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Sample records for efficient colonic mucosal

  1. Gut microbiota utilize immunoglobulin A for mucosal colonization.

    Science.gov (United States)

    Donaldson, G P; Ladinsky, M S; Yu, K B; Sanders, J G; Yoo, B B; Chou, W-C; Conner, M E; Earl, A M; Knight, R; Bjorkman, P J; Mazmanian, S K

    2018-05-18

    The immune system responds vigorously to microbial infection while permitting lifelong colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We found that a regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA) in mice. Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo. The IgA response was required for B. fragilis (and other commensal species) to occupy a defined mucosal niche that mediates stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  2. Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation.

    Science.gov (United States)

    Chaloner, A; Rao, A; Al-Chaer, E D; Greenwood-Van Meerveld, B

    2010-02-01

    Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liquid stool). Colonic tissue was isolated for histology and myeloperoxidase levels. The colonic mucosa was placed in modified Ussing chambers for measurements of permeability and short-circuit current responses to forskolin, electrical field stimulation, and carbachol. Segments of colonic musculature were placed in organ baths and contractile response to potassium chloride, electrical field stimulation, and carbachol were determined. In adult rats that experienced neonatal colonic irritation, no significant changes in colonic histology or myeloperoxidase activity were observed; however, stool consistency scores were increased. Mucosal permeability, measured as an increase in basal conductance, was significantly increased but no changes in short-circuit current responses were observed. In adulthood, rats that underwent colorectal distension as neonates exhibited an elevated smooth muscle contractile response to potassium chloride, but no changes in response to electrical field stimulation or carbachol. In summary, neonatal colonic irritation, shown previously to produce colonic hypersensitivity, leads to significant alterations in colonic mucosal and smooth muscle function characterized by loose stools, increased mucosal permeability, and increased smooth muscle contractility in the absence of colon inflammation in adulthood. Published by Elsevier Ltd.

  3. Colon mucosal cells after high-dose fractional irradiation

    International Nuclear Information System (INIS)

    Zorc-Pleskovic, R.; Vraspir-Porenta, O.; Petrovic, D.; Zorc, M.; Pleskovic, L.

    2000-01-01

    The aim of this study was to investigate histological and stereological changes in cryptal enterocytes, mucosal lymphocytes and mast cells 10 days after irradiation. For experimental model, 24 Beagle dogs 1-2 years old were used. Twelve dogs were irradiated 20 days with 32 Gy over the whole pelvis and tail. Another 12 dogs represented a control group. For the detection of apoptosis, the TUNEL technique was used. Histological and stereological analyses were performed using a Wild sampling microscope M 1000. In the irradiated group, volume density (P < 0.01), numerical density (P < 0.05) and average volume of lymphocytes (P < 0.001) were significantly lower than in the nonirradiated group. Numerical areal density of mast cells in the irradiated group was also significantly lower (P < 0.05). Volume density (P < 0.001) and average volume of mast cells (P < 0.001) were significantly higher in the irradiated group. The results of our experiments show that irradiation causes injury and loss of lymphocytes and mast cells in the colon mucosa. Apoptosis was detected in enterocytes and lymphocytes in the irradiated group and in nonirradiated group in equal numbers (2.5 ± 0.3 vs. 2.3 ± 0.3; ns.), suggesting that 10 days after high-dose irradiation, the cell loss is not due to apoptosis. (author)

  4. Standard colonic lavage alters the natural state of mucosal-associated microbiota in the human colon.

    Directory of Open Access Journals (Sweden)

    Laura Harrell

    Full Text Available Past studies of the human intestinal microbiota are potentially confounded by the common practice of using bowel-cleansing preparations. We examined if colonic lavage changes the natural state of enteric mucosal-adherent microbes in healthy human subjects.Twelve healthy individuals were divided into three groups; experimental group, control group one, and control group two. Subjects in the experimental group underwent an un-prepped flexible sigmoidoscopy with biopsies. Within two weeks, subjects were given a standard polyethylene glycol-based bowel cleansing preparation followed by a second flexible sigmoidoscopy. Subjects in control group one underwent two un-prepped flexible sigmoidoscopies within one week. Subjects in the second control group underwent an un-prepped flexible sigmoidoscopy followed by a second flexible sigmoidoscopy after a 24-hour clear liquid diet within one week. The mucosa-associated microbial communities from the two procedures in each subject were compared using 16S rRNA gene based terminal restriction fragment length polymorphism (T-RFLP, and library cloning and sequencing.Clone library sequencing analysis showed that there were changes in the composition of the mucosa-associated microbiota in subjects after colonic lavage. These changes were not observed in our control groups. Standard bowel preparation altered the diversity of mucosa-associated microbiota. Taxonomic classification did not reveal significant changes at the phylum level, but there were differences observed at the genus level.Standard bowel cleansing preparation altered the mucosal-adherent microbiota in all of our subjects, although the degree of change was variable. These findings underscore the importance of considering the confounding effects of bowel preparation when designing experiments exploring the gut microbiota.

  5. Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.

    Science.gov (United States)

    Baldauf, K J; Royal, J M; Kouokam, J C; Haribabu, B; Jala, V R; Yaddanapudi, K; Hamorsky, K T; Dryden, G W; Matoba, N

    2017-07-01

    Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium. The clinical relevance of CTBp-induced impacts on colonic mucosa was examined. In a human colon epithelial model using Caco2 cells, CTBp, but not the non-GM1-binding mutant G33D-CTBp, induced TGFβ-mediated wound healing. In a dextran sodium sulfate (DSS) acute colitis mouse model, oral administration of CTBp protected against colon mucosal damage as manifested by mitigated body weight loss, decreased histopathological scores, and blunted escalation of inflammatory cytokine levels while inducing wound healing-related genes. Furthermore, biweekly oral administration of CTBp significantly reduced disease severity and tumorigenesis in the azoxymethane/DSS model of ulcerative colitis and colon cancer. Altogether, these results demonstrate CTBp's ability to enhance mucosal healing in the colon, highlighting its potential application in ulcerative colitis therapy besides cholera vaccination.

  6. A characterization of anaerobic colonization and associated mucosal adaptations in the undiseased ileal pouch.

    LENUS (Irish Health Repository)

    Smith, F M

    2012-02-03

    INTRODUCTION: The resolution of pouchitis with metronidazole points to an anaerobic aetiology. Pouchitis is mainly seen in patients with ulcerative colitis pouches (UCP). We have recently found that sulphate reducing bacteria (SRB), a species of strict anaerobe, colonize UCP exclusively. Herein, we aimed to correlate levels of different bacterial species (including SRB) with mucosal inflammation and morphology. METHODS: Following ethical approval, fresh faecal samples and mucosal biopsies were taken from 9 patients with UCP and 5 patients with familial adenomatous polyposis pouches (FAPP). For the purposes of comparison, faecal samples and mucosal biopsies were also taken from the stomas of 7 of the 9 patients with UC (UCS). Colonization by four types of strict anaerobes (SRB, Clostridium perfringens, Bifidobacteria and Bacteroides) as well as by three types of facultative anaerobes (Enterococci, Coliforms and Lactobacilli) was evaluated. Inflammatory scores and mucosal morphology were assessed histologically in a blinded fashion by a pathologist. RESULTS: In general, strict anaerobes predominated over facultative in the UCP (P = 0.041). SRB were present in UCP exclusively. Even after exclusion of SRB from total bacterial counts, strict anaerobes still predominated. In the UCS, facultative anaerobes predominated. Strict and facultative anaerobes were present at similar levels in the FAPP. Enterococci were present at significantly reduced levels in the UCP when compared with the UCS (P = 0.031). When levels of SRB and other anaerobic species were individually correlated with mucosal inflammation and morphology, no trends were observed. CONCLUSION: We have previously identified that SRB exclusively colonize UCP. In addition we have now identified a novel increase in the strict\\/facultative anaerobic ratio within the UCP compared to UCS. These stark differences in bacterial colonization, however, appear to have limited impact on mucosal inflammation or morphology.

  7. Effectiveness of India ink as a long-term colonic mucosal marker.

    Science.gov (United States)

    Fennerty, M B; Sampliner, R E; Hixson, L J; Garewal, H S

    1992-01-01

    We prospectively studied the use of India ink as a long-term or "permanent" mucosal marker as part of a study investigating the natural history of diminutive distal colorectal polyps. Twenty-six patients had 32 India ink tatoos implanted. The tatoo sites of the 19 patients who were followed at least 6 months continued to display intensely stained mucosa at the original sites. No side effects or complications were encountered. India ink appears to be a safe and effective long-term marker for colonic mucosal lesions.

  8. Modulation of Mucosal Immune Response, Tolerance and Proliferation in Mice Colonized by the Mucin-Degrader Akkermansia muciniphila

    Directory of Open Access Journals (Sweden)

    Muriel eDerrien

    2011-08-01

    Full Text Available Epithelial cells of the mammalian intestine are covered with a mucus layer that prevents direct contact with intestinal microbes but also constitutes a substrate for mucus-degrading bacteria. To study the effect of mucus degradation on the host-response, germ-free mice were colonized with Akkermansia muciniphila. This anaerobic bacterium belonging to the Verrucomicrobia is specialized in the degradation of mucin, the glycoprotein present in mucus, and found in high numbers in the intestinal tract of human and other mammalian species. Efficient colonization of A. muciniphila was observed with highest numbers in the cecum, where most mucin is produced. In contrast, following colonization by Lactobacillus plantarum, a facultative anaerobe belonging to the Firmicutes that ferments carbohydrates, similar cell-numbers were found at all intestinal sites. Whereas A. muciniphila was located closely associated with the intestinal cells, L. plantarum was exclusively found in the lumen. The global transcriptional host response was determined in intestinal biopsies and revealed a consistent, site-specific and unique modulation of about 750 genes in mice colonized by A. muciniphila and over 1500 genes after colonization by L. plantarum. Pathway reconstructions showed that colonization by A. muciniphila altered mucosal gene expression profiles towards increased expression of genes involved in immune responses and cell fate determination, while colonization by L. plantarum led to up-regulation of lipid metabolism. These indicate that the colonizers induce host responses that are specific per intestinal location. In conclusion, we propose that A. muciniphila modulates pathways involved in establishing homeostasis for basal metabolism and immune tolerance towards commensal microbiota.

  9. Human colon tissue in organ culture: calcium and multi-mineral-induced mucosal differentiation.

    Science.gov (United States)

    Dame, Michael K; Veerapaneni, Indiradevi; Bhagavathula, Narasimharao; Naik, Madhav; Varani, James

    2011-01-01

    We have recently shown that a multi-mineral extract from the marine red algae, Lithothamnion calcareum, suppresses colon polyp formation and inflammation in mice. In the present study, we used intact human colon tissue in organ culture to compare responses initiated by Ca(2+) supplementation versus the multi-mineral extract. Normal human colon tissue was treated for 2 d in culture with various concentrations of calcium or the mineral-rich extract. The tissue was then prepared for histology/immunohistochemistry, and the culture supernatants were assayed for levels of type I procollagen and type I collagen. At higher Ca(2+) concentrations or with the mineral-rich extract, proliferation of epithelial cells at the base and walls of the mucosal crypts was suppressed, as visualized by reduced Ki67 staining. E-cadherin, a marker of differentiation, was more strongly expressed at the upper third of the crypt and at the luminal surface. Treatment with Ca(2+) or with the multi-mineral extract influenced collagen turnover, with decreased procollagen and increased type I collagen. These data suggest that calcium or mineral-rich extract has the capacity to (1) promote differentiation in human colon tissue in organ culture and (2) modulate stromal function as assessed by increased levels of type I collagen. Taken together, these data suggest that human colon tissue in organ culture (supporting in vivo finding in mice) will provide a valuable model for the preclinical assessment of agents that regulate growth and differentiation in the colonic mucosa.

  10. Interactions between bacteria and the intestinal mucosa: Do enteric neurotransmitters acting on epithelium cells influence mucosal colonization or infection?

    Science.gov (United States)

    The mechanisms governing the ability of bacteria to adhere to and colonize human and animal hosts in health and disease are still incompletely understood. Throughout the extensive mucosal surfaces of the body that are in contact with the external environment, epithelial cells represent the first po...

  11. Integrative Transcriptomic and Metabonomic Molecular Profiling of Colonic Mucosal Biopsies Indicates a Unique Molecular Phenotype for Ulcerative Colitis

    DEFF Research Database (Denmark)

    Rantalainen, Mattias; Bjerrum, Jacob Tveiten; Olsen, Jørgen

    2015-01-01

    characterized the molecular phenotype of ulcerative colitis through transcriptomic and metabonomic profiling of colonic mucosal biopsies from patients and controls. We have characterized the extent to which metabonomic and transcriptomic molecular phenotypes are associated with ulcerative colitis versus...... transcriptomic and metabonomic data have previously been shown to predict the clinical course of ulcerative colitis and related clinical phenotypes, indicating that molecular phenotypes reveal molecular changes associated with the disease. Our analyses indicate that variables of both transcriptomics...... and metabonomics are associated with disease case and control status, that a large proportion of transcripts are associated with at least one metabolite in mucosal colonic biopsies, and that multiple pathways are connected to disease-related metabolites and transcripts....

  12. Chronic ethanol feeding promotes azoxymethane and dextran sulfate sodium-induced colonic tumorigenesis potentially by enhancing mucosal inflammation

    International Nuclear Information System (INIS)

    Shukla, Pradeep K.; Chaudhry, Kamaljit K.; Mir, Hina; Gangwar, Ruchika; Yadav, Nikki; Manda, Bhargavi; Meena, Avtar S.; Rao, RadhaKrishna

    2016-01-01

    Alcohol consumption is one of the major risk factors for colorectal cancer. However, the mechanism involved in this effect of alcohol is unknown. We evaluated the effect of chronic ethanol feeding on azoxymethane and dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in mouse colon. Inflammation in colonic mucosa was assessed at a precancerous stage by evaluating mucosal infiltration of neutrophils and macrophages, and analysis of cytokine and chemokine gene expression. Chronic ethanol feeding significantly increased the number and size of polyps in colon of AOM/DSS treated mice. Confocal microscopic and immunoblot analyses showed a significant elevation of phospho-Smad, VEGF and HIF1α in the colonic mucosa. RT-PCR analysis at a precancerous stage indicated that ethanol significantly increases the expression of cytokines IL-1α, IL-6 and TNFα, and the chemokines CCL5/RANTES, CXCL9/MIG and CXCL10/IP-10 in the colonic mucosa of AOM/DSS treated mice. Confocal microscopy showed that ethanol feeding induces a dramatic elevation of myeloperoxidase, Gr1 and CD68-positive cells in the colonic mucosa of AOM/DSS-treated mice. Ethanol feeding enhanced AOM/DSS-induced suppression of tight junction protein expression and elevated cell proliferation marker, Ki-67 in the colonic epithelium. This study demonstrates that chronic ethanol feeding promotes colonic tumorigenesis potentially by enhancing inflammation and elevation of proinflammatory cytokines and chemokines

  13. Corticotropin-releasing hormone and mast cells in the regulation of mucosal barrier function in the human colon.

    Science.gov (United States)

    Wallon, Conny; Söderholm, Johan D

    2009-05-01

    Corticotropin-releasing hormone (CRH) is an important neuro-endocrine mediator of the stress response. Local effects of CRH in the intestinal mucosa have become evident in recent years. We showed that CRH activates CRH receptor subtypes R1 and R2 on subepithelial mast cells, thereby inducing increased transcellular uptake of protein antigens in human colonic biopsies in Ussing chambers. Ongoing studies also implicate local cholinergic signaling in regulation of macromolecular permeability in the human colon. Since increased uptake of antigenic molecules is associated with mucosal inflammation, our findings may have implications for understanding stress-related intestinal disorders.

  14. Development and Improvement of Simple Colonic Mucosal Ulcer during Treatment of Severe Ulcerative Colitis with Tacrolimus

    Directory of Open Access Journals (Sweden)

    Ayumi Ito

    2017-03-01

    Full Text Available Diarrhea, melena, and lower abdominal pain developed in a male in his 20s and colonoscopy showed pancolitis-type severe ulcerative colitis (UC. Treatment was initiated with 4,000 mg of 5-aminosalicylic acid and 60 mg/day of prednisolone, but the symptoms and inflammatory reaction worsened with prednisolone dose reduction. Tacrolimus was added to the treatment, which subsequently induced remission. Serial colonoscopies during the treatment showed improvement in ulcer and mucosal edema throughout the entire large intestine, but a new solitary round ulcer appeared at the end of the ileum. Since no signs of Behçet’s disease were noted, it was considered as a simple ulcer, a complication of UC. Tacrolimus treatment was continued based on continued improvement in clinical features and colonic mucosa, excluding the end of the ileum. Colonoscopy at 6 months after initiation of tacrolimus showed healing of the large intestinal mucosa, although mild congestion was still noted. The solitary round ulcer at the end of the ileum improved to a small erosion. We report the improvement of a simple ulcer that developed during tacrolimus treatment.

  15. Colonization and effector functions of innate lymphoid cells in mucosal tissues

    Science.gov (United States)

    Kim, Myunghoo; Kim, Chang H.

    2016-01-01

    Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID:27365193

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

    Science.gov (United States)

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

    2015-01-01

    We have previously shown that high-protein (HP) diet ingestion causes marked changes in the luminal environment of the colonic epithelium. This study aimed to evaluate the impact of such modifications on small intestinal and colonic mucosa, two segments with different transit time and physiological functions. Rats were fed with either normal protein (NP; 14% protein) or HP (53% protein) isocaloric diet for 2 weeks, and parameters related to intestinal mucous-secreting cells and to several innate/adaptive immune characteristics (myeloperoxidase activity, cytokine and epithelial TLR expression, proportion of immune cells in gut-associated lymphoid tissues) were measured in the ileum and colon. In ileum from HP animals, we observed hyperplasia of mucus-producing cells concomitant with an increased expression of Muc2 at both gene and protein levels, reduction of mucosal myeloperoxidase activity, down-regulation of Tlr4 gene expression in enterocytes and down-regulation of mucosal Th cytokines associated with CD4+ lymphocyte reduction in mesenteric lymph nodes. These changes coincided with an increased amount of acetate in the ileal luminal content. In colon, HP diet ingestion resulted in a lower number of goblet cells at the epithelial surface but increased goblet cell number in colonic crypts together with an increased Muc3 and a slight reduction of Il-6 gene expression. Our data suggest that HP diet modifies the goblet cell distribution in colon and, in ileum, increases goblet cell activity and decreases parameters related to basal gut inflammatory status. The impact of HP diet on intestinal mucosa in terms of beneficial or deleterious effects is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Colonic transit time is related to bacterial metabolism and mucosal turnover in the human gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

    Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic t...... imply a healthy gut microbial ecosystem and points at colonic transit time as a highly important factor to consider in microbiome and metabolomics studies.......Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic...... transit time and the gut microbial composition and metabolism, we assessed the colonic transit time of 98 subjects using radiopaque markers, and profiled their gut microbiota by16S rRNA gene sequencing and their urine metabolome by ultra performance liquid chromatography mass spectrometry. Based...

  18. Genome-wide Gene Expression Analysis of Mucosal Colonic Biopsies and Isolated Colonocytes Suggests a Continuous Inflammatory State in the Lamina Propria of Patients with Quiescent Ulcerative Colitis

    DEFF Research Database (Denmark)

    Bjerrum, Jacob Tveiten; Hansen, Morten; Olsen, Jørgen

    2010-01-01

    colonocytes from UC patients and controls in order to identify the cell types responsible for the continuous inflammatory state. Methods: Adjacent mucosal colonic biopsies were obtained endoscopically from the descending colon in patients with active UC (n = 8), quiescent UC (n = 9), and with irritable bowel......Background: Genome-wide gene expression (GWGE) profiles of mucosal colonic biopsies have suggested the existence of a continuous inflammatory state in quiescent ulcerative colitis (UC). The aim of this study was to use DNA microarray-based GWGE profiling of mucosal colonic biopsies and isolated......-discriminant analysis using the SIMCA-P 11 software (Umetrics, Umea, Sweden). Results: A clear separation between active UC, quiescent UC, and control biopsies were found, whereas the model for the colonocytes was unable to distinguish between quiescent UC and controls. The differentiation between quiescent UC...

  19. Colonization and effector functions of innate lymphoid cells in mucosal tissues.

    Science.gov (United States)

    Kim, Myunghoo; Kim, Chang H

    2016-10-01

    Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  20. Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

    2016-01-01

    Little is known about how colonic transit time relates to human colonic metabolism and its importance for host health, although a firm stool consistency, a proxy for a long colonic transit time, has recently been positively associated with gut microbial richness. Here, we show that colonic transi...... does not per se imply a healthy gut microbial ecosystem and points at colonic transit time as a highly important factor to consider in microbiome and metabolomics studies.......Little is known about how colonic transit time relates to human colonic metabolism and its importance for host health, although a firm stool consistency, a proxy for a long colonic transit time, has recently been positively associated with gut microbial richness. Here, we show that colonic transit...... time in humans, assessed using radio-opaque markers, is associated with overall gut microbial composition, diversity and metabolism. We find that a long colonic transit time associates with high microbial richness and is accompanied by a shift in colonic metabolism from carbohydrate fermentation...

  1. Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation

    OpenAIRE

    Chaloner, A.; Rao, A.; Al-Chaer, E.D.; Meerveld, B. Greenwood-Van

    2009-01-01

    Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liqui...

  2. A High Grain Diet Dynamically Shifted the Composition of Mucosa-Associated Microbiota and Induced Mucosal Injuries in the Colon of Sheep

    Directory of Open Access Journals (Sweden)

    Yue Wang

    2017-10-01

    Full Text Available This study investigated the dynamic shifts in mucosa-associated microbiota composition and mucosal morphology in the colon of sheep fed a high grain (HG diet. A total of 20 male sheep were randomly assigned to four groups (n = 5 for each. The sheep in first group received hay diet. The animals in other 3 groups were fed an HG diet for 7 (HG7, 14 (HG14, or 28 (HG28 days, respectively. Colonic digesta samples were collected to determine the pH and the concentrations of volatile fatty acid (VFA and lactate. The colonic mucosa was sampled to characterize the bacterial communities using Illumina MiSeq sequencing and to determine mRNA expression levels of cytokines and tight junction protein genes using quantitative real-time PCR. As time advanced, results revealed that colonic pH linearly decreased (P = 0.007, and the concentrations of total VFA linearly increased (P < 0.001. Microbial analysis showed that an HG diet linearly reduced (P < 0.050 the diversity and richness of the colonic microbiota. The principal coordinate analysis results showed that the colonic mucosa-associated bacterial communities of the four groups significantly shifted with number of days fed an HG diet. At the genus level, HG feeding significantly increased the relative abundance of some taxa including Prevotella, Coprococcus, Roseburia, and Clostridium_sensu_stricto_1, and decreased the proportion of Treponema, and the percentage of these taxa was not affected by days fed an HG diet. The microscopic examination showed that HG feeding caused the mucosal epithelial injury. The RT-PCR results showed that the mRNA expression of claudin-1 (P = 0.038, IL-1β (P = 0.045, IL-6 (P = 0.050, and TNF-α (P = 0.020 increased linearly with number of days fed an HG diet. The correlation analysis revealed significant correlation between the colonic mucosal mRNA expression of cytokines and mucosal bacterial composition. Generally, HG feeding increased colonic fermentation and altered colonic

  3. Colonic transit time relates to bacterial metabolism and mucosal turnover in the human gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

    catabolism as reflected by microbial metabolites in urine. This results in a number of potentially deleterious protein-derived metabolites. Additionally, longer colonic transit time correlates with metabolites likely reflecting reduced renewal of the colonic mucosa. Together, this suggests that a high gut...

  4. Space environmental factor impacts upon murine colon microbiota and mucosal homeostasis

    Data.gov (United States)

    National Aeronautics and Space Administration — We report how high and low linear energy transfer (LET) radiation microgravity and elevated dietary iron affect colon microbiota (determined by 16S rDNA...

  5. Navy and black bean supplementation primes the colonic mucosal microenvironment to improve gut health.

    Science.gov (United States)

    Monk, Jennifer M; Lepp, Dion; Wu, Wenqing; Pauls, K Peter; Robinson, Lindsay E; Power, Krista A

    2017-11-01

    Common beans (Phaseolus vulgaris L.) are enriched in non-digestible fermentable carbohydrates and phenolic compounds that can modulate the colonic microenvironment (microbiota and host epithelial barrier) to improve gut health. In a comprehensive assessment of the impact of two commonly consumed bean varieties (differing in levels and types of phenolic compounds) within the colonic microenvironment, C57Bl/6 mice were fed diets supplemented with 20% cooked navy bean (NB) or black bean (BB) flours or an isocaloric basal diet control (BD) for 3 weeks. NB and BB similarly altered the fecal microbiota community structure (16S rRNA sequencing) notably by increasing the abundance of carbohydrate fermenting bacteria such as Prevotella, S24-7 and Ruminococcus flavefaciens, which coincided with enhanced short chain fatty acid (SCFA) production (microbial-derived carbohydrate fermentation products) and colonic expression of the SCFA receptors GPR-41/-43/-109a. Both NB and BB enhanced multiple aspects of mucus and epithelial barrier integrity vs. BD including: (i) goblet cell number, crypt mucus content and mucin mRNA expression, (ii) anti-microbial defenses (Reg3γ), (iii) crypt length and epithelial cell proliferation, (iv) apical junctional complex components (occludin, JAM-A, ZO-1 and E-cadherin) mRNA expression and (v) reduced serum endotoxin concentrations. Interestingly, biomarkers of colon barrier integrity (crypt height, mucus content, cell proliferation and goblet cell number) were enhanced in BB vs. NB-fed mice, suggesting added benefits attributable to unique BB components (e.g., phenolics). Overall, NB and BB improved baseline colonic microenvironment function by altering the microbial community structure and activity and promoting colon barrier integrity and function; effects which may prove beneficial in attenuating gut-associated diseases. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  6. The effect of sennosides on colonic mucosal histology and bowel preparation

    NARCIS (Netherlands)

    van Gorkom, B A; Karrenbeld, A; Limburg, A J; Kleibeuker, J H

    Introduction: A single high dose of sennosides is often used to optimize bowel preparation for diagnostic procedures. From previous studies it is suspected that sennosides in such a dose cause acute damage to the colonic mucosa. This study was designed to determine any effects of sennosides on

  7. Colonic mucosal changes in Egyptian patients with liver cirrhosis and portal hypertension

    Directory of Open Access Journals (Sweden)

    Zakaria A Salama

    2013-01-01

    Conclusion The prevalence of PHC and haemorrhoids increases with the progression of liver disease and worsening of the Child-Pugh grading in cirrhotic patients. However, haemorrhoids, rectal varices, hyperaemia and colonic angiodysplasia are not affected by the presence of portal hypertensive gastropathy.

  8. Specific modulation of mucosal immune response, tolerance and proliferation in mice colonized with A. muciniphila

    NARCIS (Netherlands)

    Derrien, M.M.N.; Baarlen, van Peter; Hooiveld, Guido; Norin, Elisabeth; Muller, Michael; Vos, de Willem

    2011-01-01

    Epithelial cells of the mammalian intestine are covered with a mucus layer that prevents direct contact with intestinal microbes but also constitutes a substrate for mucus-degrading bacteria. To study the effect of mucus degradation on the host response, germ-free mice were colonized with

  9. Quantitative evaluation of the safety of mucosal incision and submucosal dissection for colon during endoscopic submucosal dissection using carbon dioxide laser

    Science.gov (United States)

    Noguchi, Takuma; Honda, Norihiro; Hazama, Hisanao; Morita, Yoshinori; Awazu, Kunio

    2018-02-01

    Since the increase in the overall mortality rate in patients with colon cancer is remarkably high in recent years, early treatment is required. For this reason, endoscopic submucosal dissection (ESD) has been at the forefront of international attention as a low invasive treatment for early digestive cancer. In current ESD procedure, an electrosurgical knife is used for mucosal incision and subsequent submucosal dissection. However, the perforation has been reported to occur by approximately 5%. Thus, to enhance the tissue selectivity of this modality, we focused on the application of laser for ESD. A carbon dioxide laser was chosen as a surgical knife because the saline or a sodium hyaluronate solution injected into the submucosal layer in current ESD procedure has a high absorption coefficient at the wavelength of the carbon dioxide laser. In this research, ex vivo experiment was performed at the output power of 3-7 W and discuss the optimum irradiation power of laser. As a result of ex vivo experiment using extracted porcine colon tissues, mucosal incision and submucosal dissection were safely and less invasively performed in every output power, without reaching the thermal damage to a muscular layer. This is because a carbon dioxide laser is strongly absorbed by saline injected into submucosa. ESD using a carbon dioxide laser is a safer method for the treatment of early colon cancer. We are planning to measure and compare the optical and thermal properties of porcine colon with those of human colon.

  10. Overexpression of GRß in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease.

    Science.gov (United States)

    Nagy, Zsolt; Acs, Bence; Butz, Henriett; Feldman, Karolina; Marta, Alexa; Szabo, Peter M; Baghy, Kornelia; Pazmany, Tamas; Racz, Karoly; Liko, Istvan; Patocs, Attila

    2016-01-01

    The glucocorticoid receptor (GR) plays a crucial role in inflammatory responses. GR has several isoforms, of which the most deeply studied are the GRα and GRß. Recently it has been suggested that in addition to its negative dominant effect on GRα, the GRß may have a GRα-independent transcriptional activity. The GRß isoform was found to be frequently overexpressed in various autoimmune diseases, including inflammatory bowel disease (IBD). In this study, we wished to test whether the gene expression profile found in a GRß overexpressing intestinal cell line (Caco-2GRß) might mimic the gene expression alterations found in patients with IBD. Whole genome microarray analysis was performed in both normal and GRß overexpressing Caco-2 cell lines with and without dexamethasone treatment. IBD-related genes were identified from a meta-analysis of 245 microarrays available in online microarray deposits performed on intestinal mucosa samples from patients with IBD and healthy individuals. The differentially expressed genes were further studied using in silico pathway analysis. Overexpression of GRß altered a large proportion of genes that were not regulated by dexamethasone suggesting that GRß may have a GRα-independent role in the regulation of gene expression. About 10% of genes differentially expressed in colonic mucosa samples from IBD patients compared to normal subjects were also detected in Caco-2 GRß intestinal cell line. Common genes are involved in cell adhesion and cell proliferation. Overexpression of GRß in intestinal cells may affect appropriate mucosal repair and intact barrier function. The proposed novel role of GRß in intestinal epithelium warrants further studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The size, morphology, site, and access score predicts critical outcomes of endoscopic mucosal resection in the colon.

    Science.gov (United States)

    Sidhu, Mayenaaz; Tate, David J; Desomer, Lobke; Brown, Gregor; Hourigan, Luke F; Lee, Eric Y T; Moss, Alan; Raftopoulos, Spiro; Singh, Rajvinder; Williams, Stephen J; Zanati, Simon; Burgess, Nicholas; Bourke, Michael J

    2018-01-25

    The SMSA (size, morphology, site, access) polyp scoring system is a method of stratifying the difficulty of polypectomy through assessment of four domains. The aim of this study was to evaluate the ability of SMSA to predict critical outcomes of endoscopic mucosal resection (EMR). We retrospectively applied SMSA to a prospectively collected multicenter database of large colonic laterally spreading lesions (LSLs) ≥ 20 mm referred for EMR. Standard inject-and-resect EMR procedures were performed. The primary end points were correlation of SMSA level with technical success, adverse events, and endoscopic recurrence. 2675 lesions in 2675 patients (52.6 % male) underwent EMR. Failed single-session EMR occurred in 124 LSLs (4.6 %) and was predicted by the SMSA score ( P  < 0.001). Intraprocedural and clinically significant postendoscopic bleeding was significantly less common for SMSA 2 LSLs (odds ratio [OR] 0.36, P  < 0.001 and OR 0.23, P  < 0.01) and SMSA 3 LSLs (OR 0.41, P  < 0.001 and OR 0.60, P  = 0.05) compared with SMSA 4 lesions. Similarly, endoscopic recurrence at first surveillance was less likely among SMSA 2 (OR 0.19, P  < 0.001) and SMSA 3 (OR 0.33, P  < 0.001) lesions compared with SMSA 4 lesions. This also extended to second surveillance among SMSA 4 LSLs. SMSA is a simple, readily applicable, clinical score that identifies a subgroup of patients who are at increased risk of failed EMR, adverse events, and adenoma recurrence at surveillance colonoscopy. This information may be useful for improving informed consent, planning endoscopy lists, and developing quality control measures for practitioners of EMR, with potential implications for EMR benchmarking and training. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Specialist Endoscopists Are Associated with a Decreased Risk of Incomplete Polyp Resection During Endoscopic Mucosal Resection in the Colon.

    Science.gov (United States)

    Tavakkoli, Anna; Law, Ryan J; Bedi, Aarti O; Prabhu, Anoop; Hiatt, Tadd; Anderson, Michelle A; Wamsteker, Erik J; Elmunzer, B Joseph; Piraka, Cyrus R; Scheiman, James M; Elta, Grace H; Kwon, Richard S

    2017-09-01

    Endoscopic experience is known to correlate with outcomes of endoscopic mucosal resection (EMR), particularly complete resection of the polyp tissue. Whether specialist endoscopists can protect against incomplete polypectomy in the setting of known risk factors for incomplete resection (IR) is unknown. We aimed to characterize how specialist endoscopists may help to mitigate the risk of IR of large sessile polyps. This is a retrospective cohort study of patients who underwent EMR at the University of Michigan from January 1, 2006, to November 15, 2015. The primary outcome was endoscopist-reported polyp tissue remaining at the end of the initial EMR attempt. Specialist endoscopists were defined as endoscopists who receive tertiary referrals for difficult colonoscopy cases and completed at least 20 EMR colonic polyp resections over the study period. A total of 257 patients with 269 polyps were included in the study. IR occurred in 40 (16%) cases. IR was associated with polyp size ≥ 40 mm [adjusted odds ratio (aOR) 3.31, 95% confidence interval (CI) 1.38-7.93], flat/laterally spreading polyps (aOR 2.61, 95% CI 1.24-5.48), and difficulty lifting the polyp (aOR 11.0, 95% CI 2.66-45.3). A specialist endoscopist performing the initial EMR was protective against IR, even in the setting of risk factors for IR (aOR 0.13, 95% CI 0.04-0.41). IR is associated with polyp size ≥ 40 mm, flat and/or laterally spreading polyps, and difficulty lifting the polyp. A specialist endoscopist initiating the EMR was protective of IR.

  13. Antioxidant Activity of Inulin and Its Role in the Prevention of Human Colonic Muscle Cell Impairment Induced by Lipopolysaccharide Mucosal Exposure

    Science.gov (United States)

    Guarino, Michele Pier Luca; Locato, Vittoria; Cocca, Silvia; Cimini, Sara; Palma, Rossella; Alloni, Rossana; De Gara, Laura; Cicala, Michele

    2014-01-01

    Background Fructans, such as inulin, are dietary fibers which stimulate gastro-intestinal (GI) function acting as prebiotics. Lipopolysaccharide (LPS) impairs GI motility, through production of reactive oxygen species. The antioxidant activity of various fructans was tested and the protective effect of inulin on colonic smooth muscle cell (SMC) impairment, induced by exposure of human mucosa to LPS, was assessed in an ex vivo experimental model. Methods The antioxidant capacity of fructans was measured in an in vitro system that simulates cooking and digestion processes. Human colonic mucosa and submucosa, obtained from disease-free margins of resected segments for cancer, were sealed between two chambers, with the mucosal side facing upwards with Krebs solution with or without purified LPS from a pathogenic strain of Escherichia coli (O111:B4) and inulin (Frutafit IQ), and the submucosal side facing downwards into Krebs solution. The solutions on the submucosal side were collected following mucosal exposure to Krebs in the absence (N-undernatant) or presence of LPS (LPS-undernatant) or LPS+inulin (LPS+INU-undernatant). Undernatants were tested for their antioxidant activity and the effects on SMCs contractility. Inulin protective effects on mucosa and submucosa layers were assessed measuring the protein oxidation level in the experimental conditions analyzed. Results Antioxidant activity of inulin, which was significantly higher compared to simple sugars, remained unaltered despite cooking and digestion processes. Inulin protected the mucosal and submucosal layers against protein oxidation. Following exposure to LPS-undernatant, a significant decrease in maximal acetylcholine (Ach)-induced contraction was observed when compared to the contraction induced in cells incubated with the N-undernatant (4±1% vs 25±5% respectively, PInulin (35±5%). Conclusions Inulin protects the human colon mucosa from LPS-induced damage and this effect appears to be related to the

  14. Impact of Dietary Galacto-Oligosaccharide (GOS) on Chicken’s Gut Microbiota, Mucosal Gene Expression, and Salmonella Colonization

    OpenAIRE

    Rebecca-Ayme Hughes; Rebecca-Ayme Hughes; Riawana A. Ali; Mary A. Mendoza; Hosni M. Hassan; Matthew D. Koci

    2017-01-01

    Preventing Salmonella colonization in young birds is key to reducing contamination of poultry products for human consumption (eggs and meat). While several Salmonella vaccines have been developed that are capable of yielding high systemic antibodies, it is not clear how effective these approaches are at controlling or preventing Salmonella colonization of the intestinal tract. Effective alternative control strategies are needed to help supplement the bird’s ability to prevent Salmonella colon...

  15. Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn's Disease in Treatment-Naive Pediatric Patients.

    Science.gov (United States)

    Rosen, Michael J; Karns, Rebekah; Vallance, Jefferson E; Bezold, Ramona; Waddell, Amanda; Collins, Margaret H; Haberman, Yael; Minar, Phillip; Baldassano, Robert N; Hyams, Jeffrey S; Baker, Susan S; Kellermayer, Richard; Noe, Joshua D; Griffiths, Anne M; Rosh, Joel R; Crandall, Wallace V; Heyman, Melvin B; Mack, David R; Kappelman, Michael D; Markowitz, James; Moulton, Dedrick E; Leleiko, Neal S; Walters, Thomas D; Kugathasan, Subra; Wilson, Keith T; Hogan, Simon P; Denson, Lee A

    2017-05-01

    There is controversy regarding the role of the type 2 immune response in the pathogenesis of ulcerative colitis (UC)-few data are available from treatment-naive patients. We investigated whether genes associated with a type 2 immune response in the intestinal mucosa are up-regulated in treatment-naive pediatric patients with UC compared with patients with Crohn's disease (CD)-associated colitis or without inflammatory bowel disease (IBD), and whether expression levels are associated with clinical outcomes. We used a real-time reverse-transcription quantitative polymerase chain reaction array to analyze messenger RNA (mRNA) expression patterns in rectal mucosal samples from 138 treatment-naive pediatric patients with IBD and macroscopic rectal disease, as well as those from 49 children without IBD (controls), enrolled in a multicenter prospective observational study from 2008 to 2012. Results were validated in real-time reverse-transcription quantitative polymerase chain reaction analyses of rectal RNA from an independent cohort of 34 pediatric patients with IBD and macroscopic rectal disease and 17 controls from Cincinnati Children's Hospital Medical Center. We measured significant increases in mRNAs associated with a type 2 immune response (interleukin [IL]5 gene, IL13, and IL13RA2) and a type 17 immune response (IL17A and IL23) in mucosal samples from patients with UC compared with patients with colon-only CD. In a regression model, increased expression of IL5 and IL17A mRNAs distinguished patients with UC from patients with colon-only CD (P = .001; area under the receiver operating characteristic curve, 0.72). We identified a gene expression pattern in rectal tissues of patients with UC, characterized by detection of IL13 mRNA, that predicted clinical response to therapy after 6 months (odds ratio [OR], 6.469; 95% confidence interval [CI], 1.553-26.94), clinical response after 12 months (OR, 6.125; 95% CI, 1.330-28.22), and remission after 12 months (OR, 5

  16. Antioxidant activity of inulin and its role in the prevention of human colonic muscle cell impairment induced by lipopolysaccharide mucosal exposure.

    Directory of Open Access Journals (Sweden)

    Valentina Pasqualetti

    Full Text Available BACKGROUND: Fructans, such as inulin, are dietary fibers which stimulate gastro-intestinal (GI function acting as prebiotics. Lipopolysaccharide (LPS impairs GI motility, through production of reactive oxygen species. The antioxidant activity of various fructans was tested and the protective effect of inulin on colonic smooth muscle cell (SMC impairment, induced by exposure of human mucosa to LPS, was assessed in an ex vivo experimental model. METHODS: The antioxidant capacity of fructans was measured in an in vitro system that simulates cooking and digestion processes. Human colonic mucosa and submucosa, obtained from disease-free margins of resected segments for cancer, were sealed between two chambers, with the mucosal side facing upwards with Krebs solution with or without purified LPS from a pathogenic strain of Escherichia coli (O111:B4 and inulin (Frutafit IQ, and the submucosal side facing downwards into Krebs solution. The solutions on the submucosal side were collected following mucosal exposure to Krebs in the absence (N-undernatant or presence of LPS (LPS-undernatant or LPS+inulin (LPS+INU-undernatant. Undernatants were tested for their antioxidant activity and the effects on SMCs contractility. Inulin protective effects on mucosa and submucosa layers were assessed measuring the protein oxidation level in the experimental conditions analyzed. RESULTS: Antioxidant activity of inulin, which was significantly higher compared to simple sugars, remained unaltered despite cooking and digestion processes. Inulin protected the mucosal and submucosal layers against protein oxidation. Following exposure to LPS-undernatant, a significant decrease in maximal acetylcholine (Ach-induced contraction was observed when compared to the contraction induced in cells incubated with the N-undernatant (4±1% vs 25±5% respectively, P<0.005 and this effect was completely prevented by pre-incubation of LPS with Inulin (35±5%. CONCLUSIONS: Inulin protects

  17. Microscopic Colitis Evolved Into Inflammatory Bowel Diseases Is Characterized by Increased Th1/Tc1 Cells in Colonic Mucosal Lamina Propria.

    Science.gov (United States)

    Li, Ji; Yan, Yuchu; Meng, Ziran; Liu, Shuhong; Beck, Paul L; Ghosh, Subrata; Qian, Jiaming; Gui, Xianyong

    2017-10-01

    An association between microscopic colitis (MC), i.e., lymphocytic colitis (LC) and collagenous colitis (CC), and inflammatory bowel diseases (IBD) has been noticed. A subset of MC cases may evolve into IBD, and IBD in remission may present as MC in a histologic pattern. Moreover, MC and IBD may coexist in different regions of the bowel. A link between MC and IBD in their pathogenesis is, therefore, suggested. Abnormal mucosal immunity is likely the key. We reviewed 2324 MC cases in Calgary over 14 years and identified 20 cases evolved into IBD (IBD transformers). 13 of them were further investigated for colonic mucosal lamina propria mononuclear cells (LPMNCs), as opposed to 22 cases whose MC resolved. On their index colonic biopsy immunohistochemistry was performed to detect major T cell subsets characterized by key cytokines and master transcription factors (IFNγ and T-bet for Th1/Tc1, GATA-3 for Th2/Tc2, IL-17 and RORc for Th17/Tc17, FoxP3 for Treg/Tcreg) as well as TNFα + cells (partly representing Th1). LPMNCs positive for each marker were counted (average number per high-power field). IBD transformers had increased IFNγ + , T-bet + , TNF-α + , and GATA-3 + LPMNCs compared to the MC-resolved cases. The LC-to-IBD subgroup had increased IFNγ + and GATA-3 + cells compared to the LC-resolved subgroup. The CC-to-IBD subgroup had increased T-bet + , TNF-α + , and GATA-3 + cells compared to the CC-resolved subgroup. Among MC-resolved patients, more TNF-α + and RORc + cells were seen in LC than in CC. Th1/Tc1- and TNFα-producing cells, and likely a subset of Th2/Tc2 cells as well, may be involved in the MC-to-IBD transformation.

  18. White and dark kidney beans reduce colonic mucosal damage and inflammation in response to dextran sodium sulfate.

    Science.gov (United States)

    Monk, Jennifer M; Zhang, Claire P; Wu, Wenqing; Zarepoor, Leila; Lu, Jenifer T; Liu, Ronghua; Pauls, K Peter; Wood, Geoffrey A; Tsao, Rong; Robinson, Lindsay E; Power, Krista A

    2015-07-01

    Common beans are a rich source of nondigestible fermentable components and phenolic compounds that have anti-inflammatory effects. We assessed the gut-health-promoting potential of kidney beans in healthy mice and their ability to attenuate colonic inflammation following dextran sodium sulphate (DSS) exposure (via drinking water, 2% DSS w/v, 7 days). C57BL/6 mice were fed one of three isocaloric diets: basal diet control (BD), or BD supplemented with 20% cooked white (WK) or dark red kidney (DK) bean flour for 3 weeks. In healthy mice, anti-inflammatory microbial-derived cecal short chain fatty acid (SCFA) levels (acetate, butyrate and propionate), colon crypt height and colonic Mucin 1 (MUC1) and Resistin-like Molecule beta (Relmβ) mRNA expression all increased in WK- and DK-fed mice compared to BD, indicative of enhanced microbial activity, gut barrier integrity and antimicrobial defense response. During colitis, both bean diets reduced (a) disease severity, (b) colonic histological damage and (c) increased mRNA expression of antimicrobial and barrier integrity-promoting genes (Toll-like Receptor 4 (TLR4), MUC1-3, Relmβ and Trefoil Factor 3 (TFF3)) and reduced proinflammatory mediator expression [interleukin (IL)-1β, IL-6, interferon (IFN)γ, tumor necrosis factor (TNF)α and monocyte chemoattractant protein-1], which correlated with reduced colon tissue protein levels. Further, bean diets exerted a systemic anti-inflammatory effect during colitis by reducing serum levels of IL-17A, IFNγ, TNFα, IL-1β and IL-6. In conclusion, both WK and DK bean-supplemented diets enhanced microbial-derived SCFA metabolite production, gut barrier integrity and the microbial defensive response in the healthy colon, which supported an anti-inflammatory phenotype during colitis. Collectively, these data demonstrate a beneficial colon-function priming effect of bean consumption that mitigates colitis severity. Crown Copyright © 2015. Published by Elsevier Inc. All rights

  19. Relationships between body mass index and short-circuit current in human duodenal and colonic mucosal biopsies. Osbak PS, Bindslev N, Hansen MB. Acta Physiol (Oxf). 2011 Jan;201(1):47-53

    DEFF Research Database (Denmark)

    Osbak, Philip Samuel; Bindslev, Niels; Berner-Hansen, Mark

    2011-01-01

    Aim: Retrospectively, to investigate the relationship between body mass index (BMI) and basal electrogenic transport as measured by short-circuit current (SCC) in human duodenal and colonic mucosal biopsies. Methods: The study included biopsies from mucosa of normal appearance in the sigmoid colon...... and >25 kg m)2). Statistical significance was assessed by the unpaired t-test or Wilcoxon rank-sum test. Correlation coefficients were calculated by Pearson product moment correlation. Results: In colonic biopsies, basal SCC (mean standard deviation) was significantly higher in 59 biopsies from 30...

  20. Efficient and reproducible identification of mismatch repair deficient colon cancer

    DEFF Research Database (Denmark)

    Joost, Patrick; Bendahl, Pär-Ola; Halvarsson, Britta

    2013-01-01

    BACKGROUND: The identification of mismatch-repair (MMR) defective colon cancer is clinically relevant for diagnostic, prognostic and potentially also for treatment predictive purposes. Preselection of tumors for MMR analysis can be obtained with predictive models, which need to demonstrate ease...... of application and favorable reproducibility. METHODS: We validated the MMR index for the identification of prognostically favorable MMR deficient colon cancers and compared performance to 5 other prediction models. In total, 474 colon cancers diagnosed ≥ age 50 were evaluated with correlation between...... clinicopathologic variables and immunohistochemical MMR protein expression. RESULTS: Female sex, age ≥60 years, proximal tumor location, expanding growth pattern, lack of dirty necrosis, mucinous differentiation and presence of tumor-infiltrating lymphocytes significantly correlated with MMR deficiency. Presence...

  1. Human α-amylase present in lower-genital-tract mucosal fluid processes glycogen to support vaginal colonization by Lactobacillus.

    Science.gov (United States)

    Spear, Gregory T; French, Audrey L; Gilbert, Douglas; Zariffard, M Reza; Mirmonsef, Paria; Sullivan, Thomas H; Spear, William W; Landay, Alan; Micci, Sandra; Lee, Byung-Hoo; Hamaker, Bruce R

    2014-10-01

    Lactobacillus colonization of the lower female genital tract provides protection from the acquisition of sexually transmitted diseases, including human immunodeficiency virus, and from adverse pregnancy outcomes. While glycogen in vaginal epithelium is thought to support Lactobacillus colonization in vivo, many Lactobacillus isolates cannot utilize glycogen in vitro. This study investigated how glycogen could be utilized by vaginal lactobacilli in the genital tract. Several Lactobacillus isolates were confirmed to not grow in glycogen, but did grow in glycogen-breakdown products, including maltose, maltotriose, maltopentaose, maltodextrins, and glycogen treated with salivary α-amylase. A temperature-dependent glycogen-degrading activity was detected in genital fluids that correlated with levels of α-amylase. Treatment of glycogen with genital fluids resulted in production of maltose, maltotriose, and maltotetraose, the major products of α-amylase digestion. These studies show that human α-amylase is present in the female lower genital tract and elucidates how epithelial glycogen can support Lactobacillus colonization in the genital tract. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Proteome stability analysis of snap frozen, RNAlater preserved, and formalin-fixed paraffin-embedded human colon mucosal biopsies

    Directory of Open Access Journals (Sweden)

    Tue Bjerg Bennike

    2016-03-01

    Full Text Available Large repositories of well characterized RNAlater preserved samples and formalin-fixed, paraffin-embedded samples have been generated worldwide. However, the impact on the proteome of the preservation methods remain poorly described. Therefore, we analyzed the impact on the proteome of preserving samples in RNAlater, and by formalin-fixation, paraffin-embedding on human soft tissue, using directly frozen samples as a control (“Comparing the proteome of snap frozen, RNAlater preserved, and formalin-fixed paraffin-embedded human tissue samples” [1]. We here report the data from the analysis. The comparative analysis was performed on 24 colon mucosa biopsies, extracted from the sigmoideum of two gastroenterologically healthy participants for the purpose of this study. A set of biopsies were additionally stored for 30 min at room temperature prior to formalin-fixation. The samples were analyzed by high throughput gel free quantitative proteomics. The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PRIDE: http://www.ebi.ac.uk/pride/archive/projects/PXD002029. Keywords: Human, Colon, Mucosa, RNAlater, FFPE, Snap-frozen, Stability, LC–MS, Proteomics

  3. Evaluation of CD40 and CD80 receptors in the colonic mucosal membrane of children with inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Barbara Kamińska

    2015-12-01

    Full Text Available [b][/b][b]Introduction. [/b]The most prevalent inflammatory bowel diseases (IBD include ulcerative colitis (UC and Crohn’s disease (CD. Immune processes play a vital role in the etiopathogenesis of these conditions, involving both cellular and humoral response mechanisms. The aim of this study was to quantify CD40- and CD80-positive cells in the biopsy specimens of large intestinal mucosa from children with IBD. [b]Materials and method. [/b]The study comprised 38 children aged between 3–17 years (mean 11.5±3.7 years – 20 boys (52.6 % and 18 girls (47.4%. Eighteen patients were diagnosed with UC on the basis of clinical manifestation, endoscopic and histopathological findings. Mean age of this subgroup was 11.55±4.07 years. A group of 10 children (mean age 12.30±2.83 diagnosed with CD was also included. The control group comprised 10 IBD-free children (mean age 10.28±4.07 years. The surface expressions of CD40 and CD80 were analyzed in large intestine mucosa biopsy specimens, fixed in formaldehyde, embedded in paraffin, and cut with a microtome into 4 µm slices. [b]Results. [/b]The number of CD40- and CD80-positive cells in the large intestinal mucosa of children with Crohn’s disease and ulcerative colitis was significantly higher than in the controls. The highest number of CD40+ and CD80+ cells was observed in the caecal mucosal membrane of Crohn’s disease patients and in the rectal mucosa of individuals with ulcerative colitis. [b]Conclusion.[/b] IBD is characterized by elevated, segment-specific, expression of CD40 and CD80.

  4. [Efficiency of autogenous training in medical rehabilitation of patients with irritable colon syndrome with constipation dominance].

    Science.gov (United States)

    Pakhomova, I V; Aĭvazian, T A; Zaĭtsev, V P; Gusakova, E V; Molina, L P

    2008-01-01

    It was established that use of autogenous training makes possible to increase efficiency of the therapy, leading to considerable more evident improvement of somatic and psychotic state, decrease of pain syndrome. Predictors of efficiency of autogenous training were marked out. Indications for use the method in medical rehabilitation of patients with irritable colon syndrome with constipation dominance were elaborated.

  5. Bacterium-like Particles for efficient immune stimulation of existing vaccines and new subunit vaccines in mucosal applications

    Directory of Open Access Journals (Sweden)

    Natalija eVan Braeckel-Budimir

    2013-09-01

    Full Text Available The successful development of a mucosal vaccine critically depends on the use of a safe and effective immunostimulant and/or carrier system. This review describes the effectiveness and mode of action of an immunostimulating particle derived from bacteria in mucosal subunit vaccines. The non-living particles, designated Bacterium-like Particles (BLPs are based on the food-grade bacterium Lactococcus lactis. The focus of the overview is on the development of intranasal BLP-based vaccines to prevent diseases caused by influenza and respiratory syncytial virus, and includes a selection of Phase I clinical data for the intranasal FluGEM vaccine.

  6. Altered colonic mucosal Polyunsaturated Fatty Acid (PUFA derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology.

    Directory of Open Access Journals (Sweden)

    Mojgan Masoodi

    Full Text Available Ulcerative colitis (UC is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids within the inflammatory milieu in UC. We hypothesised that severity of inflammation is associated with alteration of lipid mediators, in relapsing UC.Study was case-control design. Mucosal lipid mediators were determined by LC-MS/MS lipidomics analysis on mucosal biopsies taken from patients attending outpatients with relapsing UC. Univariate and multivariate statistical analyses were used to investigate the association of mucosal lipid mediators, with the disease state and severity graded histologically.Levels of PGE2, PGD2, TXB2, 5-HETE, 11-HETE, 12-HETE and 15-HETE are significantly elevated in inflamed mucosa and correlate with severity of inflammation, determined using validated histological scoring systems.Our approach of capturing inflammatory mediator signature at different stages of UC by combining comprehensive lipidomics analysis and computational modelling could be used to classify and predict mild-moderate inflammation; however, predictive index is diminished in severe inflammation. This new technical approach could be developed to tailor drug treatments to patients with active UC, based on the mucosal lipid mediator profile.

  7. Comparison of Mucosal, Subcutaneous and Intraperitoneal Routes of Rat Leptospira Infection

    Science.gov (United States)

    Zilber, Anne-Laure; Belli, Patrick; Grezel, Delphine; Artois, Marc; Kodjo, Angeli; Djelouadji, Zoheira

    2016-01-01

    Leptospirosis is a zoonosis found worldwide that is caused by a spirochete. The main reservoirs of Leptospira, which presents an asymptomatic infection, are wild rodents, including the brown rat (Rattus norvegicus). Experimental studies of the mechanisms of its renal colonization in rats have previously used an intraperitoneal inoculation route. However, knowledge of rat-rat transmission requires the use of a natural route of inoculation, such as a mucosal or subcutaneous route. We investigated for the first time the effects of subcutaneous and mucosal inoculation routes compared to the reference intraperitoneal route during Leptospira infection in adult rats. Infection characteristics were studied using Leptospira renal isolation, serology, and molecular and histological analyses. Leptospira infection was asymptomatic using each inoculation route, and caused similar antibody production regardless of renal colonization. The observed renal colonization rates were 8 out of 8 rats, 5 out of 8 rats and 1 out of 8 rats for the intraperitoneal, mucosal and subcutaneous inoculation routes, respectively. Thus, among the natural infection routes studied, mucosal inoculation was more efficient for renal colonization associated with urinary excretion than the subcutaneous route and induced a slower-progressing infection than the intraperitoneal route. These results can facilitate understanding of the infection modalities in rats, unlike the epidemiological studies conducted in wild rats. Future studies of other natural inoculation routes in rat models will increase our knowledge of rat-rat disease transmission and allow the investigation of infection kinetics. PMID:27031867

  8. Mucosal expression of basic fibroblastic growth factor, Syndecan 1 and tumor necrosis factor-alpha in diverticular disease of the colon: a case-control study.

    Science.gov (United States)

    Tursi, A; Elisei, W; Brandimarte, G; Giorgetti, G M; Inchingolo, C D; Nenna, R; Picchio, M; Giorgio, F; Ierardi, E

    2012-09-01

    Inflammation may be detected in diverticular disease (DD), and fibrosis may also develop. We assessed the mucosal expression of bFGF, SD1, and TNF-α in DD according to the severity of the disease. Moreover, we assessed the response to therapy of these cytokines in acute uncomplicated diverticulitis (AUD). Fifteen patients affected by AUD and seven patients affected by symptomatic uncomplicated diverticular disease (SUDD) were enrolled. Patients with asymptomatic diverticulosis (AD), segmental colitis associated with diverticulosis (SCAD), ulcerative colitis (UC), and healthy subjects (HC) served as control groups. The expression of bFGF, SD1, and TNF-α was significantly higher in diverticulitis than in healthy controls, in diverticulosis, and in uncomplicated diverticular disease. Cytokines were significantly higher in uncomplicated diverticular disease than in healthy controls. Cytokine expression in diverticulitis did not differ significantly from that of ulcerative colitis. After treatment, TNF-α expression dropped significantly. Mucosal TNF-α is overexpressed only in symptomatic DD, while SD1 and bFGF are already overexpressed in AD. Finally, TNF-α but not SD1 or bFGF expression seems to be influenced by the treatment in AUD. © 2012 Blackwell Publishing Ltd.

  9. Local oral immunization with synthetic peptides induces a dual mucosal IgG and salivary IgA antibody response and prevents colonization of Streptococcus mutans.

    Science.gov (United States)

    Lehner, T; Haron, J; Bergmeier, L A; Mehlert, A; Beard, R; Dodd, M; Mielnik, B; Moore, S

    1989-01-01

    A small cell surface antigen of Streptococcus mutans was partially sequenced and the amino terminal peptides of 11, 15 and 20 amino acid residues and a dimer of the 15 and 20 residues peptides were synthesized. The synthetic peptides (SP) were used in topical oral immunization of the gingivomucosal epithelium of macaque monkeys. Sequential examination for antibodies over a period of up to 30 weeks revealed that six applications of the linear or cyclized SP11 and a random SP11 induced negligible or very low antibody levels. In contrast, the SP17 (SP15 with added cysteine at each terminus), SP21 (SP20 with one cysteine) and the dimer (SP35) induced significant anti-SP as well as anti-native streptococcal antibodies in the gingival fluid and in saliva. The functional significance of this immune response was examined by studying its effect on oral colonization of S. mutans following feeding of a carbohydrate-rich diet. Whereas control animals, sham-immunized with a random SP of 11 residues, showed increased colonization of the teeth by S. mutans, there was no colonization or a significant reduction in colonization of animals immunized with the cyclized SP17, linear SP21 or dimerized SP35. These experiments suggest that local immunization with SP derived from the sequences of a streptococcal cell surface antigen induce a dual local immune response of gingival IgG and salivary IgA antibodies against the SP and native SA. These antibodies may be involved in preventing colonization of S. mutans, which is the principal agent in the development of dental caries. PMID:2759661

  10. Efficient intracellular delivery of 5-fluorodeoxyuridine into colon cancer cells by targeted immunoliposomes

    NARCIS (Netherlands)

    Koning, GA; Kamps, JAAM; Scherphof, GL

    2002-01-01

    Immunoliposomes, liposomes with monoclonal antibodies attached, are being developed for targeting the anti-cancer drug 5-fluoro-2'-deoxyuridine (FUdR) to colon cancer cells. A monoclonal antibody against the rat colon carcinoma CC531 was covalently coupled to liposomes containing a dipalmitoylated

  11. Influence of the particle size of activated charcoal on labeling efficiency with 67Ga-citrate for colonic transit study

    International Nuclear Information System (INIS)

    Wan-Yu Lin; Shih-Chuan Tsai; Kai-Yuan Cheng; Bor-Tsung Hsieh

    2008-01-01

    Indium-111 and 99m Tc have been proposed for colonic transit study, but 111 In is expensive and the half-life of 99m Tc is too short for the study. Gallium-67 citrate is inexpensive and has a suitable half-life. In our previous study, we successfully labeled 67 Ga-citrate activated charcoal, and the labeling efficiency exceeded 91% after a 96 hour incubation period. In this work, we evaluated the influence of the size of activated charcoal particles on the labeling efficiency with 67 Ga-citrate. The data showed that the influence of particle size on the labeling efficiency of activated charcoal with 67 Ga was insignificant. Both sizes of activated charcoal particles can be used for labeling with 67 Ga in colonic transit study. (author)

  12. Mucosal healing in ulcerative colitis

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Coskun, Mehmet; Nielsen, Ole Haagen

    2013-01-01

    . With the introduction of the tumor necrosis factor-alpha inhibitors for the treatment of UC, it has become increasingly evident that the disease course is influenced by whether or not the patient achieves mucosal healing. Thus, patients with mucosal healing have fewer flare-ups, a decreased risk of colectomy......, and a lower probability of developing colorectal cancer. Understanding the mechanisms of mucosal wound formation and wound healing in UC, and how they are affected therapeutically is therefore of importance for obtaining efficient treatment strategies holding the potential of changing the disease course of UC....... This review is focused on the pathophysiological mechanism of mucosal wound formation in UC as well as the known mechanisms of intestinal wound healing. Regarding the latter topic, pathways of both wound healing intrinsic to epithelial cells and the wound-healing mechanisms involving interaction between...

  13. Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue

    Directory of Open Access Journals (Sweden)

    K.P. Nickerson

    2018-05-01

    Full Text Available Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and “mini-guts,” organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies. Keywords: Typhoid fever, Salmonella, Snapwell™ system, Human tissue, Terminal ileum, Immune system, Innate immunity, Immune evasion, Host-pathogen interaction, Vaccine development, Intestinal organoids, Organoid monolayer

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

    Science.gov (United States)

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

    2015-04-01

    Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  15. Effects of synbiotics on intestinal mucosal barrier in rat model

    Directory of Open Access Journals (Sweden)

    Zhigang Xue

    2017-06-01

    Conclusions: Probiotics can improve the concentration of colonic probiotics, while synbiotics can improve probiotics concentration and mucosa thickness in colon, decrease L/M ratio and bacterial translocation. Synbiotics shows more protective effects on intestinal mucosal barrier in rats after cecectomy and gastrostomy and the intervention of specific antibiotics.

  16. Mucosal vaccines: recent progress in understanding the natural barriers.

    Science.gov (United States)

    Borges, Olga; Lebre, Filipa; Bento, Dulce; Borchard, Gerrit; Junginger, Hans E

    2010-02-01

    It has long been known that protection against pathogens invading the organism via mucosal surfaces correlates better with the presence of specific antibodies in local secretions than with serum antibodies. The most effective way to induce mucosal immunity is to administer antigens directly to the mucosal surface. The development of vaccines for mucosal application requires antigen delivery systems and immunopotentiators that efficiently facilitate the presentation of the antigen to the mucosal immune system. This review provides an overview of the events within mucosal tissues that lead to protective mucosal immune responses. The understanding of those biological mechanisms, together with knowledge of the technology of vaccines and adjuvants, provides guidance on important technical aspects of mucosal vaccine design. Not being exhaustive, this review also provides information related to modern adjuvants, including polymeric delivery systems and immunopotentiators.

  17. Colon cancer

    Science.gov (United States)

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma; Colon carcinoma ... eat may play a role in getting colon cancer. Colon cancer may be linked to a high-fat, ...

  18. Undecylprodigiosin conjugated monodisperse gold nanoparticles efficiently cause apoptosis in colon cancer cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Nikodinovic-Runic, Jasmina; Mojic, Marija; Kang, Yijin; Maksimovic-Ivanic, Danijela; Mijatovic, Sanja; Vasiljevic, Branka; Stamenkovic, Vojislav R.; Senerovic, Lidija

    2014-01-01

    Bacterial pigment undecylprodigiosin (UP) was produced using Streptomyces sp. JS520 and conjugated to monodisperse gold nanoparticles (UP-Au). Both UP and UP-Au showed cytocidal activity towards melanoma (A375), lung carcinoma (A549), breast cancer (MCF-7) and colon cancer (HCT-116) cells, inducing apoptosis with IC50 values ranging from 0.4 to 4 mu g ml(-1). Unconjugated UP had a tendency to lose its activity over time and to change biophysical characteristics over pH. The loss of the pigment potency was overcome by conjugation with gold nanoparticles. UP-Au exhibited high stability over pH 3.8 to 7.4 and its activity remained unaffected in time. Nano-packing changed the mechanism of UP toxicity by converting the intracellular signals from a mitochondrial dependent to a mitochondrial independent apoptotic process. The availability of nonpyrogenic UP in high amounts, together with specific anticancer activity and improved stability in the complex with gold nanoparticles, presents a novel platform for further development of UP-Au complexes as an anticancer drug suitable for clinical applications.

  19. Complicated colonic intussusception

    Directory of Open Access Journals (Sweden)

    Justin James

    2012-01-01

    Full Text Available The manuscript deals with the case of a 53-year-old woman who developed large bowel obstruction. Per-rectal examination revealed a pedunculated lesion in the rectum; rigid sigmoidoscopy revealed a prolapsing pedunculated mass with a necrotic surface. The patient recovered well following anterior resection. Histology confirmed a pedunculated sub mucosal lipoma as the lead point for intussusception. Colonic intussusception is a rare cause of adult large bowel obstruction, and the preoperative clinical diagnosis of this condition can be difficult. Resection of the involved segment of the colon is the most appropriate choice of treatment in most such cases.

  20. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

    Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

  1. Histological study of the left colon of rats after extra-mucosal seromyotomy (continent valves: evaluation of colonic emptying Estudo histológico do cólon esquerdo de ratos após a confecção de seromiotomias extra-mucosas (válvulas continentes: avaliação do grau de esvaziamento do conteúdo colônico

    Directory of Open Access Journals (Sweden)

    Beatriz Deoti

    2008-06-01

    Full Text Available PURPOSE: To elaborate an animal model with the objective of studying the continence of the biological valves surgically performed in the left colon of rats. METHODS: Thirty four rats were operated on and divided into three groups (G. G1 (sham animals which underwent laparotomy only; G2 (perineal amputation without valves: animals which underwent amputation of the anal sphincter complex combined with a perineal colostomy; G3 (abdominoperineal amputation combined with valves: animals which underwent abdominoperineal amputation combined with three, equidistant and circumferential (360(0, extra-mucosal seromyotomies, of the descending colon, which were sutured to create biological valves combined with perineal colostomy. Animals were euthanized in the late postoperative period and surgical valves were saved for histopathological study. RESULTS: Surgical procedure provoked intestinal dilation, as well as segmented chambers along the descending colon. Retained fecalomas between the valves and proximal to them were also noted. Six rats died of intestinal obstruction due to fecal impaction at the surgical site. The sequence of events was: stasis, obstruction, distention, perforation, peritonitis and death. Histopathology showed inflammation due to foreign body type reaction around the sutured colon causing partial concentric stenosis, capable of interfering normal mechanical activity of the distal colon. This process resulted in retardation of the intestinal transit. CONCLUSION: Extra-mucosal seromyotomies, with seromuscular suture, can be used as an operative procedure capable of causing retardation in the intestinal transit of rats.OBJETIVO: Modelo de experimentação, com confecção de válvulas biológicas no cólon esquerdo de ratos com o objetivo de estudar o grau de continência dessas válvulas. MÉTODOS: Trinta e quatro ratos foram operados e distribuidos em três grupos: G1 (grupo simulado submetido apenas à laparotomia, G2 (grupo amputado

  2. Necrotizing colitis associated with carcinoma of the colon

    International Nuclear Information System (INIS)

    Woo, Seong Ku; Lim, Jae Hoon; Kim, Soon Yong; Ahn, Chi Yul

    1982-01-01

    Necrotizing colitis associated with carcinoma of the colon, known also as obstructive colitis, is a disorder characterized by anulceration and inflammation of the colon proximal to an obstructive lesion, especially carcinoma of the rectosigmoid colon, and in rare instance, leads to acute gangrene of the colon. The authors analyzed radiologic findings in four cases of necrotizing colitis associated with carcinoma of the colon. Barium enema disclosed mucosal edema, nodular filling defects, irregularity of the colonic contour and typical thumbprinting appearance of involved colon proximal to an obstructing carcinoma of the colon. The mechanism of necrotizing colitis was briefly reviewed

  3. shRNA-Mediated XRCC2 Gene Knockdown Efficiently Sensitizes Colon Tumor Cells to X-ray Irradiation in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Qin Wang

    2014-01-01

    Full Text Available Colon cancer is one of the most common tumors of the digestive tract. Resistance to ionizing radiation (IR decreased therapeutic efficiency in these patients’ radiotherapy. XRCC2 is the key protein of DNA homologous recombination repair, and its high expression is associated with enhanced resistance to DNA damage induced by IR. Here, we investigated the effect of XRCC2 silencing on colon tumor cells’ growth and sensitivity to X-radiation in vitro and in vivo. Colon tumor cells (T84 cell line were cultivated in vitro and tumors originated from the cell line were propagated as xenografts in nude mice. The suppression of XRCC2 expression was achieved by using vector-based short hairpin RNA (shRNA in T84 cells. We found that the knockdown of XRCC2 expression effectively decreased T84 cellular proliferation and colony formation, and led to cell apoptosis and cell cycle arrested in G2/M phase induced by X-radiation in vitro. In addition, tumor xenograft studies suggested that XRCC2 silencing inhibited tumorigenicity after radiation treatment in vivo. Our data suggest that the suppression of XRCC2 expression rendered colon tumor cells more sensitive to radiation therapy in vitro and in vivo, implying XRCC2 as a promising therapeutic target for the treatment of radioresistant human colon cancer.

  4. New frontiers in mucositis.

    Science.gov (United States)

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

    2012-01-01

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

  5. Probiotics as Antifungals in Mucosal Candidiasis.

    Science.gov (United States)

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

    2016-05-01

    Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  6. Neonatal mucosal immunology.

    Science.gov (United States)

    Torow, N; Marsland, B J; Hornef, M W; Gollwitzer, E S

    2017-01-01

    Although largely deprived from exogenous stimuli in utero, the mucosal barriers of the neonate after birth are bombarded by environmental, nutritional, and microbial exposures. The microbiome is established concurrently with the developing immune system. The nature and timing of discrete interactions between these two factors underpins the long-term immune characteristics of these organs, and can set an individual on a trajectory towards or away from disease. Microbial exposures in the gastrointestinal and respiratory tracts are some of the key determinants of the overall immune tone at these mucosal barriers and represent a leading target for future intervention strategies. In this review, we discuss immune maturation in the gut and lung and how microbes have a central role in this process.

  7. Aleitamento materno e colonização mucocutânea pelo Staphylococcus aureus na criança com dermatite atópica Breastfeeding and mucosal and cutaneous colonization by Staphylococcus aureus in atopic children

    Directory of Open Access Journals (Sweden)

    Raissa Massaia Londero Chemello

    2011-06-01

    remains unclear whether colonization of atopic patients by Staphylococcus aureus (S. aureus through breastfeeding is relevant to the development of AD. OBJECTIVE: To examine the potential relation between breastfeeding and colonization by S. aureus in atopic patients. METHOD: Transversal study of atopic patients, aged from 4 to 24 months, both genders, receiving outpatient care and 72 mothers. Data on infant breastfeeding practices and on clinical-epidemiological profile were registered. Swabs of the infants' nares and skin (cubital fossa and swabs of the mothers' nares were collected. For univariate analysis, X2 (chi-square and Fischer Exact's test were used. RESULTS: Among breastfed children, S. aureus was isolated from 8 (25.8% infants' nares swabs and from 4 (12.9% skin swabs. Among not breastfed children, S. aureus was isolated from 10 (20.8% infants' nares swabs and from 11 (22.9% skin swabs. Sixteen mothers (22.2% had S. aureus isolated from their nares swabs. There was no significant association between breastfeeding and S. aureus colonization (child skin and/or nares. However, there was a degree of concordance for S. aureus carriage among mothers and infants. Among 72 pairs, 56 (77.8% were concordant. CONCLUSION: Breastfeeding was not associated with S. aureus muco-cutaneous colonization in atopic infants

  8. New Pathways for Alimentary Mucositis

    Directory of Open Access Journals (Sweden)

    Joanne M. Bowen

    2008-01-01

    Full Text Available Alimentary mucositis is a major dose-limiting toxicity associated with anticancer treatment. It is responsible for reducing patient quality of life and represents a significant economic burden in oncology. The pathobiology of alimentary mucositis is extremely complex, and an increased understanding of mechanisms and pathway interactions is required to rationally design improved therapies. This review describes the latest advances in defining mechanisms of alimentary mucositis pathobiology in the context of pathway activation. It focuses particularly on the recent genome-wide analyses of regimen-related mucosal injury and the identification of specific regulatory pathways implicated in mucositis development. This review also discusses the currently known alimentary mucositis risk factors and the development of novel treatments. Suggestions for future research directions have been raised.

  9. Mucosal melanosis associated with chemoembolization

    Directory of Open Access Journals (Sweden)

    Ali Alkan

    2015-06-01

    Full Text Available Mucosal lesions due to underlying disease or drug toxicity, are important part of oncology practice. Patient with a diagnosis of hepatocellular carcinoma was treated with chemoembolisation. She presented with new onset of mucosal hyperpigmented lesion all through her oral cavity. Biopsy was consistent with mucosal melanosis, which was associated with the chemotherapeutics used in the chemoembolisation procedure. Lesion progressively improved without any treatment. Here we present an mucosal melanosis experience after chemoembolisation. J Clin Exp Invest 2015; 6 (2: 189-191

  10. Digital gastrointestinal imaging: Effect of pixel size of subtle mucosal abnormalities on observer performance

    International Nuclear Information System (INIS)

    Kastan, D.J.; Ackerman, L.V.; Feczko, P.J.

    1986-01-01

    Radiographs from double-contrast colon examinations demonstrating subtle mucosal changes of inflammatory bowel disease and radiographs showing normal colon were digitized (0.1-mm, 0.2-mm, 0.4-mm and 0.8-mm pixel sizes). Ten radiologists interpreted the laser-printed images. Receiver operating characteristic analysis was performed. The results indicated that (1) the sensitivity of radiography in detecting subtle mucosal abnormalities improved as resolution improved; (2) more experience readers performed remarkably well even at the poorer levels of resolution; (3) the resolution necessary for evaluating the colonic mucosa was less than expected; and (4) at low noise levels, conventional television fluoroscopy may have sufficient resolution for mucosal evaluation

  11. Mucosal immunity to poliovirus.

    Science.gov (United States)

    Ogra, Pearay L; Okayasu, Hiromasa; Czerkinsky, Cecil; Sutter, Roland W

    2011-10-01

    The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and Poliovirus Vaccines: Impact on Wild Poliovirus Infection, Transmission and Vaccine Failure conference was organized to obtain a better understanding of the current status of global control of poliomyelitis and identify approaches to improve the immune responsiveness and effectiveness of the orally administered poliovirus vaccines in order to accelerate the global eradication of paralytic poliomyelitis.

  12. Mucosal immunology and virology

    National Research Council Canada - National Science Library

    Tyring, Stephen

    2006-01-01

    .... A third chapter focuses on the proximal end of the gastrointestinal tract (i.e. the oral cavity). The mucosal immunology and virology of the distal end of the gastrointestinal tract is covered in the chapter on the anogenital mucosa. Mucosa-associated lymphoid tissue (MALT) plays a role in protection against all viral (and other) infections except those that enter the body via a bite (e.g. yellow fever or dengue from a mosquito or rabies from a dog) or an injection or transfusion (e.g. HIV, Hepatitis B). ...

  13. Rectal mucosal electrosensitivity - what is being tested?

    Science.gov (United States)

    Meagher, A P; Kennedy, M L; Lubowski, D Z

    1996-01-01

    The results of rectal mucosal electrosensitivity (RME) testing have been used to support theories regarding the aetiology of both idiopathic constipation and bowel dysfunction following rectopexy. The aim of this study was to assess the validity of tests of RME. Sixty-eight patients, comprising three groups (group 1: 50 patients undergoing assessment in the Anorectal Physiology Unit, group 2: 10 patients with coloanal or ileoanal anastomosis, group 3: 8 patients with a stoma) underwent mucosal electrosensitivity testing, with the threshold stimulus required to elicit sensation being recorded. In addition the RME was measured in groups 1 and 2 when placing the electrode, mounted on a catheter with a central wire, against the anterior, posterior, right and left rectal or neorectal walls. To asses the influence on this test of loss of mucosal contact due to faeces, a further 8 cases with a normal rectum had RME performed with and without a layer of water soaked gauze around the electrode to stimulate faeces and prevent the electrode from making contact with the rectal mucosa. There was marked variance in the sensitivity of the different regions of rectal wall tested (P < 0.001). In group 1 patients the mean sensitivities were: central 36.6 mA, anterior 27.4 mA, posterior 37.9 mA, right 22.3 mA and left 25.6 mA. This circumferential variation suggests that the pelvic floor rather than rectal mucosa was being stimulated. All patients in group 2 had recordable sensitivities, and the mean sensitivity threshold was significantly higher than group 1 patients in the central (P = 0.03), right (P = 0.03) and left (P = 0.007) positions. In group 3 the sensitivity was greater within the stoma at the level of the abdominal wall muscle than intra-abdominally or subcutaneously, again suggesting an extra-colonic origin of the sensation. The sensitivity threshold was significantly greater with the electrode wrapped in gauze (P < 0.01), and loss of mucosal contact was not detected by

  14. Thiolated carboxymethyl dextran as a nanocarrier for colon delivery of hSET1 antisense: In vitro stability and efficiency study

    International Nuclear Information System (INIS)

    Kiani, Melika; Mirzazadeh Tekie, Farnaz Sadat; Dinarvand, Meshkat; Soleimani, Masoud; Dinarvand, Rassoul; Atyabi, Fatemeh

    2016-01-01

    Gene therapy is an optimistic approach in cancer treatment. However, for efficient delivery of gene materials, designing an appropriate vector is necessary. Polyelectrolyte complexes (PECs) of chitosan and dextran could be considered a proper nanoparticulate carrier for sensitive biomaterials. In this study, PECs of chitosan and thiolated dextran were used as either an injectable or oral gene delivery system. hSET1 antisense was loaded into the PECs to suppress proliferation of colon cancer cell line. The prepared nanoparticles have ~ 115 nm diameter size and positive zeta potential with high mucoadhesion properties. They are able to protect antisense from degradation in serum and biorelevant fluids (FaSSIF and FaSSGF). Furthermore, prepared nanoparticles demonstrated superior cellular penetration and inhibitory effect on SW480 colon cancer cell proliferation. All nanoparticles significantly down regulated hSET1 in comparison with naked antisense. It can be concluded that thiolated PECs have potential use for injectable or oral delivery of nucleic acids such as antisense. - Highlights: • Formation of stable nanoparticle with dextran and chitosan derivatives for oral and intravenous gene delivery. • Satifactory cellular uptake of nanoparticles and approximately complete suppression of hSET1 expression in SW480 cell lines • Prolonged stability of nanoparticles against biorelevent media with desirable release rate.

  15. Thiolated carboxymethyl dextran as a nanocarrier for colon delivery of hSET1 antisense: In vitro stability and efficiency study

    Energy Technology Data Exchange (ETDEWEB)

    Kiani, Melika, E-mail: Melika.kiani@gmail.com [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Mirzazadeh Tekie, Farnaz Sadat, E-mail: mirzazadehf@yahoo.com [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Dinarvand, Meshkat, E-mail: mdinarvand@hotmail.com [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Soleimani, Masoud, E-mail: soleim_m@modares.ac.ir [Stem Cell Technology Research Centre, P.O. Box 14155-3174, Tehran (Iran, Islamic Republic of); Department of Hematology, School of Medical Sciences, Tarbiat Modares University, P.O. Box: 14115-111, Tehran (Iran, Islamic Republic of); Dinarvand, Rassoul, E-mail: dinarvand@tums.ac.ir [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Atyabi, Fatemeh, E-mail: atyabifa@tums.ac.ir [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2016-05-01

    Gene therapy is an optimistic approach in cancer treatment. However, for efficient delivery of gene materials, designing an appropriate vector is necessary. Polyelectrolyte complexes (PECs) of chitosan and dextran could be considered a proper nanoparticulate carrier for sensitive biomaterials. In this study, PECs of chitosan and thiolated dextran were used as either an injectable or oral gene delivery system. hSET1 antisense was loaded into the PECs to suppress proliferation of colon cancer cell line. The prepared nanoparticles have ~ 115 nm diameter size and positive zeta potential with high mucoadhesion properties. They are able to protect antisense from degradation in serum and biorelevant fluids (FaSSIF and FaSSGF). Furthermore, prepared nanoparticles demonstrated superior cellular penetration and inhibitory effect on SW480 colon cancer cell proliferation. All nanoparticles significantly down regulated hSET1 in comparison with naked antisense. It can be concluded that thiolated PECs have potential use for injectable or oral delivery of nucleic acids such as antisense. - Highlights: • Formation of stable nanoparticle with dextran and chitosan derivatives for oral and intravenous gene delivery. • Satifactory cellular uptake of nanoparticles and approximately complete suppression of hSET1 expression in SW480 cell lines • Prolonged stability of nanoparticles against biorelevent media with desirable release rate.

  16. Multiscale modeling of mucosal immune responses

    Science.gov (United States)

    2015-01-01

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

  17. Multiscale modeling of mucosal immune responses.

    Science.gov (United States)

    Mei, Yongguo; Abedi, Vida; Carbo, Adria; Zhang, Xiaoying; Lu, Pinyi; Philipson, Casandra; Hontecillas, Raquel; Hoops, Stefan; Liles, Nathan; Bassaganya-Riera, Josep

    2015-01-01

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

  18. Helicobacter bilis Infection Alters Mucosal Bacteria and Modulates Colitis Development in Defined Microbiota Mice.

    Science.gov (United States)

    Atherly, Todd; Mosher, Curtis; Wang, Chong; Hostetter, Jesse; Proctor, Alexandra; Brand, Meghan W; Phillips, Gregory J; Wannemuehler, Michael; Jergens, Albert E

    2016-11-01

    Helicobacter bilis infection of C3H/HeN mice harboring the altered Schaedler flora (ASF) triggers progressive immune responsiveness and the development of colitis. We sought to investigate temporal alterations in community structure of a defined (ASF-colonized) microbiota in normal and inflamed murine intestines and to correlate microbiota changes to histopathologic lesions. The colonic mucosal microbiota of healthy mice and ASF mice colonized with H. bilis for 3, 6, or 12 weeks were investigated by fluorescence in situ hybridization targeting the 16S ribosomal RNA genes of total bacteria, group-specific organisms, and individual ASF bacterial species. Microbial profiling of ASF and H. bilis abundance was performed on cecal contents. Helicobacter bilis-colonized mice developed colitis associated with temporal changes in composition and spatial distribution of the mucosal microbiota. The number of total bacteria, ASF519, and helicobacter-positive bacteria were increased (P attachment, or by invasion, and this interaction is differentially expressed over time.

  19. Oral Candida as an aggravating factor of mucositis Induced by radiotherapy

    International Nuclear Information System (INIS)

    Simoes, Cristiane Araujo; Castro, Jurema Freire Lisboa de; Cazal, Claudia

    2011-01-01

    Antineoplastic treatment induces some undesirable consequences in head and neck cancer patients. Often, the emergence of major clinical manifestations, such as oral mucositis, results in temporary interruption of the treatment, decreasing the patients' quality of life, and increasing hospital costs. Radio-induced or chemo-induced oral mucositis is possibly aggravated by opportunist fungal infections, which turn the mucositis more resistant to the conventional treatments. Objective: this study aims to identify the presence of Candida sp. as a possible aggravating factor of oral mucositis in patients with head and neck cancer under antineoplastic treatment. Method: all patients with radio- or chemo-induced oral mucositis from the Cancer Hospital of Pernambuco, treated between October 2008 and April 2009, were selected for the study. The prevalence of Candida sp was measured through the cytological analysis of oral mucosa in patients with oral mucositis. The fungal presence was correlated with the mucositis severity. Results: the results showed a positive association between fungal colonization and more several lesions (degrees III and IV of mucositis). Conclusion: The outcomes shown may contribute to a solution for unconventional mucosites, which do not respond to the usual treatment. (author)

  20. Colon interposition

    International Nuclear Information System (INIS)

    Isolauri, J.; Tampere Univ. Central Hospital; Paakkala, T.; Arajaervi, P.; Markkula, H.

    1987-01-01

    Colon interposition was carried out in 12 patients with oesophageal carcinoma and on 38 patients with benign oesophageal disease an average of 71 months before the radiographic examination. Various ischaemic changes including 'jejunization', loss of haustration and stricture formation were observed in 15 cases. In 12 patients one or several diverticula were seen in the colon graft. Reflux was observed in 17 cases in supine position. Double contrast technique in the examination of interposed colon is recommended. (orig.)

  1. Role of helminths in regulating mucosal inflammation.

    Science.gov (United States)

    Weinstock, Joel V; Summers, Robert W; Elliott, David E

    2005-09-01

    The rapid rise in prevalence of ulcerative colitis (UC) and Crohn's disease (CD) in highly developed countries suggests that environmental change engenders risk for inflammatory bowel disease (IBD). Eradication of parasitic worms (helminths) through increased hygiene may be one such change that has led to increased prevalence of these diseases. Helminths alter host mucosal and systemic immunity, inhibiting dysregulated inflammatory responses. Animals exposed to helminths are protected from experimental colitis, encephalitis, and diabetes. Patients with CD or UC improve when exposed to whipworm. Lamina propria (LP) mononuclear cells from helminth-colonized mice make less interleukin (IL)-12 p40 and IFN-gamma, but more IL-4, IL-13, IL-10, TGF-beta, and PGE(2) compared to LP mononuclear cells from naive mice. Systemic immune responses show similar skewing toward Th2 and regulatory cytokine production in worm-colonized animal models and humans. Recent reports suggest that helminths induce regulatory T cell activity. These effects by once ubiquitous organisms may have protected individuals from many of the emerging immune-mediated illnesses like IBD, multiple sclerosis, type I diabetes, and asthma.

  2. Cutaneous and mucosal pain syndromes

    Directory of Open Access Journals (Sweden)

    Siddappa K

    2002-01-01

    Full Text Available The cutaneous and mucosal pain syndromes are characterized by pain, burning sensation, numbness or paraesthesia of a particular part of the skin or mucosal surface without any visible signs. They are usually sensory disorders, sometimes with a great deal of psychologic overlay. In this article various conditions have been listed and are described. The possible causative mechanisms are discussed when they are applicable and the outline of their management is described.

  3. Endoscopic mucosal resection for early gastric cancer. A case report.

    Science.gov (United States)

    Gheorghe, Cristian; Sporea, Ioan; Becheanu, Gabriel; Gheorghe, Liana

    2002-03-01

    European experience in endoscopic mucosal resection (EMR) for early gastric cancer is still relatively low, since early stomach cancer is diagnosed at a much lower rate in Europe than in Japan and generally operable patients are referred to surgery for radical resection. Endoscopic mucosal resection or mucosectomy was developed as a promising technology to diagnose and treat mucosal lesions in the esophagus, stomach and colon. In contrast to surgical resection, EMR allows "early cancers" to be removed with a minimal cost, morbidity and mortality. We present the case of a patient with hepatic cirrhosis incidentally diagnosed with an elevated-type IIa early gastric cancer. Echoendoscopy was performed in order to assess the depth of invasion into the gastric wall confirming the only mucosal involvement. We performed an EMR using "cup and suction" method. After the procedure, the patient experienced an acute upper gastrointestinal bleeding from the ulcer bed requiring argon plasma coagulation. The histopathological examination confirmed an early cancer, without involvement of muscularis mucosae. The patient has had an uneventful evolution being well at six months after the procedure

  4. Irradiation mucositis and oral flora

    International Nuclear Information System (INIS)

    Spijkervet, F.K.L.

    1989-01-01

    This study, which is motivated by the substantial morbidity of local signs of mucositis and generalized symptoms that result from mucositis induced by therapeutic irradiation, has the following objectives: To investigate if it is possible to prevent irradiation mucositis via oral flora elimination, and, if it is true that flora plays a role in irradiation mucositis, what fraction of the oral flora may be involved; to evaluate oral Gram-negative bacillary carriage; to investigate the possibility to eradicate Gram-negative bacilli from the oral cavity; to evaluate oral yeast carriage; to investigate the possibility to eradicate yeasts stomatitis and the 'selectivity' of elimination of flora. Two methods are described for monitoring alterations of mucositis of the oral cavity and changes in oral flora. Chlorhexidine has been tested as the commonly used prophylaxis. The effect of chlorhexidine 0.1% rinses on oral flora and mucositis has been studied in a prospective placebo controlled double blind randomized programme. The results of the influence of saliva on the antimicrobial activity of chlorhexidine and the results of selective elimination of oral flora in irradiated patients who have head and neck cancer are reported. Salivary inactivation of the topical antimicrobials used for selective elimination of oral flora has been studied and the results are reported. Finally, the objectives that have been achieved (or not) are delineated. The significance of the results of the study are discussed in terms of published information and further lines of research are suggested. (author). 559 refs.; 29 figs.; 20 tabs

  5. Colonic lipoma

    International Nuclear Information System (INIS)

    Siddiqui, M.S.; Khatri, A.R.; Quraishy, M.S.; Fatima, L.; Muzaffar, S.

    2003-01-01

    Lipoma of the colon is rare and may lead to intestinal obstruct. We have presented two cases of colonic lipoma. Both were elderly females, one presented with diarrhea and the other with sub-acute intestinal obstruction. After colonoscopy surgical removal was done. Histopathology revealed lipoma. (author)

  6. Colonic angiodysplasia

    International Nuclear Information System (INIS)

    Vallee, C.; Legmann, P.; Garnier, T.; Levesque, M.

    1984-01-01

    The main clinical, endoscopic and radiographic findings in thirty documented cases of colonic angiodysplasia or vacular ectasia are described. We emphasise the association with colonic diverticulosis and cardiovascular pathology, describe the histological changes, summarize the present physiopathological hypothesis, and consider the various therapeutic approaches. (orig.)

  7. Colonic locomotion

    NARCIS (Netherlands)

    Dodou, D.

    2006-01-01

    The most effective screening method for colonic cancer is colonoscopy. However, colonoscopy cannot be easily embraced by the population because of the related pain intensity. Robotic devices that pull themselves forward through the colon are a possible alternative. The main challenge for such

  8. MUCOSITIS PREVENTION BY SELECTIVE ELIMINATION OF ORAL FLORA IN IRRADIATED HEAD AND NECK-CANCER PATIENTS

    NARCIS (Netherlands)

    SPIJKERVET, FKL; VANSAENE, HKF; VANSAENE, JJM; PANDERS, AK; VERMEY, A; MEHTA, DM

    1990-01-01

    Mucositis induced by irradiation is the reactive inflammatory-like process of the oropharyngeal mucous membranes following irradiation. Bacteria colonizing the oral tissues are thought to contribute to this inflammatory process. The eradication of Gram-negative bacilli (selective elimination of oral

  9. Complete colonic duplication in children.

    Science.gov (United States)

    Khaleghnejad Tabari, Ahmad; Mirshemirani, Alireza; Khaleghnejad Tabari, Nasibeh

    2012-01-01

    Complete colonic duplication is a very rare congenital anomaly that may have different presentations according to its location and size. Complete colonic duplication can occur in 15% of gastrointestinal duplication. We report two cases of complete colonic duplications, and their characteristics. We present two patients with complete colonic duplication with different types and presentations. Case 1: A 2- year old boy presented to the clinic with abdominal protrusion, difficulty to defecate, chronic constipation and mucosal prolaps covered bulging (rectocele) since he was 6 months old. The patient had palpable pelvic mass with doughy consistency. Rectal exam confirmed perirectal mass with soft consistency. The patient underwent a surgical operation that had total tubular colorectal duplication with one blind end and was treated with simple fenestration of distal end, and was discharged without complication. After two years follow up, he had normal defecation and good weight gain. Case 2: A 2 -day old infant was referred with imperforate anus and complete duplication of recto-sigmoid colon, diphallus, double bladder, and hypospadiasis. After clinical and paraclinical investigations, he underwent operations in several stages in different periods, and was discharged without complications. After four years follow up, he led a normal life. The patients with complete duplication have to be examined carefully because of the high incidence of other systemic anomalies. Treatment includes simple resection of distal common wall, fenestration, and repair other associated anomalies.

  10. Inside the mucosal immune system.

    Directory of Open Access Journals (Sweden)

    Jerry R McGhee

    Full Text Available An intricate network of innate and immune cells and their derived mediators function in unison to protect us from toxic elements and infectious microbial diseases that are encountered in our environment. This vast network operates efficiently by use of a single cell epithelium in, for example, the gastrointestinal (GI and upper respiratory (UR tracts, fortified by adjoining cells and lymphoid tissues that protect its integrity. Perturbations certainly occur, sometimes resulting in inflammatory diseases or infections that can be debilitating and life threatening. For example, allergies in the eyes, skin, nose, and the UR or digestive tracts are common. Likewise, genetic background and environmental microbial encounters can lead to inflammatory bowel diseases (IBDs. This mucosal immune system (MIS in both health and disease is currently under intense investigation worldwide by scientists with diverse expertise and interests. Despite this activity, there are numerous questions remaining that will require detailed answers in order to use the MIS to our advantage. In this issue of PLOS Biology, a research article describes a multi-scale in vivo systems approach to determine precisely how the gut epithelium responds to an inflammatory cytokine, tumor necrosis factor-alpha (TNF-α, given by the intravenous route. This article reveals a previously unknown pathway in which several cell types and their secreted mediators work in unison to prevent epithelial cell death in the mouse small intestine. The results of this interesting study illustrate how in vivo systems biology approaches can be used to unravel the complex mechanisms used to protect the host from its environment.

  11. Colon neoplasm

    International Nuclear Information System (INIS)

    Kimura F, K.

    1991-01-01

    The main aspects of colon neoplasms are described, including several factors that predispose the disease, the occurrence, the main biomedical radiography and the evaluation after the surgery. (C.G.C.)

  12. Spaceflight influences both mucosal and peripheral cytokine production in PTN-Tg and wild type mice.

    Directory of Open Access Journals (Sweden)

    Justin L McCarville

    Full Text Available Spaceflight is associated with several health issues including diminished immune efficiency. Effects of long-term spaceflight on selected immune parameters of wild type (Wt and transgenic mice over-expressing pleiotrophin under the human bone-specific osteocalcin promoter (PTN-Tg were examined using the novel Mouse Drawer System (MDS aboard the International Space Station (ISS over a 91 day period. Effects of this long duration flight on PTN-Tg and Wt mice were determined in comparison to ground controls and vivarium-housed PTN-Tg and Wt mice. Levels of interleukin-2 (IL-2 and transforming growth factor-beta1 (TGF-β1 were measured in mucosal and systemic tissues of Wt and PTN-Tg mice. Colonic contents were also analyzed to assess potential effects on the gut microbiota, although no firm conclusions could be made due to constraints imposed by the MDS payload and the time of sampling. Spaceflight-associated differences were observed in colonic tissue and systemic lymph node levels of IL-2 and TGF-β1 relative to ground controls. Total colonic TGF-β1 levels were lower in Wt and PTN-Tg flight mice in comparison to ground controls. The Wt flight mouse had lower levels of IL-2 and TGF-β1 compared to the Wt ground control in both the inguinal and brachial lymph nodes, however this pattern was not consistently observed in PTN-Tg mice. Vivarium-housed Wt controls had higher levels of active TGF-β1 and IL-2 in inguinal lymph nodes relative to PTN-Tg mice. The results of this study suggest compartmentalized effects of spaceflight and on immune parameters in mice.

  13. Eosinophils express muscarinic receptors and corticotropin-releasing factor to disrupt the mucosal barrier in ulcerative colitis.

    Science.gov (United States)

    Wallon, Conny; Persborn, Mats; Jönsson, Maria; Wang, Arthur; Phan, Van; Lampinen, Maria; Vicario, Maria; Santos, Javier; Sherman, Philip M; Carlson, Marie; Ericson, Ann-Charlott; McKay, Derek M; Söderholm, Johan D

    2011-05-01

    Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropin-releasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers ((51)Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), α-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection.

    Directory of Open Access Journals (Sweden)

    Andrew Leber

    Full Text Available Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17 effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions.

  15. Dual oxidase in mucosal immunity and host-microbe homeostasis.

    Science.gov (United States)

    Bae, Yun Soo; Choi, Myoung Kwon; Lee, Won-Jae

    2010-07-01

    Mucosal epithelia are in direct contact with microbes, which range from beneficial symbionts to pathogens. Accordingly, hosts must have a conflicting strategy to combat pathogens efficiently while tolerating symbionts. Recent progress has revealed that dual oxidase (DUOX) plays a key role in mucosal immunity in organisms that range from flies to humans. Information from the genetic model of Drosophila has advanced our understanding of the regulatory mechanism of DUOX and its role in mucosal immunity. Further investigations of DUOX regulation in response to symbiotic or non-symbiotic bacteria and the in vivo consequences in host physiology will give a novel insight into the microbe-controlling system of the mucosa. Copyright 2010 Elsevier Ltd. All rights reserved.

  16. Immunology of Gut Mucosal Vaccines

    Science.gov (United States)

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

    2011-01-01

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

  17. Cryptogenic pyogenic liver abscess as the herald of colon cancer.

    Science.gov (United States)

    Jeong, Soung Won; Jang, Jae Young; Lee, Tae Hee; Kim, Hyun Gun; Hong, Sung Wook; Park, Seung Hoon; Kim, Sang Gyune; Cheon, Young Koog; Kim, Young Seok; Cho, Young Deok; Kim, Jin-Oh; Kim, Boo Sung; Lee, Eun Jung; Kim, Tae Hyong

    2012-02-01

    Colonic mucosal defects might be a route for bacterial invasion into the portal system, with subsequent hematogenous spread to the liver. We retrospectively investigated the results of colonoscopy and the clinical characteristics of patients with pyogenic liver abscess of colonic origin. A total of 230 consecutive patients with pyogenic liver abscess were reviewed between 2003 and 2010. The 230 patients were categorized into three groups (pancreatobiliary [n = 135], cryptogenic [n = 81], and others [n = 14]). Of the 81 cryptogenic patients, 37 (45.7%) underwent colonoscopy. Colonic lesions with mucosal defects were considered colonic causes of abscess. In the 37 colonoscopic investigations, colon cancer was found in six patients (16.2%), laterally-spreading tumor (LST) in two patients (5.4%), multiple colon ulcers in one patient (2.7%), colon polyps in 17 patients (45.9%), and diverticula in four patients (10.8%). Nine (11%) of 81 cryptogenic abscesses were therefore reclassified as being of colonic origin (colon cancer = 6, LST = 2, ulcer = 1). Three cases were stage III colon cancer, and the others were stage I. Two LST were high-grade dysplasia. The percentage of patients with Klebsiella pneumoniae (K. pneumoniae) and diabetes mellitus (DM) of colonic origin was 66.7%, which was significantly higher than the 8.6% for other causes (P colonic cause. Colonoscopy should be considered for the detection of hidden colonic malignant lesions in patients with cryptogenic pyogenic liver abscess, especially for patients with K. pneumoniae and DM. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  18. 14C-urea breath test as a method to detect Campylobacter pylori colonization

    NARCIS (Netherlands)

    Rauws, E. A.; van Royen, E. A.; Tytgat, G. N.

    1989-01-01

    Campylobacter pylori may cause type B gastritis. C. pylori produces urease, and the presence of this enzyme in gastric mucosal biopsies is a marker for colonization with the microorganism. The value of a breath test to detect C. pylori colonization in non-ulcer dyspepsia patients was investigated.

  19. Hypoxia inhibits colonic ion transport via activation of AMP kinase.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2012-02-01

    BACKGROUND AND AIMS: Mucosal hypoxia is a common endpoint for many pathological processes including ischemic colitis, colonic obstruction and anastomotic failure. Previous studies suggest that hypoxia modulates colonic mucosal function through inhibition of chloride secretion. However, the molecular mechanisms underlying this observation are poorly understood. AMP-activated protein kinase (AMPK) is a metabolic energy regulator found in a wide variety of cells and has been linked to cystic fibrosis transmembrane conductance regulator (CFTR) mediated chloride secretion in several different tissues. We hypothesized that AMPK mediates many of the acute effects of hypoxia on human and rat colonic electrolyte transport. METHODS: The fluorescent chloride indicator dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide was used to measure changes in intracellular chloride concentrations in isolated single rat colonic crypts. Ussing chamber experiments in human colonic mucosa were conducted to evaluate net epithelial ion transport. RESULTS: This study demonstrates that acute hypoxia inhibits electrogenic chloride secretion via AMPK mediated inhibition of CFTR. Pre-treatment of tissues with the AMPK inhibitor 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo [1,5-a] pyrimidine (compound C) in part reversed the effects of acute hypoxia on chloride secretion. CONCLUSION: We therefore suggest that AMPK is a key component of the adaptive cellular response to mucosal hypoxia in the colon. Furthermore, AMPK may represent a potential therapeutic target in diseased states or in prevention of ischemic intestinal injury.

  20. Oral Candida as an aggravating factor of mucositis Induced by radiotherapy; Candida Oral como fator agravante da mucosite radioinduzida

    Energy Technology Data Exchange (ETDEWEB)

    Simoes, Cristiane Araujo; Castro, Jurema Freire Lisboa de; Cazal, Claudia [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de odontologia

    2011-07-01

    Antineoplastic treatment induces some undesirable consequences in head and neck cancer patients. Often, the emergence of major clinical manifestations, such as oral mucositis, results in temporary interruption of the treatment, decreasing the patients' quality of life, and increasing hospital costs. Radio-induced or chemo-induced oral mucositis is possibly aggravated by opportunist fungal infections, which turn the mucositis more resistant to the conventional treatments. Objective: this study aims to identify the presence of Candida sp. as a possible aggravating factor of oral mucositis in patients with head and neck cancer under antineoplastic treatment. Method: all patients with radio- or chemo-induced oral mucositis from the Cancer Hospital of Pernambuco, treated between October 2008 and April 2009, were selected for the study. The prevalence of Candida sp was measured through the cytological analysis of oral mucosa in patients with oral mucositis. The fungal presence was correlated with the mucositis severity. Results: the results showed a positive association between fungal colonization and more several lesions (degrees III and IV of mucositis). Conclusion: The outcomes shown may contribute to a solution for unconventional mucosites, which do not respond to the usual treatment. (author)

  1. The colonic microflora and probiotic therapy in health and disease.

    LENUS (Irish Health Repository)

    Shanahan, Fergus

    2011-01-01

    Host-microbe dialogue is involved not only in maintenance of mucosal homeostasis but also in the pathogenesis of several infectious, inflammatory, and neoplastic disorders of the gut. This has led to a resurgence of interest in the colonic microbiota in health and disease. Recent landmark findings are addressed here.

  2. The Mucosal Immune System of Teleost Fish

    Directory of Open Access Journals (Sweden)

    Irene Salinas

    2015-08-01

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

  3. Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during DNA vaccination.

    Science.gov (United States)

    Holechek, Susan A; McAfee, Megan S; Nieves, Lizbeth M; Guzman, Vanessa P; Manhas, Kavita; Fouts, Timothy; Bagley, Kenneth; Blattman, Joseph N

    2016-11-04

    In order for vaccines to induce efficacious immune responses against mucosally transmitted pathogens, such as HIV-1, activated lymphocytes must efficiently migrate to and enter targeted mucosal sites. We have previously shown that all-trans retinoic acid (ATRA) can be used as a vaccine adjuvant to enhance mucosal CD8 + T cell responses during vaccination and improve protection against mucosal viral challenge. However, the ATRA formulation is incompatible with most recombinant vaccines, and the teratogenic potential of ATRA at high doses limits its usage in many clinical settings. We hypothesized that increasing in vivo production of retinoic acid (RA) during vaccination with a DNA vector expressing retinaldehyde dehydrogenase 2 (RALDH2), the rate-limiting enzyme in RA biosynthesis, could similarly provide enhanced programming of mucosal homing to T cell responses while avoiding teratogenic effects. Administration of a RALDH2- expressing plasmid during immunization with a HIVgag DNA vaccine resulted in increased systemic and mucosal CD8 + T cell numbers with an increase in both effector and central memory T cells. Moreover, mice that received RALDH2 plasmid during DNA vaccination were more resistant to intravaginal challenge with a recombinant vaccinia virus expressing the same HIVgag antigen (VACVgag). Thus, RALDH2 can be used as an alternative adjuvant to ATRA during DNA vaccination leading to an increase in both systemic and mucosal T cell immunity and better protection from viral infection at mucosal sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Gastric Mucosal Erosions - Radiologic evaluation -

    International Nuclear Information System (INIS)

    Kim, Seung Hyup

    1985-01-01

    70 cases of gastric mucosal erosions were diagnosed by double contrast upper gastrointestinal examinations and endoscopic findings. Analyzing the radiologic findings of these 70 cases of gastric mucosal erosions, the following results were obtained. 1. Among the total 70 cases, 65 cases were typical varioliform erosions showing central depressions and surrounding mucosal elevations. Remaining 5 cases were erosions of acute phase having multiple irregular depressions without surrounding elevations. 2. The gastric antrum was involved alone or in part in all cases. Duodenal bulb was involved with gastric antrum in 4 cases. 3. The majority of the cases had multiple erosions. There were only 2 cases of single erosion. 4. In 65 cases of varioliform erosions; 1) The diameter of the surrounding elevations varied from 3 to 20 mm with the majority (47 cases) between 6 and 10 mm. 2) In general, the surrounding elevations with sharp margin on double contrast films were also clearly demonstrated on compression films but those with faint margin were not. 3) The size of the central barium collections varied from pinpoint to 10 mm with the majority under 5 mm. The shape of the central barium collections in majority of the cases were round with a few cases of linear, triangular or star-shape. 5. In 5 cases of acute phase erosions; 1) All the 5 cases were females. 2) On double contrast radiography, all the cases showed multiple irregular depressed lesions without surrounding elevations. 3) 1 case had the history of hematemesis. 4) In 1 case, there was marked radiological improvement on follow-up study of 2 months interval. 6. In 23 cases, there were coexistent diseases with gastric mucosal erosions. These were 13 cases of duodenal bulb ulcers,7 cases of benign gastric ulcers and 3 others

  5. Cryopreservation of Human Mucosal Leukocytes.

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    Sean M Hughes

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

  6. Diverticular Disease of the Colon: Neuromuscular Function Abnormalities.

    Science.gov (United States)

    Bassotti, Gabrio; Villanacci, Vincenzo; Bernardini, Nunzia; Dore, Maria P

    2016-10-01

    Colonic diverticular disease is a frequent finding in daily clinical practice. However, its pathophysiological mechanisms are largely unknown. This condition is likely the result of several concomitant factors occurring together to cause anatomic and functional abnormalities, leading as a result to the outpouching of the colonic mucosa. A pivotal role seems to be played by an abnormal colonic neuromuscular function, as shown repeatedly in these patients, and by an altered visceral perception. There is recent evidence that these abnormalities might be related to the derangement of the enteric innervation, to an abnormal distribution of mucosal neuropeptides, and to low-grade mucosal inflammation. The latter might be responsible for the development of visceral hypersensitivity, often causing abdominal pain in a subset of these patients.

  7. Review article: uncomplicated diverticular disease of the colon.

    Science.gov (United States)

    Petruzziello, L; Iacopini, F; Bulajic, M; Shah, S; Costamagna, G

    2006-05-15

    Diverticular disease of the colon is the fifth most important gastrointestinal disease in terms of direct and indirect health care costs in western countries. Uncomplicated diverticular disease is defined as the presence of diverticula in the absence of complications such as perforation, fistula, obstruction and/or bleeding. The distribution of diverticula along the colon varies worldwide being almost always left-sided and directly related to age in western countries and right-sided where diet is rich in fibre. The pathophysiology of diverticular disease is complex and relates to abnormal colonic motility, changes in the colonic wall, chronic mucosal low-grade inflammation, imbalance in colonic microflora and visceral hypersensitivity. Moreover, there can be genetic factors involved in the development of colonic diverticula. The use of non-absorbable antibiotics is the mainstay of therapy in patients with mild to moderate symptoms, and the effect of fibre-supplementation alone does not appear to be significantly different from placebo, although no definite data are available. More recently, alternative treatments have been reported. Mesalazine acts as a local mucosal immunomodulator and has been shown to improve symptoms and prevent recurrence of diverticulitis. In addition, probiotics have also been shown to be beneficial by re-establishing a normal gut microflora. In this study, the current literature on uncomplicated diverticular disease of the colon is reviewed.

  8. Streptococcus agalactiae Inhibits Candida albicans Hyphal Development and Diminishes Host Vaginal Mucosal TH17 Response

    OpenAIRE

    Xiao-Yu Yu; Fei Fu; Wen-Na Kong; Qian-Kun Xuan; Dong-Hua Wen; Xiao-Qing Chen; Yong-Ming He; Li-Hua He; Jian Guo; Ai-Ping Zhou; Yang-Hong Xi; Li-Jun Ni; Yu-Feng Yao; Wen-Juan Wu

    2018-01-01

    Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans, and that EFG1-Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC), the...

  9. Alpha-Toxin Promotes Mucosal Biofilm Formation by Staphylococcus aureus

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    Michele J Anderson

    2012-05-01

    Full Text Available Staphylococcus aureus causes numerous diseases in humans ranging from the mild skin infections to serious, life-threatening, superantigen-mediated Toxic Shock Syndrome (TSS. S. aureus may also be asymptomatically carried in the anterior nares, vagina or on the skin, which serve as reservoirs for infection. Pulsed-field gel electrophoresis clonal type USA200 is the most widely disseminated colonizer and a major cause of TSS. Our prior studies indicated that α-toxin was a major epithelial proinflammatory exotoxin produced by TSS S. aureus USA200 isolates. It also facilitated the penetration of TSS Toxin-1 (TSST-1 across vaginal mucosa. However, the majority of menstrual TSS isolates produce low α-toxin due to a nonsense point mutation at codon 113, designated hly, suggesting mucosal adaptation. The aim of this study was to characterize the differences between TSS USA200 strains [high (hla+ and low (hly+ α-toxin producers] in their abilities to infect and disrupt vaginal mucosal tissue. A mucosal model was developed using ex vivo porcine vaginal mucosa, LIVE/DEAD® staining and confocal microscropy to characterize biofilm formation and tissue viability of TSS USA 200 isolates CDC587 and MN8, which contain the α-toxin pseudogene (hly, MNPE (hla+ and MNPE isogenic hla knockout (hlaKO. All TSS strains grew to similar bacterial densities (1-5 x 108 CFU on the mucosa and were proinflammatory over 3 days. However, MNPE formed biofilms with significant reductions in the mucosal viability whereas neither CDC587, MN8 (hly+, or MNPE hlaKO, formed biofilms and were less cytotoxic. The addition of exogenous, purified α-toxin to MNPE hlaKO restored the biofilm phenotype. Our studies suggest α-toxin affects S. aureus phenotypic growth on vaginal mucosa, by promoting tissue disruption and biofilm formation; and α–toxin mutants (hly are not benign colonizers, but rather form a different type of infection, which we have termed high density pathogenic

  10. Voice disorders in mucosal leishmaniasis.

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    Ana Cristina Nunes Ruas

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

  11. Colonic production of nitric oxide gas in ulcerative colitis, collagenous colitis and uninflamed bowel

    DEFF Research Database (Denmark)

    Perner, Anders; Lassen, Inge Nordgaard; Matzen, Peter

    2002-01-01

    BACKGROUND: Nitric oxide (NO) produced in excess by the inflamed human colon is generally considered a pathway of mucosal damage. In an attempt to quantify colonic mucosal production of NO in various forms of colitis we performed 'steady-state' gas perfusion of whole colon in 11 patients...... by neutron activation analysis and the chemiluminescence technique, respectively. RESULTS: The use of argon as a marker of colonic NO output was justified by complete recovery (96%+/-2; mean +/- s(x); n = 5) of argon in gas collected from the rectum and a constant output of NO at varying perfusion rates (25...... higher (P gas perfusion of whole colon using chemiluminescence technique for measurement of NO is a reliable method...

  12. A metaproteomic approach to study human-microbial ecosystems at the mucosal luminal interface.

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    Xiaoxiao Li

    Full Text Available Aberrant interactions between the host and the intestinal bacteria are thought to contribute to the pathogenesis of many digestive diseases. However, studying the complex ecosystem at the human mucosal-luminal interface (MLI is challenging and requires an integrative systems biology approach. Therefore, we developed a novel method integrating lavage sampling of the human mucosal surface, high-throughput proteomics, and a unique suite of bioinformatic and statistical analyses. Shotgun proteomic analysis of secreted proteins recovered from the MLI confirmed the presence of both human and bacterial components. To profile the MLI metaproteome, we collected 205 mucosal lavage samples from 38 healthy subjects, and subjected them to high-throughput proteomics. The spectral data were subjected to a rigorous data processing pipeline to optimize suitability for quantitation and analysis, and then were evaluated using a set of biostatistical tools. Compared to the mucosal transcriptome, the MLI metaproteome was enriched for extracellular proteins involved in response to stimulus and immune system processes. Analysis of the metaproteome revealed significant individual-related as well as anatomic region-related (biogeographic features. Quantitative shotgun proteomics established the identity and confirmed the biogeographic association of 49 proteins (including 3 functional protein networks demarcating the proximal and distal colon. This robust and integrated proteomic approach is thus effective for identifying functional features of the human mucosal ecosystem, and a fresh understanding of the basic biology and disease processes at the MLI.

  13. ERK mediated upregulation of death receptor 5 overcomes the lack of p53 functionality in the diaminothiazole DAT1 induced apoptosis in colon cancer models: efficiency of DAT1 in Ras-Raf mutated cells.

    Science.gov (United States)

    Thamkachy, Reshma; Kumar, Rohith; Rajasekharan, K N; Sengupta, Suparna

    2016-03-08

    p53 is a tumour suppressor protein that plays a key role in many steps of apoptosis, and malfunctioning of this transcription factor leads to tumorigenesis. Prognosis of many tumours also depends upon the p53 status. Most of the clinically used anticancer compounds activate p53 dependent pathway of apoptosis and hence require p53 for their mechanism of action. Further, Ras/Raf/MEK/ERK axis is an important signaling pathway activated in many cancers. Dependence of diaminothiazoles, compounds that have gained importance recently due to their anticancer and anti angiogenic activities, were tested in cancer models with varying p53 or Ras/Raf mutational status. In this study we have used p53 mutated and knock out colon cancer cells and xenograft tumours to study the role of p53 in apoptosis mediated by diaminothiazoles. Colon cancer cell lines with varying mutational status for Ras or Raf were also used. We have also examined the toxicity and in vivo efficacy of a lead diaminothiazole 4-Amino-5-benzoyl-2-(4-methoxy phenylamino)thiazole (DAT1) in colon cancer xenografts. We have found that DAT1 is active in both in vitro and in vivo models with nonfunctional p53. Earlier studies have shown that extrinsic pathway plays major role in DAT1 mediated apoptosis. In this study, we have found that DAT1 is causing p53 independent upregulation of the death receptor 5 by activating the Ras/Raf/MEK/ERK signaling pathway both in wild type and p53 suppressed colon cancer cells. These findings are also confirmed by the in vivo results. Further, DAT1 is more efficient to induce apoptosis in colon cancer cells with mutated Ras or Raf. Minimal toxicity in both acute and subacute studies along with the in vitro and in vivo efficacy of DAT1 in cancers with both wild type and nonfunctional p53 place it as a highly beneficial candidate for cancer chemotherapy. Besides, efficiency in cancer cells with mutations in the Ras oncoprotein or its downstream kinase Raf raise interest in

  14. Mucosal healing in ulcerative colitis

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Coskun, Mehmet; Nielsen, Ole Haagen

    2013-01-01

    Ulcerative colitis (UC) is a colonic inflammatory condition with a substantial impact on the quality of life of affected persons. The disease carries a cumulative risk of need of colectomy of 20-30% and an estimated cumulative risk of colorectal cancer of 18% after 30 years of disease duration. W...

  15. Eosinophils in mucosal immune responses

    Science.gov (United States)

    Travers, J; Rothenberg, M E

    2015-01-01

    Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells. PMID:25807184

  16. Transcatheter emboilization therapy of massive colonic bleeding

    International Nuclear Information System (INIS)

    Shin, G. H.; Oh, J. H.; Yoon, Y.

    1996-01-01

    To evaulate the efficacy and safety of emergent superselective transcatheter embolization for controlling massive colonic bleeding. Six of the seven patients who had symptom of massive gastrointestinal bleeding underwent emergent transcatheter embolization for control of the bleeding. Gastrointestinal bleeding in these patients was originated from various colonic diseases: rectal cancer(n=1), proctitis(n=1), benign ulcer(n=1), mucosal injury by ventriculoperitoneal shunt(n=1), and unknown(n=2). All patients except one with rectal cancer were critically ill. Superselective embolization were done by using Gelfoam particles and/or coils. The vessels embolized were ileocolic artery(n=1). superior rectal artery(n=2), inferior rectal artery (n=1), and middle and inferior rectal arteries(n=1). Hemostasis was successful immediately in all patients. Two underwnet surgery due to recurrent bleeding developed 3 days after the procedure(n=1) or in associalion with underlying rectal cancer(n=1). On surgical specimen of two cases, there was no mucosal ischemic change. Transcatheter embolization is a safe and effective treatment of method for the control of massive colonic bleeding

  17. Potassium transport across guinea pig distal colon

    International Nuclear Information System (INIS)

    Rechkemmer, G.; Halm, D.R.; Frizzell, R.A.

    1986-01-01

    Active absorption and secretion of K was studied by measuring bidirectional 42 K fluxes across short-circuited guinea pig distal colon. Tissues were pretreated with mucosal (m) and serosal (s) indomethacin (1 μM) and amiloride (0.1 mM, m) to suppress spontaneous, electrogenic Cl secretion and Na absorption. Under these conditions, the short-circuit current (I/sub sc/) was 0.4 μeq/cm 2 h while electroneutral K absorption was 2.8 μeq/cm 2 h. Epinephrine (5 μM, s) stimulated electrogenic K secretion, reducing net K absorption to 1.3 μeq/cm 2 h. Bumetanide (0.1 mM, s) abolished this K secretion and restored K absorption to control values, suggesting mechanistic similarities between K and Cl secretion. K absorption was inhibited 40% by the gastric H/K ATPase inhibitor, omeprazole (0.1 mM, m), and was abolished by ouabain (0.1 mM, m). Neutral K absorption does not appear to be mediated by an apical membrane Na/K pump since: the effect of mucosal ouabain on K absorption does not require the presence of mucosal or serosal Na, unidirectional Na fluxes are not influenced by mucosal ouabain, and K absorption is not affected when Na absorption is abolished by amiloride. Net K transport is determined by the balance between electroneutral K absorption and electrogenic K secretion. The ouabain sensitivity of K absorption suggests that colonic H/K ATPase differs from its gastric counterpart

  18. Rectal dexmedetomidine in rats: evaluation of sedative and mucosal effects

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    Volkan Hanci

    2015-02-01

    Full Text Available BACKGROUND AND OBJECTIVES: In this study, we investigated the anesthetic and mucosal effects of the rectal application of dexmedetomidine to rats. METHODS: Male Wistar albino rats weighing 250-300 g were divided into four groups: Group S (n = 8 was a sham group that served as a baseline for the normal basal values; Group C (n = 8 consisted of rats that received the rectal application of saline alone; Group IPDex (n = 8 included rats that received the intraperitoneal application of dexmedetomidine (100 µg kg-1; and Group RecDex (n = 8 included rats that received the rectal application of dexmedetomidine (100 µg kg-1. For the rectal drug administration, we used 22 G intravenous cannulas with the stylets removed. We administered the drugs by advancing the cannula 1 cm into the rectum, and the rectal administration volume was 1 mL for all the rats. The latency and anesthesia time (min were measured. Two hours after rectal administration, 75 mg kg-1 ketamine was administered for intraperitoneal anesthesia in all the groups, followed by the removal of the rats' rectums to a distal distance of 3 cm via an abdominoperineal surgical procedure. We histopathologically examined and scored the rectums. RESULTS: Anesthesia was achieved in all the rats in the Group RecDex following the administration of dexmedetomidine. The onset of anesthesia in the Group RecDex was significantly later and of a shorter duration than in the Group IPDEx (p < 0.05. In the Group RecDex, the administration of dexmedetomidine induced mild-moderate losses of mucosal architecture in the colon and rectum, 2 h after rectal inoculation. CONCLUSION: Although 100 µg kg-1 dexmedetomidine administered rectally to rats achieved a significantly longer duration of anesthesia compared with the rectal administration of saline, our histopathological evaluations showed that the rectal administration of 100 µg kg-1 dexmedetomidine led to mild-moderate damage to the mucosal structure of the

  19. BISPHOSPHONATE - RELATED MUCOSITIS (BRM: A CASE REPORT

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    Pavel Stanimirov

    2017-03-01

    Full Text Available Bisphosphonates (BPs are the most widely used and effective antiresorptive agents for the treatment of diseases in which there is an increase in osteoclastic resorption, including post-menopausal osteoporosis, Paget’s disease, and tumor-associated osteolysis. Oral and maxillofacial surgeons are well aware of the side effects of bisphosphonates and mainly with bisphosphonate-related osteonecrosis of the jaws (BRONJ. Less known are the mucosal lesions associated with the use of these agents. In the scientific literature, there are only few reports of mucosal lesions due to the direct contact of the oral form of BPs with the mucosa (bisphosphonate-related mucositis. They are mostly related to improper use of bisphosphonate tablets that are chewed, sucked or allowed to melt in the mouth before swallowing. Lesions are atypical and need to be differentiated from other mucosal erosions. We present a case of bisphosphonate-related mucositis due to the improper use of alendronate.

  20. Development of oral mucositis model induced by radiation in hamsters: prevention and treatment with low power laser

    Energy Technology Data Exchange (ETDEWEB)

    Galletta, Vivian C.; Folgosi-Correa, Melissa S.; Zezell, Denise M., E-mail: vivian.galletta@gmail.com, E-mail: melfolgosi@gmail.com, E-mail: zezell@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Gouw-Soares, Sheila, E-mail: sheilagouw@hotmail.com [Universidade Cruzeiro do Sul (UNICSUL), Sao Paulo, SP (Brazil). Fac. de Odontologia; Correa, Luciana, E-mail: lcorrea@usp.br [Universidade de Sao Paulo (FO/USP), SP (Brazil). Fac. de Odontologia

    2013-07-01

    Despite the benefits for the prognosis of patients treated with radiotherapy for oral cancer treatment, it might cause local side effects such as oral mucositis. The oral mucositis is a pathological condition that may appear in affected oral mucosa by ionizing radiation, and the pain related can alter and even stop the antineoplastic treatment, decreasing tumor control rates. Oral mucositis has several treatment modalities, although it remains as a problem since therapies available are not enough to treat efficiently this inflammatory process. Many pharmacological solutions (anti-inflammatory, antibiotics, antiseptic, lubricant agents) are used to alleviate oral mucositis symptoms. Laser treatment has been used as an option, but there is lack of studies to verify the process of laser therapy in oral mucositis caused by ionizing radiation. This work accomplishes follow-up of oral mucositis evolution, comparing laser and benzydamine therapies in an animal model. Forty-two animals were irradiated at head and neck in a single dose of 30 Grays, by means of a Co{sup 60} source. After irradiation, treatments were applied daily, once a day, for 20 days, in which severity of lesions were clinically classified by two calibrated examiners. Histological evaluation was performed to search for mucosal alterations at treated tissues. Statistical analysis of data showed that laser treatment was more efficient than benzydamine treatment, diminishing severity and duration of oral mucosal lesions caused by ionizing irradiation. (author)

  1. Development of oral mucositis model induced by radiation in hamsters: prevention and treatment with low power laser

    International Nuclear Information System (INIS)

    Galletta, Vivian C.; Folgosi-Correa, Melissa S.; Zezell, Denise M.; Gouw-Soares, Sheila; Correa, Luciana

    2013-01-01

    Despite the benefits for the prognosis of patients treated with radiotherapy for oral cancer treatment, it might cause local side effects such as oral mucositis. The oral mucositis is a pathological condition that may appear in affected oral mucosa by ionizing radiation, and the pain related can alter and even stop the antineoplastic treatment, decreasing tumor control rates. Oral mucositis has several treatment modalities, although it remains as a problem since therapies available are not enough to treat efficiently this inflammatory process. Many pharmacological solutions (anti-inflammatory, antibiotics, antiseptic, lubricant agents) are used to alleviate oral mucositis symptoms. Laser treatment has been used as an option, but there is lack of studies to verify the process of laser therapy in oral mucositis caused by ionizing radiation. This work accomplishes follow-up of oral mucositis evolution, comparing laser and benzydamine therapies in an animal model. Forty-two animals were irradiated at head and neck in a single dose of 30 Grays, by means of a Co 60 source. After irradiation, treatments were applied daily, once a day, for 20 days, in which severity of lesions were clinically classified by two calibrated examiners. Histological evaluation was performed to search for mucosal alterations at treated tissues. Statistical analysis of data showed that laser treatment was more efficient than benzydamine treatment, diminishing severity and duration of oral mucosal lesions caused by ionizing irradiation. (author)

  2. Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

    Directory of Open Access Journals (Sweden)

    Logan Richard M

    2010-03-01

    Full Text Available Abstract Background Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.

  3. Model systems to analyze the role of miRNAs and commensal microflora in bovine mucosal immune system development.

    Science.gov (United States)

    Liang, Guanxiang; Malmuthuge, Nilusha; Guan, Le Luo; Griebel, Philip

    2015-07-01

    Information is rapidly accumulating regarding the role of miRNAs as key regulators of immune system development and function. It is also increasingly evident that miRNAs play an important role in host-pathogen interactions through regulation of both innate and acquired immune responses. Little is known, however, about the specific role of miRNAs in regulating normal development of the mucosal immune system, especially during the neonatal period. Furthermore, there is limited knowledge regarding the possible role the commensal microbiome may play in regulating mucosal miRNAs expression, although evidence is emerging that a variety of enteric pathogens influence miRNA expression. The current review focuses on recent information that miRNAs play an important role in regulating early development of the bovine mucosal immune system. A possible role for the commensal microbiome in regulating mucosal development by altering miRNA expression is also discussed. Finally, we explore the potential advantages of using the newborn calf as a model to determine how interactions between developmental programming, maternal factors in colostrum, and colonization of the gastrointestinal tract by commensal bacteria may alter mucosal miRNA expression and immune development. Identifying the key factors that regulate mucosal miRNA expression is critical for understanding how the balance between protective immunity and inflammation is maintained to ensure optimal gastrointestinal tract function and health of the whole organism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Absence of mucosal inflammation in uncomplicated diverticular disease.

    Science.gov (United States)

    Elli, Luca; Roncoroni, Leda; Bardella, Maria Teresa; Terrani, Claudia; Bonura, Antonella; Ciulla, Michele; Marconi, Stefano; Piodi, Luca

    2011-07-01

    Uncomplicated diverticular disease is a common condition in patients older than 50 years. Symptoms are aspecific and overlapping with those of irritable bowel syndrome. Nowadays, patients are often treated with antinflammatory drugs (5-aminosalicilic acid). Our purpose was to evaluate the presence of inflammation in the colonic mucosa of patients with symptomatic uncomplicated diverticular disease compared with subjects without diverticula. Endoscopic biopsies of colon from 10 patients with symptomatic uncomplicated diverticular disease and 10 from subjects without diverticula (controls) were taken. Specimens were homogenised and IL2, IL4, IL5, IL8, IL10, IL12p70, IL13, IFN gamma, TNF alfa (searchlight multiplex technique), TGF beta, transglutaminase type 2 and caspase 9 were measured. Histochemistry for transglutaminase type 2 and TUNEL were performed on the histological sections, in addition to morphologic evaluation, as markers of tissue remodelling and apoptosis. For statistical analysis Student's t test and Spearman correlation test were used. No histological differences were detected between the patients with an uncomplicated diverticular disease and controls. Mean values of mucosal cytokines and of the other tested parameters did not show statistically significant differences between patients with uncomplicated diverticular disease and controls. Even if based on a small number of patients, the study demonstrates the absence of inflammation in the mucosa of subjects affected by uncomplicated diverticular disease.

  5. Streptococcus agalactiae Inhibits Candida albicans Hyphal Development and Diminishes Host Vaginal Mucosal TH17 Response

    Directory of Open Access Journals (Sweden)

    Xiao-Yu Yu

    2018-02-01

    Full Text Available Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans, and that EFG1-Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC, the fungal burden and the levels of pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α showed a increase on co-infection with S. agalactiae, while the level of TH17 T cells and IL-17 in the cervicovaginal lavage fluid were significantly decreased. Our results indicate that S. agalactiae inhibits C. albicans hyphal development by downregulating the expression of EFG1-Hwp1. The interaction between S. agalactiae and C. albicans may attenuate host vaginal mucosal TH17 immunity and contribute to mucosal colonization by C. albicans.

  6. Streptococcus agalactiae Inhibits Candida albicans Hyphal Development and Diminishes Host Vaginal Mucosal TH17 Response.

    Science.gov (United States)

    Yu, Xiao-Yu; Fu, Fei; Kong, Wen-Na; Xuan, Qian-Kun; Wen, Dong-Hua; Chen, Xiao-Qing; He, Yong-Ming; He, Li-Hua; Guo, Jian; Zhou, Ai-Ping; Xi, Yang-Hong; Ni, Li-Jun; Yao, Yu-Feng; Wu, Wen-Juan

    2018-01-01

    Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans , and that EFG1 -Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC), the fungal burden and the levels of pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α showed a increase on co-infection with S. agalactiae , while the level of TH17 T cells and IL-17 in the cervicovaginal lavage fluid were significantly decreased. Our results indicate that S. agalactiae inhibits C. albicans hyphal development by downregulating the expression of EFG1 -Hwp1. The interaction between S. agalactiae and C. albicans may attenuate host vaginal mucosal TH17 immunity and contribute to mucosal colonization by C. albicans .

  7. A regenerative approach towards mucosal fenestration closure

    Science.gov (United States)

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

    2013-01-01

    Mucosal fenestration is an opening or an interstice through the oral mucosa. A lesion which occurs with greater frequency than generally realised, its occurrence is attributed to a myriad of causes. Mucogingival procedures including connective tissue grafts, free gingival grafts and lateral pedicle grafts are generally considered to be the treatment of choice in the closure of a mucosal fenestration. More often, these procedures are performed in conjunction with other procedures such as periradicular surgery and with bone grafts. However, the concomitant use of gingival grafts and bone grafts in mucosal fenestrations secondary to infections in sites exhibiting severe bone loss is highly debatable. In this article, we report two cases of mucosal fenestrations secondary to trauma and their management by regenerative periodontal surgery with the placement of guided tissue regeneration membrane and bone graft. The final outcome was a complete closure of the fenestration in both the cases. PMID:23749826

  8. Transgenic Killer Commensal Bacteria as Mucosal Protectants

    Directory of Open Access Journals (Sweden)

    Luciano Polonelli

    2001-01-01

    Full Text Available As first line of defense against the majority of infections and primary site for their transmission, mucosal surfaces of the oral cavity and genitourinary, gastrointestinal, and respiratory tracts represent the most suitable sites to deliver protective agents for the prevention of infectious diseases. Mucosal protection is important not only for life threatening diseases but also for opportunistic infections which currently represent a serious burden in terms of morbidity, mortality, and cost of cures. Candida albicans is among the most prevalent causes of mucosal infections not only in immuno- compromised patients, such as HIV-infected subjects who are frequently affected by oral and esophageal candidiasis, but also in otherwise healthy individuals, as in the case of acute vaginitis. Unfortunately, current strategies for mucosal protection against candidiasis are severely limited by the lack of effective vaccines and the relative paucity and toxicity of commercially available antifungal drugs. An additional option has been reported in a recent

  9. Microneedle and mucosal delivery of influenza vaccines

    Science.gov (United States)

    Kang, Sang-Moo; Song, Jae-Min; Kim, Yeu-Chun

    2017-01-01

    In recent years with the threat of pandemic influenza and other public health needs, alternative vaccination methods other than intramuscular immunization have received great attention. The skin and mucosal surfaces are attractive sites probably because of both non-invasive access to the vaccine delivery and unique immunological responses. Intradermal vaccines using a microinjection system (BD Soluvia) and intranasal vaccines (FluMist) are licensed. As a new vaccination method, solid microneedles have been developed using a simple device that may be suitable for self-administration. Because coated micorneedle influenza vaccines are administered in the solid state, developing formulations maintaining the stability of influenza vaccines is an important issue to be considered. Marketable microneedle devices and clinical trials remain to be developed. Other alternative mucosal routes such as oral and intranasal delivery systems are also attractive for inducing cross protective mucosal immunity but effective non-live mucosal vaccines remain to be developed. PMID:22697052

  10. Use of 60Co panoramic source in the induction of oral mucositis in rats

    International Nuclear Information System (INIS)

    Andrade, Maira F.; Benetti, Carolina; Zezell, Denise M.; Correa, Luciana

    2013-01-01

    Oral Mucositis is a well-known side effect of chemo-radiotherapy in cancer patients or transplant recipients that could induce hospitalization or impairs therapy in different levels of severity. This study is devoted to define the first steps in the research of low level laser treatments in oral mucositis, proposing a 60 Co radiation to experimentally induce oral mucositis in rats using Panoramic gamma irradiator, simulating usual radiotherapy of head and neck cancer. Fifteen male Wistar rats, above 250g, were irradiated at Centro de Tecnologia das Radiacoes (IPEN - CNEN/SP) and divided in three experimental groups, with different single doses of radiation (30 Gy, 25 Gy and 20 Gy). The animals were observed for a 20 days period. Animals that received 30 Gy and 25 Gy developed greater severity of mucositis and premature euthanasia was performed in these groups on the 7th and 11th day after the irradiation, respectively. The 20 Gy group developed oral mucositis grading from moderated to severe between the days 7 and 11 after irradiation, with progressive body mass loss and decrease in the intake of food and water. These animals recovered from oral mucositis around the 18th day and clinical remission at the 20th day. The single dose of 20 Gy Gamma radiation proved to be efficient way for inducing oral mucositis in rats, allowing the establishment of an experimental model for oral mucositis in rats for future use on interventions of this serious aspect of radiation therapy, such as laser therapy using different wave lengths and power densities. (author)

  11. Use of {sup 60}Co panoramic source in the induction of oral mucositis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Maira F.; Benetti, Carolina; Zezell, Denise M., E-mail: mairandrade@yahoo.com, E-mail: zezell@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Correa, Luciana, E-mail: lcorrea@usp.br [Universidade de Sao Paulo (FO/USP), Sao Paulo, SP (Brazil). Fac. de Odontologia

    2013-07-01

    Oral Mucositis is a well-known side effect of chemo-radiotherapy in cancer patients or transplant recipients that could induce hospitalization or impairs therapy in different levels of severity. This study is devoted to define the first steps in the research of low level laser treatments in oral mucositis, proposing a {sup 60}Co radiation to experimentally induce oral mucositis in rats using Panoramic gamma irradiator, simulating usual radiotherapy of head and neck cancer. Fifteen male Wistar rats, above 250g, were irradiated at Centro de Tecnologia das Radiacoes (IPEN - CNEN/SP) and divided in three experimental groups, with different single doses of radiation (30 Gy, 25 Gy and 20 Gy). The animals were observed for a 20 days period. Animals that received 30 Gy and 25 Gy developed greater severity of mucositis and premature euthanasia was performed in these groups on the 7th and 11th day after the irradiation, respectively. The 20 Gy group developed oral mucositis grading from moderated to severe between the days 7 and 11 after irradiation, with progressive body mass loss and decrease in the intake of food and water. These animals recovered from oral mucositis around the 18th day and clinical remission at the 20th day. The single dose of 20 Gy Gamma radiation proved to be efficient way for inducing oral mucositis in rats, allowing the establishment of an experimental model for oral mucositis in rats for future use on interventions of this serious aspect of radiation therapy, such as laser therapy using different wave lengths and power densities. (author)

  12. Pathogenic bacteria colonizing the airways in asymptomatic neonates stimulates topical inflammatory mediator release

    DEFF Research Database (Denmark)

    Følsgaard, Nilofar Vahman; Schjørring, Susanne; Chawes, Bo Lund Krogsgaard

    2013-01-01

    Rationale: Bacterial colonization of neonatal airways with the pathogenic bacterial species, Moraxella catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae, is associated with later development of childhood asthma. Objectives: To study a possible association between colonization...... with pathogenic bacterial strains and the immune signature of the upper airways in healthy neonates. Methods: A total of 20 cytokines and chemokines were quantified in vivo in the airway mucosal lining fluid of 662 neonates from the Copenhagen Prospective Study of Asthma in Childhood 2010 birth cohort...

  13. Diverticular colitis of the ascending colon preceding the onset of ulcerative colitis

    OpenAIRE

    Maeshiro, Tatsuji; Hokama, Akira; Kinjo, Tetsu; Fujita, Jiro

    2014-01-01

    We present a case of diverticular colitis of the ascending colon preceding the onset of ulcerative colitis. A 58-year-old man presented with positive faecal occult blood test. Colonoscopy disclosed diverticular colitis of the ascending colon. After a year's follow-up, typical ulcerative colitis developed and diverticular colitis improved. Diverticular colitis is a newly established disorder of chronic segmental mucosal inflammation affected by diverticular disease. There is increasing recogni...

  14. Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon.

    OpenAIRE

    Alzamora, Rodrigo; O'Mahony, Fiona; Harvey, Brian J

    2011-01-01

    Excessive Cl(-) secretion is the driving force for secretory diarrhea. 17β-Estradiol has been shown to inhibit Cl(-) secretion in rat distal colon through a nongenomic pathway. We examined whether 17β-estradiol inhibits Cl(-) secretion in an animal model of secretory diarrhea and the downstream effectors involved. The effect of 17β-estradiol on cholera toxin and heat-stable enterotoxin induced Cl(-) secretion in rat colonic mucosal sheets was studied by current-voltage clamping. Selective per...

  15. Clotrimazole nanoparticle gel for mucosal administration

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Elisabetta, E-mail: ese@unife.it [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Ravani, Laura [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Contado, Catia [Department of Chemistry, University of Ferrara, Ferrara (Italy); Costenaro, Andrea [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Drechsler, Markus [Macromolecular Chemistry II, University of Bayreuth (Germany); Rossi, Damiano [Department of Biology and Evolution, LT Terra and Acqua Tech UR7, University of Ferrara, Ferrara (Italy); Menegatti, Enea [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Grandini, Alessandro [Department of Biology and Evolution, LT Terra and Acqua Tech UR7, University of Ferrara, Ferrara (Italy); Cortesi, Rita [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy)

    2013-01-01

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

  16. Clotrimazole nanoparticle gel for mucosal administration

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  17. Colonic lymphoid follicles associated with colonic neoplasms

    International Nuclear Information System (INIS)

    Glick, S.N.; Teplick, S.K.; Ross, W.M.

    1986-01-01

    The authors prospectively evaluated 62 patients over 40 years old in whom lymphoid follicles were demonstrated on double-contrast enema examinations. Eighteen patients (29%) had no current radiographic evidence of, or history of, colonic neoplasms. Forty-four patients (71%) had an associated neoplasm. Fourteen patients had associated colonic carcinoma, and ten patients had a history of a previously resected colon cancer. One patient had previously undergone resection for ''polyps.'' Twenty-two patients had an associated ''polyp.'' There were no clinical or radiographic features that could reliably distinguish the neoplastic from the nonneoplastic groups. However, lymphoid follicles in the left colon or diffusely involving the colon were more likely to be associated with a colonic neoplasm. Lymphoid follicles were almost always identified near a malignant lesion

  18. Endoscopic mucosal resection of flat and sessile colorectal adenomas: Our experience with long-term follow-ups

    Directory of Open Access Journals (Sweden)

    Grgov Saša

    2014-01-01

    Full Text Available Bacground/Aim. Endoscopic mucosal resection (EMR or mucosectomy is a removing method of flat or sessile lesions, laterally spreading tumors and carcinoma of the colon or the rectum limited to mucosa or the surface part of the submucosa. The aim of the study was to estimate the efficacy and safety of EMR in removing flat and sessile colorectal adenomas. Methods. This prospective study involved 140 patients during the period of 8 years. A total of 187 colorectal adenomas were removed using the EMR method “inject and cut with snare”. Results. The approximate size of mucosectomised adenomas was 13.6 mm (from 8 mm to 60 mm. There was a total of 48 (25.7% flat adenomas and 139 (74.3% sessile adenomas, (p < 0.01. Using “en bloc” and “piecemeal” resection, 173 (92.5% and 14 (7.5% of colorectal adenomas were removed, respectively. In all the cases, a complete removal of colorectal adenomas was achieved. Two (1.4% patients had adenoma removal with intramucosal carcinoma each. In the average follow-up period of 21.2 ± 17.8 months, 2 (1.4% patients had adenoma relapse after EMR. Considering complications, there was bleeding in 1 (0.7% patient with a big rectum adenoma removed with EMR. Furthermore, one (0.7% patient had a postcoagulation syndrome after cecal adenoma was removed by EMR. Conclusion. EMR is an efficient, safe and minimally invasive technique of removing flat and sessile adenomas in the colon and the rectum, with a very low percentage of adenoma recurrence over a long period of monitoring.

  19. Mucosal immunogenicity of plant lectins in mice

    Science.gov (United States)

    Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O’Hagan, D T

    2000-01-01

    The mucosal immunogenicity of a number of plant lectins with different sugar specificities was investigated in mice. Following intranasal (i.n.) or oral administration, the systemic and mucosal antibody responses elicited were compared with those induced by a potent mucosal immunogen (cholera toxin; CT) and a poorly immunogenic protein (ovalbumin; OVA). After three oral or i.n. doses of CT, high levels of specific serum antibodies were measured and specific IgA was detected in the serum, saliva, vaginal wash, nasal wash and gut wash of mice. Immunization with OVA elicited low titres of serum IgG but specific IgA was not detected in mucosal secretions. Both oral and i.n. delivery of all five plant lectins investigated [Viscum album (mistletoe lectin 1; ML‐1), Lycospersicum esculentum (tomato lectin; LEA), Phaseolus vulgaris (PHA), Triticum vulgaris (wheat germ agglutinin (WGA), Ulex europaeus I (UEA‐1)] stimulated the production of specific serum IgG and IgA antibody after three i.n. or oral doses. Immunization with ML‐1 induced high titres of serum IgG and IgA in addition to specific IgA in mucosal secretions. The response to orally delivered ML‐1 was comparable to that induced by CT, although a 10‐fold higher dose was administered. Immunization with LEA also induced high titres of serum IgG, particularly after i.n. delivery. Low specific IgA titres were also detected to LEA in mucosal secretions. Responses to PHA, WGA and UEA‐1 were measured at a relatively low level in the serum, and little or no specific mucosal IgA was detected. PMID:10651938

  20. Assessing the colonic microbiome, hydrogenogenic and hydrogenotrophic genes, transit and breath methane in constipation.

    Science.gov (United States)

    Wolf, P G; Parthasarathy, G; Chen, J; O'Connor, H M; Chia, N; Bharucha, A E; Gaskins, H R

    2017-10-01

    Differences in the gut microbiota and breath methane production have been observed in chronic constipation, but the relationship between colonic microbiota, transit, and breath tests remains unclear. In 25 healthy and 25 constipated females we evaluated the sigmoid colonic mucosal and fecal microbiota using 16S rRNA gene sequencing, abundance of hydrogenogenic FeFe (FeFe-hydA) and hydrogenotrophic (methyl coenzyme M reductase A [mrcA] and dissimilatory sulfite reductase A [dsrA]) genes with real-time qPCR assays, breath hydrogen and methane levels after oral lactulose, and colonic transit with scintigraphy. Breath hydrogen and methane were not correlated with constipation, slow colon transit, or with abundance of corresponding genes. After adjusting for colonic transit, the abundance of FeFehydA, dsrA, and mcrA were greater (Ptransit, and overall microbiome composition. In the colonic mucosa and feces, the abundance of hydrogenogenic and hydrogenotrophic genes were positively correlated (Ptransit. Corroborating our earlier findings with 16S rRNA genes, colonic mucosal but not fecal hydrogenogenic and hydrogenotrophic genes were more abundant in constipated vs. healthy subjects independent of colonic transit. Breath gases do not directly reflect the abundance of target genes contributing to their production. © 2017 John Wiley & Sons Ltd.

  1. Antegrade Colonic Lavage in Acute Colonic Obstruction

    OpenAIRE

    Foster, Michael E.; Johnson, Colin D.

    1986-01-01

    Conventional management of acute left sided colonic obstruction employs some form of proximal colostomy. Intraoperative antegrade colonic irrigation relieves proximal faecal loading and may permit safer primary resection and anastomosis. The results of a pilot study are presented, and are shown to be favourable.

  2. A novel role for the NLRC4 inflammasome in mucosal defenses against the fungal pathogen Candida albicans.

    Directory of Open Access Journals (Sweden)

    Jeffrey Tomalka

    2011-12-01

    Full Text Available Candida sp. are opportunistic fungal pathogens that colonize the skin and oral cavity and, when overgrown under permissive conditions, cause inflammation and disease. Previously, we identified a central role for the NLRP3 inflammasome in regulating IL-1β production and resistance to dissemination from oral infection with Candida albicans. Here we show that mucosal expression of NLRP3 and NLRC4 is induced by Candida infection, and up-regulation of these molecules is impaired in NLRP3 and NLRC4 deficient mice. Additionally, we reveal a role for the NLRC4 inflammasome in anti-fungal defenses. NLRC4 is important for control of mucosal Candida infection and impacts inflammatory cell recruitment to infected tissues, as well as protects against systemic dissemination of infection. Deficiency in either NLRC4 or NLRP3 results in severely attenuated pro-inflammatory and antimicrobial peptide responses in the oral cavity. Using bone marrow chimeric mouse models, we show that, in contrast to NLRP3 which limits the severity of infection when present in either the hematopoietic or stromal compartments, NLRC4 plays an important role in limiting mucosal candidiasis when functioning at the level of the mucosal stroma. Collectively, these studies reveal the tissue specific roles of the NLRP3 and NLRC4 inflammasome in innate immune responses against mucosal Candida infection.

  3. The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention

    Science.gov (United States)

    McFadden, Rita-Marie T.; Larmonier, Claire B.; Shehab, Kareem W.; Midura-Kiela, Monica; Ramalingam, Rajalakshmy; Harrison, Christy A.; Besselsen, David G.; Chase, John H.; Caporaso, J. Gregory; Jobin, Christian; Ghishan, Fayez K.; Kiela, Pawel R.

    2015-01-01

    Background Intestinal microbiota influences the progression of colitis-associated colorectal cancer (CAC). With diet being a key determinant of the gut microbial ecology, dietary interventions are an attractive avenue for the prevention of CAC. Curcumin is the most active constituent of the ground rhizome of the Curcuma Longa plant, which has been demonstrated to have anti-inflammatory, anti-oxidative and anti-proliferative properties. Methods Il10−/− mice on 129/SvEv background were used as a model of CAC. Starting at 10 weeks of age, WT or Il10−/− mice received six weekly i.p. injections of azoxymethane (AOM) or saline, and were started on either a control or curcumin-supplemented diet. Stools were collected every 4 weeks for microbial community analysis. Mice were sacrificed at 30 weeks of age. Results Curcumin-supplemented diet increased survival, decreased colon weight/length ratio, and at 0.5%, entirely eliminated tumor burden. Although colonic histology indicated improvement with curcumin, no effects of mucosal immune responses have been observed in PBS/Il10−/− mice, and limited effects were seen in AOM/Il10−/− mice. In WT and in Il10−/− mice, curcumin increased bacterial richness, prevented age-related decrease in alpha diversity, increased the relative abundance of Lactobacillales, and decreased Coriobacterales order. Taxonomic profile of AOM/Il10−/− mice receiving curcumin was more similar to those of wild-type mice than those fed control diet. Conclusions In AOM/Il10−/− model, curcumin reduced or eliminated colonic tumor burden with limited effects on mucosal immune responses. The beneficial effect of curcumin on tumorigenesis was associated with the maintenance of a more diverse colonic microbial ecology. PMID:26218141

  4. Mucositis and oral infections secondary to gram negative rods in patients with prolonged neutropenia

    Directory of Open Access Journals (Sweden)

    Mindy M. Sampson

    2017-01-01

    Full Text Available Patients with prolonged neutropenia are at risk for a variety of complications and infections including the development of mucositis and oral ulcers. The changes in oral flora during chemotherapy and its effects on the development of infections of the oral cavity have been studied with inconsistent results. However, there is evidence that supports the colonization of gram negative rods in patients undergoing chemotherapy. In this report, we present two leukemic patients who developed oral ulcers secondary to multi-drug resistant Pseudomonas aeruginosa. It is important to suspect multi-drug resistant gram negative rods in patients with prolonged neutropenia who develop gum infections despite appropriate antibiotic coverage.

  5. Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    2014-10-01

    Full Text Available Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer, a synthetic glycolipid agonist of natural killer T (NKT cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.

  6. Management of Colonic Volvulus

    Science.gov (United States)

    Gingold, Daniel; Murrell, Zuri

    2012-01-01

    Colonic volvulus is a common cause of large bowel obstruction worldwide. It can affect all parts of the colon, but most commonly occurs in the sigmoid and cecal areas. This disease has been described for centuries, and was studied by Hippocrates himself. Currently, colonic volvulus is the third most common cause of large bowel obstruction worldwide, and is responsible for ∼15% of large bowel obstructions in the United States. This article will discuss the history of colonic volvulus, and the predisposing factors that lead to this disease. Moreover, the epidemiology and diagnosis of each type of colonic volvulus, along with the various treatment options will be reviewed. PMID:24294126

  7. Gastric and colonic mantle cell lymphoma - incidental discovery.

    Science.gov (United States)

    Pitigoi, Dan; Stoica, Victor; Stoia, Razvan; Dobrea, Camelia; Becheanu, Gabriel; Diculescu, Mircea

    2009-03-01

    A 65-year old patient, with no medical history, was admitted for lower gastrointestinal bleeding. On clinical examination the patient seemed to be in good health. However the examination was completed with a rectosigmoidoscopy revealing the presence of mucosal erosions, ulcerations, multiple papulae. The histopathological examination raised the suspicion of a colonic lymphoma. Gastric biopsies suggested a gastric MALT type lymphoma associated to the colonic lymphoma, but the immunohistochemical profile corresponded to a mantle cell lymphoma. In spite of the general poor prognosis of mantle cell lymphoma, our patient had a good clinical and endoscopic response to the standard cyclophosphamide, vincristine, prednisone (CVP) therapy. The cases of gastric and colonic mantle lymphoma are rare, the response to therapy is poor; fortunately, our patient had a complete resolution after completion of the six cycles of chemotherapy.

  8. Role of Lactobacilli and Lactoferrin in the Mucosal Cervicovaginal Defense

    Directory of Open Access Journals (Sweden)

    Piera Valenti

    2018-03-01

    Full Text Available The innate defense system of the female mucosal genital tract involves a close and complex interaction among the healthy vaginal microbiota, different cells, and various proteins that protect the host from pathogens. Vaginal lactobacilli and lactoferrin represent two essential actors in the vaginal environment. Lactobacilli represent the dominant bacterial species able to prevent facultative and obligate anaerobes outnumber in vaginal microbiota maintaining healthy microbial homeostasis. Several mechanisms underlie the protection exerted by lactobacilli: competition for nutrients and tissue adherence, reduction of the vaginal pH, modulation of immunity, and production of bioactive compounds. Among bioactive factors of cervicovaginal mucosa, lactoferrin, an iron-binding cationic glycoprotein, is a multifunctional glycoprotein with antibacterial, antifungal, antiviral, and antiparasitic activities, recently emerging as an important modulator of inflammation. Lactobacilli and lactoferrin are largely under the influence of female hormones and of paracrine production of various cytokines. Lactoferrin is strongly increased in lower genital tract mucosal fluid of women affected by Neisseria gonorrheae, Chlamydia trachomatis, and Trichomonas vaginalis infections promoting both innate and adaptive immune responses. In vaginal dysbiosis characterized by low amounts of vaginal lactobacilli and increased levels of endogenous anaerobic bacteria, the increase in lactoferrin could act as an immune modulator assuming the role normally played by the healthy microbiota in vaginal mucosa. Then lactoferrin and lactobacilli may be considered as biomarkers of altered microbial homeostasis at vaginal level. Considering the shortage of effective treatments to counteract recurrent and/or antibiotic-resistant bacterial infections, the intravaginal administration of lactobacilli and lactoferrin could be a novel efficient therapeutic strategy and a valuable tool to restore

  9. PHENOTYPIC FEATURES OF ENDOMETRIAL CANCER AND MSI IN COLON AND BLOOD SERUM

    Directory of Open Access Journals (Sweden)

    S. M. Kartashov

    2014-04-01

    Full Text Available Since the end of the last century an upward trend regarding hormone-dependent tumours of the reproductive system, including endometrial cancer (EC has been observed, with one of the trend reasons being increased number of mutations, in particular, microsatellite instability (MSI – the consequence of unpaired nucleotides repair system gene inactivation (MSH2, MSH3, MSH6, MLH1,PMS2, EXO1. This molecular genetic phenomenon may also be characteristic of certain colon cancer forms, while being detectable not only in the tumour but also in blood, which may be of clinical interest as regards either determining risk groups in terms of other localization malignant tumours development, especially colon cancer, or early diagnostics of the said diseases. However, relationship between clinical, phenotypic and molecular risk factors for EC and colon cancer needs further studying. The aim of research – to estimate MSI frequency in blood serum and colonic mucosal lining in patients with EC. Materials and methods. 342 patients with I – IV stage EC aged between 30 and 80 underwent MSI determining in tumour tissue, blood serum and colonic mucosa by means of polymerase chain reaction method using primers for microsatellite sequence (ВАТ-25, ВАТ-26. Colonic mucosal lining samples were obtained by colonoscopy prior to surgical intervention. Genomic DNA purification from blood serum was performed using DNA purification kit produced by Silex M Scientific and Production Company (Russia, in accordance with manufacturer's instructions. PCR was performed by the standard procedure using Tertsik-2 programmable thermal cycler produced by DNA – Technology LTD, Russia. The studies were carried out at Virola laboratory at Kharkiv Medical Academy of Postgraduate Education. Ethics and Bioethics Committee permit (minutes No.4 of 18.04.2013, Kharkiv Medical Academy of Postgraduate Education. The obtained digital study results were processed by means of conventional

  10. Bacterial colonization of colonic crypt mucous gel and disease activity in ulcerative colitis.

    LENUS (Irish Health Repository)

    Rowan, Fiachra

    2012-02-01

    OBJECTIVE: To optimize total bacterial 16S rRNA quantification in microdissected colonic crypts in healthy controls and patients with ulcerative colitis (UC) and to characterize the findings with disease activity. BACKGROUND: Microscopic and molecular techniques have recently converged to allow bacterial enumeration in remote anatomic locations [eg, crypt-associated mucous gel (CAMG)]. The aims of this study were to combine laser capture microdissection (LCM) and 16S rRNA-based quantitative polymerase chain reaction (qPCR) to determine total bacterial copy number in CAMG both in health and in UC and to characterize the findings with disease activity. METHODS: LCM was used to microdissect CAMG from colonic mucosal biopsies from controls (n = 20) and patients with acute (n = 10) or subacute (n = 10) UC. Pan-bacterial 16S rRNA copy number per millimeter square in samples from 6 locations across the large bowel was obtained by qPCR using Desulfovibrio desulfuricans as a reference strain. Copy numbers were correlated with the UC disease activity index (UCDAI) and the simple clinical colitis activity index (SCCAI). RESULTS: Bacterial colonization of CAMG was detectable in all groups. Copy numbers were significantly reduced in acute UC. In subacute colitis, there was a positive correlation between copy number and UCDAI and SCCAI in the ascending, transverse and sigmoid colon. CONCLUSIONS: This study describes a sensitive method of quantitatively assessing bacterial colonization of the colonic CAMG. A positive correlation was found between CAMG bacterial load and subacute disease activity in UC, whereas detectable bacterial load was reduced in acute UC.

  11. Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity.

    Directory of Open Access Journals (Sweden)

    Sya N Ukena

    2007-12-01

    Full Text Available Probiotics are proposed to positively modulate the intestinal epithelial barrier formed by intestinal epithelial cells (IECs and intercellular junctions. Disruption of this border alters paracellular permeability and is a key mechanism for the development of enteric infections and inflammatory bowel diseases (IBDs.To study the in vivo effect of probiotic Escherichia coli Nissle 1917 (EcN on the stabilization of the intestinal barrier under healthy conditions, germfree mice were colonized with EcN or K12 E. coli strain MG1655. IECs were isolated and analyzed for gene and protein expression of the tight junction molecules ZO-1 and ZO-2. Then, in order to analyze beneficial effects of EcN under inflammatory conditions, the probiotic was orally administered to BALB/c mice with acute dextran sodium sulfate (DSS induced colitis. Colonization of gnotobiotic mice with EcN resulted in an up-regulation of ZO-1 in IECs at both mRNA and protein levels. EcN administration to DSS-treated mice reduced the loss of body weight and colon shortening. In addition, infiltration of the colon with leukocytes was ameliorated in EcN inoculated mice. Acute DSS colitis did not result in an anion secretory defect, but abrogated the sodium absorptive function of the mucosa. Additionally, intestinal barrier function was severely affected as evidenced by a strong increase in the mucosal uptake of Evans blue in vivo. Concomitant administration of EcN to DSS treated animals resulted in a significant protection against intestinal barrier dysfunction and IECs isolated from these mice exhibited a more pronounced expression of ZO-1.This study convincingly demonstrates that probiotic EcN is able to mediate up-regulation of ZO-1 expression in murine IECs and confer protection from the DSS colitis-associated increase in mucosal permeability to luminal substances.

  12. The mucosal firewalls against commensal intestinal microbes.

    Science.gov (United States)

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

    2009-07-01

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

  13. Management of mucositis in oral irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Feber, T. [Cookridge Hospital, Leeds (United Kingdom)

    1996-10-01

    Mucositis significantly affects quality of life and tolerance of treatment in oral irradiation. Effective management of this complication is therefore very important. However, there is a scarcity of up-to-date oral care protocols, with most centres using ritualized regimens. The literature on oral rinses in radiation mucositis is at best inconclusive and at worst confusing. In this study, patients undergoing radical radiotherapy treatment (55-60 Gy in 4 weeks) to more than 50% of the oral cavity and oropharynx were randomized to a research based oral care protocol with either saline 0.9% or hydrogen peroxide 3.5 volumes (HP) as rinses. The results of this study show that, on average, the group receiving saline rinses appeared to do better on some outcomes than the group receiving HP. This suggests that frequent mechanical cleansing of the mouth may be more important than the antiseptic properties of a mouthwash. Antiseptic mouthwashes may be contra-indicated in radiation mucositis. In order to determine best practice in mucositis management, multicentre, multidisciplinary trials should be conducted. (Author).

  14. Management of mucositis in oral irradiation

    International Nuclear Information System (INIS)

    Feber, T.

    1996-01-01

    Mucositis significantly affects quality of life and tolerance of treatment in oral irradiation. Effective management of this complication is therefore very important. However, there is a scarcity of up-to-date oral care protocols, with most centres using ritualized regimens. The literature on oral rinses in radiation mucositis is at best inconclusive and at worst confusing. In this study, patients undergoing radical radiotherapy treatment (55-60 Gy in 4 weeks) to more than 50% of the oral cavity and oropharynx were randomized to a research based oral care protocol with either saline 0.9% or hydrogen peroxide 3.5 volumes (HP) as rinses. The results of this study show that, on average, the group receiving saline rinses appeared to do better on some outcomes than the group receiving HP. This suggests that frequent mechanical cleansing of the mouth may be more important than the antiseptic properties of a mouthwash. Antiseptic mouthwashes may be contra-indicated in radiation mucositis. In order to determine best practice in mucositis management, multicentre, multidisciplinary trials should be conducted. (Author)

  15. Nutrition and Gut Mucositis in Pediatric Oncology

    DEFF Research Database (Denmark)

    Pontoppidan, Peter Erik Lotko

    Childhood malignancies are the second most common cause of death in children. A major limitation of current therapies is the high toxicity. Alimentary tract toxicity (mucositis) is associated with increased risk of complication such as infections that may lead to death. In relation to HSCT, mucos...

  16. Can the oral microflora affect oral ulcerative mucositis?

    NARCIS (Netherlands)

    Laheij, A.M.G.A.; de Soet, J.J.

    2014-01-01

    Purpose of review: Oral mucositis is one of the most prevalent toxicities after hematopoietic stem cell transplantation. Mucositis is initiated by the chemotherapy or radiotherapy preceding the transplantation. It is commonly accepted that microorganisms play a role in the process of oral mucositis.

  17. The postnatal development of the mucosal immune system and mucosal tolerance in domestic animals

    OpenAIRE

    Bailey , Mick; Haverson , Karin

    2006-01-01

    International audience; The mucosal immune system is exposed to a range of antigens associated with pathogens, to which it must mount active immune responses. However, it is also exposed to a large number of harmless antigens associated with food and with commensal microbial flora, to which expression of active, inflammatory immune responses to these antigens is undesirable. The mucosal immune system must contain machinery capable of evaluating the antigens to which it is exposed and mounting...

  18. Neutrophil Interactions with Epithelial Expressed ICAM-1 Enhances Intestinal Mucosal Wound Healing

    Science.gov (United States)

    Sumagin, R; Brazil, JC; Nava, P; Nishio, H; Alam, A; Luissint, AC; Weber, DA; Neish, AS; Nusrat, A; Parkos, CA

    2015-01-01

    A characteristic feature of gastrointestinal tract inflammatory disorders, such as inflammatory bowel disease, is polymorphonuclear neutrophil (PMN) transepithelial migration (TEM) and accumulation in the gut lumen. PMN accumulation within the intestinal mucosa contributes to tissue injury. While epithelial infiltration by large numbers of PMNs results in mucosal injury, we found that PMN interactions with luminal epithelial membrane receptors may also play a role in wound healing. Intercellular adhesion molecule-1 (ICAM-1) is a PMN ligand that is upregulated on apical surfaces of intestinal epithelial cells under inflammatory conditions. In our study, increased expression of ICAM-1 resulted in enhanced PMN binding to the apical epithelium, which was associated with reduced PMN apoptosis. Following TEM, PMN adhesion to ICAM-1 resulted in activation of Akt and β-catenin signaling, increased epithelial-cell proliferation, and wound healing. Such responses were ICAM-1 dependent as engagement of epithelial ICAM-1 by antibody-mediated cross-linking yielded similar results. Furthermore, using an in-vivo biopsy-based, colonic-mucosal-injury model, we demonstrated epithelial ICAM-1 plays an important role in activation of epithelial Akt and β-catenin signaling and wound healing. These findings suggest that post-migrated PMNs within the intestinal lumen can regulate epithelial homeostasis, thereby identifying ICAM-1 as a potential therapeutic target for promoting mucosal wound healing. PMID:26732677

  19. Neutrophil interactions with epithelial-expressed ICAM-1 enhances intestinal mucosal wound healing.

    Science.gov (United States)

    Sumagin, R; Brazil, J C; Nava, P; Nishio, H; Alam, A; Luissint, A C; Weber, D A; Neish, A S; Nusrat, A; Parkos, C A

    2016-09-01

    A characteristic feature of gastrointestinal tract inflammatory disorders, such as inflammatory bowel disease, is polymorphonuclear neutrophil (PMN) transepithelial migration (TEM) and accumulation in the gut lumen. PMN accumulation within the intestinal mucosa contributes to tissue injury. Although epithelial infiltration by large numbers of PMNs results in mucosal injury, we found that PMN interactions with luminal epithelial membrane receptors may also play a role in wound healing. Intercellular adhesion molecule-1 (ICAM-1) is a PMN ligand that is upregulated on apical surfaces of intestinal epithelial cells under inflammatory conditions. In our study, increased expression of ICAM-1 resulted in enhanced PMN binding to the apical epithelium, which was associated with reduced PMN apoptosis. Following TEM, PMN adhesion to ICAM-1 resulted in activation of Akt and β-catenin signaling, increased epithelial-cell proliferation, and wound healing. Such responses were ICAM-1 dependent as engagement of epithelial ICAM-1 by antibody-mediated cross-linking yielded similar results. Furthermore, using an in-vivo biopsy-based, colonic-mucosal-injury model, we demonstrated epithelial ICAM-1 has an important role in activation of epithelial Akt and β-catenin signaling and wound healing. These findings suggest that post-migrated PMNs within the intestinal lumen can regulate epithelial homeostasis, thereby identifying ICAM-1 as a potential therapeutic target for promoting mucosal wound healing.

  20. Evaluation of capsule endoscopy to detect mucosal lesions associated with gastrointestinal bleeding in dogs.

    Science.gov (United States)

    Davignon, D L; Lee, A C Y; Johnston, A N; Bowman, D D; Simpson, K W

    2016-03-01

    The objective of this study was to examine the utility of capsule endoscopy to detect mucosal abnormalities in dogs with gastrointestinal haemorrhage. Capsules were administered to 2 healthy controls and 8 patients with gastrointestinal haemorrhage. Images were evaluated for quality, gastric emptying time, small intestinal transit time and presence of lesions. There were no adverse effects of capsule endoscopy in dogs weighing from 7·7 to 58 kg. The capsule traversed the entire gastrointestinal tract in 5 of 8 patients, with high quality images obtained in the stomach and small intestine. Gastric emptying time and small intestinal transit time ranged from 1 to 270 and 15 to 180 minutes, respectively. In 3 of 8 patients, the capsule remained in the stomach despite pro-kinetics. Gastric lesions included mild haemorrhage and pinpoint erosion (4 of 8), a mass (1) and thickened bleeding pyloric mucosa (2). Two of 3 dogs with capsule retention had gastric lesions. Intestinal lesions included a healing duodenal ulcer, abnormal villi, ileal ulceration and colonic bleeding. Lesions identified by capsule endoscopy were considered a significant source of haemorrhage in 4 of 7 dogs with active bleeding. The relevance of pinpoint gastric mucosal erosions to blood loss is unclear. Capsule endoscopy can enable the non-invasive detection of gastric and small intestinal mucosal lesions in dogs presenting for evaluation of gastrointestinal bleeding. © 2016 British Small Animal Veterinary Association.

  1. Essential role of the electroneutral Na+-HCO3- cotransporter NBCn1 in murine duodenal acid-base balance and colonic mucus layer build-up in vivo.

    Science.gov (United States)

    Singh, Anurag Kumar; Xia, Weiliang; Riederer, Brigitte; Juric, Marina; Li, Junhua; Zheng, Wen; Cinar, Ayhan; Xiao, Fang; Bachmann, Oliver; Song, Penghong; Praetorius, Jeppe; Aalkjaer, Christian; Seidler, Ursula

    2013-04-15

    Duodenal epithelial cells need efficient defence strategies during gastric acidification of the lumen, while colonic mucosa counteracts damage by pathogens by building up a bacteria-free adherent mucus layer. Transport of HCO3(-) is considered crucial for duodenal defence against acid as well as for mucus release and expansion, but the transport pathways involved are incompletely understood. This study investigated the significance of the electroneutral Na(+)-HCO3(-) cotransporter NBCn1 for duodenal defence against acid and colonic mucus release. NBCn1 was localized to the basolateral membrane of duodenal villous enterocytes and of colonic crypt cells, with predominant expression in goblet cells. Duodenal villous enterocyte intracellular pH was studied before and during a luminal acid load by two-photon microscopy in exteriorized, vascularly perfused, indicator (SNARF-1 AM)-loaded duodenum of isoflurane-anaesthetized, systemic acid-base-controlled mice. Acid-induced HCO3(-) secretion was measured in vivo by single-pass perfusion and pH-stat titration. After a luminal acid load, NBCn1-deficient duodenocytes were unable to recover rapidly from intracellular acidification and could not respond adequately with protective HCO3(-) secretion. In the colon, build-up of the mucus layer was delayed, and a decreased thickness of the adherent mucus layer was observed, suggesting that basolateral HCO3(-) uptake is essential for optimal release of mucus. The electroneutral Na(+)-HCO3(-) cotransporter NBCn1 displays a differential cellular distribution in the murine intestine and is essential for HCO3(-)-dependent mucosal protective functions, such as recovery of intracellular pH and HCO3(-) secretion in the duodenum and secretion of mucus in the colon.

  2. CT in colon cancer

    International Nuclear Information System (INIS)

    Fujita, Nobuyuki; Hasegawa, Takashi; Kubo, Kozo; Ogawa, Hajime; Sato, Yukihiko; Tomita, Masayoshi; Hanawa, Makoto; Matsuzawa, Tohru; Nishioka, Ken

    1990-01-01

    CT pictures from 59 lesions of advanced colon cancer including rectal cancer were reviewed to evaluate a role of CT in preoperative staging diagnosis. CT findings were recorded following general rules for clinical and pathological studies on cancer of colon rectum and anus, proposed by Japanese society for cancer of colon and rectum. Tumors were detected in 90% of advanced colon cancers. Sensitivity in local extension (S factor) was 58.0%. Sensitivity in lymphonode involvement (N factor) was 50.0%. Sensitivity in final staging diagnosis, dividing colon cancer into two groups below st II and above st III, was 63.3%. Further study should be necessitated to provide useful information for preoperative staging diagnosis of colon cancer. (author)

  3. An Act of Colonization

    DEFF Research Database (Denmark)

    Rasmussen, Anders Bo

    When Gideon Welles, U.S. Secretary of the Navy, sat down to write his diary entry on September 26, 1862, his thoughts turned once more to colonization. President Lincoln was an ardent proponent of colonization, “the government-promoted settlement of black Americans in Africa or some other location....... Croix. Thus, when the Lincoln administration seriously considered colonization plans in 1862, Danish Charge d’Affaires Waldemar Raasløff offered free transport for freedmen to the Caribbean island, where there was a “distinct lack of laborers.” As a small first step towards colonization, Denmark...

  4. Colon cancer screening

    Science.gov (United States)

    Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

  5. Intestinal Colonization Dynamics of Vibrio cholerae.

    Directory of Open Access Journals (Sweden)

    Salvador Almagro-Moreno

    2015-05-01

    Full Text Available To cause the diarrheal disease cholera, Vibrio cholerae must effectively colonize the small intestine. In order to do so, the bacterium needs to successfully travel through the stomach and withstand the presence of agents such as bile and antimicrobial peptides in the intestinal lumen and mucus. The bacterial cells penetrate the viscous mucus layer covering the epithelium and attach and proliferate on its surface. In this review, we discuss recent developments and known aspects of the early stages of V. cholerae intestinal colonization and highlight areas that remain to be fully understood. We propose mechanisms and postulate a model that covers some of the steps that are required in order for the bacterium to efficiently colonize the human host. A deeper understanding of the colonization dynamics of V. cholerae and other intestinal pathogens will provide us with a variety of novel targets and strategies to avoid the diseases caused by these organisms.

  6. Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: need for mucosal viral load measurement.

    Science.gov (United States)

    Ciccocioppo, Rachele; Racca, Francesca; Paolucci, Stefania; Campanini, Giulia; Pozzi, Lodovica; Betti, Elena; Riboni, Roberta; Vanoli, Alessandro; Baldanti, Fausto; Corazza, Gino Roberto

    2015-02-14

    To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD). A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated. All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/10(5) cells) than in non-refractory (HCMV 0 and EBV 6 copies/10(5) cells; P diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications. Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.

  7. Colonization of the oral cavity by probiotic bacteria.

    Science.gov (United States)

    Ravn, I; Dige, I; Meyer, R L; Nyvad, B

    2012-01-01

    The aim of this study was to investigate if three probiotic bacteria present in the milk product Cultura Dofilus® naturell could be detected in saliva and on oral mucosal surfaces, and if they colonized dental surfaces in situ in 8 caries-inactive individuals after 8 daily exposures to the milk product for up to 3 days. Bacteria were identified by fluorescence in situ hybridization and confocal laser scanning microscopy. While probiotic bacteria were present sporadically in the oral cavity on mucosal surfaces and in saliva after 3 days of frequent use of the probiotic milk, they were not detected on dental surfaces. Probiotic bacteria may thus contribute to general oral health, but their potential role in biofilm-induced dental diseases remains unclear. Copyright © 2012 S. Karger AG, Basel.

  8. Helicobacter pylori coinfection is a confounder, modulating mucosal inflammation in oral submucous fibrosis

    Directory of Open Access Journals (Sweden)

    Rajendran R

    2009-01-01

    Full Text Available The oral cavity has been considered a potential reservoir for Helicobacter pylori (H pylori , from where the organism causes recurrent gastric infections. Aim: With this case-control study we tried to evaluate the role of H pylori in the etiology of mucosal inflammation, a condition that compounds the morbid state associated with oral submucous fibrosis (OSF. Materials and Methods : Subjects ( n = 150 were selected following institutional regulations on sample collection and grouped into test cases and positive and negative controls based on the presence of mucosal fibrosis and inflammation. The negative controls had none of the clinical signs. All patients underwent an oral examination as well as tests to assess oral hygiene/periodontal disease status; a rapid urease test (RUT of plaque samples was also done to estimate the H pylori bacterial load. We used univariate and mutivariate logistic regression for statistical analysis of the data and calculated the odds ratios to assess the risk posed by the different variables. Results : The RUT results differed significantly between the groups, reflecting the variations in the bacterial loads in each category. The test was positive in 52% in the positive controls (where nonspecific inflammation of oral mucosa was seen unassociated with fibrosis, in 46% of the test cases, and in 18% of the negative controls (healthy volunteers (χ2 = 13.887; P < 0.01. A positive correlation was seen between the oral hygiene/periodontal disease indices and RUT reactivity in all the three groups. Conclusions: The contribution of the H pylori in dental plaque to mucosal inflammation and periodontal disease was significant. Logistic regression analysis showed gastrointestinal disease and poor oral hygiene as being the greatest risk factors for bacterial colonization, irrespective of the subject groups. A positive correlation exists between RUT reactivity and the frequency of mucosal inflammation.

  9. CT Findings of Colonic Complications Associated with Colon Cancer

    International Nuclear Information System (INIS)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang Jin

    2010-01-01

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer

  10. CT Findings of Colonic Complications Associated with Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang Jin [Cheonan Hospital, Soonchunhyang University, Cheonan (Korea, Republic of)

    2010-04-15

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer.

  11. Colon and rectal cancer

    International Nuclear Information System (INIS)

    Saldombide, L.; Cordoba, A.

    2010-01-01

    This study is about the diagnosis, therapy and monitoring of colon cancer. The techniques used are the endoscopy with biopsy in the pre and post operative colon surgery, abdominal ultrasound, chest X-ray studies of hemogram as well as liver and renal function

  12. Colon of the rat

    International Nuclear Information System (INIS)

    Lindstroem, C.G.; Rosengren, J.-E.; Fork, F.-T.

    1979-01-01

    The anatomy and radiologic appearance of the colon in rats are described on the basis of 300 animals treated with carcinogenic agents and 40 normal rats. The macroscopic and microscopic appearance of the mucosa varies in the different parts of the colon. Lymphoid plaques are normal structures. The results justify a new anatomic nomenclature. (Auth.)

  13. Dermoscopic appearance of an amelanotic mucosal melanoma

    Science.gov (United States)

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

    2016-01-01

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

  14. Bladder Mucosal Graft Vaginoplasty: A Case Report.

    Science.gov (United States)

    Chiaramonte, Cinzia; Vestri, Elettra; Tripi, Flavia; Giannone, Antonino Giulio; Cimador, Marcello; Cataliotti, Ferdinando

    2018-06-18

    Female vaginoplasty reconstruction, by choice, is usually performed with adjacent tissue. However in some clinical conditions such as high urogenital confluence sinus, cloacal malformation with extreme vaginal hypoplasia, local tissue may not be available. When vaginal replacement is performed in pediatric patients intestinal segments is preferred to non-operative procedures that require continuative dilations. However mucus production, malignant transformation risk and diversion colitis are important side effects. We present a nouvel technique for vaginoplasty in a female child presenting with an isolated urogenital sinus malformation without virilization. The patient at 20 months underwent vaginoplasty using tubularized bladder mucosal graft. Surgical procedure was devoid of complications. Pubertal development occurred at age of 15. She underwent regular follow up until 18 years of age. At this age we performed clinical evaluation: absence of vaginal introitus stenosis and good cosmetic results were observed. Then she underwent vaginoscopy with multiple biopsies. Pathology examination of the bladder mucosal graft evidenced a normal structure of the mucosa, with a stratified squamous epithelium. Different techniques are taken into account for vaginal reconstruction according to the severity and to the type of malformation. We describe the use of bladder mucosal graft with favorable results after long term follow-up. Copyright © 2018. Published by Elsevier Inc.

  15. Brain-gut axis and mucosal immunity: a perspective on mucosal psychoneuroimmunology.

    LENUS (Irish Health Repository)

    Shanahan, F

    2012-02-03

    The role of the brain-gut axis has traditionally been investigated in relation to intestinal motility, secretion, and vascularity. More recently, the concept of brain-gut dialogue has extended to the relationship between the nervous system and mucosal immune function. There is compelling evidence for a reciprocal or bi-directional communication between the immune system and the neuroendocrine system. This is mediated, in part, by shared ligands (chemical messengers) and receptors that are common to the immune and nervous systems. Although the concept of psychoneuroimmunology and neuroimmune cross-talk has been studied primarily in the context of the systemic immune system, it is likely to have special significance in the gut. The mucosal immune system is anatomically, functionally, and operationally distinct from the systemic immune system and is subject to independent regulatory signals. Furthermore, the intestinal mucosal immune system operates in a local milieu that depends on a dense innervation for its integrity, with juxtaposition of neuroendocrine cells and mucosal immune cells. An overview of evidence for the biologic plausibility of a brain-gut-immune axis is presented and its potential relevance to mucosal inflammatory disorders is discussed.

  16. Peripheral and central P2X3 receptor contributions to colon mechanosensitivity and hypersensitivity in the mouse

    Science.gov (United States)

    Shinoda, Masamichi; Feng, Bin; Gebhart, G. F.

    2009-01-01

    Background & Aims Irritable bowel syndrome is characterized by altered sensory qualities, namely discomfort/pain and colorectal hypersensitivity. In mice, we examined the role of P2X3 receptors in colon mechanosensitivity and intracolonic zymosan-produced hypersensitivity, a model of persistent colon hypersensitivity without colon inflammation. Methods The visceromotor response (VMR) to colon distension (15 – 60 mmHg) was determined before and after intracolonic saline or zymosan (30 mg/mL, 0.1 mL, daily for 3 days) treatment. Colon pathology and intracolonic ATP release was assessed in parallel experiments. To examine P2X3 receptor contributions to colon mechanosensation and hypersensitivity, electrophysiological experiments were performed using an in vitro colon-pelvic nerve preparation. Results VMRs to distension were significantly reduced in P2X3+/−and P2X3−/− mice relative to wildtype mice. Colon hypersensitivity produced by zymosan was virtually absent in P2X3−/− relative to wildtype or P2X3+/− mice. Intralumenal release of the endogenous P2X receptor ligand ATP did not differ between wildtype and P2X3−/− mice or change after intracolonic zymosan treatment. Responses of muscular and muscular-mucosal pelvic nerve afferents to mechanical stretch did not differ between P2X3−/− and wildtype mice. Both muscular and muscular-mucosal afferents in wildtype mice sensitized to application of an inflammatory soup, whereas only muscular-mucosal afferents did so in P2X3−/− mice. Conclusions These results suggest differential roles for peripheral and central P2X3 receptors in colon mechanosensory transduction and hypersensitivity. PMID:19549524

  17. Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model.

    Directory of Open Access Journals (Sweden)

    Takeshi Yamamoto

    Full Text Available The prevalence of food allergy (FA has increased in developed countries over the past few decades. However, no effective drug therapies are currently available. Therefore, we investigated cholinergic anti-inflammatory pathway as a regulatory system to ameliorate disrupted mucosal immune homeostasis in the gut based on the pathophysiological elucidation of mucosal mast cells (MMCs in a murine FA model. BALB/c mice sensitized with ovalbumin received repeated oral ovalbumin for the development of FA. FA mice developed severe allergic diarrhea and exhibited enhanced type 2 helper T (Th2 cell immune responses in both systemic immunity and mucosal immunity, along with MMCs hyperplasia in the colon. MMCs were localized primarily in the strategic position of the mucosal epithelium. Furthermore, the allergic symptoms did not develop in p85α disrupted phosphoinositide-3 kinase-deficient mice that lacked mast cells in the gut. Vagal stimulation by 2-deoxy-D-glucose and drug treatment with nicotinic ACh receptor (nAChR agonists (nicotine and α7 nAChR agonist GTS-21 alleviated the allergic symptoms in the FA mice. Nicotine treatment suppressed MMCs hyperplasia, enhanced MPO and upregulated mRNA expression of Th1 and Th2 cytokines in the FA mice colon. MMCs, which are negatively regulated by α7 nAChRs, were often located in close proximity to cholinergic CGRP-immunoreactive nerve fibers in the FA mice colon. The present results reveal that the cholinergic neuroimmune interaction via α7 nAChRs on MMCs is largely involved in maintaining intestinal immune homeostasis and can be a target for a new therapy against mucosal immune diseases with homeostatic disturbances such as FA.

  18. Enhanced mucosal re-epithelialization induced by short chain fatty acids in experimental colitis

    Directory of Open Access Journals (Sweden)

    Aguilar-Nascimento J.E.

    1999-01-01

    Full Text Available The short chain fatty acids (SCFA are the best nutrients for the colonocytes. Glucose is poorly used as a fuel but may be transformed into SCFA by colonic bacteria. The aim of this study was to investigate the effect of SCFA or glucose on experimental colitis. Colitis was induced in 30 Wistar rats by colonic instillation of 4% acetic acid. Five days later they were randomized to receive twice a day colonic lavage containing saline (controls, N = 10, 10% hypertonic glucose (N = 10 or SCFA (N = 10 until day 8 when they were killed. At autopsy, the colon was removed and weighed and the mucosa was evaluated macro- and microscopically and stripped out for DNA assay. Data are reported as mean ± SD or median [range] as appropriate. All animals lost weight but there was no difference between groups. Colon weight was significantly lower in the SCFA group (3.8 ± 0.5 g than in the control (5.3 ± 2.1 g and glucose (5.2 ± 1.3 g groups (P<0.05. Macroscopically, the severity of inflammation was less in SCFA (grade 2 [1-5] than in control (grade 9 [4-10] and glucose-treated (grade 9 [2-10] animals (P<0.01. Microscopically, ulceration of the mucosa was more severe in the glucose and control groups than in the SCFA group. The DNA content of the mucosa of SCFA-treated animals (8.2 [5.0-20.2] mg/g of tissue was higher than in glucose-treated (5.1 [4.2-8.5] mg/g of tissue; P<0.01 and control (6.2 [4.5-8.9] mg/g of tissue; P<0.05 animals. We conclude that SCFA may enhance mucosal re-epithelialization in experimental colitis, whereas hypertonic glucose is of no benefit.

  19. Streptococcus pneumoniae biofilm formation and dispersion during colonization and disease

    Science.gov (United States)

    Chao, Yashuan; Marks, Laura R.; Pettigrew, Melinda M.; Hakansson, Anders P.

    2015-01-01

    Streptococcus pneumoniae (the pneumococcus) is a common colonizer of the human nasopharynx. Despite a low rate of invasive disease, the high prevalence of colonization results in millions of infections and over one million deaths per year, mostly in individuals under the age of 5 and the elderly. Colonizing pneumococci form well-organized biofilm communities in the nasopharyngeal environment, but the specific role of biofilms and their interaction with the host during colonization and disease is not yet clear. Pneumococci in biofilms are highly resistant to antimicrobial agents and this phenotype can be recapitulated when pneumococci are grown on respiratory epithelial cells under conditions found in the nasopharyngeal environment. Pneumococcal biofilms display lower levels of virulence in vivo and provide an optimal environment for increased genetic exchange both in vitro and in vivo, with increased natural transformation seen during co-colonization with multiple strains. Biofilms have also been detected on mucosal surfaces during pneumonia and middle ear infection, although the role of these biofilms in the disease process is debated. Recent studies have shown that changes in the nasopharyngeal environment caused by concomitant virus infection, changes in the microflora, inflammation, or other host assaults trigger active release of pneumococci from biofilms. These dispersed bacteria have distinct phenotypic properties and transcriptional profiles different from both biofilm and broth-grown, planktonic bacteria, resulting in a significantly increased virulence in vivo. In this review we discuss the properties of pneumococcal biofilms, the role of biofilm formation during pneumococcal colonization, including their propensity for increased ability to exchange genetic material, as well as mechanisms involved in transition from asymptomatic biofilm colonization to dissemination and disease of otherwise sterile sites. Greater understanding of pneumococcal biofilm

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

    Science.gov (United States)

    Wilson, Heather L; Obradovic, Milan R

    2015-07-01

    The majority of lymphocytes activated at mucosal sites receive instructions to home back to the local mucosa, but a portion also seed distal mucosa sites. By seeding distal sites with antigen-specific effector or memory lymphocytes, the foundation is laid for the animal's mucosal immune system to respond with a secondary response should to this antigen be encountered at this site in the future. The common mucosal immune system has been studied quite extensively in rodent models but less so in large animal models such as the pig. Reasons for this paucity of reported induction of the common mucosal immune system in this species may be that distal mucosal sites were examined but no induction was observed and therefore it was not reported. However, we suspect that the majority of investigators simply did not sample distal mucosal sites and therefore there is little evidence of immune response induction in the literature. It is our hope that more pig immunologists and infectious disease experts who perform mucosal immunizations or inoculations on pigs will sample distal mucosal sites and report their findings, whether results are positive or negative. In this review, we highlight papers that show that immunization/inoculation using one route triggers mucosal immune system induction locally, systemically, and within at least one distal mucosal site. Only by understanding whether immunizations at one site triggers immunity throughout the common mucosal immune system can we rationally develop vaccines for the pig, and through these works we can gather evidence about the mucosal immune system that may be extrapolated to other livestock species or humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Probiotic supplements and debridement of peri-implant mucositis

    DEFF Research Database (Denmark)

    Hallström, Hadar; Lindgren, Susann; Widén, Cecilia

    2016-01-01

    OBJECTIVE: The aim of this double-blind randomized placebo-controlled trial was to evaluate the effects of probiotic supplements in adjunct to conventional management of peri-implant mucositis. MATERIALS AND METHODS: Forty-nine adult patients with peri-implant mucositis were consecutively recruited...... debridement and oral hygiene reinforcement resulted in clinical improvement of peri-implant mucositis and a reduction in cytokine levels. Probiotic supplements did not provide added benefit to placebo....

  2. Chitosan-Based Nanoparticles for Mucosal Delivery of RNAi Therapeutics

    DEFF Research Database (Denmark)

    Martirosyan, Alina; Olesen, Morten Jarlstad; Howard, Kenneth A.

    2014-01-01

    of the polysaccharide chitosan have been used to facilitate delivery of siRNA across mucosal surfaces following local administration. This chapter describes the mucosal barriers that need to be addressed in order to design an effective mucosal delivery strategy and the utilization of the mucoadhesive properties...... of chitosan. Focus is given to preparation methods and the preclinical application of chitosan nanoparticles for respiratory and oral delivery of siRNA....

  3. The Probiotic Compound VSL#3 Modulates Mucosal, Peripheral, and Systemic Immunity Following Murine Broad-Spectrum Antibiotic Treatment

    Directory of Open Access Journals (Sweden)

    Ira Ekmekciu

    2017-05-01

    Full Text Available There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, and L. delbrueckii subsp. Bulgaricus in reversing immunological effects of microbiota depletion as compared to reassociation with a complex murine microbiota. To address this, conventional mice were subjected to broad-spectrum antibiotic therapy for 8 weeks and perorally reassociated with either VSL#3 bacteria or a complex murine microbiota. VSL#3 recolonization resulted in restored CD4+ and CD8+ cell numbers in the small and large intestinal lamina propria as well as in B220+ cell numbers in the former, whereas probiotic intervention was not sufficient to reverse the antibiotic induced changes of respective cell populations in the spleen. However, VSL#3 application was as efficient as complex microbiota reassociation to attenuate the frequencies of regulatory T cells, activated dendritic cells and memory/effector T cells in the small intestine, colon, mesenteric lymph nodes, and spleen. Whereas broad-spectrum antibiotic treatment resulted in decreased production of cytokines such as IFN-γ, IL-17, IL-22, and IL-10 by CD4+ cells in respective immunological compartments, VSL#3 recolonization was sufficient to completely recover the expression of the anti-inflammatory cytokine IL-10 without affecting pro-inflammatory mediators. In summary, the probiotic compound VSL#3 has an extensive impact on mucosal, peripheral, and

  4. Scoring irradiation mucositis in head and neck cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Spijkervet, F.K.L.; Panders, A.K. (Departments of Oral and Maxillofacial Surgery, University Hospital Groningen (Netherlands)); Saene, H.K.F. van (Medical Microbiology, University of Liverpool (UK)); Vermey, A. (Department of Surgery Oncology Division, University Hospital Groningen (Netherlands)); Mehta, D.M. (Department of Radiotherapy, University Hospital Groningen (Netherlands))

    1989-01-01

    Irradiation mucositis is defined as an inflammatory-like process of the oropharyngeal mucosa following therapeutic irradiation of patients who have head and neck cancer. Clinically, it is a serious side effect because severe mucositis can cause generalized problems (weight loss, nasogastic tube feedings) and interferes with the well-being of the patient seriously. Grading mucositis is important for the evaluation of preventive and therapeutic measures. The object of this study was to develop a scoring method based on local mucositis signs only. Four clinical local signs of mucositis were used in this score: white discoloration, erythema, pseudomembranes and ulceration. Mucositis of the oral cavity was calcualted during conventional irradiation protocol for 8 distinguishable areas using the 4 signs and their extent. A prospective evaluation of this method in 15 irradiated head and neck cancer patients displayed an S-curve reflecting a symptomless first irradiation week, followed by a rapid and steady increase of white discoloration, erythema and pseudomembranes during the second and third week. Oral candidiasis, generalized symptoms such as weight loss and the highest mucositis scores were seen after 3 weeks irradiation. The novel mucositis scoring method may be of value in studying the effect of hygiene programs, topical application of disinfectans or antibiotics on oral mucositis. (author).

  5. Scoring irradiation mucositis in head and neck cancer patients

    International Nuclear Information System (INIS)

    Spijkervet, F.K.L.; Panders, A.K.; Saene, H.K.F. van; Vermey, A.; Mehta, D.M.

    1989-01-01

    Irradiation mucositis is defined as an inflammatory-like process of the oropharyngeal mucosa following therapeutic irradiation of patients who have head and neck cancer. Clinically, it is a serious side effect because severe mucositis can cause generalized problems (weight loss, nasogastic tube feedings) and interferes with the well-being of the patient seriously. Grading mucositis is important for the evaluation of preventive and therapeutic measures. The object of this study was to develop a scoring method based on local mucositis signs only. Four clinical local signs of mucositis were used in this score: white discoloration, erythema, pseudomembranes and ulceration. Mucositis of the oral cavity was calcualted during conventional irradiation protocol for 8 distinguishable areas using the 4 signs and their extent. A prospective evaluation of this method in 15 irradiated head and neck cancer patients displayed an S-curve reflecting a symptomless first irradiation week, followed by a rapid and steady increase of white discoloration, erythema and pseudomembranes during the second and third week. Oral candidiasis, generalized symptoms such as weight loss and the highest mucositis scores were seen after 3 weeks irradiation. The novel mucositis scoring method may be of value in studying the effect of hygiene programs, topical application of disinfectans or antibiotics on oral mucositis. (author)

  6. A Case of Sigmoid Colon Tuberculosis Mimicking Colon Cancer

    OpenAIRE

    Yu, Seong-Min; Park, Jong-Hwan; Kim, Min-Dae; Lee, Hee-Ryong; Jung, Peel; Ryu, Tae-Hyun; Choi, Seung-Ho; Lee, Il-Seon

    2012-01-01

    Tuberculosis of the sigmoid colon is a rare disorder. An 80-year-old man visited Bongseng Memorial Hospital for medical examination. A colonoscopy was performed, and a lesion in the sigmoid colon that was suspected to be colon cancer was found. A biopsy was performed, and tuberculous enteritis with chronic granulomatous inflammation was diagnosed. Intestinal tuberculosis is most frequent in the ileocecal area, followed by the ascending colon, transverse colon, duodenum, stomach, and sigmoid c...

  7. Environmental and mucosal microbiota and their role in childhood asthma.

    Science.gov (United States)

    Birzele, L T; Depner, M; Ege, M J; Engel, M; Kublik, S; Bernau, C; Loss, G J; Genuneit, J; Horak, E; Schloter, M; Braun-Fahrländer, C; Danielewicz, H; Heederik, D; von Mutius, E; Legatzki, A

    2017-01-01

    High microbial diversity in the environment has been associated with lower asthma risk, particularly in children exposed to farming. It remains unclear whether this effect operates through an altered microbiome of the mucosal surfaces of the airways. DNA from mattress dust and nasal samples of 86 school age children was analyzed by 454 pyrosequencing of the 16S rRNA gene fragments. Based on operational taxonomic units (OTUs), bacterial diversity and composition were related to farm exposure and asthma status. Farm exposure was positively associated with bacterial diversity in mattress dust samples as determined by richness (P = 8.1 × 10 -6 ) and Shannon index (P = 1.3 × 10 -5 ). Despite considerable agreement of richness between mattress and nasal samples, the association of richness with farming in nasal samples was restricted to a high gradient of farm exposure, that is, exposure to cows and straw vs no exposure at all. In mattress dust, the genera Clostridium, Facklamia, an unclassified genus within the family of Ruminococcaceae, and six OTUs were positively associated with farming. Asthma was inversely associated with richness [aOR = 0.48 (0.22-1.02)] and Shannon index [aOR = 0.41 (0.21-0.83)] in mattress dust and to a lower extent in nasal samples [richness aOR 0.63 = (0.38-1.06), Shannon index aOR = 0.66 (0.39-1.12)]. The stronger inverse association of asthma with bacterial diversity in mattress dust as compared to nasal samples suggests microbial involvement beyond mere colonization of the upper airways. Whether inhalation of metabolites of environmental bacteria contributes to this phenomenon should be the focus of future research. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Helicobacter pylori colonization critically depends on postprandial gastric conditions

    Science.gov (United States)

    Bücker, Roland; Azevedo-Vethacke, Marina; Groll, Claudia; Garten, Désirée; Josenhans, Christine; Suerbaum, Sebastian; Schreiber, Sören

    2012-01-01

    The risk of Helicobacter pylori infection is highest in childhood, but the colonization process of the stomach mucosa is poorly understood. We used anesthetized Mongolian gerbils to study the initial stages of H. pylori colonization. Prandial and postprandial gastric conditions characteristic of humans of different ages were simulated. The fraction of bacteria that reached the deep mucus layer varied strongly with the modelled postprandial conditions. Colonization success was weak with fast gastric reacidification typical of adults. The efficiency of deep mucus entry was also low with a slow pH decrease as seen in pH profiles simulating the situation in babies. Initial colonization was most efficient under conditions simulating the postprandial reacidification and pepsin activation profiles in young children. In conclusion, initial H. pylori colonization depends on age-related gastric physiology, providing evidence from an in vivo infection model that suggests an explanation why the bacterium is predominantly acquired in early childhood. PMID:23251780

  9. Diverticular colitis of the ascending colon preceding the onset of ulcerative colitis.

    Science.gov (United States)

    Maeshiro, Tatsuji; Hokama, Akira; Kinjo, Tetsu; Fujita, Jiro

    2014-06-30

    We present a case of diverticular colitis of the ascending colon preceding the onset of ulcerative colitis. A 58-year-old man presented with positive faecal occult blood test. Colonoscopy disclosed diverticular colitis of the ascending colon. After a year's follow-up, typical ulcerative colitis developed and diverticular colitis improved. Diverticular colitis is a newly established disorder of chronic segmental mucosal inflammation affected by diverticular disease. There is increasing recognition of such cases with diverticular colitis preceding ulcerative colitis. There may be a possible pathogenic relationship between the two diseases. 2014 BMJ Publishing Group Ltd.

  10. Primary Signet Ring Cell Carcinoma of Rectum Diagnosed by Boring Biopsy in Combination with Endoscopic Mucosal Resection

    Directory of Open Access Journals (Sweden)

    Yoshito Hirata

    2018-01-01

    Full Text Available A 46-year-old man with severe back pain visited our hospital. Magnetic resonance imaging revealed extensive bone metastasis and rectal wall thickness. Colonoscopy revealed circumferential stenosis with edematous mucosa, suggesting colon cancer. However, histological findings of biopsy specimens revealed inflammatory cells but no malignant cells. The patient underwent endoscopic ultrasound, which demonstrated edematous wall thickness without destruction of the normal layer structure. After unsuccessful detection of neoplastic cells by boring biopsies, we performed endoscopic mucosal resection followed by boring biopsies that finally revealed signet ring cell carcinoma. Herein, we present a case and provide a review of the literature.

  11. Oral mucosal lesions in denture wearers.

    Science.gov (United States)

    Jainkittivong, Aree; Aneksuk, Vilaiwan; Langlais, Robert P

    2010-03-01

    To determine the prevalence of oral mucosal lesions (OMLs) and denture-related mucosal lesions (DMLs) in denture wearers and to co-relate the prevalence with age, gender, type of denture and any systemic conditions. Dental records of 380 denture wearers were retrospectively reviewed for OMLs and DMLs. We found 45% of the denture wearers had DMLs and 60.8% had OMLs not related to denture wearing. Although the prevalence of DMLs was higher in complete denture wearers than in partial denture wearers (49% vs. 42.2%), this difference was not significant. The most common DMLs were traumatic ulcer (19.5%) and denture-induced stomatitis (18.1%). When analysed by type, traumatic ulcer, denture hyperplasia, frictional keratosis and candidiasis were more common in complete denture wearers, whereas denture-induced stomatitis was more common in partial denture wearers. Frictional keratosis was more common in men than in women. The prevalence of OMLs not related to denture wearing was higher in complete denture wearers than in partial denture wearers, and the most common OML was fissured tongue (27.6%). No association between DMLs and systemic conditions or xerostomic drugs was noted. No differences in the prevalence of DMLs in association with denture type were found. The prevalence of OMLs not related to denture wearing was higher in complete denture wearers than in partial denture wearers. This difference was affected by age, and the data were similar to the findings observed in the elderly.

  12. Carotenoids and colon cancer.

    Science.gov (United States)

    Slattery, M L; Benson, J; Curtin, K; Ma, K N; Schaeffer, D; Potter, J D

    2000-02-01

    Carotenoids have numerous biological properties that may underpin a role for them as chemopreventive agents. However, except for beta-carotene, little is known about how dietary carotenoids are associated with common cancers, including colon cancer. The objective of this study was to evaluate associations between dietary alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin and the risk of colon cancer. Data were collected from 1993 case subjects with first primary incident adenocarcinoma of the colon and from 2410 population-based control subjects. Dietary data were collected from a detailed diet-history questionnaire and nutrient values for dietary carotenoids were obtained from the US Department of Agriculture-Nutrition Coordinating Center carotenoid database (1998 updated version). Lutein was inversely associated with colon cancer in both men and women [odds ratio (OR) for upper quintile of intake relative to lowest quintile of intake: 0.83; 95% CI: 0.66, 1.04; P = 0.04 for linear trend]. The greatest inverse association was observed among subjects in whom colon cancer was diagnosed when they were young (OR: 0.66; 95% CI: 0.48, 0.92; P = 0.02 for linear trend) and among those with tumors located in the proximal segment of the colon (OR: 0.65; 95% CI: 0.51, 0.91; P lettuce, tomatoes, oranges and orange juice, carrots, celery, and greens. These data suggest that incorporating these foods into the diet may help reduce the risk of developing colon cancer.

  13. Glycoprotein expression by adenomatous polyps of the colon

    Science.gov (United States)

    Roney, Celeste A.; Xie, Jianwu; Xu, Biying; Jabour, Paul; Griffiths, Gary; Summers, Ronald M.

    2008-03-01

    Colon cancer is the second leading cause of cancer related deaths in the United States. Specificity in diagnostic imaging for detecting colorectal adenomas, which have a propensity towards malignancy, is desired. Adenomatous polyp specimens of the colon were obtained from the mouse model of colorectal cancer called adenomatous polyposis coli-multiple intestinal neoplasia (APC Min). Histological evaluation, by the legume protein Ulex europaeus agglutinin I (UEA-1), determined expression of the glycoprotein α-L-fucose. FITC-labelled UEA-1 confirmed overexpression of the glycoprotein by the polyps on fluorescence microscopy in 17/17 cases, of which 13/17 included paraffin-fixed mouse polyp specimens. In addition, FITC-UEA-1 ex vivo multispectral optical imaging of 4/17 colonic specimens displayed over-expression of the glycoprotein by the polyps, as compared to non-neoplastic mucosa. Here, we report the surface expression of α-L-fucosyl terminal residues by neoplastic mucosal cells of APC specimens of the mouse. Glycoprotein expression was validated by the carbohydrate binding protein UEA-1. Future applications of this method are the development of agents used to diagnose cancers by biomedical imaging modalities, including computed tomographic colonography (CTC). UEA-1 targeting to colonic adenomas may provide a new avenue for the diagnosis of colorectal carcinoma by CT imaging.

  14. Transgene vaccination using Ulex europaeus agglutinin I (UEA-1) for targeted mucosal immunization against HIV-1 envelope.

    Science.gov (United States)

    Wang, Xinhai; Kochetkova, Irina; Haddad, Asmahan; Hoyt, Teri; Hone, David M; Pascual, David W

    2005-05-31

    Receptor-mediated gene transfer using an M cell ligand has been shown to be an efficient method for mucosal DNA immunization. To investigate further into alternative M cell ligands, the plant lectin, Ulex europaeus agglutinin I (UEA-1), was tested. UEA-1 binds to human intestinal Caco-2 cells, and these cells can be transfected with poly-l-lysine (PL)-conjugated UEA-1 for expression of reporter cDNAs. When tested in vivo, mice nasally immunized with UEA-1-PL complexed to plasmid encoding HIV-1 envelope showed elevated systemic and mucosal antibody responses, and these were supported by tissue antibody-forming cells. Likewise, elevated envelope-specific CTLs were induced. Thus, UEA-1 mediated DNA delivery represents an alternative mucosal formulation for inducing humoral and cellular immunity against HIV-1.

  15. sup(99m)Tc-sucralfate scintigraphy and colonic disease

    International Nuclear Information System (INIS)

    George, A.; Merrick, M.V.; Palmer, K.R.; Millar, A.M.

    1987-01-01

    Sucralfate is an aluminium substituted disaccharide, binding at low pH to sites of ulceration in the gastrointestinal tract. Dawson et al (1985) reported that abdominal scans taken 12-24 hours after ingestion of sup(99m)Tc-sucralfate provide a range of normal appearances in healthy subjects and the pattern of ileal or colonic abnormalities in inflammatory bowel disease, surprising in view of the low binding affinity of sucralfate at ileonic pH. The authors have studied a series of 18 consecutive patients undergoing routine colonoscopy preceded by sup(99m)Tc-sucralfate scintigraphy. In vitro tests of isotope binding to parent molecule and absence of gastric mucosal uptake show that the disappointing results were not due to disruption of the sup(99m)Tc-sucralfate complex. It is suggested that labelled sucralfate attaches to luminal contents rather than adhering to mucosa, supported by the caecal 'hot spots' found in patients shown to have caecal pooling at colonoscopy and by observations that the one poorly prepared patient with pronounced faecal retention at time of endoscopy also had increased retention of radioactivity throughout the colon in the absence of mucosal abnormality. (U.K.)

  16. Sup(99m)Tc-sucralfate scintigraphy and colonic disease

    Energy Technology Data Exchange (ETDEWEB)

    George, A.; Merrick, M.V.; Palmer, K.R.; Millar, A.M.

    1987-09-05

    Sucralfate is an aluminium substituted disaccharide, binding at low pH to sites of ulceration in the gastrointestinal tract. Dawson et al (1985) reported that abdominal scans taken 12-24 hours after ingestion of sup(99m)Tc-sucralfate provide a range of normal appearances in healthy subjects and the pattern of ileal or colonic abnormalities in inflammatory bowel disease, surprising in view of the low binding affinity of sucralfate at ileonic pH. The authors have studied a series of 18 consecutive patients undergoing routine colonoscopy preceded by sup(99m)Tc-sucralfate scintigraphy. In vitro tests of isotope binding to parent molecule and absence of gastric mucosal uptake show that the disappointing results were not due to disruption of the sup(99m)Tc-sucralfate complex. It is suggested that labelled sucralfate attaches to luminal contents rather than adhering to mucosa, supported by the caecal 'hot spots' found in patients shown to have caecal pooling at colonoscopy and by observations that the one poorly prepared patient with pronounced faecal retention at time of endoscopy also had increased retention of radioactivity throughout the colon in the absence of mucosal abnormality. (U.K.).

  17. Mucosal Immune Regulation in Early Infancy: Monitoring and Intervention

    NARCIS (Netherlands)

    J. Hol (Jeroen)

    2011-01-01

    textabstractThe mucosal immune system of infants is dependent on the maintenance of mucosal homeostasis. Homeostasis results from the interaction between the mucosa and exogenous factors such as dietar and microbial agents. Induction and maintenance of homeostasis is a highly regluated system that

  18. Chemotherapy induced intestinal mucositis; from bench to bed

    NARCIS (Netherlands)

    B.A.E. Koning, de (Barbara)

    2008-01-01

    textabstractPart 1 focuses primarily on the pathophysiology of mucositis, in order to gain more insight different experimental mouse models were used. Chapter 2 describes mucositis induced by high dose doxorubicin (DOX)- treatment. DOX is a frequently used cytostatic drug in childhood cancer,

  19. Gastrointestinal mucosal abnormalities using videocapsule endoscopy in systemic sclerosis.

    Science.gov (United States)

    Marie, I; Antonietti, M; Houivet, E; Hachulla, E; Maunoury, V; Bienvenu, B; Viennot, S; Smail, A; Duhaut, P; Dupas, J-L; Dominique, S; Hatron, P-Y; Levesque, H; Benichou, J; Ducrotté, P

    2014-07-01

    To date, there are no large studies on videocapsule endoscopy in systemic sclerosis (SSc). Consequently, the prevalence and features of gastrointestinal mucosal abnormalities in SSc have not been determined. To determine both prevalence and characteristics of gastrointestinal mucosal abnormalities in unselected patients with SSc, using videocapsule endoscopy. To predict which SSc patients are at risk of developing potentially bleeding gastrointestinal vascular mucosal abnormalities. Videocapsule endoscopy was performed on 50 patients with SSc. Prevalence of gastrointestinal mucosal abnormalities was 52%. Potentially bleeding vascular mucosal lesions were predominant, including: watermelon stomach (34.6%), gastric and/or small intestinal telangiectasia (26.9%) and gastric and/or small intestinal angiodysplasia (38.5%). SSc patients with gastrointestinal vascular mucosal lesions more often exhibited: limited cutaneous SSc (P = 0.06), digital ulcers (P = 0.05), higher score of nailfold videocapillaroscopy (P = 0.0009), anaemia (P = 0.02), lower levels of ferritin (P correlation between gastrointestinal vascular mucosal lesions and presence of severe extra-digestive vasculopathy (digital ulcers and higher nailfold videocapillaroscopy scores). This latter supports the theory that SSc-related diffuse vasculopathy is responsible for both cutaneous and digestive vascular lesions. Therefore, we suggest that nailfold videocapillaroscopy may be a helpful test for managing SSc patients. In fact, nailfold videocapillaroscopy score should be calculated routinely, as it may result in identification of SSc patients at higher risk of developing potentially bleeding gastrointestinal vascular mucosal lesions. © 2014 John Wiley & Sons Ltd.

  20. The dietary polysaccharide maltodextrin promotes Salmonella survival and mucosal colonization in mice.

    Directory of Open Access Journals (Sweden)

    Kourtney P Nickerson

    Full Text Available In the latter half of the 20th century, societal and technological changes led to a shift in the composition of the American diet to include a greater proportion of processed, pre-packaged foods high in fat and carbohydrates, and low in dietary fiber (a "Western diet". Over the same time period, there have been parallel increases in Salmonella gastroenteritis cases and a broad range of chronic inflammatory diseases associated with intestinal dysbiosis. Several polysaccharide food additives are linked to bacterially-driven intestinal inflammation and may contribute to the pathogenic effects of a Western diet. Therefore, we examined the effect of a ubiquitous polysaccharide food additive, maltodextrin (MDX, on clearance of the enteric pathogen Salmonella using both in vitro and in vivo infection models. When examined in vitro, murine bone marrow-derived macrophages exposed to MDX had altered vesicular trafficking, suppressed NAPDH oxidase expression, and reduced recruitment of NADPH oxidase to Salmonella-containing vesicles, which resulted in persistence of Salmonella in enlarged Rab7+ late endosomal vesicles. In vivo, mice consuming MDX-supplemented water had a breakdown of the anti-microbial mucous layer separating gut bacteria from the intestinal epithelium surface. Additionally, oral infection of these mice with Salmonella resulted in increased cecal bacterial loads and enrichment of lamina propria cells harboring large Rab7+ vesicles. These findings indicate that consumption of processed foods containing the polysaccharide MDX contributes to suppression of intestinal anti-microbial defense mechanisms and may be an environmental priming factor for the development of chronic inflammatory disease.

  1. An endoscopic mucosal grading system is predictive of leak in stapled rectal anastomoses.

    Science.gov (United States)

    Sujatha-Bhaskar, Sarath; Jafari, Mehraneh D; Hanna, Mark; Koh, Christina Y; Inaba, Colette S; Mills, Steven D; Carmichael, Joseph C; Nguyen, Ninh T; Stamos, Michael J; Pigazzi, Alessio

    2018-04-01

    Anastomotic leak is a devastating postoperative complication following rectal anastomoses associated with significant clinical and oncological implications. As a result, there is a need for novel intraoperative methods that will help predict anastomotic leak. From 2011 to 2014, patient undergoing rectal anastomoses by colorectal surgeons at our institution underwent prospective application of intraoperative flexible endoscopy with mucosal grading. Retrospective review of patient medical records was performed. After creation of the colorectal anastomosis, application of a three-tier endoscopic mucosal grading system occurred. Grade 1 was defined as circumferentially normal appearing peri-anastomotic mucosa. Grade 2 was defined as ischemia or congestion involving 30% of the colon or rectal mucosa or ischemia/congestion involving both sides of the staple line. From 2011 to 2014, a total of 106 patients were reviewed. Grade 1 anastomoses were created in 92 (86.7%) patients and Grade 2 anastomoses were created in 10 (9.4%) patients. All 4 (3.8%) Grade 3 patients underwent immediate intraoperative anastomosis takedown and re-creation, with subsequent re-classification as Grade 1. Demographic and comorbidity data were similar between Grade 1 and Grade 2 patients. Anastomotic leak rate for the entire cohort was 12.2%. Grade 1 patients demonstrated a leak rate of 9.4% (9/96) and Grade 2 patients demonstrated a leak rate of 40% (4/10). Multivariate logistic regression associated Grade 2 classification with an increased risk of anastomotic leak (OR 4.09, 95% CI 1.21-13.63, P = 0.023). Endoscopic mucosal grading is a feasible intraoperative technique that has a role following creation of a rectal anastomosis. Identification of a Grade 2 or Grade 3 anastomosis should provoke strong consideration for immediate intraoperative revision.

  2. The analysis of bacterial culture in radiation mucositis

    International Nuclear Information System (INIS)

    Wen Zunbei; Su Deqing; Liang Yuxue

    2006-01-01

    Objective: To investigate pathogen dose existing or not in patients with radiation mucositis. Methods: From Juanary 2004 to August 2005, from 46 patients with radiation mucositis some pharynx secretion were taken for culture. Then they were treated with antibiotics selected by the cultured results and gargle. Results: 5 patients with grade 0 of radiation mucositis were with no cultured pathogen, and the results of some other patients with radiation mucositis include 8 cases of epiphyte, 1 cases of p. vulgaris and 3 cases of Staphylococcus. the positive rate is 29.2% (12/41); Conclusion: Some patients with radiation mucositis do exist pathogen, and we must slect antibiotics by the bacterial cultured results. (authors)

  3. NH4+ secretion in the avian colon. An actively regulated barrier to ammonium permeation of the colon mucosa

    DEFF Research Database (Denmark)

    Holtug, K.; Laverty, G.; Arnason, S.S.

    2009-01-01

    Experiments were designed to characterize an active, electrogenic transport of NH(4)(+) ions across the colonic epithelium of the domestic fowl (Gallus gallus). Colonic segments were isolated and stripped of underlying muscle. The mucosal epithelia were mounted in Ussing chambers and voltage......-clamped to measure the short-circuit currents (I(SC)) associated with transport. Bilateral addition of NH(4)(+) caused a dose-dependent outward current (negative I(SC)), with a Km of 34+/-8 mM and a maximal current response of 311+/-47 microA cm(-2) (12+/-2 microEq cm(-2) h(-1)). A similar effect was seen...... with unilateral addition of NH(4)(+) to the serosal (s) side, but not with mucosal (m) addition. Pre-treatment with 10(-4) M amiloride exposed a net outward (negative) I(SC), and serosal NH(4)(+) addition further increased this outward current with a Km of 53+/-24 mM. Decreasing the bath pH from 7.3 to 6.0 did...

  4. Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation

    Science.gov (United States)

    Tailford, Louise E.; Owen, C. David; Walshaw, John; Crost, Emmanuelle H.; Hardy-Goddard, Jemma; Le Gall, Gwenaelle; de Vos, Willem M.; Taylor, Garry L.; Juge, Nathalie

    2015-07-01

    The gastrointestinal mucus layer is colonized by a dense community of microbes catabolizing dietary and host carbohydrates during their expansion in the gut. Alterations in mucosal carbohydrate availability impact on the composition of microbial species. Ruminococcus gnavus is a commensal anaerobe present in the gastrointestinal tract of >90% of humans and overrepresented in inflammatory bowel diseases (IBD). Using a combination of genomics, enzymology and crystallography, we show that the mucin-degrader R. gnavus ATCC 29149 strain produces an intramolecular trans-sialidase (IT-sialidase) that cleaves off terminal α2-3-linked sialic acid from glycoproteins, releasing 2,7-anhydro-Neu5Ac instead of sialic acid. Evidence of IT-sialidases in human metagenomes indicates that this enzyme occurs in healthy subjects but is more prevalent in IBD metagenomes. Our results uncover a previously unrecognized enzymatic activity in the gut microbiota, which may contribute to the adaptation of intestinal bacteria to the mucosal environment in health and disease.

  5. Effect of gene time on acute radiation mucositis and dermatitis

    International Nuclear Information System (INIS)

    Li Suyan; Gao Li; Yin Weibo; Xu Guozhen; Xiao Guangli

    2002-01-01

    Objective: To evaluate the effect of recombinant human epidermal growth factor (Gene Time) on acute mucositis and dermatitis induced by radiation. Methods: 120 head and neck cancer patients were randomized into 3 groups: 1. Mucositis prophylactic application (MPA) group with control, 2. Mucositis therapeutic application (MTA) group with control and 3. Dermatitis therapeutic application (DTA) group with control. Prophylactic application of drug consisted of spraying the Gene Time preparation on the irradiated skin or mucous membrane as radiotherapy was being carried out. This was compared with control patients who received routine conventional skin care. Therapeutic application was started as grade I radiation mucositis or dermatitis appeared. The evaluation of acute radiation mucositis and dermatitis was done according to the systems proposed by RTOG or EORTC. Results: The results showed that in the MPA group, the rate of radiation mucositis at ≤10 Gy was 20% (4/20) as compared to the 70% (14/20) of the control (P = 0.004). During the course of radiation, the incidences of grade III, IV acute radiation mucositis and dermatitis were always lower than the control. In therapeutic application of Gene Time, the response rate of acute radiation mucositis was also better than the control (90% vs 50%) (P = 0.016) and that of acute dermatitis was similar (95% vs 50%) (P = 0.005). Moreover, the ≤3 d rate of healing of grade III dermatitis in the application group was 3/7 as compared to the 0/14 of the control. Conclusion: Prophylactic application of recombinant human epidermal growth factor is able to postpone the development of radiation mucositis. This preparation is also able to lower the incidence of grade III, IV mucositis and dermatitis both by therapeutic and prophylactic application in addition to the hastened healing of grade III dermatitis

  6. Deficient Pms2, ERCC1, Ku86, CcOI in field defects during progression to colon cancer.

    Science.gov (United States)

    Nguyen, Huy; Loustaunau, Cristy; Facista, Alexander; Ramsey, Lois; Hassounah, Nadia; Taylor, Hilary; Krouse, Robert; Payne, Claire M; Tsikitis, V Liana; Goldschmid, Steve; Banerjee, Bhaskar; Perini, Rafael F; Bernstein, Carol

    2010-07-28

    In carcinogenesis, the "field defect" is recognized clinically because of the high propensity of survivors of certain cancers to develop other malignancies of the same tissue type, often in a nearby location. Such field defects have been indicated in colon cancer. The molecular abnormalities that are responsible for a field defect in the colon should be detectable at high frequency in the histologically normal tissue surrounding a colonic adenocarcinoma or surrounding an adenoma with advanced neoplasia (well on the way to a colon cancer), but at low frequency in the colonic mucosa from patients without colonic neoplasia. Using immunohistochemistry, entire crypts within 10 cm on each side of colonic adenocarcinomas or advanced colonic neoplasias were found to be frequently reduced or absent in expression for two DNA repair proteins, Pms2 and/or ERCC1. Pms2 is a dual role protein, active in DNA mismatch repair as well as needed in apoptosis of cells with excess DNA damage. ERCC1 is active in DNA nucleotide excision repair. The reduced or absent expression of both ERCC1 and Pms2 would create cells with both increased ability to survive (apoptosis resistance) and increased level of mutability. The reduced or absent expression of both ERCC1 and Pms2 is likely an early step in progression to colon cancer. DNA repair gene Ku86 (active in DNA non-homologous end joining) and Cytochrome c Oxidase Subunit I (involved in apoptosis) had each been reported to be decreased in expression in mucosal areas close to colon cancers. However, immunohistochemical evaluation of their levels of expression showed only low to modest frequencies of crypts to be deficient in their expression in a field defect surrounding colon cancer or surrounding advanced colonic neoplasia. We show, here, our method of evaluation of crypts for expression of ERCC1, Pms2, Ku86 and CcOI. We show that frequency of entire crypts deficient for Pms2 and ERCC1 is often as great as 70% to 95% in 20 cm long areas

  7. Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients

    NARCIS (Netherlands)

    Saunders, Deborah P.; Epstein, Joel B.; Elad, Sharon; Allemano, Justin; Bossi, Paolo; van de Wetering, Marianne D.; Rao, Nikhil G.; Potting, Carin; Cheng, Karis K.; Freidank, Annette; Brennan, Michael T.; Bowen, Joanne; Dennis, Kristopher; Lalla, Rajesh V.

    2013-01-01

    The aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis (OM) in cancer patients. A systematic review of the available literature was conducted. The body

  8. Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients.

    NARCIS (Netherlands)

    Saunders, D.P.; Epstein, J.B.; Elad, S.; Allemano, J.; Bossi, P.; Wetering, M.D. van de; Rao, N.G.; Potting, C.M.J.; Cheng, K.K.; Freidank, A.; Brennan, M.T.; Bowen, J.; Dennis, K.; Lalla, R.V.

    2013-01-01

    PURPOSE: The aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis (OM) in cancer patients. METHODS: A systematic review of the available literature was

  9. CT findings of colonic diverticulitis

    International Nuclear Information System (INIS)

    Sasaki, Shigeru; Ohba, Satoru; Mizutani, Masaru

    1998-01-01

    Although colonic diverticulitis has no indication for operation, but in some mistaken cases were operated with a diagnosis of acute appendicitis. We evaluated the CT findings of colonic diverticulitis about 19 cases and of asymptomatic colonic diverticula about 15 cases retrospectively. Diagnosis was confirmed of barium enema and operation. CT are complementary methods of examination that can delineated the range of thickening of the colon and the extension of inflammatory changes around the colon. We also believe that CT findings of colonic diverticulitis are useful for differentiating from a diagnosis of appendicitis. (author)

  10. Mucosal biofilm detection in chronic otitis media

    DEFF Research Database (Denmark)

    Wessman, Marcus; Bjarnsholt, Thomas; Eickhardt-Sørensen, Steffen Robert

    2015-01-01

    The objectives of this study were to examine middle ear biopsies from Greenlandic patients with chronic otitis media (COM) for the presence of mucosal biofilms and the bacteria within the biofilms. Thirty-five middle ear biopsies were obtained from 32 Greenlandic COM patients admitted to ear...... of the patients served as controls. PNA-FISH showed morphological signs of biofilms in 15 out of 35 (43 %) middle ear biopsies. In the control skin biopsies, there were signs of biofilms in eight out of 23 biopsies (30 %), probably representing skin flora. PCR and 16s sequencing detected bacteria in seven out...... of 20 (35 %) usable middle ear biopsies, and in two out of ten (20 %) usable control samples. There was no association between biofilm findings and PCR and 16s sequencing. Staphylococci were the most common bacteria in bacterial culture. We found evidence of bacterial biofilms in 43 % of middle ear...

  11. Mucosal immunity to pathogenic intestinal bacteria.

    Science.gov (United States)

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

    2016-03-01

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

  12. Colonic potassium handling

    DEFF Research Database (Denmark)

    Sørensen, Mads Vaarby; Matos, Joana E.; Prætorius, Helle

    2010-01-01

    , intestinal K+ losses caused by activated ion secretion may become life threatening. This topical review provides an update of the molecular mechanisms and the regulation of mammalian colonic K+ absorption and secretion. It is motivated by recent results, which have identified the K+ secretory ion channel...... regulated by hormones and adapts readily to changes in dietary K+ intake, aldosterone and multiple local paracrine agonists. In chronic renal insufficiency, colonic K+ secretion is greatly enhanced and becomes an important accessory K+ excretory pathway. During severe diarrheal diseases of different causes...

  13. Use of prototype two-channel endoscope with elevator enables larger lift-and-snare endoscopic mucosal resection in a porcine model.

    Science.gov (United States)

    Atkinson, Matthew; Chukwumah, Chike; Marks, Jeffrey; Chak, Amitabh

    2014-02-01

    Flat and depressed lesions are becoming increasingly recognized in the esophagus, stomach, and colon. Various techniques have been described for endoscopic mucosal resection (EMR) of these lesions. To evaluate the efficacy of lift-grasp-cut EMR using a prototype dual-channel forward-viewing endoscope with an instrument elevator in one accessory channel (dual-channel elevator scope) as compared to standard dual-channel endoscopes. EMR was performed using a lift-grasp-cut technique on normal flat rectosigmoid or gastric mucosa in live porcine models after submucosal injection of 4 mL of saline using a dual-channel elevator scope or a standard dual-channel endoscope. With the dual-channel elevator scope, the elevator was used to attain further lifting of the mucosa. The primary endpoint was size of the EMR specimen and the secondary endpoint was number of complications. Twelve experiments were performed (six gastric and six colonic). Mean specimen diameter was 2.27 cm with the dual-channel elevator scope and 1.34 cm with the dual-channel endoscope (P = 0.018). Two colonic perforations occurred with the dual-channel endoscope, vs no complications with the dual-channel elevator scope. The increased lift of the mucosal epithelium, through use of the dual-channel elevator scope, allows for larger EMR when using a lift-grasp-cut technique. Noting the thin nature of the porcine colonic wall, use of the elevator may also make this technique safer.

  14. Circular mucosal anopexy: Experience and technical considerations.

    Science.gov (United States)

    Hidalgo Grau, Luis Antonio; Ruiz Edo, Neus; Llorca Cardeñosa, Sara; Heredia Budó, Adolfo; Estrada Ferrer, Óscar; Del Bas Rubia, Marta; García Torralbo, Eva María; Suñol Sala, Xavier

    2016-05-01

    Circular mucosal anopexy (CMA) achieves a more comfortable postoperative period than resective techniques. But complications and recurrences are not infrequent. This study aims to evaluate of the efficacy of CMA in the treatment of hemorrhoids and rectal mucosal prolapse (RMP). From 1999 to 2011, 613 patients underwent surgery for either hemorrhoids or RMP in our hospital. CMA was performed in 327 patients. Gender distribution was 196 male and 131 female. Hemorrhoidal grades were distributed as follows: 28 patients had RMP, 46 2nd grade, 146 3rd grade and 107 4th grade. Major ambulatory surgery (MAS) was performed in 79.9%. Recurrence of hemorrhoids was studied and groups of recurrence and no-recurrence were compared. Postoperative pain was evaluated by Visual Analogical Scale (VAS) as well as early complications. A total of 31 patients needed reoperation (5 RMP, 2 with 2nd grade, 17 with 3rd grade,/with 4th grade). No statistically significant differences were found between the non-recurrent group and the recurrent group with regards to gender, surgical time or hemorrhoidal grade, but there were differences related to age. In the VAS, 81.3% of patients expressed a postoperative pain ≤ 2 at the first week. Five patients needed reoperation for early postoperative bleeding. Six patients needed admission for postoperative pain. Recurrence rate is higher in CMA than in resective techniques. CMA is a useful technique for the treatment of hemorrhoids in MAS. Pain and the rate of complications are both low. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Sex hormones and mucosal wound healing.

    Science.gov (United States)

    Engeland, Christopher G; Sabzehei, Bahareh; Marucha, Phillip T

    2009-07-01

    Wound healing studies, which have chiefly examined dermal tissues, have reported a female advantage in healing rates. In contrast, our laboratory recently demonstrated women heal mucosal wounds more slowly than men. We hypothesized sex hormones influence wound healing rates, possibly through their modulating effects on inflammation. This study involved 329 younger subjects aged 18-43 (165 women, 164 men) and 93 older subjects aged 50-88 (60 women, 33 men). A 3.5mm diameter wound was created on the hard oral palate and videographed daily to assess wound closure. Blood collected at the time of wounding was used to assess circulating testosterone, progesterone and estradiol levels, and in vitro cytokine production in response to LPS. No strong associations were observed between healing times and estradiol or progesterone levels. However, in younger subjects, lower testosterone levels related to faster wound closure. Conversely, in older women higher testosterone levels related to (1) lower inflammatory responses; and (2) faster healing times. No such relationships were seen in older men, or in women taking oral contraceptives or hormone replacement therapy [HRT]. Older women (50-54 years) not yet experiencing menopause healed similarly to younger women and dissimilarly from age-matched post-menopausal women. This suggests that the deleterious effects of aging on wound healing occur secondary to the effects of menopause. Supporting this, there was evidence in post-menopausal women that HRT augmented wound closure. Overall, this study suggests that human mucosal healing rates are modulated by testosterone levels. Based upon when between-group differences were observed, testosterone may impact upon the proliferative phase of healing which involves immune processes such as re-epithelialization and angiogenesis.

  16. Colon Necrosis Due to Sodium Polystyrene Sulfonate with and without Sorbitol: An Experimental Study in Rats.

    Science.gov (United States)

    Ayoub, Isabelle; Oh, Man S; Gupta, Raavi; McFarlane, Michael; Babinska, Anna; Salifu, Moro O

    2015-01-01

    Based on a single rat study by Lillemoe et al, the consensus has been formed to implicate sorbitol rather than sodium polystyrene sulfonate (SPS) as the culprit for colon necrosis in humans treated with SPS and sorbitol. We tested the hypothesis that colon necrosis by sorbitol in the experiment was due to the high osmolality and volume of sorbitol rather than its chemical nature. 26 rats underwent 5/6 nephrectomy. They were divided into 6 groups and given enema solutions under anesthesia (normal saline, 33% sorbitol, 33% mannitol, SPS in 33% sorbitol, SPS in normal saline, and SPS in distilled water). They were sacrificed after 48 hours of enema administration or earlier if they were very sick. The gross appearance of the colon was visually inspected, and then sliced colon tissues were examined under light microscopy. 1 rat from the sorbitol and 1 from the mannitol group had foci of ischemic colonic changes. The rats receiving SPS enema, in sorbitol, normal saline, distilled water, had crystal deposition with colonic necrosis and mucosal erosion. All the rats not given SPS survived until sacrificed at 48 h whereas 11 of 13 rats that received SPS in sorbitol, normal saline or distilled water died or were clearly dying and sacrificed sooner. There was no difference between sorbitol and mannitol when given without SPS. In a surgical uremic rat model, SPS enema given alone or with sorbitol or mannitol seemed to cause colon necrosis and high mortality rate, whereas 33% sorbitol without SPS did not.

  17. Mucosal pathobiology and molecular signature of epithelial barrier dysfunction in the small intestine in irritable bowel syndrome.

    Science.gov (United States)

    González-Castro, Ana M; Martínez, Cristina; Salvo-Romero, Eloísa; Fortea, Marina; Pardo-Camacho, Cristina; Pérez-Berezo, Teresa; Alonso-Cotoner, Carmen; Santos, Javier; Vicario, María

    2017-01-01

    Irritable bowel syndrome (IBS) is one of the most prevalent gastrointestinal disorders in developed countries. Its etiology remains unknown; however, a common finding, regardless of IBS subtype, is the presence of altered intestinal barrier. In fact, signaling and location of cell-to-cell adhesion proteins, in connection with increased immune activity, seem abnormal in the intestinal epithelium of IBS patients. Despite that most research is performed on distal segments of the intestine, altered permeability has been reported in both, the small and the large bowel of all IBS subtypes. The small intestine carries out digestion and nutrient absorption and is also the site where the majority of immune responses to luminal antigens takes place. In fact, the upper intestine is more exposed to environmental antigens than the colon and is also a site of symptom generation. Recent studies have revealed small intestinal structural alterations of the epithelial barrier and mucosal immune activation in association with intestinal dysfunction, suggesting the commitment of the intestine as a whole in the pathogenesis of IBS. This review summarizes the most recent findings on mucosal barrier alterations and its relationship to symptoms arising from the small intestine in IBS, including epithelial structural abnormalities, mucosal immune activation, and microbial dysbiosis, further supporting the hypothesis of an organic origin of IBS. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  18. Allopurinol gel mitigates radiation-induced mucositis and dermatitis

    International Nuclear Information System (INIS)

    Kitagawa, Junichi; Nasu, Masanori; Okumura, Hayato; Matsumoto, Shigeji; Shibata, Akihiko; Makino, Kimiko; Terada, Hiroshi

    2008-01-01

    It has not been verified whether allopurinol application is beneficial in decreasing the severity of radiation-induced oral mucositis and dermatitis. Rats were divided into 4 groups and received 15 Gy irradiation on the left whisker pad. Group 1 received only irradiation. Group 2 was maintained by applying allopurinol/carrageenan-mixed gel (allopurinol gel) continuously from 2 days before to 20 days after irradiation. Group 3 had allopurinol gel applied for 20 days after radiation. Group 4 was maintained by applying carrageenan gel continuously from 2 days before to 20 days after irradiation. The intra oral mucosal and acute skin reactions were assessed daily using mucositis and skin score systems. The escape thresholds for mechanical stimulation to the left whisker pad were measured daily. In addition, the irradiated tissues at the endpoint of this study were compared with naive tissue. Escape threshold in group 2 was significantly higher than that in group 1, and mucositis and skin scores were much improved compared with those of group 1. Concerning escape threshold, mucositis and skin scores in group 3 began to improve 10 days after irradiation. Group 4 showed severe symptoms of mucositis and dermatitis to the same extent as that observed in group 1. In the histopathological study, the tissues of group 1 showed severe inflammatory reactions, compared with those of group 2. These results suggest that allopurinol gel application can mitigate inflammation reactions associated with radiation-induced oral mucositis and dermatitis. (author)

  19. Sucralfate for the treatment of radiation induced mucositis

    International Nuclear Information System (INIS)

    Belka, C.; Hoffmann, W.; Paulsen, F.; Bamberg, M.

    1997-01-01

    Purpose: Radiotherapy, a cornerstone in the management of head and neck cancer, pelvic cancer, and esophageal cancer is associated with a marked mucosal toxicity. Pain, malnutrition and diarrhea are the most prevalent clinical symptoms of radiation induced mucosal damage. Because there is no known way to obviate radiation mucositis all efforts to prevent aggravation and accelerate healing of mucosal changes are of great importance. Numerous agents including antimicrobials, local and systemic analgesics, antiinflammatory drugs, antidiarrheal drugs, in combination with intensive dietetic care are used to relieve symptoms. Recently coating agents like the polyaluminum-sucrose complex sucralfate were suggested for the prevention and treatment of mucosal reactions. Since sucralfate protects ulcerated epithelium by coating, liberates protective prostaglandins and increases the local availability of protective factors this drug might directly interact with the pathogenesis of mucositis. Patients and Method: The results of available studies are analysed and discussed. Results: The results of several studies indicate that sucralfate treatment especially during radiotherapy for pelvic cancer leads to a significant amelioration of clinical symptoms and morphological changes. An application of sucralfate during radiotherapy of head and neck cancer reveals only limited benefits in most studies performed. Conclusion: Nevertheless sucralfate is a save, cheap and active drug for the prevention and treatment of radiation mucositis especially in patients with pelvic irradiation. (orig.) [de

  20. Roles of Mucosal Immunity against Mycobacterium tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Wu Li

    2012-01-01

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

  1. Surgical outcome in headache due to mucosal contact

    International Nuclear Information System (INIS)

    Goto, Fumiyuki; Yabe, Haruna; Ogawa, Kaoru

    2010-01-01

    Headaches is classified as primary and secondary, with secondary originating in head and neck conditions, the most important etiology being acute sinusitis. Headache due to mucosal contact, rarely encountered by otorhinolaryngologists, is an important secondary headache, whose criteria are defined by the International Classification of Headache Disorders to include intermittent pain localized in the periorbital and medial canthal or temporozygomatic regions, evidence that pain is attributable to mucosal contact and the presence of mucosal contact in the absence of acute rhinosinusitis, obtained using clinical examinations, nasal endoscopy, and/or computed tomography (CT). After mucosal contact is surgically corrected pain usually disappears permanently within 7 days. We reviewed mucosal contact headaches in 63 subjects undergoing nasal or paranasal surgery from April 2007 to March 2008. Of those 7 were diagnosed with headaches due to contact points in nasal mucosa, ranging from canthal to the temporozygomatic. The most common contact, between the middle turbinate and nasal septum, was seen in 6 of the 7. Surgery eliminated symptoms in 4 and ameliorated them in 3 indicating effective headache management. Subjects with severe headaches or localized periorbital and medial canthal pain regions, mucosal contact involvement is ruled out when CT allows no lesions. When mucosal contact headache is suspected, however surgery should be considered as a last resort. (author)

  2. Stimulation of mucosal immune response following oral administration of enterotoxigenic Escherichia coli fimbriae (CFA/I) entrapped in liposomes in conjunction with inactivated whole-cell Vibrio cholerae vaccine.

    Science.gov (United States)

    Dima, V F; Ionescu, M D; Palade, R; Balotescu, C; Becheanu, G; Dima, S V

    2001-01-01

    In this study, we have searched for an effective mucosal vaccine. An oral enterotoxigenic E. coli vaccine containing colonization factor antigen (CFA/I) associated with inactivated whole-cell V. cholerae vaccine (WCV) has been tested for safety and immunogenicity in animals. Five groups of animals were used. The results showed the following: (a) vaccine containing CFA/I antigen entrapped in liposomes and associated with WCV (batch C) had increased titers of specific antibodies to CFA/I antigen in 15 to 18 (83.3%) animals; (b) specific Peyer's patches (PP), lymph nodes (LN) and spleen (SPL) lymphocytes proliferation was detected following in vitro restimulation with CFA/I antigen or WCV. This response gradually increased to the highest value by the 35th postimmunization day. Moreover, lower PP, LN and spleen (SPL) proliferation was observed in rabbits receiving soluble CFA/I antigen (S-CFA/I) or free liposomes (F-L) alone; (c) adhesion of E. coli H10407 strain labelled with 3H-leucine in immunized and control animals revealed the following local effects: (i) protection of rabbit intestinal mucosa against virulent E. coli cells; (ii) inhibition of adhesion of ETEC bacteria to intestinal mucosa and (iii) significantly faster release of E. coli H 10407 strain labelled with 3H-leucine from the intestinal tract of immunized animals. The histopathological and electron microscope findings confirmed the above results. The experimental results point out an efficient protection against infection with E. coli strains (ETEC), after mucosal vaccination with CFA/I antigen entrapped in liposomes associated with inactivated whole-cell Vibrio cholerae as immunological adjuvant.

  3. Colonization, mouse-style

    Directory of Open Access Journals (Sweden)

    Searle Jeremy B

    2010-10-01

    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

  4. Calcitonin Gene-Related Peptide Induces HIV-1 Proteasomal Degradation in Mucosal Langerhans Cells.

    Science.gov (United States)

    Bomsel, Morgane; Ganor, Yonatan

    2017-12-01

    The neuroimmune dialogue between peripheral neurons and Langerhans cells (LCs) within mucosal epithelia protects against incoming pathogens. LCs rapidly internalize human immunodeficiency virus type 1 (HIV-1) upon its sexual transmission and then trans -infect CD4 + T cells. We recently found that the neuropeptide calcitonin gene-related peptide (CGRP), secreted mucosally from peripheral neurons, inhibits LC-mediated HIV-1 trans -infection. In this study, we investigated the mechanism of CGRP-induced inhibition, focusing on HIV-1 degradation in LCs and its interplay with trans -infection. We first show that HIV-1 degradation occurs in endolysosomes in untreated LCs, and functionally blocking such degradation with lysosomotropic agents results in increased trans -infection. We demonstrate that CGRP acts via its cognate receptor and at a viral postentry step to induce faster HIV-1 degradation, but without affecting the kinetics of endolysosomal degradation. We reveal that unexpectedly, CGRP shifts HIV-1 degradation from endolysosomes toward the proteasome, providing the first evidence for functional HIV-1 proteasomal degradation in LCs. Such efficient proteasomal degradation significantly inhibits the first phase of trans -infection, and proteasomal, but not endolysosomal, inhibitors abrogate CGRP-induced inhibition. Together, our results establish that CGRP controls the HIV-1 degradation mode in LCs. The presence of endogenous CGRP within innervated mucosal tissues, especially during the sexual response, to which CGRP contributes, suggests that HIV-1 proteasomal degradation predominates in vivo Hence, proteasomal, rather than endolysosomal, HIV-1 degradation in LCs should be enhanced clinically to effectively restrict HIV-1 trans -infection. IMPORTANCE During sexual transmission, HIV-1 is internalized and degraded in LCs, the resident antigen-presenting cells in mucosal epithelia. Yet during trans -infection, infectious virions escaping degradation are transferred

  5. Possible association of mucous blanket integrity with postirradiation colonization resistance

    International Nuclear Information System (INIS)

    Walker, R.I.; Brook, I.; Costerton, J.W.; MacVittie, T.; Myhal, M.L.

    1985-01-01

    Radiation-induced infections can be associated with changes in colonization potential of the intestine. Since the mucous blanket, which overlays the epithelium, is a major mucosal structure and is heavily colonized by microorganisms, we examined the status of the mucus after radiation and evaluated susceptibility to intestinal challenge with bacteria. A downward shift (2.5 X 10(8) cells/g to 5.3 X 10(5)) of total facultatively anaerobic bacteria of the ileum of C3HeB/FeJ mice was detected by 3 days post exposure to 10 Gy 60Co. Numbers of flora returned to normal by 11 days after radiation. Scanning electron microscopy was used to show that the loss of bacteria could be associated with major disruptions of the continuity of the mucous blanket. The pathogen Pseudomonas aeruginosa adhered to mouse mucous films used in in vitro assays. When irradiated mice were challenged orally with 1 X 10(5) P. aeruginosa on days 1, 2, or 3 after irradiation, a progressive increase in susceptibility was seen, but no animals died before Day 4 postirradiation. Sensitivity to subcutaneous (sc) challenge with Pseudomonas also increased by Day 3 and was probably due largely to the profound neutropenia observed. Immunoglobulin G (Gamimmune), which protected burned mice infected with Pseudomonas, was ineffectual in treatment of 7 or 10 Gy irradiated mice challenged either orally or sc with the organism. The ileal mucosal barrier was compromised after radiation in ways which could facilitate epithelial colonization, an event which combined with other immunological and physiological decrements in this model can compromise the effectiveness of therapeutic modalities

  6. Schwannoma of the Colon

    Directory of Open Access Journals (Sweden)

    Ronaldo Nonose

    2009-09-01

    Full Text Available Schwannomas are neoplasms originating from Schwann cells, which are the cells forming nerve sheaths. These neoplasms generally involve peripheral nerves. They rarely affect the gastrointestinal tract and primary colon involvement is extremely rare. The objective of the present paper was to present a case of primary schwannoma of the sigmoid colon, unassociated with von Recklinghausen disease, that was histopathologically confirmed by means of an immunohistochemical panel. The patient was a 71-year-old woman who had had rectal bleeding when evacuating, with pain and tenesmus, for 4 months. She underwent colonoscopy, which identified a raised submucous lesion of 2.8 cm in diameter, located in the sigmoid colon, 30 cm from the anal margin. During examination, loop polypectomy with lesion excision was performed. Histopathological evaluation showed that this was a tumor of stromal origin. Its resection margins were compromised by neoplasia, and colon resection by means of videolaparoscopy was indicated. Conventional histopathological examination using the hematoxylin-eosin technique suggested that the neoplasm was of mesenchymal origin. An immunohistochemical panel was run for etiological confirmation, using anti-CD34 antibodies, desmin, cytokeratins (AE1/AE3, cKit, chromogranin and S-100 protein. The panel showed intense immunoexpression of S-100 protein. Investigation of the proliferative activity rate using Ki-67 antibodies showed that there was a low rate of mitotic activity, thus confirming the diagnosis of primary benign schwannoma of the colon. The patient’s postoperative evolution was uneventful and she remains in good health, without signs of tumor recurrence, 15 months after surgical excision.

  7. External coating of colonic anastomoses

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Achiam, Michael Patrick; Rosenberg, Jacob

    2012-01-01

    Colon anastomotic leakage remains both a frequent and serious complication in gastrointestinal surgery. External coating of colonic anastomoses has been proposed as a means to lower the rate of this complication. The aim of this review was to evaluate existing studies on external coating of colonic...

  8. Endoscopic biopsies in Ussing chambers evaluated for studies of macromolecular permeability in the human colon.

    Science.gov (United States)

    Wallon, Conny; Braaf, Ylva; Wolving, Mats; Olaison, Gunnar; Söderholm, Johan D

    2005-05-01

    Studies of mucosal permeability to protein antigens in humans are limited to in vitro techniques. The use of surgical specimens for such studies has major shortcomings. Endoscopic biopsies in Ussing chambers have been introduced as a means of studying secretion and transepithelial permeability, but have not been evaluated for studies of protein antigen uptake in human intestine. Standard forceps biopsies from the sigmoid colon of 24 healthy volunteers were mounted in Ussing chambers with an exposed tissue area of 1.76 mm2. 51Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP; 45 kDa protein antigen) were used as permeability markers. Mucosal permeability, electrophysiology, histology and energy contents of the biopsies were studied over time. To evaluate the ability of the technique to detect permeability changes, the mucosa was modulated with capric acid, a medium-chain fatty acid, known to affect tight junctions. In the Ussing chamber the mucosal biopsies were viable for 160 min with stable levels of ATP and lactate, and only minor changes in morphology. Steady-state permeability with low variability was seen for both markers during the 30-90 min period. Exposure to capric acid induced a rapid decrease in short-circuit current (Isc) and a slower reversible decrease in transepithelial resistance (TER), as well as an increased permeability to 51Cr-EDTA and HRP. Endoscopic biopsies of human colon are viable in Ussing chambers and are reliable tools for studies of mucosal permeability to protein antigens. The technique offers a broad potential for studies of mucosal function in the pathophysiology of human gastrointestinal diseases.

  9. Secretion of biologically active pancreatitis-associated protein I (PAP) by genetically modified dairy Lactococcus lactis NZ9000 in the prevention of intestinal mucositis.

    Science.gov (United States)

    Carvalho, Rodrigo D; Breyner, Natalia; Menezes-Garcia, Zelia; Rodrigues, Nubia M; Lemos, Luisa; Maioli, Tatiane U; da Gloria Souza, Danielle; Carmona, Denise; de Faria, Ana M C; Langella, Philippe; Chatel, Jean-Marc; Bermúdez-Humarán, Luis G; Figueiredo, Henrique C P; Azevedo, Vasco; de Azevedo, Marcela S

    2017-02-13

    Mucositis is one of the most relevant gastrointestinal inflammatory conditions in humans, generated by the use of chemotherapy drugs, such as 5-fluoracil (5-FU). 5-FU-induced mucositis affects 80% of patients undergoing oncological treatment causing mucosal gut dysfunctions and great discomfort. As current therapy drugs presents limitations in alleviating mucositis symptoms, alternative strategies are being pursued. Recent studies have shown that the antimicrobial pancreatitis-associated protein (PAP) has a protective role in intestinal inflammatory processes. Indeed, it was demonstrated that a recombinant strain of Lactococcus lactis expressing human PAP (LL-PAP) could prevent and improve murine DNBS-induced colitis, an inflammatory bowel disease (IBD) that causes severe inflammation of the colon. Hence, in this study we sought to evaluate the protective effects of LL-PAP on 5-FU-induced experimental mucositis in BALB/c mice as a novel approach to treat the disease. Our results show that non-recombinant L. lactis NZ9000 have antagonistic activity, in vitro, against the enteroinvasive gastrointestinal pathogen L. monocytogenes and confirmed PAP inhibitory effect against Opportunistic E. faecalis. Moreover, L. lactis was able to prevent histological damage, reduce neutrophil and eosinophil infiltration and secretory Immunoglobulin-A in mice injected with 5-FU. Recombinant lactococci carrying antimicrobial PAP did not improve those markers of inflammation, although its expression was associated with villous architecture preservation and increased secretory granules density inside Paneth cells in response to 5-FU inflammation. We have demonstrated for the first time that L. lactis NZ9000 by itself, is able to prevent 5-FU-induced intestinal inflammation in BALB/c mice. Moreover, PAP delivered by recombinant L. lactis strain showed additional protective effects in mice epithelium, revealing to be a promising strategy to treat intestinal mucositis.

  10. Prior mucosal exposure to heterologous cells alters the pathogenesis of cell-associated mucosal feline immunodeficiency virus challenge

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    Leavell Sarah

    2010-05-01

    Full Text Available Abstract Background Several lines of research suggest that exposure to cellular material can alter the susceptibility to infection by HIV-1. Because sexual contact often includes exposure to cellular material, we hypothesized that repeated mucosal exposure to heterologous cells would induce an immune response that would alter the susceptibility to mucosal infection. Using the feline immunodeficiency virus (FIV model of HIV-1 mucosal transmission, the cervicovaginal mucosa was exposed once weekly for 12 weeks to 5,000 heterologous cells or media (control and then cats were vaginally challenged with cell-associated or cell-free FIV. Results Exposure to heterologous cells decreased the percentage of lymphocytes in the mucosal and systemic lymph nodes (LN expressing L-selectin as well as the percentage of CD4+ CD25+ T cells. These shifts were associated with enhanced ex-vivo proliferative responses to heterologous cells. Following mucosal challenge with cell-associated, but not cell-free, FIV, proviral burden was reduced by 64% in cats previously exposed to heterologous cells as compared to media exposed controls. Conclusions The pathogenesis and/or the threshold for mucosal infection by infected cells (but not cell-free virus can be modulated by mucosal exposure to uninfected heterologous cells.

  11. Multiplex immunoassay of lower genital tract mucosal fluid from women attending an urban STD clinic shows broadly increased IL1ß and lactoferrin.

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    Gregory T Spear

    Full Text Available BACKGROUND: More than one million new cases of sexually transmitted diseases (STDs occur each day. The immune responses and inflammation induced by STDs and other frequent non-STD microbial colonizations (i.e. Candida and bacterial vaginosis can have serious pathologic consequences in women including adverse pregnancy outcomes, infertility and increased susceptibility to infection by other pathogens. Understanding the types of immune mediators that are elicited in the lower genital tract by these infections/colonizations can give important insights into the innate and adaptive immune pathways that are activated and lead to strategies for preventing pathologic effects. METHODOLOGY/PRINCIPAL FINDINGS: 32 immune mediators were measured by multiplexed immunoassays to assess the immune environment of the lower genital tract mucosa in 84 women attending an urban STD clinic. IL-3, IL-1ß, VEGF, angiogenin, IL-8, ß2Defensin and ß3Defensin were detected in all subjects, Interferon-α was detected in none, while the remaining mediators were detected in 40% to 93% of subjects. Angiogenin, VEGF, FGF, IL-9, IL-7, lymphotoxin-α and IL-3 had not been previously reported in genital mucosal fluid from women. Strong correlations were observed between levels of TNF-α, IL-1ß and IL-6, between chemokines IP-10 and MIG and between myeloperoxidase, IL-8 and G-CSF. Samples from women with any STD/colonization had significantly higher levels of IL-8, IL-3, IL-7, IL-1ß, lactoferrin and myeloperoxidase. IL-1ß and lactoferrin were significantly increased in gonorrhea, Chlamydia, cervicitis, bacterial vaginosis and trichomoniasis. CONCLUSIONS/SIGNIFICANCE: These studies show that mucosal fluid in general appears to be an environment that is rich in immune mediators. Importantly, IL-1ß and lactoferrin are biomarkers for STDs/colonizations providing insights into immune responses and pathogenesis at this mucosal site.

  12. Challenges in the local delivery of peptides and proteins for oral mucositis management.

    Science.gov (United States)

    Campos, João C; Cunha, João D; Ferreira, Domingos C; Reis, Salette; Costa, Paulo J

    2018-04-24

    Oral mucositis, a common inflammatory side effect of oncological treatments, is a disorder of the oral mucosa that can cause painful ulcerations, local motor disabilities, and an increased risk of infections. Due to the discomfort it produces and the associated health risks, it can lead to cancer treatment restrains, such as the need for dose reduction, cycle delays or abandonment. Current mucositis management has low efficiency in prevention and treatment. A topical drug application for a local action can be a more effective approach than systemic routes when addressing oral cavity pathologies. Local delivery of growth factors, antibodies, and anti-inflammatory cytokines have shown promising results. However, due to the peptide and protein nature of these novel agents, and the several anatomic, physiological and environmental challenges of the oral cavity, their local action might be limited when using traditional delivering systems. This review is an awareness of the issues and strategies in the local delivery of macromolecules for the management of oral mucositis. Copyright © 2018. Published by Elsevier B.V.

  13. Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells.

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    Jason A Neidleman

    2017-02-01

    Full Text Available Understanding early events of HIV transmission within mucosal tissues is vital for developing effective prevention strategies. Here, we report that primary stromal fibroblasts isolated from endometrium, cervix, foreskin, male urethra, and intestines significantly increase HIV infection of CD4+ T cells-by up to 37-fold for R5-tropic HIV and 100-fold for X4-tropic HIV-without themselves becoming infected. Fibroblasts were more efficient than dendritic cells at trans-infection and mediate this response in the absence of the DC-SIGN and Siglec-1 receptors. In comparison, mucosal epithelial cells secrete antivirals and inhibit HIV infection. These data suggest that breaches in the epithelium allow external or luminal HIV to escape an antiviral environment to access the infection-favorable environment of the stromal fibroblasts, and suggest that resident fibroblasts have a central, but previously unrecognized, role in HIV acquisition at mucosal sites. Inhibiting fibroblast-mediated enhancement of HIV infection should be considered as a novel prevention strategy.

  14. Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections

    Science.gov (United States)

    Chentoufi, Aziz Alami; BenMohamed, Lbachir

    2012-01-01

    Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) are amongst the most common human infectious viral pathogens capable of causing serious clinical diseases at every stage of life, from fatal disseminated disease in newborns to cold sores genital ulcerations and blinding eye disease. Primary mucocutaneous infection with HSV-1 & HSV-2 is followed by a lifelong viral latency in the sensory ganglia. In the majority of cases, herpes infections are clinically asymptomatic. However, in symptomatic individuals, the latent HSV can spontaneously and frequently reactivate, reinfecting the muco-cutaneous surfaces and causing painful recurrent diseases. The innate and adaptive mucosal immunities to herpes infections and disease remain to be fully characterized. The understanding of innate and adaptive immune mechanisms operating at muco-cutaneous surfaces is fundamental to the design of next-generation herpes vaccines. In this paper, the phenotypic and functional properties of innate and adaptive mucosal immune cells, their role in antiherpes immunity, and immunopathology are reviewed. The progress and limitations in developing a safe and efficient mucosal herpes vaccine are discussed. PMID:23320014

  15. Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections

    Directory of Open Access Journals (Sweden)

    Aziz Alami Chentoufi

    2012-01-01

    Full Text Available Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2 are amongst the most common human infectious viral pathogens capable of causing serious clinical diseases at every stage of life, from fatal disseminated disease in newborns to cold sores genital ulcerations and blinding eye disease. Primary mucocutaneous infection with HSV-1 & HSV-2 is followed by a lifelong viral latency in the sensory ganglia. In the majority of cases, herpes infections are clinically asymptomatic. However, in symptomatic individuals, the latent HSV can spontaneously and frequently reactivate, reinfecting the muco-cutaneous surfaces and causing painful recurrent diseases. The innate and adaptive mucosal immunities to herpes infections and disease remain to be fully characterized. The understanding of innate and adaptive immune mechanisms operating at muco-cutaneous surfaces is fundamental to the design of next-generation herpes vaccines. In this paper, the phenotypic and functional properties of innate and adaptive mucosal immune cells, their role in antiherpes immunity, and immunopathology are reviewed. The progress and limitations in developing a safe and efficient mucosal herpes vaccine are discussed.

  16. Dose-response studies of depletion and repopulation of rat intestinal mucosal mast cells after irradiation

    International Nuclear Information System (INIS)

    Sedgwick, D.M.; Ferguson, A.

    1994-01-01

    The effects of radiation on gut mucosal mast cells (MMC) and tissue eosinophils were examined. Groups of rats were given single doses of whole-body irradiation from 0.5 to 5 Gy. Serum rat mast cell protease II (RMCPII) concentration showed a significant dose-dependent fall after 1 Gy on day 3 and 1.5 Gy on day 7. MMC counts and tissue RMCPII values on day 7 decreased significantly by 70% after 1 Gy and were undetectable with larger doses. Rats with normal and expanded MMC populations were irradiated or given anaphylaxis. Serum RMCPII concentrations did not change after irradiation, but there was a 10-fold increase in RMCPII after anaphylaxis. Tissue eosinophils in jejunum were 50% of control at 7 days after 2 Gy, and this effect was progressively more marked with higher doses. Similar effects on MMC and eosinophils were demonstrated in ileum, ascending colon and rectum. After 4.5 Gy, repopulation of the gut with MMC did not occur until week 3-4 postirradiation and MMC counts were still 50% below those of controls at 5 weeks postirradiation. Counts of tisse eosinophils 5 weeks after 4.5 Gy irradiation had returned to control levels in jejunum but were still significantly depleted in colon. (Author)

  17. Inflammatory chronic disease of the colon: How to image

    International Nuclear Information System (INIS)

    Ambrosini, Roberta; Barchiesi, Annalisa; Di Mizio, Veronica; Di Terlizzi, Marco; Leo, Luca; Filippone, Antonella; Canalis, Luigi; Fossaceca, Rita; Carriero, Alessandro

    2007-01-01

    Inflammatory bowel disease, including Crohn's disease and UC, is a chronic disorder of the gastrointestinal tract. The inflammatory process in UC is confined to the mucosa and submucosa and it involves only the colon. In contrast, in Crohn's disease the inflammation process extends through the bowel wall layers and it can involve any part of gastrointestinal tract. Moreover, inflammatory bowel disease of the colon may be associated with complications, such as toxic megacolon, fulminant colitis, acute bleeding, fistulas and abscesses. Radiographic imaging studies are useful for the diagnosis of inflammatory bowel disease, and may be used to assess the extent and severity of disease, rule out complications, and monitor the response to therapy. The double-contrast barium study is a valuable technique for diagnosing inflammatory bowel disease colonic alterations, even in patients with early mucosal abnormalities. The earliest finding of UC is characterized by a fine granular appeareance of the colonic mucosa, usually involving the rectosigmoid junction. In chronic UC double-contrast enema may reveal marked colonic shortening with tubular narrowing of the bowel and loss of haustration. The earliest radiographics findings of Crohn's disease are represented by aphthous ulcers. As disease progresses, aphthous ulcers may enlarge and coalesce to form stellate or linear areas of ulceration. In advanced Crohn's disease, transmural ulceration may lead to the development of fissures, sinus tracts, fistulas, and abscesses. Cross sectional studies such as computed tomography, magnetic resonance imaging and sometimes ultrasound, are useful alternative tools not only in the assessment of bowel wall abnormalities, but also for the assessment of extraluminal alterations in patients with advanced disease

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

    Science.gov (United States)

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

  19. Vaginal agenesis: Experience with sigmoid colon neovaginoplasty

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    Rawat Jiledar

    2010-01-01

    Full Text Available Aim: Objective of this study is to report our experience with sigmoid vaginoplasty in adolescents. Materials and Methods: A retrospective study of children with vaginal atresia and Mayer-Rokitansky-Kuster-Hauser syndrome. The sigmoid segment was used for vaginoplasty in all the cases. Results: Eight children were studied over a period of 7 years. The postoperative complications were ileus in 2, mucosal prolapse of the neovagina in 1, and minor wound infection in 1 patient. Seven patients are on regular follow-up. All the neovaginas were patent and functional. One patient had unacceptable perineal appearance, that is, badly scarred perineum as a late complication. None of the patients had vaginal stenosis or excessive mucus discharge, during follow-up visits. Out of the 7 patients, 2 patients are sexually active and satisfied. Conclusions: Sigmoid vaginoplasty is a safe and acceptable procedure for vaginal agenesis with good cosmetic results and acceptable complications rate. Sigmoid colon vaginoplasty is the treatment of choice because of its large lumen, thick walls resistant to trauma, adequate secretion allowing lubrication, not necessitating prolonged dilatation, and short recovery time.

  20. Colonic spirochetosis in animals and humans.

    Science.gov (United States)

    Smith, James L

    2005-07-01

    Colonic spirochetosis is a disease caused by the gram-negative bacteria Brachyspira aalborgi and Brachyspira pilosicoli. B. pilosicoli induces disease in both humans and animals, whereas B. aalborgi affects only humans and higher primates. Symptoms in humans include diarrhea, rectal bleeding, and abdominal cramps. Colonic spirochetosis is common in third world countries; however, in developed countries, the disease is observed mainly in homosexual males. Terminally ill patients infected with Brachyspira are particularly at risk for developing spirochetemia. Diarrhea, poor growth performance, and decreased feed-to-gain efficiency is seen in pigs with colonic spirochetosis. The disease in chickens is characterized by delayed and/or reduced egg production, diarrhea, poor feed conversion, and retarded growth. Thus, colonic spirochetosis can represent a serious economic loss in the swine and poultry industries. The organisms are transmitted by the fecal-oral route, and several studies have demonstrated that human, primate, pig, dog, or bird strains of B. pilosicoli can be transmitted to pigs, chickens, and mice. B. pilosicoli may be a zoonotic pathogen, and although it has not been demonstrated, there is a possibility that both B. pilosicoli and B. aalborgi can be transferred to humans via contact with the feces of infected animals, meat from infected animals, or food contaminated by food handlers. Neither B. pilosicoli nor B. aalborgi has been well characterized in terms of basic cellular functions, pathogenicity, or genetics. Studies are needed to more thoroughly understand these Brachyspira species and their disease mechanisms.

  1. Uncommon mucosal metastases to the stomach

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    Kanthan R

    2009-08-01

    Full Text Available Abstract Background Metastases to the stomach from an extra-gastric neoplasm are an unusual event, identified in less than 2% of cancer patients at autopsy. The stomach may be involved by hematogenous spread from a distant primary (most commonly breast, melanoma or lung, or by contiguous spread from an adjacent malignancy, such as the pancreas, esophagus and gallbladder. These latter sites may also involve the stomach via lymphatic or haematogenous spread. We present three cases of secondary gastric malignancy. Methods/Results The first is a 19-year-old male who received a diagnosis of testicular choriocarcinoma in September 2004. Metastatic malignancy was demonstrated in the stomach after partial gastrectomy was performed to control gastric hemorrhage. The second is a 75-year-old male, generally well, who was diagnosed with adenocarcinoma of the lung in September 2005. Poorly differentiated adenocarcinoma of the lung was demonstrated in a subsequent biopsy of "gastric polyps". The third is an 85-year-old man with no known history of malignancy who presented for evaluation of iron deficiency anemia by endoscopy in February 2006. Biopsies of the colonic and gastric mucosa demonstrated moderately differentiated invasive colonic adenocarcinoma with metastatic deposits in the stomach. Conclusion While the accurate recognition of these lesions at endoscopy is fraught with difficulty, pathological awareness of such uncommon metastases in the gastric mucosa is essential for accurate diagnosis and optimal patient management.

  2. Vaccination against Salmonella Infection: the Mucosal Way.

    Science.gov (United States)

    Gayet, Rémi; Bioley, Gilles; Rochereau, Nicolas; Paul, Stéphane; Corthésy, Blaise

    2017-09-01

    Salmonella enterica subspecies enterica includes several serovars infecting both humans and other animals and leading to typhoid fever or gastroenteritis. The high prevalence of associated morbidity and mortality, together with an increased emergence of multidrug-resistant strains, is a current global health issue that has prompted the development of vaccination strategies that confer protection against most serovars. Currently available systemic vaccine approaches have major limitations, including a reduced effectiveness in young children and a lack of cross-protection among different strains. Having studied host-pathogen interactions, microbiologists and immunologists argue in favor of topical gastrointestinal administration for improvement in vaccine efficacy. Here, recent advances in this field are summarized, including mechanisms of bacterial uptake at the intestinal epithelium, the assessment of protective host immunity, and improved animal models that closely mimic infection in humans. The pros and cons of existing vaccines are presented, along with recent progress made with novel formulations. Finally, new candidate antigens and their relevance in the refined design of anti- Salmonella vaccines are discussed, along with antigen vectorization strategies such as nanoparticles or secretory immunoglobulins, with a focus on potentiating mucosal vaccine efficacy. Copyright © 2017 American Society for Microbiology.

  3. Mucosal effects of tenofovir 1% gel.

    Science.gov (United States)

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

    2015-02-03

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

  4. Cystic fibrosis: a mucosal immunodeficiency syndrome

    Science.gov (United States)

    Cohen, Taylor Sitarik; Prince, Alice

    2013-01-01

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

  5. [Recurrent pulmonary infection and oral mucosal ulcer].

    Science.gov (United States)

    Kuang, Fei-Mei; Tang, Lan-Lan; Zhang, Hui; Xie, Min; Yang, Ming-Hua; Yang, Liang-Chun; Yu, Yan; Cao, Li-Zhi

    2017-04-01

    An 8-year-old girl who had experienced intermittent cough and fever over a 3 year period, was admitted after experiencing a recurrence for one month. One year ago the patient experienced a recurrent oral mucosal ulcer. Physical examination showed vitiligo in the skin of the upper right back. Routine blood tests and immune function tests performed in other hospitals had shown normal results. Multiple lung CT scans showed pulmonary infection. The patient had recurrent fever and cough and persistent presence of some lesions after anti-infective therapy. The antitubercular therapy was ineffective. Routine blood tests after admission showed agranulocytosis. Gene detection was performed and she was diagnosed with dyskeratosis congenita caused by homozygous mutation in RTEL1. Patients with dyskeratosis congenita with RTEL1 gene mutation tend to develop pulmonary complications. Since RTEL1 gene sequence is highly variable with many mutation sites and patterns and can be inherited via autosomal dominant or recessive inheritance, this disease often has various clinical manifestations, which may lead to missed diagnosis or misdiagnosis. For children with unexplained recurrent pulmonary infection, examinations of the oral cavity, skin, and nails and toes should be taken and routine blood tests should be performed to exclude dyskeratosis congenita. There are no specific therapies for dyskeratosis congenita at present, and when bone marrow failure and pulmonary failure occur, hematopoietic stem cell transplantation and lung transplantation are the only therapies. Androgen and its derivatives are effective in some patients. Drugs targeting the telomere may be promising for patients with dyskeratosis congenita.

  6. Mucosal T cells in gut homeostasis and inflammation

    OpenAIRE

    van Wijk, Femke; Cheroutre, Hilde

    2010-01-01

    The antigen-rich environment of the gut interacts with a highly integrated and specialized mucosal immune system that has the challenging task of preventing invasion and the systemic spread of microbes, while avoiding excessive or unnecessary immune responses to innocuous antigens. Disruption of the mucosal barrier and/or defects in gut immune regulatory networks may lead to chronic intestinal inflammation as seen in inflammatory bowel disease. The T-cell populations of the intestine play a c...

  7. Mucosal Immune Regulation in Early Infancy: Monitoring and Intervention

    OpenAIRE

    Hol, Jeroen

    2011-01-01

    textabstractThe mucosal immune system of infants is dependent on the maintenance of mucosal homeostasis. Homeostasis results from the interaction between the mucosa and exogenous factors such as dietar and microbial agents. Induction and maintenance of homeostasis is a highly regluated system that involves different cell types. If homeostasis is lost this may lead to disease, including allergy and chronic intestinal inflammation. In this thesis we observed whether loss of homeostasis leading ...

  8. [Dietary prevention and treatment of diverticular disease of the colon].

    Science.gov (United States)

    Milewska, Magdalena; Sińska, Beata; Kluciński, Andrzej

    2015-04-01

    Diverticular disease is more often categorized as a civilization disease that affects both women and men, especially at an old age. The pathophysiology remains complex and arises from the interaction between dietary fiber intake, bowel motility and mucosal changes in the colon. Obesity, smoking, low physical activity, low-fiber diet (poor in vegetables, fruit, whole grain products, seeds and nuts) are among factors that increase the risk for developing diverticular disease. Additionally, the colonic outpouchings may be influenced by involutional changes of the gastrointestinal tract. Therefore, the fiber rich diet (25-40 g/day) plays an important role in prevention, as well as nonpharmacological treatment of uncomplicated diverticular disease. The successful goal of the therapy can be achieved by well-balanced diet or fiber supplements intake. Research indicate the effectiveness of probiotics in dietary management during the remission process. Moreover, drinking of appropriate water amount and excluding from the diet products decreasing colonic transit time - should be also applied. © 2015 MEDPRESS.

  9. Risk factors for fecal colonization with multiple distinct strains of Escherichia coli among long-term care facility residents.

    Science.gov (United States)

    Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N

    2009-05-01

    Of 49 long-term care facility residents, 21 (43%) were colonized with 2 or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest that future efforts to efficiently identify the diversity of colonizing strains will be challenging.

  10. Radiation-induced mucositis pain in laryngeal cancer

    International Nuclear Information System (INIS)

    Takahashi, Atsuhito; Shoji, Kazuhiko; Iki, Takehiro; Mizuta, Masanobu; Matsubara, Mami

    2009-01-01

    Radiation therapy in those with head and neck malignancies often triggers painful mucositis poorly controlled by nonsteroidal antiinflammatory drugs (NSAIDs). To better understand how radiation-induced pain develops over time, we studied the numerical rating scale (NRS 0-5) pain scores from 32 persons undergoing radiation therapy of 60-72 Gy for newly diagnosed laryngeal cancer. The degree of mucositis was evaluated using Common Terminology Criteria for Adverse Events version3.0 (CTCAE v3.0). We divided the 32 into a conventional fractionation (CF) group of 14 and a hyperfractionation (HF) group of 18, and further divided laryngeal cancer into a small-field group of 23 and a large-field group of 9. The mucositis pain course was similar in CF and HF, but mucositis pain was severer in the HF group, which also required more NSAIDs. Those in the large-field group had severer pain and mucositis and required more NSAIDs than those in the small-field group. We therefore concluded that small/large-field radiation therapy, rather fractionation type, was related to the incidence of radiation-induced mucositis pain. (author)

  11. Differential Apoptosis in Mucosal and Dermal Wound Healing

    Science.gov (United States)

    Johnson, Ariel; Francis, Marybeth; DiPietro, Luisa Ann

    2014-01-01

    Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase–polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; phealing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing. PMID:25493209

  12. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon.

    Science.gov (United States)

    Ward, Joseph B J; Lajczak, Natalia K; Kelly, Orlaith B; O'Dwyer, Aoife M; Giddam, Ashwini K; Ní Gabhann, Joan; Franco, Placido; Tambuwala, Murtaza M; Jefferies, Caroline A; Keely, Simon; Roda, Aldo; Keely, Stephen J

    2017-06-01

    Ward JB, Lajczak NK, Kelly OB, O'Dwyer AM, Giddam AK, Ní Gabhann J, Franco P, Tambuwala MM, Jefferies CA, Keely S, Roda A, Keely SJ. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am J Physiol Gastrointest Liver Physiol 312: G550-G558, 2017. First published March 30, 2017; doi:10.1152/ajpgi.00256.2016.-Inflammatory bowel diseases (IBD) comprise a group of common and debilitating chronic intestinal disorders for which currently available therapies are often unsatisfactory. The naturally occurring secondary bile acid, ursodeoxycholic acid (UDCA), has well-established anti-inflammatory and cytoprotective actions and may therefore be effective in treating IBD. We aimed to investigate regulation of colonic inflammatory responses by UDCA and to determine the potential impact of bacterial metabolism on its therapeutic actions. The anti-inflammatory efficacy of UDCA, a nonmetabolizable analog, 6α-methyl-UDCA (6-MUDCA), and its primary colonic metabolite lithocholic acid (LCA) was assessed in the murine dextran sodium sulfate (DSS) model of mucosal injury. The effects of bile acids on cytokine (TNF-α, IL-6, Il-1β, and IFN-γ) release from cultured colonic epithelial cells and mouse colonic tissue in vivo were investigated. Luminal bile acids were measured by gas chromatography-mass spectrometry. UDCA attenuated release of proinflammatory cytokines from colonic epithelial cells in vitro and was protective against the development of colonic inflammation in vivo. In contrast, although 6-MUDCA mimicked the effects of UDCA on epithelial cytokine release in vitro, it was ineffective in preventing inflammation in the DSS model. In UDCA-treated mice, LCA became the most common colonic bile acid. Finally, LCA treatment more potently inhibited epithelial cytokine release and protected against DSS-induced mucosal inflammation than did UDCA. These studies identify a new role for the primary metabolite of UDCA, LCA, in preventing colonic

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

    Science.gov (United States)

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

    2009-12-01

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

  14. Bone Marrow Cell Therapy on 1,2-Dimethylhydrazine (DMH)-Induced Colon Cancer in Rats.

    Science.gov (United States)

    El-Khadragy, Manal F; Nabil, Heba M; Hassan, Basmaa N; Tohamy, Amany A; Waaer, Hanaa F; Yehia, Hany M; Alharbi, Afra M; Moneim, Ahmed Esmat Abdel

    2018-01-01

    Stem cell based therapies are being under focus due to their possible role in treatment of various tumors. Bone marrow stem cells believed to have anticancer potential and are preferred for their activities by stimulating the immune system, migration to the site of tumor and ability for inducting apoptosis in cancer cells. The current study was aimed to investigate the tumor suppressive effects of bone marrow cells (BMCs) in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats. The rats were randomly allocated into four groups: control, BMCs alone, DMH alone and BMCs with DMH. BMCs were injected intrarectally while DMH was injected subcutaneously at 20 mg/kg body weight once a week for 15 weeks. Histopathological examination and gene expression of survivin, β-catenin and multidrug resistance-1 (MDR-1) by real-time reverse transcription-polymerase chain reaction (RT-PCR) in rat colon tissues. This is in addition to oxidative stress markers in colon were performed across all groups. The presence of aberrant crypt foci was reordered once histopathological examination of colon tissue from rats which received DMH alone. Administration of BMCs into rats starting from zero-day of DMH injection improved the histopathological picture which showed a clear improvement in mucosal layer, few inflammatory cells infiltration periglandular and in the lamina propria. Gene expression in rat colon tissue demonstrated that BMCs down-regulated survivin, β-catenin, MDR-1 and cytokeratin 20 genes expression in colon tissues after colon cancer induction. Amelioration of the colon status after administration of MSCs has been evidenced by a major reduction of lipid peroxidation, nitric oxide, and increasing of glutathione content and superoxide dismutase along with catalase activities. Our findings demonstrated that BMCs have tumor suppressive effects in DMH-induced colon cancer as evidenced by down-regulation of survivin, β-catenin, and MDR-1 genes and enhancing the antioxidant

  15. Protein-losing Enteropathy Caused by Intestinal or Colonic Lymphangiectasia Complicated by Sporadic Lymphangioleiomyomatosis: A Report of Two Cases.

    Science.gov (United States)

    Nishino, Koichi; Yoshimi, Kaku; Shibuya, Tomoyoshi; Hayashi, Takuo; Mitani, Keiko; Kobayashi, Etsuko; Ichikawa, Masako; Asao, Tetsuhiko; Suzuki, Yohei; Sato, Tadashi; Shiota, Satomi; Kodama, Yuzo; Takahashi, Kazuhisa; Seyama, Kuniaki

    2017-01-01

    This report describes two patients with sporadic lymphangioleiomyomatosis complicated by protein-losing enteropathy (PLE). Imaging studies indicated retroperitoneal lymphangioleiomyomas and abnormalities of the adjacent digestive tract. Endoscopic mucosal biopsy revealed colonic lymphangiectasia in one patient; whereas the site in the other patient was intestinal. Treatment with sirolimus led to the complete resolution of PLE within several months; additionally, marked shrinkage was observed in the lymphangioleiomyomas of both cases. These findings suggest that colonic or intestinal lymphatic congestion due to neighboring lymphangioleiomyomas was the mechanism for the development of PLE. At the time of writing this report, the beneficial effect of sirolimus has lasted for more than 3 years.

  16. Outcomes of colon resection in patients with metastatic colon cancer.

    Science.gov (United States)

    Moghadamyeghaneh, Zhobin; Hanna, Mark H; Hwang, Grace; Mills, Steven; Pigazzi, Alessio; Stamos, Michael J; Carmichael, Joseph C

    2016-08-01

    Patients with advanced colorectal cancer have a high incidence of postoperative complications. We sought to identify outcomes of patients who underwent resection for colon cancer by cancer stage. The National Surgical Quality Improvement Program database was used to evaluate all patients who underwent colon resection with a diagnosis of colon cancer from 2012 to 2014. Multivariate logistic regression analysis was performed to investigate patient outcomes by cancer stage. A total of 7,786 colon cancer patients who underwent colon resection were identified. Of these, 10.8% had metastasis at the time of operation. Patients with metastatic disease had significantly increased risks of perioperative morbidity (adjusted odds ratio [AOR]: 1.44, P = .01) and mortality (AOR: 3.72, P = .01). Patients with metastatic disease were significantly younger (AOR: .99, P colon cancer have metastatic disease. Postoperative morbidity and mortality are significantly higher than in patients with localized disease. Published by Elsevier Inc.

  17. Electrochemical fecal pellet sensor for simultaneous real-time ex vivo detection of colonic serotonin signalling and motility

    Science.gov (United States)

    Morris, Rachel; Fagan-Murphy, Aidan; MacEachern, Sarah J.; Covill, Derek; Patel, Bhavik Anil

    2016-03-01

    Various investigations have focused on understanding the relationship between mucosal serotonin (5-HT) and colonic motility, however contradictory studies have questioned the importance of this intestinal transmitter. Here we described the fabrication and use of a fecal pellet electrochemical sensor that can be used to simultaneously detect the release of luminal 5-HT and colonic motility. Fecal pellet sensor devices were fabricated using carbon nanotube composite electrodes that were housed in 3D printed components in order to generate a device that had shape and size that mimicked a natural fecal pellet. Devices were fabricated where varying regions of the pellet contained the electrode. Devices showed that they were stable and sensitive for ex vivo detection of 5-HT, and no differences in the fecal pellet velocity was observed when compared to natural fecal pellets. The onset of mucosal 5-HT was observed prior to the movement of the fecal pellet. The release of mucosal 5-HT occurred oral to the fecal pellet and was linked to the contraction of the bowel wall that drove pellet propulsion. Taken, together these findings provide new insights into the role of mucosal 5-HT and suggest that the transmitter acts as a key initiator of fecal pellet propulsion.

  18. Transcriptome analysis reveals regional and temporal differences in mucosal immune system development in the small intestine of neonatal calves.

    Science.gov (United States)

    Liang, Guanxiang; Malmuthuge, Nilusha; Bao, Hua; Stothard, Paul; Griebel, Philip J; Guan, Le Luo

    2016-08-11

    Postnatal development of the mammalian mucosal immune system is crucial for responding to the rapid colonization by commensal bacteria and possible exposure to pathogens. This study analyzed expression patterns for mRNAs and their relationship with microRNAs (miRNAs) in the bovine small intestine during the critical neonatal period (0 to 42 days). This analysis revealed molecular mechanisms regulating the postnatal development of the intestinal mucosal immune system. Small intestine samples (jejunum and ileum) were collected from newborn male, Holstein calves immediately post-partum (n = 3) and at 7 (n = 5), 21 (n = 5), and 42 (n = 5) days of age and the transcriptomes were profiled using RNA-Seq. When analyzing all time points collectively, greater expression of genes encoding the complement functional pathway, as well as lower expression of genes encoding Toll-like receptors and NOD-like receptors were observed in the jejunum when compared to the ileum. In addition, significant changes in the expression of immune-related genes were detected within the first week post-partum in both jejunum and ileum. For example, increased expression of genes encoding tight junction proteins (claudin 1, claudin 4 and occludin), an antimicrobial peptide (Regenerating Islet-Derived 3-γ), NOD-like receptors (NACHT, LRR and PYD domain-containing protein 3), regulatory T cell marker (forkhead box P3), and both anti-inflammatory (interleukin 10) and pro-inflammatory (interleukin 8) cytokines was observed throughout the small intestine of 7-day-old calves when compared to newborn calves. Moreover, the expression of mucosal immune-related genes were either positively or negatively correlated with total bacterial population depending on both intestinal region and age. The integrated analysis of miRNAs and mRNAs supported the conclusion that miRNAs may regulate temporal changes in the expression of genes encoding tight junction proteins (miR-335), cytokines (miR-335) and

  19. Protein energy malnutrition alters mucosal IgA responses and reduces mucosal vaccine efficacy in mice.

    Science.gov (United States)

    Rho, Semi; Kim, Heejoo; Shim, Seung Hyun; Lee, Seung Young; Kim, Min Jung; Yang, Bo-Gie; Jang, Myoung Ho; Han, Byung Woo; Song, Man Ki; Czerkinsky, Cecil; Kim, Jae-Ouk

    2017-10-01

    Oral vaccine responsiveness is often lower in children from less developed countries. Childhood malnutrition may be associated with poor immune response to oral vaccines. The present study was designed to investigate whether protein energy malnutrition (PEM) impairs B cell immunity and ultimately reduces oral vaccine efficacy in a mouse model. Purified isocaloric diets containing low protein (1/10 the protein of the control diet) were used to determine the effect of PEM. PEM increased both nonspecific total IgA and oral antigen-specific IgA in serum without alteration of gut permeability. However, PEM decreased oral antigen-specific IgA in feces, which is consistent with decreased expression of polymeric Immunoglobulin receptor (pIgR) in the small intestine. Of note, polymeric IgA was predominant in serum under PEM. In addition, PEM altered B cell development status in the bone marrow and increased the frequency of IgA-secreting B cells, as well as IgA secretion by long-lived plasma cells in the small intestinal lamina propria. Moreover, PEM reduced the protective efficacy of the mucosally administered cholera vaccine and recombinant attenuated Salmonella enterica serovar Typhimurium vaccine in a mouse model. Our results suggest that PEM can impair mucosal immunity where IgA plays an important role in host protection and may partly explain the reduced efficacy of oral vaccines in malnourished subjects. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  20. Immunization of Mice with Lactobacillus casei Expressing a Beta-Intimin Fragment Reduces Intestinal Colonization by Citrobacter rodentium ▿ †

    OpenAIRE

    Ferreira, P. C. D.; da Silva, J. B.; Piazza, R. M. F.; Eckmann, L.; Ho, P. L.; Oliveira, M. L. S.

    2011-01-01

    Enteropathogenic Escherichia coli (EPEC) is a common cause of diarrhea in children from developing countries. Intimate adhesion of the bacteria to intestinal cells occurs via binding of the adhesin intimin to the TIR receptor exposed on cell surfaces. Here, Lactobacillus casei expressing a fragment of β-intimin (L. casei-Intcv) was tested as mucosal vaccines in mice against intestinal colonization with the murine pathogen Citrobacter rodentium. Oral or sublingual immunization of C57BL/6 mice ...

  1. Underwater colorectal EMR: remodeling endoscopic mucosal resection.

    Science.gov (United States)

    Curcio, Gabriele; Granata, Antonino; Ligresti, Dario; Tarantino, Ilaria; Barresi, Luca; Liotta, Rosa; Traina, Mario

    2015-05-01

    Underwater EMR (UEMR) has been reported as a new technique for the removal of large sessile colorectal polyps without need for submucosal injection. To evaluate (1) outcomes of UEMR, (2) whether UEMR can be easily performed by an endoscopist skilled in traditional EMR without specific dedicated training in UEMR, and (3) whether EUS is required before UEMR. Prospective, observational study. Single, tertiary-care referral center. Underwater EMR. Complete resection and adverse events. A total of 72 consecutive patients underwent UEMR of 81 sessile colorectal polyps. EUS was performed before UEMR in 9 cases (11.1%) with a suspicious mucosal/vascular pattern. The mean polyp size was 18.7 mm (range 10-50 mm); the mean UEMR time was 11.8 minutes. Fifty-five polyps (68%) were removed en bloc, and 26 (32%) were removed with a piecemeal technique. Histopathology consisted of tubular adenomas (25.9%), tubulovillous adenomas (5%), adenomas with high-grade dysplasia (42%), serrated polyps (4.9%), carcinoma in situ (13.6%), and hyperplastic polyps (8.6%). Surveillance colonoscopy was scheduled at 3 months. Complete resection was successful in all patients. No adverse events or recurrence was recorded in any of the patients. Limited follow-up; single-center, uncontrolled study. Interventional endoscopists skilled in conventional EMR performed UEMR without specific dedicated training. EUS may not be required for lesions with no invasive features on high-definition narrow-band imaging. UEMR appears to be an effective and safe alternative to traditional EMR and could eventually improve the way in which we can effectively and safely treat colorectal lesions. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  2. [Brazilian colonization in the Paraguayan agricultural frontier].

    Science.gov (United States)

    Neupert, R F

    1991-04-01

    This work briefly describes Brazilian colonization of the Paraguayan agricultural frontier, analyzes factors responsible for expelling population from Brazil and for attracting Brazilians to Paraguay, and assesses the economic and social consequences of immigration to the area. Paraguay's vast and sparsely populated agricultural frontier in areas outside the Central subregion underwent a process of intense colonization from the early 1960s to the mid-1980s. The Paraguayan government initiated an ambitious colonization program in 1963 to increase production, relieve population pressure and subdivision of small parcels in the Central subregion, encourage agricultural modernization, and produce a more diversified agriculture. Paraguayan agriculture in the early 1960s suffered from excessive concentration of land in a few hands and resulting exclusion of around 3/4 of workers from ownership and from any possibility of obtaining credit to fund technological improvements. Results of studies 2 decades after implementation of the colonization plan suggest that it has failed in significant areas. Although a considerable population redistribution alleviated pressure in the Central subregion, it apparently resulted more from spontaneous movement of peasants outside the colonization areas than from the official program. Concentration of lands is now occurring in the colonization area. Assistance for agricultural modernization and diversification of production in the peasant sector has been minimal. On the other hand, production of soy, wheat, and cotton for export increased substantially, because of an entrepreneurial agriculture capitalized by foreign as well as national interests The unmet goals of the colonization program would have required structural reforms rather than simple spatial redistribution of the population. Many of the colonists in the 1970s were Brazilian families displaced by mechanized agriculture in the southern states of Parana, Santa Catarina, and Rio

  3. Colonic motility and enema spreading

    International Nuclear Information System (INIS)

    Hardy, J.G.; Wood, E.; Clark, A.G.; Reynolds, J.R.; Queen's Medical Centre, Nottingham

    1986-01-01

    Radiolabelled enema solution was administered to eight healthy subjects, both in fasted and fed states. Enema spreading was monitored over a 4-h period using gamma scintigraphy and colonic motility was recorded simultaneously using a pressure sensitive radiotelemetry capsule. The rate and extent of enema dispersion were unaffected by eating. Spreading could be correlated with colonic motility and was inhibited by aboral propulsion of the colonic contents. (orig.)

  4. Vasohibin-1 suppresses colon cancer

    OpenAIRE

    Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

    2015-01-01

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor. However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and co...

  5. Diffuse hemangioma of the colon

    International Nuclear Information System (INIS)

    Reis, J.; Caseiro-Alves, F.; Cruz, L.; Moreira, A.; Rebelo, O.

    1995-01-01

    We report two cases of diffuse hemangioma of the colon in adolescent patients. One patient had multiple phleboliths at the lower pelvis identified with plain radiographs of the abdomen. Several aspects were seen on double-contrast enema: luminal narrowing, colonic-wall thickening and submucosal colonic masses that changed in appearance with the degree of colonic distension. Angiography was inconclusive in one case. Use of CT and MR provided relevant information regarding the true extent of the disease, but MR was superior in demonstrating unequivocally the vascular nature of the lesions. (orig.)

  6. Necrotizing Enterocolitis is associated with Ureaplasma Colonization in Preterm Infants

    Science.gov (United States)

    Okogbule-Wonodi, Adora C.; Gross, George W.; Sun, Chen-Chih J.; Agthe, Alexander G.; Xiao, Li; Waites, Ken B.; Viscardi, Rose Marie

    2014-01-01

    The study objective was to determine whether Ureaplasma respiratory tract colonization of preterm infants Ureaplasma culture and PCR were obtained during the first week of life from 368 infants Ureaplasma-positive (12.3%) than Ureaplasma-negative infants (5.5%) Ureaplasma-positive (14.6%) than Ureaplasma-negative (4.4%) infants ≤28 wks (OR 3.67, 95%CI 1.36-9.93, P=0.01). Age of onset, hematologic parameters at onset, and NEC severity were similar between Ureaplasma-positive and negative infants. Cord serum IL-6 and IL-1β concentrations were significantly higher in Ureaplasma-positive than in Ureaplasma-negative NEC-affected infants. Ureaplasma may be a factor in NEC pathogenesis in preterm infants by contributing to intestinal mucosal injury and/or altering systemic or local immune responses. PMID:21258263

  7. Compartment-specific immunity in the human gut: properties and functions of dendritic cells in the colon versus the ileum.

    Science.gov (United States)

    Mann, Elizabeth R; Bernardo, David; English, Nicholas R; Landy, Jon; Al-Hassi, Hafid O; Peake, Simon T C; Man, Ripple; Elliott, Timothy R; Spranger, Henning; Lee, Gui Han; Parian, Alyssa; Brant, Steven R; Lazarev, Mark; Hart, Ailsa L; Li, Xuhang; Knight, Stella C

    2016-02-01

    Dendritic cells (DC) mediate intestinal immune tolerance. Despite striking differences between the colon and the ileum both in function and bacterial load, few studies distinguish between properties of immune cells in these compartments. Furthermore, information of gut DC in humans is scarce. We aimed to characterise human colonic versus ileal DC. Human DC from paired colonic and ileal samples were characterised by flow cytometry, electron microscopy or used to stimulate T cell responses in a mixed leucocyte reaction. A lower proportion of colonic DC produced pro-inflammatory cytokines (tumour necrosis factor-α and interleukin (IL)-1β) compared with their ileal counterparts and exhibited an enhanced ability to generate CD4(+)FoxP3(+)IL-10(+) (regulatory) T cells. There were enhanced proportions of CD103(+)Sirpα(-) DC in the colon, with increased proportions of CD103(+)Sirpα(+) DC in the ileum. A greater proportion of colonic DC subsets analysed expressed the lymph-node-homing marker CCR7, alongside enhanced endocytic capacity, which was most striking in CD103(+)Sirpα(+) DC. Expression of the inhibitory receptor ILT3 was enhanced on colonic DC. Interestingly, endocytic capacity was associated with CD103(+) DC, in particular CD103(+)Sirpα(+) DC. However, expression of ILT3 was associated with CD103(-) DC. Colonic and ileal DC differentially expressed skin-homing marker CCR4 and small-bowel-homing marker CCR9, respectively, and this corresponded to their ability to imprint these homing markers on T cells. The regulatory properties of colonic DC may represent an evolutionary adaptation to the greater bacterial load in the colon. The colon and the ileum should be regarded as separate entities, each comprising DC with distinct roles in mucosal immunity and imprinting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. A randomised clinical trial of misoprostol for radiation mucositis

    International Nuclear Information System (INIS)

    Faroudi, F.; Timms, I.; Sathiyuaseelan, Y.; Cakir, B.; Tiver, K.W.; Gebski, V.; Veness, M.

    2003-01-01

    Radiation mucositis is a major acute toxicity of radiation therapy for head and neck malignancies. We tested whether Misoprostol, a synthetic prostaglandin E 1 analogue given prophylactically decreased intensity of radiation mucositis. A double blind randomized trial was conducted. The intervention consisted of swishing dissolved drug or placebo as a mouthwash, and then swallowing two hours prior to radiation treatment. Patients were stratified based on concurrent chemotherapy, altered fractionation, smoking, extent of oral mucosa in radiation field, and institution. The main end point was the extent of RTOG grade III mucositis, taking into account both time and duration of mucositis. 42 patients were randomized to active drug, and 41 patients to placebo. The trial was designed to have 70 patients in each arm. The trial closed due to poor accrual. In the Misoprostol group 18/42 (43%) had grade III/IV mucositis, and in the placebo group 17/40 (42%). The mean difference between the areas under the curve was 0.38 (p-value: 0.38). For grade II mucositis the corresponding figures were 18 (42%) and 19 (47%). The time from commencement of radiation therapy to the development of peak mucositis was 49 days in the misoprostol patients and 51 days in the placebo group. The duration of grade III mucositis 12.5 days in the Misoprostol patients and 7 days in the placebo patients. In the Misoprostol arm 4 patients had an interruption to their Radiation Therapy, in the Placebo arm 5 had interruptions. Patients average weight loss was 8.1 and 8.2kg. Average self-assessment was via a 10cm LASA scale for soreness of throat and overall well-being. Misoprostol showed a worse QoL on soreness of mouth (mean difference: 0.84 units (p-value .03), but overall well-being was similar on both treatment arms 1 patient withdrew in the Misoprostol arm and 2 in the placebo arm. Misoprostol given prophylactically does not reduce the incidence of Grade III/IV mucositis, is associated with a shorter

  9. CCR2 mediates Helicobacter pylori-induced immune tolerance and contributes to mucosal homeostasis.

    Science.gov (United States)

    Sun, Xia; Zhang, Min; El-Zaatari, Mohamad; Huffnagle, Gray B; Kao, John Y

    2017-04-01

    We previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection. CCR2 deficient (CCR2KO) mice and wild-type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrow-derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H. pylori were examined to determine the impact of CCR2 signaling on dendritic cells function by qPCR, ELISA, and FACS analyses. Acute H. pylori infection was associated with a threefold increase in CCR2 mRNA expression in the gastric mucosa. H. pylori-infected CCR2KO mice exhibited a higher degree of mucosal inflammation, that is, increased gastritis scores and pro-inflammatory cytokine mRNA levels, but lower degree of H. pylori gastric colonization compared to infected Wt mice. Peripheral H. pylori-specific immune response measured in the CCR2KO spleen was characterized by a higher Th17 response and a lower Treg response. In vitro, CCR2KO bone marrow-derived DC was less mature and shown a lower Treg/Th17 ratio. Moreover, blockade of CCR2 signaling by MCP-1 neutralizing antibody inhibited H. pylori-stimulated bone marrow-derived DC maturation. Our results indicate that CCR2 plays an essential role in H. pylori-induced immune tolerance and shed light on a novel mechanism of CCR2-dependent DC Treg induction, which appears to be important in maintaining mucosal homeostasis during H. pylori infection. © 2016 John Wiley & Sons Ltd.

  10. Predictive computational modeling of the mucosal immune responses during Helicobacter pylori infection.

    Directory of Open Access Journals (Sweden)

    Adria Carbo

    Full Text Available T helper (Th cells play a major role in the immune response and pathology at the gastric mucosa during Helicobacter pylori infection. There is a limited mechanistic understanding regarding the contributions of CD4+ T cell subsets to gastritis development during H. pylori colonization. We used two computational approaches: ordinary differential equation (ODE-based and agent-based modeling (ABM to study the mechanisms underlying cellular immune responses to H. pylori and how CD4+ T cell subsets influenced initiation, progression and outcome of disease. To calibrate the model, in vivo experimentation was performed by infecting C57BL/6 mice intragastrically with H. pylori and assaying immune cell subsets in the stomach and gastric lymph nodes (GLN on days 0, 7, 14, 30 and 60 post-infection. Our computational model reproduced the dynamics of effector and regulatory pathways in the gastric lamina propria (LP in silico. Simulation results show the induction of a Th17 response and a dominant Th1 response, together with a regulatory response characterized by high levels of mucosal Treg cells. We also investigated the potential role of peroxisome proliferator-activated receptor γ (PPARγ activation on the modulation of host responses to H. pylori by using loss-of-function approaches. Specifically, in silico results showed a predominance of Th1 and Th17 cells in the stomach of the cell-specific PPARγ knockout system when compared to the wild-type simulation. Spatio-temporal, object-oriented ABM approaches suggested similar dynamics in induction of host responses showing analogous T cell distributions to ODE modeling and facilitated tracking lesion formation. In addition, sensitivity analysis predicted a crucial contribution of Th1 and Th17 effector responses as mediators of histopathological changes in the gastric mucosa during chronic stages of infection, which were experimentally validated in mice. These integrated immunoinformatics approaches

  11. A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis

    Directory of Open Access Journals (Sweden)

    Bryan Oronsky

    2018-06-01

    Full Text Available The first tenet of medicine, “primum non nocere” or “first, do no harm”, is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonly result in significant toxicities. One of the more frequent and serious treatment-induced toxicities is mucositis and particularly oral mucositis (OM described as inflammation, atrophy and breakdown of the mucosa or lining of the oral cavity. The sequelae of oral mucositis (OM, which include pain, odynodysphagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions and discontinuations that not only negatively impact quality of life but also tumor control and survivorship. One potential strategy to reduce or prevent the development of mucositis, for which no effective therapies exist only best supportive empirical care measures, is the administration of agents referred to as radioprotectors and/or chemoprotectors, which are intended to differentially protect normal but not malignant tissue from cytotoxicity. This limited-scope review briefly summarizes the incidence, pathogenesis, symptoms and impact on patients of OM as well as the background and mechanisms of four clinical stage radioprotectors/chemoprotectors, amifostine, palifermin, GC4419 and RRx-001, with the proven or theoretical potential to minimize the development of mucositis particularly in the treatment of head and neck cancers.

  12. MALToma of the Transverse colon, Ascending colon and Caecum: A ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    RESULT. We herein report a case of a 40-year-old male with mucosa - associated lymphoid tissue. [MALT] lymphoma of the transverse colon, ascending colon and caecum. He presented with severe abdominal pains and a centrally located huge abdominal mass for which a surgical resection was done. Histologically.

  13. Telomere shortening in the colonic mucosa of patients with ulcerative colitis.

    Science.gov (United States)

    Kinouchi, Y; Hiwatashi, N; Chida, M; Nagashima, F; Takagi, S; Maekawa, H; Toyota, T

    1998-06-01

    Telomere length in human somatic cells gradually decreases with the number of cell divisions and is regarded as a marker of somatic cell turnover. Mucosal cells of the affected colon show rapid turnover in individuals with active ulcerative colitis (UC). Telomere length was determined by Southern blot analysis of terminal restriction fragments (TRFs) from the colonic mucosa of 17 patients with UC in remission, two of whom showed dysplasia, and 17 control subjects without colitis. For each individual, mean TRF length was compared between rectal mucosa and unaffected cecal mucosa. The mean TRF length of the rectal mucosa was significantly less than that of cecal mucosa in UC patients (7.87 +/- 0.36kb versus 8.77 +/- 0.21 kb; P = 0.0015, Wilcoxon signed rank test), whereas no significant difference was detected in the control subjects. The extent of telomere shortening was 10.6 +/- 3.35% in UC patients, compared with 0.8 +/- 0.64% in noncolitis controls (P = 0.0024, Mann-Whitney U-test). Four UC patients, two of whom had dysplasia, showed telomere shortening of more than 20% in the rectal mucosa. These observations suggest that telomere shortening in the colonic mucosa of individuals with UC may represent the history of mucosal inflammation during disease of long duration, and that it may contribute to aneuploidy in UC.

  14. Complete mucosal healing of distal lesions induced by twice-daily budesonide 2-mg foam promoted clinical remission of mild-to-moderate ulcerative colitis with distal active inflammation: double-blind, randomized study.

    Science.gov (United States)

    Naganuma, Makoto; Aoyama, Nobuo; Tada, Tomohiro; Kobayashi, Kiyonori; Hirai, Fumihito; Watanabe, Kenji; Watanabe, Mamoru; Hibi, Toshifumi

    2018-04-01

    Budesonide foam is used for the topical treatment of distal ulcerative colitis. This phase III study was performed to confirm mucosal healing and other therapeutic effects of twice-daily budesonide 2-mg foam in patients with mild-to-moderate ulcerative colitis including left-sided colitis and pancolitis. This was a multicenter, randomized, placebo-controlled, double-blind trial. A total of 126 patients with mild-to-moderate ulcerative colitis with active inflammation in the distal colon were randomized to two groups receiving twice-daily budesonide 2 mg/25 ml foam or placebo foam. The primary endpoint was the percentage of complete mucosal healing of distal lesions (endoscopic subscore of 0) at week 6. Some patients continued the treatment through week 12. Drug efficacy and safety were evaluated. The percentages of both complete mucosal healing of distal lesions and clinical remission were significantly improved in the budesonide as compared with the placebo group (p = 0.0003 and p = 0.0035). Subgroup analysis showed similar efficacy of budesonide foam for complete mucosal healing of distal lesions and clinical remission regardless of disease type. The clinical remission percentage tended to be higher in patients achieving complete mucosal healing of distal lesions than in other patients. There were no safety concerns with budesonide foam. This study confirmed for the first time complete mucosal healing with twice-daily budesonide 2-mg foam in mild-to-moderate ulcerative colitis with distal active inflammation. The results also indicated that complete mucosal healing of distal lesions by budesonide foam promotes clinical remission of ulcerative colitis. Clinical trial registration no.: Japic CTI-142704.

  15. Peptic ulcer pathophysiology: acid, bicarbonate, and mucosal function

    DEFF Research Database (Denmark)

    Højgaard, L; Mertz Nielsen, A; Rune, S J

    1996-01-01

    The previously accepted role of gastric acid hypersecretion in peptic ulcer disease has been modified by studies showing no correlation between acid output and clinical outcome of ulcer disease, or between ulcer recurrence rate after vagotomy and preoperative acid secretion. At the same time......, studies have been unable to demonstrate increased acidity in the duodenal bulb in patients with duodenal ulcer, and consequently more emphasis has been given to the mucosal protecting mechanisms. The existence of an active gastric and duodenal mucosal bicarbonate secretion creates a pH gradient from...... cell removal and repair regulated by epidermal growth factor. Sufficient mucosal blood flow, including a normal acid/base balance, is important for subepithelial protection. In today's model of ulcer pathogenesis, gastric acid and H. pylori work in concert as aggressive factors, with the open question...

  16. Endomicroscopy for assessing mucosal healing in patients with ulcerative colitis.

    Science.gov (United States)

    Gheorghe, Cristian; Cotruta, Bogdan; Iacob, Razvan; Becheanu, Gabriel; Dumbrava, Mona; Gheorghe, Liana

    2011-12-01

    The assessment of tissue healing has emerged as an important treatment goal in patients with inflammatory bowel disease. In patients with ulcerative colitis (UC), mucosal healing may represent the ultimate therapeutic goal due to the fact that the inflammation is limited to the mucosal layer. Mucosal and histological healing may indicate a subset of UC patients in long-term clinical, endoscopic and histological remission in whom immunomodulators, biologics, and even aminosalicylates may be withdrawn. Confocal laser endomicroscopy allows the assessment of residual cellular inflammation, crypt and vessel architecture distortion during ongoing endoscopy, and therefore permits a real-time evaluation of histological healing in patients with ulcerative proctitis. Images of conventional optical microscopy and confocal laser endomicroscopy in patients with ulcerative proctitis in remission are presented.

  17. Oral mucositis: recent perspectives on prevention and treatment

    Directory of Open Access Journals (Sweden)

    Paulo Sérgio da Silva Santos

    2009-10-01

    Full Text Available Oral mucositis is a result of toxicity and one of the most common side effects of radiotherapy and chemotherapy in cancer treatment and in hematopoietic stem cell transplantation. Clinically these changes are characterized by epithelial atrophy, edema, erythema and the appearance of ulcerations that can affect the entire oral mucosa, causing pain and discomfort, impairing speech, and swallowing food. In addition to the major symptoms, the ulcers increase the risk of local and systemic infection, compromising function and interfering with oral antineoplastic treatment and may lead to it being discontinued. The diagnosis, prevention and therapeutic strategies in providing support in cases of oral mucositis are the dentist’s responsibility. Through critical analysis of literature, the aim of this article is to present oral mucositis, its pathogenesis, clinical features and treatments offered today to address or control the condition, highlighting the importance of dentists’ role in its management.

  18. Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells.

    Science.gov (United States)

    Lajczak, Natalia K; Saint-Criq, Vinciane; O'Dwyer, Aoife M; Perino, Alessia; Adorini, Luciano; Schoonjans, Kristina; Keely, Stephen J

    2017-09-01

    Bile acids and epithelial-derived human β-defensins (HβDs) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic HβD expression and aimed to test this by investigating the effects of deoxycholic acid (DCA) and ursodeoxycholic acid on the expression and release of HβD1 and HβD2 from colonic epithelial cells and mucosal tissues. DCA (10-150 µM) stimulated the release of both HβD1 and HβD2 from epithelial cell monolayers and human colonic mucosal tissue in vitro In contrast, ursodeoxycholic acid (50-200 µM) inhibited both basal and DCA-induced defensin release. Effects of DCA were mimicked by the Takeda GPCR 5 agonist, INT-777 (50 μM), but not by the farnesoid X receptor agonist, GW4064 (10 μM). INT-777 also stimulated colonic HβD1 and HβD2 release from wild-type, but not Takeda GPCR 5 -/- , mice. DCA stimulated phosphorylation of the p65 subunit of NF-κB, an effect that was attenuated by ursodeoxycholic acid, whereas an NF-κB inhibitor, BMS-345541 (25 μM), inhibited DCA-induced HβD2, but not HβD1, release. We conclude that bile acids can differentially regulate colonic epithelial HβD expression and secretion and discuss the implications of our findings for intestinal health and disease.-Lajczak, N. K., Saint-Criq, V., O'Dwyer, A. M., Perino, A., Adorini, L., Schoonjans, K., Keely, S. J. Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells. © FASEB.

  19. Colonic duplication in an adult

    International Nuclear Information System (INIS)

    Baro, P.; Dario Casas, J.; Sanchez, D.

    1988-01-01

    A case of colonic duplication that was diagnosed radiologically in an adult is reported. A long duplicated segment below the normal transverse colon, with a wide anastomosis at the hepatic flexure level, was observed on barium enema. The rarity of this anomaly unassociated with other malformations is emphasized. (orig.)

  20. Prehistoric human colonization of India

    Indian Academy of Sciences (India)

    Unknown

    2. Earliest human colonization of south Asia. The early human colonization of south Asia is represented largely by an abundance of stone tool assemblages. The oldest known tools ..... component among finished tools is conspicuous in the hinterland riverine ...... sativum), green gram (Vigna radiata), gram/chicken pea.

  1. Colonic Diverticulitis in the Elderly

    Directory of Open Access Journals (Sweden)

    Chien-Kuo Liu

    2009-03-01

    Full Text Available Diverticular disease of the colon is a disease that mainly affects the elderly and presents in 50–70% of those aged 80 years or older. The most common complication is colonic diverticulitis. Eighty percent of patients who present with colonic diverticulitis are aged 50 years and older. Diagnosis and treatment of colonic diverticulitis in the elderly is more difficult and complicated owing to more comorbid conditions. Computed tomography is recommended for diagnosis when colonic diverticulitis is suspected. Most patients admitted with acute colonic diverticulitis respond to conservative treatment, but 15–30% of patients require surgery. Because surgery for acute colonic diverticulitis carries significant rates of morbidity and mortality, conservative treatment is recommended in the elderly. Conservative treatment of colonic diverticulitis with antibiotics, bowel rest, possibly including parenteral alimentation, is usually applied for 1–2 weeks. In the absence of a response to conservative treatment, frequent recurrence or complications (abscesses, fistulas, bowel obstructions, and free perforations, surgery is indicated.

  2. Colonic perforation following endoscopic retrograde ...

    African Journals Online (AJOL)

    She developed severe upper abdominal pain after the ... non-surgical management of pancreatitis and associated complications, colonic perforation should be considered in patients who deteriorate ... To our knowledge this is the first case of a secure pre-operative diagnosis of colonic perforation due to to pancreatitis.

  3. Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-09-01

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

  4. The identification of plant lectins with mucosal adjuvant activity

    Science.gov (United States)

    Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O'hagan, D T

    2001-01-01

    To date, the most potent mucosal vaccine adjuvants to be identified have been bacterial toxins. The present data demonstrate that the type 2 ribosome-inactivating protein (type 2 RIP), mistletoe lectin I (ML-I) is a strong mucosal adjuvant of plant origin. A number of plant lectins were investigated as intranasal (i.n.) coadjuvants for a bystander protein, ovalbumin (OVA). As a positive control, a potent mucosal adjuvant, cholera toxin (CT), was used. Co-administration of ML-I or CT with OVA stimulated high titres of OVA-specific serum immunoglobulin G (IgG) in addition to OVA-specific IgA in mucosal secretions. CT and ML-I were also strongly immunogenic, inducing high titres of specific serum IgG and specific IgA at mucosal sites. None of the other plant lectins investigated significantly boosted the response to co-administered OVA. Immunization with phytohaemagglutinin (PHA) plus OVA elicited a lectin-specific response but did not stimulate an enhanced response to OVA compared with the antigen alone. Intranasal delivery of tomato lectin (LEA) elicited a strong lectin-specific systemic and mucosal antibody response but only weakly potentiated the response to co-delivered OVA. In contrast, administration of wheatgerm agglutinin (WGA) or Ulex europaeus lectin 1 (UEA-I) with OVA stimulated a serum IgG response to OVA while the lectin-specific responses (particularly for WGA) were relatively low. Thus, there was not a direct correlation between immunogenicity and adjuvanticity although the strongest adjuvants (CT, ML-I) were also highly immunogenic. PMID:11168640

  5. Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    Science.gov (United States)

    Spivakovsky, Sylvia

    2016-09-01

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

  7. The G-protein coupled chemoattractant receptor FPR2 promotes malignant phenotype of human colon cancer cells

    Science.gov (United States)

    Xiang, Yi; Yao, Xiaohong; Chen, Keqiang; Wang, Xiafei; Zhou, Jiamin; Gong, Wanghua; Yoshimura, Teizo; Huang, Jiaqiang; Wang, Rongquan; Wu, Yuzhang; Shi, Guochao; Bian, Xiuwu; Wang, Jiming

    2016-01-01

    The G-protein coupled chemoattractant receptor formylpeptide receptor-2 (FPR2 in human, Fpr2 in mice) is expressed by mouse colon epithelial cells and plays a critical role in mediating mucosal homeostasis and inflammatory responses. However, the biological role of FPR2 in human colon is unclear. Our investigation revealed that a considerable number of human colon cancer cell lines expressed FPR2 and its ligands promoted cell migration and proliferation. Human colon cancer cell lines expressing high levels of FPR2 also formed more rapidly growing tumors in immunocompromised mice as compared with cell lines expressing lower levels of FPR2. Knocking down of FPR2 from colon cancer cell lines highly expressing FPR2 reduced their tumorigenicity. Clinically, FPR2 is more highly expressed in progressive colon cancer, associated with poorer patient prognosis. These results suggest that FPR2 can be high-jacked by colon cancer cells for their growth advantage, thus becoming a potential target for therapeutic development. PMID:27904774

  8. Investigation of how to prevent mucositis induced by chemoradiotherapy

    International Nuclear Information System (INIS)

    Tosaka, Chihiro; Tajima, Hakuju; Inoue, Tadao

    2011-01-01

    Chemoradiotherapy for head and neck cancer is associated with a high incidence of severe oral mucositis; an adverse, painful event. Oral mucositis also causes nutritional deficiency by making oral feeding difficult. This may lead to prolongation of hospitalization due to complications caused by malnutrition. However, an effective way to prevent oral mucositis completely, remains to be found. In this study, we evaluated the occurrence of oral mucositis, and nutritional conditions such as hypoalbuminemia, reduction of body weight, and length of hospital stay (days) when the mouth was rinsed using rebamipide solution (R solution), or Poraprezinc-alginate sodium solution (P-A solution) (both considered to be effective for oral mucositis). A mouth rinsed with sodium azulene sulfonate (S solution) was used as a control. The mouth was rinsed out six times per day continuously during chemoradiotherapy. In the study, 31 patients were assigned to rinse their mouths using R solution, 11 patients using P-A solution, and 15 patients using S solution (reduction rate of body weight in 14 patients). For the evaluation, the criteria for adverse drug reactions CTCAE (v3.0) were used. Grade 1 and over, oral mucositis occurred in 48% of the R solution group, 36% of the P-A solution group, and 80% of the S solution group, indicating that the P-A solution group significantly prevented the occurrence of oral mucositis as opposed to the S solution group. A reduction in body weight was observed in 81% of the R solution group, 82% of the P-A solution group, and 79% of the S solution group, indicating a similar weight reduction rate among individual solution groups. Hypoalbuminemia equal to grade 2 or higher occurred in 3% of the R solution group, 18% of the P-A solution group, and 29% of the S solution group, indicating that the R group significantly prevented the occurrence of hypoalbuminemia compared to the S solution group. In addition, the length of hospital stays were 44±8.0 days for

  9. Experiences with Pontal syrup in mucositis caused by radiotherapy

    International Nuclear Information System (INIS)

    Miyamoto, Hiroshi; Yamashita, Shoji; Hashimoto, Teisuke; Kunieda, Etsuo; Hashimoto, Shozo

    1983-01-01

    Pontal syrup was administered at daily dose of 30 ml t. i. d. to 17 patients of mucositis developed due to radiotherapy against malignant tumor. Results were: Remarkably effective-5 cases, effective-8 cases, slightly effective-3 cases, and non-effective-1 case. Certain effects were observed in 16 cases out of 17 cases/94.1%, excluding only one non-effective case. No side-effects were observed in all cases. It is considered that Pontal syrup is a drug useful for mucositis caused by radiotherapy because of its easiness of administration and also of its characteristic of non-stimulant. (author)

  10. Intestinal dendritic cells in the regulation of mucosal immunity

    DEFF Research Database (Denmark)

    Bekiaris, Vasileios; Persson, Emma K.; Agace, William Winston

    2014-01-01

    immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive....... The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality...

  11. Psychological factors in oral mucosal and orofacial pain conditions.

    Science.gov (United States)

    Alrashdan, Mohammad S; Alkhader, Mustafa

    2017-01-01

    The psychological aspects of chronic pain conditions represent a key component of the pain experience, and orofacial pain conditions are not an exception. In this review, we highlight how psychological factors affect some common oral mucosal and orofacial pain conditions (namely, oral lichen planus, recurrent aphthous stomatitis, burning mouth syndrome, and temporomandibular disorders) with emphasis on the significance of supplementing classical biomedical treatment modalities with appropriate psychological counseling to improve treatment outcomes in targeted patients. A literature search restricted to reports with highest relevance to the selected mucosal and orofacial pain conditions was carried out to retrieve data.

  12. Indomethacin decreases gastroduodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Bukhave, K

    1995-01-01

    BACKGROUND: Cyclooxygenase inhibitors reduce mucosal bicarbonate secretion in the duodenum, but the evidence for their effect on bicarbonate secretion in the stomach remains controversial. We have, therefore, studied how indomethacin influences gastroduodenal bicarbonate secretion and luminal...... healthy volunteers. Bicarbonate and PGE2 were measured in the gastroduodenal effluents by back-titration and radioimmunoassay, respectively. RESULTS: Vagal stimulation and duodenal luminal acidification (0.1 M HCl; 20 ml; 5 min) increased gastroduodenal bicarbonate secretion (p ... markedly inhibited both basal and stimulated gastric and duodenal mucosal bicarbonate secretion, and this reduction was similar to the degree of cyclooxygenase inhibition estimated by the luminal release of PGE2 (p

  13. Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100-Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

    NARCIS (Netherlands)

    Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

    2013-01-01

    Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery

  14. Optical coherence tomography imaging of colonic crypts in a mouse model of colorectal cancer

    Science.gov (United States)

    Welge, Weston A.; Barton, Jennifer K.

    2016-03-01

    Aberrant crypt foci (ACF) are abnormal epithelial lesions that precede development of colonic polyps. As the earliest morphological change in the development of colorectal cancer, ACF is a highly studied phenomenon. The most common method of imaging ACF is chromoendoscopy using methylene blue as a contrast agent. Narrow- band imaging is a contrast-agent-free modality for imaging the colonic crypts. Optical coherence tomography (OCT) is an attractive alternative to chromoendoscopy and narrow-band imaging because it can resolve the crypt structure at sufficiently high sampling while simultaneously providing depth-resolved data. We imaged in vivo the distal 15 mm of colon in the azoxymethane (AOM) mouse model of colorectal cancer using a commercial swept-source OCT system and a miniature endoscope designed and built in-house. We present en face images of the colonic crypts and demonstrate that different patterns in healthy and adenoma tissue can be seen. These patterns correspond to those reported in the literature. We have previously demonstrated early detection of colon adenoma using OCT by detecting minute thickening of the mucosa. By combining mucosal thickness measurement with imaging of the crypt structure, OCT can be used to correlate ACF and adenoma development in space and time. These results suggest that OCT may be a superior imaging modality for studying the connection between ACF and colorectal cancer.

  15. Case of a sigmoid colon cancer with metachronous metastases to the mesorectum and the abdominal wall

    Directory of Open Access Journals (Sweden)

    Hadjimarcou Andreas

    2010-03-01

    Full Text Available Abstract Backround Sigmoid colon cancer metachronous metastases commonly occur in the liver and lungs with sporadic reports also to the spleen, stomach, thyroid gland, abdominal wall and upper urinary tract. This is a rare case of metachronous metastases invading the mesorectum and the abdominal wall. Case presentation A 72-year-old female underwent sigmoidectomy for stage I (T2N0 M0 sigmoid colon cancer in May 2008. In June 2009, an abdominal computed tomography scan revealed a tumor 2 cm in size at the lower anterior mesorectum and a second mass 2 cm in size at the anterior abdominal wall midline. Total colonoscopy showed no mucosal lesion. The serum carcinoembryonic antigen level was normal. A biopsy of the mesorectum tumor showed similar histologic characteristics with the primary tumor. Since no other site of recurrence was identified, an abdominoperineal resection was attempted. During the operation and after the removal of the incision recurrence, sinus bradycardia and signs of myocardial ischemia were noticed. A loop transverse colostomy was immediately perfomed and the operation was terminated. Postoperative cardiologic examination revealed an acute myocardium infract. Chemo-radiation of the mesorectum tumor and re-evaluation for surgical excision was decided. Conclusion Metachronous metastasis of the mesorectum from sigmoid colon cancer is extremely rare. Although patterns of lymphatic spread from rectal cancer to sigmoid colon have recently been demonstrated, there is no evidence of metachronous mesorectum invasion from sigmoid colon cancer. This could be the issue for future trials.

  16. Kynurenic acid inhibits intestinal hypermotility and xanthine oxidase activity during experimental colon obstruction in dogs.

    Science.gov (United States)

    Kaszaki, J; Palásthy, Z; Erczes, D; Rácz, A; Torday, C; Varga, G; Vécsei, L; Boros, M

    2008-01-01

    Kynurenic acid (KynA), an endogenous antagonist of N-methyl-d-aspartate (NMDA) glutamate receptors, protects the central nervous system in excitotoxic neurological diseases. We hypothesized that the inhibition of enteric glutamate receptors by KynA may influence dysmotility in the gastrointestinal tract. Group 1 of healthy dogs served as the sham-operated control, in group 2, the animals were treated with KynA, while in groups 3 and 4 mechanical colon obstruction was maintained for 7 h. Group 4 was treated with KynA at the onset of ileus. Hemodynamics and motility changes were monitored, and the activities of xanthine oxidoreductase (XOR) and myeloperoxidase (MPO) were determined from tissue samples. Colon obstruction induced a hyperdynamic circulatory reaction, significantly elevated the motility index and increased the mucosal leucocyte accumulation and the XOR activity. The KynA treatment augmented the tone of the colon, permanently decreased the motility index of the giant colonic contractions and reduced the increases in XOR and MPO activities. These effects were concomitant with the in vitro inhibition of XOR activity. In conclusion, KynA antagonizes the obstruction-induced motility responses and XOR activation in the colon. Inhibition of enteric NMDA receptors may provide an option to influence intestinal hypermotility and inflammatory changes.

  17. [On the origin and spread of cutaneous and mucosal leishmaniasis, based on pre- and post- colombian historical source].

    Science.gov (United States)

    Altamirano-Enciso, Alfredo J; Marzochi, Mauro C A; Moreira, João S; Schubach, Armando O; Marzochi, Keyla B F

    2003-01-01

    Drawing from four sixteenth-century sources, the article reports some apparent incidents of American Tegumentary Leishmaniasis within the territory of the Andes. Reinterpretation of these sources affords a look at the longstanding issue of the origin of espundia,or mucosal Leishmaniasis (ML). The study reinforces the hypothesis that ML originated in the western Amazon region, from there climbing into the high forests and later into hot inter-Andean lands via Bolivia's and Peru's borders with Brazil, above al through human migration. dating to archeological times, this process intensified during the Inca period under the social policies of the mitmaq or mitimaes. These events transpired within the historical and social context of the fall of the Inca Empire and the advent of Spanish colonization.

  18. Effect of complex polyphenols and tannins from red wine on DNA oxidative damage of rat colon mucosa in vivo.

    Science.gov (United States)

    Giovannelli, L; Testa, G; De Filippo, C; Cheynier, V; Clifford, M N; Dolara, P

    2000-10-01

    Dietary polyphenols have been reported to have a variety of biological actions, including anti-carcinogenic, antioxidant and anti-inflammatory activities. In the present study we have evaluated the effect of an oral treatment with complex polyphenols and tannins from red wine and tea on DNA oxidative damage in the rat colon mucosa. Isolated colonocytes were prepared from the colon mucosa of rats treated for ten days with either wine complex polyphenols (57.2 mg/kg/d) or thearubigin (40 mg/kg/d) by oral gavage. Colonocyte oxidative DNA damage was analysed at the single cell level using a modification of the comet assay technique. The results show that wine complex polyphenols and tannins induce a significant decrease (-62% for pyrimidine and -57% for purine oxidation) in basal DNA oxidative damage in colon mucosal cells without affecting the basal level of single-strand breaks. On the other hand, tea polyphenols, namely a crude extract of thearubigin, did not affect either strand breaks or pyrimidine oxidation in colon mucosal cells. Our experiments are the first demonstration that dietary polyphenols can modulate in vivo oxidative damage in the gastrointestinal tract of rodents. These data support the hypothesis that dietary polyphenols might have both a protective and a therapeutic potential in oxidative damage-related pathologies.

  19. Colon flattening by landmark-driven optimal quasiconformal mapping.

    Science.gov (United States)

    Zeng, Wei; Yang, Yi-Jun

    2014-01-01

    In virtual colonoscopy, colon conformal flattening plays an important role, which unfolds the colon wall surface to a rectangle planar image and preserves local shapes by conformal mapping, so that the cancerous polyps and other abnormalities can be easily and thoroughly recognized and visualized without missing hidden areas. In such maps, the anatomical landmarks (taeniae coli, flexures, and haustral folds) are naturally mapped to convoluted curves on 2D domain, which poses difficulty for comparing shapes from geometric feature details. Understanding the nature of landmark curves to the whole surface structure is meaningful but it remains challenging and open. In this work, we present a novel and effective colon flattening method based on quasiconformal mapping, which straightens the main anatomical landmark curves with least conformality (angle) distortion. It provides a canonical and straightforward view of the long, convoluted and folded tubular colon surface. The computation is based on the holomorphic 1-form method with landmark straightening constraints and quasiconformal optimization, and has linear time complexity due to the linearity of 1-forms in each iteration. Experiments on various colon data demonstrate the efficiency and efficacy of our algorithm and its practicability for polyp detection and findings visualization; furthermore, the result reveals the geometric characteristics of anatomical landmarks on colon surfaces.

  20. Recombinant interleukin 6 with M cell-targeting moiety produced in Lactococcus lactis IL1403 as a potent mucosal adjuvant for peroral immunization.

    Science.gov (United States)

    Li, Hui-Shan; Piao, Da-Chuan; Jiang, Tao; Bok, Jin-Duck; Cho, Chong-Su; Lee, Yoon-Seok; Kang, Sang-Kee; Choi, Yun-Jaie

    2015-04-15

    Development and application of safe and effective mucosal adjuvants are important to improve immunization efficiency in oral vaccine. Here, we report a novel mucosal adjuvant, IL-6-CKS9, a recombinant cytokine generated by conjugating an M cell-targeting peptide (CKS9) with c-terminus of the murine interleukin 6 (IL-6), which facilitated enhancement of mucosal immune response. Lactococcus lactis IL1403, a food-grade strain of lactic acid bacteria (LAB) which is widely used in dairy industry, was used as a host cell to express and secrete the IL-6-CKS9 for a mucosal vaccine adjuvant. The recombinant L. lactis IL1403 secreting IL-6-CKS9 was orally administered with a model antigen protein, M-BmpB (Brachyspira membrane protein B conjugated with CKS9), to BALB/c mice for mucosal immunization. ELISA analyses showed consistent enhancement tendencies in induction of anti-M-BmpB antibody levels both with mucosal (IgA) and systemic (IgG) immune responses in IL-6-CKS9-LAB treated group compared with other groups tested by conducting two separated mice immunization assays. In addition, we characterized that the oral administration of model protein antigen with live LAB producing IL-6-CKS9 could induce both Th1 and Th2 type immune responses by analysis of the specific anti-BmpB IgG1 and IgG2a isotypes in the sera and also investigated possible oral tolerance in our vaccine strategy. Collectively, our results showed successful production and secretion of recombinant murine IL-6 with M cell-targeting moiety (IL-6-CKS9) from L. lactis IL1403 and demonstrated the live recombinant LAB producing IL-6-CKS9 could have a potential to be used as an efficient adjuvant for peroral vaccination. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. An integrated data model to estimate spatiotemporal occupancy, abundance, and colonization dynamics

    Science.gov (United States)

    Williams, Perry J.; Hooten, Mevin B.; Womble, Jamie N.; Esslinger, George G.; Bower, Michael R.; Hefley, Trevor J.

    2017-01-01

    Ecological invasions and colonizations occur dynamically through space and time. Estimating the distribution and abundance of colonizing species is critical for efficient management or conservation. We describe a statistical framework for simultaneously estimating spatiotemporal occupancy and abundance dynamics of a colonizing species. Our method accounts for several issues that are common when modeling spatiotemporal ecological data including multiple levels of detection probability, multiple data sources, and computational limitations that occur when making fine-scale inference over a large spatiotemporal domain. We apply the model to estimate the colonization dynamics of sea otters (Enhydra lutris) in Glacier Bay, in southeastern Alaska.

  2. Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.

    Science.gov (United States)

    Arias, Mauricio A; Loxley, Andrew; Eatmon, Christy; Van Roey, Griet; Fairhurst, David; Mitchnick, Mark; Dash, Philip; Cole, Tom; Wegmann, Frank; Sattentau, Quentin; Shattock, Robin

    2011-02-01

    Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Environmental and mucosal microbiota and their role in childhood asthma

    NARCIS (Netherlands)

    Birzele, L T; Depner, M.; Ege, M.J.; Engel, M; Kublik, S; Bernau, C; Loss, G J; Genuneit, J.; Horak, E.; Schloter, M; Braun-Fahrländer, C.; Danielewicz, H.; Heederik, D; von Mutius, E.; Legatzki, A

    BACKGROUND: High microbial diversity in the environment has been associated with lower asthma risk, particularly in children exposed to farming. It remains unclear whether this effect operates through an altered microbiome of the mucosal surfaces of the airways. METHODS: DNA from mattress dust and

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

    DEFF Research Database (Denmark)

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian

    2016-01-01

    cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma...

  5. The Mucosal Immune System and Its Regulation by Autophagy.

    Science.gov (United States)

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

    2016-01-01

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

  6. Oral mucositis frequency in head and neck chemoradiotherapy

    International Nuclear Information System (INIS)

    Hata, Hironobu; Ota, Yojiro; Ueno, Takao; Kurihara, Kinue; Nishimura, Tetsuo; Onozawa, Yusuke; Zenda, Sadamoto

    2007-01-01

    A retrospective study was performed to determine the frequency and risk factors of oral mucositis in patients receiving radiotherapy or chemoradiotherapy for head and neck tumors. We classified all patients into three groups according to the radiation dose given in the oral cavity (Group A: 0 Gy; 73 patients, Group B: <40 Gy; 66 patients, Group C: ≥40 Gy; 110 patients). In group C, the odds ratio of oral mucositis (≥Gr.2) was 5.6 times in the concomitant chemotherapy group (62 patients) (odds ratio (OR) of 5.6; 95% confidence interval (CI): 2.1-14.9) compared with the radiotherapy (RT) only group (48 patients). In the case of concomitant chemotherapy group in Group C, the odds ratio of oral mucositis (≥Gr.2) was 17 times (OR of 17.1; 95% CI: 2.8-106.0) that in the group using 5-fluorouracil (FU) (50 patients) compared with the group that did not use it (12 patients). For patients whose accumulated radiation dose in the oral cavity was more than 40 Gy, 5-FU was found to be a significant risk factor for oral mucositis. (author)

  7. Live bacterial delivery systems for development of mucosal vaccines

    NARCIS (Netherlands)

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

    2000-01-01

    By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed

  8. Mucosal vaccination by adenoviruses displaying reovirus sigma 1

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, Eric A. [Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902 (United States); Camacho, Zenaido T. [Department of Cell Biology, Department of Natural Sciences, Western New Mexico University, Silver City, NM 88062 (United States); Hillestad, Matthew L. [Nephrology Training Program, Mayo Clinic, Rochester, MN 55902 (United States); Crosby, Catherine M.; Turner, Mallory A.; Guenzel, Adam J.; Fadel, Hind J. [Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902 (United States); Mercier, George T. [Department of Physics, University of Houston, Houston, TX 77004 (United States); Barry, Michael A., E-mail: mab@mayo.edu [Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902 (United States); Department of Immunology and Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902 (United States)

    2015-08-15

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

  9. C-kit expression in canine mucosal melanomas.

    Science.gov (United States)

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

    2012-09-01

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

  10. Mucosal vaccination by adenoviruses displaying reovirus sigma 1

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  11. Pharmacological Protection From Radiation ± Cisplatin-Induced Oral Mucositis

    International Nuclear Information System (INIS)

    Cotrim, Ana P.; Yoshikawa, Masanobu; Sunshine, Abraham N.; Zheng Changyu; Sowers, Anastasia L.; Thetford, Angela D.; Cook, John A.; Mitchell, James B.; Baum, Bruce J.

    2012-01-01

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

  12. Current practices for management of oral mucositis in cancer patients

    NARCIS (Netherlands)

    Raber-Durlacher, J. E.

    1999-01-01

    Many anticancer therapies induce oral mucositis, diminishing the patient's quality of life. Especially in neutropenic patients, it can lead to life-threatening systemic infection. Moreover, it can become a limiting factor in intensive treatment schedules. Many interventions are aimed at reducing

  13. Cellular and mucosal immune responses in the respiratory tract of ...

    African Journals Online (AJOL)

    Summary: This experiment was conducted to evaluate the cellular and mucosal responses in the respiratory tract of Nigerian goats vaccinated intranasally with recombinant Mannheimia hemolytica bacterine. Twenty one goats were divided into five groups, five goats each in three vaccinated groups while three goats each ...

  14. Management of chronic mucosal otitis media in children

    NARCIS (Netherlands)

    van der Veen, E.L.

    2010-01-01

    Chronic mucosal otitis media (COM) is one of the most common infectious diseases in children worldwide. As it causes considerable morbidity and is a major global cause of hearing impairment, establishing its most effective treatment is important. It is generally accepted that antibiotic eardrops

  15. Management of oral mucositis in patients with cancer.

    NARCIS (Netherlands)

    Stone, R.; Fliedner, M.C.; Smiet, A.C.M.

    2005-01-01

    Oral mucositis (OM) is a distressing toxic effect of chemotherapy and radiotherapy. It can increase the need for total parenteral nutrition and opioid analgesics, prolong hospital stays, increase the risk of infection, and greatly diminish a patient's quality of life. Nurses play a critical role in

  16. Neonatal Cytokine Profile in the Airway Mucosal Lining Fluid Is Skewed by Maternal Atopy

    DEFF Research Database (Denmark)

    Folsgaard, Nilofar V.; Chawes, Bo L.; Rasmussen, Morten A.

    2012-01-01

    on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. Objectives: To study parental atopic imprinting on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. Methods: Eighteen cytokines and chemokines were quantified in nasal mucosal...

  17. Oral Cryotherapy for Preventing Oral Mucositis in Patients Receiving Cancer Treatment.

    Science.gov (United States)

    Riley, Philip; McCabe, Martin G; Glenny, Anne-Marie

    2016-10-01

    In patients receiving treatment for cancer, does oral cryotherapy prevent oral mucositis? Oral cryotherapy is effective for the prevention of oral mucositis in adults receiving fluorouracil-based chemotherapy for solid cancers, and for the prevention of severe oral mucositis in adults receiving high-dose melphalan-based chemotherapy before hematopoietic stem cell transplantation (HSCT).

  18. Diverticulosis of colon: Case report

    International Nuclear Information System (INIS)

    Han, Chang Yul

    1972-01-01

    The authors reports 2 cases of diverticulosis involving the sacending colon and cecum: one, 55 year old, 85 kg Korean male admitted to Paik Hospital because of abdominal palm, constipation and tenderness in the right lower abdomen. The other, 48 year old, 78 kg male visited to our hospital for the routine examination. According to late European and American statistics, the colonic diverticulosis was discovered in late middle life about 20%, however, the incidence of colonic diverticulosis is rare in Korea. This paper presents a brief review of literature on the etiology, incidence and symptom

  19. Vasohibin-1 suppresses colon cancer

    Science.gov (United States)

    Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

    2015-01-01

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor. However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo. PMID:25797264

  20. Colonic motility in proctalgia fugax.

    Science.gov (United States)

    Harvey, R F

    1979-10-06

    Intraluminal pressure recordings were obtained from the rectum and sigmoid colon in two patients experiencing attacks of proctalgia fugax. In each patient the pain appeared to result from contractions of the sigmoid colon, and not from spasm of the levator ani, rectal wall muscle, or anal sphincters, all of which have previously been suggested as the source of such pain. Proctalgia fugax therefore appears, at least in some patients, to be an unusual variant of the irritable bowel syndrome, in which pain is referred from the sigmoid colon to the rectum.

  1. Vasohibin-1 suppresses colon cancer.

    Science.gov (United States)

    Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

    2015-04-10

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor.However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo.

  2. Oral and intestinal mucositis - causes and possible treatments.

    Science.gov (United States)

    Duncan, M; Grant, G

    2003-11-01

    Chemotherapy and radiotherapy, whilst highly effective in the treatment of neoplasia, can also cause damage to healthy tissue. In particular, the alimentary tract may be badly affected. Severe inflammation, lesioning and ulceration can occur. Patients may experience intense pain, nausea and gastro-enteritis. They are also highly susceptible to infection. The disorder (mucositis) is a dose-limiting toxicity of therapy and affects around 500 000 patients world-wide annually. Oral and intestinal mucositis is multi-factorial in nature. The disruption or loss of rapidly dividing epithelial progenitor cells is a trigger for the onset of the disorder. However, the actual dysfunction that manifests and its severity and duration are greatly influenced by changes in other cell populations, immune responses and the effects of oral/gut flora. This complexity has hampered the development of effective palliative or preventative measures. Recent studies have concentrated on the use of bioactive/growth factors, hormones or interleukins to modify epithelial metabolism and reduce the susceptibility of the tract to mucositis. Some of these treatments appear to have considerable potential and are at present under clinical evaluation. This overview deals with the cellular changes and host responses that may lead to the development of mucositis of the oral cavity and gastrointestinal tract, and the potential of existing and novel palliative measures to limit or prevent the disorder. Presently available treatments do not prevent mucositis, but can limit its severity if used in combination. Poor oral health and existing epithelial damage predispose patients to mucositis. The elimination of dental problems or the minimization of existing damage to the alimentary tract, prior to the commencement of therapy, lowers their susceptibility. Measures that reduce the flora of the tract, before therapy, can also be helpful. Increased production of free radicals and the induction of inflammation are

  3. Anti-inflammatory effects of the selective phosphodiesterase 3 inhibitor, cilostazol, and antioxidants, enzymatically-modified isoquercitrin and α-lipoic acid, reduce dextran sulphate sodium-induced colorectal mucosal injury in mice.

    Science.gov (United States)

    Kangawa, Yumi; Yoshida, Toshinori; Abe, Hajime; Seto, Yoshiki; Miyashita, Taishi; Nakamura, Michi; Kihara, Tohru; Hayashi, Shim-Mo; Shibutani, Makoto

    2017-04-04

    Developing effective treatments and preventing inflammatory bowel disease (IBD) are urgent challenges in improving patients' health. It has been suggested that platelet activation and reactive oxidative species generation are involved in the pathogenesis of IBD. We examined the inhibitory effects of a selective phosphodiesterase-3 inhibitor, cilostazol (CZ), and two antioxidants, enzymatically modified isoquercitrin (EMIQ) and α-lipoic acid (ALA), against dextran sulphate sodium (DSS)-induced colitis. BALB/c mice were treated with 0.3% CZ, 1.5% EMIQ, and 0.2% ALA in their feed. Colitis was induced by administering 5% DSS in drinking water for 8days. The inhibitory effects of these substances were evaluated by measuring relevant clinical symptoms (faecal blood, diarrhoea, and body weight loss), colon length, plasma cytokine and chemokine levels, whole genome gene expression, and histopathology. Diarrhoea was suppressed by each treatment, while CZ prevented shortening of the colon length. All treatment groups exhibited decreased plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α compared with the DSS group. Microarray analysis showed that cell adhesion, cytoskeleton regulation, cell proliferation, and apoptosis, which might be related to inflammatory cell infiltration and mucosal healing, were affected in all the groups. DSS-induced mucosal injuries such as mucosal loss, submucosal oedema, and inflammatory cell infiltration in the distal colon were prevented by CZ or antioxidant treatment. These results suggest that anti-inflammatory effects of these agents reduced DSS-induced mucosal injuries in mice and, therefore, may provide therapeutic benefits in IBD. Copyright © 2016 Elsevier GmbH. All rights reserved.

  4. Primary double contrast study of the colon with citrate-sorbitol-barium suspension in the diagnosis of chronic colitis

    International Nuclear Information System (INIS)

    Sidorov, V.S.

    1991-01-01

    X-ray investigation of the colon was conducted in 292 patients with clinically diagnosed chronic colitis: standard 3-phase irrigoscopy-in 189 patients and a primary double contrast study of the colon with citrate-sorbitol-barium suspenzion - in 103. Basing on X-ray and morphological findings, the diagnosis was confirmed in 128 patients of the 1st group (68.2 %) and in 89 patients of the 2nd group (86 %). The primary double contrast study of the colon was found more effective as it permitted the detection of elements of the mucosal microcontours: transversal strips, not coinciding with haustration, focal granularity, diffuse granularity, small barium suspension depots or niches, nodular granularity. It permitted the recommendation of the method for a wide clinical use

  5. Mucosal healing and deep remission: What does it mean?

    Science.gov (United States)

    Rogler, Gerhard; Vavricka, Stephan; Schoepfer, Alain; Lakatos, Peter L

    2013-01-01

    The use of specific terms under different meanings and varying definitions has always been a source of confusion in science. When we point our efforts towards an evidence based medicine for inflammatory bowel diseases (IBD) the same is true: Terms such as “mucosal healing” or “deep remission” as endpoints in clinical trials or treatment goals in daily patient care may contribute to misconceptions if meanings change over time or definitions are altered. It appears to be useful to first have a look at the development of terms and their definitions, to assess their intrinsic and context-independent problems and then to analyze the different relevance in present-day clinical studies and trials. The purpose of such an attempt would be to gain clearer insights into the true impact of the clinical findings behind the terms. It may also lead to a better defined use of those terms for future studies. The terms “mucosal healing” and “deep remission” have been introduced in recent years as new therapeutic targets in the treatment of IBD patients. Several clinical trials, cohort studies or inception cohorts provided data that the long term disease course is better, when mucosal healing is achieved. However, it is still unclear whether continued or increased therapeutic measures will aid or improve mucosal healing for patients in clinical remission. Clinical trials are under way to answer this question. Attention should be paid to clearly address what levels of IBD activity are looked at. In the present review article authors aim to summarize the current evidence available on mucosal healing and deep remission and try to highlight their value and position in the everyday decision making for gastroenterologists. PMID:24282345

  6. Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice

    Science.gov (United States)

    Pineton de Chambrun, G; Body-Malapel, M; Frey-Wagner, I; Djouina, M; Deknuydt, F; Atrott, K; Esquerre, N; Altare, F; Neut, C; Arrieta, M C; Kanneganti, T-D; Rogler, G; Colombel, J-F; Cortot, A; Desreumaux, P; Vignal, C

    2014-01-01

    The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10−/−) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor. PMID:24129165

  7. Low residual diet and hydration improving double contrast examination of the colon

    International Nuclear Information System (INIS)

    Virkki, R.; Maekelae, P.

    1983-01-01

    Light food diet and low residual diet with hydration, both combined with Proctosal and Bisacodyl cleansing, were compared in 268 patients in the preparation of the colon for double contrast examination. Low residual diet with hydration resulted in significantly less residual fecal material, no flocculation of the barium coating and significantly denser mucosal coating. The examination had to be repeated more often (8.6%) after light food diet than after low residual diet with hydration (1.7%), but there was no statistically significant difference in the diagnostic accuracy. The hydration is important in avoiding patient discomforts and flocculation of the barium coating. Despite the use of laxatives, a strict diet restriction is needed to obtain consistently clean colon. (orig.)

  8. 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...

  9. Crohn's disease of the colon: ultrastructural changes in submuscular interstitial cells of Cajal

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johs.; Vanderwinden, Jean-Marie; Horn, Thomas

    2011-01-01

    of the submuscular plexus were often empty and dilated. Fibroblast-like cells selectively encased macrophages and mast cells. The cytological changes in ICC-SMP in CD are thus similar to changes seen in ulcerative colitis and may be of pathophysiological significance with regard to the motility and sensory......Interstitial cells of Cajal (ICC) at the submuscular border of the human colon (ICC-SMP) are the proposed pacemaker cells of the musculature. In patients with Crohn's disease (CD) of the colon, ICC-SMP showed characteristic cytological changes from controls. The changes comprised secondary...... lysosomes in connection with lipid droplets and cytoplasmic vacuoles or multiple empty, confluent and often outbulging vacuoles merging with cisterns of granular endoplasmic reticulum and clusters of glycogen granules. These changes were most pronounced in patients with macroscopical mucosal inflammation...

  10. The effect of parenteral immunisation on antibody production in the pig colon.

    Science.gov (United States)

    Rees, A S; Lysons, R J; Stokes, C R; Bourne, F J

    1989-11-30

    Local and systemic antibody production was studied in pigs to compare responses to live and killed bacterial antigen and purified protein antigen, with and without prior mucosal stimulation. Recovery from challenge with live bacteria and intramuscular injection with killed bacteria gave rise to similar high levels of serum IgG antibody, but the ratio of specific IgA to IgG in the colon was significantly higher after infection than following vaccination with killed bacteria. Vaccination with a protein antigen gave rise to serum and local antibody production. Prior feeding of the antigen had a tolerising effect on the serum antibody response, but production of IgG and IgA antibody by the colon was not suppressed.

  11. Colonization and environment

    International Nuclear Information System (INIS)

    Garcia Gutierrez, E.

    1999-01-01

    It stands out the man's paper in the deterioration of the soil and in the phenomenon of the desertization, the conflicts of the use of the soil in the country and the underestimate that it is made of this resource in the environmental analysis. The man's relationships are discussed with the earth and the problem of the soils of the Colombian Orinoquia is examined in terms of the excess of toxic elements as To the, Fe and Mn and the other elements like P, S, Ca, Mg, K, B, and Zn. It is examined the degradation and poverty of the organic complex of the soil, the physical degradation and chemistry and their susceptibility to the erosion, as well as the excess conditions and deficit of humidity. It is recognized that it lacks calibration of the analytic methods for the soils oxisoils of the Orinoquia and the Amazonia. The importance of the soils of the humid tropic is stood out as seat of colonization that have failed when not having an appropriate technology for its handling that it forces to undertake systems of migratory agriculture and to the transformation of the forest in prairie, phenomenon that comes accompanied by the degradation of the soils, illicit cultivations, social conflicts and alteration of the essential ecological processes for the survival

  12. Multidetector CT of the colon

    International Nuclear Information System (INIS)

    Luboldt, W.; Hoepffner, N.; Holzer, K.

    2003-01-01

    Multidetector technology, enabling faster imaging, higher spatial resolution and reduction in radiation dose, increases the role of CT in colonic diagnostic. The higher spatial resolution in the z-direction also changes the way to analyze the images. Instead of reading axial sections, now the colon can be systematically assessed in 3D by scrolling through multiplanar reconstructions or in CT colonography by virtual endoscopy. With ongoing improvements in computer-aided diagnosis CT colonography becomes an alternative to fiberoptic colonocopy for screening (http://www.multiorganscreening.org). In this article we propose a CT examination protocol for the colon, describe the typical imaging findings of different colonic diseases, and summarize the current status of CT colonography. (orig.)

  13. Understanding your colon cancer risk

    Science.gov (United States)

    ... for women and 2 drinks per day for men DO NOT smoke You can also have genetic testing done to assess your risk for colon cancer. If you have a strong family history of the disease, talk with your ...

  14. Colon Cleansing: Health or Hype?

    Science.gov (United States)

    ... cramps Dizziness Dehydration Bowel perforation Infection Depletion of probiotics, sodium and potassium Kidney damage Plus, colon cleansing ... goodbye to bacon, sausage, deli meats and hot dogs. Cancer-causing substances form when meats are preserved. ...

  15. Primary closure in colon trauma.

    Science.gov (United States)

    Salinas-Aragón, Luis Enrique; Guevara-Torres, Lorenzo; Vaca-Pérez, Enrique; Belmares-Taboada, Jaime Arístides; Ortiz-Castillo, Fátima de Guadalupe; Sánchez-Aguilar, Martín

    2009-01-01

    Primary repair of colon injuries is an accepted therapeutic option; however, controversy persists regarding its safety. Our objective was to report the evolution and presence of complications in patients with colon injury who underwent primary closure and to determine if the time interval (>6 h), degree of injury, contamination, anatomic site injured, PATI (Penetrating Abdominal Trauma Index) >25, and the presence of other injuries in colon trauma are associated with increased morbidity and mortality. This was a prospective, observational, longitudinal and descriptive study conducted at the Central Hospital "Dr. Ignacio Morones Prieto," San Luis Potosí, Mexico, from January 1, 2003 to December 31, 2007. We included patients with abdominal trauma with colon injury subjected to surgical treatment. chi(2) was used for basic statistical analysis. There were 481 patients with abdominal trauma who underwent surgery; 77(16.1%) had colon injury. Ninety percent (n = 69) were treated in the first 6 h; 91% (n = 70) were due to penetrating injuries, and gunshot wound accounted for 48% (n = 37). Transverse colon was the most frequently injured (38%) (n = 29). Grade I and II injuries accounted for 75.3% (n = 58). Procedures included primary repair (76.66 %) (n = 46); resection with anastomosis (8.3%) (n = 5); and colostomy (15%) (n = 9). Associated injuries were present in 76.6% (n = 59). There was some degree of contamination in 85.7% (n = 66); 82.8% (58) had PATI colon injury. Primary repair is a safe procedure for treatment of colon injuries. Patients with primary repair had lower morbidity (p <0.009). Surgery during the first 6 h (p <0.006) and in hemodynamically stable patients (p <0.014) had a lower risk of complications.

  16. M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.

    Science.gov (United States)

    Ye, Ting; Yue, Yan; Fan, Xiangmei; Dong, Chunsheng; Xu, Wei; Xiong, Sidong

    2014-07-31

    Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 μg pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Small invasive colon cancer with systemic metastasis: A case report

    Directory of Open Access Journals (Sweden)

    Sakamoto Taku

    2011-05-01

    Full Text Available ABSTRACT Background Recently, especially in Japan, several researchers have suggested that colorectal cancer can develop not only through an adenoma-carcinoma sequence but also from normal mucosa via a de novo pathway, and that these de novo cancers have more aggressive malignant potential. We report a case of aggressive colon cancer resulting in systemic metastasis despite small tumour size. Case Presentation A 35-year-old woman presented at the referring hospital with swelling of the left cervical lymph node. Biopsy of the lymph node revealed metastatic adenocarcinoma; however, CT scan and mammography were unable to identify the site of the primary lesion. She was diagnosed with unknown primary cancer and referred to our hospital for further examination. Immunohistochemical reevaluation showed the cervical lymph node biopsy specimen to be positive for CDX2 and CK20 and negative for CK7 expression, leading us to suspect the presence of a primary colorectal cancer. We performed a total colonoscopy, and detected a small protruding lesion in the transverse colon. The tumour was only 12 mm in diameter, with a central depressed component and a severely thickened stalk, which suggested direct cancer invasion of the deep submucosa. We concluded that this lesion was the site of origin of the metastasis despite the small tumour size, and performed diagnostic endoscopic mucosal resection. The lesion was found to have an intramucosal cancer component, demonstrating that this lesion represented primary colon cancer. The patient was referred to the gastrointestinal oncology division for systemic chemotherapy. Conclusions In this case, immunohistochemical findings strongly suggested the existence of a colorectal cancer. The non-polypoid gross appearance of the tumour suggested that it can originate de novo , thus providing a valuable case in support of the aggressive malignant potential of a de novo colorectal cancer pathway.

  18. Colon in acute intestinal infection.

    Science.gov (United States)

    Guarino, Alfredo; Buccigrossi, Vittoria; Armellino, Carla

    2009-04-01

    The colon is actively implicated in intestinal infections not only as a target of enteric pathogens and their products but also as a target organ for treatment. In the presence of diarrhea, both of osmotic and secretory nature, the colon reacts with homeostatic mechanisms to increase ion absorption. These mechanisms can be effectively exploited to decrease fluid discharge. A model of intestinal infections using rotavirus (RV) in colonic cells was set up and used to define a dual model of secretory and osmotic diarrhea in sequence. Using this model, antidiarrheal drugs were tested, namely zinc and the enkephalinase inhibitor racecadotril. Zinc was able to decrease the enterotoxic activity responsible for secretory diarrhea. It also inhibited the cytotoxic effect of RV. The mechanism of zinc was related at least in part to the activation of MAPK activity, but also a direct antiviral effect was observed. Racecadotril showed a potent and selective inhibition of active secretion, being particularly effective in the first phase of RV diarrhea. The use of drugs active at the colonic level, therefore, offers effective options to treat intestinal infections in childhood. In addition, the colon is the natural site of colonic microflora, a target of probiotic therapy, which is the first line of approach recommended by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition to treat infectious diarrhea.

  19. L-arginine and glycine supplementation in the repair of the irradiated colonic wall of rats.

    Science.gov (United States)

    de Aguiar Picanço, Etiene; Lopes-Paulo, Francisco; Marques, Ruy G; Diestel, Cristina F; Caetano, Carlos Eduardo R; de Souza, Mônica Vieira Mano; Moscoso, Gabriela Mendes; Pazos, Helena Maria F

    2011-05-01

    Radiotherapy is widely used for cancer treatment but has harmful effects. This study aimed to assess the effects of L-arginine and glycine supplementation on the colon wall of rats submitted to abdominal irradiation. Forty male Wistar rats were randomly divided into four groups: I-healthy, II-irradiated with no amino acid supplementation, III-irradiated and supplemented with L-arginine, and IV-irradiated and supplemented with glycine. The animals received supplementation for 14 days, with irradiation being applied on the eighth day of the experiment. All animals underwent laparotomy on the 15th day for resection of a colonic segment for stereologic analysis. Parametric and nonparametric tests were used for statistical analysis, with the level of significance set at p ≤0.05. Stereologic analysis showed that irradiation induced a reduction of the total volume of the colon wall of group II and III animals compared to healthy controls, but not of group IV animals supplemented with glycine. The mucosal layer of the irradiated animals of all groups was reduced compared to healthy group I animals, but supplementation with L-arginine and glycine was effective in maintaining the epithelial surface of the mucosal layer. The present results suggest that glycine supplementation had a superior effect on the irradiated colon wall compared to L-arginine supplementation since it was able to maintain the thickness of the wall and the epithelial surface of the mucosa, whereas L-arginine maintained the partial volume of the epithelium and the epithelial surface, but not the total volume of the intestinal wall.

  20. Exploring the chemotactic attraction of Campylobacter jejuni in chicken colonization

    DEFF Research Database (Denmark)

    Vegge, Christina Skovgaard; Brøndsted, Lone; Ingmer, Hanne

    Campylobacter jejuni is the primary food borne bacterial pathogen in the developed world. The most important reservoir for C. jejuni is the gut of chickens, which are colonized commensally and efficiently by this organism. Predominantly the mucus filled crypts of the lower gastrointestinal tract....... These mutants will be analyzed for their chemotatic capacity in order to investigate the chemoreceptor function and to identify matching chemoeffectors. Furthermore, selected mutants will be investigated for their ability to colonize chickens with focus on establishment, level, and persistence. Special emphasis...

  1. Colonic diverticulosis is not a risk factor for colonic adenoma.

    Science.gov (United States)

    Hong, Wandong; Dong, Lemei; Zippi, Maddalena; Stock, Simon; Geng, Wujun; Xu, Chunfang; Zhou, Mengtao

    2018-01-01

    Colonic diverticulosis may represent a risk factor for colonic adenomas by virtue of the fact that evolving data suggest that these 2 conditions may share common risk factors such as Western dietary pattern and physical inactivity. This study aims to investigate the association between colonic diverticulosis and colonic adenomas in mainland China. We conducted a cross-sectional study on patients who underwent colonoscopic examination between October 2013 and December 2014 in a university hospital in mainland China. Age, gender, colonic adenomas, advanced adenomas, and distribution of diverticulosis were recorded during the procedures. Multivariate logistic regression and stratified analysis were used to evaluate the associations between the prevalence of diverticulosis and age, sex, and presence of colonic adenomas and advanced adenomas. A total of 17,456 subjects were enrolled. The prevalence of colonic diverticulosis and adenoma was 2.4% and 13.2%, respectively. With regard to distribution of diverticula, most (365/424, 86.1%) were right-sided. Multiple logistic regression analysis suggested that age and male gender were independent risk factors for adenoma and advanced adenoma. There was no relationship between diverticulosis or location of diverticulosis and presence of adenoma and advanced adenoma adjusting by age and gender. In a stratified analysis according to age and gender, similar results were also noted. There was no statistical relationship between diverticulosis and the risk of adenoma and advanced adenoma. Our results may not be generalized to the Western population due to the fact that left-sided diverticular cases were very small in our study.

  2. Operative factors associated with short-term outcome in horses with large colon volvulus: 47 cases from 2006 to 2013.

    Science.gov (United States)

    Gonzalez, L M; Fogle, C A; Baker, W T; Hughes, F E; Law, J M; Motsinger-Reif, A A; Blikslager, A T

    2015-05-01

    There is an important need for objective parameters that accurately predict the outcome of horses with large colon volvulus. To evaluate the predictive value of a series of histomorphometric parameters on short-term outcome, as well as the impact of colonic resection on horses with large colon volvulus. Retrospective cohort study. Adult horses admitted to the Equine and Farm Animal Veterinary Center at North Carolina State University, Peterson and Smith and Chino Valley Equine Hospitals between 2006 and 2013 that underwent an exploratory coeliotomy, diagnosed with large colon volvulus of ≥360 degrees, where a pelvic flexure biopsy was obtained, and that recovered from general anaesthesia, were selected for inclusion in the study. Logistic regression was used to determine associations between signalment, histomorphometric measurements of interstitium-to-crypt ratio, degree of haemorrhage, percentage loss of luminal and glandular epithelium, as well as colonic resection with short-term outcome (discharge from the hospital). Pelvic flexure biopsies from 47 horses with large colon volvulus were evaluated. Factors that were significantly associated with short-term outcome on univariate logistic regression were Thoroughbred breed (P = 0.04), interstitium-to-crypt ratio >1 (P = 0.02) and haemorrhage score ≥3 (P = 0.005). Resection (P = 0.92) was not found to be associated significantly with short-term outcome. No combined factors increased the likelihood of death in forward stepwise logistic regression modelling. A digitally quantified measurement of haemorrhage area strengthened the association of haemorrhage with nonsurvival in cases of large colon volvulus. Histomorphometric measurements of interstitium-to-crypt ratio and degree of haemorrhage predict short-term outcome in cases of large colon volvulus. Resection was not associated with short-term outcome in horses selected for this study. Accurate quantification of mucosal haemorrhage at the time of surgery may

  3. Induction of systemic and mucosal immunity against methicillin-resistant Staphylococcus aureus infection by a novel nanoemulsion adjuvant vaccine

    Directory of Open Access Journals (Sweden)

    Sun HW

    2015-12-01

    Full Text Available HongWu Sun,1,* Chao Wei,1,* BaoShuai Liu,1 HaiMing Jing,1 Qiang Feng,2 YaNan Tong,1 Yun Yang,1 LiuYang Yang,1 QianFei Zuo,1 Yi Zhang,1 QuanMing Zou,1 Hao Zeng1 1National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University of Chinese PLA, 2Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, People’s Republic of China *These authors contributed equally to this work Abstract: The Gram-positive bacterial pathogen methicillin-resistant Staphylococcus aureus (MRSA can cause infections in the bloodstream, endocardial tissue, respiratory tract, culture-confirmed skin, or soft tissue. There are currently no effective vaccines, and none are expected to become available in the near future. An effective vaccine capable of eliciting both systemic and mucosal immune responses is also urgently needed. Here, we reported a novel oil-in-water nanoemulsion adjuvant vaccine containing an MRSA recombination protein antigen, Cremophor EL-35® as a surfactant, and propylene glycol as a co-surfactant. This nanoemulsion vaccine, whose average diameter was 31.34±0.49 nm, demonstrated good protein structure integrity, protein specificity, and good stability at room temperature for 1 year. The intramuscular systemic and nasal mucosal immune responses demonstrated that this nanoemulsion vaccine could improve the specific immune responses of immunoglobulin (IgG and related subclasses, such as IgG1, IgG2a, and IgG2b, as well as IgA, in the serum after Balb/c mice intramuscular immunization and C57 mice nasal immunization. Furthermore, this nanoemulsion vaccine also markedly enhanced the interferon-γ and interleukin-17A cytokine cell immune response, improved the survival ratio, and reduced bacterial colonization. Taken together, our results show that this novel nanoemulsion vaccine has great potential and is a

  4. Concurrent colonic mucosa-associated lymphoid tissue lymphoma and adenoma diagnosed after a positive fecal occult blood test: a case report.

    Science.gov (United States)

    Lin, Pei-Chiang; Chen, Jinn-Shiun; Deng, Po; Wang, Chih-Wei; Huang, Chiung-Huei; Tang, Reiping; Chiang, Jy-Ming; Yeh, Chien-Yuh; Hsieh, Pao-Shiu; Tsai, Wen-Sy; Chiang, Sum-Fu

    2016-01-27

    Colonic lymphoma is an uncommon presentation of extranodal lymphoma. Colonic mucosa-associated lymphoid tissue lymphoma is a different entity from gastric mucosa-associated lymphoid tissue lymphoma, and very rare. The presentation and management of colonic mucosa-associated lymphoid tissue are highly variable in the literature. We report the case of a 59-year-old Taiwanese man who underwent a colonoscopy after a positive test for fecal occult blood. His past history included hypertension and hyperthyroidism. The colonoscopy revealed an adenomatous polyp and mucosa-associated lymphoid tissue lymphoma. We successfully performed a polypectomy and endoscopic mucosal resection. The lymphoma was staged according to the Ann Arbor system modified by Musshoff as E-I. Our patient showed no lymphoma recurrence over a 3-year follow-up. Endoscopic mucosal resection for colonic mucosa-associated lymphoid tissue lymphoma without disseminated disease may be feasible. We successfully used colonoscopic treatment without adjuvant therapy to treat early-stage pathogen-free colonic mucosa-associated lymphoid tissue lymphoma.

  5. Mucosal versus muscle pain sensitivity in provoked vestibulodynia

    Directory of Open Access Journals (Sweden)

    Witzeman K

    2015-08-01

    Full Text Available Kathryn Witzeman,1 Ruby HN Nguyen,2 Alisa Eanes,3 Sawsan As-Sanie,4 Denniz Zolnoun51Department of Obstetrics and Gynecology, Denver Health Medical Center, Denver, CO, 2Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, 3Pelvic Pain Research Unit, Division of Advanced Laparoscopy and Pelvic Pain, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC, 4Department of Obstetrics and Gynecology, Division of Minimally Invasive Gynecologic Surgery, University of Michigan, Ann Arbor, MI, 5Department of Obstetrics and Gynecology and Center for Neurosensory Disorders, University of North Carolina, Chapel Hill, NC, USABackground: An estimated 8.3%–16% of women experience vulvovaginal discomfort during their lifetime. Frequently these patients report provoked pain on contact or with attempted intercourse, commonly referred to as provoked vestibulodynia (PVD. Despite the burden of this condition, little is known about its potential etiologies including pelvic floor muscular dysfunction and mucosal components. This knowledge would be beneficial in developing targeted therapies including physical therapy.Objective: To explore the relative contribution of mucosal versus muscle pain sensitivity on pain report from intercourse among women with PVD.Design: In this proof of concept study, 54 women with PVD underwent a structured examination assessing mucosal and pelvic muscle sensitivity.Methods: We examined three mucosal sites in the upper and lower vestibule. Patients were asked to rate their pain on cotton swab palpation of the mucosa using a 10-point visual analog scale. Muscle pain was assessed using transvaginal application of pressure on right and left puborectalis, and the perineal muscle complex. The Gracely pain scale (0–100 was used to assess the severity of pain with intercourse, with women rating the lowest, average, and highest pain levels; a 100 rating the

  6. Colonization and environment

    International Nuclear Information System (INIS)

    Garcia Gutierrez, E.

    1999-01-01

    The environmental results of the colonization, process and their consequences are analyzed in the local, national and international order, the activities through which the acts on the means and the nature of these. It is examined the meaning of the sustainable development, the phenomenon of the exhaustion of the ecosystems and their responsible ones. It discusses the importance of the Orinoquia in the mark of the environmental problems in the international order, the region has been intensely exploded by means of intensive production systems, what has led to the exhaustion of these areas in the world environment. The colonist's paper is exposed in the environmental deterioration, in front of the function of the tropical humid forest and it confirms a focus that it approaches the environmental problem from a perspective that makes emphasis in the social component of that problem, in opposition to the conservators where the ecosystem is the only valid reason and the social groups that intervene him, they should simply disappear. It is necessary the necessity to focus of integral way, the colonist's nature like element of a social group, the list that completes in the mark of the nation and their development model, the political economic system and the nationality inside which makes their economic decisions and of production. It is recognized that they are not enough solutions of technical order to impact on the use and sustainable handling of the Orinoquia, but rather it should be contemplated the economic, social, environmental and political aspects of the problem simultaneously, as well as the growing and resolved participation of the social group in their group

  7. Loss of claudin-3 expression induces IL6/gp130/Stat3 signaling to promote colon cancer malignancy by hyperactivating Wnt/β-catenin signaling.

    Science.gov (United States)

    Ahmad, R; Kumar, B; Chen, Z; Chen, X; Müller, D; Lele, S M; Washington, M K; Batra, S K; Dhawan, P; Singh, A B

    2017-11-23

    The hyperactivated Wnt/β-catenin signaling acts as a switch to induce epithelial to mesenchymal transition and promote colorectal cancer. However, due to its essential role in gut homeostasis, therapeutic targeting of this pathway has proven challenging. Additionally, IL-6/Stat-3 signaling, activated by microbial translocation through the dysregulated mucosal barrier in colon adenomas, facilitates the adenoma to adenocarcinomas transition. However, inter-dependence between these signaling pathways and key mucosal barrier components in regulating colon tumorigenesis and cancer progression remains unclear. In current study, we have discovered, using a comprehensive investigative regimen, a novel and tissue-specific role of claudin-3, a tight junction integral protein, in inhibiting colon cancer progression by serving as the common rheostat of Stat-3 and Wnt-signaling activation. Loss of claudin-3 also predicted poor patient survival. These findings however contrasted an upregulated claudin-3 expression in other cancer types and implicated role of the epigenetic regulation. Claudin-3-/- mice revealed dedifferentiated and leaky colonic epithelium, and developed invasive adenocarcinoma when subjected to colon cancer. Wnt-signaling hyperactivation, albeit in GSK-3β independent manner, differentiated colon cancer in claudin-3-/- mice versus WT-mice. Claudin-3 loss also upregulated the gp130/IL6/Stat3 signaling in colonic epithelium potentially assisted by infiltrating immune components. Genetic and pharmacological studies confirmed that claudin-3 loss induces Wnt/β-catenin activation, which is further exacerbated by Stat-3-activation and help promote colon cancer. Overall, these novel findings identify claudin-3 as a therapeutic target for inhibiting overactivation of Wnt-signaling to prevent CRC malignancy.

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

    International Nuclear Information System (INIS)

    Epstein, J.B.; Wong, F.L.W.

    1994-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-02-01

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

  10. Oral mucositis in head and neck cancer: risk, biology, and management.

    Science.gov (United States)

    Sonis, Stephen T

    2013-01-01

    Of the toxicities associated with conventional forms of treatment for head and neck cancers, probably none has such a consistent legacy as oral mucositis.1 Despite the fact that mucosal injury was noted as far back as Marie Curie's first forays into therapeutic radiation, an effective intervention has yet to be developed. In addition to its historic link to radiation, new therapeutic strategies including induction chemotherapy often produce mucositis, and targeted therapies appear to alter mucositis risk and its severity and course.2 The symptomatic effect of oral mucositis is profound. Disabling oral and oropharyngeal pain prevents patients from eating normally, requires opiate analgesics, and in some cases results in alteration or discontinuation of anticancer therapy.3 Furthermore, the health and economic consequences of oral mucositis are far from trivial. The incremental cost of oral mucositis in patients with head and neck cancer exceeds $17,000 (USD).4.

  11. Perspectives toward oral mucositis prevention from parents and health care professionals in pediatric cancer.

    Science.gov (United States)

    Ethier, Marie-Chantal; Regier, Dean A; Tomlinson, Deborah; Judd, Peter; Doyle, John; Gassas, Adam; Naqvi, Ahmed; Sung, Lillian

    2012-08-01

    The objectives of this study were: (1) to describe parents and health care professionals (HCPs) perceived importance of oral mucositis prevention in children with cancer; (2) To describe utilities and willingness-to-pay (WTP) to prevent mucositis. Respondents included parents of children receiving intensive chemotherapy for leukemia/lymphoma or undergoing stem cell transplantation and HCPs caring for children with cancer. Importance of mild and severe oral mucositis was estimated using a visual analogue scale (VAS). Mucositis-associated utilities were elicited using the time trade-off technique (TTO). WTP to avoid mucositis was obtained using contingent valuation. These techniques quantify how much time or money the participant is willing to relinquish in order to prevent mucositis. Eighty-two parents and 60 HCPs were included. Parents and HCPs believed mild mucositis to be of similar importance (median VAS 2.5 versus 3.6; P = 0.357) while parents considered severe mucositis less important than HCPs (median VAS 8.3 versus 9.0; P parent versus HCP responses were seen with TTO (mild or severe mucositis) and most parents were not willing to trade any survival time to prevent severe mucositis. Parents were willing to pay significantly more than HCPs to prevent mild mucositis (average median WTP $1,371 CAN vs. $684 CAN, P = 0.031). No differences were seen in WTP to prevent severe mucositis. Parents and HCP believe severe mucositis to be important, although it is more important to HCPs. Parents would not be willing to reduce life expectancy to eliminate mucositis.

  12. Novel engineered systems for oral, mucosal and transdermal drug delivery.

    Science.gov (United States)

    Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

    2013-08-01

    Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

  13. Intestinal stromal cells in mucosal immunity and homeostasis.

    Science.gov (United States)

    Owens, B M J; Simmons, A

    2013-03-01

    A growing body of evidence suggests that non-hematopoietic stromal cells of the intestine have multiple roles in immune responses and inflammation at this mucosal site. Despite this, many still consider gut stromal cells as passive structural entities, with past research focused heavily on their roles in fibrosis, tumor progression, and wound healing, rather than their contributions to immune function. In this review, we discuss our current knowledge of stromal cells in intestinal immunity, highlighting the many immunological axes in which stromal cells have a functional role. We also consider emerging data that broaden the potential scope of their contribution to immunity in the gut and argue that these so-called "non-immune" cells are reclassified in light of their diverse contributions to intestinal innate immunity and the maintenance of mucosal homeostasis.

  14. Effect of bupivacaine lozenges on oral mucositis pain

    DEFF Research Database (Denmark)

    Mogensen, Stine; Treldal, Charlotte; Kristensen, Claus A

    2017-01-01

    Introduction: A nonblinded parallel-group randomized controlled study investigated the efficacy and tolerability of repeated administration of a bupivacaine lozenge (25 mg) as pain management for oral mucositis pain in head and neck cancer patients as add-on to standard systemic pain management...... with bupivacaine lozenges (taken up to every 2 hours) plus standard pain treatment minus topical lidocaine (Lozenge group) or standard pain treatment including topical lidocaine (Control group). The efficacy analysis included 38 patients, as 12 patients were excluded because of changes in study design and missing...... that the bupivacaine lozenge as an add-on to standard pain treatment had a clinically significant pain-relieving effect in patients with oral mucositis. ClinicalTrialsgov: NCT02252926....

  15. Mucosal immunity in the female genital tract, HIV/AIDS.

    Science.gov (United States)

    Reis Machado, Juliana; da Silva, Marcos Vinícius; Cavellani, Camila Lourencini; dos Reis, Marlene Antônia; Monteiro, Maria Luiza Gonçalves dos Reis; Teixeira, Vicente de Paula Antunes; Miranda Corrêa, Rosana Rosa

    2014-01-01

    Mucosal immunity consists of innate and adaptive immune responses which can be influenced by systemic immunity. Despite having been the subject of intensive studies, it is not fully elucidated what exactly occurs after HIV contact with the female genital tract mucosa. The sexual route is the main route of HIV transmission, with an increased risk of infection in women compared to men. Several characteristics of the female genital tract make it suitable for inoculation, establishment of infection, and systemic spread of the virus, which causes local changes that may favor the development of infections by other pathogens, often called sexually transmitted diseases (STDs). The relationship of these STDs with HIV infection has been widely studied. Here we review the characteristics of mucosal immunity of the female genital tract, its alterations due to HIV/AIDS, and the characteristics of coinfections between HIV/AIDS and the most prevalent STDs.

  16. Influence of bedding type on mucosal immune responses.

    Science.gov (United States)

    Sanford, Amy N; Clark, Stephanie E; Talham, Gwen; Sidelsky, Michael G; Coffin, Susan E

    2002-10-01

    The mucosal immune system interacts with the external environment. In the study reported here, we found that bedding materials can influence the intestinal immune responses of mice. We observed that mice housed on wood, compared with cotton bedding, had increased numbers of Peyer's patches (PP) visible under a dissecting microscope. In addition, culture of lymphoid organs revealed increased production of total and virus-specific IgA by PP and mesenteric lymph node (MLN) lymphocytes from mice housed on wood, compared with cotton bedding. However, bedding type did not influence serum virus-specific antibody responses. These observations indicate that bedding type influences the intestinal immune system and suggest that this issue should be considered by mucosal immunologists and personnel at animal care facilities.

  17. Inactivation of Adenomatous Polyposis Coli Reduces Bile Acid/Farnesoid X Receptor Expression through Fxr gene CpG Methylation in Mouse Colon Tumors and Human Colon Cancer Cells.

    Science.gov (United States)

    Selmin, Ornella I; Fang, Changming; Lyon, Adam M; Doetschman, Tom C; Thompson, Patricia A; Martinez, Jesse D; Smith, Jeffrey W; Lance, Peter M; Romagnolo, Donato F

    2016-02-01

    The farnesoid X receptor (FXR) regulates bile acid (BA) metabolism and possesses tumor suppressor functions. FXR expression is reduced in colorectal tumors of subjects carrying inactivated adenomatous polyposis coli (APC). Identifying the mechanisms responsible for this reduction may offer new molecular targets for colon cancer prevention. We investigated how APC inactivation influences the regulation of FXR expression in colonic mucosal cells. We hypothesized that APC inactivation would epigenetically repress nuclear receptor subfamily 1, group H, member 4 (FXR gene name) expression through increased CpG methylation. Normal proximal colonic mucosa and normal-appearing adjacent colonic mucosa and colon tumors were collected from wild-type C57BL/6J and Apc-deficient (Apc(Min) (/+)) male mice, respectively. The expression of Fxr, ileal bile acid-binding protein (Ibabp), small heterodimer partner (Shp), and cyclooxygenase-2 (Cox-2) were determined by real-time polymerase chain reaction. In both normal and adjacent colonic mucosa and colon tumors, we measured CpG methylation of Fxr in bisulfonated genomic DNA. In vitro, we measured the impact of APC inactivation and deoxycholic acid (DCA) treatment on FXR expression in human colon cancer HCT-116 cells transfected with silencing RNA for APC and HT-29 cells carrying inactivated APC. In Apc(Min) (/+) mice, constitutive CpG methylation of the Fxrα3/4 promoter was linked to reduced (60-90%) baseline Fxr, Ibabp, and Shp and increased Cox-2 expression in apparently normal adjacent mucosa and colon tumors. Apc knockdown in HCT-116 cells increased cellular myelocytomatosis (c-MYC) and lowered (∼50%) FXR expression, which was further reduced (∼80%) by DCA. In human HCT-116 but not HT-29 colon cancer cells, DCA induced FXR expression and lowered CpG methylation of FXR. We conclude that the loss of APC function favors the silencing of FXR expression through CpG hypermethylation in mouse colonic mucosa and human colon cells

  18. Injury and mechanism of recombinant E. coli expressing STa on piglets colon.

    Science.gov (United States)

    Lv, Yang; Li, Xueni; Zhang, Lin; Shi, Yutao; DU, Linxiao; Ding, Binying; Hou, Yongqing; Gong, Joshua; Wu, Tao

    2018-02-09

    Enterotoxigenic Escherichia coli (ETEC) is primary pathogenic bacteria of piglet diarrhea, over two thirds of piglets diarrhea caused by ETEC are resulted from STa-producing ETEC strains. This experiment was conducted to construct the recombinant E. coli expressing STa and study the injury and mechanism of recombinant E. coli expressing STa on 7 days old piglets colon. Twenty-four 7 days old piglets were allotted to four treatments: control group, STa group (2 × 10 9 CFU E. coli LMG194-STa), LMG194 group (2 × 10 9 CFU E. coli LMG194) and K88 group (2 × 10 9 CFU E. coli K88). The result showed that E. coli infection significantly increased diarrhea rates; changed DAO activity in plasma and colon; damaged colonic mucosal morphology including crypt depth, number of globet cells, density of lymphocytes and lamina propria cell density; substantially reduced antioxidant capacity by altering activities of GSH-Px, SOD, and TNOS and productions of MDA and H 2 O 2 ; obviously decreased AQP3, AQP4 and KCNJ13 protein expression levels; substantially altered the gene expression levels of inflammatory cytokines. Conclusively, STa group had the biggest effect on these indices in four treatment groups. These results suggested that the recombinant strain expressed STa can induce piglets diarrhea and colonic morphological and funtional damage by altering expression of proteins connect to transportation function and genes associated with intestinal injury and inflammatory cytokines.

  19. Knife-assisted snare resection: a novel technique for resection of scarred polyps in the colon.

    Science.gov (United States)

    Chedgy, Fergus J Q; Bhattacharyya, Rupam; Kandiah, Kesavan; Longcroft-Wheaton, Gaius; Bhandari, Pradeep

    2016-03-01

    There have been significant advances in the management of complex colorectal polyps. Previous failed resection or polyp recurrence is associated with significant fibrosis, making endoscopic resection extremely challenging; the traditional approach to these lesions is surgery. The aim of this study was to evaluate the efficacy of a novel, knife-assisted snare resection (KAR) technique in the resection of scarred colonic polyps. This was a prospective cohort study of patients, in whom the KAR technique was used to resect scarred colonic polyps > 2  cm in size. Patients had previously undergone endoscopic mucosal resection (EMR) and developed recurrence, or EMR had been attempted but was aborted as a result of technical difficulty. A total of 42 patients underwent KAR of large (median 40  mm) scarred polyps. Surgery for benign disease was avoided in 38 of 41 patients (93 %). No life-threatening complications occurred. Recurrence was seen in six patients (16 %), five of whom underwent further endoscopic resection. The overall cure rate for KAR in complex scarred colonic polyps was 90 %. KAR of scarred colonic polyps by an expert endoscopist was an effective and safe technique with low recurrence rates. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Cooked navy and black bean diets improve biomarkers of colon health and reduce inflammation during colitis.

    Science.gov (United States)

    Zhang, Claire; Monk, Jennifer M; Lu, Jenifer T; Zarepoor, Leila; Wu, Wendy; Liu, Ronghua; Pauls, K Peter; Wood, Geoffrey A; Robinson, Lindsay; Tsao, Rong; Power, Krista A

    2014-05-01

    Common beans contain non-digestible fermentable components (SCFA precursors) and phenolic compounds (phenolic acids, flavonoids and anthocyanins) with demonstrated antioxidant and anti-inflammatory potential. The objective of the present study was to assess the in vivo effect of cooked whole-bean flours, with differing phenolic compound levels and profiles, in a mouse model of acute colitis. C57BL/6 mice were fed a 20 % navy bean or black bean flour-containing diet or an isoenergetic basal diet (BD) for 2 weeks before the induction of experimental colitis via 7 d dextran sodium sulphate (DSS, 2 % (w/v) in the drinking-water) exposure. Compared with the BD, both bean diets increased caecal SCFA and faecal phenolic compound concentrations (Pdiets reduced mRNA expression of colonic inflammatory cytokines (IL-6, IL-9, IFN-γ and IL-17A) and increased anti-inflammatory IL-10 (Pdiets enhanced DSS-induced colonic damage as indicated by an increased histological injury score and apoptosis (cleaved caspase-3 and FasL mRNA expression) (Pdiets exerted both beneficial and adverse effects during experimental colitis by reducing inflammatory biomarkers both locally and systemically while aggravating colonic mucosal damage. Further research is required to understand the mechanisms through which beans exert their effects on colonic inflammation and the impact on colitis severity in human subjects.

  1. Effects of silk sericin on the proliferation and apoptosis of colon cancer cells

    Directory of Open Access Journals (Sweden)

    Waraporn Kaewkorn

    2012-01-01

    Full Text Available Sericin is a silk protein woven from silkworm cocoons (Bombyx mori. In animal model, sericin has been reported to have anti-tumoral action against colon cancer. The mechanisms underlying the activity of sericin against cancer cells are not fully understood. The present study investigated the effects of sericin on human colorectal cancer SW480 cells compared to normal colonic mucosal FHC cells. Since the size of the sericin protein may be important for its activity, two ranges of molecular weight were tested. Sericin was found to decrease SW480 and FHC cell viability. The small sericin had higher anti-proliferative effects than that of the large sericin in both cell types. Increased apoptosis of SW480 cells is associated with increased caspase-3 activity and decreased Bcl-2 expression. The anti-proliferative effect of sericin was accompanied by cell cycle arrest at the S phase. Thus, sericin reduced SW480 cell viability by inducing cell apoptosis via caspase-3 activation and down-regulation of Bcl-2 expression. The present study provides scientific data that support the protective effect of silk sericin against cancer cells of the colon and suggests that this protein may have significant health benefits and could potentially be developed as a dietary supplement for colon cancer prevention.

  2. Mucosal delivery of liposome-chitosan nanoparticles complexes

    OpenAIRE

    Carvalho, Edison Samir Mascarelhas; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

    2009-01-01

    Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can...

  3. Mucosal defence along the gastrointestinal tract of cats and dogs

    OpenAIRE

    Stokes , Chris; Waly , Nashwa

    2006-01-01

    International audience; Diseases that are associated with infections or allergic reactions in the gastrointestinal and respiratory tracts are major causes of morbidity in both cats and dogs. Future strategies for the control of these conditions require a greater understanding of the cellular and molecular mechanisms involved in the induction and regulation of responses at the mucosal surfaces. Historically, the majority of the fundamental studies have been carried out in rodents or with tissu...

  4. Psittacid herpesviruses associated with mucosal papillomas in neotropical parrots

    International Nuclear Information System (INIS)

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

    2004-01-01

    Mucosal papillomas are relatively common lesions in several species of captive neotropical parrots. They cause considerable morbidity and in some cases, result in mortality. Previous efforts to identify papillomavirus DNA and proteins in these lesions have been largely unsuccessful. In contrast, increasing evidence suggests that mucosal papillomas may contain psittacid herpesviruses (PsHVs). In this study, 41 papillomas from 30 neotropical parrots were examined by PCR with PsHV-specific primers. All 41 papillomas were found to contain PsHV DNA. This 100% prevalence of PsHV infection in the papilloma population was found to be significantly higher than PsHV infection prevalence observed in other surveys of captive parrots. PsHV genotypes 1, 2, and 3, but not 4 were found in these lesions. Psittacus erithacus papillomavirus DNA and finch papillomavirus DNA were not found in the papillomas. A papilloma from a hyacinth macaw (Anodorhynchus hyacinthinus) was found to contain cells that had immunoreactivity to antiserum made to the common antigenic region of human papillomavirus (HPV) L1 major capsid protein. However, four other mucosal papillomas were negative for this immunoreactivity, and negative control tissues from a parrot embryo showed a similar staining pattern to that seen in the cloaca papilloma of the hyacinth macaw, strongly suggesting that the staining seen in hyacinth macaw papilloma was nonspecific. Based on these findings, it was concluded that specific genotypes of PsHV play a direct role in the development of mucosal papillomas of neotropical parrots and there is no evidence to suggest the concurrent presence of a papillomavirus in these lesions

  5. Enfermedad Diverticular del Colon

    Directory of Open Access Journals (Sweden)

    Gonzalo López Escobar

    1991-06-01

    Full Text Available

    Los divertículos del colon han sido reconocidos por varios observadores desde hace más de un siglo, pero en su mayor parte se trataba de casos aislados, hoy se la considera como la enfermedad del siglo XX, la de la era moderna y de los países industrializados y de avanzada tecnología (5,18,33.

    Según el diccionario de la Real Academia Española (11, divertículo, del latín, diverticulum, quiere decir desviación de un camino; y desde el punto de vista anatómico, apéndice hueco y terminado en fondo de saco. (Gráfica No. 1.

    Goligher (17 lo define como la “posada al borde del camino, probablemente un lugar, a menudo, de mala reputación”.

    Historia

    Según Hackford (18, el proceso fué descrito brevemente por Littre a comienzos del siglo XVIII; pero se le atribuye a Cruveilhier la primera descripción como proceso patológico en 1849, quien, además, mencionó: “encontramos, no rara vez, en el sigmoide, entre las bandas de fibras musculares longitudinales, una serie de pequeños tumores piriformes oscuros, que están formados por hernias de la mucosa a través de brechas en la capa muscular” (17.

    Fleischman en 1815 hizo la primera observación de la enfermedad y empleó el término divertículo (45.

    Rokitansky en 1.849, habló de una enfermedad adquirida y consideró que su causa consistía en la constipación (45.

    Virchowen 1853 describió la perisigmoiditis (45.

    En 1859 Sidney Jones informó de una fístula colo-vesical debida a diverticulitis (5,45.

    Loomis en 1870 describe una peritonitis como resultante de una diverticulitis (45.

    En 1877 Ball describió la anatomía patológica de la enfermedad y presentó dos casos de fístula colovesical debidas a diverticulitis (9. Cripps en 1.888 popularizó la colostomía de desviación como tratamiento para la fístula colovesical(18...

  6. Percutaneous drainage of colonic diverticular abscess: is colon resection necessary?

    Science.gov (United States)

    Gaertner, Wolfgang B; Willis, David J; Madoff, Robert D; Rothenberger, David A; Kwaan, Mary R; Belzer, George E; Melton, Genevieve B

    2013-05-01

    Recurrent diverticulitis has been reported in up to 30% to 40% of patients who recover from an episode of colonic diverticular abscess, so elective interval resection is traditionally recommended. The aim of this study was to review the outcomes of patients who underwent percutaneous drainage of colonic diverticular abscess without subsequent operative intervention. This was an observational study. This investigation was conducted at a tertiary care academic medical center and a single-hospital health system. Patients treated for symptomatic colonic diverticular abscess from 2002 through 2007 were included. The primary outcomes measured were complications, recurrence, and colectomy-free survival. Two hundred eighteen patients underwent percutaneous drainage of colonic diverticular abscesses. Thirty-two patients (15%) did not undergo subsequent colonic resection. Abscess location was pelvic (n = 9) and paracolic (n = 23), the mean abscess size was 4.2 cm, and the median duration of percutaneous drainage was 20 days. The comorbidities of this group of patients included severe cardiac disease (n = 16), immunodeficiency (n = 7), and severe pulmonary disease (n = 6). Freedom from recurrence at 7.4 years was 0.58 (95% CI 0.42-0.73). All recurrences were managed nonoperatively. Recurrence was significantly associated with an abscess size larger than 5 cm. Colectomy-free survival at 7.4 years was 0.17 (95% CI 0.13-0.21). This study was limited by its retrospective, nonexperimental design and short follow-up. In selected patients, observation after percutaneous drainage of colonic diverticular abscess appears to be a safe and low-risk management option.

  7. NHE8 plays important roles in gastric mucosal protection

    Science.gov (United States)

    Xu, Hua; Li, Jing; Chen, Huacong; Wang, Chunhui

    2013-01-01

    Sodium/hydrogen exchanger (NHE) 8 is an apically expressed membrane protein in the intestinal epithelial cells. It plays important roles in sodium absorption and bicarbonate secretion in the intestine. Although NHE8 mRNA has been detected in the stomach, the precise location and physiological role of NHE8 in the gastric glands remain unclear. In the current study, we successfully detected the expression of NHE8 in the glandular region of the stomach by Western blotting and located NHE8 protein at the apical membrane in the surface mucous cells by a confocal microscopic method. We also identified the expression of downregulated-in-adenoma (DRA) in the surface mucous cells in the stomach. Using NHE8−/− mice, we found that NHE8 plays little or no role in basal gastric acid production, yet NHE8−/− mice have reduced gastric mucosal surface pH and higher incidence of developing gastric ulcer. DRA expression was reduced significantly in the stomach in NHE8−/− mice. The propensity for gastric ulcer, reduced mucosal surface pH, and low DRA expression suggest that NHE8 is indirectly involved in gastric bicarbonate secretion and gastric mucosal protection. PMID:23220221

  8. Collagenous mucosal inflammatory diseases of the gastrointestinal tract.

    Science.gov (United States)

    Freeman, Hugh J

    2005-07-01

    Collagenous mucosal inflammatory diseases involve the columnar-lined gastric and intestinal mucosa and have become recognized increasingly as a significant cause of symptomatic morbidity, particularly in middle-aged and elderly women, especially with watery diarrhea. Still, mechanisms involved in the pathogenesis of this diarrhea remain poorly understood and require further elucidation. The prognosis and long-term outcome of these disorders has been documented only to a limited extent. Recent clinical and pathologic studies have indicated that collagenous mucosal inflammatory disease is a more extensive pathologic process that concomitantly may involve several sites in the gastric and intestinal mucosa. The dominant pathologic lesion is a distinct subepithelial hyaline-like deposit that has histochemical and ultrastructural features of collagen overlying a microscopically defined inflammatory process. An intimate relationship with other autoimmune connective tissue disorders is evident, particularly celiac disease. This is intriguing because these collagenous disorders have not been shown to be gluten dependent. Collagenous mucosal inflammatory disorders may represent a relatively unique but generalized inflammatory response to a multitude of causes, including celiac disease, along with a diverse group of pharmacologic agents. Some recent reports have documented treatment success but histopathologic reversal has been more difficult to substantiate owing to the focal, sometimes extensive nature, of this pathologic process.

  9. Cervical Intraepithelial Neoplasia Is Associated With Genital Tract Mucosal Inflammation

    Science.gov (United States)

    Mhatre, Mohak; McAndrew, Thomas; Carpenter, Colleen; Burk, Robert D.; Einstein, Mark H.; Herold, Betsy C.

    2013-01-01

    Background Clinical studies demonstrate increased prevalence of human papillomavirus (HPV)-associated disease in HIV-infected individuals and an increased risk of HIV acquisition in HPV-infected individuals. The mechanisms underlying this synergy are not defined. We hypothesize that women with cervical intraepithelial neoplasia (CIN) will exhibit changes in soluble mucosal immunity that may promote HPV persistence and facilitate HIV infection. Methods The concentrations of immune mediators and endogenous anti-Escherichia coli activity in genital tract secretions collected by cervicovaginal lavage were compared in HIV-negative women with high-risk HPV-positive (HRHPV+) CIN-3 (n = 37), HRHPV+ CIN-1 (n = 12), or PAP-negative control subjects (n = 57). Results Compared with control subjects, women with CIN-3 or CIN-1 displayed significantly higher levels of proinflammatory cytokines including interleukin (IL)-1α, IL-1β, and IL-8 (P < 0.002) and significantly lower levels of anti-inflammatory mediators and antimicrobial peptides, including IL-1 receptor antagonist, secretory leukocyte protease inhibitor (P < 0.01), and human β defensins 2 and 3 (P < 0.02). There was no significant difference in endogenous anti-E. coli activity after controlling for age and sample storage time. Conclusion HRHPV+ CIN is characterized by changes in soluble mucosal immunity that could contribute to HPV persistence. The observed mucosal inflammation suggests a mechanism that may also contribute to the epidemiologic link between persistent HPV and HIV. PMID:22801340

  10. Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts.

    Science.gov (United States)

    Waly, Mostafa I; Al-Rawahi, Amani S; Al Riyami, Marwa; Al-Kindi, Mohamed A; Al-Issaei, Halima K; Farooq, Sardar A; Al-Alawi, Ahmed; Rahman, Mohammad S

    2014-02-18

    Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Eighty Sprague-Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities.

  11. Aberrant expression of sonic hedgehog pathway in colon cancer and melanosis coli.

    Science.gov (United States)

    Wang, Zhong Chuan; Gao, Jun; Zi, Shu Ming; Yang, Ming; Du, Peng; Cui, Long

    2013-08-01

    To determine the hedgehog (Hh) signaling pathway correlated with the development of colon cancer and melanosis coli. Protein and mRNA levels of Hh signaling pathway components (sonic hedgehog [Shh], protein patched homolog 1 [Ptch 1], GLI family zinc finger 1 [Gli 1] and suppressor of fused homolog [Drosophila] [Sufu]) in 127 patients with colon cancer, 36 with melanosis coli and 20 adjacent normal mucosal tissues taken from surgical specimens were evaluated using antibody staining and quantitative real-time polymerase chain reaction. In adjacent normal tissue Shh and Ptch1, but not Gli1 or Sufu, were weakly expressed and mainly in the lining epithelium of the colonic mucosa. In cancerous tissues Shh and Gli1 were uniformly strong while Ptch1 was patchy and weak, and Sufu uniformly weak, which paralleled their levels of corresponding mRNA. Elevated protein levels of Shh and Ptch were significantly associated with mucinous colonic tissues. Elevated Sufu protein levels were positively correlated with the diameter and invasion of the tumor. In patients with melanosis coli, mRNA levels of Shh, Ptch1, Gli1 and Sufu were very low, which was similar to those of adjacent normal tissues; but protein levels of Shh, Ptch1 and Gli1, but not Sufu, were high, which was similar to those of cancerous tissues. The mRNA and protein levels of Hh pathway components are aberrantly elevated in colon cancer, which may be the potential molecular classification markers. Further studies are required to determine the role of melanosis coli in the colon tumorigenesis. © 2013 The Authors. Journal of Digestive Diseases © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

  12. Colonic wall changes in patients with diverticular disease - is there a predisposition for a complicated course?

    Science.gov (United States)

    Ulmer, T F; Rosch, R; Mossdorf, A; Alizai, H; Binnebösel, M; Neumann, U

    2014-01-01

    The aim of this study was to evaluate colonic wall changes and enteric neuropathy in patients with either uncomplicated (UDD) or complicated diverticular disease (CDD). Furthermore, we evaluated the presence of an anatomic sphincter at the rectosigmoid junction (RSJ). Samples of colonic tissue from fifteen patients with UDD, fifteen patients with CDD and fifteen patients as control were collected. Collagen quotient I/III was measured with the Sirius-red test, expression of MMP-1, MMP-13, innervation (S100), proliferation (Ki67) and apoptosis (TUNEL) in the colonic wall were investigated by immunohistochemical studies. Furthermore, measurements of the different layers were performed to investigate the RSJ. Patients with either UDD or CDD had lower collagen I/III quotients compared to the control group, significant for CDD (p = 0.007). For MMP-1 and MMP-13 only a slight increase for patients with CDD was found. The percentage of proliferating (Ki67) and apoptotic (TUNEL) cells was significantly higher for patients with CDD than in the control group (p = 0.016; p = 0.037). Upon investigating the S100-expression a significant reduce in glial cells density was found in the myenteric and mucosal plexus for both groups (UDD and CDD) compared to the control group. Measurements of the different colon layers oral, aboral and at the RSJ revealed equal values. This study has shown that colonic wall changes and enteric neuropathy seem to play a role in the pathogenesis of colonic diverticulosis. None of our results suggest a predisposition for a complicated diverticular disease. Furthermore, the presence of an anatomic sphincter at the rectosigmoid junction could not be detected. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  13. The Mucosal Adjuvant Cholera Toxin B Instructs Non-Mucosal Dendritic Cells to Promote IgA Production Via Retinoic Acid and TGF-β

    NARCIS (Netherlands)

    A.K. Gloudemans (Anouk); M. Plantinga (Maud); M. Guilliams (Martin); M.A. Willart (Monique); A. Ozir-Fazalalikhan (Arifa); A. van der Ham (Alwin); L. Boon (Louis); N.L. Harris (Nicola); H. Hammad (Hamida); H.C. Hoogsteden (Henk); M. Yazdanbakhsh (Maria); R.W. Hendriks (Rudi); B.N.M. Lambrecht (Bart); H.H. Smits (Hermelijn)

    2013-01-01

    textabstractIt is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing

  14. Cultivated vaginal microbiomes alter HIV-1 infection and antiretroviral efficacy in colonized epithelial multilayer cultures.

    Science.gov (United States)

    Pyles, Richard B; Vincent, Kathleen L; Baum, Marc M; Elsom, Barry; Miller, Aaron L; Maxwell, Carrie; Eaves-Pyles, Tonyia D; Li, Guangyu; Popov, Vsevolod L; Nusbaum, Rebecca J; Ferguson, Monique R

    2014-01-01

    There is a pressing need for modeling of the symbiotic and at times dysbiotic relationship established between bacterial microbiomes and human mucosal surfaces. In particular clinical studies have indicated that the complex vaginal microbiome (VMB) contributes to the protection against sexually-transmitted pathogens including the life-threatening human immunodeficiency virus (HIV-1). The human microbiome project has substantially increased our understanding of the complex bacterial communities in the vagina however, as is the case for most microbiomes, very few of the community member species have been successfully cultivated in the laboratory limiting the types of studies that can be completed. A genetically controlled ex vivo model system is critically needed to study the complex interactions and associated molecular dialog. We present the first vaginal mucosal culture model that supports colonization by both healthy and dysbiotic VMB from vaginal swabs collected from routine gynecological patients. The immortalized vaginal epithelial cells used in the model and VMB cryopreservation methods provide the opportunity to reproducibly create replicates for lab-based evaluations of this important mucosal/bacterial community interface. The culture system also contains HIV-1 susceptible cells allowing us to study the impact of representative microbiomes on replication. Our results show that our culture system supports stable and reproducible colonization by VMB representing distinct community state types and that the selected representatives have significantly different effects on the replication of HIV-1. Further, we show the utility of the system to predict unwanted alterations in efficacy or bacterial community profiles following topical application of a front line antiretroviral.

  15. Mucosal Healing and Risk of Lymphoproliferative Malignancy in Celiac Disease

    Science.gov (United States)

    Lebwohl, Benjamin; Granath, Fredrik; Ekbom, Anders; Smedby, Karin Ekström; Murray, Joseph A.; Neugut, Alfred I.; Green, Peter HR; Ludvigsson, Jonas F.

    2013-01-01

    Background Celiac disease (CD) is associated with an increased risk of lymphoproliferative malignancy (LPM). It is unknown whether this risk is affected by the results of the follow-up intestinal biopsy, performed to document mucosal healing. Objective To examine the association between mucosal healing in CD and later LPM. Design Population-based cohort study Setting We identified patients with CD from all of Sweden’s 28 pathology departments. Patients Individuals with CD who had a follow-up biopsy after initial diagnosis. Measurements We compared the risk of LPM to that of the general population using expected rates; and through Cox regression we compared the rate of LPM in those with persistent villous atrophy to those with mucosal healing. Results Among 7,625 patients with CD and a follow-up biopsy, persistent villous atrophy was present in 3,308 (43%). The overall risk of LPM was increased compared to the general population (Standardized incidence ratio, SIR 2.81; 95%CI 2.10–3.67), but this increase was greater among those with persistent villous atrophy (SIR 3.78; 95%CI 2.71–5.12) as compared to those with mucosal healing (SIR 1.50; 95%CI 0.77–2.62). Persistent villous atrophy compared to mucosal healing was associated with an increased risk of LPM (Hazard ratio, HR 2.26; 95%CI 1.18–4.34). We found an increased risk of T cell lymphoma (HR 3.51; 95%CI 0.75–16.34), but no excess risk of B cell lymphoma (HR 0.97; 95%CI 0.21–4.49). Limitation We had no data on dietary compliance. Conclusions The increased LPM risk in CD is associated with the results of the follow-up biopsy, with a higher risk among those with persistent villous atrophy. Follow-up biopsy may be a means to effectively stratify CD patients regarding subsequent LPM risk. Primary funding source the National Center for Advancing Translational Sciences, National Institutes of Health, The American Scandinavian Foundation, the Celiac Sprue Association, Örebro University Hospital, Karolinska

  16. Secreted protein acidic and rich in cysteine functions in colitis via IL17A regulation in mucosal CD4+ T cells.

    Science.gov (United States)

    Tanaka, Makoto; Takagi, Tomohisa; Naito, Yuji; Uchiyama, Kazuhiko; Hotta, Yuma; Toyokawa, Yuki; Ushiroda, Chihiro; Hirai, Yasuko; Aoi, Wataru; Higashimura, Yasuki; Mizushima, Katsura; Okayama, Tetsuya; Katada, Kazuhiro; Kamada, Kazuhiro; Ishikawa, Takeshi; Handa, Osamu; Itoh, Yoshito

    2018-03-01

    Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycol that regulates cell proliferation, tissue repair, and tumorigenesis. Despite evidence linking SPARC to inflammation, the mechanisms are unclear. Accordingly, the role of SPARC in intestinal inflammation was investigated. Colitis was induced in wild-type (WT) and SPARC knockout (KO) mice using trinitrobenzene sulfonic acid (TNBS). Colons were assessed for damage; leukocyte infiltration; Tnf, Ifng, Il17a, and Il10 mRNA expression; and histology. Cytokine profiling of colonic lamina propria mononuclear cells (LPMCs) was performed by flow cytometry. Naïve CD4 + T cells were isolated from WT and SPARC KO mouse spleens, and the effect of SPARC on Th17 cell differentiation was examined. Recombination activating gene 1 knockout (RAG1 KO) mice reconstituted with T cells from either WT or SPARC KO mice were investigated. Trinitrobenzene sulfonic acid exposure significantly reduced bodyweight and increased mucosal inflammation, leukocyte infiltration, and Il17a mRNA expression in WT relative to SPARC KO mice. The percentage of IL17A-producing CD4 + T cells among LPMCs from KO mice was lower than that in WT mice when both groups were exposed to TNBS. Th17 cell differentiation was suppressed in cells from SPARC KO mice. In the T cell transfer colitis model, RAG1 KO mice receiving T cells from WT mice were more severely affected than those reconstituted with cells from SPARC KO mice. Secreted protein acidic and rich in cysteine accelerates colonic mucosal inflammation via modulation of IL17A-producing CD4 + T cells. SPARC is a potential therapeutic target for conditions involving intestinal inflammation. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  17. Slc5a8, a Na+-coupled high-affinity transporter for short-chain fatty acids, is a conditional tumour suppressor in colon that protects against colitis and colon cancer under low-fibre dietary conditions.

    Science.gov (United States)

    Gurav, Ashish; Sivaprakasam, Sathish; Bhutia, Yangzom D; Boettger, Thomas; Singh, Nagendra; Ganapathy, Vadivel

    2015-07-15

    Mammalian colon harbours trillions of bacteria under physiological conditions; this symbiosis is made possible because of a tolerized response from the mucosal immune system. The mechanisms underlying this tolerogenic phenomenon remain poorly understood. In the present study we show that Slc5a8 (solute carrier gene family 5a, member 8), a Na(+)-coupled high-affinity transporter in colon for the bacterial fermentation product butyrate, plays a critical role in this process. Among various immune cells in colon, dendritic cells (DCs) are unique not only in their accessibility to luminal contents but also in their ability to induce tolerogenic phenotype in T-cells. We found that DCs exposed to butyrate express the immunosuppressive enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and aldehyde dehydrogenase 1A2 (Aldh1A2), promote conversion of naive T-cells into immunosuppressive forkhead box P3(+) (FoxP3(+)) Tregs (regulatory T-cells) and suppress conversion of naive T-cells into pro-inflammatory interferon (IFN)-γ-producing cells. Slc5a8-null DCs do not induce IDO1 and Aldh1A2 and do not generate Tregs or suppress IFN-γ-producing T-cells in response to butyrate. We also provide in vivo evidence for an obligatory role for Slc5a8 in suppression of IFN-γ-producing T-cells. Furthermore, Slc5a8 protects against colitis and colon cancer under conditions of low-fibre intake but not when dietary fibre intake is optimal. This agrees with the high-affinity nature of the transporter to mediate butyrate entry into cells. We conclude that Slc5a8 is an obligatory link between dietary fibre and mucosal immune system via the bacterial metabolite butyrate and that this transporter is a conditional tumour suppressor in colon linked to dietary fibre content. © 2015 Authors; published by Portland Press Limited.

  18. The Economics of Colon Cancer.

    Science.gov (United States)

    Orangio, Guy R

    2018-04-01

    The economic burden of cancer on the national health expenditure is billions of dollars. The economic cost is measured on direct and indirect medical costs, which vary depending on stage at diagnosis, patient age, type of medical services, and site of service. Costs vary by region, physician behavior, and patient preferences. When analyzing the economic burden of survivors of colon cancer, we cannot forget the societal burden. Post-acute care and readmissions are major economic burdens. People with colon cancer have to be followed for their lifetime. Economic models are being studied to give cost-effective solutions to this problem. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Neurological manifestation of colonic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Uzair Chaudhary

    2012-04-01

    Full Text Available Paraneoplastic neurologic disorders are extremely rare in cancer patients and are most commonly associated with certain tumors, such as ovarian cancer, small cell lung cancer, and breast cancer. We report here a paraneoplastic neurological syndrome in a 53-year-old man with colonic adenocarcinoma with a solitary liver metastasis. His paraneoplastic syndrome was successfully treated by methylprednisolone and primary oncologic therapies including neoadjuvant chemotherapy and definitive surgery. This is also the first documented case of simultaneous manifestation of a sensory neuropathy and limbic encephalitis with colon cancer.

  20. Combination of gefitinib and DNA methylation inhibitor decitabine exerts synergistic anti-cancer activity in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Yun-feng Lou

    Full Text Available Despite recent advances in the treatment of human colon cancer, the chemotherapy efficacy against colon cancer is still unsatisfactory. In the present study, effects of concomitant inhibition of the epidermal growth factor receptor (EGFR and DNA methyltransferase were examined in human colon cancer cells. We demonstrated that decitabine (a DNA methyltransferase inhibitor synergized with gefitinib (an EGFR inhibitor to reduce cell viability and colony formation in SW1116 and LOVO cells. However, the combination of the two compounds displayed minimal toxicity to NCM460 cells, a normal human colon mucosal epithelial cell line. The combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. In addition, the combination of decitabine with gefitinib markedly inhibited colon cancer cell migration. Furthermore, gefitinib synergistically enhanced decitabine-induced cytotoxicity was primarily due to apoptosis as shown by Annexin V labeling that was attenuated by z-VAD-fmk, a pan caspase inhibitor. Concomitantly, cell apoptosis resulting from the co-treatment of gefitinib and decitabine was accompanied by induction of BAX, cleaved caspase 3 and cleaved PARP, along with reduction of Bcl-2 compared to treatment with either drug alone. Interestingly, combined treatment with these two drugs increased the expression of XIAP-associated factor 1 (XAF1 which play an important role in cell apoptosis. Moreover, small interfering RNA (siRNA depletion of XAF1 significantly attenuated colon cancer cells apoptosis induced by the combination of the two drugs. Our findings suggested that gefitinib in combination with decitabine exerted enhanced cell apoptosis in colon cancer cells were involved in mitochondrial-mediated pathway and induction of XAF1 expression. In conclusion, based on the observations from our study, we suggested that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating colon

  1. Lack of association of colonic epithelium telomere length and oxidative DNA damage in Type 2 diabetes under good metabolic control

    Directory of Open Access Journals (Sweden)

    Kennedy Hugh

    2008-10-01

    Full Text Available Abstract Background Telomeres are DNA repeat sequences necessary for DNA replication which shorten at cell division at a rate directly related to levels of oxidative stress. Critical telomere shortening predisposes to cell senescence and to epithelial malignancies. Type 2 diabetes is characterised by increased oxidative DNA damage, telomere attrition, and an increased risk of colonic malignancy. We hypothesised that the colonic mucosa in Type 2 diabetes would be characterised by increased DNA damage and telomere shortening. Methods We examined telomere length (by flow fluorescent in situ hybridization and oxidative DNA damage (flow cytometry of 8 – oxoguanosine in the colonic mucosal cells of subjects with type 2 diabetes (n = 10; mean age 62.2 years, mean HbA1c 6.9% and 22 matched control subjects. No colonic pathology was apparent in these subjects at routine gastrointestinal investigations. Results Mean colonic epithelial telomere length in the diabetes group was not significantly different from controls (10.6 [3.6] vs. 12.1 [3.4] Molecular Equivalent of Soluble Fluorochrome Units [MESF]; P = 0.5. Levels of oxidative DNA damage were similar in both T2DM and control groups (2.6 [0.6] vs. 2.5 [0.6] Mean Fluorescent Intensity [MFI]; P = 0.7. There was no significant relationship between oxidative DNA damage and telomere length in either group (both p > 0.1. Conclusion Colonic epithelium in Type 2 diabetes does not differ significantly from control colonic epithelium in oxidative DNA damage or telomere length. There is no evidence in this study for increased oxidative DNA damage or significant telomere attrition in colonic mucosa as a carcinogenic mechanism.

  2. Beer as colon lavage preparation

    International Nuclear Information System (INIS)

    Kinnunen, J.; Linden, H.; Pietilae, J.; Juutilainen, T.

    1987-01-01

    Six patients received beer preparation prior to double contrast barium enema. The beer group scored slightly better (though not statistically significantly) both in the cleanliness and in the mucosal coating of the bowel than the control group with standard preparation. The fluid balance was unaltered. The patients in the beer group felt surprisingly well, likely due to the good fluid and energy balance provided by the beer. The beer preparation could be used in cases, when the patients are ready to intake beer and want to maintain a good nutritional status. (orig.) [de

  3. Impaired barrier function by dietary fructo-oligosaccharides (FOS in rats is accompanied by increased colonic mitochondrial gene expression

    Directory of Open Access Journals (Sweden)

    Kramer Evelien

    2008-03-01

    Full Text Available Abstract Background Dietary non-digestible carbohydrates stimulate the gut microflora and are therefore presumed to improve host resistance to intestinal infections. However, several strictly controlled rat infection studies showed that non-digestible fructo-oligosaccharides (FOS increase, rather than decrease, translocation of Salmonella towards extra-intestinal sites. In addition, it was shown that FOS increases intestinal permeability already before infection. The mechanism responsible for this adverse effect of FOS is unclear. Possible explanations are altered mucosal integrity due to changes in tight junctions or changes in expression of defense molecules such as antimicrobials and mucins. To examine the mechanisms underlying weakening of the intestinal barrier by FOS, a controlled dietary intervention study was performed. Two groups of 12 rats were adapted to a diet with or without FOS. mRNA was collected from colonic mucosa and changes in gene expression were assessed for each individual rat using Agilent rat whole genome microarrays. Results Among the 997 FOS induced genes we observed less mucosal integrity related genes than expected with the clear permeability changes. FOS did not induce changes in tight junction genes and only 8 genes related to mucosal defense were induced by FOS. These small effects are unlikely the cause for the clear increase in intestinal permeability that is observed. FOS significantly increased expression of 177 mitochondria-related genes. More specifically, induced expression of genes involved in all five OXPHOS complexes and the TCA cycle was observed. These results indicate that dietary FOS influences intestinal mucosal energy metabolism. Furthermore, increased expression of 113 genes related to protein turnover, including proteasome genes, ribosomal genes and protein maturation related genes, was seen. FOS upregulated expression of the peptide hormone proglucagon gene, in agreement with previous studies, as

  4. MALToma of the Transverse colon, Ascending colon and Caecum: A ...

    African Journals Online (AJOL)

    Background The stomach is the most common site formucosa - associated lymphoid tissue [MALT] lymphoma (MALToma). MALToma of the colon is a rare occurrence. It is on this background that we report this case. Methods The case records a patient with a MALT lymphoma and a review of the literature on the subject ...

  5. Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract.

    Science.gov (United States)

    Kon, Risako; Ikarashi, Nobutomo; Nagoya, Chika; Takayama, Tomoko; Kusunoki, Yoshiki; Ishii, Makoto; Ueda, Harumi; Ochiai, Wataru; Machida, Yoshiaki; Sugita, Kazuyuki; Sugiyama, Kiyoshi

    2014-02-27

    Aquaporin-3 (AQP3) is expressed in mucosal epithelial cells in the colon and is important for regulating fecal water content. We examined the role of AQP3 in the laxative effect of rhubarb extract. After orally administering rhubarb extract or its major component (sennoside A) to rats, the fecal water content, AQP3 expression and prostaglandin E2 (PGE2) concentrations in the colon were examined. The mechanism by which sennoside A decreases the expression of AQP3 was examined using the human colon cancer HT-29 cells and macrophage-derived Raw264.7 cells. During diarrhea by rhubarb extract administration, the PGE2 levels in the colon increased while the AQP3 expression significantly decreased. Similar changes were also observed when sennoside A was administered. When sennoside A or its metabolites, rheinanthrone and rhein were added to Raw264.7 cells, a significant increase in the PGE2 concentration was observed only in cells treated with rheinanthrone. Fifteen minutes after adding PGE2 to the HT-29 cells, the AQP3 expression decreased to approximately 40% of the control. When pretreated with indomethacin, sennoside A neither decreased the AQP3 expression nor induced diarrhea. Sennoside A may decrease AQP3 expression in the colon to inhibit water transport from the luminal to the vascular side, leading to a laxative effect. The decreases in the levels of AQP3 are caused by rheinanthrone, which is a metabolite of sennoside A, this metabolite activates the macrophages in the colon and increases the secretion of PGE2; PGE2 acts as a paracrine factor and decreases AQP3 expression in colon mucosal epithelial cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Dietary flaxseed modulates the colonic microenvironment in healthy C57Bl/6 male mice which may alter susceptibility to gut-associated diseases.

    Science.gov (United States)

    Power, Krista A; Lepp, Dion; Zarepoor, Leila; Monk, Jennifer M; Wu, Wenqing; Tsao, Rong; Liu, Ronghua

    2016-02-01

    Understanding how dietary components alter the healthy baseline colonic microenvironment is important in determining their roles in influencing gut health and gut-associated diseases. Dietary flaxseed (FS) has demonstrated anti-colon cancer effects in numerous rodent models, however, exacerbated acute colonic mucosal injury and inflammation in a colitis model. This study investigates whether FS alters critical aspects of gut health in healthy unchallenged mice, which may help explain some of the divergent effects observed following different gut-associated disease challenges. Four-week-old C57Bl/6 male mice were fed an AIN-93G basal diet (BD) or an isocaloric BD+10% ground FS diet for 3 weeks. FS enhanced colon goblet cell density, mucus production, MUC2 mRNA expression, and cecal short chain fatty acid levels, indicative of beneficial intestinal barrier integrity responses. Additionally, FS enhanced colonic regenerating islet-derived protein 3 gamma (RegIIIγ) and reduced MUC1 and resistin-like molecule beta (RELMβ) mRNA expression which may indicate altered responses in regulating microbial defense and injury repair responses. FS diet altered the fecal microbial community structure (16S rRNA gene profiling), including a 20-fold increase in Prevotella spp. and a 30-fold reduction in Akkermansia muciniphila abundance. A 10-fold reduction in A. muciniphila abundance by FS was also demonstrated in the colon tissue-associated microbiota (quantitative PCR). Furthermore, fecal branched chain fatty acids were increased by FS, indicative of increased microbial-derived putrefactive compounds. In conclusion, consumption of a FS-supplemented diet alters the baseline colonic microenvironment of healthy mice which may modify subsequent mucosal microbial defense and injury-repair responses leading to altered susceptibility to different gut-associated diseases. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  7. Laparoscopic mobilization for resection of the transverse colon for cancer: a simple, reproducible method.

    Science.gov (United States)

    Komolafe, Olusegun O; Melani, Armando G; Véo, Carlos A; Denadai, Marcos V; de Oliveira, Júnea C

    2012-10-01

    Laparoscopic resection for colorectal cancer by appropriately skilled surgeons is now accepted as safe and oncologically sound. Much of the contemporary debate in this area is regarding appropriate training of surgeons, as there is a steep learning curve. Arguably, the most difficult aspect of laparoscopic colon resection is mobilization of the transverse colon, with division of the middle colic artery. Mobilizing the transverse colon is necessary for many colonic resections, including "introductory" procedures. Our department has a consistent, sequential method for mobilization of the transverse colon with proximal isolation and ligation of the middle colic artery as indicated. This involves using the head, or distal body, of the pancreas as a landmark, for right-sided and left-sided resections, respectively. We believe that this particular methodology is easy to learn and surgically efficient. We also discuss some particular intraoperative problems and scenarios, with suggested solutions.

  8. Evolving colon injury management: a review.

    Science.gov (United States)

    Greer, Lauren T; Gillern, Suzanne M; Vertrees, Amy E

    2013-02-01

    The colon is the second most commonly injured intra-abdominal organ in penetrating trauma. Management of traumatic colon injuries has evolved significantly over the past 200 years. Traumatic colon injuries can have a wide spectrum of severity, presentation, and management options. There is strong evidence that most non-destructive colon injuries can be successfully managed with primary repair or primary anastomosis. The management of destructive colon injuries remains controversial with most favoring resection with primary anastomosis and others favor colonic diversion in specific circumstances. The historical management of traumatic colon injuries, common mechanisms of injury, demographics, presentation, assessment, diagnosis, management, and complications of traumatic colon injuries both in civilian and military practice are reviewed. The damage control revolution has added another layer of complexity to management with continued controversy.

  9. Colon Trauma: Evidence-Based Practices.

    Science.gov (United States)

    Yamamoto, Ryo; Logue, Alicia J; Muir, Mark T

    2018-01-01

    Colon injury is not uncommon and occurs in about a half of patients with penetrating hollow viscus injuries. Despite major advances in the operative management of penetrating colon wounds, there remains discussion regarding the appropriate treatment of destructive colon injuries, with a significant amount of scientific evidence supporting segmental resection with primary anastomosis in most patients without comorbidities or large transfusion requirement. Although literature is sparse concerning the management of blunt colon injuries, some studies have shown operative decision based on an algorithm originally defined for penetrating wounds should be considered in blunt colon injuries. The optimal management of colonic injuries in patients requiring damage control surgery (DCS) also remains controversial. Studies have recently reported that there is no increased risk compared with patients treated without DCS if fascial closure is completed on the first reoperation, or that a management algorithm for penetrating colon wounds is probably efficacious for colon injuries in the setting of DCS as well.

  10. Conservative management of colonic injury during percutaneous ...

    African Journals Online (AJOL)

    M. Elghoneimy

    2016-02-22

    Feb 22, 2016 ... Patients' records were searched for the occurrence of colonic injury. Records were ... tion to opacify the system and the percutaneous renal access was .... identify the presence of a retrorenal colon, yet the rarity of such a.

  11. Prehistoric human colonization of India

    Indian Academy of Sciences (India)

    Unknown

    J. Biosci. | Vol. 26 | No. 4 | Suppl. | November 2001. V N Misra. 492 ... humans differ from the other apes in their upright posture, ... characterized by Levallois flakes and blades and by the ... and the coastal region running parallel to them, northeast ..... November 2001. Prehistoric human colonization of India. 497. Figure 1.

  12. Trophic factors in the treatment and prevention of alimentary tract mucositis

    DEFF Research Database (Denmark)

    Rathe, Mathias; Shen, Rene L; Sangild, Per T

    2018-01-01

    PURPOSE OF REVIEW: Mucositis is a common adverse effect of cytotoxic anticancer treatment with serious implications for the quality of life, morbidity and mortality of cancers patients. Although, evidence supporting the use of certain treatments exists there is no gold standard for preventing...... clinical trials and uniform reporting of mucositis, are important elements to help establish new standard interventions that can be included into the continuously updated clinical recommendations for treatment of mucositis....

  13. Acute pseudo-obstruction of the colon

    International Nuclear Information System (INIS)

    Beese, M.; Heller, M.

    1988-01-01

    The radiological correlate to the pseudo-obstruction of the colon is not specific, but it does supply a pointer to the disease of it shows dilation of the caecum, colon ascendens and colon transversum with air-pockets and reflected imaging as well as a usually not dilated colon descendens with remarkably little air. To make the diagnosis quite sure we must exclude intestinal obstruction by using X-ray contrast media or by coloscopy. (orig./GDG) [de

  14. Laparoscopic colectomy for transverse colon carcinoma.

    Science.gov (United States)

    Zmora, O; Bar-Dayan, A; Khaikin, M; Lebeydev, A; Shabtai, M; Ayalon, A; Rosin, D

    2010-03-01

    Laparoscopic resection of transverse colon carcinoma is technically demanding and was excluded from most of the large trials of laparoscopic colectomy. The aim of this study was to assess the safety, feasibility, and outcome of laparoscopic resection of carcinoma of the transverse colon. A retrospective review was performed to identify patients who underwent laparoscopic resection of transverse colon carcinoma. These patients were compared to patients who had laparoscopic resection for right and sigmoid colon carcinoma. In addition, they were compared to a historical series of patients who underwent open resection for transverse colon cancer. A total of 22 patients underwent laparoscopic resection for transverse colon carcinoma. Sixty-eight patients operated for right colon cancer and 64 operated for sigmoid colon cancer served as comparison groups. Twenty-four patients were identified for the historical open group. Intraoperative complications occurred in 4.5% of patients with transverse colon cancer compared to 5.9% (P = 1.0) and 7.8% (P = 1.0) of patients with right and sigmoid colon cancer, respectively. The early postoperative complication rate was 45, 50 (P = 1.0), and 37.5% (P = 0.22) in the three groups, respectively. Conversion was required in 1 (5%) patient in the laparoscopic transverse colon group. The conversion rate and late complications were not significantly different in the three groups. There was no significant difference in the number of lymph nodes harvested in the laparoscopic and open groups. Operative time was significantly longer in the laparoscopic transverse colectomy group when compared to all other groups (P = 0.001, 0.008, and transverse colectomy, respectively). The results of laparoscopic colon resection for transverse colon carcinoma are comparable to the results of laparoscopic resection of right or sigmoid colon cancer and open resection of transverse colon carcinoma. These results suggest that laparoscopic resection of transverse

  15. Protective effects of Astragalus-Lilygranules on intestinal mucosal barrier of mice in high altitude hypoxia

    Directory of Open Access Journals (Sweden)

    Ling LI

    2016-10-01

    .05. The pathological score of intestinal mucosal necrosis and edema in small intestine (2.30±1.33, 2.10±0.94 respectively and colon (2.50±1.08, 1.90±0.99 were lower than those of model group and inflammatory cell count (small intestine 13.26±2.34, 10.93±3.67/HP, colon 14.40±2.02, 11.33±2.96/HP, respectively were lower than those of the model group (P<0.05, and the HIF-1αexpression in the intestinal tissues increased significantly compared with the model group (P<0.01. Conclusion  ALP has certain protective effect on intestinal mucosa and microecology of mice under high altitude hypoxia condition. DOI: 10.11855/j.issn.0577-7402.2016.09.15

  16. Type 1 diabetes in children is not a predisposing factor for oral yeast colonization.

    Science.gov (United States)

    Costa, Ana L; Silva, Branca M A; Soares, Rui; Mota, Diana; Alves, Vera; Mirante, Alice; Ramos, João C; Maló de Abreu, João; Santos-Rosa, Manuel; Caramelo, Francisco; Gonçalves, Teresa

    2017-06-01

    Type 1 diabetes mellitus (T1D) is considered a risk factor associated with oral yeast infections. The aim of this study was to evaluate the yeast oral carriage (in saliva and mucosal surface) of children with T1D and potential relation with host factors, particularly the subset of CD4+ T cells. Yeasts were quantified and identified in stimulated saliva and in cheek mucosal swabs of 133 diabetic T1D and 72 healthy control subjects. Salivary lymphocytes were quantified using flow cytometry. The presence of yeasts in the oral cavity (60% of total patients) was not affected by diabetes, metabolic control, duration of the disease, salivary flow rate or saliva buffer capacity, by age, sex, place of residence, number of daily meals, consumption of sweets or frequency of tooth brushing. Candida albicans was the most prevalent yeast species, but a higher number of yeast species was isolated in nondiabetics. T1D children with HbA1c ≤ 7.5 (metabolically controlled) presented higher number of CD4+ T salivary subsets when compared with the other groups of children (non-diabetic and nonmetabolically controlled) and also presented the highest number of individuals without oral yeast colonization. In conclusion, T1D does not predisposes for increased oral yeast colonization and a higher number of salivary CD4+T cells seems to result in the absence of oral colonization by yeasts. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Interactions between bacteria and the gut mucosa: Do enteric neurotransmitters acting on the mucosal epithelium influence intestinal colonization or infection?

    Science.gov (United States)

    The intestinal epithelium is a critical barrier between the internal and external milieux of the mammalian host. Epithelial interactions between these two host environments have been shown to be modulated by several different, cross-communicating cell types residing in the gut mucosa. These include ...

  18. Proteome stability analysis of snap frozen, RNAlater preserved, and formalin-fixed paraffin-embedded human colon mucosal biopsies

    DEFF Research Database (Denmark)

    Bjerg Bennike, Tue; Kastaniegaard, Kenneth; Padurariu, Simona

    2016-01-01

    Large repositories of well characterized RNAlater preserved samples and formalin-fixed, paraffin-embedded samples have been generated worldwide. However, the impact on the proteome of the preservation methods remain poorly described. Therefore, we analyzed the impact on the proteome of preserving...... samples in RNAlater, and by formalin-fixation, paraffin-embedding on human soft tissue, using directly frozen samples as a control ("Comparing the proteome of snap frozen, RNAlater preserved, and formalin-fixed paraffin-embedded human tissue samples" [1]). We here report the data from the analysis...

  19. Proteome stability analysis of snap frozen, RNAlater preserved, and formalin-fixed paraffin-embedded human colon mucosal biopsies

    DEFF Research Database (Denmark)

    Bennike, Tue Bjerg; Kastaniegaard, Kenneth; Padurariu, Simona

    2016-01-01

    Large repositories of well characterized RNAlater preserved samples and formalin-fixed, paraffin-embedded samples have been generated worldwide. However, the impact on the proteome of the preservation methods remain poorly described. Therefore, we analyzed the impact on the proteome of preserving...... throughput gel free quantitative proteomics. The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PRIDE: PXD002029....

  20. Increased melatonin in oral mucosal tissue of oral lichen planus (OLP) patients: A possible link between melatonin and its role in oral mucosal inflammation.

    Science.gov (United States)

    Luengtrakoon, Kirawut; Wannakasemsuk, Worraned; Vichitrananda, Vilasinee; Klanrit, Poramaporn; Hormdee, Doosadee; Noisombut, Rajda; Chaiyarit, Ponlatham

    2017-06-01

    The existence of extra-pineal melatonin has been observed in various tissues. No prior studies of melatonin in human oral mucosal tissue under the condition of chronic inflammation have been reported. The aim of this study was to investigate the presence of melatonin in oral mucosal tissue of patients with oral lichen planus (OLP) which was considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations. Sections from formalin-fixed and paraffin-embedded oral mucosal tissue of OLP patients (n=30), and control subjects (n=30) were used in this study. Immunohistochemical staining was performed and the semiquantitative scoring system was used to assess the levels of arylalkylamine-N-acetyltransferase (AANAT: a rate-limiting enzyme in the biosynthesis pathway of melatonin), melatonin, and melatonin receptor 1 (MT1) in oral mucosa of OLP patients and normal oral mucosa of control subjects. AANAT, melatonin, and MT1were detected in oral mucosal tissue of OLP patients and control subjects. Immunostaining scores of AANAT, melatonin, and MT1 in oral mucosal tissue of OLP patients were significantly higher than those in control subjects (p=0.002, poral mucosal tissue of OLP patients imply that chronic inflammation may induce the local biosynthesis of melatonin via AANAT, and may enhance the action of melatonin via MT1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. CALCIUM AND THE PREVENTION OF COLON CANCER

    NARCIS (Netherlands)

    WELBERG, JWM; KLEIBEUKER, JH; VANDERMEER, R; MULDER, NH; DEVRIES, EGE

    1991-01-01

    Diet is a major determinant of colon cancer risk. Calcium may protect against colon cancer, presumably by binding cytotoxic bile acids and fatty acids. Numerous studies support this proposition. In subjects at risk for colon cancer oral calcium supplementation has been shown to reduce rectal

  2. Congenital Diverticular Disease of the Entire Colon

    Directory of Open Access Journals (Sweden)

    A. Patel

    2013-01-01

    Full Text Available Congenital or true colonic diverticulosis is a rare condition typified by the preservation of the colonic wall architecture within the diverticular outpouching. Cases of multiple jejunal diverticula have been reported as well as cases of solitary giant diverticula of the colon. There have been no reports in the literature of pancolonic congenital diverticulosis.

  3. Human colorectal mucosal microbiota correlates with its host niche physiology revealed by endomicroscopy.

    Science.gov (United States)

    Wang, Ai-Hua; Li, Ming; Li, Chang-Qing; Kou, Guan-Jun; Zuo, Xiu-Li; Li, Yan-Qing

    2016-02-26

    The human gut microbiota plays a pivotal role in the maintenance of health, but how the microbiota interacts with the host at the colorectal mucosa is poorly understood. We proposed that confocal laser endomicroscopy (CLE) might help to untangle this relationship by providing in vivo physiological information of the mucosa. We used CLE to evaluate the in vivo physiology of human colorectal mucosa, and the mucosal microbiota was quantified using 16 s rDNA pyrosequencing. The human mucosal microbiota agglomerated to three major clusters dominated by Prevotella, Bacteroides and Lactococcus. The mucosal microbiota clusters did not significantly correlate with the disease status or biopsy sites but closely correlated with the mucosal niche physiology, which was non-invasively revealed by CLE. Inflammation tilted two subnetworks within the mucosal microbiota. Infiltration of inflammatory cells significantly correlated with multiple components in the predicted metagenome, such as the VirD2 component of the type IV secretory pathway. Our data suggest that a close correlation exists between the mucosal microbiota and the colorectal mucosal physiology, and CLE is a clinically available tool that can be used to facilitate the study of the in vivo correlation between colorectal mucosal physiology and the mucosal microbiota.

  4. Pretreatment with Saccharomyces boulardii does not prevent the experimental mucositis in Swiss mice.

    Science.gov (United States)

    Maioli, Tatiani Uceli; de Melo Silva, Brenda; Dias, Michelle Nobre; Paiva, Nivea Carolina; Cardoso, Valbert Nascimento; Fernandes, Simone Odilia; Carneiro, Cláudia Martins; Dos Santos Martins, Flaviano; de Vasconcelos Generoso, Simone

    2014-04-11

    The antimetabolite chemotherapy 5-Fluorouracil is one of the most commonly prescribed drugs in clinical cancer treatment. Although this drug is not specific for cancer cells and also acts on healthy cells, it can cause mucositis, a common collateral effect. Dysbiosis has also been described in 5-fluorouracil-induced mucositis and is likely to contribute to the overall development of mucositis. In light of this theory, the use of probiotics could be a helpful strategy to alleviate mucositis. So the aim of this study was evaluate the impact of the probiotic Saccharomyces boulardii in a model of mucositis. After induced of mucositis, mice from the Mucositis groups showed a decrease in food consumption (p Saccharomyces boulardii did not reverse this effect (p > 0.05). Mucositis induced an increase in intestinal permeability and intestinal inflammation (p  0.05) in mice pretreated with S. boulardii. S. boulardii was not able to prevent the effects of experimental mucositis induced by 5- Fluorouracil.

  5. Oral cryotherapy reduces mucositis and opioid use after myeloablative therapy--a randomized controlled trial.

    Science.gov (United States)

    Svanberg, Anncarin; Birgegård, Gunnar; Ohrn, Kerstin

    2007-10-01

    Mucositis is a major complication in myeloablative therapy, which often necessitates advanced pharmacological pain treatment, including i.v. opioids. Attempts to prevent oral mucositis have included oral cryotherapy, which has been shown to reduce mucositis, but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation (BMT). The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v. opioids among patients who receive myeloablative therapy before BMT. Eighty patients 18 years and older, scheduled for BMT, were included consecutively and randomised to oral cryotherapy or standard oral care. A stratified randomisation was used with regard to type of transplantation. Intensity of pain, severity of mucositis and use of opioids were recorded using pain visual analogue scale (VAS) scores, mucositis index scores and medical and nursing charts. This study showed that patients receiving oral cryotherapy had less pronounced mucositis and significantly fewer days with i.v. opioids than the control group. In the autologous setting, cryotherapy patients also needed significantly lower total dose of opioids. Oral cryotherapy is an effective and well-tolerated therapy to alleviate mucositis and consequently reduce the number of days with i.v. opioids among patients treated with myeloablative therapy before BMT.

  6. Prevalence of oral mucosal lesions among chewing tobacco users: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Sujatha S Reddy

    2015-01-01

    Statistical Analysis Used: Chi-square and Fisher′s exact tests were used to assess the statistical significance. Results: Of the 901 subjects with CT habits, 55.8% revealed no clinically detectable oral mucosal changes and 44.1% showed mucosal changes of which 63.8% were males and 36.1% were females. The most common finding was chewers mucositis (59.5% followed by submucous fibrosis (22.8%, leukoplakia (8%, lichenoid reaction (6.5%, oral cancer (2.7%, and lichen planus (0.5%. Conclusion: This study provides information about different CT habits and associated mucosal lesions among this population.

  7. Histopathological analysis of gastric mucosal biopsies in non ulcer dyspepsia

    International Nuclear Information System (INIS)

    Sarfraz, T.; Hafeez, M.; Tariq, H.; Azhar, M.

    2016-01-01

    Objective: To find out the pattern of gastric mucosal histopathological findings in gastric biopsies of patients with non ulcer dyspepsia. Study Design: Prospective descriptive study. Place and Duration of Study: Histopathology department Combined Military Hospital (CMH) Kharian Pakistan from Jan to Dec 2015. Material and Methods: One hundred patients presenting at outpatient gastroenterology department with dyspepsia having no endoscopic lesion were included in the study. Two gastric mucosal biopsies from antrum and two from corpus were taken. The specimens were processed and examined histologically to see the changes. Results: Gastric biopsies of 100 patients including 65 males and 35 females presenting with non ulcer dyspepsia were studied. Most of the patients were between the age group of 31-50 years. Histological examination of gastric biopsies revealed 70 percent of patients having histological features of gastritis, while 30 percent having no significant histological finding. Chronic inflammation was seen in 70 cases (70 percent), activity in 15 cases (15 percent), glandular atrophy in 2 cases (2 percent) and intestinal metaplasia in 2 cases (2 percent). H.Pylori were identified in 25 cases (25 percent) based on haematoxylin and eosin (H and E) staining and modified giemsa staining. Conclusion: Most the cases of non ulcer dyspepsia show histological evidence of gastritis, however a significant number of patients showed no gastric mucosal histological abnormality. A significantly low frequency of H. Pylori in gastric biopsies noted in non ulcer dyspepsia cases may be due to more frequent use of antibiotics and acid suppressant drugs used by general practitioners at some stage of disease. (author)

  8. The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon

    DEFF Research Database (Denmark)

    Krarup, A R; Abdel-Mohsen, M; Schleimann, M H

    2018-01-01

    to the change in integrated HIV DNA during MGN1703 treatment (P=0.020). In conclusion, MGN1703 induced a potent type I IFN response, without a concomitant general inflammatory response, in the intestines.Mucosal Immunology advance online publication, 02 August 2017; doi:10.1038/mi.2017.59....... and infectious diseases), led us to investigate the impact of MGN1703 (Lefitolimod) on intestinal homeostasis and viral persistence in HIV-positive individuals. Colonic sigmoid biopsies were collected (baseline and week four) from 11 HIV+ individuals on suppressive antiretroviral therapy, who received MGN1703...

  9. Cyclic GMP-AMP Displays Mucosal Adjuvant Activity in Mice

    OpenAIRE

    Škrnjug, Ivana; Guzmán, Carlos Alberto; Ruecker, Christine

    2014-01-01

    The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice....

  10. Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery

    Science.gov (United States)

    Hou, Lin; Shi, Yuyang; Jiang, Guixiang; Liu, Wei; Han, Huili; Feng, Qianhua; Ren, Junxiao; Yuan, Yujie; Wang, Yongchao; Shi, Jinjin; Zhang, Zhenzhong

    2016-08-01

    A safe and efficient nanocomposite hydrogel for colon cancer drug delivery was synthesized using pH-sensitive and biocompatible graphene oxide (GO) containing azoaromatic crosslinks as well as poly (vinyl alcohol) (PVA) (GO-N=N-GO/PVA composite hydrogels). Curcumin (CUR), an anti-cancer drug, was encapsulated successfully into the hydrogel through a freezing and thawing process. Fourier transform infrared spectroscopy, scanning electron microscopy and Raman spectroscopy were performed to confirm the formation and morphological properties of the nanocomposite hydrogel. The hydrogels exhibited good swelling properties in a pH-sensitive manner. Drug release studies under conditions mimicking stomach to colon transit have shown that the drug was protected from being released completely into the physiological environment of the stomach and small intestine. In vivo imaging analysis, pharmacokinetics and a distribution of the gastrointestinal tract experiment were systematically studied and evaluated as colon-specific drug delivery systems. All the results demonstrated that GO-N=N-GO/PVA composite hydrogels could protect CUR well while passing through the stomach and small intestine to the proximal colon, and enhance the colon-targeting ability and residence time in the colon site. Therefore, CUR loaded GO-N=N-GO/PVA composite hydrogels might potentially provide a theoretical basis for the treatment of colon cancer with high efficiency and low toxicity.

  11. Control of Colon Cancer Progression by the Colon Microbiome

    Science.gov (United States)

    2015-08-01

    Award  Number:    W81XWH-­14-­1-­0235   TITLE:      Control of Colon Cancer Progression by the Colon Microbiome PRINCIPAL  INVESTIGATOR:    Frank  J... Microbiome Table  of  Contents   Page   1. Introduction………………………………………………………….4 2. Keywords…………………………………………………………….5 3. Accomplishments………..…………………………………………5

  12. Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but not gelatinase activities.

    Science.gov (United States)

    Direito, Rosa; Lima, Ana; Rocha, João; Ferreira, Ricardo Boavida; Mota, Joana; Rebelo, Patrícia; Fernandes, Adelaide; Pinto, Rui; Alves, Paula; Bronze, Rosário; Sepodes, Bruno; Figueira, Maria-Eduardo

    2017-08-01

    Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging and antiinflammatory activities; however, little is known about the effects of persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Therefore, we aimed in this work to characterize the antiinflammatory and antiproliferative effects of a persimmon phenolic extract (80% acetone in water), using an in vivo model of experimental colitis and a model of cancer cell invasion. Our results show, for the first time, a beneficial effect of a persimmon phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells. Administration of persimmon phenolic extract to mice with TNBS-induced colitis led to a reduction in several functional and histological markers of colon inflammation, namely: attenuation of colon length decrease, reduction of the extent of visible injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate, reduction of mucosal hemorrhage and reduction of general histological features of colon inflammation. In vitro studies also showed that persimmon phenolic extract successfully impaired cell proliferation and invasion in HT-29 cells. Further investigation showed a decreased expression of COX-2 and iNOS in the colonic tissue of colitis mice, two important mediators of intestinal inflammation, but there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the role of inflammatory processes in the progression of CRC and the important link between inflammation and cancer, our results highlight the potential of persimmon polyphenols as a pharmacological tool in the treatment of patients with IBD. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Mucosal immunity and B cells in teleosts: effect of vaccination and stress.

    Directory of Open Access Journals (Sweden)

    David eParra

    2015-07-01

    Full Text Available Fish are subjected to several insults from the environment, which may endanger animal survival. Mucosal surfaces are the first line of defense against those threats and they act as a physical barrier to protect the animal but also function as immunologically active tissues. Thus, four mucosal-associated lymphoid tissues have been described in fish, which lead the immune responses in gut, skin, gills and nose. Humoral and cellular immunity, as well as its regulation and the factors that influence the response in these mucosal lymphoid tissues is still not well known in most of fish species. Mucosal B-lymphocytes and immunoglobulins (Igs are one of the key players in the immune response after vaccination. Recent findings about IgT in trout have delimited the compartmentalization of immune response in systemic and mucosal. The existence of IgT as a specialized mucosa Ig gives us the opportunity of measuring mucosal specific responses after vaccination, a fact that was not possible until recently in most of the fish species. Vaccination process is influenced by several factors, being stress one of the main stimuli determining the success of the vaccine. Thus, one of the major goals in a vaccination process is to avoid possible situations of stress, which might interfere with fish immune performance. However, the interaction between immune and neuroendocrine systems at mucosal tissues is still unknown. In this review we will summarized the latest findings about B-lymphocytes and immunoglobulins in mucosal immunity and the effect of stress and vaccines on B cell response at mucosal sites. It is important to point out that a small number of studies have been published regarding mucosal stress and very few about the influence of stress over mucosal B-lymphocytes.

  14. Study of reduction methods for irradiation on oral mucositis. The examination of reduction methods for mucosal failure

    International Nuclear Information System (INIS)

    Tonogi, Morio; Yamane, Genyuki; Aoyagi, Yutaka; Hasegawa, Azusa; Mizoe, Junetsu; Tsujii, Hirohiko

    2004-01-01

    Reduction methods for irradiation on oral mucosa examined concerning in acute phase of the carbon ion radiotherapy for head and neck malignancies. We enforced a mechanical teeth and gingival cleaning as an Oral hearth care and gargled a polaprezinc with sodium alginate, and azulene- lidocaine with glycerin sodium as a oral linces before radiation. The response of the mucosal failure was reduced compare with no care group. In this Result, we considered that oral hearth care for prevention of infection, and mucosa protection by the drug was important factor. (author)

  15. Transverse loop colostomy and colonic motility.

    Science.gov (United States)

    Pucciani, F; Ringressi, M N; Maltinti, G; Bechi, P

    2014-11-01

    The motility of the defunctionalized colon, distal to transverse loop colostomy, has never been studied "in vivo." The aim of our study was to evaluate the influence of transverse loop colostomy on colonic motility. Thirteen patients were examined before stoma closure by means of clinical evaluation and colonic manometry; we studied both the right and distal colon in both fasting and fed patients in order to detect motor activity. Quantitative and qualitative manometric analyses showed that the diverted colon had motor activity even if no regular colonic motor pattern was observed. The spreading of aboral propagated contractions (PCs) was sometimes recorded from the right colon to the distal colon. The response of the proximal and distal colon to a standard meal, when compared to fasting values, increased more than 40 and 35 %, respectively. Stool and gas ejections from the colostomy were never related to a particular type of colonic motility: Motor quiescence such as PCs was chaotically related to stool escape. In conclusion, motility of the defunctionalized colon is preserved in patients with transverse loop colostomy.

  16. Effect of entacapone on colon motility and ion transport in a rat model of Parkinson’s disease

    Science.gov (United States)

    Li, Li-Sheng; Liu, Chen-Zhe; Xu, Jing-Dong; Zheng, Li-Fei; Feng, Xiao-Yan; Zhang, Yue; Zhu, Jin-Xia

    2015-01-01

    AIM: To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson’s disease (PD) rats. METHODS: Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing. RESULTS: COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The β2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl- flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin. CONCLUSION: COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl- secretion in the PD rat. PMID:25834315

  17. Comparison of contrast media for visualization of the colon of healthy dogs during computed tomography and ultrasonography.

    Science.gov (United States)

    Cheon, Byunggyu; Moon, Sohyeon; Park, Seungjo; Lee, Sang-Kwon; Hong, Sunghwa; Cho, Hyun; Choi, Jihye

    2016-11-01

    OBJECTIVE To evaluate contrast agents for their ability to improve visualization of the colon wall and lumen during CT and ultrasonography. ANIMALS 10 healthy adult Beagles. PROCEDURES Food was withheld from dogs for 36 hours, after which dogs consumed 250 mL of polyethylene glycol solution. Dogs were then anesthetized, a contrast agent (tap water, diluted barium, or air; order randomly assigned) was administered rectally, iodine contrast medium (880 mg of I/kg) was administered IV, and CT and ultrasonography of the colon were performed. After a 1-week washout period, this process was repeated with a different contrast agent until all agents had been evaluated. Two investigators reviewed the CT and ultrasonographic images for colon wall thickness, conspicuity, artifacts, wall layering, and degree of lumen dilation at 4 sites. RESULTS Thickness of the colon wall was greatest in CT and ultrasonographic images with water used as contrast agent, followed by barium and then air. The CT images obtained after water administration had a smooth appearance that outlined the colonic mucosa and had the highest score of the 3 contrast agents for wall conspicuity. Although no substantial artifacts related to any of the contrast agents were identified on CT images, barium- and gas-induced shadowing and reverberation artifacts hindered wall evaluation during ultrasonography. For ultrasonography, the degree of conspicuity was highest with barium in the near-field wall and with water in the far-field wall. In contrast to CT, ultrasonography could be used to distinguish wall layering, and the mucosal and muscular layers were distinct with all contrast agents. CONCLUSIONS AND CLINICAL RELEVANCE Use of water as a contrast agent for both CT and ultrasonography of the colon in dogs compensated for each imaging modality's disadvantages and could be beneficial in the diagnosis of colon disease.

  18. Chronic ethanol consumption modulates growth factor release, mucosal cytokine production, and microRNA expression in nonhuman primates.

    Science.gov (United States)

    Asquith, Mark; Pasala, Sumana; Engelmann, Flora; Haberthur, Kristen; Meyer, Christine; Park, Byung; Grant, Kathleen A; Messaoudi, Ilhem

    2014-04-01

    Chronic alcohol consumption has been associated with enhanced susceptibility to both systemic and mucosal infections. However, the exact mechanisms underlying this enhanced susceptibility remain incompletely understood. Using a nonhuman primate model of ethanol (EtOH) self-administration, we examined the impact of chronic alcohol exposure on immune homeostasis, cytokine, and growth factor production in peripheral blood, lung, and intestinal mucosa following 12 months of chronic EtOH exposure. EtOH exposure inhibited activation-induced production of growth factors hepatocyte growth factor (HGF), granulocyte colony-stimulating factor (G-CSF), and vascular-endothelial growth factor (VEGF) by peripheral blood mononuclear cells (PBMC). Moreover, EtOH significantly reduced the frequency of colonic Th1 and Th17 cells in a dose-dependent manner. In contrast, we did not observe differences in lymphocyte frequency or soluble factor production in the lung of EtOH-consuming animals. To uncover mechanisms underlying reduced growth factor and Th1/Th17 cytokine production, we compared expression levels of microRNAs in PBMC and intestinal mucosa. Our analysis revealed EtOH-dependent up-regulation of distinct microRNAs in affected tissues (miR-181a and miR-221 in PBMC; miR-155 in colon). Moreover, we were able to detect reduced expression of the transcription factors STAT3 and ARNT, which regulate expression of VEGF, G-CSF, and HGF and contain targets for these microRNAs. To confirm and extend these observations, PBMC were transfected with either mimics or antagomirs of miR-181 and miR-221, and protein levels of the transcription factors and growth factors were determined. Transfection of microRNA mimics led to a reduction in both STAT3/ARNT as well as VEGF/HGF/G-CSF levels. The opposite outcome was observed when microRNA antagomirs were transfected. Chronic EtOH consumption significantly disrupts both peripheral and mucosal immune homeostasis, and this dysregulation may be

  19. Mucosal delivery of liposome-chitosan nanoparticle complexes.

    Science.gov (United States)

    Carvalho, Edison L S; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

    2009-01-01

    Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.

  20. Therapeutic management of radiation-induced oral mucositis

    International Nuclear Information System (INIS)

    Doerr, W.; Doelling-Jochem, I.; Baumann, M.; Herrmann, T.

    1997-01-01

    Background: Acute reactions of oral mucosa are a frequent side effect of radiotherapy, which often necessitates interruption of the treatment. Marked proliferation of tumor stem cells during treatment interruptions may occur in squamous cell carcinomata, which represent the majority of tumors in the head and neck area. Hence a fatal consequence of treatment breaks may be a significant decrease in tumor cure rates. Furthermore, marked acute responses frequently result in increased late sequelae ('consequential damage'). Therefore, amelioration of the mucosal response aiming at avoiding treatment breaks and at reduction of late reactions coul definitely increase the therapeutic success of radiation treatment. Results: A variety of prophylactic and therapeutic methods have been proposed for the management of acute radiation reactions of the oral mucosa. Frequently, their efficiacy has been established for chemotherapy or in combination with other immunosuppressive treatments. Hence, systemical rather than local effects have to be considered. Conclusions: In general, prophylaxis of oral mucositis is mainly based on dental restoration or edentation, in combination with frequent oral hygienic measures after the meals and with antiseptic mouthwashes. Intensive personal care is recommended. The necessity of a percutaneous endoscopic gastrostoma is dependent on the status of the patient and on size and localization of the treatment area, i.e. the impairment of food uptake which is to be expected. Therapeutic intervention is restricted to local or systemic treatment of pain and local application of antimycotics and antibiotics. (orig./VHE) [de

  1. Inlay buccal mucosal graft for reoperative posterior urethroplasty

    Directory of Open Access Journals (Sweden)

    Shou-Hung Tang

    2012-04-01

    Full Text Available Posterior urethral distraction injury following major pelvic trauma is a surgical challenge. Although rarely seen, cases of failure after formal urethral reconstruction are even more problematic. We adapted the concept of augmented free buccal mucosal grafts, which have been successful in anterior urethroplasty, for repairing the posterior urethra in these rare cases with the aim of reducing the likelihood of penile chordee postoperatively. During 2007–2009, four patients were candidates for the proposed procedure because they had received formal transperineal urethral reconstruction but were unable to urinate through the urethra. The urethra was approached transperineally and opened in the midline, rather than divided. Buccal mucosal grafts of an appropriate size were placed in the created urethral groove from 4- to 8 o’clock in the lithotomy view. After the procedure, the urethral catheter was kept for 3 weeks. All patients voided through the urethra after the procedure. The maximal postoperative urinary flow rates were between 12–15 ml/seconds in all cases for a follow-up period of 18–30 months. The recurrence rate was 50% (2/4. Recurrent strictures were minor, and they showed a web-like stricture ring near the suture line. Restricture within 6 months of surgery responded well to endoscopic internal urethrotomy plus dilatations. In conclusion, without further compromising urethral length, reoperative posterior urethroplasty with the inlay grafting technique can be considered in selective cases.

  2. Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

    Directory of Open Access Journals (Sweden)

    Ivana Škrnjug

    Full Text Available The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

  3. Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

    Science.gov (United States)

    Škrnjug, Ivana; Guzmán, Carlos Alberto; Rueckert, Christine; Ruecker, Christine

    2014-01-01

    The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

  4. Inlay buccal mucosal graft for reoperative posterior urethroplasty.

    Science.gov (United States)

    Tang, Shou-Hung; Kao, Chien-Chang; Wu, Seng-Tang; Meng, En; Cha, Tai-Lung

    2012-04-01

    Posterior urethral distraction injury following major pelvic trauma is a surgical challenge. Although rarely seen, cases of failure after formal urethral reconstruction are even more problematic. We adapted the concept of augmented free buccal mucosal grafts, which have been successful in anterior urethroplasty, for repairing the posterior urethra in these rare cases with the aim of reducing the likelihood of penile chordee postoperatively. During 2007-2009, four patients were candidates for the proposed procedure because they had received formal transperineal urethral reconstruction but were unable to urinate through the urethra. The urethra was approached transperineally and opened in the midline, rather than divided. Buccal mucosal grafts of an appropriate size were placed in the created urethral groove from 4- to 8 o'clock in the lithotomy view. After the procedure, the urethral catheter was kept for 3 weeks. All patients voided through the urethra after the procedure. The maximal postoperative urinary flow rates were between 12-15 ml/seconds in all cases for a follow-up period of 18-30 months. The recurrence rate was 50% (2/4). Recurrent strictures were minor, and they showed a web-like stricture ring near the suture line. Restricture within 6 months of surgery responded well to endoscopic internal urethrotomy plus dilatations. In conclusion, without further compromising urethral length, reoperative posterior urethroplasty with the inlay grafting technique can be considered in selective cases. Copyright © 2012. Published by Elsevier B.V.

  5. Pathogenesis of human papillomavirus-associated mucosal disease.

    Science.gov (United States)

    Groves, Ian J; Coleman, Nicholas

    2015-03-01

    Human papillomaviruses (HPVs) are a necessary cause of carcinoma of the cervix and other mucosal epithelia. Key events in high-risk HPV (HRHPV)-associated neoplastic progression include persistent infection, deregulated expression of virus early genes in basal epithelial cells and genomic instability causing secondary host genomic imbalances. There are multiple mechanisms by which deregulated virus early gene expression may be achieved. Integration of virus DNA into host chromosomes is observed in the majority of cervical squamous cell carcinomas (SCCs), although in ∼15% of cases the virus remains extrachromosomal (episomal). Interestingly, not all integration events provide a growth advantage to basal cervical epithelial cells or lead to increased levels of the virus oncogenes E6 and E7, when compared with episome-containing basal cells. The factors that provide a competitive advantage to some integrants, but not others, are complex and include virus and host contributions. Gene expression from integrated and episomal HRHPV is regulated through host epigenetic mechanisms affecting the virus long control region (LCR), which appear to be of functional importance. New approaches to treating HRHPV-associated mucosal neoplasia include knockout of integrated HRHPV DNA, depletion of virus transcripts and inhibition of virus early gene transcription through targeting or use of epigenetic modifiers. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. [Treatment and prevention of cancer treatment related oral mucositis].

    Science.gov (United States)

    Ruiz-Esquide, Gonzalo; Nervi, Bruno; Vargas, Alex; Maíz, Alberto

    2011-03-01

    One of the most common and troublesome complications of modern intensive anticancer treatments is oral mucositis. The purpose of this review is to summarize current evidence and clinical guidelines regarding its prevention and therapy. The use of keratinocyte growth factor-1, supplementary glutamine and other recently developed treatment modalities are discussed. The injury of the oral mucosa caused by antineoplastic agents promotes the local expression of multiple pro-inflammatory and pro-apoptotic molecules and eventually leads to the development of ulcers. Such lesions predispose patients to several infectious and nutritional complications. Also, they lead to modification of treatment schedules, potentially affecting overall prognosis. Local cryotherapy with ice chips and phototherapy with low energy laser may be useful as preventive measures. Mouthwashes with allopurinol and phototherapy with low energy laser can be used as treatment. In radiotherapy, special radiation administration techniques should be used to minimize mucosal injury. Pain control should always be optimized, with the use of patient controlled analgesia and topical use of morphine. Supplemental glutamine should not be used outside of research protocols. Lastly, thorough attention should be paid to general care and hygiene measures.

  7. Oral Mucosal Disorders in Pregnant versus Non-Pregnant Women

    Directory of Open Access Journals (Sweden)

    Fahimeh Rezazadeh

    2014-12-01

    Full Text Available The effects of pregnancy on the Oral Mucosa Disorder (OMD have been sporadically documented in some developed countries. Less known is the status of OMD during pregnancy in less developed/developing countries. Iran is no exception. This study assesses the prevalence of OMD in 200 pregnant women and compares the findings with the findings from a 200 non-pregnant woman of similar age distribution in Iran. The participants had been referred to a clinic to receive reproductive age-related services. Participants suffering from systemic chronic diseases, those on medications/drugs, smokers, needing biopsies, and those with urgent Oral Mucosal Lesion (OML treatments were excluded from the study. Oral mucosal of all 400 participants were examined. The participants’ age ranges were from 17 to 47; with the average age of 33.14 for one group; and 30.23 for the other group. Both groups had the same level of formal education. Out of 400 examined women; 62 had lesions, including 47 pregnant (23.5%; and 15 non-pregnant (7.5% women. This result shows that the OMD rate of occurrence was significantly higher among the pregnant women. Higher OML prevalence in pregnant women, as compared to the non-pregnant women, indicates the importance of timely oral examination of pregnant women and subsequent treatment plans for them.

  8. Specific extracellular matrix remodeling signature of colon hepatic metastases.

    Directory of Open Access Journals (Sweden)

    Maguy Del Rio

    Full Text Available To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment.

  9. Schwannoma of the sigmoid colon

    OpenAIRE

    Çakır, Tuğrul; Aslaner, Arif; Yaz, Müjgan; Gündüz, Umut rıza

    2015-01-01

    Colonic schwannomas are very rare gastrointestinal tumours originating from Schwann cells, which form the neural sheath. Primary schwannomas of the lower gastrointestinal tract are very rare and usually benign in nature. However, if they are not surgically removed, malign degeneration can occur. We report a case of a 79-year-old woman who presented to our clinic with rectal bleeding and constipation. She underwent a lower gastrointestinal tract endoscopy. A mass subtotally obstructing the lum...

  10. Oral yeast colonization throughout pregnancy

    OpenAIRE

    Rio, Rute; Sim?es-Silva, Liliana; Garro, Sofia; Silva, M?rio-Jorge; Azevedo, ?lvaro; Sampaio-Maia, Benedita

    2017-01-01

    Background Recent studies suggest that placenta may harbour a unique microbiome that may have origin in maternal oral microbiome. Although the major physiological and hormonal adjustments observed in pregnant women lead to biochemical and microbiological modifications of the oral environment, very few studies evaluated the changes suffered by the oral microbiota throughout pregnancy. So, the aim of our study was to evaluate oral yeast colonization throughout pregnancy and to compare it with n...

  11. Laxative effect of repeated Daiokanzoto is attributable to decrease in aquaporin-3 expression in the colon.

    Science.gov (United States)

    Kon, Risako; Yamamura, Miho; Matsunaga, Yukari; Kimura, Hiroshi; Minami, Moe; Kato, Saki; Ikarashi, Nobutomo; Sugiyama, Kiyoshi

    2018-03-01

    Daiokanzoto (DKT) exerts its laxative effect via colonic inflammation caused by sennoside A in Daio (rhubarb). Previously, we showed that the laxative effect of sennoside A is related to decreased aquaporin-3 (AQP3) expression in mucosal epithelial cells due to colonic inflammation. We also found that a combination of glycyrrhizin, an ingredient in Kanzo (glycyrrhiza), and sennoside A attenuates the inflammatory response induced by sennoside A and reduces its laxative effect. These findings indicate that DKT may be a long-term treatment for chronic constipation, but there is no evidence supporting this hypothesis. In this study, we analyzed the laxative effect of repeated DKT administration, focusing on AQP3 expression in the colon. After rats were treated for 7 days, decreased AQP3 expression and the onset of diarrhea were observed in the DKT group, but were not seen in the Daio group either. Although the relative abundance of gut microbiota after repeated DKT administration was similar to that after control treatment, Daio reduced Lactobacillaceae, Bifidobacteriaceae, and Bacteroidaceae levels and markedly increased Lachnospiraceae levels. In this study, we show that DKT has a sustained laxative effect, even upon repeated use, probably because it maintains decreased AQP3 expression and gut microbiota homeostasis. This outcome therefore indicates that DKT can be used as a long-term treatment for chronic constipation.

  12. Factors that mediate colonization of the human stomach by Helicobacter pylori.

    Science.gov (United States)

    Dunne, Ciara; Dolan, Brendan; Clyne, Marguerite

    2014-05-21

    Helicobacter pylori (H. pylori) colonizes the stomach of humans and causes chronic infection. The majority of bacteria live in the mucus layer overlying the gastric epithelial cells and only a small proportion of bacteria are found interacting with the epithelial cells. The bacteria living in the gastric mucus may act as a reservoir of infection for the underlying cells which is essential for the development of disease. Colonization of gastric mucus is likely to be key to the establishment of chronic infection. How H. pylori manages to colonise and survive in the hostile environment of the human stomach and avoid removal by mucus flow and killing by gastric acid is the subject of this review. We also discuss how bacterial and host factors may together go some way to explaining the susceptibility to colonization and the outcome of infection in different individuals. H. pylori infection of the gastric mucosa has become a paradigm for chronic infection. Understanding of why H. pylori is such a successful pathogen may help us understand how other bacterial species colonise mucosal surfaces and cause disease.

  13. Subepithelial myofibroblasts are novel nonprofessional APCs in the human colonic mucosa.

    Science.gov (United States)

    Saada, Jamal I; Pinchuk, Irina V; Barrera, Carlos A; Adegboyega, Patrick A; Suarez, Giovanni; Mifflin, Randy C; Di Mari, John F; Reyes, Victor E; Powell, Don W

    2006-11-01

    The human gastrointestinal mucosa is exposed to a diverse normal microflora and dietary Ags and is a common site of entry for pathogens. The mucosal immune system must respond to these diverse signals with either the initiation of immunity or tolerance. APCs are important accessory cells that modulate T cell responses which initiate and maintain adaptive immunity. The ability of APCs to communicate with CD4+ T cells is largely dependent on the expression of class II MHC molecules by the APCs. Using immunohistochemistry, confocal microscopy, and flow cytometry, we demonstrate that alpha-smooth muscle actin(+), CD90+ subepithelial myofibroblasts (stromal cells) constitutively express class II MHC molecules in normal colonic mucosa and that they are distinct from professional APCs such as macrophages and dendritic cells. Primary isolates of human colonic myofibroblasts (CMFs) cultured in vitro were able to stimulate allogeneic CD4+ T cell proliferation. This process was dependent on class II MHC and CD80/86 costimulatory molecule expression by the myofibroblasts. We also demonstrate that CMFs, engineered to express a specific DR4 allele, can process and present human serum albumin to a human serum albumin-specific and DR4 allele-restricted T cell hybridoma. These studies characterize a novel cell phenotype which, due to its strategic location and class II MHC expression, may be involved in capture of Ags that cross the epithelial barrier and present them to lamina propria CD4+ T cells. Thus, human CMFs may be important in regulating local immunity in the colon.

  14. Spontaneous perforation of sigmoid colon in a child with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Miolski Jelena

    2017-01-01

    Full Text Available Introduction. Perforation of the sigmoid colon is rare in children and its descriptions in medical literature are infrequent. Case Outline. In a 13-year-old boy with acute lymphoblastic leukemia, a ten-month course of chemotherapy was accompanied by many complications: parasitic infestation (Enterobius vermicularis, lung candidiasis, esophageal candidiasis, steroid diabetes, anaphylactoid reaction to L-asparaginase, febrile neutropenia, mucositis, anemia, thrombocytopenia, enterocolitis, and respiratory distress syndrome. During reinduction treatment, consisting of dexamethasone, vincristine, doxorubicin, and crisantaspase, he complained of abdominal pain and, upon radiographic examination, was found to have pneumoperitoneum. Because of suspicion of abdominal hollow organ perforation, he was subjected to explorative laparotomy, which yielded the diagnosis of perforation of the sigmoid colon. Conclusion. After an extensive review of the published reports on sigmoid perforation, all associated conditions that could possibly induce perforation – such as Hirschsprung’s disease or foreign body – were systematically excluded in our patient. Although typhlitis was the first diagnostic hypothesis, this was excluded by intraoperative findings, histopathology, and perforation site. To the best of our knowledge, this is the first report of a spontaneous perforation of the sigmoid colon in a child with acute lymphoblastic leukemia.

  15. Clostridium septicum Gas Gangrene in Colon Cancer: Importance of Early Diagnosis

    Directory of Open Access Journals (Sweden)

    Sowmya Nanjappa

    2015-01-01

    Full Text Available The Clostridia species are responsible for some of the deadliest diseases including gas gangrene, tetanus, and botulism. Clostridium septicum is a rare subgroup known to cause atraumatic myonecrosis and is associated with colonic malignancy or immunosuppression. It is a Gram-positive, anaerobic, spore-forming bacillus found in the gastrointestinal tract and can lead to direct, spontaneous infections of the bowel and peritoneal cavity. The anaerobic glycolysis of the tumor produces an acidic, hypoxic environment favoring germination of clostridial spores. Tumor-induced mucosal ulceration allows for translocation of sporulated bacteria from the bowel into the bloodstream, leading to fulminant sepsis. C. septicum bacteremia can have a variable presentation and is associated with greater than 60% mortality rate. The majority of deaths occur within the first 24 hours if diagnosis and appropriate treatment measures are not promptly started. We report a case of abdominal myonecrosis in a patient with newly diagnosed colon cancer. The aim of this study is to stress the importance of maintaining a high suspicion of C. septicum infection in patients with underlying colonic malignancy.

  16. Oral yeast colonization throughout pregnancy.

    Science.gov (United States)

    Rio, R; Simões-Silva, L; Garro, S; Silva, M-J; Azevedo, Á; Sampaio-Maia, B

    2017-03-01

    Recent studies suggest that placenta may harbour a unique microbiome that may have origin in maternal oral microbiome. Although the major physiological and hormonal adjustments observed in pregnant women lead to biochemical and microbiological modifications of the oral environment, very few studies evaluated the changes suffered by the oral microbiota throughout pregnancy. So, the aim of our study was to evaluate oral yeast colonization throughout pregnancy and to compare it with non-pregnant women. The oral yeast colonization was assessed in saliva of 30 pregnant and non-pregnant women longitudinally over a 6-months period. Demographic information was collected, a non-invasive intra-oral examination was performed and saliva flow and pH were determined. Pregnant and non-pregnant groups were similar regarding age and level of education. Saliva flow rate did not differ, but saliva pH was lower in pregnant than in non-pregnant women. Oral yeast prevalence was higher in pregnant than in non-pregnant women, either in the first or in the third trimester, but did not attain statistical significance. In individuals colonized with yeast, the total yeast quantification (Log10CFU/mL) increase from the 1st to the 3rd trimester in pregnant women, but not in non-pregnant women. Pregnancy may favour oral yeast growth that may be associated with an acidic oral environment.

  17. CT staging of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dighe, S. [Department of Radiology, Royal Marsden Hospital, Sutton SM5 2TT (United Kingdom); Swift, I. [Department of Surgery, Mayday University Hospital, Croydon CR7 7YE (United Kingdom); Brown, G. [Department of Radiology, Royal Marsden Hospital, Sutton SM5 2TT (United Kingdom)], E-mail: gina.brown@rmh.nhs.uk

    2008-12-15

    Computer tomography (CT) has been the principal investigation in the staging of colon cancers. The information obtained with routine CT has been limited to identifying the site of the tumour, size of the tumour, infiltration into surrounding structures and metastatic spread. The Foxtrot trial National Cancer Research Institute (NCRI) has been specifically designed to evaluate the efficacy of neoadjuvant treatment in colon cancers by using preoperative chemotherapy with or without an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody to improve outcome in high-risk operable colon cancer. Patients are selected based on their staging CT examination. The criteria for poor prognosis are T4 and T3 tumours with more than 5 mm extramural depth. Thus the success of the trial would depend upon the confidence of the radiologist to identify the patients that would receive the neoadjuvant treatment. The aim of this review is to explain the process of identifying high-risk features seen on the staging CT images. This will help to identify a cohort of patients that could truly benefit from neoadjuvant strategies.

  18. CT staging of colon cancer

    International Nuclear Information System (INIS)

    Dighe, S.; Swift, I.; Brown, G.

    2008-01-01

    Computer tomography (CT) has been the principal investigation in the staging of colon cancers. The information obtained with routine CT has been limited to identifying the site of the tumour, size of the tumour, infiltration into surrounding structures and metastatic spread. The Foxtrot trial National Cancer Research Institute (NCRI) has been specifically designed to evaluate the efficacy of neoadjuvant treatment in colon cancers by using preoperative chemotherapy with or without an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody to improve outcome in high-risk operable colon cancer. Patients are selected based on their staging CT examination. The criteria for poor prognosis are T4 and T3 tumours with more than 5 mm extramural depth. Thus the success of the trial would depend upon the confidence of the radiologist to identify the patients that would receive the neoadjuvant treatment. The aim of this review is to explain the process of identifying high-risk features seen on the staging CT images. This will help to identify a cohort of patients that could truly benefit from neoadjuvant strategies

  19. Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate Has Immunomodulatory Effects on the Colon of Mice that Spontaneously Develop Colitis.

    Directory of Open Access Journals (Sweden)

    Anna Pérez-Bosque

    Full Text Available Dietary immunoglobulin concentrates prepared from animal plasma can modulate the immune response of gut-associated lymphoid tissue (GALT. Previous studies have revealed that supplementation with serum-derived bovine immunoglobulin/protein isolate (SBI ameliorates colonic barrier alterations in the mdr1a-/- genetic mouse model of IBD. Here, we examine the effects of SBI on mucosal inflammation in mdr1a-/- mice that spontaneously develop colitis. Wild type (WT mice and mice lacking the mdr1a gene (KO were fed diets supplemented with either SBI (2% w/w or milk proteins (Control diet, from day 21 (weaning until day 56. Leucocytes in mesenteric lymph nodes (MLN and in lamina propria were determined, as was mucosal cytokine production. Neutrophil recruitment and activation in MLN and lamina propria of KO mice were increased, but were significantly reduced in both by SBI supplementation (p < 0.05. The increased neutrophil recruitment and activation observed in KO mice correlated with increased colon oxidative stress (p < 0.05 and SBI supplementation reduced this variable (p < 0.05. The Tact/Treg lymphocyte ratios in MLN and lamina propria were also increased in KO animals, but SBI prevented these changes (both p < 0.05. In the colon of KO mice, there was an increased production of mucosal pro-inflammatory cytokines such as IL-2 (2-fold, IL-6 (26-fold and IL-17 (19-fold, and of chemokines MIP-1β (4.5-fold and MCP-1 (7.2-fold. These effects were significantly prevented by SBI (p < 0.05. SBI also significantly increased TGF-β secretion in the colon mucosa, suggesting a role of this anti-inflammatory cytokine in the modulation of GALT and the reduction of the severity of the inflammatory response during the onset of colitis.

  20. Absorption of iron in the aged; investigation of mucosal-uptake, mucosal-transfer and retention of a physiological dose of inorganic iron

    International Nuclear Information System (INIS)

    Marx, J.J.M.

    1976-01-01

    Iron (II) and iron (III) uptake by the mucosal cells, the retention in the body, and the mucosal-transport fraction were studied in 40 healthy people over 65 years old, in 30 young adults and in 20 patients with iron-deficiency. The study was performed with 59 Fe as a tracer and 51 Cr as an inert indicator. The radioactivity was measured with a whole body scanner 24 hours and 24 days after ingestion

  1. Adrenergic influence on gastric mucosal blood flow in gastric fistula dogs

    DEFF Research Database (Denmark)

    Hovendal, C P; Bech, K; Gottrup, F

    1984-01-01

    micrograms/kg/min) induced an increase in mucosal blood flow and a similar increase in acid secretion. If the dopamine infusion was preceded by alpha-receptor blockade, a pronounced increase in mucosal blood flow was observed without a similar increase in acid secretion. beta-adrenergic stimulation...

  2. Use of inactivated E.Coli enterotoxins to enhance respiratory mucosal adjuvanticity during vaccination in swine

    Science.gov (United States)

    In order to augment responses to respiratory vaccines in swine, various adjuvants were intranasally co-administered with an antigen to pigs. Detoxified E. coli enterotoxins LTK63 and LTR72 enhanced mucosal and systemic immunity to the model peptide, exhibiting their efficacy as mucosal adjuvants for...

  3. Oral mucositis in patients treated with chemotherapy for solid tumors: a retrospective analysis of 150 cases

    NARCIS (Netherlands)

    Raber-Durlacher, J. E.; Weijl, N. I.; Abu Saris, M.; de Koning, B.; Zwinderman, A. H.; Osanto, S.

    2000-01-01

    The incidence and the severity of chemotherapy-associated oral mucositis were determined in a retrospective analysis of 150 patients with various solid tumors. In addition, possible risk factors for the development of mucositis were identified. Patients were treated with chemotherapeutic regimens

  4. Host responses to Candida albicans: Th17 cells and mucosal candidiasis

    OpenAIRE

    Conti, Heather R.; Gaffen, Sarah L.

    2010-01-01

    Candida albicans causes mucosal and disseminated candidiasis, which represent serious problems for the rapidly expanding immunocompromised population. Until recently, Th1-mediated immunity was thought to confer the primary protection, particularly for oral candidiasis. However, emerging data indicate that the newly-defined Th17 compartment appears to play the predominant role in mucosal candidiasis.

  5. The Potential Effect of Oral Microbiota in the Prediction of Mucositis During Radiotherapy for Nasopharyngeal Carcinoma

    Directory of Open Access Journals (Sweden)

    Xiao-Xia Zhu

    2017-04-01

    Interpretation: Oral microbiota changes correlate with the progression and aggravation of radiotherapy-induced mucositis in patients with nasopharyngeal carcinoma. Microbiota-based strategies can be used for the early prediction and prevention of the incidence of severe mucositis during radiotherapy.

  6. Mucosal immune response in broilers following vaccination with inactivated influenza and recombinant Bacillus subtilis

    Science.gov (United States)

    Mucosal and systemic immunity were observed in broilers vaccinated with mannosylated chitosan adjuvated (MCA) inactivated A/Turkey/Virginia/158512/2002 (H7N2) and administered with and without recombinant Bacillus subtilis to elicit heterologous influenza strain protection. Previously, mucosal immu...

  7. Clinical effects of flurbiprofen tooth patch on radiation-induced oral mucositis. A pilot study

    NARCIS (Netherlands)

    Stokman, MA; Spijkervet, FKL; Burlage, FR; Roodenburg, JLN

    Background: Mucositis is an oral sequela of radiotherapy. In the development of mucositis several mechanisms play a role, such as inflammation and the effect of radiation on the high proliferation rate of oral basal epithelial cells. Therefore, administration of a drug with antiinflammatory and

  8. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy

    NARCIS (Netherlands)

    Lalla, Rajesh V.; Bowen, Joanne; Barasch, Andrei; Elting, Linda; Epstein, Joel; Keefe, Dorothy M.; McGuire, Deborah B.; Migliorati, Cesar; Nicolatou-Galitis, Ourania; Peterson, Douglas E.; Raber-Durlacher, Judith E.; Sonis, Stephen T.; Elad, Sharon; Al-Dasooqi, Noor; Brennan, Michael; Gibson, Rachel; Fulton, Janet; Hewson, Ian; Jensen, Siri B.; Logan, Richard; Öhrn, Kerstin E. O.; Sarri, Triantafyllia; Saunders, Deborah; von Bültzingslöwen, Inger; Yarom, Noam

    2014-01-01

    Mucositis is a highly significant, and sometimes dose-limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for mucositis.

  9. Systematic review of agents for the management of gastrointestinal mucositis in cancer patients

    NARCIS (Netherlands)

    Gibson, Rachel J.; Keefe, Dorothy M. K.; Lalla, Rajesh V.; Bateman, Emma; Blijlevens, Nicole; Fijlstra, Margot; King, Emily E.; Stringer, Andrea M.; van der Velden, Walter J. F. M.; Yazbeck, Roger; Elad, Sharon; Bowen, Joanne M.

    The aim of this study was to review the available literature and define clinical practice guidelines for the use of agents for the prevention and treatment of gastrointestinal mucositis. A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive

  10. Systematic review of agents for the management of gastrointestinal mucositis in cancer patients.

    NARCIS (Netherlands)

    Gibson, R.J.; Keefe, D.M.; Lalla, R.V.; Bateman, E.; Blijlevens, N.M.; Fijlstra, M.; King, E.E.; Stringer, A.M.; Velden, W.J.F.M. van der; Yazbeck, R.; Elad, S.; Bowen, J.M.

    2013-01-01

    PURPOSE: The aim of this study was to review the available literature and define clinical practice guidelines for the use of agents for the prevention and treatment of gastrointestinal mucositis. METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association

  11. Treatment of Helicobacter pylori infection favourably affects gastric mucosal superoxide dismutases

    NARCIS (Netherlands)

    Götz, J. M.; Thio, J. L.; Verspaget, H. W.; Offerhaus, G. J.; Biemond, I.; Lamers, C. B.; Veenendaal, R. A.

    1997-01-01

    Excessive production of reactive oxygen metabolites (ROMs) by phagocytic cells is thought to contribute to the mucosal pathology of Helicobacter pylori infection. Previously, H pylori infection was shown to have a differential effect on some gastric mucosal scavenger enzymes of ROMs-namely,

  12. The role of sucralfate oral suspension in prevention of radiation induced mucositis

    Directory of Open Access Journals (Sweden)

    Hamid Emami

    2008-12-01

    Full Text Available

    • BACKGROUND: Mucositis is one of the most common complications of radiotherapy in head and neck cancers. The aim of this study was to evaluate sucralfate mouthwash in prevention of radiation induced mucositis.
    • METHODS: A clinical randomized trial performed on 52 patients with head and neck cancers in Sayyed-Al-Shohada Hospital of Isfahan University of Medical Sciences. These patients randomly assigned in 2 groups of 26 patients. Placebo and sucralfate was used for control and experimental patients respectiv ly, from the beginning of radiotherapy. Patients were visited weekly until the end of treatment. Grade of the mucositis was evaluated according to WHO grading scale.
    • RESULTS: Sucralfate significantly reduced the mean grade of mucositis in weeks one to four (with P-values of 0.02, 0.02, 0.001 and 0.004, respectively. Development of grade3 mucositis was also lower in sucralfate group (P-value = 0.0001. But, time interval between radiotherapy and appearance of mucositis was not statistically different in the two groups (P-value = 0.9
    • CONCLUSIONS: This study indicated that using oral suspension of sucralfate reduced the grade of radiation-induced mucositis, but did not prevent or delay it.
    • KEYWORDS: Mucositis, radiotherapy, sucralfate, head and neck cancers.

  13. Icing oral mucositis: Oral cryotherapy in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant.

    Science.gov (United States)

    Chen, Joey; Seabrook, Jamie; Fulford, Adrienne; Rajakumar, Irina

    2017-03-01

    Background Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high-dose melphalan conditioning chemotherapy. Oral cryotherapy has been documented to be potentially effective in reducing oral mucositis. The aim of this study was to examine the effectiveness of the cryotherapy protocol implemented within the hematopoietic stem cell transplant program. Methods A retrospective chart review was conducted of adult multiple myeloma patients who received high-dose melphalan conditioning therapy for autologous hematopoietic stem cell transplant. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints included duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition use. Results One hundred and forty patients were included in the study, 70 patients in both no cryotherapy and cryotherapy groups. Both oral mucositis incidence and severity were found to be significantly lower in the cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy compared to 67 (95.7%) in the no cryotherapy group (p cryotherapy group (p = 0.03). Oral mucositis duration and use of parenteral narcotics were also significantly reduced. Duration of hospital stay and use of parenteral nutrition were similar between the two groups. Conclusion The cryotherapy protocol resulted in a significantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inexpensive and generally well-tolerated practice.

  14. Understanding the Oral Mucosal Absorption and Resulting Clinical Pharmacokinetics of Asenapine

    NARCIS (Netherlands)

    Bartlett, Jeremy A.; Maarschalk, Kees van der Voort

    2012-01-01

    Absorption of drugs from the oral cavity into the mucosal tissues is typically a fast event. Dissolved drugs partition into the mucosal membranes and within minutes will reach equilibrium with drug in solution in the oral cavity. However, this does not always equate to rapid drug appearance in the

  15. Novel mucosal DNA-MVA HIV vaccination in which DNA-IL-12 plus Cholera Toxin B subunit (CTB) cooperates to enhance cellular systemic and mucosal genital tract immunity

    OpenAIRE

    Maeto, Cynthia Alejandra; Rodríguez, Ana María; Holgado, María Pía; Falivene, Juliana; Gherardi, Maria Magdalena

    2017-01-01

    Induction of local antiviral immune responses at the mucosal portal surfaces where HIV-1 and other viral pathogens are usually first encountered remains a primary goal for most vaccines against mucosally acquired viral infections. Exploring mucosal immunization regimes in order to find optimal vector combinations and also appropriate mucosal adjuvants in the HIV vaccine development is decisive. In this study we analyzed the interaction of DNA-IL-12 and cholera toxin B subunit (CTB) after thei...

  16. A prospective comparison of common toxicity criteria adverse events Version 3 and 4 in assessing oral mucositis for oral and oropharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    M. Hickman

    2017-03-01

    Conclusion: Differences in grading of mucositis scored by V3 and V4 are frequent. Relationships between biologically effective dose and rates of grade 3 mucositis have historically been based on mucosal appearances. It is not known whether the same relationships apply when mucositis is graded based on symptomatic grading systems. Both V3 and V4 should be used in clinical trials to improve understanding of mucositis and its relationship to quality of life and late mucosal toxicity.

  17. Clinical, biological, histological features and treatment of oral mucositis induced by radiation therapy: a literature review

    International Nuclear Information System (INIS)

    Bonan, Paulo Rogerio Ferreti; Lopes, Marcio Ajudarte; Almeida, Oslei Paes de; Alves, Fabio de Abreu

    2005-01-01

    The oral mucositis is a main side effect of radiotherapy on head and neck, initiating two weeks after the beginning of the treatment. It is characterized by sensation of local burning to intense pain, leading in several cases, to the interruption of the treatment. The purpose of this work is to review the main published studies that discuss the clinical, biological and histopathological features of oral mucositis induced by radiation therapy and to describe the main approaches recommended to prevent or to treat it. Although the clinical features of mucositis are intensively described in the literature, few studies address the histopathological alterations in oral mucositis and only recently, its biological processes have been investigated. The biological mechanisms involved in the radiation tissue damage have been only recently discussed and there is no consensus among treatment modalities. Yet, the progressive knowledge in the histopathology and biological characteristics of oral mucositis probably will lead to more effective in prevention and control strategies. (author)

  18. Glucagon-like peptide-1 as a treatment for chemotherapy-induced mucositis

    DEFF Research Database (Denmark)

    Kissow, Hannelouise; Hartmann, Bolette; Holst, Jens Juul

    2012-01-01

    : To determine whether endogenous GLP-1 contributes to the healing processes and if exogenous GLP-1 has a potential role in treating mucositis. METHODS: Mice were injected with 5-fluorouracil (5-FU) or saline to induce mucositis and were then treated with GLP-1, GLP-2, GLP-2 (3-33), exendin (9-39) or vehicle....... The mice were sacrificed 48 or 96 h after the 5-FU injections. The end points were intestinal weight, villus height, proliferation and histological scoring of mucositis severity. Rats were injected with 5-FU or saline, and after 48 h, blood was drawn and analysed for GLP-1 and GLP-2 concentration. RESULTS......: GLP-1 and GLP-2 significantly prevented the loss of mucosal mass and villus height and significantly decreased the mucositis severity score in the duodenum and jejunum 48 h after chemotherapy. The effect was equivalent. Exendin (9-39) reduced the intestinal weight 96 h after chemotherapy. The GLP-1...

  19. Pilot study of ice-ball cryotherapy for radiation-induced oral mucositis

    Energy Technology Data Exchange (ETDEWEB)

    Ohyama, Waichiro; Ebihara, Satoshi [National Cancer Center Hospital, Tokyo (Japan)

    1996-02-01

    Oral mucositis caused by radiotherapy is intractable and may worsen the patient`s nutritional condition and interrupt treatment. To reduce the incidence and severity of oral mucositis induced by cancer therapy and promote early improvement of its symptoms, we devised cryotherapy by ice balls using Elase (fibrinolysin and deoxyribonuclease, combined). The therapeutic effect of ice-ball cryotherapy was evaluated in 10 patients with carcinoma of the oral cavity and pharynx who were undergoing radiotherapy. Cryotherapy was continued from the development of oral mucositis until its disappearance. The severity of various symptoms of mucositis were reduced by cryotherapy. Healing required 3 to 16 days (median, 7 days) after the end of radiotherapy. Radiotherapy was not interrupted in any cases. This preliminary report suggests that ice-ball cryotherapy is an effective treatment for radiation-induced oral mucositis. (author).

  20. Pilot study of ice-ball cryotherapy for radiation-induced oral mucositis

    International Nuclear Information System (INIS)

    Ohyama, Waichiro; Ebihara, Satoshi

    1996-01-01

    Oral mucositis caused by radiotherapy is intractable and may worsen the patient's nutritional condition and interrupt treatment. To reduce the incidence and severity of oral mucositis induced by cancer therapy and promote early improvement of its symptoms, we devised cryotherapy by ice balls using Elase (fibrinolysin and deoxyribonuclease, combined). The therapeutic effect of ice-ball cryotherapy was evaluated in 10 patients with carcinoma of the oral cavity and pharynx who were undergoing radiotherapy. Cryotherapy was continued from the development of oral mucositis until its disappearance. The severity of various symptoms of mucositis were reduced by cryotherapy. Healing required 3 to 16 days (median, 7 days) after the end of radiotherapy. Radiotherapy was not interrupted in any cases. This preliminary report suggests that ice-ball cryotherapy is an effective treatment for radiation-induced oral mucositis. (author)

  1. Improved mucoadhesion and cell uptake of chitosan and chitosan oligosaccharide surface-modified polymer nanoparticles for mucosal delivery of proteins.

    Science.gov (United States)

    Dyawanapelly, Sathish; Koli, Uday; Dharamdasani, Vimisha; Jain, Ratnesh; Dandekar, Prajakta

    2016-08-01

    The main aim of the present study was to compare mucoadhesion and cellular uptake efficiency of chitosan (CS) and chitosan oligosaccharide (COS) surface-modified polymer nanoparticles (NPs) for mucosal delivery of proteins. We have developed poly (D, L-lactide-co-glycolide) (PLGA) NPs, surface-modified COS-PLGA NPs and CS-PLGA NPs, by using double emulsion solvent evaporation method, for encapsulating bovine serum albumin (BSA) as a model protein. Surface modification of NPs was confirmed using physicochemical characterization methods such as particle size and zeta potential, SEM, TEM and FTIR analysis. Both surface-modified PLGA NPs displayed a slow release of protein compared to PLGA NPs. Furthermore, we have explored the mucoadhesive property of COS as a material for modifying the surface of polymeric NPs. During in vitro mucoadhesion test, positively charged COS-PLGA NPs and CS-PLGA NPs exhibited enhanced mucoadhesion, compared to negatively charged PLGA NPs. This interaction was anticipated to improve the cell interaction and uptake of NPs, which is an important requirement for mucosal delivery of proteins. All nanoformulations were found to be safe for cellular delivery when evaluated in A549 cells. Moreover, intracellular uptake behaviour of FITC-BSA loaded NPs was extensively investigated by confocal laser scanning microscopy and flow cytometry. As we hypothesized, positively charged COS-PLGA NPs and CS-PLGA NPs displayed enhanced intracellular uptake compared to negatively charged PLGA NPs. Our results demonstrated that CS- and COS-modified polymer NPs could be promising carriers for proteins, drugs and nucleic acids via nasal, oral, buccal, ocular and vaginal mucosal routes.

  2. Decreased colonization of fecal Clostridium coccoides/Eubacterium rectale species from ulcerative colitis patients in an in vitro dynamic gut model with mucin environment.

    Science.gov (United States)

    Vermeiren, Joan; Van den Abbeele, Pieter; Laukens, Debby; Vigsnaes, Louise Kristine; De Vos, Martine; Boon, Nico; Van de Wiele, Tom

    2012-03-01

    The mucus layer in the colon, acting as a barrier to prevent invasion of pathogens, is thinner and discontinuous in patients with ulcerative colitis (UC). A recent developed in vitro dynamic gut model, the M-SHIME, was used to compare long-term colonization of the mucin layer by the microbiota from six healthy volunteers (HV) and six UC patients and thus distinguish the mucin adhered from the luminal microbiota. Although under the same nutritional conditions, short-chain fatty acid production by the luminal communities from UC patients showed a tendency toward a lower butyrate production. A more in-depth community analysis of those microbial groups known to produce butyrate revealed that the diversity of the Clostridium coccoides/Eubacterium rectale and Clostridium leptum group, and counts of Faecalibacterium prausnitzii were lower in the luminal fractions of the UC samples. Counts of Roseburia spp. were lower in the mucosal fractions of the UC samples. qPCR analysis for butyryl-CoA:acetate CoA transferase, responsible for butyrate production, displayed a lower abundance in both the luminal and mucosal fractions of the UC samples. The M-SHIME model revealed depletion in butyrate producing microbial communities not restricted to the luminal but also in the mucosal samples from UC patients compared to HV. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  3. Prophylactic clipping for the prevention of bleeding following wide-field endoscopic mucosal resection of laterally spreading colorectal lesions: an economic modeling study.

    Science.gov (United States)

    Bahin, Farzan F; Rasouli, Khalid N; Williams, Stephen J; Lee, Eric Y T; Bourke, Michael J

    2016-08-01

    Clinically significant bleeding (CSPEB) is the most common adverse event following endoscopic mucosal resection (EMR) of large sessile and laterally spreading colorectal lesions (LSLs), and is associated with morbidity and resource utilization. CSPEB occurs more frequently with proximal LSLs. Prophylactic clipping of the post-EMR defect may be beneficial in CSPEB prevention. The aim of this study was to determine the cost-effectiveness of a prophylactic clipping strategy. We hypothesized that prophylactic clipping in the proximal colon was cost-effective. An economic model was applied to outcomes from the Australian Colonic Endoscopic Mucosal Resection (ACE) Study. Clip distances of 3, 5, 8, and 10 mm were analyzed. The cost of treating CSPEB was determined from an independent costing agency. The funds needed to spend (FNS) was the cost incurred in order to prevent one episode of CSPEB. A break-even analysis was performed to determine cost equivalence of the costs of clipping and CSPEB. Outcomes of 1717 LSLs (mean size 35.8 mm; 52.6 % proximal colon) that underwent EMR were analyzed. The overall rate of CSPEB was 6.4 % (proximal 8.9 %; distal 3.7 %). Endoscopic management was required in 45 % of CSPEB episodes. With a clip distance of 3 mm, the expected cost of prophylactic clipping was € 1106 per lesion compared with € 157 per lesion for the expected cost of CSPEB without clipping. At 100 % clipping efficacy, the FNS was € 14 826 (proximal and distal lesions € 9309 and € 29 540, respectively). A clip price of € 10.35 was required for the cost of clipping to offset the cost of CSPEB. A prophylactic clipping strategy is not cost-effective and at present cannot be justified for all lesions or selectively for lesions in the proximal colon. ClinicalTrials.gov (NCT01368289). © Georg Thieme Verlag KG Stuttgart · New York.

  4. The therapeutic effect of PLAG against oral mucositis in hamster and mouse model

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    Ha-Reum Lee

    2016-10-01

    Full Text Available Chemotherapy-induced mucositis can limit the effectiveness of cancer therapy and increase the risk of infections. However, no specific therapy for protection against mucositis is currently available. In this study, we investigated the therapeutic effect of PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride in 5-fluorouracil (5-FU-induced oral mucositis animal models. Hamsters were administered 5-FU (80 mg/kg intraperitoneally on days 0, 6, and 9. The animals’ cheek pouches were then scratched equally with the tip of an 18-gauge needle on days 1, 2, and 7. PLAG was administered daily at 250 mg/kg/day. PLAG administration significantly reduced 5-FU/scratching–induced mucositis. Dramatic reversal of weight loss in PLAG-treated hamsters with mucositis was observed. Histochemical staining data also revealed newly differentiated epidermis and blood vessels in the cheek pouches of PLAG-treated hamsters, indicative of recovery. Whole blood analyses indicated that PLAG prevents 5-FU–induced excessive neutrophil transmigration to the infection site and eventually stabilizes the number of circulating neutrophils. In a mouse mucositis model, mice with 5-FU–induced disease treated with PLAG exhibited resistance to body-weight loss compared with mice that received 5-FU or 5-FU/scratching alone. PLAG also dramatically reversed mucositis-associated weight loss and inhibited mucositis-induced inflammatory responses in the tongue and serum. These data suggest that PLAG enhances recovery from 5-FU–induced oral mucositis and may therefore be a useful therapeutic agent for treating side effects of chemotherapy, such as mucositis and cachexia.

  5. Sequential changes in luminal microflora and mucosal cytokine expression during developing of colitis in HLA-B27/beta2-microglobulin transgenic rats.

    Science.gov (United States)

    Hata, K; Andoh, A; Sato, H; Araki, Y; Tanaka, M; Tsujikawa, T; Fujiyama, Y; Bamba, T

    2001-11-01

    Transgenic rats expressing HLA-B27 and human beta2-microglobulin (HLA-B27 rats) spontaneously develop chronic colitis resembling human inflammatory bowel disease. We investigated the sequential changes in the luminal bacterial flora and mucosal cytokine mRNA expression in this model. HLA-B27 rats were maintained in a specific pathogen-free environment, and luminal microflora was evaluated by standard bacterial culture technique. The expression of mucosal cytokine mRNA was analysed by RT-PCR methods. Clinical symptoms of colitis appeared at 8 weeks of age. The total number of obligate anaerobes was higher than those of facultative anaerobes during the experimental period. At 6 weeks of age, the colonization of Bacteroides spp., Bifidobacterium spp. and Lactobacillus spp. was already detectable at high concentrations, whereas Clostridium spp. and Eubacterium spp. were not detected. The expression of proinflammatory cytokines (IL-Ibeta, IL-8 and TNF-alpha) appeared at 8 weeks of age, and these were detectable until 17 weeks. A similar pattern was observed in the expression of Th1 cytokines (IL-2, IL-12 and IFN-gamma). On the other hand, the expression of Th2 cytokines (IL-4, IL-10 and TGF-beta) was weak. IL-4 mRNA expression was weakly detectable only at 6 and 8 weeks of age. The expression of IL-10 and TGF-beta mRNA was scarcely detectable throughout the experimental period. The development of colitis may be mediated by both the predominant expression of Th1 cytokines and the weakness of Th2 cytokine expression in the mucosa. The colonization of anaerobic bacteria, especially Bacteroides spp., may be initiating and promoting these cytokine responses.

  6. Fabrication and Evaluation of Tinidazole Microbeads for Colon Targeting

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    Amit K. Pandey

    2012-05-01

    Full Text Available Objective: The purpose of present investigation was to develop and evaluate multiparticulate system exploiting pH-sensitive property and specific biodegradability of calcium alginate microbeads, for colon- targeted delivery of Tinidazole for the treatment of amoebic colitis. Methods: Calcium alginate beads containing Tinidazole were prepared by ionotropic gelation technique followed by coating with Eudragit S100 using solvent evaporation method to obtain pH sensitive microbeads. Various formulation parameters were optimized which included concentration of sodium alginate (2% w/v, curing time (20 min and concentration of pectin (1% w/ v. All the formulations were evaluated for surface morphology, particle size analysis, entrapment efficiency and in-vitro drug release in conditions simulating colonic fluid in the presence of rat caecal (2% w/v content. Results: The average size of beads of optimized formulation (FT4 was found to be 998.73依5.12 毺 m with entrapment efficiency of 87.28依2.19 %. The invitro release of Eudragit S100 coated beads in presence of rat caecal content was found to be 70.73%依1.91% in 24 hours. Data of in-vitro release was fitted into Higuchi kinetics and Korsmeyer Peppas equation to explain release profile. The optimized formulation (FT4 showed zero order release. Conclusions: It is concluded that calcium alginate microbeads are the potential system for colon delivery of Tinidazole for chemotherapy of amoebic infection.

  7. Colonization of fish skin is vital for Vibrio anguillarum to cause disease.

    Science.gov (United States)

    Weber, Barbara; Chen, Chang; Milton, Debra L

    2010-02-01

    Vibrio anguillarum causes a fatal haemorrhagic septicaemia in marine fish. During initial stages of infection, host surfaces are colonized; however, few virulence factors required for colonization of the host are identified. In this study, in vivo bioluminescent imaging was used to analyse directly the colonization of the whole rainbow trout animal by V. anguillarum. The wild type rapidly colonized both the skin and the intestines by 24 h; however, the bacterial numbers on the skin were significantly higher than in the intestines indicating that skin colonization may be important for disease to occur. Mutants defective for the anguibactin iron uptake system, exopolysaccharide transport, or Hfq, an RNA chaperone, were attenuated for virulence, did not colonize the skin, and penetrated skin mucus less efficiently than the wild type. These mutants, however, did colonize the intestines and were as resistant to 2% bile salts as is the wild type. Moreover, exopolysaccharide mutants were significantly more sensitive to lysozyme and antimicrobial peptides, while the Hfq and anguibactin mutants were sensitive to lysozyme compared with the wild type. Vibrio anguillarum encodes several mechanisms to protect against antimicrobial components of skin mucus enabling an amazingly abundant growth on the skin enhancing its disease opportunities. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

  8. Automated polyp measurement based on colon structure decomposition for CT colonography

    Science.gov (United States)

    Wang, Huafeng; Li, Lihong C.; Han, Hao; Peng, Hao; Song, Bowen; Wei, Xinzhou; Liang, Zhengrong

    2014-03-01

    Accurate assessment of colorectal polyp size is of great significance for early diagnosis and management of colorectal cancers. Due to the complexity of colon structure, polyps with diverse geometric characteristics grow from different landform surfaces. In this paper, we present a new colon decomposition approach for polyp measurement. We first apply an efficient maximum a posteriori expectation-maximization (MAP-EM) partial volume segmentation algorithm to achieve an effective electronic cleansing on colon. The global colon structure is then decomposed into different kinds of morphological shapes, e.g. haustral folds or haustral wall. Meanwhile, the polyp location is identified by an automatic computer aided detection algorithm. By integrating the colon structure decomposition with the computer aided detection system, a patch volume of colon polyps is extracted. Thus, polyp size assessment can be achieved by finding abnormal protrusion on a relative uniform morphological surface from the decomposed colon landform. We evaluated our method via physical phantom and clinical datasets. Experiment results demonstrate the feasibility of our method in consistently quantifying the size of polyp volume and, therefore, facilitating characterizing for clinical management.

  9. Treatment of Oral Mucosal Lesions Associated With Overlapping Psychodermatologic Disorders.

    Science.gov (United States)

    Alfaris, Sausan; France, Katherine; Sollecito, Thomas P; Stoopler, Eric T

    2018-04-01

    Delusional infestations are psychodermatologic disorders in which those affected have a false belief they are infested by parasites and/or "growing" inanimate objects from cutaneous surfaces. Individuals with delusional parasitosis (DP) believe parasites, bacteria, worms, mites, or other living organisms are the source of cutaneous symptoms, while those with Morgellons disease (MD) attribute their symptoms to growth of small fibers or inorganic material. In both DP and MD, self-inflicted, non-healing cutaneous lesions caused by scratching at the affected areas to alleviate symptoms are commonly observed. This report describes a case of oral mucosal lesions in a patient demonstrating overlapping symptoms of DP and MD. It is important for oral healthcare providers to recognize oral signs and symptoms that may be associated with psychodermatologic disorders.

  10. Immunity and Tolerance Induced by Intestinal Mucosal Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Julio Aliberti

    2016-01-01

    Full Text Available Dendritic cells present in the digestive tract are constantly exposed to environmental antigens, commensal flora, and invading pathogens. Under steady-state conditions, these cells have high tolerogenic potential, triggering differentiation of regulatory T cells to protect the host from unwanted proinflammatory immune responses to innocuous antigens or commensals. On the other hand, these cells must discriminate between commensal flora and invading pathogens and mount powerful immune response against pathogens. A potential result of unbalanced tolerogenic versus proinflammatory responses mediated by dendritic cells is associated with chronic inflammatory conditions, such as Crohn’s disease, ulcerative colitis, food allergies, and celiac disease. Herein, we review the dendritic cell population involved in mediating tolerance and immunity in mucosal surfaces, the progress in unveiling their development in vivo, and factors that can influence their functions.

  11. Effects of Mycotoxins on Mucosal Microbial Infection and Related Pathogenesis

    Science.gov (United States)

    Park, Seong-Hwan; Kim, Dongwook; Kim, Juil; Moon, Yuseok

    2015-01-01

    Mycotoxins are fungal secondary metabolites detected in many agricultural commodities and water-damaged indoor environments. Susceptibility to mucosal infectious diseases is closely associated with immune dysfunction caused by mycotoxin exposure in humans and other animals. Many mycotoxins suppress immune function by decreasing the proliferation of activated lymphocytes, impairing phagocytic function of macrophages, and suppressing cytokine production, but some induce hypersensitive responses in different dose regimes. The present review describes various mycotoxin responses to infectious pathogens that trigger mucosa-associated diseases in the gastrointestinal and respiratory tracts of humans and other animals. In particular, it focuses on the effects of mycotoxin exposure on invasion, pathogen clearance, the production of cytokines and immunoglobulins, and the prognostic implications of interactions between infectious pathogens and mycotoxin exposure. PMID:26529017

  12. Histopathology of cutaneous and mucosal lesions in human paracoccidioidomycosis

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    Fabio Uribe

    1987-04-01

    Full Text Available Biopsies from cutaneous and mucosal lesions from 40 patients with active paracoccidioidomycosis, were studied histopathologically. All cases exhibited chronic granulomatous inflammation and 38 also presented suppuration; this picture corresponded to the mixed mycotic granuloma (MMG. Pseudoepitheliomatous hyperplasia and the transepidermic (or epithelial elimination of the parasite, were observed in all cases. In paracoccidioidomycosis elimination takes place through formation of progressive edema, accompained by exocytosis. The edema gives rise to spongiosis, microvesicles and microabscesses which not only contain the fungus but also, various cellular elements. Cells in charge of the phagocytic process were essentialy Langhans giant cells; PMN's, epithelioid and foreign body giant cells were poor phagocytes. An additional finding was the presence of fibrosis in most biopsies.

  13. [Cutaneous and mucosal manifestations associated with cocaine use].

    Science.gov (United States)

    Imbernón-Moya, Adrián; Chico, Ricardo; Aguilar-Martínez, Antonio

    2016-06-17

    Complications due to cocaine are a public health problem. The typical cutaneous disease is leukocytoclastic vasculitis and/or thrombotic vasculopathy affecting mainly the ears. No intense systemic involvement is usually present, but there may be several cutaneous, mucosal and systemic manifestations. Other findings associated as arthralgia, neutropaenia or agranulocytosis, low titer positive antinuclear antibodies, antiphospholipid antibody positivity and neutrophil cytoplasmic antibodies against multiple antigens help the diagnosis. This disease requires a clinical suspicion with a clinical history, a complete physical examination and a broad differential diagnosis for an early and correct diagnosis. The course is usually self-limited. In most cases the only treatment is to discontinue the use of cocaine associated with symptomatic treatment, no proven benefit of systemic corticosteroids. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  14. Cell proliferation and ageing in mouse colon

    International Nuclear Information System (INIS)

    Hamilton, E.; Franks, L.M.

    1980-01-01

    Cell kinetic parameters in the descending colon of unirradiated mice, 3-30-months-old were compared with those in mice irradiated repeatedly from the age of 6 or 24 months. The latter animals were given 1250 rad local X-irradiation to the colon every 6 weeks. Dose-survival curves showed the colon crypts of 6 and 24-months-old mice were similarly radiosensitive. In unirradiated mice the number of crypts per colon section decreased significantly at 30 months, but no significant age-related changes were seen in crypt size or labelling index (LI). Cell proliferation returned to control levels within 6 weeks of each X-ray dose and remained at this level for 20 weeks after the final dose. Later, cell proliferation in the irradiated colon fell significantly below control. A total of 6 or 7 doses each of 1250 rad produced only 1 colon carcinoma amongst 50 mice kept until they died. (author)

  15. Historical and Current Trends in Colon Trauma

    Science.gov (United States)

    Causey, Marlin Wayne; Rivadeneira, David E.; Steele, Scott R.

    2012-01-01

    The authors discuss the evolution of the evaluation and management of colonic trauma, as well as the debate regarding primary repair versus fecal diversion. Their evidence-based review covers diagnosis, management, surgical approaches, and perioperative care of patients with colon-related trauma. The management of traumatic colon injuries has evolved significantly over the past 50 years; here the authors describe a practical approach to the treatment and management of traumatic injuries to the colon based on the most current research. However, management of traumatic colon injuries remains a challenge and continues to be associated with significant morbidity. Familiarity with the different methods to the approach and management of colonic injuries will allow surgeons to minimize unnecessary complications and mortality. PMID:24294119

  16. Complications of acromegaly: thyroid and colon.

    Science.gov (United States)

    Tirosh, Amit; Shimon, Ilan

    2017-02-01

    In acromegaly the long-term exposure to high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels may result in specific complications in different human organs, including the thyroid gland and the colon. We will review here the evidence available regarding the characteristic thyroid and colon complications in acromegaly. This review summarizes the published data observing noncancerous structural abnormalities (thyroid nodules, colonic polyps) and thyroid and colon cancer in patients diagnosed with acromegaly. Thyroid micro-carcinomas are probably over-diagnosed among acromegalic patients. In regard to colon cancer, there is no sufficient data to suggest that colon cancer risk is higher in acromegaly compared to the general population.

  17. Image diagnostic of colonic diseases - controversial questions

    International Nuclear Information System (INIS)

    Pomakov, P.; Rizov, A.; Stancheva, I.

    2013-01-01

    In the system of colonic diseases' diagnostic algorithm, fibrocolonoscopy (FCS) is defined as 'Golden Standard'. By this reason some X-ray diagnostic methods - irrigography, etc. are currently not being used in a number of health institutions. The aim of this study is a comparative analysis of FCS and irrigography diagnostic efficacy in various colonic diseases. For 10-years period, in cooperation with a gastroenterologist-gastroscopist, 2151 patients with various colonic diseases were evaluated by FCS and irrigography with pharmaco-diagnostics/when necessary. Advantage of FCS was established in diagnosing diseases with patho-morfologic changes on the inner surface of the colon - benign and malignant neoplastic processes, chronic inflammatory diseases, etc. At the same time functional changes - irritated colon syndrome, changes in defecation act, etc., are not an object of diagnosis through FCS. Correction in colonic diseases diagnostic algorithm is necessary. FCS should be mandatory. If result is negative - irrigography with pharmaco-diagnostics should be done. (authors)

  18. Removable denture-related oral mucosal lesions: descriptive clinical study

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    Gökçen Akçiçek

    2017-05-01

    Full Text Available Objective: The aim of this study was to investigate whether there was a relationship between removable denture-related oral mucosal lesions and denture type, and demographic characteristics. Materials and Method: The age, sex, denture type, systemic condition and medication use, presence of denture-related oral mucosal lesions (DROML, their locations and patients’ awareness of above mentioned lesions were recorded for 199 patients. Pearson chi-square test was used to analyse the relationship between the DROML and denture type, and demographic characteristics of the patients. Results: Among the patients included to the study, 122 (61.3% were female and 77 (38.7% were male. Ninety-six patients (48.2% exhibited DROML, whereas 103 patients (51.8% had no DROML. No relationship was detected between DROML and age, and sex (p>0.05. The most commonly detected DROML was denture stomatitis (34.7%. Denture stomatitis was significantly more frequently seen in partial denture wearers (p<0.05, while epulis fissuratum and flabby ridge were statistically more frequent in complete denture wearers (p<0.001. Traumatic ulcer was more frequently found in mandibular complete denture wearers (p<0.05, while epulis fissuratum and flabby ridge were significantly more common in maxillary complete denture wearers (p<0.001. Among the patients with DROML, 57.3% stated that they were unaware of these lesions. Conclusion: In this study sample, the rate of DROML was high in patients wearing removable dentures (48.2%, and more than half of the patients with DROML were not aware of these lesions. Upon these findings, it is considered that removable denture wearers should follow the denture usage instructions and should be informed about the importance of periodic controls.

  19. Effects of stimulated repopulation on oral mucositis during conventional radiotherapy

    International Nuclear Information System (INIS)

    Doerr, W.; Jacubek, A.; Kummermehr, J.; Herrmann, Th.; Doelling-Jochem, I.; Eckelt, U.

    1995-01-01

    The effect of local conditioning of human oral mucosa by silver nitrate solution (3%) on epithelial proliferation rates was tested in 11 healthy volunteers by in vitro labelling of biopsies with tritiated thymidine. Compared to control biopsies from 13 volunteers, stimulation over 3 days, 3 times per day, yielded a significant (p = 0.006) increase in the epithelial labelling index (LI) from 4.75 ± 0.32% to 6.85 ± 0.65%, i.e., by 44%. The increase in the absolute number of labelled cells per mm epithelial length was dependent on the overall cell density at the various intraoral sites and varied between 45% in the maxillary vestibule and 91% at the floor of the mouth. In an analysis of variance, stimulation turned out to be the most important source causing the effect (p = 0.011 for LI and 0.015 for labelled cells per mm). In a radiotherapy trial with conventional postoperative treatment with 5 x 2 Gy/week to a total dose of 60 Gy in 6 weeks, the left buccal mucosa in 10 patients with squamous cell carcinomas of the head and neck was conditioned (3% silver nitrate, 3 times per day, 5 days before and the first 2 days of radiotherapy) while the contralateral mucosa, receiving an identical dose, served as individual control. Mucositis scores according to the EORTC/RTOG or the Dische system showed that the time course and severity of the mucosal response was almost identical in both cheeks, which is in clear contrast to a previous clinical study (Maciejewski et al. Radiother. Oncol. 22, 7-11, 1991). Differences in radiation dose intensity, i.e., weekly dose, in these studies are discussed as a tentative explanation for the different clinical findings

  20. Comparison of Alloderm and mucosal graft in mandibular vestibuloplasty

    Directory of Open Access Journals (Sweden)

    Mahmoodhashemi H.

    2009-12-01

    Full Text Available "nBackground and Aim: The usage of free gingival grafts for vestibuloplasty is a routine procedure. The free gingival procedure requires harvesting the graft from a donor site which increases morbidity and the risk of surgical complications. In addition, adequate amount of donor tissue may not be available. Acceptable results of Alloderm application as a substitute for autogenous soft tissue grafts are: Not exposing the patient to an additional surgery, no donor site morbidity, unlimited availability, decreasing the bleeding during the surgery, decreasing the surgical complications, and better color match. The aim of this study was to evaluate the maintenance of the vestibular depth in vestibuloplasty with mucosal graft and Alloderm."nMaterials and Methods: Both methods of anterior mandibular vestibuloplasty by Clark, utilizing Alloderm and mucosal grafts, were employed in ten clinical cases. During the surgeries, half the prepared recipient sites received Alloderm, while the remaining half received autografts in a randomized fashion. Immediately, 1, 3, and 6 months postoperatively, the variables of graft rejection, depth of vestibule and the degree of relapse were evaluated. SPSS software was used for analysis of the data and the methods used for "statistical tests" were as follows: Friedman Method, Paired sample t-test, Smirnov-kolmogrove Method. (The statistical significance level was established at P-value<0.05."nResults: The mean difference of the relapse measurements in both methods throughout the survey did not have significant predictive value (P>0.05. Similar results were achieved for the mean difference of depth of the vestibule."nConclusion: In patients undergoing Vestibuloplasty, Alloderm could be material of choice to be utilized as autogenic soft tissue grafts in pre-prosthesis procedures.

  1. Evaluation of mast cells, eosinophils, blood capillaries in oral lichen planus and oral lichenoid mucositis.

    Science.gov (United States)

    Reddy, D Santhosh; Sivapathasundharam, B; Saraswathi, T R; SriRam, G

    2012-01-01

    Mast cells are granule containing secretory cells present in oral mucosal and connective tissue environment. Oral lichen planus and oral lichenoid lesions are commonly occurring oral diseases and have some similarity clinically and histologically. Both are characterized by an extensive sub epithelial infiltrate of T cells, together with mast cells, eosinophils and blood capillaries. In this study mast cell and eosinophil densities along with number of blood capillaries were studied to find out if they could aid in histopathological distinction between oral lichen planus and lichenoid mucositis. To enumerate mast cells and compare the status of Mast Cells (Intact or Degranulated) in Lichen planus, Lichenoid mucositis and normal buccal mucosa in tissue sections stained with Toluidine Blue, and also to enumerate Eosinophils and blood capillaries in tissue sections stained with H and E. The study group included 30 cases each of oral lichen planus and oral lichenoid mucositis. 10 cases of clinically normal oral buccal mucosa formed the control group. All the sections were stained with Toluidine blue and H and E separately. Histopathological analysis was done using binocular light microscope equipped with square ocular grid to standardize the field of evaluation. The result of the study showed. · Significant increase in number of mast cells in oral lichen planus and oral lichenoid mucositis compared to normal buccal mucosa. · Significant increase of intact mast cells suepithelially within the inflammatory cell infiltrate in oral lichen planus compared to oral lichenoid mucositis. · Significant increase of degranulated mast cells in oral lichenoid mucositis to oral lichen planus, and increase in number of eosinophil densities in oral lichenoid mucositis compared to oral lichen planus. · Significant increase in number of capillaries in oral lichenoid mucositis compared to oral lichen planus. The findings of increased number of intact mast cells sub epithelially in oral

  2. Historical and Current Trends in Colon Trauma

    OpenAIRE

    Causey, Marlin Wayne; Rivadeneira, David E.; Steele, Scott R.

    2012-01-01

    The authors discuss the evolution of the evaluation and management of colonic trauma, as well as the debate regarding primary repair versus fecal diversion. Their evidence-based review covers diagnosis, management, surgical approaches, and perioperative care of patients with colon-related trauma. The management of traumatic colon injuries has evolved significantly over the past 50 years; here the authors describe a practical approach to the treatment and management of traumatic injuries to th...

  3. Perforated Solitary Diverticulitis of the Ascending Colon

    Science.gov (United States)

    2005-06-01

    postoperative day 6. DISCUSSION Diverticuli of the right colon exist in approximately 1% to 5% of patients with diverticular disease .1-3 They are...ORIGINAL REPORTS Perforated Solitary Diverticulitis of the Ascending Colon CPT David S. Kauvar, MC, USA, MAJ, Jayson Aydelotte, MC, USA, and MAJ...Michael Harnisch, MC, USA Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas KEY WORDS: solitary colon diverticulum

  4. Volvulus of the Small Bowel and Colon

    Science.gov (United States)

    Kapadia, Muneera R.

    2017-01-01

    Volvulus of the intestines may involve either the small bowel or colon. In the pediatric population, small bowel volvulus is more common, while in the adult population, colonic volvulus is more often seen. The two most common types of colonic volvulus include sigmoid and cecal volvulus. Prompt diagnosis and treatment is imperative, otherwise bowel ischemia may ensue. Treatment often involves emergent surgical exploration and bowel resection. PMID:28144211

  5. Dome-type carcinoma of the colon; a rare variant of adenocarcinoma resembling a submucosal tumor: a case report

    Directory of Open Access Journals (Sweden)

    Yamada Masayoshi

    2012-03-01

    Full Text Available Abstract Background Dome-type carcinoma (DC is a distinct variant of colorectal adenocarcinoma and less than 10 cases have been described in the literature. Most of the previously reported cases were early lesions and no endoscopic observations have been described so far. We herein report a case of a DC invading the subserosal layer, including endoscopic findings. Case presentation A highly elevated lesion in the transverse colon was diagnosed by colonoscopy in a 77-year-old man. The tumor appeared to be similar to a submucosal tumor (SMT, however, a demarcated area of reddish and irregular mucosa was observed at the top of the tumor. There were no erosions or ulcers. Laparoscopic-assisted right hemicolectomy was performed and pathological examination revealed a well-circumscribed tumor invading the subserosal layer. The tumor was a well-differentiated adenocarcinoma associated with a dense lymphocytic infiltration and showed expansive growth. The overlying mucosal layer showed high-grade dysplasia. Conclusion The present lesion was diagnosed as a DC of the colon invading the subserosal layer. Because the association of mucosal dysplasia is common in DCs, the detection of dysplastic epithelium would be important to discriminate DCs from SMTs.

  6. Efecto citotóxico en colon humano de Escherichia coli enterohemorrágico aislado de terneros con diarrea sanguinolenta Cytotoxic effect in human colon of enterohemorrhagic Escherichia coli isolated from calves with bloody diarrhea

    Directory of Open Access Journals (Sweden)

    V. Pistone Creydt

    2005-09-01

    Full Text Available Escherichia coli productor de toxina Shiga (STEC es el patógeno emergente en alimentos de mayor impacto, siendo su principal reservorio el ganado bovino. STEC puede causar diarrea, colitis hemorrágica y síndrome urémico hemolítico. El presente trabajo estudió la acción citotóxica de dos cepas de STEC aisladas de heces de terneros diarreicos en colon humano in vitro. Los fragmentos se montaron como un diafragma en una cámara de Ussing y se incubaron con las cepas patógenas. El flujo neto absortivo de agua (Jw disminuyó y la corriente de cortocircuito (Isc aumentó significativamente (P Shiga toxin-producing E. coli (STEC is one of the most important emergent pathogen in foods, being its main reservoir bovine cattle. STEC can cause diarrhea, hemorrhagic colitis and hemolytic-uremic syndrome. The present work have studied the cytotoxic action in human colon of cultures of two STEC strains isolated from faeces of calves with bloody diarrhea. Colonic mucosa was mounted as a diaphragm in a Ussing chamber and incubated with the cultures of pathogenic strains. Net water flow (Jw decreased and the short-circuit current (Isc increased significantly (p < 0,01 compared to negative control. Tissues showed an erosion of the mucose, epithelial exfoliation, and presence of pseudo-membranes in the lumen. Mild circulatory lesions were observed in the lamina propia. A moderate neutrophils infiltration was observed in the lumen and into the epithelial cells. Colonic crypts were not disrupted. Both experimental strains caused a similar lesion on colon tissues. This is the first study that shows that cultures of STEC strains isolated from bovine cattle produce cytotoxic effects in vitro in human colon.

  7. Polystyrene nanoparticles facilitate the internalization of impermeable biomolecules in non-tumour and tumour cells from colon epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Cabeza, Laura [University of Granada, Department of Human Anatomy and Embryology, Institute of Biopathology and Regenerative Medicine (IBIMER) (Spain); Cano-Cortés, Victoria; Rodríguez, María J. [University of Granada, Department of Pharmaceutical and Organic Chemistry (Spain); Vélez, Celia; Melguizo, Consolación, E-mail: melguizo@ugr.es [University of Granada, Department of Human Anatomy and Embryology, Institute of Biopathology and Regenerative Medicine (IBIMER) (Spain); Sánchez-Martín, Rosario M., E-mail: rmsanchez@ugr.es [University of Granada, Department of Pharmaceutical and Organic Chemistry (Spain); Prados, Jose [University of Granada, Department of Human Anatomy and Embryology, Institute of Biopathology and Regenerative Medicine (IBIMER) (Spain)

    2015-01-15

    Advanced colon cancer has a poor prognosis due to the limited effectiveness of current chemotherapies. Treatment failures may be avoided by the utilization of nanoparticles, which can enhance the effects of antitumor drugs, reduce their side effects and increase their directionality. Polystyrene nanoparticles have shown high biocompatibility and appropriate physicochemical properties and may represent a novel and more effective approach against colon cancer. In the present study, polystyrene nanoparticles were synthesized and fluorescently labelled, analyzing their cell internalization, intracellular localization and capacity to release transported molecules in tumour and non-tumour human colon cell lines (T84 and CCD-18). Flow cytometry and fluorescence microscopy studies demonstrated that polystyrene nanoparticles are an effective vehicle for the intracellular delivery of small molecules into colon epithelium cells. The percentage cell uptake was around 100 % in both T84 and CCD-18 cell lines after only 24 h of exposure and was cell confluence-independent. The polystyrene nanoparticles showed no cytotoxicity in either colon cell line. It was found that small molecules can be efficiently delivered into colon cells by using a disulphide bridge as release strategy. Analysis of the influence of the functionalization of the polystyrene nanoparticles surface on the internalization efficiency revealed some morphological changes in these cells. These results demonstrate that polystyrene nanoparticles may improve the transport of biomolecules into colon cells which could have a potential application in chemotherapeutic treatment against colon cancer.

  8. Polystyrene nanoparticles facilitate the internalization of impermeable biomolecules in non-tumour and tumour cells from colon epithelium

    International Nuclear Information System (INIS)

    Cabeza, Laura; Cano-Cortés, Victoria; Rodríguez, María J.; Vélez, Celia; Melguizo, Consolación; Sánchez-Martín, Rosario M.; Prados, Jose

    2015-01-01

    Advanced colon cancer has a poor prognosis due to the limited effectiveness of current chemotherapies. Treatment failures may be avoided by the utilization of nanoparticles, which can enhance the effects of antitumor drugs, reduce their side effects and increase their directionality. Polystyrene nanoparticles have shown high biocompatibility and appropriate physicochemical properties and may represent a novel and more effective approach against colon cancer. In the present study, polystyrene nanoparticles were synthesized and fluorescently labelled, analyzing their cell internalization, intracellular localization and capacity to release transported molecules in tumour and non-tumour human colon cell lines (T84 and CCD-18). Flow cytometry and fluorescence microscopy studies demonstrated that polystyrene nanoparticles are an effective vehicle for the intracellular delivery of small molecules into colon epithelium cells. The percentage cell uptake was around 100 % in both T84 and CCD-18 cell lines after only 24 h of exposure and was cell confluence-independent. The polystyrene nanoparticles showed no cytotoxicity in either colon cell line. It was found that small molecules can be efficiently delivered into colon cells by using a disulphide bridge as release strategy. Analysis of the influence of the functionalization of the polystyrene nanoparticles surface on the internalization efficiency revealed some morphological changes in these cells. These results demonstrate that polystyrene nanoparticles may improve the transport of biomolecules into colon cells which could have a potential application in chemotherapeutic treatment against colon cancer

  9. Oral delivery of prolyl hydroxylase inhibitor: AKB-4924 promotes localized mucosal healing in a mouse model of colitis.

    Science.gov (United States)

    Marks, Ellen; Goggins, Bridie J; Cardona, Jocelle; Cole, Siobhan; Minahan, Kyra; Mateer, Sean; Walker, Marjorie M; Shalwitz, Robert; Keely, Simon

    2015-02-01

    Pharmacological induction of hypoxia-inducible factor (HIF), a global transcriptional regulator of the hypoxic response, by prolyl hydroxylase inhibitors (PHDi) is protective in murine models of colitis, and epithelial cells are critical for the observed therapeutic efficacy. Because systemic HIF activation may lead to potentially negative off-target effects, we hypothesized that targeting epithelial HIF through oral delivery of PHDi would be sufficient to protect against colitis in a mouse model. Using a chemically induced trinitrobenzene sulfonic acid murine model of colitis, we compared the efficacy of oral and intraperitoneal (i.p.) delivery of the PHDi; AKB-4924 in preventing colitis, as measured by endoscopy, histology, barrier integrity, and immune profiling. Furthermore, we measured potential off-target effects, examining HIF and HIF target genes in the heart and kidney, as well as erythropoietin and hematocrit levels. Oral administration of AKB-4924 exhibited mucosal protection comparable i.p. dosing. Oral delivery of PHDi led to reduced colonic epithelial HIF stabilization compared with i.p. delivery, but this was still sufficient to induce transcription of downstream HIF targets. Furthermore, oral delivery of PHDi led to reduced stabilization of HIF and activation of HIF targets in extraintestinal organs. Oral delivery of PHDi therapies to this intestinal mucosa protects against colitis in animal models and represents a potential therapeutic strategy for inflammatory bowel disease, which also precludes unwanted extraintestinal effects.

  10. Sigmoid colon vaginoplasty in children.

    Science.gov (United States)

    Ekinci, S; Karnak, I; Ciftci, A O; Senocak, M E; Tanyel, F C; Büyükpamukçu, N

    2006-06-01

    Vaginal construction is necessary for the patients with aplasia of Mullerian ducts, testicular feminisation and androgen insensitivity syndromes. Many methods of vaginal construction have been described. We report here the outcomes of six adolescent patients who underwent sigmoid colon vaginoplasty with special emphasis on the surgical technique and outcomes. Between 1990 and 2003, six patients underwent sigmoid vaginoplasty after a diagnosis of 5alpha-reductase deficiency (n = 3), testicular feminisation (n = 2) or vaginal atresia (n = 1). The mean age was 16 years (13 to 18). Wide spectrum antibiotics and whole-gut preparation were used in all cases. A 15-20 cm segment of sigmoid colon was pulled through the retrovesical tunnel. The proximal end was closed in two layers in patients with 5alpha-reductase deficiency and with testicular feminisation. A distal anastomosis was carried out to the opening made on the vaginal plate (5alpha-reductase deficiency) or on the tip of the shallow rudimentary vagina (testicular feminisation). The sigmoid segment was interposed between the blind end of the atretic vagina and the perineum in the patient with vaginal atresia. Patients were instructed to perform daily vaginal irrigation. The neovagina was examined and calibrated under anaesthesia. No routine vaginal dilatation was recommended. All but one patient had an uneventful postoperative period and were discharged within 7-8 days. All patients had an excellent cosmetic result with an appropriate vaginal length. One of the patients experienced late stenosis of the introitus which responded to dilatations. Mucus discharge was not a significant problem. The patient with vaginal atresia (Bardet-Biedl syndrome) experienced deep vein thrombosis, renal failure and sepsis, resulting in death. Sigmoid colon vaginoplasty is a special procedure which appears appropriate for the construction of a new vagina in children. A sigmoid colon neovagina meets all necessary criteria after a

  11. Colonic diseases: The value of US examination

    International Nuclear Information System (INIS)

    Hollerweger, Alois

    2007-01-01

    The colon is affected by a number of diseases, mainly inflammatory, ischemic, and neoplastic conditions. Depending upon clinical indications endoscopy, US, CT, or other radiological methods are used for evaluation. The fact that US is frequently used as the initial imaging method in patients with non-specific clinical symptoms allows for greater influence in further diagnostic evaluation and with treatment, provided the investigator is familiar with the features of different intestinal diseases. This article will describe the anatomical characteristics of the colon, the US technique for examination of the colon, and the typical US features of the more common diagnoses of the colon

  12. Muscarinic Receptor Signaling in Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rosenvinge, Erik C. von, E-mail: evonrose@medicine.umaryland.edu; Raufman, Jean-Pierre [University of Maryland School of Medicine, Division of Gastroenterology & Hepatology, 22 S. Greene Street, N3W62, Baltimore, MD 21201 (United States); Department of Veterans Affairs, VA Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201 (United States)

    2011-03-02

    According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

  13. Muscarinic Receptor Signaling in Colon Cancer

    International Nuclear Information System (INIS)

    Rosenvinge, Erik C. von; Raufman, Jean-Pierre

    2011-01-01

    According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer

  14. Muscarinic Receptor Signaling in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Raufman

    2011-03-01

    Full Text Available According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

  15. Antibody production by the pig colon during infection with Treponema hyodysenteriae.

    Science.gov (United States)

    Rees, A S; Lysons, R J; Stokes, C R; Bourne, F J

    1989-09-01

    When 47 pigs were dosed orally with cultures of Treponema hyodysenteriae, 44 (94 per cent) developed swine dysentery. Of those which recovered and were rechallenged, nine of 21 (43 per cent) showed clinical signs, as did one of 10 (10 per cent) challenged on a third occasion. Clinical disease was associated with development of specific IgG, IgA and IgM antibodies in serum and the local production of IgA in gut mucosal tissues. The appearance of antibody was not directly related to protection but rather indicated either prolonged exposure (in the case of serum IgG) or recent exposure to T hyodysenteriae (for secretory IgA). Infection also resulted in the appearance of IgG and IgA memory cells in gut-associated lymphoid tissue. However, these studies indicated that humoral immunity alone is not responsible for the onset of a protective response to T hyodysenteriae in the colon.

  16. IBS, NERD and functional dyspepsia are immuno-neuronal disorders of mucosal cytokine imbalances clinically reversible with high potency sucralfate.

    Science.gov (United States)

    McCullough, Ricky W

    2013-03-01

    Irritable bowel syndrome (IBS), non-erosive reflux disorder (NERD), and functional dyspepsia (FD) are best classified as immuno-neuronal disorders of the mucosa or functional mucosal syndromes (FMS). Each appears to be clinically reversible using high potency sucralfate (HPS). In FMS of the GI tract, postprandial nausea, altered motility, discordant peristalsis, vomiting, diarrhea, and hyperalgesia are the clinical expressions of a mucosal imbalance between pro-inflammatory cytokines of up-regulated intra-epithelial lymphocytes (IELs) and feedback anti-inflammatory cytokines tasked with moderating the antigenic response of IELs. Normal functioning GI tract requires an operative balance between pro-inflammatory and anti-inflammatrory cytokines, a balance governed by locally expressed growth factors. The surface concentration of sucralfate can be enhanced 7-23-fold by suspending it in a select concentration of cations and multi-dentate cationic chelators. Increased surface concentration of sucralfate facilitates novel dose effects which include efficient activation of growth factors, quiescence of gated-nociceptor firing and resultant restoration of normal GI function. Published by Elsevier Ltd.

  17. Biofilm formation is determinant in tomato rhizosphere colonization by Bacillus velezensis FZB42.

    Science.gov (United States)

    Al-Ali, Ameen; Deravel, Jovana; Krier, François; Béchet, Max; Ongena, Marc; Jacques, Philippe

    2017-10-23

    In this work, the behavior in tomato rhizosphere of Bacillus velezensis FZB42 was analyzed taking into account the surfactin production, the use of tomato roots exudate as substrates, and the biofilm formation. B. velezensis FZB42 and B. amyloliquefaciens S499 have a similar capability to colonize tomato rhizosphere. Little difference in this colonization was observed with surfactin non producing B. velezensis FZB42 mutant strains. B. velezensis is able to grow in the presence of root exudate and used preferentially sucrose, maltose, glutamic, and malic acids as carbon sources. A mutant enable to produce exopolysaccharide (EPS - ) was constructed to demonstrate the main importance of biofilm formation on rhizosphere colonization. This mutant had completely lost its ability to form biofilm whatever the substrate present in the culture medium and was unable to efficiently colonize tomato rhizosphere.

  18. A Colon Targeted Delivery System for Resveratrol Enriching in pH Responsive-Model

    DEFF Research Database (Denmark)

    Andishmand, Hashem; Hamishehkar, Hamed; Mohammadifar, Mohammad Amin

    2017-01-01

    Background: Resveratrol effects on the prevention and treatment of colon cancer have been well documented recently, but low solubility, rapid absorption and metabolism of resveratrol limit its beneficial effects on colon cancer. Designing a formulation that enhances the solubility of resveratrol......, protects resveratrol from oxidation and isomerization, and delivers it to the colon is a priority of food and drug industry. In this study, resveratrol-polyethylene glycol (PEG)-loaded pectin-chitosan polyelectrolyte complex was designed as a colon targeted delivery system. Methods: The effects of adding...... PEG, ultra-sonication time, pH, and pectin to chitosan ratio were investigated on particle size, polydispersity index (PDI), zeta potential by particle size analyzer, and scanning electron microscopy (SEM). Encapsulation efficiency (EE), release of resveratrol in simulated gastrointestinal fluid...

  19. Beneficial Effects of Anti-Interleukin-6 Antibodies on Impaired Gastrointestinal Motility, Inflammation and Increased Colonic Permeability in a Murine Model of Sepsis Are Most Pronounced When Administered in a Preventive Setup.

    Directory of Open Access Journals (Sweden)

    Sara Nullens

    Full Text Available During sepsis, gastrointestinal ileus, mucosal barrier dysfunction and bacterial translocation are accepted to be important triggers that can maintain or exacerbate the septic state. In the caecal ligation and puncture animal model of sepsis, we demonstrated that systemic and colonic interleukin-6 levels are significantly increased coinciding with an impaired colonic barrier function. We therefore aimed to study the effect of therapeutic or curative administration of anti-IL6 antibodies on overall GI motility, colonic permeability and translocation of intestinal bacteria in blood and mesenteric lymph nodes in the mouse caecal ligation and puncture model.OF-1 mice were randomized to either the preventive or curative protocol, in which they received 1 mg/kg of antibodies to interleukin-6, or its IgG isotype control solution. They subsequently underwent either the caecal ligation and puncture procedure, or sham-surgery. GI motility was assessed 48 h following the procedure, as well as colonic permeability, serum and colon cytokines, colonic tight junction proteins at the mRNA level; cultures of blood and mesenteric lymph nodes were performed.Preventive administration of anti-interleukin-6 antibodies successfully counteracted the gastrointestinal motility disturbances and impaired colonic barrier function that could be observed in vehicle-treated septic animals. Serum and colonic levels of proinflammatory cytokines were significantly lower when animals were preventively treated with anti-interleukin-6 antibodies. A repetitive injection 24 h later resulted in the most pronounced effects. Curative treatment significantly lowered systemic and colonic inflammation markers while the effects on transit and permeability were unfortunately no longer significant.Caecal ligation and puncture resulted in septic ileus with an increased colonic permeability. Antibodies to interleukin-6 were able to ameliorate gastro-intestinal motility, suppress inflammation and

  20. Experimental study of virtual colonoscopy of simulated mass lesions in pig colon: comparison of CT and MR techniques

    International Nuclear Information System (INIS)

    Yang Xiujun; He Zhiyan; Tao Yonghao; Miao Jingtao; Chen Yuanjiong; Hu Yuansheng; Wang Linchuan

    2000-01-01

    Objective: To probe into the technique and diagnostic value of MR vi