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Sample records for attenuates experimental colitis

  1. Etanercept attenuates TNBS-induced experimental colitis: role of TNF-α expression.

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    Paiotti, Ana Paula Ribeiro; Miszputen, Sender Jankiel; Oshima, Celina Tizuko Fujiyama; Artigiani Neto, Ricardo; Ribeiro, Daniel Araki; Franco, Marcello

    2011-10-01

    Crohn's disease (CD) is associated with gut barrier dysfunction. Tumour necrosis factor-α (TNF-α) plays an important role into the pathogenesis of several inflammatory diseases because its expression is increased in inflamed mucosa of CD patients. Anti-TNF therapy improves significantly mucosal inflammation. Thus, this study aimed to evaluate the effect of Etanercept (ETC), a tumour necrosis factor alpha (TNF-α) antagonist on the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. A total of 18 Wistar rats were randomized into four groups, as follows: (1) Sham: sham induced-colitis; (2) TNBS: non-treated induced-colitis; (3) ETC control; (4) ETC-treated induced-colitis. Rats from group 4 presented significant improvement either of macroscopic or of histopathological damage in the distal colon. The gene expression of TNF-α mRNA, decreased significantly in this group compared to the TNBS non-treated group. The treatment with etanercept attenuated the colonic damages and reduced the inflammation caused by TNBS. Taken together, our results suggest that ETC attenuates intestinal colitis induced by TNBS in Wistar rats by TNF-α downregulation.

  2. Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice

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    Pandurangan AK

    2015-07-01

    Full Text Available Ashok Kumar Pandurangan,1,2 Nooshin Mohebali,2 Mohd Esa Norhaizan,1,3 Chung Yeng Looi2 1Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Laboratory of Molecular Medicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaAbstract: Gallic acid (GA is a polyhydroxy phenolic compound that has been detected in various natural products, such as green tea, strawberries, grapes, bananas, and many other fruits. In inflammatory bowel disease, inflammation is promoted by oxidative stress. GA is a strong antioxidant; thus, we evaluated the cytoprotective and anti-inflammatory role of GA in a dextran sulfate sodium (DSS-induced mouse colitis model. Experimental acute colitis was induced in male BALB/c mice by administering 2.5% DSS in the drinking water for 7 days. The disease activity index; colon weight/length ratio; histopathological analysis; mRNA expressions of IL-21 and IL-23; and protein expression of nuclear erythroid 2-related factor 2 (Nrf2 were compared between the control and experimental mice. The colonic content of malondialdehyde and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity were examined as parameters of the redox state. We determined that GA significantly attenuated the disease activity index and colon shortening, and reduced the histopathological evidence of injury. GA also significantly (P<0.05 reduced the expressions of IL-21 and IL-23. Furthermore, GA activates/upregulates the expression of Nrf2 and its downstream targets, including UDP-GT and NQO1, in DSS-induced mice. The findings of this study demonstrate the protective effect of GA on experimental colitis, which is probably due to an antioxidant nature of GA.Keywords: IL-21, NQO1, MDA, enzymic antioxidants

  3. Schistosoma mansoni proteins attenuate gastrointestinal motility disturbances during experimental colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Nathalie; E; Ruyssers; Benedicte; Y; De; Winter; Joris; G; De; Man; Natacha; D; Ruyssers; Ann; J; Van; Gils; Alex; Loukas; Mark; S; Pearson; Joel; V; Weinstock; Paul; A; Pelckmans; Tom; G; Moreels

    2010-01-01

    AIM:To investigate the therapeutic effect of Schistosoma mansoni(S.mansoni) soluble worm proteins on gastrointestinal motility disturbances during experimental colitis in mice. METHODS:Colitis was induced by intrarectal injection of trinitrobenzene sulphate(TNBS) and 6 h later,mice were treated ip with S.mansoni proteins.Experiments were performed 5 d after TNBS injection.Inflammationwas quantified using validated inflammation parameters. Gastric emptying and geometric center were measured to assess in vivo...

  4. CXCR4 antagonist AMD3100 attenuates colonic damage in mice with experimental colitis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the effects of the chemokine stromal cell-derived factor-1(CXCL12) receptor(CXCR4) antagonist AMD3100 on colonic inflammation and epithelial barrier in dextran sulfate sodium(DSS)-induced colitis in mice.METHODS:Experimental colitis was induced by administration of 5% DSS for 7 d,and assays performed on intestinal segments from the ileocecal valve to the anus.Colonic morphology was examined by hematoxylin and eosin staining.Colonic cytokines were determined by enzyme-linked immunosorbent ...

  5. Eubacterium limosum ameliorates experimental colitis and metabolite of microbe attenuates colonic inflammatory action with increase of mucosal integrity

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    Osamu Kanauchi; Masanobu Fukuda; Yoshiaki Matsumoto; Shino Ishii; Toyokazu Ozawa; Makiko Shimizu; Keiichi Mitsuyama; Akira Andoh

    2006-01-01

    AIM: To examine the effect of Eubacterium limosum (E.limosum) on colonic epithelial cell line in vitro, and to evaluate the effect of E.limosum on experimental colitis.METHODS: E.limosum was inoculated anaerobically and its metabolites were obtained. The growth stimulatory effect of the E.limosum metabolites on T84 cells was evaluated by SUDH activity, and the anti-inflammatory effect by IL-6 production. The change in mRNA of toll like receptor 4 (TLR4) was evaluated by real time PCR.Colitis was induced by feeding BALB/C mice with 2.0%dextran sodium sulfate. These mice received either 5%lyophilized E.limosum (n = 7) or control diet (n = 7).Seven days after colitis induction, clinical and histological scores, colon length, and cecal organic acid levels were determined.RESULTS: The E.limosum produced butyrate, acetate,propionate, and lactate at 0.25, 1.0, 0.025 and 0.07mmol/L, respectively in medium. At this concentration,each acid had no growth stimulating activity on T84cells; however, when these acids were mixed together at the above levels, it showed significantly high activity than control. Except for lactate, these acids significantly attenuated IL-6 production at just 0.1mmol/L. In addition, under TNF-α stimulation, butyrate attenuated the production of TLR4 mRNA. The treatment with E.limosum significantly attenuated clinical and histological scores of colitis with an increase of cecal butyrate levels, compared with the control group.CONCLUSION: E.limosum can ameliorate experimental colonic inflammation. In part, the metabolite of E.limosum, butyrate, increases mucosal integrity and shows anti-inflammatory action modulation of mucosal defense system via TLR4.

  6. Experimental colitis in mice is attenuated by topical administration of chlorogenic acid.

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    Zatorski, Hubert; Sałaga, Maciej; Zielińska, Marta; Piechota-Polańczyk, Aleksandra; Owczarek, Katarzyna; Kordek, Radzisław; Lewandowska, Urszula; Chen, Chunqiu; Fichna, Jakub

    2015-06-01

    Epidemiological data suggest that the consumption of polyphenol-rich foods reduces the incidence of cancer, coronary heart disease, and inflammation. Chlorogenic acid (CGA), an ester of caffeic and quinic acids, is one of the most abundant polyphenol compounds in human diet with proven biological effectiveness both in vitro and in vivo. The aim of the study is to investigate the possible anti-inflammatory effect of CGA in the gastrointestinal (GI) tract and its mechanism of action. We used a well-established model of colitis, induced by intracolonic (i.c.) administration of trinitrobenzenesulfonic acid (TNBS) in mice. The anti-inflammatory effect of CGA in the colon was evaluated based on the clinical and macroscopic and microscopic parameters. To investigate the mechanism of protective action of CGA, myeloperoxidase (MPO), H2O2, and NF-κB levels were assessed in the colon tissue. CGA administered i.c. at the dose of 20 mg/kg (two times daily) protected against TNBS-induced colitis more effectively than the same dose administered orally (p.o.), as evidenced by significantly lower macroscopic and ulcer scores. Furthermore, CGA (20 mg/kg, i.c.) reduced neutrophil infiltration, as demonstrated by decreased MPO activity. Moreover, CGA suppressed activation of NF-κB, as evidenced by lower levels of phospho-NF-κB/NF-κB ratio in the tissue. CGA did not affect the oxidative stress pathways. CGA exhibits anti-inflammatory properties through reduction of neutrophil infiltration and inhibition of NF-κB-dependent pathways. Our results suggest that CGA may have the potential to become a valuable supplement in the treatment of GI diseases.

  7. Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells Protect against Experimental Colitis via Attenuating Colon Inflammation, Oxidative Stress and Apoptosis.

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    Jia Yang

    Full Text Available The administration of bone mesenchymal stem cells (BMSCs could reverse experimental colitis, and the predominant mechanism in tissue repair seems to be related to their paracrine activity. BMSCs derived extracellular vesicles (BMSC-EVs, including mcirovesicles and exosomes, containing diverse proteins, mRNAs and micro-RNAs, mediating various biological functions, might be a main paracrine mechanism for stem cell to injured cell communication. We aimed to investigate the potential alleviating effects of BMSC-EVs in 2,4,6-trinitrobenzene sulfonic acid (TNBS-induced colitis model. Intravenous injection of BMSC-EVs attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI and histological colonic damage. In inflammation response, the BMSC-EVs treatment significantly reduced both the mRNA and protein levels of nuclear factor kappaBp65 (NF-κBp65, tumor necrosis factor-alpha (TNF-α, induciblenitric oxidesynthase (iNOS and cyclooxygenase-2 (COX-2 in injured colon. Additionally, the BMSC-EVs injection resulted in a markedly decrease in interleukin-1β (IL-1β and an increase in interleukin-10 (IL-10 expression. Therapeutic effect of BMSC-EVs associated with suppression of oxidative perturbations was manifested by a decrease in the activity of myeloperoxidase (MPO and Malondialdehyde (MDA, as well as an increase in superoxide dismutase (SOD and glutathione (GSH. BMSC-EVs also suppressed the apoptosis via reducing the cleavage of caspase-3, caspase-8 and caspase-9 in colitis rats. Data obtained indicated that the beneficial effects of BMSC-EVs were due to the down regulation of pro-inflammatory cytokines levels, inhibition of NF-κBp65 signal transduction pathways, modulation of anti-oxidant/ oxidant balance, and moderation of the occurrence of apoptosis.

  8. Black tea extract prevents lipopolysaccharide-induced NF-κB signaling and attenuates dextran sulfate sodium-induced experimental colitis

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    Cho Sung-Bum

    2011-10-01

    Full Text Available Abstract Background Black tea has been shown to elicit anti-oxidant, anti-carcinogenic, anti-inflammatory and anti-mutagenic properties. In this study, we investigated the impact of black tea extract (BTE on lipopolysaccharide (LPS-induced NF-κB signaling in bone marrow derived-macrophages (BMM and determined the therapeutic efficacy of this extract on colon inflammation. Methods The effect of BTE on LPS-induced NF-κB signaling and pro-inflammatory gene expression was evaluated by RT-PCR, Western blotting, immunofluorescence and electrophoretic mobility shift assay (EMSA. The in vivo efficacy of BTE was assessed in mice with 3% dextran sulfate sodium (DSS-induced colitis. The severity of colitis was measured by weight loss, colon length and histologic scores. Results LPS-induced IL-12p40, IL-23p19, IL-6 and IL-1β mRNA expressions were inhibited by BTE. LPS-induced IκBα phosphorylation/degradation and nuclear translocation of NF-κB/p65 were blocked by BTE. BTE treatment blocked LPS-induced DNA-binding activity of NF-κB. BTE-fed, DSS-exposed mice showed the less weight loss, longer colon length and lower histologic score compared to control diet-fed, DSS-exposed mice. DSS-induced IκBα phosphorylation/degradation and phosphorylation of NF-κB/p65 were blocked by BTE. An increase of cleaved caspase-3 and poly (ADP-ribose polymerase (PARP in DSS-exposed mice was blocked by BTE. Conclusions These results indicate that BTE attenuates colon inflammation through the blockage of NF-κB signaling and apoptosis in DSS-induced experimental colitis model.

  9. Grim19 Attenuates DSS Induced Colitis in an Animal Model.

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    Kim, Jae-Kyung; Lee, Seung Hoon; Lee, Seon-Young; Kim, Eun-Kyung; Kwon, Jeong-Eun; Seo, Hyeon-Beom; Lee, Han Hee; Lee, Bo-In; Park, Sung-Hwan; Cho, Mi-La

    2016-01-01

    DSS induced colitis is a chronic inflammatory disease characterized by inflammation in the gastrointestinal tract, which destabilizes the gut and induces an uncontrolled immune response. Although DSS induced colitis is generally thought to develop as a result of an abnormally active intestinal immune system, its pathogenesis remains unclear. Gene associated with retinoid interferon induced mortality (Grim) 19 is an endogenous specific inhibitor of STAT3, which regulates the expression of proinflammatory cytokines. In this study, we investigated the influence of GRIM19 in a DSS induced colitis mouse model. We hypothesized that Grim19 would ameliorate DSS induced colitis by altering STAT3 activity and intestinal inflammation. Grim19 ameliorated DSS induced colitis severity and protected intestinal tissue. The expression of STAT3 and proinflammatory cytokines such as IL-1β and TNF-α in colon and lymph nodes was decreased significantly by Grim19. Moreover, DSS induced colitis progression in a Grim19 transgenic mouse line was inhibited in association with a reduction in STAT3 and IL-17 expression. These results suggest that Grim19 attenuates DSS induced colitis by suppressing the excessive inflammatory response mediated by STAT3 activation.

  10. Agaricus bisporus attenuates dextran sulfate sodium-induced colitis.

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    Um, Min Young; Park, Jae Ho; Gwon, So Young; Ahn, Jiyun; Jung, Chang Hwa; Ha, Tae Youl

    2014-12-01

    Agaricus bisporus (white button mushroom, WBM) is widely consumed in most countries and is reported to have anti-inflammatory and antioxidant activities. However, little is known regarding its effects in dextran sulfate sodium (DSS)-induced colitis, which are related to dysfunction of intestinal immunity. The aim of the present study was to investigate the effects of WBMs in an animal model of DSS-induced colitis. Male, 4-week-old ICR mice (n=10 per group) were fed a normal diet with or without 10% WBM for 4 weeks, and colitis was induced by 3% DSS in drinking water for 7 days. WBMs prevented DSS-induced shortening of colon length (P=.033) and diminished diarrhea (P=.049) and gross bleeding (P=.001), resulting in a decreased disease activity index. Results of histological analysis showed that WBMs suppressed mucosal damage. In addition, WBMs attenuated the DSS-induced increase in myeloperoxidase activity (P=.012) and upregulation of proinflammatory cytokine tumor necrosis factor-α (P=.020) in the colon segment. Taken together, these findings suggest a possible role for the WBM as an immunomodulator that can prevent and/or treat ulcerative colitis.

  11. Angelica acutiloba Kitagawa Extract Attenuates DSS-Induced Murine Colitis.

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    Jang, Jong-Chan; Lee, Kang Min; Ko, Seong-Gyu

    2016-01-01

    We examined the protective effects of Angelica acutiloba Kitagawa (AAK) extract on a murine model of acute experimental colitis. Colitis was induced by 4% dextran sulfate sodium (DSS) in the drinking water of male C57BL/6 mice, for 7 consecutive days. Oral administration of AAK extract (500 mg/kg/day) significantly alleviated DSS-induced symptoms such as anorexia, weight loss, events of diarrhea or bloody stools, and colon shortening. Histological damage was also ameliorated, as evidenced by the architectural preservation and suppression of inflammatory cell infiltration in colonic samples. Treatment improved the colonic mRNA expression of different inflammatory markers: cytokines, inducible enzymes, matrix metalloproteinases, and tight junction-related proteins. In the isolated serum, IgE levels were downregulated. Collectively, these findings indicate the therapeutic potentials of AAK as an effective complementary or alternative modality for the treatment of ulcerative colitis.

  12. Protective effect of boldine in experimental colitis.

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    Gotteland, M; Jimenez, I; Brunser, O; Guzman, L; Romero, S; Cassels, B K; Speisky, H

    1997-08-01

    The cytoprotective and anti-inflammatory effects of boldine in an experimental model of acute colitis are reported. The administration of boldine to animals with colitis induced by the intrarectal administration of acetic acid, was found to protect against colonic damage as expressed by major reductions in the extent of cell death, tissue disorganization, and edema. Boldine also reduced the colonic neutrophil infiltration, as measured by the myeloperoxidase activity, but it did not significantly affect tissue lipoperoxides. Boldine was found to preserve the colonic fluid transport, a function otherwise markedly affected in the tissue of acid-treated animals. Results presented here provide experimental evidence supporting new cytoprotective and anti-inflammatory properties of boldine.

  13. Dipeptidyl peptidase expression during experimental colitis in mice

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    Yazbeck, Roger; Sulda, Melanie L; Howarth, Gordon S

    2010-01-01

    We have previously demonstrated that inhibition of dipeptidyl peptidase (DP) activity partially attenuates dextran sulfate sodium (DSS) colitis in mice. The aim of this study was to further investigate the mechanisms of this protection.......We have previously demonstrated that inhibition of dipeptidyl peptidase (DP) activity partially attenuates dextran sulfate sodium (DSS) colitis in mice. The aim of this study was to further investigate the mechanisms of this protection....

  14. Attenuation of colitis injury in rats using Garcinia cambogia extract.

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    dos Reis, Samara Bonesso; de Oliveira, Caroline Candida; Acedo, Simone Coghetto; Miranda, Daniel Duarte da Conceição; Ribeiro, Marcelo Lima; Pedrazzoli, José; Gambero, Alessandra

    2009-03-01

    Inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis are chronic enteropathies that probably result from a dysregulated mucosal immune response. These pathologies are characterized by oxidative and nitrosative stress, leukocyte infiltration and up-regulation of pro-inflammatory substances. Current IBD treatment presents limitations in both efficacy and safety that stimulated the search for new active compounds. Garcinia cambogia extract has attracted interest due to its pharmacological properties, including gastroprotective effects. In this study, the antiinflammatory activity of a garcinia extract was assessed in TNBS-induced colitis rats. The results obtained revealed that garcinia administration to colitic rats significantly improved the macroscopic damage and caused substantial reductions in increases in MPO activity, COX-2 and iNOS expression. In addition, garcinia extract treatment was able to reduce PGE(2) and IL-1beta colonic levels. These antiinflammatory actions could be related to a reduction in DNA damage in isolated colonocytes, observed with the comet assay. Finally, garcinia extract caused neither mortality nor toxicity signals after oral administration. As such, the antiinflammatory effects provided by the Garcinia cambogia extract result in an improvement of several parameters analysed in experimental colitis and could provide a source for the search for new antiinflammatory compounds useful in IBD treatment.

  15. The Rhizome Mixture of Anemarrhena asphodeloides and Coptis chinensis Attenuates Mesalazine-Resistant Colitis in Mice

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    Su-Min Lim

    2016-01-01

    Full Text Available We investigated the effect of DWac on the gut microbiota composition in mice with 2,3,6-trinitrobenzenesulfonic acid- (TNBS- induced colitis. Treatment with DWac restored TNBS-disturbed gut microbiota composition and attenuated TNBS-induced colitis. Moreover, we examined the effect of DWac in mice with mesalazine-resistant colitis (MRC. Intrarectal injection of TNBS in MRC mice caused severe colitis, as well as colon shortening, edema, and increased myeloperoxidase activity. Treatment with mesalazine (30 mg/kg did not attenuate TNBS-induced colitis in MRC mice, whereas treatment with DWac (30 mg/kg significantly attenuated TNBS-induced colitis. Moreover, treatment with the mixture of mesalazine (15 mg/kg and DWac (15 mg/kg additively attenuated colitis in MRC mice. Treatment with DWac and its mixture with mesalazine inhibited TNBS-induced activation of NF-κB and expression of M1 macrophage markers but increased TNBS-suppressed expression of M2 macrophage markers. Furthermore, these inhibited TNBS-induced T-bet, RORγt, TNF-α, and IL-17 expression but increased TNBS-suppressed Foxp3 and IL-10 expression. However, Th2 cell differentiation and GATA3 and IL-5 expression were not affected. These findings suggest that DWac can ameliorate MRC by increasing the polarization of M2 macrophage and correcting the disturbance of gut microbiota and Th1/Th17/Treg, as well as additively attenuating MRC along with mesalazine.

  16. Light-emitting diodes at 940nm attenuate colitis-induced inflammatory process in mice.

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    Belém, Mônica O; de Andrade, Giovana M M; Carlos, Thalita M; Guazelli, Carla F S; Fattori, Victor; Toginho Filho, Dari O; Dias, Ivan F L; Verri, Waldiceu A; Araújo, Eduardo J A

    2016-09-01

    Inflammatory bowel disease (IBD) presents intense inflammatory infiltrate, crypt abscesses, ulceration and even loss of function. Despite the clinical relevance of IBD, its current therapy remains poorly effective. Infrared wavelength phototherapy shows therapeutic potential on inflammation. Our goal was to evaluate whether light-emitting diodes (LED) at 940nm are capable of mitigating the colitis-induced inflammatory process in mice. Forty male Swiss mice were assigned into five groups: control; control treated with LED therapy; colitis without treatment; colitis treated with LED therapy; colitis treated with Prednisolone. Experimental colitis was induced by acetic acid 7.5% (pH2.5) rectal administration. LED therapy was performed with light characterized by wavelength of 940nm, 45nm bandwidth, intensity of 4.05J/cm(2), total power of 270mW and total dose of 64.8J for 4min in a single application. Colitis-induced intestinal transit delay was inhibited by LED therapy. Colitis caused an increase of colon dimensions (length, diameter, total area) and colon weight (edema), which were inhibited by LED therapy. LED therapy also decreased colitis-induced tissue gross lesion, myeloperoxidase activity, microscopic tissue damage score and the presence of inflammatory infiltrate in all intestinal layers. Furthermore, LED therapy inhibited colitis-induced IL-1β, TNF-α, and IL-6 production. We conclude LED therapy at 940nm inhibited experimental colitis-induced colon inflammation in mice, therefore, rendering it a promising therapeutic approach that deserves further investigation.

  17. Salmon cartilage proteoglycan suppresses mouse experimental colitis through induction of Foxp3{sup +} regulatory T cells

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    Mitsui, Toshihito [Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562 (Japan); Department of Digestive Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Sashinami, Hiroshi [Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562 (Japan); Sato, Fuyuki; Kijima, Hiroshi [Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Ishiguro, Yoh; Fukuda, Shinsaku [Department of Digestive Internal Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Yoshihara, Shuichi [Department of Glycomedicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Hakamada, Ken-Ichi [Department of Digestive Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Nakane, Akio, E-mail: a27k03n0@cc.hirosaki-u.ac.jp [Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562 (Japan)

    2010-11-12

    Research highlights: {yields} Salmon proteoglycan suppresses IL-10{sup -/-} cell transfer-induced colitis progression. {yields} Salmon proteoglycan suppresses Th1- and Th17-related factors in colitis mice. {yields} Salmon proteoglycan enhances Foxp3 expression. -- Abstract: Proteoglycans (PGs) are complex glycohydrates which are widely distributed in extracellular matrix (ECM). PGs are involved in the construction of ECM, cell proliferation and differentiation. ECM components are involved in transduction of proinflammatory responses, but it is still unknown whether PGs are involved in inflammatory response. In this study, we investigated the effect of PG extracted from salmon cartilage on the progression of experimental colitis-induced in severe combined immunodeficiency mice by cell transfer from interleukin-10 (IL-10){sup -/-} mice. IL-10{sup -/-} cell-transferred mice showed weight loss, colon shortening and histological appearance of mild colitis. Daily oral administration of PG attenuated the clinical progression of colitis in a dose-dependent manner. Colitis-induced mice showed the elevated expression of IFN-{gamma}, IL-12, TNF-{alpha}, IL-21, IL-23p19, IL-6, IL-17A and retinoic acid-related orphan receptor {gamma}t (ROR{gamma}t) in lamina propria mononuclear cells (LPMCs) and oral administration of PG suppressed the expression of these factors. Conversely, expression of Foxp3 that induces CD4{sup +}CD25{sup +} regulatory T cells in LPMCs was enhanced by PG administration. These findings suggested that salmon PG attenuated the progression of colitis due to suppression of inflammatory response by enhancement of regulatory T cell induction.

  18. Colitis

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    ... this page: //medlineplus.gov/ency/article/001125.htm Colitis To use the sharing features on this page, please enable JavaScript. Colitis is swelling (inflammation) of the large intestine (colon). ...

  19. IL-6 Mediates the Intestinal Microvascular Thrombosis Associated with Experimental Colitis.

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    Hozumi, Hideaki; Russell, Janice; Vital, Shantel; Granger, D Neil

    2016-03-01

    Inflammatory bowel diseases are associated with increased risk for thrombus formation both within the inflamed bowel and at distant sites. Although the increased propensity for distant organ thrombus development has been recapitulated in animal models of colitis and linked to interleukin-6 (IL-6), it remains unclear whether experimental colitis results in accelerated thrombus development within the inflamed bowel and whether IL-6 contributes to a local thrombogenic response. These issues related to thrombus formation within the inflamed bowel were addressed in mice with dextran sodium sulfate-induced colitis. Wild-type (WT) mice, IL-6 deficient (IL-6(-/-)) mice, and bone marrow chimeras (WT→WT and IL-6(-/-)→WT) were used. The effects of treatment with either an IL-6-blocking, IL-6Rα-blocking or gp130-blocking antibody were also evaluated. Disease activity index and colonic weight-to-length ratio (W/L) were used to monitor the development of colitis. Intravital videomicroscopy was used to study thrombus development (induced with the light/dye method) in mucosal vessels of the ascending colon. Thrombus development was significantly enhanced in WT colitic mice. Neither genetic deficiency nor immunoblockade of IL-6 significantly altered the disease activity index and W/L responses to dextran sodium sulfate treatment. However, colitis-induced thrombogenesis was attenuated in IL-6(-/-) mice and in WT mice treated with either the IL-6-blocking, IL-6Rα-blocking or gp130-blocking antibody. IL-6(-/-)→WT, but not WT→WT chimeras, exhibited a blunted thrombosis response to dextran sodium sulfate. These results indicate that experimental colitis is associated with accelerated thrombus development within the inflamed colon and that IL-6, derived from bone marrow-derived blood cells, is largely responsible for this response.

  20. Exosomes released by granulocytic myeloid-derived suppressor cells attenuate DSS-induced colitis in mice.

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    Wang, Yungang; Tian, Jie; Tang, Xinyi; Rui, Ke; Tian, Xinyu; Ma, Jie; Ma, Bin; Xu, Huaxi; Lu, Liwei; Wang, Shengjun

    2016-03-29

    Myeloid-derived suppressor cells (MDSC) have been described in inflammatory bowel disease (IBD), but their role in the disease remains controversial. We sought to define the effect of granulocytic MDSC-derived exosomes (G-MDSC exo) in dextran sulphate sodium (DSS)-induced murine colitis. G-MDSC exo-treated mice showed greater resistance to colitis, as reflected by lower disease activity index, decreased inflammatory cell infiltration damage. There was a decrease in the proportion of Th1 cells and an increase in the proportion of regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) from G-MDSC exo-treated colitis mice. Moreover, lower serum levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α were detected in G-MDSC exo-treated colitis mice. Interestingly, inhibition of arginase (Arg)-1 activity in G-MDSC exo partially abrogated the spontaneous improvement of colitis. In addition, G-MDSC exo could suppress CD4+ T cell proliferation and IFN-γ secretion in vitro and inhibit the delayed-type hypersensitivity (DTH) response, and these abilities were associated with Arg-1 activity. Moreover, G-MDSC exo promoted the expansion of Tregs in vitro. Taken together, these results suggest that G-MDSC exo attenuate DSS-induced colitis through inhibiting Th1 cells proliferation and promoting Tregs expansion.

  1. Effects of ketanserin on experimental colitis in mice and macrophage function.

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    Xiao, Junhua; Shao, Limei; Shen, Jiaqing; Jiang, Weiliang; Feng, Yun; Zheng, Ping; Liu, Fei

    2016-03-01

    Ketanserin is a selective 5-hydroxytryptamine (serotonin)-2A receptor (5-HT2AR) antagonist. Studies have suggested that ketanserin exerts anti-inflammatory effects independent of the baroreflex; however, the mechanisms involved remain unclear. Thus, in the present study, we aimed to evaluate the effects of ketanserin in colitis and the possible underlying mechanisms. The expression of 5-HT2AR was assessed in the colon tissues of patients with inflammatory bowel disease (IBD) and in mice with dextran sodium sulfate (DSS)-induced colitis. The therapeutic potential of ketanserin was investigated in the mice with colitis. In the colon tissue samples from the patients with IBD, a high expression level of 5-HT2AR was observed. Treatment with ketanserin attenuated the progression of experimental colitis in the mice, as indicated by body weight assessment, colon length, histological scores and cytokine release. The colonic macrophages from the ketanserin-treated mice with colitis exhibited a decreased production of inflammatory cytokines, with M2 polarization and impaired migration. The knockdown of 5-HT2AR using siRNA partly abolished the inhibitory effects of ketanserin on the release of pro-inflammatory cytokines in bone marrow derived-macrophages (BMDMs), thus demonstrating that the inhibitory effects of ketanserin on the production of inflammatory cytokines are partly dependent on 5-HT2AR. Ketanserin also inhibited the activation of nuclear factor-κB (NF-κB) in BMDMs. In conclusion, the findings of the present study demonstrate that ketanserin alleviates colitis. Its anti-inflammatory effects may be due to the promotion of the anti-inflammatory function of macrophages through 5-HT2AR/NF-κB.

  2. Glutamine treatment attenuates endoplasmic reticulum stress and apoptosis in TNBS-induced colitis.

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    Crespo, Irene; San-Miguel, Beatriz; Prause, Carolina; Marroni, Norma; Cuevas, María J; González-Gallego, Javier; Tuñón, María J

    2012-01-01

    Endoplasmic reticulum (ER) stress and apoptotic cell death play an important role in the pathogenesis and perpetuation of inflammatory bowel disease (IBD). We aimed to explore the potential of glutamine to reduce ER stress and apoptosis in a rat model of experimental IBD. Colitis was induced in male Wistar rats by intracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Glutamine (25 mg/dL) was given by rectal route daily for 2 d or 7 d. Both oxidative stress (TBARS concentration and oxidised/reduced glutathione ratio) and ER stress markers (CHOP, BiP, calpain-1 and caspase-12 expression) increased significantly within 48 h of TNBS instillation, and glutamine attenuated the extent of the changes. Glutamine also inhibited the significant increases of ATF6, ATF4 and spliced XBP-1 mRNA levels induced by TNBS instillation. TNBS-colitis resulted in a significant increase in p53 and cytochrome c expression, and a reduced Bcl-xL expression and Bax/Bcl-2 ratio. These effects were significantly inhibited by glutamine. Treatment with the amino acid also resulted in significant decreases of caspase-9, caspase-8 and caspase-3 activities. Double immunofluorescence staining showed co-localization of CHOP and cleaved caspase-3 in colon sections. Phospho-JNK and PARP-1 expression was also significantly higher in TNBS-treated rats, and treatment with glutamine significantly decreased JNK phosphorylation and PARP-1 proteolysis. To directly address the effect of glutamine on ER stress and apoptosis in epithelial cells, the ER stress inducers brefeldin A and tunicamycin were added to Caco-2 cells that were treated with glutamine (5 mM and 10 mM). The significant enhancement in PERK, ATF6 phosphorylated IRE1, BiP and cleaved caspase-3 expression induced by brefeldin A and tunicamycin was partly prevented by glutamine. Data obtained indicated that modulation of ER stress signalling and anti-apoptotic effects contribute to protection by glutamine against damage

  3. Glutamine treatment attenuates endoplasmic reticulum stress and apoptosis in TNBS-induced colitis.

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    Irene Crespo

    Full Text Available Endoplasmic reticulum (ER stress and apoptotic cell death play an important role in the pathogenesis and perpetuation of inflammatory bowel disease (IBD. We aimed to explore the potential of glutamine to reduce ER stress and apoptosis in a rat model of experimental IBD. Colitis was induced in male Wistar rats by intracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS. Glutamine (25 mg/dL was given by rectal route daily for 2 d or 7 d. Both oxidative stress (TBARS concentration and oxidised/reduced glutathione ratio and ER stress markers (CHOP, BiP, calpain-1 and caspase-12 expression increased significantly within 48 h of TNBS instillation, and glutamine attenuated the extent of the changes. Glutamine also inhibited the significant increases of ATF6, ATF4 and spliced XBP-1 mRNA levels induced by TNBS instillation. TNBS-colitis resulted in a significant increase in p53 and cytochrome c expression, and a reduced Bcl-xL expression and Bax/Bcl-2 ratio. These effects were significantly inhibited by glutamine. Treatment with the amino acid also resulted in significant decreases of caspase-9, caspase-8 and caspase-3 activities. Double immunofluorescence staining showed co-localization of CHOP and cleaved caspase-3 in colon sections. Phospho-JNK and PARP-1 expression was also significantly higher in TNBS-treated rats, and treatment with glutamine significantly decreased JNK phosphorylation and PARP-1 proteolysis. To directly address the effect of glutamine on ER stress and apoptosis in epithelial cells, the ER stress inducers brefeldin A and tunicamycin were added to Caco-2 cells that were treated with glutamine (5 mM and 10 mM. The significant enhancement in PERK, ATF6 phosphorylated IRE1, BiP and cleaved caspase-3 expression induced by brefeldin A and tunicamycin was partly prevented by glutamine. Data obtained indicated that modulation of ER stress signalling and anti-apoptotic effects contribute to protection by glutamine

  4. Ginsenoside Rd attenuates the inflammatory response via modulating p38 and JNK signaling pathways in rats with TNBS-induced relapsing colitis.

    Science.gov (United States)

    Yang, Xiao-Lai; Guo, Tian-Kang; Wang, Yan-Hong; Huang, Yan-Hui; Liu, Xia; Wang, Xiao-Xia; Li, Wan; Zhao, Xin; Wang, Li-Ping; Yan, Shuai; Wu, Di; Wu, Yong-Jie

    2012-02-01

    In this study, we investigated the effects and the protective mechanism of ginsenoside Rd (GRd) which has been identified as one of the effective compounds from ginseng on relapsing colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. After inducing relapsing colitis in experimental rats on two occasions by intracolonic injection of TNBS, GRd (10, 20 and 40 mg/kg) was administered to experimental colitis rats for 7 days. The inflammatory degree was assessed by macroscopic score, histology and myeloperoxidase (MPO) activity. The levels of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6 were determined by ELISA. Mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by western blotting method. The results showed that GRd markedly attenuates the inflammatory response to TNBS-induced relapsing colitis, as evidenced by improved signs, increased body weight, decreased colonic weight/length ratio, reduced colonic macroscopic and microscopic damage scores, inhibited the activity of MPO, lowered proinflammatory cytokine levels and suppressed phosphorylation of p38 and JNK. The possible mechanism of protection on experimental colitis after GRd administration was that it could reduce the accumulation of leukocytes and down-regulate multiple proinflammatory cytokines through modulation of JNK and p38 activation.

  5. Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice

    Institute of Scientific and Technical Information of China (English)

    Alfredo Santana; Carlos Medina; Maria Iristina Paz-Cabrera; Federico Díaz-Gonzalez; Esther Farré; Antonio Salas; Marek W Radomski; Enrique Quintero

    2006-01-01

    AIM: To study whether matrix metalloproteinase-9(MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.METHODS: MMP-9-deficient and wild-type (wt)mice were given 5% DSS in drinking water for 5 dfollowed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases,MMP-2 and MMP-9,were measured in homogenates of colonic tissue by zymography and Western blot, whereas Tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover,intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs.Finally, colonic mucosal lesions were measured by microscopic examination.RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24±0.1 vs 21.3±6.4,P<0.05) and PMN from peripheral blood in wt (0.5±0.1 vs 10.4±0.7,P<0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5±0.5 vs 14.7±3.0, P<0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelial injury were significantly attenuated when compared with wt mice.CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modulated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.

  6. Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

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    Jing Zhang

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS-induced murine experimental colitis via expanding CD11b(+Gr-1(+ myeloid-derived suppressor cells (MDSCs. Employing DSS-induced murine experimental colitis as inflammatory animal model, we found that, compared with wild-type littermates, PTP1B-null mice demonstrated greater resistance to DSS-induced colitis, as reflected by slower weight-loss, greater survival rates and decreased PMN and macrophage infiltration into the colon. The evidence collectively also demonstrated that the resistance of PTP1B-null mice to DSS-induced colitis is based on the expansion of MDSCs. First, PTP1B-null mice exhibited a greater frequency of MDSCs in the bone marrow (BM, peripheral blood and spleen when compared with wild-type littermates. Second, PTP1B levels in BM leukocytes were significantly decreased after cells were induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a negative regulator of MDSCs. Third, the adoptive transfer of MDSCs into mice with DSS-colitis significantly attenuated colitis, which accompanies with a decreased serum IL-17 level. Finally, PTP1B deficiency increased the frequency of MDSCs from BM cells likely through enhancing the activities of signal transducer and activator of transcription 3 (STAT3 and Janus kinase 2 (JAK2. In conclusion, our study provides the first evidences that PTP1B deficiency ameliorates murine experimental colitis via expanding MDSCs.

  7. Dietary uptake of Wedelia chinensis extract attenuates dextran sulfate sodium-induced colitis in mice.

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    Yuh-Ting Huang

    Full Text Available SCOPE: Traditional medicinal herbs are increasingly used as alternative therapies in patients with inflammatory diseases. Here we evaluated the effect of Wedelia chinensis, a medicinal herb commonly used in Asia, on the prevention of dextran sulfate sodium (DSS-induced acute colitis in mice. General safety and the effect of different extraction methods on the bioactivity of W. chinensis were also explored. METHODS AND RESULTS: C57BL/6 mice were administrated hot water extract of fresh W. chinensis (WCHF orally for one week followed by drinking water containing 2% DSS for nine days. WCHF significantly attenuated the symptoms of colitis including diarrhea, rectal bleeding and loss of body weight; it also reduced the shortening of colon length and histopathological damage caused by colonic inflammation. Among four W. chinensis extracts prepared using different extraction techniques, WCHF showed the highest anti-colitis efficacy. Analyses of specific T-cell regulatory cytokines (TNF-α, IL-4, IFN-γ, IL-17, TGF-β, IL-12 revealed that WCHF treatment can suppress the Th1 and Th17, but not Th2, responses in colon tissues and dendritic cells of DSS-induced colitis mice. A 28-day subacute toxicity study showed that daily oral administration of WCHF (100, 500, 1000 mg/kg body weight was not toxic to mice. CONCLUSION: Together, our findings suggest that specific extracts of W. chinensis have nutritional potential for future development into nutraceuticals or dietary supplements for treatment of inflammatory bowel disease.

  8. Cellular localization, binding sites, and pharmacologic effects of TFF3 in experimental colitis in mice

    DEFF Research Database (Denmark)

    Kjellev, Stine; Thim, Lars; Pyke, Charles;

    2007-01-01

    -counting. The effect of systemically administered TFF3 on DSS-induced colitis was assessed. We found increased expression of endogenous TFF3 and increased binding of injected (125)I-TFF3 in the colon of animals with DSS-induced colitis. The distribution of intraperitoneally and subcutaneously administered (125)I-TFF3...... was comparable. Systemic administration of the peptides reduced the severity of colitis. Expression of endogenous TFF3 and binding of systemically administered TFF3 are increased in DSS-induced colitis. Systemic administration of TFF3 attenuates the disease. These findings suggest a role of TFF3 in mucosal...

  9. Ginseng Berry Extract Attenuates Dextran Sodium Sulfate-Induced Acute and Chronic Colitis.

    Science.gov (United States)

    Zhang, Wei; Xu, Li; Cho, Si-Young; Min, Kyung-Jin; Oda, Tatsuya; Zhang, LiJun; Yu, Qing; Jin, Jun-O

    2016-04-05

    This study investigates the in vivo functions of ginseng berry extract (GB) as a therapy for dextran sodium sulfate (DSS)-induced colitis. C57BL/6 mice were given drinking water containing DSS (3%) for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg) once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103(-)CD11c⁺ dendritic cells (cDCs), and macrophages. In addition, GB treatment promoted the migration of CD103⁺CD11c⁺ cDCs and expansion of Foxp3⁺ regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis.

  10. Vinegar Treatment Prevents the Development of Murine Experimental Colitis via Inhibition of Inflammation and Apoptosis.

    Science.gov (United States)

    Shen, Fengge; Feng, Jiaxuan; Wang, Xinhui; Qi, Zhimin; Shi, Xiaochen; An, Yanan; Zhang, Qiaoli; Wang, Chao; Liu, Mingyuan; Liu, Bo; Yu, Lu

    2016-02-10

    This study investigated the preventive effects of vinegar and acetic acid (the active component of vinegar) on ulcerative colitis (UC) in mice. Vinegar (5% v/v) or acetic acid (0.3% w/v) treatment significantly reduced the disease activity index and histopathological scores, attenuated body weight loss, and shortened the colon length in a murine experimental colitis model induced by dextran sulfate sodium (DSS). Further mechanistic analysis showed that vinegar inhibited inflammation through suppressing Th1 and Th17 responses, the NLRP3 inflammasome, and MAPK signaling activation. Vinegar also inhibited endoplasmic reticulum (ER) stress-mediated apoptosis in the colitis mouse model. Surprisingly, pretreatment with vinegar for 28 days before DSS induction increased levels of the commensal lactic acid-producing or acetic acid-producing bacteria, including Lactobacillus, Bifidobacteria, and Enterococcus faecalis, whereas decreased Escherichia coli levels were found in the feces of mice. These results suggest that vinegar supplementation might provide a new dietary strategy for the prevention of UC.

  11. DHA protects against experimental colitis in IL-10-deficient mice associated with the modulation of intestinal epithelial barrier function.

    Science.gov (United States)

    Zhao, Jie; Shi, Peiliang; Sun, Ye; Sun, Jing; Dong, Jian-Ning; Wang, Hong-Gang; Zuo, Lu-Gen; Gong, Jian-Feng; Li, Yi; Gu, Li-Li; Li, Ning; Li, Jie-Shou; Zhu, Wei-Ming

    2015-07-01

    A defect in the intestinal barrier is one of the characteristics of Crohn's disease (CD). The tight junction (TJ) changes and death of epithelial cells caused by intestinal inflammation play an important role in the development of CD. DHA, a long-chain PUFA, has been shown to be helpful in treating inflammatory bowel disease in experimental models by inhibiting the NF-κB pathway. The present study aimed at investigating the specific effect of DHA on the intestinal barrier function in IL-10-deficient mice. IL-10-deficient mice (IL-10(-/-)) at 16 weeks of age with established colitis were treated with DHA (i.g. 35.5 mg/kg per d) for 2 weeks. The severity of their colitis, levels of pro-inflammatory cytokines, epithelial gene expression, the distributions of TJ proteins (occludin and zona occludens (ZO)-1), and epithelial apoptosis in the proximal colon were measured at the end of the experiment. DHA treatment attenuated the established colitis and was associated with reduced infiltration of inflammatory cells in the colonic mucosa, lower mean histological scores and decreased levels of pro-inflammatory cytokines (IL-17, TNF-α and interferon-γ). Moreover, enhanced barrier function was observed in the DHA-treated mice that resulted from attenuated colonic permeability, rescued expression and corrected distributions of occludin and ZO-1. The results of the present study indicate that DHA therapy may ameliorate experimental colitis in IL-10(-/-) mice by improving the intestinal epithelial barrier function.

  12. Mangiferin attenuates DSS colitis in mice: Molecular docking and in vivo approach.

    Science.gov (United States)

    Somani, Sahil; Zambad, Shitalkumar; Modi, Ketan

    2016-06-25

    Inflammation, oxidative stress and altered mucosal barrier permeability are potential etiopathological or triggering factors for inflammatory bowel disease (IBD). In this study, the therapeutic potential of Mangiferin was investigated in vivo in mouse model of colitis and also attempts were made to understand mechanistic insights of Mangiferin in IBD. In present study, colitis was induced by administration of 5% DSS for 11 days, followed by 3 days of DSS free period. On day 14, animals were sacrificed and colon tissues were taken for biochemical and histological analysis. Therapeutic treatment with Mangiferin after colitis induction (i.e. day 5) ameliorated symptoms of colitis (presence of blood in stools, body weight loss and diarrhea) as evidenced by reduced DAI score, attenuated the levels of catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO). It also decreased the colonic pro-inflammatory mediators tumor necrosis factor (TNF-α), interleukin 1β (IL-1β) levels, matrix metalloproteinase-9 (MMP-9) activity and histopathological score. Molecular docking of Mangiferin against TNF-α and MMP-9 was evaluated using GLIDE software. Mangiferin demonstrated the glide score of -8.04 kcal/mol for TNF-α and -9.97 kcal/mol for MMP-9, which indicated its binding potential with TNF-α and MMP-9. In conclusion, Mangiferin reduces colonic damage in a murine model of colitis, alleviates the oxidative and inflammatory events partly through directly influencing the activity of TNF-α and MMP-9 and therefore might have therapeutic usefulness in the management of inflammatory bowel disease.

  13. Effect of homocysteine on intestinal permeability in rats with experimental colitis, and its mechanism

    OpenAIRE

    Ding, Hao; Mei, Qiao; GAN, HUI-ZHONG; Cao, Li-Yu; Liu, Xiao-Chang; Xu, Jian-Ming

    2014-01-01

    Objective: To investigate the effect of homocysteine (Hcy) on intestinal permeability in rats with TNBS/ethanol-induced colitis and elucidate its mechanism. Methods: Sprague-Dawley rats were divided into four groups: normal, normal + Hcy injection, TNBS model, and TNBS model + Hcy injection. Experimental colitis was induced by trinitrobenzene sulfonic acid (TNBS) in 50% ethanol; rats were injected subcutaneously with Hcy from the first day after the induction of experimental colitis on 30 con...

  14. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10{sup −/−} mice by attenuating the activation of T cells and promoting their apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Udai P.; Singh, Narendra P. [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States); Singh, Balwan [National Primate Research Center, Emory University, Atlanta GA 30329 (United States); Price, Robert L. [Department of Cell and Developmental Biology, University of South Carolina, Columbia, SC 29208 (United States); Nagarkatti, Mitzi [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States); Nagarkatti, Prakash S., E-mail: Prakash.Nagarkatti@uscmed.sc.edu [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States)

    2012-01-15

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptor induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10{sup −/−} mice. JWH-133 effectively attenuated the overall clinical score, and reversed colitis-associated pathogenesis and decrease in body weight in IL-10{sup −/−} mice. After JWH-133 treatment, the percentage of CD4{sup +} T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells declined in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN) of mice with chronic colitis. JWH-133 was also effective in ameliorating dextran sodium sulfate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodo-pravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates its effect through CB2 receptors, and ameliorates chronic colitis by inducing apoptosis in activated T cells, reducing the numbers of activated T cells, and suppressing induction of mast cells, NK cells, and neutrophils at sites of inflammation in the LP. These results support the idea that the CB2 receptor agonists may serve as a therapeutic modality against IBD. -- Highlights: ► JWH-133, a cannnabinoid receptor-2 agonist ameliorates experimental colitis. ► JWH-133 suppressed inflammation and

  15. Carbon Monoxide Attenuates Dextran Sulfate Sodium-Induced Colitis via Inhibition of GSK-3β Signaling

    Directory of Open Access Journals (Sweden)

    Md. Jamal Uddin

    2013-01-01

    Full Text Available Endogenous carbon monoxide (CO is produced by heme oxygenase-1 (HO-1 which mediates the degradation of heme into CO, iron, and biliverdin. Also, CO ameliorates the human inflammatory bowel diseases and ulcerative colitis. However, the mechanism for the effect of CO on the inflammatory bowel disease has not yet been known. In this study, we showed that CO significantly increases survival percentage, body weight, colon length as well as histologic parameters in DSS-treated mice. In addition, CO inhalation significantly decreased DSS induced pro-inflammatory cytokines by inhibition of GSK-3β in mice model. To support the in vivo observation, TNF-α, iNOS and IL-10 after CO and LiCl treatment were measured in mesenteric lymph node cells (MLNs and bone marrow-derived macrophages (BMMs from DSS treated mice. In addition, we determined that CO potentially inhibited GSK-3β activation and decreased TNF-α and iNOS expression by inhibition of NF-κB activation in LPS-stimulated U937 and MLN cells pretreated with CO. Together, our findings indicate that CO attenuates DSS-induced colitis via inhibition of GSK-3β signaling in vitro and in vivo. Importantly, this is the first report that investigated the molecular mechanisms mediated the novel effects of CO via inhibition GSK-3β in DSS-induced colitis model.

  16. Bifidobacterium breve attenuates murine dextran sodium sulfate-induced colitis and increases regulatory T cell responses.

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    Bin Zheng

    Full Text Available While some probiotics have shown beneficial effects on preventing or treating colitis development, others have shown no effects. In this study, we have assessed the immunomodulating effects of two probiotic strains, Lactobacillus rhamnosus (L. rhamnosus and Bifidobacterium breve (B. breve on T cell polarization in vitro, using human peripheral blood mononuclear cells (PBMC, and in vivo, using murine dextran sodium sulfate (DSS colitis model. With respect to the latter, the mRNA expression of T cell subset-associated transcription factors and cytokines in the colon was measured and the T helper type (Th 17 and regulatory T cell (Treg subsets were determined in the Peyer's patches. Both L. rhamnosus and B. breve incubations in vitro reduced Th17 and increased Th2 cell subsets in human PBMCs. In addition, B. breve incubation was also able to reduce Th1 and increase Treg cell subsets in contrast to L. rhamnosus. In vivo intervention with B. breve, but not L. rhamnosus, significantly attenuated the severity of DSS-induced colitis. In DSS-treated C57BL/6 mice, intervention with B. breve increased the expression of mRNA encoding for Th2- and Treg-associated cytokines in the distal colon. In addition, intervention with B. breve led to increases of Treg and decreases of Th17 cell subsets in Peyer's patches of DSS-treated mice. B. breve modulates T cell polarization towards Th2 and Treg cell-associated responses in vitro and in vivo. In vivo B. breve intervention ameliorates DSS-induced colitis symptoms and this protective effect may mediated by its effects on the T-cell composition.

  17. Baicalin attenuates TNBS-induced colitis in rats by modulating the Th17/Treg paradigm.

    Science.gov (United States)

    Zou, Ying; Dai, Shi-Xue; Chi, Hong-Gang; Li, Tao; He, Zhi-Wei; Wang, Jian; Ye, Cai-Guo; Huang, Guo-Liang; Zhao, Bing; Li, Wen-Yang; Wan, Zheng; Feng, Jin-Shan; Zheng, Xue-Bao

    2015-10-01

    Baicalin, a flavonoid, has a wide range of pharmacological properties, including immunomodulation. The objective of this study was to investigate the effect of baicalin on the balance of T helper 17 (Th17) and regulatory T (Treg) cells in a colitis model. The rat colitis model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baicalin (10 ml/kg, each) or mesalazine (positive control) was then administered orally for 7 days. Inflammatory and immunological responses were evaluated by pathology, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blot analysis, and flow cytometry. Our study showed that baicalin not only significantly attenuated TNBS-induced colitis by reducing the disease activity index as well as macroscopic and microscopic scores, but it also improved the weight loss and shortening of the colon. Baicalin treatment also induced a significant decrease in the levels of inflammatory mediators, including the myeloperoxidase activity, the levels of tumor necrosis factor α, IL-1β, and Th1-related cytokines IL-12 and IFN-γ. Furthermore, the beneficial effects of baicalin seem to be associated with regulation of the Th17 and Treg paradigm. We found that administration of baicalin significantly downregulated the number of Th17 cells and the levels of Th17-related cytokines (IL-17 and IL-6) and retinoic acid receptor-related orphan receptor γt. In contrast, there was an increase in Treg cells numbers, Treg-related cytokines transforming growth factor-β and IL-10, and forkhead box P3. Our results suggest that the anti-inflammatory effect of baicalin may be linked to modulation of the balance between Th17 and Treg cells in TNBS-induced ulcerative colitis.

  18. Pglyrp-Regulated Gut Microflora Prevotella falsenii, Parabacteroides distasonis and Bacteroides eggerthii Enhance and Alistipes finegoldii Attenuates Colitis in Mice.

    Science.gov (United States)

    Dziarski, Roman; Park, Shin Yong; Kashyap, Des Raj; Dowd, Scot E; Gupta, Dipika

    2016-01-01

    Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they are regulated. Peptidoglycan recognition proteins (Pglyrps) are antibacterial, participate in maintaining intestinal microflora, and modulate inflammatory responses. Mice deficient in any one of the four Pglyrp genes are more sensitive to dextran sulfate sodium (DSS)-induced colitis, and stools from Pglyrp-deficient mice transferred to wild type (WT) germ-free mice predispose them to much more severe colitis than stools from WT mice. However, the identities of these Pglyrp-regulated bacteria that predispose Pglyrp-deficient mice to colitis or protect WT mice from colitis are not known. Here we identified significant changes in β-diversity of stool bacteria in Pglyrp-deficient mice compared with WT mice. The most consistent changes in microbiome in all Pglyrp-deficient mice were in Bacteroidales, from which we selected four species, two with increased abundance (Prevotella falsenii and Parabacteroides distasonis) and two with decreased abundance (Bacteroides eggerthii and Alistipes finegoldii). We then gavaged WT mice with stock type strains of these species to test the hypothesis that they predispose to or protect from DSS-induced colitis. P. falsenii, P. distasonis, and B. eggerthii all enhanced DSS-induced colitis in both WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora. By contrast, A. finegoldii (which is the most abundant species in WT mice) attenuated DSS-induced colitis both in WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora, similar to the colitis protective effect of the entire normal microflora. These results identify P. falsenii, P. distasonis, and B. eggerthii as colitis-promoting species and A. finegoldii as colitis-protective species.

  19. IL-33 promotes GATA-3 polarization of gut-derived T cells in experimental and ulcerative colitis

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Coskun, Mehmet; Kvist, Peter Helding;

    2015-01-01

    of the immune response in experimental colitis (piroxicam-accelerated colitis (PAC) in IL-10 -/- mice, dextran sodium sulfate (DSS) model) and UC.METHODS: Colonic IL-33 expression was determined in UC (8 active UC, 8 quiescent UC, and 7 controls) and experimental colitis. Mesenteric lymph node (MesLN) T cells...

  20. Bifidobacterium lactis attenuates onset of inflammation in a murine model of colitis

    Institute of Scientific and Technical Information of China (English)

    David Philippe; Stéphanie Blum; Laurent Favre; Francis Foata; Oskar Adolfsson; Genevieve Perruisseau-Carrier; Karine Vidal; Gloria Reuteler; Johanna Dayer-Schneider; Christoph Mueller

    2011-01-01

    AIM: To assess the anti-inflammatory effect of the probiotic Bifidobacterium lactis (B. lactis ) in an adoptive transfer model of colitis. METHODS: Donor and recipient mice received either B. lactis or bacterial culture medium as control (deMan Rogosa Sharpe) in drinking water for one week prior to transfer of a mix of naive and regulatory T cells until sacrifice. RESULTS: All recipient mice developed signs of colonic inflammation, but a significant reduction of weight loss was observed in B. lactis -fed recipient mice compared to control mice. Moreover, a trend toward a diminution of mucosal thickness and attenuated epithelial damage was revealed. Colonic expression of pro-inflammatory and T cell markers was significantly reduced in B. lactis - fed recipient mice compared to controls. Concomitantly, forkhead box protein 3, a marker of regulatory T cells, was significantly up-regulated by B. lactis . CONCLUSION: Daily oral administration of B. lactis was able to reduce inflammatory and T cells mediators and to promote regulatory T cells specific markers in a mouse model of colitis.

  1. Different Subsets of Enteric Bacteria Induce and Perpetuate Experimental Colitis in Rats and Mice

    OpenAIRE

    Rath, Heiko C; Schultz, Michael; Freitag, René; Dieleman, Levinus A; Li, Fengling; Linde, Hans-Jörg; Schölmerich, Jürgen; Sartor, R. Balfour

    2001-01-01

    Resident bacteria are incriminated in the pathogenesis of experimental colitis and inflammatory bowel diseases. We investigated the relative roles of various enteric bacteria populations in the induction and perpetuation of experimental colitis. HLA-B27 transgenic rats received antibiotics (ciprofloxacin, metronidazole, or vancomycin-imipenem) in drinking water or water alone in either prevention or treatment protocols. Mice were treated similarly with metronidazole or vancomycin-imipenem bef...

  2. Dietary unsaponifiable fraction from extra virgin olive oil supplementation attenuates acute ulcerative colitis in mice.

    Science.gov (United States)

    Sánchez-Fidalgo, S; Cárdeno, A; Sánchez-Hidalgo, M; Aparicio-Soto, M; Villegas, I; Rosillo, M A; de la Lastra, C Alarcón

    2013-02-14

    Extra virgin olive oil (EVOO) has demonstrated immunomodulatory and antiinflammatory properties in murine experimental ulcerative colitis (UC). In addition to its high monounsaturated fatty acid content, evidences have accumulated on the favorable properties of minor, although highly bioactive, components present in the unsaponifiable fraction (UF). The present study was designed to evaluate the effects of dietary EVOO's UF supplementation on acute UC. C57BL/6 mice were fed from weaning with sunflower oil (SD), EVOO diet and UF-enriched SD at 5% oil (SD+UF). After 30 days, mice were exposed to 3% dextran sulfate sodium (DSS) for 5 days developing acute colitis. After 4 days of DSS removal, animals were sacrificed and colons were histological and biochemically processed. Disease activity index and microscopic damage score were significantly improved in EVOO and SD+UF dietary groups versus SD group. In addition, both dietary treatments significantly induced decreases in MCP-1 and TNF-α levels, iNOS and COX-2 overexpression and p38 MAPKs activation in colon mucosa. Moreover, an upregulation of IκB expression was also observed after feeding the animals with both diets. However, no statistically differences between data from mice fed with EVOO or UF+SD diets were observed. Dietary enrichment with EVOO's UF reduces the damage in acute colitis model, alleviating the oxidative events and returning proinflammatory proteins expression to basal levels probably through p38 MAPK and NFκB signalling pathways. EVOO's UF diet might provide a basis for developing a new strategy in dietary supplementation for the prevention of UC.

  3. Anti-inflammatory efficiency of levobupivacaine in an experimental colitis model

    Institute of Scientific and Technical Information of China (English)

    Ugur; Duman; Aysun; Yilmazlar; Ersin; Ozturk; Sibel; Aker

    2010-01-01

    AIM:To investigate the efficiency of levobupivacaine in treating experimentally induced colitis in rats.METHODS:Colitis was induced by trinitrobenzene sulfonic acid and ethanol in 30 rats under general anesthesia,and 10 rats were used as a sham group.Subsequent to induction of colitis,rats were divided into three groups;budesonide group received 0.1 mg/kg budesonide,levobupivacaine group received 10 mg/kg levobupivacaine and saline group received 1 mL saline solution via rectal route for 7 d.In the sham gro...

  4. mTOR Inhibition Attenuates Dextran Sulfate Sodium-Induced Colitis by Suppressing T Cell Proliferation and Balancing TH1/TH17/Treg Profile.

    Directory of Open Access Journals (Sweden)

    Shurong Hu

    Full Text Available It has been established that mammalian target of Rapamycin (mTOR inhibitors have anti-inflammatory effects in models of experimental colitis. However, the underlying mechanism is largely unknown. In this research, we investigate the anti-inflammatory effects of AZD8055, a potent mTOR inhibitor, on T cell response in dextran sulfate sodium (DSS-induced colitis in mice, a commonly used animal model of inflammatory bowel diseases (IBD. Severity of colitis is evaluated by changing of body weight, bloody stool, fecal consistency, histology evaluation and cytokine expression. We find that AZD8055 treatment attenuates DSS-induced body weight loss, colon length shortening and pathological damage of the colon. And AZD8055 treatment decreases colonic expression of genes encoding the pro-inflammatory cytokines interferon-γ, interleukin (IL-17A, IL-1β,IL-6 and tumor necrosis factor(TNF-a and increases colonic expression of anti-inflammatory cytokines IL-10. We show that AZD8055 treatment decreases the percentages of CD4+ T cells and CD8+ T cells in spleen, lymph nodes and peripheral blood of mice. We also find that AZD8055 treatment significantly reduces the number of T helper 1(TH1 cells and TH17 cells and increases regulatory T (Treg cells in the lamina propria and mesenteric lymph nodes. Furthermore, we demonstrates that AZD8055 suppresses the proliferation of CD4+ and CD8+ T cells and the differentiation of TH1/TH17 cells and expands Treg cells in vitro. The results suggest that, in experimental colitis, AZD8055 exerts anti-inflammatory effect by regulating T helper cell polarization and proliferation.

  5. Interleukin 19 reduces inflammation in chemically induced experimental colitis.

    Science.gov (United States)

    Matsuo, Yukiko; Azuma, Yasu-Taka; Kuwamura, Mitsuru; Kuramoto, Nobuyuki; Nishiyama, Kazuhiro; Yoshida, Natsuho; Ikeda, Yoshihito; Fujimoto, Yasuyuki; Nakajima, Hidemitsu; Takeuchi, Tadayoshi

    2015-12-01

    Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. Interleukin (IL)-19, a member of the IL-10 family, functions as an anti-inflammatory cytokine. Here, we investigated the contribution of IL-19 to intestinal inflammation in a model of T cell-mediated colitis in mice. Inflammatory responses in IL-19-deficient mice were assessed using the 2,4,6-trinitrobenzene sulfonic acid (TNBS) model of acute colitis. IL-19 deficiency aggravated TNBS-induced colitis and compromised intestinal recovery in mice. Additionally, the exacerbation of TNBS-induced colonic inflammation following genetic ablation of IL-19 was accompanied by increased production of interferon-gamma, IL-12 (p40), IL-17, IL-22, and IL-33, and decreased production of IL-4. Moreover, the exacerbation of colitis following IL-19 knockout was also accompanied by increased production of CXCL1, G-CSF and CCL5. Using this model of induced colitis, our results revealed the immunopathological relevance of IL-19 as an anti-inflammatory cytokine in intestinal inflammation in mice.

  6. Orally administered extract from Prunella vulgaris attenuates spontaneous colitis in mdr1a-/-mice

    Institute of Scientific and Technical Information of China (English)

    Kelley; MK; Haarberg; Meghan; J; Wymore; Brand; Anne-Marie; C; Overstreet; Catherine; C; Hauck; Patricia; A; Murphy; Jesse; M; Hostetter; Amanda; E; Ramer-Tait; Michael; J; Wannemuehler

    2015-01-01

    AIM: To investigate the ability of a Prunella vulgaris(P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a-/- mice. METHODS: Vehicle(5% ethanol) or P. vulgaris ethanolic extract(2.4 mg/d) were administered daily by oral gavage to mdr1a-/- or wild type FVBWT mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencingweight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity. RESULTS: Administration of P. vulgaris extracts to mdr1a-/- mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a-/- mice. Oral administration of the P. vulgaris extract resulted in reduced(P < 0.05) serum levels of IL-10(4.6 ± 2 vs 19.4 ± 4), CXCL9(1319.0 ± 277 vs 3901.0 ± 858), and TNFα(9.9 ± 3 vs 14.8 ± 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1 α, Mmp10, VCAM-1, ICAM, IL-2, and TNFα in the colonic mucosa of mdr1a-/- mice compared to vehicle-treated mdr1a-/-mice. Histologically, several microscopic parameters were reduced(P < 0.05) in P. vulgaris-treated mdr1a-/-mice, as was myeloperoxidase activity in the colon(2.49 ± 0.16 vs 3.36 ± 0.06, P < 0.05). The numbers of CD4+ T cells(2031.9 ± 412.1 vs 5054.5 ± 809.5) and germinal center B cells(2749.6 ± 473.7 vs 4934.0 ± 645.9) observed in the cecal tonsils of P. vulgaris-treated mdr1a-/- were significantly reduced(P < 0.05) from vehicle-treated mdr1a-/- mice. Vehicle-treated mdr1a-/- mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or

  7. Investigation of pulmonary involvement in inflammatory bowel disease in an experimental model of colitis

    Science.gov (United States)

    Aydin, Bunyamin; Songur, Yıldıran; Songur, Necla; Aksu, Oğuzhan; Senol, Altug; Ciris, I. Metin; Sutcu, Recep

    2016-01-01

    Background/Aims: Inflammatory bowel disease (IBD) may also involve various extra-intestinal organs. Clinical studies have found asymptomatic/symptomatic pulmonary involvement in 1% to 6% of patients with IBD. The present study histopathologically investigated pulmonary involvement in an experimental model of colitis in order to demonstrate pulmonary tissue involvement in IBD and to expose potential etiological factors. It also explored the relation between inflammation and tissue concentrations of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α). Methods: The study comprised 24 male Wistar albino rats. The rats were divided into four groups of six rats each. Acute colitis was induced in two separate groups using either the dextran sulphate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) method, while the other two groups were used as controls for each model of colitis. Wallace scoring was used for macroscopic assessment of colitis, and the lungs were histopathologically examined. Concentrations of VEGF and TNF-α in pulmonary tissue were measured by the enzyme-linked immunosorbent assay method. Results: The number of animals that had alveolar hemorrhage was significantly higher in the TNBS-induced colitis and DSS-induced colitis groups compared to their own control groups (p = 0.015 and p = 0.015, respectively). VEGF and TNF-α concentrations in pulmonary tissues were significantly increased in both the TNBS colitis and DSS colitis groups compared to their own control groups (p = 0.002 and p = 0.004, respectively; and p = 0.002 and p = 0.002, respectively). Conclusions: The present study demonstrated that significant and serious histopathological changes directly associated with colitis occur in the lungs in IBD. PMID:27539446

  8. Topical application of glycyrrhizin preparation ameliorates experimentally induced colitis in rats

    Institute of Scientific and Technical Information of China (English)

    Tomohiro Kudo; Shinichi Okamura; Yajing Zhang; Takashige Masuo; Masatomo Mori

    2011-01-01

    AIM: To examine the efficacy of glycyrrhizin preparation (GL-p) in the treatment of a rat model of ulcerative colitis (UC). METHODS: Experimental colitis was induced by oral administration of dextran sodium sulfate. Rats with colitis were intrarectally administered GL-p or saline. The extent of colitis was evaluated based on body weight gain,colon wet weight,and macroscopic damage score. The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis. The effect of GL-p on myeloperoxidase (MPO) activity in the inflamed mucosa and purified enzyme was assayed. RESULTS: GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline. Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines,including interleukin (IL)-1β,IL-6,tumor necrosis factor-α,cytokine-induced neutrophil chemoattractant-2,and monocyte chemoattractant protein-1 in the inflamed mucosa. Furthermore,GL-p inhibited the oxidative activity of mucosal and purified MPO. CONCLUSION: GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.

  9. Non-Hematopoietic β-Arrestin1 Confers Protection Against Experimental Colitis.

    Science.gov (United States)

    Lee, Taehyung; Lee, Eunhee; Arrollo, David; Lucas, Peter C; Parameswaran, Narayanan

    2016-05-01

    β-Arrestins are multifunctional scaffolding proteins that modulate G protein-coupled receptor (GPCR)-dependent and -independent cell signaling pathways in various types of cells. We recently demonstrated that β-arrestin1 (β-arr1) deficiency strikingly attenuates dextran sodium sulfate (DSS)-induced colitis in mice. Since DSS-induced colitis is in part dependent on gut epithelial injury, we examined the role of β-arr1 in intestinal epithelial cells (IECs) using a colon epithelial cell line, SW480 cells. Surprisingly, we found that knockdown of β-arr1 in SW480 cells enhanced epithelial cell death via a caspase-3-dependent process. To understand the in vivo relevance and potential cell type-specific role of β-arr1 in colitis development, we generated bone marrow chimeras with β-arr1 deficiency in either the hematopoietic or non-hematopoietic compartment. Reconstituted chimeric mice were then subjected to DSS-induced colitis. Similar to our previous findings, β-arr1 deficiency in the hematopoietic compartment protected mice from DSS-induced colitis. However, consistent with the role of β-arr1 in epithelial apoptosis in vitro, non-hematopoietic β-arr1 deficiency led to an exacerbated colitis phenotype. To further understand signaling mechanisms, we examined the effect of β-arr1 on TNF-α-mediated NFκB and MAPK pathways. Our results demonstrate that β-arr1 has a critical role in modulating ERK, JNK and p38 MAPK pathways mediated by TNF-α in IECs. Together, our results show that β-arr1-dependent signaling in hematopoietic and non-hematopoietic cells differentially regulates colitis pathogenesis and further demonstrates that β-arr1 in epithelial cells inhibits TNF-α-induced cell death pathways.

  10. Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis.

    Science.gov (United States)

    He, Xuexiu; Wei, Zhengkai; Wang, Jingjing; Kou, Jinhua; Liu, Weijian; Fu, Yunhe; Yang, Zhengtao

    2016-06-20

    Alpinetin, a composition of Alpinia katsumadai Hayata, has been reported to have a number of biological properties, such as antibacterial, antitumor and other important therapeutic activities. However, the effect of alpinetin on inflammatory bowel disease (IBD) has not yet been reported. The purpose of this study was to investigate the anti-inflammatory effect and mechanism of alpinetin on dextran sulfate sodium (DSS)-induced colitis in mice. In vivo, DSS-induced mice colitis model was established by giving mice drinking water containing 5% (w/v) DSS for 7 days. Alpinetin (25, 50 and 100 mg/kg) were administered once a day by intraperitoneal injection 3 days before DSS treatment. In vitro, phorbol myristate acetate (PMA)-differentiated monocytic THP-1 macrophages were treated with alpinetin and stimulated by lipopolysaccharide (LPS). The results showed that alpinetin significantly attenuated diarrhea, colonic shortening, histological injury, myeloperoxidase (MPO) activity and the expressions of tumor necrosis factor (TNF-α) and interleukin (IL-1β) production in mice. In vitro, alpinetin markedly inhibited LPS-induced TNF-α and IL-1β production, as well as Toll-like receptor 4 (TLR4) mediated nuclear transcription factor-kappaB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, this study demonstrated that alpinetin had protective effects on DSS-induced colitis and may be a promising therapeutic reagent for colitis treatment.

  11. Differential effects of energy balance on experimentally-induced colitis

    Institute of Scientific and Technical Information of China (English)

    Sarah J McCaskey; Elizabeth A Rondini; Ingeborg M Langohr; Jenifer I Fenton

    2012-01-01

    AIM:To characterize the influence of diet-induced changes in body fat on colitis severity in SMAD3-/-mice.METHODS:SMAD3-/-mice (6-8 wk of age) were randomly assigned to receive a calorie restricted (30%of control; CR),control (CON),or high fat (HF) diet for 20 wk and were gavaged with sterile broth or with Helicobacter hepaticus (H.hepaticus) to induce colitis.Four weeks after infection,mice were sacrificed and the cecum and colons were processed for histological evaluation.RESULTS:Dietary treatment significantly influenced body composition prior to infection (P < 0.05),with CR mice having less (14% ± 2%) and HF-fed mice more body fat (32% ± 7%) compared to controls (22% ±4%).Differences in body composition were associated with alterations in plasma levels of leptin (HF > CON > CR) and adiponectin (CON > HF ≥ CR) (P < 0.05).There were no significant differences in colitis scores between CON and HF-fed mice 4 wk post-infection.Consistent with this,differences in proliferation and inflammation markers (COX-2,iNOS),and infiltrating cell types (CD3+ T lymphocytes,macrophages) were not observed.Unexpectedly,only 40% of CR mice survived infection with H.hepaticus,with mortality observed as early as 1 wk following induction of colitis.CONCLUSION:Increased adiposity does not influence colitis severity in SMAD3-/-mice.Importantly,caloric restriction negatively impacts survival following pathogen challenge,potentially due to an impaired immune response.

  12. Factor XIII Transglutaminase Supports the Resolution of Mucosal Damage in Experimental Colitis.

    Directory of Open Access Journals (Sweden)

    Christina Andersson

    Full Text Available The thrombin-activated transglutaminase factor XIII (FXIII that covalently crosslinks and stablizes provisional fibrin matrices is also thought to support endothelial and epithelial barrier function and to control inflammatory processes. Here, gene-targeted mice lacking the FXIII catalytic A subunit were employed to directly test the hypothesis that FXIII limits colonic pathologies associated with experimental colitis. Wildtype (WT and FXIII-/- mice were found to be comparable in their initial development of mucosal damage following exposure to dextran sulfate sodium (DSS challenge. However, unlike FXIII-sufficient mice, FXIII-deficient cohorts failed to efficiently resolve colonic inflammatory pathologies and mucosal damage following withdrawal of DSS. Consistent with prior evidence of ongoing coagulation factor activation and consumption in individuals with active colitis, plasma FXIII levels were markedly decreased in colitis-challenged WT mice. Treatment of colitis-challenged mice with recombinant human FXIII-A zymogen significantly mitigated weight loss, intestinal bleeding, and diarrhea, regardless of whether cohorts were FXIII-sufficient or were genetically devoid of FXIII. Similarly, both qualitative and quantitative microscopic analyses of colonic tissues revealed that exogenous FXIII improved the resolution of multiple colitis disease parameters in both FXIII-/- and WT mice. The most striking differences were seen in the resolution of mucosal ulceration, the most severe histopathological manifestation of DSS-induced colitis. These findings directly demonstrate that FXIII is a significant determinant of mucosal healing and clinical outcome following inflammatory colitis induced mucosal injury and provide a proof-of-principle that clinical interventions supporting FXIII activity may be a means to limit colitis pathology and improve resolution of mucosal damage.

  13. Factor XIII Transglutaminase Supports the Resolution of Mucosal Damage in Experimental Colitis

    Science.gov (United States)

    Andersson, Christina; Kvist, Peter H.; McElhinney, Kathryn; Baylis, Richard; Gram, Luise K.; Pelzer, Hermann; Lauritzen, Brian; Holm, Thomas L.; Hogan, Simon; Wu, David; Turpin, Brian; Miller, Whitney; Palumbo, Joseph S.

    2015-01-01

    The thrombin-activated transglutaminase factor XIII (FXIII) that covalently crosslinks and stablizes provisional fibrin matrices is also thought to support endothelial and epithelial barrier function and to control inflammatory processes. Here, gene-targeted mice lacking the FXIII catalytic A subunit were employed to directly test the hypothesis that FXIII limits colonic pathologies associated with experimental colitis. Wildtype (WT) and FXIII-/- mice were found to be comparable in their initial development of mucosal damage following exposure to dextran sulfate sodium (DSS) challenge. However, unlike FXIII-sufficient mice, FXIII-deficient cohorts failed to efficiently resolve colonic inflammatory pathologies and mucosal damage following withdrawal of DSS. Consistent with prior evidence of ongoing coagulation factor activation and consumption in individuals with active colitis, plasma FXIII levels were markedly decreased in colitis-challenged WT mice. Treatment of colitis-challenged mice with recombinant human FXIII-A zymogen significantly mitigated weight loss, intestinal bleeding, and diarrhea, regardless of whether cohorts were FXIII-sufficient or were genetically devoid of FXIII. Similarly, both qualitative and quantitative microscopic analyses of colonic tissues revealed that exogenous FXIII improved the resolution of multiple colitis disease parameters in both FXIII-/- and WT mice. The most striking differences were seen in the resolution of mucosal ulceration, the most severe histopathological manifestation of DSS-induced colitis. These findings directly demonstrate that FXIII is a significant determinant of mucosal healing and clinical outcome following inflammatory colitis induced mucosal injury and provide a proof-of-principle that clinical interventions supporting FXIII activity may be a means to limit colitis pathology and improve resolution of mucosal damage. PMID:26098308

  14. Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis.

    Science.gov (United States)

    Nighot, Prashant; Al-Sadi, Rana; Rawat, Manmeet; Guo, Shuhong; Watterson, D Martin; Ma, Thomas

    2015-12-15

    Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9(-/-) mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9(-/-) mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9(-/-) mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK(-/-) mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9(-/-) mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK.

  15. Low concentrations of human neutrophil peptide ameliorate experimental murine colitis.

    Science.gov (United States)

    Maeda, Takuro; Sakiyama, Toshio; Kanmura, Shuji; Hashimoto, Shinichi; Ibusuki, Kazunari; Tanoue, Shiroh; Komaki, Yuga; Arima, Shiho; Nasu, Yuichiro; Sasaki, Fumisato; Taguchi, Hiroki; Numata, Masatsugu; Uto, Hirofumi; Tsubouchi, Hirohito; Ido, Akio

    2016-12-01

    Human neutrophil peptides (HNPs) not only have antimicrobial properties, but also exert multiple immunomodulatory effects depending on the concentration used. We have previously demonstrated that the intraperitoneal administration of high-dose HNP-1 (100 µg/day) aggravates murine dextran sulfate sodium (DSS)-induced colitis, suggesting a potential pro-inflammatory role for HNPs at high concentrations. However, the role of low physiological concentrations of HNPs in the intestinal tract remains largely unknown. The aim of this study was to examine the effects of low concentrations of HNPs on intestinal inflammation. We first examined the effects of the mild transgenic overexpression of HNP-1 in DSS-induced colitis. HNP-1 transgenic mice have plasma HNP-1 levels similar to the physiological concentrations in human plasma. Compared to wild-type mice treated with DSS, HNP-1 transgenic mice treated with DSS had significantly lower clinical and histological scores, and lower colonic mRNA levels of pro-inflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF)-α. We then injected low-dose HNP-1 (5 µg/day) or phosphate-buffered saline (PBS) intraperitoneally into C57BL/6N and BALB/c mice administered DSS. The HNP-1-treated mice exhibited significantly milder colitis with reduced expression levels of pro-inflammatory cytokines compared with the PBS-treated mice. Finally, we examined the in vitro effects of HNP-1 on the expression of cytokines associated with macrophage activation. Low physiological concentrations of HNP-1 did not significantly affect the expression levels of IL-1β, TNF-α, IL-6 or IL-10 in colonic lamina propria mononuclear cells activated with heat-killed Escherichia coli, suggesting that the anti-inflammatory effects of HNP-1 on murine colitis may not be exerted by direct action on intestinal macrophages. Collectively, our data demonstrated a biphasic dose-dependent effect of HNP-1 on DSS-induced colitis: an

  16. Therapeutic effect of curcumin on experimental colitis mediated by inhibiting CD8+CD11c+ cells

    Science.gov (United States)

    Zhao, Hai-Mei; Han, Fei; Xu, Rong; Huang, Xiao-Ying; Cheng, Shao-Min; Huang, Min-Fang; Yue, Hai-Yang; Wang, Xin; Zou, Yong; Xu, Han-Lin; Liu, Duan-Yong

    2017-01-01

    AIM To verify whether curcumin (Cur) can treat inflammatory bowel disease by regulating CD8+CD11c+ cells. METHODS We evaluated the suppressive effect of Cur on CD8+CD11c+ cells in spleen and Peyer’s patches (PPs) in colitis induced by trinitrobenzene sulfonic acid. Mice with colitis were treated by 200 mg/kg Cur for 7 d. On day 8, the therapeutic effect of Cur was evaluated by visual assessment and histological examination, while co-stimulatory molecules of CD8+CD11c+ cells in the spleen and PPs were measured by flow cytometry. The levels of interleukin (IL)-10, interferon (IFN)-γ and transforming growth factor (TGF)-β1 in spleen and colonic mucosa were determined by ELISA. RESULTS The disease activity index, colon weight, weight index of colon and histological score of experimental colitis were obviously decreased after Cur treatment, while the body weight and colon length recovered. After treatment with Cur, CD8+CD11c+ cells were decreased in the spleen and PPs, and the expression of major histocompatibility complex II, CD205, CD40, CD40L and intercellular adhesion molecule-1 was inhibited. IL-10, IFN-γ and TGF-β1 levels were increased compared with those in mice with untreated colitis. CONCLUSION Cur can effectively treat experimental colitis, which is realized by inhibiting CD8+CD11c+ cells. PMID:28348486

  17. Effects of ulinastatin in experimental colitis induced by dextran sulfate sodium in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: Ulinastatin has been reported to be beneficial for maintenance of steroid-refractory inflammatory bowel disease (IBD), but the mechanism underlying remains uncertain. Leukocyte recruitment to inflammatory site plays an important role in the pathogenesis of IBD, analysis of leukocyte and endothelium interaction may provide new avenues for treatment of IBD. In this study, we evaluated the efficacy of Ulinastatin in dextran sulfate sodium (DSS) induced colitis rat model using intravital video microscopy. METHODS: Rats were given drinking water containing 3.5% (W/V) DSS for 10 days then 1% for 14 days. DSS induced colitis rats were treated Ulinastatin 3 000 unit*kg-1*d-1 via intraperitoneum during 1% DSS feeding. Controls received distilled water for 24 days. Body weight was determined for all groups. Colitis severity was assessed using histological scoring systems by H&E sections. Intravital microscopic techniques were used to quantitate leukocyte adhesion (LA), leukocyte emigration (LE) and venular protein leakage (VPL) in rat mesentery. RESULTS: DSS induced loss of body weight, whereas Ulinastatin-treated rat showed a significant increase in body weight. Histological analysis revealed improvement of colitis such as leukocyte infiltration, loss of goblet cells, transmural edema. DSS intake elicited increase in LA, LE, and VPL compared to control group. Ulinstatin significantly reversed the increase in LA, LE, and VPL induced by DSS. CONCLUSION: Administration of Ulinastatin effectively ameliorates experimental colitis by interfering with leukocyte recruitment, and may become a potential candidate for control of inflammation of IBD.

  18. Response to Comment on "Tissue Factor-Dependent Chemokine Production Aggravates Experimental Colitis"

    NARCIS (Netherlands)

    Queiroz, K.C.; Spek, C.A.

    2011-01-01

    In our recent work we utilized genetically modified mice to investigate the role of tissue factor (TF) in experimental colitis. We present evidence suggesting TF plays a detrimental role in this disease via signal transduction dependent KC production in colon epithelial cells, which provokes granulo

  19. Preventive therapy of experimental colitis with selected iron chelators and anti-oxidants

    Directory of Open Access Journals (Sweden)

    Mohsen Minaiyan

    2012-01-01

    Conclusions: Maltol with the highest test dose was capable to protect against experimentally induced colitis. Kojic acid and vitamin E were not effective in this animal model of colon inflammation. More detailed studies are warranted to explore the mechanisms involved in anti-colitic property of maltol and to explain ineffectiveness of kojic acid and vitamin E.

  20. Negative regulation of DSS-induced experimental colitis by PILRα.

    Science.gov (United States)

    Kishida, Kazuki; Kohyama, Masako; Kurashima, Yosuke; Kogure, Yuta; Wang, Jing; Hirayasu, Kouyuki; Suenaga, Tadahiro; Kiyono, Hiroshi; Kunisawa, Jun; Arase, Hisashi

    2015-06-01

    Inflammatory bowel disease is thought to be a complex multifactorial disease, in which an increased inflammatory response plays an important role. Paired immunoglobulin-like type 2 receptor α (PILRα), well conserved in almost all mammals, is an inhibitory receptor containing immunoreceptor tyrosine-based inhibitory motifs in the cytoplasmic domain. PILRα is mainly expressed on myeloid cells and plays an important role in the regulation of inflammation. In the present study, we investigated the function of PILRα in inflammatory bowel disease using PILRα-deficient mice. When mice were orally administered dextran sulfate sodium (DSS), colonic mucosal injury and inflammation were significantly exacerbated in DSS-treated PILRα-deficient mice compared with wild-type (WT) mice. Flow cytometric analysis revealed that neutrophil and macrophage cell numbers were higher in the colons of DSS-treated PILRα-deficient mice than in those of WT mice. Blockade of CXCR2 expressed on neutrophils using a CXCR2 inhibitor decreased the severity of colitis observed in PILRα-deficient mice. These results suggest that PILRα negatively regulates inflammatory colitis by regulating the infiltration of inflammatory cells such as neutrophils and macrophages.

  1. Therapeutic effects of four strains of probiotics on experimental colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Lin-Lin Chen; Xue-Hong Wang; Yi Cui; Guang-Hui Lian; Jie Zhang; Chun-Hui Ouyang; Fang-Gen Lu

    2009-01-01

    AIM: To investigate the therapeutic effects of four strains of probiotics ( E. feacalis, L. acidophilus,C. butyricum and B. adolescentis) on dextran sulphate sodium (DSS)-induced experimental colitis in Balb/c mice.METHODS: Eighty Balb/c mice were randomly divided into 8 groups. Weight-loss, fecal character, fecal occult blood and hematochezia were recorded daily. Disease activity index (DAI) scores were also evaluated everyday. Length of colon was measured and histological scores were evaluated on the 13th day. Myeloperoxidase (MPO) activity was detected. Interleukin-1 (IL-1) and IL-4 expression was detected by ELISA and RT-PCR.RESULTS: The four strains of probiotics relieved the inflammatory condition of DSS-induced experimental colitis in mice. Weight loss was slowed down in all probiotics-treated mice. Even weight gain was observed by the end of probiotics treatment. The DAI and histological scores of probiotics-treated mice were lower than those of mice in the control group (1.9 ± 0.2vs 8.6 ± 0.4, P < 0.05 for E. faecalis). The length of colon of probiotics-treated mice was longer than thatof mice in the control group (10.3 ± 0.34 vs 8.65 ± 0.77,P < 0.05 for E. faecalis). The four strains of probiotics decreased the MP activity and the IL-1 expression, but increased the IL-4 expression. E. faecalis had a better effect on DSS-induced experimental colitis in mice than the other three strains.CONCLUSION: The four strains of probiotics have beneficial effects on experimental colitis in mice. E. faecalis has a better effect on DSS-induced experimental colitis in mice than the other three strains. Supplement of probiotics provides a new therapy for UC.

  2. Social stress-enhanced severity of Citrobacter rodentium-induced colitis is CCL2-dependent and attenuated by probiotic Lactobacillus reuteri.

    Science.gov (United States)

    Mackos, A R; Galley, J D; Eubank, T D; Easterling, R S; Parry, N M; Fox, J G; Lyte, M; Bailey, M T

    2016-03-01

    Psychological stressors are known to affect colonic diseases but the mechanisms by which this occurs, and whether probiotics can prevent stressor effects, are not understood. Because inflammatory monocytes that traffic into the colon can exacerbate colitis, we tested whether CCL2, a chemokine involved in monocyte recruitment, was necessary for stressor-induced exacerbation of infectious colitis. Mice were exposed to a social disruption stressor that entails repeated social defeat. During stressor exposure, mice were orally challenged with Citrobacter rodentium to induce a colonic inflammatory response. Exposure to the stressor during challenge resulted in significantly higher colonic pathogen levels, translocation to the spleen, increases in colonic macrophages, and increases in inflammatory cytokines and chemokines. The stressor-enhanced severity of C. rodentium-induced colitis was not evident in CCL2(-/-) mice, indicating the effects of the stressor are CCL2-dependent. In addition, we tested whether probiotic intervention could attenuate stressor-enhanced infectious colitis by reducing monocyte/macrophage accumulation. Treating mice with probiotic Lactobacillus reuteri reduced CCL2 mRNA levels in the colon and attenuated stressor-enhanced infectious colitis. These data demonstrate that probiotic L. reuteri can prevent the exacerbating effects of stressor exposure on pathogen-induced colitis, and suggest that one mechanism by which this occurs is through downregulation of the chemokine CCL2.

  3. Effect of Mesalamine and Prednisolone on TNBS Experimental Colitis, following Various Doses of Orally Administered Iron

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    John K. Triantafillidis

    2014-01-01

    Full Text Available Background. Experimental data suggest that oral iron (I. supplementation can worsen colitis in animals. Aim. To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M. and Prednisolone (P. on the severity of TNBS colitis following orally administered I. Methods and Materials. 156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor-α (t-TNF-α and tissue malondialdehyde (t-MDA were estimated in all animal groups. Results. Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF-α levels (17.67±4.92 versus 14.58±5.71, P=0.102, although it significantly reduced the t-MDA levels (5.79±1.55 versus 3.67±1.39, P=0.000. Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF-α (16.57 ± 5.61 versus 14.65±3.88, P=0.296. However, M. significantly reduced the t-MDA levels (5.99±1.37 versus 4.04±1.41, P=0.000. Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF-α levels (17.67±4.92 versus 12.64±3

  4. Interleukin-7 receptor blockade suppresses adaptive and innate inflammatory responses in experimental colitis

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    Willis Cynthia R

    2012-10-01

    Full Text Available Abstract Background Interleukin-7 (IL-7 acts primarily on T cells to promote their differentiation, survival, and homeostasis. Under disease conditions, IL-7 mediates inflammation through several mechanisms and cell types. In humans, IL-7 and its receptor (IL-7R are increased in diseases characterized by inflammation such as atherosclerosis, rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel disease. In mice, overexpression of IL-7 results in chronic colitis, and T-cell adoptive transfer studies suggest that memory T cells expressing high amounts of IL-7R drive colitis and are maintained and expanded with IL-7. The studies presented here were undertaken to better understand the contribution of IL-7R in inflammatory bowel disease in which colitis was induced with a bacterial trigger rather than with adoptive transfer. Methods We examined the contribution of IL-7R on inflammation and disease development in two models of experimental colitis: Helicobacter bilis (Hb-induced colitis in immune-sufficient Mdr1a−/− mice and in T- and B-cell-deficient Rag2−/− mice. We used pharmacological blockade of IL-7R to understand the mechanisms involved in IL-7R-mediated inflammatory bowel disease by analyzing immune cell profiles, circulating and colon proteins, and colon gene expression. Results Treatment of mice with an anti-IL-7R antibody was effective in reducing colitis in Hb-infected Mdr1a−/− mice by reducing T-cell numbers as well as T-cell function. Down regulation of the innate immune response was also detected in Hb-infected Mdr1a−/− mice treated with an anti-IL-7R antibody. In Rag2−/− mice where colitis was triggered by Hb-infection, treatment with an anti-IL-7R antibody controlled innate inflammatory responses by reducing macrophage and dendritic cell numbers and their activity. Conclusions Results from our studies showed that inhibition of IL-7R successfully ameliorated inflammation and disease development

  5. Alterations of testosterone metabolism in microsomes from rats with experimental colitis induced by dextran sulfate sodium.

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    Huang, Yanjuan; Hu, Nan; Gao, Xuejiao; Yan, Zhixiang; Li, Sai; Jing, Wanghui; Yan, Ru

    2015-05-05

    Down-regulation of some hepatic cytochrome P450s (CYP450s) was observed in patients and animals with ulcerative colitis (UC). This study examined changes of CYP450s activities in microsomes of liver (RLMs), intestine (RIMs) and kidney (RRMs) from rats with experimental acute colitis induced by 5% dextran sulfate sodium (DSS) for 7days and those receiving DSS treatment followed by 7-d cessation through measuring 6α-(CYP1A1), 7α-(CYP2A1), 16α-(CYP2C11) and 2β-/6β-(CYP3A2) hydroxytestosterone (OHT) formed from testosterone. Both pro-(IL-1β, IL-6, TNF-α) and anti-(IL-4, IL-10) inflammatory cytokines were elevated in acute colitis, while the production of the former was enhanced and that of the latter declined by DSS withdrawal. In RLMs, the CYP2A1 activity was significantly increased at DSS stimulation and partially returned to normal level when DSS treatment was terminated. Activity of other CYP450s were decreased by acute colitis and remained after DSS withdrawal. In RRMs, formations of 6α-, 16α- and 2β-OHT significantly declined in acute colitis and DSS termination further potentiated the down-regulation, while 7α-OHT formation was suppressed at DSS stimulation and remained after DSS withdrawal. The formation of 6β-OHT only showed significant decrease after DSS withdrawal. Two metabolites (6α- and 6β-OHT) formed in RIMs and 6β-OHT formation was significantly decreased by DSS stimulation and continued after DSS treatment halted. These findings indicate that the alterations of CYP450s activities vary with organ, CYP isoforms and colitis status, which arouse cautions on efficacy and toxicity of drug therapy during disease progression.

  6. Attenuated apoptosis response to Fas-ligand in active ulcerative colitis

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    Seidelin, J.B.; Nielsen, Ole Haagen

    2008-01-01

    BACKGROUND: From mainly carcinoma cell line studies, apoptosis has been thought to play a major role in the pathogenesis of ulcerative colitis (UC). Apoptosis has been suggested to be due to a Fas ligand / Fas receptor interaction, but has never been studied in cells from patients with active UC...

  7. Lipid alterations in experimental murine colitis: role of ceramide and imipramine for matrix metalloproteinase-1 expression.

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    Jessica Bauer

    Full Text Available BACKGROUND: Dietary lipids or pharmacologic modulation of lipid metabolism are potential therapeutic strategies in inflammatory bowel disease (IBD. Therefore, we analysed alterations of bioactive lipids in experimental models of colitis and examined the functional consequence of the second messenger ceramide in inflammatory pathways leading to tissue destruction. METHODOLOGY/PRINCIPAL FINDINGS: Chronic colitis was induced by dextran-sulphate-sodium (DSS or transfer of CD4(+CD62L(+ cells into RAG1(-/--mice. Lipid content of isolated murine intestinal epithelial cells (IEC was analysed by tandem mass spectrometry. Concentrations of MMP-1 in supernatants of Caco-2-IEC and human intestinal fibroblasts from patients with ulcerative colitis were determined by ELISA. Imipramine was used for pharmacologic inhibition of acid sphingomyelinase (ASM. Ceramide increased by 71% in chronic DSS-induced colitis and by 159% in the transfer model of colitis. Lysophosphatidylcholine (LPC decreased by 22% in both models. No changes were detected for phosphatidylcholine. Generation of ceramide by exogenous SMase increased MMP-1-protein production of Caco-2-IEC up to 7-fold. Inhibition of ASM completely abolished the induction of MMP-1 by TNF or IL-1beta in Caco-2-IEC and human intestinal fibroblasts. CONCLUSIONS/SIGNIFICANCE: Mucosal inflammation leads to accumulation of ceramide and decrease of LPC in the intestinal epithelium. One aspect of ceramide generation is an increase of MMP-1. Induction of MMP-1 by TNF or IL-1beta is completely blocked by inhibition of ASM with imipramine. Therefore, inhibition of ASM may offer a treatment strategy to reduce MMP-1 expression and tissue destruction in inflammatory conditions.

  8. Favorable response to subcutaneous administration of infliximab in rats with experimental colitis

    Institute of Scientific and Technical Information of China (English)

    John K Triantafillidis; Helen Sotiriou; Apostolos E Papalois; Aikaterini Parasi; Emmanuel Anagnostakis; Stavros Burnazos; Aristofanis Gikas; Emmanuel G Merikas; Emmanuel Douzinas; Maria Karagianni

    2005-01-01

    AIM: To investigate the influence of infliximab (Remicade)on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic acid (TNBS) in rats.METHODS: Thirty-six Wistar rats were allocated into four groups (three groups of six animals each and a fourth of 12 animals). Six more healthy animals served as normal controls (Group 5). Group 1:colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7th d, all animals were killed. The colon was fixed in 10%buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) were also measured.RESULTS: Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-α in all groups of treated animals as compared withthe untreated ones was found (0.47±0.44, 1.09±0.86,0.43±0.31 vs 18.73±10.53 respectively). Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4.CONCLUSION: Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-α and MDA levels in chemical colitis in rats.Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-α than at a dose of 10 mg/kg BW.Infliximab at a dose of 5 mg/kg BW produces

  9. Protective effects of citicoline on TNBS-induced experimental colitis in rats

    OpenAIRE

    Ek, Rauf Onur; Serter, Mukadder; Ergin, Kemal; Cecen, Serpil; Unsal, Cengiz; Yildiz, Yuksel; Bilgin, Mehmet D.

    2014-01-01

    The aim of this study was to investigate the effects of citicoline on the development of colitis and antioxidant parameters in rats subjected to tribenzene sulfonic acid (TNBS)-induced colitis. Twenty four Wistar Albino female rats were divided into four subgroups (n=6) (control, colitis control, colitis + 50 mg/kg citicoline, colitis + 250 mg/kg citicoline). Colitis was induced using an enema of TNBS and ethanol; following which citicoline was administrated for 3 days and effects of citicoli...

  10. Attenuated apoptosis response to Fas-ligand in active ulcerative colitis

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole H

    2008-01-01

    From mainly carcinoma cell line studies, apoptosis has been thought to play a major role in the pathogenesis of ulcerative colitis (UC). Apoptosis has been suggested to be due to a Fas ligand / Fas receptor interaction, but has never been studied in cells from patients with active UC. The aim...... was to investigate both the spontaneous and the cell death receptor ligand-induced apoptosis in UC....

  11. Curcumin-attenuated trinitrobenzene sulphonic acid induces chronic colitis by inhibiting expression of cyclooxygenase-2

    Institute of Scientific and Technical Information of China (English)

    Hua Jiang; Chang-Sheng Deng; Ming Zhang; Jian Xia

    2006-01-01

    AIM: To explore the possible mechanisms of curcumin in rat colitis induced by trinitrobenzene sulfonic (TNBS) acid. METHODS: Rats with TNBS acid-induced colitis were treated with curcumin (30 mg/kg or 60 mg/kg per day ip). Changes of body weight and histological scores as well as survival rate were evaluated. Leukocyte infiltration was detected by myeloperoxidase (MPO)activity assay. The expression of cyclooxygenase-2(COX-2) was detected by RT-PCR and Western blot.Inflammation cytokines were determined by RT-PCR.Local concentration of prostaglandin E2 (PGE2) in colon mucosa was determined by ELISA.RESULTS: Curcumin improved survival rate and histological image, decreased the macroscopic scores and MPO activity. Also curcumin reduced the expression of COX-2 and inflammation cytokines. In addition,treatment with curcumin increased the PGE2 level.CONCLUSION: Curcumin has therapeutic effects on TNBS acid-induced colitis, the mechanisms seem to be related to COX-2 inhibition and PGE2 improvement.

  12. Therapeutic effects of Clostridium butyricum on experimental colitis induced by oxazolone in rats

    Institute of Scientific and Technical Information of China (English)

    Hai-Qiang Zhang; Tomas T Ding; Jun-Sheng Zhao; Xin Yang; Hai-Xia Zhang; Juan-Juan Zhang; Yun-Long Cui

    2009-01-01

    AIM: To evaluate the therapeutic effects of a probiotic supplement ( Clostridium butyricum, CGMCC0313) in a chemically-induced rat model of experimental colitis. METHODS: An experimental ulcerative colitis model was established by rectal injection of oxazolone into the colon of 40 Wistar rats randomly divided into four groups. The positive control group was sacrificed 3 d after colitis onset. The remaining groups were fed daily with either 2 mL of C. butyricum (2.3 ?á 1011 CFU/L), 2 mL of mesalamine (100 g/L), or 1 mL of sodium butyrate (50 mmol/L) for 21 d. The animals?ˉ body weight, behavior, and bowel movements were recorded weekly. After sacrifice, visual and microscopic observations of pathological changes of colon tissue were made, body weight and wet colon mass index were measured and recorded, and serum levels of interleukin-23 (IL-23) and TNF-α were measured using ELISA. Expression of calcitonin gene-related peptide in colon tissue was measured by RT-PCR. Finally, changes in rat intestinal microflora status were measured in all groups. RESULTS: We found that treatment with C. butyricum lowered the serum levels of both IL-23 and tumor necrosis factor-α (TNF-α) with similar or even better efficiency than that of mesalamine or sodium butyrate. The rat intestinal flora appeared to recover more quickly in the group treated with C. butyricum than in the mesalamine and sodium butyrate groups. Finally, we found that the expression level of calcitonin gene related peptide was elevated in colon tissue in the sodium butyrate treated group but not in the C. butyricum or mesalamine treated groups, indicating a sensitization of colon following sodium butyrate treatment. CONCLUSION: In our experimental colitis model, treatment with C. butyricum CGMCC0313, a probiotic supplement, is at least as efficient as treatment with mesalamine.

  13. Comparative protective effect of hawthorn berry hydroalcoholic extract, atorvastatin, and mesalamine on experimentally induced colitis in rats.

    Science.gov (United States)

    Malekinejad, Hassan; Shafie-Irannejad, Vahid; Hobbenaghi, Rahim; Tabatabaie, Seyed Hamed; Moshtaghion, Seyed-Mehdi

    2013-07-01

    The protective effect of hydroalcoholic extract of hawthorn berries (HBE) on acetic acid (AA)-induced colitis in rats was investigated. Forty-two Wistar rats were divided into seven groups, including control and test groups (n=6). The control animals received saline, and the test animals were treated with saline (sham group), mesalamine (50 mg/kg; M group), atorvastatin (20 mg/kg; A group), HBE (100 mg/kg; H group), mesalamine and HBE (HM group), or atorvastatin plus HBE (HA group), 3 days before and a week after colitis induction. Colitis was induced by administration of 1 mL AA (4%) via a polyethylene catheter intrarectally. High-performance liquid chromatography analyses showed that HBE contained 0.13% and 0.5% oleanolic acid and ursolic acid, respectively. Elevated myeloperoxidase activity and lipid peroxidation were attenuated in the HA group. The H and HM groups showed marked reductions in colitis-induced decreases in total thiol molecules and body weight. The histopathological studies revealed that HBE decreased colitis-induced edema and infiltration of neutrophils. Our data suggest the anti-inflammatory and antioxidant effects of HBE and atorvastatin protect against AA-induced colitis. The anti-inflammatory effect of HBE may be attributable to its ability to decrease myeloperoxidase activity as a biomarker of neutrophil infiltration.

  14. Pseudomembranous colitis

    Science.gov (United States)

    Antibiotic-associated colitis; Colitis - pseudomembranous; Necrotizing colitis; C difficile - pseudomembranous ... this bacteria from 1 person to another. Pseudomembranous colitis is uncommon in children, and rare in infants. ...

  15. Paraoxonase and Arylesterase Activities, Lipid Profile, and Oxidative Damage in Experimental Ischemic Colitis Model

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    Ethem Unal

    2012-01-01

    Full Text Available Objective. In the present study, since PON1 is known as an HDL-associated antioxidant enzyme that inhibits the oxidative modification of LDL and oxidative stress plays a role in the pathogenesis of mesenteric ischemia, we investigated the changes in PON1 activity and lipid profile in an experimental ischemic colitis model. Methods. Forty male Wistar albino rats were divided into two groups: the control group (N=15 and the experimental group (N=25. All animals were anesthetized with ether and ketamine anesthesia to undergo a midline laparotomy. Ischemic colitis was induced by marginal vessel ligation in the splenic flexura (devascularization process. A sham laparotomy was performed in the control group. All animals were sacrificed on the seventh postoperative day. Oxidative stress marker (malonyldialdehyde, MDA, lipid profile, and paraoxonase (PON-1 and arylesterase activities were determined. Histopathological evaluation was done under light microscopy, after sectioning and staining with hematoxyline and eosin. Statistical analysis was conducted using Student’s t-test and Mann-Whitney U test, and P0.05. Conclusions. PON1 and arylesterase play an important role in the pathophysiology of ischemic colitis.

  16. Use of butyrate or glutamine in enema solution reduces inflammation and fibrosis in experimental diversion colitis

    Institute of Scientific and Technical Information of China (English)

    Rodrigo Goulart Pacheco; Christiano Costa Esposito; Lucas CM Müller; Morgana TL Castelo-Branco; Leonardo Pereira Quintella; Vera Lucia A Chagas; Heitor Siffert P de Souza

    2012-01-01

    AIM:To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.METHODS:Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing glutamine,butyrate,or saline.Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure.Follow-up colonoscopy was performed every 4 wk for 12 wk.The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1β,tumor necrosis factor-alpha,and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay.RESULTS:Colonoscopies of the diverted segment showed mucosa with hyperemia,increased number of vessels,bleeding and mucus discharge.Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic (P < 0.02) and histological scores (P < 0.01) and restored the densities of collagen fibers in tissue (P =0.015; P =0.001),the number of goblet cells (P =0.021; P =0.029),and the rate of apoptosis within the epithelium (P =0.043; P =0.011) to normal values.The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine.CONCLUSION:The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.

  17. Increased wall thickness using ultrasonography is associated with inflammation in an animal model of experimental colitis

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    Lied GA

    2012-10-01

    Full Text Available Gülen Arslan Lied,1 Anne Marita Milde,2 Kim Nylund,1,3 Maja Mujic,1 Tore Grimstad,1,4 Trygve Hausken,1,3 Odd Helge Gilja1,31Institute of Medicine, University of Bergen, Norway; 2Department of Biological and Medical Psychology, University of Bergen, Norway; 3National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway; 4Division of Gastroenterology, Stavanger University Hospital, Stavanger, NorwayAbstract: Experimentally induced colitis is used in animals to investigate pathophysiological mechanisms in inflammatory bowel disease. When following disease course and treatment effects, it should be possible to perform repeated measurements without harming the animals. This pilot study was performed to investigate whether transabdominal ultrasound using a clinical scanner could be used on rats to demonstrate bowel inflammation in an experimental colitis model. Colitis was induced by either 5% dextran sodium sulfate (DSS in drinking water for 7 days or a single dose of intracolonic trinitrobenzene sulfonic acid (TNBS. Using ultrasonography, wall thickness of distal colon, cecum, and small bowel was recorded prior to and after DSS, and prior to, 2, and 7 days after TNBS. Blood (tumor necrosis factor [TNF]-alpha and fecal samples (HemoFEC occult blood were taken from each group on the same days as sonography. Thereafter, rats were killed and specimens for histology were taken. Wall thickness of distal colon, not of cecum or small bowel, increased significantly after 7 days of DSS, and wall thickness of both distal colon and small bowel increased on day 2 and 7 after TNBS. TNF-alpha increased after 7 days in the latter group only. There was a significant correlation between ultrasonographic measurements and combined histology score of distal colon in the DSS group. HemoFEC was also positive in accordance with sonographic and histological features. Increased intestinal wall thickness in response to both DSS- and TNBS

  18. Electroacupuntura en el tratamiento de la colitis ulcerosa experimental en ratas Sprague Dawley - Electro acupuncture in the treatment of experimental ulcerous colitis in Sprague Dawley rats

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    Molina Martínez, José L.

    2010-08-01

    Full Text Available ResumenSe realizó un estudio sobre la efectividad terapéutica de la electroacupuntura (EA en la colitis ulcerosa (CU provocada experimentalmente en ratas Sprague Dawley por administración intracolónica de una disolución de ácido acético al 4%. El experimento se realizó en 57 ratas distribuidas en tres grupos: Grupo I (control placebo, al que se administró solución salina fisiológica mediante instilación intracolónica, Grupo II (control no tratado y Grupo III (estudio, integrado ambos por animales en que se reprodujo artificialmente la colitis ulcerosa. El estudio histopatológico de muestras tomadas mediante biopsias permitió corroborar la instauración de la entidad. Los acupuntos seleccionados fueronLI-4 (Hegu y ST-36 (Zusanli y la aplicación de la EA se realizó a las 24, 48 y 72 horas posteriores a la reproducción experimental de la CU. En las condiciones del estudio se comprobó que una sesión de EA a las 24 horas posteriores a la reproducción de la entidad, posee efecto anti inflamatorio y mejora notablemente la lesión tisular, no siendo eficaz en los tratamientos realizados a las 48 y 72 horas, influyendo en ello el mecanismo de transducción. Mediante el estudio histopatológico de muestras tomadas mediante biopsias se puede evaluar el estado de la mucosa en la CU y su respuesta al tratamiento mediante EA, sin necesidad de acudir a otros procedimientos más sofisticados y costosos. Se comprobó que el modelo experimental utilizado es adecuado para estudios sobre esta afección.SummaryA study was carried out on the therapeutic effectiveness ofelectroacupuncture (EA in the ulcerous colitis (UC experimentally provoked in Sprague Dawley rats by intracolonic administration of a 4 % acetic acid dissolution. The experiment was realized in 57 rats distributed in three groups: Group I (placebo control, to which physiological saline solution was administered by intracolonic instillation, Group II (not treated control and Group

  19. MALT1 inhibitors prevent the development of DSS-induced experimental colitis in mice via inhibiting NF-κB and NLRP3 inflammasome activation.

    Science.gov (United States)

    Liu, Wen; Guo, Wenjie; Hang, Nan; Yang, Yuanyuan; Wu, Xuefeng; Shen, Yan; Cao, Jingsong; Sun, Yang; Xu, Qiang

    2016-05-24

    Mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1), a paracaspase and essential regulator for nuclear factor kB (NF-κB) activation, plays an important role in innate and adaptive immunity. Suppression of MALT1 protease activity with small molecule inhibitors showed promising efficacies in subtypes of B cell lymphoma and improvement in experimental autoimmune encephalomyelitis model. However, whether MALT1 inhibitors could ameliorate colitis remains unclear. In the present study, we examined the pharmacological effect of two specific MALT1 inhibitors MI-2 and mepazine on the dextran sulfate sodium (DSS)-induced experimental colitis in mice, followed by mechanistic analysis on NF-κB and NLRP3 inflammasome activation. Treatment with MI-2 and mepazine dose-dependently attenuated symptoms of colitis in mice, evidenced by reduction in the elevated disease activity index, the shortening of colon length as well as the histopathologic improvement. Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF, IL-1β, IL-6, IL-18, IL-17A and IFN-γ, were markedly suppressed by MALT1 inhibitors. The underlying mechanisms for the protective effect of MALT1 inhibitors in DSS-induced colitis may be attributed to its inhibition on NF-κB and NLRP3 inflammasome activation in macrophages. The in vitro study showed that MALT1 inhibitors decreased production of IL-1β/IL-18 in phorbol myristate acetate-differentiated THP-1 cells and bone marrow derived macrophage via suppressing the activation of NF-κB and NLRP3 inflammasome. Taken together, our results demonstrated that inhibition of the protease activity of MALT1 might be a viable strategy to treat inflammatory bowel disease and the NLRP3 inflammasome and NF-κB activation are critical components in MALT1 signaling cascades in this disease model.

  20. Adrenal-Derived Hormones Differentially Modulate Intestinal Immunity in Experimental Colitis

    Science.gov (United States)

    de Souza, Patrícia Reis; Basso, Paulo José; Nardini, Viviani; Silva, Angelica; Banquieri, Fernanda

    2016-01-01

    The adrenal glands are able to modulate immune responses through neuroimmunoendocrine interactions and cortisol secretion that could suppress exacerbated inflammation such as in inflammatory bowel disease (IBD). Therefore, here we evaluated the role of these glands in experimental colitis induced by 3% dextran sulfate sodium (DSS) in C57BL/6 mice subjected to adrenalectomy, with or without glucocorticoid (GC) replacement. Mice succumbed to colitis without adrenals with a higher clinical score and augmented systemic levels of IL-6 and lower LPS. Furthermore, adrenalectomy negatively modulated systemic regulatory markers. The absence of adrenals resulted in augmented tolerogenic lamina propria dendritic cells but no compensatory local production of corticosterone and decreased mucosal inflammation associated with increased IFN-γ and FasL in the intestine. To clarify the importance of GC in this scenario, GC replacement in adrenalectomized mice restored different markers to the same degree of that observed in DSS group. Finally, this is the first time that adrenal-derived hormones, especially GC, were associated with the differential local modulation of the gut infiltrate, also pointing to a relationship between adrenalectomy and the modulation of systemic regulatory markers. These findings may elucidate some neuroimmunoendocrine mechanisms that dictate colitis outcome. PMID:27403034

  1. Effects of parenteral fish oil lipid emulsions on colon morphology and cytokine expression after experimental colitis

    Directory of Open Access Journals (Sweden)

    Ricardo Garib

    2013-06-01

    Full Text Available Aim: To study the effects of different protocols of fish oil lipid emulsion (FOLE infusion on acute inflammation in a rat model of colitis. Methods: Adult male Wistar rats (n = 51 were randomized into 5 groups to receive parenteral infusion of saline (SS or soybean oil lipid emulsion (SO, as controls, and FOLE composed of: fish oil alone (FO; a mixture (9:1 v/v of SO with FO (SO/FO; or 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (SMOF. After 72 h of intravenous infusion, experimental colitis was induced with acetic acid. After 24 h, colonic samples were analyzed for histological and cytokine changes. Results: In relation SS group, macroscopic necrosis was less frequent in the FO group and histological necrosis was more frequent in the SMOF group. There was a direct and inverse relation of colon interleukin (IL-1 and IL-4 respectively, with histological necrosis. In comparison to the SS group, FO increased IL-4 and IFN-gamma and decreased TNF-alpha, SO/FO decreased TNF-alpha, and SMOF increased IL-1 and decreased IL- 4. Conclusion: In acetic acid-induced colitis, the isolate infusion of FOLE composed of fish oil alone was more advantageous in mitigating inflammation than the infusion of FOLE containing other oils, and this difference may be due the influences of their different fatty acid contents.

  2. Genetic deletion of dectin-1 does not affect the course of murine experimental colitis

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    Heinsbroek Sigrid EM

    2012-04-01

    Full Text Available Abstract Background It is believed that inflammatory bowel diseases (IBD result from an imbalance in the intestinal immune response towards the luminal microbiome. Dectin-1 is a widely expressed pattern recognition receptor that recognizes fungi and upon recognition it mediates cytokine responses and skewing of the adaptive immune system. Hence, dectin-1 may be involved in the pathogenesis of IBD. Methods We assessed the responses of dectin-1 deficient macrophages to the intestinal microbiota and determined the course of acute DSS and chronic Helicobacter hepaticus induced colitis in dectin-1 deficient mice. Results We show that the mouse intestinal microbiota contains fungi and the cytokine responses towards this microbiota were significantly reduced in dectin-1 deficient macrophages. However, in two different colitis models no significant differences in the course of inflammation were found in dectin-1 deficient mice compared to wild type mice. Conclusions Together our data suggest that, although at the immune cell level there is a difference in response towards the intestinal flora in dectin-1 deficient macrophages, during intestinal inflammation this response seems to be redundant since dectin-1 deficiency in mice does not affect intestinal inflammation in experimental colitis.

  3. Effects of Intestinal Trefoil Factor on Colonic Mucosa in Experimental Colitis of Rats

    Institute of Scientific and Technical Information of China (English)

    YANG Tian; ZOU Kaifang; QIAN Wei

    2005-01-01

    Summary: In order to investigate the protective effects of intestinal trefoil factor (ITF) on colonic mucosa in experimental colitis of rats, ITF was detected by RT-PCR and immunohistochemistry at different time points. Three days after colitis induction, rats were treated with either 0.9 % saline solution or rhITF. Pathological changes and the expression of iNOS mRNA, NO, MDA and SOD were measured respectively. It was found that ITF was mainly located in goblet cells, significantly higher in model group than in normal group (P<0.05). rhITF could increase the iNOS mRNA expression and NO contents, and there was statistically significant difference between rhITF group and model group (P<0.05). rhITF also caused an increase of MDA and a decrease of SOD, but there was no significant difference between two groups. These results indicated that ITF has apparent therapeutic effects in ulcerative colitis, which may be associated with iNOS and NO.

  4. Preventive effect of the microalga Chlamydomonas debaryana on the acute phase of experimental colitis in rats.

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    Avila-Román, Javier; Talero, Elena; Alcaide, Antonio; Reyes, Carolina de Los; Zubía, Eva; García-Mauriño, Sofía; Motilva, Virginia

    2014-10-14

    Inflammatory bowel diseases (IBD) are characterised by chronic uncontrolled inflammation of intestinal mucosa. Diet and nutritional factors have emerged as possible interventions for IBD. Microalgae are rich sources of n-3 PUFA and derived oxylipins. Oxylipins are lipid mediators involved in the resolution of many inflammatory disorders. The aim of the present study was to investigate the effects of the oxylipin-containing biomass of the microalga Chlamydomonas debaryana and its major oxylipin constituent, (9Z,11E,13S,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid ((13S)-HOTE), on acute 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Lyophilised microalgal biomass and (13S)-HOTE were administered by oral route 48, 24 and 1 h before the induction of colitis and 24 h later, and the rats were killed after 48 h. The treatment with the lyophilised microalga and (13S)-HOTE improved body-weight loss and colon shortening, as well as attenuated the extent of colonic damage and increased mucus production. Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase levels induced by TNBS, were also reduced after the administration of the lyophilised microalga or (13S)-HOTE. The anti-inflammatory effects of these treatments were confirmed by the inhibition of colonic TNF-α production. Moreover, lyophilised microalga or (13S)-HOTE down-regulated cyclo-oxygenase-2 and inducible nitric oxide synthase expression. The present study was the first to show the prophylactic effects of a lyophilised biomass sample of the microalga C. debaryana and the oxylipin (13S)-HOTE on TNBS-induced acute colitis in rats. Our findings suggest that the microalga C. debaryana or derived oxylipins could be used as nutraceuticals in the treatment of the active phase of IBD.

  5. Analyzing Beneficial Effects of Nutritional Supplements on Intestinal Epithelial Barrier Functions During Experimental Colitis.

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    Vargas Robles, Hilda; Castro Ochoa, Karla Fabiola; Nava, Porfirio; Silva Olivares, Angélica; Shibayama, Mineko; Schnoor, Michael

    2017-01-05

    Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic relapsing disorders of the intestines. They cause severe problems, such as abdominal cramping, bloody diarrhea, and weight loss, in affected individuals. Unfortunately, there is no cure yet, and treatments only aim to alleviate symptoms. Current treatments include anti-inflammatory and immunosuppressive drugs that may cause severe side effects. This warrants the search for alternative treatment options, such as nutritional supplements, that do not cause side effects. Before their application in clinical studies, such compounds must be rigorously tested for effectiveness and security in animal models. A reliable experimental model is the dextran sulfate sodium (DSS) colitis model in mice, which reproduces many of the clinical signs of ulcerative colitis in humans. We recently applied this model to test the beneficial effects of a nutritional supplement containing vitamins C and E, L-arginine, and ω3-polyunsaturated fatty acids (PUFA). We analyzed various disease parameters and found that this supplement was able to ameliorate edema formation, tissue damage, leukocyte infiltration, oxidative stress, and the production of pro-inflammatory cytokines, leading to an overall improvement in the disease activity index. In this article, we explain in detail the correct application of nutritional supplements using the DSS colitis model in C57Bl/6 mice, as well as how disease parameters such as histology, oxidative stress, and inflammation are assessed. Analyzing the beneficial effects of different diet supplements may then eventually open new avenues for the development of alternative treatment strategies that alleviate IBD symptoms and/or that prolong the phases of remission without causing severe side effects.

  6. Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota.

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    Peris Mumbi Munyaka

    Full Text Available Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota.Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted.ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels.The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers.

  7. Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis

    Institute of Scientific and Technical Information of China (English)

    Malgorzata Zwolinska-Wcislo; Tomasz Brzozowski; Agata Ptak-Belowska; Aneta Targosz; Katarzyna Urbanczyk; Slawomir Kwiecien; Zbigniew Sliwowski

    2011-01-01

    AIM: To determine the eff ect of non-selective cyclooxygenase (COX) inhibitors, selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis. METHODS: Rats with 2,4,6 trinitrobenzenesulfonic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle, aspirin (ASA) (a nonselective COX inhibitor), celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days. The area of colonic lesions, colonic blood flow (CBF), myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2, inducible form of nitric oxide synthase (iNOS), IL-1β and tumor necrosis factor (TNF)-α were assessed. The eff ects of glyceryl trinitrate (GTN), a NO donor, and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5- tetramethyl-1H-imidazolyl-1-oxy-3-oxide, onopotassium salt (carboxy-PTIO), a NO scavenger, administered without and with ASA or NO-ASA, and the involvement of capsaicin-sensitive aff erent nerves in the mechanism of healing the experimental colitis was also determined. RESULTS: Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF, a significant rise in colonic weight, MPO activity and plasma IL.1β and TNF-α levels. These eff ects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)- 3-(trifluoromethyl)-1H-pyrazole (SC-560), but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E2 (PGE2) analog. Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NOx content and CBF, suppression of MPO and downregulation of COX-2, iNOS, IL-1β and TNF-α mRNAs. Treatment with GTN, the NO donor, significantly inhibited the ASA-induced colonic lesions and increased CBF, while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASAinduced improvement of colonic healing and the accompanying increase in the CBF. These eff ects were restored by co

  8. Adoptive transfer of helminth antigen-pulsed dendritic cells protects against the development of experimental colitis in mice.

    Science.gov (United States)

    Matisz, Chelsea E; Leung, Gabriella; Reyes, Jose Luis; Wang, Arthur; Sharkey, Keith A; McKay, Derek M

    2015-11-01

    Infection with helminth parasites and treatment with worm extracts can suppress inflammatory disease, including colitis. Postulating that dendritic cells (DCs) participated in the suppression of inflammation and seeking to move beyond the use of helminths per se, we tested the ability of Hymenolepis diminuta antigen-pulsed DCs to suppress colitis as a novel cell-based immunotherapy. Bone marrow derived DCs pulsed with H. diminuta antigen (HD-DCs), or PBS-, BSA-, or LPS-DCs as controls, were transferred into wild-type (WT), interleukin-10 (IL-10) knock-out (KO), and RAG-1 KO mice, and the impact on dinitrobenzene sulphonic acid (DNBS)-induced colitis and splenic cytokine production assessed 72 h later. Mice receiving HD-DCs were significantly protected from DNBS-induced colitis and of the experimental groups only these mice displayed increased Th2 cytokines and IL-10 production. Adoptive transfer of HD-DCs protected neither RAG-1 nor IL-10 KO mice from DNBS-colitis. Furthermore, the transfer of CD4(+) splenocytes from recipients of HD-DCs protected naïve mice against DNBS-colitis, in an IL-10 dependent manner. Thus, HD-DCs are a novel anti-colitic immunotherapy that can educate anti-colitic CD4(+) T cells: mechanistically, the anti-colitic effect of HD-DCs requires that the host has an adaptive immune response and the ability to mobilize IL-10.

  9. Mitogen-activated protein kinase pathways contribute to hypercontractility and increased Ca2+ sensitization in murine experimental colitis.

    Science.gov (United States)

    Ihara, Eikichi; Beck, Paul L; Chappellaz, Mona; Wong, Josee; Medlicott, Shaun A; MacDonald, Justin A

    2009-05-01

    Inflammatory bowel disease (IBD) is associated with intestinal smooth muscle dysfunction. Many smooth muscle contractile events are associated with alterations in Ca(2+)-sensitizing pathways. The aim of the present study was to assess the effect of colitis on Ca(2+) sensitization and the signaling pathways responsible for contractile dysfunction in murine experimental colitis. Colitis was induced in BALB/c mice by providing 5% dextran sulfate sodium (DSS) in drinking water for 7 days. Contractile responses of colonic circular smooth muscle strips to 118 mM K(+) and carbachol (CCh) were assessed. DSS induced a T(H)2 colitis [increased interleukin (IL)-4 and IL-6] with no changes in T(H)1 cytokines. Animals exposed to DSS had increased CCh-induced contraction (3.5-fold) and CCh-induced Ca(2+)-sensitization (2.2-fold) responses in intact and alpha-toxin permeabilized colonic smooth muscle, respectively. The contributions of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) to CCh-induced contractions were significantly increased during colitis. Ca(2+)-independent contraction induced by microcystin was potentiated (1.5-fold) in mice with colitis. ERK and p38MAPK (but not Rho-associated kinase) contributed to this potentiation. ERK1/2 and p38MAPK expression were increased in the muscularis propria of colonic tissue from both DSS-treated mice and patients with IBD (ulcerative colitis > Crohn's disease). Murine T(H)2 colitis resulted in colonic smooth muscle hypercontractility with increased Ca(2+) sensitization. Both ERK and p38MAPK pathways contributed to this contractile dysfunction, and expression of these molecules was altered in patients with IBD.

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

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    Aguilar-Nascimento J.E.

    1999-01-01

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

  11. Oroxyloside prevents dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB pathway through PPARγ activation.

    Science.gov (United States)

    Wang, Xiaoping; Sun, Yang; Zhao, Yue; Ding, Youxiang; Zhang, Xiaobo; Kong, Lingyi; Li, Zhiyu; Guo, Qinglong; Zhao, Li

    2016-04-15

    Oroxyloside, as a metabolite of oroxylin A, may harbor various beneficial bioactivities which have rarely been reported in the previous studies. Here we established the dextran sulfate sodium (DSS)-induced experimental colitis and evaluated the anti-inflammatory effect of oroxyloside in vivo. As a result, oroxyloside attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. Furthermore, oroxyloside inhibited inflammatory cell infiltration and decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities as well. The production of pro-inflammatory cytokines in serum and colon was also significantly reduced by oroxyloside. We unraveled the underlying mechanisms that oroxyloside inhibited NF-κB pathway by activating Peroxisome Proliferator-Activated Receptor γ (PPARγ) to attenuate DSS-induced colitis. Moreover, we investigated the anti-inflammatory effect and mechanisms of oroxyloside in the mouse macrophage cell line RAW264.7 and bone marrow derived macrophages (BMDM). Oroxyloside decreased several LPS-induced inflammatory cytokines, including IL-1β, IL-6 and TNF-α in RAW264.7 and BMDM. We also found that oroxyloside inhibited LPS-induced activation of NF-κB signaling pathway via activating PPARγ in RAW 264.7 and BMDM. Docking study showed that oroxyloside could bind with PPARγ. GW9662, the inhibitor of PPARγ, and PPARγ siRNA transfection blocked the effect of oroxyloside on PPARγ activation. Our study suggested that oroxyloside prevented DSS-induced colitis by inhibiting NF-κB pathway through PPARγ activation. Therefore, oroxyloside may be a promising and effective agent for inflammatory bowel disease (IBD).

  12. Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

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    Wu, Xue-Feng; Wu, Xing-Xin; Guo, Wen-Jie; Luo, Qiong [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Gu, Yan-Hong [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Shen, Yan; Tan, Ren-Xiang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Sun, Yang, E-mail: yangsun@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

    2012-09-15

    In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation. Highlights: ► Cerebroside D, a glycoceramide compound, alleviated DSS induced colitis. ► The mechanism of the compound involved multiple effects against activated T cells. ► It regulated cytokine profiles in mice with experimental colitis. ► It prevented T cells from entering S and G2/M phases during activation. ► It led to apoptosis of activated T cells with the cleavage of caspases and PARP.

  13. Huang Qi Jian Zhong Pellet Attenuates TNBS-Induced Colitis in Rats via Mechanisms Involving Improvement of Energy Metabolism.

    Science.gov (United States)

    Liu, Duan-Yong; Pan, Chun-Shui; Liu, Yu-Ying; Wei, Xiao-Hong; Zhou, Chang-Man; Sun, Kai; He, Ke; Li, Chong; Yan, Li; Fan, Jing-Yu; Wang, Chuan-She; Hibi, Toshifumi; Liu, Hong-Ning; Han, Jing-Yan

    2013-01-01

    Huang Qi Jian Zhong Pellet (HQJZ) is a famous Chinese medicine formula for treatment of various gastrointestinal tract diseases. This study investigated the role of HQJZ in 2,4,6-trinitrobenzene sulfonic acid- (TNBS-) induced colitis and its underlying mechanism. Colonic mucosal injury was induced by TNBS in the Sprague-Dawley rats. In the HQJZ treatment group, HQJZ was administered (2 g/kg) for 14 days starting from day 1 after TNBS infusion. Colonic mucosal injury occurred obviously 1 day after TNBS challenge and did not recover distinctively until day 15, including an increase in macro- and microscopic scores, a colonic weight index, a decrease in colonic length, a number of functional capillaries, and blood flow. Inverted intravital microscopy and ELISA showed colonic microcirculatory disturbances and inflammatory responses after TNBS stimulation, respectively. TNBS decreased occludin, RhoA, and ROCK-I, while increasing Rac-1, PAK-1, and phosphorylated myosin light chain. In addition, ATP content and ATP5D expression in colonic mucosa decreased after TNBS challenge. Impressively, treatment with HQJZ significantly attenuated all of the alterations evoked by TNBS, promoting the recovery of colonic injury. The present study demonstrated HQJZ as a multitargeting management for colonic mucosal injury, which set in motion mechanisms involving improvement of energy metabolism.

  14. Huang Qi Jian Zhong Pellet Attenuates TNBS-Induced Colitis in Rats via Mechanisms Involving Improvement of Energy Metabolism

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    Duan-Yong Liu

    2013-01-01

    Full Text Available Huang Qi Jian Zhong Pellet (HQJZ is a famous Chinese medicine formula for treatment of various gastrointestinal tract diseases. This study investigated the role of HQJZ in 2,4,6-trinitrobenzene sulfonic acid- (TNBS- induced colitis and its underlying mechanism. Colonic mucosal injury was induced by TNBS in the Sprague-Dawley rats. In the HQJZ treatment group, HQJZ was administered (2 g/kg for 14 days starting from day 1 after TNBS infusion. Colonic mucosal injury occurred obviously 1 day after TNBS challenge and did not recover distinctively until day 15, including an increase in macro- and microscopic scores, a colonic weight index, a decrease in colonic length, a number of functional capillaries, and blood flow. Inverted intravital microscopy and ELISA showed colonic microcirculatory disturbances and inflammatory responses after TNBS stimulation, respectively. TNBS decreased occludin, RhoA, and ROCK-I, while increasing Rac-1, PAK-1, and phosphorylated myosin light chain. In addition, ATP content and ATP5D expression in colonic mucosa decreased after TNBS challenge. Impressively, treatment with HQJZ significantly attenuated all of the alterations evoked by TNBS, promoting the recovery of colonic injury. The present study demonstrated HQJZ as a multitargeting management for colonic mucosal injury, which set in motion mechanisms involving improvement of energy metabolism.

  15. Fisetin, a dietary flavonoid, ameliorates experimental colitis in mice: Relevance of NF-κB signaling.

    Science.gov (United States)

    Sahu, Bidya Dhar; Kumar, Jerald Mahesh; Sistla, Ramakrishna

    2016-02-01

    Fisetin, a dietary flavonoid, is commonly found in many fruits and vegetables. Although studies indicate that fisetin has an anti-inflammatory property, little is known about its effects on intestinal inflammation. The present study investigated the effects of the fisetin on dextran sulphate sodium (DSS)-induced murine colitis, an animal model that resembles human inflammatory bowel disease. Fisetin treatment to DSS-exposed mice significantly reduced the severity of colitis and alleviated the macroscopic and microscopic signs of the disease. Moreover, fisetin reduced the levels of myeloperoxidase activity, the production of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) and the expressions of COX-2 and iNOS in the colon tissues. Further studies revealed that fisetin suppressed the activation of NF-κB (p65) by inhibiting IκBα phosphorylation and NF-κB (p65)-DNA binding activity and attenuated the phosphorylation of Akt and the p38, but not ERK and JNK MAPKs in the colon tissues of DSS-exposed mice. In addition, DSS-induced decline in reduced glutathione (GSH) and the increase in malondialdehyde (MDA) levels were significantly restored by oral fisetin. Furthermore, the results from in vitro studies showed that fisetin significantly reduced the pro-inflammatory cytokine and mediator release and suppressed the degradation and phosphorylation of IκBα with subsequent nuclear translocation of NF-κB (p65) in lipopolysaccharide (LPS)-stimulated mouse primary peritoneal macrophages. These results suggest that fisetin exerts anti-inflammatory activity via inhibition of Akt, p38 MAPK and NF-κB signaling in the colon tissues of DSS-exposed mice. Thus, fisetin may be a promising candidate as pharmaceuticals or nutraceuticals in the treatment of inflammatory bowel disease.

  16. Protective effects of citicoline on TNBS-induced experimental colitis in rats.

    Science.gov (United States)

    Ek, Rauf Onur; Serter, Mukadder; Ergin, Kemal; Cecen, Serpil; Unsal, Cengiz; Yildiz, Yuksel; Bilgin, Mehmet D

    2014-01-01

    The aim of this study was to investigate the effects of citicoline on the development of colitis and antioxidant parameters in rats subjected to tribenzene sulfonic acid (TNBS)-induced colitis. Twenty four Wistar Albino female rats were divided into four subgroups (n=6) (control, colitis control, colitis + 50 mg/kg citicoline, colitis + 250 mg/kg citicoline). Colitis was induced using an enema of TNBS and ethanol; following which citicoline was administrated for 3 days and effects of citicoline was subsequently evaluated. Based on microscopic damage scores, there was no difference between rats of the TNBS-colitis and 50 mg/kg citicoline treated groups, whereas treatment with 250 mg/kg citicoline, caused significant reduction in colon injury compared to that observed in rats of TNBS-colitis group. In terms of the biochemical analyses, myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione (GSH), and IL-6 levels in rats from 250 mg/kg citicoline group were significantly different from that TNBS-colitis group. The levels of MPO, MDA, GSH and IL-6 in control rats were also significantly different those of rats in the TNBS-colitis group. Citicoline may have a positive protective effect on the inflammatory bowel disease treatment process and could, therefore, be used as an adjunct therapy in colitis. These effects of citicoline may exist through anti-inflammatory and antioxidant mechanism.

  17. Expression of alternatively spliced variants of Na-Ca-exchanger-1 in experimental colitis: role in reduced colonic contractility.

    Science.gov (United States)

    Shubair, M; Oriowo, M A; Khan, I

    2012-11-01

    Inflammation-induced colonic motility dysfunction is associated with a disturbance in Ca(2+) ion transporting mechanisms. The main objective of this study was to identify the types of Na-Ca-exchanger-1 (NCX-1) variants expressed in the rat colon, and how this was affected by colitis. In addition, the effect of colitis on the possible involvement of NCX-1 in the reduced carbachol-induced contraction of the rat colon was examined. Colitis was induced in male Sprague-Dawley rats by intra-rectal instillation of trinitrobenzenesulphonic acid (TNBS). Animals were killed on day 5. Colitis was characterized by estimating myeloperoxidase (MPO) activity, body weight, and histological scores. NCX-1 mRNA and protein variants were confirmed by RT-PCR coupled nucleotide sequencing and by Western blot analysis, respectively. Contractility of the colon segments was studied using standard procedure. There was a significant reduction in body weight of TNBS-treated rats. A significant increase in MPO activity and infiltration of inflammatory cells were observed in the inflamed rat colon. RT-PCR coupled nucleotide sequencing identified NCX-1.3 mRNA variant containing exons B and D. Western blot analysis confirmed 70 and 120 kDa molecular mass NCX-1 protein variants in rat colon. There was no significant difference (p > 0.05) in the level of NCX-1 protein variants in inflamed colon as compared to non-colitis controls. Functional experiments demonstrated that NCX in reverse mode played a role in carbachol-induced contraction of colon, and this was not affected by colitis. These findings demonstrated expression of a NCX-1.3 mRNA splice variant, and 70 and 118 kDa protein variants. Inhibition of the reverse mode of NCX-1 was not different in reduced carbachol-induced contraction between the groups. These findings are interpreted to suggest that NCX-1, though expressed did not play a role in reduced contractility in experimental colitis.

  18. Central cholinergic activation of a vagus nerve-to-spleen circuit alleviates experimental colitis.

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    Ji, H; Rabbi, M F; Labis, B; Pavlov, V A; Tracey, K J; Ghia, J E

    2014-03-01

    The cholinergic anti-inflammatory pathway is an efferent vagus nerve-based mechanism that regulates immune responses and cytokine production through α7 nicotinic acetylcholine receptor (α7nAChR) signaling. Decreased efferent vagus nerve activity is observed in inflammatory bowel disease. We determined whether central activation of this pathway alters inflammation in mice with colitis and the mediating role of a vagus nerve-to-spleen circuit and α7nAChR signaling. Two experimental models of colitis were used in C57BL/6 mice. Central cholinergic activation induced by the acetylcholinesterase inhibitor galantamine or a muscarinic acetylcholine receptor agonist treatments resulted in reduced mucosal inflammation associated with decreased major histocompatibility complex II level and pro-inflammatory cytokine secretion by splenic CD11c⁺ cells mediated by α7nAChR signaling. The cholinergic anti-inflammatory efficacy was abolished in mice with vagotomy, splenic neurectomy, or splenectomy. In conclusion, central cholinergic activation of a vagus nerve-to-spleen circuit controls intestinal inflammation and this regulation can be explored to develop novel therapeutic strategies.

  19. COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase

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    José Wander BREGANÓ

    2014-09-01

    Full Text Available Context Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivation of inflammatory bowel disease. With regard to selective cyclo-oxygenase 2 inhibitors, the results are controversial in experimental colitis as well as in human studies. Objectives The aim this study is to compare nonsteroidal anti-inflammatory drugs effects, selective and non selective cyclo-oxygenase 2 inhibitors, in experimental colitis and contribute to the understanding of the mechanisms which nonsteroidal anti-inflammatory drugs provoke colitis exacerbation. Methods Six groups of rats: without colitis, with colitis, and colitis treated with celecoxib, ketoprofen, indometacin or diclofenac. Survival rates, hemoglobin, plasmatic albumin, colonic tissue of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, prostaglandin E2, catalase, superoxide dismutase, thiobarbituric acid-reactive substances, chemiluminescence induced by tert-butil hydroperoxides, and tissue and plasmatic leukotriene B4 were determined. Results The groups treated with diclofenac or indometacin presented lower survival rates, hemoglobin and albumin, higher tissue and plasmatic leukotriene B4 and tissue superoxide dismutase than the group treated with celecoxib. Ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib, concerning to survival rate and albumin. The groups without colitis, with colitis and with colitis treated with celecoxib showed leukotriene B4 and superoxide dismutase lower levels than the groups treated with nonselective cyclo-oxygenase 2 inhibitors. Conclusions Diclofenac and indometacin presented the highest degree of induced colitis exacerbation with nonsteroidal anti-inflammatory drugs, celecoxib did not show colitis exacerbation, and ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib. These results suggest that leukotriene B4 and superoxide dismutase can be

  20. 3-(3-Pyridylmethylidene-2-indolinone Reduces the Severity of Colonic Injury in a Murine Model of Experimental Colitis

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    Kun-Ping Wang

    2015-01-01

    Full Text Available Nrf2 is the key transcription factor regulating the antioxidant response which is crucial for cytoprotection against extracellular stresses. Numerous in vivo studies indicate that Nrf2 plays a protective role in anti-inflammatory response. 3-(3-Pyridylmethylidene-2-indolinone (PMID is a synthesized derivative of 2-indolinone compounds. Our previous study suggested that PMID induces the activation of Nrf2/ARE pathway, then protecting against oxidative stress-mediated cell death. However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes. In the present study we determined if PMID treatment protects mice from dextran sodium sulphate- (DSS- induced colitis. The result suggests that treatment with PMID prior to colitis induction significantly reduced body weight loss, shortened colon length, and decreased disease activity index compared to control mice. Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals. The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation. The expression levels of Nrf2-dependent genes such as HO-1, NQO1, and Nrf2 were increased in PMID pretreated mice. However, PMID pretreatment did not prevent DSS-induced colitis in Nrf2 knockout mice. These data indicate that PMID pretreatment in mice confers protection against DSS-induced colitis in Nrf2-dependent manner, suggesting a potential role of PMID in anti-inflammatory response.

  1. β7-Integrin exacerbates experimental DSS-induced colitis in mice by directing inflammatory monocytes into the colon.

    Science.gov (United States)

    Schippers, A; Muschaweck, M; Clahsen, T; Tautorat, S; Grieb, L; Tenbrock, K; Gaßler, N; Wagner, N

    2016-03-01

    Leukocyte recruitment is pivotal for the initiation and perpetuation of inflammatory bowel disease (IBD) and controlled by the specificity and interactions of chemokines and adhesion molecules. Interactions of the adhesion molecules α4β7-integrin and mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) promote the accumulation of pathogenic T-cell populations in the inflamed intestine. We aimed to elucidate the significance of β7-integrin expression on innate immune cells for the pathogenesis of IBD. We demonstrate that β7-integrin deficiency protects recombination-activating gene-2 (RAG-2)-deficient mice from dextran sodium sulfate (DSS)-induced colitis and coincides with decreased numbers of colonic effector monocytes. We also show that β7-integrin is expressed on most CD11b(+)CD64(low)Ly6C(+) bone marrow progenitors and contributes to colonic recruitment of these proinflammatory monocytes. Importantly, adoptive transfer of CD115(+) wild-type (WT) monocytes partially restored the susceptibility of RAG-2/β7-integrin double-deficient mice to DSS-induced colitis, thereby demonstrating the functional importance of β7-integrin-expressing monocytes for the development of DSS colitis. We also reveal that genetic ablation of MAdCAM-1 ameliorates experimental colitis in RAG-2-deficient mice as well. In summary, we demonstrate a previously unknown role of α4β7-integrin-MAdCAM-1 interactions as drivers of colitis by directing inflammatory monocytes into the colon.

  2. The intestinal epithelium during damage and regeneration : cell type-specific responses in experimental colitis and after cytostatic drug treatment

    NARCIS (Netherlands)

    I.B. Renes (Ingrid)

    2002-01-01

    textabstractIn the first part of this thesis the role of the colonic epithelium and in particular its associated mucus-layer during IBD and in several experimental colitis models is discussed (Chapter 2). In Chapter 3-5 our investigations regarding the colonic epithelium in rat during the different

  3. Melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, attenuates TNBS-induced colitis in mice.

    Science.gov (United States)

    Zielińska, Marta; Jarmuż, Agata; Sałaga, Maciej; Kordek, Radzisław; Laudon, Moshe; Storr, Martin; Fichna, Jakub

    2016-05-01

    Melatonin is known as a strong antioxidant and possesses anti-inflammatory properties. Recently, melatonin was shown to improve colitis in animal models of inflammatory bowel diseases. The aim of the present study was to characterize the role of melatonin receptors (MT) in the anti-inflammatory effect of melatonin and to assess the anti-inflammatory potential of two novel MT receptor agonists, Neu-P11 and Neu-P67, in the mouse model of trinitrobenzenesulfonic acid (TNBS)-induced colitis. Colitis was induced on day 1 by intracolonic (i.c.) administration of TNBS in 30 % ethanol in saline. Melatonin (4 mg/kg, per os (p.o.)), Neu-P11 (20 mg/kg, p.o.; 50 mg/kg, intraperitoneally (i.p.), 50 mg/kg, i.c.), and Neu-P67 (20 mg/kg, p.o.) were given twice daily for 3 days. Luzindole (5 mg/kg, i.p.) was injected 15 min prior to melatonin administration. On day 4, macroscopic and microscopic damage scores were assessed and myeloperoxidase (MPO) activity quantified using O-dianisidine-based assay. Melatonin significantly attenuated colitis in mice, as indicated by the macroscopic score (1.90 ± 0.34 vs. 3.82 ± 0.62 for melatonin- and TNBS-treated mice, respectively), ulcer score (0.87 ± 0.18 vs. 1.31 ± 0.19, respectively), and MPO activity (4.68 ± 0.70 vs.6.26 ± 0.94, respectively). Luzindole, a MT receptor antagonist, did not inhibit the anti-inflammatory effect of melatonin (macroscopic score 1.12 ± 0.22, ulcer score 0.50 ± 0.16); however, luzindole increased MPO activity (7.57 ± 1.05). MT receptor agonists Neu-P11 and Neu-P67 did not improve inflammation induced by TNBS. Melatonin, but not MT receptor agonists, exerts potent anti-inflammatory action in acute TNBS-induced colitis. Our data suggests that melatonin attenuates colitis by additional, MT receptor-independent pathways.

  4. Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jian; Zhang, Lin [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Dai, Weiqi [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Mao, Yuqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Li, Sainan [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Wang, Jingjie; Li, Huanqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Guo, Chuanyong [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Fan, Xiaoming, E-mail: xiaomingfan57@sina.com [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China)

    2015-02-27

    Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys{sup 3}]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation.

  5. Cinnamon extract suppresses experimental colitis through modulation of antigen-presenting cells

    Institute of Scientific and Technical Information of China (English)

    Ho-Keun Kwon; Zee Yong Park; Sin-Hyeog Im; Ji-Sun Hwang; Choong-Gu Lee; Jae-Seon So; Anupama Sahoo; Chang-Rok Im; Won Kyung Jeon; Byoung Seob Ko; Sung Haeng Lee

    2011-01-01

    AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells. METHODS:Cinnamon extract was used to treat murine macrophage cell line (Raw 264.7),mouse primary antigen-presenting cells (APCs,MHCII+) and CD11c+ dendritic cells to analyze the effects of cinnamon extract on APC function.The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production,and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry.In addition,the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H3]-thymidine incorporation and cytokine analysis,respectively. To confirm the anti-inflammatory effects of cinnamon extract in vivo ,cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid.The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms,histological analysis and cytokine expression profiles in inflamed tissue. RESULTS:Treatment with cinnamon extract inhibited maturation of MHCII+ APCs or CD11c+ dendritic cells (DCs) by suppressing expression of co-stimulatory molecules (B7.1,B7.2,ICOS-L),MHCII and cyclooxygenase (COX)-2.Cinnamon extract induced regulatory DCs (rDCs) that produce low levels of pro-inflammatory cytokines [interleukin (IL)-1β,IL-6,IL-12,interferon (IFN)-γ and tumor necrosis factor (TNF)-α] while expressing high levels of immunoregulatory cytokines (IL-10 and transforming growth factor-β).In addition, rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation,and converted CD4+ T cells into IL-10high CD4+ T cells.Furthermore,oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro

  6. Tea tree oil attenuates experimental contact dermatitis.

    Science.gov (United States)

    Wallengren, Joanna

    2011-07-01

    Herbs and minerals have been used in clinical dermatology for hundreds of years and herbal ingredients are becoming increasingly popular with the public in treatment of various dermatological conditions characterised by inflammation and pruritus. The aim of this study was to compare the efficacy of traditional topical therapeutic agents with a moderate potency topical glucocorticoid on experimental contact dermatitis and contact urticaria. The effects of ichthammol 10% pet, zinc oxide 20% pet, camphor 20% pet, levomenthol 10% pet, tea tree oil 20 or 50% and clobetason butyrate 0.05% ointment were studied in the following experimental models: elicitation of allergic contact dermatitis to nickel, irritant contact dermatitis to benzalkonium chloride, and in immediate reactions to histamine and benzoic acid (non-immunological contact utricaria) respectively. Delayed reactions were evaluated using a clinical scoring system and immediate reactions were estimated by planimetry. Histamine-induced pruritus was evaluated using VAS. Tea tree oil reduced allergic contact dermatitis by 40.5% (p = 0.003), zinc oxide by 17.4% (p = 0.04) and clobetason butyrate by 23.5% (p = 0.01). Zinc oxide reduced histamine induced flare by 18.5% (p = 0.01), ichthammol by 19.2% (p = 0.02) and clobetason butyrate by 44.1% (p = 0.02). Irritant contact dermatitis and non-immunological contact urticaria were not influenced by the pre-treatments. Pruritus induced by histamine also remained unchanged. In conclusion, tea tree oil seems to be a more effective anti-eczematic agent than zinc oxide and clobetasone butyrate, while clobetasone butyrate is superior to both ichthammol and zinc oxide in topical treatment of urticarial reactions.

  7. Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function.

    Science.gov (United States)

    Xu, Bin; Li, Yan-Li; Xu, Ming; Yu, Chang-Chun; Lian, Meng-Qiao; Tang, Ze-Yao; Li, Chuan-Xun; Lin, Yuan

    2017-03-06

    Geniposide is an iridoid glycosides purified from the fruit of Gardenia jasminoides Ellis, which is known to have antiinflammatory, anti-oxidative and anti-tumor activities. The present study aimed to investigate the effects of geniposide on experimental rat colitis and to reveal the related mechanisms. Experimental rat colitis was induced by rectal administration of a TNBS solution. The rats were treated with geniposide (25, 50 mg·kg(-1)·d(-1), ig) or with sulfasalazine (SASP, 100 mg·kg(-1)·d(-1), ig) as positive control for 14 consecutive days. A Caco-2 cell monolayer exposed to lipopolysaccharides (LPS) was used as an epithelial barrier dysfunction model. Transepithelial electrical resistance (TER) was measured to evaluate intestinal barrier function. In rats with TNBS-induced colitis, administration of geniposide or SASP significantly increased the TNBS-decreased body weight and ameliorated TNBS-induced experimental colitis and related symptoms. Geniposide or SASP suppressed inflammatory cytokine (TNF-α, IL-1β, and IL-6) release and neutrophil infiltration (myeloperoxidase activity) in the colon. In Caco-2 cells, geniposide (25-100 μmol/L) ameliorated LPS-induced endothelial barrier dysfunction via dose-dependently increasing transepithelial electrical resistance (TER). The results from both in vivo and in vitro studies revealed that geniposide down-regulated NF-κB, COX-2, iNOS and MLCK protein expression, up-regulated the expression of tight junction proteins (occludin and ZO-1), and facilitated AMPK phosphorylation. Both AMPK siRNA transfection and AMPK overexpression abrogated the geniposide-reduced MLCK protein expression, suggesting that geniposide ameliorated barrier dysfunction via AMPK-mediated inhibition of the MLCK pathway. In conclusion, geniposide ameliorated TNBS-induced experimental rat colitis by both reducing inflammation and modulating the disrupted epithelial barrier function via activating the AMPK signaling pathway..

  8. Effects of parenteral fish oil lipid emulsions on colon morphology and cytokine expression after experimental colitis.

    Science.gov (United States)

    Garib, Ricardo; Garla, Priscila; Torrinhas, Raquel S; Bertevello, Pedro L; Logullo, Angela F; Waitzberg, Dan L

    2013-01-01

    Objetivo: Estudiar los efectos de los diferentes protocolos de infusión de la emulsion de lípidos de aceite de pescado (Fole) sobre la inflamación aguda en el modelo de colitis en la rata. Material y métodos: Ratas Wistar macho adultas (n = 51) fueron asignados al azar en 5 grupos para recibir infusión parenteral de solución salina (SS) o emulsión de lípidos de aceite de soja (SO), como controles, y Fole compone de: aceite de pescado solo (FO), una mezcla (9:1 v/v) de SO con FO (SO/FO), o 30% de aceite de soja, 30% triglicéridos de cadena media, 25% de aceite de oliva, y 15% de aceite de pescado (SMOF). Después de 72 h de infusión intravenosa, colitis experimental fue inducida con ácido acético. Después de 24 h, las muestras de colon se analizaron para determinar cambios histológicos y citoquinas. Resultados: En relación en el SS grupo, necrosis macroscópica fue menos frecuente en el grupo FO y necrosis histológica fue más frecuente en el grupo de SMOF. Existe una relación directa e inversa de colon interleuquina (IL) -1 e IL-4, respectivamente, con necrosis histológica. En comparación con el grupo SS, en el FO hubo aumento de IL-4 e IFN-gamma y disminución de TNF-alfa, SO/FO disminuyó TNF-alfa, y en el SMOF hubo aumento de IL-1 y la disminución de IL-4. Conclusión: En la colitis inducida por ácido acético, la infusion aislada de Fole compuesto de aceite de pescado por sí solo fue más ventajosa en la atenuacion de la inflamacióndo que la infusión de Fole contiendo otros aceites, y esta diferencia puede ser debida las influencias de su diferente contenido de ácido graso.

  9. Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis.

    Science.gov (United States)

    Becker, Christoph; Dornhoff, Heike; Neufert, Clemens; Fantini, Massimo C; Wirtz, Stefan; Huebner, Sabine; Nikolaev, Alexei; Lehr, Hans-Anton; Murphy, Andrew J; Valenzuela, David M; Yancopoulos, George D; Galle, Peter R; Karow, Margaret; Neurath, Markus F

    2006-09-01

    Although IL-12 and IL-23 share the common p40 subunit, IL-23, rather than IL-12, seems to drive the pathogenesis of experimental autoimmune encephalomyelitis and arthritis, because IL-23/p19 knockout mice are protected from disease. In contrast, we describe in this study that newly created LacZ knockin mice deficient for IL-23 p19 were highly susceptible for the development of experimental T cell-mediated TNBS colitis and showed even more severe colitis than wild-type mice by endoscopic and histologic criteria. Subsequent studies revealed that dendritic cells from p19-deficient mice produce elevated levels of IL-12, and that IL-23 down-regulates IL-12 expression upon TLR ligation. Finally, in vivo blockade of IL-12 p40 in IL-23-deficient mice rescued mice from lethal colitis. Taken together, our data identify cross-regulation of IL-12 expression by IL-23 as novel key regulatory pathway during initiation of T cell dependent colitis.

  10. Stability of Reference Genes for Messenger RNA Quantification by Real-Time PCR in Mouse Dextran Sodium Sulfate Experimental Colitis.

    Directory of Open Access Journals (Sweden)

    Nour Eissa

    Full Text Available Many animal models have been developed to characterize the complexity of colonic inflammation. In dextran sodium sulfate (DSS experimental colitis in mice the choice of reference genes is critical for accurate quantification of target genes using quantitative real time PCR (RT-qPCR. No studies have addressed the performance of reference genes in mice DSS-experimental colitis. This study aimed to determine the stability of reference genes expression (RGE in DSS-experimental murine colitis.Colitis was induced in male C57BL/6 mice using DSS5% for 5 days, control group received water. RNA was extracted from inflamed and non-inflamed colon. Using RT-qPCR, comparative analysis of 13 RGE was performed according to predefined criteria and relative colonic TNF-α and IL-1β gene expression was determined by calculating the difference in the threshold cycle.Colitis significantly altered the stability of mucosal RGE. Commonly used glyceraldehyde-3-phosphate dehydrogenase (Gapdh, β-actin (Actb, or β2-microglobulin (β2m showed the highest variability within the inflamed and control groups. Conversely, TATA-box-binding protein (Tbp and eukaryotic translation elongation factor 2 (Eef2 were not affected by inflammation and were the most stable genes. Normalization of colonic TNF-α and IL-1β mRNA levels was dependent on the reference gene used. Depending on the genes used to normalize the data, statistical significance varied from significant when TBP / Eef2 were used to non-significant when Gapdh, Actb or β2m were used.This study highlights the appropriate choice of RGE to ensure adequate normalization of RT-qPCR data when using this model. Suboptimal RGE may explain controversial results from published studies. We recommend using Tbp and Eef2 instead of Gapdh, Actb or β2m as reference genes.

  11. Adeno-associated virus mediated delivery of Tregitope 167 ameliorates experimental colitis

    Institute of Scientific and Technical Information of China (English)

    Sander van der Marel; Anna Majowicz; Karin Kwikkers; Richard van Logtenstein; Anje A te Velde; Anne S De Groot; Sybren L Meijer

    2012-01-01

    AIM:To explore the anti-inflammatory potential of adeno-associated virus-mediated delivery of Tregitope 167 in an experimental colitis model.METHODS:The trinitrobenzene sulfonate (TNBS) model of induced colitis was used in Balb/c mice.Subsequently after intravenous adeno-associated virusmediated regulatory T-cell epitopes (Tregitope) delivery,acute colitis was initiated by intra-rectal administration of 1.5 mg TNBS in 40% ethanol followed by a second treatment with TNBS (0.75 mg in 20% ethanol) 8 d later.Control groups included mice not treated with TNBS (healthy control group) and mice treated by TNBS only (diseased group).At the time of sacrifice colon weight,the disease activity index and histology damage score were determined.Immunohistochemical staining of the colonic tissues was performed to asses the cellular infiltrate and the presence of transcription factor forkhead Box-P3 (Foxp3).Thymus,mesenteric lymph nodes,liver and spleen tissue were collected and the corresponding lymphocyte populations were further assessed by flow cytometry analysis for the expression of CD4+ T cell and regulatory T cell associated markers.RESULTS:The Tregitope 167 treated mice gained an average of 4% over their initial body weight at the time of sacrifice.In contrast,the mice treated with TNBS alone (no Tregitope) developed colitis,and lost 4% of their initial body weight at the time of sacrifice (P < 0.01).The body weight increase that had been observed in the mice pre-treated with Tregitope 167 was substantiated by a lower disease activity index and a decreased colon weight as compared to the diseased control group (P < 0.01 and P < 0.001,respectively).Immunohistochemical staining of the colonic tissues for CD4+ showed that inflammatory cell infiltrates were present in TNBS treated mice with or without administration with tregitope 167 and that these cellular infiltrates consisted mainly of CD4+ cells.For both TNBS treated groups CD4+ T cell infiltrates were

  12. Glutamine Supplementation Attenuates Expressions of Adhesion Molecules and Chemokine Receptors on T Cells in a Murine Model of Acute Colitis

    Directory of Open Access Journals (Sweden)

    Yu-Chen Hou

    2014-01-01

    Full Text Available Background. Migration of T cells into the colon plays a major role in the pathogenesis in inflammatory bowel disease. This study investigated the effects of glutamine (Gln supplementation on chemokine receptors and adhesion molecules expressed by T cells in mice with dextran sulfate sodium- (DSS- induced colitis. Methods. C57BL/6 mice were fed either a standard diet or a Gln diet replacing 25% of the total nitrogen. After being fed the diets for 5 days, half of the mice from both groups were given 1.5% DSS in drinking water to induce colitis. Mice were killed after 5 days of DSS exposure. Results. DSS colitis resulted in higher expression levels of P-selectin glycoprotein ligand- (PSGL- 1, leukocyte function-associated antigen- (LFA- 1, and C-C chemokine receptor type 9 (CCR9 by T helper (Th and cytotoxic T (Tc cells, and mRNA levels of endothelial adhesion molecules in colons were upregulated. Gln supplementation decreased expressions of PSGL-1, LFA-1, and CCR9 by Th cells. Colonic gene expressions of endothelial adhesion molecules were also lower in Gln-colitis mice. Histological finding showed that colon infiltrating Th cells were less in the DSS group with Gln administration. Conclusions. Gln supplementation may ameliorate the inflammation of colitis possibly via suppression of T cell migration.

  13. Anti-inflammatory effect of elemental diets with different fat composition in experimental colitis.

    Science.gov (United States)

    Papada, E; Kaliora, A C; Gioxari, A; Papalois, A; Forbes, A

    2014-04-14

    The aim of the present study was to evaluate the effectiveness of two isoenergetic elemental formulae with different fat content in the rat model of trinitrobenzene sulphonic acid (TNBS) colitis that mimics human inflammatory bowel disease. A total of forty-five male Wistar rats were assigned to five groups: (1) control group; (2) TNBS-induced colitis group; (3) TNBS-induced colitis group fed a long-chain TAG (LCT)-rich diet; (4) TNBS-induced colitis group fed a medium-chain TAG (MCT)-rich diet; (5) TNBS-induced colitis group fed a baseline diet and administered infliximab. Nutritional management lasted 12 d before and 4 d after rectal administration of TNBS. Subsequently, the rats were killed, and colonic tissue samples were collected for the assessment of histology, inflammation and oxidative stress. The MCT-rich diet decreased IL-6, IL-8 and intercellular adhesion molecule-1 (ICAM-1) levels and glutathione S-transferase (GST) activity, while the LCT-rich diet reduced only ICAM-1 levels and GST activity (P<0.05). Neither elemental formula affected IL-10 levels. Infliximab reduced IL-8 and ICAM-1 levels and GST activity and increased IL-10 levels (P<0.05). No significant differences were detected in oxidative stress. Histological damage scores differed significantly only between the control and the TNBS-induced colitis group. A MCT-rich formula seems to exert stronger anti-inflammatory effects than a LCT-rich formula in TNBS colitis.

  14. Involvement of lymphocytes in dextran sulfate sodium-induced experimental colitis

    Institute of Scientific and Technical Information of China (English)

    Tae Woon Kim; Jae Nam Seo; Young Ho Suh; Hyo Jin Park; Ju Hyun Kim; Ji Young Kim; Kwon Tk Oh

    2006-01-01

    AIM: To investigate the roles of lymphocytes in the development of dextran sulfate sodium-induced colitis.METHODS: Using various doses of dextran sulfate sodium (DSS), we induced colitis in wild-type B6control and Rag-1 knockout (H-2b haplotype) mice,and evaluated the colitis in terms of symptomatic and histologic parameters, such as weight loss, survival,severity of diarrhea, shortage of colon length and histological changes. Symptomatic parameters were checked daily and histological changes were scored.RESULTS: Although development of colitis in Rag-1knockout mice treated with high dose (5%) of DSS was comparable to that in B6 control mice, colitis progression was much more tolerable in Rag-1 knockout mice compared to than in B6 mice treated with low dose (1.5%)DSS. Symptomatic parameters as well as histopathologic changes were improved in Rag-1 knockout mice.CONCLUSION: These results indicate that the presence of lymphocytes contributes to colitis progression at low dose of DSS stimulation. Lymphocytes may play roles as an aggravating factor in DSS-induced colitis.

  15. Interleukin-19 contributes as a protective factor in experimental Th2-mediated colitis.

    Science.gov (United States)

    Fujimoto, Yasuyuki; Azuma, Yasu-Taka; Matsuo, Yukiko; Kuwamura, Mitsuru; Kuramoto, Nobuyuki; Miki, Mariko; Azuma, Naoki; Teramoto, Midori; Nishiyama, Kazuhiro; Izawa, Takeshi; Nakajima, Hidemitsu; Takeuchi, Tadayoshi

    2017-03-01

    Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. IL-19 is a member of the IL-10 family, and IL-10 plays an important role in inflammatory bowel disease. We have previously shown that IL-19 knockout mice are more susceptible to innate-mediated colitis. Next, we ask whether IL-19 contributes to T cells-mediated colitis. Here, we investigated the role of IL-19 in a mouse model of Th2 cell-mediated colitis. Inflammatory responses in IL-19-deficient mice were assessed using a Th2-mediated colitis induced by oxazolone. The colitis was evaluated by analyzing the body weight loss and histology of the colon. Lymph node cells were cultured in vitro to determine cytokine production. IL-19 knockout mice exacerbated oxazolone-induced colitis by stimulating the transport of inflammatory cells into the colon, and by increasing IgE production and the number of circulating eosinophil. The exacerbation of oxazolone-induced colonic inflammation following IL-19 knockout mice was accompanied by an increased production of IL-4 and IL-9, but no changes in the expression of IL-5 and IL-13 in lymph node cells. IL-19 plays an anti-inflammatory role in the Th2-mediated colitis model, suggesting that IL-19 may represent a potential therapeutic target for reducing colonic inflammation.

  16. Treatment of experimental colitis in mice with LMP-420, an inhibitor of TNF transcription

    Directory of Open Access Journals (Sweden)

    Cianciolo George

    2008-03-01

    Full Text Available Abstract Background LMP-420 is a boronic acid-containing purine nucleoside analogue that transcriptionally inhibits TNF production but is non-cytotoxic to TNF-producing cells. Methods This study investigated the efficacy of LMP-420 as an anti-inflammatory agent in acute and chronic colitis induced by oral administration of dextran sulfate sodium (DSS to mice and in chronic colitis following piroxicam administration to IL-10-deficient mice. The severity of colon inflammation was assessed histologically. TNF levels were measured by enzyme immunoassay. Results Administration of DSS for 7 days resulted in severe acute colitis that was associated with a marked increase in stool and colon tissue TNF levels. Initiation of therapy with intraperitoneal (i.p. LMP-420 on day 4 of DSS exposure decreased colonic TNF to near normal levels on day 7. However, neither i.p. nor oral treatment with LMP-420 affected the development or severity of acute DSS colitis. Initiation of LMP-420 therapy after 3 cycles of DSS administration to establish chronic colitis also had no effect on the severity of chronic colitis. Analysis of colonic TNF combined with longitudinal analysis of TNF and TNF receptor (TNF-RII levels in stool during the development of chronic DSS colitis demonstrated that the initially elevated colonic TNF levels returned to normal despite intense on-going inflammation in mice with chronic colitis. RAG-2-/- mice deficient in T and B cells also developed severe ongoing colitis in response to 3 cycles of DSS, but showed marked differences vs. wild type mice in stool TNF and TNF-RII in response to DSS exposure. Systemic and oral LMP-420 treatment for 16 days decreased colonic TNF levels in IL-10-deficient mice with chronic colitis, with a trend to decreased histologic inflammation for oral LMP-420. Conclusion These studies demonstrate that short-term treatment with a transcriptional inhibitor of TNF production can decrease systemic and local colonic levels

  17. Probiotic yeasts: Anti-inflammatory potential of various non-pathogenic strains in experimental colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Benot; Foligné; Jo■lle; Dewulf; Pascal; Vandekerckove; Georges; Pignède; Bruno; Pot

    2010-01-01

    AIM: To evaluate the in vitro immunomodulation capacity of various non-pathogenic yeast strains and to investigate the ability of some of these food grade yeasts to prevent experimental colitis in mice.METHODS: In vitro immunomodulation was assessed by measuring cytokines [interleukin (IL)-12p70,IL-10,tumor necrosis factor and interferon γ] released by human peripheral blood mononuclear cells after 24 h stimulation with 6 live yeast strains (Saccharomyces ssp.) and with bacterial reference strains.A murine ...

  18. Experimental and theoretical studies on visible light attenuation in water

    CERN Document Server

    Simpson, A; Cho, H J; Liu, H

    2014-01-01

    In this study we describe lab experiments on determining the above water reflectance Rrs coefficient, and the water attenuation coefficient Kd for fresh water. Different types of screens (totally absorbent, gray, etc.) were submerged in water (0-0.6 m) and illuminated from outside. The spectral density of the water leaving radiance was measured for different depths. The results were ran by a code which took into account the geometry of the incident irradiation, the geometry of the screen under water, and boundary conditions at the water surface provided by the radiation transfer theory. From the experimental data and our model we obtain the spectral distribution of the attenuation coefficient for fresh water and compared it with other data in literature. These experiments, performed in the Nonlinear Wave Lab at ERAU# represent just a preliminary calibration of the experimental protocol. More tests with water of different degrees of turbidity, and possibly wave filed at the water surface are in progress and wi...

  19. Allogeneic guinea pig mesenchymal stem cells ameliorate neurological changes in experimental colitis

    OpenAIRE

    Stavely, Rhian; Robinson, Ainsley M.; Miller, Sarah; Boyd, Richard; Sakkal, Samy; Nurgali, Kulmira

    2015-01-01

    Background The use of mesenchymal stem cells (MSCs) to treat inflammatory bowel disease (IBD) is of great interest because of their immunomodulatory properties. Damage to the enteric nervous system (ENS) is implicated in IBD pathophysiology and disease progression. The most commonly used model to study inflammation-induced changes to the ENS is 2,4,6-trinitrobenzene-sulfonate acid (TNBS)-induced colitis in guinea pigs; however, no studies using guinea pig MSCs in colitis have been performed. ...

  20. Intestinal Epithelial Serum Amyloid A Modulates Bacterial Growth In Vitro and Pro-Inflammatory Responses in Mouse Experimental Colitis

    Directory of Open Access Journals (Sweden)

    Wang Yu

    2010-11-01

    Full Text Available Abstract Background Serum Amyloid A (SAA is a major acute phase protein of unknown function. SAA is mostly expressed in the liver, but also in other tissues including the intestinal epithelium. SAA reportedly has anti-bacterial effects, and because inflammatory bowel diseases (IBD result from a breakdown in homeostatic interactions between intestinal epithelia and bacteria, we hypothesized that SAA is protective during experimental colitis. Methods Intestinal SAA expression was measured in mouse and human samples. Dextran sodium sulfate (DSS colitis was induced in SAA 1/2 double knockout (DKO mice and in wildtype controls. Anti-bacterial effects of SAA1/2 were tested in intestinal epithelial cell lines transduced with adenoviral vectors encoding the CE/J SAA isoform or control vectors prior to exposure to live Escherichia coli. Results Significant levels of SAA1/SAA2 RNA and SAA protein were detected by in situ hybridization and immunohistochemistry in mouse colonic epithelium. SAA3 expression was weaker, but similarly distributed. SAA1/2 RNA was present in the ileum and colon of conventional mice and in the colon of germfree mice. Expression of SAA3 was strongly regulated by bacterial lipopolysaccharides in cultured epithelial cell lines, whereas SAA1/2 expression was constitutive and not LPS inducible. Overexpression of SAA1/2 in cultured epithelial cell lines reduced the viability of co-cultured E. coli. This might partially explain the observed increase in susceptibility of DKO mice to DSS colitis. SAA1/2 expression was increased in colon samples obtained from Crohn's Disease patients compared to controls. Conclusions Intestinal epithelial SAA displays bactericidal properties in vitro and could play a protective role in experimental mouse colitis. Altered expression of SAA in intestinal biopsies from Crohn's Disease patients suggests that SAA is involved in the disease process..

  1. Platelet-Derived CCL5 Regulates CXC Chemokine Formation and Neutrophil Recruitment in Acute Experimental Colitis.

    Science.gov (United States)

    Yu, Changhui; Zhang, Songen; Wang, Yongzhi; Zhang, Su; Luo, Lingtao; Thorlacius, Henrik

    2016-02-01

    Accumulating data suggest that platelets not only regulate thrombosis and haemostasis but also inflammatory processes. Platelets contain numerous potent pro-inflammatory compounds, including the chemokines CCL5 and CXCL4, although their role in acute colitis remains elusive. The aim of this study is to examine the role of platelets and platelet-derived chemokines in acute colitis. Acute colitis is induced in female Balb/c mice by administration of 5% dextran sodium sulfate (DSS) for 5 days. Animals receive a platelet-depleting, anti-CCL5, anti-CXCL4, or a control antibody prior to DSS challenge. Colonic tissue is collected for quantification of myeloperoxidase (MPO) activity, CXCL5, CXCL2, interleukin-6 (IL-6), and CCL5 levels as well as morphological analyses. Platelet depletion reduce tissue damage and clinical disease activity index in DSS-exposed animals. Platelet depletion not only reduces levels of CXCL2 and CXCL5 but also levels of CCL5 in the inflamed colon. Immunoneutralization of CCL5 but not CXCL4 reduces tissue damage, CXC chemokine expression, and neutrophil recruitment in DSS-treated animals. These findings show that platelets play a key role in acute colitis by regulating CXC chemokine generation, neutrophil infiltration, and tissue damage in the colon. Moreover, our results suggest that platelet-derived CCL5 is an important link between platelet activation and neutrophil recruitment in acute colitis.

  2. Ameliorative effects of sodium ferulate on experimental colitis and their mechanisms in rats

    Institute of Scientific and Technical Information of China (English)

    Wei-Guo Dong; Shao-Ping Liu; Bao-Ping Yu; Dong-Fang Wu; He-Sheng Luo; Jie-Ping Yu

    2003-01-01

    AIM: To investigate the ameliorative effects of sodium ferulate (SF) on acetic acid-induced colitis and their mechanisms in rats.METHODS: The colitis model of Sprague-Dawley rats was induced by intracolon enema with 8 % (WV) of acetic acid.The experimental animals were randomly divided into model control, 5-aminosalicylic acid therapy group and three dose of SF therapy groups. The 5 groups were treated intracolonically and daily (8:00 am) for 7 days 24 h following the induction of colitis. A normal control group of rats clystered with normal saline instead of acetic acid was also included in the study.Pathological changes of the colonic mucosa were evaluated by the colon mucosa damage index (CMDI) and the histopathological score (HS). The insulted colonic mucosa was sampled for a variety of determinations at the end of experiment when the animals were sacrificed by decapitation.Colonic activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), and levels of malondialdehyde (MDA)and nitric oxide (NO) were assayed with ultraviolet spectrophotometry. Colonic contents of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2)were determined by radioimmunoassay. The expressions of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) p65 proteins in the colonic tissue were detected with immunohistochemistry.RESULTS: Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels,PGE2 and TXB2 contents, as well as the expressions of iNOS,COX-2 and NF-κB p65 proteins in the colonic mucosa,although the colonic SOD activity was significantly decreased compared with the normal control (CMDI: 2.9±0.6 vs0.0±0.0;HS: 4.3±0.9 vs0.7±1.1; MPO: 98.1±26.9 vs24.8±11.5; MDA:57.53±12.36 vs9.21±3.85; NO: 0.331±0.092 vs0.176±0.045;PGE2: 186.2±96.2 vs 42.8±32.8; TXB2

  3. Use of Propolis Hydroalcoholic Extract to Treat Colitis Experimentally Induced in Rats by 2,4,6-Trinitrobenzenesulfonic Acid

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    Cely Cristina Martins Gonçalves

    2013-01-01

    Full Text Available This study focused on the therapeutic effect of a propolis SLNC 106PI extract on experimental colitis. Wistar adult rats received 0.8 mL rectal dose of one of the following solutions: saline (group S, 20 mg TNBS in 50% ethanol (group TNBS, 20 mg TNBS in 50% ethanol and propolis extract in saline (group TNBS-P, propolis extract in saline (group SP, and 20 mg TNBS in 50% ethanol and 50 mg/kg mesalazine (group TNBS-M. The animals were euthanized 7 or 14 days after the colitis induction. Samples of the distal colon were harvested for the analysis of myeloperoxidase (MPO enzyme activity and for morphometric analysis in paraffin-embedded histological sections with hematoxylin-eosin or histochemical staining. The animals treated with TNBS exhibited the typical clinical signs of colitis. Increased MPO activity confirmed the presence of inflammation. TNBS induced the development of megacolon, ulceration, transmural inflammatory infiltrate, and thickened bowel walls. Treatment with propolis moderately reduced the inflammatory response, decreased the number of cysts and abscesses, inhibited epithelial proliferation, and increased the number of goblet cells. The anti-inflammatory activity of the propolis SLNC 106 extract was confirmed by the reductions in both the inflammatory infiltrate and the number of cysts and abscesses in the colon mucosa.

  4. Pregnane X receptor agonists enhance intestinal epithelial wound healing and repair of the intestinal barrier following the induction of experimental colitis.

    Science.gov (United States)

    Terc, Joshua; Hansen, Ashleigh; Alston, Laurie; Hirota, Simon A

    2014-05-13

    The intestinal epithelial barrier plays a key role in the maintenance of homeostasis within the gastrointestinal tract. Barrier dysfunction leading to increased epithelial permeability is associated with a number of gastrointestinal disorders including the inflammatory bowel diseases (IBD) - Crohn's disease and ulcerative colitis. It is thought that the increased permeability in patients with IBD may be driven by alterations in the epithelial wound healing response. To this end considerable study has been undertaken to identify signaling pathways that may accelerate intestinal epithelial wound healing and normalize the barrier dysfunction observed in IBD. In the current study we examined the role of the pregnane X receptor (PXR) in modulating the intestinal epithelial wound healing response. Mutations and reduced mucosal expression of the PXR are associated with IBD, and others have reported that PXR agonists can dampen intestinal inflammation. Furthermore, stimulation of the PXR has been associated with increased cell migration and proliferation, two of the key processes involved in wound healing. We hypothesized that PXR agonists would enhance intestinal epithelial repair. Stimulation of Caco-2 intestinal epithelial cells with rifaximin, rifampicin and SR12813, all potent agonists of the PXR, significantly increased wound closure. This effect was driven by p38 MAP kinase-dependent cell migration, and occurred in the absence of cell proliferation. Treating mice with a rodent specific PXR agonist, pregnenolone 16α-carbonitrile (PCN), attenuated the intestinal barrier dysfunction observed in the dextran sulphate sodium (DSS) model of experimental colitis, an effect that occurred independent of the known anti-inflammatory effects of PCN. Taken together our data indicate that the activation of the PXR can enhance intestinal epithelial repair and suggest that targeting the PXR may help to normalize intestinal barrier dysfunction observed in patients with IBD

  5. Deficiency of Nuclear Receptor Nur77 Aggravates Mouse Experimental Colitis by Increased NFκB Activity in Macrophages.

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    Anouk A J Hamers

    Full Text Available Nuclear receptor Nur77, also referred to as NR4A1 or TR3, plays an important role in innate and adaptive immunity. Nur77 is crucial in regulating the T helper 1/regulatory T-cell balance, is expressed in macrophages and drives M2 macrophage polarization. In this study we aimed to define the function of Nur77 in inflammatory bowel disease. In wild-type and Nur77-/- mice, colitis development was studied in dextran sodium sulphate (DSS- and 2,4,6-trinitrobenzene sulfonic acid (TNBS-induced models. To understand the underlying mechanism, Nur77 was overexpressed in macrophages and gut epithelial cells. Nur77 protein is expressed in colon tissues from Crohn's disease and Ulcerative colitis patients and colons from colitic mice in inflammatory cells and epithelium. In both mouse colitis models inflammation was increased in Nur77-/- mice. A higher neutrophil influx and enhanced IL-6, MCP-1 and KC production was observed in Nur77-deficient colons after DSS-treatment. TNBS-induced influx of T-cells and inflammatory monocytes into the colon was higher in Nur77-/- mice, along with increased expression of MCP-1, TNFα and IL-6, and decreased Foxp3 RNA expression, compared to wild-type mice. Overexpression of Nur77 in lipopolysaccharide activated RAW macrophages resulted in up-regulated IL-10 and downregulated TNFα, MIF-1 and MCP-1 mRNA expression through NFκB repression. Nur77 also strongly decreased expression of MCP-1, CXCL1, IL-8, MIP-1α and TNFα in gut epithelial Caco-2 cells. Nur77 overexpression suppresses the inflammatory status of both macrophages and gut epithelial cells and together with the in vivo mouse data this supports that Nur77 has a protective function in experimental colitis. These findings may have implications for development of novel targeted treatment strategies regarding inflammatory bowel disease and other inflammatory diseases.

  6. Inhibitory Effect of Recombinant IL-25 on the Development of Dextran Sulfate Sodium Induced Experimental Colitis in Mice

    Institute of Scientific and Technical Information of China (English)

    S.S. Salum Mchenga; Danan Wang; Cheng Li; Fengping Shan; Changlong Lu

    2008-01-01

    The role of interleukin 25 (IL-25) in a number of human diseases still has not been extensively studied, here we attempt to evaluate the role of recombinant IL-25 (rIL-25) in the development of dextran sulfate sodium (DSS)induced experimental colitis. Acute colitis was induced in female C57BL/6 mice by oral administration of 2.5% DSS in drinking water ad libitum. At the same time as the start of DSS exposure, mice were injected intraperitoneally with 0.4 μg of rIL-25 or PBS. Then disease activity index (DAI), histological changes and survival rate were observed. The levels of IL-17, IL-23, and TGF-β1 in colon tissues were determined by ELISA, and the production of IL-17 by CD4+/CD8+ T cells was detected by intracellular flow cytometry. In contrast to the DSS treated mice, DSS + rIL-25 treated mice displayed a lower DAI, limited histological changes and prolonged survival. The levels of IL-23 and TGF-β1 were significantly elevated in the DSS + rIL-25 treated mice compared to the DSS treated mice. There was no significant difference in the production of IL-17 in colon tissues and CD4+/CD8+ T cells between the DSS + rIL-25 treated mice and DSS treated mice. Our findings suggest the role of IL-25 in inhibiting development and progression of acute colitis in DSS-induced mouse colitis model. Cellular & Molecular Immunology. 2008;5(6):425-431.

  7. The antiprotozoal drug pentamidine ameliorates experimentally induced acute colitis in mice

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    Esposito Giuseppe

    2012-12-01

    Full Text Available Abstract Background Intestinal inflammation is partly driven by enteroglial-derived S100B protein. The antiprotozoal drug pentamidine directly blocks S100B activity. We aimed to investigate the effect of pentamidine on intestinal inflammation using an animal model of dextran sodium sulphate (DSS-induced acute colitis. Methods Mice were divided into: control group, colitis group (4% DSS for four days and two pentamidine-treated colitis groups (0.8 mg/kg and 4 mg/kg. Anti-inflammatory effect of pentamidine was assessed in colonic tissue by evaluating the disease activity index and the severity of histological changes. Colonic tissue were also used to evaluate cyclooxigenase-2, inducible nitric oxide synthase, S100B, glial fibrillary acidic protein, phosphorylated-p38 MAPkinase, p50, p65 protein expression, malondyaldheyde production, mieloperoxidase activity, and macrophage infiltration. Nitric oxide, prostaglandin E2, interleukin-1 beta, tumor necrosis factor alpha, and S100B levels were detected in plasma samples. Parallel measurements were performed in vitro on dissected mucosa and longitudinal muscle myenteric plexus (LMMP preparations after challenge with LPS + DSS or exogenous S100B protein in the presence or absence of pentamidine. Results Pentamidine treatment significantly ameliorated the severity of acute colitis in mice, as showed by macroscopic evaluation and histological/biochemical assays in colonic tissues and in plasma. Pentamidine effect on inflammatory mediators was almost completely abrogated in dissected mucosa but not in LMMP. Conclusions Pentamidine exerts a marked anti-inflammatory effect in a mice model of acute colitis, likely targeting S100B activity. Pentamidine might be an innovative molecule to broaden pharmacological tools against colitis.

  8. Effect of Scutellariae Radix extract on experimental dextran-sulfate sodium-induced colitis in rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effect of Scutellariae Radix extract (SRE) on ulcerative colitis (UC) in rats induced by dextran-sulfate sodium (DSS).METHODS: Colitis was induced in male Sprague-Dawley (SD) rats (170-180 g) by 4% dextran sulfate sodium (DSS, wt/v; MW 54000) in drinking water for 8 d. The treated rats received 4% DSS and SRE orally (100 mg/kg per day). Control rats received either tap water or SRE only. Macroscopic assessment which included body weight changes, fecal occult blood and stool consistency were determined daily. At the appointed time, the rats were sacrificed and the entire colons were removed. The colon length and the myeloperoxidase (MPO) activity were measured. The severity of colitis was graded by morphological and histological assessments. The ion transport activity of the colonic mucosa was assessed by electrophysiological technique. RESULTS: Rats treated with oral administration of 4% DSS regularly developed clinical and macroscopic signs of colitis. Treatment with SRE relieved the symptoms, including the reduction in body weight, shortening and ulceration of the colon. Administration of SRE also significantly reduced the histological damage induced by DSS. Moreover, the Isc responses of the colonic mucosa to forskolin were suppressed after the induction of colitis. The stimulated ion transport activity of DSS-rats treated with SRE displayed significant improvement in the secretory responsiveness.CONCLUSION: SRE was effective in treating acute DSS -induced ulcerative colitis, as gauged by reduced clinical disease, improved macroscopic and histological damage scores, and enhanced recovery of normal colonic secretory function.

  9. Effects of Dietary Plant Sterols and Stanol Esters with Low- and High-Fat Diets in Chronic and Acute Models for Experimental Colitis.

    Science.gov (United States)

    te Velde, Anje A; Brüll, Florence; Heinsbroek, Sigrid E M; Meijer, Sybren L; Lütjohann, Dieter; Vreugdenhil, Anita; Plat, Jogchum

    2015-10-15

    In this study, we evaluated the effects of dietary plant sterols and stanols as their fatty acid esters on the development of experimental colitis. The effects were studied both in high- and low-fat diet conditions in two models, one acute and another chronic model of experimental colitis that resembles gene expression in human inflammatory bowel disease (IBD). In the first experiments in the high fat diet (HFD), we did not observe a beneficial effect of the addition of plant sterols and stanols on the development of acute dextran sulphate sodium (DSS) colitis. In the chronic CD4CD45RB T cell transfer colitis model, we mainly observed an effect of the presence of high fat on the development of colitis. In this HFD condition, the presence of plant sterol or stanol did not result in any additional effect. In the second experiments with low fat, we could clearly observe a beneficial effect of the addition of plant sterols on colitis parameters in the T cell transfer model, but not in the DSS model. This positive effect was related to the gender of the mice and on Treg presence in the colon. This suggests that especially dietary plant sterol esters may improve intestinal inflammation in a T cell dependent manner.

  10. Dietary heme adversely affects experimental colitis in rats, despite heat-shock protein induction

    NARCIS (Netherlands)

    Schepens, Marloes A. A.; Vink, Carolien; Schonewille, Arjan J.; Dijkstra, Gerard; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg M. J.

    2011-01-01

    Objective: Research on dietary modulation of inflammatory bowel disease is in its infancy. Dietary heme, mimicking red meat, is cytotoxic to colonic epithelium and thus may aggravate colitis. Alternatively, heme-induced colonic stress might also result in potential protective heat-shock proteins (HS

  11. Protective Effect of Jiechangning (结肠宁)Decoction in Treating Experimental Ulcerative Colitis in Guinea Pigs

    Institute of Scientific and Technical Information of China (English)

    XIONG Wu-jun; QIU Qi-yu; QIU De-kai

    2005-01-01

    Objective:To study the therapeutic effects and mechanism of Jiechangning (结肠宁, JCN)decoction on carrageenan induced experimental ulcerative colitis (UC). Methods: After sensitizing guinea pigs with carrageenan, we established UC animal models by free drinking water containing 2 % acid degraded carrageenan (ADC). JCN decoction was orally administered once a day for 2 weeks after carrageenan treatment. Salicylazosulfapyridine (SASP) and normal saline were given to the other two groups as control. The levels of colon lipid peroxide (LPO), acid phosphatase (ACP)activity and tumor necrosis factor-α (TNF-α)were measured; colitis activity score (CAS) was carried out for assessment of the degree of tissue inflammation and injury; the colonic pathological changes were examined simultaneously with hematoxylin and eosin (HE) and toluidine blue staining used to evaluate the therapeutic effects of JCN decoction and SASP. Results:Experimental colitis models resembling human UC were successfully induced. The levels of tissue LPO, ACP activity and the content of tissue TNF-α were markedly increased in the model group as compared with the normal control group (P<0.01) and were positively correlated with CAS. JCN decoction could reverse these changes like SASP. HE staining showed that JCN decoction and SASP could reduce CAS and the degree of tissue injury, toluidine blue staining revealed that mucosa and submucosa red metachromasia pellets in JCN group and SASP group were markedly fewer than those in the model group. Conclusion: JCN decoction is effective in treating experimental UC, which provides theoretical basis for its clinical application.

  12. Huang Qi Jian Zhong Pellet Attenuates TNBS-Induced Colitis in Rats via Mechanisms Involving Improvement of Energy Metabolism

    OpenAIRE

    Duan-Yong Liu; Chun-Shui Pan; Yu-Ying Liu; Xiao-Hong Wei; Chang-Man Zhou; Kai Sun; Ke He; Chong Li; Li Yan; Jing-Yu Fan; Chuan-She Wang; Toshifumi Hibi; Hong-Ning Liu; Jing-Yan Han

    2013-01-01

    Huang Qi Jian Zhong Pellet (HQJZ) is a famous Chinese medicine formula for treatment of various gastrointestinal tract diseases. This study investigated the role of HQJZ in 2,4,6-trinitrobenzene sulfonic acid- (TNBS-) induced colitis and its underlying mechanism. Colonic mucosal injury was induced by TNBS in the Sprague-Dawley rats. In the HQJZ treatment group, HQJZ was administered (2 g/kg) for 14 days starting from day 1 after TNBS infusion. Colonic mucosal injury occurred obviously 1 day a...

  13. Localized delivery of interferon-β by Lactobacillus exacerbates experimental colitis.

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    Adelle P McFarland

    Full Text Available BACKGROUND: There have been conflicting reports of the role of Type I interferons (IFN in inflammatory bowel disease (IBD. Clinical trials have shown potent efficacy of systemic interferon-beta (IFN-β in inducing remission of ulcerative colitis. Likewise, IFNAR1(-/- mice display an increased sensitivity to dextran sulfate sodium (DSS-induced colitis, suggesting Type I IFN play a protective role during inflammation of the gut. Curiously, however, there have also been reports detailing the spontaneous development of IBD in patients receiving systemic IFN-β therapy for multiple sclerosis or hepatitis. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the effects of local administration of IFN-β on a murine model of colitis, we developed a transgenic Lactobacillus acidophilus strain that constitutively expresses IFN-β (La-IFN-β. While pretreatment of mice with control Lactobacillus (La-EV provided slight protective benefits, La-IFN-β increased sensitivity to DSS. Analysis showed colitic mice pretreated with La-IFN-β had increased production of TNF-α, IFN-γ, IL-17A and IL-13 by intestinal tissues and decreased regulatory T cells (Tregs in their small intestine. Examination of CD103(+ dendritic cells (DCs in the Peyer's patches revealed that IFNAR1 expression was dramatically reduced by La-IFN-β. Similarly, bone marrow-derived DCs matured with La-IFN-β experienced a 3-fold reduction of IFNAR1 and were impaired in their ability to induce Tregs. CONCLUSIONS/SIGNIFICANCE: Our IFNAR1 expression data identifies a correlation between the loss/downregulation of IFNAR1 on DCs and exacerbation of colitis. Our data show that Lactobacillus secreting IFN-β has an immunological effect that in our model results in the exacerbation of colitis. This study underscores that the selection of therapeutics delivered by a bacterial vehicle must take into consideration the simultaneous effects of the vehicle itself.

  14. IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression.

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    José L Reyes

    2016-04-01

    Full Text Available Interleukin (IL-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells, can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS-induced colitis. Here we assessed expulsion of H. diminuta, the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT and IL-22 deficient mice (IL-22-/- ± infection. Interleukin-22-/- mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22-/- mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H. diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22-/- mice that displayed less DNBS (3 mg, ir. 72h-induced colitis. Wild-type mice infected with H. diminuta were protected from colitis, as were infected IL-22-/- mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22-/- mice and blocked the anti-colitic effect of infection with H. diminuta. Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H. diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H. diminuta in a non-permissive host.

  15. IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression.

    Science.gov (United States)

    Reyes, José L; Fernando, Maria R; Lopes, Fernando; Leung, Gabriella; Mancini, Nicole L; Matisz, Chelsea E; Wang, Arthur; McKay, Derek M

    2016-04-01

    Interleukin (IL)-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells), can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we assessed expulsion of H. diminuta, the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT) and IL-22 deficient mice (IL-22-/-) ± infection. Interleukin-22-/- mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22-/- mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H. diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22-/- mice that displayed less DNBS (3 mg, ir. 72h)-induced colitis. Wild-type mice infected with H. diminuta were protected from colitis, as were infected IL-22-/- mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22-/- mice and blocked the anti-colitic effect of infection with H. diminuta. Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H. diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H. diminuta in a non-permissive host.

  16. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nagib, Marwa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Tadros, Mariane G., E-mail: mirogeogo@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); ELSayed, Moushira I. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Khalifa, Amani E. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2013-08-15

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5 days. OLM-M (1, 3 and 10 mg/kg) was administered orally during 21 days prior to the induction of colitis, and for 5 days after. Sulfasalazine (500 mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-α), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects. - Highlights: • Olmesartan medoximil reduced dextran sodium sulphate- induced colitis. • Mechanism involved anti-inflammatory and antioxidant effects dose- dependently. • It suppressed malondialdehyde and restored reduced glutathione levels. • It reduced inflammatory markers levels and histological changes.

  17. Antioxidative potential of a combined therapy of anti TNFα and Zn acetate in experimental colitis

    Institute of Scientific and Technical Information of China (English)

    Michela Barollo; Giacomo Carlo Sturniolo; Valentina Medici; Renata D'Incà; Antara Banerjee; Giuseppe Ingravallo; Marco Scarpa; Surajit Patak; Cesare Ruffolo; Romilda Cardin

    2011-01-01

    AIM: To evaluate whether combination therapy with anti-tumour necrosis factor α (TNFα). Zantibody and Zn acetate is beneficial in dextran sodium sulphate(DSS) colitis. METHODS: Colitis was induced in CD1-Swiss mice with 5% DS for 7 d. The exp erimental mice were th en randomised into the following subgroups: standard diet + DSS treated (induced colitis group); standard diet + DSS + subcutaneous 25. Μg anti-TNFα treated group; Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα; standard diet + DS + subcut aneou s 6.25 μg anti-TNFα treated group and Zn acetate treated group + DS + subcut aneou s 6.25 μg anti-TNFα. Each group of mice was matched with a similar group of sham contro l animals. Macro scop ic and histo logical featur es were scor ed blindly. Homo genates of th e colonic mu cosa were assessed for myeloperoxidase activity as a biochemical marker of inflamm ation and DNA addu cts (8OHdG) as a measur e of ox idative damage. RESULTS: DSS produced submucosal erosions, ulcers, inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFα alone or com bined with zinc. The effect was more pronounced in the latter group. .(vs Zn diet, P < 0.02).Myeloperoxidase activity (vs controls, P < 0.02) and DNA addu cts, greatly elevated in th e DSS fed colitis group (vs controls,. P < 0.05), were significantly redu ced in th e tr eated group s, with a mor e remarkable effect in the group receiving combined therapy (vs standard diet,. P < 0.04). CONCLUSION: DSS induces colonic inflammation which is modulated by the administration of anti-TNFα. Combining anti-TNFα Zwith Zn acetate offers marginal benefit in colitis severity.

  18. Chios mastic fractions in experimental colitis: implication of the nuclear factor κB pathway in cultured HT29 cells.

    Science.gov (United States)

    Papalois, Apostolos; Gioxari, Aristea; Kaliora, Andriana C; Lymperopoulou, Aikaterini; Agrogiannis, George; Papada, Efstathia; Andrikopoulos, Nikolaos K

    2012-11-01

    The Pistacia lentiscus tree gives a resinous exudate called Chios mastic (CM) rich in triterpenoids. CM can be fractionated into acidic and neutral fractions (AF and NF, respectively). Oleanolic acid (OA) is a major triterpenic acid in CM with several antioxidant and anti-inflammatory properties. We have recently shown that CM is beneficial in experimental colitis in the form of powder mixture with inulin, as supplied commercially. However, the bioactive fraction or compound of CM is unidentified. Thus, based on the hypothesis that terpenoids exhibit functional activities via distinguishable pathways, we fractionated CM and applied different fractions or individual OA in experimental colitis. Furthermore, we investigated the mechanism underlying this effect in human colon epithelial cells. CM powder mixture (100 mg/kg of body weight) or the respective CM powder mixture components (i.e., inulin, AF, NF, or OA) were individually administered in trinitrobenzene sulfonic acid-treated rats. Colonic damage was assessed microscopically, and levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and intercellular adhesion molecule-1were measured. A model of inflammation in co-cultured human colon epithelial HT29 cells and monocytes/macrophages was established. Lactate dehydrogenase release and levels of TNF-α, IL-8, and nuclear factor-κB (NF-κB) p65 were measured. In vivo, histological amelioration of colitis and significant regulation in inflammation occurred with CM powder mixture, even at the mRNA level. Although no histological improvement was observed, AF and NF reduced levels of inflammatory markers. Inulin was ineffective. In vitro, CM treatment down-regulated IL-8 and NF-κB p65. Neither fractions nor OA was the bioactive component solely. Most probably, the entire CM rather than its individual fractions reduces inflammation via NF-κB regulation.

  19. R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice.

    Science.gov (United States)

    Schmitz, Katja; de Bruin, Natasja; Bishay, Philipp; Männich, Julia; Häussler, Annett; Altmann, Christine; Ferreirós, Nerea; Lötsch, Jörn; Ultsch, Alfred; Parnham, Michael J; Geisslinger, Gerd; Tegeder, Irmgard

    2014-11-01

    R-flurbiprofen is the non-cyclooxygenase inhibiting R-enantiomer of the non-steroidal anti-inflammatory drug flurbiprofen, which was assessed as a remedy for Alzheimer's disease. Because of its anti-inflammatory, endocannabinoid-modulating and antioxidative properties, combined with low toxicity, the present study assessed R-flurbiprofen in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis in mice. Oral R-flurbiprofen prevented and attenuated primary progressive EAE in C57BL6/J mice and relapsing-remitting EAE in SJL mice, even if the treatment was initiated on or after the first flare of the disease. R-flurbiprofen reduced immune cell infiltration and microglia activation and inflammation in the spinal cord, brain and optic nerve and attenuated myelin destruction and EAE-evoked hyperalgesia. R-flurbiprofen treatment increased CD4(+)CD25(+)FoxP3(+) regulatory T cells, CTLA4(+) inhibitory T cells and interleukin-10, whereas the EAE-evoked upregulation of pro-inflammatory genes in the spinal cord was strongly reduced. The effects were associated with an increase of plasma and cortical endocannabinoids but decreased spinal prostaglandins, the latter likely due to R to S inversion. The promising results suggest potential efficacy of R-flurbiprofen in human MS, and its low toxicity may justify a clinical trial.

  20. Role of nociceptin/orphanin FQ (Noc/oFQ) in murine experimental colitis.

    Science.gov (United States)

    Kato, Shingo; Tsuzuki, Yoshikazu; Hokari, Ryota; Okada, Yoshikiyo; Miyazaki, Junichi; Matsuzaki, Koji; Iwai, Atsuhiro; Kawaguchi, Atsushi; Nagao, Shigeaki; Itoh, Kazuro; Suzuki, Hidekazu; Nabeshima, Toshitaka; Miura, Soichiro

    2005-04-01

    Nociceptin/orphanin (Noc/oFQ), endogenous agonist for nociceptin receptor (NOR), is thought to be a stimulator of neurogenic inflammation. We investigated the possible role of Noc/oFQ in the development of colitis using NOR-deficient mice treated with dextran sulfate sodium (DSS). Colitis was significantly improved in NOR-deficient mice against wild-type mice. Expression level of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and infiltrating cells also significantly decreased in NOR-deficient mice against wild-type mice. Nociceptin expression increased in wild-type mice after DSS treatment. These results suggest stimulation by Noc/oFQ deteriorates colonic inflammation via up-regulation of adhesion molecule.

  1. Novel effects of ectoine, a bacteria-derived natural tetrahydropyrimidine, in experimental colitis.

    Science.gov (United States)

    Abdel-Aziz, Heba; Wadie, Walaa; Abdallah, Dalaal M; Lentzen, Georg; Khayyal, Mohamed T

    2013-05-15

    Evidence suggests an important role of intestinal barrier dysfunction in the etiology of inflammatory bowel disease (IBD). Therefore stabilizing mucosal barrier function constitutes a new therapeutic approach in its management. Ectoine is a compatible solute produced by aerobic chemoheterotrophic and halophilic/halotolerant bacteria, where it acts as osmoprotectant and effective biomembrane stabilizer, protecting the producing cells from extreme environmental stress. Since this natural compound was also shown to prevent inflammatory responses associated with IBD, its potential usefulness was studied in a model of colitis. Groups of rats were treated orally with different doses of ectoine (30-300 mg/kg) or sulfasalazine (reference drug) daily for 11 days. On day 8 colitis was induced by intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid, when overt signs of lesions develop within the next 3 days. On day 12, blood was withdrawn from the retro-orbital plexus of the rats and the animals were sacrificed. The colon was excised and examined macroscopically and microscopically. Relevant parameters of oxidative stress and inflammation were measured in serum and colon homogenates. Induction of colitis led to marked weight loss, significant histopathological changes of the colon, and variable changes in levels of myeloperoxidase, reduced glutathione, malondialdehyde, and all inflammatory markers tested. Treatment with ectoine ameliorated the inflammatory changes in TNBS-induced colitis. This effect was associated with reduction in the levels of TNF-α, IL-1β, ICAM-1, PGE2 and LTB4. The findings suggest that intestinal barrier stabilizers from natural sources could offer new therapeutic measures for the management of IBD.

  2. Protective effect of melatonin on myenteric neuron damage in experimental colitis in rats.

    Science.gov (United States)

    Shang, Boxin; Shi, Haitao; Wang, Xiaoyan; Guo, Xiaoyan; Wang, Nan; Wang, Yan; Dong, Lei

    2016-04-01

    Inflammation of the colon in patients with ulcerative colitis (UC) causes pain and altered motility, at least in part through the damage of the myenteric neurons (MNs). Thus, it is important to evaluate new drugs for UC treatment that could also protect myenteric neurons efficiently. As a well-known neural protective and anti-inflammatory agent, melatonin could protect neurons from damage through the activation of the nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) signaling pathway. Therefore, we investigated the potential protective effect of melatonin against MN damage during colitis induced by 2,4-dinitrobenzene sulfonic acid (DNBS) in rats. Colitis was induced by intracolonic (i.c.) instillation of DNBS and treated with melatonin at a dose of 2.5 mg/kg for 4 days. The damage of MN in the left colon was immunohistochemically evaluated in different groups. Ulcerations and inflammation in the colon were semiquantitatively observed. Myeloperoxidase (MPO), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected to evaluate the inflammatory and oxidative stress status. The protein and mRNA expressions of Nrf2 and heme oxygenase-1 (HO-1) in the colon were detected by Western blot and quantitative polymerase chain reaction (qPCR), respectively. Melatonin partially prevented the loss of MN and alleviated the inflammation and oxidative stress induced by DNBS. In addition, melatonin markedly increased the Nrf2 and HO-1 level in the colitis. These results indicate that melatonin protects MN from damage by reducing inflammation and oxidative stress, effects that are partly mediated by the Nrf2-ARE pathway.

  3. FR167653, a p38 mitogen-activated protein kinase inhibitor, aggravates experimental colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Takashi Nishimura; Akira Andoh; Atsushi Nishida; Makoto Shioya; Yuhsuke Koizumi; Tomoyuki Tsujikawa; Yoshihide Fujiyama

    2008-01-01

    AIM: To investigate the effects of FR167653 on the development of dextran sulfate sodium (DSS)-induced colitis in mice.METHODS: BALB/c mice were fed rodent chow containing 3.5% (wt/wt) DSS. The recipient mice underwent intra-peritoneal injection of vehicles or FR167653 (30 mg/kg per day). The mice were sacrificed on day 14, and the degree of colitis was assessed. Immunohistochemical analyses for CD4+ T cell and F4/80+ macrophage infiltration were also performed. Mucosal o/tokine expression was analyzed by RT-PCR.RESULTS: The body weight loss was more apparent in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. The colon length was shorter in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. Disease activity index and histological colitis score were significantly higher in FR167653- than in vehicle-treated DSS animals. Microscopically, mucosal edema, cellular infiltration (CD4 T cells and F4/80 macrophages), and the disruption of the epithelium were much more severe in FR167653-treated mice than in controls. Mucosal mRNA expression for interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were found to be markedly reduced in FR167653-treated DSS mice.CONCLUSION: Treatment with FR167653 aggravated DSS colitis in mice. This effect was accompanied by a reduction of mucosal IL-1β and TNF-α expression, suggesting a role of p38 mitogen-activated protein kinase (MAPK)-mediated proinflammatory cytokine induction in host defense mechanisms.

  4. The delay in the development of experimental colitis from isomaltosyloligosaccharides in rats is dependent on the degree of polymerization.

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    Hitoshi Iwaya

    Full Text Available BACKGROUND: Isomaltosyloligosaccharides (IMO and dextran (Dex are hardly digestible in the small intestine and thus influence the luminal environment and affect the maintenance of health. There is wide variation in the degree of polymerization (DP in Dex and IMO (short-sized IMO, S-IMO; long-sized IMO, L-IMO, and the physiological influence of these compounds may be dependent on their DP. METHODOLOGY/PRINCIPAL FINDINGS: Five-week-old male Wistar rats were given a semi-purified diet with or without 30 g/kg diet of the S-IMO (DP = 3.3, L-IMO (DP = 8.4, or Dex (DP = 1230 for two weeks. Dextran sulfate sodium (DSS was administered to the rats for one week to induce experimental colitis. We evaluated the clinical symptoms during the DSS treatment period by scoring the body weight loss, stool consistency, and rectal bleeding. The development of colitis induced by DSS was delayed in the rats fed S-IMO and Dex diets. The DSS treatment promoted an accumulation of neutrophils in the colonic mucosa in the rats fed the control, S-IMO, and L-IMO diets, as assessed by a measurement of myeloperoxidase (MPO activity. In contrast, no increase in MPO activity was observed in the Dex-diet-fed rats even with DSS treatment. Immune cell populations in peripheral blood were also modified by the DP of ingested saccharides. Dietary S-IMO increased the concentration of n-butyric acid in the cecal contents and the levels of glucagon-like peptide-2 in the colonic mucosa. CONCLUSION/SIGNIFICANCE: Our study provided evidence that the physiological effects of α-glucosaccharides on colitis depend on their DP, linkage type, and digestibility.

  5. Ulcerative Colitis

    Science.gov (United States)

    ... or worsen symptoms. Who is more likely to develop ulcerative colitis? Ulcerative colitis can occur in people ... any age. However, it is more likely to develop in people between the ages of 15 and ...

  6. Wheat germ agglutinin anchored chitosan microspheres of reduced brominated derivative of noscapine ameliorated acute inflammation in experimental colitis.

    Science.gov (United States)

    Kaur, Kamalpreet; Sodhi, Rupinder Kaur; Katyal, Anju; Aneja, Ritu; Jain, Upendra Kumar; Katare, Om Prakash; Madan, Jitender

    2015-08-01

    Reduced brominated derivative of noscapine (Red-Br-Nos, EM012), has potent anti-inflammatory property. However, physicochemical limitations of Red-Br-Nos like low aqueous solubility (0.43×10(-3) g/mL), high lipophilicity (logP∼2.94) and ionization at acidic pH greatly encumber the scale-up of oral drug delivery systems for the management of colitis. Therefore, in present investigation, chitosan microspheres bearing Red-Br-Nos (CTS-MS-Red-Br-Nos) were prepared by emulsion polymerization method and later coated with wheat germ agglutinin (WGA-CTS-MS-Red-Br-Nos) to boost the bioadhesive property. The mean particle size and zeta-potential of CTS-MS-Red-Br-Nos were measured to be 10.5±5.4 μm and 8.1±2.2 mV, significantly (P<0.05) lesser than, 30.2±3.2 μm and 19.2±2.3 mV of WGA-CTS-MS-Red-Br-Nos. Furthermore, various spectral techniques like SEM, FT-IR, DSC and PXRD substantiated that Red-Br-Nos was molecularly dispersed in tailored microspheres in amorphous state. Surface bioadhesive property of WGA-CTS-MS-Red-Br-Nos promoted the affinity toward colon mucin cells in simulated colonic fluid (SCF, pH∼7.2). In vitro release studies carried out on WGA-CTS-MS-Red-Br-Nos and CTS-MS-Red-Br-Nos indicated that SCF with colitis milieu (pH∼4.7) favored the controlled release of Red-Br-Nos, owing to solubilization at acidic pH. Consistently, in vivo investigation also demonstrated the utility of WGA-CTS-MS-Red-Br-Nos, which remarkably attenuated the DSS encouraged neutrophil infiltration, myeloperoxidase activity, and pro-inflammatory cytokine production in C57BL6J mice, as compared to CTS-MS-Red-Br-Nos and Red-Br-Nos suspension. The noteworthy anti-inflammatory activity of WGA-CTS-MS-Red-Br-Nos against acute colitis may be attributed to enhanced drug delivery, affinity and utmost drug exposure at inflamed mucosal layers of colon. In conclusion, WGA-CTS-MS-Red-Br-Nos warrants further in-depth in vitro and in vivo investigations to scale-up the technology for clinical

  7. Expression Levels of Proinflammatory Cytokines and NLRP3 Inflammasome in an Experimental Model of Oxazolone-induced Colitis.

    Science.gov (United States)

    Zherebiatiev, Aleksandr; Kamyshnyi, Aleksandr

    2016-02-01

    IL-1β and IL-17A are two cytokines with strong proinflammatory activities and are now known to be involved in a number of chronic inflammatory disorders. High-mobility group box 1 (HMGB1) is a nuclear protein regulating the expression of these proinflammatory cytokines. The NLRP3 inflammasome promotes the maturation of the IL-1β and its activation has been shown as a critical mechanism in the pathogenesis of inflammatory bowel disease (IBD). However, underlying mechanisms to modulate their production in IBD are still unclear. The aim of this study was to investigate the expression levels of mRNA for the NLRP3 inflammasome, HMGB1 and proinflammatory cytokines, IL-1β, IL-17A in the inflamed colon of rats with experimental oxazolone-induced colitis. Experiments were carried out on male wistar rats. IL-1β, IL-17A, HMGB1 and NLRP3 inflammasome mRNA expression were analyzed by real-time reverse transcriptase-polymerase chain reaction. Our results indicated that the expression levels of IL-1β, IL-17A, NLRP3 and HMGB1 were elevated in the inflamed colon of rats with oxazolone-induced colitis.

  8. Beauvericin ameliorates experimental colitis by inhibiting activated T cells via downregulation of the PI3K/Akt signaling pathway.

    Directory of Open Access Journals (Sweden)

    Xue-Feng Wu

    Full Text Available Crohn's disease is a common, chronic inflammatory bowel condition characterized by remission and relapse. Accumulating evidence indicates that activated T cells play an important role in this disease. In the present study, we aimed to examine the effect of beauvericin, a natural cyclic peptide, on 2,4,6-trinitrobenzene sulfonic acid (TNBS-induced colitis in mice, which mimics Crohn's disease. Beauvericin significantly reduced weight loss, diarrhea and mortality, accompanied with notable alleviation of macroscopic and microscopic signs. In addition, this compound decreased serum levels of tumor necrosis factor (TNF-α and interferon (IFN-γ in a concentration-dependent manner in mice with experimental colitis. These effects of beauvericin are attributed to its inhibition on activated T cells. Flow cytometry and immunoblot assay data showed that beauvericin suppressed T-cell proliferation, activation and IFN-γ-STAT1-T-bet signaling and subsequently led to apoptosis of activated T cells by suppressing Bcl-2 and phosphorylated Bad as well as increasing cleavage of caspase-3, -9, -12 and PARP. Furthermore, inhibition of PI3K/Akt signaling, which was an upstream regulator of cell activation and survival in activated T cells, contributed to the effect of beauvericin. Overall, these results supported beauvericin as a novel drug candidate for the treatment of colonic inflammation mainly by targeting PI3K/Akt in activated T cells.

  9. A fusion protein composed of IL-2 and caspase-3 ameliorates the outcome of experimental inflammatory colitis.

    Science.gov (United States)

    Sagiv, Yuval; Kaminitz, Ayelet; Lorberboum-Galski, Haya; Askenasy, Nadir; Yarkoni, Shai

    2009-09-01

    Targeted depletion of immune cells expressing the interleukin-2 (IL-2) receptor can exacerbate inflammatory bowel disease (IBD) through elimination of regulatory T (Treg) cells, or ameliorate its course by depletion of cytotoxic cells. To answer this question we used a fusion protein composed of IL-2 and caspase-3 (IL2-cas) in an experimental model of DSS-induced toxic colitis. In a preventive setting, co-administration of DSS with a daily therapeutic dose of IL2-cas for seven days improved all disease parameters. Although CD4(+)CD25(+) T cells were depleted in the mesenteric lymph nodes, a fractional increase in CD4(+)FoxP3(+) T cells was observed in the spleen. Likewise, IL2-cas therapy improved the outcome of established disease in a chronic model of colitis. These data demonstrate that therapies that use IL-2 as a targeting moiety exert a protective effect over the colon under conditions of inflammation. The efficacy of IL-2-targeted therapy is attributed to reduced activity of reactive T cells, which ameliorates the secondary inflammatory infiltration. IL2-cas evolves as a potential therapeutic tool in IBD.

  10. Anti-inflammatory effects of Lacto-Wolfberry in a mouse model of experimental colitis

    Institute of Scientific and Technical Information of China (English)

    David Philippe; Viral Brahmbhatt; Francis Foata; Yen Saudan; Patrick Serrant; Stephanie Blum; Jalil Benyacoub

    2012-01-01

    AIM:To investigate the anti-inflammatory properties of Lacto-Wolfberry (LWB),both in vitro and using a mouse model of experimental colitis.METHODS:The effects of LWB on lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) and interleukin (IL)-6 secretion were assessed in a murine macrophage cell line.in vitro assessment also included characterizing the effects of LWB on the activation of NF-E2 related 2 pathway and inhibition of tumor necrosis factor-α (TNF-α)-induced nuclear factor-κB (NF-κB) activation,utilizing reporter cell lines.Following the in vitro assessment,the anti-inflammatory efficacy of an oral intervention with LWB was tested in vivo using a preclinical model of intestinal inflammation.Multiple outcomes including body weight,intestinal histology,colonic cytokine levels and anti-oxidative measures were investigated.RESULTS:LWB reduced the LPS-mediated induction of ROS production [+LPS vs 1% LWB + LPS,1590 ±188.5 relative luminescence units (RLU) vs 389 ± 5.9RLU,P < 0.001].LWB was more effective than wolfberry alone in reducing LPS-induced IL-6 secretion in vitro (wolfberry vs 0.5% LWB,15% ± 7.8% vs 64% ±5%,P < 0.001).In addition,LWB increased reporter gene expression via the anti-oxidant response element activation (wolfberry vs LWB,73% ± 6.9% vs 148%± 28.3%,P < 0.001) and inhibited the TNF-α-induced activation of the NF-κB pathway (milk vs LWB,10% ±6.7% vs 35% ± 3.3%,P < 0.05).Furthermore,oral supplementation with LWB resulted in a reduction of macroscopic (-LWB vs +LWB,5.39 ± 0.61 vs 3.66 ±0.59,P =0.0445) and histological scores (-LWB vs +LWB,5.44 ± 0.32 vs 3.66 ± 0.59,P =0.0087) in colitic mice.These effects were associated with a significant decrease in levels of inflammatory cytokines such as IL-1β (-LWB vs +LWB,570 ± 245 μg/L vs 89 ± 38 μg/L,P =0.0106),keratinocyte-derived chemokine/growth regulated protein-α (-LWB vs +LWB,184± 49 μg/L vs 75 ± 20 μg/L,P =0.0244),IL-6 (-LWB

  11. Effects of Rhizophora mangle on Experimental Colitis Induced by TNBS in Rats.

    Science.gov (United States)

    de Faria, Felipe Meira; Luiz-Ferreira, Anderson; Socca, Eduardo Augusto Rabelo; de Almeida, Ana Cristina Alves; Dunder, Ricardo José; Manzo, Luis Paulo; da Silva, Marcelo Aparecido; Vilegas, Wagner; Rozza, Ariane Leite; Pellizzon, Cláudia Helena; Dos Santos, Lourdes Campaner; Souza Brito, Alba Regina Monteiro

    2012-01-01

    Male Unib-WH rats were pretreated for two weeks with butanolic (BuOH) and ethyl acetate (EtOAc) fractions. Colitis was induced by rectal administration of TNBS, the treatment continued, and animals were sacrificed on day 7 after the TNBS administration. Phytochemical studies were performed in order to provide the characterization of the tannins present in the bark of R. mangle. Results showed that EtOAc fraction increased the levels of IL-10 (∗∗P induced by TNBS through different mechanisms, probably by their chemical composition which directed its activity into an antioxidant or anti-inflammatory response, leading to an immune modulation.

  12. Faecalibacterium prausnitzii Strain HTF-F and Its Extracellular Polymeric Matrix Attenuate Clinical Parameters in DSS-Induced Colitis.

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    Oriana Rossi

    Full Text Available A decrease in the abundance and biodiversity of intestinal bacteria within the Firmicutes phylum has been associated with inflammatory bowel disease (IBD. In particular, the anti-inflammatory bacterium Faecalibacterium prausnitzii, member of the Firmicutes phylum and one of the most abundant species in healthy human colon, is underrepresented in the microbiota of IBD patients. The aim of this study was to investigate the immunomodulatory properties of F. prausnitzii strain A2-165, the biofilm forming strain HTF-F and the extracellular polymeric matrix (EPM isolated from strain HTF-F. For this purpose, the immunomodulatory properties of the F. prausnitzii strains and the EPM were studied in vitro using human monocyte-derived dendritic cells. Then, the capacity of the F. prausnitzii strains and the EPM of HTF-F to suppress inflammation was assessed in vivo in the mouse dextran sodium sulphate (DSS colitis model. The F. prausnitzii strains and the EPM had anti-inflammatory effects on the clinical parameters measured in the DSS model but with different efficacy. The immunomodulatory effects of the EPM were mediated through the TLR2-dependent modulation of IL-12 and IL-10 cytokine production in antigen presenting cells, suggesting that it contributes to the anti-inflammatory potency of F. prausnitzii HTF-F. The results show that F. prausnitzii HTF-F and its EPM may have a therapeutic use in IBD.

  13. Induction of experimental acute ulcerative colitis in rats by administration of dextran sulfate sodium at low concentration followed by intracolonic administration of 30% ethanol

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Several models of experimental ulcerative colitis have been reported previously. However, none of these models showed the optimum characteristics. Although dextran sulfate sodium-induced colitis results in inflammation resembling ulcerative colitis, an obvious obstacle is that dextran sulfate sodium is very expensive. The aim of this study was to develop an inexpensive model of colitis in rats. Sprague-Dawley rats were treated with 2% dextran sulfate sodium in drinking water for 3 d followed by an intracolonic administration of 30% ethanol. The administration of 2% dextran sulfate sodium followed by 30% ethanol induced significant weight loss, diarrhea and hematochezia in rats. Severe ulceration and inflammation of the distal part of rat colon were developed rapidly. Histological examination showed increased infiltration of polymorphonuclear leukocytes,lymphocytes and existence of cryptic abscesses and dysplasia. The model induced by dextran sulfate sodium at lower concentration followed by 30% ethanol is characterized by a clinical course, localization of the lesions and histopathological features similar to human ulcerative colitis and fulfills the criteria set out at the beginning of this study.

  14. Ethanol Extract of Cordyceps militaris Grown on Germinated Soybeans Attenuates Dextran-Sodium-Sulfate- (DSS-) Induced Colitis by Suppressing the Expression of Matrix Metalloproteinases and Inflammatory Mediators

    Science.gov (United States)

    Park, Dong Ki; Park, Hye-Jin

    2013-01-01

    The effect of Cordyceps militaris (CM) grown on germinated soybeans (GSC) in the inflammatory bowel disease (IBD) model was studied. To demonstrate the preventive effect of GSC extract in a dextran-sodium-sulfate- (DSS-) induced acute colitis mouse model, GSC was administered 2 days before DSS coadministration. GSC significantly suppressed DSS-induced disease activity index (DAI) as well as histopathological scores, compared to control or CM-treated group. To elucidate the anti-IBD activity of GSC, we checked the level of matrix metalloproteinases (MMPs) and inflammatory mediators. GSC extract decreased the level of MMP-3 and -9 mRNAs and p53 proteins. The level and activity of LPS-induced MMP-9 were reduced in GSC-treated RAW264.7 cells. It also attenuated the level of inducible nitric oxide synthase (iNOS) and tumor necrosis factor- (TNF-) α mRNAs both in colon tissue and in macrophage cells. These results suggest that GSC can be applied as a protective agent against IBDs. PMID:23841050

  15. Ethanol Extract of Cordyceps militaris Grown on Germinated Soybeans Attenuates Dextran-Sodium-Sulfate- (DSS- Induced Colitis by Suppressing the Expression of Matrix Metalloproteinases and Inflammatory Mediators

    Directory of Open Access Journals (Sweden)

    Dong Ki Park

    2013-01-01

    Full Text Available The effect of Cordyceps militaris (CM grown on germinated soybeans (GSC in the inflammatory bowel disease (IBD model was studied. To demonstrate the preventive effect of GSC extract in a dextran-sodium-sulfate- (DSS- induced acute colitis mouse model, GSC was administered 2 days before DSS coadministration. GSC significantly suppressed DSS-induced disease activity index (DAI as well as histopathological scores, compared to control or CM-treated group. To elucidate the anti-IBD activity of GSC, we checked the level of matrix metalloproteinases (MMPs and inflammatory mediators. GSC extract decreased the level of MMP-3 and -9 mRNAs and p53 proteins. The level and activity of LPS-induced MMP-9 were reduced in GSC-treated RAW264.7 cells. It also attenuated the level of inducible nitric oxide synthase (iNOS and tumor necrosis factor- (TNF- α mRNAs both in colon tissue and in macrophage cells. These results suggest that GSC can be applied as a protective agent against IBDs.

  16. Activation of aryl hydrocarbon receptor (AhR leads to reciprocal epigenetic regulation of FoxP3 and IL-17 expression and amelioration of experimental colitis.

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    Narendra P Singh

    Full Text Available BACKGROUND: Aryl hydrocarbon receptor (AhR, a transcription factor of the bHLH/PAS family, is well characterized to regulate the biochemical and toxic effects of environmental chemicals. More recently, AhR activation has been shown to regulate the differentiation of Foxp3(+ Tregs as well as Th17 cells. However, the precise mechanisms are unclear. In the current study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AhR ligand, on epigenetic regulation leading to altered Treg/Th17 differentiation, and consequent suppression of colitis. METHODOLOGY/PRINCIPAL FINDINGS: Dextran sodium sulphate (DSS administration induced acute colitis in C57BL/6 mice, as shown by significant weight loss, shortening of colon, mucosal ulceration, and increased presence of CXCR3(+ T cells as well as inflammatory cytokines. Interestingly, a single dose of TCDD (25 µg/kg body weight was able to attenuate all of the clinical and inflammatory markers of colitis. Analysis of T cells in the lamina propria (LP and mesenteric lymph nodes (MLN, during colitis, revealed decreased presence of Tregs and increased induction of Th17 cells, which was reversed following TCDD treatment. Activation of T cells from AhR(+/+ but not AhR (-/- mice, in the presence of TCDD, promoted increased differentiation of Tregs while inhibiting Th17 cells. Analysis of MLN or LP cells during colitis revealed increased methylation of CpG islands of Foxp3 and demethylation of IL-17 promoters, which was reversed following TCDD treatment. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate for the first time that AhR activation promotes epigenetic regulation thereby influencing reciprocal differentiation of Tregs and Th17 cells, and amelioration of inflammation.

  17. B cells exposed to enterobacterial components suppress development of experimental colitis

    DEFF Research Database (Denmark)

    Schmidt, Esben Gjerløff Wedebye; Larsen, Hjalte List; Kristensen, Nanna Ny

    2012-01-01

    BACKGROUND: B cells positively contribute to immunity by antigen presentation to CD4(+) T cells, cytokine production, and differentiation into antibody secreting plasma cells. Accumulating evidence implies that B cells also possess immunoregulatory functions closely linked to their capability of IL......-10 secretion. METHODS: Colitis development was followed in CD4(+) CD25(-) T cell transplanted SCID mice co-transferred with B cells exposed to an enterobacterial extract (ebx-B cells). B and T cell cytokine expression was measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA......). RESULTS: We demonstrate that splenic B cells exposed to ebx produce large amounts of IL-10 in vitro and express CD1d and CD5 previously known to be associated with regulatory B cells. In SCID mice transplanted with colitogenic CD4(+) CD25(-) T cells, co-transfer of ebx-B cells significantly suppressed...

  18. Polyphenol extract from evening primrose pomace alleviates experimental colitis after intracolonic and oral administration in mice.

    Science.gov (United States)

    Sałaga, M; Lewandowska, U; Sosnowska, D; Zakrzewski, P K; Cygankiewicz, A I; Piechota-Polańczyk, A; Sobczak, M; Mosinska, P; Chen, Chunqiu; Krajewska, W M; Fichna, J

    2014-11-01

    Oenothera paradoxa (EP) preparations are commonly used in folk medicine to treat skin diseases, neuralgia, and gastrointestinal (GI) disorders. Several reports suggested that EP preparations exhibit potent anti-inflammatory and antioxidant activities both in vitro and in vivo. Here, we aimed to characterize the action of EP pomace polyphenol extract in mouse model of colitis. We analyzed the composition of EP pomace polyphenol extract using reversed phase HPLC system and ultra-performance liquid chromatography (UPLC) system coupled with a quadrupole-time of flight (Q-TOF) MS instrument. Then, we used a well-established animal model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis to determine the anti-inflammatory action of EP pomace polyphenol extract. We also investigated the effect of the EP pomace polyphenol extract on pro-inflammatory (IL-1β and TNF-α) cytokine mRNA levels and hydrogen peroxide concentration in the inflamed colon. Administration of EP pomace polyphenol extract significantly improved macroscopic and microscopic damage scores, as well as myeloperoxidase (MPO) activity in TNBS-treated mice. The anti-inflammatory effect of the extract was observed after intracolonic and oral administration and was dose-dependent. Significant reduction of tissue hydrogen peroxide level after treatment with EP pomace polyphenol extract suggests that its therapeutic effect is a result of free radical scavenging. This novel finding indicates that the application of the EP pomace polyphenol extract in patients with inflammatory bowel diseases (IBDs) may become an attractive supplementary treatment for conventional anti-inflammatory therapy.

  19. Gingko biloba extract (Ginaton) ameliorates dextran sulfate sodium (DSS)-induced acute experimental colitis in mice via reducing IL-6/STAT3 and IL-23/IL-17.

    Science.gov (United States)

    Sun, Yan; Lin, Lian-Jie; Lin, Yan; Sang, Li-Xuan; Jiang, Min; Zheng, Chang-Qing

    2015-01-01

    This study explored the underlying mechanism of Gingko biloba extract (Ginaton) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice. 40 male C57BL/6 mice were randomly divided into four groups: normal control group, Ginaton group, Ginaton treatment group, and DSS group. After 7 days administration, mice were sacrificed and colons were collected for H-E staining, immunohistochemistry, real-time PCR and Western blot. By observing clinical disease activity and histological damage, we assessed the effect of Ginaton on DSS-induced acute experimental colitis in mice and observed the effect of Ginaton on normal mice. We also explored the specific mechanism of Ginaton on DSS-induced acute experimental colitis in mice through examining the expression of inflammatory related mediators (gp130, STAT3, p-STAT3, ROR-γt) and cytokines (IL-6, IL-17, IL-23). Ginaton-treated DSS mice showed significant improvement over untreated DSS mice. Specifically, Ginaton improved clinical disease activity (DAI score, weight closs, colon shortening, and bloody stool) and histological damage, and reduced the expression of inflammatory-related mediators (p-STAT3, gp130, ROR-γt) and cytokines (IL-6, IL-17, IL-23). In addition, clinical disease activity, histological damage, the expression of inflammatory related mediators (STAT3, p-STAT3, gp130, ROR-t) and cytokines (IL-6, IL-17, IL-23) in mice of Ginaton group were similar to normal control group. In conclusion, Ginaton ameliorates DSS-induced acute experimental colitis in mice by reducing IL-17 production, which is at least partly involved in inhibiting IL-6/STAT3 signaling pathway and IL-23/IL-17 axis. Moreover, Ginaton itself does not cause inflammatory change in normal mice. These results support that Ginaton can be as a potential clinical treatment for ulcerative colitis (UC).

  20. Efficacy of oral administration of lactic acid bacteria isolated from cocoa in a fermented milk preparation: reduction of colitis in an experimental rat model.

    Science.gov (United States)

    Dos Santos, T F; Melo, T A; Santos, D S; Rezende, R P; Dias, J C T; Romano, C C

    2016-07-29

    We investigated the probiotic potential of lactic acid bacteria (LAB) obtained from cocoa fermentation using an experimental rat model of colitis. Cocoa beans were collected from fermentation boxes every 12 h for 5 days to isolate the microorganisms. Strains were isolated by serial dilution and plating on MRS agar. Gram-positive and catalase-negative rods were subjected to DNA extraction, polymerase chain reaction, and sequencing. Ten strains were randomly pooled and used to prepare a fermented milk drink that was used to treat the experimental colitis. A parallel group was treated with a single strain drink. Serum concentrations of cytokines and IgA, total and differential counts of blood leukocytes, and histological appearance were compared with the untreated control colitis group. Eighty strains of LAB were identified as Lactobacillus fermentum (68) and Lactobacillus plantarum (12). The multi-strain LAB pool significantly reduced the total number of leukocytes. There was a significant reduction in the percentage of neutrophils and monocytes compared with the control colitis group. IFN-γ concentration was downregulated in animals treated with the LAB pool. IL-10 and IgA increased significantly in the group treated with the strains. Histological analysis showed that the LAB pool reduced the inflammatory infiltrate and restored tissue architecture. The group treated with the single strain LAB drink (L. fermentum) showed no signs of inflammation remission. The results confirm the probiotic action of cocoa-derived LAB in the treatment of experimental colitis. Studies using isogenic models and humans will clarify the mechanisms of immune response modulation in inflammatory bowel disease.

  1. An experimental model of ice floe induced attenuation of ocean waves

    CERN Document Server

    Toffoli, Alessandro; Bennetts, Luke G; Meylan, Michael H; Cavaliere, Claudio; Babanin, Alexandr

    2014-01-01

    An experimental model of ocean wave attenuation due to interactions with an ice floe is presented. Evolution of mechanically-generated, regular waves is monitored in front and in the lee of a solitary, square floe, made of a synthetic material. Results confirm dependence of attenuation on the period of the incident wave. Results also indicate dependence of attenuation on the depth of wave overwash on the floe.

  2. Immune-protective effect of echinococcosis on colitis experimental model is dependent of down regulation of TNF-α and NO production.

    Science.gov (United States)

    Khelifi, Lila; Soufli, Imene; Labsi, Moussa; Touil-Boukoffa, Chafia

    2017-02-01

    Hydatid disease (echinococcosis) is a chronic, endemic helminthic disease caused by the larval stage of the tapeworm, Echinococcus granulosus. This disease is endemic in many parts of the world, such as the Mediterranean area, and in particular in Algeria. Helminth parasites have developed complex strategies to modulate the immune responses of their hosts through versatile immune-regulatory mechanisms. These mechanisms may regulate immune responses associated with inflammatory diseases such as inflammatory bowel diseases (IBD). the goal of this study was to investigate the effect of Echinococcus granulosus infection on the development of dextran sulfate sodium (DSS)-induced colitis. Our results demonstrated that E. granulosus infection significantly improved the clinical symptoms and histological scores observed during DSS-induced colitis, and also maintained mucus production by goblet cells. Interestingly, this infection reduced Nitric oxide (NO) and tumor necrosis factor α (TNF-α) production and attenuated inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) expression in colonic tissues. Collectively, our data support the hygiene hypothesis and indicate that prior infection with E. granulosus can effectively protect mice from DSS-induced colitis by enhancing immune-regulatory mechanisms.

  3. Effects of Rhizophora mangle on Experimental Colitis Induced by TNBS in Rats

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    Felipe Meira de Faria

    2012-01-01

    Full Text Available Male Unib-WH rats were pretreated for two weeks with butanolic (BuOH and ethyl acetate (EtOAc fractions. Colitis was induced by rectal administration of TNBS, the treatment continued, and animals were sacrificed on day 7 after the TNBS administration. Phytochemical studies were performed in order to provide the characterization of the tannins present in the bark of R. mangle. Results showed that EtOAc fraction increased the levels of IL-10 (**P<0.01 and diminished the levels of TNF-α (***P<0.001 and IL-6 (**P<0.01. BuOH fraction reduced the MPO activity (**P<0.01 and levels of TBARS (***P<0.001; it also increased COX-1 expression, diminished the levels of TNF-α (***P<0.001, and increased the levels of IL-12 (***P<0.001. Besides, both treatments augmented the levels of GSH (*P<0.05, the activity of GSH-Px (**P<0.01 for BuOH fraction and ***P<0.001 for EtOAc fraction, and CAT (**P<0.01. In conclusion, both treatments ameliorated the injury induced by TNBS through different mechanisms, probably by their chemical composition which directed its activity into an antioxidant or anti-inflammatory response, leading to an immune modulation.

  4. Ulcerative colitis - discharge

    Science.gov (United States)

    Inflammatory bowel disease - ulcerative colitis - discharge; Ulcerative proctitis - discharge; Colitis - discharge ... were in the hospital because you have ulcerative colitis. This is a swelling of the inner lining ...

  5. Oral Grapeseed Oil and Sesame Oil in Experimental Acetic Acid-Induced Ulcerative Colitis in Rat

    Directory of Open Access Journals (Sweden)

    Hosseinzadeh

    2016-06-01

    Full Text Available Background Ulcerative colitis (UC is a multi-factorial disease with unknown etiology and has many clinical manifestations. Objectives The current study aimed to evaluate the effects of sesame oil (SO and grapeseed oil (GSO on acetic acid-induced UC in rats. Materials and Methods Eighty male rats were divided into eight groups as health control (HC1, received normal saline; HC2, received SO; HC3, received GSO; negative control (NC, UC and normal saline; positive control (PC, UC and mesalamine; SO, UC and SO; GSO, UC and GSO, and SO + GSO. The daily weight changes, serum levels of oxidative stress markers and lipid profile plus colon macroscopic and microscopic histological changes were measured at the end of the seventh day. Results Significant differences were detected between HC1 and PC on the 3rd (P = 0.002, 4th (0.013 and 6th days (0.014 and between HC1 and NC on the 4th day (0.027 in weight of rats. Use of GSO alone or in combination with SO decreased the extent of the changes both in macroscopic and microscopic indices and also at the inflammation level. The most significant decrease in the MDA level and the most obvious increase in the TAC belonged to the GSO group in comparison to the NC group. The lowest cholesterol (51.43 ± 5.62 mg/dL and HDL levels (29.29 ± 6.24 mg/dL were detected in response to SO consumption in comparison to NC group (P = 0.030 and P = 0.257, respectively. Conclusions GSO in combination with SO may be considered as the treatment of choice for UC based on antioxidant and histopathological evaluations.

  6. Luminal and parenteral TFF2 and TFF3 dimer and monomer in two models of experimental colitis in the rat

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Kissow, Hannelouise; Hare, Kristine;

    2005-01-01

    % dextran sodium sulphate in the drinking water or by one intraperitoneal injection of mitomycin C, 3.75 mg/kg. TFF peptides were administered as subcutaneous injections or directly into the lumen via a catheter placed in the proximal colon. Treatments were saline, TFF2, TFF3 monomer or TFF3 dimer 5 mg....../kg twice per day throughout the study [dextran sulphate sodium (DSS)] or from day 4 to 7 (mitomycin C). Colitis severity was scored in a stereomicroscope and histologically. RESULTS: Luminal treatment with TFF3 in its dimeric form significantly improved the colitis score in both colitis models, whereas TFF...

  7. Anti-inflammatory effect of cannabinoid agonist WIN55, 212 on mouse experimental colitis is related to inhibition of p38MAPK

    Science.gov (United States)

    Feng, Ya-Jing; Li, Yong-Yu; Lin, Xu-Hong; Li, Kun; Cao, Ming-Hua

    2016-01-01

    AIM To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid (CB) receptors, WIN55-212-2 (WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future. METHODS We established the colitis model in C57BL/6 mice by replacing the animals’ water supply with 4% dextran sulfate sodium (DSS) for 7 consecutive days. A colitis scoring system was used to evaluate the severity of colon local lesion. The plasma levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the myeloperoxidase (MPO) activity in colon tissue were measured. The expressions of cannabinoid receptors, claudin-1 protein, p38 mitogen-activated protein kinase (p38MAPK) and its phosphorylated form (p-p38) in colon tissue were determined by immunohistochemistry and Western blot. In addition, the effect of SB203580 (SB), an inhibitor of p38, was investigated in parallel experiments, and the data were compared with those from intervention groups of WIN55 and SB alone or used together. RESULTS The results demonstrated that WIN55 or SB treatment alone or together improved the pathological changes in mice with DSS colitis, decreased the plasma levels of TNF-α, and IL-6, and MPO activity in colon. The enhanced expression of claudin-1 and the inhibited expression of p-p38 in colon tissues were found in the WIN55-treated group. Besides, the expression of CB1 and CB2 receptors was enhanced in the colon after the induction of DSS colitis, but reduced when p38MAPK was inhibited. CONCLUSION These results confirmed the anti-inflammatory effect and protective role of WIN55 on the mice with experimental colitis, and revealed that this agent exercises its action at least partially by inhibiting p38MAPK. Furthermore, the results showed that SB203580, affected the expression of CB1 and CB2 receptors in the mouse colon, suggesting a close linkage and cross-talk between the p38

  8. Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis

    Institute of Scientific and Technical Information of China (English)

    Kunwar; Shailubhai; Vaseem; Palejwala; Krishna; Priya; Arjunan; Sayali; Saykhedkar; Bradley; Nefsky; John; A; Foss; Stephen; Comiskey; Gary; S; Jacob; Scott; E; Plevy

    2015-01-01

    AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first

  9. Types of Ulcerative Colitis

    Science.gov (United States)

    ... Colitis? > Types of Ulcerative Colitis Types of Ulcerative Colitis Email Print + Share If you are diagnosed with ... abdomen may occur in active disease. Left-sided Colitis Continuous inflammation that begins at the rectum and ...

  10. Microscopic colitis

    DEFF Research Database (Denmark)

    Münch, A; Aust, D; Bohr, Jakob

    2012-01-01

    Microscopic colitis (MC) is an inflammatory bowel disease presenting with chronic, non-bloody watery diarrhoea and few or no endoscopic abnormalities. The histological examination reveals mainly two subtypes of MC, lymphocytic or collagenous colitis. Despite the fact that the incidence in MC has...... been rising over the last decades, research has been sparse and our knowledge about MC remains limited. Specialists in the field have initiated the European Microscopic Colitis Group (EMCG) with the primary goal to create awareness on MC. The EMCG is furthermore a forum with the intention to promote...

  11. Short-chain inulin-like fructans reduce endotoxin and bacterial translocations and attenuate development of TNBS-induced colitis in rats.

    Science.gov (United States)

    Ito, Hiroyuki; Tanabe, Hiroki; Kawagishi, Hirokazu; Tadashi, Wada; Yasuhiko, Tomono; Sugiyama, Kimio; Kiriyama, Shuhachi; Morita, Tatsuya

    2009-10-01

    Anti-inflammatory effects of short-chain inulin-like fructans (SCF) on trinitrobenzene sulfonic acid (TNBS)-induced colitis were investigated in rats, focusing specifically on endotoxin and bacterial translocations. SCF with degrees of polymerization (DP) of 4 and 8 were used. Rats were fed either control diet or diets including 60 g DP4 or DP8 per kilogram for 7 days, and then received intracolonic TNBS and were fed the respective diets for a further 10 days. DP4 and DP8 significantly reduced colonic injuries as assessed by damage score, but the reduction of colonic myeloperoxidase activity was manifest solely with DP8. At 3 days after colitis induction, bacterial translocation to the mesenteric lymph node was significantly lower in the DP4 and DP8 groups, but significant reduction in the portal endotoxin concentration was achieved solely in the DP8 group. Immediately prior to colitis induction, cecal immunoglobulin A and mucin concentrations were higher in the DP4 and DP8 groups, but these changes were abolished at 10 days post colitis induction. The data suggest that SCF exert prophylactic effects against TNBS colitis, presumably as a result of inhibitory effects on endotoxin and bacterial translocations.

  12. [Collagenous colitis].

    Science.gov (United States)

    Lindström, C G

    1991-05-01

    Collagenous colitis is now regarded by an overwhelming majority of authors as a clinicopathological entity and has been taken up as a such in many text-books and diagnostic atlases (Morson & Dawson, 1990, Fenoglio-Preiser et al., 1989, Whitehead 1985, Whitehead 1989). A good, detailed review of cases of collagenous colitis published up to 1988 was performed by Perri et al. Collagenous colitis was also presented to a wider medical public through a clinicopathological conference case at Massachusetts General Hospital (Case 29-1988). Finally it may be added that collagenous colitis has been included in the new fourth edition of Robbins Pathologic Basis of Disease (Cotran, Kumar, Robbins, 1989), where the possibility of an autoimmune disease is stressed.

  13. Pseudomembranous Colitis

    OpenAIRE

    2015-01-01

    Pseudomembranous colitis is an inflammatory condition of the colon characterized by elevated yellow-white plaques that coalesce to form pseudomembranes on the mucosa. Patients with the condition commonly present with abdominal pain, diarrhea, fever, and leukocytosis. Because pseudomembranous colitis is often associated with C. difficile infection, stool testing and empiric antibiotic treatment should be initiated when suspected. When results of C. difficile testing are negative and symptoms p...

  14. Microscopic colitis

    Institute of Scientific and Technical Information of China (English)

    Gianluca Ianiro; Giovanni Cammarota; Luca Valerio; Brigida Eleonora Annicchiarico; Alessandro Milani; Massimo Siciliano; Antonio Gasbarrini

    2012-01-01

    Microscopic colitis may be defined as a clinical syndrome,of unknown etiology,consisting of chronic watery diarrhea,with no alterations in the large bowel at the endoscopic and radiologic evaluation.Therefore,a definitive diagnosis is only possible by histological analysis.The epidemiological impact of this disease has become increasingly clear in the last years,with most data coming from Western countries.Microscopic colitis includes two histological subtypes [collagenous colitis (CC) and lymphocytic colitis (LC)] with no differences in clinical presentation and management.Collagenous colitis is characterized by a thickening of the subepithelial collagen layer that is absent in LC.The main feature of LC is an increase of the density of intra-epitll lial lymphocytes in the surface epithelium.A number of pathogenetic theories have been proposed over the years,involving the role of luminal agents,autoimmunity,eosinophils,genetics (human leukocyte antigen),biliary acids,infections,alterations of pericryptal fibroblasts,and drug intake; drugs like ticlopidine,carbamazepine or ranitidine are especially associated with the development of LC,while CC is more frequently linked to cimetidine,non-steroidal antiinflammatory drugs and lansoprazole.Microscopic colitis typically presents as chronic or intermittent watery diarrhea,that may be accompanied by symptoms such as abdominal pain,weight loss and incontinence.Recent evidence has added new pharmacological options for the treatment of microscopic colitis:the role of steroidal therapy,especially oral budesonide,has gained relevance,as well as immunosuppressive agents such as azathioprine and 6-mercaptopurine.The use of anti-tumor necrosis factor-α agents,infliximab and adalimumab,constitutes a new,interesting tool for the treatment of microscopic colitis,but larger,adequately designed studies are needed to confirm existing data.

  15. Conventional housing conditions attenuate the development of experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Andreas Arndt

    Full Text Available BACKGROUND: The etiology of multiple sclerosis (MS has remained unclear, but a causative contribution of factors outside the central nervous system (CNS is conceivable. It was recently suggested that gut bacteria trigger the activation of CNS-reactive T cells and the development of demyelinative disease. METHODS: C57BL/6 (B6 mice were kept either under specific pathogen free or conventional housing conditions, immunized with the myelin basic protein (MBP-proteolipid protein (PLP fusion protein MP4 and the development of EAE was clinically monitored. The germinal center size of the Peyer's patches was determined by immunohistochemistry in addition to the level of total IgG secretion which was assessed by ELISPOT. ELISPOT assays were also used to measure MP4-specific T cell and B cell responses in the Peyer's patches and the spleen. Ear swelling assays were performed to determine the extent of delayed-type hypersensitivity reactions in specific pathogen free and conventionally housed mice. RESULTS: In B6 mice that were actively immunized with MP4 and kept under conventional housing conditions clinical disease was significantly attenuated compared to specific pathogen free mice. Conventionally housed mice displayed increased levels of IgG secretion in the Peyer's patches, while the germinal center formation in the gut and the MP4-specific TH17 response in the spleen were diminished after immunization. Accordingly, these mice displayed an attenuated delayed type hypersensitivity (DTH reaction in ear swelling assays. CONCLUSIONS: The data corroborate the notion that housing conditions play a substantial role in the induction of murine EAE and suggest that the presence of gut bacteria might be associated with a decreased immune response to antigens of lower affinity. This concept could be of importance for MS and calls for caution when considering the therapeutic approach to treat patients with antibiotics.

  16. Bifidobacterium infantis strains with and without a combination of Oligofructose and Inulin (OFI attenuate inflammation in DSS-induced colitis in rats

    Directory of Open Access Journals (Sweden)

    Ahrne Siv

    2006-10-01

    Full Text Available Abstract Background Pathogenesis of inflammatory bowel disease is thought to be through different factors and there is a relationship between the gut flora and the risk of its development. Probiotics can manipulate the microflora in chronic inflammation and may be effective in treating inflammation. Bifidobacterium are saccharolytic and their growth in the gut can be promoted by non-absorbable carbohydrates and its increase in the colon appears to be of benefit. Methods Oligofructose and inulin (OFI alone and the two B. infantis DSM 15158 and DSM 15159 with and without OFI, were fed to Sprague-Dawley rats for 7 days prior to colitis induction and administrations continued for another 7 days with the DSS. Colitis severity assessed using a Disease Activity Index. Samples were collected 7 days after colitis induction, for intestinal bacterial flora, bacterial translocation, short chain fatty acids (SCFAs, myeloperoxidase (MPO, cytokines (IL-1β, TNF-α, IL-10 and TGF-β and malondialdehyde (MDA. Results OFI alone or the B. infantis strains with and without OFI improved significantly the DAI and decreased colonic MPO activity. Colonic tissue IL-1β decreased significantly in all treated groups except B. infantis DSM 15158. MDA decreased significantly in B. infantis DSM 15159 with and without OFI compared to colitis control. Succinic acid increased significantly in OFI group with and without DSM 15159 compared to all groups. Sum values of propionic, succinic acid and butyric acid increased significantly in all groups compare to the colitis control. Bacterial translocation to mesenteric lymph nodes decreased significantly in all groups compared to colitis control. Translocation to the liver decreased significantly in all groups compare to the colitis control and OFI + B. infantis DSM 15158 groups. Conclusion Administrations of OFI and Bifidobacterium improve DSS-induced acute colitis and have an anti-inflammatory effect. Major differences in effect

  17. Prevention of Chronic Experimental Colitis Induced by Dextran Sulphate Sodium (DSS in Mice Treated with FR91

    Directory of Open Access Journals (Sweden)

    Valter R. M. Lombardi

    2012-01-01

    Full Text Available One of the main treatments currently used in humans to fight cancer is chemotherapy. A huge number of compounds with antitumor activity are present in nature, and many of their derivatives are produced by microorganisms. However, the search for new drugs still represents a main objective for cancer therapy, due to drug toxicity and resistance to multiple chemotherapeutic drugs. In animal models, a short-time oral administration of dextran sulfate sodium (DSS induces colitis, which exhibits several clinical and histological features similar to ulcerative colitis (UC. However, the pathogenic factors responsible for DSS-induced colitis and the subsequent colon cancer also remain unclear. We investigated the effect of FR91, a standardized lysate of microbial cells belonging to the Bacillus genus which has been previously shown to have significant immunomodulatory effects, against intestinal inflammation. Colitis was induced in mice during 5 weeks by oral administration 2% (DSS. Morphological changes in the colonic mucosa were evaluated by hematoxylin-eosin staining and immunohistochemistry methods. Adenocarcinoma and cryptal cells of the dysplastic epithelium showed cathenin-β, MLH1, APC, and p53 expression, together with increased production of IFN-γ. In our model, the optimal dose response was the 20% FR91 concentration, where no histological alterations or mild DSS-induced lesions were observed. These results indicate that FR91 may act as a chemopreventive agent against inflammation in mice DSS-induced colitis.

  18. Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles

    Directory of Open Access Journals (Sweden)

    Naeem M

    2015-07-01

    Full Text Available Muhammad Naeem, Jiafu Cao, Moonjeong Choi, Woo Seong Kim, Hyung Ryong Moon, Bok Luel Lee, Min-Soo Kim, Yunjin Jung, Jin-Wook Yoo College of Pharmacy, Pusan National University, Busan, South Korea Abstract: Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy. Keywords: azo-polyurethane, methacrylate copolymer, budesonide, colon-targeted nanoparticles, colitis

  19. Experimental and Pathalogical study of Pistacia atlantica, butyrate, Lactobacillus casei and their combination on rat ulcerative colitis model.

    Science.gov (United States)

    Gholami, Mahdi; Ghasemi-Niri, Seyedeh Farnaz; Maqbool, Faheem; Baeeri, Maryam; Memariani, Zahra; Pousti, Iraj; Abdollahi, Mohammad

    2016-06-01

    This study evaluated the effects of Pistacia atlantica (P. atlantica), butyrate, Lactobacillus casei (L. casei) and especially their combination therapy on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced rat colitis model. Rats were divided into seven groups. Four groups received oral P. atlantica, butyrate, L. casei and the combination of three agents for 10 consecutive days. The remaining groups were negative and positive controls and a sham group. Macroscopic and histopathological examinations were carried out along with determination of the specific biomarker of colonic oxidative stress, the myeloperoxidase (MPO). Compared with controls, the combination therapy exhibited a significant alleviation of colitis in terms of pathological scores and reduction of MPO activity (55%, p=0.0009). Meanwhile, the macroscopic appearance such as stool consistency, tissue and histopathological scores (edema, necrosis and neutrophil infiltration) were improved. Although single therapy by each P. atlantica, butyrate, and L. casei was partially beneficial in reduction of colon oxidative stress markers, the combination therapy was much more effective. In conclusion, the combination therapy was able to reduce the severity of colitis that is clear from biochemical markers. Future studies have to focus on clinical effects of this combination in management of human ulcerative colitis. Further molecular and signaling pathway studies will help to understand the mechanisms involved in the treatment of colitis and inflammatory diseases.

  20. Sleep deprivation attenuates experimental stroke severity in rats

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Constantinescu, Alexandra Oana; Balseanu, Adrian

    2010-01-01

    Indirect epidemiological and experimental evidence suggest that the severity of injury during stroke is influenced by prior sleep history. The aim of our study was to test the effect of acute sleep deprivation on early outcome following experimental stroke. Young male Sprague-Dawley rats (n=20......) were subjected to focal cerebral ischemia by reversible right middle cerebral artery occlusion (MCAO) for 90 min. In 10 rats, MCAO was performed just after 6-h of total sleep deprivation (TSD) by "gentle handling", whereas the other rats served as controls. Neurological function during the first week...

  1. Role of commensal bacteria in chronic experimental colitis: lessons from the HLA-B27 transgenic rat.

    Science.gov (United States)

    Rath, Heiko C

    Rats on Lewis or Fischer background, transgenic for human HLA-B27 and beta(2)-microglobulin genes spontaneously develop colitis, gastritis, arthritis, dermatitis, orchitis, epididymitis, carditis, alopecia and nail changes. Disease susceptibility correlates with the gene copy number and is influenced by the genetic background. The pathomechanism in this model is still not completely understood. Cell transfer experiments indicate an essential role of HLA-B27 expression in bone marrow-derived cells. On Fischer background the onset of colitis occurs at 2 months of age, peaks at 3 months of age, and plateaus. Histologic findings include inflammatory cell infiltration, mostly limited to the mucosa, crypt hyperplasia, reduction of goblet cells, occasionally crypt abscesses and early ulcers. There is evidence that normal luminal bacteria play an essential role in initiating and perpetuating chronic colitis and gastritis in HLA-B27 transgenic rats: Transgenic rats raised under germ-free conditions do not develop gastrointestinal disease, whereas transgenic littermates exposed to specific pathogen-free bacteria develop colitis and gastritis within 2-4 weeks. Obligate anaerobic bacteria, especially Bacteroides spp., may play a predominant role since metronidazole prevents colitis and transgenic germ-free rats contaminated with a cocktail of six obligate and facultative anaerobic bacteria develop colitis and gastritis only in the presence of Bacteroides vulgatus. Luminal bacteria may also be involved in trafficking and homing of inflammatory cells into remote organs, since varying cecal bacterial composition does not only alter local inflammation but also influences gastritis. Lymphocyte transfer experiments indicate a specific response to luminal bacteria. In summary, this animal model is suitable for investigating the influence of normal luminal bacteria on the cellular immune mechanism in chronic intestinal inflammation.

  2. Ethyl pyruvate ameliorates experimental colitis in mice by inhibiting the HMGB1-Th17 and Th1/Tc1 responses.

    Science.gov (United States)

    Guo, Xianghua; Guo, Runhua; Luo, Xia; Zhou, Lian

    2015-12-01

    Ethyl pyruvate (EP), a simple lipophilic pyruvate ester, has demonstrated protective effects against murine colitis through inhibition the release of inflammatory factor high-mobility group protein box 1 (HMGB1). HMGB1 has been implicated in several autoimmune diseases by inducing Thl and Thl7 cells activation. This study was designed to investigate whether EP amelioration of murine colitis is related to the blocking of the HMGB1-Th17/Thl pathway. We induced murine colitis by intrarectal administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Ethyl pyruvate was injected intraperitoneally once a day for 7days. One week after intrarectal challenge with TNBS, HMGB1, IL-17 and IFN-γ protein levels were remarkably increased following severe colon inflammation. Meanwhile, excessive infiltration of Th17 cells in colonic tissues, and an upregulated proportion of Th17 and Th1/Tc1 cells in the spleen and mesenteric lymph nodes (MLN) were found in the TNBS-treated group compared to the control group. Treatment with the HMGB1 inhibitor EP not only remarkably improved colon pathological damage, but also significantly reduced the number of Th17 cells in the local tissues of the colitis-induced mice. Furthermore, the percentage of Th1/Tc1 and Th17 cells in the spleen and MLN, as well as levels of serum IFN-γ and IL-17A, were all markedly decreased in the EP-treated group. Moreover, in vitro, our results showed that EP in a dose dependent manner inhibited HMGB1 release induced by LPS from CT26 cells (murine colon adenocarcinoma cell line). These results suggest that HMGB1 contributes to the development of murine colitis by promoting the Th17 and Th1/Tc1 responses, and that EP can significantly inhibit HMGB1-Th17 and Thl/Tc1 pathway activation, which may provide better protection to mice with TNBS-induced colitis.

  3. Suppression of NF-κB signaling and NLRP3 inflammasome activation in macrophages is responsible for the amelioration of experimental murine colitis by the natural compound fraxinellone

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xue-Feng; Ouyang, Zi-Jun; Feng, Li-Li; Chen, Gong; Guo, Wen-Jie; Shen, Yan; Wu, Xu-Dong; Sun, Yang, E-mail: yangsun@nju.edu.cn; Xu, Qiang, E-mail: molpharm@163.com

    2014-11-15

    Inflammatory bowel disease (IBD) affects millions of people worldwide. Although the etiology of this disease is uncertain, accumulating evidence indicates a key role for the activated mucosal immune system. In the present study, we examined the effects of the natural compound fraxinellone on dextran sulfate sodium (DSS)-induced colitis in mice, an animal model that mimics IBD. Treatment with fraxinellone significantly reduced weight loss and diarrhea in mice and alleviated the macroscopic and microscopic signs of the disease. In addition, the activities of myeloperoxidase and alkaline phosphatase were markedly suppressed, while the levels of glutathione were increased in colitis tissues following fraxinellone treatment. This compound also decreased the colonic levels of interleukin (IL)-1β, IL-6, IL-18 and tumor necrosis factor (TNF)-α in a concentration-dependent manner. These effects of fraxinellone in mice with experimental colitis were attributed to its inhibition of CD11b{sup +} macrophage infiltration. The mRNA levels of macrophage-related molecules in the colon, including intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), were also markedly inhibited following fraxinellone treatment. The results from in vitro assays showed that fraxinellone significantly reduced lipopolysaccharide (LPS)-induced production of nitric oxide (NO), IL-1β and IL-18 as well as the activity of iNOS in both THP-1 cells and mouse primary peritoneal macrophages. The mechanisms responsible for these effects were attributed to the inhibitory role of fraxinellone in NF-κB signaling and NLRP3 inflammasome activation. Overall, our results support fraxinellone as a novel drug candidate in the treatment of colonic inflammation. - Highlights: • Fraxinellone, a lactone compound, alleviated DSS induced colitis. • The effects of fraxinellone were attributed to its inhibition on

  4. Experimental Study of Relationships between Ultrasonic Attenuation and Dispersion for Ceramic Matrix Composite

    Science.gov (United States)

    Naumenko, A. A.; Shcherbinin, S. A.; Makariev, D. I.; Rybyanets, A. N.

    In this paper an experimental study of different ceramic matrix composites with high elastic losses and dispersion (porous piezoceramics, composites ceramics/crystals) were carried out. Complex sets of elastic, dielectric, and piezoelectric parameters of the porous piezoceramics and ceramic matrix piezocomposites were determined by the impedance spectroscopy method using Piezoelectric Resonance Analysis software. Microstructure of polished and chipped surfaces of composite samples was observed with the optical and scanning electron microcopies. Experimental frequency dependencies of attenuation coefficients and ultrasonic velocities for different ceramic matrix composites were compared with the theoretical results obtained using general Kramers-Kronig relations between the ultrasonic attenuation and dispersion.

  5. Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles.

    Science.gov (United States)

    Naeem, Muhammad; Cao, Jiafu; Choi, Moonjeong; Kim, Woo Seong; Moon, Hyung Ryong; Lee, Bok Luel; Kim, Min-Soo; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy.

  6. TH17 Cell Induction and Effects of IL-17A and IL-17F Blockade in Experimental Colitis

    DEFF Research Database (Denmark)

    Wedebye Schmidt, Esben Gjerløff; Larsen, Hjalte List; Kristensen, Nanna Ny

    2013-01-01

    T helper (TH) 17 cells are believed to play a pivotal role in development of inflammatory bowel disease, and their contribution to intestinal inflammation has been studied in various models of colitis. TH17 cells produce a range of cytokines, some of which are potential targets for immunotherapy...

  7. Fab'-bearing siRNA TNFα-loaded nanoparticles targeted to colonic macrophages offer an effective therapy for experimental colitis.

    Science.gov (United States)

    Laroui, Hamed; Viennois, Emilie; Xiao, Bo; Canup, Brandon S B; Geem, Duke; Denning, Timothy L; Merlin, Didier

    2014-07-28

    Patients suffering from inflammatory bowel disease (IBD) are currently treated by systemic drugs that can have significant side effects. Thus, it would be highly desirable to target TNFα siRNA (a therapeutic molecule) to the inflamed tissue. Here, we demonstrate that TNFα siRNA can be efficiently loaded into nanoparticles (NPs) made of poly (lactic acid) poly (ethylene glycol) block copolymer (PLA-PEG), and that grafting of the Fab' portion of the F4/80 Ab (Fab'-bearing) onto the NP surface via maleimide/thiol group-mediated covalent bonding improves the macrophage (MP)-targeting kinetics of the NPs to RAW264.7 cells in vitro. Direct binding was shown between MPs and the Fab'-bearing NPs. Next, we orally administered hydrogel (chitosan/alginate)-encapsulated Fab'-bearing TNFα-siRNA-loaded NPs to 3% dextran sodium sulfate (DSS)-treated mice and investigated the therapeutic effect on colitis. In vivo, the release of TNFα-siRNA-loaded NPs into the mouse colon attenuated colitis more efficiently when the NPs were covered with Fab'-bearing, compared to uncovered NPs. All DSS-induced parameters of colonic inflammation (e.g., weight loss, myeloperoxidase activity, and Iκbα accumulation) were more attenuated Fab'-bearing NPs loaded with TNFα siRNA than without the Fab'-bearing. Grafting the Fab'-bearing onto the NPs improved the kinetics of endocytosis as well as the MP-targeting ability, as indicated by flow cytometry. Collectively, our results show that Fab'-bearing PLA-PEG NPs are powerful and efficient nanosized tools for delivering siRNAs into colonic macrophages.

  8. Maternal exposure to low levels of corticosterone during lactation protects against experimental inflammatory colitis-induced damage in adult rat offspring.

    Directory of Open Access Journals (Sweden)

    Carla Petrella

    Full Text Available Opposing emotional events (negative/trauma or positive/maternal care during the postnatal period may differentially influence vulnerability to the effects of stress later in life. The development and course of intestinal disorders such as inflammatory bowel disease are negatively affected by persistent stress, but to date the role of positive life events on these pathologies has been entirely unknown. In the present study, the effect of early life beneficial experiences in the development of intestinal dysfunctions, where inflammation and stress stimuli play a primary role, was investigated. As a "positive" experimental model we used adult male rat progeny nursed by mothers whose drinking water was supplemented with moderate doses of corticosterone (CORT (0.2 mg/ml during the lactation period. Such animals have been generally shown to cope better with different environmental situations during life. The susceptibility to inflammatory experimental colitis induced by intracolonic infusion of TNBS (2,4,6-trinitrobenzenesulphonic acid was investigated in CORT-nursed rats in comparison with control rats. This mild increase in maternal corticosterone during lactation induced, in CORT-nursed rats, a long lasting protective effect on TNBS-colitis, characterized by improvements in some indices of the disease (increased colonic myeloperoxidase activity, loss of body weight and food intake and by the involvement of endogenous peripheral pathways known to participate in intestinal disorder development (lower plasma corticosterone levels and colonic mast cell degranulation, alterations in the colonic expression of both corticotrophin releasing factor/CRF and its receptor/CRH-1R. All these findings contribute to suggesting that the reduced vulnerability to TNBS-colitis in CORT-nursed rats is due to recovery from the colonic mucosal barrier dysfunction. Such long lasting changes induced by mild hormonal manipulation during lactation, making the adult also

  9. Colitis ulcerosa

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Jess, Tine; Bjerrum, Jacob Tveiten

    2013-01-01

    Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa affecting approximately 20,000-25,000 Danes. Apart from subgroups with early onset, extensive and long-standing inflammation, or primary sclerosing cholangitis the risk of developing colorectal cancer is of th......Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa affecting approximately 20,000-25,000 Danes. Apart from subgroups with early onset, extensive and long-standing inflammation, or primary sclerosing cholangitis the risk of developing colorectal cancer...

  10. Interleukin-6 induces S100A9 expression in colonic epithelial cells through STAT3 activation in experimental ulcerative colitis.

    Directory of Open Access Journals (Sweden)

    Min Jeoung Lee

    Full Text Available BACKGROUND: Intestinal epithelium is essential for maintaining normal intestinal homeostasis; its breakdown leads to chronic inflammatory pathologies, such as inflammatory bowel diseases (IBDs. Although high concentrations of S100A9 protein and interleukin-6 (IL-6 are found in patients with IBD, the expression mechanism of S100A9 in colonic epithelial cells (CECs remains elusive. We investigated the role of IL-6 in S100A9 expression in CECs using a colitis model. METHODS: IL-6 and S100A9 expression, signal transducer and activator of transcription 3 (STAT3 phosphorylation, and infiltration of immune cells were analyzed in mice with dextran sulfate sodium (DSS-induced colitis. The effects of soluble gp130-Fc protein (sgp130Fc and S100A9 small interfering (si RNA (si-S100A9 on DSS-induced colitis were evaluated. The molecular mechanism of S100A9 expression was investigated in an IL-6-treated Caco-2 cell line using chromatin immunoprecipitation assays. RESULTS: IL-6 concentrations increased significantly in the colon tissues of DSS-treated mice. sgp130Fc or si-S100A9 administration to DSS-treated mice reduced granulocyte infiltration in CECs and induced the down-regulation of S100A9 and colitis disease activity. Treatment with STAT3 inhibitors upon IL-6 stimulation in the Caco-2 cell line demonstrated that IL-6 mediated S100A9 expression through STAT3 activation. Moreover, we found that phospho-STAT3 binds directly to the S100A9 promoter. S100A9 may recruit immune cells into inflamed colon tissues. CONCLUSIONS: Elevated S100A9 expression in CECs mediated by an IL-6/STAT3 signaling cascade may play an important role in the development of colitis.

  11. Berberine is a dopamine D1- and D2-like receptor antagonist and ameliorates experimentally induced colitis by suppressing innate and adaptive immune responses.

    Science.gov (United States)

    Kawano, Masaaki; Takagi, Rie; Kaneko, Atsushi; Matsushita, Sho

    2015-12-15

    Berberine is an herbal alkaloid with various biological activities, including anti-inflammatory and antidepressant effects. Here, we examined the effects of berberine on dopamine receptors and the ensuing anti-inflammatory responses. Berberine was found to be an antagonist at both dopamine D1- and D2-like receptors and ameliorates the development of experimentally induced colitis in mice. In lipopolysaccharide-stimulated immune cells, berberine treatment modified cytokine levels, consistent with the effects of the dopamine receptor specific antagonists SCH23390 and L750667. Our findings indicate that dopamine receptor antagonists suppress innate and adaptive immune responses, providing a foundation for their use in combatting inflammatory diseases.

  12. On Disturbance Attenuation Properties of Control Schemes for Euler-Lagrange Systems : Theoretical and Experimental Results

    NARCIS (Netherlands)

    Scherpen, Jacquelien M.A.; Ortega, Romeo; Escobar, Gerardo

    1997-01-01

    In this paper we analyse and experimentally verify the (local) disturbance attenuation properties of some asymptotically stabilizing nonlinear controllers for Euler-Lagrange systems reported in the literature. Our objective with this study is twofold: first, to compare the performance of these schem

  13. Mangiferin attenuates the symptoms of dextran sulfate sodium-induced colitis in mice via NF-κB and MAPK signaling inactivation.

    Science.gov (United States)

    Dou, Wei; Zhang, Jingjing; Ren, Gaiyan; Ding, Lili; Sun, Aning; Deng, Chao; Wu, Xiaojun; Wei, Xiaohui; Mani, Sridhar; Wang, Zhengtao

    2014-11-01

    Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal (GI) tract, and currently no curative treatment is available. Mangiferin, a natural glucosylxanthone mainly from the fruit, leaves and stem bark of a mango tree, has a strong anti-inflammatory activity. We sought to investigate whether mangiferin attenuates inflammation in a mouse model of chemically induced IBD. Pre-administration of mangiferin significantly attenuated dextran sulfate sodium (DSS)-induced body weight loss, diarrhea, colon shortening and histological injury, which correlated with the decline in the activity of myeloperoxidase (MPO) and the level of tumor necrosis factor-α (TNF-α) in the colon. DSS-induced degradation of inhibitory κBα (IκBα) and the phosphorylation of nuclear factor-kappa B (NF-κB) p65 as well as the mRNA expression of pro-inflammatory mediators (inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), TNF-α, interleukin-1β (IL-1β) and IL-6) in the colon were also downregulated by mangiferin treatment. Additionally, the phosphorylation/activation of DSS-induced mitogen-activated protein kinase (MAPK) proteins was also inhibited by mangiferin treatment. In accordance with the in vivo results, mangiferin exposure blocked TNF-α-stimulated nuclear translocation of NF-κB in RAW264.7 mouse macrophage cells. Transient transfection gene reporter assay performed in TNF-α-stimulated HT-29 human colorectal adenocarcinoma cells indicated that mangiferin inhibits NF-κB transcriptional activity in a dose-dependent manner. The current study clearly demonstrates a protective role for mangiferin in experimental IBD through NF-κB and MAPK signaling inhibition. Since mangiferin is a natural compound with little toxicity, the results may contribute to the effective utilization of mangiferin in the treatment of human IBD.

  14. Intraperitoneal but not intravenous cryopreserved mesenchymal stromal cells home to the inflamed colon and ameliorate experimental colitis.

    Directory of Open Access Journals (Sweden)

    Morgana T L Castelo-Branco

    Full Text Available BACKGROUND AND AIMS: Mesenchymal stromal cells (MSCs were shown to have immunomodulatory activity and have been applied for treating immune-mediated disorders. We compared the homing and therapeutic action of cryopreserved subcutaneous adipose tissue (AT-MSCs and bone marrow-derived mesenchymal stromal cells (BM-MSCs in rats with trinitrobenzene sulfonic acid (TNBS-induced colitis. METHODS: After colonoscopic detection of inflammation AT-MSCs or BM-MSCs were injected intraperitoneally. Colonoscopic and histologic scores were obtained. Density of collagen fibres and apoptotic rates were evaluated. Cytokine levels were measured in supernatants of colon explants. For cell migration studies MSCs and skin fibroblasts were labelled with Tc-99m or CM-DiI and injected intraperitonealy or intravenously. RESULTS: Intraperitoneal injection of AT-MSCs or BM-MSCs reduced the endoscopic and histopathologic severity of colitis, the collagen deposition, and the epithelial apoptosis. Levels of TNF-α and interleukin-1β decreased, while VEGF and TGF-β did not change following cell-therapy. Scintigraphy showed that MSCs migrated towards the inflamed colon and the uptake increased from 0.5 to 24 h. Tc-99m-MSCs injected intravenously distributed into various organs, but not the colon. Cm-DiI-positive MSCs were detected throughout the colon wall 72 h after inoculation, predominantly in the submucosa and muscular layer of inflamed areas. CONCLUSIONS: Intraperitoneally injected cryopreserved MSCs home to and engraft into the inflamed colon and ameliorate TNBS-colitis.

  15. CMV - gastroenteritis/colitis

    Science.gov (United States)

    Colitis - cytomegalovirus; Gastroenteritis - cytomegalovirus; Gastrointestinal CMV disease ... or after bone marrow or organ transplant Ulcerative colitis or Crohn disease Rarely, serious CMV infection involving ...

  16. Anomalous attenuation of extraordinary waves in ionosphere heating experiments experimental results of 2000-2001

    CERN Document Server

    Zabotin, N A; Kovalenko, E S; Frolov, V L; Komrakov, G P; Mityakov, N A; Sergeev, E N

    2001-01-01

    Multiple scattering from artificial random irregularities HF-induced in the ionosphere F region causes significant attenuation of both ordinary and extraordinary radio waves together with the conventional anomalous absorption of ordinary waves due to their conversion into the plasma waves. To study in detail features of this effect, purposeful measurements of the attenuation of weak probing waves of the extraordinary polarization have been performed at the Sura heating facility. Characteristic scale lengths of the involved irregularities are ~0.1-1 km across the geomagnetic field lines. To determine the spectral characteristics of these irregularities from the extraordinary probing wave attenuation measurements, a simple procedure of the inverse problem solving has been implemented and some conclusions about the artificial irregularity features have been drawn. Theory and details of experiments have been stated earlier. This paper reports results of two experimental campaigns carried out in August 2000 and Ju...

  17. MD-1 deficiency attenuates dextran sodium sulfate (DSS)-induced colitis through modulating the function of colonic lamina propria dendritic cells.

    Science.gov (United States)

    Pan, Huaqin; Zhang, Guqin; Zhang, Lin; Wang, Wei; Shang, Jian; Wang, Xiaobing; Zhao, Qiu; Li, Jin

    2016-07-01

    Available evidence suggests that both dysregulated innate and adaptive immune pathways contribute to the aberrant intestinal inflammatory response in patients with inflammatory bowel disease (IBD). Myeloid Differentiation 1 (MD-1), also known as Lymphocyte Antigen 86 (Ly86), a secreted protein interacting with radioprotective 105 (RP105), plays an important role in Toll-like receptor 4 (TLR4) signaling pathway. Previous studies showed that MD-1 may be involved in the (patho) physiological regulation of the innate immune system and inflammation. In this study, we reported for the first time that MD-1 mRNA expression was up-regulated in both human IBD patients and DSS-treated WT mice. We showed that MD-1(-/-) mice were less susceptible to the development of colitis than WT controls as demonstrated by significantly reduced weight loss, disease activity index, colon histological scores, cellular infiltration and expression of inflammatory mediators. In addition, mucosal barrier function seemed to be intact in response to the loss of MD-1. Finally, lamina propria dendritic cells (LPDCs) from the colon of MD-1(-/-) mice after DSS exposure not only decreased in number but also significantly down-regulated the expression of surface maturation co-stimulatory molecules MHC-II, CD40 and CD86 compared with those from WT mice. Taken together, our results reveal that MD-1 deficiency is of critical importance in down-regulating induction and progression of DSS colitis, thereby suggesting that MD-1 might be a target for future interventional therapies of IBD.

  18. Hydroalcoholic Extract from Inflorescences of Achyrocline satureioides (Compositae) Ameliorates Dextran Sulphate Sodium-Induced Colitis in Mice by Attenuation in the Production of Inflammatory Cytokines and Oxidative Mediators

    Science.gov (United States)

    da Silva, Luisa Mota; Farias, Jaime Antonio Machado; Boeing, Thaise; Somensi, Lincon Bordignon; Beber, Ana Paula; Cury, Benhur Judah

    2016-01-01

    Achyrocline satureioides is a South American herb used to treat inflammatory and gastrointestinal diseases. This study evaluated intestinal anti-inflammatory effects of the hydroalcoholic extract of inflorescences of satureioides (HEAS) in dextran sulfate sodium (DSS) induced colitis in mice. Mice were orally treated with vehicle, 5-aminosalicylic acid (100 mg/kg), or HEAS (1–100 mg/kg). Clinical signs of colitis and colonic histopathological parameters were evaluated, along with the determination of levels of reduced glutathione and lipid hydroperoxide (LOOH), the superoxide dismutase (SOD), and myeloperoxidase (MPO) activity in colon. The colonic content of cytokines (TNF, IL-4, IL-6, and IL-10) was measured. Additionally, the effects of the extract on nitric oxide (NO) release by lipopolysaccharide (LPS) stimulated macrophages and diphenylpicrylhydrazyl levels were determined. Mucin levels and SOD activity, as well as the LOOH, MPO, TNF, and IL-6 accumulation in colon tissues, were normalized by the HEAS administration. In addition, the extract elicited an increase in IL-4 and IL-10 levels in colon. NO release by macrophages was inhibited by HEAS and its scavenger activity was confirmed. Together these results suggest that preparations obtained from inflorescences from A. satureioides could be used in treatment for IBD. Besides, this work corroborates the popular use of A. satureioides in inflammatory disorders. PMID:27847525

  19. Hydroalcoholic Extract from Inflorescences of Achyrocline satureioides (Compositae Ameliorates Dextran Sulphate Sodium-Induced Colitis in Mice by Attenuation in the Production of Inflammatory Cytokines and Oxidative Mediators

    Directory of Open Access Journals (Sweden)

    Luisa Mota da Silva

    2016-01-01

    Full Text Available Achyrocline satureioides is a South American herb used to treat inflammatory and gastrointestinal diseases. This study evaluated intestinal anti-inflammatory effects of the hydroalcoholic extract of inflorescences of satureioides (HEAS in dextran sulfate sodium (DSS induced colitis in mice. Mice were orally treated with vehicle, 5-aminosalicylic acid (100 mg/kg, or HEAS (1–100 mg/kg. Clinical signs of colitis and colonic histopathological parameters were evaluated, along with the determination of levels of reduced glutathione and lipid hydroperoxide (LOOH, the superoxide dismutase (SOD, and myeloperoxidase (MPO activity in colon. The colonic content of cytokines (TNF, IL-4, IL-6, and IL-10 was measured. Additionally, the effects of the extract on nitric oxide (NO release by lipopolysaccharide (LPS stimulated macrophages and diphenylpicrylhydrazyl levels were determined. Mucin levels and SOD activity, as well as the LOOH, MPO, TNF, and IL-6 accumulation in colon tissues, were normalized by the HEAS administration. In addition, the extract elicited an increase in IL-4 and IL-10 levels in colon. NO release by macrophages was inhibited by HEAS and its scavenger activity was confirmed. Together these results suggest that preparations obtained from inflorescences from A. satureioides could be used in treatment for IBD. Besides, this work corroborates the popular use of A. satureioides in inflammatory disorders.

  20. Jumihaidokuto effectively inhibits colon inflammation and apoptosis in mice with acute colitis.

    Science.gov (United States)

    Sreedhar, Remya; Arumugam, Somasundaram; Karuppagounder, Vengadeshprabhu; Thandavarayan, Rajarajan A; Giridharan, Vijayasree V; Pitchaimani, Vigneshwaran; Afrin, Mst Rejina; Harima, Meilei; Nakamura, Takashi; Nakamura, Masahiko; Suzuki, Kenji; Watanabe, Kenichi

    2015-12-01

    Jumihaidokuto, a Japanese kampo medicine, is prescribed in Japan for its anti-inflammatory activity. Here we have examined its beneficial effects against acute colitis induced by dextran sulfate sodium (DSS) in mice. We have used C57BL/6 female mice, divided into two groups and received 3% DSS in drinking water during the experimental period (8days). Treatment group mice received 1g/kg/day dose of Jumihaidokuto orally whereas DSS control group received equal volume of distilled water. Normal control group mice received plain drinking water. Jumihaidokuto treatment attenuated the colitis symptoms along with suppression of various inflammatory marker proteins such as IL-1β, IL-2Rα, IL-4, CTGF and RAGE. It has also down-regulated the oxidative stress and apoptotic signaling in the colons of mice with colitis. The present study has confirmed the beneficial effects of Jumihaidokuto on DSS induced acute colitis in mice and suggests that it can be a potential agent for the treatment of colitis.

  1. Pseudomembranous colitis complicating ulcerative colitis.

    Science.gov (United States)

    Kawaratani, Hideto; Tsujimoto, Tatsuhiro; Toyohara, Masahisa; Kin, Kenichi; Taniguchi, Tomoyasu; Shirai, Yasuyo; Ikenaka, Yasuhide; Nakayama, Masaki; Fujii, Hisao; Fukui, Hiroshi

    2010-10-01

    Clostridium difficile toxin (CD toxin) causes antibiotic-associated colitis, or pseudomembranous colitis (PMC). Although CD toxin is sometimes found in the stools of patients with ulcerative colitis (UC), UC is rarely complicated by PMC. We report herein a case of PMC complicating UC, and present a review of the literature. A 71-year-old woman was diagnosed as having UC of the left colon, and treated with prednisolone and mesalazine. Later, however, lumbar spinal stenosis was also detected. After surgery for lumbar spinal stenosis, she suffered postoperative infection of the lumbar region. After 3-week treatment with antibiotics, she developed diarrhea, bloody stools, and abdominal pain. Colonoscopy revealed PMC of the cecum, ascending colon, sigmoid colon, and rectum. Stools were positive for CD toxin. As cefotiam hydrochloride, levofloxacin hydrate (LVFX), and prednisolone were suspected as the causative agents, she was treated with 1.5 g vancomycin (VCM) daily for 2 weeks without ceasing LVFX. Her symptoms improved, and colonoscopy confirmed resolution of PMC. The possibility of PMC should be considered in UC patients treated with antibiotics, immunosuppressive agents or corticosteroids who complain of gastrointestinal symptoms. These patients should be thoroughly investigated by several modalities, including colonoscopy and CD toxin testing.

  2. Dietary olive oil supplemented with fish oil, rich in EPA and DHA (n-3) polyunsaturated fatty acids, attenuates colonic inflammation in rats with DSS-induced colitis.

    Science.gov (United States)

    Camuesco, Desirée; Gálvez, Julio; Nieto, Ana; Comalada, Mònica; Rodríguez-Cabezas, M Elena; Concha, Angel; Xaus, Jordi; Zarzuelo, Antonio

    2005-04-01

    Previous studies proposed a protective role of the dietary intake of (n-3) PUFA in human inflammatory bowel disease (IBD), but almost no studies have been performed using olive oil. The aims of the present study were to test the beneficial effects of an olive oil-based diet with or without fish oil, rich in (n-3) PUFA, in the dextran sodium sulfate (DSS) model of rat colitis and to elucidate the mechanisms involved in their potential beneficial effects, with special attention to the production of some of the mediators involved in the intestinal inflammatory response, such as leukotriene B(4) (LTB(4)), tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO). Rats were fed the different diets for 2 wk before colitis induction and thereafter until colonic evaluation 15 d later. Colitic rats fed the olive oil-based diet had a lower colonic inflammatory response than those fed the soybean oil diet, and this beneficial effect was increased by the dietary incorporation of (n-3) PUFA. A restoration of colonic glutathione levels and lower colonic NO synthase expression occurred in all colitic rats fed an olive oil diet compared with the control colitic group that consumed the soybean oil diet. However, (n-3) PUFA incorporation into an olive oil diet significantly decreased colonic TNFalpha and LTB(4) levels compared with colitic rats that were not supplemented with fish oil. These results affirm the benefits of an olive oil diet in the management of IBD, which are further enhanced by the addition of (n-3) PUFA.

  3. Colitis ulcerosa

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Jess, Tine; Bjerrum, Jacob Tveiten;

    2013-01-01

    Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa affecting approximately 20,000-25,000 Danes. Apart from subgroups with early onset, extensive and long-standing inflammation, or primary sclerosing cholangitis the risk of developing colorectal cancer...... is of the same magnitude as in the background population. The symptoms are usually diarrhoea including bloody stools, rectal tenesmi, anaemia, and fatigue. This review is an update on diagnostics and treatment strategies of relevance for clinicians, and as UC often affects patients during their peak reproductive...

  4. Experimental measurements of ultrasonic propagation velocity and attenuation in a magnetic fluid.

    Science.gov (United States)

    Motozawa, M; Iizuka, Y; Sawada, T

    2008-05-21

    The ultrasonic propagation velocity and attenuation in a magnetic fluid subjected to magnetic field are measured precisely. Various characteristic properties of ultrasonic propagation in magnetic fluid such as hysteresis and anisotropy are observed. These results show that the ultrasonic propagation velocity and attenuation are dependent upon the intensity and the length of time for which the magnetic field is applied. When the magnetic field is applied, some of the magnetic particles in the magnetic fluid form clustering structures that influence ultrasonic propagation in a magnetic fluid. Our results indicate that the inner structure of a magnetic fluid can be analysed experimentally and we discuss the application of this non-contact inspection of the clustering structures in a magnetic fluid by ultrasonic techniques.

  5. Telmisartan attenuates colon inflammation, oxidative perturbations and apoptosis in a rat model of experimental inflammatory bowel disease.

    Directory of Open Access Journals (Sweden)

    Hany H Arab

    Full Text Available Accumulating evidence has indicated the implication of angiotensin II in the pathogenesis of inflammatory bowel diseases (IBD via its proinflammatory features. Telmisartan (TLM is an angiotensin II receptor antagonist with marked anti-inflammatory and antioxidant actions that mediated its cardio-, reno- and hepatoprotective actions. However, its impact on IBD has not been previously explored. Thus, we aimed to investigate the potential alleviating effects of TLM in tri-nitrobenezene sulphonic acid (TNBS-induced colitis in rats. Pretreatment with TLM (10 mg/kg p.o. attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI, colon weight/length ratio, macroscopic damage, histopathological findings and leukocyte migration. TLM suppressed the inflammatory response via attenuation of tumor necrosis factor-α (TNF-α, prostaglandin E2 (PGE2 and myeloperoxidase (MPO activity as a marker of neutrophil infiltration besides restoration of interleukin-10 (IL-10. TLM also suppressed mRNA and protein expression of nuclear factor kappa B (NF-κB p65 and mRNA of cyclo-oxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS proinflammatory genes with concomitant upregulation of PPAR-γ. The alleviation of TLM to colon injury was also associated with inhibition of oxidative stress as evidenced by suppression of lipid peroxides and nitric oxide (NO besides boosting glutathione (GSH, total anti-oxidant capacity (TAC and the activities of superoxide dismutase (SOD and glutathione peroxidase (GPx. With respect to apoptosis, TLM downregulated the increased mRNA, protein expression and activity of caspase-3. It also suppressed the elevation of cytochrome c and Bax mRNA besides the upregulation of Bcl-2. Together, these findings highlight evidences for the beneficial effects of TLM in IBD which are mediated through modulation of colonic inflammation, oxidative stress and apoptosis.

  6. Omega 3 fatty acids supplementation has an ameliorative effect in experimental ulcerative colitis despite increased colonic neutrophil infiltration Los suplementos de ácidos grasos omega 3 tienen efectos beneficiosos en colitis ulcerosa a pesar del aumento de la infiltracción por neutrófilos del colon

    Directory of Open Access Journals (Sweden)

    Ioannis Varnalidis

    2011-10-01

    Full Text Available Purpose: omega 3 polyunsaturated fatty acids have anti-inflammatory properties and can be beneficial in the treatment of inflammatory diseases, such as ulcerative colitis. Dextran sodium sulphate (DSS colitis in rats appears to mimic nearly all of the morphological characteristics and lesion distributions of ulcerative colitis. The purpose of the current study was to investigate the efficacy of omega 3 fatty acids in the treatment of experimental ulcerative colitis. Methods: thirty-six Wistar rats were randomly assigned to group A or group B receiving 5% dextran sulfate sodium (DSS in their drinking water for eight days. For the next eight days post-DSS, group A animals received tap-water, and group B animals were fed a nutritional solution containing high levels of omega 3 polyunsaturated fatty acids (ProSure®, Abbott Laboratories, Zwolle, Netherlands once per day, administrated with a orogastric feeding tube. Results: animals fed an omega 3 rich diet exhibited a statistically significant increase in hematocrit and hemoglobin levels, compared to animals drinking tap water, and a trend towards histopathological and clinical improvement, with the administration of omega 3 fatty acids ameliorating epithelial erosion by day 8 post-DSS, but no statistically significant difference was observed between group A and group B animals at 4 or 8 days post-DSS. Also, a statistically significant increase in neutrophil infiltration was observed, as depicted by myelohyperoxidase activity. Conclusion: our findings support a positive role of omega 3 polyunsaturated fatty acids supplementation in an experimental model of ulcerative colitis despite the increased colonic neutrophil infiltration. Further studies are needed in order to investigate the role of increased neutrophils in colonic mucosa.

  7. Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue.

    Science.gov (United States)

    Cotton, James A; Motta, Jean-Paul; Schenck, L Patrick; Hirota, Simon A; Beck, Paul L; Buret, Andre G

    2014-01-01

    Giardia duodenalis (syn. G. intestinalis, G. lamblia) is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs) are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time that certain

  8. Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue.

    Directory of Open Access Journals (Sweden)

    James A Cotton

    Full Text Available Giardia duodenalis (syn. G. intestinalis, G. lamblia is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time

  9. Brachyspira murdochii colitis in pigs

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre; Christensen, A. S.; Boye, Mette

    2010-01-01

    The weakly beta-hemolytic porcine spirochete Brachyspira murdochii is considered a normal intestinal commensal. In the present study, however, a field case of B murdochii–associated catarrhal colitis was identified in a pig, as characterized by extensive spirochetal colonization of the surface...... epithelium. Experimentally, 8 weaned pigs were challenged with the B murdochii isolate, reproducing catarrhal colitis in 2 animals. By applying fluorescent in situ hybridization using a species-specific oligonucleotide probe targeting 23S rRNA, B murdochii organisms were found in high numbers and were...... closely associated with the surface epithelium in the pigs with catarrhal colitis. The results indicate that, when present in high numbers, B murdochii is low pathogenic for pigs....

  10. Eosinophilic colitis

    Institute of Scientific and Technical Information of China (English)

    Nnenna Okpara; Bassam Aswad; Gyorgy Baffy

    2009-01-01

    Eosinophilic colitis (EC) is a rare form of primary eosinophilic gastrointestinal disease with a bimodal peak of prevalence in neonates and young adults. EC remains a little understood condition in contrast to the increasingly recognized eosinophilic esophagitis. Clinical presentation of EC is highly variable according to mucosal, transmural, or serosal predominance of inflammation. EC has a broad differential diagnosis because colon tissue eosinophilia often occurs in parasitic infection, drug-induced allergic reactions,inflammatory bowel disease, and various connective tissue disorders, which require thorough searching for secondary causes that may be specifically treated with antibiotics or dietary and drug elimination.Like eosinophilic gastrointestinal disease involving other segments of the gastrointestinal tract, EC responds very well to steroids that may be spared by using antihistamines, leukotriene inhibitors and biologics.

  11. Nitric oxide and chronic colitis

    Directory of Open Access Journals (Sweden)

    Matthew B Grisham

    1996-01-01

    Full Text Available Nitric oxide (NO is thought to play an important role in modulating the inflammatory response by virtue of its ability to affect bloodflow, leukocyte function and cell viability. The objective of this study was to assess the role that NO may play in mediating the mucosal injury and inflammation in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS. Chronic granulomatous colitis with liver and spleen inflammation was induced in female Lewis rats via the subserosal (intramural injection of peptidoglycan/polysaccharide (PG/PS derived from group A streptococci. Chronic NOS inhibition by oral administration of NG-nitro-L-arginine methyl ester (L-NAME (15 µmol/kg/day or amino-guanidine (AG (15 µmol/ kg/day was found to attenuate the PG/PS-induced increases in macroscopic colonic inflammation scores and colonic myeloperoxidase activity. Only AG -- not L-NAME – attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen weight whereas neither was effective at significantly attenuating the PG/PS-induced increases in liver weight. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG produced significantly lower values (38±3 versus 83±8 µM, respectively, P<0.05. Finally, L-NAME, but not AG, administration significantly increased mean arterial pressure from 83 mmHg in colitic animals to 105 mmHg in the PG/PS+ L-NAME-treated animals (P<0.05. It is concluded that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

  12. Pseudomembranous collagenous colitis.

    Science.gov (United States)

    Yuan, Shan; Reyes, Victoria; Bronner, Mary P

    2003-10-01

    The classic clinical and histologic features of collagenous colitis are well characterized; however, the acute or neutrophilic inflammatory changes that may accompany this entity are less well established. In this report of 10 patients, we describe the first series of pseudomembranous collagenous colitis. Because superimposed Clostridium difficile infection was only demonstrated in one patient and no other causes of pseudomembranous colitis were evident in the remaining nine patients, we conclude that pseudomembranes are part of the spectrum of collagenous colitis itself. This case series illustrates the importance of searching for collagenous colitis in the evaluation of pseudomembranous colitis. At the same time, superimposed infectious or ischemic etiologies need to be excluded clinically in any patient with superimposed pseudomembranes. The existence of pseudomembranes in collagenous colitis also lends support to the hypothesis that toxin- and/or ischemia-mediated injury may be involved in the pathogenesis of collagenous colitis.

  13. Effect of Changxieting Capsules on Experimental Colitis in Rats%肠泻停胶囊对实验性结肠炎大鼠的影响

    Institute of Scientific and Technical Information of China (English)

    陈晓莉; 彭洁; 乔逸

    2012-01-01

    目的:探讨肠泻停胶囊对三硝基苯磺酸(TNBS)诱导大鼠实验性结肠炎的影响.方法:120只SD大鼠随机分为6组,每组20只:正常组、模型组、阳性对照组、肠泻停胶囊高、中、低组.除正常对照组未行造模外,其余五组大鼠均采用TNBS造模.肠泻停胶囊高、中、低组分别灌胃给药(1.80,0.90,0.45 g /kg体质量)、阳性对照组灌胃给予地塞米松剂量(0.2 mg/kg体质量)、其余组灌胃给予0.5%羧甲基纤维素钠溶液连续3 周、4周;观察肠泻停胶囊对大鼠腹泻率、死亡率、血白细胞计数、淋巴细胞百分率、脾脏及胸腺重量、组织形态学评分、组织MPO活性的影响.结果:经肠泻停胶囊干预后各剂量组动物腹泻明显缓解,腹泻率降低,动物死亡率降低,外周血WBC、LYM值及组织MPO值降低,剖检可见结肠组织溃疡面积明显缩小,水肿缓解,坏死减轻,未见肠壁增厚.结论:肠泻停胶囊连续给药,对实验性结肠炎治疗作用显著.%Objective: To explore the effect of Changxieting capsules ( CXT ) on trinitrobenzene sulfonic acid ( TNBS )-induced ex-perimental colitis in rats. Method: 120 rats were randomly divided into the following six groups( 20 in each group ), the normal group, model group,control group,CXT capsule group with high, medium and low dose, respectively. The experimental colitis in rats were induced by TNBS in the groups except those in the normal group. The rats in the CXT capsule group with high, medium and low dose were given CXT capsules ( 1. 80, 0. 90 and 0. 45 g/kg body weight ), those in the control group were given dexamethasone ( 0. 2 mg / kg body weight ) and those in the normal group and model group were given 0. 5% sodium carboxymethyl cellulose through intragastric administration for 3w and 4w. The effects of CXT capsules on diarrhea percent, mortality, white cell count, lymphocyte percent, spleen and thymus weight, histomorphology score and tissue MPO activity were

  14. Escherichia coli strain Nissle 1917 ameliorates experimental colitis by modulating intestinal permeability, the inflammatory response and clinical signs in a faecal transplantation model.

    Science.gov (United States)

    Souza, Éricka L; Elian, Samir D; Paula, Laís M; Garcia, Cristiana C; Vieira, Angélica T; Teixeira, Mauro M; Arantes, Rosa M; Nicoli, Jacques R; Martins, Flaviano S

    2016-03-01

    Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions of the gut that include ulcerative colitis and Crohn's disease. Probiotics are live micro-organisms that may be used as adjuvant therapy for patients with IBD. The aim of this study was to evaluate the effect of prophylactic ingestion of Escherichia coli strain Nissle 1917 (EcN) in a murine model of colitis. For induction of colitis, mice were given a 3.5% dextran sodium sulfate (DSS) solution for 7 days in drinking water. EcN administration to mice subjected to DSS-induced colitis resulted in significant reduction in clinical and histopathological signs of disease and preservation of intestinal permeability. We observed reduced inflammation, as assessed by reduced levels of neutrophils, eosinophils, chemokines and cytokines. We observed an increase in the number of regulatory T-cells in Peyer's patches. Germ-free mice received faecal content from control or EcN-treated mice and were then subjected to DSS-induced colitis. We observed protection from colitis in animals that were colonized with faecal content from EcN-treated mice. These results suggest that preventative oral administration of EcN or faecal microbiota transplantation with EcN-containing microbiota ameliorates DSS-induced colitis by modifying inflammatory responsiveness to DSS.

  15. Catechin-7-O-β-D-glucopyranoside isolated from the seed of Phaseolus calcaratus Roxburgh ameliorates experimental colitis in rats.

    Science.gov (United States)

    Kook, Sung-Ho; Choi, Ki Choon; Cho, Seong-Wan; Cho, Hyoung-Kwon; Lee, Kyung Dong; Lee, Jeong-Chae

    2015-12-01

    The seeds of Phaseolus calcaratus Roxburgh (PHCR) are common legumes that comprise part of the daily diet in Chinese and Korean culture. Recent findings highlight anti-inflammatory and anti-septic potentials of catechin-7-O-β-D-glucopyranoside (CGP) isolated from PHCR seeds. We investigated the intestinal anti-inflammatory activity and associated mechanisms of CGP using a rat model of trinitrobenzenesulfonic acid (TNBS)-induced colitis. Oral treatment with CGP (10mg/kg body weight) suppressed body weight loss and intestinal inflammatory damages in TNBS-induced colitic rats. This treatment reduced myeloperoxidase activity and malondialdehyde level, but increased glutathione level in the TNBS colitic rats. CGP treatment also inhibited the TNBS-mediated increases in nitric oxide synthase, cyclooxygenase-2, interleukin-1β, tumor necrosis factor-α, intercellular adhesion molecule-1, and monocyte chemotactic protein-1 proteins or mRNA levels. This inhibition was accompanied by the increased mRNA levels of mucins MUC2 and MUC3. The CGP treatment prevented phosphorylation of p38 mitogen-activated protein kinase, IκB-α, and DNA-nuclear factor-κB binding, all of which were increased in the inflamed colons of TNBS-treated rats. Furthermore, oral administration with a crude PHCR butanol extract (100mg/kg body weight) which contains 1.5% of CGP showed intestinal anti-inflammatory potentials similar to that of CGP. Collectively, our current findings suggest that CGP or CGP-containing PHCR seeds may have favorable effects on intestinal inflammatory diseases.

  16. Colon-targeted cell-permeable NFκB inhibitory peptide is orally active against experimental colitis.

    Science.gov (United States)

    Hong, Sungchae; Yum, Soohwan; Yoo, Hyun-Jung; Kang, Sookjin; Yoon, Jeong-Hyun; Min, Dosik; Kim, Young Mi; Jung, Yunjin

    2012-05-07

    For the purpose of development of orally active peptide therapeutics targeting NFκB for treatment of inflammatory bowel disease (IBD), two major barriers in oral delivery of therapeutic peptides, metabolic lability and tissue impermeability, were circumvented by introduction of a colon-targeted delivery system and cell permeable peptides (CPP) to NFκB inhibitory peptides (NIP). Suppression of NFκB activation was compared following treatment with various CPP conjugated NIPs (CPP-NIP). The most potent CPP-NIP was loaded in a capsule coated with a colon specific polymer, which was administered orally to colitic rats. The anti-inflammatory activity of the colon-targeted CPP-NIP was evaluated by measuring inflammatory indices in the inflamed colonic tissue. For confirmation of the local action of the CPP-NIP, the same experiment was done after rectal administration. Tissue permeability of the CPP-NIP was examined microscopically and spectrophotometrically using FITC-labeled CPP-NIP (CPP-NIP-FITC). NEMO binding domain peptide (NBD, TALDWSWLQTE) fused with a cell permeable peptide CTP (YGRRARRRARR), CTP-NBD, was most potent in inhibiting NFκB activity in cells. Colon-targeted CTP-NBD, but not colon-targeted NBD and CTP-NBD in an enteric capsule, ameliorated the colonic injury, which was in parallel with decrease in MPO activity and the levels of inflammatory mediators. Intracolonic treatment with CTP-NBD alleviated rat colitis and improved all the inflammatory indicators. CTP-NBD-FITC was detected at much greater level in the inflamed tissue than was NBD-FITC. Taken together, introduction of cell permeability and colon targetability to NIP may be a feasible strategy for an orally active peptide therapy for treatment of IBD.

  17. Pleurotus tuber-regium Polysaccharides Attenuate Hyperglycemia and Oxidative Stress in Experimental Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Hui-Yu Huang

    2012-01-01

    Full Text Available Pleurotus tuber-regium contains polysaccharides that are responsible for pharmacological actions, and medicinal effects of these polysaccharides have not yet been studied in diabetic rats. We examined the antidiabetic, antihyperlipidemic, and antioxidant properties of P. tuber-regium polysaccharides in experimental diabetic rats. Forty rats were equally assigned as diabetic high-fat (DHF diet and polysaccharides treated DHF groups (DHF+1P, DHF+2P, and DHF+3P, 20 mg/kg bodyweight/8-week. Diabetes was induced by chronic low-dose streptozotocin injections and a high-fat diet to mimic type 2 diabetes. Polysaccharides (1P, 2P, and 3P were extracted from three different strains of P. tuber-regium. Fasting blood glucose and glycosylated hemoglobin (HbA1c levels substantially decreased, while serum insulin levels were restored by polysaccharides treatment compared to DHF. Furthermore, plasma total cholesterol, triglycerides, and low-density lipoprotein levels were significantly (P<0.01 lower in polysaccharide groups. High-density lipoprotein levels were attenuated with polysaccharides against diabetes condition. Polysaccharides inhibited (P<0.01 the lipid peroxidation index (malondialdehyde, and restored superoxide dismutase and glutathione peroxidase activities in the liver of diabetic rats. The antihyperglycemic property of polysaccharides perhaps boosts the antioxidant system that attenuates oxidative stress. We emphasize that P. tuber-regium polysaccharides can be considered as an alternative medicine to treat hyperglycemia and oxidative stress in diabetic rats.

  18. Experimental Investigation on Electromagnetic Attenuation by Low Pressure Radio-Frequency Plasma for Cavity Structure

    Science.gov (United States)

    He, Xiang; Zhang, Yachun; Chen, Jianping; Chen, Yudong; Zeng, Xiaojun; Yao, Hong; Tang, Chunmei

    2016-01-01

    This paper reports on an experiment designed to test electromagnetic (EM) attenuation by radio-frequency (RF) plasma for cavity structures. A plasma reactor, in the shape of a hollow cylinder, filled with argon gas at low pressure, driven by a RF power source, was produced by wave-transmitting material. The detailed attenuations of EM waves were investigated under different conditions: the incident frequency is 1-4 GHz, the RF power supply is 13.56 MHz and 1.6-3 kW, and the argon pressure is 75-200 Pa. The experimental results indicate that 5-15 dB return loss can be obtained. From a first estimation, the electron density in the experiment is approximately (1.5-2.2) × 1016 m-3 and the collision frequency is about 11-30 GHz. The return loss of EM waves was calculated using a finite-difference time-domain (FDTD) method and it was found that it has a similar development with measurement. It can be confirmed that RF plasma is useful in the stealth of cavity structures such as jet-engine inlet. supported by National Natural Science Foundation of China (No. 51107033) and the Fundamental Research Funds for the Central Universities of China (No. 2013B33614)

  19. Attenuation properties of cement composites: Experimental measurements and Monte Carlo calculations

    Science.gov (United States)

    Florez Meza, Raul Fernando

    Developing new cement based materials with excellent mechanical and attenuation properties is critically important for both medical and nuclear power industries. Concrete continues to be the primary choice material for the shielding of gamma and neutron radiation in facilities such as nuclear reactors, nuclear waste repositories, spent nuclear fuel pools, heavy particle radiotherapy rooms, particles accelerators, among others. The purpose of this research was to manufacture cement pastes modified with magnetite and samarium oxide and evaluate the feasibility of utilizing them for shielding of gamma and neutron radiation. Two different experiments were conducted to accomplish these goals. In the first one, Portland cement pastes modified with different loading of fine magnetite were fabricated and investigated for application in gamma radiation shielding. The experimental results were verified theoretically through XCOM and the Monte Carlo N-Particle (MCNP) transport code. Scanning electron microscopy and x-ray diffraction tests were used to investigate the microstructure of the samples. Mechanical characterization was also perfornmed by compression testing. The results suggest that fine magnetite is a suitable aggregate for increasing the compressive and flexural strength of white Portland cement pastes; however, there is no improvement of the attenuation at intermediate energy (662 keV). For the second experiment, cement pastes with different concentrations of samarium oxide were fabricated and tested for shielding against thermal neutrons. MCNP simulations were used to validate the experimental work. The result shows that samarium oxide increases the effective thermal cross section of Portland cement and has the potential to replace boron bearing compounds currently used in neutron shielding.

  20. The effect of progesterone in the prevention of the chemically induced experimental colitis in rats Efeito da progesterona na prevenção de colite experimental induzida quimicamente em ratos

    Directory of Open Access Journals (Sweden)

    Oguzhan Karatepe

    2012-01-01

    Full Text Available PURPOSE: To study the effects of progesterone on an experimental colitis model. METHODS: Wistar albino rats were treated subcutaneously with 2mg/kg once a day during seven days Colitis was induced by intrarectal administration of 5mg trinitrobenzene sulfonic acid (TNBS. Disease activities, macroscopic and microscopic scores were evaluated. To determine the response provoked by progesterone we measured Colonic malondialdehyde (MDA, TNF alfa, IL-6 and Nitric oxide (NO levels in addition to the MPO (Myeloperoxidase and caspase-3 activities. RESULTS: Progesterone ameliorated significantly the macroscopic and microscopic scores. TNBS-induced colitis significantly increased the colonic MDA levels and caspase-3 activities in group 2 in comparison to the control group. The results of the study revealed a decline in MDA, NO, IL6 and TNF-α levels in the colon tissue and in blood due to progesterone therapy in group 3 when compared to the group 2, a significant improvement. Progesterone treatment was associated with decreased MDA, MPO, TNF alfa and caspase-3 activity. CONCLUSION: Progesterone therapy decreased oxidative damage in the colonic mucosa.OBJETIVO: Investigar os efeitos da progesterona em um modelo de colite experimental. MÉTODOS: Ratos albinos Wistar foram tratados subcutaneamente com 2mg/kg por dia durante sete dias. A colite foi induzida por administração intrarretal de 5mg ácido sulfônico trinitrobenzeno (TNBS. Foram avaliadas as atividades da doença, escores macroscópicos e microscópicos Para determinar a resposta provocada pela progesterona foi medida no cólon os níveis de malondialdeído (MDA, TNF alfa, IL-6 e óxido nítrico (NO, além da atividade da MPO (Myeloperoxidase e caspase-3. RESULTADOS: A progesterone melhorou significantemente os escores macroscópicos e microscópicos. A colite induzida pelo TNBS significantemente aumentou os níveis colônicos de MDA e a atividade da caspase-3 no grupo 2 em comparação com o grupo

  1. Doenjang prepared with mixed starter cultures attenuates azoxymethane and dextran sulfate sodium-induced colitis-associated colon carcinogenesis in mice

    Directory of Open Access Journals (Sweden)

    Ji-Kang Jeong

    2014-01-01

    Full Text Available Backgrounds: Doenjang is traditional Korean fermented soybean paste and widely known for its various health benefits including anticancer effect. In this study, we manufactured doenjang with the grain-type meju using probiotic mixed starter cultures of Aspegillus oryzae, Bacillus subtilis-SKm, and Lactococcus lactis-GAm to improve the qualities and beneficial properties of doenjang. Materials and Methods: The inhibitory effects of the doenjang prepared with the grain-type meju using mixed starter cultures were investigated in azoxymethane (AOM and dextran sulfate sodium (DSS-induced colon carcinogenesis mice model. AOM and DSS colon carcinogenesis was induced in female C57BL/6 mice, and doenjang was orally administered for 4 weeks. Body weight, colon length, and colon weight of mice were determined, and colonic tissues were histologically evaluated. The serum levels of proinflammatory cytokines as well as the expression of inflammation- and apoptosis-related genes in colonic tissue were also analyzed. Results: Administration of the doenjang using probiotic mixed starter cultures ameliorated the symptoms of colon cancer, and reduced the incidence of neoplasia, and reduced the levels of serum proinflammatory cytokines such as interleukin-6, and tumor necrosis factor-α and inducible nitric oxide synthase and cycloooxygenase-2 expression levels in colonic tissue. In addition, it increased Bax and reduced Bcl-2 expression levels and increased p21 and p53 expression in the colonic tissues. Conclusion: These findings indicate that the doenjang attenuated colon carcinogenesis induced by AOM and DSS by ameliorating the symptoms of colon cancer, reducing the occurrence of neoplasia, regulating proinflammatory cytokine levels, and controlling the expressions of inflammation- and apoptosis-related genes in the colonic tissue.

  2. Crohn's & Colitis Foundation of America

    Science.gov (United States)

    ... enabled to enjoy the full interactive experience. Crohn's & Colitis Foundation of America Find a Doctor Find a ... Local Chapters News Events Search: What are Crohn's & Colitis? What is Crohn's Disease What is Ulcerative Colitis ...

  3. Genetics Home Reference: ulcerative colitis

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions ulcerative colitis ulcerative colitis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Ulcerative colitis is a chronic disorder that affects the digestive ...

  4. Effect of COX-2 inhibitor lumiracoxib and the TNF-α antagonist etanercept on TNBS-induced colitis in Wistar rats.

    Science.gov (United States)

    Paiotti, Ana Paula Ribeiro; Ribeiro, Daniel Araki; Silva, Roseane Mendes; Marchi, Patrícia; Oshima, Celina Tizuko Fujiyama; Neto, Ricardo Artigiani; Miszputen, Sender Jankiel; Franco, Marcello

    2012-06-01

    Crohn's disease (CD) is associated with gut barrier dysfunction. Besides the baseline barrier defect, a subgroup of patients also expresses an intestinal barrier hyperresponsiveness to nonsteroidal anti-inflammatory drugs. On the other hand, the anti-tumour necrosis factor alpha (TNF-α) treatment has brought benefits to these patients. Thus, this study aimed to evaluate the effect of lumiracoxib, a selective-cyclooxygenase-2 (COX-2) inhibitor, and Etanercept (ETC), a TNF-α antagonist on the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. A total of 47 Wistar rats were randomized into seven groups, as follows: (1) Sham: sham induced-colitis; (2) TNBS: nontreated induced-colitis; (3) Lumiracoxib control; (4) Lumiracoxib-treated induced-colitis; (5) ETC control; (6) ETC-treated induced-colitis; (7) Lumiracoxib-ETC-treated induced-colitis. Rats from groups 6 and 7 presented significant improvement of macroscopic and histopathological damages in the distal colon. The gene expression of COX-2 mRNA, as well of TNF-α mRNA, decreased significantly in groups 6 and 7 compared to the TNBS nontreated and lumiracoxib-treated groups. The treatment only with lumiracoxib did not reduce the inflammation on TNBS-induced experimental colitis. ETC attenuated the damage seen in the colon and reduced the inflammation caused by TNBS. Our results suggest that down-regulation of TNF-α and COX-2 resulted in a decrease in inflammation caused by TNBS and thus provided some protection from the colonic damage caused by TNBS.

  5. Effects of dosmalfate, a new cytoprotective agent, on acute and chronic trinitrobenzene sulphonic acid-induced colitis in rats.

    Science.gov (United States)

    Villegas, Isabel; La Casa, Carmen; Orjales, Aurelio; Alarcón de la Lastra, Catalina

    2003-01-24

    Activated neutrophils and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) are clearly involved in the pathogenesis of bowel disease. Increased expression of epidermal growth factor-receptor (EGF receptor) has been reported for the colon mucosa surrounding areas of ulceration, suggesting a pivotal role in mucosal defence and repair. In this study, we examined the effects of dosmalfate, a new flavonoid derivative compound (diosmin heptakis) with antioxidant and cytoprotective properties, on acute and chronic experimental trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. The inflammation response was assessed by neutrophil infiltration as evaluated by histology and myeloperoxidase activity. Mucosal TNF-alpha production and histological analysis of the lesions was also carried out. In addition, we studied the expression of the EGF receptor inmunohistochemically during the healing of TNBS-induced chronic colitis. A 2-day treatment with 400 or 800 mg/kg of dosmalfate ameliorated the colon damage score and the incidence of adhesions. It also significantly (P<0.05) decreased myeloperoxidase activity and colonic mucosal production of TNF-alpha. Chronic treatment (14 days) with 800 mg/kg/day of dosmalfate also had significant protective effects on TNBS-induced colitis which were reflected by significant attenuation (P<0.05) of the damage score while the inflammatory indicators were not improved. The chronic beneficial effect of dosmalfate was apparently related to the enhancement of EGF receptor expression. These findings confirm the protective effects of dosmalfate in acute and chronic experimental colitis.

  6. Effects of budesonide and probiotics enemas on the systemic inflammatory response of rats with experimental colitis Efeito de enemas contendo budesonida e probióticos na resposta inflamatória sistêmica de ratos com colite experimental

    Directory of Open Access Journals (Sweden)

    Mardem Machado de Souza

    2007-01-01

    Full Text Available PURPOSE: The aim of this study was to investigate the effect of enemas containing probiotics and budesonide on the systemic inflammatory response in experimental colitis. METHODS: Fifty male Wistar rats with experimental colitis induced by 10% acetic acid enema were randomized to five groups (10 rats each according to the treatment: group 1 - saline solution, group 2 - budesonide (0.75 mg/kg/day, group 3 - probiotics (1mg/day, group 4 - probiotics plus budesonide, and group 5 - control, with not-treated rats. The following variables were studied: body weight, serum levels of albumin, C-reactive protein and interleucine-6 (IL-6. RESULTS: All animals lost weight between the beginning and the end of the experiment (280+ 16 mg versus 249+21 mg, p0.05. Only probiotic rats presented a significant decrease of IL-6 than controls (0,30±0,08 mg/dL vs. 0,19±0,03 mg/dL; pOBJETIVO: Investigar o efeito da administração retal de probióticos e budesonida na resposta inflamatória de ratos com colite experimental. MÉTODOS: Cinqüenta ratos Wistar com colite experimental induzida pelo acido acético à 10% foram randomizados em 5 grupos (n=10 por grupo para diferentes tratamentos: grupo 1 - solução fisiológica; grupo 2 budesonida (0,75mg/kg/dia; grupo 3 - probióticos (1 g/dia; grupo 4 - probióticos associados a budesonida; e finalmente grupo 5 - controle, composto por ratos sem tratamento. As seguintes variáveis foram estudadas: peso corporal, dosagens séricas de albumina, proteína C reativa (PCR e interleucina-6 (IL-6. RESULTADOS: Todos os animais perderam peso entre o inicio e o fim do experimento (280±16 vs 249±21g; p0.05. As comparações entre o grupo controle (0,30±0,08 mg/dL e outros mostraram que houve uma queda significante nos níveis de IL-6 apenas no grupo probiótico (0,19±0,03 mg/dL; p<0.01. CONCLUSÃO: Probióticos são efetivos na diminuição do estado inflamatório mediado pela IL-6 na colite experimental.

  7. Effects of budesonide and probiotics enemas on the colonic mucosa of rats with experimental colitis Efeito de enemas contendo budesonida e probióticos na mucosa colonica de ratos com colite experimental

    Directory of Open Access Journals (Sweden)

    Mardem Machado de Souza

    2007-02-01

    Full Text Available PURPOSE: To investigate the effect of enemas containing probiotics and budesonide on the colonic mucosa in experimental colitis. METHODS: Fifty male Wistar rats with experimental colitis induced by 10% acetic acid enema were randomized to five groups (10 rats each according to the treatment: group 1 - saline solution, group 2 - budesonide (0.75 mg/kg/day, group 3 - probiotics (1mg/day, group 4 - probiotics plus budesonide, and group 5 - control, with not-treated rats. The following variables were studied: body weight, macroscopic and microscopic score of the colonic mucosa, and DNA content of the mucosa. RESULTS: All animals lost weight between the beginning and the end of the experiment (280+ 16 mg versus 249+21 mg, pOBJETIVO: Investigar o efeito da administração retal de probióticos e budesonida na mucosa colônica de ratos com colite experimental. MÉTODOS: Cinquenta ratos Wistar com colite experimental induzida pelo ácido acético à 10% foram randomizados em 5 grupos (n=10 por grupo para diferentes tratamentos: grupo 1 - solução fisiológica; grupo 2 - budesonida (0,75mg/kg/dia; grupo 3 - probióticos (1 g/dia; grupo 4 - probióticos associados a budesonida; e finalmente grupo 5 - controle, composto por ratos sem tratamento. As seguintes variáveis foram estudadas: peso corporal, aspecto macroscópico e microscópico da mucosa e conteúdo de DNA da mucosa colônica. RESULTADOS: Todos os animais perderam peso entre o início e o fim do experimento (280±16 vs 249±21g; p<0.001. Não houve diferença estatística significativa entre os grupos em relação a macroscopia e histologia. O grupo budesonida + probiótico apresentou conteúdo de DNA maior que o grupo controle (1,24±0,15 versus 0,92±0,30 g/100g de tecido; p=0,01. CONCLUSÃO: A associação de budesonida com probióticos acelera o trofismo mucoso na colite experimental.

  8. Different atmospheric effects causing FSO link attenuation: experimental results and modelling in Czech Republic

    Science.gov (United States)

    Fiser, Ondrej; Brazda, Vladimir; Wilfert, Otakar

    2015-10-01

    The four year FSO link attenuation measurement concurrently with most important meteorological parameters was performed at our mountain observatory Milesovka. In this contribution we summarize and classify different atmospheric phenomena after the FSO link attenuation quantity. For all particular phenomena the CD curves, typical events and simple dependences on relevant atmospheric parameter(s) are presented. We consider the following phenomena (approximate specific attenuation in dB/km in brackets): 1. Fog and cloud (hundreds dB/km) 2. Rain and snow (tens dB/km) 3. Atmospheric turbulence (unit dB) 4. Clear air attenuation due to water vapour (unit dB or less)

  9. Low molecular weight heparin relieves experimental colitis in mice by downregulating IL-1β and inhibiting syndecan-1 shedding in the intestinal mucosa.

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    Xian-fei Wang

    Full Text Available Low molecular weight heparin (LMWH exhibits anti-inflammatory properties, but its effect on inflammation in colitis remains unclear. This study aimed to evaluate the therapeutic effects of LMWH on dextran sulfate sodium (DSS-induced colitis in mice, in which acute colitis progresses to chronic colitis, and to explore the potential mechanism involved in this process. C57BL/6 mice were randomly divided into control, DSS, and DSS plus LMWH groups (n = 18. Disease activity was scored by a disease activity index (DAI. Histological changes were evaluated by hematoxylin and eosin (HE staining. The mRNA levels of syndecan-1, interleukin (IL-1β, and IL-10 were determined by quantitative reverse transcription polymerase chain reaction. Protein expression of syndecan-1 was detected by immunohistochemistry. The serum syndecan-1 level was examined by a dot immunobinding assay. LMWH ameliorated the disease activity of colitis induced by DSS administration in mice. Colon destruction with the appearance of crypt damage, goblet cell loss, and a larger ulcer was found on day 12 after DSS administration, which was greatly relieved by the treatment of LMWH. LMWH upregulated syndecan-1 expression in the intestinal mucosa and reduced the serum syndecan-1 level on days 12 and 20 after DSS administration (P<0.05 vs. DSS group. In addition, LMWH significantly decreased the expression of both IL-1β and IL-10 mRNA on days 12 and 20 (P<0.05 vs. DSS group. LMWH has therapeutic effects on colitis by downregulating inflammatory cytokines and inhibiting syndecan-1 shedding in the intestinal mucosa.

  10. Experimental colitis in rats induces de novo synthesis of cytokines at distant intestinal sites: role of capsaicin-sensitive primary afferent fibers.

    Science.gov (United States)

    Mourad, Fadi H; Hamdi, Tamim; Barada, Kassem A; Saadé, Nayef E

    2016-06-01

    Increased levels of pro- and anti-inflammatory cytokines were observed in various segments of histologically-intact small intestine in animal models of acute and chronic colitis. Whether these cytokines are produced locally or spread from the inflamed colon is not known. In addition, the role of gut innervation in this upregulation is not fully understood. To examine whether cytokines are produced de novo in the small intestine in two rat models of colitis; and to investigate the role of capsaicin-sensitive primary afferents in the synthesis of these inflammatory cytokines. Colitis was induced by rectal instillation of iodoacetamide (IA) or trinitrobenzene sulphonic acid (TNBS) in adult Sprague-Dawley rats. Using reverse transcriptase (RT) and real-time PCR, TNF-α, and IL-10 mRNA expression was measured in mucosal scrapings of the duodenum, jejunum, ileum and colon at different time intervals after induction of colitis. Capsaicin-sensitive primary afferents (CSPA) were ablated using subcutaneous injections of capsaicin at time 0, 8 and 32 h, and the experiment was repeated at specific time intervals to detect any effect on cytokines expression. TNF-α mRNA expression increased by 3-40 times in the different intestinal segments (pcolitis. CSPA ablation completely inhibited this upregulation in the small intestine, but not in the colon. Similar results were obtained in TNBS-induced colitis at 24 h. Intestinal IL-10 mRNA expression significantly decreased at 12 h and then increased by 6-43 times (pcolitis induction, respectively (both pcolitis induction. Inflammatory cytokines are produced de novo in distant intestinal segments in colitis. CSPA fibers play a key role in the upregulation of this synthesis.

  11. Protective effect of the methanolic extract of malva parviflora l. leaves on acetic acid-induced ulcerative colitis in rats

    Directory of Open Access Journals (Sweden)

    Aisha Dugani

    2016-01-01

    Full Text Available Background/Aims: Inflammatory bowel disease (IBD is a general term describing chronic, idiopathic relapsing, inflammatory conditions of the gastrointestinal tract of unknown etiology. Previous studies have indicated that Malva parviflora leaf extract possesses anti-inflammatory, antioxidant, and antiulcerogenic activity. activity. This work aimed to investigatee the anti-inflammatory effect of the methanolic (MEMP and aqueous (AEMP extracts of M. parviflora leaves on acetic acid-induced colitis in rats. Materials and Methods: 42 male Wistar albino rats were divided into seven groups (n = 6. Group I: Normal saline control group with no colitis; Group II: Acetic acid colitis group; Group III: 100 mg/kg/5 d MEMP; Group IV: 200 mg/kg/5 d.MEMP; Group V: 100 mg/kg/5 d AEMP; Group VI: 200 mg/kg/5 d AEMP; Group VII: Prednisolone group (2 mg/kg/5 d. Treatments were followed by induction of colitis using intrarectal instillation of 2 mL of 4% acetic acid. Colon damage was evaluated macroscopically (spleen weight/body weight, colon weight/length ratio and the histological changes were also recorded. Results: The results of this study showed that acetic acid caused severe inflammation of the colon and a significant increase in spleen weight/body weight, and an increase in colon weight/length ratio compared with normal control group. Pretreatment with MEMP and AEMP for 5 days followed by induction of colitis resulted in a significant attenuation of spleen weight and colon weight/length ratio compared with acetic acid control group. Methanolic extract provided better anticolitic effect than aqueous extract; the effect was prominent at the dose of 200 mg/kg. Histopathological findings confirmed the protective effect of the MEMP. Conclusion: In conclusion, MEMP could ameliorate mucosal damage in experimentally induced colitis when given orally.

  12. Blockade of high mobility group box-1 protein attenuates experimental severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Hidehiro Sawa; Takashi Ueda; Yoshifumi Takeyama; Takeo Yasuda; Makoto Shinzeki; Takahiro Nakajima; Yoshikazu Kuroda

    2006-01-01

    AIM: To examine the effects of anti-high mobility group box 1 (HMGB1) neutralizing antibody in experimental severe acute pancreatitis (SAP).METHODS: SAP was induced by creating closed duodenal loop in C3H/HeN mice. SAP was induced immediately after intraperitoneal injection of anti-HMGB1 neutralizing antibody (200 μg). Severity of pancreatitis, organ injury (liver, kidney and lung), and bacterial translocation to pancreas was examined 12 h after induction of SAP.RESULTS: Anti-HMGB1 neutralizing antibody significantly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAP.Anti-HMGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAP. However, anti-HMGB1 antibody worsened the bacterial translocation to pancreas.CONCLUSION: Blockade of HMGB1 attenuated the development of SAP and associated organ dysfunction,suggesting that HMGB1 may act as a key mediator for inflammatory response and organ injury in SAP.

  13. Experimental Study and Numerical Modeling of Wave Induced Pore Pressure Attenuation Inside a Rubble Mound Breakwater

    DEFF Research Database (Denmark)

    Troch, Peter; Rouck, Julien De; Burcharth, Hans Falk

    2003-01-01

    The main objective of this paper is to study the attenuation of the wave induced pore pressures inside the core of a rubble mound breakwater. The knowledge of the distribution and the attenuation of the pore pressures is important for the design of a stable and safe breakwater. The pore pressure...

  14. O papel do óxido nítrico na pressão anal esfincteriana de ratos submetidos à colite experimental The role of nitric oxide in sphincteric anal pressure of rats with experimental colitis

    Directory of Open Access Journals (Sweden)

    Henrique Sarubbi Fillmann

    2006-12-01

    organism. It presents with an ample specter of physiological actions being the most important its mechanism of action in the relaxation of the smooth musculature, its neurotransmissor activity in some systems and its involvement in the inflammatory process. The NO is synthesized in different tissues by the conversion of the L-arginine in L-citruline with the action of the enzyme nitric oxide sintase(NOS. OBJECTIVES: the aim of this study is to demonstrate the involvement of nitric oxide in the inflammatory intestinal process of Wistar rats submitted to experimental colitis with ascetic acid. MATERIAL AND METHODS: 20 male Wistar rats had been used with weight between 250 and 350 g divided in two groups of 10 animals. The animals of the group in study had been submitted to intracolonic administration, by enema, of a solution with acid ascetic diluted to 7% - 3 ml. The control group received only enema with saline solution. The histological scores, the expression of the enzyme nitric oxide sintase (iNOS and the sphincteric anal pressure had been evaluated. RESULTS: The histological scores had presented a significant rise in the group colitis when compared with the control group in the macroscopic as well as in the microscopical evaluation. The expression of the enzyme iNOS was also significantly higher in the colitis group when compared to the control group. The sphincteric anal pressure was significantly lower in the group colitis when compared to control group. CONCLUSION: The animals submitted to the experimental colitis presented an increase of the iNOS expression. This increase, associated with the consequent increase in nitric oxide level, causes a reduction of the sphincteric anal pressure levels.

  15. Salmonella pseudomembranous colitis.

    Science.gov (United States)

    Beck, Andrew; McNeil, Candice; Abdelsayed, George; Chin-Lue, Roland; Kassis, Simon; Manthous, Constantine A

    2007-01-01

    Pseudomembranous colitis is most often associated with antibiotic use and caused most often by Clostridium difficile. Aclinical syndrome and pathology that is identical can be caused rarely by other organisms. We report a case of Salmonella enterica pseudomembranous colitis and briefly review the literature regarding rare causes of this syndrome.

  16. Ergotamine-induced colitis.

    Science.gov (United States)

    Wörmann, B; Höchter, W; Seib, H J; Ottenjann, R

    1985-07-01

    We report on a 45-year-old woman with ulcerative colitis of the rectum that arose after the use of up to 6 suppositories of a preparation containing ergotamine daily over a period of 6 years. On the basis of a review of the literature the clinical, endoscopic and histological features of the ergotamine-induced colitis are characterized.

  17. Experimental realization of fluence field modulated CT using digital beam attenuation

    Science.gov (United States)

    Szczykutowicz, T. P.; Mistretta, C. A.

    2014-03-01

    Tailoring CT scan acquisition parameters to individual patients is a topic of much research in the CT imaging community. It is now common place to find automatically adjusted tube current options for modern CT scanners. In addition, the use of beam shaping filters, commonly called bowtie filters, is available on most CT systems and allows for different body regions to receive different incident x-ray fluence distributions. However, no method currently exists which allows for the form of the incident x-ray fluence distribution to change as a function of the view angle. This study represents the first experimental realization of fluence field modulated CT (FFMCT) for a c-arm geometry CT scan. X-ray fluence modulation is accomplished using a digital beam attenuator (DBA). The device is composed of ten iron wedge pairs that modulate the thickness of iron, the x-rays must traverse before reaching a patient. Using this device, experimental data was taken using a Siemens Zeego c-arm scanner. Scans were performed on a cylindrical polyethylene phantom and on two different sections of an anthropomorphic phantom. The DBA was used to equalize the x-ray fluence striking the detector for each scan. Non DBA, or ‘flat field’ scans were also acquired of the same phantom objects for comparison. In addition, a scan was performed in which the DBA was used to enable volume of interest (VOI) imaging. In VOI, only a small sub-volume within a patient receives full dose and the rest of the patient receives a much lower dose. Data corrections unique to using a piece-wise constant modulator were also developed. The feasibility of FFMCT implemented using a DBA device has been demonstrated. Initial results suggest dose reductions of up to 3.6 times relative to ‘flat field’ CT. In addition to dose reduction, the DBA enables a large improvement in image noise uniformity and the ability to provide regionally enhanced signal to noise using VOI imaging techniques. The results presented in

  18. Complications of collagenous colitis

    Institute of Scientific and Technical Information of China (English)

    Hugh James Freeman

    2008-01-01

    Microscopic forms of colitis have been described, including collagenous colitis. This disorder generally has an apparently benign clinical course. However, a number of gastric and intestinal complications, possibly coincidental, may develop with collagenous colitis. Distinctive inflammatory disorders of the gastric mucosa have been described, including lymphocytic gastritis and collagenous gastritis. Celiac disease and collagenous sprue (or collagenous enteritis) may occur. Colonic ulceration has been associated with use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, may evolve from collagenous colitis. Submucosal "dissection", colonic fractures or mucosal tears and perforation from air insufflation during colonoscopy may occur and has been hypothesized to be due to compromise of the colonic wall from submucosal collagen deposition. Similar changes may result from increased intraluminal pressure during barium enema contrast studies. Finally, malignant disorders have also been reported, including carcinoma and lymphoproliferative disease.

  19. Theoretical and experimental determination of mass attenuation coefficients of lead-based ceramics and their comparison with simulation

    Directory of Open Access Journals (Sweden)

    Vejdani-Noghreiyan Alireza

    2016-01-01

    Full Text Available Mass attenuation coefficient of lead-based ceramics have been measured by experimental methods and compared with theoretical and Monte Carlo simulation results. Lead-based ceramics were prepared using mixed oxide method and the X-ray diffraction analysis was done to evaluate the crystal structure of the produced handmade ceramics. The experimental results show good agreement with theoretical and simulation results. However at two gamma ray energies, small differences between experimental and theoretical results have been observed. By adding other additives to ceramics and observing the changes in the shielding properties such as flexibility, one can synthesize and optimize ceramics as a neutron shield.

  20. Prevention of Clostridium difficile-induced experimental pseudomembranous colitis by Saccharomyces boulardii: a scanning electron microscopic and microbiological study.

    Science.gov (United States)

    Castex, F; Corthier, G; Jouvert, S; Elmer, G W; Lucas, F; Bastide, M

    1990-06-01

    The ability of Saccharomyces boulardii to protect mice against intestinal pathology caused by toxinogenic Clostridium difficile was studied. Different regions of the intestine of experimental mice were prepared for observation by scanning electron microscopy or homogenized for C. difficile enumeration and quantification of toxin A by enzyme immunoassay and toxin B by cytotoxicity. The test group was treated for 6 d with an S. boulardii suspension in drinking water and challenged with C. difficule on day 4. The three control groups were: axenic mice, mice treated with only S. boulardii and mice only challenged with C. difficile. The results showed that: (i) 70% of the mice infected by C. difficile survived when treated with S. boulardii; (ii) the C. difficile-induced lesions on the small and large intestinal mucosa were absent or markedly less severe in S. boulardii-treated mice; and (iii) there was no decrease in the number of C. difficile but rather a reduction in the amount of toxins A and B in S. boulardii-treated mice.

  1. 实验性结肠炎大鼠树突状细胞表型的变化及黄芪多糖的作用%Modulation of dendritic cells phenotype by Astragalus polysaccharides in experimental colitis in rats

    Institute of Scientific and Technical Information of China (English)

    戴佳原; 高永健; 朱峰

    2011-01-01

    目的 观察黄芪多糖(APS)对2,4,6-三硝基苯磺酸(TNBS)诱导的实验性结肠炎大鼠肠道炎症及树突状细胞(DCs)的作用.方法 44只雄性SD大鼠用简单随机抽样法分为4组(n=11):空白对照组、TNBS模型组、APS治疗组、5-氨基水杨酸(5-ASA)治疗组.除空白对照组外,其余3组均给予TNBS灌肠造模.造模后第2天,APS治疗组和5-ASA治疗组分别给予APS(0.75 g·kg-1·d-1)和5-ASA(100 mg·kg-1·d-1)灌胃治疗10 d.治疗结束后处死大鼠取材.对大鼠结肠炎症进行评估,包括疾病活动指数(DAI)评分、大体形态损伤评分、病理组织学评分和髓过氧化物酶(MPO)活性测定;流式细胞仪检测DCs表面标志MHCⅡ和CD86的表达.结果 APS治疗组较TNBS组大鼠的DAI评分(P=0.007)、大体形态损伤评分(P=0.017)、病理组织学评分(P=0.016)均显著降低,MPO活性亦下降,但差异无统计学意义(P=0.183).TNBS模型组大鼠肠系膜淋巴结DCs表面标志MHC Ⅱ和CD86的表达率较空白对照组(P=0.005,P=0.008)、APS治疗组(P=0.023,P=0.018)及5-ASA治疗组(P=0.017,P=0.013)均显著升高.结论 APS治疗可部分缓解TNBS诱导的大鼠实验性结肠炎,下调肠系膜淋巴结中活化的DCs.%Objective To investigate the effect of Astragalus polysaccharides (APS) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats and on dendritic cells (DCs) in mesenteric lymph nodes.Methods Forty-four male Sprague-Dawley rats were randomly divided into four groups (n = 11) using simple random sampling: normal control group, TNBS group, APS group, and 5-aminosalicylic acid (5-ASA) group.Experimental colitis was induced in rats by TNBS enema in the last three groups.Rats in APS and 5-ASA groups were treated by gavage with APS (0.75 g ? kg-1 ? d-1) and 5-ASA (100 mg ? kg-1 ? d-1) on the 10 consecutive days following TNBS administration.The rats were then sacrificed and the colonic inflammatory scores of rats were measured, including the scores of

  2. Treatment with a Monoclonal Anti-IL-12p40 Antibody Induces Substantial Gut Microbiota Changes in an Experimental Colitis Model

    Directory of Open Access Journals (Sweden)

    Josué Castro-Mejía

    2016-01-01

    Full Text Available Background and Aim. Crohn’s disease is associated with gut microbiota (GM dysbiosis. Treatment with the anti-IL-12p40 monoclonal antibody (12p40-mAb has therapeutic effect in Crohn’s disease patients. This study addresses whether a 12p40-mAb treatment influences gut microbiota (GM composition in mice with adoptive transfer colitis (AdTr-colitis. Methods. AdTr-colitis mice were treated with 12p40-mAb or rat-IgG2a or NaCl from days 21 to 47. Disease was monitored by changes in body weight, stool, endoscopic and histopathology scores, immunohistochemistry, and colonic cytokine/chemokine profiles. GM was characterized through DGGE and 16S rRNA gene-amplicon high-throughput sequencing. Results. Following 12p40-mAb treatment, most clinical and pathological parameters associated with colitis were either reduced or absent. GM was shifted towards a higher Firmicutes-to-Bacteroidetes ratio compared to rat-IgG2a treated mice. Significant correlations between 17 bacterial genera and biological markers were found. The relative abundances of the RF32 order (Alphaproteobacteria and Akkermansia muciniphila were positively correlated with damaged histopathology and colonic inflammation. Conclusions. Shifts in GM distribution were observed with clinical response to 12p40-mAb treatment, whereas specific GM members correlated with colitis symptoms. Our study implicates that specific changes in GM may be connected with positive clinical outcomes and suggests preventing or correcting GM dysbiosis as a treatment goal in inflammatory bowel disease.

  3. Sijunzi Decoction attenuates 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats and ameliorates TNBS-induced claudin-2 damage via NF-κB pathway in Caco2 cells

    OpenAIRE

    Lu, Yue; Lin, HanJie; Zhang, Jinwei; Wei, JianAn; Jing SUN; Han, Ling

    2017-01-01

    Background SijunziDecoction (SJZD) is a traditional Chinese medicine prescription used to treat the diseases of gastrointestinal tract since ancient times. The objective of this study was to investigate the protective effects of SJZD on TNBS-induced colitis in rats and TNBS-damaged Caco2 cells. Methods The rat colitis model was induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). SJZD (2.8 5.6, 11.2 g/kg) or salazosulfapyridine (SASP) (0.4 g/kg) was administrated orally in rats for 7 days...

  4. Asparagus racemosus attenuates anxiety-like behavior in experimental animal models.

    Science.gov (United States)

    Garabadu, Debapriya; Krishnamurthy, Sairam

    2014-05-01

    Asparagus racemosus Linn. (AR) is used worldwide as a medicinal plant. In the present study, the anxiolytic activity of standardized methanolic extract of root of AR (MAR) was evaluated in open-field test (OFT), hole-board, and elevated plus maze (EPM) tests. Rats received oral pretreatment of MAR in the doses of 50, 100, and 200 mg/kg daily for 7 days and then were evaluated for the anxiolytic activity in different animal models. Both MAR (100 and 200 mg/kg) and diazepam (1 mg/kg, p.o.) increased the grooming behavior, number of central squares crossed, and time spent in the central area during OFT. Further, MAR (100 and 200 mg/kg) increased the head-dip and head-dip/sniffing behavior, and decreased sniffing activity in hole-board test. Furthermore, MAR (100 and 200 mg/kg) increased the percentage entries and time spent to open arm in EPM test paradigm. The anxiolytic activity in the experimental models was similar to that of diazepam. MAR (100 and 200 mg/kg) enhanced the level of amygdalar serotonin and norepinephrine. It also increased the expression of 5-HT2A receptors in the amygdala. In another set of experiment, flumazenil attenuated the anxiolytic effect of minimum effective dose of MAR (100 mg/kg) in OFT, hole-board, and EPM tests, indicating GABAA-mediated mechanism. Moreover, the anxiolytic dose of MAR did not show sedative-like effect in OFT and EPM tests compared to diazepam (6 mg/kg, p.o.). Thus, the anxiolytic response of MAR may involve GABA and serotonergic mechanisms. These preclinical data show that AR can be a potential agent for treatment of anxiety disorders.

  5. Photon attenuation coefficients of Heavy-Metal Oxide glasses by MCNP code, XCOM program and experimental data: A comparison study

    Science.gov (United States)

    El-Khayatt, A. M.; Ali, A. M.; Singh, Vishwanath P.

    2014-01-01

    The mass attenuation coefficients, μ/ρ, total interaction cross-section, σt, and mean free path (MFP) of some Heavy Metal Oxides (HMO) glasses, with potential applications as gamma ray shielding materials, have been investigated using the MCNP-4C code. Appreciable variations are noted for all parameters by changing the photon energy and the chemical composition of HMO glasses. The numerical simulations parameters are compared with experimental data wherever possible. Comparisons are also made with predictions from the XCOM program in the energy region from 1 keV to 100 MeV. Good agreement noticed indicates that the chosen Monte Carlo method may be employed to make additional calculations on the photon attenuation characteristics of different glass systems, a capability particularly useful in cases where no analogous experimental data exist.

  6. Surgery for Crohn's Disease and Ulcerative Colitis

    Science.gov (United States)

    ... Crohn's Disease & Ulcerative Colitis Go Back Surgery for Crohn's Disease & Ulcerative Colitis Email Print + Share ( Disclaimer: Surgery information ... helps you to learn what to expect. About Crohn’s disease and ulcerative colitis Crohn’s disease and ulcerative colitis ...

  7. Protective effect of simvastatin and rosuvastatin on trinitrobenzene sulfonic acid-induced colitis in rats

    Directory of Open Access Journals (Sweden)

    Rajesh A Maheshwari

    2015-01-01

    Conclusions: These results suggest that simvastatin and rosuvastatin significantly ameliorate experimental colitis in rats, and these effects could be explained by their anti-inflammatory and antioxidant activity.

  8. Pathogenesis of TNBS-induced Experimental Colitis in Rats%TNBS诱导大鼠实验性结肠炎的致病机制

    Institute of Scientific and Technical Information of China (English)

    张夏毅; 沈霖; 范恒; 梁丽; 廖奕

    2011-01-01

    目的 探讨三硝基苯磺酸(TNBS)诱导大鼠实验性结肠炎的致病机制.方法 18只雄性SD大鼠随机分为3组,每组6只:正常组、模型组、美沙拉嗪组.除正常对照组未行造模外,其余两组大鼠均采用TNBS造模.模型组不设干预,正常饮食;美沙拉嗪组给予美沙拉嗪混悬液0.42 g/(kg·d)灌胃;治疗15 d后观察大鼠的结肠病理组织学改变,用免疫组化染色法观察大鼠结肠组织IL-17、β2AR、β-arrestin2、NF-κBp65的表达;用Western blot法检测大鼠脾淋巴细胞β2AR,β-arrestin2和NF-κBp65蛋白的表达;用RT-PCR法检测大鼠结肠组织STAT6 mRNA的表达.结果 美沙拉嗪组大鼠的腹泻、黏液脓血便症状得到较快改善,大鼠黏膜组织损伤也明显改善.与正常组相比,模型组大鼠NF-κBp65和STAT6 mRNA表达增多(P<0.01),β2AR和β-arrestin2的表达减少(P<0.01);与模型组比较,美沙拉嗪组大鼠脾淋巴细胞NF-κBp65和STAT6 mRNA表达减少(P<0.01),而β2AR和β-arrestin2的表达增多(P<0.01).IL-17在正常组和美沙拉嗪组呈低表达,而在模型组呈高表达.结论 IL-17、β2AR、β-arrestin2、NF-κBp65、STAT6在TNBS诱导大鼠实验性结肠炎的致病过程中发挥重要调节作用.%Objective To explore the pathogenesis of TNBSinduced experimental colitis in rats. Methods Fighteen male rats were randomly assigned to the following groups(n= 6 each) : mesalazine group, model group, control group. The rats were induced by trinitrobenzene sulfonic acid(TNBS)in model group and mesalazine group. The rats in mesalazine group were given mesalazine(0. 42 g/kg body weight every day) through intragastric administration for 15 days. The expression of 1L-17 ,β2AR, β-arrestin2 and NF-κBp65 in ulcerative colonic tissue was observed by immunohistochemical staining. The expression of β2AR, β-arrestin and NF-κBp65 in spleen lymphocytes was analyzed by Western blot. The expression level of STAT6 mRNA in colonic tissue was

  9. The C-type lectin receptor SIGNR3 binds to fungi present in commensal microbiota and influences immune regulation in experimental colitis

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    Magdalena eEriksson

    2013-07-01

    Full Text Available Inflammatory bowel disease is a condition of acute and chronic inflammation of the gut. An important factor contributing to pathogenesis is a dysregulated mucosal immunity against commensal bacteria and fungi. Host pattern recognition receptors sense commensals in the gut and are involved in maintaining the balance between controlled responses to pathogens and overwhelming innate immune activation. C-type lectin receptors (CLRs are pattern recognition receptors recognizing glycan structures on pathogens and self-antigens. Here we examined the role of the murine CLR SIGNR3 in the recognition of commensals and its involvement in intestinal immunity. SIGNR3 is the closest murine homologue of the human DC-SIGN receptor recognizing similar carbohydrate ligands such as terminal fucose or high-mannose glycans. We discovered that SIGNR3 recognizes fungi present in the commensal microbiota. To analyze if this interaction impacts the intestinal immunity against microbiota, the dextran sulfate sodium (DSS-induced colitis model was employed. SIGNR3-/- mice exhibited an increased weight loss associated with more severe colitis symptoms compared to wild-type control mice. The increased inflammation in SIGNR3-/- mice was accompanied by a higher level of TNF-α in colon. Our findings demonstrate for the first time that SIGNR3 recognizes intestinal fungi and has an immune regulatory role in colitis.

  10. Involvement of 5HT3 Receptors in Anti-Inflammatory Effects of Tropisetron on Experimental TNBS-Induced Colitis in Rat

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    Azadeh Motavallian

    2013-12-01

    Full Text Available Introduction: There is a pressing need for research leading to the development of new effective drugs with lower side effects and more efficacy for treating inflammatory bowel disease (IBD. The analgesic and anti-inflammatory properties of 5-Hydroxytryptamine (5-HT-3 receptor antagonists have been shown in in vivo and in vitro studies. The present study was designed to investigate the effects of tropisetron, a 5-HT3 receptor antagonist, on an immune-based animal model of IBD. Methods: In the present study, the trinitrobenzenesulfonic acid (TNBS model of colitis in the rat was used. Two hours after induction of colitis in rats, tropisetron (2 mg/kg, dexamethasone (1 mg/kg, meta-chlorophenylbiguanide (mCPBG, 5 mg/kg, a 5-HT3 receptor agonist, or tropisetron + mCPBG were intraperitoneally (i.p. administrated for 6 days. Animals were then sacrificed; macroscopic, histological, biochemical (myeloperoxidase [MPO] assessments and ELISA test (tumor necrosis factor-alpha, interleukin-6 and interleukin-1 beta were performed on distal colon samples. Results: Tropisetron or dexamethasone treatment significantly reduced macroscopic and microscopic colonic damages. In addition, a significant reduction in MPO activity and colonic levels of inflammatory cytokines was seen. The beneficial effects of tropisetron were antagonized by concurrent administration of mCPBG. Conclusion: The present study indicates that the protective effects of tropisetron on TNBS-induced colitis can be mediated by 5-HT3 receptors.

  11. Experimental determination of B R-12 attenuation coefficients utilizing photon spectrometry;Deteminacao experimental de coeficientes de atenuacao de BR-12 atraves de espectrometria de fotons

    Energy Technology Data Exchange (ETDEWEB)

    Almeida Junior, Jose N.; Terini, Ricardo A. [Pontificia Universidade Catolica de Sao Paulo (PUC-SP), Sao Paulo, SP (Brazil). Dept. de Fisica; Herdade, Silvio B. [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Eletrotecnica e Energia (IEE). Secao Tecnica de Desenvolvimento Tecnologico em Saude

    2009-07-01

    In tests for quality assurance in mammography, it is common to use breast phantoms, with different compositions. One of the most used is the BR-12 phantom. There are few published experimental data on the attenuation of BR-12. Generally, the available attenuation coefficients are calculated from the composition of the coefficients determined for its components. In this work, the spectrometric method was used, with a CdTe detector, for X- and {gamma}-rays from radioactive sources of {sup 133}Ba and {sup 241}Am. The spectra of direct and attenuated by 0.5 cm of BR-12 beams were measured. From the ratio of intensities obtained for these radiations, it was possible to determine values of the attenuation coefficients from Beer's law. Results show coherence with previous data. The values of such coefficients are useful, for example, for calculations of absorbed dose (in BR-12), which have been made on other research activities of this group. (author)

  12. Lubiprostone induced ischemic colitis.

    Science.gov (United States)

    Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

    2013-01-14

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.

  13. Numerical and Experimental Study of Impulsive Sound Attenuation of an Earmuff

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    Felipe Vergara

    2002-01-01

    Full Text Available This work compares the results of laboratory experiments with numerical modelling using the finite element method in order to assess the attenuation of hearing protectors under conditions of high amplitude impulse noise. Comparative data for the finite element simulation was provided from a series of experiments using a shock tube, acoustic test fixture, ear canal simulator and partial head form. The numerical model comprised a finite element mesh of fluid and porous materials in order to model the earmuff hearing protector coupled to the auditory canal. The results show that a simple 2-D finite element model is capable of making a reasonable prediction of the attenuation of an earmuff provided that headband force is also included in the model.

  14. Experimental Studies of Microwave Reflection and Attenuation by Plasmas Produced by Burning Chemicals in Atmosphere

    Institute of Scientific and Technical Information of China (English)

    YUAN Zhongcai; SHI Jiaming; WANG Jiachun

    2007-01-01

    A series of chemicals are designed and prepared.With the method of thermodynamics,the average electron densities of the plasmas generated by burning chemicals are calculated.The reflection and attenuation of the microwaves,in a frequency band of 2 GHz to 15 GHz,by the plasma are measured.The results of measurements indicate that the plasma can absorb the energies of the microwaves in a broad band and reflect them faintly.Moreover,theoretical discussion reveals that the electron-neutral collision is the major factor that results in the absorption in the wide band.By using Appleton equations,average collision frequencies and electron densities are calculated from the attenuations of microwaves.

  15. Amebic and cytomegalovirus colitis mimic ulcerative colitis

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    Meng-Tzu Weng

    2016-06-01

    Full Text Available Here we present a 50-year-old man who suffered from progressively bloody diarrhea for 2 months. A colonoscopy revealed pancolonic mucosal inflammation, ulceration, and spontaneous bleeding. Ulcerative colitis was initially diagnosed and sulfasalazine was prescribed. Hypoalbuminemia and renal function deterioration developed 1 year later. Steroids were prescribed for suspected nephrotic syndrome. His bloody diarrhea and abdominal symptoms worsened after steroid use. Progressive sepsis and acute renal function deterioration also developed. Positive human immunodeficiency virus (HIV antibody was found during routine hemodialysis screening. An episode of colon perforation occurred and surgery was performed. The resected colon showed amoeba, cytomegalovirus, and fungal infection. The patient died of sepsis. In this report, we discuss how to diagnose ulcerative colitis. It is important to exclude infection before using an immunosuppressive agent.

  16. Non-IBD and noninfectious colitis

    DEFF Research Database (Denmark)

    Nielsen, O.H.; Vainer, B.; Rask-Madsen, J.

    2008-01-01

    A wide range of etiologies and pathogenic mechanisms underlie colitis. This Review provides and overview of the pathophysiology, epidemiology, histopathology, and clinical characteristics of noninfectious and non-IBD forms of colitis: microscopic colitis, Behcet's syndrome, diversion colitis......, diverticular colitis, eosinophilic colitis, ischemic colitis, and radiation colitis. These more recently characterized and rare forms of colitis occur as either primary conditions or complications of other diseases. Most of these diseases are uncommon; therefore, epidemiologic data and data from controlled...... trials are not readily available. Practical guidelines for the diagnosis and therapy of these more recently characterized and rarer forms of colitis are given where possible Udgivelsesdato: 2008/1...

  17. Non-IBD and noninfectious colitis

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Vainer, Ben; Rask-Madsen, Jørgen

    2008-01-01

    A wide range of etiologies and pathogenic mechanisms underlie colitis. This Review provides an overview of the pathophysiology, epidemiology, histopathology, and clinical characteristics of noninfectious and non-IBD forms of colitis: microscopic colitis, Behçet's syndrome, diversion colitis......, diverticular colitis, eosinophilic colitis, ischemic colitis, and radiation colitis. These more recently characterized and rare forms of colitis occur as either primary conditions or complications of other diseases. Most of these diseases are uncommon; therefore, epidemiologic data and data from controlled...... trials are not readily available. Practical guidelines for the diagnosis and therapy of these more recently characterized and rarer forms of colitis are given where possible....

  18. Pseudomembranous colitis in cystic fibrosis.

    Science.gov (United States)

    Nagakumar, Prasad

    2013-05-01

    Cystic fibrosis (CF) patients may require frequent courses of antibiotics and repeated hospital admissions. Although children with CF have high carriage rate for C.difficile, they rarely develop colitis. Pseudomembranous colitis is more common in adult post lung transplant CF patients. Although rare, paseudomembranous colitis should be considered in CF patients presenting with abdominal symptoms even in the absence of diarrhoea.

  19. Attenuation of oxidative stress and cardioprotective effects of zinc supplementation in experimental diabetic rats.

    Science.gov (United States)

    Barman, Susmita; Srinivasan, Krishnapura

    2017-03-01

    Oxidative stress plays a major role in the pathogenesis of diabetes mellitus, which further exacerbates damage of cardiac, hepatic and other tissues. We have recently reported that Zn supplementation beneficially modulates hyperglycaemia and hypoinsulinaemia, with attendant reduction of associated metabolic abnormalities in diabetic rats. The present study assessed the potential of Zn supplementation in modulating oxidative stress and cardioprotective effects in diabetic rats. Diabetes was induced in Wistar rats with streptozotocin, and groups of diabetic rats were treated with 5- and 10-fold dietary Zn interventions (0·19 and 0·38 g Zn/kg diet) for 6 weeks. The markers of oxidative stress, antioxidant enzyme activities and concentrations of antioxidant molecules, lipid profile, and expressions of fibrosis and pro-apoptotic factors in the cardiac tissue were particularly assessed. Supplemental Zn showed significant attenuation of diabetes-induced oxidative stress in terms of altered antioxidant enzyme activities and increased the concentrations of antioxidant molecules. Hypercholesterolaemia and hyperlipidaemia were also significantly countered by Zn supplementation. Along with attenuated oxidative stress, Zn supplementation also showed significant cardioprotective effects by altering the mRNA expressions of fibrosis and pro-apoptotic factors (by >50 %). The expression of lipid oxidative marker 4-hydroxy-2-nonenal (4-HNE) protein in cardiac tissue of diabetic animals was rectified (68 %) by Zn supplementation. Elevated cardiac and hepatic markers in circulation and pathological abnormalities in cardiac and hepatic tissue architecture of diabetic animals were ameliorated by dietary Zn intervention. The present study indicates that Zn supplementation can attenuate diabetes-induced oxidative stress in circulation as well as in cardiac and hepatic tissues.

  20. Stem cells transplantation for experimental colitis in rats%干细胞移植对大鼠实验性结肠炎的研究

    Institute of Scientific and Technical Information of China (English)

    李瑜元; 聂玉强; 赖洁莹; 段进粮; 魏亚明; 杜艳蕾; 沙卫红; 周永健

    2008-01-01

    Objective To investigate the effect of transplantation of allogeneic bone marrow hematopoietic cells(HCs)and mesenchymal stem cells(MSCs)on experimental colitis(EC)in rats.Methods The HCs and MSCs obtained from SD male rats were cultured and expanded in vitro.In experiment 1 and 2 groups,HCs were labeled with bromodeoxyuridine(BrdU)and MSCs were obtained using the tube wall attach technique,respectively.Seventy-two female rats were infused with trinitrobenzene sulfonic acid(TNBS)to induce EC models.After 24 hours,HC or MSC suspensions were injected into the rats in experimental 1(n=18)and 2(n=18)groups via caudal veins,respectively.Control animals were injected with isotonic saline.The whole colon was removed on day 7,14 and 21 after transplantation and examined histopathologically.BrdU labeled HCs were tested with immunohistochemical staining and MSCs were detected for sex-determining gene(sry)by PCR.Results EC models were successfully established.The HCs or MSCs grew rapidly in the culture suspension.On day 7,14 and 21 after transplantation,the BrdU immunoreactive cells were detected in the colon(6/6),and the positive expression of the sry gene was found in 1/6,2/6 and 3/6,respectively.No positive labeled cell was found in controls.There was no significant improvement in histopathological scores on the colon in two experimental groups compared with the controls.Conclusions Allogeneic HCs and MSCs may localize in the colon of EC models.The ability of localization is higher in HCs than MSCs.The transplantation of HCs and MSCs can not obviously improve histopathologically.%目的 探讨异体骨髓造血干细胞(HC)和间充质干细胞(MSC)移植对大鼠实验性结肠炎(EC)的作用.方法 体外分别传代培养雄性大鼠的MSC和HC备用.实验1组的HC悬液以5-溴-2-脱氧尿嘧啶(BrdU)标记;实验2组用贴壁法获得MSC.72只雌性大鼠用三硝基苯磺酸灌肠法建立EC模型,造模后24 h,实验1组和实验2组经尾静脉

  1. Protection from experimental cerebral malaria with a single dose of radiation-attenuated, blood-stage Plasmodium berghei parasites.

    Directory of Open Access Journals (Sweden)

    Noel J Gerald

    Full Text Available BACKGROUND: Whole malaria parasites are highly effective in inducing immunity against malaria. Due to the limited success of subunit based vaccines in clinical studies, there has been a renewed interest in whole parasite-based malaria vaccines. Apart from attenuated sporozoites, there have also been efforts to use live asexual stage parasites as vaccine immunogens. METHODOLOGY AND RESULTS: We used radiation exposure to attenuate the highly virulent asexual blood stages of the murine malaria parasite P. berghei to a non-replicable, avirulent form. We tested the ability of the attenuated blood stage parasites to induce immunity to parasitemia and the symptoms of severe malaria disease. Depending on the mouse genetic background, a single high dose immunization without adjuvant protected mice from parasitemia and severe disease (CD1 mice or from experimental cerebral malaria (ECM (C57BL/6 mice. A low dose immunization did not protect against parasitemia or severe disease in either model after one or two immunizations. The protection from ECM was associated with a parasite specific antibody response and also with a lower level of splenic parasite-specific IFN-γ production, which is a mediator of ECM pathology in C57BL/6 mice. Surprisingly, there was no difference in the sequestration of CD8+ T cells and CD45+ CD11b+ macrophages in the brains of immunized, ECM-protected mice. CONCLUSIONS: This report further demonstrates the effectiveness of a whole parasite blood-stage vaccine in inducing immunity to malaria and explicitly demonstrates its effectiveness against ECM, the most pathogenic consequence of malaria infection. This experimental model will be important to explore the formulation of whole parasite blood-stage vaccines against malaria and to investigate the immune mechanisms that mediate protection against parasitemia and cerebral malaria.

  2. Ulcerative colitis in infancy

    Directory of Open Access Journals (Sweden)

    Md Rukunuzzaman

    2011-01-01

    Full Text Available Ulcerative colitis (UC is a chronic idiopathic inflammatory disorder of colon. Frequency of UC is gradually increasing over few years worldwide. Prevalence is 35 to 100/100 000 people in USA, 1% of them are infants. UC develops in a genetically predisposed individual with altered intestinal immune response. An eight-month-old girl presented with loose bloody stool, growth failure, and moderate pallor. The girl was diagnosed as a case of UC by colonoscopy and biopsy. Treatment was thereafter started with immunosuppressive drugs. After initial induction therapy with parenteral steroid and infliximab, the patient is now on remission with azathioprine and mesalamine. UC is rare in Bangladesh, especially in children, and it is rarer during infancy. Several conditions like infective colitis, allergic colitis, Meckel′s diverticulitis, Crohn′s disease, etc. may mimic the features of UC. So, if a child presents with recurrent bloody diarrhea, UC should be considered as differential diagnosis.

  3. Eosinophilic colitis in infants

    Directory of Open Access Journals (Sweden)

    Adriana Chebar Lozinsky

    2014-01-01

    Full Text Available OBJECTIVE: To review the literature for clinical data on infants with allergic or eosinophilic colitis. DATA SOURCE: MEDLINE search of all indexes was performed using the words ''colitis or procto-colitis and eosinophilic'' or ''colitis or proctocolitis and allergic'' between 1966 and February of 2013. All articles that described patients' characteristics were selected. DATA SYNTHESIS: A total of 770 articles were identified, of which 32 met the inclusion criteria. The 32 articles included a total of 314 infants. According to the available information, 61.6% of infants were male and 78.6% were younger than 6 months. Of the 314 patients, 49.0% were fed exclusively breast milk, 44.2% received cow's milk protein, and 6.8% received soy protein. Diarrheal stools were described in 28.3% of patients. Eosinophilia was found in 43.8% (115/263 of infants. Colonic or rectal biopsy showed infiltration by eosinophils (between 5 and 25 perhigh-power field in 89.3% (236/264 of patients. Most patients showed improvement with theremoval of the protein in cow's milk from their diet or the mother's diet. Allergy challenge tests with cow's milk protein were cited by 12 of the 32 articles (66 patients. CONCLUSIONS: Eosinophilic colitis occurs predominantly in the first six months of life and in males. Allergy to cow's milk was considered the main cause of eosinophilic colitis. Exclusion of cow'smilk from the diet of the lactating mother or from the infant's diet is generally an effective therapeutic measure.

  4. B-Cell Depletion Attenuates White and Gray Matter Pathology in Marmoset Experimental Autoimmune Encephalomyelitis

    NARCIS (Netherlands)

    Kap, Yolanda S.; Bauer, Jan; van Driel, Nikki; Bleeker, Wim K.; Parren, Paul W. H. I.; Kooi, Evert-Jan; Geurts, Jeroen J. G.; Laman, Jon D.; Craigen, Jenny L.; Blezer, Erwin; 't Hart, Bert A.

    2011-01-01

    This study investigated the effect of CD20-positive B-cell depletion on central nervous system (CNS) white and gray matter pathology in experimental autoimmune encephalomyelitis in common marmosets, a relevant preclinical model of multiple sclerosis. Experimental autoimmune encephalomyelitis was ind

  5. Intestinal anti-inflammatory effects of RGD-functionalized silk fibroin nanoparticles in trinitrobenzenesulfonic acid-induced experimental colitis in rats

    Directory of Open Access Journals (Sweden)

    Rodriguez-Nogales A

    2016-11-01

    Full Text Available Alba Rodriguez-Nogales,1 Francesca Algieri,1 Laura De Matteis,2 A. Abel Lozano-Perez,3 Jose Garrido-Mesa,1 Teresa Vezza,1 J M. de la Fuente,2 Jose Luis Cenis,3 Julio Gálvez,1,* Maria Elena Rodriguez-Cabezas1,* 1CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research, University of Granada, Granada, 2Instituto de Nanociencia de Aragón, Universidad de Zaragoza, Zaragoza, 3Department of Biotechnology, Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario, Murcia, Spain *These authors contributed equally to this work Background: Current treatment of inflammatory bowel disease is based on the use of immunosuppressants or anti-inflammatory drugs, which are characterized by important side effects that can limit their use. Previous research has been performed by administering these drugs as nanoparticles that target the ulcerated intestinal regions and increase their bioavailability. It has been reported that silk fibroin can act as a drug carrier and shows anti-inflammatory properties. Purpose: This study was designed to enhance the interaction of the silk fibroin nanoparticles (SFNs with the injured intestinal tissue by functionalizing them with the peptide motif RGD (arginine–glycine–aspartic acid and to evaluate the intestinal anti-inflammatory properties of these RGD-functionalized silk fibroin nanoparticles (RGD-SFNs in the trinitrobenzenesulfonic acid (TNBS model of rat colitis. Materials and methods: SFNs were prepared by nanoprecipitation in methanol, and the linear RGD peptide was linked to SFNs using glutaraldehyde as the crosslinker. The SFNs (1 mg/rat and RGD-SFNs (1 mg/rat were administered intrarectally to TNBS-induced colitic rats for 7 days. Results: The SFN treatments ameliorated the colonic damage, reduced neutrophil infiltration, and improved the compromised oxidative status of the colon. However, only the rats treated with RGD-SFNs showed a significant reduction in the

  6. Rapamycin attenuates mitochondrial dysfunction via activation of mitophagy in experimental ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qiang [Department of Neurology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China); Department of Neurology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Zhang, Ting [Department of Neurology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China); Wang, Jixian [Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030 (China); Zhang, Zhijun [Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030 (China); Zhai, Yu [Department of Neurology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Yang, Guo-Yuan, E-mail: gyyang0626@gmail.com [Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030 (China); Sun, Xiaojiang, E-mail: sunxj19@gmail.com [Department of Neurology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China)

    2014-02-07

    Highlights: • Rapamycin enhances mitophagy via increasing p62 translocation to the mitochondria. • Rapamycin attenuates brain ischemic damage and improves mitochondrial function. • The protection of rapamycin to mitochondrial is linked to enhanced mitophagy. - Abstract: Rapamycin has been demonstrated to exhibit neuroprotective functions via the activation of autophagy in a cerebral ischemia model. However, the involvement of mitophagy in this process and its contribution to the protection of mitochondrial function remains unknown. The present study explored the characteristics of mitophagy after cerebral ischemia and the effect of rapamycin on mitochondrial function. Male Sprague–Dawley rats underwent transient middle cerebral artery occlusion (tMCAO). Neurological deficits scores; infarct volumes; mitophagy morphology; and the levels of malondialdehyde (MDA), adenosine triphosphate (ATP) and mitochondrial membrane potentials (Δψm) were examined. The expression of LC3, Beclin-1 and p62 in the mitochondrial fraction combined with transmission electronic microscopy were used to explore mitophagic activity after ischemia. We also blocked autophagosome formation using 3-methyladenine (3-MA) to check the linkage between the mitochondrial protective effect of rapamycin and enhanced mitophagy. We observed that rapamycin significantly enhanced mitophagy, as evidenced by the increase in LC3-II and Beclin-1 expression in the mitochondria and p62 translocation to the mitochondria. Rapamycin reduced infarct volume, improved neurological outcomes and inhibited mitochondrial dysfunction compared with the control animals (p < 0.05). However, these protective effects were reversed by 3-methyladenine treatment after rapamycin. The present study indicates that rapamycin treatment attenuates mitochondrial dysfunction following cerebral ischemia, which is linked to enhanced mitophagy.

  7. Intestinal anti-inflammatory effects of RGD-functionalized silk fibroin nanoparticles in trinitrobenzenesulfonic acid-induced experimental colitis in rats

    Science.gov (United States)

    Rodriguez-Nogales, Alba; Algieri, Francesca; De Matteis, Laura; Lozano-Perez, A. Abel; Garrido-Mesa, Jose; Vezza, Teresa; de la Fuente, J M.; Cenis, Jose Luis; Gálvez, Julio; Rodriguez-Cabezas, Maria Elena

    2016-01-01

    Background Current treatment of inflammatory bowel disease is based on the use of immunosuppressants or anti-inflammatory drugs, which are characterized by important side effects that can limit their use. Previous research has been performed by administering these drugs as nanoparticles that target the ulcerated intestinal regions and increase their bioavailability. It has been reported that silk fibroin can act as a drug carrier and shows anti-inflammatory properties. Purpose This study was designed to enhance the interaction of the silk fibroin nanoparticles (SFNs) with the injured intestinal tissue by functionalizing them with the peptide motif RGD (arginine–glycine–aspartic acid) and to evaluate the intestinal anti-inflammatory properties of these RGD-functionalized silk fibroin nanoparticles (RGD-SFNs) in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. Materials and methods SFNs were prepared by nanoprecipitation in methanol, and the linear RGD peptide was linked to SFNs using glutaraldehyde as the crosslinker. The SFNs (1 mg/rat) and RGD-SFNs (1 mg/rat) were administered intrarectally to TNBS-induced colitic rats for 7 days. Results The SFN treatments ameliorated the colonic damage, reduced neutrophil infiltration, and improved the compromised oxidative status of the colon. However, only the rats treated with RGD-SFNs showed a significant reduction in the expression of different pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, and IL-12) and inducible nitric oxide synthase in comparison with the TNBS control group. Moreover, the expression of both cytokine-induced neutrophil chemoattractant-1 and monocyte chemotactic protein-1 was significantly diminished by the RGD-SFN treatment. However, both treatments improved the intestinal wall integrity by increasing the gene expression of some of its markers (trefoil factor-3 and mucins). Conclusion SFNs displayed intestinal anti-inflammatory properties in the TNBS model of colitis in rats

  8. Experimental and numerical investigation of the 3D SPECT photon detection kernel for non-uniform attenuating media

    Science.gov (United States)

    Riauka, Terence A.; Hooper, H. Richard; Gortel, Zbigniew W.

    1996-07-01

    Experimental tests for non-uniform attenuating media are performed to validate theoretical expressions for the photon detection kernel, obtained from a recently proposed analytical theory of photon propagation and detection for SPECT. The theoretical multi-dimensional integral expressions for the photon detection kernel, which are computed numerically, describe the probability that a photon emitted from a given source voxel will trigger detection of a photon at a particular projection pixel. The experiments were performed using a cylindrical water-filled phantom with large cylindrical air-filled inserts to simulate inhomogeneity of the medium. A point-like, a short thin cylindrical and a large cylindrical radiation source of were placed at various positions within the phantom. The values numerically calculated from the theoretical kernel expressions are in very good agreement with the experimentally measured data. The significance of Compton-scattered photons in planar image formation is discussed and highlighted by these results. Using both experimental measurements and the calculated values obtained from the theory, the kernel's size is investigated. This is done by determining the square pixel neighbourhood of the gamma camera that must be connected to a particular radiation source voxel to account for a specific fraction of all counts recorded at all camera pixels. It is shown that the kernel's size is primarily dependent upon the source position and the properties of the attenuating medium through Compton scattering events, with 3D depth-dependent collimator resolution playing an important but secondary role, at least for imaging situations involving parallel hole collimation. By considering small point-like sources within a non-uniform elliptical phantom, approximating the human thorax, it is demonstrated that on average a area of the camera plane is required to collect 85% of the total count recorded. This is a significantly larger connectivity than the area

  9. Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea.

    LENUS (Irish Health Repository)

    Ward, Joseph B J

    2012-02-01

    Hydroxylases are oxygen-sensing enzymes that regulate cellular responses to hypoxia. Transepithelial Cl(-) secretion, the driving force for fluid secretion, is dependent on O(2) availability for generation of cellular energy. Here, we investigated the role of hydroxylases in regulating epithelial secretion and the potential for targeting these enzymes in treatment of diarrheal disorders. Ion transport was measured as short-circuit current changes across voltage-clamped monolayers of T(84) cells and mouse colon. The antidiarrheal efficacy of dimethyloxallyl glycine (DMOG) was tested in a mouse model of allergic disease. Hydroxylase inhibition with DMOG attenuated Ca(2+)- and cAMP-dependent secretory responses in voltage-clamped T(84) cells to 20.2 +\\/- 2.6 and 38.8 +\\/- 6.7% (n=16; P<\\/=0.001) of those in control cells, respectively. Antisecretory actions of DMOG were time and concentration dependent, being maximal after 18 h of DMOG (1 mM) treatment. DMOG specifically inhibited Na(+)\\/K(+)-ATPase pump activity without altering its expression or membrane localization. In mice, DMOG inhibited agonist-induced secretory responses ex vivo and prevented allergic diarrhea in vivo. In conclusion, hydroxylases are important regulators of epithelial Cl(-) and fluid secretion and present a promising target for development of new drugs to treat transport disorders.

  10. Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea.

    LENUS (Irish Health Repository)

    Ward, Joseph B J

    2011-02-01

    Hydroxylases are oxygen-sensing enzymes that regulate cellular responses to hypoxia. Transepithelial Cl(-) secretion, the driving force for fluid secretion, is dependent on O(2) availability for generation of cellular energy. Here, we investigated the role of hydroxylases in regulating epithelial secretion and the potential for targeting these enzymes in treatment of diarrheal disorders. Ion transport was measured as short-circuit current changes across voltage-clamped monolayers of T(84) cells and mouse colon. The antidiarrheal efficacy of dimethyloxallyl glycine (DMOG) was tested in a mouse model of allergic disease. Hydroxylase inhibition with DMOG attenuated Ca(2+)- and cAMP-dependent secretory responses in voltage-clamped T(84) cells to 20.2 ± 2.6 and 38.8 ± 6.7% (n=16; P≤0.001) of those in control cells, respectively. Antisecretory actions of DMOG were time and concentration dependent, being maximal after 18 h of DMOG (1 mM) treatment. DMOG specifically inhibited Na(+)\\/K(+)-ATPase pump activity without altering its expression or membrane localization. In mice, DMOG inhibited agonist-induced secretory responses ex vivo and prevented allergic diarrhea in vivo. In conclusion, hydroxylases are important regulators of epithelial Cl(-) and fluid secretion and present a promising target for development of new drugs to treat transport disorders.

  11. Experimental inhibition of porcupine-mediated Wnt O-acylation attenuates kidney fibrosis.

    Science.gov (United States)

    Madan, Babita; Patel, Mehul B; Zhang, Jiandong; Bunte, Ralph M; Rudemiller, Nathan P; Griffiths, Robert; Virshup, David M; Crowley, Steven D

    2016-05-01

    Activated Wnt signaling is critical in the pathogenesis of renal fibrosis, a final common pathway for most forms of chronic kidney disease. Therapeutic intervention by inhibition of individual Wnts or downstream Wnt/β-catenin signaling has been proposed, but these approaches do not interrupt the functions of all Wnts nor block non-canonical Wnt signaling pathways. Alternatively, an orally bioavailable small molecule, Wnt-C59, blocks the catalytic activity of the Wnt-acyl transferase porcupine, and thereby prevents secretion of all Wnt isoforms. We found that inhibiting porcupine dramatically attenuates kidney fibrosis in the murine unilateral ureteral obstruction model. Wnt-C59 treatment similarly blunts collagen mRNA expression in the obstructed kidney. Consistent with its actions to broadly arrest Wnt signaling, porcupine inhibition reduces expression of Wnt target genes and bolsters nuclear exclusion of β-catenin in the kidney following ureteral obstruction. Importantly, prevention of Wnt secretion by Wnt-C59 blunts expression of inflammatory cytokines in the obstructed kidney that otherwise provoke a positive feedback loop of Wnt expression in collagen-producing fibroblasts and epithelial cells. Thus, therapeutic targeting of porcupine abrogates kidney fibrosis not only by overcoming the redundancy of individual Wnt isoforms but also by preventing upstream cytokine-induced Wnt generation. These findings reveal a novel therapeutic maneuver to protect the kidney from fibrosis by interrupting a pathogenic crosstalk loop between locally generated inflammatory cytokines and the Wnt/β-catenin signaling pathway.

  12. MK801 attenuates secondary injury in a mouse experimental compression model of spinal cord trauma

    Directory of Open Access Journals (Sweden)

    Meli Rosaria

    2011-04-01

    Full Text Available Abstract Background Glutamergic excitotoxicity has been shown to play a deleterious role in the pathophysiology of spinal cord injury (SCI. The aim of this study was to investigate the neuroprotective effect of dizocilpine maleate, MK801 (2 mg/Kg, 30 min and 6 hours after injury in a mice model of SCI. The spinal cord trauma was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. Results Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration and apoptosis. In this study we clearly demonstrated that administration of MK801 attenuated all inflammatory parameters. In fact 24 hours after injury, the degree of spinal cord inflammation and tissue injury (evaluated as histological score, infiltration of neutrophils, NF-κB activation, iNOS, cytokines levels (TNF-α and IL-1β, neurotrophin expression were markedly reduced by MK801 treatment. Moreover, in a separate set of experiments, we have demonstrated that MK801 treatment significantly improved the recovery of locomotory function. Conclusions Blockade of NMDA by MK801 lends support to the potential importance of NMDA antagonists as therapeutic agents in the treatment of acute spinal cord injury.

  13. Carvacrol attenuates N-nitrosodiethylamine induced liver injury in experimental Wistar rats

    Directory of Open Access Journals (Sweden)

    Balan Rajan

    2015-06-01

    Full Text Available Carvacrol is a main constituent in the essential oils of countless aromatic plants including Origanum Vulgare and Thymus vulgari, which has been assessed for substantial pharmacological properties. In recent years, notable research has been embarked on to establish the biological actions of Carvacrol for its promising use in clinical applications. The present study is an attempt to reveal the protective role of Carvacrol against N-Nitrosodiethylamine (DEN induced hepatic injury in male Wistar albino rats. DEN is an egregious toxin, present in numerous environmental factors, which enhances chemical driven liver damage by inducing oxidative stress and cellular injury. Administration of DEN (200 mg/kg bodyweight, I.P to rats results in elevated marker enzymes (in both serum and tissue. Carvacrol (15 mg/kg body weight suppressed the elevation of marker enzymes (in both serum and tissue and augmented the antioxidants levels. The hoisted activities of Phase I enzymes and inferior activities of Phase II enzymes were observed in DEN-administered animals, whereas Carvacrol treated animals showed improved near normal activity. Histological observations also support the protective role of Carvacrol against DEN induced liver damage. Final outcome from our findings intimate that Carvacrol might be beneficial in attenuating toxin induced liver damage.

  14. Synchronous occurrence of collagenous colitis and pseudomembranous colitis.

    Science.gov (United States)

    Vesoulis, Z; Lozanski, G; Loiudice, T

    2000-04-01

    Synchronous collagenous and pseudomembranous colitis has not been previously reported. A 73-year-old woman presented with chronic watery diarrhea and abdominal cramping of six weeks' duration. Biopsies of the colon revealed findings of collagenous colitis involving the endoscopically normal right colon, and superimposed collagenous and pseudomembranous colitis involving the rectosigmoid colon. Endoscopically, the left colon revealed discrete ulcerative plaques, and Clostridium difficile toxin A assay was positive. The patient partially responded to a three-week regimen of metronidazole, and symptoms resolved completely with subsequent steroid therapy. At follow-up endoscopy four months later, colon biopsies demonstrated persistence of subepithelial collagen but no pseudomembranes. The patient remained asymptomatic during this interval. Collagenous colitis has been reported in association with other inflammatory bowel diseases, including lymphocytic colitis, sprue and idiopathic inflammatory bowel disease. This unique association of collagenous colitis with an endotoxigenic inflammatory bowel disease is presented with a review of related disease features.

  15. A novel benzenediamine derivate rescued mice from experimental sepsis by attenuating proinflammatory mediators via IRAK4.

    Science.gov (United States)

    Dou, Huan; Song, Yuxian; Liu, Xianqin; Yang, Liu; Jiang, Nan; Chen, Dai; Li, Erguang; Tan, Renxiang; Hou, Yayi

    2014-08-01

    We designed and synthesized a novel benzenediamine derivate, FC-99, that was tested for its ability to protect mice from experimental sepsis. Moreover, we sought to determine whether FC-99 could control a bacterial infection and to clarify the mechanism by which FC-99 inhibited LPS-activated macrophages. The effects of FC-99 on inflammation were evaluated in two experimental sepsis models and in cultured macrophages. Microarrays and docking and molecular dynamics simulations were used to determine the target of FC-99. Surface plasmon resonance and molecular detection were performed to confirm the direct interaction of FC-99 with its target. FC-99 protected mice from experimental sepsis. The mice that received FC-99 exhibited a diminished inflammatory response, had a lower local bacterial burden, and experienced a significantly improved survival rate. Genome-wide transcriptional profiling of FC-99-treated macrophages identified IRAK4 as a drug-regulated gene involved in LPS/TLR4 signaling. A computer search and calculations indicated that IRAK4 directly interacted with FC-99. Surface plasmon resonance, IRAK4-regulated signaling pathway analysis, and gene expression profiling of proinflammatory mediators confirmed the direct interaction between FC-99 and IRAK4. FC-99 is a potential therapeutic molecule for sepsis that alleviated experimental sepsis by directly inhibiting IRAK4 activation, which represents a novel target for sepsis therapy.

  16. Tropisetron suppresses colitis-associated cancer in a mouse model in the remission stage.

    Science.gov (United States)

    Amini-Khoei, Hossein; Momeny, Majid; Abdollahi, Alireza; Dehpour, Ahmad Reza; Amiri, Shayan; Haj-Mirzaian, Arya; Tavangar, Seyed Mohammad; Ghaffari, Seyed Hamid; Rahimian, Reza; Mehr, Shahram Ejtemaei

    2016-07-01

    Patients with inflammatory bowel disease (IBD) have a high risk for development of colitis-associated cancer (CAC). Serotonin is a neurotransmitter produced by enterochromaffin cells of the intestine. Serotonin and its receptors, mainly 5-HT3 receptor, are overexpressed in IBD and promote development of CAC through production of inflammatory cytokines. In the present study, we demonstrated the in vivo activity of tropisetron, a 5-HT3 receptor antagonist, against experimental CAC. CAC was induced by azoxymethane (AOM)/dextran sodium sulfate (DDS) in BALB/c mice. The histopathology of colon tissue was performed. Beta-catenin and Cox-2 expression was evaluated by immunohistochemistry as well as quantitative reverse transcription-PCR (qRT-PCR). Alterations in the expression of 5-HT3 receptor and inflammatory-associated genes such as Il-1β, Tnf-α, Tlr4 and Myd88 were determined by qRT-PCR. Our results showed that tumor development in tropisetron-treated CAC group was significantly lower than the controls. The qRT-PCR analysis demonstrated that the expression of 5-HT3 receptor was significantly increased following CAC induction. In addition, tropisetron reduced expression of β-catenin and Cox-2 in the CAC experimental group. The levels of Il-1β, Tnf-α, Tlr4 and Myd88 were significantly decreased upon tropisetron treatment in the AOM/DSS group. Taken together, our data show that tropisetron inhibits development of CAC probably by attenuation of inflammatory reactions in the colitis.

  17. Keratinocyte growth factor gene therapy ameliorates ulcerative colitis in rats

    Institute of Scientific and Technical Information of China (English)

    Chun-Jie Liu; Ji-De Jin; Tong-De Lv; Zu-Ze Wu; Xiao-Qin Ha

    2011-01-01

    AIM: To investigate the effect of keratinocyte growth factor (KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model. METHODS: The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5% (v/v) acetic acid. Twenty-four hours after exposed to acetic acid, rats were divided into three experimental groups: control group, attenuated Salmonella typhimurium Ty21a strain (SP) group and SP strain carrying human KGF gene (SPK) group, and they were separately administered orally with 10% NaHCO3, SP or SPK. Animals were sacrificed and colonic tissues were harvested respectively on day 3, 5, 7 and 10 after administration. Weights of rats, colonic weight/ length ratio and stool score were evaluated. Histological changes of colonic tissues were examined by hematoxylin and eosin (HE) staining method. The expression of KGF, KGF receptor (KGFR) and TNF-α were measured either by enzyme-linked immunosorbent assay or Western blotting. Immunohistochemistry was used to detect the cellular localization of KGFR and Ki67. In addition, superoxide dismutase (SOD) activity and malondialdehyde (MDA) contents in the homogenate were measured. RESULTS: Body weight and colonic weight/length ratio were declined in SPK group compared with SP and control groups (body weight: 272.78 ± 17.92 g vs 243.72 ± 14.02 g and 240.68 ± 12.63 g, P < 0.01; colonic weight/length ratio: 115.76 ± 7.47 vs 150.32 ± 5.99 and 153.67 ± 5.50 mg/cm, P < 0.01). Moreover, pathological changes of damaged colon were improved in SPK group as well. After administration of SPK strain, KGF expression increased markedly from the 3rd d, and remained at a high level till the 10th d. Furthermore, KGFR expression and Ki67 expression elevated, whereas TNF-α expression was inhibited in SPK group. In the group administered with SPK, SOD activity increased significantly (d 5: 26.18 ± 5.84 vs 18.12 ± 3.30 and 18.79 ± 4.74 U/mg, P < 0.01; d 7: 35.48 ± 3.35 vs 22.57 ± 3.44 and 21.69 ± 3.94 U

  18. Akt1-mediated fast/glycolytic skeletal muscle growth attenuates renal damage in experimental kidney disease.

    Science.gov (United States)

    Hanatani, Shinsuke; Izumiya, Yasuhiro; Araki, Satoshi; Rokutanda, Taku; Kimura, Yuichi; Walsh, Kenneth; Ogawa, Hisao

    2014-12-01

    Muscle wasting is frequently observed in patients with kidney disease, and low muscle strength is associated with poor outcomes in these patients. However, little is known about the effects of skeletal muscle growth per se on kidney diseases. In this study, we utilized a skeletal muscle-specific, inducible Akt1 transgenic (Akt1 TG) mouse model that promotes the growth of functional skeletal muscle independent of exercise to investigate the effects of muscle growth on kidney diseases. Seven days after Akt1 activation in skeletal muscle, renal injury was induced by unilateral ureteral obstruction (UUO) in Akt1 TG and wild-type (WT) control mice. The expression of atrogin-1, an atrophy-inducing gene in skeletal muscle, was upregulated 7 days after UUO in WT mice but not in Akt1 TG mice. UUO-induced renal interstitial fibrosis, tubular injury, apoptosis, and increased expression of inflammatory, fibrosis-related, and adhesion molecule genes were significantly diminished in Akt1 TG mice compared with WT mice. An increase in the activating phosphorylation of eNOS in the kidney accompanied the attenuation of renal damage by myogenic Akt1 activation. Treatment with the NOS inhibitor L-NAME abolished the protective effect of skeletal muscle Akt activation on obstructive kidney disease. In conclusion, Akt1-mediated muscle growth reduces renal damage in a model of obstructive kidney disease. This improvement appears to be mediated by an increase in eNOS signaling in the kidney. Our data support the concept that loss of muscle mass during kidney disease can contribute to renal failure, and maintaining muscle mass may improve clinical outcome.

  19. Salvianolic acid B attenuates apoptosis and inflammation via SIRT1 activation in experimental stroke rats.

    Science.gov (United States)

    Lv, Hongdi; Wang, Ling; Shen, Jinchang; Hao, Shaojun; Ming, Aimin; Wang, Xidong; Su, Feng; Zhang, Zhengchen

    2015-06-01

    Silent information regulator 1 (SIRT1), a histone deacetylase, has been suggested to be effective in ischemic brain diseases. Salvianolic acid B (SalB) is a polyphenolic and one of the active components of Salvia miltiorrhiza Bunge. Previous studies suggested that SalB is protective against ischemic stroke. However, the role of SIRT1 in the protective effect of SalB against cerebral ischemia has not been explored. In this study, the rat brain was subjected to middle cerebral artery occlusion (MCAO). Before this surgery, rats were intraperitoneally administrated SalB with or without EX527, a specific SIRT1 inhibitor. The infarct volume, neurological score and brain water content were assessed. In addition, levels of TNF-α and IL-1β in the brain tissues were detected by commercial ELISA kits. And the expression levels of SIRT, Ac-FOXO1, Bcl-2 and Bax were detected by Western blot. The results suggested that SalB exerted a cerebral-protective effect, as shown by reduced infarct volume, lowered brain edema and increased neurological scores. SalB also exerted anti-inflammatory effects as indicated by the decreased TNF-α and IL-1β levels in the brain tissue. Moreover, SalB upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of Ac-FOXO1 and Bax. These effects of SalB were abolished by EX527 treatment. In summary, our results demonstrate that SalB treatment attenuates brain injury induced by ischemic stoke via reducing apoptosis and inflammation through the activation of SIRT1 signaling.

  20. Propylthiouracil Attenuates Experimental Pulmonary Hypertension via Suppression of Pen-2, a Key Component of Gamma-Secretase.

    Science.gov (United States)

    Lai, Ying-Ju; Chang, Gwo-Jyh; Yeh, Yung-Hsin; Pang, Jong-Hwei S; Huang, Chung-Chi; Chen, Wei-Jan

    2015-01-01

    Gamma-secretase-mediated Notch3 signaling is involved in smooth muscle cell (SMC) hyper-activity and proliferation leading to pulmonary arterial hypertension (PAH). In addition, Propylthiouracil (PTU), beyond its anti-thyroid action, has suppressive effects on atherosclerosis and PAH. Here, we investigated the possible involvement of gamma-secretase-mediated Notch3 signaling in PTU-inhibited PAH. In rats with monocrotaline-induced PAH, PTU therapy improved pulmonary arterial hypertrophy and hemodynamics. In vitro, treatment of PASMCs from monocrotaline-treated rats with PTU inhibited their proliferation and migration. Immunocyto, histochemistry, and western blot showed that PTU treatment attenuated the activation of Notch3 signaling in PASMCs from monocrotaline-treated rats, which was mediated via inhibition of gamma-secretase expression especially its presenilin enhancer 2 (Pen-2) subunit. Furthermore, over-expression of Pen-2 in PASMCs from control rats increased the capacity of migration, whereas knockdown of Pen-2 with its respective siRNA in PASMCs from monocrotaline-treated rats had an opposite effect. Transfection of PASMCs from monocrotaline-treated rats with Pen-2 siRNA blocked the inhibitory effect of PTU on PASMC proliferation and migration, reflecting the crucial role of Pen-2 in PTU effect. We present a novel cell-signaling paradigm in which overexpression of Pen-2 is essential for experimental pulmonary arterial hypertension to promote motility and growth of smooth muscle cells. Propylthiouracil attenuates experimental PAH via suppression of the gamma-secretase-mediated Notch3 signaling especially its presenilin enhancer 2 (Pen-2) subunit. These findings provide a deep insight into the pathogenesis of PAH and a novel therapeutic strategy.

  1. Propylthiouracil Attenuates Experimental Pulmonary Hypertension via Suppression of Pen-2, a Key Component of Gamma-Secretase.

    Directory of Open Access Journals (Sweden)

    Ying-Ju Lai

    Full Text Available Gamma-secretase-mediated Notch3 signaling is involved in smooth muscle cell (SMC hyper-activity and proliferation leading to pulmonary arterial hypertension (PAH. In addition, Propylthiouracil (PTU, beyond its anti-thyroid action, has suppressive effects on atherosclerosis and PAH. Here, we investigated the possible involvement of gamma-secretase-mediated Notch3 signaling in PTU-inhibited PAH. In rats with monocrotaline-induced PAH, PTU therapy improved pulmonary arterial hypertrophy and hemodynamics. In vitro, treatment of PASMCs from monocrotaline-treated rats with PTU inhibited their proliferation and migration. Immunocyto, histochemistry, and western blot showed that PTU treatment attenuated the activation of Notch3 signaling in PASMCs from monocrotaline-treated rats, which was mediated via inhibition of gamma-secretase expression especially its presenilin enhancer 2 (Pen-2 subunit. Furthermore, over-expression of Pen-2 in PASMCs from control rats increased the capacity of migration, whereas knockdown of Pen-2 with its respective siRNA in PASMCs from monocrotaline-treated rats had an opposite effect. Transfection of PASMCs from monocrotaline-treated rats with Pen-2 siRNA blocked the inhibitory effect of PTU on PASMC proliferation and migration, reflecting the crucial role of Pen-2 in PTU effect. We present a novel cell-signaling paradigm in which overexpression of Pen-2 is essential for experimental pulmonary arterial hypertension to promote motility and growth of smooth muscle cells. Propylthiouracil attenuates experimental PAH via suppression of the gamma-secretase-mediated Notch3 signaling especially its presenilin enhancer 2 (Pen-2 subunit. These findings provide a deep insight into the pathogenesis of PAH and a novel therapeutic strategy.

  2. Involvement of MAPK/NF-κB signaling in the activation of the cholinergic anti-inflammatory pathway in experimental colitis by chronic vagus nerve stimulation.

    Directory of Open Access Journals (Sweden)

    Peng Sun

    Full Text Available BACKGROUND: Autonomic nervous system dysfunction is implicated in the etiopathogenesis of inflammatory bowel diseases (IBD. Therapies that increase cardiovagal activity, such as Mind-Body interventions, are currently confirmed to be effective in clinical trials in IBD. However, a poor understanding of pathophysiological mechanisms limits the popularization of therapies in clinical practice. The aim of the present study was to explore the mechanisms of these therapies against 2,4,6-trinitrobenzenesulfonic acid (TNBS-induced colitis in rats using a chronic vagus nerve stimulation model in vivo, as well as the lipopolysaccharide (LPS-induced inflammatory response in human epithelial colorectal adenocarcinoma cells (Caco-2 by acetylcholine in vitro. METHODS AND RESULTS: Colitis was induced in rats with rectal instillation of TNBS, and the effect of chronic VNS (0.25 mA, 20 Hz, 500 ms on colonic inflammation was evaluated. Inflammatory responses were assessed by disease activity index (DAI, histological scores, myeloperoxidase (MPO activity, inducible nitric oxide synthase (iNOS, TNF-α and IL-6 production. The expression of Mitogen-activated protein kinases (MAPK family members, IκB-α, and nuclear NF-κB p65 were studied by immunoblotting. Heart rate variability (HRV analysis was also applied to assess the sympathetic-vagal balance. DAI, histological scores, MPO activity, iNOS, TNF-α and IL-6 levels were significantly decreased by chronic VNS. Moreover, both VNS and acetylcholine reduced the phosphorylation of MAPKs and prevented the nuclear translocation of NF-κB p65. Methyllycaconitine (MLA only reversed the inhibitory effect on p-ERK and intranuclear NF-κB p65 expression by ACh in vitro, no significant change was observed in the expression of p-p38 MAPK or p-JNK by MLA. CONCLUSION: Vagal activity modification contributes to the beneficial effects of the cholinergic anti-inflammatory pathway in IBD-related inflamed colonic mucosa based on the

  3. Study on Combining Lactobacilli Strain with Clostridium Butyricum Strain on Mice Experimental Ulcerative Colitis%乳酸杆菌联合丁酸梭菌治疗小鼠溃疡性结肠炎的研究

    Institute of Scientific and Technical Information of China (English)

    左和宁; 杨伟峰

    2009-01-01

    Objective Aim To investigate the therapeutic effect of combination of lactobacilli strain with clostridium butyricum strain on experimental ulcerative colitis.Methods To observed the effects of lactobacilli strain with clostridium butyricum strain,the mice ulcerative colitis was induced by Dextran sulfate Sodium(DSS) and tissue biochemical indexes and the expression of EMAP-Ⅱ in the colonic mucosa were detected.Results Lactobacilli strain and clostridium butyricum strain significantly abbreviated the damage of colonic tissue and suppressed the expression of EMAP-Ⅱ.moreover,there were the lightest histological damage and the lowest expression of EMAP-Ⅱ in lactobacilli strain combined with clostridium butyricum strain.Conclusion Both lactobacilli strain and clostridium butyricum strain show therapeutic effect on DSS induced mice ulcerative colitis.The coeffects on ulcerative colitis were observed in combination of lactobacilli strain with clostridium butyricum strain.There are lower expression of EMAP-Ⅱ in the combination group than that in the two strain group alone,which may be the molecule mechanism of the effect on mice UC partly.%目的 观察联用乳酸杆菌和丁酸梭菌对小鼠急性溃疡性结肠炎的疗效并探讨其治疗机制.方法 70只小鼠随机分为7组,正常对照组:正常饮食,无特殊处理;模型组:饮用DSS造模;阴性对照组:仅用无菌0.9%氯化钠溶液灌胃;阳性对照组:用巴柳氮(40mg/ml)灌胃;乳酸杆菌组:DSS造模+2×1010/ml 乳酸杆菌菌液灌胃;丁酸梭菌组:DSS造模+2×108/ml 丁酸梭菌菌液灌胃;合用组:DSS造模+(2×1010/ml 乳酸杆菌菌液+2×108/ml 丁酸梭菌菌液灌胃.建立DSS诱导的小鼠急性溃疡性结肠炎模型,观察给予乳酸杆菌和丁酸梭菌治疗后,小鼠结肠黏膜的病理改变和EMAP-Ⅱ表达的变化.结果 乳酸杆菌和丁酸梭菌可明显减轻小鼠结肠黏膜的损伤;可明显抑制EMAP-Ⅱ的表达,尤以两菌合用组

  4. DSS与TNBS诱导大鼠实验性结肠炎模型的对比研究%Experimental Colitis Model Induced by DSS and TNBS in Rats:A Comparative Study

    Institute of Scientific and Technical Information of China (English)

    赵平; 董蕾; 罗金燕; 管海涛; 宋亚华; 龚均

    2015-01-01

    Background:As the empirical studies on human body are restricted extremely,the establishment and selection of suitable animal models are important for researches on ulcerative colitis( UC ). Aims:To compare the symptoms and colonic pathology of rat models with experimental colitis induced by dextran sulfate sodium( DSS ) and trinitrobenzene sulfonic acid( TNBS),so as to provide a reference for selecting animal models in UC-related studies. Methods:Drinking 4% DSS freely for 7 days or intrarectal administration of single dose 100 mg/kg TNBS-50% ethanol were used to establish experimental colitis model in Sprague-Dawley rats. The disease activity index( DAI)was assessed dynamically during the course of experiment. The whole colon was removed in batches for measurements of colonic damage score and activity of myeloperoxidase(MPO)at different time points. Results:The DAI score reached the peak at the 7th day and the 2nd day in DSS group and TNBS group,respectively,and decreased gradually afterwards. Six and one deaths occurred during the experimental course in DSS and TNBS groups,respectively. In DSS group,the duration of inflammation was short,the colonic injury was moderate and recovered after drug withdrawal. At the 18th day,the colonic damage score and MPO activity was 0. 25 ± 0. 50 and(0. 80 ± 0. 33)U/g,respectively,and no significant differences were seen between DSS group and normal control group. In TNBS group,the duration of inflammation was longer and the colonic injury was more severe. At the 21st day,the colonic damage score and MPO activity was 3. 60 ± 0. 55 and( 1. 60 ± 0. 39 ) U/g, respectively,and chronic inflammation was observed histologically. Conclusions:Both DSS and TNBS can induce experimental colitis model in rats. The course of TNBS-induced colitis model presents a transformation of acute to chronic inflammation,and may be more suitable for treatment-related studies of UC.%背景:鉴于人体实验受到诸多限制,建立、选择合

  5. Carnosic acid attenuates renal injury in an experimental model of rat cisplatin-induced nephrotoxicity.

    Science.gov (United States)

    Sahu, Bidya Dhar; Rentam, Kiran Kumar Reddy; Putcha, Uday Kumar; Kuncha, Madhusudana; Vegi, Ganga Modi Naidu; Sistla, Ramakrishna

    2011-12-01

    Nephrotoxicity is one of the serious dose limiting side effects of cisplatin when used in the treatment of various malignant conditions. Accumulating evidence suggests that oxidative stress caused by free radicals and apoptosis of renal cells contributes to the pathogenesis of cisplatin-induced nephrotoxicity. Present study was aimed to explore the effect of carnosic acid, a potent antioxidant, against cisplatin induced oxidative stress and nephrotoxicity in rats. A single dose of cisplatin (7.5mg/kg) caused marked renal damage, characterized by a significant (PGSH (reduced glutathione) levels and lowered tissue nitrite, SOD (superoxide dismutase), CAT (catalase), GSH-Px (glutathione peroxidase), GR (glutathione reductase) and GST (glutathione S-transferase) levels compared to normal control. Carnosic acid treatment significantly (PGSH-Px, GR and GST compared to cisplatin control. The present study demonstrates that carnosic acid has a protective effect on cisplatin induced experimental nephrotoxicity and is attributed to its potent antioxidant and antiapoptotic properties.

  6. Ulcerative Colitis in Infancy

    OpenAIRE

    Md Rukunuzzaman; A. S. M. Bazlul Karim

    2011-01-01

    Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder of colon. Frequency of UC is gradually increasing over few years worldwide. Prevalence is 35 to 100/100 000 people in USA, 1% of them are infants. UC develops in a genetically predisposed individual with altered intestinal immune response. An eight-month-old girl presented with loose bloody stool, growth failure, and moderate pallor. The girl was diagnosed as a case of UC by colonoscopy and biopsy. Treatment was thereafter ...

  7. A novel urotensin II receptor antagonist, KR-36996, improved cardiac function and attenuated cardiac hypertrophy in experimental heart failure.

    Science.gov (United States)

    Oh, Kwang-Seok; Lee, Jeong Hyun; Yi, Kyu Yang; Lim, Chae Jo; Park, Byung Kil; Seo, Ho Won; Lee, Byung Ho

    2017-03-15

    Urotensin II and its receptor are thought to be involved in various cardiovascular diseases such as heart failure, pulmonary hypertension and atherosclerosis. Since the regulation of the urotensin II/urotensin II receptor offers a great potential for therapeutic strategies related to the treatment of cardiovascular diseases, the study of selective and potent antagonists for urotensin II receptor is more fascinating. This study was designed to determine the potential therapeutic effects of a newly developed novel urotensin II receptor antagonist, N-(1-(3-bromo-4-(piperidin-4-yloxy)benzyl)piperidin-4-yl)benzo[b]thiophene-3-carboxamide (KR-36996), in experimental models of heart failure. KR-36996 displayed a high binding affinity (Ki=4.44±0.67nM) and selectivity for urotensin II receptor. In cell-based study, KR-36996 significantly inhibited urotensin II-induced stress fiber formation and cellular hypertrophy in H9c2UT cells. In transverse aortic constriction-induced cardiac hypertrophy model in mice, the daily oral administration of KR-36996 (30mg/kg) for 14 days significantly decreased left ventricular weight by 40% (Preceptor antagonist could efficiently attenuate both cardiac hypertrophy and dysfunction in experimental heart failure. KR-36996 may be useful as an effective urotensin II receptor antagonist for pharmaceutical or clinical applications.

  8. Caffeic acid attenuates oxidative stress, learning and memory deficit in intra-cerebroventricular streptozotocin induced experimental dementia in rats.

    Science.gov (United States)

    Deshmukh, Rahul; Kaundal, Madhu; Bansal, Vikas; Samardeep

    2016-07-01

    Oxidative stress has been implicated in cognitive decline as seen during normal aging and in sporadic Alzheimer's disease (AD). Caffeic acid, a polyphenolic compound, has been reported to possess potent antioxidant and neuroprotective properties. The role of caffeic acid in experimental dementia is not fully understood. Thus the present study was designed to investigate the therapeutic potential of caffeic acid in streptozotocin (STZ)-induced experimental dementia of Alzheimer's type in rats. Streptozotocin (STZ) was administered intracerebroventrically (ICV) on day 1 and 3 (3mg/kg, ICV bilaterally) in Wistar rats. Caffeic acid was administered (10, 20 and 40mg/kg/day p.o.) 1h following STZ infusion upto 21st day. Morris water maze and object recognition task were used to assess learning and memory in rats. Terminally, acetylcholinesterase (AChE) activity and the levels of oxido-nitrosative stress markers were determined in cortical and hippocampal brain regions of rats. STZ produced significant (plearning and memory impairment, oxido-nitrosative stress and cholinergic deficit in rats. Whereas, caffeic acid treatment significantly (p<0.001) and dose dependently attenuated STZ induced behavioral and biochemical abnormalities in rats. The observed cognitive improvement following caffeic acid in STZ treated rats may be due to its antioxidant activity and restoration of cholinergic functions. Our results suggest the therapeutic potential of caffeic acid in cognitive disorders such as AD.

  9. Anti-malarial drug artesunate attenuates experimental allergic asthma via inhibition of the phosphoinositide 3-kinase/Akt pathway.

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    Chang Cheng

    Full Text Available BACKGROUND: Phosphoinositide 3-kinase (PI3K/Akt pathway is linked to the development of asthma. Anti-malarial drug artesunate is a semi-synthetic derivative of artemisinin, the principal active component of a medicinal plant Artemisia annua, and has been shown to inhibit PI3K/Akt activity. We hypothesized that artesunate may attenuate allergic asthma via inhibition of the PI3K/Akt signaling pathway. METHODOLOGY/PRINCIPAL FINDINGS: Female BALB/c mice sensitized and challenged with ovalbumin (OVA developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Artesunate dose-dependently inhibited OVA-induced increases in total and eosinophil counts, IL-4, IL-5, IL-13 and eotaxin levels in bronchoalveolar lavage fluid. It attenuated OVA-induced lung tissue eosinophilia and airway mucus production, mRNA expression of E-selectin, IL-17, IL-33 and Muc5ac in lung tissues, and airway hyperresponsiveness to methacholine. In normal human bronchial epithelial cells, artesunate blocked epidermal growth factor-induced phosphorylation of Akt and its downstream substrates tuberin, p70S6 kinase and 4E-binding protein 1, and transactivation of NF-κB. Similarly, artesunate blocked the phosphorylation of Akt and its downstream substrates in lung tissues from OVA-challenged mice. Anti-inflammatory effect of artesunate was further confirmed in a house dust mite mouse asthma model. CONCLUSION/SIGNIFICANCE: Artesunate ameliorates experimental allergic airway inflammation probably via negative regulation of PI3K/Akt pathway and the downstream NF-κB activity. These findings provide a novel therapeutic value for artesunate in the treatment of allergic asthma.

  10. Lactobacillus rhamnosus GG and Bifidobacterium longum attenuate lung injury and inflammatory response in experimental sepsis.

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    Ludmila Khailova

    Full Text Available INTRODUCTION: Probiotic use to prevent nosocomial gastrointestinal and potentially respiratory tract infections in critical care has shown great promise in recent clinical trials of adult and pediatric patients. Despite well-documented benefits of probiotic use in intestinal disorders, the potential for probiotic treatment to reduce lung injury following infection and shock has not been well explored. OBJECTIVE: Evaluate if Lactobacillus rhamnosus GG (LGG or Bifidobacterium longum (BL treatment in a weanling mouse model of cecal ligation and puncture (CLP peritonitis will protect against lung injury. METHODS: 3 week-old FVB/N mice were orally gavaged with 200 µl of either LGG, BL or sterile water (vehicle immediately prior to CLP. Mice were euthanized at 24 h. Lung injury was evaluated via histology and lung neutrophil infiltration was evaluated by myeloperoxidase (MPO staining. mRNA levels of IL-6, TNF-α, MyD88, TLR-4, TLR-2, NFΚB (p50/p105 and Cox-2 in the lung analyzed via real-time PCR. TNF-α and IL-6 in lung was analyzed via ELISA. RESULTS: LGG and BL treatment significantly improved lung injury following experimental infection and sepsis and lung neutrophil infiltration was significantly lower than in untreated septic mice. Lung mRNA and protein levels of IL-6 and TNF-α and gene expression of Cox-2 were also significantly reduced in mice receiving LGG or BL treatment. Gene expression of TLR-2, MyD88 and NFΚB (p50/p105 was significantly increased in septic mice compared to shams and decreased in the lung of mice receiving LGG or BL while TLR-4 levels remained unchanged. CONCLUSIONS: Treatment with LGG and BL can reduce lung injury following experimental infection and sepsis and is associated with reduced lung inflammatory cell infiltrate and decreased markers of lung inflammatory response. Probiotic therapy may be a promising intervention to improve clinical lung injury following systemic infection and sepsis.

  11. Effect of folate deficiency on experimental colitis in mice induced by dextran sodium sulfate%叶酸缺乏对葡聚糖硫酸钠诱导的小鼠实验性结肠炎的影响

    Institute of Scientific and Technical Information of China (English)

    马玉萍; 肖锐; 方维丽; 李海东; 刘文天

    2015-01-01

    Objective To investigate whether folate deficiency cause high expression level of interferon gamma (IFN-γ) resulted from IFN-γ gene ( IFNG) hypomethylation and then promote the pathogenesis and development of ulcerative colitis (UC ) in a dextran sulfate sodium (DSS )-induced experimental colitis model in mice .Methods A total of 24 female BALB/c mice were divided into four groups ,six mice in each group , including folate deficient/DSS+ group , standard diet/DSS+ group , standard diet/DSS - group and folate deficient/DSS- group .At the beginning of the sixth week since fed , the mice of model groups were treated with 5% DSS to establish experimental colitis .By the end of the sixth week ,disease activity index (DAI) of colitis and histological changes were evaluated .The folate level of peripheral blood serum of mice were detected by enzyme-linked immunosorbent assay (ELISA ) . The expression of IFN-γ in colonic mucosa of mice was examined by immunohistochemistry . The methylation level of CpG island in the promoter region of IFNG was determined by methylation specific polymerase chain reaction (MSP) .The t test was used for measurement data .Chi square test was performed for comparison between groups of count data . Spearman correlation analysis was used for correlation analysis .Results The folate levels of peripheral blood serum of folate deficiency/DSS+ group and folate deficiency/DSS- group ((2 .70 ± 0 .19) and (2 .80 ± 0 .25)μg/L) were significantly lower than those of standard diet/DSS+ group and standard diet/DSS- group ((13 .62 ± 0 .38 ) and (13 .52 ± 0 .77)μg/L ,t= -63 .33、32 .27 ,both P< 0 .05) ,resepectively .The expression of IFN-γ in colonic mucosa of folate deficiency/DSS+ group and standard diet/DSS+ group were significantly higher than those of folate deficiency/DSS- group and standard diet/DSS- group (χ2 = 22 .18 ,P< 0 .05 ) . And the expression of IFN-γ in colonic mucosa of folate deficiency/DSS+ group was also higher than that of

  12. Apigenin Attenuates Experimental Autoimmune Myocarditis by Modulating Th1/Th2 Cytokine Balance in Mice.

    Science.gov (United States)

    Zhang, Shouxin; Liu, Xiaoyan; Sun, Chengming; Yang, Jun; Wang, Lihong; Liu, Jie; Gong, Lei; Jing, Yanyan

    2016-04-01

    This study aims to investigate the protective effect of apigenin on the development of experimental autoimmune myocarditis (EAM) and the underlying mechanisms. An EAM model was induced in BALB/c mice by the injection of porcine cardiac myosin. Apigenin was orally administered from day 1 to 21. The severity of myocarditis was assessed by determination of heart weight/body weight ratio (HW/BW) and histopathological evaluation. Echocardiography was conducted to evaluate the cardiac function and heart structure. Antigen-specific T cell proliferation responses to cardiac myosin were evaluated by the lymphocyte proliferation assay. ELISA was used to determine serum levels of type 1 helper (Th1) and Th2 cytokines. Apigenin treatment significantly decreased HW/BW. Histopathologic analysis showed that the infiltration of inflammatory cells was reduced significantly by apigenin treatment. Meanwhile, apigenin administration effectively ameliorated autoimmune myocarditis-induced cardiac hypertrophy and cardiac dysfunction as well as inhibited lymphocyte proliferation in mice immunized with myosin. Furthermore, Th1 cytokines tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-2 (IL-2) were significantly downregulated, while Th2 cytokines IL-4 and IL-10 were markedly upregulated. The results indicated that apigenin can alleviate EAM due to its immunomodulatory reactions in modification of helper T cell balance.

  13. Ceruloplasmin gene-deficient mice with experimental autoimmune encephalomyelitis show attenuated early disease evolution.

    Science.gov (United States)

    Gresle, Melissa M; Schulz, Katrin; Jonas, Anna; Perreau, Victoria M; Cipriani, Tania; Baxter, Alan G; Miranda-Hernandez, Socorro; Field, Judith; Jokubaitis, Vilija G; Cherny, Robert; Volitakis, Irene; David, Samuel; Kilpatrick, Trevor J; Butzkueven, Helmut

    2014-06-01

    We conducted a microarray study to identify genes that are differentially regulated in the spinal cords of mice with the inflammatory disease experimental autoimmune encephalomyelitis (EAE) relative to healthy mice. In total 181 genes with at least a two-fold increase in expression were identified, and most of these genes were associated with immune function. Unexpectedly, ceruloplasmin (Cp), a ferroxidase that converts toxic ferrous iron to its nontoxic ferric form and also promotes the efflux of iron from astrocytes in the CNS, was shown to be highly upregulated (13.2-fold increase) in EAE spinal cord. Expression of Cp protein is known to be increased in several neurological conditions, but the role of Cp regulation in CNS autoimmune disease is not known. To investigate this, we induced EAE in Cp gene knockout, heterozygous, and wild-type mice. Cp knockout mice were found to have slower disease evolution than wild-type mice (EAE days 13-17; P = 0.05). Interestingly, Cp knockout mice also exhibited a significant increase in the number of astrocytes with reactive morphology in early EAE compared with wild-type mice at the same stage of disease. CNS iron levels were not increased with EAE in these mice. Based on these observations, we propose that an increase in Cp expression could contribute to tissue damage in early EAE. In addition, endogenous CP either directly or indirectly inhibits astrocyte reactivity during early disease, which could also worsen early disease evolution.

  14. Salvianolic Acid B Attenuates Experimental Pulmonary Fibrosis through Inhibition of the TGF-β Signaling Pathway.

    Science.gov (United States)

    Liu, Qingmei; Chu, Haiyan; Ma, Yanyun; Wu, Ting; Qian, Feng; Ren, Xian; Tu, Wenzhen; Zhou, Xiaodong; Jin, Li; Wu, Wenyu; Wang, Jiucun

    2016-06-09

    Pulmonary fibrosis is a progressive and fatal disorder. In our previous study, we found that the Yiqihuoxue formula (YQHX), a prescription of Traditional Chinese Medicine, had a curative effect on scleroderma, a typical fibrotic disease. The aim of this study was to determine the key ingredient mediating the therapeutic effects of YQHX and to examine its effect on pulmonary fibrosis, including its mechanism. Luciferase reporter assays showed that the most important anti-fibrotic component of the YQHX was Salviae miltiorrhiza (SM). Experiments performed using a bleomycin-instilled mouse model of pulmonary fibrosis showed that Salvianolic acid B (SAB), the major ingredient of SM, had strong anti-inflammatory and anti-fibrotic effects through its inhibition of inflammatory cell infiltration, alveolar structure disruption, and collagen deposition. Furthermore, SAB suppressed TGF-β-induced myofibroblastic differentiation of MRC-5 fibroblasts and TGF-β-mediated epithelial-to-mesenchymal transition of A549 cells by inhibiting both Smad-dependent signaling and the Smad-independent MAPK pathway. Taken together, our results suggest that SM is the key anti-fibrotic component of the YQHX and that SAB, the major ingredient of SM, alleviates experimental pulmonary fibrosis both in vivo and in vitro by inhibiting the TGF-β signaling pathway. Together, these results suggest that SAB potently inhibits pulmonary fibrosis.

  15. Evolution of Collagenous Colitis into Severe and Extensive Ulcerative Colitis

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    Hugh J Freeman

    2007-01-01

    Full Text Available Collagenous colitis is an inflammatory mucosal disorder of the colon with distinctive histopathological features, including a thickened subepithelial collagen layer. The clinical course is usually benign, but serious complications, including death, may occur. In the present report, a 69-year-old woman with watery diarrhea and collagenous colitis developed bloody diarrhea that was refractory to treatment medications, including corticosteroids and azathioprine. Endoscopic and histopathological studies showed a focal neutrophilic inflammatory process that progressed to a diffuse and extensive form of colitis, eventually requiring total proctocolectomy. Careful histological review of the resected colon showed no evidence of persistent collagenous colitis. These findings suggest an important need for continued long-term follow-up of patients with collagenous colitis because superimposed and serious colonic complications may occur, including a severe and extensive pancolitis refractory to medications and necessitating total proctocolectomy.

  16. Segmental Colitis Complicating Diverticular Disease

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    Guido Ma Van Rosendaal

    1996-01-01

    Full Text Available Two cases of idiopathic colitis affecting the sigmoid colon in elderly patients with underlying diverticulosis are presented. Segmental resection has permitted close review of the histopathology in this syndrome which demonstrates considerable similarity to changes seen in idiopathic ulcerative colitis. The reported experience with this syndrome and its clinical features are reviewed.

  17. Computed tomography of Crohn`s disease and ulcerative colitis; Computertomographische Morphologie von Morbus Crohn und Colitis ulcerosa

    Energy Technology Data Exchange (ETDEWEB)

    Klein, H.M. [Klinik fuer Radiologische Diagnostik der RWTH, Aachen (Germany); Wein, B. [Klinik fuer Radiologische Diagnostik der RWTH, Aachen (Germany); Adam, G. [Klinik fuer Radiologische Diagnostik der RWTH, Aachen (Germany); Ruppert, D. [Klinik fuer Radiologische Diagnostik der RWTH, Aachen (Germany); Guenther, R.W. [Klinik fuer Radiologische Diagnostik der RWTH, Aachen (Germany)

    1995-07-01

    We analysed the CT examinations of 109 patients with 197 involved bowel locations. 81 patients suffered from Crohn`s disease, 28 from ulcerative colitis. Diagnosis was based on the combination of clinical, endoscopic and histopathologic findings. Three radiologists evaluated the CT series concerning the presence of morphologic changes analogous to conventional radiographic findings. In Crohn`s disease, we found irregular outer contours in 26% of cases. The bowel wall was thickened in 82%. In acute phases, the bowel wall was thickened in 100%. Abscess and fistula as complications of inflammatory disease were present in 26 and 14% respectively. In ulcerative colitis, a target sign of the bowel wall was present in 40%, whereas in Crohn`s disease a homogeneous wall density was present in all but two cases. Reduced attenuation due to submucosal fat deposits was found in 16% and mucosal tunneling in 27% of cases with ulcerative colitis. Even if severe mucosal destructions were found, the outer contour of the gut was smooth and regular in 95% of the ulcerative colitis cases. CT can provide additional information on acuity, extent and complications in inflammatory bowel disease. In combination with conventional radiographic findings a three-step classification for Crohn`s disease and ulcerative colitis (early changes, acute and chronic phase) can be proposed. (orig./MG) [Deutsch] Wir untersuchten computertomographisch 109 Patienten mit 197 erkrankten Darmsegmenten. 81 Patienten litten an M. Crohn und 28 an Colitis ulcerosa. Die Diagnose wurde durch Kombination klinischer, endoskopischer, radiologischer und bioptischer Befunde gesichert. Drei Radiologen bewerteten die Computertomographien und verglichen die Ergebnisse mit den konventionell-radiologischen Befunden. Bei den Patienten mit M. Crohn fanden wir in 26% der Faelle eine irregulaere aeussere Darmwand. Eine Darmwandverdickung lag in 82% vor und fand sich regelmaessig in Darmabschnitten mit floriden Veraenderungen

  18. 实验性溃疡性结肠炎大鼠模型的建立%Establishment of experimental ulcerative colitis model in rats

    Institute of Scientific and Technical Information of China (English)

    吴小庚; 王爱磊; 张学明; 柴树花

    2011-01-01

    Objective To induce rat model of ulcerative colitis (UC) by TNBS/alcohol and to explore its similarity to human. Methods The UC animal models were established by TNBS/alcohol, and the general state,intestinal mucous,pathological and ultrastructure changes of model rats were observedin 1 week, 2 weeks and 7 weeks respectively,and the contents of TNF-α,IL-2 and IL-4 in serum were detected. Results The general state,intestinal mucous,pathological and ultrastructure changes of model rats with UC were similar to those of human being, forthermore, the changes of levels of serum TNF-α, IL-2, IL-4 were similar to those of human. Conclusion TNBS can seccessfully induce rat model of UC with high similarity to human, which has also the acute and chronic transition process and it is immunology model, so it can be used in the investigation of immunology.%目的 采用三硝基苯磺酸(TNBS)诱导大鼠溃疡性结肠炎动物模型,探讨与人溃疡性结肠炎(UC)的相似程度.方法 TNBS/乙醇法制作溃疡性结肠炎动物模型,分别于造模后1、3、7周3个时间段动态观察模型鼠的一般状态、结肠黏膜大体和病理及电镜变化.同时检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-2(IL-2)、白细胞介素-4(IL-4)含量.结果 大鼠的一般情况、大体病理及组织学病理及电镜变化均与人类溃疡性结肠炎类似,并且血清TNF-α、IL-2、IL-4含量变化亦与人类溃疡性结肠炎的变化基本一致.结论 TNBS可以成功诱导大鼠溃疡性结肠炎动物模型,一般情况、大体与病理表现与人UC的相似度高,有急、慢性转变过程等,而且是免疫学模型,可用于UC免疫学方面的研究.

  19. Thoracic epidural anesthesia attenuates hemorrhagic-induced splanchnic hypo-perfusion in post-resuscitation experimental hemorrhagic shock

    Directory of Open Access Journals (Sweden)

    Amir S Madjid

    2008-06-01

    Full Text Available The purpose of present study was to assess the effects of thoracic epidural anesthesia on splanchnic perfusion, bacterial translocation and histopathologic changes in experimental hemorrhagic shock in short-tailed macaques (Macaca nemestrina. Sixteen Macaca nemestrinas were randomly assigned to one of two groups i.e. the lidocaine group (n = 8, receiving general anesthesia plus lidocaine thoracic epidural anesthesia; and the saline group (n = 8, receiving general anesthesia alone as control. Hemorrhagic shock was induced by withdrawing blood gradually to a mean arterial pressure (MAP of 40 mm Hg, and maintained for 60 minutes. Animals were then resuscitated with their own blood and ringer lactate solution (RL. After resuscitation, epidural lidocaine 2% was given in the lidocaine group and saline in the control group. Resuscitation that was performed after one hour hemorrhagic shock, with hemodynamic variables and urine output returned to normal, revealed there was no improvement of splanchnic perfusion. PgCO2, P(g-aCO2, and pHi remained in critical value and tended to deteriorate in the saline group. Contrast to saline group, splanchnic perfusion in lidocaine group tended to improve. This condition was supported by the finding of less bacterial translocation and better histopathologic changes in lidocaine thoracic epidural anesthesia group than in saline group. This study concludes that lidocaine thoracic epidural anesthesia attenuates splachnic hypoperfusion in post-resuscitation hemorrhagic shock in Macaca nemestrina. (Med J Indones 2008; 17: 73-81Keywords: thoracic epidural anesthesia, lidocaine, hemorrhagic shock, splanchnic hypoperfusion, bacterial translocation

  20. Tracer attenuation in groundwater

    Science.gov (United States)

    Cvetkovic, Vladimir

    2011-12-01

    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  1. Experimental analysis of the structure attenuation characteristics on engine noise by pseudo cylinder pressure excitation; Giji tonaiatsu kashin ni yoru engine kozo no soon tokusei hyoka

    Energy Technology Data Exchange (ETDEWEB)

    Ozawa, H.; Nakada, T. [Isuzu Advanced Engineering Center, Tokyo (Japan)

    1997-10-01

    The engine structure attenuation has been experimentally analyzed by the newly developed in-cylinder excitation system. It can reproduce the complete cylinder pressure in non-running engine conditions by adopting the hydraulic and the piezoelectric actuator. The structure attenuation measured in this system has a good coincidence with the ones measured in actually engine operating conditions, meanwhile the current method, which applied only high frequency components as the excitation pressure, was shown to have the unsatisfied agreement. As a result, the proposed system has been concluded to be very useful to estimate the engine noise characteristics in non-running conditions. 4 refs., 11 figs., 1 tab.

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

    OpenAIRE

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

    2014-01-01

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

  3. Wild jujube polysaccharides protect against experimental inflammatory bowel disease by enabling enhanced intestinal barrier function.

    Science.gov (United States)

    Yue, Yuan; Wu, Shuangchan; Li, Zhike; Li, Jian; Li, Xiaofei; Xiang, Jin; Ding, Hong

    2015-08-01

    Dietary polysaccharides provide various beneficial effects for our health. We investigated the protective effects of wild jujube (Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou) sarcocarp polysaccharides (WJPs) against experimental inflammatory bowel disease (IBD) by enabling enhanced intestinal barrier function. Colitis was induced in rats by the intrarectal administration of TNBS. We found that WJPs markedly ameliorated the colitis severity, including less weight loss, decreased disease activity index scores, and improved mucosal damage in colitis rats. Moreover, WJPs suppressed the inflammatory response via attenuation of TNF-α, IL-1β, IL-6 and MPO activity in colitis rats. And then, to determine the effect of WJPs on the intestinal barrier, we measured the effect of WJPs on the transepithelial electrical resistance (TER) and FITC-conjugated dextran permeability in Caco-2 cell stimulation with TNF-α. We further demonstrated that the alleviation of WJPs to colon injury was associated with barrier function by assembly of tight junction proteins. Moreover, the effect of WJPs on TER was eliminated by the specific inhibitor of AMPK. AMPK activity was also up-regulated by WJPs in Caco-2 cell stimulation with TNF-α and in colitis rats. This study demonstrates that WJPs protect against IBD by enabling enhanced intestinal barrier function involving the activation of AMPK.

  4. Pegylated Arginine Deiminase Downregulates Colitis in Murine Models

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    Helieh S. Oz

    2012-01-01

    Full Text Available Arginine deiminase (ADI, an arginine-metabolizing enzyme involved in cell signaling, is dysregulated in multiple inflammatory diseases and cancers. We hypothesized that pegylated ADI (ADI-PEG provide protection against colitis. Methods. Dextran sodium sulfate colitis was induced in IL-10-deficient and BALB/c (WT mice. ADI-PEG was administered i.p., and inflammatory mediators and pathology were evaluated. Results. Acute colitis in mice was manifested by increases in inflammatory biomarkers, such as serum amyloid A (SAA, P<0.001, IL-12 p40, and disease index (3-Fold. In contrast, ADI-PEG significantly decreased clinical disease index, SAA levels, and inflammatory cytokines in blood as well as in colonic explants. Animals developed moderate (2.2±0.3 WT to severe (3.6±0.5 IL-10 deficient colonic pathology; and ADI-PEG treatment significantly improved the severity of colitis (P<0.05. Marked infiltration of CD68+ macrophages and iNOS expression were detected in colonic submucosa in colitic animals but not detected in ADI-PEG-treated animals. Conclusion. ADI-PEG attenuated inflammatory responses by suppression of macrophage infiltration and iNOS expression in colitic animals. ADI-PEG can serve as a potential therapeutic value in IBD.

  5. [Colitis associated with C. difficile].

    Science.gov (United States)

    Mironov, I L; Ratnikova, L I; Pirogov, D V; Mil'chenko, I B

    2014-01-01

    Pseudomembranous colitis (PMC), is characterized by acute onset, severe diarrhea, hypovolemic shock, toxic expansion of colon perforation, thrombus syndrome and without treatment in some cases leading to death of the patient. The paper describes a clinical case of pseudomembranous colitis in patients 35 years that developed on the background of the massive antibiotic therapy. The diagnosis was made only at autopsy. This case is unique, and dictates the need to inform doctors of practical health care of the complications of antibiotic therapy, such as pseudomembranous colitis.

  6. Erythropoietin attenuates pulmonary vascular remodeling in experimental pulmonary arterial hypertension through interplay between endothelial progenitor cells and heme-oxygenase

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    Rosa L.E. Loon

    2015-08-01

    Full Text Available BackgroundPulmonary arterial hypertension (PAH is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs and activation of the cytoprotective enzyme heme oxygenase-1 (HO1.MethodsRats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the presence or absence of the selective HO-activity-inhibitor tin-mesoporphyrin (SnMP. HO-activity, circulating EPCs and pulmonary vascular lesions were assessed after 3 weeks.ResultsIn PAH-rats, circulating EPCs were decreased and HO-activity was increased compared to control. EPO-treatment restored circulating EPCs and improved pulmonary vascular remodeling, as shown by a reduced wall thickness and occlusion rate of the intra-acinar vessels. Inhibition of HO-activity with SnMP aggravated PAH. Moreover, SnMP treatment abrogated EPO-induced amelioration of pulmonary vascular remodeling, while surprisingly further increasing circulating EPCs as compared with EPO alone.ConclusionsIn experimental PAH, EPO treatment restored the number of circulating EPC’s to control level, improved pulmonary vascular remodeling, and showed important interplay with HO-activity. Inhibition of increased HO-activity in PAH-rats exacerbated progression of pulmonary vascular remodeling, despite the presence of restored numbers of circulating EPC’s. We suggest that both EPO-induced HO1 and EPCs are promising targets to ameliorate the pulmonary vasculature in PAH.

  7. Acetyl-11-keto-beta-boswellic acid, a constituent of a herbal medicine from Boswellia serrata resin, attenuates experimental ileitis.

    Science.gov (United States)

    Krieglstein, C F; Anthoni, C; Rijcken, E J; Laukötter, M; Spiegel, H U; Boden, S E; Schweizer, S; Safayhi, H; Senninger, N; Schürmann, G

    2001-04-01

    The gum resin extract from Boswellia serrata (H15), an herbal product, was recently shown to have positive therapeutic effects in inflammatory bowel disease (IBD). However, the mechanisms and constituents responsible for these effects are poorly understood. This study examined the effect of the Boswellia extract and its single constituent acetyl-11-keto-beta-boswellic acid (AKBA) on leukocyte-endothelial cell interactions in an experimental model of IBD. Ileitis was induced by two subcutaneous injections of indomethacin (7.5 mg/kg) in Sprague-Dawley rats 24 h apart. Rats also received oral treatment with the Boswellia extract (H15) or AKBA at two different doses (low and high) equivalent to recommendations in human disease over 2 days. Controls received only the carriers NaHCO3 (subcutaneously) and tylose (orally). Effects of treatment were assessed by intravital microscopy in ileal submucosal venules for changes in the number of rolling and adherent leukocytes and by macroscopic and histological scoring. Increased leukocyte-endothelial cell adhesive interactions and severe tissue injury accompanied indomethacin-induced ileitis. Treatment with the Boswellia extract or AKBA resulted in a dose-dependent decrease in rolling (up to 90%) and adherent (up to 98%) leukocytes. High-dose Boswellia extract as well as both low- and high-dose AKBA significantly attenuated tissue injury scores. Oral therapy with the Boswellia extract or AKBA significantly reduces macroscopic and microcirculatory inflammatory features normally associated with indomethacin administration, indicating that the anti-inflammatory actions of the Boswellia extract in IBD may be due in part to boswellic acids such as AKBA.

  8. Erythropoietin Attenuates Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension through Interplay between Endothelial Progenitor Cells and Heme Oxygenase

    NARCIS (Netherlands)

    van Loon, Rosa Laura E; Bartelds, Beatrijs; Wagener, Frank A D T G; Affara, Nada; Mohaupt, Saffloer; Wijnberg, Hans; Pennings, Sebastiaan W C; Takens, Janny; Berger, Rolf M F

    2015-01-01

    BACKGROUND: Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progeni

  9. Crohn's Disease and Ulcerative Colitis: A Guide for Teachers and Other School Personnel

    Science.gov (United States)

    ... a clinical trial of experimental treatments. Interactive Disease Tracker Use GI Buddy to keep a daily log ... or a private dorm room. Participation in physical activities Young people with Crohn’s disease or ulcerative colitis ...

  10. An arachidonic acid-enriched diet does not result in more colonic inflammation as compared with fish oil- or oleic acid-enriched diets in mice with experimental colitis.

    Science.gov (United States)

    Ramakers, Julian D; Mensink, Ronald P; Verstege, Marleen I; te Velde, Anje A; Plat, Jogchum

    2008-08-01

    Fish oils (FO) - rich in EPA and DHA - may protect against colitis development. Moreover, inflammatory bowel disease patients have elevated colonic arachidonic acid (AA) proportions. So far, effects of dietary AA v. FO on colitis have never been examined. We therefore designed three isoenergetic diets, which were fed to mice for 6 weeks preceding and during 7 d dextran sodium sulfate colitis induction. The control diet was rich in oleic acid (OA). For the other two diets, 1.0 % (w/w) OA was exchanged for EPA+DHA (FO group) or AA. At 7 d after colitis induction, the AA group had gained weight (0.46 (sem 0.54) g), whereas the FO and OA groups had lost weight (- 0.98 (SEM 0.81) g and - 0.79 (SEM 1.05) g, respectively; P diet increased colonic AA content, but did not result in more colonic inflammation as compared with FO- and OA-enriched diets. As we only examined effects after 7 d and because the time point for evaluating effects seems to be important, the present results should be regarded as preliminary. Future studies should further elucidate differential effects of fatty acids on colitis development in time.

  11. [Pseudomembranous colitis: pathogenesis, prevention, treatment].

    Science.gov (United States)

    Zakharova, N V; Fil', T S

    2013-01-01

    The article reviews a pathogenesis of Pseudomembranous colitis. Questions of prevention and treatment of Clostridium difficile--associated diarrhea are shown by the Evidence-based medicine. There is an accent on the rational prescription of antibiotics.

  12. Mouse model of ulcerative colitis using trinitrobenzene sulfonic acid

    Directory of Open Access Journals (Sweden)

    Irfan Ahmad Rather

    2015-12-01

    Full Text Available Animal model of intestinal inflammation is of paramount significance that aids in discerning the pathologies underlying ulcerative colitis and Crohn’s disease, the two clinical presentations of inflammatory bowel disease. The 2,4,6-trinitrobenzene sulfonic acid (TNBS colitis model represents one such intestinal inflammation-prototype that is generated in susceptible strains of mice through intra-rectal instillation of compound TNBS. In this paper, we demonstrate the experimental induction of TNBS-mediated colitis in a susceptible strain of ICR mice. This can be done by the following steps: a acclimation, b induction and c observation. TNBS-mouse model provides the information in shortest possible time and simultaneously represents a cost effective and highly reproducible model method of studying the pathogenesis of inflammatory bowel disease.

  13. Management of pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Turner, Dan; Levine, Arie; Escher, Johanna C

    2012-01-01

    Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR......) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)....

  14. Tolerogenic dendritic cells specific for β2-glycoprotein-I Domain-I, attenuate experimental antiphospholipid syndrome.

    Science.gov (United States)

    Zandman-Goddard, Gisele; Pierangeli, Silvia S; Gertel, Smadar; Blank, Miri

    2014-11-01

    Tolerogenic dendritic cells (tDCs) have the potential to control the outcome of autoimmunity by modulating the immune response. The aim of this study was to uncover the tolerance efficacy attributed to beta-2-glycoprotein-I (β2GPI) tDCs or β2GPI domain-I (D-I) and domain-V (D-V)-tDCs in mice with antiphospholipid syndrome (APS). tDCs were pulsed with β2GPI or D-I or D-V derivatives. Our results revealed that β2GPI related tDCs phenotype includes CD80(high), CD86(high) CD40(high) MHC class II(high). The miRNA profiling encompass miRNA 23b(high), miRNA 142-3p(low) and miRNA 221(low). In addition the β2GPI related tDCs showed reduced secretion of IL-1β, IL-12 and IL-23. D-I tDCs treatment was more efficient than β2GPI tDCs in inducing of tolerance in APS mice, manifested by lowered titers of anti- β2GPI antibodies (Abs) and reduced percentage of fetal loss. Tolerance induction was accompanied by poor T cell response to β2GPI, high numbers of CD4 + CD25 + FOXP3 + T-regulatory cells (Treg), reduced levels of IFNγ, IL-17 and increased expression of IL-10 and TGFβ. Tolerance was successfully transferred by Treg cells from the tolerized mice to β2GPI immunized mice. We conclude that predominantly D-I-tDCs and β2GPI tDCs have the potential to attenuate experimental APS by induction of Treg cells, reduction of anti- β2GPI Abs titers and increased expression of anti-inflammatory cytokines. We suggest that β2-GPI-D-I-tDCs may offer a novel approach for developing therapy for APS patients.

  15. The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium

    Directory of Open Access Journals (Sweden)

    Kersting S

    2013-05-01

    Full Text Available Sabine Kersting,1* Volker Behrendt,1* Jonas Kersting,1 Kirstin Reinecke,3 Christoph Hilgert,1 Ingo Stricker,2 Thomas Herdegen,3 Monika S Janot,1 Waldemar Uhl,1 Ansgar M Chromik1 1Department of General and Visceral Surgery, St Josef Hospital, Ruhr University of Bochum, Bochum, Germany; 2Department of Pathology, Ruhr University of Bochum, Bochum, Germany; 3Institute of Experimental and Clinical Pharmacology, University Hospital of Schleswig-Holstein, Kiel, Germany *The two authors Sabine Kersting and Volker Behrendt contributed equally to this work Purpose: The c-Jun N-terminal kinases (JNK are involved in the activation of T cells and the synthesis of proinflammatory cytokines. Several studies have established the relevance of the JNK pathway in inflammatory bowel diseases. The present study analyzed the therapeutic effect of D-JNKI-1, a specific JNK-inhibiting peptide, in a low-dose dextran sulfate sodium (DSS model of chronic colitis. Methods: DSS colitis was induced in female C57/BL6 mice by cyclic administration using different concentrations of DSS (1.0% and 1.5%. Mice in the intervention groups received subcutaneous administration of 1 µg/kg D-JNKI-1 on days 2, 12, and 22. They were monitored daily to assess the severity of colitis, body weight, stool consistency, and the occurrence of occult blood or gross rectal bleeding using evaluation of the disease activity index. The animals were sacrificed after 30 days, and the inflamed intestine was histologically evaluated using a crypt damage score. Immunohistochemical quantification of CD4+ and CD8+ cells was also carried out. Results: Administration of 1 µg/kg D-JNKI-1 resulted in a significant decrease in the disease activity index (P = 0.013 for 1.0% DSS; P = 0.007 for 1.5% DSS. As a mild form of colitis was induced, histological examination did not show any distinct damage to the mucosa and crypts. However, expression of CD4+ and CD8+ cells was reduced in mice treated with D-JNKI-1 (not

  16. Atypical disease phenotypes in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Levine, Arie; de Bie, Charlotte I; Turner, Dan

    2013-01-01

    Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...

  17. Microscopic Colitis with Macroscopic Endoscopic Findings

    OpenAIRE

    Atif Saleem; Brahmbhatt, Parag A.; Sarah Khan; Mark Young; LeSage, Gene D.

    2013-01-01

    Microscopic Colitis (MC) is characterized by chronic watery diarrhea, grossly normal appearing colonic mucosa during conventional white light endoscopy, and biopsy showing microscopic inflammation. We report a case of collagenous colitis with gross endoscopic findings.

  18. Effect of Bifidobacterium on expression of inflammatory cytokine in experimental colitis rats%双歧杆菌对实验性结肠炎中趋化因子的影响

    Institute of Scientific and Technical Information of China (English)

    吴正祥; 丁洁; 杨九华; 吴强; 杨枫

    2011-01-01

    Objective To observe the preventive and therapeutic effect of Bifidobacterium on experimental rats with 2,4, 6-trinitrobenzene sulfonic acid (TNBS)/ethanol induced colitis.Methods Forty rats were randomly divided into four groups (n = 10): normal control group (group N) ,model group (group M ), Bifidobacterium prevention group (group A),and Bifidobacterium treatment group (group B).The colitis model of rats was established with TNBS/ethanol.Group A was fed with Bifidobacterium 0.1 mL for 7 days before to be molded, group B was given Bifidobacterium 0.1 mL after to be molded (the solution concentration of Bifidobacterium is 1 × 108 cfu/mL), and group N and group M were given 2 mL normal saline.After continuous administration for 14 days, the colonic inflammation including disease activity index (DAI),colonic macroscopic damage index (CMDI) and tissue damage index (TDI) were observed, the expression of CCL20 and CCR6 in the colon tissues of rats were detected by immunohistochemical method, the levels of CCL20, CCR6, TNF-α and IL-10 in serum were detected by ELISA.Results Compared with group M, the scores of DAI, CMDI and TDI, and the expressions of CCL20 and CCR6 in the colon tissues and the serum levels of CCL20, CCR6 and TNF-α significantly decreased in group A and group B (P <0.01 ), while the serum level of IL-10 significantly increased (P <0.01 ).But the group A and group B had no significant difference.Conclusion Bifidobacterium possiblely produces prevention and treatment effect in experimental colitis rats by regulating the dynamic balance between proinflammatory and inflammation cytokines.Furthermore, Bifidobacterium in advance can improve the effectiveness and perform better.%目的 观察双歧杆菌在三硝基苯磺酸(TNBS)/乙醇诱导的实验性结肠炎的作用,并探讨其作用机制.方法 40只SPF级SD大鼠随机均分为正常组(N组)、模型组(M组)、双歧杆菌干预组(双歧杆菌预防性应用组:A组;双歧杆菌治疗

  19. Fucoidan Extracts Ameliorate Acute Colitis.

    Science.gov (United States)

    Lean, Qi Ying; Eri, Rajaraman D; Fitton, J Helen; Patel, Rahul P; Gueven, Nuri

    2015-01-01

    Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are an important cause of morbidity and impact significantly on quality of life. Overall, current treatments do not sustain a long-term clinical remission and are associated with adverse effects, which highlight the need for new treatment options. Fucoidans are complex sulphated, fucose-rich polysaccharides, found in edible brown algae and are described as having multiple bioactivities including potent anti-inflammatory effects. Therefore, the therapeutic potential of two different fucoidan preparations, fucoidan-polyphenol complex (Maritech Synergy) and depyrogenated fucoidan (DPF) was evaluated in the dextran sulphate sodium (DSS) mouse model of acute colitis. Mice were treated once daily over 7 days with fucoidans via oral (Synergy or DPF) or intraperitoneal administration (DPF). Signs and severity of colitis were monitored daily before colons and spleens were collected for macroscopic evaluation, cytokine measurements and histology. Orally administered Synergy and DPF, but not intraperitoneal DPF treatment, significantly ameliorated symptoms of colitis based on retention of body weight, as well as reduced diarrhoea and faecal blood loss, compared to the untreated colitis group. Colon and spleen weight in mice treated with oral fucoidan was also significantly lower, indicating reduced inflammation and oedema. Histological examination of untreated colitis mice confirmed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and oedema, while all aspects of this pathology were alleviated by oral fucoidan. Importantly, in this model, the macroscopic changes induced by oral fucoidan correlated significantly with substantially decreased production of at least 15 pro-inflammatory cytokines by the colon tissue. Overall, oral fucoidan preparations significantly reduce the inflammatory pathology associated with DSS-induced colitis and could therefore represent

  20. RF-MEMS for future mobile applications: experimental verification of a reconfigurable 8-bit power attenuator up to 110 GHz

    Science.gov (United States)

    Iannacci, J.; Tschoban, C.

    2017-04-01

    RF-MEMS technology is proposed as a key enabling solution for realising the high-performance and highly reconfigurable passive components that future communication standards will demand. In this work, we present, test and discuss a novel design concept for an 8-bit reconfigurable power attenuator, manufactured using the RF-MEMS technology available at the CMM-FBK, in Italy. The device features electrostatically controlled MEMS ohmic switches in order to select/deselect the resistive loads (both in series and shunt configuration) that attenuate the RF signal, and comprises eight cascaded stages (i.e. 8-bit), thus implementing 256 different network configurations. The fabricated samples are measured (S-parameters) from 10 MHz to 110 GHz in a wide range of different configurations, and modelled/simulated with Ansys HFSS. The device exhibits attenuation levels (S21) in the range from  ‑10 dB to  ‑60 dB, up to 110 GHz. In particular, S21 shows flatness from 15 dB down to 3–5 dB and from 10 MHz to 50 GHz, as well as fewer linear traces up to 110 GHz. A comprehensive discussion is developed regarding the voltage standing wave ratio, which is employed as a quality indicator for the attenuation levels. The margins of improvement at design level which are needed to overcome the limitations of the presented RF-MEMS device are also discussed.

  1. The anti-inflammatory potential of phenolic compounds in grape juice concentrate (G8000™) on 2,4,6-trinitrobenzene sulphonic acid-induced colitis.

    Science.gov (United States)

    Paiotti, Ana Paula Ribeiro; Neto, Ricardo Artigiani; Marchi, Patrícia; Silva, Roseane Mendes; Pazine, Vanessa Lima; Noguti, Juliana; Pastrelo, Mauricio Mercaldi; Gollücke, Andréa Pittelli Boiago; Miszputen, Sender Jankiel; Ribeiro, Daniel Araki

    2013-09-28

    Chronic inflammatory bowel disease is characterised by an up-regulation of the synthesis and release of a variety of pro-inflammatory mediators leading to excessive tissue injury. Flavonoids are able to inhibit enzymes and/or due to their antioxidant properties regulate the immune response. The goal of the present study was to evaluate the mechanisms of action of phenolic compounds present in grape juice on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. A total of forty-one male Wistar rats were randomised into seven groups: negative control group; TNBS non-treated induced colitis; 2% grape juice control group; 1% grape juice 24 h after TNBS colitis induction; 1% grape juice on day 7 after colitis induction; 2% grape juice 24 h after colitis induction; 2% grape juice on day 7 after colitis induction. The 1% grape juice-treated induced colitis group showed marked clinical improvement when compared with the TNBS-induced colitis group. Rats that received 1% grape juice, on day 7 after colitis induction, presented reduced intensity of macroscopic and histological scores. Statistically significant differences (P,0·05) of TNF-a and inducible NO synthase mRNA expression were detected in the groups treated with grape juice at the 1% dose after inducing experimental colitis when compared with the TNBS group. Grape juice reduced the noxious effects induced by colitis caused by TNBS, especially at the 1% dose.

  2. Recent advances in the management of radiation colitis

    Institute of Scientific and Technical Information of China (English)

    Jannis Kountouras; Christos Zavos

    2008-01-01

    Radiation colitis,an insidious,progressive disease of increasing frequency,develops 6 mo to 5 years after regional radiotherapy for malignancy,owing to the deleterious effects of the latter on the colon and the small intestine.When dealing with radiation colitis and its complications,the most conservative modality should be employed because the areas of intestinal injury do not tend to heal.Acute radiation colitis is mostly selflimited,and usually,only supportive management is required.Chronic radiation colitis,a poorly predictable progressive disease,is considered as a precancerous lesion;radiation-associated malignancy has a tendency to be diagnosed at an advanced stage and to bear a dismal prognosis.Therefore,management of chronic radiation colitis remains a major challenge owing to the progressive evolution of the disease,including development of fibrosis,endarteritis,edema,fragility,perforation,partial obstruction,and cancer.Patients are commonly managed conservatively.Surgical intervention is difficult to perform because of the extension of fibrosis and alterations in the gut and mesentery,and should be reserved for intestinal obstruction,perforation,fistulas,and severe bleeding.Owing to the difficulty in managing the complications of acute and chronic radiation colitis,particular attention should be focused onto the prevention strategies.Uncovering the fibrosis mechanisms and the molecular events underlying radiation bowel disease could lead to the introduction of new therapeutic and/or preventive approaches.A variety of novel,mostly experimental,agents have been used mainly as a prophylaxis,and improvements have been made in radiotherapy delivery,including techniques to reduce the amount of exposed intestine in the radiation field,as a critical strategy for prevention.

  3. Simultaneous Determination of Three Furanocoumarins by UPLC/MS/MS: Application to Pharmacokinetic Study of Angelica dahurica Radix after Oral Administration to Normal and Experimental Colitis-Induced Rats

    Directory of Open Access Journals (Sweden)

    Youn-Hwan Hwang

    2017-03-01

    Full Text Available In traditional oriental medicine, Angelica dahurica Radix (ADR is used in the treatment of gastrointestinal, respiratory, neuromuscular, and dermal disorders. We evaluated the pharmacokinetic profiles of oxypeucedanin, imperatorin, and isoimperatorin, major active ingredients of ADR, in normal and 2,4,6-trinitrobenzene sulfonic acid (TNBS-induced colitis rats. A rapid, sensitive, and validated UPLC/MS/MS method was established for evaluating the pharmacokinetics of three furanocoumarins. After oral administration of ADR (0.5 and 1.0 g/kg, blood samples were collected periodically from the tail vein. In colitis rats, the time to reach the peak concentration (Tmax of imperatorin and isoimperatorin was significantly delayed (p < 0.05. Lower peak plasma concentrations (Cmax and longer mean residence times for all furanocoumarins were also observed (p < 0.05 compared with normal rats. There was no significant difference in the area under the plasma concentration–time curve or elimination half-lives. Thus, the delayed Tmax and decreased Cmax, with no influence on the elimination half-life, could be colitis-related changes in the drug-absorption phase. Therefore, the prescription and use of ADR in colitis patients should receive more attention.

  4. Psychological stress promotes neutrophil infiltration in colon tissue through adrenergic signaling in DSS-induced colitis model.

    Science.gov (United States)

    Deng, Que; Chen, Hongyu; Liu, Yanjun; Xiao, Fengjun; Guo, Liang; Liu, Dan; Cheng, Xiang; Zhao, Min; Wang, Xiaomeng; Xie, Shuai; Qi, Siyong; Yin, Zhaoyang; Gao, Jiangping; Chen, Xintian; Wang, Jiangong; Guo, Ning; Ma, Yuanfang; Shi, Ming

    2016-10-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition. Psychological stress has been postulated to affect the clinical symptoms and recurrence of IBD. The exact molecular mechanisms are not fully understood. In the present study, we demonstrate that psychological stress promotes neutrophil infiltration into colon tissues in dextran sulfate sodium (DSS)-induced colitis model. The psychological stress resulted in abnormal expression of the proinflammatory cytokines (IL-1β, IL-6, IL-17A, and IL-22) and neutrophil chemokines (CXCL1 and CXCL2) and overactivation of the STAT3 inflammatory signaling pathway. Under chronic unpredictable stress, the adrenergic nervous system was markedly activated, as the expression of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, in bone marrow and colonic epithelium was enhanced, especially in the myenteric ganglia. The β-AR agonist isoproterenol mimicked the effects of psychological stress on neutrophilia, neutrophil infiltration, and colonic damage in DSS-induced colitis. The β1-AR/β2-AR inhibitor propranolol reduced the numbers of the neutrophils in the circulation, suppressed neutrophil infiltration into colonic tissues, and attenuated the colonic tissue damage promoted by chronic stress. Propranolol also abolished stress-induced upregulation of proinflammatory cytokines and neutrophil chemokines. Our data reveal a close linkage between the β1-AR/β2-AR activation and neutrophil trafficking and also suggest the critical roles of adrenergic nervous system in exacerbation of inflammation and damage of colonic tissues in experimental colitis. The current study provides a new insight into the mechanisms underlying the association of psychological stress with excessive inflammatory response and pathophysiological consequences in IBD. The findings also suggest a potential application of neuroprotective agents to prevent relapsing immune activation in the treatment of IBD.

  5. Therapeutic treatment with a novel hypoxia-inducible factor hydroxylase inhibitor (TRC160334) ameliorates murine colitis

    Science.gov (United States)

    Gupta, Ram; Chaudhary, Anita R; Shah, Binita N; Jadhav, Avinash V; Zambad, Shitalkumar P; Gupta, Ramesh Chandra; Deshpande, Shailesh; Chauthaiwale, Vijay; Dutt, Chaitanya

    2014-01-01

    Background and aim Mucosal healing in inflammatory bowel disease (IBD) can be achieved by improvement of intestinal barrier protection. Activation of hypoxia-inducible factor (HIF) has been identified as a critical factor for barrier protection during mucosal insult and is linked with improvement in symptoms of colitis. Although prophylactic efficacy of HIF hydroxylase inhibitors in murine colitis have been established, its therapeutic efficacy in clinically relevant therapeutic settings have not been established. In the present study we aim to establish therapeutic efficacy of TRC160334, a novel HIF hydroxylase inhibitor, in animal models of colitis. Methods The efficacy of TRC160334 was evaluated in two different mouse models of colitis by oral route. A prophylactic efficacy study was performed in a 2,4,6-trinitrobenzene sulfonic acid-induced mouse model of colitis representing human Crohn’s disease pathology. Additionally, a therapeutic efficacy study was performed in a dextran sulfate sodium-induced mouse model of colitis, a model simulating human ulcerative colitis. Results TRC160334 treatment resulted in significant improvement in disease end points in both models of colitis. TRC160334 treatment resulted into cytoprotective heatshock protein 70 induction in inflamed colon. TRC160334 successfully attenuated the rate of fall in body weight, disease activity index, and macroscopic and microscopic scores of colonic damage leading to overall improvement in study outcome. Conclusion Our findings are the first to demonstrate that therapeutic intervention with a HIF hydroxylase inhibitor ameliorates IBD in disease models. These findings highlight the potential of TRC160334 for its clinical application in the treatment of IBD. PMID:24493931

  6. Therapeutic treatment with a novel hypoxia-inducible factor hydroxylase inhibitor (TRC160334 ameliorates murine colitis

    Directory of Open Access Journals (Sweden)

    Gupta R

    2014-01-01

    Full Text Available Ram Gupta,1 Anita R Chaudhary,2 Binita N Shah,1 Avinash V Jadhav,3 Shitalkumar P Zambad,1 Ramesh Chandra Gupta,4 Shailesh Deshpande,4 Vijay Chauthaiwale,4 Chaitanya Dutt4 1Department of Pharmacology, 2Cellular and Molecular Biology, 3Preclinical Safety Evaluation, 4Discovery, Torrent Research Centre, Torrent Pharmaceuticals Ltd, Gandhinagar, Gujarat, India Background and aim: Mucosal healing in inflammatory bowel disease (IBD can be achieved by improvement of intestinal barrier protection. Activation of hypoxia-inducible factor (HIF has been identified as a critical factor for barrier protection during mucosal insult and is linked with improvement in symptoms of colitis. Although prophylactic efficacy of HIF hydroxylase inhibitors in murine colitis have been established, its therapeutic efficacy in clinically relevant therapeutic settings have not been established. In the present study we aim to establish therapeutic efficacy of TRC160334, a novel HIF hydroxylase inhibitor, in animal models of colitis. Methods: The efficacy of TRC160334 was evaluated in two different mouse models of colitis by oral route. A prophylactic efficacy study was performed in a 2,4,6-trinitrobenzene sulfonic acid-induced mouse model of colitis representing human Crohn's disease pathology. Additionally, a therapeutic efficacy study was performed in a dextran sulfate sodium-induced mouse model of colitis, a model simulating human ulcerative colitis. Results: TRC160334 treatment resulted in significant improvement in disease end points in both models of colitis. TRC160334 treatment resulted into cytoprotective heatshock protein 70 induction in inflamed colon. TRC160334 successfully attenuated the rate of fall in body weight, disease activity index, and macroscopic and microscopic scores of colonic damage leading to overall improvement in study outcome. Conclusion: Our findings are the first to demonstrate that therapeutic intervention with a HIF hydroxylase inhibitor

  7. Microscopic colitis: Is it a spectrum of inflammatory bowel disease?

    OpenAIRE

    Jegadeesan, Ramprasad; Liu, Xiuli; Pagadala, Mangesh R.; Gutierrez, Norma; Butt, Mujtaba; Navaneethan, Udayakumar

    2013-01-01

    Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerati...

  8. Experimental investigation of wave-driven pore-water pressure and wave attenuation in a sandy seabed

    Directory of Open Access Journals (Sweden)

    Jisheng Zhang

    2016-06-01

    Full Text Available Wave–seabed interaction has become a big concern of coastal researchers and engineers in the past decades as it may largely contribute to the seabed instability and failure of marine foundations. A series of laboratory experiments are carried out in a wave flume to study the wave-driven pore-water pressure in a sandy seabed and the attenuation of wave height. Waves propagating over a sandy seabed lead to oscillatory excess pore-water pressures within the porous seabed. Amplitude of pore-water pressure within the seabed decreases toward the bottom. A phase lag of pore-water pressure is clearly observed, and it contributes to net upward pressure related to seabed instability. Height of the incident wave is reduced as part of wave energy is dissipated by bottom friction, and a maximum attenuation of the incident wave height is up to 7.23% in the experiments. The influences of wave period and height of the incident wave on pore-water pressure and wave attenuation are also analyzed and discussed.

  9. Confocal laser endomicroscopy in ulcerative colitis

    DEFF Research Database (Denmark)

    Karstensen, John Gásdal; Săftoiu, Adrian; Brynskov, Jørn

    2016-01-01

    was to correlate colonic confocal laser endomicroscopy (CLE) in ulcerative colitis with histopathology and macroscopic appearance before and after intensification of medical treatment. METHODS: Twenty-two patients with ulcerative colitis in clinical relapse and 7 control subjects referred for colonoscopy were...... colitis compared with inactive ulcerative colitis...... is an emerging endoscopic technique that reproducibly identifies mucosal changes in ulcerative colitis. With the exception of crypt changes, endomicroscopic features appear to improve slowly with time after medical treatment. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01684514.)....

  10. Arctigenin but not arctiin acts as the major effective constituent of Arctium lappa L. fruit for attenuating colonic inflammatory response induced by dextran sulfate sodium in mice.

    Science.gov (United States)

    Wu, Xin; Yang, Yan; Dou, Yannong; Ye, Jun; Bian, Difei; Wei, Zhifeng; Tong, Bei; Kong, Lingyi; Xia, Yufeng; Dai, Yue

    2014-12-01

    The crude powder of the fruit of Arctium lappa L. (ALF) has previously been reported to attenuate experimental colitis in mice. But, its main effective ingredient and underlying mechanisms remain to be identified. In this study, ALF was extracted with ethanol, and then successively fractionated into petroleum ether, ethyl acetate, n-butanol and water fraction. Experimental colitis was induced by dextran sulfate sodium (DSS) in mice. Among the four fractions of ALF, the ethyl acetate fraction showed the most significant inhibition of DSS-induced colitis in mice. The comparative studies of arctigenin and arctiin (the two main ingredients of ethyl acetate fraction) indicated that arctigenin rather than arctiin could reduce the loss of body weight, disease activity index and histological damage in the colon. Arctigenin markedly recovered the loss of intestinal epithelial cells (E-cadherin-positive cells) and decreased the infiltration of neutrophils (MPO-positive cells) and macrophages (CD68-positive cells). Arctigenin could down-regulate the expressions of TNF-α, IL-6, MIP-2, MCP-1, MAdCAM-1, ICAM-1 and VCAM-1 at both protein and mRNA levels in colonic tissues. Also, it markedly decreased the MDA level, but increased SOD activity and the GSH level. Of note, the efficacy of arctigenin was comparable or even superior to that of the positive control mesalazine. Moreover, it significantly suppressed the phosphorylation of MAPKs and the activation of NF-κB, including phosphorylation of IκBα and p65, p65 translocation and DNA binding activity. In conclusion, arctigenin but not arctiin is the main active ingredient of ALF for attenuating colitis via down-regulating the activation of MAPK and NF-κB pathways.

  11. Therapeutic immunization with radio-attenuated Leishmania parasites through i.m. route revealed protection against the experimental murine visceral leishmaniasis.

    Science.gov (United States)

    Datta, Sanchita; Manna, Madhumita; Khanra, Supriya; Ghosh, Moumita; Bhar, Radhaballav; Chakraborty, Anindita; Roy, Syamal

    2012-07-01

    After our promising results from prophylactic and therapeutic study (i.p. route) with the radio-attenuated Leishmania donovani parasites against experimental murine visceral leishmaniasis, we prompted to check their therapeutic efficacy through i.m route. BALB/c mice were infected with highly virulent L. donovani parasites. After 75 days, mice were treated with gamma (γ)-irradiated parasites. A second therapeutic immunization was given after 15 days of first immunization. The protection against kala-azar was estimated with the reduction of Leishman-Donovan unit from spleen and liver that scored up to 80% and 93%, respectively, while a twofold increase in nitric oxide (NO) and reactive oxygen species (ROS) productions has been observed in the immunized groups of animals. These groups of mice also showed disease regression by skewing Th2 cytokines (IL-10) towards Th1 cytokine (IFN-γ) bias along with the increased generation of NO and ROS, while the infected control group of mice without such treatment surrendered to the disease. Establishment of Th1 ambience in the treated groups has also been supported from the measured antileishmanial antibody IgG subsets (IgG2a and IgG1) with higher anti-soluble Leishmania antigen-specific IgG2a titer. As seen in our previous studies, doses of attenuation by γ-radiation should be taken into serious consideration. Attenuation of parasites at 50 Gy of absorbed dose of gamma rays has not worked well. Thus, therapeutic use of L. donovani parasites radio-attenuated at particular doses can be exploited as a promising vaccine agent. Absence of any adjuvant may increase its acceptability as vaccine candidate further.

  12. Diagnostic imaging advances in murine models of colitis.

    Science.gov (United States)

    Brückner, Markus; Lenz, Philipp; Mücke, Marcus M; Gohar, Faekah; Willeke, Peter; Domagk, Dirk; Bettenworth, Dominik

    2016-01-21

    Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary non-invasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography, discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.

  13. Spinal histamine in attenuation of mechanical hypersensitivity in the spinal nerve ligation-induced model of experimental neuropathy.

    Science.gov (United States)

    Wei, Hong; Viisanen, Hanna; You, Hao-Jun; Pertovaara, Antti

    2016-02-05

    Here we studied whether and through which mechanisms spinal administration of histamine dihydrochloride (histamine) attenuates pain behavior in neuropathic animals. Experiments were performed in rats with spinal nerve ligation-induced neuropathy and a chronic intrathecal catheter for spinal drug delivery. Mechanical hypersensitivity was assessed with monofilaments while radiant heat was used for assessing nociception. Ongoing neuropathic pain and its attenuation by histamine was assessed using conditioned place-preference test. Following spinal administration, histamine at doses 0.1-10µg produced a dose-related mechanical antihypersensitivity effect. With prolonged treatment (twice daily 10µg for five days), the antihypersensitivity effect of spinal histamine was reduced. In place-preference test, neuropathic animals preferred the chamber paired with histamine (10µg). Histamine (10µg) failed to influence heat nociception in neuropathic animals or mechanically induced pain behavior in a group of healthy control rats. Histamine-induced mechanical antihypersensitivity effect was prevented by spinal pretreatment with zolantidine (histamine H2 receptor antagonist), prazosine (α1-adrenoceptor antagonist) and bicuculline (γ-aminobutyric acid subtype A, GABA(A), receptor antagonist), but not by pyrilamine (histamine H1 receptor antagonist), atipamezole (α2-adrenoceptor antagonist), or raclopride (dopamine D2 receptor antagonist). A-960656, a histamine H3 receptor antagonist alone that presumably increased endogenous histamine levels reduced hypersensitivity. Additionally, histamine prevented central (presumably postsynaptically-induced) facilitation of hypersensitivity induced by N-methyl-d-aspartate. The results indicate that spinal histamine at the dose range of 0.1-10µg selectively attenuates mechanical hypersensitivity and ongoing pain in neuropathy. The spinal histamine-induced antihypersensitivity effect involves histamine H2 and GABA(A) receptors and

  14. Calibration of Recoil-In-Vacuum attenuations from first principles: comparison with recent experimental data on Fe isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Stone, Nicholas James, E-mail: n.stone@physics.ox.ac.uk; Stone, Jirina Rikovska [University of Tennessee, Department of Physics and Astronomy (United States); Stuchbery, Andrew E. [Australian National University, Department of Nuclear Physics (Australia); Jonsson, Per [Malmo University (Sweden)

    2015-04-15

    Precession of aligned nuclear spin systems in ions recoiling from the target into vacuum (RIV) with consequent attenuation of angular distributions of emitted radiation is, in principle, a versatile method for measurement of g-factors of nuclear excited states of lifetimes in the pico-second range (Stone et al., Phys. Rev. Lett., 94, 192501, 2005 and Stuchbery and Stone, Phys. Rev. C, 76, 034307, 2007). Calibration of the observed attenuations has been achieved in favourable cases through comparison with measurements on states having previously known g-factors and lifetimes. The general lack of suitable states with known g-factors has limited application of the RIV method. This paper concerns the present status of efforts to describe the states of excited ions recoiling into vacuum in detail so that the average interaction can be estimated with useful precision from a-priori theory. The calculations use the GRASP2K package (Froese-Fischer et al. 1997 and Jonsson, Comp. Phys. Comm., 177, 597, 2007 & 184, 2197, 2013) to obtain, for each recoiling ion change state, the individual possible electronic states, their configurations, lifetimes and hyperfine interactions. It is assumed that all possible ionic states are produced, up to a chosen excitation energy. This energy is selected to approximate the energy at which all states have lifetimes far shorter than the nuclear state of interest. It is further assumed that the ionic state total electron angular momenta are randomly oriented in space. The first estimates of the average attenuation of emission distributions, as a function of the product g τ of the nuclear state g-factor and mean lifetime, used an averaged precession frequency obtained neglecting transitions between electronic states. Improved calculations, which include such transitions, are described.

  15. 硝酸酯在小鼠急性实验性结肠炎中的治疗作用%Therapeutic effect of nitrate on dextran sulfate sodium induced acute experimental colitis in mice

    Institute of Scientific and Technical Information of China (English)

    肖军华; 沈佳庆; 宋允娜; 郑萍

    2012-01-01

    目的 观察硝酸酯对小鼠急性实验性结肠炎的疗效.方法 将40只BALB/c小鼠均分为模型组和治疗组,模型组予4%葡聚糖硫酸钠(DSS)溶液,治疗组予4%DSS溶液和1.5 g/L硝酸酯溶液,均连续饮用7d.对小鼠疾病活动指数(DAI)进行评分.取小鼠结肠组织进行苏木精-伊红染色和髓过氧化物酶(MPO)免疫组织化学染色并进行观察.分别用MPO和一氧化氮检测试剂盒检测结肠组织MPO和一氧化氮活性.统计学处理采用t检验.结果 第6和第7天治疗组和模型组的DAI差异有统计学意义(t=5.12和6.72,P=0.012和0.008).第7天时模型组组织学评分(2.5±0.5)高于治疗组(1.9±0.4),差异有统计学意义(t=3.82,P<0.01).与模型组相比,治疗组小鼠结肠组织病理损伤明显减轻,中性粒细胞浸润减少.第7天时模型组MPO活性、NO2-浓度、NO3-浓度分别为(2.8±0.6) U/g、(10.4±4.3) mmol/g、(100.3±50.1)mmol/g,治疗组则分别为(1.5±0.3)U/g、(17.5±7.0)mmol/g、(190.7±85.3) mmol/g,差异均有统计学意义(t=11.23、3.81、4.50,P均<0.01).结论 硝酸酯可减轻DSS诱导的小鼠急性实验性结肠炎.%Objective To investigate the effect of nitrate on acute experimental colitis in mice.Methods A total of 40 BALB/c mice were evenly divided into model group and treatment group.Model group were fed with 4% dextran sulfate sodium (DSS) solution and treatment group were given 4% DSS solution and nitrate (1.5 g/L) for seven days.The disease activity index (DAI) of mice was scored.The colon tissue of mice was taken for hematoxylin-eosin staining and myeloperoxidase (MPO)immunohistochemical staining observation.The MPO and activity of nitric oxide in colon tissue were measured by MPO and nitric oxide detecting kit.The data were analyzed by t test.Results At the 6th day and 7th day,the difference of DAI between treatment group and model group was statistically significant (t=5.12 and 6.72,P=0.012 and 0.008).At the 7th day,the tissue

  16. Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Kapil Suchal

    2016-01-01

    Full Text Available Kaempferol (KMP, a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p. was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB, inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3, TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2. In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway.

  17. Mucosal healing in ulcerative colitis

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  18. Haemorrhagic Colitis Caused by Dasatinib

    Directory of Open Access Journals (Sweden)

    Nishant Patodi

    2012-01-01

    Full Text Available Gastrointestinal bleeding appears to be a common adverse event associated with dasatinib therapy. Here we present a case of a 59-year-old man with chronic myeloid leukaemia (CML developing the rarest complication of haemorrhagic colitis with dasatinib therapy which resolved rapidly after treatment withdrawal.

  19. Haemorrhagic Colitis Caused by Dasatinib

    Science.gov (United States)

    Patodi, Nishant; Sagar, Nidhi; Rudzki, Zbigniew; Langman, Gerald; Sharma, Naveen

    2012-01-01

    Gastrointestinal bleeding appears to be a common adverse event associated with dasatinib therapy. Here we present a case of a 59-year-old man with chronic myeloid leukaemia (CML) developing the rarest complication of haemorrhagic colitis with dasatinib therapy which resolved rapidly after treatment withdrawal. PMID:23316400

  20. Olanzapine-induced ischemic colitis

    Directory of Open Access Journals (Sweden)

    Esteban Sáez-González

    Full Text Available Background: Ischemic colitis (IC is an uncommon adverse event associated with antipsychotic agents, more commonly found with phenothiazine drugs and atypical neuroleptics such as clozapine. The risk of developing ischemic colitis increases when anticholinergic drugs are associated. Case report: We report the case of a 38-year-old woman with a history of schizoaffective disorder who had been on chronic quetiapine for 3 years, and presented to the ER because of diarrhea for 5 days. Four months previously, olanzapine had been added to her psychiatric drug regimen. Physical examination revealed abdominal distension with abdominal tympanic sounds and tenderness. Emergency laboratory tests were notable for increased acute phase reagents. Tomography revealed a concentric thickening of the colonic wall in the transverse, descending and sigmoid segments, with no signs of intestinal perforation. Colonoscopy demonstrated severe mucosal involvement from the sigmoid to the hepatic flexure, with ulcerations and fibrinoid exudate. Biopsies confirmed the diagnosis of ischemic colitis. The only relevant finding in her history was the newly added drug to her baseline regimen. An adverse effect was suspected because of its anticholinergic action at the intestinal level, and the drug was withdrawn. After 6 months of follow-up clinical, laboratory and endoscopic recovery was achieved. Discussion: Antipsychotic medication should be considered as a potential cause of ischemic colitis, particularly atypical antipsychotics such as clozapine and olanzapine; despite being uncommon, this adverse event may result in high morbidity and mortality.

  1. Mucosal healing in ulcerative colitis

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  2. Kolorektal cancerudvikling ved colitis ulcerosa

    DEFF Research Database (Denmark)

    Kallesøe, Jane; Langholz, E.; Frisch, Morten

    2010-01-01

    Ulcerative colitis (UC) is believed to carry a predisposition to colorectal cancer (CRC) development. International clinical guidelines suggest that UC patients should have a colonoscopy performed every year or up to every third year from approximately eight years after diagnosis for early...

  3. [Ulcerative colitis and cytomegalovirus infection].

    Science.gov (United States)

    Tárraga Rodríguez, I; Ferreras Fernández, P; Vicente Gutiérrez, M; de Arriba, J J; García Mouriño, M L

    2003-02-01

    Colitis ulcerous and citomegalovirus infection association have been reported in medical literature in sometimes, althougth this prevalence have lately increased. We report a case record of this association and do a review of this subject. It is not clear what factors are involved in this association, being necessary hore studies to know them.

  4. Severity of DSS-induced colitis is reduced in Ido1-deficient mice with down-regulation of TLR-MyD88-NF-kB transcriptional networks.

    Science.gov (United States)

    Shon, Woo-Jeong; Lee, Young-Kwan; Shin, Ji Hee; Choi, Eun Young; Shin, Dong-Mi

    2015-11-27

    Indoleamine 2,3 -dioxygenase 1 (IDO1) catalyzes L-tryptophan to kynurenine in the first and rate-limiting step of tryptophan metabolism. IDO1 is expressed widely throughout the body, with especially high expression in colonic intestinal tissues. To examine the role of IDO1 in the colon, transcriptome analysis was performed in both Ido1(-/-) and Ido1(+/+) mice. Gene set enrichment analysis identified the Inflammatory Response as the most significant category modulated by the absence of IDO1. This observation prompted us to further investigate the function of IDO1 in the development of tissue inflammation. By using DSS-induced experimental colitis mice models, we found that the disease in Ido1(-/-) mice was less severe than in Ido1(+/+) mice. Pharmacological inhibition of IDO1 by L-1MT attenuated the severity of DSS-colitis as well. Transcriptome analyses revealed that pathways involving TLR and NF-kB signaling were significantly down-regulated by the absence of IDO1. Furthermore, dramatic changes in TLR and NF-kB signaling resulted in substantial changes in the expression of many inflammatory cytokines and chemokines. Numbers of inflammatory cells in colon and peripheral blood were reduced in IDO1 deficiency. These findings suggest that IDO1 plays important roles in producing inflammatory responses and modulating transcriptional networks during the development of colitis.

  5. CD3 immunohistochemical staining in diagnosis of lymphocytic colitis

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Engel, Ulla; Holck, Susanne

    2016-01-01

    Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Traditionally, MC encompasses the 2 subgroups lymphocytic colitis (LC) and collagenous colitis, but recently, an additional subgroup, MC incomplete, has been introduced. Distinguishing between the subgroups relies exclusively...

  6. Yin-Chen-Hao Tang Attenuates Severe Acute Pancreatitis in Rat: An Experimental Verification of In silico Network Target Prediction

    Science.gov (United States)

    Xiang, Hong; Wang, Guijun; Qu, Jialin; Xia, Shilin; Tao, Xufeng; Qi, Bing; Zhang, Qingkai; Shang, Dong

    2016-01-01

    Yin-Chen-Hao Tang (YCHT) is a classical Chinese medicine compound that has a long history of clinical use in China for the treatment of inflammatory diseases. However, the efficacy and mechanisms of YCHT for the treatment of severe acute pancreatitis (SAP) are not known. The current study investigated the pharmacological properties of YCHT against SAP and its underlying mechanisms. A computational prediction of potential targets of YCHT was initially established based on a network pharmacology simulation. The model suggested that YCHT attenuated SAP progress by apoptosis inducement, anti-inflammation, anti-oxidation and blood lipid regulation. These effects were validated in SAP rats. YCHT administration produced the following results: (1) significantly inhibited the secretion of pancreatic enzymes and protected pancreatic tissue; (2) obviously increased the number of in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells and induced apoptosis; (3) markedly inhibited neutrophil infiltration to the impaired pancreas and reduced the inflammatory reaction; (4) notably enhanced the activities of antioxidant enzymes and decreased the nitric oxide synthase levels; (5) significantly reduced the levels of triglycerides, total cholesterol and low-density lipoprotein and increased high-density lipoprotein; and (6) significantly up-regulated peroxisome proliferator-activated receptor-γ (PPARγ) and down-regulated nuclear factor-kappa B (NF-κB). In summary, these results demonstrated that YCHT attenuated SAP progress by inducing apoptosis, repressing inflammation, alleviating oxidative stress and regulating lipid metabolism partially via regulation of the NF-κB/PPARγ signal pathway. PMID:27790147

  7. Restoration of Akt activity by the bisperoxovanadium compound bpV(pic) attenuates hippocampal apoptosis in experimental neonatal pneumococcal meningitis.

    Science.gov (United States)

    Sury, Matthias D; Vorlet-Fawer, Lorianne; Agarinis, Claudia; Yousefi, Shida; Grandgirard, Denis; Leib, Stephen L; Christen, Stephan

    2011-01-01

    Pneumococcal meningitis causes apoptosis of developing neurons in the dentate gyrus of the hippocampus. The death of these cells is accompanied with long-term learning and memory deficits in meningitis survivors. Here, we studied the role of the PI3K/Akt (protein kinase B) survival pathway in hippocampal apoptosis in a well-characterized infant rat model of pneumococcal meningitis. Meningitis was accompanied by a significant decrease of the PI3K product phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) and of phosphorylated (i.e., activated) Akt in the hippocampus. At the cellular level, phosphorylated Akt was decreased in both the granular layer and the subgranular zone of the dentate gyrus, the region where the developing neurons undergo apoptosis. Protein levels and activity of PTEN, the major antagonist of PI3K, were unaltered by infection, suggesting that the observed decrease in PIP(3) and Akt phosphorylation is a result of decreased PI3K signaling. Treatment with the PTEN inhibitor bpV(pic) restored Akt activity and significantly attenuated hippocampal apoptosis. Co-treatment with the specific PI3K inhibitor LY294002 reversed the restoration of Akt activity and attenuation of hippocampal apoptosis, while it had no significant effect on these parameters on its own. These results indicate that the inhibitory effect of bpV(pic) on apoptosis was mediated by PI3K-dependent activation of Akt, strongly suggesting that bpV(pic) acted on PTEN. Treatment with bpV(pic) also partially inhibited the concentration of bacteria and cytokines in the CSF, but this effect was not reversed by LY294002, indicating that the effect of bpV(pic) on apoptosis was independent of its effect on CSF bacterial burden and cytokine levels. These results indicate that the PI3K/Akt pathway plays an important role in the death and survival of developing hippocampal neurons during the acute phase of pneumococcal meningitis.

  8. Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages.

    Science.gov (United States)

    Jiang, Xingwei; Yu, Jiahui; Shi, Qingzhu; Xiao, Yan; Wang, Wei; Chen, Guojiang; Zhao, Zhi; Wang, Renxi; Xiao, He; Hou, Chunmei; Feng, Jiannan; Ma, Yuanfang; Shen, Beifen; Wang, Lili; Li, Yan; Han, Gencheng

    2015-10-01

    Tim-3 is involved in the physiopathology of inflammatory bowel disease (IBD), but the underlying mechanism is unknown. Here, we demonstrated that, in mouse with DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1 macrophages, while Tim-3 downregulation or blockade resulted in an increased M1 response. Adoptive transfer of Tim-3-silenced macrophages worsened DSS colitis and enhanced inflammation, while Tim-3 overexpression attenuated DSS colitis by decreasing the M1 macrophage response. Co-culture of Tim-3-overexpressing macrophages with intestinal lymphocytes decreased the pro-inflammatory response. Tim-3 shaped intestinal macrophage polarization may be TLR-4 dependent since Tim-3 blockade failed to exacerbate colitis or increase M1 macrophage response in the TLR-4 KO model. Finally, Tim-3 signaling inhibited phosphorylation of IRF3, a TLR-4 downstream transcriptional factor regulating macrophage polarization. A better understanding of this pathway may shed new light on colitis pathogenesis and result in a new therapeutic strategy.

  9. Lessons in IBD Pathogenesis from New Animal Models of Spontaneous Colitis

    Directory of Open Access Journals (Sweden)

    R Balfour Sartor

    1995-01-01

    Full Text Available The recent explosion of transgenic and targeted gene deleted (knockout [KO] rodents has yielded a number of new animal models of spontaneous, chronic intestinal inflammation that have provided novel insights into the pathogenesis of human inflammatory bowel disease (IBD. Spontaneous colitis resulting from deletion of genes encoding key immunoregulatory cytokines (interleukin [IL]-2, IL-10 and transforming growth factor [TGF]-beta and T cell receptors (TCRs demonstrates that an intact mucosal immune response prevents colitis. The TCR KO model incriminates B lymphocytes in spontaneous colonic inflammation – TCR KO with intact B cells causes colitis, but simultaneous deletion of T and B cells does not. This model and induction of colitis in severe combined immunodeficient (SCID mice by constitution with one T cell subset (CD45RHhi, but prevention by addition of the CD45RBlo subset, strongly suggest that T cell subsets down-regulate inflammation in the normal, immunocompetent host. An essential role for normal luminal bacteria in induction and perpetuation of enterocolitis is provided by the absence of chronic intestinal inflammation in germ-free (sterile IL-2 KO mice and human leukocyte antigen (HLA-B27 transgenic rats, and attenuated inflammation in IL-2 and IL-10 KO mice raised under specific pathogen-free conditions. The fundamental role of host genetic susceptibility in chronic intestinal inflammation and systemic manifestations is established by development of spontaneous colitis and perianal inflammation in C3H/HeJ Bir substrain mice and HLA-B27 transgenic rats.

  10. Synchronous Occurrence of Collagenous and Pseudomembranous Colitis

    Directory of Open Access Journals (Sweden)

    Z Vesoulis

    2000-01-01

    Full Text Available Synchronous collagenous and pseudomembranous colitis has not been previously reported. A 73-year-old woman presented with chronic watery diarrhea and abdominal cramping of six weeks’ duration. Biopsies of the colon revealed findings of collagenous colitis involving the endoscopically normal right colon, and superimposed collagenous and pseudomembranous colitis involving the rectosigmoid colon. Endoscopically, the left colon revealed discrete ulcerative plaques, and Clostridium difficile toxin A assay was positive. The patient partially responded to a three-week regimen of metronidazole, and symptoms resolved completely with subsequent steroid therapy. At follow-up endoscopy four months later, colon biopsies demonstrated persistence of subepithelial collagen but no pseudomembranes. The patient remained asymptomatic during this interval. Collagenous colitis has been reported in association with other inflammatory bowel diseases, including lymphocytic colitis, sprue and idiopathic inflammatory bowel disease. This unique association of collagenous colitis with an endotoxigenic inflammatory bowel disease is presented with a review of related disease features.

  11. Clear cell colitis: A form of microscopic colitis in children

    Institute of Scientific and Technical Information of China (English)

    Jan J(o)zefczuk; Bogdan Marian Wozniewicz

    2008-01-01

    AIM: To describe a new clinical and pathological subtype of microscopic colitis in children.METHODS: A selected group of children with abdominal pain, constipation and/or diarrhoea showing discrete or no macroscopic abnormalities on endoscopy was described.RESULTS: Multiple biopsies of colon showed large mononuclear clear cells in lamina propria of mucous membrane provided that good quality histological sections were performed and observed under a higher magnification. Otherwise, they could be misinterpreted as artefacts. Their presence in routine histology might suggest a systemic storage disease (Whipple's disease), and neuronal intestine dysplasia.Using immunohistochemical staining and electron microscopy we confirmed their origin from CD68 positive mononuclear macrophages.CONCLUSION: The presence of large clear cells is a constant microscopic feature. Failure of transient large bowel stationary macrophages plays a role in the pathogenesis of this benign microscopic clear cell colitis,sometimes coexisting with allergy.

  12. Use of budesonide in the treatment of microscopic colitis

    Directory of Open Access Journals (Sweden)

    Tangri Vikram

    2010-01-01

    Full Text Available Collagenous colitis and lymphocytic colitis, the two types of microscopic colitis, cause watery diarrhea. Budesonide, a glucocorticoid medication with limited systemic availability, is commonly used to treat these illnesses. Budesonide has proven efficacy in the induction of clinical remission in both collagenous colitis and lymphocytic colitis. Budesonide is effective as a maintenance drug for patients with collagenous colitis, but has not been studied for this indication in patients with lymphocytic colitis. This drug improves quality of life in patients while causing few mild adverse events. Budesonide is an effective treatment of microscopic colitis that is safe and well tolerated.

  13. Microscopic Colitis: An Approach to Treatment

    Directory of Open Access Journals (Sweden)

    Nilesh Chande

    2008-01-01

    Full Text Available Microscopic colitis – including collagenous colitis and lymphocytic colitis – causes chronic watery diarrhea, usually in middle-aged or elderly patients. There is an association with celiac disease and certain medications. Medical treatment includes various antidiarrheal agents, mesalamine, corticosteroids and immunosuppressant drugs. Rarely, patients require surgery for refractory disease. An evidence-based and practical approach to treatment should optimize the treatment response while minimizing potential adverse events.

  14. Surveillance for colitis-associated colon neoplasia

    Institute of Scientific and Technical Information of China (English)

    Hugh; James; Freeman

    2010-01-01

    The risk of developing colon cancer is increased in colitis patients, particularly if the disease is extensive and its duration long-standing. Endoscopic guidelines have been developed with the goal of detecting early neoplastic changes prior to development of advanced malignancy. Unfortunately, the natural history of this superimposed neoplastic process in colitis appears to be very heterogeneous and poorly understood. Moreover, there are numerous confounding variables in colitis patients that limit accura...

  15. Highly specific blockade of CCR5 inhibits leukocyte trafficking and reduces mucosal inflammation in murine colitis.

    Science.gov (United States)

    Mencarelli, Andrea; Cipriani, Sabrina; Francisci, Daniela; Santucci, Luca; Baldelli, Franco; Distrutti, Eleonora; Fiorucci, Stefano

    2016-08-05

    Targeted disruption of leukocyte trafficking to the gut represents a promising approach for the treatment of inflammatory bowel diseases (IBDs). CCR5, the shared receptor for MIP1α and β and RANTES, is expressed by multiple leukocytes. Here, we aimed to determine the role of CCR5 in mediating leukocyte trafficking in models of colitis, and evaluate the therapeutic potential of maraviroc, an orally active CCR5 antagonist used in the treatment of CCR5-tropic HIV. Acute and chronic colitis were induced by administration of DSS or TNBS to wild-type and CCR5(-/-) mice or adoptive transfer of splenic naïve CD4(+) T-cells from wild type or CCR5(-/-) mice into RAG-1(-/-). CCR5 gene ablation reduced the mucosal recruitment and activation of CCR5-bearing CD4(+) and CD11b(+) leukocytes, resulting in profound attenuation of signs and symptoms of inflammation in the TNBS and transfer models of colitis. In the DSS/TNBS colitis and in the transfer model, maraviroc attenuated development of intestinal inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes. In summary, CCR5 regulates recruitment of blood leukocytes into the colon indicating that targeting CCR5 may offer therapeutic options in IBDs.

  16. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M

    2012-02-03

    Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

  17. Cyclooxygenase-2 immunoreactivity in collagenous colitis

    DEFF Research Database (Denmark)

    Wildt, Signe; Rumessen, Jüri J; Csillag, Claudio

    2009-01-01

    Collagenous colitis (CC) is an inflammatory bowel disease of unknown aetiology and pathogenesis. In ulcerative colitis and Crohn's disease, prostaglandins may be involved in the pathogenesis of inflammation, and increased expression of cyclo-oxygenase-2 (COX-2) has been detected. The purpose...... with samples from eight normal controls, and samples from eight patients with ulcerative colitis or Crohn's disease. Specimens from patients with CC expressed COX-2 protein in increased amounts compared with controls, but similar to patients with ulcerative colitis and Crohn's disease. COX-2 expression...

  18. Green tea polyphenol extract attenuates lung injury in experimental model of carrageenan-induced pleurisy in mice.

    Science.gov (United States)

    Di Paola, Rosanna; Mazzon, Emanuela; Muià, Carmelo; Genovese, Tiziana; Menegazzi, Marta; Zaffini, Raffaela; Suzuki, Hisanory; Cuzzocrea, Salvatore

    2005-06-29

    Here we investigate the effects of the green tea extract in an animal model of acute inflammation, carrageenan-induced pleurisy. We report here that green tea extract (given at 25 mg/kg i.p. bolus 1 h prior to carrageenan), exerts potent anti-inflammatory effects in an animal model of acute inflammation in vivo. Injection of carrageenan (2%) into the pleural cavity of mice elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained many neutrophils (PMNs), an infiltration of PMNs in lung tissues and increased production of nitrite/nitrate, tumour necrosis factor alpha. All parameters of inflammation were attenuated by green tea extract treatment. Furthermore, carrageenan induced an up-regulation of the adhesion molecule ICAM-1, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS) formation, as determined by immunohistochemical analysis of lung tissues. Staining for the ICAM-1, nitrotyrosine, and PARS was reduced by green tea extract. Our results clearly demonstrate that treatment with green tea extract exerts a protective effect and offers a novel therapeutic approach for the management of lung injury.

  19. Green tea polyphenol extract attenuates lung injury in experimental model of carrageenan-induced pleurisy in mice

    Directory of Open Access Journals (Sweden)

    Suzuki Hisanory

    2005-06-01

    Full Text Available Abstract Here we investigate the effects of the green tea extract in an animal model of acute inflammation, carrageenan-induced pleurisy. We report here that green tea extract (given at 25 mg/kg i.p. bolus 1 h prior to carrageenan, exerts potent anti-inflammatory effects in an animal model of acute inflammation in vivo. Injection of carrageenan (2% into the pleural cavity of mice elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained many neutrophils (PMNs, an infiltration of PMNs in lung tissues and increased production of nitrite/nitrate, tumour necrosis factor alpha. All parameters of inflammation were attenuated by green tea extract treatment. Furthermore, carrageenan induced an up-regulation of the adhesion molecule ICAM-1, as well as nitrotyrosine and poly (ADP-ribose synthetase (PARS formation, as determined by immunohistochemical analysis of lung tissues. Staining for the ICAM-1, nitrotyrosine, and PARS was reduced by green tea extract. Our results clearly demonstrate that treatment with green tea extract exerts a protective effect and offers a novel therapeutic approach for the management of lung injury.

  20. Lack of Platelet-Activating Factor Receptor Attenuates Experimental Food Allergy but Not Its Metabolic Alterations regarding Adipokine Levels

    Science.gov (United States)

    Batista, Nathália Vieira; Fonseca, Roberta Cristelli; Perez, Denise; Pereira, Rafaela Vaz Sousa; de Lima Alves, Juliana; Pinho, Vanessa; Faria, Ana Maria Caetano; Cara, Denise Carmona

    2016-01-01

    Platelet-activating factor (PAF) is known to be an important mediator of anaphylaxis. However, there is a lack of information in the literature about the role of PAF in food allergy. The aim of this work was to elucidate the participation of PAF during food allergy development and the consequent adipose tissue inflammation along with its alterations. Our data demonstrated that, both before oral challenge and after 7 days receiving ovalbumin (OVA) diet, OVA-sensitized mice lacking the PAF receptor (PAFR) showed a decreased level of anti-OVA IgE associated with attenuated allergic markers in comparison to wild type (WT) mice. Moreover, there was less body weight and adipose tissue loss in PAFR-deficient mice. However, some features of inflamed adipose tissue presented by sensitized PAFR-deficient and WT mice after oral challenge were similar, such as a higher rate of rolling leukocytes in this tissue and lower circulating levels of adipokines (resistin and adiponectin) in comparison to nonsensitized mice. Therefore, PAF signaling through PAFR is important for the allergic response to OVA but not for the adipokine alterations caused by this inflammatory process. Our work clarifies some effects of PAF during food allergy along with its role on the metabolic consequences of this inflammatory process. PMID:27314042

  1. The misdiagnosis of ischaemic colitis

    Energy Technology Data Exchange (ETDEWEB)

    Rudd, Joanne [Department of Radiology, West Suffolk Hospital, Hardwick Lane, Bury St Edmunds, Suffolk IP33 2QZ (United Kingdom)]. E-mail: joanne.rudd@wsh.nhs.uk

    2006-11-15

    This case study followed the pathway taken by an elderly patient who presented as an emergency with rectal bleeding. Views obtained of the colon by flexible sigmoidoscopy suggested an initial diagnosis of colorectal carcinoma but this proved to be incorrect. It was a combination of the histology obtained from the initial and subsequent endoscopies, barium enema and the clinical history that finally gave rise to the correct diagnosis of ischaemic colitis. Opinion is currently divided as to whether sigmoidoscopy or colonoscopy is the most appropriate test for those patients presenting with rectal bleeding. Ischaemic colitis is a disease that can present with many differing symptoms depending on the degree of severity of the ischaemia.

  2. Nerol alleviates pathologic markers in the oxazolone-induced colitis model.

    Science.gov (United States)

    González-Ramírez, Adriana Estrella; González-Trujano, María Eva; Orozco-Suárez, Sandra A; Alvarado-Vásquez, Noé; López-Muñoz, Francisco Javier

    2016-04-05

    Nerol is a natural monoterpene with antinociceptive and anti-inflammatory properties. Its possible beneficial effects in ulcerative colitis and its corresponding mechanism of action have not been determined to date. The aim of this study was to investigate whether nerol prevents the appearance of pathological markers and hyperalgesia in oxazolone-induced colitis, and protects against gastric damage produced by ethanol. The experimental design included groups of oxazolone-treated mice receiving nerol at 10-300 mg/kg, p.o., or a reference drug (sulfasalazine, 100 mg/kg, p.o.) compared to sham and untreated groups. Gastric damage was evaluated in the absolute ethanol-induced ulcer model in rats. Variables measured in animals with oxazolone-induced colitis included weight loss, stool consistency and macroscopic colon damage; mechanical nociception was determined by the use of von Frey filaments, whereas levels of inflammatory cytokines were assessed by enzyme-linked immunosorbent assay. Nerol (30-300 mg/kg, p.o.) prevented or significantly decreased the pathological alterations observed in the oxazolone- induced colitis model. It also showed antinociceptive effects and reduced the increased levels of inflammatory cytokines (IL-13 and TNF-α). Gastric damage was also prevented starting at 10 mg/kg, p.o. In conclusion, our results provide evidence for a beneficial effect of nerol after colitis induction involving tissue protection, antinociception and modulation of the immunological system, suggesting the therapeutic potential of this monoterpene as a novel alternative in controlling ulcerative colitis.

  3. Ulcerative colitis after Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Mohammad Aminianfar

    2014-06-01

    Full Text Available A 21 years old man has been complained of bloody diarrhea, liquid stool containing blood, pus, and fecal matter and crampy abdominal pain from four monthes ago. Ulcerative colitis relies upon the patient's history, clinical symptoms, sigmoidoscopic appearance and histology of colonic biopsy specimens. Treatment of patient started with high dose dexamethasone and prednisolone, asacole, suppository, metronidazole. Patient’s condition not improved and patient admitted in hospital. High dose prednisolone, azathioprine, sulfasalazine and folic acid were given.

  4. Current treatment of ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Johannes Meier; Andreas Sturm

    2011-01-01

    Ulcerative colitis (UC) is a chronic disease featuring recurrent inflammation of the colonic mucosa. The goal of medical treatment is to rapidly induce a steroid-free remission while at the same time preventing complications of the disease itself and its treatment. The choice of treatment depends on severity, localization and the course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) compounds is used. More extensive or severe disease should be treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Patients who do not respond to this treatment require hospitalization. Intravenous steroids or, when refractory, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-α antibodies (infliximab) or immunomodulators (azathioprine, 6-mercaptopurine) are then called for. Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding. Close collaboration between gastroenterologist and surgeon is mandatory in order not to delay surgical therapy when needed. This article is intended to give a general, practice- orientated overview of the key issues in ulcerative colitis treatment. Recommendations are based on published consensus guidelines derived from national and international guidelines on the treatment of ulcerative colitis.

  5. Current treatment of ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    JohannesMeier; AndreasSturm

    2011-01-01

    Ulcerative colitis (UC) is a chronic disease featuring re- current inflammation of the colonic mucosa. The goal of medical treatment is to rapidly induce a steroid-free remission while at the same time preventing complica- tions of the disease itself and its treatment. The choice of treatment depends on severity, localization and the course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) compounds is used. More extensive or severe disease should be treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Patients who do not respond to this treatment require hospitalization. Intravenous steroids or, when refractory, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-α antibodies (infliximab) or immunomodulators (azathioprine, 6-mercaptopurine) are then called for. Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding. Close collaboration between gastroenterologist and surgeon is mandatory in order not to delay surgical therapy when needed. This article is intended to give a general, practice-orientated overview of the key issues in ulcerative colitis treatment. Recommendations are based on published consensus guidelines derived from national and international guidelines on the treatment of ulcerative colitis.

  6. Evolution of microscopic colitis to giant cell colitis without significant intraepithelial lymphocytosis or thickened collagen plate.

    Science.gov (United States)

    De Petris, Giovanni; Chen, Longwen

    2015-05-01

    Microscopic colitis (MC) is an umbrella term that encompasses lymphocytic colitis (LC) and collagenous colitis (CC). Several histological variants of these 2 entities exist; among them is the uncommon giant cell colitis (GCC), in which histiocytic giant cells (GCs) are present in background of CC or LC. We report the case of a 71-year-old woman complaining of watery diarrhea for several years that was diagnosed with CC. At follow-up, she developed giant cell colitis (GCC). Nine years later, a colectomy revealed a form of microscopic colitis in which significant intraepithelial lymphocytosis and collagen plate thickening have disappeared while GCs persisted with diffuse mononuclear cells inflammation of the lamina propria. Thinning of the collagen plate in association with GCs has been described previously. The case contributes the possibility of further evolution of MC into a pure giant cell colitis in which the prototypical manifestations of MC have all but disappeared.

  7. An analytical and experimental study of sound propagation and attenuation in variable-area ducts. [reducing aircraft engine noise

    Science.gov (United States)

    Nayfeh, A. H.; Kaiser, J. E.; Marshall, R. L.; Hurst, L. J.

    1978-01-01

    The performance of sound suppression techniques in ducts that produce refraction effects due to axial velocity gradients was evaluated. A computer code based on the method of multiple scales was used to calculate the influence of axial variations due to slow changes in the cross-sectional area as well as transverse gradients due to the wall boundary layers. An attempt was made to verify the analytical model through direct comparison of experimental and computational results and the analytical determination of the influence of axial gradients on optimum liner properties. However, the analytical studies were unable to examine the influence of non-parallel ducts on the optimum linear conditions. For liner properties not close to optimum, the analytical predictions and the experimental measurements were compared. The circumferential variations of pressure amplitudes and phases at several axial positions were examined in straight and variable-area ducts, hard-wall and lined sections with and without a mean flow. Reasonable agreement between the theoretical and experimental results was obtained.

  8. Effect of COX-2 inhibitor after TNBS-induced colitis in Wistar rats.

    Science.gov (United States)

    Paiotti, Ana Paula Ribeiro; Miszputen, Sender Jankiel; Oshima, Celina Tizuko Fujiyama; de Oliveira Costa, Henrique; Ribeiro, Daniel Araki; Franco, Marcello

    2009-08-01

    Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. Some studies suggest that antiinflammatory drugs are a promising alternative for treatment of the disease. Thus, this study aimed to evaluate the effect of lumiracoxib, a selective-cyclooxygenase-2 (COX-2) inhibitor, on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. Wistar rats (n = 25) were randomized into four groups, as follows: Group (1) Sham group: sham induced-colitis rats; Group (2) TNBS group: nontreated induced-colitis rats; Group (3) Lumiracoxib control group; and Group (4) Lumiracoxib-treated induced-colitis rats. Our results showed that rats from groups 2 and 4 presented similar histopathological damage and macroscopic injury in the distal colon as depicted by significant statistically differences (P TNBS-induced experimental colitis. Thus, the use of COX-2 inhibitors for treating IBD should be considered with caution and warrants further experimental investigation to elucidate their applicability.

  9. Si Shen Wan Regulates Phospholipase Cγ-1 and PI3K/Akt Signal in Colonic Mucosa from Rats with Colitis

    Directory of Open Access Journals (Sweden)

    Duan-yong Liu

    2015-01-01

    Full Text Available The present study explored the feasible pathway of Si Shen Wan (SSW in inhibiting apoptosis of intestinal epithelial cells (IECs by observing activation of phospholipase Cγ-1 (PLC-γ1 and PI3K/Akt signal in colonic mucosa from rats with colitis. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS in the Sprague-Dawley rats. After SSW was administrated for 7 days after TNBS infusion, western blot showed an increment in levels of PI3K, p-Akt, and IL-23 and a decrement in levels of PLC-γ1 and HSP70 in colonic mucosal injury induced by TNBS. Meanwhile, assessments by ELISA revealed an increment in concentrations of IL-2, IL-6, and IL-17 and a reduction in level of TGF-β after TNBS challenge. Impressively, treatment with SSW for 7 days significantly attenuated the expressions of PI3K and p-Akt and the secretion of IL-2, IL-6, IL-17, and IL-23 and promoted the activation of PLC-γ1, HSP70, and TGF-β. Our previous studies had demonstrated that SSW restored colonic mucosal ulcers by inhibiting apoptosis of IECs. The present study demonstrated that the effect of SSW on inhibiting apoptosis of IECs was realized probably by activation of PLC-γ1 and suppression of PI3K/Akt signal pathway.

  10. Recombinant human MFG-E8 ameliorates colon damage in DSS- and TNBS-induced colitis in mice.

    Science.gov (United States)

    Zhang, Yinzhong; Brenner, Max; Yang, Weng-Lang; Wang, Ping

    2015-05-01

    Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the digestive system and typically requires lifelong medical care. Recombinant human MFG-E8 (rhMFG-E8) is a 364-amino acid protein, which promotes apoptotic cell clearance and reduces inflammation. This study investigates the therapeutic effect of rhMFG-E8 on two well-established mouse models of IBD. Acute mucosal injury leading to colitis was caused by exposing C57BL/6 mice to 4% dextran sodium sulfate (DSS) in the drinking water over 7 days, and BALB/c mice to a single intrarectal dose of 2.75 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Upon clinical onset of colitis (day 2 in the DSS model and day 1 in the TNBS model), mice were treated with daily subcutaneous injections of rhMFG-E8 (60 or 120 μg/kg/day) or vehicle (saline) for 6 days. Treatment with rhMFG-E8 significantly attenuated colitis in both models in a dose-dependent way. Treatment of DSS-induced colitis with rhMFG-E8 (120 μg/kg/day) decreased weight loss by 59%, the colitis severity score by 71%, and colon shrinkage by 49% when compared with vehicle. Similarly, treatment of TNBS-induced colitis with rhMFG-E8 (120 μg/kg/day) decreased weight loss by 97%, the colitis severity score by 82%, and colon shrinkage by 62% when compared with vehicle. In both models, the colons of animals receiving rhMFG-E8 showed marked reduction in neutrophil infiltration, cytokine and chemokine expression, and apoptotic cell counts. In conclusion, rhMFG-E8 ameliorates DSS- and TNBS-induced colitis, suggesting that it has the potential to become a novel therapeutic agent for IBD.

  11. Crohn's Disease and Ulcerative Colitis: Emotional Factors

    Science.gov (United States)

    ... IS THE CAUSE OF ULCERATIVE COLITIS AND CROHN’S DISEASE? The origin of IBD is still unknown. It is possible that a combination of factors may be the underlying cause of Crohn’s disease and ulcerative colitis. Researchers theorize that IBD patients ...

  12. Microscopic colitis : an unfamiliar but treatable disease

    NARCIS (Netherlands)

    van der Wouden, E J; Karrenbeld, A; Kleibeuker, J H; Dijkstra, Gerard

    2009-01-01

    Chronic diarrhoea is a frequent complaint in clinical practice. Microscopic colitis is the cause of this symptom in 10% of these cases and the prevalence is rising. To exclude microscopic colitis a colonoscopy with multiple biopsies of different regions of the colon is mandatory. A sigmoidoscopy alo

  13. Kalium kanalers rolle i inflammation i Colitis Ulcerosa

    DEFF Research Database (Denmark)

    Hansen, Lars Koch

    2011-01-01

    Gennemgang af T-cellers kalium kanaler og deres mulige rolle i Colitis Ulcerosa. Artiklen skrevet til Den danske Colitis-Crohn Forenings Medlemsblad.......Gennemgang af T-cellers kalium kanaler og deres mulige rolle i Colitis Ulcerosa. Artiklen skrevet til Den danske Colitis-Crohn Forenings Medlemsblad....

  14. Changes of CD8+CD28- T regulatory cells in rat model of colitis induced by 2,4-dinitrofluorobenzene

    Institute of Scientific and Technical Information of China (English)

    Wen-Bin Xiao; Yu-Lan Liu

    2003-01-01

    AIM: To determine the changes of CD8+ T subsets especially CD8+CD28- T regulatory cells in rat model of experimental colitis induced by 2,4-dinitrofiuorobenzene (DNFB).METHODS: The rat model of experimental colitis was induced by enema with DNFB. Ten days later, colonic intraepithelial and splenic lymphocytes were isolated from colitis animals (n=16) and controls (n=8). The proportion of CD8+ T cells, CD8+CD28+ T cells and CD8+CD28- T regulatory cells were determined by flow cytometry.RESULTS: The model of experimental colitis was successfully established by DNFB that was demonstrated by bloody diarrhea, weight loss and colonic histopathology. The proportion of CD8+ T cells in either splenic or colonic intraepithelial lymphocytes was not significantly different between colitis animals and controls (spleen: 34.6±7.24 % vs33.5±9.41%,colon: 14.0±8.93 % vs 18.0±4.06 %, P>0.05). But CD8+CD28-T regulatory cells from colitis animals were significantly more than those from controls (spleen: 11.3±2.26 % vs5.64±1.01%,colon: 6.50±5.37 % vs 1.07±0.65 %, P<0.05). In contrast,CD8+CD28+ T cells from colitis animals were less than those from controls (spleen: 23.3±6.14 % vs27.8±9.70 %, P=0.06;colon: 7.52±4.18 % vs 16.9±4.07 %, P<0.05). The proportion of CD8+CD28- T regulatory cells in splenic and colonintraepithelial CD8+ T cells from colitis animals was higher than that from controls (spleen: 33.3±5.49 % vs 18.4±7.26 %,colon: 46.0±14.3 % vs6.10±3.72 %, P<0.005).CONCLUSION: Experimental colitis of rats can be induced by DNFB with simplicity and good reproducibility. The proportion of CD8+CD28- T regulatory cells in rats with experimental colitis is increased, which may be associated with the pathogenesis of colitis.

  15. Altered sympathovagal balance and pain hypersensitivity in TNBS-induced colitis

    Science.gov (United States)

    Furgała, Agata; Dobrek, Łukasz; Juszczak, Kajetan; Thor, Piotr

    2016-01-01

    Introduction Pain hypersensitivity, abnormal motility and autonomic dysfunction contribute to functional symptoms of inflammatory bowel disease (IBD). Material and methods The aim of this study was to assess: nociceptive thresholds for mechanical allodynia (MA) and thermal hyperalgesia (TH), intestinal motility (distal colonic transit and emptying), and cardiac autonomic neuropathy (indices of heart rate variability – HRV) in male Wistar rats with experimental trinitrobenzene sulfonic acid (TNBS) induced colitis. To identify a potential vagal contribution the bilateral subdiaphragmatic vagotomy (SDV) was performed. Results Experimental colitis resulted in a significant decrease in pain threshold (MA 23.60 ±2.12, p rats with colitis showed the strongest nociceptive response (MA 22.46 ±3.02, p induces excessive hyperalgesia. PMID:28144278

  16. Lactobacillus acidophilus ATCC 4356 inhibits biofilm formation by C. albicans and attenuates the experimental candidiasis in Galleria mellonella.

    Science.gov (United States)

    Vilela, Simone F G; Barbosa, Júnia O; Rossoni, Rodnei D; Santos, Jéssica D; Prata, Marcia C A; Anbinder, Ana Lia; Jorge, Antonio O C; Junqueira, Juliana C

    2015-01-01

    Probiotic strains of Lactobacillus have been studied for their inhibitory effects on Candida albicans. However, few studies have investigated the effect of these strains on biofilm formation, filamentation and C. albicans infection. The objective of this study was to evaluate the influence of Lactobacillus acidophilus ATCC 4356 on C. albicans ATCC 18804 using in vitro and in vivo models. In vitro analysis evaluated the effects of L. acidophilus on the biofilm formation and on the capacity of C. albicans filamentation. For in vivo study, Galleria mellonella was used as an infection model to evaluate the effects of L. acidophilus on candidiasis by survival analysis, quantification of C. albicans CFU/mL, and histological analysis. The direct effects of L. acidophilus cells on C. albicans, as well as the indirect effects using only a Lactobacillus culture filtrate, were evaluated in both tests. The in vitro results showed that both L. acidophilus cells and filtrate were able to inhibit C. albicans biofilm formation and filamentation. In the in vivo study, injection of L. acidophilus into G. mellonella larvae infected with C. albicans increased the survival of these animals. Furthermore, the number of C. albicans CFU/mL recovered from the larval hemolymph was lower in the group inoculated with L. acidophilus compared to the control group. In conclusion, L. acidophilus ATCC 4356 inhibited in vitro biofilm formation by C. albicans and protected G. mellonella against experimental candidiasis in vivo.

  17. Inhibition of p38 mitogen-activated protein kinase attenuates experimental autoimmune hepatitis: Involvement of nuclear factor kappa B

    Institute of Scientific and Technical Information of China (English)

    Xiong Ma; Yi-Tao Jia; De-Kai Qiu

    2007-01-01

    AIM: To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) in murine experimental autoimmune hepatitis (EAH).METHODS: To induce EAH, the syngeneic S-100 antigen emulsified in complete Freud's adjuvant was injected intraperitoneally into adult male C57BI/6 mice. Liver injury was assessed by serum ALT and liver histology.The expression and activity of p38 MAPK were measured by Western blot and kinase activity assays. In addition,DNA binding activities of nuclear factor kappa B (NF-κB)were analyzed by electrophoretic mobility shift assay. The effects of SB203580, a specific p38 MAPK inhibitor, on liver injuries and expression of proinflammatory cytokines (interferon-γ, IL-12, IL-1β and TNF-α) were observed.RESULTS: The activity of p38 MAPK and NF-κB was increased and reached its peak 14 or 21 d after the first syngeneic S-100 administration. Inhibition of p38 MAPK activation by SB203580 decreased the activation of NF-κB and the expression of proinflammatory cytokines.Moreover, hepatic injuries were improved significantly after SB203580 administration.CONCLUSION: p38 MAPK and NF-κB play an important role in an animal model of autoimmune hepatitis (AIH)induced by autoantigens.

  18. Lactobacillus acidophilus ATCC 4356 inhibits biofilm formation by C. albicans and attenuates the experimental candidiasis in Galleria mellonella

    Science.gov (United States)

    Vilela, Simone FG; Barbosa, Júnia O; Rossoni, Rodnei D; Santos, Jéssica D; Prata, Marcia CA; Anbinder, Ana Lia; Jorge, Antonio OC; Junqueira, Juliana C

    2015-01-01

    Probiotic strains of Lactobacillus have been studied for their inhibitory effects on Candida albicans. However, few studies have investigated the effect of these strains on biofilm formation, filamentation and C. albicans infection. The objective of this study was to evaluate the influence of Lactobacillus acidophilus ATCC 4356 on C. albicans ATCC 18804 using in vitro and in vivo models. In vitro analysis evaluated the effects of L. acidophilus on the biofilm formation and on the capacity of C. albicans filamentation. For in vivo study, Galleria mellonella was used as an infection model to evaluate the effects of L. acidophilus on candidiasis by survival analysis, quantification of C. albicans CFU/mL, and histological analysis. The direct effects of L. acidophilus cells on C. albicans, as well as the indirect effects using only a Lactobacillus culture filtrate, were evaluated in both tests. The in vitro results showed that both L. acidophilus cells and filtrate were able to inhibit C. albicans biofilm formation and filamentation. In the in vivo study, injection of L. acidophilus into G. mellonella larvae infected with C. albicans increased the survival of these animals. Furthermore, the number of C. albicans CFU/mL recovered from the larval hemolymph was lower in the group inoculated with L. acidophilus compared to the control group. In conclusion, L. acidophilus ATCC 4356 inhibited in vitro biofilm formation by C. albicans and protected G. mellonella against experimental candidiasis in vivo. PMID:25654408

  19. Microscopic colitis: A review of etiology, treatment and refractory disease

    OpenAIRE

    Park, Tina; Cave, David; Marshall, Christopher

    2015-01-01

    Microscopic colitis is a common cause of chronic, nonbloody diarrhea. Microscopic colitis is more common in women than men and usually affects patients in their sixth and seventh decade. This article reviews the etiology and medical management of microscopic colitis. The etiology of microscopic colitis is unknown, but it is associated with autoimmune disorders, such as celiac disease, polyarthritis, and thyroid disorders. Smoking has been identified as a risk factor of microscopic colitis. Ex...

  20. Probiotic therapy using live combined bifidobacterium, lactobacillus and enterococcus for experimental colitis in rats model%微生态制剂对实验性大鼠结肠炎的治疗

    Institute of Scientific and Technical Information of China (English)

    万岳梦; 朱尤庆; 夏冰; 罗峻

    2010-01-01

    Objective To evaluate the effect of live combined bifidobacterium, lactobacillus and enterococcus capsules for colitis in rats induced by trinitrobenzenesulfonic acid (TNBS), so as to explore a new therapy for inflammatory bowel diseases (IBD). Methods 50 female adult Sprague-Dawley rats were randomly divided into 5 groups i. e. normal control group(G1) ,untreated TNBS-induced colitis(G2) ,TNBS-induced colitis treated with live combined bifidobacterium, lactobacillus and enterococcus (G3), TNBS-induced colitis treated with olsalazine (G4) and TNBS-induced colitis treated with both live combined bifidobacterium, lactobacillus and enterococcus and olsalazine at the same dose and duration (G5). Each group received its respective treatment. Serum levels of C-reactive protein (CRP), TNFα and IL-10 were measured with ELISA, colonic myeloperoxidase (MPO) activity was determined with spectrophotometric method, histopathologic picture of the colon of each rat was studied with microscope and colonic mucosa damage index(CMDI) was recorded. Results Serum CRP,TNFα,IL-10,CMDI and colonic MPO in G1 were significantly lower than those in G2 (P < 0. 001) with normal colonic architecture. G2 exhibited the most severe colonic inflammation and the highest levels of CRP,TNFα, IL-10, CMDI and colonic MPO with stastical significance. Treatment groups G3, G4 and G5 showed more obvious colonic inflammatory remission and lower levels of serum CRP,TNFα , IL-10 and colonic MPO, G5 being most notable when compared to G2 with stastical significance. In G2, serum levels of CRP, TNFα, IL-10 and colonic MPO activity each correlated positively with CMDI (P < 0. 001). Conclusions Live combined bifidobacterium, lactobacillus and enterococcus can effectively ameliorate colitis in rats induced by TNBS; the underlying mechanism may possibly be associated with the serum levels of cytokines.%目的 评价微生态制剂双歧三联活菌对三硝基苯磺酸钠(TNBS)诱导的大鼠结肠炎的疗

  1. Sulphasalazine-Induced Pseudomembranous Colitis

    Directory of Open Access Journals (Sweden)

    Hugh J Freeman

    1991-01-01

    Full Text Available An 18-year-old female with ankylosing spondylitis developed fever, abdominal pain and diarrhea on two occasions after starting sulphasalazine therapy. Flexible sigmoidoscopy revealed pseudomembranous colitis; fecal cultures were positive for Clostridium difficile; and C difficile toxin assay was positive. Despite the frequent use of sulphasalazine in the management of inflammatory bowel disease, this complication has been apparently rare. Clinicians should be wary of the onset of diarrhea in patients receiving sulphasalazine, whether for inflammatory bowel disease or other conditions.

  2. Rifampin-associated pseudomembranous colitis.

    Science.gov (United States)

    Chen, Tun-Chieh; Lu, Po-Liang; Lin, Wei-Ru; Lin, Chun-Yu; Wu, Jeng-Yih; Chen, Yen-Hsu

    2009-08-01

    Pseudomembranous colitis (PMC) is known to develop after antibiotic treatment, but is rarely associated with antituberculosis (anti-TB) agents. We report a 28-year-old woman without underlying diseases developing PMC after 126 days of anti-TB treatment. Severe diarrhea and abdominal cramping pain were experienced. Colonoscopic biopsy proved the diagnosis of PMC. Her symptoms improved after discontinuing the anti-TB agents but recurred shortly after challenging with rifampin and isoniazid. Metronidazole administration and replacement of rifampin with levofloxacin successfully cured the PMC. Our report supports the notion that rifampin can induce PMC.

  3. Status of colitis-associated cancer in ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Tetsushi Kinugasa; Yoshito Akagi

    2016-01-01

    Surgical therapy for ulcerative colitis(UC) depends on the medical therapy administered for the patient’s condition. UC is a benign disease. However, it has been reported that the rare cases of cancer in UC patients are increasing, and such cases have a worse prognosis. Recently, surgical therapy has greatly changed, there has been quite an increase in the number of UC patients with high-grade dysplasia and/or cancer. These lesions are known as colitis-associated cancer(CAC). The relationship between inflammation and tumorigenesis is well-established, and in the last decade, a great deal of supporting evidence has been obtained from genetic, pharmacological, and epidemiological studies. Inflammatory bowel disease, especially UC, is an important risk factor for the development of colon cancer. We should determine the risk factors for UC patients with cancer based on a large body of data, and we should attempt to prevent the increase in the number of such patients using these newly identified risk factors in the near future. Actively introducing the surgical treatment in addition to medical treatment should be considered. Several physicians should analyze UC from their unique perspectives in order to establish new clinically relevant diagnostic and treatment methods in the future. This article discusses CAC, including its etiology, mechanism, diagnosis, and treatment in UC patients.

  4. Deficiency of tenascin-C and attenuation of blood-brain barrier disruption following experimental subarachnoid hemorrhage in mice.

    Science.gov (United States)

    Fujimoto, Masashi; Shiba, Masato; Kawakita, Fumihiro; Liu, Lei; Shimojo, Naoshi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Suzuki, Hidenori

    2016-06-01

    OBJECT Tenascin-C (TNC), a matricellular protein, is induced in the brain following subarachnoid hemorrhage (SAH). The authors investigated if TNC causes brain edema and blood-brain barrier (BBB) disruption following experimental SAH. METHODS C57BL/6 wild-type (WT) or TNC knockout (TNKO) mice were subjected to SAH by endovascular puncture. Ninety-seven mice were randomly allocated to WT sham-operated (n = 16), TNKO sham-operated (n = 16), WT SAH (n = 34), and TNKO SAH (n = 31) groups. Mice were examined by means of neuroscore and brain water content 24-48 hours post-SAH; and Evans blue dye extravasation and Western blotting of TNC, matrix metalloproteinase (MMP)-9, and zona occludens (ZO)-1 at 24 hours post-SAH. As a separate study, 16 mice were randomized to WT sham-operated, TNKO sham-operated, WT SAH, and TNKO SAH groups (n = 4 in each group), and activation of mitogen-activated protein kinases (MAPKs) was immunohistochemically evaluated at 24 hours post-SAH. Moreover, 40 TNKO mice randomly received an intracerebroventricular injection of TNC or phosphate-buffered saline, and effects of exogenous TNC on brain edema and BBB disruption following SAH were studied. RESULTS Deficiency of endogenous TNC prevented neurological impairments, brain edema formation, and BBB disruption following SAH; it was also associated with the inhibition of both MMP-9 induction and ZO-1 degradation. Endogenous TNC deficiency also inhibited post-SAH MAPK activation in brain capillary endothelial cells. Exogenous TNC treatment abolished the neuroprotective effects shown in TNKO mice with SAH. CONCLUSIONS Tenascin-C may be an important mediator in the development of brain edema and BBB disruption following SAH, mechanisms for which may involve MAPK-mediated MMP-9 induction and ZO-1 degradation. TNC could be a molecular target against which to develop new therapies for SAH-induced brain injuries.

  5. Ultrasonic attenuation in pearlitic steel.

    Science.gov (United States)

    Du, Hualong; Turner, Joseph A

    2014-03-01

    Expressions for the attenuation coefficients of longitudinal and transverse ultrasonic waves are developed for steel with pearlitic microstructure. This type of lamellar duplex microstructure influences attenuation because of the lamellar spacing. In addition, longitudinal attenuation measurements were conducted using an unfocused transducer with 10 MHz central frequency on the cross section of a quenched railroad wheel sample. The dependence of longitudinal attenuation on the pearlite microstructure is observed from the changes of longitudinal attenuation from the quenched tread surface to deeper locations. The results show that the attenuation value is lowest and relatively constant within the quench depth, then increases linearly. The experimental results demonstrate a reasonable agreement with results from the theoretical model. Ultrasonic attenuation provides an important non-destructive method to evaluate duplex microstructure within grains which can be implemented for quality control in conjunction with other manufacturing processes.

  6. Low bone mass in microscopic colitis

    Directory of Open Access Journals (Sweden)

    Lakatos Péter

    2011-05-01

    Full Text Available Abstract Background Microscopic colitis presents with similar symptoms to classic inflammatory bowel diseases. Osteoporosis is a common complication of Crohn's disease but there are no data concerning bone metabolism in microscopic colitis. Aims The aim of the present study was to evaluate bone density and metabolism in patients with microscopic colitis. Methods Fourteen patients microscopic colitis were included in the study, and 28 healthy persons and 28 age and gender matched Crohn's disease patients were enrolled as controls. Bone mineral density was measured using dual x-ray absorptiometry at the lumbar spine, femoral neck and the radius. Serum bone formation and bone resorption markers (osteocalcin and beta-crosslaps, respectively were measured using immunoassays. Results Low bone mass was measured in 57.14% patients with microscopic colitis. Bone mineral density at the femoral neck in patients suffering from microscopic colitis and Crohn's disease was lower than in healthy controls (0.852 ± 0.165 and 0.807 ± 0.136 vs. 1.056 ± 0.126 g/cm2; p 2; p 2. Mean beta-crosslaps concentration was higher in microscopic colitis and Crohn's disease patients than controls (417.714 ± 250.37 and 466.071 ± 249.96 vs. 264.75 ± 138.65 pg/ml; p Conclusions Low bone mass is frequent in microscopic colitis, and alterations to bone metabolism are similar to those present in Crohn's disease. Therefore, microscopic colitis-associated osteopenia could be a significant problem in such patients.

  7. CT pseudomembranous colitis. Computertomographie bei pseudomembranoeser Kolitis

    Energy Technology Data Exchange (ETDEWEB)

    Gaa, J. (Heidelberg Univ., Klinikum Mannheim, Inst. fuer Klinische Radiologie (Germany)); Lee, M.J. (Massachusetts General Hospital, Boston, MA (United States). Dept. of Gastrointestinal Radiology); Georgi, M. (Heidelberg Univ., Klinikum Mannheim, Inst. fuer Klinische Radiologie (Germany))

    1993-09-01

    Pseudomembranous colitis (PMC) is an infectious colitis usually occurring as a complication of antibiotic therapy. The computed tomography (CT) findings of 10 patients with PMC are reviewed. All patients demonstrated an abnormal large bowel wall with an average thickness of 13 mm (range 7-31 mm). Additional, but less frequent findings included mesenteric inflammation, ascites, pleural effusions, and dilatation of the large or small bowel. Pancolonic involvement was seen in 7 cases, while three patients had focal colitis. Although the CT appearance of PMC is not specific, the diagnosis may be suggested in the proper clinical setting. (orig.)

  8. Pseudomembranous colitis in a pregnant woman.

    Science.gov (United States)

    Mridula, T; Pai, R R; Mathai, A M; Tantry, B V; Adhikari, P

    2010-01-01

    Pseudomembranous colitis in association with pregnancy has not been well described in English literature. Recent studies show a drastic increase in the incidence and severity of Pseudomembranous colitis in pregnant women, who were once thought to be at low risk. We report here a case of Pseudomembranous colitis in a young healthy immunocompetent pregnant lady. An early suspicion of this entity with the characteristic appearance of pseudomembranes on colonoscopy and histology confirmed the diagnosis enabling prompt treatment and complete recovery without any serious consequences.

  9. Cytomegalovirus-colitis hos immunkompetent ung mand

    DEFF Research Database (Denmark)

    Rasmussen, Eva; Grønbaek, Karin; Linnemann, Dorte

    2009-01-01

    haematochezia remained present after six months. Development of IBD subsequent to CMV colitis has previously been described, and is now suspected in our patient. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients with fever, elevated liver enzymes and bloody stools......A healthy young man was hospitalized due to fever, malaise and bloody stools for three weeks. The patient had a primary CMV infection based on biochemical, serological and ultrasonic results, and a colonoscopy was consistent with left-sided CMV colitis. He recovered spontaneously, though...

  10. Intravenous administration of mesenchymal stem cells overexpressing CXCR4 protects against experimental colitis in rats%过表达CXCR4的间充质干细胞缓解实验性结肠炎

    Institute of Scientific and Technical Information of China (English)

    刘星星; 范恒; 唐庆; 寿折星; 陶玲; 张丽娟; 左冬梅

    2016-01-01

    目的:观察过表达CXCR4的骨髓间充质干细胞治疗2,4,6-三硝基苯磺酸诱导的实验性结肠炎的效果及其潜在的免疫作用机制.方法:从♀SD大鼠骨髓中分离骨髓间充质干细胞(bone mesenchymal stem cells,BMSCs)并使用流式细胞术鉴定.通过慢病毒技术使BMSCs表达GFP(green fluorescent protein-GFP,Ad-GFP-BMSCs)或共表达CXCR4和GFP(Ad-CXCR4-BMSCs),32只大鼠被随机分成4组(n=8):空白组、模型组、Ad-GFP-BMSCs组、Ad-CXCR4-BMSCs组.采用TNBS诱导实验性结肠炎,尾静脉注射Ad-CXCR4-BMSCs或Ad-GFP-BMSCs.治疗1 wk,收集结肠组织进行HE染色和病理学分析.PCR检测结肠部位干扰素-γ(interferon-γ,IFN-γ)、肿瘤坏死因子-α(tumor necrosis factor α,TNF-α)、白介素(interleukin,IL)-6和IL-10的mRNA表达,Western blot检测信号传导子及转录激活子(signal transducer and activator of transcription,STAT)-3和磷酸化STAT-3蛋白表达,免疫组织化学检测磷酸化STAT3蛋白表达.结果:相对于空白组,模型组结肠部位的IFN-γ、TNF-α、IL-6和IL-10的mRNA表达显著上升,S TAT-3及磷酸化STAT-3的蛋白表达明显上升(P<0.05).系统治疗1 wk后,相对于模型组,Ad-GFP-BMSCs组大鼠的临床症状及结肠病理损害并没有得到有效的缓解.相对于Ad-GFP-BMSCs组,Ad-CXCR4-BMSCs组大鼠结肠组织的IFN-γ、TNF-α、IL-6的mRNA表达显著下降,IL-10 的mRNA表达显著上升(P<0.05);STAT3 及磷酸化STAT-3的蛋白表达显著下降(P<0.05).结论:过表达CXCR4的BMSCs可能通过抗炎及免疫调节机制来缓解实验性结肠炎,这可能为BMSC缓解IBD提供可靠的理论依据.%AIM:To investigate the role of SDF-1α/CXCR4 axis in the therapeutic effects of lentivirus-preconditioned bone mesenchymal stem cells (BMSCs) for 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.METHODS:BMSCs were isolated from Sprague-Dawley (SD) rats and identified by flow cytometry.Lentivirus transfection was applied to

  11. Role of C16, angiopoietin-1 and regeneration gene protein 2 in attenuating inflammation in an experimental rat model of autoimmune encephalomyelitis.

    Science.gov (United States)

    Tian, Ke-Wei; Zhang, Fan; Jiang, Hong; Wang, Beibei; Han, Shu

    2017-01-01

    Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (CNS), and results in CNS inflammation and damage to myelin. In this study, we examined the possible synergistic effects of C16, angiopoietin-1 (Ang-1) and regeneration gene protein 2 (Reg-2) in alleviating inflammation in an acute experimental autoimmune encephalomyelitis (EAE) model. We employed multiple histological, morphological and iconographic assays to examine the effect of those drugs on disease onset, clinical scores and behavioral deficits. Our results demonstrated that triple combination therapy was more efficient than the monotherapy in EAE treatment. The triple therapy significantly delayed the onset of motor symptoms, reduced disease severity, attenuated inflammatory cell infiltration and suppressed the secretion of proinflammatory cytokines. Additionally, treatment increased anti-inflammatory cytokines expression, inhibited reactive astrocytes proliferation, reduced demyelination and axonal loss, and finally reduced the neural death. Specifically, Reg-2 administration rescued oligodendrocytes and neuronal axons mainly by direct neurotrophic effects, while C16+Ang-1 (C+A) mainly improved the inflammatory milieu. In conclusion, our study suggests a possible synergistic effect through targeting a variety of pathways in relieving the clinical symptoms of inflammation in acute EAE model. Therefore, using molecules that target different molecular pathways can be beneficial for exploring novel therapeutic approaches for MS treatment.

  12. Modulation of microglial/macrophage activation by macrophage inhibitory factor (TKP or tuftsin (TKPR attenuates the disease course of experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Tsirka Stella E

    2007-07-01

    Full Text Available Abstract Background Myelin Oligodendrocyte Glycoprotein (MOG-induced experimental autoimmune encephalomyelitis (EAE is the most commonly used mouse model for multiple sclerosis (MS. During the of progression of EAE, microglia, the immunocompetent cells of the brain, become activated and accumulate around demyelinated lesions. Microglial activation is mediated by the extracellular protease tissue Plasminogen Activator (tPA, and mice lacking tPA display altered EAE progression. In this study, we have used pharmacological inhibitors and stimulators of microglial/macrophage activation to examine the temporal requirement for microglial activation in EAE progression and to determine whether such approaches might potentially be of therapeutic value. Results Intervention using the tripeptide macrophage/microglia inhibitory factor MIF (TKP and the tetrapeptide macrophage/microglial stimulator tuftsin (TKPR attenuated EAE symptoms and revealed that the timing of macrophage/microglial activation is critical for the clinical outcome of EAE. We show that the disease progression can potentially be manipulated favorably at early stages by altering the timing of microglial activation, which in turn alters the systemic immune response to favor upregulation of T helper cell 2 genes that promote recovery from EAE. Conclusion Preventative and therapeutic modulation of macrophage/microglial activity significantly alters the outcome of EAE at symptomatic stages. Specific molecular targets have been identified that represent potential avenues of exploration for the treatment and prevention of MS.

  13. An increase in tolerogenic dendritic cell and natural regulatory T cell numbers during experimental autoimmune encephalomyelitis in Rras-/- mice results in attenuated disease.

    Science.gov (United States)

    Ray, Avijit; Basu, Sreemanti; Miller, Nichole M; Chan, Andrew M; Dittel, Bonnie N

    2014-06-01

    R-Ras is a member of the Ras superfamily of small GTPases, which are regulators of various cellular processes, including adhesion, survival, proliferation, trafficking, and cytokine production. R-Ras is expressed by immune cells and has been shown to modulate dendritic cell (DC) function in vitro and has been associated with liver autoimmunity. We used Rras-deficient mice to study the mechanism whereby R-Ras contributes to autoimmunity using experimental autoimmune encephalomyelitis (EAE), a mouse model of the CNS autoimmune disease multiple sclerosis. We found that a lack of R-Ras in peripheral immune cells resulted in attenuated EAE disease. Further investigation revealed that, during EAE, absence of R-Ras promoted the formation of MHC II(low) DC concomitant with a significant increase in proliferation of natural regulatory T cells, resulting in an increase in their cell numbers in the periphery. Our study suggests a novel role for R-Ras in promoting autoimmunity through negative regulation of natural regulatory T cell numbers by inhibiting the development of MHCII(low) DC with tolerogenic potential.

  14. D-Pinitol attenuates 7, 12 dimethylbenz [a] anthracene induced hazards through modulating protein bound carbohydrates, adenosine triphosphatases and lysosomal enzymes during experimental mammary carcinogenesis.

    Science.gov (United States)

    Rengarajan, Thamaraiselvan; Nandakumar, Natarajan; Balasubramanian, Maruthaiveeran Periyasamy

    2012-01-01

    We have reported here that the ameliorative potentials of D-Pinitol during 7, 12-Dimethylbenz [a] anthracene induced experimental breast carcinogenesis. DMBA is a potent organ specific carcinogen which is widely employed to induce mammary carcinoma in rats. D-Pinitol a natural inositol has been reported to found in soybean with many biological functions. The female sprague dawley rats were subjected to carcinogen 7, 12-DMBA and the ameliorative potentials of dietary compound D-Pinitol was investigated with reference to cell surface glycoproteins, lysosomal enzymes and adenosine triphosphatases. Interestingly, administration of D-Pinitol was found to be significantly down regulated the breast tissue glycoproteins and lysosomal enzymes and in contrast the levels of adenosine triphosphatases were remarkably up regulated. Further, the biochemical changes were well reflected and evidenced in the histology of breast and liver tissues. Thus, it can be concluded from the present study that D-Pinitol efficiently attenuates the hazardous consequences of the environmental carcinogen 7,12-DMBA through modulating cell surface glycoproteins, membrane protective role both in lysosomal and ATPase compartment via its antioxidant nature which ultimately results in the findings of future innovative remedies for genotoxin mediated hazards.

  15. 沙利度胺对溃疡性结肠炎疗效的实验研究%Experimental research of curative effect by thalidomide for ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    夏婷婷; 徐洪雨

    2016-01-01

    Objective To observe curative effect by thalidomide for 2,4,6-trinitro-benzene-sulfonic acid (TNBS)-induced ulcerative colitis (UC) by detecting serum tumor necrosis factor-α (TNF-α) concentration in rats.Methods TNBS colitis animal model was made, and 21 rats were randomly divided into model group, sulfasalazine group and thalidomide group, with 7 rats in each group. No intervention was taken in model group. Thalidomide group received thalidomide by 200 mg/(kg·d), and sulfasalazine group received sulfasalazine by 100 mg/(kg·d). Detection was made on serum TNF-α concentration to investigate curative effect by thalidomide for UC.Results Thalidomide group had reduced diarrhea times, and some rats had positive occult blood, without any visible bloody stools. TNF-α concentrations in thalidomide group, sulfasalazine group and model group were respectively (19.51±8.06), (40.88±14.24), (115.32±9.60) pg/ml. Thalidomide group had higher reducing degree of serum TNF-α concentration than sulfasalazine group, and the difference had statistical significance (P<0.01). Conclusion Thalidomide is effective in treating UC, and it can remarkably relieve colitis. It shows better effect in reducing TNF-α concentration than sulfasalazine.%目的:通过检测大鼠血清中肿瘤坏死因子-α(TNF-α)的浓度,观察沙利度胺治疗由2,4,6-三硝基苯磺酸(TNBS)诱导的溃疡性结肠炎(UC)的疗效。方法21只TNBS结肠炎动物模型,随机分为模型组、柳氮磺吡啶组及沙利度胺组,每组7只。模型组不给予干预、沙利度胺组给予沙利度胺200 mg/(kg·d)、柳氮磺吡啶组给予柳氮磺吡啶100 mg/(kg·d),测定大鼠血清中TNF-a的浓度,探讨沙利度胺对UC的疗效。结果沙利度胺组大鼠腹泻次数减少,部分有隐血阳性,一直未出现肉眼血便。沙利度胺组、柳氮磺吡啶组、模型组大鼠TNF-a的浓度分别为(19.51±8.06)、(40.88±14.24)、(115.32±9.60)pg/ml,沙利度胺组降低血清TNF-α

  16. [A case of rifampicin associated Pseudomembranous colitis].

    Science.gov (United States)

    Kim, Jae Hi; Park, Jin Hyung

    2004-06-01

    Pseudomembranous colitis is a dangerous but unusual side effect of antibiotics usage. We report a case of pseudomembranous colitis that developed in a 50-year-old female patient with diabetes mellitus during first line anti-tuberculous therapy including rifampicin. The patient was diagnosed with active pulmonary tuberculosis 70 days earlier. On admission, she suffered intermittent abdominal pain and watery diarrhea for 2 weeks. Colonoscopy revealed exudative, punctuate, raised plaques with skip areas or edematous hyperemic mucosa, and histopathologic findings were consistent with pseudomembranous colitis with typical volcano-like exudate. Symptoms improved on treatment with metronidazole. There was no recurrence after reinstitution of the anti-tuberculous agents excluding rifampicin. In patients with persistent diarrhea receiving anti-tuberculosis treatment, rifampicin associated pseudomembranous colitis should always be kept in mind.

  17. Intestinal microecology in rats with ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    韩晓霞

    2013-01-01

    Objective To study the abundance and diversity ofthe gut flora in rats with dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)to provide new knowledge about the pathogenesis of this disease.Methods Twenty-six

  18. Exploring the ameliorative potential of Punica granatum in dextran sulfate sodium induced ulcerative colitis in mice.

    Science.gov (United States)

    Singh, Kavinder; Jaggi, Amteshwar Singh; Singh, Nirmal

    2009-11-01

    The present study was designed to investigate the ameliorative potential of Punica granatum in dextran sulfate sodium (DSS) induced ulcerative colitis. DSS (2%) was administered orally in drinking water for 7 days to induce ulcerative colitis. The extent and severity of ulceration was analysed macroscopically, histopathologically and using a disease activity index. Myeloperoxidase (MPO), a specific marker of inflammation; histamine, a marker of mast cell degranulation; superoxide anion generation and, lipid peroxides were analysed. Administration of DSS resulted in a significant development of ulceration in the colon along with a rise in histamine, MPO activity and oxidative stress. Treatment with Punica granatum extract and its ellagic acid rich fraction (100 mg/kg and 200 mg/kg p.o.) significantly attenuated DSS-induced colonic inflammation along with attenuation of histamine, MPO and oxidative stress. The antiulcerative effect of Punica granatum extract and its ellagic acid rich fraction were comparable to sulphasalazine (100 mg/kg, p.o.) and sodium cromoglycate (40 mg/kg i.p). It is concluded that Punica granatum has a potential for ameliorating DSS-induced colitis and its ellagic acid rich fraction may be responsible for this effect. Further, the antiulcerative effects may be attributed to mast cell stabilizing, antiinflammatory and antioxidant actions.

  19. An orally active Cannabis extract with high content in cannabidiol attenuates chemical induced intestinal inflammation and hypermotility in the mouse

    Directory of Open Access Journals (Sweden)

    Ester Pagano

    2016-10-01

    Full Text Available Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD, here named CBD BDS for CBD botanical drug substance, on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS. Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol. The amounts of CBD in the colon, brain and liver after the oral treatments were measured by HPLC coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion or orally (only at one dose. In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

  20. The economics of adalimumab for ulcerative colitis.

    Science.gov (United States)

    Xie, Feng

    2015-06-01

    Ulcerative colitis is a chronic inflammatory disease, characterized by diffuse mucosal inflammation in the colon. Adalimumab, as a TNF-α blocker, offers a safe and efficacious treatment option for patients with moderate to severe ulcerative colitis and refractory or intolerant to conventional medications; however, its cost-effectiveness profile has not yet been well established. Future economic evaluations should choose appropriate comparators in the context of target-reimbursement decision making and focus on cost-effectiveness over a long time horizon.

  1. Acute Ischaemic Colitis- A Case Report

    Directory of Open Access Journals (Sweden)

    M Basra

    2012-03-01

    Full Text Available Acute ischaemic colitis (AIC is being increasingly recognised as an uncommon cause of abdominal pain associated with fresh bleeding per rectum. It is paramount to maintain a high index of suspicion and adopt appropriate management strategies to avoid complications and inappropriate interventions. In this paper, we describe a case of AIC and review literature pertinent to the management of this condition. Keywords: Ischaemic colitis, acute abdomen, management.

  2. Intestinal microbiota and ulcerative colitis.

    Science.gov (United States)

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota.

  3. Allergic colitis: a mimic of Hirschsprung disease

    Energy Technology Data Exchange (ETDEWEB)

    Bloom, D.A. [Department of Radiology, Children`s Radiological Institute, Columbus Children`s Hospital, OH (United States); Buonomo, C. [Department of Radiology, Children`s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Fishman, S.J. [Department of Surgery, Children`s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Furuta, G.; Nurko, S. [Department of Gastroenterology, Children`s Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    1999-01-01

    Background. Allergy to cow milk protein is a common cause of gastrointestinal symptoms in infancy. Milk allergy is usually a clinical diagnosis, and thus there have been few reports of the radiographic findings. Objective. To describe the barium enema findings of allergic colitis and differentiate them from Hirschsprung disease. Materials and methods. Four infants (age range 7 days-5 weeks) with constipation underwent barium enema to exclude Hirschsprung disease. Radiographic findings were correlated with the pathologic specimens from suction rectal biopsy. Results. All enemas revealed irregular narrowing of the rectum and a transition zone. Rectal biopsies in each case demonstrated ganglion cells and evidence of an allergic colitis, with inflammatory infiltrates in the lamina propria. A diagnosis of milk allergy colitis was made and symptoms resolved after removal of milk from the diet. Conclusions. Milk allergy is common in infancy. The rectum is a primary target organ, with allergic colitis often diagnosed on clinical grounds alone. However, a child with allergic colitis may be referred to radiology for barium enema, especially if constipation is present. The radiologist should be aware of the unique imaging findings of allergic colitis, so as to avoid confusion with Hirschsprung disease and perhaps an unnecessary rectal biopsy. (orig.) With 4 figs., 1 tab., 17 refs.

  4. Colitis associated with biological agents

    Institute of Scientific and Technical Information of China (English)

    Hugh James Freeman

    2012-01-01

    In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occasionally,fatal.Other agents include rituximab (an antiCD20 monoclonal antibody),bevacizumab (a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    with ulcerative colitis, 10 patients with collagenous colitis and 20 controls with uninflamed mucosa. METHODS: The tip of a Teflon tube was placed in the caecum during colonoscopy. Subsequently, argon was infused at a constant rate for 70-180 min. Argon and NO in gas sampled from the rectum were measured...

  6. Lansoprazole-associated collagenous colitis: Diffuse mucosal cloudiness mimicking ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Mitsuro Chiba; Takeshi Sugawara; Haruhiko Tozawa; Hidehiko Tsuda; Toru Abe; Takuo Tokairin; Iwao Ono; Eriko Ushiyama

    2009-01-01

    There have only been a few reports on lansoprazoleassociated collagenous colitis. Colonic mucosa of collagenous colitis is known to be endoscopically normal. We present a case of collagenous colitis where the mucosa showed diffuse cloudiness mimicking ulcerative colitis. A 70-year-old woman developed watery diarrhea four to nine times a day. She had interstitial pneumonia at 67 and reflux esophagitis at 70 years. Lansoprazole 30 mg/d had been prescribed for reflux esophagitis for nearly 6 mo. Lansoprazole was withdrawn due to its possible side effect of diarrhea. Colonoscopy disclosed diffuse cloudiness of the mucosa which suggested ulcerative colitis. Consequently sulfasalazine 2 g/d was started. The patient's diarrhea dramatically disappeared on the following day. However, biopsy specimens showed subepithelial collagenous thickening and infiltration of inflammatory cells in the lamina propria, confirming the diagnosis of collagenous colitis. One month after sulfasalazine therapy was initiated, colonoscopic and histological abnormalities resolved completely. Five months later the diarrhea recurred. The findings on colonoscopy and histology were the same as before, confirming a diagnosis of collagenous colitis relapse. We found that the patient had begun to take lansoprazole again 3 mo ahead of the recent diarrhea. Withdrawal of lansoprazole promptly resolved the diarrhea. Endoscopic and histological abnormalities were also completely resolved, similar to the first episode. Retrospectively, the date of commencement of sulfasalazine and discontinuation of lansoprazole in the first episode was found to be the same. We conclude that this patient had lansoprazole-associated collagenous colitis.

  7. Anti-Inflammatory Effect of Erythropoietin in the TNBS-induced Colitis.

    Science.gov (United States)

    Mateus, Vanessa; Rocha, João; Alves, Paula; Mota-Filipe, Helder; Sepodes, Bruno; Pinto, Rui Manuel Amaro

    2017-02-01

    Erythropoietin is a potent stimulator of erythroid progenitor cells, which is able to inhibit NF-kB activation, due to its pleiotropic properties, thus promoting an anti-inflammatory effect. As inflammatory bowel disease is a chronic disease with reduced quality of life, and the current pharmacotherapy only induces or maintains the patient in remission, there is a crucial need of new pharmacological approaches. The main objective of this study was to evaluate the effect of erythropoietin in the TNBS-induced colitis model in mice with a normal intestinal flora. Mice with TNBS-induced colitis were treated with a daily dose of erythropoietin at 500 IU/kg bw/day and 1000 IU/Kg bw/day IP during 4 days. As to clinical symptoms/signs, erythropoietin attenuated the decreased body-weight and reduced diarrhoea and oedema of the anus registered in the non-treated mice group in a dose-dependent manner. The anti-inflammatory properties of erythropoietin in the TNBS-induced colitis were confirmed by suppression of pro-inflammatory mediators, such as TNF-α, IL-1β and MPO, as well as a significant increase in the anti-inflammatory cytokine, IL-10, was promoted. These treated mice also presented a reduction in haemoglobin faecal and ALP, suggesting a beneficial effect of erythropoietin in the haemorrhagic focus and destruction of the enterocyte associated with the colon injury induced by TNBS, respectively. The histopathological score was reduced after treatment with erythropoietin, decreasing the severity and extension of the colitis. Furthermore, renal and hepatic biomarkers, as well as haematocrit concentration, remained stabilized after treatment. In conclusion, erythropoietin reduces the inflammatory response associated with TNBS-induced colitis in mice.

  8. Low dose dextromethorphan attenuates moderate experimental autoimmune encephalomyelitis by inhibiting NOX2 and reducing peripheral immune cells infiltration in the spinal cord

    Science.gov (United States)

    Chechneva, Olga V.; Mayrhofer, Florian; Daugherty, Daniel J.; Pleasure, David E.; Hong, Jau-Shyong; Deng, Wenbin

    2011-01-01

    Dextromethorphan (DM) is a dextrorotary morphinan and a widely used component of cough medicine. Relatively high doses of DM in combination with quinidine are used for the treatment of mood disorders for patients with multiple sclerosis (MS). However, at lower doses, morphinans exert anti-inflammatory activities through the inhibition of NOX2-dependent superoxide production in activated microglia. Here we investigated the effects of high (10 mg/kg, i.p., “DM-10”) and low (0.1 mg/kg, i.p., “DM-0.1”) doses of DM on the development and progression of mouse experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We found no protection by high dose DM treatment. Interestingly, a minor late attenuation by low dose DM treatment was seen in severe EAE that was characterized by a chronic disease course and a massive spinal cord infiltration of CD45+ cells including T-lymphocytes, macrophages and neutrophils. Furthermore, in a less severe form of EAE, where lower levels of CD4+ and CD8+ T-cells, Iba1+ microglia/macrophages and no significant infiltration of neutrophils were seen in the spinal cord, the treatment with DM-0.1 was remarkably more beneficial. The effect was the most significant at the peak of disease and was associated with an inhibition of NOX2 expression and a decrease in infiltration of monocytes and lymphocytes into the spinal cord. In addition, chronic treatment with low dose DM resulted in decreased demyelination and reduced axonal loss in the lumbar spinal cord. Our study is the first report to show that low dose DM is effective in treating EAE of moderate severity. Our findings reveal that low dose morphinan DM treatment may represent a new promising protective strategy for treating MS. PMID:21704706

  9. Experimental infection of commercial layers with wild or attenuated Salmonella Gallinarum mutant strains: anatomic pathology, total blood cell count and serum protein levels

    Directory of Open Access Journals (Sweden)

    KO Garcia

    2013-06-01

    Full Text Available The aim of the present study was to comparatively evaluate hemogram, blood serum components and anatomopathologic alterations in commercial layers experimentally challenged with an attenuated vaccine candidate strain (SG∆cobS∆cbiA and other two pathogenic strains (SGDcobS and SGNalr of Gallinarum (SG. In total, 280 commercial layers were randomly divided into 4 groups (G1, G2, G3 and G4. At five days of age, birds from groups G1 received approximately 107 colony forming units (CFU of SGDcobS; meanwhile birds from group G2 and G3 received the same dose of SGNalr and SG∆cobS∆cbiA, respectively. Birds from G4 were not infected. At 24 hours before (DBI and 24 hours after (1 DAI, and three (3 DAI, five (5 DAI, seven (7 DAI ten (10 DAI, and fifteen (15 DAI days after the infection, 10 birds of each group were humanely killed and blood samples collected to hematological and serum tests. Samples of liver, spleen, thymus, bursa of Fabricius, kidney and heart were also collected for the histological examination. Birds inoculated with SGDcobS and SGNalr showed similar alterations in hemogram, blood serum components and anatomopathologic exams. On the other hand, the exams of birds inoculated with SG∆cobS∆cbiA strain were similar to those of the uninfected birds. However, changes could be noticed in levels of uric acid and cholesterol during the course of the infection of birds from G3. Decrease in levels of light IgG 3 DAI was also observed in birds from this group. Pyknosis in kidney cells was a microscopic alteration found in birds from G3. Further studies must be done to verify if these alterations will not interfere in the performance of the vaccinate birds with SG∆cobS∆cbiA strain.

  10. Curcumin inhibits trinitrobenzene sulphonic acid-induced colitis in rats by activation of peroxisome proliferator-activated receptor gamma.

    Science.gov (United States)

    Zhang, Ming; Deng, Changsheng; Zheng, Jiaju; Xia, Jian; Sheng, Dan

    2006-08-01

    Curcumin is a widely used spice with anti-inflammatory and anti-cancer properties. It has been reported that curcumin held therapeutic effects on experimental colitis by inhibition of nuclear factor kappa B (NF-kappaB). The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor with anti-tumor and anti-inflammatory effects and its activation may inhibit the nuclear translocation of NF-kappaB. Several studies have shown that PPARgamma ligands had an important therapeutic effect in colitis. However there is no report about the alteration of PPARgamma in trinitrobenzene sulphonic acid (TNBS)-induced colitis treated with curcumin. In this study, we administered curcumin (30 mg/kg/day) by intraperitoneal injection immediately after colitis was induced and the injection lasted for two weeks. have evaluated the effects of curcumin on the colitis induced by trinitrobenzene sulphonic acid (TNBS). Curcumin (30 mg/kg d) was administered by intraperitoneal just after colitis was induced and lasted for two weeks. Therapeutic effects of dexamethasone (Dex, 2 mg/kg d) alone and the combined effects of curcumin+Dex were also examined. We found that curcumin improved long-term survival rate of disease-bearing rats, promoted rat body weight recovery, and decreased macroscopic scores of the colitis. The expression levels of PPARgamma, 15-deoxy-D12,14-prostaglandin J(2) (15d-PGJ(2)) and prostaglandin E(2) (PGE(2)) were all increased, but the expression level of cyclooxygenase-2 (COX-2) was decreased in rats after administration of curcumin. Treatment with Dex improved PPARgamma expression and inhibited the expression of COX-2, 15d-PGJ(2) and PGE(2). Combined effects of curcumin+Dex were similar to that of Dex. In summary, curcumin showed therapeutic effects on TNBS-induced colitis and the mechanisms by which curcumin exerts its effects may involve activation of PPARgamma and its ligands.

  11. Infliximab and complications after colectomy in patients with ulcerative colitis

    DEFF Research Database (Denmark)

    Bregnbak, David; Mortensen, Christian; Bendtsen, Flemming

    2012-01-01

    Infliximab treatment may increase the risk of subsequent postoperative complications in patients with ulcerative colitis. The main purpose of the present study therefore was to assess postoperative complications in patients who have undergone colectomy for ulcerative colitis with and without...

  12. Vedolizumab as induction and maintenance therapy for ulcerative colitis

    DEFF Research Database (Denmark)

    Feagan, Brian G; Rutgeerts, Paul; Sands, Bruce E

    2013-01-01

    Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.......Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis....

  13. Cytokine Expression of Microscopic Colitis Including Interleukin-17

    OpenAIRE

    Park, Eunkyoung; Park, Young Sook; Park, Dae Rim; Jung, Sung Ae; Han, Dong Soo; Jang, Byung Ik; Kim, Young Ho; Kim, Won Ho; Jo, Yun Ju; Lee, Ki Ho; Lee, Won Mi; Kim, Eun Kyung; Koo, Hae Soo

    2014-01-01

    Background/Aims Microscopic colitis is characterized by chronic watery diarrhea with specific pathological changes that can be diagnosed by microscopic examination. We performed immunohistochemical analysis of proinflammatory cytokines to investigate the pathogenic mechanism of microscopic colitis. Methods This study consisted of six patients with lymphocytic colitis, six patients with collagenous colitis, and six patients with functional diarrhea but normal pathology. We performed an immunoh...

  14. Colitis promotes adaptation of an intestinal nematode: a Heligmosomoides polygyrus mouse model system.

    Directory of Open Access Journals (Sweden)

    Katarzyna Donskow-Łysoniewska

    Full Text Available The precise mechanism of the very effective therapeutic effect of gastrointestinal nematodes on some autoimmune diseases is not clearly understood and is currently being intensively investigated. Treatment with living helminths has been initiated to reverse intestinal immune-mediated diseases in humans. However, little attention has been paid to the phenotype of nematodes in the IBD-affected gut and the consequences of nematode adaptation. In the present study, exposure of Heligmosomoides polygyrus larvae to the changed cytokine milieu of the intestine during colitis reduced inflammation in an experimental model of dextran sulphate sodium (DSS- induced colitis, but increased nematode establishment in the moderate-responder BALB/c mouse strain. We used mass spectrometry in combination with two-dimensional Western blotting to determine changes in protein expression and changes in nematode antigens recognized by IgG1 in mice with colitis. We show that nematode larvae immunogenicity is changed by colitis as soon as 6 days post-infection; IgG1 did not recognize highly conserved proteins Lev-11 (isoform 1 of tropomyosin α1 chain, actin-4 isoform or FTT-2 isoform a (14-3-3 family protein. These results indicate that changes in the small intestine provoked by colitis directly influence the nematode proteome. The unrecognized proteins seem to be key antigenic epitopes able to induce protective immune responses. The proteome changes were associated with weak immune recognition and increased larval adaptation and worm growth, altered localization in the intestine and increased survival of males but reduced worm fecundity. In this report, the mechanisms influencing nematode survival and the consequences of changed immunogenicity that reflect the immune response at the site colonized by the parasite in mice with colitis are described. The results are relevant to the use of live parasites to ameliorate IBD.

  15. Repeated Predictable Stress Causes Resilience against Colitis-Induced Behavioral Changes in Mice

    Directory of Open Access Journals (Sweden)

    Ahmed M Hassan

    2014-11-01

    Full Text Available Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2 % in drinking water decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and social interaction tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY, a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis.

  16. Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Xiao-chang LIU; Qiao MEI; Jian-ming XU; Jing HU

    2009-01-01

    Aim:To investigate the effect of balsalazine treatment on intestinal mucosal permeability in dextran sulfate sodium (DSS)-induced colitis and to determine the mechanism of the balsalazine-induced changes.Methods:Experimental colitis was induced in C57BL/6J mice by the administration of 5% DSS.Balsalazine was administered intragastrically at doses of 42,141,and 423 mg/kg.The disease activity index (DAI) score was evaluated and colon tissue was collected for the assessment of histological changes.The amount of malondialdehyde (MDA) in the colon was determined,along with the activity of myeloperoxidase (MPO),superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).Mucosa from the small intestine was collected to determine the levels of tumor necrosis factor (TNF)-α and interferon (IFN)-Y.The mucosa was ultrastructurally examined with transmission electron microscopy and intestinal permeability was assayed using Evans blue.Results:Balsalazine was found to reduce the DAI score and the histological index (HI) score,decrease the MDA content and the activity of MPO,and increase the activity of SOD and GSH-Px in colitis mice.At the same time,balsalazine ameliorated microvillus and tight junction structure,resulting in a decrease in the amount of Evans blue permeating into the intestinal wall and the levels of TNF-α and IFN-Y in colitis mice.Conclusion:In colitis mice,the anti-colitis effect of balsalazine results in a decrease in intestinal mucosal permeability.The mechanism of this effect is partly associated with balsalazine's antioxidative and anti-inflammatory effects.

  17. Collagenous colitis as a possible cause of toxic megacolon.

    LENUS (Irish Health Repository)

    Fitzgerald, S C

    2009-03-01

    Collagenous colitis is a microscopic colitis characterized by normal appearing colonic mucosa on endoscopy. It is regarded as a clinically benign disease which rarely results in serious complications. We report a case of toxic megacolon occurring in a patient with collagenous colitis. This is the first reported case of toxic megacolon occurring in this subset of patients.

  18. Paradoxical regulation of ChAT and nNOS expression in animal models of Crohn's colitis and ulcerative colitis

    OpenAIRE

    Winston, John H.; Li, Qingjie; Sarna, Sushil K.

    2013-01-01

    Morphological and functional changes in the enteric nervous system (ENS) have been reported in inflammatory bowel disease. We examined the effects of inflammation on the expression of choline acetyltransferase (ChAT) and nNOS in the muscularis externae of two models of colonic inflammation, trinitrobenzene sulfonic acid (TNBS)-induced colitis, which models Crohn's disease-like inflammation, and DSS-induced colitis, which models ulcerative Colitis-like inflammation. In TNBS colitis, we observe...

  19. 粪菌移植在小鼠实验性结肠炎中的疗效研究%Effect of Fecal Bacteria Transplantation on Experimental Colitis in Mice

    Institute of Scientific and Technical Information of China (English)

    姬盼盼; 周中银; 李櫆; 操寄望; 罗和生

    2016-01-01

    目的 观察粪菌移植(fecal microbiota transplantation,FMT)对葡聚糖硫酸钠(dextran sulfate sodium,DSS)诱导的小鼠结肠炎的影响,探讨FMT对结肠炎的治疗作用和可能机制.方法 将小鼠分为4组:正常对照组、DSS组、美沙拉嗪(又叫5-氨基水杨酸,5-aminosalicylic acid,5-ASA)组、FMT组.除正常对照组外,其余3组小鼠连续饮用3%DSS水7天,建立急性溃疡性结肠炎(ulcerative colitis,UC)模型,同时DSS组、5-ASA组及FMT组于实验第1、3、5、7天分别给予0.5%羧甲基纤维素钠(Carboxymethylcellulose sodium,CMC-Na)、5-ASA及粪菌液灌肠.每天观察各组疾病活动指数(disease activity index,DAI),于实验第8天处死小鼠,测量结肠长度,检测结肠组织中中性细胞髓过氧化物酶(myeloperoxidase,MPO)活力,肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)、白介素1β(interleukin-1 beta,IL-1β)、白介素10(interleukin-10,IL-10)的含量.结果 与模型组相比,FMT可改善小鼠结肠组织炎症程度,降低MPO活力(P<0.05),减少组织TNF-α、IL-1β的含量(P<0.05),升高IL-10的含量(P<0.05).结论 FMT对小鼠实验性结肠炎有治疗效果,可能通过重建肠道菌群,调节肠道T细胞免疫稳态来发挥治疗作用.

  20. Golimumab in unresponsive ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Lippert E

    2014-05-01

    Full Text Available Elisabeth Lippert, Martina Müller, Claudia Ott University Hospital Regensburg, Department of Internal Medicine I, Regensburg, Germany Abstract: Ulcerative colitis (UC is a chronic inflammation mainly affecting the colon mucosa. It predominantly occurs in younger patients. Until recently, the main goals in the treatment of UC were to temper the symptoms, such as diarrhea, pain, and weight loss, by using mesalazine and steroids. With newer medications, such as immunomodulators (thiopurines and the biologics providing blockade of tumor necrosis factor (TNF, the goals of the therapy in UC have changed to long-term remission and mucosal healing. The first available anti-TNF therapy in UC included infusion therapy with infliximab every few weeks. In 2012, subcutaneously administered adalimumab gained approval for the treatment of UC in Germany. In patients with a mild disease, therapy with mesalazine, orally or topically, can be sufficient. In patients with moderate to severe disease, therapy with azathioprine or anti-TNF is often required to reach disease control; however, this is only efficient in about two-thirds of patients. Some patients either show no response or a lost response while on treatment. So, further medical options are warranted in the treatment of UC. With golimumab, a new approach in the treatment of mild to moderate UC recently became available in Germany and is a promising new option in the therapy regimen for patients with UC. Keywords: anti-TNF, biological therapy, inflammatory bowel disease

  1. Effects of triptolide on the expression of intestinal mucosa IL-4 and IL-13 in experi-mental colitis rats%雷公藤甲素对大鼠实验性结肠炎组织中IL-4、IL-13表达的影响

    Institute of Scientific and Technical Information of China (English)

    杨立; 肖明明; 桑力轩; 李岩; 邢煜; 王岩; 姚远

    2015-01-01

    目的 探讨雷公藤甲素对三硝基苯磺酸钠( TNBS)诱导的大鼠结肠炎的疗效,以及对炎性细胞因子IL-4、IL-13表达的影响. 方法 成年SD大鼠18只,随机分为正常对照组( C组)、TNBS模型组( D1组)、雷公藤甲素组( TP组). 观察大鼠的一般情况,比较结肠组织炎症程度. HE染色观察大鼠结肠组织形态学变化.用反转录聚合酶链反应( RT-PCR)和Western blot( WB)法检测大鼠结肠组织IL-4和IL-13的表达水平. 结果PCR和WB法检测结果表明,C组结肠组织 IL-4、IL-13 的表达水平最高,D1 组表达最低,TP组介于两者之间.结论 雷公藤甲素能有效治疗TNBS诱导的大鼠结肠炎,其作用机制可能与雷公藤甲素上调大鼠结肠黏膜抑炎因子IL-4、IL-13的表达,抑制炎症的发生发展有关.%Objective To evaluate the curative effect of triptolide on TNBS induced colitis and the expression of intestinal mucosa IL-4 and IL-13 in experimental colitis rats and to investigate the underlying mechanisms. Methods 18 adult Sprague-Dawley rats were randomized into three groups:normal control group ( group C ) , model group (group D1),tripotlide treatment group (group TP). The general status of the rats was observed,and the histopathologic changes in the colon were examined. Reverse transcription-polymerase chain reaction ( PCR) and Western blot ( WB) techniques were used to detect the expression of IL-4 and IL-13. Results PCR and WB methods showed that the ex-pression levels of IL-4 and IL-13 in group C were higher than those of group D1 and group TP(P<0. 05),and the ex-pression levels in group D1 were lover than those of group TP ( P<0. 05). Conclusion Triptolide could effectively improve the TNBS-induced colitis in rats by promoting the expression of IL-4 and IL-13 and inhibiting the development of inflammation.

  2. Therapeutic and prophylactic thalidomide in TNBS-induced colitis: Synergistic effects on TNF-α, IL-12 and VEGF production

    Institute of Scientific and Technical Information of China (English)

    Ana Teresa Carvalho; Cláudio Tortori; Ilana Dines; Jane Carvalho; Eduardo Rocha; Celeste Elia; Heitor Souza; Antonio Jose Carneiro; Morgana Castelo-Branco; Kalil Madi; Alberto Schanaider; Flavia Silva; Fernando Antonio Pereira Jú'nior; Márcia G Pereira

    2007-01-01

    AIM: To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor α (TNF-α), IL-12, and vascular endothelial growth factor (VEGF), hallmarks of intestinal inflammation in Crohn's disease (CD).METHODS: Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4+ T cells, macrophages, and VEGF+ cells were detected by immunohistochemistry. TNF-α and IL-12 were quantified in the supernatant of organ cultures by ELISA.RESULTS: Significant reduction in the inflammatory score and in the percentage of VEGF+ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-α and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide.TNF-α levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-α and IL-12 were significantly correlated with the inflammatory score and the number of VEGF+ cells.CONCLUSION: Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-α, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.

  3. Amyloid Goiter Secondary to Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Bunyamin Aydin

    2016-01-01

    Full Text Available Diffuse amyloid goiter (AG is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn’s disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis.

  4. Diagnosis and management of microscopic colitis

    Institute of Scientific and Technical Information of China (English)

    Curt Tysk; Johan Bohr; Nils Nyhlin; Anna Wickbom; Sune Eriksson

    2008-01-01

    Microscopic colitis,comprising collagenous and lymphocytic colitis,is characterized clinically by chronic watery diarrhea,and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination.The annual incidence of each disorder is 4-6/100000 inhabitants,with a peak incidence in 60-70-year-old individuals and a noticeable female predominance for collagenous colitis.The etiology is unknown.Chronic diarrhea,abdominal pain,weight loss,fatigue and fecal incontinence are common symptoms,which impair the health-related quality of life of the patient.There is an association with other autoimmune disorders such as celiac disease,diabetes mellitus,thyroid disorders and arthritis.Budesonide is the best-documented shortterm treatment,but the optimal long-term strategy needs further study.The long-term prognosis is good and the risk of complications including colonic cancer is low.

  5. Infliximab to treat severe ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Dídia Bisamra Cury; Marcelo de Souza Cury; Geraldo Vinicius Hemerly Elias; Sender Jankiel Mizsputen

    2009-01-01

    A 48-year-old female with severe ulcerative colitis refractory to conventional therapy was referred to our facility for management. The patient showed extensive ulcerative colitis since the age of 20 years and had failed therapy with 5-aminosalicylic acid agents and azathioprine. The disease remained active despite treatment with steroids and cyclosporine. The clinical and endoscopic parameters were consistent with severe disease. Infectious precipitants were ruled out. Given the severity of the disease and in order to avoid a colectomy, we started the patient on infliximab therapy. A dramatic clinical and endoscopic response was observed and she remained in remission at the end of a 1-year follow-up period. We discuss findings in the literature regarding the use of infliximab therapy in patients with ulcerative colitis who have failed steroids and cyclosporine.

  6. 1,4-Dihydroxy-2-naphthoic acid from Propionibacterium freudenreichii reduces inflammation in interleukin-10-deficient mice with colitis by suppressing macrophage-derived proinflammatory cytokines.

    Science.gov (United States)

    Okada, Yoshikiyo; Tsuzuki, Yoshikazu; Narimatsu, Kazuyuki; Sato, Hirokazu; Ueda, Toshihide; Hozumi, Hideaki; Sato, Shingo; Hokari, Ryota; Kurihara, Chie; Komoto, Shunsuke; Watanabe, Chikako; Tomita, Kengo; Kawaguchi, Atsushi; Nagao, Shigeaki; Miura, Soichiro

    2013-09-01

    The anti-inflammatory mechanism of prebiotics has recently been shown to have an impact on the host immune system. DHNA from Propionibacterium freudenreichii is known to promote the proliferation of Bifidobacterium and can ameliorate colitis, although its mode of action remains unknown. In this study, we investigated whether DHNA attenuates inflammation in piroxicam-treated IL-10(-/-) mice, particularly focusing on the changes of the host immune mechanism. DHNA was administered to IL-10(-/-) mice with colitis, and the expression of adhesion molecules and mRNA levels of proinflammatory cytokines were determined. DHNA pretreatment attenuated the piroxicam-induced histological changes. The increased F4/80-positive cell infiltration and VCAM-1 expression were decreased by DHNA administration. The increased mRNA levels of proinflammatory cytokines were also suppressed by DHNA. In in vitro experiments, increased mRNA levels of proinflammatory cytokines after endotoxin exposure were decreased significantly by DHNA pretreatment in RAW264.7, a macrophage cell line, and IL-10(-/-) mice BMMs, whereas the expression of VCAM-1 in bEnd.3 cells, a endothelial cell line, was not affected. Taken together, these findings suggest that administration of DHNA is useful for the treatment of colitis in piroxicam-treated IL-10(-/-) mice and that attenuation of colitis by DHNA may partly be a result of its direct action on intestinal macrophages to inhibit proinflammatory cytokine production.

  7. Small-bowel permeability in collagenous colitis

    DEFF Research Database (Denmark)

    Wildt, Signe; Madsen, Jan L; Rumessen, Jüri J

    2006-01-01

    OBJECTIVE: Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestin......OBJECTIVE: Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small...

  8. In-vivo monitoring of acute DSS-Colitis using Colonoscopy, high resolution Ultrasound and bench-top Magnetic Resonance Imaging in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Walldorf, J.; Hermann, M.; Pohl, S.; Zipprich, A. [Martin Luther University Halle-Wittenberg, Department of Internal Medicine I, Halle (Germany); Porzner, M.; Seufferlein, T. [University of Ulm, Department of Internal Medicine I, Ulm (Germany); Metz, H.; Maeder, K. [Martin Luther University, Institut of Pharmacy, Halle-Wittenberg (Germany); Christ, B. [University of Leipzig, Department of Surgery II, Leipzig (Germany)

    2015-10-15

    The aim of this study was to establish and evaluate (colour Doppler-) high-resolution-ultrasound (hrUS) and bench-top magnetic resonance imaging (btMRI) as new methods to monitor experimental colitis. hrUS, btMRI and endoscopy were performed in mice without colitis (n = 15), in mice with acute colitis (n = 14) and in mice with acute colitis and simultaneous treatment with infliximab (n = 19). Determination of colon wall thickness using hrUS (32 MHz) and measurement of the cross-sectional colonic areas by btMRI allowed discrimination between the treatment groups (mean a vs. b vs. c - btMRI: 922 vs. 2051 vs. 1472 pixel, hrUS: 0.26 vs. 0.45 vs. 0.31 mm). btMRI, endoscopy, hrUS and colour Doppler-hrUS correlated to histological scoring (p < 0.05), while endoscopy and btMRI correlated to post-mortem colon length (p < 0.05). The innovative in vivo techniques btMRI and hrUS are safe and technically feasible. They differentiate between distinct grades of colitis in an experimental setting, and correlate with established post-mortem parameters. In addition to endoscopic procedures, these techniques provide information regarding colon wall thickness and perfusion. Depending on the availability of these techniques, their application increases the value of in vivo monitoring in experimental acute colitis in small rodents. (orig.)

  9. Optimal management of steroid-dependent ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Khan HMW

    2015-11-01

    Full Text Available Hafiz M Waqas Khan,1 Faisal Mehmood,1 Nabeel Khan2 1Department of Medicine, King Edward Medical University, Lahore, Pakistan; 2Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia VA Medical Center, Philadelphia, PA, USA Abstract: Ulcerative colitis (UC is a chronic inflammatory condition that is variable in both extent and severity of disease as well as response to therapy. Corticosteroids (CSs were the first drugs used in the management of UC and are still used for induction of remission. However, because of their extensive side-effect profile, they are not utilized for maintenance of remission. In view of this, CS-free remission has become an important end point while evaluating therapeutic agents used in the management of UC. This review highlights the results of various studies conducted to evaluate the efficacy of different medications to attain CS-free remission in the setting of active UC. The drugs reviewed include established agents such as thiopurines, methotrexate, infliximab, adalimumab, vedolizumab, golimumab, and newer experimental agents, and if all else fails, colectomy will be performed. The efficacy of these drugs is evaluated individually. Our aim is to provide a synopsis of the work done in this field to date. Keywords: ulcerative colitis, steroid dependent, thiopurines, MTX, adalimumab, infliximab

  10. BTZO-15, an ARE-activator, ameliorates DSS- and TNBS-induced colitis in rats.

    Science.gov (United States)

    Yukitake, Hiroshi; Kimura, Haruhide; Suzuki, Hirobumi; Tajima, Yasukazu; Sato, Yoshimi; Imaeda, Toshihiro; Kajino, Masahiro; Takizawa, Masayuki

    2011-01-01

    Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that are primarily represented by ulcerative colitis and Crohn's disease. The etiology of IBD is not well understood; however, oxidative stress is considered a potential etiological and/or triggering factor for IBD. We have recently reported the identification of BTZO-1, an activator of antioxidant response element (ARE)-mediated gene expression, which protects cardiomyocytes from oxidative stress-induced insults. Here we describe the potential of BTZO-15, an active BTZO-1 derivative for ARE-activation with a favorable ADME-Tox profile, for the treatment of IBD. BTZO-15 induced expression of heme oxygenase-1 (HO-1), an ARE-regulated cytoprotective protein, and inhibited NO-induced cell death in IEC-18 cells. Large intestine shortening, rectum weight gain, diarrhea, intestinal bleeding, and an increase in rectal myeloperoxidase (MPO) activity were observed in a dextran sulfate sodium (DSS)-induced colitis rat model. Oral administration of BTZO-15 induced HO-1 expression in the rectum and attenuated DSS-induced changes. Furthermore BTZO-15 reduced the ulcerated area and rectal MPO activity in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats without affecting rectal TNF-α levels. These results suggest that BTZO-15 is a promising compound for a novel IBD therapeutic drug with ARE activation properties.

  11. BTZO-15, an ARE-activator, ameliorates DSS- and TNBS-induced colitis in rats.

    Directory of Open Access Journals (Sweden)

    Hiroshi Yukitake

    Full Text Available Inflammatory bowel disease (IBD is a group of chronic inflammatory disorders that are primarily represented by ulcerative colitis and Crohn's disease. The etiology of IBD is not well understood; however, oxidative stress is considered a potential etiological and/or triggering factor for IBD. We have recently reported the identification of BTZO-1, an activator of antioxidant response element (ARE-mediated gene expression, which protects cardiomyocytes from oxidative stress-induced insults. Here we describe the potential of BTZO-15, an active BTZO-1 derivative for ARE-activation with a favorable ADME-Tox profile, for the treatment of IBD. BTZO-15 induced expression of heme oxygenase-1 (HO-1, an ARE-regulated cytoprotective protein, and inhibited NO-induced cell death in IEC-18 cells. Large intestine shortening, rectum weight gain, diarrhea, intestinal bleeding, and an increase in rectal myeloperoxidase (MPO activity were observed in a dextran sulfate sodium (DSS-induced colitis rat model. Oral administration of BTZO-15 induced HO-1 expression in the rectum and attenuated DSS-induced changes. Furthermore BTZO-15 reduced the ulcerated area and rectal MPO activity in 2,4,6-trinitrobenzene sulfonic acid (TNBS-induced colitis rats without affecting rectal TNF-α levels. These results suggest that BTZO-15 is a promising compound for a novel IBD therapeutic drug with ARE activation properties.

  12. Drug therapy for ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Chang-Tai Xu; Shu-Yong Meng; Bo-Rong Pan

    2004-01-01

    Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. Drug therapy is not the only choice for UC treatment and medical management should be as a comprehensive whole.Azulfidine, Asacol, Pentasa, Dipentum, and Rowasa all contain 5-aminosalicylic acid (5-ASA), which is the topical anti-inflammatory ingredient. Pentasa is more commonly used in treating Crohn's ileitis because Pentasa capsules release more 5-ASA into the small intestine than Asacol tablets. Pentasa can also be used for treating mild to moderate UC. Rowasa enemas are safe and effective in treating ulcerative proctitis and proctosigmoiditis. The sulfafree 5-ASA agents (Asacol, Pentasa, Dipentum and Rowasa) have fewer side effects than sulfa-containing Azulfidine. In UC patients with moderate to severe disease and in patients who failed to respond to 5-ASA compounds,systemic (oral) corticosteroids should be used. Systemic corticosteroids (prednisone, prednisolone, cortisone, etc.)are potent and fast-acting drugs for treating UC, Crohn's ileitis and ileocolitis. Systemic corticosteroids are not effective in maintaining remission in patients with UC.Serious side effects can result from prolonged corticosteroid treatment. To minimize side effects, corticosteroids should be gradually reduced as soon as the disease remission is achieved. In patients with corticosteroid-dependent or unresponsive to corticosteroid treatment, surgery or immunomodulator is considered. Immunomodulators used for treating severe UC include azathioprine/6-MP,methotrexate, and cyclosporine. Integrated traditional Chinese and Western medicine is safe and effective in maintaining remission in patients with UC.

  13. BMP signaling in rats with TNBS-induced colitis following BMP7 therapy.

    Science.gov (United States)

    Maric, Ivana; Kucic, Natalia; Turk Wensveen, Tamara; Smoljan, Ivana; Grahovac, Blazenka; Zoricic Cvek, Sanja; Celic, Tanja; Bobinac, Dragica; Vukicevic, Slobodan

    2012-05-15

    Beyond stimulating bone formation, bone morphogenetic proteins (BMPs) are important in development, inflammation, and malignancy of the gut. We have previously shown that BMP7 has a regenerative, anti-inflammatory, and antiproliferative effect on experimental inflammatory bowel disease (IBD) in rats. To further investigate the BMP signaling pathway we monitored the effect of BMP7 therapy on the BMP signaling components in the rat colon during different stages of experimentally induced colitis by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The results showed a significantly decreased BMP7 expression in the acute phase, followed by a significantly increased BMP2 and decreased BMP6 expression during the chronic phase of colitis. BMP7 therapy influenced the expression of several BMPs with the most prominent effect on downregulation of BMP2 and upregulation of BMP4 in the chronic phase of colitis. Importantly, connective tissue growth factor and noggin expression were elevated in the acute stage and significantly decreased upon BMP7 therapy. BMP receptor I expression was unchanged, whereas BMP receptor II was decreased at day 2 and increased at days 14 and 30 of TNBS inflammation. However, an opposite pattern of expression following BMP7 therapy has been observed. BMP7 increased the expression of BR-Smad including Smad3 and Smad4. Inhibitory Smads were increased in colitis and significantly decreased following BMP7 therapy at later stages of the disease. We suggest that BMP signaling was altered during TNBS-induced colitis and was recovered with BMP7 administration, suggesting that IBD is a reversible process.

  14. An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse

    Science.gov (United States)

    Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A.; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A.; Borrelli, Francesca

    2016-01-01

    Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for “CBD botanical drug substance,” on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage – after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment. PMID:27757083

  15. An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse.

    Science.gov (United States)

    Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A; Borrelli, Francesca

    2016-01-01

    Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for "CBD botanical drug substance," on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

  16. Melatonin reduces bacterial translocation and apoptosis in trinitrobenzene sulphonic acid-induced colitis of rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM:To investigate the effects of exogenous melatonin on bacterial translocation and apoptosis in a rat ulcerative colitis model.METHODS:Rats were randomly assigned to three groups:group Ⅰ:control,group Ⅱ: experimental colitis,group Ⅲ:colitis plus melatonin treatment.On d 11 after colitis,plasma tumor necrosis factor-α,portal blood endotoxin levels,colon tissue myeloperoxidase and caspase-3 activity were measured.Bacterial translocation was quantified by blood,lymph node,liver and spleen culture.RESULTS:We observed a significantly reduced incidence of bacterial translocation to the liver,spleen,mesenteric lymph nodes,portal and systemic blood in animals treated with melatonin.Treatment with melatonin significantly decreased the caspase-3 activity in colonic tissues compared to that in trinitrobenzene sulphonic acid-treated rats (16.11 ± 2.46 vs 32.97 ± 3.91,P < 0.01).CONCLUSION:Melatonin has a protective effect on bacterial translocation and apoptosis.

  17. Resveratrol abrogates adhesion molecules and protects against TNBS-induced ulcerative colitis in rats.

    Science.gov (United States)

    Abdallah, Dalaal M; Ismael, Naglaa R

    2011-11-01

    Resveratrol, a polyphenol compound with anti-inflammatory properties, has been previously evaluated for its beneficial effects in several ulcerative colitis models. However, the current study elucidates the effect of resveratrol on adhesion molecules, as well as its antioxidant efficacy in a trinitrobenzene sulfonic acid (TNBS)-induced ulcerative-colitis model. Colitis was induced by rectal instillation of TNBS, followed by daily per os administration of either sulphasalazine (300 mg/kg) or resveratrol (2 and 10 mg/kg) for 7 days. Administration of resveratrol decreased the ulcerative area and colon mass index; these effects were further supported by the reduction in colon inflammation grades, as well as histolopathological changes, and reflected by the stalling of body mass loss. The anti-inflammatory effects of resveratrol were indicated by lowered myeloperoxidase activity, and by suppressing ICAM-1 and VCAM-1 levels in the colon and serum. In addition, it restored a reduced colonic nitric oxide level and reinstated its redox balance, as evidenced by the suppression of lipid peroxides and prevention of glutathione depletion. The anti-ulcerative effect of the higher dose of resveratrol was comparable with those of sulphasalazine. The study confirms the anti-ulcerative effect of resveratrol in TNBS-induced experimental colitis via reduction of neutrophil infiltration, inhibition of adhesive molecules, and restoration of the nitric oxide level, as well as the redox status.

  18. Inhibition of Aloperine on Dextran Sulphate Sodium-induced Chronic Colitis in C57BL/6 Mice

    Institute of Scientific and Technical Information of China (English)

    SONG Li-jun; ZHAO Wen-chang; DENG Hong-zhu

    2012-01-01

    Objective To investigate the effects of aloperine (ALO) on a model of dextran sulphate sodium (DSS)-induced chronic colitis in C57BL/6 mice.Methods Repeated colitis was induced by administration of four cycles of 4% DSS.The severity of colitis was assessed on the basis of clinical signs,ratio of colon weight and colon length,and histological grading scores.Moreover,secretory immunoglobulin A (S-IgA) and plasma haptoglobin (HP) were analyzed by enzyme-linked immunosorbent assay,and the changes of mRNA expression of ICAM-1and MIF gene in colorectal tissue were detected by quantitative reverse transcriptase real-time polymerase chain reaction using SYBR Green Ⅰ.Results ALO administration significantly attenuated the colon damage,caused substantial reductions of the rise in HP,and maintained the level of cecum S-IgA.ALO inhibited the ICAM-1mRNA expression and had no effect on MIF mRNA expression.Conclusion The effect of ALO on DSS-induced chronic colitis in mice is investigated for the first time,which suggests that ALO could be an attractive therapeutic candidate in the treatment of inflammatory bowel disease.

  19. Cerebral Arterial Thrombosis in Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Giovanni Casella

    2013-01-01

    Full Text Available Thrombosis, mainly venous, is a rare and well-recognized extraintestinal manifestation of inflammatory bowel disease (IBD. We describe a 25-year-old Caucasian man affected by ulcerative colitis and sclerosing cholangitis with an episode of right middle cerebral arterial thrombosis resolved by intraarterial thrombolysis. We perform a brief review of the International Literature.

  20. Pseudomembranous collagenous colitis with superimposed drug damage.

    Science.gov (United States)

    Villanacci, Vincenzo; Cristina, Silvia; Muscarà, Maurizio; Saettone, Silvia; Broglia, Laura; Antonelli, Elisabetta; Salemme, Marianna; Occhipinti, Pietro; Bassotti, Gabrio

    2013-11-01

    Pseudomembranous collagenous colitis is a rare pathological condition, not related to infectious agents, and characterized by thickening of the subepithelial collagen and formation of pseudomembranes. We report one such case, which responded to budesonide treatment after failures of previous approaches given, being unaware of the correct diagnosis.

  1. Pseudomembranous colitis: Not always Clostridium difficile.

    Science.gov (United States)

    Tang, Derek M; Urrunaga, Nathalie H; von Rosenvinge, Erik C

    2016-05-01

    Although Clostridium difficile infection is the cause of most cases of pseudomembranous colitis, clinicians should consider less common causes, especially if pseudomembranes are seen on endoscopy but testing remains negative for C difficile or if presumed C difficile infection does not respond to treatment. Histologic review of colonic mucosal biopsy specimens can provide clues to the underlying cause.

  2. Manipulation of enteric flora in ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Mario Guslandi

    2005-01-01

    @@ TO THE EDITOR Reviewing the available therapeutic options in the medical treatment of ulcerative colitis, Xu et al.[1], have omitted to mention an important aspect in the pharmacological management of the disease, namely the possibility to promote clinical and endoscopic improvement by manipulating the enteric flora.

  3. Colitis following fecal diversion: still a challenge

    Directory of Open Access Journals (Sweden)

    Castro Leonaldson dos Santos

    2000-01-01

    Full Text Available After fecal diversion, nonspecific colitis may be seen in the defunctionalized colon. The purpose of this prospective study is to identify specific findings that could help in the differential diagnosis between diversion colitis and other inflammatory bowel diseases in order to avoid inappropriate diagnosis and therapy. It was studied, prospectively, thirteen consecutive patients from two public hospitals of Rio de Janeiro who had undergone temporary colostomy for indications other than inflammatory bowel disease. They were submitted to endoscopy with biopsy of both proximal and distal colorectal segments, and prospectively evaluated before and after restoration of intestinal continuity. Endoscopy with biopsy of both proximal and distal excluded colorectal segments showed a nonspecific mucosal and submucosal inflammation, resembling ulcerative colitis ( p < 0.01. There was endoscopic resolution in all patients once restoration of intestinal continuity was established (p < 0.01 and also histologic improvement after the stoma closure. In conclusion there are no specific findings that make possible an unequivocal distinction between diversion colitis and other nonspecific inflammatory diseases. Diagnosis should be achieved if after stoma closure occur remission of endoscopic large bowel inflammatory signs with improvement in mucosal histologic appearance and prompt relief of clinical complaints.

  4. Vaccin-therapie bij colitis ulcerosa

    NARCIS (Netherlands)

    Lups, Sibrand

    1934-01-01

    In de Mayo Clinic te Rochester werden in de jaren 1925 tot 1931 een groot aantal patienten, lijdende aan colitis ulcerosa chronica, door Bargen met veel succes behandeld. Hij isoleerde n.l. uit de darmulcera dezer patienten een diplo-coccus, welken hij, op grond van dierexperimenten, als den verwekk

  5. Golimumab for the treatment of ulcerative colitis

    NARCIS (Netherlands)

    Lowenberg, M.; Boer, N. de; Hoentjen, F.

    2014-01-01

    The introduction of therapeutic antibodies against tumor necrosis factor (TNF) had a major impact on the treatment of ulcerative colitis (UC). Infliximab and adalimumab are powerful agents that are used for remission induction and maintenance therapy in UC and have an acceptable safety profile. Howe

  6. Future targets for immune therapy in colitis?

    DEFF Research Database (Denmark)

    Kristensen, Nanna Ny; Claesson, M H

    2008-01-01

    Crohn's disease and Ulcerative Colitis, collectively termed inflammatory bowel disease (IBD), are chronic inflammatory disorders of the bowel. It is generally accepted that the pathology associated with IBD is characterized by a hyper-reactive immune response in the gut wall directed against...

  7. Ulcerative colitis flare with splenic ven thrombosis.

    Science.gov (United States)

    Bozkurt, Huseyin Sancar; Kara, Banu; Citil, Serdal

    2015-01-01

    Patients with ulcerative colitis (UC) have an increased risk of thromboembolic events. Here, we present a 28-year-old man with active ulcerative pancolitis presenting via splenic vein thrombosis and left renal superior infarct that was not associated with a surgical procedure.

  8. Microarray Assisted Gene Discovery in Ulcerative Colitis

    DEFF Research Database (Denmark)

    Brusgaard, Klaus

    Inflammatory Bowel disease (IBD) is a condition characterised by chronic recidivous inflammation of the bowel and intestine. IBD includes chron´s disease (CD) and ulcerative colitis (UC). The combined prevalence of CD and UC are app. 1 in 500 in the general Caucasian population. In 25% of the cases...

  9. Neutrophil Extracellular Traps in Ulcerative Colitis

    DEFF Research Database (Denmark)

    Bennike, Tue Bjerg; Carlsen, Thomas Gelsing; Ellingsen, Torkell

    2015-01-01

    BACKGROUND: The etiology of the inflammatory bowel diseases, including ulcerative colitis (UC), remains incompletely explained. We hypothesized that an analysis of the UC colon proteome could reveal novel insights into the disease etiology. METHODS: Mucosal colon biopsies were taken by endoscopy...

  10. Small-bowel permeability in collagenous colitis

    DEFF Research Database (Denmark)

    Wildt, Signe; Madsen, Jan L; Rumessen, Jüri J

    2006-01-01

    Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestinal biopsies...

  11. Lymphocytic colitis: A clue to bacterial etiology

    Institute of Scientific and Technical Information of China (English)

    Thanaa EA Helal; Naglaa S Ahmed; Osama Abo El Fotoh

    2005-01-01

    AIM: To find out the role of bacteria as a possible etiological factor in lymphocytic colitis.METHODS: Twenty patients with histopathological diagnosis of lymphocytic colitis and 10 normal controls were included in this study. Colonoscopic biopsies were obtained from three sites (hepatic and splenic flexures and rectosigmoid region). Each biopsy was divided into two parts. A fresh part was incubated on special cultures for bacterial growth. The other part was used for the preparation of histologic tissue sections that were examined for the presence of bacteria with the help of Giemsa stain.RESULTS: Culture of tissue biopsies revealed bacterial growth in 18 out of 20 patients with lymphocytic colitis mostly Escherichia coli(14/18), which was found in all rectosigmoid specimens (14/14), but only in 8/14 and 6/14 of splenic and hepatic flexure specimens respectively. In two of these cases, E coliwas associated with proteus. Proteus was found only in one case, Klebsiella in two cases, and Staphylococcus aureus in one case. In the control group, only 2 out of 10 controls showed the growth of E coliin their biopsy cultures.Histopathology showed rod-shaped bacilli in the tissue sections of 12 out of 14 cases with positive E coliin their specimen's culture. None of the controls showed these bacteria in histopathological sections.CONCLUSION: This preliminary study reports an association between E coliand lymphocytic colitis, based on histological and culture observations. Serotyping and molecular studies are in process to assess the role of E coliin the pathogenesis of lymphocytic colitis.

  12. Statistical analysis of accurate prediction of local atmospheric optical attenuation with a new model according to weather together with beam wandering compensation system: a season-wise experimental investigation

    Science.gov (United States)

    Arockia Bazil Raj, A.; Padmavathi, S.

    2016-07-01

    Atmospheric parameters strongly affect the performance of Free Space Optical Communication (FSOC) system when the optical wave is propagating through the inhomogeneous turbulent medium. Developing a model to get an accurate prediction of optical attenuation according to meteorological parameters becomes significant to understand the behaviour of FSOC channel during different seasons. A dedicated free space optical link experimental set-up is developed for the range of 0.5 km at an altitude of 15.25 m. The diurnal profile of received power and corresponding meteorological parameters are continuously measured using the developed optoelectronic assembly and weather station, respectively, and stored in a data logging computer. Measured meteorological parameters (as input factors) and optical attenuation (as response factor) of size [177147 × 4] are used for linear regression analysis and to design the mathematical model that is more suitable to predict the atmospheric optical attenuation at our test field. A model that exhibits the R2 value of 98.76% and average percentage deviation of 1.59% is considered for practical implementation. The prediction accuracy of the proposed model is investigated along with the comparative results obtained from some of the existing models in terms of Root Mean Square Error (RMSE) during different local seasons in one-year period. The average RMSE value of 0.043-dB/km is obtained in the longer range dynamic of meteorological parameters variations.

  13. Tanshinone IIA Protects against Dextran Sulfate Sodium- (DSS-) Induced Colitis in Mice by Modulation of Neutrophil Infiltration and Activation.

    Science.gov (United States)

    Liu, Xiaowei; He, Haiyue; Huang, Tingting; Lei, Zhen; Liu, Fuquan; An, Guangyu; Wen, Tao

    2016-01-01

    Neutrophils play a critical role in the initiation and maintenance of intestinal inflammation. However, conventional neutrophil-targeted therapies can impair normal host defense. Tanshinone IIA has been recently revealed to act directly on neutrophils. Hence, we aimed at investigating whether Tanshinone IIA can protect against experimental colitis through modulation of neutrophils. We induced colitis in C57BL/6 mice by giving 3% dextran sulfate sodium (DSS) orally, and meanwhile, we treated mice daily with Tanshinone IIA intraperitoneally. The severity of colitis was evaluated by calculating disease activity index (DAI) and histological parameters. Neutrophil infiltration and activation in the colons of mice were measured. Moreover, whether Tanshinone IIA has direct effects on neutrophil migration and activation was determined in vitro. Our data showed that Tanshinone IIA significantly ameliorated the severity of DSS-induced colitis in mice, evidenced by the reduced DAI and improved colonic inflammation. In addition, Tanshinone IIA decreased neutrophil infiltration of intestinal mucosa and activation and reduced colonic inflammatory cytokines in DSS-treated mice. Furthermore, Tanshinone IIA was demonstrated to significantly suppress neutrophil migration and activation. These results provide compelling evidence that Tanshinone IIA has a therapeutic potential for alleviating inflammatory colitis in mice, which is possibly mediated by the immunomodulation of neutrophils.

  14. IL-22+ CD4+ T cells are associated with therapeutic trichuris trichiura infection in an ulcerative colitis patient.

    Science.gov (United States)

    Broadhurst, Mara J; Leung, Jacqueline M; Kashyap, Vikram; McCune, Joseph M; Mahadevan, Uma; McKerrow, James H; Loke, P'ng

    2010-12-01

    Ulcerative colitis, a type of inflammatory bowel disease, is less common in countries endemic for helminth infections, suggesting that helminth colonization may have the potential to regulate intestinal inflammation in inflammatory bowel diseases. Indeed, therapeutic effects of experimental helminth infection have been reported in both animal models and clinical trials. Here, we provide a comprehensive cellular and molecular portrait of dynamic changes in the intestinal mucosa of an individual who infected himself with Trichuris trichiura to treat his symptoms of ulcerative colitis. Tissue with active colitis had a prominent population of mucosal T helper (T(H)) cells that produced the inflammatory cytokine interleukin-17 (IL-17) but not IL-22, a cytokine involved in mucosal healing. After helminth exposure, the disease went into remission, and IL-22-producing T(H) cells accumulated in the mucosa. Genes involved in carbohydrate and lipid metabolism were up-regulated in helminth-colonized tissue, whereas tissues with active colitis showed up-regulation of proinflammatory genes such as IL-17, IL-13RA2, and CHI3L1. Therefore, T. trichiura colonization of the intestine may reduce symptomatic colitis by promoting goblet cell hyperplasia and mucus production through T(H)2 cytokines and IL-22. Improved understanding of the physiological effects of helminth infection may lead to new therapies for inflammatory bowel diseases.

  15. Tolerogenic dendritic cells pulsed with enterobacterial extract suppress development of colitis in the severe combined immunodeficiency transfer model

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Gad, M; Kristensen, N N

    2007-01-01

    and experimental allergic encephalitis, but the effect in inflammatory bowel disease has not yet been demonstrated. In severe combined immunodeficient (SCID) mice, adoptively transferred CD4(+) CD25(-) T cells repopulate the lymphoid tissues and lead to development of chronic colitis characterized by CD4(+) T...

  16. Halofuginone reduces the inflammatory responses of DSS-induced colitis through metabolic reprogramming.

    Science.gov (United States)

    Liu, Jing; Xiao, Hai-Tao; Wang, Hong-Sheng; Mu, Huai-Xue; Zhao, Ling; Du, Jun; Yang, Depo; Wang, Dongmei; Bian, Zhao-Xiang; Lin, Shu-Hai

    2016-06-21

    Hypoxia and inflammation have been identified as the hallmarks of colitis, intertwined with metabolism. Here, we report that halofuginone (HF), an antiparasitic drug, attenuates dextran sulfate sodium (DSS)-induced colitis in mice, as represented by attenuating the disease activity index, inhibiting colonic shortening, ameliorating colonic lesions and histological signs of damage, reducing colonic myeloperoxidase activity, and suppressing the production of pro-inflammatory cytokines in colon tissue. Intriguingly, the hypoxia-inducible factor 1alpha (HIF-1α) and tumor necrosis factor alpha were also suppressed by HF treatment in colon tissues, exhibiting a tissue-specific effect. To further reveal the metabolic signatures upon HF treatment, mass spectrometry-based metabolomic analysis of the small molecular metabolites in liver, spleen and colon tissues was performed. As a result, we found that HF treatment counteracted the levels of acylcarnitines, including palmitoyl-l-carnitine, isobutyrylcarnitine, vaccenylcarnitine, and myristoylcarnitine, in colon tissues with DSS induction, but no significant change in the levels of acylcarnitines was observed in liver or spleen tissues. The metabolic signatures may indicate that incomplete fatty acid oxidation (FAO) in the colon could be restored upon HF treatment as the tissue-specific metabolic characterization. Taken together, our findings uncovered that the HF potentiated anti-inflammatory effect in DSS-induced colitis in mice and its underlying mechanisms could be associated with the inhibition of HIF-1α and reduced levels of acylcarnitines, suggesting that both the inhibition of HIF-1α and the counteraction of incomplete FAO might be useful in the prevention and treatment of inflammatory bowel disease.

  17. Regulatory T-cell depletion in the gut caused by integrin β7 deficiency exacerbates DSS colitis by evoking aberrant innate immunity.

    Science.gov (United States)

    Zhang, H L; Zheng, Y J; Pan, Y D; Xie, C; Sun, H; Zhang, Y H; Yuan, M Y; Song, B L; Chen, J F

    2016-03-01

    Integrin α4β7 controls lymphocyte trafficking into the gut and has essential roles in inflammatory bowel disease (IBD). The α4β7-blocking antibody vedolizumab is approved for IBD treatment; however, high dose of vedolizumab aggravates colitis in a small percentage of patients. Herein, we show that integrin β7 deficiency results in colonic regulatory T (Treg) cell depletion and exacerbates dextran sulfate sodium (DSS) colitis by evoking aberrant innate immunity. In DSS-treated β7-deficient mice, the loss of colonic Treg cells induces excessive macrophage infiltration in the colon via upregulation of colonic epithelial intercellular adhesion molecule 1 and increases proinflammatory cytokine expression, thereby exacerbating DSS-induced colitis. Moreover, reconstitution of the colonic Treg cell population in β7-deficient mice suppresses aberrant innate immune response in the colon and attenuates DSS colitis. Thus, integrin α4β7 is essential for suppression of DSS colitis as it regulates the colonic Treg cell population and innate immunity.

  18. Dextran sulfate sodium (DSS)-induced colitis in mice.

    Science.gov (United States)

    Chassaing, Benoit; Aitken, Jesse D; Malleshappa, Madhu; Vijay-Kumar, Matam

    2014-02-04

    Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis and Crohn's Disease, are complex and multifactorial diseases with unknown etiology. For the past 20 years, to study human IBD mechanistically, a number of murine models of colitis have been developed. These models are indispensable tools to decipher underlying mechanisms of IBD pathogenesis as well as to evaluate a number of potential therapeutics. Among various chemically induced colitis models, the dextran sulfate sodium (DSS)-induced colitis model is widely used because of its simplicity and many similarities with human ulcerative colitis. This model has both advantages and disadvantages that must be considered when employed. This protocol describes the DSS-induced colitis model, focusing on details and factors that could affect DSS-induced pathology.

  19. 饮食多不饱和脂肪酸ω-3/ω-6比值对小鼠实验性结肠炎的影响%Effects of the diet ratio of polyunsaturated fatty acids ω-3/ω-6 on experimental colitis in mice

    Institute of Scientific and Technical Information of China (English)

    田雨; 田玉玲; 李俊霞; 戴芸; 王化虹; 刘新光

    2013-01-01

    ) on dextran sulfate sodium ( DSS)-induced colitis in mice. Methods: Thirty-two male BALB/c mice were randomly divided into two groups: control group and PUFA group, PUFA group was continuously divided into 3 sub-groups: PUFA ω-3/ω-6 1: 3 group, PUFA ω-3/ω-6 1: 15 group and PUFA ω-3/Ω-6 1:30 group. According to the difference in the sub-groups, PUFA group mice were fed with the corresponding modified diet. The control group was fed with the common diet, whose ratio of PUFA ω-3/ω-6 was 1: 15. After eight weeks of different diets, experimental colitis in the three sub-groups of PUFA group was induced by DSS exposure. The mice were placed on three five-day cycles of 30 g/L DSS with ten days of recovery after each cycle, then were sacrificed after the final ten-day period. Overall symptomatic score and histopathological score were evaluated. And levels of mucosal prostaglandin E2 (PGE2) in the proximal and distal colon were measured respectively by enzyme immunoassay. Results: The changed ratio of PUFA ω-3/ω-6 had no effect on the weight gain of the growing mice. Although there were no significant differences among the PUFA groups from the three separate aspects; weight gain, stool character and blood in the stool, there were significant differences among the three groups in overall symptomatic scores. A further comparison showed the overall symptomatic score of 1: 3 group was significantly lower than that of the 1: 30 group (P <0. 05). There were significant differences among the PUFA groups in the histopathological score. The following comparison between the sub-groups showed the histopathologi- cal score of the 1:3 group was significantly lower than that of the 1:30 group (P < 0. 05). One mouse in the 1: 30 group died of severe hemorrhage and one mouse also in this group had a huge dysplastic adeno-matous polyp. The mucosal PGE2 which could reflect the level of intestinal inflammation showed that in the distal colon, the inflammations were obvious, and the

  20. Cytomegalovirus-associated colitis causing diarrhea in an immunocompetent patient

    Institute of Scientific and Technical Information of China (English)

    Dan Carter; David Olchovsky; Russell Pokroy; David Ezra

    2006-01-01

    Cytomegalovirus (CMV) colitis rarely occurs in immunocompetent patients. We report a case of disabling and life threatening diarrhea in an immunocompetent elderly woman due to CMV colitis. The diagnosis of CMV was based on histological examination of tissues biopsied at colonoscopy, positive CMV antigen and high CMV-IgM titer in peripheral blood samples and a good response to systemic gancyclovir treatment.We conclude that CMV should be considered in the differential diagnosis of colitis in elderly immunocompetent patients.

  1. Quercetin Isolated from Toona sinensis Leaves Attenuates Hyperglycemia and Protects Hepatocytes in High-Carbohydrate/High-Fat Diet and Alloxan Induced Experimental Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Yali Zhang

    2016-01-01

    Full Text Available The development of diabetes mellitus is related to oxidant stress induced by a high carbohydrate/high-fat diet (HFD. Quercetin, as a major bioactive component in Toona sinensis leaves (QTL, is a natural antioxidant. However, the exact mechanism by which QTL ameliorate diabetes mellitus is still unknown. In this study, we investigated the hypoglycemic effects and hepatocytes protection of QTL on HFD and alloxan induced diabetic mice. Intragastric administration of QTL significantly reduced body weight gain, serum glucose, insulin, total cholesterol, triglyceride, low density lipoprotein-cholesterol, alanine aminotransferase, and aspartate aminotransferase serum levels compared to those of diabetic mice. Furthermore, it significantly attenuated oxidative stress, as determined by lipid peroxidation, nitric oxide content, and inducible nitric oxide synthase activity and as a result attenuated liver injury. QTL also significantly suppressed the diabetes-induced activation of the p65/NF-κB and ERK1/2/MAPK pathways, as well as caspase-9 and caspase-3 levels in liver tissues of diabetic mice. Finally, micrograph analysis of liver samples showed decreased cellular organelle injury in hepatocytes of QTL treated mice. Taken together, QTL can be viewed as a promising dietary agent that can be used to reduce the risk of diabetes mellitus and its secondary complications by ameliorating oxidative stress in the liver.

  2. Cerebrolysin treatment attenuates heat shock protein overexpression in the brain following heat stress: an experimental study using immunohistochemistry at light and electron microscopy in the rat.

    Science.gov (United States)

    Sharma, Hari Shanker; Muresanu, Dafin; Sharma, Aruna; Zimmermann-Meinzingen, Sibilla

    2010-06-01

    The possibility that overexpression of heat shock proteins (HSPs) in the CNS represents a neurodestructive signal following hyperthermia was examined in a rat model using a potent neuroprotective drug, Cerebrolysin (Ebewe Pharma, Austria). Rats subjected to four hours of heat stress in a biological oxygen demand incubator at 38 degrees C developed profound hyperthermia (41.23 +/- 0.14 degrees C) and overexpressed HSP 72 kD in several brain regions: cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus, brain stem, and spinal cord compared to controls. This HSP overexpression closely correlated with the leakage of blood-brain barrier permeability and vasogenic edema formation in these brain areas. HSP positive cells are largely confined in the edematous brain regions showing Evans blue leakage. Pretreatment with Cerebrolysin (5 mL/kg, i.v.) 30 minutes before heat stress markedly attenuated hyperthermia (39.48 +/- 0.23 degrees C, P Cerebrolysin pretreatment. These results are the first to show that Cerebrolysin, if administered before heat stress, attenuates hyperthermia induced stress reaction and HSP 72 kD induction. Taken together, these novel observations suggest that upregulation of HSP 72 kD in brain represents neurodestructive signals and a reduction in cellular stress mechanisms leading to decline in HSP expression is neuroprotective in nature.

  3. Chronic Administration of Oil Palm (Elaeis guineensis Leaves Extract Attenuates Hyperglycaemic-Induced Oxidative Stress and Improves Renal Histopathology and Function in Experimental Diabetes

    Directory of Open Access Journals (Sweden)

    Varatharajan Rajavel

    2012-01-01

    Full Text Available Oil palm (Elaeis guineensis leaves extract (OPLE has antioxidant properties and because oxidative stress contributes to the pathogenesis of diabetic nephropathy (DN, we tested the hypothesis that OPLE prevents diabetes renal oxidative stress, attenuating injury. Sprague-Dawley rats received OPLE (200 and 500 mg kg−1 for 4 and 12 weeks after diabetes induction (streptozotocin 60 mg kg−1. Blood glucose level, body and kidney weights, urine flow rate (UFR, glomerular filtration rate (GFR, and proteinuria were assessed. Oxidative stress variables such as 8-hydroxy-2′-deoxyguanosine (8-OHdG, glutathione (GSH, and lipid peroxides (LPO were quantified. Renal morphology was analysed, and plasma transforming growth factor-beta1 (TGF-β1 was measured. Diabetic rats demonstrated increase in blood glucose and decreased body and increased kidney weights. Renal dysfunction (proteinuria, elevations in UFR and GFR was observed in association with increases in LPO, 8-OHdG, and TGF-β1 and a decrease in GSH. Histological evaluation of diabetic kidney demonstrated glomerulosclerosis and tubulointerstitial fibrosis. OPLE attenuated renal dysfunction, improved oxidative stress markers, and reduced renal pathology in diabetic animals. These results suggest OPLE improves renal dysfunction and pathology in diabetes by reducing oxidative stress; furthermore, the protective effect of OPLE against renal damage in diabetes depends on the dose of OPLE as well as progression of DN.

  4. Pseudomembranous Colitis: Not Always Caused by Clostridium difficile.

    Science.gov (United States)

    Tang, Derek M; Urrunaga, Nathalie H; De Groot, Hannah; von Rosenvinge, Erik C; Xie, Guofeng; Ghazi, Leyla J

    2014-01-01

    Although classically pseudomembranous colitis is caused by Clostridium difficile, it can result from several etiologies. Certain medications, chemical injury, collagenous colitis, inflammatory bowel disease, ischemia, and other infectious pathogens can reportedly cause mucosal injury and subsequent pseudomembrane formation. We present the case of a middle-aged woman with vascular disease who was incorrectly diagnosed with refractory C. difficile infection due to the presence of pseudomembranes. Further imaging, endoscopy, and careful histopathology review revealed chronic ischemia as the cause of her pseudomembranous colitis and diarrhea. This case highlights the need for gastroenterologists to consider non-C. difficile etiologies when diagnosing pseudomembranous colitis.

  5. Ulcerative colitis six years after colon cancer: only a coincidence?

    Science.gov (United States)

    Sakellakis, Minas; Makatsoris, Thomas; Gkermpesi, Maria; Peroukidis, Stavros; Kalofonos, Haralabos

    2014-01-01

    The association between inflammatory bowel disease and colorectal cancer is well known. Ulcerative colitis is a risk factor for the development of colorectal cancer, and this risk increases with the activity and duration of bowel inflammation. Here we describe the case of a 52-year-old man who developed ulcerative colitis 6 years after the diagnosis and treatment of colon cancer. Although this could be a coincidence, there could be additional possibilities, like pre-existence of quiescent colitis, late effect of therapy, or maybe the existence of common pathogenetic factors contributing to the development of ulcerative colitis and colorectal cancer. PMID:24855393

  6. Pseudomembranous Colitis: Not Always Caused by Clostridium difficile

    Directory of Open Access Journals (Sweden)

    Derek M. Tang

    2014-01-01

    Full Text Available Although classically pseudomembranous colitis is caused by Clostridium difficile, it can result from several etiologies. Certain medications, chemical injury, collagenous colitis, inflammatory bowel disease, ischemia, and other infectious pathogens can reportedly cause mucosal injury and subsequent pseudomembrane formation. We present the case of a middle-aged woman with vascular disease who was incorrectly diagnosed with refractory C. difficile infection due to the presence of pseudomembranes. Further imaging, endoscopy, and careful histopathology review revealed chronic ischemia as the cause of her pseudomembranous colitis and diarrhea. This case highlights the need for gastroenterologists to consider non-C. difficile etiologies when diagnosing pseudomembranous colitis.

  7. Current Status of the Treatment of Fulminant Colitis.

    Science.gov (United States)

    Ferrer Márquez, Manuel; Hernández Martínez, Álvaro; Reina Duarte, Ángel; Rosado Cobián, Rafael

    2015-05-01

    Fulminant colitis is not a well-defined entity, that constitutes a severe complication. It usually occurs in the course of úlcerative colitis and Clostridium difficile colitis. A multidisciplinary management combining gastroenterologist and surgeons is crucial with intensive medical treatment and early surgery in non-responders. It is important to distinguish if we are facing a flare of IBD or, on the contrary, it is an infectious colitis, due to the fact that although general therapeutic measures to adopt will be the same, they will demand opposed specific measures.