Sample records for ileal mucosal glutathione

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

    Microsoft Academic Search

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

    1987-01-01

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

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

    PubMed

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

    2014-04-28

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

  3. Selenium-dependent glutathione peroxidase-GI is a major glutathione peroxidase activity in the mucosal epithelium of rodent intestine.

    PubMed

    Esworthy, R S; Swiderek, K M; Ho, Y S; Chu, F F

    1998-07-23

    Gpx2 mRNA, encoding a selenium-dependent glutathione peroxidase (GPX-GI), has been found to be highly expressed in the gastrointestinal tract (GI) mucosal epithelium. In this study, we show that GPX-GI is produced in the mucosal epithelium of the adult rat GI tract and that the activity levels are comparable to that from GPX-1. Post-mitochondrial supernatant GPX activity from the mucosal epithelium of the complete length of the small intestine was partially purified. A sample enriched for putative GPX-GI was fractionated by SDS-polyacrylamide gel electrophoresis. Polypeptides of 21 kDa and 22 kDa were digested with trypsin. After resolving the tryptic peptides by high pressure liquid chromatography (HPLC), the major peaks were analyzed for their amino acid sequence by Microflow-HPLC-Tandem Mass Spectrometry and automated Edman degradation sequencing. Both methods revealed that the 21-kDa sample contained rat GPX-GI determined by the sequence homology with the deduced mouse GPX-GI polypeptide sequence. Rat GPX-1 was also detected in the samples. AntiGPX-GI and antiGPX-1 antibodies were used to determine the distribution of the respective isoenzyme activities along the length of the intestine and with respect to the crypt to villus axis in rats. GPX-GI and GPX-1 activities were uniformly distributed in the middle and lower GI tract and with respect to the crypt to villus axis. GPX-GI activity accounted nearly the same percentage of the total GPX activity as GPX-1 in all of the these compartments. Studies on the distal ileum segment of wildtype and Gpx1 gene knockout mice showed that GPX-GI activity was also at parity with GPX-1 in the mucosal epithelium of this segment. PMID:9685647

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

    SciTech Connect

    Aw, Tak Yee [Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932 (United States)]. E-mail: taw@lsuhsc.edu

    2005-05-01

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

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

    Microsoft Academic Search

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

    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

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

    Microsoft Academic Search

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

    1998-01-01

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

  8. [Glutathione and glutathione assays].

    PubMed

    Rousar, Tomás; Cervinková, Zuzana; Muzáková, Vladimíra; Kucera, Otto; Lotková, Halka; Krivákovaá, Pavla

    2005-01-01

    Glutathione, the very important intracellular antioxidant, is present in intracelullar environment in milimolar concentrations. Glutathione is a tripeptide molecule, which plays an essential role in the antioxidant system, as well as in maintenance of the intracellular redox state. This thiol compound exists in two forms, the reduced (GSH) and the oxidized (GSSG), and the ratio of both forms is crucial for the characterization of the oxidative stress in cells. Number of analytical methods have been developed for the measurement of the glutathione. Especially, High Performance Liquid Chromatography methods (HPLC) are mostly used linked to different types of detection, including electrochemical, UV/VIS or fluorimetric detection. Another approach for glutathione assay is using the spectral methods, either fluorimetric or spectrophotometric assays. In enzymatic assay, glutathione reductase reduces GSSG with simultaneous oxidation of specific substrate, which is sequentially photometrically detected. The fluorimetric method is based on the detection of derivatized GSH molecule. PMID:16669486

  9. Oral Mucositis

    Microsoft Academic Search

    Nathaniel Treister

    Mucositis is a common, painful, treatment-disrupting toxicity of both radiotherapy and chemotherapy. Patients with cancers\\u000a of the head and neck receiving radiation therapy with and without induction or concomitant chemotherapy, and individuals being\\u000a treated with high-dose chemotherapy regimens are at particularly high risk. Importantly, even patients receiving conventional\\u000a dosing schemes for other forms of cancer have a meaningful chance of

  10. Mucosal immunology

    PubMed Central

    Bienenstock, J.; Befus, A. D.

    1980-01-01

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

  11. Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat

    PubMed Central

    2012-01-01

    Background Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat. Methods Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression. Results MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels. Conclusions Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat. PMID:22545735

  12. Intestinal Lymphocyte Populations in Children with Regressive Autism: Evidence for Extensive Mucosal Immunopathology

    Microsoft Academic Search

    Paul Ashwood; Andrew Anthony; Alicia A. Pellicer; Franco Torrente; John A. Walker-Smith; Andrew J. Wakefield

    2003-01-01

    Inflammatory intestinal pathology has been reported in children with regressive autism (affected children). Detailed analysis of intestinal biopsies in these children indicates a novel lymphocytic enterocolitis with autoimmune features; however, links with cognitive function remain unclear. To characterize further, the nature and extent of this disease we examined the mucosal infiltrate using flow cytometry. Duodenal, ileal, and colonic biopsies were

  13. Mucosal immunity and vaccines

    Microsoft Academic Search

    Cecil Czerkinsky; Jan Holmgren

    2005-01-01

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

  14. 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

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

    PubMed Central

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

    2012-01-01

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

  16. The S ileal pouch-anal anastomosis

    Microsoft Academic Search

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

    1987-01-01

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

  17. Insect glutathione transferases.

    PubMed

    Ketterman, Albert J; Saisawang, Chonticha; Wongsantichon, Jantana

    2011-05-01

    This article is an overview of the current knowledge of insect glutathione transferases. Three major topics are discussed: the glutathione transferase contributions to insecticide resistance, the polymorphic nature of the insect glutathione transferase superfamily, and a summary of the current structure-function studies on insect glutathione transferases. PMID:21323601

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

    PubMed Central

    2013-01-01

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

  19. Continent ileal bladder: an experimental study in dogs.

    PubMed

    Leisinger, H J; Schauwecker, H; Schmucki, O; Hauri, D; Mayor, G; Säuberli, H

    1975-01-01

    A method for constructing a continent ileal bladder has been tested in dogs. The requirements for a continent ileal bladder: continence, reservoir function, prevention of reflux, could be fulfilled in our experimental study. PMID:1233168

  20. GLUTATHIONE SYNTHESIS

    PubMed Central

    Lu, Shelly C.

    2012-01-01

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

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

    EPA Science Inventory

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

  2. [An ileal neobladder-enteric fistula 10 years after a radical cystectomy with ileal neobladder construction].

    PubMed

    Tohi, Yoichiro; Taketa, Shigeo; Yamamoto, Akihiro; Sakura, Yuma; Sugimoto, Mikio; Kakehi, Yoshiyuki

    2014-12-01

    A 67-year-old male underwent a radical cystectomy and ileal neobladder construction in September 2002. He developed adhesive ileus postoperatively and underwent an intestine-ascending colon bypass operation with a side-to-side anastomosis in December of 2002. Subsequently, the patient developed ileus frequently, which improved with conservative management. In February 2013, he had fecaluria and was diagnosed with an ileal neobladder-enteric fistula based on computed tomography 2 hours after contrast medium injection. He underwent closure of the intestinal anal side of the anastomosis between the intestine and ascending colon. The fecaluria disappeared and he is making steady progress. An ileal neobladderenteric fistula as a long-term postoperative complication of ileal neobladder construction is extremely rare, with no other reports to our knowledge. Here, we discuss its cause, diagnosis and treatment, with reference to previous reports. PMID:25602480

  3. Male issues of the ileal pouch.

    PubMed

    Kani, Haluk T; Shen, Bo

    2015-03-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. 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...

  6. Absorbable staples in continent ileal urinary pouch.

    PubMed

    Bonney, W W; Robinson, R A

    1990-01-01

    Continent ileal urinary reservoirs were created in dogs to study absorbable surgical staples. Within each pouch, certain controlled observations were possible. The staples and chemically similar polyglactin absorbable sutures caused almost identical tissue reactions. The staples outlasted the sutures, probably because of greater size. Inverted and everted staple closures worked equally well. It appears feasible to consider clinical urinary diversion with absorbable staples, a time-saving method. PMID:2404367

  7. Gasoline-induced mucositis

    SciTech Connect

    Hoffman, D.L.; Swanson, B.Z. Jr.; Lutins, N.D.

    1980-02-01

    Gasoline-induced mucositis may become more common because of fuel shortages or increased fuel cost. Dentists should, therefore, consider this oral irritant in the differential diagnosis of oral lesions.

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

    Microsoft Academic Search

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

    1984-01-01

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

  9. New frontiers in mucositis.

    PubMed

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

    2012-01-01

    Mucositis is among the most debilitating side effects of radiotherapy, chemotherapy, and targeted anticancer therapy. Research continues to escalate regarding key issues such as etiopathology, incidence and severity across different mucosae, relationships between mucosal and nonmucosal toxicities, and risk factors. This approach is being translated into enhanced management strategies. Recent technology advances provide an important foundation for this continuum. For example, evolution of applied genomics is fostering development of new algorithms to rapidly screen genomewide single-nucleotide polymorphisms (SNPs) for patient-associated risk prediction. This modeling will permit individual tailoring of the most effective, least toxic treatment in the future. The evolution of novel cancer therapeutics is changing the mucositis toxicity profile. These agents can be associated with unique mechanisms of mucosal damage. Additional research is needed to optimally manage toxicity caused by agents such as mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors, without reducing antitumor effect. There has similarly been heightened attention across the health professions regarding clinical practice guidelines for mucositis management in the years following the first published guidelines in 2004. New opportunities exist to more effectively interface this collective guideline portfolio by capitalizing upon novel technologies such as an Internet-based Wiki platform. Substantive progress thus continues across many domains associated with mucosal injury in oncology patients. In addition to enhancing oncology patient care, these advances are being integrated into high-impact educational and scientific venues including the National Cancer Institute Physician Data Query (PDQ) portfolio as well as a new Gordon Research Conference on mucosal health and disease scheduled for June 2013. PMID:24451793

  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

    2014-06-01

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

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

    PubMed Central

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

    2014-01-01

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

  12. Bacterial overgrowth in jejunal and ileal disease.

    PubMed

    Bjørneklett, A; Fausa, O; Midtvedt, T

    1983-03-01

    The number of bacteria recovered in anaerobic cultures of jejunal secretions was significantly higher in a group of 10 patients with jejunal disease and stagnation of gut content in the proximal small bowel than in a group of 10 patients with similar conditions in the distal ileum. Some overlap in bacterial numbers occurred between patients with jejunal disease, ileal disease, and healthy controls, whereas production of fermentation gas in anaerobic media supplemented with glucose occurred only in cultures from the patients with jejunal disease. The 14C-glycocholic acid test showed increased output of breath 14CO2 in both patient groups, whereas faecal 14C was significantly increased only in patients with ileal disease. Increased breath hydrogen excretion after glucose ingestion was recorded in 8 of 10 patients with jejunal disease only. Breath methane excretion, previously found in 44% of healthy subjects, was absent in all of 28 patients with Crohn's disease of the small, indicating that these patients have a gut flora that is different from that of the healthy population. PMID:6369510

  13. Delayed complication of pelvic lymphocele: Ileal conduit obstruction

    PubMed Central

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

    2015-01-01

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

  14. 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 ? (IFN?) 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 IFN?, 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 IFN?-producing CD3+ cells was observed (p=0.02) in patients with SpA. In the CD3+CD8? subset, the proportion of cells producing IFN? 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

  15. Scoring oral mucositis

    Microsoft Academic Search

    W Parulekar; R Mackenzie; G Bjarnason; R. C. K Jordan

    1998-01-01

    Oral mucositis is a common, dose limiting and potentially serious complication of both radiation and chemotherapy. Both these therapies are non-specific, interfering with the cellular homeostasis of both malignant and normal host cells. An important effect is the loss of the rapidly proliferating epithelial cells in the oral cavity, gut and in the bone marrow. Within the mouth, the loss

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

    EPA Science Inventory

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

  17. Endotoxin-induced ileal Vo 2Do 2 alterations do not correlate with the severity of ileal injury

    Microsoft Academic Search

    Elliott D. Crouser; Mark W. Julian; Steven E. Weisbrode; Paul M. Dorinsky

    1997-01-01

    Purpose: Altered Vo2-Do2 relationships are most often noted to occur in the setting of sepsis or endotoxin (LPS)-induced systemic organ microvascular injury and are generally thought to be causally linked to that injury. However, we have recently shown that ileal microvascular injury is not associated with altered ileal Vo2-Do2 relationships. Thus, we hypothesized that the severity of LPS-induced systemic organ

  18. Local regulation of postprandial motor responses in ileal pouches

    PubMed Central

    Mularczyk, A; Contessini-Avesan..., E; Cesana, B; Bianchi, P; Basilisco, G

    1999-01-01

    BACKGROUND—Local mechanisms are involved in the postprandial regulation of ileal tone in healthy subjects, but whether these mechanisms affect the postprandial tonic response of ileal pouches has not yet been investigated.?AIMS—To study the effect of a meal on pouch tone and phasic motor activity in patients with gut continuity or ileostomy and, in the latter group, the effect of a pouch perfusion with chyme or saline.?PATIENTS—Twenty patients with ileal pouches: 10 with gut continuity and 10 with ileostomy.?METHODS—Pouch tone and the frequency of phasic volume events were recorded with a barostat under fasting and postprandial conditions and after perfusion of the isolated pouch with chyme or saline.?RESULTS—The meal increased pouch tone and the frequency of phasic volume events in the patients with gut continuity, but not in those with ileostomy. Pouch perfusion with chyme induced a greater increase in pouch tone than saline.?CONCLUSIONS—The meal stimulated pouch tone and phasic motor activity. These effects were at least partially related to local pouch stimulation by intraluminal contents.???Keywords: ileal pouches; postprandial motor responses; ileal tone; ileostomy; motor activity; barostat PMID:10486368

  19. Dehydroalanine analog of glutathione

    PubMed Central

    Younis, Islam R.; Elliott, Meenal; Peer, Cody J.; Cooper, Arthur J.L.; Pinto, John T.; Konat, Gregory W.; Kraszpulski, Michal; Petros, William P.; Callery, Patrick S.

    2008-01-01

    Elimination of hydrogen sulfide from glutathione (GSH) converts a well-known cellular nucleophile to an electrophilic species, ?-glutamyldehydroalanylglycine (EdAG). We have found that a sulfonium metabolite formed from GSH and busulfan undergoes a facile ?-elimination reaction to give EdAG, which is an ??-unsaturated dehydroalanyl analog of GSH. EdAG was identified as a metabolite of busulfan in a human liver cytosol fraction. EdAG condenses with GSH in a Michael addition reaction to produce a lanthionine thioether (GSG), which is a non-reducible analog of glutathione disulfide (GSSG). EdAG was less cytotoxic than busulfan to C6 rat glioma cells. GSH and EdAG were equally effective in displacing a glutathione S-transferase isozyme (human GSTA1-1) from a GSH-Agarose column. The finding of an electrophilic metabolite of GSH suggests that alteration of cellular GSH concentrations, irreversible non-reducible glutathionylation of proteins, and interference with GST function may contribute to the toxicity of busulfan. PMID:18791061

  20. 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. PMID:24998385

  1. Head and Neck Mucosal Melanoma

    Microsoft Academic Search

    William M. Mendenhall; Robert J. Amdur; Russell W. Hinerman; John W. Werning; Douglas B. Villaret; Nancy Price Mendenhall

    2005-01-01

    Purpose: The purpose of this article is to discuss the optimal treatment and outcomes for head and neck mucosal melanoma. Methods: Review the pertinent literature. Results: Head and neck mucosal melanoma is a rare entity com- prising less than 1% for all Western melanomas. It usually arises in the nasal cavity, paranasal sinuses, and oral cavity. The optimal treatment is

  2. NKT cells in mucosal immunity

    Microsoft Academic Search

    S Middendorp; E E S Nieuwenhuis; EES Nieuwenhuis

    2009-01-01

    The gastrointestinal tract allows the residence of an almost enumerable number of bacteria. To maintain homeostasis, the mucosal immune system must remain tolerant to the commensal microbiota and eradicate pathogenic bacteria. Aberrant interactions between the mucosal immune cells and the microbiota have been implicated in the pathogenesis of inflammatory disorders, such as inflammatory bowel disease (IBD). In this review, we

  3. An investigation of human jejunal and ileal arteries.

    PubMed

    Conley, Dylan; Hurst, Peter R; Stringer, Mark D

    2010-03-01

    The arrangement of jejunal and ileal arteries varies along the length of the small bowel, but the reasons for this and the functional implications are uncertain. The aims of this anatomical and histological study were to investigate quantitative differences between jejunal and ileal arteries and to investigate their relative muscularity. Ten cadaver small bowels (five males, mean age 78 years) were analysed. In each specimen, the mesentery of two standardised 40-cm lengths of jejunum and ileum were dissected and measured. Representative arterial samples from a jejunal and ileal parent artery, first arcade artery and arteriae recta were examined histologically and their relative muscularity (proportion of arterial cross sectional area occupied by tunica media) compared. No consistent differences were found between jejunal and ileal parent artery lengths, but jejunal arteries tended to be larger (mean diameter 2.2 +/- 0.2 mm vs. 2.0 +/- 0.4 mm, p = 0.08). Compared to the jejunum, the number of arterial arcades was significantly greater in the ileum (p < 0.0001), and the arteriae recta were more numerous (p = 0.02), shorter (p = 0.007) and narrower (p = 0.004). There was no statistically significant difference between the muscularity of proximal jejunal versus distal ileal arteries or between parent, first arcade and arteriae recta within the proximal jejunum and distal ileum. These quantitative data clarify conflicting statements about jejunal and ileal arterial anatomy. However, the different arterial pattern in the jejunum and ileum does not appear to be associated with differences in the muscularity of these arteries. PMID:19488686

  4. Histopathological study of colo-ileal carcinoma

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    Microsoft Academic Search

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

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

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

    PubMed

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

    2013-11-01

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

  9. Glutathione transferases and neurodegenerative diseases.

    PubMed

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

    2015-03-01

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

  10. Alteration of the redox state with reactive oxygen species for 5-fluorouracil-induced oral mucositis in hamsters.

    PubMed

    Yoshino, Fumihiko; Yoshida, Ayaka; Nakajima, Atsushi; 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

  11. 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

  12. Mucosal Vaccination Against HIV1

    Microsoft Academic Search

    Tom Evans

    Sexual mucosal transmission of HIV-1 is the most common means of spread of HIV\\/AIDS throughout the world. Although it may\\u000a be reasonable to assume that a vaccine that works to eliminate viral replication in the systemic lymphoid tissue may be partially\\u000a protective, there is still a reasonable belief that a vaccine that engenders high level of immune defenses at mucosal

  13. Role of glutathione modulation in acrylonitrile-induced gastric DNA damage in rats

    Microsoft Academic Search

    Ahmed E. Ahmed; Amr M. Nouraldeen; Sherif Z. Abdel-Rahman; Srinivasan Rajaraman

    1996-01-01

    Acrylonitrile (VCN) or its reactive metabolites irreversibly interact with gastric DNA in vivo and cause DNA damage. The\\u000a effect of glutathione (GSH) modulation on VCN-induced genotoxicity and unscheduled DNA repair synthesis (UDRS) in DNA of gastric\\u000a mucosal tissues was investigated. VCN-induced UDRS was determined: in control rats, rats with depleted gastric GSH contents,\\u000a and rats treated with sulfhydryl compounds. A

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

    PubMed Central

    2014-01-01

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

  15. Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins

    PubMed Central

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

    1971-01-01

    The effects of several prostaglandins (PG) and a highly purified preparation of cholera enterotoxin (CT) on intestinal mucosal adenyl cyclase activity and the effect of CT on intestinal mucosal cyclic 3?,5?-adenosine monophosphate concentration were determined in guinea pig and rabbit small intestine and were correlated with the effects of the same agents on ion transport. Adenyl cyclase activity, measured in a crude membrane fraction of the mucosa, was found at all levels of the small intestine with the highest activity per milligram protein in the duodenum. The prostaglandins, when added directly to the assay, increased adenyl cyclase activity; the greatest effect (2-fold increase) was obtained with PGE1 (maximal effect at 0.03 mM) and PGE2. The prostaglandins also increased short-circuit current (SCC) in isolated guinea pig ileal mucosa, with PGE1 and PGE2 again giving the greatest effects. The prior addition of theophylline (10 mM) reduced the subsequent SCC response to PGE1 and vice versa. It was concluded, therefore, that the SCC response to PGE1, like the response to theophylline, represented active Cl secretion. CT increased adenyl cyclase activity in guinea pig and rabbit ileal mucosa when preincubated with the mucosa from 1 to 2.5 hr in vitro or for 2.5 hr in vivo but not when added directly to the assay. The increments in activity caused by PGE1 and NaF were the same in CT-treated and control mucosa. Cyclic 3?,5?-AMP concentration in rabbit ileal mucosa was increased 3.5-fold after a 2 hr preincubation with CT in vitro. Phosphodiesterase activity in the crude membrane fraction of the mucosa was unaffected by either CT or PGE1. A variety of other agents including insulin, glucagon, parathormone, thyroid-stimulating hormone, L-thyroxine, thyrocalcitonin, vasopressin, and epinephrine all failed to change adenyl cyclase activity. It is concluded that CT and certain prostaglandins produce small intestinal fluid secretion by increasing mucosal adenyl cyclase activity, thereby stimulating an active secretory process. PMID:4325309

  16. Evaluating standardized ileal digestibility of amino acids in growing pigs

    Microsoft Academic Search

    Y.-L. Yin; T.-J. Li; R.-L. Huang; Z.-Q. Liu; X. F. Kong; W.-Y. Chu; B.-E. Tan; D.-Deng; P. Kang; F.-G. Yin

    2008-01-01

    The ileal digestibility coefficient (CSID) of amino acids (AA) and crude protein (CP) in 40 feedstuffs for growing pigs were determined with the protein-free (PF) and enzyme-hydrolyzed casein (EHC) methods. The 40 feedstuffs that were used earlier were 10 samples of cereals and cereal by-products, 12 samples of legumes, 6 samples of animal protein feedstuff and 12 samples of oil

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

    E-print Network

    Chapman, Michael S.

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

  18. Glutathione Synthesis in Human Erythrocytes

    PubMed Central

    Majerus, Philip W.; Brauner, M. J.; Smith, M. B.; Minnich, Virginia

    1971-01-01

    The two enzymes required to synthesize glutathione de novo have been purified from human erythrocytes. Glutamylcysteine synthetase was purified 4300-fold and was approximately 80% pure based on polyacrylamide gel electrophoresis. The purified enzyme catalyzes the formation of 30.5 ?moles of ?-glutamyl-cysteine per mg of protein per hr and is inhibited by sulfhydryl inhibitors. Glutathione synthetase was purified 6000-fold from erythrocytes to homogeneity as determined by polyacrylamide gel electrophoresis. The erythrocyte enzyme has a molecular weight of 150,000 and catalyzes the formation of 35.9 ?moles of glutathione per mg of protein per hr. Comparison of the amino acid composition and some kinetic parameters of yeast glutathione synthetase and the erythrocyte enzyme demonstrate similarities between these enzymes. Images PMID:5097571

  19. Glutathione and mitochondria

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. Mucosal immunity and the microbiome.

    PubMed

    Neish, Andrew S

    2014-01-01

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

  2. PRION INFECTION OF MUCOSAL TISSUE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To investigate the site(s) of prion agent shedding in chronic wasting disease (CWD), we examined the distribution of the prion agent in mucosal tissue from ruminants and rodents with experimental prion disease. We chose the tongue as a peripheral target of prion infection since is a densely innervat...

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

    PubMed

    Davis, Heather A; Munsterman, Amelia

    2012-01-01

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

  4. Digestion of milk proteins and lysosomal proteinases of the ileal mucosa of young rats

    Microsoft Academic Search

    V. R. Nikolaevskaya; M. P. Chernikov

    1979-01-01

    To study whether lysosomal proteinases of the ileal mucosa can participate in intraluminal digestion, the proteolytic activity of lysosomal and pancreatic proteinases was determined both in the chyme and in a homogenate of ileal and jejunal tissues from rats aged 12 and 30 days. In the period of milk feeding the proteolytic activity of acid (lysosomal) proteinases was shown to

  5. Primary mucosal melanomas: a comprehensive review.

    PubMed

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

    2012-01-01

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

  6. 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

  7. Glutathione transferases: a structural perspective.

    PubMed

    Oakley, Aaron

    2011-05-01

    The glutathione transferases (GSTs) are one of the most important families of detoxifying enzymes in nature. The classic activity of the GSTs is conjugation of compounds with electrophilic centers to the tripeptide glutathione (GSH), but many other activities are now associated with GSTs, including steroid and leukotriene biosynthesis, peroxide degradation, double-bond cis-trans isomerization, dehydroascorbate reduction, Michael addition, and noncatalytic "ligandin" activity (ligand binding and transport). Since the first GST structure was determined in 1991, there has been an explosion in structural data across GSTs of all three families: the cytosolic GSTs, the mitochondrial GSTs, and the membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG family). In this review, the major insights into GST structure and function will be discussed. PMID:21428697

  8. Influence of heated and nonheated partially hydrogenated dietary fats on ileal chyme fat and fatty acid composition of ileal mucosa in pigs

    Microsoft Academic Search

    SABINE BIJHNER; Eckhard Nagel; Hermann Stockhorst; Jürgen Körber; Angelos N. Sagredos; Rudolf Pichlmayr

    1995-01-01

    In this study the effects of partially hydrogenated chemically processed fats (CPF) and non-CPF on the ileal chyme fat and the fatty acid (FA) profile of the ileal mucosa and the subcutaneous tissue were analyzed. Samples were collected via an ileocutaneous fistula. For three months pigs were fed a control meal or diets containing either non-CPF high on 16:0, non-CPF

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

    PubMed

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

    2015-04-01

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

  10. Correlations between antibody immune responses at different mucosal effector sites are controlled by antigen type and dosage.

    PubMed

    Externest, D; Meckelein, B; Schmidt, M A; Frey, A

    2000-07-01

    Monitoring specific secretory immunoglobulin A (IgA) responses in the intestines after mucosal immunization or infection is impeded by the fact that sampling of small intestinal secretions requires invasive methods not feasible for routine diagnostics. Since IgA plasma cells generated after intragastric immunization are known to populate remote mucosal sites as well, secretory IgA responses at other mucosal surfaces may correlate to those in the intestines and could serve as proxy measures for IgA secretion in the gut. To evaluate the practicability of this approach, mice were immunized intragastrically with 0.2, 2, and 20 mg of ovalbumin plus 10 microg of cholera toxin, and the antigen-specific local secretory IgA responses in duodenal, ileal, jejunal, rectal, and vaginal secretions, saliva, urine, and feces, as well as serum IgG and IgA responses were analyzed by enzyme-linked immunosorbent assay. Correlation analysis revealed significant relationships between serum IgG and IgA, urinary IgA, salivary IgA, and secretory IgA in duodenal, jejunal, ileal, and rectal secretions for the 0.2-mg but not for the 20-mg ovalbumin dose. Fecal samples were poor predictors for intestinal antiovalbumin IgA responses, and no correlations could be established for cholera toxin, neither between local anti-cholera toxin levels nor to the antiovalbumin responses. Thus, specific IgA in serum, saliva, or urine can serve as a predictor of the release of specific IgA at intestinal surfaces after intragastric immunization, but the lack of correlations for high ovalbumin doses and for cholera toxin indicates a strong dependency on antigen type and dosage for these relationships. PMID:10858191

  11. Hepatic portal venous gas and portal venous thrombosis following colonoscopy in a patient with terminal ileal Crohn's disease.

    PubMed

    Ma, Adler Shing Chak; Ewing, Iain; Murray, Charles Daniel; Hamilton, Mark Ian

    2015-01-01

    A 27-year-old man developed extensive hepatic portal venous gas (HPVG) shortly after staging colonoscopy for active, ulcerating, terminal ileal Crohn's disease. Non-operative management was instigated with broad-spectrum antibiotics and thromboprophylaxis. Radiology at 72?h demonstrated resolution of HPVG but revealed fresh non-occlusive left portal vein thrombus. Anticoagulation with warfarin was continued for 1?year, during which the thrombus initially progressed and then organised with recanalisation of the portal vein. There were no long-term clinical consequences. HPVG has previously been documented as a rare complication of inflammatory bowel disease and endoscopic intervention. We hypothesise that the barotrauma sustained during endoscopy, in association with active ulceration and mucosal friability, predisposes to the influx of gas and bacteria into the portal system. We describe successful non-operative management of HPVG in this setting and draw attention to an additional complication of portal venous thrombosis, highlighting the importance of thromboprophylaxis and serial radiological examination. PMID:25939971

  12. Ontogeny of glutathione and glutathione-related antioxidant enzymes in rat liver

    Microsoft Academic Search

    Fawzy Elbarbry; Jane Alcorn

    2009-01-01

    We conducted a comprehensive characterization of the ontogeny of glutathione (GSH) and its related enzymes in rat liver. GSH content and activities of glutathione reductase (GR), cytosolic glutathione-S-transferases (GST), and glutathione peroxidase (GPx) were determined in male rat livers (n=4) at different developmental stages. Our results indicate total hepatic GSH content and GR, GST, and GPx activity were low in

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    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. PMID:23180972

  15. Enzymatic treatment of ileal segments used for urinary tract reconstruction.

    PubMed

    Türkeri, L N; Sim?ek, F; Sav, A; Ilker, Y N; Akda?, A

    1996-01-01

    Urinary tract reconstruction by using various gastrointestinal segments is not devoid of complications which may hamper to a great extent the beneficial effects of the procedure. Intestinal mucosa is the primary site responsible for these complications and any procedure aiming at the prevention of untoward effects of intestinal interposition should abolish the absorptive and secretory functions of the mucosa. Augmentation cystoplasties by ileal segments were performed on 24 male albino Wistar rats. In 12 animals de-epithelialization of the mucosa with an enzymatic cock-tail, consisting of type I and type V collagenases and trypsin, preceded the cystoplasty. The functional capacity of the epithelium was determined by a simplified glucose absorption test in the third postoperative week. Morphological examination before the absorption test did not reveal any fibrosis or shrinkage of the ileal segments. Complete elimination of the absorptive capability in enzyme treated mucosa was found during the glucose absorption test, while a rapid and highly effective absorption was observed in the control group (p < 0.05). As a result, it seems possible to obtain intestinal segments covered with a mucosa which acquired similar characteristics to uro-epithelium, therefore closely resembling the original urinary tissues. PMID:9061425

  16. Jejuno–ileal diverticulitis: Etiopathogenicity, diagnosis and management

    PubMed Central

    Kassir, Radwan; Boueil-Bourlier, Alexia; Baccot, Sylviane; Abboud, Karine; Dubois, Joelle; Petcu, Carmen Adina; Boutet, Claire; Chevalier, Ugo; Montveneur, Mathias; Cano, Marie-Isabelle; Ferreira, Romain; Debs, Tarek; Tiffet, Olivier

    2015-01-01

    Introduction Although diverticular disease of the duodenum and colon is frequent, the jejuno–ileal diverticulosis (JOD) is an uncommon entity. The perforation of the small bowel diverticula can be fatal due to the delay in diagnosis. Presentation of case We report the case of a 79-year-old man presenting with generalized abdominal pain and altered bowel habits. Physical examination revealed a severe diffuse abdominal pain. A CT scan of the abdomen and pelvis with oral contrast showed thickening of the distal jejunal loop and thickening and infiltration of the mesenteric fat and the presence of free air in the mesentery suggesting a possible perforation adjacent to the diverticula. A midline laparotomy was performed. The jejunal diverticula were found along the mesenteric border. Forty centimeters of the jejunum were resected. Histopathology report confirmed the presence of multiple jejunual diverticula, and one of them was perforated. The patient tolerated the procedure and the postoperative period was uncomplicated. Discussion The prevalence of small intestinal diverticula ranges from 0.06% to 1.3%. The etiopathogenesis of JOD is unclear, although the current hypothesis focuses on abnormalities in the smooth muscle or myenteric plexus, on intestinal dyskinesis and on high intraluminal pressures. Diagnosis is often difficult and delayed because clinical symptoms are not specific and mainly imaging studies performs the diagnosis. Conclusion Because of the relative rarity of acquired jejuno–ileal diverticulosis, the perforation of small bowel diverticulitis poses technical dilemmas. PMID:25841158

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

    Microsoft Academic Search

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

    2005-01-01

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

  18. Sensory peptide neurotransmitters mediating mucosal and distension evoked neural vasodilator reflexes in guinea pig ileum.

    PubMed

    Patton, D; O'Reilly, M; Vanner, S

    2005-11-01

    The aim was to determine the role CGRP and/or tachykinins released from sensory neural mechanisms in enteric neural vasodilator pathways. These pathways project through the myenteric plexus to submucosal vasodilator neurons. Submucosal arterioles were exposed in the distal portion of an in vitro combined submucosal-myenteric guinea pig ileal preparation, and dilation was monitored with videomicroscopy. Vasodilator neural reflexes were activated by gently stroking the mucosa with a fine brush or by distending a balloon placed beneath the flat-sheet preparation in the proximal portion. Dilations evoked by mucosal stroking were inhibited 64% by the CGRP 8-37 and 37% by NK3 (SR 142801) antagonists. When the two antagonists were combined with hexamethonium, only a small vasodilation persisted. Balloon distension-evoked vasodilations were inhibited by NK3 antagonists (66%) but were not altered by CGRP 8-37. In preparations in which myenteric descending interneurons were directly activated by electrical stimulation, combined application of CGRP 8-37 and the NK antagonists had no effect. Stimulation of capsaicin sensitive nerves in the myenteric plexus did not activate these vasodilator reflexes. These findings suggest that mucosal-activated reflexes result from the release of CGRP and tachykinins from enteric sensory neurons. Distension-evoked responses were significantly blocked by NK3 antagonists, suggesting that stretch activation of myenteric sensory neurons release tachykinins that activate NK3 receptors on myenteric vasodilator pathways. PMID:15976390

  19. Binding and glutathione conjugation of porphyrinogens by plant glutathione transferases.

    PubMed

    Dixon, David P; Lapthorn, Adrian; Madesis, Panagiotis; Mudd, Elisabeth A; Day, Anil; Edwards, Robert

    2008-07-18

    Overexpression in Escherichia coli of a tau (U) class glutathione transferase (GST) from maize (Zea mays L.), termed ZmGSTU1, caused a reduction in heme levels and an accumulation of porphyrin precursors. This disruption was highly specific, with the expression of the closely related ZmGSTU2 or other maize GSTs having little effect. Expression in E. coli of a series of chimeric ZmGSTU1/ZmGSTU2 proteins identified domains responsible for disrupting porphyrin metabolism. In addition to known heme precursors, expression of ZmGSTU1 led to the accumulation of a novel glutathione conjugate of harderoporphyrin(ogen) (2,7,12,18-tetramethyl-3-vinylporphyrin-8,13,17-tripropionic acid). Using the related protoporphyrinogen as a substrate, conjugation could be shown to occur on one vinyl group and was actively catalyzed by the ZmGSTU. In plant transgenesis studies, the ZmGSTUs did not perturb porphyrin metabolism when expressed in the cytosol of Arabidopsis or tobacco. However, expression of a ZmGSTU1-ZmGSTU2 chimera in the chloroplasts of tobacco resulted in the accumulation of the harderoporphyrin(ogen)-glutathione conjugate observed in the expression studies in bacteria. Our results show that the well known ability of GSTs to act as ligand binding (ligandin) proteins of porphyrins in vitro results in highly specific interactions with porphyrinogen intermediates, which can be demonstrated in both plants and bacteria in vivo. PMID:18492666

  20. 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 ?mol/g tissue, P < 0.05) in the jejunum, whereas in the liver glutathione remained low. Glutamine markedly increased jejunal ?1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model. PMID:17569119

  1. Voice Disorders in Mucosal Leishmaniasis

    PubMed Central

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

    2014-01-01

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

  2. Endrin-induced depletion of glutathione and inhibition of glutathione peroxidase activity in rats.

    PubMed

    Numan, I T; Hassan, M Q; Stohs, S J

    1990-01-01

    1. Recent studies have shown that endrin induces lipid peroxidation and may produce toxicity through an oxidative stress. We have therefore examined the effect of endrin administration to rats on glutathione content and the activities of glutathione metabolizing enzymes. 2. The oral administration of endrin resulted in dose- and time-dependent decreases in hepatic and renal glutathione content with maximum depletion (90%) occurring in liver at approximately 24 hr post-treatment. 3. Decreases in glutathione content were also observed in lung, brain, spleen and heart. 4. Endrin (4 mg/kg) decreased selenium dependent glutathione peroxidase activity in liver and kidney by 64 and 50%, respectively, while small increases were observed in the activities of glutathione reductase and glutathione S-transferase. 5. The toxicity of endrin may be at least in part related to oxidative tissue damage associated with depletion of glutathione and inhibition of glutathione peroxidase activity. PMID:2276583

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2013-07-01

    Amino acid compositions of ovine muscle, ovine myofibrillar protein, ovine spleen, ovine liver, bovine blood plasma, bovine blood globulins and bovine serum albumin and the amino acid compositions and in vivo (laboratory rat) true ileal amino acid digestibilities of hydrolysates (sequential hydrolysis with Neutrase, Alcalase and Flavourzyme) of these protein sources were determined. True ileal amino acid digestibility differed (P<0.05) among the seven protein hydrolysates. The ovine myofibrillar protein and liver hydrolysates were the most digestible, with a mean true ileal digestibility across all amino acids of 99%. The least digestible protein hydrolysate was bovine serum albumin with a comparable mean true ileal digestibility of 93%. When the digestible amino acid contents were expressed as proportions relative to lysine, considerable differences, across the diverse protein sources, were found in the pattern of predicted absorbed amino acids. PMID:23567135

  6. Ileal atresia secondary to antenatal strangulation of Littre's hernia in an exomphalos minor

    PubMed Central

    Patel, Ramnik V; Khoo, A Kate; De Coppi, Paolo; Pierro, Agostino

    2013-01-01

    We describe an unusual case of ileal atresia, resulting from antenatal strangulation of a Meckel’s diverticulum in an exomphalos minor. This is a rare antenatal complication of Littre’s hernia, which has not been previously described. A small exomphalos minor at the base of umbilical cord and late onset vascular accident at the narrow defect leading to ileal atresia may be missed in the prenatal diagnosis. The triad of exomphalos minor, Meckel's diverticulum and terminal ileal atresia secondary to antenatal strangulation of Littre's hernia is very rare to find in the same patient. A small exomphalos minor at the base of the umbilical cord can be missed even in the postnatal period. Our case lends direct evidence of vascular accident as a cause of ileal atresia and supports vascular theory. Whenever possible umbilicus should be preserved naturally and exomphalos sac should be opened higher up for excellent cosmetic results. PMID:23839617

  7. Topical Therapy for Mucosal Yeast Infections

    Microsoft Academic Search

    Paul R. Summers

    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

  8. Flagellin: key target of mucosal innate immunity

    Microsoft Academic Search

    M Vijay-Kumar; A T Gewirtz

    2009-01-01

    The mucosal immune system is charged with defending the host's vast interfaces with the outside world from the enormous and diverse group of microbes that colonizes these surfaces. A key means by which the mucosal immune system protects the host from such diverse microbes is using germ-line-encoded receptors that target structurally conserved motifs that mediate important bacterial functions. This review

  9. Mental Disorder and Psychologic Distress in Patients With Ulcerative Colitis After Ileal Pouch-Anal Anastomosis

    Microsoft Academic Search

    Winfried Häuser; Karl-Heinz Janke; Andreas Stallmach

    2005-01-01

    PURPOSE  The aim of this study was to determine if ileal pouch-anal anastomosis in patients with ulcerative colitis is a psychologic burden for patients, the frequency of mental disorders, the amount of psychologic distress, and their possible disease-related determinants. These factors were studied in patients with ulcerative colitis after ileal pouch anal anastomosis and were compared with ulcerative colitis patients without

  10. Proctocolectomy with jejunal pouch-distal rectal anastomosis: An alternative to ileal pouch reconstruction

    Microsoft Academic Search

    Michinaga Takahashi; James W. Williams; Keith A. Kelly

    1998-01-01

    The aim of this study was to determine whether a jejunal pouch would have a lower resting pressure, be more distensible, and\\u000a have more interdigestive migrating myoelectric complexes and less fecal bacterial overgrowth than would an ileal pouch after\\u000a proctocolectomy and pouch-distal rectal anastomosis. In six conscious dogs with a jejunal pouch-distal rectal anastomosis\\u000a and six with an ileal pouch-distal

  11. Extracellular glutathione fermentation using engineered Saccharomyces cerevisiae expressing a novel glutathione exporter.

    PubMed

    Kiriyama, Kentaro; Hara, Kiyotaka Y; Kondo, Akihiko

    2012-11-01

    A novel extracellular glutathione fermentation method using engineered Saccharomyces cerevisiae was developed by following three steps. First, a platform host strain lacking the glutathione degradation protein and glutathione uptake protein was constructed. This strain improved the extracellular glutathione productivity by up to 3.2-fold compared to the parental strain. Second, the ATP-dependent permease Adp1 was identified as a novel glutathione export ABC protein (Gxa1) in S. cerevisiae based on the homology of the protein sequence with that of the known human glutathione export ABC protein (ABCG2). Overexpression of this GXA1 gene improved the extracellular glutathione production by up to 2.3-fold compared to the platform host strain. Finally, combinatorial overexpression of the GXA1 gene and the genes involved in glutathione synthesis in the platform host strain increased the extracellular glutathione production by up to 17.1-fold compared to the parental strain. Overall, the metabolic engineering of the glutathione synthesis, degradation, and transport increased the total (extracellular + intracellular) glutathione production. The extracellular glutathione fermentation method developed in this study has the potential to overcome the limitations of the present intracellular glutathione fermentation process in yeast. PMID:22526809

  12. Digestibility measured by fecal and ileal collection in preruminant calves fed a clotting or a nonclotting milk replacer.

    PubMed

    Petit, H V; Ivan, M; Brisson, G J

    1989-01-01

    Eight Holstein male calves, each fitted with an ileal reentrant cannula at 7 to 10 d of age, were fed a milk replacer based on low heat skim milk powder with or without an oxalate-NaOH buffer known to prevent curd formation in the abomasum. The calves were used to study the effects of milk clotting on digesta flow at the ileum and apparent digestibility measured by fecal and ileal collection. Patterns of ileal flow of total digesta, DM, N, and fat were similar for the clotting and the nonclotting milk replacers. The apparent digestibility of DM and N was higher when measured by fecal than ileal collection for both milk replacers. Digestibility of DM was higher for the clotting than for the nonclotting milk replacer when measured by ileal collection. Clotting did not affect N digestibility measured by either fecal or ileal collection. The concentration of amino acids differed generally in the ileal digesta compared with concentration in feces. In the ileal digesta, some amino acids showed lower concentrations in the clotting milk replacer fed calves compared with those fed the nonclotting milk replacer. The coefficients of digestibility of each amino acid were similar when measured by either fecal or ileal collection. Clotting had no effect on amino acid digestibility measured by both fecal and ileal collection. The data suggest that fecal collection might indicate higher digestibility as compared with ileal collection and that the absence of milk replacer clotting does not affect ileal flow and digestibility of milk replacer N and fat. PMID:2925939

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

    PubMed Central

    1996-01-01

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

  14. 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

  15. 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.

  16. An African perspective on mucosal immunity and HIV1

    Microsoft Academic Search

    P Pala; V R Gomez-Roman; J Gilmour; P Kaleebu

    2009-01-01

    HIV prevention mandates an understanding of the mechanisms of mucosal immunity with attention to some unique features of the epidemic and mucosal environment in the developing world. An effective vaccine will have to induce mucosal protection against a highly diverse virus, which is equipped with a number of immune evasion strategies. Its development will require assessment of mucosal immune responses,

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

    2014-01-01

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

  19. The glutathione S-transferases of fish

    Microsoft Academic Search

    I. A. Nimmo

    1987-01-01

    Substantial soluble glutathione S-transferase activity and millimolar reduced glutathione (GSH) are present in most tissues of both teleosts and elasmobranchs. The hepatic enzymes of fish conjugate a range of electrophilic substrates with GSH, although their specificities are less broad than those of the transferases in rodent liver. There is no good evidence that fish transferases have ligandin-like activity or a

  20. [Clinical experience of ileal neobladder for bladder cancer].

    PubMed

    Miyoshi, S; Iwasaki, A; Inoue, H; Tsukikawa, M; Oka, D; Takao, T; Mizutani, S

    1998-01-01

    Between June 1993 and July 1996, an ileal neobladder was created in 20 patients after total cystectomy for bladder cancer. The mean post operative follow-up period was 32 months, with a range of 9 to 47 months. Ureteroileostomy was performed using the Le Duc-Camey procedure. There were 3 (15%) early postoperative complications, which were all of transient urine leakage from the neobladder. Late complications were encountered in 6 patients (30%), which were of stenosis of ureteroileal anastomosis in 2 (10%), stone in the neobladder in 2 (10%), neobladder-cutaneous fistula in 1 (5%) and neobladder-ureteral reflux in 1 (5%). Reoperation was necessary in 4 patients (20%); 2 for stenosis of ureteroileal anastomosis and 2 for removal of a stone in the neobladder. No urethral recurrence has been noted. Local recurrence occurred in 2 patients, who died of tumor progression 16 and 27 months postoperatively. All 20 patients were continent during the day time (100%), while 2 (10%) had nocturnal incontinence. PMID:9503200

  1. 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

  2. Stereochemistry of the microsomal glutathione S-transferase catalyzed addition of glutathione to chlorotrifluoroethene.

    PubMed

    Hargus, S J; Fitzsimmons, M E; Aniya, Y; Anders, M W

    1991-01-22

    The stereochemistry of S-(2-chloro-1,1,2-trifluoroethyl)glutathione formation was studied in rat liver cytosol, microsomes, N-ethylmaleimide-treated microsomes, 9000g supernatant fractions, purified rat liver microsomal glutathione S-transferase, and isolated rat hepatocytes. The absolute configuration of the chiral center generated by the addition of glutathione to chlorotrifluoroethene was determined by degradation of S-(2-chloro-1,1,2-trifluoroethyl)glutathione to chlorofluoroacetic acid, followed by derivatization to form the diastereomeric amides N-(S)-alpha-methylbenzyl-(S)-chlorofluoacetamide and N-(S)-alpha-methylbenzyl-(R)-chlorofluoroacetamide, which were separated by gas chromatography. Native and N-ethylmaleimide-treated rat liver microsomes, purified rat liver microsomal glutathione S-transferase, rat liver 9000g supernatant, and isolated rat hepatocytes catalyzed the formation of 75-81% (2S)-S-(2-chloro-1,1,2-trifluoroethyl)glutathione; rat liver cytosol catalyzed the formation of equal amounts of (2R)- and (2S)-S-(2-chloro-1,1,2-trifluoroethyl)glutathione. In rat hepatocytes, microsomal glutathione S-transferase catalyzed the formation of 83% of the total S-(2-chloro-1,1,2-trifluoroethyl)glutathione formed. These observations show that the microsomal glutathione S-transferase catalyzes the first step in the intracellular, glutathione-dependent bioactivation of the nephrotoxin chlorotrifluoroethene. PMID:1988059

  3. Primary mucosal melanoma: report of two cases.

    PubMed

    Karunakaran, Anila; Ravindran, Rathy; Shenoy, Mahesh; Arshad, Mohammed; Laxmi, M K Shruthi

    2013-01-01

    Primary mucosal malignant melanoma is of unusual occurrence and poor prognosis. We report two cases of primary mucosal melanoma, one in a 70-year-old male in the palate and the other in a 73-year-old female in the maxillary sinus. Early diagnosis and proper clinical and cytologic evaluation is necessary to institute therapeutic intervention. These cases are reported on account of their rarity of occurrence and difficulty of treatment. PMID:24858774

  4. Proctocolectomy with jejunal pouch-distal rectal anastomosis: an alternative to ileal pouch reconstruction.

    PubMed

    Takahashi, M; Williams, J W; Kelly, K A

    1998-01-01

    The aim of this study was to determine whether a jejunal pouch would have a lower resting pressure, be more distensible, and have more interdigestive migrating myoelectric complexes and less fecal bacterial overgrowth than would an ileal pouch after proctocolectomy and pouch-distal rectal anastomosis. In six conscious dogs with a jejunal pouch-distal rectal anastomosis and six with an ileal pouch-distal rectal anastomosis (controls), pouch distensibility and motility were measured using a barostat and perfused pressure-sensitive catheters passed per anum, pouch electrical activity was recorded using chronically implanted electrodes, and the number of bacteria per gram of stool was assessed by culture. Dogs with a jejunal pouch had lower resting pouch pressures, more distensible pouches, faster frequencies of pacesetter potentials in the pouch, more phase 3 intervals of the interdigesive migrating myoelectric complex reaching the pouch, but similar numbers and types of bacteria in their stools compared to the dogs with an ileal pouch. We concluded that jejunal pouches have a lower resting pressure, are more distensible, have more cleansing contractions, but a similar fecal flora compared to ileal pouches. A jejunal pouch has features that make it an attractive alternative to an ileal pouch for pouch-distal rectal or pouch-anal canal anastomosis after proctocolectomy. PMID:9841982

  5. Cluster analysis of genome-wide expression differences in disease-unaffected ileal mucosa in inflammatory bowel diseases

    Microsoft Academic Search

    Tianyi Zhang; Robert A. DeSimone; Hongyan Chen; Christina M Hamm; Jeffrey Yuan; Qing Qing Gong; Steven R. Hunt; Themistocles Dassopoulos; Rodney D. Newberry; Daniel N. Frank; Charles E. Robertson; Norman R. Pace; Erica Sodergren; George Weinstock; Xiangmin Jiao; Wei Zhu; Ellen Li

    2011-01-01

    Whole human genome (Agilent) expression profiling was conducted on disease-unaffected ileal RNA collected from the proximal margin of resected ileum from 47 ileal Crohn's disease (CD), 27 ulcerative colitis (UC) and 25 control patients without inflammatory bowel diseases (IBD). Cluster analysis combined with significance analysis of microarrays (SAM) and principal component analysis (PCA) and was used to reduce the data

  6. Combined terminal ileoscopy and biopsy is superior to small bowel follow-through in detecting terminal ileal pathology

    Microsoft Academic Search

    M. F Byrne; D. G Power; A. N Keeling; E Kay; F. E Murray; S. E Patchett

    2004-01-01

    Background. Several studies have compared small bowel barium examination with ileoscopy in assessment of terminal ileal disease. Some suggest that ileoscopy is superior in detection of terminal ileal disease whereas others suggest similar disease detection rates for both techniques.Aims. The aim of this retrospective study was to determine if small bowel follow-through and ileoscopy with terminal ileum biopsy compare favourably

  7. Canada’s first robotic-assisted totally intracorporeal orthotopic ileal neobladder

    PubMed Central

    Haddad, Richard L.; Richard, Patrick; Bladou, Franck

    2013-01-01

    Despite robotic-assisted radical cysto-prostatectomy being performed in several centres, the urinary diversion is most often performed extra-corporeal. A robotic intra-corporeal ileal neobladder is technically demanding and long-term functional outcome data is lacking. We performed a robotic intra-corporeal ileal neobladder in a 73-year-old man for muscle invasive non-metastatic bladder cancer. The total operative time was 6 hours 8 minutes. The estimated blood loss was 900 mL. There were no complications and he was discharged on day 12. The principles of open neobladder surgery were maintained, however key modifications were used to reduce technical difficulty and enable timely completion. We found that robotic intracorporeal ileal neobladder can be safely performed with an experienced robotic unit. PMID:24032066

  8. Image analysis in multisample biopsy after ileal pouch-anal anastomosis.

    PubMed

    Giarnieri, E; Giovagnoli, M R; Montesani, C; Nagar, C; Pronio, A M; Alderisio, M; Ribotta, G; Vecchione, A

    1996-01-01

    Pouchitis in ileal anal anastomosis represents an important clinical complication after restorative proctocolectomy. Acute and chronic inflammation of the reservoir is a frequent event sometimes associated with villous atrophy and colonic metaplasia. After ileal pouch anastomosis, twenty-one patients affected by ulcerative colitis were studied. An image analyzer CAS 200 (Becton Dickinson) was utilized to evaluate the DNA intranuclear content in every biopsy. In two cases abnormal DNA distribution was observed, and in one case a poliploid pattern was seen. Abnormal DNA distribution was also present in colonic metaplasia. Therefore, image analysis for the detection of DNA aneuploidy may be of additional value together with histologic parameters in follow up, in order to exclude transformation of the ileal mucosa in neoplastic epithelia. PMID:8920791

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

    PubMed

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

    2011-04-27

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

  10. 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.

  11. Cholera Toxins: Purification and Preliminary Characterization of Ileal Loop Reactive Type 2 Toxin

    PubMed Central

    Coleman, William H.; Kaur, Jasbir; Iwert, Marian E.; Kasai, George J.; Burrows, William

    1968-01-01

    Details for the preparation and partial purification of culture supernatant fluids of Vibrio cholerae (V. comma) 569B which retain rabbit ileal loop fluid-accumulating activity are presented. These preparations were fractionated on Sephadex G-200 and on diethylaminoethyl-Sephadex. On the latter, two fractions were obtained by elution with a linear sodium chloride gradient. The fraction designated “fraction I” retains the toxic activity as demonstrated in the rabbit ileal loop model. Chemical and immunological properties of this active fraction are described. Images PMID:4971885

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

    PubMed Central

    Mosi?ska, Paula; Fichna, Jakub; Storr, Martin

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. Transoral Mucosal Excision Sutured Gastroplasty

    PubMed Central

    Legner, Andras; Altorjay, Aron; Juhasz, Arpad; Stadlhuber, Rudolph; Reich, Viktor; Hunt, Brandon; Rothstein, Richard

    2014-01-01

    Introduction. An outpatient transoral endoscopic procedure for gastroesophageal reflux disease (GERD) and obesity would be appealing if safe, effective, and durable. We present the first in human experience with a new system. Methods. Eight patients with GERD (3) and obesity (5) were selected according to a preapproved study protocol. All GERD patients had preprocedure manometry and pH monitoring to document GERD as well as quality of life and symptom questionnaires. Obese patients (body mass index >35) underwent a psychological evaluation and tests for comorbidities. Under general anesthesia, a procedure was performed at the gastroesophageal junction including mucosal excision, suturing of the excision beds for apposition, and suture knotting. Results. One patient with micrognathia could not undergo the required preprocedural passage of a 60 F dilator and was excluded. The first 2 GERD patients had incomplete procedures due to instrument malfunction. The subsequent 5 subjects had a successfully completed procedure. Four patients were treated for obesity and had an average excess weight loss of 30.3% at 2-year follow-up. Of these patients, one had an 8-mm outlet at the end of the procedure recognized on video review—a correctable error—and another vomited multiple times postoperatively and loosened the gastroplasty sutures. The treated GERD patient had resolution of reflux-related symptoms and is off all antisecretory medications at 2-year follow-up. Her DeMeester score was 8.9 at 24 months. Conclusion. The initial human clinical experience showed promising results for effective and safe GERD and obesity therapy. PMID:24623807

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

    Microsoft Academic Search

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

    2006-01-01

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

  16. Divergent behavior of mucosal memory T cells.

    PubMed

    Pham, O H; McSorley, S J

    2015-07-01

    Memory CD4 T cells are strategically positioned at mucosal surfaces to initiate a robust adaptive immune response. The detection of specific antigen via the T-cell receptor causes these memory T cells to unleash a potent antimicrobial response that includes rousing local innate immune populations for tissue-specific defense. Paradoxically, these same memory T cells can also be stimulated by nonantigen-specific signals that are generated by the activity of local innate immune cells. This versatility of mucosal memory T cells in both the initiation and the sensing of local innate immunity could be a vitally important asset during pathogen defense but alternatively could be responsible for initiating and maintaining chronic inflammation in sensitive mucosal tissues. PMID:26059005

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

    PubMed

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

    2010-08-01

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

  18. Techniques and technologies to maximize mucosal exposure.

    PubMed

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

    2015-04-01

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

  19. An assessment of inflammation in the reservoir after restorative proctocolectomy with ileoanal ileal reservoir

    Microsoft Academic Search

    R. L. Moskowitz; N. A. Shepherd; R. J. Nicholls

    1986-01-01

    The significance of inflammation of the mucosa of the ileal reservoir after restorative proctocolectomy is not known although in some cases it appears to be associated with symptoms when the condition has been referred to as pouchitis. This investigation has aimed to determine the prevalence of inflammation, to define pouchitis and to examine some factors which might be related to

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

    Microsoft Academic Search

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

    1988-01-01

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

  1. The two-chamber ileal pelvic reservoir--an alternative design.

    PubMed

    Góes, R N; Fagundes, J J; Coy, C S; Amaral, C A; Peres, M A; Medeiros, R R

    1993-04-01

    A new ileal pouch design, combining an upper triplicate ileum with a lower duplicate ileum, is described. The physical characteristics of this two-chamber reservoir would lead to better functional results by delaying the filling time of the reservoir. PMID:8458270

  2. Digestibility of dried and toasted peas in pigs. 1. Ileal and total tract digestibilities of carbohydrates

    Microsoft Academic Search

    Nuria Canibe; K. E. Bach Knudsen

    1997-01-01

    The ileal and total tract digestibilities of carbohydrates were studied in pigs given diets containing dried or toasted peas (Pisum sativum var. Solara) as the sole source of polysaccharides. Peas from two different harvest years were fed to growing pigs fitted with a cannula at the end of the ileum in two experiments. Two types of cannulas were used in

  3. Sclerosing Mesenteritis With Occult Ileal Perforation: Report of a Case Simulating Extensive Intra-Abdominal Malignancy

    Microsoft Academic Search

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

    2004-01-01

    Sclerosing mesenteritis is a rare condition that is characterized by fibrosis affecting mainly small-bowel mesentery, which in extensive cases may mimic advanced intra-abdominal malignancy. Establishing the diagnosis in such cases is a clinical and histopathologic challenge. We report the successful management of a case of extensive sclerosing mesenteritis with occult ileal perforation, which was possibly the triggering cause. Severe complications

  4. Female Infertility After Ileal Pouch-Anal Anastomosis for Ulcerative Colitis

    Microsoft Academic Search

    Paul Johnson; Carole Richard; Anat Ravid; Leia Spencer; Eleanor Pinto; Mary Hanna; Zane Cohen; Robin McLeod

    2004-01-01

    PURPOSE: Although ulcerative colitis commonly affects young females, the impact of ulcerative colitis and its treatment on female fertility have not been well studied. The purpose of this survey was to examine the impact of ulcerative colitis and ileal pouch-anal anastomosis on female reproductive ability. METHODS: Demographic, reproductive history, and disease history information were obtained via a questionnaire mailed to

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

    PubMed

    Santoro, Sergio; de Aquino, Caio G Gaspar

    2015-08-01

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

  6. Age-dependent effects of t -BuOOH on glutathione disulfide reductase, glutathione peroxidase, and malondialdehyde in the brain

    Microsoft Academic Search

    Mei Ling Chang; Lori Klaidman; James D. Adams

    1995-01-01

    Intracerebroventriculart-butyl hydroperoxide has been reported to induce damage to many types of brain cells.t-Butyl hydroperoxide administration increases glutathione disulfide levels and decreases levels of glutathione. Young adult\\u000a mice may be more protected fromt-butyl hydroperoxide than mature mice due to their higher glutathione levels, even after the adminstration oft-butyl hydroperoxide. This leads to our current study, investigating glutathione peroxidase and glutathione

  7. 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

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

    PubMed Central

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

    2015-01-01

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

  9. Intestinal mucosal barrier function in health and disease

    Microsoft Academic Search

    Jerrold R. Turner

    2009-01-01

    Mucosal surfaces are lined by epithelial cells. These cells establish a barrier between sometimes hostile external environments and the internal milieu. However, mucosae are also responsible for nutrient absorption and waste secretion, which require a selectively permeable barrier. These functions place the mucosal epithelium at the centre of interactions between the mucosal immune system and luminal contents, including dietary antigens

  10. Palifermin for Oral Mucositis after Intensive Therapy for Hematologic Cancers

    Microsoft Academic Search

    Ricardo Spielberger; Patrick Stiff; William Bensinger; Teresa Gentile; Daniel Weisdorf; Tarun Kewalramani; Thomas Shea; Saul Yanovich; Keith Hansen; Stephen Noga; John McCarty; C. Frederick LeMaistre; Eric C. Sung; Bruce R. Blazar; Dieter Elhardt; Mon-Gy Chen; Christos Emmanouilides

    2009-01-01

    background Oral mucositis is a complication of intensive chemotherapy and radiotherapy with no ef- fective treatment. We tested the ability of palifermin (recombinant human keratinocyte growth factor) to decrease oral mucosal injury induced by cytotoxic therapy. methods This double-blind study compared the effect of palifermin with that of a placebo on the development of oral mucositis in 212 patients with

  11. Abiotic stress alters transcript profiles and activity of glutathione S-transferase, glutathione peroxidase, and glutathione reductase in Euphorbia esula.

    PubMed

    Anderson, James V.; Davis, David G.

    2004-03-01

    Glutathione S-transferase (GST), glutathione peroxidase (GPX), and glutathione reductase (GR) are enzymes that utilize glutathione to play an important role in plant defense mechanisms. In leafy spurge (Euphorbia esula L.), transcript and activity profiles for these enzymes are differentially influenced in tissue exposed to xenobiotic (diclofop-methyl) and environmental stress (cold and drought). Five different EeGST cDNA (including phi, tau, theta, and zeta class GSTs), one EeGPX cDNA, and one EeGR cDNA showed differential expression patterns in leafy spurge plants exposed to diclofop-methyl-, cold- and drought-stress. Tissue treated with diclofop-methyl also had increased GST, GPX and GR activities that were preceded or paralleled by increased gene expression. Transcript profiles resulting from drought-stressed plants were similar to transcript profiles from diclofop-methyl-treated plants but not cold-stressed plants. GPX activity in leafy spurge protein extracts was not bound to either S-hexylglutathione- or glutathione-agarose columns but instead co-migrated with fractions of GST activity that also were not bound by affinity chromatography. Fractions of GST proteins that were bound to S-hexylglutathione revealed that increased GST activity in diclofop-methyl-treated tissue could be identified as phi- and tau-type GSTs. PMID:15032839

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

    PubMed

    Soydan, Güray; Cekiç, Edip Güvenç; Tuncer, Meral

    2011-03-01

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

  13. Acetaldehyde does not inhibit glutathione peroxidase and glutathione reductase from mouse liver in vitro

    Microsoft Academic Search

    Lucinéia A. Pivetta; Alcir L. Dafre; Gilson Zeni; João B. T. Rocha; Marcelo Farina

    2006-01-01

    Acetaldehyde, the primary ethanol metabolite, has been implicated in the pathogenesis of alcoholic liver disease, but the mechanism involved is still under investigation. This study aims at the search for direct in vitro effects of different concentrations of acetaldehyde (30, 100 and 300?M) on the activities of glutathione reductase (GR), glutathione peroxidase (GPx) from liver supernatants, and the thiol-peroxidase activity

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

    PubMed Central

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

    2013-01-01

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

  15. Oral mucosal melanoma: a malignant trap

    Microsoft Academic Search

    Emmanouil K Symvoulakis; Dionysios E Kyrmizakis; Emmanouil I Drivas; Anastassios V Koutsopoulos; Stylianos G Malandrakis; Charalambos E Skoulakis; John G Bizakis

    2006-01-01

    Oral mucosal melanomas are highly malignant tumors. The 'chameleonic' presentation of a mainly asymptomatic condition, the rarity of these lesions, the poor prognosis and the necessity of a highly specialized treatment are factors that should be seriously considered by the involved health provider. We present the case of a 75-year-old man who was referred to the Ear, Nose and Throat

  16. Effect of ageing on colonic mucosal regeneration

    PubMed Central

    Sipos, Ferenc; Leiszter, Katalin; Tulassay, Zsolt

    2011-01-01

    The physiologic and pathologic cellular and molecular changes occurring with age in the human colon affect both the inflammatory process leading to mucosal injury and the regenerative capacity of the epithelium. On the one hand, age-related telomere shortening and inflamm-ageing may lead to the development of colonic inflammation, which results in epithelial damage. On the other hand, the altered migration and function of regenerative stem cells, the age-related methylation of mucosal healing-associated genes, together with the alterations of growth factor signaling with age, may be involved in delayed mucosal regeneration. The connections of these alterations to the process of ageing are not fully known. The understanding and custom-tailored modification of these mechanisms are of great clinical importance with regard to disease prevention and modern therapeutic strategies. Here, we aim to summarize the age-related microscopic and molecular changes of the human colon, as well as their role in altered mucosal healing. PMID:21799643

  17. Oral Mucositis: understanding the pathology and management

    PubMed Central

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

    2012-01-01

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

  18. Pediatric food allergy and mucosal tolerance

    Microsoft Academic Search

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

    2010-01-01

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

  19. Ultrasonic fragmentation. A new technique for mucosal proctectomy

    SciTech Connect

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

    1985-10-01

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

  20. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease

    PubMed Central

    Barnich, Nicolas; Carvalho, Frédéric A.; Glasser, Anne-Lise; Darcha, Claude; Jantscheff, Peter; Allez, Matthieu; Peeters, Harald; Bommelaer, Gilles; Desreumaux, Pierre; Colombel, Jean-Frédéric; Darfeuille-Michaud, Arlette

    2007-01-01

    The ileal mucosa of Crohn disease (CD) patients is abnormally colonized by adherent-invasive E. coli (AIEC) that are able to adhere to and invade intestinal epithelial cells. Here, we show that CD-associated AIEC strains adhere to the brush border of primary ileal enterocytes isolated from CD patients but not controls without inflammatory bowel disease. AIEC adhesion is dependent on type 1 pili expression on the bacterial surface and on carcinoembryonic antigen–related cell adhesion molecule 6 (CEACAM6) expression on the apical surface of ileal epithelial cells. We report also that CEACAM6 acts as a receptor for AIEC adhesion and is abnormally expressed by ileal epithelial cells in CD patients. In addition, our in vitro studies show that there is increased CEACAM6 expression in cultured intestinal epithelial cells after IFN-? or TNF-? stimulation and after infection with AIEC bacteria, indicating that AIEC can promote its own colonization in CD patients. PMID:17525800

  1. Effect of microbial phytase on apparent ileal amino acid digestibility of phosphorus-adequate diets in growing pigs

    Microsoft Academic Search

    So?a Nitrayová; Peter Patráš; Alexander Sommer; Jaroslav Heger

    2006-01-01

    Six ileally cannulated pigs (mean initial body weight 34.8 kg) were used to study the effect of microbial phytase on apparent ileal digestibility of P, total N and amino acids. Three P-adequate diets (digestible P concentration 2.3 g · kg ) containing barley (B), soyabean meal (S) or a mixture of the two (BS) with or without phytase supplement (1000 FTU · kg ) were fed

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

    PubMed Central

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

    2011-01-01

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

  3. Glutathione reductase is inhibited by acetaminophen-glutathione conjugate in vitro.

    PubMed

    Rousar, T; Parík, P; Kucera, O; Bartos, M; Cervinková, Z

    2010-01-01

    The aim of the present work was to investigate a new mechanism likely contributing to the toxic action of acetaminophen, especially to explore the possible inhibition of glutathione reductase through an acetaminophen-glutathione conjugate (APAP-SG). APAP-SG conjugate was synthesized by organic synthesis and purified by column chromatography. The inhibitory effect of the conjugate on two types of glutathione reductase (from yeasts and rat hepatocytes) was tested spectro-photometrically. We found that the enzyme activity was reduced similarly after the treatment with 2.96 mM acetaminophen-glutathione conjugate in both yeast and hepatocyte glutathione reductases (GR); the enzyme activity was inhibited to 52.7+/-1.5 % (2.4+/-0.3 mU/ml) in yeast GR (control activity was 5.6+/-0.3 mU/ml) and to 48.1+/-8.8 % (2.2+/-0.2 mU/ml) in rat hepatocytes lysate GR (control activity was 5.2+/-0.2 mU/ml). In addition, the enzyme activity (from hepatocytes lysate) was decreased to 79+/-7 %, 67+/-2 % and 39+/-7 %, in 0.37, 1.48 and 3.7 mM concentration of the conjugate, respectively. We found that glutathione reductase, the essential enzyme of the antioxidant system, was dose-dependently inhibited by the product of acetaminophen metabolism - the conjugate of acetaminophen and glutathione. PMID:19537930

  4. Glutathione S-Transferases in Pediatric Cancer

    PubMed Central

    Luo, Wen; Kinsey, Michelle; Schiffman, Joshua D.; Lessnick, Stephen L.

    2011-01-01

    The glutathione S-transferases (GSTs) are a family of ubiquitously expressed polymorphic enzymes important for detoxifying endogenous and exogenous compounds. In addition to their classic activity of detoxification by conjugation of compounds with glutathione, many other functions are now found to be associated with GSTs. The associations between GST polymorphisms/functions and human disease susceptibility or treatment outcome, mostly in adults, have been extensively studied and reviewed. This mini review focuses on studies related to GST epidemiology and functions related to pediatric cancer. Opportunities to exploit GST in pediatric cancer therapy are also discussed. PMID:22655244

  5. 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

  6. Induction of mucosal immune responses against a heterologous antigen fused to filamentous hemagglutinin after intranasal immunization with recombinant Bordetella pertussis.

    PubMed Central

    Renauld-Mongénie, G; Mielcarek, N; Cornette, J; Schacht, A M; Capron, A; Riveau, G; Locht, C

    1996-01-01

    Live vaccine vectors are usually very effective and generally elicit immune responses of higher magnitude and longer duration than nonliving vectors. Consequently, much attention has been turned to the engineering of oral pathogens for the delivery of foreign antigens to the gut-associated lymphoid tissues. However, no bacterial vector has yet been designed to specifically take advantage of the nasal route of mucosal vaccination. Herein we describe a genetic system for the expression of heterologous antigens fused to the filamentous hemagglutinin (FHA) in Bordetella pertussis. The Schistosoma mansoni glutathione S-transferase (Sm28GST) fused to FHA was detected at the cell surface and in the culture supernatants of recombinant B. pertussis. The mouse colonization capacity and autoagglutination of the recombinant microorganism were indistinguishable from those of the wild-type strain. In addition, and in contrast to the wild-type strain, a single intranasal administration of the recombinant strain induced both IgA and IgG antibodies against Sm28GST and against FHA in the bronchoalveolar lavage fluids. No anti-Sm28GST antibodies were detected in the serum, strongly suggesting that the observed immune response was of mucosal origin. This demonstrates, to our knowledge, for the first time that recombinant respiratory pathogens can induce mucosal immune responses against heterologous antigens, and this may constitute a first step toward the development of combined live vaccines administrable via the respiratory route. Images Fig. 1 Fig. 2 Fig. 3 PMID:8755582

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  9. Robotic assisted laparoscopic prostatectomy in men with proctocolectomy and restorative ileal pouch-anal anastomosis.

    PubMed

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

    2014-01-01

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

  10. Enterotoxigenicity of chicken isolates of Campylobacter jejuni in ligated ileal loops of rats.

    PubMed

    Saha, S K; Singh, N P; Sanyal, S C

    1988-06-01

    Ligated ileal loops in rats of the Charles-Foster strain, weighing 200-250 g and aged 7-8 months, provided a sensitive and reproducible means of testing the enterotoxigenicity of Campylobacter jejuni. All of 16 chicken isolates caused fluid accumulation comparable to that produced by toxigenic Vibrio cholerae O1, strain 569B. However, 11 of the isolates required one to three consecutive passages through the rat gut before doing so. The amount of fluid produced increased after each passage. Of three culture media tested, brucella broth of pH 6.7 supported the highest degree of enterotoxigenesis. Filtrates of cultures of all 16 chicken isolates in this medium were as effective as viable C. jejuni in producing fluid in ileal loops. The enterotoxin was neutralised completely by cholera antitoxin diluted 1 in 160, indicating its close immunobiological relationship to cholera toxin. PMID:3385766

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

    Microsoft Academic Search

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

    1996-01-01

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

  12. Development of a method for collection of ileal digesta in finishing pigs and determination of lysine availability in direct solvent cottonseed meal by chemical and chick growth assays 

    E-print Network

    Corley, Jimmie Ray

    1976-01-01

    cannula 23 Tissue out from body of cannula showing how proliferation allowed passage of digesta around cannula . . . . . . . . 23 (A) Aboral end of the transected ileum to be sutured to outside body wall. (B) Ileal anastomosis. (C) Folding of aboral... the stem of the cannula rested against the ileal wall. The ileal opening over the distal part of the intestinal tube was closed utilizing inverting suture pattern 9 with 00 chromic gut. A purse string suture was then placed around the stem...

  13. Enzyme-catalysed conjugations of glutathione with unsaturated compounds

    PubMed Central

    Boyland, E.; Chasseaud, L. F.

    1967-01-01

    1. Rat-liver supernatant catalyses the reaction of diethyl maleate with glutathione. 2. Evidence is presented that the enzyme involved is different from the known glutathione-conjugating enzymes, glutathione S-alkyltransferase, S-aryltransferase and S-epoxidetransferase. 3. Rat-liver supernatant catalyses the reaction of a number of other ??-unsaturated compounds, including aldehydes, ketones, lactones, nitriles and nitro compounds, with glutathione: separate enzymes may be responsible for these reactions. PMID:6035529

  14. The Mucosal B-Cell System

    Microsoft Academic Search

    Per Brandtzaeg; Finn-Eirik Johansen

    The mucosal B-cell system forms the adaptive basis for humoral immune defense of the extensive mucosae. Such antibody protection\\u000a depends on a complex cooperation between local B cells and secretory epithelia. Mucosa-associated lymphoid tissue (MALT) gives\\u000a rise to activated B cells with striking J-chain expression that are seeded to local and distant secretory effector sites.\\u000a Such homing is the biological

  15. Mucosal Immunity: from Allergy to Coeliac Disease

    Microsoft Academic Search

    Per Brandtzaeg

    During evolution, the mucosal immune system has developed two homeostatic mechanisms: (i) immune exclusion mediated by secretory\\u000a antibodies to control epithelial colonization of microorganisms and inhibit penetration of potentially dangerous substances;\\u000a and (ii) immunosuppression to counteract hypersensitivity against innocuous antigens such as allergens and most food proteins.\\u000a The latter mechanism is referred to as ‘oral tolerance’ when induced via the

  16. Research controversies in management of oral mucositis

    Microsoft Academic Search

    P. Biron; C. Sebban; R. Gourmet; G. Chvetzoff; I. Philip; J. Y. Blay

    2000-01-01

    The management of mucositis is the subject of many controversies, and the optimal treatment is still not known. Several evaluation\\u000a scoring systems have been described, but no one of these is appropriate to all clinical situations: a simple scale such as\\u000a that devised by the WHO can be used routinely, and more sophisticated ones can be implemented by trained experimenters

  17. Lung mucosal immunity: immunoglobulin-A revisited

    Microsoft Academic Search

    C. Pilette; Y. Ouadrhiri; V. Godding; J. P. Vaerman; Y. Sibille

    2001-01-01

    ABSTRACT: Mucosal,defence mechanisms,are critical in preventing colonization of the respiratory tract by pathogens,and penetration of antigens through the epithelial barrier. Recent research has now,illustrated the active contribution of the respiratory epithelium to the exclusion of microbes and particles, but also to the control of the inflammatory,and immune,responses in the airways and in the alveoli. Epithelial cells also mediate,the active transport

  18. Glubodies: randomized libraries of glutathione transferase enzymes

    Microsoft Academic Search

    Eugene W. Napolitano; Hugo O. Villar; Lawrence M. Kauvar; Deborah L. Higgins; Doug Roberts; Janis Mandac; Sandra K. Lee; Robert Bukar; Brenda L. Calio; John A. Tainer

    1996-01-01

    Background: The immunoglobulin framework has been mutagenized to engineer recombinant libraries of proteins as potential diagnostics and novel catalysts, although the often shallow binding cleft may limit the utility of this framework for binding diverse small organic molecules. By contrast, the glutathione S-transferase (GST) family of enzymes contains a deep binding cleft, which has evolved to accommodate a broad range

  19. Glutathione system in young spontaneously hypertensive rats.

    PubMed

    Lee, S K; Arunkumar, Sundaram; Sirajudeen, K N S; Singh, H J

    2010-12-01

    Glutathione (GSH) forms a part of the antioxidant system that plays a vital role in preventing oxidative stress, and an imbalance in the oxidant/antioxidant system has been linked to the pathogenesis of hypertension. The aim of this study was to investigate the status of the GSH system in the kidney of spontaneously hypertensive rats (SHR). Components of the GSH system, including glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), and total GSH content, were measured in the kidneys of 4, 6, 8, 12, and 16 weeks old SHR and Wistar-Kyoto (WKY) rats. Systolic blood pressure of SHR was significantly higher from the age of 6 weeks onwards compared with age-matched WKY rats. GPx activity in the SHR was significantly lower from the age of 8 weeks onwards when compared to that in age-matched WKY rats. No significant differences were evident in the GPx-1 protein abundance, and its relative mRNA levels, GR, GST activity, and total GSH content between SHR and age-matched WKY rats. The lower GPx activity suggests of an impairment of the GSH system in the SHR, which might be due to an abnormality in its protein rather than non-availability of a cofactor. Its role in the development of hypertension in SHR however remains unclear. PMID:20680541

  20. Role of glutathione in intracellular copper transport 

    E-print Network

    Ha, Chenxiang

    1994-01-01

    , is thought to play a crucial role in the regulation of this reactive ion. Using reversed phase HPLC, we have identified a glutathione-Cu complex in the acid-soluble fraction of cell extracts from human BeWo cells following treatment with 67CUC12. 67Cu...

  1. The Aedes aegypti glutathione transferase family

    Microsoft Academic Search

    Nongkran Lumjuana; Bradley J. Stevensona; Peter M. Brophyd; Brendan J. Loftuse; David W. Seversonf; Pembroke Palace

    In this report, we describe the glutathione transferase (GST) gene family in the dengue vector Aedes aegypti and suggest a novel role for a new class of mosquito GSTs. Twenty-six GST genes are present in Ae. aegypti, two of which are alternatively spliced to give a total of 29 transcripts for cytosolic GSTs. The six classes identified in other insect

  2. Influence of dietary peroxides, selenium and vitamin E on glutathione peroxidase of the gastrointestinal tract.

    PubMed

    Vilas, N N; Bell, R R; Draper, H H

    1976-05-01

    The influence of dietary peroxides, vitamin E and selenium on glutathione peroxidase (GSH-Px) activity in the gastrointestinal tract of the rat was investigated. Feeding 7% oxidized stripped corn oid (peroxide value 1,000) in a diet adequate in selenium and vitamin E increased the specific activity of GSH-Px in the stomach mucosa. Feeding oxidized oil produced an increase in the wet weight of the intestinal mucosa which was associated with a decrease in the specific activity of the enzyme. Total GSH-Px activity in the intestinal mucosa was unchanged or moderately increased. These changes were unaffected by the presence of vitamin E in the diet. Dietary peroxides had no effect on GSH-Px activity in the plasma or in the perirenal and paraepididymal adipose tissues. Subacute vitamin E deficiency had no consistent effect on the activity of the enzyme in several tissues examined. In rats fed a Se deficient diet glutathione peroxidase activity decreased markedly in most tissues but only slightly in the intestinal mucosa. The moderate decrease in the intestine may be explained by the accessibility of residual dietary Se to the mucosal cells. The role of Se in the detoxification of peroxides in foods and the response of gastrointestinal GSH-Px to dietary peroxides are discussed. PMID:1262968

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. Enterotoxigenicity of chicken isolates of Campylobacter jejuni in ligated ileal loops of rats

    Microsoft Academic Search

    S. K. Saha; N. P. Singh; S. C. Sanyal

    1988-01-01

    Summary. Ligated ileal loops in rats of the Charles-Foster strain, weighing 200-250 g and aged 7-8 months, provided a sensitive and reproducible means of testing the enterotoxigenicity of Campylobacter jejuni. All of 16 chicken isolates caused fluid accumulation comparable to that produced by toxigenic Vibrio cholerae 01, strain 569B. However, 11 of the isolates required one to three consecutive passages

  6. Use of absorbable staples for closure of proximal end of ileal loops.

    PubMed

    Wheeless, C R

    1986-02-01

    The use of the GIA stapler has reduced dramatically the operative time for the creation of urinary division ileal and colonic loops. It is widely known that steel staples in the urinary tract prompt stone formation around a foreign body. A case of stone formation around a GIA stainless steel staple is presented. A possible solution to this potential problem by the use of the new Polysorb-Lactimer absorbable TA55 stapler is presented. PMID:3511415

  7. 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-3?, 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-3? 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

  8. Biocide susceptibility and intracellular glutathione in Escherichia coli

    Microsoft Academic Search

    John S. Chapman; Megan A. Diehl; Richard C. Lyman

    1993-01-01

    Summary Inhibition of growth and speed of kill by biocides with different mechanisms of action was examined with respect to intracellular glutathione levels. strain deficient in intracellular glutathione was hypersusceptible to electrophilic biocides, with the exception of an isothiazolone biocide. Growth inhibition by quaternary ammonium compounds and radical-generating biocides was unaffected by intracellular glutathione levels. Speed of kill experiments demonstrated

  9. Interaction of the mycotoxin penicillic acid with glutathione and rat liver glutathione S-transferases

    Microsoft Academic Search

    Paul J. Dierickx; Jacques O. De Beer

    1984-01-01

    The in vitro interaction of the mycotoxin penicillic acid (PA) with rat liver glutathione S-transferase (GST) was studied using reduced glutathione and 1-chloro-2,4-dinitrobenzene as substrates. The inhibition of the GST activity by PA in crude extracts was dose dependent. Each of the different GST isoenzymes was inhibited, albeit at different degrees. Kinetic studies never revealed competitive inhibition kinetics. The conjugation

  10. Oxidized and reduced glutathione, ascorbate and glutathione reductase in matricaria recutita L. Callus cultures

    Microsoft Academic Search

    D. Podhradský; Eva ?ellárová; R. Hon?ariv

    1990-01-01

    In the long-term cultivated callus cultures ofMatricaria recutita L. the identical concentration changes in the biosynthesis of glutathione, glutamate, aspartate, total thiols and proteins\\u000a were detected within the subculture. The level of oxidized glutathione during the growth of callus culture was low with the\\u000a highest value 10.66 nmol g-1 on the 13th day of subculture. The ratio GSH\\/GSSG which significantly

  11. Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress.

    PubMed

    Hayes, J D; McLellan, L I

    1999-10-01

    Increases in the intracellular levels of reactive oxygen species (ROS), frequently referred to as oxidative stress, represents a potentially toxic insult which if not counteracted will lead to membrane dysfunction, DNA damage and inactivation of proteins. Chronic oxidative stress has numerous pathological consequences including cancer, arthritis and neurodegenerative disease. Glutathione-associated metabolism is a major mechanism for cellular protection against agents which generate oxidative stress. It is becoming increasingly apparent that the glutathione tripeptide is central to a complex multifaceted detoxification system, where there is substantial inter-dependence between separate component members. Glutathione participates in detoxification at several different levels, and may scavenge free radicals, reduce peroxides or be conjugated with electrophilic compounds. Thus, glutathione provides the cell with multiple defences not only against ROS but also against their toxic products. This article discusses how glutathione biosynthesis, glutathione peroxidases, glutathione S-transferases and glutathione S-conjugate efflux pumps function in an integrated fashion to allow cellular adaption to oxidative stress. Co-ordination of this response is achieved, at least in part, through the antioxidant responsive element (ARE) which is found in the promoters of many of the genes that are inducible by oxidative and chemical stress. Transcriptional activation through this enhancer appears to be mediated by basic leucine zipper transcription factors such as Nrf and small Maf proteins. The nature of the intracellular sensor(s) for ROS and thiol-active chemicals which induce genes through the ARE is described. Gene activation through the ARE appears to account for the enhanced antioxidant and detoxification capacity of normal cells effected by many cancer chemopreventive agents. In certain instances it may also account for acquired resistance of tumours to cancer chemotherapeutic drugs. It is therefore clear that determining the mechanisms involved in regulation of ARE-driven gene expression has enormous medical implications. PMID:10517533

  12. Disulphide bond formation by glutathione via the glutathione-trimethylamine- N-oxide complex

    NASA Astrophysics Data System (ADS)

    Brzezinski, Bogumil; Labowski, M.; Zundel, Georg

    1995-07-01

    Glutathione and its diethyl ester complexes (1 : 1) with trimethylamine N-oxide (TMAO) were studied by FTIR and 1H NMR spectrocopy. Immediately after mixing, complexes with strong SH⋯ON ? S -⋯H +ON hydrogen bonds are formed. They show large proton polarizability due to the fluctuation of the proton within these bonds. These complexes are, however, not stable since disulphide bonds are formed. Thus, TMAO regulates the disulphide bond formation in glutathione systems.

  13. Physiology of ileoanal anastomosis with ileal reservoir for ulcerative colitis and adenomatosis coli.

    PubMed

    Fiorentini, M T; Locatelli, L; Ceccopieri, B; Bertolino, F; Ostellino, O; Barlotta, A; Rolfo, P; Ferraris, R; de la Pierre, M; Dellepiane, M

    1987-04-01

    A physiologic and metabolic assessment was carried out on eight patients six months after total proctocolectomy with ileal reservoir for ulcerative colitis and familial adenomatosis coli. All patients were continent and able to defecate spontaneously, stool frequency ranging from two to five per 24 hours. Anal sphincter resting pressures (35 +/- 14 mmHg) and squeeze pressures (88 +/- 24.2 mmHg) were similar to those of a healthy population, with the exception of one patient's complaint of nocturnal mucous leakage per anus. Biopsies of the ileal mucosa of the reservoirs showed a mild inflammation in seven patients; in one a subtotal villous atrophy (plus glandular pattern) was found. Anthropometric measurements, lymphocyte counts, hemoglobin, albumin, transferrin, iron, B12, and folate were normal in all. In the majority of patients there was no evidence of bacterial overgrowth. Vitamin B12 absorption was reduced slightly in only one patient. Lipid absorption (as judged by the 14C-Triolein breath test) was abnormal in three patients. Fecal clearance of alpha 1 antitrypsin as protein losses index was abnormal in three patients. Bile acid malabsorption was the most important ileal dysfunction observed in the patients. PMID:3030677

  14. Purified g-Glutamyl Transpeptidases from Tomato Exhibit High Affinity for Glutathione and Glutathione S-Conjugates1

    Microsoft Academic Search

    Melinda Neal Martin; Janet P. Slovin

    2000-01-01

    g-Glutamyl transpeptidases (g GTases) are the only enzymes known to hydrolyze the unique N-terminal amide bonds of reduced glutathione (g-L-glutamyl-cysteinyl-glycine), oxidized glutathione, and glutathione S-conjugates. Two g GTases (I and II) with Km values for glutathione of 110 and 90 mM were purified 2,977-fold and 2,152-fold, respectively, from ripe tomato (Lycopersicon escu- lentum) pericarp. Both enzymes also hydrolyze dipeptides and

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

    Microsoft Academic Search

    B. Zechmann; M. Müller; G. Zellnig

    2006-01-01

    Summary.  The intracellular effects of GSH (reduced glutathione) and BSO (buthionine sulfoximine) treatment on glutathione content were\\u000a investigated with immunogold labeling in individual cellular compartments of Cucurbita pepo L. seedlings. Generally, GSH treatment led to increased levels of glutathione in roots and leaves (up to 3.5-fold in nuclei),\\u000a whereas BSO treatment significantly decreased glutathione content in all organs. Transmission electron microscopy

  16. Roles of M cells in infection and mucosal vaccines.

    PubMed

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

    2014-01-01

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

  17. Antibodies and Their Receptors: Different Potential Roles in Mucosal Defense

    PubMed Central

    Horton, Rachel E.; Vidarsson, Gestur

    2013-01-01

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

  18. Primary mucosal malignant melanoma of the oral cavity

    Microsoft Academic Search

    Arif Türkmen; Metin Temel; Mehmet Bekerecioglu

    Mucosal malignant melanoma arising from the head and neck region is a rare entity, and it is more aggressive than cutaneous\\u000a melanoma. Furthermore, the complex anatomy of the oral cavity makes complete surgical excision difficult. Thus, early diagnosis\\u000a and treatment of a mucosal lesion are important. In this study, three mucosal malignant melanoma cases and the literature\\u000a have been reviewed.

  19. Determination of picomole quantitites of hydroperoxides by a coupled glutathione peroxidase and glutathione disulfide specific glutathione reductase assay

    Microsoft Academic Search

    Kenneth G. D. Allen; Ching-Jang Huang; Catherine L. Morin

    1990-01-01

    A procedure to quantitate picomole amounts of hy- droperoxides based on GSSG formation is described. Hydroperoxides are incubated with GSH and glutathi- one peroxidase, and the GSSG formed is measured by a GSSG-specific glutathione reductase recycling assay. Prior to analysis the remaining GSH is removed with iV-ethylmaleimide. IV-Ethylmaleimide inhibition of the recycling assay is prevented by alkaline hydrolysis of the

  20. Effect of sucralfate on gastric mucosal blood flow in rats.

    PubMed Central

    Chen, B W; Hiu, W M; Lam, S K; Cho, C H; Ng, M M; Luk, C T

    1989-01-01

    Sucralfate possesses site protective and cytoprotective actions and heals ulcers effectively, but its effect on gastric mucosal blood flow is unknown. Using an ex vivo gastric chamber preparation, we studied the effect of sucralfate on gastric mucosal blood flow in rats by laser doppler flowmetry. Under both fasting and fed states, measurements of gastric mucosal blood flow and damage were made in rats after topical application of absolute ethanol alone or after pretreatment with sucralfate. Gastric mucosal damage was assessed by measuring the total area of haemorrhagic mucosal lesions. Ethanol induced gastric mucosal lesions were significantly less with sucralfate pretreatment than without (p less than 0.008). Mucosal blood flow significantly fell after ethanol application (p less than 0.001). The fall was significantly less in fed than in fasted rats (p less than 0.05), and after pretreatment with sucralfate 100 mg or 200 mg than without in both fasted (p less than 0.0008 and 0.00001, respectively) and fed (p less than 0.002 and 0.001, respectively) rats. Graded doses of sucralfate (25-400 mg) resulted in an increase in gastric mucosal blood flow in a dose dependent manner (r = 0.731, p less than 0.001). In conclusion that sucralfate increases gastric mucosal blood flow in rats and lessens the fall in blood flow in rats treated with ethanol, and this action may contribute to its protection against the vascular damage of mucosa by ethanol. PMID:2599440

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

    We have previously shown that high-protein (HP) diet ingestion causes marked changes in the luminal environment of the colonic epithelium. This study aimed to evaluate the impact of such modifications on small intestinal and colonic mucosa, two segments with different transit time and physiological functions. Rats were fed with either normal protein (NP; 14% protein) or HP (53% protein) isocaloric diet for 2 weeks, and parameters related to intestinal mucous-secreting cells and to several innate/adaptive immune characteristics (myeloperoxidase activity, cytokine and epithelial TLR expression, proportion of immune cells in gut-associated lymphoid tissues) were measured in the ileum and colon. In ileum from HP animals, we observed hyperplasia of mucus-producing cells concomitant with an increased expression of Muc2 at both gene and protein levels, reduction of mucosal myeloperoxidase activity, down-regulation of Tlr4 gene expression in enterocytes and down-regulation of mucosal Th cytokines associated with CD4+ lymphocyte reduction in mesenteric lymph nodes. These changes coincided with an increased amount of acetate in the ileal luminal content. In colon, HP diet ingestion resulted in a lower number of goblet cells at the epithelial surface but increased goblet cell number in colonic crypts together with an increased Muc3 and a slight reduction of Il-6 gene expression. Our data suggest that HP diet modifies the goblet cell distribution in colon and, in ileum, increases goblet cell activity and decreases parameters related to basal gut inflammatory status. The impact of HP diet on intestinal mucosa in terms of beneficial or deleterious effects is discussed. PMID:25459886

  3. Glutathione and redox signaling in substance abuse

    PubMed Central

    Uys, Joachim D.; Mulholland, Patrick J.; Townsend, Danyelle M.

    2015-01-01

    Throughout the last couple decades, the cause and consequences of substance abuse has expanded to identify the underlying neurobiological signaling mechanisms associated with addictive behavior. Chronic use of drugs, such as cocaine, methamphetamine and alcohol leads to the formation of oxidative or nitrosative stress (ROS/RNS) and changes in glutathione and redox homeostasis. Of importance, redox-sensitive post-translational modifications on cysteine residues, such as S-glutathionylation and S-nitrosylation could impact on the structure and function of addiction related signaling proteins. In this commentary, we evaluate the role of glutathione and redox signaling in cocaine-, methamphetamine- and alcohol addiction and conclude by discussing the possibility of targeting redox pathways for the therapeutic intervention of these substance abuse disorders. PMID:25027386

  4. Glutathione and redox signaling in substance abuse.

    PubMed

    Uys, Joachim D; Mulholland, Patrick J; Townsend, Danyelle M

    2014-07-01

    Throughout the last couple decades, the cause and consequences of substance abuse has expanded to identify the underlying neurobiological signaling mechanisms associated with addictive behavior. Chronic use of drugs, such as cocaine, methamphetamine and alcohol leads to the formation of oxidative or nitrosative stress (ROS/RNS) and changes in glutathione and redox homeostasis. Of importance, redox-sensitive post-translational modifications on cysteine residues, such as S-glutathionylation and S-nitrosylation could impact on the structure and function of addiction related signaling proteins. In this commentary, we evaluate the role of glutathione and redox signaling in cocaine-, methamphetamine- and alcohol addiction and conclude by discussing the possibility of targeting redox pathways for the therapeutic intervention of these substance abuse disorders. PMID:25027386

  5. Competitive and non-competitive antagonism exhibited by 'selective' antagonists at atrial and ileal muscarinic receptor subtypes.

    PubMed Central

    Eglen, R. M.; Whiting, R. L.

    1987-01-01

    The affinity of a number of 'selective' agonists and antagonists has been assessed at atrial or ileal muscarinic receptors by use of in vitro functional analysis. The most selective compound for ileal muscarinic receptors was silabenzhexol (approx. 50 fold), and to a lesser extent benzhexol (approx. 5 fold). Conversely, the most selective compound for the atrial muscarinic receptors was AF-DX 116 (approx. 6 fold). The novel M1-receptor antagonist, telenzepine and other antagonists such as propantheline and isopropamide did not distinguish between atrial and ileal receptors. Dicyclomine, adiphenine, hexahydroadiphenine and oxyphenonium exhibited competitive antagonism at atrial receptors but non-competitive antagonism at ileal receptors. No conclusions could, therefore, be drawn with regard to their selectivity. The agonists, arecaidine propargyl ester (APE), ethoxyethyltriethylammonium (EOE) and carbachol, exhibited some selectivity in potency but little difference in affinity. It is concluded that the study supports the existence of ileal and atrial muscarinic receptor subtypes. However, the use of dicyclomine and related compounds in receptor classification is limited. PMID:3580704

  6. Ipilimumab for patients with advanced mucosal melanoma.

    PubMed

    Postow, Michael A; Luke, Jason J; Bluth, Mark J; Ramaiya, Nikhil; Panageas, Katherine S; Lawrence, Donald P; Ibrahim, Nageatte; Flaherty, Keith T; Sullivan, Ryan J; Ott, Patrick A; Callahan, Margaret K; Harding, James J; D'Angelo, Sandra P; Dickson, Mark A; Schwartz, Gary K; Chapman, Paul B; Gnjatic, Sacha; Wolchok, Jedd D; Hodi, F Stephen; Carvajal, Richard D

    2013-06-01

    The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded. Available peripheral blood samples were used to assess humoral immunity against a panel of cancer-testis antigens and other antigens. By the immune-related response criteria of the 30 patients who underwent radiographic assessment after ipilimumab at approximately week 12, there were 1 immune-related complete response, 1 immune-related partial response, 6 immune-related stable disease, and 22 immune-related progressive disease. By the modified World Health Organization criteria, there were 1 immune-related complete response, 1 immune-related partial response, 5 immune-related stable disease, and 23 immune-related progressive disease. Immune-related adverse events (as graded by Common Terminology Criteria for Adverse Events version 4.0) consisted of six patients with rash (four grade 1, two grade 2), three patients with diarrhea (one grade 1, two grade 3), one patient with grade 1 thyroiditis, one patient with grade 3 hepatitis, and 1 patient with grade 2 hypophysitis. The median overall survival from the time of the first dose of ipilimumab was 6.4 months (range: 1.8-26.7 months). Several patients demonstrated serologic responses to cancer-testis antigens and other antigens. Durable responses to ipilimumab were observed, but the overall response rate was low. Additional investigation is necessary to clarify the role of ipilimumab in patients with mucosal melanoma. PMID:23716015

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

    E-print Network

    Li, Adrienne V.

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

  8. The effect of fumaric acid and sodium fumarate supplementation to diets for weanling pigs on amino acid digestibility and volatile fatty acid concentrations in ileal digesta

    Microsoft Academic Search

    V. M. Gabert; W. C. Sauer

    1995-01-01

    An experiment was carried out with 12 Camborough × Canabrid barrows to determine the effect of fumaric acid (FA) and sodium fumarate (NaFA) supplementation of the diet on the apparent ileal digestibility coefficients of amino acids and the concentrations of volatile fatty acids in ileal digesta. The pigs were weaned at 28 days of age (initial and final body weights

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

    Microsoft Academic Search

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

    2005-01-01

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

  10. Mucosal Immunosenescence in the Gastrointestinal Tract: A Mini-Review.

    PubMed

    Sato, Shintaro; Kiyono, Hiroshi; Fujihashi, Kohtaro

    2015-01-01

    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 the 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 targeting have been shown to be attractive and effective immunological strategies. Similarly, microfold (M) cells involved in the antigen (Ag) uptake 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. © 2014 S. Karger AG, Basel. PMID:25531743

  11. Psittacid herpesviruses associated with mucosal papillomas in neotropical parrots

    Microsoft Academic Search

    Darrel K Styles; Elizabeth K Tomaszewski; Laurie A Jaeger; David N Phalen

    2004-01-01

    Mucosal papillomas are relatively common lesions in several species of captive neotropical parrots. They cause considerable morbidity and in some cases, result in mortality. Previous efforts to identify papillomavirus DNA and proteins in these lesions have been largely unsuccessful. In contrast, increasing evidence suggests that mucosal papillomas may contain psittacid herpesviruses (PsHVs). In this study, 41 papillomas from 30 neotropical

  12. Oral mucosal status and major salivary gland function

    Microsoft Academic Search

    A. Wolff; P. C. Fox; J. A. Ship; J. C. Atkinson; A. A. Macynski; B. J. Baum

    1990-01-01

    Normal salivary function is considered to be critical for the maintenance of healthy oral mucosa. However, few studies have examined mucosal changes in patients with objectively documented salivary gland performance. In the present report, the mucosal status of 298 subjects being evaluated in a dry mouth clinic was assessed. A complete oral examination was performed and unstimulated and stimulated salivary

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

    E-print Network

    Paris-Sud XI, Université de

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

  14. 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 ?-adrenergic fibres that are involved with vasoconstriction. Dexmedetomidine is a sedative and analgesic agent that acts through the ?-2 adrenoceptor, and is expected to have a vasoconstrictive action in the oral cavity. We have focused on the relation between the effects of ?-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 ?g/kg/h for 10 min and a continuous infusion of 0.7 ?g/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 ?-2 adrenoceptors. PMID:23958351

  15. Canine oral mucosal mast cell tumours.

    PubMed

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

    2013-11-11

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

  16. Modulation of ileal apical Na+-dependent bile acid transporter ASBT by protein kinase C

    PubMed Central

    Sarwar, Zaheer; Annaba, Fadi; Dwivedi, Alka; Saksena, Seema; Gill, Ravinder K.; Alrefai, Waddah A.

    2009-01-01

    Ileal apical Na+-dependent bile acid transporter (ASBT) is responsible for reabsorbing the majority of bile acids from the intestinal lumen. Rapid adaptation of ASBT function in response to physiological and pathophysiological stimuli is essential for the maintenance of bile acid homeostasis. However, not much is known about molecular mechanisms responsible for acute posttranscriptional regulation of ileal ASBT. The protein kinase C (PKC)-dependent pathway represents a major cell signaling mechanism influencing intestinal epithelial functions. The present studies were, therefore, undertaken to investigate ASBT regulation in intestinal Caco-2 monolayers by the well-known PKC activator phorbol 12-myristate 13-acetate (PMA). Our results showed that Na+-dependent [3H]taurocholic acid uptake in Caco-2 cells was significantly inhibited in response to 2 h incubation with 100 nM PMA compared with incubation with 4?-PMA (inactive form). The inhibitory effect of PMA was blocked in the presence of 5 ?M bisindolylmaleimide I (PKC inhibitor) but not 1,2-bis(2-aminophenoxy)ethane-N,N,N?,N?-tetraacetic acid-AM (Ca2+ chelator) or LY-294002 (phosphatidylinositol 3-kinase inhibitor). PMA inhibition of ASBT function was also abrogated in the presence of myristoylated PKC? pseudosubstrate peptide, indicating involvement of the atypical PKC? isoform. The inhibition by PMA was associated with a significant decrease in the maximal velocity of the transporter and a reduction in ASBT plasma membrane content, suggesting a modulation by vesicular recycling. Our novel findings demonstrate a posttranscriptional modulation of ileal ASBT function and membrane expression by phorbol ester via a PKC?-dependent pathway. PMID:19571234

  17. Patient-posture and Ileal-intubation during colonoscopy (PIC): a randomized controlled open-label trial

    PubMed Central

    Ahammed, Sk Mahiuddin; Das, Kshaunish; Sarkar, R.; Dasgupta, J.; Bandopadhyay, S.; Dhali, G. K.

    2014-01-01

    Background and aims: Patient’s posture change is commonly employed by a colonoscopist to achieve complete examination. We studied whether patient’s posture (left-lateral decubitus vs supine) influenced the success rate of ileal intubation. Patients and methods: In this prospective open-label randomized study performed in the Endoscopy Suite of a tertiary-care center, all adult outpatients referred for colonoscopy, in whom cecal intubation was achieved and who satisfied predefined inclusion criteria, were randomized to undergo ileal intubation in either of the above two postures. Colonoscopy (EC-201 WL, Fujinon) was performed after overnight poly-ethylene-glycol preparation, under conscious sedation and continuous pulse-oxymetry monitoring. After confirming cecal intubation, patients were randomized for ileal intubation. Success was defined by visualization of ileal mucosa or villi (confirmed by digital photography) and was attempted until limited by pain and/or time of ??6?min. Results: Of 320 eligible patients, 217 patients (150 males) were randomized, 106 to left-lateral decubitus and 111 to supine posture. At baseline, the two groups were evenly matched. Successful ileal intubation was achieved in 145 (66.8?%) patients overall, significantly higher in the supine posture (74.8?% versus 58.5?%; P?=?0.014). On multivariate analysis, supine posture (P?=?0.02), average/good right-colon preparation (P?ileal findings were recorded in 13 (9?%) patients. Conclusion: Ileoscopy is more successful in supine than in left-lateral decubitus posture. Age, bowel preparation and type of IC valve also determine success.

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

    PubMed

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

    2008-06-01

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

  19. Ileal duplication: an unusual cause of intestinal obstruction in adult life.

    PubMed

    Barbosa, L; Soares, C; Póvoa, A A; Maciel, J P

    2015-01-01

    Gastrointestinal duplications are rare congenital malformations seldom diagnosed in adulthood. They may vary greatly in size and location, with the small intestine being their major focus. Their clinical presentation is widely variable and unspecific, mimicking more common pathologies, thus making preoperative diagnosis very difficult. The intraoperative surgeon's experience and knowledge are crucial in recognising these lesions so that they can be correctly managed. In this report, the authors present a case of a 36-year-old man with an acute intestinal obstruction as the first presentation of ileal duplication. PMID:26055580

  20. Enterotoxigenicity of human and animal isolates of Campylobacter jejuni in ligated rat ileal loops.

    PubMed

    Chattopadhyay, U K; Rathore, R S; Pal, D; Das, M S

    1991-03-01

    Human and animal isolates of Campylobacter jejuni were tested for enterotoxigenicity in ligated loop of Charles-Foster rats. Of 21 isolates, 13 were proved to be toxin-positive in the initial experiments. However, the remaining 8 required one to three passages through the rat ileal loop before showing the capacity to produce enterotoxin. All isolates caused fluid accumulation comparable with the amount produced by the standard toxigenic strain of Vibrio cholerae 01 1naba 569B. The isolates of C. jejuni from human and animal sources did not show any quantitative difference in their capacity to produce enterotoxin. PMID:1869798

  1. Dietary electrolyte balance influences ileal endogenous amino acid losses in broiler chickens.

    PubMed

    Adedokun, S A; Applegate, T J

    2014-04-01

    The objective of the current study was to determine the effect of nitrogen-free diets formulated with 2 ratios of corn starch and dextrose and 2 levels of dietary electrolyte balance (DEB; calculated as Na + K - Cl(-), in mEq/kg of diet) on ileal endogenous amino acid (EAA) losses in 48-d-old broiler chickens. On d 43, 240 broiler chickens were allotted to 4 dietary treatments with 6 replicate cages per diet in a completely randomized design. Each experimental diet was fed for 5 d (d 43-48). All diets were free of nitrogen with 2 ratios of corn starch-to-dextrose (0.31 and 1.04) and 2 levels of DEB (108 and 219 mEq/kg of diet). Final BW and BW loss between birds fed the 2 corn starch-to-dextrose ratios and between birds fed 2 levels of DEB were not different (P > 0.05). Birds fed the diet containing a high level of DEB consumed less (P < 0.05) feed than birds on the low-DEB diet. Birds on the high-corn starch-to-dextrose (1.04) diet showed a tendency for higher (P = 0.08) feed intake. High dietary dextrose level (corn starch-to-dextrose ratio of 0.31) resulted in higher (P < 0.05) ileal DM and energy digestibility. A high level of DEB resulted in higher (P < 0.05) ileal endogenous nitrogen loss. Arginine, Ile, Leu, Phe, Val, Ala, Glu, Gly, Pro, and Tyr secretion into the gut increased (P ? 0.05) with an increasing level of DEB. Endogenous His, Lys, Thr, Asp, Cys, and Ser showed a tendency for increased (P ? 0.1) losses with a high level of DEB. Mean ileal EAA losses for the indispensable and dispensable amino acids for the low-DEB diet were 81 and 82%, respectively, that of the birds fed the high-DEB diet. The 4 amino acids with the lowest endogenous flow were Met, His, Tyr, and Cys, whereas the highest endogenous flow was found in Glu, Asp, Val, and Leu. Data from the current study showed that EAA losses in the ileum of broiler chickens are significantly affected by DEB, but not by the ratio of corn starch to dextrose. PMID:24706971

  2. 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

  3. Glutathione Reductase: A Putative Redox Regulatory System in Plant Cells

    Microsoft Academic Search

    A. S. V. Chalapathi Rao; Attipalli R. Reddy

    Glutathione reductase (GR, EC 1.6.4.2) and glutathione (GSH, ?-Glu-Cys-Gly) are important components of the cell’s scavenging\\u000a system for reactive oxygen compounds in plants. GSH is a major reservoir of nonprotein reduced sulfur. In addition, GSH plays\\u000a a crucial role in cellular defense, where it gets oxidized to glutathione disulfide (GSSG). GR mediates the reduction of GSSG\\u000a to GSH by using

  4. Plant glutathione biosynthesis: diversity in biochemical regulation and reaction products.

    PubMed

    Galant, Ashley; Preuss, Mary L; Cameron, Jeffrey C; Jez, Joseph M

    2011-01-01

    In plants, exposure to temperature extremes, heavy metal-contaminated soils, drought, air pollutants, and pathogens results in the generation of reactive oxygen species that alter the intracellular redox environment, which in turn influences signaling pathways and cell fate. As part of their response to these stresses, plants produce glutathione. Glutathione acts as an anti-oxidant by quenching reactive oxygen species, and is involved in the ascorbate-glutathione cycle that eliminates damaging peroxides. Plants also use glutathione for the detoxification of xenobiotics, herbicides, air pollutants (sulfur dioxide and ozone), and toxic heavy metals. Two enzymes catalyze glutathione synthesis: glutamate-cysteine ligase, and glutathione synthetase. Glutathione is a ubiquitous protective compound in plants, but the structural and functional details of the proteins that synthesize it, as well as the potential biochemical mechanisms of their regulation, have only begun to be explored. As discussed here, the core reactions of glutathione synthesis are conserved across various organisms, but plants have diversified both the regulatory mechanisms that control its synthesis and the range of products derived from this pathway. Understanding the molecular basis of glutathione biosynthesis and its regulation will expand our knowledge of this component in the plant stress response network. PMID:22645536

  5. ORIGINAL PAPER Glutathione peroxidase inhibitory assay for electrophilic

    E-print Network

    Nizkorodov, Sergey

    the inhibition of glutathione peroxidase 1 (GPx-1) by organic electrophilic pollutants, such as acrolein concentrations of highly reactive electrophilic chemicals (including acrolein, glyoxal, methylglyoxal, and p

  6. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  7. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

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

    EPA Science Inventory

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

  9. Head and neck mucosal melanoma: a review.

    PubMed

    Lourenço, Silvia V; Fernandes, Juliana D; Hsieh, Ricardo; Coutinho-Camillo, Claudia M; Bologna, Sheyla; Sangueza, Martin; Nico, Marcello M S

    2014-07-01

    Head and neck mucosal melanoma (MM) is an aggressive and rare neoplasm of melanocytic origin. To date, few retrospective series and case reports have been reported on MM. This article reviews the current evidence on head and neck MM and the molecular pathways that mediate the pathogenesis of this disease. Head and neck MM accounts for 0.7%-3.8% of all melanomas and involve (in decreasing order of frequency) the sinonasal cavity, oral cavity, pharynx, larynx, and upper esophagus. Although many studies have examined MM of the head and neck and the underlying molecular pathways, individual genetic and molecular alterations were less investigated. Further studies are needed to complement existing data and to increase our understanding of melanocytes tumorigenesis. PMID:24423929

  10. Helminthic therapy: improving mucosal barrier function

    PubMed Central

    Wolff, Martin J.; Broadhurst, Mara J.

    2014-01-01

    The epidemiology of autoimmune diseases and helminth infections led to suggestions that helminths could improve inflammatory conditions, which was then tested using animal models. This has translated to clinical investigations aimed at the safe and controlled reintroduction of helminthic exposure to patients suffering from autoimmune diseases (so-called “helminthic therapy”) in an effort to mitigate the inflammatory response. In this review, we will summarize the results of recent clinical trials of helminthic therapy, with particular attention to mechanisms of action. Whereas previous reviews have emphasized immune regulatory mechanisms activated by helminths, we propose that enhancement of mucosal barrier function may have an equally important role in improving conditions of inflammatory bowel diseases. PMID:22464690

  11. Histamine and gut mucosal immune regulation.

    PubMed

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

    2014-03-01

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

  12. Effect of Exogenous Glutathione, Glutathione Reductase, Chlorine Dioxide, and Chlorite on Osmotic Fragility of Rat Blood In Vitro

    Microsoft Academic Search

    M. S. Abdel-Rahman; D. Couri; R. J. Bull

    1984-01-01

    Chlorine dioxide (CIO2), chlorite (CIO-2), and chlorate (CIO-3) in drinking water decreased blood glutathione and RBC osmotic fragility in vivo. The osmotic fragility and glutathione content were also studied in rat blood treated with CIO2, CIO-2, CIO-3 in vitro. RBC hemolysis was decreased in rat blood after 30, 60, and 120 minutes by all treatments. The glutathione content expressed as

  13. Conjugation of isoprene monoepoxides with glutathione, catalyzed by ?, ?, ? and ?-class glutathione S-transferases of rat and man

    Microsoft Academic Search

    Jan J. P Bogaards; Joke C Venekamp; Florence G. C Salmon; Peter J van Bladeren

    1999-01-01

    In the present study, the enzymatic conjugation of the isoprene monoepoxides 3,4 epoxy-3-methyl-1-butene (EPOX-I) and 3,4-epoxy-2-methyl-1-butene (EPOX-II) with glutathione was investigated, using purified glutathione S-transferases (GSTs) of the ?, ?, ? and ?-class of rat and man. HPLC analysis of incubations of EPOX-I and EPOX-II with [35S]glutathione (GSH) showed the formation of two radioactive fractions for each isoprene monoepoxide. The

  14. Oral mucosal status and major salivary gland function

    SciTech Connect

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

    1990-07-01

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

  15. Is there a place for ileal pouch-anal anastomosis in patients with Crohn's colitis?

    PubMed

    Panis, Y

    1998-12-01

    It is generally agreed that ileal pouch-anal anastomosis (IPAA) is contraindicated in patients with Crohn's disease (CD), since recurrent disease will frequently necessitate pouch excision, thereby fostering to the ultimate development of a short bowel syndrome. For these reasons, patients with CD requiring coloproctectomy have up till now undergone definitive end ileostomy. However, when faced with the prospect of definitive ileostomy in young patients, the possibility to keep, even for a few years before the disease recurs, acceptable continence and defecation must be stressed. Although the failure rate is higher in patients with CD than in patients with ulcerative colitis, long-term results from recent reports, as well as from our own experience, demonstrated that in selected patients with CD (i.e. without anoperineal or ileal manifestations), pouch can be maintain in function in 55 to 90% of the patients. In these patients functional results are similar to those of patients with ulcerative colitis. In conclusion, unlike the authors who consider that IPPA is definitely contraindicated in CD, we believe that IPAA could be proposed for selected patients with CD for whom rectal resection is mandatory, as an alternative to coloproctectomy with definitive end ileostomy. The patients concerned are those with no history of anal manifestations and no evidence of small bowel involvement. PMID:9883014

  16. Study of antireflux nipple valves of Kock ileal urinary reservoir. Experimental investigation in dogs.

    PubMed

    Boyd, S D; Skinner, D G; Lieskovsky, G; Kawachi, M H; Ahlering, T E

    1991-01-01

    To better assess the construction, maintenance, and function of the Kock ileal urinary reservoir with its continent antirefluxing nipple valves, laboratory investigations in dogs were done simultaneously with clinical trials in humans in 1983. Fifteen dogs underwent creation of hemi-Kock ileal reservoirs (without the efferent valve and limb) that were anastomosed to their bladders as enterocystoplasties. The afferent antirefluxing nipple valves were intussuscepted after 7 cm of underlying mesentery had been removed. The nipples were further stabilized with metal and absorbable (Polysorb) staples and Marlex collars. The right ureters were anastomosed to the afferent limb of the reservoirs with the contralateral systems left intact as controls. Ten dogs were able to be followed at the vivaria for twelve to thirty-six months and then studied. All nipple valves remained intact, viable, and nonrefluxing without revision. All kidneys remained histologically normal except those in dogs with dilated ureters secondary to ureteroileal stenosis with concurrent calculi formation. Calculi formed on exposed metal staples and Marlex. The absorbable staples were found to promote appropriate healing and were never the nidus for stone formation. It appears that the intussuscepted nipple valve (with its mesentery removed) is reproducible and functionally reliable in preventing reflux. It also appears these valves can histologically preserve diverted kidneys if the upper urinary tract drainage is normal and calculi are minimized. The proper placement of staples and the elimination of Marlex-anchoring collars are indicated to minimize calculi. PMID:1986481

  17. Effects of ileal resection on biliary lipids and bile acid composition in patients with Crohn's disease.

    PubMed Central

    Lapidus, A; Einarsson, K

    1991-01-01

    Biliary lipid composition, cholesterol saturation, and bile acid pattern were determined in fasting duodenal bile of 10 patients (four men and six women, mean age 41 years) with Crohn's disease and a history of ileal resection (mean 64 cm). The data were compared with corresponding values in a group of healthy subjects. None of the patients with Crohn's disease had supersaturated bile. Cholesterol saturation was significantly lower in the patients with Crohn's disease than in the healthy subjects. The molar percentage of cholesterol was also lower among the patients but there was no significant difference. The molar percentages of phospholipids and bile acids were normal. Bile acid composition in the patients with ileal resection was characterised by a significant decrease in the deoxycholic acid fraction and a pronounced increase in the ursodeoxycholic acid fraction compared with the healthy subjects. The surprisingly high percentage of ursodeoxycholic acid may contribute to the low degree of cholesterol saturation in bile. Based on these results patients with Crohn's disease should not have an increased risk of cholesterol gall stone formation. PMID:1773954

  18. Effects of Hulls of Faba Beans (Vicia faba L.) with a Low or High Content of Condensed Tannins on the Apparent Ileal and Fecal Digestibility of Nutrients and the Excretion of Endogenous Protein in Ileal Digesta and Feces of Pigs

    Microsoft Academic Search

    A. J. M. Jansman; M. W. A. Verstegenf; J. Huisman; J. W. O. van den Berg

    2010-01-01

    In three experiments (Exp. 1, 2, and 3) with young pigs (BW 10 to 26 kg), the effects of dietary inclusion of hulls of faba beans ( Vicia faba L. (200 g\\/kg) with a low (<.l% catechin equivalents; LT) or high tannin content (3.3% catechin equiva- lents; HT) on the apparent ileal (Exp. 1 and 2) and fecal (Exp. 3)

  19. Nitroglycerin relaxes coronary artery of the pig with no change in glutathione content or glutathione S-transferase activity.

    PubMed Central

    Sakanashi, M.; Matsuzaki, T.; Aniya, Y.

    1991-01-01

    1. The role of glutathione content and glutathione S-transferase activity in vascular relaxant responses to nitroglycerin was evaluated in potassium (30 mM)-contracted coronary artery strips of the pig by measuring changes in tension, glutathione content and glutathione S-transferase activity. 2. Prior exposure of coronary artery strips to nitroglycerin (10(-5)M or 10(-4)M for 20 min) resulted in tachyphylaxis to subsequent relaxation to nitroglycerin (10(-8)-10(-5)M). 3. The glutathione content and glutathione S-transferase activity of the arterial strips rendered tachyphylactic by prior exposure to nitroglycerin (10(-5)M for 20 min or 10(-3)M for 120 min) were not significantly different from those of control strips. 4. Treatment with diethyl maleate (10(-4)M or 10(-3)M for 60 min) markedly depleted arterial glutathione content in a concentration-dependent manner with no change in glutathione S-transferase activity. 5. The relaxant response of coronary artery strips to nitroglycerin (10(-8)-10(-5)M) was completely unaffected following treatment with diethyl maleate (10(-4)M or 10(-3)M for 60 min). 6. The results suggest that vascular glutathione content does not play an important role in vascular relaxation or tolerance development to nitroglycerin, at least in pig isolated coronary artery. PMID:1912979

  20. Regulation of Signal Transduction by Glutathione Transferases

    PubMed Central

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

    2012-01-01

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

  1. Diallyl disulphide depletes glutathione in Candida albicans

    PubMed Central

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

    2008-01-01

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

  2. Interactions of glutathione transferases with 4-hydroxynonenal

    PubMed Central

    Balogh, Larissa M.; Atkins, William M.

    2015-01-01

    Electrophilic products of lipid peroxidation are important contributors to the progression of several pathological states. The prototypical ?,?–unsaturated aldehyde, 4-hydroxynonenal (HNE), triggers cellular events associated with oxidative stress, which can be curtailed by the glutathione-dependent elimination of HNE. The glutathione transferases (GSTs) are a major determinate of the intracellular concentration of HNE and can influence susceptibility to toxic effects, particularly when HNE and GST levels are altered in disease states. In this article, we provide a brief summary of the cellular effects of HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTs. Some of the key determining characteristics that impart high alkenal activity reside in the unique C-terminal interactions of the GSTA4-4 enzyme. Studies encompassing both kinetic and structural analyses of related isoforms will be highlighted, with additional attention to stereochemical aspects that demonstrate the capacity of GSTA4-4 to detoxify both enantiomers of the biologically relevant racemic mixture while generating a select set of diastereomeric products with subsequent implications. A summary of the literature that examines the interplay between GSTs and HNE in model systems relevant to oxidative stress will also be discussed to demonstrate the magnitude of importance of GSTs in the overall detoxification scheme. PMID:21401344

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

    PubMed Central

    2014-01-01

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

  4. Substitution Urethroplasty for Anterior Urethral Strictures: Buccal versus Lingual Mucosal Graft

    Microsoft Academic Search

    Abhay Kumar; Suren K. Das; Sameer Trivedi; Udai S. Dwivedi; Pratap B. Singh

    2010-01-01

    Aim: To compare the results of substitution urethroplasty and donor site morbidity between buccal mucosal graft (BMG) and lingual mucosal graft (LMG). Patients and Methods: Patients who underwent single-stage dorsal onlay free oral mucosal graft substitution urethroplasty by Barbagli’s technique between January 2004 and August 2008 were included in this study. Patients who underwent buccal (cheek, lip) mucosal graft urethroplasty

  5. Type 1 Immunity Provides Optimal Protection against Both Mucosal and Systemic Trypanosoma cruzi Challenges

    Microsoft Academic Search

    D. F. Hoft; C. S. Eickhoff

    2002-01-01

    Chagas' disease results from infection with Trypanosoma cruzi, a protozoan parasite that establishes systemic intracellular infection after mucosal invasion. We hypothesized that ideal vaccines for mucosally invasive, intracellular pathogens like T. cruzi should induce mucosal type 2 immunity for optimal induction of protective secretory immunoglobulin A (IgA) and systemic type 1 immunity protective against intracellular replication. However, differential mucosal and

  6. The Role of Intestinal Microbiota in the Development and Severity of Chemotherapy-Induced Mucositis

    Microsoft Academic Search

    Michel J. van Vliet; Hermie J. M. Harmsen; Wim J. E. Tissing

    2010-01-01

    Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of radiotherapy and chemotherapy treatment. Clinically, mucositis is associated with pain, bacteremia, and malnutrition. Furthermore, mucositis is a frequent reason to postpone chemotherapy treatment, ultimately leading towards a higher mortality in cancer patients. According to the model introduced by Sonis, both inflammation and apoptosis

  7. The efficacy of sucralfate suspension in the prevention of oral mucositis due to radiation therapy

    Microsoft Academic Search

    Joel B. Epstein; Frances L. W. Wong

    1994-01-01

    The purpose of this study was to assess the value of sucralfate suspension in prevention of oral mucositis and for reduction of oral pain in patients who develop mucositis during radiation therapy. The study was a double-blind, placebo-controlled, randomized prospective trial of a sucralfate suspension in the prevention and management of oral mucositis during radiation therapy. Oral mucositis was assessed

  8. Randomized prospective trial comparing ileal pouch-anal anastomosis performed by excising the anal mucosa to ileal pouch-anal anastomosis performed by preserving the anal mucosa.

    PubMed Central

    Reilly, W T; Pemberton, J H; Wolff, B G; Nivatvongs, S; Devine, R M; Litchy, W J; McIntyre, P B

    1997-01-01

    OBJECTIVE: The purpose of the study is to compare the results of ileal pouch-anal anastomosis (IPAA) in patients in whom the anal mucosa is excised by handsewn techniques to those in whom the mucosa is preserved using stapling techniques. SUMMARY BACKGROUND DATA: Ileal pouch-anal anastomosis is the operation of choice for patients with chronic ulcerative colitis requiring proctocolectomy. Controversy exists over whether preserving the transitional mucosa of the anal canal improves outcomes. METHODS: Forty-one patients (23 men, 18 women) were randomized to either endorectal mucosectomy and handsewn IPAA or to double-stapled IPAA, which spared the anal transition zone. All patients were diverted for 2 to 3 months. Nine patients were excluded. Preoperative functional status was assessed by questionnaire and anal manometry. Twenty-four patients underwent more extensive physiologic evaluation, including scintigraphic anopouch angle studies and pudendel never terminal motor latency a mean of 6 months after surgery. Quality of life similarly was estimated before surgery and after surgery. Univariate analysis using Wilcoxon test was used to assess differences between groups. RESULTS: The two groups were identical demographically. Overall outcomes in both groups were good. Thirty-three percent of patients who underwent the handsewn technique and 35% of patients who underwent the double-stapled technique experienced a postoperative complication. Resting anal canal pressures were higher in the patients who underwent the stapled technique, but other physiologic parameters were similar between groups. Night-time fecal incontinence occurred less frequently in the stapled group but not significantly. The number of stools per 24 hours decreased from preoperative values in both groups. After IPAA, quality of life improved promptly in both groups. CONCLUSIONS: Stapled IPAA, which preserves the mucosa of the anal transition zone, confers no apparent early advantage in terms of decreased stool frequency or fewer episodes of fecal incontinence compared to handsewn IPAA, which excises the mucosa. Higher resting pressures in the stapled group coupled with a trend toward less night-time incontinence, however, may portend better function in the stapled group over time. Both operations are safe and result in rapid and profound improvement in quality of life. PMID:9230807

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

    E-print Network

    Paris-Sud XI, Université de

    Effect of vitamin D or calcium deficiency on duodenal, jejunal and ileal calcium-binding protein Josas. Summary. In vitamin D-deficient pigs the amount of intestinal calcium-binding protein (CaBP. In chicks and rats, 25-hydroxycholecalciferol (25-OHD,) is the major circulating metabolite of vitamin D3

  10. 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...

  11. Quality of life after proctocolectomy. A comparison of Brooke ileostomy, Kock pouch, and ileal pouch-anal anastomosis.

    PubMed

    Köhler, L W; Pemberton, J H; Zinsmeister, A R; Kelly, K A

    1991-09-01

    Recent work has shown that patients undergoing proctocolectomy and ileal pouch-anal anastomosis experience a better quality of life than those undergoing proctocolectomy and Brooke ileostomy. To assess whether the improvement with the pouch is due to the absence of a stoma or the preservation of fecal continence, functional and performance activities were assessed in 406 patients with Brooke ileostomies (stoma present, incontinent), 313 with Kock pouches (stoma present, continent), and 298 with ileal pouch-anal anastomoses (stoma absent, continent). All patients underwent proctocolectomy for ulcerative colitis or familial adenomatous polyposis. After adjusting for age, sex, diagnosis, attitude towards the operation, dietary satisfaction, and ability to work, the likelihood of an impact on performance was estimated for the three types of operation using logistic regression analysis. Patients with ileal pouch-anal anastomoses had fewer restrictions in sports and sexual activities than those with Kock pouches (P less than 0.05), whereas those with Kock pouches in turn had fewer restrictions in these activities but more restrictions in travel than those with Brooke ileostomies (P less than 0.05). In contrast, performance in the categories of social life, recreation, work, and family was similar between groups. It is concluded that both the presence of a stoma and fecal incontinence impair the quality of life after proctocolectomy. Ileal pouch-anal anastomosis, which avoids both stoma and incontinence, offers the best quality of life between the three operations studied. PMID:1650316

  12. Evaluation of two external markers for measurement of ileal and total tract digestibility of pigs fed human-type diets.

    PubMed

    Lærke, H N; Kasprzak, M M; Bach Knudsen, K E

    2012-12-01

    External markers for determination of nutrient digestibility have often been evaluated in conventional dry feeds but less often in conventional feeds such as human-type diets used in animal model studies. In the present study, 5 ileal-cannulated pigs were fed 5 types of soft bread-based diets supplemented with Cr(2)O(3) and AIA as digestibility markers for 1 wk in a Latin square design. Ileal contents were collected twice for 5 h and a fecal grab sample was obtained once per week. Ileal and total tract digestibility of OM and nonstarch polysaccharides (NSP) based on the 2 markers were compared by linear regression. Across dietary treatments and site of collection, high correlation existed between digestibility values obtained with Cr(2)O(3) and AIA, resulting in a R(2) > 0.77 (P < 0.001) and a linear relation close to unity. For ileal samples, the correlation was poor, particularly for NSP, which had R(2) = 0.09 (P = 0.14) whereas OM had an R(2) = 0.52 (P <0.001). On the other hand, fecal grab samples led to R(2) > 0.92 (P < 0.001) for both OM and NSP. However, AIA gave higher values than Cr(2)O(3), particularly in samples with lower digestibility. The discrepancy is presumably caused by analytical difficulties due to a high fecal ash contents or interference with other components in the human-type diets. PMID:23365387

  13. Laboratory Tests for Patients With Ileal Pouch–Anal Anastomosis: Clinical Utility in Predicting, Diagnosing, and Monitoring Pouch Disorders

    Microsoft Academic Search

    Udayakumar Navaneethan; Bo Shen

    2009-01-01

    Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the surgical treatment of choice for patients with medically refractory ulcerative colitis (UC) or UC-associated dysplasia, and for the majority of patients with familial adenomatous polyposis. Pouchitis and other complications of IPAA are common. There are scant data on laboratory markers for the evaluation and diagnosis of pouch disorders. The presence of

  14. 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...

  15. Glutathione Synthesis and Turnover in the Human Erythrocyte

    PubMed Central

    Raftos, Julia E.; Whillier, Stephney; Kuchel, Philip W.

    2010-01-01

    The erythrocyte is exposed to reactive oxygen species in the circulation and also to those produced by autoxidation of hemoglobin. Consequently, erythrocytes depend on protection by the antioxidant glutathione. Mathematical models based on realistic kinetic data have provided valuable insights into the regulation of biochemical pathways within the erythrocyte but none have satisfactorily accounted for glutathione metabolism. In the current model, rate equations were derived for the enzyme-catalyzed reactions, and for each equation the nonlinear algebraic relationship between the steady-state kinetic parameters and the unitary rate constants was derived. The model also includes the transport processes that supply the amino acid constituents of glutathione and the export of oxidized glutathione. Values of the kinetic parameters for the individual reactions were measured predominately using isolated enzymes under conditions that differed from the intracellular environment. By comparing the experimental and simulated results, the values of the enzyme-kinetic parameters of the model were refined to yield conformity between model simulations and experimental data. Model output accurately represented the steady-state concentrations of metabolites in erythrocytes suspended in plasma and the changing glutathione concentrations in whole and hemolyzed erythrocytes under specific experimental conditions. Analysis indicated that feedback inhibition of ?-glutamate-cysteine ligase by glutathione had a limited effect on steady-state glutathione concentrations and was not sufficiently potent to return glutathione concentrations to normal levels in erythrocytes exposed to sustained increases in oxidative load. PMID:20498365

  16. Hibernation induces glutathione redox imbalance in ground squirrel intestine

    Microsoft Academic Search

    H. V. Carey; C. A. Rhoads; T. Y. Aw

    2003-01-01

    Glutathione (GSH) is the major thiol-disulfide redox buffer in cells and is a critical component of antioxidant defense. Here we examined GSH redox balance in the intestinal mucosa during the annual cycle of 13-lined ground squirrels ( Spermophilus tridecemlineatus). The ratio of reduced GSH to its oxidized form (glutathione disulfide, GSSG), which is an index of oxidative stress, was five-fold

  17. Glutathione redox system in ? -thalassemia/Hb E patients.

    PubMed

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

    2013-01-01

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

  18. EFFECT OF X-RAY RADIATION ON GLUTATHIONE METABOLISM

    Microsoft Academic Search

    1960-01-01

    Glutathione in the liver, muscles, and blcod of rabbits showed a ; noticeable decrease. A marked decrease of the liver glutathione was seen when a ; single dose of 4000 r was applied to the liver or 1000 r to the whole body. The ; same effect was seen in 6000 r of fractioned irradiation to the liver, or 2000

  19. Characterization of glutathione S-transferases in juvenile white sturgeon

    Microsoft Academic Search

    Rachel T. Donham; Dexter Morin; William T. Jewell; Stephanie A. Burns; Alyson E. Mitchell; M. W. Lamé; H. J. Segall; Ronald S. Tjeerdema

    2005-01-01

    Glutathione S-transferases (GSTs) are a family of detoxification enzymes that catalyze the conjugation of glutathione (GSH) to electrophiles, thus preventing toxicity. This study characterized the cytosolic GST classes of juvenile white sturgeon (Acipenser transmontanus) liver, using two methods of isolation. The first, which employed affinity chromatography, electrophoresis and immunoblotting against a polyclonal striped bass GST antibody, yielded two cytosolic GSTs.

  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 of MSE could be due to its predominant effect on mucosal glycoprotein, cell proliferation, free radicals and antioxidant systems. PMID:16629371

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

    PubMed Central

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

    2011-01-01

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

  2. High-resolution genomic profiling reveals gain of chromosome 14 as a predictor of poor outcome in ileal carcinoids.

    PubMed

    Andersson, Ellinor; Swärd, Christina; Stenman, Göran; Ahlman, Håkan; Nilsson, Ola

    2009-09-01

    Ileal carcinoids are malignant neuroendocrine tumours of the small intestine. The aim of this study was to obtain a high-resolution genomic profile of ileal carcinoids in order to define genetic changes important for tumour initiation, progression and survival. Forty-three patients with ileal carcinoids were investigated by high-resolution array-based comparative genomic hybridization. The average number of copy number alterations (CNAs) per tumour was 7.1 (range 1-22), with losses being more common than gains (ratio 1.4). The most frequent CNA was loss of chromosome 18 (74%). Other frequent CNAs were gain of chromosome 4, 5, 14 and 20, and loss of 11q22.1-q22.2, 11q22.3-q23.1 and 11q23.3, and loss of 16q12.2-q22.1 and 16q23.2-qter. Two distinct patterns of CNAs were found; the majority of tumours was characterized by loss of chromosome 18 while a subgroup of tumours had intact chromosome 18, but gain of chromosome 14. Survival analysis, using a series of Poisson regressions including recurrent CNAs, demonstrated that gain of chromosome 14 was a strong predictor of poor survival. In conclusion, high-resolution profiling demonstrated two separate patterns of CNAs in ileal carcinoids. The majority of tumours showed loss of chromosome 18, which most likely represents a primary event in the development and pathogenesis of tumours. A different genetic pathway is operative in a subgroup of tumours; this is characterized by gain of chromosome 14 and is strongly associated with poor prognosis. Predictive fluorescence in situ hybridization analysis of chromosome 14 status in patients with ileal carcinoids is suggested. PMID:19458023

  3. Anaerobic bacteremia in a neutropenic patient with oral mucositis.

    PubMed

    Vidal, A M; Sarria, J C; Kimbrough, R C; Keung, Y K

    2000-03-01

    An increasing number of anaerobic bloodstream infections in neutropenic cancer patients have been reported in the last decade. The type of anaerobes isolated from most of these patients suggests an oral source of infection. We describe a case of anaerobic bacteremia in a neutropenic patient with oral mucositis that highlights the importance of considering these organisms when selecting empiric prophylactic or therapeutic antimicrobial regimens, especially in the setting of periodontal disease or oral mucositis. PMID:10746831

  4. Polymeric penetration enhancers promote humoral immune responses to mucosal vaccines.

    PubMed

    Klein, Katja; Mann, Jamie F S; Rogers, Paul; Shattock, Robin J

    2014-06-10

    Protective mucosal immune responses are thought best induced by trans-mucosal vaccination, providing greater potential to generate potent local immune responses than conventional parenteral vaccination. However, poor trans-mucosal permeability of large macromolecular antigens limits bioavailability to local inductive immune cells. This study explores the utility of polymeric penetration enhancers to promote trans-mucosal bioavailability of insulin, as a biomarker of mucosal absorption, and two vaccine candidates: recombinant HIV-1 envelope glycoprotein (CN54gp140) and tetanus toxoid (TT). Responses to vaccinating antigens were assessed by measurement of serum and the vaginal humoral responses. Polyethyleneimine (PEI), Dimethyl-?-cyclodextrin (DM-?-CD) and Chitosan enhanced the bioavailability of insulin following intranasal (IN), sublingual (SL), intravaginal (I.Vag) and intrarectal (IR) administration. The same penetration enhancers also increased antigen-specific IgG and IgA antibody responses to the model vaccine antigens in serum and vaginal secretions following IN and SL application. Co-delivery of both antigens with PEI or Chitosan showed the highest increase in systemic IgG and IgA responses following IN or SL administration. However the highest IgA titres in vaginal secretions were achieved after IN immunisations with PEI and Chitosan. None of the penetration enhancers were able to increase antibody responses to gp140 after I.Vag immunisations, while in contrast PEI and Chitosan were able to induce TT-specific systemic IgG levels following I.Vag administration. In summary, we present supporting data that suggest appropriate co-formulation of vaccine antigens with excipients known to influence mucosal barrier functions can increase the bioavailability of mucosally applied antigens promoting the induction of mucosal and systemic antibody responses. PMID:24657807

  5. Malignant mucosal melanoma of the head and neck — a review

    Microsoft Academic Search

    Erzsébet Lengyel; Katalin Gilde; Éva Remenár; Olga Ésik

    2003-01-01

    Mucosal melanomas comprise about 1% of all malignant melanomas and exhibit far more aggressive behaviour than that of skin\\u000a melanomas: they are more inclined to metastatize into regional and distant sites or recur locally, regionally or in distant\\u000a locations, resulting in a high rate of cause-specific death. Mucosal melanomas in the head and neck region account for half\\u000a of all

  6. Use of Nonhuman Primate Models to Develop Mucosal AIDS Vaccines

    Microsoft Academic Search

    Meritxell Genescà; Christopher J. Miller

    2010-01-01

    The HIV vaccines tested in the halted Step efficacy trial and the modestly successful phase 3 RV144 trial were designed to\\u000a elicit strong systemic immune responses; therefore, strategies to direct immune responses into mucosal sites should be tested\\u000a in an effort to improve AIDS vaccine efficacy. However, as increased CD4+ T-cell activation and recruitment to mucosal sites have the potential

  7. Evidence for accelerated rates of glutathione utilization and glutathione depletion in adolescents with poorly controlled type 1 diabetes.

    PubMed

    Darmaun, Dominique; Smith, Shiela D; Sweeten, Shawn; Sager, Brenda K; Welch, Susan; Mauras, Nelly

    2005-01-01

    Depletion of glutathione, an important antioxidant present in red cells, has been reported in type 1 diabetes, but the mechanism of this depletion has not been fully characterized. Glutathione depletion can occur through decreased synthesis, increased utilization, or a combination of both. To address this issue, 5-h infusions of l-[3,3-(2)H(2)]cysteine were performed in 16 diabetic adolescents divided into a well-controlled and a poorly controlled group and in eight healthy nondiabetic teenagers as control subjects (HbA(1c) 6.3 +/- 0.2, 10.5 +/- 0.6, and 4.8 +/- 0.1%, respectively). Glutathione fractional synthesis rate was determined from (2)H(2)-cysteine incorporation into blood glutathione. We observed that 1) erythrocyte cysteine concentration was 41% lower in poorly controlled patients compared with well-controlled patients (P = 0.009); 2) erythrocyte glutathione concentration was approximately 29% and approximately 36% lower in well-controlled and poorly controlled patients compared with healthy volunteers; and 3) the fractional synthesis rate of glutathione, although similar in well-controlled and healthy subjects (83 +/- 14 vs. 82 +/- 11% per day), was substantially higher in the poorly controlled group (141 +/- 23% per day, P = 0.038). These findings suggest that in diabetic adolescents, poor control is associated with a significant depletion of blood glutathione and cysteine, due to increased rates of glutathione utilization. This weakened antioxidant defense may play a role in the pathogenesis of diabetes complications. PMID:15616028

  8. Efficient nitrosation of glutathione by nitric oxide?

    PubMed Central

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

    2013-01-01

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

  9. Nomenclature for mammalian soluble glutathione transferases.

    PubMed

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

    2005-01-01

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

  10. Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats

    PubMed Central

    Birdane, Fatih Mehmet; Cemek, Mustafa; Birdane, Yavuz Osman; Gülçin, ?lhami; Büyükokuro?lu, Mehmet Emin

    2007-01-01

    AIM: To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vulgare (FVE) on ethanol-induced gastric lesions in rats. METHODS: FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated; whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid, retinol and ?-carotene levels were measured in all the groups. RESULTS: It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 ± 2.81 vs 13.15 ± 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid, retinol and ?-carotene levels. CONCLUSION: FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity. PMID:17278229

  11. Apple polyphenol extracts protect against aspirin-induced gastric mucosal damage in rats.

    PubMed

    Paturi, Gunaranjan; Butts, Christine A; Bentley-Hewitt, Kerry L; McGhie, Tony K; Saleh, Zaid S; McLeod, Andrew

    2014-12-01

    The protective role of two apple polyphenol extracts, Douglas-FB (FB) and Douglas-EF (EF), on gastric mucosal damage following aspirin ingestion was investigated in healthy rats. Polyphenol content of the apple extracts varied, with the EF extract having 20%?w/w polyphenols and a high proportion of flavanols as epicatechin and procyanidin, whereas the FB extract comprised 12%?w/w polyphenols, which were mostly flavonols as quercetin glycosides. Male Sprague-Dawley rats were allocated to control, FB and EF groups and fed the experimental diet during the 10-day trial. Control treatment rats received 1?mL of deionised water, whereas apple polyphenol treatment group rats, FB and EF received a concentration of 10(-2) ?m polyphenols in 1?mL deionised water daily via oral gavage. At the end of 10-day feeding period, rats were fasted overnight, and the following morning, aspirin (200?mg/kg) was given by oral gavage. Four hours after aspirin administration, the animals were euthanised, and samples taken for analysis. Both apple polyphenol extracts significantly reduced the ulcer area, ulcer lesion index and gastric injury score. The glutathione in gastric mucosa was increased significantly in rats given FB apple extract. Despite their different polyphenol compositions, FB and EF apple extracts assisted in protecting the gastric mucosa following acute aspirin administration in rats. PMID:25069887

  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. A Mucosal Adjuvant for the Inactivated Poliovirus Vaccine

    PubMed Central

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

    2014-01-01

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

  14. Definition and evaluation of mucosal healing in clinical practice.

    PubMed

    Mazzuoli, Silvia; Guglielmi, Francesco W; Antonelli, Elisabetta; Salemme, Marianna; Bassotti, Gabrio; Villanacci, Vincenzo

    2013-12-01

    Since the introduction of biological therapy, endoscopic and histological remission, i.e. mucosal healing, has become an important therapeutic goal in Crohn's Disease and Ulcerative Colitis. Mucosal healing is associated with lower rates of hospitalization and surgery, although its role in preventing progression and changing the natural history of the disease has not been clearly demonstrated. A precise definition of mucosal healing has not yet been established, although the concept used in clinical trials is the "complete absence of all inflammatory and ulcerative lesions in all segments of gut" at endoscopy. This definition does not include mucosal improvement and does not distinguish among grades of mucosal healing. In both Crohn's Disease and Ulcerative Colitis trials, several qualitative and quantitative numeric endoscopic indices have been proposed to measure and distinguish endoscopic changes. In addition, the microscopic features associated with inflammatory bowel diseases are considerably modified by the course of the disease and the treatments adopted. However, it is not yet clear whether microscopic healing should be a primary endpoint in clinical trials. In this paper we discuss endoscopic and histological findings and the limitations of the endoscopic and histological indices as a basis for a standardised diagnosis of mucosal healing. PMID:23932331

  15. Glutathione-S-Transferase Activity and Metabolism of Glutathione Conjugates by Rhizosphere Bacteria

    Microsoft Academic Search

    ROBERT M. ZABLOTOWICZ; ROBERT E. HOAGLAND; MARTIN A. LOCKE

    1995-01-01

    Glutathione-S-transferase (GST) activity was determined in 36 species of rhizosphere bacteria with the substrate 1-chloro-2,4-dinitrobenzene (CDNB) and in 18 strains with the herbicide alachlor. Highest levels of CDNB-GST activity (60 to 222 nmol z h21 z mg21) were found in gram-negative bacteria:Enterobacter cloacae, Citrobacter diversus, Klebsiella planticola, Pseudomonas cepacia, Pseudomonas fluorescens, Pseudomonas putida, and Xanthomonas campestris. There was very low

  16. Glutathione-S-Transferase Activity and Metabolism of Glutathione Conjugates by Rhizosphere Bacteria

    PubMed Central

    Zablotowicz, R. M.; Hoagland, R. E.; Locke, M. A.; Hickey, W. J.

    1995-01-01

    Glutathione-S-transferase (GST) activity was determined in 36 species of rhizosphere bacteria with the substrate 1-chloro-2,4-dinitrobenzene (CDNB) and in 18 strains with the herbicide alachlor. Highest levels of CDNB-GST activity (60 to 222 nmol (middot) h(sup-1) (middot) mg(sup-1)) were found in gram-negative bacteria: Enterobacter cloacae, Citrobacter diversus, Klebsiella planticola, Pseudomonas cepacia, Pseudomonas fluorescens, Pseudomonas putida, and Xanthomonas campestris. There was very low CDNB-GST activity in the gram-positive strains. Rapid metabolism of CDNB-glutathione conjugates, attributable to high levels of (gamma)-glutamyltranspeptidase, also occurred in the gram-negative bacteria, especially pseudomonads. Alachlor-GST activity detected in cell extracts and whole-cell suspensions of some strains of the families Enterobacteriaceae and Pseudomonaceae was 50- to 100-fold lower than CDNB-GST activity (0.5 to 2.5 nmol (middot) h(sup-1) (middot) mg(sup-1)) and was, for the most part, constitutive. The glutathione-alachlor conjugate was rarely detected. Cysteineglycine and/or cysteine conjugates were the major products of alachlor-GST metabolism. Whole-cell suspensions of certain Pseudomonas spp. dechlorinated from 20 to 75% of 100 (mu)M alachlor in 24 h. Results indicate that rhizosphere bacteria, especially fluorescent pseudomonads, may play an important role in the degradation of xenobiotics such as alachlor via GST-mediated reactions. PMID:16534956

  17. Mucosal effects of tenofovir 1% gel.

    PubMed

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

    2015-01-01

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

  18. Mucosal Inflammatory Response to Salmonella typhimurium Infection

    PubMed Central

    Patel, Samir; McCormick, Beth A.

    2014-01-01

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

  19. 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. PMID:17991162

  20. Clotrimazole nanoparticle gel for mucosal administration.

    PubMed

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

    2013-01-01

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

  1. Sino-nasal mucosal malignant melanoma.

    PubMed

    Karim, Muneeb Uddin; Khan, Khursheed; Ali, Nasir; Ikram, Mubasher

    2015-01-01

    A 49-year-old man with a history of left nasal discharge and nasal cavity blockage for 5?months was diagnosed with sino-nasal mucosal malignant melanoma on nasal biopsy. On CT scan, the tumour involved the nasal cavity, left maxillary sinus, ethmoid sinus and medial left orbit. The tumour was grossly excised and adjuvant radiation therapy was offered. The patient was planned for an Intensity Modulated Radiotherapy technique to keep tolerance doses of organs at risk within normal limits and at same time deliver the intended dose of radiation to the tumour site, using 66?Gy in 33 fractions. Owing to the anatomical complexity of the sino-nasal region, precision radiotherapy (RT) is mandatory to optimally irradiate the tumour area while sparing critical surrounding normal structures from late toxicity of RT. Established dose constraints for at-risk organs can only be accomplished through this novel technique of RT. However, despite advances in techniques, current treatment modalities have not significantly made an impact on survival of these patients. PMID:25926579

  2. Laparoscopy-assisted ileal pouch-anal anastomosis: surgical outcomes after 10 cases.

    PubMed

    Araujo, Sergio Eduardo Alonso; Nahas, Sergio Carlos; Seid, Victor Edmond; Marchini, Giovanni Scala; Torricelli, Fabio César Miranda

    2005-12-01

    We analyzed outcomes of laparoscopy-assisted ileal pouch-anal anastomosis (LAIPA) from 10 patients (7 with ulcerative colitis and 3 with familial adenomatous polyposis) operated on between January 1998 and March 2004. Median operating time was 246 minutes. There were no intraoperative complications. There were no conversions. Postoperative complications occurred in 3 (30%) patients: 2 cases of wound infection and 1 case of a foreign body retrieved during pouch endoscopy. There was a 30% reoperation rate due to unsuspected duodenal perforation, a persistent postoperative pain, and 1 case of intestinal obstruction after ileostomy closure. There were no deaths. Median time to resumption of diet was 24 hours. Median hospital stay was 7 days. All ileostomies were closed 6 to 8 weeks after LAIPA. LAIPA is feasible and safe and should be selectively offered to nonobese patients. PMID:16340561

  3. False positive GI bleed on Tc-99m RBC scintigraphy due to ileal varices.

    PubMed

    Chen, Paul Ning-Chuan; Brown, Richard Kevin

    2012-02-01

    Tc-99m labeled RBC scintigraphy is commonly employed in the evaluation of acute gastrointestinal bleeding. On Tc-99m RBC studies gastrointestinal bleeding is seen as an initial focus of increased radiotracer activity that on subsequent images increases in intensity and changes position in a pattern that conforms to segments of bowel. We report a case of a patient with multiple episodes of hematochezia that presented with lower gastrointestinal hemorrhage. A Tc-99m labeled RBC scan was performed and the findings suggested a GI bleed. However, subsequent angiography revealed prominent ileal varices simulating an acute bleed. Although most varices fill promptly and should not be misinterpreted as a focus of hemorrhage, slow filling varices can simulate an acute bleed and lead to a false positive interpretation. PMID:22690283

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

    PubMed Central

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

    2014-01-01

    Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the current gold standard in the surgical treatment of ulcerative colitis (UC) refractory to medical management. A procedure of significant magnitude carries its own risks including anastomotic failure, pelvic sepsis and a low rate of neoplastic degeneration overtime. Recent studies have shown that total colectomy with ileorectal anastomosis (IRA) has been associated with good long-term functional results in a selected group of UC patients amenable to undergo a strict surveillance for the relatively high risk of cancer in the rectum. This manuscript will review and compare the most recent literature on IRA and IPAA as it pertains to postoperative morbidity and mortality, failure rates, functional outcomes and cancer risk. PMID:25309058

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

    PubMed

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

    2004-11-01

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

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

    PubMed Central

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

    2013-01-01

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

  7. Complications after ileal pouch-anal anastomosis in Korean patients with ulcerative colitis

    PubMed Central

    Ryoo, Seung-Bum; Oh, Heung-Kwon; Han, Eon Chul; Ha, Heon-Kyun; Moon, Sang Hui; Choe, Eun Kyung; Park, Kyu Joo

    2014-01-01

    AIM: To investigate the outcomes of treatments for complications after ileal pouch-anal anastomosis (IPAA) in Korean patients with ulcerative colitis. METHODS: Between March 1998 and February 2013, 72 patients (28 male and 44 female, median age 43.0 years ± 14.0 years) underwent total proctocolectomy with IPAA. The study cohort was registered prospectively and analyzed retrospectively. Patient characteristics, medical management histories, operative findings, pathology reports and postoperative clinical courses, including early postoperative and late complications and their treatments, were reviewed from a medical record system. All of the ileal pouches were J-pouch and were performed with either the double-stapling technique (n = 69) or a hand-sewn (n = 3) technique. RESULTS: Thirty-one (43.1%) patients had early complications, with 12 (16.7%) patients with complications related to the pouch. Pouch bleeding, pelvic abscesses and anastomosis ruptures were managed conservatively. Patients with pelvic abscesses were treated with surgical drainage. Twenty-seven (38.0%) patients had late complications during the follow-up period (82.5 ± 50.8 mo), with 21 (29.6%) patients with complications related to the pouch. Treatment for pouchitis included antibiotics or anti-inflammatory drugs. Pouch-vaginal fistulas, perianal abscesses or fistulas and anastomosis strictures were treated surgically. Pouch failure developed in two patients (2.8%). Analyses showed that an emergency operation was a significant risk factor for early pouch-related complications compared to elective procedures (55.6% vs 11.1%, P < 0.05). Pouchitis was related to early (35.3%) and the other late pouch-related complications (41.2%) (P < 0.05). The complications did not have an effect on pouch failure nor pouch function. CONCLUSION: The complications following IPAA can be treated successfully. Favorable long-term outcomes were achieved with a lower pouch failure rate than reported in Western patients. PMID:24966620

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

    PubMed

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

    2011-05-11

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

  9. Pharmacological characterization of a 7-benzylidenenaltrexone-preferring opioid receptor in porcine ileal submucosa.

    PubMed

    Townsend, De Wayne; Brown, David R

    2003-10-01

    In the intestine, opioids produce antidiarrhoeal and constipating actions that are mediated by enteric neurones. Through interactions with opioid receptors (ORs) on submucosal neurones, opioids suppress active ion transport evoked by transmural electrical stimulation (TES) in mucosa-submucosa sheets from the porcine ileum. In this study, we examined the pharmacological characteristics of the previously described OR, which is sensitive to the delta1-OR antagonist 7-benzylidenenaltrexone and modulates neurogenic transepithelial ion transport in this tissue preparation. Increases in short-circuit current (Isc, a measure of active anion transport) evoked by TES in ileal mucosa-submucosa sheets were inhibited by opioid agonists possessing high selectivity for either delta- or micro-ORs including [d-Pen2,5]enkephalin (DPDPE), [d-Ala2, Glu4]deltorphin II, and [d-Ala2, N-Me-Phe4, Gly5-ol]enkephalin (DAMGO). As determined by the Schild analysis, the actions of these agonists were competitively inhibited by 7-benzylidenenaltrexone. The nonequilibrium micro-OR antagonist beta-funaltrexamine inhibited the actions of DAMGO only at a high concentration (1 microm) but did not alter DPDPE or deltorphin II action. At concentrations up to 10 microm, the nonequilibrium delta-OR antagonist naltrindole 5'-isothiocyanate did not alter the actions of delta- or micro-OR agonists. Radioligand binding analyses of neuronal homogenates from the ileal submucosa revealed that the nonselective OR ligand [3H]diprenorphine bound to two populations of specific binding sites. One of these sites possessed binding characteristics similar to the delta-OR. In summary, neurogenic ion transport in the porcine intestine is modulated by an OR which shares pharmacological characteristics of both micro- and delta-ORs and may represent a novel receptor entity. PMID:14534152

  10. Intraductal papillary mucinous neoplasm of the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer: A case report

    PubMed Central

    Lee, Sang Hwa; Kim, Wook Youn; Hwang, Dae-Yong; Han, Hye Seung

    2015-01-01

    We report a case of intraductal papillary mucinous neoplasm (IPMN) originating from the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer (HNPCC). A 49-year-old woman had a past history of total colectomy and total hysterectomy with bilateral salpingo-oophorectomy due to colonic adenocarcinoma and endometrial adenocarcinoma 11 years ago. Her parents died from colonic adenocarcinoma and her sister died from colonic adenocarcinoma and endometrial adenocarcinoma. The clinician found an ileal mass with necrotic change and the mass increased in size from 1.7 cm to 2.2 cm during the past 2 years on computed tomography. It was surgically resected. Microscopically, the ileal mass showed heterotopic pancreas with IPMN high grade dysplasia. Immunohistochemical staining revealed positive reactivity for MLH1/PMS2 and negative reactivity for MSH2/MSH6. This is the first report of IPMN originating from the ileal heterotopic pancreas in a patient with HNPCC in the English literature.

  11. Glutathione activates virulence gene expression of an intracellular pathogen

    PubMed Central

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

    2015-01-01

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

  12. Glutathione-dependent peroxidative metabolism in the alveolar macrophage

    PubMed Central

    Vogt, Molly T.; Thomas, Catherine; Vassallo, Charles L.; Basford, R. E.; Gee, J. Bernard L.

    1971-01-01

    Phagocytosis by rabbit alveolar macrophages (AM) is accompanied by increases in O2 consumption, glucose oxidation, and H2O2 formation. Two aspects of the interrelations between these metabolic features of phagocytosis have been studied. First, the following evidence indicates that glutathione, glutathione reductase, and peroxidase serve as a cytoplasmic shuttle between H2O2 and NADPH-dependent glucose oxidation: (a) AM contain 5.9 m?moles of reduced glutathione per 106 cells and exhibit glutathione peroxidase and NADPH-specific glutathione reductase activity; (b) oxidized glutathione potentiates NADP stimulation of glucose oxidation; (c) an artificial H2O2-generating system stimulates glucose oxidation; (d) the cell penetrating thiol inhibitor, N-ethylmaleimide diminishes glucose oxidation. This effect largely depends on inhibition of the glutathione system rather than on inhibition of either H2O2 formation or enzymes directly subserving glucose oxidation. Second, three potential H2O2-generating oxidases have been sought. No cyanide-insensitive NADH or NADPH oxidase activity could be detected. D-amino acid oxidase activity was 0.48 ±0.07 U/106 cells with D-alanine as substrate. PMID:4395562

  13. Glutathione imbalance in patients with X-linked adrenoleukodystrophy?

    PubMed Central

    Petrillo, Sara; Piemonte, Fiorella; Pastore, Anna; Tozzi, Giulia; Aiello, Chiara; Pujol, Aurora; Cappa, Marco; Bertini, Enrico

    2013-01-01

    Background X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder of X-linked inheritance caused by a mutation in the ABCD1 gene which determines an accumulation of long-chain fatty acids in plasma and tissues. Recent evidence shows that oxidative stress may be a hallmark in the pathogenesis of X-ALD and glutathione plays an important role in the defense against free radicals. In this study we have analyzed glutathione homeostasis in lymphocytes of 14 patients with X-ALD and evaluated the balance between oxidized and reduced forms of glutathione, in order to define the role of this crucial redox marker in this condition. Methods Lymphocytes, plasma and erythrocytes were obtained from the whole blood of 14 subjects with X-ALD and in 30 healthy subjects. Total, reduced and protein-bound glutathione levels were measured in lymphocytes by HPLC analysis. Erythrocyte free glutathione and antioxidant enzyme activities, plasma thiols and carbonyl content were determined by spectrophotometric assays. Results A significant decrease of total and reduced glutathione was found in lymphocytes of patients, associated to high levels of all oxidized glutathione forms. A decline of free glutathione was particularly significant in erythrocytes. The increased oxidative stress in X-ALD was additionally confirmed by the decrease of plasma thiols and the high level of carbonyls. Conclusion Our results strongly support a role for oxidative stress in the pathophysiology of X-ALD and strengthen the importance of the balance among glutathione forms as a hallmark and a potential biomarker of the disease. PMID:23768953

  14. Impact of wheat grinding and pelleting in a wheat–rapeseed meal diet on amino acid ileal digestibility and endogenous losses in pigs

    Microsoft Academic Search

    L. Lahaye; P. Ganier; J. N. Thibault; Y. Riou; B. Sève

    2008-01-01

    The purpose of the current experiment was to investigate the impacts of grinding and pelleting procedures applied to wheat in a wheat–rapeseed meal diet on the coefficients of standardized ileal digestibility, i.e., apparent digestibility corrected for basal endogenous losses (CSID), and true ileal digestibility, i.e., apparent digestibility corrected for total endogenous losses (CTID), of nitrogen (N) and amino acids (AA)

  15. Clinicopathological evaluation of anoxic mucosal injury in strangulation ileus

    PubMed Central

    2014-01-01

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

  16. 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

  17. Treatment and prognosis of oral mucosal melanoma.

    PubMed

    Sun, Chuan-Zheng; Chen, Yan-Feng; Jiang, Yu-E; Hu, Ze-Dong; Yang, An-Kui; Song, Ming

    2012-07-01

    To evaluate the treatment and prognosis of oral mucosal melanoma (OMM) and provide basic data for clinical treatment. Retrospective analysis of clinicopathological data on OMM from January 1976 to December 2005. Survival analysis was performed and Kaplan-Meier analysis was used to compare the effects of clinicopathological factors on survival using SPSS 18.0 software. A Cox model was applied for multivariate analysis. The 3-year and 5-year overall survival (OS) rates of 51 cases of OMM were 35.0% and 20.7%, respectively. Lymph node metastatic sites were predominantly at levels Ib-III (29/31, 93.5%). Patients of age ?55 years and size ?4 cm had a lower survival rate than those of aged <55 years and size <4 cm. The 3-year OS and 5-year OS of patients who underwent surgery combined with biotherapy or biochemotherapy (70.1% and 58.4%, respectively) were significantly higher than that of patients who underwent other therapeutic regimens (including surgery, chemotherapy, surgery combined with radiotherapy or surgery combined with chemotherapy) (25.0% and 12.5%, respectively). Multivariate analysis showed that surgery combined with biotherapy or biochemotherapy and neck dissection were effective treatments for OMM. Patients aged ?55 years had a worse prognosis than those aged <55 years. OMM has a poor prognosis, but multimodality treatment including surgery combined with biotherapy may improve the prognosis. In patients aged ?55 years with tumor size ?4 cm, increasing the scope of resection may be effective. Elective levels I-III neck dissection should be considered in TanyNOMO cases. PMID:22349277

  18. Mucosal and systemic candidiasis in congenitally immunodeficient mice.

    PubMed Central

    Cantorna, M T; Balish, E

    1990-01-01

    Colony counts and light microscopy were used to assess the capacity of Candida albicans to colonize, infect the alimentary tract, and cause disseminated disease in athymic (nu/nu), euthymic (nu/+), beige (bg/bg), black (bg/+), beige athymic (bg/bg nu/nu), or beige euthymic (bg/bg nu/+) germfree mice. The alimentary tracts of all six genotypes of germfree mice were quickly colonized after exposure to yeast-phase C. albicans. Only bg/bg nu/nu mice showed obvious morbidity and mortality after mucosal colonization with C. albicans. Histopathology of C. albicans-colonized immunocompetent (nu/+, bg/+) and singly immunodeficient (nu/nu, bg/bg, bg/bg nu/+) mice showed minimal to moderate mucosal infections, whereas doubly immunodeficient (bg/bg nu/nu) mice showed extensive yeast and hyphal infection of the palate, tongue, esophagus, and stomach. A progressive systemic infection in C. albicans-colonized mice occurred only in bg/bg nu/nu mice 12 to 16 weeks after colonization and mucosal infection. Thus, it appears that a combination of defective cell-mediated immunity and phagocytic cell defects (polymorphonuclear leukocytes and/or macrophages) predisposed mice to severe mucosal and systemic candidiasis of endogenous origin. This is the first report of a mouse strain that is not only naturally susceptible to mucosal and systemic candidiasis of endogenous origin but also shows lethality at early (1 to 4 weeks) and late (12 to 16 weeks) times after alimentary tract colonization. Images PMID:2180820

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

    PubMed

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

    2015-08-01

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

  20. Microinjected glutathione reductase crystals as indicators of the redox status in living cells

    Microsoft Academic Search

    Michael A. Keese; Rainer Saffrich; Thomas Dandekar; Katja Becker; R. Heiner Schirmer

    1999-01-01

    The flavoenzyme glutathione reductase catalyses electron transfer reactions between two major intracellular redox buffers, namely the NADPH\\/NADP+ couple and the 2 glutathione\\/glutathione disulfide couple. On this account, microcrystals of the enzyme were tested as redox probes of intracellular compartments. For introducing protein crystals into human fibroblasts, different methods (microinjection, particle bombardment and optical tweezers) were explored and compared. When glutathione

  1. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  2. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  3. 21 CFR 862.1365 - Glutathione test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  4. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  5. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  6. 21 CFR 864.7375 - Glutathione reductase assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

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

    PubMed

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

    2013-09-01

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

  8. 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. PMID:24724477

  9. Radical cystectomy and pelvic lymphadenectomy with ileal conduit urinary diversion and abdominal wall reconstruction: an interesting case of multidisciplinary management

    PubMed Central

    Sofos, Stratos S; Walsh, Ciaran J; Parr, Nigel J; Hancock, Kevin

    2015-01-01

    The ileal conduit for urinary diversion after radical cystectomy is a well-described procedure. Furthermore, parastomal hernias, prolapse, stenosis, and retraction of the stoma have been reported as some of the more common complications of this procedure. The subsequent repair of parastomal hernias with a biological mesh and the potential of the conduit to “tunnel” through it has also been described. In this case report, we present a combined repair of a large incisional hernia with a cystectomy and a pelvic lymphadenectomy for invasive bladder cancer, with the use of a biological mesh for posterior component abdominal wall primary repair as well as for support to the ileal conduit used for urinary diversion. PMID:25653561

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-02-27

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

  12. Surgical Treatment of Morbid Obesity: Midterm Outcomes of the Laparoscopic Ileal Interposition Associated to a Sleeve Gastrectomy in 120 Patients

    Microsoft Academic Search

    Aureo L. DePaula; Alessandro R. Stival; Alfredo Halpern; Sergio Vencio

    2011-01-01

    The aim of this study was to evaluate the mid-term outcomes of the laparoscopic ileal interposition associated to a sleeve\\u000a gastrectomy (LII-SG) for the treatment of morbid obesity. The procedure was performed in 120 patients: 71 women and 49 men\\u000a with mean age of 41.4 years. Mean body mass index (BMI) was 43.4?±?4.2 kg\\/m2. Patients had to meet requirements of the 1991

  13. Antidiarrhoeal activity of loperamide: studies of its influence on ion transport across rabbit ileal mucosa in vitro

    Microsoft Academic Search

    S Hughes; N B Higgs; L A Turnberg

    1982-01-01

    Loperamide is a well-established antidiarrhoeal agent with effects on gastrointestinal motility. We have now shown that the drug influences ion transport. In isolated rabbit ileal mucosa loperamide caused a dose-related fall in potential difference and short-circuit current and reduced the serosa to mucosa flux of chloride. The electrical effects were inhibited by naloxone (10(-6)M) suggesting that they were mediated by

  14. Involvement of HER2\\/ neu and metastasis-related proteins in the development of ileal neuroendocrine tumors

    Microsoft Academic Search

    Cinzia Azzoni; Lorena Bottarelli; Stefano Cecchini; Costanza Lagrasta; Silvia Pizzi; Tiziana D’Adda; Elisa Tamburini; Guido Rindi; Cesare Bordi

    2011-01-01

    HER-2\\/neu overexpression and\\/or gene amplification occurs in several human malignancies, frequently correlates with tumor\\u000a aggressiveness, and provides the basis for treatment with trastuzumab. Among neuroendocrine neoplasms (NEN) of the gastroenteropancreatic\\u000a (GEP) tract, ileal neuroendocrine tumors show peculiar features of malignancy with frequent metastases at the diagnosis. We\\u000a investigated the overexpression and\\/or amplification of HER-2\\/neu and the involvement of the metastasis-related

  15. Dietary supplementation with Chinese herbal powder enhances ileal digestibilities and serum concentrations of amino acids in young pigs

    Microsoft Academic Search

    X. F. Kong; Y. L. Yin; Q. H. He; F. G. Yin; H. J. Liu; T. J. Li; R. L. Huang; M. M. Geng; Z. Ruan; Z. Y. Deng; M. Y. Xie; G. Wu

    2009-01-01

    This study was designed to determine the effect of ultra-fine Chinese herbal powder as a dietary additive on serum concentrations\\u000a and apparent ileal digestibilities (AID) of amino acids (AA) in young pigs. In Experiment 1, 60 Duroc × Landrace × Yorkshire\\u000a piglets weaned at 21 days of age were randomly assigned to one of three treatments, representing supplementation with 0 or\\u000a 2 g\\/kg of the powder,

  16. Total tract and ileal nutrient digestibility of a diet fed as mash or crumbled pellets to two laying hybrids

    Microsoft Academic Search

    Annsofie Wahlström; Klas Elwinger; Sigvard Thomke

    1999-01-01

    Two diets, one fed as mash and the other as crumbled pellets, with the same composition and calculated nutrient content, were studied. Two hybrids were used, Lohmann Selected Leghorn (LSL) and SLU-1329 (a cross bred of Leghorn×Rhode Island Red-line). Chromium oxide was used as a digesta flow marker at the ileal level. Feed consumption was recorded during 5 days and

  17. Use of N?amino acid isotope dilution techniques to determine endogenous amino acids in ileal digesta in growing pigs

    Microsoft Academic Search

    Vince M. Gabert; Nuria Canibe; Henry Jørgensen; Bjørn O. Eggum; Willem C. Sauer

    1997-01-01

    An experiment was carried out to determine the contribution of endogenous amino acids (AA) to total AA, using the N?AA and N?leucine isotope dilution techniques, in ileal digesta from growing pigs. Four barrows, initial body weight (BW) 33.8 ± 1.0 kg, were fitted with a simple T?cannula at the distal ileum and one catheter in each of the external jugular

  18. Gata4 Is Essential for the Maintenance of Jejunal-Ileal Identities in the Adult Mouse Small Intestine

    Microsoft Academic Search

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

    2006-01-01

    Gata4, a member of the zinc finger family of GATA transcription factors, is highly expressed in duodenum and jejunum but is nearly undetectable in distal ileum of adult mice. We show here that the caudal reduction of Gata4 is conserved in humans. To test the hypothesis that the regional expression of Gata4 is critical for the maintenance of jejunal-ileal homeostasis

  19. Ileal, colonic and total tract nutrient digestibility in dogs (Canis familiaris) compared with total tract digestibility in mink (Neovison vison).

    PubMed

    Tjernsbekk, Maria Therese; Tauson, Anne-Helene; Ahlstrøm, Oystein

    2014-01-01

    Mink (Neovison vison) was studied as a model for the determination of ileal crude protein (CP) and amino acid (AA) digestibility in dogs (Canis familiaris). Apparent ileal digestibility (AID) and apparent colonic digestibility (ACD) in dogs and apparent total tract digestibility (ATTD) in dogs and mink were measured for dry matter (DM), main nutrients and AA. Standardised ileal digestibility (SID) of CP and AA in dogs was calculated. Twelve dogs and 12 mink divided into three groups were fed one out of three diets differing in CP digestibility. In dogs, AID of CP was lower (74.4%) than ATTD (83.5%) (p < 0.001). The ATTD of CP in mink (77.8%) did not differ from AID, ACD (78.5%) and SID (79.6%) in dogs. Digestibility of AA followed the same pattern, and, except for Thr and Ser, ATTD in mink was very close to SID in dogs. Also, AID was close to ATTD in mink for several AA. High correlations were found between methods for digestibility of CP and most AA (p < 0.01) and for AA ranking with respect to digestibility level (p < 0.001). In dogs, ether extract digestibility was approximately 96% at all sites, while DM, starch and total carbohydrate digestibility increased from ileal to faecal level (p < 0.01). Mink ATTD of DM and main nutrients was closest to ACD in dogs. It was concluded that mink is a suitable model for the determination of AID and SID of CP and AA in dogs. PMID:24870271

  20. Studies of endogenous inhibitors of microsomal glutathione S-transferase.

    PubMed Central

    Boyer, T D; Zakim, D; Vessey, D A

    1982-01-01

    Glutathione S-transferase is present in rat liver microsomal fraction, but its activity is low relative to the transferase activity present in the soluble fraction of the hepatocyte. We have found, however, that the activity of microsomal glutathione S-transferase is increased 5-fold after treatment with small unilamellar vesicles made from phosphatidylcholine. The increase in activity is due to the removal of an inhibitor of the enzyme from the microsomal membrane. The inhibitor is present in the organic layer of a washed Folch extract of the microsomal fraction. When this fraction of the microsomal extract is reconstituted in the form of small unilamellar vesicles, it inhibits microsomal glutathione S-transferase that had been activated by prior treatment with small unilamellar vesicles of pure phosphatidylcholine, but does not affect the activity of unactivated microsomal glutathione S-transferase. The inhibitor did not seem to be formed during the isolation of the microsomal fraction, and hence may be a physiological regulator of microsomal glutathione S-transferase. In this regard, both free fatty acid (palmitate) and lysophosphatidylcholine were shown to inhibit the enzyme reversibly. The results indicate that the activity of microsomal glutathione S-transferase is far greater than appreciated until now, and that this form of the enzyme may be an important factor in the hepatic metabolism of toxic electrophiles. PMID:7181862

  1. Gata4 Is Essential for the Maintenance of Jejunal-Ileal Identities in the Adult Mouse Small Intestine?

    PubMed Central

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

    2006-01-01

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

  2. Effectiveness of a clinical pathway for inpatients undergoing ileal/ileocecal resection for chronic radiation enteritis with intestinal obstruction.

    PubMed

    Zhang, Liang; Gong, Jing-Feng; Dong, Jian-Ning; Zhu, Wei-Ming; Li, Ning; Li, Jie-Shou

    2015-03-01

    Surgery is associated with elevated morbidity and mortality in chronic radiation enteritis (CRE). The objective of this study was to evaluate the effect of a fast-track clinical pathway (CP) on postoperative outcomes in patients undergoing ileal/ileocecal resection for CRE with intestinal obstruction. There were 85 patients with CRE (January 2011 to March 2013) with intestinal obstruction admitted to our department for ileal/ileocecal resection. The patients were divided into a prepathway group and a pathway group. The clinical outcomes were then assessed and compared. The postoperative lengths of hospital stay were 8.52 days for the pathway group and 11.32 days for the prepathway group (P = 0.02). The pathway group had a lower stoma rate (21.6 vs 56%, P = 0.033) and fewer postoperative moderate to severe complications (8.1 vs 25%, P = 0.043) compared with the prepathway group. Implementation of the CP may reduce stoma rate, postoperative moderate to severe complications, and postoperative length of hospital stay for patients undergoing ileal/ileocecal resection for the treatment of CRE with intestinal obstruction. PMID:25760200

  3. Pathogenesis of mucosal biofilm infections: challenges and progress

    PubMed Central

    Dongari-Bagtzoglou, Anna

    2009-01-01

    Living-tissue biofilms remained unrecognized until very recently, mainly as a result of traditional microbial sampling techniques or histologic processing, which disrupt the spatial organization of the tissue microorganisms. Thus, the biofilm nature of certain mucosal infections was frequently unintentionally missed or disregarded. To a large extent, the study of human tissue biofilms is still in its infancy. However, with the advent of newer methodologies, such as fluorescent in situ hybridization and endoscopic confocal laser scanning microscopy, which combine the identification of microbes with in situ, direct visualization of their relationships with each other and with their substratum, mucosal tissue biofilms are becoming easier to study and, thus, their role in human infections is becoming more apparent. This review summarizes the challenges in the study of tissue biofilms, proposes two inflammation-centered – albeit opposite – pathogenetic models of mucosal tissue biofilm infections and suggests directions for future research and novel therapeutic approaches. PMID:18380602

  4. Mucosal vaccination by adenoviruses displaying reovirus sigma 1.

    PubMed

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

    2015-08-01

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

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

    PubMed Central

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

    2003-01-01

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

  6. Low level laser therapy may reduce risk of oral mucositis.

    PubMed

    Spivakovsky, Silvia

    2015-06-01

    Data sourcesMedline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), CINHAL, Web of Science, Scopus, LILACS, Conference proceedings of the International Society of Paediatric Oncology, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology and Oncology, and Multinational Association of Supportive Care in Cancer and the reference lists of identified studies.Study selectionTwo reviewers independently selected studies for inclusion with randomised controlled trials (RCTs) and quasi-RCTs being considered.Data extraction and synthesisData were extracted using a specifically developed form and study quality was assessed using the Cochrane risk of bias tool. Dichotomous outcomes data were synthesised using the risk ratio (RR) and 95% confidence interval (CI). Continuous outcomes measured using different scales were synthesised using the standardised mean difference (SMD) while those using the same scale were synthesised using the weighted mean difference (WMD).ResultsEighteen RCTs involving 1144 patients were included. Four trials were considered to be at low risk of bias across all domains. Prophylactic LLLT reduced the overall risk of severe mucositis (risk ratio (RR) 0.37, 95% confidence interval (CI) 0.20 to 0.67; P?=?0.001). Compared to placebo/no therapy LLLT also reduced the following outcomes; severe mucositis at the time of anticipated maximal mucositis RR = 0.34, (95% CI; 0.20 to 0.59); overall mean grade of mucositis SMD -1.49, (95% CI; -2.02 to -0.95); duration of severe mucositis WMD -5.32, 95% (CI; -9.45 to -1.19) and incidence of severe pain (RR 0.26, 95% CI; 0.18 to 0.37).ConclusionsProphylactic LLLT reduced severe mucositis and pain in patients with cancer and HSCT recipients. Future research should identify the optimal characteristics of LLLT and determine feasibility in the clinical setting. PMID:26114788

  7. 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.

  8. Modulation of cadmium-induced oxidative stress in Ceratophyllum demersum by zinc involves ascorbate–glutathione cycle and glutathione metabolism

    Microsoft Academic Search

    Parameswaran Aravind; Majeti Narasimha Vara Prasad

    2005-01-01

    To understand the interaction between Zn, an essential micronutrient and Cd, a non-essential element, Cd-10 ?M and Zn supplemented (10, 50, 100, and 200 ?M) Cd 10 ?M treated Ceratophyllum demersum L. (Coontail), a free floating freshwater macrophyte was chosen for the study. Cadmium at 10 ?M concentration decreased thiol content, enhanced oxidation of ascorbate (AsA) and glutathione (GSH) to dehydroascorbate (DHA) and glutathione

  9. Time course effects of vanadium supplement on cytosolic reduced glutathione level and glutathione S-transferase activity

    Microsoft Academic Search

    Anupam Bishayee; Malay Chatterjee

    1995-01-01

    The influence of vanadium, an important dietary micronutrient, was evaluated on the cytosolic reduced glutathione (GSH) content\\u000a and glutathione S-transferase (GST) activity in several rat target tissues. Supplementation of drinking water with vanadium\\u000a at the level of 0.2 or 0.5 ppm for 4, 8, or 12 wk was found to increase the GSH level with a concomitant elevation in GST

  10. Transient RNAi based gene silencing of glutathione synthetase reduces glutathione content in Camellia sinensis (L.) O. Kuntze somatic embryos

    Microsoft Academic Search

    P. Mohanpuria; N. K. Rana; S. K. Yadav

    2008-01-01

    We report on gene silencing of glutathione synthetase (GSHS) that reduces reduced glutathione (GSH) content in somatic embryos\\u000a of Camellia sinensis L. Using degenerate primers with cDNA of Camellia sinensis, a 457 bp GSHS gene fragment was cloned through polymerase chain reaction. This fragment was used in making ihpRNA. For this it was cloned\\u000a in sense at AscI and SwaI

  11. Spatial and Temporal Ontogenies of Glutathione Peroxidase and Glutathione Disulfide Reductase During Development of the Prenatal Rat

    Microsoft Academic Search

    Hyungsuk Choe; Jason M. Hansen; Craig Harris

    2001-01-01

    Spatial and temporal expression and regulation of the antioxidant enzymes, glutathione peroxidase (GSH-Px), glutathione disulfide reductase (GSSG-Rd) may be important in determining cell- specific susceptibility to embryotoxicants. Creation of tissue-specific ontogenies for antioxidant enzyme activities during development is an important first step in understanding regulatory relationships. Early organogenesis-stage embryos were grouped according to the somite number (GD 9-13), and fetuses

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

    PubMed

    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

  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. Ileal amino acids digestibility of sorghum in weaned piglets and growing pigs.

    PubMed

    Mariscal-Landín, G; Reis de Souza, T C; Avalos, M A

    2010-08-01

    The objective of the study was to determine the coefficients of ileal apparent digestibility (CIAD) of sorghum protein and amino acids (AA) in weaned piglets and growing pigs. Digestibility coefficients were estimated using the regression and difference methods for the weaned piglets; and the direct and difference methods for the growing pigs. To test the hypothesis that CP and AA digestibility of sorghum is lower in weaned piglets than in growing pigs, two experiments were conducted. In experiment one, 20 weaned piglets were fitted with a 'T' cannula at 21 days of age and were fed for 2 weeks one of five dietary treatments: a reference or control diet providing 200 g of CP/kg from casein (C) as the sole protein source, and four casein-sorghum (C-S) diets kept isoproteic to C by the appropriate adjustment of C and maize starch proportions; the amount of sorghum (S) in these diets was 135, 307, 460 and 614 g/kg. In experiment 2, fifteen castrated pigs weighing 57.8 ± 2.8 kg were used and randomly allotted to one of three dietary treatments: a reference casein-maize starch diet containing C as the sole protein source, a C-S diet, both diets containing 160 g of CP/kg, and a fortified S diet containing 68 g of CP/kg. In piglets the CIAD for CP and AA decreased linearly (P < 0.05) as the amount of S in the diet increased. The average ileal digestibility of AA from C was 0.858 ± 0.111, and decreased to 0.663 ± 0.191 at the higher S level. The CIAD estimated using the regression or difference methods were similar for leucine, cysteine, glutamic acid, serine, alanine and tyrosine, and different for the other AA. In growing pigs the CIAD of protein and AA (except alanine and cysteine) were similar (P > 0.05) for the C and the C-S diets, but higher (P < 0.05) than those for the S diet. The CIAD for S obtained by the difference method were higher (P < 0.05) than those obtained using the direct method, except for lysine, isoleucine, valine, methionine, threonine and cysteine. The results indicate that except for lysine and cysteine, growing pigs' ability to digest AA and protein is superior than weaned piglets. PMID:22444654

  15. Fermentable non-starch polysaccharides increases the abundance of Bacteroides-Prevotella-Porphyromonas in ileal microbial community of growing pigs.

    PubMed

    Ivarsson, E; Roos, S; Liu, H Y; Lindberg, J E

    2014-11-01

    Most plant-origin fiber sources used in pig production contains a mixture of soluble and insoluble non-starch polysaccharides (NSP). The knowledge about effects of these sources of NSP on the gut microbiota and its fermentation products is still scarce. The aim of this study was to investigate effects of feeding diets with native sources of NSP on the ileal and fecal microbial composition and the dietary impact on the concentration of short-chain fatty acids (SCFA) and lactic acid. The experiment comprised four diets and four periods in a change-over design with seven post valve t-cecum cannulated growing pigs. The four diets were balanced to be similar in NSP content and included one of four fiber sources, two diets were rich in pectins, through inclusion of chicory forage (CFO) and sugar beet pulp, and two were rich in arabinoxylan, through inclusion of wheat bran (WB) and grass meal. The gut microbial composition was assessed with terminal restriction fragment (TRF) length polymorphism and the abundance of Lactobacillus spp., Enterobacteriaceae, Bacteroides-Prevotella-Porphyromonas and the ?-xylosidase gene, xynB, were assessed with quantitative PCR. The gut microbiota did not cluster based on NSP structure (arabinoxylan or pectin) rather, the effect was to a high degree ingredient specific. In pigs fed diet CFO, three TRFs related to Prevotellaceae together consisted of more than 25% of the fecal microbiota, which is about 3 to 23 times higher (P<0.05) than in pigs fed the other diets. Whereas pigs fed diet WB had about 2 to 22 times higher abundance (P<0.05) of Megasphaera elsdenii in feces and about six times higher abundance (P<0.05) of Lactobacillus reuteri in ileal digesta than pigs fed the other diets. The total amount of digested NSP (r=0.57; P=0.002), xylose (r=0.53; P=0.004) and dietary fiber (r=0.60; P=0.001) in ileal digesta were positively correlated with an increased abundance of Bacteroides-Prevotella-Porphyromonas. The effect on SCFA was correlated to specific neutral sugars where xylose increased the ileal butyric acid proportion, whereas arabinose increased the fecal butyric acid proportion. Moreover, chicory pectin increased the acetic acid proportion in both ileal digesta and feces. PMID:25046106

  16. Altered glutathione homeostasis in animals prenatally exposed to lipopolysaccharide

    PubMed Central

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

    2007-01-01

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

  17. Mucosal adjuvants and delivery systems for protein-, DNA and RNA-based vaccines

    Microsoft Academic Search

    Michael Vajdy; Indresh Srivastava; John Polo; John Donnelly; Derek O'Hagan; Manmohan Singh

    2004-01-01

    Almost all vaccinations today are delivered through parenteral routes. Mucosal vaccination offers several benefits over parenteral routes of vaccination, including ease of administration, the possibility of self-administration, elimination of the chance of injection with infected needles, and induction of mucosal as well as systemic immunity. However, mucosal vaccines have to overcome several formidable barriers in the form of significant dilution

  18. Effects of blood glucose levels on aspirin-induced gastric mucosal damage

    Microsoft Academic Search

    A. Macdonald; J. B. Dekanski; S. Gottfried; D. V. Parke; P. Sacra

    1977-01-01

    In female rats aspirin-induced gastric mucosal damage was increased and glycoprotein synthesis decreased by fasting and by insulin administration. Glucose added to the drinking water during the fasting period reduced mucosal damage and increased glycoprotein synthesis to control levels. Alloxan diabetes did not affect mucosal damage or glycoprotein synthesis. Alloxan diabetes plus insulin restored blood glucose levels to normal, and

  19. Regional specialization in the mucosal immune system: what happens in the microcompartments?

    Microsoft Academic Search

    Per Brandtzaeg; Espen S Baekkevold; Inger N Farstad; Frode L Jahnsen; Finn-Eirik Johansen; Ellen M Nilsen; Takeshi Yamanaka

    1999-01-01

    Mucosal immunity is an important arm of the immune system because it operates in tissues involved in everyday infectious defence as well as in tolerance against innocuous environmental and dietary antigens. Here, Per Brandtzaeg and colleagues discuss compartmentalized regulation of mucosal B cells and mechanisms that might explain the strikingly regionalized effector disparity of the human mucosal immune system.

  20. Prophylaxis and treatment of chemo- and radiotherapy-induced oral mucositis – are there new strategies?

    Microsoft Academic Search

    M Karthaus; C Rosenthal; A Ganser

    1999-01-01

    Oral mucositis is a major dose-limiting toxic effect of intensive cancer chemotherapy. Oral complications may lead to dose reduction or delay in further cancer treatment. Mucositis can be caused directly by cytotoxic effects and indirectly by sustained neutropenia after cytostatic therapy. An impaired mucosal barrier predisposes to life-threatening septic complications during aplasia. The prevalence of an oral focus in febrile

  1. K? absorption by locust gut and inhibition of ileal K? and water transport by FGLamide allatostatins.

    PubMed

    Robertson, Lisa; Donini, Andrew; Lange, Angela B

    2014-09-15

    The scanning ion-selective electrode technique (SIET) was utilized for the first time in Locusta migratoria to characterize K(+) transport along the digestive tract and to determine the effect of two locust FGLamide allatostatins (FGLa/ASTs) on K(+) transport: a previously sequenced FGLa/AST from Schistocerca gregaria (Scg-AST-6; ARPYSFGL-NH2) and a newly sequenced FGLa/AST from L. migratoria (Locmi-FGLa/AST-2; LPVYNFGL-NH2). Regional differences in K(+) fluxes along the gut were evident, where K(+) efflux in vitro (or absorption into the hemolymph in vivo) was greatest at the anterior ileum, and lowest at the colon. Ileal K(+) efflux was inhibited by both Scg-AST-6 and Locmi-FGLa/AST-2, with maximal inhibition at 10(-10) and 10(-11) mol l(-1), respectively. Both FGLa/ASTs also inhibited cAMP-stimulated K(+) efflux from the ileum. Locmi-FGLa/AST-2 also inhibited efflux of water across the ileum. Locusts are terrestrial insects living in dry climates, risking desiccation and making water conservation a necessity. The results suggest that FGLa/ASTs may be acting as diuretics by increasing K(+) excretion and therefore increasing water excretion. Thus it is likely that FGLa/ASTs are involved in the control of hemolymph water and ion levels during feeding and digestion, to help the locust deal with the excess K(+) load (and subsequently fluid) when the meal is processed. PMID:25013112

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

    PubMed Central

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

    2011-01-01

    Background and Aims Both deoxynivalenol (DON) and nontyphoidal salmonellosis are emerging threats with possible hazardous effects on both human and animal health. The objective of this study was to examine whether DON at low but relevant concentrations interacts with the intestinal inflammation induced by Salmonella Typhimurium. Methodology By using a porcine intestinal ileal loop model, we investigated whether intake of low concentrations of DON interacts with the early intestinal inflammatory response induced by Salmonella Typhimurium. Results A significant higher expression of IL-12 and TNF? and a clear potentiation of the expression of IL-1?, IL-8, MCP-1 and IL-6 was seen in loops co-exposed to 1 µg/mL of DON and Salmonella Typhimurium compared to loops exposed to Salmonella Typhimurium alone. This potentiation coincided with a significantly enhanced Salmonella invasion in and translocation over the intestinal epithelial IPEC-J2 cells, exposed to non-cytotoxic concentrations of DON for 24 h. Exposure of Salmonella Typhimurium to 0.250 µg/mL of DON affected the bacterial gene expression level of a limited number of genes, however none of these expression changes seemed to give an explanation for the increased invasion and translocation of Salmonella Typhimurium and the potentiated inflammatory response in combination with DON. Conclusion These data imply that the intake of low and relevant concentrations of DON renders the intestinal epithelium more susceptible to Salmonella Typhimurium with a subsequent potentiation of the inflammatory response in the gut. PMID:21909370

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

    PubMed Central

    Annaba, Fadi; Kumar, Pradeep; Dudeja, Amish K.; Saksena, Seema; Gill, Ravinder K.

    2010-01-01

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

  4. Calprotectin Expression Inhibits Bacterial Binding to Mucosal Epithelial Cells

    Microsoft Academic Search

    KANOKWAN NISAPAKULTORN; KAREN F. ROSS; MARK C. HERZBERG

    2001-01-01

    Squamous mucosal epithelial cells constitutively express calprotectin in the cytoplasm. To study how this antimicrobial protein complex confers epithelial resistance to invading bacteria, an epithelial cell line was stably transfected to express the calprotectin complex. Cells expressing calprotectin resist invasion by Listeria monocytogenes and Salmonella enterica serovar Typhimurium. Calprotectin expression was accompanied by altered actin organization, increased a3 integrin expression,

  5. Endoscopic mucosal resection for treatment of early gastric cancer

    Microsoft Academic Search

    H Ono; H Kondo; T Gotoda; K Shirao; H Yamaguchi; D Saito; K Hosokawa; T Shimoda; S Yoshida

    2001-01-01

    BACKGROUNDIn Japan, endoscopic mucosal resection (EMR) is accepted as a treatment option for cases of early gastric cancer (EGC) where the probability of lymph node metastasis is low. The results of EMR for EGC at the National Cancer Center Hospital, Tokyo, over a 11 year period are presented.METHODSEMR was applied to patients with early cancers up to 30 mm in

  6. C-kit expression in canine mucosal melanomas.

    PubMed

    Newman, S J; Jankovsky, J M; Rohrbach, B W; LeBlanc, A K

    2012-09-01

    The c-kit receptor is responsible for transmission of promigration signals to melanocytes; its downregulation may be involved in malignant progression of human melanocytic neoplasms. Expression of this receptor has not been examined in normal or neoplastic melanocytes from dogs. In this study, 14 benign dermal and 61 malignant mucosal melanocytic tumors were examined for c-kit (KIT) expression. Sites of the mucosal melanomas were gingiva (not further specified; n = 30), buccal gingiva (n = 6), soft palate (n = 4), hard palate (n = 5), tongue (n = 7), lip (n = 6), and conjunctiva (n = 3). Melan A was expressed in all 14 dermal melanocytomas and in 59 of 61 (96.7%) tumors from oral or conjunctival mucosa, confirming melanocytic origin. C-kit receptor expression was strong and diffuse throughout the cytoplasm in all 14 dermal melanocytomas and was identified in basilar mucosal melanocytes over submucosal neoplasms (27 of 61, 44.3%), junctional (neoplastic) melanocytes (17 of 61, 27.9%), and, less commonly, neoplastic melanocytes of the subepithelial tumors (6 of 61, 9.8%). KIT expression anywhere within the resected melanomas correlated with significantly longer survival. These results suggest that c-kit receptor expression may be altered in canine melanomas and may have potential as a prognostic indicator for mucosal melanomas. PMID:21825314

  7. Heparanase expression correlates with poor survival in oral mucosal melanoma.

    PubMed

    Wang, Xin; Wen, Weiwei; Wu, Heming; Chen, Yi; Ren, Guoxin; Guo, Wei

    2013-01-01

    Oral mucosal melanoma (OMM) is a lethal cancer with a poor prognosis. Despite the great interest in heparanase (HPSE) as a potential anticancer therapy target, the prognostic role of HPSE in oral mucosal melanoma has not been elucidated. In this study, we investigated HPSE expression in OMM tissues and examined its association with clinical outcome. A total of 81 patients with OMM were enrolled in this study. We examined the expression of HPSE in OMM, and its staining extent, intensity and cellular localization were analyzed for clinical significance. HPSE staining was positive in 81 % of tumors (66 of 81 patients) and was negative in the remaining 19 % (15 patients). The median survival time and the 5-year survival rate were 12 months and 7.0 % in the high-heparanase group, 35 months and 36.4 % in the low-heparanase group and 62 months and 53.3 % in the none-heparanase group (P = 0.001). In univariate survival analysis of oral mucosal melanoma, AJCC Stage, heparanase level, heparanase location and tumor size were the clinical parameters related to overall survival. In Cox analysis, overall survival time was significantly dependent on AJCC stage and heparanase level, but not tumor size and heparanase location. Heparanase is frequently expressed in oral mucosal melanoma, and its expression levels inversely correlate with the survival rates of OMM patients, clearly indicating that heparanase is a reliable prognostic factor for this malignancy and an attractive target for anticancer drug development. PMID:23794232

  8. Activation of the mucosal immune system in irritable bowel syndrome

    Microsoft Academic Search

    Vinton S. Chadwick; Wangxue Chen; Dairu Shu; Barbara Paulus; Peter Bethwaite; Andy Tie; Ian Wilson

    2002-01-01

    Background & Aims: A role for the mucosal immune system in the pathogenesis of irritable bowel syndrome is suggested by its association with intestinal infections. Methods: To investigate this, we performed histologic and immunohistologic studies on colonoscopic biopsy specimens from 77 patients with symptoms satisfying the Rome criteria and 28 asymptomatic control patients. Results: Histologic assessment of biopsy specimens from

  9. Candida albicans interactions with epithelial cells and mucosal immunity

    PubMed Central

    Naglik, Julian R.; Moyes, David L; Wächtler, Betty; Hube, Bernhard

    2011-01-01

    Candida albicans interactions with epithelial cells are critical for commensal growth, fungal pathogenicity and host defence. This review will outline our current understanding of C. albicans-epithelial interactions and will discuss how this may lead to the induction of a protective mucosal immune response. PMID:21801848

  10. Human Mucosal Associated Invariant T Cells Detect Bacterially Infected Cells

    E-print Network

    Paris-Sud XI, Université de

    Human Mucosal Associated Invariant T Cells Detect Bacterially Infected Cells Marielle C. Gold1 frequency Mtb-reactive CD8+ T cells are present in both Mtb-infected and uninfected humans. We show with Mycobacterium tuberculosis (Mtb) requires Th1-type immunity, of which CD8+ T cells play a unique role. High

  11. Mucosal Biofilm Communities in the Human Intestinal Tract

    Microsoft Academic Search

    Sandra Macfarlane; Bahram Bahrami; George T. Macfarlane

    2011-01-01

    Complex and highly variable site-dependent bacterial ecosystems exist throughout the length of the human gastrointestinal tract. Until relatively recently, the majority of our information on intestinal microbiotas has come from studies on feces, or from aspirates taken from the upper gut. However, there is evidence showing that mucosal bacteria growing in biofilms on surfaces lining the gut differ from luminal

  12. Postdoctoral Research Positions in Mucosal Immunology and Molecular Microbiology

    E-print Network

    Symington, Lorraine S.

    Postdoctoral Research Positions in Mucosal Immunology and Molecular Microbiology Two post-doctoral research positions are available at the Department of Microbiology and Immunology, Columbia University, New the challenge of working at the interface between Immunology and Microbiology. The selected candidates will work

  13. Neuroselective Current Perception Threshold Evaluation of Bladder Mucosal Sensory Function

    Microsoft Academic Search

    Osamu Ukimura; So Ushijima; Hisashi Honjo; Tsuyoshi Iwata; Kei Suzuki; Naoki Hirahara; Koji Okihara; Yoichi Mizutani; Akihiro Kawauchi; Tsuneharu Miki

    2004-01-01

    Objective: To evaluate human bladder mucosal sensory function by neuroselective Current Perception Threshold (CPT) measures from healthy and neuropathic bladders.Methods: Eight healthy volunteers and 38 patients with urinary symptoms underwent conventional urodynamic tests including water-filling cystometry and ice water test. Standardized neuroselective CPT measures were obtained from the left index finger and the mucosa of the posterior bladder wall. Three

  14. Pulmonary-intestinal cross-talk in mucosal inflammatory disease

    Microsoft Academic Search

    S Keely; N J Talley; P M Hansbro

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases (IBDs) are chronic inflammatory diseases of mucosal tissues that affect the respiratory and gastrointestinal tracts, respectively. They share many similarities in epidemiological and clinical characteristics, as well as in inflammatory pathologies. Importantly, both conditions are accompanied by systemic comorbidities that are largely overlooked in both basic and clinical research. Therefore, consideration

  15. Congenital Oral Mucosal Abnormalities in True Umbilical Cord Knots

    Microsoft Academic Search

    Claudio De Felice; Giorgio Bianciardi; Stefano Parrini; Ricardo N. Laurini; Giuseppe Latini

    2004-01-01

    Objective: The pathogenesis and clinical significance of true umbilical cord knots remain controversial. Here, we tested the hypothesis of the presence of congenital oral mucosal changes in newborns with true umbilical cord knots. Study design: Seven consecutive infants with true umbilical cord knots and 50 gestational age- and sex-matched controls were enrolled. The proportion of oral frenulum abnormalities and the

  16. Mucosal immunity--a major adaptive defence mechanism.

    PubMed

    Brandtzaeg, P; Berstad, A E; Farstad, I N; Haraldsen, G; Helgeland, L; Jahnsen, F L; Johansen, F E; Natvig, I B; Nilsen, E M; Rugtveit, J

    1997-02-01

    The epithelial glycoprotein called secretory component (SC) is quantitatively the most important receptor of the immune system because it is responsible for external transport of locally produced polymeric IgA (pIgA) to generate remarkably large amounts of secretory IgA. Antibodies of this type constitute the major mediators of specific humoral immunity. Transmembrane SC belongs to the Ig supergene family and functions as a common pIg receptor, also translocating pentameric IgM externally to form secretory IgM. The B cells responsible for mucosal pIg production are initially stimulated in organized mucosa-associated lymphoepithelial structures, particularly the Peyer's patches in the distal small intestine; from these inductive site they migrate as memory cells to exocrine tissues all over the body. Mucous membranes are thus furnished with secretory antibodies in an integrated way, ensuring a variety of specificities at every secretory effector site. There is currently great interest in exploiting this integrated or "common" mucosal immune system for oral vaccination against pathogenic infectious agents and also to induce tolerance in T cell-mediated autoimmune diseases. However, much remains to be learned about mechanisms for antigen uptake and processing necessary to elicit stimulatory or suppressive mucosal immune responses. Moreover, evidence is emerging for the existence of considerable regionalization with regard to functional links between inductive sites and effecter sites of mucosal immunity. PMID:9382729

  17. Differential Injury Responses in Oral Mucosal and Cutaneous Wounds

    Microsoft Academic Search

    A. M. Szpaderska; J. D. Zuckerman; L. A. DiPietro

    2003-01-01

    Oral mucosa heals faster than does skin, yet few studies have compared the repair at oral mucosal and cutaneous sites. To determine whether the privileged healing of oral injuries involves a differential inflammatory phase, we compared the inflammatory cell infiltrate and cytokine production in wounds of equivalent size in oral mucosa and skin. Significantly lower levels of macrophage, neutrophil, and

  18. Inflammatory Monocytes Are Required for Mucosal Resistance to the Pathogen

    E-print Network

    Arnold, Jonathan

    Immunity Article Gr1+ Inflammatory Monocytes Are Required for Mucosal Resistance to the Pathogen in the murine model. We demonstrated that after oral infection, the parasite rapidly recruited in- flammatory susceptible to oral toxoplasmosis. Col- lectively, these findings illustrate the critical impor- tance

  19. Depleted mucosal antioxidant defences in inflammatory bowel disease

    Microsoft Academic Search

    Gary D. Buffinton; William F. Doe

    1995-01-01

    Experimental approaches designed to define the role of reactive oxygen and nitrogen species generated by inflammatory cells in the tissue injury seen in inflammatory bowel disease rarely consider the chemical antioxidant defences against such increased oxidant stress in the mucosa. In this investigation, we have analysed components of the aqueous and lipid phase antioxidant mucosal defences by measuring the total

  20. Pharmacological Protection From Radiation {+-} Cisplatin-Induced Oral Mucositis

    SciTech Connect

    Cotrim, Ana P. [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Yoshikawa, Masanobu [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa (Japan); Sunshine, Abraham N.; Zheng Changyu [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Sowers, Anastasia L.; Thetford, Angela D.; Cook, John A.; Mitchell, James B. [Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Baum, Bruce J., E-mail: bbaum@dir.nidcr.nih.gov [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)

    2012-07-15

    Purpose: To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation {+-} cisplatin. Methods and Materials: Female C3H mice, {approx}8 weeks old, were irradiated with five fractionated doses {+-} cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured. Results: Significant lingual ulcers resulted from 5 Multiplication-Sign 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. Conclusions: Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.

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

    SciTech Connect

    Smith, Allen D. [Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705 (United States)]. E-mail: smitha@ba.ars.usda.gov; Dawson, Harry [Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705 (United States)]. E-mail: dawsonh@ba.ars.usda.gov

    2006-09-30

    Glutathione is an intracellular reducing agent that helps maintain the redox potential of the cell and is important for immune function. The drug L-buthionine sulfoximine (BSO) selectively inhibits glutathione synthesis. Glutathione has been reported to block replication of HIV, HSV-1, and influenza virus, whereas cells treated with BSO exhibit increased replication of Sendai virus. Pre-treatment of HeLa cell monolayers with BSO inhibited replication of CVB3, CVB4, and HRV14 with viral titers reduced by approximately 6, 5, and 3 log{sub 1}, respectively. The addition of glutathione ethyl ester, but not dithiothreitol or 2-mercaptoethanol, to the culture medium reversed the inhibitory effect of BSO. Viral RNA and protein synthesis were not inhibited by BSO treatment. Fractionation of lysates from CVB3-infected BSO-treated cells on cesium chloride and sucrose gradients revealed that empty capsids but not mature virions were being produced. The levels of the 5S and 14S assembly intermediates, however, were not affected by BSO treatment. These results demonstrate that glutathione is important for production of mature infectious picornavirus virions.

  2. Genetic Analysis of Tissue Glutathione Concentrations and Redox Balance

    PubMed Central

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

    2014-01-01

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

  3. Purification and characterisation of chicken liver monomeric glutathione peroxidase.

    PubMed

    Miyazaki, S; Motoi, Y

    1996-07-01

    1. A novel glutathione peroxidase, which is distinct from tetrameric glutathione peroxidase, was purified to homogeneity from a broiler chick liver cytosolic fraction using 5 different column chromatographic methods. 2. The enzyme in cytosol was separated from 'classic' tetrameric glutathione peroxidase and glutathione S-transferases by DEAE-Sephacel and Sephadex G-100 chromatographies and further purified by Mono Q hydroxylapatite and sulphobromophthalein-S-glutathione-agarose chromatographies. 3. The molecular weight of the purified enzyme determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis was 19,500 and that found by gel filtration chromatography was comparable. This indicates that the enzyme protein is a single polypeptide. The isoelectric point of the enzyme was determined as 7.0 by polyacrylamide gel isoelectric focusing. 4. The purified enzyme catalysed the reduction of hydrogen peroxide, cumene hydroperoxide, text-butyl hydroperoxide and linoleic acid hydroperoxide. Furthermore, it reduced phosphatidylcholine hydroperoxide in the absence of phospholipase A2. The optimum pH for the enzyme reaction was 7.0. The antiserum against the purified enzyme reacted with the 19.5 kDa polypeptide in the liver cytosol of duck and quail. PMID:8842471

  4. Oral health as a predictive factor for oral mucositis

    PubMed Central

    Coracin, Fabio Luiz; da Silva Santos, Paulo Sergio; Gallottini, Marina H. C.; Saboya, Rosaura; Musqueira, Priscila Tavares; Barban, Alessandra; de Alencar Fischer Chamone, Dalton; Dulley, Frederico Luiz; Nunes, Fabio Daumas

    2013-01-01

    OBJECTIVES: Oral mucositis is a complication frequently associated with hematopoietic stem cell transplantation, decreasing a patient's quality of life and increasing the occurrence of opportunistic infections. The purpose of this study was to determine the incidence and severity of oral mucositis and to assess the correlation of this disease with the oral health of an individual at the time of hematopoietic stem cell transplantation. METHODS: Before transplantation, patients' oral health and inflammatory conditions were determined using the gingival index and the plaque index, which are based on gingival bleeding and the presence of dental plaque, respectively. Additionally, the dental health status was determined using the decayed, missing, and filled teeth index. The monitoring of oral mucositis was based on the World Health Organization grading system and was performed for five periods: from Day 0 to D+5, from D+6 to D+10, from D+11 to D+15, from D+16 to D+20, and from D+21 to D+30. RESULTS: A total of 97 patients (56% male and 44% female) who underwent hematopoietic stem cell transplantation at the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo between January 2008 and July 2009 were prospectively examined. The incidence of ulcerative mucositis was highest from days +6 to +10 and from days +11 to +15 in the patients who underwent autologous and allogeneic hematopoietic stem cell transplantation, respectively. CONCLUSION: The data, including the dental plaque and periodontal status data, showed that these oral health factors were predictive of the incidence and severity of oral mucositis in a cohort of patients with similar conditioning regimens before hematopoietic stem cell transplantation. PMID:23778491

  5. Mucosal immunity and protection against HIV/SIV infection: strategies and challenges for vaccine design

    PubMed Central

    Demberg, Thorsten; Robert-Guroff, Marjorie

    2012-01-01

    To date most HIV vaccine strategies have focused on parenteral immunization and systemic immunity. These approaches have not yielded the efficacious HIV vaccine urgently needed to control the AIDS pandemic. As HIV is primarily mucosally transmitted, efforts are being refocused on mucosal vaccine strategies, in spite of complexities of immune response induction and evaluation. Here we outline issues in mucosal vaccine design and illustrate strategies with examples from the recent literature. Development of a successful HIV vaccine will require in depth understanding of the mucosal immune system, knowledge that ultimately will benefit vaccine design for all mucosally transmitted infectious agents. PMID:19241252

  6. The oxido-reductase enzyme glutathione peroxidase 4 (GPX4) governs Salmonella?Typhimurium-induced neutrophil transepithelial migration

    PubMed Central

    Agbor, Terence A; Demma, Zachary; Mrsny, Randall J; Castillo, Antonio; Boll, Erik J; McCormick, Beth A

    2014-01-01

    Summary Neutrophil (polymorphonuclear leucocytes; PMN) transmigration across mucosal surfaces contributes to dysfunction of epithelial barrier properties, a characteristic underlying many mucosal inflammatory diseases. Using Salmonella enterica serovar Typhimurium (S. Typhimurium) as a prototypic proinflammatory insult, we have previously reported that the eicosanoid hepoxilin A3 (HXA3), an endogenous product of 12-lipoxygenase (12-LOX) activity, is secreted from the apical surface of the intestinal epithelium to establish a chemotactic gradient that guides PMN across the epithelial surface. Since little is known regarding the molecular mechanisms that regulate 12-LOX during S. Typhimurium infection, we investigated this pathway. We found that expression of phospholipid glutathione peroxidase (GPX4), which is known to have an inhibitory effect on 12-LOX activity, is significantly decreased at both the mRNA and protein level during infection with S. Typhimurium. Moreover, employing intestinal epithelial cell monolayers expressing siRNA against GPX4 mRNA, S. Typhimurium-induced PMN migration was significantly increased compared with the non-specific siRNA control cells. Conversely, in cells engineered to overexpress GPX4, S. Typhimurium-induced PMN migration was significantly decreased, which is consistent with the finding that partial depletion of GPX4 by RNAi resulted in a significant increase in HXA3 secretion during S. Typhimurium infection. Mechanistically, although we found Salmonella entry not to be required for the induced decrease in GPX4, the secreted effector, SipA, which is known to induce epithelial responses leading to stimulation of HXA3, governed the decrease in GPX4 in a process that does not lead to an overall increase in the levels of ROS. Taken together, these results suggest that S. Typhimurium induces apical secretion of HXA3 by decreasing the expression of phospholipid GPX, which in turn leads to an increase in 12-LOX activity, and hence HXA3 synthesis. PMID:24617613

  7. 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

  8. The efficacy of sucralfate suspension in the prevention of oral mucositis due to radiation therapy

    SciTech Connect

    Epstein, J.B.; Wong, F.L.W. (British Columbia Cancer Agency, Vancouver (Canada))

    1994-02-01

    The purpose of this study was to assess the value of sucralfate suspension in prevention of oral mucositis and for reduction of oral pain in patients who develop mucositis during radiation therapy. The study was a double-blind, placebo-controlled, randomized prospective trial of a sucralfate suspension in the prevention and management of oral mucositis during radiation therapy. Oral mucositis was assessed using a quantitative scale and symptoms were assessed using visual analogue scales. The statistical model was developed to detect a 40% reduction in mucositis. No statistically significant reduction in mucositis was seen. Early during radiation therapy less oral pain was reported in the sucralfate group, but as treatment progressed all patients experienced pain. Patients in the sucralfate group were prescribed topical and systemic analgesics later in the course of radiation therapy. Prophylactic oral rinsing with sucralfate did not prevent oral ulcerative mucositis. Sucralfate may reduce the experience of pain during radiation therapy. 32 refs., 3 tabs.

  9. Dark Agouti rat model of chemotherapy-induced mucositis: Establishment and current state of the art.

    PubMed

    Vanhoecke, Barbara; Bateman, Emma; Mayo, Bronwen; Vanlancker, Eline; Stringer, Andrea; Thorpe, Daniel; Keefe, Dorothy

    2015-06-01

    Mucositis is a major oncological problem. The entire gastrointestinal and genitourinary tract and also other mucosal surfaces can be affected in recipients of radiotherapy, and/or chemotherapy. Major progress has been made in recent years in understanding the mechanisms of oral and small intestinal mucositis, which appears to be more prominent than colonic damage. This progress is largely due to the development of representative laboratory animal models of mucositis. This review focuses on the development and establishment of the Dark Agouti rat mammary adenocarcinoma model by the Mucositis Research Group of the University of Adelaide over the past 20 years to characterize the mechanisms underlying methotrexate-, 5-fluorouracil-, and irinotecan-induced mucositis. It also aims to summarize the results from studies using different animal model systems to identify new molecular and cellular markers of mucositis. PMID:25966981

  10. Mucosal vaccination against diphtheria using starch microparticles as adjuvant for cross-reacting material (CRM197) of diphtheria toxin

    Microsoft Academic Search

    Niclas Rydell; Ingvar Sjöholm

    2005-01-01

    Mucosal vaccination has the advantage of eliciting a local mucosal immune response as well as a systemic response. In this investigation, polyacryl starch microparticles were conjugated to diphtheria toxin cross-reacting material (CRM197) as a mucosal adjuvant for oral or intranasal immunisation of mice. Various methods of stabilising CRM197 with formaldehyde were investigated. A good systemic and local mucosal immune response

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

    SciTech Connect

    Gao Weihua [Toxicogenomics Informatics Project, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 (Japan); Mizukawa, Yumiko [Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto 610-0395 (Japan); Nakatsu, Noriyuki; Minowa, Yosuke; Yamada, Hiroshi [Toxicogenomics Informatics Project, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 (Japan); Ohno, Yasuo [National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-Ku, Tokyo, 158-8501 (Japan); Urushidani, Tetsuro, E-mail: turushid@dwc.doshisha.ac.j [Toxicogenomics Informatics Project, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 (Japan); Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto 610-0395 (Japan)

    2010-09-15

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

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

    PubMed

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

    2012-12-01

    Seven post-valve T-caecum cannulated growing pigs were used in a change-over experiment with four diets and four 14-day periods to evaluate the total tract apparent digestibility (TTAD) and the ileal apparent digestibility (IAD) of diets with inclusion of chicory forage (CFO), sugar beet pulp (SBP), wheat bran (WB) and grass meal (GM), as well as the TTAD of the mentioned fibre sources. Moreover, this experiment evaluated the molecular weight distribution of soluble non-starch polysaccharide (NSP) fractions in diet and ileal digesta from pigs fed the CFO and SBP diets. The experimental diets were balanced to have similar NSP content and compromised of one part of the basal diet and one part of the four fibre sources (CFO, SBP, WB and GM). In addition, all pigs were fed the basal diet during a 14-day period before and after the experimental periods. Diet affected the TTAD of all dietary components except glucose. The TTAD of organic matter (OM) was higher for Diet SBP than for Diets WB and CFO, showing both were higher than Diet GM. The TTAD of NSP was higher for Diet SBP than Diets WB and GM. The IAD of OM was higher in Diet SBP than in the other diets. The IAD of NSP was lower in Diet WB than in the other diets. The TTAD of OM and energy of CFO was 0.43 ± 0.04 (standard error), which is similar to that reported for commonly used forage crops. The molecular weight distribution in ileal digesta showed different distributions between Diets CFO and SBP as well as between digesta from pigs fed these diets. PMID:23130965

  13. 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. PMID:24570464

  14. The use of 15N-labeled dietary proteins for determining true ileal amino acid digestibilities is limited by their rapid recycling in the endogenous secretions of pigs.

    PubMed

    Leterme, P; Théwis, A; François, E; Van Leeuwen, P; Wathelet, B; Huisman, J

    1996-09-01

    We assessed the use of 15N-labeled dietary proteins as a possible tool for the determination of the true ileal amino acid (AA) digestibility in pigs. The first experiment was designed to study the dietary N excretion pattern at the ileum subsequent to the ingestion of a single 15N-labeled meal. In a second experiment, we compared ileal endogenous AA outputs and true AA digestibility estimates obtained in pigs ingesting 15N-labeled dietary proteins in a single meal vs. intravenous infusion of [15N]leucine for 10 d during the ingestion of a pea-based diet and a protein-free starch diet. The proportion of endogenous N found in the ileal digesta differed when the label was delivered orally (50%) vs. intravenously (72%) and changed with time. As a consequence, the true ileal AA digestibilities measured with labeled diets were lower. A third experiment demonstrated that this was due to the rapid recycling of labeled dietary N in endogenous moieties, because 15N was found in blood within 10 min of consuming the labeled meal, within 50 min of consumption in pancreatic enzymes, 90 min in bile and 4 h in ileal mucins. We conclude that the use of 15N-labeled meals for determination of true ileal AA digestibilities is limited by the fast recycling of dietary N in endogenous secretions following a single 15N-labeled meal. The accuracy of results will depend on meaningful estimates of AA flow during a limited period and accurate estimates of 15N in AA. PMID:8814207

  15. Beneficial effects of Camellia Oil (Camellia oleifera Abel.) on ketoprofen-induced gastrointestinal mucosal damage through upregulation of HO-1 and VEGF.

    PubMed

    Cheng, Yu-Ting; Wu, Shu-Li; Ho, Cheng-Ying; Huang, Shang-Ming; Cheng, Chun-Lung; Yen, Gow-Chin

    2014-01-22

    Nonsteroidal anti-inflammatory drugs, such as ketoprofen, are generally used to treat pain and inflammation and as pyretic agents in clinical medicine. However, the usage of these drugs may lead to oxidative injury to the gastrointestinal mucosa. Camellia oil ( Camellia oleifera Abel.) is commonly used in Taiwan and China as cooking oil. Traditional remedies containing this oil exert beneficial health effects on the bowel, stomach, liver, and lungs. However, the effects of camellia oil on ketoprofen-induced oxidative gastrointestinal mucosal lesions remain unknown. The objective of this study was to evaluate the effect of camellia oil on ketoprofen-induced acute gastrointestinal ulcers. The results showed that treatment of Int-407 cells with camellia oil (50-75 ?g/mL) not only increased the levels of heme oxygenase-1 (HO-1), glutathione peroxidase (GPx), and superoxide dismutase (SOD) mRNA expression but also increased vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) protein secretion, which served as a mucosal barrier against gastrointestinal oxidative injury. Moreover, Sprague-Dawley (SD) rats treated with camellia oil (2 mL/kg/day) prior to the administration of ketoprofen (50 mg/kg/day) successfully inhibited COX-2 protein expression, inhibited the production of interleukin-6 (IL-6) and nitrite oxide (NO), reversed the impairment of the antioxidant system, and decreased oxidative damage in the gastrointestinal mucosa. More importantly, pretreatment of SD rats with camellia oil strongly inhibited gastrointestinal mucosal injury induced by ketoprofen, which was proved by the histopathological staining of gastrointestinal tissues. Our data suggest that camellia oil exerts potent antiulcer effects against oxidative damage in the stomach and intestine induced by ketoprofen. PMID:24377395

  16. Rectal eversion and double-stapled ileal pouch anal anastomosis in familial adenomatous polyposis syndrome

    PubMed Central

    Aygar, Muhittin; Yeti?ir, Fahri; Salman, Ebru; Y?ld?r?m, Murat Baki; Özdedeo?lu, Mesut; Durak, Do?ukan; Yalç?n, Abdussamet

    2014-01-01

    INTRODUCTION Surgery is the only treatment option for familial adenomatous polyposis (FAP). Aim of surgery in FAP is to minimize colorectal cancer risk without need for permanent stoma. There are especially two operation options; Total colectomy with ileorectal anastomosis (IRA) and total proctocolectomy with ileo-pouch anal anastomosis (IPAA). We report here a patient with FAP who had resection via rectal eversion just over the dentate line under direct visualization and ileoanal-J pouch anastomosis by double-stapler technique. PRESENTATION OF CASE A 40 yr. old female patient with FAP underwent surgery. Firstly, colon and the rectum mobilized completely, and then from the 10 cm. proximal to the ileo-caecal valve to the recto-sigmoid junction total colectomy was performed. Rectum was everted by a grasping forceps which was introduced through the anus and then resection was performed by a linear stapler just over the dentate line. A stapled J-shaped ileal reservoir construction followed by intraluminal stapler-facilitated ileoanal anastomosis. Follow up at six months anal sphincter function was found normal. DISCUSSION There is only surgical management option for FAP patients up to now. Total colectomy with IRA and restorative proctocolectomy with IPAA is surgical options for FAP patients that avoid the need for a permanent stoma. Anorectal eversion may be used in the surgical treatment of FAP, chronic ulcerative colitis and early stage distal rectal cancer patients. CONCLUSION J-pouch ileoanal anastomosis can safely be performed by rectal eversion and double stapler technique in FAP patients. PMID:25305601

  17. Enteropathogenic Escherichia coli inhibits ileal sodium-dependent bile acid transporter ASBT

    PubMed Central

    Annaba, Fadi; Sarwar, Zaheer; Gill, Ravinder K.; Ghosh, Amit; Saksena, Seema; Borthakur, Alip; Hecht, Gail A.; Dudeja, Pradeep K.

    2012-01-01

    Apical sodium-dependent bile acid transporter (ASBT) is responsible for the absorption of bile acids from the intestine. A decrease in ASBT function and expression has been implicated in diarrhea associated with intestinal inflammation. Whether infection with pathogenic microorganisms such as the enteropathogenic Escherichia coli (EPEC) affect ASBT activity is not known. EPEC is a food-borne enteric pathogen that translocates bacterial effector molecules via type three secretion system (TTSS) into host cells and is a major cause of infantile diarrhea. We investigated the effects of EPEC infection on ileal ASBT function utilizing human intestinal Caco2 cells and HEK-293 cells stably transfected with ASBT-V5 fusion protein (2BT cells). ASBT activity was significantly inhibited following 60 min infection with EPEC but not with nonpathogenic E. coli. Mutations in bacterial escN, espA, espB, and espD, the genes encoding for the elements of bacterial TTSS, ablated EPEC inhibitory effect on ASBT function. Furthermore, mutation in the bacterial BFP gene encoding for bundle-forming pili abrogated the inhibition of ASBT by EPEC, indicating the essential role for bacterial aggregation and the early attachment. The inhibition by EPEC was associated with a significant decrease in the Vmax of the transporter and a reduction in the level of ASBT on the plasma membrane. The inhibition of ASBT by EPEC was blocked in the presence of protein tyrosine phosphatase inhibitors. Our studies provide novel evidence for the alterations in the activity of ASBT by EPEC infection and suggest a possible effect for EPEC in influencing intestinal bile acid homeostasis. PMID:22403793

  18. Enteropathogenic Escherichia coli inhibits ileal sodium-dependent bile acid transporter ASBT.

    PubMed

    Annaba, Fadi; Sarwar, Zaheer; Gill, Ravinder K; Ghosh, Amit; Saksena, Seema; Borthakur, Alip; Hecht, Gail A; Dudeja, Pradeep K; Alrefai, Waddah A

    2012-05-15

    Apical sodium-dependent bile acid transporter (ASBT) is responsible for the absorption of bile acids from the intestine. A decrease in ASBT function and expression has been implicated in diarrhea associated with intestinal inflammation. Whether infection with pathogenic microorganisms such as the enteropathogenic Escherichia coli (EPEC) affect ASBT activity is not known. EPEC is a food-borne enteric pathogen that translocates bacterial effector molecules via type three secretion system (TTSS) into host cells and is a major cause of infantile diarrhea. We investigated the effects of EPEC infection on ileal ASBT function utilizing human intestinal Caco2 cells and HEK-293 cells stably transfected with ASBT-V5 fusion protein (2BT cells). ASBT activity was significantly inhibited following 60 min infection with EPEC but not with nonpathogenic E. coli. Mutations in bacterial escN, espA, espB, and espD, the genes encoding for the elements of bacterial TTSS, ablated EPEC inhibitory effect on ASBT function. Furthermore, mutation in the bacterial BFP gene encoding for bundle-forming pili abrogated the inhibition of ASBT by EPEC, indicating the essential role for bacterial aggregation and the early attachment. The inhibition by EPEC was associated with a significant decrease in the V(max) of the transporter and a reduction in the level of ASBT on the plasma membrane. The inhibition of ASBT by EPEC was blocked in the presence of protein tyrosine phosphatase inhibitors. Our studies provide novel evidence for the alterations in the activity of ASBT by EPEC infection and suggest a possible effect for EPEC in influencing intestinal bile acid homeostasis. PMID:22403793

  19. 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?

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

    PubMed

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

    2015-01-01

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

  1. [Inhibitory effects of glucose utilization by gymnema acids in the guinea-pig ileal longitudinal muscle].

    PubMed

    Shimizu, K; Abe, T; Nakajyo, S; Urakawa, N; Atsuchi, M; Yamashita, C

    1996-10-01

    Two substances identified as ((3 beta, 4 alpha, 16 beta, 21 beta, 22 alpha)-21-tigloxy-16, 22, 23, 28-tetrahydroxyolean-12-en-3-yl-beta D-glucopyranosiduronic acid) (GA1) and ((3 beta, 4 alpha, 16 beta, 21 beta, 22 alpha)-21-(2-methylbutyroxy)-16, 22, 23, 28-tetrahydroxyolean-12-en-3-yl-beta-D-glucopyranosiduronic acid) (GA2) identified among the gymnemic acids are triterpene glycosides extracted from Gymnema sylvestre leaves. We examined the effects of GA1 or GA2 on high K(+)-induced contraction in the guinea-pig longitudinal muscle. A sustained muscle contraction induced by hyperosmotically added 65.4 mM KCI (H-65K+) was suppressed by GA1 or GA2 (7.7 x 10(-5) M). Simultaneous measurements of reduced pyridine nucleotide (PNred) or oxidized flavin protein (FPox) by the fluorescence technique and of contractile force revealed that GA1 and GA2 reduced the increase of PNred fluorescence and contractile force induced by H-65K+, whereas FPox fluorescence induced by it further increased. Reduced muscle contraction induced by GA1 or GA2 was restored by 5.5 mM pyruvate. Simultaneous measurements of intracellular Ca2+ [Ca2+]1 level and contractile force indicated that [Ca2+]1 level, which increased by H-65K+, hardly changed with GA1 and GA2. In summary, both GA1 and GA2, which are among the gymnemic acids, suppressed high K(+)-induced contraction in the guinea-pig ileal longitudinal muscle. The difference between these two gymnemic acids was not significant. The inhibitory effect of GA1 and GA2 on smooth muscle were assumed to be a result of inhibiting glucose uptake, which is an energy source of the muscle, whereas the inhibitory mechanisms were probably not mediated by Ca2+. PMID:8985922

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

    PubMed

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

    2014-07-25

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

  3. Modulation of cadmium-induced oxidative stress in Ceratophyllum demersum by zinc involves ascorbate-glutathione cycle and glutathione metabolism.

    PubMed

    Aravind, Parameswaran; Prasad, Majeti Narasimha Vara

    2005-02-01

    To understand the interaction between Zn, an essential micronutrient and Cd, a non-essential element, Cd-10 microM and Zn supplemented (10, 50, 100, and 200 microM) Cd 10 microM treated Ceratophyllum demersum L. (Coontail), a free floating freshwater macrophyte was chosen for the study. Cadmium at 10 microM concentration decreased thiol content, enhanced oxidation of ascorbate (AsA) and glutathione (GSH) to dehydroascorbate (DHA) and glutathione disulfide (GSSG), respectively, a clear indication of oxidative stress. Zinc supplementation to Cd (10 microM) treated plants effectively restored thiols, inhibited oxidation of AsA and GSH maintaining the redox molecules in reduced form. Cd-10 microM slightly induced ascorbate peroxidase (APX, E.C. 1.11.1.11) but inhibited monodehydroascorbate reductase (MDHAR, E.C. 1.6.5.4), dehydroascorbate reductase (DHAR, E.C. 1.8.5.1) and glutathione reductase (GR, E.C. 1.6.4.2), enzymes of ascorbate-glutathione cycle (AGC). Zn supplementation restored and enhanced the functional activity of all the AGC enzymes (APX, MDHAR, DHAR and GR). Gamma-glutamylcysteine synthetase (gamma-GCS, E.C. 6.3.2.2) was not affected by Cd as well as Zn, but Zn supplements increased glutathione-S-transferase (GST, E.C. 2.5.1.18) activity to a greater extent than Cd and simultaneously restored glutathione peroxidase (GSH-PX, E.C. 1.11.1.9) activity impaired by Cd toxicity. Zn-alone treatments did not change above investigated parameters. These results clearly indicate the protective role of Zn in modulating the redox status of the plant system through the antioxidant pathway AGC and GSH metabolic enzymes for combating Cd induced oxidative stress. PMID:15820657

  4. Role of Ascorbate Peroxidase and Glutathione Reductase in Ascorbate–Glutathione Cycle and Stress Tolerance in Plants

    Microsoft Academic Search

    Cai-Hong Pang; Bao-Shan Wang

    \\u000a Ascorbate–glutathione (AsA–GSH) cycle is an important component of the scavenging system for reactive oxygen compounds in\\u000a plants. The member of this pathway involves the antioxidants: AsA, GSH and the antioxidatnt enzymes such as ascorbate peroxidase\\u000a (APX), monodehydroascorbate reductase (MDAsAR), dehydroascorbate reductase (DAsAR) and glutathione reductase (GR). APX and\\u000a GR are the key enzymes of the AsA–GSH cycle. APX utilizes AsA

  5. Interactions of alpha beta-unsaturated carbonyl compounds with the glutathione-related biotransformation system

    Microsoft Academic Search

    Iersel van M. L. P. S

    1998-01-01

    Introduction<\\/strong>Modulation of glutathione-related biotransformation steps may play a role in important phenomena as anticarcinogenicity and multidrug resistance. Glutathione-related biotransformation comprises three main aspects i.e. glutathione, the glutathione S-transferases and the multidrug resistance associated protein pump. In Figure 6.1 is shown how the levels and relative activities of these three entities interact.The research presented in this thesis focused on the effects

  6. The gut mucosal immune response to Toxoplasma gondii.

    PubMed

    Cohen, S B; Denkers, E Y

    2015-03-01

    As an orally acquired pathogen, the immune response to Toxoplasma gondii unfolds in the small intestinal mucosa. There, an array of regulatory and effector immune cells are elicited to combat the parasite through secretion of inflammatory mediators, normally resulting in host protection and pathogen control. Recent studies largely in mice have found that a productive immune response requires the combined recognition of parasite- and commensal-derived antigens by mucosal leucocytes. However, despite the fine-tuned regulatory mechanisms in place to prevent immunopathology, dysregulated responses can occur in genetically susceptible subjects, leading to lethal pro-inflammatory-mediated intestinal damage. Here, we describe the current understanding of the inflammatory players involved in orchestrating immunity or immunopathology in the intestine during the mucosal response to Toxoplasma infection. PMID:25418610

  7. Mucosal prelamination of a radial forearm flap for intraoral reconstruction.

    PubMed

    Rath, T; Millesi, W; Millesi-Schobel, G; Lang, S

    1997-10-01

    For reconstruction of intraoral soft-tissue defects after radical resection of squamous-cell carcinomas, the microvascular jejunal patch has been a reconstructive graft option of first choice. in addition to other advantages, these jejunal grafts are able to produce mucus. In cases in which the use of jejunal grafts is contraindicated, the fasciocutaneous radial forearm flap has enlarged the spectrum of reconstructive options. A disadvantage is that mucus production will be absent, because mucosal and lining reconstruction is performed with tissue lacking mucus-providing qualities. The authors successfully prelaminated a distal radial forearm flap with buccal mucosa in five patients. Mucosal prelamination of the distal radial forearm flap enables a physiologic reconstruction with resultant mucus production, in combination with the provision of thin, pliable, and resistant flaps. The technique lowers donor-site morbidity because of the preservation of skin and subcutaneous tissue. Reconstruction with fasciomucosal, osteomyomucosal, and myomucosal flaps by this method seems feasible. PMID:9353703

  8. TL and CD8??: Enigmatic Partners in Mucosal Immunity

    PubMed Central

    Olivares-Villagómez, Danyvid; Van Kaer, Luc

    2010-01-01

    The intestinal mucosa represents a large surface area that is in contact with an immense antigenic load. The immune system associated with the intestinal mucosa needs to distinguish between innocuous food antigens, commensal microorganisms, and pathogenic microorganisms, without triggering an exaggerated immune response that may lead to excessive inflammation and/or development of inflammatory bowel disease. The thymus leukemia (TL) antigen and CD8?? are interacting surface molecules that are expressed at the frontline of the mucosal immune system: TL is expressed in intestinal epithelial cells (IEC) whereas CD8?? is expressed in lymphocytes, known as intraepithelial lymphocytes, that reside in between the IEC. In this review we discuss the significance of the interaction between TL and CD8?? in mucosal immunity during health and disease. PMID:20850477

  9. Development of Mucosal Vaccines Based on Lactic Acid Bacteria

    NASA Astrophysics Data System (ADS)

    Bermúdez-Humarán, Luis G.; Innocentin, Silvia; Lefèvre, Francois; Chatel, Jean-Marc; Langella, Philippe

    Today, sufficient data are available to support the use of lactic acid bacteria (LAB), notably lactococci and lactobacilli, as delivery vehicles for the development of new mucosal vaccines. These non-pathogenic Gram-positive bacteria have been safely consumed by humans for centuries in fermented foods. They thus constitute an attractive alternative to the attenuated pathogens (most popular live vectors actually studied) which could recover their pathogenic potential and are thus not totally safe for use in humans. This chapter reviews the current research and advances in the use of LAB as live delivery vectors of proteins of interest for the development of new safe mucosal vaccines. The use of LAB as DNA vaccine vehicles to deliver DNA directly to antigen-presenting cells of the immune system is also discussed.

  10. Mucosal Immunity in the Female Genital Tract, HIV/AIDS

    PubMed Central

    Reis Machado, Juliana; da Silva, Marcos Vinícius; Cavellani, Camila Lourencini; Antônia dos Reis, Marlene; Monteiro, Maria Luiza Gonçalves dos Reis; Teixeira, Vicente de Paula Antunes; Rosa Miranda Corrêa, Rosana

    2014-01-01

    Mucosal immunity consists of innate and adaptive immune responses which can be influenced by systemic immunity. Despite having been the subject of intensive studies, it is not fully elucidated what exactly occurs after HIV contact with the female genital tract mucosa. The sexual route is the main route of HIV transmission, with an increased risk of infection in women compared to men. Several characteristics of the female genital tract make it suitable for inoculation, establishment of infection, and systemic spread of the virus, which causes local changes that may favor the development of infections by other pathogens, often called sexually transmitted diseases (STDs). The relationship of these STDs with HIV infection has been widely studied. Here we review the characteristics of mucosal immunity of the female genital tract, its alterations due to HIV/AIDS, and the characteristics of coinfections between HIV/AIDS and the most prevalent STDs. PMID:25313360

  11. The gut mucosal immune system in the neonatal period.

    PubMed

    Battersby, Anna J; Gibbons, Deena L

    2013-08-01

    Invasive sepsis in the newborn period is a major cause of childhood morbidity and mortality worldwide. The infant immune system undoubtedly differs intrinsically from the mature adult immune system. Current understanding is that the newborn infant immune system displays a range of competencies and is developing rather than deficient. The infant gut mucosal immune system is complex and displays a plethora of phenotypic and functional irregularities that may be clinically important. Various factors affect and modulate the infant gut mucosal immune system: components of the intestinal barrier, the infant gut microbiome, nutrition and the maternal-infant hybrid immune system. Elucidation of the phenotypic distribution of immune cells, their functional significance and the mucosa-specific pathways used by these cells is essential to the future of research in the field of infant immunology. PMID:23682966

  12. Type I interferons in regulation of mucosal immunity.

    PubMed

    Mangan, Niamh E; Fung, Ka Yee

    2012-05-01

    The mucosal system is the first line of defense against many pathogens. It is continuously exposed to dietary and microbial antigens, and thus the host must maintain a homeostatic environment between commensal microbiota and pathogenic infections. Following infections and inflammatory events, a rapid innate immune response is evoked to dampen the inflammatory processes. Type I interferons, a family of pleiotropic cytokines and major products of the innate immune response, have a key role in these early immune events at the mucosa, as reviewed here. With the emergence of new discoveries of immune cell types in mucosal tissues and their reactions to commensal and pathogenic organisms, we also review the opportunities for exciting research in this field. PMID:22430250

  13. METAL-INDUCED INHIBITION OF GLUTATHIONE S-TRANSFERASES

    EPA Science Inventory

    The glutathione S-transferases comprise a group of multi-functional enzymes involved in the biotransformation/detoxication of a broad spectrum of hydrophobic compounds bearing an electrophilic center. The enzymes facilitate the nucleophilic attack of the -SH group of reduced glut...

  14. Pulmonary Glutathione Levels in Acute Episodes of Farmer's Lung

    Microsoft Academic Search

    JÜRGEN BEHR; BARBARA DEGENKOLB; THOMAS BEINERT; FRITZ KROMBACH; CLAUS VOGELMEIER

    2000-01-01

    Acute episodes of farmer's lung (FL) are associated with activation and migration of neutrophils into the lungs, causing oxidative stress. We conducted a study to evaluate the effect of episodes of FL on antioxidant defense of the lung by glutathione (GSH). A to- tal of 15 patients with symptomatic FL (one female and 14 males, age 42 6 1 yr

  15. Blood Glutathione Disulfide: In Vivo Factor or in Vitro Artifact?

    Microsoft Academic Search

    Ranieri Rossi; Aldo Milzani; Isabella Dalle-Donne; Daniela Giustarini; Lorenzo Lusini; Roberto Colombo; Paolo Di Simplicio

    2002-01-01

    Background: The reported mean concentration of glu- tathione disulfide (GSSG) in human blood\\/erythrocytes varies widely (1 to >500 mol\\/L), as does that of reduced glutathione (GSH) to a lesser extent. We have identified and investigated possible pitfalls in measurement of both GSH and GSSG. Methods: We measured GSH and GSSG using a spec- trophotometer with a modification of the GSH

  16. The evolution of glutathione metabolism in phototrophic microorganisms

    Microsoft Academic Search

    Robert C. Fahey; Ralph M. Buschbacher; Gerald L. Newton

    1987-01-01

    Summary Of the many roles ascribed to glutathione (GSH) the one most clearly established is its role in the protection of higher eucaryotes against oxygen toxicity through destruction of thiol-reactive oxygen byproducts. If this is the primary function of GSH then GSH metabolism should have evolved during or after the evolution of oxygenic photosynthesis. That many bacteria do not produce

  17. 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 ...

  18. Cystamine induces AIF-mediated apoptosis through glutathione depletion.

    PubMed

    Cho, Sung-Yup; Lee, Jin-Haeng; Ju, Mi-Kyeong; Jeong, Eui Man; Kim, Hyo-Jun; Lim, Jisun; Lee, Seungun; Cho, Nam-Hyuk; Park, Hyun Ho; Choi, Kihang; Jeon, Ju-Hong; Kim, In-Gyu

    2015-03-01

    Cystamine and its reduced form cysteamine showed protective effects in various models of neurodegenerative disease, including Huntington's disease and Parkinson's disease. Other lines of evidence demonstrated the cytotoxic effect of cysteamine on duodenal mucosa leading to ulcer development. However, the mechanism for cystamine cytotoxicity remains poorly understood. Here, we report a new pathway in which cystamine induces apoptosis by targeting apoptosis-inducing factor (AIF). By screening of various cell lines, we observed that cystamine and cysteamine induce cell death in a cell type-specific manner. Comparison between cystamine-sensitive and cystamine-resistant cell lines revealed that cystamine cytotoxicity is not associated with unfolded protein response, reactive oxygen species generation and transglutaminase or caspase activity; rather, it is associated with the ability of cystamine to trigger AIF nuclear translocation. In cystamine-sensitive cells, cystamine suppresses the levels of intracellular glutathione by inhibiting ?-glutamylcysteine synthetase expression that triggers AIF translocation. Conversely, glutathione supplementation completely prevents cystamine-induced AIF translocation and apoptosis. In rats, cysteamine administration induces glutathione depletion and AIF translocation leading to apoptosis of duodenal epithelium. These results indicate that AIF translocation through glutathione depletion is the molecular mechanism of cystamine toxicity, and provide important implications for cystamine in the neurodegenerative disease therapeutics as well as in the regulation of AIF-mediated cell death. PMID:25549939

  19. 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...

  20. Characterization of Anopheles dirus Glutathione Transferase Epsilon 4

    Microsoft Academic Search

    Gulsiri Charoensilp; Ardcharaporn Vararattanavech; Posri Leelapat; La-aied Prapanthadara; Albert J. Ketterman

    2006-01-01

    The coding sequences of a wild type glutathione transferase (GST) Epsilon 4 and three isoenzymes were obtained by RT-PCR from a Thai malaria mosquito, Anopheles dirus. After confirmation by sequencing, the RT-PCR products were subcloned into an expression vector and proteins were expressed, purified, and biochemically characterized to study the function of these enzymes and for comparison with two orthologs

  1. A simple assay for glutathione in whole blood

    PubMed Central

    Hakuna, Lovemore; Doughan, Brandon; Escobedo, Jorge O.

    2015-01-01

    A method for detecting glutathione selectively in whole blood deposited on filter paper is described. GSH is fractionated from proteins, hemoglobin and other potentially interfering components and determined using a resorufin-acrylate fluorescent probe. The relative standard deviation is lower than 5% (n = 5). Recoveries of GSH from whole blood are between 94% and 108.6%. PMID:25913023

  2. Reaction Mechanism and Regulation of Mammalian Thioredoxin\\/Glutathione Reductase †

    Microsoft Academic Search

    Qi-An Sun; Dan Su; Sergey V. Novoselov; Bradley A. Carlson; Dolph L. Hatfield; Vadim N. Gladyshev

    2005-01-01

    Thioredoxin\\/glutathione reductase (TGR) is a recently discovered member of the selenoprotein thioredoxin reductase family in mammals. In contrast to two other mammalian thioredoxin reductases, it contains an N-terminal glutaredoxin domain and exhibits a wide spectrum of enzyme activities. To elucidate the reaction mechanism and regulation of TGR, we prepared a recombinant mouse TGR in the selenoprotein form as well as

  3. Spontaneous Mucosal Lymphocyte Cytokine Profiles in Children with Autism and Gastrointestinal Symptoms: Mucosal Immune Activation and Reduced Counter Regulatory Interleukin10

    Microsoft Academic Search

    PAUL ASHWOOD; ANDREW ANTHONY; FRANCO TORRENTE; ANDREW J. WAKEFIELD

    2004-01-01

    A lymphocytic enterocolitis has been reported in a cohort of children with autistic spectrum disorder (ASD) and gastrointestinal (GI) symptoms. This study tested the hypothesis that dysregulated intestinal mucosal immunity with enhanced pro-inflammatory cytokine production is present in these ASD children. Comparison was made with developmentally normal children with, and without, mucosal inflammation. Duodenal and colonic biopsies were obtained from

  4. Polymer nanotechnology based approaches in mucosal vaccine delivery: challenges and opportunities.

    PubMed

    Sharma, Rajeev; Agrawal, Udita; Mody, Nishi; Vyas, Suresh P

    2015-01-01

    Mucosal sites serve as the main portal for the entry of pathogens and thus immunization through mucosal routes can greatly improve the immunity. Researchers are continuously exploring the vaccination strategies to engender protective mucosal immune responses. Unearthing of mucosal adjuvants, that are safe and effective, is enhancing the magnitude and quality of the protective immune response. Use of nanotechnology based polymeric nanocarrier systems which encapsulate vaccine components for protection of sensitive payload, incorporate mucosal adjuvants to maximize the immune responses and target the mucosal immune system is a key strategy to improve the effectiveness of mucosal vaccines. These advances promise to accelerate the development and testing of new mucosal vaccines against many human diseases. This review focuses on the need for the development of nanocarrier based mucosal vaccines with emphases on the polymeric nanoparticles, their clinical status and future perspectives. This review focuses on the need and new insights for the development of nanoarchitecture governed mucosal vaccination with emphases on the various polymeric nanoparticles, their clinical status and future perspectives. PMID:25499178

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

    PubMed Central

    2014-01-01

    Background The antimetabolite chemotherapy 5-Fluorouracil is one of the most commonly prescribed drugs in clinical cancer treatment. Although this drug is not specific for cancer cells and also acts on healthy cells, it can cause mucositis, a common collateral effect. Dysbiosis has also been described in 5-fluorouracil-induced mucositis and is likely to contribute to the overall development of mucositis. In light of this theory, the use of probiotics could be a helpful strategy to alleviate mucositis. So the aim of this study was evaluate the impact of the probiotic Saccharomyces boulardii in a model of mucositis. Results After induced of mucositis, mice from the Mucositis groups showed a decrease in food consumption (p??0.05). Mucositis induced an increase in intestinal permeability and intestinal inflammation (p?mucosal lesions, intestinal permeability and sIgA secretion (p?>?0.05) in mice pretreated with S. boulardii. Conclusions S. boulardii was not able to prevent the effects of experimental mucositis induced by 5- Fluorouracil. PMID:24721659

  6. Risk analysis, diagnosis and management of gastrointestinal mucositis in pediatric cancer patients.

    PubMed

    Kuiken, Nicoline S S; Rings, Edmond H H M; Tissing, Wim J E

    2015-04-01

    Mucositis is a complex inflammatory reaction of the mucous membranes of the alimentary tract upon chemotherapy and radiotherapy treatment in oncology patients. Mucositis can be subdivided in oral and gastrointestinal mucositis (GI mucositis). The damage to the gastrointestinal tract compromises the intestinal function and thereby the nutritional status and the quality of life, and eventually affects survival. The literature on GI mucositis focuses mainly on adults. This review focuses on data available on GI mucositis in pediatric cancer patients. An evaluation of the clinical presentation and consequences of GI mucositis in children is outlined. The review summarizes key issues for clinicians with respect to risk analysis for developing mucositis and the diagnosis of this condition in children. Information on these issues is obtained from clinical trials in children and adults, and from animal models. Diagnostic tools and assessment of severity of GI mucositis in children is elaborated on. Furthermore, the clinical management of the symptoms and consequences of GI mucositis in children, with specific focus on nutritional support, are discussed. PMID:25560731

  7. A clinicopathological and immunohistochemical analysis of primary oral mucosal melanoma

    Microsoft Academic Search

    A. W. Barrett; J. H. Bennett; P. M. Speight

    1995-01-01

    Nine cases of primary oral mucosal melanoma in Caucasian patients were reviewed and the tumours analysed for expression of S100, HMB45, NKI\\/C3, HLA-DR, PCNA, cytokeratin and von Willebrand factor. The clinical, histopathological and immunohistochemical features were quite distinctive and our findings support previous suggestions that oral melanoma should be classified as a separate entity rather than as a sub-type of

  8. Smad3 knockout mice exhibit impaired intestinal mucosal healing

    Microsoft Academic Search

    Cheri R Owen; Lisi Yuan; Marc D Basson

    2008-01-01

    Altered transforming growth factor-? (TGF?) expression may contribute to inflammatory bowel disease and modulate epithelial cell restitution. Interference with TGF?-mediated signaling inhibits excisional skin wound healing, but accelerates healing of incisional cutaneous wounds and wounds in some other tissues. Therefore, we sought to clarify the potential role of Smad3-dependent TGF? signaling in intestinal mucosal healing in Smad3 null mice. Jejunal

  9. Eosinophilic gastroenteritis: A problem of the mucosal immune system?

    Microsoft Academic Search

    Mi-Na Kweon; Hiroshi Kiyono

    2003-01-01

    The gastrointestinal immune system is a major component of the mucosal barrier, which provides an appropriate immunologic\\u000a homeostasis between host and numerous foreign antigens, including microbial and dietary antigens. However, under certain pathological\\u000a circumstances created by disturbance of the immunologic balance, allergic responses associated with the gastrointestinal tract\\u000a can be triggered by abnormal immune responses against selected food protein antigens.

  10. Feline gastrointestinal lymphoma: mucosal architecture, immunophenotype, and molecular clonality.

    PubMed

    Moore, P F; Rodriguez-Bertos, A; Kass, P H

    2012-07-01

    Gastrointestinal lymphomas were identified in 120 cats between 1995 and 2006. Lymphomas were classified according to the World Health Organization (WHO) scheme. Cats with mucosal T-cell lymphoma (n = 84) predominated and had a median survival of 29 months. Mucosal T-cell lymphoma matched WHO enteropathy-associated T-cell lymphoma (EATCL) type II. Epitheliotropic T-cell infiltrates were present in 62% of cats and occurred as clusters or diffuse infiltrates of small to intermediate-sized T cells in villous and/or crypt epithelium. Similar lymphocytes infiltrated the lamina propria in distinctive patterns. Cats with transmural T-cell lymphoma (n = 19) had a median survival of 1.5 months. Transmural T-cell lymphoma matched WHO EATCL type I. Epitheliotropic T-cell infiltrates were present in 58% of cats. Large lymphocytes (n = 11), mostly with cytoplasmic granules (LGL-granzyme B+) (n = 9) predominated. Transmural extension across the muscularis propria characterized the lesion. Both mucosal and transmural T-cell lymphomas were largely confined to the small intestine, and molecular clonality analysis revealed clonal or oligoclonal rearrangements of T-cell receptor-? in 90% of cats. Cats with B-cell lymphoma (n = 19) had a median survival of 3.5 months. B-cell lymphomas occurred as transmural lesions in stomach, jejunum, and ileo-cecal-colic junction. The majority were diffuse, large B-cell lymphomas of centroblastic type. In conclusion, T-cell lymphomas characterized by distinctive mucosal architecture, CD3 expression, and clonal expansion predominated in the feline gastrointestinal tract. PMID:21505197

  11. What interactions drive the salivary mucosal pellicle formation?

    PubMed Central

    Gibbins, Hannah L.; Yakubov, Gleb E.; Proctor, Gordon B.; Wilson, Stephen; Carpenter, Guy H.

    2014-01-01

    The bound salivary pellicle is essential for protection of both the enamel and mucosa in the oral cavity. The enamel pellicle formation is well characterised, however the mucosal pellicle proteins have only recently been clarified and what drives their formation is still unclear. The aim of this study was to examine the salivary pellicle on particles with different surface properties (hydrophobic or hydrophilic with a positive or negative charge), to determine a suitable model to mimic the mucosal pellicle. A secondary aim was to use the model to test how transglutaminase may alter pellicle formation. Particles were incubated with resting whole mouth saliva, parotid saliva and submandibular/sublingual saliva. Following incubation and two PBS and water washes bound salivary proteins were eluted with two concentrations of SDS, which were later analysed using SDS-PAGE and Western blotting. Experiments were repeated with purified transglutaminase to determine how this epithelial-derived enzyme may alter the bound pellicle. Protein pellicles varied according to the starting salivary composition and the particle chemistry. Amylase, the single most abundant protein in saliva, did not bind to any particle indicating specific protein binding. Most proteins bound through hydrophobic interactions and a few according to their charges. The hydrophobic surface most closely matched the known salivary mucosal pellicle by containing mucins, cystatin and statherin but an absence of amylase and proline-rich proteins. This surface was further used to examine the effect of added transglutaminase. At the concentrations used only statherin showed any evidence of crosslinking with itself or another saliva protein. In conclusion, the formation of the salivary mucosal pellicle is probably mediated, at least in part, by hydrophobic interactions to the epithelial cell surface. PMID:24921197

  12. Intestinal epithelial cells and their role in innate mucosal immunity

    Microsoft Academic Search

    A. L. Maldonado-Contreras; Beth A. McCormick

    2011-01-01

    The mucosal surfaces of the respiratory, gastrointestinal and urogenital tracts are covered by a layer of epithelial cells\\u000a that are responsible for sensing and promoting a host immune response in order to establish the limits not only for commensal\\u000a microorganisms but also for foreign organisms or particles. This is a remarkable task as the human body represents a composite\\u000a of

  13. Th17 Cytokines and the Gut Mucosal Barrier

    Microsoft Academic Search

    Christoph Blaschitz; Manuela Raffatellu

    2010-01-01

    Local immune responses serve to contain infections by pathogens to the gut while preventing pathogen dissemination to systemic\\u000a sites. Several subsets of T cells in the gut (T-helper 17 cells, ?? T cells, natural killer (NK), and NK-T cells) contribute\\u000a to the mucosal response to pathogens by secreting a subset of cytokines including interleukin (IL)-17A, IL-17F, IL-22, and\\u000a IL-26. These

  14. Survey of Mucositis Management in Children with Cancer

    Microsoft Academic Search

    Kirk Lalwani; Helen Turner

    Results: 53 replies were received (50.4%), of which 34 (64.2%) were from children s hospitals {private, 11 (20.8%); university or affiliated, 23 (43.4%)}. 18 (34%) were adult hospitals with a pediatric oncology unit. Children received a dental evaluation prior to chemotherapy in 36 (67.9) hospitals. Patients or parents were counseled about oral hygiene\\/mouth-care, diet, and treatment options for mucositis in

  15. Psittacid herpesviruses associated with mucosal papillomas in neotropical parrots.

    PubMed

    Styles, Darrel K; Tomaszewski, Elizabeth K; Jaeger, Laurie A; Phalen, David N

    2004-07-20

    Mucosal papillomas are relatively common lesions in several species of captive neotropical parrots. They cause considerable morbidity and in some cases, result in mortality. Previous efforts to identify papillomavirus DNA and proteins in these lesions have been largely unsuccessful. In contrast, increasing evidence suggests that mucosal papillomas may contain psittacid herpesviruses (PsHVs). In this study, 41 papillomas from 30 neotropical parrots were examined by PCR with PsHV-specific primers. All 41 papillomas were found to contain PsHV DNA. This 100% prevalence of PsHV infection in the papilloma population was found to be significantly higher than PsHV infection prevalence observed in other surveys of captive parrots. PsHV genotypes 1, 2, and 3, but not 4 were found in these lesions. Psittacus erithacus papillomavirus DNA and finch papillomavirus DNA were not found in the papillomas. A papilloma from a hyacinth macaw (Anodorhynchus hyacinthinus) was found to contain cells that had immunoreactivity to antiserum made to the common antigenic region of human papillomavirus (HPV) L1 major capsid protein. However, four other mucosal papillomas were negative for this immunoreactivity, and negative control tissues from a parrot embryo showed a similar staining pattern to that seen in the cloaca papilloma of the hyacinth macaw, strongly suggesting that the staining seen in hyacinth macaw papilloma was nonspecific. Based on these findings, it was concluded that specific genotypes of PsHV play a direct role in the development of mucosal papillomas of neotropical parrots and there is no evidence to suggest the concurrent presence of a papillomavirus in these lesions. PMID:15231383

  16. Rotavirus Virus-Like Particles Administered Mucosally Induce Protective Immunity

    Microsoft Academic Search

    CHRISTINE M. O'NEAL; SUE E. CRAWFORD; MARY K. ESTES; MARGARET E. CONNER

    1997-01-01

    We have evaluated the immunogenicity and protective efficacy of rotavirus subunit vaccines administered by mucosal routes. Virus-like particles (VLPs) produced by self-assembly of individual rotavirus structural proteins coexpressed by baculovirus recombinants in insect cells were the subunit vaccine tested. We first compared the immunogenicities and protective efficacies of VLPs containing VP2 and VP6 (2\\/6-VLPs) and G3 2\\/6\\/7-VLPs mixed with cholera

  17. Ex vivo development of a composite human oral mucosal equivalent

    Microsoft Academic Search

    Kenji Izumi; Gyula Takacs; Hiroto Terashi; Stephen E Feinberg

    1999-01-01

    Purpose: The aim of this study was the ex vivo development of a composite oral mucosal equivalent composed of a continuous stratified layer of human oral keratinocytes grown on a cadaveric human dermal matrix in a defined medium without a feeder layer.Materials and Methods: Enzymatically dissociated human oral keratinocytes from keratinized oral mucosa were cultured, submerged in a serum-free, low-calcium

  18. Oral mucosal blood flow in patients with burning mouth syndrome

    Microsoft Academic Search

    S. M Heckmann; J. G Heckmann; M. J HiIz; M Popp; H Marthol; B Neundörfer; T Hummel

    2001-01-01

    The pathophysiology of burning mouth syndrome (BMS) is largely unknown. Thus, the aim was to study oral mucosal blood flow in BMS-patients using laser Doppler flowmetry (LDF). Thirteen BMS patients (11 female, two male; mean age±SD 64.3±7.9 years, mean disease duration 18.9±6.2 months) and 13 healthy non-smoking controls matched for age and gender (11 female, two male; mean age 64.7±8.1

  19. Involvement of glutathione and glutathione metabolizing enzymes in human colorectal cancer cell lines and tissues.

    PubMed

    Kim, Areum Daseul; Zhang, Rui; Han, Xia; Kang, Kyoung Ah; Piao, Mei Jing; Maeng, Young Hee; Chang, Weon Young; Hyun, Jin Won

    2015-09-01

    Reduced glutathione (GSH) is an abundant tripeptide present in the majority of cell types. GSH is highly reactive and is often conjugated to other molecules, via its sulfhydryl moiety. GSH is synthesized from glutamic acid, cysteine, and glycine via two sequential ATP?consuming steps, which are catalyzed by glutamate cysteine ligase (GCL) and GSH synthetase (GSS). However, the role of GSH in cancer remains to be elucidated. The present study aimed to determine the levels of GSH and GSH synthetic enzymes in human colorectal cancer. The mRNA and protein expression levels of GSH, the catalytic subunit of GCL (GCLC) and GSS were significantly higher in the following five colon cancer cell lines: Caco?2, SNU?407, SNU?1033, HCT?116, and HT?29, as compared with the normal colon cell line, FHC. Similarly, in 9 out of 15 patients with colon cancer, GSH expression levels were higher in tumor tissue, as compared with adjacent normal tissue. In addition, the protein expression levels of GCLC and GSS were higher in the tumor tissue of 8 out of 15, and 10 out of 15 patients with colon cancer respectively, as compared with adjacent normal tissue. Immunohistochemical analyses confirmed that GCLC and GSS were expressed at higher levels in colon cancer tissue, as compared with normal mucosa. Since GSH and GSH metabolizing enzymes are present at elevated levels in colonic tumors, they may serve as clinically useful biomarkers of colon cancer, and/or targets for anti-colon cancer drugs. PMID:26059756

  20. Properties of glutathione peroxidase from the hepatopancreas of freshwater prawn Macrobrachium malcolmsonii

    Microsoft Academic Search

    S Arun; P Krishnamoorthy; P Subramanian

    1999-01-01

    Oxidative stress stimulates production of hydrogen peroxide and organic hydroperoxides which are involved in lipid peroxidation and oxidative damage to protein. Glutathione peroxidase protects against oxidative stress. Quantitative data on glutathione peroxidase of crustaceans are very limited and so this study was performed to determine the assay condition of glutathione peroxidase in crustaceans. Particularly, some properties of hepatic selenium dependent

  1. Glutathione depletion causes cytochrome c release even in the absence of cell commitment to apoptosis

    Microsoft Academic Search

    L. GHIBELLI; S. COPPOLA; C. FANELLI; G. ROTILIO; P. CIVITAREALE; A. I. SCOVASSI; M. R. CIRIOLO

    We demonstrate here that the release of mature cytochrome c from mitochondria is a cellular response to the depletion of glutathione, the main intracellular antioxidant, independently from the destiny of the cells, i.e., apoptosis or survival. On the one hand, cytosolic cytochrome c was detected in cells where the inhibition of glutathione synthesis led to glutathione depletion without impairing viability

  2. GLUTATHIONE METABOLISM IN RATS EXPOSED TO HIGH FLUORIDE WATER AND EFFECT OF SPIRULINA TREATMENT

    Microsoft Academic Search

    Toshi Kaushik; Radhey Shyam; Praveen Vats; Shoba Suri; Mml Kumria; Pc Sharma; Som Nath Singh

    2001-01-01

    mins and minerals, for study of protective effects. After 15 days of exposure reduced and oxidised glutathione (GSH and GSSG), lipid peroxidation and enzymes, i.e. glutathione reductase (GR), glutathione peroxidase (GPx), gluta- thione S-transferase (GST), and ? ? ? ?-glutamyl transpeptidase (? ? ? ?-GT) activities were measured in blood\\/erythrocytes and liver. There was a significant rise in blood GSSG

  3. Oral complications of cancer therapies. Management of mucositis during therapy

    SciTech Connect

    Miaskowski, C. (Univ. of California, San Francisco (USA))

    1990-01-01

    This paper reviews the purposes of an oral care protocol, the major components of an oral care regimen, and oral care protocols and studies done to date. Many questions remain in the area of optimal oral care for the patient experiencing mucositis as a sequela of cancer treatment. Research is needed on types and use of mouth rinses, effective, harmless, and pleasant lip lubricants, appropriate analgesic and anti-inflammatory combinations, and the effectiveness of a variety of devices for oral cleansing, to name a few areas. As outpatient oncology services grow, oral care protocols must be developed to meet the needs of ambulatory patient populations. Oral care regimens must be safe, easy to use, and economical as well as effective to ensure patient and staff compliance. Research on the management of mucositis must be conducted in both inpatient and outpatient settings. Finally, in order to obtain sufficient sample sizes and optimize data collection, these studies will need to be conducted by multidisciplinary teams (including dentists, oncologists, radiation therapists, and nurses) across multiple sites. Not until large-scale clinical trials are done on the treatment of mucositis will we be able to optimize the therapeutic regimen for the patient. 43 references.

  4. JAM-related proteins in mucosal homeostasis and inflammation.

    PubMed

    Luissint, Anny-Claude; Nusrat, Asma; Parkos, Charles A

    2014-03-01

    Mucosal surfaces are lined by epithelial cells that form a physical barrier protecting the body against external noxious substances and pathogens. At a molecular level, the mucosal barrier is regulated by tight junctions (TJs) that seal the paracellular space between adjacent epithelial cells. Transmembrane proteins within TJs include junctional adhesion molecules (JAMs) that belong to the cortical thymocyte marker for Xenopus family of proteins. JAM family encompasses three classical members (JAM-A, JAM-B, and JAM-C) and related molecules including JAM4, JAM-like protein, Coxsackie and adenovirus receptor (CAR), CAR-like membrane protein and endothelial cell-selective adhesion molecule. JAMs have multiple functions that include regulation of endothelial and epithelial paracellular permeability, leukocyte recruitment during inflammation, angiogenesis, cell migration, and proliferation. In this review, we summarize the current knowledge regarding the roles of the JAM family members in the regulation of mucosal homeostasis and leukocyte trafficking with a particular emphasis on barrier function and its perturbation during pathological inflammation. PMID:24667924

  5. Cancer patients with oral mucositis: challenges for nursing care1

    PubMed Central

    Araújo, Sarah Nilkece Mesquita; Luz, Maria Helena Barros Araújo; da Silva, Grazielle Roberta Freitas; Andrade, Elaine Maria Leite Rangel; Nunes, Lívio César Cunha; Moura, Renata Oliveira

    2015-01-01

    OBJECTIVE: to analyze nursing care provided to cancer patients with oral mucositis based on the Nursing Process (NP). METHOD: this exploratory, descriptive, cross-sectional and quantitative study was conducted with 213 patients undergoing chemotherapy and/or radiotherapy in two cancer facilities: one philanthropic and one private service. RESULTS: the participants were mainly female, aged 45.8 years old on average, with up to 11 years of schooling and income of up to one times the minimum wage. Severe mucositis was related to chemotherapy associated with radiotherapy. Only 25.3% of the patients reported having received guidance from nurses during their treatment concerning self-care. The perceptions of patients regarding quality of care did not significantly differ between the private and public facilities. The basic human needs mainly affected were comfort, eating, and hygiene. Based on this finding, one NP was established listing the diagnoses, interventions and expected results to establish an ideal, though individualized, standard of nursing care to be provided to these patients. CONCLUSION: to understand oral mucositis is crucial to establish nursing care that includes prevention based on the implementation of an oral care plan. PMID:26039297

  6. Oral mucositis in cancer treatment: Natural history, prevention and treatment

    PubMed Central

    CAMPOS, MARIA INES DA CRUZ; CAMPOS, CELSO NEIVA; AARESTRUP, FERNANDO MONTEIRO; AARESTRUP, BEATRIZ JULIÃO VIEIRA

    2014-01-01

    Oral mucositis is a condition that is characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy. Oral mucositis is currently considered to be the most severe complication of anticancer therapy, affecting 40–80% of patients undergoing chemotherapy and almost all those undergoing radiotherapy of the head and neck. Although they do not prevent lesions from appearing, drugs for the treatment of oral mucositis are required to minimize its clinical aggressiveness and improve the nutritional status, hydration and quality of life of the affected patients. Furthermore, the prevention and control of oral ulcers is crucial for cancer prognosis, since the establishment of severe lesions may lead to temporary or permanent treatment discontinuation and compromise cancer control. The objective of this study was to present a review on this condition, its causes and its treatment to professional clinical dentists, in order to help minimize patient suffering. A search was conducted through PubMed, Lilacs and MedLine, to retrieve related articles published between 1994 and 2013. PMID:24772297

  7. Volatile Sulfur Compounds as a Predictor for Esophagogastroduodenal Mucosal Injury

    PubMed Central

    Yoo, Seung Hee; Jung, Hyeon Sik; Sohn, Wee Sik; Kim, Bong Hwan; Ku, Bon Ho; Kim, Young Saeng; Park, Sang Woon

    2008-01-01

    Background/Aims Halitosis is a symptom that bothers patients more socially than medically and its pathogenic mechanisms are unclear and treatment armamenterium is limited. Clinicians generally ignored active interventions. Since halitosis is closely associated with volatile sulfur compounds (VSCs), we used a Halimeter and gas chromatography to measure VSCs in patients with Helicobacter-pylori (H. pylori)-associated gastric diseases. Methods We categorized 72 patients with H. pylori infection into two groups based on their endoscopic findings: a non-erosive mucosal group (NE, n=24) and an erosive mucosal group (E, n=48). Halitosis was objectively assessed by applying either a Halimeter to breath air or gas chromatography to gastric juice. Simultaneously, the expression of VSC-generating enzyme was measured with reverse-transcriptase PCR using mRNA isolated from biopsy tissues. Results The levels of VSCs in exhaled breaths or aspirated gastric juices differed significantly between the NE and E groups (p<0.00001), suggesting that VSCs might reflect eroded epithelial damage induced by H. pylori infection. The expressions of cystathionine ?-synthase (CBS) and cystathionine ?-lyase (CSE) were broadly consistent with the degree of mucosal injury. Conclusions Erosive changes in esophagogastroduodenal mucosa were strongly correlated with increased VSC levels, suggesting that halitosis might result from H. pylori-associated erosive lesions. PMID:20485620

  8. A Vault Nanoparticle Vaccine Induces Protective Mucosal Immunity

    PubMed Central

    Champion, Cheryl I.; Kickhoefer, Valerie A.; Liu, Guangchao; Moniz, Raymond J.; Freed, Amanda S.; Bergmann, Liisa L.; Vaccari, Dana; Raval-Fernandes, Sujna; Chan, Ann M.; Rome, Leonard H.; Kelly, Kathleen A.

    2009-01-01

    Background Generation of robust cell-mediated immune responses at mucosal surfaces while reducing overall inflammation is a primary goal for vaccination. Here we report the use of a recombinant nanoparticle as a vaccine delivery platform against mucosal infections requiring T cell-mediated immunity for eradication. Methodology/Principal Findings We encapsulated an immunogenic protein, the major outer membrane protein (MOMP) of Chlamydia muridarum, within hollow, vault nanocapsules (MOMP-vaults) that were engineered to bind IgG for enhanced immunity. Intranasal immunization (i.n) with MOMP-vaults induced anti-chlamydial immunity plus significantly attenuated bacterial burden following challenge infection. Vault immunization induced anti-chlamydial immune responses and inflammasome formation but did not activate toll-like receptors. Moreover, MOMP-vault immunization enhanced microbial eradication without the inflammation usually associated with adjuvants. Conclusions/Significance Vault nanoparticles containing immunogenic proteins delivered to the respiratory tract by the i.n. route can act as “smart adjuvants” for inducing protective immunity at distant mucosal surfaces while avoiding destructive inflammation. PMID:19404403

  9. Epidemiology of mucosal human papillomavirus infection and associated diseases.

    PubMed

    Trottier, Helen; Burchell, Ann N

    2009-01-01

    This article describes the epidemiology of mucosal human papillomavirs (HPV) in adults and children, its mode of transmission and its associated diseases. Over 40 genotypes of HPV infect the epithelial lining of the anogenital tract and other mucosal areas of the body. HPV is the most common sexually transmitted infection globally, with high prevalences found in both females and males. The predominant route of transmission is via sexual contact, although mother-to-child transmission is also possible. HPV infection may exist asymptomatically or may induce the formation of benign or malignant tumours in the genital, oral or conjunctival mucosa. Although most infections clear spontaneously, those that persist result in substantial morbidity and invoke high costs associated with the treatment of clinically relevant lesions. Some 13-18 mucosal HPV types are considered to have high oncogenic potential. HPV is recognized unequivocally as the main causal factor for cervical cancer, and is further responsible for a substantial proportion of many other anogenital neoplasms and head and neck cancers. Infections with HPV types that have low oncogenic risk, such as HPV-6 and 11, are associated with benign lesions of the anogenital areas known as condylomata acuminata (genital warts), oral papillomas, conjunctival papillomas, as well as low-grade squamous intra-epithelial lesions of the cervix. Perinatally acquired HPV can also cause recurrent respiratory papillomatosis in infants and young children. The implementation of HPV vaccination therefore has the potential to prevent a substantial proportion of HPV-related disease in the future. PMID:19684442

  10. Mucosal vaccination and therapy with genetically modified lactic acid bacteria.

    PubMed

    Wells, Jerry

    2011-01-01

    Lactic acid bacteria (LAB) have proved to be effective mucosal delivery vehicles that overcome the problem of delivering functional proteins to the mucosal tissues. By the intranasal route, both live and killed LAB vaccine strains have been shown to elicit mucosal and systemic immune responses that afford protection against infectious challenges. To be effective via oral administration, frequent dosing over several weeks is required but new targeting and adjuvant strategies have clearly demonstrated the potential to increase the immunogenicity and protective immunity of LAB vaccines. Oral administration of Lactococcus lactis has been shown to induce antigen-specific oral tolerance (OT) to secreted recombinant antigens. LAB delivery is more efficient at inducing OT than the purified antigen, thus avoiding the need for purification of large quantities of antigen. This approach holds promise for new therapeutic interventions in allergies and antigen-induced autoimmune diseases. Several clinical and research reports demonstrate considerable progress in the application of genetically modified L. lactis for the treatment of inflammatory bowel disease (IBD). New medical targets are on the horizon, and the approval by several health authorities and biosafety committees of a containment system for a genetically modified L. lactis that secretes Il-10 should pave the way for new LAB delivery applications in the future. PMID:22129390

  11. Prolonged fasting increases glutathione biosynthesis in postweaned northern elephant seals

    PubMed Central

    Vázquez-Medina, José Pablo; Zenteno-Savín, Tania; Forman, Henry Jay; Crocker, Daniel E.; Ortiz, Rudy M.

    2011-01-01

    SUMMARY Northern elephant seals experience prolonged periods of absolute food and water deprivation (fasting) while breeding, molting or weaning. The postweaning fast in elephant seals is characterized by increases in the renin–angiotensin system, expression of the oxidant-producing protein Nox4, and NADPH oxidase activity; however, these increases are not correlated with increased oxidative damage or inflammation. Glutathione (GSH) is a potent reductant and a cofactor for glutathione peroxidases (GPx), glutathione-S transferases (GST) and 1-cys peroxiredoxin (PrxVI) and thus contributes to the removal of hydroperoxides, preventing oxidative damage. The effects of prolonged food deprivation on the GSH system are not well described in mammals. To test our hypothesis that GSH biosynthesis increases with fasting in postweaned elephant seals, we measured circulating and muscle GSH content at the early and late phases of the postweaning fast in elephant seals along with the activity/protein content of glutamate-cysteine ligase [GCL; catalytic (GCLc) and modulatory (GCLm) subunits], ?-glutamyl transpeptidase (GGT), glutathione disulphide reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), GST and PrxVI, as well as plasma changes in ?-glutamyl amino acids, glutamate and glutamine. GSH increased two- to four-fold with fasting along with a 40–50% increase in the content of GCLm and GCLc, a 75% increase in GGT activity, a two- to 2.5-fold increase in GR, G6PDH and GST activities and a 30% increase in PrxVI content. Plasma ?-glutamyl glutamine, ?-glutamyl isoleucine and ?-glutamyl methionine also increased with fasting whereas glutamate and glutamine decreased. Results indicate that GSH biosynthesis increases with fasting and that GSH contributes to counteracting hydroperoxide production, preventing oxidative damage in fasting seals. PMID:21430206

  12. Glutathione reductase: solvent equilibrium and kinetic isotope effects

    SciTech Connect

    Wong, K.K.; Vanoni, M.A.; Blanchard, J.S.

    1988-09-06

    Glutathione reductase catalyzes the NADPH-dependent reduction of oxidized glutathione (GSSG). The kinetic mechanism is ping-pong, and we have investigated the rate-limiting nature of proton-transfer steps in the reactions catalyzed by the spinach, yeast, and human erythrocyte glutathione reductases using a combination of alternate substrate and solvent kinetic isotope effects. With NADPH or GSSG as the variable substrate, at a fixed, saturating concentration of the other substrate, solvent kinetic isotope effects were observed on V but not V/K. Plots of Vm vs mole fraction of D2O (proton inventories) were linear in both cases for the yeast, spinach, and human erythrocyte enzymes. When solvent kinetic isotope effect studies were performed with DTNB instead of GSSG as an alternate substrate, a solvent kinetic isotope effect of 1.0 was observed. Solvent kinetic isotope effect measurements were also performed on the asymmetric disulfides GSSNB and GSSNP by using human erythrocyte glutathione reductase. The Km values for GSSNB and GSSNP were 70 microM and 13 microM, respectively, and V values were 62 and 57% of the one calculated for GSSG, respectively. Both of these substrates yield solvent kinetic isotope effects greater than 1.0 on both V and V/K and linear proton inventories, indicating that a single proton-transfer step is still rate limiting. These data are discussed in relationship to the chemical mechanism of GSSG reduction and the identity of the proton-transfer step whose rate is sensitive to solvent isotopic composition. Finally, the solvent equilibrium isotope effect measured with yeast glutathione reductase is 4.98, which allows us to calculate a fractionation factor for the thiol moiety of GSH of 0.456.

  13. CHARACTERIZATION OF DANSYLATED CYSTEINE, CYSTINE, GLUTATHIONE, AND GLUTATHIONE DISULFIDE BY NARROW BORE LIQUID CHROMATOGRAPHY - ELECTROSPRAY IONIZATION MASS SPECTROMETRY

    EPA Science Inventory

    A method using reversed phase high performance liquid chromtography/electrospray ionization-mass spectrometry (RP-LC/ESI-MS) has been developed to confirm the dientity of dansylated derivatives of cysteine (C) and glutathione (GSH), and their respective dimers, cystine (CSSC) and...

  14. Co-Induction of a Glutathione-S-transferase, a Glutathione Transporter and an ABC Transporter in Maize by Xenobiotics

    PubMed Central

    Liu, Zhiqian; Song, Xiaoyu; Li, Xuefeng; Wang, Chengju

    2012-01-01

    Glutathione conjugation reactions are one of the principal mechanisms that plants utilize to detoxify xenobiotics. The induction by four herbicides (2,4-D, atrazine, metolachlor and primisulfuron) and a herbicide safener (dichlormid) on the expression of three genes, ZmGST27, ZmGT1 and ZmMRP1, encoding respectively a glutathione-S-transferase, a glutathione transporter and an ATP-binding cassette (ABC) transporter was studied in maize. The results demonstrate that the inducing effect on gene expression varies with both chemicals and genes. The expression of ZmGST27 and ZmMRP1 was up-regulated by all five compounds, whereas that of ZmGT1 was increased by atrazine, metolachlor, primisulfuron and dichlormid, but not by 2,4-D. For all chemicals, the inducing effect was first detected on ZmGST27. The finding that ZmGT1 is activated alongside ZmGST27 and ZmMRP1 suggests that glutathione transporters are an important component in the xenobiotic detoxification system of plants. PMID:22792398

  15. Invasion of rabbit ileal tissue by Enterobacter cloacae varies with the concentration of OmpX in the outer membrane.

    PubMed Central

    de Kort, G; Bolton, A; Martin, G; Stephen, J; van de Klundert, J A

    1994-01-01

    The outer membrane protein OmpX of Enterobacter cloacae shows high amino acid homology with virulence proteins PagC and Rck from Salmonella typhimurium and with Ail from Yersinia enterocolitica. Here we demonstrate a role for OmpX in the invasion of rabbit ileal tissue by E. cloacae. An organ culture system was used for maintenance of rabbit gut tissue during the experiments. The invasiveness of three E. cloacae strains, which differed in OmpX content, were compared with each other and with that of Salmonella typhimurium TML (a highly invasive strain) and S. typhimurium LT7 (a noninvasive strain). There was no significant difference between the invasiveness of the wild type and that of an ompX deletion mutant strain of E. cloacae; they were equally as invasive or less invasive than S. typhimurium LT7. The invasiveness of an OmpX overproducer strain of E. cloacae was 10-fold higher than that of its immediate parent carrying only the multicopy plasmid, higher than that of S. typhimurium LT7, but lower than that of S. typhimurium TML. The invasiveness of E. cloacae thus varied directly with the level of OmpX in the outer membrane in rabbit ileal enterocytes challenged in situ. PMID:7927747

  16. Role of Meprins to Protect Ileal Mucosa of Crohn's Disease Patients from Colonization by Adherent-Invasive E. coli

    PubMed Central

    Vazeille, Emilie; Chambon, Christophe; Becker-Pauly, Christoph; Pender, Sylvia L. F.; Jakob, Christine; Müller, Stefan; Lottaz, Daniel; Darfeuille-Michaud, Arlette

    2011-01-01

    Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to adhere to and invade intestinal epithelial cells (IEC), and to survive within macrophages. The interaction of AIEC with IEC depends on bacterial factors mainly type 1 pili, flagella, and outer membrane proteins. In humans, proteases can act as host defence mechanisms to counteract bacterial colonization. The protease meprin, composed of multimeric complexes of the two subunits alpha and beta, is abundantly expressed in IECs. Decreased levels of this protease correlate with the severity of the inflammation in patients with inflammatory bowel disease. The aim of the present study was to analyze the ability of meprin to modulate the interaction of AIEC with IECs. In patients with ileal CD we observed decreased levels of meprins, in particular that of meprin ?. Dose-dependent inhibition of the abilities of AIEC strain LF82 to adhere to and invade intestinal epithelial T84 cells was observed when bacteria were pre-treated with both exogenous meprin ? and meprin ?. Dose-dependent proteolytic degradation of type 1 pili was observed in the presence of active meprins, but not with heat-inactivated meprins, and pretreatment of AIEC bacteria with meprins impaired their ability to bind mannosylated host receptors and led to decreased secretion of the pro-inflammatory cytokine IL-8 by infected T84 cells. Thus, decreased levels of protective meprins as observed in CD patients may contribute to increased AIEC colonization. PMID:21698174

  17. Unique microanatomy of ileal peyer's patches of the one humped camel (Camelus dromedarius) is not age-dependent.

    PubMed

    Zidan, Mohamed; Pabst, Reinhard

    2008-08-01

    The Peyer's patches (PP) have been intensely investigated in several species because this is an important entry site for antigens and infectious agents. There are many PP in the jejunum, and in some species such as ruminants, carnivores, and omnivores, a different continuous PP is found in the terminal ileum. This PP disappears with age in these species studied. So far the ileal PP (IPP) has only been examined in the camel by light microscopy. Therefore, the localization of ileal Peyer's patches in the dromedary camel at different ages, as well as the histology and ultrastructures were now investigated. The IPP were characteristically seen as dark rose-colored isolated structures in the shape of a cup, arranged in three irregular rows. The central row was antimesenteric. Each patch was formed by several mainly elongated dome regions flanked by intestinal villi. In cross-sections these domes appeared as short, wide villi. The domes were formed from lymphoid follicles covered with a typical dome-associated epithelium of enterocytes and M cells without any goblet cells. The M cells showed variable appearance depending on the functional status. The lymphoid follicles expressed clear germinal centers. High endothelial venules were localized in the interfollicular region. In contrast to other species the IPP were still present with a comparable macroscopic and histological structure in camels of 25 years of age. PMID:18449903

  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. Malignant Peripheral Nerve Sheath Tumour of Small Intestine Presenting as Ileo-Ileal Intussusception - A Rare Tumour with Unusual Complication

    PubMed Central

    Pandey, Diwakar; Akhtar, Azaz; Arsia, Ashish; Singh, Nain

    2015-01-01

    Malignant Peripheral Nerve Sheath Tumours (MPNST) arises from a peripheral nerve or exhibit nerve sheath differentiation on histology. Proximal portions of the upper and lower extremities and the trunk are the most common sites of occurrence. Around 50% are associated with Neurofibromatosis Type 1 (NF1) with incidence of two to five per cent in patients with NF1. The estimated incidence in general population without NF1 is 0.0001% of which gastrointestinal MPNST are extremely rare. A 45-year-old lady without pathological antecedent for NF1 was admitted with pain in right lower abdomen and multiple episodes of vomiting for 3 months. Preoperatively intussusception was diagnosed in the small bowel with USG and CECT abdomen showing characteristic target sign. On laparotomy Ileo-ileal intussusception (proximal ileum telescoping into distal ileum) was found 2 feet proximal to ileo-caecal junction with surrounding inflammed mesentery and presence of intraluminal tumour as lead point. Resection of involved segment of ileum along with its mesentery was done followed by ileo-ileal anastomosis. Histopathology was suggestive of high grade MPNST. Postoperative course and follow up for last 10 month is uneventful. This case is unique in terms of a rare tumour presenting with unusual complication and only one case had been reported so far in western literature.

  20. Comparison of proctocolectomy and ileal pouch-anal anastomosis to colectomy and ileorectal anastomosis in familial adenomatous polyposis.

    PubMed

    Koskenvuo, L; Mustonen, H; Renkonen-Sinisalo, L; Järvinen, H J; Lepistö, A

    2015-06-01

    Prophylactic surgical options for familial adenomatous polyposis (FAP) are either colectomy and ileorectal anastomosis (IRA) or proctocolectomy and ileal pouch-anal anastomosis (IPAA). The aim of this study was to analyse the short-term and long-term outcomes of these two operative techniques. All patients with FAP in Finland have been prospectively recorded in a database since 1963 were retrospectively reviewed in this analysis. Altogether 140 (61 %) colectomies with IRA and 88 (39 %) proctocolectomies with IPAA have been performed. Complications occurred in 28 (21 %) patients after IRA and in 26 (30 %) patients after IPAA. There were 15 (11 %) severe complications for IRA and 5 (6 %) for IPAA. Twenty-one (15 %) patients of the IRA group ended up in conventional ileostomy whereas 3 (3.4 %) patients of the IPAA group had their ileal reservoir converted to an ileostomy (p = 0.01). Cumulative survival for IRA was lower than for the IPAA (p = 0.03), but if accounting only for operations made after the IPAA era had commenced, there was no significant difference. IPAA was associated with improved long-term survival without an increase in postoperative complications. The risk of death after colectomy and IRA seemed to be predominantly related to the remaining risk of rectal cancer. Therefore, we favour proctocolectomy with IPAA as the prophylactic surgical procedure for FAP with intermediate or severe polyposis. PMID:25504366

  1. Bricker versus Wallace anastomosis: A meta-analysis of ureteroenteric stricture rates after ileal conduit urinary diversion

    PubMed Central

    Davis, Niall F.; Burke, John P.; McDermott, TED; Flynn, Robert; Manecksha, Rustom P.; Thornhill, John A.

    2015-01-01

    Introduction: Data comparing the incidence of ureteroenteric strictures for Bricker and Wallace anastomoses are limited. This study compares both anastomotic techniques in terms of ureteroenteric stricture rates after radical cystectomy and ileal conduit urinary diversion. Methods: Electronic databases (Medline, EMBASE, and Cochrane database) were searched for studies comparing Bricker and Wallace ureteroeneteric anastomoses for ileal conduit urinary diversion after radical cystectomy. Meta-analyses were performed using the random effects method. The primary outcome measure was to determine differences in postoperative ureteroenteric stricture rates for both surgical techniques. Four studies describing 658 patients met the inclusion criteria. The total number of ureters used for ureteroeneteric anastomoses was 1217 (545 in the Bricker group and 672 in the Wallace group). Results: There were no significant differences in age (p = 0.472), gender (p = 0.897), duration of follow-up (p = 0.168), and duration to stricture development between groups (p = 0.439). The overall stricture rate was 29 of 1217 (2.4%); 16 of 545 ureters (2.9%) in the Bricker group and 13 of 672 ureters (1.9%) in the Wallace group. The Bricker anastomosis was not associated with a significantly higher overall stricture rate compared to the Wallace ureteroenteric anastomosis (odds ratio: 1.393, 95% confidence interval: 0.441–4.394, p = 0.572). Conclusion: Accepting limitations in the available data, we found no significant difference in the incidence of ureteroenteric stricture for Bricker and Wallace anastomoses.

  2. 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. PMID:25521700

  3. Application of a spontaneously closed protective stoma in an ileal pouch-anal anastomosis: a preliminary study

    PubMed Central

    Wang, Jinhai; Ke, Bingxin; Lin, Jianjiang; Xu, Jiahe; Chen, Wenbin

    2015-01-01

    Background: To evaluate the application value of a spontaneously closed protective stoma (SCPS) in an ileal pouch-anal anastomosis, which is a novel procedure first performed in our hospital in 2008. Materials and methods: Two males cases with ulcerative colitis and one female with familial adenomatous polyposis were treated with colorectal surgery at the First Affiliated Hospital of Zhejiang University since March 2010. The surgery was designed as total proctocolectomy with an ileal pouch-anal anastomosis and SCPS. The surgical plan and procedure was determined with the patients after analyzing their hospitalized records and follow-up information. Results: No operation-induced death or anastomotic leakage occurred. One patient had a persistent fever and another patient presented with postoperative urinary retention. The average time until flatulence occurred post-SCPS was 26 days, and the average time until the removal of the postoperative stomal tube was 46 days that healed well. Conclusions: An SCPS can effectively protect the anastomosis with a simple operation and avoid the second surgery. Patients with ulcerative colitis require a two-stage operation, those who were in poor health and had a long history of hormone treatment even requiring a three-stage operation. However, a one- or two-stage operation could help alleviate pain for patients who require multiple surgeries and reduce economic burden. PMID:25785126

  4. IgG transport across mucosal barriers by neonatal Fc receptor for IgG and mucosal immunity

    Microsoft Academic Search

    Masaru Yoshida; Atsuhiro Masuda; Timothy T. Kuo; Kanna Kobayashi; Steven M. Claypool; Tetsuya Takagawa; Hiromu Kutsumi; Takeshi Azuma; Wayne I. Lencer; Richard S. Blumberg

    2006-01-01

    Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain significant quantities of IgG. The neonatal Fc receptor for IgG (FcRn) plays a major role in regulating host IgG levels and transporting IgG and associated antigens across polarized epithelial barriers. The FcRn can then recycle the IgG\\/antigen complex back across the intestinal barrier into the lamina propria for processing

  5. Glutathione, glutathione peroxidase, and selenium status in HIV-positive and HIV-negative adolescents and young adults1-3

    Microsoft Academic Search

    Charles B Stephensen; Grace S Marquis; Steven D Douglas; Laurie A Kruzich; Craig M Wilson

    Background:Antioxidantnutrientdeficienciesmayhastenthepro- gression of HIV disease by impairing antioxidant defenses. Objective:TheobjectiveofthestudywastodeterminewhetherHIV infectionisassociatedwithpoorseleniumstatusandlowantioxidant protection by glutathione and glutathione peroxidase (GPX). Design: In a cross-sectional study of 365 HIV-positive and HIV- negative adolescents and young adults, we examined the relation of plasma selenium, whole-blood glutathione, and whole-blood GPX to HIV status, disease severity, immune activation, and oxidative damage. Results: Selenium deficiency (plasma selenium

  6. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia

    PubMed Central

    Dillon, SM; Lee, EJ; Kotter, CV; Austin, GL; Dong, Z; Hecht, DK; Gianella, S; Siewe, B; Smith, DM; Landay, AL; Robertson, CE; Frank, DN; Wilson, CC

    2014-01-01

    HIV-1 infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T cell activation, inflammation and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1 infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared to uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1 infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation and blood T cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection. PMID:24399150

  7. The role of oral flora in the development of chemotherapy-induced oral mucositis.

    PubMed

    Stringer, Andrea M; Logan, Richard M

    2015-02-01

    Chemotherapy-induced mucositis is considered to be a major oncological problem, caused by the cytotoxic effects of cancer chemotherapy. In the last 10 years, there have been significant advances in the understanding of mucositis pathobiology. At the basic level, it is now well-understood that it is not just an epithelial process, but rather a complex interaction between epithelial and connective tissue compartments. There is also potential interaction between the oral microenvironment and the development of mucositis. Changes occur in the resident oral flora (commensal) throughout cancer treatment, and it is conceivable that these organisms and changes that occur may have an influence on the development of mucosal toxicity associated with cancer treatment. The aim of this review was to examine the potential contributions of oral microflora in the pathobiology of mucositis and identify pathways and interactions that could be targeted for therapeutic management of mucositis. PMID:24494824

  8. Approaches to tuberculosis mucosal vaccine development using nanoparticles and microparticles: a review.

    PubMed

    Caetano, Liliana Aranha; Almeida, António José; Gon?alves, Lídia Maria Diogo

    2014-09-01

    Next-generation vaccines for tuberculosis should be designed to prevent the infection and to achieve sterile eradication of Mycobacterium tuberculosis. Mucosal vaccination is a needle-free vaccine strategy that provides protective immunity against pathogenic bacteria and viruses in both mucosal and systemic compartments, being a promising alternative to current tuberculosis vaccines. Micro and nanoparticles have shown great potential as delivery systems for mucosal vaccines. In this review, the immunological principles underlying mucosal vaccine development will be discussed, and the application of mucosal adjuvants and delivery systems to the enhancement of protective immune responses at mucosal surfaces will be reviewed, in particular those envisioned for oral and nasal routes of administration. An overview of the essential vaccine candidates for tuberculosis in clinical trials will be provided, with special emphasis on the potential different antigens and immunization regimens. PMID:25992458

  9. The structures of human glutathione transferase P1-1 in complex with glutathione and various inhibitors at high resolution 1 1 Edited by R. Huber

    Microsoft Academic Search

    Aaron J Oakley; Mario Lo Bello; Andrea Battistoni; Giorgio Ricci; Jamie Rossjohn; Hugo O Villar; Michael W Parker

    1997-01-01

    The human pi-class glutathione S-transferase (hGST P1-1) is a target for structure-based inhibitor design with the aim of developing drugs that could be used as adjuvants in chemotherapeutic treatment. Here we present seven crystal structures of the enzyme in complex with substrate (glutathione) and two inhibitors (S-hexyl glutathione and ?-glutamyl-(S-benzyl)cysteinyl-d-phenylglycine). The binding of the modified glutathione inhibitor, ?-glutamyl-(S-benzyl)cysteinyl-d-phenylglycine, has been

  10. Glutathione, glutathione-dependent and antioxidant enzymes in mussel, Mytilus galloprovincialis, exposed to metals under field and laboratory conditions: implications for the use of biochemical biomarkers

    Microsoft Academic Search

    Francesco Regoli; Giovanni Principato

    1995-01-01

    The effects of exposure to metals under and laboratory conditions were investigated in the Mediterranean mussel Mytilus galloprovincialis. The examined biological responses included the concentrations of heavy metals, the level of glutathione, and the activity of several enzymes selected among glutathione-dependent oxidoreductases and hydrolases: glutathione reductase. EC1.6.4.2; glyoxalase I, EC4.4.1.5; glyoxalase II, EC3.1.2.6; glutathione S-transferases, EC2.5.1.18; Se-dependent, EC1 11.1.9 and

  11. [Glutathione system in erythrocytes and blood plasma in strokes and dyscirculatory encephalopathy].

    PubMed

    Kolesnichenko, L S; Kulinski, V I; Shprakh, V V; Bardymov, V V; Verlan, N V; Gubina, L P; Pensionerova, G A; Sergeeva, M P; Stanevich, L M; Filippova, G T

    2007-01-01

    In dyscirculatory encephalopathy and moderate ischemic stroke there are single changes of components of glutathione metabolism. In moderate and severe ischemic stroke frequent and considerable changes have been revealed. Changes in hemorrhagic stroke are also expressed. An increase of activities of glutathione peroxidase and glutathione transferase is the most typical, rarely the increase of glutathione reductase and GSH is observed. The increase of enzymes activity was absent at the delayed oneset of treatment (more than 3 days) and in severe cases patients who died later. Glutathione system is important in the tolerance to cerebral ischemia. PMID:18035726

  12. Newly identified protein Imi1 affects mitochondrial integrity and glutathione homeostasis in Saccharomyces cerevisiae.

    PubMed

    Kowalec, Piotr; Grynberg, Marcin; Paj?k, Beata; Socha, Anna; Winiarska, Katarzyna; Fronk, Jan; Kurlandzka, Anna

    2015-09-01

    Glutathione homeostasis is crucial for cell functioning. We describe a novel Imi1 protein of Saccharomyces cerevisiae affecting mitochondrial integrity and involved in controlling glutathione level. Imi1 is cytoplasmic and, except for its N-terminal Flo11 domain, has a distinct solenoid structure. A lack of Imi1 leads to mitochondrial lesions comprising aberrant morphology of cristae and multifarious mtDNA rearrangements and impaired respiration. The mitochondrial malfunctioning is coupled to significantly decrease the level of intracellular reduced glutathione without affecting oxidized glutathione, which decreases the reduced/oxidized glutathione ratio. These defects are accompanied by decreased cadmium sensitivity and increased phytochelatin-2 level. PMID:26091838

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

    Microsoft Academic Search

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

    1993-01-01

    Antibodies to the cytosolic leucocyte L1 protein (or calprotectin) were examined for reactivity with macrophages, neutrophils, and eosinophils identified by paired immunofluorescence staining in sections of normal human ileal mucosa, including Peyer's patches. Macrophages were recognised by expression of the myelomonocytic antigen CD68 (monoclonal antibody KP1). Neutrophilic granulocytes were identified by their content of neutrophil elastase, and eosinophilic granulocytes by

  14. Dietary supplementation with benzoic acid improves apparent ileal digestibility of total nitrogen and increases villous height and caecal microbial diversity in weaner pigs

    Microsoft Academic Search

    D. Halas; C. F. Hansen; D. J. Hampson; B. P. Mullan; J. C. Kim; R. H. Wilson; J. R. Pluske

    2010-01-01

    The purpose of this study was to evaluate the effects of feeding two different levels of benzoic acid (BA) and three different levels of inulin (IN) on weaner pig performance, coefficient of apparent ileal digestibility of total nitrogen (CAIDN), small intestinal structure, diversity of caecal microbiota, indices of bacterial fermentation, incidence of post-weaning diarrhea (PWD) and enterotoxigenic Escherichia coli (ETEC)

  15. The Effect of Thermal Processing and Enzyme Treatments of Soybean Meal on Growth Performance, Ileal Nutrient Digestibilities, and Chyme Characteristics in Broiler Chicks

    Microsoft Academic Search

    G. J. P. MARSMAN; H. GRUPPEN; R. P. KWAKKEL; M. W. A. VERSTEGEN; A. G. J. VORAGEN

    1997-01-01

    Effects of thermal processing (toasting or extrusion) of untoasted soybean meal on growth perfor- mance, apparent ileal nutrient digestibilities, and chyme characteristics were studied in broiler chicks fed diets with soybean meal as the main protein source. Effects of increasing shear forces during extrusion as well as enzyme treatments (protease and carbohydrase) were also studied. When compared with toasting, extrusion

  16. Effect of extrusion under controlled temperature and moisture conditions on ileal apparent amino acid and starch digestibility in peas determined with young broilers

    Microsoft Academic Search

    W. Al-Marzooqi; J. Wiseman

    2009-01-01

    The objective of the experimental programme was to examine the influence of extrusion of peas under controlled temperature and moisture conditions on coefficient of ileal apparent digestibility (CIAD) of amino acids and to examine the changes to starch structure (crystallisation) and subsequent effects on CIAD of starch in young broilers. Experiment 1 used one pea cultivar (2.94mg trypsin inhibitor units

  17. Comparison of sample source (excreta or ileal digesta) and age of broiler chick on measurement of apparent metabolisable energy of local feed ingredients

    Microsoft Academic Search

    Waqas Masood; Sohail Hassan Khan; Shaukat Ali Bhatti; Abida Parveen

    2011-01-01

    The present study was designed to measure the metabolisable energy (ME) values of local feed ingredients, namely corn, rice tips, rice polish, soybean meal, canola meal and sunflower meal for commercial broilers at 18, 26 and 34 days of age using total fecal collection and external marker in ileal and fecal samples. For this purpose, 240 birds of same weight

  18. Comparison of sample source (excreta or ileal digesta) and age of broiler chick on measurement of apparent metabolizable energy of local feed ingredients

    Microsoft Academic Search

    Waqas Masood; Sohail Hassan Khan; Shaukat Ali Bhatti; Abida Parveen

    2011-01-01

    The present study was designed to measure the metabolizable energy (ME) values of local feed ingredients, namely corn, rice tips, rice polish, soybean meal, canola meal and sunflower meal for commercial broilers at 18, 26 and 34 days of age using total fecal collection and external marker in ileal and fecal samples. For this purpose, 240 birds of same weight

  19. Correlation of Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinase Expression in Ileal Carcinoids, Lymph Nodes and Liver Metastasis with Prognosis and Survival

    Microsoft Academic Search

    Petra Voland; Sophie Besig; Roland Rad; Thomas Braun; Dorothee M. Baur; Aurel Perren; Rupert Langer; Heinz Höfler; Christian Prinz

    2009-01-01

    Purpose: Ileal carcinoids are gut epithelial tumors originating from serotonin-containing enterochromaffin (EC) cells. Therapeutic options for effectively inhibiting the growth and spread of metastatic carcinoids are still limited. We aimed to identify the role of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) during tumor development and metastasis. Patients and Methods: Tissue samples were obtained from surgically treated patients.

  20. Implementation of a clinical pathway decreases length of stay and hospital charges for patients undergoing total colectomy and ileal pouch\\/anal anastomosis

    Microsoft Academic Search

    Stephen B Archer; Robert J Burnett; Linda V Flesch; Scott C Hobler; Robert H Bower; Michael S Nussbaum; Josef E Fischer

    1997-01-01

    Background. Clinical pathways are increasingly being used by hospitals to improve efficiency in the care of certain patient populations; however, little prospective data are available to support their use. This study examined whether using a clinical pathway for patients undergoing ileal pouch\\/anal anastomosis, a complex procedure in which we had extensive practical experience, affected hospital charges or length of stay

  1. Effect of Fumaric Acid and Dietary Buffering Capacity on Ileal and Fecal Amino Acid Digestibilities in Early-Weaned Pigs1,2

    Microsoft Academic Search

    R. Blank; R. Mosenthin; W. C. Sauer; S. Huang

    Experiments were conducted to deter- mine the effect of fumaric acid supplementation and buffering capacity of the diet on ileal and fecal digest- ibilities of CP, GE, and amino acids in early-weaned pigs. In two experiments, 12 pigs each were weaned at 14 d of age and fitted with a simple T-cannula at the distal ileum between 15 and 17

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

    PubMed Central

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

    1996-01-01

    Primary sclerosing cholangitis (PSC), present in 5% of patients with ulcerative colitis, may be associated with pouchitis after ileal pouch-anal anastomosis. The cumulative frequency of pouchitis in patients with and without PSC who underwent ileal pouch-anal anastomosis for ulcerative colitis was determined. A total of 1097 patients who had an ileal pouch-anal anastomosis for ulcerative colitis, 54 with associated PSC, were studied. Pouchitis was defined by clinical criteria in all patients and by clinical, endoscopic, and histological criteria in 83% of PSC patients and 85% of their matched controls. PSC was defined by clinical, radiological, and pathological findings. One or more episodes of pouchitis occurred in 32% of patients without PSC and 63% of patients with PSC. The cumulative risk of pouchitis at one, two, five, and 10 years after ileal pouch-anal anastomosis was 15.5%, 22.5%, 36%, and 45.5% for the patients without PSC and 22%, 43%, 61%, and 79% for the patients with PSC. In the PSC group, the risk of pouchitis was not related to the severity of liver disease. In conclusion, the strong correlation between PSC and pouchitis suggest a common link in their pathogenesis. PMID:8801203

  3. 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...

  4. Nonmucosal Alphavirus Vaccination Stimulates a Mucosal Inductive Environment in the Peripheral Draining Lymph Node1

    PubMed Central

    Thompson, Joseph M.; Nicholson, Michael G.; Whitmore, Alan C.; Zamora, Melodie; West, Ande; Iwasaki, Akiko; Staats, Herman F.; Johnston, Robert E.

    2009-01-01

    The strongest mucosal immune responses are induced following mucosal Ag delivery and processing in the mucosal lymphoid tissues, and much is known regarding the immunological parameters which regulate immune induction via this pathway. Recently, experimental systems have been identified in which mucosal immune responses are induced following nonmucosal Ag delivery. One such system, footpad delivery of Venezuelan equine encephalitis virus replicon particles (VRP), led to the local production of IgA Abs directed against both expressed and codelivered Ags at multiple mucosal surfaces in mice. In contrast to the mucosal delivery pathway, little is known regarding the lymphoid structures and immunological components that are responsible for mucosal immune induction following nonmucosal delivery. In this study, we have used footpad delivery of VRP to probe the constituents of this alternative pathway for mucosal immune induction. Following nonmucosal VRP delivery, J chain-containing, polymeric IgA Abs were detected in the peripheral draining lymph node (DLN), at a time before IgA detection at mucosal surfaces. Further analysis of the VRP DLN revealed up-regulated ?4?7 integrin expression on DLN B cells, expression of mucosal addressin cell adhesion molecule 1 on the DLN high endothelia venules, and production of IL-6 and CC chemokines, all characteristics of mucosal lymphoid tissues. Taken together, these results implicate the peripheral DLN as an integral component of an alternative pathway for mucosal immune induction. A further understanding of the critical immunological and viral components of this pathway may significantly improve both our knowledge of viral-induced immunity and the efficacy of viral-based vaccines. PMID:18566424

  5. Local antimicrobial therapy of oral mucositis in paediatric patients undergoing bone marrow transplantation.

    PubMed

    Bondi, E; Baroni, C; Prete, A; Gatti, M; Carrassi, A; Lodi, G; Porter, S R

    1997-09-01

    The present investigation has examined the clinical benefits of tobramycin, polymyxin E and amphotericin therapy in the management of oral mucositis in children undergoing chemotherapy prior to bone marrow transplantation. Tobramycin, polymyxin E, and amphotericin reduced the degree of oral mucositis more than conventional therapy of diphenhydramine, Maalox, and local analgesic. While there was a statistically significant fall in the severity of the mucositis with tobramycin, polymyxin E and amphotericin, this was unlikely to be of practical benefit. PMID:9415330

  6. Oral mucositis in patients treated with chemotherapy for solid tumors: a retrospective analysis of 150 cases

    Microsoft Academic Search

    J. E. Raber-Durlacher; N. I. Weijl; M. Abu Saris; B. de Koning; A. H. Zwinderman; S. Osanto

    2000-01-01

    The incidence and the severity of chemotherapy-associated oral mucositis were determined in a retrospective analysis of 150\\u000a patients with various solid tumors. In addition, possible risk factors for the development of mucositis were identified. Patients\\u000a were treated with chemotherapeutic regimens appropriate to tumor type and disease stage on an in- or outpatient basis. Mucositis\\u000a was scored using the World Health

  7. Novel physiological roles for glutathione in sequestering acetaldehyde to confer acetaldehyde tolerance in Saccharomyces cerevisiae.

    PubMed

    Matsufuji, Yoshimi; Yamamoto, Kohei; Yamauchi, Kosei; Mitsunaga, Tohru; Hayakawa, Takashi; Nakagawa, Tomoyuki

    2013-01-01

    In this work, we identified novel physiological functions of glutathione in acetaldehyde tolerance in Saccharomyces cerevisiae. Strains deleted in the genes encoding the enzymes involved in glutathione synthesis and reduction, GSH1, GSH2 and GLR1, exhibited severe growth defects compared to wild-type under acetaldehyde stress, although strains deleted in the genes encoding glutathione peroxidases or glutathione transferases did not show any growth defects. On the other hand, intracellular levels of reduced glutathione decreased in the presence of acetaldehyde in response to acetaldehyde concentration. Moreover, we show that glutathione can trap a maximum of four acetaldehyde molecules within its molecule in a non-enzymatic manner. Taken together, these findings suggest that glutathione has an important role in acetaldehyde tolerance, as a direct scavenger of acetaldehyde in the cell. PMID:22615054

  8. Effects of cold stress on glutathione and related enzymes in rat erythrocytes

    NASA Astrophysics Data System (ADS)

    Ohno, Hideki; Kondo, Takahito; Fujiwara, Yutaka; Tagami, Sei-Ichi; Kuroshima, Akihiro; Kawakami, Yoshikazu

    1991-06-01

    Effects of acute and chronic cold stress on glutathione and related enzymes in rat erythrocytes were investigated. Blood from both cold-acclimated (CA) and cold-adapted (CG) rats had significantly lower concentrations of glutathione than blood from control animals. Superoxide dismutase activity was increased significantly in CA rats and tended to rise in CG rats. Activity of glutathione peroxidase in erythrocytes was inconsistent in that it tended to increase in CA rats but decreased significantly in CG rats. The results may imply that CG rats suffered deleterious effects of hydrogen peroxide. On the other hand, there were marked decreases in glutathione peroxidase and glutathione reductase activities in acutely cold-exposed rats in conjunction with unchanged levels of glutathione. In all treatments the state of riboflavin metabolism was estimated to be adequate, since no increases were observed in the erythrocyte glutathione reductase activity coefficient.

  9. Streptococcus pneumoniae Uses Glutathione To Defend against Oxidative Stress and Metal Ion Toxicity

    PubMed Central

    Potter, Adam J.; Trappetti, Claudia

    2012-01-01

    The thiol-containing tripeptide glutathione is an important cellular constituent of many eukaryotic and prokaryotic cells. In addition to its disulfide reductase activity, glutathione is known to protect cells from many forms of physiological stress. This report represents the first investigation into the role of glutathione in the Gram-positive pathogen Streptococcus pneumoniae. We demonstrate that pneumococci import extracellular glutathione using the ABC transporter substrate binding protein GshT. Mutation of gshT and the gene encoding glutathione reductase (gor) increases pneumococcal sensitivity to the superoxide generating compound paraquat, illustrating the importance of glutathione utilization in pneumococcal oxidative stress resistance. In addition, the gshT and gor mutant strains are hypersensitive to challenge with the divalent metal ions copper, cadmium, and zinc. The importance of glutathione utilization in pneumococcal colonization and invasion of the host is demonstrated by the attenuated phenotype of the gshT mutant strain in a mouse model of infection. PMID:22984260

  10. Evaluation of topical external medicine for 5-fluorouracil-induced oral mucositis in hamsters.

    PubMed

    Mitsuhashi, Hiromi; Suemaru, Katsuya; Li, Bingjin; Cui, Ranji; Araki, Hiroaki

    2006-12-01

    Oral ulcerative mucositis is a common and painful toxicity associated with chemotherapy for cancer. Current treatment for chemotherapy-induced oral mucositis is largely palliative, and no adequate treatment with conclusive evidence exists. The purpose of this study was to evaluate the potential effectiveness of the topical external medicines used in clinical settings, and the authors investigated the effects of 1% azulene ointment, 0.12% dexamethasone ointment, and polaprezinc-sodium alginate suspension on an animal model for oral mucositis induced by chemotherapy. Oral mucositis was induced in hamsters through a combination treatment of 5-fluorouracil and mild abrasion of the cheek pouch. Each drug was administered topically to the oral mucosa of hamsters, and the process of healing of damaged oral mucositis was examined by measuring the size of the mucositis. Azulene ointment did not reduce the size of the mucositis compared with the vaseline-treated control group. Polaprezinc-sodium alginate suspension significantly improved the recovery from 5-fluorouracil-induced damage. In contrast, local treatment with dexamethasone exacerbated the mucositis markedly. These results suggested the healing effect of polaprezinc-sodium alginate suspension and the risk of steroids to severe oral mucositis induced by chemotherapy. PMID:17046745

  11. Effects of Elevated Cytosolic Glutathione Reductase Activity on the Cellular Glutathione Pool and Photosynthesis in Leaves under Normal and Stress Conditions

    PubMed Central

    Foyer, Christine; Lelandais, Maud; Galap, Camille; Kunert, Karl Josef

    1991-01-01

    Tobacco (Nicotiana tabacum var Samsun) was transformed using the bacterial gor gene coding for the enzyme glutathione reductase. Transgenic plants were selected by their kanamycin resistence and expression of the bacterial gor gene. After separation by isoelectric focusing techniques, leaf extracts from transgenic plants having both native and bacterial glutathione reductase activity gave, in addition to the six bands of the native enzyme, two further closely running isoenzymes. These additional bands originating from the expression of the bacterial gor gene were nonchloroplastic. Leaves from transgenic plants had two- to 10-fold higher glutathione reductase activity than non-transgenic controls. The amount of extractable glutathione reductase activity obtained in transgenic plants was dependent on leaf age and the conditions to which leaves were exposed. Both light and exposure to methylviologen increased leaf glutathione reductase activity. Elevated levels of cytosolic glutathione reductase activity in transgenic plants had no effect on the amount or reduction state of the reduced glutathione/oxidized glutathione pool under optimal conditions or oxidative conditions induced by methylviologen. The glutathione pool was unaltered despite the oxidation-dependent loss of CO2 assimilation and oxidation of enzymes involved in photosynthesis. However, the reduction state of the ascorbate pool was greater in transgenic plants relative to nontransgenic controls following illumination of methylviologen-treated leaf discs. Therefore, we conclude that in the natural state glutathione reductase is present in tobacco at levels above those required for maximal operation of the ascorbate-glutathione pathway. ImagesFigure 1Figure 3Figure 4Figure 5Figure 6Figure 7 PMID:16668524

  12. Role of Glutathione in Cancer Progression and Chemoresistance

    PubMed Central

    Traverso, Nicola; Ricciarelli, Roberta; Nitti, Mariapaola; Marengo, Barbara; Furfaro, Anna Lisa; Pronzato, Maria Adelaide; Marinari, Umberto Maria; Domenicotti, Cinzia

    2013-01-01

    Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and disturbances in GSH homeostasis are involved in the etiology and progression of many human diseases including cancer. While GSH deficiency, or a decrease in the GSH/glutathione disulphide (GSSG) ratio, leads to an increased susceptibility to oxidative stress implicated in the progression of cancer, elevated GSH levels increase the antioxidant capacity and the resistance to oxidative stress as observed in many cancer cells. The present review highlights the role of GSH and related cytoprotective effects in the susceptibility to carcinogenesis and in the sensitivity of tumors to the cytotoxic effects of anticancer agents. PMID:23766865

  13. Application of a two-stage temperature control strategy for enhanced glutathione production in the batch fermentation by Candida utilis

    Microsoft Academic Search

    Gongyuan Wei; Yin Li; Guocheng Du; Jian Chen

    2003-01-01

    In batch culture for glutathione production with Candida utilis, a higher temperature (30 °C) was required to hasten cell growth while a lower temperature (26 °C) was needed to increase the production of glutathione. A two-stage temperature control strategy was used to enhance both the yield and the productivity of glutathione. As a result, glutathione production was increased by 5% and 23%

  14. Selenium-dependent glutathione peroxidase modules encoded by RNA viruses

    Microsoft Academic Search

    W. Zhang; C. S. Ramanathan; R. G. Nadimpalli; A. A. Bhat; A. G. Cox; E. W. Taylor

    1999-01-01

    Glutathione peroxidase (GPx) is the prototypical eukaryotic selenoprotein, with the rare amino acid selenocysteine (Sec) at\\u000a the enzyme active site, encoded by the UGA codon in RNA. A DNA virus,Molluscum contagiosum, has now been shown to encode a functional selenium-dependent GPx enzyme. Using modifications of conventional sequence database\\u000a searching techniques to locate potential viral GPx modules, combined with structurally guided

  15. Characterization of the glutathione binding site of aldose reductase.

    PubMed

    Ramana, K V; Dixit, B L; Srivastava, S; Bhatnagar, A; Balendiran, G K; Watowich, S J; Petrash, J M; Srivastava, S K

    2001-01-30

    Despite extensive investigations, the physiological role of the polyol pathway enzyme-aldose reductase (AR) remains obscure. While the enzyme reduces glucose in vivo and in vitro, kinetic and structural studies indicate inefficient carbohydrate binding to the active site of the enzyme. The active site is lined by hydrophobic residues and appears more compatible with the binding of medium- to long-chain aliphatic aldehydes or hydrophobic aromatic aldehydes. In addition, our recent studies show that glutathione (GS) conjugates are also reduced efficiently by the enzyme. For instance, the GS conjugate of acrolein is reduced with a catalytic efficiency 1000-fold higher than the parent aldehyde, indicating specific recognition of glutathione by the active site residues of AR. An increase in the catalytic efficiency upon glutathiolation was also observed with trans-2-nonenal, trans-2-hexenal and trans, trans-2,4-decadienal, establishing that enhancement of catalytic efficiency was specifically due to the glutathione backbone and not specific to the aldehyde. Structure-activity relationships with substitution or deletion of amino acids of GSH indicated specific interactions of the active site with gamma-Glu1 and Cys of GSH. Molecular modeling revealed that the glutathione-propanal conjugate could bind in two distinct orientations. In orientation 1, gamma-Glu1 of the conjugate interacts with Trp20, Lys21 and Val47, and Gly3 interacts with Ser302 and Leu301, whereas in orientation 2, the molecule is inverted with gamma-Glu1 interacting with Ser302, and Leu301. Taken together, these data suggest that glutathiolation of aldehydes enhances their compatibility with the AR active site, which may be of physiological significance in detoxification of endogenous and xenobiotic aldehydes. PMID:11306073

  16. Methods for the Determination of Plasma or Tissue Glutathione Levels

    PubMed Central

    Tipple, Trent E.; Rogers, Lynette K.

    2013-01-01

    We present two different methods for determining levels of glutathione in complex biological samples and plasma. The DTNB/GR enzyme recycling method is sensitive and requires no specialized equipment. The HPLC method is particularly useful for situations in which sample amounts are limited. Detailed instructions for performing each method as well as the advantages and disadvantages of each are discussed in this Chapter. PMID:22669674

  17. Mucosal barrier, bacteria and inflammatory bowel disease: possibilities for therapy.

    PubMed

    Merga, Yvette; Campbell, Barry J; Rhodes, Jonathan M

    2014-01-01

    The mucosal barrier has three major components, the mucus layer, the epithelial glycocalyx and the surface epithelium itself, whose integrity largely depends on tight junction function. In health, there is relatively little direct interaction between the luminal microbiota and the epithelium - the continuous mucus layer in the colon keeps the surface epithelium out of contact with bacteria and the ileo-caecal valve ensures that the distal small intestine is relatively microbe free. Most interaction takes place at the Peyer's patches in the distal ileum and their smaller colonic equivalents, the lymphoid follicles. Peyer's patches are overlain by a 'dome' epithelium, 5% of whose cells are specialised M (microfold) epithelial cells, which act as the major portal of entry for bacteria. There are no goblet cells in the dome epithelium and M cells have a very sparse glycocalyx allowing easy microbial interaction. It is intriguing that the typical age range for the onset of Crohn's disease (CD) is similar to the age at which the number of Peyer's patches is greatest. Peyer's patches are commonly the sites of the initial lesions in CD and the 'anti-pancreatic' antibody associated with CD has been shown to have as its epitope the glycoprotein 2 that is the receptor for type-1 bacterial fimbrial protein (fimH) on M cells. There are many reasons to believe that the mucosal barrier is critically important in the pathogenesis of inflammatory bowel disease (IBD). These include (i) associations between both CD and ulcerative colitis (UC) with genes that are relevant to the mucosal barrier; (ii) increased intestinal permeability in unaffected relatives of CD patients; (iii) increased immune reactivity against bacterial antigens, and (iv) animal models in which altered mucosal barrier, e.g. denudation of the mucus layer associated with oral dextran sulphate in rodents, induces colitis. Whilst some IBD patients may have genetic factors leading to weakening of the mucosal barrier, it is likely that environmental factors may be even more important. Some may be subtle and indirect, e.g. the effects of stress on the mucosa barrier, whilst others may be more obvious, e.g. the effect of pathogen-related gastroenteritis, known often to act as trigger for IBD relapse. We have also been very interested in the potentially harmful effects of ingested detergents - either by contamination of cutlery by inadequate rinsing or via ingestion of processed foods containing permitted emulsifiers. In vitro and ex vivo studies show that even very small trace amounts of these surfactants can greatly increase bacterial translocation. Implications for therapy are not yet so obvious. We advise our IBD patients to avoid processed foods containing emulsifiers and to rinse their dishes well - whilst accepting that there is no direct evidence yet to support this. Therapies that aim to enhance the mucosal barrier have yet to come to market, but trials of enteric-delivered phosphatidylcholine in UC are promising. The faecal concentration of mucus-degrading bacterial enzymes (particularly proteases, sulphatases and sialidases) correlates with disease activity in UC, and these represent good targets for therapy. PMID:24969297

  18. Isolation and characterization of a mucosal triacylglycerol pool undergoing hydrolysis

    SciTech Connect

    Tipton AD IV; Frase, S.; Mansbach, C.M. II (Univ. of Tennessee, Memphis (USA))

    1989-12-01

    Absorbed and processed mucosal neutral lipid has been shown to be composed of at least two pools of triacylglycerol. One is likely to subserve chylomicron formation, and the other appears to be transported from the intestine via a nonlymphatic route. In the present study, 50 +/- 5% of the mucosal lipid pellets was centrifuged at 75,000 g.min (low-speed pellet (LSP)). Discontinuous sucrose density gradient centrifugation of LSP showed that 61 +/- 7% of the lipid banded at the 0.25-0.86 M sucrose interface. Neutral lipid analysis showed that this subfraction was only 58% triacylglycerol, suggesting it was undergoing hydrolysis. Active lipolytic activity in vitro was found on incubation. The lipase had an alkaline pH optimum (pH 8.5) and persisted despite pancreatic ductular diversion. Lipolysis in vivo in a LSP fraction was shown by infusing (14C)glyceryltrioleate for 3.5 h followed by (3H)glyceryltrioleate for 30 min. Discontinuous sucrose density centrifugation of the LSP followed by an analysis of the lipids at the 0.25-0.86 M sucrose interface showed that 14C-neutral lipids were only 70 +/- 6% triacylglycerol, whereas 3H-neutral lipids were 88 +/- 2% triacylglycerol. 3H entered LSP slowly compared with the floating lipid in the same centrifuge tube. These studies suggest both in vivo and in vitro mucosal lipolysis by a specific, alkaline-active lipase. The turnover rate of LSP is likely to be slow by comparison with neutral lipid floating to the top of the centrifuge tube.

  19. Equine Stomachs Harbor an Abundant and Diverse Mucosal Microbiota

    PubMed Central

    Perkins, G. A.; Burton, A. J.; Erb, H. N.; McDonough, S. P.; McDonough, P. L.; Parker, J.; Rosenthal, R. L.; Wiedmann, M.; Dowd, S. E.

    2012-01-01

    Little is known about the gastric mucosal microbiota in healthy horses, and its role in gastric disease has not been critically examined. The present study used a combination of 16S rRNA bacterial tag-encoded pyrosequencing (bTEFAP) and fluorescence in situ hybridization (FISH) to characterize the composition and spatial distribution of selected gastric mucosal microbiota of healthy horses. Biopsy specimens of the squamous, glandular, antral, and any ulcerated mucosa were obtained from 6 healthy horses by gastroscopy and from 3 horses immediately postmortem. Pyrosequencing was performed on biopsy specimens from 6 of the horses and yielded 53,920 reads in total, with 631 to 4,345 reads in each region per horse. The microbiome segregated into two distinct clusters comprised of horses that were stabled, fed hay, and sampled at postmortem (cluster 1) and horses that were pastured on grass, fed hay, and biopsied gastroscopically after a 12-h fast (cluster 2). The types of bacteria obtained from different anatomic regions clustered by horse rather than region. The dominant bacteria in cluster 1 were Firmicutes (>83% reads/sample), mainly Streptococcus spp., Lactobacillus spp. and, Sarcina spp. Cluster 2 was more diverse, with predominantly Proteobacteria, Bacteroidetes, and Firmicutes, consisting of Actinobacillus spp. Moraxella spp., Prevotella spp., and Porphyromonas spp. Helicobacter sp. sequences were not identified in any of 53,920 reads. FISH (n = 9) revealed bacteria throughout the stomach in close apposition to the mucosa, with significantly more Streptococcus spp. present in the glandular region of the stomach. The equine stomach harbors an abundant and diverse mucosal microbiota that varies by individual. PMID:22307294

  20. Activation of rat intestinal mucosal mast cells by fat absorption

    PubMed Central

    Sakata, Yasuhisa; Yang, Qing; Li, Xiaoming; Xu, Min; Yoder, Stephanie; Langhans, Wolfgang; Tso, Patrick

    2012-01-01

    Previous studies have linked certain types of gut mucosal immune cells with fat intake. We determined whether fat absorption activates intestinal mucosal mast cells (MMC), a key component of the gut mucosal immune system. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated, and the intraduodenal (i.d.) tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic concentrations of histamine, rat MMC protease II (RMCPII), a specific marker of rat intestinal MMC degranulation, and prostaglandin D2 (PGD2) were measured by ELISA. Intestinal MMC degranulation was visualized by immunofluorescent microscopy of jejunum sections taken at 1 h after Liposyn II gavage. Intraduodenal bolus infusion of Liposyn II 20% (4.4 kcal/3 ml) induced approximately a onefold increase in lymphatic histamine and PGD2, ?20-fold increase in lymphatic RMCPII, but only onefold increase in peripheral serum RMCPII concentrations. Release of RMCPII into lymph increased dose dependently with the amount of lipid fed. In addition, i.d. infusion of long-chain triacylglycerol trilinolein (C18:2 n-6, the major composite in Liposyn II) significantly increased the lymphatic RMCPII concentration, whereas medium-chain triacylglycerol tricaprylin (C8:0) did not alter lymph RMCPII secretion. Immunohistochemistry image revealed the degranulation of MMC into lamina propria after lipid feeding. These novel findings indicate that intestinal MMC are activated and degranulate to release MMC mediators to the circulation during fat absorption. This action of fatty acid is dose and chain length dependent. PMID:22461027

  1. Amalgam tattoo mimicking mucosal melanoma: a diagnostic dilemma revisited.

    PubMed

    Lundin, K; Schmidt, G; Bonde, C

    2013-01-01

    Mucosal melanoma of the oral cavity is a rare but highly aggressive neoplasm. However, the clinicians need to be aware of the other and more frequent etiologies of intraoral pigmentation, such as amalgam tattoos. As amalgam has been extensively used for dental restorations and can cause pigmentations in the oral mucosa, this is a differential diagnosis not to be forgotten. We describe the characteristics of these two phenomena and present a case vignette illustrating the differential diagnostic issues. Other causes of intraoral pigmentation are summarized. PMID:23533829

  2. The Impact of the Gut Microbiome on Mucosal Inflammation

    PubMed Central

    Strober, Warren

    2013-01-01

    In the last 10 years it has become increasingly apparent that the gut microbiome has profound effects on the immune system to which it is juxtaposed, the mucosal immune system. Here I explore recent studies in which the effects of the microbiota expand or facilitate anti-inflammatory or regulatory immunologic machinery or which favor development of pro-inflammatory immunologic machinery in this system. I then focus on how these opposing processes play out in inflammatory bowel disease, a disease in which normal immune homeostasis is disturbed and inflammation takes hold. PMID:23957963

  3. Mucosal lichenoid drug reaction associated with glimepiride: a case report.

    PubMed

    Hammami, S; Ksouda, K; Affes, H; Sahnoun, Z; Zeghal, K

    2015-06-01

    We report the case of a 52-year-old man with type 2 diabetes, who developed severe mucosal erosions of the tongue, glans penis and perianal area, induced by glimepiride. A tissue biopsy was performed and revealed the characteristics of lichen planus (LP). The improvement of the patient's condition after withdrawal of glimepiride added to recurrence of the lesions when medication was reintroduced confirmed that the second generation anti-diabetic was the causative agent. To the best of our knowledge, this has not been reported previously. PMID:26166659

  4. Endoscopic mucosal resection in the upper gastrointestinal tract

    PubMed Central

    Ahmadi, Anis; Draganov, Peter

    2008-01-01

    Endoscopic mucosal resection (EMR) is a technique used to locally excise lesions confined to the mucosa. Its main role is the treatment of advanced dysplasia and early gastrointestinal cancers. EMR was originally described as a therapy for early gastric cancer. Recently its use has expanded as a therapeutic option for ampullary masses, colorectal cancer, and large colorectal polyps. In the Western world, the predominant indication for EMR in the upper gastrointestinal tract is the staging and treatment of advance dysplasia and early neoplasia in Barrett’s esophagus. This review will describe the basis, indications, techniques, and complications of EMR, and its role in the management of Barrett’s esophagus. PMID:18395896

  5. Recombinant lactic acid bacteria as mucosal biotherapeutic agents.

    PubMed

    Daniel, Catherine; Roussel, Yvonne; Kleerebezem, Michiel; Pot, Bruno

    2011-10-01

    The safety status of lactic acid bacteria (LAB) and their capacity to survive the passage through the gastrointestinal tract (GI tract) have rendered them excellent candidates for the production of therapeutic proteins and their delivery in situ to the GI tract. During the past two decades, major health benefits of mucosally administered recombinant LAB have been successfully demonstrated, predominantly using animal models. However, the field has recently moved into the era of human clinical trials. In this review, we provide a timely update on the recent important advances made in this field, and outline the potential of recombinant LAB as therapeutic tools for their safe and efficient use in human health. PMID:21665301

  6. The Role of Intestinal Microbiota in the Development and Severity of Chemotherapy-Induced Mucositis

    PubMed Central

    van Vliet, Michel J.; Harmsen, Hermie J. M.; de Bont, Eveline S. J. M.; Tissing, Wim J. E.

    2010-01-01

    Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of radiotherapy and chemotherapy treatment. Clinically, mucositis is associated with pain, bacteremia, and malnutrition. Furthermore, mucositis is a frequent reason to postpone chemotherapy treatment, ultimately leading towards a higher mortality in cancer patients. According to the model introduced by Sonis, both inflammation and apoptosis of the mucosal barrier result in its discontinuity, thereby promoting bacterial translocation. According to this five-phase model, the intestinal microbiota plays no role in the pathophysiology of mucositis. However, research has implicated a prominent role for the commensal intestinal microbiota in the development of several inflammatory diseases like inflammatory bowel disease, pouchitis, and radiotherapy-induced diarrhea. Furthermore, chemotherapeutics have a detrimental effect on the intestinal microbial composition (strongly decreasing the numbers of anaerobic bacteria), coinciding in time with the development of chemotherapy-induced mucositis. We hypothesize that the commensal intestinal microbiota might play a pivotal role in chemotherapy-induced mucositis. In this review, we propose and discuss five pathways in the development of mucositis that are potentially influenced by the commensal intestinal microbiota: 1) the inflammatory process and oxidative stress, 2) intestinal permeability, 3) the composition of the mucus layer, 4) the resistance to harmful stimuli and epithelial repair mechanisms, and 5) the activation and release of immune effector molecules. Via these pathways, the commensal intestinal microbiota might influence all phases in the Sonis model of the pathogenesis of mucositis. Further research is needed to show the clinical relevance of restoring dysbiosis, thereby possibly decreasing the degree of intestinal mucositis. PMID:20523891

  7. Effects of leaf extracts on glutathione reductase expression, hydrogen peroxide and glutathione contents in the aquatic macrophyte Ceratophyllum demersum

    Microsoft Academic Search

    Sheku Kamara; Stephan Pflugmacher

    2008-01-01

    .  Due to senescence and anthropogenic activities, leaves fall into aquatic systems or in their proximity. They decompose and\\u000a release chemicals that may influence aquatic biota by imposing oxidative stress. It is known that allochthonous leaf litter\\u000a alone contributes 30% of total dissolved organic carbon (DOC) in streams. We investigated changes in H2O2 and glutathione contents in the coontail, Ceratophyllum demersum,

  8. Effect of ovariectomy and sex hormone replacement on glutathione and glutathione-related enzymes in rat hepatocarcinogenesis.

    PubMed

    Hambali, Z; Ngah, W Z; Wahid, S A; Kadir, K A

    1995-01-01

    The effects of ovariectomy and hormone replacement in control and carcinogen treated female rats were investigated by measuring whole blood and liver glutathione (WGSH, HGSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GRx) and histological evaluation. Hepatocarcinogenesis was induced by diethylnitrosamine and 2-acetylaminofluorene. In control rats not receiving carcinogen, ovariectomy significantly increased the GST and GRx activities. Replacement with either estrogen or progesterone reduced the GST activities to below intact female values whereas replacement of both hormones together brought the GST activities to that of intact females. GRx activities were brought to intact female values by replacement with estrogen or progesterone, either singly or in combination. Neither ovariectomy nor sex hormone/s replacement influenced the levels of WGSH, HGSH and GPx activities. Carcinogen administration to intact rats increased all the parameters measured. Ovariectomized rats treated with carcinogen showed lower GPx and GRx activities at 2 mths. However, replacement with either progesterone or combined estrogen and progesterone increased GPx and GRx activities to original values. On the other hand GST and GPx activities in ovariectomized rats which had carcinogen treatment were lower than intact rats after 5 mths. Replacement with hormones either singly or both brought GST and GPx activities up to intact rat levels receiving carcinogen. The levels of WGSH, HGSH and GRx activities (5 mths) in carcinogen treated rats were not influenced by ovariectomy and/or hormone/s replacement. The results from this study suggested that ovariectomy reduced the severity of hepatocarcinogenesis which was restored by sex hormone/s replacement. PMID:7603748

  9. Unveiling the roles of the glutathione redox system in vivo by analyzing genetically modified mice

    PubMed Central

    Fujii, Junichi; Ito, Jun-itsu; Zhang, Xuhong; Kurahashi, Toshihiro

    2011-01-01

    Redox status affects various cellular activities, such as proliferation, differentiation, and death. Recent studies suggest pivotal roles of reactive oxygen species not only in pathogenesis under oxidative insult but also in intracellular signal transduction. Glutathione is present in several millimolar concentrations in the cytoplasm and has multiple roles in the regulation of cellular homeostasis. Two enzymes, ?-glutamylcysteine synthetase and glutathione synthetase, constitute the de novo synthesis machinery, while glutathione reductase is involved in the recycling of oxidized glutathione. Multidrug resistant proteins and some other transporters are responsible for exporting oxidized glutathione, glutathione conjugates, and S-nitrosoglutathione. In addition to antioxidation, glutathione is more positively involved in cellular activity via its sulfhydryl moiety of a molecule. Animals in which genes responsible for glutathione metabolism are genetically modified can be used as beneficial and reliable models to elucidate roles of glutathione in vivo. This review article overviews recent progress in works related to genetically modified rodents and advances in the elucidation of glutathione-mediated reactions. PMID:21980221

  10. Synthesis of Glutathione in Leaves of Transgenic Poplar Overexpressing [gamma]-Glutamylcysteine Synthetase.

    PubMed Central

    Noctor, G.; Strohm, M.; Jouanin, L.; Kunert, K. J.; Foyer, C. H.; Rennenberg, H.

    1996-01-01

    Internode stem fragments of the poplar hybrid Populus tremula x Populus alba were transformed with a bacterial gene (gshl) for [gamma]-glutamylcysteine synthetase ([gamma]-ECS) targeted to the cytosol. Lines overexpressing [gamma]-ECS were identified by northern analysis, and the transformant with the highest enzyme activity was used to investigate the control of glutathione synthesis. Whereas foliar [gamma]-ECS activity was below the limit of detection in untransformed plants, activities of up to 8.7 nmol mg-1 protein min-1 were found in the transformant, in which the foliar contents of [gamma]-glutamylcysteine ([gamma]-EC) and glutathione were increased approximately 10- and 3-fold, respectively, without affecting either the reduction state of the glutathione pool or the foliar cysteine content. A supply of exogenous cysteine to leaf discs increased the glutathione content from both transformed and untransformed poplars, and caused the [gamma]-EC content of the transformant discs to increase still further. The following conclusions are drawn: (a) the native [gamma]-ECS of untransformed poplars exists in quantities that are limiting for foliar glutathione synthesis; (b) foliar glutathione synthesis in untransformed poplars is limited by cysteine availability; (c) in the transformant interactions between glutathione synthesis and cysteine synthesis operate to sustain the increased formation of [gamma]-EC and glutathione; and (d) the foliar glutathione content of the transformant is restricted by cysteine availability and by the activity of glutathione synthetase. PMID:12226433

  11. Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells.

    PubMed

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

    2013-11-22

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

  12. Exposure to cadmium changes the content of glutathione in maize seedlings

    SciTech Connect

    Rauser, W.E.

    1987-04-01

    Glutathione may be involved in the biosynthesis of Cd-binding peptides known as phytochelatins. Five-day old maize seedlings in hydroponic culture were exposed to 3 ..mu..M CdSO/sub 4/ for 2, 6 and 12 hours and 1, 2 and 3 days. Total glutathione (glutathione + glutathione disulfide) in roots and shoots was measured enzymatically. Exposure to Cd for 12 hours or longer reduced root elongation growth. Shoots contained more glutathione than did roots. Within 2 hours of exposure to Cd the glutathione content declined by 47% of control and stayed low for a day. Shoot glutathione decreased gradually and less markedly (by 34% in 24 hours). Following the decline in the first day the glutathione per seedling increased with time in the presence of Cd. Cadmium-binding peptide in roots increased during the recovery phase. If glutathione is a substrate for Cd-binding peptide synthesis, such a use accounts for only part of the decline in root glutathione observed during the first day.

  13. Standardized ileal digestibility of amino acids in eight genotypes of soft winter wheat fed to growing pigs.

    PubMed

    Rosenfelder, P; Mosenthin, R; Spindler, H K; Jørgensen, H; Bach Knudsen, K E; Sauer, N; Htoo, J K; Eklund, M

    2015-03-01

    A study with growing pigs was conducted to determine the chemical composition and standardized ileal digestibility (SID) of CP and AA of 8 wheat genotypes that have recently been added to the German Descriptive Variety List. These genotypes included Tabasco, KWS Erasmus, Tobak, Skalmeje, Mulan, Event, Tommi, and Adler. The 8 genotypes were grown under identical environmental conditions on the same site, and they were harvested and processed under the same conditions. Nine barrows with an initial BW of 32 ± 2 kg were surgically fitted with simple ileal T-cannulas and allotted to a row-column design with 9 pigs and 8 periods of 6 d each. Wheat was the sole dietary source of CP and AA. Among the 8 wheat genotypes, contents of CP ranged from 10.9 to 13.3% (as-fed basis), whereas contents of total nonstarch polysaccharides ranged from 8.0 to 9.4% (as-fed basis). The SID of CP in the 8 genotypes ranged from 83 to 87%, with greatest ( = 0.01) values for Event and lowest ( = 0.01) for all other wheat genotypes. Intermediate SID of CP values were obtained for Adler and KWS Erasmus. For Lys, greater ( < 0.05) SID was observed in Adler (73%) and KWS Erasmus (74%) in comparison to Tommi, Tobak, and Mulan (69%). Adler had greater SID of Met (88%; = 0.01) when compared to Tabasco (86%); Tobak, Skalmeje, and Mulan (85%); and Tommi (84%). Among the 8 wheat genotypes, standardized ileal digestible content (cSID) of CP followed total CP content and ranged from 9.1 to 11.3% (as-fed basis). Standardized ileal digestible content of both CP and AA were greater ( < 0.001) in Adler compared to all other genotypes. For most AA, Tabasco had the lowest ( < 0.001; except for His, Trp, Asp, and Cys) cSID values of all wheat genotypes. The cSID of CP decreased ( < 0.001) as the starch content in the 8 wheat genotypes increased, but cSID of CP increased ( < 0.001) as the CP content in the 8 genotypes increased. Because SID and cSID of CP and most AA increased ( < 0.05) with lower test weight and falling number, these variables may aid to predict SID and cSID in wheat batches, whereas other nutrients such as fiber fractions are not suitable due to low variation among the 8 genotypes. The present study provides a comprehensive database on nutritional composition and SID of CP and AA of 8 wheat genotypes grown under identical conditions. Because the SID values in these genotypes are lower when compared to literature data, digestibility values in actual feed tables for wheat may overestimate their protein values and need to be updated. PMID:26020890

  14. Apparent selective bile acid malabsorption as a consequence of ileal exclusion: effects on bile acid, cholesterol, and lipoprotein metabolism.

    PubMed Central

    Akerlund, J E; Björkhem, I; Angelin, B; Liljeqvist, L; Einarsson, K

    1994-01-01

    A new model has been developed to characterise the effect of a standardised ileal exclusion on bile acid, cholesterol, and lipoprotein metabolism in humans. Twelve patients treated by colectomy and ileostomy for ulcerative colitis were studied on two occasions: firstly with a conventional ileostomy and then three months afterwards with an ileal pouch operation with an ileoanal anastomosis and a protective loop ileostomy, excluding on average 95 cm of the distal ileum. The ileostomy contents were collected during 96 hours and the excretion of bile acids and cholesterol was determined using gas chromatography-mass spectrometry. Fasting blood and duodenal bile samples were collected on two consecutive days. After the exclusion of the distal ileum, both cholic and chenodeoxycholic acid excretion in the ileostomy effluent increased four to five times without any change in cholesterol excretion. Serum concentrations of lathosterol (a marker of cholesterol biosynthesis) and 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) were increased several fold. Plasma concentrations of total VLDL triglycerides were also increased whereas the concentrations of total and LDL cholesterol, and apolipoprotein B were decreased. There were no changes in biliary lipid composition or cholesterol saturation of bile. The results show that the exclusion of about 95 cm of distal ileum causes malabsorption of bile acids but apparently not of cholesterol. The bile acid malabsorption leads to increased synthesis of both bile acids and cholesterol in the liver. It is suggested that bile acids can regulate cholesterol synthesis by a mechanism independent of the effect of bile acids on cholesterol absorption. The enhanced demand for cholesterol also leads to a decrease in plasma LDL cholesterol and apolipoprotein B concentrations. The malabsorption of bile acids did not affect biliary lipid composition or cholesterol saturations of VLDL triglycerides. PMID:7926917

  15. Protein carbonyl formation on mucosal proteins in vitro and in dextran sulfate-induced colitis

    Microsoft Academic Search

    Anneke C Blackburn; William F Doe; Gary D Buffinton

    1999-01-01

    Reactive oxygen and nitrogen species have been implicated as mediators of mucosal injury in inflammatory bowel disease, but few studies have investigated protein oxidation in the inflamed mucosa. In this study, protein carbonyl formation on colonic mucosal proteins from mice was investigated following in vitro exposure of homogenates to iron\\/ascorbate, hydrogen peroxide, hypochloric acid (HOCl), or nitric oxide (NO). Total

  16. Wild chamomile ( Matricaria recutita L.) mouthwashes in methotrexate-induced oral mucositis

    Microsoft Academic Search

    E. E. Mazokopakis; G. E. Vrentzos; J. A. Papadakis; D. E. Babalis; E. S. Ganotakis

    2005-01-01

    Oral mucositis is a known complication of methotrexate (MTX) therapy, but a single efficacious intervention or agent for prophylaxis or management of this side effect has not yet been identified. We report a case of MTX-induced oral mucositis in a patient with rheumatoid arthritis, who was successfully treated with Wild chamomile mouthwashes.

  17. Circumferential endoscopic mucosal resection in the swine esophagus assisted by a cap attachment

    Microsoft Academic Search

    Jan P. Kamler; Richardo Borsatto; Kenneth F. Binmoeller

    2002-01-01

    Background: The feasibility and safety of piecemeal, circumferential endoscopic mucosal resection of the distal esophagus are unknown. This study assessed this procedure in a porcine model. Methods: Different techniques of endoscopic mucosal resection were tested in Phase I of the study in two animals. During Phase II, 6 pigs underwent piecemeal cap-assisted EMR of the distal esophagus. The mucosa of

  18. The role of TLRs, NLRs, and RLRs in mucosal innate immunity and homeostasis

    Microsoft Academic Search

    E C Lavelle; C Murphy; L A J O’Neill; E M Creagh

    2010-01-01

    The mucosal surfaces of the gastrointestinal tract are continually exposed to an enormous antigenic load of microbial and dietary origin, yet homeostasis is maintained. Pattern recognition molecules (PRMs) have a key role in maintaining the integrity of the epithelial barrier and in promoting maturation of the mucosal immune system. Commensal bacteria modulate the expression of a broad range of genes

  19. Influencing mucosal homeostasis and immune responsiveness: The impact of nutrition and pharmaceuticals

    Microsoft Academic Search

    Belinda van't Land; Marcel A. Schijf; Rocio Martin; Johan Garssen; Grada M. van Bleek

    2011-01-01

    Both nutrition and orally ingested drugs pass the gastrointestinal mucosa and may affect the balance between the mucosal immune system and microbial community herein, i.e. affecting composition of the microbial community as well as the status of local immune system that controls microbial composition and maintains mucosal integrity. Numerous ways are known by which the microbial community stimulates mammalian host's

  20. Antigen targeting to M cells for enhancing the efficacy of mucosal vaccines

    PubMed Central

    Kim, Sae-Hae; Jang, Yong-Suk

    2014-01-01

    Vaccination is one of the most successful applications of immunology and for a long time has depended on parenteral administration protocols. However, recent studies have pointed to the promise of mucosal vaccination because of its ease, economy and efficiency in inducing an immune response not only systemically, but also in the mucosal compartment where many pathogenic infections are initiated. However, successful mucosal vaccination requires the help of an adjuvant for the efficient delivery of vaccine material into the mucosa and the breaking of the tolerogenic environment, especially in oral mucosal immunization. Given that M cells are the main gateway to take up luminal antigens and initiate antigen-specific immune responses, understanding the role and characteristics of M cells is crucial for the development of successful mucosal vaccines. Especially, particular interest has been focused on the regulation of the tolerogenic mucosal microenvironment and the introduction of the luminal antigen into the lymphoid organ by exploiting the molecules of M cells. Here, we review the characteristics of M cells and the immune regulatory factors in mucosa that can be exploited for mucosal vaccine delivery and mucosal immune regulation. PMID:24626171

  1. Local antimicrobial therapy of oral mucositis in paediatric patients undergoing bone marrow transplantation

    Microsoft Academic Search

    E. Bondi; C. Baroni; A. Prete; M. Gatti; A. Carrassi; G. Lodi; S. R. Porters

    1997-01-01

    The present investigation has examined the clinical benefits of tobramycin, polymyxin E and amphotericin therapy in the management of oral mucositis in children undergoing chemotherapy prior to bone marrow transplantation. Tobramycin, polymyxin E, and amphotericin reduced the degree of oral mucositis more than conventional therapy of diphenhydramine, Maalox, and local analgesic. While there was a statistically significant fall in the

  2. Characterization of mucoadhesive microspheres for the induction of mucosal and systemic immune responses

    Microsoft Academic Search

    Jun Kunisawa; Akiko Okudaira; Yasuo Tsutusmi; Ichiro Takahashi; Tsuyoshi Nakanishi; Hiroshi Kiyono; Tadanori Mayumi

    2000-01-01

    In the present study, mucoadhesive polymer-dispersed microspheres (MS) were examined as a potential mucosal vaccine carrier. A major focus of the study was aimed at directly assessing the influence of antigen release and persistence in the mouse small intestine for the induction of mucosal and systemic immune responses. BALB\\/c mice were immunized with various forms of MS containing chicken egg

  3. Etiology and Outcome of Oral Mucosal Lesions in Children on Chemotherapy for Acute Lymphoblastic Leukemia

    Microsoft Academic Search

    DEEPA ANIRUDHAN; SAMEER B AKHSHI; IMMACULATA XESS; SHOBHA BROOR; LS ARYA

    Microbiological cultures were taken from oral cavity and blood in 100 mucositis episodes in 70 children with acute lymphoblastic leukemia (ALL). Oral mucositis was commonest in neutropenic children during induction chemotherapy. Fungal organisms (n=39) were commonest isolate from mucosa followed by bacteria (n=28). Isolation of organism from oral cavity had no association with those isolated from blood. Herpes serology was

  4. Comparison of systemic and mucosal vaccination: impact on intravenous and rectal SIV challenge

    Microsoft Academic Search

    D L Bolton; K Song; R L Wilson; P A Kozlowski; G D Tomaras; B F Keele; R V Lovingood; S Rao; M Roederer

    2012-01-01

    Mucosal tissues are the primary route of transmission for most respiratory and sexually transmitted diseases, including human immunodeficiency virus. We aimed to generate strong mucosal immune responses to simian immunodeficiency virus (SIV) in rhesus macaques by targeting recombinant adenovirus serotype 5 (rAd5) to the lung. The immunogenicity and efficacy of aerosol (AE) vaccination was compared with intramuscular (IM) delivery in

  5. Structure and mucosal adjuvanticity of cholera and Escherichia coli heat-labile enterotoxins

    Microsoft Academic Search

    Rino Rappuoli; Mariagrazia Pizza; Gill Douce; Gordon Dougan

    1999-01-01

    Escherichia coli heat-labile enterotoxin and cholera toxin are potent mucosal immunogens and adjuvants in animal models. Non-toxic mutants retaining adjuvant activity are useful tools to dissect the mechanism of mucosal adjuvanticity and promising candidates for development of human vaccines and immunotherapy. Clinical trials are expected to proceed in the near future.

  6. Use of inactivated E.Coli enterotoxins to enhance respiratory mucosal adjuvanticity during vaccination in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to augment responses to respiratory vaccines in swine, various adjuvants were intranasally co-administered with an antigen to pigs. Detoxified E. coli enterotoxins LTK63 and LTR72 enhanced mucosal and systemic immunity to the model peptide, exhibiting their efficacy as mucosal adjuvants for...

  7. A lumped mucosal wave model of the vocal folds revisited: Recent extensions and oscillation hysteresis

    E-print Network

    A lumped mucosal wave model of the vocal folds revisited: Recent extensions and oscillation an updated version of a lumped mucosal wave model of the vocal fold oscilla- tion during phonation. Threshold against pressure data collected from a mechanical rep- lica of the vocal folds, and oral airflow data

  8. Intestinal epithelial barrier and mucosal immunity Coordinator: J.C. Sirard

    E-print Network

    Paris-Sud XI, Université de

    1 MAR Intestinal epithelial barrier and mucosal immunity Coordinator: J.C. Sirard deviation for "beneficial" antigens (so-called "oral tolerance") on one hand and mechanisms which defend of the ongoing colonization prior to mucosal invasion. Recent observations have shown that mammalian genomes code

  9. Risk factors for ulcerative oral mucositis in cancer patients: unanswered questions

    Microsoft Academic Search

    Andrei Barasch; Douglas E Peterson

    2003-01-01

    A multitude of laboratory and clinical research studies of ulcerative oral mucositis induced by cytotoxic cancer therapies have been reported during the past decade. However, a comprehensive understanding of oral mucositis pathogenesis, together with a clear definition of risk factors for development and severity of the lesion, remain under investigation. The literature presents sometimes divergent data regarding these issues, which

  10. Prevention and treatment of chemotherapy- and radiotherapy-induced oral mucositis: a review

    Microsoft Academic Search

    P. Plevová

    1999-01-01

    Oral mucositis is a distressing toxic effect of systemic chemotherapy with many commonly utilized drugs and of head and neck irradiation in patients with cancer. The agents and methods that have been used and studied in chemotherapy- and radiotherapy-induced oral mucositis, their mechanisms of action, and the current knowledge of their efficiency to reduce the incidence, severity or shorten the

  11. Intra-operative gut mucosal hypoperfusion is associated with increased post-operative complications and cost

    Microsoft Academic Search

    M. G. Mythen; A. R. Webb

    1994-01-01

    Objectives: To determine CO and gastric mucosal perfusion in patients during elective major sur- gery; to seek a relationship with subsequent outcome. Design: Prospective descriptive study. Setting: University hospital. Patients: 51 patients undergoing elective major surgery of an anticipated duration of greater than 2 h who were at risk of developing gut mucosal hypoperfusion and post- operative organ failure. Measurements

  12. The mucosal surfaces of the mammalian skin, airways, reproductive tract and intestine are in direct contact

    E-print Network

    Cai, Long

    The mucosal surfaces of the mammalian skin, airways, reproductive tract and intestine are in direct system. This challenge is arguably most acute in the intestinal tract, the largest mucosal surface of the human body. The intestinal surface covers an area of approximately 100 m2 and is lined by a single layer

  13. The common mucosal immune system for the reproductive tract: basic principles applied toward an AIDS vaccine

    Microsoft Academic Search

    Hiroshi Kiyono; Christopher J. Miller; Yichen Lu; Thomas Lehner; Martin Cranage; Yung T. Huang; Shigetada Kawabata; Marta Marthas; Bryan Roberts; John G. Nedrud; Michael E. Lamm; Lesley Bergmeier; Roger Brookes; Louisa Tao; Jerry R. McGhee

    1995-01-01

    The concept of the Collaborative Mucosal Immunization Research Group for AIDS (CMIG) was originally conceived by the AIDS Vaccine Branch, National Institute of Allergy and Infectious Diseases (NIAID) in order to provide support for a cooperative research environment for the development of mucosal immunity to AIDS. We have purposely organized five groups of investigators at five different locations to determine

  14. External Dacryocystorhinostomy with and Without Suturing the Posterior Mucosal Flaps

    PubMed Central

    Kaçaniku, Gazmend; Begolli, Ilir

    2014-01-01

    ABSTRACT Purpose: To evaluate the outcome of the external dacryocystorhinostomy with and without suturing the posterior mucosal flaps. Methods: This study included 106 patients with lacrimal drainage system disorders who underwent the external dacryocystorhinostomy. Fifty four patients (Group A) underwent external dacryocystorhinostomy with suturing anterior and posterior flaps of the lacrimal sac and nasal mucosa, and the results obtained were compared with those of another series of 52 patients (Group B) where dacryocystorhinostomy was performed with suturing only the anterior flaps, whereas posterior mucosal flaps were excised. Results: The success rate was evaluated by lacrimal patency to irrigation and relief of epiphora. Patency achieved in groups A and B was 94.4% and 96.2%, respectively. There was no statistically significant difference in success rate between the groups. Conclusion: Our study suggests that external dacryocystorhinostomy with suturing anterior and posterior flaps have no advantage over dacryocystorhinostomy with suturing only anterior flaps. Anastomosis by suturing only anterior flaps and excision of the posterior flaps is easier to perform and may improve the success rate of external dacryocystorhinostomy. PMID:24783915

  15. Effects of spaceflight on the proliferation of jejunal mucosal cells

    NASA Technical Reports Server (NTRS)

    Phillips, Robert W.; Moeller, C. L.; Sawyer, Heywood R.; Smirnov, K. L.

    1991-01-01

    The purpose of this project was to test the hypothesis that the generalized, whole body decrease in synthetic activity due to microgravity conditions encountered during spaceflight would be demonstrable in cells and tissues characterized by a rapid rate of turnover. Jejunal mucosal cells were chosen as a model since these cells are among the most rapidly proliferating in the body. Accordingly, the percentage of mitotic cells present in the crypts of Lieberkuhn in each of 5 rats flown on the COSMOS 2044 mission were compared to the percentage of mitotic cells present in the crypts in rats included in each of 3 ground control groups (i.e., vivarium, synchronous and caudal-elevated). No significant difference (p greater than .05) was detected in mitotic indices between the flight and vivarium group. Although the ability of jejunal mucosal cells to divide by mitosis was not impaired in flight group, there was, however, a reduction in the length of villi and depth of crypts. The concommitant reduction in villus length and crypth depth in the flight group probably reflects changes in connective tissue components within the core of villi.

  16. Mucosal Adjuvants for Influenza Virus-Like Particle Vaccine

    PubMed Central

    Ko, Eun-Ju; Kwon, Young-Man; Joo, Kyoung Hwan; Compans, Richard W.

    2013-01-01

    Abstract To find an effective mucosal adjuvant for influenza virus-like particles (VLPs), we compared the effects of known adjuvants Alum, CpG DNA, monophosphoryl lipid A (MPL), poly IC, gardiquimod, and cholera toxin (CT). Mice that were intranasally immunized with Alum, CpG, MPL, and CT adjuvanted VLPs showed higher levels of antibodies in both sera and mucosa. Hemagglutination inhibition and virus neutralizing activities were enhanced in groups adjuvanted with Alum, MPL, or CT. Influenza virus specific long-lived cells secreting IgG and IgA antibodies were found at high levels both in bone marrow and spleen in the Alum, CpG and CT adjuvanted groups. A similar level of protection was observed among different adjuvanted groups, except the CT adjuvant that showed a higher efficacy in lowering lung viral loads after challenge. Alum and CT adjuvants differentially increased influenza VLP-mediated activation of dendritic cells and splenocytes in vitro, supporting the in vivo pattern of antibody isotypes and cytokine production. These results suggest that Alum, MPL, or CpG adjuvants, which have been tested clinically, can be developed as an effective mucosal adjuvant for influenza VLP vaccines. PMID:24236855

  17. Intestinal mucosal defense system, Part 1. Consensus recommendations for immunonutrients.

    PubMed

    Neu, Josef; Mihatsch, Walter A; Zegarra, Jaime; Supapannachart, Sarayut; Ding, Zong-Yi; Murguía-Peniche, Teresa

    2013-03-01

    When microbial communities colonize in the developing intestinal tract after birth, microorganisms interact with specific apical surface receptors on the enterocytes. This interaction triggers a response that prevents overexpression of inflammatory cytokines, thus providing protection from pathogen-induced mucosal damage. Multiple immune modulatory factors in human milk and innate humoral factors also control inflammatory responses, providing additional protective effects. Our understanding of the role of the luminal microbial communities or microbiota is growing rapidly as novel technologies provide new insights into their taxonomy, function during early development, and impact on life-long health. Multiple studies have evaluated the effects of the specific nutrients, glutamine, arginine, nucleotides, polyunsaturated fatty acids, and lactoferrin, on disease outcomes in premature infants. These studies support a role for nutrients to modulate host defense mechanisms in premature infants, to develop normal digestive function, to protect from bacterial translocation, and to preserve mucosal barrier integrity. These effects are clearly important. However, not enough is yet known to design specific clinical care practices that support a healthy microbiota. PMID:23445849

  18. Cyclic GMP-AMP Displays Mucosal Adjuvant Activity in Mice

    PubMed Central

    Škrnjug, Ivana

    2014-01-01

    The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity – a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines. PMID:25295996

  19. Cutaneous and Mucosal Aphthosis during Temsirolimus Therapy for Advanced Renal Cell Carcinoma: Review of Cutaneous and Mucosal Side Effects of mTOR Inhibitors

    Microsoft Academic Search

    A. De Masson; N. Fouchard; L. Méry-Bossard; J. N. Dauendorffer

    2011-01-01

    Temsirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is a new targeted therapy used in advanced renal cell carcinoma and mantle cell lymphoma and is currently tested in several other human tumors. It induces several cutaneous and mucosal side effects, including painful, dose-limiting stomatitis. We report the unusual case of a 77-year-old man who developed severe mucosal, scrotal

  20. Ex vivo characterization of particle transport in mucus secretions coating freshly excised mucosal tissues

    PubMed Central

    Ensign, Laura M.; Henning, Andreas; Schneider, Craig S.; Maisel, Katharina; Wang, Ying-Ying; Porosoff, Marc D.; Cone, Richard; Hanes, Justin

    2013-01-01

    Sustained drug delivery to mucosal surfaces has the potential to improve the effectiveness of prophylactic and therapeutic treatments for numerous diseases and conditions, including inflammatory bowel disease, sexually transmitted diseases, cystic fibrosis, glaucoma, dry eye and various cancers. Sustained delivery systems such as nanoparticles can be useful for mucosal delivery, but recent work suggests they should penetrate the rapidly cleared mucus barrier that overlies all mucosal epithelia to achieve uniform distribution on epithelial surfaces and enhanced residence time. Thus, it is important to evaluate mucus-penetrating ability of nano-sized delivery systems in preclinical animal studies, and for administration to humans. We describe a simple ex vivo method to visualize and quantify nanoparticle transport in mucus on fresh mucosal tissues. Using this method in murine models, we observed variations in the mucus mesh at various anatomical locations, as well as cyclical variations that may have implications for mucosal delivery. PMID:23617606