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Sample records for ileal mucosal glutathione

  1. Intestinal barrier function in response to abundant or depleted mucosal glutathione in Salmonella-infected rats

    PubMed Central

    van Ampting, Marleen TJ; Schonewille, Arjan J; Vink, Carolien; Brummer, Robert Jan M; Meer, Roelof van der; Bovee-Oudenhoven, Ingeborg MJ

    2009-01-01

    Background Glutathione, the main antioxidant of intestinal epithelial cells, is suggested to play an important role in gut barrier function and prevention of inflammation-related oxidative damage as induced by acute bacterial infection. Most studies on intestinal glutathione focus on oxidative stress reduction without considering functional disease outcome. Our aim was to determine whether depletion or maintenance of intestinal glutathione changes susceptibility of rats to Salmonella infection and associated inflammation. Rats were fed a control diet or the same diet supplemented with buthionine sulfoximine (BSO; glutathione depletion) or cystine (glutathione maintenance). Inert chromium ethylenediamine-tetraacetic acid (CrEDTA) was added to the diets to quantify intestinal permeability. At day 4 after oral gavage with Salmonella enteritidis (or saline for non-infected controls), Salmonella translocation was determined by culturing extra-intestinal organs. Liver and ileal mucosa were collected for analyses of glutathione, inflammation markers and oxidative damage. Faeces was collected to quantify diarrhoea. Results Glutathione depletion aggravated ileal inflammation after infection as indicated by increased levels of mucosal myeloperoxidase and interleukin-1β. Remarkably, intestinal permeability and Salmonella translocation were not increased. Cystine supplementation maintained glutathione in the intestinal mucosa but inflammation and oxidative damage were not diminished. Nevertheless, cystine reduced intestinal permeability and Salmonella translocation. Conclusion Despite increased infection-induced mucosal inflammation upon glutathione depletion, this tripeptide does not play a role in intestinal permeability, bacterial translocation and diarrhoea. On the other hand, cystine enhances gut barrier function by a mechanism unlikely to be related to glutathione. PMID:19374741

  2. Effect of Hymenolepis nana on the mouse ileal mucosal cells: histochemical studies.

    PubMed

    Sanad, M M; Salem, S A; el-Gamal, R L; Darwish, R A; el-Ridi, A M

    1990-12-01

    Histochemical studies of the ileal mucosal cells of mice experimentally infected with H. nana revealed definite increase in mucous secretions indicating increased activity of the goblet cells in response to mucosal irritation. The activity of acid phosphatase was also increased representing a sort of defence mechanism against the attached worms. The activities of ATP-ase and NADH diaphorase enzymes were decreased indicating disturbance in the metabolic and transport processes and in the absorptive function of the intestinal epithelial cells.

  3. 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

  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. A case of extensive genitourinary tuberculosis: combined augmentation ileo-cystoplasty, ureteric ileal replacement and buccal mucosal graft urethroplasty.

    PubMed

    Singh, Onkar; Gupta, Shilpi Singh; Arvind, Nand Kishore

    2013-09-01

    Genitourinary tuberculosis (GUTB) is the second most common form of extrapulmonary TB after lymph nodes. Advanced GUTB leading to strictures of ureters and urethra, and bladder contracture frequently need surgical management. These are usually treated by ileal replacement of ureter, substitution urethroplasty using buccal mucosal graft (BMG) and augmentation ileo-cystoplasty, respectively. These procedures have been well demonstrated individually but all these three procedures have never been combined as single procedure in the same patient. We report a case of advanced GUTB with ureteric and urethral strictures, and bladder contracture which was treated by the ileal replacement of ureter, augmentation ileo-cystoplasty combined with BMG substitution urethroplasty in a single sitting.

  6. 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

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

    PubMed

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

    2015-01-01

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

  8. Marked Differences in Mucosal Immune Responses Induced in Ileal versus Jejunal Peyer’s Patches to Mycobacterium avium subsp. paratuberculosis Secreted Proteins following Targeted Enteric Infection in Young Calves

    PubMed Central

    Facciuolo, Antonio; Gonzalez-Cano, Patricia; Napper, Scott; Griebel, Philip J.

    2016-01-01

    In cattle, Mycobacterium avium subsp. paratuberculosis infection is primarily mediated through M cells overlying Peyer’s patches (PP) in the ileum. The capacity of M. avium subsp. paratuberculosis to invade ileal PP (IPP) versus discrete PP in the jejunum (JPP) and subsequent differences in mucosal immune responses were investigated. Intestinal segments were surgically prepared in both mid-jejunum, containing two JPPs, and in terminal small intestine containing continuous IPP. M. avium subsp. paratuberculosis (109 CFU) was injected into the lumen of half of each intestinal segment when calves were 10–14 days-old and infection confirmed 1–2 months later by PCR and immunohistochemistry. Thirteen recombinant M. avium subsp. paratuberculosis proteins, previously identified as immunogenic, were used to analyze pathogen-specific B- and T-cell responses in PP and mesenteric lymph nodes. IgA plasma cell responses to 9 of 13 recombinant proteins were detected in JPP but not in IPP. Secretory IgA reacting in ELISA with 9 of the 13 recombinant proteins was detected in luminal contents from both jejunal and ileal segments. These observations support the conclusion that pathogen-specific IgA B cells were induced in JPP but not IPP early after a primary infection. The presence of secretory IgA in intestinal contents is consistent with dissemination of IgA plasma cells from the identified mucosa-associated immune induction sites. This is the first direct evidence for M. avium subsp. paratuberculosis uptake by bovine JPP and for local induction of pathogen-specific IgA plasma cell responses after enteric infection. We also provide evidence that bacterial invasion of IPP, a primary B lymphoid tissue, provides a novel strategy to evade induction of mucosal immune responses. Over 60% of PPs in the newborn calf small intestine is primary lymphoid tissue, which has significant implications when designing oral vaccines or diagnostic tests to detect early M. avium subsp

  9. Nontraumatic terminal ileal perforation

    PubMed Central

    Wani, Rauf A; Parray, Fazl Q; Bhat, Nadeem A; Wani, Mehmood A; Bhat, Tasaduq H; Farzana, Fowzia

    2006-01-01

    Background There is still confusion and controversy over the diagnosis and optimal surgical treatment of non traumatic terminal ileal perforation-a cause of obscure peritonitis. Methods This study was a prospective study aimed at evaluating the clinical profile, etiology and optimal surgical management of patients with nontraumatic terminal ileal perforation. Results There were 79 cases of nontraumatic terminal ileal perforation; the causes for perforation were enteric fever(62%), nonspecific inflammation(26%), obstruction(6%), tuberculosis(4%) and radiation enteritis (1%). Simple closure of the perforation (49%) and end to side ileotransverse anastomosis(42%) were the mainstay of the surgical management. Conclusion Terminal ileal perforation should be suspected in all cases of peritonitis especially in developing countries and surgical treatment should be optimized taking various accounts like etiology, delay in surgery and operative findings into consideration to reduce the incidence of deadly complications like fecal fistula. PMID:16759405

  10. 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, ...

  11. Ileal pouch surgery for ulcerative colitis

    PubMed Central

    Bach, Simon P; Mortensen, Neil J

    2007-01-01

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

  12. 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

  13. 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.

  14. Nod2: A Critical Regulator of Ileal Microbiota and Crohn’s Disease

    PubMed Central

    Sidiq, Tabasum; Yoshihama, Sayuri; Downs, Isaac; Kobayashi, Koichi S.

    2016-01-01

    The human intestinal tract harbors large bacterial community consisting of commensal, symbiotic, and pathogenic strains, which are constantly interacting with the intestinal immune system. This interaction elicits a non-pathological basal level of immune responses and contributes to shaping both the intestinal immune system and bacterial community. Recent studies on human microbiota are revealing the critical role of intestinal bacterial community in the pathogenesis of both systemic and intestinal diseases, including Crohn’s disease (CD). NOD2 plays a key role in the regulation of microbiota in the small intestine. NOD2 is highly expressed in ileal Paneth cells that provide critical mechanism for the regulation of ileal microbiota through the secretion of anti-bacterial compounds. Genome mapping of CD patients revealed that loss of function mutations in NOD2 are associated with ileal CD. Genome-wide association studies further demonstrated that NOD2 is one of the most critical genetic factor linked to ileal CD. The bacterial community in the ileum is indeed dysregulated in Nod2-deficient mice. Nod2-deficient ileal epithelia exhibit impaired ability of killing bacteria. Thus, altered interactions between ileal microbiota and mucosal immunity through NOD2 mutations play significant roles in the disease susceptibility and pathogenesis in CD patients, thereby depicting NOD2 as a critical regulator of ileal microbiota and CD. PMID:27703457

  15. Mucosal vaccines

    PubMed Central

    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

  16. Glutathione Transferases

    PubMed Central

    Dixon, David P.; Edwards, Robert

    2010-01-01

    The 55 Arabidopsis glutathione transferases (GSTs) are, with one microsomal exception, a monophyletic group of soluble enzymes that can be divided into phi, tau, theta, zeta, lambda, dehydroascorbate reductase (DHAR) and TCHQD classes. The populous phi and tau classes are often highly stress inducible and regularly crop up in proteomic and transcriptomic studies. Despite much study on their xenobiotic-detoxifying activities their natural roles are unclear, although roles in defence-related secondary metabolism are likely. The smaller DHAR and lambda classes are likely glutathione-dependent reductases, the zeta class functions in tyrosine catabolism and the theta class has a putative role in detoxifying oxidised lipids. This review describes the evidence for the functional roles of GSTs and the potential for these enzymes to perform diverse functions that in many cases are not “glutathione transferase” activities. As well as biochemical data, expression data from proteomic and transcriptomic studies are included, along with subcellular localisation experiments and the results of functional genomic studies. PMID:22303257

  17. Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis

    PubMed Central

    Bajic, Juliana E; Eden, Georgina L; Lampton, Lorrinne S; Cheah, Ker Y; Lymn, Kerry A; Pei, Jinxin V; Yool, Andrea J; Howarth, Gordon S

    2016-01-01

    AIM To investigate the effects of orally gavaged aqueous rhubarb extract (RE) on 5-fluorouracil (5-FU)-induced intestinal mucositis in rats. METHODS Female Dark Agouti rats (n = 8/group) were gavaged daily (1 mL) with water, high-dose RE (HDR; 200 mg/kg) or low-dose RE (LDR; 20mg/kg) for eight days. Intestinal mucositis was induced (day 5) with 5-FU (150 mg/kg) via intraperitoneal injection. Intestinal tissue samples were collected for myeloperoxidase (MPO) activity and histological examination. Xenopus oocytes expressing aquaporin 4 water channels were prepared to examine the effect of aqueous RE on cell volume, indicating a potential mechanism responsible for modulating net fluid absorption and secretion in the gastrointestinal tract. Statistical significance was assumed at P < 0.05 by one-way ANOVA. RESULTS Bodyweight was significantly reduced in rats administered 5-FU compared to healthy controls (P < 0.01). Rats administered 5-FU significantly increased intestinal MPO levels (≥ 307%; P < 0.001), compared to healthy controls. However, LDR attenuated this effect in 5-FU treated rats, significantly decreasing ileal MPO activity (by 45%; P < 0.05), as compared to 5-FU controls. 5-FU significantly reduced intestinal mucosal thickness (by ≥ 29% P < 0.001) as compared to healthy controls. LDR significantly increased ileal mucosal thickness in 5-FU treated rats (19%; P < 0.05) relative to 5-FU controls. In xenopus oocytes expressing AQP4 water channels, RE selectively blocked water influx into the cell, induced by a decrease in external osmotic pressure. As water efflux was unaltered by the presence of extracellular RE, the directional flow of water across the epithelial barrier, in the presence of extracellular RE, indicated that RE may alleviate water loss across the epithelial barrier and promote intestinal health in chemotherapy-induced intestinal mucositis. CONCLUSION In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal

  18. 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

  19. 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 diagnosis of 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 cm in diameter, a 2-mm perforation was detected in the blind end of the ileal J-pouch. The perforation was repaired primarily and protective 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.

  20. Host responses to persistent Mycobacterium avium subspecies paratuberculosis infection in surgically isolated bovine ileal segments.

    PubMed

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

    2013-02-01

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

  1. Blue collection bag after ileal diversion.

    PubMed

    Hildreth, T A; Cass, A S

    1978-02-01

    Five children with ileal diversions have shown asymptomatic blue staining of the urine collection bags. A tryptophan derivative (indican) in the urine that oxidizes to indigo blue on exposure to air is thought to be the cause of this benign transient phenomenon.

  2. Male issues of the ileal pouch.

    PubMed

    Kani, Haluk T; Shen, Bo

    2015-03-01

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

  3. 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.

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

    PubMed Central

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

    1984-01-01

    The possibility that malabsorbed fat passing through the human ileum exerts an inhibitory feedback control on jejunal motility has been investigated in 24 normal subjects by perfusing the ileum with a fat containing solution designed to produce ileal luminal fat concentrations similar to those in steatorrhoea (30-40 mg/ml). Mean transit times through a 30 cm saline perfused jejunal segment were measured by a dye dilution technique. Thirty minutes after ileal fat perfusion, mean transit times rose markedly to 18.9 +/- 2.5 minutes from a control value of 7.5 +/- 0.9 minutes (n = 5; p less than 0.05). This was associated with an increase in volume of the perfused segment which rose to 175.1 +/- 22.9 ml (control 97.6 +/- 10.3 ml, n = 5; p less than 0.05). Transit times and segmental volumes had returned towards basal values 90 minutes after completing the fat perfusion. Further studies showed that ileal fat perfusion produced a pronounced inhibition of jejunal pressure wave activity, percentage duration of activity falling from a control level of 40.3 +/- 5.0% to 14.9 +/- 2.8% in the hour after ileal perfusion (p less than 0.01). Ileal fat perfusion was associated with marked rises in plasma enteroglucagon and neurotensin, the peak values (218 +/- 37 and 68 +/- 13.1 pmol/l) being comparable with those observed postprandially in coeliac disease. These observations show the existence in man of an inhibitory intestinal control mechanism, whereby ileal fat perfusion inhibits jejunal motility and delays caudal transit of jejunal contents. PMID:6706215

  5. 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%, χ2 = 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%, χ2 = 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

  6. 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.

  7. Alteration of the ileal microbiota of weanling piglets by the growth-promoting antibiotic chlortetracycline.

    PubMed

    Rettedal, Elizabeth; Vilain, Sébastien; Lindblom, Stacy; Lehnert, Kelly; Scofield, Clay; George, Sajan; Clay, Sharon; Kaushik, Radhey S; Rosa, Artur J M; Francis, David; Brözel, Volker S

    2009-09-01

    Antibiotics such as chlortetracycline (CTC) have been used to promote growth of pigs for decades, but concerns over increased antibiotic-resistant infections in humans have prompted the development of alternative strategies. Developing alternatives to antibiotic growth promoters (AGPs) could be informed by information on the mechanisms of growth promotion, notably, how AGPs affect the microbial populations of the gastrointestinal tract. Pigs from three sows were aseptically delivered by cesarean section. Six piglets were distributed to each of two foster mothers until weaning, when piglets were fed a diet with or without 50 mg/kg CTC for 2 weeks. The ileal bacterial microbiota was characterized by using a cultivation-independent approach based on DNA extraction, PCR amplification, cloning, and sequencing of the 16S rRNA gene pool. The ileal and mucosal communities of these growing pigs were dominated by Lactobacillus bacteria, various members of the family Clostridiaceae, and members of the poorly known genus Turicibacter. Overall, CTC treatment resulted in three shifts: a decrease in Lactobacillus johnsonii, an increase in L. amylovorus, and a decrease in Turicibacter phylotypes. The composition of the microbiota varied considerably between individual pigs, as revealed by shared operational taxonomic units (OTUs) and similarity (SONS) analysis (theta(YC) values). While the observed variation between untreated pigs obscured the possible effect of CTC, integral-LIBSHUFF and SONS analyses of pooled libraries indicated a significant shift due to CTC in both the lumen and the mucosa, with some OTUs unique to either treated or control ileum. DOTUR analysis revealed little overlap between control and treated communities at the 3% difference level, indicating unique ileal communities in the presence of CTC.

  8. Ileal Trichobezoar Presenting as Intestinal Obstruction and Peritonitis

    PubMed Central

    Rattan, Kamal Nain; Yadav, Vikas; Singh, Jasbir

    2017-01-01

    Trichobezoar is less common in boys. We are reporting a case of isolated ileal trichobezoars in a 4-year old boy causing intestinal obstruction and gut ischemia with perforation and peritonitis. The case was managed surgically with ileal resection and anastomosis. Postoperative period was uneventful.

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

    PubMed Central

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

    1994-01-01

    In patients with active Crohn's disease and in a control group the fatty acid profiles in the whole lipid fraction of ileal and colonic mucosal biopsy specimens were determined by capillary gas chromatography. The biopsy specimens in Crohn's disease patients were taken from the inflamed terminal ileum as well as from the inflamed and macroscopically normal colon. Compared with controls the fatty acid distribution in the inflamed ileal mucosa was significantly characterised by (a) a decrease of 18:2 n6 and 18:3 n3 accompanied by a substantial increase of the highly polyunsaturated fatty acids 20:4 n6, 22:4 n6, and 22:6 n3 and (b) a higher unsaturation index of total fatty acids compared with controls. These changes were similar in the inflamed colon. Additionally, both the inflamed and the macroscopically normal colonic mucosa showed an increase of saturated (18:0) and a decrease of monounsaturated fatty acids (18:1 n9). Fatty acid profiles of ileum and colon showed side variations in controls, but not in the Crohn's disease group. These data suggest that in Crohn's disease changes in the distribution of polyunsaturated fatty acids seem to be the general feature of inflamed mucosa in small and large intestine. Results further suggest that colonic fatty acid metabolism in Crohn's disease is altered by degrees, showing changes in saturated and monounsaturated fatty acids as an additional, primary event. PMID:7959199

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

    PubMed

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

    2014-08-01

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

  11. Effect of antidiarrheal and antimotility drugs on ileal excreta.

    PubMed

    Kramer, P

    1977-04-01

    Commonly used antimotility and antidiarrheal drugs were administered to six ileostomized subjects to determine whether their normal ileal excreta and that induced by prune juice could be altered. A total of 49 studies were performed, 21 with and 28 without prune juice. Bismuth subgallate was the only drug which significantly reduced the normal ileal excreta (P less than 0.05). Codeine sulfate decreased the ileal excreta in two of three subjects in either type of study. The third subject was a nonresponder to drugs. Deodorized tincture of opium (DTO) and diphenoxylate (Lomotil) were also effective in some subjects. Propantheline, tincture of belladonna, Sorboquel, and Kaopectate did not appear to decrease ileal excreta. Calcium carbonate, on the other hand, increased ileal excreta; fat excretion was also increased.

  12. Oral mucositis - self-care

    MedlinePlus

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

  13. C6, a new monoclonal antibody, reacts with the follicle-associated epithelium of calf ileal Peyer's patches

    PubMed Central

    Tozaki, Kana; Kimura, Junpei; Ryu, Nobuyuki; Nasu, Testuo; Pernthaner, Anton; Hein, Wayne R.

    2013-01-01

    The follicle-associated epithelium (FAE) of Peyer's patches (PPs) contains M cells that are important for reducing mucosal immune responses by transporting antigens into the underlying lymphoid tissue. We generated a monoclonal antibody (C6) that reacted with the FAE of calf ileal PPs, and analyzed the characteristics of C6 using immunohistochemistry and Western blotting. FAE of the ileal PP was stained with C6 during both late fetal developmental and postnatal stages. Neither the villous epithelial cell nor intestinal crypt basal cells were stained at any developmental stage. During the prenatal stages, FAE of the jejunal PP was C6-negative. However, a few C6-positive cells were distributed diffusely in some FAE of the jejunal PPs during the postnatal stages. The protein molecular weight of the antigen recognized by C6 was approximately 45 kDa. These data show that C6 is useful for identifying the FAE in ileal PPs and further suggest that differentiation of the FAE in these areas is independent of external antigens. PMID:23388432

  14. Diabetes and elevated urea level predict for uretero-ileal stricture after radical cystectomy and ileal conduit formation

    PubMed Central

    Hoag, Nathan; Papa, Nathan; Beharry, Bhawanie Koonj; Lawrentschuk, Nathan; Chiu, Danny; Sengupta, Shomik; Bolton, Damien

    2017-01-01

    Introduction Benign uretero-ileal anastomotic stricture is a significant complication following radical cystectomy and ileal conduit urinary diversion after radical cystectomy. We examined risk factors for stricture formation to predict those at greatest stricture risk. Methods A retrospective chart review was conducted for patients undergoing radical cystectomy and ileal conduit diversion between 2002 and 2012. Demographic data and patient variables were analyzed to determine risk factors for uretero-ileal stricture using multivariate logistic regression. Results Over the study period, 133 patients underwent cystectomy and ileal conduit formation, with 14 (10.5%) developing uretero-ileal anastomotic stricture. Diabetes and elevated serum urea level (defined as >7.1 mmol/L) were associated with increased risk for development of uretero-ileal stricture (odds ratio 4.31 and 4.28, respectively; p<0.05 for each). Conclusions In this patient cohort, diabetes and elevated serum urea level were predictive for the development of uretero-ileal anastomotic stricture. Further prospective study with larger patient samples is required. PMID:28360953

  15. 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...

  16. 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

  17. The Features of Fecal and Ileal Mucosa-Associated Microbiota in Dairy Calves during Early Infection with Mycobacterium avium Subspecies paratuberculosis

    PubMed Central

    Derakhshani, Hooman; De Buck, Jeroen; Mortier, Rienske; Barkema, Herman W.; Krause, Denis O.; Khafipour, Ehsan

    2016-01-01

    Current diagnostic tests for Johne's disease (JD), a chronic granulomatous inflammation of the gastrointestinal tract of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), lack the sensitivity to identify infected animals at early (asymptomatic) stages of the disease. The objective was to determine the pattern of MAP-associated dysbiosis of intestinal microbiota as a potential biomarker for early detection of infected cattle. To that end, genomic DNA was extracted from ileal mucosa and fecal samples collected from 28 MAP-positive and five control calves. High-throughput Illumina sequencing of the V4 hypervariable region of the 16S rRNA gene was used for community profiling of ileal mucosa-associated (MAM) or fecal microbiota. The PERMANOVA analysis of unweighted UniFrac distances revealed distinct clustering of ileal MAM (P = 0.049) and fecal microbiota (P = 0.068) in MAP-infected vs. control cattle. Microbiota profile of MAP-infected animals was further investigated by linear discriminant analysis effective size (LEfSe); several bacterial taxa within the phylum Proteobacteria were overrepresented in ileal MAM of control calves. Moreover, based on reconstructed metagenomes (PICRUSt) of ileal MAM, functional pathways associated with MAP infection were inferred. Enrichment of lysine and histidine metabolism pathways, and underrepresentation of glutathione metabolism and leucine and isoleucine degradation pathways in MAP-infected calves suggested potential contributions of ileal MAM in development of intestinal inflammation. Finally, simultaneous overrepresentation of families Planococcaceae and Paraprevotellaceae, as well as underrepresentation of genera Faecalibacterium and Akkermansia in the fecal microbiota of infected cattle, served as potential biomarker for identifying infected cattle during subclinical stages of JD. Collectively, based on compositional and functional shifts in intestinal microbiota of infected cattle, we inferred that

  18. Glutathione in cyanobacteria

    NASA Technical Reports Server (NTRS)

    Bermudes, D.

    1985-01-01

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

  19. 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.

  20. 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 4×3×2.5 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

  1. The effect of PARS inhibition on ileal histopathology, apoptosis and lipid peroxidation in LPS-induced obstructive jaundice.

    PubMed

    Dirlik, Musa; Caglikulekci, Mehmet; Cinel, Ismail; Cinel, Leyla; Tamer, Lülüfer; Pata, Cengiz; Kanik, Arzu; Ocal, Koray; Ogetman, Zekai; Aydin, Süha

    2003-08-01

    In our experimental study, we investigated the protective effect of 3-aminobenzamide (3-AB), the poly (ADP-ribose) synthetase (PARS inhibitor), on the ileal histopathology and the apoptosis in lipopolysaccharide (LPS)-induced inflammation in rats with obstructive jaundice (OJ). We randomized 40 rats into five groups. Group 1: sham group; Group 2: OJ group; Group 3: OJ+LPS; Group 4: OJ+3-AB+LPS; Group 5: OJ+LPS+3-AB. At the fifth day; the rats were jaundiced. In Group 3; 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and then after 6h the rats were sacrificed. In Group 4; 10 mg kg(-1) 3-AB was administrated intraperitoneally at the fifth day and repeated daily for 3 days and at the eighth day, 10 mg kg(-1) LPS was injected intraperitoneally. In Group 5, 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and after 6h 10 mg kg(-1) 3-AB was administrated intraperitoneally and repeated daily for 3 days. At the eighth day, rats were sacrificed. Blood samples were taken for detection of serum MDA levels. Ileum samples were taken after relaparotomy for histopathological examination to evaluate the endotoxin-related intestinal injury and Caspase-3 apoptosis and for detection of tissue MDA and ATPase activities. There was marked destruction of villous and crypt epithelial cells and extensive apoptosis in Groups 3 and 5 in histopathological examination. In Group 4, the scores of intestinal mucosal damage and apoptotic cells were reduced significantly (P<0.05). On the other hand, the scores of intestinal mucosal damage and apoptotic cells were not improved in Group 5. After the administration of 3-AB (Group 4), serum and ileal MDA levels decreased, ileal ATPase increased as compared to Groups 1 and 2. Our study showed that 3-AB prevented the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if it was administrated before LPS. However, 3-AB failed to prevent the mucosal damage and apoptotic loss of intestinal

  2. 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...

  3. Role of the mucous/glycocalyx layers in insulin permeation across the rat ileal membrane.

    PubMed

    Aoki, Yoshinobu; Morishita, Mariko; Takayama, Kozo

    2005-06-13

    The contribution of mucous/glycocalyx layers, as a diffusional or enzymatic barrier, to the absorption of insulin was investigated in situ and in vitro studies using rats. To remove the mucous/glycocalyx layers, ileal segments were exposed to a hyaluronidase solution in situ. The removal of the layers was confirmed by transmission electron microscopy, and the safety of the hyaluronidase pretreatment was established based on light microscopy, a constant mucosal membrane electrical resistance and the absence of lactate dehydrogenase leakage. In the in situ loop absorption experiment, hyaluronidase pretreatment significantly increased the plasma insulin level accompanied by an obvious hypoglycemic response. In the in vitro transport experiment, the apparent permeability coefficient of insulin was significantly increased by the hyaluronidase pretreatment, whereas that of 4.4 kDa fluorescein isothiocyanate-labeled dextran and of antipyrine, respective markers for passive para- and transcellular permeation, was unaffected. In the insulin degradation experiment in vitro, a significant amount of insulin was degraded in the compartment removed by hyaluronidase pretreatment. Thus, the mucous/glycocalyx layers functioned in insulin absorption as an enzymatic barrier and insignificantly affected diffusive absorption. In addition, co-administration of aprotinin, a protease inhibitor, further increased insulin absorption from ileum pretreated with hyaluronidase, implying the existence of another enzymatic barrier that influences insulin mucosal absorption.

  4. Comparison of brush and biopsy sampling methods of the ileal pouch for assessment of mucosa-associated microbiota of human subjects

    PubMed Central

    2014-01-01

    Background Mucosal biopsy is the most common sampling technique used to assess microbial communities associated with the intestinal mucosa. Biopsies disrupt the epithelium and can be associated with complications such as bleeding. Biopsies sample a limited area of the mucosa, which can lead to potential sampling bias. In contrast to the mucosal biopsy, the mucosal brush technique is less invasive and provides greater mucosal coverage, and if it can provide equivalent microbial community data, it would be preferable to mucosal biopsies. Results We compared microbial samples collected from the intestinal mucosa using either a cytology brush or mucosal biopsy forceps. We collected paired samples from patients with ulcerative colitis (UC) who had previously undergone colectomy and ileal pouch anal anastomosis (IPAA), and profiled the microbial communities of the samples by sequencing V4-V6 or V4-V5 16S rRNA-encoding gene amplicons. Comparisons of 177 taxa in 16 brush-biopsy sample pairs had a mean R2 of 0.94. We found no taxa that varied significantly between the brush and biopsy samples after adjusting for multiple comparisons (false discovery rate ≤0.05). We also tested the reproducibility of DNA amplification and sequencing in 25 replicate pairs and found negligible variation (mean R2 = 0.99). A qPCR analysis of the two methods showed that the relative yields of bacterial DNA to human DNA were several-fold higher in the brush samples than in the biopsies. Conclusions Mucosal brushing is preferred to mucosal biopsy for sampling the epithelial-associated microbiota. Although both techniques provide similar assessments of the microbial community composition, the brush sampling method has relatively more bacterial to host DNA, covers a larger surface area, and is less traumatic to the epithelium than the mucosal biopsy. PMID:24529162

  5. Ileal involvement in toxic epidermal necrolysis (Lyell syndrome).

    PubMed

    Michel, P; Joly, P; Ducrotte, P; Hemet, J; Leblanc, I; Lauret, P; Lerebours, E; Colin, R

    1993-10-01

    Intestinal involvement in toxic epidermal necrolysis (TEN) has been identified only rarely. This report describes a case of TEN with ileal manifestations characterized by a profuse diarrhea with malabsorption, protein-losing enteropathy, and radiologically by multiple stenosis. After healing of the cutaneous lesions, total parenteral nutrition was initiated, resulting in a decreased diarrhea. However, after one month of total parenteral nutrition, malabsorption and protein-losing enteropathy continued and the radiological lesions were still present with an aspect consistent with a sclerotic process. A surgical resection of the pathological ileal segment was performed with end-to-end anastomosis. Pathological examination of the resected segment showed a necrosis of the ileal mucosa with a pattern similar to that of the epidermal necrosis. No sclerosis was observed. It seems that a prolonged total parenteral nutrition could have induced a complete healing of intestinal lesions. This case report is the first clinical, radiological, and histological study of an ileal involvement in TEN.

  6. Squamous cell carcinoma of cervix metastatic to ileal loop

    SciTech Connect

    Hulecki, S.J.; Klein, F.A.; Davis, J.E.

    1985-12-01

    A case is presented of squamous cell carcinoma of the cervix with an isolated metastasis to an ileal loop six years after diversion and seven years after definitive treatment of the primary lesion with irradiation.

  7. The influence of copper concentration and source on ileal microbiota.

    PubMed

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

    2009-03-01

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

  8. Validation of a chicken ileal explant culture for measurement of mucosal inflammation induced by lipopolysaccharide

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gut mucosa holds a single layer of epithelial cells and the largest mass of lymphoid tissue in the body. While epithelial cell cultures are widely used to assess intestinal barrier functions, they have limitations to study cellular interactions with other cells, in particular those of the immune sys...

  9. Neutral detergent fiber increases endogenous ileal losses but has no effect on ileal digestibility of amino acids in growing pigs.

    PubMed

    Mariscal-Landín, Gerardo; Reis de Souza, Tércia Cesária; Bayardo Uribe, Alejandro

    2017-02-01

    Two experiments were conducted to determine the effect of neutral detergent fiber (NDF) on endogenous amino acids and protein ileal losses; and also apparent ileal digestibility (AID), and standardized ileal digestibility (SID) of amino acids and crude protein. Sixteen barrows were fed four protein-free diets containing graded NDF levels in Experiment 1. NDF was a mixture of sugarcane bagasse and corn leaves (SBCL). Twenty-four barrows were fed diets with soybean protein concentrate (SPC) or casein as protein sources and SBCL or corncobs (CC) as NDF sources in Experiment 2. In Experiment 1, a linear increase (P < 0.05) in endogenous amino acid and protein ileal losses was observed with increased NDF levels, except for arginine, histidine, methionine and proline. In Experiment 2, protein (P < 0.001) and NDF (P < 0.01) sources significantly affected AID of dry matter, which was higher in casein diets (71.7%) and CC diets (70.7%). Protein and NDF sources significantly affected (P < 0.05) SID of crude protein, which was higher in casein diets (92.8%) and CC diets (92.7%). NDF source had no effect (P > 0.05) on SID of amino acids. Overall, this study showed that NDF increased endogenous amino acid and protein ileal losses, but did not affect ileal digestibility of amino acids.

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

    PubMed

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

    2014-06-24

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

  11. Ileal function in patients with untreated adult coeliac disease.

    PubMed Central

    Silk, D B; Kumar, P J; Webb, J P; Lane, A E; Clark, M L; Dawson, A M

    1975-01-01

    A double-lumen perfusion technique has been used to investigate jejunal and ileal absorption of glucose, water, and electrolytes in a group of patients with untreated adult coeliac disease. Correct positioning of the tube was confirmed by measuring the differential jejunal and ileal handling of bicarbonate. Eight control subjects and eight patients with coeliac disease were perfused with an isotonic electrolyte solution containing 50 mM glucose and 25 mM bicarbonate. The group of coeliac patients had impaired jejunal absorption of glucose (P less than 0.001), water (P less than 0.01), sodium (P less than 0.02), and chloride (P greater than 0.05) compared with the control group. In contrast the group of coeliac patients had normal ileal glucose and water absorption and increased ileal sodium (P greater than 0.01) and chloride (P greater than 0.05) absorption compared with the controls. Evidence for ileal adaptation was found in three individual patients who had absorptive values outside 2SD of the normal mean. The results indicate that the distal small intestine in coeliac disease has the ability to adopt to the damage and loss of absorptive capacity in the proximal small intestine. PMID:1132801

  12. Pathogenesis of Salmonellosis STUDIES OF FLUID SECRETION, MUCOSAL INVASION, AND MORPHOLOGIC REACTION IN THE RABBIT ILEUM

    PubMed Central

    Giannella, R. A.; Formal, S. B.; Dammin, G. J.; Collins, H.

    1973-01-01

    Strains of Salmonella typhimurium were studied in the ligated rabbit ileal loop model to gain insight into the mechanisms whereby bacteria which invade the gastrointestinal mucosa evoke fluid exsorption. The organisms employed differed in various biologic attributes including the ability to invade the ileal epithelium, multiply within the mucosa, elicit an acute inflammatory reaction, and disseminate across the intestinal wall. Some strains provoked small intestinal fluid exsorption although these did not elaborate enterotoxin. Only those strains which invaded the mucosa were accompanied by either mucosal inflammation or fluid exsorption. Noninvasive strains produced neither histologic abnormalities nor fluid secretion. While strains which invaded the mucosa caused an acute inflammatory reaction, not all such strains evoked fluid secretion. Furthermore, there was no correlation in ability of invasive organisms to evoke fluid secretion or in the intensity of mucosal inflammation, number of intramucosal salmonellae, or in ability to disseminate from the rabbit ileum. These observations suggest that, as is the case in shigellosis, mucosal invasion may be a necessary factor for the intestinal fluid loss in salmonellosis. A bacterial property or factor, in addition to invasion of the gastrointestinal mucosa, seems to be responsible for fluid exsorptin. However, it is unlikely that a salmonella enterotoxin comparable to that elaborated by Vibrio cholerae, toxigenic Escherichia coli, or Shigella dysenteriae 1 is related to fluid secretion in salmonellosis. Images PMID:4630603

  13. Ileal microbiota of growing pigs fed different dietary calcium phosphate levels and phytase content and subjected to ileal pectin infusion.

    PubMed

    Metzler-Zebeli, B U; Vahjen, W; Baumgärtel, T; Rodehutscord, M; Mosenthin, R

    2010-01-01

    Two experiments with growing pigs were conducted to determine the effects of dietary P and Ca levels, phytase supplementation, and ileal pectin infusion on changes in bacterial populations in the ileum and on ileal and fecal fermentation patterns. Growing pigs (BW 30.1 +/- 1.3 kg) were fitted with simple T-cannulas at the distal ileum and were fed a low-P corn-soybean meal control diet (3 g of P/kg), or the control diet supplemented with either 15 g of monocalcium phosphate (MCP)/kg (Exp. 1) or 1,000 phytase units of phytase/kg (Exp. 2). Daily infusion treatments consisted of either 60 g of pectin dissolved in 1.8 L of demineralized water or 1.8 L of demineralized water as a control infusion, infused via the ileal cannula. In each experiment, 8 barrows were assigned to 4 dietary treatments according to a double incomplete 4 x 2 Latin square design. The dietary treatments in Exp. 1 were the control diet with water infusion, the control diet with pectin infusion, the MCP diet with water infusion, or the MCP diet with pectin infusion. In Exp. 2, the pigs received the same control treatments as in Exp. 1 and the phytase diet in combination with water or pectin infusion. Gene copy numbers of total bacteria, Lactobacillus spp., Lactobacillus reuteri, Lactobacillus amylovorus/Lactobacillus sobrius, Lactobacillus mucosae, Enterococcus spp., Enterococcus faecium, Enterococcus faecalis, bifidobacteria, the Clostridium coccoides cluster, the Clostridium leptum cluster, the Bacteroides-Prevotella-Porphyrmonas group, and Enterobacteriaceae were determined by quantitative PCR in DNA extracts of ileal digesta. In Exp. 1, addition of MCP reduced ileal gene copy numbers of Enterococcus spp. (P = 0.048), E. faecium (P = 0.015), and the C. leptum cluster (P = 0.028), whereas pectin infusion enhanced (P = 0.008) ileal d-lactate concentration. In Exp. 2, supplemental phytase led to greater ileal gene copy numbers of the C. coccoides (P = 0.041) and C. leptum (P = 0.048) clusters and

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

    PubMed

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

    2015-09-15

    Transforming growth factor (TGF)-β-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(α)1 mRNA levels compared with control IMF. TGF-β1 promoted pTAK1 nuclear translocation and collagen synthesis. TAK1 inhibition or silencing significantly reduced TGF-β1-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.

  15. Endoscopic Treatment of Stump Leakage Related to the Ileal Conduit

    PubMed Central

    Odemis, Bulent; Oztas, Erkin; Akpinar, Muhammet Yener; Olcucuoglu, Erkan; Kayacetin, Ertugrul

    2016-01-01

    Abstract Background: Ileal conduit with leakage from either the anastomotic site or the stump is associated with high morbidity and mortality rates. The standard treatment of stump leakage is surgery. Case Presentation: A 60-year-old male patient was admitted to our hospital with complaint of hematuria and bladder carcinoma was diagnosed. After performing radical cystectomy and ileal conduit, he developed fever with abdominal pain within the first week of surgery. Stump leakage was diagnosed by endoscopic examination performed through a gastroscope. After two over-the-scope clips (OTSCs) were applied to the stump, vinyl mesh was inserted into the space between the OTSCs. Later, cyanoacrylat and lipiodol were repelled on the OTSCs and vinyl mesh. Subsequently, stump leakage was resolved. Conclusion: This is the first case of stump leakage related to ileal conduit that has been treated endoscopically, according to the current literature. PMID:27579432

  16. Tracking (Poly)phenol components from raspberries in ileal fluid.

    PubMed

    McDougall, Gordon J; Conner, Sean; Pereira-Caro, Gema; Gonzalez-Barrio, Rocio; Brown, Emma M; Verrall, Susan; Stewart, Derek; Moffet, Tanya; Ibars, Maria; Lawther, Roger; O'Connor, Gloria; Rowland, Ian; Crozier, Alan; Gill, Chris I R

    2014-07-30

    The (poly)phenols in ileal fluid after ingestion of raspberries were analyzed by targeted and nontargeted LC-MS(n) approaches. Targeted approaches identified major anthocyanin and ellagitannin components at varying recoveries and with considerable interindividual variation. Nontargeted LC-MS(n) analysis using an orbitrap mass spectrometer gave exact mass MS data which were sifted using a software program to select peaks that changed significantly after supplementation. This method confirmed the recovery of the targeted components but also identified novel raspberry-specific metabolites. Some components (including ellagitannin and previously unidentified proanthocyanidin derivatives) may have arisen from raspberry seeds that survived intact in ileal samples. Other components include potential breakdown products of anthocyanins, unidentified components, and phenolic metabolites formed either in the gut epithelia or after absorption into the circulatory system and efflux back into the gut lumen. The possible physiological roles of the ileal metabolites in the large bowel are discussed.

  17. 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

  18. Moderate dietary protein restriction alters the composition of gut microbiota and improves ileal barrier function in adult pig model

    PubMed Central

    Fan, Peixin; Liu, Ping; Song, Peixia; Chen, Xiyue; Ma, Xi

    2017-01-01

    This study was conducted to investigate impacts of dietary protein levels on gut bacterial community and gut barrier. The intestinal microbiota of finishing pigs, fed with 16%, 13% and 10% crude protein (CP) in diets, respectively, were investigated using Illumina MiSeq sequencing. The ileal bacterial richness tended to decrease when the dietary protein concentration reduced from 16% to 10%. The proportion of Clostridium_sensu_stricto_1 in ileum significantly decreased, whereas Escherichia-Shigella increased with reduction of protein concentration. In colon, the proportion of Clostridium_sensu_stricto_1 and Turicibacter increased, while the proportion of RC9_gut_group significantly decreased with the dietary protein reduction. Notably, the proportion of Peptostreptococcaceae was higher in both ileum and colon of 13% CP group. As for metabolites, the intestinal concentrations of SCFAs and biogenic amines decreased with the dietary protein reduction. The 10% CP dietary treatment damaged ileal mucosal morphology, and decreased the expression of biomarks of intestinal cells (Lgr5 and Bmi1), whereas the expression of tight junction proteins (occludin and claudin) in 13% CP group were higher than the other two groups. In conclusion, moderate dietary protein restriction (13% CP) could alter the bacterial community and metabolites, promote colonization of beneficial bacteria in both ileum and colon, and improve gut barrier function. PMID:28252026

  19. Mucosal melanoma: an update.

    PubMed

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

    2015-03-01

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

  20. Impairment of 'ileostomy adaptation' in patients after ileal resection.

    PubMed

    Hill, G L; Mair, W S; Goligher, J C

    1974-12-01

    Ileostomists claim that in the months following the establishment of an ileostomy, the faecal output decreases in volume and becomes less fluid. It is claimed that this ;ileostomy adaptation' does not occur in those patients who have had an ileal resection. To determine whether ileostomy adaptation does occur and to examine its physiological mechanisms, 10 ileostomy patients were studied. Five had had ileal resection and five had not. The output of fluid, sodium, and potassium from the ileostomy was studied in each patient for the first 11 days after ileostomy and again at six months. Those patients in whom the terminal ileum was preserved had small faecal outputs of fluid and sodium from the outset, and the water content of the effluent was significantly less at six months. After rapid expansion of the extracellular fluid by intravenous saline, there was a marked increase in faecal volume and sodium output. In those patients with an ileal resection, the faecal volume and sodium output were more than two and a half times greater than those for the non-resected group. At six months there was no change in either the volume or chemistry of the effluent. After intravenous saline, no faecal response was observed. It is therefore concluded that ileostomy adaptation does occur and it is a response of the intestine to conserve body salt. This response is lacking in ileostomists who have had an ileal resection.

  1. Glutathione Levels in Human Tumors

    PubMed Central

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

    2013-01-01

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

  2. MicroRNAs Expression in the Ileal Pouch of Patients with Ulcerative Colitis Is Robustly Up-Regulated and Correlates with Disease Phenotypes

    PubMed Central

    Sherman Horev, Hadas; Elad, Hofit; Baram, Liran; Issakov, Ofer; Tulchinsky, Hagit; Pasmanik-Chor, Metsada; Shomron, Noam; Dotan, Iris

    2016-01-01

    Background Gene expression alterations are associated with disease behavior in inflammatory bowel disease (IBD). microRNAs (miRNAs) are dominant in the regulation of gene expression, and may affect IBD phenotype. Our aim was to assess mucosal miRNA expression in IBD and the correlation with intestinal inflammation. Methods We performed a large-scale analysis of ileal mucosal miRNA. Biopsies were retrieved from patients with ileal Crohn’s disease (CD), unoperated ulcerative colitis (UC) patients, UC patients after pouch surgery, and normal controls (NC). Pouch UC patients were classified as having a normal pouch (NP), chronic pouchitis (CP), and Crohn’s-like disease of the pouch (CLDP). miRNA expression was analyzed by parallel massive (next-generation) sequencing (NGS). Bioinformatics tools were applied for clustering and the detection of potential targets. Results Sixty-one subjects were recruited. The ileum of unoperated UC patients was comparable with NC. There were significant miRNA expression alterations (fold change ≥2, corrected P ≤.05) in NP (n = 6), CP (n = 40) and CLDP (n = 139), but only two expression alterations were noted in CD. More than 90% of the altered miRNAs were up-regulated, and many were predicted to be associated with significantly decreased transcripts. miRNAs alterations were generally clustered with disease phenotypes. Conclusions Ileal inflammation causes increased miRNA expression. miRNA alterations correlate with IBD phenotype, apparently by controlling the down-regulation of specific mRNAs. PMID:27536783

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

    PubMed

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

    2011-08-01

    The effects of type of grinding of barley and dehydrated alfalfa (DA) were tested in rabbits weaned at 35 d of age with an average BW of 846 ± 93 g. Four nonmedicated diets were arranged in a 2 × 2 factorial structure, with type of grinding (coarse grinding with a 4.5-mm screen or fine grinding with a 1.5-mm screen) of barley (TGB) and DA (TGDA) as the main factors. A total of 1,056 mixed-sex rabbits (264 per diet) were fattened until d 63. Most of these rabbits (216 per diet) were housed in pairs and were used only to record mortality rate. Mortality was also recorded for the remaining 192 rabbits, which were housed individually and used to determine growth performance. From this group, 100 rabbits were used to determine digestive traits. Apart from those rabbits, a different group of 88 rabbits (44 housed individually and the remaining 44 housed in pairs) was used in the digestibility trial. All rabbits in this group were used to determine ileal digestibility (13 pools of ileal digesta per diet) and ileal mucin concentration (6 pools of ileal digesta per diet), whereas only the 44 individually housed rabbits were used to assess the fecal digestibility coefficients (11 rabbits per diet). Last, a jejunal sample was excised from 32 of the 44 individually housed rabbits to determine mucosal histology. Treatments did not affect ADG, ADFI, or G:F in the entire fattening period, but in the 49- to 63-d period, the diet containing both finely ground barley and DA reduced ADFI (P=0.08) compared with the other treatments (130 vs. 137 g). Moreover, this diet increased total digestive tract (4.76%, P=0.08) and cecal content (11.3%, P=0.08) weights compared with the other 3 treatments. Pylorus (P=0.09) and mixed digesta (P=0.06) pH, respectively, were reduced from 1.53 and 1.59 to 1.37 and 1.44 when both barley and DA were finely instead of coarsely ground. Grinding both barley and DA coarsely reduced the ileal digestibility of starch (0.899 vs. 0.936, P=0.06), increased (P

  4. Organizing a mucosal defense.

    PubMed

    Newberry, Rodney D; Lorenz, Robin G

    2005-08-01

    Gastrointestinal associated lymphoid tissue can be divided into loosely organized effector sites, which include the lamina propria and intraepithelial lymphocytes, and more organized structures, such as mesenteric lymph nodes (LNs), Peyer's patches (PPs), isolated lymphoid follicles, and cryptopatches (CPs). These organized structures in the gastrointestinal tract have been hypothesized to play the role of primary lymphoid organ, supporting the extrathymic development of T lymphocytes (CPs), secondary lymphoid organs involved in the induction of the mucosal immune response (PPs), and tertiary lymphoid structures whose function is still under debate (isolated lymphoid follicles). The most widely studied lymphoid structure found in the small intestine is the PP. PPs are secondary lymphoid structures, and their development and function have been extensively investigated. However, single lymphoid aggregates resembling PPs have been also described in humans and in the murine small intestines. These isolated lymphoid follicles have both germinal centers and an overlying follicle-associated epithelium, suggesting that they also can function as inductive sites for the mucosal immune response. This review compares and contrasts the development and function of the four main organized gastrointestinal lymphoid tissues: CPs, isolated lymphoid follicles, PPs, and mesenteric LNs.

  5. Glutathione conjugation and contaminant transformation

    USGS Publications Warehouse

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

    1996-01-01

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

  6. Plant glutathione transferases

    PubMed Central

    Dixon, David P; Lapthorn, Adrian; Edwards, Robert

    2002-01-01

    The soluble glutathione transferases (GSTs, EC 2.5.1.18) are encoded by a large and diverse gene family in plants, which can be divided on the basis of sequence identity into the phi, tau, theta, zeta and lambda classes. The theta and zeta GSTs have counterparts in animals but the other classes are plant-specific and form the focus of this article. The genome of Arabidopsis thaliana contains 48 GST genes, with the tau and phi classes being the most numerous. The GST proteins have evolved by gene duplication to perform a range of functional roles using the tripeptide glutathione (GSH) as a cosubstrate or coenzyme. GSTs are predominantly expressed in the cytosol, where their GSH-dependent catalytic functions include the conjugation and resulting detoxification of herbicides, the reduction of organic hydroperoxides formed during oxidative stress and the isomerization of maleylacetoacetate to fumarylacetoacetate, a key step in the catabolism of tyrosine. GSTs also have non-catalytic roles, binding flavonoid natural products in the cytosol prior to their deposition in the vacuole. Recent studies have also implicated GSTs as components of ultraviolet-inducible cell signaling pathways and as potential regulators of apoptosis. Although sequence diversification has produced GSTs with multiple functions, the structure of these proteins has been highly conserved. The GSTs thus represent an excellent example of how protein families can diversify to fulfill multiple functions while conserving form and structure. PMID:11897031

  7. Mucosal biofilms of Candida albicans.

    PubMed

    Ganguly, Shantanu; Mitchell, Aaron P

    2011-08-01

    Biofilms are microbial communities that form on surfaces and are embedded in an extracellular matrix. C. albicans forms pathogenic mucosal biofilms that are evoked by changes in host immunity or mucosal ecology. Mucosal surfaces are inhabited by many microbial species; hence these biofilms are polymicrobial. Several recent studies have applied paradigms of biofilm analysis to study mucosal C. albicans infections. These studies reveal that the Bcr1 transcription factor is a master regulator of C. albicans biofilm formation under diverse conditions, though the most relevant Bcr1 target genes can vary with the biofilm niche. An important determinant of mucosal biofilm formation is the interaction with host defenses. Finally, studies of interactions between bacterial species and C. albicans provide insight into the communication mechanisms that endow polymicrobial biofilms with unique properties.

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

    PubMed Central

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

    1997-01-01

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

 Keywords: intestinal villous atrophy; ileum; secretory diarrhoea; bile acid malabsorption; microscopic colitis PMID:9391260

  9. [Orthotopic ileal neobladder: urodynamic and metabolic aspects. Our experience].

    PubMed

    Mangiarotti, B; Ceresoli, A; Del Nero, A; Parravicini, M; Prati, G; Currò, A; Zanetti, G P; Trinchieri, A; Pisani, E

    1996-12-01

    We subjected to a functional and metabolic evaluation (urodynamic examination + cystography) 10 patients underwent to radical cystectomy with a ileal orthotopic reservoir (VIP) for bladder cancer. At the moment patients have a minimum 3-years follow-up and they are out of disease. The medium capacity of the reservoir is about 447 ml, with a low pressure flow, a medium pressure of ureteral closing of 62.5 cm of H2O. At the cystography neither ureteral reflux nor post miction residuum have been proved. All the patients are continent, with the exception of one patient suffering from episodes of nocturnal enuresis. The metabolic evaluation hasn't proved substantial changes except the presence of hypocitraturia in the only patient in metabolic acidosis. In conclusion the ileal orthotopic reservoir showed a good long-term functionality without considerable complication of metabolism.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Ileal bladder substitute: antireflux nipple or afferent tubular segment?

    PubMed

    Studer, U E; Spiegel, T; Casanova, G A; Springer, J; Gerber, E; Ackermann, D K; Gurtner, F; Zingg, E J

    1991-01-01

    Spheroidal bladder substitutes made from double-folded ileal segments, similar to Goodwin's cup-patch technique, are devoid of major coordinated wall contractions. This, together with the reservoir's direct anastomosis to the membranous urethra, prevents major intraluminal pressure peaks and assures a residue-free voiding of sterile urine. In order to determine whether, under these conditions, an afferent tubular isoperistaltic ileal segment of 20-cm length protects the upper urinary tract as efficiently as an antireflux nipple, 60 male patients who were subjected to radical cystectomy were prospectively randomised to groups in which a bladder substitute was formed together with either of these 2 antireflux devices. An analysis of the results obtained in 20 patients from each group who could be followed for more than 1 year (median observation time 30 and 36 months) showed no differences between the groups in metabolic disturbances, kidney size, reservoir capacity, diurnal and nocturnal urinary continence, the incidence of urinary tract infection or episodes of acute pyelonephritis. Later than 1 year postoperatively, intravenous urograms of the renoureteral units of 25% of the patients with antireflux nipples showed persistent but generally slight dilatation of the upper urinary tracts. This observation was significantly more frequent than it was in patients with afferent tubular segments. Urodynamic and radiographic studies showed that the competence of the antireflux nipples was secured by the raised surrounding intravesical pressure. This, however, also resulted in a transient functional obstruction, and a gradual rise of the basal pressure in the upper urinary tracts was recorded. In patients with afferent ileal tubular segments, contrast medium could be forced upwards into the renal pelvis when the bladder substitutes were overfilled. However, despite raised intravesical pressures, peristalsis in the isoperistaltic afferent tubular segment gradually returned

  15. Common Inflammatory Disorders and Neoplasia of the Ileal Pouch: A Review of Histopathology

    PubMed Central

    Gonzalo, David Hernandez; Collinsworth, Amy L.; Liu, Xiuli

    2016-01-01

    Ileal pouch-anal anastomosis (IPAA) is the standard restorative procedure after proctocolectomy in patients with ulcerative colitis (UC) who require colectomy. The ileal pouch is susceptible to a variety of insults including mechanical injury, ischemia, fecal stasis, and infectious agents. In addition, the development of recurrent and idiopathic inflammatory bowel disease and neoplasia may occur in the ileal pouch. Although clinical, endoscopic, and radiographic examination can diagnose many ileal pouch diseases, histologic examination plays an essential role in diagnosis and management, particularly in cases with antibiotic refractory chronic pouchitis and pouch neoplasia. PMID:27785322

  16. 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 < 0.05 was considered significant. In 5-FU-injected rats, only EO administration significantly increased VH in the ileum (day 8), jejunum and jejunum-ileum junction (days 8 and 9) compared to 5-FU controls (P < 0.05). GC count was significantly reduced by 5-FU (jejunum: days 8 and 9; ileum: day 8; P < 0.05) and EO increased 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 < 0.05). Both EO and OO significantly reduced jejunal MPO on days 8 and 9; however, only EO decreased 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.

  17. Flow cytometric analysis of gut mucosal lymphocytes supports an impaired Th1 cytokine profile in spondyloarthropathy

    PubMed Central

    Van Damme, N; De Vos, M; Baeten, D; Demetter, P; Mielants, H; Verbruggen, G; Cuvelier, C; Veys, E; De Keyser, F

    2001-01-01

    OBJECTIVE—To quantify the fraction of gut mucosal lymphocytes expressing the T helper type 1 (Th1) cytokines, interferon γ (IFNγ) and interleukin (IL)2, and the Th2 cytokines, IL4 and IL10, at the single cell level in patients with spondyloarthropathy (SpA) in comparison with healthy controls.
METHODS—An improved extraction protocol was used for the enrichment of intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) from colonic and ileal biopsy specimens obtained from patients with SpA (n=20) and healthy controls (n=13). After stimulation with phorbol ester/ionomycin, expression of the intracellular cytokines IFNγ, IL2, IL4, and IL10 was determined in CD3+, CD3+CD8+ and CD3+CD8− T cells by flow cytometry.
RESULTS—In colonic LPLs, a significant decrease in IFNγ-producing CD3+ cells was observed (p=0.02) in patients with SpA. In the CD3+CD8− subset, the proportion of cells producing IFNγ and IL2 was decreased in patients with SpA (p=0.021 and p=0.027 respectively). In ileal LPLs, the percentage of IL10-producing CD3+CD8− cells was significantly increased (p=0.046).
CONCLUSION—An impaired Th1 cytokine profile is observed in gut mucosal lymphocytes from patients with SpA. This adds to the existing evidence that the gut mucosal immune apparatus is involved in the pathogenesis of SpA.

 PMID:11302872

  18. Gastroduodenal Mucosal Defense Mechanisms

    PubMed Central

    Said, Hyder; Kaji, Izumi; Kaunitz, Jonathan D.

    2015-01-01

    Purpose of Review To highlight recent developments in the field of gastroduodenal mucosal defense with emphasis on lumen-gut interactions. Recent Findings There has been a growing interest in the physiological functions of luminal chemosensors present from tongue to colon that detect organic molecules in the luminal content associated with nutrient ingestion, usually associated with specialized cells, in particular the enteroendocrine cells. These receptors transduce the release of peptide hormones, in particular proglucagon-derived products such as the glucagon-like-peptides (GLPs), which have profound effects on gut function and on metabolism. Luminal chemosensors transduce GLP release in response to changes in the cellular environment, as part of the mechanism of nutrient chemosensing. GLP-2 has important trophic effects on the intestinal mucosa, including increasing the proliferation rate of stem cells and reducing transmucosal permeability to ions and small molecules, in addition to increasing the rate of duodenal bicarbonate secretion. GLP-1, although traditionally considered an incretin that enhances the effect of insulin on peripheral tissues, also has trophic effects on the intestinal epithelium. Summary A better understanding of the mechanisms that mediate GLP release can further illuminate the importance of nutrient chemosensing as an important component of the mechanism that mediates the trophic effects of luminal nutrients. GLP-1 and -2 are already in clinical use for the treatment of diabetes and intestinal failure. Improved understanding of the control of their release and their end-organ effects will identify new clinical indications and interventions that enhance their release. PMID:26376476

  19. Dimethyl Fumarate Induces Glutathione Recycling by Upregulation of Glutathione Reductase

    PubMed Central

    Hoffmann, Christina; Dietrich, Michael; Herrmann, Ann-Kathrin; Schacht, Teresa

    2017-01-01

    Neuronal degeneration in multiple sclerosis has been linked to oxidative stress. Dimethyl fumarate (DMF) is an effective oral therapeutic option shown to reduce disease activity and progression in patients with relapsing-remitting multiple sclerosis. DMF activates the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) leading to increased synthesis of the major cellular antioxidant glutathione (GSH) and prominent neuroprotection in vitro. We previously demonstrated that DMF is capable of raising GSH levels even when glutathione synthesis is inhibited, suggesting enhanced GSH recycling. Here, we found that DMF indeed induces glutathione reductase (GSR), a homodimeric flavoprotein that catalyzes GSSG reduction to GSH by using NADPH as a reducing cofactor. Knockdown of GSR using a pool of E. coli RNase III-digested siRNAs or pharmacological inhibition of GSR, however, also induced the antioxidant response rendering it impossible to verify the suspected attenuation of DMF-mediated neuroprotection. However, in cystine-free medium, where GSH synthesis is abolished, pharmacological inhibition of GSR drastically reduced the effect of DMF on glutathione recycling. We conclude that DMF increases glutathione recycling through induction of glutathione reductase. PMID:28116039

  20. 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.

  1. 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.

  2. Microscopic and functional anatomy of the ileal papilla and caecocolonic valve in the rat.

    PubMed

    Roger, T; Cabanie, P; Ferre, J P

    1991-01-01

    In the rat, topographic and X-ray studies of the caecum and ascending colon, together with microscopic anatomic observations of the ileal papilla and caecocolonic valve, showed that junction structures contribute to prevent the backflow of the caecal content into the ileum and to direct the ileal content within the caecum whatever the various positions of the caecum in the abdominal cavity.

  3. 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

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

    PubMed

    Nýdlová, Erika; Vrbová, Martina; Cesla, Petr; Jankovičová, Barbora; Ventura, Karel; Roušar, Tomáš

    2014-09-01

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

  5. Alteration of the Redox State with Reactive Oxygen Species for 5-Fluorouracil-Induced Oral Mucositis in Hamsters

    PubMed Central

    Wada-Takahashi, Satoko; Takahashi, Shun-suke; Lee, Masaichi Chang-il

    2013-01-01

    Oral mucositis is often induced in patients receiving cancer chemotherapy treatment. It has been reported that oral mucositis can reduce quality of life, as well as increasing the incidence of mortality. The participation of reactive oxygen species (ROS) in the pathogenesis of oral mucositis is well known, but no report has actually demonstrated the presence of ROS. Thus, the purpose of this study was thus to demonstrate the involvement of ROS and the alteration of the redox state in oral mucositis using an in vivo L-band electron spin resonance (ESR) technique. An oral mucositis animal model induced by treatment of 5-fluorouracil with 10% acetic acid in hamster cheek pouch was used. Lipid peroxidation was measured as the level of malondialdehyde determined by the thiobarbituric acid reaction. The rate constants of the signal decay of nitroxyl compounds using in vivo L-band ESR were calculated from the signal decay curves. Firstly, we established the oral mucositis animal model induced by treatment of 5-fluorouracil with acetic acid in hamster cheek pouch. An increased level of lipid peroxidation in oral mucositis was found by measuring malondialdehyde using isolated hamster cheek pouch ulcer. In addition, as a result of in vivo L-band ESR measurements using our model animals, the decay rate constants of carbamoyl-PROXYL, which is a reagent for detecting the redox balance in tissue, were decreased. These results suggest that a redox imbalance might occur by excessive generation of ROS at an early stage of oral mucositis and the consumption of large quantities of antioxidants including glutathione in the locality of oral mucositis. These findings support the presence of ROS involved in the pathogenesis of oral mucositis with anti-cancer therapy, and is useful for the development of novel therapies drugs for oral mucositis. PMID:24376587

  6. Protective effect of Matricaria chamomilla on ethanol-induced acute gastric mucosal injury in rats.

    PubMed

    Cemek, Mustafa; Yilmaz, Ezgi; Büyükokuroğlu, Mehmet Emin

    2010-07-01

    The antiulcerogenic and antioxidant properties of Matricaria chamomilla L. (Compositae) hydroalcoholic extract (MCE) on ethanol-induced gastric mucosal injury were investigated in rats. After the induction of gastric mucosal injury, all groups were sacrificed; the gastric ulcer index was calculated, and malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood and gastric tissue, and serum ascorbic acid, retinol, and beta-carotene levels were measured in all groups. Pretreatment with MCE at some doses significantly reduced gastric lesions. Again, some doses of MCE significantly reduced the MDA, and significantly increased GSH levels in gastric tissue or whole blood. Serum beta-carotene and retinol levels were significantly higher in the 200 mg/kg MCE-administered group with respect to control. As a result, MCE clearly has a protective effect against ethanol-induced gastric mucosal lesions, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in antioxidant activity.

  7. Biology of HIV Mucosal Transmission

    PubMed Central

    Wu, Li

    2008-01-01

    Purpose of review HIV-1 mucosal transmission plays a critical role in HIV-1 infection and AIDS pathogenesis. This review summarizes the latest advances in biological studies of HIV-1 mucosal transmission, highlighting the implications of these studies in the development of microbicides to prevent HIV-1 transmission. Recent findings New studies of initial HIV-1 infection using improved culture models updated the current view of mucosal transmission. Mechanistic studies enhanced our understanding of cell-cell transmission of HIV-1 mediated by the major target cells, including dendritic cells, CD4+ T cells, and macrophages. Increasing evidence indicated the significance of host factors and immune responses in HIV-1 mucosal infection and transmission. Summary Recent progress in HIV-1 mucosal infection and transmission enriches our knowledge of virus-host interactions and viral pathogenesis. Functional studies of HIV-1 interactions with host cells can provide new insights into the design of more effective approaches to combat HIV-1 infection and AIDS. PMID:18802490

  8. A plausible explanation for male dominance in typhoid ileal perforation.

    PubMed

    Khan, Mohammad

    2012-01-01

    The phenomenon of consistent male dominance in typhoid ileal perforation (TIP) is not well understood. It cannot be explained on the basis of microbial virulence, Peyer's patch anatomy, ileal wall thickness, gastric acidity, host genetic factors, or sex-linked bias in hospital attendance. The cytokine response to an intestinal infection in males is predominantly proinflammatory as compared with that in females, presumably due to differences in the sex hormonal milieu. Sex hormone receptors have been detected on lymphocytes and macrophages, including on Peyer's patches, inflammation of which (probably similar to the Shwartzman reaction/Koch phenomenon) is the forerunner of TIP, and is not excluded from the regulatory effects of sex hormones. Hormonal control of host-pathogen interaction may override genetic control. Environmental exposure to Salmonella typhi may be more frequent in males, presumably due to sex-linked differences in hygiene practices and dining-out behavior. A plausible explanation of male dominance in TIP could include sex-linked differences in the degree of natural exposure of Peyer's patches to S. typhi. An alternative explanation may include sexual dimorphism in host inflammatory response patterns in Peyer's patches that have been induced by S. typhi. Both hypotheses are testable.

  9. Parastomal hernias after radical cystectomy and ileal conduit diversion

    PubMed Central

    Donahue, Timothy F.

    2016-01-01

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

  10. Chemotherapy-induced mucositis is associated with changes in proteolytic pathways.

    PubMed

    Leblond, Jonathan; Le Pessot, Florence; Hubert-Buron, Aurélie; Duclos, Célia; Vuichoud, Jacques; Faure, Magali; Breuillé, Denis; Déchelotte, Pierre; Coëffier, Moïse

    2008-02-01

    Mucositis, a common toxic side effect of chemotherapy, is characterized by an arrest of cell proliferation and a loss of gut barrier function, which may cause treatment reduction or withdrawal. Gut integrity depends on nutritional and metabolic factors, including the balance between protein synthesis and proteolysis. The effects of methotrexate (MTX; a frequently used chemotherapeutic agent) on intestinal proteolysis and gut barrier function were investigated in rats. Male Sprague-Dawley rats received 2.5 mg/kg of MTX subcutaneously during 3 days and were euthanized at Day 4 (D4) or Day 7 (D7). We observed at D4 that MTX induced mucosal damage and increased intestinal permeability (7-fold) and the mucosal concentration of interleukin (IL)-1beta and IL-6 (4- to 6-fold). In addition, villus height and glutathione content significantly decreased. Intestinal proteolysis was also affected by MTX as cathepsin D activity increased at D4, whereas chymotrypsin-like proteasome activity decreased and calpain activities remained unaffected. At D7, cathepsin D activity was restored to control levels, but proteasome activity remained reduced. This disruption of proteolysis pathways strongly contributed to mucositis and requires further study. Lysosomal proteolytic activity may be considered the main proteolytic pathway responsible for alteration of mucosal integrity and intestinal permeability during mucositis, as cathepsin D activity was found to be correlated with mucosal atrophy and intestinal permeability. Proteasome regulation could possibly be an adaptive process for survival. Future investigation is warranted to target proteolytic pathways with protective nutritional or pharmacological therapies during mucositis.

  11. 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.

  12. Comparison of postoperative acute kidney injury between ileal conduit and neobladder urinary diversions after radical cystectomy

    PubMed Central

    Joung, Kyoung-Woon; Kong, Yu-Gyeong; Yoon, Syn-Hae; Kim, Yeon Ju; Hwang, Jai-Hyun; Hong, Bumsik; Kim, Young-Kug

    2016-01-01

    Abstract Ileal conduit and neobladder urinary diversions are frequently performed after radical cystectomy. However, complications after radical cystectomy may be different according to the type of urinary diversion. Acute kidney injury (AKI) is a common complication after surgery and increases costs, morbidity, and mortality of hospitalized patients. This study was performed to compare the incidence of postoperative AKI between ileal conduit and neobladder urinary diversions after radical cystectomy. All consecutive patients who underwent radical cystectomy in 2004 to 2014 in a single tertiary care center were identified. The patients were divided into the ileal conduit and ileal neobladder groups. Preoperative variables, including demographics, cancer-related data and laboratory values, as well as intraoperative data and postoperative outcomes, including AKI, intensive care unit admission rate, and the duration of hospital stay, were evaluated between the groups. Postoperative AKI was defined according to the Kidney Disease: Improving Global Outcome criteria. Propensity score matching analysis was performed to reduce the influence of possible confounding variables and adjust for intergroup differences. After performing 1:1 propensity score matching, the ileal conduit and ileal neobladder groups each included 101 patients. The overall incidence of AKI after radical cystectomy was 30.7% (62 out of 202) and the incidences did not significantly differ between the groups (27 [26.7%], ileal conduit group vs 35 [34.7%], ileal neobladder group, P = 0.268). Intraoperative data, intensive care unit admission rate, and the duration of hospital stay were not significantly different between the groups. Postoperative AKI did not significantly differ between ileal conduit and neobladder urinary diversions after radical cystectomy. This finding provides additional information useful for appropriate selection of the urinary diversion type in conjunction with radical cystectomy

  13. The importance and regulation of hepatic glutathione.

    PubMed Central

    Kaplowitz, N.

    1981-01-01

    Glutathione plays a key role in the liver in detoxification reactions and in regulating the thiol-disulfide status of the cell. Glutathione synthesis is regulated mainly by the availability of precursor cysteine and the concentration of glutathione itself which feeds back to regulate its own synthesis. Degradation of hepatic glutathione is principally regulated by the efflux of reduced and oxidized glutathione into both sinusoidal plasma and bile. In addition, glutathione may be consumed in conjugation reactions. Under conditions of oxidative stress, the liver exports oxidized glutathione into bile in a concentrative fashion, whereas under basal conditions, mainly reduced glutathione is exported into bile and blood. The mechanism of export of reduced glutathione into bile and sinusoidal blood is poorly understood. PMID:7342494

  14. Glutathione metabolism and Parkinson's disease.

    PubMed

    Smeyne, Michelle; Smeyne, Richard Jay

    2013-09-01

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

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

    PubMed

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

    2015-03-21

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

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

    PubMed Central

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

    1993-01-01

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

  17. Dietary grape seed proanthocyanidins (GSPs) improve weaned intestinal microbiota and mucosal barrier using a piglet model

    PubMed Central

    Han, Meng; Song, Peixia; Huang, Chang; Rezaei, Arash; Farrar, Shabnam; Brown, Michael A.; Ma, Xi

    2016-01-01

    Proanthocyanidins have been suggested as an effective antibiotic alternative, however their mechanisms are still unknown. The present study investigated the effects of grape seed proanthocyanidins on gut microbiota and mucosal barrier using a weaned piglet model in comparison with colistin. Piglets weaned at 28 day were randomly assigned to four groups treated with a control ration, or supplemented with 250 mg/kg proanthocyanidins, kitasamycin/colistin, or 250 mg/kg proanthocyanidins and half-dose antibiotics, respectively. On day 28, the gut chyme and tissue samples were collected to test intestinal microbiota and barrier function, respectively. Proanthocyanidins treated piglets had better growth performance and reduced diarrhea incidence (P < 0.05), accompanied with decreased intestinal permeability and improved mucosal morphology. Gene sequencing analysis of 16S rRNA revealed that dietary proanthocyanidins improved the microbial diversity in ileal and colonic digesta, and the most abundant OTUs belong to Firmicutes and Bacteroidetes spp. Proanthocyanidins treatment decreased the abundance of Lactobacillaceae, and increased the abundance of Clostridiaceae in both ileal and colonic lumen, which suggests that proanthocyanidins treatment changed the bacterial composition and distribution. Administration of proanthocyanidins increased the concentration of propionic acid and butyric acid in the ileum and colon, which may activate the expression of GPR41. In addition, dietary proanthocyanidins improved the antioxidant indices in serum and intestinal mucosa, accompanied with increasing expression of barrier occludin. Our findings indicated that proanthocyanidins with half-dose colistin was equivalent to the antibiotic treatment and assisted weaned animals in resisting intestinal oxidative stress by increasing diversity and improving balance of gut microbes. PMID:27880936

  18. Increased Expression of DUOX2 is an Epithelial Response to Mucosal Dysbiosis Required for Immune Homeostasis in Mouse Intestine

    PubMed Central

    Grasberger, Helmut; Gao, Jun; Nagao-Kitamoto, Hiroko; Kitamoto, Sho; Zhang, Min; Kamada, Nobuhiko; Eaton, Kathryn A.; El-Zaatari, Mohamad; Shreiner, Andrew B.; Merchant, Juanita L.; Owyang, Chung; Kao, John Y.

    2015-01-01

    BACKGROUND & AIMS Dual oxidase 2 (DUOX2), a hydrogen-peroxide generator at the apical membrane of gastrointestinal epithelia, is upregulated in patients with inflammatory bowel disease (IBD) before the onset of inflammation, but little is known about its effects. We investigated the role of DUOX2 in maintaining mucosal immune homeostasis in mice. METHODS We analyzed the regulation of DUOX2 in intestinal tissues of germ-free vs conventional mice, mice given antibiotics or colonized with only segmented filamentous bacteria, mice associated with human microbiota, and mice with deficiencies in interleukin (IL)23 and 22 signaling. We performed 16S rRNA gene quantitative PCR of intestinal mucosa and mesenteric lymph nodes of Duoxa−/− mice that lack functional DUOX enzymes. Genes differentially expressed in Duoxa−/− mice compared to co-housed wild type littermates were correlated with gene expression changes in early-stage IBD using gene set enrichment analysis. RESULTS Colonization of mice with segmented filamentous bacteria upregulated intestinal expression of DUOX2. DUOX2 regulated redox-signaling within mucosa-associated microbes and restricted bacterial access to lymphatic tissues of the mice, thereby reducing microbiota-induced immune responses. Induction of Duox2 transcription by microbial colonization did not require the mucosal cytokines IL17 or IL22, although IL22 increased expression of Duox2. Dysbiotic, but not healthy human microbiota, activated a DUOX2 response in recipient germ-free mice that corresponded to abnormal colonization of the mucosa with distinct populations of microbes. In Duoxa−/− mice, abnormalities in ileal mucosal gene expression at homeostasis recapitulated those in patients with mucosal dysbiosis. CONCLUSIONS DUOX2 regulates interactions between the intestinal microbiota and the mucosa to maintain immune homeostasis in mice. Mucosal dysbiosis leads to increased expression of DUOX2, which might be a marker of perturbed mucosal

  19. 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

  20. 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

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

    PubMed

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

    2015-01-01

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

  2. Ileo-ileal knot: a rare case of acute strangulated intestinal obstruction

    PubMed Central

    Taniguchi, Kohei; Iida, Ryo; Watanabe, Tomohiko; Nitta, Masahiko; Tomioka, Masao; Uchiyama, Kazuhisa; Takasu, Akira

    2017-01-01

    ABSTRACT Strangulated intestinal obstruction is one of the most common types of acute abdomen and requires urgent surgical treatment. Herein, we report a very rare case of strangulated intestinal obstruction caused by an ileo-ileal knot. An 80-year-old woman was admitted to our hospital with suspicion of strangulation ileus and underwent emergency laparotomy after investigation by exploratory single-port laparoscopy. During surgery, a small bowel gangrene caused by an ileo-ileal knot was found. The gangrenous segment was resected, and primary anastomosis was performed. Post-operative recovery was uneventful except for a minor wound infection. Our extensive search of the literature found only 7 case reports of ileo-ileal knot including ours. An ileo-ileal knot should be considered in the differential diagnosis of acute intestinal obstruction, because this rare phenomenon requires urgent surgical treatment; and some complications should be considered during or after surgery. PMID:28303069

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

    PubMed Central

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

    2013-01-01

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

  4. Genetics Home Reference: glutathione synthetase deficiency

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions glutathione synthetase deficiency glutathione synthetase ...

  5. Acute necrotizing enterocolitis of preterm piglets is characterized by dysbiosis of ileal mucosa-associated bacteria

    PubMed Central

    Azcarate-Peril, M Andrea; Foster, Derek M; Cadenas, Maria B; Stone, Maria R; Jacobi, Sheila K; Stauffer, Stephen H; Pease, Anthony

    2011-01-01

    Investigation of bacteria involved in pathogenesis of necrotizing enterocolitis (NEC) is limited by infant fragility, analysis restricted to feces, use of culture-based methods and lack of clinically-relevant animal models. This study used a unique preterm piglet model to characterize spontaneous differences in microbiome composition of NEC-predisposed regions of gut. Preterm piglets (n = 23) were cesarean-delivered and nurtured for 30 h over which time 52% developed NEC. Bacterial DNA from ileal content, ileal mucosa and colonic mucosa were PCR amplified, subjected to terminal restriction fragment length polymorphism (TRFLP) analysis and targeted 16s rDNA qPCR. Preterm ileal mucosa was specifically bereft in diversity of bacteria compared to ileal content and colonic mucosa. Preterm ileum was restricted to representation by only Proteobacteria, Firmicutes, Cyanobacteria and Chloroflexi. In piglets with NEC, ileal mucosa was uniquely characterized by increases in number of Firmicutes and diversity of phyla to include Actinobacteria and uncultured bacteria. Five specific TRFLP profiles, corresponding in closest identity to Clostridium butyricum, C. neonatale, C. proteolyticum, Streptomyces spp. and Leptolyngbya spp., were significantly more prevalent or observed only among samples from piglets with NEC. Total numbers of Clostridium spp. and C. butyricum were significantly greater in samples of NEC ileal mucosa but not ileal content or colonic mucosa. These results provide strong support for ileal mucosa as a focus for investigation of specific dysbiosis associated with NEC and suggest a significant role for Clostridium spp., and members of the Actinobacteria and Cyanobacteria in the pathogenesis of NEC in preterm piglets. PMID:21983069

  6. [Orthotopic ileal neobladder: technical procedures and long-term follow-up].

    PubMed

    Leidi, G L; Berti, G L; Giola, V; Longoni, E; Paccaduscio, A; Raimoldi, A; Bacchioni, A M

    1999-06-01

    From January 1992 to September 1997, 29 male patients between the age of 39 and 71 affected by localized bladder cancer underwent radical cystectomy and received detubularized orthotopic ileal neobladder. In most cases we performed the ileal neobladder utilizing the Studer technique, preferring the Wallace 1 method for the uretero-ileal anastomosis, that seems to reduce the risk of stenosis. In some patients we experimented different techniques. One of these was the utilization of staplers but, at present, we are no longer using this procedure due to its high costs without any real advantage in operative time. Another technique is the performance of continuous suture in catgut 000 on the ileal aperture edges for the anastomosis with the urethra, because we believe that this method makes the ileal wall stronger. Usually we apply 6 stitches in vicryl 000 for the urethro-ileal anastomosis. In 14-28 days, after a cystography to exclude the presence of urinary fistula, the catheter was removed. 6 months later an evaluation was made utilizing an auto-evaluation questionnaire, biochemical, radiological and urodynamic examinations. The diurnal continence (96%), the nocturnal continence (71%), the renal function preservation (normal in 86% of patients), the radiological, biochemical and urodynamic (low pressure and high capacity of the neobladder) results were comparable with those published in literature. The discrete percentage of urinary refluxes observed (39%) puts in doubt the real efficacy of the undetubularized ileal tract as an antireflux mechanism, however it does not seem to determine an important reduction of renal function, as confirmed in the check up five years later. In our experience, this operation reduces the risk of stenosis of the uretero-ileal anastomosis.

  7. Sublingual glyceryl trinitrate during colonoscopy and terminal ileal intubation: a randomized controlled trial.

    PubMed

    Hill, Patsy-Anne; Panteleimonitis, Sofoklis; McKay, Graham; Watson, Carol; Prach, Andre; Macdonald, Angus

    2017-02-01

    Background and aims Sublingual glyceryl trinitrate has been used as an aid to cannulate the Sphincter of Oddi during endoscopic retrograde cholangiopancreatography. Its role in terminal ileal intubation during colonoscopy is unknown. This study examines the role of sublingual glyceryl trinitrate in terminal ileal intubation during colonoscopy. Methods A triple-blind randomized controlled trial comparing sublingual glyceryl trinitrate (800 µg) vs. placebo (saline) in relation to terminal ileal intubation during colonoscopy was performed. Following caecal intubation, participants received sublingual glyceryl trinitrate/placebo followed by a 2-min observation period before intubation was attempted. Data on time to intubate the terminal ileum and intubation rate were collected. Results A total of 110 patients (age: 58 years (18-75)) were recruited and randomised as per protocol: 54 received sublingual glyceryl trinitrate. Terminal ileal intubation was successful in all patients receiving sublingual glyceryl trinitrate and in 53 (94.6%) of those receiving saline ( p = 0.243: Fischer's exact). The median time taken for ileal intubation after application of spray was 72.5 (7-900) s in the glyceryl trinitrate group compared with 125 (5-900) s in the placebo group ( p = 0.150: Mann-Whitney). There were no major adverse events reported in either group. Conclusions Terminal ileal intubation rates and timing were very good in both groups. Routine sublingual glyceryl trinitrate was not proven to be beneficial in improving terminal ileal intubation or intubation success rates in the hands of experienced colonoscopists. However, trends in this small study might suggest that glyceryl trinitrate could be useful in the hands of less experienced colonoscopists or in difficult terminal ileal intubation cases.

  8. Repeat ileal pouch-anal anastomosis to salvage septic complications of pelvic pouches: clinical outcome and quality of life assessment.

    PubMed Central

    Fazio, V W; Wu, J S; Lavery, I C

    1998-01-01

    OBJECTIVE: To evaluate the outcome of repeat ileal pouch-anal anastomosis (IPAA) for septic complications of pelvic pouch surgery; to assess the relationship between diagnosis and outcome; to assess quality of life after surgery. SUMMARY BACKGROUND DATA: Pelvic and perineal sepsis due to ileal pouch-anal anastomotic leaks frequently results in pouch loss. Many surgeons believe that pelvic sepsis and/or dense pelvic fibrosis makes salvage surgery unsafe or that pouches salvaged under these circumstances may not function well. As a result, there are few studies of pouch salvage procedures for septic indications. METHODS: The authors reviewed records of Cleveland Clinic Foundation patients who had undergone repeat IPAA surgery after septic complications from previous pelvic pouch surgery and who had completed at least 6 months of follow-up. Final diagnoses included ulcerative colitis (n = 22), Crohn's disease (n = 10), indeterminate colitis (n = 1), and familial polyposis (n = 2). Patients with functioning pouches were interviewed about functional problems and quality of life using an in-house questionnaire and the validated SF-36 Health Survey. RESULTS: Of 35 patients, 30 (86%) had a functioning pouch 6 months after repeat IPAA. In 4 patients, complications led to pouch removal or fecal diversion. One patient declined stoma closure. Of the patients with mucosal ulcerative colitis (MUC), 95% (21/22) had a functioning pouch 6 months after surgery. For patients with Crohn's disease (CD) 60% (6/10) have maintained a functioning pouch. Of the 30 patients with functioning pouches, 17 (57%) rated their quality of life as either "good" or "excellent," the remaining 13 (43%) selected "fair" or "poor." All said they would choose repeat IPAA surgery again. An SF-36 Health Survey completed by all patients with a functioning pouch at follow-up showed a mean physical component scale of 46.4 and a mean mental component scale of 47.6, scores well within the normal limit. CONCLUSIONS

  9. Mucosal immunology of food allergy.

    PubMed

    Berin, M Cecilia; Sampson, Hugh A

    2013-05-06

    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 immunoglobulin E (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 the microbiome, are likely to shed light on factors responsible for the growing clinical problem of food allergy.

  10. Cryopreservation of Human Mucosal Leukocytes

    PubMed Central

    Shu, Zhiquan; Levy, Claire N.; Ferre, April L.; Hartig, Heather; Fang, Cifeng; Lentz, Gretchen; Fialkow, Michael; Kirby, Anna C.; Adams Waldorf, Kristina M.; Veazey, Ronald S.; Germann, Anja; von Briesen, Hagen; McElrath, M. Juliana; Dezzutti, Charlene S.; Sinclair, Elizabeth; Baker, Chris A. R.; Shacklett, Barbara L.; Gao, Dayong; Hladik, Florian

    2016-01-01

    Background Understanding how leukocytes in the cervicovaginal and colorectal mucosae respond to pathogens, and how medical interventions affect these responses, is important for developing better tools to prevent HIV and other sexually transmitted infections. An effective cryopreservation protocol for these cells following their isolation will make studying them more feasible. Methods and Findings To find an optimal cryopreservation protocol for mucosal mononuclear leukocytes, we compared cryopreservation media and procedures using human vaginal leukocytes and confirmed our results with endocervical and colorectal leukocytes. Specifically, we measured the recovery of viable vaginal T cells and macrophages after cryopreservation with different cryopreservation media and handling procedures. We found several cryopreservation media that led to recoveries above 75%. Limiting the number and volume of washes increased the fraction of cells recovered by 10–15%, possibly due to the small cell numbers in mucosal samples. We confirmed that our cryopreservation protocol also works well for both endocervical and colorectal leukocytes. Cryopreserved leukocytes had slightly increased cytokine responses to antigenic stimulation relative to the same cells tested fresh. Additionally, we tested whether it is better to cryopreserve endocervical cells on the cytobrush or in suspension. Conclusions Leukocytes from cervicovaginal and colorectal tissues can be cryopreserved with good recovery of functional, viable cells using several different cryopreservation media. The number and volume of washes has an experimentally meaningful effect on the percentage of cells recovered. We provide a detailed, step-by-step protocol with best practices for cryopreservation of mucosal leukocytes. PMID:27232996

  11. Ileal adenocarcinoma in a mild phenotype of abetalipoproteinemia.

    PubMed

    Al-Shali, K; Wang, J; Rosen, F; Hegele, R A

    2003-02-01

    Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder that is characterized by defective assembly and secretion of plasma apolipoprotein (apo) B-containing lipoproteins. This disorder results from mutations in the MTP gene encoding the microsomal triglyceride transfer protein. We report a 58-year-old male homozygote for a missense mutation, S590I, in MTP. The patient had a lifelong history of fat malabsorption, but was only diagnosed with ABL at age 52, based upon such classic features as absence of apo B-containing lipoproteins, acanthocytosis, atypical retinitis pigmentosa and markedly depressed serum beta-carotene concentration. However, his presentation was notable not only by survival to the sixth decade of life without specific treatment, but also by the absence of neurological involvement and by normal serum vitamin E concentration. He subsequently developed adenocarcinoma of the ileum, which required ileal resection. Therefore, this missense mutation appears to be associated with a late-presenting and relatively mild ABL phenotype that lacks some classical features, particularly neuropathy, but appears to be associated with other atypical features, specifically small intestinal cancer.

  12. Action on ileal smooth muscle of synthetic detergents and pardaxin.

    PubMed

    Primor, N

    1986-01-01

    Pardaxin (PX), a toxic and repellent substance isolated from the Red Sea flatfish, causes a sharp ball-like profile of drop of saline placed on a hydrophobic film to turn into a flattened one. This effect results with a decrease of the contact angle (theta) from 96 degrees to a maximum of 42 degrees at 10(-4) M of PX. The action of sodium dodecyl sulphate (SDS), a synthetic anionic detergent, benzalkonium chloride (BAC) cationic detergent and pardaxin (PX) a toxic protein with detergent properties, were studied in the ileal guinea-pig longitudinal smooth muscle preparation. SDS (4 X 10(-4) M) and PX (5 X 10(-6) M) diminished the muscle contractile response to field stimulation (0.1 Hz, 1 msec) and to acetylcholine (Ach) and to histamine and elicited a prolonged (4-6 min) TTX-insensitive muscle contraction. The dose dependence of muscle contraction to SDS and PX was found to be sigmoidal and occurred over a narrow range of concentrations. The SDS- but not PX-induced muscle contraction could be reduced by diphenhydramine (H1 antihistamine). BAC (10(-5)-10(-4) M) suppressed the muscle's contractile response to electrical stimulation (0.1 Hz, 1 msec), to Ach, histamine and 5-hydroxytryptamine but did not produce muscle contraction. PX at concentrations higher than 5 X 10(-6) M is a potent detergent and at this concentration shares several pharmacological similarities with SDS.

  13. 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.

  14. 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 Crohn’s 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

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

    PubMed

    Erden, M; Bor, N M

    1984-04-01

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

  16. The Development of an AIDS Mucosal Vaccine

    PubMed Central

    Tang, Xian; Chen, Zhiwei

    2010-01-01

    It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1), a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies. PMID:21994611

  17. Topical therapy for mucosal yeast infections.

    PubMed

    Summers, Paul R

    2011-01-01

    Mucosal yeast infection is best understood as a consequence of compromised mucosal cell-mediated and innate immunity. Defense against oral candidiasis is dominantly cell mediated. The innate immune system may play the main role in regulating vulvovaginal yeast infection. Conditions that compromise cell-mediated immunity such as leukemia, severe illness and HIV infection must be considered as predisposing factors for recurrent oral candidiasis. Compromise of vaginal innate immunity due to mucosal allergy or due to a genetic defect such as mannose-binding lectin deficiency contributes to chronic vulvovaginal yeast infection. Treatment of cofactors must be considered in order to achieve control in recurrent mucosal yeast infection.

  18. 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 7α-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

  19. Voice Disorders in Mucosal Leishmaniasis

    PubMed Central

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

    2014-01-01

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

  20. 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.

  1. 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.

  2. 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.

  3. Differences in transcriptomic profile and IgA repertoire between jejunal and ileal Peyer's patches.

    PubMed

    Levast, Benoît; De Monte, Michèle; Melo, Sandrine; Chevaleyre, Claire; Berri, Mustapha; Salmon, Henri; Meurens, François

    2010-02-01

    In many species such as sheep and pig, there are two types of Peyer's patches (PP): several discrete patches in the jejunum and a long and continuous patch in the ileum. Most of the immunoglobulin A in the gut is generated by B-cells in the PP germinal centers. Moreover, swine like ovine ileal PP might be important for antigen independent B-cell repertoire diversification. We examined, by quantitative real-time PCR, the expression of 36 transcripts of antimicrobial peptides, chemokines, interleukines, Toll-like receptors and transcription factors from both PP and we highlighted the differences by a principal component analysis. Ileal PP was characterized by a higher mRNA expression of CCL28, IL5, IL10, TLR2 and TLR4 while jejunal PP showed higher mRNA expression of antimicrobial peptides, CCL25, FOXP3, IL4, T-Bet, TSLP and SOCS2. Then, we analyzed some VDJ rearrangements to assess immunoglobulin repertoire diversity in jejunal and ileal PP from weaned piglets. The IgA and IgM repertoires were more diverse in ileal than in jejunal piglet PP. All these results could be related to the rarefaction of interfollicular T-cell zone and the presence in ileal versus jejunal lumen of a more diversified microflora. These findings shed a light on the functional differences between both PP.

  4. 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.

  5. Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats.

    PubMed

    Arslan, Aynur; Ozcicek, Adalet; Suleyman, Bahadir; Coban, Taha Abdulkadir; Cimen, Ferda Keskin; Nalkiran, Hatice Sevim; Kuzucu, Mehmet; Altuner, Durdu; Cetin, Nihal; Suleyman, Halis

    2016-11-01

    Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. The control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. The duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide.

  6. Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats

    PubMed Central

    Arslan, Aynur; Ozcicek, Adalet; Suleyman, Bahadir; Coban, Taha Abdulkadir; Cimen, Ferda Keskin; Nalkiran, Hatice Sevim; Kuzucu, Mehmet; Altuner, Durdu; Cetin, Nihal; Suleyman, Halis

    2016-01-01

    Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. The control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. The duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide. PMID:27333839

  7. Modulation of gut mucosal biofilms.

    PubMed

    Kleessen, Brigitta; Blaut, Michael

    2005-04-01

    Non-digestible inulin-type fructans, such as oligofructose and high-molecular-weight inulin, have been shown to have the ability to alter the intestinal microbiota composition in such a way that members of the microbial community, generally considered as health-promoting, are stimulated. Bifidobacteria and lactobacilli are the most frequently targeted organisms. Less information exists on effects of inulin-type fructans on the composition, metabolism and health-related significance of bacteria at or near the mucosa surface or in the mucus layer forming mucosa-associated biofilms. Using rats inoculated with a human faecal flora as an experimental model we have found that inulin-type fructans in the diet modulated the gut microbiota by stimulation of mucosa-associated bifidobacteria as well as by partial reduction of pathogenic Salmonella enterica subsp. enterica serovar Typhimurium and thereby benefit health. In addition to changes in mucosal biofilms, inulin-type fructans also induced changes in the colonic mucosa stimulating proliferation in the crypts, increasing the release of mucins, and altering the profile of mucin components in the goblet cells and epithelial mucus layer. These results indicate that inulin-type fructans may stabilise the gut mucosal barrier. Dietary supplementation with these prebiotics could offer a new approach to supporting the barrier function of the mucosa.

  8. Antimicrobials, mucosal coating agents, anesthetics, analgesics, and nutritional supplements for alimentary tract mucositis.

    PubMed

    Barasch, Andrei; Elad, Sharon; Altman, Arnold; Damato, Kathryn; Epstein, Joel

    2006-06-01

    This review focuses on the value of several groups of agents for the prevention and treatment of mucositis. The review refers to alimentary mucositis as a generalized term that includes oral mucositis and gastrointestinal mucositis. This paper is part of the systematic review made by the mucositis study group which operates in the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO). Several new guidelines are suggested in this review as an update to the primary systematic review that was published by the same group in 2004.

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

    PubMed Central

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

    2007-01-01

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

  10. The role of glutathione in cancer.

    PubMed

    Balendiran, Ganesaratnam K; Dabur, Rajesh; Fraser, Deborah

    2004-01-01

    Glutathione is an abundant natural tripeptide found within almost all cells. Glutathione is highly reactive and is often found conjugated to other molecules via its sulfhydryl moiety. It instils several vital roles within a cell including antioxidation, maintenance of the redox state, modulation of the immune response and detoxification of xenobiotics. With respect to cancer, glutathione metabolism is able to play both protective and pathogenic roles. It is crucial in the removal and detoxification of carcinogens, and alterations in this pathway, can have a profound effect on cell survival. However, by conferring resistance to a number of chemotherapeutic drugs, elevated levels of glutathione in tumour cells are able to protect such cells in bone marrow, breast, colon, larynx and lung cancers. Here we present a number of studies investigating the role of glutathione in promoting cancer, impeding chemotherapy, and the use of glutathione modulation to enhance anti-neoplastic therapy.

  11. Localized Pemphigus Vegetans without Mucosal Involvement.

    PubMed

    Jain, Vk; Jindal, N; Imchen, S

    2014-03-01

    Pemphigus vegetans is a rare variant of pemphigus vulgaris. A 62-year-old woman presented with erythematous moist vegetative plaque on the left breast and left groin. There was no mucosal involvement. Histopathological and direct immunofluorescence findings were suggestive of pemphigus vegetans. She showed excellent response to oral steroids. Literature is scarcely available on the limited involvement with pemphigus vegetans without mucosal involvement.

  12. 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

  13. Mucosal Wave Measurement and Visualization Techniques

    PubMed Central

    Krausert, Christopher R.; Olszewski, Aleksandra E.; Taylor, Lindsay N.; McMurray, James S.; Dailey, Seth H.; Jiang, Jack J.

    2010-01-01

    Organized vibration of the vocal folds is critical to high quality voice production. When the vocal folds oscillate, the superficial tissue of the vocal fold is displaced in a wave-like fashion, creating the so called “mucosal wave”. Because the mucosal wave is dependent on vocal fold structure, physical alterations of that structure cause mucosal wave abnormalities. Visualization and quantification of mucosal wave properties have become useful parameters in diagnosing and managing vocal fold pathology. Mucosal wave measurement provides information about vocal fold characteristics that cannot be determined with other assessment techniques. Here, we discuss the benefits, disadvantages, and clinical applicability of the different mucosal wave measurement techniques, such as electroglottography (EGG), photoglottography (PGG), and ultrasound and visualization techniques that include videokymography (VKG), stroboscopy, and high-speed digital imaging (HSDI). The various techniques and their specific uses are reviewed with the intention of helping researchers and clinicians choose a method for a given situation and understand its limitations as well as its potential applications. Recent applications of these techniques for quantitative assessment demonstrate that additional research must be conducted to realize the full potential of these tools. Evaluations of existing research and recommendations for future research are given to promote both the quantitative study of the mucosal wave through accurate and standardized measurement of mucosal wave parameters and the development of reliable methods with which physicians can diagnose vocal disorders. PMID:20471798

  14. 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

  15. 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

  16. Subcellular compartmentation of glutathione in dicotyledonous plants

    PubMed Central

    Müller, 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

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

    PubMed

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

    2015-04-01

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

  18. 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.

  19. Totally Laparoscopic Repair of an Ileal and Uterine Iatrogenic Perforation Secondary to Endometrial Curettage

    PubMed Central

    Vecchio, Rosario; Marchese, Salvatore; Leanza, Vito; Leanza, Antonio; Intagliata, Eva

    2015-01-01

    Small bowel perforation is a unique, serious complication during endometrial biopsy. The authors report a case of a double uterine-ileal perforation totally managed by primary laparoscopic repair. A 63-year-old female was admitted with acute abdomen 2 days after an endometrial curettage. Abdominal X-ray shows signs of pneumoperitoneum. Emergency diagnostic laparoscopy was performed and a uterine-ileal perforation was identified. Repair was accomplished by a totally laparoscopic intracorporeally suturing of the 2 breaches. Postoperative course showed only a delayed ileus and the patient was discharged after 5 days with no complications. When acute abdomen arises following uterine biopsy, a potential iatrogenic intestinal laceration always has to be ruled out. Laparoscopic approach is a quick and safe technique in these cases. Totally laparoscopic primary closure of the iatrogenic ileal laceration may be accomplished with low morbidity. PMID:25692425

  20. Phagocytosis and transcytosis by the follicle-associated epithelium of the ileal Peyer's patch in calves.

    PubMed

    Landsverk, T

    1988-08-01

    Latex beads, 250 and 610 nm in diameter, and parapox virus isolated from ecthyma in sheep, were injected into intestinal loops containing either jejunal or ileal Peyer's patches (PP) of 3-4 week old calves. Uptake of latex and parapox virus was restricted to the ileal PP, 30-60 min after injection. The latex beads seemed to be embraced by thin surface protrusions extending from the concentric folds of the follicle-associated epithelial cells (FAE) of the ileal PP. Both latex and virus were internalized into cytoplasmic vacuoles. Some of the vacuoles containing virus showed reaction for acid phosphatase. The latex beads and virus were shed to the intercellular spaces of the FAE. The exocytosis appeared to occur through specialized indentations of the lateral plasma membrane where the production of 50 nm membrane-bounded particles by budding off from the lateral plasma membrane was a prominent phenomenon.

  1. Large intraluminal ileal hematoma presenting as small bowel obstruction in a child.

    PubMed

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

    2015-04-01

    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.

  2. 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

  3. Linked thioredoxin-glutathione systems in platyhelminths.

    PubMed

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

    2004-07-01

    The thioredoxin and glutathione systems play a central role in thiol-disulfide redox homeostasis in many organisms by providing electrons to essential enzymes, and defence against oxidative stress. These systems have recently been characterized in platyhelminth parasites, and the emerging biochemical scenario is the existence of linked processes with the enzyme thioredoxin glutathione reductase supplying reducing equivalents to both pathways. In contrast to their hosts, conventional thioredoxin reductase and glutathione reductase enzymes appear to be absent. Analysis of published data and expressed-sequence tag databases indicates the presence of linked thioredoxin-glutathione systems in the cytosolic and mitochondrial compartments of these parasites.

  4. Roles for glutathione transferases in antioxidant recycling

    PubMed Central

    Dixon, David P; Steel, Patrick G

    2011-01-01

    Uniquely among the plant glutathione transferases, two classes possess a catalytic cysteine capable of performing glutathione-dependent reductions. These are the dehydroascorbate reductases (DHARs) and the lambda-class glutathione transferases (GSTLs). Using immobilized GSTLs probed with crude plant extracts we have identified flavonols as high affinity ligands and subsequently demonstrated a novel glutathione-dependent role for these enzymes in recycling oxidized quercetin. By comparing the activities of DHARs and GSTLs we now propose a unified catalytic mechanism that suggests oxidized anthocyanidins and tocopherols may be alternative polyphenolic substrates of GSTLs. PMID:21778824

  5. 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

  6. Mucositis management in patients with cancer.

    PubMed

    Keefe, Dorothy M K

    2006-04-01

    Mucositis is an important toxicity to be aware of in anticancer therapy. It contributes to a reduction in cure rates from cancer. Until recently, it has been poorly understood and therefore has not been well managed. It causes patient distress, delays in treatment administration, and reductions in dose intensity, and it costs the health-care system a large amount of money. Mucositis has traditionally been associated more with hematologic malignancies than with solid tumors, because the incidence of severe mucositis has been much higher with the high-dose chemotherapy regimens used in hematologic malignancies. However, the chemotherapy used in solid tumors also causes mucositis and deserves further study. The separation between oral and gastrointestinal mucositis is potentially false and is being removed, with much research now investigating the entire alimentary canal. There are similarities and differences between radiation therapy- and chemotherapy-induced mucositis, and these have implications for treatment and prevention scheduling and type. Risk prediction is another area that requires more work, but there is real hope that, in the future, we might be able to predict who will suffer from mucositis and in which parts of the alimentary canal, thus enabling us to appropriately target the newer antimucotoxic therapies. The Mucositis Study Goup of the Multinational Association for Supportive Care in Cancer has recently published management guidelines for oral and gastrointestinal mucositis and is in the process of updating them. The guidelines serve as an excellent starting place for future mucositis research because they not only review the available treatments but also discuss mechanisms and epidemiology.

  7. 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%).

  8. 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

  9. 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

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

    PubMed

    Mosińska, Paula; Fichna, Jakub; Storr, Martin

    2015-06-28

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

  11. Intestinal mucosal atrophy and adaptation.

    PubMed

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

    2012-11-28

    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.

  12. 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

  13. Mucosal acid causes gastric mucosal microcirculatory disturbance in nonsteroidal anti-inflammatory drug-treated rats.

    PubMed

    Funatsu, Toshiyuki; Chono, Koji; Hirata, Takuya; Keto, Yoshihiro; Kimoto, Aishi; Sasamata, Masao

    2007-01-05

    The mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) suppress gastric mucosal blood flow is not fully understood, although the depletion of mucosal prostaglandin E2 has been proposed as one possible explanation. We investigated the role of gastric acid on gastric mucosal blood flow in NSAID-treated rats. A rat stomach was mounted in an ex vivo chamber, and gastric mucosal blood flow was measured sequentially in a 5-mm2 area of the gastric corpus using a scanning laser Doppler perfusion image system. Results showed that diclofenac (5 mg/kg s.c.) and indomethacin (10 mg/kg s.c.) did not affect gastric mucosal blood flow, although both strongly decreased mucosal prostaglandin E2 when saline was instilled into the gastric chamber. On replacement of the saline in the chamber with 100 mM hydrochloric acid, these drugs caused a decrease in gastric mucosal blood flow levels within 30 min. The specific cyclooxygenase (COX)-2 inhibitors celecoxib (50 mg/kg s.c.) and rofecoxib (25 mg/kg s.c.) did not affect mucosal prostaglandin E2 level, nor did they decrease gastric mucosal blood flow, even when hydrochloric acid was added to the chamber. Furthermore, measurement of vasoconstrictive factors present in the mucosa showed that endothelin-1 levels increased after administration of diclofenac s.c. in the presence of intragastric hydrochloric acid. This indicates that the presence of mucosal hydrochloric acid plays an important role in the NSAID-induced decrease in gastric mucosal blood flow, while the COX-1-derived basal prostaglandin E2, which is unlikely to control gastric mucosal blood flow itself, protects microcirculatory systems from mucosal hydrochloric acid.

  14. Modulation of intestinal mucin composition and mucosal morphology by dietary phytogenic inclusion level in broilers.

    PubMed

    Tsirtsikos, P; Fegeros, K; Kominakis, A; Balaskas, C; Mountzouris, K C

    2012-07-01

    The effect of a dietary phytogenic feed additive (PFA) inclusion level in mucin monosaccharide composition, mucosal morphometry and mucus histochemistry along the broiler intestinal tract was studied. Cobb male broilers (n = 525) were allocated into five experimental treatments that, depending on the type of addition in the basal diet (BD), were labeled as follows: C (BD based on maize-soybean meal with no other additions), E1 (80 mg PFA/kg BD), E2 (125 mg PFA/kg BD), E3 (250 mg PFA/kg of BD) and A (2.5 mg avilamycin/kg BD). Samples from duodenum, ileum and cecum of 14- and 42-day-old broilers were collected and analyzed. In 14-day-old broilers, treatments E2 and E3 had higher (P < 0.01) duodenal mannose than treatments C, E1 and A. Ileal mannose was lower (P < 0.05) in treatment C compared with PFA treatments, and ileal galactose (Gal) was higher (P < 0.01) in treatments E2 and E3 compared with C and A. Polynomial contrast analysis with respect to PFA inclusion level showed that in 14-day-old broilers there was a linear increase (P = 0.001) in duodenal mannose and a quadratic effect (P = 0.038) in duodenal N-acetyl-galactosamine with increasing PFA level. Ileal Gal and mannose increased linearly (P = 0.002 and P = 0.012, respectively) with PFA inclusion level. There were no significant differences between treatments in mucin monosaccharide molar ratios of 42-day-old broilers. However, increasing PFA inclusion level resulted in a linear decrease of ileal fucose (P = 0.021) and cecal N-acetylgalactosamine (P = 0.036). Experimental treatments did not differ (P > 0.05) regarding duodenal villus height (Vh), crypt depth (Cd) and Vh/Cd ratio, irrespective of broiler age and the intestinal segment examined. However, increasing dietary PFA inclusion level showed a pattern of linear increase of duodenal Vh/Cd ratio in 14-day-old broilers and ileal Vh in 42-day-old broilers (P = 0.039 and P = 0.039, respectively). Alcian Blue-Periodic Acid-Schiff (pH 2.5) staining of

  15. Mucosal Vaccine Development Based on Liposome Technology

    PubMed Central

    Norling, Karin; Bally, Marta; Höök, Fredrik

    2016-01-01

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

  16. Treatment of oral mucositis due to chemotherapy

    PubMed Central

    Bagán-Sebastián, José V

    2016-01-01

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

  17. 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.

  18. Animal models of mucositis: implications for therapy.

    PubMed

    Bowen, Joanne M; Gibson, Rachel J; Keefe, Dorothy M K

    2011-01-01

    Alimentary mucositis is a major acute complication in the clinical setting, occurring in a large percentage of patients undergoing cytotoxic therapy. One of the major problems with alimentary mucositis is that the underlying mechanisms behind its development are not entirely understood, which makes it extremely difficult to develop effective interventions. Animal models provide a critical source of knowledge when sampling from patients is unavailable or interventions are yet to be fully tested. This review focuses on the animal models used to increase our understanding of the mechanisms of mucositis and translate new antimucotoxic agents into clinical trials.

  19. 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.

  20. 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.

  1. Rhythms of glutathione peroxidase and glutathione reductase in brain of chick and their inhibition by light.

    PubMed

    Pablos, M I; Reiter, R J; Ortiz, G G; Guerrero, J M; Agapito, M T; Chuang, J I; Sewerynek, E

    1998-01-01

    Melatonin was recently shown to be a component of the antioxidative defense system of organisms due to its free radical scavenging and antioxidant activities. Pharmacologically, melatonin stimulates the activity of the peroxide detoxifying enzyme glutathione peroxidase in rat brain and in several tissues of chicks. In this report, we studied the endogenous rhythm of two antioxidant enzymes, glutathione peroxidase and glutathione reductase, in five regions (hippocampus, hypothalamus, striatum, cortex and cerebellum) of chick brain and correlated them with physiological blood melatonin concentrations. Glutathione peroxidase exhibited a marked 24 h rhythm with peak activity in each brain region which had acrophases about 8 h after lights off and about 4 h after the serum melatonin peak was detected. Glutathione reductase activity exhibited similar robust rhythms with the peaks occurring roughly 2 h after those of glutathione peroxidase. We suggest that neural glutathione peroxidase increases due to the rise of nocturnal melatonin levels while glutathione reductase activity rises slightly later possibly due to an increase of its substrate, oxidized glutathione. The exposure of chicks to constant light for 6 days eliminated the melatonin rhythm as well as the peaks in both glutathione peroxidase and glutathione reductase activities. These findings suggest that the melatonin rhythm may be related to the nighttime increases in the enzyme activities, although other explanations cannot be excluded.

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

    PubMed

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

    2016-07-01

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

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

    DOE PAGES

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

    2014-01-01

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

  4. Clinical application of transanal ileal tube placement using X-ray monitoring

    PubMed Central

    Li, Dechun; Du, Hongtao; Shao, Guoqing; Xu, Yuanshun; Li, Ruihong; Tian, Qingzhong

    2017-01-01

    Colorectal cancer, which includes colon and rectal cancer, is a common digestive tract tumor. Although surgery is the primary form of treatment, there are a number of drawbacks, including patients experiencing considerable pain and high cost. The present study was undertaken to examine the clinical value of transanal ileal tube placement under X-ray monitoring. Thirty-six cases of left colon obstruction presenting to our hospital between July 2011 and February 2014, underwent transanal ileal tube placement using a single-curve catheter guided by a guidewire under X-ray monitoring. An ileal tube was successfully inserted into 32 patients. Clinical symptoms were alleviated effectively within 48 h. Indwelling catheter decompression time was 4–9 days with an average of 5.61 days. In two cases, the colon guidewire perforated into the abdominal cavity. Repeated exploration resistance of the guidewire and catheter indicated stenosis at this position owing to obstruction. In conclusion, transanal placement of the ileal tube through X-ray monitoring is capable of effectively alleviating the symptoms of ileus. Thus, this constitutes a safe, effective, and economical method that is acceptable to patients. PMID:28123533

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

    PubMed Central

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

    2014-01-01

    In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technology was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae, Bacteroidaceae, and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations. PMID:24778651

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

    SciTech Connect

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

    1988-01-01

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

  7. Isolated Ileal Stricture Secondary to Antigen-Negative GI Histoplasmosis in a Patient on Immunosuppressive Therapy

    PubMed Central

    Green, Michael; Nehme, Fredy; Tofteland, Nathan

    2017-01-01

    We present a case of antigen-negative disseminated histoplasmosis manifesting as an isolated ileal stricture in a patient on chronic infliximab and methotrexate. Diagnosis can be challenging due to imperfect tests, and this condition should remain in the differential, even with negative testing. Mortality of untreated disseminated histoplasmosis can be as high as 80%. PMID:28144615

  8. Effect of dietary protein content on ileal amino acid digestibility, growth performance, and formation of microbial metabolites in ileal and cecal digesta of early-weaned pigs.

    PubMed

    Htoo, J K; Araiza, B A; Sauer, W C; Rademacher, M; Zhang, Y; Cervantes, M; Zijlstra, R T

    2007-12-01

    Diarrhea incidence in weaned pigs may be associated with the concentration of intestinal microbial metabolites (ammonia, amines, and VFA) that are influenced by dietary CP content. Three experiments were conducted to determine effects of a low-protein, AA-supplemented diet on ileal AA digestibility, growth performance, diarrhea incidence, and concentration of microbial metabolites in ileal and cecal digesta of pigs weaned at 14 d of age. In Exp. 1, 8 pigs fitted with a simple T-cannula at the distal ileum were assigned in a crossover design to 2 diets containing 24 or 20% CP using wheat, corn, full-fat soybeans, whey powder, fish meal, and blood plasma as the main ingredients. Supplemental AA were added to the diets to meet the AA standards according to the 1998 NRC recommendations. Chromic oxide was used as an indigestible marker. Diets were fed at 2.5 times the ME requirement for maintenance. The reduction of dietary CP decreased (P < 0.05) the apparent ileal digestibility of most AA, except Lys, Met, Thr, Val, and Pro. Dietary CP content did not affect the pH of ileal digesta or ileal concentrations of ammonia N, cadaverine, putrescine, or VFA. In Exp. 2, 8 pigs fitted with a simple T-cannula in the cecum were assigned to 2 diets, similar to Exp. 1. Dietary CP content did not affect the pH of cecal digesta. The reduction in CP content decreased (P < 0.05) cecal ammonia N, acetic acid, isobutyric acid, isovaleric acid, total VFA, and putrescine concentrations by 28 to 39%. In Exp. 3, 32 pigs were assigned to 2 diets, similar to Exp. 1, according to a randomized complete block design. Pigs had free access to feed and water. Dietary CP content did not affect growth performance or fecal consistency scores during the 3-wk study, and diarrhea was not observed. The results of these experiments indicate that lowering the dietary CP content combined with supplementation of AA markedly reduced the production of potentially harmful microbial metabolites in cecal digesta of

  9. Evaluation of apparent ileal digestibility of amino acids in Chinese corn by-products for growing-finishing pigs.

    PubMed

    Liang, Guo; Li, Defa; Wang, Fenglai; Dai, Jianguo; Yang, Wenjun

    2003-04-01

    Twelve crossbred barrows (BW 47 +/- 2.81 kg) were fitted with a T-cannula in the terminal ileum and fed one of ten diets containing corn gluten meal, dried distillers grain or dried distillers grain with solubles as the sole protein source, according to a 6 x 6 Latin Square design. Lysine, tryptophan and methionine were, the first, second and third limiting amino acids in these by-products. The ileal apparent digestibility of methionine, tyrosine, leucine and phenylalanine in corn gluten meal was high. The ileal apparent digestibility of tryptophan, tyrosine and leucine differed significantly in corn gluten meal. The ileal apparent digestibility of amino acids was higher in dried distillers grain with solubles than in dried distillers grain. To predict the ileal apparent digestibility of tryptophan, methionine and threonine linear regression equations were derived. The results suggested that processing technique can influence the ileal apparent digestibility ofamino acids in corn by-products. It was concluded that the direct technique cannot accurately determine the ileal apparent digestibility of tryptophan in dried distillers grain with solubles and dried distillers grain, due to its low content. The content of an amino acid in a feedstuff used as the sole source of protein must meet the minimum requirement of pigs when the ileal apparent digestibility of constituent amino acids is determined using the direct technique.

  10. Targeting Mucosal Healing in Crohn's Disease

    PubMed Central

    Kakkar, Aarti; Wasan, Sharmeel K.

    2011-01-01

    The goal of medical treatment for Crohn's disease includes improving patients' quality of life while reducing the need for hospitalization and surgery. The current medical armamentarium includes 5-aminosalicylates, corticosteroids, immunomodulators, and biologic agents. In the past, response to treatment was measured by clinical improvement in symptoms; however, with the advent of disease-modifying medications, mucosal healing has emerged as an increasingly important goal of therapy. Mucosal healing, or endoscopic remission, is associated with increased rates of clinical remission, fewer hospitalizations, and fewer abdominal surgeries. Both the immunomodulator and biologic classes of medications are effective at inducing mucosal healing. Despite several limitations, mucosal healing has become a desirable and valid measure of disease activity. PMID:21869869

  11. 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.

  12. A regenerative approach towards mucosal fenestration closure.

    PubMed

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

    2013-06-06

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

  13. 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

  14. Mucosal Vaccination against Tuberculosis Using Inert Bioparticles

    PubMed Central

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

    2013-01-01

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

  15. Ileostomy for Non-Traumatic Ileal Perforations: Is this the Beginning of the End?

    PubMed Central

    Babu, Rajashekara Gangappa; Chowdary, Prashanth Basappa

    2016-01-01

    Introduction Ileal perforations are a common place of occurrence in emergency operation rooms around India. They are also significant contributors to mortality in our country. They are very distressing for patients because of the high morbidity of a laparotomy and in certain cases a stoma if its necessity is felt by the operating surgeon. The nature of the disease itself predisposes to a number of complications including wound infections, faecal fistulas and complications associated with a stoma. Aim To evaluate the role of ileostomy in patients with non-traumatic ileal perforation. Materials and Methods A total of 192 cases of ileal perforation, diagnosed per-operatively, were prospectively studied between June 2012 and July 2014. Cases were treated according to standard resuscitation protocols and underwent repair of the ileal perforation either as primary closure or as a bowel resection and anastomosis with or without a proximal diversion ileostomy. Cases were followed up for a period of six months and immediate and late complications and outcomes were noted. Results A total of 192 patients were studied during the given study period out of which 170 (88.5%) were males. The disease was treated primarily without diversion stoma in 176 patients and in 16 patients a proximal diversion ileostomy was performed. The overall mortality was 15 (7.8%) that was noted to be not significantly different in patients with respect to the performance of a stoma. Enterocutaneous fistula was a complication seen exclusively in the non-ileostomy group whereas stomal complications were expectedly noted only in the stoma group. Conclusion The authors found that though conventional ileostomy diversion may appear a safe option in patients with ileal perforations, it has its own additional morbidity, which at times can be very difficult to manage. An ileostomy is of use in a very small group of patients that is diminishing as better facilities and equipment are obtained to manage this

  16. 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.

  17. Corneal endothelial glutathione after photodynamic change

    SciTech Connect

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

    1982-03-01

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

  18. 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

  19. Impaired glutathione synthesis in neurodegeneration.

    PubMed

    Aoyama, Koji; Nakaki, Toshio

    2013-10-18

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

  20. Impaired Glutathione Synthesis in Neurodegeneration

    PubMed Central

    Aoyama, Koji; Nakaki, Toshio

    2013-01-01

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

  1. 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

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

    PubMed

    Lærke, 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 mPa·s in the control diet (NX) to 6.0 mPa·s ( < 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 mPa·s) than with fine and coarse wheat (<1.7 mPa·s). 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

  3. Transfer across mucosal epithelium, tissue content and metabolic fate of 125I-(ipodate-sodium) on isolated everted segments of rat small intestine.

    PubMed

    Komp, B; Forth, W

    1980-04-01

    1. Transfer and tissue content of 125I-radioactivity was measured after administration of 125I-(ipodate-sodium) to everted rat jejunal segments. 2. After having administered 10(-5) M 125I-(ipodate-sodium) on both sides of the everted sacs the S/M ratio of the concentration of 125I-radioactivity was 1.5 in jejunal segments and 2.3 in ileal segments. The tissue content was nearly equal for both segments. According to the apparent partition coefficient for ipodate-sodium at pH 7, the 125I-radioactivity is accumulated in the tissue about 10-fold. 3. Lowering of the temperature of the incubation medium from 37 degrees C to 15 degrees C prevents the building up of a concentration gradient between the serosal and the mucosal side on either jejunal and ileal segments whereas the tissue content of 125I-radioactivity was nearly unchanged. 4. With increasing concentrations (1.6--10(-6)--9.6-10(-4) M) of 125I-(ipodate-sodium) administered on the mucosal side the transfer and the tissue content of 125I-radioactivity were decreased. This appears to be a toxic effect since in jejunal segments also the S/M ratio for the concentration of glucose decreases. 5. The analysis of the 125I-radioactivity in the serosal fluid of jejunal segments showed that the bulk of the 125I-radioactivity was present in the aqueous phase and only 33% as the unchanged ipodate-sodium in the organic phase. 10% of the 125I-radioactivity must be attributed to inorganic iodine. The concentration of 125I-(ipodate-sodium) administered in the mucosal fluid only was 3.2-10(-6) M. At lower temperature (7 degrees C) the bulk of the 125I-radioactivity in the serosal fluid was found in the organic phase, i.e. as unchanged ipodate-sodium. 6. After the incubation of the aqueous phase with beta-glucuronidase or NaOH about 97% of the 125I-radioactivity could be extracted into the organic phase. This means that the bulk of the 125I-radioactivity in the aqueous phase is present as a conjugate, e.g. ester glucuronide of the

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

    PubMed

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

    2007-02-01

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

  5. Complications of the ileal pouch: is the pouchogram a useful predictor?

    PubMed

    Malcolm, P N; Bhagat, K K; Chapman, M A; Davies, S G; Williams, N S; Murfitt, J B

    1995-09-01

    A series of ileal pouchograms from 25 consecutive patients has been analysed retrospectively. Ileal pouchography may demonstrate abnormalities which delay closure of the covering ileostomy. The aim was to determine whether disruption of the ileoanal anastomosis and/or leak at pouchography correlated with pelvic sepsis after ileostomy closure. Disruption of the stapled ileoanal anastomosis is a sensitive (88%) but not specific predictor (57%) for subsequent pelvic sepsis. The predictive value of a negative test is high (89%). Leak of contrast from the anastomosis is specific (81%) but not sensitive (56%) for pelvic sepsis. No significant relationship was demonstrated between width of the presacral space and the presence of pelvic sepsis. No significant relationship was demonstrated between diameter of the ileoanal anastomosis and symptoms of stricture. The presence of anastomotic disruption or leak at pouchography prior to ileostomy closure are useful predictors of potential pelvic sepsis.

  6. Spontaneous Perforation as a First Presentation of Ileal Gastrointestinal Stromal Tumour (GIST) with Synchronous Breast Sarcoma.

    PubMed

    Sharma M, Bir Kumar; Barad, Arun Kumar; Padu, Kemba; Singh K, Sridartha; Singh Th, Sudhir Chandra

    2014-05-01

    Gastrointestinal Stromal Tumours (GIST's) are the most common mesenchymal neoplasms of the gastrointestinal tract. Majority of the GISTs are asymptomatic and often diagnosis is incidental. Synchronous second malignancies have been reported in patients with GIST. We report a case of 50-year-old female presenting with features of hollow viscous perforation, found to have ileal GIST with perforations along with a synchronous breast sarcoma. GIST with spontaneous perforation as its first clinical manifestation is rare. Synchronous occurrence of an ileal GIST with a breast sarcoma is unique and deserves reporting. This case report highlights the varied nature of clinical presentation of the GIST and also stresses on the importance of extensive search for the synchronous second malignancies in the extra abdominal sites as well.

  7. 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

  8. [Ureteral replacement using an ileal graft of reduced diameter. A preliminary report].

    PubMed

    Rampal, M; Rossi, D; Coulange, C; Bentolila, E; Masson, J; Vaillant, J L

    1991-02-01

    Extensive or even complete loss of the ureter of a functioning kidney makes it impossible to restore the normal continuity of the urinary tract by any available surgical technique. An ileal loop of appropriate length, anastomosed to the bladder with its entire lumen, is the only tissue suitable for replacing this missing ureter; this results in the formation of a megaureter or a vesical diverticulum which, although contractile, presents dimensions and conditions of anastomosis which predispose to the development of vesico-ileal reflux and a risk of torpid infection and dangerous reabsorption of the urine. We consider that it would be useful to use the ileum to create a contractile, reduced calibre tube with properties similar to those of the ureter. This technique, which has rare indications, is feasible as illustrated by the 5 cases reported here, corresponding to 7 uretero-ileoplasties modelled according to this technique. Results were satisfactory with a follow up of 6-24 months.

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

    PubMed

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

    2016-02-01

    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.

  10. Recovery of intestinal membrane binding sites for K88 E. coli from pig mucosal organ cultures.

    PubMed

    Wilson, I B; Staley, T E; Bush, L J; Gilliland, S E

    1984-04-01

    Putative receptors for K88 + E. coli from piglet intestinal epithelium were released into the organ culture medium and were demonstrated by direct binding with K88 + E. coli through the utilization of an in vitro binding procedure or by immunoprecipitation with K88 antigen. Incorporation of 14C-glucosamine by newborn to day old and 3-week to 6-week old piglet jejunal and ileal mucosa, in organ culture, occurred throughout the 24 hr culture period. Uptake in both age groups and both areas of the intestine was similar with a somewhat greater incorporation by the older age group. Secretion of 14C-glucosamine-labeled components into the culture medium was demonstrated by gel filtration of the concentrated medium. Some large molecular weight components eluted in the void volume in excess of 2 X 10(6) daltons. A second peak of activity was spread from approximately 690K to 25K daltons. All eluted fractions demonstrated binding to K88 + E. coli. Antibodies to purified brush borders from susceptible pigs produced prominent precipitation bands following double diffusion with concentrated organ culture media which confirmed that the organ culture media contained labeled proteins of brush border origin. Immunoprecipitation of the intestinal mucosal organ culture media with K88 + pili and pilus antisera, followed by electrophoresis with SDS and reduced conditions, demonstrated a subunit of approximately 35K daltons.

  11. Mucosal Immunity and Candida albicans Infection

    PubMed Central

    Moyes, David L.; Naglik, Julian R.

    2011-01-01

    Interactions between mucosal surfaces and microbial microbiota are key to host defense, health, and disease. These surfaces are exposed to high numbers of microbes and must be capable of distinguishing between those that are beneficial or avirulent and those that will invade and cause disease. Our understanding of the mechanisms involved in these discriminatory processes has recently begun to expand as new studies bring to light the importance of epithelial cells and novel immune cell subsets such as Th17 T cells in these processes. Elucidating how these mechanisms function will improve our understanding of many diverse diseases and improve our ability to treat patients suffering from these conditions. In our voyage to discover these mechanisms, mucosal interactions with opportunistic commensal organisms such as the fungus Candida albicans provide insights that are invaluable. Here, we review current knowledge of the interactions between C. albicans and epithelial surfaces and how this may shape our understanding of microbial-mucosal interactions. PMID:21776285

  12. C. albicans Colonization of Human Mucosal Surfaces

    PubMed Central

    Southern, Peter; Horbul, Julie; Maher, Diane; Davis, Dana A.

    2008-01-01

    Background Candida albicans is a low level commensal organism in normal human populations with the continuous potential to expand and cause a spectrum of clinical conditions. Methodology/Principal Findings Using ex vivo human organ cultures and populations of primary human cells, we have developed several related experimental systems to examine early-stage interactions between C. albicans and mucosal surfaces. Experiments have been conducted both with exogenously added C. albicans and with overtly normal human mucosal surfaces supporting pre-existing infections with natural isolates of Candida. Under different culture conditions, we have demonstrated the formation of C. albicans colonies on human target cells and filament formation, equivalent to tissue invasion. Conclusions/Significance These organ culture systems provide a valuable new resource to examine the molecular and cellular basis for Candida colonization of human mucosal surfaces. PMID:18446191

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. 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

  15. Surgical Clips Migration up to Renal Collecting System from Ileal Conduit Postcystectomy

    PubMed Central

    Albadawi, Hani; Sener, Tarik Emre

    2016-01-01

    Abstract This is a 49-year-old female known to have had cystectomy and ileal conduit 4 years ago presented to our hospital complaining of left flank pain with recurrent urinary tract infection. Radiologic investigations showed left lower pole renal stone. She underwent left laser flexible ureterorenoscopy. Renal collection system was fully explored that showed stone occupying the lower calix, laser disintegration of the stone revealed what we assumed are surgical clips. PMID:28078327

  16. Effect of dietary oligochitosan supplementation on ileal digestibility of nutrients and performance in broilers.

    PubMed

    Huang, R L; Yin, Y L; Wu, G Y; Zhang, Y G; Li, T J; Li, L L; Li, M X; Tang, Z R; Zhang, J; Wang, B; He, J H; Nie, X Z

    2005-09-01

    The effect of dietary chitosan oligosaccharides (COS) supplementation on ileal digestibilities of nutrients and performance in broilers was assessed by feeding graded levels (0, 50, 100, 150 mg/kg) of COS. Two thousand four hundred male commercial Avian broilers (1-d-old) were assigned randomly to 5 dietary treatment groups (60 birds per pen with 8 pens per treatment). Diet A was a typical corn- and soybean meal-based diet supplemented with 6 mg/kg of an antibiotic flavomycin (positive control). Diet B was the basal diet without any supplement. Diets C, D, and E were formulated by adding 50, 100, and 150 mg/kg of COS to the basal diet, respectively. On the morning of d 21 and 42, 64 birds (8 per pen with 8 pens per treatment) from the growth trial for each age group were killed by cervical dislocation for determination of the ileal digestibilities of nutrients. Dietary supplementation with COS and antibiotic enhanced (P < 0.05) the ileal digestibilities of DM, Ca, P, CP, and all amino acids (except for alanine in the 21-d-old birds or phenylalanine, glutamate, and glycine for the 42-d-old birds). Feed efficiency was improved (P < 0.05) in response to dietary supplementation of an antibiotic or COS (150 mg/kg for d 1 to 21, and 100 and 150 mg/kg for d 21 to 42). The results demonstrate for the first time to our knowledge that dietary COS supplementation was effective in increasing the ileal digestibilities of nutrients and feed efficiency in broilers. Our findings may explain a beneficial effect of COS on chicken growth performance.

  17. Adrenergic denervation hypersensitivity in ileal circular smooth muscle after small bowel transplantation in rats.

    PubMed

    Shibata, C; Balsiger, B M; Anding, W J; Sarr, M G

    1997-11-01

    Effects of small bowel transplantation (SBT) on ileal motility are unknown. The aim of the present study was to investigate changes in spontaneous contractile activity and sensitivity to cholinergic and adrenergic agents in the ileal circular muscle after SBT in rats. Orthotopic SBT was performed in syngeneic rats to avoid immune phenomena. Distal ileal circular muscle strips from rats one week (N = 10) and eight weeks (N = 10) after SBT were stretched to optimal length (Lo), and basal spontaneous activity at Lo was measured. Dose-response experiments to the cholinergic agonist bethanechol (Be, 10(-8)-10(-4) M) were performed in the presence of tetrodotoxin (TTX, 10(-6) M) and to the adrenergic agonist norepinephrine (NE, 10(-8)-10(-4) M) with or without TTX. ED50 (negative log of drug-concentration that induced 50% effect) was calculated. We also studied rats with selective jejunoileal ischemia/ reperfusion, intestinal transection/reanastomosis, naive controls, and sham operated controls (N > or = 8/group). Spontaneous basal activity did not differ among groups. Sensitivity to Be was not different in rats after SBT or in other groups compared to control tissue. After SBT, hypersensitivity to NE was shown by a significant increase of ED50 at one and eight weeks after SBT (5.1 +/- 0.3 vs 6.2 +/- 0.4 and 6.2 +/- 0.2, respectively; P < 0.05) regardless of the presence of TTX. No hypersensitivity was observed after ischemia-reperfusion intestinal transection-reanastomosis, or sham operation. It is concluded that ileal hypersensitivity to NE was related to the extrinsic denervation obligated by the transplantation procedure, possibly mediated through an increase in number of receptors on smooth muscle, not on the enteric nerves.

  18. Pregnancy and delivery in a patient with a Studer orthotopic ileal neobladder

    PubMed Central

    Kołodziej, Anna; Tupikowski, Krzysztof; Małkiewicz, Bartosz; Dembowski, Janusz; Zimmer, Mariusz; Szydełko, Tomasz; Zdrojowy, Romuald

    2016-01-01

    Pregnancies in patients after cystectomy with urinary diversion, especially after the construction of a continent urinary reservoir, are rare. Experience in this field is limited and mainly concerns patients with congenital disorders, neurogenic diseases or trauma. In this paper, we report the outcome of pregnancy, delivery and the postpartum period in a 27-year old woman with a Studer ileal orthotopic neobladder after radical cystectomy, performed after the diagnosis of a malignant tumor at the age of 14. PMID:28127463

  19. The Glutathione System of Aspergillus nidulans Involves a Fungus-specific Glutathione S-Transferase*S⃞

    PubMed Central

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

    2009-01-01

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

  20. Ileo-ileal intussusception caused by lymphangioma of the small bowel treated by single-incision laparoscopic-assisted ileal resection

    PubMed Central

    Kohga, Atsushi; Kawabe, Akihiro; Hasegawa, Yuto; Yajima, Kiyoshige; Okumura, Takuya; Yamashita, Kimihiro; Isogaki, Jun; Suzuki, Kenji; Komiyama, Akira

    2017-01-01

    Intraabdominal lymphangiomas are uncommon; additionally, those affecting the gastrointestinal tract are rare and account for less than 1% of cases. Intussusception caused by a cystic lymphangioma of the small bowel is extremely rare. The patient was a 20-year-old woman who visited our emergency room with a complaint of abdominal pain. A computed tomography image revealed ileo-ileal intussusception with a leading hypovascular mass measuring 1 cm in a diameter. Single-incision laparoscopic-assisted ileal resection was performed. The surgical specimen consisted of a soft polycystic mass. Macroscopically, a pedunculated polyp with a convolutional pattern was found. Microscopically, the inner surfaces of the cysts were covered with a single layer of endothelial cells. On immunohistochemical examination, the endothelial cells were partially positive for D2-40 and CD34. Smooth muscle cells were also found around the cysts. The lesion was diagnosed as a cystic lymphangioma. Dozens of cases of small bowel lymphangiomas have previously been reported. Of these, cases with intussusception were very rare. This is the first case of small bowel intussusception due to lymphangioma treated by single-incision laparoscopic-assisted surgery. PMID:28104992

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Fan, Weiwei; Yu, Yang; Shu, Junjie; Ming, Hao; Li, Weiping; Fan, Zhilu

    2015-08-01

    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.

  3. 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

  4. [Caerulein-induced contraction of the ileal longitudinal smooth muscle isolated from various animal species].

    PubMed

    Shimizu, K; Horiuchi, T; Tamiya, K; Nakajyo, S

    1983-04-01

    An effect of caerulein was studied on a contractile response of the ileal longitudinal smooth muscle isolated from seven animal species, monkey, dog, rabbit, guinea-pig, rat, vole and mouse. In isotonic recording, caerulein induced a contraction in the muscle isolated from all animal species. Sensitivities of ileal strips to caerulein in the contractile response was divided into three groups. That is, a high sensitive group; dog and guinea-pig, a middle sensitive group; rabbit and vole, a low sensitive group; monkey, rat and mouse. In another series of experiment, effect of several antagonists was examined on the caerulein-induced contraction in ileal muscle of dog, rabbit or guinea-pig. TTX inhibited the contractions in all the ilea. As the contraction was inhibited by atropine and scopolamine in dog ileum but not in rabbit one, the contraction may be due to an excitation of the cholinergic neuron or an excitation of non-cholinergic excitatory neuron, respectively. On the other hand, it is supposed that the contraction in guinea-pig ileum is involved to both the neurons because the contraction was inhibited partially by scopolamine and not by atropine. In conclusion, the ilea isolated from seven animal species showed species differences in sensitivity to caerulein in contractile response, and caerulein seems induces the contractions involving to different nervous systems in dog, rabbit or guinea-pig ileum, respectively.

  5. Restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis: A narrative review

    PubMed Central

    Sofo, Luigi; Caprino, Paola; Sacchetti, Franco; Bossola, Maurizio

    2016-01-01

    Restorative proctocolectomy with ileal pouch-anal anastomosis (RP-IPAA) is the gold standard surgical treatment for ulcerative colitis. However, despite the widespread use of RP-IPAA, many aspects of this treatment still remain controversial, such as the approach (open or laparoscopic), number of stages in the surgery, type of pouch, and construction type (hand-sewn or stapled ileal pouch-anal anastomosis). The present narrative review aims to discuss current evidence on the short-, mid-, and long-term results of each of these technical alternatives as well as their benefits and disadvantages. A review of the MEDLINE, EMBASE, and Ovid databases was performed to identify studies published through March 2016. Few large, randomized, controlled studies have been conducted, which limits the conclusions that can be drawn regarding controversial issues. The available data from retrospective studies suggest that laparoscopic surgery has no clear advantages compared with open surgery and that one-stage RP-IPAA may be indicated in selected cases. Regarding 2- and 3-stage RP-IPAA, patients who underwent these surgeries differed significantly with respect to clinical and laboratory variables, making any comparisons extremely difficult. The long-term results regarding the pouch type show that the W- and J-reservoirs do not differ significantly, although the J pouch is generally preferred by surgeons. Hand-sewn and stapled ileal pouch-anal anastomoses have their own advantages, and there is no clear benefit of one technique over the other. PMID:27648159

  6. Disconnection, pouch revision and reconnection of the ileal pouch-anal anastomosis.

    PubMed

    Sagar, P M; Dozois, R R; Wolff, B G; Kelly, K A

    1996-10-01

    The aim of this retrospective study was to determine the outcome of patients with a dysfunctional pelvic ileal reservoir in whom disconnection of an ileal pouch-anal anastomosis (IPAA), pouch revision and reanastomosis had been carried out. There were 23 patients (15 women). At the revision operation functional problems were found to be due to a long efferent spout (nine patients), sepsis and/or fistula (four), a redundant blind limb (three), a twisted pouch (three), anastomotic problems (three) or no reservoir (one). The pouch was salvaged in 16 patients and a new pouch was constructed in seven. The pouch-anal anastomosis was resutured in 22 patients and stapled in one. Postoperative complications (all minor) occurred in six patients. Two patients underwent two revision of IPAA. At a median follow-up of 5 (range 1-10) years, 11 patients reported good to excellent function, five reported fair function and one reported recurrent pouchitis. Revision surgery was unsuccessful in six of 23 patients (three had gross incontinence, two excessive bowel movements and one Crohn's disease), and they subsequently underwent pouch excision. It is concluded that revision of an ileal reservoir and IPAA can be undertaken safely with good results in carefully selected patients.

  7. 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

  8. Restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis: A narrative review.

    PubMed

    Sofo, Luigi; Caprino, Paola; Sacchetti, Franco; Bossola, Maurizio

    2016-08-27

    Restorative proctocolectomy with ileal pouch-anal anastomosis (RP-IPAA) is the gold standard surgical treatment for ulcerative colitis. However, despite the widespread use of RP-IPAA, many aspects of this treatment still remain controversial, such as the approach (open or laparoscopic), number of stages in the surgery, type of pouch, and construction type (hand-sewn or stapled ileal pouch-anal anastomosis). The present narrative review aims to discuss current evidence on the short-, mid-, and long-term results of each of these technical alternatives as well as their benefits and disadvantages. A review of the MEDLINE, EMBASE, and Ovid databases was performed to identify studies published through March 2016. Few large, randomized, controlled studies have been conducted, which limits the conclusions that can be drawn regarding controversial issues. The available data from retrospective studies suggest that laparoscopic surgery has no clear advantages compared with open surgery and that one-stage RP-IPAA may be indicated in selected cases. Regarding 2- and 3-stage RP-IPAA, patients who underwent these surgeries differed significantly with respect to clinical and laboratory variables, making any comparisons extremely difficult. The long-term results regarding the pouch type show that the W- and J-reservoirs do not differ significantly, although the J pouch is generally preferred by surgeons. Hand-sewn and stapled ileal pouch-anal anastomoses have their own advantages, and there is no clear benefit of one technique over the other.

  9. Oral mucosal diseases: evaluation and management.

    PubMed

    Stoopler, Eric T; Sollecito, Thomas P

    2014-11-01

    Oral mucosal diseases encompass several common conditions that affect the general population. Some of these disorders present with signs and symptoms that are pathognomonic for the condition, whereas others present with similar features that can make clinical diagnosis difficult to achieve. It is important for physicians to have a clear understanding of these disorders to provide appropriate care to patients. This article reviews clinical aspects of common oral mucosal disorders, including candidiasis, herpes simplex viral infections, aphthous stomatitis, lichen planus, pemphigus vulgaris, and mucous membrane pemphigoid.

  10. 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.

  11. Concomitant early mucosal and cutaneous leishmaniasis in Brazil.

    PubMed

    Boaventura, Viviane S; Cafe, Virginia; Costa, Jackson; Oliveira, Fabiano; Bafica, Andre; Rosato, Andrea; de Freitas, Luiz A R; Brodskyn, Claudia; Barral-Netto, Manoel; Barral, Aldina

    2006-08-01

    Mucosal leishmaniasis (ML) is often clinically silent until reaching a highly advanced state. In this prospective study, 6 of 220 patients with early cutaneous leishmaniasis were diagnosed with mucosal involvement by otorhinolaryngological examination (a rate similar to the reported rate of late ML). Detection of early ML may represent an important strategy in preventing severe mucosal destruction in human leishmaniasis.

  12. 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-γ, 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

  13. 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

  14. Mucosal melanoma of the head and neck.

    PubMed

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

    2017-04-01

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

  15. Characterization of Mucosal Candida albicans Biofilms

    PubMed Central

    Dongari-Bagtzoglou, Anna; Kashleva, Helena; Dwivedi, Prabhat; Diaz, Patricia; Vasilakos, John

    2009-01-01

    C. albicans triggers recurrent infections of the alimentary tract mucosa that result from biofilm growth. Although the ability of C. albicans to form a biofilm on abiotic surfaces has been well documented in recent years, no information exists on biofilms that form directly on mucosal surfaces. The objectives of this study were to characterize the structure and composition of Candida biofilms forming on the oral mucosa. We found that oral Candida biofilms consist of yeast, hyphae, and commensal bacteria, with keratin dispersed in the intercellular spaces. Neutrophils migrate through the oral mucosa and form nests within the biofilm mass. The cell wall polysaccharide β-glucan is exposed during mucosal biofilm growth and is more uniformly present on the surface of biofilm organisms invading the oral mucosa. We conclude that C. albicans forms complex mucosal biofilms consisting of both commensal bacterial flora and host components. These discoveries are important since they can prompt a shift of focus for current research in investigating the role of Candida-bacterial interactions in the pathogenesis of mucosal infections as well as the role of β-glucan mediated signaling in the host response. PMID:19956771

  16. Glutathione Metabolism and Parkinson’s Disease

    PubMed Central

    Smeyne, Michelle

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  18. Management of Mucositis During Chemotherapy: From Pathophysiology to Pragmatic Therapeutics.

    PubMed

    Van Sebille, Ysabella Z A; Stansborough, Romany; Wardill, Hannah R; Bateman, Emma; Gibson, Rachel J; Keefe, Dorothy M

    2015-11-01

    Chemotherapy-induced mucositis is a common condition caused by the breakdown of the mucosal barrier. Symptoms can include pain, vomiting and diarrhoea, which can often necessitate chemotherapy treatment breaks or dose reductions, thus compromising survival outcomes. Despite the significant impact of mucositis, there are currently limited clinically effective pharmacological therapies for the pathology. New emerging areas of research have been proposed to play key roles in the development of mucositis, providing rationale for potential new therapeutics for the prevention, treatment or management of chemotherapy-induced mucositis. This review aims to address these new areas of research and to comment on the therapeutics arising from them.

  19. 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.

  20. 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

  1. Nutritional evaluation of biologically treated white kidney beans (Phaseolus vulgaris L.) in pigs: ileal and amino acid digestibility.

    PubMed

    Schulze, H; Savelkoul, F H; Verstegen, M W; van der Poel, A F; Tamminga, S; Groot Nibbelink, S

    1997-12-01

    We studied the effect of feeding young growing pigs a semisynthetic diet containing 7.5% white kidney beans-germinated (GB), pancreatin treated (PTB), or untreated (raw beans RB)--on protein and amino acid (AA) digestibilities at the terminal ileum. Eleven castrated male pigs (12.2 kg live weight) fitted with a post-valve T-cecal cannula and two blood catheters were used. The 15N-isotope dilution method was used to determine the amount of endogenous protein passing the terminal ileum and the true ileal protein digestibility. Ileal crude protein losses in pigs fed the RB, GB, and PTB diets were 51.9, 27.4, and 51.1 g/kg of DMI, respectively. The total amounts of AA passing the terminal ileum of the pigs fed the RB, GB, and PTB diets were 48.6, 21.4, and 42.2 g/kg DMI, respectively. The apparent ileal crude protein and AA digestibilities of the RB, GB, and PTB diets were 74, 87, and 75% and 76, 89, and 78%, respectively. True ileal protein digestibilities were 88, 93, and 93% for the RB, GB, and PTB diets, respectively. On the basis of this research, germination of white kidney beans improves the digestion of protein by decreasing the content of bean antinutritional factors and increasing the bean true ileal protein digestibility.

  2. Endoscopic closure instead of surgery to close an ileal pouch fistula with the over-the-scope clip system

    PubMed Central

    Wei, Yao; Gong, Jian-Feng; Zhu, Wei-Ming

    2017-01-01

    An ileal pouch fistula is an uncommon complication after an ileal pouch anal anastomosis. Most patients who suffer from an ileal pouch fistula will need surgical intervention. However, the surgery can be invasive and has a high risk compared to endoscopic treatment. The over-the-scope clip (OTSC) system was initially developed for hemostasis and leakage closure in the gastrointestinal tract during flexible endoscopy. There have been many successes in using this approach to apply perforations to the upper gastrointestinal tract. However, this approach has not been used for ileal pouch fistulas until currently. In this report, we describe one patient who suffered a leak from the tip of the “J” pouch and was successfully treated with endoscopic closure via the OTSC system. A 26-year-old male patient had an intestinal fistula at the tip of the “J” pouch after an ileal pouch anal anastomosis procedure. He received endoscopic treatment via OTSC under intravenous anesthesia, and the leak was closed successfully. Endoscopic closure of a pouch fistula could be a simpler alternative to surgery and could help avoid surgery-related complications. PMID:28250903

  3. Glutathione synthesis is essential for pollen germination in vitro

    PubMed Central

    2011-01-01

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

  4. New generation of oral mucosal vaccines targeting dendritic cells

    PubMed Central

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

    2013-01-01

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

  5. New generation of oral mucosal vaccines targeting dendritic cells.

    PubMed

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

    2013-12-01

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

  6. The role of the gut hormone GLP-1 in the metabolic improvements caused by Ileal Transposition

    PubMed Central

    Gaitonde, Shrawan; Kohli, Rohit; Seeley, Randy

    2011-01-01

    Bariatric surgery alters the gastrointestinal hormonal milieu leading to improved glucose homeostasis, though the mechanism leading to these changes is poorly understood. Ileal transposition (IT) is a procedure that is neither restrictive nor malabsorptive but nevertheless produces profound improvements in glucose regulation. Ileal transposition involves a short segment of distal ileum being transposed to the proximal jejunum in an isoperistaltic direction thereby avoiding any gastric resection or intenstinal bypass. Methods Diet-induced obese rats underwent either Ileal Transposition (IT), or Sham procedures. The Sham operated rats were pair fed to the IT surgical group to control for the effects of reduced food intake. Body composition data was recorded at specific time points, and glucose tolerance tests were performed at 5 and 6 weeks both in the presence and absence of Exendin 9–39, a known glucose-like peptide 1 (GLP-1) receptor antagonist. A subset of Naïve rats were also maintained for comparison. Results IT and Sham operated rats had no differences in food intake and body weight however, IT rats had a significant decrease in their body fat composition (P<0.05). No difference existed in glucose tolerance when exposed to an intrapertioneal glucose load, however, IT rats showed markedly improved glucose tolerance when submitted to an oral glucose tolerance test (p<0.001). Blocking GLP-1 receptors reversed these important improvements in rats with IT surgery. Conclusions The present work recapitulates what is seen in rodents and humans that IT improves glucose tolerance and body composition. The present data provide compelling evidence that these improvements are a product of increased GLP-1 secretion that results from placing the key GLP-1 secreting cells closer to chyme coming from the stomach. Such data support the notion that rather than restriction or malabsorption, the underling molecular mechanisms that mediate the potent improvements produced by

  7. Effects of mercury on glutathione and glutathione-dependent enzymes in hares (Lepus europaeus Pallas).

    PubMed

    Linšak, Željko; Linšak, Dijana Tomić; Špirić, Zdravko; Srebočan, Emil; Glad, Marin; Milin, Čedomila

    2013-01-01

    The aim of this study was to analyze and evaluate risks of long-term exposure to mercury in hares (Lepus europaeus Pallas), with a chemical-analytical approach evaluating median mass fraction of toxic mercury in the hares organs (liver, kidney, muscle and brain). To obtain better insight into possible effects of mercury, the study included screening of the oxidative status after long term exposure to low concentrations of mercury. Hares organs were analyzed for total mercury concentration by AAS. Glutathione and glutathione-dependent enzymes status was also investigated. The median mercury concentrations (wet weight) in the liver, kidney, muscle and brain of the hares ranged from 0.058-0.189, 0.138-0.406, 0.013-0.046 and 0.022-0.102 μg/g respectively. Concentration of the glutathione (GSH), glutathione-peroxidase (GPx), and glutathione-reductase (GR) activity increased with the mercury concentration. However, glutathione S-transferase (GST) and superoxide-dismutase (SOD) activity decreased with the mercury concentration. The results of this study show the impact of environmentally absorbed mercury on the antioxidant status of the examined hares. Further research on long-term exposure to low concentrations of mercury is needed.

  8. Development of ileal cytokine and immunoglobulin expression levels in response to early feeding in broilers and layers.

    PubMed

    Simon, K; de Vries Reilingh, G; Kemp, B; Lammers, A

    2014-12-01

    Provision of feed in the immediate posthatch period may influence interaction between intestinal microbiota and immune system, and consequently immunological development of the chick. This study addressed ileal immune development in response to early feeding in 2 chicken breeds selected for different production traits: broilers and layers. Chicks of both breeds either received feed and water immediately posthatch or were subjected to a 72-h feed and water delay. Ileal cytokine and immunoglobulin mRNA expression levels were determined at different time points. Effects of early feeding were limited, but breeds differed strikingly regarding cytokine and immunoglobulin expression levels. Cytokine expression levels in broilers were low compared with layers and showed a transient drop in the second to third week of life. In contrast, broilers showed considerably higher expression levels of IgA, IgM, and IgY. These findings indicate that the 2 breeds use different immune strategies, at least on the ileal level.

  9. Divergent modulation of swine ileal microbiota by formic acid and methionine hydroxy analogue-free acid.

    PubMed

    Apajalahti, J; Rademacher, M; Htoo, J K; Redshaw, M; Kettunen, A

    2009-06-01

    Management of intestinal microbiota of monogastric animals has increased in importance since the ban of growth promoting antibiotics in many countries. Organic acids have been used as alternatives to antibiotics by many feed manufacturers. Regardless of the wide usage, the effect, dose response and mode of action of acids on intestinal microbes is poorly understood. In this study, we investigated the effects of dietary supplementation of three commonly used products, namely formic acid (FA) (90%), dl-methionine (DLM) (99%) and liquid methionine hydroxy analogue-free acid (88%), on ileal microbiota of pigs. Laboratory simulation system, mimicking swine ileum, was used to study the products at various concentrations and combinations. Furthermore, selected combinations were tested in a piglet trial to confirm the findings made in in vitro studies. FA turned out to have a dual effect on ileal microbiota. At concentrations below 0.5%, it significantly stimulated bacteria, but at higher inclusion rates it was highly inhibitory. This finding, which was consistent in in vitro and in vivo studies, implies that reducing the dose of FA does not lead to a diluted inhibitory effect, but in fact, an opposite, stimulatory effect on intestinal microbiota. It is highly important that feed compounders acknowledge this finding. Unlike FA, the inhibitory effect of methionine hydroxy analogue on ileal bacteria was linearly dose dependent and significant at inclusion levels above 0.2%, in vitro. Partial replacement of methionine hydroxy analogue by FA, or FA by methionine hydroxy analogue, led to an unpredictable outcome due to the dual effects of FA; e.g., a minor inclusion of added FA changed the inhibitory effect of methionine hydroxy analogue into microbial stimulation by FA. Inhibition of ileal microbiota by methionine hydroxy analogue was detected only in in vitro studies, suggesting that intact methionine hydroxy analogue may not have reached the ileum, in live animals. Therefore

  10. A “false positive” octreoscan in ileal Crohn’s disease

    PubMed Central

    Fernandez, Alberto; Tabuenca, Olga; Peteiro, Angeles

    2008-01-01

    We present a case report of a patient with a suspicious ileal carcinoid tumour. Clinical examination as well as computer tomography (CT) scan suggested a tumour. Octeotride scan showed uptake in the same bowel loop reported as pathological in CT. The patient underwent surgery and biopsy which reported Crohn’s disease (CD). The interest in the case is due to the fact that this is, to the best of our knowledge, the second report of Crohn’s disease as a cause of false positive octeotride scan. Unfortunately, no somatostatin receptors could be found in the sample, so further studies should be performed. PMID:18785291

  11. Probiotics as Antifungals in Mucosal Candidiasis.

    PubMed

    Matsubara, Victor H; Bandara, H M H N; Mayer, Marcia P A; Samaranayake, Lakshman P

    2016-05-01

    Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections.

  12. [Effect of chloditan on the changes of activity of glutathione transferase, glutathione reductase and glutathione content in the adrenal glands and liver in rats].

    PubMed

    Zorich, P A; Tronko, N D; Mikosha, A S

    1994-01-01

    The chloditan (o.p-DDD, mitotane), which causes the destruction of the human and dog adrenal cortex, on the most essential system of xenobiotic metabolism: glutathione-S-transferase--glutathione has been studied. The effect of o,p-DDD on GSH level and activity of glutathione-S-transferase and glutathione reductase which maintain the level of reduced glutathione was analyzed in the adrenal and liver tissue of rats. This species is resistant to adrenocorticolytic action of o,p-DDD. It was shown that feeding of rats weighting 200-240 g with oil solution of o,p-DDD (75 mg daily) for 3 days causes the decrease in activity of glutathione-S-transferase and content of oxidazed glutathione in the adrenals with simultaneous increase of the content of reduced glutathione. The glutathione-S-transferase and glutathione reductase activity in the liver rises under the effect of o,p-DDD, the decrease of the GSH level being observed. The revealed changes may explain the species sensitivity of animals to o,p-DDD.

  13. Subcellular Distribution of Glutathione Precursors in Arabidopsis thaliana

    PubMed Central

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

    2011-01-01

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

  14. 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

  15. Hitting the mucosal road in tolerance induction.

    PubMed

    Wiedermann, Ursula

    2009-01-01

    Within the last decades a dramatic increase in allergic diseases has been recognized in the Westernized societies, leading to the fact that meanwhile 25-30% of the population is afflicted by allergic disorders. Besides a hereditary disposition, other factors, including a reduced microbial contact early in life or changes in nutrition, might also have influenced this epidemiological development. So far the only causative treatment against type-I allergies is specific immunotherapy. In young and monosensitized patients this treatment is highly efficacious, while there are clear limitations in older or multisensitized patients. Allergy research therefore aims at establishing new and more efficacious treatment strategies in prophylactic as well as therapeutic settings. Our research programs focus on the development of novel allergy vaccines based on the induction of mucosal tolerance. In different mouse models of respiratory allergy mucosal treatment with genetically engineered allergen constructs proved to prevent the development of allergic mono- and multisensitivities. The additional use of mucosal adjuvants seems particularly important to improve therapeutic treatment approaches. Recent studies on the inverse relation of certain parasite infections and the development of allergy prompted us to search for selected parasitic molecules with immunosuppressive properties as potential adjuvant systems for novel allergy vaccines. An overview of our recent studies will be given.

  16. Dermoscopic appearance of an amelanotic mucosal melanoma

    PubMed Central

    Blum, Andreas; Beck-Zoul, Ulrike; Held, Laura; Haase, Sylvie

    2016-01-01

    Background Hypomelanotic or amelanotic melanomas are challenging to identify, especially at mucosal sites. The dermoscopic clues to the diagnosis of mucosal melanomas have been reported to be structureless zones with the presence of blue, gray, or white colors. Case A female in her seventies noted a new lesion on the inside of her right labia that first appeared two months prior. Her past medical history was significant for rheumatoid arthritis requiring ongoing treatment with methotrexate for 20 years and adalimumab for 10 years. After no response to two weeks of local treatment for suspected herpes simplex infection, her gynecologist performed a skin biopsy. Based on the histopathological diagnosis of an amelanotic melanoma (Breslow thickness of 1.3 mm) the patient was referred to dermatology for further assessment. Polarized dermoscopy revealed a distinct asymmetric, sharply demarcated homogenous white papule (4 × 5 mm) as well as polymorphous vessels. Conclusion Dermoscopy may aid in the diagnosis of amelanotic mucosal melanomas. Our case revealed a structureless white area and polymorphous vessels. Additional clues to the diagnosis were the advanced age of the patient and the clinical presentation of a new lesion. PMID:27867742

  17. 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.

  18. Age, gender, dentures and oral mucosal disorders.

    PubMed

    MacEntee, M I; Glick, N; Stolar, E

    1998-03-01

    The numbers of participants over 75 years of age in previous studies of oral health have not been sufficient to permit a full investigation of the influence of age on the mouth. In this study a disproportionate stratified random sample of 255 independent elders was selected from a list of urban voters to provide similar numbers of men and women in three age groups. The subjects were interviewed and examined, and nearly half of them had mucosal disorders. There was a significant (P < 0.05) association between mucosal lesions and the use of dentures and tobacco, whereas stomatitis, denture-related hyperplasia and angular cheilitis in particular were associated significantly with men and with the use of defective dentures. Logistic regression revealed that neither age alone nor the quality of dentures predispose to mucosal lesions, but that the odds of finding stomatitis, denture-related hyperplasia and angular cheilitis in particular increased about three-fold in denture-users, and almost doubled in men.

  19. Mucosal perforators from the facial artery.

    PubMed

    Coronel-Banda, Mauricio E; Serra-Renom, Jose M; Lorente, Marian; Larrea-Terán, Wendy P

    2014-07-01

    The cutaneous perforators of the facial artery have been well described, but to our knowledge the oral mucosal perforators have not. We studied 10 facial arteries from 10 hemifaces in 5 cadavers. The arteries were injected with latex, and we studied all perforators that extended from the facial artery and headed directly to the oral mucosa. The diameter and length of the facial artery and its mucosal perforators were measured and compared. We found 52 oral mucosal perforators in the 10 facial arteries injected with latex. Their mean (SD) diameter was 0.5 (0.2) mm and the mean (SD) number/facial artery was 5.2 (1.1). Their mean (SD) length was 16.4 (5.3) mm. Most of those to the cheek were localised between the branching-off points of the inferior and superior labial arteries. The facial artery has perforators to the oral mucosa of the cheek, most of them between the points at which the labial arteries emerge.

  20. Synergistic effects of nicotine on arecoline-induced cytotoxicity in human buccal mucosal fibroblasts.

    PubMed

    Chang, Y C; Hu, C C; Tseng, T H; Tai, K W; Lii, C K; Chou, M Y

    2001-09-01

    Areca quid chewing has been linked to oral submucous fibrosis and oral cancer. Arecoline, a major areca nut alkaloid, is considered to be the most important etiologic factor in the areca nut. In order to elucidate the pathobiological effects of arecoline, cytotoxicity assays, cellular glutathione S-transferase (GST) activity and lipid peroxidation assay were employed to investigate cultured human buccal mucosal fibroblasts. To date, there is a large proportion of areca quid chewers who are also smokers. Furthermore, nicotine, the major product of cigarette smoking, was added to test how it modulated the cytotoxicity of arecoline. At a concentration higher than 50 microg/ml, arecoline was shown to be cytotoxic to human buccal fibroblasts in a dose-dependent manner by the alamar blue dye colorimetric assay (P<0.05). In addition, arecoline significantly decreased GST activity in a dose-dependent manner (P<0.05). At concentrations of 100 microg/ml and 400 microg/ml, arecoline reduced GST activity about 21% and 46%, respectively, during a 24 h incubation period. However, arecoline at any test dose did not increase lipid peroxidation in the present human buccal fibroblast test system. The addition of extracellular nicotine acted synergistically on the arecoline-induced cytotoxicity. Arecoline at a concentration of 50 microg/ml caused about 30% of cell death over the 24 h incubation period. However, 2.5 mM nicotine enhanced the cytotoxic response and caused about 50% of cell death on 50 microg/ml arecoline-induced cytotoxicity. Taken together, arecoline may render human buccal mucosal fibroblasts more vulnerable to other reactive agents in cigarettes via GST reduction. The compounds of tobacco products may act synergistically in the pathogenesis of oral mucosal lesions in areca quid chewers. The data presented here may partly explain why patients who combined the habits of areca quid chewing and cigarette smoking are at greater risk of contracting oral cancer.

  1. Gut permeability and mucosal inflammation: bad, good or context dependent.

    PubMed

    Ahmad, R; Sorrell, M F; Batra, S K; Dhawan, P; Singh, A B

    2017-03-01

    Inflammatory bowel disease (IBD) is a multifactorial disease. A breach in the mucosal barrier, otherwise known as "leaky gut," is alleged to promote mucosal inflammation by intensifying immune activation. However, interaction between the luminal antigen and mucosal immune system is necessary to maintain mucosal homeostasis. Furthermore, manipulations leading to deregulated gut permeability have resulted in susceptibility in mice to colitis as well as to creating adaptive immunity. These findings implicate a complex but dynamic association between mucosal permeability and immune homeostasis; however, they also emphasize that compromised gut permeability alone may not be sufficient to induce colitis. Emerging evidence further supports the role(s) of proteins associated with the mucosal barrier in epithelial injury and repair: manipulations of associated proteins also modified epithelial differentiation, proliferation, and apoptosis. Taken together, the role of gut permeability and proteins associated in regulating mucosal inflammatory diseases appears to be more complex than previously thought. Herein, we review outcomes from recent mouse models where gut permeability was altered by direct and indirect effects of manipulating mucosal barrier-associated proteins, to highlight the significance of mucosal permeability and the non-barrier-related roles of these proteins in regulating chronic mucosal inflammatory conditions.

  2. Glutathione conjugation: atrazine detoxication mechanism in corn.

    PubMed

    Shimabukuro, R H; Swanson, H R; Walsh, W C

    1970-07-01

    Glutathione conjugation (GS-atrazine) of the herbicide, 2-chloro-4-ethylamino-6-isopropylamino-s-triazine (atrazine) is another major detoxication mechanism in leaf tissue of corn (Zea mays, L.). The identification of GS-atrazine is the first example of glutathione conjugation as a biotransformation mechanism of a pesticide in plants. Recovery of atrazine-inhibited photosynthesis was accompanied by a rapid conversion of atrazine to GS-atrazine when the herbicide was introduced directly into leaf tissue. N-De-alkylation pathway is relatively inactive in both roots and shoots. The nonenzymatic detoxication of atrazine to hydroxyatrazine is negligible in leaf tissue. The hydroxylation pathway contributed significantly to the total detoxication of atrazine only when the herbicide was introduced into the plant through the roots. The metabolism of atrazine to GS-atrazine may be the primary factor in the resistance of corn to atrazine.

  3. Effect of glutathione addition in sparkling wine.

    PubMed

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

    2014-09-15

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

  4. Starter Feeding Supplementation Alters Colonic Mucosal Bacterial Communities and Modulates Mucosal Immune Homeostasis in Newborn Lambs

    PubMed Central

    Liu, Junhua; Bian, Gaorui; Sun, Daming; Zhu, Weiyun; Mao, Shengyong

    2017-01-01

    This study aims to investigate the effect of starter feeding supplementation on colonic mucosal bacterial communities and on mucosal immune homeostasis in pre-weaned lambs. We selected eight pairs of 10-day-old lamb twins. One twin was fed breast milk (M, n = 8), while the other was fed breast milk plus starter (M+S, n = 8). The lambs were sacrificed at 56 days age. Colonic content was collected to determine the pH and the concentrations of volatile fatty acids (VFA) and lactate. The colonic mucosa was harvested to characterize the bacterial communities using Illumina MiSeq sequencing and to determine mRNA expression levels of cytokines and toll-like receptors (TLR) using quantitative real-time PCR. The results show that starter feeding decreased luminal pH and increased the concentrations of acetate, propionate, butyrate, total VFA, and lactate in the colon. The principal coordinate analysis (PCA) and analysis of molecular variance show that starter feeding supplementation significantly affected the colonic mucosal bacterial communities with a higher relative abundance of the dominant taxa unclassified S24-7, Oscillibacter, Prevotella, Parabacteroides, Bifidobacterium, Ruminobacter, and Succinivibrio, and a lower proportion of unclassified Ruminococcaceae, RC9_gut_group, Blautia, Phocaeicola, Phascolarctobacterium, unclassified BS11_gut_group, unclassified family_XIII, and Campylobacter in lambs. Meanwhile, starter feeding decreased mRNA expression of TLR4 and cytokines TNF-α and IFN-γ in colonic tissue. Furthermore, the changes in the colonic mucosal mRNA expression of TLR and cytokines were associated with changes in mucosal bacterial composition. These findings may provide new insights into colonic mucosal bacteria and immune homeostasis in developing lambs. PMID:28382025

  5. In vitro evaluation of coating polymers for enteric coating and human ileal targeting.

    PubMed

    Huyghebaert, Nathalie; Vermeire, An; Remon, Jean Paul

    2005-07-14

    Recombinant interleukin-10 producing Lactococcus lactis is an alternative therapy for Crohn's disease. For in vivo interleukin-10 production, thymidine, the essential feed component of these recombinant bacteria should be coadministered. Different coating polymers were evaluated in vitro for enteric properties and targeting suitability to the ileum, the major site of inflammation in Crohn's disease. To guarantee ileal delivery, the polymer must dissolve from pH 6.8 and allow complete release within 40 min. Aqoat AS-HF coated pellets (15%) showed poor enteric properties and thymidine was released below pH 6.8. Eudragit FS30D coated pellets (15%) showed good enteric properties, but no thymidine was released within 40 min at pH 6.8. Eudragit S coated pellets (15%) showed good enteric properties after curing at elevated temperature while no thymidine was released within 40 min at pH 6.8. In another approach to pass the proximal small intestine intact, pellets were coated with 30% Eudragit L30D-55. At pH 6.0, they showed a lag-phase of 20 min. No influence of layer thickness was seen above pH 6.5. Alternatively, pellets were coated with a mixture of Eudragit FS30D/L30D-55 but they showed poor enteric properties and thymidine was released below pH 6.8. In conclusion, none of the tested polymers/mixtures ensured enteric properties and ileal targeting.

  6. Effects of feed additives on the development on the ileal bacterial community of the broiler chicken.

    PubMed

    Lu, J; Hofacre, C; Smith, F; Lee, M D

    2008-05-01

    Intensifying concerns about the use of antimicrobials in meat and poultry production has enhanced interest in the application of prebiotics, probiotics and enzymes to enhance growth and prevent disease in food animals. Growth-promoting antibiotics enhance growth of animals by reducing the load of bacteria in the intestine, by reducing colonization by intestinal pathogens or by enhancing the growth and/or metabolism of beneficial bacteria in the intestine. Recently, molecular ecology, utilizing DNA-sequence heterogeneity of the 16S rRNA gene, has revealed a surprising diversity of uncharacterized bacteria inhabiting this ecosystem. We used this approach to determine the effect of growth-promoting antibiotics on the development and composition of the ileal bacterial community. Pairwise comparisons, correspondence analysis and community diversity indices revealed significant differences among the treatments (bacitracin/virginiamycin or monensin) and controls. Antibiotics reduced the diversity of the ileal bacterial community and induced communities rich in Clostridia throughout the life of the broiler chicken. These results indicate that some bacterial species, such as lactobacilli, were suppressed and also suggest that many intestinal Clostridia may be non-pathogenic. Future studies should focus on characterizing the important bacterial species needed to stabilize the intestinal microbiota and identifying those commensals that stimulate and enhance development of intestinal function.

  7. Robotic Intracorporeal Ileal Conduit Formation: Initial Experience from a Single UK Centre

    PubMed Central

    Bishop, Conrad V.; Adshead, James M.

    2013-01-01

    Objectives. To describe our technique of robotic intracorporeal ileal conduit formation (RICIC) during robotic-assisted radical cystectomy (RARC). To report our initial results of this new procedure. Patients and Methods. Seven male and one female patients underwent RARC with RICIC over a six-month period. Demographic, operative, and outcome data was collected prospectively. Median patient age was 75 years (range 62–78 years). Median followup was 9 months (range 7–14 months). Results. RARC with RICIC was performed successfully in all eight patients. The median total operating time was 360 minutes (range 310–440 minutes) with a median blood loss of 225 mL (range 50–1000 mL). The median length of stay was nine days (range 6–34 days). Four patients (50%) were discharged within seven days. Four patients (50%) experienced one or more complications. This included two Clavien I complications, two Clavien II complications, and two Clavien III complications. Two patients (25%) required transfusion of two units each. To date, there have been no complications associated with the ileal conduit. Conclusion. Whilst being technically challenging, this procedure is safe, feasible, and reproducible. Patients who avoid complication show potential for rapid recovery and early discharge. PMID:24072995

  8. The ultrastructure of bovine ileal follicle-associated epithelial (FAE) cells during the perinatal period.

    PubMed Central

    Asari, M; Kano, Y; Wakui, S; Nishita, T; Matsushita, H; Oshige, H

    1989-01-01

    The ileal follicle-associated epithelial (FAE) cells in bovine fetuses and neonates were examined by light and electron microscopy. In 7-9 months old fetuses (68, 82 and 86 cm CRL) the dome epithelium was usually a little thinner than elsewhere and contained more intra-epithelial leucocytes. FAE cells were already distinguishable by their being more cuboidal and eosinophilic than the other epithelial cells. The cytoplasm of the FAE cells bulged noticeably into the lumen and contained numerous mitochondria and vacuoles. At 18 hours and 21 hours after birth, the dome epithelium was more columnar and eosinophilic than previously and contained more intra-epithelial leucocytes. The FAE cells showed characteristic bulging of large cytoplasmic processes into the lumen, as seen in the previous stage. In the cytoplasm, moderate numbers of mitochondria, numerous vesicles and microtubules could be seen. Frequently degenerated FAE cells could also be found among normal FAE cells in the epithelium. After this stage the cytoplasmic processes almost disappeared but distribution of the other organelles was similar to that seen at the previous stage except that multivesicular bodies were frequently seen in the apical cytoplasm. These histological results suggest that bovine ileal FAE cells are histologically and functionally mature by birth and that at birth they seem to be able to react against the penetration of pathogenic substances from the extrauterine environment. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:2606783

  9. Functional Assessment of the Hautmann Ileal Neobladder with Chimney Modification Using Uroflowmetry and a Questionnaire

    PubMed Central

    Jung, Ha Bum; Choi, Don Kyoung; Cho, Sung Tae; Kim, Ki Kyung

    2016-01-01

    Urinary diversion reconstruction is essential after radical cystectomy and neobladder reconstruction is accepted as a fine option. This study included 51 patients, who underwent radical cystectomy with orthotopic neobladder reconstruction by a Hautmann ileal neobladder with chimney modification from 2006 to 2014. Functional outcomes were evaluated using a questionnaire and uroflowmetry. Perioperative complications were analyzed retrospectively. The mean follow-up period was 36.1 months. Eighty-six percent of patients voided without clean intermittent catheterization (CIC) assistance. CIC was used 1-2x per day or every time they voided in 8% and 6% of patients, respectively, and 71% of patients were continent. The percentages of patients who used 1, 2, 3-4, and ≥5 pads per day were 15%, 6%, 2%, and 6%, respectively. Daytime and nighttime continence were achieved in 86% and 69% of patients, respectively. Daily mucus leakage was reported in 69% of patients. The mean maximum neobladder capacity, voided volume, postvoid residual volume, and maximum flow rate were 413.2 mL, 370.6 mL, 43.7 mL, and 20.8 mL/s, respectively. Eighteen early and 5 late complications developed in 13 and 5 patients, respectively. Reoperations were needed in 7 patients. The Hautmann ileal neobladder with chimney modification provided satisfactory results regarding functional outcomes. PMID:28025648

  10. Ileal interposition attenuates the satiety responses evoked by cholecystokinin-8 and -33.

    PubMed

    Metcalf, Shannon A; Washington, Martha C; Brown, Thelma A L; Williams, Carol S; Strader, April D; Sayegh, Ayman I

    2011-06-01

    One of the possible mechanisms by which the weight-reducing surgical procedure ileal interposition (II) works is by increasing circulating levels of lower gut peptides that reduce food intake, such as glucagon like peptide-1 and peptide YY. However, since this surgery involves both lower and upper gut segments, we tested the hypothesis that II alters the satiety responses evoked by the classic upper gut peptide cholecystokinin (CCK). To test this hypothesis, we determined meal size (MS), intermeal interval (IMI) and satiety ratio (SR) evoked by CCK-8 and -33 (0, 1, 3, 5nmol/kg, i.p.) in two groups of rats, II and sham-operated. CCK-8 and -33 reduced MS more in the sham group than in the II group; CCK-33 prolonged IMI in the sham group and increased SR in both groups. Reduction of cumulative food intake by CCK-8 in II rats was blocked by devazepide, a CCK(1) receptor antagonist. In addition, as previously reported, we found that II resulted in a slight reduction in body weight compared to sham-operated rats. Based on these observations, we conclude that ileal interposition attenuates the satiety responses of CCK. Therefore, it is unlikely that this peptide plays a significant role in reduction of body weight by this surgery.

  11. Buccal mucosal graft in reconstructive urology: uses beyond urethral stricture.

    PubMed

    Pandey, Abhishek; Dican, Razvan; Beier, Jörn; Keller, Hansjörg

    2014-07-01

    The use of buccal mucosal grafts for the reconstruction of urethral strictures is an established procedure. Because of its robustness, the buccal mucosal graft could also potentially provide an alternative for other indications in reconstructive urology. We report here six consecutive patients who received a buccal mucosal graft for ureteral strictures, glans reconstruction and stoma stenosis. The follow up for all patients ranged from 26 to 50 months. The buccal mucosal graft showed excellent functional results for the ureteral strictures and stenosis from ureterocutaneostomy. For glans reconstructions, the buccal mucosal grafts delivered excellent cosmetic and functional results without causing meatal stenosis. We conclude the buccal mucosal graft can be used in reconstructive surgery beyond the reconstruction of urethral strictures.

  12. Enhancement of gastric mucosal blood flow with sulglycotide.

    PubMed

    Guslandi, M; Sorghi, M; Tittobello, A

    1994-01-01

    Twelve patients with dyspepsia whose gastric abnormalities ranged from diffuse reddening of the mucosa to multiple erosions were treated for 4 weeks with oral sulglycotide, a sulphated glycopeptide with known gastroprotective and ulcer-healing properties. Before and after treatment, gastric mucosal blood flow was assessed by means of laser Doppler flowmetry. A significant (P < 0.01) increase in mucosal perfusion was observed after sulglycotide treatment, suggesting that enhancement of mucosal blood flow may contribute to the therapeutic properties of the drug.

  13. Evidence for a common mucosal immune system in the pig.

    PubMed

    Wilson, Heather L; Obradovic, Milan R

    2015-07-01

    The majority of lymphocytes activated at mucosal sites receive instructions to home back to the local mucosa, but a portion also seed distal mucosa sites. By seeding distal sites with antigen-specific effector or memory lymphocytes, the foundation is laid for the animal's mucosal immune system to respond with a secondary response should to this antigen be encountered at this site in the future. The common mucosal immune system has been studied quite extensively in rodent models but less so in large animal models such as the pig. Reasons for this paucity of reported induction of the common mucosal immune system in this species may be that distal mucosal sites were examined but no induction was observed and therefore it was not reported. However, we suspect that the majority of investigators simply did not sample distal mucosal sites and therefore there is little evidence of immune response induction in the literature. It is our hope that more pig immunologists and infectious disease experts who perform mucosal immunizations or inoculations on pigs will sample distal mucosal sites and report their findings, whether results are positive or negative. In this review, we highlight papers that show that immunization/inoculation using one route triggers mucosal immune system induction locally, systemically, and within at least one distal mucosal site. Only by understanding whether immunizations at one site triggers immunity throughout the common mucosal immune system can we rationally develop vaccines for the pig, and through these works we can gather evidence about the mucosal immune system that may be extrapolated to other livestock species or humans.

  14. 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

  15. 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.

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

    PubMed Central

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

    2014-01-01

    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

  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. 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...

  19. 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...

  20. Pouchitis-associated iritis (uveitis) following total proctocolectomy and ileal pouch-to-anal anastomosis in ulcerative colitis.

    PubMed

    Freeman, H J

    2001-02-01

    A 26-year-old woman with ulcerative colitis treated with a proctocolectomy and ileal pouch-to-anal anastomosis developed an erosive and ulcerative pouchitis. Although no ophthalmological manifestations were present before the staged surgical procedures, iritis developed after appearance of the pouchitis. Both conditions subsequently resolved with oral corticosteroids and metronidazole.

  1. Protective effect of Bu-Zhong-Yi-Qi decoction, the water extract of Chinese traditional herbal medicine, on 5-fluorouracil-induced intestinal mucositis in mice.

    PubMed

    Gou, H; Gu, L Y; Shang, B Z; Xiong, Y; Wang, C

    2016-12-01

    Intestinal mucositis is a serious toxic side effect of 5-fluorouracil (5-FU) treatment. Bu-Zhong-Yi-Qi decoction (BZYQD), a water extract of Chinese traditional herbal medicine, is widely used in chemotherapy in Asia as an alternative treatment to reduce the side effects of chemotherapy. However, the mechanism is unknown. To evaluate its mechanism, we investigated the effect of BZYQD on 5-FU-induced intestinal mucositis in mice, especially with regard to apoptosis in the intestinal mucosal epithelia. In the present study, mice were divided into three groups: control, 5-FU, and 5-FU + BZYQD. Mice in the 5-FU and 5-FU + BZYQD groups were administered 5-FU (100 mg/kg/day, intraperitoneally) for 6 days, and the mice in the latter group were given BZYQD (8 g/kg/day, intragastrically) beginning 4 days before 5-FU and continuing until the termination of the experiment. Loss in body weight and diarrhea during the 5-FU treatment were significantly attenuated by administration of BZYQD. The morphological signs of intestinal damage, including shortened villi height, crypt destruction, apoptosis, and necrosis, in intestinal mucosal epithelia were also reversed, accompanied by reduced neutrophil infiltration, nitrite levels, and inflammatory factors (tumor necrosis factor α and interleukin 1β) and increased levels of reduced glutathione. These results suggest that BZYQD inhibits 5-FU-induced intestinal mucositis, and this effect may be due to the reduction in apoptosis and necrosis in intestinal mucosal epithelia via the suppression of inflammatory cytokine upregulation. In conclusion, inhibiting cytokine-mediated apoptosis or necrosis can be the molecular mechanism by which BZYQD reduces the gastrointestinal side effects of cancer chemotherapy.

  2. Gut mucosal immunostimulation by lactic acid bacteria.

    PubMed

    Vitiñi, E; Alvarez, S; Medina, M; Medici, M; de Budeguer, M V; Perdigón, G

    2000-12-01

    The beneficial properties of lactic acid bacteria (LAB) on human health have been frequently demonstrated. The interaction of LAB with the lymphoid cells associated to the gut to activate the mucosal immune system and the mechanisms by which they can exert an adjuvant effect is still unclear, as well as if this property is common for all the LAB. We studied the influence of the oral administration of different geneous of LAB such as Lactobacillus casei, L. acidophilus, L. rhamnosus, L. delbrueckii subsp. bulgaricus, L. plantarum, Lactococcus lactis and Streptococcus thermophilus. We determined if the LAB assayed were able to stimulate the specific, the non-specific immune response (inflammatory response), or both. We demonstrated that all the bacteria assayed were able to increase the number of IgA producing cells associated to the lamina propria of small intestine. This effect was dose dependent. The increase in IgA+ producing cells was not always correlated with an increase in the CD4+ T cell number, indicating that some LAB assayed only induced clonal expansion of B cells triggered to produce IgA. Most of them, induced an increase in the number of cells involved in the inflammatory immune response. CD8+ T cell were diminished or not affected, with exception of L. plantarum that induced an increase at low dose. This fact would mean that LAB are unable to induce cytotoxicity mechanisms. We demonstrated the importance in the selection of LAB to be used as gut mucosal adjuvant. The different behaviours observed among them on the gut mucosal immune response, specially those that induce inflammatory immune response, show that not all the LAB can be used as oral adjuvant and that the beneficial effect of them can not generalized to genous or specie. The immunoadjuvant capacity would be a property of the strain assayed.

  3. Glycerol monolaurate prevents mucosal SIV transmission

    PubMed Central

    Li, Qingsheng; Estes, Jacob D.; Schlievert, Patrick M.; Duan, Lijie; Brosnahan, Amanda J.; Southern, Peter J.; Reilly, Cavan S.; Peterson, Marnie L.; Schultz-Darken, Nancy; Brunner, Kevin G.; Nephew, Karla R.; Pambuccian, Stefan; Lifson, Jeffrey D.; Carlis, John V.; Haase, Ashley T.

    2009-01-01

    While there has been great progress in treating HIV-1 infection1, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission2–4. Nonetheless, studies of vaginal transmission in the SIV-rhesus macaque model point to opportunities in the earliest stages of infection where a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry5, 6. Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3α, plasmacytoid dendritic cells and CCR5+cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruit CD4+T cells to fuel this obligate expansion. We then show that glycerol monolaurate, a widely used antimicrobial compound 7 with inhibitory activity against production of MIP-3α and other proinflammatory cytokines8, can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This novel approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for development of effective interventions to block HIV-1 mucosal transmission. PMID:19262509

  4. 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

  5. Glycerol monolaurate prevents mucosal SIV transmission.

    PubMed

    Li, Qingsheng; Estes, Jacob D; Schlievert, Patrick M; Duan, Lijie; Brosnahan, Amanda J; Southern, Peter J; Reilly, Cavan S; Peterson, Marnie L; Schultz-Darken, Nancy; Brunner, Kevin G; Nephew, Karla R; Pambuccian, Stefan; Lifson, Jeffrey D; Carlis, John V; Haase, Ashley T

    2009-04-23

    Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission. Nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (SIV)-rhesus macaque (Macacca mulatta) model point to opportunities at the earliest stages of infection in which a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry. Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3alpha (also known as CCL20), plasmacytoid dendritic cells and CCR5(+ )cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruits CD4(+) T cells to fuel this obligate expansion. We then show that glycerol monolaurate-a widely used antimicrobial compound with inhibitory activity against the production of MIP-3alpha and other proinflammatory cytokines-can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo it can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This new approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for the development of effective interventions to block HIV-1 mucosal transmission.

  6. Vitamin D and mucosal immune function

    PubMed Central

    Sun, Jun

    2010-01-01

    Purpose of review Significant advances have been made in the characterization of Vitamin D and the Vitamin D receptor (VDR) in immune function. The studies of signaling pathways involved in the response to infection and inflammation have led to a more detailed understanding of the cellular response to Vitamin D through VDR. This review summarizes recent progress in understanding how Vitamin D contributes to mucosal immune function, particularly in relation to the molecular mechanisms by which Vitamin D and VDR influence mucosal immunity, bacterial infection, and inflammation. Recent findings Recently, it was shown that Vitamin D modulates the T cell antigen receptor, further demonstrating that Vitamin D has a nonclassical role in immunoregulation. The anti-inflammation and anti-infection functions for Vitamin D are newly identified and highly significant activities. Vitamin D/VDR have multiple critical functions in regulating the response to intestinal homeostasis, tight junctions, pathogen invasion, commensal bacterial colonization, antimicrobe peptide secretion, and mucosal defense. Interestingly, microorganisms modulate the VDR signaling pathway. Summary Vitamin D is known as a key player in calcium homeostasis and electrolyte and blood pressure regulation. Recently, important progress has been made in understanding how the noncanonical activities of Vitamin D influence the pathogenesis and prevention of human disease. Vitamin D and VDR are directly involved in T cell antigen receptor signaling. The involvement of Vitamin D/VDR in anti-inflammation and anti-infection represents a newly identified and highly significant activity for VDR. Studies have indicated that the dysregulation of VDR may lead to exaggerated inflammatory responses, raising the possibility that defects in Vitamin D and VDR signaling transduction may be linked to bacterial infection and chronic inflammation. Further characterization of Vitamin D/VDR will help elucidate the pathogenesis of

  7. Inhibition of glutathione conjugation in the rat in vivo by analogues of glutathione conjugates.

    PubMed

    Ouwerkerk-Mahadevan, S; Mulder, G J

    1998-04-24

    Glutathione (GSH) conjugation plays an important role in (de-)toxification of its substrates in vivo. We have developed inhibitors of GSH conjugation that are active in the rat in vivo which are derived from the structure of GSH conjugates: they contain a backbone of gamma-L-Glu-D-2-aminoadipic acid that is virtually isosteric with the gamma-L-Glu-L-Cys-Gly structure of GSH. In addition, a hydrophobic alkyl group is attached such that it may interact with the H-site of the enzyme. Finally, the carboxyl groups were esterified with alcohols of varying chain length. The results show that all these compounds preferentially inhibit alpha-GST's 1-1 and 2-2, have less effect on mu isoenzymes 3-3 and 4-4, and finally, have little effect on rat theta (G.J. Mulder, S. Ouwerkerk-Mahadevan, Modulation of glutathione conjugation in vivo: How to decrease glutathione conjugation in vivo or in intact cellular systems in vitro, Chem. Biol. Interact. 105 (1997) 17-34) and pi (S. Ouwerkerk-Mahadevan, J.H. van Boom, M.C. Dreef-Tromp, J.H.T.M. Ploemen, D.J. Meyer, G.J. Mulder, Glutathione analogues as novel inhibitors of rat and human glutathione S-transferase isoenzymes, as well as of glutathione conjugation in isolated rat hepatocytes and the rat in vivo, Bioche. J., 308 (1995) 283-290). Several of the compounds inhibit the GSH conjugation of bromsulfophthalein and (S)-2-bromisovalerylurea in hepatocytes, in the situ recirculating rat liver perfusion and in the rat in vivo (after i.v. administration). The most effective compound contains a 2-heptylamine group linked as an amide to the 1-carboxyl group of the aminoadipic acid moiety at the H-site, and an ethyl ester at the 5-carboxylic acid group of aminoadipic acid.

  8. Oral lichen planus and lichenoid mucositis.

    PubMed

    De Rossi, Scott S; Ciarrocca, Katharine

    2014-04-01

    Oral lichen planus (OLP) is commonly found in middle-aged women. Although the cause is unknown, research points to several complex immunologic events and cells that are responsible for the inflammatory destruction and chronicity of these lesions. Biopsy for histologic diagnosis is recommended. The mainstay of treatment remains topical corticosteroids; however, newer therapies such as immunomodulating agents are available for recalcitrant lesions. In cases of lichenoid mucositis or reactions, treatment should be directed at identifying and removing the presumed cause. Given the apparent risk of squamous cell carcinoma in these patients, frequent follow-up and repeat biopsy are vital.

  9. 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

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

    PubMed

    Adeola, O; Walk, C L

    2013-08-01

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

  11. The development of mucosal vaccines for both mucosal and systemic immune induction and the roles played by adjuvants

    PubMed Central

    2017-01-01

    Vaccination is the most successful immunological practice that improves the quality of human life and health. Vaccine materials include antigens of pathogens and adjuvants potentiating the effectiveness of vaccination. Vaccines are categorized using various criteria, including the vaccination material used and the method of administration. Traditionally, vaccines have been injected via needles. However, given that most pathogens first infect mucosal surfaces, there is increasing interest in the establishment of protective mucosal immunity, achieved by vaccination via mucosal routes. This review summarizes recent developments in mucosal vaccines and their associated adjuvants. PMID:28168169

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

    PubMed Central

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

    2016-01-01

    Most of amino acid (AA) digestibility values for feed ingredients are obtained using pigs cannulated in the distal ileum. The ileal-cannulated pig model uses pigs older than six weeks due to difficulties related to implanting the T-cannula in distal ileum of younger pigs and complications during the post-surgical recovery. However, to properly formulate the diet of weaned pigs, the nutritive value of feed ingredients should be determined with younger pigs. Thus, 25 weaned pigs were used to determine the apparent total tract digestibility (ATTD) of nutrients, energy, and apparent ileal digestibility (AID) and standardized ileal digestibility (SID) ileal AA digestibility of broken rice (BR), with or without multicarbohydrase (MC) and phytase (Phy) supplementation. Piglets were weaned at 23 d of age and individually housed in digestibility cages until 45 d of age. The trial consisted of 7 d of adaptation to the experimental diets and 3 d of excreta (feces and urine) collection. Ileal digesta was collected at slaughter (about 6 weeks of age). A completely randomized experimental design was used to determine the effects of MC and Phy. Reference diets (RD, 5% casein) was replaced by 30% of BR with or without MC, Phy, or MC+Phy. The RD was used to quantify endogenous AA losses. BR with Phy supplied had increased the ATTD of dry matter (p<0.05) and SID of histidine (p = 0.05), arginine, leucine, lysine, valine, alanine, and proline (p<0.05). BR with MC had been increased digestible energy and protein and SID for histidine (p<0.05). There was no interaction between Phy and MC on the BR nutrient digestibilities. Standardized amino acid digestibilities of BR, without enzymes, were lower than those values reported in the literature. The MC and Phy improved the digestibility of some nutrients and energy of BR in post-weaned piglet diets. PMID:27004821

  13. 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.

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

    PubMed Central

    2014-01-01

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

  15. Catabolism of Glutathione Conjugates in Arabidopsis thaliana

    PubMed Central

    Brazier-Hicks, Melissa; Evans, Kathryn M.; Cunningham, Oliver D.; Hodgson, David R. W.; Steel, Patrick G.; Edwards, Robert

    2008-01-01

    The safener fenclorim (4,6-dichloro-2-phenylpyrimidine) increases tolerance to chloroacetanilide herbicides in rice by enhancing the expression of detoxifying glutathione S-transferases (GSTs). Fenclorim also enhances GSTs in Arabidopsis thaliana, and while investigating the functional significance of this induction in suspension cultures, we determined that these enzymes glutathionylated the safener. The resulting S-(fenclorim)-glutathione conjugate was sequentially processed to S-(fenclorim)-γ-glutamyl-cysteine and S-(fenclorim)-cysteine (FC), the latter accumulating in both the cells and the medium. FC was then either catabolized to 4-chloro-6-(methylthio)-phenylpyrimidine (CMTP) or N-acylated with malonic acid. These cysteine derivatives had distinct fates, with the enzymes responsible for their formation being induced by fenclorim and FC. Fenclorim-N-malonylcysteine was formed from FC by the action of a malonyl-CoA-dependent N-malonyltransferase. A small proportion of the fenclorim-N-malonylcysteine then underwent decarboxylation to yield a putative S-fenclorim-N-acetylcysteine intermediate, which underwent a second round of GST-mediated S-glutathionylation and subsequent proteolytic processing. The formation of CMTP was catalyzed by the concerted action of a cysteine conjugate β-lyase and an S-methyltransferase, with the two activities being coordinately regulated. Although the fenclorim conjugates tested showed little GST-inducing activity in Arabidopsis, the formation of CMTP resulted in metabolic reactivation, with the product showing good enhancing activity. In addition, CMTP induced GSTs and herbicide-safening activity in rice. The bioactivated CMTP was in turn glutathione-conjugated and processed to a malonyl cysteine derivative. These results reveal the surprisingly complex set of competing catabolic reactions acting on xenobiotics entering the S-glutathionylation pathway in plants, which can result in both detoxification and bioactivation. PMID

  16. Blood glutathione status following distance running.

    PubMed

    Dufaux, B; Heine, O; Kothe, A; Prinz, U; Rost, R

    1997-02-01

    In 12 moderately trained subjects reduced glutathione (GSH) and oxidized glutathione (GSSG) as well as thiobarbituric acid reactive substances (TBARS) were measured in the blood before and during the first two hours and first two days after a 2.5-h run. The participants covered between 19 and 26 km (20.8 +/- 2.5 km, mean +/- SD). The running speed was between 53 and 82% of the speed at which blood lactate concentration reached 4 mmol/L lactate (67.9 +/- 8.2%, mean +/- SD) assessed during a previously performed treadmill test. Blood samples were collected 1 h before, immediately before, immediately after, 1 and 2 h after, as well as 1 and 2 days after the run. Immediately after exercise GSH was significantly decreased (p < 0.01) and GSSG significantly increased (p < 0.01). In all subjects the ratio of GSH to GSSG showed a marked decline to 18 +/- 4% (mean +/- SD) of the pre-exercise values (p < 0.01). One hour later the mean GSH and GSSG values returned to baseline. However, there were considerable inter-individual differences. In some subjects the GSH/ GSSG ratio overshot the pre-exercise levels, in others the ratio remained low even two hours after exercise. Compared with the pre-exercise values TBARS concentrations did not change significantly at any time point after exercise. The findings suggest that after prolonged exercise in moderately trained subjects a critical shift in the blood glutathione redox status may be reached. The changes observed were generally short-lived, the duration of which may have depended on the relative importance of reactive oxygen species generation by the capillary endothelial cells and neutrophil and eosinophil granulocytes after the end of exercise.

  17. Iron medication-induced gastric mucosal injury.

    PubMed

    Zhang, Xuchen; Ouyang, Jie; Wieczorek, Rosemary; DeSoto, Fidelina

    2009-01-01

    Severe gastrointestinal erosion, ulcer, necrosis and strictures after an acute iron overdose are well described. However, gastric mucosal injury in patients receiving therapeutic iron has received only scant recognition despite its wide use. We report a case of iron medication-induced gastric mucosal injury in a 76-year-old male who presented with iron deficiency anemia and had been taking ferrous sulfate tablet for 4 years. Esophagogastroduodenoscopy (EGD) revealed a pale, villous appearing flat lesion along the lesser curvature of gastric body. Histopathologic examination of EGD biopsies of the flat lesion showed brown crystalline materials deposited in the lamina propria of gastric mucosa, which was accompanied with fibrosis, chronic inflammation, and foreign body reaction. The crystalline materials were covered and admixed with gastric epithelium. Prussian blue iron stain confirmed that the brown crystalline materials were iron. The iron and hemosiderin accumulation was also seen in cytoplasm of epithelial cells and lumen of fundic gastric glands. The recognition and reporting by pathologists of iron-induced changes in EGD biopsies will alert clinicians to this underrecognized but easily correctable complication by alternative forms of iron therapy, such as liquid preparation.

  18. Dexmedetomidine decreases the oral mucosal blood flow.

    PubMed

    Kawaai, Hiroyoshi; Yoshida, Kenji; Tanaka, Eri; Togami, Kohei; Tada, Hitoshi; Ganzberg, Steven; Yamazaki, Shinya

    2013-12-01

    There is an abundance of blood vessels in the oral cavity, and intraoperative bleeding can disrupt operations. There have been some interesting reports about constriction of vessels in the oral cavity, one of which reported that gingival blood flow in cats is controlled by sympathetic α-adrenergic fibres that are involved with vasoconstriction. Dexmedetomidine is a sedative and analgesic agent that acts through the α-2 adrenoceptor, and is expected to have a vasoconstrictive action in the oral cavity. We have focused on the relation between the effects of α-adrenoceptors by dexmedetomidine and vasoconstriction in oral tissues, and assessed the oral mucosal blood flow during sedation with dexmedetomidine. The subjects comprised 13 healthy male volunteers, sedated with dexmedetomidine in a loading dose of 6 μg/kg/h for 10 min and a continuous infusion of 0.7 μg/kg/h for 32 min. The mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR), and palatal mucosal blood flow (PMBF) were measured at 0, 5, 10, 12, 22, and 32 min after the start of the infusion. The HR, CO, and PBMF decreased significantly during the infusion even though there were no differences in the SV. The SVR increased significantly but the PMBF decreased significantly. In conclusion, PMBF was reduced by the mediating effect of dexmedetomidine on α-2 adrenoceptors.

  19. Th17 cells and Mucosal Host Defense

    PubMed Central

    Aujla, Shean J.; Dubin, Patricia J.; Kolls, Jay K.

    2008-01-01

    Th17 cells are a new lineage of T-cells that are controlled by the transcription factor RORγt and develop independent of GATA-3, T-bet, Stat 4 and Stat 6. Novel effector molecules produced by these cells include IL-17A, IL-17F, IL-22, and IL-26. IL-17RA binds IL-17A and IL-17F and is critical for host defense against extracellular planktonic bacteria by regulating chemokine gradients for neutrophil emigration into infected tissue sites as well as host granulopoiesis. Moreover IL-17 and IL-22 regulate the production of antimicrobial proteins in mucosal epithelium. Although TGF-β1 and IL-6 have been shown to be critical for development of Th17 cells from naïve precursors, IL-23 is also important in regulating IL-17 release in mucosal tissues in response to infectious stimuli. Compared to Th1 cells, IL-23 and IL-17 show limited roles in controlling host defense against primary infections with intracellular bacteria such as Mycobacterium tuberculosis suggesting a predominate role of the Th17 lineage in host defense against extracellular pathogens. However in the setting of chronic biofilm infections, as that occurs with Cystic Fibrosis or bronchetctasis, Th17 cells may be key contributors of tissue injury. PMID:18054248

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

    PubMed

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

    2008-06-01

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

  1. MEMBRANE MODIFICATIONS IN THE APICAL ENDOCYTIC COMPLEX OF ILEAL EPITHELIAL CELLS

    PubMed Central

    Wissig, S. L.; Graney, D. O.

    1968-01-01

    Ileal lining cells of the suckling rat possess an "apical endocytic complex" capable of sequestering intact protein from the intestinal lumen. The complex consists of a network of invaginations of the apical plasma membrane, a number of subjacent small vesicles, and a giant supranuclear vacuole. The first two components initially incorporate material from the intestinal lumen and then transfer it to the giant vacuole where it is stored. Their limiting membrane displays striking structural modifications when viewed in various planes of section. Its lumenal dense leaflet appears discontinuous and consists of an ordered array of minute discrete plaques. A dense particle approximately 70 A in diameter is centered over each plaque. The particles are arranged in a two-dimensional square lattice with center-to-center spacing of approximately 120 A. PMID:4177378

  2. Mucoadhesion of hydroxypropylmethacrylate nanoparticles to rat intestinal ileal segments in vitro.

    PubMed

    Pimienta, C; Lenaerts, V; Cadieux, C; Raymond, P; Juhasz, J; Simard, M A; Jolicoeur, C

    1990-01-01

    The purpose of this study was to evaluate the adhesion of HPMA nanoparticles to mucus using a perfused rat ileum test system. Radiolabeled nanoparticles were prepared and deposited onto rat ileal segments in vitro. The segments were perfused and the perfusate was collected in fractions and assayed for radioactivity. Between 10 and 50% of the radioactivity was eliminated over the first 120-sec perfusion, whereas the remaining activity was firmly attached to the ileum. Among the variables tested, the time interval between nanoparticle deposition and perfusion played the major role, indicating that the mucus-nanoparticle interaction is likely to result from the diffusion of polymers into the mucus and of mucin into the polymeric matrix.

  3. Orthotopic ileal neobladder in female patients after radical cystectomy: 2-year experience.

    PubMed

    Cancrini, A; De Carli, P; Fattahi, H; Pompeo, V; Cantiani, R; Von Heland, M

    1995-03-01

    We describe a surgical technique to conserve urinary continence in 7 women who underwent radical cystectomy with construction of an orthotopic ileal neobladder for infiltrating bladder carcinoma. The selection of the patients and the surgical procedure to preserve the anatomical and functional integrity of the female urethra are described. Followup ranged from 7 to 28 months. There were no postoperative deaths or serious clinical complications. The urinary continence rate was 100% during the day and 71% at night with micturition at regular 3-hour intervals. The vesical capacity varied from 250 to 400 cc and pressure at maximum capacity from 10 to 25 cm. water. Urinary flow was satisfactory and the urethral pressure profile showed a normal sphincteric mechanism at rest. Two patients died of metastases at 14 and 8 months postoperatively, and 5 are alive and disease-free. We believe that these results confirm the possibility of obtaining micturition in women via the urethra following radical cystectomy.

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

    PubMed Central

    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

  5. 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).

  6. Enhanced ileal absorption of a hydrophilic macromolecule, pentosan polysulfate sodium (PPS).

    PubMed

    Dong, Liang; Yum, Alicia; Nguyen, Joe; Wong, Pat

    2004-01-01

    An in situ gelling, bioadhesive liquid formulation was developed to enhance the bioavailbility (BA) of a polysaccharide, pentosan polysulfate sodium (PPS). The formulation was tested to determine its bioavailability enhancement in a non-flush/non-ligated rat ileal model. A potent synergistic effect was found with a gelling agent Cremophor and a permeation enhancer sodium salicylate. The absolute bioavailabilities were 1.9%, 4.6%, 6.3% and 46.4%, respectively, for the PPS solution in saline, sodium salicylate/PPS, Cremophor/PPS and Cremophor/sodium salicylate/PPS. Therefore, we successfully demonstrated the approach of utilizing an in situ gelling/bioadhesive liquid carrier to enhancing the bioavailability of a hydrophilic macromolecule at the distal small intestine.

  7. 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.

  8. Computed tomography-guided endoscopic needle knife therapy for ileal pouch sinus.

    PubMed

    Nyabanga, Custon T; Veniero, Joseph; Shen, Bo

    2016-11-01

    Ileal pouch-anal anastomosis surgery can be complicated by anastomotic leaks, leading to the formation of abscess and chronic sinus that have been routinely managed by a surgical approach. We developed the endoscopic needle knife sinusotomy (NKSi) technique, which has become a valid alternative. The basic principle of endoscopic NKSi is dissection and drainage of the sinus through its orifice internally into the lumen of pouch body. The success of NKSi requires an access to the sinus from the pouch side. One of the most challenging situations for NKSi is a closed orifice of the sinus, which leaves an isolated chronic abscess cavity. Here we report a case of complicated presacral sinus with a closed orifice that was not amenable to NKSi, necessitating a CT-guided guide wire placement and subsequent NKSi.

  9. Minimally invasive treatment of oral ranula with a mucosal tunnel.

    PubMed

    Jia, T; Xing, L; Zhu, F; Jin, X; Liu, L; Tao, J; Chen, Y; Gao, Z; Zhang, H

    2015-02-01

    We have developed a new method for minimally-invasive treatment of uncomplicated oral ranulas using a mucosal tunnel, and we report the clinical outcome. We constructed a mucosal tunnel for each of 35 patients who presented with an oral ranula, by making 2 parallel incisions across the top of the protruding ranula 2-3mm apart, and dissected the soft tissue along the incisions to its wall. The fluid was removed and the cavity irrigated with normal saline. The wall of the ranula was not treated. The first mucosal tunnel was made by suturing the base of the mucosal strip to the deepest part of the wall of the ranula. The mucosal base of the tunnel and the deepest part of the base of the ranula were fixed with absorbable sutures. The two external edges of the incisions were sutured together to form the second mucosal tunnel, and apposing sutures were inserted between the two parallel incisions to form two natural mucosal tunnels. The duration of follow-up ranged from 1 to 5 years. One patient was lost to follow-up and 34 patients were cured. Outcomes were satisfactory without relapse during the follow-up period and the patients were satisfied with the outcome. The mucosal tunnel is a safe, effective, simple, and minimally-invasive treatment for oral ranula.

  10. Induction of mucosal immunity through systemic immunization: Phantom or reality?

    PubMed Central

    Su, Fei; Patel, Girishchandra B.; Hu, Songhua; Chen, Wangxue

    2016-01-01

    ABSTRACT Generation of protective immunity at mucosal surfaces can greatly assist the host defense against pathogens which either cause disease at the mucosal epithelial barriers or enter the host through these surfaces. Although mucosal routes of immunization, such as intranasal and oral, are being intensely explored and appear promising for eliciting protective mucosal immunity in mammals, their application in clinical practice has been limited due to technical and safety related challenges. Most of the currently approved human vaccines are administered via systemic (such as intramuscular and subcutaneous) routes. Whereas these routes are acknowledged as being capable to elicit antigen-specific systemic humoral and cell-mediated immune responses, they are generally perceived as incapable of generating IgA responses or protective mucosal immunity. Nevertheless, currently licensed systemic vaccines do provide effective protection against mucosal pathogens such as influenza viruses and Streptococcus pneumoniae. However, whether systemic immunization induces protective mucosal immunity remains a controversial topic. Here we reviewed the current literature and discussed the potential of systemic routes of immunization for the induction of mucosal immunity. PMID:26752023

  11. OCT visualization of acute radiation mucositis: pilot study

    NASA Astrophysics Data System (ADS)

    Gladkova, Natalia; Maslennikova, Anna; Terentieva, Anna; Fomina, Yulia; Khomutinnikova, Nina; Balalaeva, Irina; Vyseltseva, Yulia; Larin, Roman; Kornoukhova, Natalia; Shakhov, Andrey; Shakhova, Natalia; Gelikonov, Grigory; Kamensky, Vladislav; Feldchtein, Felix

    2005-08-01

    We present pilot results in optical coherence tomography (OCT) visualization of normal mucosa radiation damage. 15 patients undergoing radiation treatment of head and neck cancer were enrolled. OCT was used to monitor the mucositis development during and after treatment. OCT can see stages of radiation mucositis development, including hidden ones, before any clinical manifestations.

  12. Histopathological findings of extra-ileal manifestations at initial diagnosis of Crohn's disease-related ileitis.

    PubMed

    Brown, Ian S; Miller, Gregory C; Bettington, Mark L; Rosty, Christophe

    2016-11-01

    Crohn's disease is a chronic inflammatory disorder that can affect any part of the gastrointestinal tract. Our objective was to review the histological findings in index biopsies from the terminal ileum and other gastro-intestinal tract sites of Crohn's disease patients prior any treatment and to compare them with the findings from patients with non-specific ileitis. A total of 111 consecutive Crohn's disease cases (55 females, median age 27 years) with extra-ileal biopsies were retrospectively selected. Upper gastrointestinal inflammatory changes were found in 68 % of gastric biopsies, 60 % of oesophageal biopsies and 43 % of duodenal biopsies with no significant difference in frequency between paediatric and adult cases. Crohn's colitis was more common in paediatric cases than adult cases (85 % versus 57 %). Granuloma in at least one extra-ileal site was observed in 40 %, more frequently in paediatric cases than in adults (78 vs 27 %). Compared with Crohn's disease cases, the group of 151 non-specific ileitis cases (75 females, median age 52 years) were more likely to have normal upper and lower gastrointestinal biopsies and to show less frequent crypt architectural changes in the terminal ileum. In summary, Crohn's disease ileitis is often associated with inflammation elsewhere in the gastrointestinal tract while non-specific ileitis was infrequently associated with inflammation elsewhere for both paediatric and adult patients. These findings support the role of systematic biopsies in multiple gastrointestinal sites to help distinguishing Crohn's ileitis from non-specific ileitis in paediatric and adult population.

  13. Ileal digestibility of amino acids in coproducts of corn processing into ethanol for pigs.

    PubMed

    Adeola, O; Ragland, D

    2012-12-01

    Five barrows with an average initial BW of 45 kg and fitted with a T-cannula at the distal ileum were fed 5 diets to determine the standardized ileal digestibility (SID) of AA in corn (Zea mays) distillers' dried grains (DDG), DDG with solubles (DDGS), high-protein DDG (HPDDG) and high-protein DDGS (HPDDGS). On a DM basis, the test ingredients contained 33.7% CP, 19.2% ADF, and 53.1% NDF for DDG; 30.3% CP, 11.8% ADF, and 40.6% NDF for DDGS; 62.5% CP, 28.4% ADF, and 45.1% NDF for HPDDG; and 52.4% CP, 17.4% ADF, and 30.4% NDF for HPDDGS. The 5 diets consisted of a N-free diet (NFD) and 4 semipurified diets, in which the test ingredient was the sole protein source with chromic oxide added at 5 g/kg as an indigestible marker, and fed for each of 5 periods. The NFD was used to determine basal endogenous AA losses. Each period consisted of a 5-d adjustment period and 2 d of ileal digesta collection for 10 h on each of day 6 and day 7. Amino acids in the test ingredients were well digested by pigs and SID of Lys for DDG, DDGS, HPDDG, and HPDDGS were 88.6, 79.9, 94.6, and 85.8%, respectively. Corresponding values for were Met 93.9, 92.8, 97.1, and 94.6%. The SID of Lys was greater (P < 0.05) in HPDDG than DDGS. In general, digestibility of AA in the high-protein coproduct of the dry grind processing of corn into ethanol was 2 to 8 percentage units more than in the regular coproduct and 2 to 9 percentage units less in the coproduct with added solubles.

  14. Effects of a phytogenic feed additive on growth performance and ileal nutrient digestibility in broiler chickens.

    PubMed

    Amad, A A; Männer, K; Wendler, K R; Neumann, K; Zentek, J

    2011-12-01

    A study was undertaken to examine the effects of a phytogenic feed additive (PFA) containing essential oils of thyme and star anise as lead active components on the growth performance and apparent ileal nutrient digestibility in broiler chickens. In total, 528 one-day-old Cobb male broilers were randomly divided into 4 dietary treatment groups with 6 replicate pens per treatment group (22 birds each). The dietary treatments were a control starter and grower basal diet without PFA or 150, 750, or 1,500 mg/kg of PFA. Body weight, weight gain, and feed intake were not significantly influenced by the feed additive, but the feed conversion ratio during the grower (22-42 d) and overall (1-42 d) periods improved linearly (P < 0.05) by the administration of PFA compared with that of the control diet. The average weights of the liver, heart, kidneys, and spleen were not significantly affected by the PFA. The results of the apparent ileal digestibility of crude ash, CP, crude fat, calcium, and phosphorus showed a linear increase (P < 0.05) related to the increase of PFA dose in the diet. Therefore, the means of digestibility of these nutrients were significantly higher in birds fed the PFA for all categories of age compared with the digestibility of these nutrients in the controls. In conclusion, the mode of action of the tested PFA can be explained by an improvement in the nutrient digestibility in the small intestine. The underlying physiological mechanisms, however, need to be characterized further.

  15. Association between gastro-intestinal symptoms and menstruation in patients with ileal pouches

    PubMed Central

    Bharadwaj, Shishira; Wu, Xian-rui; Barber, Matthew D.; Queener, Elaine; Graff, Lesley; Shen, Bo

    2014-01-01

    Background and aims: Gastro-intestinal (GI) symptoms are often experienced by healthy women during menstruation. An increased frequency of GI symptoms during menses has also been reported in women with irritable bowel syndrome or inflammatory bowel disease (IBD); however, IBD patients with restorative proctocolectomy and ileal pouch-anal anastomoses (IPAA) have not been studied. We aimed to examine the association between GI symptoms before and during menses in patients with IPAA, and to assess factors for exacerbation of GI symptoms in those patients. Methods: Adult women recorded in the Pouchitis Registry were invited to participate in a mailed survey. Participants reported on GI symptoms 1–5 days prior to- (pre-menses) and during the days of their menses in recent months. Demographic and clinical variables were obtained through the survey and chart review. Results: One hundred and twenty-eight (21.3%) out of 600 women with IPAA responded to the survey questionnaire. Forty-three (33.5%) were excluded for reasons including post-menopausal (n = 25), hysterectomy (n = 14) and use of contraceptives (n = 4). Abdominal pain (P = 0.001), diarrhea (P = 0.021), and urgency (P = 0.031) were more commonly reported during menses than pre-menses by the participants. Only a history of painful menses was significantly associated with increased GI symptoms during menses for patients with ileal pouch (odds ratio = 5.67; 95% confidence interval: 1.41–22.88; P = 0.015). Conclusion: GI symptoms such as abdominal pain, diarrhea, and urgency are commonly associated with menses in patients with ileo-anal pouch. Painful menses may be associated with worsening of GI symptoms. PMID:25016379

  16. Identification of cytosolic and microsomal bile acid-binding proteins in rat ileal enterocytes

    SciTech Connect

    Lin, M.C.; Kramer, W.; Wilson, F.A. )

    1990-09-05

    Studies were performed to determine the subcellular fractions and proteins involved in the intracellular transport of bile acids in rat ileal cells. The photolabile derivative 7,7-azo-taurocholate inhibited the Na(+)-dependent uptake of taurocholate into rat ileal enterocytes reversibly in the dark and irreversibly following photolysis. When photolabeled cells were submitted to subcellular fractionation, greatest radioactivity was found in the soluble protein (SP) fraction with decreasing radioactivity in the brush-border-(BBM), basolateral-(BLM), mitochondria-(MT), microsome-(MC), and Golgi-(GO) enriched fractions. Following trichloroacetic acid precipitation, delipidation, and correction for loss of marker enzyme activity, protein bound radioactivity was in SP greater than BBM greater than MC greater than BLM greater than GO greater than MT. When photolabeled cells were first fractionated and then submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a 99-kDa polypeptide was associated with BBM, 54- and 59-kDa polypeptides with BLM, 14-, 35-, 43-, 59-, and 68-kDa polypeptides with SP and a 20-kDa polypeptide with MC fractions. Immunoprecipitation with known antisera identified the 68-kDa polypeptide as albumin and the 43-kDa polypeptide as actin. No precipitation on the 14-kDa polypeptide was noted with anti-hepatic and anti-intestinal fatty acid-binding proteins. No precipitation of the 35-kDa polypeptide occurred with antibody to the hepatic cytosolic bile acid-binding protein. These studies reveal a previously unrecognized 20-kDa microsomal, and 14- and 35-kDa cytosolic bile acid-binding polypeptides which may be involved in the transcellular movement of bile acids.

  17. Recent progress in HIV vaccines inducing mucosal immune responses.

    PubMed

    Pavot, Vincent; Rochereau, Nicolas; Lawrence, Philip; Girard, Marc P; Genin, Christian; Verrier, Bernard; Paul, Stéphane

    2014-07-31

    In spite of several attempts over many years at developing a HIV vaccine based on classical strategies, none has convincingly succeeded to date. As HIV is transmitted primarily by the mucosal route, particularly through sexual intercourse, understanding antiviral immunity at mucosal sites is of major importance. An ideal vaccine should elicit HIV-specific antibodies and mucosal CD8⁺ cytotoxic T-lymphocyte (CTL) as a first line of defense at a very early stage of HIV infection, before the virus can disseminate into the secondary lymphoid organs in mucosal and systemic tissues. A primary focus of HIV preventive vaccine research is therefore the induction of protective immune responses in these crucial early stages of HIV infection. Numerous approaches are being studied in the field, including building upon the recent RV144 clinical trial. In this article, we will review current strategies and briefly discuss the use of adjuvants in designing HIV vaccines that induce mucosal immune responses.

  18. HIV and mucosal barrier interactions: consequences for transmission and pathogenesis.

    PubMed

    Burgener, Adam; McGowan, Ian; Klatt, Nichole R

    2015-10-01

    The mucosal barrier plays an integral function in human health as it is the primary defense against pathogens, and provides a critical transition between the external environment and the human internal body. In the context of HIV infection, the most relevant mucosal surfaces include those of the gastrointestinal (GI) and genital tract compartments. Several components help maintain the effectiveness of this mucosal surface, including the physical anatomy of the barrier, cellular immunity, soluble factors, and interactions between the epithelial barrier and the local microenvironment, including mucus and host microbiota. Any defects in barrier integrity or function can rapidly lead to an increase in acquisition risk, or with established infection may result in increased pathogenesis, morbidities, or mortality. Indeed, a key feature to all aspects of HIV infection from transmission to pathogenesis is disruption and/or dysfunction of mucosal barriers. Herein, we will detail the host-pathogen relationship of HIV and mucosal barriers in both of these scenarios.

  19. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... cells). Glutathione measurements are used in the diagnosis and treatment of certain drug-induced hemolytic (erythrocyte destroying) anemias due to an inherited enzyme deficiency. (b) Classification....

  20. 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

  1. Measurement of true ileal digestibility and total tract retention of phosphorus in corn and canola meal for broiler chickens.

    PubMed

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

    2014-02-01

    The study reported herein was conducted to determine and compare the nonphytate P, digestible P, and retainable P contents of corn and canola meal for broiler chickens. Four semipurified diets were formulated from each of ingredient to contain graded concentrations of nonphytate P. The experiment was conducted as a randomized complete block design with 4 weight blocks of 8 cages each (6 birds per cage). A total of 192 broilers (Ross 308), 21 d old, were assigned to the 8 test diets. Ileal digestibility and total tract retention coefficients of P were determined by the indicator and total collection methods, respectively, and linear regression method was used to determine the true P digestibility and true P retention coefficients. The apparent ileal digestibility of P in corn was influenced (quadratic, P < 0.05) by increasing dietary nonphytate P concentrations, whereas P retention was unaffected (P > 0.05). The apparent ileal P digestibility in broilers fed diets based on canola meal was similar (P > 0.05) at different P concentrations. Phosphorus retention in broilers fed diets based on canola meal (linear, P < 0.01) decreased with increasing P concentrations. True ileal P digestibility and true P retention coefficients of corn were determined to be 0.676 and 0.632, respectively. The corresponding values for canola meal were 0.469 and 0.486, respectively. In both ingredients, the determined true ileal digestibility and total tract retention coefficients were not different (P > 0.05). Total P, nonphytate P, true digestible P, and true retainable P contents of corn were determined to be 2.5, 0.8, 1.7, and 1.6 g/kg (as received), respectively. The corresponding values for canola meal were 9.7, 2.8, 4.6, and 4.7 g/kg (as received), respectively. The present data demonstrated that the regression method can be successfully used to measure true P digestibility of low and high P feed ingredients and that both true ileal digestibility and retention coefficients are

  2. 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

  3. Redo Ileal pouch-anal anastomosis combined with anti-TNF-α maintenance therapy for Crohn's disease with pelvic fistula: report of two cases.

    PubMed

    Araki, Toshimitsu; Okita, Yoshiki; Fujikawa, Hiroyuki; Ohi, Masaki; Tanaka, Koji; Inoue, Yasuhiro; Uchida, Keiichi; Mohri, Yasuhiko; Kusunoki, Masato

    2014-10-01

    Pouch failure has been reported to occur after ileal pouch-anal anastomosis for Crohn's disease. We report two cases of patients with Crohn's disease, who underwent redo ileal pouch-anal anastomosis (redo-IPAA) combined with anti-TNF-α maintenance therapy, with good functional results. The first patient, a man with presumed ulcerative colitis, suffered pelvic fistula recurrence and anastomotic dehiscence. He underwent redo-IPAA, at which time longitudinal ulcers were found. Infliximab was started 4 days postoperatively and continued. The second patient, a woman treated for ulcerative colitis, underwent laparoscopic IPAA 8 years later. After the development of a pelvic fistula, twisted mesentery of the ileal pouch was found intraoperatively and Crohn's disease was diagnosed. Adalimumab therapy resulted in fistula closure. Redo-IPAA was performed to normalize the twisted mesentery of the ileal pouch. No complications have been observed in either patient, both of whom have experienced good functional results after closure of the covering stomas.

  4. Mucosal drug delivery: membranes, methodologies, and applications.

    PubMed

    Song, Yifan; Wang, Yiping; Thakur, Rashmi; Meidan, Victor M; Michniak, Bozena

    2004-01-01

    In recent years, extensive research into novel forms of drug delivery has suggested that mucosal approaches offer a promising therapeutic alternative, especially for systemically acting drugs. Transmucosal drug delivery offers many benefits, including noninvasive administration, convenience, rapid onset, as well as elimination of hepatic first-pass metabolism. The investigated absorptive surfaces consist of the nasal, buccal, ocular, vaginal, and rectal mucosae. Among these, the nasal and buccal routes have proved the most promising to date. The bioavailability achieved mainly depends upon the pathophysiological state of the mucosa and the properties of both the drug and delivery systems. Various agents can increase the efficacy of transmucosal drug delivery. These include cyclodextrins, bile salts, surfactants, fusidic acid derivatives, microspheres, liposomes, and bioadhesive agents. The mechanisms of action, effectiveness, and toxicity profiles of these enhancers have been investigated extensively in both animal and human models.

  5. Cyclosporin metabolism by human gastrointestinal mucosal microsomes.

    PubMed Central

    Webber, I R; Peters, W H; Back, D J

    1992-01-01

    The in vitro metabolism of the immunosuppressant cyclosporin (CsA) by human gastrointestinal mucosal microsomes has been studied. Macroscopically normal intestinal (n = 4) and liver (n = 2) tissue was obtained from kidney transplant donors, and microsomes prepared. Intestinal metabolism was most extensive with duodenal protein (15% conversion to metabolites M1/M17 after 2 h incubation at 37 degrees C; metabolite measurement by h.p.l.c). Western blotting confirmed the presence of P-4503A (enzyme subfamily responsible for CsA metabolism) in duodenum and ileum tissue, but not in colon tissue. The results of this study indicate that the gut wall may play a role in the first-pass metabolism of CsA, and could therefore be a contributory factor to the highly variable oral bioavailability of CsA. PMID:1389941

  6. Mucosal cytokine network in inflammatory bowel disease

    PubMed Central

    Andoh, Akira; Yagi, Yuhki; Shioya, Makoto; Nishida, Atsushi; Tsujikawa, Tomoyuki; Fujiyama, Yoshihide

    2008-01-01

    Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by ongoing mucosal inflammation in which dysfunction of the host immunologic response against dietary factors and commensal bacteria is involved. The chronic inflammatory process leads to disruption of the epithelial barrier, and the formation of epithelial ulceration. This permits easy access for the luminal microbiota and dietary antigens to cells resident in the lamina propria, and stimulates further pathological immune cell responses. Cytokines are essential mediators of the interactions between activated immune cells and non-immune cells, including epithelial and mesenchymal cells. The clinical efficacy of targeting TNF-α clearly indicates that cytokines are the therapeutic targets in IBD patients. In this manuscript, we focus on the biological activities of recently-reported cytokines [Interleukin (IL)-17 cytokine family, IL-31 and IL-32], which might play a role through interaction with TNF-α in the pathophysiology of IBD. PMID:18777592

  7. Mucosal adaptation to aspirin induced gastric damage in humans. Studies on blood flow, gastric mucosal growth, and neutrophil activation.

    PubMed Central

    Konturek, J W; Dembinski, A; Stoll, R; Domschke, W; Konturek, S J

    1994-01-01

    The gastropathy associated with the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is named gastric adaptation. To assess the extent of mucosal damage by aspirin and subsequent adaptation the effects of 14 days of continuous, oral administration of aspirin (2 g per day) to eight healthy male volunteers was studied. To estimate the rate of mucosal damage, gastroscopy was performed before (day 0) and at days 3, 7, 14 of aspirin treatment. Gastric microbleeding and gastric mucosal blood flow were measured using laser Doppler flowmeter and mucosal biopsy specimens were taken for the estimation of tissue DNA synthesis and RNA and DNA concentration. In addition, the activation of neutrophils in peripheral blood was assessed by measuring their ability to associate with platelets. Aspirin induced acute damage mainly in gastric corpus, reaching at day 3 about 3.5 on the endoscopic Lanza score but lessened to about 1.5 at day 14 pointing to the occurrence of gastric adaptation. Mucosal blood flow increased at day 3 by about 50% in the gastric corpus and by 88% in the antrum. The in vitro DNA synthesis and RNA concentration, an index of mucosal growth, were reduced at day 3 but then increased to reach about 150% of initial value at the end of aspirin treatment. It is concluded that the treatment with aspirin in humans induces gastric adaptation to this agent, which entails the increase in mucosal blood flow, the rise in neutrophil activation, and the enhancement in mucosal growth. PMID:7959223

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

    PubMed Central

    2014-01-01

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

  9. Microbes and mucosal immune responses in asthma.

    PubMed

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

    2013-03-09

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

  10. The oral mucosal surface and blood vessels

    PubMed Central

    2013-01-01

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

  11. Maintenance of glutathione content is isolated hepatocyctes.

    PubMed Central

    Nińa, J; Hems, R; Krebs, H A

    1978-01-01

    1. During the standard procedure for the preparation of rat hepatocytes, about half of the cellular GSH (reduced glutathione) is lost. 2. This loss is prevented by the addition of 0.1 mM-EGTA (but no EDTA) to the perfusion medium. 3. On incubation with and without EGTA, isolated hepatocytes prepared in the presence of EGTA lose GSH. This loss is prevented by near-physiological concentrations of methionine or homocysteine, but not of cysteine. 4. Cysteine, at concentrations above 0.2 mM, causes a loss of GSH probably by non-enzymic formation of a mixed disulphide. 5. Serine together with methionine or homocystein increases GSH above the value in cells from starved rats in vivo. This is taken to suggest that cystathionine may be a cysteine donor in the synthesis of gamma-glutamylcysteine, the precursor of GSH. PMID:646804

  12. Mucositis and non-invasive markers of small intestinal function.

    PubMed

    Tooley, Katie L; Howarth, Gordon S; Butler, Ross N

    2009-05-01

    Mucositis is a common and debilitating side effect of chemotherapy that manifests due to the inability of chemotherapy agents to discriminate between normal and neoplastic cells. This results in ulcerating lesions lining the gastrointestinal tract. Moreover, the development of efficacious treatments for small intestinal mucositis has been hindered as the pathobiology of mucositis is still not fully understood. The small intestine is an extensive organ which is largely inaccessible by conventional means. Non-invasive biomarkers such as small intestinal permeability, H(2) breath tests, serum citrulline tests and the (13)C-sucrose breath test (SBT) have emerged as potential markers of small intestinal function. The SBT is emerging as the more appropriate biomarker to assess chemotherapy-induced mucositis in cancer patients and animal models, where it measures the decrease in sucrase activity associated with villus blunting and crypt disruption. The SBT has been successfully applied to detect mucositis induced by different classes of chemotherapy agents and has been used successfully to monitor small intestinal function with a range of candidate anti-mucositis treatments. We propose the SBT a superior biomarker of small intestinal function that could be successfully applied in clinical practice for monitoring the development of mucositis in cancer patients undergoing chemotherapy.

  13. 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.

  14. 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.

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

    PubMed Central

    KIYONO, Hiroshi; AZEGAMI, Tatsuhiko

    2015-01-01

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

  16. 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

  17. The effect of cottonseed condensed tannins on the ileal digestibility of amino acids in casein and cottonseed kernel.

    PubMed

    Yu, F; Moughan, P J; Barry, T N

    1996-05-01

    The effect of adding cottonseed hulls to casein- and cottonseed-kernel-based diets on the apparent and true ileal digestibility of N and amino acids, and the proportion of this effect accounted for by condensed tannin (CT), were determined using the growing rat. Sixty rats were allocated randomly to ten semipurified diets, containing either casein (four diets) or purified unheated solvent-extracted cottonseed kernel (six diets) as the sole protein source, with Cr2O3 added as an indigestible marker. Two of the casein diets contained no hulls whilst the remaining two diets contained 70 g cottonseed hulls/kg. Two of the cottonseed-kernel-based diets contained no hulls, with two containing 23 g hulls/kg and the remaining two containing 46 g hulls/kg. For each pair of diets, PEG was either included or excluded. The effect of CT was quantified by comparing control rats (-PEG; CT acting) with PEG-supplemented rats (+PEG; CT inactivated) at each level of dietary hulls. The rats were given their respective experimental diets for 14 d. Each rat was given the food ad libitum for 10 min hourly from 08.00 to 18.00 hours. On day 14, samples of digesta were collected at death from the terminal 150 mm of ileum at 7 h from the first meal. Apparent and true ileal digestibilities were calculated for DM, N and the individual amino acids. The principal finding was that the inclusion of hulls depressed the apparent and true ileal digestibilities of N and amino acids, but with the response differing between diets. With the casein-based diet the mean apparent and true ileal amino acid digestibilities were significantly depressed from 0.89 and 0.96 to 0.85 and 0.92 respectively, by the inclusion of 70 g hulls/kg in the diet, and addition of PEG then restored these to 0.89 and 0.95. All of the depression could be explained by the CT content of the hulls. However, with the cottonseed-kernel-based diet the responses fell into three categories. The apparent and true ileal digestibilities of

  18. Protective effect of hydrogen sulfide against cold restraint stress-induced gastric mucosal injury in rats.

    PubMed

    Aboubakr, Esam M; Taye, Ashraf; El-Moselhy, Mohamed A; Hassan, Magdy K

    2013-12-01

    Hydrogen sulfide (H2S) is an endogenous gaseous mediator plays a potential role in modulating gastric inflammatory responses. However, its putative protective role remains to be defined. The present study aimed to evaluate role of the exogenously released and endogenously synthesized H2S in cold restraint stress (CRS)-induced oxidative gastric damage in rats. Rats were restrained, and maintained at 4 °C for 3 h. The H2S donor, sodium hydrosulfide (NaHS) (60 μmol/kg) was injected intraperitoneally (i.p.) before CRS. Our results revealed that NaHS pretreatment significantly attenuated ulcer index, free and total acid output, and pepsin activity in gastric juice along with decreased gastric mucosal carbonyl content and reactive oxygen species production. This was accompanied by increased gastric juice pH and mucin concentration in addition to restoring the deficits in the gastric reduced glutathione, catalase as well as superoxide dismutase enzyme activities. NaHS pretreatment markedly reduced the serum level of tumor necrosis factor (TNF-α) and myeloperoxidase activity compared to CRS-non-treated. Moreover, NaHS preadministration significantly abrogated the inflammatory and the deleterious responses of gastric mucosa in CRS. The protective effects of H2S were confirmed by gastric histopathological examination. However, pretreatment with the H2S-synthesizing enzyme, cystathionine-gamma-lyase inhibitor, beta-cyano-L-alanine (50 mg/kg, i.p.) reversed the gastroprotection afforded by the endogenous H2S. Collectively, our results suggest that H2S can protect rat gastric mucosa against CRS-induced gastric ulceration possibly through mechanisms that involve anti-oxidant and anti-inflammatory actions alongside enhancement of gastric mucosal barrier and reduction in acid secretory parameters.

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

    PubMed

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

    2017-01-04

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

  20. 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.

  1. The physiologic effects of ileal reservoirs and efferent conduits complementing ileoanal anastomosis: an experimental study in dogs.

    PubMed

    Rosemurgy, A S; Schraut, W H; Block, G E

    1983-10-01

    S-shaped ileal reservoirs (SSRs) and double-barreled ileal reservoirs (DBRs) of equal size were placed 6 or 2 cm from the anus and evaluated over 1 year for their ability to improve the functional incontinence noted after an ileoanal anastomosis (IAA). Compared to straight IAA, both reservoirs prolonged intestinal transit (235 minutes versus 135 minutes, P less than 0.001) and alleviated frequency without causing nutritional abnormalities. The capacity of the reservoirs was greater than that of a comparable length of distal ileum in dogs (n = 6) with straight IAA (304 +/- 16 ml versus 102 +/- 2 ml, P less than 0.001). The SSRs (n = 9), in contrast to the DBRs (n = 10), developed excessive volume capacity (360 +/- 30 ml versus 254 +/- 104 ml, P less than 0.01) and obstructive complications. Reservoirs with 6 cm efferent conduits (n = 13), in contrast to those with a 2 cm efferent conduit (n = 6), underwent marked dilatation (334 +/- 24 ml versus 238 +/- 13 ml, P less than 0.005). Electromyography and manometry revealed the DBRs to be more contractile than the SSRs but less than ileum proximal to the anus in dogs with a straight IAA. Ileal reservoirs improve results after IAA. Reservoirs should be complaint and yet contractile (e.g., DBR) so as to discourage excessive dilatation, which is the harbinger of obstruction. Ileal conduits facilitate reservoir placement, but if longer than 2 cm they excessively impeded reservoir emptying, predisposing to excessive reservoir dilatation and obstruction. A DBR with a 2 cm efferent conduit results in continence without obstructive problems.

  2. Functional changes in nonadrenergic, noncholinergic inhibitory neurons in ileal circular smooth muscle after small bowel transplantation in rats.

    PubMed

    Shibata, C; Balsiger, B M; Anding, W J; Duenes, J A; Miller, V M; Sarr, M G

    1998-11-01

    This experiment was designed to determine mechanisms of change in nonadrenergic, noncholinergic (NANC) inhibitory neurons in the ileum after small bowel transplantation (SBT) in the rat and whether nitric oxide (NO) serves as an important NANC inhibitory neurotransmitter in the rat ileum. Eight groups of rats (N > or =8 rats/group) were studied: neurally intact unoperated controls; rats one week after anesthesia and sham celiotomy; and separate groups one and eight weeks after either 40 min of cold ischemia of the jejunoileum, combined jejunal and ileal intestinal transection/reanastomosis, or orthotopic SBT of the entire jejunoileum. Contractile activity was evaluated in full-thickness ileal circular muscle strips under isometric conditions. Spontaneous activity did not differ among groups. In all groups, exogenous NO, NG-monomethyl-L-arginine (L-NMMA, an NO synthase inhibitor), and methylene blue (soluble guanylate cyclase inhibitor) had no effect on spontaneous activity, while 8-bromocyclic guanosine monophosphate (8Br-cGMP) inhibited contractile activity in all groups. Low frequency (2-10 Hz) electrical field stimulation (EFS) inhibited contractile activity only in control and SBT groups; L-NMMA and methylene blue did not alter the response to EFS in any group. These results suggest that each aspect of the SBT procedure, ischemia/reperfusion injury, disruption of enteric neural continuity by intestinal transection, and extrinsic denervation, alter function of enteric ileal inhibitory neurons separately early (one week) after operation. NO, a known inhibitory neurotransmitter in other gut regions, does not affect ileal circular muscle in neurally intact tissue nor mediate functional changes in inhibitory nerve function nor smooth muscle contractility after SBT.

  3. The role of macrophages in the removal of apoptotic B-cells in the sheep ileal Peyer's patch.

    PubMed

    Bhogal, Hardeep S; Kennedy, Laurie J; Babic, Kelly; Reynolds, John D

    2004-06-01

    In the process of generating the cells that populate the sheep's B-cell pool, the ileal Peyer's patch (PP) produces an immense number of B-cells and then destroys most of them by apoptosis. Rapid clearance of these apoptotic cells is essential for tissue homeostasis and for preventing pathology. Macrophages comprise a small percentage of cells in the follicles. They resemble macrophages found in other tissues and can be identified by the expression of MHC Class II and CD14. In this study, enriched macrophages co-cultured with apoptotic ileal PP cells showed increased DNA content as they ingested apoptotic cells. The higher the proportion of apoptotic cells in culture the greater the increase in DNA content of the macrophages. This occurred when B-cell apoptosis was initiated by a period in culture or in response to treating the animals with steroids. Thus, macrophages resident in the ileal PP follicle mediate the phagocytosis and removal of discarded B-cells.

  4. The Bacteriomes of Ileal Mucosa and Cecal Content of Broiler Chickens and Turkeys as Revealed by Metagenomic Analysis

    PubMed Central

    Wei, Shan; Lilburn, Michael

    2016-01-01

    The gastrointestinal (GI) bacteriome of poultry is important in host nutrition and health, but its diversity and composition remain poorly characterized. In this study we phylogenetically characterized the bacteriome in the cecal contents and ileal mucosa of chickens and turkeys using metagenomics empowered by pyrosequencing technique. >95% coverage of bacterial diversity was achieved except for the turkey ileal mucosa. Collectively, 3,401 and 125 operational taxonomy units (OTU, defined at a 0.03 phylogenetic distance) in chicken, and 1,687 and 16 OTUs in turkey were identified from the cecal content and the ileal mucosa, respectively. Besides those previously reported, 39 and 50 additional genera of bacteria were identified in the chicken and turkey cecal bacteriome, respectively. Although the GI bacteriomes of the same region in both species exhibited greater similarity than the bacteriomes of different regions within each species, broiler chickens and turkeys harbor a distinct intestinal bacteriome. Such difference may suggest different dietary interventions for bacteriome modulation for enhanced nutrient utilization and gut health. The results may also be useful in developing prebiotics, probiotics, and analytical tools (e.g., phylochips). We also determined the variation in the number of OTUs and variability between two independent pyrosequencing runs and two data processing pipelines. PMID:28115936

  5. Short-term dietary phosphate restriction up-regulates ileal fibroblast growth factor 15 gene expression in mice

    PubMed Central

    Nakahashi, Otoki; Yamamoto, Hironori; Tanaka, Sarasa; Kozai, Mina; Takei, Yuichiro; Masuda, Masashi; Kaneko, Ichiro; Taketani, Yutaka; Iwano, Masayuki; Miyamoto, Ken-ichi; Takeda, Eiji

    2014-01-01

    Members of the fibroblast growth factor (FGF) 19 subfamily, including FGF23, FGF15/19, and FGF21, have a role as endocrine factors which influence the metabolism of inorganic phosphate (Pi) and vitamin D, bile acid, and energy. It has been reported that dietary Pi regulates circulating FGF23. In this study, the short-term effects of dietary Pi restriction on the expression of FGF19 subfamily members in mice were analyzed. An initial analysis confirmed plasma FGF23 levels positively correlated with the amount of dietary Pi. On the other hand, ileal Fgf15 gene expression, but not hepatic Fgf21 gene expression, was up-regulated by dietary Pi restriction. In addition, we observed the increase of plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] levels by dietary Pi restriction, and the up-regulation of ileal Fgf15 mRNA expression by 1,25(OH)2D3 and vitamin D receptor (VDR). Importantly, dietary Pi restriction-induced Fgf15 gene expression was prevented in VDR-knockout mice. Furthermore, diurnal variations of plasma triglyceride concentrations and hepatic mRNA expression of the bile acid synthesis enzyme Cyp7a1 as one of Fgf15 negative target genes was influenced by dietary Pi restriction. These results suggest that dietary Pi restriction up-regulates ileal Fgf15 gene expression through 1,25(OH)2D3 and VDR, and may affect hepatic bile acid homeostasis. PMID:24688219

  6. 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.

  7. 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...

  8. Molecular ecological analysis of porcine ileal microbiota responses to antimicrobial growth promoters.

    PubMed

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

    2003-12-01

    Cultivation-independent microbial molecular ecology approaches were used to examine the effects of antibiotic growth promoters on the pig ileal microbiota. Five-week-old barrows were fitted with a simple T-cannula at the distal ileum. Three diets meeting or exceeding the minimum nutrient requirements were fed for 5 wk and supplemented as follows: 1) negative control (no antibiotic; n = 5), 2) continuous tylosin administration (n = 5), and 3) an antibiotic rotation sequence (wk 1, chlorotetracycline sulfathiazole penicillin; wk 2, bacitracin and roxarsone; wk 3, lincomycin; wk 4, carbadox; wk 5, virginiamycin; n = 5). Ileal luminal contents were collected for DNA isolation at the end of each of the 5 wk of the testing period. The V3 region of 16S rDNA was amplified by PCR and analyzed via denaturing gradient gel electrophoresis (DGGE) and quantitative polymerase chain reaction (qPCR). Resulting PCR-DGGE band numbers (bacterial species) were counted, and the banding patterns analyzed by calculating Sorenson's pairwise similarity coefficients (C(S)), an index measuring bacterial species in common among samples. Band numbers and total bacterial DNA concentrations decreased (P < 0.05) temporally in antibiotic-treated pigs compared with controls. Comparisons between treatments yielded low intertreatment C(S) indices, indicating treatment-dependent alterations in banding patterns, whereas intratreatment comparisons revealed increased homogeneity in antibiotic-treated vs. control pigs. Sequence analysis of treatment-specific bands identified three Lactobacillus, one Streptococcus, and one Bacillus species that were diminished with antibiotic rotation treatment, whereas tylosin selected for the presence of L. gasseri. Lactobacillus-specific qPCR was performed and analyzed as a percentage of total bacteria to further evaluate the effects of antibiotic administration on this genus. Total bacteria were decreased (P < 0.05) by tylosin and rotation treatments, whereas the

  9. 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

  10. 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.

  11. 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; Lærke, 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

  12. Gastrointestinal mucositis: the role of MMP-tight junction interactions in tissue injury.

    PubMed

    Al-Dasooqi, Noor; Wardill, Hannah R; Gibson, Rachel J

    2014-07-01

    Chemotherapy for cancer causes significant gut toxicity known as mucositis. The pathogenesis of mucositis is ill defined. Recent clinical research guidelines have highlighted epithelial junctional complexes as emerging targets within mucositis research. Given the robust biological evidence linking tight junctions and matrix metalloproteinases, key mediators of mucositis, tight junction proteins have received significant attention. Despite this, the link between tight junctions, matrix metalloproteinases and mucositis development is yet to be established. This critical review therefore aims to describe the role of matrix metalloproteinases in mucositis, and how matrix metalloproteinase-dependent tight junction disruption may contribute to the pathobiology of mucositis.

  13. 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...

  14. [Mucositis in head and neck cancer patients undergoing radiochemotherapy].

    PubMed

    Santos, Renata Cristina Schmidt; Dias, Rodrigo Souza; Giordani, Adelmo José; Segreto, Roberto Araújo; Segreto, Helena Regina Comodo

    2011-12-01

    The objective of present study was to classify oral mucositis according to the Common Toxicity Criterion (CTC) international parameters in head and neck tumor patients simultaneously treated with radio and chemotherapy, and characterize a patient profile in our area, observing the individuals' habits, tumor characteristics, treatment protocol and acute reaction intensity. Fifty patients undergoing simultaneous 66 to 70 Gy megavoltage radiotherapy and cisplatin/carboplatin chemotherapy were evaluated in this study. Weekly evaluations of the degree of mucositis were perfoemed according to CTC, a four-degree ordinal scale; 36% of all patients and 100% of those with diabetes discontinued treatment due to mucositis, showing that this pathology contributes to the severity of mucositis.

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

    PubMed Central

    Deane, Kevin D.; Scher, Jose U.

    2016-01-01

    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

  16. Alleviating mucositis: are we on track for a novel therapeutic?

    PubMed

    Lalla, Rajesh V

    2015-02-01

    Oral and gastrointestinal mucositis has emerged as an important toxicity of cancer therapy. In addition to supportive care measures, agents for the prevention or treatment of mucositis in specific patient populations are described in the evidence-based clinical practice guidelines published by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. However, there still remains an unmet clinical need for preventive and therapeutic agents in several patient populations. The successful development of such agents will rely on our improved understanding of the pathogenic mechanisms underlying mucositis. Studies are also underway on novel delivery mechanisms and risk prediction models that can facilitate the selective use of interventions for mucositis in a targeted and cost-effective manner. A large number of agents are at various stages in the clinical development pipeline. Enhanced management of this dose-limiting toxicity will allow the delivery of optimal cancer therapy and improve patient prognosis.

  17. Prevention of acute gastric mucosal lesions by Solcoseryl.

    PubMed

    Brzozowski, T; Radecki, T; Sendur, R; Gustaw, P; Konturek, S J

    1987-04-01

    Solcoseryl, a deproteinized extract from calf blood containing various biologically active substances, has been reported to promote the healing of skin wounds and gastric ulceration In this study, the gastroprotective effects of Solcoseryl vis-a-vis acute gastric mucosal damage were examined in rats. Solcoseryl significantly reduced the formation of acute lesions induced by intragastric application of absolute ethanol or acidified taurocholate and by water immersion and restraint stress, but failed to affect those caused by acidified aspirin. Since Solcoseryl did not offer protection in the absence of mucosal prostaglandins (PG) e.g. in aspirin-induced gastric damage, it is likely that PG may be involved in the observed gastroprotective activity of the drug. Solcoseryl failed to affect gastric acid or pepsin secretion, but increased mucosal blood flow. Thus PG generated by Solcoseryl might contribute to the maintenance of the observed mucosal microcirculation and the prevention of lesion formation by corrosive substances and stress conditions.

  18. 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

  19. Ca2+-independent contraction of longitudinal ileal smooth muscle is potentiated by a zipper-interacting protein kinase pseudosubstrate peptide.

    PubMed

    Ihara, Eikichi; Moffat, Lori; Borman, Meredith A; Amon, Jennifer E; Walsh, Michael P; MacDonald, Justin A

    2009-08-01

    As a regulator of smooth muscle contraction, zipper-interacting protein kinase (ZIPK) can directly phosphorylate the myosin regulatory light chains (LC20) and produce contractile force. Synthetic peptides (SM-1 and AV25) derived from the autoinhibitory region of smooth muscle myosin light chain kinase can inhibit ZIPK activity in vitro. Paradoxically, treatment of Triton-skinned ileal smooth muscle strips with AV25, but not SM-1, potentiated Ca2+-independent, microcystin- and ZIPK-induced contractions. The AV25-induced potentiation was limited to ileal and colonic smooth muscles and was not observed in rat caudal artery. Thus the potentiation of Ca2+-independent contractions by AV25 appeared to be mediated by a mechanism unique to intestinal smooth muscle. AV25 treatment elicited increased phosphorylation of LC20 (both Ser-19 and Thr-18) and myosin phosphatase-targeting subunit (MYPT1, inhibitory Thr-697 site), suggesting involvement of a Ca2+-independent LC20 kinase with coincident inhibition of myosin phosphatase. The phosphorylation of the inhibitor of myosin phosphatase, CPI-17, was not affected. The AV25-induced potentiation was abolished by pretreatment with staurosporine, a broad-specificity kinase inhibitor, but specific inhibitors of Rho-associated kinase, PKC, and MAPK pathways had no effect. When a dominant-negative ZIPK [kinase-dead ZIPK((1-320))-D161A] was added to skinned ileal smooth muscle, the potentiation of microcystin-induced contraction by AV25 was blocked. Furthermore, pretreatment of skinned ileal muscle with SM-1 abolished AV25-induced potentiation. We conclude, therefore, that, even though AV25 is an in vitro inhibitor of ZIPK, activation of the ZIPK pathway occurs following application of AV25 to permeabilized ileal smooth muscle. Finally, we propose a mechanism whereby conformational changes in the pseudosubstrate region of ZIPK permit augmentation of ZIPK activity toward LC(20) and MYPT1 in situ. AV25 or molecules based on its structure

  20. Analysis of an ethanol precipitate from ileal digesta: evaluation of a method to determine mucin.

    PubMed

    Miner-Williams, Warren M; Moughan, Paul J; Fuller, Malcolm F

    2013-11-06

    The precipitation of mucin using high concentrations of ethanol has been used by many researchers while others have questioned the validity of the technique. In this study, analysis of an ethanol precipitate, from the soluble fraction of ileal digesta from pigs was undertaken using molecular weight profiling and polyacrylamide gel electrophoresis. The precipitate contained 201 mg·g⁻¹ protein, 87% of which had a molecular weight >20 KDa. Polyacrylamide gel electrophoresis stained with Coomassie blue and periodic acid/Schiff, revealed that most glycoprotein had a molecular weight between 37-100 KDa. The molecular weight of glycoprotein in the precipitate was therefore lower than that of intact mucin. These observations indicated that the glycoprotein in the ethanol precipitate was significantly degraded. The large amount of protein and carbohydrate in the supernatant from ethanol precipitation indicated that the precipitation of glycoprotein was incomplete. As a method for determining the concentration of mucin in digesta, ethanol precipitation is unreliable.

  1. Endoscopic treatment of leak at the tip of the “J” ileal pouch

    PubMed Central

    Kochhar, Gursimran Singh; Shen, Bo

    2017-01-01

    Background and study aims The tip of the “J” of the ileal pouch is the vulnerable location for leak after restorative proctocolectomy, which has normally been treated with surgery. We aimed to describe a novel endoscopic method to treat the same. Patients and methods A cohort of 12 consecutive patients with a leak at the tip of the “J” was identified in our prospectively maintained Pouch Registry. The endoscopic over-the-scope clipping (OTSC) system was used for the closure of the leak. Results Eight patients (66.6 %) achieved complete closure of the leak documented by endoscopy confirmed with guidewire and/or contrasted pouchogram, with 6 requiring a single endoscopic session and 2 undergoing a repeat session. Four patients (33.3 %) had a persistent leak and required surgical intervention, of whom 1 developed abscess in the pre-spine region 14 days after the endoscopic procedure and underwent pouch revision surgery. Conclusions OSTC appears to be safe and effective in treating the leak at the tip of the “J” in the majority of patients. PMID:28180150

  2. Human papillomavirus DNA in oral mucosal lesions.

    PubMed

    Giovannelli, Lucia; Campisi, Giuseppina; Lama, Anna; Giambalvo, Ornella; Osborn, John; Margiotta, Valerio; Ammatuna, Pietro

    2002-03-15

    This study determined the presence of human papillomavirus (HPV) DNA in oral mucosa cells from 121 patients with different types of oral mucosal lesions (13 squamous cell carcinomas, 59 potentially malignant lesions, 49 benign erosive ulcerative lesions) and from 90 control subjects. HPV DNA was detected by nested polymerase chain reaction, and genotype was determined by DNA sequencing. HPV prevalence was 61.5% in carcinomas, 27.1% in potentially malignant lesions, 26.5% in erosive ulcerative lesions, and 5.5% in control subjects. The risk of malignant or potentially malignant lesions was associated with HPV and was statistically significant. HPV-18 was found in 86.5% of HPV-positive lesions but was not associated with a particular type of lesion and was found in 80% of the HPV-positive control subjects. HPV infection was related to older age but not to sex, smoking, or alcohol use; the presence of lesions in the oral cavity increased the risk of HPV infection.

  3. Idiopathic mucosal penile squamous papillomas in dogs.

    PubMed

    Cornegliani, Luisa; Vercelli, Antonella; Abramo, Francesca

    2007-12-01

    A new papillomatous clinical entity is described affecting the penile mucosa of dogs. The animals, 11 male dogs of different breeds, ageing from 6 to 13 years, were presented for genital mass and occasional haematuria. Surgical incision of the prepuce skin of the anaesthetized dogs showed the presence of single pedunculated, soft, pink-red, cauliflower-like masses arising from the penile mucosa, with diameter ranging from 2 to 8 cm. In all cases, histopathological examination of the excised masses showed normal epithelial differentiation with digitiform expansion of all the layers and elongated rete ridges slanted towards the periphery of the lesion. Evidence of ballooning degeneration or basophilic intranuclear inclusion bodies was not found. Both immunohistochemistry and polymerase chain reaction techniques failed to reveal papillomavirus. According to the histological World Health Organization classification of papillomatous lesions and due to the lack of evidence of a viral origin the masses were identified as idiopathic mucosal penile squamous papillomas. Urinary problems resolved after surgical excision, haematuria was therefore considered secondary to ulceration of the papillated masses.

  4. 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 phenotypes—airway inflammation and spontaneous infection—may 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

  5. Mucosal disease series. Number IV. Erythema multiforme.

    PubMed

    Farthing, P; Bagan, J-V; Scully, C

    2005-09-01

    Erythema multiforme (EM) is an acute mucocutaneous hypersensitivity reaction characterised by a skin eruption, with or without oral or other mucous membrane lesions. Occasionally EM may involve the mouth alone. EM has been classified into a number of different variants based on the degree of mucosal involvement and the nature and distribution of the skin lesions. EM minor typically affects no more than one mucosa, is the most common form and may be associated with symmetrical target lesions on the extremities. EM major is more severe, typically involving two or more mucous membranes with more variable skin involvement - which is used to distinguish it from Stevens-Johnson syndrome (SJS), where there is extensive skin involvement and significant morbidity and a mortality rate of 5-15%. Both EM major and SJS can involve internal organs and typically are associated with systemic symptoms. Toxic epidermal necrolysis (TEN) may be a severe manifestation of EM, but some experts regard it as a discrete disease. EM can be triggered by a number of factors, but the best documented is preceding infection with herpes simplex virus (HSV), the lesions resulting from a cell mediated immune reaction triggered by HSV-DNA. SJS and TEN are usually initiated by drugs, and the tissue damage is mediated by soluble factors including Fas and FasL.

  6. Mucosal immune responses following intestinal nematode infection

    PubMed Central

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

    2014-01-01

    In most natural environments, the large majority of mammals harbour parasitic helminths that often live as adults within the intestine for prolonged periods (1–2 years) 1. Although these organisms have been eradicated to a large extent within westernized human populations, those living within rural areas of developing countries continue to suffer from high infection rates. Indeed, recent estimates indicate that approximately 2·5 billion people worldwide, mainly children, currently suffer from infection with intestinal helminths (also known as geohelminths and soil-transmitted helminths) 2. Paradoxically, the eradication of helminths is thought to contribute to the increased incidence of autoimmune diseases and allergy observed in developed countries. In this review, we will summarize our current understanding of host–helminth interactions at the mucosal surface that result in parasite expulsion or permit the establishment of chronic infections with luminal dwelling adult worms. We will also provide insight into the adaptive immune mechanisms that provide immune protection against re-infection with helminth larvae, a process that is likely to be key to the future development of successful vaccination strategies. Lastly, the contribution of helminths to immune modulation and particularly to the treatment of allergy and inflammatory bowel disease will be discussed. PMID:25201407

  7. Berberine Reduces Uremia-Associated Intestinal Mucosal Barrier Damage.

    PubMed

    Yu, Chao; Tan, Shanjun; Zhou, Chunyu; Zhu, Cuilin; Kang, Xin; Liu, Shuai; Zhao, Shuang; Fan, Shulin; Yu, Zhen; Peng, Ai; Wang, Zhen

    2016-11-01

    Berberine is one of the main active constituents of Rhizoma coptidis, a traditional Chinese medicine, and has long been used for the treatment of gastrointestinal disorders. The present study was designed to investigate the effects of berberine on the intestinal mucosal barrier damage in a rat uremia model induced by the 5/6 kidney resection. Beginning at postoperative week 4, the uremia rats were treated with daily 150 mg/kg berberine by oral gavage for 6 weeks. To assess the intestinal mucosal barrier changes, blood samples were collected for measuring the serum D-lactate level, and terminal ileum tissue samples were used for analyses of intestinal permeability, myeloperoxidase activity, histopathology, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity. Berberine treatment resulted in significant decreases in the serum D-lactate level, intestinal permeability, intestinal myeloperoxidase activity, and intestinal mucosal and submucosal edema and inflammation, and the Chiu's scores assessed for intestinal mucosal injury. The intestinal MDA level was reduced and the intestinal SOD activity was increased following berberine treatment. In conclusion, berberine reduces intestinal mucosal barrier damage induced by uremia, which is most likely due to its anti-oxidative activity. It may be developed as a potential treatment for preserving intestinal mucosal barrier function in patients with uremia.

  8. 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.

  9. Nocifensive Behaviors in Mice with Radiation-Induced Oral Mucositis.

    PubMed

    Nolan, Michael W; Long, C Tyler; Marcus, Karen L; Sarmadi, Shayan; Roback, Donald M; Fukuyama, Tomoki; Baeumer, Wolfgang; Lascelles, B Duncan X

    2017-02-10

    Oral mucositis can result in significant dysphagia, and is the most common dose-limiting acute toxicity in head and neck cancer patients receiving chemoradiotherapy. There is a critical need to determine the cellular and molecular mechanisms that underlie radiotherapy-associated discomfort in patients with mucositis. The objective was to induce oral mucositis in mice, using a clinical linear accelerator, and to quantify resultant discomfort, and characterize peripheral sensitization. A clinical linear accelerator was used to deliver ionizing radiation to the oral cavity of mice. Mucositis severity scoring, and various behavioral assays were performed to quantify bouts of orofacial wiping and scratching, bite force, gnawing behavior and burrowing activity. Calcium imaging was performed on neurons of the trigeminal ganglia. Glossitis was induced with a single fraction of at least 27 Gy. Body weight decreased and subsequently returned to baseline, in concert with development and resolution of mucositis, which was worst at day 10 and 11 postirradiation, however was resolved within another 10 days. Neither bite force, nor gnawing behavior were measurably affected. However, burrowing activity was decreased, and both facial wiping and scratching were increased while mice had visible mucositis lesions. Sensory nerves of irradiated mice were more responsive to histamine, tumor necrosis factor alpha and capsaicin. Radiation-induced glossitis is associated with hyper-reactivity of sensory neurons in the trigeminal ganglia of mice, and is accompanied by several behaviors indicative of both itch and pain. These data validate an appropriate model for cancer treatment related discomfort in humans.

  10. [New routes of administration: epidermal, transcutaneous mucosal ways of vaccination].

    PubMed

    Denis, François; Alain, Sophie; Ploy, Marie-Cécile

    2007-04-01

    A successful vaccine triggers the interaction of various cells of the immune system as does a regular immune response. It is thus necessary to introduce the vaccine antigens into an anatomic site where they will contact immune cells. The route of administration is thus critical for the outcome of vaccination. Intramuscular or subcutaneous injections are the most popular. Antigens injected intramuscularly can form persistent precipitates that are dissolved and re-absorbed relatively slowly. If injecting antigens is a quick, easy and reproducible way to vaccination, it requires trained personnel. Alternatives exist, through non-invasive formulations which allow administration by the patient or a third party with no particular expertise. The skin, especially its epidermal layer, is an accessible and competent immune environment and an attractive target for vaccine delivery, through transcutaneous delivery or immunostimulant patches. Mucosal immunization is another strategy: its major rationale is that organisms invade the body via mucosal surfaces. Therefore, local protection at mucosal surface as well as systemic defense is beneficial. Various formulations of mucosal vaccines have been developed, such as the Sabin oral polio vaccine (OPV), rotavirus vaccines, cold-adapted influenza vaccines or vaccine against typhoid fever. Thus we are entering in an era where mucosal and transcutaneous immunisation will play an important role in disease management. However, it has not been so easy to obtain regulatory approval for mucosal or transcutaneous formulations and needle-based vaccines continue to dominate the market.

  11. Oral mucositis in children suffering from acute lymphoblastic leukaemia

    PubMed Central

    2012-01-01

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

  12. 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.

  13. 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-h cycle 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

  14. Cellular glutathione peroxidase deficiency and endothelial dysfunction.

    PubMed

    Forgione, Marc A; Weiss, Norbert; Heydrick, Stanley; Cap, André; Klings, Elizabeth S; Bierl, Charlene; Eberhardt, Robert T; Farber, Harrison W; Loscalzo, Joseph

    2002-04-01

    Cellular glutathione peroxidase (GPx-1) is the most abundant intracellular isoform of the GPx antioxidant enzyme family. In this study, we hypothesized that GPx-1 deficiency directly induces an increase in vascular oxidant stress, with resulting endothelial dysfunction. We studied vascular function in a murine model of homozygous deficiency of GPx-1 (GPx-1(-/-)). Mesenteric arterioles of GPx-1(-/-) mice demonstrated paradoxical vasoconstriction to beta-methacholine and bradykinin, whereas wild-type (WT) mice showed dose-dependent vasodilation in response to both agonists. One week of treatment of GPx-1(-/-) mice with L-2-oxothiazolidine-4-carboxylic acid (OTC), which increases intracellular thiol pools, resulted in restoration of normal vascular reactivity in the mesenteric bed of GPx-1(-/-) mice. We observed an increase of the isoprostane iPF(2alpha)-III, a marker of oxidant stress, in the plasma and aortas of GPx-1(-/-) mice compared with WT mice, which returned toward normal after OTC treatment. Aortic sections from GPx-1(-/-) mice showed increased binding of an anti-3-nitrotyrosine antibody in the absence of frank vascular lesions. These findings demonstrate that homozygous deficiency of GPx-1 leads to impaired endothelium-dependent vasodilator function presumably due to a decrease in bioavailable nitric oxide and to increased vascular oxidant stress. These vascular abnormalities can be attenuated by increasing bioavailable intracellular thiol pools.

  15. 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

  16. Glutathione and glutathione-related enzymes in rats exposed to dimethoate and/or pyrantel.

    PubMed

    Spodniewska, A

    2014-01-01

    The study was undertaken to examine the effect of single and combined administration of dimethoate (an OP insecticide) and pyrantel embonate (an anthelmintic agent) on the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx) and glutathione reductase (GR) in rats. Dimethoate (Group I) was administered to rats at a dose of 1/10 LD50 for 5 consecutive days and pyrantel embonate (Group II) at a dose of 1/5 LD50 for 3 consecutive days. The animals of group III were given both of the mentioned above compounds in the same manner as group I and II, but pyrantel embonate was applied on day 3, 4, and 5 from the beginning of dimethoate intoxication. Material from 6 rats randomly selected from each group was obtained after 3, 6 and 12 hours and 2, 7 and 14 days following the last applied dose of the compounds under study. It was found that application of pyrantel embonate caused only slight changes in the analysed parameters i.e. GSH, GPx and GR. Dimethoate administration caused disturbances in the antioxidative system manifested as a decrease in GSH concentration in the liver (max.--37.7% after 6 hours) and an increase of GPx and GR activities in erythrocytes (max.--21.7% and 29.6% after 3 hours, respectively), compared to the control group. The profile of changes after combined intoxication was similar, but their intensity was higher compared to the group of animals exposed to dimethoate only. Based on current studies, it was concluded that both dimethoate and pyrantel embonate at the applied doses showed a pro-oxidative activity.

  17. Glutathione redox dynamics and expression of glutathione-related genes in the developing embryo

    PubMed Central

    Timme-Laragy, Alicia R.; Goldstone, Jared V.; Imhoff, Barry R.; Stegeman, John J.; Hahn, Mark E.; Hansen, Jason M.

    2013-01-01

    Embryonic development involves dramatic changes in cell proliferation and differentiation that must be highly coordinated and tightly regulated. Cellular redox balance is critical for cell fate decisions, but it is susceptible to disruption by endogenous and exogenous sources of oxidative stress. The most abundant endogenous non-protein antioxidant defense molecule is the tri-peptide glutathione (γ-glutamyl-cysteinylglycine, GSH), but the ontogeny of GSH concentration and redox state during early life stages is poorly understood. Here, we describe the GSH redox dynamics during embryonic and early larval development (0–5 days post-fertilization) in the zebrafish (Danio rerio), a model vertebrate embryo. We measured reduced and oxidized glutathione (GSH, GSSG) using HPLC, and calculated the whole embryo total glutathione (GSHT) concentrations and redox potentials (Eh) over 0–120 hours of zebrafish development (including mature oocytes, fertilization, mid-blastula transition, gastrulation, somitogenesis, pharyngula, pre-hatch embryos, and hatched eleutheroembryos). GSHT concentration doubled between 12 hours post fertilization (hpf) and hatching. The GSH Eh increased, becoming more oxidizing during the first 12 h, and then oscillated around −190 mV through organogenesis, followed by a rapid change, associated with hatching, to a more negative (more reducing) Eh (−220 mV). After hatching, Eh stabilized and remained steady through 120 hpf. The dynamic changes in GSH redox status and concentration defined discrete windows of development: primary organogenesis, organ differentiation, and larval growth. We identified the set of zebrafish genes involved in the synthesis, utilization, and recycling of GSH, including several novel paralogs, and measured how expression of these genes changes during development. Ontogenic changes in the expression of GSH-related genes support the hypothesis that GSH redox state is tightly regulated early in development. This study

  18. Glutathione redox dynamics and expression of glutathione-related genes in the developing embryo.

    PubMed

    Timme-Laragy, Alicia R; Goldstone, Jared V; Imhoff, Barry R; Stegeman, John J; Hahn, Mark E; Hansen, Jason M

    2013-12-01

    Embryonic development involves dramatic changes in cell proliferation and differentiation that must be highly coordinated and tightly regulated. Cellular redox balance is critical for cell fate decisions, but it is susceptible to disruption by endogenous and exogenous sources of oxidative stress. The most abundant endogenous nonprotein antioxidant defense molecule is the tripeptide glutathione (γ-glutamylcysteinylglycine, GSH), but the ontogeny of GSH concentration and redox state during early life stages is poorly understood. Here, we describe the GSH redox dynamics during embryonic and early larval development (0-5 days postfertilization) in the zebrafish (Danio rerio), a model vertebrate embryo. We measured reduced and oxidized glutathione using HPLC and calculated the whole embryo total glutathione (GSHT) concentrations and redox potentials (Eh) over 0-120 h of zebrafish development (including mature oocytes, fertilization, midblastula transition, gastrulation, somitogenesis, pharyngula, prehatch embryos, and hatched eleutheroembryos). GSHT concentration doubled between 12h postfertilization (hpf) and hatching. The GSH Eh increased, becoming more oxidizing during the first 12h, and then oscillated around -190 mV through organogenesis, followed by a rapid change, associated with hatching, to a more negative (more reducing) Eh (-220 mV). After hatching, Eh stabilized and remained steady through 120 hpf. The dynamic changes in GSH redox status and concentration defined discrete windows of development: primary organogenesis, organ differentiation, and larval growth. We identified the set of zebrafish genes involved in the synthesis, utilization, and recycling of GSH, including several novel paralogs, and measured how expression of these genes changes during development. Ontogenic changes in the expression of GSH-related genes support the hypothesis that GSH redox state is tightly regulated early in development. This study provides a foundation for understanding

  19. 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.

  20. 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

  1. Azadirachta indica Attenuates Colonic Mucosal Damage in Experimental Colitis Induced by Trinitrobenzene Sulfonic Acid

    PubMed Central

    Gautam, M. K.; Goel, Shalini; Ghatule, R. R.; Singh, A.; Joshi, V. K.; Goel, R. K.

    2013-01-01

    Azadirachta indica leaves indicated the presence of active principles with proven antioxidants, antiinflammatory, immunomodulatory, free radical scavenging and healing properties. In the present study we evaluated the healing effects of 50% ethanol extract of dried leaves of Azadirachta indica on trinitrobenzene sulfonic acid-induced colitis in rats. Azadirachta indica extract (500 mg/kg) was administered orally, once daily for 14 days and studied for its effects on diarrhoea, food and water intake, body weight changes, colonic damage and inflammation, histology, antibacterial activity and free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and myeloperoxidase activities in colonic tissue. Intracolonic trinitrobenzene sulfonic acid increased colonic mucosal damage and inflammation, diarrhea, but decreased body weight which were reversed by Azadirachta indica extract and sulfasalazine (positive control) treatments. Azadirachta indica extract showed antibacterial activity. Azadirachta indica extract and sulfasalazine enhanced the antioxidants but decreased free radicals and myeloperoxidase activities affected in trinitrobenzene sulfonic acid-induced colitis. Azadirachta indica extract, thus seemed to be effective in healing trinitrobenzene sulfonic acid-induced colitis in rats. PMID:24403663

  2. Inhibition of Glutathione Biosynthesis Sensitizes Plasmodium berghei to Antifolates

    PubMed Central

    Koonyosying, Pongpisid; Uthaipibull, Chairat; Kamchonwongpaisan, Sumalee

    2016-01-01

    Glutathione plays a central role in maintaining cellular redox homeostasis, and modulations to this status may affect malaria parasite sensitivity to certain types of antimalarials. In this study, we demonstrate that inhibition of glutathione biosynthesis in the Plasmodium berghei ANKA strain through disruption of the γ-glutamylcysteine synthetase (γ-GCS) gene, which encodes the first and rate-limiting enzyme in the glutathione biosynthetic pathway, significantly sensitizes parasites in vivo to pyrimethamine and sulfadoxine, but not to chloroquine, artesunate, or primaquine, compared with control parasites containing the same pyrimethamine-resistant marker cassette. Treatment of mice infected with an antifolate-resistant P. berghei control line with a γ-GCS inhibitor, buthionine sulfoximine, could partially abrogate pyrimethamine and sulfadoxine resistance. The role of glutathione in modulating the malaria parasite's response to antifolates suggests that development of specific inhibitors against Plasmodium γ-GCS may offer a new approach to counter Plasmodium antifolate resistance. PMID:26953195

  3. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  4. Effect of glutathione during bottle storage of sparkling wine.

    PubMed

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

    2017-02-01

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

  5. N-->S phosphoryl migration in phosphoryl glutathion.

    PubMed

    Yang, H J; Liu, J; Zhao, Y F

    1993-07-01

    It was found that in the case of N-(diisopropylphosphoryl) glutathion (reduced form), 2, N-->S phosphoryl migration took place, but not for N,N-bis(diisopropylphosphoryl) glutathion (oxidized form) or N-diisopropylphosphoryl cysteine. These results were deduced by 31P-NMR tracing experiments. It was shown that phosphoryl migration was catalyzed by an intramolecular carboxyl group, and a mechanism involving a mixed carboxyl-phosphoric anhydride was proposed. A competitive reaction between the amino and thiol group toward diisopropyl phosphite indicated that the phospho-thiol derived from N-(diisopropylphosphoryl) glutathion (reduced form), 2, did not result from direct phosphorylation of the thiol group. N,S-Bis(diisopropylphosphoryl) glutathion provides an authentic sample to confirm the migrated phosphoryl thiol product.

  6. Mucosal immunoglobulins and B cells of teleost fish.

    PubMed

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

    2011-12-01

    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 naïve 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.

  7. 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

  8. 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

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

    PubMed Central

    Øverby, Anders; Stokland, Ragni A.; Åsberg, Signe E.; Sporsheim, Bjørnar; 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

  10. 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

  11. 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 20 g L(-1) glucose was fermented for 48 h; the fermentation liquid was passed through an UF membrane to remove macromolecules. Glutathione in this permeate was concentrated for 48 h to 545.1 ± 33.6 mg L(-1) using the NF membrane; this was a significantly higher concentration than that obtained with yeast extract peptone dextrose (YPD) medium following 96 h NF concentration (217.9 ± 57.4 mg L(-1)). This higher glutathione concentration results from lower cellular growth in SD medium (final OD600 = 6.9 ± 0.1) than in YPD medium (final OD600 = 11.0 ± 0.6) and thus higher production of extracellular glutathione (16.0 ± 1.3 compared to 9.2 ± 2.1 mg L(-1) in YPD medium, respectively). Similar fermentation and membrane processing of sweet sorghum juice containing 20 g L(-1) total sugars provided 240.3 ± 60.6 mg L(-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.

  12. Uterine glutathione reductase activity: modulation by estrogens and progesterone.

    PubMed

    Díaz-Flores, M; Baiza-Gutman, L A; Pedrón, N N; Hicks, J J

    1999-10-29

    The aim of this study was to determine whether glutathione reductase activity in uterine tissue is regulated by sex hormones. In spayed rats uterine glutathione reductase was significantly increased by exogenous estrogen (P< 0.01), progesterone (P< 0.01) or estrogen plus progesterone (P<0.01). When enzyme activity is expressed per mg protein, daily administration of estrogen or progesterone induces a progressive increase of this enzyme between 24 to 48 h or 24 to 72 h of treatment, respectively. Whereas the combination of both steroids causes an earlier and higher increase in glutathione reductase activity at 24 h of treatment. Estradiol singly or in combination with progesterone induced the highest protein concentration in the uterus. Whereas uterine DNA concentration is only significantly affected by estradiol. Our results suggest that uterine glutathione reductase is regulated by estradiol and progesterone and may be involved in maintaining levels of reduced glutathione in the uterus. This compound may be required for control of the redox state of thiol groups and in detoxification reactions involving H2O2 and electrophylic substances. The antioxidant action of estrogens is partially due to the stimulation of glutathione reductase.

  13. Dietary guidance and ileal enteroendocrine cells in patients with irritable bowel syndrome

    PubMed Central

    Mazzawi, Tarek; El-Salhy, Magdy

    2016-01-01

    The enteroendocrine cells of the ileum are stimulated by the luminal contents to release specific hormones that regulate its functions. The density of ileal enteroendocrine cells is abnormal in patients with irritable bowel syndrome (IBS), and the majority of patients with IBS associate their symptoms to the consumption of certain foodstuffs. The present study investigated the effect of dietary guidance on the enteroendocrine cells of the ileum in 11 patients with IBS. A total of 10 control subjects were also included. Each patient received three sessions of dietary guidance. Colonoscopies were performed on both controls and patients with IBS (at baseline and 3–9 months after the patients had received dietary guidance). Biopsy samples from the ileum were immunostained for all enteroendocrine cells and quantified by computerized image analysis. The densities of serotonin-immunoreactive cells in controls and in patients with IBS prior to and following dietary guidance were 35.5±5.7, 38.7±7.1 and 22.3±2.6 cells/mm2, respectively (mean ± standard error of the mean; P=0.046); the corresponding values for PYY-immunoreactive cells were 16.7±2.8, 20.2±5.1 and 21.3±2.7 cells/mm2 (P=0.86). These results suggest that changes in enteroendocrine cell densities in the ileum along with changes in enteroendocrine cells throughout the gastrointestinal tract may contribute to the improvement in IBS symptoms following dietary guidance. PMID:27588061

  14. Blockade of Central GLP-1 Receptors Deteriorates the Improvement of Diabetes after Ileal Transposition

    PubMed Central

    Chen, Weijie; Xu, Qianqian; Xiao, Yiding; Zhou, Jiaolin; Zhang, Weimin; Lin, Guole; Gong, Fengying

    2016-01-01

    Background: The mechanism of improvement of type 2 diabetes mellitus induced by ileal transposition (IT) is undefined. Our aim was to investigate the possible role of central glucagon-like peptide 1 (GLP-1) after IT. Methods: Ninety male diabetic rats were randomly divided into the IT, sham IT (S-IT) and control group. The food intake, glucose metabolism and GLP-1 level were measured. Subsequently, we administered GLP-1 antagonist via lateral brain ventricle cannula to block central GLP-1 receptor, and verified whether the food intake, glucose metabolism changed. And the activated pro-opiomelanocortin (POMC) neurons in different groups were compared after sacrifice. Results: IT induced significant diabetic improvement with decreased maximum food intake and higher postprandial GLP-1 level. The GLP-1 level in cerebrospinal fluid increased in correlation with the plasma GLP-1 level. When the central GLP-1 receptor antagonist was given to the IT group rats, the improvement of the glucose level declined. The glucose level surged (169.9 ± 14.2) % during the oral glucose tolerance test, the range was larger than that before central blockade ((67.1 ± 14.2) %, P < 0.001). Moreover, the POMC neuron number in the arcuate nucleus of the hypothalamus were reduced (12.7 ± 6.1 at a magnification of 100×). The relative content level of POMC-derived peptides in the pituitary was lower (0.1 ± 0.05). Conclusions: The central GLP-1 might play an important role in the remission of diabetes after IT. POMC neurons in the hypothalamus may be activated by the enhanced level of GLP-1 after IT. PMID:27994501

  15. Ondansetron: A newer aspect of dose response relationship on ileal smooth muscles of rabbit.

    PubMed

    Afzal, Ayesha; Khan, Bushra Tayyaba; Bakhtiar, Salman

    2016-01-01

    There are several life threatening deadly diseases in our world but ‘Cancer’ out powers them all in recent years. Chemotherapy may be used on its own or an adjunct to other forms of therapy. Despite the advancement in cytotoxic drug therapy and supportive treatment almost 70% of patient suffer from chemotherapy induced nausea and vomiting (CINV). Ondansetron, a 5-HT(3) receptor antagonist has now become a gold standard in the treatment of chemotherapy induced nausea and vomiting. The central actions of ondansetron are well established but its peripheral actions are not well recognized. The aim of our study was to explore the peripheral actions of ondansetron. Experiments were performed in five groups (n=6) and ileal smooth muscles activity was recorded on power lab (USA). The effects of increasing concentrations of acetylcholine, serotonin & ondansetron alone was observed in first three groups. In the next two groups effects of acetylcholine and serotonin pretreated with fixed concentration (1ml) of ondansetron (10¯ϖ M)were studied. The maximum response obtained by acetylcholine served as a control for our study. Maximum response with acetylcholine was taken as 100% and with serotonin was 177 percent of control. Cumulative dose response curve with ondansetron was triphasic. At 10¯ψM it was 28.8%, whereas with 10¯ξM the amplitude decreased to 16.87%, it reached to plateau at 10¯ϖ M. Response of acetylcholine & serotonin was decreased to 57% and 78% respectively in the presence of fixed concentration of ondansetron (10¯ϖ M). Ondansetron reduces the acetylcholine and serotonin induced gastrointestinal motility. Our study has indicated that ondansetron apart from having central action also has marked peripheral actions that play an important role in CINV and may act as a partial agonist.

  16. 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 < 0.05) than in the pigs fed white or yellow maize. Energy digestibility (P < 0.001) and metabolizability (P < 0.01) were higher in the pigs fed the white and yellow maize diets than in those fed the QPM diets. The AID of lysine was higher (P < 0.01) in the QPM diets than in the white and yellow maize. The AIDs of leucine, isoleucine, valine, phenylalanine, and methionine were lower in the QPM diets than those of maize (white and yellow) (all P < 0.05). Maize (white and yellow) had greater SIDs of leucine, isoleucine, valine, phenylalanine, glutamic acid, serine, alanine, tyrosine, and proline (P < 0.05). Conclusions Based on these results, it was concluded that QPM had a lower metabolizable energy content and a higher amount of digestible lysine than normal maize. PMID:25045520

  17. Body and intestinal growth of broiler chicks on a commercial starter diet. 1. Intestinal weight and mucosal development.

    PubMed

    Iji, P A; Saki, A; Tivey, D R

    2001-09-01

    1. A study was conducted on the pattern of development of the intestinal mucosa of the Steggles x Ross (F1) strain of broiler chickens reared on a commercial starter diet. The mechanisms underlying the structural changes were also assessed. 2. In relation to body weight, small intestinal weight peaked at 7 d of age and declined subsequently. There was also a reduction in the relative weights of the gizzard and yolk sac with age. The length of the small intestine and its regions increased with age. 3. Crypt depth increased with age in the duodenum and jejunum while villus height increased significantly with age in all three regions of the small intestine. There were also significant changes in apparent villus surface area in the three regions, while interactions between age and intestinal region were significant in the case of crypt depth and villus height. 4. There were significant differences between the age groups in the mucosal protein content of jejunal and ileal homogenates, both tending to peak at 7 d of age. The DNA content of the intestinal mucosa declined with age in the three regions of the small intestine. While there was an increase in RNA content in the duodenum and ileum, there was a reduction in the jejunum. 5. Protein: DNA ratio increased between hatch and 21 d of age in all intestinal regions. Protein: RNA ratio decreased with age in the duodenum and ileum but increased in the jejunum. There were significant increases in RNA: DNA ratio in the duodenum and ileum but no changes were observed in the jejunum. The interactions between age and intestinal region were significant for all biochemical indices assessed. 6. At all ages, enterocyte proliferation at the jejunum was completed and quantifiable within 1 h of administration of 5-bromo-2'-deoxyuridine (BrDU). Subsequent assessment revealed an increase in crypt column count and number of BrDU-labelled cells. The rate of cell migration increased with age while there was a decline in the distance

  18. Oleic acid-induced mucosal injury in developing piglet intestine.

    PubMed

    Velasquez, O R; Henninger, K; Fowler, M; Tso, P; Crissinger, K D

    1993-03-01

    A role for luminal nutrients, in particular products of lipid digestion, in the pathogenesis of mucosal injury to developing intestine has been postulated. We evaluated changes in mucosal permeability and light and electron microscopic histology induced by luminal perfusion with the long-chain fatty acid oleate in developing piglet intestine as a function of age and concentration of the fatty acid. 51Cr-labeled EDTA plasma-to-lumen clearance was measured in jejunum and ileum of 1-day-, 3-day-, 2-wk-, and 1-mo-old piglets during sequential perfusion with saline control (20 min); 0, 1, 5, and 10 mM oleic acid/10 mM taurocholate in saline (20 min); and normal saline (60 min). The jejunum of piglets < or = 2 wk showed significantly greater increases in mucosal permeability compared with 1-mo-old animals after perfusion with oleic acid. This effect was dependent on the luminal concentration of the fatty acid and was associated with mucosal injury evident under light and electron microscopy. In contrast, the overall response in ileum was more attenuated compared with jejunum. Thus oleic acid, a common dietary fatty acid, induces dose- and age-dependent injury in developing piglet intestine. Investigation of the mechanisms of this injury may provide the basis for dietary modifications directed at decreasing the risk of mucosal injury during enteral feeding in neonatal intestine.

  19. Mucosal mast cells and developmental changes in gastric absorption.

    PubMed

    Catto-Smith, A G; Ripper, J L

    1995-01-01

    We aimed to establish whether gastric mucosal mast cells undergo degranulation during normal postnatal development and to correlate this with gastric electrical parameters, paracellular permeability, and macromolecular absorption. Sprague-Dawley rats were studied between 10 and 30 days after birth. Gastric mucosal mast cell degranulation occurred and was maximal on days 15 and 17, measured by histology and gastric and serum levels of rat mast cell protease II. Short-circuit current, transepithelial conductance, and permeability of voltage-clamped glandular stomach were elevated in younger animals, falling with age except for a transient but significant increase in conductance and permeability at 17 days, closely correlated with maximal mast cell degranulation. Macromolecular uptake was significantly increased in animals aged 10-15 days. Concanavalin A and antigen-induced mast cell degranulation increased conductance and permeability in vitro in younger animals. We conclude that 1) gastric mucosal mast cells degranulate during development, 2) the neonatal stomach has increased permeability and uptake of macromolecules, and 3) gastric mucosal mast cell degranulation during development may affect mucosal permeability.

  20. Management of a large mucosal defect after duodenal endoscopic resection

    PubMed Central

    Fujihara, Shintaro; Mori, Hirohito; Kobara, Hideki; Nishiyama, Noriko; Matsunaga, Tae; Ayaki, Maki; Yachida, Tatsuo; Masaki, Tsutomu

    2016-01-01

    Duodenal endoscopic resection is the most difficult type of endoscopic treatment in the gastrointestinal tract (GI) and is technically challenging because of anatomical specificities. In addition to these technical difficulties, this procedure is associated with a significantly higher rate of complication than endoscopic treatment in other parts of the GI tract. Postoperative delayed perforation and bleeding are hazardous complications, and emergency surgical intervention is sometimes required. Therefore, it is urgently necessary to establish a management protocol for preventing serious complications. For instance, the prophylactic closure of large mucosal defects after endoscopic resection may reduce the risk of hazardous complications. However, the size of mucosal defects after endoscopic submucosal dissection (ESD) is relatively large compared with the size after endoscopic mucosal resection, making it impossible to achieve complete closure using only conventional clips. The over-the-scope clip and polyglycolic acid sheets with fibrin gel make it possible to close large mucosal defects after duodenal ESD. In addition to the combination of laparoscopic surgery and endoscopic resection, endoscopic full-thickness resection holds therapeutic potential for difficult duodenal lesions and may overcome the disadvantages of endoscopic resection in the near future. This review aims to summarize the complications and closure techniques of large mucosal defects and to highlight some directions for management after duodenal endoscopic treatment. PMID:27547003

  1. 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. PMID:26929697

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

    PubMed Central

    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

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

    PubMed Central

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

    2012-01-01

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

  4. Standardized ileal amino acid digestibility of meat and bone meal and soybean meal in laying hens and broilers.

    PubMed

    Adedokun, S A; Jaynes, P; Abd El-Hack, M E; Payne, R L; Applegate, T J

    2014-02-01

    The objective of this study was to determine the standardized ileal amino acid digestibility (SIAAD) of 7 meat and bone meal (MBM) and 3 soybean meal (SBM) samples in broilers (Ross 708) and laying hens (Hy-line W36). All 10 feed ingredients were evaluated in 21-d-old broiler chickens and 30- or 50-wk-old laying hens. Standardization was accomplished by correcting for basal ileal endogenous amino acid losses using a nitrogen-free diet. Broilers were reared in cages from d 0 to 16 on a standard broiler starter diet adequate in all nutrients and energy; thereafter, they were allotted to treatments using a randomized complete design with 6 replicate cages of 8 birds each. For the laying hens, 6 replicate cages of 6 birds each (542 cm(2)/bird) were used. Each treatment diet, which was fed for 5 d, was semipurified, with MBM or SBM being the sole source of amino acids in each diet. Ileal endogenous amino acid losses were not different between broilers and the 2 groups of laying hens. Meat and bone meal from different locations varied widely in digestibility. Broilers had higher (P < 0.05) SIAAD in 4 of the 7 MBM samples. In 2 of the 3 SBM samples, broilers had higher (P < 0.05) SIAAD for most of the nonessential amino acids. Generally, hens had 6.4 and 7.7% units less Met and Lys digestibility of all MBM samples after standardization. Dry matter digestibility values of the SBM samples were higher (P < 0.05) in broilers. Likewise, broilers had 4.1 and 1.5% units more Met and Lys digestibility of all the SBM samples evaluated compared with those from laying hens. The results of these experiments suggest that differences exist in the digestive capabilities of laying hens and broilers, which indicates that species-specific nutrient digestibility values or adjustments may be needed.

  5. 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.

  6. Composition of Ileal Bacterial Community in Grazing Goats Varies across Non-rumination, Transition and Rumination Stages of Life

    PubMed Central

    Jiao, Jinzhen; Wu, Jian; Zhou, Chuanshe; Tang, Shaoxun; Wang, Min; Tan, Zhiliang

    2016-01-01

    The establishment of gut microbiota is increasingly recognized as a crucial action in neonatal development, host health and productivity. We hypothesized that the ileal microbiome shifted as goats matured, and this colonization process would be associated with host fermentation capacity. To this end, 18 Liuyang black grazing goats were randomly slaughtered at d 0, 7, 28, 42, and 70. Ileal microbiota was profiled by Miseq sequencing of 16S rRNA gene of bacteria, and fermentation capacity [volatile fatty acid, activities of amylase, carboxymethylcellulase (CMCase) and xylanase] was determined using digesta sample. Principal coordinate analysis revealed that each age group harbored its distinct bacteria. Total bacteria copy number and most alpha diversity indexes increased (P < 0.01) from d 0 to 70. At the phylum level, abundances of Cyanobacteria (P = 0.018) and TM7 (P = 0.010) increased linearly, abundances of Bacteroidetes (P = 0.075) and Fibrobacteres (P = 0.076) tended to increase linearly, whist Proteobacteria abundance tended to decline quadratically (P = 0.052) with age. At the genus level, Enterococcus (30.9%), Lactobacillus (32.8%), and Escherichia (2.0%) dominated at d 0, while Prevotella, Butyrivibrio, Ruminococcus, SMB53, and Fibrobacter surged in abundance after day 20. The highest amylase activity was observed at day 42, while xylanase activity increased quadratically (P = 0.002) from days 28 to 70. Correlation analysis indicated that abundances of Bacteroides, Clostridium, Lactobacillus, Propionibacterium, Enterococcus, and p-75-a5 positively correlated with enzyme activity. Collectively, ileal bacteria in grazing goats assemble into distinct communities throughout development, and might participate in the improvement of host fermentation capacity. PMID:27656165

  7. Effect of oral glutamine administration on bacterial tanslocation, endotoxemia, liver and ileal morphology, and apoptosis in rats with obstructive jaundice.

    PubMed

    Margaritis, Vassilios G; Filos, Kriton S; Michalaki, Marina A; Scopa, Chrisoula D; Spiliopoulou, Iris; Nikolopoulou, Vassiliki N; Vagianos, Constantine E

    2005-10-01

    Postoperative complications in patients with obstructive jaundice remain increased when associated with endotoxemia and the inflammatory response due to gut barrier failure. Administration of glutamine has been proposed to maintain the integrity of the gut mucosa and thus reduce bacterial translocation (BT), but the effects of this pretreatment on apoptosis and histologic morphology of various organs affected by BT in obstructive jaundice have not been studied. We therefore studied the effects of oral glutamine supplementation on endotoxemia, BT, liver and terminal ileal morphology, and apoptosis in an experimental model of obstructive jaundice. A total of 60 male Wistar rats were randomly divided into four groups of 15 each: I, controls; II, sham-operated; III, bile duct ligation (BDL); IV, BDL + glutamine (4.5 g/kg/day in drinking water). Ileal samples for histology, DNA and protein content, liver biopsies, mesenteric lymph nodes (MLNs) for culture, and portal and systemic blood samples for endotoxin measurements were obtained 10 days later. Compared to the controls, a significant increase in contaminated MLN and liver samples and increased endotoxemia were noted in group III (p < 0.01) but were significantly reduced in group IV (p < 0.05). Group IV also had a significantly higher number of mitoses per crypt (M/c) (p < 0.05), less apoptotic body counts (ABCs) (p < 0.05), and a higher DNA content than did group III (p < 0.05). Liver biopsies from group III displayed typical changes of large duct obstruction that significantly improved after glutamine treatment, with decreased ductular proliferation. We concluded that supplementation of oral glutamine in the presence of obstructive jaundice ameliorates BT, endotoxemia, and apoptosis and improves the ileal and liver histology.

  8. The effect of condensed tannins from heated and unheated cottonseed on the ileal digestibility of amino acids for the growing rat and pig.

    PubMed

    Yu, F; Moughan, P J; Barry, T N; McNabb, W C

    1996-09-01

    The effect of condensed tannins (CT) from heated and unheated cottonseed on the apparent ileal digestibility of amino acids for the growing rat and pig was determined. In Expt 1, twenty-four rats were allocated to four semi-purified diets which contained cottonseed kernel and hulls as the only protein source. Two of the diets contained unheated solvent-extracted cottonseed kernel and hulls, while the remaining two diets contained similar material but which had been heat-treated by autoclaving at 110 degrees for 120 min. In Expt 2, twelve rats and twelve pigs were fed on four semi-purified diets containing commercial cottonseed meal (CSM) as the only protein source. Cr2O3 was added to all diets as an indigestible marker. For each pair of diets in both experiments, PEG was either included or excluded. The effect of CT was assessed by comparing control animals (-PEG; CT acting) with PEG-supplemented animals (+PEG; CT inactivated). Ileal contents from the terminal 150 and 450 mm of ileum were collected at slaughter, 7 h from the start of feeding, for the rats and pigs respectively. Apparent ileal amino acid digestibility for rats fed on the diet containing cottonseed kernel and hulls was significantly depressed by the heat treatment, particularly for lysine and threonine. On average, apparent ileal amino acid digestibility in the diets without PEG was decreased from 0.80 to 0.70 by heat treatment. Dietary cottonseed CT depressed apparent ileal protein digestibility in the pig and in the rat. The addition of PEG to the diets significantly increased the apparent ileal digestibility of N and some amino acids for the pigs and the rats. The mean increase in apparent ileal digestibility due to PEG addition for the fourteen amino acids was 2 percentage units in both species fed on the commercial CSM diets, and 2 or 4 percentage units in rats fed on the unheated or the heated cottonseed kernel and hull diets respectively. The effect of PEG was similar in the heated and

  9. The mouse ileal lipid-binding protein gene: a model for studying axial patterning during gut morphogenesis

    PubMed Central

    1994-01-01

    Normal, chimeric-transgenic, and transgenic mice have been used to study the axial patterns of ileal lipid-binding protein gene (Ilbp) expression during and after completion of gut morphogenesis. Ilbp is initially activated in enterocytes in bidirectional wave that expands proximally in the ileum and distally to the colon during late gestation and the first postnatal week. This activation occurs at the same time that a wave of cytodifferentiation of the gut endoderm is completing its unidirectional journey from duodenum to colon. The subsequent contraction of Ilbp's expression domain, followed by its reexpansion from the distal to proximal ileum, coincides with a critical period in gut morphogenesis (postnatal days 7-28) when its proliferative units (crypts) form, establish their final stem cell hierarchy, and then multiply through fission. The wave of reactivation is characterized by changing patterns of Ilbp expression: (a) at the proximal most boundary of the wave, villi contain a mixed population of scattered ileal lipid- binding protein (ILBP)-positive and ILBP-negative enterocytes derived from the same monoclonal crypt; (b) somewhat more distally, villi contain vertical coherent stripes of wholly ILBP-positive enterocytes derived from monoclonal crypts and adjacent, wholly ILBP-negative stripes of enterocytes emanating from other monoclonal crypts; and (c) more distally, all the enterocytes on a villus support Ilbp expression. Functional mapping studies of Ilbp's promoter in transgenic mice indicate that nucleotides -145 to +48 contain cis-acting elements sufficient to produce an appropriately directed distal-to-proximal wave of Ilbp activation in the ileum, to maintain an appropriate axial distribution of monophenotypic wholly reporter-positive villi in the distal portion of the ileum, as well as striped and speckled villi in the proximal portion of its expression domain, and to correctly support reporter production in villus-associated ileal enterocytes

  10. Monomer and linkage type of galacto-oligosaccharides affect their resistance to ileal digestion and prebiotic properties in rats.

    PubMed

    Hernández-Hernández, Oswaldo; Marín-Manzano, M Carmen; Rubio, Luis A; Moreno, F Javier; Sanz, M Luz; Clemente, Alfonso

    2012-07-01

    A detailed study was performed to compare the in vivo ileal digestibility and modulatory effects in fecal microbiota of novel galacto-oligosaccharides (GOS) derived from lactulose [GOS-Lu; degree of polymerization (DP) ≥2, 14.0% trisaccharides] and commercial GOS derived from lactose (GOS-La; DP ≥3, 35.1% trisaccharides) in growing rats (5 wk old). Rats were fed either a control diet or diets containing 1% (wt:wt) of GOS-Lu or GOS-La for 14 d. Quantitative analysis of carbohydrates from dietary and ileal samples demonstrated that the trisaccharide fraction of GOS-Lu was significantly more resistant to gut digestion than that from GOS-La, as indicated by their ileal digestibility rates of 12.5 ± 2.6% and 52.9 ± 2.7%, respectively, whereas the disaccharide fraction of GOS-Lu was fully resistant to the extreme environment of the upper digestive tract. The low ileal digestibility of GOS-Lu was due to the great resistance of galactosyl-fructoses to mammalian digestive enzymes, highlighting the key role played by the monomer type and linkage involved in the oligosaccharide chain. The partial digestion of GOS-La trisaccharides showed that glycosidic linkages (1→6) and (1→2) between galactose and glucose monomers were significantly more resistant to in vivo gastrointestinal digestion than the linkage (1→4) between galactose units. The absence of GOS-La and GOS-Lu digestion-resistant oligosaccharides in fecal samples indicated that they were readily fermented within the large intestine, enabling both types of GOS to have a potential prebiotic function. Indeed, compared with controls, the GOS-Lu group had significantly more bifidobacteria in fecal samples after 14 d of treatment. The number of Eubacterium rectale also was greater in the GOS-Lu and GOS-La groups than in controls. These novel data support a direct relationship between patterns of resistance to digestion and prebiotic properties of GOS.

  11. The effect of microbial phytase on true and apparent ileal amino acid digestibilities in growing-finishing pigs.

    PubMed

    Pomar, C; Gagné, F; Matte, J J; Barnett, G; Jondreville, C

    2008-07-01

    Ten 56-d-old, 15-kg barrows were surgically fitted with a postvalvular T-cecum cannula at the ileo-cecal junction to evaluate the effect of microbial phytase on apparent and true ileal AA digestibility and N utilization. A semipurified cornstarch- and soybean meal-based diet was formulated to contain 3.4 Mcal of DE/kg, 17.0% CP, 0.8% Ca, and 0.6% P but had a low phytate-P concentration (0.13%; all on an as-fed basis). Chromic oxide and dysprosium chloride were used as indigestible markers. The basal diet was supplemented with 0 or 1,000 phytase units/kg of microbial phytase. Postprandial plasma urea N and alpha-amino N concentrations, excretion of Ca, P, and N in feces and urine, and ileal AA digestibilities were determined 3 times at 4-wk intervals beginning at 70 d of age. The homoarginine (HA) method was used to determine endogenous AA flow by replacing 50% of the basal protein with guanidinated protein. Microbial phytase had no effect on apparent ileal digestibility (AID) or on true ileal digestibilities of N and most AA but did increase AID for arginine (P = 0.006) and methionine (P = 0.037). However, in HA diets, phytase increased the AID of CP (P = 0.01) and several AA. Addition of microbial phytase had no effect on the postprandial alpha-amino N concentrations in plasma but increased overall plasma urea N concentrations (P = 0.035). Barrows fed phytase-supplemented diets had decreased P in feces (P = 0.003) and greater P in urine (P = 0.001) but comparable total P excretion compared with barrows fed no phytase-supplemented diets. In conclusion, the addition of phytase to a semi-purified soybean meal-based diet did not affect the AID of several AA. In addition, differences between the basal and HA diets in N digestibilities indicated that that guanidination may limit the use of the HA method in determining endogenous protein losses.

  12. Influence of limestone and phytase on broiler performance, gastrointestinal pH, and apparent ileal nutrient digestibility.

    PubMed

    Walk, C L; Bedford, M R; McElroy, A P

    2012-06-01

    An experiment was conducted to determine the influence of 2 levels of dietary Ca from limestone and 3 levels of phytase on broiler performance, bone ash, gastrointestinal pH, and apparent ileal digestibility (AID) of Ca, P, and amino acids. Cobb 500 broilers (n = 576) were allowed access to one of 6 corn-soy diets from 0 to 16 d. Experimental diets contained 1.03% or 0.64% Ca from limestone and 0.61% total P. Each diet was supplemented with 0, 500, or 5,000 FTU/kg of phytase to create a 2 × 3 factorial experiment. Broiler feed intake (FI) and BW gain were not affected by dietary Ca or phytase. Feed conversion ratio was improved (P < 0.05) as dietary phytase increased (1.36, 1.34, and 1.31, respectively). Tibia ash percent was reduced (P < 0.05) from 41.4 to 40.0% as dietary Ca decreased but increased with phytase addition (P < 0.05). Gizzard and ileal pH were reduced (P < 0.05) in broilers fed 0.64% Ca compared with broilers fed 1.03% Ca. Phytase at 5,000 FTU/kg increased (P < 0.05) pH in the gizzard, duodenum, jejunum, and ileum. Apparent ileal P digestibility was increased (P < 0.05) in broilers fed 0.64% Ca compared with broilers fed 1.03% Ca (0.68 vs. 0.73, respectively). Apparent ileal Ca digestibility was increased (P < 0.05) in broilers fed 1.03% Ca compared with broilers fed 0.64% Ca (0.67 vs. 0.53, respectively). Phytase improved AID of CP in broilers fed 1.0% Ca but did not have an effect on AID of CP in broilers fed 0.64% Ca, which resulted in a Ca × phytase interaction (P < 0.05). In conclusion, high dietary Ca increased pH in gizzard and ileum and interfered with the AID of P and CP. The interactions between Ca and phytase in the gastrointestinal tract are complex, and feeding phytase at doses above industry recommendations may allow for reduced-Ca diets while maintaining broiler performance, bone ash, and improving amino acid digestibility.

  13. Segmental absence of intestinal muscle with ileal web in an extremely low birth weight infant: case report.

    PubMed

    Buyuktiryaki, Mehmet; Kanmaz, Hayriye G; Okur, Nilüfer; Ates, Ufuk; Sirvan, Ali L; Uras, Nurdan

    2016-04-01

    Spontaneous intestinal perforations are localized perforations without the typical clinical, radiological, and histopathological features of necrotizing enterocolitis. Spontaneous intestinal perforation is a recently defined clinical entity. The best-known risk factor is prematurity. It is seen 2-3% in very low birthweight infants and 5 % of extremely low birthweight infants. Herein we report an extremely low birthweight infant with spontaneous intestinal perforation, segmental absence of intestinal muscle and an ileal web as an underlying cause. We aimed to draw attention to the segmental absence of intestinal muscle which is rare but increasingly reported cause of spontaneous intestinal perforation and the importance of histopathologic examination of surgical specimens.

  14. 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

    Røkke, Ola; Iversen, Knut; Olsen, Torill; Ristesund, Sølvi-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 (1–15) 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

  15. 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.

  16. 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.

  17. Immunomodulation by mucosal gene transfer using TGF-beta DNA.

    PubMed Central

    Kuklin, N A; Daheshia, M; Chun, S; Rouse, B T

    1998-01-01

    This report evaluates the efficacy of DNA encoding TGF-beta administered mucosally to suppress immunity and modulate the immunoinflammatory response to herpes simplex virus (HSV) infection. A single intranasal administration of an eukaryotic expression vector encoding TGF-beta1 led to expression in the lung and lymphoid tissue. T cell-mediated immune responses to HSV infection were suppressed with this effect persisting as measured by the delayed-type hypersensitivity reaction for at least 7 wk. Treated animals were more susceptible to systemic infection with HSV. Multiple prophylactic mucosal administrations of TGF-beta DNA also suppressed the severity of ocular lesions caused by HSV infection, although no effects on this immunoinflammatory response were evident after therapeutic treatment with TGF-beta DNA. Our results demonstrate that the direct mucosal gene transfer of immunomodulatory cytokines provides a convenient means of modulating immunity and influencing the expression of inflammatory disorders. PMID:9664086

  18. Potential Benefits of Oral Cryotherapy for Chemotherapy-Induced Mucositis.

    PubMed

    Wodzinski, Amelia

    2016-10-01

    Mucositis is a common side effect of cancer therapies that causes painful, erythematous lesions to develop in the gastrointestinal tract. These lesions can lead to malnutrition, increased risk for serious infection, prolonged hospital stays, and reduced quality of life. Oral cryotherapy, or the use of ice chips to cool the mucous membranes during bolus chemotherapy infusions (e.g., 5-fluorouracil [Adrucil®] and melphalan [Alkeran®]), is the most readily accessible and cost-effective intervention available. Although many factors may contribute to the development of mucositis during cancer treatment, studies have found a reduction in the incidence and the severity of mucositis with the use of oral cryotherapy.


  19. 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 β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. 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.

  20. 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.

  1. Hepatic glutathione and glutathione S-transferase in selenium deficiency and toxicity in the chick

    SciTech Connect

    Kim, Y. S.

    1989-01-01

    First, the hepatic activity of GSH-T{sub CDNB} was increased only under conditions of severe oxidative stress produced by combined Se- and vitamin E (VE)-deficiency, indicating that VE also affects GSH metabolism. Second, the incorporation of {sup 35}S-methionine into GSH and protein was about 4- and 2-fold higher, respectively, in Se- and VE-deficient chick hepatocytes as compared to controls. Third, chicks injected with the glutathione peroxidase (SeGSHpx) inhibitor, aurothioglucose (AuTG), showed increase hepatic GSH-T{sub CDNB} activity and plasma GSH concentration regardless of their Se status. Fourth, the effect of ascorbic acid (AA), on GSH metabolism was studied. Chicks fed 1000 ppm AA showed decreased hepatic GSH concentration compared to chicks fed no AA in a Se- and VE-deficient diet. Fifth, chicks fed excess Se showed increase hepatic activity of GSH-T{sub CDNB} and GSH concentration regardless of VE status.

  2. 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 (0–100) 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 vestibule’s 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

  3. Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

    SciTech Connect

    Watkins, E.B.; Findlay, P.; Gelmann, E.; Lane, H.C.; Zabell, A.

    1987-09-01

    The oropharynx and hypopharynx are common sites of involvement in AIDS patients with mucocutaneous Kaposi's sarcoma. The radiotherapist is often asked to intervene with these patients due to problems with pain, difficulty in swallowing, or impending airway obstruction. We have noted an unexpected decrease in normal tissue tolerance of the oropharyngeal mucosa to irradiation in AIDS patients treated in our department. Data on 12 patients with AIDS and Kaposi's sarcoma receiving oropharyngeal irradiation are presented here. Doses ranged from 1000 cGy to 1800 cGy delivered in 150-300 cGy fractions. Seven of eight patients receiving doses of 1200 cGy or more developed some degree of mucositis, four of these developed mucositis severe enough to require termination of treatment. All patients in this study received some form of systemic therapy during the course of their disease, but no influence on mucosal response to irradiation was noted. Four patients received total body skin electron treatments, but no effect on degree of mucositis was seen. Presence or absence of oral candidiasis was not an obvious factor in the radiation response of the oral mucosa in these patients. T4 counts were done on 9 of the 12 patients. Although the timing of the T4 counts was quite variable, no correlation with immune status and degree of mucositis was found. The degree of mucositis seen in these patients occurred at doses much lower than expected based on normal tissue tolerances seen in other patient populations receiving head and neck irradiations. We believe that the ability of the oral mucosa to repair radiation damage is somehow altered in patients with AIDS.

  4. Oral cryotherapy reduced oral mucositis in patients having cancer treatments.

    PubMed

    Spivakovsky, Sylvia

    2016-09-01

    Data sourcesCochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CANCERLIT, CINAHL, the US National Institutes of Health Trials Registry and the WHO Clinical Trials Registry Platform.Study selectionRandomised controlled trials (RCTs) assessing the effects of oral cryotherapy in patients with cancer receiving treatment compared to usual care, no treatment or other interventions to prevent mucositis. The primary outcome was incidence of mucositis and its severity.Data extraction and synthesisTwo reviewers carried out study assessment and data extraction independently. Treatment effect for continuous data was calculated using mean values and standard deviations and expressed as mean difference (MD) and 95% confidence interval. Risk ratio (RR) was calculated for dichotomous data. Meta-analysis was performed.ResultsFourteen studies with 1280 participants were included. Subgroup analysis was undertaken according to the main cancer treatment type. Cryotherapy reduced the risk of developing mucositis by 39% (RR = 0.61; 95%CI, 0.52 to 0.72) on patients treated with fluorouracil (5FU). For melphalan-based treatment the risk of developing mucositis was reduced by 41% (RR =0.59; 95%CI, 0.35 to 1.01). Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, numbness/taste disturbance and tooth pain. This appears to contribute to the high rates of compliance seen in the included studies.ConclusionsThere is confidence that oral cryotherapy leads to a large reduction in oral mucositis in adults treated with 5FU. Although there is less certainty on the size of the reduction on patients treated with melphalan, it is certain there is reduction of severe mucositis.

  5. 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.

  6. Targeting early infection to prevent HIV-1 mucosal transmission.

    PubMed

    Haase, Ashley T

    2010-03-11

    Measures to prevent sexual mucosal transmission of human immunodeficiency virus (HIV)-1 are urgently needed to curb the growth of the acquired immunodeficiency syndrome (AIDS) pandemic and ultimately bring it to an end. Studies in animal models and acute HIV-1 infection reviewed here reveal potential viral vulnerabilities at the mucosal portal of entry in the earliest stages of infection that might be most effectively targeted by vaccines and microbicides, thereby preventing acquisition and averting systemic infection, CD4 T-cell depletion and pathologies that otherwise rapidly ensue.

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

    PubMed Central

    Sold, Moritz; Kähler, 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

  8. A case of unexpected regeneration of small intestinal mucosal necrosis.

    PubMed

    Kim, Dong Wook; Park, Youn Joon

    2012-01-01

    If full-thickness mucosa, including the mucosal crypt, has been almost denuded, mucosa cannot regenerate as has been shown by animal models. The authors experienced an unusual mucosal regeneration exceed denuded bowel that occur in midgut volvulus of duration 2 days in a 6-day-old infant. Santulli's jejunostomy was performed using seriously denuded small bowel to prevent short bowel syndrome, despite the risks of leakage or stricture. Subsequently, stomal mucosa was fully regenerated when grossly identified 19 days after the second operation without any surgical complications.

  9. Impact of dose and volume on radiation-induced mucositis.

    PubMed

    Mantini, Giovanna; Manfrida, Stefania; Cellini, Francesco; Giammarino, Daniela; Petrone, Adelina; Vitucci, Pasquale; Cellini, Numa

    2005-01-01

    There is a relationship between a given radiation dose and the resulting biological effect in the management of head and neck cancer. Radiation mucositis represents a frequent complication in cancer chemoradiation. Its prevention and treatment are major goals in radiation therapy schedules. Critical tissues can be spared using high conformal radiation therapy (3DCRT) based on consensus guidelines for target volume. Current approaches to radiation mucositis with respect to the dose and volume impact are illustrated. The monitoring system of late toxicity used by the authors is presented.

  10. Metabolic synthesis of clickable glutathione for chemoselective detection of glutathionylation.

    PubMed

    Samarasinghe, Kusal T G; Munkanatta Godage, Dhanushka N P; VanHecke, Garrett C; Ahn, Young-Hoon

    2014-08-20

    Glutathionylation involves reversible protein cysteine modification that regulates the function of numerous proteins in response to redox stimuli, thereby altering cellular processes. Herein we developed a selective and versatile approach to identifying glutathionylation by using a mutant of glutathione synthetase (GS). GS wild-type catalyzes coupling of γGlu-Cys to Gly to form glutathione. We generated a GS mutant that catalyzes azido-Ala in place of Gly with high catalytic efficiency and selectivity. Transfection of this GS mutant (F152A/S151G) and incubation of azido-Ala in cells efficiently afford the azide-containing glutathione derivative, γGlu-Cys-azido-Ala. Upon H2O2 treatment, clickable glutathione allowed for selective and sensitive detection of glutathionylated proteins by Western blotting or fluorescence after click reaction with biotin-alkyne or rhodamine-alkyne. This approach affords the efficient metabolic tagging of intracellular glutathione with small clickable functionality, providing a versatile handle for characterizing glutathionylation.

  11. 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.

  12. Feasible Relation between Glutathione Peroxidase and Febrile Seizure

    PubMed Central

    MAHYAR, Abolfazl; AYAZI, Parviz; DALIRANI, Reza; MOHAMMAD HOSEINI, Behzad; SAROOKHANI, Mohammad Reza; JAVADI, Amir; ESMAEILY, Shiva

    2017-01-01

    Objective We aimed to determine the relationship between serum glutathione peroxidase and febrile seizure. Materials & Methods In this case-control study, 43 children with simple febrile seizure (case group) were compared with 43 febrile children without seizure (control group) in terms of serum glutathione peroxidase level, measured by ELISA method. This study was conducted in Qazvin Children Hospital, Qazvin University of Medical Sciences in Qazvin, Iran in 2012-2013. The results were analyzed and compared in two groups. Results From 43 children 24 (53%) were male and 19 (47%) were female in children with simple febrile seizure, and 26 (60%) were male and 17 (40%) were female in febrile children without seizure (control group) (P=0.827). Serum glutathione peroxidase level was 166 U/ml (SD=107) in the case group and 141 U/ml (SD=90.5) in the control group of no significant difference. Conclusion There was no significant relationship between serum glutathione peroxidase and simple febrile seizure. Thus, it seems that glutathione peroxidase, an essential component of antioxidant system, does not play any role in the pathogenesis of simple febrile seizure. PMID:28277558

  13. Gastric invasion by Trypanosoma cruzi and induction of protective mucosal immune responses.

    PubMed Central

    Hoft, D F; Farrar, P L; Kratz-Owens, K; Shaffer, D

    1996-01-01

    Trypanosoma cruzi is an intracellular parasite transmitted from a reduviid insect vector to humans by exposure of mucosal surfaces to infected insect excreta. We have used an oral challenge murine model that mimics vector-borne transmission to study T. cruzi mucosal infection. Although gastric secretions have microbicidal activity against most infectious pathogens, we demonstrate that T. cruzi can invade and replicate in the gastric mucosal epithelium. In addition, gastric mucosal invasion appears to be the unique portal of entry for systemic T. cruzi infection after oral challenge. The mucosal immune responses stimulated by T. cruzi gastric infection are protective against a secondary mucosal parasite challenge. This protective mucosal immunity is associated with increased numbers of lymphocytes that secrete parasite-specific immunoglobulin A. Our results document the first example of systemic microbial invasion through gastric mucosa and suggest the feasibility of a mucosal vaccine designed to prevent infection with this important human pathogen. PMID:8751932

  14. 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-Landín, G; Escobar, K; Montaño, 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 México, Querétaro, México). 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.

  15. Ileal digestibility of nutrients and amino acids in unfermented, fermented soybean meal and canola meal for weaning pigs.

    PubMed

    Upadhaya, Santi D; Kim, In Ho

    2015-04-01

    Apparent ileal digestibility (AID) of energy, dry matter, nitrogen and amino acids and standardized ileal digestibility (SID) of nitrogen and amino acids were evaluated in six weanling pigs ((Landrace × Yorkshire) × Duroc)) fed unfermented soybean meal (SM), yeast fermented soybean meal (SMY), bacillus fermented soybean meal (SMB), yeast and bacillus fermented soybean meal (SMYB), canola meal (CM) and nitrogen-free diet. Pigs having body weights 17.00 ± 0.3 kg were surgically equipped with T-cannulas of approximately 15 cm prior to the ileo-cecal junction and randomly allotted to one of five dietary treatments and a nitrogen-free diet in 6 × 6 Latin squares. AID and SID of nitrogen (N) was greater (P < 0.05) in SMYB and SMB compared with SM and CM. AID and SID of amino acids such as, Lys (lysine) and Phe (phenylalanine) as well as total essential amino acids were greater (P < 0.05) in SMB and tended to be low in CM compared with SM. AID and SID of aspartic acid (Asp) and glycine (Gly) tended to be higher in SMB compared with SM and other diets except CM. In conclusion, fermentation of soybean meal by Bacillus showed better digestibility of amino acid and nutrients.

  16. Adult ileoileal intussusception induced by an ileal lipoma diagnosed preoperatively: report of a case and review of the literature.

    PubMed

    Namikawa, Tsutomu; Hokimoto, Norihiro; Okabayashi, Takehiro; Kumon, Masamitsu; Kobayashi, Michiya; Hanazaki, Kazuhiro

    2012-07-01

    We herein report a case of adult ileoileal intussusception induced by an ileal lipoma. A 68-year-old woman with a history of small intestinal tumors was admitted to our hospital with severe, colicky lower abdominal pain, similar to episodes experienced in the past. A barium meal enema at the initial admission demonstrated a small intestinal tumor in the ileum 30 cm proximal to the ileocecal valve. Abdominal ultrasound sonography and computed tomography showed a sausage-shaped mass presenting as a target sign in the right lower abdomen, suggestive of intussusception. There was also a round mass of fat attenuation representing a lipoma, which was considered the lead point of the intussusception. The patient underwent emergency surgery and partial resection of the ileum, including the ileal tumor, following reduction of the intussusception. The resected specimen contained a round tumor measuring 1.5 × 1.5 × 1.4 cm, which was diagnosed histopathologically as an intestinal lipoma. The patient made a satisfactory recovery and was discharged on postoperative day 10. The clinical characteristics of previously reported lipomas with intussusception are also discussed, including the relationships between the tumor size and symptoms or location.

  17. 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 µm 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 µm and areas more than 20 µm 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 µm 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

  18. 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.

  19. Muscarinic receptor subtypes controlling the cationic current in guinea-pig ileal smooth muscle

    PubMed Central

    Zholos, Alexander V; Bolton, Thomas B

    1997-01-01

    The effects of muscarinic antagonists on cationic current evoked by activating muscarinic receptors with the stable agonist carbachol were studied by use of patch-clamp recording techniques in guinea-pig single ileal smooth muscle cells. Ascending concentrations of carbachol (3–300 μM) activated the cationic conductance in a concentration-dependent manner with conductance at a maximally effective carbachol concentration (Gmax) of 27.4±1.4 nS and a mean −log EC50 of 5.12±0.03 (mean±s.e.mean) (n=114). Muscarinic antagonists with higher affinity for the M2 receptor, methoctramine, himbacine and tripitramine, produced a parallel shift of the carbachol concentration-effect curve to the right in a concentration-dependent manner with pA2 values of 8.1, 8.0 and 9.1, respectively. All M3 selective muscarinic antagonists tested, 4-DAMP, p-F-HHSiD and zamifenacin, reduced the maximal response in a concentration-dependent and non-competitive manner. This effect could be observed even at concentrations which did not produce any increase in the EC50 for carbachol. At higher concentrations M3 antagonists shifted the agonist curve to the right, increasing the EC50, and depressed the maximum conductance response. Atropine, a non-selective antagonist, produced both reduction in Gmax (M3 effect) and significant increase in the EC50 (M2 effect) in the same concentration range. The depression of the conductance by 4-DAMP, zamifenacin and atropine could not be explained by channel block as cationic current evoked by adding GTPγS to the pipette (without application of carbachol) was unaffected. The results support the hypothesis that carbachol activates M2 muscarinic receptors so initiating the opening of cationic channels which cause depolarization; this effect is potentiated by an unknown mechanism when carbachol activates M3 receptors. As an increasing fraction of M3 receptors are blocked by an antagonist, the effects on cationic current of an increasing proportion of

  20. Metformin Improves Ileal Epithelial Barrier Function in Interleukin-10 Deficient Mice

    PubMed Central

    Xue, Yansong; Zhang, Hanying; Sun, Xiaofei; Zhu, Mei-Jun

    2016-01-01

    Background and aims The impairment of intestinal epithelial barrier is the main etiologic factor of inflammatory bowel disease. The proper intestinal epithelial proliferation and differentiation is crucial for maintaining intestinal integrity. Metformin is a common anti-diabetic drug. The objective is to evaluate the protective effects of metformin on ileal epithelial barrier integrity using interleukin-10 deficient (IL10KO) mice. Methods Wild-type and IL10KO mice were fed with/without metformin for 6 weeks and then ileum was collected for analyses. The mediatory role of AMP-activated protein kinase (AMPK) was further examined by gain and loss of function study in vitro. Results Compared to wild-type mice, IL10KO mice had increased proliferation, reduced goblet cell and Paneth cell lineage differentiation in the ileum tissue, which was accompanied with increased crypt expansion. Metformin supplementation mitigated intestinal cell proliferation, restored villus/crypt ratio, increased goblet cell and Paneth cell differentiation and improved barrier function. In addition, metformin supplementation in IL10KO mice suppressed macrophage pro-inflammatory activity as indicated by reduced M1 macrophage abundance and decreased pro-inflammatory cytokine IL-1β, TNF-α and IFN-γ expressions. As a target of metformin, AMPK phosphorylation was enhanced in mice treated with metformin, regardless of mouse genotypes. In correlation, the mRNA level of differentiation regulator including bmp4, bmpr2 and math1 were also increased in IL10KO mice supplemented with metformin, which likely explains the enhanced epithelial differentiation in IL10KO mice with metformin. Consistently, in Caco-2 cells, metformin promoted claudin-3 and E-cadherin assembly and mitigated TNF-α-induced fragmentation of tight junction proteins. Gain and loss of function assay also demonstrated AMPK was correlated with epithelial differentiation and proliferation. Conclusions Metformin supplementation promotes

  1. Standardized Ileal Amino Acid Digestibility of Commonly Used Feed Ingredients in Growing Broilers

    PubMed Central

    Ullah, Zafar; Ahmed, Gulraiz; Nisa, Mehr un; Sarwar, Muhammad

    2016-01-01

    This experiment was conducted to determine standardized ileal amino acid digestibility (SIAAD) of commonly used feed ingredients in poultry diets in Pakistan. These feed ingredients included corn, rice broken (RB), rice polishings (RP), wheat bran (WB), sunflower meal (SFM), cottonseed meal (CSM), guar meal (GM), soybean meal (SBM) from India and Argentine and fish meal (FM). The SIAAD of each ingredient was determined in triplicate using 21-days-old broilers. Day-old male broiler chicks (Hubbard× Hubbard) were reared on corn-SBM based diet from 1 to 13 days and thereafter birds were fed experimental diets from day 14 to 21. Each diet was fed to 36 birds kept in six replicate cages, each cage had six birds. In cereals, the SIAAD of corn’s amino acid (AA) (90.1%) was similar (p>0.05) to RB (89.0%). Isoleucine (97.8%) and lysine (96.9%) were highly digestible AA in corn and RB, respectively. Among cereal-by products, WB’s SIAAD (76.9%) was same (p>0.05) as RP (71.9%). Arginine from WB (82.5%) and RP (83.2%) was highly digestible. However, threonine in WB (72.7%) and leucine in RP (69.6%) were the lowest digestible AAs. In plant protein meals, AAs from Argentine-SBM (85.1%) and Indian-SBM (83.4%) had higher (p<0.5) SIAAD than other protein meals. However, SIAAD of SFM (77.1%) and CSM (71.7%) was intermediate while GM (60.3%) exhibited the lowest (p<0.05) SIAAD among all ingredients. Arginine from GM (76.9%), CSM (85.8%), SBM-India (89.5%) and SBM-Argentine (91.5%) was highly digestible from indispensable AAs. In SFM, methionine (91.4%) SIAAD was the greatest. The average SIAAD of FM was 77.6%. Alanine from FM had the highest (84.0%) but cysteine (62.8%) had the lowest SIAAD. In conclusion, cereals i.e. corn and RB had higher (p<0.05) SIAAD of the cereals by-products. The SIAAD of RP and WB was same (p>0.05). The SBM from plant protein meals had higher (p<0.05) SIAAD than other studied feed ingredients. However, the GM had the lowest (p<0.05) SIAAD among protein

  2. Glutathione peroxidase in early and advanced Parkinson's disease.

    PubMed Central

    Johannsen, P; Velander, G; Mai, J; Thorling, E B; Dupont, E

    1991-01-01

    A defective antioxidant scavenging system plays a major role in one of the theories of the pathogenesis of Parkinson's disease. The aim of this study was to investigate whether there is a general difference in antioxidant activity between early and advanced cases of Parkinson's disease. Twenty five recently diagnosed patients, without any clinical fluctuations (group A), and 25 patients in a late phase of the disease with severe fluctuations in response to levodopa therapy (group B) were included in the study. Erythrocyte glutathione peroxidase was determined as a measure of antioxidant activity and significantly lower values were found in group B than in group A. Regression analyses in groups A and B showed significant correlation between glutathione peroxidase and duration of disease, but not between glutathione peroxidase and age of patients. Images PMID:1940936

  3. Glutathione synthesis is compromised in erythrocytes from individuals with HIV

    PubMed Central

    Morris, Devin; Ly, Judy; Chi, Po-Ting; Daliva, John; Nguyen, Truongson; Soofer, Charleen; Chen, Yung C.; Lagman, Minette; Venketaraman, Vishwanath

    2014-01-01

    We demonstrated that the levels of enzymes responsible for the synthesis of glutathione (GSH) such as glutathione synthase (GSS), glutamate-cysteine ligase-catalytic subunit (GCLC), and glutathione reductase (GSR) were significantly reduced in the red blood cells (RBCs) isolated from individuals with human immunodeficiency virus (HIV) infection and this reduction correlated with decreased levels of intracellular GSH. GSH content in RBCs can be used as a marker for increased overall oxidative stress and immune dysfunctions caused by HIV infection. Our data supports our hypothesis that compromised levels of GSH in HIV infected individuals’ is due to decreased levels of GSH-synthetic enzymes. The role of GSH in combating oxidative stress and improving the functions of immune cells in HIV patients’ indicates the benefit of an antioxidant supplement which can reduce the cellular damage and promote the functions of immune cells. PMID:24782776

  4. Glutathione synthesis is compromised in erythrocytes from individuals with HIV.

    PubMed

    Morris, Devin; Ly, Judy; Chi, Po-Ting; Daliva, John; Nguyen, Truongson; Soofer, Charleen; Chen, Yung C; Lagman, Minette; Venketaraman, Vishwanath

    2014-01-01

    We demonstrated that the levels of enzymes responsible for the synthesis of glutathione (GSH) such as glutathione synthase (GSS), glutamate-cysteine ligase-catalytic subunit (GCLC), and glutathione reductase (GSR) were significantly reduced in the red blood cells (RBCs) isolated from individuals with human immunodeficiency virus (HIV) infection and this reduction correlated with decreased levels of intracellular GSH. GSH content in RBCs can be used as a marker for increased overall oxidative stress and immune dysfunctions caused by HIV infection. Our data supports our hypothesis that compromised levels of GSH in HIV infected individuals' is due to decreased levels of GSH-synthetic enzymes. The role of GSH in combating oxidative stress and improving the functions of immune cells in HIV patients' indicates the benefit of an antioxidant supplement which can reduce the cellular damage and promote the functions of immune cells.

  5. 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

  6. Lipid microparticles for mucosal immunization against hepatitis B.

    PubMed

    Saraf, Surbhi; Mishra, Dinesh; Asthana, Abhay; Jain, Renu; Singh, Surinder; Jain, N K

    2006-01-09

    Parenteral administration of vaccines often does not lead to optimal or long lasting protection against disease causing organisms particularly those that are inhaled, ingested or sexually transmitted. For optimal mucosal protection induction of immune response via mucosal routes is therefore highly desirable. Double emulsion-solvent evaporation (w/o/w) method best suited for water-soluble bioactives was selected for the preparation of hepatitis B surface antigen (HBsAg) loaded lipid microparticles. Intranasal route was considered for mucosal administration and hence to prepare the delivery system biocompatible and least irritable, soyalecithin (phospholipid) was taken instead of polymer because phosphatidylcholine is the major component of endogenous lung surfactant. The studies performed in present work included antigen characterization, development of lipid microparticles, stability studies of the prepared lipid microparticle formulations, percent mucoadhesion, ex vivo cellular uptake studies and in vivo studies. The general order obtained from in vivo studies for mucosal immune response (IgA) followed the sequence: LMST-HBsAg (IN)>LM-HBsAg (IN)>alum-HBsAg (IN)>LMST-HBsAg (IM)>alum-HBsAg (IM)>or=LM-HBsAg (IM)>plain HBsAg (IN)>plain HBsAg (IM).

  7. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey.

    PubMed

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian; Drzewiecki, Krzysztof T; Prause, Jan U; Heegaard, Steffen

    2016-06-01

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma).

  8. 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.

  9. Management and treatment of mucosal melanoma of the genital tract.

    PubMed

    Vaccari, Sabina; Barisani, Alessia; Dika, Emi; Fanti, Pier A; DE Iaco, Pierandrea; Gurioli, Carlotta; Tosti, Giulio

    2017-01-24

    Melanoma of the genital mucosa is a rare melanocytic neoplasm that affects both sexes. The diagnosis is often delayed; a useful diagnostic tool may be represented by videodermatoscopy, The treatment is complex and multidisciplinary. We report the main diagnostic features and therapeutic approaches for mucosal melanoma of the genital tract.

  10. Enhancing the buccal mucosal uptake and retention of triamcinolone acetonide.

    PubMed

    Nicolazzo, Joseph A; Reed, Barry L; Finnin, Barrie C

    2005-07-20

    In this study, the buccal mucosal uptake and retention of triamcinolone acetonide (TAC) were assessed in the presence of the skin penetration enhancer, Azone (AZ). Porcine buccal mucosa was excised, mounted in modified Ussing chambers, and pretreated with ethanolic solutions of AZ. After 2 h, the rate of TAC disappearance from the donor chamber and TAC appearance in the receptor chamber was monitored, and the mucosal retention of TAC was determined at the completion of the experiment. The permeability and mucosal uptake of TAC was also determined using the TAC-containing proprietary product, Kenalog in Orabase (KO), in the presence and absence of AZ. Pretreatment of the buccal mucosa with AZ increased the TAC disappearance permeability coefficient from 4.78+/-0.31x10(-5) cm/s to 7.12+/-0.53x10(-5) cm/s. While the TAC appearance permeability coefficient was also enhanced 3.8-fold, a 4.4-fold increase in the tissue concentration of TAC was observed. Incorporation of AZ into KO did not result in an enhanced tissue concentration of TAC, however, when the tissue was pretreated with AZ, significantly higher amounts of TAC accumulated in the tissue. Pretreatment of the buccal mucosa with AZ results in increased tissue concentrations of TAC, which may be of clinical benefit in the treatment of oral mucosal inflammatory conditions.

  11. The Origin of Mucosal Immunity: Lessons from the Holobiont Hydra

    PubMed Central

    Schröder, Katja

    2016-01-01

    ABSTRACT Historically, mucosal immunity—i.e., the portion of the immune system that protects an organism’s various mucous membranes from invasion by potentially pathogenic microbes—has been studied in single-cell epithelia in the gastrointestinal and upper respiratory tracts of vertebrates. Phylogenetically, mucosal surfaces appeared for the first time about 560 million years ago in members of the phylum Cnidaria. There are remarkable similarities and shared functions of mucosal immunity in vertebrates and innate immunity in cnidarians, such as Hydra species. Here, we propose a common origin for both systems and review observations that indicate that the ultimately simple holobiont Hydra provides both a new perspective on the relationship between bacteria and animal cells and a new prism for viewing the emergence and evolution of epithelial tissue-based innate immunity. In addition, recent breakthroughs in our understanding of immune responses in Hydra polyps reared under defined short-term gnotobiotic conditions open up the potential of Hydra as an animal research model for the study of common mucosal disorders. PMID:27803185

  12. 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.

  13. Mucosal vaccination by adenoviruses displaying reovirus sigma 1

    SciTech Connect

    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.

    2015-08-15

    We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. 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. - Highlights: • Constructed adenoviruses (Ads) displaying different reovirus sigma 1 fusion proteins. • Progressively longer chimeras were more poorly encapsidated onto Ad virions. • Ad5-R3-sigma mediated better systemic and mucosal immune responses than Ad5.

  14. 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 ...

  15. The Mucosal Immune System and Its Regulation by Autophagy

    PubMed Central

    Kabat, Agnieszka M.; Pott, Johanna; Maloy, Kevin J.

    2016-01-01

    The gastrointestinal tract presents a unique challenge to the mucosal immune system, which has to constantly monitor the vast surface for the presence of pathogens, while at the same time maintaining tolerance to beneficial or innocuous antigens. In the intestinal mucosa, specialized innate and adaptive immune components participate in directing appropriate immune responses toward these diverse challenges. Recent studies provide compelling evidence that the process of autophagy influences several aspects of mucosal immune responses. Initially described as a “self-eating” survival pathway that enables nutrient recycling during starvation, autophagy has now been connected to multiple cellular responses, including several aspects of immunity. Initial links between autophagy and host immunity came from the observations that autophagy can target intracellular bacteria for degradation. However, subsequent studies indicated that autophagy plays a much broader role in immune responses, as it can impact antigen processing, thymic selection, lymphocyte homeostasis, and the regulation of immunoglobulin and cytokine secretion. In this review, we provide a comprehensive overview of mucosal immune cells and discuss how autophagy influences many aspects of their physiology and function. We focus on cell type-specific roles of autophagy in the gut, with a particular emphasis on the effects of autophagy on the intestinal T cell compartment. We also provide a perspective on how manipulation of autophagy may potentially be used to treat mucosal inflammatory disorders. PMID:27446072

  16. 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.

  17. The Origin of Mucosal Immunity: Lessons from the Holobiont Hydra.

    PubMed

    Schröder, Katja; Bosch, Thomas C G

    2016-11-01

    Historically, mucosal immunity-i.e., the portion of the immune system that protects an organism's various mucous membranes from invasion by potentially pathogenic microbes-has been studied in single-cell epithelia in the gastrointestinal and upper respiratory tracts of vertebrates. Phylogenetically, mucosal surfaces appeared for the first time about 560 million years ago in members of the phylum Cnidaria. There are remarkable similarities and shared functions of mucosal immunity in vertebrates and innate immunity in cnidarians, such as Hydra species. Here, we propose a common origin for both systems and review observations that indicate that the ultimately simple holobiont Hydra provides both a new perspective on the relationship between bacteria and animal cells and a new prism for viewing the emergence and evolution of epithelial tissue-based innate immunity. In addition, recent breakthroughs in our understanding of immune responses in Hydra polyps reared under defined short-term gnotobiotic conditions open up the potential of Hydra as an animal research model for the study of common mucosal disorders.

  18. Photobiomodulation reduces oral mucositis by modulating NF-kB.

    PubMed

    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

    2015-01-01

    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/cm(2) 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.

  19. Why Chitosan? From properties to perspective of mucosal drug delivery.

    PubMed

    Kumar, Ashwini; Vimal, Archana; Kumar, Awanish

    2016-10-01

    Non-parenteral drug delivery routes primarily remove the local pain at the injection site. The drugs administered through the oral route encounter the process of hepatic first pass metabolism. Among the alternative delivery routes, mucosal route is being investigated as the most preferred route. Different mucosal routes include the gastrointestinal tract (oral), vagina, buccal cavity and nasal cavity. Novel formulations are being developed using natural and synthetic polymers that could increase the residence time of the drug at mucosal surface in order to facilitate permeation and reduce (or bypass) the first pass metabolism. For recombinant drugs, the formulations are accompanied by enzyme inhibitors and penetration enhancers. Buccal cavity (buccal and sublingual mucosa) has smaller surface area than the gastrointestinal tract but the drugs can easily escape the first pass metabolism. Chitosan is the most applied natural polymer while synthetic polymers include Carbopol and Eudragit. Chitosan has inherent properties of mucoadhesion and penetration enhancement apart from biodegradability and efflux pump inhibition. This review hoards the important research purview of chitosan as a compatible drug carrier macromolecule for mucosal delivery on single platform.

  20. Subcellular immunocytochemical analysis detects the highest concentrations of glutathione in mitochondria and not in plastids.

    PubMed

    Zechmann, B; Mauch, F; Sticher, L; Müller, M

    2008-01-01

    The tripeptide glutathione is a major antioxidant and redox buffer with multiple roles in plant metabolism. Glutathione biosynthesis is restricted to the cytosol and the plastids and the product is distributed to the various organelles by unknown mechanisms. In the present study immunogold cytochemistry based on anti-glutathione antisera and transmission electron microscopy was used to determine the relative concentration of glutathione in different organelles of Arabidopsis thaliana leaf and root cells. Glutathione-specific labelling was detected in all cellular compartments except the apoplast and the vacuole. The highest glutathione content was surprisingly not found in plastids, which have been described before as a major site of glutathione accumulation, but in mitochondria which lack the capacity for glutathione biosynthesis. Mitochondria of both leaf and root cells contained 7-fold and 4-fold, respectively, higher glutathione levels than plastids while the density of glutathione labelling in the cytosol, nuclei, and peroxisomes was intermediate. The accuracy of the glutathione labelling is supported by two observations. First, pre-adsorption of the anti-glutathione antisera with glutathione reduced the density of the gold particles in all organelles to background levels. Second, the overall glutathione-labelling density was reduced by about 90% in leaves of the glutathione-deficient Arabidopsis mutant pad2-1 and increased in transgenic plants with enhanced glutathione accumulation. Hence, there was a strong correlation between immunocytochemical and biochemical data of glutathione accumulation. Interestingly, the glutathione labelling of mitochondria in pad2-1 remained very similar to wild-type plants thus suggesting that the high mitochondrial glutathione content is maintained in a situation of permanent glutathione-deficiency at the expense of other glutathione pools. High and constant levels of glutathione in mitochondria appear to be particularly

  1. Subcellular immunocytochemical analysis detects the highest concentrations of glutathione in mitochondria and not in plastids

    PubMed Central

    Zechmann, B.; Mauch, F.; Sticher, L.; Müller, M.

    2008-01-01

    The tripeptide glutathione is a major antioxidant and redox buffer with multiple roles in plant metabolism. Glutathione biosynthesis is restricted to the cytosol and the plastids and the product is distributed to the various organelles by unknown mechanisms. In the present study immunogold cytochemistry based on anti-glutathione antisera and transmission electron microscopy was used to determine the relative concentration of glutathione in different organelles of Arabidopsis thaliana leaf and root cells. Glutathione-specific labelling was detected in all cellular compartments except the apoplast and the vacuole. The highest glutathione content was surprisingly not found in plastids, which have been described before as a major site of glutathione accumulation, but in mitochondria which lack the capacity for glutathione biosynthesis. Mitochondria of both leaf and root cells contained 7-fold and 4-fold, respectively, higher glutathione levels than plastids while the density of glutathione labelling in the cytosol, nuclei, and peroxisomes was intermediate. The accuracy of the glutathione labelling is supported by two observations. First, pre-adsorption of the anti-glutathione antisera with glutathione reduced the density of the gold particles in all organelles to background levels. Second, the overall glutathione-labelling density was reduced by about 90% in leaves of the glutathione-deficient Arabidopsis mutant pad2-1 and increased in transgenic plants with enhanced glutathione accumulation. Hence, there was a strong correlation between immunocytochemical and biochemical data of glutathione accumulation. Interestingly, the glutathione labelling of mitochondria in pad2-1 remained very similar to wild-type plants thus suggesting that the high mitochondrial glutathione content is maintained in a situation of permanent glutathione-deficiency at the expense of other glutathione pools. High and constant levels of glutathione in mitochondria appear to be particularly

  2. Analysis of glutathione, glutathione disulfide, cysteine, homocysteine, and other biological thiols by high-performance liquid chromatography following derivatization by n-(1-pyrenyl)maleimide.

    PubMed

    Winters, R A; Zukowski, J; Ercal, N; Matthews, R H; Spitz, D R

    1995-05-01

    The compound N-(1-pyrenyl)maleimide (NPM) reacts with free sulfhydryl groups to form fluorescent derivatives. A new method for measurement of glutathione and other biological thiols utilizing reverse-phase high-performance liquid chromatography to separate and quantify these derivatives is described. Separation and quantification of glutathione, cysteine, homocysteine, cysteinylglycine, and gamma-glutamylcysteine derivatives are achieved. The method allows for the measurement of glutathione disulfide by masking free glutathione with 2-vinylpyridine, reducing glutathione disulfide with glutathione reductase, and measuring the resulting glutathione. Coefficient of variations for the various thiols measured by the NPM method range from 1.5 to 8.8%. The lower detection limit is around 50 fmol of glutathione. NPM derivatives are shown to be stable for 2 months at 4 degrees C. Between 94.2 and 97.2% of glutathione and/or glutathione disulfide added to a sample is recovered using the NPM method. The NPM method is compared to the monobromobimane high-performance liquid chromatography method and the Tietze assay by measuring glutathione in homogenates from five different cell lines. The newly developed method offers some advantages over the currently accepted techniques, including specificity, speed, sensitivity, and ease of use.

  3. 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

  4. Comparison of amino acid digestibility of feedstuffs determined with the precision-fed cecectomized rooster assay and the standardized ileal amino acid digestibility assay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to evaluate and compare amino acid digestibility of several feedstuffs using 2 commonly accepted methods: the precision-fed cecectomized rooster assay (PFR) and the standardized ileal amino acid assay (SIAAD). Six corn, 6 corn distillers dried grains with or without s...

  5. Salmonella enterica Typhimurium DT104 challenge of pigs using an ileal loop surgical model indicate early host responses involve IL-27 controlled INF pathway

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the early responses of the immune system following infection with Salmonella is necessary in the search for management practices that might improve the health of animals and reduce the economic impact of this pathogen. Using a ligated ileal loop pig model, we challenged with Salmonella...

  6. Interactive effects of age, sex, and strain on apparent ileal amino acid digestibility of soybean meal and an animal by-product blend in broilers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objectives of this study were to determine if age, sex, and strain of broilers affects the apparent ileal amino acid digestibility (AID) of soybean meal (SBM) and an animal by-product blend (ABB). Chicks from two broiler strains, a commercially available and another in the test phase, were obta...

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

    PubMed Central

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

    2016-01-01

    Clostridium perfringens-induced necrotic enteritis is generally controlled by antibiotics. However, because of increasing antibiotic resistance, other antibacterial agents are required, preferably ones that do not affect the beneficial intestinal microbiota of the host. This study evaluated the in vitro selective growth-inhibitory effect of 8-hydroxyquinoline (8HQ) on C. perfringens vs. bifidobacteria in a medium containing chicken ileal digesta. Prior to the experiments, the minimum inhibitory concentrations of 8HQ and penicillin G were determined by broth microdilution assay. The minimum inhibitory concentration values of 8HQ for C. perfringens were 16–32 times lower than the values for bifidobacteria. Treatment of autoclaved and non-autoclaved chicken ileal digesta with 8HQ showed a selective anticlostridial effect. After incubation of C. perfringens with autoclaved ileal digesta for 3 h, all 8HQ concentrations tested (32–2048 μg/mL) significantly reduced C. perfringens bacterial count. In contrast, the same treatment had no or only a slight effect on bifidobacteria counts. Unlike 8HQ, penicillin G did not exhibit any selectivity. Similar results were obtained after incubation for 24 h. In non-autoclaved ileal digesta, all 8HQ concentrations tested significantly reduced C. perfringens bacterial counts after incubation for 30 min and 3 h, while no effect was observed on bifidobacteria. These results suggest that 8HQ may serve as a prospective veterinary compound for use against necrotic enteritis in poultry. PMID:27936245

  8. Changes in α-glucosidase activities along the jejunal-ileal axis of normal rats by the α-glucosidase inhibitor miglitol.

    PubMed

    Mochizuki, Kazuki; Hanai, Emiko; Suruga, Kazuhito; Kuranuki, Sachi; Goda, Toshinao

    2010-10-01

    Miglitol, an α-glucosidase inhibitor that inhibits postprandial hyperglycemia by delaying carbohydrate digestion and absorption along the jejunal-ileal axis, has recently been approved for use in patients with type 2 diabetes mellitus. Miglitol treatment may lead to increased α-glucosidase activities toward the ileum because carbohydrate flow toward the ileum increases. However, it is not yet known if miglitol treatment alters the α-glucosidase activities along the jejunal-ileal axis. In this study, we examined the effects of miglitol supplementation for 3 or 7 days on α-glucosidase activities along the jejunal-ileal axis of Wistar rats. Supplementation with miglitol for 3 or 7 days in rats increased tissue weights of the lower jejunum and ileum, but did not alter tissue weights of the upper jejunum and cecum or the contents of the cecum. Furthermore, supplementation with miglitol for 7 days reduced the activities of isomaltase and maltase in the upper jejunum and increased the activities of sucrase, isomaltase, and maltase in the lower jejunum and ileum. These results suggest that the delay in carbohydrate digestion and absorption along the jejunal-ileal axis by miglitol supplementation in rats is associated with increased α-glucosidase activities toward the ileum.

  9. Fistula formation between the external iliac artery and ileal conduit following a radical cystoprostatectomy: a rare complication with prewarning signs of haemorrhage

    PubMed Central

    Sukha, Anisha; Smyth, Niamh

    2015-01-01

    A 76-year-old man was admitted with bleeding per-urostomy following a collapse at home. Three weeks prior to the admission, he had undergone a radical cystoprostatectomy and formation of ileal-conduit for an extensive bladder carcinoma. A CT angiogram revealed a possible small source of bleeding within the ileal-conduit itself, which settled with conservative management. However, prior to discharge he developed profuse fresh bleeding from the urostomy, which could not be controlled. The patient underwent an emergency endoscopy of the conduit and laparotomy, which revealed a fistula between the right external iliac artery and the proximal end of the ileal-conduit. The right iliac artery was ligated and an emergency left-to-right femoral-femoral crossover bypass was performed. The right ureter was stented and rediverted through the ileal-conduit and the left ureter was stented at a later date. He unfortunately had a stormy postoperative recovery with further episodes of per-urostomy bleeding and no identified source. PMID:25819824

  10. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    2014-01-01

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

  13. Effects of capsicum oleoresin, garlic botanical, and turmeric oleoresin on gene expression profile of ileal mucosa in weaned pigs.

    PubMed

    Liu, Y; Song, M; Che, T M; Bravo, D; Maddox, C W; Pettigrew, J E

    2014-08-01

    This study was conducted to characterize the effects of feeding 3 plant extracts on gene expression in ileal mucosa of weaned pigs. Weaned pigs (n = 32, 6.3 ± 0.2 kg BW, and 21 d old) were housed in individual pens for 9 d and fed 4 different diets: a nursery basal diet as control diet, basal diet supplemented with 10 mg/kg of capsicum oleoresin, garlic botanical, or turmeric oleoresin. Results reported elsewhere showed that the plant extracts reduced diarrhea and increased growth rate of weaning pigs. Total RNA (4 pigs/treatment) was extracted from ileal mucosa of pigs at d 9. Double-stranded cDNA was amplified, labeled, and further hybridized to the microarray. Microarray data were analyzed in R using packages from the Bioconductor project. Differential gene expression was tested by fitting a mixed linear model equivalent to ANOVA using the limma package. Bioinformatics analysis was conducted by DAVID Bioinformatics Resources. Three pairwise comparisons were used to compare each plant extract diet with the control diet. Quantitative real time PCR was applied to verify the mRNA expression detected by microarray. Compared with the control diet, feeding capsicum oleoresin altered (P < 0.05) the expression of 490 genes (280 up, 210 down), and feeding garlic botanical altered (P < 0.05) the expression of 64 genes (33 up, 31 down), while feeding turmeric oleoresin altered (P < 0.05) the expression of 327 genes (232 up, 95 down). Compared with the control diet, feeding capsicum oleoresin and turmeric oleoresin increased [Expression Analysis Systematic Explorer (EASE) < 0.05] the expression of genes related to integrity of membranes and tight junctions, indicating enhanced gut mucosa health, but decreased (EASE < 0.05) the cell cycle pathway. Feeding each of the 3 plant extracts enhanced (EASE < 0.05) the expression of genes associated with immune responses, indicating that feeding these plant extracts may stimulate the immune responses of pigs in the normal conditions

  14. Effects of calcium feeding strategy on true ileal phosphorus digestibility and true phosphorus retention determined with growing broilers.

    PubMed

    Perryman, K R; Masey O'Neill, H V; Bedford, M R; Dozier, W A

    2016-05-01

    An experiment utilizing 960 Ross × Ross 708 male broilers was conducted to determine the effects of Ca feeding strategy on true ileal (prececal) P digestibility (TIPD) and true P retention (TPR) of corn. Experimental diets were formulated with 1 of 3 dietary Ca feeding strategies (0.95%, 0.13%, or variable Ca concentrations to maintain a 2.1:1 Ca:P ratio) and contain 0, 25, 50, or 75% corn. A practical corn-soybean meal diet (1.4:1 Ca:P ratio) was fed as a control. After receiving a common starter diet, experimental diets were fed from 19 to 26 d of age. After a 48-h dietary adaptation period, a 48-h retention assay was conducted. At 25 and 26 d of age, ileal digesta were collected from 8 birds per cage. Broilers consuming the control diet had higher (P<0.001) BW gain, feed intake, digesta P, and excreta P than broilers consuming the corn titration diets. Digesta and excreta P increased (linear, P<0.05) with graded increases of corn. True ileal P digestibility and TPR were highest (P<0.05) for diets with 0.13% Ca (57.3 and 69.5%, respectively) compared with diets formulated with a 2.1:1 Ca:P ratio (41.2 and 37.8%, respectively) or 0.95% Ca (25.4 and 39.0%, respectively). Values for TPR were higher (P<0.05) than those for TIPD except when the dietary Ca:P ratio was fixed. Additionally, negative endogenous P losses were predicted by regression equations when TPR was estimated for birds fed titration diets with the fixed Ca:P ratio. Changing the Ca concentration of the diets to maintain a fixed Ca:P ratio influenced (P<0.001) apparent P retention, which affected the estimate for TPR due to the prediction of negative endogenous P losses. These data demonstrated that regression analysis may have limitations when estimating the TIPD or TPR of corn when formulating diets with different Ca feeding strategies. More research is necessary to elucidate the factors that contributed to regression equations predicting negative endogenous P losses.

  15. Effects of dietary nutrient levels on microbial community composition and diversity in the ileal contents of pregnant Huanjiang mini-pigs

    PubMed Central

    Li, Huawei; Zhu, Qian; Guo, Qiuping; Yin, Yulong

    2017-01-01

    The mammalian gut microbiota influences various metabolic and physiological processes. Substantial metabolic changes occur during a healthy pregnancy that may be related to microbiota composition dynamics. However, the effect of diet on intestinal microbiota composition and diversity during pregnancy remains unclear. We examined the ileal contents of Huanjiang mini-pigs at two pregnancy stages to determine the effects of dietary nutrient levels on such microbial communities. Animals received either a higher-nutrient (HN) diet formulated to meet US National Research Council requirements or a lower-nutrient (LN) diet that met the Chinese National Feeding Standard recommendations. On day 45 or 75 of pregnancy, sows were euthanized and their ileal contents sampled. Experimental diet and pregnancy stage did not affect ileal bacterial richness or diversity, as determined by Chao1 and ACE species richness measures and Shannon and Simpson indices, respectively. The phyla Firmicutes and Proteobacteria, accounting for 69.99–85.44% and 5.82–15.17% of the total reads, respectively, predominated regardless of diet. At the genus level, diet significantly affected the abundance of Lactobacillus species, which was greater in pigs given HN feed (P < 0.05), but had little impact on that of Megasphaera species (P = 0.096). Pregnancy stage had a minimal effect on Proteobacteria numbers (P = 0.053). The number of bacteria of the phylum Firmicutes and genus Lactobacillus decreased, while that of the phylum Proteobacteria, family Enterobacteriaceae, and genus Bacteroides increased between days 45 and 75 of pregnancy. Of the short-chain fatty acids (SCFAs) measured, only propionate levels changed significantly, with higher concentrations observed on day 45 than on day 75. Our findings indicate that Firmicutes and Proteobacteria dominate pregnant sow ileal bacterial profiles. Excepting a tendency for the number of Proteobacteria to increase as pregnancy progressed, pregnancy stage and

  16. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  17. Characterization of glutathione S-transferase of Taenia solium.

    PubMed

    Vibanco-Pérez, N; Jiménez, L; Merchant, M T; Landa, A

    1999-06-01

    A Taenia solium glutathione-S-transferase fraction (SGSTF) was isolated from a metacestode crude extract by affinity chromatography on reduced glutathione (GSH)-sepharose. The purified fraction displayed a specific glutathione S-transferase (GST) activity of 2.8 micromol/min/mg and glutathione peroxidase selenium-independent activity of 0.22 micromol/min/mg. Enzymatic characterization of the fraction suggested that the activity was closer to the mammalian mu-class GSTs. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gel filtration, and enzyme activity analysis showed that the fraction was composed of a major band of Mr = 26 kd and that the active enzyme was dimeric. Immunohistochemical studies using specific antibodies against the major 26-kd band of the SGSTF indicated that GST protein was present in the tegument, parenchyma, protonephridial, and tegumentary cytons of the T. solium metacestode. Antibodies generated against the SGSTF tested in western blot showed cross-reactivity against GSTs purified from Taenia saginata, T. taeniaeformis, and T. crassiceps, but did not react with GSTs from Schistosoma mansoni, or mice, rabbit, and pig liver tissue. Furthermore, immunization of mice with SGSTF reduced the metacestode burden up to 74.2%. Our findings argue in favor of GST having an important role in the survival of T. solium in its hosts.

  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. The effects of exogenous glutathione on reduced glutathione level, glutathione peroxidase and glutathione reductase activities of rats with different ages and gender after whole-body Γ-irradiation.

    PubMed

    Erden Inal, Mine; Akgün, Asiye; Kahraman, Ahmet

    2003-07-01

    Age-and gender-related changes on reduced glutathione (GSH) level, glutathione peroxidase (GPx) and glutathione reductase (GR) activities in the liver of rat exposed to different dose of whole-body g-ray irradiation were determined. In addition, the effect of administration of exogenous GSH on endogenous GSH levels, GPx and GR activities was investigated. For this aim, male and female rats aged 1 and 5 moths were divided into two groups as g-ray and g-ray+GSH. Both groups were again divided into four groups as irradiated with 2, 4, 6 and 8 Gy doses. GSH level and GPx activity did not change with age while GR activity was decreased with age. Gender-dependent changes in GPx and GR activities were observed, but GSH values were not affect by sex. GSH levels, GPx and GR activities were not observed dose-associated changes of g-irradiation. GSH level and GPx activity in the 8Gy group were increased by GSH. GR activities of old male rats were found to be increased by glutathione in the 6 and 8Gy groups. These results indicate that radiation and administration of exogenous GSH affect gender-and age-dependent GSH level, GPx and GR activities in the rats.

  20. 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...

  1. 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...

  2. 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...

  3. Characterization of two Arabidopsis thaliana glutathione S-transferases.

    PubMed

    Nutricati, Eliana; Miceli, Antonio; Blando, Federica; De Bellis, Luigi

    2006-09-01

    Glutathione S-transferases (GST) are multifunctional proteins encoded by a large gene family, divided on the basis of sequence identity into phi, tau, theta, zeta and lambda classes. The phi and tau classes are present only in plants. GSTs appear to be ubiquitous in plants and are involved in herbicide detoxification and stress response, but little is known about the precise role of GSTs in normal plant physiology and during biotic and abiotic stress response. Two cDNAs representing the two plant classes tau and phi, AtGSTF9 and AtGSTU26, were expressed in vitro and the corresponding proteins were analysed. Both GSTs were able to catalyse a glutathione conjugation to 1-chloro-2,4-dinitrobenzene (CDNB), but they were inactive as transferases towards p-nitrobenzylchloride (pNBC). AtGSTF9 showed activity towards benzyl isothiocyanate (BITC) and an activity as glutathione peroxidase with cumene hydroperoxide (CumHPO). AtGSTU26 was not active as glutathione peroxidase and towards BITC. RT-PCR analysis was used to evaluate the expression of the two genes in response to treatment with herbicides and safeners, chemicals, low and high temperature. Our results reveal that AtGSTU26 is induced by the chloroacetanilide herbicides alachlor and metolachlor and the safener benoxacor, and after exposure to low temperatures. In contrast, AtGSTF9 seems not to be influenced by the treatments employed.

  4. 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 ...

  5. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 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 §...

  6. 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 §...

  7. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 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 §...

  8. 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.

  9. 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 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 §...

  10. 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...

  11. 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.

  12. Humoral immune responses among mucosal and cutaneous leishmaniasis patients caused by Leishmania braziliensis.

    PubMed

    Valli, L C; Passos, V M; Dietze, R; Callahan, H L; Berman, J D; Grogl, M

    1999-12-01

    Mucosal leishmaniasis is arguably the most morbid sequelae of cutaneous leishmaniasis. The importance of early diagnosis for effective therapy, coupled with the difficulty of diagnosing the disease parasitologically, prompted this investigation of humoral immune markers of mucosal disease. Promastigote soluble antigens of Leishmania braziliensis, isolated from cutaneous and mucosal lesions, were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis; antigens were identified by immunoblotting with parasite-specific IgG antibody-positive sera of patients with mucosal disease (n = 18) and cutaneous disease (n = 23). For antigens of the cutaneous parasite WR 2095, mucosal sera generally reacted intensely to antigens of 75, 66, and 45 kDa and weakly to 48-50-kDa antigens, whereas cutaneous sera generally detected weakly the first 3 antigens and intensely the latter doublet. The data suggest that the transition from the cutaneous antigenic profile to a mucosal antigenic profile could be used to predict mucosal disease in approximately half of mucosal patients. An additional finding was that antibodies present in the sera of patients with mucosal disease labeled a 66-kDa peptide of normal human lip mucosa more intensely than did cutaneous sera. Autoimmune processes stimulated by the reaction of IgG, originally directed against the 66-kDa of L. braziliensis, to the 66-kDa antigen of mucosal tissue may contribute to the clinical presentation of mucosal leishmaniasis.

  13. 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

  14. 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

  15. Regional gastric mucosal blood flow measurements by hydrogen gas clearance in the anesthetized rat and rabbit.

    PubMed

    Leung, F W; Guth, P H; Scremin, O U; Golanska, E M; Kauffman, G L

    1984-07-01

    Hydrogen gas clearance using 3% hydrogen in air and platinum contact electrodes was employed for measuring antral and corpus mucosal blood flow in anesthetized animals. Significantly greater antral than corpus mucosal blood flow was consistently demonstrated. Corpus but not antral mucosal blood flow showed a significant dose-related increase with intravenous pentagastrin. Vasopressin induced a significant dose-related decrease in both antral and corpus mucosal blood flow. Simultaneous measurement of basal corpus mucosal blood flow by hydrogen gas clearance and of gastric mucosal blood flow by aminopyrine clearance gave similar values, but the changes with intravenous pentagastrin or vasopressin measured by aminopyrine clearance were of a much higher order of magnitude. Hydrogen gas clearance, however, reflected changes in left gastric artery blood flow much more closely than did aminopyrine clearance. Therefore, we conclude that the hydrogen gas clearance technique as described is valid for measuring regional gastric mucosal blood flow. It is safe and has potential application in human studies.

  16. 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.

  17. Dark Agouti rat model of chemotherapy-induced mucositis: Establishment and current state of the art

    PubMed Central

    Vanhoecke, Barbara; Bateman, Emma; Mayo, Bronwen; Vanlancker, Eline; Thorpe, Daniel; Keefe, Dorothy

    2015-01-01

    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

  18. Prolonged fasting increases glutathione biosynthesis in postweaned northern elephant seals.

    PubMed

    Vázquez-Medina, José Pablo; Zenteno-Savín, 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], γ-glutamyl transpeptidase (GGT), glutathione disulphide reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), GST and PrxVI, as well as plasma changes in γ-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 activi