Excretory/secretory products from Trichinella spiralis adult worms ameliorate DSS-induced colitis in mice.

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Xiaodi Yang

Full Text Available BACKGROUND: Many evidences show the inverse correlation between helminth infection and allergic or autoimmune diseases. Identification and characterization of the active helminth-derived products responsible for the beneficial effects on allergic or inflammatory diseases will provide another feasible approach to treat these diseases. METHODS AND FINDINGS: Colitis was induced in C57BL/6 mice by giving 3% DSS orally for 7 days. During this period, the mice were treated daily with the excretory/secretory products from T. spiralis adult worms (AES intraperitoneally. The severity of colitis was monitored by measuring body weight, stool consistency or bleeding, colon length and inflammation. To determine the T. spiralis AES product-induced immunological response, Th1, Th2, Th17 and regulatory cytokine profiles were measured in lymphocytes isolated from colon, mesenteric lymph nodes (MLN, and the spleen of treated mice. The CD4+ CD25+ FOXP3+ regulatory T cells (Tregs were also measured in the spleens and MLN of treated mice. Mice treated with AES significantly ameliorated the severity of the DSS-induced colitis indicated by the reduced disease manifestations, improved macroscopic and microscopic inflammation correlated with the up-regulation of Treg response (increased regulatory cytokines IL-10, TGF-beta and regulatory T cells and down-regulation of pro-inflammatory cytokines (IFN-gamma, IL-6 and IL-17 in the spleens, MLN and colon of treated mice. CONCLUSIONS: Our results provide direct evidences that T. spiralis AES have a therapeutic potential for alleviating inflammatory colitis in mice. This effect is possibly mediated by the immunomodulation of regulatory T cells to produce regulatory and anti-inflammatory cytokines and inhibit pro-inflammatory cytokines.

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

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

2015-11-06

To evaluate the effect of orally administered plecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models. The cyclic guanosine monophosphate (cGMP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cell-based 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. 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 cGMP-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. This is the first-ever study reporting

Hydrogen peroxide increases depolarization-induced contraction of mechanically skinned slow twitch fibres from rat skeletal muscles.

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Plant, David R; Lynch, Gordon S; Williams, David A

2002-03-15

The effect of exogenous hydrogen peroxide (H(2)O(2)) on excitation-contraction (E-C) coupling and sarcoplasmic reticulum (SR) function was compared in mechanically skinned slow twitch fibres (prepared from the soleus muscles) and fast twitch fibres (prepared from the extensor digitorum longus; EDL muscles) of adult rats. Equilibration (5 min) with 1 mM H(2)O(2) diminished the ability of the Ca(2+)-depleted SR to reload Ca(2+) in both slow (P fast twitch fibres (P fast twitch fibres by 24 +/- 5 % (P slow twitch fibres. Treatment with 1 mM H(2)O(2) also increased the peak force of low [caffeine] contracture by approximately 45% in both fibre types compared to control (P slow twitch fibres, compared to control (no H(2)O(2); P fast twitch fibres was not altered by 1 mM H(2)O(2) treatment. Equilibration with 5 mM H(2)O(2) induced a spontaneous force response in both slow and fast twitch fibres, which could be partly reversed by 2 min treatment with 10 mM DTT. Peak DICR was also increased approximately 40% by 5 mM H(2)O(2) in slow twitch fibres compared to control (no H(2)O(2); P slow but not fast twitch fibres. The increase in depolarization-induced contraction in slow twitch fibres might be mediated by an increased SR Ca(2+) release during contraction and/or an increase in Ca(2+) sensitivity.

Antagonizing Arachidonic Acid-Derived Eicosanoids Reduces Inflammatory Th17 and Th1 Cell-Mediated Inflammation and Colitis Severity

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Jennifer M. Monk

2014-01-01

Full Text Available During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA- derived eicosanoids, such as prostaglandin E2 (PGE2, promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS- induced colitis. Fat-1 mice contain the ω3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Δ5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORγτ, and IL-23, decreased percentages of Th17 cells and, improved colon injury scores (P≤0.05. Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.

Bacillus Coagulans GBI-30 (BC30 improves indices of Clostridium difficile-Induced colitis in mice

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Fitzpatrick Leo R

2011-10-01

Full Text Available Abstract Background Probiotics have beneficial effects in rodent models of Clostridium difficile (C. diffiicle-induced colitis. The spore forming probiotic strain Bacillus Coagulans GBI-30, 6086 (BC30 has demonstrated anti-inflammatory and immune-modulating effects in vitro. Our goal was to determine if BC30 improved C. difficile-induced colitis in mice. Starting on study day 0, female C57BL/6 mice were dosed by oro-gastric gavage for 15 days with vehicle (saline or BC30 (2 × 109 CFU per day. Mice in the C. difficile groups received an antibiotic mixture (study days 5 to 8 in the drinking water, and clindamycin (10 mg/kg, i.p., on study day 10. The C. difficile strain VPI 10463 was given by gavage at 104 CFU to induce colitis on day 11. On day 16, stools and colons were collected for further analyses. Results All mice treated with BC30 survived on study day 13, while two mice treated with vehicle did not survive. On day 12, a significant difference (p = 0.0002 in the percentage of mice with normal stools (66.7% was found in the BC30/C. difficile group, as compared to the vehicle/C. diffcile group (13.0%. On study day 16, 23.8% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0187. On this day, the stool consistency score for the BC30/C. difficile group (1.1 ± 0.2 was significantly lower (p C. difficile cohort (1.9 ± 0.2. BC30 modestly attenuated the colonic pathology (crypt damage, edema, leukocyte influx that was present following C. difficile infection. Colonic MIP-2 chemokine contents (pg/2 cm colon were: 10.2 ± 0.5 (vehicle/no C. difficile, 24.6 ± 9.5 (vehicle/C. difficile and 16.3 ± 4.3 (BC30/C. difficle. Conclusion The probiotic BC30 improved some parameters of C. difficile-induced colitis in mice. BC30 prolonged the survival of C. diffiicle infected mice. Particularly, this probiotic improved the stool consistency of mice, in this infectious colitis model.

Bacillus Coagulans GBI-30 (BC30) improves indices of Clostridium difficile-Induced colitis in mice

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2011-01-01

Background Probiotics have beneficial effects in rodent models of Clostridium difficile (C. diffiicle)-induced colitis. The spore forming probiotic strain Bacillus Coagulans GBI-30, 6086 (BC30) has demonstrated anti-inflammatory and immune-modulating effects in vitro. Our goal was to determine if BC30 improved C. difficile-induced colitis in mice. Starting on study day 0, female C57BL/6 mice were dosed by oro-gastric gavage for 15 days with vehicle (saline) or BC30 (2 × 109 CFU per day). Mice in the C. difficile groups received an antibiotic mixture (study days 5 to 8 in the drinking water), and clindamycin (10 mg/kg, i.p., on study day 10). The C. difficile strain VPI 10463 was given by gavage at 104 CFU to induce colitis on day 11. On day 16, stools and colons were collected for further analyses. Results All mice treated with BC30 survived on study day 13, while two mice treated with vehicle did not survive. On day 12, a significant difference (p = 0.0002) in the percentage of mice with normal stools (66.7%) was found in the BC30/C. difficile group, as compared to the vehicle/C. diffcile group (13.0%). On study day 16, 23.8% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0187). On this day, the stool consistency score for the BC30/C. difficile group (1.1 ± 0.2) was significantly lower (p < 0.05) than for the vehicle/C. difficile cohort (1.9 ± 0.2). BC30 modestly attenuated the colonic pathology (crypt damage, edema, leukocyte influx) that was present following C. difficile infection. Colonic MIP-2 chemokine contents (pg/2 cm colon) were: 10.2 ± 0.5 (vehicle/no C. difficile), 24.6 ± 9.5 (vehicle/C. difficile) and 16.3 ± 4.3 (BC30/C. difficle). Conclusion The probiotic BC30 improved some parameters of C. difficile-induced colitis in mice. BC30 prolonged the survival of C. diffiicle infected mice. Particularly, this probiotic improved the stool consistency of mice, in this infectious colitis model. PMID

Cell-mediated fibre recruitment drives extracellular matrix mechanosensing in engineered fibrillar microenvironments

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Baker, Brendon M.; Trappmann, Britta; Wang, William Y.; Sakar, Mahmut S.; Kim, Iris L.; Shenoy, Vivek B.; Burdick, Jason A.; Chen, Christopher S.

2015-12-01

To investigate how cells sense stiffness in settings structurally similar to native extracellular matrices, we designed a synthetic fibrous material with tunable mechanics and user-defined architecture. In contrast to flat hydrogel surfaces, these fibrous materials recapitulated cell-matrix interactions observed with collagen matrices including stellate cell morphologies, cell-mediated realignment of fibres, and bulk contraction of the material. Increasing the stiffness of flat hydrogel surfaces induced mesenchymal stem cell spreading and proliferation; however, increasing fibre stiffness instead suppressed spreading and proliferation for certain network architectures. Lower fibre stiffness permitted active cellular forces to recruit nearby fibres, dynamically increasing ligand density at the cell surface and promoting the formation of focal adhesions and related signalling. These studies demonstrate a departure from the well-described relationship between material stiffness and spreading established with hydrogel surfaces, and introduce fibre recruitment as a previously undescribed mechanism by which cells probe and respond to mechanics in fibrillar matrices.

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

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Zheng, Bin; van Bergenhenegouwen, Jeroen; Overbeek, Saskia; van de Kant, Hendrik J G; Garssen, Johan; Folkerts, Gert; Vos, Paul; Morgan, Mary E; Kraneveld, Aletta D

2014-01-01

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.

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.

Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice

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Fitzpatrick, Leo R; Small, Jeffrey S; Greene, Wallace H; Karpa, Kelly D; Farmer, Sean; Keller, David

2012-01-01

Abstract Background Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 104...

Slc5a8, a Na+-coupled high-affinity transporter for short-chain fatty acids, is a conditional tumour suppressor in colon that protects against colitis and colon cancer under low-fibre dietary conditions.

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Gurav, Ashish; Sivaprakasam, Sathish; Bhutia, Yangzom D; Boettger, Thomas; Singh, Nagendra; Ganapathy, Vadivel

2015-07-15

Mammalian colon harbours trillions of bacteria under physiological conditions; this symbiosis is made possible because of a tolerized response from the mucosal immune system. The mechanisms underlying this tolerogenic phenomenon remain poorly understood. In the present study we show that Slc5a8 (solute carrier gene family 5a, member 8), a Na(+)-coupled high-affinity transporter in colon for the bacterial fermentation product butyrate, plays a critical role in this process. Among various immune cells in colon, dendritic cells (DCs) are unique not only in their accessibility to luminal contents but also in their ability to induce tolerogenic phenotype in T-cells. We found that DCs exposed to butyrate express the immunosuppressive enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and aldehyde dehydrogenase 1A2 (Aldh1A2), promote conversion of naive T-cells into immunosuppressive forkhead box P3(+) (FoxP3(+)) Tregs (regulatory T-cells) and suppress conversion of naive T-cells into pro-inflammatory interferon (IFN)-γ-producing cells. Slc5a8-null DCs do not induce IDO1 and Aldh1A2 and do not generate Tregs or suppress IFN-γ-producing T-cells in response to butyrate. We also provide in vivo evidence for an obligatory role for Slc5a8 in suppression of IFN-γ-producing T-cells. Furthermore, Slc5a8 protects against colitis and colon cancer under conditions of low-fibre intake but not when dietary fibre intake is optimal. This agrees with the high-affinity nature of the transporter to mediate butyrate entry into cells. We conclude that Slc5a8 is an obligatory link between dietary fibre and mucosal immune system via the bacterial metabolite butyrate and that this transporter is a conditional tumour suppressor in colon linked to dietary fibre content. © 2015 Authors; published by Portland Press Limited.

IL10-Deficiency in CD4+ T Cells Exacerbates the IFNγ and IL17 Response During Bacteria Induced Colitis

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Virginia Seiffart

2015-07-01

Full Text Available Background/Aims: IL10 is a key inhibitor of effector T cell activation and a mediator of intestinal homeostasis. In addition, IL10 has emerged as a key immunoregulator during infection with various pathogens, ameliorating the excessive T-cell responses that are responsible for much of the immunopathology associated with the infection. Because IL10 plays an important role in both intestinal homeostasis and infection, we studied the function of IL10 in infection-associated intestinal inflammation. Methods: Wildtype mice and mice deficient in CD4+ T cell-derived or regulatory T cells-derived IL10 were infected with the enteric pathogen Citrobacter (C. rodentium and analyzed for the specific immune response and pathogloy in the colon. Results: We found that IL10 expression is upregulated in colonic tissue after infection with C. rodentium, especially in CD4+ T cells, macrophages and dendritic cells. Whereas the deletion of IL10 in regulatory T cells had no effect on C. rodentium induced colitis, infection of mice deficient in CD4+ T cell-derived IL10 exhibited faster clearance of the bacterial burden but worse colitis, crypt hyperplasia, and pathology than did WT mice. In addition, the depletion of CD4+ T cell-derived IL10 in infected animals was accompanied by an accelerated IFNγ and IL17 response in the colon. Conclusion: Thus, we conclude that CD4+ T cell-derived IL10 is strongly involved in the control of C. rodentium-induced colitis. Interference with this network could have implications for the treatment of infection-associated intestinal inflammation.

Chickpea supplementation prior to colitis onset reduces inflammation in dextran sodium sulfate-treated C57Bl/6 male mice.

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Monk, Jennifer M; Wu, Wenqing; McGillis, Laurel H; Wellings, Hannah R; Hutchinson, Amber L; Liddle, Danyelle M; Graf, Daniela; Robinson, Lindsay E; Power, Krista A

2018-03-09

The potential for a chickpea supplemented diet (rich in fermentable non-digestible carbohydrates and phenolic compounds) to modify the colonic microenvironment and attenuate the severity of acute colonic inflammation was investigated. C57Bl/6 male mice were fed a control basal diet (BD) or BD supplemented with 20% cooked chickpea flour for 3 weeks prior to acute colitis onset induced by 7-day exposure to dextran sodium sulfate (DSS, 2% w/v in drinking water) and colon and serum levels of inflammatory mediators were assessed. Despite an equal degree of DSS-induced epithelial barrier histological damage and clinical symptoms between dietary groups, biomarkers of the ensuing inflammatory response were attenuated by CK pre-feeding including reduced colon tissue activation of NFκB and inflammatory cytokine production (TNFα and IL-18). Additionally, colon protein expression of anti-inflammatory (IL-10) and epithelial repair (IL-22 and IL-27) cytokines were increased by CK pre-feeding. Furthermore, during acute colitis CK pre-feeding increased markers of enhanced colonic function including mRNA expression of Relmβ and IgA. Collectively, CK pre-feeding modulated the baseline function of the colonic microenvironment, whereby upon induction of acute colitis, the severity of the inflammatory response was attenuated.

Determination of material properties for short fibre reinforced C/C-SiC

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Hausherr J.-M.

2015-01-01

Full Text Available Determining the mechanical properties of short fibre reinforced CMC using standard sized coupons has always been a challenge due to a high statistical scattering of the measured values. Although the random orientation of short fibres results in a quasi-isotropic material behavior of 2D-structures with a sufficiently large volume, the small volume typical for test coupons usually results in a non-isotropic fibre orientation in the tested volume. This paper describes a method for manufacturing unidirectional oriented short fibre reinforced CMC materials and presents material properties of UD-C/C-SiC. After verifying the fibre orientation of the CMC using micro-computed tomography, coupons were extracted to determine the orthotropic material properties. These orthotropic material properties were then used to predict the properties of C/C-SiC with randomly distributed short fibres. To validate the method, micro-computed tomography is used to quantitatively determine the fibre orientation within coupons extracted from randomly distributed short fibre C/C-SiC. After mechanical three-point-bending tests, the measured stiffness and bending strength is compared with the predicted properties. Finally, the data are used to devise a method suited for reducing the inherent large spread of material properties associated with the measurement of CMC materials with randomly distributed short fibres.

Interferon-γ induces expression of MHC class II on intestinal epithelial cells and protects mice from colitis.

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Christoph Thelemann

Full Text Available Immune responses against intestinal microbiota contribute to the pathogenesis of inflammatory bowel diseases (IBD and involve CD4(+ T cells, which are activated by major histocompatibility complex class II (MHCII molecules on antigen-presenting cells (APCs. However, it is largely unexplored how inflammation-induced MHCII expression by intestinal epithelial cells (IEC affects CD4(+ T cell-mediated immunity or tolerance induction in vivo. Here, we investigated how epithelial MHCII expression is induced and how a deficiency in inducible epithelial MHCII expression alters susceptibility to colitis and the outcome of colon-specific immune responses. Colitis was induced in mice that lacked inducible expression of MHCII molecules on all nonhematopoietic cells, or specifically on IECs, by continuous infection with Helicobacter hepaticus and administration of interleukin (IL-10 receptor-blocking antibodies (anti-IL10R mAb. To assess the role of interferon (IFN-γ in inducing epithelial MHCII expression, the T cell adoptive transfer model of colitis was used. Abrogation of MHCII expression by nonhematopoietic cells or IECs induces colitis associated with increased colonic frequencies of innate immune cells and expression of proinflammatory cytokines. CD4(+ T-helper type (Th1 cells - but not group 3 innate lymphoid cells (ILCs or Th17 cells - are elevated, resulting in an unfavourably altered ratio between CD4(+ T cells and forkhead box P3 (FoxP3(+ regulatory T (Treg cells. IFN-γ produced mainly by CD4(+ T cells is required to upregulate MHCII expression by IECs. These results suggest that, in addition to its proinflammatory roles, IFN-γ exerts a critical anti-inflammatory function in the intestine which protects against colitis by inducing MHCII expression on IECs. This may explain the failure of anti-IFN-γ treatment to induce remission in IBD patients, despite the association of elevated IFN-γ and IBD.

The majority of lamina propria CD4(+) T-cells from scid mice with colitis undergo Fas-mediated apoptosis in vivo

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Bregenholt, S; Petersen, T R; Claesson, Mogens Helweg

2001-01-01

We have previously shown that adoptively transferred CD4(+) T-cells mediate an chronic colitis in severe combined immune deficient (scid) mice. Colitis is accompanied by activation and apoptosis of Fas ligand and TNF-alpha expressing CD4(+) T-cells in the diseased colonic lamina propria (Eur. J....... Immunol. 28:3655 (1998)). Here we investigate the apoptosis-inducing mechanism in these lamina propria infiltrating CD4(+) T-cells. We observe that freshly isolated lamina propria CD4(+) T-cells can kill Fas transfected P815 mastocytoma cells in a TCR/CD3 redirected chromium-release assay, but do...... not express TNF-alpha mediated cytotoxicity. Pre-incubation of the isolated lamina propria CD4(+) T-cells with an anti-FasL antiserum partially blocked killing of the Fas transfected target cells, indicating a role for the Fas-FasL system in the killing process. Treatment of scid mice with colitis with anti-Fas...

Acute nonsteroidal anti-inflammatory drug-induced colitis

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Massimo Tonolini

2013-01-01

Full Text Available Resulting from direct toxicity on the bowel mucosa, nonsteroidal anti-inflammatory drug (NSAID-induced colitis is an underestimated although potentially serious condition. Plain abdominal radiographs and multidetector computed tomography allow to identify a right-sided acute colitis with associated pericolonic inflammation, progressively diminished changes along the descending and sigmoid colon, and rectal sparing, consistent with the hypothesized pathogenesis of NSAID colitis. Increased awareness of this condition should reduce morbidity through both prevention and early recognition. High clinical suspicion and appropriate patient questioning, together with consistent instrumental findings, negative biochemistry, and stool investigations should help physicians not to miss this important diagnosis.

Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

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Aleksandra Matuszyk

2016-01-01

Full Text Available Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

Fibroblast Growth Factor 21 Deficiency Attenuates Experimental Colitis-Induced Adipose Tissue Lipolysis

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Liming Liu

2017-01-01

Full Text Available Aims. Nutrient deficiencies are common in patients with inflammatory bowel disease (IBD. Adipose tissue plays a critical role in regulating energy balance. Fibroblast growth factor 21 (FGF21 is an important endocrine metabolic regulator with emerging beneficial roles in lipid homeostasis. We investigated the impact of FGF21 in experimental colitis-induced epididymal white adipose tissue (eWAT lipolysis. Methods. Mice were given 2.5% dextran sulfate sodium (DSS ad libitum for 7 days to induce colitis. The role of FGF21 was investigated using antibody neutralization or knockout (KO mice. Lipolysis index and adipose lipolytic enzymes were determined. In addition, 3T3-L1 cells were pretreated with IL-6, followed by recombinant human FGF21 (rhFGF21 treatment; lipolysis was assessed. Results. DSS markedly decreased eWAT/body weight ratio and increased serum concentrations of free fatty acid (FFA and glycerol, indicating increased adipose tissue lipolysis. eWAT intracellular lipolytic enzyme expression/activation was significantly increased. These alterations were significantly attenuated in FGF21 KO mice and by circulating FGF21 neutralization. Moreover, DSS treatment markedly increased serum IL-6 and FGF21 levels. IL-6 pretreatment was necessary for the stimulatory effect of FGF21 on adipose lipolysis in 3T3-L1 cells. Conclusions. Our results demonstrate that experimental colitis induces eWAT lipolysis via an IL-6/FGF21-mediated signaling pathway.

Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice

Science.gov (United States)

2012-01-01

Background Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 10463 was given by oro-gastric gavage at ≈ 5x104 CFU to induce colitis. Mice were treated on study days 6 to 10 with vancomycin (50 mg/kg) (vanco) or vehicle (saline) by gavage. On days 10 to16, mice were dosed by gavage with saline vehicle or BC30 (2 x 109 CFU per day). Mice were monitored for mortality, weight loss and diarrhea. On study days 14, 16 and 17, stools and colons were collected for analyzing other parameters of colitis. Results The mean stool consistency score in Vehicle/C.difficile/Vanco mice increased from 0.4 (day 10) to a range of 1.1 to 1.4 (days 14 to 17), indicating the recurrence of colitis. On days 13 through 17, the stool consistency scores for the vancomycin/BC30 mice were significantly lower (p< 0.05) than for the vancomycin/vehicle cohort of animals. On day 17, 88.9% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0004). Colonic myeloperoxidase (Units/2 cm colon) was significantly (p < 0.05) reduced from 4.3 ± 0.7 (Vehicle/C.difficile/Vanco) to 2.6 ± 0.2 (BC30/C. Difficle/Vanco). The colonic histology score and Keratinocyte derived-chemokine level in the colon were also lower in BC30 treated mice. Summary In BC30-treated mice, there was evidence of better stool consistency, as well as improved biochemical and histological indices of colitis, following initial treatment of animals with vancomycin. Conclusion BC30 limited the recurrence of CD-induced colitis following vancomycin withdrawal in mice. PMID

Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice.

Science.gov (United States)

Fitzpatrick, Leo R; Small, Jeffrey S; Greene, Wallace H; Karpa, Kelly D; Farmer, Sean; Keller, David

2012-10-22

Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 10463 was given by oro-gastric gavage at ≈ 5x104 CFU to induce colitis. Mice were treated on study days 6 to 10 with vancomycin (50 mg/kg) (vanco) or vehicle (saline) by gavage. On days 10 to16, mice were dosed by gavage with saline vehicle or BC30 (2 x 109 CFU per day). Mice were monitored for mortality, weight loss and diarrhea. On study days 14, 16 and 17, stools and colons were collected for analyzing other parameters of colitis. The mean stool consistency score in Vehicle/C.difficile/Vanco mice increased from 0.4 (day 10) to a range of 1.1 to 1.4 (days 14 to 17), indicating the recurrence of colitis. On days 13 through 17, the stool consistency scores for the vancomycin/BC30 mice were significantly lower (p< 0.05) than for the vancomycin/vehicle cohort of animals. On day 17, 88.9% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0004). Colonic myeloperoxidase (Units/2 cm colon) was significantly (p < 0.05) reduced from 4.3 ± 0.7 (Vehicle/C.difficile/Vanco) to 2.6 ± 0.2 (BC30/C. Difficle/Vanco). The colonic histology score and Keratinocyte derived-chemokine level in the colon were also lower in BC30 treated mice. In BC30-treated mice, there was evidence of better stool consistency, as well as improved biochemical and histological indices of colitis, following initial treatment of animals with vancomycin. BC30 limited the recurrence of CD-induced colitis following vancomycin withdrawal in mice.

Repeated Predictable Stress Causes Resilience against Colitis-Induced Behavioral Changes in Mice

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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.

Sonographic and Endoscopic Findings in Cocaine-Induced Ischemic Colitis

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Leth, Thomas; Wilkens, Rune; Bonderup, Ole Kristian

2015-01-01

Cocaine-induced ischemic colitis is a recognized entity. The diagnosis is based on clinical and endoscopic findings. However, diagnostic imaging is helpful in the evaluation of abdominal symptoms and prior studies have suggested specific sonographic findings in ischemic colitis. We report...

Inciting and etiologic agents of colitis.

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Silva, J; Fekety, R; Werk, C; Ebright, J; Cudmore, M; Batts, D; Syrjamaki, C; Lukens, J

1984-01-01

Since 1979, 3,115 stool samples were tested for detection of Clostridium difficile and its cytotoxin; these were obtained from patients who had drug-related diarrhea. Presumed or proven colitis due to C. difficile was diagnosed in 130 patients. Drugs implicated most commonly as causing or associated with the onset of enterocolitis due to C. difficile were ampicillin (38 episodes), cephalosporins (71), clindamycin (36), and the aminoglycosides (45). The hamster model of colitis was employed to explore the role of other inducing agents. Altering the usual diet of hamsters to one with a higher protein content decreased the time to death due to C. difficile cecitis following the administration of cefazolin (10 mg). Several cathartics also were studied for their effect on the lethality of antibiotic-induced cecitis. Daily administrations of castor oil (0.5 ml per day) and vegetable oil (1.0 ml per day) improved survival against lethal doses of clindamycin. Milk of magnesia or mineral oil provided no protection. Four patients with C. difficile colitis induced by therapy with cytotoxic drugs also were identified. Methotrexate induced cecitis when administered orally and daily to hamsters, and C. difficile and its cytotoxin were identified in the hamsters' stools. Death due to methotrexate-induced cecitis was prevented by daily administration of folinic acid or vancomycin. These data demonstrate that a variety of antibiotics, antineoplastic agents, cathartics, and diet changes can induce C. difficile colitis in humans and hamsters.

Somatostatin does not attenuate intestinal injury in dextran sodium sulphate-induced subacute colitis

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J. D. van Bergeijk

1998-01-01

Full Text Available From several in vitro and in vivo studies involvement of som atostatin (SMS in intestinal inflammation emerge. Acute colitis induced in rats is attenuated by the long-acting SMS analogue octreotide. We studied the potential beneficial effect of SMS on non-acute experimental colitis. BALB/c mice received either saline, SMS-14 (36 or 120 μg daily or octreotide (3 μg daily subcutaneously delivered by implant osmotic pumps. A non-acute colitis was induced by administration of dextran sodium sulphate (DSS 10% in drinking water during 7 days. DSS evoked a mild, superficial pancolitis, most characterized by mucosal ulceration and submucosal influx of neutrophils. Neither SMS-14 nor octreotide reduced mucosal inflammatory score or macroscopical disease activity, although reduction of intestinal levels of interleukin1 β (IL-1 β, IL-6 and IL-10 during DSS was augmented both by SMS and octreotide. A slight increase of neutrophil influx was seen during SMS administration in animals not exposed to DSS. In conclusion, SMS or its long-acting analogue did not reduce intestinal inflammation in non-acute DSS-induced colitis. According to the cytokine profile observed, SMS-14 and octreotide further diminished the reduction of intestinal macrophage and Th2 lymphocyte activity.

Bacillus Coagulans GBI-30 (BC30) improves indices of Clostridium difficile-Induced colitis in mice

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Fitzpatrick Leo R; Small Jeffrey S; Greene Wallace H; Karpa Kelly D; Keller David

2011-01-01

Abstract Background Probiotics have beneficial effects in rodent models of Clostridium difficile (C. diffiicle)-induced colitis. The spore forming probiotic strain Bacillus Coagulans GBI-30, 6086 (BC30) has demonstrated anti-inflammatory and immune-modulating effects in vitro. Our goal was to determine if BC30 improved C. difficile-induced colitis in mice. Starting on study day 0, female C57BL/6 mice were dosed by oro-gastric gavage for 15 days with vehicle (saline) or BC30 (2 × 109 CFU per d...

Effect of vitamin C on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated early colon cancer in mice.

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Jeon, Hee-Jin; Yeom, Yiseul; Kim, Yoo-Sun; Kim, Eunju; Shin, Jae-Ho; Seok, Pu Reum; Woo, Moon Jea; Kim, Yuri

2018-04-01

The objective of this study was to investigate the effects of vitamin C on inflammation, tumor development, and dysbiosis of intestinal microbiota in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced inflammation-associated early colon cancer mouse model. Male BALB/c mice were injected intraperitoneally with AOM [10 mg/kg body weight (b.w)] and given two 7-d cycles of 2% DSS drinking water with a 14 d inter-cycle interval. Vitamin C (60 mg/kg b.w. and 120 mg/kg b.w.) was supplemented by gavage for 5 weeks starting 2 d after the AOM injection. The vitamin C treatment suppressed inflammatory morbidity, as reflected by disease activity index (DAI) in recovery phase and inhibited shortening of the colon, and reduced histological damage. In addition, vitamin C supplementation suppressed mRNA levels of pro-inflammatory mediators and cytokines, including cyclooxygenase-2, microsomal prostaglandin E synthase-2, tumor necrosis factor-α, Interleukin (IL)-1β , and IL-6 , and reduced expression of the proliferation marker, proliferating cell nuclear antigen, compared to observations of AOM/DSS animals. Although the microbial composition did not differ significantly between the groups, administration of vitamin C improved the level of inflammation-related Lactococcus and JQ084893 to control levels. Vitamin C treatment provided moderate suppression of inflammation, proliferation, and certain inflammation-related dysbiosis in a murine model of colitis associated-early colon cancer. These findings support that vitamin C supplementation can benefit colonic health. Long-term clinical studies with various doses of vitamin C are warranted.

MicroRNA214 Is Associated With Progression of Ulcerative Colitis, and Inhibition Reduces Development of Colitis and Colitis-Associated Cancer in Mice.

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Polytarchou, Christos; Hommes, Daniel W; Palumbo, Tiziana; Hatziapostolou, Maria; Koutsioumpa, Marina; Koukos, Georgios; van der Meulen-de Jong, Andrea E; Oikonomopoulos, Angelos; van Deen, Welmoed K; Vorvis, Christina; Serebrennikova, Oksana B; Birli, Eleni; Choi, Jennifer; Chang, Lin; Anton, Peter A; Tsichlis, Philip N; Pothoulakis, Charalabos; Verspaget, Hein W; Iliopoulos, Dimitrios

2015-10-01

Persistent activation of the inflammatory response contributes to the development of inflammatory bowel diseases, which increase the risk of colorectal cancer. We aimed to identify microRNAs that regulate inflammation during the development of ulcerative colitis (UC) and progression to colitis-associated colon cancer (CAC). We performed a quantitative polymerase chain reaction analysis to measure microRNAs in 401 colon specimens from patients with UC, Crohn's disease, irritable bowel syndrome, sporadic colorectal cancer, or CAC, as well as subjects without these disorders (controls); levels were correlated with clinical features and disease activity of patients. Colitis was induced in mice by administration of dextran sodium sulfate (DSS), and carcinogenesis was induced by addition of azoxymethane; some mice also were given an inhibitor of microRNA214 (miR214). A high-throughput functional screen of the human microRNAome found that miR214 regulated the activity of nuclear factor-κB. Higher levels of miR214 were detected in colon tissues from patients with active UC or CAC than from patients with other disorders or controls and correlated with disease progression. Bioinformatic and genome-wide profile analyses showed that miR214 activates an inflammatory response and is amplified through a feedback loop circuit mediated by phosphatase and tensin homolog (PTEN) and PDZ and LIM domain 2 (PDLIM2). Interleukin-6 induced signal transducer and activator of transcription 3 (STAT3)-mediated transcription of miR214. A miR214 chemical inhibitor blocked this circuit and reduced the severity of DSS-induced colitis in mice, as well as the number and size of tumors that formed in mice given azoxymethane and DSS. In fresh colonic biopsy specimens from patients with active UC, the miR214 inhibitor reduced inflammation by increasing levels of PDLIM2 and PTEN. Interleukin-6 up-regulates STAT3-mediated transcription of miR214 in colon tissues, which reduces levels of PDLIM2 and PTEN

Sex Differences in the Effect of Resveratrol on DSS-Induced Colitis in Mice

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Alexandra Wagnerova

2017-01-01

Full Text Available Resveratrol is a natural polyphenol studied for its possible protective properties in inflammatory bowel diseases. Moreover, it has been shown to interact with estrogen receptors. In the present study, we aimed to investigate possible diverse effects of resveratrol on female and male mice in DSS-induced colitis. Thirty-seven C57BL/6 mice (21 female and 16 male were divided into three groups for each sex. The first group received pure water (CTRL. The other two groups received 1.5% dextran sulfate sodium (DSS to induce colitis from which one group was treated with resveratrol (DSS + RSV. Intake of 1.5% DSS caused weight loss in all DSS groups compared to control mice. Weight loss, stool consistency, and discomfort did not show any protective effect of resveratrol in males and showed even adverse effects in females. In females, the activity of myeloperoxidase was lower compared to that in males. However, colon length and spleen weight showed no sex differences, which can indicate the induction of only mild colitis in mice. Resveratrol did not have any effect on TNF-alpha levels. Taken together, these results for the first time propose possible diverse effects of resveratrol in DSS-induced colitis model depending on the sex of the animal. However, this conclusion must be confirmed by further analyses.

An endogenous aryl hydrocarbon receptor (AhR) ligand, ITE induces regulatory T cells (Tregs) and ameliorates experimental colitis.

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Abron, Jessicca D; Singh, Narendra P; Mishra, Manoj K; Price, Robert L; Nagarkatti, Mitzi; Nagarkatti, Prakash S; Singh, Udai P

2018-04-19

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that affects millions of people with high morbidity and health-care cost. The precise etiology of IBD is unknown, but clear evidence suggests that intestinal inflammation is caused by an excessive immune response to mucosal antigens. Recent studies have shown that activation of the aryl hydrocarbon receptor (AhR) induces regulatory T cells (Tregs) and suppresses autoimmune diseases. In the current study, we investigated if nontoxic ligand of AhR, 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), can attenuate dextran sodium sulphate (DSS)-induced colitis. Our studies demonstrated that in mice that received ITE treatment, in-vivo colitis pathogenesis, including a decrease in body weight, was significantly reversed along with the systemic and intestinal inflammatory cytokines. ITE increased the expression of Tregs in spleen, mesenteric lymph nodes (MLNs) and colon lamina propria lymphocytes (cLPL) of mice with colitis when compared to controls. This induction of Tregs was reversed by AhR antagonist treatment in-vitro. ITE treatment also increased dendritic cells (DCs; CD11c+) and decreased F4/80+ (macrophage) from the spleen, MLNs and cLPL in mice with colitis. ITE also reversed the systemic and intestinal frequency of CD4+T cells during colitis and suppressed inflammatory cytokines including IFN-γ, TNF-α, IL-17, IL-6 and IL-1 as well as induced IL-10 levels. These findings suggest that ITE attenuates colitis through induction of Tregs and reduction in inflammatory CD4+ T cells and cytokines. Thus, our work demonstrates that the nontoxic endogenous AhR ligand ITE, may serve as a therapeutic modality to treat IBD.

Anti-inflammatory effects of phytosteryl ferulates in colitis induced by dextran sulphate sodium in mice

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Islam, M S; Murata, T; Fujisawa, M; Nagasaka, R; Ushio, H; Bari, A M; Hori, M; Ozaki, H

2008-01-01

Background and purpose: We have recently reported that phytosteryl ferulates isolated from rice bran inhibit nuclear factor-κB (NF-κB) activity in macrophages. In the present study, we investigated the effect of γ-oryzanol (γ-ORZ), a mixture of phytosteryl ferulates, cycloartenyl ferulate (CAF), one of the components of γ-ORZ, and ferulic acid (FA), a possible metabolite of γ-ORZ in vivo, on a model of colitis in mice. Experimental approach: We induced colitis with dextran sulphate sodium (DSS) in mice and monitored disease activity index (DAI), histopathology score, tissue myeloperoxidase (MPO) activity, mRNA expressions of cytokines and COX-2, colon length, antioxidant potency and NF-κB activity in colitis tissue. Key results: Both DAI and histopathology score revealed that DSS induced a severe mucosal colitis, with a marked increase in the thickness of the muscle layer, distortion and loss of crypts, depletion of goblet cells and infiltration of macrophages, granulocytes and lymphocytes. MPO activity, pro-inflammatory cytokines and COX-2 levels, NF-κB p65 nuclear translocation and inhibitory protein of nuclear factor-κB-α degradation levels were significantly increased in DSS-induced colitis tissues. γ-ORZ (50 mg kg−1 day−1 p.o.) markedly inhibited these inflammatory reactions and CAF had a similar potency. In vitro assay demonstrated that γ-ORZ and CAF had strong antioxidant effects comparable to those of α-tocopherol. Conclusions and implications: Phytosteryl ferulates could be new potential therapeutic and/or preventive agents for gastrointestinal inflammatory diseases. Their anti-inflammatory effect could be mediated by inhibition of NF-κB activity, which was at least partly due to the antioxidant effect of the FA moiety in the structure of phytosteryl ferulates. PMID:18536734

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

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Cheng, Jian; Zhang, Lin; Dai, Weiqi; Mao, Yuqing; Li, Sainan; Wang, Jingjie; Li, Huanqing; Guo, Chuanyong; Fan, Xiaoming

2015-01-01

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 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

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

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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.

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

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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.

Impact of basal diet on dextran sodium sulphate (DSS)-induced colitis in rats.

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Boussenna, Ahlem; Goncalves-Mendes, Nicolas; Joubert-Zakeyh, Juliette; Pereira, Bruno; Fraisse, Didier; Vasson, Marie-Paule; Texier, Odile; Felgines, Catherine

2015-12-01

Dextran sodium sulphate (DSS)-induced colitis is a widely used model for inflammatory bowel disease. However, various factors including nutrition may affect the development of this colitis. This study aimed to compare and characterize the impact of purified and non-purified basal diets on the development of DSS-induced colitis in the rat. Wistar rats were fed a non-purified or a semi-synthetic purified diet for 21 days. Colitis was then induced in half of the rats by administration of DSS in drinking water (4% w/v) during the last 7 days of experimentation. At the end of the experimental period, colon sections were taken for histopathological examination, determination of various markers of inflammation (myeloperoxidase: MPO, cytokines) and oxidative stress (superoxide dismutase: SOD, catalase: CAT, glutathione peroxidase: GPx and glutathione reductase: GRed activities), and evaluation of the expression of various genes implicated in this disorder. DSS ingestion induced a more marked colitis in animals receiving the purified diet, as reflected by higher histological score and increased MPO activity. A significant decrease in SOD and CAT activities was also observed in rats fed the purified diet. Also, in these animals, administration of DSS induced a significant increase in interleukin (IL)-1α, IL-1β and IL-6. In addition, various genes implicated in inflammation were over-expressed after ingestion of DSS by rats fed the purified diet. These results show that a purified diet promotes the onset of a more severe induced colitis than a non-purified one, highlighting the influence of basal diet in colitis development.

Vanillin improves and prevents trinitrobenzene sulfonic acid-induced colitis in mice.

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Wu, Shih-Lu; Chen, Jaw-Chyun; Li, Chia-Cheng; Lo, Hsin-Yi; Ho, Tin-Yun; Hsiang, Chien-Yun

2009-08-01

Inflammatory bowel disease (IBD) is chronic inflammatory and relapsing disease of the gut. It has been known that activation of nuclear factor-kappaB (NF-kappaB) and production of proinflammatory cytokines play important roles in the pathogenesis of IBD. In this study, the effect of vanillin (4-hydroxy-3-methoxybenzaldehyde), a potent nuclear factor-kappaB (NF-kappaB) inhibitor, was evaluated in mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis. Oral administration of vanillin improved macroscopic and histological features of TNBS-induced colitis in a dose-dependent manner. Vanillin not only prevented TNBS-induced colitis but also ameliorated the established colitis. By in vivo NF-kappaB bioluminescence imaging, electrophoretic mobility shift assay, and Western blot, we found that vanillin suppressed in vivo NF-kappaB activities through the inhibition of p65 translocation, inhibitor of nuclear factor-kappaB(IkappaB)-alpha phosphorylation, and IkappaB kinase activation. Furthermore, vanillin reduced the expressions of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, interferon-gamma, and tumor necrosis factor-alpha] and stimulated the expression of anti-inflammatory cytokine (IL-4) in colonic tissues. In conclusion, this work identified vanillin as an anti-inflammatory compound with the capacity to prevent and ameliorate TNBS-induced colitis. Due to its safety, vanillin could be a potent candidate for the treatment of IBD.

Colitis susceptibility in p47(phox-/-) mice is mediated by the microbiome.

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Falcone, E Liana; Abusleme, Loreto; Swamydas, Muthulekha; Lionakis, Michail S; Ding, Li; Hsu, Amy P; Zelazny, Adrian M; Moutsopoulos, Niki M; Kuhns, Douglas B; Deming, Clay; Quiñones, Mariam; Segre, Julia A; Bryant, Clare E; Holland, Steven M

2016-04-05

Chronic granulomatous disease (CGD) is caused by defects in nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to reduced phagocyte-derived reactive oxygen species production. Almost half of patients with CGD develop inflammatory bowel disease, and the involvement of the intestinal microbiome in relation to this predisposing immunodeficiency has not been explored. Although CGD mice do not spontaneously develop colitis, we demonstrate that p47(phox-/-) mice have increased susceptibility to dextran sodium sulfate colitis in association with a distinct colonic transcript and microbiome signature. Neither restoring NOX2 reactive oxygen species production nor normalizing the microbiome using cohoused adult p47(phox-/-) with B6Tac (wild type) mice reversed this phenotype. However, breeding p47(phox+/-) mice and standardizing the microflora between littermate p47(phox-/-) and B6Tac mice from birth significantly reduced dextran sodium sulfate colitis susceptibility in p47(phox-/-) mice. We found similarly decreased colitis susceptibility in littermate p47(phox-/-) and B6Tac mice treated with Citrobacter rodentium. Our findings suggest that the microbiome signature established at birth may play a bigger role than phagocyte-derived reactive oxygen species in mediating colitis susceptibility in CGD mice. These data further support bacteria-related disease in CGD colitis.

H. pylori attenuates TNBS-induced colitis via increasing mucosal Th2 cells in mice.

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Wu, Yi-Zhong; Tan, Gao; Wu, Fang; Zhi, Fa-Chao

2017-09-26

There is an epidemiological inverse relationship between Helicobacter pylori ( H. pylori ) infection and Crohn's disease (CD). However, whether H. pylori plays a protective role against CD remains unclear. Since 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis is thought to resemble CD, we investigated whether H. pylori can attenuate TNBS-induced colitis in mice. Here we show that H. pylori can attenuate the severity of TNBS-induced colitis. In addition, H. pylori not only down-regulates Th17 and Th1 cytokine expression, but can up-regulate Th2 cytokine expression and increase the Th2:Th17 ratio of CD4 + T in the colonic mucosa of TNBS-induced colitis. Our results indicate that H. pylori attenuates TNBS-induced colitis mainly through increasing Th2 cells in murine colonic mucosa. Our finding offers a novel view on the role of H. pylori in regulating gastrointestinal immunity, and may open a new avenue for development of therapeutic strategies in CD by making use of asymptomatic H. pylori colonization.

Essential Role of Growth Hormone and IGF-1 in Therapeutic Effect of Ghrelin in the Course of Acetic Acid-Induced Colitis.

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Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Kuśnierz-Cabala, Beata; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Gil, Krzysztof; Olszanecki, Rafał; Pihut, Małgorzata; Dembiński, Artur

2017-05-24

Previous studies have shown that ghrelin exhibits a protective and therapeutic effect in the gut. The aim of the present study was to examine whether administration of ghrelin affects the course of acetic acid-induced colitis and to determine what is the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in this effect. In sham-operated or hypophysectomized male Wistar rats, colitis was induced by enema with 1 mL of 3% solution of acetic acid. Saline or ghrelin (given at the dose of 8 nmol/kg/dose) was administered intraperitoneally twice a day. Seven days after colitis induction, rats were anesthetized and the severity of the colitis was assessed. Treatment with ghrelin reduced the area of colonic mucosa damage in pituitary-intact rat. This effect was associated with increase in serum levels of GH and IGF-1. Moreover, administration of ghrelin improved blood flow in colonic mucosa and mucosal cell proliferation, as well as reduced mucosal concentration of proinflammatory interleukin-1β (IL-1β) and activity of myeloperoxidase. Hypophysectomy reduced serum levels of GH and IGF-1 and increased the area of colonic damage in rats with colitis. These effects were associated with additional reduction in mucosal blood follow and DNA synthesis when compared to pituitary-intact rats. Mucosal concentration of IL-1β and mucosal activity of myeloperoxidase were maximally increased. Moreover, in hypophysectomized rats, administration of ghrelin failed to affect serum levels of GH or IGF-1, as well as the healing rate of colitis, mucosal cell proliferation, and mucosal concentration of IL-1β, or activity of myeloperoxidase. We conclude that administration of ghrelin accelerates the healing of the acetic acid-induced colitis. Therapeutic effect of ghrelin in experimental colitis is mainly mediated by the release of endogenous growth hormone and IGF-1.

Bilirubin prevents acute DSS-induced colitis by inhibiting leukocyte infiltration and suppressing upregulation of inducible nitric oxide synthase.

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Zucker, Stephen D; Vogel, Megan E; Kindel, Tammy L; Smith, Darcey L H; Idelman, Gila; Avissar, Uri; Kakarlapudi, Ganesh; Masnovi, Michelle E

2015-11-15

Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression. Copyright © 2015 the American Physiological Society.

Lack of adrenomedullin results in microbiota changes and aggravates azoxymethane and dextran sulfate sodium-induced colitis in mice

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Sonia Martinez-Herrero

2016-11-01

Full Text Available The link between intestinal inflammation, microbiota, and colorectal cancer (CRC is intriguing and the potential underlying mechanisms remain unknown. Here we evaluate the influence of adrenomedullin (AM in microbiota composition and its impact on colitis with an inducible knockout (KO mouse model for AM. Microbiota composition was analyzed in KO and wild type (WT mice by pyrosequencing. Colitis was induced in mice by administration of azoxymethane (AOM followed by dextran sulfate sodium (DSS in the drinking water. Colitis was evaluated using a clinical symptoms index, histopathological analyses, and qRT-PCR. Abrogation of the adm gene in the whole body was confirmed by PCR and qRT-PCR. KO mice exhibit significant changes in colonic microbiota: higher proportion of δ-Proteobacteria class; of Coriobacteriales order; and of other families and genera was observed in KO feces. Meanwhile these mice had a lower proportion of beneficial bacteria, such as Lactobacillus gasseri and Bifidobacterium choerinum. TLR4 gene expression was higher (p<0.05 in KO animals. AM deficient mice treated with DSS exhibited a significantly worse colitis with profound weight loss, severe diarrhea, rectal bleeding, colonic inflammation, edema, infiltration, crypt destruction, and higher levels of pro-inflammatory cytokines. No changes were observed in the expression levels of adhesion molecules. In conclusion, we have shown that lack of AM leads to changes in gut microbiota population and in a worsening of colitis conditions, suggesting that endogenous AM is a protective mediator in this pathology.

Nitric oxide and chronic colitis

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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.

Melatonin modulates adiponectin expression on murine colitis with sleep deprivation.

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Kim, Tae Kyun; Park, Young Sook; Baik, Haing-Woon; Jun, Jin Hyun; Kim, Eun Kyung; Sull, Jae Woong; Sung, Ho Joong; Choi, Jin Woo; Chung, Sook Hee; Gye, Myung Chan; Lim, Ju Yeon; Kim, Jun Bong; Kim, Seong Hwan

2016-09-07

To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA. Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P sleep deprivation.

Phrenic motor outputs in response to bronchopulmonary C-fibre activation following chronic cervical spinal cord injury.

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Lee, Kun-Ze

2016-10-15

Activation of bronchopulmonary C-fibres, the main chemosensitive afferents in the lung, can induce pulmonary chemoreflexes to modulate respiratory activity. Following chronic cervical spinal cord injury, bronchopulmonary C-fibre activation-induced inhibition of phrenic activity was exaggerated. Supersensitivity of phrenic motor outputs to the inhibitory effect of bronchopulmonary C-fibre activation is due to a shift of phrenic motoneuron types and slow recovery of phrenic motoneuron discharge in cervical spinal cord-injured animals. These data suggest that activation of bronchopulmonary C-fibres may retard phrenic output recovery following cervical spinal cord injury. The alteration of phenotype and discharge pattern of phrenic motoneuron enables us to understand the impact of spinal cord injury on spinal respiratory activity. Cervical spinal injury interrupts bulbospinal pathways and results in cessation of phrenic bursting ipsilateral to the lesion. The ipsilateral phrenic activity can partially recover over weeks to months following injury due to the activation of latent crossed spinal pathways and exhibits a greater capacity to increase activity during respiratory challenges than the contralateral phrenic nerve. However, whether the bilateral phrenic nerves demonstrate differential responses to respiratory inhibitory inputs is unclear. Accordingly, the present study examined bilateral phrenic bursting in response to capsaicin-induced pulmonary chemoreflexes, a robust respiratory inhibitory stimulus. Bilateral phrenic nerve activity was recorded in anaesthetized and mechanically ventilated adult rats at 8-9 weeks after C2 hemisection (C2Hx) or C2 laminectomy. Intra-jugular capsaicin (1.5 μg kg -1 ) injection was performed to activate the bronchopulmonary C-fibres to evoke pulmonary chemoreflexes. The present results indicate that capsaicin-induced prolongation of expiratory duration was significantly attenuated in C2Hx animals. However, ipsilateral phrenic

Membrane-bound Dickkopf-1 in Foxp3+ regulatory T cells suppresses T-cell-mediated autoimmune colitis.

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Chae, Wook-Jin; Park, Jong-Hyun; Henegariu, Octavian; Yilmaz, Saliha; Hao, Liming; Bothwell, Alfred L M

2017-10-01

Induction of tolerance is a key mechanism to maintain or to restore immunological homeostasis. Here we show that Foxp3 + regulatory T (Treg) cells use Dickkopf-1 (DKK-1) to regulate T-cell-mediated tolerance in the T-cell-mediated autoimmune colitis model. Treg cells from DKK-1 hypomorphic doubleridge mice failed to control CD4 + T-cell proliferation, resulting in CD4 T-cell-mediated autoimmune colitis. Thymus-derived Treg cells showed a robust expression of DKK-1 but not in naive or effector CD4 T cells. DKK-1 expression in Foxp3 + Treg cells was further increased upon T-cell receptor stimulation in vitro and in vivo. Interestingly, Foxp3 + Treg cells expressed DKK-1 in the cell membrane and the functional inhibition of DKK-1 using DKK-1 monoclonal antibody abrogated the suppressor function of Foxp3 + Treg cells. DKK-1 expression was dependent on de novo protein synthesis and regulated by the mitogen-activated protein kinase pathway but not by the canonical Wnt pathway. Taken together, our results highlight membrane-bound DKK-1 as a novel Treg-derived mediator to maintain immunological tolerance in T-cell-mediated autoimmune colitis. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.

Glycyrrhetic Acid Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Vivo

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Yong-Deok Jeon

2016-04-01

Full Text Available Glycyrrhizae Radix (GR is a Korean traditional herb medicine that is widely used in clinical health care. Glycyrrhetic acid (GA is an aglycone saponin extracted from GR that has anti-inflammatory, anti-cancer, and anti-viral effects. However, the anti-inflammatory effects of GA in colitis have not been reported. This study investigated the role of GA on ulcerative colitis in a dextran sulfate sodium (DSS-induced mouse colitis model. DSS-treated mice displayed weight loss and shortened colon length compared with control mice. Mice administered GA showed less weight loss and longer colon length than the DSS-treated group. Interleukin (IL-6, IL-1β, and tumor necrosis factor-alpha were decreased by GA treatment. GA treatment also reduced DSS-induced microscopic damage to colon tissue. GA regulates the phosphorylation of transcription factors including nuclear factor-kappa B (NF-κB and IκB alpha, and regulates the expression of cycloxygenase-2 and prostaglandin E2. GA thus showed beneficial effects in a mouse model of colitis, implicating GA might be a useful herb-derived medicine in the treatment of ulcerative colitis.

Intermittent fasting prompted recovery from dextran sulfate sodium-induced colitis in mice.

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Okada, Toshihiko; Otsubo, Takeshi; Hagiwara, Teruki; Inazuka, Fumika; Kobayashi, Eiko; Fukuda, Shinji; Inoue, Takuya; Higuchi, Kazuhide; Kawamura, Yuki I; Dohi, Taeko

2017-09-01

Fasting-refeeding in mice induces transient hyperproliferation of colonic epithelial cells, which is dependent on the lactate produced as a metabolite of commensal bacteria. We attempted to manipulate colonic epithelial cell turnover with intermittent fasting to prompt recovery from acute colitis. Acute colitis was induced in C57BL/6 mice by administration of dextran sulfate sodium in the drinking water for 5 days. From day 6, mice were fasted for 36 h and refed normal bait, glucose powder, or lactylated high-amylose starch. On day 9, colon tissues were subjected to analysis of histology and cytokine expression. The effect of lactate on the proliferation of colonocytes was assessed by enema in vivo and primary culture in vitro . Intermittent fasting resulted in restored colonic crypts and less expression of interleukin-1β and interleukin-17 in the colon than in mice fed ad libitum . Administration of lactate in the colon at refeeding time by enema or by feeding lactylated high-amylose starch increased the number of regenerating crypts. Addition of lactate but not butyrate or acetate supported colony formation of colonocytes in vitro . In conclusion, intermittent fasting in the resolution phase of acute colitis resulted in better recovery of epithelial cells and reduced inflammation.

The Influence of Ghrelin on the Development of Dextran Sodium Sulfate-Induced Colitis in Rats

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Aleksandra Matuszyk

2015-01-01

Full Text Available Ghrelin has protective and therapeutic effects in the gut. The aim of present studies was to investigate the effect of treatment with ghrelin on the development of colitis evoked by dextran sodium sulfate (DSS. Methods. Studies have been performed on rats. Colitis was induced by adding 5% DSS to the drinking water for 5 days. During this period animals were treated intraperitoneally twice a day with saline or ghrelin given at the dose of 8 nmol/kg/dose. On the sixth day, animals were anesthetized and the severity of colitis was assessed. Results. Treatment with ghrelin during administration of DSS reduced the development of colitis. Morphological features of colonic mucosa exhibited a reduction in the area and deep of mucosal damage. Ghrelin reversed the colitis-induced decrease in blood flow, DNA synthesis, and superoxide dismutase activity in colonic mucosa. These effects were accompanied by a decrease in the colitis-evoked increase in mucosal concentration of interleukin-1β and malondialdehyde. Treatment with ghrelin reversed the DSS-induced reduction in body weight gain. Conclusions. Administration of ghrelin exhibits the preventive effect against the development of DSS-induced colitis. This effect seems to be related to ghrelin’s anti-inflammatory and antioxidative properties.

Nox4 Is Dispensable for Exercise Induced Muscle Fibre Switch.

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Juri Vogel

Full Text Available By producing H2O2, the NADPH oxidase Nox4 is involved in differentiation of mesenchymal cells. Exercise alters the composition of slow and fast twitch fibres in skeletal. Here we hypothesized that Nox4 contributes to exercise-induced adaptation such as changes in muscle metabolism or muscle fibre specification and studied this in wildtype and Nox4-/- mice.Exercise, as induced by voluntary running in a running wheel or forced running on a treadmill induced a switch from fast twitch to intermediate fibres. However the induced muscle fibre switch was similar between Nox4-/- and wildtype mice. The same held true for exercise-induced expression of PGC1α or AMPK activation. Both are increased in response to exercise, but with no difference was observed between wildtype and Nox4-/- mice.Thus, exercise-induced muscle fibre switch is Nox4-independent.

Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid-Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis

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Brown, Kirsty; Rajendiran, Ethendhar; Estaki, Mehrbod; Dai, Chuanbin; Yip, Ashley; Gibson, Deanna L.

2013-01-01

Clinically, excessive ω-6 polyunsaturated fatty acid (PUFA) and inadequate ω-3 PUFA have been associated with enhanced risks for developing ulcerative colitis. In rodent models, ω-3 PUFAs have been shown to either attenuate or exacerbate colitis in different studies. We hypothesized that a high ω-6: ω-3 PUFA ratio would increase colitis susceptibility through the microbe-immunity nexus. To address this, we fed post-weaned mice diets rich in ω-6 PUFA (corn oil) and diets supplemented with ω-3 PUFA (corn oil+fish oil) for 5 weeks. We evaluated the intestinal microbiota, induced colitis with Citrobacter rodentium and followed disease progression. We found that ω-6 PUFA enriched the microbiota with Enterobacteriaceae, Segmented Filamentous Bacteria and Clostridia spp., all known to induce inflammation. During infection-induced colitis, ω-6 PUFA fed mice had exacerbated intestinal damage, immune cell infiltration, prostaglandin E2 expression and C. rodentium translocation across the intestinal mucosae. Addition of ω-3 PUFA on a high ω-6 PUFA diet, reversed inflammatory-inducing microbial blooms and enriched beneficial microbes like Lactobacillus and Bifidobacteria, reduced immune cell infiltration and impaired cytokine/chemokine induction during infection. While, ω-3 PUFA supplementation protected against severe colitis, these mice suffered greater mortality associated with sepsis-related serum factors such as LPS binding protein, IL-15 and TNF-α. These mice also demonstrated decreased expression of intestinal alkaline phosphatase and an inability to dephosphorylate LPS. Thus, the colonic microbiota is altered differentially through varying PUFA composition, conferring altered susceptibility to colitis. Overall, ω-6 PUFA enriches pro-inflammatory microbes and augments colitis; but prevents infection-induced systemic inflammation. In contrast, ω-3 PUFA supplementation reverses the effects of the ω-6 PUFA diet but impairs infection-induced responses

Interactive effects of ethanol on ulcerative colitis and its associated testicular dysfunction in pubertal BALB/c mice.

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Adedara, Isaac A; Ajayi, Babajide O; Awogbindin, Ifeoluwa O; Farombi, Ebenezer O

2017-11-01

Available epidemiological reports have indicated an increase in the incidence of ulcerative colitis, as well as alcohol consumption, globally. The present study investigated the possible interactive effects of ethanol consumption on ulcerative colitis and its associated testicular dysfunction using six groups of 12 pubertal mice each. Group I (Control) mice received drinking water alone. Group II mice received ethanol alone at 5 g/kg body weight. Group III mice received 2.5% dextran sulphate sodium (DSS) in drinking water followed by normal drinking water. Groups IV, V, and VI mice received DSS followed by ethanol at 1.25, 2.5, and 5 g/kg, respectively. Administration of ethanol to mice with ulcerative colitis intensified the disease-activity index with marked reduction in colon length, colon mass index, body weight gain, and organo-somatic indices of testes and epididymis when compared with the DSS-alone group. Moreover, ethanol exacerbated colitis-mediated decrease in enzymatic and non-enzymatic antioxidants but increased the oxidative stress and inflammatory biomarkers in the testes and epididymis. The diminution in luteinizing hormone, follicle stimulating hormone, and testosterone levels was intensified following administration of ethanol to mice with ulcerative colitis that were administered 5 g/kg ethanol alone. The decrease in sperm functional parameters and testicular spermatogenic indices as well as histopathological damage in colon, testes, and epididymis was aggravated following administration of ethanol to mice with ulcerative colitis. In conclusion, the exacerbating effects of ethanol on ulcerative colitis-induced testicular dysfunction are related to increased oxidative stress and inflammation in the treated mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Co-administration of α-lipoic acid and cyclosporine aggravates colon ulceration of acetic acid-induced ulcerative colitis via facilitation of NO/COX-2/miR-210 cascade

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El-Gowelli, Hanan M., E-mail: dr_Hanan_el_gowali@hotmail.com; Saad, Evan I.; Abdel-Galil, Abdel-Galil A.; Ibrahim, Einas R.

2015-11-01

In this work, α-lipoic acid and cyclosporine demonstrated significant protection against acetic acid-induced ulcerative colitis in rats. We proposed that α-lipoic acid and cyclosporine co-administration might modulate their individual effects. Induction of ulcerative colitis in rats was performed by intra-rectal acetic acid (5% v/v) administration for 3 consecutive days. Effects of individual or combined used of α-lipoic acid (35 mg/kg ip) or cyclosporine (5 mg/kg sc) for 6 days starting 2 days prior to acetic acid were assessed. Acetic acid caused colon ulceration, bloody diarrhea and weight loss. Histologically, there was mucosal atrophy and inflammatory cells infiltration in submucosa, associated with depletion of colon reduced glutathione, superoxide dismutase and catalase activities and elevated colon malondialdehyde, serum C-reactive protein (C-RP) and tumor necrosis factor-α (TNF-α). Colon gene expression of cyclooxygenase-2 and miR-210 was also elevated. These devastating effects of acetic acid were abolished upon concurrent administration of α-lipoic acid. Alternatively, cyclosporine caused partial protection against acetic acid-induced ulcerative colitis. Cyclosporine did not restore colon reduced glutathione, catalase activity, serum C-RP or TNF-α. Unexpectedly, co-administration of α-lipoic acid and cyclosporine aggravated colon ulceration. Concomitant use of α-lipoic acid and cyclosporine significantly increased nitric oxide production, cyclooxygenase-2 and miR-210 gene expression compared to all other studied groups. The current findings suggest that facilitation of nitric oxide/cyclooxygenase-2/miR-210 cascade constitutes, at least partially, the cellular mechanism by which concurrent use of α-lipoic acid and cyclosporine aggravates colon damage. Collectively, the present work highlights the probable risk of using α-lipoic acid/cyclosporine combination in ulcerative colitis patients. - Highlights: • Lipoic acid is more effective than

Adoptive transfer of dendritic cells expressing CD11c reduces the immunological response associated with experimental colitis in BALB/c mice.

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Paiatto, Lisiery N; Silva, Fernanda G D; Yamada, Áureo T; Tamashiro, Wirla M S C; Simioni, Patricia U

2018-01-01

In addition to conventional therapies, several new strategies have been proposed for modulating autoimmune diseases, including the adoptive transfer of immunological cells. In this context, dendritic cells (DCs) appear to be one of the most promising treatments for autoimmune disorders. The present study aimed to evaluate the effects of adoptive transfer of DCs obtained from both naïve and ovalbumin (OVA)-tolerant mice on the severity of TNBS induced colitis and analyze the eventual protective mechanisms. To induce oral tolerance, BALB/c mice were fed 4mg/mL OVA solution for seven consecutive days. Spleen DCs were isolated from tolerant (tDC) and naïve (nDC) mice, and then adoptively transferred to syngeneic mice. Three days later, colitis was induced in DC treated mice by intrarectal instillation of 100μg2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Control subjects received only intrarectal instillation of either TNBS solution or a vehicle. Five days later, mice from all groups were euthanized and examined for physiological and immunological parameters. Regarding the phenotype, we observed that the frequencies of CD11+ MHC II+ and CD11+ MHCII+ CD86+ cells were significantly lower in DCs isolated from tolerant mice than in those from naive mice. However, pretreatment with both types of DCs was able to significantly reduce clinical signs of colitis such as diarrhea, rectal prolapse, bleeding, and cachexia, although only treatment with tDCs was able to prevent weight loss from instillation of TNBS. In vitro proliferation of spleen cells from mice treated with either type of DCs was significantly lower than that observed in splenic cell cultures of naïve mice. Although no significant difference was observed in the frequencies of Treg cells in the experimental groups, the frequency of Th17+CD4+cellsand the secretion of IL-17 were more reduced in the cultures of spleen cells from mice treated with either type of DCs. The levels of IL-9 and IFN

Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases

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Huang, T.-Y.; Chu, H.-C.; Lin, Y.-L.; Lin, C.-K.; Hsieh, T.-Y.; Chang, W.-K.; Chao, Y.-C.; Liao, C.-L.

2009-01-01

In addition to its antimicrobial activity, minocycline exerts anti-inflammatory effects in several disease models. However, whether minocycline affects the pathogenesis of inflammatory bowel disease has not been determined. We investigated the effects of minocycline on experimental colitis and its underlying mechanisms. Acute and chronic colitis were induced in mice by treatment with dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS), and the effect of minocycline on colonic injury was assessed clinically and histologically. Prophylactic and therapeutic treatment of mice with minocycline significantly diminished mortality rate and attenuated the severity of DSS-induced acute colitis. Mechanistically, minocycline administration suppressed inducible nitric oxide synthase (iNOS) expression and nitrotyrosine production, inhibited proinflammatory cytokine expression, repressed the elevated mRNA expression of matrix metalloproteinases (MMPs) 2, 3, 9, and 13, diminished the apoptotic index in colonic tissues, and inhibited nitric oxide production in the serum of mice with DSS-induced acute colitis. In DSS-induced chronic colitis, minocycline treatment also reduced body weight loss, improved colonic histology, and blocked expression of iNOS, proinflammatory cytokines, and MMPs from colonic tissues. Similarly, minocycline could ameliorate the severity of TNBS-induced acute colitis in mice by decreasing mortality rate and inhibiting proinflammatory cytokine expression in colonic tissues. These results demonstrate that minocycline protects mice against DSS- and TNBS-induced colitis, probably via inhibition of iNOS and MMP expression in intestinal tissues. Therefore, minocycline is a potential remedy for human inflammatory bowel diseases.

The Probiotic Lactobacillus Prevents Citrobacter rodentium-Induced Murine Colitis in a TLR2-Dependent Manner.

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Ryu, Seung-Hyun; Park, Jong-Hyung; Choi, Soo-Young; Jeon, Hee-Yeon; Park, Jin-Il; Kim, Jun-Young; Ham, Seung-Hoon; Choi, Yang-Kyu

2016-07-28

The main objective of this study was to investigate whether Lactobacillus rhamnosus GG (LGG) ameliorated the effects of Citrobactor rodentium infection in Toll-like receptor 2 (TLR2) knockout (KO) and TLR4 KO mice, as well as in wild-type C57BL/6 (B6) mice. TLR2 KO, TLR4 KO, and B6 mice were divided into three groups per each strain. Each group had an uninfected control group (n = 5), C. rodentium-infected group (n = 8), and LGG-pretreated C. rodentium-infected group (n = 8). The survival rate of B6 mice infected with C. rodentium was higher when pretreated with LGG. Pretreatment with LGG ameliorated C. rodentium-induced mucosal hyperplasia in B6 and TLR4 KO mice. However, in C-rodentium-infected TLR2 KO mice, mucosal hyperplasia persisted, regardless of pretreatment with LGG. In addition, LGG-pretreated B6 and TLR4 KO mice showed a decrease in spleen weight and downregulation of tumor necrosis factor alpha, interferon gamma, and monocyte chemotactic protein 1 mRNA expression compared with the non-pretreated group. In contrast, such changes were not observed in TLR2 KO mice, regardless of pretreatment with LGG. From the above results, we conclude that pretreatment with LGG ameliorates C. rodentium-induced colitis in B6 and TLR4 KO mice, but not in TLR2 KO mice. Therefore, LGG protects mice from C. rodentium-induced colitis in a TLR2-dependent manner.

NKT cells mediate the recruitment of neutrophils by stimulating epithelial chemokine secretion during colitis.

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Huang, Enyu; Liu, Ronghua; Lu, Zhou; Liu, Jiajing; Liu, Xiaoming; Zhang, Dan; Chu, Yiwei

2016-05-27

Ulcerative colitis (UC) is a kind of inflammatory bowel diseases characterized by chronic inflammation and ulcer in colon, and UC patients have increased risk of getting colorectal cancer. NKT cells are cells that express both NK cell markers and semi-invariant CD1d-restricted TCRs, can regulate immune responses via secreting a variety of cytokines upon activation. In our research, we found that the NKT cell-deficient CD1d(-/-) mice had relieved colitis in the DSS-induced colitis model. Further investigations revealed that the colon of CD1d(-/-) mice expressed less neutrophil-attracting chemokine CXCL 1, 2 and 3, and had decreased neutrophil infiltration. Infiltrated neutrophils also produced less reactive oxygen species (ROS) and TNF-α, indicating they may cause less epithelial damage. In addition, colitis-associated colorectal cancer was also relieved in CD1d(-/-) mice. During colitis, NKT cells strongly expressed TNF-α, which could stimulate CXCL 1, 2, 3 expressions by the epithelium. In conclusion, NKT cells can regulate colitis via the NKT cell-epithelium-neutrophil axis. Targeting this mechanism may help to improve the therapy of UC and prevent colitis-associated colorectal cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Dietary Supplementation of Fermented Rice Bran Effectively Alleviates Dextran Sodium Sulfate-Induced Colitis in Mice

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Jahidul Islam

2017-07-01

Full Text Available Rice bran (RB is a major by-product of rice polishing and a rich source of bioactive compounds. Here, we investigated the anti-colitis effect of diet supplementation with fermented rice bran (FRB in a murine model of ulcerative colitis. FRB was prepared by dual fermentation of RB using fungi and lactic acid bacteria. Colitis was induced in C57Bl/6N male mice (n = 8/group by dextran sodium sulfate (DSS. Body weight change, disease activity index (DAI, histopathology score, tissue myeloperoxidase (MPO activity, cytokine and chemokine transcript levels, and the production of short-chain fatty acids (SCFAs and mucin in the colonic tissue were monitored. Based on histopathology scores, DSS induced severe mucosal inflammation, with an increased loss of crypts, and inflammatory cell infiltration in the control and RB groups, but not in the FRB group. MPO activity, thiobarbituric acid-reactive substance levels, and pro-inflammatory cytokine transcript (Tnf-α, Il-1β, Il-6, and Il-17 levels were significantly higher in the control and RB groups than in the FRB group. Thus, dietary FRB attenuated intestinal inflammation owing to elevated SCFAs and tryptamine production, which might regulate tight junction barrier integrity and intestinal homeostasis. These results suggest that FRB could comprise an effective potential preventive agent for ulcerative colitis.

Hydrogen peroxide scavenger, catalase, alleviates ion transport dysfunction in murine colitis.

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Barrett, Kim E; McCole, Declan F

2016-11-01

Reactive oxygen species (ROS) such as hydrogen peroxide (H 2 O 2 ) contribute to epithelial damage and ion transport dysfunction (key events in inflammatory diarrhoea) in inflammatory bowel disease (IBD). The aim of this study was to identify if H 2 O 2 mediates suppression of colonic ion transport function in the murine dextran sulfate sodium (DSS) colitis model by using the H 2 O 2 degrading enzyme, catalase. Colitis was induced by administering DSS (4%) in drinking water for 5 days followed by 3 days on normal H 2 O. Mice were administered either pegylated catalase or saline at day -1, 0 and +1 of DSS treatment. Ion transport responses to the Ca 2+ -dependent agonist, carbachol (CCh), or the cAMP-dependent agonist, forskolin, were measured across distal colonic mucosa mounted in Ussing chambers. Parameters of DSS-induced inflammation (loss in body weight, decreased colon length, altered stool consistency), were only partially alleviated by catalase while histology was only minimally improved. However, catalase significantly reversed the DSS-induced reduction in baseline ion transport as well as colonic I sc responses to CCh. However, ion transport responses to forskolin were not significantly restored. Catalase also reduced activation of ERK MAP kinase in the setting of colitis, and increased expression of the Na + -K + -2Cl - cotransporter, NKCC1, consistent with restoration of ion transport function. Ex vivo treatment of inflamed colonic mucosae with catalase also partially restored ion transport function. Therefore, catalase partially prevents, and rescues, the loss of ion transport properties in DSS colitis even in the setting of unresolved tissue inflammation. These findings indicate a prominent role for ROS in ion transport dysfunction in colitis and may suggest novel strategies for the treatment of inflammatory diarrhoea. © 2016 John Wiley & Sons Australia, Ltd.

Safety and efficacy of Profermin(R) to induce remission in ulcerative colitis

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Krag, Aleksander; Israelsen, Hans; von Ryberg, Bjørn

2012-01-01

AIM: To test the efficacy and safety of Profermin(R) in inducing remission in patients with active ulcerative colitis (UC). METHODS: The study included 39 patients with mild to moderate UC defined as a Simple Clinical Colitis Activity Index (SCCAI) > 4 and < 12 (median: 7.5), who were treated ope...

Dextran sulfate sodium-induced colitis in piglets

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Nielsen, Katrine Dalby; Schramm, Andreas; Purup, Stig

Inflammatory bowel disease (IBD) results from complex interactions between genetic and environmental factors. Although a genetic contribution has been proven, dietary factors have also shown to play a role in the development of IBD. This study aims to investigate the effect of adding red meatto t...... the diet of piglets in a dextran sodium sulfate (DSS)-induced colitis model....

Antiinflammatory effects of Cordia myxa fruit on experimentally induced colitis in rats.

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Al-Awadi, F M; Srikumar, T S; Anim, J T; Khan, I

2001-05-01

Products of certain species of Cordia are reported to have antiinflammatory properties. In the present study we examined the effects of Cordia myxa fruit on experimentally induced colitis in rats. Colitis was induced by intrarectal administration of 4% acetic acid. Colitic, normal, and corresponding control animals were included. Body weight was recorded daily. All the animals were sacrificed 4 days after the fruit treatment. Colitis was monitored histologically and by activity of myeloperoxidase. Glutathione peroxidase, superoxide dismutase, as well as total antioxidant status and concentrations of zinc, copper, manganese, selenium, and iron were assayed in plasma, liver, and colon using standard methods. Histology of the colon of colitic rats showed acute colitis that was confirmed by a significant increase in the myeloperoxidase activity. Colitis was associated with significant decreases in the tissue activities of glutathione peroxidase and superoxide dismutase and lower concentrations of trace elements. Histologic examination and myeloperoxidase activity showed that the fruit treatment reversed the above findings in the inflamed colon, and in liver and plasma of colitic rats. The present results suggest that the observed antiinflammatory effect of the Cordia myxa may be attributed partly to its antioxidant property and to restoration of the levels of trace elements in the inflamed colon, liver, and plasma.

Rnd3 induces stress fibres in endothelial cells through RhoB

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Undine Gottesbühren

2012-12-01

Rnd proteins are atypical Rho family proteins that do not hydrolyse GTP and are instead regulated by expression levels and post-translational modifications. Rnd1 and Rnd3/RhoE induce loss of actin stress fibres and cell rounding in multiple cell types, whereas responses to Rnd2 are more variable. Here we report the responses of endothelial cells to Rnd proteins. Rnd3 induces a very transient decrease in stress fibres but subsequently stimulates a strong increase in stress fibres, in contrast to the reduction observed in other cell types. Rnd2 also increases stress fibres whereas Rnd1 induces a loss of stress fibres and weakening of cell–cell junctions. Rnd3 does not act through any of its known signalling partners and does not need to associate with membranes to increase stress fibres. Instead, it acts by increasing RhoB expression, which is then required for Rnd3-induced stress fibre assembly. Rnd2 also increases RhoB levels. These data indicate that the cytoskeletal response to Rnd3 expression is dependent on cell type and context, and identify regulation of RhoB as a new mechanism for Rnd proteins to affect the actin cytoskeleton.

Muscadine Grape (Vitis rotundifolia) or Wine Phytochemicals Reduce Intestinal Inflammation in Mice with Dextran Sulfate Sodium-Induced Colitis.

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Li, Ruiqi; Kim, Min-Hyun; Sandhu, Amandeep K; Gao, Chi; Gu, Liwei

2017-02-01

The objective of this study was to determine the anti-inflammatory effects of phytochemical extracts from muscadine grapes or wine on dextran sulfate sodium (DSS)-induced colitis in mice and to investigate cellular mechanisms. Two groups of C57BL/6J mice were gavaged with muscadine grape phytochemicals (MGP) or muscadine wine phytochemicals (MWP), respectively, for 14 days. Acute colitis was induced by 3% DSS in drinking water for 7 days. An additional two groups of mice served as healthy and disease controls. Results indicated that MGP or MWP significantly prevented weight loss, reduced disease activity index, and preserved colonic length compared to the colitis group (p ≤ 0.05). MGP or MWP significantly decreased myeloperoxidase activity as well as the levels of IL-1β, IL-6, and TNF-α in colon (p ≤ 0.05). MGP or MWP caused down-regulation of the NF-κB pathway by inhibiting the phosphorylation and degradation of IκB in a dose-dependent manner. These findings suggest that phytochemicals from muscadine grape or wine mitigate ulcerative colitis via attenuation of pro-inflammatory cytokine production and modulation of the NF-κB pathway.

Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice.

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Agollah, Germaine D; Wu, Grace; Peng, Ho-Lan; Kwon, Sunkuk

2015-12-07

To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired

The Hydrogen Peroxide Scavenger, Catalase, Alleviates Ion Transport Dysfunction in Murine Colitis

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Barrett, Kim E.; McCole, Declan F.

2016-01-01

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) contribute to epithelial damage and ion transport dysfunction (key events in inflammatory diarrhea) in inflammatory bowel disease (IBD). The aim of this study was to identify if H2O2 mediates suppression of colonic ion transport function in the murine dextran sulfate sodium (DSS) colitis model by using the H2O2 degrading enzyme, catalase. Colitis was induced by administering DSS (4%) in drinking water for 5 days followed by 3 days on normal H2O. Mice were administered either pegylated-catalase or saline at day −1, 0 and +1 of DSS treatment. Ion transport responses to the Ca2+-dependent agonist, carbachol (CCh), or the cAMP-dependent agonist, forskolin, were measured across distal colonic mucosa mounted in Ussing chambers. Parameters of DSS-induced inflammation (loss in body weight, decreased colon length, altered stool consistency), were only partially alleviated by catalase while histology was only minimally improved. However, catalase significantly reversed the DSS-induced reduction in baseline ion transport as well as colonic Isc responses to CCh. However, ion transport responses to forskolin were not significantly restored. Catalase also reduced activation of ERK MAP kinase in the setting of colitis, and increased expression of the Na+-K+-2Cl− cotransporter, NKCC1, consistent with restoration of ion transport function. Ex vivo treatment of inflamed colonic mucosae with catalase also partially restored ion transport function. Therefore, catalase partially prevents, and rescues, the loss of ion transport properties in DSS colitis even in the setting of unresolved tissue inflammation. These findings indicate a prominent role for ROS in ion transport dysfunction in colitis and may suggest novel strategies for the treatment of inflammatory diarrhea. PMID:27543846

Environmental enrichment and gut inflammation modify stress-induced c-Fos expression in the mouse corticolimbic system.

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Florian Reichmann

Full Text Available Environmental enrichment (EE has a beneficial effect on rodent behaviour, neuronal plasticity and brain function. Although it may also improve stress coping, it is not known whether EE influences the brain response to an external (psychological stressor such as water avoidance stress (WAS or an internal (systemic stressor such as gastrointestinal inflammation. This study hence explored whether EE modifies WAS-induced activation of the mouse corticolimbic system and whether this stress response is altered by gastritis or colitis. Male C67BL/6N mice were housed under standard or enriched environment for 9 weeks, after which they were subjected to a 1-week treatment with oral iodoacetamide to induce gastritis or oral dextran sulfate sodium to induce colitis. Following exposure to WAS the expression of c-Fos, a marker of neuronal activation, was measured by immunocytochemistry. EE aggravated experimentally induced colitis, but not gastritis, as shown by an increase in the disease activity score and the colonic myeloperoxidase content. In the brain, EE enhanced the WAS-induced activation of the dentate gyrus and unmasked an inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression within this part of the hippocampus. Conversely, EE inhibited the WAS-evoked activation of the central amygdala and prevented the inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression in this region. EE, in addition, blunted the WAS-induced activation of the infralimbic cortex and attenuated the inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression in this area. These data reveal that EE has a region-specific effect on stress-induced c-Fos expression in the corticolimbic system, which is likely to improve stress resilience. The response of the prefrontal cortex - amygdala - hippocampus circuitry to psychological stress is also modified by the systemic stress of gut inflammation, and this interaction between external

Radiologic findings in taxane induced colitis

International Nuclear Information System (INIS)

Kaur, Harmeet; Loyer, Evelyne M.; David, Cynthia L.; Sawaf, Hassan; DuBrow, Ronelle A.; Ibrahim, Nuhad K.

2008-01-01

Ischemic colitis in breast cancer patients being treated with taxane-based chemotherapy, which may lead to serious morbidities and even death, has recently been defined as a clinical entity. The purpose of this retrospective study was to evaluate the computed tomography (CT) findings in taxane-related colitis and determine their clinical relevance. CT scans of 41 patients at risk for taxane colitis were reviewed retrospectively for bowel and peritoneal abnormalities. Morphological findings were analyzed and correlated with clinical, pathological, and endoscopic findings. CT scans in 10 of the 41 patients showed a definitely abnormal colon with a thickened wall or distended with fluid, signs that are suggestive of colitis, in the context of the clinical picture. Radiographic changes in patients with taxane colitis are not specific but, in the appropriate context, can suggest the correct diagnosis and guide the patient's management

Frondanol, a Nutraceutical Extract from Cucumaria frondosa, Attenuates Colonic Inflammation in a DSS-Induced Colitis Model in Mice

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Sandeep B. Subramanya

2018-04-01

Full Text Available Frondanol is a nutraceutical lipid extract of the intestine of the edible Atlantic sea cucumber, Cucumaria frondosa, with potent anti-inflammatory effects. In the current study, we investigated Frondanol as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J were given 3% dextran sodium sulfate (DSS in drinking water for 7 days to induce colitis. The colitis group received oral Frondanol (100 mg/kg body weight/per day by gavage and were compared with a control group and the DSS group. Disease activity index (DAI and colon histology were scored for macroscopic and microscopic changes. Colonic tissue length, myeloperoxidase (MPO concentration, neutrophil and macrophage marker mRNA, pro-inflammatory cytokine proteins, and their respective mRNAs were measured using ELISA and real-time RT-PCR. The tissue content of leukotriene B4 (LTB4 was also measured using ELISA. Frondanol significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue MPO concentrations, neutrophil and macrophage mRNA expression (F4/80 and MIP-2, and pro-inflammatory cytokine content (IL-1β, IL-6 and TNF-α both at the protein and mRNA level were significantly reduced by Frondanol. The increase in content of the pro-inflammatory mediator leukotriene B4 (LTB4 induced by DSS was also significantly inhibited by Frondanol. It was thus found that Frondanol supplementation attenuates colon inflammation through its potent anti-inflammatory activity.

Investigations on d.c. conductivity behaviour of milled carbon fibre ...

Indian Academy of Sciences (India)

This paper reports the d.c. conductivity behaviour of milled carbon fibre reinforced polysulphide modified epoxy gradient composites. Milled carbon fibre reinforced composites having 3 vol. % of milled carbon fibre and poly sulphide modified epoxy resin have been developed. D.C. conductivity measurements are conducted ...

Goniothalamin prevents the development of chemically induced and spontaneous colitis in rodents and induces apoptosis in the HT-29 human colon tumor cell line

Energy Technology Data Exchange (ETDEWEB)

Vendramini-Costa, Débora Barbosa, E-mail: vendramini.debora@gmail.com [Department of Organic Chemistry, Institute of Chemistry, University of Campinas, Campinas, SP (Brazil); Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), University of Campinas, Campinas, SP (Brazil); Alcaide, Antonio [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain); Pelizzaro-Rocha, Karin Juliane [Department of Biochemistry, Institute of Biology, University of Campinas, Campinas, SP (Brazil); Talero, Elena; Ávila-Román, Javier [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain); Garcia-Mauriño, Sofia [Department of Plant Biology and Ecology, Faculty of Biology, University of Seville, Seville (Spain); Pilli, Ronaldo Aloise [Department of Organic Chemistry, Institute of Chemistry, University of Campinas, Campinas, SP (Brazil); Carvalho, João Ernesto de [Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), University of Campinas, Campinas, SP (Brazil); Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, SP (Brazil); Motilva, Virginia [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain)

2016-06-01

Colon cancer is the third most incident type of cancer worldwide. One of the most important risk factors for colon cancer development are inflammatory bowel diseases (IBD), thus therapies focusing on IBD treatment have great potential to be used in cancer prevention. Nature has been a source of new therapeutic and preventive agents and the racemic form of the styryl-lactone goniothalamin (GTN) has been shown to be a promising antiproliferative agent, with gastroprotective, antinociceptive and anti-inflammatory effects. As inflammation is a well-known tumor promoter, the major goal of this study was to evaluate the therapeutic and preventive potentials of GTN on chemically induced and spontaneous colitis, as well as the cytotoxic effects of GTN on a human colon tumor cell line (HT-29). GTN treatments inhibited TNBS-induced acute and chronic colitis development in Wistar rats, reducing myeloperoxidase levels and inflammatory cells infiltration in the mucosa. In spontaneous-colitis using IL-10 deficient mice (C57BL/6 background), GTN prevented colitis development through downregulation of TNF-α, upregulation of SIRT-1 and inhibition of proliferation (PCNA index), without signs of toxicity after three months of treatment. In HT-29 cells, treatment with 10 μM of GTN induced apoptosis by increasing BAX/BCL2, p-JNK1/JNK1, p-P38/P38 ratios as well as through ROS generation. Caspase 8, 9 and 3 activation also occurred, suggesting caspase-dependent apoptotic pathway, culminating in PARP-1 cleavage. Together with previous data, these results show the importance of GTN as a pro-apoptotic, preventive and therapeutic agent for IBD and highlight its potential as a chemopreventive agent for colon cancer. - Highlights: • Goniothalamin (GTN) inhibits the development of TNBS-induced colitis in rats. • Moreover, GTN prevents the development of spontaneous colitis in IL-10 deficient mice. • This activity relies on downregulation of TNF-α and upregulation of SIRT-1 expression

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

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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

Modification of nylon-6 fibres by radiation-induced graft polymerisation of vinylbenzyl chloride

International Nuclear Information System (INIS)

Ting, T.M.; Nasef, Mohamed Mahmoud; Hashim, Kamaruddin

2015-01-01

Modification of nylon-6 fibres by radiation-induced graft copolymerisation (RIGP) of vinylbenzyl chloride (VBC) using the preirradiation method was investigated. A number of grafting parameters such as type of solvent, total dose, monomer concentrations, reaction temperature and reaction time were studied to obtain desired degree of grafting (DG). The DG was found to be a function of reaction parameters and achieved a maximum value of 130 wt% at 20 vol% VBC concentration in methanol, 300 kGy dose, 30 °C temperature and 3 h reaction time. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray diffraction (XRD) were employed to evaluate the chemical, morphological and structural changes that occurred in the grafted fibres, respectively. Thermogravimetric analysis (TGA) was also applied to determine the thermal stability, whereas differential scanning calorimeter (DSC) and universal mechanical tester were used to analyse respective thermal and mechanical properties of the grafted fibres. The results of these analyses provide strong evidence for successful grafting of VBC onto nylon-6, and the variation in the properties of the grafted fibres depends on DG. - Highlights: • Modification of nylon-6 fibres by radiation induced grafting of VBC in methanol. • Establishment of relations between DG and reaction parameters. • Evidence of VBC grafting was provided by FTIR, SEM, XRD, DSC and TGA. • The properties of VBC-grafted nylon-6 fibres depend on DG. • Amendable VBC-grafted nylon-6 fibres retain favourable properties

Therapeutic action of ghrelin in a mouse model of colitis.

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Gonzalez-Rey, Elena; Chorny, Alejo; Delgado, Mario

2006-05-01

Ghrelin is a novel growth hormone-releasing peptide with potential endogenous anti-inflammatory activities ameliorating some pathologic inflammatory conditions. Crohn's disease is a chronic debilitating disease characterized by severe T helper cell (Th)1-driven inflammation of the colon. The aim of this study was to investigate the therapeutic effect of ghrelin in a murine model of colitis. We examined the anti-inflammatory action of ghrelin in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid. Diverse clinical signs of the disease were evaluated, including weight loss, diarrhea, colitis, and histopathology. We also investigated the mechanisms involved in the potential therapeutic effect of ghrelin, such as inflammatory cytokines and chemokines, Th1-type response, and regulatory factors. Ghrelin ameliorated significantly the clinical and histopathologic severity of the trinitrobenzene sulfonic acid-induced colitis; abrogating body weight loss, diarrhea, and inflammation; and increasing survival. The therapeutic effect was associated with down-regulation of both inflammatory and Th1-driven autoimmune response through the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of interluekin-10/transforming growth factor-beta1-secreting regulatory T cells in this therapeutic effect was demonstrated. Importantly, the ghrelin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease. Our data demonstrate novel anti-inflammatory actions for ghrelin in the gastrointestinal tract, ie, the capacity to deactivate the intestinal inflammatory response and to restore mucosal immune tolerance at multiple levels. Consequently, ghrelin administration represents a novel possible therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis.

Immune-Mediated Neutropenia and Thrombocytopenia in a Patient with Ulcerative Colitis: An Unusual Hematological Association with IBD

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Young-In Kim

1995-01-01

Full Text Available Hematological manifestations of inflammatory bowel disease (IBD are well described in the literature. However, the combination of immune-mediated neutropenia and thrombocytopenia has only been reported once in association with IBD. A case is reported of immune-mediated neutropenia and thrombocytopenia in a patient with ulcerative colitis during a relapse. No obvious causes of these hematological abnormalities were found in the patient despite an exhaustive search. An immune-mediated process was confirmed by positive antineutrophil antibody and platelet-associated antibody in the patient’s serum, and the demonstration of binding of the patient’s immunoglobulin G to autologous neutrophils. The patient was treated with high-dose steroid, intravenous gamma-globulin and eventually splenectomy. The platelet count subsequently normalized; although the severe neutropenia recurred, it has subsequently improved without further treatment. Although a definitive cause-effect relationship cannot be established, the immune-mediated neutropenia and thrombocytopenia may be an unusual hematological manifestation associated with ulcerative colitis.

New radiation-induced effects in optical fibres feasible for dosimetry

International Nuclear Information System (INIS)

Tomashuk, A.L.; Golant, K.M.; Dianov, E.M.; Nikolin, I.V.; Zakharkin, I.I.; Stepanov, V.A.

1999-01-01

Three new radiation-induced effects in silica optical fibres suitable for dosimetry are proposed: 1) in fibres with a high-OH cladding and a low-OH core, ionizing radiation disrupts the O-H bonds to let hydrogen diffuse into the core. This results in an increase in the OH-group absorption band amplitude, 2) the polymers used to coat optical fibres consist of hydrogen to the extent of about 50 %. Energetic neutrons produce recoil protons in the fibre coating, which can ''stick'' in the core, turn into hydrogen, and enter the glass network in the form of OH-group, and 3) in N-doped silica fibres irradiated with thermal neutrons, the following reaction 7 N 14 ( 0 n 1 , 1 p 1 ) 6 C 14 occurs and produces protons with energy 620 keV. With this energy, propagation length of protons in silica is 7 μm which means that the escape of protons from a 50 μm core is very weak. In fact all 3 effects lead to the irreversible increase in the OH-group absorption bands, which is proportional to the absorbed dose. With the help of these effects, temperature and dose-rate independent measurements of high doses become possible

Efficacy of Bifidobacterium breve NCC2950 against DSS-induced colitis is dependent on bacterial preparation and timing of administration.

Science.gov (United States)

Hayes, C L; Natividad, J M M; Jury, J; Martin, R; Langella, P; Verdu, E F

2014-03-01

Probiotics have been proposed as a therapy for inflammatory bowel disease, but variations in strains, formulations, and protocols used in clinical trials have hindered the creation of guidelines for their use. Thus, preclinical insight into the mechanisms of specific probiotic strains and mode of administration would be useful to guide future clinical trial design. In this study, live, heat inactivated (HI), and spent culture medium preparations of the probiotic Bifidobacterium breve NCC2950 were administered to specific pathogen free C57BL/6 mice before or during colitis, as well as before colitis reactivation. Five days of 3.5% dextran sulphate sodium in drinking water was used to induce colitis. Pretreatment with live B. breve reduced disease severity, myeloperoxidase activity, microscopic damage, cytokine production, interleukin (IL)-12/IL-10 ratio, and lymphocyte infiltration in the colon. B. breve did not attenuate on-going colitis. After acute colitis, disease symptoms were normalised sooner with live and HI B. breve treatment; however, reactivation of colitis was not prevented. These findings indicate that the efficacy of a probiotic to modulate intestinal inflammation is dependent on the formulation as well as state of inflammation when administered. Overall, live B. breve was most efficacious in preventing acute colitis. Live and HI B. breve also promoted recovery from diarrhoea and colon bleeding after a bout of acute colitis.

ERK controls epithelial cell death receptor signalling and cellular FLICE-like inhibitory protein (c-FLIP) in ulcerative colitis

DEFF Research Database (Denmark)

Seidelin, Jakob Benedict; Coskun, Mehmet; Vainer, Ben

2013-01-01

Intestinal epithelial cell (IEC) death signalling through the Fas receptor is impaired in active ulcerative colitis (UC). This is possibly due to the activation of cytoprotective pathways resulting in limitation of the tissue injury secondary to inflammation. We hypothesized that inflammatory...... the resistance to receptor mediated epithelial apoptosis in active UC. Oncogenic c-FLIP could promote propagation of DNA-damaged IECs and contribute to cancer development in UC....

The relationship between critical flux and fibre movement induced by bubbling in a submerged hollow fibre system.

Science.gov (United States)

Wicaksana, F; Fan, A G; Chen, V

2005-01-01

Bubbling has been used to enhance various processes. In this paper we deal with the effect of bubbling on submerged hollow fibre membranes, where bubbling is applied to prevent severe membrane fouling. Previous work with submerged hollow fibres has observed that significant fibre movement can be induced by bubbling and that there is a qualitative relationship between fibre movement and filtration performance. Therefore, the aim of the present research has been to analyse the link between bubbling, fibre movement and critical flux, identified as the flux at which the transmembrane pressure (TMP) starts to rise. Tests were performed on vertical isolated fibres with a model feed of yeast suspension. The fibres were subject to steady bubbling from below. The parameters of interest were the fibre characteristics, such as tightness, diameter and length, as well as feed concentration. The results confirmed that the critical fluxes are affected by the fibre characteristics and feed concentration. Higher critical flux values can be achieved by using loose fibres, smaller diameters and longer fibres. The enhancement is partially linked to fibre movement and this is confirmed by improved performance when fibres are subject to mechanical movement in the absence of bubbling.

Manufacturing and characterisation of SiC-fibre-reinforced copper in heat sink applications

International Nuclear Information System (INIS)

Kimmig, Stefan

2013-01-01

necessary fibre volume ratio and hence increases the heat conductivity of the CuMMC. The fibre strength was validated by single fibre tension tests. Furthermore, a good bonding between fibre and matrix is necessary to optimize the fibre reinforcement, which is based on load transfer between fibre and matrix. Therefore, both fibre types were coated with interlayer systems and the effectiveness of the bonding was validated by single fibre push-outtests. For those cases where fibre strength and bonding were sufficient, a unidirectional fibre reinforced CuMMC was manufactured, who's mechanical and thermal properties were then characterised. The mechanical tests included tensile tests and strain-controlled cycling tests which gave information about strength, plasticity, hardening and the effect of damage within the CuMMC. To verify that the CuMMC heat sink material achieves the thermal requirements, heat conductivity measurements parallel and perpendicular to the fibre direction were performed. These characterizations were done as a function of fibre volume fraction in the CuMMC and temperature. To investigate the influence of long term exposure to operation temperatures, a heat treatment was carried out for 400 h at 550 C and the mechanical and thermal properties were compared to their initial values. Different optical microscopes and scanning electron microscopes (REM) were used for the analysis of crack surfaces and grindings. For the engineering design of divertor components numerical models of the used material are required. These models need to be developed by adjusting their input parameters to fit experimental results. To that end, strain-controlled cycling tests allowed the analysis of the copper matrix hardening behaviour. This is necessary to understand stress development during operational load cycles of the CuMMC. The comparison of room temperature tests with 300 C tests showed the effects of fabrication-induced residual stress in the CuMMC.

Olanzapine-induced ischemic colitis

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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.

Dietary n-3 polyunsaturated fatty acids (PUFA) decrease obesity-associated Th17 cell-mediated inflammation during colitis.

Science.gov (United States)

Monk, Jennifer M; Hou, Tim Y; Turk, Harmony F; Weeks, Brad; Wu, Chaodong; McMurray, David N; Chapkin, Robert S

2012-01-01

Clinical and experimental evidence suggests that obesity-associated inflammation increases disease activity during colitis, attributed in part to the effects of Th17 cells. Using a model of concurrent obesity and colitis, we monitored changes in critical immune cell subsets and inflammatory biomarker expression in three key tissues: visceral adipose tissue, colon (local inflammatory site) and spleen (systemic inflammatory site), and we hypothesized that n-3 PUFA would reduce the percentage of inflammatory immune cell subsets and suppress inflammatory gene expression, thereby improving the disease phenotype. Obesity was induced in C57BL/6 mice by feeding a high fat (HF) diet (59.2% kcal) alone or an isocaloric HF diet supplemented with fish oil (HF-FO) for 12 weeks. Colitis was induced via a 2.5% trinitrobenzene sulfonic acid (TNBS) enema. The HF-FO diet improved the obese phenotype by reducing i) serum hormone concentrations (leptin and resistin), ii) adipose tissue mRNA expression of inflammatory cytokines (MCP-1, IFNγ, IL-6, IL17F and IL-21) and iii) total (F4/80⁺ CD11b⁺) and inflammatory adipose tissue M1 (F4/80⁺ CD11c⁺) macrophage content compared to HF (Pdiet reduced both colitis-associated disease severity and colonic mRNA expression of the Th17 cell master transcription factor (RORγτ) and critical cytokines (IL-6, IL-17A, IL-17F, IL-21, IL-23 and IFNγ) versus HF (P<0.05). Compared to HF, the percentage of both splenic Th17 and Th1 cells were reduced by the HF-FO group (P<0.05). Under ex vivo polarizing conditions, the percentage of HF-FO derived CD4⁺ T cells that reached Th17 cell effector status was suppressed (P = 0.05). Collectively, these results indicate that n-3 PUFA suppress Th1/Th17 cells and inflammatory macrophage subsets and reconfigure the inflammatory gene expression profile in diverse tissue sites in obese mice following the induction of colitis.

Human umbilical cord mesenchymal stem cells ameliorate mice trinitrobenzene sulfonic acid (TNBS)-induced colitis.

Science.gov (United States)

Liang, Lu; Dong, Chunlan; Chen, Xiaojun; Fang, Zhihong; Xu, Jie; Liu, Meng; Zhang, Xiaoguang; Gu, Dong Sheng; Wang, Ding; Du, Weiting; Zhu, Delin; Han, Zhong Chao

2011-01-01

Mesenchymal stem cells (MSCs), which are poorly immunogenic and have potent immunosuppressive activities, have emerged as a promising candidate for cellular therapeutics for the treatment of disorders caused by abnormal immune responses. In this study we investigated whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could ameliorate colitis in a trinitrobenzene sulfonic acid (TNBS)-induced colitis model. TNBS-treated colitic mice were infused with hUC-MSCs or vehicle control. The mice were sacrificed on day 1, 3, and 5 after infusion, and their clinical and pathological conditions were evaluated by body weight, colon length, and histological analysis. The expression levels of proinflammatory cytokine proteins in colon were examined by ELISA. The homing of hUC-MSCs was studied by live in vivo imaging and immunofluorescent microscopy. hUC-MSCs were found to migrate to the inflamed colon and effectively treated the colitic mice with improved clinical and pathological signs. The levels of IL-17 and IL-23 as well as IFN-γ and IL-6 were significantly lower in the colon tissues of the hUC-MSC-treated mice in comparison with the vehicle-treated mice. Coculture experiments showed that hUC-MSCs not only could inhibit IFN-γ expression but also significantly inhibit IL-17 production by lamina propria mononuclear cells (LPMCs) or splenocytes of the colitic mice or by those isolated from normal animals and stimulated with IL-23. Systemically infused hUC-MSCs could home to the inflamed colon and effectively ameliorate colitis. In addition to the known suppressive effects on Th1-type immune responses, hUC-MSC-mediated modulation of IL-23/IL-17 regulated inflammatory reactions also plays an important role in the amelioration of colitis.

Distinct Immunomodulatory Effects of Spermine Oxidase in Colitis Induced by Epithelial Injury or Infection

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Alain P. Gobert

2018-06-01

Full Text Available Polyamines have been implicated in numerous biological processes, including inflammation and carcinogenesis. Homeostatic regulation leads to interconversion of the polyamines putrescine and the downstream metabolites spermidine and spermine. The enzyme spermine oxidase (SMOX, which back-converts spermine to spermidine, contributes to regulation of polyamine levels, but can also have other effects. We have implicated SMOX in gastric inflammation and carcinogenesis due to infection by the pathogen Helicobacter pylori. In addition, we reported that SMOX can be upregulated in humans with inflammatory bowel disease. Herein, we utilized Smox-deficient mice to examine the role of SMOX in two murine colitis models, Citrobacter rodentium infection and dextran sulfate sodium (DSS-induced epithelial injury. In C. rodentium-infected wild-type (WT mice, there were marked increases in colon weight/length and histologic injury, with mucosal hyperplasia and inflammatory cell infiltration; these changes were ameliorated in Smox−/− mice. In contrast, with DSS, Smox−/− mice exhibited substantial mortality, and increased body weight loss, colon weight/length, and histologic damage. In C. rodentium-infected WT mice, there were increased colonic levels of the chemokines CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL10, and the cytokines IL-6, TNF-α, CSF3, IFN-γ, and IL-17; each were downregulated in Smox−/− mice. In DSS colitis, increased levels of IL-6, CSF3, and IL-17 were further increased in Smox−/− mice. In both models, putrescine and spermidine were increased in WT mice; in Smox−/− mice, the main effect was decreased spermidine and spermidine/spermine ratio. With C. rodentium, polyamine levels correlated with histologic injury, while with DSS, spermidine was inversely correlated with injury. Our studies indicate that SMOX has immunomodulatory effects in experimental colitis via polyamine flux. Thus, SMOX contributes to the immunopathogenesis of

Low cell pH depresses peak power in rat skeletal muscle fibres at both 30 degrees C and 15 degrees C: implications for muscle fatigue.

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Knuth, S T; Dave, H; Peters, J R; Fitts, R H

2006-09-15

Historically, an increase in intracellular H(+) (decrease in cell pH) was thought to contribute to muscle fatigue by direct inhibition of the cross-bridge leading to a reduction in velocity and force. More recently, due to the observation that the effects were less at temperatures closer to those observed in vivo, the importance of H(+) as a fatigue agent has been questioned. The purpose of this work was to re-evaluate the role of H(+) in muscle fatigue by studying the effect of low pH (6.2) on force, velocity and peak power in rat fast- and slow-twitch muscle fibres at 15 degrees C and 30 degrees C. Skinned fast type IIa and slow type I fibres were prepared from the gastrocnemius and soleus, respectively, mounted between a force transducer and position motor, and studied at 15 degrees C and 30 degrees C and pH 7.0 and 6.2, and fibre force (P(0)), unloaded shortening velocity (V(0)), force-velocity, and force-power relationships determined. Consistent with previous observations, low pH depressed the P(0) of both fast and slow fibres, less at 30 degrees C (4-12%) than at 15 degrees C (30%). However, the low pH-induced depressions in slow type I fibre V(0) and peak power were both significantly greater at 30 degrees C (25% versus 9% for V(0) and 34% versus 17% for peak power). For the fast type IIa fibre type, the inhibitory effect of low pH on V(0) was unaltered by temperature, while for peak power the inhibition was reduced at 30 degrees C (37% versus 18%). The curvature of the force-velocity relationship was temperature sensitive, and showed a higher a/P(0) ratio (less curvature) at 30 degrees C. Importantly, at 30 degrees C low pH significantly depressed the ratio of the slow type I fibre, leading to less force and velocity at peak power. These data demonstrate that the direct effect of low pH on peak power in both slow- and fast-twitch fibres at near-in vivo temperatures (30 degrees C) is greater than would be predicted based on changes in P(0), and that the

Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage

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Barrett, Caitlyn W.; Reddy, Vishruth K.; Short, Sarah P.; Motley, Amy K.; Lintel, Mary K.; Bradley, Amber M.; Freeman, Tanner; Vallance, Jefferson; Ning, Wei; Parang, Bobak; Poindexter, Shenika V.; Fingleton, Barbara; Chen, Xi; Washington, Mary K.; Wilson, Keith T.; Shroyer, Noah F.; Hill, Kristina E.; Burk, Raymond F.; Williams, Christopher S.

2015-01-01

Patients with inflammatory bowel disease are at increased risk for colon cancer due to augmented oxidative stress. These patients also have compromised antioxidant defenses as the result of nutritional deficiencies. The micronutrient selenium is essential for selenoprotein production and is transported from the liver to target tissues via selenoprotein P (SEPP1). Target tissues also produce SEPP1, which is thought to possess an endogenous antioxidant function. Here, we have shown that mice with Sepp1 haploinsufficiency or mutations that disrupt either the selenium transport or the enzymatic domain of SEPP1 exhibit increased colitis-associated carcinogenesis as the result of increased genomic instability and promotion of a protumorigenic microenvironment. Reduced SEPP1 function markedly increased M2-polarized macrophages, indicating a role for SEPP1 in macrophage polarization and immune function. Furthermore, compared with partial loss, complete loss of SEPP1 substantially reduced tumor burden, in part due to increased apoptosis. Using intestinal organoid cultures, we found that, compared with those from WT animals, Sepp1-null cultures display increased stem cell characteristics that are coupled with increased ROS production, DNA damage, proliferation, decreased cell survival, and modulation of WNT signaling in response to H2O2-mediated oxidative stress. Together, these data demonstrate that SEPP1 influences inflammatory tumorigenesis by affecting genomic stability, the inflammatory microenvironment, and epithelial stem cell functions. PMID:26053663

Protective Effect of Daikenchuto on Dextran Sulfate Sodium-Induced Colitis in Mice

OpenAIRE

Matsunaga, Takaharu; Hashimoto, Shinichi; Yamamoto, Naoki; Kawasato, Ryo; Shirasawa, Tomohiro; Goto, Atsushi; Fujisawa, Koichi; Takami, Taro; Okamoto, Takeshi; Nishikawa, Jun; Sakaida, Isao

2017-01-01

Aim. To investigate the effect of daikenchuto (TJ-100; DKT) for ulcerative colitis (UC) model mouse and assess its anti-inflammatory mechanisms. Methods. We evaluated the effects of DKT on dextran sulfate sodium- (DSS-) induced experimental colitis. First, we assessed the short-term effects of DKT using two groups: 5% DSS group and 5% DSS with DKT group. Colon length; histological scores; and interleukin- (IL-) 10, IL-1?, and tumor necrosis factor-? mRNA expression profiles were analyzed usin...

TNF-a-induced down-regulation of CDX2 suppresses MEP1A expression in colitis

DEFF Research Database (Denmark)

Coskun, Mehmet; Olsen, Anders Krüger; Holm, Thomas Lindebo

2012-01-01

was investigated in colonic biopsies of ulcerative colitis (UC) patients and in dextran sodium sulfate (DSS)-induced colitis. CDX2 protein expression was investigated by immunoblotting and immunohistochemical procedures. CDX2 and MEP1A regulation was examined in TNF-a-treated Caco-2 cells by reverse transcription...

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

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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.

The Mixture of Anemarrhena asphodeloides and Coptis chinensis Attenuates High-Fat Diet-Induced Colitis in Mice.

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Lim, Su-Min; Choi, Hyun-Sik; Kim, Dong-Hyun

2017-01-01

Anemarrhena asphodeloides (AA, family Liliaceae) inhibits macrophage activation by inhibiting IRAK1 phosphorylation and helper T (Th)17 differentiation. Coptis chinensis (CC, family Ranunculaceae), which inhibits macrophage activation by inhibiting the binding of lipopolysaccharide (LPS) on toll-like receptor 4 and inducing regulatory T (Treg) cell differentiation. The mixture of AA and CC (AC-mix) synergistically attenuates 2,4,6-trinitrobenzenesulfonic acid or dextran sulfate sodium-induced colitis in mice by inhibiting NF-[Formula: see text]B activation and regulating Th17/Treg balance. In the present study, we examined the effect of AC-mix on high-fat diet (HFD)-induced colitis in mice, which induced NF-[Formula: see text]B activation and disturbed Th17/Treg balance. Long-term feeding of HFD in mice caused colitis, including increased macroscopic score and myeloperoxidase activity. Oral administration of AC-mix (20[Formula: see text]mg/kg) suppressed HFD-induced myeloperoxidase activity by 68% ([Formula: see text]). Furthermore, treatment with the AC-mix (20[Formula: see text]mg/kg) inhibited HFD-induced activation of NF-[Formula: see text]B and expression of cyclooxygenase-2, inducible NO synthase, interleukin (IL)-17, and tumor necrosis factor-alpha but increased HFD- suppressed expression of IL-10. AC-mix suppressed HFD-induced differentiation into Th17 cells by 46% ([Formula: see text]) and increased HFD-induced differentiation into regulatory T cells 2.2-fold ([Formula: see text]). AC-mix also suppressed the HFD-induced Proteobacteria/Bacteroidetes ratio on the gut microbiota by 48% ([Formula: see text]). These findings suggest that AC-mix can ameliorate HFD-induced colitis by regulating innate and adaptive immunities and correcting the disturbance of gut microbiota.

Modification of flax fibres by radiation induced emulsion graft copolymerization of glycidyl methacrylate

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Moawia, Rihab Musaad; Nasef, Mohamed Mahmoud; Mohamed, Nor Hasimah; Ripin, Adnan

2016-05-01

Flax fibres were modified by radiation induced graft copolymerization of glycidyl methacrylate (GMA) by pre-irradiation method in an emulsion medium. The effect of reaction parameters on the degree of grafting (DOG) such as concentration of bleaching agent, absorbed dose, monomer concentration, temperature and reaction time were investigated. The DOG was found to be dependent on the investigated parameters. The incorporation of poly(GMA) grafts in the bleached flax fibres was confirmed by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The structural and mechanical changes were evaluated by X-ray diffraction (XRD) and mechanical tester, respectively. The results revealed that reacting bleached flax fibres irradiated with 20 kGy with 5% GMA emulsion containing 0.5% polyoxyethylene-sorbitan monolaurate (Tween 20) surfactant at 40 °C for 1 h led to a maximum DOG of 148%. The grafted fibres showed sufficient mechanical strength and hydrophobicity which make them promising precursors for development of adsorbents after appropriate chemical treatments.

Exosomes Derived from Dendritic Cells Treated with Schistosoma japonicum Soluble Egg Antigen Attenuate DSS-Induced Colitis

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Lifu Wang

2017-09-01

Full Text Available Exosomes are 30–150 nm small membrane vesicles that are released into the extracellular medium via cells that function as a mode of intercellular communication. Dendritic cell (DC-derived exosomes modulate immune responses and prevent the development of autoimmune diseases. Moreover, Schistosoma japonicum eggs show modulatory effects in a mouse model of colitis. Therefore, we hypothesized that exosomes derived from DCs treated with S. japonicum soluble eggs antigen (SEA; SEA-treated DC exosomes would be useful for treating inflammatory bowel disease (IBD. Exosomes were purified from the supernatant of DCs treated or untreated with SEA and identified via transmission electron microscopy, western blotting and NanoSight. Acute colitis was induced via the administration of dextran sulfate sodium (DSS in drinking water (5.0%, wt/vol. Treatment with exosomes was conducted via intraperitoneal injection (i.p.; 50 μg per mouse from day 0 to day 6. Clinical scores were calculated based on weight loss, stool type, and bleeding. Colon length was measured as an indirect marker of inflammation, and colon macroscopic characteristics were determined. Body weight loss and the disease activity index of DSS-induced colitis mice decreased significantly following treatment with SEA-treated DC exosomes. Moreover, the colon lengths of SEA-treated DC exosomes treated colitis mice improved, and their mean colon macroscopic scores decreased. In addition, histologic examinations and histological scores showed that SEA-treated DC exosomes prevented colon damage in acute DSS-induced colitis mice. These results indicate that SEA-treated DC exosomes attenuate the severity of acute DSS-induced colitis mice more effectively than DC exosomes. The current work suggests that SEA-treated DC exosomes may be useful as a new approach to treat IBD.

Reactive oxygen species and fatigue-induced prolonged low-frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing mice.

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Bruton, Joseph D; Place, Nicolas; Yamada, Takashi; Silva, José P; Andrade, Francisco H; Dahlstedt, Anders J; Zhang, Shi-Jin; Katz, Abram; Larsson, Nils-Göran; Westerblad, Håkan

2008-01-01

Skeletal muscle often shows a delayed force recovery after fatiguing stimulation, especially at low stimulation frequencies. In this study we focus on the role of reactive oxygen species (ROS) in this fatigue-induced prolonged low-frequency force depression. Intact, single muscle fibres were dissected from flexor digitorum brevis (FDB) muscles of rats and wild-type and superoxide dismutase 2 (SOD2) overexpressing mice. Force and myoplasmic free [Ca(2+)] ([Ca(2+)](i)) were measured. Fibres were stimulated at different frequencies before and 30 min after fatigue induced by repeated tetani. The results show a marked force decrease at low stimulation frequencies 30 min after fatiguing stimulation in all fibres. This decrease was associated with reduced tetanic [Ca(2+)](i) in wild-type mouse fibres, whereas rat fibres and mouse SOD2 overexpressing fibres instead displayed a decreased myofibrillar Ca(2+) sensitivity. The SOD activity was approximately 50% lower in wild-type mouse than in rat FDB muscles. Myoplasmic ROS increased during repeated tetanic stimulation in rat fibres but not in wild-type mouse fibres. The decreased Ca(2+) sensitivity in rat fibres could be partially reversed by application of the reducing agent dithiothreitol, whereas the decrease in tetanic [Ca(2+)](i) in wild-type mouse fibres was not affected by dithiothreitol or the antioxidant N-acetylcysteine. In conclusion, we describe two different causes of fatigue-induced prolonged low-frequency force depression, which correlate to differences in SOD activity and ROS metabolism. These findings may have clinical implications since ROS-mediated impairments in myofibrillar function can be counteracted by reductants and antioxidants, whereas changes in SR Ca(2+) handling appear more resistant to interventions.

Dietary n-3 polyunsaturated fatty acids (PUFA decrease obesity-associated Th17 cell-mediated inflammation during colitis.

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Jennifer M Monk

Full Text Available Clinical and experimental evidence suggests that obesity-associated inflammation increases disease activity during colitis, attributed in part to the effects of Th17 cells. Using a model of concurrent obesity and colitis, we monitored changes in critical immune cell subsets and inflammatory biomarker expression in three key tissues: visceral adipose tissue, colon (local inflammatory site and spleen (systemic inflammatory site, and we hypothesized that n-3 PUFA would reduce the percentage of inflammatory immune cell subsets and suppress inflammatory gene expression, thereby improving the disease phenotype. Obesity was induced in C57BL/6 mice by feeding a high fat (HF diet (59.2% kcal alone or an isocaloric HF diet supplemented with fish oil (HF-FO for 12 weeks. Colitis was induced via a 2.5% trinitrobenzene sulfonic acid (TNBS enema. The HF-FO diet improved the obese phenotype by reducing i serum hormone concentrations (leptin and resistin, ii adipose tissue mRNA expression of inflammatory cytokines (MCP-1, IFNγ, IL-6, IL17F and IL-21 and iii total (F4/80⁺ CD11b⁺ and inflammatory adipose tissue M1 (F4/80⁺ CD11c⁺ macrophage content compared to HF (P<0.05. In addition, the HF-FO diet reduced both colitis-associated disease severity and colonic mRNA expression of the Th17 cell master transcription factor (RORγτ and critical cytokines (IL-6, IL-17A, IL-17F, IL-21, IL-23 and IFNγ versus HF (P<0.05. Compared to HF, the percentage of both splenic Th17 and Th1 cells were reduced by the HF-FO group (P<0.05. Under ex vivo polarizing conditions, the percentage of HF-FO derived CD4⁺ T cells that reached Th17 cell effector status was suppressed (P = 0.05. Collectively, these results indicate that n-3 PUFA suppress Th1/Th17 cells and inflammatory macrophage subsets and reconfigure the inflammatory gene expression profile in diverse tissue sites in obese mice following the induction of colitis.

The effect of chemically induced colitis, psychological stress and their combination on visceral pain in female Wistar rats.

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Deiteren, Annemie; Vermeulen, Wim; Moreels, Tom G; Pelckmans, Paul A; De Man, Joris G; De Winter, Benedicte Y

2014-09-01

Visceral sensitivity is of pathophysiological importance in abdominal pain disorders and can be modulated by inflammation and stress. However, it is unclear whether inflammation and stress alter visceral perception independently of each other or in conjunction through neuroendocrine interactions. Therefore, we compared the short- and long-term effects of experimental colitis and water avoidance stress (WAS), alone or in combination, on visceral sensitivity in female Wistar rats. Colitis was induced by trinitrobenzene sulfonic acid (TNBS) and colonoscopically confirmed. During WAS, rats were placed on a platform surrounded by water for 1 h. Visceral sensitivity was assessed by quantifying the visceromotor responses (VMRs) to colorectal distension. Activation of the hypothalamic-pituitary-adrenal axis was determined by measuring serum corticosterone in a separate protocol. TNBS instillation resulted in overt colitis, associated with significant visceral hypersensitivity during the acute inflammatory phase (3 days post-TNBS; n = 8/group); after colitis had subsided (28 days post-TNBS), hypersensitivity was resolved (n = 4-8/group). Single WAS was associated with increased VMRs of a magnitude comparable to acute TNBS-induced hypersensitivity (n = 8/group). However, after repetitive WAS no significant hypersensitivity was present (n = 8/group). No additive effect of colitis and stress was seen on visceral pain perception (n = 6-8/group). Corticosterone levels were only increased in acute TNBS-colitis, acute WAS and their combination. To conclude, both colitis and stress successfully induced short-term visceral hypersensitivity and activated the hypothalamic-pituitary-adrenal axis, but long-term effects were absent. In addition, our current findings do not support an additive effect of colitis and stress on visceral sensitivity in female Wistar rats.

Sickle cell-induced ischemic colitis.

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Stewart, Camille L; Ménard, Geraldine E

2009-07-01

Sickle cell-induced ischemic colitis is a rare yet potentially fatal complication of sickle cell anemia. Frequent pain crises with heavy analgesia may obscure and prolong this important diagnosis. Our patient was a 29-year-old female with sickle cell disease who was admitted with left lower quadrant abdominal pain. A diagnostic workup, including chemistries, complete blood count, blood cultures, chest x-ray, computerized tomography scanning, and colonoscopy, was performed to identify the etiology of her symptoms. This case highlights the importance of differentiating simple pain crisis from more serious and life-threatening ischemic bowel. A review of the literature compares this case to others reported and gives a method for diagnosing and treating this complication of sickle cell disease.

Pain hypersensitivity in congenital blindness is associated with faster central processing of C-fibre input

DEFF Research Database (Denmark)

Slimani, H.; Plaghki, L.; Ptito, M.

2016-01-01

Background We have recently shown that visual deprivation from birth exacerbates responses to painful thermal stimuli. However, the mechanisms underlying pain hypersensitivity in congenital blindness are unclear. Methods To study the contribution of Aδ- and C-fibres in pain perception, we measure...... The increased sensitivity to painful thermal stimulation in congenital blindness may be due to more efficient central processing of C-fibre–mediated input, which may help to avoid impending dangerous encounters with stimuli that threaten the bodily integrity....

Obesogenic diet-induced gut barrier dysfunction and pathobiont expansion aggravate experimental colitis.

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June-Chul Lee

Full Text Available Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease.

Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage-Associated Inflammatory Responses.

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Qi Ying Lean

Full Text Available Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS. Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8, colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis.

Microwave-assisted ionic liquid-mediated rapid catalytic conversion of non-edible lignocellulosic Sunn hemp fibres to biofuels.

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Paul, Souvik Kumar; Chakraborty, Saikat

2018-04-01

Sunn hemp fibre - a cellulose-rich crystalline non-food energy crop, containing 75.6% cellulose, 10.05% hemicellulose, 10.32% lignin, with high crystallinity (80.17%) and degree of polymerization (650) - is identified as a new non-food substrate for lignocellulosic biofuel production. Microwave irradiation is employed to rapidly rupture the cellulose's glycosidic bonds and enhance glucose yield to 78.7% at 160 °C in only 46 min. The reactants - long-chain cellulose, ionic liquid, transition metal catalyst, and water - form a polar supramolecular complex that rotates under the microwave's alternating polarity and rapidly dissipates the electromagnetic energy through molecular collisions, thus accelerating glycosidic bond breakage. In 46 min, 1 kg of Sunn hemp fibres containing 756 g of cellulose produces 595 g of glucose at 160 °C, and 203 g of hydroxymethyl furfural (furanic biofuel precursor) at 180 °C. Yeast mediated glucose fermentation produces 75.6% bioethanol yield at 30 °C, and the ionic liquid is recycled for cost-effectiveness. Copyright © 2018 Elsevier Ltd. All rights reserved.

Exercise-induced metallothionein expression in human skeletal muscle fibres

DEFF Research Database (Denmark)

Penkowa, Milena; Keller, Pernille; Keller, Charlotte

2005-01-01

in both type I and II muscle fibres. This is the first report demonstrating that MT-I + II are significantly induced in human skeletal muscle fibres following exercise. As MT-I + II are antioxidant factors that protect various tissues during pathological conditions, the MT-I + II increases post exercise......Exercise induces free oxygen radicals that cause oxidative stress, and metallothioneins (MTs) are increased in states of oxidative stress and possess anti-apoptotic effects. We therefore studied expression of the antioxidant factors metallothionein I and II (MT-I + II) in muscle biopsies obtained...... in response to 3 h of bicycle exercise performed by healthy men and in resting controls. Both MT-I + II proteins and MT-II mRNA expression increased significantly in both type I and II muscle fibres after exercise. Moreover, 24 h after exercise the levels of MT-II mRNA and MT-I + II proteins were still highly...

Modification of flax fibres by radiation induced emulsion graft copolymerization of glycidyl methacrylate

International Nuclear Information System (INIS)

Moawia, Rihab Musaad; Nasef, Mohamed Mahmoud; Mohamed, Nor Hasimah; Ripin, Adnan

2016-01-01

Flax fibres were modified by radiation induced graft copolymerization of glycidyl methacrylate (GMA) by pre-irradiation method in an emulsion medium. The effect of reaction parameters on the degree of grafting (DOG) such as concentration of bleaching agent, absorbed dose, monomer concentration, temperature and reaction time were investigated. The DOG was found to be dependent on the investigated parameters. The incorporation of poly(GMA) grafts in the bleached flax fibres was confirmed by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The structural and mechanical changes were evaluated by X-ray diffraction (XRD) and mechanical tester, respectively. The results revealed that reacting bleached flax fibres irradiated with 20 kGy with 5% GMA emulsion containing 0.5% polyoxyethylene-sorbitan monolaurate (Tween 20) surfactant at 40 °C for 1 h led to a maximum DOG of 148%. The grafted fibres showed sufficient mechanical strength and hydrophobicity which make them promising precursors for development of adsorbents after appropriate chemical treatments. - Highlights: • Flax fibers were modified by radiation induced emulsion grafting of GMA. • Bleaching with 0.7 wt% Na-chlorite was essential for achieving high DOGs. • Effect of reaction parameters on the degree of grafting were established. • The incorporation of poly-GMA grafts was proved by SEM, FTIR and XRD. • The obtained poly-GMA grafted flax fibers have potential for adsorbent making.

G protein-coupled receptor kinase-2-deficient mice are protected from dextran sodium sulfate-induced acute colitis.

Science.gov (United States)

Steury, Michael D; Kang, Ho Jun; Lee, Taehyung; Lucas, Peter C; McCabe, Laura R; Parameswaran, Narayanan

2018-06-01

G protein-coupled receptor kinase 2 (GRK2) is a serine/threonine kinase and plays a key role in different disease processes. Previously, we showed that GRK2 knockdown enhances wound healing in colonic epithelial cells. Therefore, we hypothesized that ablation of GRK2 would protect mice from dextran sodium sulfate (DSS)-induced acute colitis. To test this, we administered DSS to wild-type (GRK2 +/+ ) and GRK2 heterozygous (GRK +/- ) mice in their drinking water for 7 days. As predicted, GRK2 +/- mice were protected from colitis as demonstrated by decreased weight loss (20% loss in GRK2 +/+ vs. 11% loss in GRK2 +/- ). lower disease activity index (GRK2 +/+ 9.1 vs GRK2 +/- 4.1), and increased colon lengths (GRK2 +/+ 4.7 cm vs GRK2 +/- 5.3 cm). To examine the mechanisms by which GRK2 +/- mice are protected from colitis, we investigated expression of inflammatory genes in the colon as well as immune cell profiles in colonic lamina propria, mesenteric lymph node, and in bone marrow. Our results did not reveal differences in immune cell profiles between the two genotypes. However, expression of inflammatory genes was significantly decreased in DSS-treated GRK2 +/- mice compared with GRK2 +/+ . To understand the mechanisms, we generated myeloid-specific GRK2 knockout mice and subjected them to DSS-induced colitis. Similar to whole body GRK2 heterozygous knockout mice, myeloid-specific knockout of GRK2 was sufficient for the protection from DSS-induced colitis. Together our results indicate that deficiency of GRK2 protects mice from DSS-induced colitis and further suggests that the mechanism of this effect is likely via GRK2 regulation of inflammatory genes in the myeloid cells.

Thermal shock behaviour of SiC-fibre-reinforced glasses

International Nuclear Information System (INIS)

Klug, T.; Reichert, J.; Brueckner, R.

1992-01-01

The preparation of two SiC-fibre-reinforced glasses with very different thermal expansion coefficients and glass transition temperatures is described and the influence of long-time temperature and thermal shock behaviour of these composites on the mechanical properties is investigated by means of bending test experiments before and after thermal treatments. It will be shown from experiments and calculations on stresses due to thermal expansion mismatch between fibre and glass matrix that not only best mechanical properties but also best thermal shock behaviour are connected with low tensile intrinsic stresses produced by thermal expansion mismatch during preparation. The thermal shock resistance of the best composite (SiC fibre/DURAN glass) does not show a significant decrease of flexural strength even after 60 shocks from 550 to 25deg C in water, while the bulk glass sample of the same dimension was destroyed by one thermal shock from 350deg C. (orig.) [de

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

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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

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

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

2015-01-01

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

Dietary Heme Induces Gut Dysbiosis, Aggravates Colitis, and Potentiates the Development of Adenomas in Mice

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Marco Constante

2017-09-01

Full Text Available Dietary heme can be used by colonic bacteria equipped with heme-uptake systems as a growth factor and thereby impact on the microbial community structure. The impact of heme on the gut microbiota composition may be particularly pertinent in chronic inflammation such as in inflammatory bowel disease (IBD, where a strong association with gut dysbiosis has been consistently reported. In this study we investigated the influence of dietary heme on the gut microbiota and inferred metagenomic composition, and on chemically induced colitis and colitis-associated adenoma development in mice. Using 16S rRNA gene sequencing, we found that mice fed a diet supplemented with heme significantly altered their microbiota composition, characterized by a decrease in α-diversity, a reduction of Firmicutes and an increase of Proteobacteria, particularly Enterobacteriaceae. These changes were similar to shifts seen in dextran sodium sulfate (DSS-treated mice to induce colitis. In addition, dietary heme, but not systemically delivered heme, contributed to the exacerbation of DSS-induced colitis and facilitated adenoma formation in the azoxymethane/DSS colorectal cancer (CRC mouse model. Using inferred metagenomics, we found that the microbiota alterations elicited by dietary heme resulted in non-beneficial functional shifts, which were also characteristic of DSS-induced colitis. Furthermore, a reduction in fecal butyrate levels was found in mice fed the heme supplemented diet compared to mice fed the control diet. Iron metabolism genes known to contribute to heme release from red blood cells, heme uptake, and heme exporter proteins, were significantly enriched, indicating a shift toward favoring the growth of bacteria able to uptake heme and protect against its toxicity. In conclusion, our data suggest that luminal heme, originating from dietary components or gastrointestinal bleeding in IBD and, to lesser extent in CRC, directly contributes to microbiota dysbiosis

The effect of ileotransversostomy on carrageenan-induced colitis in guinea pigs

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Poulsen, Steen Seier

1983-01-01

By oral administration of degraded carrageenan a colitis-like disease can be induced in guinea pigs which almost exclusively affects the caecum. To study the effect of degraded carrageenan on the distal colon and rectum, an ileotransversostomy was performed. In the non-operated group of animals...

Adrenal-Derived Hormones Differentially Modulate Intestinal Immunity in Experimental Colitis

OpenAIRE

Souza, Patrícia Reis de; Sales-Campos, Helioswilton; Basso, Paulo José; Nardini, Viviani; Silva, Angelica; Banquieri, Fernanda; Alves, Vanessa Beatriz Freitas; Chica, Javier Emílio Lazo; Nomizo, Auro; Cardoso, Cristina Ribeiro de Barros

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...

A membrane glucocorticoid receptor mediates the rapid/non-genomic actions of glucocorticoids in mammalian skeletal muscle fibres.

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Pérez, María Hernández-Alcalá; Cormack, Jonathan; Mallinson, David; Mutungi, Gabriel

2013-10-15

Glucocorticoids (GCs) are steroid hormones released from the adrenal gland in response to stress. They are also some of the most potent anti-inflammatory and immunosuppressive drugs currently in clinical use. They exert most of their physiological and pharmacological actions through the classical/genomic pathway. However, they also have rapid/non-genomic actions whose physiological and pharmacological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the rapid/non-genomic effects of two widely prescribed glucocorticoids, beclomethasone dipropionate (BDP) and prednisolone acetate (PDNA), on force production in isolated, intact, mouse skeletal muscle fibre bundles. The results show that the effects of both GCs on maximum isometric force (Po) were fibre-type dependent. Thus, they increased Po in the slow-twitch fibre bundles without significantly affecting that of the fast-twitch fibre bundles. The increase in Po occurred within 10 min and was insensitive to the transcriptional inhibitor actinomycin D. Also, it was maximal at ∼250 nM and was blocked by the glucocorticoid receptor (GCR) inhibitor RU486 and a monoclonal anti-GCR, suggesting that it was mediated by a membrane (m) GCR. Both muscle fibre types expressed a cytosolic GCR. However, a mGCR was present only in the slow-twitch fibres. The receptor was more abundant in oxidative than in glycolytic fibres and was confined mainly to the periphery of the fibres where it co-localised with laminin. From these findings we conclude that the rapid/non-genomic actions of GCs are mediated by a mGCR and that they are physiologically/therapeutically beneficial, especially in slow-twitch muscle fibres.

Cape Gooseberry [Physalis peruviana L.] Calyces Ameliorate TNBS Acid-induced Colitis in Rats.

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Castro, Jenny; Ocampo, Yanet; Franco, Luis

2015-11-01

Physalis peruviana [cape gooseberry] is highly appreciated for its commercial value. The Colombian ecotype is in great demand in the international market, particularly for the unique morphological characteristics of the calyx, which has extended use as a traditional herbal remedy in Colombia because of its anti-inflammatory properties. In this work, the anti-inflammatory activity of the total ethereal extract of Physalis peruviana calyces was evaluated in preventive and therapeutic protocols in a TNBS acid-induced colitis rat model. Colitis was induced by intrarectal administration of TNBS. An evaluation of macroscopic and histopathological parameters in colonic tissue was performed, along with the determination of myeloperoxidase enzyme activity, cytokine levels and gene expression. Additionally, effects on nitric oxide release by lipopolysaccharide [LPS]-stimulated RAW264.7 macrophages and the scavenging activity of DPPH and ABTS free radicals were determined. The treatment with the Physalis peruviana extract produced a significant improvement in the colonic tissue at both macroscopic and histological levels. IL-1β and TNF-α production was reduced by the extract in both experimental approaches. The groups treated with Physalis peruviana showed a tendency to MUC2 up-regulation and down-regulation of COX-2, iNOS, NLRP3, IL-1β, IL-6 and IL-10 expression. Nitric oxide release in RAW264.7 macrophages was significantly inhibited. The Physalis peruviana extract showed intestinal anti-inflammatory activity in the TNBS-induced colitis model, placing this species' calyx, a natural derivative, as a promising source of metabolites that could be used in treatment for inflammatory bowel disease. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Fibre intake and the development of inflammatory bowel disease

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Andersen, Vibeke; Chan, Simon; Luben, Robert

2018-01-01

Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn's disease [CD] and ulcerative colitis [UC] in a large...... for the development of inflammatory bowel disease. Each case was matched with four controls and odds ratios [ORs] for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed. Results: In total, 104 and 221 participants developed incident CD...

Characterization of T-regulatory cells, induced by immature dendritic cells, which inhibit enteroantigen-reactive colitis-inducing T-cell responses in vitro and in vivo

DEFF Research Database (Denmark)

Gad, Monika; Kristensen, Nanna N; Kury, Evelyn

2004-01-01

-injected into severe combined immunodeficiency (SCID) mice with colitis-inducing CD4(+) CD25(-) T cells. Both unfractionated CD4(+) and purified CD25(+) Treg cells fully protected the recipients against the development of colitis. In contrast, co-transfer of fractionated CD25(-) T cells offered no protection against...

Enhancement of the oxidation resistance of carbon fibres in C/C composites via surface treatments

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Labruquere, S.; Pailler, R.; Naslain, R. [Bordeaux Univ., Pessac (France). Lab. des Composites Thermostructuraux; Desbat, B. [Lab. de Spectroscopie Moleculaire et Cristalline, Univ. of Bordeaux, Talence (France)

1997-12-31

Carbon-carbon (C/C) composites are commonly used in rockets and braking systems. However, the carbon reacts with oxygen, burning away rapidly at temperatures as low as 450 C. This work deals with the protection of carbon fibres from oxidation between 600 and 1000 C. Two kinds of methods were investigated to protect carbon fibres: (i) surface treatment with aqueous solutions (e.g. of H3PO4) and (ii) chemical vapour deposition (CVD) of SiC coatings. Oxidation resistance of the as treated preforms was studied under dry air atmosphere. (orig.) 2 refs.

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

A Limited Role of p53 on the Ability of a Hexane Fraction of American Ginseng to Suppress Mouse Colitis

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Deepak Poudyal

2012-01-01

Full Text Available Ulcerative colitis (UC is debilitating and carries a high colon cancer risk. Apoptosis of inflammatory cells is a key mechanism regulating UC. We have recently shown that American ginseng (AG, and to a greater extent, a Hexane fraction of AG (HAG can cause apoptosis and suppress mouse colitis through a p53-mediated mechanism. Here, we tested the hypothesis that HAG suppresses colitis through a p53 mechanism. We found only a limited impact of p53 in the ability of HAG to induce inflammatory cell apoptosis and suppress mouse colitis in vitro and in vivo. Finally, we asked whether HAG could cause cell cycle arrest of HCT116 colon cancer cells in vitro. Interestingly, HAG caused a G1 arrest of such cells independent of p53 status. Findings are significant because HAG suppresses colitis and associated colon cancer, and mutation in p53 is observed in most colitis-driven colon cancers. Therefore, HAG might be very effective in targeting the inflammatory cells and cancer cells since it induces apoptosis of inflammatory cells and cell cycle arrest in both p53−/− and WT p53 colon cancer cells.

Investigations of plasma induced effects on the surface properties of lignocellulosic natural coir fibres

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Praveen, K.M., E-mail: praveenkmiiucnn@gmail.com [International and Inter University Centre for Nano Science and Nanotechnology (IIUCNN), Mahatma Gandhi University, Kottayam, Kerala (India); Centre de Recherche C.Huygens, LIMATB (Laboratoired’Ingénierie des Matériaux de Bretagne), Université De Bretagne-Sud, Rue stMaudé – BP 92116, Cedex Lorient 56321 Lorient (France); Thomas, Sabu [International and Inter University Centre for Nano Science and Nanotechnology (IIUCNN), Mahatma Gandhi University, Kottayam, Kerala (India); Grohens, Yves [Centre de Recherche C.Huygens, LIMATB (Laboratoired’Ingénierie des Matériaux de Bretagne), Université De Bretagne-Sud, Rue stMaudé – BP 92116, Cedex Lorient 56321 Lorient (France); Mozetič, Miran; Junkar, Ita; Primc, Gregor [Department of Surface Engineering, Jozef Stefan Institute, Jamovacesta 39, Ljubljana 1000 (Slovenia); Gorjanc, Marija [Faculty of Natural Sciences and Engineering, University of Ljubljana, Aškerčeva 12, Ljubljana 1000 (Slovenia)

2016-04-15

Graphical abstract: Plasma induced changes on the morphology of coir fibres (Viewed and Analysed using scanning electron microscopy, Jeol JSM 7600 FEG). The O{sub 2} plasma treated fibre possessed increased hydrophilicity due to the chemical and physical changes induced by plasma. - Highlights: • Plasma-induced effects on the surface properties of lignocellulosic natural coir fibres were investigated. • The morphological study using SEM analysis also confirmed the surface changes which were observed after plasma treatment. • The water absorption studies show an increase of water absorption from 39% to around 100%. • The topographic measurements done using atomic force microscopy (AFM) showed etching of fibre wall, and this is responsible for higher water absorption. • XPS analysis reveals that the oxygen content measured for samples treated at 50 Pa increased from initial 18 at% to about 32 at%. - Abstract: The development of lignocellulosic natural-fibre-reinforced polymers composites are constrained by two limitations: the upper temperature at which the fibre can be processed and the significant differences between the surface energy of the fibre and the polymer matrix. Since the fibres and matrices are chemically different, strong adhesion at their interface is needed for the effective transfer of stress and bond distribution throughout the interface. The present study investigated the plasma induced effects on the surface properties of natural coir fibres. Weakly ionized oxygen plasma was created in two different discharge chambers by an inductively coupled radiofrequency (RF) discharge. The water absorption studies showed an increase of water sorption from 39% to 100%. The morphological study using scanning electron microscopy (SEM) analysis also confirmed the surface changes which were observed after the plasma treatment. The topographic measurements and phase imaging done using atomic force microscopy (AFM) indicated difference in topographic

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

International Nuclear Information System (INIS)

Singh, Udai P.; Singh, Narendra P.; Singh, Balwan; Price, Robert L.; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

2012-01-01

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 −/− mice. JWH-133 effectively attenuated the overall clinical score, and reversed colitis-associated pathogenesis and decrease in body weight in IL-10 −/− mice. After JWH-133 treatment, the percentage of CD4 + 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 toxicity to colon

Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

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Ding, Hao; Liu, Xiao-Chang; Mei, Qiao; Xu, Jian-Ming; Hu, Xiang-Yang; Hu, Jing

2014-04-07

Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.

Crystallization of the C-terminal head domain of the avian adenovirus CELO long fibre

Energy Technology Data Exchange (ETDEWEB)

Guardado Calvo, Pablo [Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Sur, E-15782 Santiago de Compostela (Spain); Llamas-Saiz, Antonio L. [Unidad de Difracción de Rayos X, Laboratorio Integral de Dinámica y Estructura de Biomoléculas José R. Carracido, Edificio CACTUS, Universidad de Santiago de Compostela, Campus Sur, E-15782 Santiago de Compostela (Spain); Langlois, Patrick [Agence Francaise de Securité Sanitaire des Aliments, Unité Génétique Virale et Biosecurité, Site Les Croix, BP 53, F-22440 Ploufragan (France); Raaij, Mark J. van, E-mail: vanraaij@usc.es [Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Sur, E-15782 Santiago de Compostela (Spain); Unidad de Difracción de Rayos X, Laboratorio Integral de Dinámica y Estructura de Biomoléculas José R. Carracido, Edificio CACTUS, Universidad de Santiago de Compostela, Campus Sur, E-15782 Santiago de Compostela (Spain)

2006-05-01

Avian adenovirus long-fibre head trimers were expressed, purified and crystallized. The crystals belong to space group C2 (unit-cell parameters a = 216.5, b = 59.2, c = 57.5 Å, β = 101.3°). A complete highly redundant data set was collected to 2.2 Å resolution at 100 K using a rotating-anode X-ray source. Avian adenovirus CELO contains two different fibres: fibre 1, the long fibre, and fibre 2, the short fibre. The short fibre is responsible for binding to an unknown avian receptor and is essential for infection of birds. The long fibre is not essential, but is known to bind the coxsackievirus and adenovirus receptor protein. Both trimeric fibres are attached to the same penton base, of which each icosahedral virus contains 12 copies. The short fibre extends straight outwards, while the long fibre emerges at an angle. The carboxy-terminal amino acids 579–793 of the avian adenovirus long fibre have been expressed with an amino-terminal hexahistidine tag and the expressed trimeric protein has been purified by nickel-affinity chromatography and crystallized. Crystals were grown at low pH using PEG 10 000 as precipitant and belonged to space group C2. The crystals diffracted rotating-anode Cu Kα radiation to at least 1.9 Å resolution and a complete data set was collected from a single crystal to 2.2 Å resolution. Unit-cell parameters were a = 216.5, b = 59.2, c = 57.5 Å, β = 101.3°, suggesting one trimer per asymmetric unit and a solvent content of 46%. The long fibre head does not have significant sequence homology to any other protein of known structure and molecular-replacement attempts with known fibre-head structures were unsuccessful. However, a map calculated using SIRAS phasing shows a clear trimer with a shape similar to known adenovirus fibre-head structures. Structure solution is in progress.

Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease.

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Hammami, Muhammad Bader; Al-Taee, Ahmad; Meeks, Marshall; Fesler, Mark; Hurley, M Yadira; Cao, Dengfeng; Lai, Jin-Ping

2017-04-01

Idelalisib is a selective inhibitor of the delta isoform of phosphatidylinositol 3-kinase which was approved by the United States Federal Drug Administration in 2014 for the treatment of relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Drug-induced injury of the gastrointestinal tract is a relatively frequent but usually under-recognized disease entity. We report the case of a 56-year-old male with a history of relapsed follicular lymphoma status post allogenic bone marrow transplant who developed severe diarrhea with a skin eruption mimicking graft-versus-host disease (GVHD) 6 months after starting idelalisib. He underwent a colonoscopy demonstrating a grossly normal-appearing colon and terminal ileum. Biopsies taken during the procedure revealed mild active ileitis, colitis, and proctitis with frequent epithelial apoptosis, and focal intra-epithelial lymphocytosis. Skin biopsies revealed sub-acute spongiotic dermatitis suggestive of either contact dermatitis or an eczematous drug reaction. Symptoms were attributed to idelalisib given their resolution with withdrawal of the drug in conjunction with the skin and colonic biopsies. High clinical suspicion and awareness of the histological features of idelalisib-associated colitis is important to distinguish it from potential mimickers such as GVHD and infectious colitis.

Interobserver variability and feasibility of polymerase chain reaction-based assay in distinguishing ischemic colitis from Clostridium difficile colitis in endoscopic mucosal biopsies.

Science.gov (United States)

Wiland, Homer O; Procop, Gary W; Goldblum, John R; Tuohy, Marion; Rybicki, Lisa; Patil, Deepa T

2013-06-01

Polymerase chain reaction (PCR)-based assays using stool samples are currently the most effective method of detecting Clostridium difficile. This study examines the feasibility of this assay using mucosal biopsy samples and evaluates the interobserver reproducibility in diagnosing and distinguishing ischemic colitis from C difficile colitis. Thirty-eight biopsy specimens were reviewed and classified by 3 observers into C difficile and ischemic colitis. The findings were correlated with clinical data. PCR was performed on 34 cases using BD GeneOhm C difficile assay. The histologic interobserver agreement was excellent (κ= 0.86) and the agreement between histologic and clinical diagnosis was good (κ = 0.84). All 19 ischemic colitis cases tested negative (100% specificity) and 3 of 15 cases of C difficile colitis tested positive (20% sensitivity). C difficile colitis can be reliably distinguished from ischemic colitis using histologic criteria. The C difficile PCR test on endoscopic biopsy specimens has excellent specificity but limited sensitivity.

Activation of NF-κB: bridging the gap between inflammation and cancer in colitis-mediated colon carcinogenesis.

Science.gov (United States)

Setia, Shruti; Nehru, Bimla; Sanyal, Sankar Nath

2014-02-01

Several studies have shown the anti-neoplastic effects of non-steroidal anti-inflammatory drugs (NSAIDs) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis, but how these drugs act in case of inflammation-augmented tumorigenesis is still not clear. The present study therefore designs an animal model of colitis-associated colon cancer where 3% Dextran sufate sodium (DSS) is used to develop ulcerative colitis and DMH treatment leads to colon carcinogenesis as early as in six weeks. Clinical symptoms for ulcerative colitis were studied using Disease Activity Index (DAI) while myeloperoxidase assay marked the neutrophil infiltration in DSS and DMH treated groups. The present results indicated the upregulation of the activity of inflammatory marker enzyme, cyclooxygenase-2 (cox-2) and pro-inflammatory cytokines such as TNF-α, IL-1β, IL-4 and IFN-γ with the treatment of DSS as well as DMH. The presence of cytokines in the inflammatory milieu might lead to the transformation of cytoplasmic inactive NF-κB (Nuclear Factor κB) to its active nuclear form, thereby leading to tumorigenesis. The administration of celecoxib along with DSS and DMH, revealed its chemopreventive efficacy in colitis as well as colon cancer. The effect of different doses of DMH on mouse colon was also investigated to obtain a minimum dose of DMH which can induce visible lesions in mice colons at a high incidence. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Sodium 4-phenylbutyrate suppresses the development of dextran sulfate sodium-induced colitis in mice.

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Ono, Kazuhiko; Nimura, Satoshi; Nishinakagawa, Takuya; Hideshima, Yuko; Enjyoji, Munechika; Nabeshima, Kazuki; Nakashima, Manabu

2014-03-01

Sodium 4-phenylbutyrate (PBA) exhibits anti-inflammatory effects by suppressing nuclear factor-κB (NF-κB) activation. In the present study, the effects of PBA on a mouse model of dextran sulfate sodium (DSS)-induced colitis were investigated. The therapeutic efficacy of PBA (150 mg/kg body weight) in DSS-induced colitis was assessed based on the disease activity index (DAI), colon length, the production of inflammatory cytokines and histopathological examination. The results showed an increase in the median survival time in the PBA-treated group compared with that of the untreated DSS control group. DAI scores were lower in the PBA-treated group than in the DSS control group during the 12 days of the experiment. Additionally, PBA treatment inhibited shortening of the colon and the production of the inflammatory cytokines tumor necrosis factor-α, interleukin-1β and IL-6, which were measured in the colonic lavage fluids. Histopathological examination of the DSS control group showed diffused clusters of chronic inflammatory cells infiltrating the lamina propria, partial exfoliation of the surface epithelium and decreased numbers of mature goblet cells. By contrast, in the PBA-treated group the histopathological findings were the same as those of the normal healthy controls. These results suggest that PBA strongly prevents DSS-induced colitis by suppressing the mechanisms involved in its pathogenesis.

Probiotics, fibre and herbal medicinal products for functional and inflammatory bowel disorders

Science.gov (United States)

Ianiro, Gianluca; Pecere, Silvia; Bibbò, Stefano; Cammarota, Giovanni

2016-01-01

Functional bowel disorders (FBD), mainly irritable bowel syndrome (IBS) and functional constipation (FC, also called chronic idiopathic constipation), are very common worldwide. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, although less common, has a strong impact on patients' quality of life, as well as being highly expensive for our healthcare. A definite cure for those disorders is still yet to come. Over the years, several therapeutic approaches complementary or alternative to traditional pharmacological treatments, including probiotics, prebiotics, synbiotics, fibre and herbal medicinal products, have been investigated for the management of both groups of diseases. However, most available studies are biased by several drawbacks, including small samples and poor methodological quality. Probiotics, in particular Saccharomyces boulardii and Lactobacilli (among which Lactobacillus rhamnosus), synbiotics, psyllium, and some herbal medicinal products, primarily peppermint oil, seem to be effective in ameliorating IBS symptoms. Synbiotics and fibre seem to be beneficial in FC patients. The probiotic combination VSL#3 may be effective in inducing remission in patients with mild‐to‐moderate ulcerative colitis, in whom Escherichia coli Nissle 1917 seems to be as effective as mesalamine in maintaining remission. No definite conclusions can be drawn as to the efficacy of fibre and herbal medicinal products in IBD patients due to the low number of studies and the lack of randomized controlled trials that replicate the results obtained in the individual studies conducted so far. Thus, further, well‐designed studies are needed to address the real role of these therapeutic options in the management of both FBD and IBD. Linked Articles This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph

Involvement of PPARγ in the protective action of tropisetron in an experimental model of ulcerative colitis.

Science.gov (United States)

Rahimian, Reza; Zirak, Mohammad Reza; Keshavarz, Mojtaba; Fakhraei, Nahid; Mohammadi-Farani, Ahmad; Hamdi, Hanan; Mousavizadeh, Kazem

2016-09-20

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal (GI) tract. Tropisetron, a selective 5-HT 3 receptor antagonist, is highly used to counteract chemotherapy-induced emesis. Previous studies revealed the anti-inflammatory properties of this drug. The aim of this study was to evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) receptor in the protective effect of tropisetron in an animal model of ulcerative colitis. Experimental colitis was induced by a single intra-colonic instillation of 4% (V/V) acetic acid in male rats. Tropisetron (3 mg/kg) and GW9662 (PPARγ antagonist) (5 mg/kg) were given twice daily for 2 days after colitis induction. Forty-eight hours after induction of colitis, colon was removed and macroscopic and microscopic features were given. Moreover, colonic concentrations of malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels, myeloperoxidase (MPO), and PPARγ activity were assessed. Both macroscopic and histopathological features of colonic injury were markedly ameliorated by tropisetron. Likewise, levels of NO, MDA, TNF-α, and IL-1β diminished significantly (p < .05). GW9662 reversed the effect of tropisetron on these markers partially or completely. In addition, tropisetron increased the PPARγ and decreased the MPO activity (p < .05). Tropisetron exerts notable anti-inflammatory effects in acetic acid-induced colitis in rats, which is probably mediated through PPARγ receptors.

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

Orally administered sodium 4-phenylbutyrate suppresses the development of dextran sulfate sodium-induced colitis in mice.

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Ono, Kazuhiko; Nimura, Satoshi; Hideshima, Yuko; Nabeshima, Kazuki; Nakashima, Manabu

2017-12-01

Sodium 4-phenylbutyrate (PBA) exerts therapeutic effects in a wide range of pathologies. A previous study by the present authors revealed that intraperitoneal administration of PBA suppresses the onset of dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, the effects of orally administered PBA are investigated, as this route of administration is more clinically relevant. The therapeutic efficacy of PBA (10 mg/12 h) in mice with experimental colitis was assessed based on the disease activity index, production of inflammatory cytokines, colon length and histopathological investigations. The results of the present study demonstrated a significantly higher survival rate in the PBA-treated group compared with the PBA-untreated (DSS control) group (P=0.0156). PBA treatment improved pathological indices of experimental colitis (P<0.05). Furthermore, the oral administration of PBA significantly inhibited the DSS-induced shortening of the colon (P<0.05) and overproduction of interleukin (IL)-1β and IL-6 (both P<0.05) as measured in colonic lavage fluids. A marked attenuation of the DSS-induced overproduction of tumor necrosis factor was also observed. For histopathological analysis, a marked decrease in mature goblet cells and increase in enlarged nuclei of the absorptive cells was observed in colon lesions of DSS control mice as compared with normal untreated mice. However, in the PBA-treated mice, no such lesions were observed and the mucosa resembled that of DSS-untreated mice. The results of the present study, combined with those results of a previous study, suggest that oral and intraperitoneal administration of PBA have similar preventative effects on DSS-induced colitis, achieved by suppressing its pathogenesis.

Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

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Kirchgessner Annette

2011-08-01

Full Text Available Abstract Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell.

Lateral stress-induced propagation characteristics in photonic crystal fibres

Institute of Scientific and Technical Information of China (English)

Tian Hong-Da; Yu Zhong-Yuan; Han Li-Hong; Liu Yu-Min

2009-01-01

Using the finite element method, this paper investigates lateral stress-induced propagation characteristics in a pho-tonic crystal fibre of hexagonal symmetry. The results of simulation show the strong stress dependence of effective index of the fundamental guided mode, phase modal birefringence and confinement loss. It also finds that the contribution of the geometrical effect that is related only to deformation of the photonic crystal fibre and the stress-related contribution to phase modal birefringence and confinement loss are entirely different. Furthermore, polarization-dependent stress sensitivity of confinement loss is proposed in this paper.

Loss of PACS-2 delays regeneration in DSS-induced colitis but does not affect the ApcMin model of colorectal cancer

DEFF Research Database (Denmark)

Dombernowsky, Sarah L.; Schwarz, Jeanette; Samsøe-Petersen, Jacob

2017-01-01

in these processes. Specifically, we analyzed the role of Pacs2- deficiency in a DSS-induced colitis model as well as in the genetic ApcMin colon cancer model. We now report that loss of PACS-2 delays tissue regeneration after colonic injury with little effect on key inflammatory parameters. We did however...... not observe any apparent effects on tumor formation driven by excessive proliferative signaling downstream from APC-deficiency. Our findings reveal that the role of PACS- 2 in regulating ADAM17-mediated shedding is not an obligate requirement for the epithelium to respond to the strong inflammatory...

Allicin Alleviates Dextran Sodium Sulfate- (DSS- Induced Ulcerative Colitis in BALB/c Mice

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Ashok Kumar Pandurangan

2015-01-01

Full Text Available The objective of this study is to evaluate the effect of allicin (10 mg/kg body weight, orally in an experimental murine model of UC by administering 2.5% dextran sodium sulfate (DSS in drinking water to BALB/c mice. DSS-induced mice presented reduced body weight, which was improved by allicin administration. We noted increases in CD68 expression, myeloperoxidase (MPO activities, and Malonaldehyde (MDA and mRNA levels of proinflammatory cytokines, such as tumor necrosis factor- (TNF- α, interleukin- (IL- 1β, IL-6, and IL-17, and decrease in the activities of enzymic antioxidants such as superoxide dismutase (SOD, Catalase (CAT, Glutathione reductase (GR, and Glutathione peroxidase (GPx in DSS-induced mice. However, allicin treatment significantly decreased CD68, MPO, MDA, and proinflammatory cytokines and increased the enzymic antioxidants significantly (P<0.05. In addition, allicin was capable of reducing the activation and nuclear accumulation of signal transducer and activator of transcription 3 (STAT3, thereby preventing degradation of the inhibitory protein IκB and inducing inhibition of the nuclear translocation of nuclear factor (NF-κB-p65 in the colonic mucosa. These findings suggest that allicin exerts clinically useful anti-inflammatory effects mediated through the suppression of the NF-κB and IL-6/p-STAT3Y705 pathways.

No Ameliorating Effect of Surfactant Protein D on DSS-Induced Colitis in Mice

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Nexøe, Anders Bathum; Pilecki, Bartosz; Husby, Steffen

Inflammatory bowel diseases (IBD) are disorders associated to a pathological immune response. Surfactant protein D (SP-D) is part of the innate host defense and has known anti-inflammatory effects. We hypothesize that SP-D dampens dextran sodium sulfate (DSS)-induced colitis by reducing innate...

Apple polyphenols extract (APE) improves colon damage in a rat model of colitis.

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D'Argenio, Giuseppe; Mazzone, Giovanna; Tuccillo, Concetta; Ribecco, Maria T; Graziani, Giulia; Gravina, Antonietta G; Caserta, Sergio; Guido, Stefano; Fogliano, Vincenzo; Caporaso, Nicola; Romano, Marco

2012-07-01

Searching for alternative therapies that are effective, safe and less expensive of those currently used for ulcerative colitis, we investigated the efficacy of a polyphenol extract from apple in rat colitis. Rats with trinitrobenzensulphonic acid-induced colitis were treated daily with rectal administration of apple polyphenols 10(-4) M for 14 days. COX-2, TNF-α, tissue transglutaminase and calpain in colon mucosa samples were assessed by reverse transcription-polymerase chain reaction and western blot analyses. To ascertain the role of tissue transglutaminase in mucosal healing, wounded rat fibroblasts were incubated with cystamine (a tissue transglutaminase activity inhibitor). Colitis was associated with increased COX-2, TNF-α, calpain, and tissue transglutaminase mRNA. The protein expression of COX-2, TNF-α and calpain was increased whilst tissue transglutaminase was decreased. Apple extract treatment reduced the severity of colitis (pApple polyphenols reduced the degradation of tissue transglutaminase protein occurring through calpain action. Apple polyphenols-treated wounded fibroblast recovered within 24h showing intense immunoreactivity for tissue transglutaminase. The efficacy of apple extract is mediated by its effects on COX-2 and TNF-α. The unbalance between calpain and tissue transglutaminase may play a role in colonic damage and future therapeutic interventions in ulcerative colitis can target this mechanisms. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Sequestering HMGB1 via DNA-Conjugated Beads Ameliorates Murine Colitis

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Antoine, Daniel J.; Dancho, Meghan; Tsaava, Teá; Li, Jianhua; Lu, Ben; Levine, Yaakov A.; Stiegler, Andrew; Tamari, Yehuda; Al-Abed, Yousef; Roth, Jesse; Tracey, Kevin J.; Yang, Huan

2014-01-01

Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract that affects millions of people worldwide. Although the etiology of IBD is not clear, it is known that products from stressed cells and enteric microbes promote intestinal inflammation. High mobility group box 1 (HMGB1), originally identified as a nuclear DNA binding protein, is a cytokine-like protein mediator implicated in infection, sterile injury, autoimmune disease, and IBD. Elevated levels of HMGB1 have been detected in inflamed human intestinal tissues and in feces of IBD patients and mouse models of colitis. Neutralizing HMGB1 activity by administration of anti-HMGB1 antibodies or HMGB1-specific antagonist improves clinical outcomes in animal models of colitis. Since HMGB1 binds to DNA with high affinity, here we developed a novel strategy to sequester HMGB1 using DNA immobilized on sepharose beads. Screening of DNA-bead constructs revealed that B2 beads, one linear form of DNA conjugated beads, bind HMGB1 with high affinity, capture HMGB1 ex vivo from endotoxin-stimulated RAW 264.7 cell supernatant and from feces of mice with colitis. Oral administration of B2 DNA beads significantly improved body weight, reduced colon injury, and suppressed colonic and circulating cytokine levels in mice with spontaneous colitis (IL-10 knockout) and with dextran sulfate sodium-induced colitis. Thus, DNA beads reduce inflammation by sequestering HMGB1 and may have therapeutic potential for the treatment of IBD. PMID:25127031

C-X-C Chemokine Receptor Type 4 Plays a Crucial Role in Mediating Oxidative Stress-Induced Podocyte Injury.

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Mo, Hongyan; Wu, Qinyu; Miao, Jinhua; Luo, Congwei; Hong, Xue; Wang, Yongping; Tang, Lan; Hou, Fan Fan; Liu, Youhua; Zhou, Lili

2017-08-20

Oxidative stress plays a role in mediating podocyte injury and proteinuria. However, the underlying mechanism remains poorly understood. In this study, we investigated the potential role of C-X-C chemokine receptor type 4 (CXCR4), the receptor for stromal cell-derived factor 1α (SDF-1α), in mediating oxidative stress-induced podocyte injury. In mouse model of adriamycin nephropathy (ADR), CXCR4 expression was significantly induced in podocytes as early as 3 days. This was accompanied by an increased upregulation of oxidative stress in podocyte, as demonstrated by malondialdehyde assay, nitrotyrosine staining and secretion of 8-hydroxy-2'-deoxyguanosine in urine, and induction of NOX2 and NOX4, major subunits of NADPH oxidase. CXCR4 was also induced in human kidney biopsies with proteinuric kidney diseases and colocalized with advanced oxidation protein products (AOPPs), an established oxidative stress trigger. Using cultured podocytes and mouse model, we found that AOPPs induced significant loss of podocyte marker Wilms tumor 1 (WT1), nephrin, and podocalyxin, accompanied by upregulation of desmin both in vitro and in vivo. Furthermore, AOPPs worsened proteinuria and aggravated glomerulosclerosis in ADR. These effects were associated with marked activation of SDF-1α/CXCR4 axis in podocytes. Administration of AMD3100, a specific inhibitor of CXCR4, reduced proteinuria and ameliorated podocyte dysfunction and renal fibrosis triggered by AOPPs in mice. In glomerular miniorgan culture, AOPPs also induced CXCR4 expression and downregulated nephrin and WT1. Innovation and Conclusion: These results suggest that chemokine receptor CXCR4 plays a crucial role in mediating oxidative stress-induced podocyte injury, proteinuria, and renal fibrosis. CXCR4 could be a new target for mitigating podocyte injury, proteinuria, and glomerular sclerosis in proteinuric chronic kidney disease. Antioxid. Redox Signal. 27, 345-362.

Effect of a probiotic beverage consumption (Enterococcus faecium CRL 183 and Bifidobacterium longum ATCC 15707 in rats with chemically induced colitis.

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Larissa Sbaglia Celiberto

Full Text Available Some probiotic strains have the potential to assist in relieving the symptoms of inflammatory bowel disease. The impact of daily ingestion of a soy-based product fermented by Enterococcus faecium CRL 183 and Lactobacillus helveticus 416 with the addition of Bifidobacterium longum ATCC 15707 on chemically induced colitis has been investigated thereof within a period of 30 days.Colitis was induced by dextran sulfate sodium. The animals were randomly assigned into five groups: Group C: negative control; Group CL: positive control; Group CLF: DSS with the fermented product; Group CLP: DSS with the non-fermented product (placebo; Group CLS: DSS with sulfasalazine. The following parameters were monitored: disease activity index, fecal microbial analyses, gastrointestinal survival of probiotic microorganisms and short-chain fatty acids concentration in the feces. At the end of the protocol the animals' colons were removed so as to conduct a macroscopical and histopathological analysis, cytokines and nitrite quantification.Animals belonging to the CLF group showed fewer symptoms of colitis during the induction period and a lower degree of inflammation and ulceration in their colon compared to the CL, CLS and CLP groups (p<0.05. The colon of the animals in groups CL and CLS presented severe crypt damage, which was absent in CLF and CLP groups. A significant increase in the population of Lactobacillus spp. and Bifidobacterium spp. at the end of the protocol was verified only in the CLF animals (p<0.05. This group also showed an increase in short-chain fatty acids (propionate and acetate. Furthermore, the intestinal survival of E. faecium CRL 183 and B. longum ATCC 15707 in the CLF group has been confirmed by biochemical and molecular analyzes.The obtained results suggest that a regular intake of the probiotic product, and placebo to a lesser extent, can reduce the severity of DSS-induced colitis on rats.

Flt3/Flt3L Participates in the Process of Regulating Dendritic Cells and Regulatory T Cells in DSS-Induced Colitis

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Jing-Wei Mao

2014-01-01

Full Text Available The immunoregulation between dendritic cells (DCs and regulatory T cells (T-regs plays an important role in the pathogenesis of ulcerative colitis (UC. Recent research showed that Fms-like tyrosine kinase 3 (Flt3 and Flt3 ligand (Flt3L were involved in the process of DCs regulating T-regs. The DSS-induced colitis model is widely used because of its simplicity and many similarities with human UC. In this study, we observe the disease activity index (DAI and histological scoring, detect the amounts of DCs and T-regs and expression of Flt3/Flt3L, and investigate Flt3/Flt3L participating in the process of DCs regulating T-regs in DSS-induced colitis. Our findings suggest that the reduction of Flt3 and Flt3L expression may possibly induce colonic immunoregulatory imbalance between CD103+MHCII+DCs and CD4+CD25+FoxP3+T-regs in DSS-induced colitis. Flt3/Flt3L participates in the process of regulating DCS and T-regs in the pathogenesis of UC, at least, in the acute stage of this disease.

Perilla frutescens Extracts Protects against Dextran Sulfate Sodium-Induced Murine Colitis: NF-κB, STAT3, and Nrf2 as Putative Targets

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Deung Dae Park

2017-08-01

Full Text Available Perilla frutescens is a culinary and medicinal herb which has a strong anti-inflammatory and antioxidative effects. In the present study, we investigated the effects of Perilla frutescens extract (PE against dextran sulfate sodium (DSS-induced mouse colitis, an animal model that mimics human inflammatory bowel disease (IBD. Five-week-old male ICR mice were treated with a daily dose of PE (20 or 100 mg/kg, p.o. for 1 week, followed by administration of 3% DSS in double distilled drinking water and PE by gavage for another week. DSS-induced colitis was characterized by body weight loss, colon length shortening, diarrhea and bloody stool, and these symptoms were significantly ameliorated by PE treatment. PE administration suppressed DSS-induced expression of proinflammatory enzymes, including cyclooxygenase-2 and inducible nitric oxide synthase as well as cyclin D1, in a dose-dependent fashion. Nuclear factor-kappa B (NF-κB and signal transducer and activator of transcription 3 (STAT3 are major transcriptional regulators of inflammatory signaling. PE administration significantly inhibited the activation of both NF-κB and STAT3 induced by DSS, while it elevated the accumulation of Nrf2 and heme oxygenase-1 in the colon. In another experiment, treatment of CCD841CoN human normal colon epithelial cells with PE (10 mg/ml resulted in the attenuation of the tumor necrosis factor-α-induced expression/activation of mediators of proinflammatory signaling. The above results indicate that PE has a preventive potential for use in the management of IBD.

Perilla frutescens Extracts Protects against Dextran Sulfate Sodium-Induced Murine Colitis: NF-κB, STAT3, and Nrf2 as Putative Targets.

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Dae Park, Deung; Yum, Hye-Won; Zhong, Xiancai; Kim, Seung Hyeon; Kim, Seong Hoon; Kim, Do-Hee; Kim, Su-Jung; Na, Hye-Kyung; Sato, Atsuya; Miura, Takehito; Surh, Young-Joon

2017-01-01

Perilla frutescens is a culinary and medicinal herb which has a strong anti-inflammatory and antioxidative effects. In the present study, we investigated the effects of Perilla frutescens extract (PE) against dextran sulfate sodium (DSS)-induced mouse colitis, an animal model that mimics human inflammatory bowel disease (IBD). Five-week-old male ICR mice were treated with a daily dose of PE (20 or 100 mg/kg, p.o. ) for 1 week, followed by administration of 3% DSS in double distilled drinking water and PE by gavage for another week. DSS-induced colitis was characterized by body weight loss, colon length shortening, diarrhea and bloody stool, and these symptoms were significantly ameliorated by PE treatment. PE administration suppressed DSS-induced expression of proinflammatory enzymes, including cyclooxygenase-2 and inducible nitric oxide synthase as well as cyclin D1, in a dose-dependent fashion. Nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) are major transcriptional regulators of inflammatory signaling. PE administration significantly inhibited the activation of both NF-κB and STAT3 induced by DSS, while it elevated the accumulation of Nrf2 and heme oxygenase-1 in the colon. In another experiment, treatment of CCD841CoN human normal colon epithelial cells with PE (10 mg/ml) resulted in the attenuation of the tumor necrosis factor-α-induced expression/activation of mediators of proinflammatory signaling. The above results indicate that PE has a preventive potential for use in the management of IBD.

Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells.

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Nishida, Atsushi; Nagahama, Kiyotaka; Imaeda, Hirotsugu; Ogawa, Atsuhiro; Lau, Cindy W; Kobayashi, Taku; Hisamatsu, Tadakazu; Preffer, Frederic I; Mizoguchi, Emiko; Ikeuchi, Hiroki; Hibi, Toshifumi; Fukuda, Minoru; Andoh, Akira; Blumberg, Richard S; Mizoguchi, Atsushi

2012-12-17

Immune responses are modified by a diverse and abundant repertoire of carbohydrate structures on the cell surface, which is known as the glycome. In this study, we propose that a unique glycome that can be identified through the binding of galectin-4 is created on local, but not systemic, memory CD4+ T cells under diverse intestinal inflammatory conditions, but not in the healthy state. The colitis-associated glycome (CAG) represents an immature core 1-expressing O-glycan. Development of CAG may be mediated by down-regulation of the expression of core-2 β1,6-N-acetylglucosaminyltransferase (C2GnT) 1, a key enzyme responsible for the production of core-2 O-glycan branch through addition of N-acetylglucosamine (GlcNAc) to a core-1 O-glycan structure. Mechanistically, the CAG seems to contribute to super raft formation associated with the immunological synapse on colonic memory CD4+ T cells and to the consequent stabilization of protein kinase C θ activation, resulting in the stimulation of memory CD4+ T cell expansion in the inflamed intestine. Functionally, CAG-mediated CD4+ T cell expansion contributes to the exacerbation of T cell-mediated experimental intestinal inflammations. Therefore, the CAG may be an attractive therapeutic target to specifically suppress the expansion of effector memory CD4+ T cells in intestinal inflammation such as that seen in inflammatory bowel disease.

Gene expression profiling identifies mechanisms of protection to recurrent trinitrobenzene sulfonic acid colitis mediated by probiotics

NARCIS (Netherlands)

Mariman, R.; Kremer, S.H.A.; Erk, M. van; Lagerweij, T.; Koning, F.; Nagelkerken, L.

2012-01-01

Background: Host-microbiota interactions in the intestinal mucosa play a major role in intestinal immune homeostasis and control the threshold of local inflammation. The aim of this study was to evaluate the efficacy of probiotics in the recurrent trinitrobenzene sulfonic acid (TNBS)-induced colitis

Interleukin 1α-Deficient Mice Have an Altered Gut Microbiota Leading to Protection from Dextran Sodium Sulfate-Induced Colitis.

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Nunberg, Moran; Werbner, Nir; Neuman, Hadar; Bersudsky, Marina; Braiman, Alex; Ben-Shoshan, Moshe; Ben Izhak, Meirav; Louzoun, Yoram; Apte, Ron N; Voronov, Elena; Koren, Omry

2018-01-01

Inflammatory bowel diseases (IBD) are a group of chronic inflammatory disorders of the intestine, with as-yet-unclear etiologies, affecting over a million people in the United States alone. With the emergence of microbiome research, numerous studies have shown a connection between shifts in the gut microbiota composition (dysbiosis) and patterns of IBD development. In a previous study, we showed that interleukin 1α (IL-1α) deficiency in IL-1α knockout (KO) mice results in moderate dextran sodium sulfate (DSS)-induced colitis compared to that of wild-type (WT) mice, characterized by reduced inflammation and complete healing, as shown by parameters of weight loss, disease activity index (DAI) score, histology, and cytokine expression. In this study, we tested whether the protective effects of IL-1α deficiency on DSS-induced colitis correlate with changes in the gut microbiota and whether manipulation of the microbiota by cohousing can alter patterns of colon inflammation. We analyzed the gut microbiota composition in both control (WT) and IL-1α KO mice under steady-state homeostasis, during acute DSS-induced colitis, and after recovery using 16S rRNA next-generation sequencing. Additionally, we performed cohousing of both mouse groups and tested the effects on the microbiota and clinical outcomes. We demonstrate that host-derived IL-1α has a clear influence on gut microbiota composition, as well as on severity of DSS-induced acute colon inflammation. Cohousing both successfully changed the gut microbiota composition and increased the disease severity of IL-1α-deficient mice to levels similar to those of WT mice. This study shows a strong and novel correlation between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. IMPORTANCE Here, we show a connection between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. Specifically, we show that the mild colitis symptoms seen in IL-1�

The effect of Saccharomyces boulardii on human colon cells and inflammation in rats with trinitrobenzene sulfonic acid-induced colitis.

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Lee, Sang Kil; Kim, Youn Wha; Chi, Sung-Gil; Joo, Yeong-Shil; Kim, Hyo Jong

2009-02-01

Saccharomyces boulardii (S. boulardii) has beneficial effects in the treatment of intestinal inflammation; however, little is known about the mechanisms by which these effects occur. We investigated the effects of S. boulardii on the expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and interleukin-8 (IL-8), using human HT-29 colonocytes and a rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. The effect of S. boulardii on gene expression was assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), and Northern blot and Western blot assays. Pharmacological inhibitors for various signaling pathways were used to determine the signaling pathways implicated in the S. boulardii regulation of PPAR-gamma and IL-8. We found that S. boulardii up-regulated and down-regulated PPAR-gamma and IL-8 expression at the transcription level, both in vitro and in vivo (P Saccharomyces boulardii blocked tumor necrosis factor-alpha (TNF-alpha) regulation of PPAR-gamma and IL-8 through disruption of TNF-alpha-mediated nuclear factor kappa B (NF-kappaB) activation. Furthermore, S. boulardii suppressed colitis and expression of pro-inflammatory cytokine genes in vivo (P boulardii reduces colonic inflammation and regulates inflammatory gene expression.

NF-κB mediates the transcription of mouse calsarcin-1 gene, but not calsarcin-2, in C2C12 cells

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Mu Yulian

2007-03-01

Full Text Available Abstract Background The calsarcins comprise a novel family of muscle-specific calcineurin-interaction proteins that play an important role in modulating both the function and substrate specificity of calcineurin in muscle cells. The expression of calsarcin-1 (CS-1 is restricted to slow-twitch skeletal muscle fibres, whereas that of both calsarcin-2 (CS-2 and calsarcin-3 (CS-3 is enriched in fast-twitch fibres. However, the transcriptional control of this selective expression has not been previously elucidated. Results Our real-time RT-PCR analyses suggest that the expression of CS-1 and CS-2 is increased during the myogenic differentiation of mouse C2C12 cells. Promoter deletion analysis further suggests that an NF-κB binding site within the CS-1 promoter is responsible for the up-regulation of CS-1 transcription, but no similar mechanism was evident for CS-2. These findings are further supported by the results of EMSA analysis, as well as by overexpression and inhibition experiments in which NF-κB function was blocked by treatment with its inhibitor, PDTC. In addition, the overexpression of NFATc4 induces both the CS-1 and CS-2 promoters, whereas MEF2C only activates CS-1. Conclusion Our present data suggest that NF-κB is required for the transcription of mouse CS-1 but not CS-2, and that the regulation of the calsarcins is mediated also by the NFAT and MEF2 transcription factors. These results provide new insights into the molecular mechanisms governing transcription in specific muscle fibre cells. The calsarcins may also serve as a valuable mechanistic tool to better understand the regulation of calcineurin signalling during muscle differentiation.

Polymer Optical Fibre Bragg Grating Humidity Sensor at 100ºC

DEFF Research Database (Denmark)

Woyessa, Getinet; Fasano, Andrea; Markos, Christos

2016-01-01

We have demonstrated a polymer optical fibre Bragg grating humidity sensor that can be operated up to 100ºC. The sensor has been fabricated from a polycarbonate (PC) microstructured polymer optical fibre Bragg grating (mPOFBG). PC mPOFBG gave a relative humidity (RH) sensitivity of 6.95±0.83 pm...

CD8 T cells primed in the gut-associated lymphoid tissue induce immune-mediated cholangitis in mice.

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Seidel, Daniel; Eickmeier, Ira; Kühl, Anja A; Hamann, Alf; Loddenkemper, Christoph; Schott, Eckart

2014-02-01

The pathogenesis of primary sclerosing cholangitis (PSC) remains poorly understood. Since PSC predominantly occurs in patients with inflammatory bowel disease, autoimmunity triggered by activated T cells migrating from the gut to the liver is a possible mechanism. We hypothesized that T cells primed in the gut-associated lymphoid tissue (GALT) by a specific antigen migrate to the liver and cause cholangitis when they recognize the same antigen on cholangiocytes. We induced ovalbumin-dependent colitis in mice that express ovalbumin in biliary epithelia (ASBT-OVA mice) and crossed ASBT-OVA mice with mice that express ovalbumin in enterocytes (iFABP-OVA mice). We analyzed T-cell activation in the GALT and crossreactivity to the same antigen in the liver as well as the effects of colitis per se on antigen-presentation and T-cell activation in the liver. Intrarectal application of ovalbumin followed by transfer of CD8 OT-I T cells led to antigen-dependent colitis. CD8 T cells primed in the GALT acquired effector function and the capability to migrate to the liver, where they caused cholangitis in a strictly antigen-dependent manner. Likewise, cholangitis developed in mice expressing ovalbumin simultaneously in biliary epithelia and enterocytes after transfer of OT-I T cells. Dextran sodium sulfate colitis led to increased levels of inflammatory cytokines in the portal venous blood, induced activation of resident liver dendritic cells, and promoted the induction of T-cell-dependent cholangitis. Our data strengthen the notion that immune-mediated cholangitis is caused by T cells primed in the GALT and provide the first link between colitis and cholangitis in an antigen-dependent mouse model. © 2013 by the American Association for the Study of Liver Diseases.

Infliximab induces clinical, endoscopic and histological responses in refractory ulcerative colitis Infliximab induce respuesta clínica, endoscópica e histológica en la colitis ulcerosa refractaria

Directory of Open Access Journals (Sweden)

F. Bermejo

2004-02-01

Full Text Available Background: infliximab is a monoclonal antiTNF-α antibody that has repeatedly shown to be effective in the management of Crohn's disease. However, data are scarce about its efficacy in ulcerative colitis. Aim: to describe the joint experience of three Spanish hospitals in the use of infliximab in patients with active refractory ulcerative colitis. Patients and methods: we present seven cases of ulcerative colitis (6 with chronic active disease despite immunosuppressive therapy, and one with acute steroid-refractory ulcerative colitis treated with infliximab 5 mg/kg of body weight. Clinical response was evaluated by means of the Clinical Activity Index at 2, 4 and 8 weeks after initial infusion. Biochemical (erythrocyte sedimentation rate and C-reactive protein, endoscopic, and histological changes were also assessed. Results: mean age of patients was 45.8 ± 17 years (range 23-77; 4 were female. No adverse effects were recorded. Inflammatory activity diminished significantly in 6 of 7 patients (85.7%; CI 95%: 42-99% both from a clinical (p = 0.01 and biochemical (p Introducción: infliximab, un anticuerpo monoclonal quimérico antiTNF-α ha demostrado su eficacia en pacientes con enfermedad de Crohn. Sin embargo, son escasos los datos sobre su efectividad en el tratamiento de la colitis ulcerosa. Objetivo: describir la experiencia conjunta de 3 hospitales españoles en el uso de infliximab en enfermos con CU activa resistente a otros tratamientos. Pacientes y métodos: se presentan 7 casos de colitis ulcerosa (6 con enfermedad crónicamente activa a pesar de tratamiento con inmunosupresor y 1 con colitis aguda grave refractaria a esteroides tratados con infliximab a dosis de 5 mg/kg de peso. Se evaluó la respuesta clínica mediante un Índice de Actividad Clínica trascurridas 2, 4 y 8 semanas de la infusión inicial. Así mismo, se estudiaron los cambios analíticos (velocidad de sedimentación y proteína C reactiva, endoscópicos e histol

Effect of processed Scutellaria baicalensis on dextran sulfate sodium-induced colitis in mice.

Science.gov (United States)

Choi, Yeon-A; Kang, Ok-Hwa; Park, Hye-Jung; Tae, Jin; Kim, Dae-Ki; Kang, Chon Sik; Choi, Suck-Chei; Yun, Ki-Jung; Choi, Suck-Jun; Nah, Yong-Ho; Kim, Young-Ho; Bae, Ki-Hwan; Lee, Young-Mi

2005-10-01

Scutellaria baicalensis Georgi (Labiatae) has been used in the treatment of inflammatory diseases. Drug processing (Poje) is the process of treating crude drugs by several methods before use. The aim of this study was to determine the effect of processed Scutellaria baicalensis on experimental ulcerative colitis induced by dextran sulfate sodium (DSS). The types of processed Scutellaria baicalensis used in this study were parched Scutellaria baicalensis (PS) and rice wine-baked Scutellaria baicalensis (RWBS). Experimental colitis was induced in mice using a daily treatment of 5% DSS in the drinking water for 7 days. The water extracts of processed Scutellaria baicalensis (1 g/kg) were administered orally once a day for 7 days. The mice were divided in four groups: i) water plus DSS group, ii) crude Scutellaria baicalensis (CS) plus DSS group, iii) PS plus DSS group, and iv) RWBS plus DSS group. RWBS ameliorated all of the inflammatory symptoms, such as body weight loss, rectal bleeding and histological damage, compared to CS. Furthermore, RWBS significantly reduced the mucosal myeloperoxidase activity, and TNF-alpha (tumor necrosis factor-alpha), COX-2 (cyclooxygenase-2), NF-kappaB (nuclear factor-kappa B) and chymase expression more than CS. But these effects were not shown in the PS plus DSS group. Efficacy of Scutellaria baicalensis was increased after rice wine baking, but not after parching. The findings in this study suggest that RWBS may be a useful therapeutic agent for ulcerative colitis.

[Saccharomyces boulardii reduced intestinal inflammation in mice model of 2,4,6-trinitrobencene sulfonic acid induced colitis: based on microarray].

Science.gov (United States)

Lee, Sang Kil; Kim, Hyo Jong; Chi, Sung Gil

2010-01-01

Saccharomyces boulardii has been reported to be beneficial in the treatment of inflammatory bowel disease. The aim of this work was to evaluate the effect of S. boulardii in a mice model of 2,4,6-trinitrobencene sulfonic acid (TNBS) induced colitis and analyze the expression of genes in S. boulardii treated mice by microarray. BALB/c mice received TNBS or TNBS and S. boulardii treatment for 4 days. Microarray was performed on total mRNA form colon, and histologic evaluation was also performed. In mice treated with S. boulardii, the histological appearance and mortality rate were significantly restored compared with rats receiving only TNBS. Among 330 genes which were altered by both S. boulardii and TNBS (>2 folds), 193 genes were down-regulated by S. boulardii in microarray. Most of genes which were down-regulated by S. bouardii were functionally classified as inflammatory and immune response related genes. S. boulardii may reduce colonic inflammation along with regulation of inflammatory and immune responsive genes in TNBS-induced colitis.

Granulocyte-colony-stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis.

Science.gov (United States)

Basso, Lilian; Lapointe, Tamia K; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D; Kurrasch, Deborah M; Altier, Christophe

2017-10-17

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF-induced visceral pain in vivo. Finally, administration of G-CSF-neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron-microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain.

Regeneration of irradiated optical fibres by photo-bleaching?

International Nuclear Information System (INIS)

Henschel, H.; Koehn, O.

1999-01-01

It is known that a light power between 0,1 and 20 μW caused bleaching of colour centres, which implies a reduction of induced loss. Older fibres especially those with a core made of undoped, low OH silica, experience tremendous photo-bleaching. Light of shorter wavelengths has a higher bleaching efficiency than that of longer wavelengths and same light intensity. The investigations have demonstrated that the injection of photo-bleaching light of shorter wavelength and higher intensity can distinctly decrease the radiation-induced loss of Ge-doped fibres, especially at low temperatures. Another possibility to apply photo-bleaching by short wavelength is to regenerate fibres that are permanently installed in radiation environments. Modern undoped multi-mode (MM) step index (Si), Ge-doped MM graded index (Gi) and Ge-doped single-mode (SM) fibres that had been irradiated were submitted to bleaching light. In this article it is shown how loss reduction and necessary bleaching time depend on wavelength and intensity of the bleaching light, on fibre length (bleaching time) and on radiation dose. These results are promising for the regeneration of optical fibres in facilities where the fibres cannot be replaced easily by new ones. (A.C.)

Essential roles of high-mobility group box 1 in the development of murine colitis and colitis-associated cancer

International Nuclear Information System (INIS)

Maeda, Shin; Hikiba, Yohko; Shibata, Wataru; Ohmae, Tomoya; Yanai, Ayako; Ogura, Keiji; Yamada, Shingo; Omata, Masao

2007-01-01

High-mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as a proinflammatory cytokine. We measured the HMGB1 concentration in the sera of mice with chemically induced colitis (DSS; dextran sulfate sodium salt) and found a marked increase. Inhibition of HMGB1 by neutralizing anti-HMGB1 antibody resulted in reduced inflammation in DSS-treated colons. In macrophages, HMGB1 induces several proinflammatory cytokines, such as IL-6, which are regulated by NF-κB activation. Two putative sources of HMGB1 were explored: in one, bacterial factors induce HMGB1 secretion from macrophages and in the other, necrotic epithelial cells directly release HMGB1. LPS induced a small amount of HMGB1 in macrophages, but macrophages incubated with supernatant prepared from necrotic cells and containing large amounts of HMGB1 activated NF-κB and induced IL-6. Using the colitis-associated cancer model, we demonstrated that neutralizing anti-HMGB1 antibody decreases tumor incidence and size. These observations suggest that HMGB1 is a potentially useful target for IBD treatment and the prevention of colitis-associated cancer

Prophylactic role of curcumin in dextran sulfate sodium (DSS)-induced ulcerative colitis murine model.

Science.gov (United States)

Arafa, Hossam M M; Hemeida, Ramadan A; El-Bahrawy, Ali I M; Hamada, Farid M A

2009-06-01

We have addressed in this study the possible protective role of the main principle of turmeric pigment; curcumin on a murine model of ulcerative colitis (UC). Colitis was induced by administration of dextran sulfate sodium (DSS) (3% W/V) in drinking water to male Swiss albino rats for 5 consecutive days. DSS challenge induced UC model that was well characterized morphologically and biochemically. DSS produced shrinkage of colon length and increased the relative colon weight/length ratio accompanied by mucosal edema and bloody stool. Histologically, DSS produced submucosal erosions, ulceration, inflammatory cell infiltration and crypt abscess as well as epithelioglandular hyperplasia. The model was confirmed biochemically, and the test battery entailed elevated serum tumor necrosis factor (TNF-alpha) and colonic activity of myleoperoxidase (MPO). Colonic glutathione-S-transferase (GST) activity and its substrate concentration; GSH, were notably reduced, while lipid peroxidation, expressed as malondialdehyde (MDA) level, and total nitric oxide (NO) were significantly increased. Prior administration of curcumin (100mg/kg, IP) for 7 consecutive days ahead of DSS challenge mitigated the injurious effects of DSS and ameliorated all the altered biochemical parameters. These results suggest that curcumin could possibly have a protective role in ulcerative colitis probably via regulation of oxidant/anti-oxidant balance and modulation of the release of some inflammatory endocoids, namely TNF-alpha and NO.

Anti-colitic effects of kanjangs (fermented soy sauce and sesame sauce) in dextran sulfate sodium-induced colitis in mice.

Science.gov (United States)

Song, Jia-Le; Choi, Jung-Ho; Seo, Jae-Hoon; Lim, Yaung-Iee; Park, Kun-Young

2014-09-01

This study was conducted to investigate the preventive effects of different kanjangs (Korean soy sauces), including acid-hydrolyzed soy sauce (AHSS), fermented soy sauce (FSS), and fermented sesame sauce (FSeS), on 2% dextran sulfate sodium (DSS)-induced ulcerative colitis in C57BL/6J mice. The fermented sauces, particularly FSeS, significantly suppressed DSS-induced body weight loss, increased colon length, and decreased colon weight/length ratios. Histological observations suggested that the fermented sauces prevented edema, mucosal damage, and the loss of crypts induced by DSS compared to the control mice and animals fed AHSS. FSeS and FSS decreased the serum levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6, and IL-17α. mRNA expression of these cytokines as well as that of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in colon mucosa was also inhibited by the two sauces. Our results suggest that fermented sauces, especially FSeS, exert an anticolitic effect partially by reducing the serum levels of proinflammatory cytokines and inhibiting the mRNA expression of these factors in the colon tissue of mice treated with DSS. However, AHSS did not protect against DSS-induced colitis. In addition, low-dose treatment (4 mL/kg) with the fermented sauces resulted in greater anticolitic effects than consumption of a high quantity (8 mL/kg) of the sauces.

CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid mice with colitis

DEFF Research Database (Denmark)

Gad, M; Brimnes, J; Claesson, Mogens Helweg

2003-01-01

Adoptive transfer of CD4+ T cells into scid mice leads to a chronic colitis in the recipients. The transferred CD4+ T cells accumulate in the intestinal lamina propria (LP), express an activated Th1 phenotype and proliferate vigorously when exposed ex vivo to enteric bacterial antigens. As LP CD4......+ T cells from normal BALB/c mice do not respond to enteric bacterial antigens, we have investigated whether colonic LP-derived CD4+ T cells from normal mice suppress the antibacterial response of CD4+ T cells from scid mice with colitis. LP-derived CD4+ T cells cocultured with bone marrow......-derived dendritic cells effectively suppress the antibacterial proliferative response of CD4+ T cells from scid mice with colitis. The majority of these LP T-reg cells display a nonactivated phenotype and suppression is independent of antigen exposure, is partly mediated by soluble factor(s) different from IL-10...

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

). 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...... development of colitis. Suppression was dependent on B cell-derived IL-10, as co-transfer of IL-10 knockout ebx-B cells failed to suppress colitis. Ebx-B cell-mediated suppression of colitis was associated with a decrease in interferon gamma (IFN-¿)-producing T(H) 1 cells and increased frequencies of Foxp3......-expressing T cells. CONCLUSIONS: These data demonstrate that splenic B cells exposed to enterobacterial components acquire immunosuppressive functions by which they can suppress development of experimental T cell-mediated colitis in an IL-10-dependent way. (Inflamm Bowel Dis 2011;)....

Mesalazine-induced myopericarditis in a patient with ulcerative colitis

Directory of Open Access Journals (Sweden)

Jalal Asadi

2017-12-01

Full Text Available A 25-year-old male with a background of ulcerative colitis presented with a two-week history of central chest pain. His ECG on presentation showed global T wave inversion with a peak troponin I of 165 ng/mL. Clinical diagnosis of myopericarditis/myocarditis was made. Echocardiography and cardiac magnetic resonance (MR confirmed the diagnosis. On detailed assessment of his medication history, mesalazine was suspected as an etiological factor, with discontinuation resulting in an improvement in symptoms, inflammatory markers and cardiac enzymes. This is a unique case of mesalazine-induced myopericarditis on a background of inflammatory bowel disease.

SiC fibre by chemical vapour deposition on tungsten filament

Indian Academy of Sciences (India)

Unknown

SiC fibre by chemical vapour deposition on tungsten filament ... CMCs), in defence and industrial applications. SiC has attractive ... porosity along with chemical purity. This is lacking .... reactor. Since mercury is very toxic it should be removed.

Fibre and components induced limitations in high capacity optical networks

DEFF Research Database (Denmark)

Peucheret, Christophe

2003-01-01

The design of future all-optical networks relies on the knowledge of the physical layer transport properties. In this thesis, we focus on two types of system impairments: those induced by the non-ideal transfer functions of optical filters to be found in network elements such as optical add...... design in order to maximise the spectral efficiency in a four add-drop node ring network. The concept of "normalised transmission sections" is introduced in order to ease the dimensioning of transparent domains in future all-optical networks. Normalised sections based on standard single mode fibre (SMF......-drop multiplexers (OADM) and optical cross-connects (OXC), as well as those due to the interaction of group-velocity dispersion, optical fibre non-linearities and accumulation of amplifier noise in the transmission path. The dispersion of fibre optics components is shown to limit their cascadability. Dispersion...

The TRPA1 ion channel is expressed in CD4+ T cells and restrains T-cell-mediated colitis through inhibition of TRPV1.

Science.gov (United States)

Bertin, Samuel; Aoki-Nonaka, Yukari; Lee, Jihyung; de Jong, Petrus R; Kim, Peter; Han, Tiffany; Yu, Timothy; To, Keith; Takahashi, Naoki; Boland, Brigid S; Chang, John T; Ho, Samuel B; Herdman, Scott; Corr, Maripat; Franco, Alessandra; Sharma, Sonia; Dong, Hui; Akopian, Armen N; Raz, Eyal

2017-09-01

Transient receptor potential ankyrin-1 (TRPA1) and transient receptor potential vanilloid-1 (TRPV1) are calcium (Ca 2+ )-permeable ion channels mostly known as pain receptors in sensory neurons. However, growing evidence suggests their crucial involvement in the pathogenesis of IBD. We explored the possible contribution of TRPA1 and TRPV1 to T-cell-mediated colitis. We evaluated the role of Trpa1 gene deletion in two models of experimental colitis (ie, interleukin-10 knockout and T-cell-adoptive transfer models). We performed electrophysiological and Ca 2+ imaging studies to analyse TRPA1 and TRPV1 functions in CD4+ T cells. We used genetic and pharmacological approaches to evaluate TRPV1 contribution to the phenotype of Trpa1 -/- CD4+ T cells. We also analysed TRPA1 and TRPV1 gene expression and TRPA1 + TRPV1 + T cell infiltration in colonic biopsies from patients with IBD. We identified a protective role for TRPA1 in T-cell-mediated colitis. We demonstrated the functional expression of TRPA1 on the plasma membrane of CD4+ T cells and identified that Trpa1 -/- CD4+ T cells have increased T-cell receptor-induced Ca 2+ influx, activation profile and differentiation into Th1-effector cells. This phenotype was abrogated upon genetic deletion or pharmacological inhibition of the TRPV1 channel in mouse and human CD4+ T cells. Finally, we found differential regulation of TRPA1 and TRPV1 gene expression as well as increased infiltration of TRPA1 + TRPV1 + T cells in the colon of patients with IBD. Our study indicates that TRPA1 inhibits TRPV1 channel activity in CD4+ T cells, and consequently restrains CD4+ T-cell activation and colitogenic responses. These findings may therefore have therapeutic implications for human IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

α7 Nicotinic Agonist AR-R17779 Protects Mice against 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in a Spleen-Dependent Way

Directory of Open Access Journals (Sweden)

Andrea Grandi

2017-11-01

Full Text Available The existence of a cholinergic anti-inflammatory pathway negatively modulating the inflammatory and immune responses in various clinical conditions and experimental models has long been postulated. In particular, the protective involvement of the vagus nerve and of nicotinic Ach receptors (nAChRs has been proposed in intestinal inflammation and repeatedly investigated in DSS- and TNBS-induced colitis. However, the role of α7 nAChRs stimulation is still controversial and the potential contribution of α4β2 nAChRs has never been explored in this experimental condition. Our aims were therefore to pharmacologically investigate the role played by both α7 and α4β2 nAChRs in the modulation of the local and systemic inflammatory responses activated in TNBS-induced colitis in mice and to assess the involvement of the spleen in nicotinic responses. To this end, TNBS-exposed mice were sub-acutely treated with various subcutaneous doses of highly selective agonists (AR-R17779 and TC-2403 and antagonists (methyllycaconitine and dihydro-β-erythroidine of α7 and α4β2 nAChRs, respectively, or with sulfasalazine 50 mg/kg per os and clinical and inflammatory responses were evaluated by means of biochemical, histological and flow cytometry assays. α4β2 ligands evoked weak and contradictory effects, while α7 nAChR agonist AR-R17779 emerged as the most beneficial treatment, able to attenuate several local markers of colitis severity and to revert the rise in splenic T-cells and in colonic inflammatory cytokines levels induced by haptenization. After splenectomy, AR-R17779 lost its protective effects, demonstrating for the first time that, in TNBS-model of experimental colitis, the anti-inflammatory effect of exogenous α7 nAChR stimulation is strictly spleen-dependent. Our findings showed that the selective α7 nAChRs agonist AR-R17779 exerted beneficial effects in a model of intestinal inflammation characterized by activation of the adaptive immune

The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

Energy Technology Data Exchange (ETDEWEB)

Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Hidalgo, Cecilia [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Lavandero, Sergio, E-mail: slavander@uchile.cl [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile)

2009-10-09

Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal {alpha}-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

International Nuclear Information System (INIS)

Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo; Hidalgo, Cecilia; Lavandero, Sergio

2009-01-01

Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal α-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

BTB and CNC homolog 1 (Bach1) deficiency ameliorates TNBS colitis in mice: role of M2 macrophages and heme oxygenase-1.

Science.gov (United States)

Harusato, Akihito; Naito, Yuji; Takagi, Tomohisa; Uchiyama, Kazuhiko; Mizushima, Katsura; Hirai, Yasuko; Higashimura, Yasuki; Katada, Kazuhiro; Handa, Osamu; Ishikawa, Takeshi; Yagi, Nobuaki; Kokura, Satoshi; Ichikawa, Hiroshi; Muto, Akihiko; Igarashi, Kazuhiko; Yoshikawa, Toshikazu

2013-01-01

BTB and CNC homolog 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1), which plays an important role in the protection of cells and tissues against acute and chronic inflammation. However, the role of Bach1 in the gastrointestinal mucosal defense system remains little understood. HO-1 supports the suppression of experimental colitis and localizes mainly in macrophages in colonic mucosa. This study was undertaken to elucidate the Bach1/HO-1 system's effects on the pathogenesis of experimental colitis. This study used C57BL/6 (wild-type) and homozygous Bach1-deficient C57BL/6 mice in which colonic damage was induced by the administration of an enema of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Subsequently, they were evaluated macroscopically, histologically, and biochemically. Peritoneal macrophages from the respective mice were isolated and analyzed. Then, wild-type mice were injected with peritoneal macrophages from the respective mice. Acute colitis was induced similarly. TNBS-induced colitis was inhibited in Bach1-deficient mice. TNBS administration increased the expression of HO-1 messenger RNA and protein in colonic mucosa in Bach1-deficient mice. The expression of HO-1 mainly localized in F4/80-immunopositive and CD11b-immunopositive macrophages. Isolated peritoneal macrophages from Bach1-deficient mice highly expressed HO-1 and also manifested M2 macrophage markers, such as Arginase-1, Fizz-1, Ym1, and MRC1. Furthermore, TNBS-induced colitis was inhibited by the transfer of Bach1-deficient macrophages into wild-type mice. Deficiency of Bach1 ameliorated TNBS-induced colitis. Bach1-deficient macrophages played a key role in protection against colitis. Targeting of this mechanism is applicable to cell therapy for human inflammatory bowel disease.

Cytocompatibility and Mechanical Properties of Short Phosphate Glass Fibre Reinforced Polylactic Acid (PLA Composites: Effect of Coupling Agent Mediated Interface

Directory of Open Access Journals (Sweden)

Gavin Walker

2012-10-01

Full Text Available In this study three chemical agents Amino-propyl-triethoxy-silane (APS, sorbitol ended PLA oligomer (SPLA and Hexamethylene diisocyanate (HDI were identified to be used as coupling agents to react with the phosphate glass fibre (PGF reinforcement and the polylactic acid (PLA polymer matrix of the composite. Composites were prepared with short chopped strand fibres (l = 20 mm, ϕ = 20 µm in a random arrangement within PLA matrix. Improved, initial composite flexural strength (~20 MPa was observed for APS treated fibres, which was suggested to be due to enhanced bonding between the fibres and polymer matrix. Both APS and HDI treated fibres were suggested to be covalently linked with the PLA matrix. The hydrophobicity induced by these coupling agents (HDI, APS helped to resist hydrolysis of the interface and thus retained their mechanical properties for an extended period of time as compared to non-treated control. Approximately 70% of initial strength and 65% of initial modulus was retained by HDI treated fibre composites in contrast to the control, where only ~50% of strength and modulus was retained after 28 days of immersion in PBS at 37 °C. All coupling agent treated and control composites demonstrated good cytocompatibility which was comparable to the tissue culture polystyrene (TCP control, supporting the use of these materials as coupling agent’s within medical implant devices.

Fibre-reinforced SiC ceramics: Properties and applications; Faserverstaerkte SiC-Keramik: Eigenschaften und Anwendungen

Energy Technology Data Exchange (ETDEWEB)

Leuchs, M. [MT Aerospace AG, Franz-Josef-Strauss-Str. 5, 86153 Augsburg (Germany)

2006-04-15

Composite ceramics can be produced by different processes resulting in different qualities. A composite ceramic material with C or SiC fibres and a SiC matrix is presented which is produced by chemical vapour infiltration (CVI). The material characteristics are defined by the embedding of the fibres in the matrix. For full utilisation of the strength and elasticity of the fibres, weak coupling between the fibres and matrix is required. The measured cracking resistances are similar to those of metals, e.g. grey cast iron. Applications so far have focused on applications where known materials cannot be used, e.g. because of high temperatures, thermoshock and brittle fracture problems, and wear. Examples are control flaps in aerospace applications are exposed to temperatures above 1600 degree C during re-entry into the earth atmosphere and heavy-duty sliding bearings in industrial pumps where ceramic composite materials have been in use for more than a decade. (orig.) [German] Mit Verbundkeramiken ist eine Werkstoffklasse entstanden, bei denen sich verschiedene Herstellverfahren mit unterschiedlichen Qualitaeten entwickelt haben [1]. Es wird eine Verbundkeramik mit C- bzw. SiC-Fasern und SiC-Matrix vorgestellt, die ueber die Infiltration der Fasern mit dem CVI-Verfahren (Chemical Vapour Infiltration) hergestellt wird [2]. Die Eigenschaften werden bestimmt durch die Qualitaet der Einbettung der Fasern in die Matrix. Nur eine schwache Ankopplung zwischen Fasern und Matrix erlaubt es, Festigkeit und Dehnbarkeit der Fasern auszunutzen. Die gemessenen Risswiderstaende solcher Verbundkeramiken liegen im Bereich von Metallen wie zum Beispiel Grauguss. Anwendungen konzentrieren sich bisher auf Gebiete, in denen die bekannten Werkstoffe nicht eingesetzt werden koennen. Gruende hierfuer sind zum Beispiel zu hohe Temperaturen, Thermoschock- und Sproedbruchverhalten und Verschleiss. Beispiele sind Steuerklappen aus dem Bereich der Raumfahrt, die beim Wiedereintritt in die

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......2 had positive effect only in DSS-induced colitis. The TFF3 monomer was without any effects in both models. Treatment effect was most pronounced in the middle part of the colon, closest to the tip of the catheter. Injected TFF peptides, especially the TFF3 monomer, aggravated the colitis score...... in both colitis models. CONCLUSIONS: Intracolonic administration of TFF3 dimer and TFF2 improves experimentally induced colitis in rats. The TFF3 monomer has no effect. Parenteral administration of TFF peptides aggravates the colitis especially the TFF3 monomer....

Intestinal Anti-inflammatory Effects of Outer Membrane Vesicles from Escherichia coli Nissle 1917 in DSS-Experimental Colitis in Mice

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María-José Fábrega

2017-07-01

Full Text Available Escherichia coli Nissle 1917 (EcN is a probiotic strain with proven efficacy in inducing and maintaining remission of ulcerative colitis. However, the microbial factors that mediate these beneficial effects are not fully known. Gram-negative bacteria release outer membrane vesicles (OMVs as a direct pathway for delivering selected bacterial proteins and active compounds to the host. In fact, vesicles released by gut microbiota are emerging as key players in signaling processes in the intestinal mucosa. In the present study, the dextran sodium sulfate (DSS-induced colitis mouse model was used to investigate the potential of EcN OMVs to ameliorate mucosal injury and inflammation in the gut. The experimental protocol involved pre-treatment with OMVs for 10 days before DSS intake, and a 5-day recovery period. Oral administration of purified EcN OMVs (5 μg/day significantly reduced DSS-induced weight loss and ameliorated clinical symptoms and histological scores. OMVs treatment counteracted altered expression of cytokines and markers of intestinal barrier function. This study shows for the first time that EcN OMVs can mediate the anti-inflammatory and barrier protection effects previously reported for this probiotic in experimental colitis. Remarkably, translation of probiotics to human healthcare requires knowledge of the molecular mechanisms involved in probiotic–host interactions. Thus, OMVs, as a non-replicative bacterial form, could be explored as a new probiotic-derived therapeutic approach, with even lower risk of adverse events than probiotic administration.

Chaperone-mediated autophagy components are upregulated in sporadic inclusion-body myositis muscle fibres.

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Cacciottolo, M; Nogalska, A; D'Agostino, C; Engel, W K; Askanas, V

2013-12-01

Sporadic inclusion-body myositis (s-IBM) is an age-associated degenerative muscle disease. Characteristic features are muscle-fibre vacuolization and intramuscle-fibre accumulations of multiprotein aggregates, which may result from the demonstrated impairments of the 26S proteasome and autophagy. Chaperone-mediated autophagy (CMA) is a selective form of lysosomal degradation targeting proteins carrying the KFERQ motif. Lysosome-associated membrane protein type 2A (LAMP2A) and the heat-shock cognate protein 70 (Hsc70) constitute specific CMA components. Neither CMA components nor CMA activity has been studied in normal or disease human muscle, to our knowledge. We studied CMA components by immunocytochemistry, immunoblots, real-time PCR and immunoprecipitation in: (a) 16 s-IBM, nine aged-matched normal and nine disease control muscle biopsies; and (b) cultured human muscle fibres (CHMFs) with experimentally inhibited activities of either the 26S proteasome or autophagy. Compared with age-matched controls, in s-IBM muscle, LAMP2A and Hsc70 were on a given transverse section accumulated as aggregates in approximately 5% of muscle fibres, where they (a) colocalized with each other and α-synuclein (α-syn), a CMA-targeted protein; and (b) were bound to each other and to α-syn by immunoprecipitation. By immunoblots, LAMP2A was increased sevenfold P pathogenic aspect in s-IBM. © 2013 British Neuropathological Society.

Timing is critical for effective glucocorticoid receptor mediated repression of the cAMP-induced CRH gene.

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Siem van der Laan

Full Text Available Glucocorticoid negative feedback of the hypothalamus-pituitary-adrenal axis is mediated in part by direct repression of gene transcription in glucocorticoid receptor (GR expressing cells. We have investigated the cross talk between the two main signaling pathways involved in activation and repression of corticotrophin releasing hormone (CRH mRNA expression: cyclic AMP (cAMP and GR. We report that in the At-T20 cell-line the glucocorticoid-mediated repression of the cAMP-induced human CRH proximal promoter activity depends on the relative timing of activation of both signaling pathways. Activation of the GR prior to or in conjunction with cAMP signaling results in an effective repression of the cAMP-induced transcription of the CRH gene. In contrast, activation of the GR 10 minutes after onset of cAMP treatment, results in a significant loss of GR-mediated repression. In addition, translocation of ligand-activated GR to the nucleus was found as early as 10 minutes after glucocorticoid treatment. Interestingly, while both signaling cascades counteract each other on the CRH proximal promoter, they synergize on a synthetic promoter containing 'positive' response elements. Since the order of activation of both signaling pathways may vary considerably in vivo, we conclude that a critical time-window exists for effective repression of the CRH gene by glucocorticoids.

Topical Rosiglitazone Treatment Improves Ulcerative Colitis by Restoring Peroxisome Proliferator-Activated Receptor-gamma Activity

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Pedersen, G.; Brynskov, Jørn

2010-01-01

and functional activity in human colonic epithelium and explored the potential of topical treatment with rosiglitazone (a PPAR gamma ligand) in patients with ulcerative colitis. METHODS: Spontaneous and rosiglitazone-mediated PPAR gamma and adipophillin expression (a gene transcriptionally activated by PPAR...... for 14 days. RESULTS: PPAR gamma expression was fourfold reduced in epithelial cells from inflamed compared with uninflamed mucosa and controls. Adipophillin levels were decreased in parallel. Rosiglitazone induced a concentration-dependent increase in adipophillin levels and restored PPAR gamma activity...... in epithelial cells from inflamed mucosa in vitro. Rosiglitazone enema treatment was well tolerated and reduced the Mayo ulcerative colitis score from 8.9 to 4.3 (P levels in the epithelial cells of the patients, indicating PPAR...

Propolis from Different Geographic Origins Suppress Intestinal Inflammation in a Model of DSS-Induced Colitis is Associated with Decreased Bacteroides spp. in the Gut.

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Wang, Kai; Jin, Xiaolu; Li, Qiangqiang; Sawaya, Alexandra Christine Helena Frankland; Leu, Richard K Le; Conlon, Michael A; Wu, Liming; Hu, Fuliang

2018-06-11

Dietary supplementation with polyphenol-rich propolis can protect against experimentally-induced colitis. We examined whether different polyphenol compositions of Chinese propolis (CP) and Brazilian propolis (BP) influences their ability to protect against dextran sulfate sodium (DSS)-induced colitis in rats. HPLC-DAD/Q-TOF-MS analysis confirmed that polyphenol compositions of CP and BP were dissimilar. Rats were given CP or BP by gavage (300 mg/kg body weight) throughout the study, starting 1 week prior to DSS treatment for 1 week followed by 3 d without DSS. CP and BP significantly reduced the colitis disease activity index relative to controls not receiving propolis, prevented significant DSS-induced colonic tissue damage and increased resistance to DSS-induced colonic oxidative stress as shown by reduced malonaldehyde levels and increased T-AOC levels. CP and BP significantly reduced DSS-induced colonic apoptosis. Colonic inflammatory markers IL-1β, IL-6 and MCP-1 were suppressed by CP and BP, whereas only BP induced expression of TGF-β. CP, not BP, increased the diversity and richness of gut microbiota populations. Both forms of propolis significantly reduced populations of Bacteroides spp. Despite the dissimilar polyphenol compositions of CP and BP, their ability to protect against DSS-induced colitis is similar. Nevertheless, some different physiological impacts were observed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Hepatitis C virus infection induces apoptosis through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway.

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Deng, Lin; Adachi, Tetsuya; Kitayama, Kikumi; Bungyoku, Yasuaki; Kitazawa, Sohei; Ishido, Satoshi; Shoji, Ikuo; Hotta, Hak

2008-11-01

We previously reported that cells harboring the hepatitis C virus (HCV) RNA replicon as well as those expressing HCV NS3/4A exhibited increased sensitivity to suboptimal doses of apoptotic stimuli to undergo mitochondrion-mediated apoptosis (Y. Nomura-Takigawa, et al., J. Gen. Virol. 87:1935-1945, 2006). Little is known, however, about whether or not HCV infection induces apoptosis of the virus-infected cells. In this study, by using the chimeric J6/JFH1 strain of HCV genotype 2a, we demonstrated that HCV infection induced cell death in Huh7.5 cells. The cell death was associated with activation of caspase 3, nuclear translocation of activated caspase 3, and cleavage of DNA repair enzyme poly(ADP-ribose) polymerase, which is known to be an important substrate for activated caspase 3. These results suggest that HCV-induced cell death is, in fact, apoptosis. Moreover, HCV infection activated Bax, a proapoptotic member of the Bcl-2 family, as revealed by its conformational change and its increased accumulation on mitochondrial membranes. Concomitantly, HCV infection induced disruption of mitochondrial transmembrane potential, followed by mitochondrial swelling and release of cytochrome c from mitochondria. HCV infection also caused oxidative stress via increased production of mitochondrial superoxide. On the other hand, HCV infection did not mediate increased expression of glucose-regulated protein 78 (GRP78) or GRP94, which are known as endoplasmic reticulum (ER) stress-induced proteins; this result suggests that ER stress is not primarily involved in HCV-induced apoptosis in our experimental system. Taken together, our present results suggest that HCV infection induces apoptosis of the host cell through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway(s).

Vinpocetine Ameliorates Acetic Acid-Induced Colitis by Inhibiting NF-κB Activation in Mice.

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Colombo, Bárbara B; Fattori, Victor; Guazelli, Carla F S; Zaninelli, Tiago H; Carvalho, Thacyana T; Ferraz, Camila R; Bussmann, Allan J C; Ruiz-Miyazawa, Kenji W; Baracat, Marcela M; Casagrande, Rúbia; Verri, Waldiceu A

2018-04-10

The idiopathic inflammatory bowel diseases (IBD) comprise two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. Recruited neutrophils and macrophages contribute to intestinal tissue damage via production of ROS and NF-κB-dependent pro-inflammatory cytokines. The introduction of anti-TNF-α therapies in the treatment of IBD patients was a seminal advance. This therapy is often limited by a loss of efficacy due to the development of adaptive immune response, underscoring the need for novel therapies targeting similar pathways. Vinpocetine is a nootropic drug and in addition to its antioxidant effect, it is known to have anti-inflammatory and analgesic properties, partly by inhibition of NF-κB and downstream cytokines. Therefore, the present study evaluated the effect of the vinpocetine in a model of acid acetic-induced colitis in mice. Treatment with vinpocetine reduced edema, MPO activity, microscopic score and macroscopic damage, and visceral mechanical hyperalgesia. Vinpocetine prevented the reduction of colonic levels of GSH, ABTS radical scavenging ability, and normalized levels of anti-inflammatory cytokine IL-10. Moreover, vinpocetine reduced NF-κB activation and thereby NF-κB-dependent pro-inflammatory cytokines IL-1β, TNF-α, and IL-33 in the colon. Thus, we demonstrate for the first time that vinpocetine has anti-inflammatory, antioxidant, and analgesic effects in a model of acid acetic-induced colitis in mice and deserves further screening to address its suitability as an approach for the treatment of IBD.

Lactobacillus bulgaricus OLL1181 activates the aryl hydrocarbon receptor pathway and inhibits colitis

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Takamura, Takeyuki; Harama, Daisuke; Fukumoto, Suguru; Nakamura, Yuki; Shimokawa, Naomi; Ishimaru, Kayoko; Ikegami, Shuji; Makino, Seiya; Kitamura, Masanori; Nakao, Atsuhito

2011-01-01

Increasing evidence suggests that the aryl hydrocarbon receptor (AhR) pathway has an important role in the regulation of inflammatory responses. Most recently, we have shown that the activation of the AhR pathway by a potent AhR agonist inhibits the development of dextran sodium sulfate (DSS)-induced colitis, a model of human ulcerative colitis, by the induction of prostaglandin E2 (PGE2) in the large intestine. Because several strains of probiotic lactic acid bacteria have been reported to inhibit DSS-induced colitis by unidentified mechanisms, we hypothesized that particular strains of lactic acid bacterium might have the potential to activate the AhR pathway, thereby inhibiting DSS-induced colitis. This study investigated whether there are specific lactic acid bacterial strains that can activate the AhR pathway, and if so, whether this AhR-activating potential is associated with suppression of DSS-induced colitis. By using AhR signaling reporter cells, we found that Lactobacillus bulgaricus OLL1181 had the potential to activate the AhR pathway. OLL1181 also induced the mRNA expression of cytochrome P450 family 1A1 (CYP1A1), a target gene of the AhR pathway, in human colon cells, which was inhibited by the addition of an AhR antagonist, α-naphthoflavon (αNF). In addition, mice treated orally with OLL1181 showed an increase in CYP1A1 mRNA expression in the large intestine and amelioration of DSS-induced colitis. Thus, OLL1181 can induce activation of the intestinal AhR pathway and inhibit DSS-induced colitis in mice. This strain of lactic acid bacterium has therefore the potential to activate the AhR pathway, which may be able to suppress colitis. PMID:21321579

Reactive arthritis induced by recurrent Clostridium difficile colitis

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Allison Marr

2012-01-01

Full Text Available Clostridium difficile colitis is a common infection that can be difficult to resolve and may result in recurrent infections. Reactive arthritis is a rare presentation of this disease and its treatment is not well differentiated in the literature. We describe a case of reactive arthritis occurring in a patient with a history of recurrent Clostridium difficile colitis while currently receiving a taper of oral vancomycin. His arthritis symptoms resolved with corticosteroids and continued treatment with anticlostridial antibiotics.

SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity.

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Lee, Soonduck; Kim, Jinsun; Jung, Samil; Li, Chengping; Yang, Young; Kim, Keun Il; Lim, Jong-Seok; Kim, Yonghwan; Cheon, Choong-Il; Lee, Myeong-Sok

2015-03-01

Vitamin C is considered as an important anticancer therapeutic agent although this view is debatable. In this study, we introduce a physiological mechanism demonstrating how vitamin C exerts anticancer activity that induces cell cycle arrest and apoptosis. Our previous and current data reveal that p53 tumor suppressor is the prerequisite factor for stronger anticancer effects of vitamin C. In addition, vitamin C-mediated cancer cell cytotoxicity appears to be achieved at least partly through the downregulation of the p34SEI-1 oncoprotein. Our previous study showed that p34SEI-1 increases the survival of various types of cancer cells by inhibiting their apoptosis. Present data suggest that vitamin C treatment decreases the p34SEI-1 expression at the protein level and therefore alleviates its anti-apoptotic activity. Of note, SIAH1, E3 ubiquitin ligase, appears to be responsible for the p34SEI-1 polyubiquitination and its subsequent degradation, which is dependent on p53. In summary, vitamin C increases cancer cell death by inducing SIAH1-mediated polyubiquitination/degradation of the p34SEI-1 oncoprotein in a p53-dependent manner.

Dasatinib-induced hemorrhagic colitis complicated with cytomegalovirus infection

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Aya Nakaya

2017-12-01

Full Text Available A 69-year-old man with chronic-phase chronic myeloid leukemia was initially treated with 100 mg dasatinib once a day. Despite a major molecular response within 9 months, he developed hemorrhagic colitis 32 months after starting dasatinib. Colonoscopy identified multiple hemorrhagic ulcers in the transverse colon. The pathological findings indicated cytomegalovirus infection. Dasatinib was stopped and he was started on ganciclovir. Three months later, colonoscopy confirmed the disappearance of the hemorrhagic ulcers. Dasatinib is a second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia. As a multi-kinase inhibitor that acts on SRC-family kinases, its broader off-target kinase-inhibitory activity may account for the adverse events of dasatinib. Although gastrointestinal bleeding is common in patients taking dasatinib, the combination of cytomegalovirus infection and hemorrhagic colitis in the absence of systemic immunodeficiency is rare. Based on this case of dasatinibinduced hemorrhagic colitis with cytomegalovirus infection, we describe a possible mechanism and effective treatment.

Dihydrotanshinone I, a natural product, ameliorates DSS-induced experimental ulcerative colitis in mice.

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Guo, Yanling; Wu, Xiaxia; Wu, Qin; Lu, Yuanfu; Shi, Jingshan; Chen, Xiuping

2018-04-01

Ulcerative colitis (UC) is a chronic and relapsing inflammatory disorder of the colon and rectum with increasing morbidity in recent years. 15,16-dihydrotanshinone Ӏ (DHT) is a natural product with multiple bioactivities. In this study, we aimed to investigate the protective effect and potential mechanisms of DHT on UC. Dextran sulfate sodium salt (DSS) was administrated in drinking water for 7 days to induce UC in mice. DHT (10 and 25 mg/kg) significantly alleviated DSS-induced body weight loss, disease activity index (DAI) scores, and improved histological alterations of colon tissues. DHT inhibited the myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in colon tissues and decreased serum levels of TNF-α, IL-1β, IL-6, and high-mobility group box 1 (HMGB1). Furthermore, increased expression of kinases receptor-interacting protein 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) and decreased expression of caspase-8 in colon tissues were partially restored by DHT. In LPS-stimulated RAW264.7 macrophages, DHT significantly inhibited generation of nitric oxide, IL-6, TNF-α and protein expression of iNOS, COX-2. In addition, increased expression of iNOS, COX-2, and phosphorylated RIP1, RIP3, MLKL in response to LPS plus Z-VAD (LZ) were also suppressed by DHT. DHT had no effect on TNF-α + BV6 + Z-VAD (TBZ) induced phosphorylation of RIPs and MLKL in HT29 cells. Especially, DHT showed no effect on LZ and TBZ-induced necroptosis in RAW264.7 and HT29 cells, respectively. In summary, DHT alleviated DSS-induced UC in mice by suppressing pro-inflammatory mediators and regulating RIPs-MLKL-caspase-8 axis. Copyright © 2018 Elsevier Inc. All rights reserved.

Bifidobacterium longum CCM 7952 Promotes Epithelial Barrier Function and Prevents Acute DSS-Induced Colitis in Strictly Strain-Specific Manner.

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Dagmar Srutkova

Full Text Available Reduced microbial diversity has been associated with inflammatory bowel disease (IBD and probiotic bacteria have been proposed for its prevention and/or treatment. Nevertheless, comparative studies of strains of the same subspecies for specific health benefits are scarce. Here we compared two Bifidobacterium longum ssp. longum strains for their capacity to prevent experimental colitis.Immunomodulatory properties of nine probiotic bifidobacteria were assessed by stimulation of murine splenocytes. The immune responses to B. longum ssp. longum CCM 7952 (Bl 7952 and CCDM 372 (Bl 372 were further characterized by stimulation of bone marrow-derived dendritic cell, HEK293/TLR2 or HEK293/NOD2 cells. A mouse model of dextran sulphate sodium (DSS-induced colitis was used to compare their beneficial effects in vivo.The nine bifidobacteria exhibited strain-specific abilities to induce cytokine production. Bl 372 induced higher levels of both pro- and anti-inflammatory cytokines in spleen and dendritic cell cultures compared to Bl 7952. Both strains engaged TLR2 and contain ligands for NOD2. In a mouse model of DSS-induced colitis, Bl 7952, but not Bl 372, reduced clinical symptoms and preserved expression of tight junction proteins. Importantly, Bl 7952 improved intestinal barrier function as demonstrated by reduced FITC-dextran levels in serum.We have shown that Bl 7952, but not Bl 372, protected mice from the development of experimental colitis. Our data suggest that although some immunomodulatory properties might be widespread among the genus Bifidobacterium, others may be rare and characteristic only for a specific strain. Therefore, careful selection might be crucial in providing beneficial outcome in clinical trials with probiotics in IBD.

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

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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.

Regulatory role of NKG2D+ NK cells in intestinal lamina propria by secreting double-edged Th1 cytokines in ulcerative colitis.

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Wang, Fan; Peng, Pai-Lan; Lin, Xue; Chang, Ying; Liu, Jing; Zhou, Rui; Nie, Jia-Yan; Dong, Wei-Guo; Zhao, Qiu; Li, Jin

2017-11-17

The role of intestinal lamina propria (LP) NKG2D+ NK cells is unclear in regulating Th1/Th2 balance in ulcerative colitis (UC). In this study, we investigated the frequency of LP NKG2D+ NK cells in DSS-induced colitis model and intestinal mucosal samples of UC patients, as well as the secretion of Th1/Th2/Th17 cytokines in NK cell lines after MICA stimulation. The role of Th1 cytokines in UC was validated by bioinformatics analysis. We found that DSS-induced colitis in mice was characterized by a Th2-mediated process. In acute phrase, the frequency of LP NKG2D+ lymphocytes increased significantly and decreased in remission, while the frequency of LP NKG2D+ NK cells decreased significantly in acute phase and increased in remission. No obvious change was found in the frequency of total LP NK cells. Similarly, severe UC patients had a higher expression of mucosal NKG2D and a lower number of NKG2D+ NK cells than mild to moderate UC. In NK cell lines, the MICA stimulation could induce a predominant secretion of Th1 cytokines (TNF, IFN-γ). Furthermore, in bioinformatics analysis, mucosal Th1 cytokine of TNF, showed a double-edged role in UC when compared to the Th1-mediated disease of Crohn's colitis. In conclusion, LP NKG2D+ NK cells partially played a regulatory role in UC through secreting Th1 cytokines to regulate the Th2-predominant Th1/Th2 imbalance, despite of the concomitant pro-inflammatory effects of Th1 cytokines.

No Protection against DSS-induced Colitis by Short-term Pretreatment with Seal or Fish Oils in Rats

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Gülen Arslan

2007-01-01

Full Text Available Background: Omega-3 (n-3 polyunsaturated fatty acids (PUFAs have modulating effects in several chronic inflammatory conditions. The aim of the present study was to test whether prior short-term dietary supplementation with n-3 (fish or seal oil or n-6 (soy oil PUFA rich oils would protect the development of dextran sulfate sodium (DSS-induced colitis in rats.Methods: Forty-eight male Wistar rats were divided into 6 groups: no intervention, sham, DSS, seal oil + DSS, fi sh oil +DSS and soy oil + DSS. Following 7 days of acclimatisation, 1 mL oil (seal, fish or soy or distilled water (sham was administered by gavage day 8 to 14. Colitis was induced by 5% DSS in drinking water from day 15 to 21. Rats were sacrificed on day 23. Histological colitis (crypt and inflammation scores, faecal granulocyte marker protein (GMP and quantitative fatty acid composition in red blood cells were measured.Results: Pretreatment with fish or seal oils did not significantly influence DSS induced inflammation. In fact, all the oils tended to exacerbate the inflammation. Soy oil increased the mean crypt score (P < 0.04, but not the inflammation score or GMP. The ratio of n-6 to n-3 fatty acids (FAs was 11 to 1 and 10 to 1 in standard diet and in red blood cells of control rats, respectively. Following administration of DSS, the ratio fell in all treatment groups (P < 0.001. The lowest ratios were seen in the groups receiving DSS + fi sh or seal oils (around 6 to 1.Conclusion: Short-term pretreatment with fish or seal oils did not protect against subsequent induction of colitis by DSS in this rat model. Whether the high ratio of n-6 to n-3 FAs in the standard diet concealed effects of n-3 FA supplementation should be further investigated.

Naked gene therapy of hepatocyte growth factor for dextran sulfate sodium-induced colitis in mice

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Kanbe, Takamasa; Murai, Rie; Mukoyama, Tomoyuki; Murawaki, Yoshiyuki; Hashiguchi, Ko-ichi; Yoshida, Yoko; Tsuchiya, Hiroyuki; Kurimasa, Akihiro; Harada, Ken-ichi; Yashima, Kazuo; Nishimuki, Eiji; Shabana, Noriko; Kishimoto, Yukihiro; Kojyo, Haruhiko; Miura, Kunihiko; Murawaki, Yoshikazu; Kawasaki, Hironaka; Shiota, Goshi

2006-01-01

Ulcerative colitis (UC) is progressive and relapsing disease. To explore the therapeutic effects of naked gene therapy of hepatocyte growth factor (HGF) on UC, the SRα promoter driving HGF gene was intrarectally administered to the mice in which colitis was induced by dextran sulfate sodium (DSS). Expression of the transgene was seen in surface epithelium, lamina propria, and muscularis mucosae. The HGF-treated mice showed reduced colonic mucosal damage and increased body weights, compared with control mice (P < 0.01 and P < 0.05, respectively). The HGF-treated mice displayed increased number of PCNA-positive cells and decreased number of apoptotic cells than in control mice (P < 0.01, each). Phosphorylated AKT was dramatically increased after HGF gene administration, however, phosphorylated ERK1/2 was not altered. Microarray analysis revealed that HGF induced expression of proliferation- and apoptosis-associated genes. These data suggest that naked HGF gene delivery causes therapeutic effects through regulation of many downstream genes

Pseudomembranous Colitis: Not Always Caused by Clostridium difficile

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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.

The dual anti-inflammatory and antioxidant activities of natural honey promote cell proliferation and neural regeneration in a rat model of colitis.

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Nooh, Hanaa Z; Nour-Eldien, Nermeen M

2016-07-01

A decreased antioxidant capacity and excessive inflammation are well-known features in the pathogenesis of ulcerative colitis (UC). Recent evidence has suggested a role of honey in reducing colitis-induced inflammatory and oxidative stress markers. In this study, we examined whether the anti-inflammatory and anti-oxidative properties of honey have a beneficial effect on the enteric innervation and cellular proliferation of UC in rat. The colitis was induced in rats by dextran sodium sulphate (DSS). The effect of natural honey on induced colitis was assessed by the following parameters in colonic samples: tissue injury, inflammatory infiltration, interleukin-1β and -6, superoxide dismutase and reduced glutathione. In addition, the expression of tumour necrosis factor-α, inducible NO synthase, caspase-3, CD34, Ki67, S100, c-kit, and neuron-specific enolase were examined by immunohistochemistry. Compared to the DSS-induced colitis group, the honey-treated group had significantly improved macroscopic and microscopic scores and exhibited the down-regulation of oxidative, inflammatory, and apoptotic markers. In addition, up-regulation of intrinsic muscular innervation and epithelial cellular proliferation markers was detected. These results provide new insight into the beneficial role of natural honey in the treatment of DSS-induced colitis via the inhibition of colonic motor dysfunction and the inflammatory-oxidative-apoptotic cascade. In addition, the role of honey in epithelial regeneration was clarified. Copyright © 2016 Elsevier GmbH. All rights reserved.

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.

Dextran sulphate sodium colitis in C57BL/6J mice is alleviated by Lactococcus lactis and worsened by the neutralization of Tumor necrosis Factor α.

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Berlec, Aleš; Perše, Martina; Ravnikar, Matjaž; Lunder, Mojca; Erman, Andreja; Cerar, Anton; Štrukelj, Borut

2017-02-01

TNFα has a well-established role in inflammatory bowel disease that affects the gastrointestinal tract and is usually manifested as Crohn's disease or ulcerative colitis. We have compared Lactococcus lactis NZ9000 displaying TNFα-binding affibody with control Lactococcus lactis and with anti-TNFα antibody infliximab for the treatment of mice with dextran sulphate sodium (DSS)-induced colitis. L. lactis NZ9000 alleviated the colitis severity one week after colitis induction with DSS, more effectively when administered in preventive fashion prior to, during and after DSS administration. TNFα-binding L. lactis was less effective than control L. lactis, particularly when TNFα-binding L. lactis was administered in preventive fashion. Similarly, an apparently detrimental effect of TNFα neutralization was observed in mice that were intraperitoneally administered anti-TNFα monoclonal antibody infliximab prior to colitis induction. The highest concentrations of tissue TNFα were observed in groups without DSS colitis that were treated either with TNFα-binding L. lactis or infliximab. To conclude, we have confirmed that L. lactis exerts a protective effect on DSS-induced colitis in mice. Contrary to expectations, but in line with some reports, the neutralization of TNFα aggravated disease symptoms in the acute phase of colitis and increased TNFα concentration in colon tissue of healthy mice. Nevertheless, we have demonstrated that oral administration of bacteria with surface displayed TNFα-binding affibody can interfere significantly with TNFα signaling and mimic the infliximab response in the given animal model of colitis. Copyright © 2016 Elsevier B.V. All rights reserved.

Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote Interleukin-23 Driven Chronic Colitis

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Griseri, Thibault; Arnold, Isabelle C.; Pearson, Claire; Krausgruber, Thomas; Schiering, Chris; Franchini, Fanny; Schulthess, Julie; McKenzie, Brent S.; Crocker, Paul R.; Powrie, Fiona

2015-01-01

Summary The role of intestinal eosinophils in immune homeostasis is enigmatic and the molecular signals that drive them from protective to tissue damaging are unknown. Most commonly associated with Th2 cell-mediated diseases, we describe a role for eosinophils as crucial effectors of the interleukin-23 (IL-23)-granulocyte macrophage colony-stimulating factor (GM-CSF) axis in colitis. Chronic intestinal inflammation was characterized by increased bone marrow eosinopoiesis and accumulation of activated intestinal eosinophils. IL-5 blockade or eosinophil depletion ameliorated colitis, implicating eosinophils in disease pathogenesis. GM-CSF was a potent activator of eosinophil effector functions and intestinal accumulation, and GM-CSF blockade inhibited chronic colitis. By contrast neutrophil accumulation was GM-CSF independent and dispensable for colitis. In addition to TNF secretion, release of eosinophil peroxidase promoted colitis identifying direct tissue-toxic mechanisms. Thus, eosinophils are key perpetrators of chronic inflammation and tissue damage in IL-23-mediated immune diseases and it suggests the GM-CSF-eosinophil axis as an attractive therapeutic target. PMID:26200014

Immune-related Colitis Induced by the Long-term Use of Nivolumab in a Patient with Non-small Cell Lung Cancer.

Science.gov (United States)

Yasuda, Yuichiro; Urata, Yoshiko; Tohnai, Rie; Ito, Shoichi; Kawa, Yoshitaka; Kono, Yuko; Hattori, Yoshihiro; Tsuda, Masahiro; Sakuma, Toshiko; Negoro, Shunichi; Satouchi, Miyako

2018-05-01

We herein report a case of immune-related colitis induced by the long-term use of nivolumab. A 62-year-old Japanese man was treated with nivolumab at 3 mg/kg every 2 weeks for advanced lung adenocarcinoma. The patient was admitted to our hospital due to non-bloody watery diarrhea after the 70th dose of nivolumab. A biopsy specimen of the colon mucosa revealed evidence of colitis with cryptitis and crypt microabscesses. He was diagnosed with immune-related colitis and started on predonisolone 60 mg/day. Subsequently, his symptoms remarkably resolved. Consideration of immune-related adverse events up to several years after the initiation of nivolumab is important.

Creep properties of discontinuous fibre composites with partly creeping fibres

International Nuclear Information System (INIS)

Bilde-Soerensen, J.B.; Lilholt, H.

1977-05-01

In a previous report (RISO-M-1810) the creep properties of discontinuous fibre composites with non-creeping fibres were analyzed. In the present report this analysis is extended to include the case of discontinuous composites with partly creeping fibres. It is shown that the creep properties of the composite at a given strain rate, epsilonsub(c), depend on the creep properties of the matrix at a strain rate higher than epsilonsub(c), and on the creep properties of the fibres at epsilonsub(c). The composite creep law is presented in a form which permits a graphical determination of the composite creep curve. This can be constructed on the basis of the matrix and the fibre creep curves by vector operations in a log epsilon vs. log sigma diagram. The matrix contribution to the creep strength can be evaluated by a simple method. (author)

Influence of fibre distribution and grain size on the mechanical behaviour of friction stir processed Mg–C composites

Energy Technology Data Exchange (ETDEWEB)

Mertens, A., E-mail: anne.mertens@ulg.ac.be [Université de Liège, Faculty of Applied Science, A& M Department, Metallic Materials Science Unit (Belgium); Simar, A. [Université catholique de Louvain, Institute of Mechanics, Materials and Civil Engineering (Belgium); Adrien, J.; Maire, E. [Institut National des Sciences Appliquées de Lyon (INSA Lyon), MATEIS Laboratory (France); Montrieux, H.-M. [Université de Liège, Faculty of Applied Science, A& M Department, Metallic Materials Science Unit (Belgium); Delannay, F. [Université catholique de Louvain, Institute of Mechanics, Materials and Civil Engineering (Belgium); Lecomte-Beckers, J. [Université de Liège, Faculty of Applied Science, A& M Department, Metallic Materials Science Unit (Belgium)

2015-09-15

Short C fibres–Mg matrix composites have been produced by friction stir processing sandwiches made of a layer of C fabric stacked between two sheets of Mg alloy AZ31B or AZ91D. This novel processing technique can allow the easy production of large-scale metal matrix composites. The paper investigates the microstructure of FSPed C fibre–Mg composites in relation with the fragmentation of the C fibres during FSP and their influence on the tensile properties. 3D X-ray tomography reveals that the fibres orient like onion rings and are more or less fragmented depending on the local shear stress during the process. The fibre volume fraction can be increased from 2.3% to 7.1% by reducing the nugget volume, i.e. by using a higher advancing speed in AZ31B alloy or a stronger matrix alloy, like AZ91D alloy. A higher fibre volume fraction leads to a smaller grain size which brings about an increase of the composite yield strength by 15 to 25%. However, a higher fibre volume fraction also leads to a lower fracture strain. Fracture surface observations reveal that damage occurs by fibre/matrix decohesion along fibres oriented perpendicularly to the loading direction. - Graphical abstract: Display Omitted - Highlights: • C–Mg MMCs were produced by FSP sandwiches made of a C fabric between Mg sheets. • Fibre fragmentation and erosion is larger when the temperature reached during FSP is lower. • A lower advancing speed brings a lower fibre volume fraction and a lower grain size. • X-ray tomography reveals that fibres orient along the FSP material flow. • The fibres and grain size reduction increase the yield strength by 15 to 25%.

Rivastigmine alleviates experimentally induced colitis in mice and rats by acting at central and peripheral sites to modulate immune responses.

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Helena Shifrin

Full Text Available The cholinergic anti-inflammatory system and α7 nicotinic receptors in macrophages have been proposed to play a role in neuroimmunomodulation and in the etiology of ulcerative colitis. We investigated the ability of a cholinesterase (ChE inhibitor rivastigmine, to improve the pathology of ulcerative colitis by increasing the concentration of extracellular acetylcholine in the brain and periphery. In combination with carbachol (10 µM, rivastigmine (1 µM significantly decreased the release of nitric oxide, TNF-α, IL-1β and IL-6 from lipopolysaccharide-activated RAW 264.7 macrophages and this effect was abolished by α7 nicotinic receptor blockade by bungarotoxin. Rivastigmine (1 mg/kg but not (0.5 mg/kg, injected subcutaneously once daily in BALB/c mice with colitis induced by 4% dextran sodium sulphate (DSS, reduced the disease activity index (DAI by 60% and damage to colon structure. Rivastigmine (1 mg/kg also reduced myeloperoxidase activity and IL-6 by >60%, and the infiltration of CD11b expressing cells by 80%. These effects were accompanied by significantly greater ChE inhibition in cortex, brain stem, plasma and colon than that after 0.5 mg/kg. Co-administration of rivastigmine (1 mg/kg with the muscarinic antagonist scopolamine significantly increased the number of CD11b expressing cells in the colon but did not change DAI compared to those treated with rivastigmine alone. Rivastigmine 1 and 2 mg given rectally to rats with colitis induced by rectal administration of 30 mg dintrobezene sulfonic acid (DNBS also caused a dose related reduction in ChE activity in blood and colon, the number of ulcers and area of ulceration, levels of TNF-α and in MPO activity. The study revealed that the ChE inhibitor rivastigmine is able to reduce gastro-intestinal inflammation by actions at various sites at which it preserves ACh. These include ACh released from vagal nerve endings that activates alpha7 nicotinic receptors on circulating macrophages

[Changes of expression of miR-155 in colitis-associated colonic carcinogenesis].

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Li, Weiwei; Han, Wenxiao; Zhao, Xinhua; Wang, Hongying

2014-04-01

To investigate the changes of miR-155 and its target genes in colitis-associated carcinogenesis. Colitis-associated colon cancer was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in C57BL/6 mice. Mice of three different stages during the development of colon cancer were obtained, named AD1, AD2 and AD3, respectively. A control group of mice without any treatment and a DSS only group representing chronic inflammation without cancer were set up as well. Colon tissue was collected and expression of miR-155 in the colon tissues was measured by real-time fluorescent quantitative PCR. TargetScan and PicTar were used to predict potential target genes of miR-155, which were then preliminarily screened with our gene expression microarray database of AOM-DSS mouse model. Regular PCR was used to confirm the changes of the expression of these potential target genes in AOM-DSS mouse model. Colitis-associated colon cancer was effectively induced by azoxymethane and dextran sulfate sodium in C57BL/6 mice. Histological examination revealed that the evolution process was sequentially from normal, mild dysplasia, moderate dysplasia, and severe dysplasia to adenocarcinoma in the AOM-DSS mouse model. The level of miR-155 was gradually elevated with the formation of colitis-associated colon cancer. There was no significant difference between the levels of miR-155 expression in the DSS group (0.005 6 ± 0.003 7) and control group (0.012 0 ± 0.005 1) (P > 0.05), but the level of miR-155 in the AD3 group (0.054 4 ± 0.027 0) was significantly higher than that of the DSS group (0.005 6 ± 0.003 7)(P Bcorl1, Cacna1c, Rspo2 and Foxo3 were potential target genes of miR-155 in the AOM-DSS mouse model. Changes of Kcna1 and Cacna1c in the AOM-DSS mouse model were validated to be consistent with the changes obtained with the gene expression microarray. The up-regulation of miR-155 is related to colitis-associated carcinogenesis, but is irrelevant to chronic inflammation in the

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

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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.

Interleukin 21 controls tumour growth and tumour immunosurveillance in colitis-associated tumorigenesis in mice.

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Jauch, Dominik; Martin, Maria; Schiechl, Gabriela; Kesselring, Rebecca; Schlitt, Hans Jürgen; Geissler, Edward K; Fichtner-Feigl, Stefan

2011-12-01

Colitis-associated tumorigenesis is a balance between proliferation of tumour cells and tumour immunosurveillance. The role of T-helper-cell-derived cytokines in tumour growth is not fully understood. In this study the authors investigated the influence of interleukin (IL) 21 on intestinal tumorigenesis. Chronic colitis was induced in IL-21(-/-) and littermate control wild-type mice with three cycles of 1.5% dextran sulphate sodium (DSS) over 7 days followed by 7 days of drinking water. Mice received an azoxymethane injection on day 0 of DSS-colitis to induce tumorigenesis. Immunohistochemistry was performed on inflamed and tumour-bearing areas of colons. Cytokine expression of isolated colonic CD4 T cells was determined by ELISA. Cytotoxic capacity of isolated colonic CD8 T cells targeting tumour cells was evaluated by flow cytometry and quantitative cytotoxicity assay. Apoptosis of tumour cells was determined by TUNEL assay of colonic sections. Increasing expression of IL-21 was observed in chronic colitis, which showed functional importance, since IL-21 deficiency prevented chronic DSS-colitis development. Further, in the absence of IL-21, significantly fewer tumour nodules were detected, despite a similar extent of intestinal inflammation. In wild-type mice, 8.6±1.9 tumour nodules were found compared with 1.0±1.2 in IL-21-deficient mice. In tumour-bearing IL-21-deficient mice, intestinal inflammation was restored and partly dependent on interferon (IFN)-γ, whereas the inflammation in wild-type mice showed high IL-17A concentrations. In these rare tumours in IL-21-deficient mice, tumour cell proliferation (Ki-67) was decreased, while cell apoptosis was increased, compared with wild-type mice. Increased IFNγ expression in tumour-bearing IL-21-deficient mice led to increased tumour immunosurveillance mediated by cytotoxic CD8CD103 T cells targeting E-cadherin(+) colonic tumour cells and therefore limited tumour growth. These results indicate that IL-21

Simultaneous Onset of Ulcerative Colitis and Disseminated Pyoderma Gangrenosum

OpenAIRE

Albrecht Neesse; Patrick Michl; Steffen Kunsch; Volker Ellenrieder; Thomas M. Gress; Martin Steinkamp

2007-01-01

Pyoderma gangrenosum (PG) is an immune-mediated inflammatory skin condition representing one of the most distinct extraintestinal manifestations of inflammatory bowel disease (IBD). PG occurs independently from intestinal disease activity in about 1–2% of patients suffering from ulcerative colitis or Crohn's disease and is characterized by chronic deep skin ulcers whose exact pathogenesis is still unknown. So far, patients with ulcerative colitis have only been reported to develop PG during t...

Foeniculum vulgare essential oil ameliorates acetic acid-induced colitis in rats through the inhibition of NF-kB pathway.

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Rezayat, Seyed Mahdi; Dehpour, Ahmad-Reza; Motamed, Saeed Mohammadi; Yazdanparast, Maryam; Chamanara, Mohsen; Sahebgharani, Mousa; Rashidian, Amir

2017-10-24

The aim of the present study is to investigate the protective effects of Foeniculum vulgare essential oil on intestinal inflammation through the inhibition of NF-kB pathway in acetic acid-induced rat colitis. Acute colitis was induced by intra-rectal administration of 2 mL of diluted acetic acid (4%) solution. Two hours after the induction of colitis, 0.2% tween 80 in normal saline, dexamethasone (2 mg/kg) and F. vulgare essential oil (100, 200, 400 mg/kg) were administered to the animals by oral gavage and continued for 5 consecutive days. Assessment of macroscopic and microscopic lesions was done. MPO activity was evaluated by biochemical method. Furthermore, TNF-α activity was detected by immunohistochemistry (IHC) and the expression level of p-NF-kB p65 protein was measured by western blot analysis. Dexamethasone and F. vulgare essential oil (200, 400 mg/kg) reduced the macroscopic and microscopic lesions compared to the acetic acid group (p kB p65 protein (p kB pathway.

Lactulose mediates suppression of dextran sodium sulfate-induced colon inflammation by increasing hydrogen production.

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Chen, Xiao; Zhai, Xiao; Shi, Jiazi; Liu, Wen Wu; Tao, Hengyi; Sun, Xuejun; Kang, Zhimin

2013-06-01

Molecular hydrogen (H2) is a potent antioxidant and able to protect organs from oxidative stress injuries. Orally administered lactulose, a potent H2 inducer, is digested by colon microflora and significantly increases H2 production, indicating its potential anti-inflammatory action. To evaluate the anti-inflammatory effects of lactulose on dextran sodium sulfate (DSS)-induced colitis in mice. Mice were randomly assigned into seven groups, receiving regular distilled water, H2-rich saline (peritoneal injection), DSS, oral lactulose (0.1, 0.15, 0.2 ml/10 g, respectively), and lactulose (0.2 ml/10 g) + oral antibiotics. The mouse model of human ulcerative colitis was established by supplying mice with water containing DSS. The H2 breath test was used to determine the exhaled H2 concentration. Body weight, colitis score, colon length, pathological features and tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), maleic dialdehyde (MDA) and marrow peroxidase (MPO) levels in colon lesions were evaluated. After 7 days, DSS-induced loss of body weight, increase of colitis score, shortening of colon length, pathological changes and elevated levels of TNF-α, IL-1β, MDA, and MPO in colon lesions, were significantly suppressed by oral lactulose administration and intraperitoneally injected H2-rich saline. Ingestion of antibiotics significantly compromised the anti-inflammatory effects of lactulose. The H2 breath test showed that lactulose administration significantly induced hydrogen production and that antibiotics administration could inhibit H2 production. Lactulose can prevent the development of DSS-induced colitis and alleviate oxidative stress in the colon, as measured by MDA and MPO, probably by increasing endogenous H2 production.

In vivo assessment of 111In labelled lymphocyte gut homing in a TNBS colitis mouse model determined by dedicated animal pinhole SPECT

International Nuclear Information System (INIS)

Bennink, R.J.; Bruin, C.M. de; Montfrans, C. van; Jonge, W.J. de; Deventer, S.J. van; Velde, A.A. te

2002-01-01

Aims: The increasing knowledge of the molecular basis of leukocyte trafficking results in the development of novel anti-inflammatory strategies for inflammatory bowel disease (IBD). For optimal evaluation of therapy efficacy, information about inflammatory activity in bowel segments or lymphocyte recirculation and kinetics in the follow-up of experimental treatment for IBD is needed. The aim of this study was to evaluate a non-invasive scintigraphic technique, able to assess lymphocyte trafficking in a trinitrobenzene sulfonic acid (TNBS) induced mouse colitis model of IBD. Materials and Methods: TNBS sensitised and non-sensitised murine total splenocytes, isolated from donor TNBS colitis or placebo treated BALB/c mice, were labelled in vitro with 111 In-oxine and injected intravenously into recipient BALB/c mice with TNBS-induced colitis or healthy BALB/c mice instilled with saline. Biodistribution and specific radioactive uptake, representing transferred cells, was determined by serial dedicated animal planar scintigraphy and pinhole SPECT of the abdomen 4, 24 and 48h post injection of labelled cells. Moreover, the severity of inflammation in recipient mice was determined by histological scoring. Results: Lymphocyte migration to the inflamed colon of recipient mice increased in time and was maximal at 48h after administration of the 111 In-oxine labelled donor splenocytes. The highest specific radioactive uptake ratio in the colon after 48h was observed in recipient mice with TNBS colitis that received TNBS sensitised lymphocytes (saline vs. TNBS colitis resp. 0.22 ± 0.035 and 0.51 ± 0.033 mean ± SEM p<0.01). Histological scoring confirmed colitis in the TNBS colitis recipient groups and excluded colitis in the saline instilled recipient groups. TNBS colitis recipient mice that received sensitised lymphocytes had a more severe colitis upon histological evaluation as compared with TNBS colitis recipient mice receiving non-sensitised cells (mean histological

Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis.

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Song, Yu-Feng; Hogstrand, Christer; Wei, Chuan-Chuan; Wu, Kun; Pan, Ya-Xiong; Luo, Zhi

2017-09-01

The present study was performed to determine the effect of Zn exposure influencing endoplasmic reticulum (ER) stress, explore the underlying molecular mechanism of Zn-induced hepatic lipolysis in a fish species of significance for aquaculture, yellow catfish Pelteobagrus fulvidraco. We found that waterborne Zn exposure evoked ER stress and unfolded protein response (UPR), and activated cAMP/PKA pathway, and up-regulated hepatic lipolysis. The increase in ER stress and lipolysis were associated with activation of cAMP/PKA signaling pathway. Zn also induced an increase in intracellular Ca 2+ level, which could be partially prevented by dantrolene (RyR receptor inhibitor) and 2-APB (IP3 receptor inhibitor), demonstrating that the disturbed Ca 2+ homeostasis in ER contributed to ER stress and dysregulation of lipolysis. Inhibition of ER stress by PBA attenuated UPR, inhibited the activation of cAMP/PKA pathway and resulted in down-regulation of lipolysis. Inhibition of protein kinase RNA-activated-like ER kinase (PERK) by GSK2656157 and inositol-requiring enzyme (IRE) by STF-083010 differentially influenced Zn-induced changes of lipid metabolism, indicating that PERK and IRE pathways played different regulatory roles in Zn-induced lipolysis. Inhibition of PKA by H89 blocked the Zn-induced activation of cAMP/PKA pathway with a concomitant inhibition of ER stress-mediated lipolysis. Taken together, our findings highlight the importance of the ER stress-cAMP/PKA axis in Zn-induced lipolysis, which provides new insights into Zn toxicology in fish and probably in other vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells.

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Masashi Ohno

Full Text Available Curcumin is a hydrophobic polyphenol derived from turmeric, a traditional Indian spice. Curcumin exhibits various biological functions, but its clinical application is limited due to its poor absorbability after oral administration. A newly developed nanoparticle curcumin shows improved absorbability in vivo. In this study, we examined the effects of nanoparticle curcumin (named Theracurmin on experimental colitis in mice.BALB/c mice were fed with 3% dextran sulfate sodium (DSS in water. Mucosal cytokine expression and lymphocyte subpopulation were analyzed by real-time PCR and flow cytometry, respectively. The profile of the gut microbiota was analyzed by real-time PCR.Treatment with nanoparticle curcumin significantly attenuated body weight loss, disease activity index, histological colitis score and significantly improved mucosal permeability. Immunoblot analysis showed that NF-κB activation in colonic epithelial cells was significantly suppressed by treatment with nanoparticle curcumin. Mucosal mRNA expression of inflammatory mediators was significantly suppressed by treatment with nanoparticle curcumin. Treatment with nanoparticle curcumin increased the abundance of butyrate-producing bacteria and fecal butyrate level. This was accompanied by increased expansion of CD4+ Foxp3+ regulatory T cells and CD103+ CD8α- regulatory dendritic cells in the colonic mucosa.Treatment with nanoparticle curcumin suppressed the development of DSS-induced colitis potentially via modulation of gut microbial structure. These responses were associated with induction of mucosal immune cells with regulatory properties. Nanoparticle curcumin is one of the promising candidates as a therapeutic option for the treatment of IBD.

Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-a and interleukin-18 in BALB/c and severe combined immunodeficiency mice

NARCIS (Netherlands)

Hudcovic, T.; Kolinska, J.; Klepetar, J.; Stepankova, R.; Rezanka, T.; Srutkova, D.; Schwarzer, M.; Erban, V.; Du, Z.; Wells, J.; Hrncir, T.; Tlaskalova-Hogenova, H.; Kozakova, H.

2012-01-01

One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced

Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome

Science.gov (United States)

Ruiz, Pedro A; Morón, Belen; Becker, Helen M; Lang, Silvia; Atrott, Kirstin; Spalinger, Marianne R; Scharl, Michael; Wojtal, Kacper A; Fischbeck-Terhalle, Anne; Frey-Wagner, Isabelle; Hausmann, Martin; Kraemer, Thomas; Rogler, Gerhard

2017-01-01

Objective Western lifestyle and diet are major environmental factors playing a role in the development of IBD. Titanium dioxide (TiO2) nanoparticles are widely used as food additives or in pharmaceutical formulations and are consumed by millions of people on a daily basis. We investigated the effects of TiO2 in the development of colitis and the role of the nucleotide-binding oligomerisation domain receptor, pyrin domain containing (NLRP)3 inflammasome. Design Wild-type and NLRP3-deficient mice with dextran sodium sulfate-induced colitis were orally administered with TiO2 nanoparticles. The proinflammatory effects of TiO2 particles in cultured human intestinal epithelial cells (IECs) and macrophages were also studied, as well as the ability of TiO2 crystals to traverse IEC monolayers and accumulate in the blood of patients with IBD using inductively coupled plasma mass spectrometry. Results Oral administration of TiO2 nanoparticles worsened acute colitis through a mechanism involving the NLRP3 inflammasome. Importantly, crystals were found to accumulate in spleen of TiO2-administered mice. In vitro, TiO2 particles were taken up by IECs and macrophages and triggered NLRP3-ASC-caspase-1 assembly, caspase-1 cleavage and the release of NLRP3-associated interleukin (IL)-1β and IL-18. TiO2 also induced reactive oxygen species generation and increased epithelial permeability in IEC monolayers. Increased levels of titanium were found in blood of patients with UC having active disease. Conclusion These findings indicate that individuals with a defective intestinal barrier function and pre-existing inflammatory condition, such as IBD, might be negatively impacted by the use of TiO2 nanoparticles. PMID:26848183

Effect of live Salmonella Ty21a in Dextran Sulfate Sodium-induced Colitis

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Gunnar Nysœter

2007-01-01

Full Text Available Background Intestinal microbiota seems to play an essential role in the development of inflammatory bowel diseases (IBD. We hypothesised that an oral vaccine based on live Salmonella typhi would be well tolerated and could even attenuate dextran sulfate sodium (DSS induced colitis in rats, an animal model of IBD. Methods Nine male Wistar rats was used for an initial tolerance study, in which we used 3 dose-levels of Salmonella Ty21a, 0.5 × 10 9 , 1 × 10 9 , and 2 × 10 9 CFU, each dose being tested in 3 rats. Four treatment groups consisting of 8 male Wistar rats per group: 1 control group given standard food and water, 2 control group given four daily administrations of Salmonella Ty21a 1 × 10 9 CFU, 3 water with 5% DSS the last 7 days, 4 four daily administrations of Salmonella Ty21a before water with 5% DSS the last 7 days. The Salmonella Ty21a was administered by gastric gavage on day 1, 3, 5 and 16, while DSS was given with the drinking water from day 15 to 22. The animals were sacrificed and colonic tissue removed for analysis 22 days after gavage of the first vaccine dose. Results The animals in the tolerance study got no signs of disease. In the treatment study, all animals receiving DSS had histologic indications of colitis, particularly in the distal part of the colon. Administration of Salmonella Ty21a had no significant effect on crypt and inflammation scores (p > 0.05. Conclusion Gastric administration of live vaccine strain Salmonella Ty21a was well tolerated, but did not provide any significant protection against development of DSS induced colitis in rats.

Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome.

Science.gov (United States)

Ruiz, Pedro A; Morón, Belen; Becker, Helen M; Lang, Silvia; Atrott, Kirstin; Spalinger, Marianne R; Scharl, Michael; Wojtal, Kacper A; Fischbeck-Terhalle, Anne; Frey-Wagner, Isabelle; Hausmann, Martin; Kraemer, Thomas; Rogler, Gerhard

2017-07-01

Western lifestyle and diet are major environmental factors playing a role in the development of IBD. Titanium dioxide (TiO 2 ) nanoparticles are widely used as food additives or in pharmaceutical formulations and are consumed by millions of people on a daily basis. We investigated the effects of TiO 2 in the development of colitis and the role of the nucleotide-binding oligomerisation domain receptor, pyrin domain containing (NLRP)3 inflammasome. Wild-type and NLRP3-deficient mice with dextran sodium sulfate-induced colitis were orally administered with TiO 2 nanoparticles. The proinflammatory effects of TiO 2 particles in cultured human intestinal epithelial cells (IECs) and macrophages were also studied, as well as the ability of TiO 2 crystals to traverse IEC monolayers and accumulate in the blood of patients with IBD using inductively coupled plasma mass spectrometry. Oral administration of TiO 2 nanoparticles worsened acute colitis through a mechanism involving the NLRP3 inflammasome. Importantly, crystals were found to accumulate in spleen of TiO 2 -administered mice. In vitro, TiO 2 particles were taken up by IECs and macrophages and triggered NLRP3-ASC-caspase-1 assembly, caspase-1 cleavage and the release of NLRP3-associated interleukin (IL)-1β and IL-18. TiO 2 also induced reactive oxygen species generation and increased epithelial permeability in IEC monolayers. Increased levels of titanium were found in blood of patients with UC having active disease. These findings indicate that individuals with a defective intestinal barrier function and pre-existing inflammatory condition, such as IBD, might be negatively impacted by the use of TiO 2 nanoparticles. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Dietary α-mangostin, a xanthone from mangosteen fruit, exacerbates experimental colitis and promotes dysbiosis in mice.

Science.gov (United States)

Gutierrez-Orozco, Fabiola; Thomas-Ahner, Jennifer M; Berman-Booty, Lisa D; Galley, Jeffrey D; Chitchumroonchokchai, Chureeporn; Mace, Thomas; Suksamrarn, Sunit; Bailey, Michael T; Clinton, Steven K; Lesinski, Gregory B; Failla, Mark L

2014-06-01

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. α-Mangostin (α-MG), the most abundant xanthone in mangosteen fruit, exerts anti-inflammatory and antibacterial activities in vitro. We evaluated the impact of dietary α-MG on murine experimental colitis and on the gut microbiota of healthy mice. Colitis was induced in C57BL/6J mice by administration of dextran sulfate sodium (DSS). Mice were fed control diet or diet with α-MG (0.1%). α-MG exacerbated the pathology of DSS-induced colitis. Mice fed diet with α-MG had greater colonic inflammation and injury, as well as greater infiltration of CD3(+) and F4/80(+) cells, and colonic myeloperoxidase, than controls. Serum levels of granulocyte colony-stimulating factor, IL-6, and serum amyloid A were also greater in α-MG-fed animals than in controls. The colonic and cecal microbiota of healthy mice fed α-MG but no DSS shifted to an increased abundance of Proteobacteria and decreased abundance of Firmicutes and Bacteroidetes, a profile similar to that found in human UC. α-MG exacerbated colonic pathology during DSS-induced colitis. These effects may be associated with an induction of intestinal dysbiosis by α-MG. Our results suggest that the use of α-MG-containing supplements by patients with UC may have unintentional risk. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of Arctium lappa L. in the dextran sulfate sodium colitis mouse model.

Science.gov (United States)

Huang, Tzou-Chi; Tsai, Shinn-Shyong; Liu, Li-Fang; Liu, Yu Lin; Liu, Hung-Jen; Chuang, Kuo Pin

2010-09-07

To analyze the possible protective role of Arctium lappa L. (AL) in a murine model of ulcerative colitis (UC). BALB/c mice were administered 100 mg/kg AL powder orally each day. After 7 d, colitis was induced by administration of dextran sulfate sodium (DSS) (5% W/V) in drinking water for a further 8 consecutive days. Diarrhea and bloody stools as well as colonic histology were observed. The level of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in colonic sections were detected by immunohistochemistry. There were significant differences in mean body weight values and disease activity indices between controls and AL-treated animals. Moreover, the histological findings showed that AL treatment can prevent mucosal edema, submucosal erosions, ulceration, inflammatory cell infiltration and colon damage. In addition, immunohistochemistry analysis showed that the levels of the inflammatory cytokines, IL-6 and TNF-alpha were also decreased in AL-treated groups. We suggest that AL can prevent intestinal damage and decrease inflammatory cytokines in mice with DSS-induced colitis. Thus, AL could prove to be a useful food for UC.

Effect of Azadirachta indica leaves extract on acetic acid-induced colitis in rats:Role of antioxidants, free radicals and myeloperoxidase

Directory of Open Access Journals (Sweden)

Ghatule RR

2012-10-01

Full Text Available Objective: To evaluate the healing effects of extract of dried leaves of Azadirachta indica (Neem on acetic acid-induced colitis in rats. Neem tree is known as ‘arishtha ’ in Sanskrit, meaning ‘reliever of sicknesses ’. Methods: 50% ethanolic extract of Azadirachta indica leaves was administered orally, once daily for 14 days in rats after the induction of colitis with acetic acid and 500 mg/kg dose of extract was found to have an optimal effect against acetic acid-induced colonic damage score, weight and adhesions (Macroscopic. Effect of Azadirachta indica extract was then further studied on various physical (mucous/blood in stool, food and water intake and body weight changes, colonic mucosal damage and inflammation (microscopic, antibacterial and biochemical parameters viz. i antioxidants (superoxide dismutase, catalase and reduced glutathione and ii free radicals (nitric oxide and lipid peroxidation and myeloperoxidase (acute inflammatory marker activities in acetic acid-induced colitis. Results: Azadirachta indica extract decreased colonic mucosal damage and inflammation (macroscopic and microscopic, mucous/bloody diarrhea, fecal frequency and increased body weight. Azadirachta indica extract showed intestinal antibacterial activity and enhanced the antioxidants but decreased free radicals and myeloperoxidase activities. Acute toxicity study indicated no mortality or other ANS or CNS related adverse effects even with 5.0 g/kg dose (10 times of effective dose indicating its safety. Conclusions: Azadirachta indica seemed to be safe and effective in colitis by its predominant effect on promoting antioxidant status and decreasing intestinal bacterial load, free radicals and myeloperoxidase responsible for tissue damage and delayed healing.

Development of high temperature resistant ceramic matrix composites based on SiC- and novel SiBNC-fibres

International Nuclear Information System (INIS)

Daenicke, Enrico

2014-01-01

Novel ceramic fibres in the quaternary system Si-B-C-N exhibit excellent high temperature stability and creep resistance. In th is work it was investigated, to what extent these outstanding properties of SiBNC-fibres can be transferred into ceramic matrix composites (CMC) in comparison to commercial silicon carbide (SiC) fibres. For the CMC development the liquid silicon infiltration (LSI) as well as the polymer infiltration and pyrolysis process (PIP) was applied. Extensive correlations between fibre properties, fibre coating (without, pyrolytic carbon, lanthanum phosphate), process parameters of the CMC manufacturing method and the mechanical and microstructural properties of the CMC before and after exposure to air could be established. Hence, the potential of novel CMCs can be assessed and application fields can be derived.

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

the effect of TFF3 on dextrane sulfate sodium (DSS)-induced colitis in mice. Expression of endogenous TFF1-3 was examined by in situ hybridization and immunohistochemistry, and the distribution of intravenously, intraperitoneally, and subcutaneously administered (125)I-TFF3 by autoradiography and gamma......-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...

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

Directory of Open Access Journals (Sweden)

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.

Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis.

Science.gov (United States)

Lagishetty, Venu; Misharin, Alexander V; Liu, Nancy Q; Lisse, Thomas S; Chun, Rene F; Ouyang, Yi; McLachlan, Sandra M; Adams, John S; Hewison, Martin

2010-06-01

Vitamin D insufficiency is a global health issue. Although classically associated with rickets, low vitamin D levels have also been linked to aberrant immune function and associated health problems such as inflammatory bowel disease (IBD). To test the hypothesis that impaired vitamin D status predisposes to IBD, 8-wk-old C57BL/6 mice were raised from weaning on vitamin D-deficient or vitamin D-sufficient diets and then treated with dextran sodium sulphate (DSS) to induce colitis. Vitamin D-deficient mice showed decreased serum levels of precursor 25-hydroxyvitamin D(3) (2.5 +/- 0.1 vs. 24.4 +/- 1.8 ng/ml) and active 1,25-dihydroxyvitamin D(3) (28.8 +/- 3.1 vs. 45.6 +/- 4.2 pg/ml), greater DSS-induced weight loss (9 vs. 5%), increased colitis (4.71 +/- 0.85 vs. 1.57 +/- 0.18), and splenomegaly relative to mice on vitamin D-sufficient chow. DNA array analysis of colon tissue (n = 4 mice) identified 27 genes consistently (P < 0.05) up-regulated or down-regulated more than 2-fold in vitamin D-deficient vs. vitamin D-sufficient mice, in the absence of DSS-induced colitis. This included angiogenin-4, an antimicrobial protein involved in host containment of enteric bacteria. Immunohistochemistry confirmed that colonic angiogenin-4 protein was significantly decreased in vitamin D-deficient mice even in the absence of colitis. Moreover, the same animals showed elevated levels (50-fold) of bacteria in colonic tissue. These data show for the first time that simple vitamin D deficiency predisposes mice to colitis via dysregulated colonic antimicrobial activity and impaired homeostasis of enteric bacteria. This may be a pivotal mechanism linking vitamin D status with IBD in humans.

A new therapeutic association to manage relapsing experimental colitis: Doxycycline plus Saccharomyces boulardii.

Science.gov (United States)

Garrido-Mesa, José; Algieri, Francesca; Rodriguez-Nogales, Alba; Utrilla, Maria Pilar; Rodriguez-Cabezas, Maria Elena; Zarzuelo, Antonio; Ocete, Maria Angeles; Garrido-Mesa, Natividad; Galvez, Julio

2015-07-01

Immunomodulatory antibiotics have been proposed for the treatment of multifactorial conditions such as inflammatory bowel disease. Probiotics are able to attenuate intestinal inflammation, being considered as safe when chronically administered. The aim of the study was to evaluate the anti-inflammatory effects of doxycycline, a tetracycline with immunomodulatory properties, alone and in association with the probiotic Saccharomyces boulardii CNCMI-745. Doxycycline was assayed both in vitro (Caco-2 epithelial cells and RAW 264.7 macrophages) and in vivo, in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis and the dextran sodium sulfate (DSS) model of mouse colitis. In addition, the anti-inflammatory effect of the association of doxycycline and the probiotic was evaluated in vitro and in vivo in a DSS model of reactivated colitis in mice. Doxycycline displayed immunomodulatory activity in vitro, reducing IL-8 production by intestinal epithelial cells and nitric oxide by macrophages. Doxycycline administration to TNBS-colitic rats (5, 10 and 25 mg/kg) ameliorated the intestinal inflammatory process, being its efficacy comparable to that previously showed by minocycline. Doxycycline treatment was also effective in reducing acute intestinal inflammation in the DSS model of mouse colitis. The association of doxycycline and S. boulardii helped managing colitis in a reactivated model of colitis, by reducing intestinal inflammation and accelerating the recovery and attenuating the relapse. This was evidenced by a reduced disease activity index, colonic tissue damage and expression of inflammatory mediators. This study confirms the intestinal anti-inflammatory activity of doxycycline and supports the potential use of its therapeutic association with S. boulardii for the treatment of inflammatory bowel diseases, in which doxycycline is used to induce remission and long term probiotic administration helps to prevent the relapses. Copyright © 2015 Elsevier Ltd. All

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

Science.gov (United States)

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

2014-06-30

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

Investigations of plasma induced effects on the surface properties of lignocellulosic natural coir fibres

Science.gov (United States)

Praveen, K. M.; Thomas, Sabu; Grohens, Yves; Mozetič, Miran; Junkar, Ita; Primc, Gregor; Gorjanc, Marija

2016-04-01

The development of lignocellulosic natural-fibre-reinforced polymers composites are constrained by two limitations: the upper temperature at which the fibre can be processed and the significant differences between the surface energy of the fibre and the polymer matrix. Since the fibres and matrices are chemically different, strong adhesion at their interface is needed for the effective transfer of stress and bond distribution throughout the interface. The present study investigated the plasma induced effects on the surface properties of natural coir fibres. Weakly ionized oxygen plasma was created in two different discharge chambers by an inductively coupled radiofrequency (RF) discharge. The water absorption studies showed an increase of water sorption from 39% to 100%. The morphological study using scanning electron microscopy (SEM) analysis also confirmed the surface changes which were observed after the plasma treatment. The topographic measurements and phase imaging done using atomic force microscopy (AFM) indicated difference in topographic features and etching of coir wall, which points to the removal of the first layer of coir fibre. X-ray photoelectron spectroscopy (XPS) analysis revealed that the oxygen content measured for samples treated at 50 Pa increased from initial 18% to about 32%.

A Continuously Tunable Erbium-Doped Fibre Laser Using Tunable Fibre Bragg Gratings and Optical Circulator

International Nuclear Information System (INIS)

Peng, Liu; Feng-Ping, Yan; Jian, Li; Lin, Wang; Ti-Gang, Ning; Tao-Rong, Gong; Shui-Sheng, Jian

2008-01-01

A continuously tunable erbium-doped fibre laser (TEDFL) based on tunable fibre Bragger grating (TFBG) and a three-port optical circulator (OC) is proposed and demonstrated. The OC acts as a 100%-reflective mirror. A strain-induced uniform fibre Bragger grating (FBG) which functions as a partial-reflecting mirror is implemented in the linear cavity. By applying axial strain onto the TFBG, a continuously tunable lasing output can be realized. The wavelength tuning range covers approximately 7.00nm in C band (from 1543.6161 to 1550.3307nm). The side mode suppression ratio (SMSR) is better than 50 dB, and the 3 dB bandwidth of the laser is less than 0.01 nm. Moreover, an array waveguide grating (AWG) is inserted into the cavity for wavelength preselecting, and a 50 km transmission experiment was performed using our TEDFL at a 10Gb/s modulation rate

Submucosal neurons and enteric glial cells expressing the P2X7 receptor in rat experimental colitis.

Science.gov (United States)

da Silva, Marcos Vinícius; Marosti, Aline Rosa; Mendes, Cristina Eusébio; Palombit, Kelly; Castelucci, Patricia

2017-06-01

The aim of this study was to evaluate the effect of ulcerative colitis on the submucosal neurons and glial cells of the submucosal ganglia of rats. 2,4,6-Trinitrobenzene sulfonic acid (TNBS; colitis group) was administered in the colon to induce ulcerative colitis, and distal colons were collected after 24h. The colitis rats were compared with those in the sham and control groups. Double labelling of the P2X7 receptor with calbindin (marker for intrinsic primary afferent neurons, IPANs, submucosal plexus), calretinin (marker for secretory and vasodilator neurons of the submucosal plexus), HuC/D and S100β was performed in the submucosal plexus. The density (neurons per area) of submucosal neurons positive for the P2X7 receptor, calbindin, calretinin and HuC/D decreased by 21%, 34%, 8.2% and 28%, respectively, in the treated group. In addition, the density of enteric glial cells in the submucosal plexus decreased by 33%. The profile areas of calbindin-immunoreactive neurons decreased by 25%. Histological analysis revealed increased lamina propria and decreased collagen in the colitis group. This study demonstrated that ulcerative colitis affected secretory and vasodilatory neurons, IPANs and enteric glia of the submucosal plexus expressing the P2X7 receptor. Copyright © 2017 Elsevier GmbH. All rights reserved.

Interactions Between Diet and the Intestinal Microbiota Alter Intestinal Permeability and Colitis Severity in Mice.

Science.gov (United States)

Llewellyn, Sean R; Britton, Graham J; Contijoch, Eduardo J; Vennaro, Olivia H; Mortha, Arthur; Colombel, Jean-Frederic; Grinspan, Ari; Clemente, Jose C; Merad, Miriam; Faith, Jeremiah J

2018-03-01

It is not clear how the complex interactions between diet and the intestinal microbiota affect development of mucosal inflammation or inflammatory bowel disease. We investigated interactions between dietary ingredients, nutrients, and the microbiota in specific pathogen-free (SPF) and germ-free (GF) mice given more than 40 unique diets; we quantified individual and synergistic effects of dietary macronutrients and the microbiota on intestinal health and development of colitis. C56BL/6J SPF and GF mice were placed on custom diets containing different concentrations and sources of protein, fat, digestible carbohydrates, and indigestible carbohydrates (fiber). After 1 week, SPF and GF mice were given dextran sulfate sodium (DSS) to induce colitis. Disease severity was determined based on the percent weight change from baseline, and modeled as a function of the concentration of each macronutrient in the diet. In unchallenged mice, we measured intestinal permeability by feeding mice labeled dextran and measuring levels in blood. Feces were collected and microbiota were analyzed by 16S rDNA sequencing. We collected colons from mice and performed transcriptome analyses. Fecal microbiota varied with diet; the concentration of protein and fiber had the strongest effect on colitis development. Among 9 fiber sources tested, psyllium, pectin, and cellulose fiber reduced the severity of colitis in SPF mice, whereas methylcellulose increased severity. Increasing dietary protein increased the density of the fecal microbiota and the severity of colitis in SPF mice, but not in GF mice or mice given antibiotics. Psyllium fiber reduced the severity of colitis through microbiota-dependent and microbiota-independent mechanisms. Combinatorial perturbations to dietary casein protein and psyllium fiber in parallel accounted for most variation in gut microbial density and intestinal permeability in unchallenged mice, as well as the severity of DSS-induced colitis; changes in 1 ingredient

C/EBPβ Mediates Growth Hormone-Regulated Expression of Multiple Target Genes

Science.gov (United States)

Cui, Tracy X.; Lin, Grace; LaPensee, Christopher R.; Calinescu, Anda-Alexandra; Rathore, Maanjot; Streeter, Cale; Piwien-Pilipuk, Graciela; Lanning, Nathan; Jin, Hui; Carter-Su, Christin; Qin, Zhaohui S.

2011-01-01

Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein β (C/EBPβ). This study examines the role of C/EBPβ in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBPβ depletion using short hairpin RNA impaired responsiveness of these genes to GH, as seen for c-Fos. Rescue with wild-type C/EBPβ led to GH-dependent recruitment of the coactivator p300 to the c-Fos promoter. In contrast, rescue with C/EBPβ mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBPβ at T188 is required for GH-induced recruitment of p300 to c-Fos. GH also induced the occupancy of phosphorylated C/EBPβ and p300 on Cyr61, Btg2, and Socs3 at predicted C/EBP-cAMP response element-binding protein motifs in their promoters. Consistent with a role for ERKs in GH-induced expression of these genes, treatment with U0126 to block ERK phosphorylation inhibited their GH-induced expression. In contrast, GH-dependent expression of Zfp36 and Socs1 was not inhibited by U0126. Thus, induction of multiple early response genes by GH in 3T3-F442A cells is mediated by C/EBPβ. A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBPβ, and recruitment of p300. Overall, these studies suggest that C/EBPβ, like the signal transducer and activator of transcription proteins, regulates multiple genes in response to GH. PMID:21292824

Piroxicam and C-phycocyanin mediated apoptosis in 1,2-dimethylhydrazine dihydrochloride induced colon carcinogenesis: exploring the mitochondrial pathway.

Science.gov (United States)

Saini, Manpreet Kaur; Sanyal, Sankar Nath; Vaiphei, Kim

2012-04-01

Apoptosis is a synchronized procedure of cell death that is regulated by caspases and proapoptotic proteins. During apoptosis, translocation of cytochrome c, an electron carrier, from mitochondria into the cytosol is regulated by Bcl-2 family members. Cytochrome c in association with an apoptotic protease activating factor (Apaf), a proapoptotic protein essential for cell differentiation and procaspase-9 form the apoptosome complex, which consecutively activates effector caspase, caspase-3, and coordinate the implementation of apoptosis. In the current study, an attempt has been made to gain insight into piroxicam, a traditional nonsteroidal antiinflammatory drug and c-phycocyanin, a biliprotein from Spirulina platensis (cyanobacterium) mediated apoptosis in DMH-induced colon cancer. Male Sprague-Dawley rats were segregated into 5 groups: control, DMH, DMH + piroxicam, DMH + c-phycocyanin, and DMH + piroxicam + c-phycocyanin. Results illustrated that piroxicam and c-phycocyanin treatments stimulate cytochrome c release by downregulating the Bcl-2 (an antiapoptotic protein) expression significantly, while promoting the level of Bax (a proapoptotic protein), thereby activating caspases (caspases-9 and -3) and Apaf-1. The outcomes of the present study clearly signify that piroxicam and c-phycocyanin may mediate mitochondrial-dependent apoptosis in DMH-induced colon cancer. Moreover, apoptosis induction was more apparent in the combination regimen of piroxicam and c-phycocyanin than the individual drugs alone.

Effects of interleukin-7/interleukin-7 receptor on RANKL-mediated osteoclast differentiation and ovariectomy-induced bone loss by regulating c-Fos/c-Jun pathway.

Science.gov (United States)

Zhao, Ji-Jun; Wu, Zhao-Feng; Yu, Ying-Hao; Wang, Ling; Cheng, Li

2018-09-01

To explore the effects of IL-7/IL-7R on the RANKL-mediated osteoclast differentiation in vitro and OVX-induced bone loss in vivo. BMMs and RAW264.7 were transfected with IL-7, IL-7R siRNA, c-Fos siRNA, and c-jun siRNA and later stimulated by RANKL. TRAP and toluidine blue staining were used to observe osteoclast formation and bone resorption, respectively. HE and TRAP staining were used to detect trabecular bone microstructure and osteoclasts of mice, respectively. qRT-PCR and Western blot analysis were used to examine expression. IL-7 unregulated the expression of CTSK, NFATc1, MMP9, and the phosphorylation of p38 and Akt by activating the c-Fos/c-Jun pathway, which increased osteoclast numbers and bone resorption in RANKL-stimulated macrophages. While IL-7R siRNA and c-Fos siRNA decreased the expression, as well as and the phosphorylation of p38 and Akt.IL-7 decreased the BMD and OPG expression in OVX-induced mice and increased the TRAP positive cells, the mRNA expression of c-fos, c-jun, and RANKL, which was contradictory to IL-7R siRNA, and c-Fos siRNA. Furthermore, IL-7R siRNA and c-Fos siRNA caused thicker trabeculae, increased trabecular number, and decreased osteolysis in OVX mice. IL-7/IL-7R can promote RANKL-mediated osteoclast formation and bone resorption by activating the c-Fos/c-Jun pathway, as well as inducing bone loss in OVX mice. © 2018 Wiley Periodicals, Inc.

Creep behaviour of a short-fibre C/PPS composite

Czech Academy of Sciences Publication Activity Database

Fíla, T.; Koudelka_ml., Petr; Kytýř, Daniel; Hos, J.; Šleichrt, J.

2016-01-01

Roč. 50, č. 3 (2016), s. 413-417 ISSN 1580-2949 R&D Projects: GA TA ČR(CZ) TA03010209 Institutional support: RVO:68378297 Keywords : creep * short fibre composite * C/PPS * Findley’s model * DIC Subject RIV: JI - Composite Materials Impact factor: 0.436, year: 2016 http://mit.imt.si/Revija/izvodi/mit163/fila.pdf

A study comparing the efficacy of antimicrobial agents versus enzyme (P-gp) inducers in the treatment of 2,4,6 trinitrobenzenesulfonic acid-induced colitis in rats.

Science.gov (United States)

Toklu, H Z; Kabasakal, L; Imeryuz, N; Kan, B; Celikel, C; Cetinel, S; Orun, O; Yuksel, M; Dulger, G A

2013-08-01

The intestinal microflora is an important cofactor in the pathogenesis of intestinal inflammation; and the epithelial cell barrier function is critical in providing protection against the stimulation of mucosal immune system by the microflora. In the present study, therapeutic role of the antibacterial drugs rifampicin and ciprofloxacine were investigated in comparison to spironolactone, an enzyme inducer, in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis of the rats. Drugs were administered for 14 days following induction of colitis. All drug treatments ameliorated the clinical hallmarks of colitis as determined by body weight loss and assessment of diarrhea, colon length, and histology. Oxidative damage and neutrophil infiltration as well as nuclear factor κB (NF-κB) and tumor necrosis factor α (TNF-α) expressions that were increased during colitis, were decreased significantly. Rifampicin and ciprofloxacin were probably effective due to their antibacterial and immunomodulating properties. The multidrug resistence gene (MDR1) and its product p-glycoprotein (P-gp) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). In the present study, findings of the P-gp expression were inconclusive but regarding previous studies, it can be suggested that the beneficial effects of rifampicin and spironolactone may be partly due to their action as a P-gp ligand. Spironolactone has been reported to supress the transcription of proinflamatory cytokines that are considered to be of importance in immunoinflammatory diseases. It is also a powerful pregnane X receptor (PXR) inducer; thus, inhibition of the expression of NF-κB and TNF-α, and amelioration of inflammation by spironolactone suggest that this may have been through the activation of PXR. However, our findings regarding PXR expression were inconclusive. Activation of PXR by spironolactone probably also contributed to the induction of P-gp, resulting in extrusion of noxious substances

Thermal detection thresholds of Aδ- and C-fibre afferents activated by brief CO2 laser pulses applied onto the human hairy skin.

Directory of Open Access Journals (Sweden)

Maxim Churyukanov

Full Text Available Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO(2 laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C and C-fibres (39.8±1.7°C. Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively.

Electron beam irradiation in natural fibres reinforced polymers (NFRP)

Energy Technology Data Exchange (ETDEWEB)

Kechaou, B. [LaMaCoP - Faculte des sciences de Sfax, 3018 Sfax (Tunisia); LTDS-UMR 5513 - Ecole Centrale de Lyon, B.P 163 69134 Ecully Cedex (France); Salvia, M. [LTDS-UMR 5513 - Ecole Centrale de Lyon, B.P 163 69134 Ecully Cedex (France); Fakhfakh, Z. [LaMaCoP - Faculte des sciences de Sfax, 3018 Sfax (Tunisia); Juve, D. [LTDS-UMR 5513 - Ecole Centrale de Lyon, B.P 163 69134 Ecully Cedex (France); Boufi, S. [LSME-Faculte des Sciences de Sfax, 3018 Sfax (Tunisia); Kallel, A. [LaMaCoP - Faculte des sciences de Sfax, 3018 Sfax (Tunisia); Treheux, D. [LTDS-UMR 5513 - Ecole Centrale de Lyon, B.P 163 69134 Ecully Cedex (France)], E-mail: daniel.treheux@ec-lyon.fr

2008-11-15

This study focuses on the electric charge motion in unsatured polyester and epoxy composites reinforced by natural fibres of Alfa type, treated by different coupling agents. The electric charging phenomenon is studied by scanning electron microscopy mirror effect (SEMME) coupled with the induced current method (ICM). Previously, using the same approach, glass fibre reinforced epoxy (GFRE) was studied to correlate mechanical [B. Kchaou, C. Turki, M. Salvia, Z. Fakhfakh, D. Treheux, Composites Science and Technology 64 (2004) 1467], or tribological [B. Kchaou, C. Turki, M. Salvia, Z. Fakhfakh, D. Treheux, Dielectric and friction behaviour of unidirectionalglass fibre reinforced epoxy (GFRE), Wear, 265 (2008) 763.] properties and dielectric properties. It was shown that the dielectric properties of the fibre-matrix interfaces play a significant role in the optimization of the composite. This result seems to be the same for natural fibre composites: the fibre-matrix interfaces allow a diffusion of the electric charges which can delocalize the polarization energy and consequently delay the damage of the composite. However, a non-suited sizing can lead to a new trapping of electric charges along these same interfaces with, as a consequence, a localization of the polarisation energy. The optimum composite is obtained for one sizing which helps, at the same time, to have a strong fibre-matrix adhesion and an easy flow of the electric charges along the interface.

Selenoprotein P in colitis-associated carcinoma

Science.gov (United States)

Short, Sarah P.; Whitten-Barrett, Caitlyn; Williams, Christopher S.

2016-01-01

ABSTRACT Patients with inflammatory bowel disease are often deficient in micronutrients such as selenium and have an increased risk of colon cancer. We tested whether the selenium transport protein, selenoprotein P, could modify colitis-associated cancer. Our results indicate that global SEPP1 haploinsufficiency augments tumorigenesis and mediates oxidative damage in the intestine. PMID:27314080

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...

Navy and black bean supplementation attenuates colitis-associated inflammation and colonic epithelial damage.

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Monk, Jennifer M; Wu, Wenqing; Hutchinson, Amber L; Pauls, Peter; Robinson, Lindsay E; Power, Krista A

2018-02-27

The enriched levels of nondigestible fermentable carbohydrates and phenolic compounds found in common beans can exert immunomodulatory effects within the colon that improve gut health and mitigate the severity of colitis-associated inflammatory pathology. Prior to acute colitis onset, C57Bl/6 mice were prefed isocaloric 20% cooked navy bean (NB) or black bean (BB) diets for 3 weeks and switched to control basal diet (BD) 24 h prior to colitis induction via 5-day exposure to dextran sodium sulfate (2% w/v in drinking water)+3 days of fresh water. The severity of the acute colitis phenotype was attenuated by bean prefeeding, evidenced by reduced colon tissue inflammatory transcription factor activation (NFκB, STAT3) and inflammatory mediator levels in the colon (IL-1β, IL-6, IL-18 and MCP-1) and serum (TNFα, IL-6, IL-1β, MCP-1) versus BD (P≤.05). Additionally, biomarkers of enhanced wound repair responses were increased by bean prefeeding including colon tissue protein levels of IL-22, IL-27 and activated (i.e., GTP-bound) Cdc42 and Rac1 versus BD (P≤.05). mRNA expressions of genes involved in normal colonic epithelial function and the promotion of epithelial barrier integrity, defense and/or restitution and wound closure including MUC1, RELMβ, IgA and REG3γ were all increased in NB and BB prefed mice versus BD (P≤.05). Collectively, bean supplementation prior to colitis induction (i.e., mimicking disease relapse) primes the colonic microenvironment to attenuate the severity of the colitis inflammatory phenotype and maintain aspects of epithelial barrier function. Copyright © 2018 Elsevier Inc. All rights reserved.

Anti-inflammatory effect of Helichrysum oligocephalum DC extract on acetic acid - Induced acute colitis in rats

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Mohsen Minaiyan

2014-01-01

Full Text Available Background: Helichrysum oligocephalum DC. from Asteraceae family is an endemic plant growing wild in Iran. This study was carried out to investigate the effect of H. oligocephalum hydroalcoholic extract (HOHE on ulcerative colitis (UC induced by acetic acid (AA in rats. Materials and Methods: Rats were grouped (n = 6 and fasted for 24 h before colitis induction. Treatments were started 2 h before the induction of colitis and continued for two consecutive days with different doses of HOHE (100, 200, and 400 mg/kg orally (p.o. and intraperitoneally (i.p.. The colon tissue was removed and tissue damages were scored after macroscopic and histopathologic assessments. Results: Among the examined doses of HOHE, 100 mg/kg was the most effective dose that reduced the extent of UC lesions and resulted in significant alleviation. Weight/length ratio as an index of tissue inflammation and extravasation was also diminished in the treatment group administered HOHE at a dose of 100 mg/kg, and the results showed correlation with macroscopic and histopathologic evaluations. These data suggest that HOHE (100 mg/kg administered either p.o. or i.p. was effective in diminishing inflammation and ulcer indices in this murine model of acute colitis in a non-dose-related manner. Conclusions: H. oligocephalum could be considered as a suitable anticolitis alternative; however, further studies are needed to support this hypothesis for clinical setting.

Severe ischemic colitis following olanzapine use: a Case Report

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Samuel Raimundo Fernandes

Full Text Available Ischemic colitis is the most common subtype of intestinal ischemia usually resulting from vasospasm, vessel occlusion or mesenteric hypoperfusion. Neuroleptics have seldom been linked to ischemic colitis by blocking peripheral anticholinergic and antiserotonergic receptors inducing severe gastrointestinal paresis. We report a young patient with severe ischemic colitis requiring surgery due to necrosis of the bowel. After exclusion of other potential causes, olanzapine was admitted as the cause of ischemia. Clinicians should be aware of how to recognize and treat the potentially life-threatening effects of neuroleptics.

Anti-inflammatory effect of Helichrysum oligocephalum DC extract on acetic acid — Induced acute colitis in rats

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Minaiyan, Mohsen; Ghassemi-Dehkordi, Nasrollah; Mahzouni, Parvin; Ahmadi, Najme-Sadat

2014-01-01

Background: Helichrysum oligocephalum DC. from Asteraceae family is an endemic plant growing wild in Iran. This study was carried out to investigate the effect of H. oligocephalum hydroalcoholic extract (HOHE) on ulcerative colitis (UC) induced by acetic acid (AA) in rats. Materials and Methods: Rats were grouped (n = 6) and fasted for 24 h before colitis induction. Treatments were started 2 h before the induction of colitis and continued for two consecutive days with different doses of HOHE (100, 200, and 400 mg/kg) orally (p.o.) and intraperitoneally (i.p.). The colon tissue was removed and tissue damages were scored after macroscopic and histopathologic assessments. Results: Among the examined doses of HOHE, 100 mg/kg was the most effective dose that reduced the extent of UC lesions and resulted in significant alleviation. Weight/length ratio as an index of tissue inflammation and extravasation was also diminished in the treatment group administered HOHE at a dose of 100 mg/kg, and the results showed correlation with macroscopic and histopathologic evaluations. These data suggest that HOHE (100 mg/kg) administered either p.o. or i.p. was effective in diminishing inflammation and ulcer indices in this murine model of acute colitis in a non–dose-related manner. Conclusions: H. oligocephalum could be considered as a suitable anticolitis alternative; however, further studies are needed to support this hypothesis for clinical setting. PMID:24761395

Lactobacillus reuteri increases mucus thickness and ameliorates dextran sulphate sodium-induced colitis in mice.

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Ahl, D; Liu, H; Schreiber, O; Roos, S; Phillipson, M; Holm, L

2016-08-01

The aim of this study was to investigate whether two Lactobacillus reuteri strains (rat-derived R2LC and human-derived ATCC PTA 4659 (4659)) could protect mice against colitis, as well as delineate the mechanisms behind this protection. Mice were given L. reuteri R2LC or 4659 by gavage once daily for 14 days, and colitis was induced by addition of 3% DSS (dextran sulphate sodium) to drinking water for the last 7 days of this period. The severity of disease was assessed through clinical observations, histological evaluation and ELISA measurements of myeloperoxidase (MPO) and pro-inflammatory cytokines from colonic samples. Mucus thickness was measured in vivo with micropipettes, and tight junction protein expression was assessed using immunohistochemistry. Colitis severity was significantly reduced by L. reuteri R2LC or 4659 when evaluated both clinically and histologically. The inflammation markers MPO, IL-1β, IL-6 and mKC (mouse keratinocyte chemoattractant) were increased by DSS and significantly reduced by the L. reuteri strains. The firmly adherent mucus thickness was reduced by DSS, but significantly increased by L. reuteri in both control and DSS-treated mice. Expression of the tight junction proteins occludin and ZO-1 was significantly increased in the bottom of the colonic crypts by L. reuteri R2LC. These results demonstrate that each of the two different L. reuteri strains, one human-derived and one-rat-derived, protects against colitis in mice. Mechanisms behind this protection could at least partly be explained by the increased mucus thickness as well as a tightened epithelium in the stem cell area of the crypts. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Protective Effect of Daikenchuto on Dextran Sulfate Sodium-Induced Colitis in Mice.

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Matsunaga, Takaharu; Hashimoto, Shinichi; Yamamoto, Naoki; Kawasato, Ryo; Shirasawa, Tomohiro; Goto, Atsushi; Fujisawa, Koichi; Takami, Taro; Okamoto, Takeshi; Nishikawa, Jun; Sakaida, Isao

2017-01-01

Aim . To investigate the effect of daikenchuto (TJ-100; DKT) for ulcerative colitis (UC) model mouse and assess its anti-inflammatory mechanisms. Methods . We evaluated the effects of DKT on dextran sulfate sodium- (DSS-) induced experimental colitis. First, we assessed the short-term effects of DKT using two groups: 5% DSS group and 5% DSS with DKT group. Colon length; histological scores; and interleukin- (IL-) 10, IL-1 β , and tumor necrosis factor- α mRNA expression profiles were analyzed using real-time PCR. Second, we assessed the long-term effects of DKT, by comparing survival time between 2% DSS and 2% DSS with DKT groups. Results . After 7 days, the colon lengths of DSS + DKT group were longer than those of the DSS group (mean values: 6.11 versus 5.69 cm, p DKT group maintained significantly higher levels of serum hemoglobin (13.1 versus 10.7 g/dL, p DKT group exhibited significantly longer survival time than the 2% DSS group (70 versus 44 days, p DKT prevented inflammation in the colon, indicating its potential as a new therapeutic agent for UC.

cGAS-Mediated Innate Immunity Spreads Intercellularly through HIV-1 Env-Induced Membrane Fusion Sites.

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Xu, Shuting; Ducroux, Aurélie; Ponnurangam, Aparna; Vieyres, Gabrielle; Franz, Sergej; Müsken, Mathias; Zillinger, Thomas; Malassa, Angelina; Ewald, Ellen; Hornung, Veit; Barchet, Winfried; Häussler, Susanne; Pietschmann, Thomas; Goffinet, Christine

2016-10-12

Upon sensing cytoplasmic retroviral DNA in infected cells, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide cGAMP, which activates STING to trigger a type I interferon (IFN) response. We find that membrane fusion-inducing contact between donor cells expressing the HIV envelope (Env) and primary macrophages endogenously expressing the HIV receptor CD4 and coreceptor enable intercellular transfer of cGAMP. This cGAMP exchange results in STING-dependent antiviral IFN responses in target macrophages and protection from HIV infection. Furthermore, under conditions allowing cell-to-cell transmission of HIV-1, infected primary T cells, but not cell-free virions, deliver cGAMP to autologous macrophages through HIV-1 Env and CD4/coreceptor-mediated membrane fusion sites and induce a STING-dependent, but cGAS-independent, IFN response in target cells. Collectively, these findings identify an infection-specific mode of horizontal transfer of cGAMP between primary immune cells that may boost antiviral responses, particularly in infected tissues in which cell-to-cell transmission of virions exceeds cell-free infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypoxia induces cancer-associated cAMP/PKA signalling through HIF-mediated transcriptional control of adenylyl cyclases VI and VII.

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Simko, Veronika; Iuliano, Filippo; Sevcikova, Andrea; Labudova, Martina; Barathova, Monika; Radvak, Peter; Pastorekova, Silvia; Pastorek, Jaromir; Csaderova, Lucia

2017-08-31

Hypoxia is a phenomenon often arising in solid tumours, linked to aggressive malignancy, bad prognosis and resistance to therapy. Hypoxia-inducible factor-1 has been identified as a key mediator of cell and tissue adaptation to hypoxic conditions through transcriptional activation of many genes involved in glucose metabolism and other cancer-related processes, such as angiogenesis, cell survival and cell invasion. Cyclic adenosine 3'5'-monophosphate is one of the most ancient and evolutionarily conserved signalling molecules and the cAMP/PKA signalling pathway plays an important role in cellular adaptation to hypoxia. We have investigated possible new mechanisms behind hypoxic activation of the cAMP/PKA pathway. For the first time, we have shown that hypoxia induces transcriptional up-regulation of the system of adenylyl cyclases, enzymes responsible for cAMP production, in a panel of carcinoma cell lines of various origin. Our data prove functional relevance of the hypoxic increase of adenylyl cyclases VI and VII at least partially mediated by HIF-1 transcription factor. We have identified adenylyl cyclase VI and VII isoforms as mediators of cellular response to hypoxia, which led to the elevation of cAMP levels and enhanced PKA activity, with an impact on cell migration and pH regulation.

Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis

KAUST Repository

Arsenescu, Violeta

2011-04-11

Background: Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn\\'s disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis. Methods: C57BL/6 mice were injected (i.v.) with an adenoviral construct encoding the full-length murine adiponectin gene (AN+DSS) or a reporter-LacZ (Ctr and V+DSS groups) prior to DSS colitis protocol. In another experiment, mice with DSS colitis received either osmotin (Osm+DSS) or saline (DSS) via osmotic pumps. Disease progression and severity were evaluated using body weight, stool consistency, rectal bleeding, colon lengths, and histology. In vitro experiments were carried out in bone marrow-derived dendritic cells. Results: Mice overexpressing adiponectin had lower expression of proinflammatory cytokines (TNF, IL-1β), adipokines (angiotensin, osteopontin), and cellular stress and apoptosis markers. These mice had higher levels of IL-10, alternative macrophage marker, arginase 1, and leukoprotease inhibitor. The plant adiponectin homolog osmotin similarly improved colitis outcome and induced robust IL-10 secretion. LPS induced a state of adiponectin resistance in dendritic cells that was reversed by treatment with PPARγ agonist and retinoic acid. Conclusion: Adiponectin exerted protective effects during murine DSS colitis. It had a broad activity that encompassed cytokines, chemotactic factors as well as processes that assure cell viability during stressful conditions. Reducing adiponectin resistance or using plant-derived adiponectin homologs may become therapeutic options in inflammatory bowel disease. © 2011 Springer Science+Business Media, LLC.

Simultaneous Onset of Ulcerative Colitis and Disseminated Pyoderma Gangrenosum

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Albrecht Neesse

2007-10-01

Full Text Available Pyoderma gangrenosum (PG is an immune-mediated inflammatory skin condition representing one of the most distinct extraintestinal manifestations of inflammatory bowel disease (IBD. PG occurs independently from intestinal disease activity in about 1–2% of patients suffering from ulcerative colitis or Crohn’s disease and is characterized by chronic deep skin ulcers whose exact pathogenesis is still unknown. So far, patients with ulcerative colitis have only been reported to develop PG during the course of IBD but not at the initial manifestation of bowel symptoms. This is the first report demonstrating the simultaneous onset of ulcerative colitis and severe multifocal PG. In addition, we provide first evidence that infliximab may have a particularly powerful effect in early disseminated PG compared to late-onset PG, advocating an early application of this drug.

Celecoxib prevents colitis associated colon carcinogenesis: an upregulation of apoptosis.

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Setia, Shruti; Nehru, Bimla; Sanyal, Sankar N

2014-12-01

Uncontrolled cell proliferation and suppressed apoptosis are the critical events transforming a normal cell to a cancerous one wherein the inflammatory microenvironment supports this oncogenic transformation. The process of colon carcinogenesis may be aggravated in chronic inflammatory conditions such as ulcerative colitis where non-steroidal anti-inflammatory drugs (NSAIDs) may effectively prevent the cellular and molecular events. Western blots and immunofluorescent analysis of DNA mismatch repair enzymes, cell cycle regulators and pro- and anti-apoptotic proteins were performed in dextran sulfate sodium (DSS)-induced ulcerative colitis and 1,2-dimethyl benz(a)anthracene (DMH)-induced colon cancer. Also, apoptotic studies were done in isolated colonocytes using fluorescent staining and in paraffin sections using TUNEL assay. An upregulation of cell cycle regulators: cyclin D1/cdk4 and cyclin E/cdk2 and anti-apoptotic Bcl-2, along with the suppression of DNA repair enzymes: MLH1 and MSH2; tumour suppressors: p53, p21and Rb and pro-apoptotic proteins: Bax and Bad were observed in the DSS, DMH and DSS+DMH groups. Proliferating cell nuclear antigen (PCNA) was also overexpressed in these groups. The ultimate executioner of the apoptotic pathway; caspase-3, was suppressed in these groups. Apoptotic studies in colonocytes and paraffin sections revealed suppressed apoptosis in these groups. These effects were corrected with the administration of a second generation NSAID, celecoxib along with the treatment of DSS and DMH. The chemopreventive action of celecoxib in colitis mediated colon carcinogenesis may include the regulation of DNA mismatch repair enzymes, cell cycle check points, cell proliferation and apoptosis. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Ceramide Production Mediates Aldosterone-Induced Human Umbilical Vein Endothelial Cell (HUVEC Damages.

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Yumei Zhang

Full Text Available Here, we studied the underlying mechanism of aldosterone (Aldo-induced vascular endothelial cell damages by focusing on ceramide. We confirmed that Aldo (at nmol/L inhibited human umbilical vein endothelial cells (HUVEC survival, and induced considerable cell apoptosis. We propose that ceramide (mainly C18 production might be responsible for Aldo-mediated damages in HUVECs. Sphingosine-1-phosphate (S1P, an anti-ceramide lipid, attenuated Aldo-induced ceramide production and following HUVEC damages. On the other hand, the glucosylceramide synthase (GCS inhibitor PDMP or the ceramide (C6 potentiated Aldo-induced HUVEC apoptosis. Eplerenone, a mineralocorticoid receptor (MR antagonist, almost completely blocked Aldo-induced C18 ceramide production and HUVEC damages. Molecularly, ceramide synthase 1 (CerS-1 is required for C18 ceramide production by Aldo. Knockdown of CerS-1 by targeted-shRNA inhibited Aldo-induced C18 ceramide production, and protected HUVECs from Aldo. Reversely, CerS-1 overexpression facilitated Aldo-induced C18 ceramide production, and potentiated HUVEC damages. Together, these results suggest that C18 ceramide production mediates Aldo-mediated HUVEC damages. MR and CerS-1 could be the two signaling molecule regulating C18 ceramide production by Aldo.

High Extinction Ratio In-Fibre Polarisers by Exploiting Tilted Fibre Bragg Grating Structures for Single-Polarisation High-Power Fibre Lasers and Amplifiers

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2009-11-01

maintaining (PM) fibre, utilising polarisation hole-burning ( PHB ) effect to reduce homogeneous linewidth of the EDFL. In our work, we demonstrate a stable...loss filter which will induce some loss to the cavity around its paired attenuation band region, thus imposing PHB effect to the gain medium. The...polarisation-hole-burning ( PHB ) effect to realise multi-wavelength switchable function in proposed fibre ring laser system. In the proposed fibre ring laser

Action of arginine for protection of ulcerative colitis by dextran sodium sulphate (DSS)

International Nuclear Information System (INIS)

Andrade, Maria Emilia Rabelo

2016-01-01

Recent studies have demonstrated the benefits of immunomodulators, such as arginine, in the regulation of inflammatory responses and trophism of the intestinal mucosa. The aim of this study was to evaluate the possible mechanisms action of arginine (pretreatment or treatment) in experimental model of ulcerative colitis induced by dextran sodium sulfate (DSS). C57BL/6 mice were randomized into 5 groups: Control group (C): standard diet and water; Arginine group (ARG): diet supplementation with arginine and water; Colitis group (COL): standard diet and DSS solution; Pretreated group (PT): diet supplementation with arginine before and during colitis induction; Treated group (T): diet supplementation with arginine during colitis induction. Colitis was induced by administration of 1.5% DSS for 5 days. After this, all the mice were euthanized and blood, organs and intestinal fluid were collected for carrying out analyzes. Parameters such as intestinal permeability (IP), bacterial translocation (BT), histological analysis (histological score, morphometric analysis, collagen and mucins stain), nitrate and nitrite, cytokines and chemokines, secretory immunoglobulin A (sIgA), inflammatory infiltrate and oxidative stress were performed. The ARG group did not show difference compared to group C in the investigated parameters (C vs ARG: p> 0.05). The COL group showed increased IP (C vs COL: p < 0.05) and BT (C vs COL: p <0.05). In the histological analysis, the COL group showed severe inflammation and reduction the crypts length. In addition, in the group COL observed increase infiltration of eosinophils, neutrophils and macrophages in the colon, increase cytokine IL-17 and chemokine KC in serum and oxidative stress in the colon (COL vs C: p <0.05). In the arginine-supplemented groups (PT and T) was observed decrease IP and BT to blood, liver and lung (PT and T vs Col: p <0.05). Histological analysis showed that the arginine (PT and T) preserved the intestinal mucosa and crypts

Salmon cartilage proteoglycan suppresses mouse experimental colitis through induction of Foxp3+ regulatory T cells

International Nuclear Information System (INIS)

Mitsui, Toshihito; Sashinami, Hiroshi; Sato, Fuyuki; Kijima, Hiroshi; Ishiguro, Yoh; Fukuda, Shinsaku; Yoshihara, Shuichi; Hakamada, Ken-Ichi; Nakane, Akio

2010-01-01

Research highlights: → Salmon proteoglycan suppresses IL-10 -/- cell transfer-induced colitis progression. → Salmon proteoglycan suppresses Th1- and Th17-related factors in colitis mice. → 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) -/- mice. IL-10 -/- 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-γ, IL-12, TNF-α, IL-21, IL-23p19, IL-6, IL-17A and retinoic acid-related orphan receptor γt (RORγt) in lamina propria mononuclear cells (LPMCs) and oral administration of PG suppressed the expression of these factors. Conversely, expression of Foxp3 that induces CD4 + CD25 + 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.

Immunotherapy-Induced Colitis: An Emerging Problem for the Hospitalist.

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Marin-Acevedo, Julian A; Harris, Dana M; Burton, M Caroline

2018-06-01

Since their introduction for melanoma treatment, the use of immune checkpoint inhibitors (ICIs) has rapidly expanded. Though their impact on survival is irrefutable, these medications have been associated with autoimmune-like adverse events related to their ability to induce the immune system. One of the most commonly affected organ systems is the gastrointestinal (GI) tract, in which manifestations range from mild diarrhea to severe colitis with intestinal perforation. Because of the increased use of ICIs, hospitalists are caring for an increasing number of patients experiencing their adverse events. We present a case-oriented review of the GI adverse events associated with the use of ICIs to familiarize the hospitalist with their mechanism of action and potential complications and to emphasize the importance of early diagnosis and treatment to decrease morbidity and mortality. © 2018 Society of Hospital Medicine.

Seven-core active fibre for application in telecommunication satellites

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Filipowicz, Marta; Napierała, Marek; Murawski, Michał; Ostrowski, Łukasz; Szostkiewicz, Łukasz; Szymański, Michał; Tenderenda, Tadeusz; Anders, Krzysztof; Piramidowicz, Ryszard; Wójcik, Grzegorz; Makara, Mariusz; Poturaj, Krzysztof; Mergo, Paweł; Nasiłowski, Tomasz

2015-12-01

The use of optical elements and other photonic components makes it possible to overcome telecommunication satellite's bottleneck problems such as size and weight reduction. Despite the unquestionable potential of such elements, nowadays they are not widely used in systems operating in space. This is due to many factors, including the fact that space radiation has disruptive influence on optical fibre. Namely it introduces additional radiation induced attenuation (RIA) that significantly lowers efficiency of optical fibre based systems. However, there is a possibility to produce radiation-hardened (rad-hard) components. One of them is seven core erbium-doped active fibre (MC-EDF) for fibre amplifiers in satellites that we have been developing. In this paper we present a detailed description of seven core structure design as well as experimental results. We report that average gain of 20 dB in C-band with noise figure of 5.8 dB was obtained. We also confirmed that low crosstalk value for a multicore fibre amplifier based on our fibre can be achieved.

The effect of stinging nettle (Urtica dioica) seed oil on experimental colitis in rats.

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Genc, Zeynep; Yarat, Aysen; Tunali-Akbay, Tugba; Sener, Goksel; Cetinel, Sule; Pisiriciler, Rabia; Caliskan-Ak, Esin; Altıntas, Ayhan; Demirci, Betul

2011-12-01

This study investigated the effect of Urtica dioica, known as stinging nettle, seed oil (UDO) treatment on colonic tissue and blood parameters of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Experimental colitis was induced with 1 mL of TNBS in 40% ethanol by intracolonic administration with a 8-cm-long cannula with rats under ether anesthesia, assigned to a colitis group and a colitis+UDO group. Rats in the control group were given saline at the same volume by intracolonic administration. UDO (2.5 mL/kg) was given to the colitis+UDO group by oral administration throughout a 3-day interval, 5 minutes later than colitis induction. Saline (2.5 mL/kg) was given to the control and colitis groups at the same volume by oral administration. At the end of the experiment macroscopic lesions were scored, and the degree of oxidant damage was evaluated by colonic total protein, sialic acid, malondialdehyde (MDA), and glutathione levels, collagen content, tissue factor activity, and superoxide dismutase and myeloperoxidase activities. Colonic tissues were also examined by histological and cytological analysis. Pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), lactate dehydrogenase activity, and triglyceride and cholesterol levels were analyzed in blood samples. We found that UDO decreased levels of pro-inflammatory cytokines, lactate dehydrogenase, triglyceride, and cholesterol, which were increased in colitis. UDO administration ameliorated the TNBS-induced disturbances in colonic tissue except for MDA. In conclusion, UDO, through its anti-inflammatory and antioxidant actions, merits consideration as a potential agent in ameliorating colonic inflammation.

An antibiotic-responsive mouse model of fulminant ulcerative colitis.

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Silvia S Kang

2008-03-01

Full Text Available BACKGROUND: The constellation of human inflammatory bowel disease (IBD includes ulcerative colitis and Crohn's disease, which both display a wide spectrum in the severity of pathology. One theory is that multiple genetic hits to the host immune system may contribute to the susceptibility and severity of IBD. However, experimental proof of this concept is still lacking. Several genetic mouse models that each recapitulate some aspects of human IBD have utilized a single gene defect to induce colitis. However, none have produced pathology clearly distinguishable as either ulcerative colitis or Crohn's disease, in part because none of them reproduce the most severe forms of disease that are observed in human patients. This lack of severe IBD models has posed a challenge for research into pathogenic mechanisms and development of new treatments. We hypothesized that multiple genetic hits to the regulatory machinery that normally inhibits immune activation in the intestine would generate more severe, reproducible pathology that would mimic either ulcerative colitis or Crohn's disease. METHODS AND FINDINGS: We generated a novel mouse line (dnKO that possessed defects in both TGFbetaRII and IL-10R2 signaling. These mice rapidly and reproducibly developed a disease resembling fulminant human ulcerative colitis that was quite distinct from the much longer and more variable course of pathology observed previously in mice possessing only single defects. Pathogenesis was driven by uncontrolled production of proinflammatory cytokines resulting in large part from T cell activation. The disease process could be significantly ameliorated by administration of antibodies against IFNgamma and TNFalpha and was completely inhibited by a combination of broad-spectrum antibiotics. CONCLUSIONS: Here, we develop to our knowledge the first mouse model of fulminant ulcerative colitis by combining multiple genetic hits in immune regulation and demonstrate that the resulting

Spectral and kinetic analysis of radiation induced optical attenuation in silica: towards intrinsic fibre optic dosimetry?

International Nuclear Information System (INIS)

Borgermans, P.

2002-01-01

The document is an abstract of a PhD thesis. The PhD work concerns the detailed investigation of the behaviour of optical fibres in radiation fields such as is the case for various nuclear and space application,s. The core of the work concerns the spectral and kinetic analysis of the radiation induced optical attenuation. Models describing underlying physical phenomena, both for the spectral and the time dimensions, have been developed. The potential of silica optical fibre waveguides for intrinsic dosimetry has been assessed by employing specific properties of radiation induced defects in the silica waveguide material

Isoliquiritigenin, a flavonoid from licorice, blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE{sub 2} and IL-6

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Zhao, Haixia [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhang, Xinhua [Department of Liver, Biliary And Pancreatic Tumors, Hubei Cancer Hospital, Wuhan 430079 (China); Chen, Xuewei; Li, Ying; Ke, Zunqiong [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Guo, Austin M. [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Department of Pharmacology, New York Medical College, Valhalla, NY 10595 (United States); Chen, Honglei, E-mail: hl-chen@whu.edu.cn [Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China)

2014-09-15

M2 macrophage polarization is implicated in colorectal cancer development. Isoliquiritigenin (ISL), a flavonoid from licorice, has been reported to prevent azoxymethane (AOM) induced colon carcinogenesis in animal models. Here, in a mouse model of colitis-associated tumorigenesis induced by AOM/dextran sodium sulfate (DSS), we investigated the chemopreventive effects of ISL and its mechanisms of action. Mice were treated with AOM/DSS and randomized to receive either vehicle or ISL (3, 15 and 75 mg/kg). Tumor load, histology, immunohistochemistry, and gene and protein expressions were determined. Intragastric administration of ISL for 12 weeks significantly decreased colon cancer incidence, multiplicity and tumor size by 60%, 55.4% and 42.6%, respectively. Moreover, ISL inhibited M2 macrophage polarization. Such changes were accompanied by downregulation of PGE{sub 2} and IL-6 signaling. Importantly, depletion of macrophages by clodronate (Clod) or zoledronic acid (ZA) reversed the effects of ISL. In parallel, in vitro studies also demonstrated that ISL limited the M2 polarization of RAW264.7 cells and mouse peritoneal macrophages with concomitant inactivation of PGE{sub 2}/PPARδ and IL-6/STAT3 signaling. Conversely, exogenous addition of PGE{sub 2} or IL-6, or overexpression of constitutively active STAT3 reversed ISL-mediated inhibition of M2 macrophage polarization. In summary, dietary flavonoid ISL effectively inhibits colitis-associated tumorigenesis through hampering M2 macrophage polarization mediated by the interplay between PGE{sub 2} and IL-6. Thus, inhibition of M2 macrophage polarization is likely to represent a promising strategy for chemoprevention of colorectal cancer. - Highlights: • Isoliquiritigenin (ISL) prevents colitis-associated tumorigenesis. • ISL inhibits M2 macrophage polarization in vivo and in vitro. • ISL inhibits PGE{sub 2} and IL-6 signaling in colitis-associated tumorigenesis. • ISL may be an attractive candidate agent for

The Bile Acid Receptor GPBAR-1 (TGR5) Modulates Integrity of Intestinal Barrier and Immune Response to Experimental Colitis

Science.gov (United States)

Cipriani, Sabrina; Mencarelli, Andrea; Chini, Maria Giovanna; Distrutti, Eleonora; Renga, Barbara; Bifulco, Giuseppe; Baldelli, Franco; Donini, Annibale; Fiorucci, Stefano

2011-01-01

Background GP-BAR1, a member G protein coupled receptor superfamily, is a cell surface bile acid-activated receptor highly expressed in the ileum and colon. In monocytes, ligation of GP-BAR1 by secondary bile acids results in a cAMP-dependent attenuation of cytokine generation. Aims To investigate the role GP-BAR1 in regulating intestinal homeostasis and inflammation-driven immune dysfunction in rodent models of colitis. Methods Colitis was induced in wild type and GP-BAR1−/− mice by DSS and TNBS administration. Potential GP-BAR1 agonists were identified by in silico screening and computational docking studies. Results GP-BAR1−/− mice develop an abnormal morphology of colonic mucous cells and an altered molecular architecture of epithelial tight junctions with increased expression and abnormal subcellular distribution of zonulin 1 resulting in increased intestinal permeability and susceptibility to develop severe colitis in response to DSS at early stage of life. By in silico screening and docking studies we identified ciprofloxacin as a GP-BAR1 ligand. In monocytes, ciprofloxacin increases cAMP concentrations and attenuates TNFα release induced by TLR4 ligation in a GP-BAR1 dependent manner. Treating mice rendered colitic by TNBS with ciprofloxacin and oleanolic acid, a well characterized GP-BAR1 ligand, abrogates signs and symptoms of colitis. Colonic expression of GP-BAR1 mRNA increases in rodent models of colitis and tissues from Crohn's disease patients. Flow cytometry analysis demonstrates that ≈90% of CD14+ cells isolated from the lamina propria of TNBS-treated mice stained positively for GP-BAR1. Conclusions GP-BAR1 regulates intestinal barrier structure. Its expression increases in rodent models of colitis and Crohn's disease. Ciprofloxacin is a GP-BAR1 ligand. PMID:22046243

The bile acid receptor GPBAR-1 (TGR5 modulates integrity of intestinal barrier and immune response to experimental colitis.

Directory of Open Access Journals (Sweden)

Sabrina Cipriani

Full Text Available BACKGROUND: GP-BAR1, a member G protein coupled receptor superfamily, is a cell surface bile acid-activated receptor highly expressed in the ileum and colon. In monocytes, ligation of GP-BAR1 by secondary bile acids results in a cAMP-dependent attenuation of cytokine generation. AIMS: To investigate the role GP-BAR1 in regulating intestinal homeostasis and inflammation-driven immune dysfunction in rodent models of colitis. METHODS: Colitis was induced in wild type and GP-BAR1(-/- mice by DSS and TNBS administration. Potential GP-BAR1 agonists were identified by in silico screening and computational docking studies. RESULTS: GP-BAR1(-/- mice develop an abnormal morphology of colonic mucous cells and an altered molecular architecture of epithelial tight junctions with increased expression and abnormal subcellular distribution of zonulin 1 resulting in increased intestinal permeability and susceptibility to develop severe colitis in response to DSS at early stage of life. By in silico screening and docking studies we identified ciprofloxacin as a GP-BAR1 ligand. In monocytes, ciprofloxacin increases cAMP concentrations and attenuates TNFα release induced by TLR4 ligation in a GP-BAR1 dependent manner. Treating mice rendered colitic by TNBS with ciprofloxacin and oleanolic acid, a well characterized GP-BAR1 ligand, abrogates signs and symptoms of colitis. Colonic expression of GP-BAR1 mRNA increases in rodent models of colitis and tissues from Crohn's disease patients. Flow cytometry analysis demonstrates that ≈90% of CD14+ cells isolated from the lamina propria of TNBS-treated mice stained positively for GP-BAR1. CONCLUSIONS: GP-BAR1 regulates intestinal barrier structure. Its expression increases in rodent models of colitis and Crohn's disease. Ciprofloxacin is a GP-BAR1 ligand.

Association between gastrointestinal motility and macrophage/mast cell distribution in mice during the healing stage after DSS‑induced colitis.

Science.gov (United States)

Kodani, Mio; Fukui, Hirokazu; Tomita, Toshihiko; Oshima, Tadayuki; Watari, Jiro; Miwa, Hiroto

2018-06-01

Irritable bowel syndrome (IBS) frequently occurs after infectious colitis or inflammatory bowel disease in patients with complete remission. This suggests that post‑inflammation‑associated factors may serve a role in the pathophysiology of IBS; however, the mechanism responsible remains unclear. In the present study, the involvement of macrophages and mast cells in alteration of gastrointestinal (GI) motility was investigated in mice in the remission stage after acute colitis. C57BL/6 mice were administered 2% dextran sulfate sodium in drinking water for 5 days and their intestinal tissues were investigated at intervals for up to 24 weeks. Expression of the mannose receptor (MR) and tryptase was examined by immunohistochemistry, and the GI transit time (GITT) was measured by administration of carmine red solution. A minimal degree of inflammatory cell infiltration persisted in the colon and also the small intestine of mice in remission after colitis and the GITT was significantly shorter. The number of muscularis MR‑positive macrophages was significantly increased in the small intestine of mice in remission after colitis and negatively correlated with GITT. Furthermore, results indicated that the number of muscularis tryptase‑positive mast cells was significantly increased throughout the intestine of mice during the healing process after colitis and was positively correlated with GITT. The present findings suggested an increased number of macrophages and/or mast cells in the intestinal muscular layer may be associated with the pathophysiology of GI dysmotility after colitis.

Microanalytical investigation of fibre-reinforced ceramic materials

International Nuclear Information System (INIS)

Meier, B.; Grathwohl, G.

1989-01-01

Microanalytical investigations have been made on samples of ceramic fibres (SiC fibres, (Nicalon) C fibre coated with TiN) and fibre-reinforced ceramics (SiC-and glass-matrices). High resolution Auger electron spectroscopy (HRAES), electron probe microanalysis (EPMA) and scanning electron microscopy were employed for these examinations. Analysis was best performed with HRAES on account of its lateral and depth resolution. Some of the problems involved in this technique are discussed e.g. electron beam effects. AES depth profiles of ceramic fibres are reported and compared with the surface analysis of fibres in the composites after being broken in situ. (orig.)

Thermally induced structural changes in Nomex fibres

Indian Academy of Sciences (India)

Unknown

Abstract. Thermally aged Nomex fibres manifest several residual effects viz. reduction in X-ray crystallinity, weight loss and deterioration in tensile characteristics. Surface damages in the form of longi- tudinal openings, holes, material deposits etc have also been observed. Based on the data from thermally exposed fibres ...

Some fundamental problems relating to optical fibres. II. The ultimate bandwidth performance of optical fibre transmission lines

International Nuclear Information System (INIS)

Gambling, W.A.

1977-01-01

Optical fibre transmission lines can be divided broadly into two types, namely single mode and multimode. The bandwidth of the former is limited by the variation in group velocity with frequency caused by mode dispersion and material dispersion, with predicted values of tens of gigahertz over tens of kilometres for a monochromatic carrier, falling to approximately l GHz over 1km for a typical injection laser. Multimode fibres have the additional limitation of group delay between the various propagating modes. Several schemes have been suggested for reducing this effect, such as: (a) exciting only a few modes (ideally one) in a fibre exhibiting no mode conversion, (b) inducing coupling between bound modes but not into radiating modes, and (c) equalizing the mode velocities by means of a suitable refractive index profile. Most effort is presently being devoted to (c) and it has been shown that the optimum profile is affected by leaky modes and material dispersion. By operating at a wavelength in the region of 1.25μm the effect of material dispersion can be greatly reduced and bandwidths in excess of 1 GHz over 1km might be expected, even with sources of large linewidth. (author)

Modelling of photonic crystal fibres

DEFF Research Database (Denmark)

Knudsen, Erik

2003-01-01

, as well as a honeycomb bandgap fibre and the first analysis of semi-periodic layered air-hole fibres. Using the modelling framework established as a basis, we provide an analysis of microbend loss, by regarding displacement of a fibre core as a stationary stochastic process, inducing mismatch between......In the presenta ph.d. work a theoretical study of aspects of modelling photonic crystal fibres was carried out. Photonic crystal fibres form a class of optical waveguides where guidance is no longer provided by a difference in refractive index between core and cladding. Instead, guidance...... is provided by an arrangement of air-holes running along the length of the fibre. Depending on the geometry of the fibre, the guiding mechanism may be either arising from the formation of a photonic bandgap in the cladding structure (photonic bandgap fibre), or by an effect resembling total internal...

Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis

DEFF Research Database (Denmark)

Soendergaard, Christoffer; Kvist, Peter Helding; Thygesen, Peter

2017-01-01

Growth hormone (GH) resistance may develop as a consequence of inflammation during conditions such as inflammatory bowel disease, encompassing ulcerative colitis (UC). However, the specific role of the GH-insulin growth factor (IGF)-1-axis and/or the functional consequences of GH resistance......) proteins. These effects are driven by pro-inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6) as confirmed using primary epithelial cells. Treatment of experimental colitis with GH increased IGF-1 and body weight of the mice, but had no effects on colonic inflammation...

Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion.

Directory of Open Access Journals (Sweden)

Cinthia Silva-Vilches

Full Text Available Immature or semi-mature dendritic cells (DCs represent tolerogenic maturation stages that can convert naive T cells into Foxp3+ induced regulatory T cells (iTreg. Here we found that murine bone marrow-derived DCs (BM-DCs treated with cholera toxin (CT matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CThi, CTlo or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β. Only DCs matured under CThi conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CTlo- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3+ iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CTlo- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE by inducing Foxp3+ Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae.

Sputter etching of polymer fibres

International Nuclear Information System (INIS)

Carter, G.; Hill, A.E.; Nobes, M.J.; Jeffries, R.; Simmens, S.C.

1979-01-01

Fibres of polyamide, polyester and an aromatic polyamide (Kevlar) have been subjected to Ar + ion bombardment erosion in an ion accelerator or an rf discharge system. In the case of the former two polymers, cones are observed to develop upon the fibre surface and these are associated with etch protection resulting from the presence of particles of titanium dioxide pigment. This effect is absent in the third, unpigmented, fibre. In all cases ripple structures with a habit transverse to the fibre axes and of wavelength of approximately 1000 Angstrom are gradually developed during ion bombardment. It is suggested that this morphology results from an underlying periodicity of the fibre structure either inherent in the fibre structure or induced by the irradiation. (author)

Characterization of Fibre-Direction Dependent Damping of Glass-Fibre Composites at Low Temperatures and Low Frequencies

DEFF Research Database (Denmark)

Kliem, Mathias; Høgsberg, Jan Becker; Dannemann, Martin

2016-01-01

This paper deals with the characterization of the fibre-direction dependent damping capability of glass fibre reinforced plastics (GFRP) to be used in electrical power transmission pylons. A fibre-direction dependent damping analysis of unidirectional (UD) GFRP samples was carried out using...... a Dynamic Mechanical Analysis (DMA) for five different fibre orientations (0˚ | 30˚ | 45˚ | 60˚ and 90˚) and two different matrix systems (epoxy and a vinyl ester resin). Based on the dynamic characteristics the damping performance of the various composite materials was studied at three temperatures (-10˚C......, 0˚C and 10˚C) and three vibration frequencies (1 Hz, 10 Hz and 30 Hz). It was observed that the loss factor of Glass Fibre Reinforced Vinyl-Ester (GF-VE) was in general slightly higher compared to the Glass Fibre Reinforced Epoxy (GF-EP). The loss factor increased slightly with temperature, while...

Damage characterization of E-glass and C-glass fibre polymer composites after high velocity impact

Science.gov (United States)

Razali, N.; Sultan, M. T. H.; Cardona, F.; Jawaid, M.

2017-12-01

The purpose of this work is to identify impact damage on glass fibre reinforced polymer composite structures after high velocity impact. In this research, Type C-glass (600 g/m2) and Type E-glass (600 g/m2) were used to fabricate Glass Fibre-Reinforced Polymer composites (GFRP) plates. The panels were fabricated using a vacuum bagging and hot bounder method. Single stage gas gun (SSGG) was used to do the testing and data acquisition system was used to collect the damage data. Different types of bullets and different pressure levels were used for the experiment. The obtained results showed that the C-glass type of GFRP experienced more damage in comparison to E-glass type of materials based on the amount of energy absorbed on impact and the size of the damage area. All specimens underwent a partial fibre breakage but the laminates were not fully penetrated by the bullets. This indicated that both types of materials have high impact resistance even though the applied pressures of the gas gun were on the high range. We concluded that within the material specifications of the laminates including the type of glass fibre reinforcement and the thickness of the panels, those composite materials are safe to be applied in structural and body armour applications as an alternative to more expensive materials such as Kevlar and type S-glass fibre based panels.

Phrenic motor outputs in response to bronchopulmonary C‐fibre activation following chronic cervical spinal cord injury

Science.gov (United States)

2016-01-01

Key points Activation of bronchopulmonary C‐fibres, the main chemosensitive afferents in the lung, can induce pulmonary chemoreflexes to modulate respiratory activity.Following chronic cervical spinal cord injury, bronchopulmonary C‐fibre activation‐induced inhibition of phrenic activity was exaggerated.Supersensitivity of phrenic motor outputs to the inhibitory effect of bronchopulmonary C‐fibre activation is due to a shift of phrenic motoneuron types and slow recovery of phrenic motoneuron discharge in cervical spinal cord‐injured animals.These data suggest that activation of bronchopulmonary C‐fibres may retard phrenic output recovery following cervical spinal cord injury.The alteration of phenotype and discharge pattern of phrenic motoneuron enables us to understand the impact of spinal cord injury on spinal respiratory activity. Abstract Cervical spinal injury interrupts bulbospinal pathways and results in cessation of phrenic bursting ipsilateral to the lesion. The ipsilateral phrenic activity can partially recover over weeks to months following injury due to the activation of latent crossed spinal pathways and exhibits a greater capacity to increase activity during respiratory challenges than the contralateral phrenic nerve. However, whether the bilateral phrenic nerves demonstrate differential responses to respiratory inhibitory inputs is unclear. Accordingly, the present study examined bilateral phrenic bursting in response to capsaicin‐induced pulmonary chemoreflexes, a robust respiratory inhibitory stimulus. Bilateral phrenic nerve activity was recorded in anaesthetized and mechanically ventilated adult rats at 8–9 weeks after C2 hemisection (C2Hx) or C2 laminectomy. Intra‐jugular capsaicin (1.5 μg kg−1) injection was performed to activate the bronchopulmonary C‐fibres to evoke pulmonary chemoreflexes. The present results indicate that capsaicin‐induced prolongation of expiratory duration was significantly attenuated in C2Hx

Effects of a novel encapsulating technique on the temperature tolerance and anti-colitis activity of the probiotic bacterium Lactobacillus kefiranofaciens M1.

Science.gov (United States)

Wang, Sheng-Yao; Ho, Yi-Fang; Chen, Yen-Po; Chen, Ming-Ju

2015-04-01

Lactobacillus kefiranofaciens M1 (M1) has been shown to possess many different beneficial health effects including anti-colitis activity. The purpose of this study was to develop a novel and easily scaled-up encapsulating technique that would improve the temperature tolerance of the bacterium and reduce the sensitivity of the organism to gastrointestinal fluid. A mixture of sodium alginate, gellan gum and skim milk powder was used as a coating material to entrap M1. The M1 gel was then directly freeze dried in order to dehydrate the covering and form microcapsules. The viable cell numbers of M1 present only dropped ten folds after the freeze-drying encapsulation process. The viable cell counts remained constant at 5 × 10(7) CFU/g after heating from 25 °C to 75 °C and holding at 75 °C for 1 min. The viable cell counts were reduced to 10(6) CFU/g and 10(5) CFU/g after 8-week storage at 4 °C and subsequent heat treatment with simulated gastrointestinal fluid test (SGFT) and bile salts, respectively. The effect of encapsulated M1 on the organism's anti-colitis activity was evaluated using the dextran sodium sulfate (DSS) induced colitis mouse model. An in vivo study indicated that administration of heat treated encapsulated M1 was able to ameliorate DSS-induced colitis producing a significant reduction in the bleeding score and an attenuation of inflammatory score. These findings clearly demonstrate that encapsulation of M1 using this novel technique is able to provide good protection from temperature changes and SGFT treatment and also does not affect the organism's anti-colitis activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fabrication and oxidation resistance of titanium carbide-coated carbon fibres by reacting titanium hydride with carbon fibres in molten salts

International Nuclear Information System (INIS)

Dong, Z.J.; Li, X.K.; Yuan, G.M.; Cong, Y.; Li, N.; Jiang, Z.Y.; Hu, Z.J.

2009-01-01

Using carbon fibres and titanium hydride as a reactive carbon source and a metal source, respectively, a protective titanium carbide (TiC) coating was formed on carbon fibres in molten salts, composed of LiCl-KCl-KF, at 750-950 o C. The structure and morphology of the TiC coatings were characterised by X-ray diffraction and scanning electron microscopy, respectively. The oxidation resistance of the TiC-coated carbon fibres was measured by thermogravimetric analysis. The results reveal that control of the coating thickness is very important for improvement of the oxidation resistance of TiC-coated carbon fibres. The oxidative weight loss initiation temperature for the TiC-coated carbon fibres increases significantly when an appropriate coating thickness is used. However, thicker coatings lead to a decrease of the carbon fibres' weight loss initiation temperature due to the formation of cracks in the coating. The TiC coating thickness on carbon fibres can be controlled by adjusting the reaction temperature and time of the molten salt synthesis.

Non-IBD and noninfectious colitis

DEFF Research Database (Denmark)

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

2008-01-01

, 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...

Melatonin reduces the expression of chemokines in rat with trinitrobenzene sulfonic acid-induced colitis

International Nuclear Information System (INIS)

Li, Jun H.; Zhou, W.; Liu, K.; Li, Hong X.; Wang, L.

2008-01-01

Objective was to investigate the effect of melatonin on the colon inflammatory injury of rats with colitis and determine whether this effect is associated with inhibition of chemoattractant molecules interleukins (IL-8) and monocyte chemoattractant protein (MCP)-1.The study was designed and implemented in JingMen No.1 People's Hospital, HuBei Province, from May 2006 to April 2007. It involved 72 animals divided into 6 groups of 12 each: normal group, model group, 5-aminosalisalicylic acid group, and melatonin group (dose of 2.5, 5.0 and 10.0mg/kg). Rat colitis model was established by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) enema. Interleukin-8 and MCP-1 proteins in colon tissue were examined by immunohistochemistry and western blot. The messenger-RNA expressions of chemokines were determined by reverse transcription polymerase chain reaction analysis. Trinitrobenzene sulfonic acid enema resulted in pronounced pathological changes of colonic mucosa in model rats, which were in accordance with the significantly elevated Myeloperoxidase activity. Expressions of chemokines were up-regulated in colitis. Melatonin treatment reduced colonic lesions and improved colitis symptom, and decreased the protein and mRNA expressions of IL-8 and MCP-1 significantly in colon tissues of rats with colitis. Chemokines IL-8 and MCP-1 are elevated in mucosal tissues in colitis and play an important role in the perpetuation of tissue destructive inflammatory process; melatonin reduces colonic inflammatory injury of rats colitis through down-regulating the expressions of chemokines. Melatonin can be considered as a novel therapeutic alternative for the treatment of inflammatory bowel disease. (author)

Superoxide dismutase recombinant Lactobacillus fermentum ameliorates intestinal oxidative stress through inhibiting NF-κB activation in a trinitrobenzene sulphonic acid-induced colitis mouse model.

Science.gov (United States)

Hou, C L; Zhang, J; Liu, X T; Liu, H; Zeng, X F; Qiao, S Y

2014-06-01

Superoxide dismutase (SOD) can prevent and cure inflammatory bowel diseases by decreasing the amount of reactive oxygen species. Unfortunately, short half-life of SOD in the gastrointestinal tract limited its application in the intestinal tract. This study aimed to investigate the treatment effects of recombinant SOD Lactobacillus fermentum in a colitis mouse model. In this study, we expressed the sodA gene in Lact. fermentum I5007 to obtain the SOD recombinant strain. Then, we determined the therapeutic effects of this SOD recombinant strain in a trinitrobenzene sulphonic acid (TNBS)-induced colitis mouse model. We found that SOD activity in the recombinant Lact. fermentum was increased by almost eightfold compared with that in the wild type. Additionally, both the wild type and the recombinant Lact. fermentum increased the numbers of lactobacilli in the colon of mice (P < 0·05). Colitis mice treated with recombinant Lact. fermentum showed a higher survival rate and lower disease activity index (P < 0·05). Recombinant Lact. fermentum significantly decreased colonic mucosa histological scoring for infiltration of inflammatory cells, lipid peroxidation, the expression of pro-inflammatory cytokines and myeloperoxidase (P < 0·05) and inhibited NF-κB activity in colitis mice (P < 0·05). SOD recombinant Lact. fermentum significantly reduced oxidative stress and inflammation through inhibiting NF-κB activation in the TNBS-induced colitis model. This study provides insights into the anti-inflammatory effects of SOD recombinant Lact. fermentum, indicating the potential therapeutic effects in preventing and curing intestinal bowel diseases. © 2014 The Society for Applied Microbiology.

Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but not gelatinase activities.

Science.gov (United States)

Direito, Rosa; Lima, Ana; Rocha, João; Ferreira, Ricardo Boavida; Mota, Joana; Rebelo, Patrícia; Fernandes, Adelaide; Pinto, Rui; Alves, Paula; Bronze, Rosário; Sepodes, Bruno; Figueira, Maria-Eduardo

2017-08-01

Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging and antiinflammatory activities; however, little is known about the effects of persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Therefore, we aimed in this work to characterize the antiinflammatory and antiproliferative effects of a persimmon phenolic extract (80% acetone in water), using an in vivo model of experimental colitis and a model of cancer cell invasion. Our results show, for the first time, a beneficial effect of a persimmon phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells. Administration of persimmon phenolic extract to mice with TNBS-induced colitis led to a reduction in several functional and histological markers of colon inflammation, namely: attenuation of colon length decrease, reduction of the extent of visible injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate, reduction of mucosal hemorrhage and reduction of general histological features of colon inflammation. In vitro studies also showed that persimmon phenolic extract successfully impaired cell proliferation and invasion in HT-29 cells. Further investigation showed a decreased expression of COX-2 and iNOS in the colonic tissue of colitis mice, two important mediators of intestinal inflammation, but there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the role of inflammatory processes in the progression of CRC and the important link between inflammation and cancer, our results highlight the potential of persimmon polyphenols as a pharmacological tool in the treatment of patients with IBD. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Genetic deletion of IL-25 (IL-17E) confers resistance to dextran sulfate sodium-induced colitis in mice

Science.gov (United States)

IL-25 is emerging as a key regulator of inflammation in the intestinal mucosa because of its ability to promote Th2 while suppressing Th1 and Th17 cytokine responses. We investigated the contribution of endogenous IL-25 to DSS-induced colitis in mice. Mice were exposed to DSS in drinking water ad li...

Polarisation Control of DFB Fibre Laser Using UV-Induced Birefringent Phase-Shift

DEFF Research Database (Denmark)

Philipsen, Jacob Lundgreen; Lauridsen, Vibeke Claudia; Berendt, Martin Ole

1998-01-01

The polarisation properties of a distributed feedback (DFB) fibre laser are investigated experimentally. A birefringent phase-shift is induced by side illumination of the centre part of the lasing structure with ultraviolet (UV) light and it is experimentally shown that the birefringence...... of the phase-shift is the dominating effect controlling the polarisation properties of the laser....

Selective up-regulation of NMDA-NR1 receptor expression in myenteric plexus after TNBS induced colitis in rats

Directory of Open Access Journals (Sweden)

Price Donald D

2006-01-01

Full Text Available Abstract Background N-methyl-D-aspartic acid (NMDA spinal cord receptors play an important role in the development of hyperalgesia following inflammation. It is unclear, however, if changes in NMDA subunit receptor gene expression in the colonic myenteric plexus are associated with colonic inflammation. We investigated regulation of NMDA-NR1 receptor gene expression in TNBS induced colitis in rats. Male Sprague-Dawley rats (150 g–250 g were treated with 20 mg trinitrobenzene sulfonic acid (TNBS diluted in 50% ethanol. The agents were delivered with a 24 gauge catheter inserted into the lumen of the colon. The animals were sacrificed at 2, 7, 14, 21, and 28 days after induction of the colitis, their descending colon was retrieved for reverse transcription-polymerase chain reaction; a subset of animals' distal colon was used for two-dimensional (2-D western analysis and immunocytochemistry. Results NR1-exon 5 (N1 and NR1-exon 21 (C1 appeared 14, 21 and 28 days after TNBS treatment. NR1 pan mRNA was up-regulated at 14, 21, and 28 days. The NR1-exon 22 (C2 mRNA did not show significant changes. Using 2-D western analysis, untreated control rats were found to express only NR1001 whereas TNBS treated rats expressed NR1001, NR1011, and NR1111. Immunocytochemistry demonstrated NR1-N1 and NR1-C1 to be present in the myenteric plexus of TNBS treated rats. Conclusion These results suggest a role for colonic myenteric plexus NMDA receptors in the development of neuronal plasticity and visceral hypersensitivity in the colon. Up-regulation of NMDA receptor subunits may reflect part of the basis for chronic visceral hypersensitivity in conditions such as post-infectious irritable bowel syndrome.

Diagnosis and management of microscopic colitis: current perspectives

Directory of Open Access Journals (Sweden)

Bohr J

2014-08-01

Full Text Available Johan Bohr,1,3 Anna Wickbom,1,3 Agnes Hegedus,2 Nils Nyhlin,1,3 Elisabeth Hultgren Hörnquist,3 Curt Tysk1,3 1Division of Gastroenterology, Department of Medicine, 2Department of Laboratory Medicine/Pathology, Örebro University Hospital, Örebro, 3School of Health and Medical Sciences, Örebro University, Örebro, Sweden Abstract: Collagenous colitis and lymphocytic colitis, together constituting microscopic colitis, are common causes of chronic diarrhea. They are characterized clinically by chronic nonbloody diarrhea and a macroscopically normal colonic mucosa where characteristic histopathological findings are seen. Previously considered rare, they now have emerged as common disorders that need to be considered in the investigation of the patient with chronic diarrhea. The annual incidence of each disorder is five to ten per 100,000 inhabitants, with a peak incidence in 60- to 70-year-old individuals and a predominance of female patients in collagenous colitis. The etiology and pathophysiology are not well understood, and the current view suggests an uncontrolled mucosal immune reaction to various luminal agents in predisposed individuals. Clinical symptoms comprise chronic diarrhea, abdominal pain, fatigue, weight loss, and fecal incontinence that may impair the patient's health-related quality of life. An association is reported with other autoimmune disorders, such as celiac disease, thyroid disorders, diabetes mellitus, and arthritis. The best-documented treatment, both short-term and long-term, is budesonide, which induces clinical remission in up to 80% of patients after 8 weeks' treatment. However, after successful budesonide therapy is ended, recurrence of clinical symptoms is common, and the best possible long-term management deserves further study. The long-term prognosis is good, and the risk of complications, including colonic cancer, is low. We present an update of the epidemiology, pathogenesis, diagnosis, and management of

Fibre Bragg grating encapted with no-core fibre sensors for SRI and temperature monitoring

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S. Daud

2018-06-01

Full Text Available In this work, a Fibre Bragg grating (FBG encapted with no-core fibre (NCF as surrounding refractive index (SRI and temperature sensors are practically demonstrated. A FBG with 1550 nm wavelength was attached with 5 cm length of no-core fibre (NCF is used as SRI and temperature sensing probe. The change of temperature and SRI induced the wavelength shift in FBG. The wavelength shift in FBG reacts directly proportional to the temperature with a sensitivity of while the sensitivity of NCF was measured as 13.13 pm °C−1. Keywords: FBG, No-core fibre (NCF, Temperature, Sensor

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

Directory of Open Access Journals (Sweden)

Aguilar-Nascimento J.E.

1999-01-01

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

Prebiotics and synbiotics in ulcerative colitis.

Science.gov (United States)

Laurell, Axel; Sjöberg, Klas

2017-04-01

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with unclear pathogenesis. A dysbiotic intestinal microbiota is regarded as a key component in the disease process and there has been significant interest in developing new treatments which target the microbiota. To give an overview of the studies to date investigating prebiotics and synbiotics for the treatment of UC. A literature search of PubMed and related search engines was carried out using the terms "ulcerative colitis" in combination with "prebiotic", "synbiotic" or "dietary fibre". In total 17 studies on humans examining the effect of prebiotics in UC were found. Five major groups could be distinguished. Fructo-oligosaccharides were tried in six studies (mean 35 patients included, range 9-121). One study found a clinical response while two demonstrated indirect evidence of an effect. Germinated barley foodstuff was used in 8 studies (mean 38 patients, range 10-63). One study found an endoscopic response, while four noted a clinical response and two some indirect effects. Galacto-oligosaccharides, lactulose and resveratrol were used in one study each (mean 48 patients, range 41-52). One study found an endoscopic response and one a clinical response. There is yet inadequate evidence - especially in humans - to support any particular prebiotic in the clinical management of UC. However, due to the bulk of evidence supporting the effect of the microbiota on colonic inflammation, there is enough potential to justify further high-quality clinical trials investigating this subject.

Protective Effect of Daikenchuto on Dextran Sulfate Sodium-Induced Colitis in Mice

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Takaharu Matsunaga

2017-01-01

Full Text Available Aim. To investigate the effect of daikenchuto (TJ-100; DKT for ulcerative colitis (UC model mouse and assess its anti-inflammatory mechanisms. Methods. We evaluated the effects of DKT on dextran sulfate sodium- (DSS- induced experimental colitis. First, we assessed the short-term effects of DKT using two groups: 5% DSS group and 5% DSS with DKT group. Colon length; histological scores; and interleukin- (IL- 10, IL-1β, and tumor necrosis factor-α mRNA expression profiles were analyzed using real-time PCR. Second, we assessed the long-term effects of DKT, by comparing survival time between 2% DSS and 2% DSS with DKT groups. Results. After 7 days, the colon lengths of DSS + DKT group were longer than those of the DSS group (mean values: 6.11 versus 5.69 cm, p<0.05. Furthermore, compared to DSS group, the DSS + DKT group maintained significantly higher levels of serum hemoglobin (13.1 versus 10.7 g/dL, p<0.05 and exhibited significantly higher expression levels of IL-10 (p<0.05. The 2% DSS + DKT group exhibited significantly longer survival time than the 2% DSS group (70 versus 44 days, p<0.01. Conclusion. Our results indicate that DKT prevented inflammation in the colon, indicating its potential as a new therapeutic agent for UC.

IL-9 antibody injection suppresses the inflammation in colitis mice

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Yuan, Aping [Laboratory of Molecular Cell Biology, Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås (Norway); Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan (China); Yang, Hang; Qi, Haili; Cui, Jing; Hua, Wei; Li, Can; Pang, Zhigang; Zheng, Wei [Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan (China); Cui, Guanglin, E-mail: guanglin.cui@yahoo.com [Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan (China); Faculty of Health, Nord University at Levanger (Norway)

2015-12-25

Diverse T help (Th) cells play a crucial role in the processing and maintaining of chronic inflammation as seen in ulcerative colitis (UC). Th9, a novel subset of Th cells that primarily produces interleukin (IL)-9, has recently been associated with the development of inflammatory diseases. In this study, we evaluated the presentation of Th9 cells in inflamed tissues of human and experimental mouse UC, and examined the therapeutic efficiency of anti Th9 cytokine IL-9 in the experimental mouse UC. Using immunohistochemistry (IHC), we evaluated the presentation of Th9 cells labelled by transcriptional factor PU.1 in both human and dextran sulfate sodium (DSS) induced mouse colitis biopsies. The results showed that increased PU.1 positive Th9 cells were mainly located in the lamina propria in relative with the controls, intraepithelial Th9 cells can also be observed but at low density. Double IHCs revealed that most of PU.1 positive cells were CD3 positive lymphocytes in human UC specimens. Anti-IL-9 antibody injection for 2 weeks reduced the severity of inflammation in DSS induced colitis mice. Our results suggest that The Th9/IL-9 is involved in the pathogenesis of UC. - Highlights: • The density of novel PU.1 positive Th9 cells is significantly increased in both human and mouse colitis tissues. • PU.1 positive Th9 cells are predominately located in the inflamed lamina propria in both human and mouse colitis tissues. • Blocking of Th9 cytokine IL-9 by antibody injection suppresses the severity of inflammation in the bowel in colitis mice. • Novel Th9 cells contribute to the pathogenesis of UC.

IL-9 antibody injection suppresses the inflammation in colitis mice

International Nuclear Information System (INIS)

Yuan, Aping; Yang, Hang; Qi, Haili; Cui, Jing; Hua, Wei; Li, Can; Pang, Zhigang; Zheng, Wei; Cui, Guanglin

2015-01-01

Diverse T help (Th) cells play a crucial role in the processing and maintaining of chronic inflammation as seen in ulcerative colitis (UC). Th9, a novel subset of Th cells that primarily produces interleukin (IL)-9, has recently been associated with the development of inflammatory diseases. In this study, we evaluated the presentation of Th9 cells in inflamed tissues of human and experimental mouse UC, and examined the therapeutic efficiency of anti Th9 cytokine IL-9 in the experimental mouse UC. Using immunohistochemistry (IHC), we evaluated the presentation of Th9 cells labelled by transcriptional factor PU.1 in both human and dextran sulfate sodium (DSS) induced mouse colitis biopsies. The results showed that increased PU.1 positive Th9 cells were mainly located in the lamina propria in relative with the controls, intraepithelial Th9 cells can also be observed but at low density. Double IHCs revealed that most of PU.1 positive cells were CD3 positive lymphocytes in human UC specimens. Anti-IL-9 antibody injection for 2 weeks reduced the severity of inflammation in DSS induced colitis mice. Our results suggest that The Th9/IL-9 is involved in the pathogenesis of UC. - Highlights: • The density of novel PU.1 positive Th9 cells is significantly increased in both human and mouse colitis tissues. • PU.1 positive Th9 cells are predominately located in the inflamed lamina propria in both human and mouse colitis tissues. • Blocking of Th9 cytokine IL-9 by antibody injection suppresses the severity of inflammation in the bowel in colitis mice. • Novel Th9 cells contribute to the pathogenesis of UC.

Oxidation resistance in air of 1-D SiC (Hi-nicalon) fibre reinforced silicon nitride ceramic matrix composite

International Nuclear Information System (INIS)

Dupel, P.; Veyret, J.B.

1997-01-01

The oxidation behaviour of a Si 3 N 4 matrix reinforced with SiC fibres (Hi-nicalon) pre-coated with a 400 nm thick pyrolytic carbon layer has been investigated in dry air in the temperature range 800-1500 C. The same study was performed for individual constituents of the composite (fibre and matrix). Two phenomena are observed in the oxidation behaviour of the composite. At low temperature (T<1200 C), the matrix oxidation is negligible, only the carbon interphase was oxidised creating an annular space between the fibres and the matrix throughout the sample. At high temperature (T≥1300 C) the rate of formation of the oxidation products of the matrix is rapid and a sealing effect is observed. While at these temperatures the interphase is protected in the bulk of the material, the time needed to seal the gap between the fibre and the matrix is too long to prevent its oxidation to a significant depth from the surface. Finally, preliminary results are presented where the consumption of the interphase is completely prevented by applying an external coating which gives oxidation protection from low to high temperature. (orig.)

Portulaca Extract Attenuates Development of Dextran Sulfate Sodium Induced Colitis in Mice through Activation of PPARγ.

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Kong, Rui; Luo, Hui; Wang, Nan; Li, Jingjing; Xu, Shizan; Chen, Kan; Feng, Jiao; Wu, Liwei; Li, Sainan; Liu, Tong; Lu, Xiya; Xia, Yujing; Shi, Yanhong; Zhou, Yingqun; He, Weigang; Dai, Qi; Zheng, Yuejuan; Lu, Jie

2018-01-01

Portulaca oleracea L. is a traditional Chinese medicine, which has been used as adjuvant therapy for inflammatory bowel disease (IBD). However, the mechanism of its activity in IBD still remains unclear. Since previous studies have documented the anti-inflammatory effect of peroxisome proliferator activated receptors- γ (PPAR- γ ), Portulaca regulation of PPAR- γ in inflammation was examined in current study. Ulcerative colitis (UC) was generated by 5% dextran sulfate sodium (DSS) in mice and four groups were established as normal control, DSS alone, DSS plus mesalamine, and DSS plus Portulaca . Severity of UC was evaluated by body weight, stool blood form, and length of colorectum. Inflammation was examined by determination of inflammatory cytokines (TNF-a, IL-6, and IL-1a). Portulaca extract was able to attenuate development of UC in DSS model similar to the treatment of mesalazine. Moreover, Portulaca extract inhibited proinflammatory cytokines release and reduced the level of DSS-induced NF- κ B phosphorylation. Furthermore, Portulaca extract restored PPAR- γ level, which was reduced by DSS. In addition, Portulaca extract protected DSS induced apoptosis in mice. In conclusion, Portulaca extract can alleviate colitis in mice through regulation of inflammatory reaction, apoptosis, and PPAR- γ level; therefore, Portulaca extract can be a potential candidate for the treatment of IBD.

Fibre optics cabling design for LHC detectors upgrade using variable radiation induced attenuation model

CERN Document Server

Shoaie, Mohammad Amin; Machado, Simao; Ricci, Daniel

2018-01-01

Foreseen upgrades over the next decades enable LHC to operate at a higher luminosity (HL-LHC). Accordingly, the optical links designed to transmit particle collision data need to be hardened against increased radiation level, allowing for a reliable communication. In this paper we study the fibre cabling design of a link between the transceiver optical front-end and the data control room. The radiation penalty calculation takes temperature drop down to ‒30°C into account. The proposed solution concatenates radiation-resistance and conventional fibres using multi-fibre interconnections. The end-to-end link loss during HL-LHC lifetime is estimated strictly less than 3.5 dB complying with predefined margin.

Effects of a high fat or a balanced omega 3/omega 6 diet on cytokines levels and DNA damage in experimental colitis.

Science.gov (United States)

Vieira de Barros, Karina; Gomes de Abreu, Gilclay; Xavier, Roberta Araujo Navarro; Real Martinez, Carlos Augusto; Ribeiro, Marcelo Lima; Gambero, Alessandra; de Oliveira Carvalho, Patrícia; Silveira, Vera Lúcia Flor

2011-02-01

High-fat diets have been shown to be a risk factor for ulcerative colitis (UC). Omega-6 polyunsaturated fatty acids are considered to increase lipid peroxidation, while the omega-3 polyunsaturated fatty acid exerts a chemopreventative effect. We evaluated the effect of high-fat diets (20%) enriched with fish or soybean oil on colonic inflammation and DNA damage in dextran sulfate sodium-induced colitis. Male Wistar rats (28-30 days) were fed an American Institute of Nutrition (AIN)-93 diet for 47 days and divided into five groups: control normal fat non-colitic (C) or control colitis (CC), high soybean fat group (HS) colitis, high fish fat group colitis, or high-fat soybean plus fish oil colitis. UC was induced from day 35 until day 41 by 3% dextran sulfate sodium. On day 47, the rats were anesthetized; blood samples collected for corticosterone determination, and the distal colon was excised to quantify interleukin-4 (IL-4), IL-10, and interferon-gamma levels, myeloperoxidase activity, histological analyses, and DNA damage. The disease activity index was recorded daily. The disease activity index, histological analysis, myeloperoxidase activity, IL-4, interferon-gamma, and corticosterone levels did not differ among the colitic groups. IL-10 was significantly increased by the high fish fat group diet in relation to HS, but only the high soybean-fish fat diet increased the IL-10/IL-4 ratio (anti-inflammatory/pro-inflammatory) to levels closer to the C group and reduced DNA damage compared to the HS group (Pdiets did not exacerbate UC and suggest that the soybean and fish oil mixture, more than the fish oil alone, could be a complementary therapy to achieve a cytokine balance in UC. Copyright © 2011 Elsevier Inc. All rights reserved.

Determination of CTOD C in Fibre Metal Laminates by ASTM and Schwalbe Methods

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E.M. Castrodeza

2002-06-01

Full Text Available Fibre Metal Laminates (FMLs have arisen as a demand of the aeronautical industry to use thin sheets with high resistance to fatigue crack growth, high damage tolerance, corrosion resistance and high specific strength. Considering these requirements, FMLs are an advantageous choice when compared to metal alloys currently used. In order to employ FMLs in aircraft structures, designers must hold a deep knowledge of a wide set of their properties including fracture toughness. The aim of this work was to evaluate the available methodologies to measure fracture toughness at instability (CTOD C in unidirectional fibre metal laminates reinforced with aramid fibres (ARALL®. To achieve this, tests were performed to obtain traditional and Schwalbe CTODs by using experimental ASTM based techniques, especially adapted to these laminates. Results achieved point out that Schwalbe method is more appropriate and also that there are differences between both CTOD parameters.

T-helper 17 and interleukin-17-producing lymphoid tissue inducer-like cells make different contributions to colitis in mice.

Science.gov (United States)

Ono, Yuichi; Kanai, Takanori; Sujino, Tomohisa; Nemoto, Yasuhiro; Kanai, Yasumasa; Mikami, Yohei; Hayashi, Atsushi; Matsumoto, Atsuhiro; Takaishi, Hiromasa; Ogata, Haruhiko; Matsuoka, Katsuyoshi; Hisamatsu, Tadakazu; Watanabe, Mamoru; Hibi, Toshifumi

2012-11-01

T helper (Th) 17 cells that express the retinoid-related orphan receptor (ROR) γt contribute to the development of colitis in mice, yet are found in normal and inflamed intestine. We investigated their development and functions in intestines of mice. We analyzed intestinal Th17 cells in healthy and inflamed intestinal tissues of mice. We analyzed expression of lymphotoxin (LT)α by Th17 cells and lymphoid tissue inducer-like cells. LTα(-/-) and RORγt(-/-) mice had significantly lower percentages of naturally occurring Th17 cells in the small intestine than wild-type mice. Numbers of CD3(-)CD4(+/-)interleukin-7Rα(+)c-kit(+)CCR6(+)NKp46(-) lymphoid tissue inducer-like cells that produce interleukin-17A were increased in LTα(-/-) and LTα(-/-) × recombination activating gene (RAG)-2(-/-) mice, compared with wild-type mice, but were absent from RORγt(-/-) mice. Parabiosis of wild-type and LTα(-/-) mice and bone marrow transplant experiments revealed that LTα-dependent gut-associated lymphoid tissue structures are required for generation of naturally occurring Th17 cells. However, when wild-type or LTα(-/-) CD4(+)CD45RB(high) T cells were transferred to RAG-2(-/-) or LTα(-/-)×RAG-2(-/-) mice, all groups, irrespective of the presence or absence of LTα on the donor or recipient cells, developed colitis and generated Th1, Th17, and Th17/Th1 cells. RAG-2(-/-) mice that received a second round of transplantation, with colitogenic but not naturally occurring Th17 cells, developed intestinal inflammation. The presence of naturally occurring Th17 cells in the colons of mice inhibited development of colitis after transfer of CD4(+)CD45RB(high) T cells and increased the numbers of Foxp3(+) cells derived from CD4(+)CD45RB(high) T cells. Gut-associated lymphoid tissue structures are required to generate naturally occurring Th17 cells that have regulatory activities in normal intestines of mice, but not for colitogenic Th17 and Th17/Th1 cells during inflammation

Compaction in optical fibres and fibre Bragg gratings under nuclear reactor high neutron and gamma fluence

Energy Technology Data Exchange (ETDEWEB)

Remy, L.; Cheymol, G. [CEA, French Nuclear Energy Commission, Nuclear Energy Division, DPC/SEARS/LISL Bat 467 CEA Saclay 91191 Gif/Yvette Cedex (France); Gusarov, A. [SCK.CEN - Belgian Nuclear Research center, Boeretang 200 2400 Mol (Belgium); Morana, A.; Marin, E.; Girard, S. [Universite de Saint-Etienne, Laboratoire Hubert Curien, UMR CNRS5516, 18, rue du Pr. Lauras, F-42000 Saint-Etienne (France)

2015-07-01

In the framework of the development by CEA and SCK.CEN of a Fabry Perot Sensor (FPS) able to measure dimensional changes in Material Testing Reactor (MTR), the first goal of the SAKE 1 (Smirnof extention - Additional Key-tests on Elongation of glass fibres) irradiation was to measure the linear compaction of single mode fibres under high fast neutron fluence. Indeed, the compaction of the fibre which forms one side of the Fabry Perot cavity, may in particular cause a noticeable measurement error. An accurate quantification of this effect is then required to predict the radiation-induced drift and optimize the sensor design. To achieve this, an innovative approach was used. Approximately seventy uncoated fibre tips (length: 30 to 50 mm) have been prepared from several different fibre samples and were installed in the SCK.CEN BR2 reactor (Mol Belgium). After 22 days of irradiation a total fast (E > 1 MeV) fluence of 3 to 5x10{sup 19} n{sub fast}/cm{sup 2}, depending on the sample location, was accumulated. The temperature during irradiation was 291 deg. C, which is not far from the condition of the intended FPS use. A precise measurement of each fibre tip length was made before the irradiation and compared to the post irradiation measurement highlighting a decrease of the fibres' length corresponding to about 0.25% of linear compaction. The amplitude of the changes is independent of the capsule, which could mean that the compaction effect saturates even at the lowest considered fluence. In the prospect of performing distributed temperature measurement in MTR, several fibre Bragg gratings written using a femtosecond laser have been also irradiated. All the gratings were written in radiation hardened fibres, and underwent an additional treatment with a procedure enhancing their resistance to ionizing radiations. A special mounting made it possible to test the reflection and the transmission of the gratings on fibre samples cut down to 30 to 50 mm. The comparison

Physical and antioxidant properties of gluten-free bread enriched with carob fibre

Science.gov (United States)

Różyło, Renata; Dziki, Dariusz; Gawlik-Dziki, Urszula; Biernacka, Beata; Wójcik, Monika; Ziemichód, Alicja

2017-07-01

There are no reports of addition of carob fibre to gluten-free bread, as only carob germ flour was used. The research task was to determine what level of carob fibre can be used and how it influences the physical and sensorial properties of gluten-free bread. Especially, the knowledge of the antioxidant properties of such bread is very valuable. The gluten-free bread from rice, corn, and buckwheat flour (35:35:30%) was prepared after mixing (5 min), proofing (40 min, 30°C), and baking (45-50 min, 230°C) of dough. Carob fibre was added in the amounts of 1, 2, 3, 4, and 5% of the total flour content. The results showed that increased content of carob fibre induced significant and favourable changes in the volume, colour, and texture (hardness and springiness) of the bread crumb. Carob fibre enriched the breads with lipophilic compounds able to chelate metal ions. The activity of hydrophilic compounds was significantly higher in the case of control bread and bread with the lowest percentage of the additive. In conclusion, the highest increase in antioxidant activity was found for breads with 1 and 2% of carob fibre. The most acceptable gluten-free bread can be obtained by adding up to 2% of carob.

Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility.

Directory of Open Access Journals (Sweden)

Joshua M Uronis

2009-06-01

Full Text Available It is well established that the intestinal microbiota plays a key role in the pathogenesis of Crohn's disease (CD and ulcerative colitis (UC collectively referred to as inflammatory bowel disease (IBD. Epidemiological studies have provided strong evidence that IBD patients bear increased risk for the development of colorectal cancer (CRC. However, the impact of the microbiota on the development of colitis-associated cancer (CAC remains largely unknown. In this study, we established a new model of CAC using azoxymethane (AOM-exposed, conventionalized-Il10(-/- mice and have explored the contribution of the host intestinal microbiota and MyD88 signaling to the development of CAC. We show that 8/13 (62% of AOM-Il10(-/- mice developed colon tumors compared to only 3/15 (20% of AOM- wild-type (WT mice. Conventionalized AOM-Il10(-/- mice developed spontaneous colitis and colorectal carcinomas while AOM-WT mice were colitis-free and developed only rare adenomas. Importantly, tumor multiplicity directly correlated with the presence of colitis. Il10(-/- mice mono-associated with the mildly colitogenic bacterium Bacteroides vulgatus displayed significantly reduced colitis and colorectal tumor multiplicity compared to Il10(-/- mice. Germ-free AOM-treated Il10(-/- mice showed normal colon histology and were devoid of tumors. Il10(-/-; Myd88(-/- mice treated with AOM displayed reduced expression of Il12p40 and Tnfalpha mRNA and showed no signs of tumor development. We present the first direct demonstration that manipulation of the intestinal microbiota alters the development of CAC. The TLR/MyD88 pathway is essential for microbiota-induced development of CAC. Unlike findings obtained using the AOM/DSS model, we demonstrate that the severity of chronic colitis directly correlates to colorectal tumor development and that bacterial-induced inflammation drives progression from adenoma to invasive carcinoma.

Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis

Science.gov (United States)

Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases: Crohn disease and ulcerative colitis. Dietary n-6 fatty acids have been associated with ulcetative colitis in prospective studies. However, the critical d...

Dual Role of Vitamin C on the Neuroinflammation Mediated Neurodegeneration and Memory Impairments in Colchicine Induced Rat Model of Alzheimer Disease.

Science.gov (United States)

Sil, Susmita; Ghosh, Tusharkanti; Gupta, Pritha; Ghosh, Rupsa; Kabir, Syed N; Roy, Avishek

2016-12-01

The neurodegeneration in colchicine induced AD rats (cAD) is mediated by cox-2 linked neuroinflammation. The importance of ROS in the inflammatory process in cAD has not been identified, which may be deciphered by blocking oxidative stress in this model by a well-known anti-oxidant vitamin C. Therefore, the present study was designed to investigate the role of vitamin C on colchicine induced oxidative stress linked neuroinflammation mediated neurodegeneration and memory impairments along with peripheral immune responses in cAD. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus of cAD. Administration of vitamin C (200 and 400 mg/kg BW) in cAD resulted in recovery of memory impairments, with prevention of neurodegeneration and neuroinflammation in the hippocampus. The neuroinflammation in the hippocampus also influenced the peripheral immune responses and inflammation in the serum of cAD and all of these parameters were also recovered at 200 and 400 mg dose of vitamin C. However, cAD treated with 600 mg dose did not recover but resulted in increase of memory impairments, neurodegeneration and neuroinflammation in hippocampus along with alteration of peripheral immune responses in comparison to cAD of the present study. Therefore, the present study showed that ROS played an important role in the colchicine induced neuroinflammation linked neurodegeneration and memory impairments along with alteration of peripheral immune responses. It also appears from the results that vitamin C at lower doses showed anti-oxidant effect and at higher dose resulted in pro-oxidant effects in cAD.

Simplifying the design of microstructured optical fibre pressure sensors.

Science.gov (United States)

Osório, Jonas H; Chesini, Giancarlo; Serrão, Valdir A; Franco, Marcos A R; Cordeiro, Cristiano M B

2017-06-07

In this paper, we propose a way to simplify the design of microstructured optical fibres with high sensitivity to applied pressure. The use of a capillary fibre with an embedded core allows the exploration of the pressure-induced material birefringence due to the capillary wall displacements and the photoelastic effect. An analytical description of pressure-induced material birefringence is provided, and fibre modal characteristics are explored through numerical simulations. Moreover, a capillary fibre with an embedded core is fabricated and used to probe pressure variations. Even though the embedded-core fibre has a non-optimized structure, measurements showed a pressure sensitivity of (1.04 ± 0.01) nm/bar, which compares well with more complex, specially designed fibre geometries reported in the literature. These results demonstrate that this geometry enables a novel route towards the simplification of microstructured fibre-based pressure sensors.

Hemp fibres: Enzymatic effect of microbial processing on fibre bundle structure

DEFF Research Database (Denmark)

Thygesen, Anders; Liu, Ming; Meyer, Anne S.

2013-01-01

The effects of microbial pretreatment on hemp fibres were evaluated after microbial retting using the white rot fungi Ceriporiopsis subvermispora and Phlebia radiata Cel 26 and water retting. Based on chemical composition, P. radiata Cel 26 showed the highest selectivity for pectin and lignin...... degradation and lowest cellulose loss (14%) resulting in the highest cellulose content (78.4%) for the treated hemp fibres. The pectin and lignin removal after treatment with P. radiata Cel 26 were of the order 82% and 50%, respectively. Aligned epoxy-matrix composites were made from hemp fibres defibrated...... with the microbial retting to evaluate the effects on their ultrastructure. SEM microscopy of the composites showed low porosity on the fibre surfaces after defibration with P. radiata Cel 26 and C. subvermispora indicating good epoxy polymer impregnation. In contrast, fibres treated by water retting and the raw...

Corrosion induced strain monitoring through fibre optic sensors

International Nuclear Information System (INIS)

Grattan, S K T; Basheer, P A M; Taylor, S E; Zhao, W; Sun, T; Grattan, K T V

2007-01-01

The use of strain sensors is commonplace within civil engineering. Fibre optic strain sensors offer a number of advantages over the current electrical resistance type gauges. In this paper the use of fibre optic strain sensors and electrical resistance gauges to monitor the production of corrosion by-products has been investigated and reported

Recent advances in poled optical fibres

DEFF Research Database (Denmark)

Pruneri, V.; Margulis, W.; Myrén, N.

2005-01-01

A second-order nonlinearity can be induced in optical fibres through poling. We describe accomplishments of the EU project GLAMOROUS in making low-cost high performance electrooptic and nonlinear optical fibre- and waveguide-based components. In particular a comparison with more traditional...

Targeting Antigens to Dec-205 on Dendritic Cells Induces Immune Protection in Experimental Colitis in Mice

Science.gov (United States)

Wadwa, Munisch; Klopfleisch, Robert; Buer, Jan; Westendorf, Astrid M.

2016-01-01

The endocytotic c-type lectin receptor DEC-205 is highly expressed on immature dendritic cells. In previous studies, it was shown that antigen-targeting to DEC-205 is a useful tool for the induction of antigen-specific Foxp3+ regulatory T cells and thereby can prevent inflammatory processes. However, whether this approach is sufficient to mediate tolerance in mucosal tissues like the gut is unknown. In this study, we established a new mouse model in which the adoptive transfer of naive hemagglutinin (HA)-specific CD4+Foxp3– T cells into VILLIN-HA transgenic mice leads to severe colitis. To analyze if antigen-targeting to DEC-205 could protect against inflammation of the gut, VILLIN-HA transgenic mice were injected with an antibody–antigen complex consisting of the immunogenic HA110–120 peptide coupled to an α-DEC-205 antibody (DEC-HA) before adoptive T cell transfer. DEC-HA-treated mice showed significantly less signs of intestinal inflammation as was demonstrated by reduced loss of body weight and histopathology in the gut. Strikingly, abrogated intestinal inflammation was mediated via the conversion of naive HA-specific CD4+Foxp3– T cells into HA-specific CD4+Foxp3+ regulatory T cells. In this study, we provide evidence that antigen-targeting to DEC-205 can be utilized for the induction of tolerance in mucosal organs that are confronted with large numbers of exogenous antigens. PMID:27141310

Image transport through a disordered optical fibre mediated by transverse Anderson localization

Science.gov (United States)

Karbasi, Salman; Frazier, Ryan J.; Koch, Karl W.; Hawkins, Thomas; Ballato, John; Mafi, Arash

2014-02-01

Transverse Anderson localization of light allows localized optical-beam-transport through a transversely disordered and longitudinally invariant medium. Its successful implementation in disordered optical fibres recently resulted in the propagation of localized beams of radii comparable to that of conventional optical fibres. Here we demonstrate optical image transport using transverse Anderson localization of light. The image transport quality obtained in the polymer disordered optical fibre is comparable to or better than some of the best commercially available multicore image fibres with less pixelation and higher contrast. It is argued that considerable improvement in image transport quality can be obtained in a disordered fibre made from a glass matrix with near wavelength-size randomly distributed air-holes with an air-hole fill-fraction of 50%. Our results open the way to device-level implementation of the transverse Anderson localization of light with potential applications in biological and medical imaging.

Polarisation control of DFB fibre lasers

DEFF Research Database (Denmark)

Varming, Poul; Philipsen, Jacob Lundgreen; Berendt, Martin Ole

1998-01-01

The polarisation properties of a distributed feedback (DFB) fibre laser are investigated. It is shown experimentally that the birefringence of the UV induced phase-shift is the dominating effect controlling the polarisation properties of the laser......The polarisation properties of a distributed feedback (DFB) fibre laser are investigated. It is shown experimentally that the birefringence of the UV induced phase-shift is the dominating effect controlling the polarisation properties of the laser...

Cavitation instabilities between fibres in a metal matrix composite

DEFF Research Database (Denmark)

Tvergaard, Viggo

2016-01-01

induced by bonding to the ceramics that only show elastic deformation. In an MMC the stress state in the metal matrix is highly non-uniform, varying between regions where shear stresses are dominant and regions where hydrostatic tension is strong. An Al–SiC whisker composite with a periodic pattern......Short fibre reinforced metal matrix composites (MMC) are studied here to investigate the possibility that a cavitation instability can develop in the metal matrix. The high stress levels needed for a cavitation instability may occur in metal–ceramic systems due to the constraint on plastic flow...... of transversely staggered fibres is here modelled by using an axisymmetric cell model analysis. First the critical stress level is determined for a cavitation instability in an infinite solid made of the Al matrix material. By studying composites with different distributions and aspect ratios of the fibres...

c-Jun/AP-1 pathway-mediated cyclin D1 expression participates in low dose arsenite-induced transformation in mouse epidermal JB6 Cl41 cells

International Nuclear Information System (INIS)

Zhang Dongyun; Li Jingxia; Gao Jimin; Huang Chuanshu

2009-01-01

Arsenic is a well-documented human carcinogen associated with skin carcinogenesis. Our previous work reveals that arsenite exposure is able to induce cell transformation in mouse epidermal cell JB6 Cl41 through the activation of ERK, rather than JNK pathway. Our current studies further evaluate downstream pathway in low dose arsenite-induced cell transformation in JB6 Cl41 cells. Our results showed that treatment of cells with low dose arsenite induced activation of c-Jun/AP-1 pathway, and ectopic expression of dominant negative mutant of c-Jun (TAM67) blocked arsenite-induced transformation. Furthermore, our data indicated that cyclin D1 was an important downstream molecule involved in c-Jun/AP-1-mediated cell transformation upon low dose arsenite exposure, because inhibition of cyclin D1 expression by its specific siRNA in the JB6 Cl41 cells resulted in impairment of anchorage-independent growth of cells induced by low dose arsenite. Collectively, our results demonstrate that c-Jun/AP-1-mediated cyclin D1 expression is at least one of the key events implicated in cell transformation upon low dose arsenite exposure

Quinacrine induces apoptosis in human leukemia K562 cells via p38 MAPK-elicited BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression

International Nuclear Information System (INIS)

Changchien, Jung-Jung; Chen, Ying-Jung; Huang, Chia-Hui; Cheng, Tian-Lu; Lin, Shinne-Ren; Chang, Long-Sen

2015-01-01

Although previous studies have revealed the anti-cancer activity of quinacrine, its effect on leukemia is not clearly resolved. We sought to explore the cytotoxic effect and mechanism of quinacrine action in human leukemia K562 cells. Quinacrine induced K562 cell apoptosis accompanied with ROS generation, mitochondrial depolarization, and down-regulation of BCL2L1 and BCL2. Upon exposure to quinacrine, ROS-mediated p38 MAPK activation and ERK inactivation were observed in K562 cells. Quinacrine-induced cell death and mitochondrial depolarization were suppressed by the p38MAPK inhibitor SB202190 and constitutively active MEK1 over-expression. Activation of p38 MAPK was shown to promote BCL2 degradation. Further, ERK inactivation suppressed c-Jun-mediated transcriptional expression of BCL2L1. Over-expression of BCL2L1 and BCL2 attenuated quinacrine-evoked mitochondrial depolarization and rescued the viability of quinacrine-treated cells. Taken together, our data indicate that quinacrine-induced K562 cell apoptosis is mediated through mitochondrial alterations triggered by p38 MAPK-mediated BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression. - Highlights: • Quinacrine induces K562 cell apoptosis via down-regulation of BCL2 and BCL2L1. • Quinacrine induces p38 MAPK activation and ERK inactivation in K562 cells. • Quinacrine elicits p38 MAPK-mediated BCL2 down-regulation. • Quinacrine suppresses ERK/c-Jun-mediated BCL2L1 expression

Inhibition of glycolipid biosynthesis by N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin protects against the inflammatory response in hapten-induced colitis

NARCIS (Netherlands)

Shen, Chong; Bullens, Dominique; Kasran, Ahmad; Maerten, Philippe; Boon, Louis; Aerts, Johannes M. F. G.; van Assche, Gert; Geboes, Karel; Rutgeerts, Paul; Ceuppens, Jan L.

2004-01-01

Since glycolipid biosynthesis is potentially involved in immunological and inflammatory responses, we tested the effect of a novel inhibitor of intracellular glycolipid biosynthesis N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin (AMP-DNM) in two hapten-induced colitis models: trinitrobenzene

Crack Growth Monitoring by Embedded Optical Fibre Bragg Grating Sensors: Fibre Reinforced Plastic Crack Growing Detection

DEFF Research Database (Denmark)

Pereira, Gilmar Ferreira; Mikkelsen, Lars Pilgaard; McGugan, Malcolm

2015-01-01

This article presents a novel method to asses a crack growing/damage event in fibre reinforced plastic, or adhesive using Fibre Bragg Grating (FBG) sensors embedded in a host material. Different features of the crack mechanism that induce a change in the FBG response were identified. Double Canti...

[Allergic colitis in exclusively breast-fed infants].

Science.gov (United States)

Sierra Salinas, C; Blasco Alonso, J; Olivares Sánchez, L; Barco Gálvez, A; del Río Mapelli, L

2006-02-01

Eosinophilic colitis is induced by antigens present in cow's milk proteins in formula or human milk. In the last few years, an increasing number of cases have been diagnosed in exclusively breast-fed infants. We performed a retrospective study of 13 infants diagnosed with allergic colitis in our unit between January 1997 and January 2004. All the infants had been exclusively breast-fed. In all patients, initial symptoms were digestive (12 with mucus and bloody stools). Onset of symptoms occurred at 0-3 months in 77 %. Laboratory data of the allergic compound were negative. The main locations were the descending and sigmoid colon (75 %). Biopsy demonstrated acute inflammation, with neutrophil infiltration and an increase in eosinophils. In all patients, initial treatment consisted of exclusion of cow's milk proteins from the mother's diet. Ten of the 13 patients showed no improvement, requiring exclusive administration of protein-free hydrolyzate. In 3 infants, breastfeeding was maintained (breastfeeding without cow's milk proteins plus hydrolyzate). Diagnosis of eosinophilic colitis is based on exclusion of other causes of specific colitis and typical endoscopic and ultrastructural findings. Moreover, a satisfactory response to dietary treatment must be demonstrated. This diagnosis should be considered in breast-fed infants with rectal bleeding without involvement of general health status.

Divergent Roles of Interferon-γ and Innate Lymphoid Cells in Innate and Adaptive Immune Cell-Mediated Intestinal Inflammation.

Science.gov (United States)

Brasseit, Jennifer; Kwong Chung, Cheong K C; Noti, Mario; Zysset, Daniel; Hoheisel-Dickgreber, Nina; Genitsch, Vera; Corazza, Nadia; Mueller, Christoph

2018-01-01

Aberrant interferon gamma (IFNγ) expression is associated with the pathogenesis of numerous autoimmune- and inflammatory disorders, including inflammatory bowel diseases (IBD). However, the requirement of IFNγ for the pathogenesis of chronic intestinal inflammation remains controversial. The aim of this study was thus to investigate the role of IFNγ in experimental mouse models of innate and adaptive immune cell-mediated intestinal inflammation using genetically and microbiota-stabilized hosts. While we find that IFNγ drives acute intestinal inflammation in the anti-CD40 colitis model in an innate lymphoid cell (ILC)-dependent manner, IFNγ secreted by both transferred CD4 T cells and/or cells of the lymphopenic Rag1 -/- recipient mice was dispensable for CD4 T cell-mediated colitis. In the absence of IFNγ, intestinal inflammation in CD4 T cell recipient mice was associated with enhanced IL17 responses; consequently, targeting IL17 signaling in IFNγ-deficient mice reduced T cell-mediated colitis. Intriguingly, in contrast to the anti-CD40 model of colitis, depletion of ILC in the Rag1 -/- recipients of colitogenic CD4 T cells did not prevent induction of colonic inflammation. Together, our findings demonstrate that IFNγ represents an essential, or a redundant, pro-inflammatory cytokine for the induction of intestinal inflammation, depending on the experimental mouse model used and on the nature of the critical disease inducing immune cell populations involved.

Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis.

Science.gov (United States)

Ha, Christina; Kornbluth, Asher

2014-12-01

The management of Crohn's disease and ulcerative colitis has become increasingly complex. With the current utilization of immunosuppressive therapies earlier in the disease course for patients presenting with moderate to severe disease, there is a great need for additional biologic agents targeting inflammatory mediators other than anti-tumor necrosis factor-α (anti-TNF) agents. Although anti-TNF agents have positively impacted the treatment of inflammatory bowel disease, many patients can lose their response or develop intolerance to these agents over time through the formation of antidrug antibodies. Furthermore, a sizeable percentage of patients are primary nonresponders to anti-TNF drugs. Vedolizumab (Entyvio, Takeda Pharmaceuticals), a monoclonal antibody to the α4β7 integrin, inhibits gut lymphocyte trafficking and has been demonstrated to be an effective and safe agent for the treatment of both Crohn's disease and ulcerative colitis. This article reviews the clinical trial evidence and rationale for the use of vedolizumab in moderate to severe Crohn's disease and ulcerative colitis.

Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis.

Science.gov (United States)

Harris, Nicholas; Koppel, Juraj; Zsila, Ferenc; Juhas, Stefan; Il'kova, Gabriela; Kogan, Faina Yurgenzon; Lahmy, Orly; Wildbaum, Gizi; Karin, Nathan; Zhuk, Regina; Gregor, Paul

2016-04-01

Elucidate the mechanism of action of the small molecule inhibitor of protein binding to glycosaminoglycans, RX-111 and assay its anti-inflammatory activity in animal models of inflammatory disease. The glycosaminoglycan, heparin, was used in the mechanism of action study of RX-111. Human T lymphocytes and umbilical vein endothelial cells were used to assay the in vitro activity of RX-111. Mouse and rat models of disease were used to assay the anti-inflammatory activity of RX-111 in vivo. Circular dichroism and UV/Vis absorption spectroscopy were used to study the binding of RX-111 to the glycosaminoglycan, heparin. T lymphocyte rolling on endothelial cells under shear flow was used to assay RX-111 activity in vitro. Delayed-type hypersensitivity (DTH) and tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in mice and experimental autoimmune encephalomyelitis (EAE) in rats were used to assay anti-inflammatory activity of RX-111 in vivo. RX-111 was shown to bind directly to heparin. It inhibited leukocyte rolling on endothelial cells under shear flow and reduced inflammation in the mouse model of DTH. RX-111 was efficacious in the mouse model of inflammatory bowel disease, TNBS-induced colitis and the rat model of multiple sclerosis, EAE. RX-111 exercises its broad spectrum anti-inflammatory activity by a singular mechanism of action, inhibition of protein binding to the cell surface GAG, heparan sulfate. RX-111 and related thieno[2,3-c]pyridine derivatives are potential therapeutics for the treatment of inflammatory and autoimmune diseases.

Prostaglandin E2 Activates YAP and a Positive-Signaling Loop to Promote Colon Regeneration After Colitis but Also Carcinogenesis in Mice.

Science.gov (United States)

Kim, Han-Byul; Kim, Minchul; Park, Young-Soo; Park, Intae; Kim, Tackhoon; Yang, Sung-Yeun; Cho, Charles J; Hwang, DaeHee; Jung, Jin-Hak; Markowitz, Sanford D; Hwang, Sung Wook; Yang, Suk-Kyun; Lim, Dae-Sik; Myung, Seung-Jae

2017-02-01

Prostaglandin E 2 (PGE 2 ) is mediator of inflammation that regulates tissue regeneration, but its continual activation has been associated with carcinogenesis. Little is known about factors in the PGE 2 signaling pathway that contribute to tumor formation. We investigated whether yes-associated protein 1 (YAP1), a transcriptional co-activator in the Hippo signaling pathway, mediates PGE 2 function. DLD-1 and SW480 colon cancer cell lines were transfected with vectors expressing transgenes or small hairpin RNAs and incubated with recombinant PGE 2 , with or without pharmacologic inhibitors of signaling proteins, and analyzed by immunoblot, immunofluorescence, quantitative reverse-transcription polymerase chain reaction, transcriptional reporter, and proliferation assays. Dextran sodium sulfate (DSS) was given to induce colitis in C57/BL6 (control) mice, as well as in mice with disruption of the hydroxyprostaglandin dehydrogenase 15 gene (15-PGDH-knockout mice), Yap1 gene (YAP-knockout mice), and double-knockout mice. Some mice also were given indomethacin to block PGE 2 synthesis. 15-PGDH knockout mice were crossed with mice with intestine-specific disruption of the salvador family WW domain containing 1 gene (Sav1), which encodes an activator of Hippo signaling. We performed immunohistochemical analyses of colon biopsy samples from 26 patients with colitis-associated cancer and 51 age-and sex-matched patients with colorectal cancer (without colitis). Incubation of colon cancer cell lines with PGE 2 led to phosphorylation of cyclic adenosine monophosphate-responsive element binding protein 1 and increased levels of YAP1 messenger RNA, protein, and YAP1 transcriptional activity. This led to increased transcription of the prostaglandin-endoperoxide synthase 2 gene (PTGS2 or cyclooxygenase 2) and prostaglandin E-receptor 4 gene (PTGER4 or EP4). Incubation with PGE 2 promoted proliferation of colon cancer cell lines, but not cells with knockdown of YAP1. Control mice

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.

Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid-induced colitis in the rat.

Science.gov (United States)

Miampamba, M; Parr, E J; McCafferty, D M; Wallace, J L; Sharkey, K A

1998-03-01

We investigated the effects of benzalkonium chloride (BAC) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. TNBS was administered intrarectally before and/or after BAC treatment. In the first study, the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the second study, animals were treated with BAC before, after or before and after TNBS, and were examined 7 days later. The severity of colitis was assessed by macroscopic and histological scoring of the colonic damage and by determination of colonic myeloperoxidase (MPO) activity. Macrophages and CD4+ and CD8+ T cells were examined by immunohistochemistry. When BAC was instilled into the colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological features of the colon were similar to that of controls (TNBS alone). In contrast, MPO activity was significantly reduced in all three groups post-treated with BAC. In the groups examined 7 days after TNBS treatment, rats post-treated with BAC exhibited increased weight gain and significantly reduced macroscopic damage and MPO activity compared to the TNBS control group. Rats pre-treated with BAC exhibited less macroscopic damage of the colon than rats receiving only TNBS, but histological damage, MPO and weight gain were unchanged from TNBS controls. Immunohistochemistry revealed that BAC pre-treatment increased the numbers of macrophages and T cells in the colon. After TNBS treatment, macrophage accumulation was evident in the colon, but T cells were scarce. However, these cells were preserved or enhanced in the colonic mucosa in TNBS-treated rats that had been pre-treated with BAC. Treatment with BAC, particularly after induction of colitis, produces a significant reduction in the severity of tissue injury and inflammation through mechanisms that are not fully understood.

Colitis of Behcet's syndrome

International Nuclear Information System (INIS)

O'Connell, D.J.; Courtney, J.V.; Riddell, R.H.

1980-01-01

Three patients with Behcet's syndrome and colitis are described. The radiologic and histologic appearances of the colitis are discussed. The similarities of Behcet's colitis to Crohn's disease are outlined. The cases demonstrate the necessity to consider Behcet's syndrome in the differential diagnosis of inflammatory bowel disease. (orig.) [de

Surface treated polypropylene (PP) fibres for reinforced concrete

Energy Technology Data Exchange (ETDEWEB)

López-Buendía, Angel M., E-mail: buendia@uv.es [AIDICO Technological Institute of Construction, Benjamin Franklin 17, 46380 Paterna, Valencia (Spain); Romero-Sánchez, María Dolores [AIDICO Technological Institute of Construction, Marble Technical Unit, Camí de Castella 4, 03660 Novelda. Alicante (Spain); Climent, Verónica [Lafarge Cementos, Polígono Sepes, Isaac Newton s/n, 46500 Sagunto, Valencia (Spain); Guillem, Celia [AIDICO Technological Institute of Construction, Marble Technical Unit, Camí de Castella 4, 03660 Novelda. Alicante (Spain)

2013-12-15

Surface treatments on a polypropylene (PP) fibre have contributed to the improvement of fibre/concrete adhesion in fibre-reinforced concrete. The treatments to the PP fibre were characterized by contact angle measurements, ATR-IR and XPS to analyse chemical alterations. The surface topography and fibre/concrete interaction were analysed by several microscopic techniques, namely optical petrographic, and scanning electron microscopy. Treatment modified the surface chemistry and topography of the fibre by introducing sodium moieties and created additional fibre surface roughness. Modifications in the fibre surface led to an increase in the adhesion properties between the treated fibres and concrete and an improvement in the mechanical properties of the fibre-reinforced concrete composite as compared to the concrete containing untreated PP fibres. Compatibility with the concrete and increased roughness and mineral surface was also improved by nucleated portlandite and ettringite mineral association anchored on the alkaline PP fibre surface, which is induced during treatment.

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

Directory of Open Access Journals (Sweden)

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.

Disseminated refractory pyoderma gangraenosum during an ulcerative colitis flare. Treatment with infliximab.

Science.gov (United States)

Zampeli, Vasiliki A; Lippert, Undine; Nikolakis, Georgios; Makrantonaki, Evgenia; Tzellos, Thrasivoulos G; Krause, Ulf; Zouboulis, Christos C

2015-09-30

Pyoderma gangraenosum is an immune-mediated, inflammatory, neutrophilic dermatosis of unknown etiology, which represents one of the extraintestinal manifestations of inflammatory bowel disease. It is a rare disease that occurs in less than 1% of patients with inflammatory bowel disease and with the same ratio in patients with Crohn's disease and ulcerative colitis. A 36-year-old woman was diagnosed with ulcerative colitis 6 years before admission to our dermatology department with an acute disseminated pyoderma gangraenosum with mucosal involvement, during a flare of ulcerative colitis. Disease progression was interrupted by intravenous administration of the tumor necrosis factor-α inhibitor infliximab at 5 mg/kg at weeks 0, 2, and 6 (1st cycle) and every 8 weeks thereafter. Improvement of intestinal, skin and oral manifestations was evident already after the 1st cycle of treatment and has been maintained since (at least 16 months). This case report is one of very few on disseminated pyoderma gangraenosum with oral involvement complicating ulcerative colitis, where infliximab was shown to have a rapid efficacy on skin, mucosal and bowel symptoms.

IP3-dependent intracellular Ca2+ release is required for cAMP-induced c-fos expression in hippocampal neurons

International Nuclear Information System (INIS)

Zhang, Wenting; Tingare, Asmita; Ng, David Chi-Heng; Johnson, Hong W.; Schell, Michael J.; Lord, Rebecca L.; Chawla, Sangeeta

2012-01-01

Highlights: ► cAMP-induced c-fos expression in hippocampal neurons requires a submembraneous Ca 2+ pool. ► The submembraneous Ca 2+ pool derives from intracellular ER stores. ► Expression of IP 3 -metabolizing enzymes inhibits cAMP-induced c-fos expression. ► SRE-mediated and CRE-mediated gene expression is sensitive to IP 3 -metabolizing enzymes. ► Intracellular Ca 2+ release is required for cAMP-induced nuclear translocation of TORC1. -- Abstract: Ca 2+ and cAMP are widely used in concert by neurons to relay signals from the synapse to the nucleus, where synaptic activity modulates gene expression required for synaptic plasticity. Neurons utilize different transcriptional regulators to integrate information encoded in the spatiotemporal dynamics and magnitude of Ca 2+ and cAMP signals, including some that are Ca 2+ -responsive, some that are cAMP-responsive and some that detect coincident Ca 2+ and cAMP signals. Because Ca 2+ and cAMP can influence each other’s amplitude and spatiotemporal characteristics, we investigated how cAMP acts to regulate gene expression when increases in intracellular Ca 2+ are buffered. We show here that cAMP-mobilizing stimuli are unable to induce expression of the immediate early gene c-fos in hippocampal neurons in the presence of the intracellular Ca 2+ buffer BAPTA-AM. Expression of enzymes that attenuate intracellular IP 3 levels also inhibited cAMP-dependent c-fos induction. Synaptic activity induces c-fos transcription through two cis regulatory DNA elements – the CRE and the SRE. We show here that in response to cAMP both CRE-mediated and SRE-mediated induction of a luciferase reporter gene is attenuated by IP 3 metabolizing enzymes. Furthermore, cAMP-induced nuclear translocation of the CREB coactivator TORC1 was inhibited by depletion of intracellular Ca 2+ stores. Our data indicate that Ca 2+ release from IP 3 -sensitive pools is required for cAMP-induced transcription in hippocampal neurons.

Anti-inflammatory effects of Mangifera indica L. extract in a model of colitis

Science.gov (United States)

Márquez, Lucía; Pérez-Nievas, Beatriz G; Gárate, Icíar; García-Bueno, Borja; Madrigal, José LM; Menchén, Luis; Garrido, Gabino; Leza, Juan C

2010-01-01

AIM: To investigate the effect of aqueous extract from Mangifera indica L. (MIE) on dextran sulfate sodium (DSS)-induced colitis in rats. METHODS: MIE (150 mg/kg) was administered in two different protocols: (1) rectally, over 7 d at the same time as DSS administration; and (2) once daily over 14 d (by oral gavage, 7 d before starting DSS, and rectally for 7 d during DSS administration). General observations of clinical signs were performed. Anti-inflammatory activity of MIE was assessed by myeloperoxidase (MPO) activity. Colonic lipid peroxidation was determined by measuring the levels of thiobarbituric acid reactive substances (TBARS). Reduced glutathione (GSH) levels, expression of inflammatory related mediators [inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, respectively] and cytokines [tumor necrosis factor (TNF)-α and TNF receptors 1 and 2] in colonic tissue were also assessed. Interleukin (IL)-6 and TNF-α serum levels were also measured. RESULTS: The results demonstrated that MIE has anti-inflammatory properties by improvement of clinical signs, reduction of ulceration and reduced MPO activity when administered before DSS. In addition, administration of MIE for 14 d resulted in an increase in GSH and reduction of TBARS levels and iNOS, COX-2, TNF-α and TNF R-2 expression in colonic tissue, and a decrease in IL-6 and TNF-α serum levels. CONCLUSION: MIE has anti-inflammatory activity in a DSS-induced rat colitis model and preventive administration (prior to DSS) seems to be a more effective protocol. PMID:20954278

Cyclic ADP-ribose and IP3 mediate abscisic acid-induced isoflavone accumulation in soybean sprouts

International Nuclear Information System (INIS)

Jiao, Caifeng; Yang, Runqiang; Gu, Zhenxin

2016-01-01

In this study, the roles of ABA-cADPR-Ca 2+ and ABA-IP3-Ca 2+ signaling pathways in UV-B-induced isoflavone accumulation in soybean sprouts were investigated. Results showed that abscisic acid (ABA) up regulated cyclic ADP-ribose (cADPR) and inositol 1,4,5-trisphosphate (IP3) levels in soybean sprouts under UV-B radiation. Furthermore, cADPR and IP3, as second messengers of UV-B-triggered ABA, induced isoflavone accumulation by up-regulating proteins and genes expression and activity of isoflavone biosynthetic-enzymes (chalcone synthase, CHS; isoflavone synthase, IFS). After Ca 2+ was chelated by EGTA, isoflavone content decreased. Overall, ABA-induced cADPR and IP3 up regulated isoflavone accumulation which was mediated by Ca 2+ signaling via enhancing the expression of proteins and genes participating in isoflavone biosynthesis in soybean sprouts under UV-B radiation. - Highlights: • UV-B-induced cADPR and IP3 synthesis was mediated by ABA. • cADPR and IP3 were involved in UV-B-ABA-induced isoflavone accumulation. • cADPR and IP3-induced isoflavone accumulation may be mediated by Ca 2+ . • ABA, cADPR, IP3 and Ca 2+ could activate proteins expression of CHS and IFS.

Functional effects of the DCM mutant Gly159Asp troponin C in skinned muscle fibres

DEFF Research Database (Denmark)

Preston, Laura C; Lipscomb, Simon; Robinson, Paul

2006-01-01

We recently reported a dilated cardiomyopathy (DCM) causing mutation in a novel disease gene, TNNC1, which encodes cardiac troponin C (TnC). We have determined how this mutation, Gly159Asp, affects contractile regulation when incorporated into muscle fibres. Endogenous troponin in rabbit skinned...

FibreBags vs. FibreCaps for acid and neutral detergent fibre analysis

OpenAIRE

Koivisto , Jason

2003-01-01

International audience; A new procedure for determining acid detergent fibre and neutral detergent fibre (ADF and NDF) was developed to reduce the need for filtration and to allow for batch processing of forage samples. The FibreBag system is an economically necessary evolution of the earlier FibreCap system. The purpose of this enquiry was to determine if the FibreBag is a suitable replacement for the FibreCap. The FibreBag method produced very similar results to the FibreCap system of analy...

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

Science.gov (United States)

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

2015-12-30

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. This study aims to isolate and characterise guinea pig MSCs and then test their therapeutic potential for the treatment of enteric neuropathy associated with intestinal inflammation. MSCs from guinea pig bone marrow and adipose tissue were isolated and characterised in vitro. In in vivo experiments, guinea pigs received either TNBS for the induction of colitis or sham treatment by enema. MSCs were administered at a dose of 1 × 10(6) cells via enema 3 h after the induction of colitis. Colon tissues were collected 24 and 72 h after TNBS administration to assess the level of inflammation and damage to the ENS. The secretion of transforming growth factor-β1 (TGF-β1) was analysed in MSC conditioned medium by flow cytometry. Cells isolated from both sources were adherent to plastic, multipotent and expressed some human MSC surface markers. In vitro characterisation revealed distinct differences in growth kinetics, clonogenicity and cell morphology between MSC types. In an in vivo model of TNBS-induced colitis, guinea pig bone marrow MSCs were comparatively more efficacious than adipose tissue MSCs in attenuating weight loss, colonic tissue damage and leukocyte infiltration into the mucosa and myenteric plexus. MSCs from both sources were equally neuroprotective in the amelioration of enteric neuronal loss and changes to the neurochemical coding of neuronal subpopulations. MSCs from both sources secreted TGF-β1 which exerted neuroprotective effects in vitro. This study is the first

Electrical stimulation to the trigeminal proprioceptive fibres that innervate the mechanoreceptors in Müller's muscle induces involuntary reflex contraction of the frontalis muscles.

Science.gov (United States)

Matsuo, Kiyoshi; Osada, Yoshiro; Ban, Ryokuya

2013-02-01

The levator and frontalis muscles lack interior muscle spindles, despite consisting of slow-twitch fibres that involuntarily sustain eyelid-opening and eyebrow-raising against gravity. To compensate for this anatomical defect, this study hypothetically proposes that initial voluntary contraction of the levator fast-twitch muscle fibres stretches the mechanoreceptors in Müller's muscle and evokes proprioception, which continuously induces reflex contraction of slow-twitch fibres of the levator and frontalis muscles. This study sought to determine whether unilateral transcutaneous electrical stimulation to the trigeminal proprioceptive fibres that innervate the mechanoreceptors in Müller's muscle could induce electromyographic responses in the frontalis muscles, with monitoring responses in the orbicularis oculi muscles. The study population included 27 normal subjects and 23 subjects with aponeurotic blepharoptosis, who displayed persistently raised eyebrows on primary gaze and light eyelid closure. The stimulation induced a short-latency response in the ipsilateral frontalis muscle of all subjects and long-latency responses in the bilateral frontalis muscles of normal subjects. However, it did not induce long-latency responses in the bilateral frontalis muscles of subjects with aponeurotic blepharoptosis. The orbicularis oculi muscles showed R1 and/or R2 responses. The stimulation might reach not only the proprioceptive fibres, but also other sensory fibres related to the blink or corneal reflex. The experimental system can provoke a monosynaptic short-latency response in the ipsilateral frontalis muscle, probably through the mesencephalic trigeminal proprioceptive neuron and the frontalis motor neuron, and polysynaptic long-latency responses in the bilateral frontalis muscles through an unknown pathway. The latter neural circuit appeared to be engaged by the circumstances of aponeurotic blepharoptosis.

FolC2-mediated folate metabolism contributes to suppression of inflammation by probiotic Lactobacillus reuteri.

Science.gov (United States)

Thomas, Carissa M; Saulnier, Delphine M A; Spinler, Jennifer K; Hemarajata, Peera; Gao, Chunxu; Jones, Sara E; Grimm, Ashley; Balderas, Miriam A; Burstein, Matthew D; Morra, Christina; Roeth, Daniel; Kalkum, Markus; Versalovic, James

2016-10-01

Bacterial-derived compounds from the intestinal microbiome modulate host mucosal immunity. Identification and mechanistic studies of these compounds provide insights into host-microbial mutualism. Specific Lactobacillus reuteri strains suppress production of the proinflammatory cytokine, tumor necrosis factor (TNF), and are protective in a mouse model of colitis. Human-derived L. reuteri strain ATCC PTA 6475 suppresses intestinal inflammation and produces 5,10-methenyltetrahydrofolic acid polyglutamates. Insertional mutagenesis identified the bifunctional dihydrofolate synthase/folylpolyglutamate synthase type 2 (folC2) gene as essential for 5,10-methenyltetrahydrofolic acid polyglutamate biosynthesis, as well as for suppression of TNF production by activated human monocytes, and for the anti-inflammatory effect of L. reuteri 6475 in a trinitrobenzene sulfonic acid-induced mouse model of acute colitis. In contrast, folC encodes the enzyme responsible for folate polyglutamylation but does not impact TNF suppression by L. reuteri. Comparative transcriptomics between wild-type and mutant L. reuteri strains revealed additional genes involved in immunomodulation, including previously identified hdc genes involved in histidine to histamine conversion. The folC2 mutant yielded diminished hdc gene cluster expression and diminished histamine production, suggesting a link between folate and histadine/histamine metabolism. The identification of genes and gene networks regulating production of bacterial-derived immunoregulatory molecules may lead to improved anti-inflammatory strategies for digestive diseases. © 2016 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

[TRPM8 mediates PC-12 neuronal cell apoptosis induced by oxygen-glucose deprivation through cAMP-PKA/UCP4 signaling].

Science.gov (United States)

Li, Hong-Wei; Zhou, Bin; Zhang, Hai-Hong

2016-08-20

To explore the molecular mechanism responsible for apoptosis of PC-12 neuronal cells induced by oxygen-glucose deprivation (OGD). PC12 cells were exposed to OGD for 24 h to simulate ischemia-reperfusion injury. Flow cytometry was employed detect the cell apoptosis, and the expresions of TRPM8, UCP4, cAMP and PKA in the exposed cells were detected with RT-PCR and Western blotting. The changes in the expressions of Bax, Bcl-2, cAMP, PKA and UCP4 proteins were detected in the exposed cells in resposne to inhibition of TRPM8 and cAMP-PKA signal or over-expression of UCP4. OGD for 24 induced obvious apoptosis in PC-12 cells and caused TRPM8 over-expression and inhibition of UCP4 and cAMP-PKA signaling. Inhibiting TRPM8 expression reduced the cell apoptosis and up-regulated cAMP, p-PKA and UCP4 in the cells exposed to OGD. In cells exposed to OGD, inhibition of TRPM8 and cAMP-PKA signaling suppressed the expressio of UCP4 and increased the cell apoptosis. TRPM8 mediates OGD-induced PC12 cell apoptosis through cAMP-PKA/UCP4 signaling.

Direct and Indirect Effects of Tofacitinib on Treatment Satisfaction in Patients with Ulcerative Colitis.

Science.gov (United States)

Panés, Julian; Su, Chinyu; Bushmakin, Andrew G; Cappelleri, Joseph C; Healey, Paul

2016-11-01

This mediation modelling analysis evaluated direct and indirect effects of tofacitinib, an oral, small molecule Janus kinase inhibitor under investigation for ulcerative colitis, on patient treatment satisfaction. Data from an 8-week randomized Phase 2 trial [NCT00787202] in adults with moderate-to-severe, active ulcerative colitis receiving twice-daily tofacitinib 0.5-15mg [n=146] or placebo [n=48] were analysed in patient-reported [n=149] and clinician-reported [n=170] outcomes-based mediation models. Binary predictor variable: Treatment [pooled active treatment vs placebo]. Eventual dependent variable: Week 8 patient treatment satisfaction [measured on a five-point Likert scale]. Mediators of treatment effect on satisfaction: Week 8 Inflammatory Bowel Disease Questionnaire domains [Bowel Symptoms, Emotional Health, Social Function and Systemic Symptoms] and Mayo scale domains [Stool Frequency, Rectal Bleeding, Physician's Global Assessment and Endoscopic Disease Activity] for patient-reported and clinician-reported models, respectively. Overall tofacitinib indirect effect on satisfaction via Inflammatory Bowel Disease Questionnaire domains was 40.5% [ptofacitinib effect on satisfaction, 32.4% [p=0.05] was indirectly mediated via Bowel Symptoms; and 30.0% [p=0.04] via Stool Frequency. In total, 59.5% [ptofacitinib's effect on satisfaction was unrelated to Inflammatory Bowel Disease Questionnaire and Mayo scale domains in the patient-reported and clinician-reported models, respectively. Bowel function is an important factor for patient treatment satisfaction with tofacitinib. Treatment effect on patient satisfaction was almost completely mediated via improvement in Mayo scale domains. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Glass fibre sensors for medical applications - fibre-optical dosimeter system. Cooperation project 1991-1994. Final report

International Nuclear Information System (INIS)

1996-01-01

The final report summarizes the results of a cooperation project on the applications of fibre-optical sensors in medical technology. The FADOS dosimeter system is presented which comprises an implantable glass fibre dosimeter. It can be applied in radiotherapy for online dose metering directly at the tumour or in the surrounding healthy tissue. The dosimeter is placed in a tissue-compatible flexible catheter tube and remains inside the body during the radiotherapy treatiment. The measuring principle is based on the effect of radiation-induced damping inside a glass fibre. (DG) [de

Vedolizumab as a Treatment for Crohn’s Disease and Ulcerative Colitis

Science.gov (United States)

Ha, Christina

2014-01-01

The management of Crohn’s disease and ulcerative colitis has become increasingly complex. With the current utilization of immunosuppressive therapies earlier in the disease course for patients presenting with moderate to severe disease, there is a great need for additional biologic agents targeting inflammatory mediators other than anti-tumor necrosis factor-α (anti-TNF) agents. Although anti-TNF agents have positively impacted the treatment of inflammatory bowel disease, many patients can lose their response or develop intolerance to these agents over time through the formation of antidrug antibodies. Furthermore, a sizeable percentage of patients are primary nonresponders to anti-TNF drugs. Vedolizumab (Entyvio, Takeda Pharmaceuticals), a monoclonal antibody to the α4β7 integrin, inhibits gut lymphocyte trafficking and has been demonstrated to be an effective and safe agent for the treatment of both Crohn’s disease and ulcerative colitis. This article reviews the clinical trial evidence and rationale for the use of vedolizumab in moderate to severe Crohn’s disease and ulcerative colitis. PMID:27524947

Life cycle strain monitoring in glass fibre reinforced polymer laminates using embedded fibre Bragg grating sensors from manufacturing to failure

DEFF Research Database (Denmark)

Nielsen, Michael Wenani; Schmidt, Jacob Wittrup; Høgh, Jacob Herold

2013-01-01

A holistic approach to strain monitoring in fibre-reinforced polymer composites is presented using embedded fibre Bragg grating sensors. Internal strains are monitored in unidirectional E-glass/epoxy laminate beams during vacuum infusion, curing, post-curing and subsequent loading in flexure until...... of the different cure temperatures and tool/part interfaces used. Substantial internal process-induced strains develop in the transverse fibre direction, which should be taken into consideration when designing fibre-reinforced polymer laminates. Flexure tests indicate no significant difference in the mechanical...

Green tea polyphenols and sulfasalazine have parallel anti-inflammatory properties in colitis models

Directory of Open Access Journals (Sweden)

Helieh S Oz

2013-06-01

Full Text Available Background: There is no cure for autoimmune chronic inflammatory bowel disease (IBD. IBD patients commonly use complementary and alternative medications of which the safety, efficacy and interaction with standard-of-care therapies are not fully known. Thus the consequences can become life-threatening. Sulfasalazine commonly used in IBD, potentially has severe adverse effects, including infertility, pulmonary fibrosis, lack of response and ultimately patients may require intestinal resection. We hypothesized that green tea polyphenols (GrTP, EGCG and sulfasalazine have similar anti-inflammatory properties. Methods: BALB/c mice received Dextran sodium sulfate (DSS to induce colitis (ulcerative colitis model. Exposure of IL-10 deficient mice (BALB/c-background to normal microbiota provoked enterocolitis (mimics Crohn’s disease. Animals were treated with agents incorporated into daily diets. Control animals received sham treatment. Results: DSS-treated animals developed severe bloody diarrhea and colitis (score 0-4, 3.2+0.27. IL-10 deficient mice developed severe enterocolitis as manifested by diarrhea, rectal prolapse and colonic lesions. Animals tolerated regimens (GrTP, EGCG, sulfasalazine with no major side effects, and further developed less severe colitis/enterocolitis. GrTP, EGCG and sulfasalazine significantly ameliorated colonic damage and histological scores in treated animals in a similar manner (GrTP vs DSS p<0.05; EGCG, sulfasalazine vs DSS p<0.01. The inflammatory markers TNFα (3-fold, IL-6 (14-fold and serum amyloid A (40-fold increased in colitic animals and significantly decreased with treatment regiments. In contrast, circulatory leptin levels decreased in colitic animals (2-fold. EGCG additionally reduced leptin levels (p<0.01 while GrTP and sulfasalazine had no effect on leptin levels (p<0.05. Hepatic and colonic antioxidants were significantly depleted in colitic animals and treatment regiments significantly restored

Involvement of IRF4 dependent dendritic cells in T cell dependent colitis

DEFF Research Database (Denmark)

Pool, Lieneke; Rivollier, Aymeric Marie Christian; Agace, William Winston

in genetically susceptible individuals and pathogenic CD4+ T cells, which accumulate in the inflamed mucosa, are believed to be key drivers of the disease. While dendritic cells (DCs) are important in the priming of intestinal adaptive immunity and tolerance their role in the initiation and perpetuation...... of chronic intestinal inflammation remains unclear. In the current study we used the CD45RBhi T cell transfer model of colitis to determine the role of IRF4 dependent DCs in intestinal inflammation. In this model naïve CD4+ T cells when transferred into RAG-/- mice, proliferate and expand in response...... to bacterial derived luminal antigen, localize to the intestinal mucosa and induce colitis. Adoptive transfer of naïve T cells into CD11cCre.IRF4fl/fl.RAG-1-/- mice resulted in reduced monocyte recruitment to the intestine and mesenteric lymph nodes (MLN) compared to Cre- controls. Inflammatory cytokines...

GL-V9, a new synthetic flavonoid derivative, ameliorates DSS-induced colitis against oxidative stress by up-regulating Trx-1 expression via activation of AMPK/FOXO3a pathway.

Science.gov (United States)

Zhao, Yue; Sun, Yang; Ding, Youxiang; Wang, Xiaoping; Zhou, Yuxin; Li, Wenjun; Huang, Shaoliang; Li, Zhiyu; Kong, Lingyi; Guo, Qinglong; Lu, Na

2015-09-22

GL-V9, a new synthesized flavonoid derivative, has been reported to possess anti-cancer properties in our previous studies. Uncontrolled overproduction of reactive oxygen species (ROS) has been implicated in oxidative damage of inflammatory bowel disease (IBD). In this study, we aimed to investigate the protective effect of GL-V9 against dextran sulfate sodium (DSS)-induced colitis. GL-V9 attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. GL-V9 also inhibited inflammatory cells infiltration and decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities. Moreover, GL-V9 inhibited ROS and malondialdehyde (MDA) generation, but enhanced superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity. GL-V9 reduced pro-inflammatory cytokines production in serum and colon as well. Mechanically, GL-V9 could increase Trx-1 via activation of AMPK/FOXO3a to suppress DSS-induced colonic oxidative stress. Furthermore, GL-V9 decreased pro-inflammatory cytokines and ROS production and increased the antioxidant defenses in the mouse macrophage cells RAW264.7 by promoting Trx-1 expression. In conclusion, our study demonstrated that GL-V9 attenuated DSS-induced colitis against oxidative stress by up-regulating Trx-1 via activation of AMPK/FOXO3a pathway, suggesting that GL-V9 might be a potential effective drug for colitis.

Inhibition of Epithelial TNF-α Receptors by Purified Fruit Bromelain Ameliorates Intestinal Inflammation and Barrier Dysfunction in Colitis.

Science.gov (United States)

Zhou, Zijuan; Wang, Liang; Feng, Panpan; Yin, Lianhong; Wang, Chen; Zhi, Shengxu; Dong, Jianyi; Wang, Jingyu; Lin, Yuan; Chen, Dapeng; Xiong, Yongjian; Peng, Jinyong

2017-01-01

Activation of the TNF-α receptor (TNFR) leads to an inflammatory response, and anti-TNF therapy has been administered to reduce inflammation symptoms and heal mucosal ulcers in inflammatory bowel disease (IBD). Bromelain, a complex natural mixture of proteolytic enzymes, has been shown to exert anti-inflammatory effects. This study aimed to investigate the effect of purified fruit bromelain (PFB)-induced inhibition of epithelial TNFR in a rat colitis model. Colitis was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. Expression of TNFR1 and TNFR2 was measured by quantitative RT-PCR and western blotting. The effect of PFB on colitis was evaluated by examining the inflammatory response and intestinal epithelial barrier function. Our results showed that both TNFR1 and TNFR2 expression were significantly increased in a colitis model, and the increase was significantly reversed by PFB. Colitis symptoms, including infiltration of inflammatory cells, cytokine profiles, epithelial cell apoptosis, and epithelial tight junction barrier dysfunction were significantly ameliorated by PFB. Compared with fruit bromelain and stem bromelain complex, the inhibition of TNFR2 induced by PFB was stronger than that exhibited on TNFR1. These results indicate that PFB showed a stronger selective inhibitory effect on TNFR2 than TNFR1. In other words, purification of fruit bromelain increases its selectivity on TNFR2 inhibition. High expression of epithelial TNFRs in colitis was significantly counteracted by PFB, and PFB-induced TNFR inhibition ameliorated colitis symptoms. These results supply novel insights into potential IBD treatment by PFB.

Cathode spot movements along the carbon fibres in carbon/carbon composites

International Nuclear Information System (INIS)

Zhang Chengyu; Qiao Shengru; Yang Zhimao; Ding Bingjun

2007-01-01

The cathode spot movements on a polyacrilonitrile (PAN)-based carbon felt reinforced C/C composite and a three dimensional PAN-based carbon fibre reinforced C/C composite (3D-C/C) were investigated by a scanning electron microscope and a digital high-speed video camera. It was found that the carbon fibres have a higher ability to withstand the vacuum arc erosion than the carbon matrix. The cathode spot walks on the matrix, rather than on the carbon fibres. The cathode spot motion is controlled by the architecture of carbon fibres in C/C. The cathode spots move along the carbon fibres by a step-by-step manner rather than a random walk. The cathode spot tracks spread over a wide zone on the 3D-C/C surface parallel to the carbon fibre. The average arc spreading velocity is estimated to be about 0.9 m s -1 and the transient arc spreading velocity is in the range of 0.54-4.5 m s -1

Natural Composites: Cellulose Fibres and the related Performance of Composites

DEFF Research Database (Denmark)

Lilholt, Hans; Madsen, Bo

2014-01-01

Biobased materials are becoming of increasing interest as potential structural materials for the future. A useful concept in this context is the fibre reinforcement of materials by stiff and strong fibres. The biobased resources can contribute with cellulose fibres and biopolymers. This offers th...... in stiffness, on the packing ability of cellulose fibres and the related maximum fibre volume fraction in composites, on the moisture sorption of cellulose fibres and the related mass increase and (large) hygral strains induced, and on the mechanical performance of composites....

Changes in the composition of intestinal fungi and their role in mice with dextran sulfate sodium-induced colitis.

Science.gov (United States)

Qiu, Xinyun; Zhang, Feng; Yang, Xi; Wu, Na; Jiang, Weiwei; Li, Xia; Li, Xiaoxue; Liu, Yulan

2015-05-27

Intestinal fungi are increasingly believed to greatly influence gut health. However, the effects of fungi on intestinal inflammation and on gut bacterial constitution are not clear. Here, based on pyrosequencing method, we reveal that fungal compositions vary in different intestinal segments (ileum, cecum, and colon), prefer different colonization locations (mucosa and feces), and are remarkably changed during intestinal inflammation in dextran sulfate sodium (DSS)-colitis mouse models compare to normal controls: Penicillium, Wickerhamomyces, Alternaria, and Candida are increased while Cryptococcus, Phialemonium, Wallemia and an unidentified Saccharomycetales genus are decreased in the guts of DSS-colitis mice. Fungi-depleted mice exhibited aggravated acute DSS-colitis associated with gain of Hallella, Barnesiella, Bacteroides, Alistipes, and Lactobacillus and loss of butyrate-producing Clostridium XIVa, and Anaerostipes compare with normal control. In contrast, bacteria-depleted mice show attenuated acute DSS-colitis. Mice with severely chronic recurrent DSS-colitis show increased plasma (1,3)-β-D-glucan level and fungal translocation into the colonic mucosa, mesenteric lymph nodes and spleen. This work demonstrate the different roles of fungi in acute and chronic recurrent colitis: They are important counterbalance to bacteria in maintaining intestinal micro-ecological homeostasis and health in acutely inflamed intestines, but can harmfully translocate into abnormal sites and could aggravate disease severity in chronic recurrent colitis.

The probiotic mixture VSL#3 mediates both pro- and anti-inflammatory responses in bone marrow-derived dendritic cells from C57BL/6 and BALB/c mice

NARCIS (Netherlands)

Mariman, R.; Kremer, S.H.A.; Koning, F.; Nagelkerken, L.

2014-01-01

Probiotic bacteria express a wide range of molecular structures that bind to receptors on innate immune cells and mediate health-promoting effects in the host. We have recently demonstrated in a colitis model that favourable effects of the probiotic mixture VSL#3 may in part be due to the

How Common-and How Serious- Is Clostridium difficile Colitis After Geriatric Hip Fracture? Findings from the NSQIP Dataset.

Science.gov (United States)

Bovonratwet, Patawut; Bohl, Daniel D; Russo, Glenn S; Ondeck, Nathaniel T; Nam, Denis; Della Valle, Craig J; Grauer, Jonathan N

2018-03-01

Patients with geriatric hip fractures may be at increased risk for postoperative Clostridium difficile colitis, which can cause severe morbidity and can influence hospital quality metrics. However, to our knowledge, no large database study has calculated the incidence of, factors associated with, and effect of C. difficile colitis on geriatric patients undergoing hip fracture surgery. To use a large national database with in-hospital and postdischarge data (National Surgical Quality Improvement Program [NSQIP®]) to (1) determine the incidence and timing of C. difficile colitis in geriatric patients who underwent surgery for hip fracture, (2) identify preoperative and postoperative factors associated with the development of C. difficile colitis in these patients, and (3) test for an association between C. difficile colitis and postoperative length of stay, 30-day readmission, and 30-day mortality. This is a retrospective study. Patients who were 65 years or older who underwent hip fracture surgery were identified in the 2015 NSQIP database. The primary outcome was a diagnosis of C. difficile colitis during the 30-day postoperative period. Preoperative and procedural factors were tested for association with the development of C. difficile colitis through a backward stepwise multivariate model. Perioperative antibiotic type and duration were not included in the model, as this information was not recorded in the NSQIP. The association between C. difficile colitis and postoperative length of stay, 30-day readmission, and 30-day mortality were tested through multivariate regressions, which adjusted for preoperative and procedural characteristics such as age, comorbidities, and surgical procedure. A total of 6928 patients who were 65 years or older and underwent hip fracture surgery were identified. The incidence of postoperative C. difficile colitis was 1.05% (95% CI, 0.81%-1.29%; 73 of 6928 patients). Of patients who had C. difficile colitis develop, 64% (47 of 73

Positive correlation between disease activity index and matrix metalloproteinases activity in a rat model of colitis.

Science.gov (United States)

Oliveira, Luiz Gustavo de; Cunha, André Luiz da; Duarte, Amaury Caiafa; Castañon, Maria Christina Marques Nogueira; Chebli, Júlio Maria Fonseca; Aguiar, Jair Adriano Kopke de

2014-01-01

Inflammatory bowel disease, including ulcerative colitis and Crohn's disease, comprising a broad spectrum of diseases those have in common chronic inflammation of the gastrointestinal tract, histological alterations and an increased activity levels of certain enzymes, such as, metalloproteinases. Evaluate a possible correlation of disease activity index with the severity of colonic mucosal damage and increased activity of metalloproteinases in a model of ulcerative colitis induced by dextran sulfate sodium. Colitis was induced by oral administration of 5% dextran sulfate sodium for seven days in this group (n=10), whereas control group (n=16) received water. Effects were analyzed daily by disease activity index. In the seventh day, animals were euthanized and hematological measurements, histological changes (hematoxylin and eosin and Alcian Blue staining), myeloperoxidase and metalloproteinase activities (MMP-2 and MMP-9) were determined. Dextran sulfate sodium group showed elevated disease activity index and reduced hematological parameters. Induction of colitis caused tissue injury with loss of mucin and increased myeloperoxidase (Pcorrelation with the degree of histopathological changes after induction of colitis, and this result may be related mainly to the increased activity of MMP-9 and mieloperoxidase.

Sphingosine-1-phosphate mediates epidermal growth factor-induced muscle satellite cell activation

Energy Technology Data Exchange (ETDEWEB)

Nagata, Yosuke, E-mail: cynagata@mail.ecc.u-tokyo.ac.jp; Ohashi, Kazuya; Wada, Eiji; Yuasa, Yuki; Shiozuka, Masataka; Nonomura, Yoshiaki; Matsuda, Ryoichi

2014-08-01

Skeletal muscle can regenerate repeatedly due to the presence of resident stem cells, called satellite cells. Because satellite cells are usually quiescent, they must be activated before participating in muscle regeneration in response to stimuli such as injury, overloading, and stretch. Although satellite cell activation is a crucial step in muscle regeneration, little is known of the molecular mechanisms controlling this process. Recent work showed that the bioactive lipid sphingosine-1-phosphate (S1P) plays crucial roles in the activation, proliferation, and differentiation of muscle satellite cells. We investigated the role of growth factors in S1P-mediated satellite cell activation. We found that epidermal growth factor (EGF) in combination with insulin induced proliferation of quiescent undifferentiated mouse myoblast C2C12 cells, which are also known as reserve cells, in serum-free conditions. Sphingosine kinase activity increased when reserve cells were stimulated with EGF. Treatment of reserve cells with the D-erythro-N,N-dimethylsphingosine, Sphingosine Kinase Inhibitor, or siRNA duplexes specific for sphingosine kinase 1, suppressed EGF-induced C2C12 activation. We also present the evidence showing the S1P receptor S1P2 is involved in EGF-induced reserve cell activation. Moreover, we demonstrated a combination of insulin and EGF promoted activation of satellite cells on single myofibers in a manner dependent on SPHK and S1P2. Taken together, our observations show that EGF-induced satellite cell activation is mediated by S1P and its receptor. - Highlights: • EGF in combination with insulin induces proliferation of quiescent C2C12 cells. • Sphingosine kinase activity increases when reserve cells are stimulated with EGF. • EGF-induced activation of reserve cells is dependent on sphingosine kinase and ERK. • The S1P receptor S1P2 is involved in EGF-induced reserve cell activation. • EGF-induced reserve cell activation is mediated by S1P and its

Sphingosine-1-phosphate mediates epidermal growth factor-induced muscle satellite cell activation

International Nuclear Information System (INIS)

Nagata, Yosuke; Ohashi, Kazuya; Wada, Eiji; Yuasa, Yuki; Shiozuka, Masataka; Nonomura, Yoshiaki; Matsuda, Ryoichi

2014-01-01

Skeletal muscle can regenerate repeatedly due to the presence of resident stem cells, called satellite cells. Because satellite cells are usually quiescent, they must be activated before participating in muscle regeneration in response to stimuli such as injury, overloading, and stretch. Although satellite cell activation is a crucial step in muscle regeneration, little is known of the molecular mechanisms controlling this process. Recent work showed that the bioactive lipid sphingosine-1-phosphate (S1P) plays crucial roles in the activation, proliferation, and differentiation of muscle satellite cells. We investigated the role of growth factors in S1P-mediated satellite cell activation. We found that epidermal growth factor (EGF) in combination with insulin induced proliferation of quiescent undifferentiated mouse myoblast C2C12 cells, which are also known as reserve cells, in serum-free conditions. Sphingosine kinase activity increased when reserve cells were stimulated with EGF. Treatment of reserve cells with the D-erythro-N,N-dimethylsphingosine, Sphingosine Kinase Inhibitor, or siRNA duplexes specific for sphingosine kinase 1, suppressed EGF-induced C2C12 activation. We also present the evidence showing the S1P receptor S1P2 is involved in EGF-induced reserve cell activation. Moreover, we demonstrated a combination of insulin and EGF promoted activation of satellite cells on single myofibers in a manner dependent on SPHK and S1P2. Taken together, our observations show that EGF-induced satellite cell activation is mediated by S1P and its receptor. - Highlights: • EGF in combination with insulin induces proliferation of quiescent C2C12 cells. • Sphingosine kinase activity increases when reserve cells are stimulated with EGF. • EGF-induced activation of reserve cells is dependent on sphingosine kinase and ERK. • The S1P receptor S1P2 is involved in EGF-induced reserve cell activation. • EGF-induced reserve cell activation is mediated by S1P and its

Lupeol induces S-phase arrest and mitochondria-mediated ...

Indian Academy of Sciences (India)

48

Lupeol induces S-phase arrest and mitochondria-mediated apoptosis in cervical cancer cells. Nupoor Prasad1, Akash Sabarwal2, Umesh C. S. Yadav1, Rana P. Singh2,*. 1School of Life Sciences, Central University of Gujarat, Gandhinagar, Gujarat, India. 2Cancer Biology Laboratory, School of Life Sciences, Jawaharlal ...

Total glucosides of paeony ameliorates TNBS‑induced colitis by modulating differentiation of Th17/Treg cells and the secretion of cytokines.

Science.gov (United States)

Lin, Haihua; Zhang, Wenyou; Jiang, Xuepei; Chen, Renpin; Huang, Xielin; Huang, Zhiming

2017-12-01

The imbalance between effector CD4+ T helper 17 (Th17) and regulatory CD4+ T cells (Treg) cells and their associated cytokines, have been associated with the pathogenesis of inflammatory bowel disease (IBD). Total glycosides of paeony (TGP) is an alternative immunomodulatory agent that is widely used for the treatment of autoimmune diseases. The present study aimed to evaluate the modulatory effect of TGP in a rat model of colitis induced by 2,4,6‑trinitrobenzene sulfonic acid (TNBS). TGP was administered intragastrically 24 h after the TNBS intrarectal instillation for 7 days. TGP treatment ameliorated the clinical status and reversed the histopathologic severity of acute TNBS colitis. Furthermore, TGP inhibited the levels of Th17‑associated cytokines interleukin (IL)‑17, IL‑6, tumor necrosis factor‑α, whereas the expression levels of Treg‑associated cytokines IL‑10, transforming growth factor‑β in the plasma, colon, spleen and mesenteric lymph nodes (MLN). Additionally, TGP reduced the percentage of Th17 cells; however, the proportion of Treg cells in the spleen and MLN was increased. The present study also observed a suppression of Th17‑associated transcription factor, termed retinoid‑related orphan receptor‑γt (ROR‑γt). However, expression of the Treg‑associated transcription factor forkhead boxp3 was increased in the TGP treatment group. Therefore, the present findings suggest that TGP has a regulatory role in modulating the balance of Th17 and Treg cells to ameliorate the TNBS‑induced colitis and support the strategy of using TGP to treat IBD.

The magnetic properties of aligned M hexa-ferrite fibres

International Nuclear Information System (INIS)

Pullar, R.C.; Bhattacharya, A.K.

2006-01-01

Aligned and random fibres of strontium hexa ferrite (SrM, SrFe 12 O 19 ) and barium hexaferrite (BaM, BaFe 12 O 19 ) were manufactured by blow spinning from an aqueous inorganic sol-gel precursor, which was then fired to give the hexagonal ferrite fibre. Their magnetic properties were studied by VSM, investigating the evolution of these properties with firing and measurement temperature, and in particular the effects of fibre alignment. It has been predicted that aligned ferrite fibres will demonstrate an enhanced magnetisation along the axis of alignment with respect to perpendicular to the axis, and this has been demonstrated here for the first time. The optimum firing temperature was 1000 deg. C, at which point they still had submicron grains. In BaM random fibres M s =63.8 emu g -1 and H c =428.1 kA m -1 , and in SrM random fibres M s =63.3 emu g -1 and H c =452.8 kA m -1 , high values for polycrystalline materials. Fibres aligned parallel to the applied field had saturation magnetisation (M s ) values equal to those of the random fibres, whilst fibres aligned perpendicular to the field had M s values 62% and 75% lower, for BaM and SrM, respectively. There was no change in coercivity (H c ) between random or aligned fibres of any orientation, and fibres aligned 45 deg. and parallel to H appeared identical. Therefore, properties along the axis of alignment were superior when compared to measurements perpendicular to the axis of alignment, giving a directionality to the magnetisation in an otherwise randomly oriented ferrite material

Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer.

Directory of Open Access Journals (Sweden)

Emily L Lowe

2010-09-01

Full Text Available Inflammatory bowel disease (IBD is a disorder of chronic inflammation with increased susceptibility to colorectal cancer. The etiology of IBD is unclear but thought to result from a dysregulated adaptive and innate immune response to microbial products in a genetically susceptible host. Toll-like receptor (TLR signaling induced by intestinal commensal bacteria plays a crucial role in maintaining intestinal homeostasis, innate immunity and the enhancement of intestinal epithelial cell (IEC integrity. However, the role of TLR2 in the development of colorectal cancer has not been studied. We utilized the AOM-DSS model for colitis-associated colorectal cancer (CAC in wild type (WT and TLR2(-/- mice. Colons harvested from WT and TLR2(-/- mice were used for histopathology, immunohistochemistry, immunofluorescence and cytokine analysis. Mice deficient in TLR2 developed significantly more and larger colorectal tumors than their WT controls. We provide evidence that colonic epithelium of TLR2(-/- mice have altered immune responses and dysregulated proliferation under steady-state conditions and during colitis, which lead to inflammatory growth signals and predisposition to accelerated neoplastic growth. At the earliest time-points assessed, TLR2(-/- colons exhibited a significant increase in aberrant crypt foci (ACF, resulting in tumors that developed earlier and grew larger. In addition, the intestinal microenvironment revealed significantly higher levels of IL-6 and IL-17A concomitant with increased phospho-STAT3 within ACF. These observations indicate that in colitis, TLR2 plays a protective role against the development of CAC.

Temperature-dependent changes in the viscoelasticity of intact resting mammalian (rat) fast- and slow-twitch muscle fibres.

Science.gov (United States)

Mutungi, G; Ranatunga, K W

1998-04-01

1. The tension and sarcomere length responses induced by ramp stretches (at amplitudes of 1-3 % fibre length (Lo) and speeds of 0.01-12 Lo s-1) were examined at different temperatures (range, 10-35 degrees C) in resting intact muscle fibre bundles isolated from the soleus (a slow-twitch muscle) and extensor digitorum longus (a fast-twitch muscle) of the rat. Some observations are also presented on the effects of chemical skinning on passive viscoelasticity at 10 degrees C. 2. As previously reported, the tension response to a ramp stretch, in different preparations and under various conditions, could be resolved into a viscous (P1), a viscoelastic (P2) and an elastic (P3) component and showed characteristic differences between slow and fast muscle fibres. 3. Chemical skinning of the muscle fibres led to a decrease in the amplitude of all three tension components. However, the fast-slow fibre differences remained after skinning. For example, the viscosity coefficient derived from P1 tension data decreased from 0.84 +/- 0.06 before skinning to 0.44 +/- 0.06 kN s m-2 after skinning in fast fibres; the corresponding values in slow fibres were 2.1 +/- 0.08 and 0.87 +/- 0.09 kN s m-2, respectively. 4. Increasing the experimental temperature from 10 to 35 degrees C led to a decrease in all the tension components in both fast and slow muscle fibre bundles. The decrease of P1 (viscous) tension was such that the viscosity coefficient calculated using P1 data was reduced from 0.84 +/- 0.1 to 0.43 +/- 0.05 kN s m-2 in fast fibres and from 2.0 +/- 0.1 to 1.0 +/- 0.1 kN s m-2 in slow fibres (Q10 of approximately 1.3 in both). 5. In both fast and slow muscle fibre preparations, the plateau tension of the viscoelastic component (P2) decreased by 60-80 % as the temperature was increased from 10 to 35 degrees C giving P2 tension a Q10 of approximately 1.4 in slow fibres and approximately 1.7 in the fast fibres. Additionally, the relaxation time of the viscoelasticity decreased from

Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri.

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Gao, Chunxu; Major, Angela; Rendon, David; Lugo, Monica; Jackson, Vanessa; Shi, Zhongcheng; Mori-Akiyama, Yuko; Versalovic, James

2015-12-15

Probiotics and commensal intestinal microbes suppress mammalian cytokine production and intestinal inflammation in various experimental model systems. Limited information exists regarding potential mechanisms of probiotic-mediated immunomodulation in vivo. In this report, we demonstrate that specific probiotic strains of Lactobacillus reuteri suppress intestinal inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Only strains that possess the hdc gene cluster, including the histidine decarboxylase and histidine-histamine antiporter genes, can suppress colitis and mucosal cytokine (interleukin-6 [IL-6] and IL-1β in the colon) gene expression. Suppression of acute colitis in mice was documented by diminished weight loss, colonic injury, serum amyloid A (SAA) protein concentrations, and reduced uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG) in the colon by positron emission tomography (PET). The ability of probiotic L. reuteri to suppress colitis depends on the presence of a bacterial histidine decarboxylase gene(s) in the intestinal microbiome, consumption of a histidine-containing diet, and signaling via the histamine H2 receptor (H2R). Collectively, luminal conversion of l-histidine to histamine by hdc(+) L. reuteri activates H2R, and H2R signaling results in suppression of acute inflammation within the mouse colon. Probiotics are microorganisms that when administered in adequate amounts confer beneficial effects on the host. Supplementation with probiotic strains was shown to suppress intestinal inflammation in patients with inflammatory bowel disease and in rodent colitis models. However, the mechanisms of probiosis are not clear. Our current studies suggest that supplementation with hdc(+) L. reuteri, which can convert l-histidine to histamine in the gut, resulted in suppression of colonic inflammation. These findings link luminal conversion of dietary components (amino acid metabolism) by gut microbes and probiotic-mediated

Penta-acetyl geniposide-induced apoptosis involving transcription of NGF/p75 via MAPK-mediated AP-1 activation in C6 glioma cells

International Nuclear Information System (INIS)

Peng, C.-H.; Huang, C.-N.; Hsu, S.-P.; Wang, C.-J.

2007-01-01

We have demonstrated the herbal derivative penta-acetyl geniposide ((Ac) 5 GP) induces C6 glioma cell apoptosis through the critical sphingomyelinase (SMase)/nerve growth factor (NGF)/p75 and its downstream signals. It has been reported mitogen-activated protein kinase (MAPK) mediates NGF synthesis induced by SMase activation. In this study, ERK, p38 and JNK are shown to mediate (Ac) 5 GP-induced glioma cell apoptosis and elevation of NGF and p75. Treatment of PD98059 (ERK-specific inhibitor), SB203580 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor) decreases the elevation of NGF and p75 mRNA induced by (Ac) 5 GP, indicating possible transcription regulation via MAPKs. The results of nuclear extract blotting and EMSA further confirm (Ac) 5 GP maximally increases AP-1 and NF-κB DNA binding at 6 h. Inhibition of ERK, p38 and JNK block the activation of AP-1 and NF-κB, suggesting these MAPKs are involved in (Ac) 5 GP-induced transcription regulation. We thereby used RT-PCR to analyze cells treated with (Ac) 5 GP, with or without AP-1 or NF-κB inhibitors. AP-1 inhibitor NDGA decreases NGF/p75 and expression of FasL and caspase 3 induced by (Ac) 5 GP, suggesting the importance of AP-1 in mediating NGF/p75 and their downstream apoptotic signals. However, FasL and caspase 3 do not change with the NF-κB inhibitor PDTC; NF-κB might be linked to other cellular events. Overall, we demonstrate that MAPK mediates (Ac) 5 GP-induced activation of AP-1, promoting the transcription of NGF/p75 and downstream apoptotic signals. These results further highlight the potential therapeutic effects of (Ac) 5 GP in chemoprevention or as an anti-tumor agent

Radiation-resistance assessment of IR fibres for ITER thermography diagnostic system

International Nuclear Information System (INIS)

Brichard, B.; Ierschot, S. van; Ooms, H.; Berghmans, F.; Reichle, R.; Pocheau, C.; Decreton, M.

2006-01-01

The actively cooled target plates in the divertor of ITER will be subjected to high thermal fluxes (∼ 10 MW/m 2 ). These target plates are compound structures of an armour material at the surface - either carbon fibre reinforced carbon (CFC) or tungsten - and a water cooled CuCrZr structure inside or below. The thermal limit of the interface between the two materials must not exceed 550 o C. Therefore, the temperature must be carefully monitored to prevent structural damages of the divertor plates. Non contact measurements of the temperature offer the advantage to avoid weakening of the cooling plate structure which is already quite complex to manufacture. Infrared thermography of the target surface is therefore considered as a possible solution. Recently a diagnostic concept for spectrally resolved ITER divertor thermography using optical fibres has been proposed by CEA-Cadarache. However, the divertor region will have to face high-radiation flux and the radiation-resistance of InfraRed (IR)-fibres must be evaluated. In collaboration with CEA-Cadarache, an irradiation program has been started at SCK-CEN (Mol, Belgium) with the aim to measure the radiation-induced absorption of different IR fibre candidates operating in the 1-5 μm range. We selected various commercially available IR technologies: ZrF 4 , Hollow-Waveguide, Sapphire and Chalcogenide. For wavelengths below 2 μm we also tested low-OH silica fibres. We carried out a gamma irradiation at a maximum dose-rate of 0.42 Gy/s up to a total dose of about 5000 Gy. We showed that the optical transmission of ZrF 4 fibres strongly decreased under gamma radiation, primarily for wavelengths below 2 μm. In this type of fibre typical optical losses can reach 50 % at 5000 Gy around 3 μm. Nevertheless, the optical transmission can be significantly recovered by performing a thermal annealing treatment at a temperature of 100 o C. We also irradiated a Silver-coated hollow waveguide fibre at the same dose-rate but up

Soybean and fish oil mixture increases IL-10, protects against DNA damage and decreases colonic inflammation in rats with dextran sulfate sodium (DSS colitis

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Carvalho Patrícia O

2010-07-01

Full Text Available Abstract It was investigated whether dietary polyunsaturated fatty acids (PUFA could influence colonic injury, tissue DNA damage, cytokines and myeloperoxidase activity (MPO and plasma corticosterone in DSS-induced colitis rats. Male weaning Wistar rats were fed for 47 days with an AIN-93 diet with control (C, fish (F or a mixture of fish and soybean oil (SF. The colitis was induced from day 36 until day 42 by 3% DSS in drinking water. On day 48, blood samples were collected for corticosterone determination. The distal colon was excised for histological analysis and to quantify the cytokine (IL-4, IL-10 and INF-γ, MPO and DNA damage. The disease activity index (DAI was recorded daily during colitis induction. The DAI, MPO, histological analyses showed decreases only in the SF group compared with the C group. IL-10 was increased and DNA damage was reduced in the groups F and SF, and an inverse correlation between these variables was found. There were no differences in corticosterone, IFN-γ and IL-4 levels. Soybean and fish oil mixture may be effective in improving colonic injury and DNA damage, and it could be an important complementary therapy in UC to reduce the use of anti-inflammatory drugs and prevent colorectal cancer.

MTG16 contributes to colonic epithelial integrity in experimental colitis

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Williams, Christopher S; Bradley, Amber M; Chaturvedi, Rupesh; Singh, Kshipra; Piazuelo, Maria B; Chen, Xi; McDonough, Elizabeth M; Schwartz, David A; Brown, Caroline T; Allaman, Margaret M; Coburn, Lori A; Horst, Sara N; Beaulieu, Dawn B; Choksi, Yash A; Washington, Mary Kay; Williams, Amanda D; Fisher, Melissa A; Zinkel, Sandra S; Peek, Richard M; Wilson, Keith T; Hiebert, Scott W

2013-01-01

Objective The myeloid translocation genes (MTGs) are transcriptional corepressors with both Mtg8−/− and Mtgr1−/− mice showing developmental and/or differentiation defects in the intestine. We sought to determine the role of MTG16 in intestinal integrity. Methods Baseline and stress induced colonic phenotypes were examined in Mtg16−/− mice. To unmask phenotypes, we treated Mtg16−/− mice with dextran sodium sulphate (DSS) or infected them with Citrobacter rodentium and the colons were examined for ulceration and for changes in proliferation, apoptosis and inflammation. Results Mtg16−/− mice have altered immune subsets, suggesting priming towards Th1 responses. Mtg16−/− mice developed increased weight loss, diarrhoea, mortality and histological colitis and there were increased innate (Gr1+, F4/80+, CD11c+ and MHCII+; CD11c+) and Th1 adaptive (CD4) immune cells in Mtg16−/− colons after DSS treatment. Additionally, there was increased apoptosis and a compensatory increased proliferation in Mtg16−/− colons. Compared with wild-type mice, Mtg16−/− mice exhibited increased colonic CD4;IFN-γ cells in vehicle-treated and DSS-treated mice. Adoptive transfer of wildtype marrow into Mtg16−/− recipients did not rescue the Mtg16−/− injury phenotype. Isolated colonic epithelial cells from DSS-treated Mtg16−/− mice exhibited increased KC (Cxcl1) mRNA expression when compared with wild-type mice. Mtg16−/− mice infected with C rodentium had more severe colitis and greater bacterial colonisation. Last, MTG16 mRNA levels were reduced in human ulcerative colitis versus normal colon tissues. Conclusions These observations indicate that MTG16 is critical for colonocyte survival and regeneration in response to intestinal injury and provide evidence that this transcriptional corepressor regulates inflammatory recruitment in response to injury. PMID:22833394

miR-19a promotes colitis-associated colorectal cancer by regulating tumor necrosis factor alpha-induced protein 3-NF-κB feedback loops.

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Wang, T; Xu, X; Xu, Q; Ren, J; Shen, S; Fan, C; Hou, Y

2017-06-08

Chronic inflammation is believed to have a crucial role in colon cancer development. MicroRNA (miRNA) deregulation is common in human colorectal cancers, but little is known regarding whether miRNA drives tumor progression by regulating inflammation. Here, we showed that miR-19a can promote colitis and colitis-associated colon cancer (CAC) development using a CAC mouse model and an acute colitis mouse model. Tumor necrosis factor-α (TNF-α) stimulation can increase miR-19a expression, and upregulated miR-19a can in turn activate nuclear factor (NF)-κB signaling and TNF-α production by targeting TNF alpha-induced protein 3 (TNFAIP3). miR-19a inhibition can also alleviate CAC in vivo. Moreover, the regulatory effects of miR-19a on TNFAIP3 and NF-κB signaling were confirmed using tumor samples from patients with colon cancer. These new findings demonstrate that miR-19a has a direct role in upregulating NF-κB signaling and that miR-19a has roles in inflammation and CAC.

Cutaneous nociceptors lack sensitisation, but reveal μ-opioid receptor-mediated reduction in excitability to mechanical stimulation in neuropathy

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Schmidt Yvonne

2012-11-01

Full Text Available Abstract Background Peripheral nerve injuries often trigger a hypersensitivity to tactile stimulation. Behavioural studies demonstrated efficient and side effect-free analgesia mediated by opioid receptors on peripheral sensory neurons. However, mechanistic approaches addressing such opioid properties in painful neuropathies are lacking. Here we investigated whether opioids can directly inhibit primary afferent neuron transmission of mechanical stimuli in neuropathy. We analysed the mechanical thresholds, the firing rates and response latencies of sensory fibres to mechanical stimulation of their cutaneous receptive fields. Results Two weeks following a chronic constriction injury of the saphenous nerve, mice developed a profound mechanical hypersensitivity in the paw innervated by the damaged nerve. Using an in vitro skin-nerve preparation we found no changes in the mechanical thresholds and latencies of sensory fibres from injured nerves. The firing rates to mechanical stimulation were unchanged or reduced following injury. Importantly, μ-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly5]-ol-enkephalin (DAMGO significantly elevated the mechanical thresholds of nociceptive Aδ and C fibres. Furthermore, DAMGO substantially diminished the mechanically evoked discharges of C nociceptors in injured nerves. These effects were blocked by DAMGO washout and pre-treatment with the selective μ-opioid receptor antagonist Cys2-Tyr3-Orn5-Pen7-amide. DAMGO did not alter the responses of sensory fibres in uninjured nerves. Conclusions Our findings suggest that behaviourally manifested neuropathy-induced mechanosensitivity does not require a sensitised state of cutaneous nociceptors in damaged nerves. Yet, nerve injury renders nociceptors sensitive to opioids. Prevention of action potential generation or propagation in nociceptors might represent a cellular mechanism underlying peripheral opioid-mediated alleviation of mechanical hypersensitivity in neuropathy.

Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression

DEFF Research Database (Denmark)

Wang, Zhipeng; Jin, Haifeng; Xu, Ruodan

2009-01-01

ability to block progress of colitis to colon cancer, and its molecular mechanism of action are investigated. A mouse model for colitis-induced colorectal cancer was used to test the effect of triptolide on cancer progression. Treatment of mice with triptolide decreased the incidence of colon cancer...... formation, and increased survival rate. Moreover, triptolide decreased the incidence of tumors in nude mice inoculated with cultured colon cancer cells dose-dependently. In vitro, triptolide inhibited the proliferation, migration and colony formation of colon cancer cells. Secretion of IL6 and levels of JAK....... This suggests that triptolide might be a candidate for prevention of colitis induced colon cancer because it reduces inflammation and prevents tumor formation and development....

The Healing Effect of Hydroalcoholic Extract of Hypericum Perforatum on Acetic Acid-Induced Ulcerative Colitis in Male Rats

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Nader Tanideh

2017-02-01

Full Text Available Background & Objective: Anti-inflammatory effect of Hypericum have long been considered. Ulcerative Colitis (UC is a form of Inflammatory Bowel Disease (IBD. In this study, the effects of Hypericum perforatum on histopathological changes and tissue malondialdehyde (MDA level of colonic tissue in rats with induced UC were evaluated. Materials & Methods: 70 rats were divided into seven equal groups. Colitis was induced by acetic acid.. Groups I and II received 1 mL of 600 and 300 mg/kg H. perforatum extract orally per day respectively; groups III and IV received 1 mL of 20% and 10% intra-colonic gel form of H. perforatum extract daily respectively; group V, as positive control, received 1 mL of intra-colonic Asacol; group VI received 1 mL of normal saline as negative control; group VII received just intra-colonic gel base. All the animals were evaluated for histological changes and tissue MDA level of colon seven days after the treatment. Results: H. perforatum extract in the two forms of trans-rectal and oral administration could result in a more healing effect on acetic acid-induced damaged colonic tissue with a reduction in the MDA activity. In trans-rectal administration, the 20% gel had a better healing response than the 10% gel. In oral administration, the 600 mg/kg dosage had a better healing response than the 300 mg/kg. Conclusions: Therefor, H. perforatum can be considered as a treatment of choice for UC especially in trans-rectal gel form.

Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer.

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Eva Pastille

2017-09-01

Full Text Available Inflammatory bowel diseases (IBD are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host's immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs. This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation. On the contrary, specific parasite infections are well known to be directly linked to carcinogenesis. Whether a helminth infection interferes with the development of colitis-associated colon cancer (CAC is not yet known. In the present study, we demonstrate that the treatment of mice with the intestinal helminth Heligmosomoides polygyrus at the onset of tumor progression in a mouse model of CAC does not alter tumor growth and distribution. In contrast, H. polygyrus infection in the early inflammatory phase of CAC strengthens the inflammatory response and significantly boosts tumor development. Here, H. polygyrus infection was accompanied by long-lasting alterations in the colonic immune cell compartment, with reduced frequencies of colonic CD8+ effector T cells. Moreover, H. polygyrus infection in the course of dextran sulfate sodium (DSS mediated colitis significantly exacerbates intestinal inflammation by amplifying the release of colonic IL-6 and CXCL1. Thus, our findings indicate that the therapeutic application of helminths during CAC might have tumor-promoting effects and therefore should be well-considered.

Protective effects of polyphenol-rich infusions from carob (Ceratonia siliqua) leaves and cladodes of Opuntia ficus-indica against inflammation associated with diet-induced obesity and DSS-induced colitis in Swiss mice.

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Aboura, Ikram; Nani, Abdelhafid; Belarbi, Meriem; Murtaza, Babar; Fluckiger, Aurélie; Dumont, Adélie; Benammar, Chahid; Tounsi, Moufida Saidani; Ghiringhelli, François; Rialland, Mickaël; Khan, Naim Akhtar; Hichami, Aziz

2017-12-01

In the present study, we have investigated the effects of polyphenol-rich infusions from carob leaves and OFI-cladodes on inflammation associated with obesity and dextran sulfate sodium (DSS)-induced ulcerative colitis in Swiss mice. In vitro studies revealed that aqueous extracts of carob leaves and OFI-cladodes exhibited anti-inflammatory properties marked by the inhibition of IL-6, TNF-α and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells concomitant with NF-κβ nucleus translocation inhibition. For in vivo investigations, Swiss male mice were subjected to control or high fat diet (HFD). At the 8th week after the start of study, animals received or not 1% infusion of either carob leaves or OFI-cladode for 4 weeks and were subjected to 2% DSS administration in drinking water over last 7 days. After sacrifice, pro-inflammatory cytokines levels in plasma and their mRNA expression in different organs were determined. Results showed that carob leaf and OFI-cladode infusions reduced inflammation severity associated with HFD-induced obesity and DSS-induced acute colitis indicated by decrease in pro-inflammatory cytokines expression (as such TNF-α, IL1b and IL-6) in colon, adipose tissue and spleen. In addition, plasma levels of IL-6 and TNF-α were also curtailed in response to infusions treatment. Thus, carob leaf and OFI-cladode infusions prevented intestinal permeability through the restoration of tight junction proteins (Zo1, occludins) and immune homeostasis. Hence, the anti-inflammatory effect of carob leaves and OFI-cladodes could be attributed to their polyphenols which might alleviate inflammation severity associated with obesity and colitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cooked navy and black bean diets improve biomarkers of colon health and reduce inflammation during colitis.

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

2014-05-01

Common beans contain non-digestible fermentable components (SCFA precursors) and phenolic compounds (phenolic acids, flavonoids and anthocyanins) with demonstrated antioxidant and anti-inflammatory potential. The objective of the present study was to assess the in vivo effect of cooked whole-bean flours, with differing phenolic compound levels and profiles, in a mouse model of acute colitis. C57BL/6 mice were fed a 20 % navy bean or black bean flour-containing diet or an isoenergetic basal diet (BD) for 2 weeks before the induction of experimental colitis via 7 d dextran sodium sulphate (DSS, 2 % (w/v) in the drinking-water) exposure. Compared with the BD, both bean diets increased caecal SCFA and faecal phenolic compound concentrations (Pdiets reduced mRNA expression of colonic inflammatory cytokines (IL-6, IL-9, IFN-γ and IL-17A) and increased anti-inflammatory IL-10 (Pdiets enhanced DSS-induced colonic damage as indicated by an increased histological injury score and apoptosis (cleaved caspase-3 and FasL mRNA expression) (Pdiets exerted both beneficial and adverse effects during experimental colitis by reducing inflammatory biomarkers both locally and systemically while aggravating colonic mucosal damage. Further research is required to understand the mechanisms through which beans exert their effects on colonic inflammation and the impact on colitis severity in human subjects.

cAMP-induced activation of protein kinase A and p190B RhoGAP mediates down-regulation of TC10 activity at the plasma membrane and neurite outgrowth.

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Koinuma, Shingo; Takeuchi, Kohei; Wada, Naoyuki; Nakamura, Takeshi

2017-11-01

Cyclic AMP plays a pivotal role in neurite growth. During outgrowth, a trafficking system supplies membrane at growth cones. However, the cAMP-induced signaling leading to the regulation of membrane trafficking remains unknown. TC10 is a Rho family GTPase that is essential for specific types of vesicular trafficking. Recent studies have shown a role of TC10 in neurite growth in NGF-treated PC12 cells. Here, we investigated a mechanical linkage between cAMP and TC10 in neuritogenesis. Plasmalemmal TC10 activity decreased abruptly after cAMP addition in neuronal cells. TC10 was locally inactivated at extending neurite tips in cAMP-treated PC12 cells. TC10 depletion led to a decrease in cAMP-induced neurite outgrowth. Constitutively active TC10 could not rescue this growth reduction, supporting our model for a role of GTP hydrolysis of TC10 in neuritogenesis by accelerating vesicle fusion. The cAMP-induced TC10 inactivation was mediated by PKA. Considering cAMP-induced RhoA inactivation, we found that p190B, but not p190A, mediated inactivation of TC10 and RhoA. Upon cAMP treatment, p190B was recruited to the plasma membrane. STEF depletion and Rac1-N17 expression reduced cAMP-induced TC10 inactivation. Together, the PKA-STEF-Rac1-p190B pathway leading to inactivation of TC10 and RhoA at the plasma membrane plays an important role in cAMP-induced neurite outgrowth. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Oral administration of Lentinus edodes β-glucans ameliorates DSS-induced ulcerative colitis in mice via MAPK-Elk-1 and MAPK-PPARγ pathways.

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Shi, Limin; Lin, Qinlu; Yang, Tao; Nie, Ying; Li, Xinhua; Liu, Bo; Shen, Junjun; Liang, Ying; Tang, Yiping; Luo, Feijun

2016-11-09

To evaluate the anti-inflammatory effect of β-glucans from Lentinus edodes, and its molecular mechanism, the dextran sulfate sodium salt (DSS) induced colitis model of mice and the LPS-stimulated RAW264.7 cell inflammation model were used in this study. 40 ICR male mice were randomly divided into 4 groups: Control, DSS (DSS treated only), DSS + low-βGs (500 mg kg -1 d -1 ) and DSS + high-βGs (1000 mg kg -1 d -1 ). The body weight of the mice with Lentinus edodes β-glucan supplementation increased significantly compared to the DSS group and the disease activity index (DAI) was improved in both βG-treated groups. Compared with the DSS group, histopathological analysis showed that the infiltration of inflammatory cells of both βG-treated groups decreased significantly in colonic tissues. Furthermore, oral administration of β-glucans decreases the concentration of malondialdehyde (MDA) and myeloperoxidase (MPO) and inhibits the expression of iNOS and several inflammatory factors: TNF-α, IL-1β and IL-6 as well as nitric oxide (NO) of the colonic tissues. The mitogen-activated protein kinase (MAPK) pathway is closely related to the expression of pro-inflammatory factors. In the DSS-induced colitis model and the LPS-stimulated RAW264.7 cell model, βGs inhibited the expression of pro-inflammatory factors and blocked the phosphorylation of JNK/ERK1/2 and p38; βGs also suppress the phosphorylation of Elk-1 at Ser84 and the phosphorylation of PPARγ at Ser112. Altogether, these results suggest that Lentinus edodes βGs could inhibit the DSS-induced ulcerative colitis and decrease inflammatory factor expressions. The molecular mechanism may be involved in suppressing MAPK signaling and inactivation of Elk-1 and activation of PPARγ.

TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA sensing.

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Seo, Gil Ju; Kim, Charlotte; Shin, Woo-Jin; Sklan, Ella H; Eoh, Hyungjin; Jung, Jae U

2018-02-09

Intracellular nucleic acid sensors often undergo sophisticated modifications that are critical for the regulation of antimicrobial responses. Upon recognition of DNA, the cytosolic sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the second messenger cGAMP, which subsequently initiates downstream signaling to induce interferon-αβ (IFNαβ) production. Here we report that TRIM56 E3 ligase-induced monoubiquitination of cGAS is important for cytosolic DNA sensing and IFNαβ production to induce anti-DNA viral immunity. TRIM56 induces the Lys335 monoubiquitination of cGAS, resulting in a marked increase of its dimerization, DNA-binding activity, and cGAMP production. Consequently, TRIM56-deficient cells are defective in cGAS-mediated IFNαβ production upon herpes simplex virus-1 (HSV-1) infection. Furthermore, TRIM56-deficient mice show impaired IFNαβ production and high susceptibility to lethal HSV-1 infection but not to influenza A virus infection. This adds TRIM56 as a crucial component of the cytosolic DNA sensing pathway that induces anti-DNA viral innate immunity.

Usefulness of colonoscopy in ischemic colitis Utilidad de la colonoscopia en la colitis isquémica

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M. Lozano Maya

2010-08-01

colonoscopia y biopsia, en un periodo de tiempo de cinco años. Se analizaron: edad, sexo, motivo de exploración, factores de riesgo cardiovascular, grado endoscópico de isquemia, cambio en la actitud terapéutica, tratamiento y evolución. Resultados: la edad media de nuestros pacientes fue de 73,6 ± 12,1 años con una incidencia similar en ambos sexos (50,9% mujeres y 49,1% hombres. Los factores de riesgo asociados fueron la hipertensión arterial (61,1%, el tabaco (37,2% y antecedente de accidente cardiovascular previo (52,2%. El motivo más frecuente de realización de colonoscopia fue rectorragia (53,6% seguido de dolor abdominal (30,4%, realizándose de forma urgente en el 65,3% de los casos. La colonoscopia permitió un cambio en la actitud terapéutica en el 50% de los casos, aumentando en la urgente al 65,75%. La mortalidad global fue del 27,67%. La colitis isquémica grave (25% fue más frecuente en varones (64,3%, y cuando la indicación de colonoscopia fue urgente (85,71% y cursó con mortalidad alta (53,57%. En estos se realizó tratamiento quirúrgico en el 57,14% de los casos con una evolución favorable en el 50%, mientras que los pacientes con colitis isquémica leve o moderada tuvieron un pronóstico mejor, con evolución favorable en el 80,95% de los casos y con menor requerimiento de tratamiento quirúrgico (4,76%, p < 0,05. Conclusión: la colitis isquémica es más frecuente en la edad avanzada. La sintomatología más común es la rectorragia y el dolor abdominal. La colonoscopia permite evaluar la gravedad e induce un cambio de actitud según el resultado de la misma. La evidencia de una colitis grave supuso un aumento de la necesidad de cirugía y peor pronóstico.

Therapeutic effect of hydroxychloroquine on colorectal carcinogenesis in experimental murine colitis.

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Yao, Junlin; Xie, Jiansheng; Xie, Binbin; Li, Yiran; Jiang, Liming; Sui, Xinbing; Zhou, Xiaoyun; Pan, Hongming; Han, Weidong

2016-09-01

Chronic inflammation in the intestine is a strong risk factor for colitis-associated colorectal cancer (CAC). Hydroxychloroquine (HCQ) is widely used as an anti-inflammatory drug in the treatment of immune-mediated inflammatory disorders and various tumors. However, little is known regarding the effects of HCQ on colitis-associated tumorigenesis. In this study, mice treated with HCQ showed a significant reduction in early-stage colitis following azoxymethane (AOM)/dextran sodium sulfate (DSS) administration, as well as a remarkable inhibition of colonic tumorigenesis and tumor growth at late stages of CAC. Mechanistically, the therapeutic effects of HCQ were attributed to inhibition of inflammatory responses and production of mutagenic reactive oxygen species (ROS) in immune cells and subsequent promotion of apoptosis and cell cycle arrest in tumor cells. Furthermore, we found that HCQ inhibited the production of inflammatory cytokines and ROS in response to toll-like receptor 4 (TLR4) activation in macrophages. Our data presented herein may help guide the clinical use of HCQ as a prevention and treatment strategy for CAC. Copyright © 2016 Elsevier Inc. All rights reserved.

Anti-Inflammatory Effects of Ethanol Extract of Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), in Mice with Ulcerative Colitis.

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Qin, Mingming; Geng, Yan; Lu, Zhenming; Xu, Hongyu; Shi, Jin-Song; Xu, Xin; Xu, Zheng-Hong

2016-01-01

This study investigated the anti-inflammatory activity of ethanol extracts of Hericium erinaceus in the inflammatory bowel disease (IBD) model. Twenty C57BL/6 mice were exposed to 2% (w/v) dextran sulfate sodium (DSS) in their drinking water for 7 d to induce acute intestinal inflammation. Orally administrated ethanol extract of H. erinaceus (HEEE) (250 mg/kg/d and 500 mg/kg/d body weight) could significantly (P < 0.05) improve body weight and colon length and decreased the intestinal bleeding of DSS-treated mice compared with DSS-treated mice not given HEEE. HEEE markedly reduced DSS-induced myeloperoxidase accumulation in colon tissues, attenuated histological change in the neutrophils and lymphocyte infiltration, and protected the mucosal epithelium. Mechanistically, HEEE ameliorated colitis not only by suppressing the production of inflammatory mediators including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in colon tissues but also by adjusting the production of nitric oxide, malondialdehyde, and superoxide dismutase in serum to suppress the oxidative stress. These results suggest that HEEE can be applied as a protective agent in the treatment of IBDs.