions in 4% of patients who underwent the antineoplastic therapy. Oral mucositis was observed in 3.17% of children after 6 months of chemotherapy. Conclusion Local treatment of oral mucositis with polyantibiotic-antifungal mixture, supporting antifungal systemic treatment, and improving the overall peripheral blood conditions in children suffering from acute lymphoblastic leukaemia improve the condition of the oral mucosa. PMID:23788849

  10. 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.

  11. Differential expression of HIF-1? in skin and mucosal wounds.

    PubMed

    Chen, L; Gajendrareddy, P K; DiPietro, L A

    2012-09-01

    Despite accelerated epithelial closure, oral mucosal wounds exhibit lower levels of VEGF and a more refined angiogenic response than do skin wounds. The specific differences in angiogenesis suggest that skin and oral mucosal wounds may experience dissimilar levels of hypoxia and HIF-1?. Using a model of comparable wounds on murine dorsal skin and tongue, we determined levels of hypoxia and HIF-1?. Skin wounds were found to be significantly more hypoxic and had higher levels of HIF-1? than mucosal wounds. Furthermore, under stressed conditions, skin wounds, but not mucosal wounds, exhibited a further elevation of HIF-1? beyond that of non-stressed levels. To determine if manipulation of oxygen levels might equalize the repair response of each tissue, we exposed mice to hyperbaric oxygen treatment (HBOT) following wounding. HBOT did not significantly change HIF-1? or VEGF expression in either skin or mucosal wounds, nor did it alter wound bed vascularity. These studies suggest that skin wounds have higher levels of hypoxia than do mucosal wounds, along with a differential expression of HIF-1?. Interestingly, modulation of oxygen by HBOT does not ameliorate this difference. These results suggest that differential responses to hypoxia may underlie the distinctive wound-healing phenotypes seen in skin and oral mucosa. PMID:22821237

  12. Differential Expression of HIF-1? in Skin and Mucosal Wounds

    PubMed Central

    Chen, L.; Gajendrareddy, P.K.; DiPietro, L.A.

    2012-01-01

    Despite accelerated epithelial closure, oral mucosal wounds exhibit lower levels of VEGF and a more refined angiogenic response than do skin wounds. The specific differences in angiogenesis suggest that skin and oral mucosal wounds may experience dissimilar levels of hypoxia and HIF-1?. Using a model of comparable wounds on murine dorsal skin and tongue, we determined levels of hypoxia and HIF-1?. Skin wounds were found to be significantly more hypoxic and had higher levels of HIF-1? than mucosal wounds. Furthermore, under stressed conditions, skin wounds, but not mucosal wounds, exhibited a further elevation of HIF-1? beyond that of non-stressed levels. To determine if manipulation of oxygen levels might equalize the repair response of each tissue, we exposed mice to hyperbaric oxygen treatment (HBOT) following wounding. HBOT did not significantly change HIF-1? or VEGF expression in either skin or mucosal wounds, nor did it alter wound bed vascularity. These studies suggest that skin wounds have higher levels of hypoxia than do mucosal wounds, along with a differential expression of HIF-1?. Interestingly, modulation of oxygen by HBOT does not ameliorate this difference. These results suggest that differential responses to hypoxia may underlie the distinctive wound-healing phenotypes seen in skin and oral mucosa. PMID:22821237

  13. Effects of infrasound on gastric mucosal blood flow in rats.

    PubMed

    Morioka, I; Kuriyama, Y; Miyashita, K; Takeda, S

    1996-07-01

    To clarify the effects of infrasound on gastric mucosal blood flow, rats were exposed to infrasound for 20 minutes. The sounds were pure tones of 8, 16 and 32 Hz, at sound levels ranging from 80 dB to 130 dB. Gastric mucosal blood flow was determined by the inhaled hydrogen gas clearance method. Norepinephrine and epinephrine concentrations in the plasma were also measured. The exposed rats showed decreased gastric mucosal blood flow with increasing sound levels of infrasound at each octave-band frequency. To significantly decrease the gastric mucosal blood flow, infrasound at 32, 16 and 8 Hz needed sound levels of 100, 110 and 130 dB, respectively. These findings suggest that, as the frequency of infrasound decreases, an increased sound level is necessary to decrease the gastric mucosal blood flow. The norepinephrine and epinephrine concentrations in the plasma were 0.65±0.47n.g/ml and 0.35±0.43 ng/ml, respectively, in the control rats, while the corresponding values were 0.91±0.87 ng/ml and 0.74±0.81 ng/ml, respectively, in the exposed rats. There were significant increases (p>0.05) in norepinephrine and epinephrine. Thus, it is probable that exposure to infrasound stimulates the sympathetic nervous system and causes a decrease in gastric mucosal blood flow. PMID:21432425

  14. Mucosal effects of tenofovir 1% gel

    PubMed Central

    Hladik, Florian; Burgener, Adam; Ballweber, Lamar; Gottardo, Raphael; Vojtech, Lucia; Fourati, Slim; Dai, James Y; Cameron, Mark J; Strobl, Johanna; Hughes, Sean M; Hoesley, Craig; Andrew, Philip; Johnson, Sherri; Piper, Jeanna; Friend, David R; Ball, T Blake; Cranston, Ross D; Mayer, Kenneth H; McElrath, M Juliana; McGowan, Ian

    2015-01-01

    Tenofovir gel is being evaluated for vaginal and rectal pre-exposure prophylaxis against HIV transmission. Because this is a new prevention strategy, we broadly assessed its effects on the mucosa. In MTN-007, a phase-1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies (15 subjects/arm). We also treated primary vaginal epithelial cells from four healthy women with tenofovir in vitro. After seven days of administration, tenofovir 1% gel had broad-ranging effects on the rectal mucosa, which were more pronounced than, but different from, those of the detergent nonoxynol-9. Tenofovir suppressed anti-inflammatory mediators, increased T cell densities, caused mitochondrial dysfunction, altered regulatory pathways of cell differentiation and survival, and stimulated epithelial cell proliferation. The breadth of mucosal changes induced by tenofovir indicates that its safety over longer-term topical use should be carefully monitored. DOI: http://dx.doi.org/10.7554/eLife.04525.001 PMID:25647729

  15. Clotrimazole nanoparticle gel for mucosal administration.

    PubMed

    Esposito, Elisabetta; Ravani, Laura; Contado, Catia; Costenaro, Andrea; Drechsler, Markus; Rossi, Damiano; Menegatti, Enea; Grandini, Alessandro; Cortesi, Rita

    2013-01-01

    In this study a formulation suitable to be applied on oral and/or vaginal mucosa has been developed for the treatment of fungal infections. The aim of the research is a comparison between clotrimazole (CLO) containing semisolid formulations based on monoolein aqueous dispersion (MAD) or nanostructured lipid carrier (NLC). MAD and NLC have been characterized in terms of morphology and dimensional distribution by cryogenic Transmission Electron Microscopy (cryo-TEM) and Photon Correlation Spectroscopy (PCS). CLO was encapsulated with high entrapment efficiency both in MAD and in NLC, according to Sedimentation Field Flow Fractionation (SdFFF) combined with HPLC. CLO recovery in MAD and NLC has been investigated by time. In order to obtain formulations with suitable viscosity for mucosal application, MAD was diluted with a carbomer gel, while NLC was directly viscosized by the addition of poloxamer 407 in the dispersion. The rheological properties of MAD and NLC after viscosizing have been investigated. Franz cell has been employed to study CLO diffusion from the different vehicles, evidencing diffusion rates from MAD and NLC superimposable to that obtained using Canesten(®). An anticandidal activity study demonstrated that both CLO-MAD and CLO-NLC were more active against Candida albicans with respect to the pure drug. PMID:25428089

  16. Mucosal immune responses following intestinal nematode infection.

    PubMed

    Zaph, C; Cooper, P J; Harris, N L

    2014-09-01

    In most natural environments, the large majority of mammals harbour parasitic helminths that often live as adults within the intestine for prolonged periods (1-2 years). Although these organisms have been eradicated to a large extent within westernized human populations, those living within rural areas of developing countries continue to suffer from high infection rates. Indeed, recent estimates indicate that approximately 2.5 billion people worldwide, mainly children, currently suffer from infection with intestinal helminths (also known as geohelminths and soil-transmitted helminths) . Paradoxically, the eradication of helminths is thought to contribute to the increased incidence of autoimmune diseases and allergy observed in developed countries. In this review, we will summarize our current understanding of host-helminth interactions at the mucosal surface that result in parasite expulsion or permit the establishment of chronic infections with luminal dwelling adult worms. We will also provide insight into the adaptive immune mechanisms that provide immune protection against re-infection with helminth larvae, a process that is likely to be key to the future development of successful vaccination strategies. Lastly, the contribution of helminths to immune modulation and particularly to the treatment of allergy and inflammatory bowel disease will be discussed. PMID:25201407

  17. Mucosal effects of tenofovir 1% gel.

    PubMed

    Hladik, Florian; Burgener, Adam; Ballweber, Lamar; Gottardo, Raphael; Vojtech, Lucia; Fourati, Slim; Dai, James Y; Cameron, Mark J; Strobl, Johanna; Hughes, Sean M; Hoesley, Craig; Andrew, Philip; Johnson, Sherri; Piper, Jeanna; Friend, David R; Ball, T Blake; Cranston, Ross D; Mayer, Kenneth H; McElrath, M Juliana; McGowan, Ian

    2015-01-01

    Tenofovir gel is being evaluated for vaginal and rectal pre-exposure prophylaxis against HIV transmission. Because this is a new prevention strategy, we broadly assessed its effects on the mucosa. In MTN-007, a phase-1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies (15 subjects/arm). We also treated primary vaginal epithelial cells from four healthy women with tenofovir in vitro. After seven days of administration, tenofovir 1% gel had broad-ranging effects on the rectal mucosa, which were more pronounced than, but different from, those of the detergent nonoxynol-9. Tenofovir suppressed anti-inflammatory mediators, increased T cell densities, caused mitochondrial dysfunction, altered regulatory pathways of cell differentiation and survival, and stimulated epithelial cell proliferation. The breadth of mucosal changes induced by tenofovir indicates that its safety over longer-term topical use should be carefully monitored. PMID:25647729

  18. Dendritic Cells at the Oral Mucosal Interface

    PubMed Central

    Cutler, C.W.; Jotwani, R.

    2008-01-01

    The mucosal lining of the respiratory and digestive systems contains the largest and most complex immune system in the body, but surprisingly little is known of the immune system that serves the oral mucosa. This review focuses on dendritic cells, particularly powerful arbiters of immunity, in response to antigens of microbial or tumor origin, but also of tolerance to self-antigens and commensal microbes. Although first discovered in 1868, the epidermal dendritic Langerhans cells remained enigmatic for over a century, until they were identified as the most peripheral outpost of the immune system. Investigators’ ability to isolate, enrich, and culture dendritic cells has led to an explosion in the field. Presented herein is a review of dendritic cell history, ontogeny, function, and phenotype, and the role of different dendritic cell subsets in the oral mucosa and its diseases. Particular emphasis is placed on the mechanisms of recognition and capture of microbes by dendritic cells. Also emphasized is how dendritic cells may regulate immunity/tolerance in response to oral microbes. PMID:16861283

  19. Basics of GI Physiology and Mucosal Immunology

    Microsoft Academic Search

    Alessio Fasano; Terez Shea-Donohue

    \\u000a \\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a The intestine has the largest mucosal surface interfacing with external environment.\\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Tight junctions are pivotal in intestinal barrier function.\\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Gut associated lymphoid tissue (GALT) serves to prevent harmful antigens from reaching systemic circulation as well as inducing\\u000a immune tolerance.\\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Intestinal microbiota surpasses the human genome by 140-fold and is critical in the development of GALT.\\u000a \\u000a \\u000a \\u000a • 

  20. Influence of supplemental high molecular weight pullulan or ?-cyclodextrin on ileal and total tract nutrient digestibility, fecal characteristics, and microbial populations in the dog

    Microsoft Academic Search

    Julie K. Spears; Lisa K. Karr-Lilienthal; George C. Fahey Jr

    2005-01-01

    This study was conducted to determine if supplemental pullulan and ?-cyclodextrin affect canine nutrient digestibility, microbial populations, and fecal characteristics. Ileal cannulated dogs were fed a commercial diet, and treatments were administered daily in a 5×5 Latin square design: (i) no supplement; (ii) 2 g pullulan; (iii) 4 g pullulan; (iv) 2 g ?-cyclodextrin; (v) 4 g ?-cyclodextrin. Ileal and

  1. Proanthocyanidin from Grape Seed Extracts Protects Indomethacin-Induced Small Intestinal Mucosal Injury

    PubMed Central

    Cheung, Dae Young; Kim, Jin Il; Park, Soo-Heon; Kim, Jae Kwang

    2014-01-01

    Proanthocyanidin (grape seed proanthocyanidin extracts, GSPEs) is an antioxidant and scavenges free radicals. Excessive oxidative stress and free radical production are major components in the pathogenesis of NSAID-induced small intestinal injury. We investigated the effect of GSPEs on indomethacin-induced intestinal mucosal injury in the rat. Rats were allocated into four groups: the null control group, the indomethacin control group, the low-dose GSPEs group, and the high-dose GSPEs group. GSPEs were administered for 4 days. Then indomethacin and GSPEs were coadministered for the following 2 days by oral route. The dose of indomethacin was 200?mg/Kg. The doses of GSPEs were 100?mg/Kg for low-dose group and 300?mg/Kg for high-dose group. Luminal bleeding was solely observed in one of 5 rats from indomethacin control group. The number of ulcer count was reduced to 0.1 ± 0.3 per rat in GSPEs treated group compared to 1.4 ± 0.5 per rat in indomethacin control group. Submucosal inflammatory cell infiltration was also reduced to 50% in GSPEs treated group. The tissue level of prostaglandin E2 was not affected by GSPEs treatment. GSPEs attenuated the indomethacin-induced small intestinal injury irrespective of the tissue PGE2 depletion and glutathione consumption. PMID:24868202

  2. Standardized ileal amino acid digestibility in egg from hyperimmunized hens fed to weaned pigs.

    PubMed

    Heo, J M; Kiarie, E; Kahindi, R K; Maiti, P; Woyengo, T A; Nyachoti, C M

    2012-12-01

    The study was conducted to determine the apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of AA in egg from hens hyperimmunized with Escherichia coli K88 antigens (EGG) fed to weaned pigs. Spray dried porcine plasma (SDPP) was included for comparison. Eight barrows (Yorkshire-Landrace × Duroc; initial BW of 17 ± 1 kg) were fitted with a T-cannula at the distal ileum and fed 2 diets in a completely randomized design to give 4 replicates per diet. The diets were corn (Zea mays) starch based with either EGG or SDPP as the sole source of protein and were formulated to contain 130 g/kg CP. At the end of the study, a 50 g/kg casein diet was fed to all pigs (n = 8) to quantify endogenous N and AA losses to determine SID. Titanium dioxide (3 g/kg) was included in the diets as an indigestible maker. Each period lasted for 7 d. Pigs were adapted to their respective diets for 5 d followed by 12 h of continuous ileal digesta collection on days 6 and 7. Daily feed allowance was set at 4% BW at the beginning of each period and offered in 2 equal portions at 0800 and 1600 h as a dry mash. Pigs had unlimited access to water via low pressure nipple drinkers. The AID (%) of CP and indispensable AA were lower (P < 0.05) in EGG compared with SDPP. The SID (%) of CP (82 vs. 96) and indispensable AA were lower (P < 0.05) in pigs fed EGG compared with SDPP. In conclusion, the average AID and SID of N and indispensable AA in EGG are lower than in SDPP when fed at high levels. PMID:23365342

  3. Glutathione Redox System in ?-Thalassemia/Hb E Patients

    PubMed Central

    Tangjaidee, Thongchai; Hatairaktham, Suneerat; Charoensakdi, Ratiya; Panichkul, Narumol; Siritanaratkul, Noppadol; Fucharoen, Suthat

    2013-01-01

    ?-thalassemia/Hb E is known to cause oxidative stress induced by iron overload. The glutathione system is the major endogenous antioxidant that protects animal cells from oxidative damage. This study aimed to determine the effect of disease state and splenectomy on redox status expressed by whole blood glutathione (GSH)/glutathione disulfide (GSSG) and also to evaluate glutathione-related responses to oxidation in ?-thalassemia/Hb E patients. Twenty-seven normal subjects and 25 ?-thalassemia/Hb E patients were recruited and blood was collected. The GSH/GSSG ratio, activities of glutathione-related enzymes, hematological parameters, and serum ferritin levels were determined in individuals. Patients had high iron-induced oxidative stress, shown as significantly increased serum ferritin, a decreased GSH/GSSG ratio, and increased activities of glutathione-related enzymes. Splenectomy increased serum ferritin levels and decreased GSH levels concomitant with unchanged glutathione-related enzyme activities. The redox ratio had a positive correlation with hemoglobin levels and negative correlation with levels of serum ferritin. The glutathione system may be the body's first-line defense used against oxidative stress and to maintain redox homeostasis in thalassemic patients based on the significant correlations between the GSH/GSSH ratio and degree of anemia or body iron stores. PMID:24223032

  4. Non-linear stress-strain measurements of ex vivo produced oral mucosal equivalent (EVPOME) compared to normal oral mucosal and skin tissue

    Microsoft Academic Search

    Frank Winterroth; Scott J. Hollister; Stephen E. Feinberg; Shiuhyang Kuo; J. Brian Fowlkes; Arindam Ganguly; Kyle W. Hollman

    2011-01-01

    Stress-strain curves of oral mucosal tissues were measured using direct mechanical testing. Measurements were conducted on both natural oral mucosal tissues and engineered devices, specifically a clinically developed ex vivo produced oral mucosal equivalent (EVPOME). As seeded cells proliferate on EVPOME devices, they produce a keratinized protective upper layer which fills in surface irregularities. These transformations can further alter stress-strain

  5. Sickness Impact Profile (SIP) Score, a Good Alternative Instrument for Measuring Quality of Life in Patients with Ileal Urinary Diversions

    PubMed Central

    Prcic, Alden; Aganovic, Damir; Hadziosmanovic, Osman

    2013-01-01

    Objective: To determine the effectiveness of the use of the SIP score and the quality of life impairment in patients with ileal conduit and orthotropic ileal derivations by Hautmann and AbolEnein/Ghoneim. Methods: Prospectively evaluated 146 patients in different age groups. In 66 patients ileal conduit derivation was performed, in 20 patients orthotropic derivation using Hautman technique was recorded and in 20 of them AbolEnein/Ghoneim was used. Prior to examining patients with urinary diversions, 40 patients with minor urological symptoms not requiring any active treatment, were surveyed in order to validate SIP score. Six months after the operation, all patients with urinary diversions filled the SIP score questionnaire. Results: Using Crombach’s Alpha equation the high reliability of SIP questionnaire was proven. Average scale value was 0,93. Using descriptive statistics mean values of all categories and dimensions of the SIP questionnaire of examined patients were determined, calculated according to the questionnaire manual being converted to percentage. Total value of SIP score for the ileal conduit group was 34,76% and in orthotropic derivation 18,52% respectively. For Hautmann procedure total SIP score was 18,35% and for AbolEnein/Ghoneim 18,7%. In the control group total SIP score was 9%. The most influential dimensions on the total score of ileal conduit were physical and psycho-social, while independent dimension did not significantly influent total SIP score. Conclusion: Taking into consideration the lack of questionnaires on quality of life for urinary derivations, SIP score as a general disease influence to the quality of life questionnaire represents a reliable alternative for objectification and quantification of the quality of life upon urinary derivation. According to this instrument, orthotropic derivations provide significantly better quality of life compared to ileal conduit. PMID:24167383

  6. Laparoscopic diverted resleeve with ileal transposition for failed laparoscopic sleeve gastrectomy: a case report.

    PubMed

    Çelik, Alper; Ugale, Surendra; Ofluo?lu, Hasan

    2015-01-01

    Laparoscopic sleeve gastrectomy (LSG) recently gained popularity for the treatment of obesity and related co-morbidities. With the increasing number of bariatric operations, the requirement for redo or revision bariatric surgery seems to be increasing. In the present case, a 50-year-old female patient with failed LSG who underwent laparoscopic resleeve, duodenal diversion, and ileal transposition is presented. Her metabolic and biochemical parameters were found to be improved significantly after 18 months. To the best of our knowledge, this is the first report of a case treated with this method in the literature. PMID:25578286

  7. Esophageal atresia, small omphalocele and ileal prolapse through a patent omphalomesenteric duct: a methamizole embryopathy?

    PubMed

    Panait, Nicoleta; Michel, Fabrice; D'Ercole, Claude; Merrot, Thierry

    2013-06-01

    Newborns prenatally exposed to methimazole (active metabolite of carbamizole) for maternal hyperthyroidism may present some disorders in common, but the phenotype is not well defined. Choanal atresia is the most frequent, and other anomalies such as esophageal atresia and aplasia cutis were described with this embryopathy. Additionally, patent omphalomesenteric duct or Meckel's diverticulum in similar association was reported in some patients. The predisposed genetic background has to be considered. We report the case of a newborn exposed to carbamizole during the first 4 weeks of pregnancy and define an association related to prenatal methamizole exposure consisting of esophageal atresia, small omphalocele, and ileal prolapse through a patent omphalomesenteric duct. PMID:23845657

  8. Gene Gun-Mediated DNA Immunization Primes Development of Mucosal Immunity against Bovine Herpesvirus 1 in Cattle

    Microsoft Academic Search

    B. I. Loehr; P. Willson; L. A. Babiuk; S. van Drunen Littel-van den Hurk

    2000-01-01

    Vaccination by a mucosal route is an excellent approach to the control of mucosally acquired infections. Several reports on rodents suggest that DNA vaccines can be used to achieve mucosal immunity when applied to mucosal tissues. However, with the exception of one study with pigs and another with horses, there is no in- formation on mucosal DNA immunization of the

  9. Clinicopathological evaluation of anoxic mucosal injury in strangulation ileus

    PubMed Central

    2014-01-01

    Background In patients with strangulation ileus, the severity of bowel ischemia is unpredictable before surgery. To consider a grading scale of anoxic damage, we evaluated the pathological findings and investigated predictive factors for bowel gangrene. Methods We assessed 49 patients with strangulation ileus who underwent a laparotomy between January 2004 and November 2012. Laboratory tests and the contrast computed tomography (CT) were evaluated before surgery. According to the degree of mucosal degeneration, we classified anoxic damages into the following 3 grades. Ggrade 1 shows mild mucosal degeneration with extended subepithelial space. Grade 2 shows moderate degeneration and mucosal deciduation with residual mucosa on the muscularis mucosae. Grade 3 shows severe degeneration and mucosal digestion with disintegration of lamina propria. Results Resected bowel specimens were obtained from the 36 patients with severe ischemia, while the remaining 13 patients avoided bowel resection. The mucosal injury showed grade 1 in 11 cases, grade 2 in 10 cases, and grade 3 in 15 cases. The patients were divided into two groups. One group included grade 1 and non-resected patients (n?=?24) while the other included grades 2 and 3 (n?=?25). When comparing the clinical findings for these groups, elevated creatine kinase (P?=?0.017), a low base excess (P?=?0.021), and decreased bowel enhancement on the contrast CT (P?=?0.001) were associated with severe mucosal injury. Conclusion In strangulation ileus, anoxic mucosal injury progresses gradually after rapid spreading of bowel congestion. Before surgical intervention, creatine kinase, base excess, and bowel enhancement on the contrast CT could indicate the severity of anoxic damage. These biomarkers could be the predictor for bowel resection before surgery. PMID:25319494

  10. Mucosal immunoglobulins and B cells of Teleost fish

    PubMed Central

    Salinas, Irene; Zhang, Yong-An; Sunyer, J. Oriol

    2012-01-01

    As physical barriers that separate teleost fish from the external environment, mucosae are also active immunological sites that protect them against exposure to microbes and stressors. In mammals, the sites where antigens are sampled from mucosal surfaces and where stimulation of naive T and B lymphocytes occurs are known as inductive sites and are constituted by mucosa-associated lymphoid tissue (MALT). According to anatomical location, the MALT in teleost fish is subdivided into gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), and gill-associated lymphoid tissue (GIALT). All MALT contain a variety of leukocytes, including, but not limited to, T cells, B cells, plasma cells, macrophages and granulocytes. Secretory immunoglobulins are produced mainly by plasmablasts and plasma cells, and play key roles in the maintenance of mucosal homeostasis. Until recently, teleost fish B cells were thought to express only two classes of immunoglobulins, IgM and IgD, in which IgM was thought to be the only one responding to pathogens both in systemic and mucosal compartments. However, a third teleost immunoglobulin class, IgT/IgZ, was discovered in 2005, and it has recently been shown to behave as the prevalent immunoglobulin in gut mucosal immune responses. The purpose of this review is to summarise the current knowledge of mucosal immunoglobulins and B cells of fish MALT. Moreover, we attempt to integrate the existing knowledge on both basic and applied research findings on fish mucosal immune responses, with the goal to provide new directions that may facilitate the development of novel vaccination strategies that stimulate not only systemic, but also mucosal immunity. PMID:22133710

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  12. ABIOTIC STRESS ALTERS TRANSCRIPT PROFILES AND ACTIVITY OF GLUTATHIONE S-TRANSFERASE, GLUTHIONE PEROXIDASE, AND GLUTATHIONE REDUCTASE IN EUPHORBIA ESULA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leafy spurge (Euphorbia esula L.) is an invasive perennial weed in North American plains and prairies which exhibits remarkable tolerance towards abiotic and biotic stress. Glutathione plays an important role in plant defense mechanisms and varying degrees of glutathione S-transferase (GST), glutat...

  13. Glutathione S-transferase in human organs.

    PubMed

    Sherman, M; Titmuss, S; Kirsch, R E

    1983-01-01

    Glutathione S-transferase (GSH-T) distribution has been investigated in human tissues. The relative contribution of each species to total enzyme activity of the various tissues has been compared. "Cationic" (pI greater than 7.5) "neutral" (pI 6-6.5) and "anionic" (pI less than 5.4) species of GSH-T were separated by isoelectric focusing. "Cationic" GSH-Ts (ligandin) quantitated by radioimmunoassay were present in all tissues studied. Highest concentrations were in liver, kidney, duodenum, testis and adrenal. "Neutral" and "anionic" GSH-Ts were not present in every tissue or in every specimen of some tissues studied. Marked inter-organ and inter-individual variation in the relative concentration of the 3 GSH-T species may explain individual and organ susceptibility to drugs and toxins and underlines the need for future studies to examine individual enzymes rather than total activity. PMID:6679314

  14. Glutathione-Dependent Detoxification Processes in Astrocytes.

    PubMed

    Dringen, Ralf; Brandmann, Maria; Hohnholt, Michaela C; Blumrich, Eva-Maria

    2014-11-27

    Astrocytes have a pivotal role in brain as partners of neurons in homeostatic and metabolic processes. Astrocytes also protect other types of brain cells against the toxicity of reactive oxygen species and are considered as first line of defence against the toxic potential of xenobiotics. A key component in many of the astrocytic detoxification processes is the tripeptide glutathione (GSH) which serves as electron donor in the GSH peroxidase-catalyzed reduction of peroxides. In addition, GSH is substrate in the detoxification of xenobiotics and endogenous compounds by GSH-S-transferases which generate GSH conjugates that are efficiently exported from the cells by multidrug resistance proteins. Moreover, GSH reacts with the reactive endogenous carbonyls methylglyoxal and formaldehyde to intermediates which are substrates of detoxifying enzymes. In this article we will review the current knowledge on the GSH metabolism of astrocytes with a special emphasis on GSH-dependent detoxification processes. PMID:25428182

  15. Targeting maladaptive glutathione responses in lung disease

    PubMed Central

    Gould, Neal S.; Day, Brian J

    2010-01-01

    The lung is unique being exposed directly to the atmospheric environment containing xenobiotics, pathogens, and other agents which are continuously inhaled on a daily basis. Additionally, the lung is exposed to higher ambient oxygen levels which can promote the formation of a complex number of reactive oxygen and nitrogen species. Due to this constant barrage of potential damaging agents, the lung has developed a high degree of plasticity in dealing with ever changing conditions. In the present commentary, we will focus on glutathione (GSH) as a key antioxidant in the lung airways and discuss mechanisms by which the lung uses GSH to adapt to its rapidly changing environment. We will then examine the evidence on how defective and inadequate adaptive responses can lead to lung injury, inflammation and disease. Lastly, we will examine some of the recent attempts to alter lung GSH levels with therapies in a number of human lung diseases and discuss some of the limitations of such approaches. PMID:20951119

  16. Efficient nitrosation of glutathione by nitric oxide?

    PubMed Central

    Kolesnik, Bernd; Palten, Knut; Schrammel, Astrid; Stessel, Heike; Schmidt, Kurt; Mayer, Bernd; Gorren, Antonius C.F.

    2013-01-01

    Nitrosothiols are increasingly regarded as important participants in a range of physiological processes, yet little is known about their biological generation. Nitrosothiols can be formed from the corresponding thiols by nitric oxide in a reaction that requires the presence of oxygen and is mediated by reactive intermediates (NO2 or N2O3) formed in the course of NO autoxidation. Because the autoxidation of NO is second order in NO, it is extremely slow at submicromolar NO concentrations, casting doubt on its physiological relevance. In this paper we present evidence that at submicromolar NO concentrations the aerobic nitrosation of glutathione does not involve NO autoxidation but a reaction that is first order in NO. We show that this reaction produces nitrosoglutathione efficiently in a reaction that is strongly stimulated by physiological concentrations of Mg2+. These observations suggest that direct aerobic nitrosation may represent a physiologically relevant pathway of nitrosothiol formation. PMID:23660531

  17. Nomenclature for mammalian soluble glutathione transferases.

    PubMed

    Mannervik, Bengt; Board, Philip G; Hayes, John D; Listowsky, Irving; Pearson, William R

    2005-01-01

    The nomenclature for human soluble glutathione transferases (GSTs) is extended to include new members of the GST superfamily that have been discovered, sequenced, and shown to be expressed. The GST nomenclature is based on primary structure similarities and the division of GSTs into classes of more closely related sequences. The classes are designated by the names of the Greek letters: Alpha, Mu, Pi, etc., abbreviated in Roman capitals: A, M, P, and so on. (The Greek characters should not be used.) Class members are distinguished by Arabic numerals and the native dimeric protein structures are named according to their subunit composition (e.g., GST A1-2 is the enzyme composed of subunits 1 and 2 in the Alpha class). Soluble GSTs from other mammalian species can be classified in the same manner as the human enzymes, and this chapter presents the application of the nomenclature to the rat and mouse GSTs. PMID:16399376

  18. Glutathione transferases in the bioactivation of azathioprine.

    PubMed

    Modén, Olof; Mannervik, Bengt

    2014-01-01

    The prodrug azathioprine is primarily used for maintaining remission in inflammatory bowel disease, but approximately 30% of the patients suffer adverse side effects. The prodrug is activated by glutathione conjugation and release of 6-mercaptopurine, a reaction most efficiently catalyzed by glutathione transferase (GST) A2-2. Among five genotypes of GST A2-2, the variant A2*E has threefold-fourfold higher catalytic efficiency with azathioprine, suggesting that the expression of A2*E could boost 6-mercaptopurine release and adverse side effects in treated patients. Structure-activity studies of the GST A2-2 variants and homologous alpha class GSTs were made to delineate the determinants of high catalytic efficiency compared to other alpha class GSTs. Engineered chimeras identified GST peptide segments of importance, and replacing the corresponding regions in low-activity GSTs by these short segments produced chimeras with higher azathioprine activity. By contrast, H-site mutagenesis led to decreased azathioprine activity when active-site positions 208 and 213 in these favored segments were mutagenized. Alternative substitutions indicated that hydrophobic residues were favored. A pertinent question is whether variant A2*E represents the highest azathioprine activity achievable within the GST structural framework. This issue was addressed by mutagenesis of H-site residues assumed to interact with the substrate based on molecular modeling. The mutants with notably enhanced activities had small or polar residues in the mutated positions. The most active mutant L107G/L108D/F222H displayed a 70-fold enhanced catalytic efficiency with azathioprine. The determination of its structure by X-ray crystallography showed an expanded H-site, suggesting improved accommodation of the transition state for catalysis. PMID:24974183

  19. COMPARISON OF PLASMA MALONDIALDEHYDE, GLUTATHIONE, GLUTATHIONE PEROXIDASE, HYDROXYPROLINE AND SELENIUM LEVELS IN PATIENTS WITH VITILIGO AND HEALTHY CONTROLS

    PubMed Central

    Ozturk, I. Cetin; Batcioglu, Kadir; Karatas, Fikret; Hazneci, Ersoy; Genc, Metin

    2008-01-01

    Background: The etiology and pathophysiologic mechanism of vitiligo are still unclear. The relationship between increased oxidative stress due to the accumulation of radicals and reactive oxygen species and the associated changes in blood and epidermal component of vitiliginous skin have been reported many times. We investigated the possible changes of plasma malondialdehyde, glutathione, selenium, hydroxyproline and glutathione peroxidase activity levels in patients with vitiligo in order to evaluate the relationship between oxidative stress and etiopathogenesis of vitiligo. Materials and Methods: Plasma malondialdehyde, glutathione, hydroxyproline and glutathione peroxidase activity levels were measured by spectrophotometric methods, and HPLC was used for measurement of selenium concentrations. Results: Our results showed increased malondialdehyde, hydroxyproline and glutathione peroxidase activity levels in plasma of vitiligo group (P < 0.05). Conclusion: Support of antioxidant system via nonenzymatic antioxidant compounds and antioxidant enzymes may be useful to prevent of melanocyte degeneration which occur due to oxidative damage in vitiligo. PMID:19882005

  20. 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. PMID:12806164

  1. The interaction of chromium (VI) with macrophages: depletion of glutathione and inhibition of glutathione reductase.

    PubMed

    Lalaouni, A; Henderson, C; Kupper, C; Grant, M H

    2007-07-01

    There are reports of alterations in the number and functions of the cells of the immune system in patients with metal-on-metal (MOM) orthopaedic implants. These effects have been correlated with elevated chromium levels in the patients' blood. We have investigated the interactions of clinically relevant concentrations of Cr VI with macrophages in vitro, and the mechanisms responsible for its toxicity. Cr VI causes a concentration dependent decrease in macrophage viability above 1 microM as measured by the MTT and Neutral Red assays. This falls well within the range of circulating chromium serum concentrations measured in patients with MOM. Intracellular reduced glutathione (GSH) levels fall as a result, and most of the loss (86%) is accounted for by oxidation to the dimer, GSSG. Prior depletion of GSH does not sensitise the cells to Cr VI toxicity, implying that it is not involved in protecting the cells against the effects of Cr VI. During the metabolism of Cr VI, glutathione reductase activity is inhibited. In contrast, the activities of catalase and superoxide dismutase are not significantly altered. Prior inhibition of glutathione reductase activity protects against the toxicity of Cr VI to a significant extent, suggesting that it reduces Cr VI to a toxic metabolite. PMID:17498860

  2. Effect of soybean meal origin on standardized ileal amino acid digestibility in piglets.

    PubMed

    Eklund, M; Sauer, N; Rink, F; Rademacher, M; Mosenthin, R

    2012-12-01

    The present study with piglets was conducted to estimate standardized ileal digestibility (SID) of AA in European Union soybean (Glycine max) meal (SBM) imports sourced from Argentina, Brazil, and the United States. Twelve piglets with an average initial BW of 9 kg (47 d of age) were fitted with a simple ileal T-cannula to determine SID of AA in 4 batches of SBM originating either from Argentina (n = 1), Brazil (n = 1), or the United States (n = 2; US1 and US2). A semisynthetic diet based on corn (Zea mays) starch and casein (125 g casein/kg as-fed) was supplemented with 1 of 4 batches SBM at an inclusion rate of 235 g SBM/kg (as-fed) each. The chemical composition did not differ largely, with CP contents ranging from 458 in Argentinean to 461 g/kg (as-fed) in US1 SBM. The SID of indispensable AA ranged from 80% in US2 SBM to 83% in Argentinean SBM and from 74% for Trp in US2 and Brazilian SBM to 91% for Arg in US2, Brazilian, and Argentinean SBM. Most SID values did not differ among the SBM batches (P > 0.05). In conclusion, European SBM imports from Brazil, Argentina, or the United Sates were similar in their chemical composition. For most AA, high and uniform SID values were obtained independent from their source of origin. PMID:23365325

  3. Prevention and Treatment of Oral Mucositis in Children with Cancer

    PubMed Central

    Miller, Misty M.; Donald, David V.; Hagemann, Tracy M.

    2012-01-01

    Oral mucositis affects more than three-fourths of patients undergoing chemotherapy and represents a significant burden to patients and caregivers. Lesions develop as a result of chemotherapeutic agents attacking the rapidly dividing cells of the gastrointestinal tract. Severity can range from mild, painless tissue changes to bleeding ulcerations that prevent oral intake and require narcotic pain relievers. Oral mucositis also leads to an increased risk of infection and can often delay further chemotherapy treatment. A number of assessment scales have been developed to better qualify the symptoms associated with this condition. Few pharmacologic agents have been approved to either prevent the development or alleviate the symptoms of oral mucositis. Current options include the use of antimicrobial mouthwashes, amino acid rinses, and topical healing agents. Palifermin, a keratinocyte growth factor, may be a future option after its use in children is explored. With achievements in other areas of supportive care in patients undergoing chemotherapy, oral mucositis should represent the forefront of new research. This review will provide a comprehensive examination of available options for children who have oral mucositis. PMID:23413048

  4. Glutathione activates virulence gene expression of an intracellular pathogen.

    PubMed

    Reniere, Michelle L; Whiteley, Aaron T; Hamilton, Keri L; John, Sonya M; Lauer, Peter; Brennan, Richard G; Portnoy, Daniel A

    2015-01-01

    Intracellular pathogens are responsible for much of the world-wide morbidity and mortality due to infectious diseases. To colonize their hosts successfully, pathogens must sense their environment and regulate virulence gene expression appropriately. Accordingly, on entry into mammalian cells, the facultative intracellular bacterial pathogen Listeria monocytogenes remodels its transcriptional program by activating the master virulence regulator PrfA. Here we show that bacterial and host-derived glutathione are required to activate PrfA. In this study a genetic selection led to the identification of a bacterial mutant in glutathione synthase that exhibited reduced virulence gene expression and was attenuated 150-fold in mice. Genome sequencing of suppressor mutants that arose spontaneously in vivo revealed a single nucleotide change in prfA that locks the protein in the active conformation (PrfA*) and completely bypassed the requirement for glutathione during infection. Biochemical and genetic studies support a model in which glutathione-dependent PrfA activation is mediated by allosteric binding of glutathione to PrfA. Whereas glutathione and other low-molecular-weight thiols have important roles in redox homeostasis in all forms of life, here we demonstrate that glutathione represents a critical signalling molecule that activates the virulence of an intracellular pathogen. PMID:25567281

  5. Role of Glutathione in protection against mercury induced poisoning.

    PubMed

    Khan, Haroon; Khan, Muhammad Farid; Jan, Syed Umer; Mukhtiar, Muhammad; Ullah, Naseem; Anwar, Naveed

    2012-04-01

    Mercury is harmless in an insoluble form, such as mercuric sulfide, but it is poisonous in soluble forms such as mercuric chloride or methylmercury. Mercury is a neurotoxin. Outbreaks of mercuric chloride poisonings have made it clear that adults, children, and developing fetuses are at risk from ingestion exposure to mercury. It is very important and interesting to study the reaction of mercuric chloride and Glutathione as biomarker of Glutathione role in detoxification and conjugation in components (Plasma and Cytosolic Fraction). The effect of mercuric chloride's different concentrations was examined on GSH present in plasma and cytosolic fraction. Decrease in GSH level was dependant on mercuric chloride concentration. The decrease in GSH level of blood components was more prominent with the time of incubation of mercuric chloride. Decrease in the concentration of reduced state Glutathione may be due the interaction of reduced state Glutathione (GSH) and mercuric chloride to form oxidized Glutathione (GSSG) or mercuric-glutathione complex. This change in GSH metabolic status provides information regarding the role of GSH in detoxification of mercuric chloride. The effect of mercury metal on Glutathione in blood components has been discussed in this paper in vitro condition as a model for in Vivo condition. PMID:22459468

  6. Fluorescein-labeled glutathione to study protein S-glutathionylation.

    PubMed

    Landino, Lisa M; Brown, Carolyn M; Edson, Carolyn A; Gilbert, Laura J; Grega-Larson, Nathan; Wirth, Anna Jean; Lane, Kelly C

    2010-07-01

    Numerous studies of S-glutathionylation of cysteine thiols indicate that this protein modification plays a key role in redox regulation of proteins. To facilitate the study of protein S-glutathionylation, we developed a synthesis and purification to produce milligram quantities of fluorescein-labeled glutathione. The amino terminus of the glutathione tripeptide reacted with fluorescein isothiocyanate readily in ammonium bicarbonate. Purification by solid phase extraction on C8 and C18 columns separated excess reactants from desired products. Both oxidized and reduced fluorescein-labeled glutathione reacted with a variety of thiol-containing proteins to yield fluorescent proteins. PMID:20156418

  7. How can probiotics and prebiotics impact mucosal immunity?

    PubMed Central

    Pot, Bruno

    2010-01-01

    The study of probiotics and prebiotics is an expanding field of interest and scientific research that has resulted in insights related to the host immune response. Recent advances have naturally led to key questions. What are the specific probiotic components that mediate immunomodulation? Can we extrapolate the results of in vitro studies in animal and human trials? Which biomarkers and immune parameters should be measured in probiotic and prebiotic intervention studies? These questions were part of a discussion entitled “How Can Probiotics and Prebiotics Impact Mucosal Immunity” at the 2009 Annual Meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP). This review highlights recent knowledge about the modulation of mucosal immunity by probiotics and prebiotics, as well as considerations for measuring their effects on mucosal immunity. A list of biomarkers and immune parameters to be measured in human clinical trials is included. PMID:21327037

  8. Border maneuvers: deployment of mucosal immune defenses against Toxoplasma gondii.

    PubMed

    Cohen, S B; Denkers, E Y

    2014-07-01

    Toxoplasma gondii is a highly prevalent protozoan pathogen that is transmitted through oral ingestion of infectious cysts. As such, mucosal immune defenses in the intestine constitute the first and arguably most important line of resistance against the parasite. The response to infection is now understood to involve complex three-way interactions between Toxoplasma, the mucosal immune system, and the host intestinal microbiota. Productive outcome of these interactions ensures resolution of infection in the intestinal mucosa. Nonsuccessful outcome may result in emergence of proinflammatory damage that can spell death for the host. Here, we discuss new advances in our understanding of the mechanisms underpinning these disparate outcomes, with particular reference to initiators, effectors, and regulators of mucosal immunity stimulated by Toxoplasma in the intestine. PMID:24717355

  9. Development of a precision-fed ileal amino acid digestibility assay using 3-week-old broiler chicks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of these studies was to develop a precision-fed ileal digestibility assay, primarily for amino acids (AA), using 3-wk-old broiler chicks. For all experiments, day-old Ross × Ross 708 broiler chicks were fed a standard corn-soybean meal starter diet until 21 d of age. In experiment 1, f...

  10. Effect of xylanase on apparent ileal and total tract digestibility of nutrients and energy of rye in young pigs

    Microsoft Academic Search

    So?a Nitrayová; Jaroslav Heger; Peter Patráš; Holger Kluge; Ji?í Brož

    2009-01-01

    A digestibility experiment was carried out on weanling piglets to study the effect of an enzyme complex with predominant xylanase activity on apparent ileal (AID) and apparent total tract digestibility of nutrients and energy. The enzyme was supplemented at four levels (0, 50, 100 and 200 mg\\/kg) to a diet containing 96% rye. There were significant effects of the added enzyme

  11. BILE ACIDS REGULATE THE ONTOGENIC EXPRESSION OF ILEAL BILE ACID BINDING PROTEIN IN THE RAT VIA THE FARNESOID X RECEPTOR

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the rat, an increase in ileal bile acid binding protein (IBABP) expression occurs during the third postnatal week. In vitro studies suggest that bile acids (BAs) increase IBABP transcription by activating the BA receptor, farnesoid X receptor (FXR). Thus, we investigated the role of BAs on the on...

  12. Effect of vitamin D or calcium deficiency on duodenal, jejunal and ileal calcium-binding protein and on plasma calcium

    E-print Network

    Paris-Sud XI, Université de

    Effect of vitamin D or calcium deficiency on duodenal, jejunal and ileal calcium-binding protein and on plasma calcium and 25-hydroxycholecalciferol levels in the growing pig Monique THOMASSET, A. POINTILLART Josas. Summary. In vitamin D-deficient pigs the amount of intestinal calcium-binding protein (Ca

  13. Incidence, risk factors, and treatment of dysplasia in the anal transitional zone after ileal pouch-anal anastomosis

    Microsoft Academic Search

    Yehiel Ziv; Victor W. Fazio; Mauro T. Sirimarco; Ian C. Lavery; John R. Goldblum; Robert E. Petras

    1994-01-01

    Preservation of the anal transitional zone (ATZ) after restorative proctocolectomy and stapled ileal pouch-anal anastomosis (IPAA) for ulcerative colitis is controversial. PURPOSE: To evaluate the incidence, risk factors, and treatment options for dysplasia and\\/or cancer after restorative proctocolectomy and stapled IPAA. METHODS: We reviewed the records of all 254 patients operated on for ulcerative colitis who had a restorative proctocolectomy,

  14. Effects of diet type and ingredient composition on rate of passage and apparent ileal amino acid digestibility in broiler chicks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This experiment evaluated rate of passage (ROP) and standardized ileal amino acid digestibility (SIAAD) of 4 diets varying in ingredient composition fed to broilers from 14 to 22 d of age. Two hundred and eighty-eight Ross × Ross 708 chicks (12 birds per pen; 0.45 m2 per bird) were randomly assigne...

  15. A technique of extending small-bowel mesentery for ileal pouch-anal anastomosis: report of a case.

    PubMed

    Metcalf, Dan R; Nivatvongs, Santhat; Sullivan, Timothy M; Suwanthanma, Weerapat

    2008-03-01

    One of the keys to success in proctocolectomy with ileal pouch-anal anastomosis is obtaining adequate mesenteric length to allow the pouch to reach the anorectum without tension. A multitude of techniques have been described in the literature to gain mesenteric length; however, in most cases these techniques only allow for the correction of a small deficit in the mesenteric length. We encountered a case in which the small-bowel mesentery was severely foreshortened because of a previous small-bowel volvulus just proximal to the loop ileostomy during recovery from the initial stage of his ileal pouch procedure. In this case, the deficit in length required an interposition vein graft to the superior mesenteric artery to facilitate adequate mesenteric length and allow completion of the ileal pouch-anal anastomosis. We report this technique to add another method of mesenteric lengthening to the armamentarium of surgeons performing ileal pouch-anal anastomoses. This technique should only be used as a last resort. PMID:18213491

  16. Evidence for early aging in the mucosal immune system.

    PubMed

    Koga, T; McGhee, J R; Kato, H; Kato, R; Kiyono, H; Fujihashi, K

    2000-11-01

    Despite recent advances in the cellular and molecular analysis of induction and regulation of mucosal immune responses, little is yet known about differences which occur in aging. To address this important issue, we have compared the mucosal and systemic immune responses of aged (12- to 14-mo- or 2-year-old) and young adult (6- to 8-wk-old) C57BL/6 mice. Both aged and young mice were immunized weekly with three oral doses of 1 mg of OVA and 10 microg of cholera toxin (CT) as mucosal adjuvant. Both groups of mice over 1 or 2 years of age showed reduced levels of Ag-specific mucosal or systemic immune responses at day 21. An Ag-specific B cell enzyme-linked immunospot assay confirmed these results at the cellular level. When the Ag-induced cytokine responses were examined at both protein and mRNA levels, CD4(+) T cells from spleen and Peyer's patches of young adult mice revealed elevated levels of IL-4 production; however, these cytokine responses were significantly diminished in aged mice. In contrast to mucosal immunization, mice s. c. immunized with OVA plus CT resulted in impaired OVA-specific but intact CT B subunit-specific immune responses in 12- to 14-mo-old mice although the responses to both Ags were depressed in 2-year-old mice. These results provide the first evidence that the development of age-associated alterations possibly occurs earlier in the mucosal immune system than in the systemic immune compartment. PMID:11046071

  17. 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

  18. New mucosal flap modification for endonasal endoscopic dacryocystorhinostomy in Asians

    PubMed Central

    Ji, Qing-Shan; Zhong, Jing-Xiang; Tu, Yun-Hai; Wu, Wen-Can

    2012-01-01

    AIM To describe a simple modification of fashioning the mucosal flap for endonasal endoscopic dacryocystorhinostomy (EES-DCR) in Asians and investigate its efficacy. METHODS A total of 120 patients with unilateral primary chronic dacryocystitis (PCD) were randomized into two groups: the new shaped nasal mucosal flap group (group A) and the removed nasal mucosal flap group (group B). All patients underwent standard EES-DCR. Patients in group A were performed a new shaped nasal mucosal flap covering the bared bone around the opened sac and those in group B was removed the nasal mucosal flap uncovering the bared bone. Patients were followed up for one year. The occurrence of granulation tissue, the proliferation of scar tissue and success rate of EES-DCR was compared. RESULTS In the present study, complete postoperative data were acquired from 54 patients in group A and from 57 patients in group B. During process of review, the occurrence of granulation tissue was at the ostium margins account for 15% (8/54) in group A and 39% (22/57) in group B (P<0.05). At the one-year review, scar tissue was present in 5 patients in group A compared with 18 in group B (P<0.05). The success rate of EES-DCR was 98% (53/54) in group A and 84% (48/57) in group B (P<0.05). CONCLUSION The simple modification of fashioning nasal mucosal flap can effectively cover the bared bone around the opened sac and reduce formation of granulation tissue, lessen the risk of scar tissue formation and closure of ostium, thus improve the success rate of EES-DCR in Asians. PMID:23275904

  19. Prevalence of Oral Mucosal Lesions in an Adult Iranian Population

    PubMed Central

    Mansour Ghanaei, Fariborz; Joukar, Farahnaz; Rabiei, Maryam; Dadashzadeh, Alireza; Kord Valeshabad, Ali

    2013-01-01

    Background Nowadays the importance of oral health to life quality is not obvious to anyone in our world. Oral lesions can interfere with daily social activities in involved patients through impacts on mastication, swallowing and speech and symptoms like xerostomia, halitosis or dysesthesia. Objectives To assess the prevalence and types of oral lesions in a general population in Rasht, Northern Province of Iran. Patients and Methods 1581 people aged > 30 years old who were inhabitant of Rasht, Iran, enrolled in a cross-sectional study. For each individual a detailed questionnaire based on the world health organization (WHO) guidelines in order to diagnosis of the lesions was filled and it contained all the required data. Participants were divided into two groups with and without oral mucosal lesions and oral mucosal lesions were divided into two groups with and without. Demographic characteristics and clinical information including age, sex, smoking (cigarette and tobacco), opium consumption, medication and oral and dental hygiene were collected and compared between these two groups. Results The prevalence of mucosal lesions in our study was 19.4%. Our data demonstrated higher prevalence of oral mucosal lesions in males and young adults (30-40 years). The most common mucosal lesion among our participants was Fissured tongue(4%), followed by Fordyce granules(2.8%), geographic tongue(2.6%) , Pigmentation(2.5%), Candida(1.8%), Smoker Plate(1.6%), lingual Varices(1.5%), Petechiae(1.4%) and lingual labial(1.4%) . Leukoplakia was observed only in two people (0.1%).No case of malignant lesions was detected. No statistically significant difference was confirmed between the two groups regarding smoking, opium consumption, medication and oral and dental hygiene. Conclusions Our data has provided baseline information about epidemiologic aspects of oral mucosal lesions which can be valuable in organized national program targeting on oral health and hygiene in the society. PMID:24396581

  20. Lead(II) Complex Formation with Glutathione

    PubMed Central

    Mah, Vicky

    2012-01-01

    A structural investigation of complexes formed between the Pb2+ ion and glutathione (GSH, denoted AH3 in its triprotonated form) the most abundant non2protein thiol in biological systems, was carried out for a series of aqueous solutions at pH 8.5 and CPb2+ = 10 mM, and in the solid state. The Pb LIII-edge EXAFS oscillation for a solid compound with the empirical formula [Pb(AH2)]ClO4 was modeled with one Pb-S and two short Pb-O bond distances at 2.64 ± 0.04 Å and 2.28 ± 0.04 Å, respectively. In addition Pb···Pb interactions at 4.15 ± 0.05 Å indicate dimeric species in a network where the thiolate group forms an asymmetrical bridge between two Pb2+ ions. In aqueous solution at the mole ratio GSH / Pb(II) = 2.0 (CPb2+ = 10 mM, pH 8.5), lead(II) complexes with two thiolate ligands form, characterized by a ligand-to-metal charge transfer band (LMCT) S- ? Pb2+ at 317 nm in the UV-vis spectrum and mean Pb-S and Pb-(N/O) bond distances of 2.65 ± 0.04 Å and 2.51 ± 0.04 Å, respectively, from a Pb LIII-edge EXAFS spectrum. For solutions with higher mole ratios, GSH / Pb(II) ? 3.0, ESI-MS spectra identified a trisglutathionyl lead(II) complex, for which Pb LIII-edge EXAFS spectroscopy shows a mean Pb-S distance of 2.65 ± 0.04 Å in PbS3 coordination, 207Pb NMR spectroscopy displays a chemical shift of 2793 ppm, and in the UV-vis spectrum an S- ? Pb2+ LMCT band appears at 335 nm. The complex persists at high excess of glutathione, and also at ~25 K in frozen glycerol (33%) / water glasses for GSH / Pb(II) mole ratios from 4.0 to 10 (CPb2+ = 10 mM) measured by Pb LIII-edge EXAFS spectroscopy. PMID:22594853

  1. Erosive mucosal lichen planus: response to topical treatment with tacrolimus.

    PubMed

    Vente, C; Reich, K; Rupprecht, R; Neumann, C

    1999-02-01

    Erosive mucosal lichen planus is a painful and disabling inflammatory skin disease that is highly resistant to topical treatment. We report on six patients with severe recalcitrant erosive mucosal lichen planus who benefited from topical application of tacrolimus ointment. After 4 weeks of treatment, complete resolution was observed in three cases, and substantial improvement was achieved in the other three patients. In these cases, prolonged treatment resulted either in further improvement or in complete healing. All patients reported rapid relief from pain and burning. No severe side-effects were observed. PMID:10233234

  2. Mucosal wrinkling in animal antra induced by volumetric growth

    NASA Astrophysics Data System (ADS)

    Li, Bo; Cao, Yan-Ping; Feng, Xi-Qiao; Yu, Shou-Wen

    2011-04-01

    Surface wrinkling of animal mucosas is crucial for the biological functions of some tissues, and the change in their surface patterns is a phenotypic characteristic of certain diseases. Here we develop a biomechanical model to study the relationship between morphogenesis and volumetric growth, either physiological or pathological, of mucosas. Theoretical analysis and numerical simulations are performed to unravel the critical characteristics of mucosal wrinkling in a spherical antrum. It is shown that the thicknesses and elastic moduli of mucosal and submucosal layers dictate the surface buckling morphology. The results hold clinical relevance for such diseases as inflammation and gastritis.

  3. [Epidemiology of H. pylori infection and gastric mucosal atrophy].

    PubMed

    Kikuchi, Shogo

    2013-08-01

    Progress in sanitary conditions, especially development of clean water supply for these 50 years has been reducing prevalence of Helicobacter pylori infection in Japan. The reduction in corporation with a less intake of highly salted foods and probably infection at later ages decreases prevalence and/or severity of gastric mucosal atrophy. Consequently, incidence of gastric cancer has been decreasing. However, it was unveiled that those with H. pylori infection and gastric mucosal atrophy have high risk of gastric cancer even after successful eradication of the infection, which still remains as a problem. PMID:23967661

  4. Mucosal interplay among commensal and pathogenic bacteria: lessons from Flagellin and Toll-like receptor 5

    E-print Network

    Paris-Sud XI, Université de

    1 Mucosal interplay among commensal and pathogenic bacteria: lessons from Flagellin and Toll; Innate immunity; Epithelium; Pathogenic bacteria; Commensal flora List of abbreviations: Dendritic cells molecular patterns expressed by the gut microbiota are essential in triggering TLR-dependent mucosal

  5. Development of a precision-fed ileal amino acid digestibility assay using 3-week-old broiler chicks.

    PubMed

    Kim, E J; Utterback, P L; Parsons, C M

    2011-02-01

    The objective of these studies was to develop a precision-fed ileal digestibility assay, primarily for amino acids (AA), using 3-wk-old broiler chicks. For all experiments, day-old Ross × Ross 708 broiler chicks were fed a standard corn-soybean meal starter diet until 21 d of age. In experiment 1, feed was removed and excreta were collected at 2, 4, 6, 8, 10, 12, and 14 h after feed withdrawal. Results indicated that 8 h of feed withdrawal was sufficient to empty the ileum of feed residues. In a subsequent experiment, chicks were fasted overnight for 10 h and then tube-fed various amounts (from 6 to 15 g) of a corn-soybean meal mixture (60:40). Ileal digesta from Meckel's diverticulum to the ileo-cecal junction were then collected at various collection times between 3 and 7 h postfeeding. Results indicated that the amount of digesta in the distal ileum was generally maximized by 4 h postfeeding and by feed intakes of 9 g or greater. Based on the results of the previous study, apparent and standardized ileal digestibility values of AA in a corn-soybean meal chick starter diet were then determined at 2, 3, and 4 h postfeeding. Digestibility values were similar for the 3- and 4-h collection times, but were numerically or significantly (P ? 0.05) lower at the 2-h collection time. The results of this study indicate that ileal AA digestibility can easily be determined in 3-wk-old broiler chicks when using a precision-fed assay. For such an assay, it is recommended that the chicks be fasted for at least 8 h before tube-feeding, that they be precision-fed approximately 10 g of feed, and that the ileal contents be collected at approximately 4 h postfeeding. PMID:21248337

  6. The Level of Protein in Milk Formula Modifies Ileal Sensitivity to LPS Later in Life in a Piglet Model

    PubMed Central

    Gras-Le Guen, Christèle; Lallès, Jean-Paul; Le Huërou-Luron, Isabelle; Boudry, Gaëlle

    2011-01-01

    Background Milk formulas have higher protein contents than human milk. This high protein level could modify the development of intestinal microbiota, epithelial barrier and immune functions and have long-term consequences. Methodology/Principal findings We investigated the effect of a high protein formula on ileal microbiota and physiology during the neonatal period and later in life. Piglets were fed from 2 to 28 days of age either a normoprotein (NP, equivalent to sow milk) or a high protein formula (HP, +40% protein). Then, they received the same solid diet until 160 days. During the formula feeding period ileal microbiota implantation was accelerated in HP piglets with greater concentrations of ileal bacteria at d7 in HP than NP piglets. Epithelial barrier function was altered with a higher permeability to small and large probes in Ussing chambers in HP compared to NP piglets without difference in bacterial translocation. Infiltration of T cells was increased in HP piglets at d28. IL-1? and NF-?B sub-units mRNA levels were reduced in HP piglets at d7 and d28 respectively; plasma haptoglobin also tended to be reduced at d7. Later in life, pro-inflammatory cytokines secretion in response to high doses of LPS in explants culture was reduced in HP compared to NP piglets. Levels of mRNA coding the NF-?B pathway sub-units were increased by the challenge with LPS in NP piglets, but not HP ones. Conclusions/Significance A high protein level in formula affects the postnatal development of ileal microbiota, epithelial barrier and immune function in piglets and alters ileal response to inflammatory mediators later in life. PMID:21573022

  7. Glutathione and glutathione reductase: a boon in disguise for plant abiotic stress defense operations.

    PubMed

    Gill, Sarvajeet Singh; Anjum, Naser A; Hasanuzzaman, Mirza; Gill, Ritu; Trivedi, Dipesh Kumar; Ahmad, Iqbal; Pereira, Eduarda; Tuteja, Narendra

    2013-09-01

    Abiotic stresses such as salinity, drought, clilling, heavy metal are the major limiting factors for crop productivity. These stresses induce the overproduction of reactive oxygen species (ROS) which are highly reactive and toxic, which must be minimized to protect the cell from oxidative damage. The cell organelles, particularly chloroplast and mitochondria are the major sites of ROS production in plants where excessive rate of electron flow takes place. Plant cells are well equipped to efficiently scavenge ROS and its reaction products by the coordinated and concerted action of antioxidant machinery constituted by vital enzymatic and non-enzymatic antioxidant components. Glutathione reductase (GR, EC 1.6.4.2) and tripeptide glutathione (GSH, ?-Glutamyl-Cysteinyl-Glycine) are two major components of ascorbate-glutathione (AsA-GSH) pathway which play significant role in protecting cells against ROS and its reaction products-accrued potential anomalies. Both GR and GSH are physiologically linked together where, GR is a NAD(P)H-dependent enzymatic antioxidant and efficiently maintains the reduced pool of GSH - a cellular thiol. The differential modulation of both GR and GSH in plants has been widely implicated for the significance of these two enigmatic antioxidants as major components of plant defense operations. Considering recent informations gained through molecular-genetic studies, the current paper presents an overview of the structure, localization, biosynthesis (for GSH only), discusses GSH and GR significance in abiotic stress (such as salinity, drought, clilling, heavy metal)-exposed crop plants and also points out unexplored aspects in the current context for future studies. PMID:23792825

  8. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7375 Glutathione reductase assay. (a) Identification....

  9. Immunolocalization of glutathione biosynthesis enzymes in Arabidopsis thaliana.

    PubMed

    Preuss, Mary L; Cameron, Jeffrey C; Berg, R Howard; Jez, Joseph M

    2014-02-01

    In plants, glutathione serves as a versatile redox buffer and cellular protective compound against a range of biotic and abiotic stresses. Glutathione production involves glutamate-cysteine ligase (GCL), the redox-regulated limiting enzyme of the pathway, and glutathione synthetase (GS). Because the sub-cellular and sub-organellar localization of these enzymes will have an impact on metabolism, here we examine the localization of GCL and GS in the leaves of Arabidopsis thaliana. Immuno-electron microscopy of leaf cells indicates localization of GCL primarily to the chloroplast with GS found in both the chloroplast and cytosol. Detailed examination of the localization of both enzymes within chloroplasts was performed using fractionation followed by immunoblot analysis and indicates that GCL and GS are found in the stroma. The localization of these enzymes to the stroma of chloroplasts has implications for the redox-regulation of GCL and plant glutathione biosynthesis. PMID:24361505

  10. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...Glutathione measurements are used in the diagnosis and treatment of certain drug-induced hemolytic (erythrocyte destroying) anemias due to an inherited enzyme deficiency. (b) Classification. Class I (general controls). The device is exempt...

  11. INTRODUCTION GLUTATHIONE (GSH), -L-glutamyl-L-cysteinyl-glycine,

    E-print Network

    Georgiou, George

    among prokaryotes is restricted to cyanobacteria and proteobacteria, as well as a few strains of gram concentrations (in the micromolar range). Some of the prokaryotes that lack glutathione seem to pro- duce

  12. Activity of Glutathione-Metabolizing and Antioxidant Enzymes in Malignant and Benign Tumors of Human Lungs

    Microsoft Academic Search

    R. N. Korotkina; G. N. Matskevich; A. Sh. Devlikanova; A. A. Vishnevskii; A. G. Kunitsyn; A. A. Karelin

    2002-01-01

    We measured the content of glutathione and activity of glutathione-metabolizing and antioxidant enzymes superoxide dismutase and catalase in samples obtained from 52 patients with malignant lung tumors and 20 patients with benign lung tumors. The content of glutathione and activity of glutathione-metabolizing enzymes underwent similar changes, but these changes were most pronounced in malignant tumors. Antioxidant enzyme activity changed insignificantly

  13. Changes in biosynthesis and metabolism of glutathione upon ochratoxin A stress in Arabidopsis thaliana.

    PubMed

    Wang, Yan; Zhao, Weiwei; Hao, Junran; Xu, Wentao; Luo, Yunbo; Wu, Weihong; Yang, Zhuojun; Liang, Zhihong; Huang, Kunlun

    2014-06-01

    Ochratoxin A (OTA) is one of the most toxic mycotoxins, which is toxic to plants and simulates oxidative stress. Glutathione is an important antioxidant in plants and is closely associated with detoxification in cells. We have previously shown that OTA exposure induces obvious expression differences in genes associated with glutathione metabolism. To characterize glutathione metabolism and understand its role in OTA phytotoxicity, we observed the accumulation of GSH in the detached leaves of Arabidopsis thaliana under OTA treatment. OTA stimulated a defense response through enhancing glutathione-S-transferase, glutathione peroxidase, glutathione reductase activities, and the transcript levels of these enzymes were increased to maintain the total glutathione content. Moreover, the level of oxidized glutathione (GSSG) was increased and the ascorbate-glutathione cycle fluctuated in response to OTA. The depletion of glutathione using buthionine sulfoximine (BSO, inhibitor of glutamate-cysteine ligase) had no profound effect on OTA toxicity, as glutathione was regenerated through the ascorbate-glutathione cycle to maintain the total glutathione content. The ROS, MDA and GSH accumulation was significantly affected in the mutant gsh1, gr1 and gpx2 after treatment with OTA, which indicated that glutathione metabolism is directly involved in the oxidative stress response of Arabidopsis thaliana subjected to OTA. In conclusion, date demonstrate that glutathione-associated metabolism is closely related with OTA stress and glutathione play a role in resistance of Arabidopsis subjected to OTA. PMID:24662377

  14. Glutathione Metabolic Genes Coordinately Respond to Heavy Metals and Jasmonic Acid in Arabidopsis

    Microsoft Academic Search

    Chengbin Xiang; David J. Oliver

    1998-01-01

    Glutathione plays a pivotal role in protecting plants from environmental stresses, oxidative stress, xenobiotics, and some heavy metals. Arabidopsis plants treated with cadmium or copper responded by increasing transcription of the genes for glutathione synthesis, g -glutamylcysteine synthetase and glutathione synthetase, as well as glutathione re- ductase. The response was specific for those metals whose toxicity is thought to be

  15. Induction of Mucosal B-Cell Memory by Intramuscular Inoculation of Mice with Rotavirus

    Microsoft Academic Search

    SUSAN E. COFFIN; PAUL A. OFFIT

    1998-01-01

    Despite significant efforts, the development of vaccines against mucosal pathogens has been slow. Previous studies have identified several obstacles to the successful development of mucosal vaccines. First, effector B- and T-cell responses at mucosal surfaces are relatively short-lived: mucosal immuno- globulin A (IgA) responses usually wane 4 to 6 months after a primary infection (3, 9, 17, 31), and effector

  16. Radiosensitization of Hypoxic Tumor Cells by Depletion of Intracellular Glutathione

    NASA Astrophysics Data System (ADS)

    Bump, Edward A.; Yu, Ning Y.; Brown, J. Martin

    1982-08-01

    Depletion of glutathione in Chinese hamster ovary cells in vitro by diethyl maleate resulted in enhancement of the effect of x-rays on cell survival under hypoxic conditions but not under oxygenated conditions. Hypoxic EMT6 tumor cells were similarly sensitized in vivo. The action of diethyl maleate is synergistic with the effect of the electron-affinic radiosensitizer misonidazole, suggesting that the effectiveness of misonidazole in cancer radiotherapy may be improved by combining it with drugs that deplete intracellular glutathione.

  17. 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

  18. Mucosal associated invariant T cells and the immune response to infection

    PubMed Central

    Gold, Marielle C.; Lewinsohn, David M.

    2011-01-01

    Mucosal associated invariant T cells are unique T cells localized at high frequencies at the portals of entry for many pathogens. Mucosal associated invariant T cells display a variety of characteristics that suggest their function is to act as effectors in the initial control of microbial infection at mucosal sites. PMID:21458588

  19. Preventing transmission: plant-derived microbicides and mucosal vaccines for reproductive health

    Microsoft Academic Search

    Kevin J. Whaley; Larry Zeitlin

    2005-01-01

    Exclusion of infectious agents from mucosal surfaces of the reproductive tract is a key objective of microbicides and mucosal vaccines. With mucosal antibodies as a common mechanism of exclusion, parallel development of passive and active immunization strategies is an opportunity to determine and achieve protective antibody concentrations in the female reproductive tract. Recognizing that access to sexual and reproductive health

  20. A dilemma for mucosal vaccination: efficacy versus toxicity using enterotoxin-based adjuvants

    Microsoft Academic Search

    Kohtaro Fujihashi; Toshiya Koga; Frederik W. van Ginkel; Yukari Hagiwara; Jerry R. McGhee

    2002-01-01

    In the development of mucosal vaccines, cholera toxin (CT) has been shown to be an effective adjuvant and to induce both mucosal and systemic immune responses via a Th2 cell-dependent pathway. However, a major concern for use of mucosal adjuvants such as CT is that this molecule is not suitable for use in humans because of its innate toxicity. Recent

  1. In vivo optical coherence tomographybased scoring of oral mucositis in human subjects: a pilot study

    E-print Network

    Chen, Zhongping

    with a negative impact on quality of life QOL and increased cost of care.2­5 OM is the most common distressing is characterized by mucosal changes, includ- ing erythema and ulceration, which cause oropharyngeal pain. Currently 1.1 Oropharyngeal Mucositis Oropharyngeal mucositis OM occurs in 30 to 75% of che- motherapy

  2. Sclerosing mesenteritis with occult ileal perforation: report of a case simulating extensive intra-abdominal malignancy.

    PubMed

    Mathew, John; McKenna, Frank; Mason, John; Haboubi, N Y; Borghol, Mahdy

    2004-11-01

    Sclerosing mesenteritis is a rare condition that is characterized by fibrosis affecting mainly small-bowel mesentery, which in extensive cases may mimic advanced intra-abdominal malignancy. Establishing the diagnosis in such cases is a clinical and histopathologic challenge. We report the successful management of a case of extensive sclerosing mesenteritis with occult ileal perforation, which was possibly the triggering cause. Severe complications occurred as a result of both the disease itself and its surgical treatment. Despite the complex course and life-threatening complications, a good prognosis can be expected. Although occasional recovery has been attributed to spontaneous regression and response to immunosuppressive therapy, a search for, and full eradication of, possible triggering focus is of paramount importance. PMID:15622594

  3. A rare case of jejuno-ileal intussusception secondary to a gastrointestinal stromal tumour

    PubMed Central

    Stout, Annabel; Santharam, Lakshmi; Mirza, Nazzia

    2015-01-01

    Gastrointestinal stromal tumours (GISTs) are rare tumours, making up 0.2–1% of gastrointestinal malignancies [Zakaria and Daradkeh (Jejunojejunal intussusception induced by a gastrointestinal stromal tumour. Case Rep Surg 2012;2022:173680)]. Their relative rarity combined with non-specific presentation results in tumours often remaining undiagnosed until surgery or histological examination [Martis et al. (A rare case of jejunojejunal intussusception in an adult. Indian J Surg 2013;75(Suppl 1):18–20)]. Presentation as a lead point for intussusception is particularly rare. We present the first case of GIST leading to intussusception at the jejuno-ileal junction in an otherwise well patient prior to presentation. Provisional diagnosis was made during emergency laparotomy, and confirmed through histological analysis. A typical immunohistochemical profile was identified, after which the patient was commenced on adjuvant imatinib therapy. We discuss classical presentation of intussusception and GIST. Further considerations of the investigation and treatment options of GISTs are also presented. PMID:25576166

  4. Induction of glutathione S-transferase and glutathione by toxic compounds and elicitors in reed canary grass.

    PubMed

    Urbanek, H; Majorowicz, H; Zalewski, M; Saniewski, M

    2005-07-01

    Treatment of read canary grass leaves with phenol, 4-chlorophenol, naphthalic anhydride and phenylethylisothiocyanate increased glutathione S-transferase activity by 1.4-2.4-fold (control 17 U g(-1) DW). Benzothiadiazole, beta-aminobutyric acid and salicylic acid increased activity by 1.3-1.8-fold. Total glutathione pool was increased by the toxic compounds by 1.2-2-fold and by the elicitors 1.4-1.6-fold (control 593 nmol g(-1) DW). Unlike the other compounds, benzothiadiazole and salicylic acid did not decrease the redox state. Benzothiadiazole acted synergistically with chlorophenol on glutathione S-transferase and glutathione levels and counteracted the decrease in redox state caused by the xenobiotic. Reed canary grass thus has a strong potential to neutralize toxic compounds, which may be further enhanced by elicitors. PMID:16091885

  5. Herbal substance, acteoside, alleviates intestinal mucositis in mice.

    PubMed

    Reinke, Daniel; Kritas, Stamatiki; Polychronopoulos, Panagiotis; Skaltsounis, Alexios L; Aligiannis, Nektarios; Tran, Cuong D

    2015-01-01

    This study investigated the role of acteoside in the amelioration of mucositis. C57BL/6 mice were gavaged daily with acteoside 600??g for 5?d prior to induction of mucositis and throughout the experimental period. Mucositis was induced by methotrexate (MTX; 12.5?mg/kg; s.c.). Mice were culled on d 5 and d 11 after MTX. The duodenum, jejunum, and ileum were collected for myeloperoxidase (MPO) activity, metallothionein (MT) levels, and histology. Acteoside reduced histological severity scores by 75, 78, and 88% in the duodenum, jejunum, and ileum, respectively, compared to MTX-controls on d 5. Acteoside reduced crypt depth by 49, 51, and 33% and increased villus height by 19, 38, and 10% in the duodenum, jejunum, and ileum, respectively, compared to MTX-controls on d 5. Acteoside decreased MT by 50% compared to MTX-control mice on d 5. Acteoside decreased MPO by 60% and 30% in the duodenum and jejunum, respectively, compared to MTX-controls on d 5. Acteoside alleviated MTX-induced small intestinal mucositis possibly by preventing inflammation. PMID:25628651

  6. Predictors of Esophageal Stricture Formation Post Endoscopic Mucosal Resection

    PubMed Central

    Qumseya, Bashar; Panossian, Abraham M.; Rizk, Cynthia; Cangemi, David; Wolfsen, Christianne; Raimondo, Massimo; Woodward, Timothy; Wallace, Michael B.

    2014-01-01

    Background/Aims Stricture formation is a common complication after endoscopic mucosal resection. Predictors of stricture formation have not been well studied. Methods We conducted a retrospective, observational, descriptive study by using a prospective endoscopic mucosal resection database in a tertiary referral center. For each patient, we extracted the age, sex, lesion size, use of ablative therapy, and detection of esophageal strictures. The primary outcome was the presence of esophageal stricture at follow-up. Multivariate logistic regression was used to analyze the association between the primary outcome and predictors. Results Of 136 patients, 27% (n=37) had esophageal strictures. Thirty-two percent (n=44) needed endoscopic dilation to relieve dysphagia (median, 2; range, 1 to 8). Multivariate logistic regression analysis showed that the size of the lesion excised is associated with increased odds of having a stricture (odds ratio, 1.6; 95% confidence interval, 1.1 to 2.3; p=0.01), when controlling for age, sex, and ablative modalities. Similarly, the number of lesions removed in the index procedure was associated with increased odds of developing a stricture (odds ratio, 2.3; 95% confidence interval, 1.3 to 4.2; p=0.007). Conclusions Stricture formation after esophageal endoscopic mucosal resection is common. Risk factors for stricture formation include large mucosal resections and the resection of multiple lesions on the initial procedure. PMID:24765598

  7. Individual mammalian mucosal glucosidase subunits digest various starch structures differently

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Starch digestion in the human body requires two luminal enzymes,salivary and pancreatic alpha-amylase (AMY), and four small intestinal mucosal enzyme activities related to the maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) complexes. Starch consists of two polysaccharides, amylose (AM) and ...

  8. Endoscopic mucosal resection for treatment of early gastric cancer

    Microsoft Academic Search

    H Ono; H Kondo; T Gotoda; K Shirao; H Yamaguchi; D Saito; K Hosokawa; T Shimoda; S Yoshida

    2001-01-01

    BACKGROUNDIn Japan, endoscopic mucosal resection (EMR) is accepted as a treatment option for cases of early gastric cancer (EGC) where the probability of lymph node metastasis is low. The results of EMR for EGC at the National Cancer Center Hospital, Tokyo, over a 11 year period are presented.METHODSEMR was applied to patients with early cancers up to 30 mm in

  9. Neuroselective Current Perception Threshold Evaluation of Bladder Mucosal Sensory Function

    Microsoft Academic Search

    Osamu Ukimura; So Ushijima; Hisashi Honjo; Tsuyoshi Iwata; Kei Suzuki; Naoki Hirahara; Koji Okihara; Yoichi Mizutani; Akihiro Kawauchi; Tsuneharu Miki

    2004-01-01

    Objective: To evaluate human bladder mucosal sensory function by neuroselective Current Perception Threshold (CPT) measures from healthy and neuropathic bladders.Methods: Eight healthy volunteers and 38 patients with urinary symptoms underwent conventional urodynamic tests including water-filling cystometry and ice water test. Standardized neuroselective CPT measures were obtained from the left index finger and the mucosa of the posterior bladder wall. Three

  10. Mucosal reactivity to cow's milk protein in coeliac disease

    PubMed Central

    Kristjánsson, G; Venge, P; Hällgren, R

    2007-01-01

    Patients with coeliac disease (CD) on a gluten-free diet may still have gastrointestinal symptoms. On clinical grounds cow's milk (CM) protein sensitivity may be suspected. Here, using rectal protein challenge, we investigated the local inflammatory reaction to gluten and CM protein in adult patients with CD in remission. Rectal challenges with wheat gluten and dried CM powder were performed in 20 patients with CD and 15 healthy controls. Fifteen hours after challenge the mucosal reaction was recorded by the mucosal patch technique with measurements of local release of neutrophil and eosinophil granule constituents; myeloperoxidase (MPO) and eosinophil cationic protein (ECP). We measured the mucosal production of nitric oxide (NO) simultaneously. Six of the patients who reacted to CM were also challenged with ?-lactalbumin and casein. In 18 of 20 patients gluten challenge induced neutrophil activation defined as increased MPO release and increased NO synthesis. Ten of these 20 patients showed a similarly strong inflammatory reaction to CM challenge. Six of the CM sensitive patients were challenged with specific CM proteins: casein and ?-lactalbumin. Casein, in contrast to ?-lactalbumin, induced an inflammatory response similar to that produced by CM. A mucosal inflammatory response similar to that elicited by gluten was produced by CM protein in about 50% of the patients with coeliac disease. Casein, in particular, seems to be involved in this reaction. PMID:17302893

  11. Activation of the mucosal immune system in irritable bowel syndrome

    Microsoft Academic Search

    Vinton S. Chadwick; Wangxue Chen; Dairu Shu; Barbara Paulus; Peter Bethwaite; Andy Tie; Ian Wilson

    2002-01-01

    Background & Aims: A role for the mucosal immune system in the pathogenesis of irritable bowel syndrome is suggested by its association with intestinal infections. Methods: To investigate this, we performed histologic and immunohistologic studies on colonoscopic biopsy specimens from 77 patients with symptoms satisfying the Rome criteria and 28 asymptomatic control patients. Results: Histologic assessment of biopsy specimens from

  12. Small intestinal mucosal abnormalities in post-perinatal deaths

    Microsoft Academic Search

    S Variend; R Sunderland

    1984-01-01

    Examination of small intestinal mucosa from cases of post-perinatal death in Sheffield between September 1980 and September 1981 showed mucosal changes before death in 18 of 78 cases (20%). There was no significant difference in prevalence between explained and unexplained deaths, nor was there any positive association with viral isolation from the small intestine. The lesion was much more common

  13. Herbal Substance, Acteoside, Alleviates Intestinal Mucositis in Mice

    PubMed Central

    Reinke, Daniel; Kritas, Stamatiki; Polychronopoulos, Panagiotis; Skaltsounis, Alexios L.; Aligiannis, Nektarios; Tran, Cuong D.

    2015-01-01

    This study investigated the role of acteoside in the amelioration of mucositis. C57BL/6 mice were gavaged daily with acteoside 600??g for 5?d prior to induction of mucositis and throughout the experimental period. Mucositis was induced by methotrexate (MTX; 12.5?mg/kg; s.c.). Mice were culled on d 5 and d 11 after MTX. The duodenum, jejunum, and ileum were collected for myeloperoxidase (MPO) activity, metallothionein (MT) levels, and histology. Acteoside reduced histological severity scores by 75, 78, and 88% in the duodenum, jejunum, and ileum, respectively, compared to MTX-controls on d 5. Acteoside reduced crypt depth by 49, 51, and 33% and increased villus height by 19, 38, and 10% in the duodenum, jejunum, and ileum, respectively, compared to MTX-controls on d 5. Acteoside decreased MT by 50% compared to MTX-control mice on d 5. Acteoside decreased MPO by 60% and 30% in the duodenum and jejunum, respectively, compared to MTX-controls on d 5. Acteoside alleviated MTX-induced small intestinal mucositis possibly by preventing inflammation. PMID:25628651

  14. A case of radiation recall mucositis associated with docetaxel

    Microsoft Academic Search

    Laura R. Culp; Anna M. Pou; Dennie V. Jones; John Bayouth; Giuseppe Sanguineti

    2004-01-01

    Background. Radiation recall reactions, in particu- lar dermatitis, are well documented in the literature. However, radiation recall mucositis is a rare clinical phenomenon. Methods. We report a case of a 45-year-old man diagnosed with squamous cell carcinoma of the base of tongue. He was treated with surgery followed by chemotherapy and radiation therapy. Several months after completing treatment, he had

  15. Postdoctoral Research Positions in Mucosal Immunology and Molecular Microbiology

    E-print Network

    Symington, Lorraine S.

    Postdoctoral Research Positions in Mucosal Immunology and Molecular Microbiology Two post-doctoral research positions are available at the Department of Microbiology and Immunology, Columbia University, New the challenge of working at the interface between Immunology and Microbiology. The selected candidates will work

  16. Pharmacological Protection From Radiation {+-} Cisplatin-Induced Oral Mucositis

    SciTech Connect

    Cotrim, Ana P. [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Yoshikawa, Masanobu [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa (Japan); Sunshine, Abraham N.; Zheng Changyu [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Sowers, Anastasia L.; Thetford, Angela D.; Cook, John A.; Mitchell, James B. [Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Baum, Bruce J., E-mail: bbaum@dir.nidcr.nih.gov [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)

    2012-07-15

    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 and 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.

  17. Mucosal Immunity: Its Role in Defense and Allergy

    Microsoft Academic Search

    Helena Tlaskalová-Hogenová; Bozena Cukrowska; David P. Funda; Hana Kozáková; Ilja Trebichavský; Dan Sokol; Petra Fundová; Dana Horáková; Lenka Jelínková; Daniel Sánchez

    2002-01-01

    The interface between the organism and the outside world, which is the site of exchange of nutrients, export of products and waste components, must be selectively permeable and at the same time, it must constitute a barrier equipped with local defense mechanisms against environmental threats (e.g. invading pathogens). The boundaries with the environment (mucosal and skin surfaces) are therefore covered

  18. Nature of the Thymus Dependency of Mucosal Mast Cells

    Microsoft Academic Search

    G. Mayrhofer; H. Bazin

    1981-01-01

    Mucosal mast cells have been examined in the small intestinal mucosae of nude mice and nude rats, B rats and a child with the Di George syndrome. In all three species, mast cells were present in normal numbers despite the athymic status of the nude mice and nude rats, the vestigial nature of the thymus in the child, and the

  19. Differential Injury Responses in Oral Mucosal and Cutaneous Wounds

    Microsoft Academic Search

    A. M. Szpaderska; J. D. Zuckerman; L. A. DiPietro

    2003-01-01

    Oral mucosa heals faster than does skin, yet few studies have compared the repair at oral mucosal and cutaneous sites. To determine whether the privileged healing of oral injuries involves a differential inflammatory phase, we compared the inflammatory cell infiltrate and cytokine production in wounds of equivalent size in oral mucosa and skin. Significantly lower levels of macrophage, neutrophil, and

  20. Calprotectin Expression Inhibits Bacterial Binding to Mucosal Epithelial Cells

    Microsoft Academic Search

    KANOKWAN NISAPAKULTORN; KAREN F. ROSS; MARK C. HERZBERG

    2001-01-01

    Squamous mucosal epithelial cells constitutively express calprotectin in the cytoplasm. To study how this antimicrobial protein complex confers epithelial resistance to invading bacteria, an epithelial cell line was stably transfected to express the calprotectin complex. Cells expressing calprotectin resist invasion by Listeria monocytogenes and Salmonella enterica serovar Typhimurium. Calprotectin expression was accompanied by altered actin organization, increased a3 integrin expression,

  1. Ileal digestibility of amino acids in coproducts of corn processing into ethanol for pigs.

    PubMed

    Adeola, O; Ragland, D

    2012-12-01

    Five barrows with an average initial BW of 45 kg and fitted with a T-cannula at the distal ileum were fed 5 diets to determine the standardized ileal digestibility (SID) of AA in corn (Zea mays) distillers' dried grains (DDG), DDG with solubles (DDGS), high-protein DDG (HPDDG) and high-protein DDGS (HPDDGS). On a DM basis, the test ingredients contained 33.7% CP, 19.2% ADF, and 53.1% NDF for DDG; 30.3% CP, 11.8% ADF, and 40.6% NDF for DDGS; 62.5% CP, 28.4% ADF, and 45.1% NDF for HPDDG; and 52.4% CP, 17.4% ADF, and 30.4% NDF for HPDDGS. The 5 diets consisted of a N-free diet (NFD) and 4 semipurified diets, in which the test ingredient was the sole protein source with chromic oxide added at 5 g/kg as an indigestible marker, and fed for each of 5 periods. The NFD was used to determine basal endogenous AA losses. Each period consisted of a 5-d adjustment period and 2 d of ileal digesta collection for 10 h on each of day 6 and day 7. Amino acids in the test ingredients were well digested by pigs and SID of Lys for DDG, DDGS, HPDDG, and HPDDGS were 88.6, 79.9, 94.6, and 85.8%, respectively. Corresponding values for were Met 93.9, 92.8, 97.1, and 94.6%. The SID of Lys was greater (P < 0.05) in HPDDG than DDGS. In general, digestibility of AA in the high-protein coproduct of the dry grind processing of corn into ethanol was 2 to 8 percentage units more than in the regular coproduct and 2 to 9 percentage units less in the coproduct with added solubles. PMID:23365291

  2. Ileal FGF15 contributes to fibrosis-associated hepatocellular carcinoma development.

    PubMed

    Uriarte, Iker; Latasa, M Ujue; Carotti, Simone; Fernandez-Barrena, Maite G; Garcia-Irigoyen, Oihane; Elizalde, Maria; Urtasun, Raquel; Vespasiani-Gentilucci, Umberto; Morini, Sergio; de Mingo, Alvaro; Mari, Montserrat; Corrales, Fernando J; Prieto, Jesus; Berasain, Carmen; Avila, Matias A

    2015-05-15

    Fibroblast growth factor 15 (FGF15), FGF19 in humans, is a gut-derived hormone and a key regulator of bile acids and carbohydrate metabolism. FGF15 also participates in liver regeneration after partial hepatectomy inducing hepatocellular proliferation. FGF19 is overexpressed in a significant proportion of human hepatocellular carcinomas (HCC), and activation of its receptor FGFR4 promotes HCC cell growth. Here we addressed for the first time the role of endogenous Fgf15 in hepatocarcinogenesis. Fgf15(+/) (+) and Fgf15(-/-) mice were subjected to a clinically relevant model of liver inflammation and fibrosis-associated carcinogenesis. Fgf15(-/-) mice showed less and smaller tumors, and histological neoplastic lesions were also smaller than in Fgf15(+/) (+) animals. Importantly, ileal Fgf15 mRNA expression was enhanced in mice undergoing carcinogenesis, but at variance with human HCC it was not detected in liver or HCC tissues, while circulating FGF15 protein was clearly upregulated. Hepatocellular proliferation was also reduced in Fgf15(-/-) mice, which also expressed lower levels of the HCC marker alpha-fetoprotein (AFP). Interestingly, lack of FGF15 resulted in attenuated fibrogenesis. However, in vitro experiments showed that liver fibrogenic stellate cells were not direct targets for FGF15/FGF19. Conversely we demonstrate that FGF15/FGF19 induces the expression of the pro-fibrogenic and pro-tumorigenic connective tissue growth factor (CTGF) in hepatocytes. These findings suggest the existence of an FGF15-triggered CTGF-mediated paracrine action on stellate cells, and an amplification mechanism for the hepatocarcinogenic effects of FGF15 via CTGF production. In summary, our observations indicate that ileal FGF15 may contribute to HCC development in a context of chronic liver injury and fibrosis. PMID:25346390

  3. Association between gastro-intestinal symptoms and menstruation in patients with ileal pouches

    PubMed Central

    Bharadwaj, Shishira; Wu, Xian-rui; Barber, Matthew D.; Queener, Elaine; Graff, Lesley; Shen, Bo

    2014-01-01

    Background and aims: Gastro-intestinal (GI) symptoms are often experienced by healthy women during menstruation. An increased frequency of GI symptoms during menses has also been reported in women with irritable bowel syndrome or inflammatory bowel disease (IBD); however, IBD patients with restorative proctocolectomy and ileal pouch-anal anastomoses (IPAA) have not been studied. We aimed to examine the association between GI symptoms before and during menses in patients with IPAA, and to assess factors for exacerbation of GI symptoms in those patients. Methods: Adult women recorded in the Pouchitis Registry were invited to participate in a mailed survey. Participants reported on GI symptoms 1–5 days prior to- (pre-menses) and during the days of their menses in recent months. Demographic and clinical variables were obtained through the survey and chart review. Results: One hundred and twenty-eight (21.3%) out of 600 women with IPAA responded to the survey questionnaire. Forty-three (33.5%) were excluded for reasons including post-menopausal (n = 25), hysterectomy (n = 14) and use of contraceptives (n = 4). Abdominal pain (P = 0.001), diarrhea (P = 0.021), and urgency (P = 0.031) were more commonly reported during menses than pre-menses by the participants. Only a history of painful menses was significantly associated with increased GI symptoms during menses for patients with ileal pouch (odds ratio = 5.67; 95% confidence interval: 1.41–22.88; P = 0.015). Conclusion: GI symptoms such as abdominal pain, diarrhea, and urgency are commonly associated with menses in patients with ileo-anal pouch. Painful menses may be associated with worsening of GI symptoms. PMID:25016379

  4. Retubularization of the ileocystoplasty patch for conversion into an ileal conduit

    PubMed Central

    Massaro, Peter A.; Gajewski, Jerzy B.; Bailly, Greg

    2013-01-01

    Introduction: We present the outcomes and long-term follow-up of patients who underwent conversion to an ileal conduit urinary diversion using the retubularized patch from the initial augmentation ileocystoplasty. Methods: We reviewed the charts of all patients who underwent this surgery at our centre. The indications for surgery, workup, clinical outcomes and complication rates were assessed. Patient-reported symptom response based on global response assessment (GRA) was determined and used as a subjective measure of overall treatment effectiveness. Results: Thirteen patients with either bladder pain syndrome/interstitial cystitis (BPS/IC) (n = 11) or neurogenic bladder (n = 2) were followed for a mean of 80 months. The most common indication for surgical conversion was persistent lower urinary tract symptoms (LUTS) or bladder pain. Late complications were frequent, typically low-grade, and usually manageable with conservative therapy; the most common were urinary tract infections (n = 6) and parastomal hernias (n = 5). Two patients developed ureteric strictures. Nine of 13 patients required additional surgery to manage complications or persistent symptoms. Only 5 of 11 GRA respondents reported a successful therapeutic outcome and BPS/IC patients who underwent concurrent cystourethrectomy tended to be most satisfied (2/3). Nevertheless, several patients still achieved symptom control when no other treatment options were available to them. Conclusion: Conversion to an ileal conduit using the retubularized ileocystoplasty patch offers several technical and therapeutic advantages over creating a urinary diversion from a new bowel segment. It should therefore be considered a viable treatment option in patients who have exhausted more conservative management of their LUTS. PMID:23914260

  5. Effects of a phytogenic feed additive on growth performance and ileal nutrient digestibility in broiler chickens.

    PubMed

    Amad, A A; Männer, K; Wendler, K R; Neumann, K; Zentek, J

    2011-12-01

    A study was undertaken to examine the effects of a phytogenic feed additive (PFA) containing essential oils of thyme and star anise as lead active components on the growth performance and apparent ileal nutrient digestibility in broiler chickens. In total, 528 one-day-old Cobb male broilers were randomly divided into 4 dietary treatment groups with 6 replicate pens per treatment group (22 birds each). The dietary treatments were a control starter and grower basal diet without PFA or 150, 750, or 1,500 mg/kg of PFA. Body weight, weight gain, and feed intake were not significantly influenced by the feed additive, but the feed conversion ratio during the grower (22-42 d) and overall (1-42 d) periods improved linearly (P < 0.05) by the administration of PFA compared with that of the control diet. The average weights of the liver, heart, kidneys, and spleen were not significantly affected by the PFA. The results of the apparent ileal digestibility of crude ash, CP, crude fat, calcium, and phosphorus showed a linear increase (P < 0.05) related to the increase of PFA dose in the diet. Therefore, the means of digestibility of these nutrients were significantly higher in birds fed the PFA for all categories of age compared with the digestibility of these nutrients in the controls. In conclusion, the mode of action of the tested PFA can be explained by an improvement in the nutrient digestibility in the small intestine. The underlying physiological mechanisms, however, need to be characterized further. PMID:22080020

  6. Complications after ileal pouch-anal anastomosis in Korean patients with ulcerative colitis

    PubMed Central

    Ryoo, Seung-Bum; Oh, Heung-Kwon; Han, Eon Chul; Ha, Heon-Kyun; Moon, Sang Hui; Choe, Eun Kyung; Park, Kyu Joo

    2014-01-01

    AIM: To investigate the outcomes of treatments for complications after ileal pouch-anal anastomosis (IPAA) in Korean patients with ulcerative colitis. METHODS: Between March 1998 and February 2013, 72 patients (28 male and 44 female, median age 43.0 years ± 14.0 years) underwent total proctocolectomy with IPAA. The study cohort was registered prospectively and analyzed retrospectively. Patient characteristics, medical management histories, operative findings, pathology reports and postoperative clinical courses, including early postoperative and late complications and their treatments, were reviewed from a medical record system. All of the ileal pouches were J-pouch and were performed with either the double-stapling technique (n = 69) or a hand-sewn (n = 3) technique. RESULTS: Thirty-one (43.1%) patients had early complications, with 12 (16.7%) patients with complications related to the pouch. Pouch bleeding, pelvic abscesses and anastomosis ruptures were managed conservatively. Patients with pelvic abscesses were treated with surgical drainage. Twenty-seven (38.0%) patients had late complications during the follow-up period (82.5 ± 50.8 mo), with 21 (29.6%) patients with complications related to the pouch. Treatment for pouchitis included antibiotics or anti-inflammatory drugs. Pouch-vaginal fistulas, perianal abscesses or fistulas and anastomosis strictures were treated surgically. Pouch failure developed in two patients (2.8%). Analyses showed that an emergency operation was a significant risk factor for early pouch-related complications compared to elective procedures (55.6% vs 11.1%, P < 0.05). Pouchitis was related to early (35.3%) and the other late pouch-related complications (41.2%) (P < 0.05). The complications did not have an effect on pouch failure nor pouch function. CONCLUSION: The complications following IPAA can be treated successfully. Favorable long-term outcomes were achieved with a lower pouch failure rate than reported in Western patients. PMID:24966620

  7. Effects of selenium and mercury on glutathione and glutathione-dependent enzymes in experimental quail

    SciTech Connect

    Di Simplicio, P.; Leonzio, D.

    1989-01-01

    The protecting effect of selenium against the toxicity of methylmercury (MM) and mutual Se-Hg antagonism has long been known. The defensive action of Se does not occur by greater Hg body excretion but by a rearrangement in the accumulation pattern of Hg in organs. According to some authors, the Se-Hg interaction is brought about by endogenous glutathione (GSH) which in reducing selenite to selenide favors the formation of bis-methylmercury selenide. The high lipoaffinity of this compound alters the metabolism and distribution of mercury in critical tissues and thus its toxicity. The function of GSH as a protective agent against MM toxicity has recently been confirmed. GST is an important family of isozenzymes with binding properties which metabolize drugs and xenobiotics. These enzymes could indeed have an important function in Se-Hg antagonism. Their participation in conjugation with GSH and bile excretion of MM has been suggested by Refsvik although other authors seem to exclude it. In the present paper the behavior of GST isoenzymes in quail liver after combined Se-Hg treatment was studied; in addition other enzymes which regulate the GSH metabolism as well as the hapatic levels of Se, Hg, GSH and oxidized glutathione (GSSG) have been investigated.

  8. Modulation of cadmium-induced oxidative stress in Ceratophyllum demersum by zinc involves ascorbate–glutathione cycle and glutathione metabolism

    Microsoft Academic Search

    Parameswaran Aravind; Majeti Narasimha Vara Prasad

    2005-01-01

    To understand the interaction between Zn, an essential micronutrient and Cd, a non-essential element, Cd-10 ?M and Zn supplemented (10, 50, 100, and 200 ?M) Cd 10 ?M treated Ceratophyllum demersum L. (Coontail), a free floating freshwater macrophyte was chosen for the study. Cadmium at 10 ?M concentration decreased thiol content, enhanced oxidation of ascorbate (AsA) and glutathione (GSH) to dehydroascorbate (DHA) and glutathione

  9. Inhibition and recognition studies on the glutathione-binding site of equine liver glutathione S-transferase.

    PubMed Central

    D'Silva, C

    1990-01-01

    Equine liver glutathione S-transferase has been shown to consist of two identical subunits of apparent Mr 25,500 and a pl of 8.9. Kinetic data at pH 6.5 with 1-chloro-2,4-dinitrobenzene as a substrate suggests a random rapid-equilibrium mechanism, which is supported by inhibition studies using glutathione analogues. S-(p-Bromobenzyl)glutathione and the corresponding N alpha-, CGlu- and CGly-substituted derivatives have been found, at pH 6.5, to be linear competitive inhibitors, with respect to GSH, of glutathione transferase. N-Acetylation of S-(p-bromobenzyl)glutathione decreases binding by 100-fold, whereas N-benzoylation and N-benzyloxycarbonylation abolish binding of the derivative to the enzyme. The latter effect has been attributed to a steric constraint in this region of the enzyme. Amidation of the glycine carboxy group of S-(p-bromobenzyl)glutathione decreases binding by 13-fold, whereas methylation decreases binding by 70-fold, indicating a steric constraint and a possible electrostatic interaction in this region of the enzyme. Amidation of both carboxy groups decreases binding significantly by 802-fold, which agrees with electrostatic interaction of the glutamic acid carboxy group with a group located on the enzyme. PMID:2222409

  10. Treatment of KIT-mutated metastatic mucosal melanoma.

    PubMed

    Kim, Kevin B; Alrwas, Anas

    2014-09-01

    Mucosal melanoma is a rare, aggressive histologic subtype of malignant melanoma, and prognosis for patients with metastatic mucosal melanoma is very poor. In general, conventional cytotoxic agents alone or in combination with immunologic drugs have limited clinical benefit. Advances in molecular analytic techniques have helped researchers discover genetic aberrations in KIT, a receptor tyrosine kinase, in nearly 40% of patients with mucosal melanoma. Preclinical studies have demonstrated that hot-spot mutations, mostly substitutions in exons 11 and 13, result in constitutive activation of KIT and its downstream signal transduction pathways, such as the MEK/ERK, PI3K/AKT and JAK/STAT pathways. KIT inhibitors, most notably imatinib, have shown promising clinical activity in KIT-mutant advanced melanoma, including mucosal melanoma, with clinical response rates exceeding 35% in patients with hot-spot mutations in exon 11 or 13 and/or a high mutant/wild-type allelic ratio. However, the duration of disease control is rather short in general, and treatment with KIT inhibitors as single agents is not optimal. Well-designed mechanistic studies aimed at assessing molecular differences between various KIT mutations or other aberrations and mechanisms of resistance are urgently needed to improve KIT-targeting therapy for melanoma. In addition, with availability of checkpoint inhibitors, such as anti-CTLA4 and/or anti-PD-1 antibodies, immunotherapies using those inhibitors alone or in combinations of such immunotherapies with KIT inhibitors may lead to more effective therapeutic regimens. This review discusses the rationale for KIT inhibitor therapy in patients with metastatic mucosal melanoma and the findings of preclinical and clinical studies of KIT inhibitors in this patient population. PMID:25841461

  11. Mucosal healing and deep remission: What does it mean?

    PubMed Central

    Rogler, Gerhard; Vavricka, Stephan; Schoepfer, Alain; Lakatos, Peter L

    2013-01-01

    The use of specific terms under different meanings and varying definitions has always been a source of confusion in science. When we point our efforts towards an evidence based medicine for inflammatory bowel diseases (IBD) the same is true: Terms such as “mucosal healing” or “deep remission” as endpoints in clinical trials or treatment goals in daily patient care may contribute to misconceptions if meanings change over time or definitions are altered. It appears to be useful to first have a look at the development of terms and their definitions, to assess their intrinsic and context-independent problems and then to analyze the different relevance in present-day clinical studies and trials. The purpose of such an attempt would be to gain clearer insights into the true impact of the clinical findings behind the terms. It may also lead to a better defined use of those terms for future studies. The terms “mucosal healing” and “deep remission” have been introduced in recent years as new therapeutic targets in the treatment of IBD patients. Several clinical trials, cohort studies or inception cohorts provided data that the long term disease course is better, when mucosal healing is achieved. However, it is still unclear whether continued or increased therapeutic measures will aid or improve mucosal healing for patients in clinical remission. Clinical trials are under way to answer this question. Attention should be paid to clearly address what levels of IBD activity are looked at. In the present review article authors aim to summarize the current evidence available on mucosal healing and deep remission and try to highlight their value and position in the everyday decision making for gastroenterologists. PMID:24282345

  12. Clinical Experience with the N-shaped Ileal Neobladder: Assessment of Complications, Voiding Patterns, and Quality of Life in Our Series of 58 Patients

    Microsoft Academic Search

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

    2005-01-01

    Purpose: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.

  13. Measurement of oral mucositis in children: a review of the literature

    Microsoft Academic Search

    Deborah Tomlinson; Peter Judd; Eleanor Hendershot; Anne-Marie Maloney; Lillian Sung

    2007-01-01

    Goals of work  The assessment of oral mucositis is important. There is a paucity of validated oral mucositis assessment instruments for use\\u000a in children. This paper reviews the available mucositis measurement tools and their applicability to a paediatric population.\\u000a \\u000a \\u000a \\u000a Materials and methods  Literature search of PUBMED™ and bibliography searches identified articles relevant to mucositis measurement tools and the\\u000a measurement of mucositis in

  14. Mucosal immunity and protection against HIV/SIV infection: strategies and challenges for vaccine design

    PubMed Central

    Demberg, Thorsten; Robert-Guroff, Marjorie

    2012-01-01

    To date most HIV vaccine strategies have focused on parenteral immunization and systemic immunity. These approaches have not yielded the efficacious HIV vaccine urgently needed to control the AIDS pandemic. As HIV is primarily mucosally transmitted, efforts are being refocused on mucosal vaccine strategies, in spite of complexities of immune response induction and evaluation. Here we outline issues in mucosal vaccine design and illustrate strategies with examples from the recent literature. Development of a successful HIV vaccine will require in depth understanding of the mucosal immune system, knowledge that ultimately will benefit vaccine design for all mucosally transmitted infectious agents. PMID:19241252

  15. Biochem. J. (2001) 360, 345354 (Printed in Great Britain) 345 Microsomal glutathione S-transferase A1-1 with glutathione peroxidase

    E-print Network

    Omiecinski, Curtis

    -transferase A1-1 with glutathione peroxidase activity from sheep liver: molecular cloning, expression (microsomal GSTA1-1) with a significant selenium-independent glutathione peroxidase activity has been isolated peroxidase; GST, glutathione S-transferase; 4-HNE, 4-hydroxynonenal; NEM, N-ethylmaleimide; non

  16. Glutathione deficiency down-regulates hepatic lipogenesis in rats

    PubMed Central

    2010-01-01

    Background Oxidative stress is supposed to increase lipid accumulation by stimulation of hepatic lipogenesis at transcriptional level. This study was performed to investigate the role of glutathione in the regulation of this process. For that purpose, male rats were treated with buthionine sulfoximine (BSO), a specific inhibitor of ?-glutamylcysteine synthetase, for 7 days and compared with untreated control rats. Results BSO treatment caused a significant reduction of total glutathione in liver (-70%), which was attributable to diminished levels of reduced glutathione (GSH, -71%). Glutathione-deficient rats had lower triglyceride concentrations in their livers than the control rats (-23%), whereas the circulating triglycerides and the cholesterol concentrations in plasma and liver were not different between the two groups of rats. Livers of glutathione-deficient rats had lower mRNA abundance of sterol regulatory element-binding protein (SREBP)-1c (-47%), Spot (S)14 (-29%) and diacylglycerol acyltransferase 2 (DGAT-2, -27%) and a lower enzyme activity of fatty acid synthase (FAS, -26%) than livers of the control rats. Glutathione-deficient rats had also a lower hepatic activity of the redox-sensitive protein-tyrosine phosphatase (PTP)1B, and a higher concentration of irreversible oxidized PTP1B than control rats. No differences were observed in protein expression of total PTP1B and the mature mRNA encoding active XBP1s, a key regulator of unfolded protein and ER stress response. Conclusion This study shows that glutathione deficiency lowers hepatic triglyceride concentrations via influencing lipogenesis. The reduced activity of PTP1B and the higher concentration of irreversible oxidized PTP1B could be, at least in part, responsible for this effect. PMID:20482862

  17. Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats

    PubMed Central

    Kanter, Mehmet; Demir, Halit; Karakaya, Cengiz; Ozbek, Hanefi

    2005-01-01

    AIM: To evaluate the role of reactive oxygen species in the pathogenesis of acute ethanol-induced gastric mucosal lesions and the effect of Nigella sativa L oil (NS) and its constituent thymoquinone (TQ) in an exper-imental model. METHODS: Male Wistar albino rats were assigned into 4 groups. Control group was given physiologic saline orally (10 mL/kg body weight) as the vehicle (gavage); ethanol group was administrated 1 mL (per rat) absolute alcohol by gavage; the third and fourth groups were given NS (10 mL/kg body weight) and TQ (10 mg/kg body weight p.o) respectively 1 h prior to alcohol intake. One hour after ethanol administration, stomach tissues were excised for macroscopic examination and biochemical analysis. RESULTS: NS and TQ could protect gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index (UI) values. NS prevented alcohol-induced increase in thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation. NS also increased gastric glutathione content (GSH), enzymatic activities of gastric superoxide dismutase (SOD) and glutathione-S-transferase (GST). Likewise, TQ protected against the ulcerating effect of alcohol and mitigated most of the biochemical adverse effects induced by alcohol in gastric mucosa, but to a lesser extent than NS. Neither NS nor TQ affected catalase activity in gastric tissue. CONCLUSION: Both NS and TQ, particularly NS can partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects might be induced, at least partly by their radical scavenging activity. PMID:16425361

  18. The efficacy of sucralfate suspension in the prevention of oral mucositis due to radiation therapy

    SciTech Connect

    Epstein, J.B.; Wong, F.L.W. (British Columbia Cancer Agency, Vancouver (Canada))

    1994-02-01

    The purpose of this study was to assess the value of sucralfate suspension in prevention of oral mucositis and for reduction of oral pain in patients who develop mucositis during radiation therapy. The study was a double-blind, placebo-controlled, randomized prospective trial of a sucralfate suspension in the prevention and management of oral mucositis during radiation therapy. Oral mucositis was assessed using a quantitative scale and symptoms were assessed using visual analogue scales. The statistical model was developed to detect a 40% reduction in mucositis. No statistically significant reduction in mucositis was seen. Early during radiation therapy less oral pain was reported in the sucralfate group, but as treatment progressed all patients experienced pain. Patients in the sucralfate group were prescribed topical and systemic analgesics later in the course of radiation therapy. Prophylactic oral rinsing with sucralfate did not prevent oral ulcerative mucositis. Sucralfate may reduce the experience of pain during radiation therapy. 32 refs., 3 tabs.

  19. Oral Doxepin Rinse: The Analgesic Effect and Duration of Pain Reduction in Patients with Oral Mucositis Due to Cancer Therapy

    Microsoft Academic Search

    Joel B. Epstein; Joshua D. Epstein; Matthew S. Epstein; Hal Oien; Edmond L. Truelove

    2006-01-01

    This research expands on our prior study, in which we assessed pain reduction after topical doxepin rinse in patients with oral mucositis resulting from cancer and cancer therapy. We continued to enroll patients with painful oral mucositis attributable solely to cancer therapy and performed further analysis on the duration of pain reduction. Fifty-one patients with oral mucositis were enrolled. Mucositis

  20. The effects of HIV infection on oral mucosal immunity.

    PubMed

    Challacombe, S J; Naglik, J R

    2006-01-01

    Oral mucosal infections, especially candidiasis, are a feature of HIV disease, suggesting that compromised mucosal immunity within the oral cavity is a consequence of the viral infection. However, how this mucosal immunity is compromised and at what stage of HIV infection this occurs are unclear. Better understanding of the protection of the oral cavity against infection has allowed us to gain some insight into the local consequences of HIV infection. From a humoral perpective, IgA2 subclasses are reduced in HIV infection in saliva, and total secretory IgA levels are reduced in later disease. Similarly, mucosal antibody responses appear near normal in early HIV infection but reduced in AIDS. There is now convincing evidence that salivary IgA can be neutralizing to HIV 1 and HIV 2, as well as block epithelial transmigration. Oral cellular immunity is also affected by HIV infection. Transmission of HIV from one oral cell type to another appears to be confirmed by work showing that HIV can bind to or infect epithelial cells, Langerhans cells, and other mucosal cells. CXCR4 tropic (via GalCer and CXCR4) and dual tropic HIV strains have been shown to be able to infect normal human oral keratinocytes (NHOKs), and infectious HIV virions can also be conveyed from NHOKs to activated peripheral blood lymphocytes, suggesting a potential role of oral epithelial cells in the transmission of HIV infection. There is evidence of up-regulation of various receptors, including HIV receptors, on the surface of oral epithelium, and the epithelium may become more permeable. HIV may exploit this antigen uptake mechanism to cross epithelial barriers during co-infection with damage-inducing pathogens such as Candida. Immune responsiveness to many of the co-pathogens associated with HIV has been demonstrated to depend on a family of innate recognition molecules, known as Toll-like receptors (TLR), and recognition of a single pathogen can involve activation of multiple TLRs. Consequently, TLR-pathogen interactions could play an indirect but major role in regulating HIV-associated disease in the oral cavity. Thus, HIV infection appears to have both direct and indirect effects on oral mucosal immunity, affecting both cellular and humoral immunity as well as both specific and innate immunity. PMID:16672546

  1. Hepatic glutathione and glutathione S-transferase in selenium deficiency and toxicity in the chick

    SciTech Connect

    Kim, Y. S.

    1989-01-01

    First, the hepatic activity of GSH-T{sub CDNB} was increased only under conditions of severe oxidative stress produced by combined Se- and vitamin E (VE)-deficiency, indicating that VE also affects GSH metabolism. Second, the incorporation of {sup 35}S-methionine into GSH and protein was about 4- and 2-fold higher, respectively, in Se- and VE-deficient chick hepatocytes as compared to controls. Third, chicks injected with the glutathione peroxidase (SeGSHpx) inhibitor, aurothioglucose (AuTG), showed increase hepatic GSH-T{sub CDNB} activity and plasma GSH concentration regardless of their Se status. Fourth, the effect of ascorbic acid (AA), on GSH metabolism was studied. Chicks fed 1000 ppm AA showed decreased hepatic GSH concentration compared to chicks fed no AA in a Se- and VE-deficient diet. Fifth, chicks fed excess Se showed increase hepatic activity of GSH-T{sub CDNB} and GSH concentration regardless of VE status.

  2. Effect of cobalt on biliary excretion of bilirubin and glutathione

    SciTech Connect

    Stelzer, K.J.; Klaassen, C.D.

    1985-01-01

    Adult male rats received cobaltous chloride (250 mol/kg, sc) at various times (1-72 h) prior to assessment of hepatic heme oxygenase activity, bile flow, biliary concentration of bilirubin-glucuronides, and hepatic and biliary glutathione concentrations. Hepatic heme oxygenase activity increased 360% 24 h after treatment but returned to control levels by 72 h. Total biliary concentrations of the mono- and diglucuronides of bilirubin (BMG and BDG) were increased 47% at 24 h and returned to control levels more slowly than did heme oxygenase. Bile flow was not significantly changed at any time. Concentrations of hepatic reduced and oxidized glutathione (GSH and GSSG) tended to increase after cobalt, but changes were not statistically significant. Biliary GSH and GSSG increased 1 h after cobalt treatment and were twice control values 3 h after treatment. These biliary glutathione concentrations declined to the control range by 6 h. These results demonstrate that increased liver heme oxygenase activity following cobalt treatment may be associated with elevated biliary excretion of bilirubin glucuronides. However, changes that occurred in biliary excretion of glutathione in response to cobalt treatment were not accompanied by parallel changes in hepatic glutathione levels.

  3. Glutathione is required for efficient production of infectious picornavirus virions

    SciTech Connect

    Smith, Allen D. [Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705 (United States)]. E-mail: smitha@ba.ars.usda.gov; Dawson, Harry [Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705 (United States)]. E-mail: dawsonh@ba.ars.usda.gov

    2006-09-30

    Glutathione is an intracellular reducing agent that helps maintain the redox potential of the cell and is important for immune function. The drug L-buthionine sulfoximine (BSO) selectively inhibits glutathione synthesis. Glutathione has been reported to block replication of HIV, HSV-1, and influenza virus, whereas cells treated with BSO exhibit increased replication of Sendai virus. Pre-treatment of HeLa cell monolayers with BSO inhibited replication of CVB3, CVB4, and HRV14 with viral titers reduced by approximately 6, 5, and 3 log{sub 1}, respectively. The addition of glutathione ethyl ester, but not dithiothreitol or 2-mercaptoethanol, to the culture medium reversed the inhibitory effect of BSO. Viral RNA and protein synthesis were not inhibited by BSO treatment. Fractionation of lysates from CVB3-infected BSO-treated cells on cesium chloride and sucrose gradients revealed that empty capsids but not mature virions were being produced. The levels of the 5S and 14S assembly intermediates, however, were not affected by BSO treatment. These results demonstrate that glutathione is important for production of mature infectious picornavirus virions.

  4. Lung lining fluid glutathione attenuates IL-13-induced asthma.

    PubMed

    Lowry, Matthew H; McAllister, Brian P; Jean, Jyh-Chang; Brown, Lou Ann S; Hughey, Rebecca P; Cruikshank, William W; Amar, Sal; Lucey, Edgar C; Braun, Kathleen; Johnson, Pamela; Wight, Thomas N; Joyce-Brady, Martin

    2008-05-01

    GGT(enu1) mice, deficient in gamma-glutamyl transferase and unable to metabolize extracellular glutathione, develop intracellular glutathione deficiency and oxidant stress. We used intratracheal IL-13 to induce airway inflammation and asthma in wild-type (WT) and GGT(enu1) mice to determine the effect of altered glutathione metabolism on bronchial asthma. WT and GGT(enu1) mice developed similar degrees of lung inflammation. In contrast, IL-13 induced airway epithelial cell mucous cell hyperplasia, mucin and mucin-related gene expression, epidermal growth factor receptor mRNA, and epidermal growth factor receptor activation along with airway hyperreactivity in WT mice but not in GGT(enu1) mice. Lung lining fluid (extracellular) glutathione was 10-fold greater in GGT(enu1) than in WT lungs, providing increased buffering of inflammation-associated reactive oxygen species. Pharmacologic inhibition of GGT in WT mice produced similar effects, suggesting that the lung lining fluid glutathione protects against epithelial cell induction of asthma. Inhibiting GGT activity in lung lining fluid may represent a novel therapeutic approach for preventing and treating asthma. PMID:18063838

  5. Radical cystectomy and pelvic lymphadenectomy with ileal conduit urinary diversion and abdominal wall reconstruction: an interesting case of multidisciplinary management

    PubMed Central

    Sofos, Stratos S; Walsh, Ciaran J; Parr, Nigel J; Hancock, Kevin

    2015-01-01

    The ileal conduit for urinary diversion after radical cystectomy is a well-described procedure. Furthermore, parastomal hernias, prolapse, stenosis, and retraction of the stoma have been reported as some of the more common complications of this procedure. The subsequent repair of parastomal hernias with a biological mesh and the potential of the conduit to “tunnel” through it has also been described. In this case report, we present a combined repair of a large incisional hernia with a cystectomy and a pelvic lymphadenectomy for invasive bladder cancer, with the use of a biological mesh for posterior component abdominal wall primary repair as well as for support to the ileal conduit used for urinary diversion. PMID:25653561

  6. [A case of percutaneous BCG perfusion therapy for CIS of upper urinary tract CIS after radical cystectomy with ileal neobladder].

    PubMed

    Obayashi, Koki; Miki, Jun; Kasai, Kanako; Tashiro, Kojiro; Tsuduki, Shunsuke; Bando, Shigehiro; Ishii, Gen; Suzuki, Kan; Kimura, Takahiro; Kishimoto, Koichiro; Egawa, Sin

    2014-09-01

    We report a case of percutaneous bacillus Calmette-Guérin (BCG) perfusion therapy for carcinoma in situ (CIS) of upper urinary tract after radical cystectomy with ileal neobladder. A 42-year-old man underwent radical cystectomy and ileal neobladder diversion due to the recurrence of CIS in prostatic urethra after transurethral resection of bladder tumor 3 times and 2 courses of intravesical BCG therapy. Final pathological findings showed the presence of CIS in the right distal ureteral margin. After the radical cystectomy, our diagnosis was CIS in the right residual ureter, because of positive urine cytology and negative radiographic findings in the upper urinary tract. We performed the percutaneous BCG perfusion therapy for CIS of the right upper urinary tract after the construction of the percutaneous nephrostomy by intentionally inducing hydronephrosis. No recurrence was found after 3 years of BCG perfusion therapy. PMID:25293799

  7. Hepatic pseudocystic metastasis of well-differentiated ileal neuroendocrine tumor: a case report with review of the literature

    PubMed Central

    2013-01-01

    Abstract Imaging appearance of cyst-like changes is most frequently described in primary neuroendocrine lesions, especially pancreatic NETs. The imaging finding of a pseudocystic lesion of the liver puts in differential diagnosis many pathologies such as infectious diseases, simple biliary cysts up to biliary cystadenomas and eventually to primary or metastatic malignancies. Primary or metastatic hepatic malignancies with pseudocystic aspects are rare, and a pseudocystic aspect is reported only after neo-adjuvant treatment. Liver metastasis of untreated neuroendocrine tumors are usually solid and, to our knowledge, only two cases of neuroendocrine cystic hepatic metastases of ileal atypical carcinoids have been reported so far. We present a case of a 67 years old man with synchronous finding of an untreated hepatic pseudocystic lesion and an ileal mass histologically diagnosed as a well differentiated (G1) neuroendocrine tumor. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1443883503102967. PMID:24034980

  8. Evidence That Glutathione and the Glutathione System Efficiently Recycle 1-Cys Sulfiredoxin In Vivo

    PubMed Central

    Boukhenouna, Samia; Mazon, Hortense; Branlant, Guy; Jacob, Christophe; Toledano, Michel B.

    2015-01-01

    Abstract Aims: Typical 2-Cys peroxiredoxins (2-Cys Prxs) are Cys peroxidases that undergo inactivation by hyperoxidation of the catalytic Cys, a modification reversed by ATP-dependent reduction by sulfiredoxin (Srx). Such an attribute is thought to provide regulation of 2-Cys Prxs functions. The initial steps of the Srx catalytic mechanism lead to a Prx/Srx thiolsulfinate intermediate that must be reduced to regenerate Srx. In Saccharomyces cerevisiae Srx, the thiolsulfinate is resolved by an extra Cys (Cys48) that is absent in mammalian, plant, and cyanobacteria Srxs (1-Cys Srxs). We have addressed the mechanism of reduction of 1-Cys Srxs using S. cerevisiae Srx mutants lacking Cys48 as a model. Results: We have tested the recycling of Srx by glutathione (GSH) by a combination of in vitro steady-state and single-turnover kinetic analyses, using enzymatic coupled assays, Prx fluorescence, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and reverse-phase chromatography coupled to mass spectrometry. We demonstrate that GSH reacts directly with the thiolsulfinate intermediate, by following saturation kinetics with an apparent dissociation constant of 34??M, while producing S-glutathionylated Srx as a catalytic intermediate which is efficiently reduced by the glutaredoxin/glutathione reductase system. Total cellular depletion of GSH impacted the recycling of Srx, confirming in vivo that GSH is the physiologic reducer of 1-Cys Srx. Innovation: Our study suggests that GSH binds to the thiolsulfinate complex, thus allowing non-rate limiting reduction. Such a structural recognition of GSH enables an efficient catalytic reduction, even at very low GSH cellular levels. Conclusion: This study provides both in vitro and in vivo evidence of the role of GSH as the primary reducer of 1-Cys Srxs. Antioxid. Redox Signal. 22, 731–743. PMID:25387359

  9. Dietary supplementation with Chinese herbal powder enhances ileal digestibilities and serum concentrations of amino acids in young pigs

    Microsoft Academic Search

    X. F. Kong; Y. L. Yin; Q. H. He; F. G. Yin; H. J. Liu; T. J. Li; R. L. Huang; M. M. Geng; Z. Ruan; Z. Y. Deng; M. Y. Xie; G. Wu

    2009-01-01

    This study was designed to determine the effect of ultra-fine Chinese herbal powder as a dietary additive on serum concentrations\\u000a and apparent ileal digestibilities (AID) of amino acids (AA) in young pigs. In Experiment 1, 60 Duroc × Landrace × Yorkshire\\u000a piglets weaned at 21 days of age were randomly assigned to one of three treatments, representing supplementation with 0 or\\u000a 2 g\\/kg of the powder,

  10. Dietary supplementation with Astragalus polysaccharide enhances ileal digestibilities and serum concentrations of amino acids in early weaned piglets

    Microsoft Academic Search

    F. G. Yin; Y. L. Liu; Y. L. Yin; X. F. Kong; R. L. Huang; T. J. Li; G. Y. Wu; Yongqing Hou

    2009-01-01

    Two experiments were conducted to evaluate the effects of dietary supplementation with Astragalus polysaccharide (APS) on growth performance, apparent ileal digestibilities (AID) of amino acids (AA), and their serum concentrations\\u000a in early weaned piglets. In Exp. 1, 60 pigs were weaned at 21 days of age (BW 7.35 ± 0.23 kg) and allocated to three treatments\\u000a (20 pigs\\/treatment), representing supplementing 0.0% (control), 0.02% colistin

  11. Surgical Treatment of Morbid Obesity: Midterm Outcomes of the Laparoscopic Ileal Interposition Associated to a Sleeve Gastrectomy in 120 Patients

    Microsoft Academic Search

    Aureo L. DePaula; Alessandro R. Stival; Alfredo Halpern; Sergio Vencio

    2011-01-01

    The aim of this study was to evaluate the mid-term outcomes of the laparoscopic ileal interposition associated to a sleeve\\u000a gastrectomy (LII-SG) for the treatment of morbid obesity. The procedure was performed in 120 patients: 71 women and 49 men\\u000a with mean age of 41.4 years. Mean body mass index (BMI) was 43.4?±?4.2 kg\\/m2. Patients had to meet requirements of the 1991

  12. Potential of SeHCAT retention as an indicator of terminal ileal involvement in inflammatory bowel disease

    Microsoft Academic Search

    G. Holdstock; G. Phillips; T. K. Hames; B. R. Condon; J. S. Fleming; C. L. Smith; D. M. Ackery

    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

  13. Assessment of ileal function by abdominal counting of the retention of a gamma emitting bile acid analogue

    Microsoft Academic Search

    E H Thaysen; M Orholm; T Arnfred; J Carl; P Rødbro

    1982-01-01

    In eight patients without gastrointestinal complaints and 30 patients with various gastrointestinal disorders ileal bile acid conservation was assessed by oral administration of 75Se 23-selena-25-homocholic acid (SeHCAT) followed by abdominal gamma counting (SeHCAT-test). The results of the test correlated fairly well with the clinical features and with the [1-14C]-cholylglycine breath test including faecal 14C measurements (breath test). Of the two

  14. Beneficial effects of Camellia Oil (Camellia oleifera Abel.) on ketoprofen-induced gastrointestinal mucosal damage through upregulation of HO-1 and VEGF.

    PubMed

    Cheng, Yu-Ting; Wu, Shu-Li; Ho, Cheng-Ying; Huang, Shang-Ming; Cheng, Chun-Lung; Yen, Gow-Chin

    2014-01-22

    Nonsteroidal anti-inflammatory drugs, such as ketoprofen, are generally used to treat pain and inflammation and as pyretic agents in clinical medicine. However, the usage of these drugs may lead to oxidative injury to the gastrointestinal mucosa. Camellia oil ( Camellia oleifera Abel.) is commonly used in Taiwan and China as cooking oil. Traditional remedies containing this oil exert beneficial health effects on the bowel, stomach, liver, and lungs. However, the effects of camellia oil on ketoprofen-induced oxidative gastrointestinal mucosal lesions remain unknown. The objective of this study was to evaluate the effect of camellia oil on ketoprofen-induced acute gastrointestinal ulcers. The results showed that treatment of Int-407 cells with camellia oil (50-75 ?g/mL) not only increased the levels of heme oxygenase-1 (HO-1), glutathione peroxidase (GPx), and superoxide dismutase (SOD) mRNA expression but also increased vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) protein secretion, which served as a mucosal barrier against gastrointestinal oxidative injury. Moreover, Sprague-Dawley (SD) rats treated with camellia oil (2 mL/kg/day) prior to the administration of ketoprofen (50 mg/kg/day) successfully inhibited COX-2 protein expression, inhibited the production of interleukin-6 (IL-6) and nitrite oxide (NO), reversed the impairment of the antioxidant system, and decreased oxidative damage in the gastrointestinal mucosa. More importantly, pretreatment of SD rats with camellia oil strongly inhibited gastrointestinal mucosal injury induced by ketoprofen, which was proved by the histopathological staining of gastrointestinal tissues. Our data suggest that camellia oil exerts potent antiulcer effects against oxidative damage in the stomach and intestine induced by ketoprofen. PMID:24377395

  15. Interaction between Ca/sup + +/-channel antagonists and. cap alpha. /sub 2/-adrenergic receptors in rabbit ileal cell membrane

    SciTech Connect

    Homeidan, F.R.; Wicks, J.; Cusolito, S.; El-Sabban, M.E.; Sharp, G.W.G.; Donowitz, M.

    1986-03-05

    An interaction between Ca/sup + +/-channel antagonists and the ..cap alpha../sub 2/-adrenergic receptor on active electrolyte transport was demonstrated in rabbit ileum. Clonidine, an ..cap alpha../sub 2/-agonist, stimulated NaCl absorption apparently by Ca/sup + +/-channel antagonism since it inhibited /sup 45/Ca/sup + +/ uptake across the basolateral membrane and decreased total ileal calcium content. This stimulation was inhibited by the Ca/sup + +/-channel antagonists dl- and l-verapamil and cadmium but not by nifedipine. The binding of /sup 3/H-yohimbine, a specific ..cap alpha../sub 2/-adrenergic antagonist, was studied on purified ileal cell membranes using a rapid filtration technique. dl-Verapamil and Cd/sup + +/ inhibited the specific binding of /sup 3/H-yohimbine over the same concentration range in which they affected transport. In contrast, nifedipine had no effect on binding, just as it had no effect on clonidine-stimulated NaCl absorption. These data demonstrate that there is an interaction between Ca/sup + +/-channels and ..cap alpha../sub 2/-adrenergic receptors in ileal basolateral membranes. Some Ca/sup + +/-channel antagonists alter ..cap alpha../sub 2/-adrenergic binding to the receptor and ..cap alpha../sub 2/-agonist binding leads to changes in Ca/sup + +/ entry. A close spatial relationship between the Ca/sup + +/-channel and the ..cap alpha../sub 2/-receptor could explain the data.

  16. CGRP upregulation in dorsal root ganglia and ileal mucosa during Clostridium difficile toxin A-induced enteritis.

    PubMed

    Keates, A C; Castagliuolo, I; Qiu, B; Nikulasson, S; Sengupta, A; Pothoulakis, C

    1998-01-01

    We have previously reported that pretreatment of rats with capsaicin (an agent that ablates sensory neurons) or CP-96345 (a substance P receptor antagonist) dramatically inhibits fluid secretion and intestinal inflammation in ileal loops exposed to Clostridium difficile toxin A. The aim of this study was to determine whether calcitonin gene-related peptide (CGRP), a neuropeptide also found in sensory afferent neurons, participates in the enterotoxic effects of toxin A. Administration of toxin A was also found to increase CGRP content in dorsal root ganglia and ileal mucosa 60 min after toxin exposure. Furthermore, immunohistochemical studies demonstrated increased neuronal staining for CGRP 2 h after toxin A treatment. Pretreatment of rats with CGRP-(8-37), a specific CGRP antagonist, before instillation of toxin A into ileal loops significantly inhibited toxin-mediated fluid secretion (by 48%), mannitol permeability (by 83%), and histological damage. We conclude that CGRP, like substance P, contributes to the secretory and inflammatory effects of toxin A via increased production of this peptide from intestinal nerves, including primary sensory afferent neurons. PMID:9458790

  17. Microbiota: host interactions in mucosal homeostasis and systemic autoimmunity.

    PubMed

    Longman, Randy S; Yang, Yi; Diehl, Gretchen E; Kim, Sangwon V; Littman, Dan R

    2013-01-01

    The vertebrate intestinal tract is colonized by hundreds of species of bacteria that must be compartmentalized and tolerated to prevent invasive growth and harmful inflammatory responses. Signaling initiated by commensal bacteria shapes antigen-specific mucosal and systemic adaptive immunity. A distinct type of effector CD4(+) T cells, Th17 cells, have a key role in coordinating the inflammatory immune responses that afford protection to pathogens at the mucosal interface. Balancing this powerful inflammatory response, regulatory T cells limit collateral damage and provide antigen-specific tolerance to both food and microbial antigens. Here, we discuss the implications for how the microbiota as a whole contributes to compartmentalization from the host and how individual constituents of the microbiota influence the functions and repertoire of effector T cells and organ-specific autoimmune disease. PMID:24913313

  18. Microbiota-Host Interactions in Mucosal Homeostasis and Systemic Autoimmunity

    PubMed Central

    Longman, Randy S.; Yang, Yi; Diehl, Gretchen E.; Kim, Sangwon V.; Littman, Dan R.

    2015-01-01

    The vertebrate intestinal tract is colonized by hundreds of species of bacteria that must be compartmentalized and tolerated to prevent invasive growth and harmful inflammatory responses. Signaling initiated by commensal bacteria shapes antigen-specific mucosal and systemic adaptive immunity. A distinct type of effector CD4+ T cells, Th17 cells, play a key role in coordinating the inflammatory immune responses that afford protection to pathogens at the mucosal interface. Balancing this powerful inflammatory response, regulatory T cells limit collateral damage and provide antigen-specific tolerance to both food and microbial antigens. Here, we discuss the implications for how the microbiota as a whole contribute to compartmentalization from the host and how individual constituents of the microbiota influence the functions and repertoire of effector T cells and organ-specific autoimmune disease. PMID:24913313

  19. Mucosal Immunity in the Female Genital Tract, HIV/AIDS

    PubMed Central

    Reis Machado, Juliana; da Silva, Marcos Vinícius; Cavellani, Camila Lourencini; Antônia dos Reis, Marlene; Monteiro, Maria Luiza Gonçalves dos Reis; Teixeira, Vicente de Paula Antunes; Rosa Miranda Corrêa, Rosana

    2014-01-01

    Mucosal immunity consists of innate and adaptive immune responses which can be influenced by systemic immunity. Despite having been the subject of intensive studies, it is not fully elucidated what exactly occurs after HIV contact with the female genital tract mucosa. The sexual route is the main route of HIV transmission, with an increased risk of infection in women compared to men. Several characteristics of the female genital tract make it suitable for inoculation, establishment of infection, and systemic spread of the virus, which causes local changes that may favor the development of infections by other pathogens, often called sexually transmitted diseases (STDs). The relationship of these STDs with HIV infection has been widely studied. Here we review the characteristics of mucosal immunity of the female genital tract, its alterations due to HIV/AIDS, and the characteristics of coinfections between HIV/AIDS and the most prevalent STDs. PMID:25313360

  20. Prevalence of Oral Mucosal Lesions in Male Smokers and Nonsmokers

    PubMed Central

    Ahmadi-Motamayel, Fatemeh; Falsafi, Parisa; Hayati, Zahra; Rezaei, Farzad

    2013-01-01

    Tobacco smoking is one of the most important risk factors for the development of oral mucosal lesions such as leukoplakia and hairy tongue. Controversy exists in the literature, however, about the prevalence of oral lesions in smokers. The aim of this study was to evaluate oral lesions in male smokers compared with nonsmokers in Hamadan. A total of 516 male participants were assessed, 258 of whom were smokers and 258 of whom were healthy nonsmokers. The prevalence of lesions was evaluated by clinical observation and biopsy. We found that the most prevalent lesions among smokers were gingival problems and coated tongue; smokers had significantly more lesions than did nonsmokers. Malignant and premalignant lesions were found in a higher age range. Among all participants in our study, we found a large number of oral mucosal lesions in smokers that had a strong correlation with smoking. Dental services need to implement care and health education for smokers to promote health. PMID:24010068

  1. Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions

    PubMed Central

    Lushchak, Volodymyr I.

    2012-01-01

    Glutathione (GSH) is a tripeptide, which has many biological roles including protection against reactive oxygen and nitrogen species. The primary goal of this paper is to characterize the principal mechanisms of the protective role of GSH against reactive species and electrophiles. The ancillary goals are to provide up-to-date knowledge of GSH biosynthesis, hydrolysis, and utilization; intracellular compartmentalization and interorgan transfer; elimination of endogenously produced toxicants; involvement in metal homeostasis; glutathione-related enzymes and their regulation; glutathionylation of sulfhydryls. Individual sections are devoted to the relationships between GSH homeostasis and pathologies as well as to developed research tools and pharmacological approaches to manipulating GSH levels. Special attention is paid to compounds mainly of a natural origin (phytochemicals) which affect GSH-related processes. The paper provides starting points for development of novel tools and provides a hypothesis for investigation of the physiology and biochemistry of glutathione with a focus on human and animal health. PMID:22500213

  2. Hemolytic anemia and metabolic acidosis: think about glutathione synthetase deficiency.

    PubMed

    Ben Ameur, Salma; Aloulou, Hajer; Nasrallah, Fehmi; Kamoun, Thouraya; Kaabachi, Naziha; Hachicha, Mongia

    2015-02-01

    Glutathione synthetase deficiency (GSSD) is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with hemolytic anemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low glutathione synthetase activity in erythrocytes or cultured skin fibroblasts. The prognosis seems to depend on early diagnosis and treatment. We report a 4 months old Tunisian male infant who presented with severe metabolic acidosis with high anion gap and hemolytic anemia. High level of 5-oxoproline was detected in her urine and diagnosis of GSSD was made. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. He died of severe metabolic acidosis and sepsis at the age of 15 months. PMID:25166299

  3. Elevation of Glutathione as a Therapeutic Strategy in Alzheimer Disease

    PubMed Central

    Pocernich, Chava B.; Butterfield, D. Allan

    2011-01-01

    Oxidative stress has been associated with the onset and progression of mild cognitive impairment (MCI) and Alzheimer disease (AD). AD and MCI brain and plasma display extensive oxidative stress as indexed by protein oxidation, lipid peroxidation, free radical formation, DNA oxidation, and decreased antioxidants. The most abundant endogenous antioxidant, glutathione, plays a significant role in combating oxidative stress. The ratio of oxidized to reduced glutathione is utilized as a measure of intensity of oxidative stress. Antioxidants have long been considered as an approach to slow down AD progression. In this review, we focus on the elevation on glutathione through N-acytl-cysteine (NAC) and ?-glutamylcysteine ethyl ester (GCEE) as a potential therapeutic approach for Alzheimer disease. PMID:22015471

  4. What interactions drive the salivary mucosal pellicle formation?

    PubMed

    Gibbins, Hannah L; Yakubov, Gleb E; Proctor, Gordon B; Wilson, Stephen; Carpenter, Guy H

    2014-08-01

    The bound salivary pellicle is essential for protection of both the enamel and mucosa in the oral cavity. The enamel pellicle formation is well characterised, however the mucosal pellicle proteins have only recently been clarified and what drives their formation is still unclear. The aim of this study was to examine the salivary pellicle on particles with different surface properties (hydrophobic or hydrophilic with a positive or negative charge), to determine a suitable model to mimic the mucosal pellicle. A secondary aim was to use the model to test how transglutaminase may alter pellicle formation. Particles were incubated with resting whole mouth saliva, parotid saliva and submandibular/sublingual saliva. Following incubation and two PBS and water washes bound salivary proteins were eluted with two concentrations of SDS, which were later analysed using SDS-PAGE and Western blotting. Experiments were repeated with purified transglutaminase to determine how this epithelial-derived enzyme may alter the bound pellicle. Protein pellicles varied according to the starting salivary composition and the particle chemistry. Amylase, the single most abundant protein in saliva, did not bind to any particle indicating specific protein binding. Most proteins bound through hydrophobic interactions and a few according to their charges. The hydrophobic surface most closely matched the known salivary mucosal pellicle by containing mucins, cystatin and statherin but an absence of amylase and proline-rich proteins. This surface was further used to examine the effect of added transglutaminase. At the concentrations used only statherin showed any evidence of crosslinking with itself or another saliva protein. In conclusion, the formation of the salivary mucosal pellicle is probably mediated, at least in part, by hydrophobic interactions to the epithelial cell surface. PMID:24921197

  5. Induction of Allergen-Specific Tolerance via Mucosal Routes

    Microsoft Academic Search

    Laurent Mascarell; Aline Zimmer; Laurence Van Overtvelt; Sophie Tourdot; Philippe Moingeon

    \\u000a Allergen-specific immunotherapy is the only curative treatment of allergies against insect venom, house dust mites, tree\\/grass\\u000a pollens, or cat dander. Subcutaneous immunotherapy is successful to reorient the immune system and re-establish long-term\\u000a tolerance. However, major drawbacks for using this route include: repeated injections, as well as the risk of anaphylaxis.\\u000a In this context, alternative mucosal routes of administration are being

  6. Normal flora and mucosal immunity of the head and neck.

    PubMed

    Roscoe, D L; Chow, A W

    1988-03-01

    The study of the human resident flora has grown from Antony van Leeuwenhoek's simple descriptions some 300 years ago to the sophisticated investigations being done today. The acquisition of organisms and the subsequent course of either stable colonization or invasion of the host involve complex host-parasite interactions. From one perspective, clearly host factors are operative that appear to select against certain species while being permissive for others. From another perspective, microbial species that are successful at colonization must overcome certain host factors to maintain a selective advantage and flourish within a particular body habitat. It is intriguing that whereas host mucosal defenses are a significant influence contributing to selection of the resident flora, it is this established flora that provides the host with perhaps its most important local defense system. In the head and neck areas, many of these mucosal surfaces are contiguous and thus for the most part share a common resident flora. These organisms are rarely involved in infection unless some breach of the mucosal surface or some upset in the balance of the normal flora occurs. On these occasions, the host is susceptible to infection from both newly acquired organisms and those previously present, which may now become invasive. In any event, it is clear that improved knowledge of the normal flora of the head and neck is essential for understanding and for effective treatment of infectious processes in this area. It is hoped that a better appreciation of the important role of the normal flora in maintaining the host mucosal defenses will further focus our attention on its preservation. PMID:3074102

  7. Ex vivo development of a composite human oral mucosal equivalent

    Microsoft Academic Search

    Kenji Izumi; Gyula Takacs; Hiroto Terashi; Stephen E Feinberg

    1999-01-01

    Purpose: The aim of this study was the ex vivo development of a composite oral mucosal equivalent composed of a continuous stratified layer of human oral keratinocytes grown on a cadaveric human dermal matrix in a defined medium without a feeder layer.Materials and Methods: Enzymatically dissociated human oral keratinocytes from keratinized oral mucosa were cultured, submerged in a serum-free, low-calcium

  8. Mucosal Kaposi sarcoma, a Rare Cancer Network study.

    PubMed

    Thariat, Juliette; Kirova, Youlia; Sio, Terence; Choussy, Olivier; Vees, Hans; Schick, Ulrich; Poissonnet, Gilles; Saada, Esma; Thyss, Antoine; Miller, Robert C

    2012-10-10

    Kaposi's sarcoma (KS) most often affect the skin but occasionally affect the mucosa of different anatomic sites. The management of mucosal KS is seldom described in the literature. Data from 15 eligible patients with mucosal KS treated between 1994 and 2008 in five institutions within three countries of the Rare Cancer Network group were collected. The inclusion criteria were as follows: age >16 years, confirmed pathological diagnosis, mucosal stages I and II, and a minimum of 6 months' follow-up after treatment. Head and neck sites were the most common (66%). Eleven cases were HIV-positive. CD4 counts correlated with disease stage. Twelve patients had biopsy only while three patients underwent local resection. Radiotherapy (RT) was delivered whatever their CD4 status was. Median total radiation dose was 16.2 Gy (0-45) delivered in median 17 days (0-40) with four patients receiving no RT. Six patients underwent chemotherapy and received from 1 to 11 cycles of various regimens namely vinblastin, caelyx, bleomycine, or interferon, whatever their CD4 counts was. Five-year disease free survival were 81.6% and 75.0% in patients undergoing RT or not, respectively. Median survival was 66.9 months. Radiation-induced toxicity was at worse grade 1-2 and was manageable whatever patients' HIV status. This small series of mucosal KSs revealed that relatively low-dose RT is overall safe and efficient in HIV-positive and negative patients. Since there are distant relapses either in multicentric cutaneous or visceral forms in head and neck cases, the role of systemic treatments may be worth investigations in addition to RT of localized disease. Surgery may be used for symptomatic lesions, with caution given the risk of bleeding. PMID:23372913

  9. Mucosal Kaposi sarcoma, a Rare Cancer Network study

    PubMed Central

    Thariat, Juliette; Kirova, Youlia; Sio, Terence; Choussy, Olivier; Vees, Hans; Schick, Ulrich; Poissonnet, Gilles; Saada, Esma; Thyss, Antoine; Miller, Robert C.

    2012-01-01

    Kaposi's sarcoma (KS) most often affect the skin but occasionally affect the mucosa of different anatomic sites. The management of mucosal KS is seldom described in the literature. Data from 15 eligible patients with mucosal KS treated between 1994 and 2008 in five institutions within three countries of the Rare Cancer Network group were collected. The inclusion criteria were as follows: age >16 years, confirmed pathological diagnosis, mucosal stages I and II, and a minimum of 6 months' follow-up after treatment. Head and neck sites were the most common (66%). Eleven cases were HIV-positive. CD4 counts correlated with disease stage. Twelve patients had biopsy only while three patients underwent local resection. Radiotherapy (RT) was delivered whatever their CD4 status was. Median total radiation dose was 16.2 Gy (0–45) delivered in median 17 days (0–40) with four patients receiving no RT. Six patients underwent chemotherapy and received from 1 to 11 cycles of various regimens namely vinblastin, caelyx, bleomycine, or interferon, whatever their CD4 counts was. Five-year disease free survival were 81.6% and 75.0% in patients undergoing RT or not, respectively. Median survival was 66.9 months. Radiation-induced toxicity was at worse grade 1–2 and was manageable whatever patients' HIV status. This small series of mucosal KSs revealed that relatively low-dose RT is overall safe and efficient in HIV-positive and negative patients. Since there are distant relapses either in multicentric cutaneous or visceral forms in head and neck cases, the role of systemic treatments may be worth investigations in addition to RT of localized disease. Surgery may be used for symptomatic lesions, with caution given the risk of bleeding. PMID:23372913

  10. Alterations of the mucosal immune system in inflammatory bowel disease

    Microsoft Academic Search

    Richard P. MacDermoit

    1996-01-01

    The normal intestinal immune system is under a balance in which proinflammatory and anti-inflammatory cells and molecules\\u000a are carefully regulated to promote a normal host mucosal defense capability without destruction of intestinal tissue. Once\\u000a this careful regulatory balance is disturbed, nonspecific stimulation and activation can lead to increased amounts of potent\\u000a destructive immunologic and inflammatory molecules being produced and released.

  11. Mucosal advancement in the treatment of anal fistula

    Microsoft Academic Search

    Pedro S. Aguilar; Gustavo Plasencia; Thomas G. Hardy; Rene F. Hartmann; William R. C. Stewart

    1985-01-01

    One hundred eighty-nine patients with anal fistula treated within an eight-month to seven-year period by anal fistulectomy\\u000a and rectal mucosal advancement are presented. An 80 percent follow-up revealed a 90 percent asymptomatic group and a ten percent\\u000a group who had minor symptoms. Eight percent of the symptomatic patients had minor soiling; 7 percent were incontinent for\\u000a gas, and 6 percent

  12. Intestinal epithelial cells and their role in innate mucosal immunity

    Microsoft Academic Search

    A. L. Maldonado-Contreras; Beth A. McCormick

    2011-01-01

    The mucosal surfaces of the respiratory, gastrointestinal and urogenital tracts are covered by a layer of epithelial cells\\u000a that are responsible for sensing and promoting a host immune response in order to establish the limits not only for commensal\\u000a microorganisms but also for foreign organisms or particles. This is a remarkable task as the human body represents a composite\\u000a of

  13. Metabolism of ethanol and carcinogens by glutathione transferases.

    PubMed Central

    Bora, P S; Spilburg, C A; Lange, L G

    1989-01-01

    Nonoxidative alcohol metabolism to form fatty acid ethyl esters contributes to alcohol-related end-organ damage, and these products are formed by two synthase enzymes. We recently purified the major (pI 4.9) synthase from human myocardium. The N-terminal sequence (A P Y T V V Y F P V R G R X K A L R M L X A D) is greater than 73% identical with that of a neutral (pI 6.7) detoxification enzyme, glutathione transferase P from rat hepatocellular carcinoma (P P Y T I V Y F P V R G R C E A T R M L L A D). Moreover, both the major human fatty acid ethyl ester synthase and bovine liver glutathione transferase catalyze the formation of fatty acid ethyl esters (Vmax 105 and 98 nmol per hr per mg, respectively). In addition, both enzymes catalyze the formation of glutathione-xenobiotic conjugates (Vmax 67 and 335 mol per hr per mol of enzyme, respectively). Physiological concentrations of glutathione increase the rate of formation of fatty acid ethyl esters up to 5-fold, and the glutathione transferase substrate 1-chloro-2,4-dinitrobenzene is a potent inhibitor of human myocardial fatty acid ethyl ester synthase. Thus, the identification of the major form of human myocardial fatty acid ethyl ester synthase as an acidic glutathione transferase links alcohol and xenobiotic metabolism and may relate the enhancement of tumorigenesis by alcohol abuse with carcinogen-conjugation reactions. PMID:2734299

  14. Assessment of red blood cell glutathione status in insulin resistance.

    PubMed

    Galgani, Jose E; Vasquez, Karla; Leonelli, Giannella; Espinosa, Alejandra; Araya, Hector; Perez-Bravo, Francisco

    2012-10-01

    The aim of this study was to assess red blood cell glutathione from insulin-sensitive and insulin-resistant individuals before and after an oral glucose dose. Fifteen healthy, young (24 ± 5 years), nonobese (23 ± 2 kg·m?²), insulin-sensitive (ISI composite = 6.0 ± 1.2) individuals and 14 healthy, young (22 ± 2 years), nonobese (24 ± 2 kg·m?²), insulin-resistant (ISI composite = 2.7 ± 1.1) individuals received a 75 g oral glucose dose. Blood samples were drawn before and for 2 h after glucose ingestion for red blood cell glutathione and serum glucose and insulin concentrations. Glycemia before and after glucose ingestion was similar between groups (p = 0.17), which suggest that hyperinsulinemia compensated impaired insulin sensitivity. Red blood cell total (p = 0.81), reduced (p = 0.79), and oxidized (p = 0.88) glutathione concentrations were similar between groups under fasting and postprandial conditions. However, in response to glucose, increases in total and reduced glutathione concentrations were found at the end of the 2 h assessment period in both groups (p < 0.05). Direct associations between postprandial glucose response and red blood cell total (r = 0.52; p < 0.05) and oxidized (r = 0.61; p = 0.02) glutathione concentrations were observed only in insulin-sensitive subjects. In conclusion, healthy individuals differing in their degree of insulin resistance showed similar red blood cell glutathione concentrations under non-glucose- and glucose-stimulated conditions. PMID:22871100

  15. Phytase Modulates Ileal Microbiota and Enhances Growth Performance of the Broiler Chickens

    PubMed Central

    Ptak, Anna; Bedford, Michael R.; ?wi?tkiewicz, Sylwester; ?y?a, Krzysztof; Józefiak, Damian

    2015-01-01

    Phytase is well studied and explored, however, little is known about its effects on the microbial ecology of the gastrointestinal tract. In total, 400 one-day-old female Ross 308 chicks were randomly distributed to four experimental groups. The dietary treatments were arranged as a 2 × 2 complete factorial design, with the factors being adequate (PC) or insufficient calcium (Ca) and digestible phosphor (dP)(NC) and with or without 5000 phytase units (FTU)/kg of Escherichia coli 6-phytase. The gastrointestinal tract pH values, ileal microbial communities and short-chain fatty acid concentrations in the digesta were determined. The reduction in Ca and dP concentration significantly affected pH in the crop and caeca, and addition of phytase to the NC resulted in a pH increase in the ileum. The reduction in Ca and dP concentration significantly lowered, while phytase supplementation increased ileal total bacterial counts. Additionally, the deficient diet reduced butyrate- but increased lactate-producing bacteria. The addition of phytase increased Lactobacillus sp./Enterococcus sp. whereas in case of Clostridium leptum subgroup, Clostridium coccoides - Eubacterium rectale cluster, Bifidobacterium sp. and Streptococcus/Lactococcus counts, a significant Ca and dP level x phytase interaction was found. However, the recorded interactions indicated that the effects of phytase and Ca and dP levels were not consistent. Furthermore, the reduction of Ca and dP level lowered Clostridium perfringens and Enterobacteriaceae counts. The analysis of fermentation products showed that reducing the Ca and dP content in the diet reduced total SCFA, DL-lactate, and acetic acid in the ileum whereas phytase increased concentrations of these acids in the NC group. This suggests that P is a factor which limits fermentation in the ileum. It may be concluded that phytase plays a role in modulating the gut microbiota of chicken, however, this is clearly linked with the levels of P and Ca in a diet. PMID:25781608

  16. Mucosal transmission and pathogenesis of chronic wasting disease in ferrets

    PubMed Central

    Perrott, Matthew R.; Sigurdson, Christina J.; Mason, Gary L.

    2013-01-01

    Chronic wasting disease (CWD) of cervids is almost certainly transmitted by mucosal contact with the causative prion, whether by direct (animal-to-animal) or indirect (environmental) means. Yet the sites and mechanisms of prion entry remain to be further understood. This study sought to extend this understanding by demonstrating that ferrets exposed to CWD via several mucosal routes developed infection, CWD prion protein (PrPCWD) amplification in lymphoid tissues, neural invasion and florid transmissible spongiform encephalopathy lesions resembling those in native cervid hosts. The ferrets developed extensive PrPCWD accumulation in the nervous system, retina and olfactory epithelium, with lesser deposition in tongue, muscle, salivary gland and the vomeronasal organ. PrPCWD accumulation in mucosal sites, including upper respiratory tract epithelium, olfactory epithelium and intestinal Peyer’s patches, make the shedding of prions by infected ferrets plausible. It was also observed that regionally targeted exposure of the nasopharyngeal mucosa resulted in an increased attack rate when compared with oral exposure. The latter finding suggests that nasal exposure enhances permissiveness to CWD infection. The ferret model has further potential for investigation of portals for initiation of CWD infection. PMID:23100363

  17. Cell-associated HIV mucosal transmission: the neglected pathway.

    PubMed

    Anderson, Deborah J; Le Grand, Roger

    2014-12-15

    This supplement to The Journal of Infectious Diseases is devoted to the important and understudied topic of cell-associated human immunodeficiency virus Type 1 (HIV) mucosal transmission. It stems from a workshop held in Boston, Massachusetts, in October 2013, in which scientists discussed their research and insights regarding cell-associated HIV mucosal transmission. The 10 articles in this supplement present the case for cell-associated HIV transmission as an important element contributing to the HIV epidemic, review evidence for the efficacy of current HIV prevention strategies against cell-associated HIV transmission and opportunities for further development, and describe in vitro, ex vivo, and animal cell-associated transmission models that can be used to further elucidate the molecular mechanisms of cell-associated HIV mucosal transmission and test HIV prevention strategies. We hope that these articles will help to inform and invigorate the HIV prevention field and contribute to the development of more-effective vaccine, treatment, and microbicide strategies for HIV prevention. PMID:25414413

  18. The mucosal expression pattern of interferon-? in rhesus macaques.

    PubMed

    Demers, Andrew; Kang, Guobin; Ma, Fungrui; Lu, Wuxun; Yuan, Zhe; Li, Yue; Lewis, Mark; Kraiselburd, Edmundo N; Montaner, Luis; Li, Qingsheng

    2014-12-01

    Type I IFNs play an important role in innate and adaptive immunity against viral infections. A novel type I IFN, namely IFN-?, which can protect against vaginal transmission of HSV2 and Chlamydia muridarum bacterial infection, has been described in mice and humans. Nevertheless, the principle cell type and the expression pattern of IFN-? in tissues remain uncertain. In addition, the expression of IFN-? in Indian rhesus macaques (Macaca mulatta) has not been reported. Here, we analyzed IFN-? expression in multiple mucosal sites of uninfected or SIV-infected Indian rhesus macaques using IHCS. We report for the first time the detection of IFN-? expression in situ in the lung, foreskin, vaginal, cervical, and small and large intestinal mucosae of rhesus macaques. We found that the expression of IFN-? was exclusive to the epithelial cells in all of the aforementioned mucosal tissues. Furthermore, the macaque IFN-? sequence in this study revealed that macaque IFN-? is highly conserved among human and other nonhuman primates. Lastly, SIV rectal infection did not significantly alter the expression of IFN-? in rectal mucosae. Together, these findings indicate that IFN-? may function as the first line of defense against the invasion of mucosal pathogens. Further studies should be conducted to examine IFN-? protection against gastrointestinal as well as respiratory infections. PMID:25139290

  19. Mucosal transmission and pathogenesis of chronic wasting disease in ferrets.

    PubMed

    Perrott, Matthew R; Sigurdson, Christina J; Mason, Gary L; Hoover, Edward A

    2013-02-01

    Chronic wasting disease (CWD) of cervids is almost certainly transmitted by mucosal contact with the causative prion, whether by direct (animal-to-animal) or indirect (environmental) means. Yet the sites and mechanisms of prion entry remain to be further understood. This study sought to extend this understanding by demonstrating that ferrets exposed to CWD via several mucosal routes developed infection, CWD prion protein (PrP(CWD)) amplification in lymphoid tissues, neural invasion and florid transmissible spongiform encephalopathy lesions resembling those in native cervid hosts. The ferrets developed extensive PrP(CWD) accumulation in the nervous system, retina and olfactory epithelium, with lesser deposition in tongue, muscle, salivary gland and the vomeronasal organ. PrP(CWD) accumulation in mucosal sites, including upper respiratory tract epithelium, olfactory epithelium and intestinal Peyer's patches, make the shedding of prions by infected ferrets plausible. It was also observed that regionally targeted exposure of the nasopharyngeal mucosa resulted in an increased attack rate when compared with oral exposure. The latter finding suggests that nasal exposure enhances permissiveness to CWD infection. The ferret model has further potential for investigation of portals for initiation of CWD infection. PMID:23100363

  20. Endoscopic ultrasonographic assessment of gastric polyps and endoscopic mucosal resection.

    PubMed

    Enestvedt, Brintha K; Chandrasekhara, Vinay; Ginsberg, Gregory G

    2012-12-01

    Gastric polyps refer to a heterogeneous group of epithelial- and subepithelial-based lesions that vary in histology and malignant potential. Although many gastric polyps have characteristic endoscopic appearances, their diagnosis, classification, and potential for malignant transformation are based on histologic evaluation. Therefore, all types of gastric polyps should be biopsied during the incident endoscopy. Mucosal-based polyps include fundic gland polyps, hyperplastic polyps, adenomatous polyps, and hamartomatous polyps. Inflammatory fibroid polyps may endoscopically appear similar to mucosal-based polyps but actually arise from the submucosa. Certain types of polyps are associated with genetic syndromes or potential precancerous conditions (gastric intestinal metaplasia and chronic atrophic gastritis). If dysplasia is present and the polyp is ?2 cm or symptomatic, the polyp should be endoscopically resected with the aim of en bloc resection. There are limited data on the use of adjunctive endoscopic ultrasound (EUS) in the evaluation of mucosal-based gastric polyps, and therefore, is not routinely employed in the management of these lesions. EUS is recommended for the evaluation of gastric subepithelial lesions. PMID:23001857

  1. Oral complications of cancer therapies. Management of mucositis during therapy

    SciTech Connect

    Miaskowski, C. (Univ. of California, San Francisco (USA))

    1990-01-01

    This paper reviews the purposes of an oral care protocol, the major components of an oral care regimen, and oral care protocols and studies done to date. Many questions remain in the area of optimal oral care for the patient experiencing mucositis as a sequela of cancer treatment. Research is needed on types and use of mouth rinses, effective, harmless, and pleasant lip lubricants, appropriate analgesic and anti-inflammatory combinations, and the effectiveness of a variety of devices for oral cleansing, to name a few areas. As outpatient oncology services grow, oral care protocols must be developed to meet the needs of ambulatory patient populations. Oral care regimens must be safe, easy to use, and economical as well as effective to ensure patient and staff compliance. Research on the management of mucositis must be conducted in both inpatient and outpatient settings. Finally, in order to obtain sufficient sample sizes and optimize data collection, these studies will need to be conducted by multidisciplinary teams (including dentists, oncologists, radiation therapists, and nurses) across multiple sites. Not until large-scale clinical trials are done on the treatment of mucositis will we be able to optimize the therapeutic regimen for the patient. 43 references.

  2. Aging and the mucosal immune system in the intestine.

    PubMed

    Mabbott, Neil A; Kobayashi, Atsushi; Sehgal, Anuj; Bradford, Barry M; Pattison, Mari; Donaldson, David S

    2015-04-01

    Bacterial and viral infections of the gastrointestinal tract are more common in the elderly and represent a major cause of morbidity and mortality. The mucosal immune system provides the first line of defence against pathogens acquired by ingestion and inhalation, but its function is adversely affected in the elderly. This aging-related decline in the immune function is termed immunosenescence and is associated with diminished abilities to generate protective immunity, reduced vaccine efficacy, increased incidence of cancer, inflammation and autoimmunity, and the impaired ability to generate tolerance to harmless antigens. In this review we describe our current understanding of the effects immunosenescence has on the innate and adaptive arms of the mucosal immune system in the intestine. Current estimates suggest that by the year 2050 up to 40 % of the UK population will be over 65 years old, bringing with it important health challenges. A thorough understanding of the mechanisms that contribute to the development of immunosenescence is therefore crucial to help identify novel approaches to improve mucosal immunity in the elderly. PMID:24705962

  3. Small intestinal mucosal abnormalities in post-perinatal deaths.

    PubMed

    Variend, S; Sunderland, R

    1984-03-01

    Examination of small intestinal mucosa from cases of post-perinatal death in Sheffield between September 1980 and September 1981 showed mucosal changes before death in 18 of 78 cases (20%). There was no significant difference in prevalence between explained and unexplained deaths, nor was there any positive association with viral isolation from the small intestine. The lesion was much more common in males than females and showed a strong association with bottle feeding--no infant wholly breast fed showed an enteropathy. There was a low incidence of symptoms referrable to the gastrointestinal tract among affected infants, and no appreciable evidence of failure to thrive, as reflected by the postmortem body weight, was present. Mucosal changes of the small intestine in cases of sudden infant death syndrome have previously been reported and attributed to heatstroke. Although the finding of similar lesions in infants who died explicably does not appear to support this view, overheating is difficult to exclude as most of the explained deaths with a mucosal lesion occurred at home. PMID:6699191

  4. Enhancing the buccal mucosal delivery of peptide and protein therapeutics.

    PubMed

    Caon, Thiago; Jin, Liang; Simões, Cláudia M O; Norton, Raymond S; Nicolazzo, Joseph A

    2015-01-01

    With continuing advances in biotechnology and genetic engineering, there has been a dramatic increase in the availability of new biomacromolecules, such as peptides and proteins that have the potential to ameliorate the symptoms of many poorly-treated diseases. Although most of these macromolecular therapeutics exhibit high potency, their large molecular mass, susceptibility to enzymatic degradation, immunogenicity and tendency to undergo aggregation, adsorption, and denaturation have limited their ability to be administered via the traditional oral route. As a result, alternative noninvasive routes have been investigated for the systemic delivery of these macromolecules, one of which is the buccal mucosa. The buccal mucosa offers a number of advantages over the oral route, making it attractive for the delivery of peptides and proteins. However, the buccal mucosa still exhibits some permeability-limiting properties, and therefore various methods have been explored to enhance the delivery of macromolecules via this route, including the use of chemical penetration enhancers, physical methods, particulate systems and mucoadhesive formulations. The incorporation of anti-aggregating agents in buccal formulations also appears to show promise in other mucosal delivery systems, but has not yet been considered for buccal mucosal drug delivery. This review provides an update on recent approaches that have shown promise in enhancing the buccal mucosal transport of macromolecules, with a major focus on proteins and peptides. PMID:25168518

  5. Volatile Sulfur Compounds as a Predictor for Esophagogastroduodenal Mucosal Injury

    PubMed Central

    Yoo, Seung Hee; Jung, Hyeon Sik; Sohn, Wee Sik; Kim, Bong Hwan; Ku, Bon Ho; Kim, Young Saeng; Park, Sang Woon

    2008-01-01

    Background/Aims Halitosis is a symptom that bothers patients more socially than medically and its pathogenic mechanisms are unclear and treatment armamenterium is limited. Clinicians generally ignored active interventions. Since halitosis is closely associated with volatile sulfur compounds (VSCs), we used a Halimeter and gas chromatography to measure VSCs in patients with Helicobacter-pylori (H. pylori)-associated gastric diseases. Methods We categorized 72 patients with H. pylori infection into two groups based on their endoscopic findings: a non-erosive mucosal group (NE, n=24) and an erosive mucosal group (E, n=48). Halitosis was objectively assessed by applying either a Halimeter to breath air or gas chromatography to gastric juice. Simultaneously, the expression of VSC-generating enzyme was measured with reverse-transcriptase PCR using mRNA isolated from biopsy tissues. Results The levels of VSCs in exhaled breaths or aspirated gastric juices differed significantly between the NE and E groups (p<0.00001), suggesting that VSCs might reflect eroded epithelial damage induced by H. pylori infection. The expressions of cystathionine ?-synthase (CBS) and cystathionine ?-lyase (CSE) were broadly consistent with the degree of mucosal injury. Conclusions Erosive changes in esophagogastroduodenal mucosa were strongly correlated with increased VSC levels, suggesting that halitosis might result from H. pylori-associated erosive lesions. PMID:20485620

  6. Strategies for preventing mucosal cell-associated HIV transmission.

    PubMed

    Whaley, Kevin J; Mayer, Kenneth H

    2014-12-15

    Human immunodeficiency virus (HIV) may be transmitted through either cell-free virions or leukocytes harboring intracellular HIV in bodily fluids. In recent years, the early initiation of combination antiretroviral therapy leading to virological suppression has resulted in decreased HIV transmission to uninfected partners. Additionally, the efficacy of primary chemoprophylaxis with oral or topical antiretroviral regimens containing tenofovir (with or without emtricitabine) has been demonstrated. However, the efficacy of these approaches may be compromised by suboptimal adherence, decreased drug concentrations in mucosal compartments in women, and genital inflammation. Furthermore, in vitro studies on the effects of tenofovir on cell-associated HIV transmission have produced conflicting results. Preclinical studies suggest that combination preventive approaches may be most effective in stopping the transmission of HIV after mucosal exposure. Since the development of antibodies were found to correlate with protection in the only effective HIV vaccine trial, the administration of preformed mucosal and systemic antibodies may inform the development of safe and effective antibody-based oral, topical, and/or systemic preexposure prophylaxis agents and provide guidance in the development of HIV vaccines that effectively block cell-associated HIV transmission. PMID:25414423

  7. 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). Mucositis induced an increase in intestinal permeability and intestinal inflammation (p?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

  8. Cancer Treatment-Induced Mucositis Pain: Strategies for Assessment and Management

    PubMed Central

    Harris, Debra J

    2006-01-01

    Mucositis pain is a major clinical problem associated with cancer treatment. Mucosal tissue injury is a dose-limiting side effect and also limits nutritional intake and oral function, resulting in weight loss and nutritional deficits for many patients. The pathophysiology of mucositis is thought to be a complex array of cytokine-mediated events, which begins with mucosal atrophy and eventually leads to the painful ulceration of the mucosa. This article reviews current research related to pain management for mucositis. Effective treatment for mucositis pain must be targeted at the various factors involved in the pain experience. Although a number of interventions aimed to prevent and treat mucositis have been studied, there is little evidence to recommend any one treatment modality. While current strategies for pain management rely on general treatment for acute pain, research developments are aimed at targeting the specific receptors and enzymes involved in mucositis. As these breakthroughs become available clinically, thorough assessment and timely directed interventions must be implemented in order to limit patient distress from mucositis. This article presents an assessment tool specific to mucositis pain, including physical, functional, and pain parameters. PMID:18360600

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

    PubMed

    Gao, Weihua; Mizukawa, Yumiko; Nakatsu, Noriyuki; Minowa, Yosuke; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

    2010-09-15

    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 and 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 24h after dosing, and the other contained 14 probe sets that could detect glutathione depletors by any mechanism. These two sets, with appropriate scoring systems, could be promising biomarkers for preclinical examination of hepatotoxicity. PMID:20621112

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

    SciTech Connect

    Gao Weihua [Toxicogenomics Informatics Project, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 (Japan); Mizukawa, Yumiko [Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto 610-0395 (Japan); Nakatsu, Noriyuki; Minowa, Yosuke; Yamada, Hiroshi [Toxicogenomics Informatics Project, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 (Japan); Ohno, Yasuo [National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-Ku, Tokyo, 158-8501 (Japan); Urushidani, Tetsuro, E-mail: turushid@dwc.doshisha.ac.j [Toxicogenomics Informatics Project, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 (Japan); Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto 610-0395 (Japan)

    2010-09-15

    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 and 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 scoring systems, could be promising biomarkers for preclinical examination of hepatotoxicity.

  11. Effect of a carbohydrase mixture on ileal amino acid digestibility in extruded full-fat soybeans fed to finishing pigs.

    PubMed

    Ayoade, D I; Kiarie, E; Woyengo, T A; Slominski, B A; Nyachoti, C M

    2012-11-01

    Extrusion technology has been used successfully to improve the nutritive value of full-fat oilseeds via shear force and heat applied during passage through the extruder, exposing more peptide bonds to enzymatic hydrolysis. However, the fibrous portion of the seeds is largely intact after extrusion. Therefore, application of carbohydrase mixtures targeting nonstarch polysaccharides might further improve the nutritive value of extruded full-fat oilseeds. This hypothesis was investigated in a study involving 6 ileal-cannulated barrows (average initial BW = 75.0 kg) fed extruded full-fat, soybean- (FFSB) based diets, without or with a carbohydrase mixture (CM) to determine apparent ileal digestibility (AID) of energy and standardized ileal digestibility (SID) of AA. The CM supplement provided 500, 50, 400, 1200, 450, and 45 units of pectinase, cellulase, mannanase, xylanase, glucanase, and galactanase, respectively, per kilogram of diet. A basal diet was formulated to contain FFSB as the sole source of AA, whereas the CM diet was formulated by supplementing the basal diet with CM. Diets contained titanium dioxide as an indigestible marker. Diets were fed in a 2-period crossover design to give 6 observations per diet. Each experimental period lasted 7 d, including a 5-d adaptation period and 2-d ileal digesta collection period. The SID of N and AA were calculated using published values for ileal endogenous N and AA losses from our laboratory. Enzyme supplementation increased (P < 0.01) AID values of DM (68.7 vs. 65.7%), GE (74.6 vs. 70.5%), and N (64.2 vs. 58.5%). Greater (P < 0.05) AID values were recorded for Leu, Met + Cys, Thr, Cys, Ser, and Tyr in the CM diet compared with the basal diet. Compared with the basal diet, the CM diet had greater SID values for N (73.7 vs. 68.6%; P < 0.01), Met + Cys (59.9 vs. 52.2%; P < 0.05), and Thr (66.3 vs. 61.2%; P < 0.05). The average SID for indispensable and total AA increased by 3.4% and 3.8% units, respectively, after enzyme supplementation. In conclusion, enzyme supplementation increased the nutritive value of extruded FFSB for finishing pigs. PMID:22665649

  12. Fermentable non-starch polysaccharides increases the abundance of Bacteroides-Prevotella-Porphyromonas in ileal microbial community of growing pigs.

    PubMed

    Ivarsson, E; Roos, S; Liu, H Y; Lindberg, J E

    2014-11-01

    Most plant-origin fiber sources used in pig production contains a mixture of soluble and insoluble non-starch polysaccharides (NSP). The knowledge about effects of these sources of NSP on the gut microbiota and its fermentation products is still scarce. The aim of this study was to investigate effects of feeding diets with native sources of NSP on the ileal and fecal microbial composition and the dietary impact on the concentration of short-chain fatty acids (SCFA) and lactic acid. The experiment comprised four diets and four periods in a change-over design with seven post valve t-cecum cannulated growing pigs. The four diets were balanced to be similar in NSP content and included one of four fiber sources, two diets were rich in pectins, through inclusion of chicory forage (CFO) and sugar beet pulp, and two were rich in arabinoxylan, through inclusion of wheat bran (WB) and grass meal. The gut microbial composition was assessed with terminal restriction fragment (TRF) length polymorphism and the abundance of Lactobacillus spp., Enterobacteriaceae, Bacteroides-Prevotella-Porphyromonas and the ?-xylosidase gene, xynB, were assessed with quantitative PCR. The gut microbiota did not cluster based on NSP structure (arabinoxylan or pectin) rather, the effect was to a high degree ingredient specific. In pigs fed diet CFO, three TRFs related to Prevotellaceae together consisted of more than 25% of the fecal microbiota, which is about 3 to 23 times higher (P<0.05) than in pigs fed the other diets. Whereas pigs fed diet WB had about 2 to 22 times higher abundance (P<0.05) of Megasphaera elsdenii in feces and about six times higher abundance (P<0.05) of Lactobacillus reuteri in ileal digesta than pigs fed the other diets. The total amount of digested NSP (r=0.57; P=0.002), xylose (r=0.53; P=0.004) and dietary fiber (r=0.60; P=0.001) in ileal digesta were positively correlated with an increased abundance of Bacteroides-Prevotella-Porphyromonas. The effect on SCFA was correlated to specific neutral sugars where xylose increased the ileal butyric acid proportion, whereas arabinose increased the fecal butyric acid proportion. Moreover, chicory pectin increased the acetic acid proportion in both ileal digesta and feces. PMID:25046106

  13. The prone 12 o'clock position reduces ileal intubation time during colonoscopy compared to the left lateral 6 o'clock (standard) position

    PubMed Central

    2011-01-01

    Background Ileal intubation is the gold standard for a complete colonoscopy. However, despite evidence of clinical benefit ileoscopy is not always attempted due to perceived technical difficulty. Our aim was to compare time taken for ileal intubation using a new position-the prone 12 o'clock position (PP) with the standard method (left lateral 6 o'clock position-LLP). Methods We performed a pilot study using fluoroscopy to determine the best patient position for ileal intubation. This was the prone 12 o'clock position. Patients were colonoscoped in the left lateral position and then randomized to ileal intubation in the 6 o'clock position(LL) or the 12 o'clock (PP) position. Results 202 consecutive patients were referred for colonoscopy. Colonoscopy was performed on 150 patients [82 females, mean (SD) age 53 (16) years]. 75 patients were randomized for ileal intubation in the PP and 75 patients in the LLP. Overall, the ileum was successfully intubated in 145 (96%) patients [74 (98.7%) in the PP and71 (94.7%) in the LLP]. The median (Interquartile Range) ileal intubation time was 12 (10) seconds in the PP and 87 (82) seconds in the LLP (p < 0.0001; Mann-Whitney U test). The ileum was abnormal in 11 (7.5%) patients. Conclusions During colonoscopy, the prone 12 o'clock position gives a more direct approach to the ileo-caecal valve and significantly reduces ileal intubation time. Trial registration Trial registry: Sri Lanka Clinical Trial Registry Clinical trial registry number: SLCTR/2009/002 PMID:21816067

  14. Stimulation of ileal calcium absorption by sorbitol, L-xylose, or creatine via a decrease in luminal sodium concentration: relation with concomitant changes in enterocyte energy metabolism.

    PubMed

    Tardivel, S; Fournier, P; Dupuis, Y; Nabarra, B; Drueke, T; Lacour, B

    1994-04-01

    Ligated ileal loops, 30 cm in length, of 4-month-old male Wistar rats were instilled with 3 ml of a 10 mM CaCl2 solution (added with 0.25 muCi 45Ca) in the absence (control) or presence of 100mM sorbitol, L-xylose, or creatine. Ileal calcium (Ca) transport, measured by plasma 45Ca appearance, was found to be similar 30 minutes after fluid instillation in all four instances. However, thereafter, 45Ca appearance in plasma did not increase further in control animals whereas it increased twice as much during the subsequent 30 minutes in the presence of sorbitol, L-xylose, or creatine. However, when loops of similar length were instilled with only 1.0 ml of such solutions, the sorbitol effect was already observed during the first 30 minutes. The stimulation of ileal Ca absorption induced by the presence of sorbitol appeared to be due to a cellular effect, associated with a decreased flux across the paracellular pathway, as indicated by 3H-mannitol absorption. The presence of sorbitol in instilled ileal solution induced a significant decrease in luminal Na, K, bicarbonate, and Cl concentrations at each time point studied (30, 60, 120, or 240 minutes after instillation). Thirty minutes after instillation, no difference in soluble Ca concentration was observed between control and experimental rats. After 60 minutes, Ca concentration was dramatically decreased in control rats but it remained nearly constant in experimental animals. Thus, the presence of substances enhancing ileal Ca transport favored the maintenance of soluble Ca in ileal solution during longer time periods than their absence. In the ileal enterocyte, these substances induced a twofold increase of ATP content compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8062145

  15. Modulation of cadmium-induced oxidative stress in Ceratophyllum demersum by zinc involves ascorbate-glutathione cycle and glutathione metabolism.

    PubMed

    Aravind, Parameswaran; Prasad, Majeti Narasimha Vara

    2005-02-01

    To understand the interaction between Zn, an essential micronutrient and Cd, a non-essential element, Cd-10 microM and Zn supplemented (10, 50, 100, and 200 microM) Cd 10 microM treated Ceratophyllum demersum L. (Coontail), a free floating freshwater macrophyte was chosen for the study. Cadmium at 10 microM concentration decreased thiol content, enhanced oxidation of ascorbate (AsA) and glutathione (GSH) to dehydroascorbate (DHA) and glutathione disulfide (GSSG), respectively, a clear indication of oxidative stress. Zinc supplementation to Cd (10 microM) treated plants effectively restored thiols, inhibited oxidation of AsA and GSH maintaining the redox molecules in reduced form. Cd-10 microM slightly induced ascorbate peroxidase (APX, E.C. 1.11.1.11) but inhibited monodehydroascorbate reductase (MDHAR, E.C. 1.6.5.4), dehydroascorbate reductase (DHAR, E.C. 1.8.5.1) and glutathione reductase (GR, E.C. 1.6.4.2), enzymes of ascorbate-glutathione cycle (AGC). Zn supplementation restored and enhanced the functional activity of all the AGC enzymes (APX, MDHAR, DHAR and GR). Gamma-glutamylcysteine synthetase (gamma-GCS, E.C. 6.3.2.2) was not affected by Cd as well as Zn, but Zn supplements increased glutathione-S-transferase (GST, E.C. 2.5.1.18) activity to a greater extent than Cd and simultaneously restored glutathione peroxidase (GSH-PX, E.C. 1.11.1.9) activity impaired by Cd toxicity. Zn-alone treatments did not change above investigated parameters. These results clearly indicate the protective role of Zn in modulating the redox status of the plant system through the antioxidant pathway AGC and GSH metabolic enzymes for combating Cd induced oxidative stress. PMID:15820657

  16. Effects of pirenzepine on acute mucosal erosions, gastric acid and mucosal blood flow in the spinal rat stomach.

    PubMed

    Sigman, H H; Poleski, M H; Gillich, A

    1991-01-01

    The aim of this study was to examine the effects of varying doses of pirenzepine, a selective muscarinic subtype M1 antagonist, on the prevention of acute gastric mucosal lesions in male Sprague-Dawley rats subjected to spinal cord section at the C7 level. It was also intended to evaluate the effects of the drug on gastric acid output and gastric mucosal blood flow. Pirenzepine 1, 2.5 and 5 mg/kg every 2 h all caused a significant reduction in mean total ulcer length (p less than 0.01) compared to controls. This was associated with a significant decrease in acid output (p less than 0.05). There was no significant effect on gastric mucosa blood flow as measured by hydrogen gas clearance. These results indicate that the protective effects of pirenzepine on gastric mucosa, in the spinal rat model, are associated with the acid-inhibitory action of the drug and not on mucosal blood flow effects. PMID:1797596

  17. Feedback inhibition by thiols outranks glutathione depletion: a luciferase-based screen reveals glutathione-deficient ?-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 ?-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, are necessary to induce the transcription of sulfate assimilation genes during early cadmium stress. PMID:22283708

  18. Comparative evaluation of standardized ileal amino acid digestibility in protein supplements for piglets.

    PubMed

    Eklund, M; Sauer, N; Hörner, S; Rademacher, M; Mosenthin, R

    2012-12-01

    Standardized ileal digestibility (SID) of AA was determined in 6 protein ingredients for piglets. A basal diet based on corn (Zea mays) starch and casein was supplemented with fluid-bed-dried porcine intestinal mucosa hydrolysate, spray-dried porcine intestinal mucosa hydrolysate, soy (Glycine max) protein concentrate, 2 batches of soy protein, or full-fat soybeans. The SID of AA did not differ between the 4 soybean products (P > 0.05). Compared to most SID values in the 4 soybean products, SID of AA were lower in the 2 porcine intestinal mucosa hydrolysates (P ? 0.05). In conclusion, although the initial trypsin inhibitor contents in the raw soybeans have not been determined, high SID values in the 4 soybean products indicate that the different processing procedures used to manufacture these products were efficient to inactivate trypsin inhibitors. For most AA in the 2 porcine intestinal mucosa hydrolysates, drying procedure did not affect SID of AA, but SID values were generally lower compared to the 4 soybean products. PMID:23365314

  19. Laparoscopic Restorative Total Proctocolectomy With Ileal Pouch Anal Anastomosis for Familial Adenomatous Polyposis

    PubMed Central

    Palanivelu, C.; Sendhilkumar, K.; Parthasarathi, R.; Senthilnathan, P.; Maheshkumar, G.

    2008-01-01

    Background: Familial adenomatous polyposis is a hereditary disease characterized by the presence of thousands of colonic adenomas, which, if untreated, invariably undergo malignant transformation. Because this disease manifests at a young age, the laparoscopic approach to perform surgery would be desirable due to its cosmetic benefits. We describe our experience with this procedure and review the literature on the topic. Methods: This is a case series of 15 patients who underwent restorative proctocolectomy with ileo-anal pouch anastomosis for familial adenomatous polyposis between 2000 and 2007. The salient operative steps are described. Results: There were 9 males and 6 females, 32 to 52 years of age, with an average age of 44.8 years. The median body mass index was 21.5 (range, 17 to 28). Rectal cancer was already present in 4 patients at the time of diagnosis. The median operating time was 225 minutes. Mean blood loss was 60mL, with none of the patients requiring perioperative blood transfusion. None of the surgeries required conversion to the open approach. Bowel function resumed on the second postoperative day in 12 patients and on the third postoperative day in 3 patients. The median hospital stay was 8 days. Postoperatively, there was no mortality and no serious morbidity. Conclusion: Laparoscopic restorative proctocolectomy with ileal pouch anal anastomosis is a feasible surgery for familial adenomatous polyposis, and considering its cosmetic benefit, is a desirable option for this group of predominantly young patients. PMID:18765048

  20. Ileal pouch-anal anastomosis for chronic ulcerative colitis and familial polyposis coli complicated by adenocarcinoma.

    PubMed

    Taylor, B A; Wolff, B G; Dozois, R R; Kelly, K A; Pemberton, J H; Beart, R W

    1988-05-01

    Of 518 patients undergoing the ileal pouch-anal anastomosis (IPAA), 17 (13 with chronic ulcerative colitis [CUC] and four with familial polyposis coli [FPC] ) also had a total of 22 cancers of the colorectum. Tumors were concentrated distally (rectum 6; sigmoid colon 5; proximal colon 11) and were diagnosed preoperatively in eight patients. Histologic grade and stage were as follows: grade I, 36 percent; II, 23 percent; III, 23 percent; IV, 18 percent; stage A, 5 percent; B1, 32 percent; B2, 18 percent; C1 and C2, 45 percent. Median hospital stay was 17 days with no operative mortality. Relaparotomy was required in 35 percent (sepsis in four patients; obstruction in two) and minor procedures were done in 12 percent (anastomotic dilatation in one; rectovaginal fistula in one). Mean frequency of defecation was 6.4/day, 1.0/night; incidence of minor seepage, 17 percent (day), 50 percent night); incidence of pouchitis, 8 percent; intermittent dyspareunia, 17 percent of six women. One patient died from hepatic metastases nine months after operation. IPAA should be considered in favorable cancers complicating CUC or FPC, although it may be contraindicated in advanced rectal cancer, and may be unsuitable in advanced proximal cancer. PMID:2835217

  1. Ileal pouch-anal anastomosis. Reoperation for pouch-related complications.

    PubMed Central

    Galandiuk, S; Scott, N A; Dozois, R R; Kelly, K A; Ilstrup, D M; Beart, R W; Wolff, B G; Pemberton, J H; Nivatvongs, S; Devine, R M

    1990-01-01

    The aim was to assess the value of reoperative surgery for pouch-related complications after ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis and familial adenomatous polyposis. Between January 1981 and August 1989, 114 of 982 IPAA patients (12%) seen at the Mayo Clinic had complications directly related to IPAA that required reoperation. Among the 114 patients, the complications prevented initial ileostomy closure in 33 patients (25%), occurred after ileostomy closure in 68 patients (60%), and delayed ileostomy closure in the remaining patients. The salvage procedures performed included anal dilatation under anesthesia for anastomotic strictures, placement of setons and/or fistulotomy for perianal fistulae, unroofing of anastomotic sinuses, simple drainage and antibiotics for perianal abscesses, abdominal exploration with drainage of intra-abdominal abscesses with or without establishment of ileostomy, and complete or partial reconstruction of the reservoir for patients with inadequate emptying. None of the reoperated patients died. Reoperation led to restoration of pouch function in two thirds of patients and, of these, 70% had an excellent clinical outcome. However approximately 20% of the 114 pouches required excision. Excision was common, especially among patients who had pelvic sepsis. Salvage procedures for pouch-specific complications can be done safely and will restore pouch function in two thirds of patients. Complications after reoperation, however, may ultimately lead to loss of the reservoir in one in five patients. PMID:2171442

  2. Ileal digestibility of sunflower meal, pea, rapeseed cake, and lupine in pigs.

    PubMed

    Nørgaard, J V; Fernández, J A; Jørgensen, H

    2012-12-01

    The standardized ileal digestibility (SID) of CP and AA was evaluated in soybean (Glycine max) meal, sunflower (Helianthus annuus) meal, rapeseed cake, and field pea (Pisum sativum) using 10 pigs and in lupine (Lupinus angustifolius) using 7 pigs. Pigs were fitted with either a T-cannula or a steered ileocecal valve-cannula. Diets contained 170 to 186 g CP/kg DM. Endogenous losses of CP and AA were estimated by feeding a N-free diet. The SID was calculated using the average of Cr(2)O(3) and TiO(2) as indigestible markers and corrected for type of cannula. The SID of CP was greater (P < 0.05) for soybean meal and pea compared to sunflower meal, rapeseed cake, and lupine. The SID of Lys and His were lowest (P < 0.05) in sunflower meal, and the SID of Met and Val were lowest (P < 0.05) in lupine. These results imply soybean meal and pea to be a high-digestible protein source relative to sunflower meal, rapeseed cake, and especially lupine, although all tested feedstuffs seem appropriate for inclusion in diets for organic pigs. PMID:23365330

  3. Antimicrobial susceptibility of ileal symbiont intracellularis isolated from pigs with proliferative enteropathy.

    PubMed Central

    McOrist, S; Mackie, R A; Lawson, G H

    1995-01-01

    Proliferative enteropathy is caused by the microaerophilic obligate intracellular bacterium ileal symbiont (IS) intracellularis. Treatment of this disease is problematic because of the lack of in vivo or in vitro data on the activities of antimicrobial agents. A new procedure for determining the susceptibility of IS intracellularis was developed by using a tissue culture system which promotes the in vitro multiplication of this organism. Nineteen antimicrobial agents were evaluated in triplicate cultures for their intracellular and extracellular activities against up to three IS intracellularis strains isolated from pigs with proliferative enteropathy. The MIC was defined as the lowest concentration which prevented multiplication of 99% of the IS intracellularis isolates. Penicillin, erythromycin, difloxacin, virginiamycin, and chlortetracycline were the most active compounds tested, all with MICs of < or = 1 microgram/ml. Tiamulin and tilmicosin were the next most active compounds, with MICs of < or = 4 micrograms/ml. The MICs of aminoglycosides were generally > 32 micrograms/ml. Both lincomycin and tylosin were relatively inactive against the IS intracellularis strains tested, with MICs of 32 and 64 micrograms/ml, respectively. These results indicate that some compounds capable of intracytoplasmic accumulation and blocking bacterial protein synthesis were active against IS intracellularis strains isolated from pigs with proliferative enteropathy. The in vitro cultivation system shows promise as a method for studying the interaction between IS intracellularis and antimicrobial agents and for screening new antibiotics for use in therapy. PMID:7615747

  4. K? absorption by locust gut and inhibition of ileal K? and water transport by FGLamide allatostatins.

    PubMed

    Robertson, Lisa; Donini, Andrew; Lange, Angela B

    2014-09-15

    The scanning ion-selective electrode technique (SIET) was utilized for the first time in Locusta migratoria to characterize K(+) transport along the digestive tract and to determine the effect of two locust FGLamide allatostatins (FGLa/ASTs) on K(+) transport: a previously sequenced FGLa/AST from Schistocerca gregaria (Scg-AST-6; ARPYSFGL-NH2) and a newly sequenced FGLa/AST from L. migratoria (Locmi-FGLa/AST-2; LPVYNFGL-NH2). Regional differences in K(+) fluxes along the gut were evident, where K(+) efflux in vitro (or absorption into the hemolymph in vivo) was greatest at the anterior ileum, and lowest at the colon. Ileal K(+) efflux was inhibited by both Scg-AST-6 and Locmi-FGLa/AST-2, with maximal inhibition at 10(-10) and 10(-11) mol l(-1), respectively. Both FGLa/ASTs also inhibited cAMP-stimulated K(+) efflux from the ileum. Locmi-FGLa/AST-2 also inhibited efflux of water across the ileum. Locusts are terrestrial insects living in dry climates, risking desiccation and making water conservation a necessity. The results suggest that FGLa/ASTs may be acting as diuretics by increasing K(+) excretion and therefore increasing water excretion. Thus it is likely that FGLa/ASTs are involved in the control of hemolymph water and ion levels during feeding and digestion, to help the locust deal with the excess K(+) load (and subsequently fluid) when the meal is processed. PMID:25013112

  5. Midgut pain due to an intussuscepting terminal ileal lipoma: a case report

    PubMed Central

    2010-01-01

    Introduction The occurrence of intussusception in adults is rare. The condition is found in 1 in 1300 abdominal operations and 1 in 100 patients operated for intestinal obstruction. The child to adult ratio is 20:1. Case presentation A 52-year-old Irish Caucasian woman was investigated for a 3-month history of intermittent episodes of colicky midgut pain and associated constipation. Ileocolonoscopy revealed a pedunculated lesion in the terminal ileum prolapsing into the caecum. Computed tomography confirmed a smooth-walled, nonobstructing, low density intramural lesion in the terminal ileum with secondary intussusception. A laparoscopic small bowel resection was performed. Histology revealed a large pedunculated polypoidal mass measuring 4 × 2.5 × 2 cm consistent with a submucosal lipoma. She had complete resolution of her symptoms and remained well at 12-month follow-up. Conclusion This case highlights an unusual cause of incomplete small bowel obstruction successfully treated through interdisciplinary cooperation. Ileal lipomas are not typically amenable to endoscopic removal and require resection. This can be successfully achieved via a laparoscopic approach with early restoration of premorbid functioning. PMID:20181229

  6. A comparison of J and W pouches using an isolated ileal reservoir in pigs.

    PubMed

    Levitt, M D; Cohen, L D; Mahendrarajah, K; Gibbs, N

    1994-07-01

    A new model for studying ileal reservoirs was used to compare J and W pouches. Sixteen female piglets were operated on between 62 and 67 days of age (median = 65). An approximately 50 cm vascularized segment of terminal ileum was isolated from the faecal stream and intestinal continuity restored. The distal 40 cm of the isolated loop was opened along its antimesenteric border and the pouch constructed (J = 8, W = 8). The remaining proximal length of ileum was brought out through the abdominal wall as a mucous fistula. One piglet in the W pouch group died post-operatively and in another, spontaneous closure of the mucous fistula prevented access to the W pouch for testing leaving six W and eight J pouches for comparison. Compliance was tested at 4 weeks by measuring intrapouch pressure during continuous distension by water. The volumes instilled at pressures of 20, 40, 60 and 80 cm of water were compared using the Mann-Whitney U-Test. Volumes varied widely at all pressures within both study groups although W pouches tended to be of larger volume for any given pouch pressure (P = NS). The failure of this study to demonstrate more clearly a difference between J and W pouches may be due to the small numbers involved but the wide range of volumes seen raises doubts about the usefulness of this pouch model. PMID:8010920

  7. Temporal differential proteomes of Clostridium difficile in the pig ileal-ligated loop model.

    PubMed

    Janvilisri, Tavan; Scaria, Joy; Teng, Ching-Hao; McDonough, Sean P; Gleed, Robin D; Fubini, Susan L; Zhang, Sheng; Akey, Bruce; Chang, Yung-Fu

    2012-01-01

    The impact of Clostridium difficile infection (CDI) on healthcare is becoming increasingly recognized as it represents a major cause of nosocomial diarrhea. A rising number of CDI cases and outbreaks have been reported worldwide. Here, we developed the pig ileal-ligated loop model for semi-quantitative analysis comparing temporal differential proteomes in C. difficile following in vivo incubation with in vitro growth using isobaric tags for relative and absolute quantification (iTRAQ). Proteins retrieved from the in vitro cultures and the loop contents after 4, 8, and 12 h in vivo incubation were subjected to in-solution digestion, iTRAQ labeling, two-dimensional liquid chromatography/tandem mass spectrometry and statistical analyses. From a total of 1152 distinct proteins identified in this study, 705 proteins were available for quantitative measures at all time points in both biological and technical replicates; 109 proteins were found to be differentially expressed. With analysis of clusters of orthologous group and protein-protein network interactions, we identified the proteins that might play roles in adaptive responses to the host environment, hence enhancing pathogenicity during CDI. This report represents the quantitative proteomic analysis of C. difficile that demonstrates time-dependent protein expression changes under conditions that mimic in vivo infection and identifies potential candidates for diagnostic or therapeutic measures. PMID:23029131

  8. Familial jejuno-ileal diverticulitis: A case report and review of the literature

    PubMed Central

    Barton, Jeffrey S.; Karmur, Amit B.; Preston, Jennifer F.; Sheppard, Brett C.

    2014-01-01

    INTRODUCTION Jejuno-ileal diverticulitis (JID) is a rare entity, presenting with symptoms of failure to thrive, abdominal pain, obstruction, bleeding, and acute or chronic perforation with associated pneumoperitoneum. Currently no specific genetic abnormality has been identified that leads to JID. Treatment is based on control of symptoms associated with the disease. PRESENTATION OF CASE We describe a familial cohort of patients with JID, with associated symptoms of chronic pneumoperitoneum, including a proposed genetic inheritance pattern and pedigree. In addition, we will describe the operative treatment of one family member's JID and chronic pneumoperitoneum. DISCUSSION While JID is rare, this familial cohort demonstrates a pattern of inheritance most consistent with autosomal dominance. The pathology demonstrates true diverticula, unlike most previous descriptions of JID. The index patient was successfully treated by minimally invasive surgery. CONCLUSION Familial JID is a rare entity, without an identified genetic abnormality. Treatment of chronic symptoms currently focuses on non-operative management. While most case reports involve individual patients, this cohort may possess a genetic mutation with an autosomal dominant pattern of inheritance. Further study into patients with JID may reveal an underlying genetic abnormality associated with development of the disease. PMID:25460468

  9. Oral Mucositis Prevention and Management by Therapeutic Laser in Head and Neck Cancers

    PubMed Central

    Fekrazad, Reza

    2014-01-01

    Introduction: Oral mucositis is considered a severe complication in cancer patients receiving radiotherapy or chemotherapy for head and neck cancer. The aim of this review study was to assess the effect of low level laser therapy for prevention and management of oral mucositis in cancer patients. Methods: The electronic databases searched included Pubmed, ISI Web of Knowledge and Google scholar with keywords as “oral mucositis”, “low level laser therapy” from 2000 to 2013. Results: The results of most studies showed that photobiomodulation (PBM) reduced the severity of mucositis. Also, it can delay the appearance of severe mucositis. Conclusion: Low level laser therapy is a safe approach for management and prevention of oral mucositis. PMID:25606332

  10. Synthesis and properties of glutathione reductase in stressed peas

    Microsoft Academic Search

    E. Anne Edwards; Corine Enard; Gary P. Creissen; Philip M. Mullineaux

    1993-01-01

    We have subjected peas (Pisum sativum L.) to four different oxidative stresses: cold conditions (4 °C) in conjunction with light, treatment with paraquat, fumigation with ozone, and illumination of etiolated seedlings (greening). In crude extracts of leaves from stressed plants, an increase (up to twofold) in activity of glutathione reductase (GR) was observed which was consistent with previous reports from

  11. Glutathione S-transferase polymorphisms: influence on susceptibility to cancer

    Microsoft Academic Search

    Richard C Strange; John T Lear; Anthony A Fryer

    1998-01-01

    The glutathione S-transferase supergene family includes several loci that demonstrate well characterised polymorphisms. The apparently critical role of these enzymes in cellular protection from the cytotoxic and mutagenic effects of electrophiles suggest that alleles associated with impaired detoxification will confer an increased susceptibility to a wide range of diseases. This hypothesis has been examined in case control studies and while

  12. Reduced glutathione export during programmed cell death of Neurospora crassa.

    PubMed

    Fernandes, Andreia S; Castro, Ana; Videira, Arnaldo

    2013-08-01

    In a previous study, we demonstrated that staurosporine (STS) induces programmed cell death (PCD) in the fungus Neurospora crassa and that glutathione has the capability of inhibiting both STS-induced reactive oxygen species (ROS) formation and cell death. Here, we further investigated the role of glutathione in STS-induced PCD in N. crassa and observed an efflux of reduced glutathione (GSH) together with a change in the cell internal redox state to a more oxidative environment. This event was also observed with another PCD inducer, phytosphingosine (PHS), although externally added GSH did not prevent PHS-induced PCD. The nature of ROS, detected under the experimental conditions at which GSH export occurred, is also different in the two systems, predominantly superoxide in the case of STS and hydrogen peroxide in the case of PHS. In both cases, GSH export preceded the alterations in the plasma membrane that lead to selective dye permeation. We conclude that glutathione export in the context of PCD is not exclusive of certain mammalian cells and can be extended to Fungi, being an early PCD event in N. crassa. In addition, STS and PHS induce different PCD pathways in this fungus and the role of GSH export in each of them is likely different. PMID:23666236

  13. Functional Divergence in the Glutathione Transferase Superfamily in Plants

    E-print Network

    Davis, Ben G.

    Functional Divergence in the Glutathione Transferase Superfamily in Plants IDENTIFICATION OF TWO in Arabidopsis thaliana which differed from all other plant GSTs by containing a cysteine in place of a serine sites (1). In plants, all the GSTs described to date are dimers composed of 25-kDa subunits

  14. Cystamine induces AIF-mediated apoptosis through glutathione depletion.

    PubMed

    Cho, Sung-Yup; Lee, Jin-Haeng; Ju, Mi-Kyeong; Jeong, Eui Man; Kim, Hyo-Jun; Lim, Jisun; Lee, Seungun; Cho, Nam-Hyuk; Park, Hyun Ho; Choi, Kihang; Jeon, Ju-Hong; Kim, In-Gyu

    2015-03-01

    Cystamine and its reduced form cysteamine showed protective effects in various models of neurodegenerative disease, including Huntington's disease and Parkinson's disease. Other lines of evidence demonstrated the cytotoxic effect of cysteamine on duodenal mucosa leading to ulcer development. However, the mechanism for cystamine cytotoxicity remains poorly understood. Here, we report a new pathway in which cystamine induces apoptosis by targeting apoptosis-inducing factor (AIF). By screening of various cell lines, we observed that cystamine and cysteamine induce cell death in a cell type-specific manner. Comparison between cystamine-sensitive and cystamine-resistant cell lines revealed that cystamine cytotoxicity is not associated with unfolded protein response, reactive oxygen species generation and transglutaminase or caspase activity; rather, it is associated with the ability of cystamine to trigger AIF nuclear translocation. In cystamine-sensitive cells, cystamine suppresses the levels of intracellular glutathione by inhibiting ?-glutamylcysteine synthetase expression that triggers AIF translocation. Conversely, glutathione supplementation completely prevents cystamine-induced AIF translocation and apoptosis. In rats, cysteamine administration induces glutathione depletion and AIF translocation leading to apoptosis of duodenal epithelium. These results indicate that AIF translocation through glutathione depletion is the molecular mechanism of cystamine toxicity, and provide important implications for cystamine in the neurodegenerative disease therapeutics as well as in the regulation of AIF-mediated cell death. PMID:25549939

  15. GLUTATHIONE S-TRANSFERASE-MEDIATED METABOLISM OF BROMODICHLOROMETHANE

    EPA Science Inventory

    GLUTATHIONE s-TRANSFERASE-MEDIATED METABOLISM OF BROMODICHLOROMETHANE. M K Ross1 and R A Pegram2. 1Curriculum in Toxicology, University of North Carolina at Chapel Hill; 2Experimental Toxicology Division, NHEERL/ORD, United States Environmental Protection Agency, Research Triangl...

  16. Regulation of hepatic glutathione synthesis: current concepts and controversies

    Microsoft Academic Search

    SHELLY C. LU

    Glutathione (GSH) is an important intracellular peptide with multiple functions ranging from antioxidant defense to modulation of cell proliferation. GSH is synthesized in the cytosol of all mammalian cells in a tightly regulated manner. The major determinants of GSH synthesis are the avail- ability of cysteine, the sulfur amino acid precursor, and the activity of the rate-limiting enzyme, g-glu- tamylcysteine

  17. Balneotherapy and platelet glutathione metabolism in type II diabetic patients

    NASA Astrophysics Data System (ADS)

    Ohtsuka, Yoshinori; Yabunaka, Noriyuki; Watanabe, Ichiro; Noro, Hiroshi; Agishi, Yuko

    1996-09-01

    Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG; r=0.692, P<0.02). After 4 weeks of balneotherapy, the mean level of GSH showed no changes; however, in well-controlled patients (FPG <150 mg/dl), the level increased ( P<0.01) and in poorly controlled patients (FPG >150 mg/dl), the value decreased ( P<0.05). There was a negative correlation between glutathione peroxidase (GPX) activities and the levels of FPG ( r=-0.430, P<0.05). After balneotherapy, the activity increased in 5 patients, decreased in 3 patients and showed no changes (alteration within ±3%) in all the other patients. From these findings in diabetic patients we concluded: (1) platelet GSH synthesis appeared to be induced in response to oxidative stress; (2) lowered GPX activities indicated that the antioxidative defense system was impaired; and (3) platelet glutathione metabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.

  18. Plasma Glutathione Peroxidase Activity Is Reduced in Haemodialysis Patients

    Microsoft Academic Search

    Heather E. Roxborough; Caroline Mercer; Dorothy McMaster; A. Peter Maxwell; Ian S. Young

    1999-01-01

    Cardiovascular disease is the major cause of morbidity and mortality in patients with end-stage renal failure. Increased free radical production and antioxidant depletion may contribute to the greatly increased risk of atherosclerosis in these patients. Glutathione peroxidase (GPX) is an important antioxidant, the plasma form of which is synthesized mainly in the kidney (eGPX). The aim of this study was

  19. Molecular basis of glutathione reductase deficiency in human blood cells

    Microsoft Academic Search

    Nanne M. Kamerbeek; Rob van Zwieten; Martin de Boer; Gert Morren; Herma Vuil; Natalja Bannink; Carsten Lincke; Koert M. Dolman; Katja Becker; R. Heiner Schirmer; Stephan Gromer; Dirk Roos

    Hereditary glutathione reductase (GR) de- ficiency was found in only 2 cases when testing more than 15 000 blood samples. We have investigated the blood cells of 2 patients (1a and 1b) in a previously described family suffering from favism and cataract and of a novel patient (2) presenting with severe neonatal jaun- dice. Red blood cells and leukocytes of

  20. Blood Glutathione Disulfide: In Vivo Factor or in Vitro Artifact?

    Microsoft Academic Search

    Ranieri Rossi; Aldo Milzani; Isabella Dalle-Donne; Daniela Giustarini; Lorenzo Lusini; Roberto Colombo; Paolo Di Simplicio

    2002-01-01

    Background: The reported mean concentration of glu- tathione disulfide (GSSG) in human blood\\/erythrocytes varies widely (1 to >500 mol\\/L), as does that of reduced glutathione (GSH) to a lesser extent. We have identified and investigated possible pitfalls in measurement of both GSH and GSSG. Methods: We measured GSH and GSSG using a spec- trophotometer with a modification of the GSH

  1. Possible role of oxygen free radicals in ethanol-induced gastric mucosal damage in rats

    Microsoft Academic Search

    Istvan Szelenyi; Kay Brune

    1988-01-01

    The involvement of oxygen free radicals in the development of the ethanol-induced gastric mucosal damage has been investigated. We found that oral administration of superoxide dismutase reduced the incidence of ethanol-induced mucosal lesions. Reduction of superoxide dismutase activity by diethyldithiocarbamate led to a pronounced aggravation of mucosal damage. Inhibition of the chloride-bicarbonate channel by a stilbene derivative also aggravated the

  2. Nonmucosal Alphavirus Vaccination Stimulates a Mucosal Inductive Environment in the Peripheral Draining Lymph Node1

    PubMed Central

    Thompson, Joseph M.; Nicholson, Michael G.; Whitmore, Alan C.; Zamora, Melodie; West, Ande; Iwasaki, Akiko; Staats, Herman F.; Johnston, Robert E.

    2009-01-01

    The strongest mucosal immune responses are induced following mucosal Ag delivery and processing in the mucosal lymphoid tissues, and much is known regarding the immunological parameters which regulate immune induction via this pathway. Recently, experimental systems have been identified in which mucosal immune responses are induced following nonmucosal Ag delivery. One such system, footpad delivery of Venezuelan equine encephalitis virus replicon particles (VRP), led to the local production of IgA Abs directed against both expressed and codelivered Ags at multiple mucosal surfaces in mice. In contrast to the mucosal delivery pathway, little is known regarding the lymphoid structures and immunological components that are responsible for mucosal immune induction following nonmucosal delivery. In this study, we have used footpad delivery of VRP to probe the constituents of this alternative pathway for mucosal immune induction. Following nonmucosal VRP delivery, J chain-containing, polymeric IgA Abs were detected in the peripheral draining lymph node (DLN), at a time before IgA detection at mucosal surfaces. Further analysis of the VRP DLN revealed up-regulated ?4?7 integrin expression on DLN B cells, expression of mucosal addressin cell adhesion molecule 1 on the DLN high endothelia venules, and production of IL-6 and CC chemokines, all characteristics of mucosal lymphoid tissues. Taken together, these results implicate the peripheral DLN as an integral component of an alternative pathway for mucosal immune induction. A further understanding of the critical immunological and viral components of this pathway may significantly improve both our knowledge of viral-induced immunity and the efficacy of viral-based vaccines. PMID:18566424

  3. Mucosal Healing in Inflammatory Bowel Disease—A True Paradigm of Success?

    PubMed Central

    Dave, Maneesh

    2012-01-01

    Mucosal healing is gaining more acceptance as a measure of disease activity in Crohn's disease and ulcerative colitis, and it is also gaining acceptance as an endpoint in clinical trials. Recent publications have correlated achievement of mucosal healing with good outcomes. Currently, there is no validated definition of what constitutes mucosal healing in inflammatory bowel disease. In clinical trials of ulcerative colitis, mucosal healing has been achieved with 5-aminosalicylates, corticosteroids, azathioprine, and infliximab. For Crohn's disease, mucosal healing has been achieved with corticosteroids, infliximab, and adalimumab, and mucosal healing has been maintained with infliximab. Achievement of long-term mucosal healing has been associated with a decreased risk of colectomy and colorectal cancer in ulcerative colitis patients, a decreased need for cortico-steroid treatment in Crohn's disease patients, and a trend toward a decreased need for hospitalization in Crohn's disease patients. Unfortunately, assessment of mucosal healing requires regular use of endoscopy, which is associated with increased costs, patient discomfort, and side effects. Biomarkers such as fecal calprotec-tin, fecal lactoferrin, serum C-reactive protein, and fecal S1 00A1 2 have been shown to correlate with disease activity in ulcerative colitis and Crohn's disease; in the future, these biomarkers might be used as surrogate markers for mucosal healing. Newer clinical trials are incorporating mucosal healing as an endpoint for evaluation of efficacy. However, before mucosal healing will be sufficient to guide therapy, clinicians need a standard definition of mucosal healing and a consistently used, prospectively validated scale with good interobserver agreement. PMID:22347830

  4. Mucosal exposure to antigen: Cause or cure of type 1 diabetes?

    Microsoft Academic Search

    Georgia Fousteri; Matthias von Herrath; Damien Bresson

    2007-01-01

    The human gut offers more than 200 m2 of mucosal surface, where direct interactions between the immune system and foreign antigens take place to eliminate pathogens\\u000a or induce immune tolerance toward food antigens or normal gut flora. Therefore, mucosally administered antigens can induce\\u000a tolerance under certain circumstances. In autoimmune diabetes, mucosal vaccination with autoantigens elicits some efficacy\\u000a in restoring tolerance

  5. Imaging and retention measurements of selenium 75 homocholic acid conjugated with taurine, and the carbon 14 glycochol breath test to document ileal dysfunction due to late radiation damage.

    PubMed

    Olmos, R V; den Hartog Jager, F; Hoefnagel, C; Taal, B

    1991-01-01

    In order to assess ileal dysfunction in patients with complaints after pelvic radiation therapy, retention measurements and scintigraphic imaging with selenium 75 homocholic acid conjugated with taurine (75Se-HCAT), combined with the carbon 14 glycochol breath test, were evaluated in 39 patients. In 22 patients without ileal resection the results of the 75Se-HCAT test and the breath test differentiated between a normal functioning ileum (both tests negative) and ileal dysfunction as a cause of complaints (one or both tests positive). Among the patients with ileal dysfunction, the combination of both tests permitted those with bacterial overgrowth (breath test positive, 75Se-HCAT negative) to be separated from patients with evidence of bile acid malabsorption (75Se-HCAT positive, breath test positive or negative). In 17 patients with small-bowel resection, the 75Se-HCAT test helped to estimate the severity of bile acid malabsorption with implications for therapy. In this group the breath test was false-negative in 7 cases with abnormal 75Se-HCAT. Additional systematically performed scintigraphic imaging improved the accuracy of the 75Se-HCAT test, revealing cases with prolonged colonic accumulation of the radiopharmaceutical, causing spurious retention values. In conclusion, assessment of ileal dysfunction by nuclear medicine techniques in post-irradiation conditions provides information about the aetiology and therefore the possibility of adjustment in the clinical management. PMID:2044571

  6. [Effect of tobacco smoking on glutathione concentration in the blood].

    PubMed

    Bizo?, Anna; Milnerowicz, Halina

    2012-01-01

    The aim of present study was to determine the influence of tobacco smoking and age on reduced glutathione concentration in the blood. The study was performed in the blood of 65 subjects. The data on smoking which had been obtained from a direct personal interview were verified by determination of serum cotinine concentrations. Biological material was divided into groups of non-smokers and smokers. Malonylodialdehyde concentration in the plasma was measured by reaction with thiobarbituric acid. Concentration of cadmium was measured using graphite furnace atomic absorption spectrometry with Zeeman background correction. Reduced glutathione in the blood was measured using a previously developed method [11]. A significant increase of malonylodialdehyde concentration was observed in the blood of smokers > or = 20 cigarettes per day compared to nonsmoking person. Malonylodialdehyde level in the plasma of smokers <20 cigarettes per day did not differ with non-smokers. The highest cadmium concentration was observed in the whole blood of smokers > or = 20 cigarettes per day and it was about 4-fold higher compared to non-smoking people. Also smokers <20 cigarettes per day have higher cadmium concentration in the blood in comparison to non-smokers. Analyzing the impact of smoking intensity on reduced glutathione concentration it was a statistically significant increase in the blood of smokers > or = 20 cigarettes per day compared to nonsmoking person. Non-smoking and smokers <20 cigarettes per day had comparable levels of this antioxidant in the blood. A significant elevation in reduced glutathione concentration was observed in the blood of smokers < 30 years of age in comparison to nonsmoking persons < 30 and > 30 years of age. Our study confirmed that the reduced glutathione concentration in the body affects tobacco smoking and aging. PMID:23421037

  7. Short communication direct effect of Cd on glutathione S-transferase and glutathione reductase from Calystegia sepium.

    PubMed

    Lyubenova, Lyudmila; Götz, Christine; Golan-Goldhirsh, Avi; Schröder, Peter

    2007-01-01

    Interactions between heavy metals, glutathione, glutathione S-transferase (GST), and glutathione reductase (GR) are being investigated by many working groups, but evaluation of the direct effect of Cd+ on these enzymes in vitro is lacking. We report here the effect of cadmium (10, 50, 100, 250 microM CdSO4) on partially purified enzymes from Calystegia sepium. Plants were grown under normal field conditions without metals and the enzymes were extracted by Tris buffer and partially purified by ammonium sulphate fractionation and gel filtration. Glutathione S-transferase activity was measured with different substrates, i.e., 1-chloro-2,4-dinitrobenzene (CDNB), p-nitrobenzylchloride (NBC), and the herbicide Fluorodifen. GST activity was significantly lower in leaf compared to stem, flower, and rhizome and the inhibitory effect of Cd was obtained with NBC and Fluorodifen substrates at 250 microM. There was no effect of Cd on GR activity up to 250 microM. PMID:18246773

  8. CHARACTERIZATION OF DANSYLATED CYSTEINE, CYSTINE, GLUTATHIONE, AND GLUTATHIONE DISULFIDE BY NARROW BORE LIQUID CHROMATOGRAPHY - ELECTROSPRAY IONIZATION MASS SPECTROMETRY

    EPA Science Inventory

    A method using reversed phase high performance liquid chromtography/electrospray ionization-mass spectrometry (RP-LC/ESI-MS) has been developed to confirm the dientity of dansylated derivatives of cysteine (C) and glutathione (GSH), and their respective dimers, cystine (CSSC) and...

  9. Alterations of the mucosal immune system in inflammatory bowel disease.

    PubMed

    MacDermott, R P

    1996-12-01

    The normal intestinal immune system is under a balance in which proinflammatory and anti-inflammatory cells and molecules are carefully regulated to promote a normal host mucosal defense capability without destruction of intestinal tissue. Once this careful regulatory balance is disturbed, nonspecific stimulation and activation can lead to increased amounts of potent destructive immunologica and inflammatory molecules being produced and released. The concept of balance and regulation of normal mucosal immune and inflammatory events is indicative of how close the intestine is to developing severe inflammation. The normal intestinal mucosal immune system is constantly stimulated by lumenal contents and bacteria. The stimulatory molecules present in the intestinal lumen that activate and induce subsequent mucosal immunologic and inflammatory events include bacterial cell wall products, such as peptidoglycans and lipopolysaccharides, as well as other chemotactic and toxic bacterial products that are produced by the many different types of bacteria within the gastrointestinal tract. These highly stimulatory bacterial cell wall products are capable of activating macrophages and T lymphocytes to release potent proinflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). IL-1, IL-6, and TNF-alpha increase the presence of human leukocyte antigen (HLA) class II antigen-presenting molecules on the surfaces of epithelial cells, endothelial cells, macrophages, and B cells, thus increasing their ability to present lumenal antigens and bacterial products. The proinflammatory cytokines IL-1 and TNF-alpha also increase the ability of epithelial cells, endothelial cells, macrophages, and fibroblasts to secrete potent chemotactic cytokines, such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), which serve to increase the movement of macrophages and granulocytes from the circulation into the inflamed mucosa. Thus, through lumenal exposure to potent, nonspecific stimulatory bacterial products, the state of activation of the intestinal immune system and mucosal inflammatory pathways are markedly up-regulated. This raises the question of whether there is a deficiency in effective down-regulation through the absence of normally suppressive cytokines such as interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), interleukin-4 (IL-4), and IL-1 receptor antagonist. Normally, the turning off of the active and destructive immunologic and inflammatory events should occur following the resolution of a bacterial or viral infection that has been appropriately defended against and controlled by the mucosal immune system. In inflammatory bowel disease (IBD), however, the down-regulatory events and processes that should turn off the immunologic and inflammatory protective processes, once the pathogenic agent has been cleared, appear to be deficient or only partially effective. We may find that we ultimately are dealing with disease processes that have more than one genetic or cellular basis. The improved understanding of the immunopathophysiology of IBD will allow exploration of novel immunologic and genetic approaches, such as gene replacement therapy, administration of a suppressor cytokine or an altered cell surface antigen, the administration of humanized monoclonal antibodies directed against proinflammatory cytokines, or the development of newer strategies against fundamental cell biologic mechanisms such as adhesion molecules. PMID:9027661

  10. 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 met15? 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 ?m, 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 (dug3?) or transport (opt7?) of glutathione failed to show a defect in virulence. PMID:21994941

  11. Mucosal immunotherapy for protection from pneumonic infection with Francisella tularensis.

    PubMed

    Troyer, Ryan M; Propst, Katie L; Fairman, Jeff; Bosio, Catherine M; Dow, Steven W

    2009-07-16

    Previous studies have demonstrated that systemically administered immunotherapy can protect mice from systemic challenge with the bacterial pathogen Francisella tularensis. However, for protection from inhalational challenge with this bacterium, we wondered if mucosally administered immunotherapy might be more effective. Therefore, we administered cationic liposome-DNA complexes (CLDC), which are potent activators of innate immunity, intranasally (i.n.) and assessed the effectiveness of protection from lethal inhalational challenge with F. tularensis. We found that pretreatment by i.n. administration of CLDC 24h prior to bacterial challenge elicited nearly complete protection of BALB/c mice from lethal challenge with F. tularensis LVS strain. We also observed that mucosal CLDC immunotherapy provided a statistically significant increase in survival time in mice challenged with the highly virulent F. tularensis Schu4 strain. Protection was associated with a significant reduction in bacterial burden in the lungs, liver, and spleen. Mucosal administration of CLDC elicited significantly increased expression of IL-12, IFN-gamma, TNF-alpha, IFN-beta and IFN-alpha genes in the lung as detected by real-time quantitative PCR. In vitro treatment of F. tularensis infected macrophages with CLDC-elicited cytokines also significantly suppressed intracellular replication of F. tularensis in infected macrophages. In vivo, depletion of NK cells prior to administration of CLDC completely abolished the protective effects of CLDC immunotherapy. CLDC-elicited protection was also dependent on induction of IFN-gamma production in vivo. We conclude therefore that activation of local pulmonary innate immune responses is capable of eliciting significant protection from inhalational exposure to a virulent bacterial pathogen. PMID:19490961

  12. Mucosal microbiome in patients with recurrent aphthous stomatitis.

    PubMed

    Hijazi, K; Lowe, T; Meharg, C; Berry, S H; Foley, J; Hold, G L

    2015-03-01

    Recurrent aphthous stomatitis (RAS) is the most common disease affecting oral mucosae. Etiology is unknown, but several factors have been implicated, all of which influence the composition of microbiota residing on oral mucosae, which in turn modulates immunity and thereby affects disease progression. Although no individual pathogens have been conclusively shown to be causative agents of RAS, imbalanced composition of the oral microbiota may play a key role. In this study, we sought to determine composition profiles of bacterial microbiota in the oral mucosa associated with RAS. Using high-throughput 16S rRNA gene sequencing, we characterized the most abundant bacterial populations residing on healthy and ulcerated mucosae in patients with RAS (recruited using highly stringent criteria) and no associated medical conditions; we also compared these to the bacterial microbiota of healthy controls (HCs). Phylum-level diversity comparisons revealed decreased Firmicutes and increased Proteobacteria in ulcerated sites, as compared with healthy sites in RAS patients, and no differences between RAS patients with healthy sites and HCs. Genus-level analysis demonstrated higher abundance of total Bacteroidales in RAS patients with healthy sites over HCs. Porphyromonadaceae comprising species associated with periodontal disease and Veillonellaceae predominated in ulcerated sites over HCs, while no quantitative differences of these families were observed between healthy sites in RAS patients and HCs. Streptococcaceae comprising species associated with oral health predominated in HCs over ulcerated sites but not in HCs over healthy sites in RAS patients. This study demonstrates that mucosal microbiome changes in patients with idiopathic RAS-namely, increased Bacteroidales species in mucosae of RAS patients not affected by active ulceration. While these changes suggest a microbial role in initiation of RAS, this study does not provide data on causality. Within this limitation, the study contributes to the understanding of the potential role of mucosal microbiome changes in oral mucosal disease. PMID:25540188

  13. Intestinal dendritic cells in the regulation of mucosal immunity.

    PubMed

    Bekiaris, Vasileios; Persson, Emma K; Agace, William W

    2014-07-01

    The intestine presents a huge surface area to the outside environment, a property that is of critical importance for its key functions in nutrient digestion, absorption, and waste disposal. As such, the intestine is constantly exposed to dietary and microbial-derived foreign antigens, to which immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive immune responses. In the intestinal mucosa, DCs are located diffusely throughout the intestinal lamina propria, within gut-associated lymphoid tissues, including Peyer's patches and smaller lymphoid aggregates, as well as in intestinal-draining lymph nodes, including mesenteric lymph nodes. The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality of intestinal DCs. In the current review, we discuss recent findings from our group and others that have provided important insights regarding murine and human intestinal lamina propria DCs and highlighted marked developmental and functional heterogeneity within this compartment. A thorough understanding of the role these subsets play in the regulation of intestinal immune homeostasis and inflammation will help to define novel strategies for the treatment of intestinal pathologies and contribute to improved rational design of mucosal vaccines. PMID:24942684

  14. Impact of Mucosal Inflammation on Oral Simian Immunodeficiency Virus Transmission

    PubMed Central

    Chen, Hui-Ling; Hodara, Vida L.; Chu, Lianrui; Parodi, Laura M.; Smith, Lisa M.; Sexton, Valerie; Cappelli, David; Sodora, Donald L.

    2013-01-01

    Mucosal tissues are the primary route of transmission for most respiratory and sexually transmitted diseases, including human immunodeficiency virus (HIV). There is epidemiological evidence that genital mucosal inflammation leads to enhanced HIV type 1 (HIV-1) transmission. The objective of this study was to assess the influence of periodontal inflammation on oral HIV transmission using a nonhuman primate model of teeth ligature-induced periodontitis. Simian immunodeficiency virus (SIV) was nontraumatically applied to the gingiva after moderate gingivitis was identified through clinical and immunologic analyses (presence of inflammatory cytokines). Overall oral SIV infection rates were similar in the gingivitis-induced and control groups (5 infections following 12 SIV administrations for each), although more macaques were infected with multiple viral variants in the gingivitis group. SIV infection also affected the levels of antiviral and inflammatory cytokines in the gingival crevicular fluid, and a synergistic effect was observed, with alpha interferon and interferon-inducible protein 10 undergoing significant elevations following SIV infection in macaques with gingivitis compared to controls. These increases in antiviral and inflammatory immune modulators in the SIV-infected gingivitis macaques could also be observed in blood plasma, although the effects at both compartments were generally restricted to the acute phase of the infection. In conclusion, while moderate gingivitis was not associated with increased susceptibility to oral SIV infection, it resulted in elevated levels of cytokines in the oral mucosa and plasma of the SIV-infected macaques. These findings suggest a synergy between mucosal inflammation and SIV infection, creating an immune milieu that impacts the early stages of the SIV infection with potential implications for long-term pathogenesis. PMID:23175379

  15. The effect of dietary phosphorus and calcium level, phytase supplementation, and ileal infusion of pectin on the chemical composition and carbohydrase activity of fecal bacteria and the level of microbial metabolites in the gastrointestinal tract of pigs

    Microsoft Academic Search

    B. U. Metzler; R. Mosenthin; T. Baumgartel; M. Rodehutscord

    2008-01-01

    Two experiments with growing pigs were conducted to determine the effects of dietary P and Ca level, phytase supplementation, and ileal pectin infusion on ileal and fecal P and Ca balance, chemical composition of fecal mixed bacterial mass (MBM), and bacterial metabolic activity. Pigs (initial BW = 30 kg) were fitted with simple T-cannulas at the distal ileum. They were

  16. Effect of supplementation of xylanase and phospholipase to a wheat-based diet for weanling pigs on nutrient digestibility and concentrations of microbial metabolites in ileal digesta and feces1

    Microsoft Academic Search

    G. Diebold; R. Mosenthin; H.-P. Piepho; W. C. Sauer

    2010-01-01

    The objective of this study was to deter- mine the effect of supplementing a wheat-based diet with xylanase and phospholipase either alone or in com- bination on the ileal and fecal digestibilities of nutrients and energy in early-weaned pigs. In addition, the con- centrations of ammonia, lactate, and VFA were mea- sured in ileal digesta and feces. The experiment was

  17. Particulate Carrier Systems for Mucosal DNA Vaccine Delivery

    E-print Network

    Borchard, Gerrit

    2006-10-26

    % Hep C 2 M 42% HIV*96 k 2% *worldwide WHO/BHT/DCT/01.3, pp. 1-7 GPEN 2006 HIV infection changing paradigm: a ?tale of two infections? Picker & Watkins, Nat Immunol 6 (2005) 430 4 GPEN 2006 Mucosal surfaces are the port-of-entry for infectious diseases... of resistant strains ?MDR-TB rising, therapy is expensive GPEN 2006 M. tuberculosis, HIV have an intracellular lifestyle 11 GPEN 2006 Pathogen Genetic Material Gene for antigen plasmid altered plasmid Gene Gun Syringe Muscle Skin DNA Vaccines Introduction GPEN...

  18. Underwater endoscopic mucosal resection of large colorectal lesions.

    PubMed

    Uedo, Noriya; Nemeth, Artur; Johansson, Gabriele Wurm; Toth, Ervin; Thorlacius, Henrik

    2015-02-01

    In this prospective study, 11 consecutive patients with neoplastic colorectal lesions (median size 20?mm, range 15?-?25?mm) underwent endoscopic polyp removal by underwater endoscopic mucosal resection (EMR). Six lesions were removed en bloc and five lesions were removed by piecemeal resection. Pathological examination revealed seven R0 resections, and in four cases the pathology could not be determined. Two cases of procedure-related bleeding occurred but these were easily managed using hemostatic forceps and clip application. No perforations or delayed bleedings were observed. Underwater EMR is a relatively simple, safe, and useful method for the removal of large colorectal lesions. PMID:25314326

  19. Glutathione deficiency does not elevate susceptibility of bacteria to the mutagenicity of chlorinated humic acids.

    PubMed

    Ubom, G A; Chipman, J K; Hayes, M H

    1994-08-01

    1. Rat liver 9,000 g supernatant protected against the mutagenic effect of chlorinated hydrophilic macromolecular humic acids (CHMA) in Salmonella typhimurium strain TA100. 2. Protection against mutagenicity of CHMA was mediated by glutathione and was partially dependent on glutathione S-transferase activity. 3. In contrast to the above findings, CHMA showed lower mutagenicity in Salmonella typhimurium and Escherichia coli strains of bacteria that are deficient in glutathione compared to their mutagenicity in parental (glutathione-rich) bacterial strains. 4. Glutathione-deficient cells do not provide test systems with elevated sensitivity for the detection of mutagenic chlorinated humic substances. PMID:7946511

  20. S-methyl glutathione synthesis is catalyzed by the cheR methyltransferase in Escherichia coli.

    PubMed Central

    Terwilliger, T C; Bollag, G E; Sternberg, D W; Koshland, D E

    1986-01-01

    The cheR methyltransferase, known to be necessary for the methyl esterification of receptors involved in chemotaxis, is shown to be essential to the synthesis of S-methyl glutathione from glutathione and S-adenosylmethionine in intact Escherichia coli. S-Methyl glutathione is not, however, found to be essential for chemotaxis. It is suggested that the synthesis of S-methyl glutathione may be due to a "parasitic" reaction of glutathione with S-adenosylmethionine bound to the methyltransferase. PMID:3512532