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Sample records for ileal mucosal glutathione

  1. Probiotics Prevent Intestinal Barrier Dysfunction in Acute Pancreatitis in Rats via Induction of Ileal Mucosal Glutathione Biosynthesis

    PubMed Central

    Lutgendorff, Femke; Nijmeijer, Rian M.; Sandström, Per A.; Trulsson, Lena M.; Magnusson, Karl-Eric; Timmerman, Harro M.; van Minnen, L. Paul; Rijkers, Ger T.; Gooszen, Hein G.; Akkermans, Louis M. A.; Söderholm, Johan D.

    2009-01-01

    Background During acute pancreatitis (AP), oxidative stress contributes to intestinal barrier failure. We studied actions of multispecies probiotics on barrier dysfunction and oxidative stress in experimental AP. Methodology/Principal Findings Fifty-three male Spraque-Dawley rats were randomly allocated into five groups: 1) controls, non-operated, 2) sham-operated, 3) AP, 4) AP and probiotics and 5) AP and placebo. AP was induced by intraductal glycodeoxycholate infusion and intravenous cerulein (6 h). Daily probiotics or placebo were administered intragastrically, starting five days prior to AP. After cerulein infusion, ileal mucosa was collected for measurements of E. coli K12 and 51Cr-EDTA passage in Ussing chambers. Tight junction proteins were investigated by confocal immunofluorescence imaging. Ileal mucosal apoptosis, lipid peroxidation, and glutathione levels were determined and glutamate-cysteine-ligase activity and expression were quantified. AP-induced barrier dysfunction was characterized by epithelial cell apoptosis and alterations of tight junction proteins (i.e. disruption of occludin and claudin-1 and up-regulation of claudin-2) and correlated with lipid peroxidation (r>0.8). Probiotic pre-treatment diminished the AP-induced increase in E. coli passage (probiotics 57.4±33.5 vs. placebo 223.7±93.7 a.u.; P<0.001), 51Cr-EDTA flux (16.7±10.1 vs. 32.1±10.0 cm/s10−6; P<0.005), apoptosis, lipid peroxidation (0.42±0.13 vs. 1.62±0.53 pmol MDA/mg protein; P<0.001), and prevented tight junction protein disruption. AP-induced decline in glutathione was not only prevented (14.33±1.47 vs. 8.82±1.30 nmol/mg protein, P<0.001), but probiotics even increased mucosal glutathione compared with sham rats (14.33±1.47 vs. 10.70±1.74 nmol/mg protein, P<0.001). Glutamate-cysteine-ligase activity, which is rate-limiting in glutathione biosynthesis, was enhanced in probiotic pre-treated animals (probiotics 2.88±1.21 vs. placebo 1.94±0.55 nmol/min/mg protein; P<0.05) coinciding with an increase in mRNA expression of glutamate-cysteine-ligase catalytic (GCLc) and modifier (GCLm) subunits. Conclusions Probiotic pre-treatment diminished AP-induced intestinal barrier dysfunction and prevented oxidative stress via mechanisms mainly involving mucosal glutathione biosynthesis. PMID:19223985

  2. Alterations of the Ileal and Colonic Mucosal Microbiota in Canine Chronic Enteropathies

    PubMed Central

    Cassmann, Eric; White, Robin; Atherly, Todd; Wang, Chong; Sun, Yaxuan; Khoda, Samir; Mosher, Curtis; Ackermann, Mark; Jergens, Albert

    2016-01-01

    Background The intestinal microbiota is increasingly linked to the pathogenesis of chronic enteropathies (CE) in dogs. While imbalances in duodenal and fecal microbial communities have been associated with mucosal inflammation, relatively little is known about alterations in mucosal bacteria seen with CE involving the ileum and colon. Aim To investigate the composition and spatial organization of mucosal microbiota in dogs with CE and controls. Methods Tissue sections from endoscopic biopsies of the ileum and colon from 19 dogs with inflammatory bowel disease (IBD), 6 dogs with granulomatous colitis (GC), 12 dogs with intestinal neoplasia, and 15 controls were studied by fluorescence in situ hybridization (FISH) on a quantifiable basis. Results The ileal and colonic mucosa of healthy dogs and dogs with CE is predominantly colonized by bacteria localized to free and adherent mucus compartments. CE dogs harbored more (P < 0.05) mucosal bacteria belonging to the Clostridium-coccoides/Eubacterium rectale group, Bacteroides, Enterobacteriaceae, and Escherichia coli versus controls. Within the CE group, IBD dogs had increased (P < 0.05) Enterobacteriaceae and E. coli bacteria attached onto surface epithelia or invading within the intestinal mucosa. Bacterial invasion with E. coli was observed in the ileal and colonic mucosa of dogs with GC (P < 0.05). Dogs with intestinal neoplasia had increased (P < 0.05) adherent (total bacteria, Enterobacteriaceae, E. coli) and invasive (Enterobacteriaceae, E. coli, and Bacteroides) bacteria in biopsy specimens. Increased numbers of total bacteria adherent to the colonic mucosa were associated with clinical disease severity in IBD dogs (P < 0.05). Conclusion Pathogenic events in canine CE are associated with different populations of the ileal and colonic mucosal microbiota. PMID:26840462

  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. Artemisia supplementation differentially affects the mucosal and luminal ileal microbiota of diet-induced obese mice

    PubMed Central

    Shawna, Wicks; M., Taylor Christopher; Meng, Luo; Eugene, Blanchard IV; David, Ribnicky; T., Cefalu William; L., Mynatt Randall; A., Welsh David

    2014-01-01

    Objective The gut microbiome has been implicated in obesity and metabolic syndrome; however, most studies have focused on fecal or colonic samples. Several species of Artemisia have been reported to ameliorate insulin signaling both in vitro and in vivo. The aim of this study was to characterize the mucosal and luminal bacterial populations in the terminal ileum with or without supplementation with Artemisia extracts. Materials/Methods Following 4 weeks of supplementation with different Artemisia extracts (PMI 5011, Santa or Scopa), diet-induced obese mice were sacrificed and luminal and mucosal samples of terminal ileum were used to evaluate microbial community composition by pyrosequencing of 16S rDNA hypervariable regions. Results Significant differences in community structure and membership were observed between luminal and mucosal samples, irrespective of diet group. All Artemisia extracts increased the Bacteroidetes:Firmicutes ratio in mucosal samples. This effect was not observed in the luminal compartment. There was high inter-individual variability in the phylogenetic assessments of the ileal microbiota, limiting the statistical power of this pilot investigation. Conclusions Marked differences in bacterial communities exist dependent upon the biogeographic compartment in the terminal ileum. Future studies testing the effects of Artemisia or other botanical supplements require larger sample sizes for adequate statistical power. PMID:24985102

  5. Acrylonitrile-induced gastric mucosal necrosis: role of gastric glutathione.

    PubMed

    Ghanayem, B I; Boor, P J; Ahmed, A E

    1985-02-01

    Acrylonitrile [vinyl cyanide (VCN)] induces acute hemorrhagic focal superficial gastric mucosal necrosis or gastric erosions. In this report the authors have studied the mechanism of the VCN-induced gastric erosions. VCN-induced gastric lesions are coupled with a marked decrease of gastric reduced glutathione (GSH) concentration. Pretreatment of rats with various metabolic modulators (cytochrome P-450 monooxygenase and GSH) before VCN demonstrated that there is an inverse and highly significant correlation between gastric GSH concentration and the VCN-induced gastric erosions. Pretreatment of rats with sulfhydryl-containing compounds protected against the VCN-induced gastric necrosis and blocked the VCN-induced gastric GSH depletion. Furthermore, pretreatment of rats with atropine, which blocks muscarinic receptors, protected rats against the VCN-induced gastric erosions. The working hypothesis is that depletion and/or inactivation of critical endogenous sulfhydryl groups causes configurational changes of cholinergic receptors and increases agonist binding affinity, which, among other actions, leads to the causation of gastric mucosal erosions. PMID:3968646

  6. Optimal dietary true ileal digestible threonine for supporting the mucosal barrier in small intestine of weanling pigs.

    PubMed

    Wang, Weiwei; Zeng, Xiangfang; Mao, Xiangbing; Wu, Guoyao; Qiao, Shiyan

    2010-05-01

    Threonine is of great importance for the maintenance of intestinal health. However, little is known about the optimal level of dietary threonine for neonates or the underlying mechanisms of its beneficial action. Our objective in this study was to determine the effects of graded levels of true ileal digestible (TID) threonine on the intestinal mucosal barrier in weanling pigs. Four groups of piglets (n = 8/group) were fed for 14 d diets containing 0.37, 0.74, 0.89, or 1.11% TID threonine. The duodenal mucosa of piglets fed the 0.37 and 1.11% TID threonine diets exhibited distorted villus architecture. Compared with pigs fed the 0.74 and 0.89% TID threonine diets, apoptosis was higher (P < 0.05) in pigs fed the 1.11% TID threonine diet. Feeding 0.37 and 1.11% TID threonine reduced (P < 0.05) concentrations of ileal acidomucins and duodenal sulfomucins, respectively, compared with the 0.74% TID threonine group. Compared with piglets fed the 0.89% TID threonine diet, the total amounts of mucins in duodenum, as well as expression of MUC2 mRNA in duodenum and jejunum, were reduced (P < 0.05) in piglets fed the 0.37 and 1.11% TID threonine diets. Collectively, these findings indicate that a deficiency or excess of dietary threonine affects the intestinal mucosal barrier and that the optimal level of dietary TID threonine for supporting gut barrier function is 0.89% for weanling pigs. These new findings have important implications for both the maintenance of normal physiological functions and the prevention of gut-related diseases in neonates. PMID:20335627

  7. Intestinal glutathione: determinant of mucosal peroxide transport, metabolism, and oxidative susceptibility.

    PubMed

    Aw, Tak Yee

    2005-05-01

    The intestine is a primary site of nutrient absorption and a critical defense barrier against dietary-derived mutagens, carcinogens, and oxidants. Accumulation of oxidants like peroxidized lipids in the gut lumen can contribute to impairment of mucosal metabolic pathways, enterocyte dysfunction independent of cell injury, and development of gut pathologies, such as inflammation and cancer. Despite this recognition, we know little of the pathways of intestinal transport, metabolism, and luminal disposition of dietary peroxides in vivo or of the underlying mechanisms of lipid peroxide-induced genesis of intestinal disease processes. This chapter summarizes our current understanding of the determinants of intestinal absorption and metabolism of peroxidized lipids. I will review experimental evidence from our laboratory and others (Table 1) supporting the pivotal role that glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) play in mucosal transport and metabolism of lipid hydroperoxides and how reductant availability can be compromised under chronic stress such as hypoxia, and the influence of GSH on oxidative susceptibility, and redox contribution to genesis of gut disorders. The discussion is pertinent to understanding dietary lipid peroxides and GSH redox balance in intestinal physiology and pathophysiology and the significance of luminal GSH in preserving the integrity of the intestinal epithelium. PMID:15845421

  8. Intestinal glutathione: determinant of mucosal peroxide transport, metabolism, and oxidative susceptibility

    SciTech Connect

    Aw, Tak Yee . E-mail: taw@lsuhsc.edu

    2005-05-01

    The intestine is a primary site of nutrient absorption and a critical defense barrier against dietary-derived mutagens, carcinogens, and oxidants. Accumulation of oxidants like peroxidized lipids in the gut lumen can contribute to impairment of mucosal metabolic pathways, enterocyte dysfunction independent of cell injury, and development of gut pathologies, such as inflammation and cancer. Despite this recognition, we know little of the pathways of intestinal transport, metabolism, and luminal disposition of dietary peroxides in vivo or of the underlying mechanisms of lipid peroxide-induced genesis of intestinal disease processes. This chapter summarizes our current understanding of the determinants of intestinal absorption and metabolism of peroxidized lipids. I will review experimental evidence from our laboratory and others (Table 1) supporting the pivotal role that glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) play in mucosal transport and metabolism of lipid hydroperoxides and how reductant availability can be compromised under chronic stress such as hypoxia, and the influence of GSH on oxidative susceptibility, and redox contribution to genesis of gut disorders. The discussion is pertinent to understanding dietary lipid peroxides and GSH redox balance in intestinal physiology and pathophysiology and the significance of luminal GSH in preserving the integrity of the intestinal epithelium.

  9. 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

  10. Glutathione.

    PubMed

    Alanazi, Amer M; Mostafa, Gamal A E; Al-Badr, Abdullah A

    2015-01-01

    Glutathione is an endogenous peptide with antioxidant and other metabolic functions. The nomenclature, formulae, elemental composition, and appearance and uses of the drug are included. The methods used for the synthesis and biosynthesis of glutathione are described. This profile contains the physical characteristics of the drug including: solubility, X-ray powder diffraction pattern, crystal structure, melting point, and differential scanning calorimetry. The spectral methods that were used for both the identification and analysis of glutathione include ultraviolet spectrum, vibrational spectrum, 1H and 13C nuclear magnetic resonance spectra, and mass spectrum. The profile also includes the compendial methods of analysis and the other methods of analysis that are reported in the literature. These other methods of e-analysis are: potentiometric, voltammetric, amperometric, spectrophotometric, specrtofluorometric, chemiluminescence, chromatographic and immunoassay methods. The stability of and several reviews on drug are also provided. More than 170 references are listed at the end this comprehensive profile on glutathione. PMID:26051685

  11. Biliary glutathione promotes the mucosal metabolism of luminal peroxidized lipids by rat small intestine in vivo.

    PubMed Central

    Aw, T Y

    1994-01-01

    We previously found that exogenous GSH enhances mucosal GSH and promotes lipid hydroperoxide metabolism by rat small intestine (AW, T. Y., and M. W. WIlliams, 1992. Am. J. Physiol. 263:G665-G672). In this study, we have developed an in vivo bile and lymph fistula rat model to test the hypothesis that biliary GSH is an important luminal source of GSH. Peroxidized fish oil was infused into the proximal intestine, and hydroperoxide accumulation in lumen, mucosa, and lymph was determined. Diversion of bile decreased mucosal GSH and increased hydroperoxide accumulation in all fractions. Supplementation with GSH, but not with GSSG, increased tissue GSH and attenuated hydroperoxide accumulation (50-60%), consistent with enhancement of hydroperoxide removal by exogenous GSH. Addition of native bile deficient in GSH, but not cysteine, cystine, or GSSG, decreased luminal and lymph hydroperoxide levels by 20-30%. Amino acid supplementation concurrently attenuated hydroperoxide recoveries in these fractions by 30-40% and increased mucosal GSH by 40%, indicating a role for biliary amino acids in hydroperoxide elimination. The effect of amino acids was abolished by buthionine sulfoximine, confirming their role in GSH biosynthesis. Collectively, the results demonstrate that bile is a rich source of reductant for maintaining mucosal GSH to promote intestinal metabolism of luminal peroxidized lipids. Images PMID:8083363

  12. Systemic and mucosal immune responses after intranasal administration of recombinant Mycobacterium bovis bacillus Calmette-Gurin expressing glutathione S-transferase from Schistosoma haematobium.

    PubMed

    Kremer, L; Dupr, L; Riveau, G; Capron, A; Locht, C

    1998-12-01

    A major goal of current vaccine development is the induction of strong immune responses against protective antigens delivered by mucosal routes. One of the most promising approaches in that respect relies on the use of live recombinant vaccine carriers. In this study, Mycobacterium bovis BCG was engineered to produce an intracellular glutathione S-transferase from Schistosoma haematobium (Sh28GST). The gene encoding Sh28GST was placed under the control of the mycobacterial hsp60 promoter on a replicative shuttle plasmid containing a mercury resistance operon as the only selectable marker. The recombinant Sh28GST produced in BCG bound glutathione and expressed enzymatic activity, indicating that its active site was properly folded. Both intraperitoneal and intranasal immunizations of BALB/c mice with the recombinant BCG resulted in strong anti-Sh28GST antibody responses, which were enhanced by a boost. Mice immunized intranasally produced a mixed response with the production of Sh28GST-specific immunoglobulin G1 (IgG1), IgG2a, IgG2b, and IgA in the serum. In addition, high levels of anti-Sh28GST IgA were also found in the bronchoalveolar lavage fluids, demonstrating that intranasal delivery of the recombinant BCG was able to induce long-lasting secretory and systemic immune responses to antigens expressed intracellularly. Surprisingly, intranasal immunization with the BCG producing the Sh28GST induced a much stronger specific humoral response than intranasal immunization with BCG producing the glutathione S-transferase from Schistosoma mansoni, although the two antigens have over 90% identity. This difference was not observed after intraperitoneal administration. PMID:9826340

  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. Cystolitholapaxy in Ileal Conduit

    PubMed Central

    Cohen, Jesse; Giuliano, Katherine; Sopko, Nikolai; Gandhi, Nilay; Jayram, Gautam; Matlaga, Brian R.

    2015-01-01

    Urolithiasis is a common complication of surgically treated bladder exstrophy. We report the case of a 43-year-old woman with a history of exstrophy, cystectomy, and ileal conduit urinary diversion presenting with a large calculus at the stomal neck of her conduit in the absence of a structural defect. PMID:26793546

  15. Bile Acids Induce Ileal Damage During Experimental Necrotizing Enterocolitis

    PubMed Central

    Halpern, Melissa D.; Holubec, Hana; Saunders, Tara A.; Dvorak, Katerina; Clark, Jessica A.; Doelle, Sarah M.; Ballatori, Nazzareno; Dvorak, Bohuslav

    2011-01-01

    Background & Aims Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants. While the effect of bile acids (BAs) on intestinal mucosal injury is known, we investigated the contribution of BAs during the development of NEC in neonatal rats. Methods Premature rats were fed with cows milkbased formula and subjected to asphyxia and cold stress to develop NEC. Jejunal and ileal luminal BAs, portal blood BAs, and messenger RNA and protein for the apical sodium-dependent bile acid transporter, the ileal bile acid binding protein, and the heteromeric organic solute transporter (Ost?/Ost?)were evaluated. Results Ileal luminal BAs levels were increased significantly during disease development and the removal of ileal BAs significantly decreased the incidence and severity of disease. Furthermore, when NEC was reduced via treatment with epidermal growth factor (EGF), BA levels were reduced significantly. Jejunal luminal BA levels were similar between animals with NEC and controls, but portal/ileal luminal BA ratios were decreased significantly in animals with NEC. The apical sodium-dependent bile acid transporter was up-regulated at the site of injury in animals with NEC and decreased after EGF treatment; however, the ileal bile acid binding protein was up-regulated only in the NEC and EGF group. Ost?/Ost? expression was low in all groups, and only slightly increased in the NEC group. Conclusions These data strongly suggest that BAs play a role in the development of ileal damage in experimental NEC and that alterations in BA transport in the neonatal ileum may contribute to disease development. PMID:16472592

  16. Mucosal adjuvants.

    PubMed

    Harandi, Ali M; Medaglini, Donata

    2010-06-01

    The vast majority of pathogens invade the body through or establish infections in the mucosal tissues. Development of vaccines to combat mucosal infections represents a top priority. Mucosal immunization has recently attracted much interest as a means of generating protective immunity against mucosal pathogens. Conversely, only very few mucosal vaccines are presently approved for human use. The development of a broad range of mucosal vaccines will necessitate the development of safe and effective mucosal adjuvants and delivery systems. Over the past decade, a number of immunomodulatory agents, including toxin based adjuvants, Toll like receptor (TLR) mimetics and non TLR-targeting immunostimulators as well as delivery systems have shown promise for mucosal administration in experimental animals. However, their possible use in humans remains to be established. This paper attempts to provide a brief overview of the mucosal immunization and adjuvants with an emphasis on mucosal adjuvants in or close to clinic. PMID:20353395

  17. The schistosome glutathione S-transferase P28GST, a unique helminth protein, prevents intestinal inflammation in experimental colitis through a Th2-type response with mucosal eosinophils

    PubMed Central

    Driss, V; El Nady, M; Delbeke, M; Rousseaux, C; Dubuquoy, C; Sarazin, A; Gatault, S; Dendooven, A; Riveau, G; Colombel, J F; Desreumaux, P; Dubuquoy, L; Capron, M

    2016-01-01

    Intestinal helminth parasites are potent inducers of T helper type 2 (Th2) response and have a regulatory role, notably on intestinal inflammation. As infection with schistosomes is unlikely to provide a reliable treatment of inflammatory bowel diseases, we have investigated the beneficial effect of a schistosome enzymatic protein, the 28-kDa glutathione S-transferase (P28GST), on the modulation of disease activity and immune responses in experimental colitis. Our results showed that immunization with recombinant P28GST is at least as efficient as established schistosome infection to reduce colitis lesions and expression of pro-inflammatory cytokines. Considering underlying mechanisms, the decrease of inflammatory parameters was associated with the polarization of the immune system toward a Th2 profile, with local and systemic increases of interleukin (IL)-13 and IL-5. Dense eosinophil infiltration was observed in the colons of P28GST-immunized rats and mice. Depletion of eosinophils by treatment with an anti-Siglec-F monoclonal antibody and use of IL-5-deficient mice led to the loss of therapeutic effect, suggesting the crucial role for eosinophils in colitis prevention by P28GST. These findings reveal that immunization with P28GST, a unique recombinant schistosome enzyme, ameliorates intestinal inflammation through eosinophil-dependent modulation of harmful type 1 responses, representing a new immuno-regulatory strategy against inflammatory bowel diseases. PMID:26174763

  18. The schistosome glutathione S-transferase P28GST, a unique helminth protein, prevents intestinal inflammation in experimental colitis through a Th2-type response with mucosal eosinophils.

    PubMed

    Driss, V; El Nady, M; Delbeke, M; Rousseaux, C; Dubuquoy, C; Sarazin, A; Gatault, S; Dendooven, A; Riveau, G; Colombel, J F; Desreumaux, P; Dubuquoy, L; Capron, M

    2016-03-01

    Intestinal helminth parasites are potent inducers of T helper type 2 (Th2) response and have a regulatory role, notably on intestinal inflammation. As infection with schistosomes is unlikely to provide a reliable treatment of inflammatory bowel diseases, we have investigated the beneficial effect of a schistosome enzymatic protein, the 28-kDa glutathione S-transferase (P28GST), on the modulation of disease activity and immune responses in experimental colitis. Our results showed that immunization with recombinant P28GST is at least as efficient as established schistosome infection to reduce colitis lesions and expression of pro-inflammatory cytokines. Considering underlying mechanisms, the decrease of inflammatory parameters was associated with the polarization of the immune system toward a Th2 profile, with local and systemic increases of interleukin (IL)-13 and IL-5. Dense eosinophil infiltration was observed in the colons of P28GST-immunized rats and mice. Depletion of eosinophils by treatment with an anti-Siglec-F monoclonal antibody and use of IL-5-deficient mice led to the loss of therapeutic effect, suggesting the crucial role for eosinophils in colitis prevention by P28GST. These findings reveal that immunization with P28GST, a unique recombinant schistosome enzyme, ameliorates intestinal inflammation through eosinophil-dependent modulation of harmful type 1 responses, representing a new immuno-regulatory strategy against inflammatory bowel diseases. PMID:26174763

  19. Mucosal adjuvants.

    PubMed

    Stevceva, L; Ferrari, M G

    2005-01-01

    Vaccines delivered through mucosal surfaces are increasingly studied because of their properties to effectively induce mucosal immune responses, are cheap, easily administrable and suitable for mass vaccinations. The prospects of development of edible and intranasally administered (perhaps through nose drops or spray) vaccines are inciting a lot of interest and generating many studies. One major obstacle is to be able to induce systemic as well as mucosal responses to mucosal vaccines. Apart from immunizing with live viruses, this has proven to be a challenge and one way to overcome it is by using adjuvants. It is well established that toxins with little or no capacity to activate adenylate cyclase and thus lacking toxicity (CT or mutant Echerichia Coli labile toxin) improve performance of mucosal vaccines. Synthetic oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG) have synergistic action with other adjuvants, such as alum and CT when delivered mucosally. There are several other important candidates for use as mucosal adjuvants. The proinflammatory cytokines IL-1alpha, IL-12, and IL-18 can replace CT as a mucosal adjuvant for antibody induction and induce an increase of mucosal CTL's. IL-15 also has the potential to increase antigen-specific CTL activity when used as an adjuvant while IL-5 and IL-6 were shown to be able to markedly increase IgA reactivity to co-expressed heterologous antigen. Chemokines such as MCP-1 could also be used as potential adjuvant for mucosally administered DNA vaccines as it significantly increases mucosal IgA secretion and CTL responses. PMID:15777234

  20. Oral mucositis

    MedlinePLUS

    Radiation therapy or chemotherapy may cause mucositis (tissue swelling) in your mouth. You may have symptoms such as: ... sores. Infection. Bleeding, if you are getting chemotherapy. Radiation therapy usually does not lead to bleeding. With chemotherapy, ...

  1. Endorectal ileal pullthrough with isoperistaltic ileal reservoir for colitis and polyposis.

    PubMed Central

    Fonkalsrud, E W

    1985-01-01

    Seventy-eight patients with ulcerative colitis refractory to medical therapy and eight with colonic polypisis have undergone total colectomy mucosal proctectomy, endorectal ileal pull-through with ileoanal anastomosis, and diverting ileostomy at the UCLA Medical Center during the past 7 years. Seventy-seven patients underwent a second stage operation with construction of a lateral isoperistaltic ileal reservoir, 12 to 30 cm long, and closure of the ileostomy. A reservoir 10 to 15 cm long appears optimal for children, and one 20 cm long appears to function best for adults. Major complications were either related to obstruction of the reservoir outlet from leaving a rectal muscle cuff longer than 6 cm, and/or constructing the reservoir too long in the early experience (16 patients), or from cuff abscesses (four patients). Out of the 77 patients, these problems led to reservoir removal in three, temporary ileostomy in eight, and reservoir revision in 16. Persistent cuff abscess was the cause for reservoir removal in two of four patients. Continence was achieved in all patients within 2 weeks. Good to excellent results were obtained in 65 patients. At one year, 78% were completely continent during the day, 18% had minor seepage, and four per cent had occasional soiling. Frequency of defecation in patients without complications, or those surgically corrected, was seven per 24 hours within 3 months. There were no deaths. Six patients were found to have unsuspected cancer at operation. No patient experienced bladder dysfunction or abnormal sexual function. Although a technically difficult operation, the long-term results indicate that the pullthrough operation is a good alternative to proctocolectomy with ileostomy. PMID:4015218

  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-α-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. Oral mucositis.

    PubMed

    Scully, C; Sonis, S; Diz, P D

    2006-05-01

    Mucositis and xerostomia are the most common oral complications of the non-surgical therapy of cancer. Mucositis, a common sequel of radio- (DXR), chemo-(CXR) and radiochemo-therapy in patients with cancer, or patients requiring haemopoietic stem cell transplants (HSCT), has a direct and significant impact on the quality of life and cost of care, and also affects survival--because of the risk of infection. Apart from dose reduction, preventive and treatment options for mucositis are scarce, although multiple agents have been tested. Evidence suggests that cryotherapy, topical benzydamine and amifostine might provide some benefit in specific situations. The recombinant human keratinocyte growth factor Palifermin (Kepivance) was recently approved as a mucositis intervention in patients receiving conditioning regimens before HSCT for the treatment of haematological malignancies. A number of mechanistically based interventions are in various stages of development. Unfortunately, many other approaches have not been rigorously tested. This paper reviews the clinical features, prevalence, diagnosis, complications, pathogenesis, prophylaxis and management of mucositis. PMID:16700732

  4. 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

  5. Ileal impaction in 22 cows.

    PubMed

    Nuss, K; Lejeune, B; Lischer, C; Braun, U

    2006-05-01

    The clinical signs, diagnosis, treatment and outcome of 22 cows with ileal impaction were investigated using the medical records of bovine patients referred to the Department of Farm Animals, Vetsuisse Faculty, University of Zurich from 1993 to 2003. Only 15 of the cows had signs of colic, which were subtle but slowly increased in severity in some patients. The results of haematological and biochemical analyses were mildly abnormal in only few animals. There was no correlation between the duration of the disorder before admission, the severity of symptoms and the results of the haematological and biochemical analyses. Dilated loops of small intestine in the right dorsal quadrant of the abdomen could be palpated transrectally and imaged via ultrasonography. A definitive diagnosis of ileal impaction was made during exploratory laparotomy by finding the impaction and ruling out other abnormalities. In 19 cows, the obstructing food mass was easily massaged into the caecum, and in three animals an enterotomy was carried out. All cows had an uneventful recovery with no recurrence of the disorder. It is concluded that the cause of the impaction was most likely due to seasonal influences and winter-feeding with a hay based ration. The short and long-term prognosis after surgical intervention was good. PMID:16040260

  6. 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

  7. Histopathological evaluation and risk factors related to the development of pouchitis in patients with ileal pouches for ulcerative colitis

    PubMed Central

    de Godoy Arashiro, Roberta Thiery; Teixeira, Magaly Gemio; Rawet, Viviane; Quintanilha, Alina Guimares; Moura de Paula, Henrique; Silva, Adriano Zanon; Nahas, Srgio Carlos; Cecconello, Ivan

    2012-01-01

    OBJECTIVE: Many changes in mucosal morphology are observed following ileal pouch construction, including colonic metaplasia and dysplasia. Additionally, one rare but potential complication is the development of adenocarcinoma of the reservoir. The aim of this study was to evaluate the most frequently observed histopathological changes in ileal pouches and to correlate these changes with potential risk factors for complications. METHODS: A total of 41 patients were enrolled in the study and divided into the following three groups: a non-pouchitis group (group 1) (n?=?20; 8 males; mean age: 47.5 years) demonstrating optimal outcome; a pouchitis without antibiotics group (group 2) (n?=?14; 4 males; mean age: 47 years), containing individuals with pouchitis who did not receive treatment with antibiotics; and a pouchitis plus antibiotics group (group 3) (n?=?7; 3 males; mean age: 41 years), containing those patients with pouchitis who were administered antibiotics. Ileal pouch endoscopy was performed, and tissue biopsy samples were collected for histopathological analysis. RESULTS: Colonic metaplasia was found in 15 (36.6%) of the 41 patients evaluated; of these, five (25%) were from group 1, eight (57.1%) were from group 2, and two (28.6%) were from group 3. However, no correlation was established between the presence of metaplasia and pouchitis (p?=?0.17). and no differences in mucosal atrophy or the degree of chronic or acute inflammation were observed between groups 1, 2, and 3 (p>0.45). Moreover, no dysplasia or neoplastic changes were detected. However, the degree of mucosal atrophy correlated well with the time of postoperative follow-up (p?=?0.05). CONCLUSIONS: The degree of mucosal atrophy, the presence of colonic metaplasia, and the degree of acute or chronic inflammation do not appear to constitute risk factors for the development of pouchitis. Moreover, we observed that longer postoperative follow-up times were associated with greater degrees of mucosal atrophy. PMID:22892912

  8. 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 (NFκB). 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

  9. Ileal J-Pouch Perforation: Case Report.

    PubMed

    Dogan, U; Dogan, B; Habibi, M; Erol, M K; Mayir, B; Aslaner, A; Bulbuller, N

    2015-01-01

    A 34-year-old male patient who had undergone total colectomy and J-pouch ileanal anastomosis subsequent to diagnosisof familial adenomatous polyposis five years previously was admitted to the emergency room with complaints of severe abdominal pain of a four-day duration. Physical examination revealed widespread tenderness throughout the abdomen, especially in the lower quadrant. Abdominal ultrasonography revealed fluid between intestinal loops and computed tomography revealed free air and fluid in the abdomen. During laparotomy to expand the ileal J-pouch to approximately 12 cmin diameter, a 2-mm perforation was detected in the blind end of the ileal J-pouch. The perforation was repaired primarily andprotective ileostomy was performed. During postoperative endoscopy, neither obstruction nor stasis was observed, but pouchitis was observed in the ileal J-pouch. The patient was postoperatively discharged on the 20th day and followed endoscopically. The endoscopic findings were normal in the sixth month postsurgery. PMID:26158741

  10. 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 20mg/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

  11. Mucosal vaccine adjuvants update

    PubMed Central

    Lee, Shee Eun; Kim, Soo Young

    2012-01-01

    Mucosal vaccination, capable of inducing protective immune responses both in the mucosal and systemic immune compartments, has many advantages and is regarded as a blue ocean in the vaccine industry. Mucosal vaccines can offer lower costs, better accessability, needle-free delivery, and higher capacity of mass immunizations during pandemics. However, only very limited number of mucosal vaccines was approved for human use in the market yet. Generally, induction of immune responses following mucosal immunization requires the co-administration of appropriate adjuvants that can initiate and support the effective collaboration between innate and adaptive immunity. Classically, adjuvant researches were rather empirical than keenly scientific. However, during last several years, fundamental scientific achievements in innate immunity have been translated into the development of new mucosal adjuvants. This review focuses on recent developments in the concepts of adjuvants and innate immunity, mucosal immunity with special interest of vaccine development, and basic and applied researches in mucosal adjuvant. PMID:23596577

  12. IN VITRO INHIBITION OF GLUTATHIONE REDUCTASE BY ARSENOTRI-GLUTATHIONE

    EPA Science Inventory

    Arsenotriglutathione, a product of the reduction of arsenate and the complexation of arsenite by glutathione, is a mixed type inhibitor of the reduction of glutathione disulfide by purified yeast glutathione reductase or the glutathione reductase activity in rabbit erythrocyte ly...

  13. Site and mechanisms of action of kinins in rat ileal mucosa

    SciTech Connect

    Warhurst, G.; Lees, M.; Higgs, N.B.; Turnberg, L.A.

    1987-03-01

    Kinin-induced secretion in the intestine is accompanied by marked increases in mucosal adenosine 3',5'-cyclic monophosphate (cAMP) and prostanoids that undoubtedly contribute to the overall secretory responses. The authors have investigated the effects of kallidin on the phospholipase-prostanoid-cAMP pathway in whole ileal mucosa and in epithelial cells isolated from the same tissue in the rat. Kallidin (1 ..mu..M) stimulated a marked rise in PG (prostaglandin) E/sub 2/ release from the serosal surface of stripped ileal mucosa within 1-2 min, which correlated closely with the rise in mucosal short-circuit current. Mucosal cAMP levels were also increased two to threefold by kallidin. However, kinins were unable to elicit effects under the same conditions in suspensions of viable epithelial cells. PGE/sub 2/ release was unaffected by kallidin or bradykinin at concentrations up to 100 ..mu..M, whereas cAMP levels could be stimulated by forskolin and PGE/sub 2/ but not by kinin. Studies of intestinal phospholipase A/sub 2/ (PLA/sub 2/) activity also suggest a nonepithelial site for kinin action. In the intestine, PLA/sub 2/ activity was found to be concentrated within the subepithelium with significantly lower levels in the epithelium itself. In addition, kallidin was unable to influence phospholipid labeling (an indirect measure of PLA/sub 2/ activity) in cells incubated with (/sup 14/C) arachidonic acid. These studies suggest that kinins initiate increases in intestinal prostaglandin and cAMP production within the subepithelium and not by a direct action on epithelial cells.

  14. Bacterial chemotactic oligopeptides and the intestinal mucosal barrier

    SciTech Connect

    Ferry, D.M.; Butt, T.J.; Broom, M.F.; Hunter, J.; Chadwick, V.S.

    1989-07-01

    Intestinal absorption and enterohepatic circulation of N-formyl-methionyl-leucyl-/sup 125/I-tyrosine, a bioactive synthetic analog of the bacterial chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine has been investigated in the rat. In ileum and proximal and distal colon, dithiothreitol, which increases mucosal permeability, increased peptide absorption and biliary recovery fourfold, 70-fold, and 20-fold over control values, respectively. When dithiothreitol was combined with d-l-benzyl succinate, a potent inhibitor of intestinal carboxypeptidase, absorption and biliary recovery from ileal loops increased markedly to 40-fold over control, whereas there was no further increase in absorption from colon loops. There was a strong correlation between biliary N-formyl-methionyl-leucyl-/sup 125/I-tyrosine recovery and intestinal absorption of /sup 51/Cr-ethylenediaminetetraacetate, a marker of passive mucosal permeability (r = 0.97). We conclude that in the ileum both enzymic degradation and restricted mucosal permeability contribute to the intestinal barrier to luminal bacterial formyl oligopeptides. In the colon, however, enzymic mechanisms are less active and restricted mucosal permeability is the major factor. Abnormalities of the intestinal mucosal barrier to proinflammatory bacterial peptides could play a role in inflammatory disorders of the gut.

  15. Ileal follicular lymphoma with atypical endoscopic findings

    PubMed Central

    Yamada, Satoshi; Koshikawa, Yorimitsu; Minami, Naoki; Honzawa, Yusuke; Matsuura, Minoru; Nakase, Hiroshi

    2016-01-01

    A 72-year-old woman presented with symptomatic anemia without abdominal symptoms. She had no history of abdominal surgery or use of non-steroidal anti-inflammatory drugs. Enhanced computed tomography of the abdomen revealed swelling of multiple intraperitoneal lymph nodes and a high density of mesenteric adipose tissue. Fluorodeoxyglucose (FDG-) positron emission tomography showed high FDG accumulation at the intraperitoneal lymph nodes. Double-balloon enteroscopy detected severe stenosis with an annular ulcer in the lower ileum. She was diagnosed with ileal follicular lymphoma based on histologic examination and fluorescence in situ hybridization analysis of the biopsy specimen. The ileal ulcer was successfully treated by chemotherapy with rituximab and bendamustine for 1 year. We strongly recommend consideration of gastrointestinal follicular lymphoma in the differential diagnosis of annular ulcers in the small intestine.

  16. Ileoileal intussusception secondary to an ileal fibroma.

    PubMed

    Chelimilla, Haritha; Ihimoyan, Ariyo; Carvajal, Simeon; Bhavna, Balar

    2012-09-01

    Intussusception is defined as the telescoping of a segment of the gastrointestinal tract (intussusceptum) into an immediately adjacent distal bowel (intussuscipiens). Intussusception is a relatively rare cause of intestinal obstruction in adults. Unlike in children, a lead point is present in 90% of adult cases. The most common causes of small bowel intussusception are benign, usually hamartomas, lipomas, inflammatory polyps, adenomas and leiomyomas, in contrast to the large intestine where malignant tumors, usually adenocarcinomas, are more common. The clinical presentation of adult intussusception is non-specific with variable manifestations, predominantly those of intestinal obstruction, often making the diagnosis a challenge. The onset of symptoms may be acute, intermittent or chronic. We present a rare case of an ileal fibroma presenting with intussusception. A 43-year-old woman presented to our outpatient clinic with a history of recurrent abdominal pain. The clinical presentation and CT scan findings led to the diagnosis of ileoileal intussusception. Subsequently she underwent laparotomy which revealed an ileal fibroma as the lead point of the intussusception. Surgical exploration remains essential for diagnosis and treatment since in the majority of cases a pathologic lead point is identified. Ileal fibroma is an uncommon benign neoplasm of the small bowel and must be considered in the differential diagnosis for small bowel intussusception. PMID:23275765

  17. The Analysis of Factors Associated with Progression of Isolated Terminal Ileal Lesions

    PubMed Central

    Fangbin, Zhang; Weiwei, Hao; Wugan, Zhao; Cong, Zheng; Yanjun, Chu; Feng, Xu

    2014-01-01

    Objective To assess the factors associated with the progression of isolated terminal ileal lesions (ITILs) at colonoscopy in Chinese patients. Methods Patients diagnosed with ITILs were enrolled. The ileoscopy was performed by two experienced gastroenterologists every 52 weeks. A logistic regression analysis was used to elucidate the factors associated with Crohn's disease (CD) and mucosal healing. A log rank test was used to assess the differences of the cumulative proportion of CD and mucosal healing in different groups at different times. Results (1) A total of 34 patients were included and no patient had taken nonsteroidal anti-inflammatory drug in the last 6 months; eight (23.5%) patients had a clinical diagnosis of CD, 14 (41.2%) patients achieved mucosal healing, and 12 (35.3%) patients showed no significant changes in the lesions at last follow-up. (2) The logistic regression analysis showed that only abdominal pain was a factor in the ITIL disease outcomes. (3) The cumulative proportion of CD in the abdominal pain group after 3 years was statistically higher than that in the non-abdominal pain group (42.7% vs. 6.2%, ?2?=?10.129, P?=?0.001). However, the cumulative proportion of mucosal healing in the non-abdominal pain group was statistically higher than that in the abdominal pain group (73.3% vs. 5.6%, ?2?=?5.225, P?=?0.022). (4) The numbers of lesions observed on the initial colonoscopy exams and the initial histologic findings were not related to the ITIL disease outcomes. Conclusions Clinical symptoms may be related to ITIL disease outcomes. Patients with abdominal pain had a high likelihood of CD, whereas those without abdominal pain had a high likelihood of mucosal healing. PMID:24625578

  18. Oral Nucleotides Only Minimally Improve 5-Fluorouracil-Induced Mucositis in Rats.

    PubMed

    Mashtoub, Suzanne; Feo, Benjamin; Whittaker, Alexandra L; Lymn, Kerry A; Martinez-Puig, Daniel; Howarth, Gordon S

    2015-01-01

    Chemotherapy-induced mucositis is characterized by inflammation and ulceration of the intestinal mucosa, compromising intestinal function. Exogenous nucleotides have been reported to repair the mucosa. The nucleotide preparation, Nucleoforce F0328 (Nucleoforce), was investigated for its potential to ameliorate intestinal mucositis in rats. Female Dark Agouti rats (n = 8/group) were gavaged once daily with Nucleoforce (175 mg/kg) or water from Days 0 to 8 and injected (i.p.) with 5-fluorouracil (5-FU; 150 mg/kg) or saline on Day 5. Histological parameters (disease severity, crypt depth, and villus height measurements) and myeloperoxidase activity were quantified. P < 0.05 was considered significant. Jejunal and ileal histological disease severity scores were significantly increased by 5-FU, compared to normal controls (P < 0.05). Nucleoforce treatment in 5-FU-injected rats significantly reduced jejunal and ileal disease severity compared to 5-FU controls (P < 0.05). In 5-FU-injected rats, jejunal and ileal villus heights and crypt depths were significantly decreased compared to 5-FU controls, with no additional Nucleoforce effect (P > 0.05). Intestinal myeloperoxidase activity was significantly elevated by 5-FU (8.8-fold), compared to normal controls (P < 0.05), which was not normalized by Nucleoforce treatment (P > 0.05). Nucleoforce only partially improved parameters associated with experimentally-induced mucositis. Future studies could investigate increased concentrations, more frequent administration, or protective microencapsulation delivery methods, to increase bioavailability. PMID:26284427

  19. Why mucosal health?

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. Radiation Induced Oral Mucositis

    PubMed Central

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

    2009-01-01

    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

  1. 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

  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. Strategies for mucosal vaccine development.

    PubMed

    Boyaka, P N; Marinaro, M; Vancott, J L; Takahashi, I; Fujihashi, K; Yamamoto, M; van Ginkel, F W; Jackson, R J; Kiyono, H; McGhee, J R

    1999-04-01

    Vaccines able to induce both secretory IgA for protection of mucosal surfaces and systemic immunity to pathogens invading the host are of great interest in the war against infectious diseases. Mucosal vaccines trigger immune cells in mucosal inductive sites and thus can induce immunity in both the mucosal and systemic compartments. This review presents a critical survey of adjuvants and delivery systems currently being tested for mucosal immunization. A better understanding of cellular and molecular factors involved in the regulation of mucosal immunity will help in the design of safer mucosal vaccines to elicit the appropriate protective immune response to a given pathogen. PMID:10344675

  4. Mucosal Health in Aquaculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Abstract The mucosal surfaces (skin, gill, and intestine) constitute the first line of defense against pathogen invasion while simultaneously carrying out a diverse array of other critical physiological processes, including nutrient absorption, osmoregulation, and waste excretion. Aquaculture specie...

  5. Genotyping of mucosal melanoma.

    PubMed

    Si, Lu; Wang, Xuan; Guo, Jun

    2014-09-01

    Mucosal melanoma is rare and associated with extremely poor prognosis. Mucosal melanoma has historically been refractory to traditional therapeutic approaches. Recently molecularly based targeted drugs show great success in melanoma. The success of these drug strategies can be partially attributed to the identification of the genetic alterations responsible for the development and progression of metastatic melanoma. This review will focus on genes involved in two major mucosal melanoma-related signaling pathways, the RAS/RAF/mitogen activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinases (PI3K)-AKT pathway, and detail the current understanding of their roles in melanoma progression. Additional mutations in key genes, such as KIT, GNAQ and MITF, in mucosal melanoma will also be introduced. Finally, an overview of the current targeted therapy landscape will be provided. PMID:25841460

  6. Chitosan for mucosal vaccination.

    PubMed

    van der Lubben, I M; Verhoef, J C; Borchard, G; Junginger, H E

    2001-11-01

    The striking advantage of mucosal vaccination is the production of local antibodies at the sites where pathogens enter the body. Because vaccines alone are not sufficiently taken up after mucosal administration, they need to be co-administered with penetration enhancers, adjuvants or encapsulated in particles. Chitosan easily forms microparticles and nanoparticles which encapsulate large amounts of antigens such as ovalbumin, diphtheria toxoid or tetanus toxoid. It has been shown that ovalbumin loaded chitosan microparticles are taken up by the Peyer's patches of the gut associated lymphoid tissue (GALT). This unique uptake demonstrates that chitosan particulate drug carrier systems are promising candidates for oral vaccination. Additionally, after co-administering chitosan with antigens in nasal vaccination studies, a strong enhancement of both mucosal and systemic immune responses is observed. This makes chitosan very suitable for nasal vaccine delivery. In conclusion, chitosan particles, powders and solutions are promising candidates for mucosal vaccine delivery. Mucosal vaccination not only reduces costs and increases patient compliance, but also complicates the invasion of pathogens through mucosal sites. PMID:11718937

  7. Delayed complication of pelvic lymphocele: Ileal conduit obstruction

    PubMed Central

    Bankar, Sanket S.; Bakshi, Ganesh K.; Prakash, Gagan; Sable, Nilesh P.

    2015-01-01

    Radical cystectomy is the standard treatment for muscle invasive bladder cancer. Lymphocele is a common sequalae of pelvic lymphadenectomy. We report an unusual presentation of pelvic lymphocele developing after radical cystectomy reconstructed with an ileal conduit where the patient developed obstruction of the ileal conduit loop due to external pressure of the lymphocele. Catheter drainage of the conduit relieved the symptoms and a computerized tomography scan showed a large lymphocele causing acute angulation and resultant obstruction of the ileal conduit. The patient was treated with percutaneous drainage of the lymphocele and remains symptom-free on follow-up at 1 year. PMID:26166973

  8. Delayed complication of pelvic lymphocele: Ileal conduit obstruction.

    PubMed

    Bankar, Sanket S; Bakshi, Ganesh K; Prakash, Gagan; Sable, Nilesh P

    2015-01-01

    Radical cystectomy is the standard treatment for muscle invasive bladder cancer. Lymphocele is a common sequalae of pelvic lymphadenectomy. We report an unusual presentation of pelvic lymphocele developing after radical cystectomy reconstructed with an ileal conduit where the patient developed obstruction of the ileal conduit loop due to external pressure of the lymphocele. Catheter drainage of the conduit relieved the symptoms and a computerized tomography scan showed a large lymphocele causing acute angulation and resultant obstruction of the ileal conduit. The patient was treated with percutaneous drainage of the lymphocele and remains symptom-free on follow-up at 1 year. PMID:26166973

  9. Ileal Fecaloma Presenting with Small Bowel Obstruction

    PubMed Central

    Yoo, Ha Yeong; Park, Hye Won; Chang, Seong-Hwan

    2015-01-01

    A fecaloma refers to a mass of accumulated feces that is much harder than a mass associated with fecal impaction. Fecalomas are usually found in the rectosigmoid area. A 10-year-old male with chronic constipation was admitted because of increasing abdominal pain. An abdominal computed tomography scan and a simple abdominal x-ray revealed rapidly evolving mechanical obstruction in the small intestine. Most of the fecalomas are successfully treated by conservative methods such as laxatives, enemas and rectal evacuation. When conservative treatments have failed, surgical intervention may be needed. In this case, an emergency operation was performed and a 432.5 cm fecaloma was found in the distal ileum. We thus report a case of ileal fecaloma inducing small bowel obstruction in a patient with chronic constipation, who required surgical intervention. When symptoms of acute small intestinal obstruction develop in a patient with chronic constipation, a fecaloma should be considered in differential diagnosis. PMID:26473140

  10. 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

  11. Reproduction of porcine proliferative enteropathy with pure cultures of ileal symbiont intracellularis.

    PubMed Central

    McOrist, S; Jasni, S; Mackie, R A; MacIntyre, N; Neef, N; Lawson, G H

    1993-01-01

    Porcine proliferative enteropathy is consistently associated with the presence of intracellular curved bacteria in epithelial cells in affected portions of intestine. Two strains of these intracellular bacteria were cultured in a cell culture system with rat enterocytes (IEC-18) and passaged several times and used as oral inocula for 14 gnotobiotic and 8 conventional pigs. DNA and immunological studies had identified these bacteria as belonging to a new taxon, Ileal symbiont (IS) intracellularis. Conventional pigs dosed with approximately 3.7 x 10(6) of these organisms passaged six times in cell culture developed severe lesions of proliferative enteropathy in the ileum. Other conventional pigs dosed with a lower titer or with organisms passaged 13 times developed moderate and minor lesions, respectively. All gnotobiotic pigs dosed with organisms failed to develop lesions. Control pigs, eight conventional and two gnotobiotic, dosed with diluent, uninfected cell material or left undosed failed to develop lesions also. Reisolation of IS intracellularis and demonstration of the organism in mucosal and fecal samples only occurred in conventional pigs dosed with organisms. Gnotobiotic pigs lacking a normal intestinal flora have not been shown to be colonized by the organism. Seroconversion to IS intracellularis or mucosal infiltration by inflammatory cells was not observed in experimentally affected pigs, confirming the weak immune response characteristic of the natural disease. These results support the identification of IS intracellularis as an etiological agent of proliferative enteropathy in pigs. Images PMID:8406817

  12. 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 g 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

  13. Vaccines against mucosal infections.

    PubMed

    Holmgren, Jan; Svennerholm, Ann-Mari

    2012-06-01

    There remains a great need to develop vaccines against many of the pathogens that infect mucosal tissues or have a mucosal port of entry. Parenteral vaccination may protect in some instances, but usually a mucosal vaccination route is necessary. Mucosal vaccines also have logistic advantages over injectable vaccines by being easier to administer, having less risk of transmitting infections and potentially being easier to manufacture. Still, however, only relatively few vaccines for human use are available: oral vaccines against cholera, typhoid, polio, and rotavirus, and a nasal vaccine against influenza. For polio, typhoid and influenza, in which the pathogens reach the blood stream, there is also an injectable vaccine alternative. A problem with available oral live vaccines is their reduced immunogenicity when used in developing countries; for instance, the efficacy of rotavirus vaccines correlates closely with the national per capita income. Research is needed to define the impact of factors such as malnutrition, aberrant intestinal microflora, concomitant infections, and preexisting immunity as well as of host genetic factors on the immunogenicity of these vaccines. PMID:22580196

  14. Membrane accessibility of glutathione.

    PubMed

    Garcia, Alvaro; Eljack, Nasma D; Sani, Marc-Antoine; Separovic, Frances; Rasmussen, Helge H; Kopec, Wojciech; Khandelia, Himanshu; Cornelius, Flemming; Clarke, Ronald J

    2015-10-01

    Regulation of the ion pumping activity of the Na+,K+-ATPase is crucial to the survival of animal cells. Recent evidence has suggested that the activity of the enzyme could be controlled by glutathionylation of cysteine residue 45 of the β-subunit. Crystal structures so far available indicate that this cysteine is in a transmembrane domain of the protein. Here we have analysed via fluorescence and NMR spectroscopy as well as molecular dynamics simulations whether glutathione is able to penetrate into the interior of a lipid membrane. No evidence for any penetration of glutathione into the membrane was found. Therefore, the most likely mechanism whereby the cysteine residue could become glutathionylated is via a loosening of the α-β subunit association, creating a hydrophilic passageway between them to allow access of glutathione to the cysteine residue. By such a mechanism, glutathionylation of the protein would be expected to anchor the modified cysteine residue in a hydrophilic environment, inhibiting further motion of the β-subunit during the enzyme's catalytic cycle and suppressing enzymatic activity, as has been experimentally observed. The results obtained, therefore, suggest a possible structural mechanism of how the Na+,K+-ATPase could be regulated by glutathione. PMID:26232559

  15. Open cystolithotomy for very large calculi in a Studer ileal neobladder.

    PubMed

    Ouellet, Simon; Jeldres, Claudio; Simard, Hugo; Sabbagh, Robert; Carmel, Michel

    2015-12-01

    Orthotopic ileal neobladder has been frequently performed as urinary diversion after cystectomy over the last decades. We report an unusual complication of very large calculi in a Studer ileal neobladder. Due to its size, open cystolithotomy was performed. PMID:26688144

  16. TAK1 is a key modulator of the profibrogenic phenotype of human ileal myofibroblasts in Crohn's disease.

    PubMed

    Grillo, Alessia Rosaria; Scarpa, Melania; D'Inc, Renata; Brun, Paola; Scarpa, Marco; Porzionato, Andrea; De Caro, Raffaele; Martines, Diego; Buda, Andrea; Angriman, Imerio; Pal, Giorgio; Sturniolo, Giacomo Carlo; Castagliuolo, Ignazio

    2015-09-15

    Transforming growth factor (TGF)-?-activated kinase 1 (TAK1) signaling can mediate inflammatory responses as well as tissue remodeling. Intestinal mucosal myofibroblast (IMF) activation drives gut fibrosis in Crohn's disease (CD); however, the molecular pathways involved are largely unknown. Thus we investigated the yet-unknown expression and function of TAK1 in human CD-associated fibrosis. Ileal surgical specimens, ileal biopsies, and IMF isolated from controls and CD patients were analyzed for TAK1 and its active phosphorylated form (pTAK1) by Western blotting, immunohistochemistry, and real-time quantitative PCR. TAK1 pharmacological inhibition and silencing were used to assess its role in collagen and inflammatory cytokine synthesis in IMF. TAK1 and pTAK1 levels increased in ileum specimens from CD patients compared with controls and correlated to tissue fibrosis. Similarly, TAK1 mRNA in ileal biopsies of CD patients correlated with fibrogenic marker expression but not inflammatory cytokines. CD-derived IMF showed higher TAK1 and pTAK1 expression associated with increased collagen1(?)1 mRNA levels compared with control IMF. TGF-?1 promoted pTAK1 nuclear translocation and collagen synthesis. TAK1 inhibition or silencing significantly reduced TGF-?1-stimulated collagen production and normalized the profibrogenic phenotype of CD-derived IMF. Taken together, these data suggest that TAK1 activation and nuclear translocation induce and maintain a fibrogenic phenotype in the IMF. Thus the TAK1 signaling pathway may represent a suitable target to design new, antifibrotic therapies. PMID:26185333

  17. Histopathological study of colo-ileal carcinoma

    PubMed Central

    MATSUKUMA, SUSUMU; OKADA, KENJI; TAKEO, HIROAKI; SATO, KIMIYA

    2011-01-01

    Cases of colo-ileal carcinoma (CIC), defined as intestinal carcinoma involving the right-sided colon and the ileum, are rarely encountered. The aim of this study was to elucidate the clinicopathological characteristics, which have been poorly understood, in such cases. A total of 16 CICs were examined histologically and immunohistochemically. Microsatellite instability-related histology was also evaluated according to previously published models, such as MsPath and PREDICT. CICs included 14 adenocarcinomas and 2 mucinous adenocarcinomas. The CICs showed focal or diffuse cytokeratin 20 expression and 7 CICs showed focal cytokeratin 7 co-expression. MsPath and PREDICT scores ranged from 1.6 to 6.6 (mean, 3.14) and from 1.6 to 7.8 (mean, 3.86), respectively. Three CICs showed loss of MLH1 immunoreactivity. Prominent neutrophilia and cancerous lymphangiosis in Peyers patches (CLPP) were found in 8 cases (50%) and in 3 cases (18.8%), respectively. Neither variable was associated with parameters such as gender, tumor size or poor prognosis. However, the PREDICT score in prominently neutrophilic CICs was significantly higher than that in CICs with non-prominent neutrophilia (P=0.004). Patients with CLPP-positive CICs were significantly younger than those with CLPP-negative CICs (P=0.031). This study showed that almost all CICs originate from the right-sided colon with possible high levels of microsatellite instability. Prominent neutrophilia may be an additional histological indicator for microsatellite instability. Prognosis-independent CLPP occasionally occurs in younger patients with CICs. PMID:22740977

  18. Contrast Enhanced Abdominal Ultrasound in the Assessment of Ileal Inflammation in Crohn’s Disease: A Comparison with MR Enterography

    PubMed Central

    Horjus Talabur Horje, C. S.; Roovers, L.; Groenen, M. J. M.; Wahab, P. J.

    2015-01-01

    Background and Aims To prospectively examine the feasibility and accuracy of Contrast Enhanced Ultrasound (CEUS) in the assessment of Crohn’s disease (CD) activity in the terminal ileum in comparison to Magnetic Resonance Enterography (MRE), using endoscopy as a reference standard. Methods 105 consecutive patients with alleged clinically active CD were assessed by MRE and CEUS. CEUS of the terminal ileum was performed using an intravenous microbubble contrast enhancer. Accuracy values of CEUS and MRE for the presence of active terminal ileitis were evaluated using the Receiver Operating Characteristic method, using endoscopic findings as a reference standard. Sensitivity and specificity values of MRE and CEUS were compared by the McNemar test. Results CEUS was feasible in 98% of patients, MRE in all. Optimal diagnostic accuracy in CEUS was obtained at a peak intensity value of 10%, showing 100% sensitivity, 92% specificity and an accuracy of 99% in demonstrating ileal mucosal inflammation. For MRE, overall sensitivity, specificity and accuracy were, 87%, 100%, and 88%, respectively. CEUS and MRE were highly correlated in assessing length and wall thickness of the terminal ileum. CEUS identified 11 of 16 MRE-detected strictures, but no fistulae. Conclusion The accuracy of CEUS is comparable to that of MRE in the assessment of active, uncomplicated terminal ileal CD and therefore a valuable bedside alternative to MRE in the follow-up of these patients. PMID:26322970

  19. Optimizing efficacy of mucosal vaccines.

    PubMed

    Gebril, Ayman; Alsaadi, Manal; Acevedo, Reinaldo; Mullen, Alexander B; Ferro, Valerie A

    2012-09-01

    In general, there are only a few vaccines administered via mucosal routes, as the mucosal immune system presents numerous hurdles, including diversity in mucosal surface structure, complexity in immune cell interaction and limitations in experimental methodology. This therefore necessitates a range of strategies to be used for each target area. With reference to the three main routes of delivery and associated mucosal surfaces (oral/intestinal, nasal/respiratory and female genital tract), this review examines how coadministration of immune-stimulatory molecules, adjuvants, delivery systems and mucoadhesives are used to improve mucosal vaccine efficacy. Key considerations to the development of next-generation mucosal vaccines include improved efficacy and safety, technological advancements in medical devices to enable convenience and better administration, as well as reduced manufacturing costs. PMID:23151169

  20. Hemiresective reconstruction of a redundant ileal conduit with severe bilateral ileal conduit-ureteral re fl ux.

    PubMed

    Fujimura, Tetsuya; Minowada, Shigeru; Kishi, Hiroichi; Hamasaki, Kimihisa; Saito, Kiyoshi; Kitamura, Tadaichi

    2005-10-01

    A 58-year-old man was referred to our hospital with high fever and anuria. Since undergoing a total pelvic exenteration due to bladder-invasive sigmoid colon cancer, urinary tract infections had frequently occurred. We treated with the construction of a bilateral percutaneous nephrostomy (PCN), and chemotherapy. Although we replaced the PCN with a single J ureteral catheter after an improvement of infection, urinary infection recurred because of an obstruction of the catheter. Urological examinations showed that an ileal conduit-ureteral reflux caused by kinking of the ileal loop was the reason why frequent pyelonephritis occurred. We decided to resect the proximal segment to improve conduit-ureteral reflux for the resistant pyelonephritis. After the surgery, the excretory urogram showed improvement and the urinary retention at the ileal conduit disappeared. Three years after the operation, renal function has been stable without episodes of pyelonephritis. Here we report a case of open repair surgery of an ileal conduit in a patient with severe urinary infection. PMID:16323988

  1. Maintenance of superior mesenteric arterial perfusion prevents increased intestinal mucosal permeability in endotoxic pigs

    SciTech Connect

    Fink, M.P.; Kaups, K.L.; Wang, H.L.; Rothschild, H.R. )

    1991-08-01

    Lipopolysaccharide increases intestinal mucosal permeability to hydrophilic compounds such as chromium 51-labeled edetate (51Cr-EDTA). The authors sought to determine whether this phenomenon is partly mediated by lipopolysaccharide-induced mesenteric hypoperfusion. They assessed permeability in an isolated segment of ileum by measuring plasma-to-lumen clearances (C) for two probes, 51Cr-EDTA and urea, and expressing the results as a ratio (CEDTA/CUREA). In control pigs (n = 6) resuscitated with Ringer's lactate (RL), mucosal permeability was unchanged during the 210-minute period of observation. In pigs (n = 7) infused with lipopolysaccharide (50 micrograms/kg) and similarly resuscitated with RL, mesenteric perfusion (Qsma) decreased significantly and permeability increased progressively and significantly. When endotoxic pigs (n = 6) were resuscitated with a regimen (RL plus hetastarch plus dobutamine) that preserved normal Qsma, lipopolysaccharide-induced mucosal hyperpermeability was prevented. Resuscitation of endotoxic pigs (n = 6) with RL plus hetastarch provided intermediate protection against both mesenteric hypoperfusion and increased permeability. These data suggest that diminished Qsma contributes to impaired ileal mucosal barrier function in experimental endotoxicosis.

  2. Glutathione and apoptosis.

    PubMed

    Circu, Magdalena L; Aw, Tak Yee

    2008-08-01

    Apoptosis or programmed cell death represents a physiologically conserved mechanism of cell death that is pivotal in normal development and tissue homeostasis in all organisms. As a key modulator of cell functions, the most abundant non-protein thiol, glutathione (GSH), has important roles in cellular defense against oxidant aggression, redox regulation of proteins thiols and maintaining redox homeostasis that is critical for proper function of cellular processes, including apoptosis. Thus, a shift in the cellular GSH-to-GSSG redox balance in favour of the oxidized species, GSSG, constitutes an important signal that could decide the fate of a cell. The current review will focus on three main areas: (1) general description of cellular apoptotic pathways, (2) cellular compartmentation of GSH and the contribution of mitochondrial GSH and redox proteins to apoptotic signalling and (3) role of redox mechanisms in the initiation and execution phases of apoptosis. PMID:18671159

  3. Glutathione and apoptosis

    PubMed Central

    Circu, Magdalena L.; Yee Aw, Tak

    2011-01-01

    Apoptosis or programmed cell death represents a physiologically conserved mechanism of cell death that is pivotal in normal development and tissue homeostasis in all organisms. As a key modulator of cell functions, the most abundant non-protein thiol, glutathione (GSH), has important roles in cellular defense against oxidant aggression, redox regulation of proteins thiols and maintaining redox homeostasis that is critical for proper function of cellular processes, including apoptosis. Thus, a shift in the cellular GSH-to-GSSG redox balance in favour of the oxidized species, GSSG, constitutes an important signal that could decide the fate of a cell. The current review will focus on three main areas: (1) general description of cellular apoptotic pathways, (2) cellular compartmentation of GSH and the contribution of mitochondrial GSH and redox proteins to apoptotic signalling and (3) role of redox mechanisms in the initiation and execution phases of apoptosis. PMID:18671159

  4. 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

  5. Glutathione transferases and neurodegenerative diseases.

    PubMed

    Mazzetti, Anna Paola; Fiorile, Maria Carmela; Primavera, Alessandra; Lo Bello, Mario

    2015-03-01

    There is substantial agreement that the unbalance between oxidant and antioxidant species may affect the onset and/or the course of a number of common diseases including Parkinson's and Alzheimer's diseases. Many studies suggest a crucial role for oxidative stress in the first phase of aging, or in the pathogenesis of various diseases including neurological ones. Particularly, the role exerted by glutathione and glutathione-related enzymes (Glutathione Transferases) in the nervous system appears more relevant, this latter tissue being much more vulnerable to toxins and oxidative stress than other tissues such as liver, kidney or muscle. The present review addresses the question by focusing on the results obtained by specimens from patients or by in vitro studies using cells or animal models related to Parkinson's and Alzheimer's diseases. In general, there is an association between glutathione depletion and Parkinson's or Alzheimer's disease. In addition, a significant decrease of glutathione transferase activity in selected areas of brain and in ventricular cerebrospinal fluid was found. For some glutathione transferase genes there is also a correlation between polymorphisms and onset/outcome of neurodegenerative diseases. Thus, there is a general agreement about the protective effect exerted by glutathione and glutathione transferases but no clear answer about the mechanisms underlying this crucial role in the insurgence of neurodegenerative diseases. PMID:25661512

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

    PubMed

    Xanthis, A; Hakeem, A; Safranek, P

    2015-04-01

    Complications from a Meckel's diverticulum include diverticulitis, bleeding, intussusception, bowel obstruction, a volvulus, a vesicodiverticular fistula, perforation or very rarely as a tumour. We report a case where a Meckel's diverticulum presented with a terminal ileal volvulus in a 32-year-old man without the presence of a typical vitelline band or axial torsion of the diverticulum causing the volvulus. It was successfully managed laparoscopically. PMID:26263827

  7. Ileal microbiota composition of broilers fed various commercial diet compositions.

    PubMed

    van der Hoeven-Hangoor, E; van der Vossen, J M B M; Schuren, F H J; Verstegen, M W A; de Oliveira, J E; Montijn, R C; Hendriks, W H

    2013-10-01

    Microbiota plays a role in the release and absorption of nutrients from feed components, thereby affecting digesta composition and moisture content of the excreta. The objective of the current study was to determine the effects of 5 different diets varying in ingredients (medium-chain fatty acids, nonstarch polysaccharides, and starch) on the microbiota composition of ileal digesta of broiler chickens and excreta DM content. Each treatment was repeated 6 times in cages each containing 18 Ross 308 broilers, with growth performance measured from 0 to 34 d of age and excreta DM and ileal microbiota composition analyzed at 34 d of age. Microbiota composition was evaluated using a novel ribosomal RNA microarray technology containing 370 different probes covering various genera, groups of microbial species, and individual species of the chicken gut microbiota, of which 321 had a signal above the background threshold. Replacing part of the animal fat and soybean oil in the wheat-based diet with medium-chain fatty acids (MCFA; 0.3% C10 and 2.7% C12) improved feed efficiency compared with the other dietary treatments. This coincided with a suppression of gram-positive bacteria belonging to the phylum of the Firmicutes, including Lactobacillus species, and species belonging to the family of the Enterococcaceae and Micrococcaceae, whereas the gram-negative bacteria belonging to the family of the Enterobacteriaceae were promoted. None of the other diets used in the present study notably changed the ileal digesta bacteria composition. Excreta DM content was not affected by dietary treatment. The variation between individual birds per dietary treatment was more pronounced than variation caused by feed composition, with the exception of the digesta microbiota of the birds fed the MCFA diet. It is concluded that a diet with MCFA significantly changes the ileal microbiota composition, whereas the effect of the other diets on the composition of the microbiota and excreta DM content is small in broiler chickens. PMID:24046419

  8. Emu oil expedites small intestinal repair following 5-fluorouracil-induced mucositis in rats.

    PubMed

    Mashtoub, Suzanne; Tran, Cuong D; Howarth, Gordon S

    2013-11-01

    Mucositis resulting from cancer chemotherapy is characterized by intestinal inflammation and ulceration. Previously, emu oil (EO) improved intestinal architecture (Br J Nutr, 2010) in a rat model of chemotherapy-induced mucositis. We investigated EO for its further potential to promote intestinal repair in this mucositis model. Female Dark Agouti rats (n?=?8/group) were gavaged with water, olive oil (OO) or EO once daily (1?mL), injected with 5-fluorouracil (5-FU) or saline on day 5 and euthanized on day 8, 9, 10 or 11. Intestinal villus height (VH) and crypt depth (CD), neutral mucin-secreting goblet cell (GC) count, myeloperoxidase (MPO) activity and selected cytokines were quantified; P?ileal GC on days 10 and 11 compared to 5-FU controls. MPO activity was significantly increased in jejunum (days 8 and 9) and ileum (day 8) following 5-FU injection, compared to normal controls (P?ileal MPO on day 8. Cytokine levels were not significantly affected by either oil or 5-FU administration at the day 8 time point. Promotion of repair from injury could represent a new mechanism of action for EO, suggesting potential as an adjunct to conventional treatment approaches for cancer management. PMID:24047797

  9. Glutathione specifically labeled with isotopes

    SciTech Connect

    Murata, K.; Abbott, W.A.; Bridges, R.J.; Meister, A.

    1985-10-01

    A procedure for synthesis of glutathione selectivity labeled with isotopes is described. A strain of Escherichia coli enriched in its content of gamma-glutamylcysteine synthetase and glutathione synthetase by recombinant DNA techniques is immobilized in a carrageenan matrix and treated with toluene to render the cells more permeable to the substrates. The immobilized cell matrix is incubated with a mixture containing the appropriately labeled amino acid, the other amino acid constituents of glutathione, ATP, and acetylphosphate. The radiolabeled product is isolated by column chromatography.

  10. Glutathione and mitochondria

    PubMed Central

    Ribas, Vicent; Garca-Ruiz, Carmen; Fernndez-Checa, Jos 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 Alzheimers disease. PMID:25024695

  11. REGULATION OF GLUTATHIONE SYNTHESIS

    PubMed Central

    Lu, Shelly C.

    2009-01-01

    Glutathione (GSH) is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and 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 availability of cysteine, the sulfur amino acid precursor, and the activity of the rate-limiting enzyme, glutamate cysteine ligase (GCL). GCL is composed for a catalytic (GCLC) and modifier (GCLM) subunit and they are regulated at multiple levels and at times differentially. The second enzyme of GSH synthesis, GSH synthase (GS) is also regulated in a coordinated manner as GCL subunits and its up-regulation can further enhance the capacity of the cell to synthesize GSH. Oxidative stress is well known to induce the expression of GSH synthetic enzymes. Key transcription factors identified thus far include Nrf2/Nrf1 via the antioxidant response element (ARE), activator protein-1 (AP-1) and nuclear factor κ B (NFκB). Dysregulation of GSH synthesis is increasingly being recognized as contributing to the pathogenesis of many pathological conditions. These include diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells. Manipulation of the GSH synthetic capacity is an important target in the treatment of many of these disorders. PMID:18601945

  12. 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 SpragueDawley 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

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

    PubMed

    Sukhotnik, Igor; Pollak, Yulia; Coran, Arnold G; Pilatov, Janna; Bejar, Jacob; Mogilner, Jorge G; Berkowitz, Drora

    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

  14. Vaccination strategies to promote mucosal antibody responses.

    PubMed

    Chen, Kang; Cerutti, Andrea

    2010-10-29

    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. We review the important cellular interactions and molecular pathways underlying the induction and regulation of mucosal antibody responses and discuss their implications on mucosal vaccination. PMID:21029959

  15. Hepatic glutathione and glutathione S-conjugate transport mechanisms.

    PubMed Central

    Lee, T. K.; Li, L.; Ballatori, N.

    1997-01-01

    Glutathione (GSH) plays a critical role in many cellular processes, including the metabolism and detoxification of oxidants, metals, and other reactive electrophilic compounds of both endogenous and exogenous origin. Because the liver is a major site of GSH and glutathione S-conjugate biosynthesis and export, significant effort has been devoted to characterizing liver cell sinusoidal and canalicular membrane transporters for these compounds. Glutathione S-conjugates synthesized in the liver are secreted preferentially into bile, and recent studies in isolated canalicular membrane vesicles indicate that there are multiple transport mechanisms for these conjugates, including those that are energized by ATP hydrolysis and those that may be driven by the electrochemical gradient. Glutathione S-conjugates that are relatively hydrophobic or have a bulky S-substituent are good substrates for the canalicular ATP-dependent transporter mrp2 (multidrug resistance-associated protein 2, also called cMOAT, the canalicular multispecific organic anion transporter, or cMrp, the canalicular isoform of mrp). In contrast with the glutathione S-conjugates, hepatic GSH is released into both blood and bile. GSH transport across both of these membrane domains is of low affinity and is energized by the electrochemical potential. Recent reports describe two candidate GSH transport proteins for the canalicular and sinusoidal membranes (RcGshT and RsGshT, respectively); however, some concerns have been raised regarding these studies. Additional work is needed to characterize GSH transporters at the functional and molecular level. PMID:9626749

  16. 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

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

    PubMed

    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

  18. 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 68Ga-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

  19. Pulmonary and ileal tuberculosis presenting as Fever of undetermined origin.

    PubMed

    Surewad, Gajanan; Lobo, Ivona; Shanbag, Preeti

    2014-10-01

    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

  20. AB058. Clinic practice of the laparoscopic ileal bladder augmentation

    PubMed Central

    Xu, Zhihui; Qi, Xiaolong; Liu, Feng; Zhang, Dahong

    2015-01-01

    Objective To investigate the efficacy and safety of laparoscopic ileal bladder augmentation in treating patients with low compliant bladder dysfunction. Methods From June 2011 to December 2013, 22 patients with low compliant bladder dysfunction were enrolled and received laparoscopic ileal bladder expanding. Postoperative complications, renal function, hydronephrosis, glomerular filtration rate, urodynamics parameters and quality of daily life were evaluated. Results The laparoscopic ileal bladder expanding were all successful. The average operation time was (105.016.7) min, the bleeding volume was (90.026.0) mL, the recovery time of intestinal function was (2.50.7) days, the hospitalization time was (15.04.2) days. All the patients had no serious complications, such as ileum anastomotic fistula, intestinal obstruction and abdominal infection or sepsis. Among them, 17 patients were followed up for more than 12 months. Compared with the preoperative condition, the average bladder capacity and bladder compliance were significantly increased from (103.038.2) cmH2O to (403.045.8) cmH2O, and from (9.63.1) to (38.14.4) mL/cmH2O (P<0.001), respectively. And the average bladder pressure at the end of filling phrase of cystometry were significantly decreased from (45.315.8) cmH2O to (16.56.4) cmH2O (P<0.001). The preoperative and postoperative serum creatinine level were (183.532.2) ?mol/L and (12028.4) ?mol/L (P<0.001), respectively. The preoperative and postoperative total glomerular filtration rate were (40.025.5) mL/min/1.73m2 and (62.028.6) mL/min/1.73m2 (P<0.05), respectively. Conclusions The operation of laparoscopic ileal bladder expanding is feasible and security, with the advantages of little injury, less bleeding, quicker recovery of intestinal function and less postoperative complications. The bladder function was obviously improved after operations, which can effectively protect the patients upper tract functions.

  1. Redox equilibrium in mucosal T cells tunes the intestinal TCR signaling threshold.

    PubMed

    Reyes, Brenda M Rivera; Danese, Silvio; Sans, Miquel; Fiocchi, Claudio; Levine, Alan D

    2005-08-15

    Mucosal immune tolerance in the healthy intestine is typified by lamina propria T cell (LPT) functional hyporesponsiveness after TCR engagement when compared with peripheral blood T cell (PBT). When LPT from an inflamed intestine are activated through TCR cross-linking, their responsiveness is stronger. LPT are thus capable of switching from a tolerant to a reactive state, toggling between high and low thresholds of activation. We demonstrate that in normal LPT global tyrosine phosphorylation upon TCR cross-linking or an increase in intracellular H2O2, an inhibitor of protein tyrosine phosphatases, is muted. Thus, we propose that LPT have a greater reducing capacity than PBT, shifting the balance between kinases and protein tyrosine phosphatases in favor of the latter. Surface gamma-glutamyl transpeptidase, an indirect indicator of redox potential, and glutathione are significantly elevated in LPT compared with PBT, suggesting that elevated glutathione detoxifies TCR-induced reactive oxygen species. When glutathione is depleted, TCR-induced LPT tyrosine phosphorylation rises to PBT levels. Conversely, increasing glutathione in PBT attenuates tyrosine phosphorylation. In LPT isolated from inflamed mucosa, TCR cross-linking induces greater phosphorylation, and gamma-glutamyl transpeptidase levels are reduced compared with those from autologous noninflamed tissue. We conclude that the high TCR signaling threshold of mucosal T cells is tuned by intracellular redox equilibrium, whose dysregulation may mediate intestinal inflammation. PMID:16081782

  2. Mycoplasma pneumonia-associated mucositis

    PubMed Central

    Varghese, Cyril; Sharain, Korosh; Skalski, Joseph; Ramar, Kannan

    2014-01-01

    We present a case of a young man with severe mucositis following an upper respiratory tract infection limited to the ophthalmic and oral mucosa while sparing the rest of the skin, genitalia and perianal regions. Investigations revealed that the mucositis was a rare extrapulmonary manifestation of Mycoplasma pneumoniae infection. He had progressive vision-threatening symptoms despite antibiotics and best supportive care and thus was treated with intravenous corticosteroids, immunoglobulins, temporary ocular amniotic membrane grafts and tarsorrhaphy. The patient made an almost complete recovery over 6 weeks. PMID:24626386

  3. Characterization of thyroidal glutathione reductase

    SciTech Connect

    Raasch, R.J.

    1989-01-01

    Glutathione levels were determined in bovine and rat thyroid tissue by enzymatic conjugation with 1-chloro-2,4-dinitrobenzene using glutathione S-transferase. Bovine thyroid tissue contained 1.31 {+-} 0.04 mM reduced glutathione (GSH) and 0.14 {+-} 0.02 mM oxidized glutathione (GSSG). In the rat, the concentration of GSH was 2.50 {+-} 0.05 mM while GSSG was 0.21 {+-} 0.03 mM. Glutathione reductase (GR) was purified from bovine thyroid to electrophoretic homogeneity by ion exchange, affinity and molecular exclusion chromatography. A molecular weight range of 102-109 kDa and subunit size of 55 kDa were determined for GR. Thyroidal GR was shown to be a favoprotein with one FAD per subunit. The Michaelis constants of bovine thyroidal GR were determined to be 21.8 {mu}M for NADPH and 58.8 {mu}M for GSSG. The effect of thyroid stimulating hormone (TSH) and thyroxine (T{sub 4}) on in vivo levels of GR and glucose 6-phosphate dehydrogenase were determined in rat thyroid homogenates. Both enzymes were stimulated by TSH treatment and markedly reduced following T{sub 4} treatment. Lysosomal hydrolysis of ({sup 125}I)-labeled and unlabeled thyroglobulin was examined using size exclusion HPLC.

  4. Recent advances in mucosal vaccines and adjuvants.

    PubMed

    Eriksson, Kristina; Holmgren, Jan

    2002-10-01

    Mucosal vaccines may be used both to prevent mucosal infections through the activation of antimicrobial immunity and to treat systemic inflammatory diseases through the induction of antigen-specific mucosal tolerance. New, efficient mucosal adjuvants for human use have been designed based on, amongst others, bacterial toxins and their derivatives, CpG-containing DNA, and different cytokines and chemokines, with the aim of improving the induction of mucosal Th1 and Th2 responses. Mucosal delivery systems, in particular virus-like particles, have been shown to enhance the binding, uptake and half-life of the antigens, as well as target the vaccine to mucosal surfaces. DNA vaccines are currently being developed for administration at mucosal surfaces. However, there have also been failures, such as the withdrawal of an oral vaccine against rotavirus diarrhea and a nasal vaccine against influenza, because of their potential side effects. PMID:12183170

  5. 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

  6. Localized ileal giant pseudopolyposis in Crohn's disease: a case report.

    PubMed

    Limaiem, F; Ben Slama, S; Jedidi, S; Aloui, S; Lahmar, A; Bouraoui, S; Mzabi, S

    2012-08-01

    Localized giant pseudopolyposis is a rare complication in inflammatory bowel disease defined as a pseudopolyp (isolated or clustered) larger than 1.5 cm in size. Giant pseudopolyps are more commonly found in ulcerative colitis compared to Crohn's disease and mainly involve the left colon. A 26-year-old male patient with a two-year history of Crohn's disease was admitted with increasing abdominal pain, vomiting, anorexia, weight loss and fever. On physical examination, the abdomen was diffusely tender. Computed tomography showed diffuse irregular thickening of the ileal wall and stenosis of the terminal ileum. The patient underwent ileo-cecal resection with re-anastomosis. The ileal portion of the resected specimen harboured multiple finger-like pedunculated polyps, with the smallest measuring 0.5 cm and the largest measuring 1.8 cm. Histologically, the polyps were consistent with granulation tissue. No evidence of dysplasia or malignancy was found. The post-operative course was uneventful considering one month follow-up. This report illustrates an unusual case of giant pseudopolyposis involving the ileum in a patient with Crohn's disease. The natural history of these lesions, as well as their optimal management, remain uncertain. PMID:23316625

  7. Nanotechnology solutions for mucosal immunization.

    PubMed

    Chadwick, Sandra; Kriegel, Christina; Amiji, Mansoor

    2010-03-18

    The current prevalence of infectious diseases in many developing regions of the world is a serious burden, impacting both the general health as well as economic growth of these communities. Additionally, treatment with conventional medication becomes increasingly challenging due to emergence of new and drug resistant strains jeopardizing the progress made in recent years towards control and elimination of certain types of infectious diseases. Thus, from a public health perspective, prevention such as through immunization by vaccination, which has proven to be most effective, might be the best alternative to prevent and combat infectious diseases in these regions. To achieve this, development of wide-scale immunization programs become necessary including vaccines that can easily and widely be distributed, stored and administered. Mucosal vaccines offer great potential since they can be administered via oral or intranasal delivery route which does not require trained personnel, avoids the use of needles and improves overall patient compliance and acceptance. However, it necessitates the implementation of specific immunization strategies to improve their efficacy. Application of nanotechnology to design and create particle mediated delivery systems that can efficiently encapsulate vaccine components for protection of the sensitive payload, target the mucosal immune system and incorporate mucosal adjuvants maximizing immune response is key strategy to improve the effectiveness of mucosal vaccines. PMID:19931581

  8. Immunology of Gut Mucosal Vaccines

    PubMed Central

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

    2011-01-01

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

  9. 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

  10. Mucosal Immunity and the Microbiome

    PubMed Central

    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

  11. Prospects for human mucosal vaccines.

    PubMed

    Mestecky, J; McGhee, J R

    1992-01-01

    The selective induction of antibodies in external secretions and mucosal T cell-mediated immunity are desirable for the prevention of various systemic as well as predominantly mucosa-restricted infections. An enormous surface area of mucosal membranes is protected primarily by antibodies that belong, in many species, to the IgA isotype. Such antibodies are produced locally by large numbers of IgA-containing plasma cells distributed in subepithelial spaces of mucosal membranes and in the stroma of secretory glands. In humans and in some animal species, plasma-derived IgA antibodies do not enter external secretions in significant quantities and systemically administered preformed IgA antibodies would be of little use for passive immunization. Systemic administration of microbial antigens may boost an effective S-IgA immune response only in a situation whereby an immunized individual had previously encountered the same antigen by the mucosal route. Immunization routes that involve ingestion or possibly inhalation of antigens lead to the induction of not only local but also generalized immune responses, manifested by the parallel appearance of S-IgA antibodies to ingested or inhaled antigens in secretions of glands distant from the site of immunization. Convincing evidence is available that antigen-sensitized and IgA-committed precursors of plasma cells and T cells from IgA inductive sites (e.g., BALT, GALT, and tonsils) are disseminated to the gut, other mucosa-associated tissues, and exocrine glands. However, due to the limited absorption of desired antigens from the gut lumen of orally immunized individuals, repeated large doses of antigens are required for an effective S-IgA response. Novel antigen delivery systems for the stimulation of such responses has been briefly reviewed here. These, of course, include genetically engineered bacteria and viruses, CT/CFB, liposomes and microspheres. Live attenuated or genetically manipulated bacteria expressing other microbial antigens have been used for selective colonization of GALT. Unique antigen packaging and the use of adjuvants suitable for oral administration hold promise for an efficient antigen delivery to critical tissues in the intestine and deserve extensive exploration. The oral immunization route appears to have many advantages over systemic immunization; however, one must consider alternate IgA inductive sites and compartmentalization within the Common Mucosal Immune System. In addition to providing immunity on mucosal surfaces, which are the most common sites of entry of infectious agents, the mucosal routes of administration are more acceptable and do not require stringent criteria applicable for injectable vaccines, storage problems may be simplified, and large populations of individuals can be immunized simultaneously without the assistance of highly trained health personnel. PMID:1295333

  12. 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

  13. Ca/sup + +/- and cyclic AMP-induced changes in intact cell phosphorylation of ileal microvillus membrane proteins

    SciTech Connect

    Sharp, G.W.G.; Hannah, C.M.; Cohen, M.; Donowitz, M.

    1986-03-05

    Pieces of rabbit distal ileal mucosa, with the muscularis propria and serosa removed, were incubated for 90 minutes in Krebs-Ringer bicarborate buffer (KRB) with /sup 32/PO/sub 4/ to label the intracellular nucleotide pools. After rinsing, the mucosal pieces were transferred to KRB in the absence and presence of 10 ..mu..M A23187 or 10 mM theophylline. After a further 10 minutes the cells were scraped off and microvillus membranes prepared. The membranes were solubilized, subjected to two dimensional gel electrophoresis and autoradiography, and analyzed by densitometry. A23187 increased the phosphorylation of four microvillus membrane proteins with M/sub r/ of 32, 52, 110 and 116K. Increased phosphorylation of the 52 and 116K proteins has also been detected in microvillus membranes subjected to Ca/sup + +/ and calmodulin in the presence of ..gamma..-/sup 32/P-ATP. Theophylline increased the phosphorylation of the same 32 and 52K proteins and, additionally, of a second 32K peptide. While any of these proteins could be involved in the control of electrolyte transport, it is noteworthy that increased Ca/sup + +/, and increased cyclic AMP levels exert similar effects upon intestinal electrolyte transport. That A23187 and theophylline both increase the phosphorylation of the 32 and 52K proteins increases the possibility that these are involved in ion transport.

  14. Effects of Prostaglandins and Cholera Enterotoxin on Intestinal Mucosal Cyclic AMP Accumulation

    PubMed Central

    Kimberg, Daniel V.; Field, Michael; Gershon, Elaine; Henderson, Antonia

    1974-01-01

    Both cholera enterotoxin and certain prostaglandins have been shown to stimulate intestinal fluid secretion in vivo, to cause ion flux changes in vitro similar to those caused by addition of cyclic 3′,5′-adenosine monophosphate (cyclic AMP), and to activate intestinal mucosal adenyl cyclase. It has been suggested that the effects of the enterotoxin on intestinal cyclic AMP metabolism may be indirect, and that locally synthesized prostaglandins may serve as required intermediates for the effects of the enterotoxin in activating intestinal mucosal adenyl cyclase. In order to clarify certain aspects of the mechanisms by which these two agents alter intestinal mucosal cyclic AMP metabolism and ion transport, their effects on cyclic AMP accumulation in rabbit ileal mucosa were examined in vitro. Addition of 5 μg per ml (75 μg per 150 mg mucosa) of purified cholera enterotoxin produced a peak increase in cyclic AMP level in 3 h but there was a time delay of at least 30 min before any effect was observed. Inhibition of cyclic nucleotide phosphodiesterase with theophylline failed to reduce this time delay. In contrast, addition of prostaglandin E1 (PGE1) increased the cyclic AMP level rapidly, a peak effect being observed in 2 min. The time of the peak prostaglandin-induced changes in cyclic AMP level and short-circuit current correlated closely. A maximal increment in cyclic AMP level was achieved with 5 × 10−5 M PGE1. When 10−4 M PGE1 was added to mucosa already maximally stimulated with cholera toxin, the resulting cyclic AMP level was equal to the sum of the levels reached when each agent was added alone. Furthermore, the effects of the enterotoxin on mucosal cyclic AMP levels were not influenced by indomethacin under conditions where mucosal prostaglandins synthesis was inhibited. The results suggest that endogenous prostaglandins do not provide an essential link in the activation of intestinal mucosal adenyl cyclase by cholera enterotoxin. The present study also indicates that the effect of cholera enterotoxin on intestinal mucosal cyclic AMP metabolism involves a definite time delay which is not due to cyclic nucleotide phosphodiesterase activity. PMID:4359941

  15. The effect of a commercial enzyme preparation on apparent metabolizable energy, the true ileal amino acid digestibility, and endogenous ileal lysine losses in broiler chickens.

    PubMed

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

    2007-04-01

    The effect of a commercial enzyme preparation containing xylanase, alpha-amylase, and beta-glucanase on dietary AME content and the apparent and true ileal amino acid digestibility of a corn-soy broiler diet and endogenous ileal lysine flow was determined. Two predominantly corn-soy diets also containing wheat bran and canola meal were formulated; one diet contained no added enzymes, whereas the other was supplemented with alpha-amylase, beta-glucanase, and xylanase. Titanium dioxide was included as an indigestible marker. The diets were given to broiler chickens, and AME and true ileal amino acid digestibility were determined. Portions of the 2 test diets were guanidinated and fed to similar aged broiler chickens and endogenous lysine flows determined. The chickens appeared healthy throughout the study, and the mean bird weights at the time of slaughter were not significantly different (P < 0.05) among any of the treatment groups. Dietary AME content was significantly (P < 0.05) higher for the enzyme-supplemented corn-soy diet (2,829 kcal/kg) compared with its unsupplemented control diet (2,766 kcal/kg). True ileal amino acid digestibility was significantly (P < 0.05) higher for all amino acids investigated. The increase ranged from 4% for arginine and glutamic acid to 12% for cystine. There was no significant difference in endogenous ileal lysine flow between broilers fed the unsupplemented diet and those fed the enzyme-supplemented diet. Overall, enzyme supplementation with an enzyme blend containing alpha-amylase, beta-glucanase, and xylanase increased the AME content of a corn-soy broiler diet as well as apparent and true ileal amino acid digestibility for all amino acids, but had no effect on endogenous ileal lysine flow. PMID:17369537

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

    PubMed

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

    2015-01-01

    5-Fluorouracil (5-FU)-induced intestinal mucositis is one of the most common morbidities in chemotherapy and involves the reactive oxygen species (ROS) system, apoptosis, and inflammatory cytokines. Rebamipide exerts a mucosal-protective effect, mediated through several mechanisms. The aim of this study was to evaluate the effects of rebamipide in 5-FU-induced mouse small-intestinal mucositis. BALB/c mice were assigned randomly to four groups; (1) control group (n=10; receiving saline orally for 6 d), (2) rebamipide group (n=10; 150 mg/kg rebamipide for 6 d orally), (3) 5-FU group (n=10; 30 mg/kg 5-FU for 5 d, intraperitoneally (i.p.)), and (4) rebamipide +5-FU group (n=10; 150 mg/kg rebamipide for 6 d orally and 30 mg/kg 5-FU for 5 d, i.p.). Body weights and diarrhea scales were assessed. At day 5, the mice were sacrificed. Small intestinal tissue was used for: (1) hematoxylin and eosin (HE) staining for determination of small intestinal villi height, (2) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, (3) immunohistochemistry for inducible nitric oxide synthase (iNOS), F4/80, and transforming growth factor (TGF)-?1, (4) measurement of serum and tissue GSH levels, and (5) measurement of serum tumor necrosis factor (TNF)-? levels. Rebamipide attenuated the severity of mucosal injury reflected by body weight changes, degrees of diarrhea, and heights of villi. Rebamipide reduced the expression of iNOS and TGF-?1, apoptosis, macrophage accumulation, serum TNF-? levels, and prevented reductions in serum and tissue glutathione (GSH) levels by 5-FU administration. These results suggest that rebamipide promotes several mechanisms of mucosal protection and attenuated the 5-FU-induced mucosal injury. In conclusion, administration of rebamipide may have significant protective effects against 5-FU-induced intestinal mucositis. PMID:25747976

  17. Utility of Neutrophil Fcγ Receptor I (CD64) Index as a Biomarker for Mucosal Inflammation in Pediatric Crohn's Disease

    PubMed Central

    Minar, Phillip; Haberman, Yael; Jurickova, Ingrid; Wen, Ting; Rothenberg, Marc E.; Kim, Mi-Ok; Saeed, Shehzad A.; Baldassano, Robert N.; Stephens, Michael; Markowitz, James; Rosh, Joel; Crandall, Wallace V.; Heyman, Melvin B.; Mack, David R.; Griffiths, Anne M.; Baker, Susan S.; Hyams, Jeffrey S.; Kugathasan, Subra; Denson, Lee A.

    2014-01-01

    Background Neutrophil expression of the Fcγ receptor I (CD64) is upregulated in adult patients with clinically active inflammatory bowel disease (IBD). We tested the relationship of CD64 with mucosal inflammation and clinical relapse in pediatric Crohn's disease (CD). Methods In a cohort of 208 newly diagnosed CD and 43 non-IBD controls, ileal expression of FcγRI/S100A9 was determined by RNA sequencing from biopsies obtained at ileocolonoscopy. In a second cohort, we tested for the peripheral blood polymorphonuclear neutrophil (PMN) CD64 index from 26 newly diagnosed CD, 30 non-IBD controls and 83 children with established CD. Results Ileal FcγRIA mRNA expression was significantly elevated in CD at diagnosis compared with non-IBD controls (p<0.001), and correlated with ileal S100A9 (calprotectin) expression (r=0.83, p<0.001). The median(range) PMN CD64 index for newly diagnosed CD was 2.3(0.74-9.3) compared with 0.76(0.39-1.2) for non-IBD controls (p<0.001) with 96% sensitivity and 90% specificity at the cut point of 1.0. The PMN CD64 index significantly correlated with mucosal injury as measured by the Simple Endoscopic Score-CD (SES-CD, r=0.62, p<0.001). CD patients in clinical remission receiving maintenance therapy with a PMN CD64 index <1.0 had a sustained remission rate of 95% over the following 12 months compared with 56% in those with a PMN CD64 index >1.0 (p<0.01). Conclusions An elevated PMN CD64 index is associated with both mucosal inflammation and an increased risk for clinical relapse in pediatric CD. The PMN CD64 index is a reliable marker for sustained remission in CD patients receiving maintenance therapy. PMID:24788216

  18. Primary mucosal melanomas: a comprehensive review

    PubMed Central

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

    2012-01-01

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

  19. The Mucosal Immune System of Teleost Fish

    PubMed Central

    Salinas, Irene

    2015-01-01

    Teleost fish possess an adaptive immune system associated with each of their mucosal body surfaces. Evidence obtained from mucosal vaccination and mucosal infection studies reveal that adaptive immune responses take place at the different mucosal surfaces of teleost. The main mucosa-associated lymphoid tissues (MALT) of teleosts are the gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), the gill-associated lymphoid tissue (GIALT) and the recently discovered nasopharynx-associated lymphoid tissue (NALT). Teleost MALT includes diffuse B cells and T cells with specific phenotypes different from their systemic counterparts that have co-evolved to defend the microbe-rich mucosal environment. Both B and T cells respond to mucosal infection or vaccination. Specific antibody responses can be measured in the gills, gut and skin mucosal secretions of teleost fish following mucosal infection or vaccination. Rainbow trout studies have shown that IgT antibodies and IgT+ B cells are the predominant B cell subset in all MALT and respond in a compartmentalized manner to mucosal infection. Our current knowledge on adaptive immunity in teleosts is limited compared to the mammalian literature. New research tools and in vivo models are currently being developed in order to help reveal the great intricacy of teleost mucosal adaptive immunity and help improve mucosal vaccination protocols for use in aquaculture. PMID:26274978

  20. Genetics Home Reference: Glutathione synthetase deficiency

    MedlinePLUS

    ... which takes place in most of the body's cells. This cycle is necessary for producing a molecule called glutathione. Glutathione protects cells from damage caused by unstable oxygen-containing molecules, ...

  1. 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

  2. Body composition in ileostomy patients with and without ileal resection.

    PubMed Central

    Cooper, J C; Laughland, A; Gunning, E J; Burkinshaw, L; Williams, N S

    1986-01-01

    Body composition was measured in 24 patients who had previously undergone proctocolectomy and ileostomy. One group (control group) had undergone resection of only small amounts of terminal ileum (median 4 cm), the other group of patients (resected group) had undergone resection of greater lengths of small bowel (median 54 cm). These values of body composition were then compared with predicted values in normal subjects. Proctocolectomy and ileostomy without ileal resection did not significantly affect body weight, or the body contents of fat or water, but led to a reduction in total body nitrogen and total body potassium, suggesting a reduction in fat free mass. A modest resection of the terminal ileum undertaken during the course of proctocolectomy decreased body weight largely because of a reduction in body fat. None of the ileostomy patients was found to be dehydrated. PMID:3721291

  3. Glutathione production by recombinant Escherichia coli expressing bifunctional glutathione synthetase.

    PubMed

    Wang, Dezheng; Wang, Cheng; Wu, Hui; Li, Zhimin; Ye, Qin

    2016-01-01

    Glutathione (GSH) is an important bioactive substance applied widely in pharmaceutical and food industries. Due to the strong product inhibition in the GSH biosynthetic pathway, high levels of intracellular content, yield and productivity of GSH are difficult to achieve. Recently, a novel bifunctional GSH synthetase was identified to be less sensitive to GSH. A recombinant Escherichia coli strain expressing gshF encoding the bifunctional glutathione synthetase of Streptococcus thermophilus was constructed for GSH production. In this study, efficient GSH production using this engineered strain was investigated. The cultivation process was optimized by controlling dissolved oxygen (DO), amino acid addition and glucose feeding. 36.8mM (11.3g/L) GSH were formed at a productivity of 2.06mM/h when the amino acid precursors (75mM each) were added and glucose was supplied as the sole carbon and energy source. PMID:26586402

  4. 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

  5. Seasonal Variation of Glutathione and Glutathione Reductase in Needles of Picea abies 1

    PubMed Central

    Esterbauer, Hermann; Grill, Dieter

    1978-01-01

    In spruce (Picea abies) needles glutathione and glutathione reductase show a periodic seasonal variation with significantly increased levels during the winter. It is proposed that glutathione and glutathione reductase play an important role for the winter hardiness of leaves from evergreen plants. PMID:16660223

  6. Echinacea purpurea and mucosal immunity.

    PubMed

    Hall, H; Fahlman, M M; Engels, H J

    2007-09-01

    This investigation examined the effects of Echinacea purpurea on mucosal immunity and the incidence and duration of upper respiratory tract infection (URTI). 32 subjects completed an exercise protocol known to affect mucosal immunity. Saliva was collected prior to and five minutes after completion of exercise testing. Subjects then took either a placebo (C) or Echinacea supplement (E) for 4 weeks and the testing procedure was repeated. Each time, s-IgA concentrations and saliva flow rate were measured and the secretion rate of s-IgA was calculated. In addition, standard logs indicating symptoms of URTI were completed throughout the study. Both groups demonstrated significant exercise induced reductions in s-IgA (C - 69 %; E - 43 %) and the secretion rate of s-IgA (C - 79 %; E - 53 %) at the beginning of the study (p < 0.05). Following the 4-week intervention, only the control group experienced the post intervention decrease in s-IgA (C - 45 %; E + 7 %) and the secretion rate of s-IgA (C - 45 %; E - 7 %). Further, while there was no significant difference in the number of URTI between groups, the reported duration was significantly different (C 8.6 days vs. E 3.4 days). The results suggest that Echinacea may attenuate the mucosal immune suppression known to occur with intense exercise and reduce the duration of URTI that subjects incur. PMID:17436202

  7. 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

  8. Bacterial toxins as mucosal adjuvants.

    PubMed

    Freytag, L C; Clements, J D

    1999-01-01

    The use of mucosally administered killed bacteria or viruses as vaccines has a number of attractive features over the use of viable attenuated organisms, including safety, cost, storage and ease of delivery. Unfortunately, mucosally administered killed organisms are not usually effective as vaccines. The use of LT(R192G), a genetically detoxified derivative of LT, as a mucosal adjuvant enables the use of killed bacteria or viruses as vaccines by enhancing the overall humoral and cellular host immune response to these organisms, especially the Th1 arm of the immune response. With this adjuvant, protective responses equivalent to those elicited by live attenuated organisms can be achieved with killed organisms without the potential side effects. These findings have significant implications for vaccine development and further support the potential of LT(R192G) to function as a safe, effective adjuvant for mucosally administered vaccines. There are a number of unresolved issues regarding the use of LT and CT mutants as mucosal adjuvants. Both active-site and protease-site mutants of LT and CT have been constructed and adjuvanticity reported for these molecules in various animal models and with different antigens. There needs to be a side-by-side comparison of CT, LT, active-site mutants, protease-site mutants and recombinant B subunits regarding the ability to induce specific, targeted immunological outcomes as a function of route of immunization and nature of the co-administered antigen. Those side-by-side comparisons have not been carried out and there is a substantial body of evidence indicating that the outcomes may very well be different. With that information, vaccine strategies could be designed employing the optimum adjuvant/antigen formulation and route of administration for a variety of bacterial and viral pathogens. Also lacking is an understanding of the underlying cellular and intracellular signaling pathways activated by these different molecules and an understanding of the mechanisms of adjuvanticity at the cellular level. These are important issues because they take us beyond the phenomenological observations of "enhanced immunity" to a more clear understanding of the mechanisms of adjuvant activity. PMID:9893362

  9. Mucosal Immune System and M Cell-targeting Strategies for Oral Mucosal Vaccination

    PubMed Central

    Kim, Sae-Hae; Lee, Kyung-Yeol

    2012-01-01

    Vaccination is one of the most effective methods available to prevent infectious diseases. Mucosa, which are exposed to heavy loads of commensal and pathogenic microorganisms, are one of the first areas where infections are established, and therefore have frontline status in immunity, making mucosa ideal sites for vaccine application. Moreover, vaccination through the mucosal immune system could induce effective systemic immune responses together with mucosal immunity in contrast to parenteral vaccination, which is a poor inducer of effective immunity at mucosal surfaces. Among mucosal vaccines, oral mucosal vaccines have the advantages of ease and low cost of vaccine administration. The oral mucosal immune system, however, is generally recognized as poorly immunogenic due to the frequent induction of tolerance against orally-introduced antigens. Consequently, a prerequisite for successful mucosal vaccination is that the orally introduced antigen should be transported across the mucosal surface into the mucosa-associated lymphoid tissue (MALT). In particular, M cells are responsible for antigen uptake into MALT, and the rapid and effective transcytotic activity of M cells makes them an attractive target for mucosal vaccine delivery, although simple transport of the antigen into M cells does not guarantee the induction of specific immune responses. Consequently, development of mucosal vaccine adjuvants based on an understanding of the biology of M cells has attracted much research interest. Here, we review the characteristics of the oral mucosal immune system and delineate strategies to design effective oral mucosal vaccines with an emphasis on mucosal vaccine adjuvants. PMID:23213309

  10. [Reduced glutathione and anaerobic threshold].

    PubMed

    Pigozzi, F; Parisi, A; Di Luigi, L; Menchinelli, C; Marciano, R; Volta, B; Battista, S

    1996-01-01

    In this study the authors evaluate the relationship existing between reduced glutathione (GSH) and increased indexes of muscle performance. GSH has a protective action on the cell either against the oxidative stress or for its ability of removing through out the body xenobiotic substances circulating. 15 male competitive pentathlon athletes were the sample of this research. The aim of the research is to evaluate the possible role of GSH to determine the anaerobic threshold through its blotting function. PMID:8767952

  11. 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

  12. 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

  13. Glutathione, altruistic metabolite in fungi.

    PubMed

    Pcsi, Istvn; Prade, Rolf A; Penninckx, Michel J

    2004-01-01

    Glutathione (GSH; gamma-L-glutamyl-L-cysteinyl-glycine), a non-protein thiol with a very low redox potential (E'0 = 240 mV for thiol-disulfide exchange), is present in high concentration up to 10 mM in yeasts and filamentous fungi. GSH is concerned with basic cellular functions as well as the maintenance of mitochondrial structure, membrane integrity, and in cell differentiation and development. GSH plays key roles in the response to several stress situations in fungi. For example, GSH is an important antioxidant molecule, which reacts non-enzymatically with a series of reactive oxygen species. In addition, the response to oxidative stress also involves GSH biosynthesis enzymes, NADPH-dependent GSH-regenerating reductase, glutathione S-transferase along with peroxide-eliminating glutathione peroxidase and glutaredoxins. Some components of the GSH-dependent antioxidative defence system confer resistance against heat shock and osmotic stress. Formation of protein-SSG mixed disulfides results in protection against desiccation-induced oxidative injuries in lichens. Intracellular GSH and GSH-derived phytochelatins hinder the progression of heavy metal-initiated cell injuries by chelating and sequestering the metal ions themselves and/or by eliminating reactive oxygen species. In fungi, GSH is mobilized to ensure cellular maintenance under sulfur or nitrogen starvation. Moreover, adaptation to carbon deprivation stress results in an increased tolerance to oxidative stress, which involves the induction of GSH-dependent elements of the antioxidant defence system. GSH-dependent detoxification processes concern the elimination of toxic endogenous metabolites, such as excess formaldehyde produced during the growth of the methylotrophic yeasts, by formaldehyde dehydrogenase and methylglyoxal, a by-product of glycolysis, by the glyoxalase pathway. Detoxification of xenobiotics, such as halogenated aromatic and alkylating agents, relies on glutathione S-transferases. In yeast, these enzymes may participate in the elimination of toxic intermediates that accumulate in stationary phase and/or act in a similar fashion as heat shock proteins. GSH S-conjugates may also form in a glutathione S-transferases-independent way, e.g. through chemical reaction between GSH and the antifugal agent Thiram. GSH-dependent detoxification of penicillin side-chain precursors was shown in Penicillium sp. GSH controls aging and autolysis in several fungal species, and possesses an anti-apoptotic feature. PMID:15518828

  14. Voice Disorders in Mucosal Leishmaniasis

    PubMed Central

    Ruas, Ana Cristina Nunes; Lucena, Mrcia Mendona; da Costa, Ananda Dutra; Vieira, Jssica Rafael; de Arajo-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

  15. Oxygen metabolite-induced cytotoxicity to cultured rat gastric mucosal cells

    SciTech Connect

    Hiraishi, H.; Terano, A.; Ota, S.; Ivey, K.J.; Sugimoto, T.

    1987-07-01

    Reactive oxygen metabolites have been reported to be responsible for the pathogenesis of ischemia-induced gastric mucosal lesion. The authors have investigated the possible protective effect of specific enzymes and oxygen radical scavenging agents on oxygen metabolite-induced injury to cultured gastric mucosal cells. Oxygen-reactive metabolites were generated by 1 mM xanthine and 10-100 mU/ml xanthine oxidase. Cytotoxicity was quantified by measuring /sup 51/Cr release from prelabeled cells. Xanthine oxidase caused a dose-dependent increase of /sup 51/Cr release in the presence of 1 mM xanthine. Catalase diminished xanthine-xanthine oxidase-induced /sup 51/Cr release in a dose-dependent manner. Superoxide dismutase failed to affect the amounts of /sup 51/Cr release induced by xanthine plus xanthine oxidase. Pretreatment with diethyl maleate potentiated oxygen radical-mediated /sup 51/Cr release dose dependently. The presence of ferrous ion or ethylenediaminetetraacetic acid-chelated iron did not alter xanthine-xanthine oxidase-induced cellular injury. They conclude that in vitro (1) oxygen metabolites, extracellularly generated, have a direct toxic effect on gastric mucosal cells; (2) hydrogen peroxide is a major mediator of oxygen metabolite-induced gastric cell injury; (3) the oxygen-derived superoxide and hydroxyl radicals are less toxic to gastric mucosal cells than hydrogen peroxide; and (4) intracellular glutathione, which detoxifies hydrogen peroxide, may be involved in antioxidant defense mechanisms.

  16. Mucosal immunity and probiotics in fish.

    PubMed

    Lazado, Carlo C; Caipang, Christopher Marlowe A

    2014-07-01

    Teleost mucosal immunity has become the subject of unprecedented research studies in recent years because of its diversity and defining characteristics. Its immune repertoire is governed by the mucosa-associated lymphoid tissues (MALT) which are divided into gut-associated lymphoid tissues (GALT), skin-associated lymphoid tissues (SALT), and gill-associated lymphoid tissues (GIALT). The direct contact with its immediate environment makes the mucosal surfaces of fish susceptible to a wide variety of pathogens. The inherent immunocompetent cells and factors in the mucosal surfaces together with the commensal microbiota have pivotal role against pathogens. Immunomodulation is a popular prophylactic strategy in teleost and probiotics possess this beneficial feature. Most of the studies on the immunomodulatory properties of probiotics in fish mainly discussed their impacts on systemic immunity. In contrast, few of these studies discussed the immunomodulatory features of probiotics in mucosal surfaces and are concentrated on the influences in the gut. Significant attention should be devoted in understanding the relationship of mucosal immunity and probiotics as the present knowledge is limited and are mostly based on extrapolations of studies in humans and terrestrial vertebrates. In the course of the advancement of mucosal immunity and probiotics, new perspectives in probiotics research, e.g., probiogenomics have emerged. This review affirms the relevance of probiotics in the mucosal immunity of fish by revisiting and bridging the current knowledge on teleost mucosal immunity, mucosal microbiota and immunomodulation of mucosal surfaces by probiotics. Expanding the knowledge of immunomodulatory properties of probiotics especially on mucosal immunity is essential in advancing the use of probiotics as a sustainable and viable strategy for successful fish husbandry. PMID:24795079

  17. Intestinal mucosal changes and upregulated calcium transporter and FGF-23 expression during lactation: Contribution of lactogenic hormone prolactin.

    PubMed

    Wongdee, Kannikar; Teerapornpuntakit, Jarinthorn; Sripong, Chanakarn; Longkunan, Asma; Chankamngoen, Wasutorn; Keadsai, Chutiya; Kraidith, Kamonshanok; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2016-01-15

    As the principal lactogenic hormone, prolactin (PRL) not only induces lactogenesis but also enhances intestinal calcium absorption to supply calcium for milk production. How the intestinal epithelium res-ponses to PRL is poorly understood, but it is hypothesized to increase mucosal absorptive surface area and calcium transporter expression. Herein, lactating rats were found to have greater duodenal, jejunal and ileal villous heights as well as cecal crypt depths than age-matched nulliparous rats. Morphometric analyses in the duodenum and cecum showed that their mucosal adaptations were diminished by bromocriptine, an inhibitor of pituitary PRL release. PRL also upregulated calcium transporter expression (e.g., TRPV6 and PMCA1b) in the duodenum of lactating rats. Since excessive calcium absorption could be detrimental to lactating rats, local negative regulator of calcium absorption, e.g., fibroblast growth factor (FGF)-23, should be increased. Immunohistochemistry confirmed the upregulation of FGF-23 protein expression in the duodenal and cecal mucosae of lactating rats, consistent with the enhanced FGF-23 mRNA expression in Caco-2 cells. Bromocriptine abolished this lactation-induced FGF-23 expression. Additionally, FGF-23 could negate PRL-stimulated calcium transport across Caco-2 monolayer. In conclusion, PRL was responsible for the lactation-induced mucosal adaptations, which were associated with compensatory increase in FGF-23 expression probably to prevent calcium hyperabsorption. PMID:26657069

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

    PubMed Central

    Belmonte, Liliana; Coffier, Mose; Pessot, Florence Le; Miralles-Barrachina, Olga; Hiron, Martine; Leplingard, Antony; Lemeland, Jean-Franois; Hecketsweiler, Bernadette; Daveau, Maryvonne; Ducrott, Philippe; Dchelotte, Pierre

    2007-01-01

    AIM: To evaluate the effect of glutamine on intestinal mucosa integrity, glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. METHODS: Plasma acute phase proteins (APP), jejunal APP mRNA levels, liver and jejunal glutathione concentrations were measured before and one, three and seven days after turpentine injection in 4 groups of control, protein-restricted, protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed. RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height, and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil, glutamine supplementation restored villus heights and glutathione concentration (3.24 1.05 vs 1.72 0.46 ?mol/g tissue, P < 0.05) in the jejunum, whereas in the liver glutathione remained low. Glutamine markedly increased jejunal ?1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model. PMID:17569119

  19. 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

  20. Ileal lesions in patients with ulcerative colitis after ileo-rectal anastomosis: Relationship with colonic metaplasia

    PubMed Central

    Biancone, Livia; Calabrese, Emma; Palmieri, Giampiero; Petruzziello, Carmelina; Onali, Sara; Sica, Giuseppe Sigismondo; Cossignani, Marta; Condino, Giovanna; Das, Kiron Moy; Pallone, Francesco

    2008-01-01

    AIM: To assess whether in ulcerative colitis (UC) patients with ileo-rectal anastomosis (IRA), ileal lesions may develop in the neo-terminal-ileum and their possible relation with phenotypic changes towards colonic epithelium. METHODS: A total of 19 patients with IRA under regular follow up were enrolled, including 11 UC and 8 controls (6 Crohns disease, CD; 1 familial adenomatous polyposis, FAP; 1 colon cancer, colon K). Ileal lesions were identified by ileoscopy with biopsies taken from the ileum (involved and uninvolved) and from the rectal stump. Staining included HE and immunohistochemistry using monoclonal antibodies against colonic epithelial protein CEP (Das-1) and human tropomyosin isoform 5, hTM5 (CG3). Possible relation between development of colonic metaplasia and ileal lesions was investigated. RESULTS: Stenosing adenocarcinoma of the rectal stump was detected in 1 UC patient. The neo-terminal ileum was therefore investigated in 10/11 UC patients. Ileal ulcers were detected in 7/10 UC, associated with colonic metaplasia in 4/7 (57.1%) and Das-1 and CG3 reactivity in 3/4 UC. In controls, recurrence occurred in 4/6 CD, associated with colonic metaplasia in 3/4 and reactivity with Das-1 and CG3 in 2/3. CONCLUSION: Present findings suggest that in UC, ileal lesions associated with changes towards colonic epithelium may develop also after IRA. Changes of the ileal content after colectomy may contribute to the development of colonic metaplasia, leading to ileal lesions both in the pouch and in the neo-terminal ileum after IRA. PMID:18785281

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

    PubMed

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

    2015-07-01

    An experiment was conducted to estimate true ileal phosphorus (P:) digestibility of 3 meat and bone meal samples (MBM-1, MBM-2: , and MBM-3:) for broiler chickens. Four semipurified diets were formulated from each sample to contain graded concentrations of P. The experiment was conducted as a completely randomized design with 6 replicates (6 birds per replicate) per dietary treatment. A total of 432 Ross 308 broilers were assigned at 21 d of age to the 12 test diets. The apparent ileal digestibility coefficient of P was determined by the indicator method, and the linear regression method was used to determine the true P digestibility coefficient. The apparent ileal digestibility coefficient of P in birds fed diets containing MBM-1 and MBM-2 was unaffected by increasing dietary concentrations of P (P > 0.05). The apparent ileal digestibility coefficient of P in birds fed the MBM-3 diets decreased with increasing P concentrations (linear, P < 0.001; quadratic, P < 0. 01). In birds fed the MBM-1 and MBM-2 diets, ileal endogenous P losses were estimated to be 0.049 and 0.142 g/kg DM intake (DMI:), respectively. In birds fed the MBM-3 diets, endogenous P loss was estimated to be negative (-0.370 g/kg DMI). True ileal P digestibility of MBM-1, MBM-2, and MBM-3 was determined to be 0.693, 0.608, and 0.420, respectively. True ileal P digestibility coefficients determined for MBM-1 and MBM-2 were similar (P < 0.05), but were higher (P < 0.05) than that for MBM-3. Total P and true digestible P contents of MBM-1, MBM-2, and MBM-3 were determined to be 37.5 and 26.0; 60.2 and 36.6; and 59.8 and 25.1 g/kg, respectively, on an as-fed basis. PMID:26015585

  2. Management of ileal perforation due to typhoid fever.

    PubMed Central

    Kim, J P; Oh, S K; Jarrett, F

    1975-01-01

    The results of the surgical management of 161 cases of ileal perforation due to typhoid fever are presented. Most were seen after an illness of 2-4 weeks, and because of delays in seeking hospital admission, more than half were explored more than 24 hours after their perforation occurred. All patients were prepared for operation with nasogastric suction, intravenous fluids, and antibiotics. At laparotomy, 80% had considerable quantities of pus and small bowel contents in the peritoneal cavity and the remainder had localized abscesses; there were no instances of localization of the perforation. One hundred three of these patients underwent simple closure of their perforations, while 43 underwent small bowel resection, usually because of multiple perforations. Exteriorization or drainage were performed only in patients too sick to tolerate a more appropriate procedure. The overall mortality was 9.9%. The authors believe that typhoid perforations can best be dealt with at operation. Delay in operative intervention adversely affects the survival rate after surgery. Chloramphenicol is used as the drug of choice. PMID:1119873

  3. 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

  4. Bioadhesive delivery systems for mucosal vaccine delivery.

    PubMed

    Baudner, Barbara C; O'Hagan, Derek T

    2010-12-01

    Mucosal vaccine delivery potentially induces mucosal as well as systemic immune responses and may have advantages particularly for optimal protection against pathogens that infect the host through mucosal surfaces. However, the delivery of antigens through mucosal membranes remains a major challenge due to unfavorable physiological conditions (pH and enzymes) and significant biological barriers, which restrict the uptake of antigens. To improve mucosal vaccine delivery, the use of bioadhesive delivery systems offers numerous advantages, including protection from degradation, increasing concentration of antigen in the vicinity of mucosal tissue for better absorption, extending their residence time, and/or targeting them to sites of antigen uptake. Although some bioadhesives have direct immune stimulating properties, it appears most likely that successful mucosal vaccination will require the addition of vaccine adjuvants for optimal immune responses, particularly if they are to be used in an unprimed population. Thus, complex vaccine formulations and delivery strategies have to be carefully designed to appropriately stimulate immune response for the target pathogen. In addition, careful consideration is needed to define the "best" route for mucosal immunization for each individual pathogen. PMID:21039314

  5. 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

  6. Biology and mucosal immunity to myxozoans.

    PubMed

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

    2014-04-01

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

  7. Biology and Mucosal Immunity to Myxozoans

    PubMed Central

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

    2014-01-01

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

  8. Mucosal Immunosenescence In The Gastrointestinal Tract

    PubMed Central

    Sato, Shintaro; Kiyono, Hiroshi; Fujihashi, Kohtaro

    2014-01-01

    It has been shown that pathogen-specific secretory IgA (SIgA) antibody (Ab) is the major player at mucosal surfaces for host defense. However, alterations in the mucosal immune system occur in advanced aging which results in a failure of induction of SIgA Abs for protection from infectious diseases. Signs of mucosal senescence first appear in the gut immune system. Further, changes in the intestinal microbiota most likely influence mucosal immunity. To overcome the immunological aging decline in mucosal immunity, several adjuvant systems including mucosal dendritic cell (DC) targeting have been shown to be attractive and effective immunological strategies. Similarly, antigen (Ag) uptake-M cells are ideal targets for facilitating Ag-specific mucosal immune responses. However, the numbers of M cells are reduced in aged mice. In this regard, Spi-B, an essential transcription factor for the functional and structural differentiation of M cells could be a potent strategy for the induction of effective mucosal immunity in aging. PMID:25531743

  9. Subcellular compartmentation of glutathione in dicotyledonous plants

    PubMed Central

    Mller, Maria

    2010-01-01

    This study describes the subcellular distribution of glutathione in roots and leaves of different plant species (Arabidopsis, Cucurbita, and Nicotiana). Glutathione is an important antioxidant and redox buffer which is involved in many metabolic processes including plant defense. Thus information on the subcellular distribution in these model plants especially during stress situations provides a deeper insight into compartment specific defense reactions and reflects the occurrence of compartment specific oxidative stress. With immunogold cytochemistry and computer-supported transmission electron microscopy glutathione could be localized in highest contents in mitochondria, followed by nuclei, peroxisomes, the cytosol, and plastids. Within chloroplasts and mitochondria, glutathione was restricted to the stroma and matrix, respectively, and did not occur in the lumen of cristae and thylakoids. Glutathione was also found at the membrane and in the lumen of the endoplasmic reticulum. It was also associated with the trans and cis side of dictyosomes. None or only very little glutathione was detected in vacuoles and the apoplast of mesophyll and root cells. Additionally, glutathione was found in all cell compartments of phloem vessels, vascular parenchyma cells (including vacuoles) but was absent in xylem vessels. The specificity of this method was supported by the reduction of glutathione labeling in all cell compartments (up to 98%) of the glutathione-deficient Arabidopsis thaliana rml1 mutant. Additionally, we found a similar distribution of glutathione in samples after conventional fixation and rapid microwave-supported fixation. Thus, indicating that a redistribution of glutathione does not occur during sample preparation. Summing up, this study gives a detailed insight into the subcellular distribution of glutathione in plants and presents solid evidence for the accuracy and specificity of the applied method. PMID:20186447

  10. Mucosal vaccines: novel strategies and applications for the control of pathogens and tumors at mucosal sites.

    PubMed

    Nizard, Mevyn; Diniz, Mariana O; Roussel, Helene; Tran, Thi; Ferreira, Luis Cs; Badoual, Cecile; Tartour, Eric

    2014-01-01

    The mucosal immune system displays several adaptations reflecting the exposure to the external environment. The efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. In contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors located at mucosal sites as well as systemic response. At least in part, such features can be explained by the compartmentalization of mucosal B and T cell populations that play important roles in the modulation of local immune responses. In the present review, we discuss molecular and cellular features of the mucosal immune system as well as novel immunization approaches that may lead to the development of innovative and efficient vaccines targeting pathogens and tumors at different mucosal sites. PMID:25424921

  11. 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). There was significant correlation of survival with the increase of GSH (P < 0.05). The expression of the GSH-Px and GSTpi enzymes showed no statistically significant correlation with the analyzed variables (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 < 0.05). High GSH immunoexpression was associated with better clinical outcomes. Conclusion Therefore, high expression of the GSH seems to play an important role in the clinical outcome of patients with mammary tumors and suggest its use as prognostic marker. The in vitro doxorubicin treatment significantly reduces the expression of GCLC and GSS genes so we can consider them to be candidates for predictive markers of therapeutic response in mammary cancer. PMID:24565113

  12. Effect of Dietary Exogenous Enzyme Supplementation on Enteric Mucosal Morphological Development and Adherent Mucin Thickness in Turkeys

    PubMed Central

    Ayoola, Ayuub A.; Malheiros, Ramon D.; Grimes, Jesse L.; Ferket, Peter R.

    2015-01-01

    Anti-nutritional factors (ANFs) in feed ingredients can challenge gut health and reduce nutrient utilization. Birds typically activate their innate immune system as a protective response against the adverse effects of ANF, which often involves the secretion of mucin. Although dietary supplementation of exogenous enzymes are commonly used to alleviate the adverse effects of ANF on apparent nutrient digestibility, little is known about how they affect gut health, particularly in relation to the morphological development and mucin secretion of enteric mucosa. We carried out two trials to examine the effect of dietary supplementation of different types of exogenous enzymes on gut health of by accessing the effect of jejunum morphological development and ileal enteric adherent mucin thickness layer in turkeys. Dietary β-mannanase supplementation reduced ileal adherent mucin thickness layer (804 vs 823 μg/g; p < 0.05), while a commercial blend of xylanase, amylase, and protease (XAP) reduced ileal adherent mucin layer thickness (589 vs 740 μg/g; p < 0.05); thus reducing the apparent endogenous loss of nutrients. Both enzyme supplements also affected gut morphological characteristics. In comparison to the control treatment, dietary β-mannanase supplementation improved the jejunum tip width (219 vs 161; p < 0.05), base width (367 vs 300; p < 0.05), surface area (509,870 vs 380, 157; p < 0.05) and villi height/crypt depth ratio (7.49 vs 5.70; p < 0.05), and XAP improved the crypt depth (p < 0.05). In conclusion, dietary supplementation of exogenous enzymes may help alleviate the adverse effects of ANF on nutrient utilization by directly or indirectly removing the mucosal irritation that stimulates enteric mucin secretion. PMID:26664972

  13. Effect of Dietary Exogenous Enzyme Supplementation on Enteric Mucosal Morphological Development and Adherent Mucin Thickness in Turkeys.

    PubMed

    Ayoola, Ayuub A; Malheiros, Ramon D; Grimes, Jesse L; Ferket, Peter R

    2015-01-01

    Anti-nutritional factors (ANFs) in feed ingredients can challenge gut health and reduce nutrient utilization. Birds typically activate their innate immune system as a protective response against the adverse effects of ANF, which often involves the secretion of mucin. Although dietary supplementation of exogenous enzymes are commonly used to alleviate the adverse effects of ANF on apparent nutrient digestibility, little is known about how they affect gut health, particularly in relation to the morphological development and mucin secretion of enteric mucosa. We carried out two trials to examine the effect of dietary supplementation of different types of exogenous enzymes on gut health of by accessing the effect of jejunum morphological development and ileal enteric adherent mucin thickness layer in turkeys. Dietary ?-mannanase supplementation reduced ileal adherent mucin thickness layer (804 vs 823??g/g; p?ileal adherent mucin layer thickness (589 vs 740??g/g; p?mucosal irritation that stimulates enteric mucin secretion. PMID:26664972

  14. Role of thyroxine on postnatal development of ileal active bile salt transport

    SciTech Connect

    Heubi, J.E.

    1986-08-01

    The role of thyroid hormone on the postnatal development of ileal active taurocholate transport uptake was measured by an in vitro incubation technique in Sprague-Dawley rats. In 16-day-old rats treated with pharmacological doses of L-thyroxine ileal active transport appeared precociously whose K/sub m/ was 1.60 +/- 0.48 mM and V/sub app/ was 8.09 +/- 1.14 nmol min mg dry wt , while age-matched shams had only passive diffusion of taurocholate. To determine whether enhanced endogenous secretion of thyroxine was capable of stimulating development of ileal active taurocholate transport, thyrotrophic stimulating hormone (TSH) was given on days 10-13, with uptake measured on day 16. Following TSH treatment, only passive transport for taurocholate was observed in the ileum; uptake rates were consistently higher than those for untreated controls at each study concentration. Thyroidectomy performed at age 14 days with uptake measured at age 21 days did not ablate development of ileal active transport but resulted in a significant reduction in the V/sub app/ and a significant increase in K/sub m/ compared with age-matched controls. Thyroid hormone does not appear to be obligatory for the postnatal development of ileal active taurocholate transport.

  15. Increased epithelial cell proliferation in the ileal pouch mucosa of patients with familial adenomatous polyposis.

    PubMed

    Friederich, P; van Heumen, B W H; Nagtegaal, I D; Berkhout, M; van Krieken, J H J M; Peters, W H M; Nagengast, F M

    2007-09-01

    To eliminate the risk of colorectal cancer in patients with familial adenomatous polyposis (FAP), reconstructive proctocolectomy is performed. Although most colonic mucosa is resected during the ileal pouch anal anastomosis, adenomas and carcinomas may develop in the pouch. This may be caused by altered cell kinetics due to intraluminal changes in the pouch. In 32 patients with FAP, biopsy specimens from the mucosa of the pouch and also of the afferent ileal loop were taken. Tissue sections were immunohistochemically processed with the monoclonal antibodies M30 and MIB-1 to assess apoptotic and proliferative indices, respectively. Cell proliferation was also assessed by a modified sign test. There were no significant differences in apoptotic rates between the mucosa of the pouch and the mucosa of the afferent ileal loop. However, cell proliferation was significantly higher in the mucosa of the pouch vs afferent ileal loop, both by using the quantitative (68.3% vs 61.6%, p = 0.001) and semiquantitative methods (p < 0.05). Our newly developed semiquantitative approach outperformed previously described methods. The higher cell proliferation in the pouch as compared to the afferent ileal loop may contribute to the increased risk for adenomas and carcinomas in the pouch of patients with FAP and emphasizes the need for regular endoscopic surveillance. PMID:17611772

  16. 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

  17. Respiratory mucosal permeability in asthma

    SciTech Connect

    Elwood, R.K.; Kennedy, S.; Belzberg, A.; Hogg, J.C.; Pare, P.D.

    1983-09-01

    The permeability of respiratory mucosa to technetium-labeled diethylenetriamine pentacetic acid (/sup 99m/Tc-DTPA) was measured in 10 clinically stable chronic asthmatics and the results were compared with those in 9 nonasthmatic control subjects. Nonspecific bronchial reactivity was measured using methacholine, and the PC20 was calculated. The intrapulmonary distribution and dose of the inhaled /sup 99m/Tc-DTPA was determined by a gamma camera and the half-life of the aerosolized label in the lung was calculated. The accumulation of radioactivity in the blood was monitored and a permeability index was calculated at 10, 25, and 60 min after aerosolization. Despite marked differences in airway reactivity, no differences in either parameter of permeability could be detected between the asthmatics and the control group. It is concluded that clinically stable asthmatics do not demonstrate increase mucosal permeability to small solutes when compared with normal subjects.

  18. 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

  19. Long-lived cytotoxic T lymphocyte memory in mucosal tissues after mucosal but not systemic immunization.

    PubMed

    Gallichan, W S; Rosenthal, K L

    1996-11-01

    The induction and maintenance of long-term CTL memory at mucosal surfaces may be a critical component of protection against mucosal pathogens and is one goal towards development of effective mucosal vaccines. In these studies we have functionally evaluated short and long-term CTL memory in systemic and respiratory or genital-associated lymphoid tissues following mucosal or systemic routes of immunization. Our results indicate that shortly after immunizing mice with a recombinant adenovirus vector expressing glycoprotein B (gB) of herpes simplex virus (AdgB8), gB-specific CTL memory responses were observed in systemic and mucosal immune compartments regardless of the route of inoculation. In contrast, several months after immunization, anamnestic CTL responses compartmentalized exclusively to mucosal or systemic lymphoid tissues after mucosal or systemic immunization, respectively. Furthermore, the compartmentalized CTL memory responses in mucosal tissues were functionally observed for longer than 1.5 yr after intranasal immunization, and CTL precursor frequencies one year after immunization were comparable to those seen shortly after immunization. Therefore, to our knowledge, this is the first functional demonstration that the maintenance of anti-viral memory CTL in mucosal tissues is dependent on the route of immunization and the time of assessment. These results have important implications for our understanding of the development, maintenance, and compartmentalization of functional T cell memory and the development and evaluation of vaccines for mucosal pathogens, such as HSV and HIV. PMID:8920875

  20. Treatment of oral mucositis due to chemotherapy

    PubMed Central

    Bagán-Sebastián, José V

    2016-01-01

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

  1. Glutathione synthesis in the exocrine pancreas.

    PubMed

    Neuschwander-Tetri, B A; Presti, M E; Wells, L D

    1997-05-01

    Glutathione is essential for cellular cytoprotection, and in the exocrine pancreas, it is required for digestive enzyme synthesis. The purpose of these studies was to measure the capacity of the exocrine pancreas to synthesize glutathione, determine whether the pancreatic transsulfuration pathway has a role in providing cysteine needed for glutathione synthesis, and determine whether the glutathione synthetic capacity of the pancreas responds to pathologically relevant stresses. The activity of gamma-glutamylcysteine synthetase, the key regulatory enzyme for glutathione synthesis, was 3.56 +/- 0.29 mU/mg protein in the pancreas of fed rats, compared to 31 +/- 4 in the liver and 116 +/- 5 in the kidney. Studies using dispersed rat pancreatic acinar cells showed that the exocrine pancreas synthesizes glutathione from precursor amino acids and that the transsulfuration pathway is functionally intact in the pancreas and may serve as an important source of pancreatic cysteine. In mice, pancreatic gamma-glutamylcysteine synthetase activity was induced 37% by corn oil, 77% by ethanol, and 88% by both treatments. Thus, the glutathione synthetic capacity of the pancreas is quantitatively less than that of the kidney or liver, but its key regulatory enzyme responds dynamically to pathologically relevant metabolic stresses, suggesting that glutathione is a key pancreatic cytoprotectant. PMID:9163779

  2. Skeletal muscle glutathione after surgical trauma.

    PubMed Central

    Luo, J L; Hammarqvist, F; Andersson, K; Wernerman, J

    1996-01-01

    OBJECTIVE: The authors investigate the effect of surgical trauma on skeletal muscle concentrations of glutathione in patients undergoing selective abdominal surgery. SUMMARY BACKGROUND DATA: The posttraumatic state is accompanied by characteristic changes in the pattern of free amino acids and a decline of protein synthesis in human skeletal muscle. Glutathione has multiple metabolic functions that are involved in cellular homeostasis. It is unknown how surgical trauma affects the glutathione metabolism of skeletal muscle in surgical patients. METHODS: Eight patients undergoing elective abdominal surgery were investigated. Percutaneous muscle biopsies and blood samples were taken before operation and at 6, 24, and 48 hours after operation. The concentrations of glutathione were determined in muscle tissue, plasma, and whole blood, as well as the concentrations of the related amino acids in muscle and plasma. RESULTS: In skeletal muscle, the levels of both reduced and total glutathione decreased by 40% (p<0.01) at 24 hours and remained low at 48 hours after operation compared with the preoperative values. The glutathione concentration in plasma was 20% lower after operation compared with the concentration before operation (p<0.05). There were no changes at the whole blood levels of glutathione. Tissue glutamate and glutamine decreased significantly after operation (p<0.001), whereas intracellular cysteine and glycine remained unchanged. CONCLUSIONS: Skeletal muscle glutathione deficiency occurs after surgical trauma. This may lead to an increase in the susceptibility to intracellular oxidative injury. PMID:8633921

  3. 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

  4. 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.

  5. Hepatitis viral load correlates to glutathione levels.

    PubMed

    1998-01-01

    Several recent scientific articles have found a direct correlation between Glutathione levels and viral activity for hepatitis B and C. When viral load increases, Glutathione decreases. Researchers from Germany report that adding NAC (N-acetyl cysteine) to HBV producing cells lines can reduce hepatitis viral load 50 fold. Glutathione is used by the liver to help break down toxins. Patients who have chronic infection for more than 90 days should ask their physicians to check their Glutathione levels. A test kit is available from ImmunoSciences Labs; contact information is included. An amino acid, L-Glutamine, can be used with Alpha Lipoic Acid and NAC to increase Glutathione levels. Chlorophyll also offers benefits to people with hepatitis and other infections. Instructions on how to use a special retention enema containing chlorophyll, water, and apple cider vinegar are provided. PMID:11366543

  6. 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. )

    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%).

  7. Mucin output in ileal digesta of pigs fed a protein-free diet.

    PubMed

    Lien, K A; Sauer, W C; Fenton, M

    1997-06-01

    Daily outputs of mucin in ileal digesta were estimated in three barrows fed a protein-free diet while administered either saline (SAI) or a complete amino acid mixture (AAI) intravenously. The water soluble-ethanol precipitable fraction of ileal digesta (crude mucin; CM) was used to estimate the composition of mucin in ileal digesta. This fraction exhibited a carbohydrate composition characteristic of mucin and had a high threonine, serine and proline content (40 mol/100 mol). The proportions of soluble gastric and intestinal mucins, approximately 27 and 73%, respectively, were estimated from the N-acetylglucosamine (GlcNAc)/N-acetylgalactosamine (GalNAc) ratio in CM. The daily outputs of soluble mucin, 2.75 and 3.41 g/day from SAI and AAI pigs (p = 0.13), respectively, were determined from the GalNAc outputs in CM, assuming the above contributions of gastric and intestinal mucins. The estimated soluble mucin outputs accounted for more than 99% of the fucose, galactose, GalNAc and GlcNAc in CM. Total mucin outputs in ileal digesta, 5.32 and 5.65 g/day from SAI and AAI Pigs (p = 0.24), respectively, were determined from the total GalNAc output in digesta, assuming soluble and insoluble mucin had similar compositions. Based on these outputs, mucin represented approximately 30, 7 to 22, 15 and 11% of the endogenous threonine, proline, serine and protein, respectively, in ileal digesta. Approximately 74, 76, 100 and 53% of the fucose, galactose GalNAc and GlcNAc, respectively, in ileal digesta from pigs in this study was attributed to mucin. The results from this study demonstrate the importance of mucin as a source of some endogenous amino acids and carbohydrates. PMID:9246734

  8. Ileal pouch anal anastomosis with modified double-stapled mucosectomy-the experience in China

    PubMed Central

    Zhang, Ya-Jie; Han, Yi; Lin, Mou-Bin; He, Yong-Gang; Zhang, Hao-Bo; Yin, Lu; Huang, Liang

    2013-01-01

    AIM: To investigate the feasibility and long-term functional outcome of ileal pouch-anal anastomosis with modified double-stapled mucosectomy. METHODS: From January 2002 to March 2011, fourty-five patients underwent ileal pouch anal anastomosis with modified double-stapled mucosectomy technique and the clinical data obtained for these patients were reviewed. RESULTS: Patients with ulcerative colitis (n = 29) and familial adenomatous polyposis (n = 16) underwent ileal pouch-anal anastomosis with modified double-stapled mucosectomy. Twenty-eight patients underwent one-stage restorative proctocolectomy, ileal pouch anal anastomosis, protective ileostomy and the ileostomy was closed 4-12 mo postoperatively. Two-stage procedures were performed in seventeen urgent patients, proctectomy and ileal pouch anal anastomosis were completed after previous colectomy with ileostomy. Morbidity within the first 30 d of surgery occurred in 10 (22.2%) patients, all of them could be treated conservatively. During the median follow-up of 65 mo, mild to moderate anastomotic narrowing was occurred in 4 patients, one patient developed persistent anastomotic stricture and need surgical intervention. Thirty-five percent of patients developed at least 1 episode of pouchitis. There was no incontinence in our patients, the median functional Oresland score was 6, 3 and 2 after 1 year, 2.5 years and 5 years respectively. Nearly half patients (44.4%) reported moderate functioning, 37.7% reported good functioning, whereas in 17.7% of patients poor functioning was observed after 1 year. Five years later, 79.2% of patients with good function, 16.7% with moderate function, only 4.2% of patients with poor function. CONCLUSION: The results of ileal pouch anal anastomosis with modified double-stapled mucosectomy technique are promising, with a low complication rate and good long-term functional results. PMID:23483639

  9. Ten Years Clinical Experience with Partial Ileal Bypass in Management of the Hyperlipidemias

    PubMed Central

    Buchwald, Henry; Moore, Richard B.; Varco, Richard L.

    1974-01-01

    The first partial ileal bypass operation specifically for the reduction of plasma lipids was performed by us in 1963. Since then we have operated upon and followed for more than three months 126 hyperlipidemic patients. Clinical metabolic studies, before and after the procedure, have demonstrated a 60% decrease in cholesterol absorption, a 3.8-fold increase in total fecal steroid excretion, a 5.7-fold increase in cholesterol synthesis, a 3-fold increase in cholesterol turnover, and a one-third decrease in the miscible cholesterol pool. Circulating cholesterol levels have been lowered an average 41.1% from the preoperative but postdietary baseline. An average 53% cholesterol reduction has been achieved from a pretreatment baseline using a combination of dietary and surgical management. Plasma triglycerides have been reduced in primary hypertriglyceridemic patients (type IV) an average of 52.6% from their preoperative but postdietary baseline. One patient died in the hospital and there have been 13 late deaths over the past 10 years. Four cases of postoperative bowel obstruction required reoperation. Diarrhea following partial ileal bypass is, as a rule, transistory and not a significant problem. No appreciable weight loss results from partial ileal bypass, which is an obvious distinction from the results of the far more massive jejuno-ileal bypass procedure for obesity. We have not encountered hepatotoxic, lithogenic, or nephrolithiasis complications in our partial ileal bypass patients. Sixty-nine per cent of our patients with preoperative angina pectoris have postoperative improvement or total remission of this symptom complex. Serial appraisal of followup coronary arteriographic studies offers preliminary evidence for lesion regression. It is concluded that partial ileal bypass is the most effective means for lipid reduction available today; it is obligatory in its actions, safe, and associated with minimal side effects. PMID:4416064

  10. Helicobacter pylori vaccine: mucosal adjuvant & delivery systems.

    PubMed

    Sijun, Hu; Yong, Xie

    2009-08-01

    Vaccination, especially mucosal vaccination, is considered to be effective in the management of Helicobacter pylori infections. However, most antigens alone cannot induce immune responses when administered mucosally and need to be co-administered with adjuvants or delivery systems. The current research on the mucosal adjuvant and delivery systems of vaccine against H. pylori, including advantages and disadvantages, mechanisms and applications is discussed in this review. Mutants of cholera toxin (CT) and the heat labile enterotoxin of Escherichia coli (LT), CpG oligodeoxynucleotides, biocompatible and biodegradable polymers, and live attenuated bacterial vectors may be promising adjuvant and delivery systems for H. pylori vaccine. PMID:19797807

  11. Oral mucositis. A complication of radiotherapy

    SciTech Connect

    Rider, C.A. )

    1990-11-01

    Oral mucositis is a complication of head and neck radiotherapy. It is understood what causes the inflammation and what biological tissue changes occur, however, a definite cure for oral mucositis has not yet been found. Supportive treatments, analgesics, antimicrobials and anti-inflammatory agents have been prescribed, none of which has been a thorough measure of treatment. An effective cure for oral mucositis is still in the midst of scientific research. In the interim local palliative treatments will help to alleviate the patients', debilitating symptoms.

  12. Salivary changes in oral mucosal diseases.

    PubMed

    Hassona, Yazan; Scully, Crispian

    2016-02-01

    Saliva is a unique biological fluid that can be easily collected and analyzed with low cost and low morbidity. Therefore, there is a growing attention for using salivary biomarkers in the diagnosis and monitoring of disease progress and response to treatment. Salivary changes have been described in relation to oral mucosal diseases. This article discusses the causes and consequences of salivary hypofunction and presents a review of the literature related to changes in salivary parameters in various oral mucosal diseases and in systemic diseases with possible oral mucosal involvement. PMID:26662486

  13. Palliation of radiation-related mucositis

    SciTech Connect

    Rothwell, B.R.; Spektor, W.S.

    1990-01-01

    Oral mucositis associated with head and neck radiotherapy can substantially hinder completion of cancer therapy. Alleviation of this often severe stomatitis can provide enhanced patient comfort and facilitate appropriate care. A double-blind format was used in a pilot project to measure, against a control rinse, the effectiveness of an oral rinse consisting of hydrocortisone, nystatin, tetracycline, and diphenhydramine in controlling radiation-related mucositis. A combination of clinical evaluation and patient responses to a questionnaire was used to judge the results of the topical medications. Patients using the experimental medication developed less mucositis than did patients in the control group.

  14. Adenocarcinoma of the Ileal Conduit in a Patient Born With Classic Bladder Exstrophy

    PubMed Central

    Ko, Joan S.; Di Carlo, Heather N.; Gupta, Angela D.; Ross, Ashley E.; Eckhauser, Frederic E.; Bivalacqua, Trinity J.

    2013-01-01

    Bladder exstrophy is a rare birth defect that typically requires patients to undergo multiple surgical procedures throughout the course of their childhood. Many ultimately undergo operations that use segments of bowel for the reconstruction and/or augmentation of the urinary tract, which imparts an increased risk of malignancy in these patients. We present the case of a 59-year-old man with a history of bladder exstrophy managed with ureterosigmoidostomies revised to an ileal conduit who developed a large adenocarcinoma in the ileal conduit that extended into small bowel, sigmoid colon, and ureter.

  15. 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

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

    PubMed Central

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

    2009-01-01

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

  17. Mucosal immunity to infection with implications for vaccine development.

    PubMed

    Staats, H F; Jackson, R J; Marinaro, M; Takahashi, I; Kiyono, H; McGhee, J R

    1994-08-01

    The induction of effective mucosal immunity that also provides systemic immunity is a considerable challenge. Over the past two years, efforts to develop novel mucosal vaccine delivery systems to induce mucosal immunity against bacterial and viral diseases, including HIV, have dramatically increased. Here we cite novel vaccines and delivery systems being used to establish effective mucosal immunity. PMID:7946045

  18. Glutathione degradation is a key determinant of glutathione homeostasis.

    PubMed

    Baudouin-Cornu, Peggy; Lagniel, Gilles; Kumar, Chitranshu; Huang, Meng-Er; Labarre, Jean

    2012-02-10

    Glutathione (GSH) has several important functions in eukaryotic cells, and its intracellular concentration is tightly controlled. Combining mathematical models and (35)S labeling, we analyzed Saccharomyces cerevisiae sulfur metabolism. This led us to the observation that GSH recycling is markedly faster than previously estimated. We set up additional in vivo assays and concluded that under standard conditions, GSH half-life is around 90 min. Sulfur starvation and growth with GSH as the sole sulfur source strongly increase GSH degradation, whereas cadmium (Cd(2+)) treatment inhibits GSH degradation. Whatever the condition tested, GSH is degraded by the cytosolic Dug complex (composed of the three subunits Dug1, Dug2, and Dug3) but not by the ?-glutamyl-transpeptidase, raising the question of the role of this enzyme. In vivo, both DUG2/3 mRNA levels and Dug activity are quickly induced by sulfur deprivation in a Met4-dependent manner. This suggests that Dug activity is mainly regulated at the transcriptional level. Finally, analysis of dug2? and dug3? mutant cells shows that GSH degradation activity strongly impacts on GSH intracellular concentration and that GSH intracellular concentration does not affect GSH synthesis rate. Altogether, our data led us to reconsider important aspects of GSH metabolism, challenging notions on GSH synthesis and GSH degradation that were considered as established. PMID:22170048

  19. Mucosal delivery of vaccine antigens and its advantages in pediatrics.

    PubMed

    De Magistris, Maria Teresa

    2006-04-20

    The delivery of vaccines through the mucosal route is very practical, non-invasive and efficacious for the induction of mucosal and systemic immune responses. Appropriately formulated mucosal vaccines can stimulate all arms of the immune system and could be exploited for protection against pathogens that infect the host through the mucosal surfaces as well as those acquired through other routes. There are few available mucosal vaccines so far and these are mainly based on whole microorganisms. The development of new generation mucosal vaccines based on purified protective antigens has been hampered for a long time by the low immunogenicity of soluble antigens and by the lack of safe and efficacious mucosal adjuvants. However, we have now several promising candidate adjuvants and delivery systems for mucosal immunization. In this review I will illustrate the advantages of mucosal vaccination and I will discuss what we still need to develop safe and efficacious mucosal vaccines that would be beneficial especially for young children. PMID:16516335

  20. Microbiota and Mucosal Immunity in Amphibians

    PubMed Central

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

    2015-01-01

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

  1. Microbiota and mucosal immunity in amphibians.

    PubMed

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

    2015-01-01

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

  2. Microparticle vaccine approaches to stimulate mucosal immunisation.

    PubMed

    Brayden, D J; Baird, A W

    2001-08-01

    Entrapment of antigens in biodegradable particles for mucosal immunisation has given successful outcomes in animals, but not as yet in man. Formulations using genuinely stable biocompatible nanoparticles with co-entrapped mucosal adjuvants and/or with surface-conjugated human M-cell-targeting ligands may lead to better uptake of intact antigen by Peyer's patch M cells and delivery to antigen-presenting cells. PMID:11580982

  3. Glutathione and modulation of cell apoptosis.

    PubMed

    Circu, Magdalena L; Aw, Tak Yee

    2012-10-01

    Apoptosis is a highly organized form of cell death that is important for tissue homeostasis, organ development and senescence. To date, the extrinsic (death receptor mediated) and intrinsic (mitochondria derived) apoptotic pathways have been characterized in mammalian cells. Reduced glutathione, is the most prevalent cellular thiol that plays an essential role in preserving a reduced intracellular environment. glutathione protection of cellular macromolecules like deoxyribose nucleic acid proteins and lipids against oxidizing, environmental and cytotoxic agents, underscores its central anti-apoptotic function. Reactive oxygen and nitrogen species can oxidize cellular glutathione or induce its extracellular export leading to the loss of intracellular redox homeostasis and activation of the apoptotic signaling cascade. Recent evidence uncovered a novel role for glutathione involvement in apoptotic signaling pathways wherein post-translational S-glutathiolation of protein redox active cysteines is implicated in the potentiation of apoptosis. In the present review we focus on the key aspects of glutathione redox mechanisms associated with apoptotic signaling that includes: (a) changes in cellular glutathione redox homeostasis through glutathione oxidation or GSH transport in relation to the initiation or propagation of the apoptotic cascade, and (b) evidence for S-glutathiolation in protein modulation and apoptotic initiation. PMID:22732297

  4. Selenium, glutathione peroxidase and other selenoproteins

    SciTech Connect

    Wilhelmsen, E.C.

    1983-01-01

    Selenium, as essential trace element, has long been associated with protein. The essentiality of selenium is partially understood as glutathione peroxidase contains an essential selenocysteine. Glutathione peroxidase has been purified from many tissues including rat liver. An estimated molecular weight of 105,000 was obtained for glutathione peroxidase by comparison to standards. A subunit size of 26,000 was obtained by SDS-gel electrophoresis. Glutathione peroxidase is not the only selenoprotein in the rat. In seven rat tissues examined, there were many different subunit sizes and change groups representing between 9 and 23 selenoproteins. Selenocysteine in glutathione peroxidase accounts for ca. 36% of the selenium in the rat. The mode of synthesis of glutathione peroxidase and the other selenoproteins is not understood. Glutathione peroxidase is strongly and reversibly inhibited by mercaptocarboxylic acids and other mercaptans, including some used as slow-acting drugs for the symtomatic treatment of rheumatoid arthritis. The mechanism and chemistry of this inhibition is discussed. This inhibition may provide a link between selenium and arthritis.

  5. 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

  6. Mucosal Immunology of HIV Infection

    PubMed Central

    Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S.

    2013-01-01

    Summary Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of ‘symbiotic’ intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4+ T-cell responses, binding antibodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Further, immune therapies specifically directed towards boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients. PMID:23772612

  7. Polyamines and Gut Mucosal Homeostasis

    PubMed Central

    Timmons, Jennifer; Chang, Elizabeth T.; Wang, Jian-Ying; Rao, Jaladanki N.

    2012-01-01

    The epithelium of gastrointestinal (GI) mucosa has the most rapid turnover rate of any tissue in the body and its integrity is preserved through the dynamic balance between cell migration, proliferation, growth arrest and apoptosis. To maintain tissue homeostasis of the GI mucosa, the rates of epithelial cell division and apoptosis must be highly regulated by various extracellular and intracellular factors including cellular polyamines. Natural polyamines spermidine, spermine and their precursor putrescine, are organic cations in eukaryotic cells and are implicated in the control of multiple signaling pathways and distinct cellular functions. Normal intestinal epithelial growth depends on the available supply of polyamines to the dividing cells in the crypts, and polyamines also regulate intestinal epithelial cell (IEC) apoptosis. Although the specific molecular processes controlled by polyamines remains to be fully defined, increasing evidence indicates that polyamines regulate intestinal epithelial integrity by modulating the expression of various growth-related genes. In this review, we will extrapolate the current state of scientific knowledge regarding the roles of polyamines in gut mucosal homeostasis and highlight progress in cellular and molecular mechanisms of polyamines and their potential clinical applications. PMID:25237589

  8. A mathematical model of glutathione metabolism

    PubMed Central

    Reed, Michael C; Thomas, Rachel L; Pavisic, Jovana; James, S Jill; Ulrich, Cornelia M; Nijhout, H Frederik

    2008-01-01

    Background Glutathione (GSH) plays an important role in anti-oxidant defense and detoxification reactions. It is primarily synthesized in the liver by the transsulfuration pathway and exported to provide precursors for in situ GSH synthesis by other tissues. Deficits in glutathione have been implicated in aging and a host of diseases including Alzheimer's disease, Parkinson's disease, cardiovascular disease, cancer, Down syndrome and autism. Approach We explore the properties of glutathione metabolism in the liver by experimenting with a mathematical model of one-carbon metabolism, the transsulfuration pathway, and glutathione synthesis, transport, and breakdown. The model is based on known properties of the enzymes and the regulation of those enzymes by oxidative stress. We explore the half-life of glutathione, the regulation of glutathione synthesis, and its sensitivity to fluctuations in amino acid input. We use the model to simulate the metabolic profiles previously observed in Down syndrome and autism and compare the model results to clinical data. Conclusion We show that the glutathione pools in hepatic cells and in the blood are quite insensitive to fluctuations in amino acid input and offer an explanation based on model predictions. In contrast, we show that hepatic glutathione pools are highly sensitive to the level of oxidative stress. The model shows that overexpression of genes on chromosome 21 and an increase in oxidative stress can explain the metabolic profile of Down syndrome. The model also correctly simulates the metabolic profile of autism when oxidative stress is substantially increased and the adenosine concentration is raised. Finally, we discuss how individual variation arises and its consequences for one-carbon and glutathione metabolism. PMID:18442411

  9. The antioxidant master glutathione and periodontal health

    PubMed Central

    Bains, Vivek Kumar; Bains, Rhythm

    2015-01-01

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

  10. 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, 16941713. PMID:22656858

  11. Mitochondrial Glutathione in Diabetic Nephropathy

    PubMed Central

    Lash, Lawrence H.

    2015-01-01

    Although there are many etiologies for diabetic nephropathy (DN), one common characteristic of all cases involves mitochondrial oxidative stress and consequent bioenergetic dysfunction. As the predominant low-molecular-weight, intramitochondrial thiol reductant, the mitochondrial glutathione (mtGSH) pool plays important roles in how this organelle adapts to the chronic hyperglycemia and redox imbalances associated with DN. This review will summarize information about the processes by which this important GSH pool is regulated and how manipulation of these processes can affect mitochondrial and cellular function in the renal proximal tubule. Mitochondria in renal proximal tubular (PT) cells do not appear to synthesize GSH de novo but obtain it by transport from the cytoplasm. Two inner membrane organic anion carriers, the dicarboxylate carrier (DIC; Slc25a10) and 2-oxoglutarate carrier (OGC; Slc25a11) are responsible for this transport. Genetic modulation of DIC or OGC expression in vitro in PT cells from diabetic rats can alter mitochondrial function and susceptibility of renal PT cells to oxidants, with overexpression leading to reversion of bioenergetic conditions to a non-diabetic state and protection of cells from injury. These findings support the mtGSH carriers as potential therapeutic targets to correct the underlying metabolic disturbance in DN. PMID:26239684

  12. 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...

  13. 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; Yalin, 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 Bjrck 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

  14. Transforming a Biliopancreatic Derivation in an Ileal Interposition with a Single Anastomosis.

    PubMed

    Santoro, Sergio; de Aquino, Caio G Gaspar

    2015-08-01

    The biliopancreatic derivation (BPD) is the most powerful bariatric procedure. However, it never became a very popular procedure, except for Italy, because of the high rate of nutritional problems, intense flatulence, and diarrhea. Here, we describe an extremely simple way (just one anastomosis) to revise the BPD, transforming it into an ileal interposition with duodenal exclusion, solving these described problems. PMID:26084252

  15. 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 1562 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. Can a meta-analysis answer the question: is mucosectomy and handsewn or double-stapled anastomosis better in ileal pouch-anal anastomosis?

    PubMed

    Schluender, Stefanie J; Mei, Ling; Yang, Huiying; Fleshner, Phillip R

    2006-10-01

    Although ileal pouch-anal anastomosis (IPAA) is the procedure of choice for polyposis and ulcerative colitis with medically refractory disease or dysplasia, controversy exists concerning whether mucosal preservation with double-stapled (DS) IPAA is superior to mucosectomy and handsewn (HS) IPAA anastomosis for postoperative function. Prospective studies have shown no statistically significant differences. The use of meta-analysis can strengthen statistical power by combining the data from related studies. A meta-analysis was performed to determine whether there was a significant difference in functional and manometric outcome between HS-IPAA and DS-IPAA. Prospective, randomized studies were identified using a literature search. Functional outcome variables included number of normal continence, minor incontinence, nocturnal evacuation, the ability to discriminate flatus from stool, and antidiarrheal medication. Manometric outcomes included postoperative resting and squeeze anal pressures. Four prospective, randomized trials were identified. Of the 184 total patients, the HS-IPAA group included 86 patients (48 men and 38 women) and the DS-IPAA group included 98 patients (49 men and 49 women). There were no significant differences in functional outcome between HS-IPAA and DS-IPAA. In addition, there was no significant difference in sphincter resting and squeeze pressures between the two patient groups. This meta-analysis demonstrates that DS-IPAA offers no advantage in functional or manometric outcome when compared with HS-IPAA. PMID:17058734

  17. 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-α (TNF-α) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-α 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

  18. Measurement of glutathione-protein mixed disulfides

    SciTech Connect

    Livesey, J.C.; Reed, D.J.

    1984-09-01

    The development of a sensitive and highly specific assay for the presence of mixed disulfides between protein thiol groups and endogenous thiols has been undertaken. Previous investigations on the concentrations of glutathione (GSH), glutathione disulfide (GSSG) and protein glutathione mixed disulfides (ProSSG) have been of limited usefulness because of the poor specificity of the assays used. Our assay for these forms of glutathione is based on high performance liquid chromatography (HPLC) and is an extension of an earlier method. After perchloric acid precipitation, the protein sample is washed with an organic solvent to fully denature the protein. Up to a 10-fold increase in GSH released from fetal bovine serum (FBS) protein has been found when the protein precipitate is washed with ethanol rather than ether, as earlier suggested. Similar effects have been observed with an as yet unidentified thiol which elutes in the chromatography system with a retention volume similar to cysteine.

  19. Genetics Home Reference: Glutathione synthetase deficiency

    MedlinePLUS

    ... enzyme ; gene ; glutathione ; hemolytic anemia ; inherited ; molecule ; neurological ; newborn screening ; oxygen ; psychomotor ; recessive ; screening You may find definitions for these and many other terms in the Genetics Home Reference Glossary . See also Understanding Medical Terminology . ...

  20. Nebivolol has protective effect against endothelial and ileal dysfunction due to I/R.

    PubMed

    Soydan, Gray; Ceki, Edip Gven; Tuncer, Meral

    2011-03-01

    In this study, two enantiomers of the drug, L-nebivolol and racemic nebivolol, were used to measure and compare their ability to prevent endothelial dysfunction, disturbed ileal contractility, and ileal injury induced by I/R. The superior mesenteric artery of male Sprague-Dawley rats was occluded for 45 min to induce ischemia, and then the clamp was removed for 60-min reperfusion. Drugs or saline were administered prior to the surgical procedure in the I/R and sham-operated groups. Vasodilation in the third branch of the mesenteric artery was evaluated with a myograph system. Isometric contractions of the ileal segments in response to acetylcholine or electrical field stimulation (EFS) (120 V, 2-ms pulse duration for 5 s, 1-20 Hz) were recorded on a polygraph. Additionally, the ileal segments were examined histopathologically. Acetylcholine-induced relaxation of the mesenteric artery, precontracted by submaximal phenylephrine, markedly decreased after I/R. L-nebivolol pretreatment reversed this relaxation, but racemic nebivolol did not. Contractions induced by both acetylcholine and EFS were significantly reduced after I/R. L-nebivolol, but not racemic nebivolol, prevented this reduction in the acetylcholine-induced contractions. I/R-induced reduction was prevented by L-nebivolol only in response to EFS of 20 Hz. Intestinal I/R caused severe ischemic injury in the rat ileum, which was prevented by L-nebivolol, but not racemic nebivolol. Control responses were not affected by L-nebivolol or racemic nebivolol. These results suggest that L-nebivolol had a protective effect against both endothelial dysfunction of the mesenteric artery and ileal injury induced by intestinal I/R; however, similar effects were not observed for racemic nebivolol. PMID:19922953

  1. Defending the mucosa: adjuvant and carrier formulations for mucosal immunity.

    PubMed

    Lawson, Louise B; Norton, Elizabeth B; Clements, John D

    2011-06-01

    A majority of infectious microorganisms either colonize or cross mucosal surfaces to enter the host. A major goal in vaccine design is to induce a protective, lasting immune response against potential pathogens at mucosal surfaces. In addition, mucosal vaccines can offer needle-free delivery, thereby improving accessibility, safety, and cost-effectiveness. Challenges to successful mucosal vaccination include poor induction of mucosal immunity, limited understanding of protective mechanisms and crosstalk between mucosal compartments, and the availability of safe, effective mucosal adjuvants and delivery systems. This review focuses on some key advances in the field of mucosal vaccinology within the past 2-3 years, including reports on promising new formulations and investigations into the mechanisms of established mucosal adjuvants and/or particulate carrier systems. PMID:21511452

  2. Robot-Assisted Laparoscopic Partial Colpectomy and Intracorporeal Ileal Conduit Urinary Diversion (Bricker) for Cervical Adenocarcinoma Recurrence

    PubMed Central

    Uzan, Jennifer; Cornou, Caroline; Bensaid, Chrazade; Audenet, Franois; Ng, Charlotte; Bats, Anne-Sophie; Lecuru, Fabrice

    2015-01-01

    Ileal conduit urinary diversion (Bricker) is a standard surgical open procedure. The Da Vinci robot allowed precision for this surgical procedure, especially for intracorporeal suturing. Meanwhile, few reports of robot-assisted laparoscopic ileal conduit diversion (Bricker) are described in the literature. We report the case of a 69-year-old patient with a vaginal recurrence of cervical adenocarcinoma associated with vesicovaginal fistula treated by robot-assisted laparoscopic partial colpectomy and ileal conduit urinary diversion (Bricker). The robot-assisted laparoscopic procedure followed all surgical steps of the open procedure. Postoperative period was free of complications. PMID:26634161

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

    PubMed

    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

  4. 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

  5. Thioredoxin and glutathione systems in Plasmodium falciparum.

    PubMed

    Jortzik, Esther; Becker, Katja

    2012-10-01

    Despite a 50% decrease in malaria infections between 2000 and 2010, malaria is still one of the three leading infectious diseases with an estimated 216 million cases worldwide in 2010. More than 90% of all malaria infections were caused by Plasmodium falciparum, a unicellular eukaryotic parasite that faces oxidative stress challenges while developing in Anopheles mosquitoes and humans. Reactive oxygen and nitrogen species threatening the parasite are either endogenously produced by heme derived from hemoglobin degradation or they are from exogenous sources such as the host immune defense. In order to maintain the intracellular redox balance, P. falciparum employs a complex thioredoxin and glutathione system based on the thioredoxin reductase/thioredoxin and glutathione reductase/glutathione couples. P. falciparum thioredoxin reductase reduces thioredoxin and a range of low molecular weight compounds, while glutathione reductase is highly specific for its substrate glutathione disulfide. Since Plasmodium spp. lack catalase and a classical glutathione peroxidase, their redox balance depends on a complex set of five peroxiredoxins differentially located in the cytosol, apicoplast, mitochondria, and nucleus with partially overlapping substrate preferences. Moreover, P. falciparum employs a set of members belonging to the thioredoxin superfamily such as three thioredoxins, two thioredoxin-like proteins, a dithiol and three monocysteine glutaredoxins, and a redox-active plasmoredoxin with largely redundant functions. This review aims at summarizing our current knowledge on the functional redox networks of the malaria parasite P. falciparum. PMID:22939033

  6. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Glutathione test system. 862.1365 Section 862.1365....1365 Glutathione test system. (a) Identification. A glutathione test system is a device intended to measure glutathione (the tripeptide of glycine, cysteine, and glutamic acid) in erythrocytes (red...

  7. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Glutathione test system. 862.1365 Section 862.1365....1365 Glutathione test system. (a) Identification. A glutathione test system is a device intended to measure glutathione (the tripeptide of glycine, cysteine, and glutamic acid) in erythrocytes (red...

  8. Mucosal immunisation: adjuvants and delivery systems.

    PubMed

    Moyle, P M; McGeary, R P; Blanchfield, J T; Toth, I

    2004-10-01

    The mucosal administration of vaccines is an area currently receiving a high level of interest due to potential advantages offered by this technique. These advantages include the ability to administer vaccines without need for needles, thus improving patient compliance with vaccination schedules, and the capacity to induce immune responses capable of preventing infections at the site of acquisition. Despite these advantages a number of limitations exist which currently inhibit our ability to successfully develop new mucosal vaccines. As such, much research is currently focused on developing new adjuvants and delivery systems to overcome these difficulties. However, despite high levels of interest in this area, relatively few mucosal vaccine candidates have successfully progressed to human clinical trials. In the review that follows, we aim to provide the reader with an overview of the immune system with respect to induction of mucosal immune responses. Furthermore, the review provides an overview of a number of microbial (bacterial toxins, CpG DNA, cytokines/chemokines, live vectors, and virus like particles) and synthetic (microspheres, liposomes, and lipopeptides) strategies that have been investigated as adjuvants or delivery systems for mucosal vaccine development, with a focus on the delivery of vaccines via the oral route. PMID:16305400

  9. Inborn errors in the metabolism of glutathione

    PubMed Central

    Ristoff, Ellinor; Larsson, Agne

    2007-01-01

    Glutathione is a tripeptide composed of glutamate, cysteine and glycine. Glutathione is present in millimolar concentrations in most mammalian cells and it is involved in several fundamental biological functions, including free radical scavenging, detoxification of xenobiotics and carcinogens, redox reactions, biosynthesis of DNA, proteins and leukotrienes, as well as neurotransmission/neuromodulation. Glutathione is metabolised via the gamma-glutamyl cycle, which is catalyzed by six enzymes. In man, hereditary deficiencies have been found in five of the six enzymes. Glutathione synthetase deficiency is the most frequently recognized disorder and, in its severe form, it is associated with hemolytic anemia, metabolic acidosis, 5-oxoprolinuria, central nervous system (CNS) damage and recurrent bacterial infections. Gamma-glutamylcysteine synthetase deficiency is also associated with hemolytic anemia, and some patients with this disorder show defects of neuromuscular function and generalized aminoaciduria. Gamma-glutamyl transpeptidase deficiency has been found in patients with CNS involvement and glutathionuria. 5-Oxoprolinase deficiency is associated with 5-oxoprolinuria but without a clear association with other symptoms. Dipeptidase deficiency has been described in one patient. All disorders are very rare and inherited in an autosomal recessive manner. Most of the mutations are leaky so that many patients have residual enzyme activity. Diagnosis is made by measuring the concentration of different metabolites in the gamma-glutamyl cycle, enzyme activity and in glutathione synthetase and gamma-glutamylcysteine synthetase deficiency, also by mutation analysis. Prenatal diagnosis has been preformed in glutathione synthetase deficiency. The prognosis is difficult to predict, as few patients are known, but seems to vary significantly between different patients. The aims of the treatment of glutathione synthesis defects are to avoid hemolytic crises and to increase the defense against reactive oxygen species. No treatment has been recommended for gamma-glutamyl transpeptidase, 5-oxoprolinase and dipeptidase deficiency. PMID:17397529

  10. Novel vaccine development strategies for inducing mucosal immunity.

    PubMed

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

    2012-03-01

    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. 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

  12. Effect of xylanases on ileal viscosity, intestinal fiber modification, and apparent ileal fiber and nutrient digestibility of rye and wheat in growing pigs.

    PubMed

    Lrke, H N; Arent, S; Dalsgaard, S; Bach Knudsen, K E

    2015-09-01

    Two experiments were performed to study the effect of xylanase on ileal extract viscosity, in vivo fiber solubilization and degradation, and apparent ileal digestibility (AID) of fiber constituents, OM, CP, starch, and crude fat in rye and wheat in ileal-cannulated pigs. In Exp. 1, coarse rye without (NX) or with addition of xylanase from Aspergillus niger (AN), (BS), or (TR) was fed to 8 ileal-cannulated barrows (initial BW 30.9 0.3 kg) for 1 wk each according to a double 4 4 Latin square design. In Exp. 2, fine rye, fine wheat, and coarse wheat with or without a combination of xylanase from and were fed to 6 ileal-cannulated barrows (initial BW 33.6 0.5 kg) for 1 wk according to a 6 6 Latin square design with a 2 3 factorial arrangement of enzyme and cereal matrix. Chromic oxide (0.2%) was used as an inert marker. Ileal effluent was collected for 8 h on d 5 and 7 and pooled for analysis. In Exp. 1, TR reduced intestinal viscosity of pigs fed rye from 9.3 mPas in the control diet (NX) to 6.0 mPas ( < 0.001), whereas AN and BS had no effect. None of the enzymes changed the concentration of total arabinoxylan, high-molecular-weight arabinoxylan (HMW-AX), or arabinoxylan oligosaccharides (AXOS) in the liquid phase of digesta. In Exp. 2, the enzyme combination reduced intestinal viscosity for all 3 cereal matrices ( < 0.05), but the viscosity was much higher with fine rye (7.6 mPas) than with fine and coarse wheat (<1.7 mPas). Simultaneously, the total concentration of arabinoxylan in the liquid phase of digesta increased by 82.4% in fine wheat ( < 0.002) and by 45.9% in coarse wheat ( < 0.006), and AXOS increased 16-fold with enzyme addition. Similar effects of enzyme were not seen with rye. The concentration of xylooligosaccharides in the liquid phase of digesta increased with enzyme addition, but for xylose, it was only significant for wheat, for which it increased 3.9-fold ( < 0.001). None of the xylanases affected AID of arabinoxylan of rye in Exp. 1. In Exp. 2, the enzyme combination increased AID of arabinoxylan by 91% to 107% ( < 0.001) across cereal matrices. Enzyme addition did not affect AID of nutrients in any of the experiments except for a higher starch and crude fat digestibility of fine wheat with enzyme addition ( < 0.012) in Exp. 2. Collectively, the results suggest that xylanase is more efficient in degrading arabinoxylan from wheat than from rye. PMID:26440332

  13. Subsequent Adenomas of Ileal Pouch and Anorectal Segment after Prophylactic Surgery for Familial Adenomatous Polyposis

    PubMed Central

    M'Koma, A.E.; Herline, A.J.; Adunyah, S.E.

    2014-01-01

    Familial adenomatous polyposis (FAP) is an autosomally dominant disease characterized by the early development of colorectal adenomas and carcinoma in untreated patients. Patients with FAP may develop rectal cancer at their initial presentation (primary) or after prophylactic surgery (secondary). Controversies exist regarding which surgical procedure represents the best first-line treatment. The options for FAP are ileorectal anastomosis (IRA) or a restorative proctocolectomy (RPC) with either a handsewn or a stapled ileal pouch-anal anastomosis (IPAA), with or without mucosectomy. The purpose of these surgeries is to stop progression to an adenoma-cancer sequence by eradicating the colon, a disease prone organ. Unfortunately, these surgical procedures, which excise the entire colon and rectum while maintaining transanal fecal continence, do not guarantee that patients still won't develop adenomas. Based on the available literature, we therefore reviewed reported incidences of pouch-related adenomas that occurred post prophylactic surgery for FAP. The review consists of a collection of case, descriptive, prospective and retrospective reports. Objectives To provide available data on the natural history of subsequent adenomas after prophylactic surgery (by type) for FAP. Methods A review was conducted of existing case, descriptive, prospective and retrospective reports for patients undergoing prophylactic surgery for FAP (1975 August, 2013). In each case, the adenomas were clearly diagnosed in one of the following: the ileal pouch mucosa (above the ileorectal anastomosis), within the anorectal segment (ARS) below the ileorectal anastomosis, or in the afferent ileal loop. Results A total of 515 (36%) patients with pouch-related adenomas have been reported. Two hundred and eleven (211) patients had adenomas in the ileal pouch mucosa, 295 had them in the ARS and in 9 were in the afferent ileal loop. Patients with pouch adenomas without dysplasia or cancer were either endoscopically polypectomized or were treated with a coagulation modality using either a Nd:Yag laser or argon plasma coagulation (as indicated). Patients with dysplastic pouch adenomas or pouch adenomas with cancer had their pouch excised (pouchectomy). Conclusion In patients with FAP treated with IRA or RPC with IPAA, the formation of adenomas in the pouch-body mucosa or ARS/anastomosis and in the afferent ileal loop is apparent. Because of risks for adenoma recurrence, a life time endoscopic pouch-surveillance is warranted. PMID:24817992

  14. Techniques and technologies to maximize mucosal exposure.

    PubMed

    Moons, Leon M G; Gralnek, Ian M; Siersema, Peter D

    2015-04-01

    Performing high-quality colonoscopy is one of the important goals of gastroenterology practices and requires achieving a high level of bowel cleansing, performing good and safe polypectomy, and detecting all polyps present in the colon. This article summarizes currently available techniques and technologies to maximize mucosal visualization. Several maneuvers can be applied during insertion and withdrawal of the colonoscope to optimize mucosal visualization and decrease the number of missed polyps. Newly developed technologies support the endoscopist in the detection of polyps. Each technique is reviewed, with emphasis on the impact on colorectal polyp detection. PMID:25839682

  15. Glutathione: a key player in autoimmunity.

    PubMed

    Perricone, Carlo; De Carolis, Caterina; Perricone, Roberto

    2009-07-01

    Increasing attention in the physiopathology of inflammatory/immunomediated diseases has been focused on the role of reactive oxygen species (ROS), oxygen-based molecules possessing high chemical reactivity and produced by activated neutrophils during the inflammatory response. During chronic inflammation, when sustained production of ROS occurs, antioxidant defences can weaken, resulting in a situation termed oxidative stress. Moreover, antioxidant defence systems have been demonstrated to be constitutively lacking in patients affected with chronic degenerative diseases, especially inflammatory/immunomediated. Glutathione, a tripeptide, is the principal component of the antioxidant defence system in the living cells. Glutathione has been demonstrated to have diverse effects on the immune system, either stimulating or inhibiting the immunological response in order to control inflammation. The study of interactions between glutathione and the immune system has attracted many investigators. Altered glutathione concentrations may play an important role in many autoimmune pathological conditions prevalently elicited, detrimed and maintained by inflammatory/immune response mediated by oxidative stress reactions. The role of glutathione in autoimmunity will be reviewed herein. PMID:19393193

  16. Orally administered emu oil decreases acute inflammation and alters selected small intestinal parameters in a rat model of mucositis.

    PubMed

    Lindsay, Ruth J; Geier, Mark S; Yazbeck, Roger; Butler, Ross N; Howarth, Gordon S

    2010-08-01

    Mucositis resulting from cancer chemotherapy is a serious disorder of the alimentary tract. Emu oil has demonstrated anti-inflammatory properties in animal models of arthritis and wound healing; however, its effects on the intestine remain unknown. We investigated emu oil for its potential to decrease the severity of mucositis in a rat model. Female Dark Agouti rats (110-150 g) were orogastrically gavaged with emu oil (0.5 or 1 ml) or water (1 ml) for 5 d before intraperitoneal injection of 5-fluorouracil (5-FU, 150 mg/kg) or saline (control), and this was continued up to the day of sacrifice (48, 72 and 96 h post 5-FU administration). Histological (villus height, crypt depth (CD) and disease severity score) and biochemical (myeloperoxidase (MPO) activity) parameters were determined in intestinal tissues collected at sacrifice. Sucrase activity in vivo was quantified by the sucrose breath test. Activated neutrophil activity (MPO) in the ileum was significantly decreased by emu oil (0.5 ml, 451 (sem 168) U/g and 1 ml, 503 (sem 213) U/g) compared with 5-FU-treated controls (1724 (sem 431) U/g) 96 h post 5-FU administration. There were also significant increases in CD (152 (sem 8) microm) in the ileum of rats that received 1 ml emu oil at 96 h compared with 5-FU-treated controls (CD (106 (sem 12) microm)). Emu oil did not affect sucrase activity. Emu oil decreased acute ileal inflammation, and improved mucosal architecture in the intestine during recovery from chemotherapy in rats. Further studies investigating the potential benefits of emu oil as a nutritional supplement for the treatment of intestinal disorders are indicated. PMID:20377926

  17. Bcl-2/caspase 3 mucosal imbalance favors T cell resistance to apoptosis in dogs with inflammatory bowel disease.

    PubMed

    Jergens, A; Young, J; Moore, D; Wang, C; Hostetter, J; Augustine, L; Allenspach, K; Schmitz, S; Mosher, C

    2014-04-15

    Canine idiopathic inflammatory bowel disease (IBD) is believed to result from complex interplay between genetic, microbial, and immunologic factors. Abnormal cell death by apoptosis may result in the persistence of activated intestinal T cells that contribute to mucosal inflammation and clinical severity. To test this hypothesis, we investigated the mucosal expression of pro- and anti-apoptotic proteins in different intestinal compartments and their association with inflammatory indices in dogs with IBD. Apoptosis of lamina propria (LP) T cells in duodenal, ileal, and colonic tissues in control and IBD dogs was analyzed by caspase 3/Bcl-2 immunohistochemistry and TUNEL assays. Densities and distributions of LP caspase 3 and Bcl-2 cells were correlated to histopathologic lesions and the clinical activity index (CIBDAI). Compared to control tissues, IBD dogs had significantly (P<0.01) fewer caspase 3 cells in colonic mucosa. Double immunostaining identified the majority of apoptotic cells as TUNEL(+)/caspase 3(+). Within intestinal mucosa of IBD dogs, there were significantly greater numbers of Bcl-2 cells at the apical and basilar villus in the duodenum as compared to the colon and to the apical and basilar villus in the ileum (P<0.001 for all comparisons). There were significantly greater numbers of Bcl-2 cells at the apical and basilar villus of the duodenum but significantly fewer numbers of Bcl-2 cells at the apical villus of the ileum in IBD dogs compared with controls (P<0.001, P<0.001, and P<0.02, respectively). There was a significant association between the number of Bcl-2 cells in the duodenum of IBD dogs and the CIBDAI (P<0.001 each for mild, moderate and severe clinical IBD). In conclusion, apoptosis of T lymphocytes varies within intestinal compartments of dogs with IBD. Mucosal imbalance of Bcl-2/caspase 3 expression favors T cell resistance to apoptosis which may contribute to T cell accumulation and chronic intestinal inflammation, similar to human IBD. PMID:24495616

  18. Strategies for optimizing targeting and delivery of mucosal HIV vaccines.

    PubMed

    Ahlers, Jeffrey D; Belyakov, Igor M

    2009-10-01

    Effective frontline defenses against HIV-1 will require targeting vaccines to mucosal tissue in order to induce alphabeta CD8(+) lymphocytes in mucosal effector sites (lamina propria and intraepithelial compartment) as well as antibody secreting plasma cells that can neutralize and limit free virus. A concerted second wave of assault against the virus will require the activation and recruitment of antigen specific memory CD4(+) and CD8(+) T cells in mesenteric lymph nodes and distal secondary lymphoid organs. New delivery strategies targeting the "right" DC subsets in combination with delivery of mucosal adjuvants and innate signals for activating DC will be essential for mucosal vaccines in order to circumvent the naturally tolerogenic environment and the induction of Tregs. Mucosal delivery of antigen in combination with inflammatory signals has been shown to empower systemic immunization by directing responses to mucosal sites for imprinting optimum mucosal memory. Here, we discuss novel vaccine strategies and adjuvants for optimizing mucosal delivery of HIV vaccines. PMID:19609978

  19. Blood selenium concentrations and glutathione peroxidase activity.

    PubMed Central

    Lloyd, B; Robson, E; Smith, I; Clayton, B E

    1989-01-01

    Selenium concentrations in children and teenagers without a metabolic disorder eating normal diets (group 1), and young patients with classical phenylketonuria and milder forms of hyperphenylalaninaemia being treated with a diet low in natural protein (group 2) were investigated. There was a strong correlation between blood selenium concentration and age in children in group 1 up to 10 years of age. Blood selenium concentrations and glutathione peroxidase activities were significantly lower in the patients who were receiving diets containing reduced amounts of natural protein, and the differences were more than would be expected for age. When the concentrations of selenium in blood from groups 1 and 2 were compared with glutathione peroxidase activity, a strong association was found when blood selenium concentrations were below 1.26 mumol/l. Reduction in glutathione peroxidase activity may be harmful in the long term, and the addition of selenium to therapeutic diets is recommended. PMID:2705797

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

    PubMed Central

    Mosińska, Paula; Fichna, Jakub; Storr, Martin

    2015-01-01

    Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation-associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipation-related symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation. PMID:26139989

  1. Auto-inflammatory diseases in ileal pouch patients with NOD2/CARD15 mutations

    PubMed Central

    Seril, Darren N.; Yao, Qingping; Shen, Bo

    2016-01-01

    Pouchitis is common in ulcerative colitis patients undergoing total proctocolectomy with ileal pouch-anal anastomosis, and chronic antibiotic-refractory pouchitis occurs in a subgroup of the patients. Auto-inflammatory diseases are characterized by systemic inflammation, manifesting as periodic fever, rash, arthritis, and serositis. We describe two cases with ulcerative colitis and an ileal pouch, who presented with extra-intestinal manifestations and genetic features atypical for inflammatory bowel disease alone. Case 1 had a spectrum of clinical manifestations including refractory pouchitis, intermittent fevers, polyarthralgia, and pericarditis. Case 2 presented with oral ulcers, migratory oligoarthritis, and periodic papular rash. Genetic testing in both cases revealed mutations of the NOD2/CARD15 gene, including the IVS8+158 mutation commonly detected among patients with NOD2-associated auto-inflammatory disease. Both of the patients demonstrated clinical improvement of these diverse systemic complaints following treatment with immunosuppressive and anti-inflammatory therapies. PMID:25313006

  2. Robotic Assisted Laparoscopic Prostatectomy in Men with Proctocolectomy and Restorative Ileal Pouch-Anal Anastomosis

    PubMed Central

    Leapman, Michael; Kwon, Young Suk; Collingwood, Shemille A.; Chin, Edward; Katsigeorgis, Maria; Hobbs, Adele R.; Samadi, David B.

    2014-01-01

    We conducted a retrospective chart review of robotic prostatectomies done by a single surgeon between 2003 and 2012. During that time period, we identified two patients within the year 2012, with ileal pouch-anal anastomosis (IPPA) who also underwent robotic prostatectomies. The demographics and postoperative characteristics of the two patients were assessed. In both patients, prostatectomy, bilateral nerve sparing, and pelvic lymphadenectomy were successfully performed and the integrity of ileal pouch was maintained. There was a mean surgical time of 144.5 minutes, and an average estimated blood loss was 125?mL. Both patients were discharged on the second day postoperatively. In both patients there was a Gleason upgrade to 3 + 4, with negative margins, and preservation of fecal and urinary continence by their six-month followup. Owing to surgical modifications, these two surgeries represent the first successful robotic prostatectomies in patients with a J-pouch. PMID:24653856

  3. Plant-derived antigens as mucosal vaccines.

    PubMed

    Mason, H S; Herbst-Kralovetz, M M

    2012-01-01

    During the last two decades, researchers have developed robust systems for recombinant subunit vaccine production in plants. Stably and transiently transformed plants have particular advantages that enable immunization of humans and animals via mucosal delivery. The initial goal to immunize orally by ingestion of plant-derived antigens has proven difficult to attain, although many studies have demonstrated antibody production in both humans and animals, and in a few cases, protection against pathogen challenge. Substantial hurdles for this strategy are low-antigen content in crudely processed plant material and limited antigen stability in the gut. An alternative is intranasal delivery of purified plant-derived antigens expressed with robust viral vectors, especially virus-like particles. The use of pattern recognition receptor agonists as adjuvants for mucosal delivery of plant-derived antigens can substantially enhance serum and mucosal antibody responses. In this chapter, we briefly review the methods for recombinant protein expression in plants, and describe progress with human and animal vaccines that use mucosal delivery routes. We do not attempt to compile a comprehensive list, but focus on studies that progressed to clinical trials or those that showed strong indications of efficacy in animals. Finally, we discuss some regulatory concerns regarding plant-based vaccines. PMID:21811930

  4. Oral Mucositis: understanding the pathology and management

    PubMed Central

    Georgiou, M; Patapatiou, G; Domoxoudis, S; Pistevou-Gompaki, K; Papanikolaou, A

    2012-01-01

    Oral Mucositis is a common complication of cancer therapy which may limit the completion of treatment and affect the quality of life of the patient. As we have come to understand its pathogenesis new developments in its management and prevention have allowed us minimize this side effect. PMID:23935285

  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. 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 = 66.93.8 kg) surgically fitted with a T-cannula at the distal ileum were allotted to a replicated 33 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

  7. Ileo-ileal knotting as an uncommon cause of acute intestinal obstruction

    PubMed Central

    Abebe, Engida; Asmare, Biruhtesfa; Addise, Abebe

    2015-01-01

    Small bowel obstruction (SBO) is one of the most common acute surgical conditions that require urgent evaluation and treatment. Several common causes are known in the general surgical practice, and the causes are different in the developing and developed world. In this article, we present a case of an acute SBO secondary to ileo-ileal knotting in a 50 years old Ethiopian female patient. The diagnostic difficulty and the need for urgent treatment of the condition are discussed. PMID:26251466

  8. 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 (Ω) was performed with continent diversion. At the 30-month follow-up, there was no complication in clean intermittent catheterization. PMID:25844102

  9. Use of the Memokath Urethral Stent in the management of ileal conduit stomal stenosis

    PubMed Central

    Pan, Tzong-Yang; Al-Sameraaii, Ahmad

    2015-01-01

    Intoduction Ileal conduit stomal stenosis is a difficult complication to manage. Definitive treatment usually requires refashioning or a reconstruction of the conduit. There remains a need for minimally invasive procedures that can restore function to the stoma while avoiding the risks associated with a significant surgical procedure. This case illustrates a novel approach to the management of this complication. Presentation of case An 84 year old female with muscle-invasive bladder cancer underwent cystectomy with formation of an ileal conduit urinary diversion system. Her recovery was complicated by stomal stenosis leading to recurrent urinary tract infections. The Memokath Stent 045 is a thermo-expandable nickeltitanium stent designed for treatment of urethral strictures. The stent was inserted into the stoma under direct vision without the need for general anaesthesia or intraoperative radiography. The conduit remains patent 12 months after insertion and the metal stent showed no evidence of migration, calcification, oxidation or degradation. Discussion The use of a thermo-expandable nickeltitanium stent is able to provide the patency required to treat ileal conduit stomal stenosis. In this case, insertion of the stent was a simple procedure and no adverse events or degradation of the stent was identified at 12 months after insertion. The need for a significant surgical procedure such as a refashioning or reconstruction was avoided and general anaesthesia was not required to perform the procedure. Conclusion This case report highlights the possibility of using the thermo-expandable Memokath Stent 045 as an alternative to the long-term management of ileal conduit stomal stenosis. PMID:26745318

  10. 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

  11. Glutathione Transferase (GST)-Activated Prodrugs

    PubMed Central

    Ruzza, Paolo; Calderan, Andrea

    2013-01-01

    Glutathione transferase (formerly GST) catalyzes the inactivation of various electrophile-producing anticancer agents via conjugation to the tripeptide glutathione. Moreover, several data link the overexpression of some GSTs, in particular GSTP1-1, to both natural and acquired resistance to various structurally unrelated anticancer drugs. Tumor overexpression of these proteins has provided a rationale for the search of GST inhibitors and GST activated cytotoxic prodrugs. In the present review we discuss the current structural and pharmacological knowledge of GST-activated cytotoxic compounds. PMID:24300447

  12. 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

  13. Mucosal immunity: implications for vaccine development.

    PubMed

    Holmgren, J; Czerkinsky, C; Lycke, N; Svennerholm, A M

    1992-02-01

    The mucosal surfaces in e.g. the gastrointestinal, respiratory and urogenital tracts represent a very large exposure area to exogenous agents including microorganisms. Not surprising, therefore, those mucosal tissues are defended by a local immune system with properties and functions that in many respects are separate from the systemic immune system. The intestine is the largest immunological organ in the body. It comprises 70-80% of all immunoglobulin-producing cells and produces more secretory IgA (SIgA) (50-100 mg/kg body weight/day) than the total production of IgG in the body (ca. 30 mg/kg/day). The local immune system of the gut has two main functions: to protect against enteric infections, and to protect against uptake of and/or harmful immune response to undergraded food antigens. The best known entity providing specific immune protection for the gut is the SIgA system. The resistance of SIgA against normal intestinal proteases makes antibodies of this isotype uniquely well suited to protect the intestinal mucosal surface. The main protective function of SIgA antibodies is the "immune exclusion" of bacterial and viral pathogens, bacterial toxins and other potentially harmful molecules. SIgA has also been described to mediate antibody-dependent T cell-mediated cytotoxicity (ADCC), and to interfere with the utilization of necessary growth factors for bacterial pathogens in the intestinal environment, such as iron. It is now almost axiomatic that in order to be efficacious, vaccines against enteric infection must be able to stimulate the local gut mucosal immune system, and that this goal is usually better achieved by administering the vaccines by the oral route rather than parenterally. Based on the concept of a common mucosal immune system through which activated lymphocytes from the gut can disseminate immunity also to other mucosal and glandular tissues there is currently also much interest in the possibility to develop oral vaccines against e.g. infections in the respiratory and urogenital tracts. It has previously been widely assumed that only live vaccines would efficiently stimulate a gut mucosal immune response. However, an oral cholera vaccine, composed of the nontoxic B subunit of cholera toxin in combination with killed whole cell (WC) cholera vibrios has been shown to stimulate a strong intestinal SIgA antibody response associated with long-lasting protection against cholera. We have used this new cholera subunit vaccine and developed ELISPOT methods for examining at the clonal B and T cell level the dynamics of intestinal and extra-intestinal immune responses in humans after enteric immunizations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1587541

  14. Mucosal vaccines: non toxic derivatives of LT and CT as mucosal adjuvants.

    PubMed

    Pizza, M; Giuliani, M M; Fontana, M R; Monaci, E; Douce, G; Dougan, G; Mills, K H; Rappuoli, R; Del Giudice, G

    2001-03-21

    Most vaccines are still delivered by injection. Mucosal vaccination would increase compliance and decrease the risk of spread of infectious diseases due to contaminated syringes. However, most vaccines are unable to induce immune responses when administered mucosally, and require the use of strong adjuvant on effective delivery systems. Cholera toxin (CT) and Escherichia coli enterotoxin (LT) are powerful mucosal adjuvants when co-administered with soluble antigens. However, their use in humans is hampered by their extremely high toxicity. During the past few years, site-directed mutagenesis has permitted the generation of LT and CT mutants fully non toxic or with dramatically reduced toxicity, which still retain their strong adjuvanticity at the mucosal level. Among these mutants, are LTK63 (serine-to-lysine substitution at position 63 in the A subunit) and LTR72 (alanine-to-arginine substitution at position 72 in the A subunit). The first is fully non toxic, whereas the latter retains some residual enzymatic activity. Both of them are extremely active as mucosal adjuvants, being able to induce very high titers of antibodies specific for the antigen with which they are co-administered. Both mutants have now been tested as mucosal adjuvants in different animal species using a wide variety of antigens. Interestingly, mucosal delivery (nasal or oral) of antigens together with LTK63 or LTR72 mutants also conferred protection against challenge in appropriate animal models (e.g. tetanus, Helicobacter pylori, pertussis, pneumococci, influenza, etc). In conclusion, these LTK63 and LTR72 mutants are safe adjuvants to enhance the immunogenicity of vaccines at the mucosal level, and will be tested soon in humans. PMID:11257389

  15. Ileal and total tract digestibility of wet and dried wheat distillers grain products in growing pigs.

    PubMed

    Lyberg, K; Borling, J; Lindberg, J E

    2012-12-01

    The apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of nutrients were evaluated in 2 commercially available products: wheat (Triticum aestivum) wet distillers grain with solubles (WDGS) and wheat dried distillers grain with solubles (DDGS). Two diets included (DM basis) 50% basal diet with either 50% WDGS (W) or 50% DDGS (D). The basal diet included corn (Zea mays) starch, sugar, vitamins, and minerals. Seven castrated male pigs with post valve T-cecum cannulas were fed the diets according to a changeover design during two 14-d periods. In a pre- and postperiod, casein was given as the only protein source with the basal diet to estimate endogenous losses of N and AA for calculation of standardized ileal digestibility (SID). The AID of OM did not differ between diets, but ATTD of OM was higher (P < 0.05) for diet W. The AID (76.2 vs. 68.9%), SID, and ATTD of CP was higher (P < 0.05) in diet W than diet D. The SID for Lys (75.7 vs. 51.8%) and Met (75.8 vs. 70.1%) was higher (P < 0.01) in WDGS than DDGS. In conclusion, drying of wheat distillers grain products can markedly lower ileal digestibility of Lys and Met whereas negative effects on energy value are small. PMID:23365306

  16. Surgical Audit of Patients with Ileal Perforations Requiring Ileostomy in a Tertiary Care Hospital in India

    PubMed Central

    Verma, Hemkant; Pandey, Siddharth; Sheoran, Kapil Dev; Marwah, Sanjay

    2015-01-01

    Introduction. Ileal perforation peritonitis is a frequently encountered surgical emergency in the developing countries. The choice of a procedure for source control depends on the patient condition as well as the surgeon preference. Material and Methods. This was a prospective observational study including 41 patients presenting with perforation peritonitis due to ileal perforation and managed with ileostomy. Demographic profile and operative findings in terms of number of perforations, site, and size of perforation along with histopathological findings of all the cases were recorded. Results. The majority of patients were male. Pain abdomen and fever were the most common presenting complaints. Body mass index of the patients was in the range of 15.4–25.3 while comorbidities were present in 43% cases. Mean duration of preoperative resuscitation was 14.73 + 13.77 hours. Operative findings showed that 78% patients had a single perforation; most perforations were 0.6–1 cm in size and within 15 cm proximal to ileocecal junction. Mesenteric lymphadenopathy was seen in 29.2% patients. On histopathological examination, nonspecific perforations followed by typhoid and tubercular perforations respectively were the most common. Conclusion. Patients with ileal perforations are routinely seen in surgical emergencies and their demography, clinical profile, and intraoperative findings may guide the choice of procedure to be performed. PMID:26247059

  17. Right hemicolectomy and ileal resection with primary reanastomosis for irradiation injury of the terminal ileum

    SciTech Connect

    Hoskins, W.J.; Burke, T.W.; Weiser, E.B.; Heller, P.B.; Grayson, J.; Park, R.C.

    1987-02-01

    Injury to the small intestine from pelvic irradiation increases in frequency when extended treatment fields are utilized and when radiation therapy follows a major abdominal operation. Recommended surgical correction of such injury has been intestinal bypass to avoid the excessive morbidity and mortality from anastamotic leaks associated with primary resection and anastomosis. Since 1980, eight patients with extensive ileal injury secondary to irradiation have been seen at the Naval Hospital Bethesda, Maryland. All patients had previously undergone an abdominal operation and three patients had irradiation utilizing extended fields. In all cases, right hemicolectomy and extended ileal resection were performed with primary anastamosis of the ileum to the ascending colon or the transverse colon. Operating time averaged 4 1/2 hr utilizing hand closure anastomoses and 2 1/2 hr with stapled anastomoses. All patients received postoperative hyperalimentation and six of eight patients received preoperative hyperalimentation. One operative death occurred in a patient with intestinal perforation who required multiple resections. The remaining seven patients experienced no serious complications and had rapid return of bowel function. Our experience indicates that wide ileal resection with right hemicolectomy and primary reanastomosis is an acceptable alternative to intestinal bypass for the treatment of severe irradiation injury, especially when performed with gastrointestinal stapling devices.

  18. Mitomycin-C suppresses mucus secretion in an ileal neobladder rat model

    PubMed Central

    FAN, WEIWEI; YU, YANG; SHU, JUNJIE; MING, HAO; LI, WEIPING; FAN, ZHILU

    2015-01-01

    The aim of the present study was to investigate the mucus secretion status of mature goblet cells following the application of mitomycin-C (MMC) in ileal neobladder rat models. Bladder substitution models were established in Sprague Dawley rats, which had been divided into five groups, namely the control (sham), normal saline (NS), high-dose MMC (HMMC), low-dose MMC (LMMC) and dehydrated alcohol (DA) groups. To evaluate the total protein concentration and level of sialic acid following the therapy, urine from the rats in each group was collected on days 8, 11 and 14. In addition, to observe the variances between mucus secretion and the ileum goblet cells, immunohistochemistry and hematoxylin and eosin staining were conducted in the different groups on day 17. The results indicated that the ileal neobladder mucosas in the MMC groups were clearly undamaged, as compared with the DA group. Furthermore, the MMC and DA groups were shown to inhibit the proliferation of goblet cells. The concentration of protein and sialic acid in the LMMC group was found to be lower compared with the NS group, while the concentration in the HMMC group was considerably lower. In conclusion, HMMC was demonstrated to evidently reduce the mucin and sialic acid concentration in the urine, without visible damage to the ileal neobladder mucus membrane. Therefore, MMC may provide a novel therapeutic approach for the treatment of certain bladder conditions. PMID:26622360

  19. A case of advanced rectal cancer with rectovesical and ileal fistulae that developed hyperammonemic encephalopathy.

    PubMed

    Maruyama, Masahiro; Miyasaka, Yoshiaki; Takano, Atsushi; Inoue, Masayuki; Furuya, Kazushige; Sugai, Hidemitsu; Hada, Masao; Nakagomi, Hiroshi

    2015-12-01

    Hyperammonemic encephalopathy is rarely caused by a urinary diversion. We herein experienced a case of rectal carcinoma with rectovesical and ileal fistulae that developed hyperammonemic encephalopathy. A 72-year-old man suffered from a fever, diarrhea, pneumaturia, and fecaluria beginning in April 2013 and was referred to our hospital in May 2013. He developed a loss of consciousness and whole body cramping on the first hospital day. The laboratory data indicated an inflammatory reaction and hyperammonemia with a highly elevated serum ammonia (NH3) level of 703 μg/dl. The patient was diagnosed to have rectal carcinoma with rectovesical and ileal fistulae according to computed tomography (CT) and a water-soluble contrast enema. We administered a solution of branched chain amino acids (BCAA) and antibiotics. Furthermore, we repeatedly irrigated bladder through the urethral catheter. The patient's symptoms recovered, and the serum ammonia levels on the second and third hospital day were decreased to 210 and 135 μg/dl, respectively. However, the symptoms of infection and confusion were suspected to repeat; we elected to perform surgical treatment. An ileal disconnection with ileocecal bypass and sigmoidostomy were effective for preventing hyperammonemic encephalopathy. PMID:26435908

  20. Role of glutathione, glutathione transferase, and glutaredoxin in regulation of redox-dependent processes.

    PubMed

    Kalinina, E V; Chernov, N N; Novichkova, M D

    2014-12-01

    Over the last decade fundamentally new features have been revealed for the participation of glutathione and glutathione-dependent enzymes (glutathione transferase and glutaredoxin) in cell proliferation, apoptosis, protein folding, and cell signaling. Reduced glutathione (GSH) plays an important role in maintaining cellular redox status by participating in thiol-disulfide exchange, which regulates a number of cell functions including gene expression and the activity of individual enzymes and enzyme systems. Maintaining optimum GSH/GSSG ratio is essential to cell viability. Decrease in the ratio can serve as an indicator of damage to the cell redox status and of changes in redox-dependent gene regulation. Disturbance of intracellular GSH balance is observed in a number of pathologies including cancer. Consequences of inappropriate GSH/GSSG ratio include significant changes in the mechanism of cellular redox-dependent signaling controlled both nonenzymatically and enzymatically with the participation of isoforms of glutathione transferase and glutaredoxin. This review summarizes recent data on the role of glutathione, glutathione transferase, and glutaredoxin in the regulation of cellular redox-dependent processes. PMID:25749165

  1. Strategies of mucosal immunotherapy for allergic diseases

    PubMed Central

    Ye, Yi-Ling; Chuang, Ya-Hui; Chiang, Bor-Luen

    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 and lower side-effect profile. This study reviews recent progress in mucosal immunotherapy for allergic diseases. Administration routes, antigen quality and quantity, and adjuvants used are major considerations in this field. Also, direct uses of unique probiotics, or specific cytokines, have been discussed. Furthermore, some researchers have reported new therapeutic ideas that combine two or more strategies. The most important strategy for development of mucosal therapies for allergic diseases is the improvement of antigen formulation, which includes continuous searching for efficient adjuvants, collecting more information about dominant T-cell epitopes of allergens, and having the proper combination of each. In clinics, when compared to other mucosal routes, sublingual immunotherapy (SLIT) is a preferred choice for therapeutic administration, although local and systemic side effects have been reported. Additionally, not every allergen has the same beneficial effect. Further studies are needed to determine the benefits of mucosal immunotherapy for different allergic diseases after comparison of the different administration routes in children and adults. Data collected from large, well-designed, double-blind, placebo-controlled, and randomized trials, with post-treatment follow-up, can provide robust substantiation of current evidence. PMID:21666705

  2. Strategies of mucosal immunotherapy for allergic diseases.

    PubMed

    Ye, Yi-Ling; Chuang, Ya-Hui; Chiang, Bor-Luen

    2011-11-01

    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 and lower side-effect profile. This study reviews recent progress in mucosal immunotherapy for allergic diseases. Administration routes, antigen quality and quantity, and adjuvants used are major considerations in this field. Also, direct uses of unique probiotics, or specific cytokines, have been discussed. Furthermore, some researchers have reported new therapeutic ideas that combine two or more strategies. The most important strategy for development of mucosal therapies for allergic diseases is the improvement of antigen formulation, which includes continuous searching for efficient adjuvants, collecting more information about dominant T-cell epitopes of allergens, and having the proper combination of each. In clinics, when compared to other mucosal routes, sublingual immunotherapy (SLIT) is a preferred choice for therapeutic administration, although local and systemic side effects have been reported. Additionally, not every allergen has the same beneficial effect. Further studies are needed to determine the benefits of mucosal immunotherapy for different allergic diseases after comparison of the different administration routes in children and adults. Data collected from large, well-designed, double-blind, placebo-controlled, and randomized trials, with post-treatment follow-up, can provide robust substantiation of current evidence. PMID:21666705

  3. Efflux of glutathione and glutathione complexes from human erythrocytes in response to vanadate.

    PubMed

    Cakir, Yeliz; Yildiz, Deniz

    2013-01-01

    The main objective of the present study was to investigate if vanadate is extruded from the cells in a glutathione dependent manner resulting in the appearance of extracellular glutathione and complexes of glutathione with vanadium. Vanadate significantly depleted intracellular non-protein sulfhydryl (NPSH) levels in a time- and concentration-dependent manner. The intracellular NPSH level was decreased to 0.0 0.0 ?mol/ml erythrocyte when exposed to 10 mM of vanadate for 4h. Extracellular NPSH level was increased concomitantly with the intracellular decrease and reached to 0.1410 0.005 ?mol/ml erythrocyte in 4h. Intracellular decrease and extracellular increase in NPSH levels were significantly inhibited in the presence of DIDS, a chloride-bicarbonate exchanger which also mediates phosphate and arsenate transport in erythrocytes. In parallel with the increase in extracellular NPSH levels, significant increases in extracellular glutathione levels were detected following exposure to vanadate. Extracellular glutathione levels reached to 0.0150 0.0.001, 0.0330 0.001, and 0.0576 0.002 ?mol/ml erythrocyte with 1, 5, and 10 mM of vanadate respectively. Dimercaptosuccinic acid treatment of supernatants significantly increased the glutathione levels measured in the extracellular media. Utilization of MK571 an MRP inhibitor decreased the rate of glutathione efflux from erythrocytes suggesting a role for this membrane transporter in the process. A known methylation inhibitor periodate oxidized adenosine decreased the rate of glutathione efflux from erythrocytes. This observed decrease in extracellular GSH levels suggests that GSH release partly requires a proper cellular methylation process and that part of GSH detected in the extracellular media may arise from GSH-vandium complexes. The results of the present study indicate that human erythrocyte efflux glutathione in reduced free form and in conjugated form/s that can be recovered with dimercaptosuccinic acid when exposed to vanadate. PMID:22824382

  4. 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.

  5. A clinical trial of glutathione supplementation in autism spectrum disorders

    PubMed Central

    Kern, Janet K.; Geier, David A.; Adams, James B.; Garver, Carolyn R.; Audhya, Tapan; Geier, Mark R.

    2011-01-01

    Summary Background Recent evidence shows that subjects diagnosed with an autism spectrum disorder (ASD) have significantly lower levels of glutathione than typically developing children. The purpose of this study was to examine the use of two commonly used glutathione supplements in subjects diagnosed with an ASD to determine their efficacy in increasing blood glutathione levels in subjects diagnosed with an ASD. Material/Methods The study was an eight-week, open-label trial using oral lipoceutical glutathione (n=13) or transdermal glutathione (n=13) in children, 3–13 years of age, with a diagnosis of an ASD. Subjects underwent pre- and post-treatment lab testing to evaluate plasma reduced glutathione, oxidized glutathione, cysteine, taurine, free and total sulfate, and whole-blood glutathione levels. Results The oral treatment group showed significant increases in plasma reduced glutathione, but not whole-blood glutathione levels following supplementation. Both the oral and transdermal treatment groups showed significant increases in plasma sulfate, cysteine, and taurine following supplementation. Conclusions The results suggest that oral and transdermal glutathione supplementation may have some benefit in improving some of the transsulfuration metabolites. Future studies among subjects diagnosed with an ASD should further explore the pharmacokinetics of glutathione supplementation and evaluate the potential effects of glutathione supplementation upon clinical symptoms. PMID:22129897

  6. Five decades with glutathione and the GSTome.

    PubMed

    Mannervik, Bengt

    2012-02-24

    Uncle Folke inspired me to become a biochemist by demonstrating electrophoresis experiments on butterfly hemolymph in his kitchen. Glutathione became the subject for my undergraduate project in 1964 and has remained a focal point in my research owing to its multifarious roles in the cell. Since the 1960s, the multiple forms of glutathione transferase (GST), the GSTome, were isolated and characterized, some of which were discovered in our laboratory. Products of oxidative processes were found to be natural GST substrates. Examples of toxic compounds against which particular GSTs provide protection include 4-hydroxynonenal and ortho-quinones, with possible links to the etiology of Alzheimer and Parkinson diseases and other degenerative conditions. The role of thioltransferase and glutathione reductase in the cellular reduction of disulfides and other oxidized forms of thiols was clarified. Glyoxalase I catalyzes still another glutathione-dependent detoxication reaction. The unusual steady-state kinetics of this zinc-containing enzyme initiated model discrimination by regression analysis. Functional properties of the enzymes have been altered by stochastic mutations based on DNA shuffling and rationally tailored by structure-based redesign. We found it useful to represent promiscuous enzymes by vectors or points in multidimensional substrate-activity space and visualize them by multivariate analysis. Adopting the concept "molecular quasi-species," we describe clusters of functionally related enzyme variants that may emerge in natural as well as directed evolution. PMID:22247548

  7. Five Decades with Glutathione and the GSTome

    PubMed Central

    Mannervik, Bengt

    2012-01-01

    Uncle Folke inspired me to become a biochemist by demonstrating electrophoresis experiments on butterfly hemolymph in his kitchen. Glutathione became the subject for my undergraduate project in 1964 and has remained a focal point in my research owing to its multifarious roles in the cell. Since the 1960s, the multiple forms of glutathione transferase (GST), the GSTome, were isolated and characterized, some of which were discovered in our laboratory. Products of oxidative processes were found to be natural GST substrates. Examples of toxic compounds against which particular GSTs provide protection include 4-hydroxynonenal and ortho-quinones, with possible links to the etiology of Alzheimer and Parkinson diseases and other degenerative conditions. The role of thioltransferase and glutathione reductase in the cellular reduction of disulfides and other oxidized forms of thiols was clarified. Glyoxalase I catalyzes still another glutathione-dependent detoxication reaction. The unusual steady-state kinetics of this zinc-containing enzyme initiated model discrimination by regression analysis. Functional properties of the enzymes have been altered by stochastic mutations based on DNA shuffling and rationally tailored by structure-based redesign. We found it useful to represent promiscuous enzymes by vectors or points in multidimensional substrate-activity space and visualize them by multivariate analysis. Adopting the concept “molecular quasi-species,” we describe clusters of functionally related enzyme variants that may emerge in natural as well as directed evolution. PMID:22247548

  8. Mucosal Adjuvanticity and Immunogenicity of LTR72, a Novel Mutant of Escherichia coli Heat-labile Enterotoxin with Partial Knockout of ADP-ribosyltransferase Activity

    PubMed Central

    Giuliani, Marzia Monica; Del Giudice, Giuseppe; Giannelli, Valentina; Dougan, Gordon; Douce, Gill; Rappuoli, Rino; Pizza, Mariagrazia

    1998-01-01

    Heat-labile Escherichia coli enterotoxin (LT) has the innate property of being a strong mucosal immunogen and adjuvant. In the attempt to reduce toxicity and maintain the useful immunological properties, several LT mutants have been produced. Some of these are promising mucosal adjuvants. However, so far, only those that were still toxic maintained full adjuvanticity. In this paper we describe a novel LT mutant with greatly reduced toxicity that maintains most of the adjuvanticity. The new mutant (LTR72), that contains a substitution Ala → Arg in position 72 of the A subunit, showed only 0.6% of the LT enzymatic activity, was 100,000-fold less toxic than wild-type LT in Y1 cells in vitro, and was at least 20 times less effective than wild-type LT in the rabbit ileal loop assay in vivo. At a dose of 1 μg, LTR72 exhibited a mucosal adjuvanticity, similar to that observed with wild-type LT, better than that induced by the nontoxic, enzymatically inactive LTK63 mutant, and much greater than that of the recombinant B subunit. This trend was consistent for both the amounts and kinetics of the antibody induced, and priming of antigen-specific T lymphocytes. The data suggest that the innate high adjuvanticity of LT derives from the independent contribution of the nontoxic AB complex and the enzymatic activity. LTR72 optimizes the use of both properties: the enzymatic activity for which traces are enough, and the nontoxic AB complex, the effect of which is dose dependent. In fact, in dose–response experiments in mice, 20 μg of LTR72 were a stronger mucosal adjuvant than wild-type LT. This suggests that LTR72 may be an excellent candidate to be tested in clinical trials. PMID:9529328

  9. Efflux of glutathione and glutathione complexes from human erythrocytes in response to inorganic arsenic exposure.

    PubMed

    Yildiz, Deniz; Cakir, Yeliz

    2012-12-01

    The objective of the present study was to investigate if arsenic exposure results in glutathione efflux from human erythrocytes. Arsenite significantly depleted intracellular nonprotein thiol level in a time- and concentration-dependent manner. The intracellular nonprotein thiol level was decreased to 0.767??0.0017?mol/ml erythrocyte following exposure to 10mM of arsenite for 4h. Extracellular nonprotein thiol level was increased concomitantly with the intracellular decrease and reached to 0.481??0.0005?mol/ml erythrocyte in 4h. In parallel with the change in extracellular nonprotein thiol levels, significant increases in extracellular glutathione levels were detected. Extracellular glutathione levels reached to 0.122??0.0013, 0.226??0.003, and 0.274??0.004?mol/ml erythrocyte with 1, 5, and 10mM of arsenite, respectively. Dimercaptosuccinic acid treatment of supernatants significantly increased the glutathione levels measured in the extracellular media. Utilization of MK571 and verapamil, multidrug resistance-associated protein 1 and Pgp inhibitors, decreased the rate of glutathione efflux from erythrocytes suggesting a role for these membrane transporters in the process. The results of the present study indicate that human erythrocytes efflux glutathione in reduced free form and in conjugated form or forms that can be recovered with dimercaptosuccinic acid when exposed to arsenite. PMID:22890881

  10. Protein glycosylation in bacterial mucosal pathogens.

    PubMed

    Szymanski, Christine M; Wren, Brendan W

    2005-03-01

    In eukaryotes, glycosylated proteins are ubiquitous components of extracellular matrices and cellular surfaces. Their oligosaccharide moieties are implicated in a wide range of cell-cell and cell-matrix recognition events that are required for biological processes ranging from immune recognition to cancer development. Glycosylation was previously considered to be restricted to eukaryotes; however, through advances in analytical methods and genome sequencing, there have been increasing reports of both O-linked and N-linked protein glycosylation pathways in bacteria, particularly amongst mucosal-associated pathogens. Studying glycosylation in relatively less-complicated bacterial systems provides the opportunity to elucidate and exploit glycoprotein biosynthetic pathways. We will review the genetic organization, glycan structures and function of glycosylation systems in mucosal bacterial pathogens, and speculate on how this knowledge may help us to understand glycosylation processes in more complex eukaryotic systems and how it can be used for glycoengineering. PMID:15738950

  11. Mucosal melanoma: pathogenesis, clinical behavior, and management.

    PubMed

    Postow, Michael A; Hamid, Omid; Carvajal, Richard D

    2012-10-01

    Mucosal melanoma represents a rare subtype of melanoma with distinct biological, clinical, and management considerations. Knowledge regarding optimal treatment strategies for mucosal melanoma is limited and based primarily upon small case series and single-institution, retrospective analyses. Surgery remains the standard of care for loco-regional management, but the common presence of multifocal disease and the high rate of distant recurrence should be considered before pursuing aggressive surgical interventions associated with inherent significant morbidity. The role of sentinel lymph node biopsy and lymph node dissection remains unclear. Radiotherapy has not been shown to improve overall survival but may reduce the rate of local recurrence. Significant advances in the treatment of metastatic disease have been made with novel immunotherapeutic agents, the discovery of KIT and BRAF mutations and the development of targeted agents that inhibit these oncogenic pathways. PMID:22661391

  12. Duodenal mucosal injury with nonsteroidal antiinflammatory drugs.

    PubMed

    Eliakim, R; Ophir, M; Rachmilewitz, D

    1987-08-01

    The effect of nonsteroidal antiinflammatory drugs (NSAIDs) on duodenal mucosa was assessed both retrospectively and prospectively. In 444 patients with duodenal ulcer, the incidence of upper gastrointestinal bleeding was five times higher in 56 patients who were treated with NSAIDs than in those who did not receive NSAIDs. Indomethacin and naproxen had the most potent damaging effects. In a control group of patients with gastric ulcer, nine out of 134 had taken NSAIDs. The incidence of bleeding in these patients was three times higher than in those who were not on NSAIDs. The effect of indomethacin, 150 mg/day, on the upper gastrointestinal tract was examined in a prospective study of 75 patients with acute musculoskeletal disorders. Endoscopy after 1 week of therapy showed that 45% had mucosal damage in the duodenum, and this was as frequent and as severe as the gastric mucosal damage. In most instances, the duodenal damage was erosive duodenitis. PMID:3498747

  13. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Glutathione reductase assay. 864.7375 Section 864...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7375 Glutathione reductase assay. (a) Identification. A glutathione reductase assay is a device used to determine...

  14. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Glutathione reductase assay. 864.7375 Section 864...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7375 Glutathione reductase assay. (a) Identification. A glutathione reductase assay is a device used to determine...

  15. The microbiome and regulation of mucosal immunity

    PubMed Central

    McDermott, Andrew J; Huffnagle, Gary B

    2014-01-01

    The gastrointestinal tract is a mucosal surface constantly exposed to foreign antigens and microbes, and is protected by a vast array of immunologically active structures and cells. Epithelial cells directly participate in immunological surveillance and direction of host responses in the gut and can express numerous pattern recognition receptors, including Toll-like receptor 5 (TLR5), TLR1, TLR2, TLR3, TLR9, and nucleotide oligomerization domain 2, as well as produce chemotactic factors for both myeloid and lymphoid cells following inflammatory stimulation. Within the epithelium and in the underlying lamina propria resides a population of innate lymphoid cells that, following stimulation, can become activated and produce effector cytokines and exert both protective and pathogenic roles during inflammation. Lamina propria dendritic cells play a large role in determining whether the response to a particular antigen will be inflammatory or anti-inflammatory. It is becoming clear that the composition and metabolic activity of the intestinal microbiome, as a whole community, exerts a profound influence on mucosal immune regulation. The microbiome produces short-chain fatty acids, polysaccharide A, ?-galactosylceramide and tryptophan metabolites, which can induce interleukin-22, Reg3?, IgA and interleukin-17 responses. However, much of what is known about microbiomehost immune interactions has come from the study of single bacterial members of the gastrointestinal microbiome and their impact on intestinal mucosal immunity. Additionally, evidence continues to accumulate that alterations of the intestinal microbiome can impact not only gastrointestinal immunity but also immune regulation at distal mucosal sites. PMID:24329495

  16. 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 228, 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 389, 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

  17. Distribution of macrophages and granulocytes expressing L1 protein (calprotectin) in human Peyer's patches compared with normal ileal lamina propria and mesenteric lymph nodes.

    PubMed Central

    Bjerke, K; Halstensen, T S; Jahnsen, F; Pulford, K; Brandtzaeg, P

    1993-01-01

    Antibodies to the cytosolic leucocyte L1 protein (or calprotectin) were examined for reactivity with macrophages, neutrophils, and eosinophils identified by paired immunofluorescence staining in sections of normal human ileal mucosa, including Peyer's patches. Macrophages were recognised by expression of the myelomonocytic antigen CD68 (monoclonal antibody KP1). Neutrophilic granulocytes were identified by their content of neutrophil elastase, and eosinophilic granulocytes by monoclonal antibody EG2. Virtually all CD68+ macrophages in normal lamina propria and Peyer's patches were L1- and the same was true for most extravasated macrophages in normal peripheral lymph nodes. Some mesenteric lymph nodes, however, and all peripheral lymph nodes with overt pathological processes (malignant lymphoma) contained many CD68+L1+ macrophages. Numerous L1+ cells were also localised to the crypt region and to some extent beneath the villous epithelium in normal lamina propria, but they were mainly identified as EG2+ eosinophils. Such cells were remarkably scarce or absent beneath the follicle associated epithelium in the dome region of Peyer's patches, where CD68+L1- macrophages were abundant. Also subepithelial and interfollicular CD68- interdigitating dendritic cells in Peyer's patches (recognised by antibody to S-100 protein) were usually unreactive with L1 antibody. The L1 protein shows a broad spectrum of antimicrobial activities in vitro, and its putative antiproliferative properties are interesting in relation to the immunosuppression postulated to take place in lamina propria. The virtual absence of L1 producing cells beneath the follicle associated epithelium in Peyer's patches may support the immunostimulatory function of these macrophage rich structures, which are held to be crucial for induction of specific mucosal immunity. Images Figure 1 Figure 2 Figure 3 PMID:8244101

  18. 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

  19. CpG oligodeoxynucleotides as mucosal adjuvants

    PubMed Central

    Iho, Sumiko; Maeyama, Jun-ichi; Suzuki, Fumiko

    2015-01-01

    Bacterial DNA comprising palindromic sequences and containing unmethylated CpG is recognized by toll-like receptor 9 of plasmacytoid dendritic cells (pDCs) and induces the production of interferon-α and chemokines, leading to the activation of a Th1 immune response. Therefore, synthetic equivalents of bacterial DNA (CpG oligodeoxynucleotides) have been developed for clinical applications. They are usually phosphorothioated for in vivo use; this approach also leads to adverse effects as reported in mouse models.Mucosal vaccines that induce both mucosal and systemic immunity received substantial attention in recent years. For their development, phosphodiester-linked oligodeoxynucleotides, including the sequence of a palindromic CpG DNA may be advantageous as adjuvants because their target pDCs are present right there, in the mucosa of the vaccination site. In addition, the probability of adverse effects is believed to be low. Here, we review the discovery of such CpG oligodeoxynucleotides and their possible use as mucosal adjuvants. PMID:25751765

  20. Oral mucosal manifestations of autoimmune skin diseases.

    PubMed

    Mustafa, Mayson B; Porter, Stephen R; Smoller, Bruce R; Sitaru, Cassian

    2015-10-01

    A group of autoimmune diseases is characterised by autoantibodies against epithelial adhesion structures and/or tissue-tropic lymphocytes driving inflammatory processes resulting in specific pathology at the mucosal surfaces and the skin. The most frequent site of mucosal involvement in autoimmune diseases is the oral cavity. Broadly, these diseases include conditions affecting the cell-cell adhesion causing intra-epithelial blistering and those where autoantibodies or infiltration lymphocytes cause a loss of cell-matrix adhesion or interface inflammation. Clinically, patients present with blistering, erosions and ulcers that may affect the skin as well as further mucosal surfaces of the eyes, nose and genitalia. While the autoimmune disease may be suspected based on clinical manifestations, demonstration of tissue-bound and circulating autoantibodies, or lymphocytic infiltrates, by various methods including histological examination, direct and indirect immunofluorescence microscopy, immunoblotting and quantitative immunoassay is a prerequisite for definitive diagnosis. Given the frequency of oral involvement and the fact that oral mucosa is the initially affected site in many cases, the informed practitioner should be well acquainted with diagnostic and therapeutic aspects of autoimmune dermatosis with oral involvement. This paper reviews the pathogenesis and clinical presentation of these conditions in the oral cavity with a specific emphasis on their differential diagnosis and current management approaches. PMID:26117595

  1. Artificial nutrition and intestinal mucosal barrier functionality.

    PubMed

    Anastasilakis, Chrysostomos D; Ioannidis, Orestis; Gkiomisi, Athina I; Botsios, Dimitrios

    2013-01-01

    The gastrointestinal tract has a major role in digestion and absorption of nutrients while playing a leading role in defense of the body. It forms a shield against the invasion of various microorganisms or their products (e.g. antigens, toxins) and therefore it is important to establish its integrity and functionality. That depends on the route of administration and the composition of the artificial nutrition. This study concentrates on the influences of different kinds of artificial nutrition in the functionality of the intestinal mucosal barriers. It seems that full macromolecular solutions of enteral nutrition ensure an adequate mucous immune response, while a lack of nutritional stimulus in the lumen leads rapidly to a dysfunction of gastric-associated lymphatic tissue and mucosal immune system. This dysfunction renders the patients susceptible to infections in distant organs, hospital pneumonia, and multiorgan failure of non-infectious etiology. In patients with indication of total parenteral nutrition administration, addition of bombesin or glutamine preserves mucosal immune response and may limit the adverse effects. PMID:24247113

  2. Leukocyte–Epithelial Interactions and Mucosal Homeostasis

    PubMed Central

    Matthews, Jason D.; Weight, Caroline M.; Parkos, Charles A.

    2015-01-01

    Many common inflammatory disorders are characterized by the infiltration of neutrophils across epithelial lined (mucosal) surfaces resulting in disruption of critical barrier function that protects from microbes and noxious agents. In such conditions, disease symptoms are complex but directly related to leukocyte effects on the barrier and epithelial cell function. It is now highly regarded that cellular factors such as cytokines and receptor–ligand interactions mediating adhesion of leukocytes to epithelial cells have potent effects on epithelial homeostasis, defined by coordinated proliferation, migration, differentiation, and regulated cell shedding. Certain cytokines, for example, not only alter leukocyte interactions with epithelia through changes in expression of adhesion molecules but also affect barrier function through alterations in the composition and dynamics of intercellular junctions. In particular, inflammation-induced loss of many tight junction molecules, in part, can account for dysregulated cellular proliferation, migration, survival, and barrier function. This review will highlight how neutrophils interact with epithelial cells with particular focus on adhesion molecules involved and signaling events that play roles in regulating mucosal homeostasis and pathobiology. A better understanding of these molecular events may provide new ideas for therapeutics directed at attenuating consequences of pathologic inflammation of mucosal surfaces. PMID:24285670

  3. Generation and maintenance of mucosal memory B cell responses?

    PubMed

    Vajdy, M

    2006-01-01

    The mucosal immune system comprises B cells that can mount potent antibody responses against a variety of mucosal pathogens. Mucosal B cell responses can play a decisive role in protection against mucosal pathogens. Induction of mucosal B cell responses can be achieved through mucosal vaccination. However, mucosal administration of antigens without the use of adjuvants or delivery systems can lead to tolerance rather than immunity, and thus considerable efforts have been focused on development of effective immunopotentiating adjuvants and delivery systems. However, because the ultimate goal of vaccination is the induction and maintenance of immunological memory, the underlying mechanisms for induction of long-term mucosal B cell memory need to be analyzed for the selection of appropriate adjuvants. Moreover, as the antigen unspecific innate immune system invoked by adjuvants contributes significantly to the development of antigen-specific B cell responses, and presumably B cell memory, optimal interaction of B cells with cellular components of the innate immune system is required. To better understand the mechanisms that lead to the induction of mucosal antibody responses, antibodies against single epitopes from specific B cell clones as opposed to antibodies against large poly proteins from multiple B cell clones can be studied. This review deals with the concept of mucosal B cell memory with special emphasis on efforts to devise effective prophylactic or therapeutic vaccines. PMID:17073644

  4. Challenges in mucosal vaccines for the control of infectious diseases.

    PubMed

    Azegami, Tatsuhiko; Yuki, Yoshikazu; Kiyono, Hiroshi

    2014-09-01

    The mucosal surface is the largest route through which pathogens enter the human body. To control the outbreak of mucosal infectious diseases, we must use our knowledge of the mucosal immune system to create vaccines that elicit protective mucosal and systemic immunity. Mucosal vaccines have advantages over traditional injectable vaccines in that they not only induce effective mucosal immune responses, but they also do not cause physical or psychological discomfort. Mucosal vaccines currently licensed for human use include oral vaccines against Vibrio cholerae, Salmonella typhi, poliovirus and rotavirus, and nasal vaccines against influenza virus. To further improve the existing vaccines, it will be necessary to develop novel vaccine production, storage and delivery systems through innovative strategies derived from interdisciplinary scientific research. Our accumulated knowledge of the innate and acquired arms of the mucosal immune system and the recent scientific and technical advancements in the fields of molecular biology, plant biology, bio-engineering and chemical engineering, genome biology and systems biology have created a unique research and development platform for the development of the next generation of mucosal vaccines. This review summarizes the current perspectives and future directions of mucosal vaccine development with emphasis on oral and nasal vaccines for the control of infectious diseases. PMID:24914172

  5. Chitosan-based mucosal adjuvants: Sunrise on the ocean.

    PubMed

    Xia, Yufei; Fan, Qingze; Hao, Dongxia; Wu, Jie; Ma, Guanghui; Su, Zhiguo

    2015-11-01

    Mucosal vaccination, which is shown to elicit systemic and mucosal immune responses, serves as a non-invasive and convenient alternative to parenteral administration, with stronger capability in combatting diseases at the site of entry. The exploration of potent mucosal adjuvants is emerging as a significant area, based on the continued necessity to amplify the immune responses to a wide array of antigens that are poorly immunogenic at the mucosal sites. As one of the inspirations from the ocean, chitosan-based mucosal adjuvants have been developed with unique advantages, such as, ability of mucosal adhesion, distinct trait of opening the junctions to allow the paracellular transport of antigen, good tolerability and biocompatibility, which guaranteed the great potential in capitalizing on their application in human clinical trials. In this review, the state of art of chitosan and its derivatives as mucosal adjuvants, including thermo-sensitive chitosan system as mucosal adjuvant that were newly developed by author's group, was described, as well as the clinical application perspective. After a brief introduction of mucosal adjuvants, chitosan and its derivatives as robust immune potentiator were discussed in detail and depth, in regard to the metabolism, safety profile, mode of actions and preclinical and clinical applications, which may shed light on the massive clinical application of chitosan as mucosal adjuvant. PMID:26271831

  6. New perspectives in mucosal immunity with emphasis on vaccine development.

    PubMed

    McGhee, J R; Fujihashi, K; Xu-Amano, J; Jackson, R J; Elson, C O; Beagley, K W; Kiyono, H

    1993-10-01

    In this review, we have purposely focused on five areas that are currently receiving extensive research attention and will be of major importance for development of mucosal and systemic immunity to oral vaccines. These five areas include the following: (1) helper T-cell (Th) subsets and cytokines for mucosal IgA responses; (2) Th1- and Th2-type subsets in regulation of mucosal IgA responses; (3) antigen uptake and presentation in the mucosal immune system; (4) the importance of memory in mucosal immunity to vaccines; and (5) the determination of whether oral immunization alone induces immunity in all mucosal effector tissues. It is now established that the mucosal immune system can be divided into discrete mucosal inductive sites where vaccines/antigens are encountered and taken up, processed, and presented to B and T cells, and separate areas where immune cells actually function (mucosal effector tissues). Further, through the help provided by Th cells and cytokines, the B cells respond to antigen and undergo expansion including memory cell formation. Following the migration of memory B cells to mucosal effector tissues, the cells rapidly develop into IgA plasma cells, and the prevalence of the latter cell type represents a major characteristic of mucosal effector tissues. It also appears that antigen-specific Th cells and perhaps even CD8+ cytotoxic T lymphocytes can make this circular journey (along with memory/activated B cells) from inductive to mucosal effector sites, and this is termed the common mucosal immune system (CMIS). The major implications of the CMIS for development of vaccines would include each of the five components that are discussed. PMID:8303308

  7. 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

  8. Expression of bacterial glutathione reductase in tobacco

    SciTech Connect

    Unger, E.A.; Talbot, D.R. )

    1989-04-01

    Glutathione reductase is the enzyme catalyzing the reduction of oxidized gluthione (GSSG) by NADP. In higher plants glutathione reductase (GR) activity has been associated with several subcellular fractions, but is most notably identified as a chloroplast protein. The enzyme functions in the maintenance of the redox state inside chloroplasts where nearly all of the glutathione present is thought to exist in the reduced form, GSH. Since oxidative stress disturbs the redox status of a chloroplast, GR may play a role in a plant's response to this adversity. We are studying this potential role of GR in transgenic plants. The coding region of the E. coli GR gene was ligated to the coding region of a chloroplast (stromal) transit peptide coding sequence thereby targeting the gene product to the correct subcellular location. This new gene construct was cloned in the Ti plasmid binary vector, pH575, and introduced into the tobacco genome. Expression of this gene product in stress-challenged plants is under investigation.

  9. Mitochondrial Glutathione, a Key Survival Antioxidant

    PubMed Central

    Morales, Albert; Colell, Anna; García-Ruiz, Carmen

    2009-01-01

    Abstract Mitochondria are the primary intracellular site of oxygen consumption and the major source of reactive oxygen species (ROS), most of them originating from the mitochondrial respiratory chain. Among the arsenal of antioxidants and detoxifying enzymes existing in mitochondria, mitochondrial glutathione (mGSH) emerges as the main line of defense for the maintenance of the appropriate mitochondrial redox environment to avoid or repair oxidative modifications leading to mitochondrial dysfunction and cell death. mGSH importance is based not only on its abundance, but also on its versatility to counteract hydrogen peroxide, lipid hydroperoxides, or xenobiotics, mainly as a cofactor of enzymes such as glutathione peroxidase or glutathione-S-transferase (GST). Many death-inducing stimuli interact with mitochondria, causing oxidative stress; in addition, numerous pathologies are characterized by a consistent decrease in mGSH levels, which may sensitize to additional insults. From the evaluation of mGSH influence on different pathologic settings such as hypoxia, ischemia/reperfusion injury, aging, liver diseases, and neurologic disorders, it is becoming evident that it has an important role in the pathophysiology and biomedical strategies aimed to boost mGSH levels. Antioxid. Redox Signal. 11, 2685–2700. PMID:19558212

  10. Obstruction of an ileal urinary conduit in an incarcerated right inguinal hernia.

    PubMed

    Young, M J; Weston, P M T

    2015-04-01

    We present the case of a 72-year-old man with a history of anuria from his ileal conduit 15 months following its formation. That conduit had become incarcerated in a right-sided ingunial hernia. The patient presented with anuria and an acute kidney injury. A clincal diagnosis of an incarcerated hernia was made, and he was taken to theatre for reduction and repair of the hernia. On removal of the conduit from the hernial sac, it began to drain immediately. He made a full recovery, with normalisation of his renal function. PMID:26491738

  11. Radical Cystectomy with Ileal Conduit Urinary Diversion in a Patient with a Left Ventricular Assist Device

    PubMed Central

    Pariser, Joseph J.; Weiner, Adam B.; Steinberg, Gary D.

    2015-01-01

    Left ventricular assist device (LVAD) is an option for the surgical management of severe heart failure, and radical cystectomy remains the standard of care for muscle-invasive bladder cancer. Given a complicated population in terms of comorbidities and management for patients with an LVAD, there is little experience with major urologic procedures, which require balancing the benefits of surgery with considerable perioperative risks. We report our experience performing the first radical cystectomy with ileal conduit in a patient with an LVAD and muscle-invasive bladder cancer. PMID:26290767

  12. [Plasty of extrahepatic biliary ducts with the use of ileal autotransplantate].

    PubMed

    Markov, P V; Onopriev, V I; Fomenko, I V; Grigorov, S P

    2010-01-01

    A method of extrahepatic biliary duct plasty with the use of tubular ileal autotransplantate of 1 sm in diameter was presented in 19 patients with benign strictures. The transplantate on the vascular pedicle was created by resection of the antimesenterial side of the intestinal loop. Distally the anastomosis was performed with the common bile duct, including, thus, papilla Vateri into the bile passage (4 patients). By the impossibility of the latter, the anastomosis was performed with the vertical part of duodenum (16 patients). Postoperative follow-up variated from 1 to 15 years. 18 patients demonstrated good long-term result, 1 patients had a stricture recurrence. PMID:21169941

  13. Ileal tubular duplication; a rare cause of bowel obstruction in adults

    PubMed Central

    Babür, Tuncer

    2016-01-01

    Gastrointestinal tract duplications (GSD) are rare congenital abnormalities. Eighty percent of GSDs are diagnosed in children less than two years of age. These lesions can be seen anywhere from the oral cavity to the anus, but ileum is the most commonly affected site. GSD can be long and tubular, but are usually in the form of cystic masses. The clinical manifestation of GSD in adults is variable, and they are rarely considered as part of differential diagnosis. In this case report, we presented a 20-year-old patient with ileal duplication. Despite medical tests and radiological examinations, the diagnosis could be made during the operation.

  14. Sublingual Delivery of Vaccines for the Induction of Mucosal Immunity

    PubMed Central

    Shim, Byoung-Shik; Choi, Youngjoo; Cheon, In Su

    2013-01-01

    The mucosal surfaces are constantly exposed to incoming pathogens which can cause infections that result in severe morbidity and/or mortality. Studies have reported that mucosal immunity is important for providing protection against these pathogens and that mucosal vaccination is effective in preventing local infections. For many years, the sublingual mucosa has been targeted to deliver immunotherapy to treat allergic hypersensitivities. However, the potential of vaccine delivery via sublingual mucosal has received little attention until recently. Recent studies exploring such potential have documented the safety and effectiveness of sublingual immunization, demonstrating the ability of sublingual immunization to induce both systemic and mucosal immune responses against a variety of antigens, including soluble proteins, inter particulate antigens, and live-attenuated viruses. This review will summarize the recent findings that address the promising potential of sublingual immunization in proving protection against various mucosal pathogens. PMID:23885221

  15. Roles of M cells in infection and mucosal vaccines

    PubMed Central

    Wang, Miao; Gao, Zeqian; Zhang, Zhongwang; Pan, Li; Zhang, Yongguang

    2014-01-01

    The mucosal immune system plays a crucial part in the control of infection. Exposure of humans and animals to potential pathogens generally occurs through mucosal surfaces, thus, strategies that target the mucosa seem rational and efficient vaccination measures. Vaccination through the mucosal immune system can induce effective systemic immune responses simultaneously with mucosal immunity compared with parenteral vaccination. M cells are capable of transporting luminal antigens to the underlying lymphoid tissues and can be exploited by pathogens as an entry portal to invade the host. Therefore, targeting M-cell-specific molecules might enhance antigen entry, initiate the immune response, and induce protection against mucosal pathogens. Here, we outline our understanding of the distribution and function of M cells, and summarize the advances in mucosal vaccine strategies that target M cells. PMID:25483705

  16. Selenium-independent glutathione peroxidase activity associated with glutathione S-transferase from the housefly, Musca domestica.

    PubMed

    Simmons, T W; Jamall, I S; Lockshin, R A

    1989-01-01

    1. A glutathione S-transferase having Se-independent glutathione peroxidase activity was isolated from 100,000 g supernatant from housefly homogenate. 2. The specific activity of the partially purified Se-independent glutathione peroxidase was 1776 nmol NADPH oxidized/min/mg protein, representing an 87-fold purification. 3. The Mr of this enzyme was estimated to be 37,000 and 26,000 by gel filtration chromatography and gel electrophoresis, respectively. 4. Selenium-dependent glutathione peroxidase activity could not be detected in this same supernatant. 5. Se-independent glutathione peroxidase activity should be considered in future studies of the insect antioxidant defense system. PMID:2591193

  17. Formation of styrene glutathione adducts catalyzed by prostaglandin H synthase. A possible new mechanism for the formation of glutathione conjugates

    SciTech Connect

    Stock, B.H.; Bend, J.R.; Eling, T.E.

    1986-05-05

    The metabolism of styrene by prostaglandin hydroperoxidase and horseradish peroxidase was examined. Ram seminal vesicle microsomes in the presence of arachidonic acid or hydrogen peroxide and glutathione converted styrene to glutathione adducts. Neither styrene 7,8-oxide nor styrene glycol was detected as a product in the incubation. Also, the addition of styrene 7,8-oxide and glutathione to ram seminal vesicle microsomes did not yield styrene glutathione adducts. The peroxidase-generated styrene glutathione adducts were isolated by high pressure liquid chromatography and characterized by NMR and tandem mass spectrometry as a mixture of (2R)- and (2S)-S-(2-phenyl-2-hydroxyethyl)glutathione. (1R)- and (1S)-S-(1-phenyl-2-hydroxyethyl)glutathione were not formed by the peroxidase system. The addition of phenol or aminopyrine to incubations, which greatly enhances the oxidation of glutathione to a thiyl radical by peroxidases, increased the formation of styrene glutathione adducts. We propose a new mechanism for the formation of glutathione adducts that is independent of epoxide formation but dependent on the initial oxidation of glutathione to a thiyl radical by the peroxidase, and the subsequent reaction of the thiyl radical with a suitable substrate, such as styrene.

  18. A glutathione reductase mutant of yeast accumulates high levels of oxidized glutathione and requires thioredoxin for growth.

    PubMed Central

    Muller, E G

    1996-01-01

    A glutathione reductase null mutant of Saccharomyces cerevisiae was isolated in a synthetic lethal genetic screen for mutations which confer a requirement for thioredoxin. Yeast mutants that lack glutathione reductase (glr1 delta) accumulate high levels of oxidized glutathione and have a twofold increase in total glutathione. The disulfide form of glutathione increases 200-fold and represents 63% of the total glutathione in a glr1 delta mutant compared with only 6% in wild type. High levels of oxidized glutathione are also observed in a trx1 delta, trx2 delta double mutant (22% of total), in a glr1 delta, trx1 delta double mutant (71% of total), and in a glr1 delta, trx2 delta double mutant (69% of total). Despite the exceptionally high ratio of oxidized/reduced glutathione, the glr1 delta mutant grows with a normal cell cycle. However, either one of the two thioredoxins is essential for growth. Cells lacking both thioredoxins and glutathione reductase are not viable under aerobic conditions and grow poorly anaerobically. In addition, the glr1 delta mutant shows increased sensitivity to the thiol oxidant diamide. The sensitivity to diamide was suppressed by deletion of the TRX2 gene. The genetic analysis of thioredoxin and glutathione reductase in yeast runs counter to previous studies in Escherichia coli and for the first time links thioredoxin with the redox state of glutathione in vivo. Images PMID:8930901

  19. 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

  20. REG3?-deficient mice have altered mucus distribution and increased mucosal inflammatory responses to the microbiota and enteric pathogens in the ileum.

    PubMed

    Loonen, L M P; Stolte, E H; Jaklofsky, M T J; Meijerink, M; Dekker, J; van Baarlen, P; Wells, J M

    2014-07-01

    REG3? is considered to have a protective role against infection with Gram-positive bacteria due to its bactericidal activity, but evidence from in vivo studies is lacking. We generated a REG3?(-/-) mouse, and investigated the effect of lack of REG3? on intestinal mucus distribution, spatial compartmentalization of bacteria, and expression of innate immunity genes. Infection studies were also performed with Gram-positive and Gram-negative pathogens to investigate the antimicrobial role of REG3?. REG3?(-/-) mice display altered mucus distribution, increased bacterial contact with the epithelium, and elevated inflammatory markers in the ileum without histological evidence of pathology. Infection response pathway genes were differentially expressed in both Listeria monocytogenes and Salmonella enteritidis infected REG3?(-/-) and wild-type (wt) mice. Higher amounts of myeloperoxidase and interleukin-22 transcripts were present in the ileal mucosa of REG3?(-/-) than wt mice, but translocation to the organs was unaffected. We concluded that REG3? has a protective role against mucosal infection with pathogenic Listeria and Salmonella in vivo. REG3? is equally distributed throughout the mucus and its absence results in increased epithelial contact with the microbiota resulting in low-grade inflammation. REG3? can bind to Gram-negative and Gram-positive bacteria and influence mucus distribution in the ileum, properties which may contribute to mucosal protection. PMID:24345802

  1. Human milk oligosaccharides shorten rotavirus-induced diarrhea and modulate piglet mucosal immunity and colonic microbiota.

    PubMed

    Li, Min; Monaco, Marcia H; Wang, Mei; Comstock, Sarah S; Kuhlenschmidt, Theresa B; Fahey, George C; Miller, Michael J; Kuhlenschmidt, Mark S; Donovan, Sharon M

    2014-08-01

    The impact of human milk oligosaccharides (HMO) on mucosal immunity, gut microbiota and response to rotavirus (RV) infection was investigated in the piglet model. Newborn piglets were fed with formula alone (FF) or formula supplemented with 4 g l(-1) HMO (HMO) or a prebiotic mixture of 9:1 short-chain galactooligosaccharides (3.6 g l(-1)) and long-chain fructooligosaccharides (0.4 g l(-1)) (PRE) (n=19-21 per group) for 15 days. Piglets (n=7-8) in each dietary group were orally infected with porcine rotavirus (RV) OSU strain on d10, and stool consistency was assessed daily. Blood, small intestine and colonic contents were collected at day 15. Serum RV-specific antibody concentrations, intestinal histomorphology, RV non-structural protein-4 (NSP4) and cytokine mRNA expression were assessed. Colonic content pH, dry matter (DM) and short-chain fatty acid concentrations were measured. Ascending colonic microbiota was analyzed by 16S rRNA gene v1-3 region pyrosequencing. HMO- and PRE-fed groups had shorter duration of diarrhea than FF piglets. Infection changed intestinal histomorphology, increased serum RV-specific antibody response and intestinal RV NSP4 expression, and modulated ileal cytokine expression. HMO enhanced T helper type 1 (interferon-gamma) and anti-inflammatory (interleukin-10) cytokines in the ileum, while prebiotics promoted RV-specific immunoglobulin M response to the infection. RV infection and HMO supplementation altered intraluminal environment and gut microbiota. HMO increased pH and lowered DM of colonic contents and enhanced the abundance of unclassified Lachnospiraceae, which contains numerous butyrate-producing bacteria. In conclusion, HMO and prebiotics did not prevent the onset of RV infection but reduced the duration of RV-induced diarrhea in piglets, in part, by modulating colonic microbiota and immune response to RV infection. PMID:24522264

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

    PubMed

    Lan, Annag; Andriamihaja, Mireille; Blouin, Jean-Marc; Liu, Xinxin; Descatoire, Vronique; Descle de Maredsous, Caroline; Davila, Anne-Marie; Walker, Francine; Tom, Daniel; Blachier, Franois

    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

  3. Multiscale modeling of mucosal immune responses

    PubMed Central

    2015-01-01

    Computational modeling techniques are playing increasingly important roles in advancing a systems-level mechanistic understanding of biological processes. Computer simulations guide and underpin experimental and clinical efforts. This study presents ENteric Immune Simulator (ENISI), a multiscale modeling tool for modeling the mucosal immune responses. ENISI's modeling environment can simulate in silico experiments from molecular signaling pathways to tissue level events such as tissue lesion formation. ENISI's architecture integrates multiple modeling technologies including ABM (agent-based modeling), ODE (ordinary differential equations), SDE (stochastic modeling equations), and PDE (partial differential equations). This paper focuses on the implementation and developmental challenges of ENISI. A multiscale model of mucosal immune responses during colonic inflammation, including CD4+ T cell differentiation and tissue level cell-cell interactions was developed to illustrate the capabilities, power and scope of ENISI MSM. Background Computational techniques are becoming increasingly powerful and modeling tools for biological systems are of greater needs. Biological systems are inherently multiscale, from molecules to tissues and from nano-seconds to a lifespan of several years or decades. ENISI MSM integrates multiple modeling technologies to understand immunological processes from signaling pathways within cells to lesion formation at the tissue level. This paper examines and summarizes the technical details of ENISI, from its initial version to its latest cutting-edge implementation. Implementation Object-oriented programming approach is adopted to develop a suite of tools based on ENISI. Multiple modeling technologies are integrated to visualize tissues, cells as well as proteins; furthermore, performance matching between the scales is addressed. Conclusion We used ENISI MSM for developing predictive multiscale models of the mucosal immune system during gut inflammation. Our modeling predictions dissect the mechanisms by which effector CD4+ T cell responses contribute to tissue damage in the gut mucosa following immune dysregulation. PMID:26329787

  4. 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

  5. Peptic activity and gastroduodenal mucosal damage.

    PubMed Central

    Raufman, J. P.

    1996-01-01

    This contribution reviews briefly the history of the discovery and characterization of peptic activity; secretory models and current concepts regarding the regulation of pepsinogen secretion; and evidence that pepsin is a necessary co-factor for gastroduodenal mucosal injury. Several animal studies indicate that peptic activity is required for acid- and nonsteroidal anti-inflammatory drug-induced gastroduodenal ulceration. A more vigorous approach to the development of anti-peptic drugs for the treatment of peptic ulcer disease is encouraged. Images Figure 1 PMID:9041694

  6. Mucosal Lesions in an Allergy Practice.

    PubMed

    Kohorst, John J; Bruce, Alison J; Torgerson, Rochelle R

    2016-03-01

    The diagnosis and treatment of mucosal disease with an allergic pathogenesis are challenging. Oral allergy is often a hypersensitivity reaction with variable symptoms and physical exam findings. Clinical diagnosis requires a history of prior allergen exposure, a delay from exposure to clinical findings, and improvement following allergen removal. The past decades have seen great contributions to the field of oral allergy. The aim of this review is to provide an approach to the diagnosis and treatment of oral dermatologic disease with a focus on diseases with an investigated allergic pathogenesis. PMID:26922434

  7. The Gut Microbiota and Mucosal T Cells

    PubMed Central

    Smith, Patrick M.; Garrett, Wendy S.

    2011-01-01

    It is intuitive that immune cells in the gut may require microbiota-derived cues for their differentiation. The proximity between host and microbe in the intestine would seemingly necessitate co-adaptation. However, it has been challenging to determine the members and features of the gut microbiota that influence immune system development and function. The recent identification of immunomodulatory members of the commensal microbiota is providing insight into the dependence of select, intestinal immune cell subsets on specific microbial species. In this review, we focus on the gut microbiota's influence on the development and function of mucosal T cells subsets, specifically intraepithelial lymphocytes and lamina propria CD4 T cells. PMID:21833339

  8. Relationships between electromyographic ileal and colonic motility patterns in cats during fasting and feeding.

    PubMed Central

    Cherbut, C; Achard, F; Denavit, M; Roche, M

    1986-01-01

    The relationship between ileal and colonic electromyographic motility patterns were investigated in six awake cats chronically fitted with subserosal electrodes implanted in the smooth muscles of the ileum and colon. Smooth muscle electrical activity (electromyogram) was recorded in both fed and fasted conditions under a 12-12 hours dark-light schedule. It consisted of electrical long spike bursts having two different patterns for each condition. Short sequences of three to five long spike bursts were propagated either aborally or orally from any part of the colon; they were most frequent during the interdigestive or fasting period and no relationship was observed between these long spike bursts and the electrical activity of the ileum. During the digestive or feeding period, the colonic activity was organized in long sequences of 10-15 long spike bursts, termed migrating spike bursts, which started near the caecal junction and propagated aborally to the distal colon. These migrating spike bursts were correlated with the ileal motility. This relationship demonstrated between ileum and colon after feeding is dependent upon the amount of food intake. PMID:3742348

  9. Oral mucosal immunity and HIV infection: current status.

    PubMed

    Challacombe, S J; Sweet, S P

    2002-01-01

    There is a paradox that profound HIV-induced immunodeficiency is present systemically, whereas the majority of infections associated with HIV disease are present or initiated at mucosal surfaces. There is therefore a need to understand both specific and non-specific mechanisms of mucosal protection against HIV and its copathogens. The majority of HIV infections occur as a result of the passage of virus across mucosal membranes. Resistance to HIV infection at mucosal surfaces may be related to HIV-specific CD8+ T cell responses in some individuals and may be the basis for protective vaccine design. However, T-cells, macrophages and dendritic cells in mucosa may be a portal of entry for HIV. Transcytosis of HIV can occur from the mucosal to the submucosal surface and vice versa, and may be inhibited by mucosal immunoglobulins and neutralizing IgA within epithelial cells. HIV-induced alterations to oral epithelial cells, together with impairment of mucosal CD4+ T-cells and consequent altered cytokine secretion, may contribute to secondary infections. It also appears that HIV infection is associated with decreased salivary IgA levels, although a dichotomy between IgA concentrations in saliva and serum has been reported. Mucosal antibody responses, however, seem to be maintained. Considerable attention has been given to the possibility of mucosal immunization against HIV and there is evidence that secretory IgA antibody is neutralizing to different HIV strains. In addition to specific immune factors, it is likely that innate nonspecific factors may be significant in protecting mucosal surfaces, including lactoferrin, secretory leukocyte protease inhibitor, mucins, proline rich proteins and cystatins. These may be useful candidate virucides in topical preparations. Thus humoral, cellular and innate immune mechanisms, as well as lymphocyte-epithelial interactions, may all be impaired at mucosal surfaces as a result of HIV infection and may contribute to the susceptibility of mucosa to infective processes. PMID:12164661

  10. Intestinal epithelial cell regulation of mucosal inflammation.

    PubMed

    Yu, Yimin; Sitaraman, Shanthi; Gewirtz, Andrew T

    2004-01-01

    The intestinal epithelium serves as one of human's primary interfaces with the outside world. This interface is very heavily colonized with bacteria and yet permits absorption of life-sustaining nutrients while protecting the tissues below from microbial onslaught. Although the gut epithelium had been classically thought to achieve this function primarily by functioning as a passive, albeit highly selective, barrier, research over the last decade has demonstrated that in fact the epithelium plays a very active role in protecting the host from the bacteria that colonize it. As a consequence of its mediation of mucosal immunity, intestinal epithelial dysfunction appears to be central to diseases associated with aberrant gut mucosal immune responses such as inflammatory bowel disease (IBD). This article reviews: (1) how the gut epithelium participates in regulating innate immune inflammatory responses to enteric pathogens, (2) how these responses may regulate the adaptive immune system, (3) mechanisms that may resolve acute inflammation, and (4) how epithelial dysfunction may participate in regulating both the active and chronic phases of IBD. PMID:15181270

  11. Mucosal immunity against parasitic gastrointestinal nematodes

    PubMed Central

    Onah, Denis Nnabuike

    2000-01-01

    The last two decades witnessed significant advances in the efforts of immunoparasitologists to elucidate the nature and role of the host mucosal defence mechanisms against intestinal nematode parasites. Aided by recent advances in basic immunology and biotechnology with the concomitant development of well defined laboratory models of infection, immunoparasitologists have more precisely analyzed and defined the different immune effector mechanisms during the infection; resulting in great improvement in our current knowledge and understanding of protective immunity against gastrointestinal (GI) nematode parasites. Much of this current understanding comes from experimental studies in laboratory rodents, which have been used as models of livestock and human GI nematode infections. These rodent studies, which have concentrated on Heligmosomoides polygyrus, Nippostrongylus brasiliensis, Strongyloides ratti/S. venezuelensis, Trichinella spiralis and Trichuris muris infections in mice and rats, have helped in defining the types of T cell responses that regulate effector mechanisms and the effector mechanisms responsible for worm expulsion. In addition, these studies bear indications that traditionally accepted mechanisms of resistance such as eosinophilia and IgE responses may not play as important roles in protection as were previously conceived. In this review, we shall, from these rodent studies, attempt an overview of the mucosal and other effector responses against intestinal nematode parasites beginning with the indices of immune protection as a model of the protective immune responses that may occur in animals and man. PMID:11138315

  12. Canine oral mucosal mast cell tumours.

    PubMed

    Elliott, J W; Cripps, P; Blackwood, L; Berlato, D; Murphy, S; Grant, I A

    2016-03-01

    Mast cell tumours (MCTs) are the most common cutaneous tumours of dogs, however rarely they can arise from the oral mucosa. This subset of MCT is reported to demonstrate a more aggressive clinical course than those tumours on the haired skin and the authors hypothesised that dogs with oral, mucosal MCT would have a high incidence of local lymph node metastasis at presentation and that this would be a negative prognostic factor. An additional hypothesis was that mitotic index (MI) would be prognostic. This retrospective study examines 33 dogs with MCTs arising from the oral mucosa. The results suggest that oral mucosal MCTs in the dog have a high incidence of lymph node metastasis at diagnosis (55%) which results in a poor prognosis. MI and nodal metastasis is highly prognostic. Loco-regional progression is common in these patients and dogs with adequate local control of their tumour had an improved outcome. Despite a more aggressive clinical course, treatment can result in protracted survivals, even when metastasis is present. PMID:24215587

  13. Mucosal Melanoma: Epidemiology, Biology and Treatment.

    PubMed

    Spencer, Kristen R; Mehnert, Janice M

    2016-01-01

    Mucosal melanoma is an exceedingly rare variant of cutaneous melanoma that, due to its rarity, is poorly described and infrequently studied. Primary sites of origin include the head and neck, anorectum and vulvovaginal regions. It is uniquely different from cutaneous melanoma with respect to epidemiology, etiology, pathogenesis and prognosis. The etiology and pathogenesis remain unclear. Unlike cutaneous melanoma, exposure to UV light is not an apparent risk factor. Furthermore, distinct molecular features including a lower incidence of BRAF oncogene mutations but a higher incidence of KIT oncogene mutations suggest divergent genetic etiologies. Mucosal melanomas generally present at a later stage, are more aggressive and carry a worse prognosis regardless of the stage at diagnosis. Establishing standardized treatment guidelines has been challenging due to the rarity of the disease. Early detection provides the best chance at survival but is often difficult due to anatomic location. Surgery remains the primary therapeutic intervention if complete resection is technically feasible given the anatomic location. Radiotherapy may be used to achieve local control when resection is not feasible, or adjuvantly to enhance locoregional control, but most studies have failed to demonstrate an improvement in overall survival. There are no consensus guidelines on the optimal systemic therapy, and regimens are often extrapolated from data based on therapies used to treat advanced cutaneous melanoma. Clinical trials, particularly utilizing newer targeted therapies and immunotherapies, are investigating novel treatment approaches. PMID:26601869

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

    PubMed

    Elia, Antonia Concetta; Fanetti, Alessia; Drr, 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

  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. 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...

  17. Standardized ileal digestible tryptophan to lysine ratios in growing pigs fed corn-based and non-corn-based diets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two 21-d experiments were conducted to determine the optimum standard ileal digestible (SID) Trp:Lys ratio in growing pigs fed corn-based diets compared to non-corn-based diets. The primary response variables in both experiments were ADG and plasma urea N (PUN) concentrations with the optimum SID Tr...

  18. Breast metastasis as the first clinical manifestation of ileal neuroendocrine tumor. A challenging diagnosis with relevant clinical implications.

    PubMed

    La Rosa, Stefano; Casnedi, Selenia; Maragliano, Roberta; Goyault, Gilles; Weber, Jean-Christophe; Louis, Bernard; Schlund, Elvire; Sessa, Fausto

    2015-05-01

    Ileal neuroendocrine tumors are slow-growing grade 1 or, more rarely, grade 2 neuroendocrine tumors which, however, are frequently metastatic to regional lymph nodes and the liver. A few cases of ileal neuroendocrine tumors that are metastatic to the breast have also been reported in the medical literature. The knowledge of this uncommon clinical presentation is of great importance because it needs to be differentiated from primary breast carcinomas with neuroendocrine features, which represent completely different entities with a different therapeutic approach. The diagnosis of a breast metastasis from an ileal neuroendocrine tumor and its distinction from a well-differentiated primary neuroendocrine tumor of the breast is a challenging task for clinicians and pathologists. This workup is particularly difficult when the breast lesion is the first sign of malignancy. In the present paper, we describe the clinicopathological features of an ileal neuroendocrine tumor first presenting with a breast metastasis in a 50-year-old woman and we discuss the key diagnostic features for the differential diagnosis with primary well-differentiated neuroendocrine tumor of the breast. Moreover, we have reviewed the medical literature to give the reader a comprehensive overview on this topic. PMID:25935445

  19. 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...

  20. 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...

  1. Bacterial interplay at intestinal mucosal surfaces: implications for vaccine development.

    PubMed

    Autenrieth, I B; Schmidt, M A

    2000-10-01

    The discovery of 'molecular syringes' in several important gastrointestinal pathogens including Escherichia coli, Salmonella, Shigella and Yersinia, together with a better understanding of M cells and the mucosal immune system, has advanced our appreciation of multistage microorganism-host cell interactions. Recent studies suggest that these molecular strategies could be adapted for the development of modular mucosal vaccines. PMID:11044680

  2. 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

  3. Effects of mucosal loading on vocal fold vibration

    NASA Astrophysics Data System (ADS)

    Tao, Chao; Jiang, Jack J.

    2009-06-01

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

  4. 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...

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

    PubMed Central

    Sarrin-Prez, 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

  6. Mucosal Correlates of Protection in HIV-1-Exposed Seronegative Persons

    PubMed Central

    Shen, Ruizhong; Smith, Phillip D.

    2014-01-01

    Resistance to HIV-1 infection in HIV-1-exposed seronegative (HESN) persons offers a promising opportunity to identify mechanisms of “natural” protection. Unique features of the mucosa in particular may contribute to this protection. Here we highlight several key issues pertaining to the mucosal correlates of protection in HESN persons, including humoral immune responses, mechanisms of mucosal HIV-1-neutralization, immune cell activation, and role of the microbiota in mucosal responses. We also discuss mucosal model systems that can be used to investigate the mechanisms of resistance in HESN subjects. A clear understanding of the mucosal correlates of protection against HIV-1 in HESN persons will provide critical new insights for the development of effective vaccine and microbicide strategies for the prevention of HIV-1 transmission. PMID:24428610

  7. Regulation of Signal Transduction by Glutathione Transferases

    PubMed Central

    Pajaud, Julie; Kumar, Sandeep; Rauch, Claudine; Morel, Fabrice; Aninat, Caroline

    2012-01-01

    Glutathione transferases (GST) are essentially known as enzymes that catalyse the conjugation of glutathione to various electrophilic compounds such as chemical carcinogens, environmental pollutants, and antitumor agents. However, this protein family is also involved in the metabolism of endogenous compounds which play critical roles in the regulation of signaling pathways. For example, the lipid peroxidation product 4-hydroxynonenal (4-HNE) and the prostaglandin 15-deoxy-?12,14-prostaglandin J2 (15d-PGJ2) are metabolized by GSTs and these compounds are known to influence the activity of transcription factors and protein kinases involved in stress response, proliferation, differentiation, or apoptosis. Furthermore, several studies have demonstrated that GSTs are able to interact with different protein partners such as mitogen activated protein kinases (i.e., c-jun N-terminal kinase (JNK) and apoptosis signal-regulating kinase 1 (ASK1)) which are also involved in cell signaling. New functions of GSTs, including S-glutathionylation of proteins by GSTs and ability to be a nitric oxide (NO) carrier have also been described. Taken together, these observations strongly suggest that GST might play a crucial role during normal or cancer cells proliferation or apoptosis. PMID:23094162

  8. Systematic characterization of porcine ileal Peyer's patch, II. A role for CD154 on T cells in the positive selection of immature porcine ileal Peyer's patch B cells

    PubMed Central

    Andersen, J K; Takamatsu, H; Pullen, L; Parkhouse, R M E

    1999-01-01

    We previously demonstrated that the majority (? 90%) of porcine ileal Peyer's patch (IPP) follicular cells are immature B cells destined to die by apoptosis, when incubated at 37. In this paper we approached the mechanisms responsible for positive selection of porcine IPP follicular immature B?cell selection, by screening for various cell types, cytokines and polyclonal and monoclonal antibodies for promoting the survival of IPP B cells. Of these reagents, only CD3 cross?linked purified T cells from mesenteric lymph nodes were able to rescue IPP follicular B cells from apoptosis, although polyclonal anti?IPP lymphocyte antibodies delayed apoptosis. This survival effect could be reproduced simply by incubating IPP follicular B cells with soluble and cell membrane?expressed CD154, an observation consistent with the demonstrated presence of CD40 and CD154 on porcine IPP follicular B cells and activated T cells, respectively. The IPP follicular B cells rescued in this manner expressed a more mature surface marker phenotype. Immunohistology and fluorescence?activated cell sorter analysis demonstrated that subpopulations of IPP follicular T cells (less than 05%) express CD154. Thus, perhaps unexpectedly, CD154 on T cells may play a role in the positive selection of immature B cells in the porcine IPP. The origin and control of the activated T cells identified within the porcine IPP remains to be investigated. PMID:10594697

  9. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... measure glutathione (the tripeptide of glycine, cysteine, and glutamic acid) in erythrocytes (red blood... hemolytic (erythrocyte destroying) anemias due to an inherited enzyme deficiency. (b) Classification....

  10. Molecular weight distribution of soluble fiber fractions and short chain fatty acids in ileal digesta of growing pigs.

    PubMed

    Ivarsson, E; Andersson, R; Lindberg, J E

    2012-12-01

    The effect of dietary fiber source on molecular weight (MW) distribution of soluble fiber fractions and short chain fatty acids (SCFA) in ileal digesta of 7 post valve T-cecum (PVTC) cannulated growing pigs was studied. Pigs were fed semisynthetic diets with sugar beet (Beta vulgaris) pulp (SBP) or chicory (Cichorium intybus) forage (CFO) as fiber sources of which the soluble nonstarch polysaccharide (NSP) fraction originated mainly from pectin. Three MW intervals were selected-large MW (MWL): 10,000,000 to 1,000,000 g/mol, medium MW (MWM): 1,000,000 to 200,000 g/mol, and small MW (MWS): 200,000 to 10,000 g/mol-and the relative distribution (% of total) of molecules in each interval was calculated. The MWM fraction was higher (P < 0.05) in ileal digesta of pigs fed diet SBP and the MWS fraction was higher (P < 0.05) in ileal digesta of pigs fed diet CFO. The mole/100 mole of propionic acid (HPr) was higher (P < 0.010) in pigs fed diet SBP whereas pigs fed diet CFO had higher (P < 0.010) mole/100 mole of acetic acid (HAc). The proportion of the MWL and MWM fractions in ileal digesta were negatively correlated to HAc (r = -0.52, P = 0.05, and r = -0.62, P = 0.02, respectively). The proportion of MWM in ileal digesta was positively correlated to HPr (r = 0.83; P = 0.001) whereas MWS and HPr were negatively correlated (r = -0.76; P = 0.002). In conclusion, the bacterial degradation of the soluble NSP fraction is selective and MW distribution may explain differences in SCFA production. PMID:23365284

  11. 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-1β and NF-κB 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-κB 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

  12. Autologous Transplantation of Oral Mucosal Epithelial Cell Sheets Cultured on an Amniotic Membrane Substrate for Intraoral Mucosal Defects

    PubMed Central

    Amemiya, Takeshi; Nakamura, Takahiro; Yamamoto, Toshiro; Kinoshita, Shigeru; Kanamura, Narisato

    2015-01-01

    The human amniotic membrane (AM) is a thin intrauterine placental membrane that is highly biocompatible and possesses anti-inflammatory and anti-scarring properties. Using AM, we developed a novel method for cultivating oral mucosal epithelial cell sheets. We investigated the autologous transplantation of oral mucosal epithelial cells cultured on AM in patients undergoing oral surgeries. We obtained specimens of AM from women undergoing cesarean sections. This study included five patients without any history of a medical disorder who underwent autologous cultured oral epithelial transplantation following oral surgical procedures. Using oral mucosal biopsy specimens obtained from these patients, we cultured oral epithelial cells on an AM carrier. We transplanted the resultant cell sheets onto the oral mucosal defects. Patients were followed-up for at least 12 months after transplantation. After 2–3 weeks of being cultured on AM, epithelial cells were well differentiated and had stratified into five to seven layers. Immunohistochemistry revealed that the cultured cells expressed highly specific mucosal epithelial cell markers and basement membrane proteins. After the surgical procedures, no infection, bleeding, rejection, or sheet detachment occurred at the reconstructed sites, at which new oral mucous membranes were evident. No recurrence was observed in the long-term follow-up, and the postoperative course was excellent. Our results suggest that AM-cultured oral mucosal epithelial cell sheets represent a useful biomaterial and feasible method for oral mucosal reconstruction. However, our primary clinical study only evaluated their effects on a limited number of small oral mucosal defects. PMID:25915046

  13. Mucosal immunity to pathogenic intestinal bacteria.

    PubMed

    Perez-Lopez, Araceli; Behnsen, Judith; Nuccio, Sean-Paul; Raffatellu, Manuela

    2016-03-01

    The intestinal mucosa is a particularly dynamic environment in which the host constantly interacts with trillions of commensal microorganisms, known as the microbiota, and periodically interacts with pathogens of diverse nature. In this Review, we discuss how mucosal immunity is controlled in response to enteric bacterial pathogens, with a focus on the species that cause morbidity and mortality in humans. We explain how the microbiota can shape the immune response to pathogenic bacteria, and we detail innate and adaptive immune mechanisms that drive protective immunity against these pathogens. The vast diversity of the microbiota, pathogens and immune responses encountered in the intestines precludes discussion of all of the relevant players in this Review. Instead, we aim to provide a representative overview of how the intestinal immune system responds to pathogenic bacteria. PMID:26898110

  14. Histamine and gut mucosal immune regulation.

    PubMed

    Smolinska, S; Jutel, M; Crameri, R; O'Mahony, L

    2014-03-01

    Histamine is a biogenic amine with extensive effects on many cell types, mediated by the activation of its four receptors (H1R-H4R). Distinct effects are dependent on receptor subtypes and their differential expression. Within the gastrointestinal tract, histamine is present at relatively high concentrations, particularly during inflammatory responses. In this review, we discuss the immunoregulatory influence of histamine on a number of gastrointestinal disorders, including food allergy, scombroid food poisoning, histamine intolerance, irritable bowel syndrome, and inflammatory bowel disease. It is clear that the effects of histamine on mucosal immune homeostasis are dependent on expression and activity of the four currently known histamine receptors; however, the relative protective or pathogenic effects of histamine on inflammatory processes within the gut are still poorly defined and require further investigation. PMID:24286351

  15. Mucosal Immunity and acute viral gastroenteritis.

    PubMed

    Rose, Markus A

    2014-01-01

    Acute gastroenteritis is a major killer of the very young worldwide. Rotavirus is the most common intestinal virus, causing acute gastroenteritis and extra-intestinal complications especially in young and chronically ill subjects. As early as 1991, the WHO recommended as high priority the development of a vaccine against rotavirus, the major pathogen causing enteric infections. Since the introduction of rotavirus vaccines for infant immunization programmes in different parts of the world in 2006, vaccination against rotavirus has resulted in substantial declines in severe gastroenteritis. The oral rotavirus vaccines RotaTeq() and Rotarix() are excellent examples for their unique features and principles of mucosal immunization. We elaborate on rotavirus immunity and the success of rotavirus vaccination and aspects also beyond infants' acute gastroenteritis. PMID:25424826

  16. Mucosal adenovirus-vectored vaccine for measles.

    PubMed

    Lobanova, Liubov M; Baig, Tayyba T; Tikoo, Suresh K; Zakhartchouk, Alexander N

    2010-11-10

    Several problems associated with the available anti-measles vaccine emphasize the need for a single shot anti-measles vaccine which is efficacious by mucosal route of administration and functional in the presence of anti-measles neutralizing antibodies. To achieve these goals, we constructed two recombinant human adenoviruses (collectively designated Ad-F/H) carrying genes for measles virus (MV) fusion (F) and haemagglutinin (H) proteins. Single intranasal or intramuscular vaccination of mice and cotton rats with Ad-F/H elicited high MV-specific serum neutralizing-antibody titers. Furthermore, bronchoalveolar lavage samples from mice vaccinated intranasally with Ad-F/H showed a 100-fold increase in MV-specific IgA titers compared with intramuscularly vaccinated mice. Moreover, Ad-F/H vaccine administered intranasally, but not intramuscularly, completely protected challenged cotton rats from MV replication in the lungs. PMID:20887832

  17. Topical and mucosal liposomes for vaccine delivery.

    PubMed

    Romero, Eder Lilia; Morilla, Maria Jose

    2011-01-01

    Mucosal (and in minor extent transcutanous) stimulation can induce local or distant mucosa secretory IgA. Liposomes and other vesicles as mucosal and transcutaneous adjuvants are attractive alternatives to parenteral vaccination. Liposomes can be massively produced under good manufacturing practices and stored for long periods, at high antigen/vesicle mass ratios. However, their uptake by antigen-presenting cells (APC) at the inductive sites remains as a major challenge. As neurotoxicity is a major concern in intranasal delivery, complexes between archaeosomes and calcium as well as cationic liposomes complexed with plasmids encoding for antigenic proteins could safely elicit secretory and systemic antigen-specific immune responses. Oral bilosomes generate intense immune responses that remain to be tested against challenge, but the admixing with toxins or derivatives is mandatory to reduce the amount of antigen. Most of the current experimental designs, however, underestimate the mucus blanket 100- to 1000-fold thicker than a 100-nm diameter liposome, which has first to be penetrated to access the underlying M cells. Overall, designing mucoadhesive chemoenzymatic resistant liposomes, or selectively targeted to M cells, has produced less relevant results than tailoring the liposomes to make them mucus penetrating. Opposing, the nearly 10 µm thickness stratum corneum interposed between liposomes and underlying APC can be surpassed by ultradeformable liposomes (UDL), with lipid matrices that penetrate up to the limit with the viable epidermis. UDL made of phospholipids and detergents, proved to be better transfection agents than conventional liposomes and niosomes, without the toxicity of ethosomes, in the absence of classical immunomodulators. PMID:21360692

  18. Oxygen sensing in intestinal mucosal inflammation.

    PubMed

    Flck, Katharina; Fandrey, Joachim

    2016-01-01

    Hypoxia is a hallmark of chronically inflamed tissue. Hypoxia develops from vascular dysfunction and increased oxygen consumption by infiltrating leukocytes. With respect to inflammatory bowel disease (IBD), hypoxia is likely to be of particular importance: Impairment of the intestinal barrier during IBD allows anoxia from the lumen of the gut to spread to formerly normoxic tissue. In addition, disturbed perfusion of inflamed tissue and a higher oxygen demand of infiltrating immune cells lead to low oxygen levels in inflamed mucosal tissue. Here, cells become hypoxic and must now adapt to this condition. The hypoxia inducible factor (HIF)-1 complex is a key transcription factor for cellular adaption to low oxygen tension. HIF-1 is a heterodimer formed by two subunits: HIF-? (either HIF-1? or HIF-2?) and HIF-1?. Under normoxic conditions, hydroxylation of the HIF-? subunit by specific oxygen-dependent prolyl hydroxylases (PHDs) leads to ubiquitin proteasome-dependent degradation. Under hypoxic conditions, however, PHD activity is inhibited; thus, HIF-? can translocate into the nucleus, dimerize with HIF-1?, and bind to hypoxia-responsive elements of HIF-1 target genes. So far, most studies have addressed the function of HIF-1? in intestinal epithelial cells and the effect of HIF stabilization by PHD inhibitors in murine models of colitis. Furthermore, the role of HIF-1? in immune cells becomes more and more important as T cells or dendritic cells for which HIF-1 is of critical importance are highly involved in the pathogenesis of IBD. This review will summarize the function of HIF-1? and the therapeutic prospects for targeting the HIF pathway in intestinal mucosal inflammation. PMID:26206140

  19. Use of homoarginine for measuring true ileal digestibility of amino acids in food protein.

    PubMed

    Yin, Jie; Ren, Wenkai; Hou, Yongqing; Wu, Miaomiao; Xiao, Hao; Duan, Jielin; Zhao, Yurong; Li, Tiejun; Yin, Yulong; Wu, Guoyao; Nyachoti, C M

    2015-09-01

    A useful application of homoarginine in animal nutrition is the determination of the true ileal digestibility (TID) of amino acids (AA) in swine complete diets and feed ingredients. The homoarginine method involves the conversion of dietary lysine to homoarginine in a guanidination reaction with methylisourea. Accurate determination of TID of AA, especially in heat-treated feed ingredients, is a key prerequisite for accurate diet formulation with respect to the provision of dietary AA. Thus, the aim of this review is to highlight the homoarginine methodology and its application in animal nutrition. Based on the data from published studies, the homoarginine method can be used to accurately determine the digestibility of lysine and the majority of other acid-stable AA in complete diets and feed ingredients fed to animals. PMID:25894888

  20. Laparoscopic restorative proctocolectomy ileal pouch anal anastomosis: How I do it?

    PubMed

    Madnani, Manish A; Mistry, Jitendra H; Soni, Harshad N; Shah, Atul J; Patel, Kantilal S; Haribhakti, Sanjiv P

    2015-01-01

    Surgery for ulcerative colitis is a major and complex colorectal surgery. Laparoscopy benefits these patients with better outcomes in context of cosmesis, pain and early recovery, especially in young patients. For surgeons, it is a better tool for improving vision and magnification in deep cavities. This is not the simple extension of the laparoscopy training. Starting from preoperative preparation to post operative care there are wide variations as compared to open surgery. There are also many variations in steps of laparoscopic surgery. It involves left colon, right colon and rectal mobilisation, low division of rectum, pouch creation and anastomosis of pouch to rectum. Over many years after standardisation of this technique, it takes same operative time as open surgery at our centre. So we present our standardized technique of laparoscopic assisted restorative proctocolectomy and ileal pouch anal anastomosis (IPAA). PMID:26195886

  1. Malignant familial adenomatous polyposis treated by laparoscopic colectomy and ileal pouch anal anastomosis: a case report.

    PubMed

    Zaharie, Florin; Ciorogar, George; Zaharie, Roxana; Tantau, Marcel; Iancu, Cornel; Mocan, Lucian

    2014-12-01

    The mean age of colorectal cancer in untreated familial adenomatous polyposis (FAP) is 39 years. We present the case of a 21-year-old patient with FAP and colorectal cancer. The patient was detected with significant family history: her mother died at age 45 with colon cancer; two uncles were diagnosed with colon cancer at the age of 40 and 43 and one aunt at the age of 45 with colon cancer and gastric cancer. The treatment was laparoscopic restorative proctocolectomy with total excision of the mesorectum and ileal pouch anal anastomosis completed with endoanal excision of inferior rectal polyps. The histopathological report described a well differentiated rectal adenocarcinoma T1N1aMx developed on a tubulo-villous adenoma located on the rectosigmoid jonction, the rest of the polyps with benign histology. PMID:25532006

  2. Hand-Assisted Laparoscopic Versus Open Restorative Proctocolectomy With Ileal Pouch Anal Anastomosis

    PubMed Central

    Maartense, Stefan; Dunker, Michalda S.; Slors, J Frederick; Cuesta, Miguel A.; Gouma, Dirk J.; van Deventer, Sander J.; van Bodegraven, Ad A.; Bemelman, Willem A.

    2004-01-01

    Objective: The aim of the study was to evaluate postoperative recovery after hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis in a randomized controlled trial. Methods: Sixty patients were randomized for hand-assisted laparoscopic (n = 30) or open surgery (n = 30). Primary outcome parameter was postoperative recovery in the 3 months after surgery, measured by quality of life questionnaires (SF-36 and GIQLI). Secondary parameters were postoperative morphine requirement and surgical parameters, viz. operating time, morbidity, hospital stay, and costs. Results: There was no difference between the 2 procedures in quality of life assessment in the 3 months after surgery. There was a significant decline in quality of life on all scales of the SF-36 (P < 0.001) and total GIQLI score (P < 0.001) in the first 2 weeks in both groups (no significant difference between the groups). Quality of life returned to baseline levels after 4 weeks. Operating times were longer in the laparoscopic group compared with the open group (210 and 133 minutes, respectively; P < 0.001). No significant differences were found in morphine requirement. Neither morbidity nor postoperative hospital stay differed between the laparoscopic and open group (20% versus 17%, in 10 versus 11 days, respectively). Median overall costs were € 16.728 for the hand-assisted laparoscopic procedure and € 13.406 for the open procedure (P = 0.095). Conclusions: Recovery measured using quality of life questionnaires is comparable for hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis. The laparoscopic approach is as safe, but more costly than the open procedure. PMID:15570204

  3. Nutrient digestion by ileal cannulated dogs as affected by dietary fibers with various fermentation characteristics.

    PubMed

    Muir, H E; Murray, S M; Fahey, G C; Merchen, N R; Reinhart, G A

    1996-07-01

    We studied the effects of dietary fibers with various fermentation characteristics on nutrient digestion at the distal ileum and in the total tract of dogs. The following high-protein (34%), high-fat (23%) diets were fed: 1) a control treatment (CON) with 0% supplemental fiber; 2) beet pulp (BP), 7.5%; 3) low-cellulose mixture (LCM), 2.5% cellulose + 5.0% pectin; 4) high-cellulose mixture (HCM), 5.0% cellulose + 2.5% pectin; or 5) Solka Floc (SF), 7.5% cellulose. Nutrient intakes by fiber-supplemented dogs were similar among treatment groups but greater (P < .05) than for dogs fed the control diet. Digestion of nutrients at the distal ileum was similar among groups except for fat: the dogs fed BP digested less fat than those fed the other sources of dietary fiber. Digestion of amino acids at the distal ileum was similar for all groups, except for lysine, which increased (P < .05) in digestibility as dietary cellulose concentration increased. Dogs consuming LCM had lower apparent ileal digestibility values for all nutrients, including most amino acids, than dogs consuming HCM or SF. Total tract digestion of DM and OM by dogs fed supplemental fiber was less (P < .05) than for dogs fed the control diet. The BP treatment was higher than other fiber treatments in total tract digestion of OM (P < .10) and total dietary fiber (P < .05). Total tract digestibilities of all nutrients exhibited either linear or quadratic responses to dietary cellulose concentrations. Apparent ileal and total tract nutrient digestion was influenced by the source of dietary fiber consumed. PMID:8818810

  4. 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

  5. Corticotropin-releasing hormone acts on guinea pig ileal smooth muscle via protein kinase A.

    PubMed

    Duridanova, D B; Petkova-Kirova, P S; Lubomirov, L T; Gagov, H; Boev, K

    1999-07-01

    In contraction studies corticotropin-releasing hormone (CRH) was found to relax ileal but not gastric and jejunal smooth muscles of the guinea-pig, precontracted with BaCl2. Under whole-cell patch-clamp conditions, CRH concentration-dependently activated Ca2+-sensitive K+ currents (IK) with ED50=20 pM at 100 nM and ED50=0. 13 pM at 500 nM intracellular Ca2+ respectively. This increase was accompanied by significant hyperpolarization of the cell membranes. CRH 9-41 peptide fragment did not affect IK amplitude, membrane potential or contraction. The CRH-induced increase of IK densities was accelerated in the presence of high intracellular Ca2+ concentrations (500 nM) and was abolished by pretreatment of cells with either ryanodine or thapsigargin, which cause depletion of intracellular Ca2+ stores, as well as in cells treated under conditions prohibiting intracellular Ca2+ store refilling. The effect of CRH on IK was not affected by bath application of various selective inhibitors of membrane-bound phospholipases, protein kinase C, cGMP-dependent protein kinase or Ca2+/calmodulin-dependent protein kinase II, but was effectively antagonized by blockers of protein kinase A (PKA) or adenylyl cyclase. Neither forskolin nor the catalytic subunit of PKA could mimic the effect of CRH on IK. Thus, it was suggested that CRH exerts its relaxing activity on ileal smooth muscle cells via PKA-dependent phosphorylation of some intracellular target coupled to sarcoplasmic reticulum Ca2+ storage machinery. PMID:10370107

  6. Emptying of the terminal ileum in intact humans. Influence of meal residue and ileal motility

    SciTech Connect

    Spiller, R.C.; Brown, M.L.; Phillips, S.F.

    1987-03-01

    Emptying of the terminal ileum was assessed in 15 healthy humans by injecting technetium 99m-diethyltriaminopentaacetic acid into the bowel through a multilumen orocolonic tube. The subsequent arrival of isotope in the colon was quantified by gamma-scintigraphy and colonic filling curves were obtained. Studies were performed during fasting (n = 5) cnd 2.5 h after either a low residue meal (n = 5) or a meal made high in residue (n = 5) by adding 4 g of guar. The time for 50% of the isotope to reach the colon (T50) was significantly accelerated after both meals, being 72 +/- 15 min for the high residue meal and 62 +/- 8 min for the low residue meal, compared with 183 +/- 37 min (p less than 0.01) in the 5 fasting subjects. Although the addition of guar did not alter T50 significantly, it did cause a significant fall in the rate of colonic filling, implying increased isotope dilution. Delay at the ileocolonic junction, as shown by plateaus in the middle of the colonic filling curves, was uncommon. Hold-up was significant in only 2 of 10 postprandial and 2 of 5 fasting studies. Rates of ileocolonic transit could not be related to either a mean ileal motility index or the occurrence of specific ileal motor patterns immediately proximal to the ileocolonic junction. Fasting ileocolonic transit was characteristically erratic but could not be related to interdigestive migrating motor complexes, which were rarely observed in the last 60 cm of ileum. We conclude that ileocolonic transit in humans is related to the rate at which material accumulates in the ileum, being rapid postprandially and slow and erratic during fasting. This method yields consistent results and could be used to define further factors that influence ileocolonic inflow.

  7. Inhibitory effects of indicaxanthin on mouse ileal contractility: analysis of the mechanism of action.

    PubMed

    Baldassano, Sara; Rotondo, Alessandra; Serio, Rosa; Livrea, Maria Antonietta; Tesoriere, Luisa; Mul, Flavia

    2011-05-11

    Recently, we have showed that indicaxanthin, the yellow betalain pigment abundant in the fruit of Opuntia ficus indica, has remarkable spasmolytic effects on the intestinal contractility in vitro. Thus, the purpose of the present study was to investigate the mechanism of action underlying the observed response. We used organ bath technique to record the mechanical activity of the mouse ileum longitudinal muscle and ELISA to measure the levels of cAMP. Indicaxanthin induced inhibitory effects on spontaneous mechanical activity, which were unaffected by indomethacin, a non-selective inhibitor of cycloxygenase; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a selective inhibitor of nitric oxide-dependent guanylyl cyclase; 2'5'dideoxyadenosine, an adenylyl cyclase inhibitor; and zaprinast, a selective inhibitor of the cGMP phosphodiesterase isoenzyme. Indicaxanthin effects were reduced significantly in the presence of 3-isobutyl-1-methylxanthine (IBMX), a non selective inhibitor of phosphodiesterases (PDEs). Indicaxanthin and IBMX significantly reduced the carbachol-evoked contractions and the joint application of both drugs did not produce any additive effect. Indicaxanthin and IBMX increased the inhibitory effects of forskolin, an adenylyl cyclase activator, and the joint application of both drugs did not produce any additive effect. Indicaxanthin, contrarily to IBMX, did not affect the inhibitory action of sodium nitroprusside, a soluble guanylyl cyclase activator. Indicaxanthin increased both basal and forskolin-induced cAMP content of mouse ileal muscle. The present data show that indicaxanthin reduces the contractility of ileal longitudinal muscle by inhibition of PDEs and increase of cAMP concentration and raise the possibility of using indicaxanthin in the treatment of motility disorders, such as abdominal cramps. PMID:21371457

  8. Effects of dietary supplementation with a protease on the apparent ileal digestibility of the weaned piglet.

    PubMed

    Guggenbuhl, P; Waché, Y; Wilson, J W

    2012-12-01

    The effects of an acid-stable protease (RONOZYME ProAct) supplemented to a corn (Zea mays)-soybean (Glycine max) meal-based diet on apparent ileal digestibility (AID) of nutrients were evaluated in 120 weaned piglets (28 d old; 8.17 ± 0.90 kg). Pigs were divided into 2 equal groups and had free access to mash diet containing 0.4% Cr(2)O(3) as indigestible marker [basal diet (Std)] or this diet supplemented with RONOZYME ProAct at 15,000 PROT [the amount of enzyme that releases 1 μmol of pnitroaniline from 1 μM of substrate (Suc-Ala-Ala-Pro-Phe-p-nitroaniline) per min at pH 9.0 and 37°C)/kg (ProA). The ileal content was collected for the digestibility determination after euthanasia of 35 piglets of each group after 14 d of study and 25 piglets of each group after 29 d. Compared to group Std, AID of CP was increased (P < 0.05) after 29 d of treatment in group ProA. The AID of the indispensable AA, Met + Cys, and branched-chain AA was increased (P < 0.05) at the end of the study. In the protease supplemented pigs, the AID of the individual AA was not improved after 14 d of treatment whereas it was increased (P < 0.05) at the end of the experiment for Arg, Asp + Asn, Glu + Gln, His, Ile, Lys, Phe, Thr, Tyr ,and Val. In conclusion, dietary protease supplementation increased AID of AA in piglets. PMID:23365313

  9. Lactobacillus rhamnosus GG on rotavirus induced injury of ileal epithelium in gnotobiotic pigs

    PubMed Central

    Liu, Fangning; Li, Guohua; Wen, Ke; Wu, Shaoping; Zhang, Yongguo; Bui, Tammy; Yang, Xingdong; Kocher, Jacob; Sun, Jun; Jortner, Bernard; Yuan, Lijuan

    2013-01-01

    Objectives To study the impact of continued LGG feeding on rotavirus gastroenteritis in the gnotobiotic pig (Gn) model of virulent human rotavirus (HRV) infection. Methods Gn pigs were assigned to treatment groups: (1) mock control, (2) LGG only, (3) HRV only or (4) LGG plus HRV. Nine days before HRV inoculation (3 days of age), pigs were fed LGG with a daily dose increase of 10-fold from 103 until 1012 colony forming units (CFU). The 1012 CFU/dose of LGG feeding continued until post-HRV-inoculation day (PID) 6. Clinical sign (diarrhea), rotavirus fecal shedding, histopathology of the ileum, adherent junction and tight junction protein expression in the ileal epithelial cells, mucin production in the large and small intestinal contents, and serum cytokine responses from PID 2 to PID 6 were examined and compared among the treatment groups. Results Clinically, the percentage of pigs developing diarrhea, the mean duration of diarrhea, and the mean cumulative fecal scores were lower in the LGG fed pigs compared to the non-fed pigs after HRV inoculation. LGG partially protected ileal epithelium against HRV-induced compensatory increases of the adherent junction protein α-catenin and β-catenin, tight junction protein occludin, claudin-3 and claudlin-4, and leak protein claudin-2. LGG promoted mucin production as the mucin levels in the large intestinal contents of the LGG+HRV pigs were significantly higher than the HRV only pigs on PID 2. Additionally, LGG maintained the anti-inflammatory cytokine TGF-β level in serum after HRV infection. Conclusions LGG is moderately effective for ameliorating rotavirus diarrhea by partially preventing injuries to the epithelium. PMID:24280990

  10. Targeted deletion of the ileal bile acid transporter eliminates enterohepatic cycling of bile acids in mice.

    PubMed

    Dawson, Paul A; Haywood, Jamie; Craddock, Ann L; Wilson, Martha; Tietjen, Mary; Kluckman, Kimberly; Maeda, Nobuyo; Parks, John S

    2003-09-01

    The ileal apical sodium bile acid cotransporter participates in the enterohepatic circulation of bile acids. In patients with primary bile acid malabsorption, mutations in the ileal bile acid transporter gene (Slc10a2) lead to congenital diarrhea, steatorrhea, and reduced plasma cholesterol levels. To elucidate the quantitative role of Slc10a2 in intestinal bile acid absorption, the Slc10a2 gene was disrupted by homologous recombination in mice. Animals heterozygous (Slc10a2+/-) and homozygous (Slc10a2-/-) for this mutation were physically indistinguishable from wild type mice. In the Slc10a2-/- mice, fecal bile acid excretion was elevated 10- to 20-fold and was not further increased by feeding a bile acid binding resin. Despite increased bile acid synthesis, the bile acid pool size was decreased by 80% and selectively enriched in cholic acid in the Slc10a2-/- mice. On a low fat diet, the Slc10a2-/- mice did not have steatorrhea. Fecal neutral sterol excretion was increased only 3-fold, and intestinal cholesterol absorption was reduced only 20%, indicating that the smaller cholic acid-enriched bile acid pool was sufficient to facilitate intestinal lipid absorption. Liver cholesteryl ester content was reduced by 50% in Slc10a2-/- mice, and unexpectedly plasma high density lipoprotein cholesterol levels were slightly elevated. These data indicate that Slc10a2 is essential for efficient intestinal absorption of bile acids and that alternative absorptive mechanisms are unable to compensate for loss of Slc10a2 function. PMID:12819193

  11. Effects of feed additives on ileal mucosa-associated microbiota composition of broiler chickens.

    PubMed

    Ruiz, R; Peinado, M J; Aranda-Olmedo, I; Abecia, L; Surez-Pereira, E; Ortiz Mellet, C; Garca Fernndez, J M; Rubio, L A

    2015-07-01

    The effects of dietary supplementation with 2 recently developed feed additives on the composition of the mucosa-associated microbiota of the ileum were studied in growing broiler chickens. A total of 48 male 1-d-old broiler chickens of the Cobb 500 strain were distributed in 4 treatments with 2 replicates of 6 birds each. The 2 additives tested were a di-d-fructose dianhydrideenriched caramel (FC) and the garlic derivative propyl propane thiosulfonate (PTS-O). Dietary treatments were a control (commercial diet with no additive), INU (20 g inulin/kg diet), CAR (20 g FC/kg diet), and GAR (90 mgPTS-O/kg diet). As a result of this study, inulin supplementation resulted in lower (P < 0.05) and FC feeding resulted in higher (P < 0.05) Blautia coccoides/Eubacterium rectale log10 number of copies respect to controls. Higher (P < 0.05) bifidobacteria log10 number of copies with respect to the controls was determined in the ileal mucosa of birds fed the PTS-Osupplemented diet. Denaturing gradient gel electrophoresis and PCR analysis on Bifidobacterium spp. revealed the presence of Bifidobacterium longum, Bifidobacterium pseudolongum, and Bifidobacterium pseudocatenulatum in samples from chickens fed the control and the PTS-Osupplemented diet. Bifidobacterium longum was exclusively found in poultry fed the control diet, whereas B. pseudocatenulatum was found only in poultry fed the PTS-Osupplemented diet. This study showed that both PTS-O and FC were able to modulate the composition of the ileal mucosa-associated microbiota of growing broiler chickens. Finally, in addition to B. pseudolongum, the presence of B. longum and B. pseudocatenulatum, species not previously described in intestinal samples of broilers, was also demonstrated. PMID:26440010

  12. The mucosal immune system: From dentistry to vaccine development.

    PubMed

    Kiyono, Hiroshi; Azegami, Tatsuhiko

    2015-01-01

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

  13. Implication of nanoparticles/microparticles in mucosal vaccine delivery.

    PubMed

    Vyas, Suresh P; Gupta, Prem N

    2007-06-01

    Although polymeric nanoparticles/microparticles are well established for the mucosal administration of conventional drugs, they have not yet been developed commercially for vaccine delivery. The limitation of the mucosal (particularly oral) route of delivery, including low pH, gastric enzymes, rapid transit and poor absorption of large molecules, has made mucosal vaccine delivery challenging. Nevertheless, several polymeric delivery systems for mucosal vaccine delivery are currently being evaluated. The polymer-based approaches are designed to protect the antigen in the gut, to target the antigen to the gut-associated lymphoid tissue or to increase the residence time of the antigen in the gut through bioadhesion. M-cell targeting is a potential approach for mucosal vaccine delivery, which can be achieved using M-cell-specific lectins, microbial adhesins or immunoglobulins. While many hurdles must be overcome before targeted mucosal vaccine delivery becomes a practical reality, this is a potential area of research that has important implications for future vaccine development. This review comprises various aspects that could be decisive in the development of polymer based mucosal vaccine delivery systems. PMID:17542755

  14. 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. )

    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.

  15. Bilateral occult mucosal bridges of the true vocal folds.

    PubMed

    Gull, John; Divi, Venu; Ghaderi, Mahmoud; Sataloff, Robert T

    2009-11-01

    A mucosal bridge of the true vocal fold is a rare, benign anatomical finding that can cause dysphonia. It has been described by some in the literature as "occult" as it is often not visibly evident on flexible nasopharyngolaryngoscopy or strobovideolaryngoscopy, but mistakenly diagnosed as a sulcus vocalis (Sataloff RT, Rosen C, Hawkshaw M. Occult mucosal bridge of the vocal fold. Ear Nose Throat J. 1997; 76(12):850).(2) Final diagnosis is usually not made until microscopic direct laryngoscopy is performed and palpation of the true vocal fold reveals the mucosal bridge (Tanaka S, Hirano M, Umeno H, Tanaka Y. Mucosal bridge of the vocal fold [Japanese].(4)Nippon Jibiinkoka Gakkai Kaiho. 1991; 94(12):1853-1856). We describe a case of a 15-year-old boy complaining of long-standing hoarseness and found to have bilateral mucosal bridges of the true vocal folds. Previous reports cite cases of a unilateral mucosal bridge. We believe this is the first reported case of bilateral mucosal bridges. PMID:18619785

  16. The missing links in exercise effects on mucosal immunity.

    PubMed

    Gleeson, Maree; Pyne, David B; Callister, Robin

    2004-01-01

    This review highlights research limitations within the existing exercise immunology literature and summarises unanswered questions to assist researchers and clinicians interested in exploring relationships between exercise, training and mucosal immunity. The primary limitations of the existing literature include: inadequate descriptions of training stimuli, age, gender and physical activity of subjects; failing to account for the influence of these factors and the underlying fitness and health status of subjects; methodological differences in assessments of mucosal immunity; limited understanding of the sources of biological variability in mucosal immunity; limited clinical and laboratory diagnosis of respiratory illness; and neglect of psychological, environmental, nutritional and pharmacological influences. Despite a considerable volume of research on mucosal immunity the unanswered research questions include: whether athletes are really more prone to illness; whether illness impacts on athletic performance; identifying subject or training characteristics that influence the mucosal immune responses to exercise; defining how exercise influences the acute mucosal immune response; assessing whether moderate exercise can enhance mucosal immune status; defining more clearly the treatment and management strategies for the athlete suffering recurrent illness, overtraining or long-term fatigue; and the effectiveness of dietary and therapeutic interventions. Answers to these questions should define future research strategies and assist clinicians seeking guidance on the assessment, treatment and management of athletes suffering from respiratory illness, particularly those with recurrent illness, long-term post-viral fatigue or suspected of being overtrained. PMID:15633590

  17. Mucosal adenosine stimulates chloride secretion in canine tracheal epithelium

    SciTech Connect

    Pratt, A.D.; Clancy, G.; Welsh, M.J.

    1986-08-01

    Adenosine is a local regulator of a variety of physiological functions in many tissues and has been observed to stimulate secretion in several Cl-secreting epithelia. In canine tracheal epithelium the authors found that adenosine stimulates Cl secretion from both the mucosal and submucosal surfaces. Addition of adenosine, or its analogue 2-chloroadenosine, to the mucosal surface potently stimulated Cl secretion with no effect on the rate of Na absorption. Stimulation resulted from an interaction of adenosine with adenosine receptors, because it was blocked by the adenosine receptor blocker, 8-phenyltheophylline. The adenosine receptor was a stimulatory receptor as judged by the rank-order potency of adenosine and its analogues and by the increase in cellular adenosine 3',5'-cyclic monophosphate levels produced by 2-chloroadenosine. Adenosine also stimulated Cl secretion when it was added to the submucosal surface, although the maximal increase in secretion was less and it was much less potent. The observation that mucosal 8-phenyletheophylline blocked the effect of submucosal 2-chloroadenosine, whereas submucosal 8-phenyltheophylline did not prevent a response to mucosal or submucosal 2-chloroadenosine, suggests that adenosine receptors are located on the mucosal surface. Thus submucosal adenosine may stimulate secretion by crossing the epithelium and interacting with receptors located on the mucosal surface. Because adenosine can be released from mast cells located in the airway lumen in response to inhaled material, and because adenosine stimulated secretion from the mucosal surface, it may be in a unique position to control the epithelium on a regional level.

  18. Oral Mucosal Lesions in Indians From Northeast Brazil

    PubMed Central

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

    2014-01-01

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

  19. Glutathione: an overview of biosynthesis and modulation.

    PubMed

    Anderson, M E

    1998-04-24

    Glutathione (GSH; gamma-glutamylcysteinylglycine) is ubiquitous in mammalian and other living cells. It has several important functions, including protection against oxidative stress. It is synthesized from its constituent amino acids by the consecutive actions of gamma-glutamylcysteine synthetase and GSH synthetase. gamma-Glutamylcysteine synthetase activity is modulated by its light subunit and by feedback inhibition of the end product, GSH. Treatment with an inhibitor, buthionine sulfoximine (BSO), of gamma-glutamylcysteine synthetase leads to decreased cellular GSH levels, and its application can provide a useful experimental model of GSH deficiency. Cellular levels of GSH may be increased by supplying substrates and GSH delivery compounds. Increasing cellular GSH may be therapeutically useful. PMID:9679538

  20. Glutathione-Dependent Detoxification Processes in Astrocytes.

    PubMed

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

    2015-12-01

    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

  1. 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

  2. Nanofiltration concentration of extracellular glutathione produced by engineered Saccharomyces cerevisiae.

    PubMed

    Sasaki, Kengo; Hara, Kiyotaka Y; Kawaguchi, Hideo; Sazuka, Takashi; Ogino, Chiaki; Kondo, Akihiko

    2016-01-01

    This study aimed to optimize extracellular glutathione production by a Saccharomyces cerevisiae engineered strain and to concentrate the extracellular glutathione by membrane separation processes, including ultrafiltration (UF) and nanofiltration (NF). Synthetic defined (SD) medium containing 20gL(-1) glucose was fermented for 48h; the fermentation liquid was passed through an UF membrane to remove macromolecules. Glutathione in this permeate was concentrated for 48h to 545.133.6mgL(-1) using the NF membrane; this was a significantly higher concentration than that obtained with yeast extract peptone dextrose (YPD) medium following 96h NF concentration (217.957.4mgL(-1)). This higher glutathione concentration results from lower cellular growth in SD medium (final OD600=6.90.1) than in YPD medium (final OD600=11.00.6) and thus higher production of extracellular glutathione (16.01.3 compared to 9.22.1mgL(-1) in YPD medium, respectively). Similar fermentation and membrane processing of sweet sorghum juice containing 20gL(-1) total sugars provided 240.360.6mgL(-1) glutathione. Increased extracellular production of glutathione by this engineered strain in SD medium and subsequent UF permeation and NF concentration in shortend time may help realize industrial recovery of extracellular glutathione. PMID:26105794

  3. Maturation of cytosolic iron-sulfur proteins requires glutathione.

    PubMed

    Sipos, Katalin; Lange, Heike; Fekete, Zsuzsanna; Ullmann, Pascaline; Lill, Roland; Kispal, Gyula

    2002-07-26

    Glutathione is the major protective agent against oxidative stress in Saccharomyces cerevisiae. Deletion of the GSH1 gene (strain Deltagsh1) encoding the enzyme that catalyzes the first step of glutathione biosynthesis leads to growth arrest, which can be relieved by either glutathione or reducing agents such as dithiothreitol. Because defects in the biosynthesis of cellular iron-sulfur (Fe/S) proteins are associated with increases in glutathione levels, we examined the consequences of glutathione depletion on this essential process. No significant defects were detected in the amounts, activities, and maturation of mitochondrial Fe/S proteins in glutathione-depleted Deltagsh1 cells. On the contrary, the maturation of extra-mitochondrial Fe/S proteins was decreased substantially. The defect was rectified neither by addition of dithiothreitol nor under anaerobic conditions excluding oxidative damage of Fe/S clusters. A double mutant in GSH1 and ATM1 encoding a mitochondrial ATP binding cassette (ABC) transporter involved in cytosolic Fe/S protein maturation is nonviable even in the presence of dithiothreitol. Similar to atm1 and other mutants defective in cytosolic Fe/S protein maturation, mitochondria from glutathione-depleted Deltagsh1 cells accumulated high amounts of iron. Together, our data demonstrate that glutathione, in addition to its protective role against oxidative damage, performs a novel and specific function in the maturation of cytosolic Fe/S proteins. PMID:12011041

  4. 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

  5. Engineering immunity in the mucosal niche against sexually transmitted infections.

    PubMed

    Ramanathan, Renuka; Woodrow, Kim

    2016-01-01

    The mucosal surfaces of the genital tract are the site of entry to over 30 different bacterial, parasitic, and viral pathogens that are the cause of sexually transmitted infections (STIs) including HIV. Women and adolescent girls are more severely impacted by STIs than men due in part to a greater biological susceptibility for acquiring infections and differences in disease sequelae. While it is widely accepted that preventative vaccines against the most commonly transmitted STIs would have a major impact on decreasing the global health burden of STIs for women worldwide, several challenges preclude their development. The female genital tract is a complex niche of microflora, hormonal influences, and immune tissues and cells that result in a mucosal immune system that is distinct from other mucosal sites and from our systemic immune system. An appreciation of these differences and their effect on shaping mucosal immunity to sexually transmitted pathogens is an important determinant for the design of effective STI vaccines. Here we describe the anatomy and mucosal immune system of the female reproductive tract, and discuss bioengineering strategies to design mucosal vaccines that overcome delivery challenges and coordinate the presentation kinetics and compartmentalization of antigens and adjuvants to relevant mucosal immune cell subsets. In particular, we describe recent progress in understanding the role of specific mucosal dendritic cell subsets in facilitating immune responses to pathogenic microbes in the genital mucosa. We also discuss the development of pathogen-mimicking materials that may be useful for engineering protective immunity in this mucosal niche. WIREs Nanomed Nanobiotechnol 2015, 8:107-122. doi: 10.1002/wnan.1359 For further resources related to this article, please visit the WIREs website. PMID:26153141

  6. Ultrasensitive microfluidic array for serum pro-inflammatory cytokines and C-reactive protein to assess oral mucositis risk in cancer patients.

    PubMed

    Krause, Colleen E; Otieno, Brunah A; Bishop, Gregory W; Phadke, Gayatri; Choquette, Linda; Lalla, Rajesh V; Peterson, Douglas E; Rusling, James F

    2015-09-01

    In addition to disease diagnostics, there is a need for biomarkers to predict severity of cancer therapy side effects such as oral mucositis. Oral mucositis is an inflammatory lesion of oral mucosa caused by high-dose chemotherapy and/or radiation that is especially prevalent during oral cancer treatment. We describe here a semi-automated, modular microfluidic immunoarray optimized for ultrasensitive detection of pro-inflammatory cytokines involved in pathobiology of oral mucositis. Our goal is to methodologically identify risk of mucositis early in oral cancer treatment, before the onset of lesions. Biomarkers include tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and C-reactive protein (CRP). Protein analytes were captured from serum in a capture chamber by 1-μm magnetic beads coated with antibodies and enzyme labels. Beads are then transported downstream to a detection chamber containing an eight-sensor array coated with glutathione-coated gold nanoparticles (GSH-AuNP) and a second set of antibodies to capture the beads with analyte proteins. In this first application of the immunoarray to four-protein multiplexed measurements, ultralow detection limits of 10-40 fg mL(-1) in 5 μL serum were achieved for simultaneous detection in 30 min. Mass detection limits were 2.5-10 zmol, as few as 1500 molecules. Accuracy and diagnostic utility of the arrays were demonstrated by correlation of levels of the four biomarker proteins in serum from head and neck cancer patients with results from standard ELISA. This approach may lead to rapid, low-cost estimates of projected risk for severity of oral mucositis in cancer patients to enable improved therapeutic management. PMID:26143063

  7. Immunomodulators and delivery systems for vaccination by mucosal routes.

    PubMed

    Ryan, E J; Daly, L M; Mills, K H

    2001-08-01

    Current paediatric immunization programmes include too many injections in the first months of life. Oral or nasal vaccine delivery eliminates the requirement for needles and can induce immunity at the site of infection. However, protein antigens are poorly immunogenic when so delivered and can induce tolerance. Novel ways to enhance immune responses to protein or polysaccharide antigens have opened up new possibilities for the design of effective mucosal vaccines. Here, we discuss the immunological principles underlying mucosal vaccine development and review the application of immunomodulatory molecules and delivery systems to the selective enhancement of protective immune responses at mucosal surfaces. PMID:11451471

  8. 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

  9. Endoscopic management of mucosal lesions in the gastrointestinal tract.

    PubMed

    Chen, Wei-Chung; Wallace, Michael B

    2016-04-01

    With the increasing role of endoscopy in patient evaluation, more mucosal lesions, including gastric, duodenal and colonic polyps, are encountered during routine examinations. It is imperative for gastroenterologists to become familiar with the endoscopic management of these various gastrointestinal lesions. In this article, various resection techniques will be discussed, including hot/cold forceps polypectomy, hot/cold snare polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection. The article will also discuss the evidence regarding the efficacy and safety of these techniques and the future direction of endoscopic management of mucosal lesions in the gastrointestinal tract. PMID:26581857

  10. New perspectives in vaccine development: mucosal immunity to infections.

    PubMed

    McGhee, J R; Kiyono, H

    1993-04-01

    In this review, we focus on six key areas currently receiving attention in the mucosal immune system. These six areas are of considerable importance for development of vaccines. They are (a) the necessity to understand the unique features of the mucosal immune system; (b) the possibility that the common mucosal immune system may contain distinct compartments; (c) differences in antigen uptake and in types of antigen-presenting cells in mucosal inductive and effector sites; (d) more careful consideration of mucosal memory in vaccine development; (e) recent studies, which show that oral vaccines induce T-helper (Th)-cell subsets that regulate mucosal IgA responses; and (f) the mechanisms whereby mucosal S-IgA and T cells provide mucosal immune protection. An example of the above suffices to illustrate why the selected areas are of importance in vaccine development. Oral immunization preferentially induces type 2 Th (Th2) cell responses that directly correlate with antigen-specific IgA responses in mucosal effector sites. It is likely that activated, antigen-specific Th2 cells that are induced in Peyer's patches are continuously supplied to mucosal effector sites for regulation of IgA responses. These Th2 cells are producing cytokines such as interleukin (IL)-5 and IL-6 and these cytokines may direct antigen-specific surface IgA-positive B cells to become IgA-producing plasma cells. Nevertheless, additional studies will be required to establish that IgA responses to T-cell-dependent antigens depend on Th2 cell-derived help. What are the implications of these studies for current oral vaccines, including novel antigen delivery systems? The most obvious would be that vaccines should be optimized for induction of Th2-cell responses in IgA inductive sites such as the gut-associated lymphoreticular tissues. It is now clear that induction of Th2-type responses in both mucosal inductive and mucosal effector sites are essential for oral vaccines to induce S-IgA responses. However, antigens delivered by live vectors such as Salmonella typhimurium in the murine system and S. typhi in humans must consider T-cell responses induced against a live vector in addition to the inserted recombinant antigen. In this regard, it has been shown that these microorganisms induce cell-mediated immunity responses that largely result from Th1-type cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8162356

  11. Tolerance of gastric mucosal flap to postoperative irradiation

    SciTech Connect

    Devineni, V.R.; Hayden, R.; Fredrickson, J.; Sicard, G. )

    1991-05-01

    When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered.

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

    PubMed

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

    2016-01-01

    The objective of the study that is presented herein was to determine the true ileal calcium (Ca) digestibility in meat and bone meal (MBM) for broiler chickens using the direct method. Four MBM samples (coded as MBM-1, MBM-2, MBM-3 and MBM-4) were obtained and analyzed for nutrient composition, particle size distribution and bone to soft tissue ratio. The Ca concentrations of MBM-1, MBM-2, MBM-3 and MBM-4 were determined to be 71, 118, 114 and 81 g/kg, respectively. The corresponding geometric mean particle diameters and bone to soft tissue ratios were 0.866, 0.622, 0.875 and 0.781 mm, and 1:1.49, 1:0.98, 1:0.92 and 1:1.35, respectively. Five experimental diets, including four diets with similar Ca concentration (8.3 g/kg) from each MBM and a Ca and phosphorus-free diet, were developed. Meat and bone meal served as the sole source of Ca in the MBM diets. Titanium dioxide (3 g/kg) was incorporated in all diets as an indigestible marker. Each experimental diet was randomly allotted to six replicate cages (eight birds per cage) and offered from d 28 to 31 post-hatch. Apparent ileal Ca digestibility was calculated by the indicator method and corrected for ileal endogenous Ca losses to determine the true ileal Ca digestibility. Ileal endogenous Ca losses were determined to be 88 mg/kg dry matter intake. True ileal Ca digestibility coefficients of MBM-1, MBM-2, MBM-3 and MBM-4 were determined to be 0.560, 0.446, 0.517 and 0.413, respectively. True Ca digestibility of MBM-1 was higher (P < 0.05) than MBM-2 and MBM-4 but similar (P > 0.05) to that of MBM-3. True Ca digestibility of MBM-2 was similar (P > 0.05) to MBM-3 and MBM-4, while that of MBM-3 was higher (P < 0.05) than MBM-4. These results demonstrated that the direct method can be used for the determination of true Ca digestibility in feed ingredients and that Ca in MBM is not highly available as often assumed. The variability in true Ca digestibility of MBM samples could not be attributed to Ca content, percentage bones or particle size. PMID:26546671

  13. Selective Binding of Glutathione Conjugates of Fatty Acid Derivatives by Plant Glutathione Transferases*

    PubMed Central

    Dixon, David P.; Edwards, Robert

    2009-01-01

    Proteomic studies with Arabidopsis thaliana have revealed that the plant-specific Tau (U) class glutathione transferases (GSTs) are selectively retained by S-hexylglutathione affinity supports. Overexpression of members of the Arabidopsis GST superfamily in Escherichia coli showed that 25 of the complement of 28 GSTUs caused the aberrant accumulation of acylated glutathione thioesters in vivo, a perturbation that was not observed with other GST classes. Each GSTU caused a specific group of fatty acyl derivatives to accumulate, which varied in chain length (C6 to C18), additional oxygen content (0 or 1), and desaturation (0 or 1). Thioesters bound tightly to recombinant GSTs (Kd ∼ 1 μm), explaining their accumulation. Transient expression of GSTUs in Nicotiana benthamiana followed by recovery by Strep-tag affinity chromatography allowed the respective plant ligands to be extracted and characterized. Again, each GST showed a distinct profile of recovered metabolites, notably glutathionylated oxophytodienoic acid and related oxygenated fatty acids. Similarly, the expression of the major Tau protein GSTU19 in the endogenous host Arabidopsis led to the selective binding of the glutathionylated oxophytodienoic acid-glutathione conjugate, with the enzyme able to catalyze the conjugation reaction. Additional ligands identified in planta included other fatty acid derivatives including divinyl ethers and glutathionylated chlorogenic acid. The strong and specific retention of various oxygenated fatty acids by each GSTU and the conservation in binding observed in the different hosts suggest that these proteins have selective roles in binding and conjugating these unstable metabolites in vivo. PMID:19520850

  14. Glutathione regulates nitric oxide synthase in cultured hepatocytes.

    PubMed Central

    Harbrecht, B G; Di Silvio, M; Chough, V; Kim, Y M; Simmons, R L; Billiar, T R

    1997-01-01

    OBJECTIVE: The authors determine the relationship between glutathione and nitric oxide (NO) synthesis in cultured hepatocytes. SUMMARY BACKGROUND DATA: Glutathione is a cofactor for a number of enzymes, and its presence is essential for maximal enzyme activity by the inducible macrophage nitric oxide synthase (iNOS), which produces the reactive nitric oxide radical. Hepatocytes contain substantial quantities of glutathione, and this important tripeptide is decreased in hepatocytes stressed by ischemia/reperfusion or endotoxemia. Endotoxemia also induces the synthesis of inflammatory cytokines that result in the production of nitric oxide from hepatocytes by iNOS, suggesting that hepatocytes may be attempting to synthesize nitric oxide at times when intracellular glutathione is reduced. METHODS: Hepatocytes were cultured with buthionine sulfoximine and 1,3-bis(chloroethyl)-1-nitrosourea (BCNU) to inhibit glutathione. After exposure to cytokines, NO synthesis was assessed by supernatant nitrite levels, cytosolic iNOS enzyme activity, and iNOS mRNA levels. RESULTS: Inhibition of glutathione synthesis with buthionine sulfoximine or inhibition of glutathione reductase activity with BCNU inhibited nitrite synthesis. Both buthionine sulfoximine and BCNU inhibited the induction of iNOS mRNA, as detected by Northern blot analysis. Exogenous glutathione increased cytokine-stimulated iNOS induction, overcame the inhibitory effects of BCNU, and increased nitrite production by intact hepatocytes, induced hepatocyte cytosol, and partially purified hepatocyte iNOS. CONCLUSIONS: In cultured hepatocytes, adequate glutathione levels are required for optimal nitric oxide synthesis. This finding is predominantly due to an effect on iNOS mRNA levels, although glutathione also participates in the regulation of iNOS enzyme activity. Images Figure 4. Figure 5. Figure 6. PMID:8998123

  15. 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...

  16. 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...

  17. Biliary excretion of glutathione and glutathione disulfide in the rat. Regulation and response to oxidative stress.

    PubMed Central

    Lauterburg, B H; Smith, C V; Hughes, H; Mitchell, J R

    1984-01-01

    Regulation of the biliary excretion of reduced glutathione (GSH) and glutathione disulfide (GSSG) and responses to selected model toxins were examined in male Sprague-Dawley rats. In control and phenobarbital-pretreated rats in which the intrahepatic concentration of GSH was modulated by the administration of diethyl maleate or acetaminophen, the biliary concentration of GSH was consistently lower than, but directly proportional to, the intrahepatic concentration of GSH. Furthermore, increments in bile flow produced by the infusion of sulfobromophthalein (BSP)-glutathione were associated with proportional increases in the biliary excretion of GSH, suggesting that GSH passes into bile passively along a concentration gradient. In contrast, GSSG appears to be secreted into bile against a steep concentration gradient. An increased hepatic production and biliary excretion of GSSG resulted from the administration of t-butyl hydroperoxide. Measurement of biliary GSSG and BSP during a constant infusion of the GSH adduct of BSP indicated that GSSG shares a common excretory mechanism with GSH adducts. Diquat, nitrofurantoin, and paraquat also markedly stimulated the biliary excretion of GSSG. On a molar basis, these compounds generated much more GSSG than a direct substrate for glutathione peroxidase such as t-butyl hydroperoxide, indicating that the compounds undergo redox-cycling with concomitant production of hydrogen peroxide. Aminopyrine (0.8 mmol/kg) also significantly increased biliary GSSG. This increase, however, was associated with a proportional increase in bile flow and in the biliary excretion of GSH such that the GSSG/GSH ratio in bile did not change. Acetaminophen and chloroform, two compounds generating electrophilic metabolites that deplete intrahepatic GSH, led to a progressive decrease in the biliary excretion of GSH and GSSG. Furosemide and dimethylnitrosamine, the electrophilic metabolites of which do not deplete hepatic GSH, minimally altered biliary GSH and GSSG. Similarly, carbon tetrachloride and iproniazid, which yield organic radical metabolites that can peroxidize membrane lipids, did not increase the biliary excretion of GSSG. This finding indicates that membrane-bound lipid hydroperoxides may not be good substrates for glutathione peroxidases. The measurement of the biliary excretion of GSSG and of the GSSG/GSH ratio in bile is a sensitive index of oxidative stress in vivo and thus complements other in vivo parameters for the study of reactive intermediates of xenobiotics such as the determination of covalent binding, the formation of lipid hydroxy acids, and the depletion of intracellular GSH. PMID:6690473

  18. Determination of cellular glutathione:glutathione disulfide ratio in prostate cancer cells by high performance liquid chromatography with electrochemical detection.

    PubMed

    Childs, Stephen; Haroune, Nicolas; Williams, Lee; Gronow, Michael

    2016-03-11

    A validated method has been developed for the simultaneous measurement of reduced and oxidized glutathione in de-proteinised cellular extracts. This has been used to compare models of malignant and non-malignant human prostate cell lines. Analysis of LNCaP and DU145 cells showed a glutathione to glutathione disulfide ratio of 8:1 and 32:1 respectively, whilst the control cell line, PZ-HPV7 displayed a ratio of 93:1. Results indicate that the more aggressive phenotype displays adaptation to increased oxidative stress via up regulation of glutathione turnover. It was also noted that in the LNCaP and DU145 cell line, glutathione was only responsible for ca. 60% and 79% respectively, of the total cellular reduced thiol; indicating the presence of other biological thiols. PMID:26877179

  19. Recent advances in the development of novel mucosal adjuvants and antigen delivery systems.

    PubMed

    Chen, Wangxue; Patel, Girishchandra B; Yan, Hongbin; Zhang, Jianbing

    2010-09-17

    Mucosal infections and associated diseases remain a major socio-economic burden to society. Since parenteral immunizations fail to induce efficient protective immunity at mucosal surfaces, mucosal immunization is a logical approach to prevent and treat mucosally-initiated infections. All currently approved human mucosal vaccines are based on attenuated or killed whole pathogen cells but this strategy does pose safety concerns. Therefore, substantial effort is being invested to develop safe and effective mucosal adjuvants and delivery systems for mucosal vaccines. Encouragingly, some of these have progressed to advanced preclinical and clinical studies. This review discusses the promising preclinical research and the potential applications of several novel mucosal adjuvants and delivery systems: an archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) system, 3',5'-cyclic diguanylic acid (c-di-GMP) and detoxified bacterial AB(5) toxins. The potential and challenges in targeting M cells for mucosal vaccination are also discussed. PMID:20861683

  20. Review of Preclinical Studies on Treatment of Mucositis and Associated Pain

    PubMed Central

    Viet, C.T.; Corby, P.M.; Akinwande, A.; Schmidt, B.L.

    2014-01-01

    Oral mucositis is a significant problem in cancer patients treated with radiation or chemotherapy, often hindering definitive cancer treatment. For patients with oral mucositis, pain is the most distressing symptom, leading to loss of orofacial function and poor quality of life. While oral mucositis has been well-described, its pathophysiology is poorly understood. Oral health professionals treating patients with mucositis have almost no effective therapies to treat or prevent oral mucositis. The purpose of this review is to (1) describe the current preclinical models of oral mucositis and their contribution to the understanding of mucositis pathophysiology, (2) explore preclinical studies on therapies targeting mucositis and discuss the clinical trials that have resulted from these preclinical studies, and (3) describe the proposed pathophysiology of oral mucositis pain and preclinical modeling of oral mucositis pain. PMID:24943201

  1. Delivery systems: a vaccine strategy for overcoming mucosal tolerance?

    PubMed

    Mann, Jamie F S; Acevedo, Reinaldo; Campo, Judith Del; Pérez, Oliver; Ferro, Valerie A

    2009-01-01

    Antigens administered via the oral and, to a lesser extent, the nasal route are potentially able to invoke tolerance, resulting in a nonreactive immune response. This has been a hurdle for mucosal vaccine development and yet the desire to induce protective local and systemic responses, with pain-free and more convenient products, has been the impetus driving mucosal vaccine R&D. Nevertheless, few mucosal vaccines have reached the marketplace and products are still treated with caution, particularly where live organisms are utilized. In this review, we examine the use of delivery systems with adjuvant properties as key components in a vaccine strategy that does not require the use of live vectors to overcome tolerance and have exemplified their success in mucosal vaccines, concentrating on the nasal and oral routes of administration. PMID:19093777

  2. Recent advances in mucosal immunization using virus-like particles.

    PubMed

    Vacher, Gaëlle; Kaeser, Matthias D; Moser, Christian; Gurny, Robert; Borchard, Gerrit

    2013-05-01

    Mucosal immunization offers the promises of eliciting a systemic and mucosal immune response, as well as enhanced patient compliance. Mucosal vaccination using defined antigens such as proteins and peptides requires delivery systems that combine good safety profiles with strong immunogenicity, which may be provided by virus-like particles (VLP). VLP are assembled from viral structural proteins and thus are devoid of any genetic material. They excel by mimicking natural pathogens, therefore providing antigen-protecting particulate nature, inherent immune-cell stimulatory mechanisms, and tissue-specific targeting depending on their parental virus. Nevertheless, despite of promising preclinical results, VLP remain rarely investigated in clinical studies. This review is intended to give an overview of obstacles and promises of VLP-based mucosal immunization as well as to identify strategies to further improve VLP while maintaining a good safety and tolerability profile. PMID:23548071

  3. Physiology and immunology of mucosal barriers in catfish (Ictalurus spp.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mucosal barriers of catfish (Ictalurus spp.) constitute the first line of defense against pathogen invasion while simultaneously carrying out a diverse array of other critical physiological processes, including nutrient adsorption, osmoregulation, waste excretion, and environmental sensing. Catf...

  4. Gene, environment, microbiome and mucosal immune tolerance in rheumatoid arthritis.

    PubMed

    Catrina, Anca I; Deane, Kevin D; Scher, Jose U

    2016-03-01

    RA is a complex multifactorial chronic disease that transitions through several stages. Multiple studies now support that there is a prolonged phase in early RA development during which there is serum elevation of RA-related autoantibodies including RF and ACPAs in the absence of clinically evident synovitis. This suggests that RA pathogenesis might originate in an extra-articular location, which we hypothesize is a mucosal site. In discussing this hypothesis, we will present herein the current understanding of mucosal immunology, including a discussion about the generation of autoimmune responses at these surfaces. We will also examine how other factors such as genes, microbes and other environmental toxins (including tobacco smoke) could influence the triggering of autoimmunity at mucosal sites and eventually systemic organ disease. We will also propose a research agenda to improve our understanding of the role of mucosal inflammation in the development of RA. PMID:25539828

  5. 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 (5.79010?5 M/kg) was used as a reference medicine. The pre-treatment with the zinc (II) complex (2.18110?5 and 4.36210?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 (<87.24110?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

  6. Analyzing the value of monitoring duodenal mucosal perfusion using photoplethysmography.

    PubMed

    Fink, Mitchell P

    2014-01-01

    Photoplethysmography (PPG) is a technique that permits noninvasive measurement of changes in the volume of tissues. A novel device uses PPG to assess changes in duodenal mucosal perfusion. When tested in septic piglets, data obtained using this device correlate with the blood lactate concentration and duodenal serosal microvascular blood flow as measured with a laser Doppler flowmeter. This new PPG-based approach for continuously monitoring gut mucosal perfusion warrants further development, leading to prospective clinical trials in patients. PMID:25672458

  7. [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-Gurin (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

  8. Ileal Loop Fluid Accumulation and Production of Diarrhea in Rabbits by Cell-free Products of Clostridium perfringens1

    PubMed Central

    Duncan, Charles L.; Strong, Dorothy H.

    1969-01-01

    The ability of cell extracts and culture filtrates of various strains of C. perfringens to produce ileal loop fluid accumulation and overt diarrhea in rabbits was tested. Good correlation was obtained in the ability of whole cells and a toxic factor (present in cell extracts and concentrated culture filtrates) to produce both fluid accumulation in ileal loops and diarrhea when injected into the normal ileum of the rabbit. The toxic factor was present in cell-free preparations when cells were grown in a sporulation medium, but not when they were grown in an asporogenic medium. The factor was shown to be heat labile, nondialyzable, and was inactivated by Pronase but not by trypsin, lipase, or amylase. Loss of activity occurred at pH 1.0, 3.0, 5.0, and 12.0. PMID:4310083

  9. Glutathione activates virulence gene expression of an intracellular pathogen

    PubMed Central

    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

  10. Humoral and mucosal defense molecules rhythmically oscillate during a light-dark cycle in permit, Trachinotus falcatus.

    PubMed

    Lazado, Carlo C; Lund, Ivar; Pedersen, Per Bovbjerg; Nguyen, Huy Quang

    2015-12-01

    Circadian rhythm provides organisms with an internal system to maintain temporal order in a dynamic environment. This is typified by a 24-hcycle for a number of physiological processes, including immunity. The present study characterized the humoral and mucosal defense molecules and their dynamics during a light-dark (LD) cycle in juvenile permit, Trachinotus falcatus. All studied defense molecules were constitutively identified in serum and skin mucus. Serum generally exhibited higher levels of these defenses than skin mucus, with the exception of anti-protease (ANTIPRO). The difference in ANTIPRO, lysozyme (LYZ), esterase (ESA) and catalase (CAT) levels between serum and skin mucus was not affected by the phase of the daily cycle. However, a clear phase-dependent difference was observed in protease (PRO), globulin (GLOB), myeloperoxidase (MPO), alkaline phosphatase (ALP) and glutathione peroxidase (GPX) levels. Activities of ALP and GPX displayed significant daily rhythmicity in both serum and skin mucus. Circadian profile of ALP was identical in both biofluids, but an antiphasic feature was exhibited by GPX. GLOB and MPO levels also exhibited significant daily oscillation but only in serum with acrophases registered at ZT 14.5 and 6.15, respectively. Mucus PRO and serum ANTIPRO demonstrated significant temporal variations during a daily cycle albeit not rhythmic. Cluster analysis of the defense molecules in serum and skin mucus revealed two different daily profiles suggesting a possibility of distinct circadian control between humoral and mucosal immunity. These observations indicate that LD cycle had a remarkable impact in the defense molecules characterizing the humoral and mucosal immunity in permit. Daily rhythmic patterns of these defense molecules contribute to our understanding of the barely explored interplay of immunity and circadian rhythm in teleost fish. Lastly, the results could be useful in developing aquaculture practices aiming at modifying the immune functions of permit for improved health. PMID:26518503

  11. Nanocarriers for systemic and mucosal vaccine delivery.

    PubMed

    Shahiwala, Aliasgar; Vyas, Tushar K; Amiji, Mansoor M

    2007-01-01

    Over the past several years, immunization and treatment of infectious diseases has undergone a paradigm shift. Stemming from the vaccine research and development, not only a large number of disease-specific vaccines have been developed, but also enormous efforts have been made to improve the effectiveness of vaccines in order to provide optimal immunization. Introduction of nanotechnology and the development of nanocarrier-based vaccines have started to receive a lot of attention in order to provide effective immunization through better targeting and by triggering antibody response at the cellular level. Also, in the past several years, attention is placed on routes of vaccine administration in order to induce both mucosal and systemic immunity against the pathogen. Through judicious selection of the nanocarrier systems and the vaccine antigen, an optimal immunization and protection can be induced. This review article focuses on the patented applications of nanocarrier-based vaccine formulations and delivery. We have examined the United States patent literature to select inventions that specifically address this strategic approach for prevention of infectious diseases. PMID:19075870

  12. Gastric mucosal mast cells in atopic subjects.

    PubMed

    Bagnato, G F; Di Cesare, E; Caruso, R A; Gulli, S; Cugliari, A; Morabito Lo Prete, A; Previti, M; Muscar, M; Bottari, M

    1995-04-01

    Intragastral allergen provocation under endoscopic control (IPEC) allows direct observation of gastric mucosa reactions after contact with inhalant allergens that reach the stomach. We selected patients with proved atopy to Parietaria but without clinical and endoscopic signs of gastric disease, and we tested them with the specific inhalant allergen during IPEC, recording gastric macroscopic reaction and mucosal mast-cell changes in biopsy specimens. All atopic patients showed visible changes in gastric mucosa quantified as IPEC score. Mast-cell numbers detected in atopic patients (135.4 +/- 102.6/mm2 of stromal area) were significantly higher than in nonatopic subjects (59.8 +/- 25.4/mm2; P < 0.03) and were positively correlated to atopic IPEC score (P < 0.01). In addition, 6/12 atopics who had both higher mast-cell counts and IPEC score showed an intraepithelial distribution of gastric mast cells which displayed ultrastructural features of partial degranulation. It is likely that changes observed in our patients with allergy to Parietaria reflect a subclinical activation of mast cells in the gastric mucosa. PMID:7573815

  13. Mucosal Inflammatory Response to Salmonella typhimurium Infection

    PubMed Central

    Patel, Samir; McCormick, Beth A.

    2014-01-01

    The human intestinal epithelium consists of a single layer of epithelial cells that forms a barrier against food antigens and the resident microbiota within the lumen. This delicately balanced organ functions in a highly sophisticated manner to uphold the fidelity of the intestinal epithelium and to eliminate pathogenic microorganisms. On the luminal side, this barrier is fortified by a thick mucus layer, and on the serosal side exists the lamina propria containing a resident population of immune cells. Pathogens that are able to breach this barrier disrupt the healthy epithelial lining by interfering with the regulatory mechanisms that govern the normal balance of intestinal architecture and function. This disruption results in a coordinated innate immune response deployed to eliminate the intruder that includes the release of antimicrobial peptides, activation of pattern-recognition receptors, and recruitment of a variety of immune cells. In the case of Salmonella enterica serovar typhimurium (S. typhimurium) infection, induction of an inflammatory response has been linked to its virulence mechanism, the type III secretion system (T3SS). The T3SS secretes protein effectors that exploit the host’s cell biology to facilitate bacterial entry and intracellular survival, and to modulate the host immune response. As the role of the intestinal epithelium in initiating an immune response has been increasingly realized, this review will highlight recent research that details progress made in understanding mechanisms underlying the mucosal inflammatory response to Salmonella infection, and how such inflammatory responses impact pathogenic fitness of this organism. PMID:25071772

  14. Cystic fibrosis: a mucosal immunodeficiency syndrome

    PubMed Central

    Cohen, Taylor Sitarik; Prince, Alice

    2013-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a channel that regulates the transport of ions and the movement of water across the epithelial barrier. Mutations in CFTR, which form the basis for the clinical manifestations of cystic fibrosis, affect the epithelial innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation that fails to eradicate pulmonary pathogens. Compounding the effects of excessive neutrophil recruitment, the mutant CFTR channel does not transport antioxidants to counteract neutrophil-associated oxidative stress. Whereas mutant CFTR expression in leukocytes outside of the lung does not markedly impair their function, the expected regulation of inflammation in the airways is clearly deficient in cystic fibrosis. The resulting bacterial infections, which are caused by organisms that have substantial genetic and metabolic flexibility, can resist multiple classes of antibiotics and evade phagocytic clearance. The development of animal models that approximate the human pulmonary phenotypesairway inflammation and spontaneous infectionmay provide the much-needed tools to establish how CFTR regulates mucosal immunity and to test directly the effect of pharmacologic potentiation and correction of mutant CFTR function on bacterial clearance. PMID:22481418

  15. 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.

  16. Surface modified nanoparticulate carrier constructs for oral mucosal vaccine delivery.

    PubMed

    Mishra, Neeraj; Singh, Devendra; Sharma, Sandeep; Baldi, Ashish

    2014-01-01

    Mucosal administration of vaccines is one of the most popular approaches to induce desired immunity against various types of antigen and microbial in central as well as peripheral blood and in most external mucosal surfaces. The oral route is a preferred choice over parenteral route for this purpose mainly due to an ease of administration and therefore, for the possibility of covering large population for mass immunization. Different strategies of mucosal vaccination aimed to prevent colony formation and infection by pathogens and block its development. But a major concern with these vaccines is the degradation of protein components in stomach due to physiological conditions and gastric enzymes. Therefore, surface modified nanoparticles offer a better and stable alternative for efficient delivery and better activation of required immune responses. Natural and synthetic polymers are used to prepare nanoparticulate carrier systems for the development of oral mucosal vaccines. Amongst these, biodegradable polymers based nano-particulate carriers have been explored extensively for the development of delivery systems. Present review summarizes possible approaches and mechanisms for the systemic immunization by oral vaccines and critically discusses various polymers used, different strategies of surface modification to achieve targeting of antigen loaded nanoparticulate carrier at cellular level that are essentially required for a successful mucosal vaccination approach, and future prospects of nanoparticulate system as adjutants in oral mucosal vaccination. PMID:25007830

  17. Inside the brachycephalic nose: intranasal mucosal contact points.

    PubMed

    Schuenemann, Riccarda; Oechtering, Gerhard U

    2014-01-01

    The purpose of this study was to evaluate the prevalence of intranasal mucosal contact points in brachycephalic and normocephalic dogs. In total, 82 brachycephalic dogs (42 pugs and 40 French bulldogs) were evaluated by rhinoscopy for their intranasal mucosal contact and 25 normocephalic dogs were evaluated as a control group. Of those, 162 brachycephalic nasal cavities were evaluable and 140 had contact between intranasal structures (87%). Intraconchal and septoconchal mucosal contact points were the most commonly detected sites of contact. French bulldogs had a significantly higher prevalence of mucosal contact and had 3 mean contact points compared with 1.7 mean contact points per nasal cavity in pugs. Septal deviations were present in 62% of brachycephalic dogs. In the control group, mucosal contact points were present in only 7 of 50 nasal cavities (14%), and septal deviations occurred in 16% of those cases. Contact point average was 0.1 in large and 0.3 in small normocephalic dogs. Intranasal mucosal contact was identified as a common and previously unreported problem in brachycephalic dogs. Numerous contact points reduce the lumen of the intranasal passageways and indicate potential intranasal obstruction. Affected dogs might benefit from removal of obstructing conchae, potentially using laser-assisted turbinectomy. PMID:24659729

  18. A mucosal adjuvant for the inactivated poliovirus vaccine.

    PubMed

    Steil, Benjamin P; Jorquera, Patricia; Westdijk, Janny; Bakker, Wilfried A M; Johnston, Robert E; Barro, Mario

    2014-01-23

    The eradication of poliovirus from the majority of the world has been achieved through the use of two vaccines: the inactivated poliovirus vaccine (IPV) and the live-attenuated oral poliovirus vaccine (OPV). Both vaccines are effective at preventing paralytic poliomyelitis, however, they also have significant differences. Most importantly for this work is the risk of revertant virus from OPV, the greater cost of IPV, and the low mucosal immunity induced by IPV. We and others have previously described the use of an alphavirus-based adjuvant that can induce a mucosal immune response to a co-administered antigen even when delivered at a non-mucosal site. In this report, we describe the use of an alphavirus-based adjuvant (GVI3000) with IPV. The IPV-GVI3000 vaccine significantly increased systemic IgG, mucosal IgG and mucosal IgA antibody responses to all three poliovirus serotypes in mice even when administered intramuscularly. Furthermore, GVI3000 significantly increased the potency of IPV in rat potency tests as measured by poliovirus neutralizing antibodies in serum. Thus, an IPV-GVI3000 vaccine would reduce the dose of IPV needed and provide significantly improved mucosal immunity. This vaccine could be an effective tool to use in the poliovirus eradication campaign without risking the re-introduction of revertant poliovirus derived from OPV. PMID:24333345

  19. A Mucosal Adjuvant for the Inactivated Poliovirus Vaccine

    PubMed Central

    Steil, Benjamin P.; Jorquera, Patricia; Westdijk, Janny; Bakker, Wilfried A.M.; Johnston, Robert E.; Barro, Mario

    2014-01-01

    The eradication of poliovirus from the majority of the world has been achieved through the use of two vaccines: the inactivated poliovirus vaccine (IPV) and the live-attenuated oral poliovirus vaccine (OPV). Both vaccines are effective at preventing paralytic poliomyelitis, however, they also have significant differences. Most importantly for this work is the risk of revertant virus from OPV, the greater cost of IPV, and the low mucosal immunity induced by IPV. We and others have previously described the use of an alphavirus-based adjuvant that can induce a mucosal immune response to a co-administered antigen even when delivered at a non-mucosal site. In this report, we describe the use of an alphavirus-based adjuvant (GVI3000) with IPV. The IPV-GVI3000 vaccine significantly increased systemic IgG, mucosal IgG and mucosal IgA antibody responses to all three poliovirus serotypes in mice even when administered intramuscularly. Furthermore, GVI3000 significantly increased the potency of IPV in rat potency tests as measured by poliovirus neutralizing antibodies in serum. Thus, an IPV-GVI3000 vaccine would reduce the dose of IPV needed and provide significantly improved mucosal immunity. This vaccine could be an effective tool to use in the poliovirus eradication campaign without risking the re-introduction of revertant poliovirus derived from OPV. PMID:24333345

  20. Sodium alginate inhibits methotrexate-induced gastrointestinal mucositis in rats.

    PubMed

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

    2013-01-01

    Gastrointestinal mucositis is one of the most prevalent side effects of chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. Through its effects on normal tissues with high rates of proliferation, methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate-induced gastrointestinal mucositis is histologically characterized by crypt loss, callus fusion and atrophy, capillary dilatation, and infiltration of mixed inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is derived from seaweed and has demonstrated muco-protective and hemostatic effects on upper gastrointestinal ulcers. In the present study, we evaluated the effects of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for 3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h after methotrexate administration. On the 4th day, small intestines were removed and weighed. Subsequently, tissues were stained with hematoxylin-eosin and bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell numbers, hemoglobin levels, and hematocrit levels. These results suggest the potential of AL-Na as a therapy for methotrexate-induced small intestinal mucositis. PMID:24088251

  1. Ileal digestibility and endogenous flow of minerals and amino acids: responses to dietary phytic acid in piglets.

    PubMed

    Woyengo, Tofuko A; Cowieson, Aaron J; Adeola, Olayiwola; Nyachoti, Charles M

    2009-08-01

    Effects of phytic acid (PA) on ileal mineral and amino acid (AA) digestibilities and ileal endogenous AA flow in piglets were investigated. Seven ileal-cannulated weanling pigs were fed a casein-maize starch-based diet with PA (as sodium phytate) at 0, 5, 10 or 20 g/kg in 4 x 4 Latin square design with three added columns to give seven observations per treatment. The basal diet was formulated to meet National Research Council energy and AA requirements for piglets. The respective digestibility and endogenous lysine loss were determined by indicator and homoarginine methods. The apparent ileal digestibility (AID) of Na, K and P was linearly and quadratically reduced (P < 0.05) by increased dietary PA concentration, whereas that of Ca and Mg was only linearly reduced (P < 0.05) by the dietary PA. The AID values for Mg and Na were negative ( - 0.03 and - 0.18, respectively) when PA was supplemented at 20 g/kg. The AID of isoleucine, leucine and valine responded quadratically to dietary PA concentration, though the differences between the AID values of the AA due to change in dietary PA concentration were marginal (at most by 1.8 percentage units). Furthermore, dietary PA did not affect (P>0.05) endogenous AA losses. The results suggest that PA has limited effect on the digestibility and endogenous losses of AA in piglets, but can reduce AID of Mg and Na partly by increasing endogenous losses of these minerals as evidenced by their negative AID values. PMID:19144214

  2. Long-term Functional Results After Ileal Pouch Anal Restorative Proctocolectomy for Ulcerative Colitis

    PubMed Central

    Michelassi, Fabrizio; Lee, John; Rubin, Michele; Fichera, Alessandro; Kasza, Kristen; Karrison, Theodore; Hurst, Roger D.

    2003-01-01

    Objective: To document functional results in patients treated with an ileal pouch anal anastomosis (IPAA). Summary Background Data: The restorative proctocolectomy with IPAA has become the procedure of choice for patients with ulcerative colitis, yet the long-term functional results are not well known. Methods: We performed this prospective observational study in 391 consecutive patients (56% male; mean age, 33.7 10.8 years; range, 12-66 years) who underwent an IPAA between 1987 and 2002 (mean follow-up, 33.6 months; range, 0 to 180 months). Results: The majority of patients underwent the procedure under elective circumstances with a hand-sewn ileal pouch anal anastomosis and a protective ileostomy. In 25 patients (6.4%), the procedure was performed under urgent conditions; in 137 patients (35%), the temporary ileostomy was omitted; in 117 patients (29.9%), the ileal pouch anal anastomosis was stapled. There was 1 hospital mortality (0.25%) and 1 30-day mortality. Mean length of stay was 9.2 5.6 days (3-68 days; median, 8 days) and was increased by the occurrence of septic complications (8.9 versus 13.6 days; P < 0.02) and by the omission of a temporary ileostomy (8.3 versus 10.4 days; P = 0.005). Complications included pelvic abscess (1.3%), anastomotic dehiscence (6.4%), bowel obstruction (11.7%), and anastomotic stenosis in need of mechanical dilatation (10.7%). Patients were asked to record their functional results on a questionnaire for 1 week at 3, 6, 9, 12, 18, and 24 months after the IPAA and yearly thereafter. Our data to 10 years show that median number of bowel movements (bms) was 6 bm/24 hours at all time intervals. The average number of bms increased by 0.3 bm/decade of life (P < 0.001). Throughout the entire follow-up, more than 75% of patients had at least 1 bm most nights, although fewer than 40% found it necessary to alter the time of their meals to avoid bms at inappropriate times. Depending on the time interval, between 57% and 78% of patients were always able to postpone a bm until convenient, and this ability was similar in patients with a stapled or hand-sewn ileoanal anastomosis; only up to 18% were able to always distinguish between flatus and stools, and this ability was similar in patients with a stapled or hand-sewn ileoanal anastomosis. Complete daytime and nighttime continence was achieved by 53-76% of patients depending on the time interval. The percentage of fully continent patients was higher following the stapled rather than the hand-sewn technique (P < 0.001), and this difference persisted over time. When patients experienced incontinence, its occurrence ameliorated over time (P < 0.001), and the occurrence of perianal rash and itching as well as the use of protective pads decreased over time (P < 0.008). At 5 years, patients judged quality of life as much better or better in 81.4% and overall satisfaction and overall adjustment as excellent or good in 96.3% and 97.5%, respectively. Conclusions: We conclude that the IPAA confers a good quality of life. The majority of patients are fully continent, have 6 bms/d on average, and can defer a bm until convenient. When present, incontinence improves over time. PMID:14501509

  3. 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.

  4. Local bacteriophage isolates showed anti- Escherichia coli O157:H7 potency in an experimental ligated rabbit ileal loop model.

    PubMed

    Alam, Muntasir; Akhter, Marufa Zerin; Yasmin, Mahmuda; Ahsan, Chowdhury Rafiqul; Nessa, Jamalun

    2011-05-01

    Escherichia coli O157:H7 is considered among the most important recently emerged food-borne bacteria causing severe hemorrhagic diarrhea. Antibiotic treatment is not recommended as a prospective curative agent against this pathogen. Therefore, potency assessment of the local lytic phage isolates infecting E. coli O157:H7 as an alternate remedy to antibiotics was the principal concern of this study. Phage isolates against E. coli O157:H7 were checked by polymerase chain reaction for the presence of the virulence genes stx1 and stx2, and the safe phages were further screened in vitro for their capacity as biocontrol agents. Two bacteriophage strains, namely PAH6 and P2BH2, that had expressed potential antibacterial activity (P< 0.05) in vitro were selected for in vivo testing in ligated rabbit ileal loop models. Both phage isolates were capable of decreasing fluid accumulation in rabbit ileal loops along with reducing bacterial growth (r = 0.992). Combined application of the phages was found most satisfactory, reducing sevenlog cycles of bacterial growth. Consistent results in both in vivo and in vitro experiments demonstrate the applicability of bacteriophages as a rapid response tool against E.coli O157:H7. To our knowledge, this is the first successful application of the rabbit ileal loop test for therapeutic evaluation of bacteriophages. PMID:21542784

  5. A new drug delivery system targeting ileal epithelial cells induced electrogenic sodium absorption: possible promotion of intestinal adaptation.

    PubMed

    Haneda, Sho; Fukushima, Kouhei; Funayama, Yuji; Shibata, Chikashi; Takahashi, Ken-Ichi; Tabata, Yasuhiko; Sasaki, Iwao

    2007-05-01

    We previously demonstrated the induction of the epithelial sodium channel, prostasin, and 11beta-hydroxysteroid dehydrogenase type 2 and activation of sodium transport mediated by those molecules in the remnant ileum after total proctocolectomy. The aims of the present study were to develop a new drug delivery system that targets ileal epithelial cells and to enhance local mineralocorticoid action without systemic effects. Orally administered D-aldosterone-containing D,L-lactide/glycolide acid copolymer microspheres are absorbed in the rat terminal ileum and released aldosterone. Blood and terminal ileal tissues were collected 2 weeks after the administration of the microspheres, and the aldosterone concentrations, mRNA, and protein expressions of the above molecules and sodium transport were evaluated. Significantly high levels of tissue aldosterone in the absence of elevated plasma levels were detected in the microspheres-treated rats. Epithelial mRNA and protein expression of the above molecules increased significantly in the microspheres-treated animals. Electrogenic sodium transport in the ileum was enhanced in the microspheres-treated rats. Aldosterone-containing microspheres successfully induced the expression of the above molecules and activated sodium transport in the ileal mucosa, both of which are essential for intestinal adaptation. Pre- and/or postoperative treatment with this drug may compensate for the excessive loss of sodium and water following proctocolectomy. PMID:17468916

  6. Combining gastric and ileal segments, does it overcome segment-related complications? An experimental study on rats.

    PubMed

    Burgu, Berk; Gkce, Mehmet ?lker; Aydo?du, zg; Ser, Evren; Kankaya, Duygu; Soygr, Tarkan

    2011-02-01

    Bladder augmentation has revolutionized the care of children with neurogenic bladder but it is associated with certain short- and long-term complications. Using the combination of gastric and ileal segments to balance effects of these segments might be a solution for complications. A total of 39 female Spraque-Dawley rats randomly divided into four groups: ileocystoplasty (11), gastrocystoplasty (9), ileogastrocystoplasty (11) and control (8). Serum/urine electrolytes and pH values, and serum creatinine levels and urine mucus concentration were measured. Kruskal-Wallis non-parametric variance analysis was performed to compare the groups and p < 0.05 was accepted as significant. Metabolic alkalosis with significantly lower urine pH was observed in gastrocystoplasty group. Gastroileal group showed similar results with the ileal group in all parameters. No stone formation was detected in the sham and gastric cystoplasty groups. Metaplastic and hyperplastic changes were observed in all segments surrounding urothelium. In conclusion, combination of gastric and ileal segments does not significantly reduce the rate of metabolic impairments, stone and mucus formation. Besides it is not associated with significant improvement in histological outcome since urine is still in contact with the gastrointestinal mucosa. PMID:20556373

  7. Gata4 is essential for the maintenance of jejunal-ileal identities in the adult mouse small intestine.

    PubMed

    Bosse, Tjalling; Piaseckyj, Christina M; Burghard, Ellen; Fialkovich, John J; Rajagopal, Satish; Pu, William T; Krasinski, Stephen D

    2006-12-01

    Gata4, a member of the zinc finger family of GATA transcription factors, is highly expressed in duodenum and jejunum but is nearly undetectable in distal ileum of adult mice. We show here that the caudal reduction of Gata4 is conserved in humans. To test the hypothesis that the regional expression of Gata4 is critical for the maintenance of jejunal-ileal homeostasis in the adult small intestine in vivo, we established an inducible, intestine-specific model that results in the synthesis of a transcriptionally inactive Gata4 mutant. Synthesis of mutant Gata4 in jejuna of 6- to 8-week-old mice resulted in an attenuation of absorptive enterocyte genes normally expressed in jejunum but not in ileum, including those for the anticipated targets liver fatty acid binding protein (Fabp1) and lactase-phlorizin hydrolase (LPH), and a surprising induction of genes normally silent in jejunum but highly expressed in ileum, specifically those involved in bile acid transport. Inactivation of Gata4 resulted in an increase in the goblet cell population and a redistribution of the enteroendocrine subpopulations, all toward an ileal phenotype. The gene encoding Math1, a known activator of the secretory cell fate, was induced approximately 75% (P < 0.05). Gata4 is thus an important positional signal required for the maintenance of jejunal-ileal identities in the adult mouse small intestine. PMID:16940177

  8. 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

  9. Glutathione and modulation of cell apoptosis

    PubMed Central

    Circu, Magdalena L.; Aw, Tak Yee

    2012-01-01

    Apoptosis is a highly organized form of cell death that is important for tissue homeostasis, organ development and senescence. To date, the extrinsic (death receptor mediated) and intrinsic (mitochondria derived) apoptotic pathways have been characterized in mammalian cells. Reduced glutathione, GSH, is the most prevalent cellular thiol that plays an essential role in preserving a reduced intracellular environment. GSH protection of cellular macromolecules like DNA, proteins and lipids against oxidizing, environmental and cytotoxic agents, underscores its central anti-apoptotic function. Reactive oxygen and nitrogen species (ROS/RNS) can oxidize cellular GSH or induce its extracellular export leading to the loss of intracellular redox homeostasis and activation of the apoptotic signaling cascade. Recent evidence uncovered a novel role for GSH involvement in apoptotic signaling pathways wherein post-translational S-glutathiolation of protein redox active cysteines is implicated in the potentiation of apoptosis. In the present review we focus on the key aspects of GSH redox mechanisms associated with apoptotic signaling that includes: (a) changes in cellular GSH redox homeostasis through GSH oxidation or GSH transport in relation to the initiation or propagation of the apoptotic cascade, and (b) evidence for S-glutathiolation in protein modulation and apoptotic initiation. PMID:22732297

  10. The Genetic Architecture of Murine Glutathione Transferases

    PubMed Central

    Lu, Lu; Pandey, Ashutosh K.; Houseal, M. Trevor; Mulligan, Megan K.

    2016-01-01

    Glutathione S-transferase (GST) genes play a protective role against oxidative stress and may influence disease risk and drug pharmacokinetics. In this study, massive multiscalar trait profiling across a large population of mice derived from a cross between C57BL/6J (B6) and DBA2/J (D2)—the BXD family—was combined with linkage and bioinformatic analyses to characterize mechanisms controlling GST expression and to identify downstream consequences of this variation. Similar to humans, mice show a wide range in expression of GST family members. Variation in the expression of Gsta4, Gstt2, Gstz1, Gsto1, and Mgst3 is modulated by local expression QTLs (eQTLs) in several tissues. Higher expression of Gsto1 in brain and liver of BXD strains is strongly associated (P < 0.01) with inheritance of the B6 parental allele whereas higher expression of Gsta4 and Mgst3 in brain and liver, and Gstt2 and Gstz1 in brain is strongly associated with inheritance of the D2 parental allele. Allele-specific assays confirmed that expression of Gsto1, Gsta4, and Mgst3 are modulated by sequence variants within or near each gene locus. We exploited this endogenous variation to identify coexpression networks and downstream targets in mouse and human. Through a combined systems genetics approach, we provide new insight into the biological role of naturally occurring variants in GST genes. PMID:26829228

  11. Mucosal immunization using proteoliposome and cochleate structures from Neisseria meningitidis serogroup B induce mucosal and systemic responses.

    PubMed

    Campo, Judith Del; Zayas, Caridad; Romeu, Belkis; Acevedo, Reinaldo; González, Elizabeth; Bracho, Gustavo; Cuello, Maribel; Cabrera, Osmir; Balboa, Julio; Lastre, Miriam

    2009-12-01

    Most pathogens either invade the body or establish infection in mucosal tissues and represent an enormous challenge for vaccine development by the absence of good mucosal adjuvants. A proteoliposome-derived adjuvant from Neisseria meningitidis serogroup B (AFPL1, Adjuvant Finlay Proteoliposome 1) and its derived cochleate form (Co, AFCo1) contain multiple pathogen-associated molecular patterns as immunopotentiators, and can also serve as delivery systems to elicit a Th1-type immune response. The present studies demonstrate the ability of AFPL1and AFCo1 to induce mucosal and systemic immune responses by different mucosal immunizations routes and significant adjuvant activity for antibody responses of both structures: a microparticle and a nanoparticle with a heterologous antigen. Therefore, we used female mice immunized by intragastric, intravaginal, intranasal or intramuscular routes with both structures alone or incorporated with ovalbumin (OVA). High levels of specific IgG antibody were detected in all sera and in vaginal washes, but specific IgA antibody in external secretions was only detected in mucosally immunized mice. Furthermore, antigen specific IgG1 and IgG2a isotypes were all induced. AFPL1 and AFCo1 are capable of inducing IFN-gamma responses, and chemokine secretions, like MIP-1alpha and MIP-1beta. However, AFCo1 is a better alternative to induce immune responses at mucosal level. Even when we use a heterologous antigen, the AFCo1 response was better than with AFPL1 in inducing mucosal and systemic immune responses. These results support the use of AFCo1 as a potent Th1 inducing adjuvant particularly suitable for mucosal immunization. PMID:19410000

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

    PubMed

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

    2006-04-01

    Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was studied for its antiulcer and mucosal defensive factors in normal and non-insulin dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing blood glucose level >140mg/dL after 12 weeks of STZ administration were considered as NIDDM positive. Effects of MSE were compared with known ulcer protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent changes in gastric mucosal glycoproteins, cell proliferation, free radicals (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU. NIDDM caused a significant decrease in gastric mucosal glycoprotein level without having any effect on cell proliferation. However, all the test drugs reversed the decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further increase in LPO and NO level without causing any further changes in SOD and CAT level. MSE pretreatment showed reversal in the levels of all the above parameters better than GLC. Ethanol caused a decrease in glutathione level which was further reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats. However, SFT was ineffective in reversing the changes induced by CRS or ethanol or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the ulcer protective effect of MSE could be due to its predominant effect on mucosal glycoprotein, cell proliferation, free radicals and antioxidant systems. PMID:16629371

  13. Xylanase increased the ileal digestibility of nonstarch polysaccharides and concentration of low molecular weight nondigestible carbohydrates in pigs fed high levels of wheat distillers dried grains with solubles.

    PubMed

    Pedersen, M B; Yu, S; Arent, S; Dalsgaard, S; Bach Knudsen, K E; Lrke, H N

    2015-06-01

    The objective was to study the effect of a commercially available xylanase (CAX), an experimental xylanase (EX), and EX in combination with protease (EXP) on the degradation of nondigestible carbohydrates (NDC) and apparent ileal digestibility (AID) of nutrients in wheat distillers dried grains with solubles (wDDGS). The control and 3 enzyme diets contained 96% wDDGS supplemented with vitamins, minerals, L-lysine, and chromic oxide as a digestibility marker in addition to enzyme premix. Eight ileal cannulated pigs were fed 4 experimental diets containing 96% wDDGS-a control diet or 1 of 3 diets with CAX, EX, or EXP-in a double 4 4 Latin square design. The experimental period lasted 7 d; adaptation lasted 4 d, and the ileal digesta were collected for 8 h on d 5 and 7, when spot samples of feces were also collected. Digesta samples were analyzed for NDC, total and soluble nonstarch polysaccharides (NSP), low molecular weight (LMW) NDC, OM, CP, fat, starch, and marker. Compared with the control diet, addition of CAX, EX, and EXP increased the AID of arabinoxylan by 32 (P < 0.001), 28 (P = 0.001), and 24% (P = 0.004), respectively. In addition, EXP increased the AID of noncellulosic polysaccharide glucose by 21% compared with the control (P = 0.005). Compared with the control, addition of EX, EXP, and CAX decreased the concentration of soluble arabinoxylan in ileal digesta by 40 (P < 0.0001), 40 (P < 0.0001), and 21% (P = 0.022), respectively. Furthermore, addition of CAX, EXP, and EX increased the concentration of LMW arabinoxylan in ileal digesta by 40 (P = 0.0001), 36 (P = 0.0006), and 24% (P = 0.023), respectively, compared with the control. Addition of EX and EXP decreased the concentration of soluble NSP of ileal digesta by 25 (P = 0.001) and 26% (P < 0.001), respectively, compared with the control diet. Addition of CAX (P < 0.0001) and EXP (P = 0.013) increased the arabinose-to-xylose ratio in the insoluble arabinoxylan fraction in ileal digesta compared with the control diet, and CAX increased the uronic acid-to-xylose ratio of the ileal insoluble NSP fraction (P < 0.0001) compared with the control diet. Enzyme addition did not affect AID of OM, CP, starch, and fat (P > 0.3). In conclusion, addition of xylanases to wDDGS diets increased the ileal digestibility of NSP and generated LMW NDC components in the small intestine of pigs but did not affect ileal digestibility of nutrients in the current study. PMID:26115275

  14. Phytase Modulates Ileal Microbiota and Enhances Growth Performance of the Broiler Chickens

    PubMed Central

    Ptak, Anna; Bedford, Michael R.; Świątkiewicz, Sylwester; Żyła, 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

  15. Performance and ileal histomorphology of rats treated with humic acid preparations.

    PubMed

    Yasar, S; Gokcimen, A; Altuntas, I; Yonden, Z; Petekkaya, E

    2002-08-01

    As humic acid (HA) substances have antiphlogistic, adsorptive, antitoxic and antimicrobial properties, we studied the possible effects of Farmaglatr, an organic HA preparation, on the rat performance, nutrient retention, ileal histomorphology and hydroxyproline (HP) content of the ileum in two experiments. In experiment 1, 48 male Wistar albino rats were allotted to three dietary treatments. Each was randomly assigned to four cages, each with four rats. The treatments consisted of a control diet (C) with no addition of Farmaglator Dry or Liquid, a treatment with addition of 2.5 g/kg Farmaglator Dry (FDry) and a control diet containing no FDry, but the rats had 3.5 ml/l Farmaglator Liquid in drinking water (FLiquid). The experiment lasted for 20 days. Changes in live weight were recorded at days 10 and 20 of the experiment. At the end of 20 days, all rats were killed to collect samples of intestinal tissues for the measurements of histological parameters. In experiment 2, 30 rats weaned at 21 days of age were divided into three groups, each with 10 rats, and individually caged in metabolism cages for 10 days. The above three treatments were randomly assigned to rats for 10 days to record body weight and feed intake. During the last 5 days, faecal outputs were collected to determine the dry matter and nitrogen retention. In experiment 1, FDry and FLiquid rats significantly (p<0.05) gained more live weight than the control rats. Improved weight gain with HA preparations was found to be highly associated with a high epithelial surface area as there were significantly (p<0.05) longer villi heights and crypt depths and increased HP contents of ileum in the HA treated rats compared with the control rats. Although the increased weight gain in FLiquid rats did not significantly (p>0.05) differ from the control rats in experiment 2 in contrast to the result in experiment 1, the FDry rats significantly (p < 0.05) gained more weight than the control rats. This was primarily found to be associated with significantly (p<0.05) increased feed intake and nitrogen retention in FDry rats compared with the control rats. It can be concluded that HA preparations, especially FDry, caused increased weight gain in rats as overall of two experiments. The improved weight gain only by FDry preparation was associated with increased ileal epithelial mass, increased feed intake, improved feed : gain ratio and increased nitrogen retention in rats. PMID:15379912

  16. Ileal pouch-anal anastomoses complications and function in 1005 patients.

    PubMed Central

    Fazio, V W; Ziv, Y; Church, J M; Oakley, J R; Lavery, I C; Milsom, J W; Schroeder, T K

    1995-01-01

    BACKGROUND: Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) has become an established surgery for patients with chronic ulcerative colitis and familial adenomatous polyposis. PURPOSE: The authors report the results of an 11-year experience of restorative proctocolectomy and IPAA at a tertiary referral center. METHODS: Chart review was performed for 1005 patients undergoing IPAA from 1983 through 1993. Preoperative histopathologic diagnoses were ulcerative colitis (n = 858), familial adenomatous polyposis (n = 62), indeterminate colitis (n = 75), and miscellaneous (n = 10). Information was obtained regarding patient demographics, type and duration of diseases, previous operations, and indications for surgery. Data were collected on surgical procedure and postoperative pathologic diagnosis. Early (within 30 days after surgery) and late complications were noted. Follow-up included an annual function and quality-of-life questionnaire, physical examination, and biopsies of the pouch and anal transitional zone. RESULTS: Of the 1005 patients (455 women), postoperative histopathologic diagnoses were as follows: ulcerative colitis (n = 812), familial adenomatous polyposis (n = 62), indeterminate colitis (n = 54), Crohn's disease (n = 67), and miscellaneous (n = 10). During a mean follow-up time of 35 months (range 1-125 months), histopathologic diagnoses were changed for 25 patients. The overall mortality rate was 1% (n = 10 patients, early = 4, late = 6); one death (0.1%) was related to pouch necrosis and sepsis. The overall morbidity rate was 62.7% (1218 complications in 630 patients; early, n = 27.5%; late, n = 50.5%). Septic complication and reoperation rates were 6.8% and 24%, respectively. The ileal pouch was removed in 34 patients (3.4%), and it is nonfunctional in 11 (1%). Functional results and quality of life were good to excellent in 93% of the patients with complete data (n = 645) and are similar for patients with ulcerative colitis, familial adenomatous polyposis, indeterminate colitis, and Crohn's disease. Patients who underwent operations from 1983 through 1988 have similar functional results and quality of life compared with patients who underwent operations after 1988. CONCLUSION: Restorative proctocolectomy with an IPAA is a safe procedure, with low mortality and major morbidity rates. Although total morbidity rate is appreciable, functional results generally are good and patient satisfaction is high. PMID:7639579

  17. Phytase modulates ileal microbiota and enhances growth performance of the broiler chickens.

    PubMed

    Ptak, Anna; Bedford, Michael R; Świątkiewicz, Sylwester; Żyła, 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

  18. Quantitation of protein S-glutathionylation by liquid chromatography-tandem mass spectrometry: correction for contaminating glutathione and glutathione disulfide.

    PubMed

    Bukowski, Michael R; Bucklin, Christopher; Picklo, Matthew J

    2015-01-15

    Protein S-glutathionylation is a posttranslational modification that links oxidative stimuli to reversible changes in cellular function. Protein-glutathione mixed disulfide (PSSG) is commonly quantified by reduction of the disulfide and detection of the resultant glutathione species. This methodology is susceptible to contamination by free unreacted cellular glutathione (GSH) species, which are present in 1000-fold greater concentration. A liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method was developed for quantification of glutathione and glutathione disulfide (GSSG), which was used for the determination of PSSG in biological samples. Analysis of rat liver samples demonstrated that GSH and GSSG coprecipitated with proteins similar to the range for PSSG in the sample. The use of [(13)C2,(5)N]GSH and [(13)C4,(5)N2]GSSG validated these results and demonstrated that the release of GSH from PSSG did not occur during sample preparation and analysis. These data demonstrate that GSH and GSSG contamination must be accounted for when determining PSSG content in cellular/tissue preparations. A protocol for rinsing samples to remove the adventitious glutathione species is demonstrated. The fragmentation patterns for glutathione were determined by high-resolution mass spectrometry, and candidate ions for detection of PSSG on protein and protein fragments were identified. PMID:25448621

  19. 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, γ-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

  20. The content of glutathione and glutathione S-transferases and the glutathione peroxidase activity in rat liver nuclei determined by a non-aqueous technique of cell fractionation.

    PubMed Central

    Soboll, S; Grndel, S; Harris, J; Kolb-Bachofen, V; Ketterer, B; Sies, H

    1995-01-01

    Hepatocellular nuclei require glutathione, glutathione S-transferases (GSTs) and Se-dependent glutathione peroxidase (GPx) for intranuclear protection against damage from electrophiles or products of active oxygen. Data so far available from the literature on nuclei isolated in aqueous systems range from glutathione, GSTs and GPx either being absent altogether to being present in quantities in excess of those in the cytoplasm. This paper describes a small-scale preparation of a nuclear fraction from rat liver by a non-aqueous technique, designed to retain nuclear water-soluble molecules in situ, since low-molecular-mass compounds can diffuse freely into other compartments during aqueous separation. This non-aqueous procedure shows the nucleus to contain glutathione at 8.4 mM and soluble GSTs at 38 micrograms/mg of protein, the enrichment over the homogenate being 1.2-1.4-fold. Se-dependent GPx activity was also present in the nucleus (56 m-units/mg), although with slightly lower activity than in the homogenate (0.7-fold). Images Figure 1 PMID:7487946

  1. Chronic Arsenic Exposure and Blood Glutathione and Glutathione Disulfide Concentrations in Bangladeshi Adults

    PubMed Central

    Hall, Megan N.; Niedzwiecki, Megan; Liu, Xinhua; Harper, Kristin N.; Alam, Shafiul; Slavkovich, Vesna; Ilievski, Vesna; Levy, Diane; Siddique, Abu B.; Parvez, Faruque; Mey, Jacob L.; van Geen, Alexander; Graziano, Joseph

    2013-01-01

    Background: In vitro and rodent studies have shown that arsenic (As) exposure can deplete glutathione (GSH) and induce oxidative stress. GSH is the primary intracellular antioxidant; it donates an electron to reactive oxygen species, thus producing glutathione disulfide (GSSG). Cysteine (Cys) and cystine (CySS) are the predominant thiol/disulfide redox couple found in human plasma. Arsenic, GSH, and Cys are linked in several ways: a) GSH is synthesized via the transsulfuration pathway, and Cys is the rate-limiting substrate; b) intermediates of the methionine cycle regulate both the transsulfuration pathway and As methylation; c) GSH serves as the electron donor for reduction of arsenate to arsenite; and d) As has a high affinity for sulfhydryl groups and therefore binds to GSH and Cys. Objectives: We tested the hypothesis that As exposure is associated with decreases in GSH and Cys and increases in GSSG and CySS (i.e., a more oxidized environment). Methods: For this cross-sectional study, the Folate and Oxidative Stress Study, we recruited a total of 378 participants from each of five water As concentration categories: < 10 (n = 76), 10–100 (n = 104), 101–200 (n = 86), 201–300 (n = 67), and > 300 µg/L (n = 45). Concentrations of GSH, GSSG, Cys, and CySS were measured using HPLC. Results: An interquartile range (IQR) increase in water As was negatively associated with blood GSH (mean change, –25.4 µmol/L; 95% CI: –45.3, –5.31) and plasma CySS (mean change, –3.00 µmol/L; 95% CI: –4.61, –1.40). We observed similar associations with urine and blood As. There were no significant associations between As exposure and blood GSSG or plasma Cys. Conclusions: The observed associations are consistent with the hypothesis that As may influence concentrations of GSH and other nonprotein sulfhydryls through binding and irreversible loss in bile and/or possibly in urine. Citation: Hall MN, Niedzwiecki M, Liu X, Harper KN, Alam S, Slavkovich V, Ilievski V, Levy D, Siddique AB, Parvez F, Mey JL, van Geen A, Graziano J, Gamble MV. 2013. Chronic arsenic exposure and blood glutathione and glutathione disulfide concentrations in Bangladeshi adults. Environ Health Perspect 121:1068–1074; http://dx.doi.org/10.1289/ehp.1205727 PMID:23792557

  2. 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 β-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

  3. Hemoglobin-catalyzed fluorometric method for the determination of glutathione

    NASA Astrophysics Data System (ADS)

    Wang, Ruiqiang; Tang, Lin; Li, Hua; Wang, Yi; Gou, Rong; Guo, Yuanyuan; Fang, Yudong; Chen, Fengmei

    2016-01-01

    A new spectrofluorometric method for the determination of glutathione based on the reaction catalyzed by hemoglobin was reported. The reaction product gave a highly fluorescent intensity with the excitation and emission wavelengths of 320.0 nm and 413.0 nm, respectively. The optimum experimental conditions were investigated. Results showed that low concentration glutathione enhanced the fluorescence intensity significantly. The line ranges were 1.0 × 10-6-1.0 × 10-5 mol L-1 of glutathione and 6.0 × 10-10 mol L-1-1.0 × 10-8 mol L-1, respectively. The detection limit was calculated to be 1.1 × 10-11 mol L-1. The recovery test by the standard addition method gave values in the range of 90.78%-102.20%. This method was used for the determination of glutathione in synthetic and real samples with satisfactory results.

  4. Mucosal immunization using recombinant plant-based oral vaccines.

    PubMed

    Streatfield, Stephen J

    2006-02-01

    The induction of mucosal immunity is very important in conferring protection against pathogens that typically invade via mucosal surfaces. Delivery of a vaccine to a mucosal surface optimizes the induction of mucosal immunity. The apparent linked nature of the mucosal immune system allows delivery to any mucosal surface to potentially induce immunity at others. Oral administration is a very straightforward and inexpensive approach to deliver a vaccine to the mucosal lining of the gut. However, vaccines administered by this route are subject to proteolysis in the gastrointestinal tract. Thus, dose levels for protein subunit vaccines are likely to be very high and the antigen may need to be protected from proteolysis for oral delivery to be efficacious. Expression of candidate vaccine antigens in edible recombinant plant material offers an inexpensive means to deliver large doses of vaccines in encapsulated forms. Certain plant tissues can also stably store antigens for extensive periods of time at ambient temperatures, obviating the need for a cold-chain during vaccine storage and distribution, and so further limiting costs. Antigens can be expressed from transgenes stably incorporated into a host plant's nuclear or plastid genome, or from engineered plant viruses infected into plant tissues. Molecular approaches can serve to boost expression levels and target the expressed protein for appropriate post-translational modification. There is a wide range of options for processing plant tissues to allow for oral delivery of a palatable product. Alternatively, the expressed antigen can be enriched or purified prior to formulation in a tablet or capsule for oral delivery. Fusions to carrier molecules can stabilize the expressed antigen, aid in antigen enrichment or purification strategies, and facilitate delivery to effector sites in the gastrointestinal tract. Many antigens have been expressed in plants. In a few cases, vaccine candidates have entered into early phase clinical trials, and in the case of farmed animal vaccines into relevant animal trials. PMID:16431131

  5. 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

  6. Amodiaquine failure associated with erythrocytic glutathione in Plasmodium falciparum malaria

    PubMed Central

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

    2007-01-01

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

  7. 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

  8. Large bifid ureteric calculus in a patient with an ileal conduit

    PubMed Central

    Rajaian, Shanmugasundaram; Kekre, Nitin S.

    2012-01-01

    Urinary diversion after extirpative surgery of the bladder is done by various methods. Conduit urinary diversion is the most commonly practiced method of urinary diversion. It is relatively easy to perform and has a lower complication rate than other forms of diversion, e.g., orthotopic neobladder and continent cutaneous urinary diversion. Urolithiasis is a known and common complication of urinary diversion. Upper tract calculi in these cases often manifest symptomatically as occurs in the general population. Stones in the conduit can have a variable clinical presentation. Asymptomatic presentation is also noted in a few cases. We report a case of a large silent bifid ureteric calculus within an ileal conduit in a woman who had undergone urinary diversion 32 years earlier. Plain X-ray of the abdomen is the only investigation necessary to rule out urinary lithiasis in those who have had urinary diversion for a long time. This simple tool can diagnose the condition well in advance and aid in planning the management of this condition. PMID:23248527

  9. Green tea catechin EGCG inhibits ileal apical sodium bile acid transporter ASBT.

    PubMed

    Annaba, Fadi; Kumar, Pradeep; Dudeja, Amish K; Saksena, Seema; Gill, Ravinder K; Alrefai, Waddah A

    2010-03-01

    Green tea catechins exhibit hypocholesterolemic effects probably via their inhibitory effects on intestinal bile acid absorption. Ileal apical sodium-dependent bile acid transporter (ASBT) is responsible for reabsorption of bile acids. The present studies were, therefore, designed to investigate the modulation of ASBT function and membrane expression by green tea catechins in human embryonic kidney HEK-293 cells stably transfected with ASBT-V5 fusion protein and intestinal Caco-2 monolayers. Our data showed that ASBT activity was significantly decreased by (-)-epigallocatechin-3-gallate (EGCG) but not other green tea catechins. Inhibition of PKC, phosphatidylinositol 3-kinase, and MAPK-dependent pathways failed to block the reduction in ASBT activity by EGCG. Kinetics studies showed a significant decrease in the V(max) of the transporter, whereas total ASBT content on the plasma membrane was unaltered by EGCG. Concomitant with the decrease in ASBT function, EGCG significantly reduced ASBT pool in the detergent-insoluble fraction, while increasing its presence in the detergent-soluble fraction of plasma membrane. Furthermore, EGCG decreased the association of ASBT with floating lipid raft fractions of cellular membrane on Optiprep density gradient. In conclusion, our data demonstrate a novel role of lipid rafts in the modulation of ASBT function by the dietary component EGCG, which may underlie the hypocholesterolemic effects of green tea. PMID:20056894

  10. Inhibitory effect of ginger (Zingiber officinale) on rat ileal motility in vitro.

    PubMed

    Borrelli, Francesca; Capasso, Raffaele; Pinto, Aldo; Izzo, Angelo A

    2004-04-23

    Ginger (Zingiber officinale rhizome) is a widespread herbal medicine mainly used for the treatment of gastrointestinal diseases, including dyspepsia, nausea and diarrhoea. In the present study we evaluated the effect of this herbal remedy on the contractions induced by electrical stimulation (EFS) or acetylcholine in the isolated rat ileum. Ginger (0.01-1000 microg/ml) inhibited both EFS- and acetylcholine-evoked contractions, being more potent in inhibiting the contractions induced by EFS. The depressant effect of ginger on EFS-induced contractions was reduced by the vanilloid receptor antagonist capsazepine (10(-5) M), but unaffected by the alpha(2)-adrenergic antagonist yohimbine (10(-7) M), the CB(1) receptor antagonist SR141716A (10(-6) M), the opioid antagonist naloxone (10(-6) M) or by the NO synthase inhibitor L-NAME (3 x 10(-4) M). Zingerone (up to 3 x 10(-4) M), one of the active ingredients of ginger, did not possess inhibitory effects. It is concluded that ginger possesses both prejunctional and postjunctional inhibitory effects on ileal contractility; the prejunctional inhibitory effect of ginger on enteric excitatory transmission could involve a capsazepine-sensible site (possibly vanilloid receptors). PMID:15050426

  11. Ileal Intussusception Due to Metastasis from Squamous Cell Carcinoma of the Lung Resected 12 Years Previously.

    PubMed

    Nakamura, Tomoki; Chino, Osamu; Tajima, Takayuki; Tanaka, Yoichi; Yokoyama, Daiki; Hanashi, Tomoko; Sadahiro, Sotaro; Makuuchi, Hiroyasu

    2015-01-01

    An 88-year-old woman, with a history of resection of stage IIA lung cancer in 1998, was referred to our hospital in August 2010 complaining of upper abdominal pain, vomiting, and dark brown stools. After endoscopic examination, she was admitted with a diagnosis of Mallory-Weiss syndrome. Vomiting ecurred when food intake was resumed after fasting. Intestinal obstruction was suspected on abdominal radiography, and complete small bowel obstruction was confirmed by contrast-enhanced imaging after placement of an ileus tube. A small intestinal tumor with intussusception was detected by computed tomography. At laparotomy, there was no ascites. Intussusception was found due to an ileal tumor located approximately 50 cm from the ileocecal valve, and we performed partial small bowel resection. The resected small intestine contained a submucosal tumor approximately 40 mm in diameter that had penetrated the bowel wall to reach the serosa. Pathological examination revealed a submucosal tumor that showed poor continuity with the surrounding mucosa, while the histology was squamous cell carcinoma. Immunohistochemistry showed that the tumor was CK7 positive, CK20 negative, TTF-1 negative, and CK10 positive. Based on these findings, we made a diagnosis of small intestinal metastasis at 12 years after radical resection of squamous cell carcinoma of the lung. PMID:26662663

  12. Inhibition of rat liver microsomal NADPH cytochrome P450 reductase by glutathione and glutathione disulfide.

    PubMed

    Scholz, R W; Reddy, P V; Liken, A D; Reddy, C C

    1996-09-13

    Previously we have demonstrated inhibition of lipid peroxidation by reduced glutathione (GSH) in rat liver microsomes that is dependent upon the presence of alpha-tocopheral (alpha-TH) in the membranes. Glutathione disulfide (GSSG) potentiated the inhibitory effect of GSH in an enzymatic (NADPH-dependent) lipid peroxidation system in rat liver microsomes; however, inhibition by GSH + GSSG is independent of alpha-TH. When we repeated these experiments with a non-enzymatic system (ascorbate/ADP) to stimulate lipid peroxidation, GSSG did not potentiate the inhibitory effect of GSH. To delineate the mechanism of inhibition of microsomal lipid peroxidation by GSH + GSSG, we examined the effects of these compounds on cytochrome P-450 reductase (EC 1.6.2.4), an important component of the NADPH-dependent enzymatic lipid peroxidation system. It was observed that GSH alone caused about 25% and 21% inhibition of reductase activity in crude microsomes and partially purified enzyme preparations, respectively. There was no inhibition of reductase activity by GSSG alone in either crude microsomes or partially purified enzyme preparations. However, when added together, GSH and GSSG enhanced the inhibition of reductase activity in crude microsomes and partially purified enzyme by 39% and 56%, respectively. We speculate that one possible mechanism for the inhibition of NADPH-dependent lipid peroxidation by GSH + GSSG is, in part, due to inhibition of NADPH cytochrome P-450 reductase, thus affecting the initiation phase of lipid peroxidation. PMID:8806659

  13. Allyl isothiocyanate depletes glutathione and upregulates expression of glutathione S-transferases in Arabidopsis thaliana

    PubMed Central

    verby, Anders; Stokland, Ragni A.; sberg, Signe E.; Sporsheim, Bjrnar; Bones, Atle M.

    2015-01-01

    Allyl isothiocyanate (AITC) is a phytochemical associated with plant defense in plants from the Brassicaceae family. AITC has long been recognized as a countermeasure against external threats, but recent reports suggest that AITC is also involved in the onset of defense-related mechanisms such as the regulation of stomatal aperture. However, the underlying cellular modes of action in plants remain scarcely investigated. Here we report evidence of an AITC-induced depletion of glutathione (GSH) and the effect on gene expression of the detoxification enzyme family glutathione S-transferases (GSTs) in Arabidopsis thaliana. Treatment of A. thaliana wild-type with AITC resulted in a time- and dose-dependent depletion of cellular GSH. AITC-exposure of mutant lines vtc1 and pad2-1 with elevated and reduced GSH-levels, displayed enhanced and decreased AITC-tolerance, respectively. AITC-exposure also led to increased ROS-levels in the roots and loss of chlorophyll which are symptoms of oxidative stress. Following exposure to AITC, we found that GSH rapidly recovered to the same level as in the control plant, suggesting an effective route for replenishment of GSH or a rapid detoxification of AITC. Transcriptional analysis of genes encoding GSTs showed an upregulation in response to AITC. These findings demonstrate cellular effects by AITC involving a reversible depletion of the GSH-pool, induced oxidative stress, and elevated expression of GST-encoding genes. PMID:25954298

  14. Lactacidosis modulates glutathione metabolism and oxidative glutamate toxicity.

    PubMed

    Lewerenz, Jan; Dargusch, Richard; Maher, Pamela

    2010-04-01

    Lactate and acidosis increase infarct size in humans and in animal models of cerebral ischemia but the mechanisms by which they exert their neurotoxic effects are poorly understood. Oxidative glutamate toxicity is a form of nerve cell death, wherein glutamate inhibits cystine uptake via the cystine/glutamate antiporter system leading to glutathione depletion, accumulation of reactive oxygen species and, ultimately, programmed cell death. Using the hippocampal cell line, HT22, we show that lactate and acidosis exacerbate oxidative glutamate toxicity and further decrease glutathione levels. Acidosis but not lactate inhibits system , whereas both acidosis and lactate inhibit the enzymatic steps of glutathione synthesis downstream of cystine uptake. In contrast, when glutathione synthesis is completely inhibited by cystine-free medium, acidosis partially protects against glutathione depletion and cell death. Both effects of acidosis are also present in primary neuronal and astrocyte cultures. Furthermore, we show that some neuroprotective compounds are much less effective in the presence of lactacidosis. Our findings indicate that lactacidosis modulates glutathione metabolism and neuronal cell death. Furthermore, lactacidosis may interfere with the action of some neuroprotective drugs rendering these less likely to be therapeutically effective in cerebral ischemia. PMID:20132475

  15. Effect of vitamin E on glutathione-dependent enzymes.

    PubMed

    van Haaften, Rachel I M; Haenen, Guido R M M; Evelo, Chris T A; Bast, Aalt

    2003-01-01

    Reactive oxygen species and various electrophiles are involved in the etiology of diseases varying from cancer to cardiovascular and pulmonary disorders. The human body is protected against damaging effects of these compounds by a wide variety of systems. An important line of defense is formed by antioxidants. Vitamin E (consisting of various forms of tocopherols and tocotrienols) is an important fat-soluble, chain-breaking antioxidant. Besides working as an antioxidant, this compound possesses other functions with possible physiological relevance. The glutathione-dependent enzymes form another line of defense. Two important enzymes in this class are the free radical reductase and glutathione S-transferases (GSTs). The GSTs are a family of phase II detoxification enzymes. They can catalyze glutathione conjugation with various electrophiles. In most cases the electrophiles are detoxified by this conjugation, but in some cases the electrophiles are activated. Antioxidants do not act in isolation but form an intricate network. It is, for instance, known that vitamin E, together with glutathione (GSH) and a membrane-bound heat labile GSH-dependent factor, presumably an enzyme, can prevent damaging effects of reactive oxygen species on polyunsaturated fatty acids in biomembranes (lipid peroxidation). This manuscript reviews the interaction between the two defense systems, vitamin E and glutathione-dependent enzymes. On the simplest level, antioxidants such as vitamin E have protective effects on glutathione-dependent enzymes; however, we will see that reality is somewhat more complicated. PMID:12959415

  16. Mucosal Immune Development in Early Life: Setting the Stage.

    PubMed

    Brugman, Sylvia; Perdijk, Olaf; van Neerven, R J Joost; Savelkoul, Huub F J

    2015-08-01

    Our environment poses a constant threat to our health. To survive, all organisms must be able to discriminate between good (food ingredients and microbes that help digest our food) and bad (pathogenic microbes, viruses and toxins). In vertebrates, discrimination between beneficial and harmful antigens mainly occurs at the mucosal surfaces of the respiratory, digestive, urinary and genital tract. Here, an extensive network of cells and organs form the basis of what we have come to know as the mucosal immune system. The mucosal immune system is composed of a single epithelial cell layer protected by a mucus layer. Different immune cells monitor the baso-lateral side of the epithelial cells and dispersed secondary lymphoid organs, such as Peyer's patches and isolated lymphoid follicles are equipped with immune cells able to mount appropriate and specific responses. This review will focus on the current knowledge on host, dietary and bacterial-derived factors that shape the mucosal immune system before and after birth. We will discuss current knowledge on fetal immunity (both responsiveness and lymphoid organ development) as well as the impact of diet and microbial colonization on neonatal immunity and disease susceptibility. Lastly, inflammatory bowel disease will be discussed as an example of how the composition of the microbiota might predispose to disease later in life. A fundamental understanding of the mechanisms involved in mucosal immune development and tolerance will aid nutritional intervention strategies to improve health in neonatal and adult life. PMID:25666708

  17. Awareness assessment in Turkish subpopulation with chronic oral mucosal diseases

    PubMed Central

    Okumus, Ozlem; Kalkan, Sevda; Keser, Gaye; Pekiner, Filiz Namdar

    2015-01-01

    Objectives: The aim of this study was to evaluate the awareness of group Turkish patients with chronic oral mucosal diseases by chronic oral mucosal diseases questionnaires (COMDQ). Materials and Methods: Eighty patients with chronic oral mucosal diseases were participated in the study. A detailed medical history of each patient was taken, and all the COMDQ questions, which were translated from English version, were filled out. The data were analyzed with the IBM Statistical Package for Social Sciences Statistics 22.0. Results: The mean ages of patients were 48.91 13.36 years. Of the total 80 cases of chronic oral mucosal diseases identified 52 (65%) were female and 28 (35%) male. The standardized mean scores for COMDQ were 1.72 1.11 for pain and functional limitation, 1.09 0.94 for medication and treatment, 2.31 1.06 for social and emotional, and 2.27 0.83 for patient support, respectively. Conclusions: The results of this study indicate that the Turkish version of the COMDQ has the profitable psychometric peculiarity and comfortable to patients with chronic oral mucosal diseases in Turkey.

  18. Airway structural cells regulate TLR5-mediated mucosal adjuvant activity.

    PubMed

    Van Maele, L; Fougeron, D; Janot, L; Didierlaurent, A; Cayet, D; Tabareau, J; Rumbo, M; Corvo-Chamaillard, S; Boulenouar, S; Jeffs, S; Vande Walle, L; Lamkanfi, M; Lemoine, Y; Erard, F; Hot, D; Hussell, T; Ryffel, B; Benecke, A G; Sirard, J-C

    2014-05-01

    Antigen-presenting cell (APC) activation is enhanced by vaccine adjuvants. Most vaccines are based on the assumption that adjuvant activity of Toll-like receptor (TLR) agonists depends on direct, functional activation of APCs. Here, we sought to establish whether TLR stimulation in non-hematopoietic cells contributes to flagellin's mucosal adjuvant activity. Nasal administration of flagellin enhanced T-cell-mediated immunity, and systemic and secretory antibody responses to coadministered antigens in a TLR5-dependent manner. Mucosal adjuvant activity was not affected by either abrogation of TLR5 signaling in hematopoietic cells or the presence of flagellin-specific, circulating neutralizing antibodies. We found that flagellin is rapidly degraded in conducting airways, does not translocate into lung parenchyma and stimulates an early immune response, suggesting that TLR5 signaling is regionalized. The flagellin-specific early response of lung was regulated by radioresistant cells expressing TLR5 (particularly the airway epithelial cells). Flagellin stimulated the epithelial production of a small set of mediators that included the chemokine CCL20, which is known to promote APC recruitment in mucosal tissues. Our data suggest that (i) the adjuvant activity of TLR agonists in mucosal vaccination may require TLR stimulation of structural cells and (ii) harnessing the effect of adjuvants on epithelial cells can improve mucosal vaccines. PMID:24064672

  19. Peri-implant mucositis treatments in humans: a systematic review

    PubMed Central

    Zeza, Blerina; Pilloni, Andrea

    2012-01-01

    Summary Aim Peri-implant mucositis affects 39.4–80% of patients restored with dental implants. If left untreated it evolves in peri-implantitis. Thus far no predictable successful treatment has been reported for peri-implantitis, resulting in implant failure. Proper diagnosis and treatment of peri-implant mucositis is of crucial importance. This study aims to provide a comprehensive review of the available data regarding the effectiveness of peri-implant mucositis treatments in humans, parameters used for the diagnosis and treatment effect evaluation. Materials and methods A literature search for RCT and observational studies on peri-implant mucositis treatments in humans was conducted on Pubmed up to January 2012. CONSORT/STROBE and PRISMA checklists guided the evaluation of studies found and the writing of this review, respectively. Results Only 5 studies fulfilled the selection criteria. Few possibly effective treatments were studied. Diagnostic parameters reported were clinical only, while treatment effect evaluation was based on clinical and microbiological changes, except for one study reporting biochemical analysis. An evident heterogeneity characterized the follow-up intervals and methods used for reporting parameters changes. Conclusions Neither of studied treatments gave complete resolution of peri-implant mucositis. Different treatment strategies need to be studied. Authors suggest guidelines for a protocol of parameters used for determining the sample size, diagnosis and treatment effect, as well as follow-up periods, in order to permit evidence and comparison of different treatments effectiveness. PMID:23386927

  20. Physiology and immunology of mucosal barriers in catfish (Ictalurus spp.).

    PubMed

    Peatman, Eric; Lange, Miles; Zhao, Honggang; Beck, Benjamin H

    2015-01-01

    The mucosal barriers of catfish (Ictalurus spp) constitute the first line of defense against pathogen invasion while simultaneously carrying out a diverse array of other critical physiological processes, including nutrient adsorption, osmoregulation, waste excretion, and environmental sensing. Catfish depend more heavily on mucosal barriers than their terrestrial counterparts as they are continuously interacting with the aquatic microbiota. Our understanding of these barriers, while growing, is still limited relative to that of mammalian model systems. Nevertheless, a combination of molecular and cellular studies in catfish over the last few decades, and particularly within the last few years, has helped to elucidate many of the primary actors and pathways critical to their mucosal health. Here we describe aspects of innate and adaptive immune responses in the primary mucosal tissues (skin, gill, and intestine) of catfish, focusing on mucus-driven responses, pathogen recognition, soluble mediators, and immunoglobulin and T-cell derived immunity. Modulation of mucosal barriers will be critical moving forward for crafting better diets, improving vaccine delivery, enhancing water quality, and ensuring sustainable production practices in catfish. PMID:26716071

  1. Induction of apoptosis of lymphocytes in rat mucosal immune system

    PubMed Central

    Chen, Xue-Qing; Zhang, Wan-Dai; Song, Yu-Gang; Zhou, Dian-Yuan

    1998-01-01

    AIM: To undergo apoptosis during negative and positive selection processes in rat mucosal immune system which are implicated in the pathogenesis of various mucosal diseases. METHODS: Female Sprague-Dawley rats were given protein synthesis inhibitor, cycloheximide, intravenously or intraperitoneally, an apoptosis was recognized by morphological hallmark under light and electronmicroscopy, and the expression of proliferating cell nuclear antigen was visualized immunohistochemically. RESULTS: The apoptosis of mucosal lymphocytes in the digestive tract, as well as in trachea, uterus and lacrimal gland was induced by cycloheximide ( > 1.0 mgkg-1 body weight), which were located mainly in lamina propria and germinal centers of lymphoid nodules. At the same time, a portion of crypt epithelial cells of proliferating zone in small and large intestine, and the epithelial cells in genital tract were also found to undergo apoptosis. Immunostainings showed that apoptotic cells expressed proliferating cell nuclear antigen. CONCLUSION: Apoptosis of lymphocytes in mucosal immune system can be induced by cycloheximide. This model will facilitate the understanding of normal mucosal immune system and its role in the pathogenesis of related diseases such as inflammatory bowel diseases. PMID:11819221

  2. Ontogeny of mucosal immunity--environmental and behavioral influences.

    PubMed

    Husband, A J; Gleeson, M

    1996-09-01

    Since mucosal surfaces represent the interface between the host and the environment and are the most common portal of pathogen entry, early development of functional mucosal immune defense is essential for survival. The development of mucosal immune function is profoundly influenced by maternal, environmental, and behavioral factors and although the impact of these is greatest during the prenatal and immediately postnatal periods, their influence extends beyond this period and patterns of development in postnatal life determine many of the immune outcomes in later life. This review will correlate information regarding age-related changes occurring in mucosal-associated lymphoid tissue from a variety of animal models and in humans and will explore how the interactions which exist between the immune and neuroendocrine systems orchestrate these effects. In particular the role of prenatal and postnatal stressors, feeding patterns, nutritional factors, infections, and exposure to allergens and toxins are addressed. A clear understanding of the way in which these factors interact to influence development and control of mucosal immune function will assist in the design of neonatal vaccination and disease management strategies. PMID:8954593

  3. Effect of smoking on folate levels in buccal mucosal cells.

    PubMed

    Piyathilake, C J; Hine, R J; Dasanayake, A P; Richards, E W; Freeberg, L E; Vaughn, W H; Krumdieck, C L

    1992-10-21

    The objective of the study was to document the existence of localized deficiency of folate in a tissue exposed to cigarette smoke, by analysis of oral and circulatory levels of this vitamin in smokers and non-smokers. Buccal mucosal cells and blood samples were collected from 25 smokers and 34 non-smokers. The Health Habits and History Questionnaire was completed by each subject. A 96-well plate L. casei assay, along with preincubation with a folate-free chick pancreas pteroyl-gamma-glutamyl hydrolase, was used to quantitate total buccal mucosal cell folates. The reproducibility (CV 5 to 7%) and recovery (95 to 106%) of the folate assay were satisfactory. Smokers had significantly lower buccal mucosal cell folate levels than did non-smokers. The mean plasma folate level of smokers although within normal limits, was also significantly lower than that of non-smokers. There were no significant differences in mean dietary folate intake or in alcohol consumption between the 2 groups. The strength of the positive association between smoking and plasma and buccal mucosal cell folate deficiency (by any definition) was moderate to strong and statistically significant. Our results indicate that cigarette smoking may result in a localized folate deficiency in buccal mucosal cells, independent of the plasma folate levels. PMID:1399138

  4. EFFECT OF EXOGENOUS GLUTATHIONE, GLUTATHIONE REDUCTASE, CHLORINE DIOXIDE, AND CHLORITE ON OSMOTIC FRAGILITY OF RAT BLOOD IN VITRO

    EPA Science Inventory

    Chlorine dioxide (ClO2), chlorite (ClO2(-1)), and chlorate (ClO3(-1)) in drinking water decreased blood glutathione and RBC osmotic fragility in vivo. The osmotic fragility and glutathione content were also studied in rat blood treated with ClO2, ClO2(-1), ClO3(-1) in vitro. RBC ...

  5. Short-term effect of dietary yeast nucleotide supplementation on small intestinal enzyme activities, bacterial populations and metabolites and ileal nutrient digestibilities in newly weaned pigs.

    PubMed

    Sauer, N; Eklund, M; Roth, S; Rink, F; Jezierny, D; Bauer, E; Mosenthin, R

    2012-08-01

    In previous studies, dietary nucleotides have been shown to improve performance in single-stomached animals by promoting the renewal of small intestine epithelial cells and by influencing the activity and composition of the microbial community in the digestive tract. The present experiment was carried out with 12 barrows weaned at the age of 18 days and fitted with a simple T-cannula at the distal ileum. To determine short-term effects of dietary yeast nucleotides, the piglets received a grain-soybean meal-based basal diet with or without supplementation of 1 g/kg of a dried yeast product containing free nucleotides. Dietary supplementation with yeast did not affect bacterial numbers in the ileum as well as ileal concentrations of individual short-chain fatty acids (SCFA), total SCFA and total lactic acid (p > 0.05). Moreover, there was no effect of supplemental yeast nucleotides on ileal ?-amylase, leucine amino peptidase, maltase and lactase activities (p > 0.05), as well as on ileal dry matter, crude protein and crude fibre digestibilities (p > 0.05). In conclusion, short-term supplementation with dietary yeast nucleotides did not affect microbial metabolite concentrations, bacterial numbers and enzyme activities in the ileal digesta as well as ileal nutrient digestibilities of newly weaned pigs. PMID:21797935

  6. Mucosal vaccination by adenoviruses displaying reovirus sigma 1.

    PubMed

    Weaver, Eric A; Camacho, Zenaido T; Hillestad, Matthew L; Crosby, Catherine M; Turner, Mallory A; Guenzel, Adam J; Fadel, Hind J; Mercier, George T; Barry, Michael A

    2015-08-01

    We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber ?-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. When wereused to immunize mice by the intranasal route, Ad5-R3-sigma produced higher serum and vaginal antibody responses than Ad5. These data suggest optimized Ad-sigma vectors may be useful vectors for mucosal vaccination. PMID:25827529

  7. Oral mucositis induced by anticancer treatments: physiopathology and treatments

    PubMed Central

    Lionel, D'Hondt; Christophe, Lonchay; Marc, Andr; Jean-Luc, Canon

    2006-01-01

    Oral mucositis is a frequent and devastating side effect of anticancer treatments. It impairs the patient's quality of life and also can be life threatening because severe infections and delayed or incomplete anticancer treatments may result. This problem has been largely overlooked and underestimated in the past. However, recently studies have been performed to precisely identify the epidemiology, cost, consequences, physiopathology, and treatments of oral mucositis. Clinical guidelines have recently been published to help the daily management of this frequent complication. In addition, some innovative new drugs, including palifermin, have been developed to prevent and treat this major side effect of cancer treatments. In this paper we summarize the recent developments of oral mucositis management. PMID:18360589

  8. 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

  9. The mucosal immune system: from fundamental concepts to vaccine development.

    PubMed

    McGhee, J R; Mestecky, J; Dertzbaugh, M T; Eldridge, J H; Hirasawa, M; Kiyono, H

    1992-01-01

    Recent studies in experimental animals and humans have shown that the mucosal immune system, which is characterized by secretory IgA (S-IgA) antibodies as the major humoral defence factor, contains specialized lymphoid tissues where antigens are encountered from the environment, are taken up and induce B- and T-cell responses. This event is followed by an exodus of specific lymphocytes, which home to various effector sites such as the lamina propria regions and glands. These responses are regulated by T cells and cytokines and lead to plasma cell differentiation and subsequent production of S-IgA antibodies in external secretions. This knowledge has led to practical approaches for vaccine construction and delivery into mucosal inductive sites in an effort to elicit host protection at mucosal surfaces where the infection actually occurs. PMID:1539467

  10. The mucosal inflammatory response to non-typhoidal Salmonella in the intestine is blunted by IL-10 during concurrent malaria parasite infection

    PubMed Central

    Mooney, Jason P.; Butler, Brian P.; Lokken, Kristen L.; Xavier, Mariana N.; Chau, Jennifer Y.; Schaltenberg, Nicola; Dandekar, Satya; George, Michael D.; Santos, Renato L.; Luckhart, Shirley; Tsolis, Renée M.

    2014-01-01

    SUMMARY Co-infection can markedly alter the response to a pathogen, thereby changing its clinical presentation. For example, non-typhoidal Salmonella (NTS) serotypes are associated with gastroenteritis in immunocompetent individuals. In contrast, individuals with severe pediatric malaria can develop bacteremic infections with NTS, during which symptoms of gastroenteritis are commonly absent. Here, we report that in both a ligated ileal loop model and a mouse colitis model, malaria parasites caused a global suppression of gut inflammatory responses and blunted the neutrophil influx that is characteristic of NTS infection. Further, malaria parasite infection led to increased recovery of S. Typhimurium from the draining mesenteric lymph node of mice. In the mouse colitis model, blunted intestinal inflammation during NTS infection was independent of anemia, but instead required parasite-induced synthesis of IL-10. Blocking of IL-10 in co-infected mice reduced dissemination of S. Typhimurium to the mesenteric lymph node, suggesting that induction of IL-10 contributes to development of disseminated infection. Thus, IL-10 produced during the immune response to malaria in this model contributes to suppression of mucosal inflammatory responses to invasive NTS, which may contribute to differences in the clinical presentation of NTS infection in the setting of malaria. PMID:24670425

  11. The mucosal inflammatory response to non-typhoidal Salmonella in the intestine is blunted by IL-10 during concurrent malaria parasite infection.

    PubMed

    Mooney, J P; Butler, B P; Lokken, K L; Xavier, M N; Chau, J Y; Schaltenberg, N; Dandekar, S; George, M D; Santos, R L; Luckhart, S; Tsolis, R M

    2014-11-01

    Coinfection can markedly alter the response to a pathogen, thereby changing its clinical presentation. For example, non-typhoidal Salmonella (NTS) serotypes are associated with gastroenteritis in immunocompetent individuals. In contrast, individuals with severe pediatric malaria can develop bacteremic infections with NTS, during which symptoms of gastroenteritis are commonly absent. Here we report that, in both a ligated ileal loop model and a mouse colitis model, malaria parasites caused a global suppression of gut inflammatory responses and blunted the neutrophil influx that is characteristic of NTS infection. Further, malaria parasite infection led to increased recovery of Salmonella enterica serotype Typhimurium from the draining mesenteric lymph node (MLN) of mice. In the mouse colitis model, blunted intestinal inflammation during NTS infection was independent of anemia but instead required parasite-induced synthesis of interleukin (IL)-10. Blocking of IL-10 in coinfected mice reduced dissemination of S. Typhimurium to the MLN, suggesting that induction of IL-10 contributes to development of disseminated infection. Thus IL-10 produced during the immune response to malaria in this model contributes to suppression of mucosal inflammatory responses to invasive NTS, which may contribute to differences in the clinical presentation of NTS infection in the setting of malaria. PMID:24670425

  12. Long-Term Followup of Patients with Active J-Reservoirs after Restorative Proctocolectomy for Ulcerative Colitis with regard to Reservoir Function, Mucosal Changes, and Quality of Life

    PubMed Central

    Rkke, Ola; Iversen, Knut; Olsen, Torill; Ristesund, Slvi-May; Eide, Geir Egil; Turowski, Gitta Erika

    2011-01-01

    Objective. Study the functional results and mucosal changes in the ileal pouch after restorative proctocolectomy with J-reservoir for ulcerative colitis. Material and Methods. Followup study of 125 patients with J-reservoir with one disease-specific- and one general (SF-36) quality of life-questionnaire, rectoscopy with biopsies, and stool samples to evaluate inflammation, dysplasia, presence of Helicobacter pylori and calprotectin level. Results. Fourteen J-reservoirs were removed or deactivated, leaving 111 patients for followup. The followup time was 6.8 (115) years. 87.4% of the patients were satisfied. 93.1% had some kind of functional restriction: food- (75.5%), social- (28.9%), physical- (37%) or sexual restriction (15.3%). 18.6% had often or sometimes faecal incontinence. Low daytime faecal frequency was associated with good quality of life. 13 patients (12.6%) had a less favourable result. There was no pouch-dysplasia. Calprotectin levels were increased in patients with visible pouch inflammation or history of pouchitis. HP was diagnosed by RUT in 42.3%, but was not associated with inflammation or pouchitis. Conclusions. Most patients were satisfied with the J-reservoir in spite of a high frequency of various restrictions. 12.6% (13 patients) had a less favourable functional result, partly due to a high frequency of defecations, pain, pouchitis and inflammation. PMID:21991508

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

    PubMed

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

    2015-12-01

    Delivering vaccine antigens to mucosal surfaces is potentially very attractive, especially as protection from mucosal infections may be mediated by local immune responses. However, to date mucosal immunization has had limited successes, with issues of both safety and poor immunogenicity. One approach to improve immunogenicity is to develop adjuvants that are effective and safe at mucosal surfaces. Differences in immune responses between mice and men have overstated the value of some experimental adjuvants which have subsequently performed poorly in the clinic. Due to their closer similarity, non-human primates can provide a more accurate picture of adjuvant performance. In this study we immunised rhesus macaques (Macaca mulatta) using a unique matrix experimental design that maximised the number of adjuvants screened while reducing the animal usage. Macaques were immunised by the intranasal, sublingual and intrarectal routes with the model protein antigens keyhole limpet haemocyanin (KLH), ?-galactosidase (?-Gal) and ovalbumin (OVA) in combination with the experimental adjuvants Poly(I:C), Pam3CSK4, chitosan, Thymic Stromal Lymphopoietin (TSLP), MPLA and R848 (Resiquimod). Of the routes used, only intranasal immunization with KLH and R848 induced a detectable antibody response. When compared to intramuscular immunization, intranasal administration gave slightly lower levels of antigen specific antibody in the plasma, but enhanced local responses. Following intranasal delivery of R848, we observed a mildly inflammatory response, but no difference to the control. From this we conclude that R848 is able to boost antibody responses to mucosally delivered antigen, without causing excess local inflammation. PMID:26697975

  14. Do glutathione levels decline in aging human brain?

    PubMed

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

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. PMID:26845616

  15. Altered glutathione homeostasis in animals prenatally exposed to lipopolysaccharide

    PubMed Central

    Zhu, Yuangui; Carvey, Paul M.; Ling, Zaodung

    2007-01-01

    We previously reported that injection of bacterial lipopolysaccharide (LPS) into gravid female rats at embryonic day 10.5 resulted in a birth of offspring with fewer than normal dopamine (DA) neurons along with innate immunity dysfunction and many characteristics seen in Parkinsons disease (PD) patients. The LPS-exposed animals were also more susceptible to secondary toxin exposure as indicated by an accelerated DA neuron loss. Glutathione (GSH) is an important antioxidant in the brain. A disturbance in glutathione homeostasis has been proposed for the pathogenesis of PD. In this study, animals prenatally exposed to LPS were studied along with an acute intranigral LPS injection model for the status of glutathione homeostasis, lipid peroxidation, and related enzyme activities. Both prenatal LPS exposure and acute LPS injection produced a significant GSH reduction and increase in oxidized GSH (GSSG) and lipid peroxide (LPO) production. Activity of ?-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in de novo GSH synthesis, was up-regulated in acute supranigral LPS model but was reduced in the prenatal LPS model. The GCS light subunit protein expression was also down-regulated in prenatal LPS model. GSH redox recycling enzyme activities (glutathione peroxidase, GPx and glutathione reducdase, GR) and glutathione S-transferase (GST), ?-glutamyl transpeptidase (?-GT) activities were all increased in prenatal LPS model. Prenatal LPS exposure and aging synergized in GSH level and GSH related enzyme activities except for those (GR, GST, and ?-GT) with significant regional variations. Additionally, prenatal LPS exposure produced a reduction of DA neuron count in the substantia nigra (SN). These results suggest that prenatal LPS exposure may cause glutathione homeostasis disturbance in offspring brain and render DA neurons susceptible to the secondary neurotoxin insult. PMID:17291629

  16. Mucosal versus muscle pain sensitivity in provoked vestibulodynia

    PubMed Central

    Witzeman, Kathryn; Nguyen, Ruby HN; Eanes, Alisa; As-Sanie, Sawsan; Zolnoun, Denniz

    2015-01-01

    Background An estimated 8.3%16% of women experience vulvovaginal discomfort during their lifetime. Frequently these patients report provoked pain on contact or with attempted intercourse, commonly referred to as provoked vestibulodynia (PVD). Despite the burden of this condition, little is known about its potential etiologies including pelvic floor muscular dysfunction and mucosal components. This knowledge would be beneficial in developing targeted therapies including physical therapy. Objective To explore the relative contribution of mucosal versus muscle pain sensitivity on pain report from intercourse among women with PVD. Design In this proof of concept study, 54 women with PVD underwent a structured examination assessing mucosal and pelvic muscle sensitivity. Methods We examined three mucosal sites in the upper and lower vestibule. Patients were asked to rate their pain on cotton swab palpation of the mucosa using a 10-point visual analog scale. Muscle pain was assessed using transvaginal application of pressure on right and left puborectalis, and the perineal muscle complex. The Gracely pain scale (0100) was used to assess the severity of pain with intercourse, with women rating the lowest, average, and highest pain levels; a 100 rating the highest level of pain. Results The lower vestibules mucosa 5.81 (standard deviation =2.83) was significantly more sensitive than the upper vestibule 2.52 (standard deviation =2.6) (P<0.01) on exam. However, mucosal sensitivity was not associated with intercourse pain, while muscle sensitivity was moderately associated with both average and highest intensity of intercourse pain (r=?0.46, P=0.01 and r=?0.42, P=0.02), respectively. Conclusion This preliminary study suggests that mucosal measures alone may not sufficiently capture the spectrum of clinical pain report in women with PVD, which is consistent with the empirical success of physical therapy in this population. PMID:26316805

  17. 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.

  18. 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, 731743. PMID:25387359

  19. 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.

  20. Live bacterial delivery systems for development of mucosal vaccines.

    PubMed

    Thole, J E; van Dalen, P J; Havenith, C E; Pouwels, P H; Seegers, J F; Tielen, F D; van der Zee, M D; Zegers, N D; Shaw, M

    2000-02-01

    By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed rational development of new and improved bacterial carriers and more effective gene expression systems. These advances have improved the performance and versatility of these delivery systems to induce mucosal immunity to recombinant antigens in animal models. Application of these (improved) technologies for development of human vaccines is still limited and awaits further exploration. PMID:11249657

  1. Oral mucosal manifestations in some genodermatoses: correlation with cutaneous lesions.

    PubMed

    Nico, Marcello Menta Simonsen; Hammerschmidt, Mariana; Lourenço, Silvia Vanessa

    2013-01-01

    The clinical picture of several genetic skin diseases may include the presence of oral mucosal lesions. These manifestations, however, have not been granted much attention in most dermatological publications. In this article, we fully review the oral mucosal lesions of tuberous sclerosis, dyskeratosis congenita, lipoidoproteinosis, Cowden disease, Darier's disease and pachyonychya congenita and compare these with their respective cutaneous lesions. Some dental aspects are discussed as well. This unifying approach may allow a better understanding of these oral lesions, avoiding obscure nomenclature and classification. PMID:24001555

  2. Improved Techniques for Endoscopic Mucosal Resection (EMR) in Colorectal Adenoma

    PubMed Central

    Sold, Moritz; Khler, Georg

    2014-01-01

    Summary Background Endoscopic therapy of colorectal adenomas and early cancers is a standard method. Besides oncological criteria, the method is limited by polyp location, size, and texture. Method Based on the current literature, technical modifications and developments in endoscopic mucosal resection are described. Results Numerous approaches exist to improve the conditions of resection, including optimisation of mucosal elevation and modification of techniques, tools, and devices. Conclusion Endoscopic therapy of sessile and flat colorectal polyps remains a challenge. Some of the presented modifications can help to address this challenge. PMID:26286120

  3. Mucosal genetic immunization through microspherebased oral carriers

    PubMed Central

    Rosli, Rozita; Nograles, Nadine; Hanafi, Aimi; Nor Shamsudin, Mariana; Abdullah, Syahril

    2013-01-01

    Polymeric carriers in the form of cellulose acetate phthalate (CAP) and alginate (ALG) microspheres were used for encapsulation of plasmid DNA for oral mucosal immunization. Access into the intestinal mucosa by pVAX1 eukaryotic expression plasmid vectors carrying gene-coding sequences, either for the cholera enterotoxin B subunit (ctxB) immunostimulatory antigen or the green fluorescent protein (GFP), delivered from both types of microsphere carriers were examined in orally immunized BALB/c mice. Demonstration of transgene protein expression and IgA antibody responses at local mucosal sites suggest immunological response to a potential oral DNA vaccine formulated within the microsphere carriers. PMID:24051430

  4. Gastric mucosal morphology and faecal blood loss during ethanol ingestion

    PubMed Central

    Dinoso, V. P.; Meshkinpour, H.; Lorber, S. H.

    1973-01-01

    The faecal blood loss of six alcoholic subjects with normal gastric mucosa, six with superficial gastritis, and six with atrophic gastritis was studied before and during ingestion of 40% v/v ethanol using 51Cr-tagged red blood cells. No significant change in faecal blood loss was observed in the normal mucosa and superficial gastritis groups but all subjects with atrophic gastritis had significant increases of faecal blood loss during ethanol ingestion. These observations suggest that gastric mucosal morphology may be an important determinant of gastric mucosal bleeding during the ingestion of alcohol. PMID:4706910

  5. Korean ginseng modulates the ileal microbiota and mucin gene expression in the growing rat.

    PubMed

    Han, Kyoung-Sik; Balan, Prabhu; Hong, Hee-Do; Choi, Won-Il; Cho, Chang-Won; Lee, Young-Chul; Moughan, Paul J; Singh, Harjinder

    2014-07-25

    The study was conducted to investigate whether oral administration of Korean ginseng powders can modulate gut microbiota as well as intestinal mucin production at the translational and transcriptional levels in the ileum of the growing rat. Thirty individually caged Sprague-Dawley male rats were allocated to three groups (n = 10) and fed for 21 days either a basal control diet or one of the two treatment diets each containing white or red Korean ginseng (WG or RG) powder. Bacterial DNA was extracted from ileal digesta and subjected to quantitative real-time PCR (qPCR) using primers for total bacteria, Lactobacillus, Bifidobacteria, Escherichia coli, Bacteroides, and Clostridium strains. The qPCR results showed that consumption of WG or RG powder significantly increased the number of total bacteria and Lactobacillus strains compared to the control group. Consumption of WG powder increased mRNA expression of the Muc2 gene in the small intestine compared to the control group. There was no effect of WG or RG on the small intestinal digesta mucin content. Correlation analysis showed that expression of the Muc2 gene was significantly associated with the number of total bacteria (r = 0.52, P < 0.05) and Lactobacillus strains (r = 0.53, P < 0.05), respectively. Furthermore, the number of Lactobacillus strains was significantly correlated with the number of total bacteria (r = 0.87, P < 0.05). Consumption of the WG powder modulated the intestinal ecosystem of the growing rat and intestinal mucin gene expression. PMID:24832824

  6. Ileal mucosa-associated lymphoid tissue lymphoma presenting with small bowel obstruction: a case report.

    PubMed

    Kinkade, Zoe; Esan, Olukemi A; Rosado, Flavia G; Craig, Michael; Vos, Jeffrey A

    2015-01-01

    Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT Lymphoma) of the gastrointestinal tract commonly involves the stomach in the setting of concurrent Helicobacter pylori (H. pylori) infection. Primary ileal MALT lymphoma is rare, and has not been associated with a specific infectious disease. We report a case of a 58-year-old man who presented to the emergency department with constipation and abdominal distension, and signs of an obstructing mass on computed tomography scan. A small bowel resection was performed which revealed an 8cm saccular dilatation with thickened bowel wall and subjacent thickened tan-yellow tissue extending into the mesentery. Histologically, there was a diffuse lymphoid infiltrate consisting of small atypical cells with monocytoid features. These cells were CD20-positive B-lymphocytes that co-expressed BCL-2 and were negative for CD5, CD10, CD43, and cyclin D1 on immunohistochemical studies. Kappa-restricted plasma cells were also identified by in situ hybridization. The overall proliferation index was low with Ki-67 immunoreactivity in approximately 10% of cells. No areas suspicious for large cell or high grade transformation were identified. The pathologic findings were diagnostic of an extranodal marginal zone lymphoma involving the ileum, with early involvement of mesenteric lymph nodes. Small hypermetabolic right mesenteric and bilateral hilar lymph nodes were identified by imaging. The bone marrow biopsy showed no evidence of involvement by lymphoma. The patient was clinically considered advanced stage and opted for therapy with rituximab infusions. After six months of therapy, follow-up radiologic studies demonstrated significant decrease in size of the mesenteric lymph nodes. PMID:26178711

  7. Bovine ileal intraepithelial lymphocytes represent target cells for Shiga toxin 1 from Escherichia coli.

    PubMed

    Menge, Christian; Blessenohl, Maike; Eisenberg, Tobias; Stamm, Ivonne; Baljer, Georg

    2004-04-01

    The discovery that bovine peripheral lymphocytes are sensitive to Stx1 identified a possible mechanism for the persistence of infections with Shiga toxin (Stx)-producing Escherichia coli (STEC) in the bovine reservoir host. If intraepithelial lymphocytes (IEL) are also sensitive to Stx1, the idea that Stx1 affects inflammation in the bovine intestine is highly attractive. To prove this hypothesis, ileal IEL (iIEL) were prepared from adult cattle, characterized by flow cytometry, and subjected to functional assays in the presence and absence of purified Stx1. We found that 14.9% of all iIEL expressed Gb(3)/CD77, the Stx1 receptor on bovine lymphocytes, and 7.9% were able to bind the recombinant B subunit of Stx1. The majority of Gb(3)/CD77(+) cells were activated CD3(+) CD6(+) CD8 alpha(+) T cells, whereas only some CD4(+) T cells and B cells expressed Gb(3)/CD77. However, Stx1 blocked the mitogen-induced transformation to enlarged blast cells within all subpopulations to a similar extent and significantly reduced the percentage of Gb(3)/CD77(+) cells. Although Stx1 did not affect the natural killer cell activity of iIEL, the toxin accelerated the synthesis of interleukin-4 (IL-4) mRNA and reduced the amount of IL-8 mRNA in bovine iIEL cultures. Because the intestinal system comprises a rich network of interactions between different types of cells and any dysfunction may influence the course of intestinal infections, this demonstration that Stx1 can target bovine IEL may be highly relevant for our understanding of the interplay between STEC and its reservoir host. PMID:15039308

  8. Behavioural profile and human adaptation of survivors after radical cystectomy and ileal conduit

    PubMed Central

    2014-01-01

    Background There is a lack of good data in the literature evaluating the Health-Related Quality of Life (HR- QoL) in patients with urinary diversions. The aim of this study was to examine the changes in expectation and needs in terms of human adaptation and behavioural profiles in patients with ileal conduit (IC) after radical cystectomy (RC) for bladder cancer (BC). Materials and methods A qualitative, multicenter cross-sectional study using a “narrative based” approach was planned. We proceed with a sampling reasoned choice (purposive), selecting groups of patients with follow-up from one up to more than 7 years after surgery. Data were collected through individual interviews. Results Thirty patients participated in the study. The processing of the interviews allowed us to identify 2 major profiles: positive and negative. Patients with a positive profile resumed normal daily activities with no or limited restrictions both on the personal and the social level. This profile reflects a good HR-QoL. The negative profile reflects the patients for whom the ostomy has meant a worsening of HR-QoL. A positive profile was statistically more frequent in older patients (p = 0.023), with a longer follow-up (p = 0.042) and less complications rates (p = 0.0002). According to the length of follow-up and the occurrence of complitations, we identified further 5 intermediate profiles. Conclusions Patients’ satisfaction is related to the degree of adaptation to their new life with an urinary stoma and its correct management. Live “with urinary diversion” represents a new phase of life and not a deterioration. PMID:24708662

  9. Metabolizable energy, nitrogen balance, and ileal digestibility of amino acids in quality protein maize for pigs

    PubMed Central

    2014-01-01

    Background To compare the nutritional value and digestibility of five quality protein maize (QPM) hybrids to that of white and yellow maize, two experiments were carried out in growing pigs. In experiment 1, the energy metabolizability and the nitrogen balance of growing pigs fed one of five QPM hybrid diets were compared against those of pigs fed white or yellow maize. In experiment 2, the apparent and standardized ileal digestibility (AID and SID, respectively) of proteins and amino acids from the five QPM hybrids were compared against those obtained from pigs fed white and yellow maize. In both experiments, the comparisons were conducted using contrasts. Results The dry matter and nitrogen intakes were higher in the pigs fed the QPM hybrids (P?

  10. Digestibility of fibre sources and molecular weight distribution of fibre fractions in ileal digesta of growing pigs.

    PubMed

    Ivarsson, Emma; Andersson, Roger; Lindberg, Jan Erik

    2012-12-01

    Seven post-valve T-caecum cannulated growing pigs were used in a change-over experiment with four diets and four 14-day periods to evaluate the total tract apparent digestibility (TTAD) and the ileal apparent digestibility (IAD) of diets with inclusion of chicory forage (CFO), sugar beet pulp (SBP), wheat bran (WB) and grass meal (GM), as well as the TTAD of the mentioned fibre sources. Moreover, this experiment evaluated the molecular weight distribution of soluble non-starch polysaccharide (NSP) fractions in diet and ileal digesta from pigs fed the CFO and SBP diets. The experimental diets were balanced to have similar NSP content and compromised of one part of the basal diet and one part of the four fibre sources (CFO, SBP, WB and GM). In addition, all pigs were fed the basal diet during a 14-day period before and after the experimental periods. Diet affected the TTAD of all dietary components except glucose. The TTAD of organic matter (OM) was higher for Diet SBP than for Diets WB and CFO, showing both were higher than Diet GM. The TTAD of NSP was higher for Diet SBP than Diets WB and GM. The IAD of OM was higher in Diet SBP than in the other diets. The IAD of NSP was lower in Diet WB than in the other diets. The TTAD of OM and energy of CFO was 0.430.04 (standard error), which is similar to that reported for commonly used forage crops. The molecular weight distribution in ileal digesta showed different distributions between Diets CFO and SBP as well as between digesta from pigs fed these diets. PMID:23130965

  11. Electrophysiological and Mechanical Characteristics in Human Ileal Motility: Recordings of Slow Waves Conductions and Contractions, In vitro

    PubMed Central

    Ryoo, Seung-Bum; Oh, Heung-Kwon; Moon, Sang Hui; Choe, Eun Kyung; Yu, Sung A; Park, Sung-Hye

    2015-01-01

    Little human tissue data are available for slow waves and migrating motor complexes, which are the main components of small bowel motility. We investigated the electrophysiological and mechanical characteristics of human ileal motility, in vitro. Ileum was obtained from patients undergoing bowel resection. Electrophysiological microelectrode recordings for membrane potential changes and mechanical tension recordings for contraction from smooth muscle strips and ileal segments were performed. Drugs affecting the enteric nervous system were applied to measure the changes in activity. Slow waves were detected with a frequency of 9~10/min. There were no cross-sectional differences in resting membrane potential (RMP), amplitude or frequency between outer and inner circular muscle (CM), suggesting that electrical activities could be effectively transmitted from outer to inner CM. The presence of the interstitial cell of Cajal (ICC) at the linia septa was verified by immunohistochemistry. Contractions of strips and segments occurred at a frequency of 3~4/min and 1~2/min, respectively. The frequency, amplitude and area under the curve were similar between CM and LM. In segments, contractions of CM were associated with LM, but propagation varied with antegrade and retrograde directions. Atropine, NW-oxide-L-arginine, and sodium nitroprusside exhibited different effects on RMP and contractions. There were no cross-sectional differences with regard to the characteristics of slow waves in CM. The frequency of contractions in smooth muscle strips and ileal segments was lower than slow waves. The directions of propagation were diverse, indicating both mixing and transport functions of the ileum. PMID:26557020

  12. Electrophysiological and Mechanical Characteristics in Human Ileal Motility: Recordings of Slow Waves Conductions and Contractions, In vitro.

    PubMed

    Ryoo, Seung-Bum; Oh, Heung-Kwon; Moon, Sang Hui; Choe, Eun Kyung; Yu, Sung A; Park, Sung-Hye; Park, Kyu Joo

    2015-11-01

    Little human tissue data are available for slow waves and migrating motor complexes, which are the main components of small bowel motility. We investigated the electrophysiological and mechanical characteristics of human ileal motility, in vitro. Ileum was obtained from patients undergoing bowel resection. Electrophysiological microelectrode recordings for membrane potential changes and mechanical tension recordings for contraction from smooth muscle strips and ileal segments were performed. Drugs affecting the enteric nervous system were applied to measure the changes in activity. Slow waves were detected with a frequency of 9~10/min. There were no cross-sectional differences in resting membrane potential (RMP), amplitude or frequency between outer and inner circular muscle (CM), suggesting that electrical activities could be effectively transmitted from outer to inner CM. The presence of the interstitial cell of Cajal (ICC) at the linia septa was verified by immunohistochemistry. Contractions of strips and segments occurred at a frequency of 3~4/min and 1~2/min, respectively. The frequency, amplitude and area under the curve were similar between CM and LM. In segments, contractions of CM were associated with LM, but propagation varied with antegrade and retrograde directions. Atropine, N(W)-oxide-L-arginine, and sodium nitroprusside exhibited different effects on RMP and contractions. There were no cross-sectional differences with regard to the characteristics of slow waves in CM. The frequency of contractions in smooth muscle strips and ileal segments was lower than slow waves. The directions of propagation were diverse, indicating both mixing and transport functions of the ileum. PMID:26557020

  13. Class pi glutathione S-transferase: Meisenheimer complex formation.

    PubMed

    Bico, P; Chen, C Y; Jones, M; Erhardt, J; Dirr, H

    1994-08-01

    The enzyme-catalysed formation of the dead-end Meisenheimer complex, 1-(S-glutathionyl)-2,4,6-trinitrocyclohexadienate, between glutathione and 1,3,5-trinitrobenzene by two class pi glutathione S-transferases was studied under equilibrium conditions. The apparent formation constant of the complex at pH6.5, is 1.21 x 10(3) M-1 and 1.47 x 10(3) M-1 for isoenzyme pGSTP1-1 from porcine lung and hGSTP1-1 the human recombinant orthologue, respectively. These values are about 40- to 50-times larger than that determined for the nonenzymatic reaction in solution. Competitive inhibitors in the form of glutathione analogues that bind the G-site (glutathione sulphonate) or both the G-site and the H-site (S-hexylglutathione) regions of the active site markedly diminish complex formation. Comparison of kinetic data for glutathione S-transferase isoenzymes from the pi and mu gene classes suggests that the catalytic efficiencies for nucleophilic aromatic substitution reactions correspond with the ability of the enzyme's active site to stabilise the Meisenheimer complex. Formation of the red-coloured complex in orthorhombic crystals of pGSTP1-1 demonstrated that the crystallized protein retains its catalytically functional conformation in the crystal lattice. PMID:7987257

  14. 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.

  15. Genetic Analysis of Tissue Glutathione Concentrations and Redox Balance

    PubMed Central

    Zhou, Yang; Harrison, David E.; Love-Myers, Kimberly; Chen, Yi; Grider, Arthur; Wickwire, Kathie; Burgess, John R.; Stochelski, Mateusz A.; Pazdro, Robert

    2014-01-01

    Glutathione redox balance ― defined as the ratio GSH/GSSG ― is a critical regulator of cellular redox state, and declines in this ratio are closely associated with oxidative stress and disease. However, little is known about the impact of genetic variation on this trait. Previous mouse studies suggest that tissue GSH/GSSG is regulated by genetic background and is therefore heritable. In this study, we measured glutathione concentrations and GSH/GSSG in liver and kidney of 30 genetically-diverse inbred mouse strains. Genetic background caused an approximately three-fold difference in hepatic and renal GSH/GSSG between the most disparate strains. Haplotype association mapping determined the loci associated with hepatic and renal glutathione phenotypes. We narrowed the number of significant loci by focusing on those located within protein-coding genes, which we now consider to be candidate genes for glutathione homeostasis. No candidate genes were associated with both hepatic and renal GSH/GSSG, suggesting that genetic regulation of GSH/GSSG occurs predominantly in a tissue-specific manner. This is the first quantitative trait loci study to examine the genetic regulation of glutathione concentrations and redox balance in mammals. We identified novel candidate genes that have the potential to redefine our knowledge of redox biochemistry, its regulation, and inform future therapeutic applications. PMID:24613380

  16. Glutathione is required for efficient production of infectious picornavirus virions

    SciTech Connect

    Smith, Allen D. . E-mail: smitha@ba.ars.usda.gov; Dawson, Harry . 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.

  17. Polymer nanomicelles for efficient mucus delivery and antigen-specific high mucosal immunity.

    PubMed

    Noh, Young-Woock; Hong, Ji Hyun; Shim, Sang-Mu; Park, Hye Sun; Bae, Hee Ho; Ryu, Eun Kyoung; Hwang, Jung Hwan; Lee, Chul-Ho; Cho, Seong Hun; Sung, Moon-Hee; Poo, Haryoung; Lim, Yong Taik

    2013-07-22

    Micelles for mucosal immunity: A mucosal vaccine system based on ?-PGA nanomicelles and viral antigens was synthesized. The intranasal administration of the vaccine system induces a high immune response both in the humoral and cellular immunity (see picture). PMID:23765547

  18. A Case of In-Bore Transperineal MRI-Guided Prostate Biopsy of a Patient with Ileal Pouch-Anal Anastomosis

    PubMed Central

    Kongnyuy, Michael; Frye, Thomas; George, Arvin K.; Kilchevsky, Amichai; Iyer, Amogh; Kadakia, Meet; Muthigi, Akhil; Turkbey, Baris; Wood, Brad J.; Pinto, Peter A.

    2015-01-01

    Ulcerative colitis (UC) is an inflammatory disease that specifically affects the colon. Ulcerative colitis is primarily treated medically and refractory disease is treated with proctocolectomy and ileal pouch-anal anastomosis (IPAA). Gastroenterologists advise against digital rectal exams, pelvic radiation therapy, and transrectal ultrasound (TRUS) biopsies of the prostates of ileal pouch-anal anastomosis patients. Any form of pouch manipulation can lead to severe bleeding, inflammation, and pain. Urologists are therefore faced with the challenge of doing a prostate biopsy without a transrectal ultrasound. We report the rare case of a patient with an ileal pouch-anal anastomosis who underwent in-bore transperineal MRI-guided biopsy of the prostate. PMID:26844005

  19. The pleiotropic role of vitamin A in regulating mucosal immunity.

    PubMed

    Sirisinha, Stitaya

    2015-06-01

    The effect of vitamin A on mucosal immunity has never been subjected to extensive studies until recently. We started to work in this area in the early 1970s when we observed that children with protein-calorie malnutrition (PCM) often had defective mucosal immunity, judging from the incidence of respiratory tract infections and diarrhea. We reported that these children had depressed secretory IgA (sIgA) levels in their nasal wash fluids. The IgA level in specimens collected from those superimposed with some degrees of vitamin A deficiency state appeared to be more severely affected. In order to better understand the underlying mechanism associated with this condition, we started to study more detail the deficiency state using experimental vitamin A-deficient rats. From a series of experiments using this animal model, we proposed that vitamin A was needed for transport and/or secretion of sIgA across the mucosa. This conclusion was based on the observation that the secretory component of sIgA synthesized by the epithelial cells of these vitamin A deficient animals was adversely affected as compared to the control animals. From that time onward, much progress has been made by several other groups showing that other mechanisms could also influence the integrity and immune function of the mucosa. For instance, recent studies demonstrated that retinoic acid which is a biologically active form of vitamin A has an essential role in mucosal homeostasis, controlling tolerance and immunity in these non-lymphoid tissues. Such a conclusion was made possible by the availability of sophisticated new molecular biology and genetic engineering techniques together with advances in the field of immunoregulation, e.g., the discovery of dendritic cells (DCs) and T helper cell subsets in 1980s, and the role of Toll-like receptors (TLRs) together with other innate immune regulators in controlling adaptive immune response in the early 1990s. These advances provided considerable new insights into the pleiotropic roles of vitamin A including educating mucosal DCs, differentiation of lymphocyte lineages and imprinting them with mucosal-homing properties as well as in regulating tolerance and immunity. The identification of a novel lymphocyte subpopulation, innate lymphoid cells (ILCs), at the beginning of this century has provided us with an additional insight into a new role of vitamin A in regulating homeostasis at the mucosal surface through influencing ILCs. Another new player that regulates intestinal homeostasis and mucosal immune response is microbiota whose composition is known to vary with vitamin A status. So it appears now that the role of vitamin A on mucosal immunity is far beyond regulating the adaptive Th1-Th2 cell response, but is highly pleiotropic and more complicating, e.g., polarizing the phenotype of mucosal DCs and macrophages, directing gut-homing migration of T and B cells, inducing differentiation of effector T cells and Treg subpopulation, balancing mucosal ILCs subpopulation and influencing the composition of microbiota. In this review, I will attempt to bring together these important advances to provide a comprehensive and contemporary perspective on the role of vitamin A in regulating mucosal immunity. PMID:26141028

  20. Fecal bile acid excretion and messenger RNA expression levels of ileal transporters in high risk gallstone patients

    PubMed Central

    2009-01-01

    Background Cholesterol gallstone disease (GS) is highly prevalent among Hispanics and American Indians. In GS, the pool of bile acids (BA) is decreased, suggesting that BA absorption is impaired. In Caucasian GS patients, mRNA levels for ileal BA transporters are decreased. We aimed to determine fecal BA excretion rates, mRNA levels for ileal BA transporter genes and of regulatory genes of BA synthesis in Hispanic GS patients. Results Excretion of fecal BA was measured in seven GS females and in ten GS-free individuals, all with a body mass index < 29. Participants ingested the stool marker Cr2O3 (300 mg/day) for 10 days, and fecal specimens were collected on the last 3 days. Chromium was measured by a colorimetric method, and BA was quantitated by gas chromatography/mass spectroscopy. Intake of calories, nutrients, fiber and cholesterol were similar in the GS and GS-free subjects. Mean BA excretion levels were 520 80 mg/day for the GS-free group, and 461 105 mg/day for the GS group. Messenger RNA expression levels were determined by RT-PCR on biopsy samples obtained from ileum during diagnostic colonoscopy (14 GS-free controls and 16 GS patients) and from liver during surgery performed at 8 and 10 AM (12 GS and 10 GS-free patients operated on for gastrointestinal malignancies), all with a body mass index < 29. Messenger RNA level of the BA transporter genes for ileal lipid binding protein, multidrug resistance-associated protein 3, organic solute transporter alpha, and organic solute transporter beta were similar in GS and GS-free subjects. Messenger RNA level of Cyp27A1, encoding the enzyme 27?-hydroxylase, the short heterodimer partner and farnesoid X receptor remained unchanged, whereas the mRNA level of Cyp7A1, the rate limiting step of BA synthesis, was increased more than 400% (p < 0.01) in the liver of GS compared to GS-free subjects. Conclusion Hispanics with GS have fecal BA excretion rates and mRNA levels of genes for ileal BA transporters that are similar to GS-free subjects. However, mRNA expression levels of Cyp7A1 are increased in GS, indicating that regulation of BA synthesis is abnormal in Hispanics with GS. PMID:19995447

  1. Renal Transplantation in the Setting of Prior Urinary Diversion: A Case of Poorly Differentiated Adenocarcinoma in an Ileal Conduit

    PubMed Central

    Matulewicz, R.S.; Fryer, J.P.; Yang, X.J.; Goyal, R.; Hairston, J.C.

    2015-01-01

    Though rare, renal transplantation into a bowel containing urinary diversion is necessary in select clinical situations. Compared to renal transplant patients with functional native bladders, patients with urinary diversion have comparable long-term graft and patient survival rates. However, compounding the increased risk of malignancy in those on chronic immunosuppression are the inherent risks of urinary diversion. We present a case report of a high grade adenocarcinoma with neuroendocrine differentiation arising in an ileal conduit and discussion on the pathophysiology, management, and screening of this highly select population.

  2. 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

  3. Human glutathione peroxidase activity in cases of high selenium exposures

    SciTech Connect

    Valentine, J.L.; Faraji, B.; Kang, H.K.

    1988-02-01

    Four communities with water supplies having selenium concentrations of less than 3.1, 1.7, 189, and 496 micrograms/liter were selected for study. Samples of blood, urine, and tap water were obtained from participants in each community and analyzed for selenium content. Blood samples were also analyzed for glutathione peroxidase activity. Results showed an increase in selenium concentration in the urine as the water selenium increased. Selenium concentrations in blood did not reflect the increased selenium exposure. Glutathione peroxidase activity in whole blood decreased in highly exposed participants compared to those with low exposure. We conclude that glutathione peroxidase activity in cases of possible environmental toxic exposures will not show the increased activity seen in supplementation of selenium to deficient subjects.

  4. Influence of whole wheat inclusion and a blend of essential oils on the performance, nutrient utilisation, digestive tract development and ileal microbiota profile of broiler chickens.

    PubMed

    Amerah, A M; Péron, A; Zaefarian, F; Ravindran, V

    2011-02-01

    1. The aim of the present experiment was to examine the influence of whole wheat inclusion and a blend of essential oils (EO; cinnamaldehyde and thymol) supplementation on the performance, nutrient utilisation, digestive tract development and ileal microbiota profile of broiler chickens. 2. The experimental design was a 2 × 2 factorial arrangement of treatments evaluating two wheat forms (ground wheat [GW] and whole wheat [WW]; 100 and 200 g/kg WW replacing GW during starter [1 to 21 d] and finisher [22 to 35 d] diets respectively) and two levels of EO inclusion (0 or 100 g/tonne diet). All dietary treatments were supplemented with 2000 xylanase units/kg feed. Broiler starter and finisher diets based on wheat and soybean meal were formulated and each diet fed ad libitum to 6 pens of 8 male broilers. 3. During the trial period (1-35 d), wheat form had no significant effect on weight gain or feed intake. However, WW inclusion tended (P = 0.06) to improve feed per gain. Essential oil supplementation significantly improved weight gain in both diets, but the improvements were greater in the GW diet as indicated by a significant wheat form × EO interaction. 4. Main effects of wheat form and EO on the relative weight, length and digesta content of various segments of the digestive tract were not significant. Significant interactions, however, were found for relative gizzard and caecal weights. Essential oil supplementation significantly increased the relative gizzard weight and lowered relative caecal weight in birds fed on the GW based diet, but had no effect in those fed on the WW based diet. 5. Whole wheat inclusion and EO supplementation significantly improved apparent ileal nitrogen digestibility. Apparent ileal digestible energy was not significantly influenced by the dietary treatments. 6. Ileal microbiota profiling, using denaturing gradient gel electrophoresis, showed that the ileal microbiota composition was influenced by feed form. The mean numbers of bacterial species in the ileal contents of birds fed on the GW diet supplemented with EO tended (P = 0.07) to be higher than those of the ileal contents of birds fed on unsupplemented GW based diet. 7. The present data suggested that dietary addition of EO improves broiler weight gain and ileal nitrogen digestibility both in GW and WW based diets, but that the magnitude of the response to EO for weight gain was greater in GW based diet. Whole wheat feeding was found to be beneficial in terms of feed efficiency. PMID:21337207

  5. Archaeal lipid mucosal vaccine adjuvant and delivery system.

    PubMed

    Patel, Girishchandra B; Chen, Wangxue

    2010-04-01

    Archaeal polar lipids are being evaluated as adjuvants/vaccine delivery systems for mucosal vaccines that can provide protection against pathogens that enter the human host via the mucosal surfaces. Archaeosomes, liposomes made from polar lipids extracted from Archaea, with encapsulated antigens elicit strong antigen-specific systemic immune responses upon systemic or intranasal immunization, but fail to generate mucosal immune responses. However, intranasal immunization of mice with the archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) system, obtained by the interaction of archaeosomes/antigens with multivalent cations, induces robust, antigen-specific IgA responses in nasal and vaginal mucosa, feces, bile, and serum. In addition, strong antigen-specific systemic antibody (serum IgG, IgG(1) and IgG(2a)) and cell-mediated responses, including CD8(+) cytotoxic T lymphocyte, are generated. The responses are sustained over time and are subject to good memory-boost responses. The AMVAD formulations are stable during storage, have a good safety profile and show protective efficacy in a murine model of infection/challenge. PMID:20370552

  6. Palifermin: new drug. Prevention of oral mucositis: inappropriate evaluation.

    PubMed

    2007-08-01

    (1) Patients treated with high-dose chemotherapy combined with total body irradiation (myeloablative therapy) often develop oral mucositis. Prevention is based mainly on sucking ice during chemotherapy. (2) Palifermin is a growth factor marketed for the prevention of severe oral mucositis in adults with malignant haemopathies who are receiving myeloablative therapy followed by peripheral stem cell autografting. (3) Palifermin has not been compared with sucking ice, despite the efficacy of this simple treatment. (4) In a randomised placebo-controlled double-blind trial involving 212 adult patients treated with high-dose chemotherapy and total body irradiation, palifermin reduced the incidence of severe oral mucositis (63% versus 98%) and its duration (about 3 days versus 9 days). The myeloablative regimen used in this trial is not that commonly used in Europe. The efficacy of palifermin during less aggressive regimens, which cause less severe oral mucositis, is not known. (5) The main adverse events noted in clinical trials were erythema and cutaneous oedema. It is not known whether palifermin increases the long-term risk of cancer. (6) Treatment with palifermin is expensive, 4800.00 euros in France); the optimal dosing schedule is not known and the unit dose chosen by the manufacturer is wastefully large. (7) In practice, it remains to be demonstrated that palifermin is more effective than simply sucking ice. PMID:17724832

  7. 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

  8. Photobiomodulation reduces oral mucositis by modulating NF-kB

    NASA Astrophysics Data System (ADS)

    Curra, Marina; Pellicioli, Ana Carolina Amorim; Filho, Nélson Alexandre Kretzmann; Ochs, Gustavo; Matte, Úrsula; Filho, Manoel Sant'Ana; Martins, Marco Antonio Trevizani; Martins, Manoela Domingues

    2015-12-01

    The aim of this study was to evaluate NF-kB during 5-fluorouracil (FU)-induced oral mucositis and ascertain whether photobiomodulation (PBM), as a preventive and/or therapeutic modality, influences this transcription factor. Ninety-six male golden Syrian hamsters were allocated into four groups: control (no treatment); PBM therapeutic, PBM preventive, and PBM combined. Animals received an injection of 5-FU on days 0 and 2. On days 3 and 4, the buccal mucosa was scratched. Irradiation was carried out using a 660-nm, 40-mW diode laser at 6 J/cm2 during 6 s/point, 0.24 J/point, for a total dose of 1.44 J/day of application. Animals were euthanized on days 0, 5, 10, and 15 (n=6). Buccal mucosa was removed for protein quantification by Western blot. Clinical analysis revealed that PBM groups exhibited less mucositis than controls on day 10. Control animals exhibited lower levels of NF-kB during mucositis development and healing. The preventive and combined protocols were associated with higher NF-kB levels at day 5; however, the therapeutic group had higher levels at days 10 and 15. These findings suggest that the preventive and/or therapeutic PBM protocols reduced the severity of oral mucositis by activating the NF-kB pathway.

  9. Pharmacological Protection From Radiation {+-} Cisplatin-Induced Oral Mucositis

    SciTech Connect

    Cotrim, Ana P.; Yoshikawa, Masanobu; Sunshine, Abraham N.; Zheng Changyu; Sowers, Anastasia L.; Thetford, Angela D.; Cook, John A.; Mitchell, James B.; Baum, Bruce J.

    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.

  10. Canine gastric mucosal vasodilation with prostaglandins and histamine analogs

    SciTech Connect

    Gerber, J.G.; Nies, A.S.

    1982-10-01

    The effect of direct intragastric artery infusion of prostaglandins E2 and I2, arachidonic acid, dimaprit (histamine H2 agonist), and 2',2'-pyridylethylamine (histamine H1 agonist) on gastric mucosal blood flow was examined in dogs to elucidate the relationship between gastric secretory state and mucosal blood flow in dogs. These compounds were chosen because of their diverse effect on gastric acid secretion. Gastric fundus blood flow was measured both electromagnetically with a flow probe around the left gastric artery which supplies the fundus almost exclusively, and by the radioactive microsphere technique. Intraarterial infusion of all the compounds resulted in gastric mucosal vasodilation even though PGE2, PGI2, and arachidonic acid inhibit gastric acid secretion, dimaprit stimulated gastric acid secretion, and 2',2'-pyridylethylamine does not affect gastric acid secretion. There was total agreement in the blood flow measurements by the two different techniques. Our data suggest that gastric acid secretion and gastric vasodilation are independently regulated. In addition, the validity of the studies in which the aminopyrine clearance indicates that prostaglandins are mucosal vasoconstrictors needs to be questioned because of the reliance of those measurements on the secretory state of the stomach.

  11. Mucosal damage and neutropenia are required for Candida albicans dissemination.

    PubMed

    Koh, Andrew Y; Köhler, Julia R; Coggshall, Kathleen T; Van Rooijen, Nico; Pier, Gerald B

    2008-02-01

    Candida albicans fungemia in cancer patients is thought to develop from initial gastrointestinal (GI) colonization with subsequent translocation into the bloodstream after administration of chemotherapy. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but we have hypothesized that both neutropenia and GI mucosal damage are critical for allowing widespread invasive C. albicans disease. We investigated these parameters in a mouse model of C. albicans GI colonization that led to systemic spread after administration of immunosuppression and mucosal damage. After depleting resident GI intestinal flora with antibiotic treatment and achieving stable GI colonization levels of C. albicans, it was determined that systemic chemotherapy with cyclophosphamide led to 100% mortality, whereas selective neutrophil depletion, macrophage depletion, lymphopenia or GI mucosal disruption alone resulted in no mortality. Selective neutrophil depletion combined with GI mucosal disruption led to disseminated fungal infection and 100% mortality ensued. GI translocation and dissemination by C. albicans was also dependent on the organism's ability to transform from the yeast to the hyphal form. This mouse model of GI colonization and fungemia is useful for studying factors of innate host immunity needed to prevent invasive C. albicans disease as well as identifying virulence factors that are necessary for fungal GI colonization and dissemination. The model may also prove valuable for evaluating therapies to control C. albicans infections. PMID:18282097

  12. Infectious salmon anaemia virus (ISAV) mucosal infection in Atlantic salmon.

    PubMed

    Aamelfot, Maria; McBeath, Alastair; Christiansen, Debes H; Matejusova, Iveta; Falk, Knut

    2015-01-01

    All viruses infecting fish must cross the surface mucosal barrier to successfully enter a host. Infectious salmon anaemia virus (ISAV), the causative agent of the economically important infectious salmon anaemia (ISA) in Atlantic salmon, Salmo salar L., has been shown to use the gills as its entry point. However, other entry ports have not been investigated despite the expression of virus receptors on the surface of epithelial cells in the skin, the gastrointestinal (GI) tract and the conjunctiva. Here we investigate the ISAV mucosal infection in Atlantic salmon after experimental immersion (bath) challenge and in farmed fish collected from a confirmed outbreak of ISA in Norway. We show for the first time evidence of early replication in several mucosal surfaces in addition to the gills, including the pectoral fin, skin and GI tract suggesting several potential entry points for the virus. Initially, the infection is localized and primarily infecting epithelial cells, however at later stages it becomes systemic, infecting the endothelial cells lining the circulatory system. Viruses of low and high virulence used in the challenge revealed possible variation in virus progression during infection at the mucosal surfaces. PMID:26490835

  13. 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 ...

  14. 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

  15. Morphology of the mucosal lesion in gluten sensitivity.

    PubMed

    Marsh, M N; Crowe, P T

    1995-06-01

    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. From in-vivo challenges, it has been demonstrated: (i) that all these lesions comprise a dynamically interrelated series of events, culminating in the severe flat-destructive lesion; and (ii) that gluten evokes a dose-responsive infiltration of IELs (CD3+ CD8+ and TCR alpha beta + or gamma delta +) into the epithelium. Apart from that, little is known of the functions of IELs; it is possible they may have little to do with the evolving mucosal pathology of gluten sensitivity. Increasing work seems to support a view, proposed from this laboratory over 10 years ago, that the immune-mediated responses in jejunal tissue in gluten sensitivity arise in the lamina propria, in association with DR+ macrophages and an abundance of CD4(+)-activated lymphocytes. Many other inflammatory consequences flow from these interactions, involving activation of mast cells, eosinophils and neutrophils, elaboration of cytokines and other products of inflammation, and increased hyperpermeability of the microvasculature with upregulation of adhesion molecules. The result is a doubling of lamina propria volumes in the severe flat lesion. Evidence is also given to show that measurable changes in lamina propria inflammation occur with the infiltrative-hyperplastic lesion. Symptomatology is not related to the degree of proximal mucosal pathology, but to the extent of the mucosal lesion. Data, although scanty, suggests that lesional pathology involves only 30-50% of the entire small bowel mucosa. Thus, most patients, irrespective of proximal mucosal damage, have latent (or asymptomatic) gluten sensitivity. Symptom development requires additional environmental triggers, of which infection is a major contributor. It should also be noted that, while these various environmental triggers may precipitate symptomatology, they do not advance the severity of the mucosal lesion. PMID:7549028

  16. Effects of landfill leachate effluent and bisphenol A on glutathione and glutathione-related enzymes in the gills and digestive glands of the freshwater snail Bellamya purificata.

    PubMed

    Li, Xiangli; Lin, Li; Luan, Tiangang; Yang, Lihua; Lan, Chongyu

    2008-02-01

    Environmental contaminants with estrogenic activity have recently attracted attention due to their potential detrimental effects on the reproduction of human and wildlife. The aim of this study was to evaluate the use of endogenous glutathione and glutathione-related enzymes as biomarkers of exposure to landfill leachate effluent and bisphenol A (BPA) in the freshwater snail, Bellamya purificata. Following exposure to 1%, 5% and 10% landfill leachate effluent and 1, 10, 50 and 100mugl(-1) BPA for 0, 2, 7 and 15d, activities of glutathione S-transferase (GST), selenium-dependent glutathione peroxidase (SeGPx) and glutathione reductase (GR) and levels of total glutathione were measured in the gills and digestive glands of the snails. GST and total glutathione were the most sensitive parameters in both exposure scenarios. GST activities increased by about 80%, while total glutathione decreased to 70% and 80% in the gills and digestive glands, respectively. In contrast, SeGPx and GR activities remained at the same levels in all the treatment groups compared with those of controls. The results indicated that among glutathione and glutathione-related enzymes, GST activity and total glutathione level, which showed dose-dependent dynamics, could be used as biomarkers of aquatic ecosystems contaminated with landfill leachate. PMID:17881034

  17. Glutathione, glutathione disulfide, and S-glutathionylated proteins in cell cultures.

    PubMed

    Giustarini, Daniela; Galvagni, Federico; Tesei, Anna; Farolfi, Alberto; Zanoni, Michele; Pignatta, Sara; Milzani, Aldo; Marone, Ilaria M; Dalle-Donne, Isabella; Nassini, Romina; Rossi, Ranieri

    2015-12-01

    The analysis of the global thiol-disulfide redox status in tissues and cells is a challenging task since thiols and disulfides can undergo artificial oxido-reductions during sample manipulation. Because of this, the measured values, in particular for disulfides, can have a significant bias. Whereas this methodological problem has already been addressed in samples of red blood cells and solid tissues, a reliable method to measure thiols and disulfides in cell cultures has not been previously reported. Here, we demonstrate that the major artifact occurring during thiol and disulfide analysis in cultured cells is represented by glutathione disulfide (GSSG) and S-glutathionylated proteins (PSSG) overestimation, due to artificial oxidation of glutathione (GSH) during sample manipulation, and that this methodological problem can be solved by the addition of N-ethylmaleimide (NEM) immediately after culture medium removal. Basal levels of GSSG and PSSG in different lines of cultured cells were 3-5 and 10-20 folds higher, respectively, when the cells were processed without NEM. NEM pre-treatment also prevented the artificial reduction of disulfides that occurs during the pre-analytical phase when cells are exposed to an oxidant stimulus. In fact, in the absence of NEM, after medium removal, GSH, GSSG and PSSG levels restored their initial values within 15-30min, due to the activity of reductases and the lack of the oxidant. The newly developed protocol was used to measure the thiol-disulfide redox status in 16 different line cells routinely used for biomedical research both under basal conditions and after treatment with disulfiram, a thiol-specific oxidant (0-200?M concentration range). Our data indicate that, in most cell lines, treatment with disulfiram affected the levels of GSH and GSSG only at the highest concentration. On the other hand, PSSG levels increased significantly also at the lower concentrations of the drug, and the rise was remarkable (from 100 to 1000 folds at 200?M concentration) and dose-dependent for almost all the cell lines. These data support the suitability of the analysis of PSSG in cultured cells as a biomarker of oxidative stress. PMID:26476010

  18. Developments in the production of mucosal antibodies in plants.

    PubMed

    Vasilev, Nikolay; Smales, C Mark; Schillberg, Stefan; Fischer, Rainer; Schiermeyer, Andreas

    2016-01-01

    Recombinant mucosal antibodies represent attractive target molecules for the development of next generation biopharmaceuticals for passive immunization against various infectious diseases and treatment of patients suffering from mucosal antibody deficiencies. As these polymeric antibodies require complex post-translational modifications and correct subunit assembly, they are considered as difficult-to-produce recombinant proteins. Beside the traditional, mammalian-based production platforms, plants are emerging as alternative expression hosts for this type of complex macromolecule. Plant cells are able to produce high-quality mucosal antibodies as shown by the successful expression of the secretory immunoglobulins A (IgA) and M (IgM) in various antibody formats in different plant species including tobacco and its close relative Nicotiana benthamiana, maize, tomato and Arabidopsis thaliana. Importantly for biotherapeutic application, transgenic plants are capable of synthesizing functional IgA and IgM molecules with biological activity and safety profiles comparable with their native mammalian counterparts. This article reviews the structure and function of mucosal IgA and IgM antibodies and summarizes the current knowledge of their production and processing in plant host systems. Specific emphasis is given to consideration of intracellular transport processes as these affect assembly of the mature immunoglobulins, their secretion rates, proteolysis/degradation and glycosylation patterns. Furthermore, this review provides an outline of glycoengineering efforts that have been undertaken so far to produce antibodies with homogenous human-like glycan decoration. We believe that the continued development of our understanding of the plant cellular machinery related to the heterologous expression of immunoglobulins will further improve the production levels, quality and control of post-translational modifications that are 'human-like' from plant systems and enhance the prospects for the regulatory approval of such molecules leading to the commercial exploitation of plant-derived mucosal antibodies. PMID:26626615

  19. Application of a spontaneously closed protective stoma in an ileal pouch-anal anastomosis: a preliminary study

    PubMed Central

    Wang, Jinhai; Ke, Bingxin; Lin, Jianjiang; Xu, Jiahe; Chen, Wenbin

    2015-01-01

    Background: To evaluate the application value of a spontaneously closed protective stoma (SCPS) in an ileal pouch-anal anastomosis, which is a novel procedure first performed in our hospital in 2008. Materials and methods: Two males cases with ulcerative colitis and one female with familial adenomatous polyposis were treated with colorectal surgery at the First Affiliated Hospital of Zhejiang University since March 2010. The surgery was designed as total proctocolectomy with an ileal pouch-anal anastomosis and SCPS. The surgical plan and procedure was determined with the patients after analyzing their hospitalized records and follow-up information. Results: No operation-induced death or anastomotic leakage occurred. One patient had a persistent fever and another patient presented with postoperative urinary retention. The average time until flatulence occurred post-SCPS was 26 days, and the average time until the removal of the postoperative stomal tube was 46 days that healed well. Conclusions: An SCPS can effectively protect the anastomosis with a simple operation and avoid the second surgery. Patients with ulcerative colitis require a two-stage operation, those who were in poor health and had a long history of hormone treatment even requiring a three-stage operation. However, a one- or two-stage operation could help alleviate pain for patients who require multiple surgeries and reduce economic burden. PMID:25785126

  20. Standardized ileal digestibility of proteins and amino acids in sesame expeller and soya bean meal in weaning piglets.

    PubMed

    Aguilera, A; Reis de Souza, T C; Mariscal-Landn, G; Escobar, K; Montao, S; Bernal, M G

    2015-08-01

    Apparent ileal digestibility (AID) of diets containing sesame expeller (SE) and soya bean meal (SBM) was determined using 15 piglets (Genetiporc()), weaned at 17 0.4 days with average body weight of 6.4 0.7 kg (Fertilis 20 G Performance, Genetiporc(), PIC Mxico, Quertaro, Mxico). Piglets were randomly assigned to three treatments: (i) a reference diet with casein as the sole protein source; (ii) a mixed diet of casein-SE; and (iii) a mixed diet of casein-SBM. The chemical composition of SE and SBM was determined, and AID and standardized ileal digestibility (SID) of crude protein (CP) and amino acids (AAs) were determined for each protein source. SE contained greater quantities of ether extract, neutral detergent fibre, phytic acid, methionine and arginine than SBM. Lysine and proline contents and trypsin inhibitor activity were higher in SBM than in SE. The AID and SID of CP and AA (except for lysine and proline) were similar in SE and SBM. The AID of lysine and proline was higher in SBM than in SE (p < 0.05), and the SID of proline was higher in SE than in SBM (p < 0.05). These findings indicate that SE is an appropriate alternative protein source for early weaned pigs. PMID:25521700

  1. Recurrent Lower Gastrointestinal Bleeding: Ileal GIST Diagnosed by Video Capsule EndoscopyA Case Report and Literature Review

    PubMed Central

    Lamsen, Marie; Coron, Roger; Deliana, Danila; Rangraj, Madhu; Jesmajian, Stephen

    2013-01-01

    Introduction. Gastrointestinal stromal tumor (GIST) in the ileum is an extremely rare cause of recurrent lower gastrointestinal bleeding (GIB). Case Report. An 89-year-old man was admitted with melana. He had extensive PMH of CAD post-CABG/AICD, AAA repair, chronic anemia, myelodysplastic syndrome, lung cancer after resection, and recurrent GIB. Prior EGDs, colonoscopies, and upper device-assisted enteroscopy showed duodenal ulcer, A-V malformation s/p cauterization, and angioectasia. On admission, Hb was 6.0?g/dL. An endoscopic capsule study showed an ulcerated tumor in the ileum. CT showed no distant metastasis. The lesion was resected successfully and confirmed as a high-grade GIST. The patient was discharged with no further bleeding. Discussion. Early diagnosis for patients with ileal GIST is often challenging. Video capsule endoscopy and double balloon enteroscopy could be useful diagnostic tools. Surgical removal is the first line for a resectable GIST. Imatinib has become the standard therapy. Conclusion. This is a unique case of an ileal GIST in a patient with recurrent GIB which was diagnosed by video capsule. Complicated medical comorbidities often lead to a significant delay in diagnosis. Therefore, we recommend that if GIB does not resolve after appropriate treatments for known causes, the alternative diagnosis for occult GIB must be considered, including malignancy such as GIST. PMID:24027646

  2. Comparison of proctocolectomy and ileal pouch-anal anastomosis to colectomy and ileorectal anastomosis in familial adenomatous polyposis.

    PubMed

    Koskenvuo, L; Mustonen, H; Renkonen-Sinisalo, L; Jrvinen, H J; Lepist, A

    2015-06-01

    Prophylactic surgical options for familial adenomatous polyposis (FAP) are either colectomy and ileorectal anastomosis (IRA) or proctocolectomy and ileal pouch-anal anastomosis (IPAA). The aim of this study was to analyse the short-term and long-term outcomes of these two operative techniques. All patients with FAP in Finland have been prospectively recorded in a database since 1963 were retrospectively reviewed in this analysis. Altogether 140 (61%) colectomies with IRA and 88 (39%) proctocolectomies with IPAA have been performed. Complications occurred in 28 (21%) patients after IRA and in 26 (30%) patients after IPAA. There were 15 (11%) severe complications for IRA and 5 (6%) for IPAA. Twenty-one (15%) patients of the IRA group ended up in conventional ileostomy whereas 3 (3.4%) patients of the IPAA group had their ileal reservoir converted to an ileostomy (p = 0.01). Cumulative survival for IRA was lower than for the IPAA (p = 0.03), but if accounting only for operations made after the IPAA era had commenced, there was no significant difference. IPAA was associated with improved long-term survival without an increase in postoperative complications. The risk of death after colectomy and IRA seemed to be predominantly related to the remaining risk of rectal cancer. Therefore, we favour proctocolectomy with IPAA as the prophylactic surgical procedure for FAP with intermediate or severe polyposis. PMID:25504366

  3. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease

    SciTech Connect

    Willing, B.; Halfvarson, J.; Dicksved, J.; Rosenquist, M.; Jarnerot, G.; Engstrand, L.; Tysk, C.; Jansson, J. K

    2008-08-15

    Large inter-individual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease. To reduce variations in exposure during establishment of the gut flora and influence of genotype, we studied the mucosaassociated microbiota of monozygotic twin pairs that were discordant (n=6) or concordant (n=4) for Crohn's disease. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing and quantitative real-time PCR. The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal Crohn's had a dramatically lower abundance (P<0.001) of Faecalibacterium prausnitzii and increased abundance (P<0.03) of Escherichia coli compared to healthy co-twins and those with Crohn's localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype. The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal Crohn's disease phenotype, distinct from colonic Crohn's disease and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of Crohn's and eventually customized treatment.

  4. Malignant Peripheral Nerve Sheath Tumour of Small Intestine Presenting as Ileo-Ileal Intussusception - A Rare Tumour with Unusual Complication

    PubMed Central

    Pandey, Diwakar; Akhtar, Azaz; Arsia, Ashish; Singh, Nain

    2015-01-01

    Malignant Peripheral Nerve Sheath Tumours (MPNST) arises from a peripheral nerve or exhibit nerve sheath differentiation on histology. Proximal portions of the upper and lower extremities and the trunk are the most common sites of occurrence. Around 50% are associated with Neurofibromatosis Type 1 (NF1) with incidence of two to five per cent in patients with NF1. The estimated incidence in general population without NF1 is 0.0001% of which gastrointestinal MPNST are extremely rare. A 45-year-old lady without pathological antecedent for NF1 was admitted with pain in right lower abdomen and multiple episodes of vomiting for 3 months. Preoperatively intussusception was diagnosed in the small bowel with USG and CECT abdomen showing characteristic target sign. On laparotomy Ileo-ileal intussusception (proximal ileum telescoping into distal ileum) was found 2 feet proximal to ileo-caecal junction with surrounding inflammed mesentery and presence of intraluminal tumour as lead point. Resection of involved segment of ileum along with its mesentery was done followed by ileo-ileal anastomosis. Histopathology was suggestive of high grade MPNST. Postoperative course and follow up for last 10 month is uneventful. This case is unique in terms of a rare tumour presenting with unusual complication and only one case had been reported so far in western literature. PMID:26155547

  5. Malignant Peripheral Nerve Sheath Tumour of Small Intestine Presenting as Ileo-Ileal Intussusception - A Rare Tumour with Unusual Complication.

    PubMed

    Pandey, Diwakar; Verma, Ankur; Akhtar, Azaz; Arsia, Ashish; Singh, Nain

    2015-05-01

    Malignant Peripheral Nerve Sheath Tumours (MPNST) arises from a peripheral nerve or exhibit nerve sheath differentiation on histology. Proximal portions of the upper and lower extremities and the trunk are the most common sites of occurrence. Around 50% are associated with Neurofibromatosis Type 1 (NF1) with incidence of two to five per cent in patients with NF1. The estimated incidence in general population without NF1 is 0.0001% of which gastrointestinal MPNST are extremely rare. A 45-year-old lady without pathological antecedent for NF1 was admitted with pain in right lower abdomen and multiple episodes of vomiting for 3 months. Preoperatively intussusception was diagnosed in the small bowel with USG and CECT abdomen showing characteristic target sign. On laparotomy Ileo-ileal intussusception (proximal ileum telescoping into distal ileum) was found 2 feet proximal to ileo-caecal junction with surrounding inflammed mesentery and presence of intraluminal tumour as lead point. Resection of involved segment of ileum along with its mesentery was done followed by ileo-ileal anastomosis. Histopathology was suggestive of high grade MPNST. Postoperative course and follow up for last 10 month is uneventful. This case is unique in terms of a rare tumour presenting with unusual complication and only one case had been reported so far in western literature. PMID:26155547

  6. Role of Meprins to Protect Ileal Mucosa of Crohn's Disease Patients from Colonization by Adherent-Invasive E. coli

    PubMed Central

    Vazeille, Emilie; Chambon, Christophe; Becker-Pauly, Christoph; Pender, Sylvia L. F.; Jakob, Christine; Müller, Stefan; Lottaz, Daniel; Darfeuille-Michaud, Arlette

    2011-01-01

    Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to adhere to and invade intestinal epithelial cells (IEC), and to survive within macrophages. The interaction of AIEC with IEC depends on bacterial factors mainly type 1 pili, flagella, and outer membrane proteins. In humans, proteases can act as host defence mechanisms to counteract bacterial colonization. The protease meprin, composed of multimeric complexes of the two subunits alpha and beta, is abundantly expressed in IECs. Decreased levels of this protease correlate with the severity of the inflammation in patients with inflammatory bowel disease. The aim of the present study was to analyze the ability of meprin to modulate the interaction of AIEC with IECs. In patients with ileal CD we observed decreased levels of meprins, in particular that of meprin β. Dose-dependent inhibition of the abilities of AIEC strain LF82 to adhere to and invade intestinal epithelial T84 cells was observed when bacteria were pre-treated with both exogenous meprin α and meprin β. Dose-dependent proteolytic degradation of type 1 pili was observed in the presence of active meprins, but not with heat-inactivated meprins, and pretreatment of AIEC bacteria with meprins impaired their ability to bind mannosylated host receptors and led to decreased secretion of the pro-inflammatory cytokine IL-8 by infected T84 cells. Thus, decreased levels of protective meprins as observed in CD patients may contribute to increased AIEC colonization. PMID:21698174

  7. An exploration of the microrheological environment around the distal ileal villi and proximal colonic mucosa of the possum (Trichosurus vulpecula)

    PubMed Central

    Lim, Y. F.; Williams, M. A. K.; Lentle, R. G.; Janssen, P. W. M.; Mansel, B. W.; Keen, S. A. J.; Chambers, P.

    2013-01-01

    Multiple particle-tracking techniques were used to quantify the thermally driven motion of ensembles of naked polystyrene (0.5 m diameter) microbeads in order to determine the microrheological characteristics around the gut mucosa. The microbeads were introduced into living ex vivo preparations of the wall of the terminal ileum and proximal colon of the brushtail possum (Trichosurus vulpecula). The fluid environment surrounding both the ileal villi and colonic mucosa was heterogeneous; probably comprising discrete viscoelastic regions suspended in a continuous Newtonian fluid of viscosity close to water. Neither the viscosity of the continuous phase, the elastic modulus (G) nor the sizes of viscoelastic regions varied significantly between areas within 20 m and areas more than 20 m from the villous mucosa nor from the tip to the sides of the villous mucosa. The viscosity of the continuous phase at distances further than 20 m from the colonic mucosa was greater than that at the same distance from the ileal villous mucosa. Furthermore, the estimated sizes of viscoelastic regions were significantly greater in the colon than in the ileum. These findings validate the sensitivity of the method and call into question previous hypotheses that a contiguous layer of mucus envelops all intestinal mucosa and restricts diffusive mass transfer. Our findings suggest that, in the terminal ileum and colon at least, mixing and mass transfer are governed by more complex dynamics than were previously assumed, perhaps with gel filtration by viscoelastic regions that are suspended in a Newtonian fluid. PMID:23389898

  8. Bacterial stimulation of the TLR-MyD88 pathway modulates the homeostatic expression of ileal Paneth cell ?-defensins.

    PubMed

    Menendez, A; Willing, B P; Montero, M; Wlodarska, M; So, C C; Bhinder, G; Vallance, B A; Finlay, B B

    2013-01-01

    Paneth cell ?-defensins are antimicrobial peptides involved in the control of the intestinal microbiota and immunological homeostasis. In mice, they are encoded by multiple, highly homologous genes (Defa). The transcriptional activity of ileal Defa genes was studied in response to pharmacological and genetic perturbations of the intestinal environment of C57BL/6 mice. Defa gene transcription was sensitive to oral antibiotic administration suggesting that commensal microbes regulate Defa expression. Ileal microbiota analysis showed that decreased transcription of Defa genes correlated with depletion of Lactobacillus. Defa expression was partially restored in vivo by lactobacillus administration to antibiotic-treated mice. Defa transcripts were less abundant in ex vivo, microbiota-free intestinal explants but recovered after explant exposure to UV-killed bacteria, Toll-like receptor (TLR)-2 or TLR4 agonists. Genetic deficiency of several TLRs or MyD88 led to dramatic drops in Defa transcription in vivo. These results show that Paneth cell Defa genes are regulated by commensal bacteria through TLR-MyD88 signaling and provide a further understanding of the dysregulation of intestinal homeostasis that occurs as a result of imbalances in the populations of commensal bacteria. PMID:22986642

  9. The oxido-reductase enzyme glutathione peroxidase 4 (GPX4) governs Salmonella Typhimurium-induced neutrophil transepithelial migration.

    PubMed

    Agbor, Terence A; Demma, Zachary; Mrsny, Randall J; Castillo, Antonio; Boll, Erik J; McCormick, Beth A

    2014-09-01

    Neutrophil (polymorphonuclear leucocytes; PMN) transmigration across mucosal surfaces contributes to dysfunction of epithelial barrier properties, a characteristic underlying many mucosal inflammatory diseases. Using Salmonella enterica serovar Typhimurium (S. Typhimurium) as a prototypic proinflammatory insult, we have previously reported that the eicosanoid hepoxilin A3 (HXA3 ), an endogenous product of 12-lipoxygenase (12-LOX) activity, is secreted from the apical surface of the intestinal epithelium to establish a chemotactic gradient that guides PMN across the epithelial surface. Since little is known regarding the molecular mechanisms that regulate 12-LOX during S. Typhimurium infection, we investigated this pathway. We found that expression of phospholipid glutathione peroxidase (GPX4), which is known to have an inhibitory effect on 12-LOX activity, is significantly decreased at both the mRNA and protein level during infection with S. Typhimurium. Moreover, employing intestinal epithelial cell monolayers expressing siRNA against GPX4 mRNA, S. Typhimurium-induced PMN migration was significantly increased compared with the non-specific siRNA control cells. Conversely, in cells engineered to overexpress GPX4, S. Typhimurium-induced PMN migration was significantly decreased, which is consistent with the finding that partial depletion of GPX4 by RNAi resulted in a significant increase in HXA3 secretion during S. Typhimurium infection. Mechanistically, although we found Salmonella entry not to be required for the induced decrease in GPX4, the secreted effector, SipA, which is known to induce epithelial responses leading to stimulation of HXA3 , governed the decrease in GPX4 in a process that does not lead to an overall increase in the levels of ROS. Taken together, these results suggest that S. Typhimurium induces apical secretion of HXA3 by decreasing the expression of phospholipid GPX, which in turn leads to an increase in 12-LOX activity, and hence HXA3 synthesis. PMID:24617613

  10. Estimation of the standardized ileal digestible lysine requirement for primiparous pregnant sows.

    PubMed

    Shi, M; Shi, C X; Li, Y K; Li, D F; Wang, F L

    2016-04-01

    This experiment was conducted to determine the optimal standardized ileal digestible lysine (SID Lys) level in diets fed to primiparous sows during gestation. A total of 150 (Landrace × Large White) crossbred gilts (weighing 149.9 ± 3.1 kg) were fed gestation diets (12.55 MJ of ME/kg) containing SID Lys levels of 0.43, 0.52, 0.60, 0.70 or 0.80% respectively. Gilts were fed 2.0 kg/day from day 1 to 80 and 3.0 kg/day from day 80 to 110 of gestation respectively. Gilts were allocated to treatments based on their body weight on the day of breeding. Weight gain from day 80 to 110 increased with increasing dietary SID Lys levels (p = 0.044). Fitted broken-line (p = 0.031) and quadratic plot (p = 0.047) analysis of body weight gain indicated that the optimal SID Lys level for primiparous sows was 0.70 and 0.69% respectively. During gestation, neither backfat thickness nor loin eye area was affected by dietary SID Lys level. Increasing dietary Lys had no effect on the litter size at birth or pigs born alive per litter. Litter weight at birth was not affected by dietary SID Lys level. The litter weight variation at birth quadratically decreased with increasing dietary SID Lys (p = 0.021) and was minimized at 0.70% dietary SID Lys. Gilts fed the 0.70% SID Lys diet had the highest dry matter (p = 0.031) and protein (p = 0.044) content in colostrum. On day 110 of gestation, gilts fed the 0.70% SID Lys diet tended to have the highest serum prolactin (p = 0.085) and serum insulin (p = 0.074) levels. The data demonstrate that the optimal dietary SID Lys was 0.70% for pregnant gilts, which is similar to the recommendation of 0.69% that was estimated by the NRC (2012). PMID:26174182

  11. Requirement of standardized ileal digestible valine to lysine ratio for 8- to 14-kg pigs.

    PubMed

    Soumeh, E A; van Milgen, J; Sloth, N M; Corrent, E; Poulsen, H D; Nørgaard, J V

    2015-08-01

    The objective was to define the Val requirement for weaned piglets in the context of reducing the dietary protein content. A dose-response experiment was conducted to estimate the standardized ileal digestible (SID) Val to Lys ratio required to support the optimum growth of post-weaned piglets. In this study, 96 pigs weighing 8 kg were allotted to one of six dietary treatments (16 pigs for each dietary treatment) and were housed individually. Diets were formulated to provide 0.58, 0.62, 0.66, 0.70, 0.74 and 0.78 SID Val : Lys by adding graded levels of crystalline l-Val to the 0.58 SID Val : Lys diet. Lysine was sub-limiting and supplied 90% of the recommendation (10.95 g SID Lys/kg equal to 11.8 g/kg total Lys). Average daily feed intake (ADFI), average daily gain (ADG) and gain to feed ratio (G : F) were determined during a 14-day period of ad libitum feeding. Blood and urine samples were taken at the end of each week (day 7 and 14 of the experiment) 3 h after feeding the experimental diets. The maximum ADFI and ADG were obtained in pigs fed the 0.78 SID Val : Lys diet; it was not different from the results of pigs fed 0.70 SID Val : Lys diet. The highest G : F was obtained in pigs fed 0.70 SID Val : Lys. The plasma concentration of Val increased linearly (P<0.001) as the dietary SID Val : Lys increased. The increasing dietary Val : Lys also resulted in a linear increase in Cys (P<0.001) and a quadratic increase in Arg (P=0.003), Lys (P=0.05) and Phe (P=0.009). The plasma Gly showed a quadratic decrease (P=0.05) as the dietary Val : Lys increased. Neither plasma nor urinary urea to creatinine ratio was affected by treatment. The minimum SID Val : Lys required to maximize ADFI, ADG and G : F was estimated at 0.67 SID Val : Lys by a broken-line model, and at 0.71 SID Val : Lys by a curvilinear plateau model. The Val deficiency caused a reduction in ADFI, and Val supplementation above the requirement did not impair animal performance. In conclusion, 0.70 SID Val : Lys is suggested as the Val requirement for 8 to 14 kg individually housed pigs. PMID:25951981

  12. Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy

    PubMed Central

    Pasello, Michela; Manara, Maria Cristina; Michelacci, Francesca; Fanelli, Maril; Hattinger, Claudia Maria; Nicoletti, Giordano; Landuzzi, Lorena; Lollini, Pier Luigi; Caccuri, Annamaria; Picci, Piero; Scotlandi, Katia; Serra, Massimo

    2011-01-01

    Recent studies have indicated that targeting glutathione-S-transferase (GST) isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel of 15 drug-sensitive and drug-resistant human osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma cell lines, the efficay of the GST-targeting agent 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) has been assessed and related to GST isoenzymes expression (namely GSTP1, GSTA1, GSTM1, and MGST). NBDHEX showed a relevant in vitro activity on all cell lines, including the drug-resistant ones and those with higher GSTs levels. The in vitro activity of NBDHEX was mostly related to cytostatic effects, with a less evident apoptotic induction. NBDHEX positively interacted with doxorubicin, vincristine, cisplatin but showed antagonistic effects with methotrexate. In vivo studies confirmed the cytostatic efficay of NBDHEX and its positive interaction with vincristine in Ewing's sarcoma cells, and also indicated a positive effect against the metastatisation of osteosarcoma cells. The whole body of evidence found in this study indicated that targeting GSTs in osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma may be an interesting new therapeutic option, which can be considered for patients who are scarcely responsive to conventional regimens. PMID:21673434

  13. Involvement of glutathione and glutathione metabolizing enzymes in human colorectal cancer cell lines and tissues.

    PubMed

    Kim, Areum Daseul; Zhang, Rui; Han, Xia; Kang, Kyoung Ah; Piao, Mei Jing; Maeng, Young Hee; Chang, Weon Young; Hyun, Jin Won

    2015-09-01

    Reduced glutathione (GSH) is an abundant tripeptide present in the majority of cell types. GSH is highly reactive and is often conjugated to other molecules, via its sulfhydryl moiety. GSH is synthesized from glutamic acid, cysteine, and glycine via two sequential ATP?consuming steps, which are catalyzed by glutamate cysteine ligase (GCL) and GSH synthetase (GSS). However, the role of GSH in cancer remains to be elucidated. The present study aimed to determine the levels of GSH and GSH synthetic enzymes in human colorectal cancer. The mRNA and protein expression levels of GSH, the catalytic subunit of GCL (GCLC) and GSS were significantly higher in the following five colon cancer cell lines: Caco?2, SNU?407, SNU?1033, HCT?116, and HT?29, as compared with the normal colon cell line, FHC. Similarly, in 9 out of 15 patients with colon cancer, GSH expression levels were higher in tumor tissue, as compared with adjacent normal tissue. In addition, the protein expression levels of GCLC and GSS were higher in the tumor tissue of 8 out of 15, and 10 out of 15 patients with colon cancer respectively, as compared with adjacent normal tissue. Immunohistochemical analyses confirmed that GCLC and GSS were expressed at higher levels in colon cancer tissue, as compared with normal mucosa. Since GSH and GSH metabolizing enzymes are present at elevated levels in colonic tumors, they may serve as clinically useful biomarkers of colon cancer, and/or targets for anti-colon cancer drugs. PMID:26059756

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

    PubMed

    Aghamohamamdi, Azar; Hosseinimehr, Seyed Jalal

    2016-03-01

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

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

    SciTech Connect

    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 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.

  16. METAL-INDUCED INHIBITION OF GLUTATHIONE S-TRANSFERASES

    EPA Science Inventory

    The glutathione S-transferases comprise a group of multi-functional enzymes involved in the biotransformation/detoxication of a broad spectrum of hydrophobic compounds bearing an electrophilic center. The enzymes facilitate the nucleophilic attack of the -SH group of reduced glut...

  17. Extracellular superoxide provokes glutathione efflux from Escherichia coli cells.

    PubMed

    Smirnova, Galina V; Muzyka, Nadezda G; Ushakov, Vadim Y; Tyulenev, Aleksey V; Oktyabrsky, Oleg N

    2015-10-01

    The aim of the study was to elucidate a possible relationship between transmembrane cycling of glutathione and changes in levels of external superoxide. Exposure of growing Escherichia coli to exogenous reactive oxygen species (ROS) generated by xanthine and xanthine oxidase (XO) stimulates reversible glutathione (GSH) efflux from the cells that is considerably lowered under phosphate starvation. This GSH efflux is prevented by exogenous SOD, partially inhibited by catalase, and is not dependent on the GSH exporter CydDC. The ?-glutamyl transpeptidase (GGT) deficiency completely prevents a return of GSH to the cytoplasm. In contrast to wild-type E. coli, mutants devoid of GGT and glutathione reductase (GOR) show enhanced accumulation of oxidized glutathione in the medium after exposure to xanthine and XO. Under these conditions, sodC, ggt and especially gshA mutants reveal more intensive and prolonged inhibition of growth than wild-type cells. Treatment with XO does not influence E. coli viability, but somewhat increases the number of cells with lost membrane potential. In summary, data obtained here indicate that transmembrane cycling of GSH may be involved in E. coli protection against extracellular ROS and may promote rapid growth recovery. PMID:26257303

  18. Developmental Changes in the Biliary Excretion of Methylmercury and Glutathione

    NASA Astrophysics Data System (ADS)

    Ballatori, Nazzareno; Clarkson, Thomas W.

    1982-04-01

    The long half-time for methylmercury in the neonatal rat is explained by the neonatal liver's inability to secrete the toxin into bile, which in adults is the main route of elimination. The ability to secrete mercury into bile develops between 2 and 4 weeks of age and is correlated with the increasing ability of the developing liver to secrete glutathione into bile.

  19. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  20. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  1. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Glutathione test system. 862.1365 Section 862.1365 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  2. REACTION OF BENZENE OXIDE WITH THIOLS INCLUDING GLUTATHIONE

    EPA Science Inventory

    This study accounts for the observations that the metabolism of benzene is dominated by the formation of phenol. As demonstrated here, the pathway leading to S-phenylmercapturic acid is necessarily minor on account of the low efficiency of benzene oxide capture by glutathione at ...

  3. 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.

  4. 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...

  5. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  6. Rational design of an organometallic glutathione transferase inhibitor

    SciTech Connect

    Ang, W.H.; Parker, L.J.; De Luca, A.; Juillerat-Jeanneret, L.; Morton, C.J.; LoBello, M.; Parker, M.W.; Dyson, P.J.

    2010-08-17

    A hybrid organic-inorganic (organometallic) inhibitor was designed to target glutathione transferases. The metal center is used to direct protein binding, while the organic moiety acts as the active-site inhibitor. The mechanism of inhibition was studied using a range of biophysical and biochemical methods.

  7. The efficacy of sucralfate suspension in the prevention of oral mucositis due to radiation therapy

    SciTech Connect

    Epstein, J.B.; Wong, F.L.W. )

    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.

  8. Dark Agouti rat model of chemotherapy-induced mucositis: establishment and current state of the art.

    PubMed

    Vanhoecke, Barbara; Bateman, Emma; Mayo, Bronwen; Vanlancker, Eline; Stringer, Andrea; Thorpe, Daniel; Keefe, Dorothy

    2015-06-01

    Mucositis is a major oncological problem. The entire gastrointestinal and genitourinary tract and also other mucosal surfaces can be affected in recipients of radiotherapy, and/or chemotherapy. Major progress has been made in recent years in understanding the mechanisms of oral and small intestinal mucositis, which appears to be more prominent than colonic damage. This progress is largely due to the development of representative laboratory animal models of mucositis. This review focuses on the development and establishment of the Dark Agouti rat mammary adenocarcinoma model by the Mucositis Research Group of the University of Adelaide over the past 20 years to characterize the mechanisms underlying methotrexate-, 5-fluorouracil-, and irinotecan-induced mucositis. It also aims to summarize the results from studies using different animal model systems to identify new molecular and cellular markers of mucositis. PMID:25966981

  9. Glutathione level after long-term occupational elemental mercury exposure

    SciTech Connect

    Kobal, Alfred Bogomir Prezelj, Marija; Horvat, Milena; Krsnik, Mladen; Gibicar, Darija; Osredkar, Josko

    2008-05-15

    Many in vitro and in vivo studies have elucidated the interaction of inorganic mercury (Hg) and glutathione. However, human studies are limited. In this study, we investigated the potential effects of remote long-term intermittent occupational elemental Hg vapour (Hg{sup o}) exposure on erythrocyte glutathione levels and some antioxidative enzyme activities in ex-mercury miners in the period after exposure. The study included 49 ex-mercury miners divided into subgroups of 28 still active, Hg{sup o}-not-exposed miners and 21 elderly retired miners, and 41 controls, age-matched to the miners subgroup. The control workers were taken from 'mercury-free works'. Reduced glutathione (GSH) and oxidized disulphide glutathione (GSSG) concentrations in haemolysed erythrocytes were determined by capillary electrophoresis, while total glutathione (total GSH) and the GSH/GSSG ratio were calculated from the determined values. Catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in erythrocytes were measured using commercially available reagent kits, while urine Hg (U-Hg) concentrations were determined by cold vapour atomic absorption (CVAAS). No correlation of present U-Hg levels, GSH, GSSG, and antioxidative enzymes with remote occupational biological exposure indices were found. The mean CAT activity in miners and retired miners was significantly higher (p<0.05) than in the controls. No differences in mean GPx activity among the three groups were found, whereas the mean GR activity was significantly higher (p<0.05) in miners than in retired miners. The mean concentrations of GSH (mmol/g Hb) in miners (13.03{+-}3.71) were significantly higher (p<0.05) than in the control group (11.68{+-}2.66). No differences in mean total GSH, GSSG levels, and GSH/GSSG ratio between miners and controls were found. A positive correlation between GSSG and present U-Hg excretion (r=0.41, p=0.001) in the whole group of ex-mercury miners was observed. The significantly lower GSH level (p<0.05) determined in the group of retired miners (9.64{+-}1.45) seems to be age-related (r=-0.39, p=0.001). Thus, the moderate but significantly increased GSH level, GR and CAT activity in erythrocytes in the subgroup of miners observed in the period after exposure to Hg{sup o} could be an inductive and additive response to maintain the balance between GSH and antioxidative enzymes in interaction with the Hg body burden accumulated during remote occupational exposure, which does not represent a severely increased oxidative stress.

  10. 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

  11. Oral mucosal blood flow following dry ice stimulation in humans.

    PubMed

    Heckmann, J G; Hilz, M J; Hummel, T; Popp, M; Marthol, H; Neundörfer, B; Heckmann, S M

    2000-10-01

    The aim of the current pilot study was to establish a procedure that would allow the investigation of microcirculatory changes in the oral cavity. The authors studied the effects of painful stimulation using dry ice (CO2). To investigate potential regional differences in the change of blood flow, recordings were made for the tongue and at the mucosa of the hard palate, lip, and oral vestibule. The authors investigated 26 patients divided into groups of younger subjects (10 men, 3 women; age range 21-31 y) and older patients (2 men, 11 women; age range 54-74 y). Mucosal blood flow (mBF) was obtained at the hard palate, at the tip of the tongue, on the midline of the oral vestibule, and at the lip. Measurements were made during rest and for 2 minutes after application of dry ice for a 10-second duration, using a pencil-shaped apparatus. Blood pressure, heart rate, cutaneous blood flow, transcutaneous partial pressure of carbon dioxiode (PCO2) and partial pressure of oxygen (PO2) were recorded. Mucosal blood flow increased at all sites in response to application of dry ice (p <0.001), with peak flow at 0.5 minute to 1.5 minutes after onset of stimulation. During the 1.5 minutes to 2 minutes, blood flow decreased at all measurement sites with a tendency to return to baseline. Heart rate, blood pressure, pCO2, PO2, and cutaneous blood flow did not show significant changes. Overall, responses in older patients showed more variance when compared with younger patients. Stimulation by dry ice appears to be an effective, noninvasive, and tolerable means to investigate mucosal blood flow at different mucosal sites. Preliminary data indicate different levels of responsiveness to painful cold stimulation at different sites on the oral and perioral mucosa; particularly, mucosal blood flow response at the tongue was least pronounced. Therefore, assessment of stimulated mucosal blood flow appears to be a promising tool to investigate the pathophysiology of a number of neurologic symptoms, eg, the burning mouth syndrome. PMID:11198489

  12. Glutathione reductase: solvent equilibrium and kinetic isotope effects

    SciTech Connect

    Wong, K.K.; Vanoni, M.A.; Blanchard, J.S.

    1988-09-06

    Glutathione reductase catalyzes the NADPH-dependent reduction of oxidized glutathione (GSSG). The kinetic mechanism is ping-pong, and we have investigated the rate-limiting nature of proton-transfer steps in the reactions catalyzed by the spinach, yeast, and human erythrocyte glutathione reductases using a combination of alternate substrate and solvent kinetic isotope effects. With NADPH or GSSG as the variable substrate, at a fixed, saturating concentration of the other substrate, solvent kinetic isotope effects were observed on V but not V/K. Plots of Vm vs mole fraction of D2O (proton inventories) were linear in both cases for the yeast, spinach, and human erythrocyte enzymes. When solvent kinetic isotope effect studies were performed with DTNB instead of GSSG as an alternate substrate, a solvent kinetic isotope effect of 1.0 was observed. Solvent kinetic isotope effect measurements were also performed on the asymmetric disulfides GSSNB and GSSNP by using human erythrocyte glutathione reductase. The Km values for GSSNB and GSSNP were 70 microM and 13 microM, respectively, and V values were 62 and 57% of the one calculated for GSSG, respectively. Both of these substrates yield solvent kinetic isotope effects greater than 1.0 on both V and V/K and linear proton inventories, indicating that a single proton-transfer step is still rate limiting. These data are discussed in relationship to the chemical mechanism of GSSG reduction and the identity of the proton-transfer step whose rate is sensitive to solvent isotopic composition. Finally, the solvent equilibrium isotope effect measured with yeast glutathione reductase is 4.98, which allows us to calculate a fractionation factor for the thiol moiety of GSH of 0.456.

  13. Prolonged fasting increases glutathione biosynthesis in postweaned northern elephant seals.

    PubMed

    Vzquez-Medina, Jos Pablo; Zenteno-Savn, Tania; Forman, Henry Jay; Crocker, Daniel E; Ortiz, Rudy M

    2011-04-15

    Northern elephant seals experience prolonged periods of absolute food and water deprivation (fasting) while breeding, molting or weaning. The postweaning fast in elephant seals is characterized by increases in the renin-angiotensin system, expression of the oxidant-producing protein Nox4, and NADPH oxidase activity; however, these increases are not correlated with increased oxidative damage or inflammation. Glutathione (GSH) is a potent reductant and a cofactor for glutathione peroxidases (GPx), glutathione-S transferases (GST) and 1-cys peroxiredoxin (PrxVI) and thus contributes to the removal of hydroperoxides, preventing oxidative damage. The effects of prolonged food deprivation on the GSH system are not well described in mammals. To test our hypothesis that GSH biosynthesis increases with fasting in postweaned elephant seals, we measured circulating and muscle GSH content at the early and late phases of the postweaning fast in elephant seals along with the activity/protein content of glutamate-cysteine ligase [GCL; catalytic (GCLc) and modulatory (GCLm) subunits], ?-glutamyl transpeptidase (GGT), glutathione disulphide reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), GST and PrxVI, as well as plasma changes in ?-glutamyl amino acids, glutamate and glutamine. GSH increased two- to four-fold with fasting along with a 40-50% increase in the content of GCLm and GCLc, a 75% increase in GGT activity, a two- to 2.5-fold increase in GR, G6PDH and GST activities