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Sample records for human gastrointestinal epithelium

  1. Effects of wheat germ agglutinin on human gastrointestinal epithelium: Insights from an experimental model of immune/epithelial cell interaction

    International Nuclear Information System (INIS)

    Pellegrina, Chiara Dalla; Perbellini, Omar; Scupoli, Maria Teresa; Tomelleri, Carlo; Zanetti, Chiara; Zoccatelli, Gianni; Fusi, Marina; Peruffo, Angelo; Rizzi, Corrado; Chignola, Roberto

    2009-01-01

    Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed, among many others, by human gastrointestinal epithelial and immune cells. WGA is a toxic compound and an anti-nutritional factor, but recent works have shown that it may have potential as an anti-tumor drug and as a carrier for oral drugs. To quantitate the toxicity threshold for WGA on normal epithelial cells we previously investigated the effects of the lectin on differentiated Caco2 cells, and showed that in the micromolar range of concentrations WGA could alter the integrity of the epithelium layer and increase its permeability to both mannitol and dextran. WGA was shown to be uptaken by Caco2 cells and only ∼ 0.1% molecules were observed to cross the epithelium layer by transcytosis. Here we show that at nanomolar concentrations WGA is unexpectedly bioactive on immune cells. The supernatants of WGA-stimulated peripheral blood mononuclear cells (PBMC) can alter the integrity of the epithelium layer when administered to the basolateral side of differentiated Caco2 cells and the effects can be partially inhibited by monoclonal antibodies against IL1, IL6 and IL8. At nanomolar concentrations WGA stimulates the synthesis of pro-inflammatory cytokines and thus the biological activity of WGA should be reconsidered by taking into account the effects of WGA on the immune system at the gastrointestinal interface. These results shed new light onto the molecular mechanisms underlying the onset of gastrointestinal disorders observed in vivo upon dietary intake of wheat-based foods.

  2. Epithelium

    Science.gov (United States)

    The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make ... Kierszenbaum AL, Tres LL. Epithelium. In: Kierszenbaum AL, Tres LL, ... to Pathology . 4th ed. Philadelphia, PA: Elsevier Saunders; ...

  3. In vivo models of human airway epithelium repair and regeneration

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    C. Coraux

    2005-12-01

    Full Text Available Despite an efficient defence system, the airway surface epithelium, in permanent contact with the external milieu, is frequently injured by inhaled pollutants, microorganisms and viruses. The response of the airway surface epithelium to an acute injury includes a succession of cellular events varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even to complete denudation of the basement membrane. The epithelium has then to repair and regenerate to restore its functions. The in vivo study of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to reconstitute a functional respiratory epithelium after several weeks. Humanised tracheal xenograft models have been developed in immunodeficient nude and severe combined immunodeficient (SCID mice in order to mimic the natural regeneration process of the human airway epithelium and to analyse the cellular and molecular events involved during the different steps of airway epithelial reconstitution. These models represent very powerful tools for analysing the modulation of the biological functions of the epithelium during its regeneration. They are also very useful for identifying stem/progenitor cells of the human airway epithelium. A better knowledge of the mechanisms involved in airway epithelium regeneration, as well as the characterisation of the epithelial stem and progenitor cells, may pave the way to regenerative therapeutics, allowing the reconstitution of a functional airway epithelium in numerous respiratory diseases, such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and bronchiolitis.

  4. Permeability and ultrastructure of human bladder epithelium

    DEFF Research Database (Denmark)

    Eldrup, J; Thorup, Jørgen Mogens; Nielsen, S L

    1983-01-01

    Leakage of tight junctions as observed with electron microscopy and demonstration of solute transport across bladder epithelium was investigated in 13 patients with different bladder diseases: urinary retention and infection, bladder tumours and interstitial cystitis. The latter group showed...

  5. Human Milk Hyaluronan Enhances Innate Defense of the Intestinal Epithelium*

    Science.gov (United States)

    Hill, David R.; Rho, Hyunjin K.; Kessler, Sean P.; Amin, Ripal; Homer, Craig R.; McDonald, Christine; Cowman, Mary K.; de la Motte, Carol A.

    2013-01-01

    Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human β-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human β-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine Hβ D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn. PMID:23950179

  6. Identification of distinct layers within the stratified squamous epithelium of the adult human true vocal fold.

    Science.gov (United States)

    Dowdall, Jayme R; Sadow, Peter M; Hartnick, Christopher; Vinarsky, Vladimir; Mou, Hongmei; Zhao, Rui; Song, Phillip C; Franco, Ramon A; Rajagopal, Jayaraj

    2015-09-01

    A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Qualitative study with adult human larynges. Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. N/A. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  7. Water permeability in human airway epithelium

    DEFF Research Database (Denmark)

    Pedersen, Peter Steen; Procida, Kristina; Larsen, Per Leganger

    2005-01-01

    Osmotic water permeability (P(f)) was studied in spheroid-shaped human airway epithelia explants derived from nasal polyps by the use of a new improved tissue collection and isolation procedure. The fluid-filled spheroids were lined with a single cell layer with the ciliated apical cell membrane ...

  8. Lactobacillus reuteri Inhibition of Enteropathogenic Escherichia coli Adherence to Human Intestinal Epithelium

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    Alistair eWalsham

    2016-03-01

    Full Text Available Enteropathogenic E. coli (EPEC is a major cause of diarrheal infant death in developing countries, and probiotic bacteria have been shown to provide health benefits in gastrointestinal infections. In this study, we have investigated the influence of the gut symbiont Lactobacillus reuteri on EPEC adherence to the human intestinal epithelium. Different host cell model systems including non-mucus-producing HT-29 and mucus-producing LS174T intestinal epithelial cell lines as well as human small intestinal biopsies were used. Adherence of L. reuteri to HT-29 cells was strain-specific, and the mucus-binding proteins CmbA and MUB increased binding to both HT-29 and LS174T cells. L. reuteri ATCC PTA 6475 and ATCC 53608 significantly inhibited EPEC binding to HT-29 but not LS174T cells. While pre-incubation of LS174T cells with ATCC PTA 6475 did not affect EPEC A/E lesion formation, it increased the size of EPEC microcolonies. ATCC PTA 6475 and ATCC 53608 binding to the mucus layer resulted in decreased EPEC adherence to small intestinal biopsy epithelium. Our findings show that L. reuteri reduction of EPEC adhesion is strain-specific and has the potential to target either the epithelium or the mucus layer, providing further rationale for the selection of probiotic strains.

  9. Lactobacillus reuteri Inhibition of Enteropathogenic Escherichia coli Adherence to Human Intestinal Epithelium.

    Science.gov (United States)

    Walsham, Alistair D S; MacKenzie, Donald A; Cook, Vivienne; Wemyss-Holden, Simon; Hews, Claire L; Juge, Nathalie; Schüller, Stephanie

    2016-01-01

    Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrheal infant death in developing countries, and probiotic bacteria have been shown to provide health benefits in gastrointestinal infections. In this study, we have investigated the influence of the gut symbiont Lactobacillus reuteri on EPEC adherence to the human intestinal epithelium. Different host cell model systems including non-mucus-producing HT-29 and mucus-producing LS174T intestinal epithelial cell lines as well as human small intestinal biopsies were used. Adherence of L. reuteri to HT-29 cells was strain-specific, and the mucus-binding proteins CmbA and MUB increased binding to both HT-29 and LS174T cells. L. reuteri ATCC PTA 6475 and ATCC 53608 significantly inhibited EPEC binding to HT-29 but not LS174T cells. While pre-incubation of LS174T cells with ATCC PTA 6475 did not affect EPEC attaching/effacing (A/E) lesion formation, it increased the size of EPEC microcolonies. ATCC PTA 6475 and ATCC 53608 binding to the mucus layer resulted in decreased EPEC adherence to small intestinal biopsy epithelium. Our findings show that L. reuteri reduction of EPEC adhesion is strain-specific and has the potential to target either the epithelium or the mucus layer, providing further rationale for the selection of probiotic strains.

  10. Zinc uptake in vitro by human retinal pigment epithelium

    International Nuclear Information System (INIS)

    Newsome, D.A.; Rothman, R.J.

    1987-01-01

    Zinc, an essential trace element, is present in unusually high concentrations in the chorioretinal complex relative to most other tissues. Because little has been known about the interactions between the retinal pigment epithelium and free or protein-associated zinc, we studied 65 Zn uptake by human retinal pigment epithelium in vitro. When monolayers were exposed to differing concentrations from 0 to 30 microM 65 Zn in Dulbecco's modified Eagle's medium with 5.4 gm/l glucose at 37 degrees C and 4 degrees C, we observed a temperature-dependent saturable accumulation of the radiolabel. With 15 microM 65 Zn, we saw a biphasic pattern of uptake with a rapid first phase and a slower second phase over 120 min. Uptake of 65 Zn was inhibited by iodacetate and cold, and reduced approximately 50% by the addition of 2% albumin to the labelling medium. Neither ouabain nor 2-deoxyglucose inhibited uptake. Cells previously exposed to 65 Zn retained approximately 70% of accumulated 65 Zn 60 min after being changed to radiolabel-free medium. Following removal of cells from the extracellular matrix adherent to the dish bottom, a variable amount of nonspecific binding of 65 Zn to the residual matrix was demonstrated. These observations are consistent with a facilitated type of transport and demonstrate the ability of human retinal pigment epithelium in vitro to accumulate and retain zinc

  11. Sensory testing of the human gastrointestinal tract.

    NARCIS (Netherlands)

    Brock, C.; Arendt-Nielsen, L.; Wilder-Smith, O.H.G.; Drewes, A.M.

    2009-01-01

    The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and

  12. STUDIES ON HUMAN FALLOPIAN TUBAL EPITHELIUM IN DIFFERENT AGE GROUPS

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    Jayasri

    2016-02-01

    Full Text Available BACKGROUND AND AIMS The “fallopian tubes” (oviducts or uterine tubes are long paired flexuous reproductive organ which transports ova, spermatozoa, zygotes, the pre-implantation morulae and blastocyst. It has major role during reproductive period, but it remains as if vestigial organ before puberty and after menopause. Due to increasing rate of tubal block and infertility, oviducts and their structures gaining importance and have become a subject of research in present days particularly epithelium. The aim of the study is to ascertain any histological difference of tubal epithelium in different age groups and the research work could be utilized for investigation and management of infertility. MATERIALS AND METHODS Seven samples of each group i.e., prereproductive, reproductive & postmenopausal were collected from fresh unembalmed human cadavers received in the department of Anatomy, FAA Medical College, Barpeta, Assam. The slides were prepared using the standard laboratory procedure. Under low and high power objectives the type of cells were observed and epithelial height was measured in the different segments. Stress was given for any significant difference of epithelial height between the different age groups. RESULTS Study revealed that among the groups within the same segment, epithelial height was recorded highest (33.57µm in reproductive group as against the lowest (22.91µm in post-menopausal group. Epithelial structures of the prereproductive and reproductive groups were significantly differed (p<0.01 from the postmenopausal group. CONCLUSIONS From the findings of the present study it can be concluded that: 1. In all the groups fallopian tubal epithelium is of simple columnar type and contains three types of cells. Cells are ciliated, secretory & peg (intercalary cells. 2. In all the groups same type of increasing trend of epithelial height from intramural segment to ampullary segment was recorded. 3. In intergroup comparison of

  13. Effects of silver nanoparticles and ions on a co-culture model for the gastrointestinal epithelium.

    Science.gov (United States)

    Georgantzopoulou, Anastasia; Serchi, Tommaso; Cambier, Sébastien; Leclercq, Céline C; Renaut, Jenny; Shao, Jia; Kruszewski, Marcin; Lentzen, Esther; Grysan, Patrick; Eswara, Santhana; Audinot, Jean-Nicolas; Contal, Servane; Ziebel, Johanna; Guignard, Cédric; Hoffmann, Lucien; Murk, AlberTinka J; Gutleb, Arno C

    2016-02-17

    The increased incorporation of silver nanoparticles (Ag NPs) into consumer products makes the characterization of potential risk for humans and other organisms essential. The oral route is an important uptake route for NPs, therefore the study of the gastrointestinal tract in respect to NP uptake and toxicity is very timely. The aim of the present study was to evaluate the effects of Ag NPs and ions on a Caco-2/TC7:HT29-MTX intestinal co-culture model with mucus secretion, which constitutes an important protective barrier to exogenous agents in vivo and may strongly influence particle uptake. The presence of the mucus layer was confirmed with staining techniques (alcian blue and toluidine blue). Mono and co-cultures of Caco-2/TC7 and HT29-MTX cells were exposed to Ag NPs (Ag 20 and 200 nm) and AgNO3 and viability (alamar blue), ROS induction (DCFH-DA assay) and IL-8 release (ELISA) were measured. The particle agglomeration in the media was evaluated with DLS and the ion release with ultrafiltration and ICP-MS. The effects of the Ag NPs and AgNO3 on cells in co-culture were studied at a proteome level with two-dimensional difference in gel electrophoresis (2D-DIGE) followed by Matrix Assisted Laser Desorption Ionization - Time Of Flight/ Time Of Flight (MALDI-TOF/TOF) mass spectrometry (MS). Intracellular localization was assessed with NanoSIMS and TEM. The presence of mucus layer led to protection against ROS and decrease in IL-8 release. Both Ag 20 and 200 nm NPs were taken up by the cells and Ag NPs 20 nm were mainly localized in organelles with high sulfur content. A dose- and size-dependent increase in IL-8 release was observed with a lack of cytotoxicity and oxidative stress. Sixty one differentially abundant proteins were identified involved in cytoskeleton arrangement and cell cycle, oxidative stress, apoptosis, metabolism/detoxification and stress. The presence of mucus layer had an impact on modulating the induced toxicity of NPs. NP-specific effects were

  14. Acid phosphatase and lipid peroxidation in human cataractous lens epithelium

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    Vasavada Abhay

    1993-01-01

    Full Text Available The anterior lens epithelial cells undergo a variety of degenerative and proliferative changes during cataract formation. Acid phosphatase is primarily responsible for tissue regeneration and tissue repair. The lipid hydroperoxides that are obtained by lipid peroxidation of polysaturated or unsaturated fatty acids bring about deterioration of biological membranes at cellular and tissue levels. Acid phosphatase and lipid peroxidation activities were studied on the lens epithelial cells of nuclear cataract, posterior subcapsular cataract, mature cataract, and mixed cataract. Of these, mature cataractous lens epithelium showed maximum activity for acid phosphatase (516.83 moles of p-nitrophenol released/g lens epithelium and maximum levels of lipid peroxidation (86.29 O.D./min/g lens epithelium. In contrast, mixed cataractous lens epithelium showed minimum activity of acid phosphatase (222.61 moles of p-nitrophenol released/g lens epithelium and minimum levels of lipid peroxidation (54.23 O.D./min/g lens epithelium. From our study, we correlated the maximum activity of acid phosphatase in mature cataractous lens epithelium with the increased areas of superimposed cells associated with the formation of mature cataract. Likewise, the maximum levels of lipid peroxidation in mature cataractous lens epithelium was correlated with increased permeability of the plasma membrane. Conversely, the minimum levels of lipid peroxidation in mixed cataractous lens epithelium makes us presume that factors other than lipid peroxidation may also account for the formation of mixed type of cataract.

  15. Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa

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    Mäki Markku

    2008-04-01

    Full Text Available Abstract Background Human gastrointestinal mucosa regenerates vigorously throughout life, but the factors controlling cell fate in mature mucosa are poorly understood. GATA transcription factors direct cell proliferation and differentiation in many organs, and are implicated in tumorigenesis. GATA-4 and GATA-6 are considered crucial for the formation of murine gastrointestinal mucosa, but their role in human gastrointestinal tract remains unexplored. We studied in detail the expression patterns of these two GATA factors and a GATA-6 down-stream target, Indian hedgehog (Ihh, in normal human gastrointestinal mucosa. Since these factors are considered important for proliferation and differentiation, we also explored the possible alterations in their expression in gastrointestinal neoplasias. The expression of the carcinogenesis-related protein Indian hedgehog was also investigated in comparison to GATA factors. Methods Samples of normal and neoplastic gastrointestinal tract from children and adults were subjected to RNA in situ hybridization with 33P labelled probes and immunohistochemistry, using an avidin-biotin immunoperoxidase system. The pathological tissues examined included samples of chronic and atrophic gastritis as well as adenomas and adenocarcinomas of the colon and rectum. Results GATA-4 was abundant in the differentiated epithelial cells of the proximal parts of the gastrointestinal tract but was absent from the distal parts. In contrast, GATA-6 was expressed throughout the gastrointestinal epithelium, and in the distal gut its expression was most intense at the bottom of the crypts, i.e. cells with proliferative capacity. Both factors were also present in Barrett's esophagus and metaplasia of the stomach. GATA-6 expression was reduced in colon carcinoma. Ihh expression overlapped with that of GATA-6 especially in benign gastrointestinal neoplasias. Conclusion The results suggest differential but overlapping functions for GATA-4 and

  16. Functional annotation of the human retinal pigment epithelium transcriptome

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    Gorgels Theo GMF

    2009-04-01

    Full Text Available Abstract Background To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE, the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy human donor eyes (aged 63–78 years were laser dissected and used for 22k microarray studies (Agilent technologies. Data were analyzed with Rosetta Resolver, the web tool DAVID and Ingenuity software. Results In total, we identified 19,746 array entries with significant expression in the RPE. Gene expression was analyzed according to expression levels, interindividual variability and functionality. A group of highly (n = 2,194 expressed RPE genes showed an overrepresentation of genes of the oxidative phosphorylation, ATP synthesis and ribosome pathways. In the group of moderately expressed genes (n = 8,776 genes of the phosphatidylinositol signaling system and aminosugars metabolism were overrepresented. As expected, the top 10 percent (n = 2,194 of genes with the highest interindividual differences in expression showed functional overrepresentation of the complement cascade, essential in inflammation in age-related macular degeneration, and other signaling pathways. Surprisingly, this same category also includes the genes involved in Bruch's membrane (BM composition. Among the top 10 percent of genes with low interindividual differences, there was an overrepresentation of genes involved in local glycosaminoglycan turnover. Conclusion Our study expands current knowledge of the RPE transcriptome by assigning new genes, and adding data about expression level and interindividual variation. Functional annotation suggests that the RPE has high levels of protein synthesis, strong energy demands, and is exposed to high levels of oxidative stress and a variable degree of inflammation. Our data sheds new light on the molecular composition of BM, adjacent to the

  17. Dopamine receptors in human gastrointestinal mucosa

    International Nuclear Information System (INIS)

    Hernandez, D.E.; Mason, G.A.; Walker, C.H.; Valenzuela, J.E.

    1987-01-01

    Dopamine is a putative enteric neurotransmitter that has been implicated in exocrine secretory and motility functions of the gastrointestinal tract of several mammalian species including man. This study was designed to determine the presence of dopamine binding sites in human gastric and duodenal mucosa and to describe certain biochemical characteristics of these enteric receptor sites. The binding assay was performed in triplicate with tissue homogenates obtained from healthy volunteers of both sexes using 3 H-dopamine as a ligand. The extent of nonspecific binding was determined in the presence of a 100-fold excess of unlabeled dopamine. Scatchard analysis performed with increasing concentrations of 3 H-dopamine (20-500 nM) revealed a single class of saturable dopamine binding sites in gastric and duodenal mucosa. The results of this report demonstrate the presence of specific dopamine receptors in human gastric and duodenal mucosa. These biochemical data suggest that molecular abnormalities of these receptor sites may be operative in the pathogenesis of important gastrointestinal disorders. 33 references, 2 figures

  18. Patient-specific three-dimensional explant spheroids derived from human nasal airway epithelium

    DEFF Research Database (Denmark)

    Marthin, June Kehlet; Stevens, Elizabeth Munkebjerg; Larsen, Lars Allan

    2017-01-01

    BACKGROUND: Three-dimensional explant spheroid formation is an ex vivo technique previously used in studies of airway epithelial ion and water transport. Explanted cells and sheets of nasal epithelium form fully differentiated spheroids enclosing a partly fluid-filled lumen with the ciliated apical...... surface facing the outside and accessible for analysis of ciliary function. METHODS: We performed a two-group comparison study of ciliary beat pattern and ciliary beat frequency in spheroids derived from nasal airway epithelium in patients with primary ciliary dyskinesia (PCD) and in healthy controls...... in the investigation of pathophysiological aspects and drug effects in human nasal airway epithelium....

  19. Regional variations of cell surface carbohydrates in human oral stratified epithelium

    DEFF Research Database (Denmark)

    Vedtofte, P; Dabelsteen, Erik; Hakomori, S

    1984-01-01

    The distribution of blood group carbohydrate chains with antigen A, B, H type 2 chain (A and B precursor), and N-acetyllactosamine (H type 2 precursor) specificity was studied in human oral epithelium from different anatomical regions. These represented various epithelial differentiation patterns...... epithelium from nine blood group A, two blood group B, and nine blood group O individuals. The blood group carbohydrate chains were examined in tissue sections by immunofluorescence microscopy. The A and B blood group antigens were detected by human blood group sera, and antigen H type 2 chains and N...... antigen H type 2 chains in metaplastically keratinized buccal epithelium was found to differ significantly from that seen in normal non-keratinized buccal epithelium. The regional variations demonstrated in cell surface carbohydrates are suggested to reflect differences in tissue differentiation....

  20. The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplay

    OpenAIRE

    Yilmaz, Özlem

    2008-01-01

    The microbiota of the human oral mucosa consists of a myriad of bacterial species that normally exist in commensal harmony with the host. Porphyromonas gingivalis, an aetiological agent in severe forms of periodontitis (a chronic inflammatory disease), is a prominent component of the oral microbiome and a successful colonizer of the oral epithelium. This Gram-negative anaerobe can also exist within the host epithelium without the existence of overt disease. Gingival epithelial cells, the oute...

  1. Intestinal subepithelial myofibroblasts support in vitro and in vivo growth of human small intestinal epithelium.

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    Nicholas Lahar

    Full Text Available The intestinal crypt-niche interaction is thought to be essential to the function, maintenance, and proliferation of progenitor stem cells found at the bases of intestinal crypts. These stem cells are constantly renewing the intestinal epithelium by sending differentiated cells from the base of the crypts of Lieberkühn to the villus tips where they slough off into the intestinal lumen. The intestinal niche consists of various cell types, extracellular matrix, and growth factors and surrounds the intestinal progenitor cells. There have recently been advances in the understanding of the interactions that regulate the behavior of the intestinal epithelium and there is great interest in methods for isolating and expanding viable intestinal epithelium. However, there is no method to maintain primary human small intestinal epithelium in culture over a prolonged period of time. Similarly no method has been published that describes isolation and support of human intestinal epithelium in an in vivo model. We describe a technique to isolate and maintain human small intestinal epithelium in vitro from surgical specimens. We also describe a novel method to maintain human intestinal epithelium subcutaneously in a mouse model for a prolonged period of time. Our methods require various growth factors and the intimate interaction between intestinal sub-epithelial myofibroblasts (ISEMFs and the intestinal epithelial cells to support the epithelial in vitro and in vivo growth. Absence of these myofibroblasts precluded successful maintenance of epithelial cell formation and proliferation beyond just a few days, even in the presence of supportive growth factors. We believe that the methods described here can be used to explore the molecular basis of human intestinal stem cell support, maintenance, and growth.

  2. TR146 cells grown on filters as a model of human buccal epithelium

    DEFF Research Database (Denmark)

    Nielsen, H M; Rassing, M R; Nielsen, Hanne Mørck

    2000-01-01

    The objective of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium. For this purpose, the permeability of water, mannitol and testosterone across the TR146 cell culture model was compared to the permeability across human, monkey...

  3. TR146 cells grown on filters as a model of human buccal epithelium

    DEFF Research Database (Denmark)

    Mørck Nielsen, H; Rømer Rassing, M; Nielsen, Hanne Mørck

    2000-01-01

    cell culture model, and human and porcine buccal epithelium were compared. The esterase activity in the intact cell culture model and in the porcine buccal mucosa was compared. Further, the TR146 cell culture model was used to study the permeability rate and metabolism of leu-enkephalin. The activity...... of the three enzymes in the TR146 homogenate supernatants was in the same range as the activity in homogenate supernatants of human buccal epithelium. In the TR146 cell culture model, the activity of aminopeptidase (13.70+/-2.10 nmol/min per mg protein) was approx. four times the activity of carboxypeptidase...

  4. TR146 cells grown on filters as a model of human buccal epithelium

    DEFF Research Database (Denmark)

    Nielsen, Hanne Mørck; Verhoef, J C; Ponec, M

    1999-01-01

    The aim of the present study was to characterize the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability of test substances with different molecular weights (M(w)). For this purpose, the apparent permeability (P(app)) values for mannitol...... and for fluorescein isothiocyanate (FITC)-labelled dextrans (FD) with various M(w) (4000-40000) were compared to the P(app) values obtained using porcine buccal mucosa as an in vitro model of the human buccal epithelium. The effect of 10 mM sodium glycocholate (GC) on the P(app) values was examined. To identify...

  5. Muscarinic cholinergic and alpha 2-adrenergic receptors in the epithelium and muscularis of the human ileum

    International Nuclear Information System (INIS)

    Lepor, H.; Rigaud, G.; Shapiro, E.; Baumann, M.; Kodner, I.J.; Fleshman, J.W.

    1990-01-01

    The aim of this study was to characterize the binding and functional properties of muscarinic cholinergic (MCh) and alpha 2-adrenergic receptors in the human ileum to provide insight into pharmacologic strategies for managing urinary and fecal incontinence after bladder and rectal replacement with intestinal segments. MCh and alpha 2-adrenergic binding sites were characterized in the epithelium and muscularis of eight human ileal segments with 3H-N-methylscopolamine and 3H-rauwolscine, respectively. The dissociation constant for 3H-N-methylscopolamine in the epithelium and muscularis was 0.32 +/- 0.07 nmol/L and 0.45 +/- 0.10 nmol/L, respectively (p = 0.32). The MCh receptor content was approximately eightfold greater in the muscularis compared with the epithelium (p = 0.008). The dissociation constant for 3H-rauwolscine in the muscularis and epithelium was 2.55 +/- 0.42 nmol/L and 2.03 +/- 0.19 nmol/L, respectively (p = 0.29). The alpha 2-adrenoceptor density was twofold greater in the epithelium compared with the muscularis (p = 0.05). Noncumulative concentration-response experiments were performed with carbachol, an MCh agonist, and UK-14304, a selective alpha 2-adrenergic agonist. The epithelium did not contract in the presence of high concentrations of carbachol and UK-14304. The muscularis preparations were responsive only to carbachol. The muscularis contains primarily MCh receptors mediating smooth muscle contraction. The alpha 2-adrenoceptors are localized primarily to the epithelium and may regulate water secretion in the intestine. The distribution and functional properties of ileal MCh and alpha 2-adrenergic receptors provide a theoretic basis for the treatment of incontinence after bladder and rectal replacement with intestinal segments

  6. Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways

    OpenAIRE

    Scull, Margaret A.; Gillim-Ross, Laura; Santos, Celia; Roberts, Kim L.; Bordonali, Elena; Subbarao, Kanta; Barclay, Wendy S.; Pickles, Raymond J.

    2009-01-01

    Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37 degrees C), avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human p...

  7. Expression of insulin signalling components in the sensory epithelium of the human saccule

    DEFF Research Database (Denmark)

    Degerman, Eva; Rauch, Uwe; Lindberg, Sven

    2013-01-01

    signalling components in the inner ear is sparce. Our immunohistochemistry approach has shown that the insulin receptor, insulin receptor substrate 1 (IRS1), protein kinase B (PKB) and insulin-sensitive glucose transporter (GLUT4) are expressed in the sensory epithelium of the human saccule, which also...

  8. Sodium transport and intracellular sodium activity in cultured human nasal epithelium

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Boucher, Richard C.

    1991-01-01

     human nasal epithelium (HNE). Under control conditions, intracellular Na+ activity (acNa) was 23 +/- 1 mM (n = 44 preparations, 393 impalements).Amiloride (10(-4) M) hyperpolarized the apical membrane and increased the fractional apical membrane resistance but did not affect acNa. Exposure to...

  9. TR146 cells grown on filters as a model of human buccal epithelium

    DEFF Research Database (Denmark)

    Nielsen, Hanne Mørck; Rassing, M R

    1999-01-01

    The aim of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability enhancement by different pH values, different osmolality values or bile salts. For this purpose, the increase in the apparent permeability (P...

  10. Gastrointestinal-active oligosaccharides from human milk and functional foods

    NARCIS (Netherlands)

    Albrecht, S.A.

    2011-01-01

    Keywords: human milk oligosaccharides (HMOs), galacto-oligosaccharides (GOS), konjac glucomannan (KGM), breast milk, baby feces, gastrointestinal metabolization, blood-group specific conjugates, CE-LIF-MSn

    Oligosaccharides, as present in human milk or supplemented to food, are

  11. Interstitial cells of Cajal in human gut and gastrointestinal disease

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J

    1999-01-01

    This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastrointestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective of their fun......This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastrointestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective...

  12. Neural influences on human intestinal epithelium in vitro.

    Science.gov (United States)

    Krueger, Dagmar; Michel, Klaus; Zeller, Florian; Demir, Ihsan E; Ceyhan, Güralp O; Slotta-Huspenina, Julia; Schemann, Michael

    2016-01-15

    We present the first systematic and, up to now, most comprehensive evaluation of the basic features of epithelial functions, such as basal and nerve-evoked secretion, as well as tissue resistance, in over 2200 surgical specimens of human small and large intestine. We found no evidence for impaired nerve-evoked epithelial secretion or tissue resistance with age or disease pathologies (stomach, pancreas or colon cancer, polyps, diverticulitis, stoma reversal). This indicates the validity of future studies on epithelial secretion or resistance that are based on data from a variety of surgical specimens. ACh mainly mediated nerve-evoked and basal secretion in the small intestine, whereas vasoactive intestinal peptide and nitric oxide were the primary pro-secretory transmitters in the large intestine. The results of the present study revealed novel insights into regional differences in nerve-mediated secretion in the human intestine and comprise the basis by which to more specifically target impaired epithelial functions in the diseased gut. Knowledge on basic features of epithelial functions in the human intestine is scarce. We used Ussing chamber techniques to record basal tissue resistance (R-basal) and short circuit currents (ISC; secretion) under basal conditions (ISC-basal) and after electrical field stimulation (ISC-EFS) of nerves in 2221 resectates from 435 patients. ISC-EFS was TTX-sensitive and of comparable magnitude in the small and large intestine. ISC-EFS or R-basal were not influenced by the patients' age, sex or disease pathologies (cancer, polyps, diverticulitis). Ion substitution, bumetanide or adenylate cyclase inhibition studies suggested that ISC-EFS depended on epithelial cAMP-driven chloride and bicarbonate secretion but not on amiloride-sensitive sodium absorption. Although atropine-sensitive cholinergic components prevailed for ISC-EFS of the duodenum, jejunum and ileum, PG97-269-sensitive [vasoactive intestinal peptide (VIP) receptor 1

  13. Distributions of elements in the human retinal pigment epithelium

    International Nuclear Information System (INIS)

    Ulshafer, R.J.; Allen, C.B.; Rubin, M.L.

    1990-01-01

    Distributions of elements above the atomic number of sodium were mapped in the retinal pigment epithelia of eight human eyes. X-ray energy spectra and maps were collected from cryofixed, freeze-dried, and epoxy-embedded tissues using energy-dispersive x-ray microanalysis. All eyes had high concentrations of phosphorus in the nuclei of retinal pigment epithelial cells. Melanosomes were rich in sulfur, zinc, calcium, and iron. Lipofuscin and cytoplasm contained only phosphorus and sulfur in detectable amounts. Drusen, when present, contained phosphorus and calcium. Six eyes had a prominent aluminum peak recorded from melanosomes, nuclei, and Bruch's membrane. In one pair of 90-year-old eyes, small, electron-dense deposits surrounded many melanosomes and contained mercury and selenium. Retinal pigment epithelial melanosomes may bind and accumulate metals and other potentially toxic ions over time, preventing them from reaching the neural retina

  14. Different alpha crystallin expression in human age-related and congenital cataract lens epithelium.

    Science.gov (United States)

    Yang, Jing; Zhou, Sheng; Guo, Minfei; Li, Yuting; Gu, Jianjun

    2016-05-28

    The purpose of this study was to investigate the different expressions of αA-crystallin and αB-crystallin in human lens epithelium of age-related and congenital cataracts. The central part of the human anterior lens capsule approximately 5 mm in diameter together with the adhering epithelial cells, were harvested and processed within 6 hours after cataract surgery from age-related and congenital cataract patients or from normal eyes of fresh cadavers. The mRNA and soluble protein levels of αA-crystallin and αB-crystallin in the human lens epithelium were detected by real-time PCR and western blots, respectively. The mRNA and soluble protein expressions of αA-crystallin and αB-crystallin in the lens epithelium were both reduced in age-related and congenital cataract groups when compared with the normal control group. However, the degree of α-crystallin loss in the lens epithelium was highly correlated with different cataract types. The α-crystallin expression of the lens epithelium was greatly reduced in the congenital cataract group but only moderately decreased in the age-related cataract group. The reduction of αA-crystallin soluble protein levels in the congenital cataract group was approximately 2.4 fold decrease compared with that of the age-related cataract group, while an mRNA fold change of 1.67 decrease was observed for the age-related cataract group. Similarly, the reduction of soluble protein levels of αB-crystallin in the congenital cataract group was approximately a 1.57 fold change compared with that of the age-related cataract group. A 1.75 fold change for mRNA levels compared with that of the age-related cataract group was observed. The results suggest that the differential loss of α-crystallin in the human lens epithelium could be associated with the different mechanisms of cataractogenesis in age-related versus congenital cataracts, subsequently resulting in different clinical presentations.

  15. Ion Transport in Human Pancreatic Duct Epithelium, Capan-1 Cells, Is Regulated by Secretin, VIP, Acetylcholine, and Purinergic Receptors

    DEFF Research Database (Denmark)

    Wang, Jing; Novak, Ivana

    2013-01-01

    OBJECTIVES: The objective of the study was to establish a solid model of polarized epithelium for human pancreatic ducts, where electrical parameters could be measured as indicators of ion transport. Further, we aimed to determine functional expression of several receptors, in particular, puriner...... transport in human pancreatic duct epithelium, Capan-1 cells, is regulated by secretin, VIP, acetylcholine, adenosine, and purinergic P2 receptors; and this human model has a good potential for studies of physiology and pathophysiology of pancreatic duct ion transport....

  16. Human gastrointestinal tolerance to D-tagatose.

    Science.gov (United States)

    Buemann, B; Toubro, S; Astrup, A

    1999-04-01

    D-Tagatose is a stereoisomer of D-fructose which is poorly absorbed in the small intestine and may, therefore, have potential as a reduced calorie bulk sweetener. However, one of the major limitations is the use of malabsorbed sugars is that their consumption may be associated with gastric discomfort. This is due to the osmotic impact of the sugar molecules remaining in the gut lumen for a prolonged period. We have performed a series of studies in which gastrointestinal symptoms have been recorded after the consumption of 29 or 30 g of D-tagatose. Nausea and diarrhea were reported with an incidence of 15.1 and 31.5%, respectively, in 73 healthy young male subjects in a screening study. Increased flatulence after D-tagatose was frequently reported in all the studies and the flatulence did not decline during a 15-day period with intake of 30 g in one dose daily. In most cases, symptoms were reported as light or moderate. However, the results suggest that 30 g taken at one time may be above the dose which should be recommended for ordinary use. Copyright 1999 Academic Press.

  17. Diversity of the human gastrointestinal tract microbiota revisited

    NARCIS (Netherlands)

    Rajilic-Stojanovic, M.; Smidt, H.; Vos, de W.M.

    2007-01-01

    Since the early days of microbiology, more than a century ago, representatives of over 400 different microbial species have been isolated and fully characterized from human gastrointestinal samples. However, during the past decade molecular ecological studies based on ribosomal RNA (rRNA) sequences

  18. Functional Development of the Human Gastrointestinal Tract: Hormone- and Growth Factor-Mediated Regulatory Mechanisms

    Directory of Open Access Journals (Sweden)

    Daniel Ménard

    2004-01-01

    Full Text Available The present review focuses on the control of gastrointestinal (GI tract development. The first section addresses the differences in general mechanisms of GI development in humans versus rodents, highlighting that morphogenesis of specific digestive organs and the differentiation of digestive epithelia occur not only at different stages of ontogeny but also at different rates. The second section provides an overview of studies from the author's laboratory at the Université de Sherbrooke pertaining to the development of the human fetal small intestine and colon. While both segments share similar morphological and functional characteristics, they are nevertheless modulated by distinct regulatory mechanisms. Using the organ culture approach, the author and colleagues were able to establish that hormones and growth factors, such as glucocorticoids, epidermal growth factor, insulin and keratinocyte growth factor, not only exert differential effects within these two segments, they can also trigger opposite responses in comparison with animal models. In the third section, emphasis is placed on the functional development of human fetal stomach and its various epithelial cell types; in particular, the glandular chief cells responsible for the synthesis and secretion of gastric enzymes such as pepsinogen-5 and gastric lipase. Bearing in mind that limitations of available cell models have, until now, greatly impeded the comprehension of molecular mechanisms regulating human gastric epithelial cell functions, the last section focuses on new human gastric epithelial cell models recently developed in the author's laboratory. These models comprise a novel primary culture system of human fetal gastric epithelium including, for the first time, functional chief cells, and human gastric epithelium cell lines cloned from the parental NCI-N87 strain. These new cells lines could serve important applications in the study of pathogenic action and epithelial

  19. Spontaneous and cytokine induced expression and activity of matrix metalloproteinases in human colonic epithelium

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Kirkegaard, T

    2009-01-01

    levels in cells from inflamed IBD mucosa. MMP-2 and -8 mRNA were expressed inconsistently and MMP-11, -13 and -14 mRNA undetectable. Proteolytic MMP activity was detected in CEC supernatants and the level was increased significantly in inflamed IBD epithelium. The enzyme activity was inhibited strongly......Matrix metalloproteinases (MMPs) have been implicated in tissue damage associated with inflammatory bowel disease (IBD).As the role of the intestinal epithelium in this process is unknown, we determined MMP expression and enzyme activity in human colonic epithelial cells (CEC). MMP mRNA expression...... was assessed by reverse transcription-polymerase chain reaction in HT-29 and DLD-1 cells and in CEC isolated from biopsies from IBD and control patients. Total MMP activity in the cells was measured by a functional assay, based on degradation of a fluorescent synthetic peptide containing the specific bond...

  20. Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.

    Science.gov (United States)

    Hartman, Kira G; Bortner, James D; Falk, Gary W; Ginsberg, Gregory G; Jhala, Nirag; Yu, Jian; Martín, Martín G; Rustgi, Anil K; Lynch, John P

    2014-09-01

    Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. © 2014 by the Society for Experimental Biology and Medicine.

  1. Surface to nuclear distances in human bronchial epithelium: Relationships to penetration by Rn daughters

    International Nuclear Information System (INIS)

    Baldwin, F.; Hovey, A.; McEwen, T.; O'Connor, R.; Unruh, H.; Bowden, D.H.

    1991-01-01

    Lung cancer in U miners is thought to be related to the inhalation of particulate Rn daughters. Since the depth of penetration by alpha particles is short, the thickness of the epithelium lining the bronchial tree may be a critical factor in the development of cancers at specific sites in the lung. The objectives of the study were to measure the thickness of the epithelium at all levels of the human bronchial tree, to determine the distances of epithelial nuclei from the mucociliary surface, and to compare these parameters in smokers and nonsmokers. Twenty-nine surgically removed specimens were examined; 26 were from smokers. No significant differences were found between smokers and nonsmokers, allowing us to treat the 29 cases as a homogeneous group. With progressive divisions of the bronchi, the epithelium decreases in thickness, and distances of nuclei from the surface are also less in the peripheral bronchi. Allowing for artefacts of tissue preparation, the mean distance from the mucociliary surface to the underlying nuclei varies between 17 and 38 microns

  2. Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium.

    Science.gov (United States)

    Amitani, R; Taylor, G; Elezis, E N; Llewellyn-Jones, C; Mitchell, J; Kuze, F; Cole, P J; Wilson, R

    1995-09-01

    The mechanisms by which Aspergillus fumigatus colonizes the respiratory mucosa are unknown. Culture filtrates of eight of nine clinical isolates of A. fumigatus slowed ciliary beat frequency and damaged human respiratory epithelium in vitro. These changes appeared to occur concurrently. Culture filtrates of two clinical isolates of Candida albicans had no effect on ciliated epithelium. We have purified and characterized cilioinhibitory factors of a clinical isolate of A. fumigatus. The cilioinhibitory activity was heat labile, reduced by dialysis, and partially extractable into chloroform. The activity was associated with both high- and low-molecular-weight factors, as determined by gel filtration on Sephadex G-50. A low-molecular-weight cilioinhibitory factor was further purified by reverse-phase high-performance liquid chromatography and shown by mass spectrometry to be gliotoxin, a known metabolite of A. fumigatus. Gliotoxin significantly slowed ciliary beat frequency in association with epithelial damage at concentrations above 0.2 microgram/ml; other Aspergillus toxins, i.e., fumagillin and helvolic acid, were also cilioinhibitory but at much higher concentrations. High-molecular-weight (> or = 35,000 and 25,000) cilioinhibitory materials had neither elastolytic nor proteolytic activity and remain to be identified. Thus, A. fumigatus produces a number of biologically active substances which slow ciliary beating and damage epithelium and which may influence colonization of the airways.

  3. Radiation-induced functional damages in the regeneration system for the gastrointestinal epithelium cell and analysis of its nutritional modification

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Kazuhiko; Narita, Mayumi; Ogawa, Yuko; Shinohara, Kiyoko; Nakazawa, Yukiko; Yamada, Keiko [National Inst. of Health and Nutrition, Tokyo (Japan)

    2000-02-01

    It has been known that the stem cells of villus-crypt zone are highly sensitive to radiation exposure. In this study, radiation-induced damages in gastrointestinal cell regeneration system were investigated from an aspect of nutritional factors to clarify the damages in digestive functions caused by X-ray exposure and recovery from them. The activities of digestive enzymes in the small intestine after in vivo X-ray exposure at 100 Gy were determined. The sucrose activity in the upper intestine was gradually reduced to about a half 3 days after the exposure. This change pattern of activity was also observed in other regions in the intestine. This tendency was similar to that of trehalase activity, but the changes in alkaline phosphatase and leucine amino-peptidase activities were less than the above two enzymes. Therefore, time course changes of sucrose and trehalase pattern in the villus-crypt zone were monitored after radiation exposure. Either of the two enzyme activities was low in the crypt and gradually increased from the basement of villus to its top. These activities were dose-dependently reduced by X-ray exposure. Especially it was marked for trehalose activity. Moreover, the amounts of short-chain fatty acids such as acetic acid, propionic acid, butylic acid in the cecum were determined. Significant increases in acetic acid and propionic acid contents were fount at 1 or 2 days after the X-ray exposure. These increases in fatty acids contents were more distinctive in the animals that received forced and free administration of food than those that received free administration alone. The presence of food components in the intestine might be effective for protecting the mucous membrane regeneration from radiation exposure. (M.N.)

  4. Myiasis gastrointestinal humana por Eristalis tenax Gastrointestinal human myiasis for Eristalis tenax

    Directory of Open Access Journals (Sweden)

    Marcelo Kun

    1998-08-01

    Full Text Available Son caracterizadas las myiasis registradas en Bariloche y establecidas las condiciones probables bajo las cuales se produjeron las infestaciones. Las larvas obtenidas a partir de heces de 2 pacientes fueron identificadas como Eristalis tenax (Diptera: Syrphidae de acuerdo a las claves de Hartley (1961 y Organización Panamericana de la Salud (1962. Estos 2 casos de myiasis gastrointestinal humana constituyen los primeros registrados en Bariloche (Patagonia, Argentina y sus características responden a las registradas para esta especie de Díptera en otras partes del mundo. La falta de control específico en el sistema domiciliario de suministro de agua ha sido la causa más probable de la infestación. Este registro extiende la distribución de E. tenax y de las myiasis gastrointestinales humanas en América del Sur hasta los 41º 03' S.Foram caracterizadas as miasis registradas em Bariloche (Patagonia, Argentina e estabelecidas as prováveis condições sob as quais são produzidas as infestações. As larvas obtidas a partir das fezes de dois pacientes foram identificadas como Eristalis tenax (Diptera: Syrphdae. Esses dois casos de miasis gastrointestinal humana foram os primeiros registrados em Bariloche, Argentina, e suas características respondem às registradas para esta espécie de Diptera em outras partes do mundo. A falta de controle específico no sistema domiciliário de abastecimento de água tem sido a causa mais provável de infestação. Este registro amplia a distribuição de E. tenax e das miasis gastrointestinais humanas em América do Sul até os 41º 03's.The myiasis observed in Bariloche are characterized and the probable conditions under which the infestations took place established. The larvae obtained from faeces of 2 patients were identified as Eristalis tenax (Diptera: Syrphidae according to Hartley (1961 and Organización Panamericana de la Salud keys (1962. These 2 cases of human gastrointestinal myiasis were the

  5. APR-246/PRIMA-1Met Inhibits and Reverses Squamous Metaplasia in Human Conjunctival Epithelium.

    Science.gov (United States)

    Li, Jing; Li, Cheng; Wang, Guoliang; Liu, Zhen; Chen, Pei; Yang, Qichen; Dong, Nuo; Wu, Huping; Liu, Zuguo; Li, Wei

    2016-02-01

    Squamous metaplasia is a common pathologic condition in ocular surface diseases for which there is no therapeutic medication in clinic. In this study, we investigated the effect of a small molecule, APR-246/PRIMA-1(Met), on squamous metaplasia in human conjunctival epithelium. Human conjunctival explants were cultured for up to 12 days under airlifting conditions. Epithelial cell differentiation and proliferation were assessed by Cytokeratin 10 (K10), K14, K19, Pax6, MUC5AC, and p63 immunostaining patterns. β-catenin and TCF-4 immunofluorescent staining and real-time PCR characterized Wnt signaling pathway involvement. Pterygium clinical samples were cultured under airlifting conditions with or without APR-246 for 4 days. p63, K10, β-catenin, and TCF-4 expression in pterygial epithelium was determined by immunofluorescent staining and real-time PCR. Airlift conjunctival explants resulted in increased stratification and intrastromal epithelial invagination. Such pathology was accompanied by increases in K10, K14, and p63 expression, whereas K19 and Pax6 levels declined when compared to those in freshly isolated tissue. On the other hand, APR-246 reversed all of these declines in K10, K14, and p63 expression. Furthermore, K19 and Pax6 increased along with rises in goblet cell density. These effects of APR-246 were accompanied by near restoration of normal conjunctival epithelial histology. APR-246 also reversed squamous metaplasia in pterygial epithelium that had developed after 4 days in ex vivo culture. Reductions in squamous metaplasia induced by APR-246 suggest it may provide a novel therapeutic approach in different squamous metaplasia-associated ocular surface diseases.

  6. Demonstration of carboxylesterase in cytology samples of human nasal respiratory epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Rodgers, D.A.; Nikula, K.J.; Avila, K. [and others

    1995-12-01

    The epithelial lining of the nasal airways is a target for responses induced by a variety of toxicant exposures. The high metabolic capacity of this tissue has been suggested to play a role in both protection of the airways through detoxication of certain toxicants, as well as in activation of other compounds to more toxic metabolites. Specifically, nasal carboxylesterase (CE) has been shown to mediate the toxicity of inhaled esters and acrylates by converting them to more toxic acid and alcohol metabolites which can be cytotoxic and/or carcinogenic to the nasal mucosa. Due to difficulties in extrapolating rodent models to human, new paradigms using human cells and tissues are essential to understanding and evaluating the metabolic processes in human nasal epithelium.

  7. Frequency of human papillomavirus infection in patients with gastrointestinal cancer.

    Science.gov (United States)

    Roesch-Dietlen, F; Cano-Contreras, A D; Sánchez-Maza, Y J; Espinosa-González, J M; Vázquez-Prieto, M Á; Valdés-de la O, E J; Díaz-Roesch, F; Carrasco-Arroniz, M Á; Cruz-Palacios, A; Grube-Pagola, P; Sumoza-Toledo, A; Vivanco-Cid, H; Mellado-Sánchez, G; Meixueiro-Daza, A; Silva-Cañetas, C S; Carrillo-Toledo, M G; Lagunes-Torres, R; Amieva-Balmori, M; Gómez-Castaño, P C; Reyes-Huerta, J U; Remes-Troche, J M

    2018-02-15

    Cancer is the result of the interaction of genetic and environmental factors. It has recently been related to viral infections, one of which is human papillomavirus. The aim of the present study was to describe the frequency of human papillomavirus infection in patients with digestive system cancers. A prospective, multicenter, observational study was conducted on patients with gastrointestinal cancer at 2public healthcare institutes in Veracruz. Two tumor samples were taken, one for histologic study and the other for DNA determination of human papillomavirus and its genotypes. Anthropometric variables, risk factors, sexual habits, tumor location, and histologic type of the cancer were analyzed. Absolute and relative frequencies were determined using the SPSS version 24.0 program. Fifty-three patients were studied. They had gastrointestinal cancer located in: the colon (62.26%), stomach (18.87%), esophagus (7.55%), rectum (7.55%), and small bowel (3.77%). Human papillomavirus was identified in 11.32% of the patients, 66.7% of which corresponded to squamous cell carcinoma and 33.3% to adenocarcinoma. Only genotype 18 was identified. Mean patient age was 61.8±15.2 years, 56.60% of the patients were men, and 43.40% were women. A total of 15.8% of the patients had a family history of cancer and 31.6% had a personal history of the disease, 38.6% were tobacco smokers, and 61.4% consumed alcohol. Regarding sex, 5.3% of the patients said they were homosexual, 3.5% were bisexual, 29.8% engaged in oral sex, and 24.6% in anal sex. Our study showed that human papillomavirus infection was a risk factor for the development of gastrointestinal cancer, especially of squamous cell origin. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  8. The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplay.

    Science.gov (United States)

    Yilmaz, Ozlem

    2008-10-01

    The microbiota of the human oral mucosa consists of a myriad of bacterial species that normally exist in commensal harmony with the host. Porphyromonas gingivalis, an aetiological agent in severe forms of periodontitis (a chronic inflammatory disease), is a prominent component of the oral microbiome and a successful colonizer of the oral epithelium. This Gram-negative anaerobe can also exist within the host epithelium without the existence of overt disease. Gingival epithelial cells, the outer lining of the gingival mucosa, which function as an important part of the innate immune system, are among the first host cells colonized by P. gingivalis. This review describes recent studies implicating the co-existence and intracellular adaptation of the organism in these target host cells. Specifically, recent findings on the putative mechanisms of persistence, intercellular dissemination and opportunism are highlighted. These new findings may also represent an original and valuable model for mechanistic characterization of other successful host-adapted, self-limiting, persistent intracellular bacteria in human epithelial tissues.

  9. Multilayered epithelium in a rat model and human Barrett's esophagus: Similar expression patterns of transcription factors and differentiation markers

    Directory of Open Access Journals (Sweden)

    Yang Chung S

    2008-01-01

    Full Text Available Abstract Background In rats, esophagogastroduodenal anastomosis (EGDA without concomitant chemical carcinogen treatment leads to gastroesophageal reflux disease, multilayered epithelium (MLE, a presumed precursor in intestinal metaplasia, columnar-lined esophagus, dysplasia, and esophageal adenocarcinoma. Previously we have shown that columnar-lined esophagus in EGDA rats resembled human Barrett's esophagus (BE in its morphology, mucin features and expression of differentiation markers (Lab. Invest. 2004;84:753–765. The purpose of this study was to compare the phenotype of rat MLE with human MLE, in order to gain insight into the nature of MLE and its potential role in the development of BE. Methods Serial sectioning was performed on tissue samples from 32 EGDA rats and 13 patients with established BE. Tissue sections were immunohistochemically stained for a variety of transcription factors and differentiation markers of esophageal squamous epithelium and intestinal columnar epithelium. Results We detected MLE in 56.3% (18/32 of EGDA rats, and in all human samples. As expected, both rat and human squamous epithelium, but not intestinal metaplasia, expressed squamous transcription factors and differentiation markers (p63, Sox2, CK14 and CK4 in all cases. Both rat and human intestinal metaplasia, but not squamous epithelium, expressed intestinal transcription factors and differentiation markers (Cdx2, GATA4, HNF1α, villin and Muc2 in all cases. Rat MLE shared expression patterns of Sox2, CK4, Cdx2, GATA4, villin and Muc2 with human MLE. However, p63 and CK14 were expressed in a higher proportion of rat MLE compared to humans. Conclusion These data indicate that rat MLE shares similar properties to human MLE in its expression pattern of these markers, not withstanding small differences, and support the concept that MLE may be a transitional stage in the metaplastic conversion of squamous to columnar epithelium in BE.

  10. Impact of Oat-Based Products on Human Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Staka Aiga

    2015-09-01

    Full Text Available Oat is rich in valuable nutrients. In comparison to other cereals, oat contains more total proteins, carbohydrate, fat, non-starch fibre, as well as unique antioxidants (one of them - avenanthramides, vitamins, and minerals. One of the most often studied components of oats is β-glucan - a type of soluble dietary fibre located throughout the starch endosperm, but with highest concentration in the bran. Many studies have shown the beneficial health effects of oat β-glucan as a soluble dietary fibre. Until now, most of the studies on this nutrient have been conducted in the cardiovascular and diabetology field. This article aimed to review the literature on studies that investigated the effects of oat-based products on human gastrointestinal tract - gastrointestinal microflora, irritable bowel syndrome, inflammatory bowel disease as well as prevention/treatment of colorectal cancer. A literature search was conducted using PubMed database. More than 80 potential articles were identified, which were selected afterwards according to aims of our study. Studies done on human were preferred. A long-term dietary intake of oat-based products improves human intestinal microflora, could have benefits in irritable bowel syndrome, and probable effects were seen in patients with ulcerative colitis, but this remains to be proven. There are few studies regarding prevention/treatment of colorectal cancer and they do not show clear benefit nor provide recommendations.

  11. Gene expression and functional annotation of the human and mouse choroid plexus epithelium.

    Directory of Open Access Journals (Sweden)

    Sarah F Janssen

    Full Text Available BACKGROUND: The choroid plexus epithelium (CPE is a lobed neuro-epithelial structure that forms the outer blood-brain barrier. The CPE protrudes into the brain ventricles and produces the cerebrospinal fluid (CSF, which is crucial for brain homeostasis. Malfunction of the CPE is possibly implicated in disorders like Alzheimer disease, hydrocephalus or glaucoma. To study human genetic diseases and potential new therapies, mouse models are widely used. This requires a detailed knowledge of similarities and differences in gene expression and functional annotation between the species. The aim of this study is to analyze and compare gene expression and functional annotation of healthy human and mouse CPE. METHODS: We performed 44k Agilent microarray hybridizations with RNA derived from laser dissected healthy human and mouse CPE cells. We functionally annotated and compared the gene expression data of human and mouse CPE using the knowledge database Ingenuity. We searched for common and species specific gene expression patterns and function between human and mouse CPE. We also made a comparison with previously published CPE human and mouse gene expression data. RESULTS: Overall, the human and mouse CPE transcriptomes are very similar. Their major functionalities included epithelial junctions, transport, energy production, neuro-endocrine signaling, as well as immunological, neurological and hematological functions and disorders. The mouse CPE presented two additional functions not found in the human CPE: carbohydrate metabolism and a more extensive list of (neural developmental functions. We found three genes specifically expressed in the mouse CPE compared to human CPE, being ACE, PON1 and TRIM3 and no human specifically expressed CPE genes compared to mouse CPE. CONCLUSION: Human and mouse CPE transcriptomes are very similar, and display many common functionalities. Nonetheless, we also identified a few genes and pathways which suggest that the CPE

  12. Effects of ionizing radiation on glycerolated amniotic membranes as a substract for cultured human epithelium

    International Nuclear Information System (INIS)

    Paggiaro, Andre Oliveira

    2011-01-01

    The amniotic membrane (AM) is a biomaterial with biological properties that are beneficial to tissue repair. It has been used as a temporary coverage to threat burns and chronic wounds. Recently, it has been served as a substrate for keratinocytes culture to construct a living skin equivalent. However, MA is a biological material, and its transplantation could cause infectious disease for receptors. So, it must be preserved and sterilized before clinical use. The aim of this study was to evaluate the radiation effects on glycerol-preserved MA, considering its compatibility to support human keratinocytes culture. Four MA were stored in high concentrations of glycerol (> 85%) and half of them were radio sterilized with a dose of 25 kGy. Then, we established two groups: nonirradiated MA (MA-ni) and irradiated MA (MA-i). Both groups was deepithelialized by a standardized protocol and was investigated morphologically, immunohistochemical and ultrastructural. Subsequently human keratinocytes were cultivated immersed and in air-liquid interface on denuded surface of MA-i and MA-ni. The results were compared at 14 and 21 days of culture by light and electron microscopy. After epithelial denudation, analyses demonstrated the continuity of the basement membrane in MA-ni group, whereas in the irradiated group, there was no indication of the basement membrane’s presence on the surface of MA. The cell cultures showed that in the non-irradiated group, there was growth of a multi-layered and differentiated epithelium, with a stratum corneum’s formation in air-liquid interface. In the irradiated group, the epithelium had only two or three layer, little cell differentiation, with the same results immersed or air-liquid interface system. Glycerol-preserved MA was biocompatible with the growth of a cultivated epithelium, showing its potential as a skin substitute. Irradiation at 25 kGy cause structural damage to the tissue, making changes in basement membrane, that facilitates

  13. Human forniceal region is the stem cell-rich zone of the conjunctival epithelium.

    Science.gov (United States)

    Harun, Mohd Hairul Nizam; Sepian, Siti Norzalehawati; Chua, Kien-Hui; Ropilah, Abd Rahman; Abd Ghafar, Norzana; Che-Hamzah, Jemaima; Bt Hj Idrus, Ruszymah; Annuar, Faridah Hanom

    2013-03-01

    The anterior surface of the eye is covered by several physically contiguous but histologically distinguishable epithelia overlying the cornea, limbus, bulbar conjunctiva, fornix conjunctiva, and palpebral conjunctiva. The self-renewing nature of the conjunctival epithelia makes their long-term survival ultimately dependent on small populations of stem cells. Hence, the objective of this study was to investigate the expression of the stem cell genes Sox2, OCT4, NANOG, Rex1, NES, and ABCG2 in cultured human conjunctival epithelium from different conjunctival zones, namely, the bulbar, palpebral and fornix zones. Three samples were taken from patients with primary pterygium and cataract (age range 56-66 years) who presented to our eye clinic at the UKM Medical Centre. The eye was examined with slit lamp to ensure there was no underlying ocular surface diseases and glaucoma. Conjunctival tissue was taken from patients who underwent a standard cataract or pterygium operation as a primary procedure. Tissues were digested, cultured, and propagated until an adequate number of cells was obtained. Total RNA was extracted and subjected to expression analysis of conjunctival epithelium genes (KRT4, KRT13, KRT19) and stem cell genes (Sox2, OCT4, NANOG, Rex1, NES, ABCG2) by reverse transcriptase-PCR and 2% agarose gel electrophoresis. The expression of Sox2, OCT4, and NANOG genes were detected in the fornical cells, while bulbar cells only expressed Sox2 and palpebral cells only expressed OCT4. Based on these results, the human forniceal region expresses a higher number of stem cell genes than the palpebral and bulbar conjunctiva.

  14. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, A.; Gorgels, T.G.M.F.; ten Brink, J.B.; van der Spek, P.J.; Bossers, K.; Heine, V.M.; Bergen, A.A.

    2015-01-01

    Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  15. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles : Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G M F; Ten Brink, Jacoline B; van der Spek, Peter J; Bossers, Koen; Heine, Vivi M; Bergen, Arthur A

    2015-01-01

    BACKGROUND: The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  16. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

    2015-01-01

    The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new

  17. Generation of Gastrointestinal Organoids from Human Pluripotent Stem Cells.

    Science.gov (United States)

    Múnera, Jorge O; Wells, James M

    2017-01-01

    Over the past several decades, developmental biologists have discovered fundamental mechanisms by which organs form in developing embryos. With this information it is now possible to generate human "organoids" by the stepwise differentiation of human pluripotent stem cells using a process that recapitulates organ development. For the gastrointestinal tract, one of the first key steps is the formation of definitive endoderm and mesoderm, a process that relies on the TGFb molecule Nodal. Endoderm is then patterned along the anterior-posterior axis, with anterior endoderm forming the foregut and posterior endoderm forming the mid and hindgut. A-P patterning of the endoderm is accomplished by the combined activities of Wnt, BMP, and FGF. High Wnt and BMP promote a posterior fate, whereas repressing these pathways promotes an anterior endoderm fate. The stomach derives from the posterior foregut and retinoic acid signaling is required for promoting a posterior foregut fate. The small and large intestine derive from the mid and hindgut, respectively.These stages of gastrointestinal development can be precisely manipulated through the temporal activation and repression of the pathways mentioned above. For example, stimulation of the Nodal pathway with the mimetic Activin A, another TGF-β superfamily member, can trigger the differentiation of pluripotent stem cells into definitive endoderm (D'Amour et al., Nat Biotechnol 23:1534-1541, 2005). Exposure of definitive endoderm to high levels of Wnt and FGF promotes the formation of posterior endoderm and mid/hindgut tissue that expresses CDX2. Mid-hindgut spheroids that are cultured in a three-dimensional matrix form human intestinal organoids (HIOs) that are small intestinal in nature Spence et al., Nature 2011. In contrast, activation of FGF and Wnt in the presence of the BMP inhibitor Noggin promotes the formation of anterior endoderm and foregut tissues that express SOX2. These SOX2-expressing foregut spheroids can be

  18. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium.

    Science.gov (United States)

    Sato, Toshiro; Stange, Daniel E; Ferrante, Marc; Vries, Robert G J; Van Es, Johan H; Van den Brink, Stieneke; Van Houdt, Winan J; Pronk, Apollo; Van Gorp, Joost; Siersema, Peter D; Clevers, Hans

    2011-11-01

    We previously established long-term culture conditions under which single crypts or stem cells derived from mouse small intestine expand over long periods. The expanding crypts undergo multiple crypt fission events, simultaneously generating villus-like epithelial domains that contain all differentiated types of cells. We have adapted the culture conditions to grow similar epithelial organoids from mouse colon and human small intestine and colon. Based on the mouse small intestinal culture system, we optimized the mouse and human colon culture systems. Addition of Wnt3A to the combination of growth factors applied to mouse colon crypts allowed them to expand indefinitely. Addition of nicotinamide, along with a small molecule inhibitor of Alk and an inhibitor of p38, were required for long-term culture of human small intestine and colon tissues. The culture system also allowed growth of mouse Apc-deficient adenomas, human colorectal cancer cells, and human metaplastic epithelia from regions of Barrett's esophagus. We developed a technology that can be used to study infected, inflammatory, or neoplastic tissues from the human gastrointestinal tract. These tools might have applications in regenerative biology through ex vivo expansion of the intestinal epithelia. Studies of these cultures indicate that there is no inherent restriction in the replicative potential of adult stem cells (or a Hayflick limit) ex vivo. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  19. Aspects of nitrogen dioxide toxicity in environmental urban concentrations in human nasal epithelium

    International Nuclear Information System (INIS)

    Koehler, C.; Ginzkey, C.; Friehs, G.; Hackenberg, S.; Froelich, K.; Scherzed, A.; Burghartz, M.; Kessler, M.; Kleinsasser, N.

    2010-01-01

    Cytotoxicity and genotoxicity of nitrogen dioxide (NO 2 ) as part of urban exhaust pollution are widely discussed as potential hazards to human health. This study focuses on toxic effects of NO 2 in realistic environmental concentrations with respect to the current limit values in a human target tissue of volatile xenobiotics, the epithelium of the upper aerodigestive tract. Nasal epithelial cells of 10 patients were cultured as an air-liquid interface and exposed to 0.01 ppm NO 2 , 0.1 ppm NO 2 , 1 ppm NO 2 , 10 ppm NO 2 and synthetic air for half an hour. After exposure, genotoxicity was evaluated by the alkaline single-cell microgel electophoresis (Comet) assay and by induction of micronuclei in the micronucleus test. Depression of proliferation and cytotoxic effects were determined using the micronucleus assay and trypan blue exclusion assay, respectively. The experiments revealed genotoxic effects by DNA fragmentation starting at 0.01 ppm NO 2 in the Comet assay, but no micronucleus inductions, no changes in proliferation, no signs of necrosis or apoptosis in the micronucleus assay, nor did the trypan blue exclusion assay show any changes in viability. The present data reveal a possible genotoxicity of NO 2 in urban concentrations in a screening test. However, permanent DNA damage as indicated by the induction of micronuclei was not observed. Further research should elucidate the effects of prolonged exposure.

  20. Vomeronasal versus olfactory epithelium: is there a cellular basis for human vomeronasal perception?

    Science.gov (United States)

    Witt, Martin; Hummel, Thomas

    2006-01-01

    The vomeronasal organ (VNO) constitutes an accessory olfactory organ that receives chemical stimuli, pheromones, which elicit behavioral, reproductive, or neuroendocrine responses among individuals of the same species. In many macrosmatic animals, the morphological substrate constitutes a separate organ system consisting of a vomeronasal duct (ductus vomeronasalis, VND), equipped with chemosensory cells, and a vomeronasal nerve (nervus vomeronasalis, VNN) conducting information into the accessory olfactory bulb (AOB) in the central nervous system (CNS). Recent data require that the long-accepted dual functionality of a main olfactory system and the VNO be reexamined, since all species without a VNO are nevertheless sexually active, and species possessing a VNO also can sense other than "vomeronasal" stimuli via the vomeronasal epithelium (VNE). The human case constitutes a borderline situation, as its embryonic VNO anlage exerts a developmental track common to most macrosmatics, but later typical structures such as the VNN, AOB, and probably most of the chemoreceptor cells within the still existent VND are lost. This review also presents recent information on the VND including immunohistochemical expression of neuronal markers, intermediate filaments, lectins, integrins, caveolin, CD44, and aquaporins. Further, we will address the issue of human pheromone candidates.

  1. Translational neuropharmacology: the use of human isolated gastrointestinal tissues.

    Science.gov (United States)

    Sanger, G J; Broad, J; Kung, V; Knowles, C H

    2013-01-01

    Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age, gender, genetic background and disease. Here, these are discussed with reference to neuromuscular and neurosecretory functions of the human gastrointestinal (GI) tract. Tissues are obtained after informed consent, in collaboration with surgeons (surgical techniques help minimize variables) and pathologists. Given the difficulties of directly recording from human myenteric neurones (embedded between muscle layers), enteric motor nerve functions are studied by measuring muscle contractions/relaxations evoked by electrical stimulation of intrinsic nerves; responses are regionally dependent, often involving cholinergic and nitrergic phenotypes. Enteric sensory functions can be studied by evoking the peristaltic reflex, involving enteric sensory and motor nerves, but this has rarely been achieved. As submucosal neurones are more accessible (after removing the mucosa), direct neuronal recordings are possible. Neurosecretory functions are studied by measuring changes in short-circuit current across the mucosa. For all experiments, basic questions must be addressed. Because tissues are from patients, what are the controls and the influence of disease? How long does it take before function fully recovers? What is the impact of age- and gender-related differences? What is the optimal sample size? Addressing these and other questions minimizes variability and raises the scientific credibility of human tissue research. Such studies also reduce animal use. Further, the many differences between animal and human GI functions also means that human tissue research must question the ethical validity of using strains of animals with unproved translational significance. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  2. Merkel-like cell distribution in the epithelium of the human vagina. An immunohistochemical and TEM study.

    Science.gov (United States)

    Polakovičová, Simona; Csöbönyeiová, Mária; Filova, Barbora; Borovský, Miroslav; Maršík, Ladislav; Kvasilová, Alena; Polák, Štefan

    2018-02-16

    Human Merkel cells (MCs) were first described by Friedrich S. Merkel in 1875 and named "Tastzellen" (touch cells). Merkel cells are primarily localized in the basal layer of the epidermis and concentrated in touch-sensitive areas. In our previous work, we reported on the distribution of MCs in the human esophagus, so therefore we chose other parts of the human body to study them. We selected the human vagina, because it has a similar epithelium as the esophagus and plays very important roles in reproduction and sexual pleasure. Due to the fact that there are very few research studies focusing on the innervation of this region, we decided to investigate the occurrence of MCs in the anterior wall of the vagina. The aim of our research was to identify MCs in the stratified squamous non-keratinized epithelium of the human vagina in 20 patients. For the identification of Merkel cells by light microscopy, we used antibodies against simple-epithelial cytokeratins (especially anti-cytokeratin 20). We also tried to identify them using transmission electron microscopy. Our investigation confirmed that 10 (50 %) of 20 patients had increased number of predominantly intraepithelial CK20 positive "Merkel-like" cells (MLCs) in the human vaginal epithelium. Subepithelial CK20 positive MLCs were observed in only one patient (5%). We tried to identify them also using transmission electron microscopy. Our investigation detected some unique cells that may be MCs. The purpose of vaginal innervation is still unclear. There are no data available concerning the distribution of MCs in the human vagina, so it would be interesting to study the role of MCs in the vaginal epithelium, in the context of innervation and epithelial biology.

  3. A Mouse Model of Hyperproliferative Human Epithelium Validated by Keratin Profiling Shows an Aberrant Cytoskeletal Response to Injury

    Directory of Open Access Journals (Sweden)

    Samal Zhussupbekova

    2016-07-01

    Full Text Available A validated animal model would assist with research on the immunological consequences of the chronic expression of stress keratins KRT6, KRT16, and KRT17, as observed in human pre-malignant hyperproliferative epithelium. Here we examine keratin gene expression profile in skin from mice expressing the E7 oncoprotein of HPV16 (K14E7 demonstrating persistently hyperproliferative epithelium, in nontransgenic mouse skin, and in hyperproliferative actinic keratosis lesions from human skin. We demonstrate that K14E7 mouse skin overexpresses stress keratins in a similar manner to human actinic keratoses, that overexpression is a consequence of epithelial hyperproliferation induced by E7, and that overexpression further increases in response to injury. As stress keratins modify local immunity and epithelial cell function and differentiation, the K14E7 mouse model should permit study of how continued overexpression of stress keratins impacts on epithelial tumor development and on local innate and adaptive immunity.

  4. SMAD4 regulates cell motility through transcription of N-cadherin in human pancreatic ductal epithelium.

    Directory of Open Access Journals (Sweden)

    Ya'an Kang

    Full Text Available Expression of the cellular adhesion protein N-cadherin is a critical event during epithelial-mesenchymal transition (EMT. The SMAD4 protein has been identified as a mediator of transforming growth factor-β (TGF-β superfamily signaling, which regulates EMT, but the mechanisms linking TGF-β signaling to N-cadherin expression remain unclear. When the TGF-β pathway is activated, SMAD proteins, including the common mediator SMAD4, are subsequently translocated into the nucleus, where they influence gene transcription via SMAD binding elements (SBEs. Here we describe a mechanism for control of CDH2, the gene encoding N-cadherin, through the canonical TGFβ-SMAD4 pathway. We first identified four previously undescribed SBEs within the CDH2 promoter. Using telomerase immortalized human pancreatic ductal epithelium, we found that TGF-β stimulation prompted specific SMAD4 binding to all four SBEs. Luciferase reporter and SMAD4-knockdown experiments demonstrated that specific SMAD4 binding to the SBE located at -3790 bp to -3795 bp within the promoter region of CDH2 was necessary for TGF-β-stimulated transcription. Expression of N-cadherin on the surface of epithelial cells facilitates motility and invasion, and we demonstrated that knockdown of SMAD4 causes decreased N-cadherin expression, which results in diminished migration and invasion of human pancreatic ductal epithelial cells. Similar reduction of cell motility was produced after CDH2 knockdown. Together, these findings suggest that SMAD4 is critical for the TGF-β-driven upregulation of N-cadherin and the resultant invasive phenotype of human pancreatic ductal epithelial cells during EMT.

  5. Cytotoxicity and genotoxicity of bacterial magnetosomes against human retinal pigment epithelium cells

    Science.gov (United States)

    Qi, Lei; Lv, Xiujuan; Zhang, Tongwei; Jia, Peina; Yan, Ruiying; Li, Shuli; Zou, Ruitao; Xue, Yuhua; Dai, Liming

    2016-06-01

    A variety of nanomaterials have been developed for ocular diseases. The ability of these nanomaterials to pass through the blood-ocular barrier and their biocompatibility are essential characteristics that must be considered. Bacterial magnetosomes (BMs) are a type of biogenic magnetic nanomaterials synthesized by magnetotactic bacteria. Due to their unique biomolecular membrane shell and narrow size distribution of approximately 30 nm, BMs can pass through the blood-brain barrier. The similarity of the blood-ocular barrier to the blood-brain barrier suggests that BMs have great potential as treatments for ocular diseases. In this work, BMs were isolated from magnetotactic bacteria and evaluated in various cytotoxicity and genotoxicity studies in human retinal pigment epithelium (ARPE-19) cells. The BMs entered ARPE-19 cells by endocytosis after a 6-h incubation and displayed much lower cytotoxicity than chemically synthesized magnetic nanoparticles (MNPs). MNPs exhibited significantly higher genotoxicity than BMs and promoted the expression of Bax (the programmed cell death acceleration protein) and the induction of greater cell necrosis. In BM-treated cells, apoptosis tended to be suppressed via increased expression of the Bcl-2 protein. In conclusion, BMs display excellent biocompatibility and potential for use in the treatment of ocular diseases.

  6. Generation of Distal Airway Epithelium from Multipotent Human Foregut Stem Cells.

    Science.gov (United States)

    Hannan, Nicholas R F; Sampaziotis, Fotios; Segeritz, Charis-Patricia; Hanley, Neil A; Vallier, Ludovic

    2015-07-15

    Collectively, lung diseases are one of the largest causes of premature death worldwide and represent a major focus in the field of regenerative medicine. Despite significant progress, only few stem cell platforms are currently available for cell-based therapy, disease modeling, and drug screening in the context of pulmonary disorders. Human foregut stem cells (hFSCs) represent an advantageous progenitor cell type that can be used to amplify large quantities of cells for regenerative medicine applications and can be derived from any human pluripotent stem cell line. Here, we further demonstrate the application of hFSCs by generating a near homogeneous population of early pulmonary endoderm cells coexpressing NKX2.1 and FOXP2. These progenitors are then able to form cells that are representative of distal airway epithelium that express NKX2.1, GATA6, and cystic fibrosis transmembrane conductance regulator (CFTR) and secrete SFTPC. This culture system can be applied to hFSCs carrying the CFTR mutation Δf508, enabling the development of an in vitro model for cystic fibrosis. This platform is compatible with drug screening and functional validations of small molecules, which can reverse the phenotype associated with CFTR mutation. This is the first demonstration that multipotent endoderm stem cells can differentiate not only into both liver and pancreatic cells but also into lung endoderm. Furthermore, our study establishes a new approach for the generation of functional lung cells that can be used for disease modeling as well as for drug screening and the study of lung development.

  7. A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium

    Directory of Open Access Journals (Sweden)

    Sparrow Malcolm P

    2005-10-01

    Full Text Available Abstract Background Pulmonary neuroendocrine cells (PNEC are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribution, and their relationship to the epithelial nerves in whole mounts of adult human bronchi using confocal microscopy. Methods Bronchi were resected from non-diseased portions of a lobe of human lung obtained from 8 thoracotomy patients (Table 1 undergoing surgery for the removal of lung tumors. Whole mounts were stained with antibodies to reveal all nerves (PGP 9.5, sensory nerves (calcitonin gene related peptide, CGRP, and PNEC (PGP 9.5, CGRP and gastrin releasing peptide, GRP. The analysis and rendition of the resulting three-dimensional data sets, including side-projections, was performed using NIH-Image software. Images were colorized and super-imposed using Adobe Photoshop. Results PNEC were abundant but not homogenously distributed within the epithelium, with densities ranging from 65/mm2 to denser patches of 250/mm2, depending on the individual wholemount. Rotation of 3-D images revealed a complex morphology; flask-like with the cell body near the basement membrane and a thick stem extending to the lumen. Long processes issued laterally from its base, some lumenal and others with feet-like processes. Calcitonin gene-related peptide (CGRP was present in about 20% of PNEC, mainly in the processes. CGRP-positive nerves were sparse, with some associated with the apical part of the PNEC. Conclusion Our 3D-data demonstrates that PNEC are numerous and exhibit a heterogeneous peptide content suggesting an active and diverse PNEC population.

  8. Correspondence regarding "Effect of active smoking on the human bronchial epithelium transcriptome"

    Directory of Open Access Journals (Sweden)

    Zuyderduyn Scott D

    2009-02-01

    Full Text Available Abstract Background In the work of Chari et al. entitled "Effect of active smoking on the human bronchial epithelium transcriptome" the authors use SAGE to identify candidate gene expression changes in bronchial brushings from never, former, and current smokers. These gene expression changes are categorized into those that are reversible or irreversible upon smoking cessation. A subset of these identified genes is validated on an independent cohort using RT-PCR. The authors conclude that their results support the notion of gene expression changes in the lungs of smokers which persist even after an individual has quit. Results This correspondence raises questions about the validity of the approach used by the authors to analyze their data. The majority of the reported results suffer deficiencies due to the methods used. The most fundamental of these are explained in detail: biases introduced during data processing, lack of correction for multiple testing, and an incorrect use of clustering for gene discovery. A randomly generated "null" dataset is used to show the consequences of these shortcomings. Conclusion Most of Chari et al.'s findings are consistent with what would be expected by chance alone. Although there is clear evidence of reversible changes in gene expression, the majority of those identified appear to be false positives. However, contrary to the authors' claims, no irreversible changes were identified. There is a broad consensus that genetic change due to smoking persists once an individual has quit smoking; unfortunately, this study lacks sufficient scientific rigour to support or refute this hypothesis or identify any specific candidate genes. The pitfalls of large-scale analysis, as exemplified here, may not be unique to Chari et al.

  9. Analysis of clonal expansions through the normal and premalignant human breast epithelium reveals the presence of luminal stem cells.

    Science.gov (United States)

    Cereser, Biancastella; Jansen, Marnix; Austin, Emily; Elia, George; McFarlane, Taneisha; van Deurzen, Carolien Hm; Sieuwerts, Anieta M; Daidone, Maria G; Tadrous, Paul J; Wright, Nicholas A; Jones, Louise; McDonald, Stuart Ac

    2018-01-01

    It is widely accepted that the cell of origin of breast cancer is the adult mammary epithelial stem cell; however, demonstrating the presence and location of tissue stem cells in the human breast has proved difficult. Furthermore, we do not know the clonal architecture of the normal and premalignant mammary epithelium or its cellular hierarchy. Here, we use deficiency in the mitochondrial enzyme cytochrome c oxidase (CCO), typically caused by somatic mutations in the mitochondrial genome, as a means to perform lineage tracing in the human mammary epithelium. PCR sequencing of laser-capture microdissected cells in combination with immunohistochemistry for markers of lineage differentiation was performed to determine the clonal nature of the mammary epithelium. We have shown that in the normal human breast, clonal expansions (defined here by areas of CCO deficiency) are typically uncommon and of limited size, but can occur at any site within the adult mammary epithelium. The presence of a stem cell population was shown by demonstrating multi-lineage differentiation within CCO-deficient areas. Interestingly, we observed infrequent CCO deficiency that was restricted to luminal cells, suggesting that niche succession, and by inference stem cell location, is located within the luminal layer. CCO-deficient areas appeared large within areas of ductal carcinoma in situ, suggesting that the rate of clonal expansion was altered in the premalignant lesion. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  10. The human gastrointestinal microbiota - An unexplored frontier for pharmaceutical discovery

    NARCIS (Netherlands)

    Roeselers, G.; Bouwman, J.; Venema, K.; Montijn, R.

    2012-01-01

    The mammalian gastrointestinal tract (GIT) harbors microorganisms (the microbiota) of vast phylogentic, genomic, and metabolic diversity, and recent years have seen a rapid development in the techniques for studying these complex microbial ecosystems. It is increasingly apparent that the GIT

  11. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability.

    Science.gov (United States)

    Boretto, Matteo; Cox, Benoit; Noben, Manuel; Hendriks, Nikolai; Fassbender, Amelie; Roose, Heleen; Amant, Frédéric; Timmerman, Dirk; Tomassetti, Carla; Vanhie, Arne; Meuleman, Christel; Ferrante, Marc; Vankelecom, Hugo

    2017-05-15

    The endometrium, which is of crucial importance for reproduction, undergoes dynamic cyclic tissue remodeling. Knowledge of its molecular and cellular regulation is poor, primarily owing to a lack of study models. Here, we have established a novel and promising organoid model from both mouse and human endometrium. Dissociated endometrial tissue, embedded in Matrigel under WNT-activating conditions, swiftly formed organoid structures that showed long-term expansion capacity, and reproduced the molecular and histological phenotype of the tissue's epithelium. The supplemented WNT level determined the type of mouse endometrial organoids obtained: high WNT yielded cystic organoids displaying a more differentiated phenotype than the dense organoids obtained in low WNT. The organoids phenocopied physiological responses of endometrial epithelium to hormones, including increased cell proliferation under estrogen and maturation upon progesterone. Moreover, the human endometrial organoids replicated the menstrual cycle under hormonal treatment at both the morpho-histological and molecular levels. Together, we established an organoid culture system for endometrium, reproducing tissue epithelium physiology and allowing long-term expansion. This novel model provides a powerful tool for studying mechanisms underlying the biology as well as the pathology of this key reproductive organ. © 2017. Published by The Company of Biologists Ltd.

  12. [Quantitative image analysis in pulmonary pathology - digitalization of preneoplastic lesions in human bronchial epithelium (author's transl)].

    Science.gov (United States)

    Steinbach, T; Müller, K M; Kämper, H

    1979-01-01

    The report concerns the first phase of a quantitative study of normal and abnormal bronchial epithelium with the objective of establishing the digitalization of histologic patterns. Preparative methods, data collecting and handling, and further mathematical analysis are described. In cluster and discriminatory analysis the digitalized histologic features can be used to separate and classify the individual cases into the respective diagnostic groups.

  13. Expression of Toll-like receptor 9 and response to bacterial CpG oligodeoxynucleotides in human intestinal epithelium

    DEFF Research Database (Denmark)

    Pedersen, G; Andresen, Lars; Matthiessen, M W

    2005-01-01

    Recognition of repeat CpG motifs, which are common in bacterial, but not in mammalian, DNA, through Toll-like receptor (TLR)9 is an integral part of the innate immune system. As the role of TLR9 in the human gut is unknown, we determined the spectrum of TLR9 expression in normal and inflamed colo...... in vitro despite spontaneous TLR9 gene expression. This suggests that the human epithelium is able to avoid inappropriate immune responses to luminal bacterial products through modulation of the TLR9 pathway....

  14. Epigenetic silencing of MAL, a putative tumor suppressor gene, can contribute to human epithelium cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang Jun

    2010-11-01

    Full Text Available Abstract Background To identify new and useful candidate biomarkers in head and neck squamous cell carcinoma (HNSCC, we performed a genome-wide survey and found that Myelin and lymphocyte-associated protein (MAL was a gene that was markedly down-regulated in HNSCC. Hence, we investigated the mechanism of MAL silencing and the effects of MAL on the proliferation, invasion, and apoptotic potential in HNSCC. Results MAL was significantly down-regulated in 91.7% of HNSCC specimens at the mRNA level as compared with adjacent normal tissues (P = 0.0004. Moreover, the relative transcript levels of the MAL gene were remarkably decreased by five-fold in nine HNSCC cell lines as compared with normal head and neck epithelium cells. MAL gene expression was restored in 44%, 67%, and 89% in HNSCC cell lines treated with TSA, 5-Aza-dC, and TSA plus 5-Aza-dC, respectively. Furthermore, bisulfate-treated DNA sequencing demonstrated that the two CpG islands (that is, M1 and M2 located in MAL promoter region were completely methylated in the HNSCC cell lines (CpG methylated ratio was more than 90%, and only one CpG island (that is, M1 was partially methylated in HNSCC tissues (CpG methylated ratio between 20% and 90%. A significant reduction in cell proliferation and a change in the cell cycle profile were also observed in MAL transfectants. Matrigel assay demonstrated that the invasiveness of HNSCC cells significantly decreased. A significant increase in the population of apoptotic cells was observed in MAL transfected cells. The exogenous expression of the MAL gene suppressed malignant phenotypes, while the cell death induced by MAL gene transfer was a result of apoptosis as demonstrated by the induction of cleavage of the poly (that is, ADP-ribose polymerase. Additionally, tumor growth was suppressed in cells expressing MAL as compared with cells not expressing MAL. Conclusion Our data suggest that the epigenetic inactivation of MAL, as a candidate tumor

  15. Bioinspired onion epithelium-like structure promotes the maturation of cardiomyocytes derived from human pluripotent stem cells.

    Science.gov (United States)

    Xu, Cong; Wang, Li; Yu, Yue; Yin, Fangchao; Zhang, Xiaoqing; Jiang, Lei; Qin, Jianhua

    2017-08-22

    Organized cardiomyocyte alignment is critical to maintain the mechanical properties of the heart. In this study, we present a new and simple strategy to fabricate a biomimetic microchip designed with an onion epithelium-like structure and investigate the guided behavior of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) on the substrate. The hiPSC-CMs were observed to be confined by the three dimensional surficial features morphologically, analogous to the in vivo microenvironment, and exhibited an organized anisotropic alignment on the onion epithelium-like structure with good beating function. The calcium imaging of hiPSC-CMs demonstrated a more mature Ca 2+ spark pattern as well. Furthermore, the expression of sarcomere genes (TNNI3, MYH6 and MYH7), potassium channel genes (KCNE1 and KCNH2), and calcium channel genes (RYR2) was significantly up-regulated on the substrate with an onion epithelium-like structure instead of the surface without the structure, indicating a more matured status of cardiomyocytes induced by this structure. It appears that the biomimetic micropatterned structure, analogous to in vivo cellular organization, is an important factor that might promote the maturation of hiPSC-CMs, providing new biological insights to guide hiPSC-CM maturation by biophysical factors. The established approach may offer an effective in vitro model for investigating cardiomyocyte differentiation, maturation and tissue engineering applications.

  16. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

    Science.gov (United States)

    Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2016-06-01

    Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

  17. Hepatic metabolism of toluene after gastrointestinal uptake in humans

    DEFF Research Database (Denmark)

    Bælum, Jesper; Mølhave, Lars; Honoré Hansen, S

    1993-01-01

    The metabolism of toluene and the influence of small doses of ethanol were measured in eight male volunteers after gastrointestinal uptake, the toluene concentration in alveolar air and the urinary excretion of hippuric acid and ortho-cresol being used as the measures of metabolism. During toluene...

  18. Gastrointestinal osmoreceptors and renal sodium excretion in humans

    DEFF Research Database (Denmark)

    Andersen, L.J.; Jensen, T.U.; Bestle, M.H.

    2000-01-01

    The hypothesis that natriuresis can be induced by stimulation of gastrointestinal osmoreceptors was tested in eight supine subjects on constant sodium intake (150 mmol NaCl/day). A sodium load equivalent to the amount contained in 10% of measured extracellular volume was administered by a nasogas......-angiotensin system....

  19. A breakdown in communication? Understanding the effects of aging on the human small intestine epithelium

    OpenAIRE

    Mabbott, Neil A.

    2015-01-01

    In the intestine, a single layer of epithelial cells sealed together at their apical surfaces by tight junctions helps to prevent the luminal commensal and pathogenic micro-organisms and their toxins from entering host tissues. The intestinal epithelium also helps to maintain homoeostasis in the mucosal immune system by expressing anti-inflammatory cytokines in the steady state and inflammatory cytokines in response to pathogens. Although the function of the mucosal immune system is impaired ...

  20. Avian Influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways.

    Directory of Open Access Journals (Sweden)

    Margaret A Scull

    2009-05-01

    Full Text Available Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE, we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37 degrees C, avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human proximal airways (32 degrees C. These data support the hypothesis that avian influenza viruses, ordinarily adapted to the temperature of the avian enteric tract (40 degrees C, rarely infect humans, in part due to differences in host airway regional temperatures. Previously, a critical residue at position 627 in the avian influenza virus polymerase subunit, PB2, was identified as conferring temperature-dependency in mammalian cells. Here, we use reverse genetics to show that avianization of residue 627 attenuates a human virus, but does not account for the different infection between 32 degrees C and 37 degrees C. To determine the mechanism of temperature restriction of avian influenza viruses in HAE at 32 degrees C, we generated recombinant human influenza viruses in either the A/Victoria/3/75 (H3N2 or A/PR/8/34 (H1N1 genetic background that contained avian or avian-like glycoproteins. Two of these viruses, A/Victoria/3/75 with L226Q and S228G mutations in hemagglutinin (HA and neuraminidase (NA from A/Chick/Italy/1347/99 and A/PR/8/34 containing the H7 and N1 from A/Chick/Italy/1347/99, exhibited temperature restriction approaching that of wholly avian influenza viruses. These data suggest that influenza viruses bearing avian or avian-like surface glycoproteins have a reduced capacity to establish productive infection at the temperature of the human proximal airways. This temperature restriction may limit zoonotic transmission of avian influenza viruses and

  1. Accumulation of 8-nitroguanine in human gastric epithelium induced by Helicobacter pylori infection

    International Nuclear Information System (INIS)

    Ma, Ning; Adachi, Yukihiko; Hiraku, Yusuke; Horiki, Noriyuki; Horiike, Shinichirou; Imoto, Ichiro; Pinlaor, Somchai; Murata, Mariko; Semba, Reiji; Kawanishi, Shosuke

    2004-01-01

    Helicobacter pylori infection causes chronic inflammation, which can lead to gastric carcinoma. A double immunofluorescence labeling study demonstrated that the level of 8-nitroguanine and 8-oxo-7,8-dihydro-2 ' -deoxyguanosine (8-oxodG) apparent in gastric gland epithelium was significantly higher in gastritis patients with H. pylori infection than in those without infection. A significant accumulation of proliferating cell nuclear antigen, a prognostic factor for gastric cancer, was observed in gastric gland epithelial cells in patients with H. pylori infection as compared to those without infection, and its accumulation was closely correlated with the formation of 8-nitroguanine and 8-oxodG. These results suggest that nitrosative and oxidative DNA damage in gastric epithelial cells and their proliferation by H. pylori infection may lead to gastric carcinoma. 8-Nitroguanine could be not only a promising biomarker for inflammation but also a useful indicator of the risk of gastric cancer development in response to chronic H. pylori infection

  2. The effects of human serum to the morphology, proliferation and gene expression level of the respiratory epithelium in vitro.

    Science.gov (United States)

    Yunus, Mohd Heikal Mohd; Siang, Kan Chan; Hashim, Nurul Izzati; Zhi, Ng Pei; Zamani, Nur Fathurah; Sabri, Primuharsa Putra; Busra, Mohd Fauzi; Chowdhury, Shiplu Roy; Idrus, Ruszymah Binti Haji

    2014-08-01

    The culture of human airway epithelial cells has played an important role in advancing our understanding of the metabolic and molecular mechanisms underlying normal function and disease pathology of airway epithelial cells. The present study focused on investigating the effects of human serum (HS) on the qualitative and quantitative properties of the human respiratory epithelium compared to the fetal bovine serum (FBS), as a supplement in culture. Respiratory epithelial (RE) cells derived from human nasal turbinate were co-cultured with fibroblasts, subsequently separated at 80-90% confluency by differential trypsinization. RE cells were then sub-cultured into 2 different plates containing 5% allogenic HS and FBS supplemented media respectively up to passage 1 (P1). Cell morphology, growth rate, cell viability and population doubling time were assessed under light microscope, and levels of gene expression were measured via real time reverse transcriptase-polymerase chain reaction (qRT-PCR). RE cells appeared as polygonal shape and expanded when cultured in HS whereas RE cells in FBS were observed to be easily matured thus limit the RE cells expansion. Proliferation rate of RE cells in HS supplemented media (7673.18 ± 1207.15) was 3 times higher compared to RE in FBS supplemented media (2357.68 ± 186.85). Furthermore, RE cells cultured in HS-supplemented media required fewer days (9.15 ± 1.10) to double in numbers compared to cells cultured in FBS-supplemented media (13.66 ± 0.81). Both the differences were significant (p0.05). In conclusion, HS is a comparatively better choice of media supplement in accelerating growth kinetics of RE cells in vitro thus producing a better quality of respiratory epithelium for future tracheal reconstruction. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Cytotoxicity of nano-hydroxyapatite on human-derived oral epithelium cell line: an in vitro study

    Directory of Open Access Journals (Sweden)

    Farid Abassi

    2016-08-01

    Full Text Available Background: Hydroxyapatite nanoparticles have a more surface contact and solubility than conventional hydroxyapatite. Hydroxynanoparticles enhances the biological and mechanical properties of new regenerated tissues. The hydroxyapatite nanoparticles have received attention as a new and effective osseous graft for using as scaffolds in bone regeneration. The reports on hydroxyapatite nanoparticles biocompatibility are controversial. It has been shown that hydroxyapatite nanoparticles induces inflammatory reaction and apoptosis. The aim of the present study was to evaluate the cytotoxicity of nano-hydroxyapatite on the human epithelial cells. Methods: The study was experimental and completed in vitro. The study was carried out in department of Immonulogy, Faculty of Medicine, Shahid Beheshti University of Medical Sciences in November 2014. The human-derived oral epithelium cell line (KB obtained from Pasteur Institute, Tehran, Iran were exposed to hydroxyapatite nanoparticles at 0.01, 0.05, 0.1, 0.5, 0.75, 1, 2.5 and 5 mg/ml concentrations in 24, 48 and 72 hours. Rod-shaped hydroxyapatite nanoparticles with 99% purity and maximum 100 nm sized particles were used. Methylthiazol tetrazolium bromide (MTT method was employed for cell vitality evaluation. Enzyme-linked immunosorbent assay (ELISA was used for assessing the viability of cells. Distilled water and fetal bovine serum (FBS were positive and negative controls. ANOVA and Duncan tests were used for statistical analysis. Results: The cytotoxicity of different concentrations of hydroxyapatite nanoparticles on human-derived oral epithelium cell line in 24 (P< 0.001, 48 (P< 0.001 and 72 hours (P< 0.001 was significantly different. The nano-hydroxyapatite particles at 0.5 to 1 mg/ml had the highest cytotoxicity effect on human-derived oral epithelium cells in 24, 48 and 72 hours. Lower concentrations than 0.05 mg/ml had the best biocompatibility properties in 24, 48 and 72 hours. Conclusion

  4. Three-dimensional neuroepithelial culture from human embryonic stem cells and its use for quantitative conversion to retinal pigment epithelium.

    Directory of Open Access Journals (Sweden)

    Yu Zhu

    Full Text Available A goal in human embryonic stem cell (hESC research is the faithful differentiation to given cell types such as neural lineages. During embryonic development, a basement membrane surrounds the neural plate that forms a tight, apico-basolaterally polarized epithelium before closing to form a neural tube with a single lumen. Here we show that the three-dimensional epithelial cyst culture of hESCs in Matrigel combined with neural induction results in a quantitative conversion into neuroepithelial cysts containing a single lumen. Cells attain a defined neuroepithelial identity by 5 days. The neuroepithelial cysts naturally generate retinal epithelium, in part due to IGF-1/insulin signaling. We demonstrate the utility of this epithelial culture approach by achieving a quantitative production of retinal pigment epithelial (RPE cells from hESCs within 30 days. Direct transplantation of this RPE into a rat model of retinal degeneration without any selection or expansion of the cells results in the formation of a donor-derived RPE monolayer that rescues photoreceptor cells. The cyst method for neuroepithelial differentiation of pluripotent stem cells is not only of importance for RPE generation but will also be relevant to the production of other neuronal cell types and for reconstituting complex patterning events from three-dimensional neuroepithelia.

  5. Molecular mechanism of ocular surface damage: application to an in vitro dry eye model on human corneal epithelium.

    Science.gov (United States)

    Meloni, Marisa; De Servi, Barbara; Marasco, Daniela; Del Prete, Salvatore

    2011-01-12

    The present study was concerned with the development of a new experimental model of dry eye using human reconstructed in vitro corneal epithelium (HCE). The model is based on the use of adapted culture conditions that induce relevant modifications at the cellular and molecular level thus mimicking dry eye. The HCE model was maintained in a controlled environmental setting (relative humidity eye. The evolution of the dry eye condition was assessed by histology, immunohistochemistry staining, scanning electron microscopy, and gene expression by using TaqMan gene assay technology (mucin-4 [MUC4], matrix metallopeptidase-9 [MMP9], tumor necrosis factor-α [TNF-α], and defensin β-2 [DEFB2). The effects of different commercially available tear substitutes on the induced dry eye condition were tested. This in vitro dry eye HCE model, that was well established within 24 h, has the characteristic features of a dry eye epithelium and could be satisfactorily used for preliminary assessment of the protective activity of some artificial tears. The transcriptional study of selected biomarkers showed an increase in MUC4, MMP9, TNF-α, and hBD-2 (DEFB2) gene expression. By using a dynamic approach, we were able to define a biomarker gene signature of dry eye-induced effects that could be predictive of corneal damage in vivo and to discriminate the efficacy among different commercial artificial tears.

  6. Determination of ABO blood grouping from human oral squamous epithelium by the highly sensitive immunohistochemical staining method EnVision+.

    Science.gov (United States)

    Noda, Hiroshi; Yokota, Makoto; Tatsumi, Shinji; Sugiyama, Shizuyuki

    2002-03-01

    Using the highly sensitive immunohistochemical staining method EnVision+, which employs a dextran polymer reagent for the secondary antibody, the detection of the ABH antigens was attempted in the oral squamous epithelium. This new technique uses monoclonal antibody as a primary antibody and it takes about three hours for staining. The time is much shorter than conventional absorption-elution testing or absorption-inhibition testing for the determination of ABO blood grouping. Secretor saliva samples were stained at strong intensity by the antibody, which corresponded to its blood group and anti-H. On the one hand, nonsecretor saliva samples were stained at strong intensity only by the antibody that corresponded to its blood group, and at weak intensity only by anti-H. Since human oral squamous epithelium antigens were stained specifically by this method, we can examine the ABO blood group of saliva samples and perform cytodiagnosis at the same time. Our research suggested that the EnVision+ Method is a useful technique for ABO blood grouping of saliva in forensic cases.

  7. Progenitor Epithelium

    Science.gov (United States)

    Marty-Santos, Leilani

    2015-01-01

    Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell–cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. PMID:26216134

  8. Levcromakalim- and isoprenaline-induced relaxation of human isolated airways--role of the epithelium and of K+ channel activation.

    Science.gov (United States)

    Black, J L; Johnson, P R; McKay, K O; Carey, D; Armour, C L

    1994-06-01

    In this study we have investigated the mechanism of action of levcromakalim and isoprenaline in human isolated airways with respect to the K+ channels they activate and the possibility that these smooth muscle relaxants activate K+ channels on the airway epithelium. Mechanical removal of the epithelial layer (mean percentage of epithelium present 20 +/- 3%, n = 20 tissues) did not affect the relaxation responses to levcromakalim or isoprenaline, either in terms of maximal relaxation or sensitivity. Whilst having no effect on isoprenaline-induced relaxation, studied from basal tone, the ATP-sensitive K+ channel blocker BRL 31660 (10, 30 and 50 microM) reduced relaxation responses induced (from basal tone) by levcromakalim from 74 +/- 6% (of the maximal response to isoprenaline) to 48 +/- 12% (n = 7), 9 +/- 9% (n = 4) and 0 (n = 4), respectively. Charybdotoxin, a blocker of high conductance Ca(2+)-activated K+ channels, at concentrations of 30 and 100 nM, had no effect on either levcromakalim- or or isoprenaline-induced relaxation responses and yet charybdotoxin was active at KCa channels in outside-out patches of hippocampal granule cells. Moreover, tetraethylammonium (10 mM) inhibited neither isoprenaline- nor levcromakalim-induced relaxation. This study has demonstrated that the relaxation responses elicited in human bronchus to isoprenaline and levcromakalim are likely to be the result of direct effects on the smooth muscle with no contribution from epithelial receptors or K+ channels. The actions of levcromakalim appear to be mediated only via activation of KATP channels. Further, we have made the important observation that, under the experimental conditions of our study, isoprenaline does not activate the KCa channel to produce relaxation in human bronchus.

  9. The functionality of the gastrointestinal microbiome in non-human animals.

    Science.gov (United States)

    Hanning, Irene; Diaz-Sanchez, Sandra

    2015-11-10

    Due to the significance of the microbiome on human health, much of the current data available regarding microbiome functionality is centered on human medicine. For agriculturally important taxa, the functionality of gastrointestinal bacteria has been studied with the primary goals of improving animal health and production performance. With respect to cattle, the digestive functions of bacteria in cattle are unarguably critical to digestion and positively impact production performance. Conversely, some research suggests that the gastrointestinal microbiome in chickens competes with the host for nutrients and produces toxins that can harm the host resulting in decreased growth efficiency. Concerning many other species including reptiles and cetaceans, some cataloging of fecal bacteria has been conducted, but the functionality within the host remains ambiguous. These taxa could provide interesting gastrointestinal insight into functionality and symbiosis considering the extreme feeding regimes (snakes), highly specialized diets (vampire bats), and living environments (polar bears), which warrants further exploration.

  10. Caveolin-1 as a novel indicator of wound-healing capacity in aged human corneal epithelium.

    Science.gov (United States)

    Rhim, Ji Heon; Kim, Jae Hoon; Yeo, Eui-Ju; Kim, Jae Chan; Park, Sang Chul

    2010-01-01

    Excess caveolin-1 has been reported to play a role in age-dependent hyporesponsiveness to growth factors in vitro. Therefore, we hypothesized that caveolin-1-dependent hyporesponsiveness to growth factors in aged corneal epithelial cells might be responsible for delayed wound healing in vivo. To test this hypothesis, we evaluated corneal wound-healing time by vital staining using fluorescein after laser epithelial keratomileusis (LASEK). We compared wound-healing times in young, middle-aged and elderly patients. We also examined caveolin-1 levels and other aging markers, such as p53 and p21, in the corneal epithelium. Elderly patients generally had higher caveolin-1 levels in the corneal epithelia than young patients. There were, however, variations among individuals with increased caveolin-1 in some young patients and decreased levels in some elderly patients. Wound-healing time after LASEK correlated well with the corneal caveolin-1 status. Therefore, we suggest that caveolin-1 status might be responsible for delayed wound healing in elderly patients after LASEK. Caveolin-1 status might be a regulator for wound-healing capacity and a novel target for in vivo adjustment.

  11. Gastrointestinal absorption of neptunium and curium in humans

    International Nuclear Information System (INIS)

    Popplewell, D.S.; Harrison, J.D.; Ham, G.J.

    1991-01-01

    The gastrointestinal absorption of Np and Cm has been determined in five male adult volunteers. The Np and Cm, which were in citrate solution, were taken with food. An initial experiment with each individual determined the fraction of each element excreted in the urine following intravenous administration. Subsequently, the results for urinary excretion for the two routes of administration were used to calculate the fractional absorption (f1) of ingested Np and Cm. The mean f1 values were: Np (2.0 +/- 0.2) X 10 - 4 , range (1.2-2.9) X 10 - 4 , and Cm (1.7 +/- 0.3) X 10 - 4 , range (0.95-3.0) X 10 - 4 , the quoted uncertainties being the standard error of the means. Currently, the International Commission on Radiological Protection recommends a value of 10 - 3 for both elements. Cumulative urinary excretion over 1 wk after intravenous injection accounted for about 20%-40% of administered Np and 7%-10% of Cm. At the conclusion of the experiment, the total committed effective dose equivalent for each volunteer was calculated to be in the range 130-250 microSv, based on the individual f1 values, and, in some cases, a knowledge of the rate of clearance of 239 Np through the gut as measured by whole-body counting

  12. Gastrointestinal Physiology During Head Down Tilt Bedrest in Human Subjects

    Science.gov (United States)

    Vaksman, Z.; Guthienz, J.; Putcha, L.

    2008-01-01

    Introduction: Gastrointestinal (GI) motility plays a key role in the physiology and function of the GI tract. It directly affects absorption of medications and nutrients taken by mouth, in addition to indirectly altering GI physiology by way of changes in the microfloral composition and biochemistry of the GI tract. Astronauts have reported nausea, loss of appetite and constipation during space flight all of which indicate a reduction in GI motility and function similar to the one seen in chronic bed rest patients. The purpose of this study is to determine GI motility and bacterial proliferation during -6 degree head down tilt bed rest (HTD). Methods: Healthy male and female subjects between the ages of 25-40 participated in a 60 day HTD study protocol. GI transit time (GITT) was determined using lactulose breath hydrogen test and bacterial overgrowth was measured using glucose breath hydrogen test. H. Pylori colonization was determined using C13-urea breath test (UBIT#). All three tests were conducted on 9 days before HDT, and repeated on HDT days 2, 28, 58, and again on day 7 after HDT. Results: GITT increased during HTD compared to the respective ambulatory control values; GITT was significantly lower on day 7 after HTD. A concomitant increase in bacterial colonization was also noticed during HDT starting after approximately 28 days of HDT. However, H. Pylori proliferation was not recorded during HDT as indicated by UBIT#. Conclusion: GITT significantly decreased during HDT with a concomitant increase in the proliferation of GI bacterial flora but not H. pylori.

  13. Uranium gastrointestinal absorption: the F1 factor in humans

    International Nuclear Information System (INIS)

    Zamora, M.L.; Zielinski, J.M.; Meyerhof, D.; Moodie, G.; Falcomer, R.; Tracy, B.

    2003-01-01

    The present investigation was undertaken by the Department of Health, Canada, to determine the most appropriate value to use for uranium gastrointestinal absorption (f 1 ) in setting the guideline for drinking water. Fifty participants, free from medical problems, were recruited from two communities: a rural area where drinking water, supplied from drilled wells, contained elevated levels of uranium and an urban area where the water supplied by the municipal water system contained -1 . Uranium intake through food, drinking water and other beverages was monitored using the duplicate diet approach. Intake and excretion were measured by inductively coupled plasma-mass spectrometry (ICP-MS) in samples collected concurrently from the same individuals over a 3 d period. The range of f 1 values was between 0.001 to 0.06, with a median of 0.009. These values were independent of gender, age, duration of exposure, daily total uranium intake and allocation of intake between food and water. Consistent with the recommendation of ICRP Publication 69, 78% were below 0.02. (author)

  14. Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans

    DEFF Research Database (Denmark)

    Falkén, Y; Hellström, P M; Sanger, G J

    2010-01-01

    Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis...... during a 6-h infusion in humans....

  15. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    Energy Technology Data Exchange (ETDEWEB)

    Manceur, Aziza P. [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Tseng, Michael [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Holowacz, Tamara [Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Witterick, Ian [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Department of Otolaryngology, Head and Neck Surgery, University of Toronto, ON (Canada); Weksberg, Rosanna [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); McCurdy, Richard D. [The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); Warsh, Jerry J. [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Audet, Julie, E-mail: julie.audet@utoronto.ca [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada)

    2011-09-10

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  16. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    International Nuclear Information System (INIS)

    Manceur, Aziza P.; Tseng, Michael; Holowacz, Tamara; Witterick, Ian; Weksberg, Rosanna; McCurdy, Richard D.; Warsh, Jerry J.; Audet, Julie

    2011-01-01

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  17. Amiodarone increases the accumulation of DEA in a human alveolar epithelium-derived cell line.

    Science.gov (United States)

    Seki, Satoru; Itagaki, Shirou; Kobayashi, Masaki; Hirano, Takeshi; Iseki, Ken

    2008-07-01

    Amiodarone (AMD)-induced pulmonary toxicity (AIPT) is the most life-threatening side-effect of AMD treatment. N-Monodesethylamiodarone (DEA), an active metabolite of AMD, also exhibits cytotoxicity and tends to accumulate in the lung more intensively than AMD. In this study, we characterized the mechanism of DEA accumulation using A549 cells as a model of the alveolar epithelium. Typical ATP-depletion compounds caused an approximately 30% increase in the accumulation of DEA in A549 cells, although these effects were less than those in Caco-2 cells. Triiodothyronine (T(3)), which exhibited an inhibitory effect on DEA efflux in Caco-2 cells, did not affect the accumulation of DEA in A549 cells. On the other hand, 100 microM AMD caused an approximately 200% increase in DEA content in A549 cells, although AMD accumulation was not affected by 100 microM DEA. Since the reducing effect of AMD on cellular ATP levels and that of FCCP were similar, the mechanism by which DEA accumulation is increased by AMD might be different from the ATP-dependent DEA efflux mechanism. The decrease in cell viability by DEA in the presence of AMD (IC(50) value of DEA for A549 cell viability: 25.4+/-2.4 microM) was more pronounced than that by DEA alone (IC(50) value: 11.5+/-3.0 microM). This further DEA accumulation by AMD might be a factor responsible for the greater accumulation of DEA than that of AMD in the lung in long-term AMD-treated patients.

  18. Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers.

    Science.gov (United States)

    Li, Guang; Yu, Kai; Li, Fushuang; Xu, Kangping; Li, Jing; He, Shujin; Cao, Shousong; Tan, Guishan

    2014-04-28

    Hericium is a genus of mushrooms (fungus) in the Hericiaceae family. Hericium erinaceus (HE) has been used for the treatment of digestive diseases for over 2000 years in China. HE possesses many beneficial functions such as anticancer, antiulcer, antiinflammation and antimicrobial effects, immunomodulation and other activities. The aim of the studies was to evaluate the anticancer efficacy of two extracts (HTJ5 and HTJ5A) from the culture broth of HE against three gastrointestinal cancers such as liver, colorectal and gastric cancers in both of in vitro of cancer cell lines and in vivo of tumor xenografts and discover the active compounds. Two HE extracts (HTJ5 and HTJ5A) were used for the studies. For the study of chemical constituents, the HTJ5 and HTJ5A were separated using a combination of macroporous resin with silica gel, HW-40 and LH-20 chromatography then purified by semipreparative high-performance liquid chromatography (HPLC) and determined by nuclear magnetic resonance (NMR) spectra. For the in vitro cytotoxicity studies, HepG2 and Huh-7 liver, HT-29 colon, and NCI-87 gastric cancer cell lines were used and MTT assay was performed to determine the in vitro cytotoxicity. For in vivo antitumor efficacy and toxicity studies, tumor xenograft models of SCID mice bearing liver cancer HepG2 and Huh-7, colon cancer HT-29 and gastric cancer NCI-87 subcutaneously were used and the mice were treated with the vehicle control, HTJ5 and HTJ5A orally (500 and 1000 mg/kg/day) and compared to 5-fluorouraci (5-FU) at the maximum tolerated dose (MTD, 25-30 mg/kg/day) intraperitoneally daily for 5 days when the tumors reached about 180-200 mg (mm(3)). Tumor volumes and body weight were measured daily during the first 10 days and 2-3 times a week thereafter to assess the tumor growth inhibition, tumor doubling time, partial and complete tumor response and toxicity. Twenty-two compounds were obtained from the fractions of HTJ5/HTJ5A including seven cycli dipeptides, five

  19. MicroRNA Expression Profiling of Human Respiratory Epithelium Affected by Invasive Candida Infection.

    Directory of Open Access Journals (Sweden)

    Syed Aun Muhammad

    Full Text Available Invasive candidiasis is potentially life-threatening systemic fungal infection caused by Candida albicans (C. albicans. Candida enters the blood stream and disseminate throughout the body and it is often observed in hospitalized patients, immunocompromised individuals or those with chronic diseases. This infection is opportunistic and risk starts with the colonization of C. albicans on mucocutaneous surfaces and respiratory epithelium. MicroRNAs (miRNAs are small non-coding RNAs which are involved in the regulation of virtually every cellular process. They regulate and control the levels of mRNA stability and post-transcriptional gene expression. Aberrant expression of miRNAs has been associated in many disease states, and miRNA-based therapies are in progress. In this study, we investigated possible variations of miRNA expression profiles of respiratory epithelial cells infected by invasive Candida species. For this purpose, respiratory epithelial tissues of infected individuals from hospital laboratory were accessed before their treatment. Invasive Candida infection was confirmed by isolation of Candia albicans from the blood cultures of the same infected individuals. The purity of epithelial tissues was assessed by flow cytometry (FACSCalibur cytometer; BD Biosciences, Heidelberg, Germany using statin antibody (S-44. TaqMan quantitative real-time PCR (in a TaqMan Low Density Array format was used for miRNA expression profiling. MiRNAs investigated, the levels of expression of 55 miRNA were significantly altered in infected tissues. Some miRNAs showed dramatic increase (miR-16-1 or decrease of expression (miR-17-3p as compared to control. Gene ontology enrichment analysis of these miRNA-targeted genes suggests that Candidal infection affect many important biological pathways. In summary, disturbance in miRNA expression levels indicated the change in cascade of pathological processes and the regulation of respiratory epithelial functions

  20. Characterization of materials eliciting foreign body reaction in stapled human gastrointestinal anastomoses.

    Science.gov (United States)

    Lim, C B B; Goldin, R D; Darzi, A; Hanna, G B

    2008-08-01

    Staples are made of titanium, which elicits minimal tissue reaction. The authors have encountered foreign body reaction associated with stapled human gastrointestinal anastomoses, although the literature has no reports of this. The aim of this study was to identify the refractile foreign materials causing this reaction. Histological sections were taken from 14 gastrointestinal specimens from patients with a history of a stapled anastomosis within the specimen excised. These were reviewed by light and polarization microscopy. Scanning electron microscopy and energy dispersive X-ray analysis were carried out on these sections, staples and stapler cartridges used for gastrointestinal surgery. Foreign bodies rich in fluorine were found in three patients, and those rich in carbon in 12. Other elements identified included oxygen, calcium, sodium, potassium, magnesium, aluminium and silicon. One specimen was found to contain titanium with no surrounding foreign body reaction. Stapler cartridges contained carbon, oxygen, fluorine, calcium, sodium, potassium, magnesium, aluminium, silicon and traces of titanium. Staples were composed of pure titanium with some fibrous material on the surface containing elements found in stapler cartridges. The presence of foreign body reaction was confirmed in stapled human gastrointestinal anastomoses. The source of refractile materials eliciting this reaction was the stapler cartridges. (c) 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  1. Generation of Functional Thymic Epithelium from Human Embryonic Stem Cells that Supports Host T Cell Development

    OpenAIRE

    Parent, Audrey V.; Russ, Holger A.; Khan, Imran S.; LaFlam, Taylor N.; Metzger, Todd C.; Anderson, Mark S.; Hebrok, Matthias

    2013-01-01

    Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T cell development represents a promising approach to reach this goal; however, progress toward generating functional TECs has been limited. Here, we describe a robust in vitro method to direct differentiation of human embryonic stem cells (hESCs) into th...

  2. Culturing of respiratory viruses in well-differentiated pseudostratified human airway epithelium as a tool to detect unknown viruses

    Science.gov (United States)

    Jazaeri Farsani, Seyed Mohammad; Deijs, Martin; Dijkman, Ronald; Molenkamp, Richard; Jeeninga, Rienk E; Ieven, Margareta; Goossens, Herman; van der Hoek, Lia

    2015-01-01

    Background Currently, virus discovery is mainly based on molecular techniques. Here, we propose a method that relies on virus culturing combined with state-of-the-art sequencing techniques. The most natural ex vivo culture system was used to enable replication of respiratory viruses. Method Three respiratory clinical samples were tested on well-differentiated pseudostratified tracheobronchial human airway epithelial (HAE) cultures grown at an air–liquid interface, which resemble the airway epithelium. Cells were stained with convalescent serum of the patients to identify infected cells and apical washes were analyzed by VIDISCA-454, a next-generation sequencing virus discovery technique. Results Infected cells were observed for all three samples. Sequencing subsequently indicated that the cells were infected by either human coronavirus OC43, influenzavirus B, or influenzavirus A. The sequence reads covered a large part of the genome (52%, 82%, and 57%, respectively). Conclusion We present here a new method for virus discovery that requires a virus culture on primary cells and an antibody detection. The virus in the harvest can be used to characterize the viral genome sequence and cell tropism, but also provides progeny virus to initiate experiments to fulfill the Koch's postulates. PMID:25482367

  3. Multi-nucleate retinal pigment epithelium cells of the human macula exhibit a characteristic and highly specific distribution.

    Science.gov (United States)

    Starnes, Austin C; Huisingh, Carrie; McGwin, Gerald; Sloan, Kenneth R; Ablonczy, Zsolt; Smith, R Theodore; Curcio, Christine A; Ach, Thomas

    2016-01-01

    The human retinal pigment epithelium (RPE) is reportedly 3% bi-nucleated. The importance to human vision of multi-nucleated (MN)-RPE cells could be clarified with more data about their distribution in central retina. Nineteen human RPE-flatmounts (9 ≤ 51 years, 10 > 80 years) were imaged at 12 locations: 3 eccentricities (fovea, perifovea, near periphery) in 4 quadrants (superior, inferior, temporal, nasal). Image stacks of lipofuscin-attributable autofluorescence and phalloidin labeled F-actin cytoskeleton were obtained using a confocal fluorescence microscope. Nuclei were devoid of autofluorescence and were marked using morphometric software. Cell areas were approximated by Voronoi regions. Mean number of nuclei per cell among eccentricity/quadrant groups and by age were compared using Poisson and binominal regression models. A total of 11,403 RPE cells at 200 locations were analyzed: 94.66% mono-, 5.31% bi-, 0.02% tri-nucleate, and 0.01% with 5 nuclei. Age had no effect on number of nuclei. There were significant regional differences: highest frequencies of MN-cells were found at the perifovea (9.9%) and near periphery (6.8%). The fovea lacked MN-cells almost entirely. The nasal quadrant had significantly more MN-cells compared to other quadrants, at all eccentricities. This study demonstrates MN-RPE cells in human macula. MN-cells may arise due to endoreplication, cell fusion, or incomplete cell division. The topography of MN-RPE cells follows the topography of photoreceptors; with near-absence at the fovea (cones only) and high frequency at perifovea (highest rod density). This distribution might reflect specific requirements of retinal metabolism or other mechanisms addressable in further studies.

  4. Langerhans cells from human oral epithelium are more effective at stimulating allogeneic T cells in vitro than Langerhans cells from skin.

    Science.gov (United States)

    Hasséus, B; Jontell, M; Bergenholtz, G; Dahlgren, U I

    2004-06-01

    This report is focused on the functional capacity of Langerhans cells (LC) in the epithelium of skin and oral mucosa, which both meet different antigenic challenges. The capacity of LC from human oral and skin epithelium to provide co-stimulatory signals to T cells in vitro was compared. LC in a crude suspension of oral epithelial cells had a significantly enhanced T cell co-stimulatory capacity compared to skin epithelial cells. This applied both to cultures with concanavalin A (con-A)-stimulated syngeneic T cells and to a mixed epithelial cell lymphocyte reaction involving allogeneic T cells. The co-stimulatory capacity of oral and skin epithelial cells was reduced by >70% if monoclonal antibodies against HLA-DR, -DP and -DQ were added to the cultures with allogeneic T cells, indicating the involvement of HLA class II expressing LC. Immunohistochemistry revealed that 6% of the epithelial cells were CD1a + LC in sections from both oral and skin epithelium. Interleukin (IL)-8 production was higher in cultures of oral epithelial cells and con-A stimulated T cells than in corresponding cultures with skin epithelial cells as accessory cells. The results suggest that LC in human oral epithelium are more efficient at stimulating T cells than those of skin.

  5. Regulation of gene expression in human mammary epithelium: effect of breast pumping

    Science.gov (United States)

    Little is known of the molecular regulation of human milk production because of limitations in obtaining mammary tissue from lactating women. Our objectives were to evaluate whether RNA isolated from breast milk fat globules (MFGs) could be an alternative to mammary biopsies and to determine whether...

  6. Impact of pasteurization of human milk on preterm newborn in vitro digestion: Gastrointestinal disintegration, lipolysis and proteolysis.

    Science.gov (United States)

    de Oliveira, Samira C; Bourlieu, Claire; Ménard, Olivia; Bellanger, Amandine; Henry, Gwénaële; Rousseau, Florence; Dirson, Emelyne; Carrière, Frédéric; Dupont, Didier; Deglaire, Amélie

    2016-11-15

    Human milk feeding is an important recommendation for preterm newborns considering their vulnerability and digestive immaturity. Holder pasteurization (62.5°C, 30min) applied in milk banks modifies its biological quality and its microstructure. We investigated the impact of pasteurization of preterm human milk on its gastrointestinal kinetics of lipolysis, proteolysis and structural disintegration. An in vitro dynamic system was set up to simulate the gastrointestinal digestion of preterm newborns. A pool of preterm human milk was digested as raw or after Holder pasteurization. Pasteurization impacted the microstructure of undigested human milk, its gastrointestinal disintegration and tended to limit the intestinal lipolysis. Furthermore, the gastrointestinal bioaccessibility of some fatty acids was decreased by pasteurization, while the intestinal bioaccessibility of some amino acids was selectively modulated. The impact of pasteurization on the digestion of human milk may have nutritional relevance in vivo and potentially modulates preterm development and growth. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Lactotetraosylceramide, a novel glycosphingolipid receptor for Helicobacter pylori, present in human gastric epithelium

    OpenAIRE

    Teneberg, Susann; Leonardsson, Iréne; Karlsson, Hasse; Jovall, Per-Åke; Ångström, Jonas; Danielsson, Dan; Näslund, Ingmar; Ljungh, Åsa; Wadström, Torkel; Karlsson, Karl-Anders

    2002-01-01

    The binding of Helicobacter pylori to glycosphingolipids was examined by binding of 35S-labeled bacteria to glycosphingolipids on thin-layer chromatograms. In addition to previously reported binding specificities, a selective binding to a non-acid tetraglycosylceramide of human meconium was found. This H. pylori binding glycosphingolipid was isolated and, on the basis of mass spectrometry, proton NMR spectroscopy, and degradation studies, were identified as Gal3GlcNAc3Gal4Glc1Cer (lactotetrao...

  8. Anopheles Midgut Epithelium Evades Human Complement Activity by Capturing Factor H from the Blood Meal

    Science.gov (United States)

    Khattab, Ayman; Barroso, Marta; Miettinen, Tiera; Meri, Seppo

    2015-01-01

    Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood. PMID:25679788

  9. Anopheles midgut epithelium evades human complement activity by capturing factor H from the blood meal.

    Directory of Open Access Journals (Sweden)

    Ayman Khattab

    2015-02-01

    Full Text Available Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood.

  10. Generation of corneal epithelial cells from induced pluripotent stem cells derived from human dermal fibroblast and corneal limbal epithelium.

    Directory of Open Access Journals (Sweden)

    Ryuhei Hayashi

    Full Text Available Induced pluripotent stem (iPS cells can be established from somatic cells. However, there is currently no established strategy to generate corneal epithelial cells from iPS cells. In this study, we investigated whether corneal epithelial cells could be differentiated from iPS cells. We tested 2 distinct sources: human adult dermal fibroblast (HDF-derived iPS cells (253G1 and human adult corneal limbal epithelial cells (HLEC-derived iPS cells (L1B41. We first established iPS cells from HLEC by introducing the Yamanaka 4 factors. Corneal epithelial cells were successfully induced from the iPS cells by the stromal cell-derived inducing activity (SDIA differentiation method, as Pax6(+/K12(+ corneal epithelial colonies were observed after prolonged differentiation culture (12 weeks or later in both the L1B41 and 253G1 iPS cells following retinal pigment epithelial and lens cell induction. Interestingly, the corneal epithelial differentiation efficiency was higher in L1B41 than in 253G1. DNA methylation analysis revealed that a small proportion of differentially methylated regions still existed between L1B41 and 253G1 iPS cells even though no significant difference in methylation status was detected in the specific corneal epithelium-related genes such as K12, K3, and Pax6. The present study is the first to demonstrate a strategy for corneal epithelial cell differentiation from human iPS cells, and further suggests that the epigenomic status is associated with the propensity of iPS cells to differentiate into corneal epithelial cells.

  11. Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Keita, E-mail: uchino13@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Hirano, Gen [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Hirahashi, Minako [Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Isobe, Taichi; Shirakawa, Tsuyoshi; Kusaba, Hitoshi; Baba, Eishi [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Tsuneyoshi, Masazumi [Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Akashi, Koichi [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

    2012-09-10

    There is emerging evidence that human solid tumor cells originate from cancer stem cells (CSCs). In cancer cell lines, tumor-initiating CSCs are mainly found in the side population (SP) that has the capacity to extrude dyes such as Hoechst 33342. We found that Nanog is expressed specifically in SP cells of human gastrointestinal (GI) cancer cells. Nucleotide sequencing revealed that NanogP8 but not Nanog was expressed in GI cancer cells. Transfection of NanogP8 into GI cancer cell lines promoted cell proliferation, while its inhibition by anti-Nanog siRNA suppressed the proliferation. Immunohistochemical staining of primary GI cancer tissues revealed NanogP8 protein to be strongly expressed in 3 out of 60 cases. In these cases, NanogP8 was found especially in an infiltrative part of the tumor, in proliferating cells with Ki67 expression. These data suggest that NanogP8 is involved in GI cancer development in a fraction of patients, in whom it presumably acts by supporting CSC proliferation. -- Highlights: Black-Right-Pointing-Pointer Nanog maintains pluripotency by regulating embryonic stem cells differentiation. Black-Right-Pointing-Pointer Nanog is expressed in cancer stem cells of human gastrointestinal cancer cells. Black-Right-Pointing-Pointer Nucleotide sequencing revealed that Nanog pseudogene8 but not Nanog was expressed. Black-Right-Pointing-Pointer Nanog pseudogene8 promotes cancer stem cells proliferation. Black-Right-Pointing-Pointer Nanog pseudogene8 is involved in gastrointestinal cancer development.

  12. Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells

    International Nuclear Information System (INIS)

    Uchino, Keita; Hirano, Gen; Hirahashi, Minako; Isobe, Taichi; Shirakawa, Tsuyoshi; Kusaba, Hitoshi; Baba, Eishi; Tsuneyoshi, Masazumi; Akashi, Koichi

    2012-01-01

    There is emerging evidence that human solid tumor cells originate from cancer stem cells (CSCs). In cancer cell lines, tumor-initiating CSCs are mainly found in the side population (SP) that has the capacity to extrude dyes such as Hoechst 33342. We found that Nanog is expressed specifically in SP cells of human gastrointestinal (GI) cancer cells. Nucleotide sequencing revealed that NanogP8 but not Nanog was expressed in GI cancer cells. Transfection of NanogP8 into GI cancer cell lines promoted cell proliferation, while its inhibition by anti-Nanog siRNA suppressed the proliferation. Immunohistochemical staining of primary GI cancer tissues revealed NanogP8 protein to be strongly expressed in 3 out of 60 cases. In these cases, NanogP8 was found especially in an infiltrative part of the tumor, in proliferating cells with Ki67 expression. These data suggest that NanogP8 is involved in GI cancer development in a fraction of patients, in whom it presumably acts by supporting CSC proliferation. -- Highlights: ► Nanog maintains pluripotency by regulating embryonic stem cells differentiation. ► Nanog is expressed in cancer stem cells of human gastrointestinal cancer cells. ► Nucleotide sequencing revealed that Nanog pseudogene8 but not Nanog was expressed. ► Nanog pseudogene8 promotes cancer stem cells proliferation. ► Nanog pseudogene8 is involved in gastrointestinal cancer development.

  13. The Pathogenesis of Human Cervical Epithelium Cells Induced by Interacting with Trichomonas vaginalis

    Science.gov (United States)

    Lin, Wei-Chen; Chang, Wei-Ting; Chang, Tsuey-Yu; Shin, Jyh-Wei

    2015-01-01

    Background Trichomonas vaginalis is a protozoan parasite that occurs in the urogenital-vaginal tract and is the primary causative agent of trichomoniasis, a common sexually transmitted disease in humans. The aggregation of this protozoan tends to destroy epithelial cells and induce pathogenesis. Principal Findings This study cultured T. vaginalis and human cervical epithelial cells (Z172) under the same conditions in the experiments. Following co-culturing for ten hours, the protozoans became attached to Z172, such that the cells presented a round shape and underwent shrinkage. Time-lapse recording and flow cytometry on interacted Z172 revealed that 70% had been disrupted, 18% presented a necrosis-like morphology and 8% showed signs of apoptosis. Gene expression profiling revealed in the seven inflammatory Z172 genes as well as in T. vaginalis genes that code for adhesion proteins 65 and 65-1. Significance These results suggest that cytopathogenic effects progress while Z172 is in contact with T. vaginalis, and the resulting morphological changes can be categorized as disruption. PMID:25901354

  14. Controlled surface morphology and hydrophilicity of polycaprolactone toward human retinal pigment epithelium cells

    International Nuclear Information System (INIS)

    Shahmoradi, Saleheh; Yazdian, Fatemeh; Tabandeh, Fatemeh; Soheili, Zahra-Soheila; Hatamian Zarami, Ashraf Sadat; Navaei-Nigjeh, Mona

    2017-01-01

    Applying scaffolds as a bed to enhance cell proliferation and even differentiation is one of the treatment of retina diseases such as age-related macular degeneration (AMD) which deteriorating photoreceptors and finally happening blindness. In this study, aligned polycaprolactone (PCL) nanofibers were electrospun and at different conditions and their characteristics were measured by scanning electron microscope (SEM) and contact angle. Response surface methodology (RSM) was used to optimize the diameter of fabricated nanofibers. Two factors as solution concentration and voltage value were considered as independent variables and their effects on nanofibers' diameters were evaluated by central composite design and the optimum conditions were obtained as 0.12 g/mL and 20 kV, respectively. In order to decrease the hydrophobicity of PCL, the surface of the fabricated scaffolds was modified by alkaline hydrolysis method. Contact time of the scaffolds and alkaline solution and concentration of alkaline solution were optimized using Box Behnken design and (120 min and 5 M were the optimal, respectively). Contact angle measurement showed the high hydrophilicity of treated scaffolds (with contact angle 7.48°). Plasma surface treatment was applied to compare the effect of using two kinds of surface modification methods simultaneously on hydrolyzed scaffolds. The RPE cells grown on scaffolds were examined by immunocytochemistry (ICC), MTT and continuous inspection of cellular morphology. Interestingly, Human RPE cells revealed their characteristic morphology on hydrolyzed scaffold well. As a result, we introduced a culture substrate with low diameter (185.8 nm), high porosity (82%) and suitable hydrophilicity (with contact angle 7.48 degree) which can be promising for hRPE cell transplantation. - Highlights: • Dimethylformamide (DMF) has significant effect on reduction of fibers' diameter. • Having high hydrophilicity by alkaline hydrolysis • Suitable

  15. Controlled surface morphology and hydrophilicity of polycaprolactone toward human retinal pigment epithelium cells.

    Science.gov (United States)

    Shahmoradi, Saleheh; Yazdian, Fatemeh; Tabandeh, Fatemeh; Soheili, Zahra-Soheila; Hatamian Zarami, Ashraf Sadat; Navaei-Nigjeh, Mona

    2017-04-01

    Applying scaffolds as a bed to enhance cell proliferation and even differentiation is one of the treatment of retina diseases such as age-related macular degeneration (AMD) which deteriorating photoreceptors and finally happening blindness. In this study, aligned polycaprolactone (PCL) nanofibers were electrospun and at different conditions and their characteristics were measured by scanning electron microscope (SEM) and contact angle. Response surface methodology (RSM) was used to optimize the diameter of fabricated nanofibers. Two factors as solution concentration and voltage value were considered as independent variables and their effects on nanofibers' diameters were evaluated by central composite design and the optimum conditions were obtained as 0.12g/mL and 20kV, respectively. In order to decrease the hydrophobicity of PCL, the surface of the fabricated scaffolds was modified by alkaline hydrolysis method. Contact time of the scaffolds and alkaline solution and concentration of alkaline solution were optimized using Box Behnken design and (120min and 5M were the optimal, respectively). Contact angle measurement showed the high hydrophilicity of treated scaffolds (with contact angle 7.48°). Plasma surface treatment was applied to compare the effect of using two kinds of surface modification methods simultaneously on hydrolyzed scaffolds. The RPE cells grown on scaffolds were examined by immunocytochemistry (ICC), MTT and continuous inspection of cellular morphology. Interestingly, Human RPE cells revealed their characteristic morphology on hydrolyzed scaffold well. As a result, we introduced a culture substrate with low diameter (185.8nm), high porosity (82%) and suitable hydrophilicity (with contact angle 7.48 degree) which can be promising for hRPE cell transplantation. Copyright © 2016. Published by Elsevier B.V.

  16. Controlled surface morphology and hydrophilicity of polycaprolactone toward human retinal pigment epithelium cells

    Energy Technology Data Exchange (ETDEWEB)

    Shahmoradi, Saleheh; Yazdian, Fatemeh [Department of Life Science Engineering, Faculty of New sciences and Technologies, University of Tehran, Tehran (Iran, Islamic Republic of); Tabandeh, Fatemeh, E-mail: taban_f@nigeb.ac.ir [Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran (Iran, Islamic Republic of); Soheili, Zahra-Soheila [Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran (Iran, Islamic Republic of); Hatamian Zarami, Ashraf Sadat [Department of Life Science Engineering, Faculty of New sciences and Technologies, University of Tehran, Tehran (Iran, Islamic Republic of); Navaei-Nigjeh, Mona [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2017-04-01

    Applying scaffolds as a bed to enhance cell proliferation and even differentiation is one of the treatment of retina diseases such as age-related macular degeneration (AMD) which deteriorating photoreceptors and finally happening blindness. In this study, aligned polycaprolactone (PCL) nanofibers were electrospun and at different conditions and their characteristics were measured by scanning electron microscope (SEM) and contact angle. Response surface methodology (RSM) was used to optimize the diameter of fabricated nanofibers. Two factors as solution concentration and voltage value were considered as independent variables and their effects on nanofibers' diameters were evaluated by central composite design and the optimum conditions were obtained as 0.12 g/mL and 20 kV, respectively. In order to decrease the hydrophobicity of PCL, the surface of the fabricated scaffolds was modified by alkaline hydrolysis method. Contact time of the scaffolds and alkaline solution and concentration of alkaline solution were optimized using Box Behnken design and (120 min and 5 M were the optimal, respectively). Contact angle measurement showed the high hydrophilicity of treated scaffolds (with contact angle 7.48°). Plasma surface treatment was applied to compare the effect of using two kinds of surface modification methods simultaneously on hydrolyzed scaffolds. The RPE cells grown on scaffolds were examined by immunocytochemistry (ICC), MTT and continuous inspection of cellular morphology. Interestingly, Human RPE cells revealed their characteristic morphology on hydrolyzed scaffold well. As a result, we introduced a culture substrate with low diameter (185.8 nm), high porosity (82%) and suitable hydrophilicity (with contact angle 7.48 degree) which can be promising for hRPE cell transplantation. - Highlights: • Dimethylformamide (DMF) has significant effect on reduction of fibers' diameter. • Having high hydrophilicity by alkaline hydrolysis • Suitable

  17. Disease susceptibility of the human macula: differential gene transcription in the retinal pigmented epithelium/choroid.

    Science.gov (United States)

    Radeke, Monte J; Peterson, Katie E; Johnson, Lincoln V; Anderson, Don H

    2007-09-01

    The discoveries of gene variants associated with macular diseases have provided valuable insight into their molecular mechanisms, but they have not clarified why the macula is particularly vulnerable to degenerative disease. Its predisposition may be attributable to specialized structural features and/or functional properties of the underlying macular RPE/choroid. To examine the molecular basis for the macula's disease susceptibility, we compared the gene expression profile of the human RPE/choroid in the macula with the profile in the extramacular region using DNA microarrays. Seventy-five candidate genes with differences in macular:extramacular expression levels were identified by microarray analysis, of which 29 were selected for further analysis. Quantitative PCR confirmed that 21 showed statistically significant differences in expression. Five genes were expressed at higher levels in the macula. Two showed significant changes in the macular:extramacular expression ratio; another two exhibited changes in absolute expression level, as a function of age or AMD. Several of the differentially expressed genes have potential relevance to AMD pathobiology. One is an RPE cell growth factor (TFPI2), five are extracellular matrix components (DCN, MYOC, OGN, SMOC2, TFPI2), and six are related to inflammation (CCL19, CCL26, CXCL14, SLIT2) and/or angiogenesis (CXCL14, SLIT2, TFPI2, WFDC1). The identification of regional differences in gene expression in the RPE/choroid is a first step in clarifying the macula's propensity for degeneration. These findings lay the groundwork for further studies into the roles of the corresponding gene products in the normal, aged, and diseased macula.

  18. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses.

    Science.gov (United States)

    van Riel, Debby; den Bakker, Michael A; Leijten, Lonneke M E; Chutinimitkul, Salin; Munster, Vincent J; de Wit, Emmie; Rimmelzwaan, Guus F; Fouchier, Ron A M; Osterhaus, Albert D M E; Kuiken, Thijs

    2010-04-01

    Influenza viruses vary markedly in their efficiency of human-to-human transmission. This variation has been speculated to be determined in part by the tropism of influenza virus for the human upper respiratory tract. To study this tropism, we determined the pattern of virus attachment by virus histochemistry of three human and three avian influenza viruses in human nasal septum, conchae, nasopharynx, paranasal sinuses, and larynx. We found that the human influenza viruses-two seasonal influenza viruses and pandemic H1N1 virus-attached abundantly to ciliated epithelial cells and goblet cells throughout the upper respiratory tract. In contrast, the avian influenza viruses, including the highly pathogenic H5N1 virus, attached only rarely to epithelial cells or goblet cells. Both human and avian viruses attached occasionally to cells of the submucosal glands. The pattern of virus attachment was similar among the different sites of the human upper respiratory tract for each virus tested. We conclude that influenza viruses that are transmitted efficiently among humans attach abundantly to human upper respiratory tract, whereas inefficiently transmitted influenza viruses attach rarely. These results suggest that the ability of an influenza virus to attach to human upper respiratory tract is a critical factor for efficient transmission in the human population.

  19. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses

    NARCIS (Netherlands)

    D.A.J. van Riel (Debby); M.A. den Bakker (Michael); L.M.E. Leijten (Lonneke); S. Chutinimitkul (Salin); V.J. Munster (Vincent); E. de Wit (Emmie); G.F. Rimmelzwaan (Guus); R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2010-01-01

    textabstractInfluenza viruses vary markedly in their efficiency of human-to-human transmission. This variation has been speculated to be determined in part by the tropism of influenza virus for the human upper respiratory tract. To study this tropism, we determined the pattern of virus attachment by

  20. In Vitro Culture Conditions for Maintaining a Complex Population of Human Gastrointestinal Tract Microbiota

    Directory of Open Access Journals (Sweden)

    Bong-Soo Kim

    2011-01-01

    Full Text Available A stable intestinal microbiota is important in maintaining human physiology and health. Although there have been a number of studies using in vitro and in vivo approaches to determine the impact of diet and xenobiotics on intestinal microbiota, there is no consensus for the best in vitro culture conditions for growth of the human gastrointestinal microbiota. To investigate the dynamics and activities of intestinal microbiota, it is important for the culture conditions to support the growth of a wide range of intestinal bacteria and maintain a complex microbial community representative of the human gastrointestinal tract. Here, we compared the bacterial community in three culture media: brain heart infusion broth and high- and low-carbohydrate medium with different growth supplements. The bacterial community was analyzed using denaturing gradient gel electrophoresis (DGGE, pyrosequencing and real-time PCR. Based on the molecular analysis, this study indicated that the 3% fecal inoculum in low-concentration carbohydrate medium with 1% autoclaved fecal supernatant provided enhanced growth conditions to conduct in vitro studies representative of the human intestinal microbiota.

  1. Survival of Lactobacillus reuteri DSM 17938 and Lactobacillus rhamnosus GG in the Human Gastrointestinal Tract with Daily Consumption of a Low-Fat Probiotic Spread▿

    OpenAIRE

    Dommels, Yvonne E. M.; Kemperman, Robèr A.; Zebregs, Yvonne E. M. P.; Draaisma, René B.; Jol, Arne; Wolvers, Danielle A. W.; Vaughan, Elaine E.; Albers, Ruud

    2009-01-01

    Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. Therefore, probiotic strains should be able to survive passage through the human gastrointestinal tract. Human gastrointestinal tract survival of probiotics in a low-fat spread matrix has, however, never been tested. The objective of this randomized, double-blind, placebo-controlled human intervention study was to test the human gastrointestinal tract survival of Lactobacillus...

  2. Human papillomavirus and gastrointestinal cancer in Iranian population: A systematic review and meta-analysis.

    Science.gov (United States)

    Omrani-Navai, Versa; Alizadeh-Navaei, Reza; Yahyapour, Yousef; Hedayatizadeh-Omran, Akbar; Abediankenari, Saeid; Janbabaei, Ghasem; Toghani, Fatima

    2017-01-01

    Gastrointestinal (GI) malignancies are the most common cancers and account for nearly half of all cancer-related deaths in Iran. There was a strong association between human papillomavirus (HPV) infection and urogenital cancers, in particular the cervix. However, there is no clear causal relationship in all types of cancers, including gastrointestinal cancers. Therefore, the present study as a systematic review and meta-analysis was designed to evaluate the prevalence and relation of HPV in GI cancers. This systematic review and meta-analysis study assess the prevalence of human papillomavirus in GI cancers in Iran. Data were collected by searching electronic databases, including PubMed, Google Scholar, Scopus, SID and Iranmedex by English and Persian key words up to August 2016. Key words included: Human Papillomavirus, HPV, Cancer, Neoplasm, Carcinoma, Esophageal, colorectal, Gastrointestinal and Iran articles were entered in the EndNote software and duplicate papers were excluded. Data were extracted and analyzed by comprehensive meta-analysis software, Version 2 (CMA.V2) and random effects model. Finally, we included 17 studies in this meta-analysis. The prevalence of HPV in Iranian patients with GI cancers was 16.4% (CI95%: 10.4-24.9). Considering all HPV types, the odds ratio of GI cancers in positive patients was 3.03 (CI95%: 1.42-6.45) while in patients with HPV-16 was 3.62 (CI: 1.43-4.82). The results show a strong relationship between HPV infection especially high-risk HPV type 16 and GI cancers in Iranian population.

  3. PCR Expression Analysis Of the Estrogeninducible Gene Bcei in Gastrointestinal and Other Human Tumors

    Directory of Open Access Journals (Sweden)

    Iris Wundrack

    1994-01-01

    Full Text Available A polymerase chain reaction (PCR assay was developed to test for tumor cell specific expression of the BCEI gene. This new marker gene, reported at first for human breast cancer, was found specifically active in various gastrointestinal carcinomas by previously applying immunohistochemistry and RNA (Northern blot analysis. Presently, by using reverse transcription -PCR analysis, a series of primary tumor tissues and established tumor cell lines were testcd for BCEI transcription. This approach was compared to immunostaining achieved by an antibody directed against the BCEI gene’s product. The result demonstrate the superior sensitivity of PCR by indicating the gene’ s expression in cases where immunohistochemical testing remained negative.

  4. Zoonotic gastrointestinal parasite burden of local dogs in Zaria, Northern Nigeria: Implications for human health

    Directory of Open Access Journals (Sweden)

    Christopher I. Ogbaje

    2015-10-01

    Full Text Available Background: Zoonotic gastrointestinal parasites of dogs are of the global problem particularly in the developing countries. Dogs are the most common pet animals worldwide and have been reported to be hosts of many intestinal parasites of zoonotic importance globally. In Nigeria, gastrointestinal helminthes of dogs is currently endemic in 20 of the 36 states. Aim: In general, dogs are the closest animals to humans and for that reason we decided to carry out a survey study to check the incidence of these parasites in dogs and to ascertain the level of environmental contamination in the study area. Materials and Methods: Fecal samples were collected from dog patients presented to small animal clinic of Veterinary Teaching Hospital of Faculty of Veterinary Medicine, Ahmadu Bello University Zaria, dog’s fecal droppings from the streets, and residential Quarters of the University and gastrointestinal tracts (GIT of dogs from dogs slaughtering house at Basawa Barrack, Zaria. Three methods were used in the analysis of the samples; simple flotation, sedimentation, and GIT processing methods within 48 h of collection. Results: Out of 224 samples analyzed 76(33.9% were positive of at least one of the parasites. Of the 101 samples from streets and residential quarters of ABU, Zaria, Isospora spp. 12(11.9% recorded the highest prevalence rate followed by Taenia spp. 6(5.9%, then Toxocara canis, Ancylostoma caninum, and Dipylidium caninum were 5.0%, 4.0%, and 1.0%, respectively. Isospora spp. (19.0% recorded the highest prevalence rate for the 100 samples collected from small animal clinic. Other parasites encountered were T. canis (8.0%, A. caninum (8.0% and Taenia spp. (5.0%. Parasites observed from the 23 gastrointestinal contents from “dog slaughtered houses” were T. canis (17.3%, Isospora spp.(13.1% and A. caninum (4.3. Conclusion: The study revealed that zoonotic gastrointestinal parasites of dogs are endemic in Zaria and the general public in the

  5. Expression of Pluripotency and Oocyte-Related Genes in Single Putative Stem Cells from Human Adult Ovarian Surface Epithelium Cultured In Vitro in the Presence of Follicular Fluid

    Directory of Open Access Journals (Sweden)

    Irma Virant-Klun

    2013-01-01

    Full Text Available The aim of this study was to trigger the expression of genes related to oocytes in putative ovarian stem cells scraped from the ovarian surface epithelium of women with premature ovarian failure and cultured in vitro in the presence of follicular fluid, rich in substances for oocyte growth and maturation. Ovarian surface epithelium was scraped and cell cultures were set up by scrapings in five women with nonfunctional ovaries and with no naturally present mature follicles or oocytes. In the presence of donated follicular fluid putative stem cells grew and developed into primitive oocyte-like cells. A detailed single-cell gene expression profiling was performed to elucidate their genetic status in comparison to human embryonic stem cells, oocytes, and somatic fibroblasts. The ovarian cell cultures depleted/converted reproductive hormones from the culture medium. Estradiol alone or together with other substances may be involved in development of these primitive oocyte-like cells. The majority of primitive oocyte-like cells was mononuclear and expressed several genes related to pluripotency and oocytes, including genes related to meiosis, although they did not express some important oocyte-specific genes. Our work reveals the presence of putative stem cells in the ovarian surface epithelium of women with premature ovarian failure.

  6. Human in vivo and in vitro studies on gastrointestinal absorption of titanium dioxide nanoparticles.

    Science.gov (United States)

    Jones, Kate; Morton, Jackie; Smith, Ian; Jurkschat, Kerstin; Harding, Anne-Helen; Evans, Gareth

    2015-03-04

    The study was designed to conduct human in vivo and in vitro studies on the gastrointestinal absorption of nanoparticles, using titanium dioxide as a model compound, and to compare nanoparticle behaviour with that of larger particles. A supplier's characterisation data may not fully describe a particle formulation. Most particles tested agreed with their supplied characterisation when assessed by particle number but significant proportions of 'nanoparticle formulations' were particles >100nm when assessed by particle weight. Oral doses are measured by weight and it is therefore important that the weight characterisation is taken into consideration. The human volunteer studies demonstrated that very little titanium dioxide is absorbed gastrointestinally after an oral challenge. There was no demonstrable difference in absorption for any of the three particle sizes tested. All tested formulations were shown to agglomerate in simulated gastric fluid, particularly in the smaller particle formulations. Further agglomeration was observed when dispersing formulations in polymeric or elemental foods. Virtually no translocation of titanium dioxide particles across the cell layer was demonstrated. This study found no evidence that nanoparticulate titanium dioxide is more likely to be absorbed in the gut than micron-sized particles. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Comparison of five in vitro digestion models to in vivo experimental results: Lead bioaccessibility in the human gastrointestinal tract

    NARCIS (Netherlands)

    Wiele, T.R. van de; Oomen, A.G.; Wragg, J.; Cave, M.; Minekus, M.; Hack, A.; Cornelis, C.; Rompelberg, C.J.M.; Zwart, L.L. de; Klinck, B.; Wijnen, J. van; Verstraete, W.; Sips, A.J.A.M.

    2007-01-01

    This paper presents a multi-laboratory comparison study of in vitro models assessing bioaccessibility of soil-bound lead in the human gastrointestinal tract under simulated fasted and fed conditions. Oral bioavailability data from a previous human in vivo study on the same soil served as a reference

  8. Expression and Regulation of Drug Transporters and Metabolizing Enzymes in the Human Gastrointestinal Tract.

    Science.gov (United States)

    Drozdzik, M; Oswald, S

    2016-01-01

    Orally administered drugs must pass through the intestinal wall and then through the liver before reaching systemic circulation. During this process drugs are subjected to different processes that may determine the therapeutic value. The intestinal barrier with active drug metabolizing enzymes and drug transporters in enterocytes plays an important role in the determination of drug bioavailability. Accumulating information demonstrates variable distribution of drug metabolizing enzymes and transporters along the human gastrointestinal tract (GI), that creates specific barrier characteristics in different segments of the GI. In this review, expression of drug metabolizing enzymes and transporters in the healthy and diseased human GI as well as their regulatory aspects: genetic, miRNA, DNA methylation are outlined. The knowledge of unique interplay between drug metabolizing enzymes and transporters in specific segments of the GI tract allows more precise definition of drug release sites within the GI in order to assure more complete bioavailability and prediction of drug interactions.

  9. Development of a human corneal epithelium model utilizing a collagen vitrigel membrane and the changes of its barrier function induced by exposing eye irritant chemicals.

    Science.gov (United States)

    Takezawa, Toshiaki; Nishikawa, Kazunori; Wang, Pi-Chao

    2011-09-01

    The brief TEER (trans-epithelial electrical resistance) assay after exposing chemicals to corneal epithelium in vivo is known as a suitable method for evaluating corneal irritancy and permeability quantitatively and continuously. A collagen vitrigel membrane we previously developed is a thin (about 20 μm thick) and transparent membrane composed of high density collagen fibrils equivalent to connective tissues in vivo, e.g. corneal Bowman's membrane. To develop such a TEER assay system in vitro utilizing a human corneal epithelial model, HCE-T cells (a human corneal epithelial cell line) were cultured on the collagen vitrigel membrane substratum prepared in a Millicell chamber suitable for TEER measurement. Human corneal epithelium model possessing 5-6 cell layers sufficient for TEER assay was successfully reconstructed on the substratum in the Millicell chamber by culturing the cells in monolayer for 2 days and subsequently in air-liquid interface for 7 days. The exposure of chemicals to the model induced the time-dependent relative changes of TEER in response to the characteristic of each chemical within a few minutes. These results suggest that the TEER assay using the human corneal epithelial model is very useful for an ocular irritancy evaluation as an alternative to the Draize eye irritation test. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Modulation of the Gastrointestinal Microbiome with Nondigestible Fermentable Carbohydrates To Improve Human Health.

    Science.gov (United States)

    Deehan, Edward C; Duar, Rebbeca M; Armet, Anissa M; Perez-Muñoz, Maria Elisa; Jin, Mingliang; Walter, Jens

    2017-09-01

    There is a clear association between the gastrointestinal (GI) microbiome and the development of chronic noncommunicable diseases, providing a rationale for the development of strategies that target the GI microbiota to improve human health. In this article, we discuss the potential of supplementing the human diet with nondigestible fermentable carbohydrates (NDFCs) to modulate the composition, structure, diversity, and metabolic potential of the GI microbiome in an attempt to prevent or treat human disease. The current concepts by which NDFCs can be administered to humans, including prebiotics, fermentable dietary fibers, and microbiota-accessible carbohydrates, as well as the mechanisms by which these carbohydrates exert their health benefits, are discussed. Epidemiological research presents compelling evidence for the health effects of NDFCs, with clinical studies providing further support for some of these benefits. However, rigorously designed human intervention studies with well-established clinical markers and microbial endpoints are still essential to establish (i) the clinical efficiency of specific NDFCs, (ii) the causal role of the GI microbiota in these effects, (iii) the underlying mechanisms involved, and (iv) the degree by which inter-individual differences between GI microbiomes influence these effects. Such studies would provide the mechanistic understanding needed for a systematic application of NDFCs to improve human health via GI microbiota modulation while also allowing the personalization of these dietary strategies.

  11. Gastrointestinal motor inhibition by exogenous human, salmon, and eel calcitonin in conscious dogs.

    Science.gov (United States)

    Nakamura, H; Asano, T; Haruta, K; Takeda, K

    1995-01-01

    Effects of synthetic eel (E-), salmon (S-), and human (H-) calcitonin (CT) on gastrointestinal motility were studied in conscious beagle dogs, which had been implanted with strain gauge force transducers. Intramuscular administration of E-, S-, or H-CT interrupted gastric migrating motor complexes, digestive pattern, and gastric emptying. The order of potency was E-CT = S-CT > H-CT. Motor inhibition induced by CT occurred independently of plasma immunoreactive motilin levels or hypocalcemia. In addition, E-CT and S-CT induced vomiting without a retrograde giant contraction (RGC) during the postprandial state. Apomorphine or CuSO4 initiated RGC prior to vomiting. RGC induced by apomorphine was inhibited by pretreatment with E-CT as well as hexamethonium, atropine, or surgical vagotomy. E-CT showed no inhibitory effect on nicotine stimulated contraction of isolated guinea-pig ileum. These results suggest that peripherally administered CT inhibits canine gastrointestinal motility at the central nervous system level by lowering vagal activity.

  12. Antibodies against Escherichia coli O24 and O56 O-Specific Polysaccharides Recognize Epitopes in Human Glandular Epithelium and Nervous Tissue

    Science.gov (United States)

    Korzeniowska-Kowal, Agnieszka; Kochman, Agata; Gamian, Elżbieta; Lis-Nawara, Anna; Lipiński, Tomasz; Seweryn, Ewa; Ziółkowski, Piotr; Gamian, Andrzej

    2015-01-01

    Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, contains the O-polysaccharide, which is important to classify bacteria into different O-serological types within species. The O-polysaccharides of serotypes O24 and O56 of E. coli contain sialic acid in their structures, already established in our previous studies. Here, we report the isolation of specific antibodies with affinity chromatography using immobilized lipopolysaccharides. Next, we evaluated the reactivity of anti-O24 and anti-O56 antibody on human tissues histologically. The study was conducted under the assumption that the sialic acid based molecular identity of bacterial and tissue structures provides not only an understanding of the mimicry-based bacterial pathogenicity. Cross-reacting antibodies could be used to recognize specific human tissues depending on their histogenesis and differentiation, which might be useful for diagnostic purposes. The results indicate that various human tissues are recognized by anti-O24 and anti-O56 antibodies. Interestingly, only a single specific reactivity could be found in the anti-O56 antibody preparation. Several tissues studied were not reactive with either antibody, thus proving that the presence of cross-reactive antigens was tissue specific. In general, O56 antibody performed better than O24 in staining epithelial and nervous tissues. Positive staining was observed for both normal (ganglia) and tumor tissue (ganglioneuroma). Epithelial tissue showed positive staining, but an epitope recognized by O56 antibody should be considered as a marker of glandular epithelium. The reason is that malignant glandular tumor and its metastasis are stained, and also epithelium of renal tubules and glandular structures of the thyroid gland are stained. Stratified epithelium such as that of skin is definitely not stained. Therefore, the most relevant observation is that the epitope recognized by anti-O56 antibodies is a new marker

  13. Structural Injury after Lithium Treatment in Human and Rat Kidney involves Glycogen Synthase Kinase-3β Positive Epithelium

    DEFF Research Database (Denmark)

    Kjærsgaard, Gitte; Madsen, Kirsten; Marcussen, Niels

    2011-01-01

    Lithium is reabsorbed by distal nephron segments in sodium depleted states. It was hypothesized that lithium causes permanent injury to the developing kidney particularly in the sodium-retaining phase around weaning through entry into epithelial cells of the distal nephron and inhibition of glyco....... Lithium causes proliferation, structural injury and increases inactive pGSK-3β abundance in these segments. The data are compatible with epithelial entry of lithium and a causal role for GSK-3β in postnatal developing cortical collecting duct epithelium....

  14. Emulating Host-Microbiome Ecosystem of Human Gastrointestinal Tract in Vitro.

    Science.gov (United States)

    Park, Gun-Seok; Park, Min Hee; Shin, Woojung; Zhao, Connie; Sheikh, Sameer; Oh, So Jung; Kim, Hyun Jung

    2017-06-01

    The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human. However, controlling the multi-species microbial communities and their uncontrolled growth has remained a notable technical challenge. Furthermore, conventional two-dimensional (2D) or 3D culture systems do not recapitulate multicellular microarchitectures, mechanical dynamics, and tissue-specific functions. Here, we review recent advances and current pitfalls of in vitro and ex vivo models that display human GI functions. We also discuss how the disruptive technologies such as 3D organoids or a human organ-on-a-chip microphysiological system can contribute to better emulate host-gut microbiome crosstalks in health and disease. Finally, the medical and pharmaceutical significance of the gut microbiome-based personalized interventions is underlined as a future perspective.

  15. Substance P and substance K receptor binding sites in the human gastrointestinal tract: localization by autoradiography

    International Nuclear Information System (INIS)

    Gates, T.S.; Zimmerman, R.P.; Mantyh, C.R.; Vigna, S.R.; Maggio, J.E.; Welton, M.L.; Passaro, E.P. Jr.; Mantyh, P.W.

    1988-01-01

    Quantitative receptor autoradiography was used to localize and quantify the distribution of binding sites for 125 I-radiolabeled substance P (SP), substance K (SK) and neuromedin K (NK) in the human GI tract using histologically normal tissue obtained from uninvolved margins of resections for carcinoma. The distribution of SP and SK binding sites is different for each gastrointestinal (GI) segment examined. Specific SP binding sites are expressed by arterioles and venules, myenteric plexus, external circular muscle, external longitudinal muscle, muscularis mucosa, epithelial cells of the mucosa, and the germinal centers of lymph nodules. SK binding sites are distributed in a pattern distinct from SP binding sites and are localized to the external circular muscle, external longitudinal muscle, and the muscularis mucosa. Binding sites for NK were not detected in any part of the human GI tract. These results demonstrate that: (1) surgical specimens from the human GI tract can be effectively processed for quantitative receptor autoradiography; (2) of the three mammalian tachykinins tested, SP and SK, but not NK binding sites are expressed in detectable levels in the human GI tract; (3) whereas SK receptor binding sites are expressed almost exclusively by smooth muscle, SP binding sites are expressed by smooth muscle cells, arterioles, venules, epithelial cells of the mucosa and cells associated with lymph nodules; and (4) both SP and SK binding sites expressed by smooth muscle are more stable than SP binding sites expressed by blood vessels, lymph nodules, and mucosal cells

  16. Decreased VEGF-A and sustained PEDF expression in a human retinal pigment epithelium cell line cultured under hypothermia

    Directory of Open Access Journals (Sweden)

    Masayuki Takeyama

    2015-01-01

    Full Text Available BACKGROUND: Previous reports have described a decrease in retinal temperature and clinical improvement of wet age-related macular degeneration (AMD after vitrectomy. We hypothesized that the retinal temperature decrease after vitrectomy plays a part in the suppression of wet AMD development. To test this hypothesis, we evaluated the temperature dependence of the expression of vascular endothelial growth factor-A (VEGF-A and in vitro angiogen-esis in retinal pigment epithelium (RPE. RESULTS: We cultured ARPE-19 cells at 37, 35, 33 and 31°C and measured the expression of VEGF-A, VEGF-A splicing variants, and pigment epithelium-derived factor (PEDF. We performed an in vitro tube formation assay. The dehydrogenase activity was also evaluated at each temperature. Expression of VEGF-A significantly decreased with decreased temperature while PEDF expression did not. VEGF165 expression and in vitro angiogenesis also were temperature dependent. The dehydrogenase activity significantly decreased as the culture temperature decreased. CONCLUSIONS: RPE cultured under hypothermia that decreased cellular metabolism also had decreased VEGF-A and sustained PEDF expression, creating an anti-angiogenic environment. This mechanism may be associated with a beneficial effect after vitrectomy in patients with wet AMD.

  17. Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11

    International Nuclear Information System (INIS)

    Gregory-Bryson, Emmalena; Bartlett, Elizabeth; Kiupel, Matti; Hayes, Schantel; Yuzbasiyan-Gurkan, Vilma

    2010-01-01

    Gastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms in the gastrointestinal tract of humans and dogs. Little is known about the pathogenesis of these tumors. This study evaluated the role of c-KIT in canine GISTs; specifically, we investigated activating mutations in exons 8, 9, 11, 13, and 17 of c-KIT and exons 12, 14, and 18 of platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), all of which have been implicated in human GISTs. Seventeen canine GISTs all confirmed to be positive for KIT immunostaining were studied. Exons 8, 9, 11, 13 and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA, were amplified from DNA isolated from formalin-fixed paraffin-embedded samples. Of these seventeen cases, six amplicons of exon 11 of c-KIT showed aberrant bands on gel electrophoresis. Sequencing of these amplicons revealed heterozygous in-frame deletions in six cases. The mutations include two different but overlapping six base pair deletions. Exons 8, 9, 13, and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA had no abnormalities detected by electrophoresis and sequencing did not reveal any mutations, other than synonymous single nucleotide polymorphisms (SNPs) found in exon 11 of c-KIT and exons 12 and 14 of PDGFRA. The deletion mutations detected in canine GISTs are similar to those previously found in the juxtamembrane domain of c-KIT in canine cutaneous mast cell tumors in our laboratory as well as to those reported in human GISTs. Interestingly, none of the other c-KIT or PDGFRA exons showed any abnormalities in our cases. This finding underlines the critical importance of c-KIT in the pathophysiology of canine GISTs. The expression of KIT and the identification of these activating mutations in c-KIT implicate KIT in the pathogenesis of these tumors. Our results indicate that mutations in c-KIT may be of prognostic significance and that targeting KIT may be a rational approach to treatment of these malignant tumors. This study further

  18. Development of a serum-free co-culture of human intestinal epithelium cell-lines (Caco-2/HT29-5M21

    Directory of Open Access Journals (Sweden)

    Schneider Yves-Jacques

    2006-05-01

    Full Text Available Abstract Background The absorptive and goblet cells are the main cellular types encountered in the intestine epithelium. The cell lineage Caco-2 is a model commonly used to reproduce the features of the bowel epithelium. However, there is a strong debate regarding the value of Caco-2 cell culture to mimick in vivo situation. Indeed, some authors report in Caco-2 a low paracellular permeability and an ease of access of highly diffusible small molecules to the microvilli, due to an almost complete lack of mucus. The HT29-5M21 intestinal cell lineage is a mucin-secreting cellular population. A co-culture system carried out in a serum-free medium and comprising both Caco-2 and HT29-5M21 cells was developed. The systematic use of a co-culture system requires the characterization of the monolayer under a given experimental procedure. Results In this study, we investigated the activity and localization of the alkaline phosphatase and the expression of IAP and MUC5AC genes to determine a correlation between these markers and the cellular composition of a differentiated monolayer obtained from a mixture of Caco-2 and HT29-5M21 cells. We observed that the culture conditions used (serum-free medium did not change the phenotype of each cell type, and produced a reproducible model. The alkaline phosphatase expression characterizing Caco-2 cells was influenced by the presence of HT29-5M21 cells. Conclusion The culture formed by 75% Caco-2 and 25% HT29-5M21 produce a monolayer containing the two main cell types of human intestinal epithelium and characterized by a reduced permeability to macromolecules.

  19. Development of a serum-free co-culture of human intestinal epithelium cell-lines (Caco-2/HT29-5M21)

    Science.gov (United States)

    Nollevaux, Géraldine; Devillé, Christelle; El Moualij, Benaïssa; Zorzi, Willy; Deloyer, Patricia; Schneider, Yves-Jacques; Peulen, Olivier; Dandrifosse, Guy

    2006-01-01

    Background The absorptive and goblet cells are the main cellular types encountered in the intestine epithelium. The cell lineage Caco-2 is a model commonly used to reproduce the features of the bowel epithelium. However, there is a strong debate regarding the value of Caco-2 cell culture to mimick in vivo situation. Indeed, some authors report in Caco-2 a low paracellular permeability and an ease of access of highly diffusible small molecules to the microvilli, due to an almost complete lack of mucus. The HT29-5M21 intestinal cell lineage is a mucin-secreting cellular population. A co-culture system carried out in a serum-free medium and comprising both Caco-2 and HT29-5M21 cells was developed. The systematic use of a co-culture system requires the characterization of the monolayer under a given experimental procedure. Results In this study, we investigated the activity and localization of the alkaline phosphatase and the expression of IAP and MUC5AC genes to determine a correlation between these markers and the cellular composition of a differentiated monolayer obtained from a mixture of Caco-2 and HT29-5M21 cells. We observed that the culture conditions used (serum-free medium) did not change the phenotype of each cell type, and produced a reproducible model. The alkaline phosphatase expression characterizing Caco-2 cells was influenced by the presence of HT29-5M21 cells. Conclusion The culture formed by 75% Caco-2 and 25% HT29-5M21 produce a monolayer containing the two main cell types of human intestinal epithelium and characterized by a reduced permeability to macromolecules. PMID:16670004

  20. Regulation of EGF and Prostaglandin Expression during Neonatal Gastrointestinal Injury in a Non-Human Primate Explant Model

    Science.gov (United States)

    2017-05-05

    Neonatal Gastrointestinal Injury in a Non-Human Primate Explant Model presented at/published to Pediatric Academic Societies Meeting, San Francisco CA...Medical Center, San Antonio, Texas’ 2Department of Biology, Trinity University, San Antonio, Texas’ JDepartment of Pediatrics /Division of Neonatology

  1. Gastrointestinal parasites of canids, a latent risk to human health in Tunisia.

    Science.gov (United States)

    Oudni-M'rad, Myriam; Chaâbane-Banaoues, Raja; M'rad, Selim; Trifa, Fatma; Mezhoud, Habib; Babba, Hamouda

    2017-06-05

    Although data on the parasite environmental contamination are crucial to implement strategies for control and treatment, information about zoonotic helminths is very limited in Tunisia. Contamination of areas with canid faeces harboring infective parasite elements represents a relevant health-risk impact for humans. The aim of this study was to assess the environmental contamination with eggs and oocysts of gastrointestinal parasites of dogs and wild canids in Tunisia with special attention to those that can be transmitted to humans. One thousand two hundred and seventy faecal samples from stray dogs and 104 from wild canids (red foxes and golden jackals) were collected from different geographical regions throughout Tunisia. The helminth eggs and protozoan oocysts were concentrated by sucrose flotation and identified by microscopic examination. The most frequently observed parasites in dog samples were Toxocara spp. (27.2%), E. granulosus (25.8%), and Coccidia (13.1%). For wild canid faeces, the most commonly encountered parasites were Toxocara spp. (16.3%) followed by Capillaria spp. (9.6%). The parasite contamination of dog faeces varied significantly from one region to another in function of the climate. To our knowledge, the study highlights for the first time in Tunisia a serious environmental contamination by numerous parasitic stages infective to humans. Efforts should be made to increase the awareness of the contamination risk of such parasites in the environment and implement a targeted educational program.

  2. Taurine uptake by human retinal pigment epithelium: implications for the transport of small solutes between the choroid and the outer retina.

    Science.gov (United States)

    Hillenkamp, Jost; Hussain, Ali A; Jackson, Timothy L; Cunningham, Joanna R; Marshall, John

    2004-12-01

    To characterize the Michaelis-Menten kinetics of the taurine transporter (TT) in retinal pigment epithelium (RPE) freshly isolated from human donor eyes. To identify the rate limiting compartment in the pathway of taurine delivery from the choroidal blood supply to the outer retina composed by Bruch's-choroid (BC) and the RPE in the human older age group. In human donor samples (4 melanoma-affected eyes, and 14 control eyes; age range, 62-93 years), radiochemical techniques were used to determine the RPE taurine accumulation at various exogenous concentrations. The transport capability of human RPE was obtained from a kinetic analysis of the high-affinity carrier over a substrate concentration of 1 to 60 microM taurine. Uptake of taurine into human RPE at a taurine concentration of 1 microM was independent of donor age (P > 0.05) and averaged at 2.83 +/- 0.27 (SEM) pmol/10 minutes per 6-mm trephine. Taurine transport by human RPE was mediated by a high-affinity carrier of K(m) 50 microM and V(max) of 267 pmol/10 minutes per 5-mm disc. In human donor RPE, uptake of taurine remained viable in the age range 62 to 93 years. Taurine transport rates in the RPE were lower than across the isolated BC complex, and thus the data suggest that the former compartment houses the rate-limiting step in the delivery of taurine to the outer retina.

  3. A wireless capsule system with ASIC for monitoring the physiological signals of the human gastrointestinal tract.

    Science.gov (United States)

    Xu, Fei; Yan, Guozheng; Zhao, Kai; Lu, Li; Gao, Jinyang; Liu, Gang

    2014-12-01

    This paper presents the design of a wireless capsule system for monitoring the physiological signals of the human gastrointestinal (GI) tract. The primary components of the system include a wireless capsule, a portable data recorder, and a workstation. Temperature, pH, and pressure sensors; an RF transceiver; a controlling and processing application specific integrated circuit (ASIC); and batteries were applied in a wireless capsule. Decreasing capsule size, improving sensor precision, and reducing power needs were the primary challenges; these were resolved by employing micro sensors, optimized architecture, and an ASIC design that include power management, clock management, a programmable gain amplifier (PGA), an A/D converter (ADC), and a serial peripheral interface (SPI) communication unit. The ASIC has been fabricated in 0.18- μm CMOS technology with a die area of 5.0 mm × 5.0 mm. The wireless capsule integrating the ASIC controller measures Φ 11 mm × 26 mm. A data recorder and a workstation were developed, and 20 cases of human experiments were conducted in hospitals. Preprocessing in the workstation can significantly improve the quality of the data, and 76 original features were determined by mathematical statistics. Based on the 13 optimal features achieved in the evaluation of the features, the clustering algorithm can identify the patients who lack GI motility with a recognition rate reaching 83.3%.

  4. Reinstatement of "germinal epithelium" of the ovary

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    Nishida Naoyo

    2006-08-01

    Full Text Available Abstract Background The existing dogma that the former term ovarian "germinal epithelium" resulted from a mistaken belief that it could give rise to new germ cells is now strongly challenged. Discussion Two years ago, a research group of the University of Tennessee led by Antonin Bukovsky successfully demonstrated the oogenic process from the human ovarian covering epithelium now commonly called the ovarian surface epithelium. They showed the new oocyte with zona pellucida and granulosa cells, both originated from the surface epithelium arising from mesenchymal cells in the tunica albuginea, and stressed that the human ovary could form primary follicles throughout the reproductive period. This gives a big impact not only to the field of reproductive medicine, but also to the oncologic area. The surface epithelium is regarded as the major source of ovarian cancers, and most of the neoplasms exhibit the histology resembling müllerian epithelia. Since the differentiating capability of the surface epithelium has now expanded, the histologic range of the neoplasms in this category may extend to include both germ cell tumors and sex cord-stromal cell tumors. Summary Since the oogenic capability of ovarian surface cells has been proven, it is now believed that the oocytes can originate from them. The term "germinal epithelium", hence, might reasonably be reinstated.

  5. Estimation of the in vitro eye irritating and inflammatory potential of lipopolysaccharide (LPS) and dust by using reconstituted human corneal epithelium tissue cultures

    DEFF Research Database (Denmark)

    Cao, Yi; Arenholt-Bindslev, Dorthe; Kjærgaard, Søren K

    2015-01-01

    CONTEXT: Eye irritation is a common complaint in indoor environment, but the causes have still not been identified among the multiple exposures in house environments. To identify the potential environmental factors responsible for eye irritation and study the possible mechanisms, an in vitro model...... AND CONCLUSION: LPS and dust showed in vitro eye irritating and inflammatory potential, and cytokines/chemokines like IL-1β and IL-8 may be involved in the mechanisms of eye irritation. The HCE tissue culture may be used as an in vitro model to study environmental exposure induced eye irritation and inflammation....... for eye irritation is suggested. MATERIALS AND METHODS: In this study, reconstituted human corneal epithelium (HCE) tissue cultures were used to study the eye irritating and inflammatory potential of lipopolysaccharide (LPS) and dust. HCE tissue cultures were exposed to a range of concentrations of LPS...

  6. The spatiotemporal organization of cilia activity drives multiscale circular flows of mucus in reconstituted human bronchial epithelium

    Science.gov (United States)

    Loiseau, Etienne; Gras, Delphine; Chanez, Pascal; Viallat, Annie

    2017-11-01

    Chronic respiratory diseases affect hundreds of millions of people worldwide. The bronchial epithelium is the first barrier to protect the respiratory tract via an innate mechanism called mucociliary clearance. It consists in the active transport of a sticky fluid, the mucus, via a myriad of cilia at the epithelial surface of the airways. The mucus traps inhaled pathogens and the protective role of the mucociliary clearance relies on the ability of the cilia to self-organize and coordinate their beating to transport the mucus over the full bronchial tree till its elimination through swallowing or expectoration. Despite a rich corpus of clinical studies, chronic respiratory diseases remain poorly understood and quantitative biophysical studies are still missing. Here we will present the physical mechanisms underlying the mucociliary transport. We will show how the cilia self-organize during the ciliogenesis and how the coordination of their beating direction leads to the formation of fluid flow patterns at the macroscopic scale. Finally, we will discuss the role of long range hydrodynamics interactions in this intricate coupled system. ANR MUCOCIL project, Grant ANR-13-BSV5-0015 and European Union's Seventh Framework Programme (FP7/2007-2013) under REA Grant agreement n. PCOFUND-GA-2013-609102.

  7. Dioscorin protects tight junction protein expression in A549 human airway epithelium cells from dust mite damage.

    Science.gov (United States)

    Fu, Lin Shien; Ko, Ying Hsien; Lin, Kuo Wei; Hsu, Jeng Yuan; Chu, Jao Jia; Chi, Chin Shiang

    2009-12-01

    In addition to being an allergen, the trypsin activity of dust mite extract also destroys the tight junctions of bronchial epithelium. Such damage can lead to airway leakage, which increases airway exposure to allergens, irritants, and other pathogens. Dioscorin, the storage protein of yam, demonstrates anti-trypsin activity, as well as other potential anti-inflammatory effects. This study investigated the protective role of dioscorin for tight junctions. The immunofluorescence stains of zonula occludens (ZO-1), E-cadherin (EC) and desmoplakin (DP) proteins were compared. A cultured A549 cell line was used as a control and A549 cells were incubated with mite extract 100 mg/mL for 16 h, with or without dioscorin 100 mg/mL pretreatment for 8 h and with dioscorin 100 mg/mL alone for 16 h. Western blot was performed to detect changes in ZO-1, EC, and DP in the treated A549 cell lines. Loss of tight junction protein expression (ZO-1, EC, DP) was demonstrated after 16-h mite extract incubation. The defect could be restored if cells were pretreated with dioscorin for 8 h. In addition, dioscorin did not cause damage to the A549 cell lines in terms of cell survival or morphology. Western blot showed no change in the amount of tight junction protein under various conditions. Dioscorin is a potential protector of airway damage caused by mite extract.

  8. Tumor suppressor function of Syk in human MCF10A in vitro and normal mouse mammary epithelium in vivo.

    Directory of Open Access Journals (Sweden)

    You Me Sung

    2009-10-01

    Full Text Available The normal function of Syk in epithelium of the developing or adult breast is not known, however, Syk suppresses tumor growth, invasion, and metastasis in breast cancer cells. Here, we demonstrate that in the mouse mammary gland, loss of one Syk allele profoundly increases proliferation and ductal branching and invasion of epithelial cells through the mammary fat pad during puberty. Mammary carcinomas develop by one year. Syk also suppresses proliferation and invasion in vitro. siRNA or shRNA knockdown of Syk in MCF10A breast epithelial cells dramatically increased proliferation, anchorage independent growth, cellular motility, and invasion, with formation of functional, extracellular matrix-degrading invadopodia. Morphological and gene microarray analysis following Syk knockdown revealed a loss of luminal and differentiated epithelial features with epithelial to mesenchymal transition and a gain in invadopodial cell surface markers CD44, CD49F, and MMP14. These results support the role of Syk in limiting proliferation and invasion of epithelial cells during normal morphogenesis, and emphasize the critical role of Syk as a tumor suppressor for breast cancer. The question of breast cancer risk following systemic anti-Syk therapy is raised since only partial loss of Syk was sufficient to induce mammary carcinomas.

  9. A New High-Throughput Approach to Genotype Ancient Human Gastrointestinal Parasites.

    Science.gov (United States)

    Côté, Nathalie M L; Daligault, Julien; Pruvost, Mélanie; Bennett, E Andrew; Gorgé, Olivier; Guimaraes, Silvia; Capelli, Nicolas; Le Bailly, Matthieu; Geigl, Eva-Maria; Grange, Thierry

    2016-01-01

    Human gastrointestinal parasites are good indicators for hygienic conditions and health status of past and present individuals and communities. While microscopic analysis of eggs in sediments of archeological sites often allows their taxonomic identification, this method is rarely effective at the species level, and requires both the survival of intact eggs and their proper identification. Genotyping via PCR-based approaches has the potential to achieve a precise species-level taxonomic determination. However, so far it has mostly been applied to individual eggs isolated from archeological samples. To increase the throughput and taxonomic accuracy, as well as reduce costs of genotyping methods, we adapted a PCR-based approach coupled with next-generation sequencing to perform precise taxonomic identification of parasitic helminths directly from archeological sediments. Our study of twenty-five 100 to 7,200 year-old archeological samples proved this to be a powerful, reliable and efficient approach for species determination even in the absence of preserved eggs, either as a stand-alone method or as a complement to microscopic studies.

  10. Gastrointestinal transit in nonobese diabetic mouse: an animal model of human diabetes type 1.

    Science.gov (United States)

    El-Salhy, M

    2001-01-01

    Gastrointestinal transit (GI) in the nonobese diabetic (NOD) mouse, an animal model of human diabetes type 1, was examined in animals with short- (duration 1-5 days) and long-term (duration 28-35 days) diabetes. Blood glucose level, serum insulin concentration, and gut neuroendocrine peptide content were also measured. GI was significantly rapid in NOD mice with long-term diabetes (LTD), but was not correlated with blood glucose level, serum insulin concentration, or pancreatic insulin content. GI was correlated with duodenal secretin content, but not with the content of other neuroendocrine peptides in the different segments investigated. Whereas antral vasoactive intestinal peptide (VIP) content in NOD mice with LTD was significantly higher, colonic VIP was lower in NOD mice with short-term diabetes (STD). In the duodenum, whereas the concentration of secretin in NOD mice with both STD and LTD was lower, the gastrin content was higher. Duodenal somatostatin content in NOD mice with LTD was lower. In colon, the content of galanin in NOD mice with LTD was higher than in controls. The decreased content of secretin may be among the factors that cause rapid GI in NOD mice with LTD. Changes in the antral content of VIP, duodenal somatostatin, and colonic galanin in NOD mice with LTD may cause low intestinal secretion and, together with rapid GI, give rise to diarrhoea, which is a common symptom in diabetes.

  11. Effects of Dietary Yogurt on the Healthy Human Gastrointestinal (GI) Microbiome

    Science.gov (United States)

    Lisko, Daniel J.; Johnston, G. Patricia; Johnston, Carl G.

    2017-01-01

    The gastrointestinal (GI) tract performs key functions that regulate the relationship between the host and the microbiota. Research has shown numerous benefits of probiotic intake in the modulation of immune responses and human metabolic processes. However, unfavorable attention has been paid to temporal changes of the microbial composition and diversity of the GI tract. This study aimed to investigate the effects of yogurt consumption on the GI microbiome bacteria community composition, structure and diversity during and after a short-term period (42 days). We used a multi-approach combining classical fingerprinting techniques (T-RFLPs), Sanger analyses and Illumina MiSeq 16S rRNA gene amplicon sequencing to elucidate bacterial communities and Lactobacilli and Bifidobacteria populations within healthy adults that consume high doses of yogurt daily. Results indicated that overall GI microbial community and diversity was method-dependent, yet we found individual specific changes in bacterial composition and structure in healthy subjects that consumed high doses of yogurt throughout the study. PMID:28212267

  12. A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects.

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    Ece A Mutlu

    2014-02-01

    Full Text Available HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy.

  13. Effects of Genetically Modified Milk Containing Human Beta-Defensin-3 on Gastrointestinal Health of Mice.

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    Xin Chen

    Full Text Available This study was performed to investigate the effects of genetically modified (GM milk containing human beta-defensin-3 (HBD3 on mice by a 90-day feeding study. The examined parameters included the digestibility of GM milk, general physical examination, gastric emptying function, intestinal permeability, intestinal microflora composition of mice, and the possibility of horizontal gene transfer (HGT. The emphasis was placed on the effects on gastrointestinal (GI tract due to the fact that GI tract was the first site contacting with food and played crucial roles in metabolic reactions, nutrition absorption and immunity regulation in the host. However, the traditional methods for analyzing the potential toxicological risk of GM product pay little attention on GI health. In this study, the results showed GM milk was easy to be digested in simulated gastric fluid, and it did not have adverse effects on general and GI health compared to conventional milk. And there is little possibility of HGT. This study may enrich the safety assessment of GM product on GI health.

  14. Specific expression of human intelectin-1 in malignant pleural mesothelioma and gastrointestinal goblet cells.

    Directory of Open Access Journals (Sweden)

    Kota Washimi

    Full Text Available Malignant pleural mesothelioma (MPM is a fatal tumor. It is often hard to discriminate MPM from metastatic tumors of other types because currently, there are no reliable immunopathological markers for MPM. MPM is differentially diagnosed by some immunohistochemical tests on pathology specimens. In the present study, we investigated the expression of intelectin-1, a new mesothelioma marker, in normal tissues in the whole body and in many cancers, including MPM, by immunohistochemical analysis. We found that in normal tissues, human intelectin-1 was mainly secreted from gastrointestinal goblet cells along with mucus into the intestinal lumen, and it was also expressed, to a lesser extent, in mesothelial cells and urinary epithelial cells. Eighty-eight percent of epithelioid-type MPMs expressed intelectin-1, whereas sarcomatoid-type MPMs, biphasic MPMs, and poorly differentiated MPMs were rarely positive for intelectin-1. Intelectin-1 was not expressed in other cancers, except in mucus-producing adenocarcinoma. These results suggest that intelectin-1 is a better marker for epithelioid-type MPM than other mesothelioma markers because of its specificity and the simplicity of pathological assessment. Pleural intelectin-1 could be a useful diagnostic marker for MPM with applications in histopathological identification of MPM.

  15. Effects of Dietary Yogurt on the Healthy Human Gastrointestinal (GI Microbiome

    Directory of Open Access Journals (Sweden)

    Daniel J. Lisko

    2017-02-01

    Full Text Available The gastrointestinal (GI tract performs key functions that regulate the relationship between the host and the microbiota. Research has shown numerous benefits of probiotic intake in the modulation of immune responses and human metabolic processes. However, unfavorable attention has been paid to temporal changes of the microbial composition and diversity of the GI tract. This study aimed to investigate the effects of yogurt consumption on the GI microbiome bacteria community composition, structure and diversity during and after a short-term period (42 days. We used a multi-approach combining classical fingerprinting techniques (T-RFLPs, Sanger analyses and Illumina MiSeq 16S rRNA gene amplicon sequencing to elucidate bacterial communities and Lactobacilli and Bifidobacteria populations within healthy adults that consume high doses of yogurt daily. Results indicated that overall GI microbial community and diversity was method-dependent, yet we found individual specific changes in bacterial composition and structure in healthy subjects that consumed high doses of yogurt throughout the study.

  16. Age and gender affect the composition of fungal population of the human gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Francesco Strati

    2016-08-01

    Full Text Available The fungal component of the human gut microbiota has been neglected for long time due to the low relative abundance of fungi with respect to bacteria, and only recently few reports have explored its composition and dynamics in health or disease. The application of metagenomics methods to the full understanding of fungal communities is currently limited by the under representation of fungal DNA with respect to the bacterial one, as well as by the limited ability to discriminate passengers from colonizers. Here we investigated the gut mycobiota of a cohort of healthy subjects in order to reduce the gap of knowledge concerning fungal intestinal communities in the healthy status further screening for phenotypical traits that could reflect fungi adaptation to the host. We studied the fecal fungal populations of 111 healthy subjects by means of cultivation on fungal selective media and by amplicon-based ITS1 metagenomics analysis on a subset of 57 individuals. We then characterized the isolated fungi for their tolerance to gastrointestinal tract-like challenges and their susceptibility to antifungals. A total of 34 different fungal species were isolated showing several phenotypic characteristics associated with intestinal environment such as tolerance to body temperature (37°C, to acidic and oxidative stress and to bile salts exposure. We found a high frequency of azoles resistance in fungal isolates, with potential and significant clinical impact. Analyses of fungal communities revealed that the human gut mycobiota differs in function of individuals’ life stage in a gender-related fashion. The combination of metagenomics and fungal cultivation allowed an in-depth understanding of the fungal intestinal community structure associated to the healthy status and the commensalism-related traits of isolated fungi. We further discussed comparatively the results of sequencing and cultivation to critically evaluate the application of metagenomics

  17. Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture

    Science.gov (United States)

    Malik, Deepika; Tarek, Mohamed; Caceres del Carpio, Javier; Ramirez, Claudio; Boyer, David; Kenney, M Cristina; Kuppermann, Baruch D

    2014-01-01

    Purpose To compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture. Methods Human retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death. Results Cell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p<0.0001), but not at lower concentrations. However, no changes were seen in cell viability in ranibizumab-treated cells at all concentrations including 10×. Mitochondrial membrane potential was slightly decreased in 10× ranibizumab-treated cells (89.61%, p=0.0006) and 2× and 10× aflibercept-treated cells (88.76%, 81.46%; p<0.01, respectively). A larger reduction in mitochondrial membrane potential was seen at 1×, 2× and 10× concentrations of bevacizumab (86.53%, 74.38%, 66.67%; p<0.01) and ziv-aflibercept (73.50%, 64.83% and 49.65% p<0.01) suggestive of early apoptosis at lower doses, including the clinical doses. Conclusions At clinical doses, neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity or cell death. However, bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically relevant doses. PMID:24836865

  18. Efeito protetor da lactoferrina humana no trato gastrintestinal Efecto protector de la lactoferrina humana en el sistema gastrointestinal Protective effect of human lactoferrin in the gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Valterlinda Alves de O. Queiroz

    2013-03-01

    ón de morbilidades gastrointestinales. FUENTES DE DATOS: Revisión no sistemática de la literatura utilizando como estrategia de búsqueda investigación bibliográfica en bases de datos, que incluyeron SciELO, Lilacs y MedLine entre 1990 y 2011. Los descriptores utilizados fueron: lactoferrina, leche materna/humana, gastrointestinal e inmunidad, en los idiomas portugués e inglés. SÍNTESIS DE LOS DATOS: La lactoferrina es la segunda proteína predominante en la leche humana, con concentraciones más elevadas en el calostro (5,0 a 6,7mg/mL respecto a la leche madura (0,2 a 2,6mg/mL. En contraste, la leche de vaca contiene tenores inferiores, 0,83mg/mL en el calostro y 0,09mg/mL en la leche madura. La lactoferrina desempeña diversas funciones fisiológicas en la protección del sistema gastrointestinal. La actividad antimicrobiana está relacionada a la capacidad de secuestrar hierro de los fluidos biológicos y/o de desestructurar la membrana de microorganismos. La lactoferrina posee además la capacidad de estimular la proliferación celular. La acción antiinflamatoria desempeñada por la lactoferrina está asociada a la capacidad de penetrar en el núcleo del leucocito y bloquear la transcripción del nuclear factor Kappa B. Frente a la importancia de la lactoferrina en la prevención de enfermedades infecciosas en niños amamantados al pecho, la industria viene, por medio de ingeniería genética, desarrollando tecnologías para expresar esta proteína recombinante humana en plantas y animales en el intento de adecuar la composición de las fórmulas infantiles a aquella de la leche humana. CONCLUSIONES: La lactoferrina humana es un péptido con potencial para prevenir morbilidades, especialmente las gastrointestinales. Evidencias científicas de los efectos protectores de la lactoferrina humana fortalecen todavía más la recomendación para la práctica de la lactancia materna.OBJECTIVE: To describe mechanisms of action of human lactoferrin to protect

  19. Comparison of four decontamination treatments on porcine renal decellularized extracellular matrix structure, composition, and support of human renal cortical tubular epithelium cells.

    Science.gov (United States)

    Poornejad, Nafiseh; Nielsen, Jeffery J; Morris, Ryan J; Gassman, Jason R; Reynolds, Paul R; Roeder, Beverly L; Cook, Alonzo D

    2016-03-01

    Engineering whole organs from porcine decellularized extracellular matrix and human cells may lead to a plentiful source of implantable organs. Decontaminating the porcine decellularized extracellular matrix scaffolds is an essential step prior to introducing human cells. However, decontamination of whole porcine kidneys is a major challenge because the decontamination agent or irradiation needs to diffuse deep into the structure to eliminate all microbial contamination while minimizing damage to the structure and composition of the decellularized extracellular matrix. In this study, we compared four decontamination treatments that could be applicable to whole porcine kidneys: 70% ethanol, 0.2% peracetic acid in 1 M NaCl, 0.2% peracetic acid in 4% ethanol, and gamma (γ)-irradiation. Porcine kidneys were decellularized by perfusion of 0.5% (w/v) aqueous solution of sodium dodecyl sulfate and the four decontamination treatments were optimized using segments (n = 60) of renal tissue to ensure a consistent comparison. Although all four methods were successful in decontamination, γ-irradiation was very damaging to collagen fibers and glycosaminoglycans, leading to less proliferation of human renal cortical tubular epithelium cells within the porcine decellularized extracellular matrix. The effectiveness of the other three optimized solution treatments were then all confirmed using whole decellularized porcine kidneys (n = 3). An aqueous solution of 0.2% peracetic acid in 1 M NaCl was determined to be the best method for decontamination of porcine decellularized extracellular matrix. © The Author(s) 2015.

  20. Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter-Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth.

    Directory of Open Access Journals (Sweden)

    Shian-Ying Sung

    Full Text Available Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor-promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter-driven herpes simplex virus thymidine kinase gene (Ad-522E-TK was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers.

  1. ABCB1 (P-glycoprotein) reduces bacterial attachment to human gastrointestinal LS174T epithelial cells.

    Science.gov (United States)

    Crowe, Andrew; Bebawy, Mary

    2012-08-15

    The aim of this project was to show elevated P-glycoprotein (P-gp) expression decreasing bacterial association with LS174T human gastrointestinal cells, and that this effect could be reversed upon blocking functional P-gp efflux. Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Lactobacillus acidophilus and numerous strains of Escherichia coli, from commensal to enteropathogenic and enterohaemorrhagic strains (O157:H7) were fluorescently labelled and incubated on LS174T cultures either with or without P-gp amplification using rifampicin. PSC-833 was used as a potent functional P-gp blocking agent. Staphylococcus and Pseudomonas displayed the greatest association with the LS174T cells. Surprisingly, lactobacilli retained more fluorescence than enteropathogenic-E. coli in this system. Irrespective of attachment differences between the bacterial species, the increase in P-gp protein expression decreased bacterial fluorescence by 25-30%. This included the GFP-labelled E. coli, and enterohaemorrhagic E. coli (O157:H7). Blocking P-gp function through the co-administration of PSC-833 increased the amount of bacteria associated with P-gp expressing LS174T cells back to control levels. As most bacteria were affected to the same degree, irrespective of pathogenicity, it is unlikely that P-gp has a direct influence on adhesion of bacteria, and instead P-gp may be playing an indirect role by secreting a bank of endogenous factors or changing the local environment to one less suited to bacterial growth in general. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  2. Impact of lactic Acid bacteria on dendritic cells from allergic patients in an experimental model of intestinal epithelium.

    Science.gov (United States)

    Ratajczak, Céline; Duez, Catherine; Grangette, Corinne; Pochard, Pierre; Tonnel, André-Bernard; Pestel, Joël

    2007-01-01

    Lactic acid bacteria (LAB) are Gram positive nonpathogenic commensal organisms present in human gastrointestinal tract. In vivo, LAB are separated from antigen-presenting cells such as dendritic cells (DC) by the intestinal epithelial barrier. In this study, the impact of one LAB strain (Lactobacillus casei ATCC393) on human monocyte-derived DC from allergic and healthy donors was assessed by using a polarized epithelium model. Confocal and flow cytometer analyses showed that immature DC efficiently captured FITC-labelled L. casei through the epithelial layer. After interaction with L. casei, DC acquired a partial maturation status (i.e., CD86 and CD54 increase) and increased their interleukin (IL)-10 and IL-12 production. Interestingly, after activation by L. casei in the presence of experimental epithelium, DC from allergic patients instructed autologous naïve CD4(+) T cells to produce more interferon-gamma than without the epithelium. Thus by modulating human DC reactivity, LAB and intestinal epithelium might modify T cell immune response and regulate the development of allergic reaction.

  3. Impact of Lactic Acid Bacteria on Dendritic Cells from Allergic Patients in an Experimental Model of Intestinal Epithelium

    Directory of Open Access Journals (Sweden)

    Céline Ratajczak

    2007-01-01

    Full Text Available Lactic acid bacteria (LAB are Gram positive nonpathogenic commensal organisms present in human gastrointestinal tract. In vivo, LAB are separated from antigen-presenting cells such as dendritic cells (DC by the intestinal epithelial barrier. In this study, the impact of one LAB strain (Lactobacillus casei ATCC393 on human monocyte-derived DC from allergic and healthy donors was assessed by using a polarized epithelium model. Confocal and flow cytometer analyses showed that immature DC efficiently captured FITC-labelled L. casei through the epithelial layer. After interaction with L. casei, DC acquired a partial maturation status (i.e., CD86 and CD54 increase and increased their interleukin (IL-10 and IL-12 production. Interestingly, after activation by L. casei in the presence of experimental epithelium, DC from allergic patients instructed autologous naïve CD4+ T cells to produce more interferon-γ than without the epithelium. Thus by modulating human DC reactivity, LAB and intestinal epithelium might modify T cell immune response and regulate the development of allergic reaction.

  4. Pigment epithelium derived factor inhibits the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro.

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    Yanmei Sun

    Full Text Available Angiogenesis is a prerequisite for the formation and development of endometriosis. Pigment epithelium derived factor (PEDF is a natural inhibitor of angiogenesis. We previously demonstrated a reduction of PEDF in the peritoneal fluid, serum and endometriotic lesions from women with endometriosis compared with women without endometriosis. Here, we aim to investigate the inhibitory effect of PEDF on human endometriotic cells in vivo and in vitro. We found that PEDF markedly inhibited the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro by up-regulating PEDF expression and down-regulating vascular endothelial growth factor (VEGF expression. Moreover, apoptotic index was significantly increased in endometriotic lesions in vivo and endometriotic stromal cells in vitro when treated with PEDF. In mice treated with PEDF, decreased microvessel density labeled by Von Willebrand factor but not by α-Smooth Muscle Actin was observed in endometriotic lesions. And it showed no increase in PEDF expression of the ovary and uterus tissues. These findings suggest that PEDF gene therapy may be a new treatment for endometriosis.

  5. Time of day and eating behaviors are associated with the composition and function of the human gastrointestinal microbiota.

    Science.gov (United States)

    Kaczmarek, Jennifer L; Musaad, Salma Ma; Holscher, Hannah D

    2017-11-01

    Background: Preclinical research has shown that the gastrointestinal microbiota exhibits circadian rhythms and that the timing of food consumption can affect the composition and function of gut microbes. However, there is a dearth of knowledge on these relations in humans. Objective: We aimed to determine whether human gastrointestinal microbes and bacterial metabolites were associated with time of day or behavioral factors, including eating frequency, percentage of energy consumed early in the day, and overnight-fast duration. Design: We analyzed 77 fecal samples collected from 28 healthy men and women. Fecal DNA was extracted and sequenced to determine the relative abundances of bacterial operational taxonomic units (OTUs). Gas chromatography-mass spectroscopy was used to assess short-chain fatty acid concentrations. Eating frequency, percentage of energy consumed before 1400, and overnight-fast duration were determined from dietary records. Data were analyzed by linear mixed models or generalized linear mixed models, which controlled for fiber intake, sex, age, body mass index, and repeated sampling within each participant. Each OTU and metabolite were tested as the outcome in a separate model. Results: Acetate, propionate, and butyrate concentrations decreased throughout the day ( P = 0.006, 0.04, and 0.002, respectively). Thirty-five percent of bacterial OTUs were associated with time. In addition, relations were observed between gut microbes and eating behaviors, including eating frequency, early energy consumption, and overnight-fast duration. Conclusions: These results indicate that the human gastrointestinal microbiota composition and function vary throughout the day, which may be related to the circadian biology of the human body, the microbial community itself, or human eating behaviors. Behavioral factors, including timing of eating and overnight-fast duration, were also predictive of bacterial abundances. Longitudinal intervention studies are needed to

  6. Interaction of PHM, PHI and 24-glutamine PHI with human VIP receptors from colonic epithelium: comparison with rat intestinal receptors

    International Nuclear Information System (INIS)

    Laburthe, M.; Couvineau, A.; Rouyer-Fessard, C.; Moroder, L.

    1985-01-01

    PHM, the human counterpart of porcine Peptide Histidine Isoleucine amide (PHI), is shown to be a VIP agonist with low potency on human VIP receptors located in colonic epithelial cell membranes. Its potency is identical to that of PHI but by 3 orders of magnitude lower than that of VIP itself in inhibiting 125 I-VIP binding and in stimulating adenylate cyclase activity. This contrasts markedly with the behavior of PHI on rat VIP receptors located in intestinal epithelial cell membranes where PHI is a potent agonist with a potency that is 1/5 that of VIP. In another connection, the authors show that 24-glutamine PHI has the same affinity as 24-glutamic acid PHI (the natural peptide) for rat or human VIP receptors. These results indicate that while PHI may exert some physiological function through its interaction with VIP receptors in rodents, its human counterpart PHM is a very poor agonist of VIP in human. Furthermore, they show that the drastic change in position 24 of PHI (neutral versus acid residue) does not affect the activity of PHI, at least on VIP receptors. 21 references, 1 figure

  7. Gene expression profiles of human dendritic cells interacting with Aspergillus fumigatus in a bilayer model of the alveolar epithelium/endothelium interface.

    Directory of Open Access Journals (Sweden)

    Charles Oliver Morton

    Full Text Available The initial stages of the interaction between the host and Aspergillus fumigatus at the alveolar surface of the human lung are critical in the establishment of aspergillosis. Using an in vitro bilayer model of the alveolus, including both the epithelium (human lung adenocarcinoma epithelial cell line, A549 and endothelium (human pulmonary artery epithelial cells, HPAEC on transwell membranes, it was possible to closely replicate the in vivo conditions. Two distinct sub-groups of dendritic cells (DC, monocyte-derived DC (moDC and myeloid DC (mDC, were included in the model to examine immune responses to fungal infection at the alveolar surface. RNA in high quantity and quality was extracted from the cell layers on the transwell membrane to allow gene expression analysis using tailored custom-made microarrays, containing probes for 117 immune-relevant genes. This microarray data indicated minimal induction of immune gene expression in A549 alveolar epithelial cells in response to germ tubes of A. fumigatus. In contrast, the addition of DC to the system greatly increased the number of differentially expressed immune genes. moDC exhibited increased expression of genes including CLEC7A, CD209 and CCL18 in the absence of A. fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups exhibited up-regulation of genes identified in previous studies as being associated with the exposure of DC to A. fumigatus and exhibiting chemotactic properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model closely approximated the human alveolus allowing for an analysis of the host pathogen interface that complements existing animal models of IA.

  8. The migration and loss of human primordial germ stem cells from the hind gut epithelium towards the gonadal ridge

    DEFF Research Database (Denmark)

    Mamsen, Linn Salto; Brøchner, Christian Beltoft; Byskov, Anne Grete

    2012-01-01

    system in this process. Sixteen human specimens, 5-14 wpc obtained from legal abortions were included. On serial paraffin sections, PGCs were detected immunohistochemically by expression of OCT4 and c-Kit, nerve fibers by ß-III-tubulin and stem cell factor (SCF) as a possible chemoattractive cue for PGC...

  9. Human testis-expressed sequence 101 is limitedly distributed in germinal epithelium of testis and disappears in seminoma

    Directory of Open Access Journals (Sweden)

    Cong-Cong Shen

    2014-01-01

    Full Text Available BACKGROUND: Testis-expressed sequence 101 (TEX101 was found to be highly expressed in testis and involved in acrosome reaction in previous studies. Recently, the metastasis suppressor function of TEX101 in cancer was disclosed, but the comprehensive investigation of its expression has rarely been reported. In this study, the expression features of TEX101 in normal human organs and seminoma were systematically analyzed. RESULTS: Immunohistochemistry demonstrated intense staining of TEX101 in human testis tissues; however, its expression in 27 other types of normal human organs, including the ovary, was negligible. Higher expression of TEX101 was observed in the spermatocytes and spermatids of the testis, but relatively lower staining was detected in spermatogonia. Western blotting showed a single TEX101 band of 38 kDa in human testis, but it did not correspond to the predicted molecular weight of its mature form at 21 KDa. Furthermore, we examined seminoma tissues by immunohistochemistry and found that none of the 36 samples expressed TEX101. CONCLUSIONS: Our data confirmed TEX101 to be a testis protein that could be related to the maturation process of male germ cells. The lack of TEX101 in seminoma indicated its potential role in tumor progression. This characteristic expression of TEX101 could provide a valuable reference for understanding its biological functions.

  10. Presence of human papillomavirus in semen of healthy men is firmly associated with HPV infections of the penile epithelium

    NARCIS (Netherlands)

    Luttmer, Roosmarijn; Dijkstra, Maaike G.; Snijders, Peter J. F.; Jordanova, Ekaterina S.; King, Audrey J.; Pronk, Divera T. M.; Foresta, Carlo; Garolla, Andrea; Hompes, Peter G. A.; Berkhof, Johannes; Bleeker, Maaike C. G.; Doorbar, John; Heideman, Daniëlle A. M.; Meijer, Chris J. L. M.

    2015-01-01

    To study the source of human papillomavirus (HPV) in semen. Observational study (CCMO-NL3248800010). Academic hospital-based laboratory. Healthy male volunteers (n = 213). One penile scrape and three semen samples were obtained per participant for HPV-DNA testing by both GP5+/6+ polymerase chain

  11. Effect of dark-colored maple syrup on cell proliferation of human gastrointestinal cancer cell

    Science.gov (United States)

    Yamamoto, Tetsushi; Sato, Kanta; Kubota, Yuika; Mitamura, Kuniko; Taga, Atsushi

    2017-01-01

    Maple syrup is a natural sweetener that is commonly consumed worldwide. While maple syrup mainly comprises sucrose, it also contains phytochemicals that present various biological effects. Maple syrup is made by boiling down sap, and its color and composition vary in accordance with the sap collection season. Typically, seasonal progression is associated with darker syrup color, and antioxidant activity is proportional to the increasingly dark color. The authors previously reported that maple syrup demonstrated inhibitory effects on colorectal cancer cell growth and invasion, which correlated with darker maple syrup color. In the present study, they examined the effects of two different grades of maple syrup on gastrointestinal cancer cell proliferation, to investigate whether the dark-color maple syrup was suitable as a phytomedicine for gastrointestinal cancer treatment. Administration of dark-color maple syrup significantly inhibited gastrointestinal cancer cell growth as compared to non-treated cancer cells. Moreover, administration of dark-color maple syrup clearly inhibited protein kinase B (AKT) phosphorylation and did not impact mitogen-associated protein kinase phosphorylation. These data suggested that dark-color maple syrup may inhibit cell proliferation through suppression of AKT activation and, thus, may be suitable as a phytomedicine for gastrointestinal cancer treatment. PMID:28685052

  12. Stability of milk fat globule membrane proteins toward human enzymatic gastrointestinal digestion.

    Science.gov (United States)

    Le, T T; Van de Wiele, T; Do, T N H; Debyser, G; Struijs, K; Devreese, B; Dewettinck, K; Van Camp, J

    2012-05-01

    The milk fat globule membrane (MFGM) fraction refers to the thin film of polar lipids and membrane proteins that surrounds fat globules in milk. It is its unique biochemical composition that renders MFGM with some beneficial biological activities, such as anti-adhesive effects toward pathogens. However, a prerequisite for the putative bioactivity of MFGM is its stability during gastrointestinal digestion. We, therefore, subjected MFGM material, isolated from raw milk, to an in vitro enzymatic gastrointestinal digestion. Sodium dodecyl sulfate PAGE, in combination with 2 staining methods, Coomassie Blue and periodic acid Schiff staining, was used to evaluate polypeptide patterns of the digest, whereas mass spectrometry was used to confirm the presence of specific MFGM proteins. Generally, it was observed that glycoproteins showed higher resistance to endogenous proteases compared with non-glycosylated proteins. Mucin 1 displayed the highest resistance to digestion and a considerable part of this protein was still detected at its original molecular weight after gastric and small intestine digestion. Cluster of differentiation 36 was also quite resistant to pepsin. A significant part of periodic acid Schiff 6/7 survived the gastric digestion, provided that the lipid moiety was not removed from the MFGM material. Overall, MFGM glycoproteins are generally more resistant to gastrointestinal digestion than serum milk proteins and the presence of lipids, besides glycosylation, may protect MFGM glycoproteins from gastrointestinal digestion. This gastrointestinal stability makes MFGM glycoproteins amenable to further studies in which their putative health-promoting effects can be explored. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. A new 3D reconstituted human corneal epithelium model as an alternative method for the eye irritation test.

    Science.gov (United States)

    Jung, Kyoung-Mi; Lee, Su-Hyon; Ryu, Yang-Hwan; Jang, Won-Hee; Jung, Haeng-Sun; Han, Ju-Hee; Seok, Seung-Hyeok; Park, Jae-Hak; Son, Youngsook; Park, Young-Ho; Lim, Kyung-Min

    2011-02-01

    Many efforts are being made to develop new alternative in vitro test methods for the eye irritation test. Here we report a new reconstructed human corneal epithelial model (MCTT HCE model) prepared from primary-cultured human limbal epithelial cells as a new alternative in vitro eye irritation test method. In histological and immunohistochemical observation, MCTT HCE model displayed a morphology and biomarker expressions similar to intact human cornea. Moreover, the barrier function was well preserved as measured by high transepithelial electrical resistance, effective time-50 for Triton X-100, and corneal thickness. To employ the model as a new alternative method for eye irritation test, protocol refinement was performed and optimum assay condition was determined including treatment time, treatment volume, post-incubation time and rinsing method. Using the refined protocol, 25 reference chemicals with known eye irritation potentials were tested. With the viability cut-off value at 50%, chemicals were classified to irritant or non-irritant. When compared with GHS classification, the MCTT HCE model showed the accuracy of 88%, sensitivity of 100% and specificity of 77%. These results suggest that the MCTT HCE model might be useful as a new alternative eye irritation test method. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Response of exfoliated human buccal epithelium cells to combined gamma radiation, microwaves, and magnetic field exposure estimated by changes in chromatin condensation and cell membrane permeability

    Directory of Open Access Journals (Sweden)

    K. А. Kuznetsov

    2016-11-01

    Full Text Available Modulation of the biological effects produced by ionizing radiation (IR using microwave and magnetic fields has important theoretical and practical applications. Response of human buccal epithelium cells to different physical agents (single and combined exposure to 0.5–5 Gy γ-radiation (60Co; microwaves with the frequency of 36.64 GHz and power densities of 0.1 and 1 W/m2, and static magnetic field with the intensity of 25 mT has been investigated. The stress response of the cells was evaluated by counting heterochromatin granules quantity (HGQ in the cell nuclei stained with orcein. Membrane permeability was assessed by the percentage of cells stained with indigocarmine (cells with damaged membrane. The increase of heterochromatin granules quantity (HGQ, i.e. chromatin condensation was detected at the doses of 2 Gy and higher. Changes in the cell membrane permeability to indigocarmine expressed the threshold effect. Membrane permeability reached the threshold at the doses of 2–3 Gy for the cells of different donors and did not change with the increase of the dose of γ-radiation. Cells obtained from different donors revealed some individual peculiarities in their reaction to γ-radiation. The static magnetic field and microwaves applied before or after γ-radiation decreased its impact, as revealed by means of HGQ assessment.

  15. Effects of cyclic-nucleotide derivatives on the growth of human colonic carcinoma xenografts and on cell production in the rat colonic crypt epithelium.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1981-08-01

    Previous studies have shown that various amine hormones are able to influence the growth rate of human colorectal carcinomas propagated as xenografts in immune-deprived mice, and it is now well known that the effects of many amine and other hormones are mediated by cyclic nucleotides, acting as second messengers within cells. In the present study the influence of various derivatives of cyclic adenosine monophosphate and cyclic guanosine monophosphate on the growth of two different lines of colorectal cancer growing in immune-deprived mice, and on the cell production rate in the colonic crypt epithelium of the rat, was assessed. Growth of each tumour line, as well as crypt-cell production, was suppressed by treatment wit N6O2' dibutyryl and N6 monobutyryl derivatives of cyclic adenosine monophosphate. Dibutyryl cyclic guanosine monophosphate, on the other hand, was found to promote the growth of Tumour HXK4 and to promote crypt cell production, but to have no significant effect on Tumour HXM2.

  16. Estimation of the in vitro eye irritating and inflammatory potential of lipopolysaccharide (LPS) and dust by using reconstituted human corneal epithelium tissue cultures.

    Science.gov (United States)

    Cao, Yi; Bindslev, Dorthe A; Kjærgaard, Søren K

    2015-01-01

    Eye irritation is a common complaint in indoor environment, but the causes have still not been identified among the multiple exposures in house environments. To identify the potential environmental factors responsible for eye irritation and study the possible mechanisms, an in vitro model for eye irritation is suggested. In this study, reconstituted human corneal epithelium (HCE) tissue cultures were used to study the eye irritating and inflammatory potential of lipopolysaccharide (LPS) and dust. HCE tissue cultures were exposed to a range of concentrations of LPS for 6 h and dust for 24 h, respectively. After exposure, viability and secretion of interleukins (IL) IL-1β, IL-8, and tumor necrosis factor (TNFα) were examined. Histology was used to indicate the morphological changes after dust exposure. Both LPS and dust affected HCE viability. There was an increased level of IL-8 after LPS exposure, while the concentrations of IL-1β and TNFα remained unaffected. Dust exposure resulted in an elevation of both IL-1β and IL-8, but not TNFα. Histology study showed increased vacuolization and reduced thickness after 24 h exposure to 5 mg/mL dust. LPS and dust showed in vitro eye irritating and inflammatory potential, and cytokines/chemokines like IL-1β and IL-8 may be involved in the mechanisms of eye irritation. The HCE tissue culture may be used as an in vitro model to study environmental exposure induced eye irritation and inflammation.

  17. Neuropilin-2 mediated β-catenin signaling and survival in human gastro-intestinal cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Shaija Samuel

    Full Text Available NRP-2 is a high-affinity kinase-deficient receptor for ligands belonging to the class 3 semaphorin and vascular endothelial growth factor families. NRP-2 has been detected on the surface of several types of human cancer cells, but its expression and function in gastrointestinal (GI cancer cells remains to be determined. We sought to determine the function of NRP-2 in mediating downstream signals regulating the growth and survival of human gastrointestinal cancer cells. In human gastric cancer specimens, NRP-2 expression was detected in tumor tissues but not in adjacent normal mucosa. In CNDT 2.5 cells, shRNA mediated knockdown NRP-2 expression led to decreased migration and invasion in vitro (p<0.01. Focused gene-array analysis demonstrated that loss of NRP-2 reduced the expression of a critical metastasis mediator gene, S100A4. Steady-state levels and function of β-catenin, a known regulator of S100A4, were also decreased in the shNRP-2 clones. Furthermore, knockdown of NRP-2 sensitized CNDT 2.5 cells in vitro to 5FU toxicity. This effect was associated with activation of caspases 3 and 7, cleavage of PARP, and downregulation of Bcl-2. In vivo growth of CNDT 2.5 cells in the livers of nude mice was significantly decreased in the shNRP-2 group (p<0.05. Intraperitoneal administration of NRP-2 siRNA-DOPC decreased the tumor burden in mice (p = 0.01. Collectively, our results demonstrate that tumor cell-derived NRP-2 mediates critical survival signaling in gastrointestinal cancer cells.

  18. Role of yqiC in the pathogenicity of Salmonella and innate immune responses of human intestinal epithelium

    Directory of Open Access Journals (Sweden)

    Ke-Chuan Wang

    2016-10-01

    Full Text Available The yqiC gene of Salmonella enterica serovar Typhimurium (S. Typhimurium regulates bacterial growth at different temperatures and mice survival after infection. However, the role of yqiC in bacterial colonization and host immunity remains unknown. We infected human LS174T, Caco-2, HeLa, and THP-1 cells with S. Typhimurium wild-type SL1344, its yqiC mutant, and its complemented strain. Bacterial colonization and internalization in the four cell lines significantly reduced on yqiC depletion. Postinfection production of interleukin-8 and human β-defensin-3 in LS174T cells significantly reduced because of yqiC deleted in S. Typhimurium. The phenotype of yqiC mutant exhibited few and short flagella, fimbriae on the cell surface, enhanced biofilm formation, upregulated type-1 fimbriae expression, and reduced bacterial motility. Type-1 fimbriae, flagella, SPI-1, and SPI-2 gene expression was quantified using real-time PCR. The data show that deletion of yqiC upregulated fimA and fimZ expression and downregulated flhD, fliZ, invA, and sseB expression. Furthermore, thin-layer chromatography and high-performance liquid chromatography revealed the absence of menaquinone in the yqiC mutant, thus validating the importance of yqiC in the bacterial electron transport chain. Therefore, YqiC can negatively regulate FimZ for type-1 fimbriae expression and manipulate the functions of its downstream virulence factors including flagella, SPI-1, and SPI-2 effectors.

  19. RT-PCR detection of Candida albicans ALS gene expression in the reconstituted human epithelium (RHE) model of oral candidiasis and in model biofilms.

    Science.gov (United States)

    Green, Clayton B; Cheng, Georgina; Chandra, Jyotsna; Mukherjee, Pranab; Ghannoum, Mahmoud A; Hoyer, Lois L

    2004-02-01

    An RT-PCR assay was developed to analyse expression patterns of genes in the Candida albicans ALS (agglutinin-like sequence) family. Inoculation of a reconstituted human buccal epithelium (RHE) model of mucocutaneous candidiasis with strain SC5314 showed destruction of the epithelial layer by C. albicans and also formation of an upper fungal layer that had characteristics similar to a biofilm. RT-PCR analysis of total RNA samples extracted from C. albicans-inoculated buccal RHE showed that ALS1, ALS2, ALS3, ALS4, ALS5 and ALS9 were consistently detected over time as destruction of the RHE progressed. Detection of transcripts from ALS7, and particularly from ALS6, was more sporadic, but not associated with a strictly temporal pattern. The expression pattern of ALS genes in C. albicans cultures used to inoculate the RHE was similar to that observed in the RHE model, suggesting that contact of C. albicans with buccal RHE does little to alter ALS gene expression. RT-PCR analysis of RNA samples extracted from model denture and catheter biofilms showed similar gene expression patterns to the buccal RHE specimens. Results from the RT-PCR analysis of biofilm RNA specimens were consistent between various C. albicans strains during biofilm development and were comparable to gene expression patterns in planktonic cells. The RT-PCR assay described here will be useful for analysis of human clinical specimens and samples from other disease models. The method will provide further insight into the role of ALS genes and their encoded proteins in the diverse interactions between C. albicans and its host.

  20. Profile of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium determined through serial analysis of gene expression (SAGE)

    Science.gov (United States)

    Sharon, Dror; Blackshaw, Seth; Cepko, Constance L.; Dryja, Thaddeus P.

    2002-01-01

    We used the serial analysis of gene expression (SAGE) technique to catalogue and measure the relative levels of expression of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium (RPE) from one or both of two humans, aged 88 and 44 years. The cone photoreceptor contribution to all transcription in the retina was found to be similar in the macula versus the retinal periphery, whereas the rod contribution was greater in the periphery versus the macula. Genes encoding structural proteins for axons were found to be expressed at higher levels in the macula versus the retinal periphery, probably reflecting the large proportion of ganglion cells in the central retina. In comparison with the younger eye, the peripheral retina of the older eye had a substantially higher proportion of mRNAs from genes encoding proteins involved in iron metabolism or protection against oxidative damage and a substantially lower proportion of mRNAs from genes encoding proteins involved in rod phototransduction. These differences may reflect the difference in age between the two donors or merely interindividual variation. The RPE library had numerous previously unencountered tags, suggesting that this cell type has a large, idiosyncratic repertoire of expressed genes. Comparison of these libraries with 100 reported nonocular SAGE libraries revealed 89 retina-specific or enriched genes expressed at substantial levels, of which 14 are known to cause a retinal disease and 53 are RPE-specific genes. We expect that these libraries will serve as a resource for understanding the relative expression levels of genes in the retina and the RPE and for identifying additional disease genes. PMID:11756676

  1. Cadherins in the retinal pigment epithelium (RPE revisited: P-cadherin is the highly dominant cadherin expressed in human and mouse RPE in vivo.

    Directory of Open Access Journals (Sweden)

    Xue Yang

    Full Text Available The retinal pigment epithelium (RPE supports the health and function of retinal photoreceptors and is essential for normal vision. RPE cells are post-mitotic, terminally differentiated, and polarized epithelial cells. In pathological conditions, however, they lose their epithelial integrity, become dysfunctional, even dedifferentiate, and ultimately die. The integrity of epithelial cells is maintained, in part, by adherens junctions, which are composed of cadherin homodimers and p120-, β-, and α-catenins linking to actin filaments. While E-cadherin is the major cadherin for forming the epithelial phenotype in most epithelial cell types, it has been reported that cadherin expression in RPE cells is different from other epithelial cells based on results with cultured RPE cells. In this study, we revisited the expression of cadherins in the RPE to clarify their relative contribution by measuring the absolute quantity of cDNAs produced from mRNAs of three classical cadherins (E-, N-, and P-cadherins in the RPE in vivo. We found that P-cadherin (CDH3 is highly dominant in both mouse and human RPE in situ. The degree of dominance of P-cadherin is surprisingly large, with mouse Cdh3 and human CDH3 accounting for 82-85% and 92-93% of the total of the three cadherin mRNAs, respectively. We confirmed the expression of P-cadherin protein at the cell-cell border of mouse RPE in situ by immunofluorescence. Furthermore, we found that oxidative stress induces dissociation of P-cadherin and β-catenin from the cell membrane and subsequent translocation of β-catenin into the nucleus, resulting in activation of the canonical Wnt/β-catenin pathway. This is the first report of absolute comparison of the expression of three cadherins in the RPE, and the results suggest that the physiological role of P-cadherin in the RPE needs to be reevaluated.

  2. Modulation of ingestive behavior and gastrointestinal motility by ghrelin in diabetic animals and humans.

    Science.gov (United States)

    Chen, Chih-Yen; Fujimiya, Mineko; Laviano, Alessandro; Chang, Full-Young; Lin, Han-Chieh; Lee, Shou-Dong

    2010-05-01

    Acyl ghrelin, a 28-amino acid peptide hormone, is the endogenous cognate ligand for the growth hormone secretagogue receptor. Ghrelin is involved in stimulating growth hormone release, eliciting feeding behavior, inducing adiposity and stimulating gastrointestinal motility. Ghrelin is unique for its post-translational modification of O-n-octanoylation at serine 3 through ghrelin O-acyltransferase, and is the only peripheral signal to enhance food intake. Plasma ghrelin levels manifest "biphasic changes" in diabetes mellitus (DM). In the early stage of DM, the stomach significantly increases the secretion of ghrelin into the plasma, and elevated plasma ghrelin levels are correlated with diabetic hyperphagic feeding and accelerated gastrointestinal motility. In the late stage of DM, plasma ghrelin levels may be lower, which might be linked with anorexia/muscle wasting, delayed gastrointestinal transit, and even gastroparesis. Therefore, the unique ghrelin system may be the most important player compared to the other hindgut hormones participating in the "entero-insular axis". Further studies using either knockdown or knockout of ghrelin gene products and ghrelin O-acyltransferase may unravel the pathogenesis of DM, and show benefits in combating this disease and metabolic syndrome. Copyright 2010 Elsevier. Published by Elsevier B.V. All rights reserved.

  3. Modulation of Ingestive Behavior and Gastrointestinal Motility by Ghrelin in Diabetic Animals and Humans

    Directory of Open Access Journals (Sweden)

    Chih-Yen Chen

    2010-05-01

    Full Text Available Acyl ghrelin, a 28-amino acid peptide hormone, is the endogenous cognate ligand for the growth hormone secretagogue receptor. Ghrelin is involved in stimulating growth hormone release, eliciting feeding behavior, inducing adiposity and stimulating gastrointestinal motility. Ghrelin is unique for its post-translational modification of O-n-octanoylation at serine 3 through ghrelin O-acyltransferase, and is the only peripheral signal to enhance food intake. Plasma ghrelin levels manifest “biphasic changes” in diabetes mellitus (DM. In the early stage of DM, the stomach significantly increases the secretion of ghrelin into the plasma, and elevated plasma ghrelin levels are correlated with diabetic hyperphagic feeding and accelerated gastrointestinal motility. In the late stage of DM, plasma ghrelin levels may be lower, which might be linked with anorexia/muscle wasting, delayed gastrointestinal transit, and even gastroparesis. Therefore, the unique ghrelin system may be the most important player compared to the other hindgut hormones participating in the “entero-insular axis”. Further studies using either knockdown or knockout of ghrelin gene products and ghrelin O-acyltransferase may unravel the pathogenesis of DM, and show benefits in combating this disease and metabolic syndrome.

  4. Distribution of obestatin and ghrelin in human tissues: immunoreactive cells in the gastrointestinal tract, pancreas, and mammary glands

    DEFF Research Database (Denmark)

    Grönberg, Malin; Tsolakis, Apostolos V; Magnusson, Linda

    2008-01-01

    Obestatin and ghrelin are two peptides derived from the same prohormone. It is well established that ghrelin is produced by endocrine cells in the gastric mucosa. However, the distribution of human obestatin immunoreactive cells is not thoroughly characterized. A polyclonal antibody...... that specifically recognizes human obestatin was produced. Using this antibody and a commercial antibody vs ghrelin, the distribution of obestatin and ghrelin immunoreactive cells was determined in a panel of human tissues using immunohistochemistry. The two peptides were detected in the mucosa...... of the gastrointestinal tract, from cardia to ileum, and in the pancreatic islets. Interestingly, epithelial cells in the ducts of mammary glands showed distinct immunoreactivity for both ghrelin and obestatin. By double immunofluorescence microscopy, it was shown that all detected cells were immunoreactive for both...

  5. CON4EI: SkinEthic™ Human Corneal Epithelium Eye Irritation Test (SkinEthic™ HCE EIT) for hazard identification and labelling of eye irritating chemicals.

    Science.gov (United States)

    Van Rompay, A R; Alépée, N; Nardelli, L; Hollanders, K; Leblanc, V; Drzewiecka, A; Gruszka, K; Guest, R; Kandarova, H; Willoughby, J A; Verstraelen, S; Adriaens, E

    2018-06-01

    Assessment of ocular irritancy is an international regulatory requirement and a necessary step in the safety evaluation of industrial and consumer products. Although a number of in vitro ocular irritation assays exist, none are capable of fully categorizing chemicals as a stand-alone assay. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was developed with the goal of assessing the reliability of eight in vitro/alternative test methods as well as establishing an optimal tiered-testing strategy. One of the in vitro assays selected was the validated SkinEthic™ Human Corneal Epithelium Eye Irritation Test method (SkinEthic™ HCE EIT). The SkinEthic™ HCE EIT has already demonstrated its capacity to correctly identify chemicals (both substances and mixtures) not requiring classification and labelling for eye irritation or serious eye damage (No Category). The goal of this study was to evaluate the performance of the SkinEthic™ HCE EIT test method in terms of the important in vivo drivers of classification. For the performance with respect to the drivers all in vivo Cat 1 and No Cat chemicals were 100% correctly identified. For Cat 2 chemicals the liquids and the solids had a sensitivity of 100% and 85.7%, respectively. For the SkinEthic™ HCE EIT test method, 100% concordance in predictions (No Cat versus No prediction can be made) between the two participating laboratories was obtained. The accuracy of the SkinEthic™ HCE EIT was 97.5% with 100% sensitivity and 96.9% specificity. The SkinEthic™ HCE EIT confirms its excellent results of the validation studies. Copyright © 2017. Published by Elsevier Ltd.

  6. First Insights into the Diverse Human Archaeome: Specific Detection of Archaea in the Gastrointestinal Tract, Lung, and Nose and on Skin

    Directory of Open Access Journals (Sweden)

    Kaisa Koskinen

    2017-11-01

    Full Text Available Human-associated archaea remain understudied in the field of microbiome research, although in particular methanogenic archaea were found to be regular commensals of the human gut, where they represent keystone species in metabolic processes. Knowledge on the abundance and diversity of human-associated archaea is extremely limited, and little is known about their function(s, their overall role in human health, or their association with parts of the human body other than the gastrointestinal tract and oral cavity. Currently, methodological issues impede the full assessment of the human archaeome, as bacteria-targeting protocols are unsuitable for characterization of the full spectrum of Archaea. The goal of this study was to establish conservative protocols based on specifically archaea-targeting, PCR-based methods to retrieve first insights into the archaeomes of the human gastrointestinal tract, lung, nose, and skin. Detection of Archaea was highly dependent on primer selection and the sequence processing pipeline used. Our results enabled us to retrieve a novel picture of the human archaeome, as we found for the first time Methanobacterium and Woesearchaeota (DPANN superphylum to be associated with the human gastrointestinal tract and the human lung, respectively. Similar to bacteria, human-associated archaeal communities were found to group biogeographically, forming (i the thaumarchaeal skin landscape, (ii the (methanoeuryarchaeal gastrointestinal tract, (iii a mixed skin-gastrointestinal tract landscape for the nose, and (iv a woesearchaeal lung landscape. On the basis of the protocols we used, we were able to detect unexpectedly high diversity of archaea associated with different body parts.

  7. R5 HIV-1 envelope attracts dendritic cells to cross the human intestinal epithelium and sample luminal virions via engagement of the CCR5.

    Science.gov (United States)

    Cavarelli, Mariangela; Foglieni, Chiara; Rescigno, Maria; Scarlatti, Gabriella

    2013-05-01

    The gastrointestinal tract is a principal route of entry and site of persistence of human immunodeficiency virus type 1 (HIV-1). The intestinal mucosa, being rich of cells that are the main target of the virus, represents a primary site of viral replication and CD4(+) T-cell depletion. Here, we show both in vitro and ex vivo that HIV-1 of R5 but not X4 phenotype is capable of selectively triggering dendritic cells (DCs) to migrate within 30 min between intestinal epithelial cells to sample virions and transfer infection to target cells. The engagement of the chemokine receptor 5 on DCs and the viral envelope, regardless of the genetic subtype, drive DC migration. Viruses penetrating through transient opening of the tight junctions likely create a paracellular gradient to attract DCs. The formation of junctions with epithelial cells may initiate a haptotactic process of DCs and at the same time favour cell-to-cell viral transmission. Our findings indicate that HIV-1 translocation across the intestinal mucosa occurs through the selective engagement of DCs by R5 viruses, and may guide the design of new prevention strategies. Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  8. A dimensionless ordered pull-through model of the mammalian lens epithelium evidences scaling across species and explains the age-dependent changes in cell density in the human lens

    Science.gov (United States)

    Wu, Jun Jie; Wu, Weiju; Tholozan, Frederique M.; Saunter, Christopher D.; Girkin, John M.; Quinlan, Roy A.

    2015-01-01

    We present a mathematical (ordered pull-through; OPT) model of the cell-density profile for the mammalian lens epithelium together with new experimental data. The model is based upon dimensionless parameters, an important criterion for inter-species comparisons where lens sizes can vary greatly (e.g. bovine (approx. 18 mm); mouse (approx. 2 mm)) and confirms that mammalian lenses scale with size. The validated model includes two parameters: β/α, which is the ratio of the proliferation rate in the peripheral and in the central region of the lens; and γGZ, a dimensionless pull-through parameter that accounts for the cell transition and exit from the epithelium into the lens body. Best-fit values were determined for mouse, rat, rabbit, bovine and human lens epithelia. The OPT model accounts for the peak in cell density at the periphery of the lens epithelium, a region where cell proliferation is concentrated and reaches a maximum coincident with the germinative zone. The β/α ratio correlates with the measured FGF-2 gradient, a morphogen critical to lens cell survival, proliferation and differentiation. As proliferation declines with age, the OPT model predicted age-dependent changes in cell-density profiles, which we observed in mouse and human lenses. PMID:26236824

  9. A Sensitive and Rapid Method to Determine the Adhesion Capacity of Probiotics and Pathogenic Microorganisms to Human Gastrointestinal Mucins

    Directory of Open Access Journals (Sweden)

    Bélinda Ringot-Destrez

    2018-05-01

    Full Text Available Mucus is the habitat for the microorganisms, bacteria and yeast that form the commensal flora. Mucins, the main macromolecules of mucus, and more specifically, the glycans that cover them, play essential roles in microbial gastrointestinal colonization. Probiotics and pathogens must also colonize mucus to have lasting positive or deleterious effects. The question of which mucin-harboured glycan motifs favour the adhesion of specific microorganisms remains very poorly studied. In the current study, a simple test based on the detection of fluorescent-labeled microorganisms raised against microgram amounts of mucins spotted on nitrocellulose was developed. The adhesion of various probiotic, commensal and pathogenic microorganisms was evaluated on a panel of human purified gastrointestinal mucins and compared with that of commercially available pig gastric mucins (PGM and of mucins secreted by the colonic cancer cell line HT29-MTX. The latter two proved to be very poor indicators of adhesion capacity on intestinal mucins. Our results show that the nature of the sialylated cores of O-glycans, determined by MALDI MS-MS analysis, potentially enables sialic acid residues to modulate the adhesion of microorganisms either positively or negatively. Other identified factors affecting the adhesion propensity were O-glycan core types and the presence of blood group motifs. This test should help to select probiotics with enhanced adhesion capabilities as well as deciphering the role of specific mucin glycotopes on microbial adhesion.

  10. Stem Cells in Repair of Gastrointestinal Epithelia

    NARCIS (Netherlands)

    Andersson-Rolf, Amanda; Zilbauer, Matthias; Koo, Bon-Kyoung; Clevers, Hans

    Among the endodermal tissues of adult mammals, the gastrointestinal (GI) epithelium exhibits the highest turnover rate. As the ingested food moves along the GI tract, gastric acid, digestive enzymes, and gut resident microbes aid digestion as well as nutrient and mineral absorption. Due to the harsh

  11. Comparison of the gastrointestinal absorption and bioavailability of fenofibrate and fenofibric acid in humans.

    Science.gov (United States)

    Zhu, Tong; Ansquer, Jean-Claude; Kelly, Maureen T; Sleep, Darryl J; Pradhan, Rajendra S

    2010-08-01

    This study compared the gastrointestinal (GI) absorption characteristics and absolute bioavailability of fenofibric acid and fenofibrate (which is converted to fenofibric acid in vivo) in healthy volunteers. Treatments were delivered to the proximal small bowel, distal small bowel, and colon using a site-specific delivery system (Enterion capsule) and to the stomach by oral administration of equimolar doses. Serial blood samples were collected for 120 hours postdose and assayed for plasma fenofibric acid concentrations. The absolute bioavailability of each treatment was determined relative to 50 mg of fenofibric acid administered intravenously. Plasma exposure to fenofibric acid following fenofibric acid administration was approximately 1.5 times higher than that following fenofibrate administration for delivery to the proximal and distal small bowel and following oral administration, and it was approximately 5 times higher following colon delivery. The absolute bioavailability in the stomach, proximal small bowel, distal small bowel, and colon was approximately 81%, 88%, 84%, and 78%, respectively, for fenofibric acid and 69%, 73%, 66%, and 22%, respectively, for fenofibrate (P < .0001 and P = .033 for fenofibric acid vs fenofibrate in the colon and distal small bowel, respectively). In conclusion, fenofibric acid is well absorbed throughout the GI tract and has greater bioavailability than fenofibrate in all GI regions.

  12. Tumor-Initiating Label-Retaining Cancer Cells in Human Gastrointestinal Cancers Undergo Asymmetric Cell Division

    Science.gov (United States)

    Xin, Hong-Wu; Hari, Danielle M.; Mullinax, John E.; Ambe, Chenwi M.; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J.; Wiegand, Gordon W.; Garfield, Susan H.; Thorgeirsson, Snorri S.; Avital, Itzhak

    2012-01-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

  13. Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis

    NARCIS (Netherlands)

    Gori, Andrea; Tincati, Camilla; Rizzardini, Giuliano; Torti, Carlo; Quirino, Tiziana; Haarman, Monique; Ben Amor, Kaouther; van Schaik, Jacqueline; Vriesema, Aldwin; Knol, Jan; Marchetti, Giulia; Welling, Gjalt; Clerici, Mario

    Our results show that impairment of the gastrointestinal tracts in human immunodeficiency virus (HIV)-positive patients is present in the early phases of HIV disease. This impairment is associated with alterations in gut microbiota and intestinal inflammatory parameters. These findings support the

  14. Human-associated fecal qPCR measurements and predicted risk of gastrointestinal illness in recreational waters contaminated with raw sewage

    Science.gov (United States)

    We used quantitative microbial risk assessment (QMRA) to estimate the risk of gastrointestinal (GI) illness associated with swimming in recreational waters containing different concentrations of human-associated fecal qPCR markers from raw sewage– HF183 and HumM2. The volume/volu...

  15. Human-Associated Fecal Quantitative Polymerase Chain ReactionMeasurements and Simulated Risk of Gastrointestinal Illness in Recreational Waters Contaminated with Raw Sewage

    Science.gov (United States)

    We used quantitative microbial risk assessment (QMRA) to estimate the risk of gastrointestinal (GI) illness associated with swimming in recreational waters containing different concentrations of human-associated fecal qPCR markers from raw sewage– HF183 and HumM2. The volume/volu...

  16. Gastrointestinal absorption of plutonium and uranium in fed and fasted adult baboons and mice: application to humans

    International Nuclear Information System (INIS)

    Bhattacharyya, M.H.; Larsen, R.P.; Oldham, R.D.; Cohen, N.; Ralston, L.G.; Moretti, E.S.; Ayres, L.

    1989-01-01

    Gastrointestinal (GI) absorption values of plutonium and uranium were determined in fed and fasted adult baboons and mice. For both baboons and mice, the GI absorptions of plutonium and uranium were 10 to 20 times higher in 24 h fasted animals than in fed ones. For plutonium, GI absorption values in baboons were almost identical to those in mice for both fed and fasted conditions, and values for fed animals agreed with estimates for humans. For uranium, GI absorption values in fed and fasted baboons were 6 to 7 times higher than those in mice, and agreed well with those fed and fasted humans. For one baboon that was not given its morning meal, plutonium absorption 2 h after the start of the active phase was the same as that in the 24 h fasted animals. In contrast, for baboons that received a morning meal, plutonium absorption did not rise to the value of 24 h fasted baboons even 8 h after the meal. We conclude that GI absorption values for plutonium and uranium in adult baboons are good estimates of the values in humans and that the values for the fasted condition should be used to set standards for oral exposure of persons in the workplace. (author)

  17. Effect of bread gluten content on gastrointestinal function: a crossover MRI study on healthy humans.

    Science.gov (United States)

    Coletta, Marina; Gates, Fred K; Marciani, Luca; Shiwani, Henna; Major, Giles; Hoad, Caroline L; Chaddock, Gemma; Gowland, Penny A; Spiller, Robin C

    2016-01-14

    Gluten is a crucial functional component of bread, but the effect of increasing gluten content on gastrointestinal (GI) function remains uncertain. Our aim was to investigate the effect of increasing gluten content on GI function and symptoms in healthy participants using the unique capabilities of MRI. A total of twelve healthy participants completed this randomised, mechanistic, open-label, three-way crossover study. On days 1 and 2 they consumed either gluten-free bread (GFB), or normal gluten content bread (NGCB) or added gluten content bread (AGCB). The same bread was consumed on day 3, and MRI scans were performed every 60 min from fasting baseline up to 360 min after eating. The appearance of the gastric chime in the images was assessed using a visual heterogeneity score. Gastric volumes, the small bowel water content (SBWC), colonic volumes and colonic gas content and GI symptoms were measured. Fasting transverse colonic volume after the 2-d preload was significantly higher after GFB compared with NGCB and AGCB with a dose-dependent response (289 (SEM 96) v. 212 (SEM 74) v. 179 (SEM 87) ml, respectively; P=0·02). The intragastric chyme heterogeneity score was higher for the bread with increased gluten (AGCB 6 (interquartile range (IQR) 0·5) compared with GFB 3 (IQR 0·5); P=0·003). However, gastric half-emptying time was not different between breads nor were study day GI symptoms, postprandial SBWC, colonic volume and gas content. This MRI study showed novel mechanistic insights in the GI responses to different breads, which are poorly understood notwithstanding the importance of this staple food.

  18. Relationship between postprandial motor activity in the human small intestine and the gastrointestinal transit of food

    Energy Technology Data Exchange (ETDEWEB)

    Read, N.W.; Al-Janabi, M.N.; Edwards, C.A.; Barber, D.C.

    1984-04-01

    Profiles for gastric emptying and colonic filling were determined in 20 normal volunteers by means of a gamma camera and dedicated minicomputer after ingestion of a radiolabeled solid meal. These were compared with intraluminal pressure activity, recorded simultaneously from three sites (each separated by 50 cm) in the small intestine by infusion manometry. Recordings were continued for at least 8 h or until all the radioactivity appeared in the colon. Colonic filling was approximately linear, occurring at an average rate of 16% of the meal residues per hour. There were significant inverse correlations (p less than 0.01) between the pressure activity in the proximal jejunum during the first 3 h after ingestion and the times taken for 50% and 80% of the meal residues to enter the colon, and direct correlations between total small intestinal pressure activity and the half-time for gastric emptying. Phase III of the interdigestive migrating motor complex appeared between 3 and 9 h after ingestion (when between 15% and 80% of the meal remained in the small intestine), but did not necessarily migrate to the next recording site until much later. The time of appearance of phase III in the proximal jejunum was directly correlated with the half-time for gastric emptying (p less than 0.05) and with the intraluminal pressure activity recorded at that site during the first 3 h after food ingestion (p less than 0.01). The time at which 80% of the meal residues had entered the colon was significantly shorter in 6 subjects, in whom a postprandial activity front appeared to migrate throughout the small bowel, compared with 13 subjects, in whom this did not occur (5.0 +/- 0.5 h vs. 7.0 +/- 0.4 h, p less than 0.01). These studies have shown that gastrointestinal transit of a solid meal is related to both fed and fasted intraluminal pressure activity in the small intestine.

  19. Gastrointestinal tuberculosis.

    Science.gov (United States)

    Galloway, D J; Scott, R N

    1986-10-01

    In the developed countries gastrointestinal tuberculosis is no longer common in clinical practice. In this setting the importance of the condition lies in the vagaries of its presentation and the fact that it is eminently treatable, usually by a combination of chemotherapy and surgery. The clinical features and complications of gastrointestinal tuberculosis are highlighted by the seven cases which we report. Diagnosis and treatment of this condition is discussed and attention is drawn to the importance of case notification. Clinicians should bear in mind the diagnosis of gastrointestinal tuberculosis when dealing with any patient with non-specific abdominal symptoms.

  20. High-resolution imaging of the layers of the gastrointestinal wall of pig and human specimens using an endoluminal MR receiver coil. Correlation to histology

    International Nuclear Information System (INIS)

    Kramer, Sebastian; Palmowski, M.; Macher-Goeppinger, S.; Mueller, M.; Volke, F.; Duex, M.; Kauczor, H.U.; Grenacher, L.

    2009-01-01

    Purpose: High-resolution MR imaging of the layers of the gastrointestinal wall to provide a foundation for tumor staging based on morphological criteria. Materials and Methods: Over a period of 12 months, miscellaneous parts of the gastrointestinal tract of 15 human specimens and 30 porcine specimens were scanned using a 1.5 Tesla clinical MRI scanner combined with an endoluminal receiver coil. The sequences used were T1-weighted opposed-phase, T2-weighted turbo spin echo with fat saturation and fast T2-weighted inversion recovery. The number of differentiable layers, their width and the signal intensity were documented. Then, the results were compared with histological specimens in order to link the imaged wall layers to the anatomical layers. Spearman's Rank Correlation was used to determine the soundness of the link between the images and their related histology. Results: For both human and animal specimens, the MRI scanning produced 3 to 5, maximum 6 (pig), differentiable layers. The mucosa, submucosa and muscularis could be differentiated with a hyperintense, hypointense and intermediary signal, respectively. The subserosal layer displayed a hypointense signal. Conclusion: High-resolution MRI is able to produce differentiable images of the anatomical layers of the gastrointestinal wall in both humans and pigs. Accordingly, it is possible to use MR imaging to diagnose the extent of local tumor infiltration of the gastrointestinal wall. (orig.)

  1. A Method for Quantification of Epithelium Colonization Capacity by Pathogenic Bacteria

    DEFF Research Database (Denmark)

    Micha Pedersen, Rune; Grønnemose, Rasmus Birkholm; Stærk, Kristian

    2018-01-01

    a method in which epithelia/endothelia are simulated by flow chamber-grown human cell layers, and infection is induced by seeding of pathogenic bacteria on these surfaces under conditions that simulate the physiological microenvironment. Quantification of bacterial adhesion and colonization of the cell......Most bacterial infections initiate at the mucosal epithelium lining the gastrointestinal, respiratory, and urogenital tracts. At these sites, bacterial pathogens must adhere and increase in numbers to effectively breach the outer barrier and invade the host. If the bacterium succeeds in reaching...... the bloodstream, effective dissemination again requires that bacteria in the blood, reestablish contact to distant endothelium sites and form secondary site foci. The infectious potential of bacteria is therefore closely linked to their ability to adhere to, colonize, and invade epithelial and endothelial...

  2. Gastrointestinal bleeding

    Science.gov (United States)

    ... Sigmoidoscopy Alternative Names Lower GI bleeding; GI bleeding; Upper GI bleeding; Hematochezia Images GI bleeding - series Fecal occult blood test References Kovacs TO, Jensen DM. Gastrointestinal hemorrhage. In: Goldman L, Schafer AI, eds. Goldman- ...

  3. Comparison of Nitrogen Bioaccessibility from Salmon and Whey Protein Hydrolysates using a Human Gastrointestinal Model (TIM-1

    Directory of Open Access Journals (Sweden)

    Bomi Framroze

    2014-05-01

    Full Text Available Background: The TIM-1 system is a computer-controlled multi-compartmental dynamic model that closely simulates in vivo gastrointestinal tract digestion in humans. During digestion, the compounds released from meal matrix by gastric and intestinal secretions (enzymes are progressively absorbed through semipermeable membranes depending on their molecular weight. These absorbed (dialysed compounds are considered as bioaccessible, which means that they can be theoretically absorbed by the small intestine in the body. Methods: Salmon protein hydrolysate (SPH, whey protein hydrolysates extensively (WPHHigh or weakly (WPH-Low hydrolysed, non-hydrolysed whey protein isolate (WPI and mixtures of WPI:SPH (90:10, 80:20 were digested in TIM-1 using the conditions for a fast gastrointestinal transit that simulate the digestion of a liquid meal in human adults. During digestion (2 hours, samples were collected in intestinal compartments (duodenum, jejunum, and ileum and in both jejunal and ileal dialysates to determine their nitrogen content. All the products were compared in terms of kinetics of nitrogen absorption through the semipermeable membranes (bioaccessible nitrogen and nitrogen distribution throughout the intestinal compartments at the end of the 2 hour digestion. Results: After a 2 h-digestion in TIM-1, SPH was the protein substrate from which the highest amount of nitrogen (67.0% becomes available for the small intestine absorption. WPH-High had the second highest amount (56.0% of bioaccessible nitrogen while this amount decreased to 38.5–42.2% for the other protein substrates. The high nitrogen bioaccessibility of SPH is consistent with its richness in low molecular weight peptides (50% < 1000 Da. Conclusions: The results of this study indicate that SPH provides a higher proportion of bioaccessible nitrogen to a healthy adult compared to all forms of whey proteins, including extensively hydrolysed whey protein hydrolysate. The substitution of

  4. The dose-response relation in human volunteers for gastro-intestinal pathogens

    NARCIS (Netherlands)

    Teunis PFM; Heijden OG van der; Giessen JWB van der; Havelaar AH; MGB

    1996-01-01

    Published data on infection of human hosts with various protozoa, bacteria, and viruses causing gastro-enteritis are used to establish a quantitative relationship between ingested dose and the risk of infection. For all data sets analysed, this relationship is determined by fitting either an

  5. In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract

    Science.gov (United States)

    Piyawattanametha, Wibool; Ra, Hyejun; Qiu, Zhen; Friedland, Shai; Liu, Jonathan T. C.; Loewke, Kevin; Kino, Gordon S.; Solgaard, Olav; Wang, Thomas D.; Mandella, Michael J.; Contag, Christopher H.

    2012-02-01

    Near-infrared confocal microendoscopy is a promising technique for deep in vivo imaging of tissues and can generate high-resolution cross-sectional images at the micron-scale. We demonstrate the use of a dual-axis confocal (DAC) near-infrared fluorescence microendoscope with a 5.5-mm outer diameter for obtaining clinical images of human colorectal mucosa. High-speed two-dimensional en face scanning was achieved through a microelectromechanical systems (MEMS) scanner while a micromotor was used for adjusting the axial focus. In vivo images of human patients are collected at 5 frames/sec with a field of view of 362×212 μm2 and a maximum imaging depth of 140 μm. During routine endoscopy, indocyanine green (ICG) was topically applied a nonspecific optical contrasting agent to regions of the human colon. The DAC microendoscope was then used to obtain microanatomic images of the mucosa by detecting near-infrared fluorescence from ICG. These results suggest that DAC microendoscopy may have utility for visualizing the anatomical and, perhaps, functional changes associated with colorectal pathology for the early detection of colorectal cancer.

  6. CD34 immunoreactivity and interstitial cells of Cajal in the human and mouse gastrointestinal tract

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J; De Laet, M H

    2000-01-01

    , we observed that CD34-ir labeled Kit-negative fibroblast-like cells, closely adjacent to, but distinct from, the Kit-ir ICC. The existence of cells expressing both CD34-ir and Kit-ir remains controversial. CD34-ir and Kit-ir were studied by high-resolution confocal microscopy on cryostat sections...... of human and murine gut as well as murine whole-mounts, using specific antibodies raised to human and murine CD34, respectively. CD34-ir labeled numerous cells in all parts of the gut, in man and in mouse. CD34-ir was consistently observed in Kit-negative cells, distinct from the closely adjacent Kit......-ir ICC. Thin processes of both cell types intermingled extensively, often at the limit of resolution for light microscopy. CD34-ir was also observed in Kit-negative mesenchymal cells in the submucosa, in capillaries and in mesothelial cells. CD34-ir is not a marker for Kit-ir ICC in the human and murine...

  7. Colonizing the embryonic zebrafish gut with anaerobic bacteria derived from the human gastrointestinal tract.

    Science.gov (United States)

    Toh, Michael C; Goodyear, Mara; Daigneault, Michelle; Allen-Vercoe, Emma; Van Raay, Terence J

    2013-06-01

    The zebrafish has become increasingly popular for microbiological research. It has been used as an infection model for a variety of pathogens, and is also emerging as a tool for studying interactions between a host and its resident microbial communities. The mouse microbiota has been transplanted into the zebrafish gut, but to our knowledge, there has been no attempt to introduce a bacterial community derived from the human gut. We explored two methods for colonizing the developing gut of 5-day-old germ-free zebrafish larvae with a defined anaerobic microbial community derived from a single human fecal sample. Both environmental exposure (static immersion) and direct microinjection into the gut resulted in the establishment of two species-Lactobacillus paracasei and Eubacterium limosum-from a community of 30 strains consisting of 22 anaerobic species. Of particular interest is E. limosum, which, as a strict anaerobe, represents a group of bacteria which until now have not been shown to colonize the developing zebrafish gut. Our success here indicates that further investigation of zebrafish as a tool for studying human gut microbial communities is warranted.

  8. Aspects of gastrointestinal immunology and nutrition in human immunodeficiency virus-1 infection in Brazil

    Directory of Open Access Journals (Sweden)

    Castello-Branco Luiz RR

    2000-01-01

    Full Text Available Mucosal surfaces have a fundamental participation in many aspects of the human immunodeficiency virus (HIV infection pathogenesis. In Brazilian HIV-1 infected subjects, loss of weight and appetite are among the most debilitating symptoms. In this review we describe a defined mucosal immunogen that has profound but transient effects on HIV viral load, and we suggest that gut associated lymphoid tissue under constant immunostimulation is likely to provide a major contribution to the total levels of HIV. We also show that hypermetabolism appears to play a role in the wasting process in Brazilian patients coinfected with HIV and tuberculosis.

  9. Barrier properties of cultured retinal pigment epithelium.

    Science.gov (United States)

    Rizzolo, Lawrence J

    2014-09-01

    The principal function of an epithelium is to form a dynamic barrier that regulates movement between body compartments. Each epithelium is specialized with barrier functions that are specific for the tissues it serves. The apical surface commonly faces a lumen, but the retinal pigment epithelium (RPE) appears to be unique by a facing solid tissue, the sensory retina. Nonetheless, there exists a thin (subretinal) space that can become fluid filled during pathology. RPE separates the subretinal space from the blood supply of the outer retina, thereby forming the outer blood-retinal barrier. The intricate interaction between the RPE and sensory retina presents challenges for learning how accurately culture models reflect native behavior. The challenge is heightened by findings that detail the variation of RPE barrier proteins both among species and at different stages of the life cycle. Among the striking differences is the expression of claudin family members. Claudins are the tight junction proteins that regulate ion diffusion across the spaces that lie between the cells of a monolayer. Claudin expression by RPE varies with species and life-stage, which implies functional differences among commonly used animal models. Investigators have turned to transcriptomics to supplement functional studies when comparing native and cultured tissue. The most detailed studies of the outer blood-retinal barrier have focused on human RPE with transcriptome and functional studies reported for human fetal, adult, and stem-cell derived RPE. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Study of the gastrointestinal parasitic fauna of captive non-human primates (Macaca fascicularis).

    Science.gov (United States)

    Zanzani, Sergio Aurelio; Gazzonis, Alessia Libera; Epis, Sara; Manfredi, Maria Teresa

    2016-01-01

    The aim of this study was to examine helminths and protozoans in cynomolgus macaques (Macaca fascicularis) imported from registered breeding facilities in China and their relation to health risks for non-human primate handlers in biomedical research centers and in breeding facilities. Fresh fecal samples were collected from a total of 443 M. fascicularis and analyzed by copromicroscopical analysis, immunoenzymatic, or molecular assays. As to helminths, whose eggs were shed in 2.03% of the samples, Trichuris and Oesophagostomum were the only two taxa found, with low prevalence and low eggs per gram (EPG) values. Protozoans were more frequently detected (87.40%), with Entamoeba coli (85.19%) and Endolimax nana (79.26%) as the most prevalent species shed. Other parasites found by fecal smear examination were uninucleated-cyst-producing Entamoebas (78.52%), Iodamoeba bütschlii (42.96%), and Chilomastix mesnili (24.44%), while cysts of Balantidium coli (22.2%) were only observed by sedimentation. No coproantigens of Giardia duodenalis, Cryptosporidium spp., and Entamoeba histolytica complex were detected. Blastocystis sp. infection was noticed in 87.63% of macaques by PCR. These cynomolgus monkeys were infected with many subtypes (ST1, ST2, ST3, ST5, and ST7), where the predominant Blastocystis sp. subtypes were ST2 (77.5%), followed by ST1 (63.5%). Data collected confirmed the presence of potentially zoonotic parasites and a high parasite diversity, suggesting the need for appropriate and sensitive techniques to adequately control them and related health risks for handlers of non-human primates in biomedical research centers and in breeding facilities.

  11. [The identification of viruses of human papilloma of high carcinogenic risk and evaluation of physical status of viral DNA using technique of polymerase-chain reaction under affection of cervical epithelium].

    Science.gov (United States)

    Viazovaia, A A; Kuevda, D A; Trofimova, O B; Shipulina, O Iu; Ershov, V A; Lialina, L V; Narvskaia, O V

    2013-08-01

    The DNA of virus of human papilloma of high carcinogenic risk was detected in 116 cervical samples. At that, the morphological symptoms of background processes are detected in 19 samples, CIN 1 in 9, CIN 2 in 23, CIN 3 in 54 (and out of them carcinoma in situ in 13), epidermoid cancer (squamous cell carcinoma) in 11 cases. The viral load of human papilloma of high carcinogenic risk in all samples of DNA exceeded threshold of clinical value (3 lg copies of DNA of human papilloma/105 cells). The genetic typing of human papilloma of high carcinogenic risk revealed the dominance of human papilloma of type 16 in 49.7%, type 33 in 15.3%, type 31 in 12.3% and type 45 in 5.5%. In women with background processes in cervix of the uterus DNA of human papilloma type 16 was detected more often in episome form. In case of dysplastic alterations of epithelium and cervical cancer DNA of human papilloma type 16 is detected in mixt form with different degree of integration into cell genome.

  12. Gastrointestinal and ectoparasites from urban stray dogs in Fortaleza (Brazil): high infection risk for humans?

    Science.gov (United States)

    Klimpel, Sven; Heukelbach, Jörg; Pothmann, David; Rückert, Sonja

    2010-08-01

    Dogs are important definite or reservoir hosts for zoonotic parasites. However, only few studies on the prevalence of intestinal parasites in urban areas in Brazil are available. We performed a comprehensive study on parasites of stray dogs in a Brazilian metropolitan area. We included 46 stray dogs caught in the urban areas of Fortaleza (northeast Brazil). After euthanization, dogs were autopsied. Ectoparasites were collected, and the intestinal content of dogs were examined for the presence of parasites. Faecal samples were collected and analysed using merthiolate iodine formaldehyde concentration method. A total of nine different parasite species were found, including five endoparasite (one protozoan, one cestode and three nematode species) and four ectoparasite species (two flea, one louse and one tick species). In the intestinal content, 3,162 specimens of four helminth species were found: Ancylostoma caninum (prevalence, 95.7%), Dipylidium caninum (45.7%), Toxocara canis (8.7%) and Trichuris vulpis (4.3%). A total of 394 ectoparasite specimens were identified, including Rhipicephalus sanguineus (prevalence, 100.0%), Heterodoxus spiniger (67.4%), Ctenocephalides canis (39.1%) and Ctenocephalides felis (17.4%). In the faeces, intestinal parasites were detected in 38 stray dogs (82.6%), including oocysts of Giardia sp. (2.2%) and eggs of the nematode A. caninum (82.6%). Neither eggs nor larval stages of D. caninum, T. canis or T. vulpis were detected in dog faeces. Sensitivity of faecal examination for A. caninum was 86.4% (95% confidence interval, 72.0-94.3) but zero percentage for the other intestinal helminth species. Our data show that stray dogs in northeast Brazil carry a multitude of zoonotic ecto- and endoparasites, posing a considerable risk for humans. With the exception of A. caninum, sensitivity of faecal examination was negligible.

  13. Gastrointestinal System

    NARCIS (Netherlands)

    Jepson, Mark A.; Bouwmeester, Hans

    2017-01-01

    The epithelial lining of the gastrointestinal tract (GIT) acts as a barrier to uptake of potentially dangerous material while allowing absorption of processed food. The gut may be exposed to a diverse range of engineered nanomaterials due to their deliberate addition to food and consumer products

  14. Coelomic epithelium-derived cells in visceral morphogenesis.

    Science.gov (United States)

    Ariza, Laura; Carmona, Rita; Cañete, Ana; Cano, Elena; Muñoz-Chápuli, Ramón

    2016-03-01

    Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans. © 2015 Wiley Periodicals, Inc.

  15. Development of the ovarian follicular epithelium.

    Science.gov (United States)

    Rodgers, R J; Lavranos, T C; van Wezel, I L; Irving-Rodgers, H F

    1999-05-25

    A lot is known about the endocrine control of the development of ovarian follicles, but a key question now facing researchers is which molecular and cellular processes take part in control of follicular growth and development. The growth and development of ovarian follicles occurs postnatally and throughout adult life. In this review, we focus on the follicular epithelium (membrana granulosa) and its basal lamina. We discuss a model of how granulosa cells arise from a population of stem cells and then enter different lineages before differentiation. The structure of the epithelium at the antral stage of development is presented, and the effects that follicle growth has on the behavior of the granulosa cells are discussed. Finally, we discuss the evidence that during follicle development the follicular basal lamina changes in composition. This would be expected if the behavior of the granulosa cells changes, or if the permeability of the basal lamina changes. It will be evident that the follicular epithelium has similarities to other epithelia in the body, but that it is more dynamic, as gross changes occur during the course of follicle development. This basic information will be important for the development of future reproductive technologies in both humans and animals, and possibly for understanding polycystic ovarian syndrome in women.

  16. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    OpenAIRE

    Barkla, D. H.; Whitehead, R. H.; Foster, H.; Tutton, P. J.

    1988-01-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting f...

  17. World Health Organisation Classification of Lymphoid Tumours in Veterinary and Human Medicine: a Comparative Evaluation of Gastrointestinal Lymphomas in 61 Cats.

    Science.gov (United States)

    Wolfesberger, B; Fuchs-Baumgartinger, A; Greß, V; Hammer, S E; Gradner, G; Knödl, K; Tichy, A; Rütgen, B C; Beham-Schmid, C

    2018-02-01

    To diagnose and classify the various entities of lymphomas, the World Health Organisation (WHO) classification is applied in human as well as in veterinary medicine. We validated the concordance of these classification systems by having a veterinary and human pathologist evaluate gastrointestinal lymphoma tissue from 61 cats. In 59% of all cases, there was a match between their respective diagnoses of the lymphoma subtype. A complete consensus between the two evaluators was obtained for all samples with a diagnosis of diffuse large B-cell lymphoma, T-cell anaplastic large cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. A corresponding diagnosis was also made in the majority of samples with enteropathy associated T-cell lymphoma (EATL) type II, although this subtype in cats has similarities to the 'indolent T-cell lymphoproliferative disorder of the gastrointestinal tract', a provisional entity newly added to the revised human WHO classification in 2016. Very little consensus has been found with cases of EATL type I due to the fact that most did not meet all of the criteria of human EATL I. Hence, the human pathologist assigned them to the heterogeneous group of peripheral T-cell lymphomas (not otherwise specified). Consequently, concrete guidelines and advanced immunophenotyping based on the model of human medicine are essential to differentiate these challenging entities in veterinary medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Anti-Infective Activities of Lactobacillus Strains in the Human Intestinal Microbiota: from Probiotics to Gastrointestinal Anti-Infectious Biotherapeutic Agents

    Science.gov (United States)

    Liévin-Le Moal, Vanessa

    2014-01-01

    SUMMARY A vast and diverse array of microbial species displaying great phylogenic, genomic, and metabolic diversity have colonized the gastrointestinal tract. Resident microbes play a beneficial role by regulating the intestinal immune system, stimulating the maturation of host tissues, and playing a variety of roles in nutrition and in host resistance to gastric and enteric bacterial pathogens. The mechanisms by which the resident microbial species combat gastrointestinal pathogens are complex and include competitive metabolic interactions and the production of antimicrobial molecules. The human intestinal microbiota is a source from which Lactobacillus probiotic strains have often been isolated. Only six probiotic Lactobacillus strains isolated from human intestinal microbiota, i.e., L. rhamnosus GG, L. casei Shirota YIT9029, L. casei DN-114 001, L. johnsonii NCC 533, L. acidophilus LB, and L. reuteri DSM 17938, have been well characterized with regard to their potential antimicrobial effects against the major gastric and enteric bacterial pathogens and rotavirus. In this review, we describe the current knowledge concerning the experimental antibacterial activities, including antibiotic-like and cell-regulating activities, and therapeutic effects demonstrated in well-conducted, placebo-controlled, randomized clinical trials of these probiotic Lactobacillus strains. What is known about the antimicrobial activities supported by the molecules secreted by such probiotic Lactobacillus strains suggests that they constitute a promising new source for the development of innovative anti-infectious agents that act luminally and intracellularly in the gastrointestinal tract. PMID:24696432

  19. Effects of ionizing radiation on glycerolated amniotic membranes as a substract for cultured human epithelium; Efeitos da radiacao ionizante em membranas amnioticas gliceroladas empregadas como substrato ao cultivo de epitelio humano

    Energy Technology Data Exchange (ETDEWEB)

    Paggiaro, Andre Oliveira

    2011-07-01

    The amniotic membrane (AM) is a biomaterial with biological properties that are beneficial to tissue repair. It has been used as a temporary coverage to threat burns and chronic wounds. Recently, it has been served as a substrate for keratinocytes culture to construct a living skin equivalent. However, MA is a biological material, and its transplantation could cause infectious disease for receptors. So, it must be preserved and sterilized before clinical use. The aim of this study was to evaluate the radiation effects on glycerol-preserved MA, considering its compatibility to support human keratinocytes culture. Four MA were stored in high concentrations of glycerol (> 85%) and half of them were radio sterilized with a dose of 25 kGy. Then, we established two groups: nonirradiated MA (MA-ni) and irradiated MA (MA-i). Both groups was deepithelialized by a standardized protocol and was investigated morphologically, immunohistochemical and ultrastructural. Subsequently human keratinocytes were cultivated immersed and in air-liquid interface on denuded surface of MA-i and MA-ni. The results were compared at 14 and 21 days of culture by light and electron microscopy. After epithelial denudation, analyses demonstrated the continuity of the basement membrane in MA-ni group, whereas in the irradiated group, there was no indication of the basement membrane’s presence on the surface of MA. The cell cultures showed that in the non-irradiated group, there was growth of a multi-layered and differentiated epithelium, with a stratum corneum’s formation in air-liquid interface. In the irradiated group, the epithelium had only two or three layer, little cell differentiation, with the same results immersed or air-liquid interface system. Glycerol-preserved MA was biocompatible with the growth of a cultivated epithelium, showing its potential as a skin substitute. Irradiation at 25 kGy cause structural damage to the tissue, making changes in basement membrane, that facilitates

  20. 重组人表皮生长因子对植皮创面成活的影响%Effect of recombinant human epithelium growth factor on livability of skin graft

    Institute of Scientific and Technical Information of China (English)

    龙剑虹; 张明华; 谢庭鸿; 杨兴华; 黄晓元; 周捷

    2003-01-01

    AIM: To investigate the effects of recombinant human epithelium growth factor (rhEGF) applied to skin graft. METHODS: 96 cases between February 2000 and December 2001, were treated. During the operation, After scar removed and skin grafted, the rhEGF was injected under the skin graft. 80 cases without injection of rhEGF were made as contrast. Ten days later, the area of survived skin was measured and the livability of skin was calculated. RESULTS: The skin livability of cases with injection of rhEGF was (90.67 ± 10.02)% and the skin livability of contrast cases was(76. 85 ± 8.35)%. There axisted evident differences between them( P < 0. 01) . CONCLUSION: The rhEGF was an effective method for increasing livability of skin graft.

  1. Calculation by the Monte Carlo method of the equivalent dose received by a human fetus from gamma sources localized in the gastrointestinal tract

    International Nuclear Information System (INIS)

    Segreto, V.S.A.

    1979-01-01

    New uterus positions are proposed and worked out in detail to evaluate the exposure of the human fetus to radiation originated in the gastrointestinal-tract during the pregnancy period. In our evaluation each organ in the gastrointestinal-tract namely stomach, small intestine, transverse colon, ascendent colon, descendent colon, sigmoid and rectum was individually considered. Changes in the position of each of these organs were studied as a function of the uterus growth. There were evaluated cases in which the uterus was in three, six and nine month pregnancy for photon energies of 0.02, 0.05, 0.10, 0.50 and 4 MeV. The average equivalent doses (H) of the uterus, in the uterine wall and in each one of the twelve compartiments which we considered as sub-divisions of the uterus were also determined and discussed. (Auhor) [pt

  2. Prevalence of gastrointestinal parasites in captive non-human primates of twenty-four zoological gardens in China.

    Science.gov (United States)

    Li, Mei; Zhao, Bo; Li, Bo; Wang, Qiang; Niu, Lili; Deng, Jiabo; Gu, Xiaobin; Peng, Xuerong; Wang, Tao; Yang, Guangyou

    2015-06-01

    Captive primates are susceptible to gastrointestinal (GIT) parasitic infections, which are often zoonotic and can contribute to morbidity and mortality. Fecal samples were examined by the means of direct smear, fecal flotation, fecal sedimentation, and fecal cultures. Of 26.51% (317/1196) of the captive primates were diagnosed gastrointestinal parasitic infections. Trichuris spp. were the most predominant in the primates, while Entamoeba spp. were the most prevalent in Old World monkeys (P primates and the safety of animal keepers and visitors. © 2015 The Authors. Journal of Medical Primatology Published by John Wiley & Sons Ltd.

  3. Survival of Lactobacillus reuteri DSM 17938 and Lactobacillus rhamnosus GG in the human gastrointestinal tract with daily consumption of a low-fat probiotic spread.

    Science.gov (United States)

    Dommels, Yvonne E M; Kemperman, Robèr A; Zebregs, Yvonne E M P; Draaisma, René B; Jol, Arne; Wolvers, Danielle A W; Vaughan, Elaine E; Albers, Ruud

    2009-10-01

    Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. Therefore, probiotic strains should be able to survive passage through the human gastrointestinal tract. Human gastrointestinal tract survival of probiotics in a low-fat spread matrix has, however, never been tested. The objective of this randomized, double-blind, placebo-controlled human intervention study was to test the human gastrointestinal tract survival of Lactobacillus reuteri DSM 17938 and Lactobacillus rhamnosus GG after daily consumption of a low-fat probiotic spread by using traditional culturing, as well as molecular methods. Forty-two healthy human volunteers were randomly assigned to one of three treatment groups provided with 20 g of placebo spread (n = 13), 20 g of spread with a target dose of 1 x 10(9) CFU of L. reuteri DSM 17938 (n = 13), or 20 g of spread with a target dose of 5 x 10(9) CFU of L. rhamnosus GG (n = 16) daily for 3 weeks. Fecal samples were obtained before and after the intervention period. A significant increase, compared to the baseline, in the recovery of viable probiotic lactobacilli in fecal samples was demonstrated after 3 weeks of daily consumption of the spread containing either L. reuteri DSM 17938 or L. rhamnosus GG by selective enumeration. In the placebo group, no increase was detected. The results of selective enumeration were supported by quantitative PCR, detecting a significant increase in DNA resulting from the probiotics after intervention. Overall, our results indicate for the first time that low-fat spread is a suitable carrier for these probiotic strains.

  4. Human adipose-derived mesenchymal stromal cell pigment epithelium-derived factor cytotherapy modifies genetic and epigenetic profiles of prostate cancer cells.

    Science.gov (United States)

    Zolochevska, Olga; Shearer, Joseph; Ellis, Jayne; Fokina, Valentina; Shah, Forum; Gimble, Jeffrey M; Figueiredo, Marxa L

    2014-03-01

    Adipose-derived mesenchymal stromal cells (ASCs) are promising tools for delivery of cytotherapy against cancer. However, ASCs can exert profound effects on biological behavior of tumor cells. Our study aimed to examine the influence of ASCs on gene expression and epigenetic methylation profiles of prostate cancer cells as well as the impact of expressing a therapeutic gene on modifying the interaction between ASCs and prostate cancer cells. ASCs were modified by lentiviral transduction to express either green fluorescent protein as a control or pigment epithelium-derived factor (PEDF) as a therapeutic molecule. PC3 prostate cancer cells were cultured in the presence of ASC culture-conditioned media (CCM), and effects on PC3 or DU145. Ras cells were examined by means of real-time quantitative polymerase chain reaction, EpiTect methyl prostate cancer-focused real-time quantitative polymerase chain reaction arrays, and luciferase reporter assays. ASCs transduced with lentiviral vectors were able to mediate expression of several tumor-inhibitory genes, some of which correlated with epigenetic methylation changes on cocultured PC3 prostate cancer cells. When PC3 cells were cultured with ASC-PEDF CCM, we observed a shift in the balance of gene expression toward tumor inhibition, which suggests that PEDF reduces the potential tumor-promoting activity of unmodified ASCs. These results suggest that ASC-PEDF CCM can promote reprogramming of tumor cells in a paracrine manner. An improved understanding of genetic and epigenetic events in prostate cancer growth in response to PEDF paracrine therapy would enable a more effective use of ASC-PEDF, with the goal of achieving safer yet more potent anti-tumor effects. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  5. Angiotensin I-Converting Enzyme (ACE Inhibitory Activity and ACE Inhibitory Peptides of Salmon (Salmo salar Protein Hydrolysates Obtained by Human and Porcine Gastrointestinal Enzymes

    Directory of Open Access Journals (Sweden)

    Małgorzata Darewicz

    2014-08-01

    Full Text Available The objectives of the present study were two-fold: first, to detect whether salmon protein fractions possess angiotensin I-converting enzyme (ACE inhibitory properties and whether salmon proteins can release ACE inhibitory peptides during a sequential in vitro hydrolysis (with commercial porcine enzymes and ex vivo digestion (with human gastrointestinal enzymes. Secondly, to evaluate the ACE inhibitory activity of generated hydrolysates. A two-step ex vivo and in vitro model digestion was performed to simulate the human digestion process. Salmon proteins were degraded more efficiently by porcine enzymes than by human gastrointestinal juices and sarcoplasmic proteins were digested/hydrolyzed more easily than myofibrillar proteins. The ex vivo digested myofibrillar and sarcoplasmic duodenal samples showed IC50 values (concentration required to decrease the ACE activity by 50% of 1.06 and 2.16 mg/mL, respectively. The in vitro hydrolyzed myofibrillar and sarcoplasmic samples showed IC50 values of 0.91 and 1.04 mg/mL, respectively. Based on the results of in silico studies, it was possible to identify 9 peptides of the ex vivo hydrolysates and 7 peptides of the in vitro hydrolysates of salmon proteins of 11 selected peptides. In both types of salmon hydrolysates, ACE-inhibitory peptides IW, IY, TVY and VW were identified. In the in vitro salmon protein hydrolysates an ACE-inhibitory peptides VPW and VY were also detected, while ACE-inhibitory peptides ALPHA, IVY and IWHHT were identified in the hydrolysates generated with ex vivo digestion. In our studies, we documented ACE inhibitory in vitro effects of salmon protein hydrolysates obtained by human and as well as porcine gastrointestinal enzymes.

  6. In Vivo Dissolution and Systemic Absorption of Immediate Release Ibuprofen in Human Gastrointestinal Tract under Fed and Fasted Conditions.

    Science.gov (United States)

    Koenigsknecht, Mark J; Baker, Jason R; Wen, Bo; Frances, Ann; Zhang, Huixia; Yu, Alex; Zhao, Ting; Tsume, Yasuhiro; Pai, Manjunath P; Bleske, Barry E; Zhang, Xinyuan; Lionberger, Robert; Lee, Allen; Amidon, Gordon L; Hasler, William L; Sun, Duxin

    2017-12-04

    In vivo drug dissolution in the gastrointestinal (GI) tract is largely unmeasured. The purpose of this clinical study was to evaluate the in vivo drug dissolution and systemic absorption of the BCS class IIa drug ibuprofen under fed and fasted conditions by direct sampling of stomach and small intestinal luminal content. Expanding current knowledge of drug dissolution in vivo will help to establish physiologically relevant in vitro models predictive of drug dissolution. A multilumen GI catheter was orally inserted into the GI tract of healthy human subjects. Subjects received a single oral dose of ibuprofen (800 mg tablet) with 250 mL of water under fasting and fed conditions. The GI catheter facilitated collection of GI fluid from the stomach, duodenum, and jejunum. Ibuprofen concentration in GI fluid supernatant and plasma was determined by LC-MS/MS. A total of 23 subjects completed the study, with 11 subjects returning for an additional study visit (a total of 34 completed study visits). The subjects were primarily white (61%) and male (65%) with an average age of 30 years. The subjects had a median [min, max] weight of 79 [52, 123] kg and body mass index of 25.7 [19.4, 37.7] kg/m 2 . Ibuprofen plasma levels were higher under fasted conditions and remained detectable for 28 h under both conditions. The AUC 0-24 and C max were lower in fed subjects vs fasted subjects, and T max was delayed in fed subjects vs fasted subjects. Ibuprofen was detected immediately after ingestion in the stomach under fasting and fed conditions until 7 h after dosing. Higher levels of ibuprofen were detected in the small intestine soon after dosing in fasted subjects compared to fed. In contrast to plasma drug concentration, overall gastric concentrations remained higher under fed conditions due to increased gastric pH vs fasting condition. The gastric pH increased to near neutrality after feedingbefore decreasing to acidic levels after 7 h. Induction of the fed state reduced systemic

  7. gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Rolandas Vaicekauskas

    2016-07-01

    Full Text Available Introduction : Accurate diagnosis of subepithelial lesions (SELs in the gastrointestinal tract depends on a variety of methods: endoscopy, endoscopic ultrasound and different types of biopsy. Making an error-free diagnosis is vital for the subsequent application of an appropriate treatment. Aim: To evaluate the efficacy of deep biopsy via the endoscopic submucosal dissection (ESD technique for SELs in the upper gastrointestinal tract. Material and methods: It was a case series study. Deep biopsy via the ESD technique was completed in 38 patients between November 2012 and October 2014. Thirty-eight SELs in the upper gastrointestinal tract of varying size (very small ≤ 1 cm, small 1–2 cm and large ≥ 2 cm by means of the ESD technique after an incision with an electrosurgical knife of the overlying layers and revealing a small part of the lesion were biopsied under direct endoscopic view. Results: Deep biopsy via the ESD technique was diagnostic in 28 of 38 patients (73.3%; 95% CI: 59.7–89.7%. The diagnostic yield for SELs with a clear endophytic shape increased to 91.3%. An evident endophytic appearance of a subepithelial lesion, the mean number of biopsied samples (6.65 ±1.36 and the total size in length of all samples per case (19.88 ±8.07 mm were the main criteria influencing the positiveness of deep biopsy in the diagnostic group compared to the nondiagnostic one (p = 0.001; p = 0.025; p = 0.008. Conclusions : Deep biopsy via the ESD technique is an effective and safe method for the diagnosis of SELs especially with a clear endophytic appearance in a large number of biopsied samples.

  8. Enzyme activity of β-galactosidase from Kluyveromyces lactis and Aspergillus oryzae on simulated conditions of human gastrointestinal system

    Directory of Open Access Journals (Sweden)

    Alessandra Bosso

    2015-09-01

    Full Text Available An alternative to relieve the symptoms of lactose intolerance is the intake of the enzyme β-galactosidase in pharmaceutical dosage forms. The ability of β-galactosidase produced by Kluyveromyces lactis and Aspergillus oryzae to hydrolyze lactose in simulated conditions of the human gastrointestinal tract was investigated. The experiment was carried out in the optimum temperature for each enzyme activity, 40 and 55°C, respectively, and at the normal human body temperature (37°C at concentrations of 1.5, 3.0, and 5.0 g/L (enzyme from A. oryzae or mL/L (enzyme from K. lactis. Both enzymes were completely inactivated under simulated gastric conditions (pH 2. When the enzymes were subjected to simulated small intestine conditions (pH 7.4, lactose hydrolysis has occurred, but at 37°C the percentage was lower than that under the optimal temperatures. At concentrations of 1.5, 3.0, and 5.0 mL/L the enzyme from K. lactis hydrolyzed 76.63%, 88.91% and 94.80% of lactose at 40°C, and 55.99%, 80.91% and 81.53% at 37°C, respectively. In contrast, the enzyme from A. oryzae hydrolyzed 7.11%, 16.18% and 21.29% at 55°C, and 8.4%, 11.85% and 16.43% at 37°C. It was observed that under simulated intestinal conditions, the enzyme from K. lactis was more effective on lactose hydrolysis as compared to the enzyme from A. oryzae. Considering the findings of this study, it is extremely necessary to use an enteric coating on β-galactosidase capsules so that this enzyme is released only in the small intestine, which is its site of action, thus not suffering the action of the stomach pH.Keywords: Lactase. Hydrolysis. Lactose intolerance. Gastrointestinal tract. RESUMOAtividade de β-galactosidase de Kluyveromyces lactis e Aspergillus oryzae, em condições simuladas do sistema gastrintestinal humanoUma das alternativas para amenizar os sintomas da intolerância à lactose é a ingestão de β-galactosidase em formas farmacêuticas. Neste trabalho avaliou-se a

  9. Bacterial Composition of the Human Upper Gastrointestinal Tract Microbiome Is Dynamic and Associated with Genomic Instability in a Barrett's Esophagus Cohort.

    Directory of Open Access Journals (Sweden)

    Alevtina Gall

    Full Text Available The incidence of esophageal adenocarcinoma (EAC has increased nearly five-fold over the last four decades in the United States. Barrett's esophagus, the replacement of the normal squamous epithelial lining with a mucus-secreting columnar epithelium, is the only known precursor to EAC. Like other parts of the gastrointestinal (GI tract, the esophagus hosts a variety of bacteria and comparisons among published studies suggest bacterial communities in the stomach and esophagus differ. Chronic infection with Helicobacter pylori in the stomach has been inversely associated with development of EAC, but the mechanisms underlying this association remain unclear.The bacterial composition in the upper GI tract was characterized in a subset of participants (n=12 of the Seattle Barrett's Esophagus Research cohort using broad-range 16S PCR and pyrosequencing of biopsy and brush samples collected from squamous esophagus, Barrett's esophagus, stomach corpus and stomach antrum. Three of the individuals were sampled at two separate time points. Prevalence of H. pylori infection and subsequent development of aneuploidy (n=339 and EAC (n=433 was examined in a larger subset of this cohort.Within individuals, bacterial communities of the stomach and esophagus showed overlapping community membership. Despite closer proximity, the stomach antrum and corpus communities were less similar than the antrum and esophageal samples. Re-sampling of study participants revealed similar upper GI community membership in two of three cases. In this Barrett's esophagus cohort, Streptococcus and Prevotella species dominate the upper GI and the ratio of these two species is associated with waist-to-hip ratio and hiatal hernia length, two known EAC risk factors in Barrett's esophagus. H. pylori-positive individuals had a significantly decreased incidence of aneuploidy and a non-significant trend toward lower incidence of EAC.

  10. Bacterial Composition of the Human Upper Gastrointestinal Tract Microbiome Is Dynamic and Associated with Genomic Instability in a Barrett’s Esophagus Cohort

    Science.gov (United States)

    Gall, Alevtina; Fero, Jutta; McCoy, Connor; Claywell, Brian C.; Sanchez, Carissa A.; Blount, Patricia L.; Li, Xiaohong; Vaughan, Thomas L.; Matsen, Frederick A.; Reid, Brian J.; Salama, Nina R.

    2015-01-01

    Background The incidence of esophageal adenocarcinoma (EAC) has increased nearly five-fold over the last four decades in the United States. Barrett’s esophagus, the replacement of the normal squamous epithelial lining with a mucus-secreting columnar epithelium, is the only known precursor to EAC. Like other parts of the gastrointestinal (GI) tract, the esophagus hosts a variety of bacteria and comparisons among published studies suggest bacterial communities in the stomach and esophagus differ. Chronic infection with Helicobacter pylori in the stomach has been inversely associated with development of EAC, but the mechanisms underlying this association remain unclear. Methodology The bacterial composition in the upper GI tract was characterized in a subset of participants (n=12) of the Seattle Barrett’s Esophagus Research cohort using broad-range 16S PCR and pyrosequencing of biopsy and brush samples collected from squamous esophagus, Barrett’s esophagus, stomach corpus and stomach antrum. Three of the individuals were sampled at two separate time points. Prevalence of H. pylori infection and subsequent development of aneuploidy (n=339) and EAC (n=433) was examined in a larger subset of this cohort. Results/Significance Within individuals, bacterial communities of the stomach and esophagus showed overlapping community membership. Despite closer proximity, the stomach antrum and corpus communities were less similar than the antrum and esophageal samples. Re-sampling of study participants revealed similar upper GI community membership in two of three cases. In this Barrett’s esophagus cohort, Streptococcus and Prevotella species dominate the upper GI and the ratio of these two species is associated with waist-to-hip ratio and hiatal hernia length, two known EAC risk factors in Barrett’s esophagus. H. pylori-positive individuals had a significantly decreased incidence of aneuploidy and a non-significant trend toward lower incidence of EAC. PMID:26076489

  11. Gastrointestinal Traumatic Injuries: Gastrointestinal Perforation.

    Science.gov (United States)

    Revell, Maria A; Pugh, Marcia A; McGhee, Melanie

    2018-03-01

    The abdomen is a big place even in a small person. Gastrointestinal trauma can result in injury to the stomach, small bowel, colon, or rectum. Traumatic causes include blunt or penetrating trauma, such as gunshot wounds, stabbings, motor vehicle collisions, and crush injuries. Nontraumatic causes include appendicitis, Crohn disease, cancer, diverticulitis, ulcerative colitis, blockage of the bowel, and chemotherapy. The mechanism of injury will affect both the nature and severity of any resulting injuries. Treatment must address the critical and emergent nature of these injuries as well as issues that affect all trauma situations, which include management of hemodynamic instability. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Prevalence of ciliated epithelium in apical periodontitis lesions.

    Science.gov (United States)

    Ricucci, Domenico; Loghin, Simona; Siqueira, José F; Abdelsayed, Rafik A

    2014-04-01

    This article reports on the morphologic features and the frequency of ciliated epithelium in apical cysts and discusses its origin. The study material consisted of 167 human apical periodontitis lesions obtained consecutively from patients presenting for treatment during a period of 12 years in a dental practice operated by one of the authors. All of the lesions were obtained still attached to the root apices of teeth with untreated (93 lesions) or treated canals (74 lesions). The former were obtained by extraction and the latter by extraction or apical surgery. Specimens were processed for histopathologic and histobacteriologic analyses. Lesions were classified, and the type of epithelium, if present, was recorded. Of the lesions analyzed, 49 (29%) were diagnosed as cysts. Of these, 26 (53%) were found in untreated teeth, and 23 (47%) related to root canal-treated teeth. Ciliated columnar epithelium was observed partially or completely lining the cyst wall in 4 cysts, and all of them occurred in untreated maxillary molars. Three of these lesions were categorized as pocket cysts, and the other was a true cyst. Ciliated columnar epithelium-lined cysts corresponded to approximately 2% of the apical periodontitis lesions and 8% of the cysts of endodontic origin in the population studied. This epithelium is highly likely to have a sinus origin in the majority of cases. However, the possibility of prosoplasia or upgraded differentiation into ciliated epithelium from the typical cystic lining squamous epithelium may also be considered. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  13. Metabolism of vertebrate amino sugars with N-glycolyl groups: mechanisms underlying gastrointestinal incorporation of the non-human sialic acid xeno-autoantigen N-glycolylneuraminic acid.

    Science.gov (United States)

    Banda, Kalyan; Gregg, Christopher J; Chow, Renee; Varki, Nissi M; Varki, Ajit

    2012-08-17

    Although N-acetyl groups are common in nature, N-glycolyl groups are rare. Mammals express two major sialic acids, N-acetylneuraminic acid and N-glycolylneuraminic acid (Neu5Gc). Although humans cannot produce Neu5Gc, it is detected in the epithelial lining of hollow organs, endothelial lining of the vasculature, fetal tissues, and carcinomas. This unexpected expression is hypothesized to result via metabolic incorporation of Neu5Gc from mammalian foods. This accumulation has relevance for diseases associated with such nutrients, via interaction with Neu5Gc-specific antibodies. Little is known about how ingested sialic acids in general and Neu5Gc in particular are metabolized in the gastrointestinal tract. We studied the gastrointestinal and systemic fate of Neu5Gc-containing glycoproteins (Neu5Gc-glycoproteins) or free Neu5Gc in the Neu5Gc-free Cmah(-/-) mouse model. Ingested free Neu5Gc showed rapid absorption into the circulation and urinary excretion. In contrast, ingestion of Neu5Gc-glycoproteins led to Neu5Gc incorporation into the small intestinal wall, appearance in circulation at a steady-state level for several hours, and metabolic incorporation into multiple peripheral tissue glycoproteins and glycolipids, thus conclusively proving that Neu5Gc can be metabolically incorporated from food. Feeding Neu5Gc-glycoproteins but not free Neu5Gc mimics the human condition, causing tissue incorporation into human-like sites in Cmah(-/-) fetal and adult tissues, as well as developing tumors. Thus, glycoproteins containing glycosidically linked Neu5Gc are the likely dietary source for human tissue accumulation, and not the free monosaccharide. This human-like model can be used to elucidate specific mechanisms of Neu5Gc delivery from the gut to tissues, as well as general mechanisms of metabolism of ingested sialic acids.

  14. Adhesion of Porphyromonas gingivalis serotypes to pocket epithelium

    NARCIS (Netherlands)

    Dierickx, K; Pauwels, M; Laine, ML; Van Eldere, J; Cassiman, JJ; van Winkelhoff, AJ; van Steenberghe, D; Quirynen, M

    Background: Porphyromonas gingivalis, a key pathogen in periodontitis, is able to adhere to and invade the pocket epithelium. Different capsular antigens of P gingivalis have been identified (K-serotyping). These P gingivalis capsular types show differences in adhesion capacity to human cell lines

  15. Developmental origin of the posterior pigmented epithelium of iris.

    Science.gov (United States)

    Wang, Xiaobing; Xiong, Kai; Lu, Lei; Gu, Dandan; Wang, Songtao; Chen, Jing; Xiao, Honglei; Zhou, Guomin

    2015-03-01

    Iris epithelium is a double-layered pigmented cuboidal epithelium. According to the current model, the neural retina and the posterior iris pigment epithelium (IPE) are derived from the inner wall of the optic cup, while the retinal pigment epithelium (RPE) and the anterior IPE are derived from the outer wall of the optic cup during development. Our current study shows evidence, contradicting this model of fetal iris development. We demonstrate that human fetal iris expression patterns of Otx2 and Mitf transcription factors are similar, while the expressions of Otx2 and Sox2 are complementary. Furthermore, IPE and RPE exhibit identical morphologic development during the early embryonic period. Our results suggest that the outer layer of the optic cup forms two layers of the iris epithelium, and the posterior IPE is the inward-curling anterior rim of the outer layer of the optic cup. These findings provide a reasonable explanation of how IPE cells can be used as an appropriate substitute for RPE cells.

  16. Arsenic in cooked rice: Effect of chemical, enzymatic and microbial processes on bioaccessibility and speciation in the human gastrointestinal tract

    International Nuclear Information System (INIS)

    Sun Guoxin; Van de Wiele, Tom; Alava, Pradeep; Tack, Filip; Du Laing, Gijs

    2012-01-01

    Rice, used as staple food for half of the world population, can easily accumulate arsenic (As) into its grain, which often leads to As contamination. The health risk induced by presence of As in food depends on its release from the food matrix, i.e., its bioaccessibility. Using an in vitro gastrointestinal simulator, we incubated two types of cooked rice (total As: 0.389 and 0.314 mg/kg). Arsenic bioaccessibility and speciation changes were determined upon gastrointestinal digestion. Washing with deionized water and cooking did not result in changes of As speciation in the rice although the arsenic content dropped by 7.1–20.6%. Arsenic bioaccessibility of the cooked rice in the small intestine ranged between 38 and 57%. Bioaccessibility slightly increased during digestion in the simulated small intestine and decreased with time in the simulated colon. Significant speciation changes were noted in the simulated colon, with trivalent monomethylarsonate (MMA III ) becoming an important species. - Highlights: ► We studied arsenic bioaccessibility and speciation in rice during in vitro digestion. ► Bioaccessibility in cooked rice ranged between 38 and 57%. ► Bioaccessibility increased in the small intestine and dropped in the colon. ► Significant speciation changes were observed in the colon. ► Toxic trivalent monomethylarsonate (MMA III ) was produced in the colon. - Arsenic bioaccessibility and speciation changes were studied upon in vitro gastrointestinal digestion of As-polluted rice with specific attention to the role of colon micro-organisms.

  17. Reconstituted human corneal epithelium: a new alternative to the Draize eye test for the assessment of the eye irritation potential of chemicals and cosmetic products.

    Science.gov (United States)

    Doucet, O; Lanvin, M; Thillou, C; Linossier, C; Pupat, C; Merlin, B; Zastrow, L

    2006-06-01

    The aim of this study was to evaluate the interest of a new three-dimensional epithelial model cultivated from human corneal cells to replace animal testing in the assessment of eye tolerance. To this end, 65 formulated cosmetic products and 36 chemicals were tested by means of this in vitro model using a simplified toxicokinetic approach. The chemicals were selected from the ECETOC data bank and the EC/HO International validation study list. Very satisfactory results were obtained in terms of concordance with the Draize test data for the formulated cosmetic products. Moreover, the response of the corneal model appeared predictive of human ocular response clinically observed by ophthalmologists. The in vitro scores for the chemicals tested strongly correlated with their respective scores in vivo. For all the compounds tested, the response of the corneal model to irritants was similar regardless of their chemical structure, suggesting a good robustness of the prediction model proposed. We concluded that this new three-dimensional epithelial model, developed from human corneal cells, could be promising for the prediction of eye irritation induced by chemicals and complex formulated products, and that these two types of materials should be tested using a similar protocol. A simple shortening of the exposure period was required for the chemicals assumed to be more aggressively irritant to the epithelial tissues than the cosmetic formulae.

  18. Stratum corneum lipid liposome-encapsulated panomycocin: preparation, characterization, and the determination of antimycotic efficacy against Candida spp. isolated from patients with vulvovaginitis in an in vitro human vaginal epithelium tissue model.

    Science.gov (United States)

    İzgü, Fatih; Bayram, Günce; Tosun, Kübra; İzgü, Demet

    2017-01-01

    In this study, a liposomal lyophilized powder formulation of panomycocin was developed for therapeutic purposes against vulvovaginal candidiasis which affects 80% of women worldwide. Panomycocin is a potent antimycotic protein secreted by the yeast Wickerhamomyces anomalus NCYC 434. This study involved the preparation of panomycocin-loaded stratum corneum lipid liposomes (SCLLs), characterization of the SCLLs, and determination of antimycotic efficacy of the formulation against Candida albicans and Candida glabrata clinical vaginal isolates in a human vaginal epithelium tissue model. The encapsulation and loading efficiencies of SCLLs were 73% and 76.8%, respectively. In transmission electron microscopy images, the SCLLs appeared in the submicron size range. Dynamic light scattering analyses showed that the SCLLs had uniform size distribution. Zeta potential measurements revealed stable and positively charged SCLLs. In Fourier transform infrared spectroscopy analyses, no irreversible interactions between the encapsulated panomycocin and the SCLLs were detected. The SCLLs retained >98% of encapsulated panomycocin in aqueous solution up to 12 hours. The formulation was fungicidal at the same minimum fungicidal concentration values for non-formulated pure panomycocin when tested on an in vitro model of vaginal candidiasis. This is the first study in which SCLLs and a protein as an active ingredient have been utilized together in a formulation. The results obtained in this study led us to conduct further preclinical trials of this formulation for the development of an effective topical anti-candidal drug with improved safety.

  19. Competitive fitness of influenza B viruses with neuraminidase inhibitor-resistant substitutions in a coinfection model of the human airway epithelium.

    Science.gov (United States)

    Burnham, Andrew J; Armstrong, Jianling; Lowen, Anice C; Webster, Robert G; Govorkova, Elena A

    2015-04-01

    Influenza A and B viruses are human pathogens that are regarded to cause almost equally significant disease burdens. Neuraminidase (NA) inhibitors (NAIs) are the only class of drugs available to treat influenza A and B virus infections, so the development of NAI-resistant viruses with superior fitness is a public health concern. The fitness of NAI-resistant influenza B viruses has not been widely studied. Here we examined the replicative capacity and relative fitness in normal human bronchial epithelial (NHBE) cells of recombinant influenza B/Yamanashi/166/1998 viruses containing a single amino acid substitution in NA generated by reverse genetics (rg) that is associated with NAI resistance. The replication in NHBE cells of viruses with reduced inhibition by oseltamivir (recombinant virus with the E119A mutation generated by reverse genetics [rg-E119A], rg-D198E, rg-I222T, rg-H274Y, rg-N294S, and rg-R371K, N2 numbering) or zanamivir (rg-E119A and rg-R371K) failed to be inhibited by the presence of the respective NAI. In a fluorescence-based assay, detection of rg-E119A was easily masked by the presence of NAI-susceptible virus. We coinfected NHBE cells with NAI-susceptible and -resistant viruses and used next-generation deep sequencing to reveal the order of relative fitness compared to that of recombinant wild-type (WT) virus generated by reverse genetics (rg-WT): rg-H274Y > rg-WT > rg-I222T > rg-N294S > rg-D198E > rg-E119A ≫ rg-R371K. Based on the lack of attenuated replication of rg-E119A in NHBE cells in the presence of oseltamivir or zanamivir and the fitness advantage of rg-H274Y over rg-WT, we emphasize the importance of these substitutions in the NA glycoprotein. Human infections with influenza B viruses carrying the E119A or H274Y substitution could limit the therapeutic options for those infected; the emergence of such viruses should be closely monitored. Influenza B viruses are important human respiratory pathogens contributing to a significant portion

  20. Differential responses of cells from human skin keratinocyte and bovine mammary epithelium to attack by pore-forming Staphylococcus aureus alpha-toxin.

    Science.gov (United States)

    Suriyaphol, Gunnaporn; Sarikaputi, Meena; Suriyaphol, Prapat

    2009-11-01

    Human skin keratinocytes HaCat attacked by Staphylococcus aureus alpha-toxin showed a transient drop of cellular ATP levels whereas in toxin-perforated bovine mammary epithelial cells (BMEC), the ATP levels dropped more slowly. Morphologically, during the ATP level depletion, HaCat cell developed a spacious intracellular vacuole together with the transient influx of trypan blue. WST-1 signal, which tested the function of mitochondrial enzyme in viable cells, also decreased concomitantly. On the other hand, BMEC excluded trypan blue and vacuolation was not observed throughout the experiment. We conclude that mammary epithelial cells resist the toxin better than keratinocytes. This is the first report showing that alpha-toxin enhances transient membrane permeability to large molecules, temporary vacuole formation and the transient defect of mitochondrial enzyme in viable cells without cell lysis.

  1. Gastrointestinal tract

    International Nuclear Information System (INIS)

    James, R.D.; Pointon, R.C.S.

    1985-01-01

    At the time of writing, radiotherapy is of only minor use in the management of adenocarcinoma of the gastrointestinal tract, for a number of reasons. First, an exploratory laparotomy is generally needed for diagnosis, and if possible the tumour is resected or by-passed. Second, radiotherapy planning in the upper abdomen is complicated by the proximity of small bowel, kidneys, and spinal cord. Third, it has been assumed that these tumours cause death largely as a result of distant metastases, so that local radiotherapy, even if effective, would contribute little to survival. The continued interest in radiotherapy for this group of tumours arises out of the poor survival rates following surgery, which have not changed for many years, and the morbidity associated with their resection. It was hoped that the addition of cytotoxic agents to radical surgery would improve survival rates in carcinoma of the stomach and intraperitoneal colon. Despite a large number of well-organised prospective trials, using a variety of cytotoxic drugs, there is so far no evidence that the addition of chemotherapy to radical surgery improves survival for either tumour site. The authors are therefore faced with a group of tumours which are not only common, but commonly fatal and many surgeons would accept that a new approach using modern radiotherapy techniques may well be justified. There is evidence that this movement is already taking place for carcinoma of the rectum, and the indications for radiotherapy in this condition will be dealt with below. Before considering these it is worth dwelling briefly on recent changes in surgical and radiological practices which, if they fulfil expectations, might allow radiotherapy to be used for carcinoma of the colon, stomach, and pancreas as it is now used for rectal cancer

  2. Human milk probiotic Lactobacillus fermentum CECT5716 reduces the incidence of gastrointestinal and upper respiratory tract infections in infants.

    Science.gov (United States)

    Maldonado, José; Cañabate, Francisco; Sempere, Luis; Vela, Francisco; Sánchez, Ana R; Narbona, Eduardo; López-Huertas, Eduardo; Geerlings, Arjan; Valero, Antonio D; Olivares, Mónica; Lara-Villoslada, Federico

    2012-01-01

    The aim of the study was to examine the effects of a follow-on formula containing Lactobacillus fermentum CECT5716 (L. fermentum) on the incidence of infections in infants between the ages of 6 and 12 months. A randomized double-blinded controlled study including infants at the age of 6 months was conducted. Infants were assigned randomly to either follow-on formula supplemented with L. fermentum plus galactooligosaccharide (experimental group, EG), or the same formula supplemented with only galactooligosaccharide (control group, CG). The main outcome was the incidence of infections for the 6-month duration of the study. The EG showed a significant 46% reduction in the incidence rate (IR) of gastrointestinal infections (EG: 0.196 ± 0.51, CG: 0.363 ± 0.53, IR ratio 0.54, 95% confidence interval [CI] 0.307-0.950, P = 0.032), 27% reduction in the incidence of upper respiratory tract infections (EG: 0.969 ± 0.96, CG: 1.330 ± 1.23, IR ratio 0.729, 95% CI 0.46-1.38, P = 0.026), and 30% reduction in the total number of infections (EG: 1.464 ± 1.15, CG: 2.077 ± 1.59, IR ratio 0.70, 95% CI 0.46-1.38, P = 0.003), at the end of the study period compared with CG. Administration of a follow-on formula with L. fermentum CECT5716 may be useful for the prevention of community-acquired gastrointestinal and upper respiratory infections.

  3. Specificity of tumor necrosis factor toxicity for human mammary carcinomas relative to normal mammary epithelium and correlation with response to doxorubicin

    International Nuclear Information System (INIS)

    Dollbaum, C.; Creasey, A.A.; Dairkee, S.H.; Hiller, A.J.; Rudolph, A.R.; Lin, L.; Vitt, C.; Smith, H.S.

    1988-01-01

    By using a unique short-term culture system capable of growing both normal and malignant breast epithelial tissue, human recombinant tumor necrosis factor (TNF) showed preferential cytotoxicity to malignant cells as compared to the corresponding nonmalignant cells. Most of the malignant specimens were sensitive to TNF with 13 of 18 specimens showing 90% inhibition of clonal growth (ID 90 ). In contrast, all 13 nonmalignant specimens tested clustered at the resistant end of the TNF response spectrum. This differential sensitivity to TNF was seen in three cases in which malignant and nonmalignant breast epithelial tissues from the same patient were studied. To investigate the mechanism of resistance to TNF by normal cells, the presence of receptors for TNF was determined. Five of six cultures showed specific binding of 125 I-labeled TNF and there was no relationship between the degree of resistance and the degree of specific binding. Simultaneous comparison of tumor responsiveness to doxorubicin and TNF revealed a positive correlation in ID 90 values; these results may have important implications for the clinical use of TNF in cancer patients heavily pretreated with doxorubicin

  4. A unique polysaccharide purified from Hericium erinaceus mycelium prevents oxidative stress induced by H2O2 in human gastric mucosa epithelium cell.

    Science.gov (United States)

    Wang, Mingxing; Kanako, Nakajima; Zhang, Yanqiu; Xiao, Xulang; Gao, Qipin; Tetsuya, Konishi

    2017-01-01

    Hericium erinaceus (HE) has been used both as a traditional Chinese medicine and home remedy for treatment of gastric and duodenal ulcers and gastritis. EP-1, a purified polysaccharide isolated from HE mycelium, has recently been identified as the active component responsible for HE anti-gastritis activity. Because oxidative stress has been implicated as a pathogenic cause of gastritis and gastric ulcers, EP-1 antioxidant properties were systematically examined in vitro using the human gastric mucosal epithelial cell line, GES-1. Results showed that EP-1 possessed higher oxygen radical absorbance capacity (ORAC) and 2-3 times higher ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide and hydroxyl radicals than a hot water extract of commercially available HE fruiting body. A crude mycelial polysaccharide (CMPS) extract of HE, from which EP-1 was purified, showed slightly stronger radical scavenging activity and ORAC than EP-1, with the exception of DPPH-scavenging activity. Antioxidant activities of these extracts were further studied using hydrogen peroxide (H2O2)-abused GES-1 cells; EP-1 dose-dependently preserved cell viability of abused cells as assessed via MTT assay. Moreover, FACS analysis revealed that EP-1 prevented H2O2-induced apoptotic cell death by inhibiting activation of apoptotic cellular signals within mitochondria-dependent apoptotic pathways. CMPS also prevented H2O2-induced oxidative stress, but to a lesser degree than did EP-1, even though CMPS exhibited comparable or stronger in vitro antioxidant activity than did EP-1.

  5. Quantum Dot Distribution in the Olfactory Epithelium After Nasal Delivery

    Science.gov (United States)

    Garzotto, D.; De Marchis, S.

    2010-10-01

    Nanoparticles are used in a wide range of human applications from industrial to bio-medical fields. However, the unique characteristics of nanoparticles, such as the small size, large surface area per mass and high reactivity raises great concern on the adverse effects of these particles on ecological systems and human health. There are several pioneer studies reporting translocation of inhaled particulates to the brain through a potential neuronal uptake mediated by the olfactory nerve (1, 2, 3). However, no direct evidences have been presented up to now on the pathway followed by the nanoparticles from the nose to the brain. In addition to a neuronal pathway, nanoparticles could gain access to the central nervous system through extracellular pathways (perineuronal, perivascular and cerebrospinal fluid paths). In the present study we investigate the localization of intranasally delivered fluorescent nanoparticles in the olfactory epithelium. To this purpose we used quantum dots (QDs), a model of innovative fluorescent semiconductor nanocrystals commonly used in cell and animal biology (4). Intranasal treatments with QDs were performed acutely on adult CD1 mice. The olfactory epithelium was collected and analysed by confocal microscopy at different survival time after treatment. Data obtained indicate that the neuronal components of the olfactory epithelium are not preferentially involved in QDs uptake, thus suggesting nanoparticles can cross the olfactory epithelium through extracellular pathways.

  6. Assessment of the proliferative, apoptotic and cellular renovation indices of the human mammary epithelium during the follicular and luteal phases of the menstrual cycle

    International Nuclear Information System (INIS)

    Navarrete, Maria Alicia H; Maier, Carolina M; Falzoni, Roberto; Quadros, Luiz Gerk de Azevedo; Lima, Geraldo R; Baracat, Edmund C; Nazário, Afonso CP

    2005-01-01

    During the menstrual cycle, the mammary gland goes through sequential waves of proliferation and apoptosis. In mammary epithelial cells, hormonal and non-hormonal factors regulate apoptosis. To determine the cyclical effects of gonadal steroids on breast homeostasis, we evaluated the apoptotic index (AI) determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining in human mammary epithelial cells during the spontaneous menstrual cycle and correlated it with cellular proliferation as determined by the expression of Ki-67 during the same period. Normal breast tissue samples were obtained from 42 randomly selected patients in the proliferative (n = 21) and luteal (n = 21) phases. Menstrual cycle phase characterization was based on the date of the last and subsequent menses, and on progesterone serum levels obtained at the time of biopsy. The proliferation index (PI), defined as the number of Ki-67-positive nuclei per 1,000 epithelial cells, was significantly larger in the luteal phase (30.46) than in the follicular phase (13.45; P = 0.0033). The AI was defined as the number of TUNEL-positive cells per 1,000 epithelial cells. The average AI values in both phases of the menstrual cycle were not statistically significant (P = 0.21). However, the cell renewal index (CRI = PI/AI) was significantly higher in the luteal phase (P = 0.033). A significant cyclical variation of PI, AI and CRI was observed. PI and AI peaks occurred on about the 24th day of the menstrual cycle, whereas the CRI reached higher values on the 28th day. We conclude that proliferative activity is dependent mainly on hormonal fluctuations, whereas apoptotic activity is probably regulated by hormonal and non-hormonal factors

  7. The effect of culture density and proliferation rate on the expression of ouabain-sensitive Na/K ATPase pumps in cultured human retinal pigment epithelium

    International Nuclear Information System (INIS)

    Burke, J.M.; Jaffe, G.J.; Brzeski, C.M.

    1991-01-01

    The number and activity of ouabain-sensitive Na/K ATPase pumps expressed by many cell types in vitro, including human retinal pigment epithelial cells (RPE), have been shown to decline with increasing culture density. Cell proliferation also declined as cultures became dense so it was unclear if pump number was modulated by cell proliferation or culture confluency. By exposing RPE cultures to various feeding regimens, using culture medium containing or lacking serum, it was possible to produce RPE cultures with a range of culture densities and growth rates. These were analyzed for proliferative activity by quantifying [ 3 H]thymidine incorporation and for Na/K ATPase pump number by measuring specific [ 3 H]ouabain binding. The results suggest that pump number is modulated by culture density and, further, that the density-dependent regulation of pump number requires serum. Although density-dependent modulation of culture growth is also serum requiring, cell proliferation and pump number did not appear to be related; cultures of similar density which differed significantly in growth rate had similar numbers of pumps. The view that elevated numbers of pumps were not necessarily found in proliferating cells was further supported by qualitative examination of radioautographs of cells dually labeled with [ 3 H]thymidine and [ 3 H]ouabain. Cycling cells which had [ 3 H]thymidine-labeled nuclei did not have notably higher labeling with [ 3 H]ouabain. However, [ 3 H]ouabain labeling, as an indicator of pump site number and distribution, did vary among cells in an RPE population and also within individual cells. This latter observation suggests that unpolarized RPE cells in sparse cultures may have regionally different requirements for ionic regulation

  8. Sterigmatocystin-induced DNA damage triggers G2 arrest via an ATM/p53-related pathway in human gastric epithelium GES-1 cells in vitro.

    Directory of Open Access Journals (Sweden)

    Donghui Zhang

    Full Text Available Sterigmatocystin (ST, which is commonly detected in food and feed commodities, is a mutagenic and carcinogenic mycotoxin that has been recognized as a possible human carcinogen. Our previous study showed that ST can induce G2 phase arrest in GES-1 cells in vitro and that the MAPK and PI3K signaling pathways are involved in the ST-induced G2 arrest. It is now widely accepted that DNA damage plays a critical role in the regulation of cell cycle arrest and apoptosis. In response to DNA damage, a complex signaling network is activated in eukaryotic cells to trigger cell cycle arrest and facilitate DNA repair. To further explore the molecular mechanism through which ST induces G2 arrest, the current study was designed to precisely dissect the role of DNA damage and the DNA damage sensor ataxia telangiectasia-mutated (ATM/p53-dependent pathway in the ST-induced G2 arrest in GES-1 cells. Using the comet assay, we determined that ST induces DNA damage, as evidenced by the formation of DNA comet tails, in GES-1 cells. We also found that ST induces the activation of ATM and its downstream molecules, Chk2 and p53, in GES-1 cells. The ATM pharmacological inhibitor caffeine was found to effectively inhibit the activation of the ATM-dependent pathways and to rescue the ST-induced G2 arrest in GES-1 cells, which indicating its ATM-dependent characteristic. Moreover, the silencing of the p53 expression with siRNA effectively attenuated the ST-induced G2 arrest in GES-1 cells. We also found that ST induces apoptosis in GES-1 cells. Thus, our results show that the ST-induced DNA damage activates the ATM/53-dependent signaling pathway, which contributes to the induction of G2 arrest in GES-1 cells.

  9. The effect of culture density and proliferation rate on the expression of ouabain-sensitive Na/K ATPase pumps in cultured human retinal pigment epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Burke, J.M.; Jaffe, G.J.; Brzeski, C.M. (Medical College of Wisconsin, Milwaukee (USA))

    1991-06-01

    The number and activity of ouabain-sensitive Na/K ATPase pumps expressed by many cell types in vitro, including human retinal pigment epithelial cells (RPE), have been shown to decline with increasing culture density. Cell proliferation also declined as cultures became dense so it was unclear if pump number was modulated by cell proliferation or culture confluency. By exposing RPE cultures to various feeding regimens, using culture medium containing or lacking serum, it was possible to produce RPE cultures with a range of culture densities and growth rates. These were analyzed for proliferative activity by quantifying ({sup 3}H)thymidine incorporation and for Na/K ATPase pump number by measuring specific ({sup 3}H)ouabain binding. The results suggest that pump number is modulated by culture density and, further, that the density-dependent regulation of pump number requires serum. Although density-dependent modulation of culture growth is also serum requiring, cell proliferation and pump number did not appear to be related; cultures of similar density which differed significantly in growth rate had similar numbers of pumps. The view that elevated numbers of pumps were not necessarily found in proliferating cells was further supported by qualitative examination of radioautographs of cells dually labeled with ({sup 3}H)thymidine and ({sup 3}H)ouabain. Cycling cells which had ({sup 3}H)thymidine-labeled nuclei did not have notably higher labeling with ({sup 3}H)ouabain. However, ({sup 3}H)ouabain labeling, as an indicator of pump site number and distribution, did vary among cells in an RPE population and also within individual cells. This latter observation suggests that unpolarized RPE cells in sparse cultures may have regionally different requirements for ionic regulation.

  10. A unique polysaccharide purified from Hericium erinaceus mycelium prevents oxidative stress induced by H2O2 in human gastric mucosa epithelium cell.

    Directory of Open Access Journals (Sweden)

    Mingxing Wang

    Full Text Available Hericium erinaceus (HE has been used both as a traditional Chinese medicine and home remedy for treatment of gastric and duodenal ulcers and gastritis. EP-1, a purified polysaccharide isolated from HE mycelium, has recently been identified as the active component responsible for HE anti-gastritis activity. Because oxidative stress has been implicated as a pathogenic cause of gastritis and gastric ulcers, EP-1 antioxidant properties were systematically examined in vitro using the human gastric mucosal epithelial cell line, GES-1. Results showed that EP-1 possessed higher oxygen radical absorbance capacity (ORAC and 2-3 times higher ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH, superoxide and hydroxyl radicals than a hot water extract of commercially available HE fruiting body. A crude mycelial polysaccharide (CMPS extract of HE, from which EP-1 was purified, showed slightly stronger radical scavenging activity and ORAC than EP-1, with the exception of DPPH-scavenging activity. Antioxidant activities of these extracts were further studied using hydrogen peroxide (H2O2-abused GES-1 cells; EP-1 dose-dependently preserved cell viability of abused cells as assessed via MTT assay. Moreover, FACS analysis revealed that EP-1 prevented H2O2-induced apoptotic cell death by inhibiting activation of apoptotic cellular signals within mitochondria-dependent apoptotic pathways. CMPS also prevented H2O2-induced oxidative stress, but to a lesser degree than did EP-1, even though CMPS exhibited comparable or stronger in vitro antioxidant activity than did EP-1.

  11. Fetal-juvenile origins of point mutations in the adult human tracheal-bronchial epithelium: Absence of detectable effects of age, gender or smoking status

    Energy Technology Data Exchange (ETDEWEB)

    Sudo, Hiroko [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Toray Industries, Inc., New Frontiers Research Laboratories 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555 (Japan); Li-Sucholeiki, Xiao-Cheng [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Agencourt Bioscience Corp., 500 Cummings Center, Suite 2450, Beverly, MA 01915 (United States); Marcelino, Luisa A. [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Biomedical Engineering Department, Northwestern University, 633 Clark Street, Evanston, IL 60208 (United States); Gruhl, Amanda N. [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Herrero-Jimenez, Pablo [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); SLC Ontario, 690 Dorval Drive, Suite 200, Oakville, Ontario L6K 3W7 Canada (Canada); Zarbl, Helmut [UMDNJ-Robert Wood Johnson Medical School, Environmental and Occupational Health Sciences Institute, 170 Freylinghuysen Road, Room 426, Piscataway, NJ 08854 (United States); Willey, James C. [Medical College of Ohio, 3120 Glendale Avenue, Room 12, Toledo, OH 43614 (United States); Furth, Emma E. [University of Pennsylvania Medical Center, Department of Pathology, 3400 Spruce Street, 6 Founders Building, Philadelphia, PA 19104 (United States); Morgenthaler, Stephan [Institute of Applied Mathematics, Swiss Federal Institute of Technology (EPFL), SB/IMA, 1015 Lausanne (Switzerland)] (and others)

    2008-11-10

    Allele-specific mismatch amplification mutation assays (MAMA) of anatomically distinct sectors of the upper bronchial tracts of nine nonsmokers revealed many numerically dispersed clusters of the point mutations C742T, G746T, G747T of the TP53 gene, G35T of the KRAS gene and G508A of the HPRT1 gene. Assays of these five mutations in six smokers have yielded quantitatively similar results. One hundred and eighty four micro-anatomical sectors of 0.5-6 x 10{sup 6} tracheal-bronchial epithelial cells represented en toto the equivalent of approximately 1.7 human smokers' bronchial trees to the fifth bifurcation. Statistically significant mutant copy numbers above the 95% upper confidence limits of historical background controls were found in 198 of 425 sector assays. No significant differences (P = 0.1) for negative sector fractions, mutant fractions, distributions of mutant cluster size or anatomical positions were observed for smoking status, gender or age (38-76 year). Based on the modal cluster size of mitochondrial point mutants, the size of the adult bronchial epithelial maintenance turnover unit was estimated to be about 32 cells. When data from all 15 lungs were combined the log 2 of nuclear mutant cluster size plotted against log 2 of the number of clusters of a given cluster size displayed a slope of {approx}1.1 over a range of cluster sizes from {approx}2{sup 6} to 2{sup 15} mutant copies. A parsimonious interpretation of these nuclear and previously reported data for lung epithelial mitochondrial point mutant clusters is that they arose from mutations in stem cells at a high but constant rate per stem cell doubling during at least ten stem cell doublings of the later fetal-juvenile period. The upper and lower decile range of summed point mutant fractions among lungs was about 7.5-fold, suggesting an important source of stratification in the population with regard to risk of tumor initiation.

  12. Gastrointestinal helminth parasites of pet and stray dogs as a potential risk for human health in Bahir Dar town, north-western Ethiopia

    Directory of Open Access Journals (Sweden)

    Tadiwos Abere

    Full Text Available Aim: A cross-sectional study was carried out from November 2011 to April 2012 to determine the prevalence and species of gastrointestinal (GI helminth parasites in pet and stray dogs as a potential risk for human health in Bahir Dar town, northwestern Ethiopia. Materials and Methods: A total of 384 and 46 faecal samples were collected from pet and stray dogs, respectively and xamined by using standard coprologic techniques. Results: The overall prevalence of GI helminth infection in pet and stray dogs was 75.26 and 84.78%, respectively. The detected parasites with their frequencies in pet dogs were Ancylostoma caninum (78.89%, Toxocara canis (39.79%, Dipylidium caninum (29.75%, Strongyloides stercoralis (29.06%, Taeniidae (23.87% and Trichuris vulpis (7.95%. Stray dogs were found more likely to be polyparasitized and presented higher prevalence of A. caninum, T. canis, S. stercoralis, Trichuris vulpis and Taeniidae (P < 0.05 than domiciled ones. Diphyllobothrium latum was detected only in 10.25% of stray dogs. Toxocara canis and A. caninum (P < 0.05 were detected more frequently in dogs with less than 6 months of age (P <0.05 than old age dogs. The sex or breed groups didn't significantly affect the prevalence of parasites. A significant variation was recorded (P < 0.05 between different feeding systems where higher prevalence was observed in uncontrolled feeding group (82.18% compared to controlled feeding (32.08%. Conclusion: Different gastrointestinal parasites in pet and stray dogs were identified in the study area that can potentially infect humans and cause serious public-health problems. Thus, concerted efforts should therefore be made to educate dog owners to embrace modern dog disease control programs and measures have to be taken on stray dogs. [Vet World 2013; 6(7.000: 388-392

  13. Immunity to gastrointestinal nematode infections

    DEFF Research Database (Denmark)

    Sorobetea, D.; Svensson Frej, M.; Grencis, R.

    2018-01-01

    Numerous species of nematodes have evolved to inhabit the gastrointestinal tract of animals and humans, with over a billion of the world's population infected with at least one species. These large multicellular pathogens present a considerable and complex challenge to the host immune system give...

  14. LC-MS/MS Based Quantitation of ABC and SLC Transporter Proteins in Plasma Membranes of Cultured Primary Human Retinal Pigment Epithelium Cells and Immortalized ARPE19 Cell Line.

    Science.gov (United States)

    Pelkonen, Laura; Sato, Kazuki; Reinisalo, Mika; Kidron, Heidi; Tachikawa, Masanori; Watanabe, Michitoshi; Uchida, Yasuo; Urtti, Arto; Terasaki, Tetsuya

    2017-03-06

    The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier between neural retina and choroid. The RPE has several important vision supporting functions, such as transport mechanisms that may also modify pharmacokinetics in the posterior eye segment. Expression of plasma membrane transporters in the RPE cells has not been quantitated. The aim of this study was to characterize and compare transporter protein expression in the ARPE19 cell line and hfRPE (human fetal RPE) cells by using quantitative targeted absolute proteomics (QTAP). Among 41 studied transporters, 16 proteins were expressed in hfRPE and 13 in ARPE19 cells. MRP1, MRP5, GLUT1, 4F2hc, TAUT, CAT1, LAT1, and MATE1 proteins were detected in both cell lines within 4-fold differences. MPR7, OAT2 and RFC1 were detected in the hfRPE cells, but their expression levels were below the limit of quantification in ARPE19 cells. PCFT was detected in both studied cell lines, but the expression was over 4-fold higher in hfRPE cells. MCT1, MCT4, MRP4, and Na + /K + ATPase were upregulated in the ARPE19 cell line showing over 4-fold differences in the quantitative expression values. Expression levels of 25 transporters were below the limit of quantification in both cell models. In conclusion, we present the first systematic and quantitative study on transporter protein expression in the plasma membranes of ARPE19 and hfRPE cells. Overall, transporter expression in the ARPE19 and hfRPE cells correlated well and the absolute expression levels were similar, but not identical. The presented quantitative expression levels could be a useful basis for further studies on drug permeation in the outer blood-retinal barrier.

  15. Structure-based virtual screening toward the discovery of novel inhibitors for impeding the protein-protein interaction between HIV-1 integrase and human lens epithelium-derived growth factor (LEDGF/p75).

    Science.gov (United States)

    Panwar, Umesh; Singh, Sanjeev Kumar

    2017-10-23

    HIV-1 integrase is a unique promising component of the viral replication cycle, catalyzing the integration of reverse transcribed viral cDNA into the host cell genome. Generally, IN activity requires both viral as well as a cellular co-factor in the processing replication cycle. Among them, the human lens epithelium-derived growth factor (LEDGF/p75) represented as promising cellular co-factor which supports the viral replication by tethering IN to the chromatin. Due to its major importance in the early steps of HIV replication, the interaction between IN and LEDGF/p75 has become a pleasing target for anti-HIV drug discovery. The present study involves the finding of novel inhibitor based on the information of dimeric CCD of IN in complex with known inhibitor, which were carried out by applying a structure-based virtual screening concept with molecular docking. Additionally, Free binding energy, ADME properties, PAINS analysis, Density Functional Theory, and Enrichment Calculations were performed on selected compounds for getting a best lead molecule. On the basis of these analyses, the current study proposes top 3 compounds: Enamine-Z742267384, Maybridge-HTS02400, and Specs-AE-848/37125099 with acceptable pharmacological properties and enhanced binding affinity to inhibit the interaction between IN and LEDGF/p75. Furthermore, Simulation studies were carried out on these molecules to expose their dynamics behavior and stability. We expect that the findings obtained here could be future therapeutic agents and may provide an outline for the experimental studies to stimulate the innovative strategy for research community.

  16. Encapsulation of probiotic Bifidobacterium longum BIOMA 5920 with alginate-human-like collagen and evaluation of survival in simulated gastrointestinal conditions.

    Science.gov (United States)

    Su, Ran; Zhu, Xiao-Li; Fan, Dai-Di; Mi, Yu; Yang, Chan-Yuan; Jia, Xin

    2011-12-01

    Alginate (ALg)-human-like collagen (HLC) microspheres were prepared by the technology of electrostatic droplet generation in order to develop a biocompatible vehicle for probiotic bacteria. Microparticles were spherical with mean particle size of 400μm. The encapsulation efficiency (EE) of ALg-HLC microspheres could reach 92-99.2%. Water-soluble and fibrous human-like collagen is combined with sodium alginate through intermolecular hydrogen bonding and electrostatic force which were investigated by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC), thus the matrix of ALg-HLC was very stable. Bifidobacterium longum BIOMA 5920, as a kind of probiotic bacteria, was encapsulated with alginate-human-like collagen to survive and function in simulated gastrointestinal juice. Microparticles were very easy to degradation in simulated intestinal juices. After incubation in simulated gastric (pH 2.0, 2h), the encapsulated B. longum BIOMA 5920 numbers were 4.81 ± 0.38 log cfu/g. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Morphological evaluation of normal human corneal epithelium

    DEFF Research Database (Denmark)

    Ehlers, Niels; Heegaard, Steffen; Hjortdal, Jesper

    2010-01-01

    of corneas from 100 consecutively selected paraffin-embedded eyes were stained with hematoxylin-eosin and Periodic Acid-Schiff (PAS). All specimens were evaluated by light microscopy. The eyes were enucleated from patients with choroidal melanoma. Corneas were considered to be normal. RESULTS: Ninety of 100...

  18. Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells - TREAT-ME-1 - a phase I, first in human, first in class trial.

    Science.gov (United States)

    von Einem, Jobst C; Peter, Sylvia; Günther, Christine; Volk, Hans-Dieter; Grütz, Gerald; Salat, Christoph; Stoetzer, Oliver; Nelson, Peter J; Michl, Marlies; Modest, Dominik P; Holch, Julian W; Angele, Martin; Bruns, Christiane; Niess, Hanno; Heinemann, Volker

    2017-10-06

    This phase I, first in human, first in class clinical study aimed at evaluating the safety, tolerability and efficacy of treatment with genetically modified mesenchymal stromal cells (MSC) in combination with ganciclovir (GCV). MSC_apceth_101 are genetically modified autologous MSCs used as vehicles for a cell-based gene therapy in patients with advanced gastrointestinal adenocarcinoma. The study design consisted of a dose-escalation 3 + 3 design. All patients ( n = 6) were treated with up to three applications of MSC_apceth_101, followed by GCV infusions given on three consecutive days starting 48 hours after injection of MSC_apceth_101. Three of six patients received a total dose of 1.5 × 10 6 cells/kg. Two patients received three doses of 1 × 10 6 cells/kg, while one patient received only two doses of 1 × 10 6 cells/kg due to a SADR. Six patients received MSC_apceth_101. No IMP-related serious adverse events occurred. Adverse-events related to IMP-injection were increased creatinine, cough, fever, and night sweat. TNF, IL-6, IL-8, IL-10 and sE-Selectin, showed that repeated application is immunologically safe, but induces a switch of the functional properties of monocytes to an inflammatory phenotype. Treatment induced stable disease in 4/6 patients, and progressive disease in 2/6 patients. Treatment with MSC_apceth_101 in combination with GCV demonstrated acceptable safety and tolerability in patients with advanced gastrointestinal adenocarcinoma.

  19. Intragastric formation and modulation of N-nitrosodimethylamine in a dynamic in vitro gastrointestinal model under human physiological conditions

    NARCIS (Netherlands)

    Krul, C.A.M.; Zeilmaker, M.J.; Schothorst, R.C.; Havenaar, R.

    2004-01-01

    Human exposure to carcinogenic N-alkylnitrosamines can occur exogenously via food consumption or endogenously by formation of these compounds through nitrosation of amine precursors. Information on the intragastric formation of NDMA from complex mixtures of precursors and inhibitors in humans is not

  20. Production of human metabolites by gastrointestinal bacteria as a potential source of post-mortem alteration of antemortem drug/metabolite concentrations.

    Science.gov (United States)

    Martindale, Stephanie M; Powers, Robert H; Bell, Suzanne C

    2015-01-01

    Previous studies have demonstrated that bacterial species are capable of transforming complex chemical substances. Several of these species, native to the human gastrointestinal tract, are active in postmortem decomposition. They have potential to cause biotransformations affecting compound-to-metabolite ratios within the human body, especially after death. Investigation of postmortem effects could supply valuable information, especially concerning compound identification and confirmation. The purpose of this research was to investigate the effects of Escherichia coli, Bacteroides fragilis, and Clostridium perfringens on diazepam and flunitrazepam in Reinforced Clostridial Medium, and to compare bacterial biotransformation products to those of human metabolism. A decrease in diazepam concentration between pre- and post-incubation was observed for samples inoculated with Escherichia coli (14.7-20.2%) as well as Bacteroides fragilis (13.9-25.7%); however there was no corresponding increase in concentration for the monitored human metabolites. Flunitrazepam demonstrated a greater concentration loss when incubated with individual bacterial species as well as mixed culture (79.2-100.0%). Samples incubated with Bacteroides fragilis, Clostridium perfringens, and mixed culture resulted in nearly complete conversion of flunitrazepam. Increased 7-aminoflunitrazepam concentrations accounted for the majority of the conversion; however discrepancies in the mass balance of the reaction suggested the possibility of a minor metabolite that was not monitored in the current analysis. These experiments served as a pilot study and proof of concept that can be adapted and applied to a realm of possibilities. Ultimately, this methodology would be ideal to study compounds that are too toxic or lethal for animal and human metabolic investigations. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium

    Science.gov (United States)

    Walker, Nancy M.; Liu, Jinghua; Stein, Sydney R.; Stefanski, Casey D.; Strubberg, Ashlee M.

    2015-01-01

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl− and HCO3− efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3−)-loading proteins and upregulation of the basolateral membrane HCO3−-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl−/HCO3− exchange with maximized gradients, it also had increased intracellular Cl− concentration relative to wild-type. Pharmacological reduction of intracellular Cl− concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl− and HCO3− efflux, which impairs pHi regulation by Ae2. Retention of Cl− and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. PMID:26542396

  2. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium.

    Science.gov (United States)

    Walker, Nancy M; Liu, Jinghua; Stein, Sydney R; Stefanski, Casey D; Strubberg, Ashlee M; Clarke, Lane L

    2016-01-15

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl(-) and HCO3 (-) efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3 (-))-loading proteins and upregulation of the basolateral membrane HCO3 (-)-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl(-)/HCO3 (-) exchange with maximized gradients, it also had increased intracellular Cl(-) concentration relative to wild-type. Pharmacological reduction of intracellular Cl(-) concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl(-) and HCO3 (-) efflux, which impairs pHi regulation by Ae2. Retention of Cl(-) and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. Copyright © 2016 the American Physiological Society.

  3. Zinc and gastrointestinal disease

    Institute of Scientific and Technical Information of China (English)

    Sonja; Skrovanek; Katherine; DiGuilio; Robert; Bailey; William; Huntington; Ryan; Urbas; Barani; Mayilvaganan; Giancarlo; Mercogliano; James; M; Mullin

    2014-01-01

    This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases.

  4. Risk factors for gastrointestinal parasite infections of dogs living around protected areas of the Atlantic Forest: implications for human and wildlife health.

    Science.gov (United States)

    Curi, N H A; Paschoal, A M O; Massara, R L; Santos, H A; Guimarães, M P; Passamani, M; Chiarello, A G

    2017-01-01

    Despite the ubiquity of domestic dogs, their role as zoonotic reservoirs and the large number of studies concerning parasites in urban dogs, rural areas in Brazil, especially those at the wildlife-domestic animal-human interface, have received little attention from scientists and public health managers. This paper reports a cross-sectional epidemiological survey of gastrointestinal parasites of rural dogs living in farms around Atlantic Forest fragments. Through standard parasitological methods (flotation and sedimentation), 13 parasite taxa (11 helminths and two protozoans) were found in feces samples from dogs. The most prevalent were the nematode Ancylostoma (47%) followed by Toxocara (18%) and Trichuris (8%). Other less prevalent (dogs younger than one year were more likely to be infected with Toxocara, and purebred dogs with Trichuris. The number of cats in the households was positively associated with Trichuris infection, while male dogs and low body scores were associated with mixed infections. The lack of associations with dog free-ranging behavior and access to forest or villages indicates that infections are mostly acquired around the households. The results highlight the risk of zoonotic and wildlife parasite infections from dogs and the need for monitoring and controlling parasites of domestic animals in human-wildlife interface areas.

  5. Hydrolysed fumonisin B1 and N-(deoxy-D-fructos-1-yl)-fumonisin B1: stability and catabolic fate under simulated human gastrointestinal conditions.

    Science.gov (United States)

    Cirlini, Martina; Hahn, Irene; Varga, Elisabeth; Dall'Asta, Margherita; Falavigna, Claudia; Calani, Luca; Berthiller, Franz; Del Rio, Daniele; Dall'Asta, Chiara

    2015-02-01

    Food processing may induce thermal degradation of fumonisins in corn via Maillard-type reactions, or alkaline hydrolysis via loss of the two tricarballylic acid moieties. In the former case, N-(1-deoxy-D-fructos-1-yl)-fumonisin B(1) (NDF) can be formed, while the latter derivative is called hydrolysed fumonisin B(1) (HFB(1)). The aim of this study was to deepen the knowledge about the gastrointestinal stability of HFB(1) and NDF in humans. Due to the lack of standard, NDF was chemically synthesised and cleaned up in high purity to be used for further experiments. While NDF is already partially cleaved (about 41%) during simulated digestion, it remained rather stable towards human colon microflora. In contrast to this, HFB(1) is partially metabolised by the colon microflora to unknown compounds after 24 h of fermentation, as seen by a loss of about 22%. Concluding, the cleavage of NDF during digestion as well as the likely metabolisation of HFB(1) emphasise the need for animal trials to ascertain their toxicity in vivo.

  6. Investigation of Genipin Cross-Linked Microcapsule for Oral Delivery of Live Bacterial Cells and Other Biotherapeutics: Preparation and In Vitro Analysis in Simulated Human Gastrointestinal Model

    Directory of Open Access Journals (Sweden)

    Hongmei Chen

    2010-01-01

    Full Text Available Oral therapy utilizing engineered microorganisms has shown promise in the treatment of many diseases. By microencapsulation, viable cells can overcome the harsh gastrointestinal (GI environment and secrete needed therapeutics into the gut. These engineered cells should be encased without escaping into the GI tract for safety concerns, thus robust microcapsule membrane is requisite. This paper examined the GI performance of a novel microcapsule membrane using a dynamic simulated human GI model. Results showed that the genipin cross-linked alginate-chitosan (GCAC microcapsules possessed strong resistance to structural disintegration in the simulated GI environment. Leakage of encapsulated high molecular weight dextran, a model material to be protected during the simulated GI transit, was negligible over 72 h of exposure, in contrast to considerable leakage of dextran from the non-cross-linked counterparts. These microcapsules did not alter the microflora and enzymatic activities in the simulated human colonic media. This study suggested the potential of the GCAC microcapsules for oral delivery of live microorganisms and other biotherapeutics.

  7. The use of double-balloon enteroscopy in retrieving mucosal biopsies from the entire human gastrointestinal tract

    DEFF Research Database (Denmark)

    Rhee, Nicolai Alexander; Vilmann, Peter; Hassan, Hazem

    2014-01-01

    OBJECTIVE: The aim of this explorative study was to evaluate double-balloon enteroscopy (DBE) as a new tool for collecting mucosal biopsies from well-defined parts of the entire small and large bowel in patients with type 2 diabetes and in matched healthy subjects. MATERIAL AND METHODS: Twelve su...... possibility to access hitherto unexplored human anatomy and physiology....

  8. Mucosal prevalence and interactions with the epithelium indicate commensalism of Sutterella spp.

    Directory of Open Access Journals (Sweden)

    Kaisa Hiippala

    2016-10-01

    Full Text Available Sutterella species have been frequently associated with human diseases, such as autism, Down syndrome and inflammatory bowel disease (IBD, but the impact of these bacteria on health still remains unclear. Especially the interactions of Sutterella spp. with the host are largely unknown, despite of the species being highly prevalent. In this study, we addressed the interaction of three known species of Sutterella with the intestinal epithelium and examined their adhesion properties, the effect on intestinal barrier function and the pro-inflammatory capacity in vitro. We also studied the relative abundance and prevalence of the genus Sutterella and S. wadsworthensis in intestinal biopsies of healthy individuals and patients with celiac disease (CeD or IBD. Our results show that Sutterella spp. are abundant in the duodenum of healthy adults with a decreasing gradient towards the colon. No difference was detected in the prevalence of Sutterella between the pediatric IBD or CeD patients and the healthy controls. Sutterella parvirubra adhered better than the two other Sutterella spp. to differentiated Caco-2 cells and was capable of decreasing the adherence of S. wadsworthensis, which preferably bound to mucus and human extracellular matrix (ECM proteins. Furthermore, only S. wadsworthensis induced an interleukin-8 (IL-8 production in enterocytes, which could be due to different lipopolysaccharide (LPS structures between the species. However, its pro-inflammatory activity was modest as compared to non-pathogenic Escherichia coli. Sutterella spp. had no effect on the enterocyte monolayer integrity in vitro. Our findings indicate that the members of genus Sutterella are widely prevalent commensals with mild pro-inflammatory capacity in the human gastrointestinal tract and do not contribute significantly to the disrupted epithelial homeostasis associated with microbiota dysbiosis and increase of Proteobacteria. The ability of Sutterella spp. to adhere to

  9. Gastrointestinal Simulation Model TWIN-SHIME Shows Differences between Human Urolithin-Metabotypes in Gut Microbiota Composition, Pomegranate Polyphenol Metabolism, and Transport along the Intestinal Tract.

    Science.gov (United States)

    García-Villalba, Rocío; Vissenaekens, Hanne; Pitart, Judit; Romo-Vaquero, María; Espín, Juan C; Grootaert, Charlotte; Selma, María V; Raes, Katleen; Smagghe, Guy; Possemiers, Sam; Van Camp, John; Tomas-Barberan, Francisco A

    2017-07-12

    A TWIN-SHIME system was used to compare the metabolism of pomegranate polyphenols by the gut microbiota from two individuals with different urolithin metabotypes. Gut microbiota, ellagitannin metabolism, short-chain fatty acids (SCFA), transport of metabolites, and phase II metabolism using Caco-2 cells were explored. The simulation reproduced the in vivo metabolic profiles for each metabotype. The study shows for the first time that microbial composition, metabolism of ellagitannins, and SCFA differ between metabotypes and along the large intestine. The assay also showed that pomegranate phenolics preserved intestinal cell integrity. Pomegranate polyphenols enhanced urolithin and propionate production, as well as Akkermansia and Gordonibacter prevalence with the highest effect in the descending colon. The system provides an insight into the mechanisms of pomegranate polyphenol gut microbiota metabolism and absorption through intestinal cells. The results obtained by the combined SHIME/Caco-2 cell system are consistent with previous human and animal studies and show that although urolithin metabolites are present along the gastrointestinal tract due to enterohepatic circulation, they are predominantly produced in the distal colon region.

  10. The junctional epithelium originates from the odontogenic epithelium of an erupted tooth.

    Science.gov (United States)

    Yajima-Himuro, Sara; Oshima, Masamitsu; Yamamoto, Gou; Ogawa, Miho; Furuya, Madoka; Tanaka, Junichi; Nishii, Kousuke; Mishima, Kenji; Tachikawa, Tetsuhiko; Tsuji, Takashi; Yamamoto, Matsuo

    2014-05-02

    The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period.

  11. Development and application of an in vitro methodology to determine the transit tolerance of potentially probiotic Lactobacillus and Bifidobacterium species in the upper human gastrointestinal tract.

    Science.gov (United States)

    Charteris, W P; Kelly, P M; Morelli, L; Collins, J K

    1998-05-01

    An in vitro methodology which mimics in vivo human upper gastrointestinal transit was developed. The transit tolerance of potentially probiotic Lactobacillus and Bifidobacterium species was determined by exposing washed cell suspensions at 37 degrees C to a simulated gastric juice (pH 2.0), containing pepsin (0.3% w/v) and sodium chloride (0.5% w/v), and a simulated small intestinal juice (pH 8.0), containing pancreatin USP (1 g l-1) and sodium chloride (5 g l-1), and monitoring changes in total viable count periodically. The methodology was also employed to determine the effect of adding milk proteins (1 g l-1), hog gastric mucin (1 g l-1) and soyabean trypsinchymotrypsin inhibitor [SBTCI] (1 g l-1) on transit tolerance. The majority (14 of 15) of isolates lost > 90% viability during simulated gastric transit. Only one isolate, Lactobacillus fermentum KLD, was considered intrinsically resistant. The addition of milk proteins, singly and in combination, generally improved gastric transit tolerance. In this regard, two isolates, Lact. casei 212.3 and Bifidobacterium infantis 25962, exhibited 100% gastric transit tolerance in the presence of milk proteins. In general, the addition of hog gastric mucin did not influence simulated gastric transit tolerance of lactobacilli but tended to increase that of bifidobacteria. However, it increased that of Lact. casei 242 and Lact. salivarius 43338 but diminished that of B. bifidum 2715 and B. animalis Bo. Selected bile salts-resistant isolates were intrinsically tolerant to simulated small intestinal transit. Only Lact. casei F19 and B. adolescentis 15703T showed significant reduction in viability after 240 min. In general, the addition of milk proteins and SBTCI did not affect simulated small intestinal transit tolerance. However, they significantly improved the intrinsic resistance of Lact. casei F19 but diminished that of B. breve 15700T. It is concluded that, whereas the majority of bile salts-resistant lactobacilli and

  12. Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements

    Directory of Open Access Journals (Sweden)

    Levitt DG

    2016-07-01

    Full Text Available David G Levitt,1,* Michael D Levitt2,* 1Department of Integrative Biology and Physiology, University of Minnesota, 2Research Service, Veterans Affairs Medical Center, Minneapolis, MN, USA *These authors contributed equally to this work Abstract: Serum albumin concentration (CP is a remarkably strong prognostic indicator of morbidity and mortality in both sick and seemingly healthy subjects. Surprisingly, the specifics of the pathophysiology underlying the relationship between CP and ill-health are poorly understood. This review provides a summary that is not previously available in the literature, concerning how synthesis, catabolism, and renal and gastrointestinal clearance of albumin interact to bring about albumin homeostasis, with a focus on the clinical factors that influence this homeostasis. In normal humans, the albumin turnover time of about 25 days reflects a liver albumin synthesis rate of about 10.5 g/day balanced by renal (≈6%, gastrointestinal (≈10%, and catabolic (≈84% clearances. The acute development of hypoalbuminemia with sepsis or trauma results from increased albumin capillary permeability leading to redistribution of albumin from the vascular to interstitial space. The best understood mechanism of chronic hypoalbuminemia is the decreased albumin synthesis observed in liver disease. Decreased albumin production also accounts for hypoalbuminemia observed with a low-protein and normal caloric diet. However, a calorie- and protein-deficient diet does not reduce albumin synthesis and is not associated with hypoalbuminemia, and CP is not a useful marker of malnutrition. In most disease states other than liver disease, albumin synthesis is normal or increased, and hypoalbuminemia reflects an enhanced rate of albumin turnover resulting either from an increased rate of catabolism (a poorly understood phenomenon or enhanced loss of albumin into the urine (nephrosis or intestine (protein-losing enteropathy. The latter may occur

  13. Transport across the choroid plexus epithelium

    DEFF Research Database (Denmark)

    Praetorius, Jeppe; Damkier, Helle Hasager

    2017-01-01

    The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus...... is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature......, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1) the choroid plexus epithelium as the source of mediators necessary for central nervous system...

  14. Human gastrointestinal tract resistance of Lactobacillus strains isolated from infant faecesResistência ao trato gastrointestinal humano de linhagens de Lactobacillus isoladas de fezes de crianças

    Directory of Open Access Journals (Sweden)

    Sandra Garcia

    2011-08-01

    Full Text Available The probiotic bacteria survival during the gastrointestinal transit is primordial, and implies in the ability of microorganisms to survive at the stomach acidity and bile, so they can exert their beneficial effects on the host. The aim of this study was to evaluate, “in vitro”, Lactobacillus strains originated from one year old children fecal material in the selection of probiotic microorganisms. Two commercial strains, L. casei (Lc 01TM and L. acidophilus (La-05 TM were used as controls. The first screening resulted in 75 colonies and they were isolated from six samples faeces. Isolates were Gram positive, mostly rod shaped (cocobacilli, long and thin rods and rarely cocci. They were submitted to catalase test and evaluated for the presence of spores, resulting in 30 pre-selected strains. Among those strains, eight strains: L4, L5, L12, L19, L20, L22, L23, L24 were the most resistant to Oxgall (bile salts concentration (0.3 w/v. These eight strains were also resistant to acid conditions (pH 3.0 and all strains were able to grow in the presence of 0.3 w/v of phenol. The results of treatments were compared to the Neuman Keuls Student test at 5% of probability, with regression analyses made at different times for tolerance to intestinal conditions. The results demonstrated that all these strains were able to survive under gastrointestinal stress condition, indicating potential use as probiotics. The high survival rate of probiotic strains, in conditions that simulate the gastrointestinal transit, is strain dependent and thus, a proper selection of strains in the development of dairy probiotic products is vital.

  15. Intestinal epithelium in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet

    2014-01-01

    The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs) that are crucial in maintaining intestinal...... of inflammatory bowel disease (IBD). Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets....

  16. Lesion of the olfactory epithelium accelerates prion neuroinvasion and disease onset when prion replication is restricted to neurons.

    Directory of Open Access Journals (Sweden)

    Jenna Crowell

    Full Text Available Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain.

  17. Lesion of the Olfactory Epithelium Accelerates Prion Neuroinvasion and Disease Onset when Prion Replication Is Restricted to Neurons

    Science.gov (United States)

    Crowell, Jenna; Wiley, James A.; Bessen, Richard A.

    2015-01-01

    Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain. PMID:25822718

  18. Risk factors for gastrointestinal parasite infections of dogs living around protected areas of the Atlantic Forest: implications for human and wildlife health

    Directory of Open Access Journals (Sweden)

    N. H. A. Curi

    Full Text Available Abstract Despite the ubiquity of domestic dogs, their role as zoonotic reservoirs and the large number of studies concerning parasites in urban dogs, rural areas in Brazil, especially those at the wildlife-domestic animal-human interface, have received little attention from scientists and public health managers. This paper reports a cross-sectional epidemiological survey of gastrointestinal parasites of rural dogs living in farms around Atlantic Forest fragments. Through standard parasitological methods (flotation and sedimentation, 13 parasite taxa (11 helminths and two protozoans were found in feces samples from dogs. The most prevalent were the nematode Ancylostoma (47% followed by Toxocara (18% and Trichuris (8%. Other less prevalent (<2% parasites found were Capillaria, Ascaridia, Spirocerca, Taeniidae, Acantocephala, Ascaris, Dipylidium caninum, Toxascaris, and the protozoans Cystoisospora and Eimeria. Mixed infections were found in 36% of samples, mostly by Ancylostoma and Toxocara. Previous deworming had no association with infections, meaning that this preventive measure is being incorrectly performed by owners. Regarding risk factors, dogs younger than one year were more likely to be infected with Toxocara, and purebred dogs with Trichuris. The number of cats in the households was positively associated with Trichuris infection, while male dogs and low body scores were associated with mixed infections. The lack of associations with dog free-ranging behavior and access to forest or villages indicates that infections are mostly acquired around the households. The results highlight the risk of zoonotic and wildlife parasite infections from dogs and the need for monitoring and controlling parasites of domestic animals in human-wildlife interface areas.

  19. Low Buffer Capacity and Alternating Motility along the Human Gastrointestinal Tract: Implications for in Vivo Dissolution and Absorption of Ionizable Drugs.

    Science.gov (United States)

    Hens, Bart; Tsume, Yasuhiro; Bermejo, Marival; Paixao, Paulo; Koenigsknecht, Mark J; Baker, Jason R; Hasler, William L; Lionberger, Robert; Fan, Jianghong; Dickens, Joseph; Shedden, Kerby; Wen, Bo; Wysocki, Jeffrey; Loebenberg, Raimar; Lee, Allen; Frances, Ann; Amidon, Greg; Yu, Alex; Benninghoff, Gail; Salehi, Niloufar; Talattof, Arjang; Sun, Duxin; Amidon, Gordon L

    2017-12-04

    In this study, we determined the pH and buffer capacity of human gastrointestinal (GI) fluids (aspirated from the stomach, duodenum, proximal jejunum, and mid/distal jejunum) as a function of time, from 37 healthy subjects after oral administration of an 800 mg immediate-release tablet of ibuprofen (reference listed drug; RLD) under typical prescribed bioequivalence (BE) study protocol conditions in both fasted and fed states (simulated by ingestion of a liquid meal). Simultaneously, motility was continuously monitored using water-perfused manometry. The time to appearance of phase III contractions (i.e., housekeeper wave) was monitored following administration of the ibuprofen tablet. Our results clearly demonstrated the dynamic change in pH as a function of time and, most significantly, the extremely low buffer capacity along the GI tract. The buffer capacity on average was 2.26 μmol/mL/ΔpH in fasted state (range: 0.26 and 6.32 μmol/mL/ΔpH) and 2.66 μmol/mL/ΔpH in fed state (range: 0.78 and 5.98 μmol/mL/ΔpH) throughout the entire upper GI tract (stomach, duodenum, and proximal and mid/distal jejunum). The implication of this very low buffer capacity of the human GI tract is profound for the oral delivery of both acidic and basic active pharmaceutical ingredients (APIs). An in vivo predictive dissolution method would require not only a bicarbonate buffer but also, more significantly, a low buffer capacity of dissolution media to reflect in vivo dissolution conditions.

  20. Nonvariceal upper gastrointestinal bleeding

    International Nuclear Information System (INIS)

    Burke, Stephen J.; Weldon, Derik; Sun, Shiliang; Golzarian, Jafar

    2007-01-01

    Nonvariceal upper gastrointestinal bleeding (NUGB) remains a major medical problem even after advances in medical therapy with gastric acid suppression and cyclooxygenase (COX-2) inhibitors. Although the incidence of upper gastrointestinal bleeding presenting to the emergency room has slightly decreased, similar decreases in overall mortality and rebleeding rate have not been experienced over the last few decades. Many causes of upper gastrointestinal bleeding have been identified and will be reviewed. Endoscopic, radiographic and angiographic modalities continue to form the basis of the diagnosis of upper gastrointestinal bleeding with new research in the field of CT angiography to diagnose gastrointestinal bleeding. Endoscopic and angiographic treatment modalities will be highlighted, emphasizing a multi-modality treatment plan for upper gastrointestinal bleeding. (orig.)

  1. Nonvariceal upper gastrointestinal bleeding

    Energy Technology Data Exchange (ETDEWEB)

    Burke, Stephen J.; Weldon, Derik; Sun, Shiliang [University of Iowa, Department of Radiology, Iowa, IA (United States); Golzarian, Jafar [University of Iowa, Department of Radiology, Iowa, IA (United States); University of Iowa, Department of Radiology, Carver College of Medicine, Iowa, IA (United States)

    2007-07-15

    Nonvariceal upper gastrointestinal bleeding (NUGB) remains a major medical problem even after advances in medical therapy with gastric acid suppression and cyclooxygenase (COX-2) inhibitors. Although the incidence of upper gastrointestinal bleeding presenting to the emergency room has slightly decreased, similar decreases in overall mortality and rebleeding rate have not been experienced over the last few decades. Many causes of upper gastrointestinal bleeding have been identified and will be reviewed. Endoscopic, radiographic and angiographic modalities continue to form the basis of the diagnosis of upper gastrointestinal bleeding with new research in the field of CT angiography to diagnose gastrointestinal bleeding. Endoscopic and angiographic treatment modalities will be highlighted, emphasizing a multi-modality treatment plan for upper gastrointestinal bleeding. (orig.)

  2. Gastrointestinal Epithelial Organoid Cultures from Postsurgical Tissues.

    Science.gov (United States)

    Hahn, Soojung; Yoo, Jongman

    2017-08-17

    An organoid is a cellular structure three-dimensionally (3D) cultured from self-organizing stem cells in vitro, which has a cell population, architectures, and organ specific functions like the originating organs. Recent advances in the 3D culture of isolated intestinal crypts or gastric glands have enabled the generation of human gastrointestinal epithelial organoids. Gastrointestinal organoids recapitulate the human in vivo physiology because of all the intestinal epithelial cell types that differentiated and proliferated from tissue resident stem cells. Thus far, gastrointestinal organoids have been extensively used for generating gastrointestinal disease models. This protocol describes the method of isolating a gland or crypt using stomach or colon tissue after surgery and establishing them into gastroids or colonoids.

  3. Shigella infection of intestinal epithelium and circumvention of the host innate defense system.

    Science.gov (United States)

    Ashida, Hiroshi; Ogawa, Michinaga; Mimuro, Hitomi; Sasakawa, Chihiro

    2009-01-01

    Shigella, Gram-negative bacteria closely related to Escherichia coli, are highly adapted human pathogens that cause bacillary dysentery. Although Shigella have neither adherence factors nor flagella required for attaching or accessing the intestinal epithelium, Shigella are capable of colonizing the intestinal epithelium by exploiting epithelial-cell functions and circumventing the host innate immune response. During Shigella infection, they deliver many numbers of effectors through the type III secretion system into the surrounding space and directly into the host-cell cytoplasm. The effectors play pivotal roles from the onset of bacterial infection through to the establishment of the colonization of the intestinal epithelium, such as bacterial invasion, intracellular survival, subversion of the host immune defense response, and maintenance of the infectious foothold. These examples suggest that Shigella have evolved highly sophisticated infectious and intracellular strategies to establish replicative niches in the intestinal epithelium.

  4. E3B1/ABI-1 Isoforms Are Down-Regulated in Cancers of Human Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Rafia A. Baba

    2012-01-01

    Full Text Available The expression of E3B1/ABI-1 protein and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors. In this study, we examined the expression pattern of E3B1/ABI-1 protein in histologically confirmed cases of esophageal (squamous cell carcinoma and adenocarcinoma, gastro-esophageal junction, colorectal cancers and corresponding normal tissues freshly resected from a cohort of 135 patients, by Western Blotting and Immunofluorescence Staining. The protein is present in its phosphorylated form in cells and tissues. Depending on the extent of phosphorylation it is either present in hyper-phosphorylated (M. Wt. 72 kDa form or in hypo-phosphorylated form (M. Wt. 68 kDa and 65 kDa. A thorough analysis revealed that expression of E3B1/ABI-1 protein is significantly decreased in esophageal, gastro-esophageal junction and colorectal carcinomas irrespective of age, gender, dietary and smoking habits of the patients. The decrease in expression of E3B1/ABI-1 was consistently observed for all the three isoforms. However, the decrease in the expression of isoforms varied with different forms of cancers. Down-regulation of E3B1/ABI-1 expression in human carcinomas may play a critical role in tumor progression and in determining disease prognosis.

  5. Transferability of a tetracycline resistance gene from probiotic Lactobacillus reuteri to bacteria in the gastrointestinal tract of humans.

    Science.gov (United States)

    Egervärn, Maria; Lindmark, Hans; Olsson, Johan; Roos, Stefan

    2010-02-01

    The potential of Lactobacillus reuteri as a donor of antibiotic resistance genes in the human gut was investigated by studying the transferability of the tetracycline resistance gene tet(W) to faecal enterococci, bifidobacteria and lactobacilli. In a double-blind clinical study, seven subjects consumed L. reuteri ATCC 55730 harbouring a plasmid-encoded tet(W) gene (tet(W)-reuteri) and an equal number of subjects consumed L. reuteri DSM 17938 derived from the ATCC 55730 strain by the removal of two plasmids, one of which contained the tet(W) gene. Faecal samples were collected before, during and after ingestion of 5 x 10(8) CFU of L. reuteri per day for 14 days. Both L. reuteri strains were detectable at similar levels in faeces after 14 days of intake but neither was detected after a two-week wash-out period. After enrichment and isolation of tetracycline resistant enterococci, bifidobacteria and lactobacilli from each faecal sample, DNA was extracted and analysed for presence of tet(W)-reuteri using a real-time PCR allelic discrimination method developed in this study. No tet(W)-reuteri signal was produced from any of the DNA samples and thus gene transfer to enterococci, bifidobacteria and lactobacilli during intestinal passage of the probiotic strain was non-detectable under the conditions tested, although transfer at low frequencies or to the remaining faecal bacterial population cannot be excluded.

  6. Gastrointestinal nuclear imaging

    International Nuclear Information System (INIS)

    Anon.

    1988-01-01

    This book contains paper grouped under the headings of: salivary scintigraphy, abscess detection with radionuclides; pediatric gastroenterology; liver spleen, and miscellaneous GI studies: gastrointestinal

  7. Gastrointestinal expression and partial cDNA cloning of murine Muc2

    NARCIS (Netherlands)

    van Klinken, B. J.; Einerhand, A. W.; Duits, L. A.; Makkink, M. K.; Tytgat, K. M.; Renes, I. B.; Verburg, M.; Büller, H. A.; Dekker, J.

    1999-01-01

    To help us investigate the role of mucin in the protection of the colonic epithelium in the mouse, we aimed to identify the murine colonic mucin (MCM) and its encoding gene. We isolated MCM, raised an anti-MCM antiserum, and studied the biosynthesis of MCM in the gastrointestinal tract. Isolated MCM

  8. Frequent detection of human adenovirus from the lower gastrointestinal tract in men who have sex with men.

    Directory of Open Access Journals (Sweden)

    Marcel E Curlin

    2010-06-01

    Full Text Available The association between baseline seropositivity to human adenovirus (HAdV type 5 and increased HIV acquisition in the Step HIV Vaccine Study has raised questions concerning frequency of acquired and/or persistent Adenovirus infections among adults at high risk of HIV-1 infection.To evaluate the frequency and pattern of HAdV shedding from the lower GI tract, we retrospectively tested rectal swabs for HAdVs in a cohort of 20 HSV-2 positive HIV-positive Peruvian men who have sex with men (MSM undergoing rectal swabbing three times/week for 18 consecutive weeks, in a prospective study of HSV-2 suppression in HIV infection. Viral DNA was extracted and amplified using a sensitive multiplex PCR assay that detects all currently recognized HAdV types. Molecular typing of viruses was performed on selected samples by hexon gene sequencing. Baseline neutralizing antibody titers to HAdVs -5, -26, -35 and -48 were also assessed.15/20 individuals had HAdV detected during follow up. The median frequency of HAdV detection was 30% of samples (range 2.0% to 64.7%. HAdV shedding typically occurred on consecutive days in clustered episodes lasting a median of 4 days (range 1 to 9 days separated by periods without shedding, suggesting frequent new infections or reactivation of latent infections over time. 8 of the 15 shedders had more than one type detected in follow-up. 20 HAdV types from species B, C, and D were identified, including HAdV-5, -26 and -48, HAdV types under development as potential vaccine candidates. 14/20 subjects were seropositive for HAdV-5; 15/20 for HAdV-26; 3/20 for HAdV-35; and 2/20 for HAdV-48. HAdV shedding did not correlate with CD4 count, plasma HIV-1 viral load, or titers to HAdV-5 or HAdV-35. The sole individual with HAdV-5 shedding was HAdV-5 seropositive.HAdV shedding was highly prevalent and diverse, including types presently under consideration as HIV vaccine vectors. Subclinical HAdV infection of the GI tract is common among MSM in

  9. Measurement of the thickness of the bronchial epithelium

    International Nuclear Information System (INIS)

    Bowden, D.H.; Baldwin, F.

    1989-02-01

    Cancer of the lung in uranium miners is thought to be related to the inhalation of gaseous radon daughters which become attached to molecules of water vapour or to dust particles. Since, the depth of tissue penetration by alpha particles is short, the thickness of the epithelium that lines the bronchial tree may be a critical factor in the development of cancers at specific sites in the lung. The objectives of the present study were: 1) to measure the thickness of human bronchial epithelium; 2) to determine the distribution and depth of the nuclei of basal cells in the bronchial epithelium; and 3) to compare these parameters in groups of smokers and non-smokers. Twenty-nine surgically removed specimens of the lung were examined (26 smokers, 3 non-smokers). The specimens were fixed and prepared for examination by light and electron microscopy. Blocks of tissue were oriented so that the maximum number of bronchi were cut in cross-section; measurements included bronchi of all sizes from bronchial generations (1≥ 9.01 mm) diameter to the smallest bronchioles, generations 7 - 16 (0.26 - 2.0 mm). Comparison of measurements in smokers and non-smokers show no significant differences, so that the 29 cases are considered to represent a homogeneous group. With progressive divisions of the bronchi, the epithelium decreases in thickness. Of more importance are the figures relating to the distance from the cell surface to the underlying nucleus. Here too, with the exception of goblet cells, the measurements are significantly smaller in generations 7 - 16 than in generation 1

  10. Gastrointestinal polyposis in Cowden disease

    International Nuclear Information System (INIS)

    Kullnig, P.; Steiner, H.; Porsch, G.; Smolle, J.

    1987-01-01

    A case of Cowden disease (multiple hamartoma syndrome) with marked gastrointestinal polyposis is presented. The differential diagnosis of gastrointestinal polyposis syndromes is discussed. (orig.) [de

  11. The gastrointestinal-brain axis in humans as an evolutionary advance of the root-leaf axis in plants: A hypothesis linking quantum effects of light on serotonin and auxin.

    Science.gov (United States)

    Tonello, Lucio; Gashi, Bekim; Scuotto, Alessandro; Cappello, Glenda; Cocchi, Massimo; Gabrielli, Fabio; Tuszynski, Jack A

    2018-01-01

    Living organisms tend to find viable strategies under ambient conditions that optimize their search for, and utilization of, life-sustaining resources. For plants, a leading role in this process is performed by auxin, a plant hormone that drives morphological development, dynamics, and movement to optimize the absorption of light (through branches and leaves) and chemical "food" (through roots). Similarly to auxin in plants, serotonin seems to play an important role in higher animals, especially humans. Here, it is proposed that morphological and functional similarities between (i) plant leaves and the animal/human brain and (ii) plant roots and the animal/human gastro-intestinal tract have general features in common. Plants interact with light and use it for biological energy, whereas, neurons in the central nervous system seem to interact with bio-photons and use them for proper brain function. Further, as auxin drives roots "arborescence" within the soil, similarly serotonin seems to facilitate enteric nervous system connectivity within the human gastro-intestinal tract. This auxin/serotonin parallel suggests the root-branches axis in plants may be an evolutionary precursor to the gastro-intestinal-brain axis in humans. Finally, we hypothesize that light might be an important factor, both in gastro-intestinal dynamics and brain function. Such a comparison may indicate a key role for the interaction of light and serotonin in neuronal physiology (possibly in both the central nervous system and the enteric nervous system), and according to recent work, mind and consciousness.

  12. A Method for Quantification of Epithelium Colonization Capacity by Pathogenic Bacteria

    Directory of Open Access Journals (Sweden)

    Rune M. Pedersen

    2018-02-01

    Full Text Available Most bacterial infections initiate at the mucosal epithelium lining the gastrointestinal, respiratory, and urogenital tracts. At these sites, bacterial pathogens must adhere and increase in numbers to effectively breach the outer barrier and invade the host. If the bacterium succeeds in reaching the bloodstream, effective dissemination again requires that bacteria in the blood, reestablish contact to distant endothelium sites and form secondary site foci. The infectious potential of bacteria is therefore closely linked to their ability to adhere to, colonize, and invade epithelial and endothelial surfaces. Measurement of bacterial adhesion to epithelial cells is therefore standard procedure in studies of bacterial virulence. Traditionally, such measurements have been conducted with microtiter plate cell cultures to which bacteria are added, followed by washing procedures and final quantification of retained bacteria by agar plating. This approach is fast and straightforward, but yields only a rough estimate of the adhesive properties of the bacteria upon contact, and little information on the ability of the bacterium to colonize these surfaces under relevant physiological conditions. Here, we present a method in which epithelia/endothelia are simulated by flow chamber-grown human cell layers, and infection is induced by seeding of pathogenic bacteria on these surfaces under conditions that simulate the physiological microenvironment. Quantification of bacterial adhesion and colonization of the cell layers is then performed by in situ time-lapse fluorescence microscopy and automatic detection of bacterial surface coverage. The method is demonstrated in three different infection models, simulating Staphylococcus aureus endothelial infection and Escherichia coli intestinal- and uroepithelial infection. The approach yields valuable information on the fitness of the bacterium to successfully adhere to and colonize epithelial surfaces and can be used

  13. deltaNp63 has a role in maintaining epithelial integrity in airway epithelium.

    Science.gov (United States)

    Arason, Ari Jon; Jonsdottir, Hulda R; Halldorsson, Skarphedinn; Benediktsdottir, Berglind Eva; Bergthorsson, Jon Thor; Ingthorsson, Saevar; Baldursson, Olafur; Sinha, Satrajit; Gudjonsson, Thorarinn; Magnusson, Magnus K

    2014-01-01

    The upper airways are lined with a pseudostratified bronchial epithelium that forms a barrier against unwanted substances in breathing air. The transcription factor p63, which is important for stratification of skin epithelium, has been shown to be expressed in basal cells of the lungs and its ΔN isoform is recognized as a key player in squamous cell lung cancer. However, the role of p63 in formation and maintenance of bronchial epithelia is largely unknown. The objective of the current study was to determine the expression pattern of the ΔN and TA isoforms of p63 and the role of p63 in the development and maintenance of pseudostratified lung epithelium in situ and in culture. We used a human bronchial epithelial cell line with basal cell characteristics (VA10) to model bronchial epithelium in an air-liquid interface culture (ALI) and performed a lentiviral-based silencing of p63 to characterize the functional and phenotypic consequences of p63 loss. We demonstrate that ΔNp63 is the major isoform in the human lung and its expression was exclusively found in the basal cells lining the basement membrane of the bronchial epithelium. Knockdown of p63 affected proliferation and migration of VA10 cells and facilitated cellular senescence. Expression of p63 is critical for epithelial repair as demonstrated by wound healing assays. Importantly, generation of pseudostratified VA10 epithelium in the ALI setup depended on p63 expression and goblet cell differentiation, which can be induced by IL-13 stimulation, was abolished by the p63 knockdown. After knockdown of p63 in primary bronchial epithelial cells they did not proliferate and showed marked senescence. We conclude that these results strongly implicate p63 in the formation and maintenance of differentiated pseudostratified bronchial epithelium.

  14. Expressions of TRPVs in the cholesteatoma epithelium.

    Science.gov (United States)

    Do, Ba Hung; Koizumi, Hiroki; Ohbuchi, Toyoaki; Kawaguchi, Rintaro; Suzuki, Hideaki

    2017-10-01

    We have recently proposed a hypothesis that acid leakage through the cholesteatoma epithelium mediates bone resorption in middle ear cholesteatoma. In the present study, we investigated the expressions of transient receptor potential vanilloid (TRPV) channels, which have been shown to play roles in the regulation of epidermal barrier function, in the cholesteatoma epithelium in comparison with the normal skin. Cholesteatoma epithelium and postauricular skin were collected from 17 patients with primary acquired middle ear cholesteatoma who underwent tympanomastoidectomy. Expressions of TRPV1, TRPV3, TRPV4, and TRPV6 were explored by fluorescence immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). TRPV1, TRPV3, TRPV4, and TRPV6 mRNAs were all detected by qRT-PCR both in the skin and cholesteatoma tissue. Immunohistochemical staining showed that TRPV1 and TRPV3 were positive in the viable cell layers of the epidermis of the skin, and only TRPV3 was positive in those of the cholesteatoma epithelium. The immunoreactivity for TRPV3 was significantly weaker in cholesteatoma than in the skin. The lower expression of TRPV3 in cholesteatoma may be one of the mechanisms underlying the increased permeability of this tissue. On the other hand, TRPV1, TRPV4, and TRPV6 are unlikely to be involved in the regulation of epithelial permeability in cholesteatoma.

  15. Transport across the choroid plexus epithelium.

    Science.gov (United States)

    Praetorius, Jeppe; Damkier, Helle Hasager

    2017-06-01

    The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1 ) the choroid plexus epithelium as the source of mediators necessary for central nervous system development, 2 ) the choroid plexus as a route for microorganisms and immune cells into the central nervous system, and 3 ) the choroid plexus as a potential route for drug delivery into the central nervous system, bypassing the blood-brain barrier. Thus, the purpose of this review is to highlight current active areas of research in the choroid plexus physiology and a few matters of continuous controversy. Copyright © 2017 the American Physiological Society.

  16. Glucose, epithelium, and enteric nervous system: dialogue in the dark.

    Science.gov (United States)

    Pfannkuche, H; Gäbel, G

    2009-06-01

    The gastrointestinal epithelium is in close contact with the various components of the chymus, including nutrients, bacteria and toxins. The epithelial barrier has to decide which components are effectively absorbed and which components are extruded. In the small intestine, a nutrient like glucose is mainly absorbed by the sodium linked glucose cotransporter 1 (SGLT1) and the glucose transporter 2 (GLUT2). The expression and activity of both transport proteins is directly linked to the amount of intraluminal glucose. Besides the direct interaction between glucose and the enterocytes, glucose also stimulates different sensory mechanisms within the intestinal wall. The most important types of cells involved in the sensing of intraluminal contents are enteroendocrine cells and neurones of the enteric nervous system. Regarding glucosensing, a distinct type of enteroendocrine cells, the enterochromaffine (EC) cells are involved. Excitation of EC cells by intraluminal glucose results in the release of serotonin (5-HT), which modulates epithelial functions and activates enteric secretomotorneurones. Enteric neurones are not only activated by 5-HT, but also directly by glucose. The activation of different cell types and the subsequent crosstalk between these cells may trigger appropriate absorptive and secretory processes within the intestine.

  17. Neoplasia versus hyperplasia of the retinal pigment epithelium

    DEFF Research Database (Denmark)

    Heegaard, Steffen; Larsen, J.N.B.; Fledelius, Hans C.

    2001-01-01

    ophthalmology, retinal pigment epithelium, adenoma, tumor-like hyperplasia, histology, immunohistochemistry, tumor, neoplasm, ultrasonography......ophthalmology, retinal pigment epithelium, adenoma, tumor-like hyperplasia, histology, immunohistochemistry, tumor, neoplasm, ultrasonography...

  18. The Structure of Urethral Epithelium in Merinos Lambs

    Directory of Open Access Journals (Sweden)

    Vasile RUS

    2018-05-01

    Full Text Available The aim of this study was to investigate by histological techniques the structure of urethral epithelium in lambs. In this study, we harvested several fragments (prostatic, membranous and cavernous from urethra from 5 merino’s lambs of 3 months old. The first anatomical segment, the prostatic urethra, is lined by a urinary epithelium. The intermediary layer of this epithelium is formed of 5-6 rows of oval cells. The second segment of urethra has the same type of epithelium but the intermediary layer is formed of 6-7 rows of oval cells. In the last anatomical segment, the penile urethra, the epithelium is the same, but the intermediary layer has 3-4 rows of oval cells. In lambs, the urethra is lined by urinary epithelium. The urethral epithelium does not have the same thickness in all segments. The thinner epithelium it is in the cavernous urethra, the ticker is the membranous urethra.

  19. Embryo-epithelium interactions during implantation at a glance.

    Science.gov (United States)

    Aplin, John D; Ruane, Peter T

    2017-01-01

    At implantation, with the acquisition of a receptive phenotype in the uterine epithelium, an initial tenuous attachment of embryonic trophectoderm initiates reorganisation of epithelial polarity to enable stable embryo attachment and the differentiation of invasive trophoblasts. In this Cell Science at a Glance article, we describe cellular and molecular events during the epithelial phase of implantation in rodent, drawing on morphological studies both in vivo and in vitro, and genetic models. Evidence is emerging for a repertoire of transcription factors downstream of the master steroidal regulators estrogen and progesterone that coordinate alterations in epithelial polarity, delivery of signals to the stroma and epithelial cell death or displacement. We discuss what is known of the cell interactions that occur during implantation, before considering specific adhesion molecules. We compare the rodent data with our much more limited knowledge of the human system, where direct mechanistic evidence is hard to obtain. In the accompanying poster, we represent the embryo-epithelium interactions in humans and laboratory rodents, highlighting similarities and differences, as well as depict some of the key cell biological events that enable interstitial implantation to occur. © 2017. Published by The Company of Biologists Ltd.

  20. Angiography and the gastrointestinal bleeder

    International Nuclear Information System (INIS)

    Baum, S.

    1982-01-01

    The role of angiography in the diagnosis and treatment of gastrointestinal hemorrhage is discussed. Three categories of gastrointestinal bleeding are considered: upper gastrointestinal bleeding due to gastroesophageal varices, upper gastrointestinal bleeding of arterial or capillary origin, and lower gastrointestinal bleeding. The advantages and disadvantages of angiography are compared with those of radionuclide scanning and endoscopy or colonoscopy. It is anticipated that, as radionuclide scans are more widely employed, angiography will eventually be performed only in those patients with positive scans

  1. Microstructure imaging of human rectal mucosa using multiphoton microscopy

    Science.gov (United States)

    Liu, N. R.; Chen, G.; Chen, J. X.; Yan, J.; Zhuo, S. M.; Zheng, L. Q.; Jiang, X. S.

    2011-01-01

    Multiphoton microscopy (MPM) has high resolution and sensitivity. In this study, MPM was used to image microstructure of human rectal mucosa. The morphology and distribution of the main components in mucosa layer, absorptive cells and goblet cells in the epithelium, abundant intestinal glands in the lamina propria and smooth muscle fibers in the muscularis mucosa were clearly monitored. The variations of these components were tightly relevant to the pathology in gastrointestine system, especially early rectal cancer. The obtained images will be helpful for the diagnosis of early colorectal cancer.

  2. Effect of ageing on the gastro-intestinal transit of a lactulose-supplemented mixed solid-liquid meal in humans.

    Science.gov (United States)

    Wegener, M; Börsch, G; Schaffstein, J; Lüth, I; Rickels, R; Ricken, D

    1988-01-01

    Gastro-intestinal transit of a mixed solid-liquid meal containing wheat bread, scrambled eggs, coffee labelled with 99mTc, orange juice with lactulose and indigocarmine was evaluated in 21 young control (mean age 33.5 years) and 25 elderly subjects (mean age 81.7 years) without gastrointestinal complaints or severe medical illness. The rate of gastric emptying was determined by an anterior gamma camera technique, mouth-to-caecum transit by the hydrogen breath test and whole-gut transit by the first stool passage of indigocarmine. Gastric emptying was significantly prolonged in older subjects: t1/2 = 136 +/- (SEM) 13 versus 81 +/- 4 min; p less than 0.001. Concerning mouth-to-caecum or whole-gut transit time, significant differences between the two study groups were not detected.

  3. Melatonin and serotonin effects on gastrointestinal motility.

    Science.gov (United States)

    Thor, P J; Krolczyk, G; Gil, K; Zurowski, D; Nowak, L

    2007-12-01

    The gastrointestinal tract represents the most important extra pineal source of melatonin. Presence of melatonin (M) suggests that this hormone is somehow involved in digestive pathophysiology. Release of GI melatonin from serotonin-rich enterochromaffin EC cells of the GI mucosa suggest close antagonistic relationship with serotonin (S) and seem to be related to periodicity of food intake. Food deprivation resulted in an increase of tissue and plasma concentrations of M. Its also act as an autocrine and paracrine hormone affecting not only epithelium and immune system but also smooth muscle of the digestive tract. Low doses M improve gastrointestinal transit and affect MMC. M reinforce MMCs cyclic pattern but inhibits spiking bowel activity. Pharmacological doses of M delay gastric emptying via mechanisms that involve CCK2 and 5HT3 receptors. M released in response to lipid infusion exerts a modulatory influence that decreases the inhibitory effects of the ileal brake on gastric emptying. On isolated bowel S induces dose dependent increase in tone and reduction in amplitude of contraction which is affected by M. M reduced the tone but not amplitude or frequency of contraction. M is a promising therapeutic agent for IBS with activities independent of its effects on sleep, anxiety or depression. Since of its unique properties M could be considered for prevention or treatment of colorectal cancer, ulcerative colitis, gastric ulcers and irritable bowel syndrome.

  4. Apical serine protease activity is necessary for assembly of a high-resistance renal collecting duct epithelium

    DEFF Research Database (Denmark)

    Steensgaard, Mette; Svenningsen, Per; Tinning, Anne R

    2010-01-01

    Abstract AIM: We hypothesized that the serine protease prostasin is necessary for differentiation of a high resistance renal collecting duct epithelium governed by glucocorticoid. METHODS: Postnatal rat kidney and adult human kidney was used to study expression and localization of prostasin......-cadherin distribution did not change. CONCLUSION: Apical, GPI-anchored, lipid raft-associated serine protease activity, compatible with prostasin, is necessary for development of a high-resistance collecting duct epithelium....

  5. Prostaglandin E2 release from dermis regulates sodium permeability of frog skin epithelium

    DEFF Research Database (Denmark)

    Rytved, Klaus A.; Brodin, Birger; Nielsen, Robert

    1995-01-01

    Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium.......Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium....

  6. Intestinal epithelium in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Mehmet eCoskun

    2014-08-01

    Full Text Available The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs that are crucial in maintaining intestinal homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of inflammatory bowel disease (IBD. Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets.

  7. Quantification of transcriptome responses of the rumen epithelium to butyrate infusion

    Science.gov (United States)

    Short-chain fatty acids (SCFAs), such as butyrate, produced by gut microorganisms play an important role in energy metabolism and physiology in ruminants as well as in human health. Butyrate is a preferred substrate in the rumen epithelium where approximately 90% of butyrate is metabolized. Additi...

  8. Radiobiology of intestinal epithelium stem cells

    International Nuclear Information System (INIS)

    Konoplyannikova, O.A.

    1988-01-01

    After a single or three-fold whole body irradiation of mice with a dose of 4 Gy and the time interval for the proliferation to be restored (5 days or 3 weeks) the survival curve for stem cells of small intestine epithelium with regard to radiation dose was the same as that for non-preirradiated mice. This indicated that the proliferative potential of stem cells in these experimental conditions was not reduced

  9. Ethanol impedes embryo transport and impairs oviduct epithelium

    International Nuclear Information System (INIS)

    Xu, Tonghui; Yang, Qiuhong; Liu, Ruoxi; Wang, Wenfu; Wang, Shuanglian; Liu, Chuanyong; Li, Jingxin

    2016-01-01

    Most studies have demonstrated that alcohol consumption is associated with decreased fertility. The aim of this study was to investigate the effects of alcohol on pre-implantation embryo transport and/or early embryo development in the oviduct. We reported here that ethanol concentration-dependently suppressed the spontaneous motility of isolated human oviduct strips (EC50 50 ± 6 mM), which was largely attenuated in the present of L-NAME, a classical nitric oxide synthase(NOS) competitive inhibitor. Notably, either acute or chronic alcohol intake delayed egg transport and retarded early development of the embryo in the mouse oviduct, which was largely rescued by co-administration of L-NAME in a acute alcohol intake group but not in chronic alcohol intake group. It is worth mentioning that the oviductal epithelium destruction was verified by scanning electron microscope (SEM) observations in chronic alcohol intake group. In conclusion, alcohol intake delayed egg transport and retarded early development of the embryo in the oviduct by suppressing the spontaneous motility of oviduct and/or impairing oviductal epithelium. These findings suggested that alcohol abuse increases the incident of ectopic pregnancy.

  10. Ethanol impedes embryo transport and impairs oviduct epithelium.

    Science.gov (United States)

    Xu, Tonghui; Yang, Qiuhong; Liu, Ruoxi; Wang, Wenfu; Wang, Shuanglian; Liu, Chuanyong; Li, Jingxin

    2016-05-16

    Most studies have demonstrated that alcohol consumption is associated with decreased fertility. The aim of this study was to investigate the effects of alcohol on pre-implantation embryo transport and/or early embryo development in the oviduct. We reported here that ethanol concentration-dependently suppressed the spontaneous motility of isolated human oviduct strips (EC50 50±6mM), which was largely attenuated in the present of L-NAME, a classical nitric oxide synthase(NOS) competitive inhibitor. Notably, either acute or chronic alcohol intake delayed egg transport and retarded early development of the embryo in the mouse oviduct, which was largely rescued by co-administration of L-NAME in a acute alcohol intake group but not in chronic alcohol intake group. It is worth mentioning that the oviductal epithelium destruction was verified by scanning electron microscope (SEM) observations in chronic alcohol intake group. In conclusion, alcohol intake delayed egg transport and retarded early development of the embryo in the oviduct by suppressing the spontaneous motility of oviduct and/or impairing oviductal epithelium. These findings suggested that alcohol abuse increases the incident of ectopic pregnancy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Management of gastrointestinal hemorrhage.

    OpenAIRE

    Hilsden, R. J.; Shaffer, E. A.

    1995-01-01

    Acute gastrointestinal hemorrhage is a common problem that requires prompt recognition and management to prevent serious morbidity and mortality. Management goals are stabilization of the patient with vigorous fluid resuscitation followed by investigation and definitive treatment of the bleeding source. Endoscopy is often the initial diagnostic test and allows therapeutic measures to be performed at the same time.

  12. Regulation of UDP glucuronosyltransferases in the gastrointestinal tract

    International Nuclear Information System (INIS)

    Gregory, Philip A.; Lewinsky, Rikke H.; Gardner-Stephen, Dione A.; Mackenzie, Peter I.

    2004-01-01

    The UDP glucuronosyltransferases (UGT) of the gastrointestinal (GI) tract have a crucial role in protection against the toxic effects of lipophilic chemicals in the environment. UGTs such as UGT1A7, UGT1A8, and UGT1A10 are exclusively expressed in gastrointestinal tissues, each with a unique tissue distribution pattern that is subject to interindividual variation. The factors regulating this tissue-specific expression and that contribute to variability are beginning to be elucidated. Studies on the UGT1A7, 1A8, 1A9, and 1A10 gene promoters in Caco-2 cells, an in vitro model of enterocytes of the gastrointestinal tract, have identified the caudal homeodomain transcription factor, Cdx2, as an important regulator of the UGT1A8 and 1A10 gene proximal promoters. This transcription factor is found exclusively in the small intestine and colon: it is absent in the gastric epithelium and the esophagus. Cdx2 regulates the UGT1A8 and 1A10 promoters in cooperation with hepatocyte nuclear factor 1α (HNF1α). It is noteworthy that UGT1A7 is not expressed in gastrointestinal tissue distal to the gastric mucosa and does not contain a Cdx2 binding site in its proximal promoter. Transcription factors, including Sp1, which differentially bind to the initiator regions of the UGT1A8, 1A9, and 1A10 promoters, also contribute to the differences in expression of these UGTs in Caco-2 cells. The identification of important regulatory regions of UGT genes expressed in the gastrointestinal tract, and the transcription factors that bind to these regions, will aid in the elucidation of factors that contribute to interindividual differences in gastrointestinal UGT expression. In turn, this will lead to further understanding of interindividual variation in the capacity of the GI tract to metabolize lipophilic chemicals and to act as a barrier to dietary toxins and orally administered drugs

  13. Production of active pigment epithelium-derived factor inE. coli.

    Science.gov (United States)

    Zhang, Tao; Guan, Ming; Lu, Yuan

    2005-03-01

    Human pigment epithelium-derived factor (PEDF), a neurotrophic factor, is the most potent natural inhibitor of angiogenesis. To produce the active PEDF, the gene coding for the human PEDF protein was expressed in E. coli. The rPEDF protein was expressed at 457 mg l-1 as a soluble protein. The yield of purified GST fusion protein was 14 mg l-1. Purified rPEDF inhibited tube formation in endothelial cells.

  14. Respiratory distress associated with heterotopic gastrointestinal cysts of the oral cavity: A case report

    Directory of Open Access Journals (Sweden)

    Marco Antonio Méndez Sáenz

    2016-12-01

    Full Text Available Heterotopic gastrointestinal cysts of the oral cavity are benign lesions usually discovered during infancy. Their pathogenesis is not very clear. They are rare congenital anomalies that result from remnants of foregut-derived epithelium in the head, neck, thorax or abdomen during embryonic development. The majority of these lesions occur in the anterior ventral surface of the tongue and extend to the floor of the mouth. They are confused clinically by surgeons in cases of head and neck masses in children as ranulas, dermoid and thyroglossal cysts, and lymphangioma. We report the case of a 28-day newborn with a 3.6 cm oval mass on the floor of the mouth causing difficulty eating and cyanosis during crying. Complete surgical excision was performed by an oral approach under general anesthesia. Microscopic examination revealed gastric epithelium with tall columnar mucous cells on the surface and numerous short closed crypts, resembling fundal glands and mature gastric epithelium.

  15. DNA damage in lens epithelium of cataract patients in vivo and ex vivo.

    Science.gov (United States)

    Øsnes-Ringen, Oyvind; Azqueta, Amaia O; Moe, Morten C; Zetterström, Charlotta; Røger, Magnus; Nicolaissen, Bjørn; Collins, Andrew R

    2013-11-01

    DNA damage has been described in the human cataractous lens epithelium, and oxidative stress generated by UV radiation and endogenous metabolic processes has been suggested to play a significant role in the pathogenesis of cataract. In this study, the aim was to explore the quality and relative quantity of DNA damage in lens epithelium of cataract patients in vivo and after incubation in a cell culture system. Capsulotomy specimens were analysed, before and after 1 week of ex vivo cultivation, using the comet assay to measure DNA strand breaks, oxidized purine and pyrimidine bases and UV-induced cyclobutane pyrimidine dimers. DNA strand breaks were barely detectable, oxidized pyrimidines and pyrimidine dimers were present at low levels, whereas there was a relatively high level of oxidized purines, which further increased after cultivation. The observed levels of oxidized purines in cataractous lens epithelium may support a theory consistent with light damage and oxidative stress as mediators of molecular damage to the human lens epithelium. Damage commonly associated with UV-B irradiation was relatively low. The levels of oxidized purines increased further in a commonly used culture system. This is of interest considering the importance and versatility of ex vivo systems in studies exploring the pathogenesis of cataract. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

  16. Pharmacokinetics of trefoil peptides and their stability in gastrointestinal contents

    DEFF Research Database (Denmark)

    Kjellev, Stine; Vestergaard, Else Marie; Nexø, Ebba

    2007-01-01

    Trefoil factor family (TFF) peptides are considered promising for therapeutic use in gastrointestinal diseases, and there is a need to explore the fate of injected TFF and the stability of the peptides in the gastrointestinal tract. We studied the pharmacokinetics of intravenously (i.v.) administ......Trefoil factor family (TFF) peptides are considered promising for therapeutic use in gastrointestinal diseases, and there is a need to explore the fate of injected TFF and the stability of the peptides in the gastrointestinal tract. We studied the pharmacokinetics of intravenously (i.......v.) administered hTFF2 in mice and rats and of hTFF3 administered i.v., intramuscularly, intraperitoneally, and subcutaneously in mice, and estimated by ELISA the decay of the peptides added to rat and human gastrointestinal contents. We found that i.v. injected hTFF2 and hTFF3 were cleared from the circulation...

  17. GASTROINTESTINAL STROMAL TUMOR (GIST

    Directory of Open Access Journals (Sweden)

    Luigi eTornillo

    2014-11-01

    Full Text Available Gastrointestinal stromal tumors are the most frequent mesenchymal tumors of the gastrointestinal tract. The discovery that these tumors, formerly thought of smooth muscle origin, are indeed better characterized by specific activating mutation in genes coding for the receptor tyrosine kinases CKIT and PDGFRA and that these mutations are strongly predictive for the response to targeted therapy with receptor tyrosine kinase inhibitors has made GISTs the typical example of the integration of basic molecular knowledge in the daily clinical activity. The information on the mutational status of these tumors is essential to predict (and subsequently to plan the therapy. As resistant cases are frequently wild-type, other possible oncogenic events, defining other entities, have been discovered (e.g. succinil dehydrogenase mutation/dysregulation, insuline growth factor expression, mutations in the RAS-RAF-MAPK pathway. The classification of disease must nowadays rely on the integration of the clinico-morphological characteristics with the molecular data.

  18. Radiology illustrated. Gastrointestinal tract

    International Nuclear Information System (INIS)

    Choi, Byung Ihn

    2015-01-01

    Radiology Illustrated: Gastrointestinal Tract is the second of two volumes designed to provide clear and practical guidance on the diagnostic imaging of abdominal diseases. The book presents approximately 300 cases with 1500 carefully selected and categorized illustrations of gastrointestinal tract diseases, along with key text messages and tables that will help the reader easily to recall the relevant images as an aid to differential diagnosis., Essential points are summarized at the end of each text message to facilitate rapid review and learning. Additionally, brief descriptions of each clinical problem are provided, followed by case studies of both common and uncommon pathologies that illustrate the roles of the different imaging modalities, including ultrasound, radiography, computed tomography, and magnetic resonance imaging.

  19. Radiology illustrated. Gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Byung Ihn (ed.) [Seoul National University Hospital (Korea, Republic of). Dept. of Radiology

    2015-02-01

    Radiology Illustrated: Gastrointestinal Tract is the second of two volumes designed to provide clear and practical guidance on the diagnostic imaging of abdominal diseases. The book presents approximately 300 cases with 1500 carefully selected and categorized illustrations of gastrointestinal tract diseases, along with key text messages and tables that will help the reader easily to recall the relevant images as an aid to differential diagnosis., Essential points are summarized at the end of each text message to facilitate rapid review and learning. Additionally, brief descriptions of each clinical problem are provided, followed by case studies of both common and uncommon pathologies that illustrate the roles of the different imaging modalities, including ultrasound, radiography, computed tomography, and magnetic resonance imaging.

  20. Gastrointestinal Complications of Obesity

    Science.gov (United States)

    Camilleri, Michael; Malhi, Harmeet; Acosta, Andres

    2017-01-01

    Obesity usually is associated with morbidity related to diabetes mellitus and cardiovascular diseases. However, there are many gastrointestinal and hepatic diseases for which obesity is the direct cause (eg, nonalcoholic fatty liver disease) or is a significant risk factor, such as reflux esophagitis and gallstones. When obesity is a risk factor, it may interact with other mechanisms and result in earlier presentation or complicated diseases. There are increased odds ratios or relative risks of several gastrointestinal complications of obesity: gastroesophageal reflux disease, erosive esophagitis, Barrett’s esophagus, esophageal adenocarcinoma, erosive gastritis, gastric cancer, diarrhea, colonic diverticular disease, polyps, cancer, liver disease including nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, gallstones, acute pancreatitis, and pancreatic cancer. Gastroenterologists are uniquely poised to participate in the multidisciplinary management of obesity as physicians caring for people with obesity-related diseases, in addition to their expertise in nutrition and endoscopic interventions. PMID:28192107

  1. Gastrointestinal food allergies.

    Science.gov (United States)

    Heine, Ralf G

    2015-01-01

    Gastrointestinal food allergies present during early childhood with a diverse range of symptoms. Cow's milk, soy and wheat are the three most common gastrointestinal food allergens. Several clinical syndromes have been described, including food protein-induced enteropathy, proctocolitis and enterocolitis. In contrast with immediate, IgE-mediated food allergies, the onset of gastrointestinal symptoms is delayed for at least 1-2 hours after ingestion in non-IgE-mediated allergic disorders. The pathophysiology of these non-IgE-mediated allergic disorders is poorly understood, and useful in vitro markers are lacking. The results of the skin prick test or measurement of the food-specific serum IgE level is generally negative, although low-positive results may occur. Diagnosis therefore relies on the recognition of a particular clinical phenotype as well as the demonstration of clear clinical improvement after food allergen elimination and the re-emergence of symptoms upon challenge. There is a significant clinical overlap between non-IgE-mediated food allergy and several common paediatric gastroenterological conditions, which may lead to diagnostic confusion. The treatment of gastrointestinal food allergies requires the strict elimination of offending food allergens until tolerance has developed. In breast-fed infants, a maternal elimination diet is often sufficient to control symptoms. In formula-fed infants, treatment usually involves the use an extensively hydrolysed or amino acid-based formula. Apart from the use of hypoallergenic formulae, the solid diets of these children also need to be kept free of specific food allergens, as clinically indicated. The nutritional progress of infants and young children should be carefully monitored, and they should undergo ongoing, regular food protein elimination reassessments by cautious food challenges to monitor for possible tolerance development. © 2015 S. Karger AG, Basel.

  2. Upper gastrointestinal bleeding.

    Science.gov (United States)

    Feinman, Marcie; Haut, Elliott R

    2014-02-01

    Upper gastrointestinal (GI) bleeding remains a commonly encountered diagnosis for acute care surgeons. Initial stabilization and resuscitation of patients is imperative. Stable patients can have initiation of medical therapy and localization of the bleeding, whereas persistently unstable patients require emergent endoscopic or operative intervention. Minimally invasive techniques have surpassed surgery as the treatment of choice for most upper GI bleeding. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Cytokeratin expression in mouse lacrimal gland germ epithelium.

    Science.gov (United States)

    Hirayama, Masatoshi; Liu, Ying; Kawakita, Tetsuya; Shimmura, Shigeto; Tsubota, Kazuo

    2016-05-01

    The lacrimal gland secretes tear fluids that protect the ocular surface epithelium, and its dysfunction leads to dry eye disease (DED). The functional restoration of the lacrimal gland by engraftment of a bioengineered lacrimal gland using lacrimal gland germ epithelial cells has been proposed to cure DED in mice. Here, we investigate the expression profile of cytokeratins in the lacrimal gland germ epithelium to clarify their unique characteristics. We performed quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC) analysis to clarify the expression profile of cytokeratin in the lacrimal gland germ epithelium. The mRNA expression of keratin (KRT) 5, KRT8, KRT14, KRT15, and KRT18 in the lacrimal gland germ epithelium was increased compared with that in mouse embryonic stem cells and the lacrimal gland germ mesenchyme, as analyzed by Q-PCR. The expression level of KRT15 increased in the transition from stem cells to lacrimal gland germ epithelium, then decreased as the lacrimal gland matured. IHC revealed that the expression set of these cytokeratins in the lacrimal gland germ epithelium was different from that in the adult lacrimal gland. The expression of KRT15 was observed in the lacrimal gland germ epithelium, and it segmentalized into some of the basal cells in the intercanulated duct in mature gland. We determined the expression profile of cytokeratins in the lacrimal gland epithelium, and identified KRT15 as a candidate unique cellular marker for the lacrimal gland germ epithelium. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Orexins and gastrointestinal functions.

    Science.gov (United States)

    Baccari, M C

    2010-03-01

    Orexin A (OXA) and orexin B (OXB) are recently discovered neuropeptides that appear to play a role in various distinct functions such as arousal and the sleep-wake cycle as well as on appetite and regulation of feeding and energy homeostasis. Orexins were first described as neuropeptides expressed by a specific population of neurons in the lateral hypothalamic area, a region classically implicated in feeding behaviour. Orexin neurons project to numerous brain regions, where orexin receptors have been shown to be widely distributed: both OXA and OXB act through two subtypes of receptors (OX1R and OX2R) that belong to the G protein-coupled superfamily of receptors. Growing evidence indicates that orexins act in the central nervous system also to regulate gastrointestinal functions: animal studies have indeed demonstrated that centrally-injected orexins or endogenously released orexins in the brain stimulates gastric secretion and influence gastrointestinal motility. The subsequent identification of orexins and their receptors in the enteric nervous system (including the myenteric and the submucosal plexuses) as well as in mucosa and smooth muscles has suggested that these neuropeptides may also play a local action. In this view, emerging studies indicate that orexins also exert region-specific contractile or relaxant effects on isolated gut preparations. The aim of the proposed review is to summarize both centrally- and peripherally-mediated actions of orexins on gastrointestinal functions and to discuss the related physiological role on the basis of the most recent findings.

  5. Bacillus licheniformis in geogenic dust induces inflammation in respiratory epithelium.

    Science.gov (United States)

    Pickering, Janessa; Teo, Teck Hui; Thornton, Ruth B; Kirkham, Lea-Ann; Zosky, Graeme R; Clifford, Holly D

    2018-07-01

    Exposure to environmental geogenic (or earth-derived) dust can lead to more frequent and severe infections in the human airway. Particulate matter respiratory diseases. We have previously demonstrated that mice exposed to geogenic dust PM 10 experienced an exacerbation of inflammatory responses to influenza A virus. Whether geogenic dust PM 10 also exacerbates respiratory bacterial infection is not yet known, nor are the components of the dust that drive these responses. We treated airway bronchial epithelial cells (NuLi-1) with UV-irradiated geogenic dust PM 10 from six remote Western Australian towns. High levels of IL-6 and IL-8 production were observed, as well as persistent microbial growth. 16 S rRNA sequencing of the growth identified the microbe as Bacillus licheniformis, a spore-forming, environmentally abundant bacterium. We next investigated the interaction of B. licheniformis with respiratory epithelium in vitro to determine whether this exacerbated infection with a bacterial respiratory pathogen (non-typeable Haemophilus influenzae, NTHi). Heat treatment (100 °C) of all PM 10 samples eliminated B. licheniformis contamination and reduced epithelial inflammatory responses, suggesting that heat-labile and/or microbial factors were involved in the host response to geogenic dust PM 10 . We then exposed NuLi-1 epithelium to increasing doses of the isolated Bacillus licheniformis (multiplicity of infection of 10:1, 1:1 or 0.1:1 bacteria: cells) for 1, 3, and 24 h. B. licheniformis and NTHi infection (association and invasion) was assessed using a standard gentamicin survival assay, and epithelial release of IL-6 and IL-8 was measured using a bead based immunoassay. B. licheniformis was cytotoxic to NuLi-1 cells at 24 h. At 3 h post-challenge, B. licheniformis elicited high IL-6 and IL-8 inflammatory responses from NuLi-1 cells compared with cells treated with heat-treated geogenic dust PM 10 (p respiratory epithelium. The impact on respiratory

  6. Comparison of Expression Profiles in Ovarian Epithelium In Vivo and Ovarian Cancer Identifies Novel Candidate Genes Involved in Disease Pathogenesis

    Science.gov (United States)

    Emmanuel, Catherine; Gava, Natalie; Kennedy, Catherine; Balleine, Rosemary L.; Sharma, Raghwa; Wain, Gerard; Brand, Alison; Hogg, Russell; Etemadmoghadam, Dariush; George, Joshy; Birrer, Michael J.; Clarke, Christine L.; Chenevix-Trench, Georgia; Bowtell, David D. L.; Harnett, Paul R.; deFazio, Anna

    2011-01-01

    Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute

  7. Surface Proteins of Lactococcus lactis: Bacterial Resources for Muco-adhesion in the Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Muriel Mercier-Bonin

    2017-11-01

    Full Text Available Food and probiotic bacteria, in particular lactic acid bacteria, are ingested in large amounts by humans and are part of the transient microbiota which is increasingly considered to be able to impact the resident microbiota and thus possibly the host health. The lactic acid bacterium Lactococcus lactis is extensively used in starter cultures to produce dairy fermented food. Also because of a generally recognized as safe status, L. lactis has been considered as a possible vehicle to deliver in vivo therapeutic molecules with anti-inflammatory properties in the gastrointestinal tract. One of the key factors that may favor health effects of beneficial bacteria to the host is their capacity to colonize transiently the gut, notably through close interactions with mucus, which covers and protects the intestinal epithelium. Several L. lactis strains have been shown to exhibit mucus-binding properties and bacterial surface proteins have been identified as key determinants of such capacity. In this review, we describe the different types of surface proteins found in L. lactis, with a special focus on mucus-binding proteins and pili. We also review the different approaches used to investigate the adhesion of L. lactis to mucus, and particularly to mucins, one of its major components, and we present how these approaches allowed revealing the role of surface proteins in muco-adhesion.

  8. Epithelium-innate immune cell axis in mucosal responses to SIV.

    Science.gov (United States)

    Shang, L; Duan, L; Perkey, K E; Wietgrefe, S; Zupancic, M; Smith, A J; Southern, P J; Johnson, R P; Haase, A T

    2017-03-01

    In the SIV (simian immunodeficiency virus)-rhesus macaque model of HIV-1 (human immunodeficiency virus type I) transmission to women, one hallmark of the mucosal response to exposure to high doses of SIV is CD4 T-cell recruitment that fuels local virus expansion in early infection. In this study, we systematically analyzed the cellular events and chemoattractant profiles in cervical tissues that precede CD4 T-cell recruitment. We show that vaginal exposure to the SIV inoculum rapidly induces chemokine expression in cervical epithelium including CCL3, CCL20, and CXCL8. The chemokine expression is associated with early recruitment of macrophages and plasmacytoid dendritic cells that are co-clustered underneath the cervical epithelium. Production of chemokines CCL3 and CXCL8 by these cells in turn generates a chemokine gradient that is spatially correlated with the recruitment of CD4 T cells. We further show that the protection of SIVmac239Δnef vaccination against vaginal challenge is correlated with the absence of this epithelium-innate immune cell-CD4 T-cell axis response in the cervical mucosa. Our results reveal a critical role for cervical epithelium in initiating early mucosal responses to vaginal infection, highlight an important role for macrophages in target cell recruitment, and provide further evidence of a paradoxical dampening effect of a protective vaccine on these early mucosal responses.

  9. Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1

    Directory of Open Access Journals (Sweden)

    Anja Meyer

    2017-04-01

    Full Text Available Niemann–Pick disease type C1 (NPC1 is a fatal neurovisceral lysosomal lipid storage disorder. The mutation of the NPC1 protein affects the homeostasis and transport of cholesterol and glycosphingolipids from late endosomes/lysosomes to the endoplasmic reticulum resulting in progressive neurodegeneration. Since olfactory impairment is one of the earliest symptoms in many neurodegenerative disorders, we focused on alterations of the olfactory epithelium in an NPC1 mouse model. Previous findings revealed severe morphological and immunohistochemical alterations in the olfactory system of NPC1−/− mutant mice compared with healthy controls (NPC1+/+. Based on immunohistochemical evaluation of the olfactory epithelium, we analyzed the impact of neurodegeneration in the olfactory epithelium of NPC1−/− mice and observed considerable loss of mature olfactory receptor neurons as well as an increased number of proliferating and apoptotic cells. Additionally, after administration of two different therapy approaches using either a combination of miglustat, 2-hydroxypropyl-β-cyclodextrin (HPβCD and allopregnanolone or a monotherapy with HPβCD, we recorded a remarkable reduction of morphological damages in NPC1−/− mice and an up to four-fold increase of proliferating cells within the olfactory epithelium. Numbers of mature olfactory receptor neurons doubled after both therapy approaches. Interestingly, we also observed therapy-induced alterations in treated NPC1+/+ controls. Thus, olfactory testing may provide useful information to monitor pharmacologic treatment approaches in human NPC1.

  10. Detoxification of carbaryl by anaerobic gastrointestinal organisms

    International Nuclear Information System (INIS)

    Laszewski, S.J.; Harkin, J.M.

    1990-01-01

    Bacteria originating from the human gastrointestinal tract (GIT) were tested in vitro for their ability to hydrolyze carbaryl, the most widely used carbamate insecticide. Carbaryl hydrolysis prevents acetylcholinesterase inhibition. Degradation of [1- 14 C]naphthyl N-methylcarbamate was assessed through the use of carbon-and nitrogen-free enrichment cultures as well as a cometabolic enrichment culture. The carbon-free enrichment culture showed the greatest ability to hydrolyze carbaryl. Two facultative anaerobes, identified as DF-3 and Citrobacter freundii were isolated. Cell-free extracts from these bacteria were able to hydrolyze p-nitrophenyl acetate, 1-naphthyl acetate and carbaryl. This investigation suggests carbaryl degradation could occur prior to gastrointestinal absorption. Human GIT organisms are also widespread in anaerobic environments. Microbial hydrolysis of a xenobiotic can be an important reaction in the anaerobic environments of man or nature

  11. Significant Association of Streptococcus bovis with Malignant Gastrointestinal Diseases

    Directory of Open Access Journals (Sweden)

    Salah Shanan

    2011-01-01

    Full Text Available Streptococcus bovis is a Gram-positive bacterium causing serious human infections, including endocarditis and bacteremia, and is usually associated with underlying disease. The aims of the current study were to compare prevalence of the bacterium associated with malignant and nonmalignant gastrointestinal diseases and to determine the susceptibility of the isolated strains to different antimicrobial agents. The result showed that the prevalence of S. bovis in stool specimens from patients with malignant or with nonmalignant gastrointestinal diseases was statistically significant. This result may support the idea that there is correlation between S. bovis and the malignant gastrointestinal diseases.

  12. Challenges and opportunities for tissue-engineering polarized epithelium.

    Science.gov (United States)

    Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

    2014-02-01

    The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

  13. Embolization for gastrointestinal hemorrhages

    International Nuclear Information System (INIS)

    Kraemer, S.C.; Goerich, J.; Rilinger, N.; Aschoff, A.J.; Vogel, J.; Brambs, H.J.; Siech, M.

    2000-01-01

    Retrospective evaluation of interventional embolization therapy in the treatment of gastrointestinal hemorrhage over a long-term observation period from 1989 to 1997. Included in the study were 35 patients (age range 18-89 years) with gastrointestinal bleeding (GI) referred for radiological intervention either primarily or following unsuccessful endoscopy or surgery. Sources of GI bleeding included gastric and duodenal ulcers (n = 7), diverticula (n = 3), erosion of the intestinal wall secondary to malignancy (n = 6), vascular malformations (n = 4), and hemorrhoids (n = 2), as well as from postoperative (n = 6), posttraumatic (n = 2), postinflammatory (n = 4) or unknown (n = 1) causes. Ethibloc (12 cases) or metal coils (14 cases) were predominantly used as embolisates. In addition, combinations of tissue adhesive and gelfoam particles and of coils and Ethibloc were used (six cases). Finally, polyvinyl alcohol particles, a coated stent, and an arterial wire dissection were utilized in one case each. Bleeding was stopped completely in 29 of 35 cases (83 %). In one case (3 %) the source of bleeding was recognized but the corresponding vessel could not be catheterized. In five other cases (14 %) there was partial success with reduced, though still persistent, bleeding. The rate of complications was 14 %, including four instances of intestinal ischemia with fatal outcome in the first years, and, later, one partial infarction of the spleen without serious consequences. Gastrointestinal hemorrhage can be controlled in a high percentage of patients, including the seriously ill and those who had previously undergone surgery, with the use of minimally invasive interventional techniques. The availability of minicoils instead of fluid embolization agents has reduced the risk of serious complications. (orig.)

  14. Embolization for gastrointestinal hemorrhages

    Energy Technology Data Exchange (ETDEWEB)

    Kraemer, S.C.; Goerich, J.; Rilinger, N.; Aschoff, A.J.; Vogel, J.; Brambs, H.J. [Dept. of Diagnostic Radiology, University of Ulm (Germany); Siech, M. [Dept. of Abdominal Surgery, University of Ulm (Germany)

    2000-05-01

    Retrospective evaluation of interventional embolization therapy in the treatment of gastrointestinal hemorrhage over a long-term observation period from 1989 to 1997. Included in the study were 35 patients (age range 18-89 years) with gastrointestinal bleeding (GI) referred for radiological intervention either primarily or following unsuccessful endoscopy or surgery. Sources of GI bleeding included gastric and duodenal ulcers (n = 7), diverticula (n = 3), erosion of the intestinal wall secondary to malignancy (n = 6), vascular malformations (n = 4), and hemorrhoids (n = 2), as well as from postoperative (n = 6), posttraumatic (n = 2), postinflammatory (n = 4) or unknown (n = 1) causes. Ethibloc (12 cases) or metal coils (14 cases) were predominantly used as embolisates. In addition, combinations of tissue adhesive and gelfoam particles and of coils and Ethibloc were used (six cases). Finally, polyvinyl alcohol particles, a coated stent, and an arterial wire dissection were utilized in one case each. Bleeding was stopped completely in 29 of 35 cases (83 %). In one case (3 %) the source of bleeding was recognized but the corresponding vessel could not be catheterized. In five other cases (14 %) there was partial success with reduced, though still persistent, bleeding. The rate of complications was 14 %, including four instances of intestinal ischemia with fatal outcome in the first years, and, later, one partial infarction of the spleen without serious consequences. Gastrointestinal hemorrhage can be controlled in a high percentage of patients, including the seriously ill and those who had previously undergone surgery, with the use of minimally invasive interventional techniques. The availability of minicoils instead of fluid embolization agents has reduced the risk of serious complications. (orig.)

  15. in upper gastrointestinal endoscopy

    Directory of Open Access Journals (Sweden)

    Sinan Uzman

    2016-07-01

    Full Text Available Introduction : There is increasing interest in sedation for upper gastrointestinal endoscopy (UGE. Prospective randomized studies comparing sedation properties and complications of propofol and midazolam/meperidine in upper gastrointestinal endoscopy (UGE are few. Aim: To compare propofol and midazolam/meperidine sedation for UGE in terms of cardiopulmonary side effects, patient and endoscopist satisfaction and procedure-related times. Material and methods: This was a prospective, randomized, double-blind study of propofol versus midazolam and meperidine in 100 patients scheduled for diagnostic upper gastrointestinal endoscopy. The patients were divided into propofol and midazolam/meperidine groups. Randomization was generated by a computer. Cardiopulmonary side effects (hypotension, bradycardia, hypoxemia, procedure-related times (endoscopy time, awake time, time to hospital discharge, and patient and endoscopist satisfaction were compared between groups. Results: There was no significant difference between the groups with respect to the cost, endoscopy time, or demographic and clinical characteristics of the patients. Awake time and time to hospital discharge were significantly shorter in the propofol group (6.58 ±4.72 vs. 9.32 ±4.26 min, p = 0.030 and 27.60 ±7.88 vs. 32.00 ±10.54 min, p = 0.019. Hypotension incidence was significantly higher in the propofol group (12% vs. 0%, p = 0.027. The patient and endoscopist satisfaction was better with propofol. Conclusions : Propofol may be preferred to midazolam/meperidine sedation, with a shorter awake and hospital discharge time and better patient and endoscopist satisfaction. However, hypotension risk should be considered with propofol, and careful evaluation is needed, particularly in cardiopulmonary disorders.

  16. Gastrointestinal Headache; a Narrative Review

    OpenAIRE

    Majid T Noghani; Hossein Rezaeizadeh; Sayed Mohammad Baqer Fazljoo; Mahmoud Yousefifard; Mansoor Keshavarz

    2016-01-01

    There are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report resolution of headache following the treatment of the associated gastrointestinal disorder. Headache disorders are classified by The International Headache Society as primary or secondary; however, among the secondary headaches, those attributed to gastrointestinal disorders are not appreciated. Therefore, we aimed to review the literature to provide evidence for headaches, which or...

  17. Gastrointestinal and hepatobiliary radiology

    International Nuclear Information System (INIS)

    Graham, R.N.J.; Perriss, R.W.; Scarsbrook, A.F.

    2006-01-01

    This is the fifth in the series of short reviews of internet-based radiological learning resources and will focus on gastrointestinal (GI) and hepatobiliary radiology. Below are details of a few of the higher quality resources currently available. Most of the sites cater for medical students and trainee or non-specialist radiologists, but may be also be of interest to specialists, especially for use in teaching. Hyperlinks are available in the electronic version of this article and were all active at the time of going to press (May 2006)

  18. Gastrointestinal stromal tumors

    International Nuclear Information System (INIS)

    Sufliarsky, J.

    2011-01-01

    Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract. Better understanding of the molecular characteristics of GISTs led to the clinical development of imatinib for treating patients with this disease. New immuno markers and mechanisms of primary and secondary resistance were discovered. Adjuvant imatinib in intermediate or high risk GIST has improved the recurrence-free survival. Sunitinib in patients with intolerance or progression on imatinib demonstrated significant improvements in progression-free and overall survival versus placebo. Second-generation tyrosine kinase inhibitors, such as sorafenib, dasatinib, and nilotinib, have shown activity in patients with imatinib- and sunitinib-resistant GIST. (author)

  19. Gastrointestinal Manifestations of Cystic Fibrosis

    Science.gov (United States)

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  20. Mechanosensitive Piezo Channels in the Gastrointestinal Tract.

    Science.gov (United States)

    Alcaino, C; Farrugia, G; Beyder, A

    2017-01-01

    Sensation of mechanical forces is critical for normal function of the gastrointestinal (GI) tract and abnormalities in mechanosensation are linked to GI pathologies. In the GI tract there are several mechanosensitive cell types-epithelial enterochromaffin cells, intrinsic and extrinsic enteric neurons, smooth muscle cells and interstitial cells of Cajal. These cells use mechanosensitive ion channels that respond to mechanical forces by altering transmembrane ionic currents in a process called mechanoelectrical coupling. Several mechanosensitive ionic conductances have been identified in the mechanosensory GI cells, ranging from mechanosensitive voltage-gated sodium and calcium channels to the mechanogated ion channels, such as the two-pore domain potassium channels K2P (TREK-1) and nonselective cation channels from the transient receptor potential family. The recently discovered Piezo channels are increasingly recognized as significant contributors to cellular mechanosensitivity. Piezo1 and Piezo2 are nonselective cationic ion channels that are directly activated by mechanical forces and have well-defined biophysical and pharmacologic properties. The role of Piezo channels in the GI epithelium is currently under investigation and their role in the smooth muscle syncytium and enteric neurons is still not known. In this review, we outline the current state of knowledge on mechanosensitive ion channels in the GI tract, with a focus on the known and potential functions of the Piezo channels. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Metabolism of the Lignan Macromolecule into Enterolignans in the Gastrointestinal Lumen As Determined in the Simulator of the Human Intestinal Microbial Ecosystem

    NARCIS (Netherlands)

    Eeckhaut, E.; Struijs, K.; Possemiers, S.; Vincken, J.P.; Keukeleire, de D.; Verstraete, W.

    2008-01-01

    Estrogenic plant compounds from the human diet such as the lignan secoisolariciresinol diglucoside (SDG, 1) can exert biological activity in the human body upon ingestion and bioactivation to enterodiol (END, 5) and enterolactone (ENL, 6). Bioavailability of lignans is influenced by the food matrix

  2. Glycemic Responses, Appetite Ratings and Gastrointestinal Hormone Responses of Most Common Breads Consumed in Spain. A Randomized Control Trial in Healthy Humans

    Directory of Open Access Journals (Sweden)

    Carolina Gonzalez-Anton

    2015-05-01

    Full Text Available The present study was carried out to determine the glycemic index (GI, glycemic load (GL, insulinemic index (InI, appetite ratings and postprandial plasma concentrations of gastrointestinal hormones related to the control of food intake after the ingestion of the five most common breads consumed in Spain with different compositions and manufacturing processes. Twenty-two healthy adults participated in a randomized crossover study. The breads tested were Ordinary, Precooked-Frozen, Candeal-flour, Alfacar whites and Wholemeal. All breads portions were calculated to supply 50 g of available carbohydrates. In addition, 50 g of glucose was used as a reference. A linear mixed-effects model was used to compare data calculated for all breads with glucose load. The GI value varied from 61 for the Wholemeal, to Alfacar 68, Ordinary 76, and 78 and 86 for the Precooked-Frozen and Candeal-flour breads, respectively. Wholemeal and Alfacar had lower GI than glucose. All tested breads had a lower GL (ranged 9 to 18 compared with glucose. Wholemeal GL was similar to Alfacar, but lower than the other white breads. InI were significantly lower for all breads (ranged 68 to 73 compared with glucose, and similar among them. The intake of the Wholemeal bread led to a higher release of gastric inhibitory polypeptide compared with the Ordinary and Precooked breads and to a higher release of pancreatic polypeptide compared with the Precooked-Frozen bread. All breads affected appetite ratings similarly. In conclusion, based on GL, the Wholemeal bread would be expected to exert a favorable glycemic response.

  3. Gastrointestinal Eosinofilic Disorders

    International Nuclear Information System (INIS)

    Rodriguez Maria, Roberto; Bohorquez, Maria Amalia; Gonzalez, Irene; Torregroza, Gustavo

    2007-01-01

    The gastrointestinal eosinofilic disorders are little frequent diseases, of etiopatogenia little clear, that are characterized by the presence of an infiltrated eosinofilo that can affect the different layers of the wall of the alimentary canal in absence of known causes of eosinofilia. The clinical manifestations are variable and the symptoms are conditioned by the degree of eosinofilia of the wall, the number of layers affected and the segment of the gastrointestinal tract implied. The presentations symptoms vary from diarrhea, vomits, abdominal pain and loss of weigh until the acute intestinal obstruction. They are characterized to present peripherical eosinofilia, although it is not a forced criterion. Its definite diagnosis is anatomopatologic. The steroid use is considered as the angular stone of the treatment. We present two cases, with different clinical presentation forms, with initial answer to steroids and later relapse after the suspension of these, remaining without symptoms actually with dependency of low doses of steroids. Next we will do the revision of the available literature emphasizing the pathophysiologic data, the clinical evaluation and the therapeutic aspects

  4. Gastrointestinal medications and breastfeeding.

    Science.gov (United States)

    Hagemann, T M

    1998-09-01

    Medications used to treat gastrointestinal symptoms are increasingly being used as more have been gained nonprescription status. Most of the gastrointestinal medications, such as laxatives, antacids, and antidiarrheal agents, are used short term. Women who breastfeed should be aware of the risks of taking any medications, whether prescription or nonprescription. There is little information describing transfer into breast milk for many of these products. Cimetidine, atropine, cascara, cisapride, loperamide, magnesium sulfate, and senna are the only products identified by the AAP as compatible with breast feeding. Metoclopramide is listed by the AAP as a drug whose effect on nursing infants is unknown but may be of potential concern, although studies published to date have not reported any adverse effects. The safest laxatives and antidiarrheals are those that are not absorbed and should be considered first-line therapy for conditions of constipation or loose stools. Famotidine and nizatidine are excreted into breast milk to a lesser extent than cimetidine or ranitidine and may be the preferred histamine antagonists. Despite the limited data on the use of cisapride in nursing women, it is considered safe by the AAP and may be preferred over metoclopramide for first-line prescription treatment of heartburn. Although most of these agents appear safe in the nursing infant, caretakers should be aware of the potential adverse reactions that may occur in infants whose mothers require these products.

  5. File list: Unc.Oth.10.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.10.AllAg.Olfactory_epithelium mm9 Unclassified Others Olfactory epithelium ...SRX112960 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.10.AllAg.Olfactory_epithelium.bed ...

  6. File list: Unc.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.20.AllAg.Olfactory_epithelium mm9 Unclassified Others Olfactory epithelium ...SRX112960 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.20.AllAg.Olfactory_epithelium.bed ...

  7. File list: Unc.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.05.AllAg.Olfactory_epithelium mm9 Unclassified Others Olfactory epithelium ...SRX112960 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.05.AllAg.Olfactory_epithelium.bed ...

  8. Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: Stimulation of interleukin-8 secretion, potentiation of interleukin-1β effect and increase in the transepithelial passage of commensal bacteria

    International Nuclear Information System (INIS)

    Maresca, Marc; Yahi, Nouara; Younes-Sakr, Lama; Boyron, Marilyn; Caporiccio, Bertrand; Fantini, Jacques

    2008-01-01

    Mycotoxins are fungal secondary metabolites responsible of food-mediated intoxication in animals and humans. Deoxynivalenol, ochratoxin A and patulin are the best known enteropathogenic mycotoxins able to alter intestinal functions resulting in malnutrition, diarrhea, vomiting and intestinal inflammation in vivo. Although their effects on intestinal barrier and transport activities have been extensively characterized, the mechanisms responsible for their pro-inflammatory effect are still poorly understood. Here we investigated if mycotoxin-induced intestinal inflammation results from a direct and/or indirect pro-inflammatory activity of these mycotoxins on human intestinal epithelial cells, using differentiated Caco-2 cells as model and interleukin 8 (IL-8) as an indicator of intestinal inflammation. Deoxynivalenol was the only mycotoxin able to directly increase IL-8 secretion (10- to 15-fold increase). We also investigated if these mycotoxins could indirectly stimulate IL-8 secretion through: (i) a modulation of the action of pro-inflammatory molecules such as the interleukin-1beta (IL-1β), and/or (ii) an increase in the transepithelial passage of non-invasive commensal Escherichia coli. We found that deoxynivalenol, ochratoxin A and patulin all potentiated the effect of IL-1β on IL-8 secretion (ranging from 35% to 138% increase) and increased the transepithelial passage of commensal bacteria (ranging from 12- to 1544-fold increase). In addition to potentially exacerbate established intestinal inflammation, these mycotoxins may thus participate in the induction of sepsis and intestinal inflammation in vivo. Taken together, our results suggest that the pro-inflammatory activity of enteropathogenic mycotoxins is mediated by both direct and indirect effects

  9. Gastrointestinal Headache; a Narrative Review

    Directory of Open Access Journals (Sweden)

    Majid T Noghani

    2016-08-01

    Full Text Available There are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report resolution of headache following the treatment of the associated gastrointestinal disorder. Headache disorders are classified by The International Headache Society as primary or secondary; however, among the secondary headaches, those attributed to gastrointestinal disorders are not appreciated. Therefore, we aimed to review the literature to provide evidence for headaches, which originate from the gastrointestinal system. Gastrointestinal disorders that are reported to be associated with primary headaches include dyspepsia, gastro esophageal reflux disease (GERD, constipation, functional abdominal pain, inflammatory bowel syndrome (IBS, inflammatory bowel disorders (IBD, celiac disease, and helicobacter pylori (H. Pylori infection. Some studies have demonstrated remission or improvement of headache following the treatment of the accompanying gastrointestinal disorders. Hypotheses explaining this association are considered to be central sensitization and parasympathetic referred pain, serotonin pathways, autonomic nervous system dysfunction, systemic vasculopathy, and food allergy. Traditional Persian physicians, namely Ebn-e-Sina (Avicenna and Râzi (Rhazes believed in a type of headache originating from disorders of the stomach and named it as an individual entity, the "Participatory Headache of Gastric Origin". We suggest providing a unique diagnostic entity for headaches coexisting with any gastrointestinal abnormality that are improved or cured along with the treatment of the gastrointestinal disorder.

  10. Gastrointestinal helminths in raccoons in Texas.

    Science.gov (United States)

    Kresta, Amy E; Henke, Scott E; Pence, Danny B

    2009-01-01

    Raccoons (n=590) were collected from October 1999 to August 2003 from 35 counties across Texas, and gastrointestinal tracts were examined for helminth parasites. Prevalence was calculated and differences in mean abundance were examined among habitat ecoregions, age classes, and between sexes. Twenty different species of helminths (13 nematodes, two cestodes, two acanthocephalans, and three trematodes) were positively identified in the gastrointestinal tracts of 590 raccoons in Texas. Five of the 20 helminth species collected (Physaloptera rara, Placoconus lotoris, Molineus barbatus, Atriotaenia procyonis, and Macracanthorhynchus ingens) had a prevalence >20%. The total number of individuals of these five species (n=22,777) accounted for over 86% of the total number of individuals of all helminth species (n=26,426) collected. Subsequent analyses were based on these five helminths. Mean abundance differed among habitat ecoregions, age classes, and between sexes for all five parasites evaluated. This study is the most comprehensive statewide survey ever done of gastrointestinal helminths of raccoons across Texas. The five most prevalent helminths identified have all been reported in at least one previous survey, indicating that these parasites are not new to Texas and that raccoons are not naïve to the effects these parasites have on them. It may be helpful to wildlife rehabilitators, trappers, wildlife biologists, and other professionals to be aware of parasite abundance in raccoons from different areas of the state, as frequent human-raccoon interactions occur, and some of these parasites could be harmful to humans and domestic animals.

  11. EP3 receptors inhibit antidiuretic-hormone-dependent sodium transport across frog skin epithelium

    DEFF Research Database (Denmark)

    Rytved, Klaus A.; Nielsen, Robert

    1999-01-01

    Antidiuretic hormone; tight epithelium; prostaglandin receptors; sulprostone; misoprostol; cAMP; cellular Ca2+......Antidiuretic hormone; tight epithelium; prostaglandin receptors; sulprostone; misoprostol; cAMP; cellular Ca2+...

  12. Scintigraphic assessment of gastrointestinal motility

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård

    2014-01-01

    intestinal and colonic transit. This article reviews current imaging techniques, methods for data processing and principles for evaluating results when scintigraphy is used to assess gastrointestinal motility. Furthermore, clinical indications for performing scintigraphy are reviewed.......Gastrointestinal transit reflects overall gastrointestinal motor activity and is regulated by a complex interplay between neural and hormonal stimuli. Thus, transit measurements provide a measure of the combined effects of gastrointestinal muscular activity and feedback from the gut and brain....... Dysmotility in the different major segments of the gastrointestinal tract may give rise to similar symptoms; hence, localizing transit abnormalities to a specific segment is a valuable element of diagnostic evaluation. Scintigraphy is an effective noninvasive tool to assess gastric emptying as well as small...

  13. The gastrointestinal tract

    DEFF Research Database (Denmark)

    Bartels, Else M.; Harrison, Adrian Paul

    2009-01-01

    The gastrointestinal tract (GIT) has always been and remains a major source of interest in terms of both its function, and its malfunction. Our current knowledge of age-related changes in this system, as well as drug-food interactions, however, remains relatively limited. Paradoxically, the GIT......-related GIT damage and dysfunction. New and novel aspects of drug delivery and drug-dietary supplement interactions are discusses and much needed areas of focus in terms of drug GIT testing are identified....... is not one of the core battery of tests that pharmaceutical companies are obliged to investigate as part of drug development. This review aims to cover the basics of GIT function before highlighting aspects of relevance for safety pharmacology in terms of age, cancerogenesis, and noth drug and diet...

  14. Gastrointestinal infections in children.

    Science.gov (United States)

    Mönkemüller, K E; Wilcox, C M

    2001-01-01

    Gastrointestinal infections in children are a major cause of morbidity and mortality worldwide. Children living in developing countries are particularly susceptible to infectious diarrhea because of poor standards of hygiene and sanitation. Although the magnitude of diarrheal illnesses in developed countries is less, costly hospital admissions are still frequent. The causal agent of infectious diarrhea is most frequently related to age, geographical location, lifestyle habits, use of antibiotics, associated medical conditions, social circumstances, and degree of immune competence. In this article we present some of the most important articles published in the field during the last year. The role of Helicobacter pylori in the pathogenesis of gastritis and peptic ulcer disease has been shown in adults and children. Information about the natural history of H. pylori, symptomatology, and diagnostic therapeutic approaches for children are being generated constantly; we discuss some of the most relevant information in this review.

  15. Estrogen and gastrointestinal malignancy.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    The concept that E2 exerts an effect on the gastrointestinal tract is not new and its actions on intestinal mucosa have been investigated for at least three decades. An attempt to consolidate results of these investigations generates more questions than answers, thus suggesting that many unexplored avenues remain and that the full capabilities of this steroid hormone are far from understood. Evidence of its role in esophageal, gastric and gallbladder cancers is confusing and often equivocal. The most compelling evidence regards the protective role conferred by estrogen (or perhaps ERbeta) against the development and proliferation of colon cancer. Not only has the effect been described but also many mechanisms of action have been explored. It is likely that, along with surgery, chemotherapy and radiotherapy, hormonal manipulation will play an integral role in colon cancer management in the very near future.

  16. Ultraviolet induced lysosome activity in corneal epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, A.P.

    1980-01-01

    A 5.000 W Xe-Hg high pressure lamp and a double monochromator were used to produce a 3.3 nm half-bandpass ultraviolet radiation at 295 nm. Pigmented rabbit eyes were irradiated with radiant exposures from 140 Jm/sup -2/ to 10.000 Jm/sup -2/ and evaluated by slit-lamp biomicroscopy, light and electron microscopy. Corneal threshold (Hsub(c) was 200 Jm/sup -2/ and lens threshold (Hsub(L)) was 7.500 Jm/sup -2/. The most repeatable and reliable corneal response to these levels of UV was the development of corneal epithelial granules. Histological changes included a loss of superficial epithelial cells and selective UV induced autolysis of the wing cells. It is suggested that the biomicroscopically observed granules are the clinical manifestation of the secondary lysosomes revealed by light and electron microscopy. It is proposed that UV breaks down the primary lysosome membranes to release hydrolytic enzymes which in turn form the secondary lysosomes during autolysis. Extreme levels of radiant exposure at 295 nm result in indiscriminate destruction of all layers of the corneal epithelium, but the posterior cornea was spared.

  17. Ultraviolet induced lysosome activity in corneal epithelium

    International Nuclear Information System (INIS)

    Cullen, A.P.

    1980-01-01

    A 5.000 W Xe-Hg high pressure lamp and a double monochromator were used to produce a 3.3 nm half-bandpass ultraviolet radiation at 295 nm. Pigmented rabbit eyes were irradiated with radiant exposures from 140 Jm -2 to 10.000 Jm -2 and evaluated by slit-lamp biomicroscopy, light and electron microscopy. Corneal threshold (Hsub(c) was 200 Jm -2 and lens threshold (Hsub(L)) was 7.500 Jm -2 . The most repeatable and reliable corneal response to these levels of UV was the development of corneal epithelial granules. Histological changes included a loss of superficial epithelial cells and selective UV induced autolysis of the wing cells. It is suggested that the biomicroscopically observed granules are the clinical manifestation of the secondary lysosomes revealed by light and electron microscopy. It is proposed that UV breaks down the primary lysosome membranes to release hydrolytic enzymes which in turn form the secondary lysosomes during autolysis. Extreme levels of radiant exposure at 295 nm result in indiscriminate destruction of all layers of the corneal epithelium, but the posterior cornea was spared. (orig.) [de

  18. Lower gastrointestinal malignancies

    International Nuclear Information System (INIS)

    Minsky, Bruce D.

    1995-01-01

    Objective: This refresher course will review the current knowledge as well as ongoing and future research strategies in lower gastrointestinal malignancies. Radiation therapy has a significant role in the adjuvant treatment of lower gastrointestinal malignancies. Furthermore, there are data to suggest that radiation therapy is an integral component of the conservative management (organ preservation) of rectal and anal cancers. 1. Colon cancer. The standard adjuvant treatment for node positive or high risk transmural colon cancer is postoperative 5-FU and Levamisole. There are retrospective data to suggest that certain subsets of high risk patients may benefit from postoperative radiation therapy. 2. Rectal cancer. Randomized trials have revealed an advantage of postoperative radiation therapy plus chemotherapy in transmural and/or node positive rectal cancer. In the adjuvant setting the use of continuous infusion 5-FU may be more beneficial compared with bolus 5-FU. Despite the improvement in survival, postoperative therapies are associated with an approximately 35% incidence of grade 3+ toxicity. Recent data suggest that the use of preoperative combined modality therapy may be associated with less toxicity as well as increase the chance of sphincter preservation. New Intergroup trials addressing these issues will be presented. In patients with locally advanced unresectable rectal cancer, the addition of intraoperative radiation therapy may further improve local control. 3. Anal cancer. The use of combined 5-FU/Mitomycin-C and pelvic radiation therapy is effective in the treatment of anal carcinoma. The RTOG has recently completed a randomized trial addressing the question of the effectiveness and toxicity of Mitomycin-C. The replacement Intergroup Phase III trial will be presented

  19. Stromal gastrointestinal tumors (GIST)

    International Nuclear Information System (INIS)

    Balev, B.; Boykova, K.

    2015-01-01

    Full text: GIST are a heterogeneous group of mesenchymal tumors of the gastrointestinal tract with varying tumor grade and frequency of 1: 100 000 per year. Mazur and Clark introduced the term for the first time in 1983. GIST constitute approximately 2% of the tumors in the gastrointestinal tract. The average age is 60 years. The most common locations are the stomach (60%), small intestine (30%), esophagus (1%), and rectum (5%). Learning objective: to demonstrate the imaging characteristics of the disease according to the current ESMO guidelines and to present the diagnostic accuracy of different imaging modalitiesnbased on review of literature and on own observations. GIST originate from interstitial cells (of Cajal) in the GIT wall, belonging to the autonomic nervous system, which is responsible for motility. 90% of GIST show overexpression of the KIT receptor, also known as CD117 or stem cell factor receptor. those that do not express c-KIT mutations, activate mutations in PDGFRA gene. Tumor’s macromorphology determines the imaging features on different modalities. Most of these tumors are exophytic, subepithelial, reach large size and enhance inhomogeneous due to necrosis. They usually do not cause obstruction. Ultrasound as the initiation method shows low sensitivity and specificity in GIST detection, CT with intravenous contrast is the gold standard. MRI contributes with assessing the vascularisation, cellularity and pH. FDG-PET/CT registers the metabolism of intratumoral acidosis. CT is the method of choice in the early diagnosis and determination of resectability of GIST. MRI is an additional method. PET FDG-CT is useful for the monitoring of patients treated with Imatinib

  20. Lower gastrointestinal malignancies

    International Nuclear Information System (INIS)

    Minsky, Bruce D.

    1996-01-01

    Objective: This refresher course will review the current knowledge as well as ongoing and future research strategies in lower gastrointestinal malignancies. Radiation therapy has a significant role in the adjuvant treatment of lower gastrointestinal malignancies. Furthermore, there are data to suggest that radiation therapy is an integral component of the conservative management (organ preservation) of rectal and anal cancers. 1. Colon cancer. The standard adjuvant treatment for node positive or high risk transmural colon cancer is postoperative 5-FU and Levamisole. There are retrospective data to suggest that certain subsets of high risk patients may benefit from postoperative radiation therapy. 2. Rectal cancer. Randomized trials have revealed an advantage of postoperative radiation therapy plus chemotherapy in transmural and/or node positive rectal cancer. In the adjuvant setting the use of continuous infusion 5-FU may be more beneficial compared with bolus 5-FU. Despite the improvement in survival, postoperative therapies are associated with an approximately 35% incidence of grade 3+ toxicity. Recent data suggest that the use of preoperative combined modality therapy may be associated with less toxicity as well as increase the chance of sphincter preservation. New Intergroup trials addressing these issues will be presented. In patients with locally advanced unresectable rectal cancer, the addition of intraoperative radiation therapy may further improve local control. 3. Anal cancer. The use of combined 5-FU/Mitomycin-C and pelvic radiation therapy is effective in the treatment of anal carcinoma. The RTOG has recently completed a randomized trial addressing the question of the effectiveness and toxicity of Mitomycin-C. The replacement Intergroup Phase III trial will be presented

  1. Changes in the Adult Vertebrate Auditory Sensory Epithelium After Trauma

    Science.gov (United States)

    Oesterle, Elizabeth C.

    2012-01-01

    Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells. In contrast, injured non-mammalian vertebrate ear generates replacement hair cells to restore hearing functions. Non-sensory support cells within the auditory epithelium play key roles in the repair processes. PMID:23178236

  2. Hyperplasia of epithelium adjacent to transitional cell carcinoma can be induced by growth factors through paracrine pathways

    NARCIS (Netherlands)

    W.I. de Boer (Pim); J.M.J. Rebel (Annemarie); C.D.E.M. Thijssen (C. D E M); M. Vermey; Th.H. van der Kwast (Theo); A.J.M. van den Eijnden-van Raaij (Janny)

    1994-01-01

    textabstractHyperplasia of transitional cell epithelium adjacent to human transitional cell carcinomas (TCC) is a common finding in pathology. This hyperplasia may be a precancerous aberration. Alternatively, it has been suggested that the hyperplasia is due to paracrine action of tumour-derived

  3. Impairment of vascularization of the surface covering epithelium induces ischemia and promotes malignization: a new hypothesis of a possible mechanism of cancer pathogenesis.

    Science.gov (United States)

    Karseladze, A I

    2015-06-01

    To study the peculiarities of vascularization at the stromal-epithelial interface in different types of epithelia and their alterations in precancerous lesions. Peritumoral tissues of 310 patients, tissues of 180 healthy persons and of 50 human embryos and fetuses were used. Traditional histological as well as immunohistochemical methods have been used. The study reveals that the occurrence of blood capillaries in surface squamous epithelium is an ordinary event, both in healthy persons and in peritumoral regions of the patients with squamous cell carcinoma. Glandular epithelial coverings, as well as transitional epithelium, do not contain blood vessels. In squamous epithelium, only basal cells are in contact with the membrane and underlying stroma, the cells of the upper layer receiving nutrients through diffusion. Thus, the cells of squamous epithelium are more vulnerable to blood deficiency, since for instance in the pseudo-multilayered respiratory epithelium each cell is attached directly to the basal membrane and has more ample access to the blood supply. Metaplastic squamous epithelium has a markedly reduced vascularization and seems to be more sensitive to carcinogenic stimuli. High-grade dysplastic squamous epithelium and carcinoma in situ do not contain blood vessels. The process of redistribution of vascular network occurring at the interface of epithelial-stromal frontier plays an important role in maintaining the adequate metabolism of cells including those of epithelial covering. Impairment of this mechanism most probably promotes precancerous alterations.

  4. Species variation in biology and physiology of the ciliary epithelium: similarities and differences.

    Science.gov (United States)

    Do, Chi Wai; Civan, Mortimer M

    2009-04-01

    Glaucoma is a leading cause of irreversible blindness worldwide. Lowering intraocular pressure (IOP) is the only strategy documented to delay the appearance and retard the progression of vision loss. One major approach for lowering IOP is to slow the rate of aqueous humor formation by the ciliary epithelium. As discussed in the present review, the transport basis for this secretion is largely understood. However, several substantive issues are yet to be resolved, including the integrated regulation of secretion, the functional topography of the ciliary epithelium, and the degree and significance of species variation in aqueous humor inflow. This review discusses species differences in net secretion, particularly of Cl(-) and HCO(3)(-) secretion. Identifying animal models most accurately mimicking aqueous humor formation in the human will facilitate development of future novel initiatives to lower IOP.

  5. Cellular and Molecular Mechanisms of 3,3′-Diindolylmethane in Gastrointestinal Cancer

    Directory of Open Access Journals (Sweden)

    Soo Mi Kim

    2016-07-01

    Full Text Available Studies in humans have shown that 3,3′-diindolylmethane (DIM, which is found in cruciferous vegetables, such as cabbage and broccoli, is effective in the attenuation of gastrointestinal cancers. This review presents the latest findings on the use, targets, and modes of action of DIM for the treatment of human gastrointestinal cancers. DIM acts upon several cellular and molecular processes in gastrointestinal cancer cells, including apoptosis, autophagy, invasion, cell cycle regulation, metastasis, angiogenesis, and endoplasmic reticulum (ER stress. In addition, DIM increases the efficacy of other drugs or therapeutic chemicals when used in combinatorial treatment for gastrointestinal cancer. The studies to date offer strong evidence to support the use of DIM as an anticancer and therapeutic agent for gastrointestinal cancer. Therefore, this review provides a comprehensive understanding of the preventive and therapeutic properties of DIM in addition to its different perspective on the safety of DIM in clinical applications for the treatment of gastrointestinal cancers.

  6. Regulation of Tight Junctions in Upper Airway Epithelium

    Directory of Open Access Journals (Sweden)

    Takashi Kojima

    2013-01-01

    Full Text Available The mucosal barrier of the upper respiratory tract including the nasal cavity, which is the first site of exposure to inhaled antigens, plays an important role in host defense in terms of innate immunity and is regulated in large part by tight junctions of epithelial cells. Tight junction molecules are expressed in both M cells and dendritic cells as well as epithelial cells of upper airway. Various antigens are sampled, transported, and released to lymphocytes through the cells in nasal mucosa while they maintain the integrity of the barrier. Expression of tight junction molecules and the barrier function in normal human nasal epithelial cells (HNECs are affected by various stimuli including growth factor, TLR ligand, and cytokine. In addition, epithelial-derived thymic stromal lymphopoietin (TSLP, which is a master switch for allergic inflammatory diseases including allergic rhinitis, enhances the barrier function together with an increase of tight junction molecules in HNECs. Furthermore, respiratory syncytial virus infection in HNECs in vitro induces expression of tight junction molecules and the barrier function together with proinflammatory cytokine release. This paper summarizes the recent progress in our understanding of the regulation of tight junctions in the upper airway epithelium under normal, allergic, and RSV-infected conditions.

  7. Microrobotics for future gastrointestinal endoscopy.

    Science.gov (United States)

    Menciassi, Arianna; Quirini, Marco; Dario, Paolo

    2007-01-01

    The impulse given by robotic technologies and imaging techniques to the development of a new way to conceive and perform surgery is clearly visible. Nowadays, minimally invasive surgical (MIS) procedures are often performed with the assistance of robots, such as the Da Vinci master-slave system, the AESOP robot with voice control, etc. In addition, mechatronic technologies are becoming the elective technologies for designing advanced hand-held surgical tools. The introduction of robotic technologies in endoscopy has been slower than in MIS, since the development of miniaturized robotic components for entering the small orifices of the human body is difficult. On the other hand, the large contribution that robotic technologies could bring to endoluminal techniques has been evident since the first development of instrumented catheters. In the 1990s, there was an increasing activity in the application of robotic technologies to improve endoscopic procedures in the gastrointestinal tract. The objective of robotic colonoscopy and gastroscopy was to obtain more effective diagnoses in terms of reduced pain for the patients, and to make uniform the diagnostic procedures, which too often depended on the manual abilities of the endoscopist. Currently, the availability of more reliable robotic technologies for miniaturization of size and integration of functions has allowed to conceive and develop robotic pills for the early screening of the digestive tract, with dramatic potential advantages for patients, endoscopists, and healthcare system.

  8. Expression pattern of adhesion molecules in junctional epithelium differs from that in other gingival epithelia.

    Science.gov (United States)

    Hatakeyama, S; Yaegashi, T; Oikawa, Y; Fujiwara, H; Mikami, T; Takeda, Y; Satoh, M

    2006-08-01

    The gingival epithelium is the physiologically important interface between the bacterially colonized gingival sulcus and periodontal soft and mineralized connective tissues, requiring protection from exposure to bacteria and their products. However, of the three epithelia comprising the gingival epithelium, the junctional epithelium has much wider intercellular spaces than the sulcular epithelium and oral gingival epithelium. Hence, the aim of the present study was to characterize the cell adhesion structure in the junctional epithelium compared with the other two epithelia. Gingival epithelia excised at therapeutic flap surgery from patients with periodontitis were examined for expression of adhesion molecules by immunofluorescence. In the oral gingival epithelium and sulcular epithelium, but not in the junctional epithelium, desmoglein 1 and 2 in cell-cell contact sites were more abundant in the upper than the suprabasal layers. E-cadherin, the main transmembranous molecule of adherens junctions, was present in spinous layers of the oral gingival epithelium and sulcular epithelium, but was scarce in the junctional epithelium. In contrast, desmoglein 3 and P-cadherin were present in all layers of the junctional epithelium as well as the oral gingival epithelium and sulcular epithelium. Connexin 43 was clearly localized to spinous layers of the oral gingival epithelium, sulcular epithelium and parts of the junctional epithelium. Claudin-1 and occludin were expressed in the cell membranes of a few superficial layers of the oral gingival epithelium. These findings indicated that the junctional epithelium contains only a few desmosomes, composed of only desmoglein 3; adherens junctions are probably absent because of defective E-cadherin. Thus, the anchoring junctions connecting junctional epithelium cells are lax, causing widened intercellular spaces. In contrast, the oral gingival epithelium, which has a few tight junctions, functions as a barrier.

  9. Buccal Epithelium in treating Ocular Surface Disorders

    Directory of Open Access Journals (Sweden)

    Srinivas KR

    2008-11-01

    Full Text Available Background - Ocular surface disorders due to limbal stem cell deficiency are an important cause of ocular morbidity and visual loss. Although autologous limbal stem cell transplants have helped in the management of unilateral disease, allografts in those with bilateral disease often fail due to immunological reasons. The use of autologous buccal epithelium cultivated on amniotic membrane has been described as a useful approach in the management of this condition. It is the purpose of this study to explore the feasibility of using a novel thermo-gelatin polymer (TGP as a substrate to culture these cells, and to characterize them using RNA extraction and RT-PCR. Methods - Oral cheek mucosal biopsies were obtained from 5 adult patients undergoing Modified Osteo-Odonto Keratoprosthesis surgery. The specimens were transported to the laboratory in transport medium. The cells were released using enzymatic digestion and seeded in both convention culture medium and TGP. The resulting cellular growth was characterized using RNA extraction and RT-PCR. Results - Cells could be cultured from 4 of the 5 specimens. In one specimen, contamination occurred and this was discarded. In the other specimens, the cheek epithelial cells could be cultured in both the conventional culture medium and TGP, with equal ease. RT-PCR revealed the presence of K3, a marker for epithelial cells, and GAPDH indicating the presence of some adipose tissue as well. Conclusions - It is possible to culture autologous cheek mucosal epithelial cells using TGP, a synthetic scaffold, without the need for other biological substrates. Since the specimens are obtained from the oral cavity, stringent asepsis is required. Further studies are required for histopathological characterization of the cultured cells and to create a model for delivery onto the ocular surface of eyes with bilateral surface disease due to limbal stem cell deficiency.

  10. Cyclosporine a inhibits apoptosis of rat gingival epithelium.

    Science.gov (United States)

    Ma, Su; Liu, Peihong; Li, Yanwu; Hou, Lin; Chen, Li; Qin, Chunlin

    2014-08-01

    The use of cyclosporine A (CsA) induces hyperplasia of the gingival epithelium in a site-specific response manner, but the molecular mechanism via which the lesion occurs is unclear. The present research aims to investigate the site-specific effect of CsA on the apoptosis of gingival epithelium associated with gingival hyperplasia. Forty Wistar rats were divided into CsA-treated and non-treated groups. Paraffin-embedded sections of mandibular first molars were selected for hematoxylin and eosin staining, immunohistochemistry analyses of bcl-2 and caspase-3, and the staining of terminal deoxynucleotidyl transfer-mediated dUTP nick-end labeling (TUNEL). The area of the whole gingival epithelium and the length of rete pegs were measured, and the number of bcl-2- and caspase-3-positive cells in the longest rete peg were counted. The analysis of variance for factorial designs and Fisher least significant difference test for post hoc analysis were used to determine the significance levels. In CsA-treated rats, bcl-2 expression was significantly upregulated, whereas caspase-3 expression was downregulated, along with a reduced number of TUNEL-positive cells. The site-specific distribution of bcl-2 was consistent with the site-specific hyperplasia of the gingival epithelium in CsA-treated rats. CsA inhibited gingival epithelial apoptosis via the mitochondrial pathway and common pathway. The antiapoptotic protein bcl-2 might play a critical role in the pathogenesis of the site-specific hyperplasia of gingival epithelium induced by CsA. There were mechanistic differences in the regulation of apoptosis for cells in the attached gingival epithelium, free gingival epithelium, and junctional epithelium.

  11. Anti-allergic effects of a nonameric peptide isolated from the intestine gastrointestinal digests of abalone (Haliotis discus hannai) in activated HMC-1 human mast cells.

    Science.gov (United States)

    Ko, Seok-Chun; Lee, Dae-Sung; Park, Won Sun; Yoo, Jong Su; Yim, Mi-Jin; Qian, Zhong-Ji; Lee, Chang-Min; Oh, Junghwan; Jung, Won-Kyo; Choi, Il-Whan

    2016-01-01

    The aim of the present study was to examine whether the intestine gastrointestinal (GI) digests of abalone [Haliotis discus hannai (H. discus hannai)] modulate inflammatory responses and to elucidate the mechanisms involved. The GI digests of the abalone intestines were fractionated into fractions I (>10 kDa), II (5-10 kDa) and Ⅲ (abalone intestine GI digests (AIGIDs), fraction Ⅲ inhibited the passive cutaneous anaphylaxis (PCA) reaction in mice. Subsequently, a bioactive peptide [abalone intestine GI digest peptide (AIGIDP)] isolated from fraction Ⅲ was determined to be 1175.2 Da, and the amino acid sequence was found to be PFNQGTFAS. We noted that the purified nonameric peptide (AIGIDP) attenuated the phorbol‑12‑myristate 13-acetate plus calcium ionophore A23187 (PMACI)-induced histamine release and the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in human mast cells (HMC-1 cells). In addition, we also noted that AIGIDP inhibited the PMACI‑induced activation of nuclear factor‑κB (NF-κB) by suppressing IκBα phosphorylation and that it suppressed the production of cytokines by decreasing the phosphorylation of JNK. The findings of our study indicate that AIGIDP exerts a modulatory, anti-allergic effect on mast cell-mediated inflammatory diseases.

  12. A randomized, placebo-controlled, crossover, double-blind trial of the NK1 receptor antagonist aprepitant on gastrointestinal motor function in healthy humans

    DEFF Research Database (Denmark)

    Fuglsang, S.; Madsen, Jan Lysgård

    2008-01-01

    emptying, small intestinal transit and colonic transit of a radiolabelled, 1600-kJ mixed liquid and solid meal ingested on day 2. RESULTS: Aprepitant did not change gastric retention at 15 min, gastric half emptying time, gastric mean transit time, time to small intestinal transit of 10%, small intestinal...... in healthy humans. METHODS: Twelve healthy volunteers participated in a crossover, double-blind study. In random order, each volunteer had a 125-mg capsule of aprepitant or placebo on day 1 followed by an 80-mg capsule of aprepitant or placebo on days 2-5. Gamma camera imaging was used to measure gastric...

  13. Gastrointestinal nuclear medicine

    International Nuclear Information System (INIS)

    Koblik, P.D.; Hornof, W.J.

    1985-01-01

    General localization of gastrointestinal bleeding through the use of labeled red blood cells may be performed in children, or (99m)Tc-pertechnetate may be used if a Meckel's diverticulum is suspected. As in adults, cholecystitis and biliary leak may be assessed in children via (99m)Tc-IDA derivatives. Gastroesophageal reflux can be evaluated by oral consumption of the child's usual diet labeled with (99m)Tc sulfur colloid. For the scintigraphic determination of pulmonary aspiration, a relatively high concentration of tracer within a drop of liquid is placed beneath the child's tongue followed by dynamic imaging of the respiratory tract. Colonic transit scintigraphy can aid in the identification and therapeutic decision-making in patients with functional fecal retention, the most common cause of chronic constipation in children. (18)F-DOPA positron emission tomography is useful for classifying pancreatic involvement in infantile hyperinsulinism as focal or diffuse, thereby differentiating between patients who should receive curative focal pancreatic resection versus those who should receive medical management. Assessment of protein-losing enteropathy can be conducted scintigraphically and, compared with fecal alpha-1 antitrypsin collection, the scintigraphic method can detect esophageal and gastric protein loss. Also, scintigraphic quantification of protein loss can be performed without the requirement for fecal collection. Intestinal inflammation in children with inflammatory bowel disease can be evaluated using (99m)Tc white blood cells. The scintigraphic method is safe, accurate, well-tolerated by children and complementary to endoscopy in most patients

  14. Gastrointestinal scanning agent

    International Nuclear Information System (INIS)

    Francis, M.D.

    1980-01-01

    An easily prepared radiolabeled gastrointestinal scanning agent is described. Technetium-99m has ideal characteristics for imaging the upper and lower GI tract and determining stomach emptying and intestinal transit time when used with an insoluble particulate material. For example, crystalline and amorphous calcium phosphate particles can be effectively labeled in a one-step process using sup(99m)TcO 4 and SnCl 2 . These labeled particles have insignificant mass and when administered orally pass through the GI tract unchanged, without affecting the handling and density of the intestinal contents. Visualization of the esophageal entry into the stomach, the greater and lesser curvatures of the stomach, ejection into the duodenum, and rates of passage through the upper and lower GI tract are obtained. The slurry of sup(99m)TC particulate can be given rectally by enema. Good images of the cecum and the ascending, transverse, and descending colon are obtained. Mucosal folds and the splenic and hepatic flexures are visualized. The resilience of the large intestine is also readily visualized by pneumocolonographic techniques. (author)

  15. Scintigraphic evaluation of gastrointestinal bleeding

    International Nuclear Information System (INIS)

    Park, Yong Tai; Lee, Choon Keun; Lee, Sun Wha; Choi, Woo Suk; Yoon, Yup; Lim, Jae Hoon

    1988-01-01

    Gastrointestinal bleeding remains a major diagnostic problem. Although advances have been made in the medical and surgical methods of managing gastrointestinal bleeding, the commonly employed techniques of barium radiography, endoscopy, and angiography may not successfully localize the site and define the cause of gastrointestinal bleeding. Two widely available technetium-99m-labeled radiopharmaceuticals, sulfur colloid and red blood cells are currently used in the evaluation of patients who are bleeding from the gastrointestinal tract. Surgically confirmed 19 patients with use of 99m Tc-sulfur colloid (7 cases) and 99m Tc-RBC (12 cases) were retrospectively evaluated. The overall sensitivity of scintigraphy in detection of bleeding and localization of bleeding site was 68% and 84%, respectively. The authors conclude that bleeding scintigraphy is a safe, sensitive, and non-invasive method as an effective screening test before performing angiography or surgery.

  16. Sleep Dysfunction and Gastrointestinal Diseases.

    Science.gov (United States)

    Khanijow, Vikesh; Prakash, Pia; Emsellem, Helene A; Borum, Marie L; Doman, David B

    2015-12-01

    Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases.

  17. Radiological Atlas of Gastrointestinal Disease

    International Nuclear Information System (INIS)

    Nolan, D.J.

    1983-01-01

    This book is a reference to gastrointestinal disease and radiographic methods. It provides complete information for diagnosis and management and includes coverage of plain radiography, barium studies, water-soluble contrast studies, and more

  18. GASTROINTESTINAL INJURIES FROM BLUNT ABDOMINAL ...

    African Journals Online (AJOL)

    hi-tech

    2004-04-04

    Apr 4, 2004 ... Subjects: Twenty one children managed for gastrointestinal injuries from blunt trauma ... ileus, urinary tract infection and chest infection, respectively postoperatively. .... predictive value with CT scan, (9) the positive predictive.

  19. CT of acute gastrointestinal disease

    International Nuclear Information System (INIS)

    Wittenberg, J.

    1991-01-01

    The application of computerized tomography in gastrointestinal tract diseases are presented, including advantages in surgical belly that are: anatomic clarity, wide survey and rapid performance. (C.G.C.)

  20. Antioxidant capacity of broccoli sprouts subjected to gastrointestinal digestion.

    Science.gov (United States)

    Rychlik, Joanna; Olejnik, Anna; Olkowicz, Mariola; Kowalska, Katarzyna; Juzwa, Wojciech; Myszka, Kamila; Dembczyński, Radosław; Moyer, Mary Pat; Grajek, Włodzimierz

    2015-07-01

    Broccoli is a common vegetable recognized as a rich source of antioxidants. To date, research on the antioxidant properties of broccoli, predominantly conducted on extracts, has not considered the lesions of composition and this activity after gastrointestinal digestion. Here the stability of antioxidants during gastrointestinal digestion was evaluated in conjunction with the protective effects of broccoli sprouts (BS) against oxidative stress in human colon cells. The obtained data suggest that, among the biocompounds identified in BS, glucosinolates were mainly degraded under gastrointestinal digestion, while phenolics, particularly hydroxycinnamic acid derivatives, were the most resistant constituents. The antioxidant capacity of BS extract subjected to gastrointestinal digestion was similar to or higher than that determined for non-digested BS. Gastrointestinal digested BS extract exhibited reactive oxygen species (ROS)-inhibitory capacity in NCM460 human colon cells, with 1 mg mL(-1) showing an ROS clearance of 76.59%. A 57.33% reduction in oxidative DNA damage in NCM460 cells due to treatment with digested BS extract was observed. The results lend support to the possible application of BS as a rich source of antioxidants to improve the defensive system against oxidative stress in the human colon mucosa. © 2014 Society of Chemical Industry.

  1. Transcellular sodium transport in cultured cystic fibrosis human nasal epithelium

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Boucher, Richard C.

    1991-01-01

    Cystic fibrosis (CF) airway epithelia exhibit raised transepithelial Na+ transport rates, as determined by open-circuit isotope fluxes and estimates of the amiloride-sensitive equivalent short-circuit current (Ieq). To study the contribution of apical and basolateral membrane paths to raised Na+ ...

  2. Dietary fibers from mushroom Sclerotia: 2. In vitro mineral binding capacity under sequential simulated physiological conditions of the human gastrointestinal tract.

    Science.gov (United States)

    Wong, Ka-Hing; Cheung, Peter C K

    2005-11-30

    The in vitro mineral binding capacity of three novel dietary fibers (DFs) prepared from mushroom sclerotia, namely, Pleurotus tuber-regium, Polyporous rhinocerus, and Wolfiporia cocos, to Ca, Mg, Cu, Fe, and Zn under sequential simulated physiological conditions of the human stomach, small intestine, and colon was investigated and compared. Apart from releasing most of their endogenous Ca (ranged from 96.9 to 97.9% removal) and Mg (ranged from 95.9 to 96.7% removal), simulated physiological conditions of the stomach also attenuated the possible adverse binding effect of the three sclerotial DFs to the exogenous minerals by lowering their cation-exchange capacity (ranged from 20.8 to 32.3%) and removing a substantial amount of their potential mineral chelators including protein (ranged from 16.2 to 37.8%) and phytate (ranged from 58.5 to 64.2%). The in vitro mineral binding capacity of the three sclerotial DF under simulated physiological conditions of small intestine was found to be low, especially for Ca (ranged from 4.79 to 5.91% binding) and Mg (ranged from 3.16 to 4.18% binding), and was highly correlated (r > 0.97) with their residual protein contents. Under simulated physiological conditions of the colon with slightly acidic pH (5.80), only bound Ca was readily released (ranged from 34.2 to 72.3% releasing) from the three sclerotial DFs, and their potential enhancing effect on passive Ca absorption in the human large intestine was also discussed.

  3. The impact of reduced gastric acid secretion on dissolution of salts of weak bases in the fasted upper gastrointestinal lumen: Data in biorelevant media and in human aspirates.

    Science.gov (United States)

    Litou, Chara; Vertzoni, Maria; Xu, Wei; Kesisoglou, Filippos; Reppas, Christos

    2017-06-01

    To propose media for simulating the intragastric environment under reduced gastric acid secretion in the fasted state at three levels of simulation of the gastric environment and evaluate their usefulness in evaluating the intragastric dissolution of salts of weak bases. To evaluate the importance of bicarbonate buffer in biorelevant in vitro dissolution testing when using Level II biorelevant media simulating the environment in the fasted upper small intestine, regardless of gastric acid secretions. Media for simulating the hypochlorhydric and achlorhydric conditions in stomach were proposed using phosphates, maleates and bicarbonates buffers. The impact of bicarbonates in Level II biorelevant media simulating the environment in upper small intestine was evaluated so that pH and bulk buffer capacity were maintained. Dissolution data were collected using two model compounds, pioglitazone hydrochloride and semifumarate cocrystal of Compound B, and the mini-paddle dissolution apparatus in biorelevant media and in human aspirates. Simulated gastric fluids proposed in this study were in line with pH, buffer capacity, pepsin content, total bile salt/lecithin content and osmolality of the fasted stomach under partial and under complete inhibition of gastric acid secretion. Fluids simulating the conditions under partial inhibition of acid secretion were useful in simulating concentrations of both model compounds in gastric aspirates. Bicarbonates in Level III biorelevant gastric media and in Level II biorelevant media simulating the composition in the upper intestinal lumen did not improve simulation of concentrations in human aspirates. Level III biorelevant media for simulating the intragastric environment under hypochlorhydric conditions were proposed and their usefulness in the evaluation of concentrations of two model salts of weak bases in gastric aspirates was shown. Level II biorelevant media for simulating the environment in upper intestinal lumen led to

  4. Drug therapy for gastrointestinal and liver diseases

    National Research Council Canada - National Science Library

    Ballinger, Anne; Farthing, M. J. G. (Michael J. G.)

    2001-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Gastrointestinal bleeding Matthew R Banks, Peter D Fairclough . . . . . . . . . . . . . . . . . . . . 63 Inflammatory bowel...

  5. Antioxidant supplements for preventing gastrointestinal cancers

    DEFF Research Database (Denmark)

    Bjelakovic, G; Nikolova, D; Simonetti, R G

    2004-01-01

    Oxidative stress may cause gastrointestinal cancers. The evidence on whether antioxidant supplements are effective in preventing gastrointestinal cancers is contradictory.......Oxidative stress may cause gastrointestinal cancers. The evidence on whether antioxidant supplements are effective in preventing gastrointestinal cancers is contradictory....

  6. Foreign bodies in gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Ayşe Kefeli

    2014-03-01

    Full Text Available Objective: Ingested foreign bodies in gastrointestinal tract are a common event which can cause serious morbidity and mortality in the children and adult population. For this reason, early diagnosis and treatment are crucial for preventing these life threatening complications. In this study, we aimed to analyze the characteristics of the patients with upper gastrointestinal foreign bodies that were treated in our department. Methods: Patients diagnosed with upper gastrointestinal foreign bodies who were admitted to our hospital between February 2010 and August2013 were evaluated retrospectively. The data regarding their age, gender, clinical profile, type and localization of the esophageal foreign body, performed endoscopic procedure and initial symptoms of the patients were noted and analyzed statistically. Results: Thirty-eight patients with a diagnosis of gastrointestinal foreign body were included in this study. Of these patients, 21 were male and 17 were female. The youngest patient was 17 years old and the oldest patient was 79 years old. Most of the foreign bodies (%55.3 detected in the stomach. Food waste and metallic objects in 21 and 16 patients respectively. The most common complaint was dysphagia (%50. After endoscopic intervention three of the patients were directed to surgery. Conclusion: Early recognition and treatment of gastrointestinal foreign bodies is important as their complications are life threatening. The best method of removal of foreign bodies is controversial. Early management with upper gastrointestinal endoscopy is the most efficient and safe treatment method in current conditions.

  7. Cellular distribution and function of ion channels involved in transport processes in rat tracheal epithelium.

    Science.gov (United States)

    Hahn, Anne; Faulhaber, Johannes; Srisawang, Lalita; Stortz, Andreas; Salomon, Johanna J; Mall, Marcus A; Frings, Stephan; Möhrlen, Frank

    2017-06-01

    Transport of water and electrolytes in airway epithelia involves chloride-selective ion channels, which are controlled either by cytosolic Ca 2+ or by cAMP The contributions of the two pathways to chloride transport differ among vertebrate species. Because rats are becoming more important as animal model for cystic fibrosis, we have examined how Ca 2+ - dependent and cAMP- dependent Cl - secretion is organized in the rat tracheal epithelium. We examined the expression of the Ca 2+ -gated Cl - channel anoctamin 1 (ANO1), the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel, the epithelial Na + channel ENaC, and the water channel aquaporin 5 (AQP5) in rat tracheal epithelium. The contribution of ANO1 channels to nucleotide-stimulated Cl - secretion was determined using the channel blocker Ani9 in short-circuit current recordings obtained from primary cultures of rat tracheal epithelial cells in Ussing chambers. We found that ANO1, CFTR and AQP5 proteins were expressed in nonciliated cells of the tracheal epithelium, whereas ENaC was expressed in ciliated cells. Among nonciliated cells, ANO1 occurred together with CFTR and Muc5b and, in addition, in a different cell type without CFTR and Muc5b. Bioelectrical studies with the ANO1-blocker Ani9 indicated that ANO1 mediated the secretory response to the nucleotide uridine-5'-triphosphate. Our data demonstrate that, in rat tracheal epithelium, Cl - secretion and Na + absorption are routed through different cell types, and that ANO1 channels form the molecular basis of Ca 2+ -dependent Cl - secretion in this tissue. These characteristic features of Cl - -dependent secretion reveal similarities and distinct differences to secretory processes in human airways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  8. Hair cell regeneration in the avian auditory epithelium.

    Science.gov (United States)

    Stone, Jennifer S; Cotanche, Douglas A

    2007-01-01

    Regeneration of sensory hair cells in the mature avian inner ear was first described just over 20 years ago. Since then, it has been shown that many other non-mammalian species either continually produce new hair cells or regenerate them in response to trauma. However, mammals exhibit limited hair cell regeneration, particularly in the auditory epithelium. In birds and other non-mammals, regenerated hair cells arise from adjacent non-sensory (supporting) cells. Hair cell regeneration was initially described as a proliferative response whereby supporting cells re-enter the mitotic cycle, forming daughter cells that differentiate into either hair cells or supporting cells and thereby restore cytoarchitecture and function in the sensory epithelium. However, further analyses of the avian auditory epithelium (and amphibian vestibular epithelium) revealed a second regenerative mechanism, direct transdifferentiation, during which supporting cells change their gene expression and convert into hair cells without dividing. In the chicken auditory epithelium, these two distinct mechanisms show unique spatial and temporal patterns, suggesting they are differentially regulated. Current efforts are aimed at identifying signals that maintain supporting cells in a quiescent state or direct them to undergo direct transdifferentiation or cell division. Here, we review current knowledge about supporting cell properties and discuss candidate signaling molecules for regulating supporting cell behavior, in quiescence and after damage. While significant advances have been made in understanding regeneration in non-mammals over the last 20 years, we have yet to determine why the mammalian auditory epithelium lacks the ability to regenerate hair cells spontaneously and whether it is even capable of significant regeneration under additional circumstances. The continued study of mechanisms controlling regeneration in the avian auditory epithelium may lead to strategies for inducing

  9. Comparison of transepithelial corneal crosslinking with epithelium-off crosslinking (epithelium-off CXL in adult Pakistani population with progressive keratoconus

    Directory of Open Access Journals (Sweden)

    Bushra Akbar

    2017-01-01

    CONCLUSION: Transepithelial CXL is not recommended to be replaced completely by standard epithelium-off CXL due to continued ectatic progression in 25% of cases. However, thin corneas, unfit for standard epithelium-off CXL, can benefit from transepithelial CXL.

  10. Getting to the guts of the matter: the status and potential of 'omics' research of parasitic protists of the human gastrointestinal system.

    Science.gov (United States)

    Jex, Aaron R; Koehler, Anson V; Ansell, Brendan R; Baker, Louise; Karunajeewa, Harin; Gasser, Robin B

    2013-11-01

    Parasitic protists are a major cause of diarrhoeal illnesses in humans globally. Collectively, enteric pathogens exceed all other forms of infectious disease, in terms of their estimated global prevalence and socioeconomic impact. They have a disproportionately high impact on children in impoverished communities, leading to acute (diarrhoea, vomiting, dehydration and death) and chronic disease (malabsorption, malnutrition, physical and cognitive stunting and predisposition to chronic, non-communicable disease) consequences. However, historically, investment in research and disease control measures has been disproportionately poor, leading to their current classification as neglected pathogens. A sound understanding of their biology is essential in underpinning detection, treatment and control efforts. One major tool in rapidly improving our knowledge of these parasites is the use of biological systems, including 'omic' technologies. In recent years, these tools have shown significant success when applied to enteric protists. This review summarises much of this knowledge and highlights the significant remaining knowledge gaps. A major focus of the present review was to provide a perspective on a way forward to address these gaps using advanced biotechnologies. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  11. An immunophenotypic comparison of metanephric metaplasia of Bowman capsular epithelium with metanephric adenoma, Wilms tumor, and renal development: a case report and review of the literature.

    Science.gov (United States)

    Fischer, Edgar G; Carney, J Aidan; Anderson, Scott R; Klatt, Edward C; Lager, Donna J

    2004-06-01

    Metanephric metaplasia of the parietal epithelium of the Bowman capsule is a rare pathologic finding of unknown pathogenesis that has occurred in patients with widespread malignant neoplasms of various types. We report this finding in a 25-year-old woman with partial expression of the Carney triad who died of a disseminated gastrointestinal stromal tumor, specifically a gastric stromal sarcoma. The metaplasia involved both kidneys diffusely. It originated in the parietal epithelium of the Bowman capsule, extended into the proximal tubules, and focally surrounded the glomeruli in a semicircular manner Immunohistochemical analysis revealed that the cells of metanephric metaplasia expressed the Wilms tumor gene product, bcl-2 protein, and CD57 and cytokeratin 7 and keratin AE1/AE3 focally, but not CD56. This immunophenotype parallels that of metanephric adenoma, Wilms tumor, and nephrogenic rests and overlaps with antigen expression in certain periods of renal development.

  12. Mechanism for radiation-induced damage via TLR3 on the intestinal epithelium

    International Nuclear Information System (INIS)

    Takemura, Naoki; Uematsu, Satoshi

    2014-01-01

    When the small-intestinal epithelium is injured due to high-dose radiation exposure, radiation-induced gastrointestinal syndrome (GIS) such as absorption inhibition and intestinal bacterial infection occurs, and lead to subacute death. The authors immunologically analyzed the disease onset mechanism of GIS. In the small-intestinal mucosal epithelium, the intestinal epithelial stem cells of crypt structure and their daughter cells are renewed through proliferation and differentiation in the cycle of 3 or 4 days. When DNA is damaged by radiation, although p53 gene stops cell cycle and repairs DNA, cell death is induced if the repair is impossible. When stem cells perish, cell supply stops resulting in epithelial breakdown and fatal GIS. The authors analyzed the involvement in GIS of toll-like receptor (TLR) with the function of natural immunity, based on lethal γ-ray irradiation on KO mice and other methods. The authors found the mechanism, in which RNA that was leaked due to cell death caused by p53 gene elicits inflammation by activating TLR3, and leads to GIS through a wide range of cell death induction and stem cell extinction. The administration of a TLR3/RNA binding inhibitor before the irradiation of mice decreased crypt cell death and greatly improved survival rate. The administration one hour after the irradiation also showed improvement. The administration of the TLR3 specific inhibitor within a fixed time after the exposure is hopeful for the prevention of GIS, without affecting the DNA repair function of p53 gene. (A.O.)

  13. The effect of fiber and prebiotics on children's gastrointestinal disorders and microbiome

    NARCIS (Netherlands)

    Wegh, Carrie A. M.; Schoterman, Margriet H. C.; Vaughan, Elaine E.; Belzer, Clara; Benninga, Marc A.

    2017-01-01

    Introduction: The bacteria received upon birth are the start of colonization of the approximately 10(14) bacteria that are present in the mature human gastrointestinal tract, better known as the microbiota. The gut microbiota is implicated in gastrointestinal health, nutrient metabolism and benefits

  14. The effect of fiber and prebiotics on children’s gastrointestinal disorders and microbiome

    NARCIS (Netherlands)

    Wegh, Carrie A.M.; Schoterman, Margriet H.C.; Vaughan, Elaine E.; Belzer, Clara; Benninga, Marc A.

    2017-01-01

    Introduction: The bacteria received upon birth are the start of colonization of the approximately 1014 bacteria that are present in the mature human gastrointestinal tract, better known as the microbiota. The gut microbiota is implicated in gastrointestinal health, nutrient metabolism

  15. Increase of corneal epithelium cell radioresistance during regeneration

    International Nuclear Information System (INIS)

    Popova, M.F.; Bulyakova, N.V.; Azarova, V.S.

    1985-01-01

    A comparative study of the radiosensitivity of the normal and regenerating cornea epithelium of C 57 Bl mice was performed on the cellular level, the duration of the cell cycle being taken into account. Criteria of radiation injuries were the number of chromosome aberrations, mitotic index and duration of mitotic block. The anterior part of the head was irradiated singly with 1.75, 3.5 or 7.0 Gy and also repeatedly 3.5 + 3.5 at a 24-hours interval. The corneas were fixed 2, 4, 6, 12, 24, 48, 72 and 96 hours after irradiation. In all cases of irradiated mice the regenerating epithelium showed a shorter mitotic block and significantly lower cytogenetic injury as compared with the controls. Effects of fractionated irradiation were only shown in the regenerating epithelium. The results obtained indicate that regenerating epithelium cells of the cornea are significantly more radioresistant than normal epithelium due to activation of post-radiation recovery, and also, possibly, due to an increase in the content of endogenous radioprotectors. (author)

  16. Respiratory Epithelium Lined Cyst of the Maxilla: Differential Diagnosis

    Directory of Open Access Journals (Sweden)

    C. P. Martinelli-Kläy

    2017-01-01

    Full Text Available Maxillary cysts, including the cysts lined by respiratory epithelium, can present a diagnostic challenge. We report an unusual case of a maxillary cyst on an endodontically treated tooth #16, in which the cavity was totally lined by a respiratory epithelium. The patient, a 35-year-old male, presented with a generalized chronic periodontitis and complained of a pain in the tooth #16 region. A periodontal pocket extending to the root apices with pus coming out from the gingival was found. A combined endodontic periodontal was observed on a panoramic radiography. CBCT-scan revealed a well-circumscribed radiolucent lesion at the apices of the distobuccal root of the 16. A communication with the right maxillary sinus cavity and a maxillary and ethmoidal sinusitis were also observed. The lesion was removed and histological examination revealed a cyst lined exclusively by respiratory epithelium. Ciliated and rare mucous cells were also observed. The diagnosis could evoke a surgical ciliated cyst mimicking the radicular cyst but the patient has no previous history of trauma or surgery in the maxillofacial region. It could also be an unusual radicular cyst in which the stratified squamous epithelium was destroyed by inflammation and replaced by a respiratory epithelium of the maxillary sinus.

  17. Radiation injury of the gastrointestinal tract. Pathogenesis, protection and treatment

    International Nuclear Information System (INIS)

    Svoboda, V.; Mandel, L.

    1990-01-01

    The review deals in detail with all aspects of the gastrointestinal syndrome following irradiation with various doses. After the action of low doses, 10 to 15 Gy, a fraction of unaffected hemopoietic tissues remains preserved, and spontaneous repair of the intestinal mucosa and survival take place. In the first 24 hours after irradiation, the following symptoms appear: vomiting, anorexia, arterial pressure drop, tachycardia, blockage of gastric secretion, hyperglycemia, blockage of mitoses in the active tissues, increased secretion of urea, etc. In 24 to 72 hours after irradiation, seeming adjustment takes place and depletion of the intestinal mucosa sets in. In 72 hours, edema of the submucosa, hemorrhage and diarrhea appear and depletion of lymphatic tissues commences. The last stage is agony and death. A detailed description is given of the kinetics of the intestinal epithelium and of its changes following irradiation, changes in the resorption and in the enzymatic activity of the intestine and of infections. Changes in the bile are also described. The various methods of treating the gastrointestinal syndrome are discussed; these include a dietary regimen, hypoxia, acholia, temporary ligation of the pancreatic duct, and chemoprotection. (M.D.). 195 refs

  18. Molecular Testing for Gastrointestinal Cancer

    Directory of Open Access Journals (Sweden)

    Hye Seung Lee

    2017-03-01

    Full Text Available With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC and colorectal cancer (CRC. Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4. A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2 and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

  19. Optical modulation of transgene expression in retinal pigment epithelium

    Science.gov (United States)

    Palanker, D.; Lavinsky, D.; Chalberg, T.; Mandel, Y.; Huie, P.; Dalal, R.; Marmor, M.

    2013-03-01

    Over a million people in US alone are visually impaired due to the neovascular form of age-related macular degeneration (AMD). The current treatment is monthly intravitreal injections of a protein which inhibits Vascular Endothelial Growth Factor, thereby slowing progression of the disease. The immense financial and logistical burden of millions of intravitreal injections signifies an urgent need to develop more long-lasting and cost-effective treatments for this and other retinal diseases. Viral transfection of ocular cells allows creation of a "biofactory" that secretes therapeutic proteins. This technique has been proven successful in non-human primates, and is now being evaluated in clinical trials for wet AMD. However, there is a critical need to down-regulate gene expression in the case of total resolution of retinal condition, or if patient has adverse reaction to the trans-gene products. The site for genetic therapy of AMD and many other retinal diseases is the retinal pigment epithelium (RPE). We developed and tested in pigmented rabbits, an optical method to down-regulate transgene expression in RPE following vector delivery, without retinal damage. Microsecond exposures produced by a rapidly scanning laser vaporize melanosomes and destroy a predetermined fraction of the RPE cells selectively. RPE continuity is restored within days by migration and proliferation of adjacent RPE, but since the transgene is not integrated into the nucleus it is not replicated. Thus, the decrease in transgene expression can be precisely determined by the laser pattern density and further reduced by repeated treatment without affecting retinal structure and function.

  20. Simulated gastrointestinal conditions increase adhesion ability of Lactobacillus paracasei strains isolated from kefir to Caco-2 cells and mucin.

    Science.gov (United States)

    Bengoa, Ana Agustina; Zavala, Lucía; Carasi, Paula; Trejo, Sebastián Alejandro; Bronsoms, Silvia; Serradell, María de Los Ángeles; Garrote, Graciela Liliana; Abraham, Analía Graciela

    2018-01-01

    Gastrointestinal conditions along the digestive tract are the main stress to which probiotics administrated orally are exposed because they must survive these adverse conditions and arrive alive to the intestine. Adhesion to epithelium has been considered one of the key criteria for the characterization of probiotics because it extends their residence time in the intestine and as a consequence, can influence the health of the host by modifying the local microbiota or modulating the immune response. Nevertheless, there are very few reports on the adhesion properties to epithelium and mucus of microorganisms after passing through the gastrointestinal tract. In the present work, we evaluate the adhesion ability in vitro of L. paracasei strains isolated from kefir grains after acid and bile stress and we observed that they survive simulated gastrointestinal passage in different levels depending on the strain. L. paracasei CIDCA 8339, 83120 and 83123 were more resistant than L. paracasei CIDCA 83121 and 83124, with a higher susceptibility to simulated gastric conditions. Proteomic analysis of L. paracasei subjected to acid and bile stress revealed that most of the proteins that were positively regulated correspond to the glycolytic pathway enzymes, with an overall effect of stress on the activation of the energy source. Moreover, it is worth to remark that after gastrointestinal passage, L. paracasei strains have increased their ability to adhere to mucin and epithelial cells in vitro being this factor of relevance for maintenance of the strain in the gut environment to exert its probiotic action. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. The Immunoexpression of Glucocorticoid Receptors in Breast Carcinomas, Lactational Change, and Normal Breast Epithelium and Its Possible Role in Mammary Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Raja Alyusuf

    2017-01-01

    Full Text Available The role of estrogen and progesterone receptors in breast cancer biology is well established. In contrast, other steroid hormones are less well studied. Glucocorticoids (GCs are known to play a role in mammary development and differentiation; thus, it is of interest to attempt to delineate their immunoexpression across a spectrum of mammary epithelia. Aim. To delineate the distribution pattern of glucocorticoid receptors (GRs in malignant versus nonmalignant epithelium with particular emphasis on lactational epithelium. Materials and Methods. Immunohistochemistry (IHC for GRs was performed on archival formalin-fixed paraffin-embedded tissue blocks of 96 cases comprising 52 invasive carcinomas, 21 cases with lactational change, and 23 cases showing normal mammary tissue histology. Results. Results reveal an overexpression of GRs in mammary malignant epithelium as compared to both normal and lactational groups individually and combined. GR overexpression is significantly more pronounced in HER-2-negative cancers. Discussion. This is the first study to compare GR expression in human lactating epithelium versus malignant and normal epithelium. The article discusses the literature related to the pathobiology of GCs in the breast with special emphasis on breast cancer. Conclusion. The lactational epithelium did not show overexpression of GR, while GR was overexpressed in mammary NST (ductal carcinoma, particularly HER-2-negative cancers.

  2. Duox2-induced innate immune responses in the respiratory epithelium and intranasal delivery of Duox2 DNA using polymer that mediates immunization.

    Science.gov (United States)

    Jeon, Yung Jin; Kim, Hyun Jik

    2018-05-01

    Respiratory mucosa especially nasal epithelium is well known as the first-line barrier of air-borne pathogens. High levels of reactive oxygen species (ROS) are detected in in vitro cultured human epithelial cells and in vivo lung. With identification of NADPH oxidase (Nox) system of respiratory epithelium, the antimicrobial role of ROS has been studied. Duox2 is the most abundant Nox isoform and produces the regulated amount of ROS in respiratory epithelium. Duox2-derived ROS are involved in antiviral innate immune responses but more studies are needed to verify the mechanism. In respiratory epithelium, Duox2-derived ROS is critical for recognition of virus through families retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) at the early stage of antiviral innate immune responses. Various secreted interferons (IFNs) play essential roles for antiviral host defense by downstream cell signaling, and transcription of IFN-stimulated genes is started to suppress viral replication. Type I and type III IFNs are verified more responsible for influenza A virus (IAV) infection in respiratory epithelium and Duox2 is required to regulate IFN-related immune responses. Transient overexpression of Duox2 using cationic polymer polyethylenimine (PEI) induces secretion of type I and type III IFNs and significantly attenuated IAV replication in respiratory epithelium. Here, we discuss Duox2-mediated antiviral innate immune responses and the role of Duox2 as a mucosal vaccine to resist respiratory viral infection.

  3. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

    2016-04-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

    2010-01-01

    This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...... (SK(Ca)) and intermediate (IK(Ca))-conductance calcium-activated potassium channels, NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) was used to induce EpDHF-type relaxation. IK(Ca) and SK(Ca)3 positive immunoreactions were observed mainly in the epithelium and endothelium of bronchioles and arteries......, respectively. In 5-hydroxytryptamine (1 microM)-contracted bronchioles (828 +/- 20 microm, n = 84) and U46619 (0.03 microM)-contracted arteries (720 +/- 24 microm, n = 68), NS309 (0.001-10 microM) induced concentration-dependent relaxations that were reduced by epithelium/endothelium removal and by blocking IK...

  5. Prevalence of Spirometra and other gastrointestinal helminths in ...

    African Journals Online (AJOL)

    Dogs are domesticated by human for different purpose and perform a wide range of social, cultural, and economic functions in the society but are prone to different kinds of health problems. The objective of this study was to investigate the prevalence of Spirometra and other gastrointestinal helminths affecting dogs in ...

  6. The Impact of Opioid Treatment on Regional Gastrointestinal Transit

    DEFF Research Database (Denmark)

    Poulsen, Jakob Lykke; Nilsson, Matias; Brock, Christina

    2016-01-01

    BACKGROUND/AIMS: To employ an experimental model of opioid-induced bowel dysfunction in healthy human volunteers, and evaluate the impact ofopioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility assessed by questionnaires and regional GItransit times using the 3...

  7. Anti-angiogenic treatment of gastrointestinal malignancies.

    Science.gov (United States)

    Salmon, J Stuart; Lockhart, A Craig; Berlin, Jordan

    2005-01-01

    The scientific rationale to block angiogenesis as a treatment strategy for human cancer has been developed over the last 30 years, but is only now entering the clinical arena. Preclinical studies have demonstrated the importance of the vascular endothelial growth factor (VEGF) pathways in both physiologic and pathologic angiogenesis, and have led to the development of approaches to block its role in tumor angiogenesis. Bevacizumab is an antibody to VEGF and has been shown to prolong survival when given with chemotherapy in the treatment of metastatic colorectal cancer (CRC). Although this is the first anti-angiogenic treatment to be approved for the treatment of human epithelial malignancy, a number of other approaches currently are in development. Soluble chimeric receptors to sequester serum VEGF and monoclonal antibodies against VEGF receptors have both shown considerable promise in the laboratory and are being brought into clinical investigation. A number of small-molecule tyrosine kinase inhibitors that have activity against VEGF receptors also are in clinical trials. Although these novel treatments are being pioneered in CRC, anti-angiogenic approaches also are being tested in the treatment of other gastrointestinal malignancies. Anti-VEGF therapy has shown promise in such traditionally resistant tumors as pancreatic cancer and hepatocellular carcinoma. This review will examine the preclinical foundation and then focus on the clinical studies of anti-VEGF therapy in gastrointestinal cancers.

  8. The distribution of free calcium ions in the cholesteatoma epithelium

    DEFF Research Database (Denmark)

    Svane-Knudsen, Viggo; Rasmussen, Gurli; Ottosen, Peter D

    2005-01-01

    The distribution of free calcium ions in normal skin and cholesteatoma epithelium was investigated using the oxalate precipitation method. In agreement with previous observations, we could demonstrate a calcium ion gradient in normal epidermis where the cells in stratum basale and spinosum reside...... appeared where oblong accumulations of free calcium ions were found basally in the stratum. These findings provide evidence that fluctuations in epidermal calcium in cholesteatoma epithelium may underlie the abnormal desquamation, may contribute to the formation of an abnormal permeability barrier and may...

  9. [Characterization, influence and manipulation of the gastrointestinal microbiota in health and disease].

    Science.gov (United States)

    García-Mazcorro, José F; Garza-González, Elvira; Marroquín-Cardona, Alicia G; Tamayo, José L

    2015-01-01

    The gastrointestinal tract harbors trillions of microorganisms that are indispensable for health. The gastrointestinal microbiota can be studied using culture and molecular methods. The applications of massive sequencing are constantly increasing, due to their high yield, increasingly accessible costs, and the availability of free software for data analysis. The present article provides a detailed review of a large number of studies on the gastrointestinal microbiota and its influence on human health; particular emphasis is placed on the evidence suggesting a relationship between the gastrointestinal microbial ecosystem and diverse physiological and immune/inflammatory processes. Discussion of the articles analyzed combines a medical approach and current concepts of microbial molecular ecology. The present revision aims to be useful to those interested in the gastrointestinal microbiota and its possible alteration to maintain, re-establish and enhance health in the human host. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

  10. Cdx1 and c-Myc foster the initiation of transdifferentiation of the normal esophageal squamous epithelium toward Barrett's esophagus.

    Directory of Open Access Journals (Sweden)

    Douglas B Stairs

    Full Text Available Barrett's esophagus is a premalignant condition whereby the normal stratified squamous esophageal epithelium undergoes a transdifferentiation program resulting in a simple columnar epithelium reminiscent of the small intestine. These changes are typically associated with the stratified squamous epithelium chronically exposed to acid and bile salts as a result of gastroesophageal reflux disease (GERD. Despite this well-defined epidemiologic association between acid reflux and Barrett's esophagus, the genetic changes that induce this transdifferentiation process in esophageal keratinocytes have remained undefined.To begin to identify the genetic changes responsible for transdifferentiaiton in Barrett's esophagus, we performed a microarray analysis of normal esophageal, Barrett's esophagus and small intestinal biopsy specimens to identify candidate signaling pathways and transcription factors that may be involved. Through this screen we identified the Cdx1 homeodomain transcription factor and the c-myc pathway as possible candidates. Cdx1 and c-myc were then tested for their ability to induce transdifferentiation in immortalized human esophageal keratinocytes using organotypic culturing methods. Analyses of these cultures reveal that c-myc and cdx1 cooperate to induce mucin production and changes in keratin expression that are observed in the epithelium of Barrett's esophagus.These data demonstrate the ability of Cdx1 and c-myc to initiate the earliest stages of transdifferentiation of esophageal keratinocytes toward a cell fate characteristic of Barrett's esophagus.

  11. Functional brain imaging of gastrointestinal sensation in health and disease

    Institute of Scientific and Technical Information of China (English)

    Lukas Van Oudenhove; Steven J Coen; Qasim Aziz

    2007-01-01

    It has since long been known, from everyday experience as well as from animal and human studies, that psychological processes-both affective and cognitiveexert an influence on gastrointestinal sensorimotor function. More specifically, a link between psychological factors and visceral hypersensitivity has been suggested,mainly based on research in functional gastrointestinal disorder patients. However, until recently, the exact nature of this putative relationship remained unclear,mainly due to a lack of non-invasive methods to study the (neurobiological) mechanisms underlying this relationship in non-sleeping humans. As functional brain imaging, introduced in visceral sensory neuroscience some 10 years ago, does provide a method for in vivo study of brain-gut interactions, insight into the neurobiological mechanisms underlying visceral sensation in general and the influence of psychological factors more particularly,has rapidly grown. In this article, an overview of brain imaging evidence on gastrointestinal sensation will be given, with special emphasis on the brain mechanisms underlying the interaction between affective & cognitive processes and visceral sensation. First, the reciprocal neural pathways between the brain and the gut (braingut axis) will be briefly outlined, including brain imaging evidence in healthy volunteers. Second, functional brain imaging studies assessing the influence of psychological factors on brain processing of visceral sensation in healthy humans will be discussed in more detail.Finally, brain imaging work investigating differences in brain responses to visceral distension between healthy volunteers and functional gastrointestinal disorder patients will be highlighted.

  12. Scintigraphic evaluation of gastrointestinal motility disorders

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Jae Gol [College of Medicine, Korea Univ., Seoul (Korea, Republic of)

    2001-02-01

    Current scintigraphic tests of gastrointestinal motor function provides relevant pathophysiologic information, but their clinical utility is controversial. Many scintigraphic methods are developed to investigate gastrointestinal motility from oral cavity to colon. These are esophageal transit scintigraphy, oropharyngeal transit study, gastric emptying test, small bowel transit time measurement, colon transit study and gastroesopahgeal reflux scintigraphy. Scintigraphy of gastrointestinal tract is the most physiologic and noninvasive method to evaluate gastrointestinal motility disorders. Stomach emptying test is regarded as a gold standard in motility study. Gastrointestinal transit scintigraphy also has a certain role in assessment of drug effect to GI motility and changes after theraphy of motility disorders. Scintigraphy provides noninvasive and quantitative assessment of physiological transit throughout the gastrointestinal tract, and it is extremely useful for diagnosing gastrointestinal motor dysfunction. This article reviews the current procedures, indications, significance and guidelines for gastrointestinal motility measurements by scintigraphy.

  13. Scintigraphic evaluation of gastrointestinal motility disorders

    International Nuclear Information System (INIS)

    Choe, Jae Gol

    2001-01-01

    Current scintigraphic tests of gastrointestinal motor function provides relevant pathophysiologic information, but their clinical utility is controversial. Many scintigraphic methods are developed to investigate gastrointestinal motility from oral cavity to colon. These are esophageal transit scintigraphy, oropharyngeal transit study, gastric emptying test, small bowel transit time measurement, colon transit study and gastroesopahgeal reflux scintigraphy. Scintigraphy of gastrointestinal tract is the most physiologic and noninvasive method to evaluate gastrointestinal motility disorders. Stomach emptying test is regarded as a gold standard in motility study. Gastrointestinal transit scintigraphy also has a certain role in assessment of drug effect to GI motility and changes after theraphy of motility disorders. Scintigraphy provides noninvasive and quantitative assessment of physiological transit throughout the gastrointestinal tract, and it is extremely useful for diagnosing gastrointestinal motor dysfunction. This article reviews the current procedures, indications, significance and guidelines for gastrointestinal motility measurements by scintigraphy

  14. Gastrointestinal Carcinoid Tumors—Health Professional Version

    Science.gov (United States)

    Gastrointestinal carcinoid tumors are rare, slow-growing tumors that originate in the neuroendocrine cells in the GI tract. Find evidence-based information on gastrointestinal carcinoid tumors treatment and research.

  15. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

    International Nuclear Information System (INIS)

    Clewell, H.J.; Efremenko, A.; Campbell, J.L.; Dodd, D.E.; Thomas, R.S.

    2014-01-01

    Male and female Fischer 344 rats were exposed to naphthalene vapors at 0 (controls), 0.1, 1, 10, and 30 ppm for 6 h/d, 5 d/wk, over a 90-day period. Following exposure, the respiratory epithelium and olfactory epithelium from the nasal cavity were dissected separately, RNA was isolated, and gene expression microarray analysis was conducted. Only a few significant gene expression changes were observed in the olfactory or respiratory epithelium of either gender at the lowest concentration (0.1 ppm). At the 1.0 ppm concentration there was limited evidence of an oxidative stress response in the respiratory epithelium, but not in the olfactory epithelium. In contrast, a large number of significantly enriched cellular pathway responses were observed in both tissues at the two highest concentrations (10 and 30 ppm, which correspond to tumorigenic concentrations in the NTP bioassay). The nature of these responses supports a mode of action involving oxidative stress, inflammation and proliferation. These results are consistent with a dose-dependent transition in the mode of action for naphthalene toxicity/carcinogenicity between 1.0 and 10 ppm in the rat. In the female olfactory epithelium (the gender/site with the highest incidences of neuroblastomas in the NTP bioassay), the lowest concentration at which any signaling pathway was significantly affected, as characterized by the median pathway benchmark dose (BMD) or its 95% lower bound (BMDL) was 6.0 or 3.7 ppm, respectively, while the lowest female olfactory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 16.1, 11.1, and 8.4 ppm, respectively. In the male respiratory epithelium (the gender/site with the highest incidences of adenomas in the NTP bioassay), the lowest pathway BMD and BMDL were 0.4 and 0.3 ppm, respectively, and the lowest male respiratory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 0.5, 0.7, and 0.9 ppm

  16. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

    Energy Technology Data Exchange (ETDEWEB)

    Clewell, H.J., E-mail: hclewell@thehamner.org; Efremenko, A.; Campbell, J.L.; Dodd, D.E.; Thomas, R.S.

    2014-10-01

    Male and female Fischer 344 rats were exposed to naphthalene vapors at 0 (controls), 0.1, 1, 10, and 30 ppm for 6 h/d, 5 d/wk, over a 90-day period. Following exposure, the respiratory epithelium and olfactory epithelium from the nasal cavity were dissected separately, RNA was isolated, and gene expression microarray analysis was conducted. Only a few significant gene expression changes were observed in the olfactory or respiratory epithelium of either gender at the lowest concentration (0.1 ppm). At the 1.0 ppm concentration there was limited evidence of an oxidative stress response in the respiratory epithelium, but not in the olfactory epithelium. In contrast, a large number of significantly enriched cellular pathway responses were observed in both tissues at the two highest concentrations (10 and 30 ppm, which correspond to tumorigenic concentrations in the NTP bioassay). The nature of these responses supports a mode of action involving oxidative stress, inflammation and proliferation. These results are consistent with a dose-dependent transition in the mode of action for naphthalene toxicity/carcinogenicity between 1.0 and 10 ppm in the rat. In the female olfactory epithelium (the gender/site with the highest incidences of neuroblastomas in the NTP bioassay), the lowest concentration at which any signaling pathway was significantly affected, as characterized by the median pathway benchmark dose (BMD) or its 95% lower bound (BMDL) was 6.0 or 3.7 ppm, respectively, while the lowest female olfactory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 16.1, 11.1, and 8.4 ppm, respectively. In the male respiratory epithelium (the gender/site with the highest incidences of adenomas in the NTP bioassay), the lowest pathway BMD and BMDL were 0.4 and 0.3 ppm, respectively, and the lowest male respiratory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 0.5, 0.7, and 0.9 ppm

  17. Hedgehog Signaling and Maintenance of Homeostasis in the Intestinal Epithelium

    NARCIS (Netherlands)

    Büller, Nikè V. J. A.; Rosekrans, Sanne L.; Westerlund, Jessica; van den Brink, Gijs R.

    2012-01-01

    Homeostasis of the rapidly renewing intestinal epithelium depends on a balance between cell proliferation and loss. Indian hedgehog (Ihh) acts as a negative feedback signal in this dynamic equilibrium. We discuss recent evidence that Ihh may be one of the key epithelial signals that indicates

  18. DIFFERENTIAL HISTOMORPHOMETRIC CHANGES IN NORMAL AND INFLAMED GINGIVAL EPITHELIUM

    Directory of Open Access Journals (Sweden)

    Tanaskovic Stankovic Sanja

    2016-12-01

    Full Text Available Introduction and aim: In recent decades, many factors such as smoking, unhealthy diet as well as high alcohol intake were marked as risk factors that can lead to increased incidence of malignant alterations, gingivitis, periodontal disease and other oral epithelium pathological changes. Having in mind that in the group of non-malignant and non-dental oral pathology gingivitis and periodontal disease are the most common oral mucosa alterations aim of our research was to investigate histomorphometric characteristics of healthy and altered oral and gingival epithelium. Material and methods: Tissue samples of 24 oral and gingival mucosa specimens were collected. Samples were fixed in 10% buffered paraformaldehyde, routinely processed and embedded in paraffin blocks. From each block sections 5 micrometer thin were made and standard H/E staining as well as immunocytochemical detection of Ki-67 proliferation marker and CD79a lymphocyte marker were performed. Measurements and image analysis was performed with Image Pro Plus software (Media Cybernetics, USA and Axiovision (Ziess, USA. Results: We showed that inflamed gingival epithelium is increasing its thickness in proportion to the severity of adjacent inflammation. Furthermore, mitotic index is rising (up to 132% in the same manner as well as basal lamina length (up to 70% when normal and inflamed gingiva is compared. Architecture of epithelial ridges is changed from straightforward to mesh-like. Conclusion: Assessment of the free gingival epithelium thickness is directly related to the severity of the inflammation process i

  19. Examination of the reticular epithelium of the bovine pharyngeal tonsil

    Science.gov (United States)

    The nasopharyngeal tonsil (adenoid), located at the posterior of the nasopharynx is ideally positioned to sample antigens entering through the nasal cavity or oral cavity. Entering antigens will first contact tonsilar epithelium. To better understand the cellular composition of this important epithe...

  20. Relative permeability of the endothelium and epithelium of rabbit lungs

    International Nuclear Information System (INIS)

    Effros, R.M.; Mason, G.R.; Silverman, P.; Hukkanen, J.

    1986-01-01

    Electron micrographic studies of lungs suggest that the epithelial cells are more tightly joined than the underlying endothelium, and macromolecules penetrate the endothelium more readily than the epithelium. Comparisons of epithelial and endothelial permeability to small molecules have been based upon the relative rates at which solutes traverse the alveolar-capillary barrier in fluid filled lungs and those at which they equilibrate across the capillaries in air-filled lungs. Because the former process is much slower than the latter, it has been concluded that the epithelium is less permeable to small solutes than the endothelium. However this difference may be related to inadequate access of solutes to airway surfaces. In this study, solute losses from the vascular space were compared to those from the airspace in perfused, fluid-filled rabbit lungs. 36 Cl - and 125 I - were lost from air-spaces almost twice as rapidly as 22 Na + . In contrast, the endothelium is equally permeable to 22 Na + and these anions. Loss of 3 H-mannitol from the perfusate resembled that of 22 Na + for about 30 minutes, after which diffusion of 3 H-mannitol into the tissue nearly ceased. These observations suggest that the epithelium is more permselective than the endothelium. By resisting solute and water transport, the epithelium tends to prevent alveolar flooding and confines edema to the interstitium, where it is less likely to interfere with gas exchange

  1. Wnt signaling in the intestinal epithelium: from endoderm to cancer.

    NARCIS (Netherlands)

    Gregorieff, A.; Clevers, J.C.

    2005-01-01

    The Wnt pathway controls cell fate during embryonic development. It also persists as a key regulator of homeostasis in adult self-renewing tissues. In these tissues, mutational deregulation of the Wnt cascade is closely associated with malignant transformation. The intestinal epithelium represents

  2. Structure and development of the saccular sensory epithelium in ...

    African Journals Online (AJOL)

    Structure and development of the saccular sensory epithelium in relation to otolith growth in the perch Perca fluviatilis (Telostei) ... Electron microscopy indicated: 1) The apical surface of each hair cell is covered with a ciliary bundle which varies in length in different epithelial regions. Each bundle is formed from a long ...

  3. Radioautographic DNA synthesis study on mice Mus musculus gingival epithelium

    International Nuclear Information System (INIS)

    Silveira Tarelho, Z.V. da; Hetem, S.

    1984-01-01

    The DNA-synthetizing cells frequency in the gingival epithelium basal layer of the first lower molar region in young and adult mice were studied. The 3H-thymidine and radioautography were used. The labeled cells frequency was determined by calculating their proportions. The data were statiscally analysed. (M.A.C.) [pt

  4. The ultrastructure of the midgut epithelium in millipedes (Myriapoda, Diplopoda)

    Czech Academy of Sciences Publication Activity Database

    Sosinka, A.; Rost-Roszkowska, M.M.; Vilímová, J.; Tajovský, Karel; Kszuk-Jendrysik, M.; Chajec, Ł.; Sonakowska, L.; Kamińska, K.; Hyra, M.; Poprawa, I.

    2014-01-01

    Roč. 43, č. 5 (2014), s. 477-492 ISSN 1467-8039 Institutional support: RVO:60077344 Keywords : digestive cells * midgut epithelium * millipedes * regenerative cells * secretory cells * ultrastructure Subject RIV: EG - Zoology Impact factor: 1.650, year: 2014

  5. GASTROINTESTINAL FOOD ALLERGY IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Svetlana G. Makarova

    2017-01-01

    Full Text Available In recent years, there has been a significant increase in the prevalence  of food allergies. Pathological conditions associated  with a food intolerance are becoming an increasingly urgent problem of pediatrics. According to different researchers, allergic lesions of the gastrointestinal tract occurs in 25–50% of patients with such common pathology as an allergy to cow's milk proteins. The severity of diseases  associated  with food allergies and their prognosis  depend largely on early diagnosis and adequate treatment. Difficulties and errors  in the diagnosis  of gastrointestinal  food allergies  are associated  with both subjective  and objective  reasons,  primarily due to the fact that gastrointestinal  reactions to food are often delayed and non-IgE-mediated. The article describes clinical forms of gastrointestinal food allergy according to the existing classification. Diagnostic algorithms and modern approaches  to differential diagnosis of disease based on evidence-based  medicine and corresponding to international consensus papers are given.

  6. GASTROINTESTINAL TRACT OF CLARIAS GARIEPINUS ...

    African Journals Online (AJOL)

    DR. AMINU

    one hundred and ninety nine (199) were infested fish samples from gills and gastrointestinal tract .... Body cavity of fish were dissected using a pair of scissors and different portion of the gut (Oesophagus, stomach, intestine and rectum) were isolated and kept in .... Arme, C. and Wakey, M. (1970): The physiology of fishes.

  7. Nutritional management of gastrointestinal malignancies ...

    African Journals Online (AJOL)

    The evidence connecting food and gastrointestinal cancers from epidemiological studies, case-control studies, and prospective observational studies, indicates that determining the independent effects of specific nutrients is extremely diffi cult, given the many potential environmental factors to consider. The nutritional ...

  8. Approach to upper gastrointestinal bleeding

    African Journals Online (AJOL)

    Upper gastrointestinal haemorrhage has a variety of causes (Table 1) and is the commonest complication of peptic ulceration and portal hypertension. Peptic ulceration in the duo- denum or stomach and oesophageal varices are the conditions most often responsible for patients who have the potential to present.

  9. Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium.

    Science.gov (United States)

    Murata, Yoji; Kotani, Takenori; Supriatna, Yana; Kitamura, Yasuaki; Imada, Shinya; Kawahara, Kohichi; Nishio, Miki; Daniwijaya, Edwin Widyanto; Sadakata, Hisanobu; Kusakari, Shinya; Mori, Munemasa; Kanazawa, Yoshitake; Saito, Yasuyuki; Okawa, Katsuya; Takeda-Morishita, Mariko; Okazawa, Hideki; Ohnishi, Hiroshi; Azuma, Takeshi; Suzuki, Akira; Matozaki, Takashi

    2015-08-04

    Intestinal epithelial cells contribute to regulation of intestinal immunity in mammals, but the detailed molecular mechanisms of such regulation have remained largely unknown. Stomach-cancer-associated protein tyrosine phosphatase 1 (SAP-1, also known as PTPRH) is a receptor-type protein tyrosine phosphatase that is localized specifically at microvilli of the brush border in gastrointestinal epithelial cells. Here we show that SAP-1 ablation in interleukin (IL)-10-deficient mice, a model of inflammatory bowel disease, resulted in a marked increase in the severity of colitis in association with up-regulation of mRNAs for various cytokines and chemokines in the colon. Tyrosine phosphorylation of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20, an intestinal microvillus-specific transmembrane protein of the Ig superfamily, was greatly increased in the intestinal epithelium of the SAP-1-deficient animals, suggesting that this protein is a substrate for SAP-1. Tyrosine phosphorylation of CEACAM20 by the protein tyrosine kinase c-Src and the consequent association of CEACAM20 with spleen tyrosine kinase (Syk) promoted the production of IL-8 in cultured cells through the activation of nuclear factor-κB (NF-κB). In addition, SAP-1 and CEACAM20 were found to form a complex through interaction of their ectodomains. SAP-1 and CEACAM20 thus constitute a regulatory system through which the intestinal epithelium contributes to intestinal immunity.

  10. Gastrointestinal Stromal Tumors: A Case Report

    OpenAIRE

    Sashidharan, Palankezhe; Matele, Apoorva; Matele, Usha; Al Felahi, Nowfel; Kassem, Khalid F.

    2014-01-01

    Advances in the identification of gastrointestinal stromal tumors, its molecular and immunohiostochemical basis, and its management have been a watershed in the treatment of gastrointestinal tumors. This paradigm shift occurred over the last two decades and gastrointestinal stromal tumors have now come to be understood as rare gastrointestinal tract tumors with predictable behavior and outcome, replacing the older terminologies like leiomyoma, schwannoma or leiomyosarcoma. This report present...

  11. Tumor del estroma gastrointestinal Tumor of the gastrointestinal stroma

    Directory of Open Access Journals (Sweden)

    Jorge Felipe Montero León

    2012-03-01

    Full Text Available Los tumores del estroma gastrointestinal, conocidos según sus siglas en inglés como GIST (gastrointestinal stromal tumors, son tumores mesenquimales que aparecen en cualquier lugar a lo largo del tracto intestinal. Este trabajo tiene el propósito de presentar una paciente de 60 años de edad que asiste a la consulta de ginecología del Instituto Nacional de Oncología y Radiobiología, por presentar dolor en el epigastrio, que se irradia al flanco derecho, con un aumento de volumen en la fosa iliaca derecha, y por ultrasonografía se plantea un tumor de ovario derecho, que se proyecta hacia el epigastrio y a hipocondrio derecho. Se describe la intervención quirúrgica y los hallazgos encontrados en estudios macro y microscópicos, así como en estudios posteriores por inmunohistoquímica de la lesión. Se concluye con un diagnóstico de tumor del estroma gastrointestinal y los resultados de las intervenciones quirúrgicas y medicamentosas realizadas. Se recomienda valorar la importancia de una estrecha relación entre cirujanos generales y ginecólogos frente a enfermedades inesperadas, por su difícil diagnóstico preoperatorio, que conllevan a un tratamiento quirúrgico adecuado, y que por la complejidad que requieren, necesitan de la competencia de ambas especialidades quirúrgicas.The tumors of the gastrointestinal stroma, known in English language as GIST (gastrointestinal stromal tumors are mesenchymal tumors appearing in any place throughout the intestinal tract. The objective of present paper is to present the case of a female patient aged 60 came to Genecology consultation of the National Institute of Oncology and Radiobiology due pain in epigastrium irradiating to right flank with increase of volume in the right iliac fossa and by ultrasonography it is a tumor of right ovarium projecting to epigastrium and the right hypochondrium. The surgical intervention is described as well as the findings noted in macro- and microscopic studies

  12. Histomorphology of the corneal epithelium of anastrozole treated rabbits

    International Nuclear Information System (INIS)

    Khalil, A.; Qamar, K.; Butt, S.A.

    2013-01-01

    Objective: To evaluate the effects of prolonged use of anastrozole as an endocrine treatment of breast cancer on the corneal epithelium in an animal model. Study Design: Laboratory based randomized control trial. Place and Duration of Study: Department of Anatomy, Army Medical College, Rawalpindi in collaboration with National Institute of Health, Islamabad, six months from Jun 2012 to Nov 2012. Material and Methods: Twenty adult female NewZealand white rabbits were taken. Ten rabbits were placed in control group taking normal diet and 10 were given anastrozole orally in the normal dose of 1 mg/day (0.02 mg/kg/day). After the completion of the study, corneas were removed and grossly examined. The specimen were fixed and slides prepared for histomorphological examination. The epithelium in each slide was examined for any deposits, edema or increase in stratification and the height of the epithelium was measured for each eye. The results were compared between the groups for statistical significance. Results: The epithelium had normal shape with no areas of any deposits, edema or ulceration. The mean epithelial height in the control group was 21.25 +- 4.29 mu m and 21.00 +- 4.28 mu m in the right corneas and left corneas, respectively. The mean epithelial height taken from the experimental group was 20.50 +- 4.97 mu m and 21.00 +- 4.28 mu m in right sided and left sided corneas, respectively. The p value was calculated to be 0.722 and 1.00 for the right and left corneas, respectively and no statistical significance was found in between the two groups. Conclusion: Long term administration of anastrozole has no effect on the histological morphology of the corneal epithelium. (author)

  13. Kinetics of corneal epithelium turnover in vivo. Studies of lovastatin

    International Nuclear Information System (INIS)

    Cenedella, R.J.; Fleschner, C.R.

    1990-01-01

    The authors developed a direct chemical approach for estimating the rate of turnover of the corneal epithelium in vivo. The method was used to examine the effects of lovastatin, a potent inhibitor of cholesterol biosynthesis, on proliferation and turnover of the epithelium. Corneal DNA was labeled by pulse injection (IP) of the rat with 3H-thymidine, and 3H-labeled DNA was recovered from peripheral and central corneas over the next 15 days. Only the epithelium became labeled, and the loss of label by cell desquamation began 3 days after injection. The loss of 3H-DNA from the cornea (peripheral plus central region) followed first-order kinetics. The half-life of the disappearance was about 3 days. The peripheral cornea became more highly labeled than the central cornea and began to lose 3H-DNA before the central cornea. These observations support the possibility of a higher mitotic rate in the peripheral region and the centripetal movement of a population of peripheral epithelial cells in the normal cornea. The half-lives of the disappearance of 3H-DNA from peripheral and central corneas measured between days 5 and 15 postinjection were identical, both at 3 days. Complete turnover of the corneal epithelium would, therefore, require about 2 weeks (4-5 half-lives). Treatment of the rat with lovastatin had no obvious effects upon the proliferation or turnover of the corneal epithelium. Although lovastatin inhibited corneal 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key regulatory enzyme of cholesterol synthesis, the cornea compensated by induction of this enzyme so that there was no net inhibition of cholesterol synthesis in the cornea

  14. Exercise and the gastro-intestinal tract

    African Journals Online (AJOL)

    on perfonnance and me value of cardiovascular training in improving performance in aerobic sports is well recognised. The role of me gastro-intestinal tracr, bom as a limiting and sustaining facror in aerobic exercises, is less well appreciared. Gastro-intestinal symptoms. The spectrum of gastro-intestinal effecrs of exercise ...

  15. Ultrastructural Histopathology of Vervet Monkey Colonic Epithelium After In Vitro Exposure to Cell-free Supernatants of Shigella Cultures

    OpenAIRE

    Hill, R. R.; Collins, N. E.; Cowley, H. M.

    2011-01-01

    The full dysentery syndrome of human shigellosis is often preceded by a transient diarrhoea that may be induced by bacterial extracellular products before invasion of the colonic mucosa and development of subsequent pathology. To examine this hypothesis, we studied the effects of cell-free cultures of Shigella sp. on the ultrastructure of monkey colonic epithelium in vitro. Clinical isolates of shigella strains were grown in a niche-simulating medium. Sheets of colon wall collected from verve...

  16. Virtual reality simulators for gastrointestinal endoscopy training.

    Science.gov (United States)

    Triantafyllou, Konstantinos; Lazaridis, Lazaros Dimitrios; Dimitriadis, George D

    2014-01-16

    The use of simulators as educational tools for medical procedures is spreading rapidly and many efforts have been made for their implementation in gastrointestinal endoscopy training. Endoscopy simulation training has been suggested for ascertaining patient safety while positively influencing the trainees' learning curve. Virtual simulators are the most promising tool among all available types of simulators. These integrated modalities offer a human-like endoscopy experience by combining virtual images of the gastrointestinal tract and haptic realism with using a customized endoscope. From their first steps in the 1980s until today, research involving virtual endoscopic simulators can be divided in two categories: investigation of the impact of virtual simulator training in acquiring endoscopy skills and measuring competence. Emphasis should also be given to the financial impact of their implementation in endoscopy, including the cost of these state-of-the-art simulators and the potential economic benefits from their usage. Advances in technology will contribute to the upgrade of existing models and the development of new ones; while further research should be carried out to discover new fields of application.

  17. Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.

    Directory of Open Access Journals (Sweden)

    Masami Watabe-Rudolph

    Full Text Available Atrophy of the olfactory epithelium (OE associated with impaired olfaction and dry nose represents one of the most common phenotypes of human aging. Impairment in regeneration of a functional olfactory epithelium can also occur in response to injury due to infection or nasal surgery. These complications occur more frequently in aged patients. Although age is the most unifying risk factor for atrophic changes and functional decline of the olfactory epithelium, little is known about molecular mechanisms that could influence maintenance and repair of the olfactory epithelium. Here, we analyzed the influence of telomere shortening (a basic mechanism of cellular aging on homeostasis and regenerative reserve in response to chemical induced injury of the OE in late generation telomere knockout mice (G3 mTerc(-/- with short telomeres compared to wild type mice (mTerc(+/+ with long telomeres. The study revealed no significant influence of telomere shortening on homeostatic maintenance of the OE during mouse aging. In contrast, the regenerative response to chemical induced injury of the OE was significantly impaired in G3 mTerc(-/- mice compared to mTerc(+/+ mice. Seven days after chemical induced damage, G3 mTerc(-/- mice exhibited significantly enlarged areas of persisting atrophy compared to mTerc(+/+ mice (p = 0.031. Telomere dysfunction was associated with impairments in cell proliferation in the regenerating epithelium. Deletion of the cell cycle inhibitor, Cdkn1a (p21 rescued defects in OE regeneration in telomere dysfunctional mice. Together, these data indicate that telomere shortening impairs the regenerative capacity of the OE by impairing cell cycle progression in a p21-dependent manner. These findings could be relevant for the impairment in OE function in elderly people.

  18. NORMAL GENE EXPRESSION IN MALE F344 RAT NASAL TRANSITIONAL/RESPIRATORY EPITHELIUM

    Science.gov (United States)

    Abstract The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity in rodents. Gene expression profiles were determined in order to provide normal baseline data for nasal transitional/respiratory epithelium from healthy rats. Ce...

  19. Gastrointestinal Stromal Tumors: A Case Report

    Directory of Open Access Journals (Sweden)

    Palankezhe Sashidharan

    2014-03-01

    Full Text Available Advances in the identification of gastrointestinal stromal tumors, its molecular and immunohiostochemical basis, and its management have been a watershed in the treatment of gastrointestinal tumors. This paradigm shift occurred over the last two decades and gastrointestinal stromal tumors have now come to be understood as rare gastrointestinal tract tumors with predictable behavior and outcome, replacing the older terminologies like leiomyoma, schwannoma or leiomyosarcoma. This report presents a case of gastric gastrointestinal stromal tumor operated recently in a 47-year-old female patient and the outcome, as well as literature review of the pathological identification, sites of origin, and factors predicting its behavior, prognosis and treatment.

  20. File list: InP.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: InP.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  3. File list: Pol.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  4. File list: InP.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  6. File list: NoD.Oth.10.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  7. File list: Pol.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  8. File list: ALL.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: DNS.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. Dynamics of Bovine Sperm Interaction with Epithelium Differ Between Oviductal Isthmus and Ampulla1

    Science.gov (United States)

    Ardon, Florencia; Markello, Ross D.; Hu, Lian; Deutsch, Zarah I.; Tung, Chih-Kuan; Wu, Mingming; Suarez, Susan S.

    2016-01-01

    In mammals, many sperm that reach the oviduct are held in a reservoir by binding to epithelium. To leave the reservoir, sperm detach from the epithelium; however, they may bind and detach again as they ascend into the ampulla toward oocytes. In order to elucidate the nature of binding interactions along the oviduct, we compared the effects of bursts of strong fluid flow (as would be caused by oviductal contractions), heparin, and hyperactivation on detachment of bovine sperm bound in vitro to epithelium on intact folds of isthmic and ampullar mucosa. Intact folds of oviductal mucosa were used to represent the strong attachments of epithelial cells to each other and to underlying connective tissue that exist in vivo. Effects of heparin on binding were tested because heparin binds to the Binder of SPerm (BSP) proteins that attach sperm to oviductal epithelium. Sperm bound by their heads to beating cilia on both isthmic and ampullar epithelia and could not be detached by strong bursts of fluid flow. Addition of heparin immediately detached sperm from isthmic epithelium but not ampullar epithelium. Addition of 4-aminopyridine immediately stimulated hyperactivation of sperm but did not detach them from isthmic or ampullar epithelium unless added with heparin. These observations indicate that the nature of binding of sperm to ampullar epithelium differs from that of binding to isthmic epithelium; specifically, sperm bound to isthmic epithelium can be detached by heparin alone, while sperm bound to ampullar epithelium requires both heparin and hyperactivation to detach from the epithelium. PMID:27605344

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  16. File list: ALL.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  17. File list: His.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  18. File list: His.Oth.10.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  19. File list: Oth.Oth.10.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  7. Cell proliferation in rat nasal respiratory epithelium following three months exposure to formaldehyde gas

    International Nuclear Information System (INIS)

    Monticello, T.M.; Morgan, K.T.

    1990-01-01

    Formaldehyde (HCHO), a ubiquitous chemical and rat nasal carcinogen, enhances cell proliferation in rat, monkey, and xenotransplanted human respiratory epithelium following short-term exposure. The present studies were designed to evaluate cell proliferation in relation to tumor induction in rat nasal respiratory epithelium following subchronic HCHO exposure. Male F-344 rats were whole-body exposed to either 0, 0.7, 2, 6, 10, or 15 ppm HCHO, for wither 4 d (6hr/d), 6 wks (5d/wk) or 3 months. Animals were labeled with tritiated thymidine prior to euthanasia. Nasal sections were processed for autoradiography and cell proliferation data was expressed as unit length labeling indices (ULLI). HCHO-induced lesions and increases in cell proliferation occurred in specific regions of the nose, primarily the wall of the lateral meatus and nasal septum of the anterior nasal cavity. Following 4 d exposure, significant elevations in cell proliferation were observed only in the 6, 10 and 15 ppm groups (16-, 18-, and 20-fold increase over control, respectively). Increases in ULLI were also present in the 6, 10 and 15 ppm groups after 6 wks of exposure (12-, 35-, and 40-fold increase over control). However, after 3 months exposure, elevations in ULLI were present only in the 10 and 15 ppm groups (9- and 14-fold increase over controls). These results demonstrate that (1) low levels of HCHO (0.7 and 2 ppm) do not increase cell proliferation in rat nasal respiratory epithelium; (2) 6 ppm HCHO induces transient increases in cell proliferation; and (3) clearly carcinogenic concentrations of HCHO (10 and 15 ppm) cause sustained elevations in cell proliferation which may play an important role in HCHO-induced carcinogenesis

  8. Activation of muscarinic acetylcholine receptors elicits pigment granule dispersion in retinal pigment epithelium isolated from bluegill.

    Science.gov (United States)

    González, Alfredo; Crittenden, Elizabeth L; García, Dana M

    2004-07-13

    In fish, melanin pigment granules in the retinal pigment epithelium disperse into apical projections as part of the suite of responses the eye makes to bright light conditions. This pigment granule dispersion serves to reduce photobleaching and occurs in response to neurochemicals secreted by the retina. Previous work has shown that acetylcholine may be involved in inducing light-adaptive pigment dispersion. Acetylcholine receptors are of two main types, nicotinic and muscarinic. Muscarinic receptors are in the G-protein coupled receptor superfamily, and five different muscarinic receptors have been molecularly cloned in human. These receptors are coupled to adenylyl cyclase, calcium mobilization and ion channel activation. To determine the receptor pathway involved in eliciting pigment granule migration, we isolated retinal pigment epithelium from bluegill and subjected it to a battery of cholinergic agents. The general cholinergic agonist carbachol induces pigment granule dispersion in isolated retinal pigment epithelium. Carbachol-induced pigment granule dispersion is blocked by the muscarinic antagonist atropine, by the M1 antagonist pirenzepine, and by the M3 antagonist 4-DAMP. Pigment granule dispersion was also induced by the M1 agonist 4-[N-(4-chlorophenyl) carbamoyloxy]-4-pent-2-ammonium iodide. In contrast the M2 antagonist AF-DX 116 and the M4 antagonist tropicamide failed to block carbachol-induced dispersion, and the M2 agonist arecaidine but-2-ynyl ester tosylate failed to elicit dispersion. Our results suggest that carbachol-mediated pigment granule dispersion occurs through the activation of Modd muscarinic receptors, which in other systems couple to phosphoinositide hydrolysis and elevation of intracellular calcium. This conclusion must be corroborated by molecular studies, but suggests Ca2+-dependent pathways may be involved in light-adaptive pigment dispersion.

  9. Activation of muscarinic acetylcholine receptors elicits pigment granule dispersion in retinal pigment epithelium isolated from bluegill

    Directory of Open Access Journals (Sweden)

    Crittenden Elizabeth L

    2004-07-01

    Full Text Available Abstract Background In fish, melanin pigment granules in the retinal pigment epithelium disperse into apical projections as part of the suite of responses the eye makes to bright light conditions. This pigment granule dispersion serves to reduce photobleaching and occurs in response to neurochemicals secreted by the retina. Previous work has shown that acetylcholine may be involved in inducing light-adaptive pigment dispersion. Acetylcholine receptors are of two main types, nicotinic and muscarinic. Muscarinic receptors are in the G-protein coupled receptor superfamily, and five different muscarinic receptors have been molecularly cloned in human. These receptors are coupled to adenylyl cyclase, calcium mobilization and ion channel activation. To determine the receptor pathway involved in eliciting pigment granule migration, we isolated retinal pigment epithelium from bluegill and subjected it to a battery of cholinergic agents. Results The general cholinergic agonist carbachol induces pigment granule dispersion in isolated retinal pigment epithelium. Carbachol-induced pigment granule dispersion is blocked by the muscarinic antagonist atropine, by the M1 antagonist pirenzepine, and by the M3 antagonist 4-DAMP. Pigment granule dispersion was also induced by the M1 agonist 4-[N-(4-chlorophenyl carbamoyloxy]-4-pent-2-ammonium iodide. In contrast the M2 antagonist AF-DX 116 and the M4 antagonist tropicamide failed to block carbachol-induced dispersion, and the M2 agonist arecaidine but-2-ynyl ester tosylate failed to elicit dispersion. Conclusions Our results suggest that carbachol-mediated pigment granule dispersion occurs through the activation of Modd muscarinic receptors, which in other systems couple to phosphoinositide hydrolysis and elevation of intracellular calcium. This conclusion must be corroborated by molecular studies, but suggests Ca2+-dependent pathways may be involved in light-adaptive pigment dispersion.

  10. Radiopharmaceuticals and the gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Frier, M. [Radiopharmacy Unit, Dept. of Medical Physics, Queens Medical Centre, Univ. Hospital Nottingham (United Kingdom); Perkins, A.C. [Radiopharmacy Unit, Dept. of Medical Physics, Queens Medical Centre, Univ. Hospital Nottingham (United Kingdom)

    1994-11-01

    A review is presented of the design of radiolabelled test meals for the evaluation of gastrointestinal function, including oesophageal transit, gastro-oesophageal reflux, gastric emptying, enterogastric reflux and transit through the whole bowel. Descriptions of different systems are presented, together with validations of the procedures used. Published methods for assessment of oesophageal transit show a marked degree of consistency, whereas gastric emptying studies employ a wide range of both liquid and solid test meals. Recommendations are made concerning the optimal system for investigation of each part of the gastrointestinal tract, but whichever system is adopted, it is important to employ some validation procedures, and to establish normal ranges in the population under study. (orig.)

  11. Gastrointestinal hormones and their targets

    DEFF Research Database (Denmark)

    Rehfeld, Jens F.

    2014-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone producing organ in the body. Modern biology makes...... it feasible to conceive the hormones under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization......, or differentiated maturation of the prohormone. By a combination of these mechanisms, more than 100 different hormonally active peptides are released from the gut. Gut hormone genes are also widely expressed in cells outside the gut, some only in extraintestinal endocrine cells and neurons but others also in other...

  12. An L-Fucose Operon in the Probiotic Lactobacillus rhamnosus GG Is Involved in Adaptation to Gastrointestinal Conditions.

    Science.gov (United States)

    Becerra, Jimmy E; Yebra, María J; Monedero, Vicente

    2015-06-01

    L-Fucose is a sugar present in human secretions as part of human milk oligosaccharides, mucins, and other glycoconjugates in the intestinal epithelium. The genome of the probiotic Lactobacillus rhamnosus GG (LGG) carries a gene cluster encoding a putative L-fucose permease (fucP), L-fucose catabolic pathway (fucI, fucK, fucU, and fucA), and a transcriptional regulator (fucR). The metabolism of L-fucose in LGG results in 1,2-propanediol production, and their fucI and fucP mutants displayed a severe and mild growth defect on L-fucose, respectively. Transcriptional analysis revealed that the fuc genes are induced by L-fucose and subject to a strong carbon catabolite repression effect. This induction was triggered by FucR, which acted as a transcriptional activator necessary for growth on L-fucose. LGG utilized fucosyl-α1,3-N-acetylglucosamine and contrarily to other lactobacilli, the presence of fuc genes allowed this strain to use the L-fucose moiety. In fucI and fucR mutants, but not in fucP mutant, L-fucose was not metabolized and it was excreted to the medium during growth on fucosyl-α1,3-N-acetylglucosamine. The fuc genes were induced by this fucosyl-disaccharide in the wild type and the fucP mutant but not in a fucI mutant, showing that FucP does not participate in the regulation of fuc genes and that L-fucose metabolism is needed for FucR activation. The l-fucose operon characterized here constitutes a new example of the many factors found in LGG that allow this strain to adapt to the gastrointestinal conditions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Precision Medicine in Gastrointestinal Pathology.

    Science.gov (United States)

    Wang, David H; Park, Jason Y

    2016-05-01

    -Precision medicine is the promise of individualized therapy and management of patients based on their personal biology. There are now multiple global initiatives to perform whole-genome sequencing on millions of individuals. In the United States, an early program was the Million Veteran Program, and a more recent proposal in 2015 by the president of the United States is the Precision Medicine Initiative. To implement precision medicine in routine oncology care, genetic variants present in tumors need to be matched with effective clinical therapeutics. When we focus on the current state of precision medicine for gastrointestinal malignancies, it becomes apparent that there is a mixed history of success and failure. -To present the current state of precision medicine using gastrointestinal oncology as a model. We will present currently available targeted therapeutics, promising new findings in clinical genomic oncology, remaining quality issues in genomic testing, and emerging oncology clinical trial designs. -Review of the literature including clinical genomic studies on gastrointestinal malignancies, clinical oncology trials on therapeutics targeted to molecular alterations, and emerging clinical oncology study designs. -Translating our ability to sequence thousands of genes into meaningful improvements in patient survival will be the challenge for the next decade.

  14. Hydrodynamics of stratified epithelium: Steady state and linearized dynamics

    Science.gov (United States)

    Yeh, Wei-Ting; Chen, Hsuan-Yi

    2016-05-01

    A theoretical model for stratified epithelium is presented. The viscoelastic properties of the tissue are assumed to be dependent on the spatial distribution of proliferative and differentiated cells. Based on this assumption, a hydrodynamic description of tissue dynamics at the long-wavelength, long-time limit is developed, and the analysis reveals important insights into the dynamics of an epithelium close to its steady state. When the proliferative cells occupy a thin region close to the basal membrane, the relaxation rate towards the steady state is enhanced by cell division and cell apoptosis. On the other hand, when the region where proliferative cells reside becomes sufficiently thick, a flow induced by cell apoptosis close to the apical surface enhances small perturbations. This destabilizing mechanism is general for continuous self-renewal multilayered tissues; it could be related to the origin of certain tissue morphology, tumor growth, and the development pattern.

  15. Nested Expression Domains for Odorant Receptors in Zebrafish Olfactory Epithelium

    Science.gov (United States)

    Weth, Franco; Nadler, Walter; Korsching, Sigrun

    1996-11-01

    The mapping of high-dimensional olfactory stimuli onto the two-dimensional surface of the nasal sensory epithelium constitutes the first step in the neuronal encoding of olfactory input. We have used zebrafish as a model system to analyze the spatial distribution of odorant receptor molecules in the olfactory epithelium by quantitative in situ hybridization. To this end, we have cloned 10 very divergent zebrafish odorant receptor molecules by PCR. Individual genes are expressed in sparse olfactory receptor neurons. Analysis of the position of labeled cells in a simplified coordinate system revealed three concentric, albeit overlapping, expression domains for the four odorant receptors analyzed in detail. Such regionalized expression should result in a corresponding segregation of functional response properties. This might represent the first step of spatial encoding of olfactory input or be essential for the development of the olfactory system.

  16. [Comparison of paired box genes 8 and 2 expression in epithelium tissues and the related tumors].

    Science.gov (United States)

    Song, Y; Huang, X; Shen, G H; Liu, X Y; Zhang, X

    2017-06-23

    Objective: To explore the expressional differences between paired box genes 2(Pax2) and 8 (Pax8) protein in different kinds of epitheliums and tumors, and to investigate the clinicopathologic significance. Methods: Expression levels of Pax2 and Pax8 protein were detected in 75 cases of different human epithelium tissues and 255 cases of different tumors on tissue microarray by immunohistochemistry. Results: Pax2 and Pax8 selectively expressed in different tissues. The positive rates of Pax8 protein expressed in the normal epithelium of the thyroid, urinary system and female reproductive system were 100% (2/2), 60.0% (3/5) and 76.9% (10/13), respectively. The positive rates of Pax2 expressed in the epithelium tissues of urinary system and the female reproductive system were 40.0% (2/5) and 38.5% (5/13) respectively. However, the expression of Pax2 protein was not detected in the normal thyroid epithelium. The positive rate of Pax8 protein expressing in the epithelium of reproductive system was significantly higher than that of Pax2 protein ( P <0.05). The tumors derived from different tissues also expressed different levels of protein Pax2 and Pax8. The positive rates of Pax8 in renal cell carcinoma, thyroid carcinoma and endometrial adenocarcinoma were 65.2% (15/23), 66.7% (10/15) and 80.0% (4/5), respectively. The positive rates of Pax2 in renal cell carcinoma, thyroid carcinoma and endometrial adenocarcinoma were 34.8% (8/23), 13.3% (2/15) and 20.0% (1/5), respectively. The positive rates of Pax8 protein expressed in renal cell carcinoma, thyroid carcinoma and endometrial adenocarcinoma were significantly higher than those of Pax2 protein ( P <0.05). The positive rates of Pax8 in ovarian serous carcinoma, endometrial carcinoma and clear cell carcinoma were 92.9% (26/28), 81.8% (9/11) and 82.4% (14/17), respectively. The positive rates of Pax2 in ovarian serous carcinoma, endometrial carcinoma and clear cell carcinoma were 28.6% (8/28), 9.1% (1/11) and 17.6% (3

  17. Characterization of the global profile of genes expressed in cervical epithelium by Serial Analysis of Gene Expression (SAGE

    Directory of Open Access Journals (Sweden)

    Piña-Sanchez Patricia

    2005-09-01

    Full Text Available Abstract Background Serial Analysis of Gene Expression (SAGE is a new technique that allows a detailed and profound quantitative and qualitative knowledge of gene expression profile, without previous knowledge of sequence of analyzed genes. We carried out a modification of SAGE methodology (microSAGE, useful for the analysis of limited quantities of tissue samples, on normal human cervical tissue obtained from a donor without histopathological lesions. Cervical epithelium is constituted mainly by cervical keratinocytes which are the targets of human papilloma virus (HPV, where persistent HPV infection of cervical epithelium is associated with an increase risk for developing cervical carcinomas (CC. Results We report here a transcriptome analysis of cervical tissue by SAGE, derived from 30,418 sequenced tags that provide a wealth of information about the gene products involved in normal cervical epithelium physiology, as well as genes not previously found in uterine cervix tissue involved in the process of epidermal differentiation. Conclusion This first comprehensive and profound analysis of uterine cervix transcriptome, should be useful for the identification of genes involved in normal cervix uterine function, and candidate genes associated with cervical carcinoma.

  18. Cytogenetic damage and postradiation restoration of eye cornea epithelium of Rodentia characterizing by different radiosensitivity

    International Nuclear Information System (INIS)

    Popova, M.F.; Bulyakova, N.V.

    1983-01-01

    Intensity of beam damage and reparation of eye cornea epithelium of animals inhabiting under different conditions and differing by radiosensitivity has been studied. Mice differing by high radiosensitivity have the hardest cytogenetic damage. Cornea epithelium of bank voles is more radiostable than that of mice. The most negligible damages of cornea epithelium is observed in Mongolian sandwort despite the fact that their total radiation stability is lower than that of bank voles. High protective-restoring properties of eye cornea epithelium of Mongolian sandwort are explained by the structure of epithelium cells diffe-- ring by a large number of cytoplasm

  19. Integrin Beta 1 Suppresses Multilayering of a Simple Epithelium

    Science.gov (United States)

    Chen, Jichao; Krasnow, Mark A.

    2012-01-01

    Epithelia are classified as either simple, a single cell layer thick, or stratified (multilayered). Stratified epithelia arise from simple epithelia during development, and transcription factor p63 functions as a key positive regulator of epidermal stratification. Here we show that deletion of integrin beta 1 (Itgb1) in the developing mouse airway epithelium abrogates airway branching and converts this monolayer epithelium into a multilayer epithelium with more than 10 extra layers. Mutant lung epithelial cells change mitotic spindle orientation to seed outer layers, and cells in different layers become molecularly and functionally distinct, hallmarks of normal stratification. However, mutant lung epithelial cells do not activate p63 and do not switch to the stratified keratin profile of epidermal cells. These data, together with previous data implicating Itgb1 in regulation of epidermal stratification, suggest that the simple-versus-stratified developmental decision may involve not only stratification inducers like p63 but suppressors like Itgb1 that prevent simple epithelia from inappropriately activating key steps in the stratification program. PMID:23285215

  20. Regeneration of tracheal epithelium using mouse induced pluripotent stem cells.

    Science.gov (United States)

    Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Otsuki, Koshi; Miyake, Masao; Hazama, Akihiro; Wada, Ikuo; Omori, Koichi

    2016-01-01

    Conclusion The findings demonstrated the potential use of induced pluripotent stem cells for regeneration of tracheal epithelium. Objective Autologous tissue implantation techniques using skin or cartilage are often applied in cases of tracheal defects with laryngeal inflammatory lesions and malignant tumor invasion. However, these techniques are invasive with an unstable clinical outcome. The purpose of this study was to investigate regeneration in a tracheal defect site of nude rats after implantation of ciliated epithelium that was differentiated from induced pluripotent stem cells. Method Embryoid bodies were formed from mouse induced pluripotent stem cells. They were cultured with growth factors for 5 days, and then cultured at the air-liquid interface. The degree of differentiation achieved prior to implantation was determined by histological findings and the results of real-time polymerase chain reaction. Embryoid bodies including ciliated epithelium were embedded into collagen gel that served as an artificial scaffold, and then implanted into nude rats, creating an 'air-liquid interface model'. Histological evaluation was performed 7 days after implantation. Results The ciliated epithelial structure survived on the lumen side of regenerated tissue. It was demonstrated histologically that the structure was composed of ciliated epithelial cells.

  1. Recovery of Vocal Fold Epithelium after Acute Phonotrauma.

    Science.gov (United States)

    Rousseau, Bernard; Kojima, Tsuyoshi; Novaleski, Carolyn K; Kimball, Emily E; Valenzuela, Carla V; Mizuta, Masanobu; Daniero, James J; Garrett, C Gaelyn; Sivasankar, M Preeti

    2017-01-01

    We investigated the timeline of tissue repair of vocal fold epithelium after acute vibration exposure using an in vivo rabbit model. Sixty-five New Zealand white breeder rabbits were randomized to 120 min of modal- or raised-intensity phonation. After the larynges were harvested at 0, 4, 8, and 24 h, and at 3 and 7 days, the vocal fold tissue was evaluated using electron microscopy and quantitative real-time polymerase chain reaction. There was an immediate decrease in the microprojection depth and height following raised-intensity phonation, paired with upregulation of cyclooxygenase-2. This initial 24-h period was also characterized by the significant downregulation of junction proteins. Interleukin 1β and transforming growth factor β1 were upregulated for 3 and 7 days, respectively, followed by an increase in epithelial cell surface depth at 3 and 7 days. These data appear to demonstrate a shift from inflammatory response to the initiation of a restorative process in the vocal fold epithelium between 24 h and 3 days. Despite the initial damage from raised-intensity phonation, the vocal fold epithelium demonstrates a remarkable capacity for the expeditious recovery of structural changes from transient episodes of acute phonotrauma. While structurally intact, the return of functional barrier integrity may be delayed by repeated episodes of phonotrauma and may also play an important role in the pathophysiology of vocal fold lesions. © 2017 S. Karger AG, Basel.

  2. Solitary chemoreceptor cell proliferation in adult nasal epithelium.

    Science.gov (United States)

    Gulbransen, Brian D; Finger, Thomas E

    2005-03-01

    Nasal trigeminal chemosensitivity in mice and rats is mediated in part by solitary chemoreceptor cells (SCCs) in the nasal epithelium (Finger et al., 2003). Many nasal SCCs express the G-protein alpha-gustducin as well as other elements of the bitter-taste signaling cascade including phospholipase Cbeta2, TRPM5 and T2R bitter-taste receptors. While some populations of sensory cells are replaced throughout life (taste and olfaction), others are not (hair cells and carotid body chemoreceptors). These experiments were designed to test whether new SCCs are generated within the epithelium of adult mice. Wild type C57/B6 mice were injected with the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to label dividing cells. At various times after injection (1-40 days), the mice were perfused with 4% paraformaldehyde and prepared for dual-label immunocytochemistry. Double labeled cells were detected as early as 3 days post BrdU injection and remained for as long as 12 days post-injection suggesting that SCCs do undergo turnover like the surrounding nasal epithelium. No BrdU labeled cells were detected after 24 days suggesting relatively rapid replacement of the SCCs.

  3. Biological and genetic properties of the p53 null preneoplastic mammary epithelium

    Science.gov (United States)

    Medina, Daniel; Kittrell, Frances S.; Shepard, Anne; Stephens, L. Clifton; Jiang, Cheng; Lu, Junxuan; Allred, D. Craig; McCarthy, Maureen; Ullrich, Robert L.

    2002-01-01

    The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.

  4. Spatial and spectral analysis of corneal epithelium injury using hyperspectral images

    Science.gov (United States)

    Md Noor, Siti Salwa; Michael, Kaleena; Marshall, Stephen; Ren, Jinchang

    2017-12-01

    Eye assessment is essential in preventing blindness. Currently, the existing methods to assess corneal epithelium injury are complex and require expert knowledge. Hence, we have introduced a non-invasive technique using hyperspectral imaging (HSI) and an image analysis algorithm of corneal epithelium injury. Three groups of images were compared and analyzed, namely healthy eyes, injured eyes, and injured eyes with stain. Dimensionality reduction using principal component analysis (PCA) was applied to reduce massive data and redundancies. The first 10 principal components (PCs) were selected for further processing. The mean vector of 10 PCs with 45 pairs of all combinations was computed and sent to two classifiers. A quadratic Bayes normal classifier (QDC) and a support vector classifier (SVC) were used in this study to discriminate the eleven eyes into three groups. As a result, the combined classifier of QDC and SVC showed optimal performance with 2D PCA features (2DPCA-QDSVC) and was utilized to classify normal and abnormal tissues, using color image segmentation. The result was compared with human segmentation. The outcome showed that the proposed algorithm produced extremely promising results to assist the clinician in quantifying a cornea injury.

  5. The effects of hyaluronic acid vaginal gel on the vaginal epithelium of ovariectomized rats.

    Science.gov (United States)

    Liu, Shuai-Bin; Liu, Shao-Li; Gan, Xiao-Ling; Zhou, Qin; Hu, Li-Na

    2015-03-01

    Hyaluronic acid is one of the best materials of water retention which can be used in vaginal atrophy. This study is to evaluate the role and mechanism of the hyaluronic acid vaginal gel (Hyalofemme) in the vaginal epithelium of ovariectomized rats. Sixty SD rats were randomly divided into control group (Sham ovariectomy, Sham-OVX), tendency group (ovariectomy, OVX), and experiment group (ovariectomy+Hyalofemme, OVX+Hyalofemme). The hyaluronic acid vaginal gel was administered local vaginal therapy to the experiment group with cytologicaly confirmed vaginal atrophy. The doses were adjusted by animal weight according to human dosage. After daily treatment for 14 days, VEGF and P-AKT activations were detected by Western blot in the experiment group. The hyaluronic acid vaginal gel proved to be very effective in the cytological reversal of vaginal atrophy but did not increase uterine weight. Vaginal microecosystem indicators were negative in the control group and the experiment group. By contrast, the indicators were positive in the tendency group. Hyaluronic acid vaginal gel is effective in the reversal of vaginal atrophy and is beneficial for improving vaginal microecosystem in the postmenopausal rat model. The hyaluronic acid vaginal gel can also improve the repair capacity of the vaginal epithelium.

  6. Segment-specific responses of intestinal epithelium transcriptome to in-feed antibiotics in pigs.

    Science.gov (United States)

    Yu, Kaifan; Mu, Chunlong; Yang, Yuxiang; Su, Yong; Zhu, Weiyun

    2017-10-01

    Despite widespread use of antibiotics for treatment of human diseases and promotion of growth of agricultural animals, our understanding of their effects on the host is still very limited. We used a model in which pigs were fed with or without a cocktail of antibiotics and found, based on the denaturing gradient gel electrophoresis (DGGE) patterns, that the fecal bacteria from the treatment and control animals were distinct. Furthermore, the total bacterial population in the feces tended to be decreased by the antibiotic treatment ( P = 0.07), and the counts of Lactobacillus and Clostridium XIVa were significantly reduced ( P epithelium, we assessed gene expression profiles of the jejunum and ileum and their response to antibiotic administration. The results indicate that in-feed antibiotics increased expression of genes involved in immune functions in both the jejunum and ileum, some of which were clustered in the coexpression network. Gene ontology terms of metabolic processes were altered predominantly in the jejunum but not in the ileum. Notably, antibiotics diminished intestinal segment-specific transcriptional changes, especially for genes associated with metabolic functions. This study reveals segment-specific responses of host intestinal epithelium to in-feed antibiotics, which can be a valuable resource for deciphering antibiotic-microbiota-host interactions. Copyright © 2017 the American Physiological Society.

  7. Artificial Cochlear Sensory Epithelium with Functions of Outer Hair Cells Mimicked Using Feedback Electrical Stimuli

    Directory of Open Access Journals (Sweden)

    Tetsuro Tsuji

    2018-05-01

    Full Text Available We report a novel vibration control technique of an artificial auditory cochlear epithelium that mimics the function of outer hair cells in the organ of Corti. The proposed piezoelectric and trapezoidal membrane not only has the acoustic/electric conversion and frequency selectivity of the previous device developed mainly by one of the authors and colleagues, but also has a function to control local vibration according to sound stimuli. Vibration control is achieved by applying local electrical stimuli to patterned electrodes on an epithelium made using micro-electro-mechanical system technology. By choosing appropriate phase differences between sound and electrical stimuli, it is shown that it is possible to both amplify and dampen membrane vibration, realizing better control of the response of the artificial cochlea. To be more specific, amplification and damping are achieved when the phase difference between the membrane vibration by sound stimuli and electrical stimuli is zero and π , respectively. We also demonstrate that the developed control system responds automatically to a change in sound frequency. The proposed technique can be applied to mimic the nonlinear response of the outer hair cells in a cochlea, and to realize a high-quality human auditory system.

  8. Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis.

    Science.gov (United States)

    Bianchi, Enrica; Scarinci, Fabio; Ripandelli, Guido; Feher, Janos; Pacella, Elena; Magliulo, Giuseppe; Gabrieli, Corrado Balacco; Plateroti, Rocco; Plateroti, Pasquale; Mignini, Fiorenzo; Artico, Marco

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye.

  9. Toll-8/Tollo negatively regulates antimicrobial response in the Drosophila respiratory epithelium.

    Directory of Open Access Journals (Sweden)

    Idir Akhouayri

    2011-10-01

    Full Text Available Barrier epithelia that are persistently exposed to microbes have evolved potent immune tools to eliminate such pathogens. If mechanisms that control Drosophila systemic responses are well-characterized, the epithelial immune responses remain poorly understood. Here, we performed a genetic dissection of the cascades activated during the immune response of the Drosophila airway epithelium i.e. trachea. We present evidence that bacteria induced-antimicrobial peptide (AMP production in the trachea is controlled by two signalling cascades. AMP gene transcription is activated by the inducible IMD pathway that acts non-cell autonomously in trachea. This IMD-dependent AMP activation is antagonized by a constitutively active signalling module involving the receptor Toll-8/Tollo, the ligand Spätzle2/DNT1 and Ect-4, the Drosophila ortholog of the human Sterile alpha and HEAT/ARMadillo motif (SARM. Our data show that, in addition to Toll-1 whose function is essential during the systemic immune response, Drosophila relies on another Toll family member to control the immune response in the respiratory epithelium.

  10. Integrins beta 5, beta 3 and alpha v are apically distributed in endometrial epithelium.

    Science.gov (United States)

    Aplin, J D; Spanswick, C; Behzad, F; Kimber, S J; Vićovac, L

    1996-07-01

    Several adhesion molecules have been shown to occur at the surface of endometrial cells. One of these is the integrin alpha v subunit which associates with various beta chains including beta 5. We demonstrate the presence of integrin beta 5 polypeptide in human endometrial epithelial cells throughout the menstrual cycle using immunocytochemistry with monospecific antibodies, and at the mRNA level by thermal amplification from endometrial cDNA. Integrin beta 5 is also found in a population of bone marrow-derived cells. A notable feature of the distribution of the beta 5 subunit in the glandular and luminal epithelium is its apical localization, which may suggest an involvement in implantation. However, no evidence was found for regulated expression of epithelial beta 5. In mouse, the beta 5 subunit is found at both the apical and basal surface of epithelial cells and expression is essentially oestrous cycle-independent. Comparisons are made in both species with the distribution of the alpha v and beta 3 subunits which also localize to the apical epithelium.

  11. Laboratory Diagnosis of Parasites from the Gastrointestinal Tract.

    Science.gov (United States)

    Garcia, Lynne S; Arrowood, Michael; Kokoskin, Evelyne; Paltridge, Graeme P; Pillai, Dylan R; Procop, Gary W; Ryan, Norbert; Shimizu, Robyn Y; Visvesvara, Govinda

    2018-01-01

    This Practical Guidance for Clinical Microbiology document on the laboratory diagnosis of parasites from the gastrointestinal tract provides practical information for the recovery and identification of relevant human parasites. The document is based on a comprehensive literature review and expert consensus on relevant diagnostic methods. However, it does not include didactic information on human parasite life cycles, organism morphology, clinical disease, pathogenesis, treatment, or epidemiology and prevention. As greater emphasis is placed on neglected tropical diseases, it becomes highly probable that patients with gastrointestinal parasitic infections will become more widely recognized in areas where parasites are endemic and not endemic. Generally, these methods are nonautomated and require extensive bench experience for accurate performance and interpretation. Copyright © 2017 American Society for Microbiology.

  12. Behavioural medicine and gastrointestinal disorders: the promise of positive psychology.

    Science.gov (United States)

    Keefer, Laurie

    2018-04-12

    Psychosocial risk factors linked to brain-gut dysregulation are prevalent across the spectrum of gastrointestinal disorders and are associated with poor patient outcomes. Robust and reproducible data in the areas of behavioural intervention science and the brain-gut axis have led to major advances in patient care, including the routine use of brain-gut psychotherapies to manage digestive symptoms and optimize coping. The logical next step for the emerging field of psychogastroenterology is to develop a scientific framework that enables the identification of those individual characteristics and coping styles that buffer patients against the negative psychological effects of chronic gastrointestinal disorders. A shift towards a strength-based, positive psychological science of gastrointestinal disorders could facilitate the integration of early, effective psychological care into gastroenterology practice. In this Perspective, I discuss the potential role of three human strengths with relevance to gastrointestinal health - resilience, optimism and self-regulation - and how these three constructs can be cultivated through existing or emerging brain-gut psychotherapies.

  13. Probiotics for Gastrointestinal Conditions: A Summary of the Evidence.

    Science.gov (United States)

    Wilkins, Thad; Sequoia, Jacqueline

    2017-08-01

    Probiotics contain microorganisms, most of which are bacteria similar to the beneficial bacteria that occur naturally in the human gut. Probiotics have been widely studied in a variety of gastrointestinal diseases. The most-studied species include Lactobacillus, Bifidobacterium, and Saccharomyces. However, a lack of clear guidelines on when to use probiotics and the most effective probiotic for different gastrointestinal conditions may be confusing for family physicians and their patients. Probiotics have an important role in the maintenance of immunologic equilibrium in the gastrointestinal tract through the direct interaction with immune cells. Probiotic effectiveness can be species-, dose-, and disease-specific, and the duration of therapy depends on the clinical indication. There is high-quality evidence that probiotics are effective for acute infectious diarrhea, antibiotic-associated diarrhea, Clostridium difficile- associated diarrhea, hepatic encephalopathy, ulcerative colitis, irritable bowel syndrome, functional gastrointestinal disorders, and necrotizing enterocolitis. Conversely, there is evidence that probiotics are not effective for acute pancreatitis and Crohn disease. Probiotics are safe for infants, children, adults, and older patients, but caution is advised in immunologically vulnerable populations.

  14. Ecology and pathogenicity of gastrointestinal Streptococcus bovis.

    Science.gov (United States)

    Herrera, Paul; Kwon, Young Min; Ricke, Steven C

    2009-01-01

    Streptococcus bovis is an indigenous resident in the gastrointestinal tracts of both humans and animals. S. bovis is one of the major causes of bacterial endocarditis and has been implicated in the incidence of human colon cancer, possibly due to chronic inflammatory response at the site of intestinal colonization. Certain feeding regimens in ruminants can lead to overgrowth of S. bovis in the rumen, resulting in the over-production of lactate and capsular polysaccharide causing acute ruminal acidosis and bloat, respectively. There are multiple strategies in controlling acute lactic acidosis and bloat. The incidence of the two diseases may be controlled by strict dietary management. Gradual introduction of grain-based diets and the feeding of coarsely chopped roughage decrease the incidence of the two disease entities. Ionophores, which have been used to enhance feed conversion and growth rate in cattle, have been shown to inhibit the growth of lactic acid bacteria in the rumen. Other methods of controlling lactic acid bacteria in the ruminal environment (dietary supplementation of long-chain fatty acids, induction of passive and active immune responses to the bacteria, and the use of lytic bacteriophages) have also been investigated. It is anticipated that through continued in-depth ecological analysis of S. bovis the characteristics responsible for human and animal pathogenesis would be sufficiently identified to a point where more effective control strategies for the control of this bacteria can be developed.

  15. Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders

    Science.gov (United States)

    Kelesidis, Theodoros

    2012-01-01

    Several clinical trials and experimental studies strongly suggest a place for Saccharomyces boulardii as a biotherapeutic agent for the prevention and treatment of several gastrointestinal diseases. S. boulardii mediates responses resembling the protective effects of the normal healthy gut flora. The multiple mechanisms of action of S. boulardii and its properties may explain its efficacy and beneficial effects in acute and chronic gastrointestinal diseases that have been confirmed by clinical trials. Caution should be taken in patients with risk factors for adverse events. This review discusses the evidence for efficacy and safety of S. boulardii as a probiotic for the prevention and therapy of gastrointestinal disorders in humans. PMID:22423260

  16. A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration.

    Science.gov (United States)

    Feng, Lili; Ju, Meihua; Lee, Kei Ying V; Mackey, Ashley; Evangelista, Mariasilvia; Iwata, Daiju; Adamson, Peter; Lashkari, Kameran; Foxton, Richard; Shima, David; Ng, Yin Shan

    2017-10-01

    Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. PPARs Signaling and Cancer in the Gastrointestinal System

    Directory of Open Access Journals (Sweden)

    Valerio Pazienza

    2012-01-01

    Full Text Available Nowadays, the study of the peroxisome proliferators activated receptors (PPARs as potential targets for cancer prevention and therapy has gained a strong interest. From a biological point of view, the overall responsibility of PPARs in cancer development and progression is still controversial since several studies report both antiproliferative and tumor-promoting actions for these signaling molecules in human cancer cells and animal models. In this paper, we discuss PPARs functions in the context of different types of gastrointestinal cancer.

  18. Oral microbiome and oral and gastrointestinal cancer risk

    OpenAIRE

    Ahn, Jiyoung; Chen, Calvin Y.; Hayes, Richard B.

    2012-01-01

    A growing body of evidence implicates human oral bacteria in the etiology of oral and gastrointestinal cancers. Epidemiological studies consistently report increased risks of these cancers in men and women with periodontal disease or tooth loss, conditions caused by oral bacteria. More than 700 bacterial species inhabit the oral cavity, including at least 11 bacterial phyla and 70 genera. Oral bacteria may activate alcohol and smoking-related carcinogens locally or act systemically, through c...

  19. Upper gastrointestinal bleeding in patients with CKD.

    Science.gov (United States)

    Liang, Chih-Chia; Wang, Su-Ming; Kuo, Huey-Liang; Chang, Chiz-Tzung; Liu, Jiung-Hsiun; Lin, Hsin-Hung; Wang, I-Kuan; Yang, Ya-Fei; Lu, Yueh-Ju; Chou, Che-Yi; Huang, Chiu-Ching

    2014-08-07

    Patients with CKD receiving maintenance dialysis are at risk for upper gastrointestinal bleeding. However, the risk of upper gastrointestinal bleeding in patients with early CKD who are not receiving dialysis is unknown. The hypothesis was that their risk of upper gastrointestinal bleeding is negatively linked to renal function. To test this hypothesis, the association between eGFR and risk of upper gastrointestinal bleeding in patients with stages 3-5 CKD who were not receiving dialysis was analyzed. Patients with stages 3-5 CKD in the CKD program from 2003 to 2009 were enrolled and prospectively followed until December of 2012 to monitor the development of upper gastrointestinal bleeding. The risk of upper gastrointestinal bleeding was analyzed using competing-risks regression with time-varying covariates. In total, 2968 patients with stages 3-5 CKD who were not receiving dialysis were followed for a median of 1.9 years. The incidence of upper gastrointestinal bleeding per 100 patient-years was 3.7 (95% confidence interval, 3.5 to 3.9) in patients with stage 3 CKD, 5.0 (95% confidence interval, 4.8 to 5.3) in patients with stage 4 CKD, and 13.9 (95% confidence interval, 13.1 to 14.8) in patients with stage 5 CKD. Higher eGFR was associated with a lower risk of upper gastrointestinal bleeding (P=0.03), with a subdistribution hazard ratio of 0.93 (95% confidence interval, 0.87 to 0.99) for every 5 ml/min per 1.73 m(2) higher eGFR. A history of upper gastrointestinal bleeding (Pupper gastrointestinal bleeding risk. In patients with CKD who are not receiving dialysis, lower renal function is associated with higher risk for upper gastrointestinal bleeding. The risk is higher in patients with previous upper gastrointestinal bleeding history and low serum albumin. Copyright © 2014 by the American Society of Nephrology.

  20. Gastrointestinal helminths in migratory Camel

    Directory of Open Access Journals (Sweden)

    S G Rewatkar

    Full Text Available Survey of gastrointestinal helminth parasites in camel migrated from U.P., M.P., and Rajasthan at Nagpur region was carried out in early summer, 2008. Total 28 samples (12 males and 16 females were collected from different places of Nagpur region. They revealed parasites as Trichuris sp.(50%, Strongyloides sp.(32.14%, Trichostrongylus sp.(10.71%, Nematodirus sp.(10.71%, Haemonchus sp.(14.28%, Eurytrema sp.(21.42% ,Eimeria sp.(25%, Entamoeba sp.(17.85% and Balantidium sp.(7.14%.All were found positive for mixed helminthic infection. [Vet World 2009; 2(7.000: 258-258