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Sample records for inflamed colonic mucosa

  1. Bax is downregulated in inflamed colonic mucosa of ulcerative colitis

    PubMed Central

    Iimura, M; Nakamura, T; Shinozaki, S; Iizuka, B; Inoue, Y; Suzuki, S; Hayashi, N

    2000-01-01

    BACKGROUND AND AIMS—One form of epithelial cell injury in inflamed colonic mucosa in ulcerative colitis (UC) is reported to involve apoptosis of these cells. Bcl-2 family proteins Bax and Bcl-2 are the major regulators of apoptosis. The aim of this study was to elucidate the involvement of the Bax/Bcl-2 system in induction of apoptosis of the inflamed colonic epithelium in UC.
METHODS—Colonic epithelium was isolated from colonic biopsy specimens. Expression of CD95, Bax, Bcl-xL, and Bcl-2 proteins was determined by western blotting. Bax gene expression was assessed by both reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern hybridisation and a real time PCR assay.
RESULTS—Equal levels of expression of CD95, Bcl-xL, and Bcl-2 proteins were noted in normal and UC colonic epithelia. Equal levels of expression of Bax protein and mRNA were noted in epithelia of normal colon and inactive UC. Levels of expression of Bax protein and mRNA were markedly reduced in inflamed UC colonic epithelium.
CONCLUSIONS—Our study showed for the first time downregulation of Bax in inflamed colonic epithelium of UC. The Bax/Bcl-2 system did not seem to be involved in induction of apoptosis of epithelial cells in the inflamed colonic mucosa of UC.


Keywords: ulcerative colitis; apoptosis; Bax; Bcl-2; Bcl-xL; CD95 PMID:10896914

  2. A novel protocol allowing oral delivery of a protein complement inhibitor that subsequently targets to inflamed colon mucosa and ameliorates murine colitis

    PubMed Central

    Elvington, M; Blichmann, P; Qiao, F; Scheiber, M; Wadsworth, C; Luzinov, I; Lucero, J; Vertegel, A; Tomlinson, S

    2014-01-01

    While there is evidence of a pathogenic role for complement in inflammatory bowel disease, there is also evidence for a protective role that relates to host defence and protection from endotoxaemia. There is thus concern regarding the use of systemic complement inhibition as a therapeutic strategy. Local delivery of a complement inhibitor to the colon by oral administration would ameliorate such concerns, but while formulations exist for oral delivery of low molecular weight drugs to the colon, they have not been used successfully for oral delivery of proteins. We describe a novel pellet formulation consisting of cross-linked dextran coated with an acrylic co-polymer that protects the complement inhibitor CR2-Crry from destruction in the gastrointestinal tract. CR2-Crry containing pellets administered by gavage, were characterized using a therapeutic protocol in a mouse model of dextran sulphate sodium (DSS)-induced colitis. Oral treatment of established colitis over a 5-day period significantly reduced mucosal inflammation and injury, with similar therapeutic benefit whether or not the proton pump inhibitor, omeprazole, was co-administered. Reduction in injury was associated with the targeting of CR2-Crry to the mucosal surface and reduced local complement activation. Treatment had no effect on systemic complement activity. This novel method for oral delivery of a targeted protein complement inhibitor will reduce systemic effects, thereby decreasing the risk of opportunistic infection, as well as lowering the required dose and treatment cost and improving patient compliance. Furthermore, the novel delivery system described here may provide similar benefits for administration of other protein-based drugs, such as anti-tumour necrosis factor-α antibodies. PMID:24730624

  3. Differences in cellular glycoconjugates of quiescent, inflamed, and neoplastic colonic epithelium in colitis and cancer-prone tamarins.

    PubMed Central

    Moore, R.; King, N.; Alroy, J.

    1988-01-01

    In the preceding paper the authors demonstrated that the lectin staining patterns of normal colonic epithelium obtained from colitis and carcinoma-prone cotton top tamarins (CTTs), Saguinus oedipus, a New World primate, differs from colitis- and carcinoma-resistant primate species. In this study they determined the usefulness of cytochemical features in inflamed epithelium as indicators for malignant change. They compared the lectin staining pattern in inflamed mucosa and adjacent mucosa with colonic carcinoma from 8 CTTs with that of 9 clinically healthy CTTs with no histologic evidence of colitis. Deparaffinized sections were labeled with ten biotinylated lectins and stained by the avidin-biotin peroxidase complex method. Numerous significant differences were demonstrated in the lectin staining pattern between normal epithelium and colonic carcinoma; fewer between normal and chronic inflamed epithelium. However, between chronic inflamed epithelium and colonic carcinoma significant staining differences were observed with only two lectins, peanut agglutinin (PNA) and Ulex europaeus agglutinin-I (UEA-I). These findings suggest that there is a progression in alteration of lectin staining pattern from normal epithelium, via chronic colitis, to colonic carcinoma. Furthermore, the differences between chronic colitis and colonic carcinoma are expressed only with those lectins that are associated with malignant transformation of human colonic epithelium. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3132858

  4. Differences in cellular glycoconjugates of quiescent, inflamed, and neoplastic colonic epithelium in colitis and cancer-prone tamarins.

    PubMed

    Moore, R; King, N; Alroy, J

    1988-06-01

    In the preceding paper the authors demonstrated that the lectin staining patterns of normal colonic epithelium obtained from colitis and carcinoma-prone cotton top tamarins (CTTs), Saguinus oedipus, a New World primate, differs from colitis- and carcinoma-resistant primate species. In this study they determined the usefulness of cytochemical features in inflamed epithelium as indicators for malignant change. They compared the lectin staining pattern in inflamed mucosa and adjacent mucosa with colonic carcinoma from 8 CTTs with that of 9 clinically healthy CTTs with no histologic evidence of colitis. Deparaffinized sections were labeled with ten biotinylated lectins and stained by the avidin-biotin peroxidase complex method. Numerous significant differences were demonstrated in the lectin staining pattern between normal epithelium and colonic carcinoma; fewer between normal and chronic inflamed epithelium. However, between chronic inflamed epithelium and colonic carcinoma significant staining differences were observed with only two lectins, peanut agglutinin (PNA) and Ulex europaeus agglutinin-I (UEA-I). These findings suggest that there is a progression in alteration of lectin staining pattern from normal epithelium, via chronic colitis, to colonic carcinoma. Furthermore, the differences between chronic colitis and colonic carcinoma are expressed only with those lectins that are associated with malignant transformation of human colonic epithelium. PMID:3132858

  5. Self assembled hyaluronic acid nanoparticles as a potential carrier for targeting the inflamed intestinal mucosa.

    PubMed

    Vafaei, Seyed Yaser; Esmaeili, Motahareh; Amini, Mohsen; Atyabi, Fatemeh; Ostad, Seyed Naser; Dinarvand, Rassoul

    2016-06-25

    To develop a nanoparticulate drug carrier for targeting of the inflamed intestinal mucosa, amphiphilic hyaluronic acid (HA) conjugates were synthesized, which could form self-assembled nanoparticles (NPs) in aqueous solution and budesonide (BDS) was loaded into the HANPs. Their particle sizes were in the range of 177 to 293nm with negative surface charge. The model of inflammatory CACO-2 cells was utilized to investigate the therapeutic potential of budesonide loaded HA nanocarriers. The highest expression of CD44 receptors was found on inflamed Caco-2 cells, as determined by flow cytometry. FITC-labeled HANPs revealed greater uptake in inflamed CACO-2 cells compared to untreated CACO-2 and CD44-negative cell lines, NIH3T3. BDS loaded HANPs displayed almost no toxicity indicating HANPs are excellent biocompatible nano-carriers. BDS loaded HANPs demonstrated higher anti-inflammatory effect on IL-8 and TNF-α secretion in inflamed cell model compared to the same dose of free drug. These results revealed the promising potential of HA nanoparticles as a targeted drug delivery system for IBD treatment. PMID:27083829

  6. Immunohistochemical changes in morphologically involved and uninvolved colonic mucosa of patients with idiopathic proctitis.

    PubMed Central

    Das, K M; Erber, W F; Rubinstein, A

    1977-01-01

    Alterations in secretory component, IgA, IgG, and IgM were studied by immunofluorescent techniques in mucosal biopsy specimens obtained at colonoscopy from inflamed and grossly uninvolved colonic mucosa from 12 patients with idiopathic proctitis. Parotid-salivary secretory component and IgA and serum immunoglobulins were also investigated. Decreased secretory IgA was observed in the epithelium of all grossly involved rectal mucosa and in 40% of proximal normal mucosa. Salivary secretory IgA was not diminished. These observations suggest that a local immune defect may be pathogenetically related to idiopathic proctitis. Images PMID:320226

  7. Detection of a fluorescent-labeled avidin-nucleic acid nanoassembly by confocal laser endomicroscopy in the microvasculature of chronically inflamed intestinal mucosa

    PubMed Central

    Buda, Andrea; Facchin, Sonia; Dassie, Elisa; Casarin, Elisabetta; Jepson, Mark A; Neumann, Helmut; Hatem, Giorgia; Realdon, Stefano; D’Incà, Renata; Sturniolo, Giacomo Carlo; Morpurgo, Margherita

    2015-01-01

    Inflammatory bowel diseases are chronic gastrointestinal pathologies causing great discomfort in both children and adults. The pathogenesis of inflammatory bowel diseases is not yet fully understood and their diagnosis and treatment are often challenging. Nanoparticle-based strategies have been tested in local drug delivery to the inflamed colon. Here, we have investigated the use of the novel avidin-nucleic acid nanoassembly (ANANAS) platform as a potential diagnostic carrier in an experimental model of inflammatory bowel diseases. Fluorescent- labeled ANANAS nanoparticles were administered to mice with chemically induced chronic inflammation of the large intestine. Localization of mucosal nanoparticles was assessed in vivo by dual-band confocal laser endomicroscopy. This technique enables characterization of the mucosal microvasculature and crypt architecture at subcellular resolution. Intravascular nanoparticle distribution was observed in the inflamed mucosa but not in healthy controls, demonstrating the utility of the combination of ANANAS and confocal laser endomicroscopy for highlighting intestinal inflammatory conditions. The specific localization of ANANAS in inflamed tissues supports the potential of this platform as a targeted carrier for bioactive moieties in the treatment of inflammatory bowel disease. PMID:25609952

  8. Colitis-induced neuroplasticity disrupts motility in the inflamed and post-inflamed colon

    PubMed Central

    Mawe, Gary M.

    2015-01-01

    Effective colonic motility involves an intricate pattern of excitatory and inhibitory neuromuscular signals that arise from the enteric neural circuitry of the colon. Recent investigations have demonstrated that inflammation leads to a variety of changes in the physiological properties of the neurons in this circuitry, including hyperexcitability of neurons at the afferent end of the peristaltic reflex, synaptic facilitation, and attenuated inhibitory neuromuscular transmission. Furthermore, links have been established between these changes and disrupted motor activity in the colon, and we now know that some of these changes persist long after recovery from inflammation. It is highly likely that inflammation-induced neuroplasticity, which is not detectable by clinical diagnostics, contributes to disrupted motility in active and quiescent inflammatory bowel disease and in functional gastrointestinal disorders. PMID:25729851

  9. Aberrant Gene Expression Profile of Unaffected Colon Mucosa from Patients with Unifocal Colon Polyp

    PubMed Central

    Lian, Jingjing; Ma, Lili; Yang, Jiayin; Xu, Lili

    2015-01-01

    Background The aim of this study was to evaluate gene expression profiles in unaffected colon mucosa and polyp tissue from patients with unifocal colon polyp to investigate the potential mucosa impairment in normal-appearing colon mucosa from these patients. Material/Methods Colon polyp patients were prospectively recruited. We obtained colon biopsies from the normal-appearing sites and polyp tissue through colonoscopy. Gene expression analysis was performed using microarrays. Gene ontology and clustering were evaluated by bioinformatics. Results We detected a total of 711 genes (274 up-regulated and 437 down-regulated) in polyp tissue and 256 genes (170 up-regulated and 86 down-regulated) in normal-appearing colon mucosa, with at least a 3-fold of change compared to healthy controls. Heatmapping of the gene expression showed similar gene alteration patterns between unaffected colon mucosa and polyp tissue. Gene ontology analyses confirmed the overlapped molecular functions and pathways of altered gene expression between unaffected colon mucosa and polyp tissue from patients with unifocal colon polyp. The most significantly altered genes in normal-appearing tissues in polyp patients include immune response, external side of plasma membrane, nucleus, and cellular response to zinc ion. Conclusions Significant gene expression alterations exist in unaffected colon mucosa from patients with unifocal colon polyp. Unaffected colon mucosa and polyp tissue share great similarity and overlapping of altered gene expression profiles, indicating the potential possibility of recurrence of colon polyps due to underlying molecular abnormalities of colon mucosa in these patients. PMID:26675397

  10. Epigenetic maturation in colonic mucosa continues beyond infancy in mice.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Monozygotic twin and other epidemiologic studies indicate that epigenetic processes may play an important role in the pathogenesis of inflammatory bowel diseases that commonly affect the colonic mucosa. The peak onset of these disorders in young adulthood, suggests that epigenetic changes normally o...

  11. Evaluation of Selected Cytokine Gene Expression in Colonic Mucosa from Dogs with Idiopathic Lymphocytic-plasmacytic Colitis

    PubMed Central

    TAMURA, Yu; OHTA, Hiroshi; YOKOYAMA, Nozomu; LIM, Sue Yee; OSUGA, Tatsuyuki; MORISHITA, Keitaro; NAKAMURA, Kensuke; YAMASAKI, Masahiro; TAKIGUCHI, Mitsuyoshi

    2014-01-01

    ABSTRACT Lymphocytic-plasmacytic colitis (LPC) is a common form of inflammatory bowel disease (IBD) affecting the canine large intestine. Cytokines are thought to be involved in the pathogenesis of IBD. However, to date, few studies have investigated cytokine mRNA expression in dogs with LPC. In this study, we investigated mRNA transcription levels of T helper cell cytokines, such as IFN-γ, IL-4, IL-17 and IL-10 and pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α, IL-8, IL-12 and IL-23, in colonic mucosa from LPC dogs by quantitative real-time RT-PCR. No significant differences were detected in cytokine mRNA expressions between dogs with LPC and controls, except for IL-23p19. Dogs with LPC failed to express a predominant cytokine profile in inflamed colonic mucosa as opposed to human IBD. PMID:24976586

  12. Alteration of gene expression in rat colon mucosa after exercise.

    PubMed

    Buehlmeyer, K; Doering, F; Daniel, H; Kindermann, B; Schulz, T; Michna, H

    2008-01-01

    The development of colon cancer is highly influenced by lifestyle factors such as nutrition and physical inactivity. Detailed biological mechanisms are thus far unclear. The purpose of this study was to investigate the effects of regular treadmill exercise on gene expression in rat colon mucosa. For this purpose, 6-week-old male Wistar rats completed a stress-free voluntary treadmill exercise period of 12 weeks. Sedentary rats served as a control group. In the colon mucosa, steady-state mRNA expression levels of approximately 10,000 genes were compared between both groups by micro-array analysis (MWG rat 10K array). A total of 8846 mRNAs were detected above background level. Regular exercise led to a decreased expression of 47 genes at a threshold-factor of 2.0. Three genes were found to be up-regulated in the exercise group. The identified genes encode proteins involved in signal transduction (n=11), transport (n=8), immune system (n=7), cytoskeleton (n=6), protein targeting (n=6), metabolism (n=5), transcription (n=3) and vascularization (n=2). Among the genes regulated by regular exercise, the betaine-homocysteine methyltransferase 2 (BHMT2) seems to be of particular interest. Physical activity may protect against aberrant methylation by repressing the BHMT2 gene and thus contribute to a decreased risk of developing colon cancer. We have also identified vascular endothelial growth factor (VEGF), angiopoietin-2 (ANG-2) and calcium-independent phospholipase a2 (iPL-A2), all of them with markedly reduced transcript levels in the mucosa of active rats. In summary, our experiment presents the first gene expression pattern in rat colon mucosa following regular treadmill activity and represents an important step in understanding the molecular mechanisms responsible for the preventive effect of physical activity on the development of colon cancer. PMID:18342145

  13. Proteome analysis of the macroscopically affected colonic mucosa of Crohn’s disease and intestinal tuberculosis

    PubMed Central

    Rukmangadachar, Lokesh A.; Makharia, Govind K.; Mishra, Asha; Das, Prasenjit; Hariprasad, Gururao; Srinivasan, Alagiri; Gupta, Siddhartha Datta; Ahuja, Vineet; Acharya, Subrat K.

    2016-01-01

    Differentiation between intestinal tuberculosis (ITB) and Crohn’s disease (CD) is challenging in geographical regions where both these diseases are prevalent. There is a need of biomarkers for differentiation between these two disorders. Colonic biopsies from inflamed mucosa of treatment-naive patients with ITB, CD and controls were used for analysis. Protein extracted from biopsies was digested with trypsin and resulting peptides were labeled with iTRAQ reagents. The peptides were subsequently analyzed using LC-MS/MS for identification and quantification. Gene ontology annotation for proteins was analyzed in PANTHER. Validation experiments were done for six differentially expressed proteins using immunohistochemistry. 533 proteins were identified and 241 proteins were quantified from 5 sets of iTRAQ experiments. While 63 were differentially expressed in colonic mucosa of patients with CD and ITB in at least one set of iTRAQ experiment, 11 proteins were differentially expressed in more than one set of experiments. Six proteins used for validation using immunohistochemistry in a larger cohort of patients; none of them however was differentially expressed in patients with ITB and CD. There are differentially expressed proteins in tissue proteome of CD and ITB. Further experiments are required using a larger cohort of homogeneous tissue samples. PMID:26988818

  14. Development, validation and implementation of an in vitro model for the study of metabolic and immune function in normal and inflamed human colonic epithelium.

    PubMed

    Pedersen, Gitte

    2015-01-01

    human colonic epithelial cells from endoscopic mucosal biopsies of patients with IBD. Short-time isolation by EGTA/EDTA from colonic biopsies allowed establishment of small scale cultures of epithelial cells which were viable and metabolic active for up to 48 hours in vitro. The cell model preserved important cellular metabolic and immunological functions of the human colonic epithelium, including the ability to oxidate butyrate, detoxificate phenolic compounds and secrete the chemokine interleukin (IL)-8 in vitro. Tumour necrosis factor (TNF)-α and interferon (IFN)-γ are pro-inflammatory cytokines, which are present in increased amounts in inflamed colonic mucosa. The precise mechanisms of cytokine-mediated mucosal injury are unknown, but one might be that TNF-α and IFN-γ directly impair epithelial cell function similar to effects seen on distinct target cells in other autoimmune diseases. Using the model, both cytokines were found directly to impair the viability of colonic epithelial cells and to induce secretion of IL-8 in vitro. Interestingly, the cells from inflamed IBD mucosa were less sensitive to cytokine-induced damage, which suggests that an intrinsic defense mechanism is triggered in these cells, perhaps as a result of exposure to toxic luminal factors or high local cytokine levels in vivo. TNF-α and IFN-γ may also be involved in regulation of intestinal inflammation through stimulation of MMP expression and proteolytic activity. We found that colonic epithelial cells express a range of MMPs and moreover that expression of distinct MMPs is increased in cells from inflamed IBD mucosa. Using a functional peptide cleavage assay it was shown that epithelial cells secreted proteolytic active enzymes and that the functional MMP activity was increased in inflamed IBD mucosa. This suggests that colonic epithelial cells, like myofibroblasts and immune cells, may contribute to local intestinal mucosal damage, through secretion of active MMPs. Disturbance of

  15. Adherence of Entamoeba histolytica trophozoites to rat and human colonic mucosa.

    PubMed Central

    Ravdin, J I; John, J E; Johnston, L I; Innes, D J; Guerrant, R L

    1985-01-01

    We studied the adherence of [3H]thymidine-labeled axenic Entamoeba histolytica (strain HM1-IMSS) to in vitro preparations of rat and human colonic mucosa. Studies were performed with fixed or unfixed rat colonic mucosa, unfixed rat mucosa exposed to trypsin, unfixed rat submucosa, and fixed human colonic mucosa. Twenty percent of the amebae adhered to fixed rat colonic mucosa; adherence was specifically inhibited by N-acetyl-D-galactosamine (GalNAc), galactose, and asialofetuin. The adherence of amebae to fixed human colonic mucosa was also GalNAc inhibitable. Greater adherence was found with unfixed rat colonic mucosa (40.9%) and was not GalNAc inhibitable unless the tissue was first exposed to trypsin. However, GalNAc did inhibit the adherence of amebae to unfixed rat submucosa. Glutaraldehyde fixation of amebae inactivates known amebic adhesion proteins; there was a markedly decreased adherence of fixed amebae to trypsin-exposed mucosa or fixed rat colonic mucosa. However, fixed or viable amebae had equal levels of adherence to unfixed rat colonic mucosa, suggesting the presence of a host adhesion protein that binds to receptors on amebae. Human (10%) and rabbit (5%) immune sera reduced the adherence of viable amebae to fixed rat colonic mucosa. We concluded that the GalNAc-inhibitable adhesion protein on the surface of E. histolytica trophozoites mediated adherence to fixed rat mucosa, fixed human colonic mucosa, trypsin-exposed unfixed rat mucosa, and unfixed rat submucosa. The surface of unfixed rat colonic mucosa contained a glutaraldehyde- and trypsin-sensitive host adhesion protein, perhaps in the overlying mucus blanket, which bound viable or fixed E. histolytica trophozoites. Images PMID:2580787

  16. Host lysozyme-mediated lysis of Lactococcus lactis facilitates delivery of colitis-attenuating superoxide dismutase to inflamed colons.

    PubMed

    Ballal, Sonia A; Veiga, Patrick; Fenn, Kathrin; Michaud, Monia; Kim, Jason H; Gallini, Carey Ann; Glickman, Jonathan N; Quéré, Gaëlle; Garault, Peggy; Béal, Chloé; Derrien, Muriel; Courtin, Pascal; Kulakauskas, Saulius; Chapot-Chartier, Marie-Pierre; van Hylckama Vlieg, Johan; Garrett, Wendy S

    2015-06-23

    Beneficial microbes that target molecules and pathways, such as oxidative stress, which can negatively affect both host and microbiota, may hold promise as an inflammatory bowel disease therapy. Prior work showed that a five-strain fermented milk product (FMP) improved colitis in T-bet(-/-) Rag2(-/-) mice. By varying the number of strains used in the FMP, we found that Lactococcus lactis I-1631 was sufficient to ameliorate colitis. Using comparative genomic analyses, we identified genes unique to L. lactis I-1631 involved in oxygen respiration. Respiration of oxygen results in reactive oxygen species (ROS) generation. Also, ROS are produced at high levels during intestinal inflammation and cause tissue damage. L. lactis I-1631 possesses genes encoding enzymes that detoxify ROS, such as superoxide dismutase (SodA). Thus, we hypothesized that lactococcal SodA played a role in attenuating colitis. Inactivation of the sodA gene abolished L. lactis I-1631's beneficial effect in the T-bet(-/-) Rag2(-/-) model. Similar effects were obtained in two additional colonic inflammation models, Il10(-/-) mice and dextran sulfate sodium-treated mice. Efforts to understand how a lipophobic superoxide anion (O2 (-)) can be detoxified by cytoplasmic lactoccocal SodA led to the finding that host antimicrobial-mediated lysis is a prerequisite for SodA release and SodA's extracytoplasmic O2 (-) scavenging. L. lactis I-1631 may represent a promising vehicle to deliver antioxidant, colitis-attenuating SodA to the inflamed intestinal mucosa, and host antimicrobials may play a critical role in mediating SodA's bioaccessibility. PMID:26056274

  17. Host lysozyme-mediated lysis of Lactococcus lactis facilitates delivery of colitis-attenuating superoxide dismutase to inflamed colons

    PubMed Central

    Ballal, Sonia A.; Veiga, Patrick; Fenn, Kathrin; Michaud, Monia; Kim, Jason H.; Gallini, Carey Ann; Glickman, Jonathan N.; Quéré, Gaëlle; Garault, Peggy; Béal, Chloé; Derrien, Muriel; Courtin, Pascal; Kulakauskas, Saulius; Chapot-Chartier, Marie-Pierre; van Hylckama Vlieg, Johan; Garrett, Wendy S.

    2015-01-01

    Beneficial microbes that target molecules and pathways, such as oxidative stress, which can negatively affect both host and microbiota, may hold promise as an inflammatory bowel disease therapy. Prior work showed that a five-strain fermented milk product (FMP) improved colitis in T-bet−/− Rag2−/− mice. By varying the number of strains used in the FMP, we found that Lactococcus lactis I-1631 was sufficient to ameliorate colitis. Using comparative genomic analyses, we identified genes unique to L. lactis I-1631 involved in oxygen respiration. Respiration of oxygen results in reactive oxygen species (ROS) generation. Also, ROS are produced at high levels during intestinal inflammation and cause tissue damage. L. lactis I-1631 possesses genes encoding enzymes that detoxify ROS, such as superoxide dismutase (SodA). Thus, we hypothesized that lactococcal SodA played a role in attenuating colitis. Inactivation of the sodA gene abolished L. lactis I-1631’s beneficial effect in the T-bet−/− Rag2−/− model. Similar effects were obtained in two additional colonic inflammation models, Il10−/− mice and dextran sulfate sodium-treated mice. Efforts to understand how a lipophobic superoxide anion (O2−) can be detoxified by cytoplasmic lactoccocal SodA led to the finding that host antimicrobial-mediated lysis is a prerequisite for SodA release and SodA’s extracytoplasmic O2− scavenging. L. lactis I-1631 may represent a promising vehicle to deliver antioxidant, colitis-attenuating SodA to the inflamed intestinal mucosa, and host antimicrobials may play a critical role in mediating SodA’s bioaccessibility. PMID:26056274

  18. IL-2 production by intestinal lamina propria cells in normal inflamed and cancer-bearing colons.

    PubMed Central

    Pullman, W E; Doe, W F

    1992-01-01

    Biologically significant levels of IL-2 activity were produced by isolated lamina propria mononuclear cells (LPMC) from normal intestine (n = 12), cancer-bearing colons (n = 35) and inflammatory bowel disease (IBD) affected tissue (n = 12). The levels of IL-2 produced were similar for all three sources of LPMC (normal 252 +/- 48 U/ml, IBD-affected mucosa 197 +/- 42 U/ml and colon cancer 285 +/- 43 U/ml). These levels were significantly greater than those produced by peripheral blood mononuclear cells (20 +/- 5 U/ml, P less than 0.01) on a per cell basis. In mucosa from cancer-bearing colons the amount of IL-2 produced by LPMC was unaffected by the invasiveness of the colon cancer. LPMC IL-2 production was markedly suppressed by drugs used in IBD therapy. 5-Aminosalicylic acid (5-ASA) reduced activity in a dose-dependent fashion. At a dose equivalent to the faecal therapeutic level of 0.5 mg/ml activity, IL-2 production by LPMC was suppressed to 3.4% of controls. Similarly, exposure of LPMC to cyclosporin A (CyA) and hydrocortisone (HC) at therapeutic levels reduced IL-2 activity to less than 1% of controls. The major producers of IL-2 activity were shown to be CD3+ T lymphocytes and those bearing the activation markers IL-2R and TFR. Suppression of mucosal IL-2 production represents an important therapeutic mechanism of drugs used in the management of IBD including HC, 5-ASA and CyA. These results suggest that mucosal T cells produce appreciable levels of IL-2 activity that may be important in maintaining immune homeostasis in the normal intestine, provide anti-neoplastic cytotoxic activity and contribute to the inflammatory events that characterize the mucosal lesions of IBD. PMID:1563100

  19. Genome-wide Pathway Analysis Using Gene Expression Data of Colonic Mucosa in Patients with Inflammatory Bowel Disease

    PubMed Central

    Creanza, Teresa M.; Bossa, Fabrizio; Palumbo, Orazio; Maglietta, Rosalia; Ancona, Nicola; Corritore, Giuseppe; Latiano, Tiziana; Martino, Giuseppina; Biscaglia, Giuseppe; Scimeca, Daniela; De Petris, Michele P.; Carella, Massimo; Annese, Vito; Andriulli, Angelo; Latiano, Anna

    2015-01-01

    Background: Ulcerative colitis (UC) and Crohn's disease (CD) share some pathogenetic features. To provide new steps on the role of altered gene expression, and the involvement of gene networks, in the pathogenesis of these diseases, we performed a genome-wide analysis in 15 patients with CD and 14 patients with UC by comparing the RNA from inflamed and noninflamed colonic mucosa. Methods: Two hundred ninety-eight differentially expressed genes in CD and 520 genes in UC were identified. By bioinformatic analyses, 34 pathways for CD, 6 of them enriched in noninflamed and 28 in inflamed tissues, and 19 pathways for UC, 17 in noninflamed and 2 in inflamed tissues, were also highlighted. Results: In CD, the pathways included genes associated with cytokines and cytokine receptors connection, response to external stimuli, activation of cell proliferation or differentiation, cell migration, apoptosis, and immune regulation. In UC, the pathways were associated with genes related to metabolic and catabolic processes, biosynthesis and interconversion processes, leukocyte migration, regulation of cell proliferation, and epithelial-to-mesenchymal transition. Conclusions: In UC, the pattern of inflammation of colonic mucosa is due to a complex interaction network between host, gut microbiome, and diet, suggesting that bacterial products or endogenous synthetic/catabolic molecules contribute to impairment of the immune response, to breakdown of epithelial barrier, and to enhance the inflammatory process. In patients with CD, genes encoding a large variety of proteins, growth factors, cytokines, chemokines, and adhesion molecules may lead to uncontrolled inflammation with ensuing destruction of epithelial cells, inappropriate stimulation of antimicrobial and T cells differentiation, and inflammasome events. PMID:25901971

  20. A 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials.

    PubMed

    Susewind, Julia; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Collnot, Eva-Maria; Schneider-Daum, Nicole; Griffiths, Gareth Wyn; Lehr, Claus-Michael

    2016-01-01

    Oral exposure to nanomaterials is a current concern, asking for innovative biological test systems to assess their safety, especially also in conditions of inflammatory disorders. Aim of this study was to develop a 3D intestinal model, consisting of Caco-2 cells and two human immune cell lines, suitable to assess nanomaterial toxicity, in either healthy or diseased conditions. Human macrophages (THP-1) and human dendritic cells (MUTZ-3) were embedded in a collagen scaffold and seeded on the apical side of transwell inserts. Caco-2 cells were seeded on top of this layer, forming a 3D model of the intestinal mucosa. Toxicity of engineered nanoparticles (NM101 TiO2, NM300 Ag, Au) was evaluated in non-inflamed and inflamed co-cultures, and also compared to non-inflamed Caco-2 monocultures. Inflammation was elicited by IL-1β, and interactions with engineered NPs were addressed by different endpoints. The 3D co-culture showed well preserved ultrastructure and significant barrier properties. Ag NPs were found to be more toxic than TiO2 or Au NPs. But once inflamed with IL-1β, the co-cultures released higher amounts of IL-8 compared to Caco-2 monocultures. However, the cytotoxicity of Ag NPs was higher in Caco-2 monocultures than in 3D co-cultures. The naturally higher IL-8 production in the co-cultures was enhanced even further by the Ag NPs. This study shows that it is possible to mimic inflamed conditions in a 3D co-culture model of the intestinal mucosa. The fact that it is based on three easily available human cell lines makes this model valuable to study the safety of nanomaterials in the context of inflammation. PMID:25738417

  1. Colonic mucosa-associated lymphoid tissue lymphoma identified by chromoendoscopy.

    PubMed

    Seo, Sang-Wook; Lee, Seung-Hwa; Lee, Duck-Joo; Kim, Kwang-Min; Kang, Joon-Koo; Kim, Do-Wan; Lee, Jeong-Hun

    2014-12-28

    Colonic mucosa-associated lymphoid tissue (MALT) lymphomas are a rare occurrence and the definitive treatment has not been established. Solitary or multiple, elevated or polypoid lesions are the usual appearances of MALT lymphoma in the large intestine and sometimes the surface may reveal abnormal vascularity. Herein, we report a case of MALT lymphoma and review the relevant literature. Upon colonoscopy, a suspected pathologic lesion was observed in the proximal transverse colon. The lesion could be distinguished more prominently after using narrow-band imaging mode and indigo carmine-dye spraying chromoendoscopy. Histopathologic examination of this biopsy specimen revealed lymphoepithelial lesions with diffuse proliferation of atypical lymphoid cells effacing the glandular architecture and centrocyte-like cells infiltrating the lamina propria. Immunohistochemical analyses showed that tumor cells were positive for CD20 and Bcl-2e, and negative for CD10, CD23, and Bcl-6. According to Ann-Arbor staging system, the patient had stage IIE. A partial colectomy with dissection of the paracolic lymph nodes was performed. Until now, there is no recurrence of lymphoma at follow-up. PMID:25561821

  2. Colonic mucosa-associated lymphoid tissue lymphoma identified by chromoendoscopy

    PubMed Central

    Seo, Sang-Wook; Lee, Seung-Hwa; Lee, Duck-Joo; Kim, Kwang-Min; Kang, Joon-Koo; Kim, Do-Wan; Lee, Jeong-Hun

    2014-01-01

    Colonic mucosa-associated lymphoid tissue (MALT) lymphomas are a rare occurrence and the definitive treatment has not been established. Solitary or multiple, elevated or polypoid lesions are the usual appearances of MALT lymphoma in the large intestine and sometimes the surface may reveal abnormal vascularity. Herein, we report a case of MALT lymphoma and review the relevant literature. Upon colonoscopy, a suspected pathologic lesion was observed in the proximal transverse colon. The lesion could be distinguished more prominently after using narrow-band imaging mode and indigo carmine-dye spraying chromoendoscopy. Histopathologic examination of this biopsy specimen revealed lymphoepithelial lesions with diffuse proliferation of atypical lymphoid cells effacing the glandular architecture and centrocyte-like cells infiltrating the lamina propria. Immunohistochemical analyses showed that tumor cells were positive for CD20 and Bcl-2e, and negative for CD10, CD23, and Bcl-6. According to Ann-Arbor staging system, the patient had stage IIE. A partial colectomy with dissection of the paracolic lymph nodes was performed. Until now, there is no recurrence of lymphoma at follow-up. PMID:25561821

  3. Efficient gene delivery to the inflamed colon by local administration of recombinant adenoviruses with normal or modified fibre structure

    PubMed Central

    Wirtz, S; Galle, P; Neurath, M

    1999-01-01

    BACKGROUND/AIMS—Replication deficient recombinant adenoviruses represent an efficient means of transferring genes in vivo into a wide variety of dividing and quiescent cells from many different organs. Although the gastrointestinal tract is a potentially attractive target for gene therapy approaches, only a few studies on the use of viral gene transfer vehicles in the gut have been reported. The prospects of using recombinant adenoviruses for gene delivery into epithelial and subepithelial cells of the normal and inflamed colon are here analysed.
METHODS—An E1/E3 deleted recombinant adenovirus (denoted AdCMVβGal) and an adenovirus with modified fibre structure (denoted AdZ.F(pk7)) both expressing the bacterial lacZ gene under the control of a human cytomegalovirus promoter were used for reporter gene expression in vitro and in vivo. β-Galactosidase activity was determined by specific chemiluminescent reporter gene assay.
RESULTS—Intravenous or intraperitoneal injection of AdCMVβGal into healthy Balb/c mice caused strong reporter gene expression in the liver and spleen but not in the colon. In contrast, local administration of AdCMVβGal resulted in high reporter gene expression in colonic epithelial cells and lamina propria mononuclear cells. A local route of adenovirus administration in mice with experimental colitis induced by the hapten reagent trinitrobenzenesulphonic acid was next evaluated. Interestingly, rectal administration of AdCMVβGal caused a higher β-galactosidase activity in isolated lamina propria cells from infected mice with experimental colitis than in those from controls. Furthermore, isolated lamina propria cells from mice with colitis infected in vitro showed a significant increase in reporter gene activity compared with controls. Finally, AdZ.F(pk7) adenoviruses with modified fibre structure produced 10- to 40-fold higher reporter gene activity in spleen T cells and lamina propria mononuclear cells of colitic mice compared with

  4. Carprofen-induced oxidative stress in mitochondria of the colonic mucosa of the dog

    PubMed Central

    Snow, Lynne A.; McConnico, Rebecca S.; Morgan, Timothy W.; Hartmann, Erica; Davidson, Jacqueline R.; Hosgood, Giselle

    2014-01-01

    The purpose of the study was to compare the conductance and mannitol permeability of canine colonic mucosa in response to carprofen or 2,4-dinitrophenol (DNP) with or without tempol pretreatment. Ten colonic mucosa sections per dog were mounted in Ussing chambers. Treatments were done in duplicate. Mucosa was exposed to carprofen (200 μg/mL) or DNP (0.25 mM), both with and without tempol (1 mM) pretreatment. Conductance was calculated every 15 min for 240 min. Mannitol flux was calculated over 3 consecutive 60-minute periods. Histology or electron microscopy was done after exposure. Conductance over time, mannitol flux, frequency of histologic categories, and electron microscopic changes were analyzed for treatment effects. The mean ± standard deviation (SD) conductance over time for carprofen or DNP-treated colons was not significantly different from control regardless of tempol pretreatment. Period 3 mannitol fluxes for carprofen and DNP-treated colon were not significantly different, but were greater than control. Period 3 mannitol flux for tempol + carprofen was significantly less than tempol + DNP-treated colon. Sloughing of cells and erosions were seen in the mucosa of carprofen-treated colon. Mitochondrial damage was seen more often in carprofen-treated than DNP-treated or control colon. Tempol pretreatment resulted in more ruptured mitochondria in the carprofen-treated colon; however, other mitochondrial changes were not significantly affected by tempol pretreatment in either carprofen or DNP treated colon. Treatment with carprofen or DNP increased the mannitol flux, but pretreatment with tempol mitigated the carprofen effect. It is apparent that structural mitochondrial damage occurs in the canine colonic mucosa after carprofen and DNP exposure. PMID:24982549

  5. Demonstration of Trophozoites of G. Lamblia in Ileal Mucosal Biopsy Specimens May Reveal Giardiasis in Patients With Significantly Inflamed Parasite-free Duodenal Mucosa.

    PubMed

    Oberhuber, Georg; Mesteri, Ildiko; Kopf, Wolfram; Müller, Heiko

    2016-09-01

    In the majority of individuals, infestation with trophozoites of Giardia lamblia (synonymous G. duodenalis or G. intestinalis) leads to a self-limited disease. Whereas most duodenal biopsies with chronic giardiasis show little or no inflammatory reaction, some patients may develop a severe disease with significant mucosal inflammation and various degrees of villous blunting. Occasionally, the histologic changes may resemble those of celiac disease. In this paper, we describe 11 patients, 5 of them female, with chronic giardiasis and demonstrable G. lamblia in ileal biopsies. The median age was 45 years (35 to 62 y), with male patients being at least 10 years younger than female patients. All of the duodenal biopsies showed at least mild villous blunting (grading: mild, marked, or total). In the mucosa an increased number of plasma cells and lymphocytes was observed. Furthermore, varying numbers of granulocytes were found in the lamina propria and in the epithelial layer. In 1 case only, the number of intraepithelial lymphocytes was >40/100 epithelial cells thus mirroring the histologic picture of celiac disease with a flat mucosa (with negative celiac disease-specific serological findings). Interestingly enough, all mucosal biopsy specimens from the duodenum were parasite free. Therefore, giardiasis could only be revealed by the demonstration of trophozoites of G. lamblia in biopsy specimens from the terminal ileum, which had been taken simultaneously or several weeks later. In contrast to duodenal biopsies, the ileal mucosa appeared either normal or only mildly inflamed in this setting. All patients but 1 were symptomatic, with chronic diarrhea being the leading symptom. Symptoms resolved after antibiotic therapy. This study demonstrates that giardiasis may be associated with a significant duodenal pathology in biopsy specimens without discernible parasites. In the cases described here infestation with G. lamblia was only proven histologically by examination of

  6. Antioxidant effects of gastrointestinal digested purple carrot extract on the human cells of colonic mucosa.

    PubMed

    Olejnik, Anna; Rychlik, Joanna; Kidoń, Marcin; Czapski, Janusz; Kowalska, Katarzyna; Juzwa, Wojciech; Olkowicz, Mariola; Dembczyński, Radosław; Moyer, Mary Pat

    2016-01-01

    Purple carrot (PC) is a potential dietary constituent, which represents a valuable source of antioxidants and can modulate the reactive oxygen species (ROS) level in the gastrointestinal tract. Antioxidant capacity of a PC extract subjected to digestion process simulated in the artificial alimentary tract, including the stomach, small intestine and colon, was analyzed in normal human cells of colon mucosa. Results indicated that the extract obtained upon passage through the gastrointestinal tract, which could come into contact with the colonic cells in situ, was less potent than the extract, which was not subjected to digestion process. Digested PC extract exhibited intracellular ROS-inhibitory capacity, with 1mg/mL showing the ROS clearance of 18.4%. A 20.7% reduction in oxidative DNA damage due to colon mucosa cells' treatment with digested PC extract was observed. These findings indicate that PC extract is capable of colonic cells' protection against the adverse effects of oxidative stress. PMID:26213078

  7. Mucoadhesive microparticulates based on polysaccharide for target dual drug delivery of 5-aminosalicylic acid and curcumin to inflamed colon.

    PubMed

    Duan, Haogang; Lü, Shaoyu; Gao, Chunmei; Bai, Xiao; Qin, Hongyan; Wei, Yuhui; Wu, Xin'an; Liu, Mingzhu

    2016-09-01

    In this work, thiolated chitosan/alginate composite microparticulates (CMPs) coated by Eudragit S-100 were developed for colon-specific delivery of 5-aminosalicylic acid (5-ASA) and curcumin (CUR), and the use of it as a multi drug delivery system for the treatment of colitis. The physicochemical properties of the CMPs were evaluated. In vitro release was performed in gradually pH-changing medium simulating the conditions of different parts of GIT, and the results showed that the Eudragit S-100 coating has a pH-sensitive release property, which can avoid drug being released at a pH lower than 7. An everted sac method was used to evaluate the mucoadhesion of CMPs. Ex vivo mucoadhesive tests showed CMPs have excellent mucosa adhesion for the colonic mucosa of rats. In vivo treatment effect of enteric microparticulates systems was evaluated in colitis rats. The results showed superior therapeutic efficiency of this drug delivery system for the colitis rats induced by TNBS. Therefore, the enteric microparticulates systems combined the properties of pH dependent delivery, mucoadhesive, and control release, and could be an available tool for the treatment of human inflammatory bowel disease. PMID:27239905

  8. T cell receptor-zeta and granzyme B expression in mononuclear cell infiltrates in normal colon mucosa and colon carcinoma.

    PubMed Central

    Mulder, W M; Bloemena, E; Stukart, M J; Kummer, J A; Wagstaff, J; Scheper, R J

    1997-01-01

    BACKGROUND: Whereas the presence of a lymphoid infiltrate has been associated with a favourable prognosis in colorectal carcinoma, the proliferative and cytotoxic responses of freshly isolated tumour infiltrating lymphocytes are frequently impaired. In mice, tumour induced immune suppression has been associated with a decreased expression of the zeta-chain of the T cell receptor (TCR)-CD3 complex, and loss of mRNA for granzyme B. AIM: To compare the expression of TCR-zeta and granzyme B in lymphocytes infiltrating normal colonic mucosa and Duke's A and D colorectal carcinomas. SPECIMENS: Paraffin wax embedded normal (n = 10) and malignant colonic mucosa (seven Dukes's A, nine Dukes's D). METHOD: Immunohistochemistry. RESULTS: The numbers of TCR-zeta + lymphocytes decreased from normal mucosa to Dukes's D carcinomas. In contrast, granzyme B+ lymphocytes were more frequent in Dukes's A carcinomas than in normal mucosa, but disappeared from advanced stage tumours. Granzyme B expressing cells were mainly CD3- (natural killer/lymphokine activated killer cells) in normal mucosa, but CD3+ in tumours, indicating the presence of activated cytotoxic T lymphocytes. In vitro culture of tumour infiltrating lymphocytes rapidly restored the expression of both molecules. CONCLUSION: The frequency of TCR-zeta + and granzyme B+ lymphocytes is decreased in advanced stage colorectal carcinomas. The restoration of expression during in vitro stimulation suggests the presence of tumour derived suppressive factors in situ. Images PMID:9155587

  9. Variability of spectra of laser-induced fluorescence of colonic mucosa: its significance for fluorescence detection of colonic neoplasia.

    PubMed

    Chwirot, Barbara W; Kowalska, Małgorzata; Płóciennik, Natalia; Piwiński, Mariusz; Michniewicz, Zbigniew; Chwirot, Stanisław

    2003-05-01

    To determine the extent of a natural variability of the spectra of the autofluorescence and its significance for a reproducibility of different approaches typically used in studies on fluorescence detection of colonic lesions. Two independent series of experiments have been conducted during three years in the same laboratory. Macroscopic tissue specimens obtained during operations of patients with colonic cancers were studied in vitro. The tissues were excited using UV lines of c.w. He-Cd laser and pulsed nitrogen laser and the autofluorescence spectra were recorded for areas visually diagnosed as normal or pathologically changed mucosa. Natural variability of the autofluorescence spectra of colonic tissues seems to be most important factor limiting sensitivity and specificity of the diagnostic algorithms. The mean fluorescence spectra obtained for normal mucosa and its neoplastic lesions differ significantly but the differences are difficult to observe because of the high natural variability among the individual spectra. Further studies of biological basis of the colonic autofluorescence are necessary for a progress in the field of fluorescence detection of colonic neoplastic lesions. PMID:15244272

  10. Autofluorescence of normal and tumor mucosa of human colon: a comprehensive analysis

    NASA Astrophysics Data System (ADS)

    Bottiroli, Giovanni F.; Marchesini, Renato; Croce, Anna C.; Dal Fante, Marco; Cuzzoni, Carolina; Di Palma, Silvana; Spinelli, Pasquale

    1993-08-01

    Both 'in vivo' and 'ex vivo' spectrofluorometric studies of neoplastic and non-neoplastic mucosa of human colon have been carried out, in order to verify the potentials of tissue natural fluorescence as a possible parameter to distinguish normal from diseased tissues, Spectrofluorometric analysis performed at colonoscopy on patients affected by neoplasia, showed that adenocarcinoma, adenoma and non-neoplastic mucosa differ in the fluorescence emissions. The results have been interpreted according to the data obtained on cryostatic sections from biopsies by means of a microspectrofluorometric analysis carried out on each histological component.

  11. LINE-1 hypomethylation in normal colon mucosa is associated with poor survival in Chinese patients with sporadic colon cancer.

    PubMed

    Zhuo, Changhua; Li, Qingguo; Wu, Yuchen; Li, Yiwei; Nie, Jia; Li, Dawei; Peng, Junjie; Lian, Peng; Li, Bin; Cai, Guoxiang; Li, Xinxiang; Cai, Sanjun

    2015-09-15

    Genetic and epigenetic pathways are not independent in colorectal cancer (CRC) carcinogenesis. We aimed to determine the influence of various molecular features on Chinese patients' colon cancer-specific survival (CCSS). Various genetic and epigenetic modifications were detected in paired tumor and normal mucosa tissue samples. The prognostic variables regarding patient CCSS were determined. Overall, 127 patients, including 83 males and 44 females, completed a median follow-up of 65 (3-85) months. A mean LINE-1 methylation rate of 64.62% (range, 9.45-86.93) was observed. Hypermethylation at the hMLH1 gene promoter was detected in 26 (20.47%) patients. KRAS was mutated in 52 (40.94%) patients. Sixteen (12.60%) patients were confirmed as microsatellite instability (MSI)-High, and 76 (59.84%) were found to have loss of heterozygosity at 18q. The LINE-1 methylation level, MSI status, perineural invasion and distant metastases were confirmed as independent prognostic factors for patient CCSS. A stratified survival analysis further revealed that certain subgroups of patients with LINE-1 hypomethylation had significantly worse survival (all p < 0.05). Our data revealed that both genetic and epigenetic abnormalities can concurrently exist during colonic tumorigenesis. As a global epigenetic change, LINE-1 hypomethylation in normal colon mucosa might be associated with a worse outcome in certain Chinese patients with colon cancer. PMID:26172297

  12. LINE-1 hypomethylation in normal colon mucosa is associated with poor survival in Chinese patients with sporadic colon cancer

    PubMed Central

    Wu, Yuchen; Li, Yiwei; Nie, Jia; Li, Dawei; Peng, Junjie; Lian, Peng; Li, Bin; Cai, Guoxiang; Li, Xinxiang; Cai, Sanjun

    2015-01-01

    Genetic and epigenetic pathways are not independent in colorectal cancer (CRC) carcinogenesis. We aimed to determine the influence of various molecular features on Chinese patients' colon cancer-specific survival (CCSS). Various genetic and epigenetic modifications were detected in paired tumor and normal mucosa tissue samples. The prognostic variables regarding patient CCSS were determined. Overall, 127 patients, including 83 males and 44 females, completed a median follow-up of 65 (3–85) months. A mean LINE-1 methylation rate of 64.62% (range, 9.45–86.93) was observed. Hypermethylation at the hMLH1 gene promoter was detected in 26 (20.47%) patients. KRAS was mutated in 52 (40.94%) patients. Sixteen (12.60%) patients were confirmed as microsatellite instability (MSI)-High, and 76 (59.84%) were found to have loss of heterozygosity at 18q. The LINE-1 methylation level, MSI status, perineural invasion and distant metastases were confirmed as independent prognostic factors for patient CCSS. A stratified survival analysis further revealed that certain subgroups of patients with LINE-1 hypomethylation had significantly worse survival (all p < 0.05). Our data revealed that both genetic and epigenetic abnormalities can concurrently exist during colonic tumorigenesis. As a global epigenetic change, LINE-1 hypomethylation in normal colon mucosa might be associated with a worse outcome in certain Chinese patients with colon cancer. PMID:26172297

  13. An exploration of the microrheological environment around the distal ileal villi and proximal colonic mucosa of the possum (Trichosurus vulpecula).

    PubMed

    Lim, Y F; Williams, M A K; Lentle, R G; Janssen, P W M; Mansel, B W; Keen, S A J; Chambers, P

    2013-04-01

    Multiple particle-tracking techniques were used to quantify the thermally driven motion of ensembles of naked polystyrene (0.5 µm diameter) microbeads in order to determine the microrheological characteristics around the gut mucosa. The microbeads were introduced into living ex vivo preparations of the wall of the terminal ileum and proximal colon of the brushtail possum (Trichosurus vulpecula). The fluid environment surrounding both the ileal villi and colonic mucosa was heterogeneous; probably comprising discrete viscoelastic regions suspended in a continuous Newtonian fluid of viscosity close to water. Neither the viscosity of the continuous phase, the elastic modulus (G') nor the sizes of viscoelastic regions varied significantly between areas within 20 µm and areas more than 20 µm from the villous mucosa nor from the tip to the sides of the villous mucosa. The viscosity of the continuous phase at distances further than 20 µm from the colonic mucosa was greater than that at the same distance from the ileal villous mucosa. Furthermore, the estimated sizes of viscoelastic regions were significantly greater in the colon than in the ileum. These findings validate the sensitivity of the method and call into question previous hypotheses that a contiguous layer of mucus envelops all intestinal mucosa and restricts diffusive mass transfer. Our findings suggest that, in the terminal ileum and colon at least, mixing and mass transfer are governed by more complex dynamics than were previously assumed, perhaps with gel filtration by viscoelastic regions that are suspended in a Newtonian fluid. PMID:23389898

  14. An exploration of the microrheological environment around the distal ileal villi and proximal colonic mucosa of the possum (Trichosurus vulpecula)

    PubMed Central

    Lim, Y. F.; Williams, M. A. K.; Lentle, R. G.; Janssen, P. W. M.; Mansel, B. W.; Keen, S. A. J.; Chambers, P.

    2013-01-01

    Multiple particle-tracking techniques were used to quantify the thermally driven motion of ensembles of naked polystyrene (0.5 µm diameter) microbeads in order to determine the microrheological characteristics around the gut mucosa. The microbeads were introduced into living ex vivo preparations of the wall of the terminal ileum and proximal colon of the brushtail possum (Trichosurus vulpecula). The fluid environment surrounding both the ileal villi and colonic mucosa was heterogeneous; probably comprising discrete viscoelastic regions suspended in a continuous Newtonian fluid of viscosity close to water. Neither the viscosity of the continuous phase, the elastic modulus (G’) nor the sizes of viscoelastic regions varied significantly between areas within 20 µm and areas more than 20 µm from the villous mucosa nor from the tip to the sides of the villous mucosa. The viscosity of the continuous phase at distances further than 20 µm from the colonic mucosa was greater than that at the same distance from the ileal villous mucosa. Furthermore, the estimated sizes of viscoelastic regions were significantly greater in the colon than in the ileum. These findings validate the sensitivity of the method and call into question previous hypotheses that a contiguous layer of mucus envelops all intestinal mucosa and restricts diffusive mass transfer. Our findings suggest that, in the terminal ileum and colon at least, mixing and mass transfer are governed by more complex dynamics than were previously assumed, perhaps with gel filtration by viscoelastic regions that are suspended in a Newtonian fluid. PMID:23389898

  15. Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer

    PubMed Central

    2014-01-01

    Background A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient’s gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response. Methods A set of 98 paired adjacent mucosa and tumor tissues from colorectal cancer (CRC) patients and 50 colon mucosa from healthy donors (246 samples in total) were included in this work. RNA extracted from each sample was hybridized in Affymetrix chips Human Genome U219. Functional relationships between genes were inferred by means of systems biology using both transcriptional regulation networks (ARACNe algorithm) and protein-protein interaction networks (BIANA software). Results Here we report a transcriptomic analysis revealing a number of genes activated in adjacent mucosa from CRC patients, not activated in mucosa from healthy donors. A functional analysis of these genes suggested that this active reaction of the adjacent mucosa was related to the presence of the tumor. Transcriptional and protein-interaction networks were used to further elucidate this response of normal gut in front of the tumor, revealing a crosstalk between proteins secreted by the tumor and receptors activated in the adjacent colon tissue; and vice versa. Remarkably, Slit family of proteins activated ROBO receptors in tumor whereas tumor-secreted proteins transduced a cellular signal finally activating AP-1 in adjacent tissue. Conclusions The systems-level approach provides new insights into the micro-ecology of colorectal tumorogenesis. Disrupting this intricate molecular network of cell-cell communication and pro-inflammatory microenvironment could be a therapeutic target in CRC patients. PMID:24597571

  16. Morphological and morphometric measurements in colorectal mucosa of subjects at increased risk for colonic neoplasia.

    PubMed

    Richter, A; Yang, K; Richter, F; Lynch, H T; Lipkin, M

    1993-10-15

    Measurements of intermediate biomarkers have recently increased, attempting to provide useful information about cancer risk. We report morphological findings in rectal mucosal biopsies from patients at low risk and at high risk for colorectal cancer. Rectal biopsies were analyzed from fourteen Seventh-Day Adventist (SDA) subjects at low risk and from twenty-seven members of families with hereditary nonpolyposis colonic cancer (HNPCC) at higher risk. The following measurements were made on rectal crypts: length of crypts, numbers of cells, diameter of the surface, middle and base of the crypts and infiltration of inflammatory cells into the lamina propria. Findings indicated morphological differences in normal-appearing rectal mucosa of individuals in the HNPCC group compared with SDA subjects (P < 0.05). They included shorter crypts with fewer epithelial cells and increased cellular infiltration in the mucosa of HNPCC subjects compared with SDA subjects, suggesting minimal inflammation, and an early stage of crypt atrophy in the rectal mucosa of subjects at higher risk for colonic neoplasia. PMID:8287373

  17. The role of acetylcholine in the regulation of ion transport by rat colon mucosa

    PubMed Central

    Browning, J. G.; Hardcastle, Jacqueline; Hardcastle, P. T.; Sanford, P. A.

    1977-01-01

    1. Acetylcholine increases the potential difference across rat proximal colon both in vivo and in vitro. 2. There is a sigmoid relationship between the change in potential difference and the logarithm of the dose of acetylcholine. The dose—response curve is shifted to the left by neostigmine and to the right by atropine, suggesting that the action of acetylcholine is mediated by a muscarinic type of receptor. 3. The dose-response curve for acetylcholine in vivo is not altered by the ganglion-blocking agents hexamethonium and pentolinium, suggesting a direct effect of this transmitter on the colon. 4. Acetylcholine causes an increase in potential difference, a small decrease in resistance and hence a rise in the current generated by both normal and stripped everted sacs of rat colon. 5. In the absence of sodium, the calculated current change produced by acetylcholine is reduced, and the removal of chloride has a similar inhibitory effect. The absence of bicarbonate does not significantly affect the response. 6. Acetylcholine virtually abolished net sodium movement and induced net chloride secretion and these changes accounted for the increased short-circuit current. 7. Acetylcholine had no effect on oxygen consumption by rings of colon. 8. Tracts staining for acetylcholinesterase were observed running from the submucous plexus towards the mucosal epithelium. 9. This study shows that acetylcholine can influence ion movement by rat colonic mucosa and suggests that the autonomic nervous system might be involved in the regulation of transport mechanisms in this tissue. ImagesPlate 1 PMID:592212

  18. Zinc sulphate attenuates chloride secretion in human colonic mucosae in vitro.

    PubMed

    Medani, Mekki; Bzik, Victoria A; Rogers, Ailin; Collins, Danielle; Kennelly, Rory; Winter, Des C; Brayden, David J; Baird, Alan W

    2012-12-01

    Zinc's usefulness in the treatment of diarrhoea is well established as an addition to oral rehydration. Mechanisms of action of zinc have been explored in intestinal epithelia from rodents and in cell lines. The aim was to examine how zinc alters ion transport and signal transduction in human colon in vitro. Voltage clamped colonic sheets obtained at the time of surgical resection were used to quantify ion transport responses to established secretagogues. Nystatin permeabilisation was used to study basolaterally-sited ion channels. Direct actions of zinc were determined using preparations of colonic crypts isolated from human mucosal sheets. Electrophysiological measurements revealed zinc to be an inhibitor of electrogenic ion transport stimulated by forskolin, PGE(2), histamine and carbachol in isolated human colonic epithelium. Basolateral addition of zinc sulphate had no direct effect on the epithelium. To further outline the mechanism of action, levels of secondary intracellular messengers (3', 5'-cyclic adenosine monophosphate; cAMP) were determined in isolated colonic crypts, and were found to be reduced by zinc sulphate. Finally, indirect evidence from nystatin-permeabilised mucosae further suggested that zinc inhibits basolateral K(+) channels, which are critical for transepithelial Cl(-) secretion linked to water flux. Anti-secretory, and therefore anti-diarrhoeal, actions of exogenous zinc are due, at least in part, to direct basolateral epithelial K(+) channel inhibition. PMID:23022335

  19. Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota

    PubMed Central

    2014-01-01

    Background The microbiota of the mammalian gastrointestinal (GI) tract consists of diverse populations of commensal bacteria that interact with host physiological function. Dysregulating these populations, through exogenous means such as antibiotics or dietary changes, can have adverse consequences on the health of the host. Studies from laboratories such as ours have demonstrated that exposure to psychological stressors disrupts the population profile of intestinal microbiota. To date, such studies have primarily focused on prolonged stressors (repeated across several days) and have assessed fecal bacterial populations. It is not known whether shorter stressors can also impact the microbiota, and whether colonic mucosa-associated populations can also be affected. The mucosa-associated microbiota exist in close proximity to elements of the host immune system and the two are tightly interrelated. Therefore, alterations in these populations should be emphasized. Additionally, stressors can induce differential responses in anxiety-like behavior and corticosterone outputs in variant strains of mice. Thus, whether stressor exposure can have contrasting effects on the colonic microbiota in inbred C57BL/6 mice and outbred CD-1 mice was also examined. Results In the present study, we used high throughput pyrosequencing to assess the effects of a single 2-hour exposure to a social stressor, called social disruption (SDR), on colonic mucosa-associated microbial profiles of C57BL/6 mice. The data indicate that exposure to the stressor significantly changed the community profile and significantly reduced the relative proportions of two genera and one family of highly abundant intestinal bacteria, including the genus Lactobacillus. This finding was confirmed using a quantitative real-time polymerase chain reaction (qPCR) technique. The use of qPCR also identified mouse strain-specific differences in bacterial abundances. L. reuteri, an immunomodulatory species, was decreased in

  20. Grain-rich diets altered the colonic fermentation and mucosa-associated bacterial communities and induced mucosal injuries in goats

    PubMed Central

    Ye, Huimin; Liu, Junhua; Feng, Panfei; Zhu, Weiyun; Mao, Shengyong

    2016-01-01

    Remarkably little information is available about the impact of high-grain (HG) feeding on colonic mucosa-associated bacteria and mucosal morphology. In the present study, 12 male goats were randomly assigned to either a hay diet (n = 6) or an HG diet (65% grain; n = 6) to characterise the changes in the composition of the bacterial community in colonic mucosa and the mucosal morphology of the colon. The results showed that HG feeding decreased the colonic pH and increased the concentrations of total short chain fatty acids and lipopolysaccharides in colonic digesta. The principal coordinate analysis results showed that the HG diet altered the colonic mucosal bacterial communities, with an increase in the abundance of genus Blautia and a decrease in the abundance of genera Bacillus, Enterococcus, and Lactococcus. The HG-fed goats showed sloughing of the surface layer epithelium, intercellular tight junction erosion, cell mitochondrial damage, and upregulation of the relative mRNA expression of IL-2 and IFN-γ in colonic mucosa. Collectively, our data indicate that HG feeding induced changes in colonic mucosal morphology and cytokines expression that might be caused by excessive fermentation and dramatic shifts in the bacterial populations in the colon. PMID:26841945

  1. Electrical properties of pig colonic mucosa measured during early post-natal development.

    PubMed Central

    Hénin, S; Smith, M W

    1976-01-01

    Microvillar membrane (Vm) and transmural (Vt) potential differences were measured in proximal colon taken from pigs at birth and up to 10 days of age. 2. Vm remained independent of the age of the animal provided it was measured in the absence of methionine. The over-all mean was -43-3 mV. Adding methionine to fluid bathing the mucosal surface of new-born pig colon caused a 9-8 mV depolarization of Vm and a 6-7 mV increase in Vt. These effects, which were Na+-dependent, were not seen in the 10-day-old animal. 3. Substituting SO4(2-) for Cl- in methionine-free medium caused a hyperpolarization in Vm. Increasing the concentration of K+ caused corresponding depolarization. Substituting choline for Na+ had no effect on VmCl- and K+ movement across the microvillar membrane together account for the bulk of the measured membrane potential. These results apply to all stages of development. 4. Na+ uptake across the microvillar membrane of the new-born pig colon was increased in the presence of methionine. This effect disappeared in older animals. Na+ uptake in the absence of methionine doubled during the first 24 h of post-natal life. This increase was maintained using colons taken from older animals. 5. Methionine depolarization of Vm in the new-born pig colon is probably caused by the electrogenic influx of Na+. The ability of the colon to actively concentrate methionine within tis mucosa disappears at the same time as methionine ceases to affect Vm and Vt. It is suggested that methionine and Na+ form a ternary complex with a carrier in the brush border of the new-born pig colon and that this carrier is lost or modified during early post-natal development. PMID:994037

  2. Analysis of the depolarizing properties of normal and adenomatous polyps in colon mucosa for the early diagnosis of precancerous lesions

    NASA Astrophysics Data System (ADS)

    Ortega-Quijano, Noé; Fanjul-Vélez, Félix; de Cos-Pérez, Jesús; Arce-Diego, José Luis

    2011-09-01

    Optical characterization of biological tissues by means of polarimetric techniques is an area of growing interest. Polarized light can be used for malignant neoplasms detection. To our knowledge, few studies have so far focused on lesions that are prone to result in cancer. In this work we present a polarimetric study of depolarization in prepathological tissues. Specifically, we will focus on premalignant lesions in human colon due to their clinical relevance. Colonic adenoma, the potential precursor of malignant adenocarcinoma, provokes significant structural modifications in colon mucosa that affect light depolarization. The depolarizing properties of normal and adenomatous polyps mucosa are compared. The average linear degree of polarization is shown to present a strong dependence with the precancerous state of the colonic tissue. This method has the potential to enable an early diagnosis of colon cancer.

  3. Analysis of normal and diseased colon mucosa using ultraviolet resonance Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Boustany, Nada N.; Manoharan, Ramasamy; Dasari, Ramachandra R.; Feld, Michael S.

    1996-04-01

    Ultraviolet resonance Raman (UVRR) spectroscopy was used to characterize normal and diseased colon mucosa in vitro. A tunable mode-locked Titanium:Sapphire laser operating at 76 MHz was used to irradiate normal and diseased colon tissue samples with 251 nm light generated from the third harmonic of the fundamental radiation. The Raman scattered light was collected and analyzed using a 1 meter spectrometer fitted with a UV coated, liquid nitrogen cooled CCD detector. The measured spectra show prominent bands that correspond to those of known tissue constituents including nucleic acids, aromatic amino acids and lipids. Using the Raman lineshapes measured from pure solutions of nucleotides, tryptophan, tyrosine, FAD, and from lipid-rich serosal fat, the colon spectra were modeled by a least square fitting algorithm whereby the colon spectra were assumed to be a linear combination of the pure biochemical lineshapes. The relative Raman scattering cross section of each biochemical was determined so that the relative concentration of each compound with respect to the others, could be extracted from a given tissue spectrum.

  4. Uropathogenic E. coli Exploit CEA to Promote Colonization of the Urogenital Tract Mucosa.

    PubMed

    Muenzner, Petra; Kengmo Tchoupa, Arnaud; Klauser, Benedikt; Brunner, Thomas; Putze, Johannes; Dobrindt, Ulrich; Hauck, Christof R

    2016-05-01

    Attachment to the host mucosa is a key step in bacterial pathogenesis. On the apical surface of epithelial cells, members of the human carcinoembryonic antigen (CEA) family are abundant glycoproteins involved in cell-cell adhesion and modulation of cell signaling. Interestingly, several gram-negative bacterial pathogens target these receptors by specialized adhesins. The prototype of a CEACAM-binding pathogen, Neisseria gonorrhoeae, utilizes colony opacity associated (Opa) proteins to engage CEA, as well as the CEA-related cell adhesion molecules CEACAM1 and CEACAM6 on human epithelial cells. By heterologous expression of neisserial Opa proteins in non-pathogenic E. coli we find that the Opa protein-CEA interaction is sufficient to alter gene expression, to increase integrin activity and to promote matrix adhesion of infected cervical carcinoma cells and immortalized vaginal epithelial cells in vitro. These CEA-triggered events translate in suppression of exfoliation and improved colonization of the urogenital tract by Opa protein-expressing E. coli in CEA-transgenic compared to wildtype mice. Interestingly, uropathogenic E. coli expressing an unrelated CEACAM-binding protein of the Afa/Dr adhesin family recapitulate the in vitro and in vivo phenotype. In contrast, an isogenic strain lacking the CEACAM-binding adhesin shows reduced colonization and does not suppress epithelial exfoliation. These results demonstrate that engagement of human CEACAMs by distinct bacterial adhesins is sufficient to blunt exfoliation and to promote host infection. Our findings provide novel insight into mucosal colonization by a common UPEC pathotype and help to explain why human CEACAMs are a preferred epithelial target structure for diverse gram-negative bacteria to establish a foothold on the human mucosa. PMID:27171273

  5. Uropathogenic E. coli Exploit CEA to Promote Colonization of the Urogenital Tract Mucosa

    PubMed Central

    Muenzner, Petra; Kengmo Tchoupa, Arnaud; Klauser, Benedikt; Brunner, Thomas; Putze, Johannes; Dobrindt, Ulrich; Hauck, Christof R.

    2016-01-01

    Attachment to the host mucosa is a key step in bacterial pathogenesis. On the apical surface of epithelial cells, members of the human carcinoembryonic antigen (CEA) family are abundant glycoproteins involved in cell-cell adhesion and modulation of cell signaling. Interestingly, several gram-negative bacterial pathogens target these receptors by specialized adhesins. The prototype of a CEACAM-binding pathogen, Neisseria gonorrhoeae, utilizes colony opacity associated (Opa) proteins to engage CEA, as well as the CEA-related cell adhesion molecules CEACAM1 and CEACAM6 on human epithelial cells. By heterologous expression of neisserial Opa proteins in non-pathogenic E. coli we find that the Opa protein-CEA interaction is sufficient to alter gene expression, to increase integrin activity and to promote matrix adhesion of infected cervical carcinoma cells and immortalized vaginal epithelial cells in vitro. These CEA-triggered events translate in suppression of exfoliation and improved colonization of the urogenital tract by Opa protein-expressing E. coli in CEA-transgenic compared to wildtype mice. Interestingly, uropathogenic E. coli expressing an unrelated CEACAM-binding protein of the Afa/Dr adhesin family recapitulate the in vitro and in vivo phenotype. In contrast, an isogenic strain lacking the CEACAM-binding adhesin shows reduced colonization and does not suppress epithelial exfoliation. These results demonstrate that engagement of human CEACAMs by distinct bacterial adhesins is sufficient to blunt exfoliation and to promote host infection. Our findings provide novel insight into mucosal colonization by a common UPEC pathotype and help to explain why human CEACAMs are a preferred epithelial target structure for diverse gram-negative bacteria to establish a foothold on the human mucosa. PMID:27171273

  6. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa.

    PubMed

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-03-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (I sc). Subsequent I sc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. I sc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation. PMID:26038704

  7. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa

    PubMed Central

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-01-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (Isc). Subsequent Isc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. Isc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation. PMID:26038704

  8. Altered Interactions between the Gut Microbiome and Colonic Mucosa Precede Polyposis in APCMin/+ Mice

    PubMed Central

    Son, Joshua S.; Khair, Shanawaj; Pettet, Donald W.; Ouyang, Nengtai; Tian, Xinyu; Zhang, Yuanhao; Zhu, Wei; Mackenzie, Gerardo G.; Robertson, Charles E.; Ir, Diana; Frank, Daniel N.; Rigas, Basil; Li, Ellen

    2015-01-01

    Mutation of the adenomatous polyposis coli (APC gene), an early event in the adenoma-carcinoma sequence, is present in 70-80% of sporadic human colorectal adenomas and carcinomas. To test the hypothesis that mutation of the APC gene alters microbial interactions with host intestinal mucosa prior to the development of polyposis, culture-independent methods (targeted qPCR assays and Illumina sequencing of the 16S rRNA gene V1V2 hypervariable region) were used to compare the intestinal microbial composition of 30 six-week old C57BL/6 APCMin/+ and 30 congenic wild type (WT) mice. The results demonstrate that similar to 12-14 week old APCMin/+ mice with intestinal neoplasia, 6 week old APCMin/+ mice with no detectable neoplasia, exhibit an increased relative abundance of Bacteroidetes spp in the colon. Parallel mouse RNA sequence analysis, conducted on a subset of proximal colonic RNA samples (6 APCMin/+, 6 WT) revealed 130 differentially expressed genes (DEGs, fold change ≥ 2, FDR <0.05). Hierarchical clustering of the DEGs was carried out by using 1-r dissimilarity measurement, where r stands for the Pearson correlation, and Ward minimum variance linkage, in order to reduce the number of input variables. When the cluster centroids (medians) were included along with APC genotype as input variables in a negative binomial (NB) regression model, four of seven mouse gene clusters, in addition to APC genotype, were significantly associated with the increased relative abundance of Bacteroidetes spp. Three of the four clusters include several downregulated genes encoding immunoglobulin variable regions and non-protein coding RNAs. These results support the concept that mutation of the APC gene alters colonic-microbial interactions prior to polyposis. It remains to be determined whether interventions directed at ameliorating dysbiosis in APCMin/+mice, such as through probiotics, prebiotics or antibiotics, could reduce tumor formation. PMID:26121046

  9. Exercise associated genes in rat colon mucosa: upregulation of ornithin decarboxylase-1.

    PubMed

    Buehlmeyer, K; Doering, F; Daniel, H; Schulz, T; Michna, H

    2007-05-01

    Epidemiology has revealed that physical activity is an important lifestyle factor that reduces the risk of colon cancer. However, the underlying mechanisms of this protective effect have so far not been defined. The aim of this study was to identify molecular targets of physical activity in rat colon mucosa by employing our voluntary exercise model. Twenty male rats underwent a 12-week exercise program, with 9 additional rats serving as a control group. Running distances, body weights and heart weights as measures of physical adaptations were recorded, and changes in mRNA steady-state levels of marker genes involved in vascularization (VEGF, HIF-1 alpha, ODC-1), apoptosis (Bcl-2, PPAR gamma) and prostaglandin synthesis (COX-2) were determined by qRT-PCR. The four housekeeping genes GAPDH, beta-actin, 18S and ALDA served as reference genes. Recorded running distances showed great inter-individual differences resulting in three different groups of low (L-EX, < 2629 m/night; n=5), moderate (M-EX, 3003 - 7458 m/night; n=10) and high (H-EX, > 8314 m/night; n=5) physical activity. The M-EX and H-EX group revealed significant (p<0.05) adaptive changes with an increase in heart mass per kg body weight and a decrease in mean body weight. Amongst the marker genes studied by mRNA expression analysis only ODC-1 appears to be differentially expressed. Its 1.8-fold increased steady-state mRNA level in the H-EX group suggests that synthesis of polyamines may be increased by physical activity. This new finding could provide a link between extensive physical activity and its protective effects on colon cancer development. PMID:17111318

  10. IGF-1 Gene Expression in Rat Colonic Mucosa After Different Exercise Volumes

    PubMed Central

    Buehlmeyer, Katja; Doering, Frank; Daniel, Hannelore; Petridou, Anatoli; Mougios, Vassilis; Schulz, Thorsten; Michna, Horst

    2007-01-01

    The evidence is increasing for a close link between the insulin/insulin-like growth factor (IGF) system and colon cancer prevention by physical exercise. To reveal exercise-induced alterations in colon mucosa, gene expression of IGF-1 and related genes and serum IGF-1 were investigated. Twenty male Wistar rats performed a 12 week voluntary exercise program. Nine rats served as the control group. Gene expression of IGF-1, IGF-1 receptor (IGF-1R) and IGF-binding protein 3 (IGF-BP3) were quantified by real-time RT-PCR. Circulating IGF-1 was analyzed exercise volume-dependent. Based on 3 distinguished groups with low (L-EX, <2629 m·night-1), medium (M-EX, 3003-7458 m·night-1) and high exercise volume (H-EX, >8314 m·night-1), we observed lower serum IGF-1 levels (P < 0.05) in all exercise groups as compared to the control group and IGF-1 levels declined proportional to the increase in exercise volume. A significant (p < 0.05) positive correlation was found between IGF-1 concentration and body mass (r = 0.50) and a significant negative correlation exists between body mass and exercise volume (r = -0.50). Significant differences in colonic mRNA levels of IGF-1, IGF-1R and IGF-BP3 could not be observed. Based on our data we propose that the exercise as well as the body mass reduction leads to a decrease in circulating IGF-1 and this might represent a prime link to colon cancer prevention. Key pointsThere were significantly lower serum IGF-1 levels in all exercise groups as compared to the control group.GF-1 levels declined proportional to the increase in exercise volume.A significant positive correlation was found between IGF-1 concentration and body mass and a significant negative correlation was found between body mass and exercise volume.Significant differences in colonic mRNA levels of IGF-1, IGF-1R and IGF-BP3 could not be observed. PMID:24149475

  11. IGF-1 Gene Expression in Rat Colonic Mucosa After Different Exercise Volumes.

    PubMed

    Buehlmeyer, Katja; Doering, Frank; Daniel, Hannelore; Petridou, Anatoli; Mougios, Vassilis; Schulz, Thorsten; Michna, Horst

    2007-01-01

    The evidence is increasing for a close link between the insulin/insulin-like growth factor (IGF) system and colon cancer prevention by physical exercise. To reveal exercise-induced alterations in colon mucosa, gene expression of IGF-1 and related genes and serum IGF-1 were investigated. Twenty male Wistar rats performed a 12 week voluntary exercise program. Nine rats served as the control group. Gene expression of IGF-1, IGF-1 receptor (IGF-1R) and IGF-binding protein 3 (IGF-BP3) were quantified by real-time RT-PCR. Circulating IGF-1 was analyzed exercise volume-dependent. Based on 3 distinguished groups with low (L-EX, <2629 m·night(-1)), medium (M-EX, 3003-7458 m·night(-1)) and high exercise volume (H-EX, >8314 m·night(-1)), we observed lower serum IGF-1 levels (P < 0.05) in all exercise groups as compared to the control group and IGF-1 levels declined proportional to the increase in exercise volume. A significant (p < 0.05) positive correlation was found between IGF-1 concentration and body mass (r = 0.50) and a significant negative correlation exists between body mass and exercise volume (r = -0.50). Significant differences in colonic mRNA levels of IGF-1, IGF-1R and IGF-BP3 could not be observed. Based on our data we propose that the exercise as well as the body mass reduction leads to a decrease in circulating IGF-1 and this might represent a prime link to colon cancer prevention. Key pointsThere were significantly lower serum IGF-1 levels in all exercise groups as compared to the control group.GF-1 levels declined proportional to the increase in exercise volume.A significant positive correlation was found between IGF-1 concentration and body mass and a significant negative correlation was found between body mass and exercise volume.Significant differences in colonic mRNA levels of IGF-1, IGF-1R and IGF-BP3 could not be observed. PMID:24149475

  12. Cytological picture of the oral mucosa in patients with gastric and colon cancer.

    PubMed

    Kędra, Bożena; Chomczyk, Monika; Złotkowski, Marcin; Stokowska, Wanda; Borsuk, Agnieszka; Bicz, Mieczysław; Pietruska, Małgorzata; Tokajuk, Grażyna; Charkiewicz, Radosław; Czajka, Piotr; Chyczewski, Lech; Zimnoch, Lech; Kędra, Bogusław

    2012-01-01

    The incidence of malignant gastrointestinal cancers in Poland has been constantly growing, which has led to an intensification of the search for new markers of the early clinical stage of this disease. The oral cavity,as the first part of the gastrointestinal tract, has a very important role. The oral cavity presents symptoms of both typically stomatological and systemic diseases. Oral cancers, benign or malignant, may originate and grow in any of the tissues of the mouth, and within this small area they may be of varied clinical, histological and biological features. These can be lesions typically observed in the oral cavity, but also characteristic of cases where the symptoms occur both in the mouth and in other body parts. The aim of this study was to present a cytological picture of the oral mucosa in patients with gastric and colon cancer and to compare the cytological picture with that obtained from a group of patients with no cancer, using the Papanicolaou classification and the Bethesda system. The study was conducted in 126 patients treated surgically in the II General and Gastroenterological Surgery Clinic between 2006 and 2008. All patients were divided into two groups based on the type of lesions. In both of the studied groups, more than half of the patients did not present any abnormalities in the mucosa of the mouth, lips and cheeks in the physical examination. None of the patients had erosion, ulceration or lesions typical of leukoplakia or lichen planus. No malignant cells were detected in either of the studied groups, and there were no well-defined lesions found in the oral cavity that would distinguish the patients with gastrointestinal cancer. PMID:23042267

  13. Role of Escherichia coli O157:H7 Virulence Factors in Colonization at the Bovine Terminal Rectal Mucosa

    PubMed Central

    Sheng, Haiqing; Lim, Ji Youn; Knecht, Hannah J.; Li, Jie; Hovde, Carolyn J.

    2006-01-01

    The human pathogen Escherichia coli O157:H7 causes hemorrhagic colitis and life-threatening sequelae and transiently colonizes healthy cattle at the terminal rectal mucosa. This study analyzed virulence factors important for the clinical manifestations of human E. coli O157:H7 infection for their contribution to the persistence of E. coli in cattle. The colonizing ability of E. coli O157:H7 was compared with those of nonpathogenic E. coli K-12 and isogenic deletion mutants missing Shiga toxin (Stx), the adhesin intimin, its receptor Tir, hemolysin, or the ∼92-kb pO157. Fully ruminant steers received a single rectal application of one E. coli strain so that effects of mucosal attachment and survival at the terminal rectum could be measured without the impact of bacterial passage through the entire gastrointestinal tract. Colonization was monitored by sensitive recto-anal junction mucosal swab culture. Nonpathogenic E. coli K-12 did not colonize as well as E. coli O157:H7 at the bovine terminal rectal mucosa. The E. coli O157:H7 best able to persist had intimin, Tir, and the pO157. Strains missing even one of these factors were recovered in lower numbers and were cleared faster than the wild type. In contrast, E. coli O157:H7 strains that were missing Stx or hemolysin colonized like the wild type. For these three strains, the number of bacteria increased between days 1 and 4 postapplication and then decreased slowly. In contrast, the numbers of noncolonizing strains (K-12, Δtir, and Δeae) decreased from the day of application. These patterns consistently predicted long-term colonization or clearance of the bacteria from the bovine terminal rectal mucosa. PMID:16861656

  14. Neighborhood analysis of low magnification structures (glands) in healthy, adenomatous, and carcinomatous colon mucosa.

    PubMed

    Kayser, K; Shaver, M; Modlinger, F; Postl, K; Moyers, J J

    1986-05-01

    A new algorithm analyzing neighborhood conditions of adenomatous tissue is is introduced. Using O'Callaghan's definition of neighborhoods, a graph theory approach for measuring histomorphological structures can be created as follows: glands are defined as vertices and the coherence of neighboring glands as edges. The procedure leads to an unoriented, well-defined graph which contains information usually not measurable by conventional morphometric analysis. Measurements on healthy mucosa, tubulo-villous adenoma and highly to moderately differentiated adenocarcinoma of colon revealed statistically significant differences (p less than or equal to 0.05) for the following parameters: number of vertices, number of edges, frequency distribution of n-stars and of n-closed paths. Correct separation and reclassification of 83% of cases could be carried out using discriminant analysis. 11/15 cases (73%) could be classified correctly in a prospective group based upon the learning set. The significance of these findings for automatic pattern recognition in histopathology is discussed. PMID:3737471

  15. Contribution of the Collagen-Binding Proteins of Streptococcus mutans to Bacterial Colonization of Inflamed Dental Pulp

    PubMed Central

    Nomura, Ryota; Ogaya, Yuko; Nakano, Kazuhiko

    2016-01-01

    Streptococcus mutans is a major pathogen of dental caries. Collagen-binding proteins (CBPs) (approximately 120 kDa), termed Cnm and Cbm, are regarded as important cell surface antigens related to the adherence of S. mutans to collagenous tissue. Furthermore, CBP-positive S. mutans strains are associated with various systemic diseases involving bacteremia, such as infective endocarditis. Endodontic infection is considered to be an important cause of bacteremia, but little is known regarding the presence of S. mutans in dental pulp tissue. In the present study, the distribution and virulence of S. mutans in dental pulp tissues were investigated by focusing on CBPs. Adhesion and invasion properties of various S. mutans strains were analyzed using human dental pulp fibroblasts (HDPFs). CBP-positive strains had a significantly higher rate of adhesion to HDPFs compared with CBP-defective isogenic mutant strains (P<0.001). In addition, CBP-positive strains induced HDPF proliferation, which is a possible mechanism related to development of hyperplastic pulpitis. The distribution of S. mutans strains isolated from infected root canal specimens was then analyzed by PCR. We found that approximately 50% of the root canal specimens were positive for S. mutans. Approximately 20% of these strains were Cnm-positive, while no Cbm-positive strains were isolated. The Cnm-positive strains isolated from the specimens showed adhesion to HDPFs. Our results suggest that CBP-positive S. mutans strains exhibit high colonization in dental pulp. This could be a possible virulence factor for various systemic diseases. PMID:27442266

  16. An In Vitro Model to Evaluate the Impact of the Soluble Factors from the Colonic Mucosa of Collagenous Colitis Patients on T Cells: Enhanced Production of IL-17A and IL-10 from Peripheral CD4+ T Cells

    PubMed Central

    Nyhlin, Nils; Wickbom, Anna; Bohr, Johan; Hultgren, Olof; Hultgren Hörnquist, Elisabeth

    2014-01-01

    Soluble factors from intestinal mucosal cells contribute to immune homeostasis in the gut. We have established an in vitro model to investigate the regulatory role of soluble factors from inflamed intestinal mucosa of collagenous colitis (CC) patients in the differentiation of T cells. Peripheral blood CD4+ T cells from healthy donors were polyclonally activated in the presence of conditioned medium (CM) generated from denuded biopsies (DNB) or isolated lamina propria mononuclear cells (LPMCs) from mucosal biopsies from CC patients compared to noninflamed controls, to determine proliferation and secretion of cytokines involved in T-cell differentiation. Compared to controls, we observed significantly increased production of the proinflammatory cytokines IFN-γ, IL-17A, IL-6, and IL-1β and the anti-inflammatory cytokines IL-4 and IL-10 in the presence of CC-DNB-CM. The most pronounced effect of CC-LPMC-CM on peripheral CD4+ T cells was a trend towards increased production of IL-17A and IL-10. A trend towards reduced inhibition of T-cell proliferation was noted in the presence of CC-DNB-CM. In conclusion, our in vitro model reveals implications of soluble factors from CC colonic mucosa on peripheral T cells, enhancing their production of both pro- and anti-inflammatory cytokines. PMID:25332518

  17. Chronic infection with Toxoplasma gondii induces death of submucosal enteric neurons and damage in the colonic mucosa of rats.

    PubMed

    Góis, Marcelo Biondaro; Hermes-Uliana, Catchia; Barreto Zago, Maísa Cristina; Zanoni, Jacqueline Nelisis; da Silva, Aristeu Vieira; de Miranda-Neto, Marcílio Hubner; Almeida Araújo, Eduardo José de; Sant'Ana, Débora de Mello Gonçales

    2016-05-01

    Intestinal epithelial secretion is coordinated by the submucosal plexus (SMP). Chemical mediators from SMP regulate the immunobiological response and direct actions against infectious agents. Toxoplasma gondii is a worldwide parasite that causes toxoplasmosis. This study aimed to determine the effects of chronic infection with T. gondii on the morphometry of the mucosa and the submucosal enteric neurons in the proximal colon of rats. Male adult rats were distributed into a control group (n = 10) and an infected group (n = 10). Infected rats received orally 500 oocysts of T. gondii (ME-49). After 36 days, the rats were euthanized and samples of the proximal colon were processed for histology to evaluate mucosal thickness in sections. Whole mounts were stained with methylene blue and subjected to immunohistochemistry to detect vasoactive intestinal polypeptide. The total number of submucosal neurons decreased by 16.20%. Vasoactive intestinal polypeptide-immunoreactive neurons increased by 26.95%. Intraepithelial lymphocytes increased by 62.86% and sulfomucin-producing goblet cells decreased by 22.87%. Crypt depth was greater by 43.02%. It was concluded that chronic infection with T. gondii induced death and hypertrophy in the remaining submucosal enteric neurons and damage to the colonic mucosa of rats. PMID:26902605

  18. Inhibitory effect of succinic acid on epithelial cell proliferation of colonic mucosa in rats.

    PubMed

    Inagaki, Akiko; Ichikawa, Hirofumi; Sakata, Takashi

    2007-08-01

    Microbial breakdown of carbohydrates in the large intestine mainly produces short-chain fatty acids (SCFA). SCFA stimulate epithelial cell proliferation of the digestive tract in vivo. Succinic acid sometimes accumulates in the colonic lumen. However, the effect of succinic acid on colonic epithelial cell proliferation is unknown. Thus, we planned to clarify the influence of succinic acid on colonic epithelial cell proliferation in vivo. We continuously administered infusate with or without succinic acid (100 mM) into the distal colon of rats for 6 d and measured accumulated mitosis per crypt of distal colon of these rats. Succinic acid infused into rat colons significantly inhibited colonic cell proliferation and reduced crypt size. These results clearly indicated the inhibitory effects of succinic acid on colonic epithelial cell proliferation in vivo. PMID:17934246

  19. Claudin-3 and occludin tissue content in the glands of colonic mucosa with and without a fecal stream.

    PubMed

    Martinez, Carlos Augusto Real; de Campos, Fabio Guilherme Caserta Maryssael; de Carvalho, Viviel Rodrigo José; de Castro Ferreira, Caroline; Rodrigues, Murilo Rocha; Sato, Daniela Tiemi; Pereira, José Aires

    2015-04-01

    The synthesis of the proteins of the apical tight junctions (TJs) depends on a continuous supply of short-chain fatty acids (SCFAs) in colonic epithelium. No studies have evaluated the tissue contents of the TJs proteins in colon segments devoid of a fecal stream. To evaluate the contents of claudin-3 and occludin in the glands of colonic mucosa devoid of a fecal stream. Forty-five rats underwent a diversion of the fecal stream via a left side colostomy and distal mucous fistula. Three groups of 15 animals each were sacrificed at 6, 12 or 18 weeks after surgery. The presence and severity of colitis were defined by histology and inflammation grading scales, respectively. The expression of claudin-3 and occludin were evaluated by immunohistochemistry, and their contents were evaluated by computer-assisted image analysis. Mann-Whitney and Kruskal-Wallis tests were used to evaluate the results at a significance level of 5% (p < 0.05). The colonic epithelium without a fecal stream had a higher degree of inflammation. Colonic glands without a fecal stream showed a reduction in claudin-3 content independent of the time and reduction in occludin content after 12 weeks of intestinal exclusion. The content of claudin-3 and occludin were mainly reduced at the apical surfaces of the colon glands, whereas segments retaining the fecal stream were maintained. The content of claudin-3 was not reduced with time, although the levels of occludin were reduced after 6 weeks and did not vary thereafter. Deficiencies in SCFAs decreased the content of claudin-3 and occludin in colonic glands with the areas of worst inflammation, confirming the importance of an adequate supply of SCFAs in maintaining the integrity of TJ proteins. PMID:25649016

  20. Effect of fermented oatmeal soup on the cholesterol level and the Lactobacillus colonization of rat intestinal mucosa.

    PubMed

    Molin, G; Andersson, R; Ahrné, S; Lönner, C; Marklinder, I; Johansson, M L; Jeppsson, B; Bengmark, S

    1992-04-01

    Rats were fed with freeze-dried oatmeal soup fermented by six different Lactobacillus strains from rat and man; the formula is intended for enteral feeding. The serum cholesterol levels after 10 d were lower for rats eating oatmeal as compared to a commercial product, Biosorb Sond. Colonizing ability of the administered strains were evaluated in vivo. Only Lactobacillus reuteri R21c were able to, effectively, colonizing the mucosa; it represented about 30% of the Lactobacillus population 24 d after termination of the administration. L. reuteri R21c was easily recognized by the ability to produce a yellow pigment on agar plates. The identity was confirmed by carbohydrate fermentations (API 50CH), plasmid pattern and endonuclease restriction analysis of the chromosomal DNA. PMID:1519914

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

    PubMed

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

    2007-06-01

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

  2. Interactions Between Bacteria and the Gut Mucosa: Do Enteric Neurotransmitters Acting on the Mucosal Epithelium Influence Intestinal Colonization or Infection?

    PubMed

    Green, Benedict T; Brown, David R

    2016-01-01

    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 enteric neurons, whose activity is influenced by bacterial pathogens, and their secreted products. Neurotransmitters appear to influence epithelial associations with bacteria in the intestinal lumen. For example, internalization of Salmonella enterica and Escherichia coli O157:H7 into the Peyer's patch mucosa of the small intestine is altered after the inhibition of neural activity with saxitoxin, a neuronal sodium channel blocker. Catecholamine neurotransmitters, such as dopamine and norepinephrine, also alter bacterial internalization in Peyer's patches. In the large intestine, norepinephrine increases the mucosal adherence of E. coli. These neurotransmitter actions are mediated by well-defined catecholamine receptors situated on the basolateral membranes of epithelial cells rather than through direct interactions with luminal bacteria. Investigations of the involvement of neuroepithelial communication in the regulation of interactions between the intestinal mucosa and luminal bacteria will provide novel insights into the mechanisms underlying bacterial colonization and pathogenesis at mucosal surfaces. PMID:26589216

  3. Muc2 Protects against Lethal Infectious Colitis by Disassociating Pathogenic and Commensal Bacteria from the Colonic Mucosa

    PubMed Central

    Bergstrom, Kirk S. B.; Kissoon-Singh, Vanessa; Gibson, Deanna L.; Ma, Caixia; Montero, Marinieve; Sham, Ho Pan; Ryz, Natasha; Huang, Tina; Velcich, Anna; Finlay, B. Brett; Chadee, Kris; Vallance, Bruce A.

    2010-01-01

    Despite recent advances in our understanding of the pathogenesis of attaching and effacing (A/E) Escherichia coli infections, the mechanisms by which the host defends against these microbes are unclear. The goal of this study was to determine the role of goblet cell-derived Muc2, the major intestinal secretory mucin and primary component of the mucus layer, in host protection against A/E pathogens. To assess the role of Muc2 during A/E bacterial infections, we inoculated Muc2 deficient (Muc2−/−) mice with Citrobacter rodentium, a murine A/E pathogen related to diarrheagenic A/E E. coli. Unlike wildtype (WT) mice, infected Muc2−/− mice exhibited rapid weight loss and suffered up to 90% mortality. Stool plating demonstrated 10–100 fold greater C. rodentium burdens in Muc2−/− vs. WT mice, most of which were found to be loosely adherent to the colonic mucosa. Histology of Muc2−/− mice revealed ulceration in the colon amid focal bacterial microcolonies. Metabolic labeling of secreted mucins in the large intestine demonstrated that mucin secretion was markedly increased in WT mice during infection compared to uninfected controls, suggesting that the host uses increased mucin release to flush pathogens from the mucosal surface. Muc2 also impacted host-commensal interactions during infection, as FISH analysis revealed C. rodentium microcolonies contained numerous commensal microbes, which was not observed in WT mice. Orally administered FITC-Dextran and FISH staining showed significantly worsened intestinal barrier disruption in Muc2−/− vs. WT mice, with overt pathogen and commensal translocation into the Muc2−/− colonic mucosa. Interestingly, commensal depletion enhanced C. rodentium colonization of Muc2−/− mice, although colonic pathology was not significantly altered. In conclusion, Muc2 production is critical for host protection during A/E bacterial infections, by limiting overall pathogen and commensal numbers associated with the colonic

  4. Evaluation of intestinal absorption enhancement and local mucosal toxicity of two promoters. I. Studies in isolated rat and human colonic mucosae.

    PubMed

    Maher, Sam; Kennelly, Rory; Bzik, Victoria A; Baird, Alan W; Wang, Xuexuan; Winter, Desmond; Brayden, David J

    2009-11-01

    The effects of two absorption promoters, (sodium caprate (C(10)) and melittin), on intestinal permeability and viability were measured in intact rat and human colonic epithelia mounted in Ussing chambers. Apical-side addition of C(10) (10 mM) and melittin (10-50 microM) rapidly reduced the transepithelial electrical resistance (TEER) and increased the apparent permeability coefficient (Papp) of [(14)C]-mannitol and FITC-dextran-4 kDa (FD4) across colonic mucosae from both species. Effects of C(10) on flux were greater than those of melittin at the concentrations selected. C(10) irreversibly decreased TEER, but the effects of melittin were partially reversible. Enhanced permeability of polar sugars (0.18-70 kDa) in colonic mucosae with C(10) was accompanied by significant release of lactate dehydrogenase (LDH) from the luminal surface as well as by inhibition of electrogenic chloride secretion induced by the muscarinic agonist, carbachol (0.1-10 microM). Although melittin did not alter electrogenic chloride secretion in rat or human colonic mucosae, it caused leakage of LDH from rat tissue. Gross histology and electron microscopy of rat and human colonic mucosae demonstrated that each permeation enhancer can induce colonic epithelial damage at concentrations required to increase marker fluxes. C(10) led to more significant mucosal damage than melittin, characterised by sloughing and mucosal erosion. Overall, these results indicate that while C(10) and melittin increase transport of paracellular flux markers across isolated human and rat colonic mucosae in vitro, these effects are associated with some cytotoxicity. PMID:19737613

  5. Integrated datasets characterize metabolic interactions between mouse’s colonic mucosa, colonic-cecal contents and feces

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pattern of metabolites produced by the gut microbiome comprises a phenotype indicative of the means by which that microbiome affects the gut. We characterized that phenotype by conducting metabolomic analyses of the colonic-cecal contents, comparing that to the metabolite patterns of feces and c...

  6. Colonization by Candida Species of the Oral and Vaginal Mucosa in HIV-Infected and Noninfected Women

    PubMed Central

    Hu, Haihong; Wang, Cuiwei; Hamilton, Pilar; Blackmon, Mandy; Chen, Hui; Calderone, Richard; Li, Dongmei

    2013-01-01

    Abstract Candidiasis in HIV/AIDS patients continues to be a public health problem. Effective antifungal therapies are few in number and have inherent problems such as selecting for drug-resistant strains of Candida species. To evaluate the state of Candida colonization of the oral and vaginal mucosa, we recruited 80 women, both HIV-infected and HIV-uninfected, from the Women's Interagency HIV Study (WIHS). Diet diaries were collected by participants to examine the role of diet on fungal growth. Baseline studies were initially done in participants that followed the colonization of both mucosal sites over 0–90 days. The most common Candida species from both groups of patients were C. albicans and C. glabrata. Among the HIV-infected cohort, the percentage of participants who were positive for Candida spp. was higher than in the HIV-uninfected control group. Furthermore, the frequency of colonization (1 episode versus >1 episode) was also increased in the HIV-infected cohort. These data indicate that Candida species remain an important component of the microbial community in both populations. PMID:23098053

  7. Diagnosis of a submucosal mass at the staple line after sigmoid colon cancer resection by endoscopic cutting-mucosa biopsy.

    PubMed

    Morimoto, Mitsuaki; Koinuma, Koji; Lefor, Alan K; Horie, Hisanaga; Ito, Homare; Sata, Naohiro; Hayashi, Yoshikazu; Sunada, Keijiro; Yamamoto, Hironori

    2016-04-25

    A 48-year-old man underwent laparoscopic sigmoid colon resection for cancer and surveillance colonoscopy was performed annually thereafter. Five years after the resection, a submucosal mass was found at the anastomotic staple line, 15 cm from the anal verge. Computed tomography scan and endoscopic ultrasound were not consistent with tumor recurrence. Endoscopic mucosa biopsy was performed to obtain a definitive diagnosis. Mucosal incision over the lesion with the cutting needle knife technique revealed a creamy white material, which was completely removed. Histologic examination showed fibrotic tissue without caseous necrosis or tumor cells. No bacteria, including mycobacterium, were found on culture. The patient remains free of recurrence at five years since the resection. Endoscopic biopsy with a cutting mucosal incision is an important technique for evaluation of submucosal lesions after rectal resection. PMID:27114752

  8. Diagnosis of a submucosal mass at the staple line after sigmoid colon cancer resection by endoscopic cutting-mucosa biopsy

    PubMed Central

    Morimoto, Mitsuaki; Koinuma, Koji; Lefor, Alan K; Horie, Hisanaga; Ito, Homare; Sata, Naohiro; Hayashi, Yoshikazu; Sunada, Keijiro; Yamamoto, Hironori

    2016-01-01

    A 48-year-old man underwent laparoscopic sigmoid colon resection for cancer and surveillance colonoscopy was performed annually thereafter. Five years after the resection, a submucosal mass was found at the anastomotic staple line, 15 cm from the anal verge. Computed tomography scan and endoscopic ultrasound were not consistent with tumor recurrence. Endoscopic mucosa biopsy was performed to obtain a definitive diagnosis. Mucosal incision over the lesion with the cutting needle knife technique revealed a creamy white material, which was completely removed. Histologic examination showed fibrotic tissue without caseous necrosis or tumor cells. No bacteria, including mycobacterium, were found on culture. The patient remains free of recurrence at five years since the resection. Endoscopic biopsy with a cutting mucosal incision is an important technique for evaluation of submucosal lesions after rectal resection. PMID:27114752

  9. The role of the colonic flora in maintaining a healthy large bowel mucosa.

    PubMed

    Chapman, M A

    2001-03-01

    This work explores the intricate relationships between bacterial products of fermentation, the short chain fatty acids and the effect that these have on the colonic epithelium and the immune system. It confirms that butyrate is a major energy source for the colonic epithelium and there may be a minor epithelial abnormality in the metabolism of butyrate in patients with ulcerative colitis. Immunological studies suggest that butyrate has an effect on lymphocyte activation and inhibits cell proliferation. Possibly, butyrate induces anergy in lymphocytes via an effect on the TCR receptor. This may represent a mechanism whereby colonic bacteria are able to regulate the host immune response. An abnormal response to butyrate may upset the homeostasis between the gut immune system and the colonising bacteria resulting in epithelial unrest and inflammation. PMID:11320933

  10. [THE INFLUENCE OF NANODISPERSE CERIUM DIOXIDE ON ONTOGENETIC CHANGES OF ANTIOXIDANT SYSTEM IN THE MUCOSA OF THE STOMACH AND COLON IN RATS].

    PubMed

    Iefimenko, O Yu; Savchenko, I O; Falalyeyeva, T M; Beregova, T V; Zholobak, N M; Shcherbakov, O B; Malyukin, Yu V; Spivak, M Ya

    2015-01-01

    It was established that with age the content of lipid peroxidation products increased in the mucosa of the stomach: Diene conjugates by 30%, products which react to thiobarbituric acid by 285% and Schif bases by 181%. Nanodisperse cerium dioxide (NCD) reduced the content of lipid peroxidation in the gastric mucosa in old rats: Diene conjugates by 43 %, products which react to thiobarbituric acid by 51% and Schif bases by 44% relative to the control group of rats given age. Similarly, it was established that the content of Diene conjugates increased by 40%, products which react to thiobarbituric acid by 114% and Schif bases by 132% in the mucosa of the colon of old rats. NDC significant reduced the content of products which react to thiobarbituric acid by 69% and Schyf basics by 132%. In the stomach superoxide dismutase (by 43%) and catalase activity (by 24%) decreases with age, while in the colon superoxide dismutase activity increases (by 43%). In the colon NCD significant decreased superoxide dismutase (by 34%) and catalase activity (by 21%) relative to controls. Thus, the NDC restores lipid peroxidation in the gastric mucosa and colon, in which develops oxidative stress with age. PMID:26495735

  11. Simple method for the preparation of single cell suspensions from normal and tumorous rat colonic mucosa.

    PubMed Central

    Perret, V; Lev, R; Pigman, W

    1977-01-01

    Viable single cell suspensions from rat colonic epithelium were obtained by using phosphate buffered saline containing 0-2 M mannitol. The method, which requires no prior enzyme treatment, provides undamaged cells in high yield within one hour. The procedure was also applied to neoplastic rat colonic tissue, which was induced by repeated intrarectal infusion of N-methyl-N-nitrosourea. Comparison between normal and neoplastic cells has shown that the latter have a higher nucleus: cytoplasm ratio and a higher metabolic activity. Images Figure PMID:873323

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

    PubMed

    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. PMID:26480216

  13. Miniaturized camera system for an endoscopic capsule for examination of the colonic mucosa

    NASA Astrophysics Data System (ADS)

    Wippermann, Frank; Müller, Martin; Wäny, Martin; Voltz, Stephan

    2014-09-01

    Todaýs standard procedure for the examination of the colon uses a digital endoscope located at the tip of a tube encasing wires for camera read out, fibers for illumination, and mechanical structures for steering and navigation. On the other hand, there are swallowable capsules incorporating a miniaturized camera which are more cost effective, disposable, and less unpleasant for the patient during examination but cannot be navigated along the path through the colon. We report on the development of a miniaturized endoscopic camera as part of a completely wireless capsule which can be safely and accurately navigated and controlled from the outside using an electromagnet. The endoscope is based on a global shutter CMOS-imager with 640x640 pixels and a pixel size of 3.6μm featuring through silicon vias. Hence, the required electronic connectivity is done at its back side using a ball grid array enabling smallest lateral dimensions. The layout of the f/5-objective with 100° diagonal field of view aims for low production cost and employs polymeric lenses produced by injection molding. Due to the need of at least one-time autoclaving, high temperature resistant polymers were selected. Optical and mechanical design considerations are given along with experimental data obtained from realized demonstrators.

  14. Interaction of Lactobacillus fermentum BGHI14 with Rat Colonic Mucosa: Implications for Colitis Induction

    PubMed Central

    Lukic, Jovanka; Strahinic, Ivana; Milenkovic, Marina; Golic, Natasa; Kojic, Milan; Topisirovic, Ljubisa

    2013-01-01

    The present study was carried out to test the colonic mucosal response of rats to oral supplementation with Lactobacillus fermentum BGHI14 and to correlate the tissue reaction to trinitrobenzenesulfonate (TNBS)-induced colitis with mucosal barrier alterations caused by bacterial ingestion. An immune cell-mediated reaction of healthy colonic tissue was noticed after bacterial feeding. After prolonged bacterial treatment, the observed reaction had retreated to normality, but the mRNA levels of proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) remained elevated. These data point to the chronic low-grade inflammation that could be caused by long-term probiotic consumption. Although no detrimental effects of bacterial pretreatment were noticed in colitic rats, at least in the acute state of disease, the results obtained in our study point to the necessity of reassessment of existing data on the safety of probiotic preparations. Additionally, probiotic effects in experimental colitis models might depend on time coordination of disease induction with treatment duration. PMID:23851097

  15. Xylan-regulated Delivery of Human Keratinocyte Growth Factor-2 to the Inflamed Colon by the Human Anaerobic Commensal Bacterium Bacteroides ovatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of genetically modified bacteria to deliver biologically active molecules directly to the gut has become an increasingly attractive area of investigation. The challenge of regulation of production of the therapeutic molecule and colonization of the bowel led us to investigate Bacteroides ov...

  16. An in vitro model to evaluate the impact of the soluble factors from the colonic mucosa of collagenous colitis patients on T cells: enhanced production of IL-17A and IL-10 from peripheral CD4⁺ T cells.

    PubMed

    Kumawat, Ashok Kumar; Nyhlin, Nils; Wickbom, Anna; Tysk, Curt; Bohr, Johan; Hultgren, Olof; Hörnquist, Elisabeth Hultgren

    2014-01-01

    Soluble factors from intestinal mucosal cells contribute to immune homeostasis in the gut. We have established an in vitro model to investigate the regulatory role of soluble factors from inflamed intestinal mucosa of collagenous colitis (CC) patients in the differentiation of T cells. Peripheral blood CD4(+) T cells from healthy donors were polyclonally activated in the presence of conditioned medium (CM) generated from denuded biopsies (DNB) or isolated lamina propria mononuclear cells (LPMCs) from mucosal biopsies from CC patients compared to noninflamed controls, to determine proliferation and secretion of cytokines involved in T-cell differentiation. Compared to controls, we observed significantly increased production of the proinflammatory cytokines IFN-γ, IL-17A, IL-6, and IL-1β and the anti-inflammatory cytokines IL-4 and IL-10 in the presence of CC-DNB-CM. The most pronounced effect of CC-LPMC-CM on peripheral CD4(+) T cells was a trend towards increased production of IL-17A and IL-10. A trend towards reduced inhibition of T-cell proliferation was noted in the presence of CC-DNB-CM. In conclusion, our in vitro model reveals implications of soluble factors from CC colonic mucosa on peripheral T cells, enhancing their production of both pro- and anti-inflammatory cytokines. PMID:25332518

  17. Expression of the Bitter Taste Receptor, T2R38, in Enteroendocrine Cells of the Colonic Mucosa of Overweight/Obese vs. Lean Subjects

    PubMed Central

    Latorre, Rocco; Huynh, Jennifer; Mazzoni, Maurizio; Gupta, Arpana; Bonora, Elena; Clavenzani, Paolo; Chang, Lin; Mayer, Emeran A.; De Giorgio, Roberto; Sternini, Catia

    2016-01-01

    Bitter taste receptors (T2Rs) are expressed in the mammalian gastrointestinal mucosa. In the mouse colon, T2R138 is localized to enteroendocrine cells and is upregulated by long-term high fat diet that induces obesity. The aims of this study were to test whether T2R38 expression is altered in overweight/obese (OW/OB) compared to normal weight (NW) subjects and characterize the cell types expressing T2R38, the human counterpart of mouse T2R138, in human colon. Colonic mucosal biopsies were obtained during colonoscopy from 35 healthy subjects (20 OW/OB and 15 NW) and processed for quantitative RT-PCR and immunohistochemistry using antibodies to T2R38, chromogranin A (CgA), glucagon like peptide-1 (GLP-1), cholecystokinin (CCK), or peptide YY (PYY). T2R38 mRNA levels in the colonic mucosa of OW/OB were increased (> 2 fold) compared to NW subjects but did not reach statistical significance (P = 0.06). However, the number of T2R38 immunoreactive (IR) cells was significantly increased in OW/OB vs. NW subjects (P = 0.01) and was significantly correlated with BMI values (r = 0.7557; P = 0.001). In both OW/OB and NW individuals, all T2R38-IR cells contained CgA-IR supporting they are enteroendocrine. In both groups, T2R38-IR colocalized with CCK-, GLP1- or PYY-IR. The overall CgA-IR cell population was comparable in OW/OB and NW individuals. This study shows that T2R38 is expressed in distinct populations of enteroendocrine cells in the human colonic mucosa and supports T2R38 upregulation in OW/OB subjects. T2R38 might mediate host functional responses to increased energy balance and intraluminal changes occurring in obesity, which could involve peptide release from enteroendocrine cells. PMID:26866366

  18. MicroRNA profiles in colorectal carcinomas, adenomas and normal colonic mucosa: variations in miRNA expression and disease progression.

    PubMed

    Slattery, Martha L; Herrick, Jennifer S; Pellatt, Daniel F; Stevens, John R; Mullany, Lila E; Wolff, Erica; Hoffman, Michael D; Samowitz, Wade S; Wolff, Roger K

    2016-03-01

    MiRNAs are small, non-protein-coding RNA molecules that regulate gene expression either by post-transcriptionally suppressing mRNA translation or by mRNA degradation. We examine differentially expressed miRNAs in colorectal carcinomas, adenomas and normal colonic mucosa. Data come from population-based studies of colorectal cancer conducted in Utah and the Kaiser Permanente Medical Care Program. A total of 1893 carcinoma/normal-paired samples and 290 adenoma tissue samples were run on the Agilent Human miRNA Microarray V19.0 which contained 2006 miRNAs. We tested for significant differences in miRNA expression between paired carcinoma/adenoma/normal colonic tissue samples. Fewer than 600 miRNAs were expressed in >80% of people for colonic tissue; of these 86.5% were statistically differentially expressed between carcinoma and normal colonic mucosa using a false discovery rate of 0.05. Roughly half of these differentially expressed miRNAs showed a progression in levels of expression from normal to adenoma to carcinoma tissue. Other miRNAs appeared to be altered at the normal to adenoma stage, while others were only altered at the adenoma to carcinoma stage or only at the normal to carcinoma stage. Evaluation of the Agilent platform showed a high degree of repeatability (r = 0.98) and reasonable agreement with the NanoString platform. Our data suggest that miRNAs are highly dysregulated in colorectal tissue among individuals with colorectal cancer; the pattern of disruption varies by miRNA as tissue progresses from normal to adenoma to carcinoma. PMID:26740022

  19. Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora.

    PubMed Central

    Johansson, M L; Molin, G; Jeppsson, B; Nobaek, S; Ahrné, S; Bengmark, S

    1993-01-01

    In vivo colonization by different Lactobacillus strains on human intestinal mucosa of healthy volunteers was studied together with the effect of Lactobacillus administration on different groups of indigenous bacteria. A total of 19 test strains were administered in fermented oatmeal soup containing 5 x 10(6) CFU of each strain per ml by using a dose of 100 ml of soup per day for 10 days. Biopsies were taken from both the upper jejunum and the rectum 1 day before administration was started and 1 and 11 days after administration was terminated. The administration significantly increased the Lactobacillus counts on the jejunum mucosa, and high levels remained 11 days after administration was terminated. The levels of streptococci increased by 10- to 100-fold in two persons, and the levels of sulfite-reducing clostridia in the jejunum decreased by 10- to 100-fold in three of the volunteers 1 day after administration was terminated. In recta, the anaerobic bacterium counts and the gram-negative anaerobic bacterium counts decreased significantly by the end of administration. Furthermore, a decrease in the number of members of the Enterobacteriaceae by 1,000-fold was observed on the rectal mucosa of two persons. Randomly picked Lactobacillus isolates were identified phenotypically by API 50CH tests and genotypically by the plasmid profiles of strains and by restriction endonuclease analysis of chromosomal DNAs.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8439146

  20. Deposits of terminal complement complex (TCC) in muscularis mucosae and submucosal vessels in ulcerative colitis and Crohn's disease of the colon.

    PubMed Central

    Halstensen, T S; Mollnes, T E; Fausa, O; Brandtzaeg, P

    1989-01-01

    Extensively washed, ethanol fixed and paraffin embedded colonic specimens from 15 patients with ulcerative colitis (UC) and nine patients with Crohn's disease (CD) of the colon, ileal specimens from six patients with CD of the ileum, and histologically normal control specimens obtained from 10 patients operated for colonic carcinoma, were examined by immunohistochemistry with a monoclonal antibody specific for a neoepitope in the C9 part of the terminal complement complex (TCC). The submucosal blood vessels in inflammatory bowel disease (IBD) showed significantly more TCC positivity than the controls, and vascular TCC deposition was statistically related (p less than 0.001) to degree of inflammation. Five of the six ileal CD specimens contained likewise vascular TCC deposits. In addition, five UC specimens and one colonic CD specimen contained TCC-positive fibrils in the muscularis mucosae or submucosa. There was no significant difference in vascular TCC deposits between UC and CD. The results suggested that terminal complement activation takes place in the intestinal lesions of IBD. Images Fig. 1 Fig. 2 Fig. 3 PMID:2707635

  1. Epithelial and Mesenchymal Cells in the Bovine Colonic Mucosa Differ in Their Responsiveness to Escherichia coli Shiga Toxin 1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cells in the depth of the crypts in the bovine colon express CD77 molecules that potentially act as receptors for Shiga toxins (Stx). The implication of this finding for the intestinal colonization 25 of cattle with human pathogenic Stx-producing Escherichia coli (STEC) remains undefined. We used f...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 includ...

  4. Inhibition of water absorption and selective damage to human colonic mucosa induced by Shiga toxin-2 are enhanced by Escherichia coli O157:H7 infection.

    PubMed

    Albanese, Adriana; Gerhardt, Elizabeth; García, Hugo; Amigo, Natalia; Cataldi, Angel; Zotta, Elsa; Ibarra, Cristina

    2015-05-01

    Shiga toxin-producing Escherichia coli (STEC) strains are responsible for a variety of clinical syndromes including bloody and non-bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Although multiple serotypes of STEC have been isolated from hemorrhagic colitis cases, E. coli O157:H7 is by far the most prevalent serotype associated with HUS. Shiga toxin is the major virulence factor of E. coli O157:H7 and is responsible for the more severe symptoms of the infection. However, the mechanisms involved in the pathogenesis of diarrhea mediated by Stx2 are not well known. In this study, we have determined the effects of E. coli O157:H7 strain 125/99 wild type (wt) on the human colonic mucosa mounted in an Ussing chamber. In response to 125/99wt, an inhibition of water absorption across human colonic mucosa was observed. Histological sections showed severe necrosis with detachment of the surface epithelium, mononuclear inflammatory infiltrate and loss of goblet cells after 1h of incubation with 125/99wt. These alterations were not observed with the isogenic mutant strain lacking stx2 or with the filter-sterilized culture supernatant from the 125/99wt strain. These results indicate that the cell damages in human colon are induced by Stx2, and that Stx2 production is increased by the interaction with bacterial cells. Identification of host cell-derived factors responsible for increasing Stx2 can lead to new strategies for modulating STEC infections. PMID:25794836

  5. Impact of Eating Probiotic Yogurt on Colonization by Candida Species of the Oral and Vaginal Mucosa in HIV-Infected and HIV-Uninfected Women

    PubMed Central

    Hu, Haihong; Wang, Cuiwei; Hamilton, Pilar R.; Blackmon, Mandy L.; Chen, Hui; Calderone, Richard A.; Li, Dongmei

    2014-01-01

    Background Candidiasis in HIV/AIDS patients continues to be a public health problem. Antifungal therapies are not always effective and may result in complications, such as the development of drug-resistant strains of Candida species. Objectives This study evaluated the impact of probiotic consumption on Candida colonization of the oral and vaginal mucosa. Patients/Methods A pilot study was conducted in 24 women (17 HIV-infected, 7 HIV-uninfected) from the Women's Interagency HIV Study. The women underwent a 60-day initiation period with no probiotic consumption, followed by two 15-day consumption periods, with a different probiotic yogurt (DanActive™ or YoPlus™ yogurt) during each interval. There was a 30-day washout period between the two yogurt consumption periods. Oral and vaginal culture swabs were collected on days 0, 60, 74, and 120. Candida was detected by inoculating each swab in both Sabouraud's dextrose agar with or without chloramphenicol and CHROMagar. Results Less fungal colonization among women was observed when the women consumed probiotic yogurts (54 % of the women had vaginal fungal colonization during the non-probiotic yogurt consumption period, 29 % during the DanActive™ period, and 38 % during YoPlus™ yogurt consumption period), and HIV-infected women had significantly lower vaginal fungal colonization after they consumed DanActive™ yogurt compared to the nonintervention periods (54 vs 29 %, p = 0.03). Conclusions These data are promising, but as expected in a small pilot study, there were some significant changes but also some areas where colonization was not changed. This type of conflicting data is supportive of the need for a larger trial to further elucidate the role of probiotic yogurts in fungal growth in HIV-infected women. PMID:23925786

  6. Computer-aided detection of colonic polyps with level set-based adaptive convolution in volumetric mucosa to advance CT colonography toward a screening modality

    PubMed Central

    Zhu, Hongbin; Duan, Chaijie; Pickhardt, Perry; Wang, Su; Liang, Zhengrong

    2009-01-01

    As a promising second reader of computed tomographic colonography (CTC) screening, the computer-aided detection (CAD) of colonic polyps has earned fast growing research interest. In this paper, we present a CAD scheme to automatically detect colonic polyps in CTC images. First, a thick colon wall representation, ie, a volumetric mucosa (VM) with several voxels wide in general, was segmented from CTC images by a partial-volume image segmentation algorithm. Based on the VM, we employed a level set-based adaptive convolution method for calculating the first- and second-order spatial derivatives more accurately to start the geometric analysis. Furthermore, to emphasize the correspondence among different layers in the VM, we introduced a middle-layer enhanced integration along the image gradient direction inside the VM to improve the operation of extracting the geometric information, like the principal curvatures. Initial polyp candidates (IPCs) were then determined by thresholding the geometric measurements. Based on IPCs, several features were extracted for each IPC, and fed into a support vector machine to reduce false positives (FPs). The final detections were displayed in a commercial system to provide second opinions for radiologists. The CAD scheme was applied to 26 patient CTC studies with 32 confirmed polyps by both optical and virtual colonoscopies. Compared to our previous work, all the polyps can be detected successfully with less FPs. At the 100% by polyp sensitivity, the new method yielded 3.5 FPs/dataset. PMID:20428331

  7. Diets enriched with cereal brans or inulin modulate protein kinase C activity and isozyme expression in rat colonic mucosa.

    PubMed

    Pajari, A M; Oikarinen, S; Gråsten, S; Mutanen, M

    2000-11-01

    The role of dietary fibres in colon carcinogenesis is controversial. To elucidate the mechanisms by which different dietary fibre sources may affect colonic tumour development, we studied the effects of diets enriched with cereal brans or inulin on protein kinase C (PKC) activity and isozyme expression in rat colon. Male Wistar rats (twelve per group) were fed one of the following AIN-93G-based diets (Reeves et al. 1993) for 4 weeks: a non-fibre high-fat diet or one of the four high-fat diets supplemented with either rye, oat or wheat bran or inulin at 100 g/kg diet. The fat concentration (20 g/100 g) and fatty acid composition of the non-fibre high-fat diet was designed to approximate that in a typical Western-type diet. In the proximal colon, rats fed the inulin diet had a significantly higher membrane PKC activity and a higher membrane PKC delta level than rats fed the non-fibre diet In the distal colon, rats fed the inulin and oat bran diets had a higher total PKC activity and a higher membrane PKC beta 2 level than rats fed the wheat-bran diet. Rats in the non-fibre and wheat-bran groups had the lowest concentrations of luminal diacylglycerol. In conclusion, feeding of wheat bran resulted in low distal PKC activity and expression of PKC beta 2, a PKC isozyme related to colonic cell proliferation and increased susceptibility for colon carcinogenesis, which may explain in part the protective effect of wheat bran against tumour development in a number of experimental colon cancer studies. The increase in PKC activity and PKC beta 2 expression by feeding inulin may be a drawback of inulin as a functional food. PMID:11177176

  8. Methylation of MGMT and ADAMTS14 in normal colon mucosa: biomarkers of a field defect for cancerization preferentially targeting elder African-Americans

    PubMed Central

    Alonso, Sergio; Dai, Yuichi; Yamashita, Kentaro; Horiuchi, Shina; Dai, Tomoko; Matsunaga, Akihiro; Sánchez-Muñoz, Rosa; Bilbao-Sieyro, Cristina; Díaz-Chico, Juan Carlos; Chernov, Andrei V.; Strongin, Alex Y.; Perucho, Manuel

    2015-01-01

    Somatic hypermethylation of the O6-methylguanine-DNA methyltransferase gene (MGMT) was previously associated with G > A transition mutations in KRAS and TP53 in colorectal cancer (CRC). We tested the association of MGMT methylation with G > A mutations in KRAS and TP53 in 261 CRCs. Sixteen cases, with and without MGMT hypermethylation, were further analyzed by exome sequencing. No significant association of MGMT methylation with G > A mutations in KRAS, TP53 or in the whole exome was found (p > 0.5 in all comparisons). The result was validated by in silico comparison with 302 CRCs from The Cancer Genome Atlas (TCGA) consortium dataset. Transcriptional silencing associated with hypermethylation and stratified into monoallelic and biallelic. We also found a significant clustering (p = 0.001) of aberrant hypermethylation of MGMT and the matrix metalloproteinase gene ADAMTS14 in normal colonic mucosa of CRC patients. This suggested the existence of an epigenetic field defect for cancerization disrupting the methylation patterns of several loci, including MGMT or ADAMTS14, that may lead to predictive biomarkers for CRC. Methylation of these loci in normal mucosa was more frequent in elder (p = 0.001) patients, and particularly in African Americans (p = 1 × 10−5), thus providing a possible mechanistic link between somatic epigenetic alterations and CRC racial disparities in North America. PMID:25638164

  9. Methylation of MGMT and ADAMTS14 in normal colon mucosa: biomarkers of a field defect for cancerization preferentially targeting elder African-Americans.

    PubMed

    Alonso, Sergio; Dai, Yuichi; Yamashita, Kentaro; Horiuchi, Shina; Dai, Tomoko; Matsunaga, Akihiro; Sánchez-Muñoz, Rosa; Bilbao-Sieyro, Cristina; Díaz-Chico, Juan Carlos; Chernov, Andrei V; Strongin, Alex Y; Perucho, Manuel

    2015-02-20

    Somatic hypermethylation of the O6-methylguanine-DNA methyltransferase gene (MGMT) was previously associated with G > A transition mutations in KRAS and TP53 in colorectal cancer (CRC). We tested the association of MGMT methylation with G > A mutations in KRAS and TP53 in 261 CRCs. Sixteen cases, with and without MGMT hypermethylation, were further analyzed by exome sequencing. No significant association of MGMT methylation with G > A mutations in KRAS, TP53 or in the whole exome was found (p > 0.5 in all comparisons). The result was validated by in silico comparison with 302 CRCs from The Cancer Genome Atlas (TCGA) consortium dataset. Transcriptional silencing associated with hypermethylation and stratified into monoallelic and biallelic. We also found a significant clustering (p = 0.001) of aberrant hypermethylation of MGMT and the matrix metalloproteinase gene ADAMTS14 in normal colonic mucosa of CRC patients. This suggested the existence of an epigenetic field defect for cancerization disrupting the methylation patterns of several loci, including MGMT or ADAMTS14, that may lead to predictive biomarkers for CRC. Methylation of these loci in normal mucosa was more frequent in elder (p = 0.001) patients, and particularly in African Americans (p = 1 × 10-5), thus providing a possible mechanistic link between somatic epigenetic alterations and CRC racial disparities in North America. PMID:25638164

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. Cellular localization of guanylin and uroguanylin mRNAs in human and rat duodenal and colonic mucosa.

    PubMed

    Brenna, Øystein; Furnes, Marianne W; Munkvold, Bjørn; Kidd, Mark; Sandvik, Arne K; Gustafsson, Björn I

    2016-08-01

    Guanylin (GUCA2A/Guca2a/GN) and uroguanylin (GUCA2B/Guca2b/UGN) are expressed in the gastrointestinal tract and have been implicated in ion and fluid homeostasis, satiety, abdominal pain, growth and intestinal barrier integrity. Their cellular sources are debated and include goblet cells, entero-/colonocytes, enteroendocrine (EE) cells and tuft cells. We therefore investigated the cellular sources of GN and UGN mRNAs in human and rat duodenal and colonic epithelium with in situ hybridization (ISH) to determine co-expression with Chromogranin A (CHGA/Chga/CgA; enterochromaffin [EC] cells), defensin alpha 6 (DEFA6/Defa6; Paneth cells), mucin 2 (MUC2/Muc2; goblet cells) and selected tuft cell markers. GUCA2A/Guca2a expression was localized to goblet cells and colonocytes in human and rat colon. In human duodenum, GUCA2A was expressed in Paneth cells and was scarce in villous epithelial cells. In rat duodenum, Guca2a was only localized to goblet cells. Guca2b was focally expressed in rat colon. In human and rat duodenum and in human colon, GUCA2B/Guca2b was expressed in dispersed solitary epithelial cells, some with a tuft cell-like appearance. Neither GUCA2A nor GUCA2B were co-expressed with CHGA in human duodenal cells. Consequently, EC cells are probably not the major source of human GN or UGN but other EE cells as a source of GN or UGN are not entirely excluded. No convincing overlap with tuft cell markers was found. For the first time, we demonstrate the cellular expression of GUCA2B in human duodenum. The specific cellular distribution of both GN and UGN differs between duodenum and colon and between human and rat intestines. PMID:27044258

  12. Dose-dependent stimulatory and inhibitory effects of luminal and serosal n-butyric acid on epithelial cell proliferation of pig distal colonic mucosa.

    PubMed

    Inagaki, Akiko; Sakata, Takashi

    2005-06-01

    Large bowel bacteria convert various carbohydrates into short-chain fatty acids (SCFA). SCFA stimulate epithelial cell proliferation of the large intestine in vivo and inhibit that of various cells in vitro. Supposing that too high concentration of SCFA on the serosal side is responsible for their inhibitory effect in vitro, we studied effects of luminal and serosal n-butyric acid (0, 0.1, 1, or 10 mmol/L, adjusted to neutral pH) on the epithelial cell proliferation rate of pig colonic mucosa in organ culture taking crypt cell production rate (CCPR) as the measure of proliferative activity. With 0 or 0.1 mmol/L n-butyric acid on the serosal side, luminal n-butyric acid increased CCPR at 1.0 mmol/L, and decreased CCPR at 10 mmol/L when compared to the luminal 0 mmol/L control. With 1.0 or 10 mmol/L serosal n-butyric acid, luminal n-butyric acid depressed CCPR dose-dependently. The above results indicated that n-butyric acid stimulated colonic epithelial cell proliferation at low concentration and inhibit it at high concentration with interaction effect to enhance the inhibitory action. The stimulatory effect of a low dose of serosal n-butyric acid may be responsible for the distant trophic effect of SCFA. PMID:16161765

  13. Macrophage and dendritic cell subsets in IBD: ALDH+ cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation

    PubMed Central

    Magnusson, Maria K; Brynjólfsson, Siggeir F; Dige, Anders; Uronen-Hansson, Heli; Börjesson, Lars G.; Bengtsson, Jonas L.; Gudjonsson, Sigurdur; Öhman, Lena; Agnholt, Jørgen; Sjövall, Henrik; Agace, William W; Wick, Mary Jo

    2015-01-01

    Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn’s ileitis, Crohn’s colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14+DRint MQs characterized inflamed intestinal mucosa while total CD141+ or CD1c+ DCs numbers were unchanged. However, CD103+ DCs, including CD141+CD103+ and CD1c+CD103+ DCs, were reduced in inflamed intestine. In MLNs, two CD14− DC populations were identified: CD11cintHLADRhi and CD11chiHLADRint cells. A marked increase of CD11chiHLADRint DC, particularly DRintCD1c+ DCs, characterized MLNs draining inflamed intestine. The fraction of DC and MQ populations expressing aldehyde dehydrogenase (ALDH) activity, reflecting retinoic acid synthesis, in UC colon, both in active disease and remission, were reduced compared to controls and inflamed Crohn’s colon. In contrast, no difference in the frequency of ALDH+ cells among blood precursors was detected between UC patients in remission and non-inflamed controls. This suggests that ALDH activity in myeloid cells in the colon of UC patients, regardless of whether the disease is active or in remission, is influenced by the intestinal environment. PMID:26080709

  14. Impaired Self-Renewal and Increased Colitis and Dysplastic Lesions in Colonic Mucosa of AKR1B8 Deficient Mice

    PubMed Central

    Shen, Yi; Ma, Jun; Yan, Ruilan; Ling, Hongyan; Li, Xiaoning; Yang, Wancai; Gao, John; Huang, Chenfei; Bu, Yiwen; Cao, Yu; He, Yingchun; Wan, Laxiang; Zu, Xuyu; Liu, Jianghua; Huang, Mei Chris; Stenson, William F; Liao, Duan-Fang; Cao, Deliang

    2015-01-01

    Purpose Ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC) is a serious health issue, but etiopathological factors remain unclear. Aldo-keto reductase 1B10 (AKR1B10) is specifically expressed in the colonic epithelium, but down-regulated in colorectal cancer. This study was aimed to investigate the etiopathogenic role of AKR1B10 in UC and CAC. Experimental design UC and CAC biopsies (paraffin-embedded sections) and frozen tissues were collected to examine AKR1B10 expression. Aldo-keto reductase 1B8 (the ortholog of human AKR1B10) knockout (AKR1B8 −/−) mice were produced to estimate its role in the susceptibility and severity of chronic colitis and associated dysplastic lesions, induced by dextran sulfate sodium (DSS) at a low dose (2%). Genome-wide Exome sequencing was used to profile DNA damage in DSS-induced colitis and tumors. Results AKR1B10 expression was markedly diminished in over 90% of UC and CAC tissues. AKR1B8 deficiency led to reduced lipid synthesis from butyrate and diminished proliferation of colonic epithelial cells. The DSS-treated AKR1B8 −/− mice demonstrated impaired injury repair of colonic epithelium and more severe bleeding, inflammation, and ulceration. These AKR1B8 −/− mice had more severe oxidative stress and DNA damage, and dysplasias were more frequent and at a higher grade in the AKR1B8 −/− mice than in wild type mice. Palpable masses were seen in the AKR1B8 −/− mice only, not in wild type. Conclusion AKR1B8 is a critical protein in the proliferation and injury repair of the colonic epithelium and in the pathogenesis of UC and CAC, being a new etiopathogenic factor of these diseases. PMID:25538260

  15. GP41-specific Antibody Blocks Cell-free HIV-1 Transcytosis through Human Rectal Mucosa and Model Colonic Epithelium#

    PubMed Central

    Shen, Ruizhong; Drelichman, Ernesto R.; Bimczok, Diane; Ochsenbauer, Christina; Kappes, John C.; Tudor, Daniela; Bomsel, Morgane; Smythies, Lesley E.; Smith, Phillip D.

    2013-01-01

    Monostratified epithelial cells translocate HIV-1 from the apical to the basolateral surface via vesicular transcytosis. Since acutely transmitted HIV-1 is almost exclusively CCR5-tropic and human intestinal epithelial cells preferentially transcytose CCR5-tropic virus, we established epithelial monolayers using polarized HT-29 cells transduced to express CCR5, and an explant system using normal human rectal mucosa, to characterize biological parameters of epithelial cell transcytosis of HIV-1 and assess antiviral antibody blockade of transcytosis. The amount of cell-free HIV-1 transcytosed through the epithelial monolayer increased linearly in relation to the amount of virus applied to the apical surface, indicating transcytosis efficiency was constant (r2 = 0.9846, P<0.0001). The efficiency of HIV-1 transcytosis ranged between 0.05% and 1.21%, depending on the virus strain, producer cell type and gp120 V1-V3 loop signature. Inoculation of HIV-1 neutralizing antibodies to the immunodominant region (7B2) or the conserved membrane proximal external region (2F5) of gp41 or to cardiolipin (IS4) onto the apical surface of epithelial monolayers prior to inoculation of virus significantly reduced HIV-1 transcytosis. 2F5 was the most potent of these IgG1 mAbs. Dimeric IgA (dIgA) and monomeric IgA (mIgA), but not polymeric IgM, 2F5 antibodies also blocked HIV-1 transcytosis across the epithelium and, importantly, across explanted normal human rectal mucosa, with mIgA substantially more potent than dIgA in effecting transcytosis blockade. These findings underscore the potential role of transcytosis blockade in the prevention of HIV-1 transmission across columnar epithelium such as that of the rectum. PMID:20208001

  16. Roles of alpha and beta carbonic anhydrases of Helicobacter pylori in the urease-dependent response to acidity and in colonization of the murine gastric mucosa.

    PubMed

    Bury-Moné, Stéphanie; Mendz, George L; Ball, Graham E; Thibonnier, Marie; Stingl, Kerstin; Ecobichon, Chantal; Avé, Patrick; Huerre, Michel; Labigne, Agnès; Thiberge, Jean-Michel; De Reuse, Hilde

    2008-02-01

    Carbon dioxide occupies a central position in the physiology of Helicobacter pylori owing to its capnophilic nature, the large amounts of carbon dioxide produced by urease-mediated urea hydrolysis, and the constant bicarbonate supply in the stomach. Carbonic anhydrases (CA) catalyze the interconversion of carbon dioxide and bicarbonate and are involved in functions such as CO(2) transport or trapping and pH homeostasis. H. pylori encodes a periplasmic alpha-CA (alpha-CA-HP) and a cytoplasmic beta-CA (beta-CA-HP). Single CA inactivation and double CA inactivation were obtained for five genetic backgrounds, indicating that H. pylori CA are not essential for growth in vitro. Bicarbonate-carbon dioxide exchange rates were measured by nuclear magnetic resonance spectroscopy using lysates of parental strains and CA mutants. Only the mutants defective in the alpha-CA-HP enzyme showed strongly reduced exchange rates. In H. pylori, urease activity is essential for acid resistance in the gastric environment. Urease activity measured using crude cell extracts was not modified by the absence of CA. With intact CA mutant cells incubated in acidic conditions (pH 2.2) in the presence of urea there was a delay in the increase in the pH of the incubation medium, a phenotype most pronounced in the absence of H. pylori alpha-CA. This correlated with a delay in acid activation of the urease as measured by slower ammonia production in whole cells. The role of CA in vivo was examined using the mouse model of infection with two mouse-adapted H. pylori strains, SS1 and X47-2AL. Compared to colonization by the wild-type strain, colonization by X47-2AL single and double CA mutants was strongly reduced. Colonization by SS1 CA mutants was not significantly different from colonization by wild-type strain SS1. However, when mice were infected by SS1 Delta(beta-CA-HP) or by a SS1 double CA mutant, the inflammation scores of the mouse gastric mucosa were strongly reduced. In conclusion, CA

  17. Pilot clinical study of the effects of ginger root extract on eicosanoids in colonic mucosa of subjects at increased risk for colorectal cancer.

    PubMed

    Zick, Suzanna M; Turgeon, D Kim; Ren, Jianwei; Ruffin, Mack T; Wright, Benjamin D; Sen, Ananda; Djuric, Zora; Brenner, Dean E

    2015-09-01

    Colorectal cancer (CRC) remains a significant cause of mortality. Inhibitors of cyclooxygenase (COX) and thus prostaglandin E2, are promising CRC preventives, but have significant toxicities. Ginger has been shown to inhibit COX, to decrease the incidence and multiplicity of adenomas, and decrease PGE2 concentrations in subjects at normal risk for CRC. This study was conducted to determine the effects of 2.0 g/d of ginger given orally on the levels of PGE2, leukotriene B4 (LTB4), 13-hydroxy-octadecadienoic acids, and 5-, 12-, & 15-hydroxyeicosatetraenoic acid, in the colonic mucosa of subjects at increased risk for CRC. We randomized 20 subjects to 2.0 g/d ginger or placebo for 28 d. At baseline and Day 28, a flexible sigmoidoscopy was used to obtain colon biopsies. A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies, and levels were expressed per amount of protein or free arachidonic acid (AA). There was a significant decrease in AA between baseline and Day 28 (P = 0.05) and significant increase in LTB4 (P = 0.04) when normalized to protein, in subjects treated with ginger versus placebo. No other changes in eicosanoids were observed. There was no difference between the groups in total adverse events (AE; P = 0.06). Ginger lacks the ability to decrease eicosanoid levels in people at increased risk for CRC. Ginger did appear to be both tolerable and safe; and could have chemopreventive effects through other mechanisms. Further investigation should focus on other markers of CRC risk in those at increased CRC risk. PMID:24760534

  18. IL-36α expression is elevated in ulcerative colitis and promotes colonic inflammation.

    PubMed

    Russell, S E; Horan, R M; Stefanska, A M; Carey, A; Leon, G; Aguilera, M; Statovci, D; Moran, T; Fallon, P G; Shanahan, F; Brint, E K; Melgar, S; Hussey, S; Walsh, P T

    2016-09-01

    A role for the IL-36 family of cytokines has been identified in the pathogenesis of psoriasis. Although significant mechanistic overlap can exist between psoriasis and inflammatory bowel disease (IBD), to date there have been no reports investigating the IL-36 family in gastrointestinal inflammation. Here we demonstrate that expression levels of IL-36α are specifically elevated in the colonic mucosa of ulcerative colitis patients. This elevated expression is mirrored in the inflamed colonic mucosa of mice, wherein IL-36 receptor deficiency confirmed this pathway as a mediator of mucosal inflammation. Il36r-/- mice exhibited reduced disease severity in an acute DSS-induced model of colitis in association with decreased innate inflammatory cell infiltration to the colon lamina propria. Consistent with these data, infection with the enteropathogenic bacteria Citrobacter rodentium, resulted in reduced innate inflammatory cell recruitment and increased bacterial colonization in the colons of il36r-/- mice. Il36r-/- mice also exhibited altered T helper cell responses in this model, with enhanced Th17 and reduced Th1 responses, demonstrating that IL-36R signaling also regulates intestinal mucosal T-cell responses. These data identify a novel role for IL-36 signaling in colonic inflammation and indicate that the IL-36R pathway may represent a novel target for therapeutic intervention in IBD. PMID:26813344

  19. Mr 40,000 human colonic epithelial protein expression in colonic mucosa and presence of circulating anti-Mr 40,000 antibodies in cotton top tamarins with spontaneous colitis.

    PubMed Central

    Das, K M; Vecchi, M; Squillante, L; Dasgupta, A; Henke, M; Clapp, N

    1992-01-01

    Saguinus oedipus, Callithrix jacchus, and Saguinus fuscicollis are three species of New World monkeys which develop a form of colitis that is similar to human ulcerative colitis. Only S oedipus, however, develop colon cancer. We examined intestinal tissues from these animals for the presence of an antigen cross reacting to the Mr 40,000 human colonic epithelial protein that acts as an autoantigen in ulcerative colitis. Using an anti-Mr 40,000 monoclonal antibody (7E12H12, IgM isotype), by an immunoperoxidase assay we showed that all colon specimens from S oedipus reacted with 7E12H12; however, the colonic tissue from C jacchus and S fuscicollis did not. In immunotransblot analysis eluted IgG antibody bound to human ulcerative colitis colon (CCA-IgG) reacted with Mr 40,000 protein(s) present in the extracts of colon from S oedipus animals and humans. Small intestinal tissue reacted neither with 7E12H12 nor with CCA-IgG. In S oedipus, the Mr 40,000 protein was localised exclusively to colonic epithelial cells. Preincubation of seven S oedipus colon specimens with eight of 10 sera from animals with acute or chronic colitis and 0 of four sera from animals without colitis almost completely inhibited the binding of 7E12H12 to the colonic epithelium. Four of these 10 sera inhibited the binding of 7E12H12 to the autologous colon. These results show the presence of circulating autoantibodies in S oedipus with colitis against an epitope(s) on Mr 40,000 protein shared by human and S oedipus colon. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1740277

  20. The von Hippel-Lindau (VHL) tumor-suppressor gene is down-regulated by selenium deficiency in Caco-2 cells and rat colon mucosa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To test the hypothesis that selenium affects DNA methylation and hence gene regulation we employed a methylation array (Panomics) in the human colonic epithelial Caco-2 cell model. The array profiles DNA methylation from promoter regions of 82 human genes. After conditioning cells to repeatedly redu...

  1. Bacillus polyfermenticus Ameliorates Colonic Inflammation by Promoting Cytoprotective Effects in Colitic Mice12

    PubMed Central

    Im, Eunok; Choi, Yoon Jeong; Pothoulakis, Charalabos; Rhee, Sang Hoon

    2009-01-01

    Although human consumption of Bacillus polyfermenticus provides several health benefits, the probiotic effect of this bacterium against colonic inflammation has not yet, to our knowledge, been studied. Therefore, we induced colitis in mice by oral or intrarectal administration of dextran sodium sulfate (DSS) or trinitrobenzenosulfonic acid (TNBS), respectively, and investigated the effect of B. polyfermenticus on colitis. We found that mice treated with DSS or TNBS along with B. polyfermenticus had reduced mortality and severity of colitis (weight loss, diarrhea, and mucosal damages) than mice treated with DSS or TNBS alone. B. polyfermenticus also reduced the expression of inflammatory molecules, including chemokine (C-X-C motif) ligand 1, intercellular adhesion molecule, and tumor necrosis factor-α, but enhanced the expression of the antiinflammatory cytokine interleukin-10 in the inflamed mouse colon. Moreover, B. polyfermenticus suppressed apoptosis both in vivo in inflamed colonic mucosa and in vitro in colonic epithelial cells stimulated with apoptosis-inducing agents (FasL or Clostridium difficile Toxin A) when the apoptotic response was determined by a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and cleavage of poly(ADP-ribose) polymerase or caspase-3, respectively. Treating colonic epithelial cells with B. polyfermenticus-conditioned medium (BPCM) enhanced cell proliferation and induced the phosphoinositide 3-kinases/Akt signaling pathway, suggesting that this bacterium can promote epithelial cell proliferation. BPCM also promoted the migration of colonic epithelial cells. These data suggest that B. polyfermenticus ameliorates colonic inflammation by suppressing apoptosis and promoting epithelial cell proliferation and migration. PMID:19675103

  2. The adhesiometer: a simple device to measure adherence of barium sulfate to intestinal mucosa.

    PubMed

    Salomonowitz, E; Frick, M P; Cragg, A H; Lund, G

    1984-04-01

    A simple, inexpensive device assessing barium sulfate adherence to alimentary tract mucosa was tested in an animal study using pigs and dogs. Interaction of gastric, intestinal, and colonic mucosal lining with three different barium preparations was studied. In both pigs and dogs, barium adherence to gastric mucosa was significantly stronger when compared with colonic mucosa. PMID:6608230

  3. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester, a polymeric colon-specific prodrug releasing 5-aminosalicylic acid and benzocaine, ameliorates TNBS-induced rat colitis.

    PubMed

    Nam, Joon; Kim, Wooseong; Lee, Sunyoung; Jeong, Seongkeun; Yoo, Jin-Wook; Kim, Min-Soo; Jung, Yunjin

    2016-06-01

    Local anesthetics have beneficial effects on colitis. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester (Dex-5-ESA), designed as a polymeric colon-specific prodrug liberating 5-ASA and benzocaine in the large intestine, was prepared and its therapeutic activity against colitis was evaluated using a TNBS-induced rat colitis model. Dex-5-ESA liberated 5-ASA and benzocaine in the cecal contents while (bio)chemically stable in the small intestinal contents and mucosa. Oral administration of Dex-5-ESA (equivalent to 10 mg 5-ASA/kg, twice a day) alleviated colonic injury and reduced MPO activity in the inflamed colon. In parallel, pro-inflammatory mediators, COX-2, iNOS and CINC-3, elevated by TNBS-induced colitis, were substantially diminished in the inflamed colon. Dex-5-ESA was much more effective for the treatment of colitis than 5-(4-ethoxycarbonylphenylazo)salicylic acid (5-ESA) that may not deliver benzocaine to the large intestine. Our data suggest that Dex-5-ESA is a polymeric colon-specific prodrug, liberating 5-ASA and benzocaine in the target site (large intestine), probably exerting anti-colitic effects by combined action of 5-ASA and benzocaine. PMID:26377354

  4. Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization.

    PubMed

    Kozakova, Hana; Schwarzer, Martin; Tuckova, Ludmila; Srutkova, Dagmar; Czarnowska, Elzbieta; Rosiak, Ilona; Hudcovic, Tomas; Schabussova, Irma; Hermanova, Petra; Zakostelska, Zuzana; Aleksandrzak-Piekarczyk, Tamara; Koryszewska-Baginska, Anna; Tlaskalova-Hogenova, Helena; Cukrowska, Bozena

    2016-03-01

    Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v 1 using a gnotobiotic mouse model. We showed that Lactobacillus (L.) rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species- and strain-dependent manners. Colonization of germ-free (GF) mice with a mixture of all three strains (Lmix) improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v 1 allergen showed significantly lower levels of allergen-specific IgE, IgG1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor (TGF)-β level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-β after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-β. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans. PMID:25942514

  5. Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization

    PubMed Central

    Kozakova, Hana; Schwarzer, Martin; Tuckova, Ludmila; Srutkova, Dagmar; Czarnowska, Elzbieta; Rosiak, Ilona; Hudcovic, Tomas; Schabussova, Irma; Hermanova, Petra; Zakostelska, Zuzana; Aleksandrzak-Piekarczyk, Tamara; Koryszewska-Baginska, Anna; Tlaskalova-Hogenova, Helena; Cukrowska, Bozena

    2016-01-01

    Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v 1 using a gnotobiotic mouse model. We showed that Lactobacillus (L.) rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species- and strain-dependent manners. Colonization of germ-free (GF) mice with a mixture of all three strains (Lmix) improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v 1 allergen showed significantly lower levels of allergen-specific IgE, IgG1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor (TGF)-β level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-β after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-β. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans. PMID:25942514

  6. Effects of a grape-supplemented diet on proliferation and Wnt signaling in the colonic mucosa are greatest for those over age 50 and with high arginine consumption.

    PubMed

    Holcombe, Randall F; Martinez, Micaela; Planutis, Kestutis; Planutiene, Marina

    2015-01-01

    A diet rich in fruits and vegetables, and a grape-derived compound, resveratrol, have been linked to a reduced incidence of colon cancer. In vitro and in vivo, resveratrol suppresses Wnt signaling, a pathway constitutively activated in over 85 % of colon cancers.Thirty participants were placed on a low resveratrol diet and subsequently allocated to one of three groups ingesting 1/3-to-1 lb (0.15-0.45 kg) of grapes per day for 2 weeks. Dietary information was collected via 24-h recall. Colon biopsies for biomarker analysis were obtained pre- and post-grape and evaluated for the expression of Wnt pathway target genes and for markers of proliferation by RT-PCR and immunohistochemistry.Participants lost an average of 2 · 6 lb (1.2 kg, p = 0 · 0018) during the period of grape ingestion. The expression of CyclinD1 (p < 0 · 01), AXIN2, CD133 (p = 0 · 02) and Ki67 (p = 0 · 002) were all reduced after grape ingestion. Individuals over 50 years of age and those with high dietary arginine consumption had increased basal expression of CyclinD1, AXIN2, cMYC and CD133 (p value range 0 · 04 to <0 · 001) that, following grape ingestion, were reduced to levels seen in younger participants.The reduction in Wnt signaling and mucosal proliferation seen following short-term ingestion of 1/3-1 lb (0.15-0.45 kg) of grapes per day may reduce the risk of mutational events that can facilitate colon carcinogenesis. The potential benefit is most marked for high-risk older individuals and individuals whose diet is high in arginine intake. Dietary grape supplementation may play a role in colon cancer prevention for high-risk individuals. PMID:26085034

  7. Archaea prevalence in inflamed pulp tissues

    PubMed Central

    Efenberger, Magdalena; Agier, Justyna; Pawłowska, Elżbieta

    2015-01-01

    Archaea have been detected in several ecological niches of the human body such as the large intestine, skin, vagina as well as the oral cavity. At present, archaea are recognized as nonpathogenic microorganisms. However, some data indicate that they may be involved in the etiopathogenesis of several diseases, including intestinal diseases as well as oral diseases: periodontitis, peri-implantitis and endodontitis. In this study, on the basis of 16S rRNA gene sequence analysis, we examined whether archaea might be present in inflamed pulp tissues and contribute to the development of endodontic infection. In comparison, we also determined selected bacterial species associated with endodontitis. We detected archaea in 85% of infected endodontic samples. In addition, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola were present in inflamed pulp tissue samples and Treponema denticola occurred with the highest frequency (70%). Further analysis revealed the presence of methanogenic archaea in analyzed samples. Direct sequencing of archaeal 16S rRNA gene PCR products indicated the occurrence of methanogenic archaea in inflamed pulp tissues; phylogenetically most similar were Methanobrevibacter oralis and Methanobrevibacter smithii. Therefore, our results show that methanogenic archaea are present in inflamed pulp tissues and may participate in the development of endodontic infection. PMID:26557034

  8. Microcirculation and micromorphology of healthy and inflamed gingivae.

    PubMed

    Kerdvongbundit, Varunee; Vongsavan, Noppakun; Soo-Ampon, Surin; Hasegawa, Akira

    2003-09-01

    Inflammation changes the microcirculatory and micromorphological dynamics of human gingiva. Laser Doppler flowmetry (LDF) and a replica technique for scanning electron microscopy (SEM) were used to examine the facial soft tissues of six maxillary anterior teeth, before and after treatment, in 12 patients exhibiting clinically healthy tissues and in 12 others with moderate gingivitis. All patients received oral hygiene instructions and scaling. The gingiva in the gingivitis group became healthy within 3 months after treatment. LDF results were recorded at the free gingivae, interdental gingivae, attached gingivae, and alveolar mucosae of the six maxillary anterior teeth. The gingival blood flows in the gingivitis group before treatment were significantly different from those in the healthy gingiva group. Flows were restored to the same level as the healthy gingiva, with no significant difference, at P > 0.01, 3 months after treatment. However, there were significant differences among sites during the same period. In addition, blood flow was reduced to a normal level after the inflammation subsided. Initially, the gingival morphology of the inflamed sites exhibited irregular free gingival margins, in contrast to that of healthy gingivae, which were characterized by rounded margins closely adapted to the tooth. One month post-treatment, the gingivae exhibited a wrinkled appearance, but they had reverted to normal micromorphology by 3 months post-treatment. The replica impression technique can be used to record gingival micromorphology both before and after reduction of inflammation. PMID:14505185

  9. Biomimetic proteolipid vesicles for targeting inflamed tissues.

    PubMed

    Molinaro, R; Corbo, C; Martinez, J O; Taraballi, F; Evangelopoulos, M; Minardi, S; Yazdi, I K; Zhao, P; De Rosa, E; Sherman, M B; De Vita, A; Toledano Furman, N E; Wang, X; Parodi, A; Tasciotti, E

    2016-09-01

    A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and facilitate transport across the endothelial vessel wall. Here, we describe a method that leverages the advantages of bottom-up and top-down strategies to incorporate proteins derived from the leukocyte plasma membrane into lipid nanoparticles. The resulting proteolipid vesicles-which we refer to as leukosomes-retained the versatility and physicochemical properties typical of liposomal formulations, preferentially targeted inflamed vasculature, enabled the selective and effective delivery of dexamethasone to inflamed tissues, and reduced phlogosis in a localized model of inflammation. PMID:27213956

  10. Salmonella Transiently Reside in Luminal Neutrophils in the Inflamed Gut

    PubMed Central

    Loetscher, Yvonne; Wieser, Andreas; Lengefeld, Jette; Kaiser, Patrick; Schubert, Sören; Heikenwalder, Mathias; Hardt, Wolf-Dietrich; Stecher, Bärbel

    2012-01-01

    Background Enteric pathogens need to grow efficiently in the gut lumen in order to cause disease and ensure transmission. The interior of the gut forms a complex environment comprising the mucosal surface area and the inner gut lumen with epithelial cell debris and food particles. Recruitment of neutrophils to the intestinal lumen is a hallmark of non-typhoidal Salmonella enterica infections in humans. Here, we analyzed the interaction of gut luminal neutrophils with S. enterica serovar Typhimurium (S. Tm) in a mouse colitis model. Results Upon S. Tmwt infection, neutrophils transmigrate across the mucosa into the intestinal lumen. We detected a majority of pathogens associated with luminal neutrophils 20 hours after infection. Neutrophils are viable and actively engulf S. Tm, as demonstrated by live microscopy. Using S. Tm mutant strains defective in tissue invasion we show that pathogens are mostly taken up in the gut lumen at the epithelial barrier by luminal neutrophils. In these luminal neutrophils, S. Tm induces expression of genes typically required for its intracellular lifestyle such as siderophore production iroBCDE and the Salmonella pathogenicity island 2 encoded type three secretion system (TTSS-2). This shows that S. Tm at least transiently survives and responds to engulfment by gut luminal neutrophils. Gentamicin protection experiments suggest that the life-span of luminal neutrophils is limited and that S. Tm is subsequently released into the gut lumen. This “fast cycling” through the intracellular compartment of gut luminal neutrophils would explain the high fraction of TTSS-2 and iroBCDE expressing intra- and extracellular bacteria in the lumen of the infected gut. Conclusion In conclusion, live neutrophils recruited during acute S. Tm colitis engulf pathogens in the gut lumen and may thus actively engage in shaping the environment of pathogens and commensals in the inflamed gut. PMID:22493718

  11. Dietary fiber down-regulates colonic tumor necrosis factor alpha and nitric oxide production in trinitrobenzenesulfonic acid-induced colitic rats.

    PubMed

    Rodríguez-Cabezas, Maria Elena; Gálvez, Julio; Lorente, Maria Dolores; Concha, Angel; Camuesco, Desirée; Azzouz, Shamira; Osuna, Antonio; Redondo, Luis; Zarzuelo, Antonio

    2002-11-01

    Previous studies have revealed the beneficial effects exerted by dietary fiber in human inflammatory bowel disease, which were associated with an increased production of SCFA in distal colon. The aim of the present study was to elucidate the probable mechanisms involved in the beneficial effects of a fiber-supplemented diet (5% Plantago ovata seeds) in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis, with special attention to its effects on the production of some of the mediators involved in the inflammatory response, such as tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO). Rats were fed the fiber-supplemented diet for 2 wk before TNBS colitis induction and thereafter until colonic evaluation 1 wk later. The results obtained showed that dietary fiber supplementation facilitated recovery from intestinal insult as evidenced both histologically, by a preservation of intestinal cytoarchitecture, and biochemically, by a significant reduction in colonic myeloperoxidase activity and by restoration of colonic glutathione levels. This intestinal anti-inflammatory effect was associated with lower TNFalpha levels and lower NO synthase activity in the inflamed colon, showing significant differences when compared with nontreated colitic rats. Moreover, the intestinal contents from fiber-treated colitic rats showed a significantly higher production of SCFA, mainly butyrate and propionate. We conclude that the increased production of these SCFA may contribute to recovery of damaged colonic mucosa because they constitute substrates for the colonocyte and, additionally, that they can inhibit the production of proinflammatory mediators, such as TNFalpha and NO. PMID:12421838

  12. Expression of glycoprotein nonmetastatic melanoma protein B in macrophages infiltrating injured mucosa is associated with the severity of experimental colitis in mice.

    PubMed

    Sasaki, Fumisato; Kumagai, Kotaro; Uto, Hirofumi; Takami, Yoichiro; Kure, Takeshi; Tabu, Kazuaki; Nasu, Yuichro; Hashimoto, Shinichi; Kanmura, Shuji; Numata, Masatsugu; Moriuchi, Akihiro; Sakiyama, Toshio; Tsubouchi, Hirohito; Ido, Akio

    2015-11-01

    Glycoprotein nonmetastatic melanoma protein B (Gpnmb) is a transmembrane glycoprotein, which negatively regulates the inflammatory responses of macrophages. However, the role of Gpnmb in intestinal macrophages remains to be fully elucidated. The present study aimed to investigate the expression of Gpnmb and its effects on colonic mucosal injuries associated with dextran sulfate sodium (DSS)‑induced colitis in BALB/c mice, DBA/2J (D2) mice lacking Gpnmb and Gpnmb‑transgenic DBA/2J mice (D2‑gpnmb+). The colonic expression of Gpnmb increased with the severity of DSS‑induced colitis in BALB/c mice, and macrophages infiltrating the inflamed mucosa were found to express Gpnmb. The D2 mice lacking Gpnmb exhibited more severe DSS‑induced colitis, which was accompanied by higher levels of pro‑inflammatory cytokines, including interleukin (IL)‑1β and IL‑6, compared with the D2‑gpnmb+ mice. Following lipopolysaccharide stimulation, macrophages from the D2 mice expressed higher levels of pro‑inflammatory cytokines and lower levels of IL‑10, compared with the D2‑gpnmb+mice. In addition, in the RAW264.7 murine macrophage cell line, knockdown of Gpnmb by small interfering RNA was associated with increased production of pro‑inflammatory cytokines, which were potentially mediated by the extracellular signal‑regulated kinase (ERK) and p38 signaling pathways. The results of the present study indicated that macrophages infiltrating injured mucosa express Gpnmb, and that Gpnmb‑positive macrophages may ameliorate inflammation in the intestinal mucosa by decreasing pro‑inflammatory cytokine production via the ERK and p38 signaling pathways. PMID:26458492

  13. Rectal mucosa in cows' milk allergy.

    PubMed Central

    Iyngkaran, N; Yadav, M; Boey, C G

    1989-01-01

    Eleven infants who were suspected clinically of having cows' milk protein sensitive enteropathy were fed with a protein hydrolysate formula for six to eight weeks, after which they had jejunal and rectal biopsies taken before and 24 hours after challenge with cows' milk protein. When challenged six infants (group 1) developed clinical symptoms and five did not (group 2). In group 1 the lesions developed in both the jejunal mucosa (four infants at 24 hours and one at three days), and the rectal mucosa, and the injury was associated with depletion of alkaline phosphatase activity. Infants in group 2 were normal. It seems that rectal injury that develops as a direct consequence of oral challenge with the protein in reactive infants may be used as one of the measurements to confirm the diagnosis of cows' milk protein sensitive enteropathy. Moreover, ingestion of such food proteins may injure the distal colonic mucosa without affecting the proximal small gut in some infants. PMID:2817945

  14. In GERD patients, mucosal repair associated genes are upregulated in non-inflamed oesophageal epithelium

    PubMed Central

    De Vries, D R; Ter Linde, J J M; Van Herwaarden, M A; Schwartz, M P; Shephard, P; Geng, M M; Smout, A J P M; Samsom, M

    2009-01-01

    Abstract Previous studies addressing the effects of acid reflux and PPI therapy on gene expression in oesophageal epithelium concentrated on inflamed tissue. We aimed to determine changes in gene expression in non-inflamed oesophageal epithelium of GERD patients. Therefore, we included 20 GERD patients with pathological total 24-hr acid exposure of 6–12% and SAP ≥ 95%. Ten patients discontinued PPI treatment (PPI-), 10 took pantoprazole 40 mg bid (PPI+). Ten age/sex-matched healthy controls were recruited. Biopsies were taken from non-inflamed mucosa 6 cm and 16 cm proximal to the squamocolumnar junction (SCJ). Gene expression profiling of biopsies from 6 cm was performed on Human Genome U133 Plus 2.0 arrays (Affymetrix). Genes exhibiting a fold change >1.4 (t-test P-value < 1E– 4) were considered differentially expressed. Results were confirmed by real-time RT-PCR. In PPI- patients, 92 microarray probesets were deregulated. The majority of the corresponding genes were associated with cell–cell contacts, cytoskeletal reorganization and cellular motility, suggesting facilitation of a migratory phenotype. Genes encoding proteins with anti-apoptotic or anti-proliferative functions or stress-protective functions were also deregulated. No probesets were deregulated in PPI+ patients. QPCR analysis of 20 selected genes confirmed most of the deregulations in PPI- patients, and showed several deregulated genes in PPI+ patients as well. In the biopsies taken at 16 cm QPCR revealed no deregulations of the selected genes. We conclude that upon acid exposure, oesophageal epithelial cells activate a process globally known as epithelial restitution: up-regulation of anti-apoptotic, anti-oxidant and migration associated genes. Possibly this process helps maintaining barrier function. PMID:19413890

  15. Carnosinase activity of human gastrointestinal mucosa.

    PubMed Central

    Sadikali, F; Darwish, R; Watson, W C

    1975-01-01

    Carnosinase, the dipeptidase which hydrolyses carnosine and other histidine-containing dipeptides, was assayed in mucosal tissues of the human and of the rat gut. Kinetic properties of the intestinal enzyme were found to be similar to carnosinase of other animal tissues. Little or no activity was detected in human gastric or colonic mucosa, and the levels were lower in duodenal than jejunal mucosa. The distribution of carnosinase is similar to that of the disaccharidases. Mean carnosinase activity was 8-8 units/g weight in 15 patients with histologically normal mucosa compared with 5-7 units in five with villous atrophy. The enzyme levels increased with histological improvement of the mucosa in patients with coeliac disease on a gluten-free diet. Tolerance curves for carnosine and its constitutent amino acids showed malabsorption of the dipeptide in a patient with carnosinase deficiency. It is concluded that the intestinal mucosa has much less hydrolase activity for carnosine than for glycylglycine and other dipeptidases, and the relatively slow hydrolysis appears to be the rate-limiting step in the total absorptive process. PMID:1237444

  16. Genomic Landscape of Colorectal Mucosa and Adenomas.

    PubMed

    Borras, Ester; San Lucas, F Anthony; Chang, Kyle; Zhou, Ruoji; Masand, Gita; Fowler, Jerry; Mork, Maureen E; You, Y Nancy; Taggart, Melissa W; McAllister, Florencia; Jones, David A; Davies, Gareth E; Edelmann, Winfried; Ehli, Erik A; Lynch, Patrick M; Hawk, Ernest T; Capella, Gabriel; Scheet, Paul; Vilar, Eduardo

    2016-06-01

    The molecular basis of the adenoma-to-carcinoma transition has been deduced using comparative analysis of genetic alterations observed through the sequential steps of intestinal carcinogenesis. However, comprehensive genomic analyses of adenomas and at-risk mucosa are still lacking. Therefore, our aim was to characterize the genomic landscape of colonic at-risk mucosa and adenomas. We analyzed the mutation profile and copy number changes of 25 adenomas and adjacent mucosa from 12 familial adenomatous polyposis patients using whole-exome sequencing and validated allelic imbalances (AI) in 37 adenomas using SNP arrays. We assessed for evidence of clonality and performed estimations on the proportions of driver and passenger mutations using a systems biology approach. Adenomas had lower mutational rates than did colorectal cancers and showed recurrent alterations in known cancer driver genes (APC, KRAS, FBXW7, TCF7L2) and AIs in chromosomes 5, 7, and 13. Moreover, 80% of adenomas had somatic alterations in WNT pathway genes. Adenomas displayed evidence of multiclonality similar to stage I carcinomas. Strong correlations between mutational rate and patient age were observed in at-risk mucosa and adenomas. Our data indicate that at least 23% of somatic mutations are present in at-risk mucosa prior to adenoma initiation. The genomic profiles of at-risk mucosa and adenomas illustrate the evolution from normal tissue to carcinoma via greater resolution of molecular changes at the inflection point of premalignant lesions. Furthermore, substantial genomic variation exists in at-risk mucosa before adenoma formation, and deregulation of the WNT pathway is required to foster carcinogenesis. Cancer Prev Res; 9(6); 417-27. ©2016 AACR. PMID:27221540

  17. Effective anaesthesia of the acutely inflamed pulp: part 1. The acutely inflamed pulp.

    PubMed

    Virdee, S S; Seymour, D; Bhakta, S

    2015-10-23

    Achieving profound pulpal anaesthesia in a mandibular molar diagnosed with irreversible pulpitis can be argued to be the most testing of dental anaesthetic challenges. This can be attributed to the technical complexities of conventional techniques and the presence of pulp pathosis. Reasons for why the latter influences the ability to attain pulpal anaesthesia is not yet fully understood, but its frequent occurrence is well documented. In light of overcoming this it has become common practice to prescribe antibiotics, refer onto secondary care or to even commence treatment without appropriately anaesthetising the tooth. Therefore, this two part series aims to help practitioners attain clinically acceptable pulpal anaesthesia in the most testing of scenarios; the acutely inflamed mandibular molar. They should then be able to apply these same principles to other teeth presenting with similar symptoms. This section outlines the clinical presentation and pathophysiology associated with an acutely inflamed pulp, defines what it is to attain pulpal anaesthesia and critically analyses theories as to why these teeth are up to eight times more difficult to anaesthetise than their healthy counterparts. PMID:26494344

  18. Regulation of eotaxin-3/CC chemokine ligand 26 expression by T helper type 2 cytokines in human colonic myofibroblasts.

    PubMed

    Takahashi, K; Imaeda, H; Fujimoto, T; Ban, H; Bamba, S; Tsujikawa, T; Sasaki, M; Fujiyama, Y; Andoh, A

    2013-08-01

    Eotaxins induce the trafficking of eosinophils to the sites of inflammation via CC chemokine receptor 3 (CCR3). In this study, we investigated eotaxin-3/CC chemokine ligand 26 (CCL26) expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for eotaxin-3 expression in human colonic myofibroblasts. Eotaxin-3 mRNA and protein expression was evaluated by real time-polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Eotaxin-3 mRNA expression was elevated significantly in the active lesions of ulcerative colitis (UC) patients. Significant elevations were also observed in the active lesions of Crohn's disease (CD) patients, but this was significantly lower than that detected in the active UC lesions. There were no significant increases in the inactive lesions of UC or CD patients. Colonic myofibroblasts were identified as a major source of eotaxin-3 in the colonic mucosa, and interleukin (IL)-4 and IL-13 enhanced eotaxin-3 mRNA and protein expression significantly in these cells. There was a significant positive correlation between mucosal eotaxin-3 and IL-4 mRNA expression in the active lesions of IBD patients. The IL-4- and IL-13-induced eotaxin-3 mRNA expression was regulated by the signal transducer and activator of transcription-6 (STAT-6) and suppressor of cytokine signalling (SOCS)1-mediated pathways. Interferon (IFN)-γ acts as a negative regulator on the IL-4- and IL-13-induced eotaxin-3 expression via STAT-1 activation. Eotaxin-3 expression was elevated specifically in the active lesions of IBD, in particular UC. Eotaxin-3 derived from colonic myofibroblasts may play an important role in the pathophysiology of UC. PMID:23607908

  19. Food-grade bacteria expressing elafin protect against inflammation and restore colon homeostasis.

    PubMed

    Motta, Jean-Paul; Bermúdez-Humarán, Luis G; Deraison, Céline; Martin, Laurence; Rolland, Corinne; Rousset, Perrine; Boue, Jérôme; Dietrich, Gilles; Chapman, Kevin; Kharrat, Pascale; Vinel, Jean-Pierre; Alric, Laurent; Mas, Emmanuel; Sallenave, Jean-Michel; Langella, Philippe; Vergnolle, Nathalie

    2012-10-31

    Elafin, a natural protease inhibitor expressed in healthy intestinal mucosa, has pleiotropic anti-inflammatory properties in vitro and in animal models. We found that mucosal expression of Elafin is diminished in patients with inflammatory bowel disease (IBD). This defect is associated with increased elastolytic activity (elastase-like proteolysis) in colon tissue. We engineered two food-grade strains of lactic acid bacteria (LAB) to express and deliver Elafin to the site of inflammation in the colon to assess the potential therapeutic benefits of the Elafin-expressing LAB. In mouse models of acute and chronic colitis, oral administration of Elafin-expressing LAB decreased elastolytic activity and inflammation and restored intestinal homeostasis. Furthermore, when cultures of human intestinal epithelial cells were treated with LAB secreting Elafin, the inflamed epithelium was protected from increased intestinal permeability and from the release of cytokines and chemokines, both of which are characteristic of intestinal dysfunction associated with IBD. Together, these results suggest that oral delivery of LAB secreting Elafin may be useful for treating IBD in humans. PMID:23115353

  20. Plasticity of enteric nerve functions in the inflamed and post-inflamed gut

    PubMed Central

    Mawe, Gary M.; Strong, Derek S.; Sharkey, Keith A.

    2009-01-01

    Inflammation of the gut alters the properties of the intrinsic and extrinsic neurons that innervate it. While the mechanisms of neuroplasticity differ amongst the inflammatory models that have been used, amongst various regions of the gut, and between intrinsic versus extrinsic neurons, a number of consistent features have been observed. For example, intrinsic and extrinsic primary afferent neurons become hyperexcitable in response to inflammation, and interneuronal synaptic transmission is facilitated in the enteric circuitry. These changes contribute to alterations in gut function and sensation in the inflamed bowel as well as functional disorders, and these changes persist for weeks beyond the point at which detectable inflammation has subsided. Thus, gaining a more thorough understanding of the mechanisms responsible for inflammation-induced neuroplasticity, and strategies to reverse these changes are clinically relevant goals. The purpose of this review is to summarize our current knowledge regarding neurophysiological changes that occur during and following intestinal inflammation, and to identify and address gaps in our knowledge regarding the role of enteric neuroplasticity in inflammatory and functional gastrointestinal disorders. PMID:19368664

  1. Biomechanics of oral mucosa

    PubMed Central

    Chen, Junning; Ahmad, Rohana; Li, Wei; Swain, Michael; Li, Qing

    2015-01-01

    The prevalence of prosthodontic treatment has been well recognized, and the need is continuously increasing with the ageing population. While the oral mucosa plays a critical role in the treatment outcome, the associated biomechanics is not yet fully understood. Using the literature available, this paper provides a critical review on four aspects of mucosal biomechanics, including static, dynamic, volumetric and interactive responses, which are interpreted by its elasticity, viscosity/permeability, apparent Poisson's ratio and friction coefficient, respectively. Both empirical studies and numerical models are analysed and compared to gain anatomical and physiological insights. Furthermore, the clinical applications of such biomechanical knowledge on the mucosa are explored to address some critical concerns, including stimuli for tissue remodelling (interstitial hydrostatic pressure), pressure–pain thresholds, tissue displaceability and residual bone resorption. Through this review, the state of the art in mucosal biomechanics and their clinical implications are discussed for future research interests, including clinical applications, computational modelling, design optimization and prosthetic fabrication. PMID:26224566

  2. Biomechanics of oral mucosa.

    PubMed

    Chen, Junning; Ahmad, Rohana; Li, Wei; Swain, Michael; Li, Qing

    2015-08-01

    The prevalence of prosthodontic treatment has been well recognized, and the need is continuously increasing with the ageing population. While the oral mucosa plays a critical role in the treatment outcome, the associated biomechanics is not yet fully understood. Using the literature available, this paper provides a critical review on four aspects of mucosal biomechanics, including static, dynamic, volumetric and interactive responses, which are interpreted by its elasticity, viscosity/permeability, apparent Poisson's ratio and friction coefficient, respectively. Both empirical studies and numerical models are analysed and compared to gain anatomical and physiological insights. Furthermore, the clinical applications of such biomechanical knowledge on the mucosa are explored to address some critical concerns, including stimuli for tissue remodelling (interstitial hydrostatic pressure), pressure-pain thresholds, tissue displaceability and residual bone resorption. Through this review, the state of the art in mucosal biomechanics and their clinical implications are discussed for future research interests, including clinical applications, computational modelling, design optimization and prosthetic fabrication. PMID:26224566

  3. Colonic Polyps

    MedlinePlus

    ... Colonic polyps grow in the large intestine, or colon. Most polyps are not dangerous. However, some polyps ... member with polyps Have a family history of colon cancer Most colon polyps do not cause symptoms. ...

  4. Enhanced visualization of oral cavity for early inflamed tissue detection.

    PubMed

    Wang, Hsiang-Chen; Chen, Yung-Tsan; Lin, Jui-Teng; Chiang, Chun-Ping; Cheng, Fang-Hsuan

    2010-05-24

    We describe a color image reconstruction method that enables both direct visualization and direct digital image acquisition from one oral tissue by using various light sources and color compensating filters. In this method, the image of the oral tissue with white light emitting diodes (LEDs) with blue color compensating filter has a larger color difference between the normal and inflamed tissues. The enhanced visualization comes from the white light color mixing between the red normal tissue and bluish white light from the LEDs. With our method, we evaluate the perceived tissue reflectance in each pixel of the image and color reproduction with different illuminated spectra. Our approach to enhancement of visually perceived color difference between normal and inflamed oral tissue involves optimization of illumination and observation conditions by allowing a significant optical contrast of illuminated spectrum to reach the observer's eyes. In comparison with a conventional daylight LED flashlight, a LED with blue filter as the illuminant for oral cavity detection enhances the color difference between normal and inflamed tissues by 32%. PMID:20589041

  5. [Physiological role of mucins in the colonic barrier integrity].

    PubMed

    Gaudier, Estelle; Hoebler, Christine

    2006-01-01

    Colonic mucus is a key element of colonic barrier as it is located at the frontier between luminal microflora and colonic mucosa itself. Colonic mucus is mainly composed of high molecular weight glycoproteins called mucins that can be either secreted or membrane-linked. The expression of various colonic mucins is altered in colorectal cancers or inflammations. The aim of this review is to highlight the crucial role played by colonic mucins in the maintenance of colonic barrier integrity, both because they are part of the protective mucus layer, and because they individually exert specific functions involved in epithelial barrier, like cell growth and differentiation, immunomodulation, signal transduction or cell adhesion. PMID:17075443

  6. Non-cell autonomous effects of targeting inducible PGE2 synthesis during inflammation-associated colon carcinogenesis

    PubMed Central

    Nakanishi, Masako; Perret, Christine; Meuillet, Emmanuelle J.; Rosenberg, Daniel W.

    2015-01-01

    Microsomal PGE2 synthase-1 (mPGES-1), the terminal enzyme in the formation of inducible PGE2, represents a potential target for cancer chemoprevention. We have previously shown that genetic abrogation of mPGES-1 significantly suppresses tumorigenesis in two preclinical models of intestinal cancer. In this study, we examined the role of mPGES-1 during colon tumorigenesis in the presence of dextran sulfate sodium (DSS)-induced inflammatory microenvironment. Using Apc Δ14/+ in which the mPGES-1 gene is either wild-type (D14:WT) or deleted (D14:KO), we report that mPGES-1 deficiency enhances sensitivity to acute mucosal injury. As a result of the increased epithelial damage, protection against adenoma formation is unexpectedly compromised in the D14:KO mice. Examining the DSS-induced acute injury, cryptal structures are formed within inflamed areas of colonic mucosa of both genotypes that display the hallmarks of early neoplasia. When acute epithelial injury is balanced by titration of DSS exposures, however, these small cryptal lesions progress rapidly to adenomas in the D14:WT mice. Given that mPGES-1 is highly expressed within the intestinal stroma under the inflammatory conditions of DSS-induced ulceration, we propose a complex and dual role for inducible PGE2 synthesis within the colonic mucosa. Our data suggest that inducible PGE2 is critical for the maintenance of an intact colonic epithelial barrier, while promoting epithelial regeneration. This function is exploited during neoplastic transformation in Apc Δ14/+ mice as PGE2 contributes to the growth and expansion of the early initiated cryptal structures. Taken together, inducible PGE2 plays a complex role in inflammation-associated cancers that requires further analysis. Inducible PGE2 production by mPGES-1 is critical for the colonic mucosal homeostasis. This function is exploited in the presence of the neoplastic transformation in Apc Δ14/+ mice as PGE2 contributes to the growth and expansion of the

  7. Non-cell autonomous effects of targeting inducible PGE2 synthesis during inflammation-associated colon carcinogenesis.

    PubMed

    Nakanishi, Masako; Perret, Christine; Meuillet, Emmanuelle J; Rosenberg, Daniel W

    2015-04-01

    Microsomal PGE2 synthase-1 (mPGES-1), the terminal enzyme in the formation of inducible PGE2, represents a potential target for cancer chemoprevention. We have previously shown that genetic abrogation of mPGES-1 significantly suppresses tumorigenesis in two preclinical models of intestinal cancer. In this study, we examined the role of mPGES-1 during colon tumorigenesis in the presence of dextran sulfate sodium (DSS)-induced inflammatory microenvironment. Using Apc (Δ14/+) in which the mPGES-1 gene is either wild-type (D14:WT) or deleted (D14:KO), we report that mPGES-1 deficiency enhances sensitivity to acute mucosal injury. As a result of the increased epithelial damage, protection against adenoma formation is unexpectedly compromised in the D14:KO mice. Examining the DSS-induced acute injury, cryptal structures are formed within inflamed areas of colonic mucosa of both genotypes that display the hallmarks of early neoplasia. When acute epithelial injury is balanced by titration of DSS exposures, however, these small cryptal lesions progress rapidly to adenomas in the D14:WT mice. Given that mPGES-1 is highly expressed within the intestinal stroma under the inflammatory conditions of DSS-induced ulceration, we propose a complex and dual role for inducible PGE2 synthesis within the colonic mucosa. Our data suggest that inducible PGE2 is critical for the maintenance of an intact colonic epithelial barrier, while promoting epithelial regeneration. This function is exploited during neoplastic transformation in Apc (Δ14/+) mice as PGE2 contributes to the growth and expansion of the early initiated cryptal structures. Taken together, inducible PGE2 plays a complex role in inflammation-associated cancers that requires further analysis. Inducible PGE2 production by mPGES-1 is critical for the colonic mucosal homeostasis. This function is exploited in the presence of the neoplastic transformation in Apc (Δ14/+) mice as PGE2 contributes to the growth and expansion of

  8. Colon cancer

    MedlinePlus

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma ... In the United States, colorectal cancer is one of the leading causes of deaths due to cancer. Early diagnosis can often lead to a complete cure. Almost ...

  9. Raman spectroscopy of endoscopic colonic biopsies from patients with ulcerative colitis to identify mucosal inflammation and healing

    PubMed Central

    Addis, James; Mohammed, Noor; Rotimi, Olorunda; Magee, Derek; Jha, Animesh; Subramanian, Venkataraman

    2016-01-01

    Raman spectroscopy was used to differentiate between mucosally healed (or quiescent) and inflamed colon tissue, as assessed endoscopically, in patients with ulcerative colitis. From the analysis of the Raman spectra of 60 biopsy tissue samples, clear differences were identified between the spectra of the quiescent and inflamed tissue. Three carotenoid peaks were found to be approximately twice as intense in the inflamed tissue. Two phospholipid peaks were found to be significantly lower in the inflamed tissue. Using multivariate statistical analysis, we show that these five peaks can be used to discriminate between endoscopically quiescent and inflamed tissue. We also correlated the Raman data with a histological assessment of the tissue. Four of the five peaks were found to be significantly different between the spectra of histologically healed (or quiescent) and histologically inflamed tissue. These findings indicate the ability of Raman spectroscopy to accurately classify colon tissue as either quiescent or inflamed, irrespective of whether an endoscopic or histological grading scheme is followed. We thus demonstrate that Raman spectroscopy could potentially be used as an early diagnosis tool for assessing the presence of mucosal healing or inflammation in patients with ulcerative colitis. PMID:27231640

  10. Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease.

    PubMed Central

    Oberg, S; Peters, J H; DeMeester, T R; Chandrasoma, P; Hagen, J A; Ireland, A P; Ritter, M P; Mason, R J; Crookes, P; Bremner, C G

    1997-01-01

    OBJECTIVE: The purpose of the study was to test the hypothesis that cardiac mucosa, carditis, and specialized intestinal metaplasia at an endoscopically normal-appearing cardia are manifestations of gastroesophageal reflux disease. SUMMARY BACKGROUND DATA: In the absence of esophageal mucosal injury, the diagnosis of gastroesophageal reflux disease currently rests on 24-hour pH monitoring. Histologic examination of the esophagus is not useful. The recent identification of specialized intestinal metaplasia at the cardia, along with the observation that it occurs in inflamed cardiac mucosa, led the authors to focus on the type and condition of the mucosa at the gastroesophageal junction and its relation to gastroesophageal reflux disease. METHODS: Three hundred thirty-four consecutive patients with symptoms of foregut disease, no evidence of columnar-lined esophagus, and no history of gastric or esophageal surgery were evaluated by 1) endoscopic biopsies above, at, and below the gastroesophageal junction; 2) esophageal motility; and 3) 24-hour esophageal pH monitoring. The patients were divided into groups depending on the histologic presence of cardiac epithelium with and without inflammation or associated intestinal metaplasia. Markers of gastroesophageal reflux disease were compared between groups (i.e., lower esophageal sphincter characteristics, esophageal acid exposure, the presence of endoscopic erosive esophagitis, and hiatal hernia). RESULTS: When cardiac epithelium was found, it was inflamed in 96% of the patients. The presence of cardiac epithelium and carditis was associated with deterioration of lower esophageal sphincter characteristics and increased esophageal acid exposure. Esophagitis occurred more commonly in patients with carditis whose sphincter, on manometry, was structurally defective. Specialized intestinal metaplasia at the cardia was only seen in inflamed cardiac mucosa, and its prevalence increased both with increasing acid exposure and with

  11. Loss of EP2 receptor subtype in colonic cells compromise epithelial barrier integrity by altering claudin-4.

    PubMed

    Lejeune, Manigandan; Moreau, France; Chadee, Kris

    2014-01-01

    Prostaglandin E2 (PGE2) is a bioactive lipid mediator that exerts its biological function through interaction with four different subtypes of E-Prostanoid receptor namely EP1, EP2, EP3 and EP4. It has been known that EP2 receptor is differentially over-expressed in the epithelia of inflamed human colonic mucosa. However, the significance of the differential expression in altering epithelial barrier function is not known. In this study, we used Caco-2 cells expressing EP2 receptor, either high (EP2S) or low (EP2A), as a model epithelia and determined the barrier function of these cell monolayers by measuring the trans epithelial resistance (TER). Basal TER of EP2A (but not EP2S) monolayer was significantly lower suggesting a loss of colonic epithelial barrier integrity. In comparison, the TER of wild type Caco-2 was decreased in response to an EP2 receptor specific antagonist (AH-6809) indicating an important role for EP2 receptor in the maintenance of epithelial barrier function. The decrease TER in EP2A monolayer corresponded with a significant loss of the tight junction (TJ) protein claudin-4 without affecting other major TJ proteins. Similarly, EP2 receptor antagonism/siRNA based silencing significantly decreased claudin-4 expression in EP2S cells. Surprisingly, alteration in claudin-4 was not transcriptionally regulated in EP2A cells but rather undergoes increased proteosomal degradation. Moreover, among the TER compromising cytokines examined (IL-8, IL-1β, TNF-α, IFN-γ) only IFN-γ was significantly up regulated in EP2A cells. However, IFN-γ did not significantly decreased claudin-4 expression in Caco-2 cells indicating no role for IFN-γ in degrading claudin-4. We conclude that differential down-regulation of EP2 receptor play a major role in compromising colonic epithelial barrier function by selectively increasing proteosomal degradation of claudin-4. PMID:25396731

  12. Colon-targeted delivery of piceatannol enhances anti-colitic effects of the natural product: potential molecular mechanisms for therapeutic enhancement

    PubMed Central

    Yum, Soohwan; Jeong, Seongkeun; Lee, Sunyoung; Nam, Joon; Kim, Wooseong; Yoo, Jin-Wook; Kim, Min-Soo; Lee, Bok Luel; Jung, Yunjin

    2015-01-01

    Piceatannol (PCT), an anti-colitic natural product, undergoes extensive Phase II hepatic metabolism, resulting in very low bioavailability. We investigated whether colon-targeted delivery of PCT could enhance anti-colitic effects and how therapeutic enhancement occurred at the molecular level. Molecular effects of PCT were examined in human colon carcinoma cells and inflamed colons. The anti-colitic effects of PCT in a colon-targeted capsule (colon-targeted PCT) were compared with PCT in a gelatin capsule (conventional PCT) in a trinitrobenzene sulfonic acid-induced rat colitis model. Colon-targeted PCT elicited greatly enhanced recovery of the colonic inflammation. In HCT116 cells, PCT inhibited nuclear factor kappaB while activating anti-colitic transcription factors, nuclear factor-erythroid 2 (NF-E2) p45-related factor 2, and hypoxia-inducible factor-1. Colon-targeted PCT, but not conventional PCT, modulated production of the target gene products of the transcription factors in the inflamed colonic tissues. Rectal administration of PCT, which simulates the therapeutic action of colon-targeted PCT, also ameliorated rat colitis and reproduced the molecular effects in the inflamed colonic tissues. Colon-targeted delivery increased therapeutic efficacy of PCT against colitis, likely resulting from multitargeted effects exerted by colon-targeted PCT. The drug delivery technique may be useful for therapeutic optimization of anti-colitic lead compounds including natural products. PMID:26273188

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  15. Mesenchymal stem cells induce epithelial proliferation within the inflamed stomach.

    PubMed

    Donnelly, Jessica M; Engevik, Amy; Feng, Rui; Xiao, Chang; Boivin, Gregory P; Li, Jing; Houghton, JeanMarie; Zavros, Yana

    2014-06-15

    Bone marrow-derived mesenchymal stem cells (MSCs) sustain cancer cells by creating a microenvironment favorable for tumor growth. In particular, MSCs have been implicated in gastric cancer development. There is extensive evidence suggesting that Hedgehog signaling regulates tumor growth. However, very little is known regarding the precise roles of Hedgehog signaling and MSCs in tumor development within the stomach. The current study tests that hypothesis that Sonic Hedgehog (Shh), secreted from MSCs, provides a proliferative stimulus for the gastric epithelium in the presence of inflammation. Red fluorescent protein-expressing MSCs transformed in vitro (stMSCs) were transduced with lentiviral constructs containing a vector control (stMSC(vect)) or short hairpin RNA (shRNA) targeting the Shh gene (stMSC(ShhKO)). Gastric submucosal transplantation of wild-type MSCs (wtMSCs), wild-type MSCs overexpressing Shh (wtMSC(Shh)), stMSC(vect), or stMSC(ShhKO) cells in C57BL/6 control (BL/6) or gastrin-deficient (GKO) mice was performed and mice analyzed 30 and 60 days posttransplantation. Compared with BL/6 mice transplanted with wtMSC(Shh) and stMSC(vect) cells, inflamed GKO mice developed aggressive gastric tumors. Tumor development was not observed in mouse stomachs transplanted with wtMSC or stMSC(ShhKO) cells. Compared with stMSC(ShhKO)-transplanted mice, within the inflamed GKO mouse stomach, Shh-expressing stMSC(vect)- and wtMSC(Shh)-induced proliferation of CD44-positive cells. CD44-positive cells clustered in gland-like structures within the tumor stroma and were positive for Patched (Ptch) expression. We conclude that Shh, secreted from MSCs, provides a proliferative stimulus for the gastric epithelium that is associated with tumor development, a response that is sustained by chronic inflammation. PMID:24789207

  16. Colonic interposition: radiographic evaluation.

    PubMed

    Agha, F P; Orringer, M B

    1984-04-01

    This report reviews the clinical and radiographic features of 40 patients who underwent visceral esophageal substitution with colon for benign or malignant lesions of the esophagus. The incidence and radiographic identification of complications are discussed. All patients were routinely examined with barium esophagrams on postoperative day 10. If an anastomotic leak was suspected clinically before this time, studies were performed using water-soluble iodinated contrast material. Follow-up barium esophagrams were obtained 1-96 months after operation (average, 60 months) in 24 patients. Eight patients (21%) demonstrated asymptomatic "jejunization" of the colonic mucosa with no attributable clinical manifestations; this finding resolved in 1-3 months, without sequelae, and has not been reported before. The spectrum of ischemic changes in the colonic segment included mucosal edema, spasm, ulceration, loss of haustration, and frank necrosis. Radiographically detectable early postoperative complications included anastomotic leak in six (three pharyngocolic, three cervical esophagocolic) and aspiration of barium into the tracheobronchial tree due to incoordinated swallowing in eight. Late postoperative complications included anastomotic narrowing (12) malfunctioning of the colon due to impaired emptying (five), recurrent aspiration pneumonia (three), small bowel obstruction (three), transhiatal herniation of small bowel through the diaphragmatic hiatus (one), and reflux into the retained bypassed esophagus (one). PMID:6608225

  17. Scientific Results from the FIRST Instrument Deployment to Cerro Toco, Chile and from the Flight of the INFLAME Instrument

    NASA Technical Reports Server (NTRS)

    Mlynczak, Martin G.; Cageao, Richard P.; Johnson, David G.

    2011-01-01

    Results from the FIRST and INFLAME infrared Fourier Transform Spectrometers are presented. These are comprehensive measurements of the far-IR spectrum (FIRST) and the net infrared fluxes within the atmosphere (INFLAME).

  18. Vermilion Reconstruction with Genital Mucosa

    PubMed Central

    Weyandt, Gerhard H.; Woeckel, Achim; Kübler, Alexander C.

    2016-01-01

    Summary: Functional and aesthetical reconstruction, especially of the upper lip after ablative tumor surgery, can be very challenging. The skin of the lip might be sufficiently reconstructed by transpositional flaps from the nasolabial or facial area. Large defects of the lip mucosa, including the vestibule, are even more challenging due to the fact that flaps from the inner lining of the oral cavity often lead to functional impairments. We present a case of multiple vermilion and skin resections of the upper lip. At the last step, we had to resect even the whole vermilion mucosa, including parts of the oral mucosa of the vestibule, leaving a bare orbicularis oris muscle. To reconstruct the mucosal layer, we used a mucosal graft from the labia minora and placed it on the compromised lip and the former transpositional flaps for the reconstructed skin of the upper lip with very good functional and aesthetic results.

  19. Vermilion Reconstruction with Genital Mucosa.

    PubMed

    Müller-Richter, Urs D A; Weyandt, Gerhard H; Woeckel, Achim; Kübler, Alexander C

    2016-05-01

    Functional and aesthetical reconstruction, especially of the upper lip after ablative tumor surgery, can be very challenging. The skin of the lip might be sufficiently reconstructed by transpositional flaps from the nasolabial or facial area. Large defects of the lip mucosa, including the vestibule, are even more challenging due to the fact that flaps from the inner lining of the oral cavity often lead to functional impairments. We present a case of multiple vermilion and skin resections of the upper lip. At the last step, we had to resect even the whole vermilion mucosa, including parts of the oral mucosa of the vestibule, leaving a bare orbicularis oris muscle. To reconstruct the mucosal layer, we used a mucosal graft from the labia minora and placed it on the compromised lip and the former transpositional flaps for the reconstructed skin of the upper lip with very good functional and aesthetic results. PMID:27579226

  20. Confocal laser endomicroscopy to monitor the colonic mucosa of mice.

    PubMed

    Mielke, Lisa; Preaudet, Adele; Belz, Gabrielle; Putoczki, Tracy

    2015-06-01

    The gastrointestinal tract is a unique organ system that provides an epithelial barrier between our underlying immune system and luminal pathogens. Disruption of gastrointestinal homeostasis, as a result of impaired barrier function, is associated with numerous pathologies including inflammatory bowel disease and colorectal cancer. In parallel to the clinical development of endoscopy technologies to monitor and diagnose these pathologies in humans, advanced mouse colonoscopy techniques are being developed. When these technologies are coupled with model systems of human disease, which are essential to our understanding of the pathophysiology of gastrointestinal diseases, the requirement for euthanasia of multiple cohorts of mice is eliminated. Here we highlight the suitability of white light endoscopy to monitor the progression of colitis in mice. We further outline the experimental power of combined standard endoscopy with confocal microendoscopy, which permits visualization of fluorescent markers in a single animal in real-time. Together, these technologies will enhance our understanding of the interplay between components of the gastrointestinal microenvironment and their role in disease. PMID:25960174

  1. Laparoscopy as a Diagnostic and Definitive Therapeutic Tool in Cases of Inflamed Simple Lymphatic Cysts of the Mesentery

    PubMed Central

    Abdelaal, Abdelrahman; Sulieman, Ibnouf; Aftab, Zia; Ahmed, Ayman; Al-Mudares, Saif; Al Tarakji, Mohannad; Almuzrakchi, Ahmad; Di Carlo, Isidoro

    2015-01-01

    Mesenteric cysts are rare benign abdominal tumors. These cysts, especially those of lymphatic origin, very rarely become inflamed. The diagnosis of inflamed lymphatic cysts of the mesentery may be difficult. We herein report two cases of inflamed simple lymphatic cysts of the mesentery definitively diagnosed and excised by laparoscopy. PMID:26064760

  2. Immune/Inflammatory Response and Hypocontractility of Rabbit Colonic Smooth Muscle After TNBS-Induced Colitis

    PubMed Central

    Zhang, Yonggang; Li, Fang; Wang, Hong; Yin, Chaoran; Huang, JieAn; Mahavadi, Sunila; Murthy, Karnam S.

    2016-01-01

    Background The contractility of colonic smooth muscle is dysregulated due to immune/inflammatory responses in inflammatory bowel diseases. Inflammation in vitro induces up-regulation of regulator of G-protein signaling 4 (RGS4) expression in colonic smooth muscle cells. Aims To characterize the immune/inflammatory responses and RGS4 expression pattern in colonic smooth muscle after induction of colitis. Methods Colitis was induced in rabbits by intrarectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Innate/adaptive immune response RT-qPCR array was performed using colonic circular muscle strips. At 1–9 weeks after colonic intramuscular microinjection of lentivirus, the distal and proximal colons were collected, and muscle strips and dispersed muscle cells were prepared from circular muscle layer. Expression levels of RGS4 and NFκB signaling components were determined by Western blot analysis. The biological consequences of RGS4 knockdown were assessed by measurement of muscle contraction and phospholipase C (PLC)-β activity in response to acetylcholine (ACh). Results Contraction in response to ACh was significantly inhibited in the inflamed colonic circular smooth muscle cells. RGS4, IL-1, IL-6, IL-8, CCL3, CD1D, and ITGB2 were significantly up-regulated, while IL-18, CXCR4, CD86, and C3 were significantly down-regulated in the inflamed muscle strips. RGS4 protein expression in the inflamed smooth muscles was dramatically increased. RGS4 stable knockdown in vivo augmented ACh-stimulated PLC-β activity and contraction in colonic smooth muscle cells. Conclusion Inflamed smooth muscle exhibits up-regulation of IL-1-related signaling components, Th1 cytokines and RGS4, and inhibition of contraction. Stable knockdown of endogenous RGS4 in colonic smooth muscle increases PLC-β activity and contractile responses. PMID:26879904

  3. Computed tomography identification of an exophytic colonic liposarcoma.

    PubMed

    Chou, Chung Kuao; Chen, Sung-Ting

    2016-09-01

    It may be difficult to ascertain the relationship between a large intra-abdominal tumor and the adjacent organs if they are close together. In the current case, a definitive preoperative diagnosis of an exophytic colonic tumor was obtained by the demonstration of obtuse angles between the tumor and colon and by distinct recognition of the mucosa-submucosa of the colonic wall on computed tomography; the accuracy of this preoperative diagnosis was subsequently confirmed by pathologic findings. PMID:27594941

  4. The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa

    PubMed Central

    Saban, Marcia R; Hellmich, Helen L; Turner, Mary; Nguyen, Ngoc-Bich; Vadigepalli, Rajanikanth; Dyer, David W; Hurst, Robert E; Centola, Michael; Saban, Ricardo

    2006-01-01

    Background An organ such as the bladder consists of complex, interacting set of tissues and cells. Inflammation has been implicated in every major disease of the bladder, including cancer, interstitial cystitis, and infection. However, scanty is the information about individual detrusor and urothelium transcriptomes in response to inflammation. Here, we used suppression subtractive hybridizations (SSH) to determine bladder tissue- and disease-specific genes and transcriptional regulatory elements (TRE)s. Unique TREs and genes were assembled into putative networks. Results It was found that the control bladder mucosa presented regulatory elements driving genes such as myosin light chain phosphatase and calponin 1 that influence the smooth muscle phenotype. In the control detrusor network the Pax-3 TRE was significantly over-represented. During development, the Pax-3 transcription factor (TF) maintains progenitor cells in an undifferentiated state whereas, during inflammation, Pax-3 was suppressed and genes involved in neuronal development (synapsin I) were up-regulated. Therefore, during inflammation, an increased maturation of neural progenitor cells in the muscle may underlie detrusor instability. NF-κB was specifically over-represented in the inflamed mucosa regulatory network. When the inflamed detrusor was compared to control, two major pathways were found, one encoding synapsin I, a neuron-specific phosphoprotein, and the other an important apoptotic protein, siva. In response to LPS-induced inflammation, the liver X receptor was over-represented in both mucosa and detrusor regulatory networks confirming a role for this nuclear receptor in LPS-induced gene expression. Conclusion A new approach for understanding bladder muscle-urothelium interaction was developed by assembling SSH, real time PCR, and TRE analysis results into regulatory networks. Interestingly, some of the TREs and their downstream transcripts originally involved in organogenesis and

  5. Modulation of adult-born neurons in the inflamed hippocampus

    PubMed Central

    Belarbi, Karim; Rosi, Susanna

    2013-01-01

    Throughout life new neurons are continuously added to the hippocampal circuitry involved with spatial learning and memory. These new cells originate from neural precursors in the subgranular zone of the dentate gyrus, migrate into the granule cell layer, and integrate into neural networks encoding spatial and contextual information. This process can be influenced by several environmental and endogenous factors and is modified in different animal models of neurological disorders. Neuroinflammation, as defined by the presence of activated microglia, is a common key factor to the progression of neurological disorders. Analysis of the literature shows that microglial activation impacts not only the production, but also the migration and the recruitment of new neurons. The impact of microglia on adult-born neurons appears much more multifaceted than ever envisioned before, combining both supportive and detrimental effects that are dependent upon the activation phenotype and the factors being released. The development of strategies aimed to change microglia toward states that promote functional neurogenesis could therefore offer novel therapeutic opportunities against neurological disorders associated with cognitive deficits and neuroinflammation. The present review summarizes the current knowledge on how production, distribution, and recruitment of new neurons into behaviorally relevant neural networks are modified in the inflamed hippocampus. PMID:24046730

  6. Modulation of Leukocyte Behavior by an Inflamed Extracellular Matrix

    PubMed Central

    Schor, Hagai; Vaday, Gayle G.

    2000-01-01

    Inflammation is a response of the immune system to foreign insult or physical damage. Various cellular and humoral components of the immune system are recruited from the vascular system and are translocated through endothelium, and into extracellular matrix (ECM) compartments of inflamed tissues. This translocation is orchestrated by various types of accessory signals, in the form of soluble or complexed molecules, which evoke remarkable transitions in leukocyte activities. Recruited inflammatory cells give rise to mechanisms of migration, including the secretion of enzymes and other pro-inflammatory mediators and the alteration of their adhesive contacts with the ECM. Hence, migrating cells secrete enzymes, chemokines, and cytokines which interact with the ECM, and thereby, provide the cells with intrinsic signals for coordinating their responses. Resultant products of enzymatic modifications to the ECM microenvironment, such as cytokine- and ECM-derived molecules, may be also part of a cell-signaling mechanism that provides leukocytes with information about the nature of their inflammatory activity; such a mechanism may give the immune system data that can be cognitively interpreted for consequential activities. This article reviews the findings that support this notion and describe the dynamic interactions between participants of the inflammatory processes. PMID:11097214

  7. CRK proteins selectively regulate T cell migration into inflamed tissues

    PubMed Central

    Huang, Yanping; Clarke, Fiona; Karimi, Mobin; Roy, Nathan H.; Williamson, Edward K.; Okumura, Mariko; Mochizuki, Kazuhiro; Chen, Emily J.H.; Park, Tae-Ju; Debes, Gudrun F.; Zhang, Yi; Curran, Tom; Kambayashi, Taku; Burkhardt, Janis K.

    2015-01-01

    Effector T cell migration into inflamed sites greatly exacerbates tissue destruction and disease severity in inflammatory diseases, including graft-versus-host disease (GVHD). T cell migration into such sites depends heavily on regulated adhesion and migration, but the signaling pathways that coordinate these functions downstream of chemokine receptors are largely unknown. Using conditional knockout mice, we found that T cells lacking the adaptor proteins CRK and CRK-like (CRKL) exhibit reduced integrin-dependent adhesion, chemotaxis, and diapedesis. Moreover, these two closely related proteins exhibited substantial functional redundancy, as ectopic expression of either protein rescued defects in T cells lacking both CRK and CRKL. We determined that CRK proteins coordinate with the RAP guanine nucleotide exchange factor C3G and the adhesion docking molecule CASL to activate the integrin regulatory GTPase RAP1. CRK proteins were required for effector T cell trafficking into sites of inflammation, but not for migration to lymphoid organs. In a murine bone marrow transplantation model, the differential migration of CRK/CRKL-deficient T cells resulted in efficient graft-versus-leukemia responses with minimal GVHD. Together, the results from our studies show that CRK family proteins selectively regulate T cell adhesion and migration at effector sites and suggest that these proteins have potential as therapeutic targets for preventing GVHD. PMID:25621495

  8. Mechanisms of tumor escape in the context of the T-cell-inflamed and the non-T-cell-inflamed tumor microenvironment.

    PubMed

    Spranger, Stefani

    2016-08-01

    Checkpoint blockade therapy has been proven to be highly active across many cancer types but emerging evidence indicates that the therapeutic benefit is limited to a subset of patients in each cancer entity. The presence of CD8(+) T cells within the tumor microenvironment or the invasive margin of the tumor, as well as the up-regulation of PD-L1, have emerged to be the most predictive biomarkers for clinical benefit in response to checkpoint inhibition. Although the up-regulation of immune inhibitory mechanisms is one mechanism of immune escape, commonly used by T-cell-inflamed tumors, exclusion of an anti-tumor specific T-cell infiltrate displays another even more potent mechanism of immune escape. This review will contrast the mechanisms of immunogenic, T-cell-inflamed, and the novel concept of non-immunogenic, non-T-cell-inflamed, adaptive immune escape. PMID:26989092

  9. Giant colon lipoma

    PubMed Central

    Yaman, İsmail; Derici, Hayrullah; Demirpolat, Gülen

    2015-01-01

    Colon lipomas are rare, non-epithelial tumors. They are generally smaller than two centimeters and asymptomatic, they are incidentally diagnosed and do not require treatment. Large and symptomatic colon lipomas are rather rare. Its differential diagnosis is generally made by histopathological examination of the resected specimen. A fifty-year-old female patient presented with the symptoms of abdominal pain, swelling in the abdomen and loss of weight. During colonoscopy, there was a submucosal mass of 8×6 cm, which almost completely obstructed the lumen in the hepatic flexure and was covered by a mucosa that was sporadically ulcerated and necrotic in nature. In magnetic resonance imaging, an ovoid mass with a diameter of 8.5 cm at its widest dimension was detected, which had signal intensity similar to that of adipose tissue. Since the patient was symptomatic and differential diagnosis could not be made, she underwent laparoscopic right hemicolectomy. A submucosal lipoma was detected on histopathological examination of the specimen. The patient was discharged without any problems on post-operative day 7. Definite diagnosis of lipomas before surgery is challenging; they may be mistaken for malignancy, especially if the lesion is large and ulcerated. For large and symptomatic colon lipomas, surgery is required to both prevent complications and rule out malignancy. PMID:26170744

  10. Sigmoid volvulus after laparoscopic surgery for sigmoid colon cancer.

    PubMed

    Sadatomo, Ai; Miyakura, Yasuyuki; Zuiki, Toru; Koinuma, Koji; Horie, Hisanaga; Lefor, Alan T; Yasuda, Yoshikazu

    2013-08-01

    We report the first case of sigmoid volvulus after laparoscopic surgery for sigmoid colon cancer. The patient is a 75-year-old man who presented with the sudden onset of severe abdominal pain. He had undergone laparoscopic sigmoidectomy for cancer 2 years before presentation. CT scan showed a distended sigmoid colon with a mesenteric twist, or "whirl sign." Colonoscopy showed a mucosal spiral and luminal stenosis with dilated sigmoid colon distally and ischemic mucosa. The diagnosis of ischemic colonic necrosis due to sigmoid volvulus was established. Resection of the necrotic sigmoid colon was performed and a descending colon stoma was created. A long remnant sigmoid colon and chronic constipation may contribute to the development of sigmoid volvulus after laparoscopic sigmoidectomy. Prompt diagnosis is essential for adequate treatment, and colonoscopy aids in the diagnosis of ischemic changes in patients without definitive findings of a gangrenous colon. PMID:23879414

  11. Epstein-Barr Virus Infection in Chronically Inflamed Periapical Granulomas

    PubMed Central

    Makino, Kosuke; Takeichi, Osamu; Hatori, Keisuke; Imai, Kenichi; Ochiai, Kuniyasu; Ogiso, Bunnai

    2015-01-01

    Periapical granulomas are lesions around the apex of a tooth caused by a polymicrobial infection. Treatment with antibacterial agents is normally performed to eliminate bacteria from root canals; however, loss of the supporting alveolar bone is typically observed, and tooth extraction is often selected if root canal treatment does not work well. Therefore, bacteria and other microorganisms could be involved in this disease. To understand the pathogenesis of periapical granulomas more precisely, we focused on the association with Epstein-Barr virus (EBV) using surgically removed periapical granulomas (n = 32). EBV DNA was detected in 25 of 32 periapical granulomas (78.1%) by real-time PCR, and the median number of EBV DNA copies was approximately 8,688.01/μg total DNA. In contrast, EBV DNA was not detected in healthy gingival tissues (n = 10); the difference was statistically significant according to the Mann-Whitney U test (p = 0.0001). Paraffin sections were also analyzed by in situ hybridization to detect EBV-encoded small RNA (EBER)-expressing cells. EBER was detected in the cytoplasm and nuclei of B cells and plasma cells in six of nine periapical granulomas, but not in healthy gingival tissues. In addition, immunohistochemical analysis for latent membrane protein 1 (LMP-1) of EBV using serial tissue sections showed that LMP-1-expressing cells were localized to the same areas as EBER-expressing cells. These data suggest that B cells and plasma cells in inflamed granulomas are a major source of EBV infection, and that EBV could play a pivotal role in controlling immune cell responses in periapical granulomas. PMID:25884725

  12. Colonic microbiome is altered in alcoholism

    PubMed Central

    Mutlu, Ece A.; Gillevet, Patrick M.; Rangwala, Huzefa; Sikaroodi, Masoumeh; Naqvi, Ammar; Engen, Phillip A.; Kwasny, Mary; Lau, Cynthia K.

    2012-01-01

    Several studies indicate the importance of colonic microbiota in metabolic and inflammatory disorders and importance of diet on microbiota composition. The effects of alcohol, one of the prominent components of diet, on colonic bacterial composition is largely unknown. Mounting evidence suggests that gut-derived bacterial endotoxins are cofactors for alcohol-induced tissue injury and organ failure like alcoholic liver disease (ALD) that only occur in a subset of alcoholics. We hypothesized that chronic alcohol consumption results in alterations of the gut microbiome in a subgroup of alcoholics, and this may be responsible for the observed inflammatory state and endotoxemia in alcoholics. Thus we interrogated the mucosa-associated colonic microbiome in 48 alcoholics with and without ALD as well as 18 healthy subjects. Colonic biopsy samples from subjects were analyzed for microbiota composition using length heterogeneity PCR fingerprinting and multitag pyrosequencing. A subgroup of alcoholics have an altered colonic microbiome (dysbiosis). The alcoholics with dysbiosis had lower median abundances of Bacteroidetes and higher ones of Proteobacteria. The observed alterations appear to correlate with high levels of serum endotoxin in a subset of the samples. Network topology analysis indicated that alcohol use is correlated with decreased connectivity of the microbial network, and this alteration is seen even after an extended period of sobriety. We show that the colonic mucosa-associated bacterial microbiome is altered in a subset of alcoholics. The altered microbiota composition is persistent and correlates with endotoxemia in a subgroup of alcoholics. PMID:22241860

  13. Pigmented Lesion of Buccal Mucosa

    PubMed Central

    Bajpai, Manas; Kumar, Malay; Kumar, Manish; Agarwal, Deshant

    2014-01-01

    Pigmented lesions are commonly found in the mouth. Such lesions represent a variety of clinical entities, ranging from physiologic changes to manifestation of systemic illness and malignant neoplasm. Diagnosis of such lesions requires a proper case history, extraoral and intraoral examination, and, in some cases, biopsy, aspiration cytology, and laboratory investigations. Here we present a case of purple lesion on the buccal mucosa of a 34-year-old male patient which was provisionally diagnosed as mucocele but on the basis of histopathological picture it was finally diagnosed as angiofibroma, and we also discuss the clinical and histopathological differential diagnosis. PMID:25161669

  14. Pigmented lesion of buccal mucosa.

    PubMed

    Bajpai, Manas; Kumar, Malay; Kumar, Manish; Agarwal, Deshant

    2014-01-01

    Pigmented lesions are commonly found in the mouth. Such lesions represent a variety of clinical entities, ranging from physiologic changes to manifestation of systemic illness and malignant neoplasm. Diagnosis of such lesions requires a proper case history, extraoral and intraoral examination, and, in some cases, biopsy, aspiration cytology, and laboratory investigations. Here we present a case of purple lesion on the buccal mucosa of a 34-year-old male patient which was provisionally diagnosed as mucocele but on the basis of histopathological picture it was finally diagnosed as angiofibroma, and we also discuss the clinical and histopathological differential diagnosis. PMID:25161669

  15. INFLAME: In-situ net flux within the atmosphere of the Earth

    NASA Astrophysics Data System (ADS)

    Mlynczak, M. G.; Johnson, D. G.

    2006-12-01

    The In-situ Net FLux within the AtMosphere of the Earth (INFLAME) instrument is designed to make direct measurements of the net radiative flux within the Earth's atmosphere. Deployed on an uninhabited aerial vehicle (UAV) the INFLAME instruments will record vertical profiles of net radiative flux separately for the visible and infrared streams of radiation within the atmosphere. Upon differentiation of these vertical profiles the divergence of the net flux is obtained, which combined with the atmospheric density yields the rate of radiative heating (Kelvin per day) within the atmosphere. INFLAME offers the advantage of using a Fourier Transform Spectrometer (FTS) to directly measure the net flux, thereby avoiding potentially large errors in the derived heating rate associated with differencing separate measurements of the upwelling and downwelling fluxes of radiation. INFLAME is a new project in NASA's Instrument Incubator Program (IIP). We will describe the science motivating the measurements, the historical background to the measurements, and the INFLAME instrument now under development at the NASA Langley Research Center.

  16. Colon cancer

    MedlinePlus

    ... red or processed meats Have colorectal polyps Have inflammatory bowel disease ( Crohn disease or ulcerative colitis ) Have a family history of colon cancer Have a personal history of breast cancer Some inherited diseases also increase the risk ...

  17. Dysbiosis in the inflamed intestine: chance favors the prepared microbe.

    PubMed

    Winter, Sebastian E; Bäumler, Andreas J

    2014-01-01

    The bacterial microbiota of the human large bowel is a complex ecosystem consisting of several hundred, mostly anaerobic, species. To maintain colonization of the gut lumen and maximize growth in the presence of nutritional competitors, highly diverse metabolic pathways have evolved, with each microbe utilizing a different "winning strategy" for nutrient acquisition and utilization. Conditions and diseases leading to intestinal inflammation are accompanied by a severe disruption the microbiota composition characterized by an expansion of facultative anaerobic Enterobacteriaceae. Here, we review evidence that the local inflammatory response creates a unique nutritional environment that is conducive to a bloom of bacterial species whose genomes encode the capability of utilizing inflammation-derived nutrients. PMID:24637596

  18. Synaptic plasticity in myenteric neurons of the guinea-pig distal colon: presynaptic mechanisms of inflammation-induced synaptic facilitation

    PubMed Central

    Krauter, Eric M; Linden, David R; Sharkey, Keith A; Mawe, Gary M

    2007-01-01

    The purpose of this study was to investigate the pre- and postsynaptic mechanisms that contribute to synaptic facilitation in the myenteric plexus of the trinitrobenzene sulphonic acid-inflamed guinea-pig distal colon. Intracellular recordings of evoked fast excitatory postsynaptic potentials (fEPSPs) in myenteric S neurons were evaluated, and the density of synaptic terminals was morphometrically analysed by transmission electron microscopy. In inflamed tissue, fEPSPs were reduced to control levels by the protein kinase A (PKA) inhibitor, H89, but H89 did not affect the fEPSPs in control tissue. This PKA activation in inflamed tissue did not appear to involve 5-HT4 receptors because the antagonist/inverse agonist, GR 125487, caused comparable decreases of fEPSPs in both tissues. Inhibition of BK channels with iberiotoxin did not alter the fEPSPs in inflamed tissue, but increased the fEPSPs in control tissue to the amplitude detected in inflamed tissue. During trains of stimuli, run-down of EPSPs was less extensive in inflamed tissue and there was a significant increase in the paired pulse ratio. Depolarizations in response to exogenous neurotransmitters were not altered in inflamed tissue. These inflammation-induced changes were not accompanied by alterations in the pharmacological profile of EPSPs, and no changes in synaptic density were detected by electron microscopy. Collectively, these data indicate that synaptic facilitation in the inflamed myenteric plexus involves a presynaptic increase in PKA activity, possibly involving an inhibition of BK channels, and an increase in the readily releasable pool of synaptic vesicles. PMID:17363386

  19. STAT3 in Epithelial Cells Regulates Inflammation and Tumor Progression to Malignant State in Colon1

    PubMed Central

    Nguyen, Andrew V; Wu, Yuan-Yuan; Liu, Qiang; Wang, Donghai; Nguyen, Stephanie; Loh, Ricky; Pang, Joey; Friedman, Kenneth; Orlofsky, Amos; Augenlicht, Leonard; Pollard, Jeffrey W; Lin, Elaine Y

    2013-01-01

    Chronic inflammation is an important risk factor for the development of colorectal cancer; however, the mechanism of tumorigenesis especially tumor progression to malignancy in the inflamed colon is still unclear. Our study shows that epithelial signal transducer and activator of transcription 3 (STAT3), persistently activated in inflamed colon, is not required for inflammation-induced epithelial overproliferation and the development of early-stage tumors; however, it is essential for tumor progression to advanced malignancy. We found that one of the mechanisms that epithelial STAT3 regulates in tumor progression might be to modify leukocytic infiltration in the large intestine. Activation of epithelial STAT3 promotes the infiltration of the CD8+ lymphocyte population but inhibits the recruitment of regulatory T (Treg) lymphocytes. The loss of Stat3 in epithelial cells promoted the expression of cytokines/chemokines including CCL19, CCL28, and RANTES, which are known to be able to recruit Treg lymphocytes. Linked to these changes was the pathway mediated by sphingosine 1-phosphate receptor 1 and sphingosine 1-phosphate kinases, which is activated in colonic epithelial cells in inflamed colon with functional STAT3 but not in epithelial cells deleted of STAT3. Our data suggest that epithelial STAT3 plays a critical role in inflammation-induced tumor progression through regulation of leukocytic recruitment especially the infiltration of Treg cells in the large intestine. PMID:24027425

  20. Molecular Drivers of the Non-T-cell-Inflamed Tumor Microenvironment in Urothelial Bladder Cancer.

    PubMed

    Sweis, Randy F; Spranger, Stefani; Bao, Riyue; Paner, Gladell P; Stadler, Walter M; Steinberg, Gary; Gajewski, Thomas F

    2016-07-01

    Muscle-invasive urothelial bladder cancer is a common malignancy with poor outcomes for which immune checkpoint blockade is now showing promise. Despite clinical activity of PD-1/PD-L1-targeted therapy in this disease, most patients do not benefit and resistance mechanisms remain unknown. The non-T-cell-inflamed tumor microenvironment correlates with poor prognosis and resistance to immunotherapies. In this study, we determined tumor-oncogenic pathways correlating with T-cell exclusion. We first establish in this report that T-cell-inflamed bladder tumors can be identified by immune gene expression profiling with concordance with CD8(+) T-cell infiltration. Upregulation of genes encoding immune checkpoint proteins PD-L1, IDO, FOXP3, TIM3, and LAG3 was associated with T-cell-inflamed tumors, suggesting potential for sensitivity to checkpoint blockade. β-Catenin, PPAR-γ, and FGFR3 pathways were activated in non-T-cell-inflamed tumors. No difference was seen in overall somatic mutational density between groups. The three pathways identified represent targetable potential pathways of tumor-intrinsic immunotherapy resistance. Cancer Immunol Res; 4(7); 563-8. ©2016 AACR. PMID:27197067

  1. Autofluorescence of healthy and inflamed pulpal tissues: photodynamic diagnosis of pulpal tissue

    NASA Astrophysics Data System (ADS)

    Ebihara, Arata; Kawashima, Nobuyuki; Saegusa, Hidetoshi; Anjo, Tomoo; Suda, Hideaki

    2005-03-01

    Autofluorescence of healthy and inflamed human pulpal tissues was observed by confocal laser microscopy. In this preliminary study, photodynamic diagnosis (PDD) was applied to diagnose pulpal disease. The ability to accurately diagnose pulpal pathology prior to pulpectomy would be very beneficial. Clinically, however, we are unable to perform biopsy to detect pathological changes. Therefore, this study was performed using healthy, acutely and chronically inflamed human pulpal tissues to detect pathological changes in pulpal tissues. Following excision, pulpal tissues were rapidly frozen and standard cryosections were prepared. Autofluorescence of pulpal tissues was observed using a confocal laser microscope to examine whether there were any differences in autofluorescence intensities between healthy and inflamed pulpal tissues. Several combinations of excitation and detection wavelengths were tested to observe autofluorescence from pulpal tissues; the excitation wavelengths ranged from 488nm to 633nm, and the detection wavelengths were longer than 505 nm. Autofluorescence was detected in both healthy and inflamed groups. With this technique, it may be possible to diagnose pulpal pathology without biopsy, and might be applicable to photodynamic diagnosis (PDD) and photodynamic therapy (PDT) in root canal treatment.

  2. Matrix metalloproteinase levels and gelatinolytic activity in clinically healthy and inflamed human dental pulps.

    PubMed

    Gusman, Heloisa; Santana, Ronaldo B; Zehnder, Matthias

    2002-10-01

    The role of matrix metalloproteinases (MMPs) in the breakdown of pulp tissue of teeth with severe caries has not yet been directly elucidated. This study was to determine the levels of selected MMPs and the overall gelatinolytic activity in clinically healthy and inflamed human dental pulps of 29 healthy subjects, aged 10-19 yr. Seventeen pulps were collected from subjects diagnosed with symptomatic pulpitis, and 18 control pulps were obtained from 12 subjects following premolar extraction for orthodontic reasons. The levels of MMP-1, MMP-2, MMP-3 and MMP-9 were determined with enzyme-linked immunosorbent assay. Densitometric analysis of gelatin zymograms was used to assay gelatinolytic activity in pulp supernatants. The MMP-1 levels were below the detection limit for both groups. Levels of MMP-2 and MMP-3 were significantly lower in symptomatic vs. clinically healthy pulps. In contrast, levels of MMP-9 in inflamed pulps were significantly higher than those recorded in clinically normal pulps. The overall gelatinolytic activity was elevated in inflamed pulps compared with healthy counterparts. Further, the gelatinolytic activity was positively correlated with MMP-9 levels. The data obtained suggest a key role of MMP-9 in the breakdown of inflamed human dental pulp tissue. PMID:12664465

  3. Expression of corticotropin-releasing factor in inflamed tissue is required for intrinsic peripheral opioid analgesia.

    PubMed Central

    Schafer, M; Mousa, S A; Zhang, Q; Carter, L; Stein, C

    1996-01-01

    Immune cell-derived opioid peptides can activate opioid receptors on peripheral sensory nerves to inhibit inflammatory pain. The intrinsic mechanisms triggering this neuroimmune interaction are unknown. This study investigates the involvement of endogenous corticotropin-releasing factor (CRF) and interleukin-1beta (IL-1). A specific stress paradigm, cold water swim (CWS), produces potent opioid receptor-specific antinociception in inflamed paws of rats. This effect is dose-dependently attenuated by intraplantar but not by intravenous alpha-helical CRF. IL-1 receptor antagonist is ineffective. Similarly, local injection of antiserum against CRF, but not to IL-1, dose-dependently reverses this effect. Intravenous anti-CRF is only inhibitory at 10(4)-fold higher concentrations and intravenous CRF does not produce analgesia. Pretreatment of inflamed paws with an 18-mer 3'-3'-end inverted CRF-antisense oligodeoxynucleotide abolishes CWS-induced antinociception. The same treatment significantly reduces the amount of CRF extracted from inflamed paws and the number of CRF-immunostained cells without affecting gross inflammatory signs. A mismatch oligodeoxynucleotide alters neither the CWS effect nor CRF immunoreactivity. These findings identify locally expressed CRF as the predominant agent to trigger opioid release within inflamed tissue. Endogenous IL-1, circulating CRF or antiinflammatory effects, are not involved. Thus, an intact immune system plays an essential role in pain control, which is important for the understanding of pain in immunosuppressed patients with cancer or AIDS. Images Fig. 4 PMID:8650225

  4. Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-γt ubiquitination.

    PubMed

    Kathania, Mahesh; Khare, Prashant; Zeng, Minghui; Cantarel, Brandi; Zhang, Haiying; Ueno, Hideki; Venuprasad, K

    2016-08-01

    Dysregulated expression of interleukin 17 (IL-17) in the colonic mucosa is associated with colonic inflammation and cancer. However, the cell-intrinsic molecular mechanisms by which IL-17 expression is regulated remain unclear. We found that deficiency in the ubiquitin ligase Itch led to spontaneous colitis and increased susceptibility to colon cancer. Itch deficiency in the TH17 subset of helper T cells, innate lymphoid cells and γδ T cells resulted in the production of elevated amounts of IL-17 in the colonic mucosa. Mechanistically, Itch bound to the transcription factor ROR-γt and targeted ROR-γt for ubiquitination. Inhibition or genetic inactivation of ROR-γt attenuated IL-17 expression and reduced spontaneous colonic inflammation in Itch(-/-) mice. Thus, we have identified a previously unknown role for Itch in regulating IL-17-mediated colonic inflammation and carcinogenesis. PMID:27322655

  5. Gene Expression Pattern of Cells From Inflamed and Normal Areas of Osteoarthritis Synovial Membrane

    PubMed Central

    Lambert, Cécile; Dubuc, Jean-Emile; Montell, Eulàlia; Vergés, Josep; Munaut, Carine; Noël, Agnès; Henrotin, Yves

    2014-01-01

    Objective To compare the gene expression patterns of synovial cells from inflamed or normal/reactive areas of synovial membrane obtained from the same patient with osteoarthritis (OA). Methods At the time of total knee replacement, synovial tissues were obtained from 12 patients with knee OA. The inflammation status of the synovial membrane was characterized according to macroscopic criteria and classified as normal/reactive or inflamed. Biopsy samples were cultured separately for 7 days. Microarray gene expression profiling was performed on normal/reactive and inflamed areas. Western blot and immunohistochemistry were used to confirm the identified genes that were differentially expressed. Results We identified 896 genes that were differentially expressed between normal/reactive and inflamed areas. The key pathways were related to inflammation, cartilage metabolism, Wnt signaling, and angiogenesis. In the inflammation network, the genes TREM1 and S100A9 were strongly up-regulated. The genes MMP3, MMP9, CTSH (cathepsin H), and CTSS (cathepsin S) were significantly up-regulated in the cartilage catabolism pathway, while the most up-regulated anabolism enzyme gene was HAS1. In the Wnt signaling pathway, the genes for Wnt-5a and low-density lipoprotein receptor–related protein 5 were up-regulated, while the gene FZD2 and the gene for Dkk-3 were down-regulated. Finally, STC1, which codes for a protein involved in angiogenesis, was identified as the most up-regulated gene in inflamed compared with normal/reactive areas. Conclusion This study is the first to identify different expression patterns between 2 areas of the synovial membrane from the same patient. These differences concern several key pathways involved in OA pathogenesis. This analysis also provides information regarding new genes and proteins as potential targets of treatment. PMID:24757147

  6. Precancerous lesions of oral mucosa

    PubMed Central

    Yardimci, Gurkan; Kutlubay, Zekayi; Engin, Burhan; Tuzun, Yalcin

    2014-01-01

    Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaque-like, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary. The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used. PMID:25516862

  7. Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC

    PubMed Central

    Castagliuolo, Ignazio; Erroi, Francesca; Kotsafti, Andromachi; Basato, Silvia; Brun, Paola; D'Incà, Renata; Rugge, Massimo

    2016-01-01

    Background Promoter hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. Results The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. Methods Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. Conclusions Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance. PMID:26862732

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

    PubMed

    Roager, Henrik M; Hansen, Lea B S; Bahl, Martin I; Frandsen, Henrik L; Carvalho, Vera; Gøbel, Rikke J; Dalgaard, Marlene D; Plichta, Damian R; Sparholt, Morten H; Vestergaard, Henrik; Hansen, Torben; Sicheritz-Pontén, Thomas; Nielsen, H Bjørn; Pedersen, Oluf; Lauritzen, Lotte; Kristensen, Mette; Gupta, Ramneek; Licht, Tine R

    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 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 to protein catabolism as reflected by higher urinary levels of potentially deleterious protein-derived metabolites. Additionally, shorter colonic transit time correlates with metabolites possibly reflecting increased renewal of the colonic mucosa. Together, this suggests that a high gut microbial richness 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. PMID:27562254

  9. Microbial dysbiosis and colon carcinogenesis: could colon cancer be considered a bacteria-related disease?

    PubMed Central

    Amiot, Aurelien; Le Baleur, Yann; Levy, Michael; Auriault, Marie-Luce; Van Nhieu, Jeanne Tran; Delchier, Jean Charles

    2013-01-01

    Colorectal cancer (CRC) is posing an increasingly important burden on the health care system, with western countries seeing a growing incidence of the disease. Except for germline DNA mutations which have been attributed to less than 5% of patients, little is known about the main causes of CRC. However, environment factors such as food, lifestyle and medication are now suspected to have a major influence on inducing cancers. Today, exhaustive quantitative and qualitative evaluation of all environmental factors is not possible. Various environment-induced diseases have been characterized based on colon microflora, also called microbiota, analyses. Growing data have shown specific changes in microflora (i.e. dysbiosis) in the stools of patients with colon cancer or those adherent to the colonic mucosa. Thus, it appears that microbiota may be considered a platform offering host and environment interactions for studying CRCs. The hypothesis that colon cancer might be a bacteria-related disease is suggested and perspectives are discussed. PMID:23634186

  10. Space colonization.

    PubMed

    2002-12-01

    NASA interest in colonization encompasses space tourism; space exploration; space bases in orbit, at L1, on the Moon, or on Mars; in-situ resource utilization; and planetary terraforming. Activities progressed during 2002 in areas such as Mars colonies, hoppers, and biomass; space elevators and construction; and in-situ consumables. PMID:12506926

  11. Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

    PubMed Central

    Park, Jae Hyung; Kwon, Joong Goo; Kim, Sun Joo; Song, Dae Kyu; Lee, Seok Guen; Kim, Eun Su; Cho, Kwang Bum; Jang, Byung Ik; Kim, Dae Hwan; Sin, Jeong-Im; Kim, Tae Wan; Song, In Hwan; Park, Kyung Sik

    2015-01-01

    Background/Aims Inflammatory bowel disease is commonly accompanied by colonic dysmotility and causes changes in intestinal smooth muscle contractility. In this study, colonic smooth muscle contractility in a chronic inflammatory condition was investigated using smooth muscle tissues prepared from interleukin-10 knockout (IL-10−/−) mice. Methods Prepared smooth muscle sections were placed in an organ bath system. Cholinergic and nitrergic neuronal responses were observed using carbachol and electrical field stimulation with L-NG-nitroarginine methyl ester (L-NAME). The expression of interstitial cells of Cajal (ICC) networks, muscarinic receptors, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was observed via immunofluorescent staining. Results The spontaneous contractility and expression of ICC networks in the proximal and distal colon was significantly decreased in IL-10−/− mice compared to IL-10+/+ mice. The contractility in response to carbachol was significantly decreased in the proximal colon of IL-10−/− mice compared to IL-10+/+ mice, but no significant difference was found in the distal colon. In addition, the expression of muscarinic receptor type 2 was reduced in the proximal colon of IL-10−/− mice. The nictric oxide-mediated relaxation after electrical field stimulation was significantly decreased in the proximal and distal colon of IL-10−/− mice. In inflamed colon, the expression of nNOS decreased, whereas the expression of iNOS increased. Conclusions These results suggest that damage to the ICC network and NOS system in the proximal and distal colon, as well as damage to the smooth muscle cholinergic receptor in the proximal colon may play an important role in the dysmotility of the inflamed colon. PMID:25537671

  12. [Vesiculobullous lesions of the oral mucosa].

    PubMed

    Spijkervet, F K; Vissink, A; Raghoebar, G M; van der Waal, I

    2001-06-01

    In general practice, the dentist can be confronted with a vesiculobullous lesion of the oral mucosa. In many cases the lesion can be classified as recurrent herpes labialis, but many other causes can induce a vesiculobullous lesion of the oral mucosa and perioral skin as well. This article gives an overview of the various vesiculous and bullous lesions of the oral mucous membranes. Special attention is given to the possible causes and their treatment. PMID:11441714

  13. Autofluorescence spectroscopy of oral mucosa

    NASA Astrophysics Data System (ADS)

    Majumdar, S. K.; Uppal, A.; Gupta, P. K.

    1998-06-01

    We report the results of an in-vitro study on autofluorescence from pathologically characterized normal and malignant squamous tissues from the oral cavity. The study involved biopsy samples from 47 patients with oral cancer of which 11 patients had cancer of tongue, 17 of buccal mucosa and 19 of alveolus. The results of excitation and emission spectroscopy at several wavelengths (280 nm less than or equal to (lambda) exless than or equal to 460 nm; 340 nm less than or equal to (lambda) em less than or equal to 520 nm) showed that at (lambda) ex equals 337 nm and 400 nm the mean value for the spectrally integrated fluorescence intensity [(Sigma) (lambda ) IF((lambda) )] from the normal tissue sites was about a factor of 2 larger than that from the malignant tissue sites. At other excitation wavelengths the difference in (Sigma) (lambda ) IF((lambda) ) was not statistically significant. Similarly, for (lambda) em equals 390 nm and 460 nm, the intensity of the 340 nm band of the excitation spectra from normal tissues was observed to be a factor of 2 larger than that from malignant tissues. Analysis of these results suggests that NADH concentration is higher in normal oral tissues compared to the malignant. This contrasts with our earlier observation of an reduced NADH concentration in normal sites of breast tissues vis a vis malignant sites. For the 337 nm excited emission spectra a 10-variable MVLR score (using (Sigma) (lambda ) IF((lambda) ) and normalized intensities at nine wavelengths as input parameters) provided a sensitivity and specificity of 95.7% and 93.1% over the sample size investigated.

  14. Invasion by Neisseria meningitidis varies widely between clones and among nasopharyngeal mucosae derived from adult human hosts.

    PubMed

    Townsend, Robert; Goodwin, Linda; Stevanin, Tania M; Silcocks, Paul B; Parker, Andrew; Maiden, Martin C J; Read, Robert C

    2002-05-01

    Colonization of the human nasopharynx is a feature of some species of Neisseria, and is a prerequisite of invasive meningococcal disease. The likelihood of colonization by Neisseria meningitidis varies widely between humans, and very few develop invasive disease. Explants of nasal mucosa derived from adult patients with non-allergic nasal obstruction were infected experimentally with Neisseria spp. At intervals over 18 h incubation, washed explants were homogenized, and viable bacteria were counted. To estimate bacterial invasion of mucosa, explants were exposed to 0.25% sodium taurocholate for 30 s prior to homogenization. N. meningitidis was recovered from the mucosa and the organism invaded and replicated within the tissue, in contrast to N. lactamica and N. animalis (n=9, P<0.008). N. meningitidis isolates of clones ET-5, ET-37 and lineage III were recovered from and invaded tissue, but strains of clones A4, A:subgroup I, A:subgroup III and A:subgroup IV-1 did not invade (n=6). To measure host variation, survival of N. meningitidis within nasal mucosa of 40 different human donors was measured. Intra-class correlation of replicates was 0.97, but the coefficient of variation of recovered viable counts was 1335% after 4 h and 77% after 18 h incubation. It is concluded that the distinctive colonization and disease potential of Neisseria spp. may be partly a consequence of their ability to invade and survive within human nasopharyngeal mucosa, but that this is influenced greatly by genetic or environmental factors operating on the host mucosa. This is consistent with the unpredictable epidemiology of meningococcal disease. PMID:11988521

  15. Immunoregulatory function of human intestinal mucosa lymphoid cells: evidence for enhanced suppressor cell activity in inflammatory bowel disease.

    PubMed Central

    Fiocchi, C; Youngman, K R; Farmer, R G

    1983-01-01

    Abnormalities in immune regulation at the gut level may be relevant to the pathogenesis of inflammatory bowel disease, but little is known about the immunoregulatory properties of intestinal mononuclear cells. Therefore, we wished to see if lymphoid cells derived from the lamina propria of surgically resected bowel specimens have any modulatory effect upon the immune response of peripheral blood mononuclear cells from patients with ulcerative colitis or Crohn's disease. When autologous peripheral blood and intestinal lamina propria lymphoid cells were mixed at different ratios and cultured in the presence of phytohaemagglutinin, we were able to show that intestinal mononuclear cells had the capacity to modify the mitogenic response of the cultured cells. These intestinal immunoregulatory cells, when obtained from mucosa affected by inflammatory bowel disease, express a significantly enhanced suppressor cell activity as compared with those from non-inflamed control mucosa. Such suppressor cell activity varies with cell concentration and requires cell proliferation, but it is independent of anatomical origin (small vs large bowel), type of inflammatory bowel disease (ulcerative colitis vs Crohn's disease) or immunosuppressive therapy. These findings point to an important functional difference between inflammatory bowel disease and control intestinal mucosa mononuclear cells. The enhanced suppressor activity of lamina propria mononuclear cells may be associated with impairment of cell-mediated immunity at the gut level. This may be related to the pathogenesis of inflammatory bowel disease by leading to defective intestinal immune regulatory events, which may not be detectable at the peripheral level. PMID:6223862

  16. Antispasmodic effects of myrrh due to calcium antagonistic effects in inflamed rat small intestinal preparations.

    PubMed

    Vissiennon, Cica; Goos, Karl-Heinz; Goos, Ole; Nieber, Karen

    2015-01-01

    Myrrh is the oleo-gum resin of mainly Commiphora molmol and as a powdered substance, one compound in the traditional medicinal product Myrrhinil-Intest®, which has been used for the treatment of unspecific, inflammatory intestinal disorders. The aim of the present study was to evaluate the antispasmodic effect of myrrh under healthy and inflamed conditions, and to evaluate a calcium-antagonistic effect as a possible mode of action. Therefore, an ethanolic myrrh extract was tested for its effects on muscle tone and acetylcholine-induced contractions in untreated and inflamed rat ileum/jejunum preparations. Inflammation was experimentally induced by 2,4,6-trinitrobenzene sulfonic acid (10 mM, 30 min). Additionally, the effect of the calcium channel agonist Bay K8644 in the presence of varying myrrh extract concentrations was examined. Myrrh extract (0.99 mg/mL) suppressed the acetylcholine-induced contraction down to 25.8 % in untreated and 15.2 % in inflamed preparations. Myrrh extract (0.15; 0.25 and 0.35 mg/mL) induced a concentration-dependent rightward shift of the Bay K8644 concentration-response curve in untreated and inflamed preparations with a significant EC50 shift. Schild analysis resulted in a pA2 value of 0.93 for untreated preparations. Increasing myrrh extract concentrations induced a concentration-dependent decrease of the agonistic maximum effect in untreated and inflamed preparations down to 15.8 % and 25.8 %, respectively, for the highest concentration leading to a pD2 value of 0.58. Myrrh extract reduced intestinal muscle tone and acetylcholine-induced contraction of untreated and inflamed ileum/jejunum preparations based on dual calcium antagonism characterized by a right shift of the agonistic dose-response curve and a depression of the maximum effect. The resulting reduction of intestinal motility and spasmolytic effects provide a rationale for the symptom treatment of intestinal disorders such as irritable bowel syndrome

  17. Enhanced endoscopic detection of early colon cancer

    NASA Astrophysics Data System (ADS)

    Balachandar, Gowra; Trowers, Eugene A.

    1999-06-01

    Enhanced endoscopic detection of small flat adenomas is becoming increasingly important as they have a reported 14 percent incidence of dysplasia when compared with 5% incidence in polypod adenomas of the same size. These lesions even when invasive do not show up against the translucent surrounding mucosa making endoscopic detection difficult. Dye spraying with indigo carmine makes their morphology clear, with well-circumscribed borders. Dye spraying and magnifying endoscopes can be used to observe pit patterns on the surface of the bowel. Combining dye spraying and high-resolution video endoscopy demonstrates well the colorectal epithelial surface. Scanning immersion video endoscopy visualizes the epithelial surface of the colorectal mucosa by high-resolution endoscopy after filling the lumen with water. Endoscopic ultrasound can be used to see if the lesion is intramucosal or not and assess the depth of invasion if malignancy is presented. Laser induced fluorescence spectroscopy has the potential to detect colonic dysplasia in vivo. Combining such technologies with conventional colonoscopy can help in the surveillance of large areas of colonic mucosa for the presence of dysplasia. Guided biopsy can replace random biopsy based on information provided at the time of colonoscopic examination.

  18. Autofluorescence ratio imaging of human colonic adenomas

    NASA Astrophysics Data System (ADS)

    Imaizumi, Katsuichi; Harada, Yoshinori; Wakabayashi, Naoki; Yamaoka, Yoshihisa; Dai, Ping; Tanaka, Hideo; Takamatsu, Tetsuro

    2011-02-01

    Recently autofluorescence imaging (AFI) endoscopy, visualizing tissue fluorescence in combination with reflected light, has been adopted as a technique for detecting neoplasms in the colon and other organs. However, autofluorescence colonoscopy is not infallible, and improvement of the detection method can be expected to enhance the performance. Colonic mucosa contains metabolism-related fluorophores, such as reduced nicotinamide adenine dinucleotide, which may be useful for visualizing neoplasia in autofluorescence endoscopy. We examined sliced cross-sections of endoscopically resected tubular adenomas under a microscope. Fluorescence images acquired at 365-nm excitation (F365ex) and 405-nm excitation (F405ex), and reflectance images acquired at 550 nm (R550) were obtained. Fluorescence ratio (F365ex/F405ex) images and reflectance/fluorescence ratio (R550/F405ex) images were calculated from the acquired images. The fluorescence ratio images could distinguish adenomatous mucosa from normal mucosa more clearly than the reflectance/fluorescence ratio images. The results showed that the autofluorescence ratio imaging is a potential technique for increasing the diagnostic power of autofluorescence endoscopy.

  19. Fructose-Asparagine Is a Primary Nutrient during Growth of Salmonella in the Inflamed Intestine

    PubMed Central

    Ali, Mohamed M.; Newsom, David L.; González, Juan F.; Sabag-Daigle, Anice; Stahl, Christopher; Steidley, Brandi; Dubena, Judith; Dyszel, Jessica L.; Smith, Jenee N.; Dieye, Yakhya; Arsenescu, Razvan; Boyaka, Prosper N.; Krakowka, Steven; Romeo, Tony; Behrman, Edward J.; White, Peter; Ahmer, Brian M. M.

    2014-01-01

    Salmonella enterica serovar Typhimurium (Salmonella) is one of the most significant food-borne pathogens affecting both humans and agriculture. We have determined that Salmonella encodes an uptake and utilization pathway specific for a novel nutrient, fructose-asparagine (F-Asn), which is essential for Salmonella fitness in the inflamed intestine (modeled using germ-free, streptomycin-treated, ex-germ-free with human microbiota, and IL10−/− mice). The locus encoding F-Asn utilization, fra, provides an advantage only if Salmonella can initiate inflammation and use tetrathionate as a terminal electron acceptor for anaerobic respiration (the fra phenotype is lost in Salmonella SPI1− SPI2− or ttrA mutants, respectively). The severe fitness defect of a Salmonella fra mutant suggests that F-Asn is the primary nutrient utilized by Salmonella in the inflamed intestine and that this system provides a valuable target for novel therapies. PMID:24967579

  20. Effective anaesthesia of the acutely inflamed pulp: part 2. Clinical strategies.

    PubMed

    Virdee, S S; Bhakta, S; Seymour, D

    2015-11-13

    Achieving profound pulpal anaesthesia in a mandibular molar diagnosed with irreversible pulpitis can be argued to be the most testing of dental anaesthetic challenges. Following discussion on the possible reasons for this occurrence in part 1, part 2 outlines the various local anaesthetic techniques that practitioners can use to overcome the acutely inflamed mandibular molar. They should then be able to apply these same principles to help anaesthetise any other tooth presenting with an acutely inflamed pulp. Techniques are discussed in detail along with key variables that have been associated with having an impact on the anaesthetic efficacy. This is to bring to light factors that can aid anaesthetic success as well as dispel common misnomers. PMID:26564355

  1. Fournier's gangrene secondary to an acutely inflamed appendix herniating into the deep inguinal ring

    PubMed Central

    Sarmah, Piyush B.; Khan, Mashuk; Zilvetti, Miguel

    2015-01-01

    Fournier's gangrene (FG) requires prompt recognition and management. We report the case of a 68-year-old man who presented with extensive pain and purple discolouration from the right iliac fossa to perineum. Computed tomography demonstrated gas within the right hemiscrotum extending into the inguinal canal and right buttock, with a right pelvic fluid and air collection. At debridement necrotic fluid was arising from the superficial inguinal ring so laparotomy was performed, revealing a grossly inflamed appendix herniating into the inguinal canal; a right hemicolectomy was performed. Unfortunately, the patient went into cardiac arrest and passed away on the operating table. Histological analysis demonstrated acute-on-chronic inflammation involving the appendix. The condition where appendicitis is implicated in FG is usually due to retroperitoneal rupture and tracking into the perineal spaces. This is the first case reported of an inflamed appendix herniating into the inguinal canal and thus causing FG. PMID:25829533

  2. Increased Apoptosis of Inflamed Odontoblasts Is Associated with CD47 Loss.

    PubMed

    Wang, H S; Pei, F; Chen, Z; Zhang, L

    2016-06-01

    Survival of odontoblasts during infection and inflammation determines prognosis of the dental pulp. CD47 is a "self"-label surface marker on viable cells. The aim of the present study is to investigate the interaction between CD47, autophagy, and apoptosis in inflamed human dental pulp and lipopolysaccharide (LPS)-treated mDPC6T cells. We identified activation of autophagy and apoptosis in the odontoblasts due to inflammation of the human dental pulp. Furthermore, downregulation of CD47 correlated with increased autophagy and apoptosis in dental pulp of the patients afflicted with either caries and/or pulpitis. We also detected colocalization of CD47 and LC3 in the inflamed odontoblasts. In addition, functional study indicated that loss of CD47 activates autophagy and increases apoptosis, indicating that CD47 plays a key role in the LPS-induced autophagy and apoptosis of odontoblasts. PMID:26912219

  3. A time-dependent degeneration manner of condyle in rat CFA-induced inflamed TMJ.

    PubMed

    Xu, Liqin; Guo, Huilin; Li, Cheng; Xu, Jie; Fang, Wei; Long, Xing

    2016-01-01

    Temporomandibular joint (TMJ) inflammation is a potential risk factor of osteoarthritis (OA) but the detailed degenerative changes in the inflamed TMJ remain unclear. In this study, we evaluated the changes of condylar cartilage and subchondral bone in rat inflamed TMJ induced by Freund's complete adjuvant (CFA). Articular cavity was injected with CFA and the TMJ samples were collected 1, 2, 3, and 4-week post-injection. Hematoxylin & Eosin (H&E) staining, toluidine blue (TB) staining, Safranin O (S.O) staining, Masson trichrome staining and micro-CT were used to assess TMJ degeneration during inflammation. Osteoclast and osteoblast activities were analyzed by tartrate-resistant acid phosphatase (TRAP) staining and osteocalcin (OCN) immunohistochemistry staining respectively. The expression of receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) in condylar cartilage and subchondral bone was also evaluated through immunohistochemistry and RANKL/OPG ratio was evaluated. Reduced cartilage thickness, decreased number of chondrocytes, and down-regulated proteoglycan expression were observed in the condylar cartilage in the inflamed TMJ. Enhanced osteoclast activity, and expanded bone marrow cavity were reached the peak in the 2-week after CFA-injection. Meanwhile the RANKL/OPG ratio in the cartilage and subchondral bone also increased in the 2-week CFA-injection. Immature, unmineralized new bones with irregular trabecular bone structure, atypical condylar shape, up-regulated OCN expression, and decreased bone mineral density (BMD) were found in the inflamed TMJ. The time-dependent degeneration manner of TMJ cartilage and subchondral bone was found in CFA-induced arthritis rat model. The degeneration in the TMJ with inflammation might be a risk factor and should be concerned. PMID:27158347

  4. The Next Hurdle in Cancer Immunotherapy: Overcoming the Non-T-Cell-Inflamed Tumor Microenvironment.

    PubMed

    Gajewski, Thomas F

    2015-08-01

    A growing body of evidence suggests that a major subset of patients with advanced solid tumors shows evidence for a T-cell-inflamed tumor microenvironment. This phenotype has positive prognostic value for several types of early stage cancer, suggesting that the attempt by the host to generate an anti-tumor immune response reflects a biologic process associated with improved patient outcomes. In metastatic disease, the presence of this phenotype appears to be associated with clinical response to several immunotherapies, including cancer vaccines, checkpoint blockade, and adoptive T-cell transfer. With the high rate of clinical response to several of these therapies, along with early data indicating that combination immunotherapies may be even more potent, it seems likely that effective immune-based therapies will become a reality for patients with a range of different cancers that physiologically support the T-cell-inflamed tumor microenvironment in a subset of individuals. Therefore, one of the next significant hurdles will be to develop new therapeutic interventions that will enable these immunotherapies to be effective in patients with the non-T-cell-inflamed phenotype. Rational development of such interventions will benefit from a detailed molecular understanding of the mechanisms that explain the presence or absence of the T-cell-inflamed tumor microenvironment, which in turn will benefit from focused interrogation of patient samples. This iterative "reverse-translational" research strategy has already identified new candidate therapeutic targets and approaches. It is envisioned that the end result of these investigations will be an expanded array of interventions that will broaden the fraction of patients benefitting from immunotherapies in the clinic. PMID:26320069

  5. VEGF-A produced by chronically inflamed tissue induces lymphangiogenesis in draining lymph nodes

    PubMed Central

    Halin, Cornelia; Tobler, Nadja E.; Vigl, Benjamin; Brown, Lawrence F.

    2007-01-01

    Lymphangiogenesis is involved in tumor cell metastasis and plays a major role in chronic inflammatory disorders. To investigate the role of lymphangiogenesis in inflammation, we induced and maintained delayed-type hypersensitivity (DTH) reactions in the ears of mice and then analyzed the resulting lymphangiogenesis in the inflamed tissue and draining lymph nodes (LNs) by quantitative fluorescence-activated cell sorting (FACS) and by immunofluorescence. Long-lasting inflammation induced a significant increase in the number of lymphatic endothelial cells, not only in the inflamed ears but also in the ear-draining auricular LNs. Inflammation-induced lymphangiogenesis was potently blocked by systemic administration of a vascular endothelial growth factor (VEGF)-A neutralizing antibody. Surprisingly, tissue inflammation specifically induced LN lymphangiogenesis but not LN angiogenesis. These findings were explained by analysis of both VEGF-A protein and mRNA levels, which revealed that VEGF-A was expressed at high mRNA and protein levels in inflamed ears but that expression was increased only at the protein level in activated LNs. Inflammation-induced lymphangiogenesis in LNs was independent of the presence of nodal B lymphocytes, as shown in B cell-deficient mice. Our data reveal that chronic inflammation actively induces lymphangiogenesis in LNs, which is controlled remotely, by lymphangiogenic factors produced at the site of inflammation. PMID:17625067

  6. Matrix metalloproteinases modulate ameboid-like migration of neutrophils through inflamed interstitial tissue

    PubMed Central

    Lerchenberger, Max; Uhl, Bernd; Stark, Konstantin; Zuchtriegel, Gabriele; Eckart, Annekathrin; Miller, Meike; Puhr-Westerheide, Daniel; Praetner, Marc; Rehberg, Markus; Khandoga, Alexander G.; Lauber, Kirsten; Massberg, Steffen; Krombach, Fritz

    2013-01-01

    In vitro studies suggest that leukocytes locomote in an ameboid fashion independently of pericellular proteolysis. Whether this motility pattern applies for leukocyte migration in inflamed tissue is still unknown. In vivo microscopy on the inflamed mouse cremaster muscle revealed that blockade of serine proteases or of matrix metalloproteinases (MMPs) significantly reduces intravascular accumulation and transmigration of neutrophils. Using a novel in vivo chemotaxis assay, perivenular microinjection of inflammatory mediators induced directional interstitial migration of neutrophils. Blockade of actin polymerization, but not of actomyosin contraction abolished neutrophil interstitial locomotion. Multiphoton laser scanning in vivo microscopy showed that the density of the interstitial collagen network increases in inflamed tissue, thereby providing physical guidance to infiltrating neutrophils. Although neutrophils locomote through the interstitium without pericellular collagen degradation, inhibition of MMPs, but not of serine proteases, diminished their polarization and interstitial locomotion. In this context, blockade of MMPs was found to modulate expression of adhesion/signaling molecules on neutrophils. Collectively, our data indicate that serine proteases are critical for neutrophil extravasation, whereas these enzymes are dispensable for neutrophil extravascular locomotion. By contrast, neutrophil interstitial migration strictly relies on actin polymerization and does not require the pericellular degradation of collagen fibers but is modulated by MMPs. PMID:23757732

  7. Expression of the duffy antigen/receptor for chemokines (DARC) by the inflamed synovial endothelium.

    PubMed

    Patterson, Angela M; Siddall, Hilary; Chamberlain, Giselle; Gardner, Lucy; Middleton, Jim

    2002-05-01

    The expression of chemokine binding sites on the endothelial cells of venules in inflamed synovia was examined and whether the Duffy antigen/receptor for chemokines (DARC) was involved. In situ binding assays were performed to determine the expression of chemokine binding sites from rheumatoid (n = 10) and non-rheumatoid (n = 10) synovia. The expression of DARC protein and mRNA was examined by immunohistochemistry and northern blotting. The involvement of DARC in chemokine binding was studied by incubating sections with blocking antibodies to DARC (Fy3 and 6), to find out if these reduced 125I-IL-8 binding. Binding of radiolabelled chemokines IL-8, RANTES, MCP-1, but not MIP-1alpha, was found on venular endothelial cells in inflamed synovia from both rheumatoid and non-rheumatoid patients. Excess homologous unlabelled chemokine displaced binding and excess unlabelled RANTES could displace radiolabelled IL-8 binding. DARC protein expression was demonstrated on venular endothelial cells in all samples and DARC mRNA could be detected in extracts from synovia. There was downregulation of DARC protein and mRNA in rheumatoid samples. Binding of IL-8 to both rheumatoid and non-rheumatoid synovia was significantly reduced in the presence of anti-DARC Fy3 and Fy6 monoclonal antibodies. These findings show the expression of a multispecific chemokine binding site on the inflamed synovial endothelium, with evidence for involvement of DARC. This suggests a potential role for DARC in the inflammatory processes involved in synovitis. PMID:12081195

  8. Passage of a Sigmoid Colon Cast in a Patient With Ischemic Colitis

    PubMed Central

    Abe, Shinya; Yamaguchi, Hironori; Murono, Koji; Kanazawa, Takamitsu; Ishihara, Souichirou; Sunami, Eiji; Watanabe, Toshiaki

    2014-01-01

    Colon cast passage, which is the spontaneous passage of a full-thickness, infarcted colonic segment per rectum, is a rare occurrence. The main cause is acute ischemic colitis resulting from a circulation compromise. Most of the colon cast cases reported were secondary to abdominal aortic aneurysm repairs or colorectal surgery. We report a case of an 80-year-old woman with ischemic colitis who excreted a 20-cm colon cast. In most cases that involve a colon cast containing a muscle layer component, invasive therapy is required owing to colonic obstruction or stenosis. However, in the present case, the colon cast consisted only of a mucosa layer and was not associated with severe stenosis or obstruction; therefore, it was successfully treated by conservative therapy. Histologic examination of the colon segment may be crucial in determining the appropriate treatment. PMID:25216411

  9. Effect of indigestible saccharides on B lymphocyte response of intestinal mucosa and cecal fermentation in rats.

    PubMed

    Kudoh, K; Shimizu, J; Wada, M; Takita, T; Kanke, Y; Innami, S

    1998-02-01

    The effects of water-soluble and -insoluble indigestible saccharides (IDS) on immune responses of the intestinal tract were studied. Male 4-week-old Sprague Dawley rats were fed for three weeks on diets containing several kinds of IDS at 5%. The results revealed that the proportion of kappa-light chain and IgA-presenting lymphocytes in small intestinal and cecal mucosa differed in increased number depending on the type of IDS. The response of colonic mucosa was not pronounced. The amounts of short-chain fatty acid (SCFA) and lactic acid in the cecal contents of the other test groups except the celfur group tended to be higher than those in the cellulose group, particularly in the lactulose group where many acids showed significant increases. The correlation between the proportion of kappa-light chain and IgA-presenting lymphocytes in the cecal mucosa and lactic acid in the cecal contents was significant, but that between the proportion of both lymphocytes and SCFA was not. Based on the above, we concluded that the oral administration of IDS induces the proliferation of kappa-light chain and IgA-producing B lymphocytes in small intestinal and cecal mucosa, but the degree of response differs depending on the type of IDS. It is thus suggested that IDS are involved in the intestinal immune system of rats. PMID:9591238

  10. Determination of optical properties of normal and adenomatous human colon tissues in vitro using integrating sphere techniques

    PubMed Central

    Wei, Hua-Jiang; Xing, Da; Lu, Jian-Jun; Gu, Huai-Min; Wu, Guo-Yong; Jin, Ying

    2005-01-01

    AIM: The purpose of the present study is to compare the optical properties of normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion in vitro at 476.5, 488, 496.5, 514.5 and 532 nm. We believe these differences in optical properties should help differential diagnosis of human colon tissues by using optical methods. METHODS: In vitro optical properties were investigated for four kinds of tissues: normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion. Tissue samples were taken from 13 human colons (13 adenomatous, 13 normal). From the normal human colons a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion), and from the adenomatous human bladders a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion). The measurements were performed using a double-integrating-sphere setup and the optical properties were assessed from these measurements using the adding-doubling method that was considered reliable. RESULTS: The results of measurement showed that there were significant differences in the absorption coefficients and scattering coefficients between normal and adenomatous human colon mucosa/submucosa at the same wavelength, and there were also significant differences in the two optical parameters between both colon muscle layer/chorion at the same wavelength. And there were large differences in the anisotropy factors between both colon mucosa/submucosa at the same wavelength, there were also large differences in the anisotropy factors between both colon muscle layer/chorion at the same wavelength. There were large differences in the value ranges of the absorption coefficients, scattering coefficients and anisotropy factors between both colon mucosa/submucosa, and

  11. Salmonella induces prominent gene expression in the rat colon

    PubMed Central

    Rodenburg, Wendy; Keijer, Jaap; Kramer, Evelien; Roosing, Susanne; Vink, Carolien; Katan, Martijn B; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg MJ

    2007-01-01

    Background Salmonella enteritidis is suggested to translocate in the small intestine. In vivo it induces gene expression changes in the ileal mucosa and Peyer's patches. Stimulation of Salmonella translocation by dietary prebiotics fermented in colon suggests involvement of the colon as well. However, effects of Salmonella on colonic gene expression in vivo are largely unknown. We aimed to characterize time dependent Salmonella-induced changes of colonic mucosal gene expression in rats using whole genome microarrays. For this, rats were orally infected with Salmonella enteritidis to mimic a foodborne infection and colonic gene expression was determined at days 1, 3 and 6 post-infection (n = 8 rats per time-point). As fructo-oligosaccharides (FOS) affect colonic physiology, we analyzed colonic mucosal gene expression of FOS-fed versus cellulose-fed rats infected with Salmonella in a separate experiment. Colonic mucosal samples were isolated at day 2 post-infection. Results Salmonella affected transport (e.g. Chloride channel calcium activated 6, H+/K+ transporting Atp-ase), antimicrobial defense (e.g. Lipopolysaccharide binding protein, Defensin 5 and phospholipase A2), inflammation (e.g. calprotectin), oxidative stress related genes (e.g. Dual oxidase 2 and Glutathione peroxidase 2) and Proteolysis (e.g. Ubiquitin D and Proteosome subunit beta type 9). Furthermore, Salmonella translocation increased serum IFNγ and many interferon-related genes in colonic mucosa. The gene most strongly induced by Salmonella infection was Pancreatitis Associated Protein (Pap), showing >100-fold induction at day 6 after oral infection. Results were confirmed by Q-PCR in individual rats. Stimulation of Salmonella translocation by dietary FOS was accompanied by enhancement of the Salmonella-induced mucosal processes, not by induction of other processes. Conclusion We conclude that the colon is a target tissue for Salmonella, considering the abundant changes in mucosal gene expression

  12. Radiation tolerance of the vaginal mucosa

    SciTech Connect

    Hintz, b.L.; Kagan, A.R.; Chan, P.; Gilbert, H.A.; Nussbaum, H.; Rao, A.R.; Wollin, M.

    1980-06-01

    Sixteen patients with cancer of the vagina that were controlled locally for a minimum of eighteen months after teletherpay (T) or brachytherapy (B) or both (T and B), were analyzed for radiation tolerance of the vaginal mucosa. The site of vaginal necrosis did not always coincide with the site of the tumor. The posterior wall appeared more vulnerable than the anterior or lateral walls. For the distal vaginal mucosa, necrosis requiring surgical intervention occurred following combined T and B, if summated rad exceeded9800. The upper vagina tolerated higher dosages. No patient surgery for upper vaginal necrosis even though summated (T and B) dosage up to 14,000 rad was applied. Placing radioactive needles on the surface of the vaginal cylinder with or without interstitial perincal needles should be avoided. Further accumulation of data is needed to define these vaginal mucosa tolerance limits more closely.

  13. Eukaryotic and prokaryotic contributions to colonic hydrogen sulfide synthesis.

    PubMed

    Flannigan, Kyle L; McCoy, Kathy D; Wallace, John L

    2011-07-01

    Hydrogen sulfide (H(2)S) is an important modulator of many aspects of digestive function, both in health and disease. Colonic tissue H(2)S synthesis increases markedly during injury and inflammation and appears to contribute to resolution. Some of the bacteria residing in the colon can also produce H(2)S. The extent to which bacterial H(2)S synthesis contributes to what is measured as colonic H(2)S synthesis is not clear. Using conventional and germ-free mice, we have delineated the eukaryotic vs. prokaryotic contributions to colonic H(2)S synthesis, both in healthy and colitic mice. Colonic tissue H(2)S production is entirely dependent on the presence of the cofactor pyridoxal 5'-phosphate (vitamin B(6)), while bacterial H(2)S synthesis appears to occur independent of this cofactor. As expected, approximately one-half of the H(2)S produced by feces is derived from eukaryotic cells. While colonic H(2)S synthesis is markedly increased when the tissue is inflamed, and, in proportion to the extent of inflammation, fecal H(2)S synthesis does not change and tissue granulocytes do not appear to be the source of the elevated H(2)S production. Rats fed a B vitamin-deficient diet for 6 wk exhibited significantly diminished colonic H(2)S synthesis, but fecal H(2)S synthesis was not different from that of rats on the control diet. Our results demonstrate that H(2)S production by colonic bacteria does not contribute significantly to what is measured as colonic tissue H(2)S production, using the acetate trapping assay system employed in this study. PMID:21474649

  14. Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover

    PubMed Central

    Gibson, P; Birchall, I; Rosella, O; Albert, V; Finch, C; Barkla, D; Young, G

    1998-01-01

    Background—The functions of urokinase in intestinal epithelia are unknown. 
Aims—To determine the relation of urokinase expressed by intestinal epithelial cells to their position in the crypt-villus/surface axis and of mucosal urokinase activity to epithelial proliferative kinetics in the distal colon. 
Methods—Urokinase expression was examined immunohistochemically in human intestinal mucosa. Urokinase activity was measured colorimetrically in epithelial cells isolated sequentially from the crypt-villus axis of the rat small intestine. In separate experiments, urokinase activity and epithelial kinetics (measured stathmokinetically) were measured in homogenates of distal colonic mucosa of 14 groups of eight rats fed diets known to alter epithelial turnover. 
Results—From the crypt base, an ascending gradient of expression and activity of urokinase was associated with the epithelial cells. Median mucosal urokinase activities in each of the dietary groups of rats correlated positively with autologous median number of metaphase arrests per crypt (r=0.68; p<0.005) and per 100 crypt cells (r=0.75; p<0.001), but not with crypt column height. 
Conclusions—Localisation of an enzyme capable of leading to digestion of cell substratum in the region where cells are loosely attached to their basement membrane, and the association of its activity with indexes of cell turnover, suggest a role for urokinase in facilitating epithelial cell loss in the intestine. 

 Keywords: urokinase; intestinal epithelium; colon; epithelial proliferation PMID:9824347

  15. Colon cancer - resources

    MedlinePlus

    Resources - colon cancer ... The following organizations are good resources for information on colon cancer : American Cancer Society -- www.cancer.org/cancer/colonandrectumcancer/index Colon Cancer Alliance -- www.ccalliance.org National ...

  16. Butyrate attenuates lipopolysaccharide-induced inflammation in intestinal cells and Crohn's mucosa through modulation of antioxidant defense machinery.

    PubMed

    Russo, Ilaria; Luciani, Alessandro; De Cicco, Paola; Troncone, Edoardo; Ciacci, Carolina

    2012-01-01

    Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease (CrD). High levels of Reactive Oxygen Species (ROS) induce the activation of the redox-sensitive nuclear transcription factor kappa-B (NF-κB), which in turn triggers the inflammatory mediators. Butyrate decreases pro-inflammatory cytokine expression by the lamina propria mononuclear cells in CrD patients via inhibition of NF-κB activation, but how it reduces inflammation is still unclear. We suggest that butyrate controls ROS mediated NF-κB activation and thus mucosal inflammation in intestinal epithelial cells and in CrD colonic mucosa by triggering intracellular antioxidant defense systems. Intestinal epithelial Caco-2 cells and colonic mucosa from 14 patients with CrD and 12 controls were challenged with or without lipopolysaccaride from Escherichia coli (EC-LPS) in presence or absence of butyrate for 4 and 24 h. The effects of butyrate on oxidative stress, p42/44 MAP kinase phosphorylation, p65-NF-κB activation and mucosal inflammation were investigated by real time PCR, western blot and confocal microscopy. Our results suggest that EC-LPS challenge induces a decrease in Gluthation-S-Transferase-alpha (GSTA1/A2) mRNA levels, protein expression and catalytic activity; enhanced levels of ROS induced by EC-LPS challenge mediates p65-NF-κB activation and inflammatory response in Caco-2 cells and in CrD colonic mucosa. Furthermore butyrate treatment was seen to restore GSTA1/A2 mRNA levels, protein expression and catalytic activity and to control NF-κB activation, COX-2, ICAM-1 and the release of pro-inflammatory cytokine. In conclusion, butyrate rescues the redox machinery and controls the intracellular ROS balance thus switching off EC-LPS induced inflammatory response in intestinal epithelial cells and in CrD colonic mucosa. PMID:22412931

  17. Bioengineered vocal fold mucosa for voice restoration.

    PubMed

    Ling, Changying; Li, Qiyao; Brown, Matthew E; Kishimoto, Yo; Toya, Yutaka; Devine, Erin E; Choi, Kyeong-Ok; Nishimoto, Kohei; Norman, Ian G; Tsegyal, Tenzin; Jiang, Jack J; Burlingham, William J; Gunasekaran, Sundaram; Smith, Lloyd M; Frey, Brian L; Welham, Nathan V

    2015-11-18

    Patients with voice impairment caused by advanced vocal fold (VF) fibrosis or tissue loss have few treatment options. A transplantable, bioengineered VF mucosa would address the individual and societal costs of voice-related communication loss. Such a tissue must be biomechanically capable of aerodynamic-to-acoustic energy transfer and high-frequency vibration and physiologically capable of maintaining a barrier against the airway lumen. We isolated primary human VF fibroblasts and epithelial cells and cocultured them under organotypic conditions. The resulting engineered mucosae showed morphologic features of native tissue, proteome-level evidence of mucosal morphogenesis and emerging extracellular matrix complexity, and rudimentary barrier function in vitro. When grafted into canine larynges ex vivo, the mucosae generated vibratory behavior and acoustic output that were indistinguishable from those of native VF tissue. When grafted into humanized mice in vivo, the mucosae survived and were well tolerated by the human adaptive immune system. This tissue engineering approach has the potential to restore voice function in patients with otherwise untreatable VF mucosal disease. PMID:26582902

  18. Desmoplastic Melanocytic Nevus of Oral Mucosa.

    PubMed

    Damm, Douglas D; Fowler, Craig B; Schmidt, David P

    2016-09-01

    The desmoplastic melanocytic nevus is an uncommon variant that easily may be confused with a fibrohistiocytic neoplasm or a desmoplastic melanoma. It is believed that the following report describes the first known example of a desmoplastic melanocytic nevus arising in the oral mucosa. The histopathologic and immunohistochemical features that allow separation from other microscopically similar pathoses are stressed. PMID:26747459

  19. Probiotic bacteria reduce salmonella typhimurium intestinal colonization by competing for iron.

    PubMed

    Deriu, Elisa; Liu, Janet Z; Pezeshki, Milad; Edwards, Robert A; Ochoa, Roxanna J; Contreras, Heidi; Libby, Stephen J; Fang, Ferric C; Raffatellu, Manuela

    2013-07-17

    Host inflammation alters the availability of nutrients such as iron to limit microbial growth. However, Salmonella enterica serovar Typhimurium thrives in the inflamed gut by scavenging for iron with siderophores. By administering Escherichia coli strain Nissle 1917, which assimilates iron by similar mechanisms, we show that this nonpathogenic bacterium can outcompete and reduce S. Typhimurium colonization in mouse models of acute colitis and chronic persistent infection. This probiotic activity depends on E. coli Nissle iron acquisition, given that mutants deficient in iron uptake colonize the intestine but do not reduce S. Typhimurium colonization. Additionally, the ability of E. coli Nissle to overcome iron restriction by the host protein lipocalin 2, which counteracts some siderophores, is essential, given that S. Typhimurium is unaffected by E. coli Nissle in lipocalin 2-deficient mice. Thus, iron availability impacts S. Typhimurium growth, and E. coli Nissle reduces S. Typhimurium intestinal colonization by competing for this limiting nutrient. PMID:23870311

  20. Colon distention induces persistent visceral hypersensitivity by mechanotranscription of pain mediators in colonic smooth muscle cells.

    PubMed

    Lin, You-Min; Fu, Yu; Wu, Chester C; Xu, Guang-Yin; Huang, Li-Yen; Shi, Xuan-Zheng

    2015-03-01

    Abdominal pain and distention are major complaints in irritable bowel syndrome. Abdominal distention is mainly attributed to intraluminal retention of gas or solid contents, which may cause mechanical stress to the gut wall. Visceral hypersensitivity (VHS) may account for abdominal pain. We sought to determine whether tonic colon distention causes persistent VHS and if so whether mechanical stress-induced expression (mechanotranscription) of pain mediators in colonic smooth muscle cells (SMCs) plays a role in VHS. Human colonic SMCs were isolated and stretched in vitro to investigate whether mechanical stress upregulates expression of the pain mediator cyclooxygenase-2 (COX-2). Rat colon was distended with a 5-cm-long balloon, and gene expression of COX-2, visceromotor response (VMR), and sensory neuron excitability were determined. Static stretch of colonic SMCs induced marked expression of COX-2 mRNA and protein in a force- and time-dependent manner. Subnoxious tonic distention of the distal colon at ∼30-40 mmHg for 20 or 40 min induced COX-2 expression and PGE2 production in colonic smooth muscle, but not in the mucosa layer. Lumen distention also increased VMR in a force- and time-dependent manner. The increase of VMR persisted for at least 3 days. Patch-clamp experiments showed that the excitability of colon projecting sensory neurons in the dorsal root ganglia was markedly augmented, 24 h after lumen distention. Administration of COX-2 inhibitor NS-398 partially but significantly attenuated distention-induced VHS. In conclusion, tonic lumen distention upregulates expression of COX-2 in colonic SMC, and COX-2 contributes to persistent VHS. PMID:25540231

  1. MicroRNA expression in inflamed and noninflamed gingival tissues from Japanese patients.

    PubMed

    Ogata, Yorimasa; Matsui, Sari; Kato, Ayako; Zhou, Liming; Nakayama, Yohei; Takai, Hideki

    2014-12-01

    Periodontitis is a chronic inflammatory disease caused by specific bacteria and viruses. Local, systemic, and environmental factors affect the rate of disease progression. Immune responses to bacterial products, and the subsequent production of inflammatory cytokines, are crucial in the destruction of periodontal tissue. MicroRNAs (miRNAs) are a class of small RNAs that control various cell processes by negatively regulating protein-coding genes. In this study, we compared miRNA expression in inflamed and noninflamed gingival tissues from Japanese dental patients. Total RNAs were isolated from inflamed and noninflamed gingival tissues. miRNA expression profiles were examined by an miRNA microarray, and the data were analyzed by GeneSpring GX, Ingenuity Pathways Analysis, and the TargetScan databases. Observed miRNA expression levels in inflamed gingiva were confirmed by real-time PCR. The three most overexpressed (by >2.72-fold) miRNAs were hsa-miR-150, hsa-miR-223, and hsa-miR-200b, and the three most underexpressed (by <0.39-fold) miRNAs were hsa-miR-379, hsa-miR-199a-5p, and hsa-miR-214. In IPA analysis, hsa-miR-150, hsa-miR-223, and hsa-miR-200b were associated with inflammatory disease, organismal injury, abnormalities, urological disease, and cancer. The present findings suggest that miRNAs are associated with chronic periodontitis lesions in Japanese. PMID:25500922

  2. Detection of Helicobacter pylori DNA in inflamed dental pulp specimens from Japanese children and adolescents.

    PubMed

    Ogaya, Yuko; Nomura, Ryota; Watanabe, Yoshiyuki; Nakano, Kazuhiko

    2015-01-01

    The oral cavity has been implicated as a source of Helicobacter pylori infection in childhood. Various PCR methods have been used to detect H. pylori DNA in oral specimens with various detection rates reported. Such disparity in detection rates complicates the estimation of the true infection rate of H. pylori in the oral cavity. In the present study, we constructed a novel PCR system for H. pylori detection and used it to analyse oral specimens. Firstly, the nucleotide alignments of genes commonly used for H. pylori detection were compared using the complete genome information for 48 strains registered in the GenBank database. Candidate primer sets with an estimated amplification size of approximately 300-400 bp were selected, and the specificity and sensitivity of the detection system using each primer set were evaluated. Five sets of primers targeting ureA were considered appropriate, of which a single primer set was chosen for inclusion in the PCR system. The sensitivity of the system was considered appropriate and its detection limit established as one to ten cells per reaction. The novel PCR system was used to examine H. pylori distribution in oral specimens (40 inflamed pulp tissues, 40 saliva samples) collected from Japanese children, adolescents and young adults. PCR analysis revealed that the detection rate of H. pylori in inflamed pulp was 15 %, whereas no positive reaction was found in any of the saliva specimens. Taken together, our novel PCR system was found to be reliable for detecting H. pylori. The results obtained showed that H. pylori was detected in inflamed pulp but not saliva specimens, indicating that an infected root canal may be a reservoir for H. pylori. PMID:25332373

  3. Optical detection of (pre-)malignant lesions of the oral mucosa: autofluorescence characteristics of healthy mucosa

    NASA Astrophysics Data System (ADS)

    de Veld, Diana C. G.; Witjes, Max; Roodenburg, Jan L.; Star, Willem M.; Sterenborg, Hericus J. C. M.

    2001-10-01

    Previous clinical results demonstrate the potential of in vivo autofluorescence spectroscopy for early detection of (pre-)malignant lesions of the oral mucosa. For reliable diagnosis, it is necessary to study autofluorescence spectra of healthy mucosa first. We measured excitation-emission maps in healthy subjects and subjects with a history of cancer in the head -neck region. Our results show that different anatomical locations produce distinct autofluorescence spectra. Influences of, among others, smoking and drinking habits require further investigation.

  4. Human colonic goblet cells. Demonstration of distinct subpopulations defined by mucin-specific monoclonal antibodies.

    PubMed Central

    Podolsky, D K; Fournier, D A; Lynch, K E

    1986-01-01

    We studied glycoprotein content of human colonic goblet cells, using a library of monoclonal antibodies (MAbs) directed against purified human colonic mucin (HCM). Using indirect immunofluorescence (IIF), we found that 17 of 23 anti-HCM MAbs stained some or all goblet cells of normal human colonic mucosa. We observed a variety of cellular staining patterns, including (a) diffuse (homogeneous) staining of intracellular mucin, (b) speckled (inhomogeneous) staining of mucin droplets, (c) peripheral staining of intracellular droplets, (d) cytoplasmic staining of goblet cells, and (e) apical (luminal) surface staining. Staining patterns were not associated with particular HCM species. In addition to variable patterns of IIF within individual cells, anti-HCM MAbs varied in the proportion of goblet cells stained. Some MAbs stained all goblet cells, while others stained a limited number of goblet cells. Although each goblet cell contained more than one type mucin, HCM species III, and IV and V appeared to exist in mutually exclusive goblet cell populations and it was possible to define at least seven subpopulations of goblet cells in colonic mucosa by their content of various combinations of HCM species. Anti-HCM MAbs stained goblet cells from other sites within the gastrointestinal tract to a varying extent. Anti-HCM MAbs also showed extensive cross-reactivity with rodent, rabbit, and monkey colonic mucosa. However, several anti-HCM MAbs stained only human colonic mucosa. These data show that human colonic mucosa contains discrete subpopulations of goblet cells that produce distinctive combinations of specific mucin glycoprotein species. Images PMID:2420829

  5. Molecular Genotyping of Anisakis Larvae in Middle Eastern Japan and Endoscopic Evidence for Preferential Penetration of Normal over Atrophic Mucosa

    PubMed Central

    Arai, Toshio; Akao, Nobuaki; Seki, Takenori; Kumagai, Takashi; Ishikawa, Hirofumi; Ohta, Nobuo; Hirata, Nobuto; Nakaji, So; Yamauchi, Kenji; Hirai, Mitsuru; Shiratori, Toshiyasu; Kobayashi, Masayoshi; Fujii, Hiroyuki; Ishii, Eiji; Naito, Mikio; Saitoh, Shin-ichi; Yamaguchi, Toshikazu; Shibata, Nobumitsu; Shimo, Masamune; Tokiwa, Toshihiro

    2014-01-01

    Background Anisakiasis is a parasitic disease caused primarily by Anisakis spp. larvae in Asia and in Western countries. The aim of this study was to investigate the genotype of Anisakis larvae endoscopically removed from Middle Eastern Japanese patients and to determine whether mucosal atrophy affects the risk of penetration in gastric anisakiasis. Methods In this study, 57 larvae collected from 44 patients with anisakiasis (42 gastric and 2 colonic anisakiasis) were analyzed retrospectively. Genotyping was confirmed by restriction fragment length polymorphism (RFLP) analysis of ITS regions and by sequencing the mitochondrial small subunit (SSU) region. In the cases of gastric anisakiasis, correlation analyses were conducted between the frequency of larval penetration in normal/atrophic area and the manifestation of clinical symptoms. Results Nearly all larvae were A. simplex seusu stricto (s.s.) (99%), and one larva displayed a hybrid genotype. The A. simplex larvae penetrated normal mucosa more frequently than atrophic area (p = 0.005). Finally, patients with normal mucosa infection were more likely to exhibit clinical symptoms than those with atrophic mucosa infection (odds ratio, 6.96; 95% confidence interval, 1.52–31.8). Conclusions In Japan, A. simplex s.s. is the main etiological agent of human anisakiasis and tends to penetrate normal gastric mucosa. Careful endoscopic examination of normal gastric mucosa, particularly in the greater curvature of the stomach will improve the detection of Anisakis larvae. PMID:24586583

  6. Exploratory study of oral mucosal colonization of human gastric Helicobacter pylori in mice

    PubMed Central

    Wan, Xueqin; Tang, Dongsheng; Zhang, Xiaohuan; Li, Hongming; Cui, Zhixin; Hu, Sijuan; Huang, Ming

    2014-01-01

    In this study, human gastric Helicobacter pylori (Hp) was closely attached to the pre-treated mouse buccal mucosa by using artificial oral film to induce the growth and colonization of Hp on the buccal mucosa in mice. Sixty BALB/c mice were divided into three groups, in which Hp biofilm colonization was detected in three mice in Hp film group (Hp mesh biofilm accumulation under an optical microscope; Hp accumulated colonization under an electron microscope). There were no Hp biofilms detected in Hp smear group or the control group with black film. In this study, human gastric Hp was first used to artificially induce the growth and colonization of Hp on the buccal mucosa in mice. The mouse model of oral infection with Hp was initially established, providing animal experimental evidences for oral conditions of growth and colonization of Hp on the buccal mucosa in mice, and providing a workable animal modeling method for further research of joint infection of Hp on the mouth and stomach, as well as the relationship between oral Hp and gastric Hp. PMID:24753744

  7. Zinc L-carnosine protects colonic mucosal injury through induction of heat shock protein 72 and suppression of NF-kappaB activation.

    PubMed

    Odashima, Masaru; Otaka, Michiro; Jin, Mario; Wada, Isao; Horikawa, Youhei; Matsuhashi, Tamotsu; Ohba, Reina; Hatakeyama, Natsumi; Oyake, Jinko; Watanabe, Sumio

    2006-11-10

    In this study, we investigated the effects of zinc L-carnosine, an anti-ulcer drug, on acetic acid-induced colonic mucosal injury and the correlation of these effects with expression of 72-kDa heat shock proteins (HSP72) and nuclear factor kappa B (NF-kappaB) activation in rat colonic mucosa in vivo. After intrarectal administration of zinc L-carnosine, the rats received intrarectal infusion of 5% acetic acid (1 ml). The colonic mucosal damage was evaluated by macroscopic assessments 24 h after the intrarectal infusion of acetic acid. Expression of HSP72 in rat colonic mucosa was evaluated by Western blot analysis before and after zinc L-carnosine administration. NF-kappaB activation was evaluated by electrophoretic mobility shift assays (EMSA). Zinc L-carnosine inhibited visible damage in rat colonic mucosa by acetic acid. Expression of HSP72 was significantly increased at 6 h after zinc L-carnosine administration. Furthermore, NF-kappaB activation in colonic mucosa was suppressed 6 h after zinc L-carnosine treatment. These results suggested that zinc L-carnosine protects the colonic mucosa against acetic acid by induction of HSP72 and suppression of NF-kappaB activation and zinc L-carnosine may be a novel therapeutic agent for the therapy of inflammatory bowel disease. PMID:16949620

  8. Monocyte-mediated delivery of polymeric backpacks to inflamed tissues: a generalized strategy to deliver drugs to treat inflammation.

    PubMed

    Anselmo, Aaron C; Gilbert, Jonathan B; Kumar, Sunny; Gupta, Vivek; Cohen, Robert E; Rubner, Michael F; Mitragotri, Samir

    2015-02-10

    Targeted delivery of drugs and imaging agents to inflamed tissues, as in the cases of cancer, Alzheimer's disease, Parkinson's disease, and arthritis, represents one of the major challenges in drug delivery. Monocytes possess a unique ability to target and penetrate into sites of inflammation. Here, we describe a broad approach to take advantage of the natural ability of monocytes to target and deliver flat polymeric particles ("Cellular Backpacks") to inflamed tissues. Cellular backpacks attach strongly to the surface of monocytes but do not undergo phagocytosis due to backpack's size, disk-like shape and flexibility. Following attachment of backpacks, monocytes retain important cellular functions including transmigration through an endothelial monolayer and differentiation into macrophages. In two separate in vivo inflammation models, backpack-laden monocytes exhibit increased targeting to inflamed tissues. Cellular backpacks, and their abilities to attach to monocytes without impairing monocyte functions and 'hitchhike' to a variety of inflamed tissues, offer a new platform for both cell-mediated therapies and broad targeting of inflamed tissues. PMID:25481443

  9. Schistosomiasis manifesting as a colon polyp: a case report

    PubMed Central

    2014-01-01

    Introduction Schistosomiasis is a rare disease with a common intestinal involvement. However, colon polyps associated with Schistosoma in the absence of inflammation have rarely been reported, especially in young people; this is the first case with the following presentation. Case presentation We describe the case of a 20-year-old Ethiopian woman living in Lebanon who presented with nonspecific abdominal symptoms. Her biochemical profile was normal in addition to the results of her stool and urine tests. A colonoscopy showed normal colonic mucosa but surprisingly a large pedunculated polyp was found in her ascending colon. Pathology revealed a hamartomatous polyp but it was full of partially calcified parasitic eggs of Schistosoma mansoni compatible with chronic schistosomiasis. Conclusions She was treated with two doses of praziquantel and showed immediate marked clinical improvement. This unusual case will give us the opportunity to discuss schistosomiasis, its occurrence in colon polyps, clinical significance and the various means of management. PMID:25296942

  10. Do Antimicrobial Peptides and Complement Collaborate in the Intestinal Mucosa?

    PubMed Central

    Kopp, Zoë A.; Jain, Umang; Van Limbergen, Johan; Stadnyk, Andrew W.

    2015-01-01

    It is well understood that multiple antimicrobial peptides (AMPs) are constitutively deployed by the epithelium to bolster the innate defenses along the entire length of the intestines. In addition to this constitutive/homeostatic production, AMPs may be inducible and levels changed during disease. In contrast to this level of knowledge on AMP sources and roles in the intestines, our understanding of the complement cascade in the healthy and diseased intestines is rudimentary. Epithelial cells make many complement proteins and there is compelling evidence that complement becomes activated in the lumen. With the common goal of defending the host against microbes, the opportunities for cross-talk between these two processes is great, both in terms of actions on the target microbes but also on regulating the synthesis and secretion of the alternate family of molecules. This possibility is beginning to become apparent with the finding that colonic epithelial cells possess anaphylatoxin receptors. There still remains much to be learned about the possible points of collaboration between AMPs and complement, for example, whether there is reciprocal control over expression in the intestinal mucosa in homeostasis and restoring the balance following infection and inflammation. PMID:25688244

  11. Nasal Bacterial Colonization in Pediatric Epistaxis: The Role of Topical Antibacterial Treatment

    PubMed Central

    Korkmaz, Mukadder; Çetinkol, Yeliz; Korkmaz, Hakan; Batmaz, Timur

    2016-01-01

    Background: Epistaxis is a common problem in childhood. It has been shown that children with recurrent epistaxis are more likely to have nasal colonization with Staphylococcus aureus. It has been suggested that low-grade inflammation, crusting and increased vascularity due to bacterial colonization contributes to the development of epistaxis in children. Aims: This study aimed to investigate the nasal colonization and treatment outcome in pediatric epistaxis patients. Study Design: Retrospective cross-sectional study. Methods: Charts of the pediatric patients referred to our university hospital otolaryngology outpatient clinics for the evaluation of epistaxis were reviewed. The patients whose nasal cultures had been taken at the first clinical visit comprised the study group. Results: Staphylococcus aureus was the most common bacteria grown. The presence of crusting and hypervascularity was not dependent on the type of bacterial growth and there was no relation between hypervascularity and crusting of the nasal mucosa. Thirty-six patients were evaluated for the outcome analysis. Resolution of bleeding was not dependent on nasal colonization; in patients with colonization, there was no difference between topical antibacterial and non-antibacterial treatments. Conclusion: Despite the high colonization rates, topical antibacterial treatment was not found superior to non-antibacterial treatment. Our study does not support the belief that bacterial colonization results in hypervascularity of the septal mucosa causing epistaxis since no relation was found between nasal colonization, hypervascularity and crusting. The role of bacterial colonization in pediatric epistaxis need to be further investigated and treatment protocols must be determined accordingly. PMID:27403392

  12. Yersinia enterocolitica Affects Intestinal Barrier Function in the Colon.

    PubMed

    Hering, Nina A; Fromm, Anja; Kikhney, Judith; Lee, In-Fah M; Moter, Annette; Schulzke, Jörg D; Bücker, Roland

    2016-04-01

    Infection with Yersinia enterocolitica causes acute diarrhea in early childhood. A mouse infection model presents new findings on pathological mechanisms in the colon. Symptoms involve diarrhea with watery feces and weight loss that have their functional correlates in decreased transepithelial electrical resistance and increased fluorescein permeability. Y. enterocolitica was present within the murine mucosa of both ileum and colon. Here, the bacterial insult was of focal nature and led to changes in tight junction protein expression and architecture. These findings are in concordance with observations from former cell culture studies and suggest a leak flux mechanism of diarrhea. PMID:26621910

  13. Multimodal nonlinear optical microscopy used to discriminate human colon cancer

    NASA Astrophysics Data System (ADS)

    Adur, Javier; Pelegati, Vitor B.; Bianchi, Mariana; de Thomaz, André A.; Baratti, Mariana O.; Carvalho, Hernandes F.; Casco, Víctor H.; Cesar, Carlos L.

    2013-02-01

    Colon cancer is one of the most diffused cancers in the Western World, ranking third worldwide in frequency of incidence after lung and breast cancers. Even if it is curable when detected and treated early, a more accurate premature diagnosis would be a suitable aim for both cancer prognostic and treatment. Combined multimodal nonlinear optical (NLO) microscopies, such as two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third harmonic generation (THG), and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation in colon cancer disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns between normal and malignant human colonic mucosa. Using a set of scoring methods significant differences both in the content, distribution and organization of stroma collagen fibrils, and lifetime components of NADH and FAD cofactors of human colon mucosa biopsies were found. Our results provide a framework for using NLO techniques as a clinical diagnostic tool for human colon cancer, and also suggest that the SHG and FLIM metrics could be applied to other intestinal disorders, which are characterized by abnormal cell proliferation and collagen assembly.

  14. [Inhibition of prostaglandins synthesis in the inflamed site results in opioid-mediated hypoalgesia in rats].

    PubMed

    Huang, Jian; Wu, Jian; Yang, Huai-Zu; Hong, Yanguo

    2016-06-25

    This study was designed to investigate the contribution of prostaglandins to the maintenance of inflammatory pain. Inflammation was induced by intraplantar (i.pl.) injection of carrageenan in right hindpaw in rats. Indomethacin (non-selective COX inhibitor) was administered i.pl. 1 h after the carrageenan injection, and paw withdrawal latency (PWL) responding to noxious heat was measured. β-endorphin (β-END) and μ-opioid receptor (MOR) expressed in the inflamed site were examined by using immunocytochemistry, ELISA and RT-PCR techniques. The results showed that indomethacin dose-dependently increased PWL to the levels that were above the baseline on the day 2 and 3, referred to as hypoalgesia. The hypoalgesia was abolished by a local injection of the non-selective opioid receptor inhibitor naloxone methiodide. The number of β-END-positive cells, the content of β-END and the expression of MOR mRNA in the inflammatory site of inflammation model rats were all significantly increased by indomethacin. These results reveal a novel mechanism of prostaglandins for the inhibition of inflammation-induced endogenous opioid activity. This study provides further evidence that inhibition of prostaglandins in inflamed site could be a promising therapy for inflammatory pain. PMID:27350196

  15. Expression of the Somatostatin Receptor Subtype 4 in Intact and Inflamed Pulmonary Tissues

    PubMed Central

    Varecza, Zoltán; Elekes, Krisztián; László, Terézia; Perkecz, Anikó; Pintér, Erika; Sándor, Zoltán; Szolcsányi, János; Keszthelyi, Dániel; Szabó, Árpád; Sándor, Katalin; Molnár, Tamás F.; Szántó, Zalán; Pongrácz, Judit E.; Helyes, Zsuzsanna

    2009-01-01

    Somatostatin released from capsaicin-sensitive sensory nerves of the lung during endotoxin-induced murine pneumonitis inhibits inflammation and hyperresponsiveness, presumably via somatostatin receptor subtype 4 (sst4). The goal of the present study was to identify sst4 receptors in mouse and human lungs and to reveal its inflammation-induced alterations with real-time quantitative PCR, Western blot, and immunohistochemistry. In non-inflamed mouse and human lungs, mRNA expression and immunolocalization of sst4 are very similar. They are present on bronchial epithelial, vascular endothelial, and smooth-muscle cells. The sst4 receptor protein in the mouse lung significantly increases 24 hr after intranasal endotoxin administration as well as in response to 3 months of whole-body cigarette smoke exposure, owing to the infiltrating sst4-positivite mononuclear cells and neutrophils. In the chronically inflamed human lung, the large number of activated macrophages markedly elevate sst4 mRNA levels, although there is no change in acute purulent pneumonia, in which granulocytes accumulate. Despite mouse granulocytes, human neutrophils do not show sst4 immunopositivity. We provide the first evidence for the expression, localization, and inflammation-induced alterations of sst4 receptors in murine and human lungs. Inasmuch as tissue distribution of this receptor is highly similar, extrapolation of murine experimental results to human conditions might be possible. (J Histochem Cytochem 57:1127–1137, 2009) PMID:19687471

  16. Treatment of non-inflamed obstructive meibomian gland dysfunction by an infrared warm compression device

    PubMed Central

    Goto, E; Monden, Y; Takano, Y; Mori, A; Shimmura, S; Shimazaki, J; Tsubota, K

    2002-01-01

    Aim: To test the short term efficacy and safety of an infrared warm compression device (IWCD, Eye Hot, Cept Co, Tokyo, Japan) as treatment for non-inflamed meibomian gland dysfunction (MGD). Methods: 37 subjects with non-inflamed obstructive MGD, with and without aqueous tear deficiency (ATD) dry eye, participated in a prospective non-comparative interventional case series. Symptom scores, face scores, tear evaporation rates, fluorescein and rose bengal vital staining, tear break up time (BUT), Schirmer test, meibomian gland obstruction, and meibography were compared before and after 2 weeks of therapy. Results: In a total of 37 cases, total subjective symptom scores and subjective face scores improved significantly, from 12.3 (SD 5.9) to 8.4 (6.1), and from 7.0 (1.7) to 5.3 (2.0) (both p <0.0001). The results for tear evaporation rates during forced blinking (p = 0.002), fluorescein staining (p = 0.03), rose bengal staining (p = 0.03), BUT (p <0.0001), and meibomian gland orifice obstruction score (p <0.0001) had also improved significantly at the end of the 2 week period of infrared thermotherapy. No complaints and/or complications of the IWCD were reported. Conclusion: The IWCD was effective and safe for the treatment of MGD. Improved tear stability associated with release of meibum is a possible mechanism of this treatment. PMID:12446375

  17. Tryptophan autofluorescence imaging of neoplasms of the human colon

    NASA Astrophysics Data System (ADS)

    Banerjee, Bhaskar; Renkoski, Timothy; Graves, Logan R.; Rial, Nathaniel S.; Tsikitis, Vassiliki Liana; Nfonsom, Valentine; Pugh, Judith; Tiwari, Piyush; Gavini, Hemanth; Utzinger, Urs

    2012-01-01

    Detection of flat neoplasia is a major challenge in colorectal cancer screening, as missed lesions can lead to the development of an unexpected `incident' cancer prior to the subsequent endoscopy. The use of a tryptophan-related autofluorescence has been reported to be increased in murine intestinal dysplasia. The emission spectra of cells isolated from human adenocarcinoma and normal mucosa of the colon were studied and showed markedly greater emission intensity from cancerous cells compared to cells obtained from the surrounding normal mucosa. A proto-type multispectral imaging system optimized for ultraviolet macroscopic imaging of tissue was used to obtain autofluorescence images of surgical specimens of colonic neoplasms and normal mucosa after resection. Fluorescence images did not display the expected greater emission from the tumor as compared to the normal mucosa, most probably due to increased optical absorption and scattering in the tumors. Increased fluorescence intensity in neoplasms was observed however, once fluorescence images were corrected using reflectance images. Tryptophan fluorescence alone may be useful in differentiating normal and cancerous cells, while in tissues its autofluorescence image divided by green reflectance may be useful in displaying neoplasms.

  18. Buccal mucosa urethroplasty for adult urethral strictures

    PubMed Central

    Zimmerman, W. Britt; Santucci, Richard A.

    2011-01-01

    Urethral strictures are difficult to manage. Some treatment modalities for urethral strictures are fraught with high patient morbidity and stricture recurrence rates; however, an extremely useful tool in the armamentarium of the Reconstructive Urologist is buccal mucosal urethroplasty. We like buccal mucosa grafts because of its excellent short and long-term results, low post-operative complication rate, and relative ease of use. We utilize it for most our bulbar urethral stricture repairs and some pendulous urethral stricture repairs, usually in conjunction with a first-stage Johanson repair. In this report, we discuss multiple surgical techniques for repair of urethral stricture disease. Diagnosis, evaluation of candidacy, surgical techniques, post-operative care, and complications are included. The goal is to raise awareness of buccal mucosa grafting for the management urethral stricture disease. PMID:22022061

  19. Staged buccal mucosa urethroplasty in reoperative hypospadias

    PubMed Central

    Nerli, R. B.; Neelagund, S. E.; Guntaka, Ajay; Patil, Shivagouda; Hiremath, Siddayya C.; Jali, Sujata M.; Vernekar, Ritesh; Hiremath, Murigendra B.

    2011-01-01

    Introduction: Repeated attempts at surgical repair of serious complications involving either the partial or complete breakdown of the hypospadias repair are less likely to succeed because the penis is densely scarred, or significantly shortened, and the skin over the penis is immobile and hypovascular. Buccal mucosa (BM) has become the preferred material for reconstruction, whenever a child with skin-deficient hypospadias needs reoperation. We report the results of our surgical experience with staged reoperation using BM, in the repair of hypospadias in children with complications after multiple failed repairs. Materials and Methods: Children needing reoperation for hypospadias underwent a staged repair using buccal mucosa. The complications were noted. Results: Twenty-one children aged 3 – 16 years underwent this staged repair during the period May 2000 – April 2010. Two of these 21 children had a failed first stage. One child developed a urethro-cutaneous fistula following the second stage, which was corrected in an additional stage. Conclusions: The use of the buccal mucosa graft for urethral reconstruction in a child with hypospadias, needing a reoperation, is a successful method, with a low incidence of complications. PMID:21814309

  20. Human keratinocyte culture from the peritonsillar mucosa.

    PubMed

    Neugebauer, P; Bonnekoh, B; Wevers, A; Michel, O; Mahrle, G; Krieg, T; Stennert, E

    1996-01-01

    Tonsillectomy tissue can be used as a routine source for cultures of oropharyngeal keratinocytes. In so doing, a peritonsillar strip of unaltered mucosa was dissected in the upper submucosa. Subsequent trypsinization yielded 7.0 +/- 3.4 x 10(6) keratinocytes per bilateral tonsillectomy. Keratinocyte attachment and growth in primary culture were promoted by sublethally irradiated 3T3 murine fibroblasts. Three subcultures could be performed without a feeder layer and were characterized by a population doubling time of 4.5 days during log growth phase. Electrophoretic and immunoblot analysis of the third subculture revealed a strong expression of keratin pairs 5/14 and 6/16 as well as keratins 7 and 19, whereas keratins 8/18 were expressed less intensely. The lowest intensity, was found for keratin 13, which is known to be indicative of the differentiated mucosa. The culture technique thus provides an easily available in vitro model for morphological and functional studies on the epithelial compartment of human oropharyngeal mucosa. PMID:8737778

  1. [Bioelectric properties of excised rabbit nasal mucosa].

    PubMed

    Suzumura, E; Takeuchi, K; Sakakura, Y

    1990-06-01

    The water flow across the respiratory epithelia is an important determinant of the efficiency of mucociliary clearance. Bulk water flow has been shown to be coupled to net ion flux. We studied ion transport across rabbit nasal mucosa by measuring bioelectric properties using Ussing chambers. Results were summarized as follows. (1) Compared with tracheal mucosa, nasal mucosa exhibited lower potential difference (p less than 0.01), lower short-circuit current (p less than 0.05), and higher conductance (p less than 0.01). (2) Ouabain 10(-4)M inhibited short-circuit current when added to the submucosal bath of Ussing chambers, and amiloride decreased short-circuit current to about 40% when added to the mucosal bath. (3) When the bubbling of the solution was changed from 95%O2, 5%CO2 to 100%N2, short-circuit current remarkably decreased. (4) A significant positive correlation existed between temperature ranging from 33 degrees C to 41 degrees C and short-circuit current (r = 0.46, p less than 0.02). PMID:2213352

  2. Age and the architecture of oral mucosa.

    PubMed

    Abu Eid, Rasha; Sawair, Faleh; Landini, Gabriel; Saku, Takashi

    2012-06-01

    Age changes affect the oral mucosa (the protective lining of the oral cavity), but few of these have been studied objectively. The aim of this study was to quantitatively analyse a number of morphometric parameters of the ageing oral mucosa. The fractal dimension of the epithelial connective tissue interface (ECTI) was estimated in 42 samples of normal buccal mucosa to correlate any changes in their irregularity to the age of the individuals. Morphometric parameters extracted from theoretical cell areas computed programatically were also analysed. Results showed no significant change in ECTI complexity associated with age; however, there was indication that epithelial cells tended to become larger and flatter with age. Interestingly, while some parameters did not show significant differences case wise, cluster analysis showed that the data clustered the cases into three main age groups: one representing the first two decades of life, another group represents adult life (21-50 years) and the last group representing the ageing population (50-90 years). PMID:21559867

  3. Dopamine receptors in human gastrointestinal mucosa

    SciTech Connect

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

    1987-12-21

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

  4. Spectrally resolved fluorescence imaging of human colonic adenomas.

    PubMed

    Chwirot, B W; Kowalska, M; Sypniewska, N; Michniewicz, Z; Gradziel, M

    1999-06-01

    Native fluorescence (autofluorescence) of human tissues can be a valuable source of diagnostic information for detecting premalignant and malignant lesions in the human body. Digital imaging of autofluorescence may be useful for localization of such lesions during endoscopic examinations. Tissue fluorescence of 31 adenomatous polyps obtained from 16 patients has been excited in vitro using the 325 nm line of a He-Cd laser. Digital images of the autofluorescence are recorded in six spectral bands. This study provides new data about the spatial distributions of autofluorescence intensities emitted in different spectral bands by colonic adenomatous lesions and normal colonic mucosa. Areas characterized by autofluorescence intensity lower than in normal mucosa are found for a majority of the polyps under study. The observed patterns of spatial distribution differ for the different spectral bands and for different polypoid lesions. No inverse correlation is found between the emission intensity and the thickness of colonic mucosa. The results indicate the spectral bands most useful for diagnostic applications and demonstrate the complexity of the optical processes involved in shaping both the spectra and intensities of the autofluorescence. PMID:10515079

  5. Antibiotics conspicuously affect community profiles and richness, but not the density of bacterial cells associated with mucosa in the large and small intestines of mice.

    PubMed

    Puhl, Nathan J; Uwiera, Richard R E; Yanke, L Jay; Selinger, L Brent; Inglis, G Douglas

    2012-02-01

    The influence of three antibiotics (bacitracin, enrofloxacin, and neomycin sulfate) on the mucosa-associated enteric microbiota and the intestines of mice was examined. Antibiotics caused conspicuous enlargement of ceca and an increase in overall length of the intestine. However, there were no pathologic changes associated with increased cecal size or length of the intestine. Conspicuous reductions in the richness of mucosa-associated bacteria and changes to community profiles within the small (duodenum, proximal jejunum, middle jejunum, distal jejunum, and ileum) and large (cecum, ascending colon, and descending colon) intestine occurred in mice administered antibiotics. Communities in antibiotic-treated mice were dominated by a limited number of Clostridium-like (i.e. clostridial cluster XIVa) and Bacteroides species. The richness of mucosa-associated communities within the small and large intestine increased during the 14-day recovery period. However, community profiles within the large intestine did not return to baseline (i.e. relative to the control). Although antibiotic administration greatly reduced bacterial richness, densities of mucosa-associated bacteria were not reduced correspondingly. These data showed that the antibiotics, bacitracin, enrofloxacin, and neomycin sulfate, administered for 21 days to mice did not sterilize the intestine, but did impart a tremendous and prolonged impact on mucosa-associated bacterial communities throughout the small and large intestine. PMID:22185696

  6. Elevated lipopolysaccharide in the colon evokes intestinal inflammation, aggravated in immune modulator-impaired mice.

    PubMed

    Im, Eunok; Riegler, Franz Martin; Pothoulakis, Charalabos; Rhee, Sang Hoon

    2012-08-15

    Frequency of gram-negative bacteria is markedly enhanced in inflamed gut, leading to augmented LPS in the intestine. Although LPS in the intestine is considered harmless and, rather, provides protective effects against epithelial injury, it has been suggested that LPS causes intestinal inflammation, such as necrotizing enterocolitis. Therefore, direct effects of LPS in the intestine remain to be studied. In this study, we examine the effect of LPS in the colon of mice instilled with LPS by rectal enema. We found that augmented LPS on the luminal side of the colon elicited inflammation in the small intestine remotely, not in the colon; this inflammation was characterized by body weight loss, increased fluid secretion, enhanced inflammatory cytokine production, and epithelial damage. In contrast to the inflamed small intestine induced by colonic LPS, the colonic epithelium did not exhibit histological tissue damage or inflammatory lesions, although intracolonic LPS treatment elicited inflammatory cytokine gene expression in the colon tissues. Moreover, we found that intracolonic LPS treatment substantially decreased the frequency of immune-suppressive regulatory T cells (CD4(+)/CD25(+) and CD4(+)/Foxp3(+)). We were intrigued to find that LPS-promoted intestinal inflammation is exacerbated in immune modulator-impaired IL-10(-/-) and Rag-1(-/-) mice. In conclusion, our results provide evidence that elevated LPS in the colon is able to cause intestinal inflammation and, therefore, suggest a physiological explanation for the importance of maintaining the balance between gram-negative and gram-positive bacteria in the intestine to maintain homeostasis in the gut. PMID:22723263

  7. Gene expression profiling of duodenal biopsies discriminates celiac disease mucosa from normal mucosa.

    PubMed

    Bragde, Hanna; Jansson, Ulf; Jarlsfelt, Ingvar; Söderman, Jan

    2011-06-01

    Celiac disease (CD) is identified by histopathologic changes in the small intestine which normalize during a gluten-free diet. The histopathologic assessment of duodenal biopsies is usually routine but can be difficult. This study investigated gene expression profiling as a diagnostic tool. A total of 109 genes were selected to reflect alterations in crypt-villi architecture, inflammatory response, and intestinal permeability and were examined for differential expression in normal mucosa compared with CD mucosa in pediatric patients. Biopsies were classified using discriminant analysis of gene expression. Fifty genes were differentially expressed, of which eight (APOC3, CYP3A4, OCLN, MAD2L1, MKI67, CXCL11, IL17A, and CTLA4) discriminated normal mucosa from CD mucosa without classification errors using leave-one-out cross-validation (n = 39) and identified the degree of mucosal damage. Validation using an independent set of biopsies (n = 27) resulted in four discrepant cases. Biopsies from two of these cases showed a patchy distribution of lesions, indicating that discriminant analysis based on single biopsies failed to identify CD mucosa. In the other two cases, serology support class according to discriminant analysis and histologic specimens were judged suboptimal but assessable. Gene expression profiling shows promise as a diagnostic tool and for follow-up of CD, but further evaluation is needed. PMID:21378598

  8. Red meat and colon cancer: dietary haem, but not fat, has cytotoxic and hyperproliferative effects on rat colonic epithelium.

    PubMed

    Sesink, A L; Termont, D S; Kleibeuker, J H; Van Der Meer, R

    2000-10-01

    High intake of red meat is associated with an increased risk of colon cancer. It has been suggested that fat from red meat is responsible, because high fat intake increases the concentration of cytotoxic lipids in the colon. Experimental studies have not unequivocally supported such a role for fat, however. Recently, we showed that dietary haem, which is abundant in red meat, increased colonic cytotoxicity and epithelial proliferation. In this study, we wanted to clarify whether dietary fat affects colon cancer risk by itself or by modulating the detrimental effects of haem on the colonic epithelium. Rats were fed control or haem-supplemented diets with 10%, 25% or 40% of the energy derived from fat for 14 days. Faeces were collected for biochemical analyses. Colonic cytotoxicity was determined from the degree of lysis of erythrocytes by faecal water. Colonic epithelial proliferation was measured in vivo using [(3)H]thymidine incorporation. Increasing the fat content of the control diets stimulated faecal disposal of both fatty acids and bile acids. It also increased the concentration of fatty acids, but not that of bile acids, in faecal water in control rats. The cytolytic activity of faecal water and colonic epithelial proliferation were unaffected. Dietary haem increased faecal cation content and cytolytic activity of faecal water at all fat levels, suggesting that the colonic mucosa was exposed to high amounts of luminal irritants. This effect was smaller in rats on the low-fat diet. Dietary haem also increased colonic epithelial proliferation at all fat levels. The haem-induced effects were independent of fatty acids or bile acids in the faecal water. In western societies, 30-40% of ingested energy is supplied by dietary fat, so our results suggest that the association between consumption of red meat and risk of colon cancer is mainly due to its haem content, and is largely independent of dietary fat content. PMID:11023550

  9. Characterization and distribution of alpha 2-adrenergic receptors in the human intestinal mucosa.

    PubMed Central

    Valet, P; Senard, J M; Devedjian, J C; Planat, V; Salomon, R; Voisin, T; Drean, G; Couvineau, A; Daviaud, D; Denis, C

    1993-01-01

    The subtype and the expression of the alpha 2-adrenergic receptor were investigated in the normal mucosa from human intestine by means of radioligand binding, RNase mapping, and measurement of adenylate cyclase activity. The study of the binding of the alpha 2-adrenergic antagonist, [3H]RX821002, to epithelial cell membranes indicated the existence of a single class of noninteracting sites displaying a high affinity for the radioligand (Kd = 1.1 +/- 0.5 nM). The rank order of potency of antagonists to inhibit [3H]RX821002 binding (RX821002 > yohimbine = rauwolscine > phentolamine approximately idazoxan >> chlorpromazine > prazosin) suggested that the receptor is of the alpha 2A subtype. A conclusion which is confirmed by the fact that only alpha 2C10 transcripts were found in the human intestine mucosa. Competition curves with (-)-norepinephrine demonstrated that 60% of the receptor population exhibited high affinity for agonists. This high-affinity state was abolished by the addition of GTP plus Na+ or by prior treatment of the membranes with pertussis toxin indicating it corresponded to G protein-coupled receptors. [32P]ADP-ribosylation and immunoblotting experiments identified two pertussis toxin-sensitive G proteins corresponding to Gi2 and Gi3. The study of the distribution of the receptor indicated that (a) the proximal colon is the intestine segment exhibiting the highest receptor density and (b) the receptor is predominantly expressed in crypts and is preferentially located in the basolateral membrane of the polarized cell. The distribution of the receptor along the crypt-surface axis of the colon mucosa can be correlated with a higher level of alpha 2C10-specific mRNA and a higher efficiency of UK14304 to inhibit adenylate cyclase in crypt cells. Images PMID:8098045

  10. Serum vitamin D and colonic vitamin D receptor in inflammatory bowel disease

    PubMed Central

    Abreu-Delgado, Yamilka; Isidro, Raymond A; Torres, Esther A; González, Alexandra; Cruz, Myrella L; Isidro, Angel A; González-Keelan, Carmen I; Medero, Priscilla; Appleyard, Caroline B

    2016-01-01

    AIM: To determine serum vitamin D levels and colonic vitamin D receptor (VDR) expression in inflammatory bowel disease (IBD) and non-IBD patients and correlate these with histopathology. METHODS: Puerto Rican IBD (n = 10) and non-IBD (n = 10) patients ≥ 21 years old scheduled for colonoscopy were recruited. Each patient completed a questionnaire and provided a serum sample and a colonic biopsy of normal-appearing mucosa. For IBD patients, an additional biopsy was collected from visually diseased mucosa. Serum vitamin D levels were measured by ultra-performance liquid chromatography and mass spectrometry. Hematoxylin and eosin stained tissue sections from colonic biopsies were classified histologically as normal or colitis (active/inactive), and scored for the degree of inflammation present (0-3, inactive/absent to severe). Tissue sections from colonic biopsies were also stained by immunohistochemistry for VDR, for which representative diagnostic areas were photographed and scored for staining intensity using a 4-point scale. RESULTS: The IBD cohort was significantly younger (40.40 ± 5.27, P < 0.05) than the non-IBD cohort (56.70 ± 1.64) with a higher prevalence of vitamin D deficiency (40% vs 20%, respectively) and insufficiency (70% vs 50%, respectively). Histologic inflammation was significantly higher in visually diseased mucosa from IBD patients (1.95 ± 0.25) than in normal-appearing mucosa from control patients (0.25 ± 0.08, P < 0.01) and from IBD patients (0.65 ± 0.36, P < 0.05) and correlated inversely with VDR expression in visually diseased colonic tissue from IBD patients (r = -0.44, P < 0.05) and from IBD patients with Crohn’s disease (r = -0.69, P < 0.05), but not in normal-appearing colonic tissue from control patients or IBD patients. Control and IBD patient serum vitamin D levels correlated positively with VDR expression in normal colon from control and IBD patients (r = 0.38, P < 0.05) and with patient age (r = 0.54, P < 0.01). CONCLUSION

  11. Host Immune Defense Peptide LL-37 Activates Caspase-Independent Apoptosis and Suppresses Colon Cancer

    PubMed Central

    Ren, Shun X.; Cheng, Alfred S.L.; To, Ka F.; Tong, Joanna H.M.; Li, May S.; Shen, Jin; Wong, Clover C.M.; Zhang, Lin; Chan, Ruby L.Y.; Wang, Xiao J.; Ng, Simon S.M.; Chiu, Lawrence C.M.; Marquez, Victor E.; Gallo, Richard L.; Chan, Francis K.L.; Yu, Jun; Sung, Joseph J.Y.; Wu, William K.K.; Cho, Chi H.

    2014-01-01

    Cathelicidins are a family of bacteriocidal polypeptides secreted by macrophages and polymorphonuclear leukocytes (PMN). LL-37, the only human cathelicidin, has been implicated in tumorigenesis, but there has been limited investigation of its expression and function in cancer. Here, we report that LL-37 activates a p53-mediated, caspase-independent apoptotic cascade that contributes to suppression of colon cancer. LL-37 was expressed strongly in normal colon mucosa but downregulated in colon cancer tissues, where in both settings its expression correlated with terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling-positive apoptotic cells. Exposure of colon cancer cells to LL-37 induced phosphatidylserine externalization and DNA fragmentation in a manner independent of caspase activation. Apoptogenic function was mediated by nuclear translocation of the proapoptotic factors, apoptosis-inducing factor (AIF) and endonuclease G (EndoG), through p53-dependent upregulation of Bax and Bak and downregulation of Bcl-2 via a pertussis toxin–sensitive G-protein–coupled receptor (GPCR) pathway. Correspondingly, colonic mucosa of cathelicidin-deficient mice exhibited reduced expression of p53, Bax, and Bak and increased expression of Bcl-2 together with a lower basal level of apoptosis. Cathelicidin-deficient mice exhibited an increased susceptibility to azoxymethane-induced colon tumorigenesis, establishing pathophysiologic relevance in colon cancer. Collectively, our findings show that LL-37 activates a GPCR-p53-Bax/Bak/Bcl-2 signaling cascade that triggers AIF/EndoG–mediated apoptosis in colon cancer cells. PMID:23100468

  12. Liver Colonization Competence Governs Colon Cancer Metastasis

    NASA Astrophysics Data System (ADS)

    Kuo, Tsong-Hong; Kubota, Tetsuro; Watanabe, Masahiko; Furukawa, Toshiharu; Teramoto, Tatuso; Ishibiki, Kyuya; Kitajima, Masaki; Rahim Moosa, A.; Penman, Sheldon; Hoffman, Robert M.

    1995-12-01

    Tumors that metastasize do so to preferred target organs. To explain this apparent specificity, Paget, >100 years ago, formulated his seed and soil hypothesis; i.e., the cells from a given tumor would "seed" only favorable "soil" offered by certain organs. The hypothesis implies that cancer cells must find a suitable "soil" in a target organ-i.e., one that supports colonization-for metastasis to occur. We demonstrate in this report that ability of human colon cancer cells to colonize liver tissue governs whether a particular colon cancer is metastatic. In the model used in this study, human colon tumors are transplanted into the nude mouse colon as intact tissue blocks by surgical orthotopic implantation. These implanted tumors closely simulate the metastatic behavior of the original human patient tumor and are clearly metastatic or nonmetastatic to the liver. Both classes of tumors were equally invasive locally into tissues and blood vessels. However, the cells from each class of tumor behave very differently when directly injected into nude mouse livers. Only cells from metastasizing tumors are competent to colonize after direct intrahepatic injection. Also, tissue blocks from metastatic tumors affixed directly to the liver resulted in colonization, whereas no colonization resulted from nonmetastatic tumor tissue blocks even though some growth occurred within the tissue block itself. Thus, local invasion (injection) and even adhesion to the metastatic target organ (blocks) are not sufficient for metastasis. The results suggest that the ability to colonize the liver is the governing step in the metastasis of human colon cancer.

  13. Optical properties of human colon tissues in the 350 - 2500 nm spectral range

    NASA Astrophysics Data System (ADS)

    Bashkatov, A. N.; Genina, E. A.; Kochubey, V. I.; Rubtsov, V. S.; Kolesnikova, E. A.; Tuchin, V. V.

    2014-08-01

    We present the optical characteristics of the mucosa and submucosa of human colon tissue. The experiments are performed in vitro using a LAMBDA 950 spectrophotometer in the 350 - 2500 nm spectral range. The absorption and scattering coefficients and the scattering anisotropy factor are calculated based on the measured diffuse reflectance and total and collimated transmittance spectra using the inverse Monte Carlo method.

  14. X-ray tube with a graphite field emitter inflamed at high temperature

    PubMed Central

    Iwai, Yusuke; Koike, Takayoshi; Hayama, Youhei; Jouzuka, Atsuo; Nakamura, Tomonori; Onizuka, Yoshihiro; Miyoshi, Motosuke; Mimura, Hidenori

    2013-01-01

    The authors developed a class of novel graphite-based field emitters, known as graphite field emitters inflamed at high temperature (GFEIHTs), which includes numerous edges and juts. The GFEIHT field emission characteristics are investigated in a vacuum tube (10−7 Pa), and an anode current exceeding 2 mA is obtained. The authors also fabricated tipped-off x-ray tubes using GFEIHTs. No degradation in the anode current is observed under the operating conditions of 16.6 kV anode voltage and 160 μA anode current. The current dispersion, defined as the standard deviation (σ)/mean over 24 h, is 2.8%. The authors successfully demonstrated radiography and x-ray fluorescence spectrometry using an x-ray tube with GFEIHT. PMID:23847750

  15. Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue.

    PubMed

    Binder, Waltraud; Mousa, Shaaban A; Sitte, Nicolle; Kaiser, Myriam; Stein, Christoph; Schäfer, Michael

    2004-07-01

    Stress induces analgesia by mechanisms within and outside the brain. Here we show that the sympathetic nervous system is an essential trigger of intrinsic opioid analgesia within peripheral injured tissue. Noradrenaline, injected directly into inflamed hind paws of male Wistar rats, produced dose-dependent antinociception, reversible by alpha(1)-, alpha(2)- and beta(2)-antagonists. alpha(1)-, alpha(2)- and beta(2)-adrenergic receptors were demonstrated on beta-endorphin-containing immune cells and noradrenaline induced adrenergic receptor-specific release of beta-endorphin from immune cell suspensions. This antinociceptive effect of noradrenaline was reversed by micro - and delta-opioid antagonists as well as by anti-beta-endorphin. Stress-induced peripheral analgesia was abolished by chemical sympathectomy and by adrenergic antagonists. These findings indicate that sympathetic neuron-derived noradrenaline stimulates adrenergic receptors on inflammatory cells to release beta-endorphin, which induces analgesia via activation of peripheral opioid receptors. PMID:15245482

  16. [THE MYCOBIOTA OF TUNICA MUCOSA OF MOUTH AND SURFACE OF REMOVABLE ACRYLIC LAMINAR DENTAL PROSTHESES UNDER ORTHOPEDIC REHABILITATION].

    PubMed

    Chesnokov, V A; Chesnokova, M G; Stafeiev, A A; Mironov, A Yu

    2016-02-01

    The analysis was carried out to detect mycobiota of tunica mucosa of mouth and surface of dental prostheses under orthopedic rehabilitation using removable acrylic laminar dental prostheses. The inoculation of biosamples received from examined patients permitted to isolate Candida albicans. The C. albicans from tunica mucosa of mouth of patients before prosthetics inoculated in low concentration making up 0.33±0.23 CFU/ml in comparison with concentration of 1.92±0.53 CFU/ml after prosthetics. The highest content of C. albicans was marked in biosample from surface of dental prostheses in comparison with biotope of tunica mucosa of mouth of patients. The concentration of microbiota from surface of dental prostheses signicantly surpassed the same on tunica mucosa of mouth of patients prior prosthetics. In patients with removable acrylic laminar dental prostheses under orthopedic rehabilitation various spectrum of representatives of microbiota was detected From biosamples from surface of dentalprostheses of patients the most frequently were inoculated such representatives of gram-positive microbiota as S. aureus, Micrococcus spp., S.haemolyticus, and of gram-negative microbiota Klebsiella pneumonae, Pseudomonas aeruginosa. The cultural analysis of biosamples from patients with removable acrylic laminar dental prostheses detected Candida albicans on tunica mucosa of mouth before and after prosthetics as well as on surfaces of prostheses. The highest concentration of C.albicans is established in case of colonization of removable acrylic laminar dental prostheses. The received data testifies possible involvement of fungi capable of expressed potential ofpathogenicity, in development and maintenance of inflammatory process of tunica mucosa of mouth under orthopedic rehabilitation using removable acrylic laminar dental prostheses. PMID:27455570

  17. Activity-dependent hyperpolarization of EGABA is absent in cutaneous DRG neurons from inflamed rats

    PubMed Central

    Zhu, Yi; Zhang, Xiu-Lin; Gold, Michael S.

    2013-01-01

    A shift in GABAA signaling from inhibition to excitation in primary afferent neurons appears to contribute to the inflammation-induced increase in afferent input to the central nervous system (CNS). An activity-dependent depolarization of the GABA equilibrium potential (EGABA) has been described in CNS neurons which drives a shift in GABAA signaling from inhibition to excitation. The purpose of the present study was to determine if such an activity-dependent depolarization of EGABA occurs in primary afferents and whether the depolarization is amplified with persistent inflammation. Acutely dissociated retrogradely labeled cutaneous DRG neurons from naïve and inflamed rats were studied with gramicidin perforated patch recording. Rather than a depolarization, 200 action potentials delivered at 2 Hz resulted in a ~10 mV hyperpolarization of EGABA in cutaneous neurons from naïve rats. No such hyperpolarization was observed in neurons from inflamed rats. The shift in EGABA was not blocked by 10 µM bumetanide. Furthermore, because activity-dependent hyperpolarization of EGABA was fully manifest in the absence of HCO3− in the bath solution, this shift was not dependent on a change in HCO3−-Cl− exchanger activity, despite evidence of HCO3−-Cl− exchangers in DRG neurons that may contribute to the establishment of EGABA in the presence of HCO3−. While the mechanism underlying the activity-dependent hyperpolarization of EGABA has yet to be identified, because this mechanism appears to function as a form of feedback inhibition, facilitating GABA mediated inhibition of afferent activity, it may serve as a novel target for the treatment of inflammatory pain. PMID:24135545

  18. Conjugation to polyethylene glycol polymer promotes aptamer biodistribution to healthy and inflamed tissues.

    PubMed

    Boomer, Ryan M; Lewis, Scott D; Healy, Judith M; Kurz, Markus; Wilson, Charles; McCauley, Thomas G

    2005-01-01

    Here, we examine biodistribution of radiolabeled aptamers and assess the relative ability of different stabilized aptamer compositions (mixed 2'-F/2'-O-Me; fully 2'-O-Me modified) to access inflamed tissues in a murine inflammation model. Biodistribution of 3H-labeled aptamers, including pegylated and unpegylated compositions, was assessed 3 hours postadministration using quantitative whole body autoradiography (QWBA). Aptamer penetration of cells in kidney and liver was also examined at a qualitative level by microautoradiography. To evaluate aptamer distribution to diseased tissues, inflammation was induced locally in animal hind limbs by treatment with carrageenan just prior to aptamer dosing. Aptamer compositions examined exhibited significant variation in distribution levels among organs and tissues. Highest concentrations of radioactivity in whole body tissues for all animals were observed in the kidney and urinary bladder contents. Relatively little radioactivity was associated with brain, spinal cord, and adipose tissue. Overall, the total level of radioactivity in whole body tissues was significantly higher for a 20-kDa PEG conjugate than for other aptamers. Comparatively high levels of the 20-kDa conjugate were seen in well-perfused organs and tissues, including liver, lungs, spleen, bone marrow, and myocardium. A fully 2'-O-Me composition aptamer had the lowest level of radioactivity in whole body tissues but distributed to higher concentrations in the gastrointestinal tract contents relative to other aptamers. Interestingly, the 20-kDa PEG-conjugated aptamer showed significantly higher levels of distribution to inflamed paw tissues than did either unconjugated or fully 2'-O-Me-modified aptamers. PMID:16201906

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

    PubMed Central

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

    2016-01-01

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

  20. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    SciTech Connect

    Zhang, Xufang; Jiang, Hongwei; Gong, Qimei; Fan, Chen; Huang, Yihua; Ling, Junqi

    2014-08-08

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration.

  1. Colon diverticula - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100158.htm Colon diverticula - series To use the sharing features on ... 6 out of 6 Normal anatomy Overview The colon, or large intestine, is a muscular tube that ...

  2. Colon cancer - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100157.htm Colon cancer - Series To use the sharing features on ... 5 out of 5 Normal anatomy Overview The colon, or large intestine, is a muscular tube that ...

  3. Cruciferous vegetables and glutathione: their effects on colon mucosal glutathione level and colon tumor development in rats induced by DMH.

    PubMed

    Chen, M F; Chen, L T; Boyce, H W

    1995-01-01

    The effect of a diet containing 10-40% lyophilized cabbage or broccoli as cruciferous vegetable or 10-40% lyophilized potato as noncruciferous vegetable fed for 14 days on the colon mucosal glutathione (GSH) level was studied in male rats. The GSH levels of the duodenum mucosa and the liver were also measured. Cabbage and broccoli enhanced the colon and duodenum mucosal GSH levels in a dose-related manner; potato had no effect. All three vegetables had no effect on the liver GSH level. The effect of GSH on colon tumorigenesis induced by 1,2-dimethylhydrazine (DMH) was also examined in rats. Male Sprague-Dawley rats were injected with DMH (20 mg/kg body wt) weekly for 20 weeks. DMH lowered the colon mucosal GSH level. GSH (100 mg/day/rat) dissolved in the drinking water and given to rats during and after DMH injections had little or no effect on tumor incidence and total number of colon tumors. Tumors were larger in rats that received GSH than in those that received water. This study shows that the colon mucosal GSH level can be enhanced by feeding rats a diet high in cabbage or broccoli and that GSH added to the drinking water did not affect DMH-induced colon tumorigenesis under the experimental conditions used. PMID:7739917

  4. Colon cancer - Series (image)

    MedlinePlus

    Colon cancer is the third most common cancer in the United States. Risk factors include a diet low ... The treatment of colon cancer depends on the stage of the disease. Stage I cancer is limited to the inner lining of the colon; ...

  5. Honey and Apoptosis in Human Gastric Mucosa

    PubMed Central

    Ghaffari, Aida; Somi, Mohammad H; Safaiyan, Abdolrasoul; Modaresi, Jabiz; Ostadrahimi, Alireza

    2012-01-01

    Background: Gastric cancer is the fourth most common malignancy in the world. Honey is a complex mixture of special biological active constituents. Honey possesses antioxidant and antitumor properties. Nutritional studies have indicated that consumption of honey modulates the risk of developing gastric cancer. On the other hand, apoptosis has been reported to play a decisive role in precancerous changes. Our chief study was conducted to assess the relationship between consumption of honey and apoptosis in human gastric mucosa. Method: This cross-sectional study was conducted on 98 subjects over 18 years old, referred to two hospitals in Tabriz, Iran. Subjects were undergone an upper gastrointestinal endoscopy, 62 subjects were finally enrolled. Honey consumption was assessed by a Food Frequency Questionnaire (FFQ) and apoptosis was detected by TUNEL technique. We tested polynomial curve to find the best fit between honey consumption and apoptosis. Results: A positive relation between honey consumption and apoptosis was found (P=0.024). Our results indicated that the final and the best fit curve was: apoptosis = 1.714+1.648(honey amount) - 0.533(honey amount)2 +1.833×10-5(honey amount)7. Conclusion: Honey consumption had positive effects on gastric cancer by inducing apoptosis in gastric mucosa. PMID:24688918

  6. Novel diet-related mouse model of colon cancer parallels human colon cancer

    PubMed Central

    Prasad, Anil R; Prasad, Shilpa; Nguyen, Huy; Facista, Alexander; Lewis, Cristy; Zaitlin, Beryl; Bernstein, Harris; Bernstein, Carol

    2014-01-01

    AIM: To investigate the close parallels between our novel diet-related mouse model of colon cancer and human colon cancer. METHODS: Twenty-two wild-type female mice (ages 6-8 wk) were fed the standard control diet (AIN-93G) and an additional 22 female mice (ages 6-8 wk) were fed the control diet supplemented with 0.2% deoxycholic acid [diet + deoxycholic acid (DOC)] for 10 mo. Tumors occurred in the colons of mice fed diet + DOC and showed progression to colon cancer [adenocarcinoma (AC)]. This progression is through the stages of tubular adenoma (TA), TA with high grade dysplasia or adenoma with sessile serrated morphology, intramucosal AC, AC stage T1, and AC stage T2. The mouse tumors were compared to human tumors at the same stages by histopathological analysis. Sections of the small and large intestines of mice and humans were evaluated for glandular architecture, cellular and nuclear morphology including cellular orientation, cellular and nuclear atypia, pleomorphism, mitotic activity, frequency of goblet cells, crypt architecture, ulceration, penetration of crypts through the muscularis mucosa and presence of malignant crypts in the muscularis propria. In addition, preserved colonic tissues from genetically similar male mice, obtained from a prior experiment, were analyzed by immunohistochemistry. The male mice had been fed the control diet or diet + DOC. Four molecular markers were evaluated: 8-OH-dG, DNA repair protein ERCC1, autophagy protein beclin-1 and the nuclear location of beta-catenin in the stem cell region of crypts. Also, male mice fed diet + DOC plus 0.007% chlorogenic acid (diet + DOC + CGA) were evaluated for ERCC1, beclin-1 and nuclear location of beta-catenin. RESULTS: Humans with high levels of diet-related DOC in their colons are at a substantially increased risk of developing colon cancer. The mice fed diet + DOC had levels of DOC in their colons comparable to that of humans on a high fat diet. The 22 mice without added DOC in their diet

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

    PubMed

    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. PMID:27622368

  8. Dietary fibre and colon cancer: epidemiologic and experimental evidence.

    PubMed Central

    Reddy, B S

    1980-01-01

    Epidemiologic studies have identified two dietary factors, a relatively high intake of fat and a relatively low intake of fibre, that are associated with colon cancer in humans. However, a recent study has shown a low risk of large bowel cancer in a rural Finnish population with a high dietary intake of fat, but also a high intake of fibre. Observations in humans and studies in animals have indicated that dietary fibre may protect against colon carcinogenesis by binding bile acids in the intestinal tract, by a direct effect on the colonic mucosa and by an indirect effect on the metabolism of carcinogens. The strength of protection varies with the type of fibre. PMID:6254626

  9. [Colonic microbial biocenosis in rheumatoid arthritis].

    PubMed

    Gul'neva, M Iu; Noskov, S M

    2011-01-01

    The aim of the work was to study colonic microbial biocenosis and colonizing ability of opportunistic bacteria in 32 patients with rheumatoid arthritis (RA) and 30 healthy subjects. RA was diagnosed based on the American Rheumatism Association criteria (1987). Qualitative and quantitative composition of the microflora was detected by a bacteriological method. StatSoft Statistics 6.0 was used to treat the data obtained. RA was associated with significant modification of the intestinal flora, viz. decrease in lactobacteria and significant increase of enterococci, clostridia, colibacteria showing reduced enzymatic activity, and opportunistic species. Also, symbiotic relationships between microorganisms altered. The fraction of bifidobacteria, bacteroids, and lactopositive colibacteria reduced while the abundance of opportunistic enterobacteria and staphylococci was elevated. Opportunistic Enterobacteriaceae were present in urine and nasal mucosa which suggested their translocation from the intestines. It is concluded that changes in intestinal microflora and colonization by opportunistic bacteria enhance the risk of development of co-morbid conditions in patients with RA. PMID:21932563

  10. Detection of colonic polyp candidates with level set-based thickness mapping over the colon wall

    NASA Astrophysics Data System (ADS)

    Han, Hao; Li, Lihong; Duan, Chaijie; Zhao, Yang; Wang, Huafeng; Liang, Zhengrong

    2015-03-01

    Further improvement of computer-aided detection (CADe) of colonic polyps is vital to advance computed tomographic colonography (CTC) toward a screening modality, where the detection of flat polyps is especially challenging because limited image features can be extracted from flat polyps, and the traditional geometric features-based CADe methods usually fail to detect such polyps. In this paper, we present a novel pipeline to automatically detect initial polyp candidates (IPCs), especially flat polyps, from CTC images. First, the colon wall mucosa was extracted via a partial volume segmentation approach as a volumetric layer, where the inner border of colon wall can be obtained by shrinking the volumetric layer using level set based adaptive convolution. Then the outer border of colon wall (or the colon wall serosa) was segmented via a combined implementation of geodesic active contour and Mumford-Shah functional in a coarse-to-fine manner. Finally, the wall thickness was estimated along a unique path between the segmented inner and outer borders with consideration of the volumetric layers and was mapped onto a patient-specific three-dimensional (3D) colon wall model. The IPC detection results can usually be better visualized in a 2D image flattened from the 3D model, where abnormalities were detected by Z-score transformation of the thickness values. The proposed IPC detection approach was validated on 11 patients with 22 CTC scans, and each scan has at least one flat poly annotation. The above presented novel pipeline was effective to detect some flat polyps that were missed by our CADe system while keeping false detections in a relative low level. This preliminary study indicates that the presented pipeline can be incorporated into an existing CADe system to enhance the polyp detection power, especially for flat polyps.

  11. Identification of Helicobacter spp. in oral secretions vs. gastric mucosa of stray cats.

    PubMed

    Shojaee Tabrizi, A; Jamshidi, Sh; Oghalaei, A; Zahraei Salehi, T; Bayati Eshkaftaki, A; Mohammadi, M

    2010-01-01

    The definite mode of transmission of Helicobacter infection is largely unknown. This study was carried out primarily, to determine the existence of Helicobacter spp. in the oral secretions of stray cats as one of the possible routes of transmission and secondly, to evaluate the accordance between oral and gastric colonization of Helicobacter spp. in these cats. Forty-three adult stray cats were thus studied for the presence of Helicobacter species by quantitative rapid urease test (RUT), cytology and PCR. Helicobacter spp. were found in the oral secretions and gastric biopsies of 93% and 67.5% of the stray cats, respectively. There was not, however, any agreement observed between Helicobacter colonization at these two locations, at neither genus nor species level. These findings suggest that the oral cavity is routinely exposed to transient forms of bacteria and may temporarily harbor Helicobacter spp. Thus, oral cavity as a source of Helicobacter spp. may act as a reservoir for transmission and may not necessarily reflect the colonization status of the gastric mucosa. PMID:19726141

  12. Mucosa-Associated Bacterial Microbiome of the Gastrointestinal Tract of Weaned Pigs and Dynamics Linked to Dietary Calcium-Phosphorus

    PubMed Central

    Mann, Evelyne; Schmitz-Esser, Stephan; Zebeli, Qendrim; Wagner, Martin; Ritzmann, Mathias; Metzler-Zebeli, Barbara U.

    2014-01-01

    Dietary composition largely influences pig’s gastrointestinal microbiota and represents a useful prophylactic tool against enteric disturbances in young pigs. Despite the importance for host-microbe interactions and bacterial colonization, dietary responses of the mucosa-associated bacterial communities are less well investigated. In the present study, we characterized the mucosa-associated bacterial communities at the Pars non-glandularis of the stomach, ileum and colon, and identified shifts in these communities in response to different dietary calcium-phosphorus (Ca-P) contents (100% versus 190% of the Ca and P requirements) in combination with two basal diets (wheat-barley- or corn-based) in weaned pigs. Pyrosequencing of 16S rRNA genes from 93 mucosal samples yielded 447,849 sequences, clustering into 997 operational taxonomic units (OTUs) at 97% similarity level. OTUs were assigned to 198 genera belonging to 14 different phyla. Correlation-based networks revealed strong interactions among OTUs at the various gastrointestinal sites. Our data describe a previously not reported high diversity and species richness at the Pars non-glandularis of the stomach in weaned pigs. Moreover, high versus adequate Ca-P content significantly promoted Lactobacillus by 14.9% units (1.4 fold change) at the gastric Pars non-glandularis (P = 0.035). Discriminant analysis revealed dynamic changes in OTU composition in response to dietary cereals and Ca-P contents at all gastrointestinal sites which were less distinguishable at higher taxonomic levels. Overall, this study revealed a distinct mucosa-associated bacterial community at the different gut sites, and a strong effect of high Ca-P diets on the gastric community, thereby markedly expanding our comprehension on mucosa-associated microbiota and their diet-related dynamics in weaned pigs. PMID:24466298

  13. Primary colorectal lymphoma comprising both components of diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma combined with cytomegalovirus colitis.

    PubMed

    Katsumata, Ryo; Matsumoto, Hiroshi; Motoyasu, Osawa; Murao, Takahisa; Ishii, Manabu; Fujita, Minoru; Tokunaga, Hirotoshi; Akiyama, Takashi; Wada, Hideho; Sugihara, Takashi; Shiotani, Akiko; Haruma, Ken

    2016-04-01

    A 16-year-old girl presented to our hospital with diarrhea and abdominal pain. The macroscopic findings of colonoscopy revealed multiple submucosal tumors and multiple ulcers, which were localized in the sigmoid colon, and diffuse granular mucosa which extended to the total colon. The pathological diagnosis was malignant lymphoma comprising both components of diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma, because the large lymphoma cells were CD20+, CD10-, and CD5-. Furthermore, immunohistochemical analysis of colorectal biopsy samples from multiple ulcers revealed cytomegalovirus (CMV)-positive cells. The patient was diagnosed with primary colorectal lymphoma comprising both components of DLBCL and MALT lymphoma combined with CMV colitis. She received anti-viral medication and chemotherapy. PMID:27015999

  14. Antinociceptive effects induced through the stimulation of spinal cannabinoid type 2 receptors in chronically inflamed mice.

    PubMed

    Curto-Reyes, Verdad; Boto, Tamara; Hidalgo, Agustín; Menéndez, Luis; Baamonde, Ana

    2011-10-01

    The stimulation of spinal cannabinoid type 2 (CB(2)) receptors is a suitable strategy for the alleviation of experimental pain symptoms. Several reports have described the up-regulation of spinal cannabinoid CB(2) receptors in neuropathic settings together with the analgesic effects derived from their activation. Besides, we have recently reported in two murine bone cancer models that the intrathecal administration of cannabinoid CB(2) receptor agonists completely abolishes hyperalgesia and allodynia, whereas spinal cannabinoid CB(2) receptor expression remains unaltered. The present experiments were designed to measure the expression of spinal cannabinoid CB(2) receptors as well as the analgesic efficacy derived from their stimulation in mice chronically inflamed by the intraplantar injection of complete Freund's adjuvant 1 week before. Both spinal cannabinoid CB(2) receptors mRNA measured by real-time PCR and cannabinoid CB(2) receptor protein levels measured by western blot remained unaltered in inflamed mice. Besides, the intrathecal (i.t.) administration of the cannabinoid CB(2) receptor agonists AM1241, (R,S)-3-(2-Iodo-5-nitrobenzoyl)-1-(1-methyl-2-piperidinylmethyl)-1H-indole, (0.03-1 μg) and JWH 133, (6aR,10aR)-3-(1,1-Dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran, (3-30 μg) dose-dependently blocked inflammatory thermal hyperalgesia and mechanical allodynia. The analgesic effects induced by both agonists were counteracted by the coadministration of the selective cannabinoid CB(2) receptor antagonist SR144528, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide, (5 μg) but not by the cannabinoid CB(1) receptor antagonist AM251, N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide, (10 μg). The effects induced by AM1241 were also inhibited by the coadministration of the opioid receptor antagonist, naloxone

  15. Products used on female genital mucosa.

    PubMed

    Farage, Miranda A; Lennon, Lisa; Ajayi, Funmi

    2011-01-01

    A wide variety of products are used by women in the genital area and, therefore, come into contact with the genital mucosa. The largest category of such products would be those used for cleanliness and odor control, such as soaps and body washes, douches, premoistened wipes and towelettes, dusting powder and deodorant sprays. A second large category of products are those intended to absorb fluids, such as products used for menstrual protection (tampons, pads and panty liners) and incontinence protection. Lubricants and moisturizers, and aesthetic products (hair removal products and dyes) are also fairly common. In addition, over the counter medications are now available for the treatment of fungal infections. This chapter briefly discusses the products women use on or around the genital area, the perceived or real benefits, and the potential health effects of these products. PMID:21325843

  16. Epithelioid leiomyoma of the oral mucosa.

    PubMed

    Koutlas, I G; Manivel, J C

    1996-12-01

    Oral leiomyomas are rare because of the paucity of smooth muscle in the mouth. The solid and vascular types are the most frequent variants. The purpose of this article is to present the pathologic features and differential diagnosis of an example of epithelioid leiomyoma. A 50-year-old woman presented with a small raised nonpainful polypoid lesion of unknown duration on the right buccal mucosa. The tumor was well demarcated and consisted of large epithelioid cells with distinct cytoplasmic borders, round to oval nuclei, and prominent nucleoli. A few mitoses (4 in 20 high power fields) were present. Scattered spindle cells were also seen. The cytoplasm was eosinophilic to amphophilic and showed frequent clearing and retraction. Small capillaries were identified and surrounded by neoplastic cells that gave the lesion an angiomyomatous appearance. Masson trichrome stain highlighted focally smooth muscle cells. Immunohistochemical evaluation revealed staining for vimentin, desmin, and muscle-specific actim. PMID:8974140

  17. [Pigmented lesions of the genital mucosa].

    PubMed

    Hengge, U R; Meurer, M

    2005-06-01

    Pigmented lesions of the genital mucosa are more frequent in women than in men. They represent a spectrum of different benign entities. A biopsy is always recommended when the diagnosis cannot be made with certainty on clinical examination and dermatoscopy. Differential diagnostic considerations include melanocytic nevi, blue nevi and syndromes featuring lentigines. Malignant melanomas of the penis and vulva are uncommon tumors which usually appear in elderly patients. They frequently present as painless palpable nodules at routine examination. The treatment consists of excision with histological control of the margins. An aggressive surgical approach has not been shown to prolong the poor 5-year survival. Cooperation with gynecologists and urologists is essential for the optimal management of such patients. PMID:15905972

  18. Morphological characteristics of the canine and feline stomach mucosa.

    PubMed

    Zahariev, P; Sapundzhiev, E; Pupaki, D; Rashev, P; Palov, A; Todorov, T

    2010-12-01

    The stomach mucosa structure in animals belonging to Order Carnivora indicates some specific characteristics in comparison with the other mammals. Between the bases of the mucosal glands and the lamina muscularis mucosae there is an additional plate which most of the morphologists have defined as lamina subglandularis. In currently used Nomina histologica this layer is indicated as stratum compactum in carnivorous stomach mucosa. The investigation aims were to study and compare canine and feline stomach tunica mucosa characteristics as well as to measure the thickness of stratum compactum and to specify some of the certain collagen types and fibronectin compounds. Conventional and differential histological and ultrastructural methods and immuno-histochemical approaches for investigation of the canine and feline stomach samples were used. The specific organization of the carnivorous stomach wall arrangement was established. In the structure of the canine stomach mucosa, no evidence of stratum compactum was observed. The presence of stratum compactum in feline stomach mucosa was ascertained and measured. Using an immunohistochemical method very high expression of collagen type IV and fibronectin, moderate positive reaction of collagen type III, and a comparatively weakest expression of collagen types I and V in the structure of stratum compactum from cat stomach mucosa was shown. The obtained results clarify the characteristics of the stomach mucosa morphology and could be used as a basis for distinguishing the stomach wall structure of the animal species belonging to Canidae and Felidae families although they are both carnivores. PMID:20825386

  19. Urethral mucosa prolapse in an 18-year-old adolescent.

    PubMed

    Olumide, Akadiri; Kayode Olusegun, Ajenifuja; Babatola, Bakare

    2013-01-01

    Urethra mucosa prolapse is a benign condition in which there is a circular protrusion of the distal urethra through the external urethra meatus. It is more commonly seen in prepubertal black girls and postmenopausal white women. It is rare in the reproductive age group. This case describes the presentation and management of an 18-year-old adolescent with urethra mucosa prolapse. PMID:24109533

  20. Lichenoid reaction to carbamazepine in the oral mucosa: case report.

    PubMed

    Artico, Gabriela; Bruno, Ingrid S; Seo, Juliana; Hirota, Silvio K; Acay, Renata; Migliari, Dante A

    2011-01-01

    Lichenoid drug reactions are more common in skin, but they may also occur in the oral mucosa. It is difficult to diagnose these lesions due to their clinical similarity to the idiopathic oral lichen planus lesions. The present article reports a case of lichenoid reaction in oral mucosa associated to the use of carbamazepine, emphasizing the diagnostic process. PMID:22068798

  1. Up-regulation of CNDP2 facilitates the proliferation of colon cancer

    PubMed Central

    2014-01-01

    Background Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis. Methods We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena. Results The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E. Conclusions Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo. PMID:24885395

  2. Mouth and Genital Ulcers with Inflamed Cartilage Syndrome: Case Report and Review of the Published Work

    PubMed Central

    Kaneko, Yuka; Nakai, Noriaki; Kida, Takashi; Kawahito, Yutaka; Katoh, Norito

    2016-01-01

    Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome are disease that fulfilled criteria for diagnosis of Behcet's disease (BD) and relapsing polychondritis (RP). We report a 22-year-old Japanese woman presented with MAGIC syndrome and we described the clinicopathological characteristics of MAGIC syndrome based on a review of published cases from July 1985 to December 2015. In our case, the patient with oral aphthae, erythema nodosum, acne-like eruptions, uveitis, and polyarthritis fulfilled criteria for diagnosis of incomplete form of BD. The patient with uveitis, polyarthritis, and histological confirmation of chondritis also fulfilled criteria for diagnosis of RP. The patient was successfully treated with oral colchicine followed by prednisolone. The symptoms of MAGIC syndrome gradually disappeared, and the prednisolone dosage was gradually decreased and stopped. She has been in remission without active medication for a further 8 months. In the previous reports, some authors suggested that MAGIC syndrome was not a disease entity and might be RP occurring secondary to BD, another association of an autoimmune disease, or vasculitis with RP. However, the pathogenic association between MAGIC syndrome, BD, and RP is still unclear, and the number of reported cases of MAGIC syndrome is insufficient to establish a clear explanation. Therefore, further accumulation of data and careful observation of the clinical course are required to improve the understanding of MAGIC syndrome. PMID:27293269

  3. Specific transfection of inflamed brain by macrophages: a new therapeutic strategy for neurodegenerative diseases.

    PubMed

    Haney, Matthew J; Zhao, Yuling; Harrison, Emily B; Mahajan, Vivek; Ahmed, Shaheen; He, Zhijian; Suresh, Poornima; Hingtgen, Shawn D; Klyachko, Natalia L; Mosley, R Lee; Gendelman, Howard E; Kabanov, Alexander V; Batrakova, Elena V

    2013-01-01

    The ability to precisely upregulate genes in inflamed brain holds great therapeutic promise. Here we report a novel class of vectors, genetically modified macrophages that carry reporter and therapeutic genes to neural cells. Systemic administration of macrophages transfected ex vivo with a plasmid DNA (pDNA) encoding a potent antioxidant enzyme, catalase, produced month-long expression levels of catalase in the brain resulting in three-fold reductions in inflammation and complete neuroprotection in mouse models of Parkinson's disease (PD). This resulted in significant improvements in motor functions in PD mice. Mechanistic studies revealed that transfected macrophages secreted extracellular vesicles, exosomes, packed with catalase genetic material, pDNA and mRNA, active catalase, and NF-κb, a transcription factor involved in the encoded gene expression. Exosomes efficiently transfer their contents to contiguous neurons resulting in de novo protein synthesis in target cells. Thus, genetically modified macrophages serve as a highly efficient system for reproduction, packaging, and targeted gene and drug delivery to treat inflammatory and neurodegenerative disorders. PMID:23620794

  4. From morphology to biochemical state - intravital multiphoton fluorescence lifetime imaging of inflamed human skin.

    PubMed

    Huck, Volker; Gorzelanny, Christian; Thomas, Kai; Getova, Valentina; Niemeyer, Verena; Zens, Katharina; Unnerstall, Tim R; Feger, Julia S; Fallah, Mohammad A; Metze, Dieter; Ständer, Sonja; Luger, Thomas A; Koenig, Karsten; Mess, Christian; Schneider, Stefan W

    2016-01-01

    The application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of inflammatory skin diseases. In the present study, we combined multiphoton-based intravital tomography (MPT) and fluorescence lifetime imaging (MPT-FLIM) within the scope of a clinical trial of atopic dermatitis with the aim of providing personalised data on the aetiopathology of inflammation in a non-invasive manner at patients' bedsides. These 'optical biopsies' generated via MPT were morphologically analysed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Two independent morphometric algorithms reliably showed an even distribution in healthy skin and a perinuclear accumulation in inflamed skin. Moreover, using MPT-FLIM, detection of the onset and progression of inflammatory processes could be achieved. In conclusion, the change in the distribution of mitochondria upon inflammation and the verification of an altered cellular metabolism facilitate a better understanding of inflammatory skin diseases and may permit early diagnosis and therapy. PMID:27004454

  5. Comparative Ability of Mesenchymal Stromal Cells from Different Tissues to Limit Neutrophil Recruitment to Inflamed Endothelium

    PubMed Central

    Munir, Hafsa; Luu, Nguyet-Thin; Clarke, Lewis S. C.; Nash, Gerard B.; McGettrick, Helen M.

    2016-01-01

    Mesenchymal stromal cells (MSC) are tissue-resident stromal cells capable of modulating immune responses, including leukocyte recruitment by endothelial cells (EC). However, the comparative potency of MSC from different sources in suppressing recruitment, and the necessity for close contact with endothelium remain uncertain, although these factors have implications for use of MSC in therapy. We thus compared the effects of MSC isolated from bone marrow, Wharton’s jelly, and trabecular bone on neutrophil recruitment to cytokine-stimulated EC, using co-culture models with different degrees of proximity between MSC and EC. All types of MSC suppressed neutrophil adhesion to inflamed endothelium but not neutrophil transmigration, whether directly incorporated into endothelial monolayers or separated from them by thin micropore filters. Further increase in the separation of the two cell types tended to reduce efficacy, although this diminution was least for the bone marrow MSC. Immuno-protective effects of MSC were also diminished with repeated passage; with BMMSC, but not WJMSC, completing losing their suppressive effect by passage 7. Conditioned media from all co-cultures suppressed neutrophil recruitment, and IL-6 was identified as a common bioactive mediator. These results suggest endogenous MSC have a homeostatic role in limiting inflammatory leukocyte infiltration in a range of tissues. Since released soluble mediators might have effects locally or remotely, infusion of MSC into blood or direct injection into target organs might be efficacious, but in either case, cross-talk between EC and MSC appears necessary. PMID:27171357

  6. Resveratrol suppresses PAI-1 gene expression in a human in vitro model of inflamed adipose tissue.

    PubMed

    Zagotta, Ivana; Dimova, Elitsa Y; Funcke, Jan-Bernd; Wabitsch, Martin; Kietzmann, Thomas; Fischer-Posovszky, Pamela

    2013-01-01

    Increased plasminogen activator inhibitor-1 (PAI-1) levels are associated with a number of pathophysiological complications; among them is obesity. Resveratrol was proposed to improve obesity-related health problems, but the effect of resveratrol on PAI-1 gene expression in obesity is not completely understood. In this study, we used SGBS adipocytes and a model of human adipose tissue inflammation to examine the effects of resveratrol on the production of PAI-1. Treatment of SGBS adipocytes with resveratrol reduced PAI-1 mRNA and protein in a time- and concentration-dependent manner. Further experiments showed that obesity-associated inflammatory conditions lead to the upregulation of PAI-1 gene expression which was antagonized by resveratrol. Although signaling via PI3K, Sirt1, AMPK, ROS, and Nrf2 appeared to play a significant role in the modulation of PAI-1 gene expression under noninflammatory conditions, those signaling components were not involved in mediating the resveratrol effects on PAI-1 production under inflammatory conditions. Instead, we demonstrate that the resveratrol effects on PAI-1 induction under inflammatory conditions were mediated via inhibition of the NF κ B pathway. Together, resveratrol can act as NF κ B inhibitor in adipocytes and thus the subsequently reduced PAI-1 expression in inflamed adipose tissue might provide a new insight towards novel treatment options of obesity. PMID:23819014

  7. Orf virus IL-10 reduces monocyte, dendritic cell and mast cell recruitment to inflamed skin.

    PubMed

    Bennett, Jared R; Lateef, Zabeen; Fleming, Stephen B; Mercer, Andrew A; Wise, Lyn M

    2016-02-01

    Orf virus (ORFV) is a zoonotic parapoxvirus that causes pustular dermatitis of sheep, and occasionally humans. Despite causing sustained infections, ORFV induces only a transient increase in pro-inflammatory signalling and the trafficking of innate immune cells within the skin seems to be impaired. An explanation for this tempered response to ORFV infection may lie in its expression of a homolog of the anti-inflammatory cytokine, interleukin (IL)-10. Using a murine model in which inflammation was induced by bacterial lipopolysaccharide, we examined the effects of the ORFV-IL-10 protein on immune cell trafficking to and from the skin. ORFV-IL-10 limited the recruitment of blood-derived Gr-1(int)/CD11b(int) monocytes, CD11c(+ve)/MHC-II(+ve) dendritic cells and c-kit(+ve)/FcεR1(+ve) mature mast cells into inflamed skin. ORFV-IL-10 also suppressed the activation of CD11c(+ve)/MHC-II(+ve) dendritic cells within the skin, reducing their trafficking to the draining lymph node. These findings suggest that expression of IL-10 by ORFV may contribute to the impaired trafficking of innate immune cells within infected skin. PMID:26732486

  8. Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways

    PubMed Central

    Tränkner, Dimitri; Hahne, Nadeau; Sugino, Ken; Hoon, Mark A.; Zuker, Charles

    2014-01-01

    Asthma is a common debilitating inflammatory lung disease affecting over 200 million people worldwide. Here, we investigated neurogenic components involved in asthmatic-like attacks using the ovalbumin-sensitized murine model of the disease, and identified a specific population of neurons that are required for airway hyperreactivity. We show that ablating or genetically silencing these neurons abolished the hyperreactive broncho-constrictions, even in the presence of a fully developed lung inflammatory immune response. These neurons are found in the vagal ganglia and are characterized by the expression of the transient receptor potential vanilloid 1 (TRPV1) ion channel. However, the TRPV1 channel itself is not required for the asthmatic-like hyperreactive airway response. We also demonstrate that optogenetic stimulation of this population of TRP-expressing cells with channelrhodopsin dramatically exacerbates airway hyperreactivity of inflamed airways. Notably, these cells express the sphingosine-1-phosphate receptor 3 (S1PR3), and stimulation with a S1PR3 agonist efficiently induced broncho-constrictions, even in the absence of ovalbumin sensitization and inflammation. Our results show that the airway hyperreactivity phenotype can be physiologically dissociated from the immune component, and provide a platform for devising therapeutic approaches to asthma that target these pathways separately. PMID:25049382

  9. Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways.

    PubMed

    Tränkner, Dimitri; Hahne, Nadeau; Sugino, Ken; Hoon, Mark A; Zuker, Charles

    2014-08-01

    Asthma is a common debilitating inflammatory lung disease affecting over 200 million people worldwide. Here, we investigated neurogenic components involved in asthmatic-like attacks using the ovalbumin-sensitized murine model of the disease, and identified a specific population of neurons that are required for airway hyperreactivity. We show that ablating or genetically silencing these neurons abolished the hyperreactive broncho-constrictions, even in the presence of a fully developed lung inflammatory immune response. These neurons are found in the vagal ganglia and are characterized by the expression of the transient receptor potential vanilloid 1 (TRPV1) ion channel. However, the TRPV1 channel itself is not required for the asthmatic-like hyperreactive airway response. We also demonstrate that optogenetic stimulation of this population of TRP-expressing cells with channelrhodopsin dramatically exacerbates airway hyperreactivity of inflamed airways. Notably, these cells express the sphingosine-1-phosphate receptor 3 (S1PR3), and stimulation with a S1PR3 agonist efficiently induced broncho-constrictions, even in the absence of ovalbumin sensitization and inflammation. Our results show that the airway hyperreactivity phenotype can be physiologically dissociated from the immune component, and provide a platform for devising therapeutic approaches to asthma that target these pathways separately. PMID:25049382

  10. Gastrointestinal endocannabinoid system: multifaceted roles in the healthy and inflamed intestine.

    PubMed

    Smid, Scott D

    2008-11-01

    1. The endogenous cannabinoid (endocannabinoid) system is emerging as a key modulator of intestinal physiology, influencing motility, secretion, epithelial integrity and immune function in the gut, in addition to influencing satiety and emesis. 2. Accumulating evidence suggests that the endocannabinoid system may play a pivotal role in the pathophysiology of gastrointestinal disease, particularly in the light of recent studies demonstrating an effect of endocannabinoids on the development of experimental inflammation and linkages with functional clinical disorders characterized by altered motility. 3. The predominant endocannabinoids, anandamide and 2-arachidonoylglycerol, not only mediate their effects via two recognized cannabinoid receptor subtypes, namely CB(1) and CB(2), but emerging evidence now shows they are also substrates for cyclo-oxygenase (COX)-2, generating a distinct and novel class of prostaglandin ethanolamides (prostamides) and prostaglandin glycerol esters. These compounds are bioactive and may mediate an array of biological effects distinct to those of conventional prostanoids. 4. The effects of prostamides on gastrointestinal motility, secretion, sensation and immune function have not been characterized extensively. Prostamides may play an important role in gastrointestinal inflammation, particularly given the enhanced expression of both COX-2 and endocannabinoids that occurs in the inflamed gut. 5. Further preclinical studies are needed to determine the therapeutic potential of drugs targeting the endocannabinoid system in functional and inflammatory gut disorders, to assist with the determination of feasibility for clinical translation. PMID:18671715

  11. Mouth and Genital Ulcers with Inflamed Cartilage Syndrome: Case Report and Review of the Published Work.

    PubMed

    Kaneko, Yuka; Nakai, Noriaki; Kida, Takashi; Kawahito, Yutaka; Katoh, Norito

    2016-01-01

    Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome are disease that fulfilled criteria for diagnosis of Behcet's disease (BD) and relapsing polychondritis (RP). We report a 22-year-old Japanese woman presented with MAGIC syndrome and we described the clinicopathological characteristics of MAGIC syndrome based on a review of published cases from July 1985 to December 2015. In our case, the patient with oral aphthae, erythema nodosum, acne-like eruptions, uveitis, and polyarthritis fulfilled criteria for diagnosis of incomplete form of BD. The patient with uveitis, polyarthritis, and histological confirmation of chondritis also fulfilled criteria for diagnosis of RP. The patient was successfully treated with oral colchicine followed by prednisolone. The symptoms of MAGIC syndrome gradually disappeared, and the prednisolone dosage was gradually decreased and stopped. She has been in remission without active medication for a further 8 months. In the previous reports, some authors suggested that MAGIC syndrome was not a disease entity and might be RP occurring secondary to BD, another association of an autoimmune disease, or vasculitis with RP. However, the pathogenic association between MAGIC syndrome, BD, and RP is still unclear, and the number of reported cases of MAGIC syndrome is insufficient to establish a clear explanation. Therefore, further accumulation of data and careful observation of the clinical course are required to improve the understanding of MAGIC syndrome. PMID:27293269

  12. High endothelial-like venules in chronically inflamed periodontal tissues exchange polymorphs.

    PubMed

    Zoellner, H F; Hunter, N

    1989-12-01

    A survey of 58 gingival biopsies revealed the presence of periodontal high endothelial-like venules (PHELVs) in chronically inflamed gingival tissues. PHELVs were found to exchange polymorphonuclear cells (PMNs) almost exclusively in advanced periodontitis, with PMNs greatly exceeding the number of mononuclear cells found in PHELVs (P less than 0.001). Electron microscopy confirmed the emigration of PMNs from these vessels. The enzyme histochemical and ultrastructural features as well as the 35SO4 uptake properties of PHELVs were similar to those of the well-characterized high endothelial venules (HEVs) of rat lymph nodes. It is generally accepted that HEVs in lymphoid tissues and inflammatory sites are specially adapted to assist in the emigration of lymphocytes. However, the observation of preferential PMN emigration in the apparent absence of lymphocyte exchange from PHELVs compels further investigation of other possible functions for HEVs. In relation to this, endothelial cells are capable of producing potent cytokines and inflammatory mediators which may contribute to the development of lesions, and the possibility is discussed that high endothelial cells are functionally adapted to enhance the production of such factors. PMID:2614574

  13. The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung

    PubMed Central

    Kaur, Manminder; Bell, Thomas J; Fujino, Naoya; Cook, Peter C; Svedberg, Freya R; MacDonald, Andrew S; Maciewicz, Rose A; Singh, Dave; Hussell, Tracy

    2014-01-01

    Much of the biology surrounding macrophage functional specificity has arisen through examining inflammation-induced polarising signals, but this also occurs in homeostasis, requiring tissue-specific environmental triggers that influence macrophage phenotype and function. The TAM receptor family of receptor tyrosine kinases (Tyro3, Axl and MerTK) mediates the non-inflammatory removal of apoptotic cells by phagocytes through the bridging phosphatidylserine-binding molecules Gas6 or Protein S. We show that one such TAM receptor (Axl) is exclusively expressed on mouse airway macrophages, but not interstitial macrophages and other lung leukocytes, under homeostatic conditions and is constitutively ligated to Gas6. Axl expression is potently induced by GM-CSF expressed in the healthy and inflamed airway, and by type I interferon or TLR3 stimulation on human and mouse macrophages, indicating potential involvement of Axl in apoptotic cell removal under inflammatory conditions. Indeed, an absence of Axl does not cause sterile inflammation in health, but leads to exaggerated lung inflammatory disease upon influenza infection. These data imply that Axl allows specific identification of airway macrophages, and that its expression is critical for macrophage functional compartmentalisation in the airspaces or lung interstitium. We propose that this may be a critical feature to prevent excessive inflammation due to secondary necrosis of apoptotic cells that have not been cleared by efferocytosis. PMID:25603826

  14. Specific Transfection of Inflamed Brain by Macrophages: A New Therapeutic Strategy for Neurodegenerative Diseases

    PubMed Central

    Haney, Matthew J.; Zhao, Yuling; Harrison, Emily B.; Mahajan, Vivek; Ahmed, Shaheen; He, Zhijian; Suresh, Poornima; Hingtgen, Shawn D.; Klyachko, Natalia L.; Mosley, R. Lee; Gendelman, Howard E.; Kabanov, Alexander V.; Batrakova, Elena V.

    2013-01-01

    The ability to precisely upregulate genes in inflamed brain holds great therapeutic promise. Here we report a novel class of vectors, genetically modified macrophages that carry reporter and therapeutic genes to neural cells. Systemic administration of macrophages transfected ex vivo with a plasmid DNA (pDNA) encoding a potent antioxidant enzyme, catalase, produced month-long expression levels of catalase in the brain resulting in three-fold reductions in inflammation and complete neuroprotection in mouse models of Parkinson's disease (PD). This resulted in significant improvements in motor functions in PD mice. Mechanistic studies revealed that transfected macrophages secreted extracellular vesicles, exosomes, packed with catalase genetic material, pDNA and mRNA, active catalase, and NF-κb, a transcription factor involved in the encoded gene expression. Exosomes efficiently transfer their contents to contiguous neurons resulting in de novo protein synthesis in target cells. Thus, genetically modified macrophages serve as a highly efficient system for reproduction, packaging, and targeted gene and drug delivery to treat inflammatory and neurodegenerative disorders. PMID:23620794

  15. Quantitative and phenotypic analysis of bone marrow-derived cells in the intact and inflamed central nervous system

    PubMed Central

    Litwak, Sara

    2011-01-01

    Bone marrow has been proposed as a possible source of cells capable of replacing injured neural cells in diseases such as Multiple Sclerosis (MS). Previous studies have reported conflicting results regarding the transformation of bone marrow cells into neural cells in vivo. This study is a detailed analysis of the fate of bone marrow derived cells (BMDC) in the CNS of C57Bl/6 mice with and without experimental autoimmune encephalomyelitis using flow cytometry to identify GFP-labeled BMDC that lacked the pan-hematopoietic marker CD45 and co-expressed neural markers polysialic acid-neural cell adhesion molecule or A2B5. A small number of BMDC displaying neural markers and lacking CD45 expression was identified within both the non-inflamed and inflamed CNS. However, the majority of BMDC exhibited a hematopoietic phenotype. PMID:21975545

  16. Elevated IL-23R Expression and Foxp3+Rorgt+ Cells in Intestinal Mucosa During Acute and Chronic Colitis.

    PubMed

    Yang, Jiayin; Xu, Lili

    2016-01-01

    BACKGROUND IL-23/IL-23R signaling plays a pivotal role during the course of inflammatory bowel diseases (IBD). However, the underlying mechanisms are poorly characterized. Foxp3+ regulatory T cells are critical in the maintenance of gut immune homeostasis and therefore are important in preventing the development of IBD. This study was performed to clarify the association between IL-23/IL-23R signaling and Foxp3+ regulatory T cells in colitis. MATERIAL AND METHODS Acute and chronic mouse colitis models were established by administering mice DSS in drinking water. IL-23R, IL-23, IL-I7, and IFN-γ expression level, as well as regulatory T cell, Th17-, and Th1-related transcription factors Foxp3, RORgt, and T-bet were assayed by real-time PCR. The frequency of Foxp3+ RORγt+ cells in a Foxp3+ cell population in colon mucosa during acute and chronic colitis was evaluated through flow cytometry. The signaling pathway mediated by IL-23R in the colon mucosa from acute colitis mice and chronic colitis mice was monitored by Western blot analysis. RESULTS We detected elevated IL-23R, IL-23, and IFN-γ expression in colon mucosa during acute and chronic colitis and found increased IL-17 in acute colitis mice. Transcription factors Foxp3 and T-bet were elevated in colon mucosa during acute and chronic colitis. Phosphorylation of Stat3 was greatly enhanced, indicating the activation of IL-23R function in colitis mice. The percentage of Foxp3+ T cells in acute and chronic colitis mice was comparable to control mice, but there was a 2-fold increase of Foxp3+ RORγt+ cells among the Foxp3+ cell population in acute and chronic colitis mice compared to control mice. CONCLUSIONS These findings indicate that the induction of Foxp3+ RORgt+ T cells could be enhanced during inflammation in the intestine where IL-23R expression is greatly induced. Our study highlights the importance of IL-23R expression level and the instability of Foxp3+ regulatory T cells in the development of

  17. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    SciTech Connect

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei; Lu, Su; Tang, Huamei; Peng, Zhihai

    2014-06-27

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation.

  18. Short chain fatty acids and colon cancer.

    PubMed

    Augenlicht, Leonard H; Mariadason, John M; Wilson, Andrew; Arango, Diego; Yang, WanCai; Heerdt, Barbara G; Velcich, Anna

    2002-12-01

    The development of intestinal cancer involves complex genetic and epigenetic alterations in the intestinal mucosa. The principal signaling pathway responsible for the initiation of tumor formation, the APC-beta-catenin-TCF4 pathway, regulates both cell proliferation and colonic cell differentiation, but many other intrinsic and extrinsic signals also modulate these cell maturation pathways. The challenge is to understand how signaling and cell maturation are also modulated by nutritional agents. Through gene expression profiling, we have gained insight into the mechanisms by which short chain fatty acids regulate these pathways and the differences in response of gene programs, and of the specific regulation of the c-myc gene, to physiological regulators of intestinal cell maturation, such as butyrate, compared with pharmacological regulators such as the nonsteroidal antiinflammatory drug sulindac. Moreover, we used a combination of gene expression profiling of the response of cells in culture to sulindac and the response of the human mucosa in subjects treated with sulindac for 1 month, coupled with a mouse genetic model approach, to identify the cyclin dependent kinase inhibitor p21(WAF1/Cip1) as an important suppressor of Apc-initiated intestinal tumor formation and a necessary component for tumor inhibition by sulindac. Finally, the mucous barrier, secreted by intestinal goblet cells, is the interface between the luminal contents and the intestinal mucosa. We generated a mouse genetic model with a targeted inactivation of the Muc2 gene that encodes the major intestinal mucin. These mice have no recognizable goblet cells due to the failure of cells to synthesize and store mucin. This leads to perturbations in intestinal crypt architecture, increased cellular proliferation and rates of cell migration, decreased apoptosis and development of adenomas and adenocarcinomas in the small and large intestine and the rectum. PMID:12468628

  19. Ornithine transcarbamylase and disaccharidase activities in damaged intestinal mucosa of children--diagnosis of hereditary ornithine transcarbamylase deficiency in mucosa.

    PubMed

    Cathelineau, L; Briand, P; Rabier, D; Navarro, J

    1985-12-01

    Ornithine transcarbamylase (OTC) and disaccharidase activities were measured in the intestinal mucosa from 182 children. Sixty-nine had normal mucosa, whereas the others had different degrees of mucosal damage. Brush border disaccharidases are significantly decreased in all degrees of villous atrophy. In contrast, OTC is not affected in moderate atrophy and only slightly decreased in severe atrophy. Consequently, the OTC-to-lactase ratio increases with the degree of atrophy and permits discrimination between normal and damaged mucosa. The assay of OTC activity in intestinal mucosa for the diagnosis of hereditary deficiency in male hemizygote patients generally provides nonambiguously low results, whereas in heterozygote females the amount of residual activity is in the range of the results found in damaged mucosa. PMID:4067786

  20. Lymphocyte binding to vascular endothelium in inflamed skin revisited: a central role for vascular adhesion protein-1 (VAP-1).

    PubMed

    Arvilommi, A M; Salmi, M; Kalimo, K; Jalkanen, S

    1996-04-01

    The binding of leukocytes to vascular endothelium and their migration into tissues is mediated by adhesion molecules on the endothelial cells and leukocytes. Vascular adhesion protein-1 (VAP-1) is a 170-180/90-kDa endothelial molecule expressed most prominently in high endothelial venules in peripheral lymph node (PLN) type lymphatic tissues. VAP-1 mediates lymphocyte binding to PLN, tonsil and synovium. The expression of VAP-1 is induced in inflammatory diseases such as arthritis and gut inflammation. We examined the expression, structure and function of VAP-1 in normal and inflamed skin and compared it to those of other adhesion molecules implicated in skin homing. In psoriasis lichen ruber planus, pemphigoid and allergic lesions, VAP-1 was markedly upregulated. The expression of VAP-1 was also increased in biopsies of healthy skin of the patients. The VAP-1 molecule induced in skin is decorated with abundant sialic acids. VAP-1 inflamed skin is functional, since inhibition with anti-VAP-1 monoclonal antibodies caused a 60% reduction in lymphocytes adhesion to vascular endothelium. Antibodies against E-selectin, which has been regarded as the major vascular addressin directing cutaneous lymphocyte traffic, and, surprisingly, against peripheral lymph node addressin (PNAd), caused inhibitions of 30% and 60%, respectively, in the frozen section adhesion assay. These findings suggest important roles also for VAP-1 and PNAd in lymphocyte homing into inflamed skin. PMID:8625974

  1. Glucocorticoids differentially regulate Na-bile acid cotransport in normal and chronically inflamed rabbit ileal villus cells.

    PubMed

    Coon, Steven; Kekuda, Ramesh; Saha, Prosenjit; Sundaram, Uma

    2010-05-01

    Previous studies have demonstrated that apical Na-bile acid cotransport (ASBT) is inhibited during chronic ileitis by both a decrease in the affinity as well as a decrease in the number of cotransporters. Methylprednisolone (MP), a commonly used treatment for inflammatory bowel disease (IBD, e.g., Crohn's disease), has been shown to reverse the inhibition of several other Na-solute cotransporters during chronic enteritis. However, the effect of MP on ASBT in the chronically inflamed ileum is not known. MP stimulated ASBT in villus cells from the normal rabbit ileum by increasing the cotransporter expression without a change in the affinity of the cotransporter for bile acid. Western blot studies demonstrated an increase in cotransporter expression. MP reversed the inhibition of ASBT in villus cells from the chronically inflamed ileum. Kinetic studies demonstrated that the mechanism of MP-mediated reversal of ASBT inhibition was secondary to a restoration of both affinity as well as cotransporter numbers. Western blot analysis demonstrated restoration of cotransporter numbers after MP treatment of rabbits with chronic ileitis. Thus MP stimulates ASBT in the normal ileum by increasing cotransporter numbers. MP reverses the inhibition of ASBT during chronic ileitis. However, MP restores the diminished affinity as well as cotransporter expression levels during chronic ileitis. Thus MP differentially regulates ASBT in the normal and in the chronically inflamed ileum. PMID:20075140

  2. Glucocorticoids differentially regulate Na-bile acid cotransport in normal and chronically inflamed rabbit ileal villus cells

    PubMed Central

    Coon, Steven; Kekuda, Ramesh; Saha, Prosenjit

    2010-01-01

    Previous studies have demonstrated that apical Na-bile acid cotransport (ASBT) is inhibited during chronic ileitis by both a decrease in the affinity as well as a decrease in the number of cotransporters. Methylprednisolone (MP), a commonly used treatment for inflammatory bowel disease (IBD, e.g., Crohn's disease), has been shown to reverse the inhibition of several other Na-solute cotransporters during chronic enteritis. However, the effect of MP on ASBT in the chronically inflamed ileum is not known. MP stimulated ASBT in villus cells from the normal rabbit ileum by increasing the cotransporter expression without a change in the affinity of the cotransporter for bile acid. Western blot studies demonstrated an increase in cotransporter expression. MP reversed the inhibition of ASBT in villus cells from the chronically inflamed ileum. Kinetic studies demonstrated that the mechanism of MP-mediated reversal of ASBT inhibition was secondary to a restoration of both affinity as well as cotransporter numbers. Western blot analysis demonstrated restoration of cotransporter numbers after MP treatment of rabbits with chronic ileitis. Thus MP stimulates ASBT in the normal ileum by increasing cotransporter numbers. MP reverses the inhibition of ASBT during chronic ileitis. However, MP restores the diminished affinity as well as cotransporter expression levels during chronic ileitis. Thus MP differentially regulates ASBT in the normal and in the chronically inflamed ileum. PMID:20075140

  3. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells.

    PubMed

    Zhang, Xufang; Jiang, Hongwei; Gong, Qimei; Fan, Chen; Huang, Yihua; Ling, Junqi

    2014-08-01

    High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration. PMID:25019990

  4. Prevention of leukocyte migration to inflamed skin with a novel fluorosugar modifier of cutaneous lymphocyte-associated antigen.

    PubMed

    Dimitroff, Charles J; Kupper, Thomas S; Sackstein, Robert

    2003-10-01

    E-selectin and P-selectin on dermal postcapillary venules play critical roles in the migration of effector T cells into inflamed skin. P-selectin glycoprotein ligand-1 (PSGL-1) modified by alpha1,3-fucosyltransferase is the principal selectin ligand on skin-homing T cells and is required for effector T cell entry into inflamed skin. We have previously shown that a fluorinated analog of N-acetylglucosamine peracetylated-4-fluorinated-d-glucosamine (4-F-GlcNAc), inhibits selectin ligand expression on human T cell PSGL-1. To analyze 4-F-GlcNAc efficacy in dampening effector T cell migration to inflamed skin, we elicited allergic contact hypersensitivity (CHS) reactions in mice treated with 4-F-GlcNAc. We also investigated 4-F-GlcNAc efficacy on lymphocyte E-selectin ligand expression in LNs draining antigen-sensitized skin and on other immunological processes requisite for CHS responses. Our results showed that 4-F-GlcNAc treatment attenuated lymphocyte E-selectin ligand expression in skin-draining LNs and prevented CHS reactions. Significant reductions in inflammatory lymphocytic infiltrate were observed, while pathways related to antigenic processing and presentation and naive T cell recognition within skin-draining LNs were unaffected. These data indicate that 4-F-GlcNAc prevents CHS by inhibiting selectin ligand activity and the capacity of effector T cells to enter antigen-challenged skin without affecting the afferent phase of CHS. PMID:14523038

  5. Synchronous Upper and Lower Gastrointestinal Mucosa-Associated Lymphoid Tissue Lymphomas

    PubMed Central

    McFarlane, Michael; Wong, John Lin Hieng; Paneesha, Shankara; Rudzki, Zbigniew; Arasaradnam, Ramesh; Nwokolo, Chuka

    2016-01-01

    Mucosa-associated lymphoid tissue lymphoma (MALToma) is a subtype of B-cell non-Hodgkin's lymphoma, comprising ∼17% of all gastrointestinal (GI) tract lymphomas. It is associated with chronic inflammation and autoimmunity, for example Helicobacter pylori gastritis and Sjogren's syndrome, respectively. Approximately 50% of GI MALTomas occur in the stomach, with small bowel and colonic lesions being less frequent. Synchronous upper and lower GI MALTomas occur rarely, with few cases reported. We present the case of a 73-year-old patient who presented with change in bowel habit and was found to have synchronous multifocal upper and lower GI MALTomas, which did not respond to H. pylori cure or to rituximab therapy, but did respond to a combination of surgery and chemotherapy with rituximab and bendamustine.

  6. Effects of aging in the expression of NOD-like receptors and inflammasome-related genes in oral mucosa.

    PubMed

    Ebersole, J L; Kirakodu, S; Novak, M J; Exposto, C R; Stromberg, A J; Shen, S; Orraca, L; Gonzalez-Martinez, J; Gonzalez, O A

    2016-02-01

    The molecular changes underlying the higher risk of chronic inflammatory disorders during aging remain incompletely understood. Molecular variations in the innate immune response related to recognition and interaction with microbes at mucosal surfaces could be involved in aging-related inflammation. We developed an ontology analysis of 20 nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) and seven inflammasome-related genes (IRGs) in healthy and inflamed/periodontitis oral mucosal tissues from young, adolescent, adult, and aged non-human primates (Macaca mulatta) using the GeneChip(®) Rhesus Macaque Genome array. Validation of some of the significant changes was done by quantitative reverse transcription-polymerase chain reaction. The expression of NLRB/NAIP, NLRP12, and AIM2 increased with aging in healthy mucosa whereas NLRC2/NOD2 expression decreased. Although higher expression levels of some NLRs were generally observed with periodontitis in adult mucosal tissues (e.g. NLRB/NAIP, NLRP5, and NLRX1), various receptors (e.g. NLRC2/NOD2 and NLRP2) and the inflammasome adaptor protein ASC, exhibited a significant reduction in expression in aged periodontitis tissues. Accordingly, the expression of NLR-activated innate immune genes, such as HBD3 and IFNB1, was impaired in aged but not adult periodontitis tissues. Both adult and aged tissues showed significant increase in interleukin-1β expression. These findings suggest that the expression of a subset of NLRs appears to change with aging in healthy oral mucosa, and that aging-related oral mucosal inflammation could involve an impaired regulation of the inflammatory and antimicrobial response associated with downregulation of specific NLRs and IRGs. PMID:26197995

  7. Spontaneous intramural hematoma of the colon.

    PubMed

    Fernandes, Samuel; Gonçalves, Ana Rita; Araújo Correia, Luís

    2016-08-01

    A 73-year-old man was admitted to our clinic with sudden left quadrant abdominal pain and hematochezia. There was no history of trauma. He denied other symptoms or taking off-the-counter medication. His medical history was relevant for ischemic and aortic-mitral valve disease with prosthetic valves for which he was medicated with aspirin and warfarin. On physical examination the patient presented normal vital signs with tenderness on palpation of the left side of the abdomen. Laboratory tests revealed moderate anemia (10.8 g/dl) and thrombocytopenia (135.000x10^9 U/L) with therapeutic international normalized ratio (2.53). Colonoscopy revealed an extensive area of erythematous and bluish mucosa with an apparent torsion of the proximal descending colon around a volumous hematoma measuring 6.5x3 cm (Figure 1 A-C). Urgent abdominal CT confirmed the presence of a large intramural hematoma of the descending colon (Figure 2 A-B). A conservative approach was adopted with temporary suspension of anticoagulation. Given the high thrombotic risk, abdominal ultrasound was performed after 72 hours showing considerable reduction in the size of the hematoma. Anti-coagulation was then resumed without complications. One month later, colonoscopy was repeated showing complete healing of the mucosa. The increasing use of anti-aggregating and anti-coagulant therapy, especially in elderly patients, explains the increasing incidence of bleeding events seen in this population. However, gastrointestinal hematomas are estimated to occur in only 1 for every 250.000 anti-coagulated patients. Diagnosis is based on characteristic radiologic findings. While most parietal hematomas can be approached conservatively, surgery is indicated in the presence of complications or persistence of the hematoma. PMID:27554386

  8. Obscure bleeding colonic duplication responds to proton pump inhibitor therapy.

    PubMed

    Jacques, Jérémie; Projetti, Fabrice; Legros, Romain; Valgueblasse, Virginie; Sarabi, Matthieu; Carrier, Paul; Fredon, Fabien; Bouvier, Stéphane; Loustaud-Ratti, Véronique; Sautereau, Denis

    2013-09-21

    We report the case of a 17-year-old male admitted to our academic hospital with massive rectal bleeding. Since childhood he had reported recurrent gastrointestinal bleeding and had two exploratory laparotomies 5 and 2 years previously. An emergency abdominal computed tomography scan, gastroscopy and colonoscopy, performed after hemodynamic stabilization, were considered normal. High-dose intravenous proton pump inhibitor (PPI) therapy was initiated and bleeding stopped spontaneously. Two other massive rectal bleeds occurred 8 h after each cessation of PPI which led to a hemostatic laparotomy after negative gastroscopy and small bowel capsule endoscopy. This showed long tubular duplication of the right colon, with fresh blood in the duplicated colon. Obscure lower gastrointestinal bleeding is a difficult medical situation and potentially life-threatening. The presence of ulcerated ectopic gastric mucosa in the colonic duplication explains the partial efficacy of PPI therapy. Obscure gastrointestinal bleeding responding to empiric anti-acid therapy should probably evoke the diagnosis of bleeding ectopic gastric mucosa such as Meckel's diverticulum or gastrointestinal duplication, and gastroenterologists should be aware of this potential medical situation. PMID:24124344

  9. Catecholamine-Directed Epithelial Cell Interactions with Bacteria in the Intestinal Mucosa.

    PubMed

    Brown, David R

    2016-01-01

    The catecholamines epinephrine, norepinephrine and dopamine are present in or have access to mucous membranes in the digestive, respiratory and genitourinary tracts, which represent the first sites of microbial colonization and infection within the body. Epithelial cells at mucosal surfaces establish and maintain symbiotic microbial communities and serve as the initial cellular point of contact for pathogens with the animal host. These cells express receptors that are capable of detecting and responding to microbe-associated molecular patterns and in most host species express G protein-coupled receptors for catecholamines. Although it is increasingly recognized that substances produced and released from nerves and endocrine cells can exert immuno-modulatory actions at mucosal sites, there have been few investigations focused specifically on the catecholaminergic modulation of interactions between the mucosal epithelium and bacteria or other mucosa-associated microorganisms. The potential biomedical importance of this phenomenon cannot be understated. For example, psychological stress or other conditions that activate the sympathetic nervous system to release epinephrine and norepinephrine may act to produce short-term changes in luminal and mucosal microbial communities or alter the course of a bacterial infection. This chapter will briefly review this developing and important research area of mucosa-microbe interactions with a focus on intestinal host defense. PMID:26589214

  10. Colonic health: fermentation and short chain fatty acids.

    PubMed

    Wong, Julia M W; de Souza, Russell; Kendall, Cyril W C; Emam, Azadeh; Jenkins, David J A

    2006-03-01

    Interest has been recently rekindled in short chain fatty acids (SCFAs) with the emergence of prebiotics and probiotics aimed at improving colonic and systemic health. Dietary carbohydrates, specifically resistant starches and dietary fiber, are substrates for fermentation that produce SCFAs, primarily acetate, propionate, and butyrate, as end products. The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source and gut transit time. SCFAs are readily absorbed. Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues. Specific SCFA may reduce the risk of developing gastrointestinal disorders, cancer, and cardiovascular disease. Acetate is the principal SCFA in the colon, and after absorption it has been shown to increase cholesterol synthesis. However, propionate, a gluconeogenerator, has been shown to inhibit cholesterol synthesis. Therefore, substrates that can decrease the acetate: propionate ratio may reduce serum lipids and possibly cardiovascular disease risk. Butyrate has been studied for its role in nourishing the colonic mucosa and in the prevention of cancer of the colon, by promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme histone deacetylase and decreasing the transformation of primary to secondary bile acids as a result of colonic acidification. Therefore, a greater increase in SCFA production and potentially a greater delivery of SCFA, specifically butyrate, to the distal colon may result in a protective effect. Butyrate irrigation (enema) has also been suggested in the treatment of colitis. More human studies are now needed, especially, given the diverse nature of carbohydrate substrates and the SCFA patterns resulting from their fermentation. Short-term and long-term human studies are

  11. In situ characterization of inflammatory responses in the rectal mucosae of patients with shigellosis.

    PubMed Central

    Islam, D; Veress, B; Bardhan, P K; Lindberg, A A; Christensson, B

    1997-01-01

    Shigella species cause bacillary dysentery in humans by invading epithelial cells of the colonic mucosa leading to colonic epithelial cell destruction and inflammation. For further analysis of local gut inflammation, morphological changes and the potential involvement of mediators in regulatory mechanisms of cell activation and cell proliferation were studied immunohistochemically in rectal mucosal biopsies taken from patients during the acute phase of shigellosis and at convalescence. Rectal biopsies from 25 Shigella dysenteriae-1 and 10 Shigella flexneri-infected patients and from 40 controls were studied. The frequencies of proliferative cells (Ki67-positive cells), p53-immunostaining cells, and cells coexpressing Ki67 with CD3 or with p53 were analyzed. Immunostaining for the inducible nitric oxide synthase (iNOS) and the endothelial NOS was assessed. In addition, the frequencies of apoptotic cells and CD68+ cells that engulf apoptotic cells were assessed. By morphological grading, 20% of the patients had advanced inflammation (grade 3) in the acute phase; mild inflammation (grade 1) was seen in 37% of the patients at convalescence as well as in 10% of the controls. The findings in the present study suggest that in the acute phase of shigellosis inflammation is characterized by increased cell turnover in the lamina propria (LP) and the epithelium, increased iNOS expression in the surface epithelium, and apoptosis, which seems to be associated with LP macrophages. The findings also suggest that neither p53 nor iNOS are important factors for the induction of apoptosis in shigellosis. Expression of p53 may be related to early cell activation in crypt epithelium. Moreover, there is an indication of an active, low-level inflammatory process at convalescence. The results thus indicate that Shigella-induced inflammation is associated with a complex series of cellular reactions in the rectal gut mucosa which persist long after clinical symptoms have resolved. PMID

  12. Colonic inflammation and secondary bile acids in alcoholic cirrhosis

    PubMed Central

    Kakiyama, Genta; Hylemon, Phillip B.; Zhou, Huiping; Pandak, William M.; Heuman, Douglas M.; Kang, Dae Joong; Takei, Hajime; Nittono, Hiroshi; Ridlon, Jason M.; Fuchs, Michael; Gurley, Emily C.; Wang, Yun; Liu, Runping; Sanyal, Arun J.; Gillevet, Patrick M.

    2014-01-01

    Alcohol abuse with/without cirrhosis is associated with an impaired gut barrier and inflammation. Gut microbiota can transform primary bile acids (BA) to secondary BAs, which can adversely impact the gut barrier. The purpose of this study was to define the effect of active alcohol intake on fecal BA levels and ileal and colonic inflammation in cirrhosis. Five age-matched groups {two noncirrhotic (control and drinkers) and three cirrhotic [nondrinkers/nonalcoholics (NAlc), abstinent alcoholic for >3 mo (AbsAlc), currently drinking (CurrAlc)]} were included. Fecal and serum BA analysis, serum endotoxin, and stool microbiota using pyrosequencing were performed. A subgroup of controls, NAlc, and CurrAlc underwent ileal and sigmoid colonic biopsies on which mRNA expression of TNF-α, IL-1β, IL-6, and cyclooxygenase-2 (Cox-2) were performed. One hundred three patients (19 healthy, 6 noncirrhotic drinkers, 10 CurrAlc, 38 AbsAlc, and 30 NAlc, age 56 yr, median MELD: 10.5) were included. Five each of healthy, CurrAlc, and NAlc underwent ileal/colonic biopsies. Endotoxin, serum-conjugated DCA and stool total BAs, and secondary-to-primary BA ratios were highest in current drinkers. On biopsies, a significantly higher mRNA expression of TNF-α, IL-1β, IL-6, and Cox-2 in colon but not ileum was seen in CurrAlc compared with NAlc and controls. Active alcohol use in cirrhosis is associated with a significant increase in the secondary BA formation compared with abstinent alcoholic cirrhotics and nonalcoholic cirrhotics. This increase in secondary BAs is associated with a significant increase in expression of inflammatory cytokines in colonic mucosa but not ileal mucosa, which may contribute to alcohol-induced gut barrier injury. PMID:24699327

  13. Colonization and distribution of segmented filamentous bacteria (SFB) in chicken gastrointestinal tract and their relationship with host immunity.

    PubMed

    Liao, Ningbo; Yin, Yeshi; Sun, Guochang; Xiang, Charlie; Liu, Donghong; Yu, Hongwei D; Wang, Xin

    2012-08-01

    Uncultivable segmented filamentous bacteria (SFB) reside in the gastrointestinal (GI) tract of mammals and can boost the host immunity. Immunoglobulin A (IgA) from mother's milk has been previously shown to be a key factor in regulating SFB colonization. Because neonatal chicken cannot acquire IgA from maternal milk, they are a good model to examine the role of IgA in SFB colonization. Here, we used the fluorescent in situ hybridization (FISH) and quantitative PCR (qPCR) to monitor the colonization and distribution of SFB in chickens aged from 2-day-old to 6-week-old. Early SFB colonization, which primarily occurred in the ileal mucosa (< 13 days old), was IgA independent. From the age of 17-42 days, there was an increase in IgA in the gut mucosa, which was correlated with a decrease in SFB. To examine the effect of probiotics and immunosuppression on SFB colonization, we treated the chickens by feeding them Lactobacillus delbrueckii or giving them a subcutaneous injection of cyclophosphamide (CTX). Feeding lactobacilli at birth rendered SFB colonization occurring 4 days earlier, while CTX treatment increases the SFB colonization through reducing the other non-SFB bacteria. Altogether, our data suggest that early colonization of SFB in chicken occurs independently of IgA and the population of SFB in the GI tract of chicken may be manipulated from birth via probiotic or CTX treatment. PMID:22429007

  14. Detection of human papillomavirus infection by molecular tests and its relation to colonic polyps and colorectal cancer

    PubMed Central

    Gazzaz, Faten; Mosli, Mahmoud H.; Jawa, Hani; Sibiany, Abdulrahman

    2016-01-01

    Objectives: To prospectively examine the association between human papilloma virus (HPV) colonization of the colonic mucosa and the development of colorectal polyps (CRPs), and colorectal cancer (CRC) in Saudi Arabia. Methods: A case control study was performed between January 2013 and December 2014. All eligible patients underwent standard diagnostic colonoscopy. Patients with polyps or colorectal cancer were considered cases, while those with any other endoscopic findings were controls. Biopsy samples from polyps and tumors, and/or from normal colonic mucosa were acquired. Human papilloma virus colonization was detected using a hybrid capture technique of samples taken from both normal tissue, and CRPs and CRC. The association between HPV and CRPs/CRC was evaluated. Results: A total of 132 patients were recruited. The mean age was 53 (±15.9) years. Sixty patients had endoscopically detectable CRPs/CRC, and 72 had either inflammation or normal endoscopic evaluations. Only 4 (0.8%) of the 132 samples that were collected and analyzed were positive for the HPV gene. Statistical analysis did not identify any significant association between HPV colonization and the presence of CRPs/CRC. The only significant predictor of detecting CRPs/CRC on colonoscopy was symptomatic presentation (odds ratio=11.072, 95% confidence interval 4.7-26.2, p<0.001). Conclusion: Human papilloma virus colonic colonization is rare in Saudi Arabia. An association between HPV colonization and CRP/CRC development could not be identified in this cohort of patients. PMID:26905346

  15. A Case of Sigmoid Colon Tuberculosis Mimicking Colon Cancer

    PubMed Central

    Yu, Seong-Min; 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 colon, in descending order. Hence, we report a case of intestinal tuberculosis in the sigmoid colon, which is rare and almost indistinguishable from colon cancer. PMID:23185709

  16. Cell volume regulation in goldfish intestinal mucosa.

    PubMed

    Groot, J A

    1981-11-01

    1. Ion and water content of goldfish intestinal mucosa, stripped free from muscular layers were measured under various incubation conditions. 2. Ouabain induces an increase in cation content that is electrically compensated for by chloride. The increase in solute content is accompanied by an increase in water content. 3. When extracellular chloride is partially replaced by sulphate, ouabain does induce cell shrinkage. 4. Anoxia induces a rapid increase in cell volume that is restored by oxygenation of the incubation solution. Ouabain prevents the restoration of volume. 5. It is concluded that the classical ouabain-sensitive Na/K pump participates in the maintenance of cellular volume. We suggest that the constancy in volume after ouabain poisoning as is reported for many tissues might be due to a low chloride conductance of its membranes. 6. Anisotonic media (range: 0.6-1.2 isotonicity), made by variation on mannitol concentration, induce changes in cell water content that deviates from the simplified van't Hoff equation by about 10%. No change in water content after the initial increase was found. 7. We conclude that goldfish enterocytes do not possess a mechanism for rapid volume readjustment. PMID:7322833

  17. Condyloma acuminatum of the buccal mucosa.

    PubMed

    Jaiswal, Rashmi; Pandey, Manoj; Shukla, Mridula; Kumar, Mohan

    2014-06-01

    Condyloma acuminatum is a human papillomavirus (HPV)-induced disease. It is usually transmitted sexually, and it frequently occurs in the anogenital area. A finding of condyloma acuminatum in the oral cavity is rare. Besides HPV, other risk factors for oral condyloma include chewing betel quid and smoking. We report the case of a 52-year-old man who presented with a 2 × 2-cm verrucous white patch on his buccal mucosa. He was habituated to both betel quid and cigarette smoking. A biopsy of the lesion identified it as a verrucous hyperplasia of the squamous epithelium with HPV-related koilocytic changes. The lesion was excised, and further histopathology identified it as condyloma acuminatum. The patient was disease-free 9 months postoperatively. The possibility of condyloma acuminatum should be considered in the differential diagnosis of an oral white lesion. The most common treatments are surgical excision, cryosurgery, electrocautery, and laser excision. There is no known role for antiviral therapy. PMID:24932820

  18. Limited up-regulation of DNA methyltransferase in human colon cancer reflecting increased cell proliferation.

    PubMed Central

    Lee, P J; Washer, L L; Law, D J; Boland, C R; Horon, I L; Feinberg, A P

    1996-01-01

    Epigenetic alterations in the genome of tumor cells have attracted considerable attention since the discovery of widespread alterations in DNA methylation of colorectal cancers over 10 years ago. However, the mechanism of these changes has remained obscure. el-Deiry and coworkers [el-Deiry, W. S., Nelkin, B. D., Celano, P., Yen, R. C., Falco, J. P., Hamilton, S. R. & Baylin, S. B. (1991) Proc. Natl. Acad. Sci. USA 88, 3470-3474], using a quantitative reverse transcription-PCR assay, reported 15-fold increased expression of DNA methyltransferase (MTase) in colon cancer, compared with matched normal colon mucosa, and a 200-fold increase in MTase mRNA levels compared with mucosa of unaffected patients. These authors suggested that increases in MTase mRNA levels play a direct pathogenetic role in colon carcinogenesis. To test this hypothesis, we developed a sensitive quantitative RNase protection assay of MTase, linear over three orders of magnitude. Using this assay on 12 colorectal carcinomas and matched normal mucosal specimens, we observed a 1.8- to 2.5-fold increase in MTase mRNA levels in colon carcinoma compared with levels in normal mucosa from the same patients. There was no significant difference between the normal mucosa of affected and unaffected patients. Furthermore, when the assay was normalized to histone H4 expression, a measure of S-phase-specific expression, the moderate increase in tumor MTase mRNA levels was no longer observed. These data are in contrast to the previously reported results, and they indicate that changes in MTase mRNA levels in colon cancer are nonspecific and compatible with other markers of cell proliferation. Images Fig. 2 PMID:8816806

  19. Biomechanical Signals Inhibit IKK Activity to Attenuate NF-κB Transcription Activity in Inflamed Chondrocytes

    PubMed Central

    Dossumbekova, Anar; Anghelina, Mirela; Madhavan, Shashi; He, Lingli; Quan, Ning; Knobloch, Thomas; Agarwal, Sudha

    2016-01-01

    Objective While the effects of biomechanical signals in the form of joint movement and exercise are known to be beneficial to inflamed joints, limited information is available regarding the intracellular mechanisms of their actions. This study was undertaken to examine the intracellular mechanisms by which biomechanical signals suppress proinflammatory gene induction by the interleukin-1-β (IL-1β)–induced NF-κB signaling cascade in articular chondrocytes. Methods Primary rat articular chondrocytes were exposed to biomechanical signals in the form of cyclic tensile strain, and the effects on the NF-κB signaling cascade were examined by Western blot analysis, real-time polymerase chain reaction, and immunofluorescence. Results Cyclic tensile strain rapidly inhibited the IL-1β–induced nuclear translocation of NF-κB, but not its IL-1β–induced phosphorylation at serine 276 and serine 536, which are necessary for its transactivation and transcriptional efficacy, respectively. Examination of upstream events revealed that cyclic tensile strain also inhibited the cytoplasmic protein degradation of IκBβ and IκBα, as well as repressed their gene transcription. Additionally, cyclic tensile strain induced a rapid nuclear translocation of IκBα to potentially prevent NF-κB binding to DNA. Furthermore, the inhibition of IL-1β–induced degradation of IκB by cyclic tensile strain was mediated by down-regulation of IκB kinase activity. Conclusion These results indicate that the signals generated by cyclic tensile strain act at multiple sites within the NF-κB signaling cascade to inhibit IL-1β–induced proinflammatory gene induction. Taken together, these findings provide insight into how biomechanical signals regulate and reduce inflammation, and underscore their potential in enhancing the ability of chondrocytes to curb inflammation in diseased joints. PMID:17907174

  20. Vascular Deposition Patterns for Nanoparticles in an Inflamed Patient-Specific Arterial Tree

    PubMed Central

    Hossain, Shaolie S.; Hughes, Thomas J.R.; Decuzzi, Paolo

    2014-01-01

    Inflammation, a precursor to many diseases including cancer and atherosclerosis, induces differential surface expression of specific vascular molecules. Blood-borne nanoparticles (NPs), loaded with therapeutic and imaging agents, can recognize and use these molecules as vascular docking sites. Here, a computational model is developed within the Isogeometric Analysis framework to understand and predict the vascular deposition of NPs within an inflamed arterial tree. The NPs have a diameter ranging from 0.1 to 2.0 μm and are decorated with antibodies directed toward three endothelial adhesion molecules, namely intravascular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, whose surface density depends on the local wall shear stress. Results indicate VCAM-1 targeted NPs adhere more, with ICAM-1 directed NPs adhering least efficiently, resulting in approximately an order-of-magnitude lower average particle surface density. ICAM-1 and E-selectin directed 0.5 μm NPs are distributed more uniformly (heterogeneity index ≈ 0.9 and 1.0, respectively) over the bifurcating vascular branches compared to their VCAM-1 counterparts (heterogeneity index ≈ 1.4). When the NPs are coated with antibodies for VCAM-1 and E-selectin in equal proportions, a more uniform vascular distribution is achieved compared with VCAM-1-only targeted particles, thus demonstrating the advantage of NP multivalency in vascular targeting. Furthermore, the larger NPs (2 μm) adhere more (≈ 200%) in the lower branches compared to the upper branch. This computational framework provides insights into how size, ligand type, density, and multivalency can be manipulated to enhance NP vascular adhesion in an individual patient. PMID:23942910

  1. MR Imaging of Myeloperoxidase Activity in a Model of the Inflamed Aneurysm Wall

    PubMed Central

    Gounis, M.J.; van der Bom, I.M.J.; Wakhloo, A.K.; Zheng, S.; Chueh, J.-Y.; Kühn, A.L.; Bogdanov, A.A.

    2014-01-01

    Background and Purpose Although myeloperoxidase (MPO) activity in vivo can be visualized using non-invasive imaging, successful clinical translation requires further optimization of the imaging approach. We report a motion-sensitized-driven-equilibrium (MSDE) for the detection of an MPO activity-specific gadolinium (Gd)-containing imaging agent (IA) in experimental aneurysm models that compensates for irregular blood flow enabling vascular wall imaging in the aneurysm. Materials and Methods We deployed a phantom model to optimize a MSDE MR sequence that suppresses complex flow patterns within the aneurysm for detection of an MPO-specific Gd-chelate. The phantom was built from rotational angiography of a rabbit elastase aneurysm model and connected to a cardiac pulse duplicator mimicking rabbit-specific flow conditions. Thereafter, we further refined the MSDE sequence and applied it in vivo to rabbit aneurysm models with and without inflammation in the aneurysmal wall. Under each condition, the aneurysms were imaged before and after intravenous administration of the IA. The signal-to-noise ratio (SNR) of each MR slice through the aneurysm was calculated. Results The MSDE sequence was optimized to reduce flow signal enabling detection of the MPO-IA in the phantom. The optimized imaging protocol in the rabbit model of saccular aneurysms revealed a significant increase in the change of SNR pre- to postcontrast MR signal intensities in the inflamed aneurysms as compared to naïve aneurysms and the adjacent carotid artery (p<0.0001). Conclusion A diagnostic MR protocol was optimized for molecular imaging of an MPO-specific molecular imaging agent in an animal model of brain aneurysms. PMID:25273534

  2. Model-based recovery of histological parameters from multispectral images of the colon

    NASA Astrophysics Data System (ADS)

    Hidovic-Rowe, Dzena; Claridge, Ela

    2005-04-01

    Colon cancer alters the macroarchitecture of the colon tissue. Common changes include angiogenesis and the distortion of the tissue collagen matrix. Such changes affect the colon colouration. This paper presents the principles of a novel optical imaging method capable of extracting parameters depicting histological quantities of the colon. The method is based on a computational, physics-based model of light interaction with tissue. The colon structure is represented by three layers: mucosa, submucosa and muscle layer. Optical properties of the layers are defined by molar concentration and absorption coefficients of haemoglobins; the size and density of collagen fibres; the thickness of the layer and the refractive indexes of collagen and the medium. Using the entire histologically plausible ranges for these parameters, a cross-reference is created computationally between the histological quantities and the associated spectra. The output of the model was compared to experimental data acquired in vivo from 57 histologically confirmed normal and abnormal tissue samples and histological parameters were extracted. The model produced spectra which match well the measured data, with the corresponding spectral parameters being well within histologically plausible ranges. Parameters extracted for the abnormal spectra showed the increase in blood volume fraction and changes in collagen pattern characteristic of the colon cancer. The spectra extracted from multi-spectral images of ex-vivo colon including adenocarcinoma show the characteristic features associated with normal and abnormal colon tissue. These findings suggest that it should be possible to compute histological quantities for the colon from the multi-spectral images.

  3. TPX2 is a novel prognostic marker for the growth and metastasis of colon cancer

    PubMed Central

    2013-01-01

    Background We have previously demonstrated an aberrant overexpression of the microtubule-associated protein TPX2 in colon cancer using a genome-wide gene expression profiling analysis. Here, we aim to investigate its expression pattern, clinical significance, and biological function in colon cancer. Methods TPX2 expression was analyzed in human colon cancer cell lines and tumor samples. The effect of TPX2 on cell proliferation, tumorigenesis, and metastasis was examined in vitro and in vivo. Results TPX2 was overexpressed in 129 of the 203 (60.8%) colon cancer metastatic lesions, with the expression being significantly higher than that in primary cancerous tissue and normal colon mucosa. Overexpression of TPX2 was significantly associated with clinical staging, vessel invasion, and metastasis. In survival analyses, patients with TPX2 overexpression had worse overall survival and metastasis free survival, suggesting that deregulation of TPX2 may contribute to the metastasis of colon cancer. Consistent with this, suppression of TPX2 expression inhibited proliferation and tumorigenicity of colon cancer cells both in vitro and in vivo. Strikingly, we found that TPX2 knockdown significantly attenuated the migration and invasion ability of colon cancer cells, which was further shown to be mechanistically associated with AKT-mediated MMP2 activity. Conclusions These findings suggest that TPX2 plays an important role in promoting tumorigenesis and metastasis of human colon cancer, and may represent a novel prognostic biomarker and therapeutic target for the disease. PMID:24341487

  4. Automatic colonic lesion detection and tracking in endoscopic videos

    NASA Astrophysics Data System (ADS)

    Li, Wenjing; Gustafsson, Ulf; A-Rahim, Yoursif

    2011-03-01

    The biology of colorectal cancer offers an opportunity for both early detection and prevention. Compared with other imaging modalities, optical colonoscopy is the procedure of choice for simultaneous detection and removal of colonic polyps. Computer assisted screening makes it possible to assist physicians and potentially improve the accuracy of the diagnostic decision during the exam. This paper presents an unsupervised method to detect and track colonic lesions in endoscopic videos. The aim of the lesion screening and tracking is to facilitate detection of polyps and abnormal mucosa in real time as the physician is performing the procedure. For colonic lesion detection, the conventional marker controlled watershed based segmentation is used to segment the colonic lesions, followed by an adaptive ellipse fitting strategy to further validate the shape. For colonic lesion tracking, a mean shift tracker with background modeling is used to track the target region from the detection phase. The approach has been tested on colonoscopy videos acquired during regular colonoscopic procedures and demonstrated promising results.

  5. Inhibition of azoxymethane-induced colon cancer by orange juice.

    PubMed

    Miyagi, Y; Om, A S; Chee, K M; Bennink, M R

    2000-01-01

    Previous research has shown that hesperidin, a flavanone glycoside in orange juice, inhibits colon carcinogenesis and that feeding double-strength orange juice delays the onset of chemically induced mammary cancer in rats. This study determined whether feeding single-strength, pasteurized orange juice would inhibit azoxymethane (AOM)-induced colon cancer in male Fischer 344 rats. Colon cancer was initiated by injecting AOM (15 mg/kg body wt) at 22 and 29 days of age. One week after the second AOM injection, orange juice replaced drinking water for the experimental group (n = 30). The rats were killed 28 weeks later, and tumors were removed for histological analysis. Feeding orange juice reduced tumor incidence by 22% (p < 0.05). Tumor reduction was associated with a decreased labeling index and proliferation zone in the colonic mucosa. Hesperidin, other flavonoids, limonin 17-beta-D-glucopyranoside, and other limonoid glucosides are potential chemopreventive agents in orange juice that could account for the decreased colon tumorigenesis associated with feeding orange juice. PMID:10890034

  6. Folate transport gene inactivation in mice increases sensitivity to colon carcinogenesis.

    PubMed

    Ma, David W L; Finnell, Richard H; Davidson, Laurie A; Callaway, Evelyn S; Spiegelstein, Ofer; Piedrahita, Jorge A; Salbaum, J Michael; Kappen, Claudia; Weeks, Brad R; James, Jill; Bozinov, Daniel; Lupton, Joanne R; Chapkin, Robert S

    2005-02-01

    Low dietary folate intake is associated with an increased risk for colon cancer; however, relevant genetic animal models are lacking. We therefore investigated the effect of targeted ablation of two folate transport genes, folate binding protein 1 (Folbp1) and reduced folate carrier 1 (RFC1), on folate homeostasis to elucidate the molecular mechanisms of folate action on colonocyte cell proliferation, gene expression, and colon carcinogenesis. Targeted deletion of Folbp1 (Folbp1(+/-) and Folbp1(-/-)) significantly reduced (P < 0.05) colonic Folbp1 mRNA, colonic mucosa, and plasma folate concentration. In contrast, subtle changes in folate homeostasis resulted from targeted deletion of RFC1 (RFC1(+/-)). These animals had reduced (P < 0.05) colonic RFC1 mRNA and exhibited a 2-fold reduction in the plasma S-adenosylmethionine/S-adenosylhomocysteine. Folbp1(+/-) and Folbp1(-/-) mice had larger crypts expressed as greater (P < 0.05) numbers of cells per crypt column relative to Folbp1(+/+) mice. Colonic cell proliferation was increased in RFC1(+/-) mice relative to RFC1(+/+) mice. Microarray analysis of colonic mucosa showed distinct changes in gene expression specific to Folbp1 or RFC1 ablation. The effect of folate transporter gene ablation on colon carcinogenesis was evaluated 8 and 38 weeks post-azoxymethane injection in wild-type and heterozygous mice. Relative to RFC1(+/+) mice, RFC1(+/-) mice developed increased (P < 0.05) numbers of aberrant crypt foci at 8 weeks. At 38 weeks, RFC1(+/-) mice developed local inflammatory lesions with or without epithelial dysplasia as well as adenocarcinomas, which were larger relative to RFC1(+/+) mice. In contrast, Folbp1(+/-) mice developed 4-fold (P < 0.05) more lesions relative to Folbp1(+/+) mice. In conclusion, Folbp1 and RFC1 genetically modified mice exhibit distinct changes in colonocyte phenotype and therefore have utility as models to examine the role of folate homeostasis in colon cancer development. PMID:15705887

  7. Nonlinear optical imaging characteristics of colonic adenocarcinoma using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Liu, Nenrong; Chen, Rong; Li, Hongsheng; Chen, Jianxin

    2012-12-01

    Multiphoton microscopy (MPM), a noninvasive optical method with high resolution and high sensitivity, can obtain detailed microstructures of biotissues at submolecular level. In this study, MPM is used to image microstructure varieties of human colonic mucosa and submucosa with adenocarcinoma. Some parameters, such as gland configuration, SHG/TPEF intensity ratio, and collagen orientation and so on, should serve the indicators of early colorectal cancer. The exploratory results show that it's potential for the development of multiphoton mini-endoscopy in real-time early diagnosis of colorectal cancer.

  8. Role of the A2B receptor–adenosine deaminase complex in colonic dysmotility associated with bowel inflammation in rats

    PubMed Central

    Antonioli, L; Fornai, M; Awwad, O; Giustarini, G; Pellegrini, C; Tuccori, M; Caputi, V; Qesari, M; Castagliuolo, I; Brun, P; Giron, M C; Scarpignato, C; Blandizzi, C; Colucci, R

    2014-01-01

    BACKGROUND AND PURPOSE Adenosine A2B receptors regulate several physiological enteric functions. However, their role in the pathophysiology of intestinal dysmotility associated with inflammation has not been elucidated. Hence, we investigated the expression of A2B receptors in rat colon and their role in the control of cholinergic motility in the presence of bowel inflammation. EXPERIMENTAL APPROACH Colitis was induced by 2,4-dinitrobenzenesulfonic acid (DNBS). Colonic A2B receptor expression and localization were examined by RT-PCR and immunofluorescence. The interaction between A2B receptors and adenosine deaminase was assayed by immunoprecipitation. The role of A2B receptors in the control of colonic motility was examined in functional experiments on longitudinal muscle preparations (LMPs). KEY RESULTS A2B receptor mRNA was present in colon from both normal and DNBS-treated rats but levels were increased in the latter. A2B receptors were predominantly located in the neuromuscular layer, but, in the presence of colitis, were increased mainly in longitudinal muscle. Functionally, the A2B receptor antagonist MRS 1754 enhanced both electrically-evoked and carbachol-induced cholinergic contractions in normal LMPs, but was less effective in inflamed tissues. The A2B receptor agonist NECA decreased colonic cholinergic motility, with increased efficacy in inflamed LMP. Immunoprecipitation and functional tests revealed a link between A2B receptors and adenosine deaminase, which colocalize in the neuromuscular compartment. CONCLUSIONS AND IMPLICATIONS Under normal conditions, endogenous adenosine modulates colonic motility via A2B receptors located in the neuromuscular compartment. In the presence of colitis, this inhibitory control is impaired due to a link between A2B receptors and adenosine deaminase, which catabolizes adenosine, thus preventing A2B receptor activation. PMID:24286264

  9. Inactivation of corticosteroids in intestinal mucosa by 11 beta-hydroxysteroid: NADP oxidoreductase (EC 1. 1. 1. 146)

    SciTech Connect

    Burton, A.F.; Anderson, F.H.

    1983-10-01

    Activity of the enzyme 11 beta-hydroxysteroid:NADP oxidoreductase (EC 1.1.1.146) in human intestinal mucosa was determined by incubating scraped mucosa with /sup 3/H-cortisone and /sup 14/C-cortisol; these steroids were then extracted, separated chromatographically, and the radioactivity assayed to determine simultaneously both reductase and dehydrogenase activities. This was the only significant metabolic alteration which the substrate underwent. Only two cases had slight (5 and 13%) reductase activity. In 35 patients, 16 male and 19 female, including seven cases of Crohn's disease, three ulcerative colitis, five diverticulitis, two undergoing surgery for repair of injuries and 18 for carcinoma of colon or rectum, cortisol was converted to cortisone in 15 min with a wide range of values distributed uniformly up to 85% dehydrogenation, with a mean of 42%. When tissue homogenates were fortified with coenzymes, excess NADPH lowered dehydrogenase activity 81%; excess NADP increased dehydrogenase activity 2-fold in three cases. It is possible that a value is characteristic of an individual but perhaps more likely enzyme activity varies with metabolic events involving changes in the coenzyme levels in mucosa, and a random sampling might be expected to yield such a distribution of values. In any event, where activity is high most of the cortisol is inactivated within minutes. It is suggested that synthetic corticoids which escape such metabolic alteration might, except during pregnancy, prove superior in the treatment of conditions such as inflammatory bowel disease.

  10. Roseomonas mucosa Isolated from Bloodstream of Pediatric Patient ▿

    PubMed Central

    Bard, J. Dien; Deville, J. G.; Summanen, P. H.; Lewinski, M. A.

    2010-01-01

    We report a case of catheter-related bacteremia associated with Roseomonas mucosa isolated from an immunocompromised pediatric patient with a history of multiple episodes of urinary tract infection and bacteremia. PMID:20534804

  11. [Premalignant lesions and conditions of the oral mucosa].

    PubMed

    Bruaset, I

    1989-04-01

    An overview is presented of the premalignant lesions and conditions of the oral mucosa. The dentist can play an important role in the detection of these lesions, thereby reducing the chance of premalignant transformation. PMID:2622509

  12. Effects of garlic preparations on the gastrointestinal mucosa.

    PubMed

    Hoshino, T; Kashimoto, N; Kasuga, S

    2001-03-01

    The effects of garlic preparations, including dehydrated raw garlic powder (RGP), dehydrated boiled garlic powder (BGP) and aged garlic extract (AGE), on the gastric mucosa were determined using a newly established endoscopic air-powder delivery system, which can deliver solid materials directly into the stomach. Among the three preparations, RGP caused severe damage, including erosion. BGP also caused reddening of the mucosa, whereas AGE did not cause any undesirable effects. The safety of enteric-coated garlic products was also determined. Direct administration of pulverized enteric-coated products on the gastric mucosa caused reddening of the mucosa. When an enteric-coated tablet was administered orally, it caused loss of epithelial cells at the top of crypts in the ileum. These results suggest that caution be used with regard to safety and effectiveness when choosing a garlic preparation because some preparations may have undesirable effects, including gastrointestinal problems. PMID:11238827

  13. Evaluation of the mRNA and Protein Expressions of Nutritional Biomarkers in the Gastrointestinal Mucosa of Patients with Small Intestinal Disorders.

    PubMed

    Nakamura, Masanao; Hirooka, Yoshiki; Watanabe, Osamu; Yamamura, Takeshi; Funasaka, Kohei; Ohno, Eizaburo; Miyahara, Ryoji; Kawashima, Hiroki; Shimoyama, Yoshie; Goto, Hidemi

    2016-01-01

    Objective The objectives of this study were to investigate the mRNA and protein expression of biomarkers related to absorption in the small intestinal mucosa of humans and determine the relationships between small intestinal diseases and nutrition. Methods The study subjects consisted of patients scheduled to undergo double-balloon endoscopy (DBE) or total colonoscopy for suspected gastrointestinal disorder in a clinical practice. Biopsies were taken from apparently normal mucosa in the visible areas of 6 parts of the intestines from the duodenum to the colon. The mRNA expression of specific biomarkers (SGLT1, SGLT5, GIP, GLP, LAT1, LAT2, and NPC1L1) in the mucosa was compared among three patient groups: Inflammation, Tumor, and Control. Results Sixty-six patients participated in this study. Both routes of DBE were performed in 20 patients, in whom biopsy samples were obtained from the mucosa for all sections. There were no remarkable differences in the mRNA expression levels among the 3 groups. However, SGLT1, GIP, GLP, and NPC1L1 exhibited specific distribution patterns. The expression levels of GIP and NPC1L1 were highest in the upper jejunum, but were extremely low in the terminal ileum and colon. A comparison of the mRNA expression profile in each intestinal section revealed that the SGLT1 mRNA expression in the Tumor group and the GIP mRNA expression in the Inflammation group were significantly higher than the corresponding levels in the Control group in the upper jejunum. Conclusion The gastrointestinal mucosa of patients with small bowel diseases can maintain proper nutrient absorption, except in the upper jejunum. PMID:27522989

  14. Modulation of cytokine release from colonic explants by bacterial antigens in inflammatory bowel disease.

    PubMed

    Dionne, S; Laberge, S; Deslandres, C; Seidman, E G

    2003-07-01

    The intestinal flora play an important role in experimental colitis and inflammatory bowel disease (IBD). Using colonic explant cultures from 132 IBD and control subjects, we examined tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 and interleukin-1 receptor antagonist (IL-1RA) production in vitro in response to bacterial activators. Unstimulated TNF-alpha release was increased significantly in rectal biopsies from involved IBD tissue, correlating with inflammation severity. Whereas lipopolysaccharide (LPS) only moderately stimulated TNF-alpha production from inflamed tissue, pokeweed mitogen (PWM) induced its release in all groups, with a stronger response in involved IBD tissue. Superantigen staphylococcal enterotoxin A (SEA) had a similar, but weaker effect. SEB was observed to be the strongest inducer of TNF-alpha for all groups, again with a more marked response in inflamed tissue. Stimulated release of IL-1 was considerably less than for TNF-alpha. The superantigens' superior potency over LPS was not as marked for IL-1 as it was for TNF-alpha. In addition to IL-1, IL-1RA release was also triggered by the bacterial products. The net effect of activation on the IL-1RA/IL-1 ratio was relatively modest. Release of the proinflammatory cytokines TNF-alpha and IL-1, as well as that of the anti-inflammatory cytokine IL-1RA was increased by incubation of colonic tissue with bacterial factors. TNF-alpha production and release was increased significantly in involved colonic explants from IBD. SEB was even capable of inducing TNF-alpha release from uninvolved colonic tissue. PMID:12823284

  15. Scap is required for sterol synthesis and crypt growth in intestinal mucosa[S

    PubMed Central

    McFarlane, Matthew R.; Cantoria, Mary Jo; Linden, Albert G.; January, Brandon A.; Liang, Guosheng; Engelking, Luke J.

    2015-01-01

    SREBP cleavage-activating protein (Scap) is an endoplasmic reticulum membrane protein required for cleavage and activation of sterol regulatory element-binding proteins (SREBPs), which activate the transcription of genes in sterol and fatty acid biosynthesis. Liver-specific loss of Scap is well tolerated; hepatic synthesis of sterols and fatty acids is reduced, but mice are otherwise healthy. To determine whether Scap loss is tolerated in the intestine, we generated a mouse model (Vil-Scap−) in which tamoxifen-inducible Cre-ERT2, a fusion protein of Cre recombinase with a mutated ligand binding domain of the human estrogen receptor, ablates Scap in intestinal mucosa. After 4 days of tamoxifen, Vil-Scap− mice succumb with a severe enteropathy and near-complete collapse of intestinal mucosa. Organoids grown ex vivo from intestinal crypts of Vil-Scap− mice are readily killed when Scap is deleted by 4-hydroxytamoxifen. Death is prevented when culture medium is supplemented with cholesterol and oleate. These data show that, unlike the liver, the intestine requires Scap to sustain tissue integrity by maintaining the high levels of lipid synthesis necessary for proliferation of intestinal crypts. PMID:25896350

  16. Relative Transmissibility of an R5 Clade C Simian-Human Immunodeficiency Virus Across Different Mucosae in Macaques Parallels the Relative Risks of Sexual HIV-1 Transmission Via Different Routes

    PubMed Central

    Chenine, Agnès L.; Siddappa, Nagadenahalli B.; Kramer, Victor G.; Sciaranghella, Gaia; Rasmussen, Robert A.; Lee, Sandra J.; Santosuosso, Michael; Poznansky, Mark C.; Velu, Vijayakumar; Amara, Rama R.; Souder, Chris; Anderson, Daniel C.; Villinger, François; Else, James G.; Novembre, Francis J.; Strobert, Elizabeth; O’Neil, Shawn P.; Secor, W. Evan; Ruprecht, Ruth M.

    2010-01-01

    Background Worldwide, ~90% of all HIV transmissions occur mucosally; almost all involve R5 strains. Risks of sexual HIV acquisition are highest for rectal, followed by vaginal and then oral exposures. Methods Mucosal lacerations may affect the rank-order of susceptibility to HIV but cannot be assessed in humans. We measured relative virus transmissibility across intact mucosae in macaques using a single stock of SHIV-1157ipd3N4, a simian-human immunodeficiency virus encoding a primary R5 HIV clade C env (SHIV-C). Results The penetrability of rhesus macaque mucosae differed significantly, with rectal challenge requiring the least virus, followed by the vaginal and then oral routes. These findings imply that intrinsic mucosal properties are responsible for the differential mucosal permeability. The latter paralleled the rank-order reported for humans, with relative risk estimates within the range of epidemiologic human studies. To test whether inflammation facilitates virus transmission – as predicted from human studies – we established a macaque model of localized buccal inflammation. Systemic infection occurred across inflamed, but not normal buccal mucosa. Conclusion Our primate data recapitulate virus transmission risks observed in humans, thus establishing R5 SHIV-1157ipd3N4 in macaques as a robust model system to study cofactors involved in human mucosal HIV transmission and its prevention. PMID:20214475

  17. Morphoclinical aspects of the human paraprostethic gingival mucosa.

    PubMed

    Scrieciu, Monica; Niculescu, Mihaela; Mercuţ, Veronica; Andrei, Victoria; Pancă, Oana Adina

    2005-01-01

    The multiple and various changes that the human gingival mucosa undergoes when coming into contact with a denture, require a histopathological study correlated with that of clinical manifestations. The highlighting of the histological lesions of the prosthetic field's mucosa is extremely important in the study concerning the tolerance of the oral cavity tissues towards the materials of dentures, because it has been observed that different materials can cause the same type of clinical changes. The clinical research has been carried out having as a basis a group of patients, carriers of fixed dentures made of different materials, the study method consisting in their clinical evaluation. The investigation of microscopic preparations, obtained through drawing mucosa from those patients under study, has been made by using both usual colorations for an overall examination of the tissue architecture, as well as special colorations for pointing out certain structures. The results of the investigation have made clear the fact that the clinical changes of the prosthetic field's mucosa can be adaptable to the denture or can react pathologically to the various possibilities of denture aggression. The histopathological picture of the paraprosthetic mucosa lesions is polymorphous due to the morphofunctional complexity as well as to the reacting capacity of the oral mucosa when interfering with a fixed denture. PMID:16688373

  18. Cloning and characterization of a new intestinal inflammation-associated colonic epithelial Ste20-related protein kinase isoform.

    PubMed

    Yan, Y; Nguyen, H; Dalmasso, G; Sitaraman, S V; Merlin, D

    2007-02-01

    Intestinal epithelial cells respond to inflammatory extracellular stimuli by activating mitogen activated protein kinase (MAPK) signaling, which mediates numerous pathophysiological effects, including intestinal inflammation. Here, we show that a novel isoform of SPS1-related proline alanine-rich kinase (SPAK/STE20) is involved in this inflammatory signaling cascade. We cloned and characterized a SPAK isoform from inflamed colon tissue, and found that this SPAK isoform lacked the characteristic PAPA box and alphaF loop found in SPAK. Based on genomic sequence analysis the lack of PAPA box and alphaF loop in colonic SPAK isoform was the result of specific splicing that affect exon 1 and exon 7 of the SPAK gene. The SPAK isoform was found in inflamed and non-inflamed colon tissues as well as Caco2-BBE cells, but not in other tissues, such as liver, spleen, brain, prostate and kidney. In vitro analyses demonstrated that the SPAK isoform possessed serine/threonine kinase activity, which could be abolished by a substitution of isoleucine for the lysine at position 34 in the ATP-binding site of the catalytic domain. Treatment of Caco2-BBE cells with the pro-inflammatory cytokine, interferon gamma, induced expression of the SPAK isoform. Over-expression of the SPAK isoform in Caco2-BBE cells led to nuclear translocation of an N-terminal fragment of the SPAK isoform, as well as activation of p38 MAP kinase signaling cascades and increased intestinal barrier permeability. These findings collectively suggest that pro-inflammatory cytokine signaling may induce expression of this novel SPAK isoform in intestinal epithelia, triggering the signaling cascades that govern intestinal inflammation. PMID:17321610

  19. Uncomplicated Diverticular Disease: Innate and Adaptive Immunity in Human Gut Mucosa before and after Rifaximin

    PubMed Central

    Cesaro, Paola; Petruzziello, Lucio; Casciano, Fabio; Costamagna, Guido; Pandolfi, Franco

    2014-01-01

    Background/Aim. Uncomplicated diverticular disease (UDD) is a frequent condition in adults. The pathogenesis of symptoms remains unknown. Bacteria are able to interact with Toll-like receptors (TLRs) and to induce inflammation through both innate immunity and T-cell recruitment. We investigated the pattern of TLRs 2 and 4 and the intestinal homing in patients with UDD before and after a course of Rifaximin. Methods. Forty consecutive patients with UDD and 20 healthy asymptomatic subjects were enrolled. Among UDD patients, 20 were assigned to a 2-month course of treatment with Rifaximin 1.2 g/day for 15 days/month and 20 received placebo. Blood sample and colonic biopsies were obtained from patients and controls. The samples were collected and analyzed at baseline and at the end of treatment. Flow cytometry was performed using monoclonal antibodies (CD3, CD4, CD8, CD103, TCR-gamma/delta, CD14, TLR2, and TLR4). Results. In UDD, TLR2 and TLR4 expression on immune cell subpopulations from blood and mucosa of the affected colon are altered as compared with controls. Rifaximin treatment induced significant modifications of altered conditions. Conclusions. Our data show the role of TLRs in the development of inflammation in UDD. TLRs distribution is altered in UDD and these alterations are reversed after antibiotic treatment. This trial is registered with ClinicalTrials.gov: NCT02068482. PMID:25133198

  20. Impact of the coxsackievirus and adenovirus receptor on the adenoma–carcinoma sequence of colon cancer

    PubMed Central

    Stecker, K; Vieth, M; Koschel, A; Wiedenmann, B; Röcken, C; Anders, M

    2011-01-01

    Background: Coxsackie and adenovirus receptor (CAR) has been suggested to function as a tumour suppressor. Its impact on the adenoma–carcinoma sequence of the colon, however, is unclear. Methods: Coxsackie and adenovirus receptor was analysed in non-cancerous and neoplastic colon samples using immunohistochemistry and quantitative RT–PCR. The function of CAR in colon cancer cell lines was determined following application of CAR siRNA or ectopic expression of a human full-length CAR cDNA. Results: Compared with healthy mucosa, increased CAR-mRNA expression was found in adenomas, whereas primary cancers and metastases displayed a marked decline. At the plasma membrane, CAR was present in normal mucosa samples (93%), adenomas, and metastases (100% ea.), whereas in colon cancers, it was found less frequently (49%, P<0.0001). Cytoplasmic CAR immunopositivity increased from normal mucosa (22%), to adenomas (73%, P=0.0006), primary cancers (83%, P<0.0001), and metastases (67%, P=0.0019). In cancer cell lines, CAR inhibition resulted in increased proliferation, whereas enforced ectopic CAR expression led to opposite results. Blocking the extracellular portion of CAR increased cell invasion in vitro. In mice, xenotransplants of colon cancer cells with enforced CAR expression formed significantly smaller tumours, whereas CAR inhibition increased the formation of liver metastases. Conclusion: We conclude that CAR facilitates complex effects during colon carcinogenesis, potentially mediated by its stage-dependent subcellular distribution; high CAR expression potentially prevents apoptosis in adenomas, loss of CAR at the plasma membrane promotes growth, and dissemination of primary cancers, and high membranous CAR presence may support the establishment of distant metastases. PMID:21468049

  1. Surgical removal of inflamed epididymal white adipose tissue attenuates the development of non-alcoholic steatohepatitis in obesity

    PubMed Central

    Mulder, P; Morrison, M C; Wielinga, P Y; van Duyvenvoorde, W; Kooistra, T; Kleemann, R

    2016-01-01

    Background: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with abdominal obesity. Growing evidence suggests that inflammation in specific depots of white adipose tissue (WAT) has a key role in NAFLD progression, but experimental evidence for a causal role of WAT is lacking. Methods: A time-course study in C57BL/6J mice was performed to establish which WAT depot is most susceptible to develop inflammation during high-fat diet (HFD)-induced obesity. Crown-like structures (CLS) were quantified in epididymal (eWAT), mesenteric (mWAT) and inguinal/subcutaneous (iWAT) WAT. The contribution of inflamed WAT to NAFLD progression was investigated by surgical removal of a selected WAT depot and compared with sham surgery. Plasma markers were analyzed by enzyme-linked immunosorbent assay (cytokines/adipokines) and lipidomics (lipids). Results: In eWAT, CLS were formed already after 12 weeks of HFD, which coincided with maximal adipocyte size and fat depot mass, and preceded establishment of non-alcoholic steatohepatitis (NASH). By contrast, the number of CLS were low in mWAT and iWAT. Removal of inflamed eWAT after 12 weeks (eWATx group), followed by another 12 weeks of HFD feeding, resulted in significantly reduced NASH in eWATx. Inflammatory cell aggregates (−40% P<0.05) and inflammatory genes (e.g., TNFα, −37% P<0.05) were attenuated in livers of eWATx mice, whereas steatosis was not affected. Concomitantly, plasma concentrations of circulating proinflammatory mediators, viz. leptin and specific saturated and monounsaturated fatty acids, were also reduced in the eWATx group. Conclusions: Intervention in NAFLD progression by removal of inflamed eWAT attenuates the development of NASH and reduces plasma levels of specific inflammatory mediators (cytokines and lipids). These data support the hypothesis that eWAT is causally involved in the pathogenesis of NASH. PMID:26499443

  2. Analgesic effects evoked by a CCR2 antagonist or an anti-CCL2 antibody in inflamed mice.

    PubMed

    Llorián-Salvador, María; Pevida, Marta; González-Rodríguez, Sara; Lastra, Ana; Fernández-García, María-Teresa; Hidalgo, Agustín; Baamonde, Ana; Menéndez, Luis

    2016-06-01

    Chemokine CCL2, also known as monocyte chemoattractant protein-1 (MCP-1), is a molecule that in addition to its well-established role in chemotaxis can also act as nociceptor sensitizer. The upregulation of this chemokine in inflamed tissues could suggest its involvement in inflammatory hypernociception. Thus, we have measured CCL2 levels in mice with acute or chronic inflammation due to the intraplantar (i.pl.) injection of carrageenan or complete Freund's adjuvant (CFA), respectively, and we have studied whether inflammatory hyperalgesia or allodynia could be attenuated by blocking CCR2 receptors or neutralizing CCL2 with an anti-CCL2 antibody. A remarkable increase in CCL2 concentration was detected by ELISA in paw homogenates coming from carrageenan- or CFA-inflamed mice, being its expression mainly localized in macrophages, as shown by immunohistochemical assays. The s.c. (0.3-3 mg/kg) or i.pl. (0.3-3 μg) administration of the CCR2 antagonist, RS 504393, dose dependently inhibited thermal hyperalgesia measured in acutely or chronically inflamed mice, whereas s.c. administration of this drug did not reduce inflammatory mechanical allodynia. Furthermore, the inhibition of inflammatory hyperalgesia after the administration of an anti-CCL2 antibody (0.1-1 μg; i.pl.) suggests that CCL2 could be the endogenous chemokine responsible for CCR2-mediated hyperalgesic effects. Besides, the acute administration of the highest antihyperalgesic dose of RS 504393 assayed did not reduce paw tumefaction or modify the presence of inflammatory cells. These results indicate that the blockade of the CCL2/CCR2 system can counteract inflammatory hyperalgesia, being this antinociceptive effect unrelated to a decrease in the inflammatory reaction. PMID:26820818

  3. Right colon carcinoma infiltrating the alimentary limb in a patient with biliopancreatic diversion.

    PubMed

    López-Tomassetti Fernández, Eudaldo M; Hernández Hernández, Juan Ramón; Jorge, Valentine Nuñez

    2014-01-01

    Biliopancreatic diversion (BPD) has excellent results, with the average patient losing 60% to 80% of the excess weight in the first 2 years. However, the BPD works by malabsorption and malabsorptive problems may be experienced with the operation. Therefore, monitoring is necessary for life. In the recent literature there is some debate over the possibility that this technique can increase the risk of colon cancer secondary to the action of the unabsorbed food and bile acid on colonic mucosa. We report the case of a 42-year-old patient with a previous bariatric surgery (BPD with 50 cm common channel; 300 cm alimentary limb) who developed a very aggressive right colon cancer 6 years after the operation. We also review our series of 330 patients operated on during a 14-year period to try to answer if there is any relationship between BPD and colon cancer. PMID:25058764

  4. Inflammatory "Cap" Polyposis: A Case Report of a Rare Nonneoplastic Colonic Polyposis.

    PubMed

    De Petris, Giovanni; Dhungel, Bal M; Chen, Longwen; Pasha, Shabana F

    2014-06-01

    Inflammatory cap polyposis (ICP) is a rare nonneoplastic polyposis of the colon of unknown etiology that can be confused with prolapse-induced polyps and hyperplastic polyposis. We contribute a case of ICP from a 59-year-old woman who was affected by severe constipation and hematochezia. Numerous sessile and semipedunculated polyps were found in the colon, all with cap of whitish fibrin. Histology revealed erosion of the surface, superficial dilated crypts filled with mucoid inflammatory exudate, and minimal crypt serration, all findings typical of ICP. Only the largest polyps had smooth muscle in the mucosa. Ki-67 showed modest expansion and irregular distribution of the crypts proliferative areas. Low-degree positivity for p16, similar to that of hyperplastic polyps, was found. CK20 was expressed as in normal mucosa. Distinguishing between ICP and other polyposis is important because of difference in management. PMID:23994878

  5. Culture - colonic tissue

    MedlinePlus

    ... from the large intestine. The cause may be bacteria, fungi, or viruses. ... bacteria Cytomegalovirus Mycobacterium tuberculosis bacteria Salmonella bacteria Shigella bacteria These organisms may lead to diarrhea or infections involving the colon.

  6. Transverse colon conduit diversion

    SciTech Connect

    Schmidt, J.D.; Buchsbaum, H.J.

    1986-05-01

    The versatility and other advantages of the transverse colon conduit for urinary diversion have been described and implemented in 50 patients. Because most patients considered for this procedure will be at high risk because of a history of significant pelvic irradiation, underlying malignancy, poor renal function, fistula, and so forth, the technical details of surgery and patient selection cannot be minimized. The transverse colon segment is indicated for primary supravesical diversion as well as for salvage of problems related to ileal conduits. Adenocarcinoma of the colon is an unlikely long-term complication of this form of diversion because the fecal stream is absent. Now that the transverse colon conduit has been used for more than 10 years, meaningful comparisons with ileal segments should soon be available.

  7. [Angiodysplasia of the colon].

    PubMed

    Bruni, R; Rossodivita, I; Santoro, M; La Banca, G; Rollo, R; Putti, R

    1990-01-01

    The Authors report their experience with a case of angiodysplasia of the colon. It is outlined how these lesions can be demonstrated by angiography and colonoscopy. The pathophysiology, diagnosis and management are discussed as well. PMID:2223469

  8. Laparoscopic Colon Resection

    MedlinePlus

    ... inches to complete the procedure. What are the Advantages of Laparoscopic Colon Resection? Results may vary depending ... type of procedure and patient’s overall condition. Common advantages are: Less postoperative pain May shorten hospital stay ...

  9. Colon cancer screening

    MedlinePlus

    ... screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test ... death and complications caused by colorectal cancer. SCREENING TESTS There are several ways to screen for colon ...

  10. Intestinal colonization resistance

    PubMed Central

    Lawley, Trevor D; Walker, Alan W

    2013-01-01

    Dense, complex microbial communities, collectively termed the microbiota, occupy a diverse array of niches along the length of the mammalian intestinal tract. During health and in the absence of antibiotic exposure the microbiota can effectively inhibit colonization and overgrowth by invading microbes such as pathogens. This phenomenon is called ‘colonization resistance’ and is associated with a stable and diverse microbiota in tandem with a controlled lack of inflammation, and involves specific interactions between the mucosal immune system and the microbiota. Here we overview the microbial ecology of the healthy mammalian intestinal tract and highlight the microbe–microbe and microbe–host interactions that promote colonization resistance. Emerging themes highlight immunological (T helper type 17/regulatory T-cell balance), microbiota (diverse and abundant) and metabolic (short-chain fatty acid) signatures of intestinal health and colonization resistance. Intestinal pathogens use specific virulence factors or exploit antibiotic use to subvert colonization resistance for their own benefit by triggering inflammation to disrupt the harmony of the intestinal ecosystem. A holistic view that incorporates immunological and microbiological facets of the intestinal ecosystem should facilitate the development of immunomodulatory and microbe-modulatory therapies that promote intestinal homeostasis and colonization resistance. PMID:23240815

  11. Leptin Promotes Wound Healing in the Oral Mucosa

    PubMed Central

    Umeki, Hirochika; Tokuyama, Reiko; Ide, Shinji; Okubo, Mitsuru; Tadokoro, Susumu; Tezuka, Mitsuki; Tatehara, Seiko; Satomura, Kazuhito

    2014-01-01

    Introduction Leptin, a 16 kDa circulating anti-obesity hormone, exhibits many physiological properties. Recently, leptin was isolated from saliva; however, its function in the oral cavity is still unclear. In this study, we investigated the physiological role of leptin in the oral cavity by focusing on its effect on wound healing in the oral mucosa. Methods Immunohistochemical analysis was used to examine the expression of the leptin receptor (Ob-R) in human/rabbit oral mucosa. To investigate the effect of leptin on wound healing in the oral mucosa, chemical wounds were created in rabbit oral mucosa, and leptin was topically administered to the wound. The process of wound repair was histologically observed and quantitatively analyzed by measuring the area of ulceration and the duration required for complete healing. The effect of leptin on the proliferation, differentiation and migration of human oral mucosal epithelial cells (RT7 cells) was investigated using crystal violet staining, reverse transcription polymerase chain reaction (RT-PCR) and a wound healing assay, respectively. Results Ob-R was expressed in spinous/granular cells in the epithelial tissue and vascular endothelial cells in the subepithelial connective tissue of the oral mucosa. Topical administration of leptin significantly promoted wound healing and shortened the duration required for complete healing. Histological analysis of gingival tissue beneath the ulceration showed a denser distribution of blood vessels in the leptin-treated group. Although the proliferation and differentiation of RT7 cells were not affected by leptin, the migration of these cells was accelerated in the presence of leptin. Conclusion Topically administered leptin was shown to promote wound healing in the oral mucosa by accelerating epithelial cell migration and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound

  12. Optical properties of human colon tissues in the 350 – 2500 nm spectral range

    SciTech Connect

    Bashkatov, A N; Genina, E A; Kochubey, V I; Kolesnikova, E A; Tuchin, V V; Rubtsov, V S

    2014-08-31

    We present the optical characteristics of the mucosa and submucosa of human colon tissue. The experiments are performed in vitro using a LAMBDA 950 spectrophotometer in the 350 – 2500 nm spectral range. The absorption and scattering coefficients and the scattering anisotropy factor are calculated based on the measured diffuse reflectance and total and collimated transmittance spectra using the inverse Monte Carlo method. (laser biophotonics)

  13. Taxonomic identification of commensal bacteria associated with the mucosa and digesta throughout the gastrointestinal tracts of preweaned calves.

    PubMed

    Malmuthuge, Nilusha; Griebel, Philip J; Guan, Le Luo

    2014-03-01

    Bacterial colonization in the gastrointestinal tracts (GIT) of preweaned calves is very important, since it can influence early development and postweaning performance and health. This study investigated the composition of the bacteria along the GIT (rumen, jejunum, ileum, cecum, and colon) of preweaned bull calves (3 weeks old) using pyrosequencing to understand the segregation of bacteria between the mucosal surface and digesta. Phylogenetic analysis revealed that a total of 83 genera belonging to 13 phyla were distributed throughout the GIT of preweaned calves, with the Firmicutes, Bacteroidetes, and Proteobacteria predominating. Quantitative PCR (qPCR) analysis of selected abundant bacterial genera (Prevotella, Bacteroides, Lactobacillus, and Faecalibacterium) revealed that their prevalence was significantly different among the GIT regions and between mucosa- and digesta-associated communities. Rumens contained the most diverse bacterial population, consisting of 47 genera, including 16 rumen-specific genera, followed by the large intestine and then the small intestine. Bacterial species richness was higher at the mucosal surface than in the local digesta, with the exception of the rumen. The majority of bacteria found on the rumen epithelial surface and within the small intestine could not be identified due to a lack of known genus-level information. Thus, future studies will be required to fully characterize the microbiome during the development of the rumens and the mucosal immune systems of newborn calves. This is the first study to analyze in depth the bacterial composition of the GIT microbiome in preweaned calves, which extends previous findings regarding early rumen colonization and bacterial segregation between mucosa- and digesta-associated microbial communities. PMID:24441166

  14. Disparities of conjugating protective enzyme activities in the colon of patients with adenomas and carcinomas

    PubMed Central

    Hoensch, Harald P; Roelofs, Hennie MJ; Edler, Lutz; Kirch, Wilhelm; Peters, Wilbert HM

    2013-01-01

    AIM: To investigate the metabolic enzymatic capacity of the colon mucosa to detoxify noxious carcinogenic compounds. METHODS: We investigated the activity of 2 conjugating enzymes-the microsomal uridine glucuronosyltransferase (UGT) and the cytosomal glutathione S-transferase (GST) in the uninvolved mucosa of the colon transversum and sigmoideum in patients with adenomatous polyps and colorectal cancer. Biopsies were taken from the mucosa during colonoscopies which were done for clinical (diagnostic) reasons. After storage, the biopsy material was homogenized and after differential centrifugation the enzyme assays were performed with 4-nitrophenol (UGT) and 1-chloro 2,4-dinitrobenzene (GST) as substrates. RESULTS: About 48 patients were included of which 28 had adenomas and 20 had colorectal carcinomas confirmed by histopathology. Enzyme activities were expressed as nmol/mg per minute protein for the GST and as pmol/mg per minute protein for the UGT. Analysis of variance (F-test) indicated that both enzymes were more widely distributed in adenoma than in cancer patients. The means ± SD were smaller for cancer patients: GST for adenomas 268 ± 152 vs 241 ± 69 for carcinomas and UGT for adenomas 197 ± 200 vs 150 ± 86 for carcinomas. CONCLUSION: Compared to patients with adenomatous colon polyps those with colorectal carcinoma exhibited a lower capacity of detoxifying enzyme metabolism and their activities clustered over a smaller range. PMID:24106402

  15. Drug-induced lesions of the oesophageal mucosa.

    PubMed

    2015-09-01

    Lesions of the oesophageal mucosa are observed in various situations: most often with gastrooesophageal reflux disease, but also with infections, cancer, contact with a toxic substance, etc. When they are symptomatic, these lesions provoke burning sensations, dysphagia, regurgitation and sometimes dorsal pain. The changes to the oesophageal mucosa may take various forms: inflammation, erosion, ulceration or necrosis. Serious or even fatal complications can develop but are rare; they include oesophageal perforation, stricture and haemorrhage. Some oral drugs damage the oesophageal mucosa through direct contact. The symptoms often develop several hours after ingestion. The pain is of sudden onset. The resulting lesions are solitary or multiple ulcers that vary in depth and usually occur in the upper portion of the oesophagus. Various factors prolong contact between a drug and the oesophageal mucosa, in particular: swallowing the drug with insufficient liquid or just before lying down; capsule forms; and oesophageal abnormalities. The drugs most frequently implicated are tetracyclines, particularly doxycycline, bisphosphonates and various nonsteroidal anti-inflammatory drugs (NSAIDs). Many drugs, used in various situations, provoke gastro-oesophageal reflux disease, sometimes causing mucosal lesions in the lower oesophagus: calcium-channel blockers, nitrates, exenatide and liraglutide, drugs with antimuscarinic effects, theophylline, etc. Some drugs affect all mucous membranes in the body, including the oesophageal mucosa, irrespective of their route of administration: cancer drugs, isotretinoin, and nicorandil. PMID:26417631

  16. Cleft palate cells can regenerate a palatal mucosa in vitro.

    PubMed

    Liu, J; Lamme, E N; Steegers-Theunissen, R P M; Krapels, I P C; Bian, Z; Marres, H; Spauwen, P H M; Kuijpers-Jagtman, A M; Von den Hoff, J W

    2008-08-01

    Cleft palate repair leaves full-thickness mucosal defects on the palate. Healing might be improved by implantation of a mucosal substitute. However, the genetic and phenotypic deviations of cleft palate cells may hamper tissue engineering. The aim of this study was to construct mucosal substitutes from cleft palate cells, and to compare these with substitutes from normal palatal cells, and with native palatal mucosa. Biopsies from the palatal mucosa of eight children with cleft palate and eight age-matched control individuals were taken. Three biopsies of both groups were processed for (immuno)histochemistry; 5 were used to culture mucosal substitutes. Histology showed that the substitutes from cleft-palate and non-cleft-palate cells were comparable, but the number of cell layers was less than in native palatal mucosa. All epithelial layers in native palatal mucosa and mucosal substitutes expressed the cytokeratins 5, 10, and 16, and the proliferation marker Ki67. Heparan sulphate and decorin were present in the basal membrane and the underlying connective tissue, respectively. We conclude that mucosal cells from children with cleft palate can regenerate an oral mucosa in vitro. PMID:18650554

  17. Glycoprotein expression by adenomatous polyps of the colon

    NASA Astrophysics Data System (ADS)

    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.

  18. MicroRNA-193a-3p Reduces Intestinal Inflammation in Response to Microbiota via Down-regulation of Colonic PepT1.

    PubMed

    Dai, Xin; Chen, Xi; Chen, Qun; Shi, Lei; Liang, Hongwei; Zhou, Zhen; Liu, Qian; Pang, Wenjing; Hou, Dongxia; Wang, Cheng; Zen, Ke; Yuan, Yaozong; Zhang, Chen-Yu; Xia, Lu

    2015-06-26

    Intestinal inflammation is characterized by epithelial disruption, leading to the loss of barrier function, recruitment of immune cells, and host immune responses to gut microbiota. PepT1, a di/tripeptide transporter that uptakes bacterial products, is up-regulated in inflamed colon tissue, which implies its role in bacterium-associated intestinal inflammation. Although microRNA (miRNA)-mediated gene regulation has been found to be involved in various processes of inflammatory bowel disease (IBD), the biological function of miRNAs in the pathogenesis of IBD remains to be explored. In this study we detected miRNA expression patterns in colon tissues during colitis and investigated the mechanism underlying the regulation of colonic PepT1 by miRNAs. We observed an inverse correlation between PepT1 and miR-193a-3p in inflamed colon tissues with active ulcerative colitis, and we further demonstrated that miR-193a-3p reduced PepT1 expression and activity as a target gene and subsequently suppressed the NF-κB pathway. Intracolonic delivery of miR-193a-3p significantly ameliorated dextran sodium sulfate-induced colitis, whereas the overexpression of colonic PepT1 via PepT1 3'-untranslated region mutant lentivirus vector abolished the anti-inflammatory effect of miR-193a-3p. Furthermore, antibiotic treatment eliminated the difference in the dextran sodium sulfate-induced inflammation between the presence and absence of miR-193a-3p. These findings suggest that miR-193a-3p regulation of PepT1 mediates the uptake of bacterial products and is a potent mechanism during the colonic inflammation process. Overall, we believe miR-193a-3p may be a potent regulator of colonic PepT1 for maintaining intestinal homeostasis. PMID:25931122

  19. Candida albicans Ultrastructure: Colonization and Invasion of Oral Epithelium

    PubMed Central

    Howlett, Julie A.; Squier, Christopher A.

    1980-01-01

    The colonization and invasion of various animal oral mucosae by Candida albicans were examined in an organ culture model. Scanning and transmission electron microscopy of the oral epithelium between 12 and 30 h after inoculation with the fungus revealed the morphological relationships between host and parasite. Examination of the fungi in thin sections showed five distinct layers in the cell wall of C. albicans within the epithelium, but changes were evident in the organization and definition of the outer cell wall layers in budding hyphae and in hyphae participating in colonization and invasion of the epithelial cells. Adherence of the fungus to the superficial cells of the oral mucosa appeared to involve intimate contact between the epithelial cell surface and the deeper layers of the fungal cell wall. During invasion a close seal was maintained between the invading hyphae and the surrounding epithelial cell envelope, there being no other evidence of damage to the host cell surface except at the site of entry. Within the epithelial cells there was only occasional loss of cytoplasmic components in the vicinity of the invading hyphae. These findings would suggest that enzymatic lysis associated with the invasive process is localized and that the mechanical support provided by surface adherence and the intimate association between the fungus and the epithelial cell envelope may permit growth of Candida on through the epithelium. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:6995338

  20. A recellularized human colon model identifies cancer driver genes.

    PubMed

    Chen, Huanhuan Joyce; Wei, Zhubo; Sun, Jian; Bhattacharya, Asmita; Savage, David J; Serda, Rita; Mackeyev, Yuri; Curley, Steven A; Bu, Pengcheng; Wang, Lihua; Chen, Shuibing; Cohen-Gould, Leona; Huang, Emina; Shen, Xiling; Lipkin, Steven M; Copeland, Neal G; Jenkins, Nancy A; Shuler, Michael L

    2016-08-01

    Refined cancer models are needed to bridge the gaps between cell line, animal and clinical research. Here we describe the engineering of an organotypic colon cancer model by recellularization of a native human matrix that contains cell-populated mucosa and an intact muscularis mucosa layer. This ex vivo system recapitulates the pathophysiological progression from APC-mutant neoplasia to submucosal invasive tumor. We used it to perform a Sleeping Beauty transposon mutagenesis screen to identify genes that cooperate with mutant APC in driving invasive neoplasia. We identified 38 candidate invasion-driver genes, 17 of which, including TCF7L2, TWIST2, MSH2, DCC, EPHB1 and EPHB2 have been previously implicated in colorectal cancer progression. Six invasion-driver genes that have not, to our knowledge, been previously described were validated in vitro using cell proliferation, migration and invasion assays and ex vivo using recellularized human colon. These results demonstrate the utility of our organoid model for studying cancer biology. PMID:27398792

  1. Bioimage analysis of Shigella infection reveals targeting of colonic crypts

    PubMed Central

    Arena, Ellen T.; Campbell-Valois, Francois-Xavier; Tinevez, Jean-Yves; Nigro, Giulia; Sachse, Martin; Moya-Nilges, Maryse; Nothelfer, Katharina; Marteyn, Benoit; Shorte, Spencer L.; Sansonetti, Philippe J.

    2015-01-01

    Few studies within the pathogenic field have used advanced imaging and analytical tools to quantitatively measure pathogenicity in vivo. In this work, we present a novel approach for the investigation of host–pathogen processes based on medium-throughput 3D fluorescence imaging. The guinea pig model for Shigella flexneri invasion of the colonic mucosa was used to monitor the infectious process over time with GFP-expressing S. flexneri. A precise quantitative imaging protocol was devised to follow individual S. flexneri in a large tissue volume. An extensive dataset of confocal images was obtained and processed to extract specific quantitative information regarding the progression of S. flexneri infection in an unbiased and exhaustive manner. Specific parameters included the analysis of S. flexneri positions relative to the epithelial surface, S. flexneri density within the tissue, and volume of tissue destruction. In particular, at early time points, there was a clear association of S. flexneri with crypts, key morphological features of the colonic mucosa. Numerical simulations based on random bacterial entry confirmed the bias of experimentally measured S. flexneri for early crypt targeting. The application of a correlative light and electron microscopy technique adapted for thick tissue samples further confirmed the location of S. flexneri within colonocytes at the mouth of crypts. This quantitative imaging approach is a novel means to examine host–pathogen systems in a tailored and robust manner, inclusive of the infectious agent. PMID:26056271

  2. Bioimage analysis of Shigella infection reveals targeting of colonic crypts.

    PubMed

    Arena, Ellen T; Campbell-Valois, Francois-Xavier; Tinevez, Jean-Yves; Nigro, Giulia; Sachse, Martin; Moya-Nilges, Maryse; Nothelfer, Katharina; Marteyn, Benoit; Shorte, Spencer L; Sansonetti, Philippe J

    2015-06-23

    Few studies within the pathogenic field have used advanced imaging and analytical tools to quantitatively measure pathogenicity in vivo. In this work, we present a novel approach for the investigation of host-pathogen processes based on medium-throughput 3D fluorescence imaging. The guinea pig model for Shigella flexneri invasion of the colonic mucosa was used to monitor the infectious process over time with GFP-expressing S. flexneri. A precise quantitative imaging protocol was devised to follow individual S. flexneri in a large tissue volume. An extensive dataset of confocal images was obtained and processed to extract specific quantitative information regarding the progression of S. flexneri infection in an unbiased and exhaustive manner. Specific parameters included the analysis of S. flexneri positions relative to the epithelial surface, S. flexneri density within the tissue, and volume of tissue destruction. In particular, at early time points, there was a clear association of S. flexneri with crypts, key morphological features of the colonic mucosa. Numerical simulations based on random bacterial entry confirmed the bias of experimentally measured S. flexneri for early crypt targeting. The application of a correlative light and electron microscopy technique adapted for thick tissue samples further confirmed the location of S. flexneri within colonocytes at the mouth of crypts. This quantitative imaging approach is a novel means to examine host-pathogen systems in a tailored and robust manner, inclusive of the infectious agent. PMID:26056271

  3. Implications of the colonic deposition of free hemoglobin-alpha chain: a previously unknown tissue by-product in inflammatory bowel disease

    PubMed Central

    Myers, Jeremy N.; Schäffer, Michael W.; Korolkova, Olga Y.; Williams, Amanda D.; Gangula, Pandu R.; M’Koma, Amosy E.

    2014-01-01

    Purpose We analyzed inflamed mucosal/submucosal layers of ulcerative colitis (UC=63) and Crohn’s colitis (CC=50) and unexpectedly we unveiled a pool of free-hemoglobin-alpha (Hb-α) chain. Patients with colitides have increased ROS, DNA-oxidation products, free-iron in mucosa, in pre-neoplastic, and in colitis-cancers and increased risks of developing colorectal-cancer (CRC). All IBD-related-CRC lesions are found in segments with colitis. Linking this information we investigated whether free-Hb-α is key transformational stepping that increases colitis-related-CRC vulnerability. Methods UC/CC samples were profiled using MALDI-MS; protein identification was made by LCM. Diverticulitis (DV) was used as control (Ctrl). The presence of Hb(n) (n=α, β and hemin)/Hb was validated by Western blotting (WB) and immunohistochemistry (IHC). We tested for DNA-damage (DNAD) by exposing normal colonic-epithelial-cell-line, NCM460, to 10μM and 100μM of Hb(n)/Hb, individually for 2 h, 6 h, and 12 h. Quantification of Hb-α-staining was done by Nikon Elements Advance Research Analysis software. ROS was measured by the production of 8-OHdG. DNAD was assessed by Comet-assay. Colonic tissue homogenate antioxidants Nrf2-, CAT-, SOD- and GPx-expressions was analyzed densitometrically/ normalized by β-actin. Results IHC of CC/UC mucosal/submucosal-compartments stained strongly positive for Hb-α and significantly higher vs. Ctrl. NCM460 exposed to Hb(n)/Hb exhibited steadily-increasing ROS and subsequent DNAD. DNAD was higher in 10μM than 100μM in Hb-β/hemin the first 2 h then plateaued followed by DNAD-repair. This may be likely due to apoptosis in the later concentration. Nrf2 enzyme activities among UC, CC and UCAC were observed impaired in all IBD subjects. Decreased levels of Nrf2 among UC vs. CC patients with active disease was insignificant as well as vs. Ctrls but significantly lower in UCAC vs. Ctrl. SOD was decreased in UC and UCAC and GPx in CC but statistically not

  4. MiR-9, -31, and -182 Deregulation Promote Proliferation and Tumor Cell Survival in Colon Cancer12

    PubMed Central

    Cekaite, Lina; Rantala, Juha K; Bruun, Jarle; Guriby, Marianne; Ågesen, Trude H; Danielsen, Stine A; Lind, Guro E; Nesbakken, Arild; Kallioniemi, Olli; Lothe, Ragnhild A; Skotheim, Rolf I

    2012-01-01

    Several microRNAs (miRNAs) are known to be deregulated in colon cancer, but the mechanisms behind their potential involvement on proliferation and tumor cell survival are unclear. The present study aimed to identify miRNAs with functional implications for development of colon cancer. The cell proliferation and apoptosis were examined following perturbations of miRNA levels by employing a comprehensive miRNA library screen. miRNAs nominated for relevance to colon cancer were validated on expression and functional levels. By integrating the effect of miRNA up-regulation with the endogenous miRNA expression levels within the HT29, HCT116, and SW480 colon cancer cell lines, we identified miRNAs controlling cell proliferation (n = 53) and apoptosis (n = 93). From these functionally nominated miRNAs, we narrowed the list to 10 oncogene- and 20 tumor suppressor-like miRNAs that were also differentially expressed between colon cancer (n = 80) and normal colonic mucosa (n = 20). The differential expressions of miR-9, miR-31, and miR-182 were successfully validated in a series of colon carcinomas (n = 30) and polyps (n = 10) versus normal colonic mucosa (n = 10), whereas the functional effect was confirmed in an in-depth validation using different cell viability and apoptotic markers. Several transcription factors and genes regulating cell proliferation were identified as putative target genes by integrative miRNA/mRNA expression analysis obtained from the same colon cancer patient samples. This study suggests that deregulated expression of miR-9, miR-31, and miR-182 during carcinogenesis plays a significant role in the development of colon cancer by promoting proliferation and tumor cell survival. PMID:23019418

  5. Advances in understanding colonic function.

    PubMed

    Milla, Peter J

    2009-04-01

    The colon is an organ of conservation that salvages water, electrolytes, and energy. The organization of colonic function is determined by the roles played by the luminal flora, the function of the different mucosal epithelial cell types, immunocompetent cells, and the neuromusculature. These different components of the colon interact with one another and with the colonic flora, and different areas of the colon serve different functions. In the normal adult during the course of a day the colon absorbs approximately 1.5 L of fluid, but under the influence of aldosterone increases up to 5 to 6 L. Diarrhoea occurs when secretion exceeds absorptive processes by either small intestinal secretion overwhelming colonic salvage or salvage being impaired by reduced colonic absorption or increased colonic secretion. PMID:19300122

  6. Novel aspects of cholinergic regulation of colonic ion transport.

    PubMed

    Bader, Sandra; Diener, Martin

    2015-06-01

    Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiments with putative nicotinic agonists and antagonists were performed at rat colon combined with reverse transcription polymerase chain reaction (RT-PCR) detection of nicotinic receptor subunits within the epithelium. Dimethylphenylpiperazinium (DMPP) and nicotine induced a tetrodotoxin-resistant anion secretion leading to an increase in short-circuit current (I sc) across colonic mucosa. The response was suppressed by the nicotinic receptor antagonist hexamethonium. RT-PCR experiments revealed the expression of α2, α4, α5, α6, α7, α10, and β4 nicotinic receptor subunits in colonic epithelium. Choline, the product of acetylcholine hydrolysis, is known for its affinity to several nicotinic receptor subtypes. As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on I sc was examined. Choline induced a concentration-dependent, tetrodotoxin-resistant chloride secretion which was, however, resistant against hexamethonium, but was inhibited by atropine. Experiments with inhibitors of muscarinic M1 and M3 receptors revealed that choline-evoked secretion was mainly due to a stimulation of epithelial M3 receptors. Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion. Thus the cholinergic regulation of colonic ion transport - up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors - is more complex than previously assumed. PMID:26236483

  7. Novel aspects of cholinergic regulation of colonic ion transport

    PubMed Central

    Bader, Sandra; Diener, Martin

    2015-01-01

    Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiments with putative nicotinic agonists and antagonists were performed at rat colon combined with reverse transcription polymerase chain reaction (RT-PCR) detection of nicotinic receptor subunits within the epithelium. Dimethylphenylpiperazinium (DMPP) and nicotine induced a tetrodotoxin-resistant anion secretion leading to an increase in short-circuit current (Isc) across colonic mucosa. The response was suppressed by the nicotinic receptor antagonist hexamethonium. RT-PCR experiments revealed the expression of α2, α4, α5, α6, α7, α10, and β4 nicotinic receptor subunits in colonic epithelium. Choline, the product of acetylcholine hydrolysis, is known for its affinity to several nicotinic receptor subtypes. As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on Isc was examined. Choline induced a concentration-dependent, tetrodotoxin-resistant chloride secretion which was, however, resistant against hexamethonium, but was inhibited by atropine. Experiments with inhibitors of muscarinic M1 and M3 receptors revealed that choline-evoked secretion was mainly due to a stimulation of epithelial M3 receptors. Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion. Thus the cholinergic regulation of colonic ion transport – up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors – is more complex than previously assumed. PMID:26236483

  8. Mast Cells Infiltrating Inflamed or Transformed Gut Alternatively Sustain Mucosal Healing or Tumor Growth.

    PubMed

    Rigoni, Alice; Bongiovanni, Lucia; Burocchi, Alessia; Sangaletti, Sabina; Danelli, Luca; Guarnotta, Carla; Lewis, Amy; Rizzo, Aroldo; Silver, Andrew R; Tripodo, Claudio; Colombo, Mario P

    2015-09-15

    Mast cells (MC) are immune cells located next to the intestinal epithelium with regulatory function in maintaining the homeostasis of the mucosal barrier. We have investigated MC activities in colon inflammation and cancer in mice either wild-type (WT) or MC-deficient (Kit(W-sh)) reconstituted or not with bone marrow-derived MCs. Colitis was chemically induced with dextran sodium sulfate (DSS). Tumors were induced by administering azoxymethane (AOM) intraperitoneally before DSS. Following DSS withdrawal, Kit(W-sh) mice showed reduced weight gain and impaired tissue repair compared with their WT littermates or Kit(W-sh) mice reconstituted with bone marrow-derived MCs. MCs were localized in areas of mucosal healing rather than damaged areas where they degraded IL33, an alarmin released by epithelial cells during tissue damage. Kit(W-sh) mice reconstituted with MC deficient for mouse mast cell protease 4 did not restore normal mucosal healing or reduce efficiently inflammation after DSS withdrawal. In contrast with MCs recruited during inflammation-associated wound healing, MCs adjacent to transformed epithelial cells acquired a protumorigenic profile. In AOM- and DSS-treated WT mice, high MC density correlated with high-grade carcinomas. In similarly treated Kit(W-sh) mice, tumors were less extended and displayed lower histologic grade. Our results indicate that the interaction of MCs with epithelial cells is dependent on the inflammatory stage, and on the activation of the tissue repair program. Selective targeting of MCs for prevention or treatment of inflammation-associated colon cancer should be timely pondered to allow tissue repair at premalignant stages or to reduce aggressiveness at the tumor stage. PMID:26206557

  9. Histochemical study of the olfactory mucosae of the horse.

    PubMed

    Lee, Kwang-Hyup; Park, Changnam; Bang, Hyojin; Ahn, Meejung; Moon, Changjong; Kim, Seungjoon; Shin, Taekyun

    2016-05-01

    The olfactory mucosae of the horse were examined by using histology and lectin histochemistry to characterize the carbohydrate sugar residues therein. Histological findings revealed that olfactory epithelium (OE) consisted of both olfactory marker protein (OMP)- and protein gene product (PGP) 9.5-positive receptor cells, supporting cells and basal cells with intervening secretory ducts from Bowman's glands. Mucus histochemistry showed that Bowman's gland acini contain periodic acid-Schiff (PAS) reagent-positive neutral mucins and alcian blue pH 2.5-positive mucosubstances. Lectin histochemistry revealed that a variety of carbohydrate sugar residues, including N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, fucose and complex type N-glycan groups, are present in the various cell types in the olfactory mucosa at varying levels. Collectively, this is the first descriptive study of horse olfactory mucosa to characterize carbohydrate sugar residues in the OE and Bowman's glands. PMID:27040092

  10. Harvesting oral mucosa for one-stage anterior urethroplasty

    PubMed Central

    Kulkarni, Sanjay Balwant; Barbagli, Guido; Sansalone, Salvatore; Joshi, Pankaj Mangalkumar

    2014-01-01

    Oral mucosa has been the most popular substitute material for urethral reconstructive surgery because it is easy to harvest, is easy to access, has a concealed donor site scar, and obviates most of the problems associated with other grafts. However, the success of using oral mucosa for urethral surgery is mainly attributed to the biological properties of this tissue. Herein, the surgical steps of harvesting oral mucosa from the inner cheek are presented with an emphasis on tips and tricks to render the process easier and more reproducible and to prevent intra and post-operative complications. The following steps are emphasized: Nasal intubation, ovoid shape graft, delicate harvesting leaving the muscle intact, donor site closure and removal of submucosal tissue. PMID:24497698

  11. Buccal mucosa ridging and tongue indentation: incidence and associated factors.

    PubMed

    Piquero, K; Ando, T; Sakurai, K

    1999-05-01

    Buccal mucosa ridging and tongue indentation have been considered as one of the visible and reliable signs of bruxism. However, there have not been any reports justifying this relationship scientifically. Moreover, there have not been any studies reporting specific procedures to assess them. Thus, the purpose of the present study was to determine the clinical incidence of buccal mucosa ridging and tongue indentation and assess the possible relationship between certain factors that can influence their occurrence. A total of 244 (178 males and 66 females) dentulous adults from 20 to 59 years of age, who were employees at the Bank of Yokohama, were randomly selected. At first, the buccal mucosa ridging and tongue indentation were classified into three groups based in their intensity: none, mild, and severe. The incidence of both conditions in the different age groups, as well as the incidence by gender was evaluated. Furthermore, the possible relationships between buccal mucosa ridging and tongue indentation and age, gender, clenching awareness, grinding awareness, headache, neck stiffness, vertical dimension, temporomandibular joint (TMJ) pain to palpation, masticatory muscle tenderness to palpation, and the presence of premature contacts were evaluated using the chi-square test. A positive relationship was found between the occurrence of buccal mucosa ridging and tongue indentation and gender (p < 0.01); both conditions were observed more frequently in females than in males. A positive relationship was also found to age; the group between 20-29 years old showed the highest incidence. The vertical dimension had a positive relationship with the occurrence of both buccal mucosa ridging and tongue indentation. Other factors evaluated did not show any correlation. PMID:10825817

  12. Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

    PubMed Central

    Coppedè, Fabio; Migheli, Francesca; Lopomo, Angela; Failli, Alessandra; Legitimo, Annalisa; Consolini, Rita; Fontanini, Gabriella; Sensi, Elisa; Servadio, Adele; Seccia, Massimo; Zocco, Giuseppe; Chiarugi, Massimo; Spisni, Roberto; Migliore, Lucia

    2014-01-01

    We evaluated the promoter methylation levels of the APC, MGMT, hMLH1, RASSF1A and CDKN2A genes in 107 colorectal cancer (CRC) samples and 80 healthy adjacent tissues. We searched for correlation with both physical and pathological features, polymorphisms of folate metabolism pathway genes (MTHFR, MTRR, MTR, RFC1, TYMS, and DNMT3B), and data on circulating folate, vitamin B12 and homocysteine, which were available in a subgroup of the CRC patients. An increased number of methylated samples were found in CRC respect to adjacent healthy tissues, with the exception of APC, which was also frequently methylated in healthy colonic mucosa. Statistically significant associations were found between RASSF1A promoter methylation and tumor stage, and between hMLH1 promoter methylation and tumor location. Increasing age positively correlated with both hMLH1 and MGMT methylation levels in CRC tissues, and with APC methylation levels in the adjacent healthy mucosa. Concerning gender, females showed higher hMLH1 promoter methylation levels with respect to males. In CRC samples, the MTR 2756AG genotype correlated with higher methylation levels of RASSF1A, and the TYMS 1494 6bp ins/del polymorphism correlated with the methylation levels of both APC and hMLH1. In adjacent healthy tissues, MTR 2756AG and TYMS 1494 6bp del/del genotypes correlated with APC and MGMT promoter methylation, respectively. Low folate levels were associated with hMLH1 hypermethylation. Present results support the hypothesis that DNA methylation in CRC depends from both physiological and environmental factors, with one-carbon metabolism largely involved in this process. PMID:24500500

  13. Dichotomous Metabolism of Enterococcus faecalis Induced by Hematin Starvation Modulates Colonic Gene Expression

    PubMed Central

    Allen, Toby D.; Moore, Danny R.; Wang, Xingmin; Casu, Viviana; May, Randal; Lerner, Megan R.; Houchen, Courtney; Brackett, Daniel J.; Huycke, Mark M.

    2009-01-01

    Summary Enterococcus faecalis is an intestinal commensal that cannot synthesize porphyrins and only expresses a functional respiratory chain when provided exogenous hematin. In the absence of hematin, E. faecalis reverts to fermentative metabolism and produces extracellular superoxide that can damage epithelial cell DNA. The acute response of the colonic mucosa to hematin-starved E. faecalis was identified by gene array. E. faecalis was inoculated into murine colons using a surgical ligation model that preserved tissue architecture and homeostasis. The mucosa was exposed to hematin-starved E. faecalis and compared to a control consisting of the same strain grown with hematin. At 1 hour post-inoculation six mucosal genes were differentially regulated and this increased to 42 genes at 6 hours. At 6 hours a highly significant biological interaction network was identified with functions that included NF-κB signaling, apoptosis, and cell cycle regulation. Colon biopsies showed no histological abnormalities by hematoxylin and eosin staining. Immunohistochemical staining, however, detected NF-κB activation in tissue macrophages using antibodies to the nuclear localization sequence for p65 and the F4/80 marker for murine macrophages. Similarly, hematin-starved E. faecalis strongly activated NF-κB in murine macrophages in vitro. Furthermore, primary and transformed colonic epithelial cells activated the G2/M checkpoint in vitro following exposure to hematin-starved E. faecalis. Modulation of this cell cycle checkpoint was due to extracellular superoxide produced as a result of the respiratory block in hematin-starved E. faecalis. These results demonstrate that the uniquely dichotomous metabolism of E. faecalis can significantly modulate gene expression in the colonic mucosa for pathways associated with inflammation, apoptosis, and cell cycle regulation. PMID:18809545

  14. Oral focal mucinosis of palatal mucosa: A rare case report

    PubMed Central

    Bharti, Vipin; Singh, Jagmohan

    2012-01-01

    Oral focal mucinosis (OFM), an oral counterpart of cutaneous focal mucinosis, is a rare disease of unknown etiology. Its pathogenesis may be due to the overproduction of hyaluronic acid by a fibroblast, at the expense of collagen production, resulting in focal myxoid degeneration of the connective tissue, primarily affecting the mucosa overlying the bone. It has no distinctive clinical features, as the diagnosis is solely based on the histopathological features. This article reports of a 32-year-old female having the rare disease of oral focal mucinosis, involving the posterior palatal mucosa, and discusses its clinicopathological features and differential diagnosis of myxomatous lesions of the oral cavity. PMID:23230367

  15. Respiratory burst activity of intestinal macrophages in normal and inflammatory bowel disease.

    PubMed Central

    Mahida, Y R; Wu, K C; Jewell, D P

    1989-01-01

    Macrophages isolated from normal mucosa (greater than 5 cm from tumour) and inflamed mucosa (from patients with inflammatory bowel disease) of colon and ileum were studied for their ability to undergo a respiratory burst as assessed by reduction of nitroblue tetrazolium to formazan. Using phorbol myristate acetate (PMA) and opsonised zymosan as triggers, only a minority (median: 8% for zymosan and 9% for PMA) of macrophages isolated from normal colonic mucosa demonstrated release of oxygen radicals. In contrast, a significantly greater (median: 17% for zymosan and 45% for PMA) proportion of macrophages isolated from inflamed colonic mucosa were able to undergo respiratory burst. Studies with normal and inflamed ileum showed similar results. Stimulation of macrophages isolated from normal colon with interferon-gamma produced only a small increase in the proportion of cells showing release of oxygen radicals. We conclude that the respiratory burst capacity of majority of macrophages isolated from normal colon and ileum is downregulated and a greater proportion of macrophages isolated from inflamed colon and ileum are able to undergo a respiratory burst. Images Fig. 2 PMID:2511088

  16. Fecal levels of short-chain fatty acids and bile acids as determinants of colonic mucosal cell proliferation in humans.

    PubMed

    Dolara, Piero; Caderni, Giovanna; Salvadori, Maddalena; Morozzi, Guido; Fabiani, Roberto; Cresci, Alberto; Orpianesi, Carla; Trallori, Giacomo; Russo, Antonio; Palli, Domenico

    2002-01-01

    We studied the correlation between fecal levels of short-chain fatty acids (SCFA), bile acids (BA), and colonic mucosal proliferation in humans on a free diet. Subjects [n = 43: 27 men and 16 women; 61 +/- 7 and 59 +/- 6 (SE) yr old, respectively] were outpatients who previously underwent resection of at least two sporadic colon polyps. Mucosal proliferation was determined by [3H]thymidine incorporation in vitro in three colorectal biopsies obtained without cathartics and was expressed as labeling index (LI). BA were analyzed in feces by mass spectrometry and SCFA by gas chromatography. We found that increasing levels of BA in feces did not correlate with higher LI. On the contrary, higher levels of SCFA were significantly associated with lower LI in the colonic mucosa (P for trend = 0.02). In conclusion, in humans on a free diet, intestinal proliferation seems to be regulated by the levels of SCFA in feces and not by BA. Because a lower intestinal proliferation is associated with a decreased colon cancer risk, treatments or diets that increase colonic levels of SCFA might be beneficial for colonic mucosa. PMID:12416258

  17. [Intestinal occlusion due to pancreatitis mimicking stenosing neoplasm of the splenic angle of the colon].

    PubMed

    Pascual, M; Pera, M; Martínez, I; Miquel, R; Grande, L

    2005-01-01

    Colonic involvement in patients with severe acute pancreatitis or chronic pancreatitis is common and complications such as paralytic ileus, segmental necrosis and pancreatic-colonic fistulae have been described. However, mechanical occlusion of the colon due to pancreatitis is infrequent. We present the case of a 45-year-old man with occlusion of the colon secondary to asymptomatic pancreatitis mimicking a locally advanced stenosing neoplasm of the splenic angle. Ten years prior to the present episode the patient had presented acute alcoholic pancreatitis complicated by a pseudocyst requiring surgery. The current reason for admission was abdominal colic pain and constipation with onset 5 days previously. Contrast enema was administered showing colonic occlusion caused by stenosis at the splenic flexure, suggesting the presence of a neoplasm. Urgent laparotomy showed the presence of a tumor originating in the colon that infiltrated the splenic hilum. Subtotal colectomy and en-bloc splenectomy were performed. Histopathological analysis showed pericolonic inflammation and fibrosis secondary to pancreatitis; the colonic mucosa showed no tumoral infiltration. To date, fewer than 30 cases of this infrequent complication have been published. PMID:15989813

  18. Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization.

    PubMed

    Hotomi, Muneki; Yuasa, Jun; Briles, David E; Yamanaka, Noboru

    2016-09-01

    Nasopharyngeal colonization by Streptococcus pneumoniae is an important initial step for the subsequent development of pneumococcal infections. Pneumococci have many virulence factors that play a role in colonization. Pneumolysin (PLY), a pivotal pneumococcal virulence factor for invasive disease, causes severe tissue damage and inflammation with disruption of epithelial tight junctions. In this study, we evaluated the role of PLY in nasal colonization of S. pneumoniae using a mouse colonization model. A reduction of numbers of PLY-deficient pneumococci recovered from nasal tissue, as well as nasal wash, was observed at days 1 and 2 post-intranasal challenges, but not later. The findings strongly support an important role for PLY in the initial establishment nasal colonization. PLY-dependent invasion of local nasal mucosa may be required to establish nasal colonization with S. pneumoniae. The data help provide a rationale to explain why an organism that exists as an asymptomatic colonizer has evolved virulence factors that enable it to occasionally invade and kill its hosts. Thus, the same pneumococcal virulence factor, PLY that can contribute to killing the host, may also play a role early in the establishment of nasopharynx carriage. PMID:26803756

  19. Oral Typhoid Vaccination With Live-Attenuated Salmonella Typhi Strain Ty21a Generates Ty21a-Responsive and Heterologous Influenza Virus–Responsive CD4+ and CD8+ T Cells at the Human Intestinal Mucosa

    PubMed Central

    Pennington, Shaun H.; Thompson, Ameeka L.; Wright, Adam K. A.; Ferreira, Daniela M.; Jambo, Kondwani C.; Wright, Angela D.; Faragher, Brian; Gilmour, Jill W.; Gordon, Stephen B.; Gordon, Melita A.

    2016-01-01

    Background. Oral vaccination with live-attenuated Salmonella Typhi strain Ty21a is modestly efficacious, but the mechanisms of protection are currently unknown. While humoral and cellular immune responses are well described in peripheral blood, the cellular response at the intestinal mucosa has never been directly assessed. Methods. We vaccinated healthy adults with Ty21a and assessed humoral and cellular immunity in vaccinated volunteers and controls after 18 days. Immunoglobulin levels were assessed in peripheral blood by an enzyme-linked immunosorbent assay. Cellular responses were assessed in peripheral blood and at the duodenal and colonic mucosa by flow cytometry. Results. We demonstrate the generation of Ty21a-responsive and heterologous influenza virus–responsive CD4+ and CD8+ T cells at the duodenal mucosa. All duodenal responses were consistently correlated, and no responses were observed at the colonic mucosa. Peripheral anti-lipopolysaccharide immunoglobulin G and immunoglobulin A responses were significantly correlated with duodenal responses. The assessment of integrin β7 expression intensity among peripheral and duodenal T-cell subsets revealed varied capacities for mucosal homing and residence. Conclusions. The breadth of duodenal cellular responses was not reflected peripherally. The direct evaluation of mucosal immune defense may yield functional correlates of protection and could provide insight into mechanisms that may be manipulated to enhance vaccine immunogenicity. PMID:26810369

  20. Colonization, mouse-style

    PubMed Central

    2010-01-01

    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 PMID:20977781

  1. Serotonin and colonic motility.

    PubMed

    Kendig, D M; Grider, J R

    2015-07-01

    The role of serotonin (5-hydroxytryptamine [5-HT]) in gastrointestinal motility has been studied for over 50 years. Most of the 5-HT in the body resides in the gut wall, where it is located in subsets of mucosal cells (enterochromaffin cells) and neurons (descending interneurons). Many studies suggest that 5-HT is important to normal and dysfunctional gut motility and drugs affecting 5-HT receptors, especially 5-HT3 and 5-HT4 receptors, have been used clinically to treat motility disorders; however, cardiovascular side effects have limited the use of these drugs. Recently studies have questioned the importance and necessity of 5-HT in general and mucosal 5-HT in particular for colonic motility. Recent evidence suggests the importance of 5-HT3 and 5-HT4 receptors for initiation and generation of one of the key colonic motility patterns, the colonic migrating motor complex (CMMC), in rat. The findings suggest that 5-HT3 and 5-HT4 receptors are differentially involved in two different types of rat CMMCs: the long distance contraction (LDC) and the rhythmic propulsive motor complex (RPMC). The understanding of the role of serotonin in colonic motility has been influenced by the specific motility pattern(s) studied, the stimulus used to initiate the motility (spontaneous vs induced), and the route of administration of drugs. All of these considerations contribute to the understanding and the controversy that continues to surround the role of serotonin in the gut. PMID:26095115

  2. Micro- and Nanosized Particles in Nasal Mucosa: A Pilot Study

    PubMed Central

    2015-01-01

    Objective. The aim of this prospective study is to evaluate presence and quantity of micro- and nanosized particles (NPs) and interindividual differences in their distribution and composition in nasal mucosa. Methods. Six samples of nasal mucosa obtained by mucotomy from patients with chronic hypertrophic rhinosinusitis were examined. Samples divided into 4 parts according to the distance from the nostrils were analyzed by scanning electron microscopy and Raman microspectroscopy to detect solid particles and characterize their morphology and composition. A novel method of quantification of the particles was designed and used to evaluate interindividual differences in distribution of the particles. The findings were compared with patients' employment history. Results. In all the samples, NPs of different elemental composition were found (iron, barium, copper, titanium, etc.), predominantly in the parts most distant from nostrils, in various depths from the surface of the mucosa and interindividual differences in their quantity and composition were found, possibly in relation to professional exposition. Conclusions. This study has proven the possibility of quantification of distribution of micro- and nanosized particles in tissue samples and that the NPs may deposit in deeper layers of mucosa and their elemental composition may be related to professional exposition to the sources of NPs. PMID:26125023

  3. MAGE-A antigens in lesions of the oral mucosa.

    PubMed

    Krauss, Eva; Rauthe, Stephan; Gattenlöhner, Stefan; Reuther, Tobias; Kochel, Michael; Kriegebaum, Ulrike; Kübler, Alexander C; Müller-Richter, Urs D A

    2011-06-01

    Oral squamous cell carcinoma develops continuously out of predamaged oral mucosa. For the physician and pathologist, difficulties arise in distinguishing precancerous from cancerous lesions. MAGE-A antigens are tumor antigens that are found solely in malignant transformed cells. These antigens might be useful in distinguishing precancerous from cancerous lesions. The aim of this study was to verify this assumption by comparing MAGE-A expression in benign, precancerous, and cancerous lesions of the oral mucosa. Retrospectively, biopsies of different oral lesions were randomly selected. The lesions that were included are 64 benign oral lesions (25 traumatic lesions (oral ulcers), 13 dental follicles, and 26 epulis), 26 oral lichen planus, 123 epithelial precursor lesions (32 epithelial hyperplasia found in leukoplakias, 24 epithelial dysplasia found in leukoplakias, 26 erythroplasia with oral epithelial dysplasia, and 41 carcinomas in situ in erythroleukoplakias). The lesions were immunohistochemically stained with the poly-MAGE-A antibody 57B, and the results were compared. Biopsies of oral lichen planus, oral ulcers, dental follicles, epulis, and leukoplakia without dysplasia showed no positive staining for MAGE-A antigens. Leukoplakia with dysplasia, dysplasia, and carcinomata in situ displayed positive staining in 33%, 65%, and 56% of the cases, respectively. MAGE-A antigens were not detectable via immunohistochemistry in benign lesions of the oral mucosa. The staining rate of dysplastic precancerous lesions or malignant lesions ranged from 33% to 65%. The MAGE-A antigens might facilitate better differentiation between precancerous and cancerous lesions of the oral mucosa. PMID:20174843

  4. Differences in reactive hyperemia between the intestinal mucosa and muscularis.

    PubMed

    Shepherd, A P; Riedel, G L

    1984-12-01

    In a previous study of regional intestinal blood flow by laser-Doppler velocimetry, we noted that the mucosa displayed reactive hyperemia following arterial occlusion but that the muscularis did not. Therefore, to determine whether this observation is generally valid, we compared responses of the mucosa and muscularis externa to arterial occlusion. We measured total blood flow to isolated loops of canine small bowel with an electromagnetic flow probe on the supply artery; blood flow either in the mucosa or in the muscularis was measured by laser-Doppler velocimetry. Mucosal and total blood flow consistently showed reactive hyperemia in response to a 60-s occlusion, but the muscularis did not. To determine whether metabolic rate influenced reactive hyperemia, we increased enteric oxygen uptake by placing 5% bile and transportable solutes in the lumen; these agents increased oxygen consumption by 36%. After a 60-s occlusion, the durations of both total and mucosal reactive hyperemia were significantly prolonged by increased metabolic rate. Similarly, the payback-to-debt ratios in both total and mucosal blood flows were significantly increased at elevated metabolic rate. These data support the conclusions that reactive hyperemia occurs more frequently and has a greater magnitude in the mucosa compared with the muscularis and both total and mucosal reactive hyperemia are strongly influenced by the preocclusive oxygen demand. These findings therefore constitute further evidence that metabolic factors contribute to reactive hyperemia in the intestinal circulation. PMID:6391202

  5. Campylobacter jejuni Colonization Is Associated with a Dysbiosis in the Cecal Microbiota of Mice in the Absence of Prominent Inflammation

    PubMed Central

    Lone, Abdul G.; Selinger, L. Brent; Uwiera, Richard R. E.; Xu, Yong; Inglis, G. Douglas

    2013-01-01

    Background Campylobacter jejuni causes enterocolitis in humans, but does not incite disease in asymptomatic carrier animals. To survive in the intestine, C. jejuni must successfully compete with the microbiota and overcome the host immune defense. Campylobacter jejuni colonization success varies considerably amongst individual mice, and we examined the degree to which the intestinal microbiota was affected in mice (i.e. a model carrier animal) colonized by C. jejuni at high relative to low densities. Methods Mice were inoculated with C. jejuni or buffer, and pathogen shedding and intestinal colonization were measured. Histopathologic scoring and quantification of mRNA expression for α-defensins, toll-like receptors, and cytokine genes were conducted. Mucosa-associated bacterial communities were characterized by two approaches: multiplexed barcoded pyrosequencing and terminal restriction fragment length polymorphism analysis. Results Two C. jejuni treatments were established based on the degree of cecal and colonic colonization; C. jejuni Group A animals were colonized at high cell densities, and C. jejuni Group B animals were colonized at lower cell densities. Histological examination of cecal and colonic tissues indicated that C. jejuni did not incite visible pathologic changes. Although there was no significant difference among treatments in expression of mRNA for α-defensins, toll-like receptors, or cytokine genes, a trend for increased expression of toll-like receptors and cytokine genes was observed for C. jejuni Group A. The results of the two methods to characterize bacterial communities indicated that the composition of the cecal microbiota of C. jejuni Group A mice differed significantly from C. jejuni Group B and Control mice. This difference was due to a reduction in load, diversity and richness of bacteria associated with the cecal mucosa of C. jejuni Group A mice. Conclusions High density colonization by C. jejuni is associated with a dysbiosis in

  6. Salmonella Mitigates Oxidative Stress and Thrives in the Inflamed Gut by Evading Calprotectin-Mediated Manganese Sequestration.

    PubMed

    Diaz-Ochoa, Vladimir E; Lam, Diana; Lee, Carlin S; Klaus, Suzi; Behnsen, Judith; Liu, Janet Z; Chim, Nicholas; Nuccio, Sean-Paul; Rathi, Subodh G; Mastroianni, Jennifer R; Edwards, Robert A; Jacobo, Christina M; Cerasi, Mauro; Battistoni, Andrea; Ouellette, André J; Goulding, Celia W; Chazin, Walter J; Skaar, Eric P; Raffatellu, Manuela

    2016-06-01

    Neutrophils hinder bacterial growth by a variety of antimicrobial mechanisms, including the production of reactive oxygen species and the secretion of proteins that sequester nutrients essential to microbes. A major player in this process is calprotectin, a host protein that exerts antimicrobial activity by chelating zinc and manganese. Here we show that the intestinal pathogen Salmonella enterica serovar Typhimurium uses specialized metal transporters to evade calprotectin sequestration of manganese, allowing the bacteria to outcompete commensals and thrive in the inflamed gut. The pathogen's ability to acquire manganese in turn promotes function of SodA and KatN, enzymes that use the metal as a cofactor to detoxify reactive oxygen species. This manganese-dependent SodA activity allows the bacteria to evade neutrophil killing mediated by calprotectin and reactive oxygen species. Thus, manganese acquisition enables S. Typhimurium to overcome host antimicrobial defenses and support its competitive growth in the intestine. PMID:27281571

  7. Diagnostic value of high-resolution micro-endoscopy for the classification of colon polyps

    PubMed Central

    Tan, Tao; Qu, Ya-Wei; Shu, Juan; Liu, Min-Li; Zhang, Ling; Liu, Hai-Feng

    2016-01-01

    AIM: To study a new imaging equipment, high-resolution micro-endoscopy (HRME), in the diagnosis and pathological classification of colon polyps. METHODS: We selected 114 specimens of colon polyps, 30 of which were colon polyps with known pathological types and 84 that were prospective polyp specimens; 10 normal colon mucosa specimens served as controls. We obtained images of 30 colon polyp specimens with known pathological types using HRME and analyzed the characteristics of these images to develop HRME diagnostic criteria for different pathological types of colon polyps. Based on these criteria, we performed a prospective study of 84 colon polyp specimens using HRME and compared the results with those of the pathological examination to evaluate the diagnostic value of HRME in the pathological classification of different types of colon polyps. RESULTS: In the 30 cases of known pathological type of colon polyp samples, there were 21 cases of adenomatous polyps, which comprised nine cases of tubular adenoma, seven cases of villous adenoma and five cases of mixed adenomas. The nine cases of non-adenomatous polyps included four cases of inflammatory polyps and five cases of hyperplastic polyps five. Ten cases of normal colonic mucosa were confirmed pathologically. In a prospective study of 84 cases using HRME, 23 cases were diagnosed as inflammatory polyps, 11 cases as hyperplastic polyps, 18 cases as tubular adenoma, eight cases as villous adenoma and 24 cases as mixed adenomas. After pathological examination, 24 cases were diagnosed as inflammatory polyps, 11 cases as hyperplastic polyps, 19 cases as tubular adenoma, eight cases as villous adenoma and 22 cases as mixed adenomas. Compared with the pathological examinations, the sensitivities, specificities, accuracies, and positive and negative predictive values of HRME in diagnosing inflammatory polyps (87.5%, 96.7%, 94.0%, 91.3% and 95.1%), hyperplastic polyps (72.7%, 95.9%, 92.9%, 72.7% and 95.9%), tubular adenomas

  8. Streptococcus Adherence and Colonization

    PubMed Central

    Nobbs, Angela H.; Lamont, Richard J.; Jenkinson, Howard F.

    2009-01-01

    Summary: Streptococci readily colonize mucosal tissues in the nasopharynx; the respiratory, gastrointestinal, and genitourinary tracts; and the skin. Each ecological niche presents a series of challenges to successful colonization with which streptococci have to contend. Some species exist in equilibrium with their host, neither stimulating nor submitting to immune defenses mounted against them. Most are either opportunistic or true pathogens responsible for diseases such as pharyngitis, tooth decay, necrotizing fasciitis, infective endocarditis, and meningitis. Part of the success of streptococci as colonizers is attributable to the spectrum of proteins expressed on their surfaces. Adhesins enable interactions with salivary, serum, and extracellular matrix components; host cells; and other microbes. This is the essential first step to colonization, the development of complex communities, and possible invasion of host tissues. The majority of streptococcal adhesins are anchored to the cell wall via a C-terminal LPxTz motif. Other proteins may be surface anchored through N-terminal lipid modifications, while the mechanism of cell wall associations for others remains unclear. Collectively, these surface-bound proteins provide Streptococcus species with a “coat of many colors,” enabling multiple intimate contacts and interplays between the bacterial cell and the host. In vitro and in vivo studies have demonstrated direct roles for many streptococcal adhesins as colonization or virulence factors, making them attractive targets for therapeutic and preventive strategies against streptococcal infections. There is, therefore, much focus on applying increasingly advanced molecular techniques to determine the precise structures and functions of these proteins, and their regulatory pathways, so that more targeted approaches can be developed. PMID:19721085

  9. Cadmium inhibits acid secretion in stimulated frog gastric mucosa

    SciTech Connect

    Gerbino, Andrea; Debellis, Lucantonio; Caroppo, Rosa; Curci, Silvana; Colella, Matilde

    2010-06-01

    Cadmium, a toxic environmental pollutant, affects the function of different organs such as lungs, liver and kidney. Less is known about its toxic effects on the gastric mucosa. The aim of this study was to investigate the mechanisms by which cadmium impacts on the physiology of gastric mucosa. To this end, intact amphibian mucosae were mounted in Ussing chambers and the rate of acid secretion, short circuit current (I{sub sc}), transepithelial potential (V{sub t}) and resistance (R{sub t}) were recorded in the continuous presence of cadmium. Addition of cadmium (20 {mu}M to 1 mM) on the serosal but not luminal side of the mucosae resulted in inhibition of acid secretion and increase in NPPB-sensitive, chloride-dependent short circuit current. Remarkably, cadmium exerted its effects only on histamine-stimulated tissues. Experiments with TPEN, a cell-permeant chelator for heavy metals, showed that cadmium acts from the intracellular side of the acid secreting cells. Furthermore, cadmium-induced inhibition of acid secretion and increase in I{sub sc} cannot be explained by an action on: 1) H{sub 2} histamine receptor, 2) Ca{sup 2+} signalling 3) adenylyl cyclase or 4) carbonic anhydrase. Conversely, cadmium was ineffective in the presence of the H{sup +}/K{sup +}-ATPase blocker omeprazole suggesting that the two compounds likely act on the same target. Our findings suggest that cadmium affects the functionality of histamine-stimulated gastric mucosa by inhibiting the H{sup +}/K{sup +}-ATPase from the intracellular side. These data shed new light on the toxic effect of this dangerous environmental pollutant and may result in new avenues for therapeutic intervention in acute and chronic intoxication.

  10. Endoluminal Closure of Colon Perforation with Endoscopic Band Ligation: Technical Feasibility and Safety in an In Vivo Canine Model

    PubMed Central

    Han, Joung-Ho; Kim, Myounghwan; Lee, Tae Hoon; Kim, Hyun; Jung, Yunho; Park, Seon Mee; Chae, Heebok; Youn, Seijin; Shin, Ji Yun; Lee, In-Kwang; Lee, Tae Soo; Choi, Seok Hwa

    2015-01-01

    Background/Aims: Endoscopic band ligation (EBL) is an accepted method in the management of variceal bleeding; however, there is little evidence on the safety and feasibility of EBL for the closure of bowel perforation. In this study, we aimed to evaluate the technical feasibility and efficacy of EBL in iatrogenic colon perforation by using a canine model. Methods: We established an iatrogenic colon perforation model by using seven beagle dogs. Longitudinal 1.5- to 1.7-cm colon perforations were created with a needle knife and an insulated-tip knife, and the perforation was subsequently closed with EBL. During a 2-week follow-up period, the animals were carefully monitored and then euthanized for pathologic examination. Results: The EBL of iatrogenic colon perforations was successful in all dogs. The mean procedure time for EBL closure with one to three bands was 191.7 seconds, and there were no immediate complications. One animal was euthanized after 3 days because of peritonitis. There were no clinical and laboratory features of sepsis or peritonitis in the remaining six animals. On necropsy, we did not find any fecal peritonitis, pericolonic abscess formation, or transmural dehiscence at the perforation site. Histopathology demonstrated inflamed granulation tissue and scar lesions replaced by fibrosis. Conclusions: EBL might be a feasible and safe method for the management of iatrogenic colon perforations in an in vivo model. PMID:26668801

  11. Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia

    PubMed Central

    2010-01-01

    Background The pathogenesis for colorectal cancer remains unresolved. A growing body of evidence suggests a direct correlation between cyclooxygenase enzyme expression, prostaglandin E2 metabolism and neoplastic development. Thus further understanding of the regulation of epithelial functions by prostaglandin E2 is needed. We hypothesized that patients with colonic neoplasia have altered colonic epithelial ion transport and express functionally different prostanoid receptor levels in this respect. Methods Patients referred for colonoscopy were included and grouped into patients with and without colorectal neoplasia. Patients without endoscopic findings of neoplasia served as controls. Biopsy specimens were obtained from normally appearing mucosa in the sigmoid part of colon. Biopsies were mounted in miniaturized modified Ussing air-suction chambers. Indomethacin (10 μM), various stimulators and inhibitors of prostanoid receptors and ion transport were subsequently added to the chamber solutions. Electrogenic ion transport parameters (short circuit current and slope conductance) were recorded. Tissue pathology and tissue damage before and after experiments was assessed by histology. Results Baseline short circuit current and slope conductance did not differ between the two groups. Patients with neoplasia were significantly more sensitive to indomethacin with a decrease in short circuit current of 15.1 ± 2.6 μA·cm-2 compared to controls, who showed a decrease of 10.5 ± 2.1 μA·cm-2 (p = 0.027). Stimulation or inhibition with theophylline, ouabain, bumetanide, forskolin or the EP receptor agonists prostaglandin E2, butaprost, sulprostone and prostaglandin E1 (OH) did not differ significantly between the two groups. Histology was with normal findings in both groups. Conclusions Epithelial electrogenic transport is more sensitive to indomethacin in normal colonic mucosa from patients with previous or present colorectal neoplasia compared to colonic mucosa from

  12. T Cell Receptor Sequencing Reveals the Clonal Diversity and Overlap of Colonic Effector and FOXP3+ T Cells in Ulcerative Colitis

    PubMed Central

    Lord, James; Chen, Janice; Thirlby, Richard C.; Sherwood, Anna M.; Carlson, Christopher S.

    2015-01-01

    Background & Aims FOXP3+ regulatory T cell (Tregs) prevent inflammation, but are paradoxically increased in ulcerative colitis (UC). Local T cell activation has been hypothesized to account for increased FOXP3 expression in colon lamina propria (LP) T cells. Methods To see if human FOXP3+ LP T cells are an activated fraction of otherwise FOXP3− effector T cells (Teff) and explore their clonal diversity in health and disease, we deep sequenced clonally unique T cell receptor (TCR) hypervariable regions of FOXP3+ and FOXP3− CD4+ T cell subpopulations from inflamed versus non-inflamed colon LP or mesenteric lymph nodes (MLN) of patients with or without UC. Results The clonal diversity of each LP T cell population was no different between patients with versus without UC. Repertoire overlap was only seen between a minority of FOXP3+ and FOXP3− cells, including recently activated CD38+ cells and Th17-like CD161+ Teff, but this repertoire overlap was no different between patients with versus without UC, and was no larger than the overlap between Helios− and Helios+ FOXP3+ cells. Conclusions Thus, at steady state, only a minority of FOXP3+, and particularly Helios+, T cells share a TCR sequence with FOXP3− effector populations in the colon LP, even in UC, revealing distinct clonal origins for LP Tregs and effector T cells in humans. PMID:25437819

  13. [Solitary Neurofibroma of the Sigmoid Colon Presenting as a Subepithelial Tumor Successfully Removed by Endoscopic Resection].

    PubMed

    Lee, Won Jik; Park, Sung Min; Kim, Byung Wook; Kim, Joon Sung; Ji, Jeong Seon; Choi, Hwang

    2016-07-25

    Neurofibromas are benign, slow-growing nerve sheath tumors of the peripheral nervous system, arising from Schwann cells, and classically associated with neurofibromatosis type 1 (Nf1, von Recklinghausen's disease). They occur rarely in the gastro-intestinal tract as isolated neoplasms, outside the classical clinical feature of neurofibromatosis. We herein present an isolated colonic neurofibroma without any systemic signs of neurofibromatosis. A 59-year-old female came to our hospital for constipation. On physical examination, general appearance showed no definite skin lesions. A subepithelial tumor measuring 0.8 cm was detected at the distal descending colon on colonoscopy. The lesion was removed completely by endoscopic resection. Microscopic examination showed proliferation of spindle cells in the mucosa and infiltration of inflammatory cells. Immunohistochemical staining was positive for S-100 protein. The above morphological and immunohistochemical characteristics were consistent with a diagnosis of a solitary neurofibroma of the sigmoid colon. PMID:27443624

  14. Regulatory T Cell Numbers in Inflamed Skin Are Controlled by Local Inflammatory Cues That Upregulate CD25 and Facilitate Antigen-Driven Local Proliferation.

    PubMed

    Billroth-MacLurg, Alison C; Ford, Jill; Rosenberg, Alexander; Miller, Jim; Fowell, Deborah J

    2016-09-15

    CD4(+)Foxp3(+) regulatory T cells (Tregs) are key immune suppressors that regulate immunity in diverse tissues. The tissue and/or inflammatory signals that influence the magnitude of the Treg response remain unclear. To define signals that promote Treg accumulation, we developed a simple system of skin inflammation using defined Ags and adjuvants that induce distinct cytokine milieus: OVA protein in CFA, aluminum salts (Alum), and Schistosoma mansoni eggs (Sm Egg). Polyclonal and Ag-specific Treg accumulation in the skin differed significantly between adjuvants. CFA and Alum led to robust Treg accumulation, with >50% of all skin CD4(+) T cells being Foxp3(+) In contrast, Tregs accumulated poorly in the Sm Egg-inflamed skin. Surprisingly, we found no evidence of inflammation-specific changes to the Treg gene program between adjuvant-inflamed skin types, suggesting a lack of selective recruitment or adaptation to the inflammatory milieu. Instead, Treg accumulation patterns were linked to differences in CD80/CD86 expression by APC and the regulation of CD25 expression, specifically in the inflamed skin. Inflammatory cues alone, without cognate Ag, differentially supported CD25 upregulation (CFA and Alum > Sm Egg). Only in inflammatory milieus that upregulated CD25 did the provision of Ag enhance local Treg proliferation. Reduced IL-33 in the Sm Egg-inflamed environment was shown to contribute to the failure to upregulate CD25. Thus, the magnitude of the Treg response in inflamed tissues is controlled at two interdependent levels: inflammatory signals that support the upregulation of the important Treg survival factor CD25 and Ag signals that drive local expansion. PMID:27511734

  15. Intestinal REG3 Lectins Protect against Alcoholic Steatohepatitis by Reducing Mucosa-Associated Microbiota and Preventing Bacterial Translocation.

    PubMed

    Wang, Lirui; Fouts, Derrick E; Stärkel, Peter; Hartmann, Phillipp; Chen, Peng; Llorente, Cristina; DePew, Jessica; Moncera, Kelvin; Ho, Samuel B; Brenner, David A; Hooper, Lora V; Schnabl, Bernd

    2016-02-10

    Approximately half of all deaths from liver cirrhosis, the tenth leading cause of mortality in the United States, are related to alcohol use. Chronic alcohol consumption is accompanied by intestinal dysbiosis and bacterial overgrowth, yet little is known about the factors that alter the microbial composition or their contribution to liver disease. We previously associated chronic alcohol consumption with lower intestinal levels of the antimicrobial-regenerating islet-derived (REG)-3 lectins. Here, we demonstrate that intestinal deficiency in REG3B or REG3G increases numbers of mucosa-associated bacteria and enhances bacterial translocation to the mesenteric lymph nodes and liver, promoting the progression of ethanol-induced fatty liver disease toward steatohepatitis. Overexpression of Reg3g in intestinal epithelial cells restricts bacterial colonization of mucosal surfaces, reduces bacterial translocation, and protects mice from alcohol-induced steatohepatitis. Thus, alcohol appears to impair control of the mucosa-associated microbiota, and subsequent breach of the mucosal barrier facilitates progression of alcoholic liver disease. PMID:26867181

  16. Colonic abscess induced by India ink tattooing.

    PubMed

    Bang, Chang Seok; Kim, Yeon Soo; Baik, Gwang Ho; Han, Sang Hak

    2014-07-01

    Endoscopic tattooing with India ink is generally regarded as a safe procedure that enables ready identification of endoluminal cancer from the serosal surface. However, significant complications have been reported, including local inflammatory pseudotumor formation, peritonitis, rectus muscle abscess, small bowel infarction, and phlegmonous gastritis. Although the mechanism of complication is not completely understood, it may be related to the chemical compounds contained in the ink solution and enteric or extraenteric bacterial inoculation by injection needle or the ink itself. Authors encountered a case of a 60-year-old man with a resectable sigmoid colon cancer which was tattooed with India ink for subsequent localization in the intraoperative setting. During the laparoscopic operation, the proximal and distal margin of the lesion appeared edematous with bluish color. The distal resection margin was extended approximately 5 cm more than expected because of long extent of edematous mucosa. Histologic examination of the edematous tattooing area revealed an ink abscess spreading laterally above the muscularis propria. Although tattooing is widely used and relatively safe, the presented case indicates the risk of infection or inflammation by tattooing. PMID:25073671

  17. Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome

    PubMed Central

    Lapthorne, Susan; Pereira-Fantini, Prue M.; Fouhy, Fiona; Wilson, Guineva; Thomas, Sarah L.; Dellios, Nicole L.; Scurr, Michelle; O’Sullivan, Orla; Ross, R. Paul; Stanton, Catherine; Fitzgerald, Gerald F.; Cotter, Paul D.; Bines, Julie E.

    2013-01-01

    Background and objectives Following small bowel resection (SBR), the luminal environment is altered, which contributes to clinical manifestations of short bowel syndrome (SBS) including malabsorption, mucosal inflammation and bacterial overgrowth. However, the impact of SBR on the colon has not been well-defined. The aims of this study were to characterize the colonic microbiota following SBR and to assess the impact of SBR on mucosal inflammation in the colon. Results Analysis of the colonic microbiota demonstrated that there was a significant level of dysbiosis both two and six weeks post-SBR, particularly in the phylum Firmicutes, coupled with a decrease in overall bacterial diversity in the colon. This decrease in diversity was associated with an increase in colonic inflammation six weeks post-surgery. Methods Female (4-week old) piglets (5−6/group) received a 75% SBR, a transection (sham) or no surgery. Compositional analysis of the colonic microbiota was performed by high-throughput sequencing, two- and six-weeks post-surgery. The gene expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, IL-18 and tumor necrosis factor (TNF)-α in the colonic mucosa was assessed by qRT-PCR and the number of macrophages and percentage inducible nitric oxide synthase (iNOS) staining in the colonic epithelium were quantified by immunohistochemistry. Conclusions SBR significantly decreased the diversity of the colonic microbiota and this was associated with an increase in colonic mucosal inflammation. This study supports the hypothesis that SBR has a significant impact on the colon and that this may play an important role in defining clinical outcome. PMID:23549027

  18. Human Colon-Derived Soluble Factors Modulate Gut Microbiota Composition

    PubMed Central

    Hevia, Arancha; Bernardo, David; Montalvillo, Enrique; Al-Hassi, Hafid O.; Fernández-Salazar, Luis; Garrote, Jose A.; Milani, Christian; Ventura, Marco; Arranz, Eduardo; Knight, Stella C.; Margolles, Abelardo; Sánchez, Borja

    2015-01-01

    The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting conditions and after immune – IL-15- and microbiota – LPS-in vitro challenges) were used to condition a stable fecal population. Subsequent 16S rRNA gene-based analyses were performed to study the effect induced by the host on the microbiota composition and function. Non-supervised principal component analysis (PCA) showed that all microbiotas, which had been conditioned with colonic microenvironments clustered together in terms of relative microbial composition, suggesting that soluble factors were modulating a stable fecal population independently from the treatment or the origin. Our findings confirmed that the host intestinal microenvironment has the capacity to modulate the gut microbiota composition via yet unidentified soluble factors. These findings indicate that an appropriate understanding of the factors of the host mucosal microenvironment affecting microbiota composition and function could improve therapeutic manipulation of the microbiota composition. PMID:25918688

  19. Human colon-derived soluble factors modulate gut microbiota composition.

    PubMed

    Hevia, Arancha; Bernardo, David; Montalvillo, Enrique; Al-Hassi, Hafid O; Fernández-Salazar, Luis; Garrote, Jose A; Milani, Christian; Ventura, Marco; Arranz, Eduardo; Knight, Stella C; Margolles, Abelardo; Sánchez, Borja

    2015-01-01

    The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting conditions and after immune - IL-15- and microbiota - LPS-in vitro challenges) were used to condition a stable fecal population. Subsequent 16S rRNA gene-based analyses were performed to study the effect induced by the host on the microbiota composition and function. Non-supervised principal component analysis (PCA) showed that all microbiotas, which had been conditioned with colonic microenvironments clustered together in terms of relative microbial composition, suggesting that soluble factors were modulating a stable fecal population independently from the treatment or the origin. Our findings confirmed that the host intestinal microenvironment has the capacity to modulate the gut microbiota composition via yet unidentified soluble factors. These findings indicate that an appropriate understanding of the factors of the host mucosal microenvironment affecting microbiota composition and function could improve therapeutic manipulation of the microbiota composition. PMID:25918688

  20. Bacterial colonization and gut development in preterm neonates.

    PubMed

    Cilieborg, Malene S; Boye, Mette; Sangild, Per T

    2012-03-01

    Necrotizing enterocolitis (NEC) develops in 5-10% of preterm infants in association with enteral feeding and bacterial colonization. It remains unclear how diet and bacteria interact to protect or provoke the immature gastrointestinal tract. Understanding the factors that control bacterial colonization may provide the clue to prevent NEC, and studies in infants must be combined with animal models to understand the mechanisms of the microbiota-epithelium interactions. Analyses of infant fecal samples show that the density and distribution of bacterial species are highly variable with no consistent effects of gestational age, delivery mode, diet or probiotic administration, while low bacterial diversity and bacterial overgrowth are commonly associated with NEC. A series of recent studies in preterm pigs show that the mucosa-associated microbiota is affected by delivery method, prematurity and NEC progression and that diet has limited effects. Overgrowth of specific groups (e.g. Clostridia) appears to be a consequence of NEC, rather than the cause of NEC. Administration of probiotics either decreases or increases NEC sensitivity in preterm pigs, while in preterm infants probiotics have generally decreased NEC incidence and overall mortality. The optimal nature and amount of probiotic bacteria are unknown and host defense factors appear more important for NEC sensitivity than the nature of the gut microbiota. Host defense is improved by feeding the optimal amount of enteral diets, such as mother's colostrum or milk, that help the immature intestinal immune system to respond appropriately to the highly variable bacterial colonization. PMID:22284985

  1. Sphingolipids in colon cancer

    PubMed Central

    García-Barros, Mónica; Coant, Nicolas; Truman, Jean-Philip; Snider, Ashley J.

    2013-01-01

    Colorectal cancer is one of the major causes of death in the western world. Despite increasing knowledge of the molecular signaling pathways implicated in colon cancer, therapeutic outcomes are still only moderately successful. Sphingolipids, a family of N-acyl linked lipids, have not only structural functions but are also implicated in important biological functions. Ceramide, sphingosine and sphingosine-1-phosphate are the most important bioactive lipids, and they regulate several key cellular functions. Accumulating evidence suggests that many cancers present alterations in sphingolipids and their metabolizing enzymes. The aim of this review is to discuss the emerging roles of sphingolipids, both endogenous and dietary, in colon cancer and the interaction of sphingolipids with WNT/β-catenin pathway, one of the most important signaling cascades that regulate development and homeostasis in intestine PMID:24060581

  2. Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats

    NASA Technical Reports Server (NTRS)

    Yoshida, S.; Leskiw, M. J.; Schluter, M. D.; Bush, K. T.; Nagele, R. G.; Lanza-Jacoby, S.; Stein, T. P.

    1992-01-01

    The effect of the combination of total parenteral nutrition (TPN) and systemic sepsis on mucosal morphology and protein synthesis was investigated. Rats were given a standard TPN mixture consisting of glucose (216 kcal.kg-1.day-1), lipid (24 kcal.kg-1.day-1), and amino acids (1.5 g N.kg-1.day-1) for 5 days. On the 5th day the rats (n = 37) were randomized into four groups according to diet as follows: 1) control nonseptic on standard TPN, 2) control nonseptic on TPN with glutamine, 3) septic on standard TPN, and 4) septic with the TPN supplemented with glutamine. Twenty hours after the injection of Escherichia coli, the rats were given a 4-h constant infusion of [U-14C]leucine to determine the mucosal fractional protein synthesis rates. The following results were obtained. 1) Histological examination showed that systemic sepsis caused tissue damage to the ileum and jejunum. 2) Glutamine supplementation attenuated these changes. 3) There were no visible changes to the colon either from glutamine supplementation or sepsis. 4) Sepsis was associated with an increase in mucosal protein synthesis and decreased muscle synthesis. 5) Addition of glutamine to the TPN mix further increased protein synthesis in the intestinal mucosa of septic rats.

  3. Biomechanical and histomorphometric colon remodelling in STZ-induced diabetic rats.

    PubMed

    Zhao, Jingbo; Nakaguchi, Toshiya; Gregersen, Hans

    2009-08-01

    The histomorphologic and passive biomechanical properties were studied in the mid-colon of 16 non-diabetic and 20 streptozotocin (STZ)-induced diabetic rats (50 mg/kg STZ, ip). The diabetic rats were divided into groups living 4 and 8 weeks after the induction of diabetes (n = 10 for each group). The mechanical test was a ramp distension of fluid into the colon in vitro. The colon diameter and length were obtained from digitized images of the segments at pre-selected pressures and at the no-load and zero-stress states. Circumferential and longitudinal stresses and strains were computed from the length, diameter, and pressure data and from the zero-stress state geometry. The blood glucose level increased 3-4-fold in the diabetic rats compared with the controls (P < 0.001). Diabetes generated pronounced increases in the colon weight per length, wall thickness, and wall cross-sectional area (P < 0.001). Histologically, the thickness of all layers was increased during diabetes (P < 0.05), especially the mucosa layer. The opening angle, and absolute values of residual strain increased in the diabetic group (P < 0.05 and P < 0.01, respectively). Furthermore, diabetes increased the circumferential and longitudinal stiffness of the colon wall (P < 0.001). The observed changes in residual strain, opening angle, and stress-strain relation may be contributing factors to colonic dysfunction and abdominal pain in diabetic patients. PMID:18989775

  4. Interleukin-8 stimulates the migration of human colonic epithelial cells in vitro.

    PubMed

    Wilson, A J; Byron, K; Gibson, P R

    1999-09-01

    The migration of colonic epithelial cells (restitution) is an important event in the repair of mucosal injuries. Interleukin-8 (IL-8) is a physiological initiator of the chemotactic migration of leucocytes. This study aimed to determine whether IL-8 had a similar effect on migration in an in vitro model of wounded colonic epithelium. Cell migration over 24 h was assessed in circular wounds made in confluent monolayers of the human colon cancer cell line LIM1215. This migration was stimulated in a concentration-dependent manner by IL-8, with maximal effects of approx. 1.75-fold above basal migration. The motogenic effect of IL-8 was mediated independently of effects on cell proliferation. In contrast, it was partially dependent upon gene transcription and protein synthesis and involved the activation of pertussis-toxin-sensitive G-proteins. The short-chain fatty acids, acetate, propionate, butyrate and valerate, the activator of protein kinase C (phorbol-12-myristate-13-acetate) and tumour necrosis factor-alpha (TNF-alpha) all stimulated the secretion of IL-8. However, only the motogenic effect of TNF-alpha was dependent upon IL-8. In conclusion, IL-8 stimulated cell migration in an in vitro model of colonic epithelium, whereas the motogenic effect of at least one physiologically relevant factor was dependent upon an increase in its endogenous levels. If IL-8 stimulates colonic epithelial restitution in vivo, this would have ramifications for the control of repair processes following wounding of the colonic mucosa. PMID:10464065

  5. Model based recovery of histological parameters starting from reflectance spectra of the colon

    NASA Astrophysics Data System (ADS)

    Hidovic-Rowe, Dzena; Claridge, Ela

    2005-06-01

    Colon cancer alters the tissue macro-architecture. Changes include increase in blood content and distortion of the collagen matrix, which affect the reflectance spectra of the colon and its colouration. We have developed a physics-based model for predicting colon tissue spectra. The colon structure is represented by three layers: mucosa, submucosa and smooth muscle. Each layer is represented by parameters defining its optical properties: molar concentration and absorption coefficients of haemoglobins, describing absorption of light; size and density of collagen fibres; refractive index of the medium and collagen fibres, describing light scattering; and layer thicknesses. Spectra were calculated using the Monte Carlo method. The output of the model was compared to experimental data comprising 50 spectra acquired in vivo from normal tissue. The extracted histological parameters showed good agreement with known values. An experiment was carried out to study the differences between normal and abnormal tissue. These were characterised by increased blood content and decreased collagen density, which is consistent with known differences between normal and abnormal tissue. This suggests that histological quantities of the colon could be computed from its reflectance spectra. The method is likely to have diagnostic value in the early detection of colon cancer.

  6. EFFECT OF CYLOOXYGENASE GENOTYPE AND DIETARY FISH OIL ON COLONIC EICOSANOIDS IN MICE

    PubMed Central

    Neilson, Andrew P.; Djuric, Zora; Ren, Jianwei; Hong, Yu H.; Sen, Ananda; Lager, Corey; Jiang, Yan; Reuven, Shony; Smith, William L.; Brenner, Dean E.

    2011-01-01

    Dietary ω3 fatty acids can modulate substrate availability for cyclooxygenases and lipoxygenases, thus modulating downstream eicosanoid formation. This could be an alternative approach to using NSAIDs and other COX inhibitors for limiting PGE2 synthesis in colon cancer prevention. The aims of this study were to evaluate to what extent cyclooxygenase- and lipoxygenase-derived products could be modulated by dietary fish oil in normal colonic mucosa, and to evaluate the role of COX-1 and COX-2 in formation of these products. Mice (wild-type, COX-1 null, or COX-2 null) were fed a diet supplying a broad mixture of fatty acids present in European/American diets, supplemented with either olive oil (oleate control diet) or menhaden (fish) oil ad libitum for 9–11 wk. Colonic eicosanoid levels were measured by LC-MS/MS, and proliferation was assessed by Ki67 immunohistochemistry. Dietary alteration of colonic arachidonic acid: eicosapentaenoic ratios resulted in large shifts in formation of cyclooxygenase and lipoxygenase metabolites. COX-1 knockout virtually abolished PGE2 formation but interestingly 12-HETE and 15-HETE formation was increased. The large changes in eicosanoid profiles were accompanied by relatively small changes in colonic crypt proliferation, but such changes in eicosanoid formation might have greater biological impact upon carcinogen challenge. These results indicate that in normal colon, inhibition of COX-2 would have little effect on reducing PGE2 levels. PMID:21937210

  7. Urocortins and CRF receptor type 2 variants in the male rat colon: gene expression and regulation by endotoxin and anti-inflammatory effect.

    PubMed

    Yuan, Pu-Qing; Wu, S Vincent; Pothoulakis, Charalabos; Taché, Yvette

    2016-03-15

    Urocortins (Ucns) 1, 2, and 3 and corticotropin-releasing factor receptor 2 (CRF2) mRNA are prominently expressed in various layers of the upper gut. We tested whether Ucns and CRF2 variants are also expressed in the different layers of the rat colon, regulated by LPS (100 μg/kg ip) and play a modulatory role in the colonic immune response to LPS. Transcripts of Ucns and CRF2b, the most common isoform in the periphery, were detected in all laser microdissected layers, including myenteric neurons. LPS increased the mRNA level of Ucn 1, Ucn 2, and Ucn 3 and decreased that of CRF2b in both the colonic mucosa and submucosa + muscle (S+M) layers at 2, 6, and 9 h after injection with a return to basal at 24 h. In addition, CRF2a, another variant more prominent in the brain, and a novel truncated splice variant CRF2a-3 mRNA were detected in all segments of the large intestine. LPS reciprocally regulated the colonic expression of these CRF2 variants by decreasing both CRF2a and CRF2b, while increasing CRF2a-3 in the mucosa and S+M. The CRF2 antagonist astressin2-B further enhanced LPS-induced increase of mRNA level of interleukin (IL)-1β, TNF-α, and inducible nitric oxide synthase in S+M layers and IL-1β in the mucosa and evoked TNF-α expression in the mucosa. These data indicate that Ucns/CRF2 variants are widely expressed in all colonic layers and reciprocally regulated by LPS. CRF2 signaling dampens the CD14/TLR4-mediated acute inflammatory response to Gram-negative bacteria in the colon. PMID:26744472

  8. Olfactory Mucosa Tissue Based Biosensor for Bioelectronic Nose

    NASA Astrophysics Data System (ADS)

    Liu, Qingjun; Ye, Weiwei; Yu, Hui; Hu, Ning; Cai, Hua; Wang, Ping

    2009-05-01

    Biological olfactory system can distinguish thousands of odors. In order to realize the biomimetic design of electronic nose on the principle of mammalian olfactory system, we have reported bioelectronic nose based on cultured olfactory cells. In this study, the electrical property of the tissue-semiconductor interface was analyzed by the volume conductor theory and the sheet conductor model. Olfactory mucosa tissue of rat was isolated and fixed on the surface of the light-addressable potentiometric sensor (LAPS), with the natural stations of the neuronal populations and functional receptor unit of the cilia well reserved. By the extracellular potentials of the olfactory receptor cells of the mucosa tissue monitored, both the simulation and the experimental results suggested that this tissue-semiconductor hybrid system was sensitive to odorants stimulation.

  9. [Microflora of pharyngeal mucosa in children with solid tumors].

    PubMed

    Polishchuk, V B; Baturo, A P; Romanenko, E E; Kostinov, M P; Zaeva, G E; Mikhaĭlova, S N; Leonova, A Iu; Moiseenko, E I

    2008-01-01

    Microbiological study of pharyngeal mucosa in 43 children with solid tumors revealed that 77.2% of isolated microorganisms belonged to Gram-positive flora. It was shown that streptococci and Staphylococcus aureus were the main species. Species composition of streptococci included both pyogenic (S. pyogenes, S. agalactiae, S. dysgalactiae, S. equi) andviridans species (S. acidominimus, S. oralis and "S. milleri" group). Nocardioform actinomycetes, corynebacteria and other staphylococci were referred to additional microflora. Accidental microflora was represented by Neisseria spp., non-fermenting Gram-negative bacteria, enterobacteria and yeast-like fungi. Microbiologic study of pharyngeal mucosa biocenosis showed that monoculture was present only in 2.3% of cases; in other cases microorganisms formed both intra-genus and inter-species associations. 2-6-component associations were revealed with predominance of 3-4-component associations (37.2% and 32.6% respectively). Relationship of distribution of microorganisms belonging to main and additional microflora was revealed. PMID:19186552

  10. Concentrations of acidic antiinflammatory drugs in gastric mucosa.

    PubMed

    Frey, H H; El-Sayed, M A

    1977-12-01

    In rats, the concentrations of the acidic antiinflammatory drugs salicylic acid, acetylsalicylic acid, phenylbutazone, flufenamic acid and indomethacin in the glandular portion of the gastric mucosa were determined 30 and 60 min after oral or subcutaneous administration. In another series of experiments, solutions of the drugs were introduced into the ligated stomach and the concentrations in the mucosa and in the contents of the stomach were determined after 60 min. The ratio between the concentrations in the musoca and those in serum or gastric contents were much lower than expected according to the distribution by passive non-ionic diffusion. This apparent discrepancy may be explained as a result of a drug-induced damage to the mucosal cell allowing free diffusion of ionized drug across the cell membrane. PMID:603322

  11. Two Cases of Bacteremia Due to Roseomonas mucosa

    PubMed Central

    Kim, Yu Kyung; Moon, Jung Suk; Song, Kyung Eun

    2016-01-01

    Roseomonas is a genus of pink-pigmented nonfermentative bacilli. These slow-growing, gram-negative cocobacilli form pink-colored colonies on sheep blood agar. They differ from other pink-pigmented nonfermenters, including Methylobacterium, in morphology, biochemical characteristics, and DNA sequence. Roseomonas strains are rarely isolated in clinical laboratories; therefore, we report two cases in order to improve our ability to identify these pathogens. We isolated two strains of Roseomonas mucosa from the venous blood cultures of two patients, an 84-yr-old woman with common bile duct obstruction and a 17-yr-old male with acute myeloid leukemia who had an indwelling central-venous catheter for chemotherapy. The isolated strains were confirmed as R. mucosa by 16S rRNA sequencing. PMID:27139611

  12. Reduced expression of aquaporins in human intestinal mucosa in early stage inflammatory bowel disease

    PubMed Central

    Ricanek, Petr; Lunde, Lisa K; Frye, Stephan A; Støen, Mari; Nygård, Ståle; Morth, Jens P; Rydning, Andreas; Vatn, Morten H; Amiry-Moghaddam, Mahmood; Tønjum, Tone

    2015-01-01

    Objectives The aim of this study was to investigate the relationship between aquaporin (AQP) water channel expression and the pathological features of early untreated inflammatory bowel disease (IBD) in humans. Methods Patients suspected to have IBD on the basis of predefined symptoms, including abdominal pain, diarrhea, and/or blood in stool for more than 10 days, were examined at the local hospital. Colonoscopy with biopsies was performed and blood samples were taken. Patients who did not meet the diagnostic criteria for IBD and who displayed no evidence of infection or other pathology in the gut were included as symptomatic non-IBD controls. AQP1, 3, 4, 5, 7, 8, and 9 messenger RNA (mRNA) levels were quantified in biopsies from the distal ileum and colon by quantitative real-time polymerase chain reaction. Protein expression of selected AQPs was assessed by confocal microscopy. Through multiple alignments of the deduced amino acid sequences, the putative three-dimensional structures of AQP1, 3, 7, and 8 were modeled. Results AQP1, 3, 7, and 8 mRNAs were detected in all parts of the intestinal mucosa. Notably, AQP1 and AQP3 mRNA levels were reduced in the ileum of patients with Crohn’s disease, and AQP7 and AQP8 mRNA levels were reduced in the ileum and the colon of patients with ulcerative colitis. Immunofluorescence confocal microscopy showed localization of AQP3, 7, and 8 at the mucosal epithelium, whereas the expression of AQP1 was mainly confined to the endothelial cells and erythrocytes. The reduction in the level of AQP3, 7, and 8 mRNA was confirmed by immunofluorescence, which also indicated a reduction of apical immunolabeling for AQP8 in the colonic surface epithelium and crypts of the IBD samples. This could indicate loss of epithelial polarity in IBD, leading to disrupted barrier function. Conclusion AQPs 1 and 8 and the aquaglyceroporins AQPs 3 and 7 are the AQPs predominantly expressed in the lower intestinal tract of humans. Their expression is

  13. The quantitative assessment of normal canine small intestinal mucosa.

    PubMed

    Hart, I R; Kidder, D E

    1978-09-01

    Quanitative methods of assessing the architecture of small intestinal mucosa have been applied to biopsy material from normal dogs. Mucosal samples taken from four predetermined sites show that there are significant quantitative differences between the various levels of the small bowel. Animals of one year of age and older show no correlation between age or weight and mucosal dimensions. The significance of these findings, in relation to examination of biopsy material from cases of clinical small intestinal disease, is discussed. PMID:364574

  14. Zur Struktur der Solenocyten (Cyrtocyten) von Anaitides mucosa (Annelida, Polychaeta)

    NASA Astrophysics Data System (ADS)

    Hausmann, K.

    1981-12-01

    Based on electron microscopic observations, the structure of the solenocytes of A. mucosa is described. The tube of the solenocyte is made up of 14 15 rods. These rods, which are filled with regularly packed filaments, are interconnected by an amorphous to filamentous substance. A single flagellum, lying in the tube, is surrounded by a sheet of amorphous material. The functional organization of the solenocytes is discussed.

  15. Distant Skin Metastases from Carcinoma Buccal Mucosa: A Rare Presentation

    PubMed Central

    Srinivasan, Shashank; Leekha, Nitin; Gupta, Sweety; Mithal, Umang; Arora, Vandana; De, Sudarsan

    2016-01-01

    Cancer of the oral cavity makes up approximately 30% of all head and neck region tumors. Skin metastasis is rare with an incidence ranging between 0.7% and 2.4%. Skin metastasis usually occurs in the neck, scalp, and over the skin near the primary site. We report a patient with carcinoma left buccal mucosa who presented with distant skin metastases to the right side chest wall. PMID:27512210

  16. Zollinger-Ellison syndrome with esophagitis and Barrett mucosa.

    PubMed

    Karl, T R; Pindyck, F; Sicular, A

    1983-10-01

    Although esophageal disease in Zollinger-Ellison syndrome is being recognized with increasing frequency, Barrett esophagus is seen only rarely. Basal lower esophageal sphincter pressure is probably not different in Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome patients. Circulating gastrin, therefore, cannot be the major determinant of lower esophageal sphincter pressure in vivo. Total gastrectomy and resection of all metaplastic esophagus, when feasible, is the treatment of choice for patients with Zollinger-Ellison syndrome and Barrett mucosa. PMID:6624733

  17. Untersuchungen zur Regeneration des Hinterendes bei Anaitides mucosa (Polychaeta, Phyllodocidae)

    NASA Astrophysics Data System (ADS)

    Röhrkasten, A.

    1983-06-01

    Caudal regeneration was investigated in decerebrate Anaitides mucosa and in brain-intact individuals. Both groups show an identical capacity to regenerate lost caudal segments. Furthermore there is no difference in males and females. Low temperature (5 °C) inhibits the regeneration of caudal segments, but it is necessary for normal oogenesis. Under conditions of high temperature (15 °C), caudal regeneration is very extensive. At the same time degeneration of most oocytes occurs.

  18. Distant Skin Metastases from Carcinoma Buccal Mucosa: A Rare Presentation.

    PubMed

    Srinivasan, Shashank; Leekha, Nitin; Gupta, Sweety; Mithal, Umang; Arora, Vandana; De, Sudarsan

    2016-01-01

    Cancer of the oral cavity makes up approximately 30% of all head and neck region tumors. Skin metastasis is rare with an incidence ranging between 0.7% and 2.4%. Skin metastasis usually occurs in the neck, scalp, and over the skin near the primary site. We report a patient with carcinoma left buccal mucosa who presented with distant skin metastases to the right side chest wall. PMID:27512210

  19. Evaluation of Microbial Load in Oropharyngeal Mucosa from Tannery Workers

    PubMed Central

    Castellanos-Arévalo, Diana C.; Castellanos-Arévalo, Andrea P.; Camarena-Pozos, David A.; Colli-Mull, Juan G.; Maldonado-Vega, María

    2014-01-01

    Background Animal skin provides an ideal medium for the propagation of microorganisms and it is used like raw material in the tannery and footware industry. The aim of this study was to evaluate and identify the microbial load in oropharyngeal mucosa of tannery employees. Methods The health risk was estimated based on the identification of microorganisms found in the oropharyngeal mucosa samples. The study was conducted in a tanners group and a control group. Samples were taken from oropharyngeal mucosa and inoculated on plates with selective medium. In the samples, bacteria were identified by 16S ribosomal DNA analysis and the yeasts through a presumptive method. In addition, the sensitivity of these microorganisms to antibiotics/antifungals was evaluated. Results The identified bacteria belonged to the families Enterobacteriaceae, Pseudomonadaceae, Neisseriaceae, Alcaligenaceae, Moraxellaceae, and Xanthomonadaceae, of which some species are considered as pathogenic or opportunistic microorganisms; these bacteria were not present in the control group. Forty-two percent of bacteria identified in the tanners group are correlated with respiratory diseases. Yeasts were also identified, including the following species: Candida glabrata, Candida tropicalis, Candida albicans, and Candida krusei. Regarding the sensitivity test of bacteria identified in the tanners group, 90% showed sensitivity to piperacillin/tazobactam, 87% showed sensitivity to ticarcillin/clavulanic acid, 74% showed sensitivity to ampicillin/sulbactam, and 58% showed sensitivity to amoxicillin/clavulanic acid. Conclusion Several of the bacteria and yeast identified in the oropharyngeal mucosa of tanners have been correlated with infections in humans and have already been reported as airborne microorganisms in this working environment, representing a health risk for workers. PMID:25830072

  20. l-Menthol sprayed on gastric mucosa causes edematous change

    PubMed Central

    Mori, Akihiro; Hachiya, Hiroki; Yumura, Takayuki; Ito, Shun; Hayashi, Shintaro; Nozaki, Masashi; Yoshida, Atsui; Ohashi, Noritsugu

    2014-01-01

    Background and study aims: l-Menthol (LM), sprayed on the distal gastric mucosa, is a safe antispasmodic agent used during esophagogastroduodenoscopy (EGD). However, it seems to affect gastric mucosal endoscopic findings. Therefore, we evaluated whether LM causes specific changes and impacts the endoscopic morphology of gastric lesions. Patients and methods: A total of 98 patients scheduled to undergo EGD were randomly assigned to receive LM solution (160 mg of 0.8 % LM added to 2.5 mL of indigo carmine [IC]; n = 49; LM group) or decuple-diluted IC solution without LM (n = 49; placebo group). We compared the incidence of specific mucosal changes and the difference in the endoscopic findings of several gastric lesions between these groups. Results: Annular-reticular – like mucosal changes appeared immediately after the administration of LM solution. This change was observed in 71.4 % of the LM group compared with 12.2 % of the placebo group (P < 0.01). In the placebo group, this change was observed in 14.7 % of subjects with atrophic gastritis compared with 6.7 % of those without atrophic gastritis (P = 0.39), whereas in the LM group, this change was observed in 84.8 % of subjects with atrophic gastritis compared with 43.8 % of those without atrophic gastritis (P < 0.01). Most early gastric cancers, erosions, and ulcers observed in this study became well demarcated after LM administration, although the incidence of gastric lesions did not differ significantly between the two groups. Conclusion: LM changes the gastric mucosa into edematous mucosa, and this occurs more frequently in atrophic gastric mucosa than in pathologic lesions. LM may facilitate the demarcation of pathologic gastric lesions without intestinal metaplasia. PMID:26135260

  1. Method of expression of certain bacterial microflora mucosa olfactory area

    NASA Astrophysics Data System (ADS)

    Avrunin, Oleg G.; Nosova, Yana V.; Shushlyapina, Natalia O.; Surtel, Wojciech; Burlibay, Aron; Zhassandykyzy, Maral

    2015-12-01

    The article is devoted to the actual problem - the development of new express diagnostic methods, based on which a doctor-otolaryngologist can quickly and efficiently determine a violation of smell. The work is based on the methods of processing and analysis of medical images and signals. We have also identified informative indicators of endoscopic image of the olfactory region of the nasal mucosa of the upper course.

  2. Routine colonic endoscopic evaluation following resolution of acute diverticulitis: is it necessary?

    PubMed

    Agarwal, Amit K; Karanjawala, Burzeen E; Maykel, Justin A; Johnson, Eric K; Steele, Scott R

    2014-09-21

    Diverticular disease incidence is increasing up to 65% by age 85 in industrialized nations, low fiber diets, and in younger and obese patients. Twenty-five percent of patients with diverticulosis will develop acute diverticulitis. This imposes a significant burden on healthcare systems, resulting in greater than 300000 admissions per year with an estimated annual cost of $3 billion USD. Abdominal computed tomography (CT) is the diagnostic study of choice, with a sensitivity and specificity greater than 95%. Unfortunately, similar CT findings can be present in colonic neoplasia, especially when perforated or inflamed. This prompted professional societies such as the American Society of Colon Rectal Surgeons to recommend patients undergo routine colonoscopy after an episode of acute diverticulitis to rule out malignancy. Yet, the data supporting routine colonoscopy after acute diverticulitis is sparse and based small cohort studies utilizing outdated technology. While any patient with an indication for a colonoscopy should undergo appropriate endoscopic evaluation, in the era of widespread use of high-resolution computed tomography, routine colonic endoscopic evaluation following resolution of acute uncomplicated diverticulitis poses additional costs, comes with inherent risks, and may require further study. In this manuscript, we review the current data related to this recommendation. PMID:25253951

  3. Diffuse lymphoid follicles of the colon associated with colonic carcinoma.

    PubMed

    Bronen, R A; Glick, S N; Teplick, S K

    1984-01-01

    In four patients aged 59-75 years, colonic carcinoma was associated with diffuse lymphoid follicles in the colon. In one case, the prominence and distribution of the lymphoid follicles corresponded to the progression and regression of the tumor bulk. It is extremely unusual to demonstrate lymphoid follicles, particularly diffuse, on barium enema in patients in this age range. The colonic carcinomas and lymphoid follicles are directly related, possibly representing an immune response. PMID:6606941

  4. Neuroendocrine changes in colon of mice with a disrupted IL-2 gene.

    PubMed

    Qian, B F; El-Salhy, M; Melgar, S; Hammarström, M L; Danielsson, A

    2000-06-01

    in normal colon. On the other hand, there were some changes that seemed to correlate with the bowel inflammatory process. They might be associated with the impaired function in inflamed gut and contribute to the development and/or prolongation of disease. PMID:10844519

  5. Incidence of bone metastasis in carcinoma buccal mucosa

    PubMed Central

    Bhandari, Virendra

    2016-01-01

    Introduction: Head and neck cancer is a leading health problem in India due to the habit of chewing tobacco and bad oral and dental hygiene. Carcinoma buccal mucosa is more common and is 2.5% of all malignancies at our center. Most of the patients present in stage III and IV and the survival in these cases is not very good. Bone metastasis in advanced cases of carcinoma buccal mucosa is rarely reported in the world literature. Materials and Methods: We present here cases developing bone metastasis in carcinoma buccal mucosa in last 5 years. These patients were young with loco-regionally advanced disease where bone metastasis developed within 1-year of definitive treatment. Results: The flat bones and vertebrae were mainly involved and the survival was also short after diagnosis of metastasis despite the treatment with local Radiotherapy and chemotherapy. Conclusion: The exact cause of metastasis cannot be proved, but the probability of subclinical seedling of malignant cells before the eradication of the primary tumor should be considered along with advanced local and nodal disease with high grade of tumor. PMID:27168702

  6. Local Immunoglobulin E in the Nasal Mucosa: Clinical Implications

    PubMed Central

    De Schryver, Els; Devuyst, Lien; Derycke, Lara; Dullaers, Melissa; Van Zele, Thibaut; Bachert, Claus

    2015-01-01

    Immunoglobulin E (IgE) can be highly elevated in the airway mucosa independently of IgE serum levels and atopic status. Mostly, systemic markers are assessed to investigate inflammation in airway disease for research or clinical practice. A more accurate but more cumbersome approach to determine inflammation at the target organ would be to evaluate markers locally. We review evidence for local production of IgE in allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP). Diagnostic and therapeutic consequences in clinical practice are discussed. We describe that the airway mucosa has the intrinsic capability to produce IgE. Moreover, not only do IgE-positive B cells reside within the mucosa, but all tools are present locally for affinity maturation by somatic hypermutation (SHM), clonal expansion, and class switch recombination to IgE. Recognizing local IgE in the absence of systemic IgE has diagnostic and therapeutic consequences. Therefore, we emphasize the importance of local IgE in patients with a history of AR or CRSwNP. PMID:25749769

  7. Nested PCR for detection of HSV-1 in oral mucosa

    PubMed Central

    Jalouli, Miranda-Masoumeh; Jalouli, Jamshid; Hasséus, Bengt; Öhman, Jenny; Hirsch, Jan-Michaél

    2015-01-01

    Background It has been estimated that 15%-20% of human tumours are driven by infection and inflammation, and viral infections play an important role in malignant transformation. The evidence that herpes simplex virus type 1 (HSV-1) could be involved in the aetiology of oral cancer varies from weak to persuasive. This study aimed to investigate by nested PCR (NPCR) the prevalence of HSV-1 in samples from normal oral mucosa, oral leukoplakia, and oral squamous cell carcinoma (OSCC). Material and Methods We investigated the prevalence of HSV-1 in biopsies obtained from 26 fresh, normal oral mucosa from healthy volunteers as well as 53 oral leukoplakia and 27 OSCC paraffin-embedded samples. DNA was extracted from the specimens and investigated for the presence of HSV-1 by nested polymerase chain reaction (NPCR) and DNA sequencing. Results HSV-1 was detected in 14 (54%) of the healthy samples, in 19 (36%) of the oral leukoplakia samples, and in 14 (52%) of the OSCC samples. The differences were not statistically significant. Conclusions We observed a high incidence of HSV-1 in healthy oral mucosa, oral leukoplakia, and OSCC tissues. Thus, no connection between OSCC development and presence of HSV-1 was detected. Key words:HSV-1, nested PCR, PCR. PMID:26449432

  8. Acylation of lysolecithin in the intestinal mucosa of rats

    PubMed Central

    Subbaiah, P. V.; Sastry, P. S.; Ganguly, J.

    1970-01-01

    1. The presence of an active acyl-CoA–lysolecithin (1-acylglycerophosphorylcholine) acyltransferase was demonstrated in rat intestinal mucosa. 2. ATP and CoA were necessary for the incorporation of free [1-14C]oleic acid into lecithin (phosphatidylcholine). 3. The reaction was about 20 times as fast with [1-14C]oleoyl-CoA as with free oleic acid, CoA and ATP. 4. With 1-acylglycerophosphorylcholine as the acceptor, both oleic acid and palmitic acid were incorporated into the β-position of lecithin; the incorporation of palmitic acid was 60% of that of oleic acid. 5. Of the various analogues of lysolecithin tested as acyl acceptors from [1-14C]oleoyl CoA, a lysolecithin with a long-chain fatty acid at the 1-position was most efficient. 6. The enzyme was mostly present in the brush-border-free particulate fraction of the intestinal mucosa. 7. Of the various tissues of rats tested for the activity, intestinal mucosa was found to be the most active, with testes, liver, kidneys and spleen following it in decreasing order. PMID:5484668

  9. Proteomic analysis of minute amount of colonic biopsies by enteroscopy sampling.

    PubMed

    Liu, Xing; Xu, Yanli; Meng, Qian; Zheng, Qingqing; Wu, Jianhong; Wang, Chen; Jia, Weiping; Figeys, Daniel; Chang, Ying; Zhou, Hu

    2016-08-01

    Colorectal cancer (CRC) is one of the most common types of malignant tumor worldwide. Currently, although many researchers have been devoting themselves in CRC studies, the process of locating biomarkers for CRC early diagnosis and prognostic is still very slow. Using a centrifugal proteomic reactor-based proteomic analysis of minute amount of colonic biopsies by enteroscopy sampling, 2620 protein groups were quantified between cancer mucosa and adjacent normal colorectal mucosa. Of which, 403 protein groups were differentially expressed with statistic significance between cancer and normal tissues, including 195 up-regulated and 208 down-regulated proteins in cancer tissues. Three proteins (SOD3, PRELP and NGAL) were selected for further Western blot validation. And the resulting Western blot experimental results were consistent with the quantitative proteomic data. SOD3 and PRELP are down-regulated in CRC mucosa comparing to adjacent normal tissue, while NGAL is up-regulated in CRC mucosa. In conclusion, the centrifugal proteomic reactor-based label-free quantitative proteomic approach provides a highly sensitive and powerful tool for analyzing minute protein sample from tiny colorectal biopsies, which may facilitate CRC biomarkers discovery for diagnoses and prognoses. PMID:27230957

  10. Gadolinium chloride improves the course of TNBS and DSS-induced colitis through protecting against colonic mucosal inflammation

    PubMed Central

    Du, Chao; Wang, Peng; Yu, Yanbo; Chen, Feixue; Liu, Jun; Li, Yanqing

    2014-01-01

    Inflammatory macrophages in colonic mucosa are the leading drivers of the pathology associated with inflammatory bowel disease (IBD). Here we examined whether gadolinium chloride (GdCl3), a macrophage selective inhibitor, would improve the course of 2,4,6-trinitro benzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS)-induced colitis in mice and the potential mechanisms were investigated. By giving GdCl3 to colitis mice through intravenous or intrarectal route, we found that GdCl3 markedly ameliorated the colitis severity, including less weight loss, decreased disease activity index scores, and improved mucosal damage. To investigate the potential mechanisms, flow-cytometric analysis was performed to detect the proportion of mucosal macrophages in colon. The results showed that GdCl3 had no macrophage depletion effect in colonic mucosa, but significantly suppressed TNBS and DSS-induced TNFα, IL-1β and IL-6 secretions. Also, Western blotting analysis indicated that NF-κB p65 expression was significantly attenuated in the mucosa in colitis mice with GdCl3 treatment. Then, the anti-inflammatory activity of GdCl3 was confirmed in LPS-stimulated RAW 264.7 cells that GdCl3 might down-regulate the production of proinflammatory cytokines by macrophages through inhibition of the NF-κB signaling pathway. Therefore, intervention with mucosal inflammatory macrophages may be a promising therapeutic target in IBD. PMID:25146101

  11. Effects of cigarette smoke and ethanol intake on mouse oesophageal mucosa changes induced by dietary zinc deficiency and deoxycholic acid supplementation.

    PubMed

    Zapaterini, Joyce R; de Moura, Nelci A; Ribeiro, Daniel A; Rodrigues, Maria A M; Barbisan, Luis F

    2012-08-01

    The noxious effects of dietary zinc deficiency (ZD) and deoxycholic bile acid (DCA) supplementation in the oesophagus were investigated. The additional influence of cigarette smoke and ethanol intake on the changes in the oesophageal mucosa induced by dietary ZD plus DCA was also assessed. Male C57BL/6 mice were allocated into four groups: Group 1 was fed control diet and groups 2-4 were fed ZD plus DCA diet. After 5 weeks, groups 3 and 4 were exposed to 10% ethanol intake or cigarette smoke for 15 weeks, respectively. All animals were euthanized at the end of week 20, and the oesophagus, lung, liver and colon were collected and analysed by conventional morphology. Cell proliferation was assessed in the oesophageal mucosa by Ki-67 immunohistochemistry and cyclooxygenase 2 (COX-2) protein by Western blotting. Dietary ZD plus DCA treatment induced mild hyperkeratosis and hyperplasia, increased cell proliferation index and COX-2 protein expression in the oesophagus, and intranuclear inclusion, karyocytomegaly and microvesicular fatty change in the liver. Cigarette smoke increased COX-2 protein expression in oesophageal mucosa and irregular enlargement of alveolus and alveolar ductal air spaces, while ethanol enhanced liver damage induced by ZD plus DCA diet. These findings indicate that dietary ZD plus DCA treatment during 20 weeks induces a pattern of chemical oesophageal injury but not Barrett's-like lesions. PMID:22380924

  12. Prelamination of Neourethra with Uterine Mucosa in Radial Forearm Osteocutaneous Free Flap Phalloplasty in the Female-to-Male Transgender Patient

    PubMed Central

    Salgado, Christopher J.; Chim, Jimmy; Medina, Carlos A.; Demaso, Stephanie; Gomez, Christopher

    2016-01-01

    Radial forearm free flap phalloplasty is the most commonly performed flap for neophallus construction in the female-to-male (FtM) transgender patient. Urological complications, however, can arise quite frequently and can prevent the patient from urinating in the standing position, an important postsurgical goal for many. Using mucosa to construct the fixed urethra and to prelaminate the penile urethra has been successful in reducing urologic complications, particularly strictures and fistulas. Until now, only buccal, vaginal, colonic, and bladder sites have been described as sources for these mucosal grafts. We present the successful use of uterine mucosa for prelamination of the neourethra in an FtM patient who underwent hysterectomy and vaginectomy at the prelamination stage of a radial forearm phalloplasty. Three months postoperatively, the patient was able to void while standing and showed no evidence of stricture or fistula on retrograde cystogram. These results suggest that uterine mucosa may be used for prelamination of the penile neourethra in patients undergoing phalloplasty. PMID:27069708

  13. Expression of H type 1 antigen of ABO histo-blood group in normal colon and aberrant expressions of H type 2 and H type 3/4 antigens in colon cancer.

    PubMed

    Fujitani, N; Liu, Y; Toda, S; Shirouzu, K; Okamura, T; Kimura, H

    2000-05-01

    We have immunohistochemically examined the distribution of the H antigens of type 1, type 2 and type 3/4 chains of the ABO(H) histo-blood group system in human normal colon and in colon cancer using three monoclonal antibodies specific for each of the H type 1/2, H type 2, and the H type 3/4 chain. We unexpectedly found that mucosa of the normal colon from secretors but not that from nonsecretors expressed only H type 1 and did not express H type 2 or H type 3/4. The H type 1 was expressed in goblet cells. Positive goblet cells expressing H type 1 were decreased in number progressively from the proximal colon to the rectum. In tumors, 4 (57%) of 7 cancer tissues of the proximal colon from secretors expressed no H type 1, whereas all 8 cancer tissues of the distal colon from secretors expressed H type 1. The aberrant expressions of H type 2 and H type 3/4 (47 and 67%, respectively) were found in cancer tissues from both the proximal and the distal colon. Tumors from nonsecretors did not express any H antigens. Our results suggested that the expression of H type 1 in the normal colon and the aberrant expressions of H type 2 and H type 3/4 in colon cancer tissues were regulated by FUT2-encoded Se type alpha(1,2)fucosyltransferase. However, UEA-I-positive substance(s) rather than H type 2 were uniquely expressed throughout the normal colon and in colon cancers from both secretors and nonsecretors. PMID:11261842

  14. Functional and molecular evidence for β1-, β2- and β3-adrenoceptors in human colon

    PubMed Central

    Roberts, S J; Papaioannou, M; Evans, B A; Summers, R J

    1997-01-01

    Relaxation of carbachol pre-contracted human colonic muscle to (–)-isoprenaline was examined in circular, longitudinal and taenia coli preparations to determine the β-adrenoceptor subtypes involved. β1-, β2- and β3-Adrenoceptor mRNAs were also measured in colonic muscle and mucosa.(–)-Isoprenaline caused relaxation of longitudinal smooth muscle preparations with pEC50=7.39±0.12, and this response was inhibited by both propranolol (0.1 μM, pKB 8.55±0.12) and the selective β1-antagonist, CGP 20712A (0.1 μM, pKB 8.80±0.20), while the selective β2-antagonist, ICI 118551 (0.1 μM) failed to inhibit isoprenaline relaxation consistently.(–)-Isoprenaline caused relaxation of taenia coli with a pEC50 of 6.70±0.17. Propranolol (0.1 μM), CGP 20712A (0.1 μM) and ICI 118551 (0.1 μM) inhibited the isoprenaline response with similar low affinities (pKB values 7.93, 7.71 and 7.54, respectively). Carbachol pre-contracted circular smooth muscle preparations failed to relax consistently to isoprenaline and these responses were not characterized.β1- and β2-Adrenoceptor mRNAs were present in circular/longitudinal muscle samples and taenia coli samples, and lower levels were detected in mucosa. β3-mRNA was also present in both muscle preparations but was not detected in human colonic mucosa.In summary, β1-adrenoceptors are the predominant subtype mediating isoprenaline-induced relaxation of the thin longitudinal smooth muscle of human colon, while β3-receptors do not appear to be involved in these responses. However, β3-adrenoceptors may play a role in relaxation of the taenia coli as conventional antagonist affinities are low. β3-Adrenoceptor mRNA was present in taenia coli and circular/longitudinal smooth muscle but absent from human colonic mucosa. PMID:9113375

  15. Outcome of buccal mucosa and lingual mucosa graft urethroplasty in the management of urethral strictures: A comparative study

    PubMed Central

    Chauhan, Sharad; Yadav, Sher Singh; Tomar, Vinay

    2016-01-01

    Objective: The objective of the study was to compare the outcome of buccal and lingual mucosa graft (LMG) augmentation urethroplasty along with donor sites morbidities in anterior urethra stricture. Subjects and Methods: From September 2010 to January 2014, 125 patients underwent single stage augmentation urethroplasty. They were randomly divided into two groups to receive either buccal mucosa graft (BMG) or LMG. The patients were prospectively followed for complications and outcome. Results: Baseline characteristics such as mean age, etiology, stricture length, and location were comparable in both groups. Overall success rate for Group 1 and Group 2 were 69.2% and 80%, respectively. Mean follow-up periods were 28.2 and 25 months in Group 1 and Group 2, respectively. Conclusions: LMG provides the better outcome with fewer immediate and delayed complications as compared to BMG. The length of stricture and width of graft were main factors affecting the outcome. PMID:26834399

  16. Colon-targeted delivery of budesonide using dual pH- and time-dependent polymeric nanoparticles for colitis therapy

    PubMed Central

    Naeem, Muhammad; Choi, Moonjeong; Cao, Jiafu; Lee, Yujeong; Ikram, Muhammad; Yoon, Sik; Lee, Jaewon; Moon, Hyung Ryong; Kim, Min-Soo; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Single pH-dependent drug delivery systems have been widely used for colon-targeted delivery, but their efficiency is often hampered by the variation in gut pH. To overcome the limitation of single pH-dependent delivery systems, in this study, we developed and evaluated the therapeutic potential of budesonide-loaded dual pH/time-dependent nanoparticles (NPs) for the treatment of colitis. Eudragit FS30D was used as a pH-dependent polymer, and Eudragit RS100 as a time-dependent controlled release polymer. Single pH-dependent NPs (pH_NPs), single time-dependent NPs (Time_NPs), and dual pH/time-dependent NPs (pH/Time_NPs) were prepared using the oil-in-water emulsion method. The physicochemical properties and drug release profiles of these NPs in gastrointestinal (GI) tract conditions were investigated. The therapeutic potential and in vivo distribution of the NPs were evaluated in a dextran sulfate sodium (DSS)-induced colitis mice model. The pH/Time_NPs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. The in vivo distribution study in the mice GI tract demonstrated that pH/Time_NPs were more efficiently delivered to the inflamed colon than pH_NPs were. Compared to the single pH_NPs-treated group, the pH/Time_NPs-treated group showed increased body weight and colon length and markedly decreased disease activity index, colon weight/length ratios, histological damage, and inflammatory cell infiltration in colon tissue. Our results demonstrate that the dual pH/time-dependent NPs are an effective oral colon-targeted delivery system for colitis therapy. PMID:26229440

  17. Colon-targeted delivery of budesonide using dual pH- and time-dependent polymeric nanoparticles for colitis therapy.

    PubMed

    Naeem, Muhammad; Choi, Moonjeong; Cao, Jiafu; Lee, Yujeong; Ikram, Muhammad; Yoon, Sik; Lee, Jaewon; Moon, Hyung Ryong; Kim, Min-Soo; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Single pH-dependent drug delivery systems have been widely used for colon-targeted delivery, but their efficiency is often hampered by the variation in gut pH. To overcome the limitation of single pH-dependent delivery systems, in this study, we developed and evaluated the therapeutic potential of budesonide-loaded dual pH/time-dependent nanoparticles (NPs) for the treatment of colitis. Eudragit FS30D was used as a pH-dependent polymer, and Eudragit RS100 as a time-dependent controlled release polymer. Single pH-dependent NPs (pH_NPs), single time-dependent NPs (Time_NPs), and dual pH/time-dependent NPs (pH/Time_NPs) were prepared using the oil-in-water emulsion method. The physicochemical properties and drug release profiles of these NPs in gastrointestinal (GI) tract conditions were investigated. The therapeutic potential and in vivo distribution of the NPs were evaluated in a dextran sulfate sodium (DSS)-induced colitis mice model. The pH/Time_NPs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. The in vivo distribution study in the mice GI tract demonstrated that pH/Time_NPs were more efficiently delivered to the inflamed colon than pH_NPs were. Compared to the single pH_NPs-treated group, the pH/Time_NPs-treated group showed increased body weight and colon length and markedly decreased disease activity index, colon weight/length ratios, histological damage, and inflammatory cell infiltration in colon tissue. Our results demonstrate that the dual pH/time-dependent NPs are an effective oral colon-targeted delivery system for colitis therapy. PMID:26229440

  18. IDO1 Metabolites Activate β-catenin Signaling to Promote Cancer Cell Proliferation and Colon Tumorigenesis in Mice

    PubMed Central

    Thaker, Ameet I.; Rao, M Suprada; Bishnupuri, Kumar S.; Kerr, Thomas A; Foster, Lynne; Marinshaw, Jeffrey M.; Newberry, Rodney D.; Stenson, William F.; Ciorba, Matthew A

    2013-01-01

    BACKGROUND & AIMS Indoleamine 2,3 dioxygenase-1 (IDO1) catabolizes tryptophan along the kynurenine pathway. Though IDO1 is expressed in inflamed and neoplastic epithelial cells of the colon, its role in colon tumorigenesis is not well understood. We used genetic and pharmacologic approaches to manipulate IDO1 activity in mice with colitis-associated cancer and human colon cancer cell lines. METHODS C57Bl6 wild type (control), IDO1−/−, Rag1−/−, Rag1/IDO1 double knockout mice were exposed to azoxymethane and dextran sodium sulfate (DSS) to induce colitis and tumorigenesis. Colitis severity was assessed by measurements of disease activity, cytokine levels and histologic analysis. In vitro experiments were conducted using HCT116 and HT29 human colon cancer cells. 1-methyl tryptophan and small interfering RNA were used to inhibit IDO1. Kynurenine pathway metabolites were used to simulate IDO1 activity. RESULTS C57Bl6 mice given pharmacologic inhibitors of IDO1 and IDO1−/− mice had lower tumor burdens and reduced proliferation in the neoplastic epithelium following administration of DSS and azoxymethane than control mice. These reductions were also observed in Rag1/IDO1 double knockout mice compared to Rag1−/− mice (which lack mature adaptive immunity). In human colon cancer cells, blockade of IDO1 activity reduced nuclear and activated β-catenin, transcription of its target genes (cyclin D1 and Axin2), and ultimately proliferation. Exogenous administration of IDO1 pathway metabolites kynurenine and quinolinic acid led to activation of β-catenin and proliferation of human colon cancer cells, and increased tumor growth in mice. CONCLUSIONS IDO1, which catabolizes tryptophan, promotes colitis-associated tumorigenesis in mice, independent of its ability to limit T-cell mediated immune surveillance. The epithelial cell-autonomous survival advantage provided by IDO1 to colon epithelial cells indicate its potential as a therapeutic target. PMID:23669411

  19. Colonic lymphangiomatosis associated with anemia

    PubMed Central

    Chung, Woo Chul; Kim, Hye-Kang; Yoo, Jin Young; Lee, Jeong Rok; Lee, Kang-Moon; Paik, Chang Nyol; Jang, U-Im; Yang, Jin Mo

    2008-01-01

    Lymphangioma is an uncommon malformation of lymphatic system. Multiple colonic lymphangioma named as lymphangiomatosis is considered an extremely rare disease. Although lymphangioma is a benign tumor and most colonic lymphangiomas do not cause symptoms and do not require treatment, resection of lymphangioma is necessary in the presence of symptoms such as abdominal pain, bleeding, intussusceptions. We report a case of colonic lymphangiomatosis in a man who presented with abdominal discomfort and anemia, which was diagnosed and treated with endoscopic snare polypectomy. PMID:18837097

  20. Fungal infection of the colon

    PubMed Central

    Praneenararat, Surat

    2014-01-01

    Fungi are pathogens that commonly infect immunocompromised patients and can affect any organs of the body, including the colon. However, the literature provides limited details on colonic infections caused by fungi. This article is an intensive review of information available on the fungi that can cause colon infections. It uses a comparative style so that its conclusions may be accessible for clinical application. PMID:25364269

  1. Use of the lectin from Amaranthus caudatus as a histochemical probe of proliferating colonic epithelial cells.

    PubMed

    Boland, C R; Chen, Y F; Rinderle, S J; Resau, J H; Luk, G D; Lynch, H T; Goldstein, I J

    1991-01-15

    A newly isolated lectin, Amaranthus caudatus agglutinin (also called amaranthin or ACA), which binds to the Thomsen-Friedenreich antigen (T-antigen) and its sialylated variants, was used as a histochemical probe for proliferating cells in sections of human colonic tissues. Binding inhibition studies revealed that ACA binds to different sites on histological sections when compared to peanut agglutinin, which also recognizes the T-antigen. ACA bound selectively to the cells at the base of the colonic crypt [46 +/- 4% (SEM) of glands] which is the zone of proliferation in this tissue and preferentially labeled cytoplasmic and apical membrane glycoconjugates. Only 7 +/- 2% of the upper portions of the colonic crypts were labeled (P less than 0.001 compared to the base), and this was largely a result of extensive labeling in 2 of 23 samples studies. A marked increase in histochemical labeling by ACA was seen in adenomatous polyps and adenocarcinomas of the colon, in which 82 +/- 7 and 97 +/- 2% of the glandular units were labeled, respectively. Transitional mucosa and connective tissue adjacent to cancers were also labeled by ACA. Neuraminidase studies indicated that removal of sialic acid residues enhanced binding by peanut agglutinin, but not ACA, to glycoconjugates in cancer specimens. Specimens of colonic tissue from patients with familial adenomatous polyposis (FAP) were examined with ACA; 83 +/- 7% of adenomatous glands and 60 +/- 7% of glands in flat, normal-appearing tissue were labeled. Colonic tissues from persons at 50% risk for hereditary nonpolyposis colorectal cancer (HNPCC), FAP, and normal colons were studied and given "weighted average" labelling scores that ranged from 0-400 to accommodate variable intensity and distribution of labeling. Normal colons had a weighted average score of 65 +/- 33; FAP tissues had a score of 224 +/- 76 (P less than 0.001 compared to normal colon) and HNPCC tissues had a score of 74 +/- 70 (P less than 0.05 compared to

  2. Dual-axes confocal reflectance microscope for distinguishing colonic neoplasia

    PubMed Central

    Liu, Jonathan T. C.; Mandella, Michael J.; Friedland, Shai; Soetikno, Roy; Crawford, James M.; Contag, Christopher H.; Kino, Gordon S.; Wang, Thomas D.

    2007-01-01

    A dual-axes confocal reflectance microscope has been developed that utilizes a narrowband laser at 1310 nm to achieve high axial resolution, image contrast, field of view, and tissue penetration for distinguishing among normal, hyperplastic, and dysplastic colonic mucosa ex vivo. Light is collected off-axis using a low numerical aperture objective to obtain vertical image sections, with 4- to 5-μm resolution, at tissue depths up to 610 μm. Post-objective scanning enables a large field of view (610 × 640 μm), and balanced-heterodyne detection provides sensitivity to collect vertical sections at one frame per second. System optics are optimized to effectively reject out-of-focus scattered light without use of a low-coherence gate. This design is scalable to millimeter dimensions, and the results demonstrate the potential for a miniature instrument to detect precancerous tissues, and hence to perform in vivo histopathology. PMID:17092168

  3. Transcriptome Profiling of Human Ulcerative Colitis Mucosa Reveals Altered Expression of Pathways Enriched in Genetic Susceptibility Loci

    PubMed Central

    Li, Jin; Zhu, Junfei; Gu, Mengnan; Baldassano, Robert N.; Grant, Struan F. A.; Hakonarson, Hakon

    2014-01-01

    Human colonic mucosa altered by inflammation due to ulcerative colitis (UC) displays a drastically altered pattern of gene expression compared with healthy tissue. We aimed to understand the underlying molecular pathways influencing these differences by analyzing three publically-available, independently-generated microarray datasets of gene expression from endoscopic biopsies of the colon. Gene set enrichment analysis (GSEA) revealed that all three datasets share 87 gene sets upregulated in UC lesions and 8 gene sets downregulated (false discovery rate <0.05). The upregulated pathways were dominated by gene sets involved in immune function and signaling, as well as the control of mitosis. We applied pathway analysis to genotype data derived from genome-wide association studies (GWAS) of UC, consisting of 5,584 cases and 11,587 controls assembled from eight European-ancestry cohorts. The upregulated pathways derived from the gene expression data showed a highly significant overlap with pathways derived from the genotype data (33 of 56 gene sets, hypergeometric P = 1.49×10–19). This study supports the hypothesis that heritable variation in gene expression as measured by GWAS signals can influence key pathways in the development of disease, and that comparison of genetic susceptibility loci with gene expression signatures can differentiate key drivers of inflammation from secondary effects on gene expression of the inflammatory process. PMID:24788701

  4. Enhanced colonic tumorigenesis in alkaline sphingomyelinase (NPP7) knockout mice.

    PubMed

    Chen, Ying; Zhang, Ping; Xu, Shu-Chang; Yang, Liping; Voss, Ulrikke; Ekblad, Eva; Wu, Yunjin; Min, Yalan; Hertervig, Erik; Nilsson, Åke; Duan, Rui-Dong

    2015-01-01

    Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and inactivates platelet-activating factor (PAF) and was previously suggested to have anticancer properties. The direct evidence is still lacking. We studied colonic tumorigenesis in alk-SMase knockout (KO) mice. Formation of aberrant crypt foci (ACF) was examined after azoxymethane (AOM) injection. Tumor was induced by AOM alone, a conventional AOM/dextran sulfate sodium (DSS) treatment, and an enhanced AOM/DSS method. β-Catenin was determined by immunohistochemistry, PAF levels by ELISA, and sphingomyelin metabolites by mass spectrometry. Without treatment, spontaneous tumorigenesis was not identified but the intestinal mucosa appeared thicker in KO than in wild-type (WT) littermates. AOM alone induced more ACF in KO mice but no tumors 28 weeks after injection. However, combination of AOM/DSS treatments induced colonic tumors and the incidence was significantly higher in KO than in WT mice. By the enhanced AOM/DSS method, tumor number per mouse increased 4.5 times and tumor size 1.8 times in KO compared with WT mice. Although all tumors were adenomas in WT mice, 32% were adenocarcinomas in KO mice. Compared with WT mice, cytosol expression of β-catenin was significantly increased and nuclear translocation in tumors was more pronounced in KO mice. Lipid analysis showed decreased ceramide in small intestine and increased sphingosine-1-phosphate (S1P) in both small intestine and colon in nontreated KO mice. PAF levels in feces were significantly higher in the KO mice after AOM/DSS treatment. In conclusion, lack of alk-SMase markedly increases AOM/DSS-induced colonic tumorigenesis associated with decreased ceramide and increased S1P and PAF levels. PMID:25381265

  5. Aldosterone induces myofibroblast EGF secretion to regulate epithelial colonic permeability.

    PubMed

    Miró, Lluïsa; Pérez-Bosque, Anna; Maijó, Mònica; Amat, Concepció; Naftalin, Richard J; Moretó, Miquel

    2013-05-01

    In vivo studies show that raised aldosterone (Aldo) during low-Na adaptation regulates the growth of pericryptal myofibroblasts and reduces the permeability of the colonic epithelium. The aim of this study was to reproduce in vitro the in vivo condition of increased Aldo using human CCD-18Co myofibroblasts and T84 colonic epithelial cells to measure myofibroblast and epithelial proliferation and the expression of intercellular junction proteins. Proliferation was quantified by measuring 5-bromo-2'-deoxyuridine incorporation. The myofibroblast expression of EGF, VEGFa, and transforming growth factor-β1 (TGF-β1) was measured by real-time PCR and the expression of junctional complex proteins by Western blot. Aldo stimulated the proliferation of myofibroblasts by 70% (P < 0.05) and increased EGF mRNA expression by 30% (P < 0.05) without affecting VEGFa and TGF-β1. EGF concentration in the incubation medium increased by 30% (P < 0.05) 24 h after Aldo addition, and these effects were prevented by the addition of spironolactone. Myofibroblast proliferation in response to Aldo was mediated by EGF receptor (EGFR) and involved both MAPKK and phosphatidylinositol 3-kinase pathways. When T84 cells were incubated with medium from myofibroblasts stimulated with Aldo (conditioned medium), the expression of β-catenin and claudin IV was increased by 30% (P < 0.05) and proliferation by 40% (P < 0.05). T84 proliferation decreased when α-EGF, or the EGFR antagonist AG1478, was present. Results in vivo indicate that rats fed a low-salt diet showed an increased expression of EGF and EGFR in the colonic mucosa. These results support the view that changes in colonic permeability during low-Na adaptation are mediated by the EGF secreted by myofibroblasts in response to raised Aldo. PMID:23467299

  6. From morphology to biochemical state – intravital multiphoton fluorescence lifetime imaging of inflamed human skin

    PubMed Central

    Huck, Volker; Gorzelanny, Christian; Thomas, Kai; Getova, Valentina; Niemeyer, Verena; Zens, Katharina; Unnerstall, Tim R.; Feger, Julia S.; Fallah, Mohammad A.; Metze, Dieter; Ständer, Sonja; Luger, Thomas A.; Koenig, Karsten; Mess, Christian; Schneider, Stefan W.

    2016-01-01

    The application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of inflammatory skin diseases. In the present study, we combined multiphoton-based intravital tomography (MPT) and fluorescence lifetime imaging (MPT-FLIM) within the scope of a clinical trial of atopic dermatitis with the aim of providing personalised data on the aetiopathology of inflammation in a non-invasive manner at patients’ bedsides. These ‘optical biopsies’ generated via MPT were morphologically analysed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Two independent morphometric algorithms reliably showed an even distribution in healthy skin and a perinuclear accumulation in inflamed skin. Moreover, using MPT-FLIM, detection of the onset and progression of inflammatory processes could be achieved. In conclusion, the change in the distribution of mitochondria upon inflammation and the verification of an altered cellular metabolism facilitate a better understanding of inflammatory skin diseases and may permit early diagnosis and therapy. PMID:27004454

  7. In the eye of the neutrophil swarm-navigation signals that bring neutrophils together in inflamed and infected tissues.

    PubMed

    Lämmermann, Tim

    2016-07-01

    Neutrophils are sentinel cells that express in higher vertebrates >30 chemokine and chemoattractant receptors to sense and quickly react to tissue damage signals. Intravital microscopy studies in mouse models of wounding, inflammation, and infection have revealed that neutrophils form cell swarms at local sites of tissue injury and cell death. This swarming response is choreographed by chemokines, lipids, and other chemoattractants, controlling sequential phases of highly coordinated chemotaxis, intercellular signal relay, and cluster formation among neutrophils. This review will give a brief overview about the basic principles and key molecules that have led to the refined multistep model of how neutrophils come together to isolate sites of tissue injury and microbial invasion from healthy tissue. Whereas auto- and paracrine signaling among neutrophils during later phases of swarming can provide a level of self-organization for robust navigation in diverse inflammatory settings, guidance factors from primary tissue lesions, resident bystander cells, and dying cells regulate the initial phases of the swarming response. This review will discuss how the specific environmental context and mixture of attractants at the locally inflamed site can lead to variants of the multistep attraction model and influence the extent of neutrophil swarming, ranging from accumulations of only few individual cells to the aggregation of several hundreds of neutrophils, as found in abscesses. Given the critical roles of neutrophils in both host protection and tissue destruction, novel insights on neutrophil swarming might provide useful for the therapeutic modulation of neutrophil-dependent inflammatory processes. PMID:26416718

  8. Self-Antigen Presentation by Keratinocytes in the Inflamed Adult Skin Modulates T-Cell Auto-Reactivity.

    PubMed

    Meister, Michael; Tounsi, Amel; Gaffal, Evelyn; Bald, Tobias; Papatriantafyllou, Maria; Ludwig, Julia; Pougialis, Georg; Bestvater, Felix; Klotz, Luisa; Moldenhauer, Gerhard; Tüting, Thomas; Hämmerling, Günter J; Arnold, Bernd; Oelert, Thilo

    2015-08-01

    Keratinocytes have a pivotal role in the regulation of immune responses, but the impact of antigen presentation by these cells is still poorly understood, particularly in a situation where the antigen will be presented only in adult life. Here, we generated a transgenic mouse model in which keratinocytes exclusively present a myelin basic protein (MBP) peptide covalently linked to the major histocompatibility complex class II β-chain, solely under inflammatory conditions. In these mice, inflammation caused by epicutaneous contact sensitizer treatment resulted in keratinocyte-mediated expansion of MBP-specific CD4(+) T cells in the skin. Moreover, repeated contact sensitizer application preceding a systemic MBP immunization reduced the reactivity of the respective CD4(+) T cells and lowered the symptoms of the resulting experimental autoimmune encephalomyelitis. This downregulation was CD4(+) T-cell-mediated and dependent on the presence of the immune modulator Dickkopf-3. Thus, presentation of a neo self-antigen by keratinocytes in the inflamed, adult skin can modulate CD4(+) T-cell auto-aggression at a distal organ. PMID:25835957

  9. Local T/B cooperation in inflamed tissues is supported by T follicular helper-like cells.

    PubMed

    Vu Van, Dana; Beier, Katja C; Pietzke, Lea-Jean; Al Baz, Maysun S; Feist, Randi K; Gurka, Stephanie; Hamelmann, Eckard; Kroczek, Richard A; Hutloff, Andreas

    2016-01-01

    Autoimmune diseases and other inflammatory conditions are characterized by large lymphocytic tissue infiltrates in which T and B cells can be found in close contact. Here, using a murine airway inflammation model, we compare antigen-specific T and B cells in lung tissue versus lung-draining lymph node. In the lung we identify a B-cell population exhibiting a classical germinal centre phenotype without being organized into ectopic lymphoid tissue. By contrast, classical CXCR5(+) Bcl-6(+) T follicular helper cells are not present. Nevertheless, lung-infiltrating T cells exhibit follicular helper-like properties including the potential to provide help to naive B cells. The lung tissue is also a survival niche for memory T and B cells remaining in residual peribronchial infiltrates after resolution of inflammation. Collectively, this study shows the importance of T/B cooperation not only in lymph nodes but also in inflamed peripheral tissues for local antibody responses to infection and autoimmunity. PMID:26915335

  10. Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force

    PubMed Central

    Morikis, Vasilios A.; Radecke, Chris; Jiang, Yanyan; Heinrich, Volkmar; Curry, Fitz-Roy; Simon, Scott I.

    2016-01-01

    BACKGROUND Recombinant atrial natriuretic peptide (ANP) is administered in patients with acute heart failure in Japan to improve renal function and hemodynamics, but its anti-inflammatory effect on activated leukocytes may also contribute to its therapeutic efficacy. OBJECTIVE Examine unconventional role of ANP in neutrophil adhesion to inflamed endothelium. METHODS Human neutrophils were perfused over endothelial monolayers in a microfluidic lab-chip assay. Cell rheology was assessed by micropipette aspiration to assess changes in cortical tension and viscosity. Fluorescence microscopy was applied to measure adhesive contact area and β2-integrin focal bond formation. RESULTS ANP inhibited neutrophil rolling and firm adhesion without influencing the upregulation of cellular adhesion molecules on endothelium or the regulation of high affinity CD18 and shedding of L-selectin during neutrophil activation. Exposed to fluid shear, integrin mediated arrest was disrupted with ANP treatment, which elicited formation of long tethers and diminished cell spreading and contact. This correlated with a ~40% increase in neutrophil viscosity and a reduction in the adhesive footprint. CONCLUSIONS A decrease in cell deformation and neutrophil flattening with ANP results in fewer integrin bond clusters, which translates to higher tensile forces and impaired adhesion strengthening and cell detachment. PMID:26639357

  11. From morphology to biochemical state – intravital multiphoton fluorescence lifetime imaging of inflamed human skin

    NASA Astrophysics Data System (ADS)

    Huck, Volker; Gorzelanny, Christian; Thomas, Kai; Getova, Valentina; Niemeyer, Verena; Zens, Katharina; Unnerstall, Tim R.; Feger, Julia S.; Fallah, Mohammad A.; Metze, Dieter; Ständer, Sonja; Luger, Thomas A.; Koenig, Karsten; Mess, Christian; Schneider, Stefan W.

    2016-03-01

    The application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of inflammatory skin diseases. In the present study, we combined multiphoton-based intravital tomography (MPT) and fluorescence lifetime imaging (MPT-FLIM) within the scope of a clinical trial of atopic dermatitis with the aim of providing personalised data on the aetiopathology of inflammation in a non-invasive manner at patients’ bedsides. These ‘optical biopsies’ generated via MPT were morphologically analysed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Two independent morphometric algorithms reliably showed an even distribution in healthy skin and a perinuclear accumulation in inflamed skin. Moreover, using MPT-FLIM, detection of the onset and progression of inflammatory processes could be achieved. In conclusion, the change in the distribution of mitochondria upon inflammation and the verification of an altered cellular metabolism facilitate a better understanding of inflammatory skin diseases and may permit early diagnosis and therapy.

  12. Local T/B cooperation in inflamed tissues is supported by T follicular helper-like cells

    PubMed Central

    Vu Van, Dana; Beier, Katja C.; Pietzke, Lea-Jean; Al Baz, Maysun S.; Feist, Randi K.; Gurka, Stephanie; Hamelmann, Eckard; Kroczek, Richard A.; Hutloff, Andreas

    2016-01-01

    Autoimmune diseases and other inflammatory conditions are characterized by large lymphocytic tissue infiltrates in which T and B cells can be found in close contact. Here, using a murine airway inflammation model, we compare antigen-specific T and B cells in lung tissue versus lung-draining lymph node. In the lung we identify a B-cell population exhibiting a classical germinal centre phenotype without being organized into ectopic lymphoid tissue. By contrast, classical CXCR5+ Bcl-6+ T follicular helper cells are not present. Nevertheless, lung-infiltrating T cells exhibit follicular helper-like properties including the potential to provide help to naive B cells. The lung tissue is also a survival niche for memory T and B cells remaining in residual peribronchial infiltrates after resolution of inflammation. Collectively, this study shows the importance of T/B cooperation not only in lymph nodes but also in inflamed peripheral tissues for local antibody responses to infection and autoimmunity. PMID:26915335

  13. Bone marrow dendritic cell progenitors sense pathogens via Toll-like receptors and subsequently migrate to inflamed lymph nodes.

    PubMed

    Schmid, Michael A; Takizawa, Hitoshi; Baumjohann, Dior R; Saito, Yasuyuki; Manz, Markus G

    2011-11-01

    Common dendritic cell progenitors (CDPs) in the bone marrow (BM) regenerate dendritic cells (DCs) in lymphoid and nonlymphoid tissues. How the dissemination of progenitor-derived DCs to peripheral tissues is regulated on need remains elusive. Microbes are sensed by pathogen recognition receptors such as Toll-like receptors (TLRs). We found that CDPs in the BM express TLR2, TLR4, and TLR9. On TLR stimulation, CDPs down-regulated CXCR4, the nonredundant chemokine receptor for their BM retention, up-regulated CCR7, and migrated to lymph nodes (LNs). When TLR agonists were injected locally, CDPs preferentially gave rise to DCs in inflamed LNs in expense of noninflamed LNs and the BM, but they did not alter their lineage differentiation and proliferative activity. Consequently, BM DC progenitors can sense TLR agonists and, via regulation of CXCR4 and CCR7, support the replenishment of DCs in reactive LNs. This mechanism likely developed to support DC homeostasis on specific need at sites of inflammation. PMID:21908421

  14. The prostaglandin D2 receptor CRTH2 regulates accumulation of group 2 innate lymphoid cells in the inflamed lung

    PubMed Central

    Tait Wojno, ED; Monticelli, LA; Tran, SV; Alenghat, T; Osborne, LC; Thome, JJ; Willis, C; Budelsky, A; Farber, DL; Artis, D

    2015-01-01

    Group 2 innate lymphoid cells (ILC2s) promote type 2 cytokine-dependent immunity, inflammation and tissue repair. While epithelial cell-derived cytokines regulate ILC2 effector functions, the pathways that control the in vivo migration of ILC2s into inflamed tissues remain poorly understood. Here, we provide the first demonstration that expression of the prostaglandin D2 (PGD2) receptor CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cells) regulates the in vivo accumulation of ILC2s in the lung. While a significant proportion of ILC2s isolated from healthy human peripheral blood expressed CRTH2, a smaller proportion of ILC2s isolated from non-diseased human lung expressed CRTH2, suggesting that dynamic regulation of CRTH2 expression might be associated with the migration of ILC2s into tissues. Consistent with this, murine ILC2s expressed CRTH2, migrated towards PGD2 in vitro and accumulated in the lung in response to PGD2 in vivo. Further, mice deficient in CRTH2 exhibited reduced ILC2 responses and inflammation in a murine model of helminth-induced pulmonary type 2 inflammation. Critically, adoptive transfer of CRTH2-sufficient ILC2s restored pulmonary inflammation in CRTH2-deficient mice. Together, these data identify a role for the PGD2-CRTH2 pathway in regulating the in vivo accumulation of ILC2s and the development of type 2 inflammation in the lung. PMID:25850654

  15. Potential role of Escherichia coli DNA mismatch repair proteins in colon cancer.

    PubMed

    Khan, Shahanavaj

    2015-12-01

    The epithelium of gastrointestinal tract organizes many innate defense systems against microbial intruders such as integrity of epithelial, rapid eviction of infected cells, quick turnover of epithelial cell, intrinsic immune responses and autophagy. However, Enteropathogenic Escherichia coli (EPEC) are equipped with well developed infectious tricks that evade the host defense systems and utilize the gastrointestinal epithelium as a multiplicative foothold. During multiplication on and within the epithelium, EPEC secrete various toxins that can weaken, usurp, and use many host cellular systems. However, the possible mechanisms of pathogenesis are still poorly elusive. Recent study reveals the existence of EPEC in colorectal cancer patients and their potential role in depletion of DNA mismatch repair (MMR) proteins of host cell in colonic cell lines. The EPEC colonised intracellularly in colon mucosa of colorectal carcinoma whereas extracellular strain was detected in mucosa of normal colon cells. Interestingly, alteration in MutS, MutL complexes and MUTYH of mammalian cells may be involved in development of CRC. These data propose that MMR of E. coli may be potential therapeutic targets and early detection biomarkers for CRC. This article reviews the potential role of E. coli MutS, MutL and MutY protein in CRC aetiology. PMID:26014615

  16. The differential frequency of Lineage(-)CRTH2(-)CD45(+)NKp44(-)CD117(-)CD127(+)ILC subset in the inflamed terminal ileum of patients with Crohn's disease.

    PubMed

    Li, Jian; Doty, Andria L; Iqbal, Atif; Glover, Sarah C

    2016-01-01

    Deregulation of various components of the immune system has been reported in the inflamed gut of Crohn's disease (CD) patients. Innate lymphoid cells (ILCs) are novel innate effector lymphocytes which can rapidly respond to danger signals, from invading pathogens or tissue damage, to maintain homeostasis, especially along the mucosal surfaces. The purpose of this study is to compare composition of the intestinal ILCs subsets of CD patients with differential inflammatory conditions of the terminal ileum, which are marked by distinct histological appearances and mucosal profiles of cytokines. We observed alterations in the frequency of Lineage(-)CRTH2(-)CD45(+)NKp44(-)CD117(-)CD127(+)ILC subset in the inflamed terminal ileum. PMID:27215784

  17. Pathways to Colonization

    NASA Technical Reports Server (NTRS)

    Smitherman, David V., Jr.

    2003-01-01

    The steps required for space colonization are many to grow from our current 3-person International Space Station, now under construction, to an infrastructure that can support hundreds and eventually thousands of people in space. This paper will summarize the author's findings from numerous studies and workshops on related subjects and identify some of the critical next steps toward space colonization. Findings will be drawn from the author s previous work on space colony design, space infrastructure workshops, and various studies that addressed space policy. In conclusion, this paper will note that significant progress has been made on space facility construction through the International Space Station program, and that significant efforts are needed in the development of new reusable Earth to Orbit transportation systems. The next key steps will include reusable in space transportation systems supported by in space propellant depots, the continued development of inflatable habitat and space elevator technologies, and the resolution of policy issues that will establish a future vision for space development.

  18. Allogeneic Murine Mesenchymal Stem Cells: Migration to Inflamed Joints In Vivo and Amelioration of Collagen Induced Arthritis When Transduced to Express CTLA4Ig

    PubMed Central

    Barry, Frank; Ritter, Thomas; O'Flatharta, Cathal; Howard, Linda; Shaw, Georgina; Anegon, Ignacio; Murphy, Mary

    2013-01-01

    Despite the immunosuppressive, homing, and regenerative capabilities of mesenchymal stem cells (MSCs), their ability to migrate to arthritic joints and influence the course of arthritis in vivo remains poorly understood. The objective of this study was to determine if allogeneic MSCs migrate to inflamed joints in vivo and to determine if MSCs expressing the costimulation blocker cytotoxic T lymphocyte associated antigen-4 coupled to immunoglobulin-G (CTLA4Ig) could be used to ameliorate collagen induced arthritis (CIA). The migration of systemically delivered inbred mouse strain (FVB) MSCs to migrate to inflamed joints in CIA was studied using real-time quantitative polymerase chain reaction. Furthermore, the effect of BALB/c MSCs modified with an adenoviral vector to express CTLA4Ig, on T cell function in vitro and on CIA in vivo was assessed. After systemic delivery of FVB MSCs, eGFP DNA was detectable in the joints of mice with CIA confirming that some MSCs had reached to inflamed joints. BALB/c MSCs suppressed the secretion of both TNFα and IFNγ, and reduced the ratio of Th1:Th2 cytokine expression, by DBA/1 T cells in vitro irrespective of viral modification. The expression of CTLA4Ig did not augment this effect. Despite a worsening of disease scores after infusion of BALB/c MSCs in vivo, BALB/c MSCs expressing CTLA4Ig significantly delayed the onset of inflammatory arthritis in CIA. These data demonstrate that allogeneic MSCs can migrate to the inflamed joints of CIA in vivo and that genetically modified allogeneic MSCs may be considered for development of gene therapy strategies for inflammatory arthritis PMID:23895495

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

    PubMed

    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

    2010-01-01

    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

  20. Comparison and Efficacy of LigaSure and Rubber Band Ligature in Closing the Inflamed Cecal Stump in a Rat Model of Acute Appendicitis

    PubMed Central

    Yeh, Chun-Chieh; Jan, Chia-Ing; Yang, Horng-Ren; Jeng, Long-Bin; Su, Wen-Pang

    2015-01-01

    Safety of either LigaSure or rubber band in closing inflamed appendiceal stump in acute appendicitis has been less investigated. In this study, cecal ligation followed by resecting inflamed cecum was performed to mimic appendectomy in a rat model of acute appendicitis. Rats were sacrificed immediately (Group A) and 7 days (Group B) after cecal resection, respectively. The cecal stumps were closed by silk ligature (S), 5 mm LigaSure (L), or rubber band (R). Seven days after cecal resection, the LigaSure (BL) and silk subgroups (BS) had significantly less intra-abdominal adhesion and better laparotomy wound healing than rubber band subgroup (BR). The initial bursting pressure at cecal stump was comparable among the three methods; along with tissue healing process, both BL and BS provided a higher bursting pressure than BR 7 days after appendectomy. BL subgroup had more abundant hydroxyproline deposition than BS and BR subgroup. Furthermore, serum TNF-α in BR group kept persistently increasing along with time after cecal resection. Thus, the finding that LigaSure but not rubber band is safe in sealing off the inflamed cecal stump in rat model of acute appendicitis suggests the possibility of applying LigaSure for appendectomy via single port procedure or natural orifice transluminal endoscopic surgery (NOTES). PMID:25699264

  1. Comparison and efficacy of LigaSure and rubber band ligature in closing the inflamed cecal stump in a rat model of acute appendicitis.

    PubMed

    Yeh, Chun-Chieh; Jan, Chia-Ing; Yang, Horng-Ren; Huang, Po-Han; Jeng, Long-Bin; Su, Wen-Pang; Chen, Hui-Chen

    2015-01-01

    Safety of either LigaSure or rubber band in closing inflamed appendiceal stump in acute appendicitis has been less investigated. In this study, cecal ligation followed by resecting inflamed cecum was performed to mimic appendectomy in a rat model of acute appendicitis. Rats were sacrificed immediately (Group A) and 7 days (Group B) after cecal resection, respectively. The cecal stumps were closed by silk ligature (S), 5 mm LigaSure (L), or rubber band (R). Seven days after cecal resection, the LigaSure (BL) and silk subgroups (BS) had significantly less intra-abdominal adhesion and better laparotomy wound healing than rubber band subgroup (BR). The initial bursting pressure at cecal stump was comparable among the three methods; along with tissue healing process, both BL and BS provided a higher bursting pressure than BR 7 days after appendectomy. BL subgroup had more abundant hydroxyproline deposition than BS and BR subgroup. Furthermore, serum TNF-α in BR group kept persistently increasing along with time after cecal resection. Thus, the finding that LigaSure but not rubber band is safe in sealing off the inflamed cecal stump in rat model of acute appendicitis suggests the possibility of applying LigaSure for appendectomy via single port procedure or natural orifice transluminal endoscopic surgery (NOTES). PMID:25699264

  2. Increased apoptosis in gastric mucosa adjacent to intestinal metaplasia

    PubMed Central

    van Grieken, N C T; Meijer, G A; zur Hausen, A; Meuwissen, S G M; Baak, J P A; Kuipers, E J

    2003-01-01

    Background: The biological processes involved in the development of gastric mucosal atrophy and intestinal metaplasia are still incompletely understood. Reports testing the hypothesis that apoptosis leads to atrophy have yielded conflicting results. The availability of new antibodies for the detection of apoptotic cells in tissue sections has facilitated the analysis of the role of apoptosis in the gastritis–atrophy–intestinal metaplasia sequence. Methods: Archival material from 40 gastric resection specimens with normal mucosa (n = 5), chronic active gastritis (n = 17), or intestinal metaplasia (n = 18) was studied. Immunohistochemistry was performed using antibodies directed against cleaved cytokeratin 18 and active caspase 3. Slides were scored on a 0–3 scale for the presence of apoptotic cells. Results: Normal gastric mucosa contained low numbers of apoptotic cells at the surface epithelium (mean score, 0.20). This number was significantly increased in cases with chronic gastritis (mean score, 1.06) and in those with intestinal metaplasia (mean score, 2.56). Within the intestinal metaplasia cases, 44 different foci of intestinal metaplasia were identified. In 39 of these 44 areas, concentrations of apoptotic cells were seen immediately adjacent to the foci of intestinal metaplasia, but not in the metaplastic epithelium itself. Conclusions: Apoptosis is uncommon in normal gastric mucosa. Chronic inflammation and intestinal metaplasia are associated with increased apoptosis, but occur mainly at the mucosal surface and not in the deeper layers. These findings do not support the concept that apoptosis underlies the loss of gastric glands and leads to atrophy, but the observed concentration of apoptotic epithelial cells adjacent to foci of intestinal metaplasia could be related to heterogeneity of epithelial damage, causing apoptosis, to which intestinal metaplasia is a response. PMID:12719456

  3. Hereditary and Familial Colon Cancer

    PubMed Central

    Jasperson, Kory W.; Tuohy, Thérèse M.; Neklason, Deborah W.; Burt, Randall W.

    2011-01-01

    Between 2% to 5% of all colon cancers arise in the setting of well defined inherited syndromes, including Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, and certain hamartomatous polyposis conditions. Each is associated with a high risk of colon cancer. In addition to the syndromes, up to one-third of colon cancers exhibit increased familial risk, likely related to inheritance. A number of less penetrant, but possibly more frequent susceptibility genes have been identified for this level of inheritance. Clarification of predisposing genes allows for accurate risk assessment and more precise screening approaches. This review examines the colon cancer syndromes, their genetics and management, and also the common familial colon cancers with current genetic advances and screening guidelines. PMID:20420945

  4. Schwannoma of the sigmoid colon.

    PubMed

    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 lumen of the sigmoid colon was seen and biopsies were taken. Histopathological examination indicated a suspicion of gastrointestinal tumour and the patient underwent sigmoid colon resection after preoperative evaluation by laboratory analysis, abdominal ultrasonography and CT. Her postoperative course was uneventful and she was discharged on the fifth day for outpatient control. The histopathology report revealed schwannoma of the sigmoid colon. This was a case of schwannoma of the sigmoid colon that was successfully treated with total resection. PMID:25976197

  5. Design of sensors for microcirculation investigation in pharyngeal mucosa

    NASA Astrophysics Data System (ADS)

    Mareew, Gleb O.; Mareew, Oleg V.; Fedosov, Ivan V.; Tuchin, Valery V.

    2004-08-01

    Sensors designed for research of blood microcirculation in pharyngeal mucosa by a laser Doppler flowmetry, are described and considered in view of anatomic and physiological features of objects of research. Two designs of sensors for laser Doppler flowmetry are described - non-contact and contact. The results of and clinical testing at norm and different pathologies of pharynx of on calibration of sensors, and also their comparative technical characteristics and materials of clinical researches of microcirculation are resulted at norm and at a various pathology.

  6. Autoimmune enteropathy: not all flat mucosa mean coeliac disease

    PubMed Central

    Volta, Umberto; Mumolo, Maria Gloria; Caio, Giacomo; Boschetti, Elisa; Latorre, Rocco; Giancola, Fiorella; Paterini, Paola; Giorgio, Roberto De

    2016-01-01

    A 62-year-old woman complaining of severe malabsorption was diagnosed with celiac disease based on the findings of flat, small intestinal mucosa and HLA-DQ2 positivity, although celiac serology was negative. This diagnosis was questioned due to the lack of clinical and histological improvement after a long period of strict gluten-free diet. The detection of enterocyte autoantibodies guided to the correct diagnosis of autoimmune enteropathy, leading to a complete recovery of the patient following an appropriate immunosuppressive treatment. Autoimmune enteropathy should be considered in the differential diagnosis of malabsorption with severe villous atrophy, including those cases with negative celiac-related serology. PMID:27099674

  7. Extensive amalgam tattoo on the alveolar-gingival mucosa.

    PubMed

    Galletta, Vivian C; Artico, Gabriela; Dal Vechio, Aluana M C; Lemos Jr, Celso A; Migliari, Dante A

    2011-01-01

    Amalgam tattoos are common exogenous pigmented lesions of the oral mucosa occurring mainly by inadvertent placement of amalgam particles into soft tissues. The diagnosis of amalgam tattoo is simple, usually based on clinical findings associated with presence or history of amalgam fillings removal. Intraoral X-rays may be helpful in detecting amalgam-related radiopacity. In cases where amalgam tattoo cannot be differentiated from other causes of oral pigmentation, a biopsy should be performed. This article deals with an extensive amalgam tattoo lesion which required a biopsy for a definitive diagnosis. PMID:22147048

  8. Hydatid cyst of the buccal mucosa: An unusual presentation

    PubMed Central

    Lavanya, R. M.; Kamath, V. V.; Komali, Y.; Krishnamurthy, Shruthi

    2015-01-01

    Hydatid cyst is a parasitic cyst caused by the tapeworm Echinococcus that occurs primarily in sheep grazing areas worldwide. It is a chronic disease, and the cysts can be localized in unusual anatomical and geographic locations. It is known to affect the head and neck region. Patients must undergo a thorough systemic investigation as 20–30% show multiorgan involvement. We report a case of hydatid cyst occurring in the buccal mucosa of a 45- year -old male presenting as a small asymptomatic lump and emphasize on its rarity and diagnostic issues. PMID:26392735

  9. Eosinophilic ulcer of oral mucosa: a case report

    PubMed Central

    Bortoluzzi, Marcelo Carlos; Passador-Santos, Fabrício; Capella, Diogo L.; Manfro, Gabriel; Nodari, Rudy José; Presta, Andréia Antoniuk

    2012-01-01

    Summary Eosinophilic Ulcer (EU) is a rare self-limiting chronic benign lesion of the oral mucosa with pathogenesis still unclear, however it may resemble malignancies, traumatic ulcerations and some infections such as deep fungal infections, tuberculosis and primary syphilis. This is a case report of a patient with EU in the lateral border of the tongue with no history of associated trauma and refractory to treatment with drugs. The ulcer rapidly healed after an incisional biopsy and the definite diagnosis was achieved only combining histologic findings and the clinical follow-up. PMID:22783449

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Electrospun Contrast-Agent-Loaded Fibers for Colon-Targeted MRI.

    PubMed

    Jin, Miao; Yu, Deng-Guang; Wang, Xia; Geraldes, Carlos F G C; Williams, Gareth R; Bligh, S W Annie

    2016-04-01

    Magnetic resonance imaging is a diagnostic tool used for detecting abnormal organs and tissues, often using Gd(III) complexes as contrast-enhancing agents. In this work, core-shell polymer fibers have been prepared using coaxial electrospinning, with the intent of delivering gadolinium (III) diethylenetriaminepentaacetate hydrate (Gd(DTPA)) selectively to the colon. The fibers comprise a poly(ethylene oxide) (PEO) core loaded with Gd(DTPA), and a Eudragit S100 shell. They are homogeneous, with distinct core-shell phases. The components in the fibers are dispersed in an amorphous fashion. The proton relaxivities of Gd(DTPA) are preserved after electrospinning. To permit easy visualization of the release of the active ingredient from the fibers, analogous materials are prepared loaded with the dye rhodamine B. Very little release is seen in a pH 1.0 buffer, while sustained release is seen at pH 7.4. The fibers thus have the potential to selectively deliver Gd(DTPA) to the colon. Mucoadhesion studies reveal there are strong adhesive forces between porcine colon mucosa and PEO from the core, and the dye-loaded fibers can be successfully used to image the porcine colon wall. The electrospun core-shell fibers prepared in this work can thus be developed as advanced functional materials for effective imaging of colonic abnormalities. PMID:26899401

  12. Growth Control in Colon Epithelial Cells: Gadolinium Enhances Calcium-Mediated Growth Regulation

    PubMed Central

    Attili, Durga; Jenkins, Brian; Aslam, Muhammad Nadeem; Dame, Michael K.

    2013-01-01

    Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1–5 µM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet. PMID:23008064

  13. The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis.

    PubMed

    Xiao, Hui; Gulen, Muhammet Fatih; Qin, Jinzhong; Yao, Jianhong; Bulek, Katarzyna; Kish, Danielle; Altuntas, Cengiz Zubeyir; Wald, David; Ma, Caixia; Zhou, Hang; Tuohy, Vincent K; Fairchild, Robert L; de la Motte, Carol; Cua, Daniel; Vallance, Bruce A; Li, Xiaoxia

    2007-04-01

    Despite constant contact with the large population of commensal bacteria, the colonic mucosa is normally hyporesponsive to these potentially proinflammatory signals. Here we report that the single immunoglobulin IL-1 receptor-related molecule (SIGIRR), a negative regulator for Toll-IL-1R signaling, plays a critical role in gut homeostasis, intestinal inflammation, and colitis-associated tumorigenesis by maintaining the microbial tolerance of the colonic epithelium. SIGIRR-deficient (Sigirr(-/-)) colonic epithelial cells displayed commensal bacteria-dependent homeostatic defects, as shown by constitutive upregulation of inflammatory genes, increased inflammatory responses to dextran sulfate sodium (DSS) challenge, and increased Azoxymethane (AOM)+DSS-induced colitis-associated tumorigenesis. Gut epithelium-specific expression of the SIGIRR transgene in the SIGIRR-deficient background reduced the cell survival of the SIGIRR-deficient colon epithelium, abrogated the hypersensitivity of the Sigirr(-/-) mice to DSS-induced colitis, and reduced AOM+DSS-induced tumorigenesis. Taken together, our results indicate that epithelium-derived SIGIRR is critical in controlling the homeostasis and innate immune responses of the colon to enteric microflora. PMID:17398123

  14. Dehydropeptidase 1 promotes metastasis through regulation of E-cadherin expression in colon cancer

    PubMed Central

    Park, Sang Yoon; Lee, Seon-Jin; Cho, Hee Jun; Kim, Tae Woo; Kim, Jong-Tae; Kim, Jae Wha; Lee, Chul-Ho; Kim, Bo-Yeon; Yeom, Young Il; Lim, Jong-Seok; Lee, Younghee; Lee, Hee Gu

    2016-01-01

    Dehydropeptidase 1 (DPEP1) is a zinc-dependent metalloproteinase that is expressed aberrantly in several cancers. The role of DPEP1 in cancer remain controversial. In this study, we demonstrate that DPEP1 functions as a positive regulator for colon cancer cell metastasis. The expression of DPEP1 mRNA and proteins were upregulated in colon cancer tissues compared to normal mucosa. Gain-of-function and loss-of-function approaches were used to examine the malignant phenotype of DPEP1-expressing or DPEP1-depleted cells. DPEP1 expression caused a significant increase in colon cancer cell adhesion and invasion in vitro, and metastasis in vivo. In contrast, DPEP1 depletion induced opposite effects. Furthermore, cilastatin, a DPEP1 inhibitor, suppressed the invasion and metastasis of DPEP1-expressing cells. DPEP1 inhibited the leukotriene D4 signaling pathway and increased the expression of E-cadherin. We also show that DPEP1 mediates TGF-β-induced EMT. TGF-β transcriptionally repressed DPEP1 expression. TGF-β treatment decreased E-cadherin expression and promoted cell invasion in DPEP1-expressing colon cancer cell lines, whereas it did not affect these parameters in DPEP1-depleted cell lines. These results suggest that DPEP1 promotes cancer metastasis by regulating E-cadherin plasticity and that it might be a potential therapeutic target for preventing the progression of colon cancer. PMID:26824987

  15. Investigation of phosphatidylcholine enhancing FITC-insulin across buccal mucosa by confocal laser scanning microscopy

    NASA Astrophysics Data System (ADS)

    Tian, Weiqun; Su, Li; Zeng, Shaoqun; Luo, Qingming; Gao, Qiuhua; Xu, Huibi

    2002-04-01

    The aim was to characterize the transport of fluorescein isothiocyanate (FITC)-labeled dextran and insulin with different resoluble compounds for peptides and proteins through buccal mucosa. The penetration rate of insulin molecules through porcine buccal mucosa (a nonkeratinized epithelium, comparable to human buccal mucosa) was investigated by measuring transbuccal fluxes and by analyzing the distribution of the fluorescent probe in the rabbit buccal mucosa epithelium, using confocal laser scanning microscopy for visualizing permeation pathways. The confocal images of the distribution pattern of FITC-dextran and FITC-insulin showed that the paracellular route is the major pathway of FITC-dextran through buccal mucosa epithelium, the intra-cellular route is the major pathway of FITC-insulin through buccal mucosa epithelium. The permeation rate can be increased by co-administration of soybean phosphatidylcholine (SPC).

  16. Colonize, evade, flourish

    PubMed Central

    Rubin, Erica J; Trent, M Stephen

    2013-01-01

    Helicobacter pylori is an adapted gastric pathogen that colonizes the human stomach, causing severe gastritis and gastric cancer. A hallmark of infection is the ability of this organism to evade detection by the human immune system. H. pylori has evolved a number of features to achieve this, many of which involve glyco-conjugates including the lipopolysaccharide, peptidoglycan layer, glycoproteins, and glucosylated cholesterol. These major bacterial components possess unique features from those of other gram-negative organisms, including differences in structure, assembly, and modification. These defining characteristics of H. pylori glycobiology help the pathogen establish a long-lived infection by providing camouflage, modulating the host immune response, and promoting virulence mechanisms. In this way, glyco-conjugates are essential for H. pylori pathogenicity and survival, allowing it to carve out a niche in the formidable environment of the human stomach. PMID:23859890

  17. [Irritable colon and constipation].

    PubMed

    Meyenberger, C

    1993-04-20

    Irritable bowel syndrome is a very common clinical problem with a broad spectrum of severity. The management includes a combination of positive diagnosis of typical symptoms with limited investigations to exclude underlying structural or biochemical disorders. Therapeutic trials focus on the relief of predominant symptoms. Identification and modification of factors exacerbating symptoms, behavioural techniques and pharmacologic agents directed to the presumed gastrointestinal motor dysfunction are required. Psychological support by the physician is the most important part of treatment. Chronic constipation may be the predominant symptom of irritable bowel syndrome. Underlying organic disorders must be excluded by clinical examination and endoscopy. Severe chronic constipation requires further investigation of colonic motility and defecation. High fibre diet, osmotic laxatives and procinetic agents may lead to an improvement. In rare cases surgery may be indicated. PMID:8488351

  18. Organoids as an ex vivo model for studying the serotonin system in the murine small intestine and colon epithelium.

    PubMed

    Tsuruta, Takeshi; Saito, Shinichi; Osaki, Yosuke; Hamada, Akihiro; Aoki-Yoshida, Ayako; Sonoyama, Kei

    2016-05-20

    Intestinal organoids were recently established as an ex vivo model of the intestinal epithelium. The present study investigated the serotonin (5-hydroxytryptamine, 5-HT) system using organoids. Organoids from murine small intestinal and colonic crypts were successfully cultured. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that small intestinal and colonic organoids express mRNAs encoding tryptophan hydroxylase-1 (TPH1) (the rate-limiting enzyme of 5-HT synthesis), serotonin reuptake transporter (SERT), 5-HT receptor (HTR)2A, HTR2B, and HTR4. SERT mRNA levels were significantly higher in the small intestine than in the colon in both the mucosal tissues and organoids, as estimated by quantitative real-time RT-PCR. Although the 5-HT concentration and levels of chromogranin A (CgA) (an enteroendocrine cell marker), TPH1, and HTR4 mRNAs were significantly higher in the colonic mucosa than the small intestinal mucosa, they were the same in small intestinal and colonic organoids. There were no significant differences in HTR2A and HTR2B mRNA levels between the small intestine and colon in either the mucosal tissues or organoids. Immunofluorescence staining showed that the number of CgA-positive cells in the colonic organoids appeared to increase upon culturing with acetate. Acetate supplementation significantly increased CgA, TPH1, and HTR4 mRNA levels in the colonic organoids. We propose that organoids are useful for investigating the 5-HT system in the intestinal epithelium, even though colonic organoids may require gut microbiota-derived factors such as short-chain fatty acids. PMID:27105910

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

    PubMed

    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. PMID:1370188

  20. Permeabilities of rebamipide via rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier

    PubMed Central

    Huang, Bei-Bei; Li, Guo-Feng; Luo, Jing-Hui; Duan, Lian; Nobuaki, Kishimoto; Akira, Yamamoto

    2008-01-01

    AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol significantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10% totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng·h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng·h/mL for chitosan capsule, 1887.9 ng·h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was co-administrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rebamipide across the jejunum, ileum and the colon, and

  1. Colon interposition for oesophageal replacement.

    PubMed

    Thomas, Pascal A; Gilardoni, Adrian; Trousse, Delphine; D'Journo, Xavier B; Avaro, Jean-Philippe; Doddoli, Christophe; Giudicelli, Roger; Fuentes, Pierre

    2009-01-01

    The choice of the colon as an oesophageal substitute results primarily from the unavailability of the stomach. However, given its durability and function, colon interposition keeps elective indications in patients with benign or malignant oesophageal disease who are potential candidates for long survival. The choice of the colonic portion used for oesophageal reconstruction depends on the required length of the graft, and the encountered colonic vascular anatomy, the last being characterised by the near-invariability of the left colonic vessels, in contrast to the vascular pattern of the right side of the colon. Accordingly, the transverse colon with all or part of the ascending colon is the substitute of choice, positioned in the isoperistaltic direction, and supplied either from the left colic vessels for long grafts or middle colic vessels for shorter grafts. Technical key points are: full mobilisation of the entire colon, identification of the main colonic vessels and collaterals, and a prolonged clamping test to ensure the permeability of the chosen nourishing pedicle. Transposition through the posterior mediastinum in the oesophageal bed is the shortest one and thereby offers the best functional results. When the oesophageal bed is not available, the retrosternal route is the preferred alternative option. The food bolus travelling mainly by gravity makes straightness of the conduit of paramount importance. The proximal anastomosis is a single-layer hand-fashioned end-to-end anastomosis to prevent narrowing. When the stomach is available, the distal anastomosis is best performed at the posterior part of the antrum for the reasons of pedicle positioning and reflux prevention, and a gastric drainage procedure is added when the oesophagus and vagus nerves have been removed. In the other cases, a Roux-en-Y jejunal loop is preferable to prevent bile reflux into the colon. Additional procedures include re-establishment of the colonic continuity, a careful closure of

  2. A Protocol for the Comprehensive Flow Cytometric Analysis of Immune Cells in Normal and Inflamed Murine Non-Lymphoid Tissues

    PubMed Central

    Yu, Yen-Rei A.; O’Koren, Emily G.; Hotten, Danielle F.; Kan, Matthew J.; Kopin, David; Nelson, Erik R.; Que, Loretta; Gunn, Michael D.

    2016-01-01

    Flow cytometry is used extensively to examine immune cells in non-lymphoid tissues. However, a method of flow cytometric analysis that is both comprehensive and widely applicable has not been described. We developed a protocol for the flow cytometric analysis of non-lymphoid tissues, including methods of tissue preparation, a 10-fluorochrome panel for cell staining, and a standardized gating strategy, that allows the simultaneous identification and quantification of all major immune cell types in a variety of normal and inflamed non-lymphoid tissues. We demonstrate that our basic protocol minimizes cell loss, reliably distinguishes macrophages from dendritic cells (DC), and identifies all major granulocytic and mononuclear phagocytic cell types. This protocol is able to accurately quantify 11 distinct immune cell types, including T cells, B cells, NK cells, neutrophils, eosinophils, inflammatory monocytes, resident monocytes, alveolar macrophages, resident/interstitial macrophages, CD11b- DC, and CD11b+ DC, in normal lung, heart, liver, kidney, intestine, skin, eyes, and mammary gland. We also characterized the expression patterns of several commonly used myeloid and macrophage markers. This basic protocol can be expanded to identify additional cell types such as mast cells, basophils, and plasmacytoid DC, or perform detailed phenotyping of specific cell types. In examining models of primary and metastatic mammary tumors, this protocol allowed the identification of several distinct tumor associated macrophage phenotypes, the appearance of which was highly specific to individual tumor cell lines. This protocol provides a valuable tool to examine immune cell repertoires and follow immune responses in a wide variety of tissues and experimental conditions. PMID:26938654

  3. Role of ERK1/2 activation on itch sensation induced by bradykinin B1 activation in inflamed skin

    PubMed Central

    Chen, Yuanzhen; Jiang, Shuyan; Liu, Yuying; Xiong, Jialing; Liang, Jiexian; Ji, Wenjin

    2016-01-01

    It has previously been demonstrated that bradykinin receptor B1 (B1R) agonists evoke an itch-related scratching response in inflamed skin via the B1 receptor; however, the mechanisms responsible for this abnormal itch sensation remain unclear. Therefore, the present study utilized a complete Freund's adjuvant (CFA)-induced mouse model of inflammation to elucidate the mechanisms responsible. Over a period of 30 min, scratching behavior was quantified by the number of hind limb scratches of the area surrounding the drug injection site on the neck. Furthermore, western blot analysis was used to investigate the potential role of extracellular signal-regulated kinase (ERK) 1/2 signaling as a mediator of itch in CFA-treated mice. The results demonstrated that CFA-induced inflammation at the back of the neck is associated with sustained enhancement of ERK1/2 activation in the spinal cord. Moreover, B1R agonist treatment resulted in increased expression of phosphorylated ERK1/2 in the spinal cord, which peaked at 45 min. Consistent with these findings, inhibition of either mitogen-activated protein/ERK kinase or ERK1/2, as well as inhibition of ERK1/2 activation following inflammation, attenuated B1 receptor-mediated scratching responses to a greater extent, as compared with control mice. Collectively, the results of the present study indicated that enhanced and persistent ERK1/2 activation in the spinal cord may be required to induce a scratching response to B1R agonists following CFA-induced inflammation. PMID:27446253

  4. Influence of fuel injection timing and pressure on in-flame soot particles in an automotive-size diesel engine.

    PubMed

    Zhang, Renlin; Kook, Sanghoon

    2014-07-15

    The current understanding of soot particle morphology in diesel engines and their dependency on the fuel injection timing and pressure is limited to those sampled from the exhaust. In this study, a thermophoretic sampling and subsequent transmission electron microscope imaging were applied to the in-flame soot particles inside the cylinder of a working diesel engine for various fuel injection timings and pressures. The results show that the number count of soot particles per image decreases by more than 80% when the injection timing is retarded from -12 to -2 crank angle degrees after the top dead center. The late injection also results in over 90% reduction of the projection area of soot particles on the TEM image and the size of soot aggregates also become smaller. The primary particle size, however, is found to be insensitive to the variations in fuel injection timing. For injection pressure variations, both the size of primary particles and soot aggregates are found to decrease with increasing injection pressure, demonstrating the benefits of high injection velocity and momentum. Detailed analysis shows that the number count of soot particles per image increases with increasing injection pressure up to 130 MPa, primarily due to the increased small particle aggregates that are less than 40 nm in the radius of gyration. The fractal dimension shows an overall decrease with the increasing injection pressure. However, there is a case that the fractal dimension shows an unexpected increase between 100 and 130 MPa injection pressure. It is because the small aggregates with more compact and agglomerated structures outnumber the large aggregates with more stretched chain-like structures. PMID:24933154

  5. Neutrophils exposed to A. phagocytophilum under shear stress fail to fully activate, polarize, and transmigrate across inflamed endothelium.

    PubMed

    Schaff, U Y; Trott, K A; Chase, S; Tam, K; Johns, J L; Carlyon, J A; Genetos, D C; Walker, N J; Simon, S I; Borjesson, D L

    2010-07-01

    Anaplasma phagocytophilum is an obligate intracellular bacterium that has evolved mechanisms to hijack polymorphonuclear neutrophil (PMN) receptors and signaling pathways to bind, infect, and multiply within the host cell. E-selectin is upregulated during inflammation and is a requisite endothelial receptor that supports PMN capture, rolling, and activation of integrin-mediated arrest. Ligands expressed by PMN that mediate binding to endothelium via E-selectin include sialyl Lewis x (sLe(x))-expressing ligands such as P-selectin glycoprotein ligand-1 (PSGL-1) and other glycolipids and glycoproteins. As A. phagocytophilum is capable of binding to sLe(x)-expressing ligands expressed on PMN, we hypothesized that acute bacterial adhesion to PMN would subsequently attenuate PMN recruitment during inflammation. We assessed the dynamics of PMN recruitment and migration under shear flow in the presence of a wild-type strain of A. phagocytophilum and compared it with a strain of bacteria that binds to PMN independent of PSGL-1. Acute bacterial engagement with PMN resulted in transient PMN arrest and minimal PMN polarization. Although the wild-type pathogen also signaled activation of beta2 integrins and elicited a mild intracellular calcium flux, downstream signals including PMN transmigration and phosphorylation of p38 mitogen-activated protein kinase (MAPK) were inhibited. The mutant strain bound less well to PMN and failed to activate beta2 integrins and induce a calcium flux but did result in decreased PMN arrest and polarization that may have been partially mediated by a suppression of p38 MAPK activation. This model suggests that A. phagocytophilum binding to PMN under shear flow during recruitment to inflamed endothelium interferes with normal tethering via E-selectin and navigational signaling of transendothelial migration. PMID:20392928

  6. [Morphological changes in esophageal mucosa in children with overweight].

    PubMed

    Dubrovskaia, M I; Tertychnyĭ, A S; Mukhina, Iu G; Volodina, I I; Mamchenko, S I

    2010-01-01

    In present work we studied the morphological features of the esophageal mucosa in 63 children with endoscopic diagnosis of the distal esophagitis having overweight and normal weight of a body. The biopsies were taken at level of 3 cm above a Z-line and at level of 1 cm above a Z-line. Dystrophic and dysregenerative changes were revealed at the majority of children and half of children had inflammatory changes of the esophageal mucosa regardless of weight of a body. These changes are more pronounced at level of 1 cm above a Z-line, their occurrence decreases with a distance from low esophageal sphincter. We used the pathology score system for assess the esophageal biopsies. According our scale we obtained following results: at level of 1 cm above Z-lines at 95% of children had the normal, minimum or mild features of esophagitis regardless of weight of a body. Morphological evidence of a reflux esophagitis was diagnosed statistically more often at level of 1 cm above Z lines in comparison with level of 3 cm above Z-lines (p < 0.01) as among children with overweight of the body (78 and 43% accordingly), and among children with normal weight of the body (78 and 35% accordingly). The obtained data will be allowed to avoid hyperdiagnostics of esophageal lesions in children. PMID:20405708

  7. Optimum Topical Delivery of Adrenergic Agonists to Oral Mucosa Vasculature

    PubMed Central

    Soref, Cheryl M.

    2015-01-01

    Purpose Identify an orotopical vehicle to deliver an α-adrenergic vasoconstrictor to submucosal vasculature that is readily palatable to cancer/bone marrow transplant patients that suppresses chemo-radiotherapy-associated oral mucositis. Methods A [3H] norepinephrine ligand binding assay was developed to quantify receptor binding in hamster oral mucosa. Vehicle components (alcohols, polyols, cellulose, PVP) were tested versus [3H] norepinephrine binding. Vehicle refinement was also done to mask phenylephrine bitter taste and achieve human subject acceptance. The optimized vehicle was tested with α-adrenergic active agents to suppress radiation-induced oral mucositis in mice. Results The ligand binding assay quantified dose- and time-dependent, saturable binding of [3H] norepinephrine. An ethanol:glycerol:propylene glycol:water (6:6:8:80) vehicle provided the best delivery and binding. Further vehicle modification (flavoring and sucralose) yielded a vehicle with excellent taste scores in humans. Addition of phenylephrine, norepinephrine or epinephrine to the optimized vehicle and painting into mouse mouths 20 min before 19 Gy irradiation conferred significant suppression of the weight loss (P < 0.001) observed in mice who received oral vehicle. Conclusion We identified a highly efficient vehicle for the topical delivery of phenylephrine to the oral mucosa of both hamster and human subjects. This will enable its testing to suppress oral mucositis in an upcoming human clinical trial. PMID:25079392

  8. Alterations in the laryngeal mucosa after exposure to asbestos.

    PubMed Central

    Kambic, V; Radsel, Z; Gale, N

    1989-01-01

    The laryngeal mucosa of 195 workers in an asbestos cement factory (Salonit Anhovo, Yugoslavia) and in a control group was examined. The factory manufactures asbestos cement products containing about 13% of asbestos (8% amosite, 12% crocidolite, and 80% chrysotile) of different provenance. Alterations in the laryngeal mucosa were more frequent in the factory workers than in the control group. The changes, mostly consistent with chronic laryngitis, were closely related to the degree of workplace pollution and less so to the duration of employment Ten workers exhibiting the most severe clinical changes underwent biopsy, the results of which showed histomorphological changes characteristic of hyperplastic chronic laryngitis. Four tissue specimens were examined also by scanning electron microscopy and in three of them asbestos fibres were found on the epithelial surface. No case of laryngeal carcinoma was identified. On the basis of our results it is thought that asbestos related changes of the larynx should receive more attention and that the use of the term "laryngeal asbestosis" is justified. The clinical picture is non-specific but in view of their frequency such changes should be considered a consequence of exposure to asbestos. Images PMID:2489023

  9. The Length of the Barrett's Mucosa in Baboons, Revisited

    PubMed Central

    RUBIO, CARLOS A.; NILSSON, JOHN R.; OWSTON, MICHAEL; DICK, EDWARD J.

    2012-01-01

    Background Chewing of regurgitated food with rumination elicits, gastroesophageal reflux (GER) in baboons. Protracted reflux transforms the distal multilayered squamous cell-lined epithelium into columnar-lined mucosa, with mucus-producing glands having interspersed oxyntic glands. In humans, this histological constellation is called Barrett's mucosa type 2 (BMT2). Materials and Methods The distal esophagus together with the proximal stomach was removed en bloc, at autopsy, from 35 adult baboons. Longitudinal sections were stained with toluidine blue, a stain that permits easy discrimination between parietal and chief gastric glands. Using a calibrated ocular scale, the length of the BMT2 was assessed in all 35 baboons. Results The mean length of the BMT2 was 9.80 mm (range 1.0 mm–40.2 mm). Conclusion BMT2 in baboons is an integrated part of the natural phenomenon of mucosal adaptation to daily regurgitation of gastric acid into the distal esophagus (natural GER), whereas BMT2 in humans might reflect an evolutionary atavism in the esophagus, triggered by a non-physiological disorder (pathological GER). The baboon offers a suitable model to monitor the series of histological events that take place in the distal esophagus under the influence of protracted GER. PMID:22843881

  10. Preparation and characterization of a biologic scaffold from esophageal mucosa.

    PubMed

    Keane, Timothy J; Londono, Ricardo; Carey, Ryan M; Carruthers, Christopher A; Reing, Janet E; Dearth, Christopher L; D'Amore, Antonio; Medberry, Christopher J; Badylak, Stephen F

    2013-09-01

    Biologic scaffolds composed of extracellular matrix (ECM) are commonly used to facilitate a constructive remodeling response in several types of tissue, including the esophagus. Surgical manipulation of the esophagus is often complicated by stricture, but preclinical and clinical studies have shown that the use of an ECM scaffold can mitigate stricture and promote a constructive outcome after resection of full circumference esophageal mucosa. Recognizing the potential benefits of ECM derived from homologous tissue (i.e., site-specific ECM), the objective of the present study was to prepare, characterize, and assess the in-vivo remodeling properties of ECM from porcine esophageal mucosa. The developed protocol for esophageal ECM preparation is compliant with previously established criteria of decellularization and results in a scaffold that maintains important biologic components and an ultrastructure consistent with a basement membrane complex. Perivascular stem cells remained viable when seeded upon the esophageal ECM scaffold in-vitro, and the in-vivo host response showed a pattern of constructive remodeling when implanted in soft tissue. PMID:23777917

  11. Subarachnoid space of the CNS, nasal mucosa, and lymphatic system.

    PubMed

    Jackson, R T; Tigges, J; Arnold, W

    1979-04-01

    We have briefly reviewed the literature pertaining to the movement of tracer molecules and infectious organisms within the olfactory nerve. There is a body of evidence indicating that tracers placed in the CSF will quickly move via the olfactory nerve to the nasal mucosa and then to the cervical lymph nodes. Organic and inorganic tracer materials and organisms as diverse as viruses, a bacillus, and an amoeba, when placed in the nasal cavity, have been shown to move from the nasal mucosa via the olfactory nerve to the olfactory bulb and the CSF. We think that a portion of the data on tracer movement is due to incorporation of tracer materials and organisms into the axoplasm of the olfactory neurons with subsequent anterograde or retrograde axoplasmic transport. However, some of the movement of tracers may occur within the olfactory perineural space. This space may be continuous with a subarachnoid extension that surrounds the olfactory nerve as it penetrates the cribriform plate. To our knowledge, no one has yet followed the perineural space to determine if it is continuous from olfactory receptor to olfactory bulb. The consideration of this space and its role is the main reason for this review. PMID:85446

  12. Alterations in Ileal Mucosa Bacteria Related to Diet Complexity and Growth Performance in Young Pigs

    PubMed Central

    Levesque, Crystal L.; Hooda, Seema; Swanson, Kelly S.; de Lange, Kees

    2014-01-01

    Background Evaluation of the prolonged impact of weaning diet on ileal mucosa bacteria and during periods of reduced and improved growth was conducted using 454 pyrosequencing. Methodology/Principal Findings Weaned pigs were fed HIGH or LOW complexity diets, with or without antibiotics, for 6 weeks, followed by a common grower diet. Pigs were killed at 2 (n = 4 or 5) and 8 (n = 6) weeks post-weaning (periods of reduced and improved growth, respectively). Mucosal bacteria were removed; DNA was extracted and amplified using the V1–V3 region of the 16S rRNA gene. Mucosal bacteria clustered more closely by week post-weaning than diet but 44% of bacterial species did not change from week 2 to 8. There was no effect of diet complexity or antibiotic inclusion on indices of bacterial diversity. Firmicutes made up 91 and 96% of total reads at week 2 and 8, respectively. The proportion of Clostridium paraputrificum increased (P = 0.003) from week 2 to 8 in pigs fed LOW but didn’t change in pigs fed HIGH; whereas Clostridium leptum decreased (P = 0.02) from week 2 to 8 in pigs fed LOW but didn’t change in pigs fed HIGH. The proportion of Sarcina genus was 3-fold higher in pigs fed A+ compared to A− at week 2 and 5-fold higher at week 8 despite the lack of in-feed antibiotics at that time. Conclusions/Significance Shifts in mucosal bacteria populations may be related to dietary induced changes in growth performance during reduced and improved growth but further studies are required to confirm causative relationship. Weaning diet results in species specific prolonged alterations in mucosal bacteria, particularly where high levels of in-feed antibiotics are used. A considerable portion of ileal mucosal bacteria colonize early and remain stable over time despite changes in diet. PMID:25247930

  13. Multiple recurrent vesicles in oral mucosa suggestive of superficial mucocele: An unusual presentation of allergic stomatitis

    PubMed Central

    Motallebnejad, Mina; Shirzad, Atena; Molania, Tahere; Seyedmajidi, Maryam

    2013-01-01

    Background: Superficial mucocele presents as small, clear vesicle on noninflamed mucosa. In this study, we report several vesicles on the bucal mucosa of a woman diagnosed as superficial mucocele. Case Presentation: A 48-year old woman presented with multiple vesicles on her labial mucosa, ventral surface of the tongue, floor of the mouth and palate. A mucosal biopsy was taken from the vesicle. Histopathologically, intraepithelial mucocele was diagnosed. The lesion was successfully treated with mouthwash betamethasone. There has been no recurrence for 18 months. Conclusion: In the present study, several mucoceles were seen in the oral mucosa. No similar case was reported previously. PMID:24294477

  14. Engraftment and regenerative effects of bone marrow stromal cell transplantation on damaged rat olfactory mucosa.

    PubMed

    Kwon, Jang-Woo; Jo, Hyo Gyeong; Park, Sang Man; Ku, Cheol Hyo; Park, Dong-Joon

    2016-09-01

    To develop a new therapeutic method to treat olfactory deficits, we investigated the engraftment and regenerative effects of transplanted bone marrow stromal cells (BMSCs) on damaged rat olfactory mucosa. To induce olfactory nerve degeneration, one side of the olfactory mucosa of Sprague-Dawley rats was damaged via Triton X-100 irrigation. Phosphate-buffered saline containing syngeneic BMSCs was injected into the olfactory mucosa for transplantation. PKH fluorescent cell dye labeling of BMSCs was used to monitor the transplanted cells. After transplantation of BMSCs, the thickness and regeneration of olfactory mucosa were analyzed using hematoxylin-eosin (H&E) staining. S100 immunohistochemical staining was used to measure nerve sheath regeneration. The increase in NGF (nerve growth factor) level in the olfactory mucosa was measured by Western blot analysis. Transplanted bone marrow stromal cells were engrafted to the lamia propria of damaged mucosa. The mean time for normalization of thickness and morphological recovery of the olfactory mucosa was 4 weeks in the therapeutic group and 9 weeks in the control group. S100 immunoreactivity was higher on the BMSC-treated side than on the control side. During regeneration, the expression of NGF increased in the olfactory mucosa of the experimental group. Based on these results, BMSC transplantation accelerated regeneration of olfactory mucosa damaged by Triton X-100, and NGF may be essential to this regenerative process. PMID:26940801

  15. Comparative endoscopic evaluation of normal and ulcerated gastric mucosae in Thoroughbred foals

    PubMed Central

    OKAI, Kazuhiko; TAHARAGUCHI, Sadao; ORITA, Yasuhiro; YOKOTA, Hiroshi; TANIYAMA, Hiroyuki

    2015-01-01

    To contribute to early diagnosis and treatment of gastric ulcer of foals, we examined the gastric mucosa of healthy and affected foals using an endoscope. In healthy foals, the characteristic changes in the development of the squamous mucosa were seen mainly in the squamous mucosa, and maturation of the squamous mucosa in the greater curvature (GC-S) occurred more slowly than that of the squamous mucosa in the lesser curvature (LC-S). Epithelial desquamation in the LC-S and GC-S was observed between 6 and 90 days but was not observed in the LC-S at about 60 days, whereas it was observed in the GC-S until 90 days old. These findings suggest that there is a difference in the development of the gastric mucosa by region and that desquamation continues over a term longer than studies have reported in the past. In the affected foals, the minimum age at which gastric ulcer was observed was 4 days old. Gastric ulcers formed predominantly in the squamous mucosa (LC-S and GC-S) of foals with an immature mucosa before the weaning period, and the peak incidence occurred between 61 and 90 days old. The differences in the ulceration sites were considered to depend on the difference in the development (maturation) stage of the squamous mucosa. The grading score of the gastric ulcer increased with the growth of the affected foals. The gastric ulcer might be enhanced greatly by stress in the weaning period. PMID:25648790

  16. Development of enoxaparin sodium polymeric microparticles for colon-specific delivery

    PubMed Central

    HALES, DANA; CASTERAN, MAXIME; SAPIN-MINET, ANNE; TOMUŢA, IOAN; ACHIM, MARCELA; VLASE, LAURIAN; MAINCENT, PHILIPPE

    2015-01-01

    Background and aims Recent studies have shown that low molecular weight heparins are effective in the treatment of inflammatory bowel disease. Therefore, there is considerable interest in the development of an oral colonic delivery pharmaceutical system allowing targeted release of heparin in the inflamed tissue. The objective of this study was to prepare microparticles for the oral administration and colonic release of enoxaparin and to evaluate the influence of certain formulation factors on their characteristics. Methods Microparticles were prepared by water/oil/water double emulsion technique followed by solvent evaporation. The influence of several formulation factors on the characteristics of microparticles were evaluated. The formulation factors were alginate concentration in the inner aqueous phase, polymer (Eudragit® FS 30D and Eudragit® RS PO) concentration in the organic phase and ratios between the two polymers. The microparticles were characterized in terms of morphology, size, entrapment efficiency and enoxaparin release. Results The results showed that increasing sodium alginate percentage reduced the encapsulation efficiency of enoxaparin and accelerated enoxaparin release. Regarding the influence of the two polymers, reducing polymer concentration in the organic phase led to a smaller size of microparticles, a lower entrapment efficiency and an important retardation of enoxaparin release. The formulation prepared with Eudragit® FS 30D limited the release to a maximum of 3% in gastric simulated enviro