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Sample records for rat colitis model

  1. Sensory and inflammatory colonic changes induced by vincristine in distinct rat models of colitis.

    PubMed

    Viana-Cardoso, K V; Silva, M T B; Peixoto-Junior, A A; Marinho, L S; Matias, N S; Soares, P M G; Santos, A A; Brito, G A C; Rola, F H; Gondim, F de A A

    2015-04-01

    Preclinical and clinical studies show that gastrointestinal (GI) inflammation can evoke sensory changes occasionally far from the original inflammatory site. Animal models of colitis with either trinitrobenzenesulphonic acid (TNBS) or mustard oil (MO) produce distinct patterns of somatic and visceral sensory changes. We evaluated the effects of four doses of i.v. vincristine 150 μg kg(-1) (total of 600 μg kg(-1) ) treatment on the somatic (thermal nociceptive threshold) and colonic (morphological) changes induced by TNBS or MO in rats. TNBS and MO groups were further submitted to vincristine or saline pretreatments. TNBS induced somatic hypersensitivity, while MO induced somatic hyposensitivity (P < 0.05) when compared to the saline and ethanol control groups. Vincristine per se induced somatic hypersensitivity (P < 0.05). This effect was enhanced by TNBS and reversed by MO treatments. Although vincristine increased the colitis area (colonic weight length(-1) ratio) and the Morris' score in TNBS-treated rats, it did not alter the colitis area and even lowered the Morris' score in MO-treated rats. Compared to the saline (control) group, vincristine did not alter the colonic microscopic pattern. However, such lesions scores are higher (P < 0.05) in colitis groups induced by TNBS and MO, pretreated or not with vincristine. In conclusion, the somatic changes induced by different models of experimental colitis are diverse and modulated differently by vincristine.

  2. Hepatocyte growth factor, hepatocyte growth factor activator and arginine in a rat fulminant colitis model

    PubMed Central

    Zwintscher, Nathan P.; Shah, Puja M.; Salgar, Shashikumar K.; Newton, Christopher R.; Maykel, Justin A.; Samy, Ahmed; Jabir, Murad; Steele, Scott R.

    2016-01-01

    Introduction Dextran sodium sulfate (DSS) is commonly used to induce a murine fulminant colitis model. Hepatocyte growth factor (HGF) has been shown to decrease the symptoms of inflammatory bowel disease (IBD) but the effect of its activator, HGFA, is not well characterized. Arginine reduces effects of oxidative stress but its effect on IBD is not well known. The primary aim is to determine whether HGF and HGFA, or arginine will decrease IBD symptoms such as pain and diarrhea in a DSS-induced fulminant colitis murine model. Methods A severe colitis was induced in young, male Fischer 344 rats with 4% (w/v) DSS oral solution for seven days; rats were sacrificed on day 10. Rats were divided into five groups of 8 animals: control, HGF (700 mcg/kg/dose), HGF and HGFA (10 mcg/dose), HGF and arginine, and high dose HGF (2800 mcg/kg/dose). Main clinical outcomes were pain, diarrhea and weight loss. Blinded pathologists scored the terminal ileum and distal colon. Results DSS reliably induced severe active colitis in 90% of animals (n = 36/40). There were no differences in injury scores between control and treatment animals. HGF led to 1.38 fewer days in pain (p = 0.036), while arginine led to 1.88 fewer days of diarrhea (P = 0.017) compared to controls. 88% of HGFA-treated rats started regaining weight (P < 0.001). Discussion/Conclusion Although treatment was unable to reverse fulminant disease, HGF and arginine were associated with decreased days of pain and diarrhea. These clinical interventions may reduce associated symptoms for severe IBD patients, even when urgent surgical intervention remains the only viable option. PMID:27144006

  3. Salvianolic Acid B Restored Impaired Barrier Function via Downregulation of MLCK by microRNA-1 in Rat Colitis Model

    PubMed Central

    Xiong, Yongjian; Wang, Jingyu; Chu, Hongwei; Chen, Dapeng; Guo, Huishu

    2016-01-01

    Salvianolic acid B (Sal B) is isolated from the traditional Chinese medical herb Salvia miltiorrhiza and is reported to have a wide range of therapeutic benefits. The aim of this study was to investigate the effects of Sal B on epithelial barrier dysfunction in rat colitis and to uncover related mechanisms. Rat colitis model was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The intestinal barrier function was evaluated by measuring the serum recovery of fluorescein isothiocyanate-4 kD dextran in vivo and transepithelial electrical resistance in vitro respectively. The protein expression related to intestinal barrier function was studied using western blotting. The effects of Sal B on inflammatory responses, oxidative damage and colitis recurrence were also studied in this study. The intestinal barrier dysfunction in colitis was reversed by Sal B, accompanied with the decrease of tight junction proteins, and the effect could be blocked by microRNA-1(miR-1) inhibition. The inflammatory responses, oxidative damage and colitis recurrence were also decreased by Sal B. The colitis symptoms and recurrences were ameliorated by Sal B, and restoration of impaired barrier function via downregulation of MLCK by miR-1 maybe involved in this effect. This study provides some novel insights into both of the pathological mechanisms and treatment alternatives of inflammatory bowel disease. PMID:27303297

  4. Salvianolic Acid B Restored Impaired Barrier Function via Downregulation of MLCK by microRNA-1 in Rat Colitis Model.

    PubMed

    Xiong, Yongjian; Wang, Jingyu; Chu, Hongwei; Chen, Dapeng; Guo, Huishu

    2016-01-01

    Salvianolic acid B (Sal B) is isolated from the traditional Chinese medical herb Salvia miltiorrhiza and is reported to have a wide range of therapeutic benefits. The aim of this study was to investigate the effects of Sal B on epithelial barrier dysfunction in rat colitis and to uncover related mechanisms. Rat colitis model was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The intestinal barrier function was evaluated by measuring the serum recovery of fluorescein isothiocyanate-4 kD dextran in vivo and transepithelial electrical resistance in vitro respectively. The protein expression related to intestinal barrier function was studied using western blotting. The effects of Sal B on inflammatory responses, oxidative damage and colitis recurrence were also studied in this study. The intestinal barrier dysfunction in colitis was reversed by Sal B, accompanied with the decrease of tight junction proteins, and the effect could be blocked by microRNA-1(miR-1) inhibition. The inflammatory responses, oxidative damage and colitis recurrence were also decreased by Sal B. The colitis symptoms and recurrences were ameliorated by Sal B, and restoration of impaired barrier function via downregulation of MLCK by miR-1 maybe involved in this effect. This study provides some novel insights into both of the pathological mechanisms and treatment alternatives of inflammatory bowel disease. PMID:27303297

  5. Trefoil peptide TFF2 (spasmolytic polypeptide) potently accelerates healing and reduces inflammation in a rat model of colitis

    PubMed Central

    Tran, C; Cook, G; Yeomans, N; Thim, L; Giraud, A

    1999-01-01

    BACKGROUND—The trefoil peptides are major secretory products of mucus cells of the gastrointestinal tract and show increased expression after inflammatory or ulcerative damage. Recombinant human TFF2 (spasmolytic polypeptide) has been shown to be cytoprotective, and enhances repair in models of gastric injury. 
AIMS—To test the healing effects of recombinant human (h)TFF2 in a rat model of chronic colitis. 
METHODS—Colitis was induced by intracolonic administration of dinitrobenzene sulphonic acid in ethanol. Mucosal repair was quantified macroscopically, microscopically by image analysis of tissue histology, and by measuring myeloperoxidase activity. 
RESULTS—Initial validation studies showed that maximal injury and inflammation occurred at the end of the first week after colitis induction (active phase), and that spontaneous healing was complete by eight weeks. Once daily intrarectal application of hTFF2 (2.5 mg/kg; approximately 0.5 mg/rat) for five days after maximal damage had been sustained, reduced both microscopic and macroscopic injury by 80% and inflammatory index by 50% compared with vehicle controls. In addition, endogenous concentrations of rat TFF2 and TFF3 (intestinal trefoil factor) were increased in the active phase of colitis and were reduced to basal levels by hTFF2 treatment. 
CONCLUSIONS—This study has shown that hTFF2 enhances the rate of colonic epithelial repair, and reduces local inflammation in a rat model of colitis, and suggests that luminal application of trefoil peptides may have therapeutic potential in the treatment of inflammatory bowel disease. 

 Keywords: trefoil peptide; TFF2; spasmolytic polypeptide; colitis; repair PMID:10205199

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

    PubMed

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

    2016-06-01

    This study evaluated the effects of Pistacia atlantica (P. atlantica), butyrate, Lactobacillus casei (L. casei) and especially their combination therapy on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced rat colitis model. Rats were divided into seven groups. Four groups received oral P. atlantica, butyrate, L. casei and the combination of three agents for 10 consecutive days. The remaining groups were negative and positive controls and a sham group. Macroscopic and histopathological examinations were carried out along with determination of the specific biomarker of colonic oxidative stress, the myeloperoxidase (MPO). Compared with controls, the combination therapy exhibited a significant alleviation of colitis in terms of pathological scores and reduction of MPO activity (55%, p=0.0009). Meanwhile, the macroscopic appearance such as stool consistency, tissue and histopathological scores (edema, necrosis and neutrophil infiltration) were improved. Although single therapy by each P. atlantica, butyrate, and L. casei was partially beneficial in reduction of colon oxidative stress markers, the combination therapy was much more effective. In conclusion, the combination therapy was able to reduce the severity of colitis that is clear from biochemical markers. Future studies have to focus on clinical effects of this combination in management of human ulcerative colitis. Further molecular and signaling pathway studies will help to understand the mechanisms involved in the treatment of colitis and inflammatory diseases. PMID:26972417

  7. Effect of aqueous and particulate silk fibroin in a rat model of experimental colitis.

    PubMed

    Rodriguez-Nogales, A; Lozano-Pérez, A A; Aznar-Cervantes, S D; Algieri, F; Garrido-Mesa, J; Garrido-Mesa, N; Vezza, T; Utrilla, M P; Cenis, J L; Rodríguez-Cabezas, M E; Gálvez, J

    2016-09-10

    Silk fibroin (SF) has anti-inflammatory properties and promotes wound healing. Moreover, SF particles act as carriers of active drugs against intestinal inflammation due to their capacity to deliver the compound to the damaged colonic tissue. The present work assesses the effect of SF in the trinitrobenzenesulfonic acid model of rat colitis that resembles human intestinal inflammation. SF (8mg/kg) was administered in aqueous solution orally and in two particulate formats by intrarectal route, following two technologies: spray drying to make microparticles and desolvation in organic solvent to produce nanoparticles. SF treatments ameliorated the colonic damage, reduced neutrophil infiltration and improved the compromised oxidative status of the colon. They also reduced the gene expression of pro-inflammatory cytokines like IL-1β and the anti-inflammatory cytokine IL-10. Moreover, they improved the intestinal wall integrity by increasing the gene expression of some of its markers (villin, trefoil factor-3 and mucins), thus accelerating the healing. The immunomodulatory properties of SF particles were also tested in vitro in macrophages: they activated the immune response in basal conditions without increasing it after a pro-inflammatory insult. In conclusion, SF particles could be useful as carriers to deliver active drugs to the damaged intestinal colon with additional anti-inflammatory and healing properties. PMID:27363935

  8. Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats

    PubMed Central

    Senol, Altug; Isler, Mehmet; Sutcu, Recep; Akin, Mete; Cakir, Ebru; Ceyhan, Betul M; Kockar, M Cem

    2015-01-01

    AIM: To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. METHODS: Twenty-four male Wistar-albino rats were randomized into four groups: normal control, kefir-control, colitis, and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 mL kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo (skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index (DAI), based on daily weight loss, stool consistency, and presence of bleeding in feces. Rats were sacrificed on the 15th day, blood specimens were collected, and colon tissues were rapidly removed. Levels of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-10, malondialdehyde, and inducible nitric oxide synthase (iNOS) were measured in colon tissue. RESULTS: The DAI was lower in the kefir-colitis group than in the colitis group (on the 3rd and 5th days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6th day in the kefir-colitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores (P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group (P < 0

  9. In Vivo Evaluation of 5-ASA Colon-Specific Tablets Using Experimental-Induced Colitis Rat Animal Model.

    PubMed

    Sawarkar, Sujata P; Deshpande, S G; Bajaj, A N; Nikam, V S

    2015-12-01

    Colonic drug delivery is intended not only for local treatment in inflammatory bowel disease (IBD) but also for systemic delivery of therapeutics. Intestinal myeloperoxidase (MPO) determination could be used to estimate the average level of inflammation in colon as well as to determine the efficacy of drugs to be used in the treatment of inflammatory bowel diseases or study the specificity of dosage forms to be used for colonic targeting of anti-inflammatory drugs. Colonic prodrug sulfasalazine (SASP) gets metabolized to give 5-aminosalicylic acid (5-ASA), which is the active portion of SASP. However, when given orally, 5-ASA is absorbed in upper part of gastrointestinal tract (GIT) and not made available in colon. In the present study, colon-targeted delivery of 5-ASA was achieved by formulating tablets with two natural polymers namely guar gum and pectin using compression coating method. Colonic specificity of 5-ASA tablets (prepared using guar gum and pectin as polymers) was evaluated in vitro using simulated fluids mimicking in vivo environment as well as in vivo method using chemically (2,4,6-trinitrobenzenesulfonic acid and acetic acid)-induced colitis rat model. Both colon-specific formulations of 5-ASA (guar gum and pectin) were observed to be more effective in reducing inflammation in chemically induced colitis rat models when compared to colon-specific prodrug sulfasalazine as well as conventional 5-ASA administered orally. PMID:26017284

  10. In Vivo Evaluation of 5-ASA Colon-Specific Tablets Using Experimental-Induced Colitis Rat Animal Model.

    PubMed

    Sawarkar, Sujata P; Deshpande, S G; Bajaj, A N; Nikam, V S

    2015-12-01

    Colonic drug delivery is intended not only for local treatment in inflammatory bowel disease (IBD) but also for systemic delivery of therapeutics. Intestinal myeloperoxidase (MPO) determination could be used to estimate the average level of inflammation in colon as well as to determine the efficacy of drugs to be used in the treatment of inflammatory bowel diseases or study the specificity of dosage forms to be used for colonic targeting of anti-inflammatory drugs. Colonic prodrug sulfasalazine (SASP) gets metabolized to give 5-aminosalicylic acid (5-ASA), which is the active portion of SASP. However, when given orally, 5-ASA is absorbed in upper part of gastrointestinal tract (GIT) and not made available in colon. In the present study, colon-targeted delivery of 5-ASA was achieved by formulating tablets with two natural polymers namely guar gum and pectin using compression coating method. Colonic specificity of 5-ASA tablets (prepared using guar gum and pectin as polymers) was evaluated in vitro using simulated fluids mimicking in vivo environment as well as in vivo method using chemically (2,4,6-trinitrobenzenesulfonic acid and acetic acid)-induced colitis rat model. Both colon-specific formulations of 5-ASA (guar gum and pectin) were observed to be more effective in reducing inflammation in chemically induced colitis rat models when compared to colon-specific prodrug sulfasalazine as well as conventional 5-ASA administered orally.

  11. Intestinal anti-inflammatory activity of calcium pyruvate in the TNBS model of rat colitis: Comparison with ethyl pyruvate.

    PubMed

    Algieri, F; Rodriguez-Nogales, A; Garrido-Mesa, J; Camuesco, D; Vezza, T; Garrido-Mesa, N; Utrilla, P; Rodriguez-Cabezas, M E; Pischel, I; Galvez, J

    2016-03-01

    Pyruvate is a key intermediate of the carbohydrate metabolism with endogenous scavenger properties. However, it cannot be used in clinics due to its instability. Ethyl pyruvate (EP) has shown better stability as well as an antioxidant and anti-inflammatory activity. Calcium pyruvate monohydrate (CPM) is another stable pyruvate derivative that could also provide the benefits from calcium, fundamental for bone health. Considering everything, we propose CPM as a therapeutic strategy to treat diseases with an immune component in which there is also a significant dysregulation of the skeletal homeostasis. This could be applicable to inflammatory bowel disease, which is characterized by over-production of pro-inflammatory mediators, including cytokines and reactive oxygen and nitrogen metabolites that induces intestinal mucosal damage and chronic inflammation, and extra-intestinal symptoms like osteopenia and osteoporosis. The effects of CPM and EP (20, 40 and 100mg/kg) were evaluated on the trinitrobenzenesulfonic acid (TNBS) model of colitis in rats, after a 7-day oral treatment, with main focus on colonic histology and inflammatory mediators. Both pyruvates showed intestinal anti-inflammatory effects in the TNBS-induced colitis. They were evident both histologically, with a recovery of the mucosal cytoarchitecture and a reduction of the neutrophil infiltration, and through the profile of inflammatory mediators (IL-1, IL-6, IL-17, IL-23, iNOS). However, CPM appeared to be more effective than ethyl pyruvate. In conclusion, CPM exerts intestinal anti-inflammatory effect on the TNBS-induced colitis in rats, although further experiments are needed to explore its beneficial effects on bone health and osteoporosis.

  12. Intestinal anti-inflammatory effects of oligosaccharides derived from lactulose in the trinitrobenzenesulfonic acid model of rat colitis.

    PubMed

    Algieri, Francesca; Rodríguez-Nogales, Alba; Garrido-Mesa, Natividad; Vezza, Teresa; Garrido-Mesa, José; Utrilla, M Pilar; Montilla, Antonia; Cardelle-Cobas, Alejandra; Olano, Agustín; Corzo, Nieves; Guerra-Hernández, Eduardo; Zarzuelo, Antonio; Rodriguez-Cabezas, M Elena; Galvez, Julio

    2014-05-14

    Intestinal microbiota modulation is becoming an interesting approach to manage inflammatory bowel disease and can be achieved by the administration of prebiotics. Previous studies showed the intestinal anti-inflammatory effects of the prebiotic lactulose. The aim of the present study was to test the preventative effects of oligosaccharides derived from lactulose with prebiotic properties (OsLu) in the trinitrobenzenesulfonic acid model of rat colitis and compare them with those of lactulose. Both treatments modified bacterial profile in intestinal contents, increasing the bifidobacteria and lactobacilli counts and up-regulating the production of short-chain fatty acids, although OsLu generated a larger amount. OsLu also inhibited to a greater extent different pro-inflammatory markers such as interleukins (IL) 1, 6, 12, and 23 and chemokines (MCP-1 and CINC-1). However, both prebiotics equally restored colonic epithelial integrity, evaluated both with a histological score (OsLu, 9.8 ± 2.2; and lactulose, 12.1 ± 2.1, vs colitic control, 27.3 ± 3.3) and by measuring several key proteins of the mucosal barrier (MUC-2, MUC-3, and TTF-3). OsLu effect was also associated with an inhibition of iNOS expression and a reduction of Th17 cell activity in the inflamed tissue that facilitated the intestinal mucosa barrier recovery. In conclusion, OsLu showed a better anti-inflammatory profile than lactulose in this model of experimental colitis.

  13. Apical leptin induces chloride secretion by intestinal epithelial cells and in a rat model of acute chemotherapy-induced colitis

    PubMed Central

    Hoda, Raschid M.; Scharl, Michael; Keely, Stephen J.; McCole, Declan F.

    2010-01-01

    The purpose of this study was to investigate whether luminal leptin alters ion transport properties of the intestinal epithelium under acute inflammatory conditions. Monolayers of human intestinal T84 epithelial cells and a rat model of chemotherapy-induced enterocolitis were used. Cells were treated with leptin and mounted in Ussing chambers to measure basal and secretagogue-induced changes in transepithelial short-circuit current (Isc). Furthermore, the role of MAPK and phosphatidylinositol 3-kinase (PI3K) signaling pathways in mediating responses to leptin was investigated. Acute colitis in Sprague-Dawley rats was induced by intraperitoneal injection of 40 mg/kg methotrexate. Leptin (100 ng/ml) induced a time-dependent increase in basal Isc in T84 intestinal epithelial cells (P < 0.01). Moreover, pretreatment of T84 cells with leptin for up to 1 h significantly potentiated carbachol- and forskolin-induced increases in Isc. Pretreatment with an inhibitor of MAPK abolished the effect of leptin on basal, carbachol- and forskolin-induced chloride secretion (P < 0.05). However, the PI3K inhibitor, wortmannin, only blunted the effect of leptin on forskolin-induced increases in Isc. Furthermore, leptin treatment evoked both ERK1/2 and Akt1 phosphorylation in T84 cells. In the rat model, luminal leptin induced significant increases in Isc across segments of proximal and, to a lesser extent, distal colon (P < 0.05). We conclude that luminal leptin is likely an intestinal chloride secretagogue, particularly when present at elevated concentrations and/or in the setting of inflammation. Our findings may provide a mechanistic explanation, at least in part, for the clinical condition of secretory diarrhea both in hyperleptinemic obese patients and in patients with chemotherapy-induced intestinal inflammation. PMID:20203064

  14. Oral Feeding of Probiotic Bifidobacterium infantis: Colonic Morphological Changes in Rat Model of TNBS-Induced Colitis.

    PubMed

    Javed, Najma H; Alsahly, Musaad B; Khubchandani, Jagdish

    2016-01-01

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. It has been proposed that modifying the bacterial flora in intestine with probiotics may decrease the inflammatory process and prevent relapses in UC. We investigated the possible protective and therapeutic effects of a single strand of probiotic, Bifidobacterium infantis (BI), on colonic inflammation, in rats with regular feedings. Two groups of Lewis rats were prepared (n = 8). The first group was the control, sham-fed group (n = 4). The other group was the experimental BI-fed group (n = 4). Colitis was induced in both groups by intrarectal administration of TNBS under light anesthesia. The sham-fed colitis induced groups received a daily oral gavage feeding of 1.0 mL distilled water, whereas the B. infantis-fed group received 0.205 g of B. infantis dissolved in 1.0 mL distilled water daily. The change in body weight and food and water intake was recorded over the course of each study and analyzed. The rats were euthanized and tissues from the descending colon were harvested and analyzed microscopically and histologically. Results of our study indicated significant reduction in inflammation, mucosal damage, and preservation of goblet cells, as compared to the control animals. Modulation of gastrointestinal (GI) flora suggests a promising field in developing strategies for prevention and treatment of inflammatory bowel diseases by dietary modifications. PMID:27127686

  15. Oral Feeding of Probiotic Bifidobacterium infantis: Colonic Morphological Changes in Rat Model of TNBS-Induced Colitis

    PubMed Central

    Javed, Najma H.; Alsahly, Musaad B.; Khubchandani, Jagdish

    2016-01-01

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. It has been proposed that modifying the bacterial flora in intestine with probiotics may decrease the inflammatory process and prevent relapses in UC. We investigated the possible protective and therapeutic effects of a single strand of probiotic, Bifidobacterium infantis (BI), on colonic inflammation, in rats with regular feedings. Two groups of Lewis rats were prepared (n = 8). The first group was the control, sham-fed group (n = 4). The other group was the experimental BI-fed group (n = 4). Colitis was induced in both groups by intrarectal administration of TNBS under light anesthesia. The sham-fed colitis induced groups received a daily oral gavage feeding of 1.0 mL distilled water, whereas the B. infantis-fed group received 0.205 g of B. infantis dissolved in 1.0 mL distilled water daily. The change in body weight and food and water intake was recorded over the course of each study and analyzed. The rats were euthanized and tissues from the descending colon were harvested and analyzed microscopically and histologically. Results of our study indicated significant reduction in inflammation, mucosal damage, and preservation of goblet cells, as compared to the control animals. Modulation of gastrointestinal (GI) flora suggests a promising field in developing strategies for prevention and treatment of inflammatory bowel diseases by dietary modifications. PMID:27127686

  16. Resveratrol Pretreatment Ameliorates TNBS Colitis in Rats

    PubMed Central

    Yildiz, Gulserap; Yildiz, Yuksel; Ulutas, Pinar A.; Yaylali, Aslı; Ural, Muruvvet

    2015-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease in humans constituting a major health concern today whose prevalence has been increasing over the world. Production of reactive oxygen species (ROS) and disturbed capacity of antioxidant defense in IBD subjects have been reported. Antioxidants may play a significant role in IBD treatment. This study aimed at evaluating ameliorative effects of intraperitoneal resveratrol pretreatment on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Thirty five Wistar-Albino female rats were divided equally into five groups. Inflammation was induced by the intrarectal administration of TNBS under anesthesia. Intraperitoneal administration of resveratrol (RSV) at a concentration of 10mg/kg/day for 5 days before the induction of colitis significantly reduced microscopy score and malondialdehyde (MDA) levels and increased glutathione peroxidase (GSH Px) activity compared to TNBS and vehicle groups. Also an insignificant increase in catalase (CAT) activity was observed in the RSV treated group compared to TNBS and vehicle groups. In this paper, the most recent patent on the identification and treatment of IBD was indicated. In conclusion, antioxidant RSV proved to have a beneficial effect on TNBS colitis in rats. In light of these advantageous results, the RSV can be considered as adjuvant agent in IBD treatments. PMID:26246013

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

    PubMed

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

    2016-01-01

    We investigated the probiotic potential of lactic acid bacteria (LAB) obtained from cocoa fermentation using an experimental rat model of colitis. Cocoa beans were collected from fermentation boxes every 12 h for 5 days to isolate the microorganisms. Strains were isolated by serial dilution and plating on MRS agar. Gram-positive and catalase-negative rods were subjected to DNA extraction, polymerase chain reaction, and sequencing. Ten strains were randomly pooled and used to prepare a fermented milk drink that was used to treat the experimental colitis. A parallel group was treated with a single strain drink. Serum concentrations of cytokines and IgA, total and differential counts of blood leukocytes, and histological appearance were compared with the untreated control colitis group. Eighty strains of LAB were identified as Lactobacillus fermentum (68) and Lactobacillus plantarum (12). The multi-strain LAB pool significantly reduced the total number of leukocytes. There was a significant reduction in the percentage of neutrophils and monocytes compared with the control colitis group. IFN-γ concentration was downregulated in animals treated with the LAB pool. IL-10 and IgA increased significantly in the group treated with the strains. Histological analysis showed that the LAB pool reduced the inflammatory infiltrate and restored tissue architecture. The group treated with the single strain LAB drink (L. fermentum) showed no signs of inflammation remission. The results confirm the probiotic action of cocoa-derived LAB in the treatment of experimental colitis. Studies using isogenic models and humans will clarify the mechanisms of immune response modulation in inflammatory bowel disease. PMID:27525878

  18. Pretreatment with the probiotic VSL#3 delays transition from inflammation to dysplasia in a rat model of colitis-associated cancer.

    PubMed

    Appleyard, Caroline B; Cruz, Myrella L; Isidro, Angel A; Arthur, Janelle C; Jobin, Christian; De Simone, Claudio

    2011-12-01

    Evidence supports involvement of microflora in the transition of chronic inflammation to neoplasia. We investigated the protective efficacy of the probiotic VSL#3 in a model of colitis-associated colorectal cancer. Chronic colitis was induced in Sprague-Dawley rats by administration of trinitrobenzene sulfonic acid (TNBS), followed 6 wk later by systemic reactivation. To induce colitis-associated dysplasia and cancer, the animals received TNBS (intravenously) twice a week for 10 wk. One group received VSL#3 in drinking water from 1 wk before colitis induction until death. The colons were examined for damage and presence of dysplasia or cancer. Samples were analyzed for cell proliferation and apoptosis, vitamin D receptor (VDR) expression, angiogenic factors, and presence of alkaline sphingomyelinase or phosphatase. Microbial community composition was evaluated by terminal restriction fragment-length polymorphism analysis of the bacterial 16S rRNA gene. None of the probiotic-treated animals developed carcinoma, and no high-grade dysplasia was found in either the proximal or mid colon. In contrast, 29% of the animals in the control group developed carcinoma in one or more regions of the colon. VSL#3-treated animals had significantly less damage than the vehicle treated-controls in all areas of the colon, and this correlated with decreased richness and diversity of the mucosally adherent microbiota. Treatment with the probiotic increased the antiangiogenic factor angiostatin, VDR expression, and alkaline sphingomyelinase. We concluded that pretreatment with the probiotic VSL#3 can attenuate various inflammatory-associated parameters, delaying transition to dysplasia and cancer, thus offering its potential therapeutic use in patients with long-standing colitis. PMID:21903764

  19. The effect of methylsulfonylmethane on the experimental colitis in the rat

    SciTech Connect

    Amirshahrokhi, K.; Bohlooli, S.; Chinifroush, M.M.

    2011-06-15

    Methylsulfonylmethane (MSM), naturally occurring in green plants, fruits and vegetables, has been shown to exert anti-inflammatory and antioxidant effects. MSM is an organosulfur compound and a normal oxidative metabolite of dimethyl sulfoxide. This study was carried out to investigate the effect of MSM in a rat model of experimental colitis. Colitis was induced by intracolonic instillation of 1 ml of 5% of acetic acid. Rats were treated with MSM (400 mg/kg/day, orally) for 4 days. Animals were euthanized and distal colon evaluated histologically and biochemically. Tissue samples were used to measurement of malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), glutathione (GSH) and proinflammatory cytokine (TNF-{alpha} and IL-1{beta}) levels. Results showed that MSM decreased macroscopic and microscopic colonic damage scores caused by administration of acetic acid. MSM treatment also significantly reduced colonic levels of MDA, MPO and IL-1{beta}, while increased the levels of GSH and CAT compared with acetic acid-induced colitis group. It seems that MSM as a natural product may have a protective effect in an experimental ulcerative colitis. - Research Highlights: > Methylsulfonylmethane occurs naturally in some green plants, fruits and vegetables. > Methylsulfonylmethane (MSM) has anti-inflammatory and antioxidant effects. > We evaluated the effects of MSM in a rat model of experimental ulcerative colitis. > MSM has protective effect against acetic acid-induced colitis in rat.

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

    PubMed

    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. PMID:27378376

  1. Actions of Probiotics on Trinitrobenzenesulfonic Acid-Induced Colitis in Rats

    PubMed Central

    Shiina, Takahiko; Shima, Takeshi; Naitou, Kiyotada; Nakamori, Hiroyuki; Sano, Yuuki; Horii, Kazuhiro; Shimakawa, Masaki; Ohno, Hiroshi; Shimizu, Yasutake

    2015-01-01

    We investigated the actions of probiotics, Streptococcus faecalis 129 BIO 3B (SF3B), in a trinitrobenzenesulfonic acid- (TNBS-) induced colitis model in rats. After TNBS was administered into the colons of rats for induction of colitis, the rats were divided into two groups: one group was given a control diet and the other group was given a diet containing SF3B for 14 days. There were no apparent differences in body weight, diarrhea period, macroscopic colitis score, and colonic weight/length ratio between the control group and SF3B group, suggesting that induction of colitis was not prevented by SF3B. Next, we investigated whether SF3B-containing diet intake affects the restoration of enteric neurotransmissions being damaged during induction of colitis by TNBS using isolated colonic preparations. Recovery of the nitrergic component was greater in the SF3B group than in the control group. A compensatory appearance of nontachykininergic and noncholinergic excitatory components was less in the SF3B group than in the control group. In conclusion, the present study suggests that SF3B-containing diet intake can partially prevent disruptions of enteric neurotransmissions induced after onset of TNBS-induced colitis, suggesting that SF3B has therapeutic potential. PMID:26550572

  2. Effect of venlafaxine on experimental colitis in normal and reserpinised depressed rats

    PubMed Central

    Minaiyan, Mohsen; Hajhashemi, Valiollah; Rabbani, Mohammad; Fattahian, Ehsan; Mahzouni, Parvin

    2015-01-01

    Psychological disorders such as depression have more prevalence in inflammatory bowel disease patients and can exacerbate the clinical course of the disease, so anti-depressant therapy may have a potential to positively impact the disease course. On the other hand several antidepressant drugs have shown anti-inflammatory and immunomodulatory properties. Thus, this study aimed to explore the beneficial effects of venlafaxine on experimental colitis in normal and reserpinised depressed rats. Acetic acid colitis was induced in both reserpinised and non-reserpinised rats. Reserpinised groups received reserpine at dose of 6 mg/kg i.p.1 h prior to colitis induction and then treated with venlafaxine at doses of 10, 20, 40 mg/kg given i.p. 2 h after induction of colitis and daily for 4 consecutive days. Non-reserpinised groups treated with 10, 20, 40 mg/kg venlafaxine i.p. 2 h after the induction of colitis and daily for 4 successive days. Dexamethasone (1 mg/kg, i.p.) was used as reference drug. Colonic inflammation was evaluated using macroscopic, histological and myeloperoxidase activity measurements. Results showed that reserpine at dose of 6 mg/kg exacerbated the colitis damage. Compared to acetic acid control, venlafaxine at dose of 40 mg/kg as well as dexamethasone significantly improved colitis parameters in both reserpinised and non-reserpinised animals. Venlafaxine reduced inflammatory injury in this animal model of induced ulcerative colitis. These effects are probably mediated first through depressive behavioral changes that could be mediated through the brain-gut axis and second for the anti-inflammatory effect of the drug. PMID:26600857

  3. Protective Effect of Ocimum basilicum Essential Oil Against Acetic Acid-Induced Colitis in Rats.

    PubMed

    Rashidian, Amir; Roohi, Parnia; Mehrzadi, Saeed; Ghannadi, Ali Reza; Minaiyan, Mohsen

    2016-10-01

    Ocimum basilicum L has been traditionally used for the treatment of inflammatory bowel disease in Iran. This study investigates the ameliorative effect of Ocimum basilicum essential oil on an acetic acid-induced colitis model in rats. Ocimum basilicum essential oil with 2 doses (200 and 400 μL/kg) significantly ameliorated wet weight/length ratio of colonic tissue compared to the control group. Higher doses of essential oil (200 and 400 μL/kg) significantly reduced ulcer severity, ulcer area, and ulcer index. On the other hand, histological examination revealed the diminution of total colitis index as a marker for inflammatory cell infiltration in the colonic segments of rats treated with Ocimum basilicum essential oil (200 and 400 μL/kg). The increased level of myeloperoxidase was significantly decreased after the treatment with the essential oil (200 and 400 μL/kg). These results suggest that Ocimum basilicum exhibits protective effect against acetic acid-induced colitis.

  4. Dextran Sulfate Sodium (DSS)-Induced Acute Colitis in the Rat.

    PubMed

    Martin, Jérôme C; Bériou, Gaëlle; Josien, Régis

    2016-01-01

    Inflammatory bowel diseases (IBDs) are complex multifactorial disease thought to result from inappropriate immune responses to the gut microbiota, in genetically susceptible individuals, under the influence of environmental factors. Among the different animal models developed to help in understanding IBDs pathophysiological mechanisms as well as to achieve pharmacological preclinical studies, the dextran sulfate sodium (DSS)-induced colitis model is the most widely used because of its simplicity, cost-effectiveness, and similarity with human IBDs. This section provides with a detailed protocol that we validated in our laboratory to perform DSS-induced acute colitis in the Sprague-Dawley (SPD) rat.

  5. Dietary intervention with green dwarf banana flour (Musa sp AAA) prevents intestinal inflammation in a trinitrobenzenesulfonic acid model of rat colitis.

    PubMed

    Scarminio, Viviane; Fruet, Andrea C; Witaicenis, Aline; Rall, Vera L M; Di Stasi, Luiz C

    2012-03-01

    Dietary products are among the therapeutic approaches used to modify intestinal microflora and to promote protective effects during the intestinal inflammatory process. Because the banana plant is rich in resistant starch, which is used by colonic microbiota for the anaerobic production of the short-chain fatty acids that serve as a major fuel source for colonocytes: first, green dwarf banana flour produces protective effects on the intestinal inflammation acting as a prebiotic and, second, combination of this dietary supplementation with prednisolone presents synergistic effects. For this, we used the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. Our results revealed that the protective effect produced by a combination of 10% green dwarf banana flour with prednisolone was more pronounced than those promoted by a single administration of prednisolone or a diet containing 10% or 20% banana flour. This beneficial effect was associated with an improvement in the colonic oxidative status because the banana flour diet prevented the glutathione depletion and inhibited myeloperoxidase activity and lipid peroxidation. In addition, the intestinal anti-inflammatory activity was associated with an inhibition of alkaline phosphatase activity, a reduction in macroscopic and microscopic scores, and an extension of the lesions. In conclusion, the dietary use of the green dwarf banana flour constitutes an important dietary supplement and complementary medicine product to prevention and treatment of human inflammatory bowel disease.

  6. Relevance of TNBS-Colitis in Rats: A Methodological Study with Endoscopic, Histologic and Transcriptomic Characterization and Correlation to IBD

    PubMed Central

    Brenna, Øystein; Furnes, Marianne W.; Drozdov, Ignat; van Beelen Granlund, Atle; Flatberg, Arnar; Sandvik, Arne K.; Zwiggelaar, Rosalie T. M.; Mårvik, Ronald; Nordrum, Ivar S.; Kidd, Mark; Gustafsson, Björn I.

    2013-01-01

    Background Rectal instillation of trinitrobenzene sulphonic acid (TNBS) in ethanol is an established model for inflammatory bowel disease (IBD). We aimed to 1) set up a TNBS-colitis protocol resulting in an endoscopic and histologic picture resembling IBD, 2) study the correlation between endoscopic, histologic and gene expression alterations at different time points after colitis induction, and 3) compare rat and human IBD mucosal transcriptomic data to evaluate whether TNBS-colitis is an appropriate model of IBD. Methodology/Principal Findings Five female Sprague Daley rats received TNBS diluted in 50% ethanol (18 mg/0.6 ml) rectally. The rats underwent colonoscopy with biopsy at different time points. RNA was extracted from rat biopsies and microarray was performed. PCR and in situ hybridization (ISH) were done for validation of microarray results. Rat microarray profiles were compared to human IBD expression profiles (25 ulcerative colitis Endoscopic score demonstrated mild to moderate colitis after three and seven days, but declined after twelve days. Histologic changes corresponded with the endoscopic appearance. Over-represented Gene Ontology Biological Processes included: Cell Adhesion, Immune Response, Lipid Metabolic Process, and Tissue Regeneration. IL-1α, IL-1β, TLR2, TLR4, PRNP were all significantly up-regulated, while PPARγ was significantly down-regulated. Among genes with highest fold change (FC) were SPINK4, LBP, ADA, RETNLB and IL-1α. The highest concordance in differential expression between TNBS and IBD transcriptomes was three days after colitis induction. ISH and PCR results corresponded with the microarray data. The most concordantly expressed biologically relevant pathways included TNF signaling, Cell junction organization, and Interleukin-1 processing. Conclusions/Significance Endoscopy with biopsies in TNBS-colitis is useful to follow temporal changes of inflammation visually and histologically, and to acquire tissue for gene

  7. Xilei San Ameliorates Experimental Colitis in Rats by Selectively Degrading Proinflammatory Mediators and Promoting Mucosal Repair

    PubMed Central

    Hori, Kazutoshi; Wang, Shenglan; Kogure, Yoko; Fukunaga, Ken; Kashiwamura, Shinichiro; Yamamoto, Satoshi; Nakamura, Shiro; Li, Junxiang; Miwa, Hiroto; Noguchi, Koichi

    2014-01-01

    Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC. PMID:25120575

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

    PubMed Central

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

    2016-01-01

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

  9. Effect of Manuka honey and sulfasalazine in combination to promote antioxidant defense system in experimentally induced ulcerative colitis model in rats.

    PubMed

    Medhi, B; Prakash, A; Avti, P K; Saikia, U N; Pandhi, P; Khanduja, K L

    2008-08-01

    Manuka honey (MH, 5g/kg) provided protection against trinitro-benzo-sulphonic acid induced colonic damage. Combination therapy (MH+sulfasalazine) also reduced colonic inflammation and all the biochemical parameters were significant compared to control and MH alone treated group. Combination therapy showed additive effect of the MH which restored lipid peroxidation and improvement of antioxidant parameters. Morphological and histological scores were significantly reduced in combination groups. In inflammatory model of colitis, oral administration of MH (5g/kg) and combination with sulfasalazine (360 mg/kg) with MH (5g/kg) significantly reduced the colonic inflammation. The results indicate the additive effect of Manuka honey with sulfasalazine in colitis.

  10. Therapeutic efficacy and mechanism of Zhenrenyangzang decoction in rats with experimental ulcerative colitis

    PubMed Central

    Wang, Hui; Li, Shu-Hua; Zhang, Yan; Guan, Jie; Wu, Yan-Min; Wang, Qi; Luo, Xiao-Qing

    2015-01-01

    Zhenrenyangzang Decoction (ZD) has been used as a classic formula in China for the treatment of gastrointestinal dysfunction such as chronic gastritis. However, there is less study on its application in ulcerative colitis (UC) and the effects are not yet clearly defined. To explore the effectiveness of ZD in trinitrobenzene sulfonic acid (TNBS)-induced UC rats, ZD was administered orally for 8 days at a dosage of 2, 4 or 8 g/kg/day. Following drug administration, the disease activity index (DAI) and tissue damage scores were recorded. In addition, mRNA and protein expression of nuclear factor kappa B (NF-κB), p38 mitogen activated protein kinase (p38MAPK) and Toll-like receptor 2 (TLR2) in colon tissues were examined by real time PCR and western blotting assay. As compared with the UC model group, ZD promoted the recovery of colitis and inhibited the colonic inflammation damage in UC rats by reducing the mRNA or protein expression of NF-κB and p38MAPK, as well as activating the production of TLR2 in colon tissues. And ZD significantly reduced the DAI and tissue damage scores. The therapeutic effect of ZD was found to be comparable to that of SASP. Our results suggested that ZD could improve colonic mucosa impairment and possesses favorable therapeutic action in TNBS-induced colitis, which provides direct pharmacological evidence for its clinical application. PMID:26629011

  11. Protective Effect of Ocimum basilicum Essential Oil Against Acetic Acid-Induced Colitis in Rats.

    PubMed

    Rashidian, Amir; Roohi, Parnia; Mehrzadi, Saeed; Ghannadi, Ali Reza; Minaiyan, Mohsen

    2016-10-01

    Ocimum basilicum L has been traditionally used for the treatment of inflammatory bowel disease in Iran. This study investigates the ameliorative effect of Ocimum basilicum essential oil on an acetic acid-induced colitis model in rats. Ocimum basilicum essential oil with 2 doses (200 and 400 μL/kg) significantly ameliorated wet weight/length ratio of colonic tissue compared to the control group. Higher doses of essential oil (200 and 400 μL/kg) significantly reduced ulcer severity, ulcer area, and ulcer index. On the other hand, histological examination revealed the diminution of total colitis index as a marker for inflammatory cell infiltration in the colonic segments of rats treated with Ocimum basilicum essential oil (200 and 400 μL/kg). The increased level of myeloperoxidase was significantly decreased after the treatment with the essential oil (200 and 400 μL/kg). These results suggest that Ocimum basilicum exhibits protective effect against acetic acid-induced colitis. PMID:26620574

  12. Prostaglandin ethanolamides attenuate damage in a human explant colitis model.

    PubMed

    Nicotra, Lauren L; Vu, Megan; Harvey, Benjamin S; Smid, Scott D

    2013-01-01

    Endocannabinoids are protective in animal colitis models. As endocannabinoids also form novel prostaglandin ethanolamides (prostamides) via COX-2, we investigated the effects of prostamides and other COX-2 mediators on tissue damage in an ex vivo human mucosal explant colitis model. Healthy human colonic mucosae were incubated with pro-inflammatory cytokines TNF-α and IL-1β to elicit colitis-like tissue damage. The PGF-ethanolamide analogue, bimatoprost decreased colitis scores which were reversed by a prostamide-specific antagonist AGN 211334, but not the FP receptor antagonist AL-8810. PGF-ethanolamide and PGE-ethanolamide also reduced cytokine-evoked epithelial damage. Anandamide was protective in the explant colitis model; however COX-2 inhibition did not alter its effects, associated with a lack of COX-2 induction in explant mucosal tissue. These findings support an anti-inflammatory role for prostamides and endocannabinoids in the human colon. PMID:23380599

  13. The effects of LED rectal irradiation on the experimental ulcerative colitis in rats

    NASA Astrophysics Data System (ADS)

    Zeng, Chang-Chun; Wang, Xian-Ju; Guo, Zhou-Yi; Liu, Song-Hao

    2006-01-01

    We evaluated the effects of light emitting diode(LED λ 632.8nm; power 4.0mw)applied directly to the colon on the experimental ulcerative colitis. 34 rats were divided into 3 groups, which was LED treatment group (n=12), model group (n=12), and normal control group (n=10). Given glacial acetic acid (5%) intra-anally so as to be replicated the rat model of ulcerative colitis. LED irradiation was used to curative group, with 30min each time, once per day. The period of treatment was one week. Then the activity of superoxide dismutase (SOD) and content of malondi-aldehyde (MDA) in the blood plasma were detected and the histopathological study in Colonic tissue was performed. The degree of the Colonic tissue injury in curative group was not as significant as that in the model group. Comparing with model group, the Content of MDA in LED curative group was reductive and the activity of SOD was increased significantly. We concluded that the LED irradiation can protect colonic mucosa from acetic acid induced damage in rats and the effects may be related to the photobiomodulation of LED.

  14. Pelvic organ cross-sensitization to enhance bladder and urethral pain behaviors in rats with experimental colitis.

    PubMed

    Yoshikawa, S; Kawamorita, N; Oguchi, T; Funahashi, Y; Tyagi, P; Chancellor, M B; Yoshimura, N

    2015-01-22

    Neural cross-sensitization has been postulated as a mechanism underlying overlaps of chronic pelvic pain disorders such as bladder pain syndrome/interstitial cystitis (BPS/IC) and irritable bowel syndrome (IBS). Animals with experimental colitis have been used to study the underlying mechanisms for overlapped pelvic pain symptoms, and shown to exhibit bladder overactivity evidenced by frequent voiding; however, it has not directly been evaluated whether pain sensation derived from the lower urinary tract is enhanced in colitis models. Also, the cross-sensitization between the colon and urethra has not been studied previously. In the present study, we therefore investigated pain behaviors induced by nociceptive stimuli in the lower urinary tract and the involvement of C-fiber afferent pathways using rats with colitis induced by intracolonic application of 2,4,6-trinitrobenzenesulfonic acid (TNBS). In TNBS-induced colitis rats at 10 days, intravesical application of resiniferatoxin (RTx) induced a significantly greater number of episodes of both licking and freezing behaviors, which were reduced by capsaicin-sensitive C-fiber afferent desensitization. Histochemical studies using fluorescent dye tracers injected into the colon, bladder or urethra showed that dichotomized afferent neurons comprised 6.9-14.5% of L1, L6 and S1 dorsal root ganglion (DRG) neurons innervating the colon or the lower urinary tract. Transient receptor potential vanilloid 1 (TRPV1) mRNA expression was significantly increased in, the bladder, urethra and S1 DRG in colitis rats. An increase in myeloperoxidase (MPO) activity was found in the colon, but not in the bladder or urethra after intracolonic TNBS treatment. These results indicate that TNBS-induced colitis increased pain sensitivity in the bladder and urethra via activation of C-fiber afferent pathways due to colon-to-bladder and colon-to-urethral cross-sensitization, suggesting the contribution of pelvic organ cross

  15. The bisphosphonate alendronate improves the damage associated with trinitrobenzenesulfonic acid-induced colitis in rats

    PubMed Central

    Ballester, I; Daddaoua, A; López-Posadas, R; Nieto, A; Suárez, M D; Zarzuelo, A; Martínez-Augustin, O; de Medina, F Sánchez

    2007-01-01

    Background and purpose: The nitrogen-containing bisphosphonates are drugs used successfully in the treatment of osteoporosis. They act inhibiting farnesyl diphosphate synthase. This mechanism may also produce anti-inflammatory effects. The therapeutic activity of alendronate was tested in vivo using a model of inflammatory bowel disease. Experimental approach: The trinitrobenzenesulfonic acid model of colitis in the rat was used. Rats were treated orally with alendronate and its efficacy compared with that of oral sulphasalazine or vehicle, starting 2 h after colitis induction. The status of the animals was assessed 5 days later. Key results: Alendronate treatment (25 or 75 mg kg-1 day-1) resulted in a decrease in the colonic damage score and loss of body weight (at 25 mg kg-1 day-1 only). This was associated to a dramatic reduction in the mRNA levels of interleukin 1β (IL-1β), monocyte chemoattractant protein 1 (MCP-1) and interleukin 1 receptor antagonist (IL-1ra). The magnitude of the beneficial effect was comparable to that of sulphasalazine (at a 6-20 fold higher dose). Thus sulphasalazine post-treatment reduced the mRNA levels of IL-1β/IL-1ra and MCP-1 to the same extent as alendronate and additionally lowered colonic alkaline phosphatase activity, but failed to affect body weight loss or colonic damage score. Alendronate failed to exert beneficial effects when administered intraperitoneally. Conclusions and Implications: Oral but not intraperitoneal alendronate significantly protected the colon in experimental rat colitis. Inflammatory bowel disease patients might benefit from exposure to oral alendronate. PMID:17375077

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

    PubMed

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Kuśnierz-Cabala, Beata; Konturek, Peter; Ambroży, Tadeusz; Dembiński, Artur

    2016-01-01

    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.

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

    PubMed

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

    2016-01-01

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

  18. Effects of mimic of manganese superoxide dismutase on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats.

    PubMed

    Wang, Yan-Hong; Dong, Jiao; Zhang, Jian-Xin; Zhai, Jing; Ge, Bin

    2016-09-01

    The mimic of manganese superoxide dismutase (MnSODm) has been synthesized and reported to have anti-inflammatory properties. However, whether MnSODm has anti-inflammatory effects on colitis and any underlying mechanisms are poorly understood. This study was to investigate therapeutic effects and mechanism of MnSODm on 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis model in rats. Rats were intragastrically administered MnSODm (10, 20, and 40 mg/kg) per day for 7 days after colitis was induced by TNBS. After treated with MnSODm, the colonic macroscopic and microscopic damage scores and colonic weight/length ratios were significantly decreased compared with colitis model group. Myeloperoxidase (MPO) activity, malonyldialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 levels in colon tissues were also significantly decreased in MnSODm treatment groups. However, superoxide dismutase (SOD) activity significantly increased and phosphorylated inhibitory kappa B-alpha (IκBα), inhibitor kappa B kinase (IKKα/β), and nuclear factor-kappa Bp65 (NF-κBp65) as well as Toll-like receptor 4 (TLR4) and myeloid differentiation actor 88 (MyD88) in the colonic mucosa were significantly inhibited by MnSODm treatment. Thus, MnSODm was protective against colitis via antioxidant activity and by inhibiting inflammatory mediators by down-regulating TLR4/MyD88/NF-κB signaling pathways. These data suggest a potential therapeutic effect of MnSODm in colitis.

  19. Effects of mimic of manganese superoxide dismutase on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats.

    PubMed

    Wang, Yan-Hong; Dong, Jiao; Zhang, Jian-Xin; Zhai, Jing; Ge, Bin

    2016-09-01

    The mimic of manganese superoxide dismutase (MnSODm) has been synthesized and reported to have anti-inflammatory properties. However, whether MnSODm has anti-inflammatory effects on colitis and any underlying mechanisms are poorly understood. This study was to investigate therapeutic effects and mechanism of MnSODm on 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis model in rats. Rats were intragastrically administered MnSODm (10, 20, and 40 mg/kg) per day for 7 days after colitis was induced by TNBS. After treated with MnSODm, the colonic macroscopic and microscopic damage scores and colonic weight/length ratios were significantly decreased compared with colitis model group. Myeloperoxidase (MPO) activity, malonyldialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 levels in colon tissues were also significantly decreased in MnSODm treatment groups. However, superoxide dismutase (SOD) activity significantly increased and phosphorylated inhibitory kappa B-alpha (IκBα), inhibitor kappa B kinase (IKKα/β), and nuclear factor-kappa Bp65 (NF-κBp65) as well as Toll-like receptor 4 (TLR4) and myeloid differentiation actor 88 (MyD88) in the colonic mucosa were significantly inhibited by MnSODm treatment. Thus, MnSODm was protective against colitis via antioxidant activity and by inhibiting inflammatory mediators by down-regulating TLR4/MyD88/NF-κB signaling pathways. These data suggest a potential therapeutic effect of MnSODm in colitis. PMID:27506642

  20. Impact of colonic mucosal lipoxin A4 synthesis capacity on healing in rats with dextran sodium sulfate-induced colitis.

    PubMed

    Ağış, Erol R; Savaş, Berna; Melli, Mehmet

    2015-09-01

    Ulcerative colitis is a chronic inflammatory disease of the colon. This study evaluates the role of colonic mucosal lipoxin A4 (LXA4) synthesis in an experimental rat model of dextran sodium sulfate (DSS)-induced colitis. Wistar rats were randomly assigned to four groups: healthy controls, DSS-induced colitis with no or vehicle therapy, misoprostol or 5-aminosalicylic acid (5-ASA) therapy groups. Disease severity and colonic mucosal LXA4 synthesis was assessed specifically during the acute phase (day 5), chronic phase (day 15) and healing phases (day 19). Both misoprostol and 5-ASA reduced histopathologic score during the acute phase and reduced disease activity score at the healing phase. In addition, misoprostol reduced histopathologic score and colon weight/length ratio during the healing phase. Only misoprostol therapy increased colonic mucosal LXA4 synthesis. Furthermore, LXA4 levels correlated negatively with disease progression (R=-0.953). Collectively, our findings suggest that misoprostol-induced LXA4 synthesis may be favorable for the healing of ulcerative colitis.

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

    PubMed Central

    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

  2. Anti-inflammatory effects of nesfatin-1 in rats with acetic acid - induced colitis and underlying mechanisms.

    PubMed

    Ozturk, C C; Oktay, S; Yuksel, M; Akakin, D; Yarat, A; Kasimay Cakir, O

    2015-10-01

    Mucosal balance impairment, bacterial over-proliferation, cytokines, inflammatory mediators are known as responsible for inflammatory bowel disease. Besides known anorexigenic, neuroprotective, and anti-apoptotic effects, the major effect of nesfatin-1 on colitis is unknown. Our aim was to investigate the possible anti-inflammatory effects of nesfatin-1 in acetic acid induced colitis model and potential underlying mechanisms. Male Spraque-Dawley rats were anesthetized by intraperitoneal ketamine (100 mg/kg) and chlorpromazine (0.75 mg/kg). For nesfatin-1 and antagonist applications some of the rats were intracerebroventricularly (i.c.v.) cannulated. In colitis group, intrarectally (i.r.) 4% acetic acid solution (1 ml) and 10 minutes later i.c.v. nesfatin-1 (0.05 μg/5 μl) or vehicle (5 μl) were administered. Treatments continued for 3 days. In control group, physiological saline solution was used intrarectally. To identify the underlying effective mechanism of nesfatin-1, rats were divided into 3 subgroups, 5 minutes following colitis induction; i.c.v. atosiban (oxytocin receptor antagonist), SHU9119 (melanocortin receptor antagonist) or GHSR-1a antagonist (ghrelin receptor antagonist) were administered, 5 minutes later nesfatin-1 was administered for 3 days. On the fourth day, rats were decapitated, and colon tissues were sampled. Macroscopic and microscopic damage scores of distal colon, and colonic tissue malondialdehyde, glutathione, myeloperoxidase, superoxide dismutase, catalase, luminol and lucigenin chemiluminescence measurements were analysed. The increased myeloperoxidase activity, malondialdehyde levels, luminol and lucigenin chemiluminescence measurements, macroscopic and microscopic damage scores with colitis induction (P < 0.05 - 0.001) were decreased with nesfatin-1 treatment (P < 0.05 - 0.001). Nesfatin-1 may show this effect by inhibiting neutrophil infiltration through tissues and by decreasing formation of free oxygen radicals. Atosiban and

  3. Beneficial effect of trimebutine and N-monodesmethyl trimebutine on trinitrobenzene sulfonic acid-induced colitis in rats.

    PubMed

    Chevalier, Eric; Pétoux, Francine; Chovet, Maria; Langlois, Annik

    2004-12-01

    The use of local anesthetics, such as lidocaine, has been proposed in the treatment of distal ulcerative colitis. Trimebutine maleate (TMB) displays a local anesthetic activity higher than that of lidocaine in rabbit corneal reflex. TMB and nor-TMB its main metabolite in human show similar affinity to that of bupivacaine toward sodium channel labeled by [3H]batrachotoxin and block sodium currents in sensory neurons from rat dorsal root ganglia. The aim of this study was to evaluate the effects of TMB and nor-TMB in comparison to lidocaine and bupivacaine in a rat model of acute colonic inflammation induced by trinitrobenzene sulfonic acid (TNBS). A single intracolonic instillation of TNBS (50 mg/kg dissolved in ethanol 30%) led to early plasma extravasation then macroscopic damage (hyperemia and necrosis), increased colonic weight and tissular MPO, a marker of neutrophilic infiltration. Local administration of TMB at dose of 3 to 60 mg/kg, 30 min before, 24 and 48 h after colitis induction, significantly reduced the severity of colitis. Nor-TMB (1, 3, 10, 30 mg/kg) as well as lidocaine (1, 3, 10 mg/kg) dose-dependently reduced colitis while bupivacaine at 10 mg/kg did not affect it significantly. In contrast systemic administration of TMB, nor-TMB and lidocaine at 10 mg/kg had no significant effect. Furthermore, local administration of TMB (30 mg/kg) and lidocaine (10 mg/kg) significantly reduced plasmatic extravasation. In conclusion, intracolonic treatment with TMB and nor-TMB improved acute experimental TNBS-induced colitis in rat and these effects could be explained by their local anesthetic activity. PMID:15531383

  4. The influence of LED rectal irradiation on IL-1α and IL-4 of experimental ulcerative colitis in rats

    NASA Astrophysics Data System (ADS)

    Zeng, Chang-Chun; Wang, Xian-Ju; Liu, Han-Ping; Guo, Zhou-Yi; Liu, Song-Hao

    2006-09-01

    Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. In this paper, the influence of IL-1α and IL-4 on the experimental ulcerative colitis by light emitting diode ( LED ) (λ: 632.8nm; power: 4.0mw) applied to colon directly were studied. Making 30 rats into 3 groups: LED curative group, model group, normal control group. There were 10 rats of each group. We used glacial acetic acid (5%) and trinitro-benzene-sulfonic acid (TNBS) (1%) intra-anally to replicate the rat model of ulcerative colitis. After a week treatment with administrating LED rectal irradiation to curative group, 30mm each time, once per day, the histopathological studies in colonic tissue were performed, and the expression and distribution of IL-lα and IL-4 in colonic tissues were investigated by immunohistochemical staining. The extent of the Colonic tissue injury in LED curative group was not as significant as that in the model group. Compared with model group, the content of MDA in LED curative group was reductived and the activity of SOD was increased significantly, and the expression and distribution of IL-lα in LED curative group was depressed significantly, however the expression and distribution of IL-4 in LED curative group was increased obviously. This results show that the LED rectal irradiation can protect colonic mucosa from the experimental ulcerative colitis in rats, and suggest that the effects may be related to the photobiomodulation and immunomodulation of LED.

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

    PubMed Central

    Chung, Ho-Lam; Yue, Grace Gar-Lee; To, Ka-Fai; Su, Ya-Lun; Huang, Yu; Ko, Wing-Hung

    2007-01-01

    AIM: To investigate the effect of Scutellariae Radix extract (SRE) on ulcerative colitis (UC) in rats induced by dextran-sulfate sodium (DSS). METHODS: Colitis was induced in male Sprague-Dawley (SD) rats (170-180 g) by 4% dextran sulfate sodium (DSS, wt/v; MW 54000) in drinking water for 8 d. The treated rats received 4% DSS and SRE orally (100 mg/kg per day). Control rats received either tap water or SRE only. Macroscopic assessment which included body weight changes, fecal occult blood and stool consistency were determined daily. At the appointed time, the rats were sacrificed and the entire colons were removed. The colon length and the myeloperoxidase (MPO) activity were measured. The severity of colitis was graded by morphological and histological assessments. The ion transport activity of the colonic mucosa was assessed by electrophysiological technique. RESULTS: Rats treated with oral administration of 4% DSS regularly developed clinical and macroscopic signs of colitis. Treatment with SRE relieved the symptoms, including the reduction in body weight, shortening and ulceration of the colon. Administration of SRE also significantly reduced the histological damage induced by DSS. Moreover, the ISC responses of the colonic mucosa to forskolin were suppressed after the induction of colitis. The stimulated ion transport activity of DSS-rats treated with SRE displayed significant improvement in the secretory responsiveness. CONCLUSION: SRE was effective in treating acute DSS-induced ulcerative colitis, as gauged by reduced clinical disease, improved macroscopic and histological damage scores, and enhanced recovery of normal colonic secretory function. PMID:17948935

  6. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

    PubMed Central

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-01-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis. PMID:27598133

  7. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    PubMed

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-01-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis. PMID:27598133

  8. A diet with lactosucrose supplementation ameliorates trinitrobenzene sulfonic acid-induced colitis in rats.

    PubMed

    Zhou, Yan; Ruan, Zheng; Zhou, Xiaoli; Huang, Xiaoliu; Li, Hua; Wang, Ling; Zhang, Cui; Liu, Shiqiang; Deng, Zeyuan; Wu, Guoyao; Yin, Yulong

    2015-01-01

    Chronic intestinal inflammation contributes to an increased risk of colon cancer. Lactosucrose (LS), a kind of functional trisaccharide, can modulate immunity and promote microbe growth. The aim of this study was to investigate the effect of LS on 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced colitis in rats. Rats were randomly divided into four treatment groups: the normal group, TNBS group, LS group, and salicylazosulfapyridine (SASP) group for five weeks. LS supplementation ameliorated TNBS-induced colitis. LS supplementation increased IL-10 production and suppressed the secretion of IL-12 in the colon, as compared to the TNBS group. LS decreased the production of TLR-2 protein and nuclear NF-κB p65 protein, as well as mRNA levels, as compared with colitic rats. These results indicate that chronic feeding of LS inhibited TNBS-induced chronic inflammation. LS has potential nutraceutical intervention to combat colitis.

  9. AOM/DSS Model of Colitis-Associated Cancer.

    PubMed

    Parang, Bobak; Barrett, Caitlyn W; Williams, Christopher S

    2016-01-01

    Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in particular, have enabled fast and efficient analysis of genetic and environmental modulators of CAC without the added requirement of time-intensive genetic crossings. Here we describe the Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) mouse model of inflammatory colorectal cancer.

  10. A study of the effects of Cydonia oblonga Miller (Quince) on TNBS-induced ulcerative colitis in rats.

    PubMed

    Minaiyan, M; Ghannadi, A; Etemad, M; Mahzouni, P

    2012-04-01

    Cydonia oblonga Miller (Quince) from Rosaceae family is a fruit tree cultivated in many countries mainly in Iran. This study was carried out to investigate the effect of quince juice (QJ) and quince hydroalcoholic extract (QHE) on ulcerative colitis (UC) induced by TNBS (trinitrobenzene sulfonic acid) in rats. Rats were grouped (n=6) and fasted for 36 h before colitis induction. TNBS was instilled into the colon with a hydroalcoholic carrier and then treatments were made for 5 days starting 6 h after colitis induction with different doses of QJ (200, 400, 800 mg/kg), QHE (200, 500 & 800 mg/kg) orally, QJ (400 mg/kg) and QHE (200 and 500 mg/kg) intraperitoneally. The colon tissue was removed and tissue damages were scored after macroscopic and histopathologic assessments. Albeit the examined doses of QJ and QHE were apparently effective to reduce the extent of UC lesions, only the greatest doses (500 and 800 mg/kg) resulted in significant alleviation. Weight/Length ratio as an illustrative of tissue inflammation and extravasation was also diminished with quince treatments while the results correlated with macroscopic and histopathologic evaluations. These data suggest that QJ and QHE were effective to diminish inflammation and ulcer indices in this murine model of acute colitis. Although QHE with different doses was effective in induced colitis, the dose and/or route of administration dependency was not confirmed. So quince fractions could be considered as a suitable anticolitic alternative, however further studies are needed to support this hypothesis for clinical setting. PMID:23181087

  11. Altered vasoactive intestinal peptides expression in irritable bowel syndrome patients and rats with trinitrobenzene sulfonic acid-induced colitis

    PubMed Central

    Del Valle-Pinero, Arseima Y; Sherwin, LeeAnne B; Anderson, Ethan M; Caudle, Robert M; Henderson, Wendy A

    2015-01-01

    AIM: To investigate the vasoactive intestinal peptides (VIP) expression in irritable bowel syndrome (IBS) and trinitrobenzene sulfonic acid (TNBS) induced colitis. METHODS: The VIP gene expression and protein plasma levels were measured in adult participants (45.8% male) who met Rome III criteria for IBS for longer than 6 mo and in a rat model of colitis as induced by TNBS. Plasma and colons were collected from naïve and inflamed rats. Markers assessing inflammation (i.e., weight changes and myeloperoxidase levels) were assessed on days 2, 7, 14 and 28 and compared to controls. Visceral hypersensitivity of the rats was assessed with colo-rectal distension and mechanical threshold testing on hind paws. IBS patients (n = 12) were age, gender, race, and BMI-matched with healthy controls (n = 12). Peripheral whole blood and plasma from fasting participants was collected and VIP plasma levels were assayed using a VIP peptide-enzyme immunoassay. Human gene expression of VIP was analyzed using a custom PCR array. RESULTS: TNBS induced colitis in the rats was confirmed with weight loss (13.7 ± 3.2 g) and increased myeloperoxidase activity. Visceral hypersensitivity to colo-rectal distension was increased in TNBS treated rats up to 21 d and resolved by day 28. Somatic hypersensitivity was also increased up to 14 d post TNBS induction of colitis. The expression of an inflammatory marker myeloperoxidase was significantly elevated in the intracellular granules of neutrophils in rat models following TNBS treatment compared to naïve rats. This confirmed the induction of inflammation in rats following TNBS treatment. VIP plasma concentration was significantly increased in rats following TNBS treatment as compared to naïve animals (P < 0.05). Likewise, the VIP gene expression from peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients when compared to controls (P < 0.00001; 95%CI). VIP plasma protein was not significantly different when compared with

  12. Colon Delivery of Budesonide Using Solid Dispersion in Dextran for the Treatment and Secondary Prevention of Ulcerative Colitis in Rat

    PubMed Central

    Varshosaz, Jaleh; Ahmadi, Fatemeh; Emami, Jaber; Tavakoli, Naser; Minaiyan, Mohsen; Mahzouni, Parvin; Dorkoosh, Farid

    2010-01-01

    Objectives: Ulcerative colitis is characterized by local inflammation. Targeting drugs directly to the site of injury has the benefit of lower adverse effects and more effective therapy. The aim of this study was colon targeted delivery of budesonide to deliver the major part of the drug to the colon. Methods: Matrix tablets of budesonide from solid dispersion of drug with dextran were prepared using different drug to polymer ratios and three molecular weights of dextran. The physical evaluation and drug release behavior were studied. In vivo efficacy of the selected formulation against acetic acid induced colitis in rats was evaluated and compared to the control (untreated) and references (mesalazine and budesonide suspensions) groups. Results: The results showed that solid dispersion of budesonide with dextran in the ratio of 1:7 using molecular weight (MW) of 10,000 dextran (SDT710) released 25% of the drug in the first 6 hours and 100% in caecal and colonic contents. It could target the drug to colon with improvement in some of the inflammatory signs of induced ulcerative colitis in rat. Treatment with SDT710 could improve not only the percent of involvement also macroscopic damage parameters. The macroscopic parameters included weight/length ratio of the colon, ulcer area, damage score, and ulcer index reduced in comparison to the control group and conventional suspension of budesonide; however, only weight/length ratio was significant. Conclusions: In the experimental model studied, the new colonic delivery system significantly improved the efficacy of budesonide in the weight/length ratio of the colon in induced colitis in rats. PMID:21566772

  13. Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism.

    PubMed

    Larrosa, Mar; González-Sarrías, Antonio; Yáñez-Gascón, María J; Selma, María V; Azorín-Ortuño, María; Toti, Simona; Tomás-Barberán, Francisco; Dolara, Piero; Espín, Juan Carlos

    2010-08-01

    Whether the beneficial effects of pomegranate are due to the ellagitannins or to their microbiota-derived urolithins is not known. Our objectives were to evaluate the effects of pomegranate intake and its main microbiota-derived metabolite urolithin-A (UROA) on colon inflammation and to assess whether UROA is the main anti-inflammatory compound. In addition, the effect of the inflammation on the phenolic metabolism was also explored. Male Fisher rats were fed with 250 mg kg(-1) day(-1) pomegranate extract (PE) or 15 mg kg(-1) day(-1) UROA for 25 days. Dextran sodium sulfate (5%) (DSS) was administered for the five last days and then rats were euthanized. DSS is a well-known model of inflammatory bowel disease. Colon tissue damage, microbiota changes, antioxidant status, prostaglandin E(2) (PGE(2)), nitric oxide production, inducible nitric oxide synthase (iNOS), prostaglandin E synthase (PTGES), gene expression (microarrays and RT-PCR) and polyphenol metabolism (LC-MS-MS) were evaluated. Both PE and UROA decreased inflammation markers (iNOS, cycloxygenase-2, PTGES and PGE(2) in colonic mucosa) and modulated favorably the gut microbiota. The G(1) to S cell cycle pathway was up-regulated in both groups. UROA group showed various down-regulated pathways, including that of the inflammatory response. PE, but not UROA, decreased oxidative stress in plasma and colon mucosa. Only UROA preserved colonic architecture. The normal formation of urolithins in PE-fed rats was prevented during inflammation. Our results suggest that UROA could be the most active anti-inflammatory compound derived from pomegranate ingestion in healthy subjects, whereas in colon inflammation, the effects could be due to the nonmetabolized ellagitannin-related fraction.

  14. MAG-EPA reduces severity of DSS-induced colitis in rats.

    PubMed

    Morin, Caroline; Blier, Pierre U; Fortin, Samuel

    2016-05-15

    Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the intestinal mucosa of the large bowel. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines involved in UC pathogenesis. The aim of this study was to determine the preventive and therapeutic potential of eicosapentaenoic acid monoglyceride (MAG-EPA) in an in vivo rats model of UC induced by dextran sulfate sodium (DSS). DSS rats were untreated or treated per os with MAG-EPA. Morphological, histological, and biochemical analyses were performed following MAG-EPA administrations. Morphological and histological analyses revealed that MAG-EPA pretreatment (12 days pre-DSS) and treatment (6 days post-DSS) exhibited strong activity in reducing severity of disease in DSS rats. Following MAG-EPA administrations, tissue levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 were markedly lower compared with rats treated only with DSS. MAG-EPA per os administration decrease neutrophil infiltration in colon tissues, as depicted by myelohyperoxidase activity. Results also revealed a reduced activation of NF-κB pathways correlated with a decreased expression of COX-2 in colon homogenates derived from MAG-EPA-pretreated and treated rats. Tension measurements performed on colon tissues revealed that contractile responses to methacholine and relaxing effect induced by sodium nitroprusside were largely increased following MAG-EPA treatment. The combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in DSS rats.

  15. Quality of Methods Reporting in Animal Models of Colitis

    PubMed Central

    Bramhall, Michael; Flórez-Vargas, Oscar; Stevens, Robert; Brass, Andy

    2015-01-01

    Background: Current understanding of the onset of inflammatory bowel diseases relies heavily on data derived from animal models of colitis. However, the omission of information concerning the method used makes the interpretation of studies difficult or impossible. We assessed the current quality of methods reporting in 4 animal models of colitis that are used to inform clinical research into inflammatory bowel disease: dextran sulfate sodium, interleukin-10−/−, CD45RBhigh T cell transfer, and 2,4,6-trinitrobenzene sulfonic acid (TNBS). Methods: We performed a systematic review based on PRISMA guidelines, using a PubMed search (2000–2014) to obtain publications that used a microarray to describe gene expression in colitic tissue. Methods reporting quality was scored against a checklist of essential and desirable criteria. Results: Fifty-eight articles were identified and included in this review (29 dextran sulfate sodium, 15 interleukin-10−/−, 5 T cell transfer, and 16 TNBS; some articles use more than 1 colitis model). A mean of 81.7% (SD = ±7.038) of criteria were reported across all models. Only 1 of the 58 articles reported all essential criteria on our checklist. Animal age, gender, housing conditions, and mortality/morbidity were all poorly reported. Conclusions: Failure to include all essential criteria is a cause for concern; this failure can have large impact on the quality and replicability of published colitis experiments. We recommend adoption of our checklist as a requirement for publication to improve the quality, comparability, and standardization of colitis studies and will make interpretation and translation of data to human disease more reliable. PMID:25989337

  16. Diagnostic imaging advances in murine models of colitis

    PubMed Central

    Brückner, Markus; Lenz, Philipp; Mücke, Marcus M; Gohar, Faekah; Willeke, Peter; Domagk, Dirk; Bettenworth, Dominik

    2016-01-01

    Inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary non-invasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography, discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD. PMID:26811642

  17. AOM/DSS Model of Colitis-Associated Cancer.

    PubMed

    Parang, Bobak; Barrett, Caitlyn W; Williams, Christopher S

    2016-01-01

    Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in particular, have enabled fast and efficient analysis of genetic and environmental modulators of CAC without the added requirement of time-intensive genetic crossings. Here we describe the Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) mouse model of inflammatory colorectal cancer. PMID:27246042

  18. Effects of Carum carvi L. (Caraway) extract and essential oil on TNBS-induced colitis in rats.

    PubMed

    Keshavarz, A; Minaiyan, M; Ghannadi, A; Mahzouni, P

    2013-01-01

    Carum carvi L. (Apiaceae family) or caraway is a common household plant grown around the world including Iran. Caraway fruits are used as flavoring agent in foods and beverages, and have various traditional uses in ethnomedicine. Anti-inflammatory, spasmolytic, antimicrobial, antioxidant, carminative and immunomodulatory properties of caraway suggest that it might exert beneficial effects on inflammatory bowel disease (IBD). Therefore, this study was carried out to investigate the effects of caraway hydroalcoholic extract (CHE) and its essential oil (CEO) in an immunological model of colitis in rats induced by trinitrobenzene sulfonic acid (TNBS). Different doses of CHE (100, 200, 400 mg/kg) and CEO (100, 200, 400 μl/kg) were administered orally (p.o.) and also doses of CHE (100, 400 mg/kg) and CEO (100, 400 μl/kg) were given intraperitoneally (i.p.) to the separate groups of male Wistar rats (n=6). Administration of the doses started 6 h after induction of colitis and continued daily for 5 consecutive days. Wet colon weight/length ratio was measured and tissue damage scores as well as indices of colitis were evaluated both macroscopically and histopathologically. CHE and CEO at all doses tested were effective in reducing colon tissue lesions and colitis indices and the efficacy was nearly the same when different doses of plant fractions were administered p.o. or i.p. Administration of prednisolone (p.o., 4 mg/kg), Asacol® (mesalazine microgranules, p.o., 100 mg/kg) and hydrocortisone acetate (i.p., 20 mg/kg) as references were effective in reducing colon tissue injures as well. These data suggest that caraway fractions are both effective and possess anti-colitic activity irrespective of the dose and route of administration.

  19. Nicotine Inhibits Clostridium difficile Toxin A-Induced Colitis but Not Ileitis in Rats

    PubMed Central

    Vigna, Steven R.

    2016-01-01

    Nicotine is protective in ulcerative colitis but not Crohn's disease of the small intestine, but little is known about the effects of nicotine on Clostridium difficile toxin A-induced enteritis. Isolated ileal or colonic segments in anesthetized rats were pretreated with nicotine bitartrate or other pharmacological agents before intraluminal injection of toxin A. After 3 hours, the treated segments were removed and inflammation was assessed. Nicotine biphasically inhibited toxin A colitis but not ileitis. Pretreatment with the nicotinic receptor antagonist, hexamethonium, blocked the effects of nicotine. Pretreating the colonic segments with hexamethonium before toxin A administration resulted in more inflammation than seen with toxin A alone, suggesting that a tonic nicotinic anti-inflammatory condition exists in the colon. Nicotine also inhibited toxin A-induced increased colonic concentrations of the TRPV1 (transient receptor potential vanilloid subtype 1) agonist, leukotriene B4 (LTB4), and release of the proinflammatory neuropeptide, substance P. Pretreatment with nicotine did not protect against direct TRPV1-mediated colitis caused by intraluminal capsaicin. Nicotinic cholinergic receptors tonically protect the colon against inflammation and nicotine inhibits toxin A colitis but not toxin A ileitis in rats in part by inhibition of toxin A-induced activation of TRPV1 by endogenous TRPV1 agonists such as LTB4. PMID:26881175

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

    PubMed

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

    2015-05-01

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

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

    PubMed

    Nagib, Marwa M; Tadros, Mariane G; ElSayed, Moushira I; Khalifa, Amani E

    2013-08-15

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

  2. Dietary protocatechuic acid ameliorates dextran sulphate sodium-induced ulcerative colitis and hepatotoxicity in rats.

    PubMed

    Farombi, Ebenezer O; Adedara, Isaac A; Awoyemi, Omolola V; Njoku, Chinonye R; Micah, Gabriel O; Esogwa, Cynthia U; Owumi, Solomon E; Olopade, James O

    2016-02-01

    The present study investigated the antioxidant and anti-inflammatory effects of dietary protocatechuic acid (PCA), a simple hydrophilic phenolic compound commonly found in many edible vegetables, on dextran sulphate sodium (DSS)-induced ulcerative colitis and its associated hepatotoxicity in rats. PCA was administered orally at 10 mg kg(-1) to dextran sulphate sodium exposed rats for five days. The result revealed that administration of PCA significantly (p < 0.05) prevented the incidence of diarrhea and bleeding, the decrease in the body weight gain, shortening of colon length and the increase in colon mass index in DSS-treated rats. Furthermore, PCA prevented the increase in the plasma levels of pro-inflammatory cytokines, markers of liver toxicity and markedly suppressed the DSS-mediated elevation in colonic nitric oxide concentration and myeloperoxidase activity in the treated rats. Administration of PCA significantly protected against colonic and hepatic oxidative damage by increasing the antioxidant status and concomitantly decreased hydrogen peroxide and lipid peroxidation levels in the DSS-treated rats. Moreover, histological examinations confirmed PCA chemoprotection against colon and liver damage. Immunohistochemical analysis showed that PCA significantly inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in the colon of DSS-treated rats. In conclusion, the effective chemoprotective role of PCA in colitis and the associated hepatotoxicity is related to its intrinsic anti-inflammatory and anti-oxidative properties.

  3. Protective effect of royal jelly in 2,4,6 trinitrobenzene sulfonic acid-induced colitis in rats

    PubMed Central

    Karaca, Turan; Uz, Yesim Hulya; Demirtas, Selim; Karaboga, Ihsan; Can, Guray

    2015-01-01

    Objective(s): In the present study, we evaluated immunological and immunomodulatory properties of royal jelly (RJ) in 2,4,6 trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Materials and Methods: Eighteen adult female Wistar albino rats were divided into three groups of six animals each: a control group that received only saline solution, a TNBS-induced colitis group, and a TNBS-colitis+RJ group that received 250 mg/kg/day of RJ for seven days before the induction of colitis, following by the same treatment for an additional seven days. At the end of the experiment, cardiac blood and colon samples were obtained under deep anaesthesia from the animals in all groups. Serum interleukin-1β (IL-1β), tumour necrosis factor-alpha (TNF-α) and IL-10 levels were analyzed with an enzyme-linked immunosorbent assay (ELISA). Five-micrometre-thick sections were stained with haematoxylin-eosin (H&E) for microscopic evaluations. For immunohistochemical evaluations, the paraffin sections were stained with anti-CD3 (cluster of differentiation), anti-CD5, anti-CD8 and anti-CD45. Results: The results showed that the oral RJ treatment inhibited proinflammatory cytokines, IL-1β and TNF-α secretion, while increasing anti-inflammatory cytokine IL-10 production in the TNBS-induced colitis+RJ group compared with the colitis group not treated with RJ. The colitis was not as severe in the colitis+RJ group, with ulcerative damage, weight loss and inflammatory scores suggesting that impaired CD3-, CD5-, CD8- and CD45-positive T cell immune responses likely mediated the anti-inflammatory effect. Conclusion: The antioxidant and anti-inflammatory properties of RJ protected colon mucosa against TNBS-induced colitis in rats orally treated with RJ. PMID:26019800

  4. Anti-inflammatory effect of ondansetron through 5-HT3 receptors on TNBS-induced colitis in rat

    PubMed Central

    Motavallian-Naeini, Azadeh; Minaiyan, Mohsen; Rabbani, Mohammad; Mahzuni, Parvin

    2012-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestinal tract whose etiology has not yet been fully elucidated. Available medicines for treatment of IBD are not universally effective and result in marked deleterious effects. This challenge has thus heightened the need for research in order to adopt new therapeutic approaches for the treatment of IBD. 5-HT3 receptor antagonists have shown analgesic and anti-inflammatory properties in vitro and in vivo. Our aim was to investigate the effect of ondansetron, 5-HT3 receptor antagonist, in an immune-based animal model of IBD, trinitrobenzene sulfonic acid (TNBS)-induced rat colitis and probable involvement of 5-HT3 receptors. Two hours after induction of colitis (instillation of 50 mg/kg of TNBS dissolved in 0.25 ml of ethanol 50 % v/v) to male Wistar rats, ondansetron (2 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, 5 mg/kg), a 5-HT3 receptor agonist, or ondansetron + mCPBG were administrated intraperitoneally (ip) and continued daily for six days. The animals were sacrificed and distal colons were assessed macroscopically, histologically and biochemically [myeloperoxidase (MPO), tumor necrosis factor-alpha, interleukin-6 and interleukin-1 beta]. Ondansetron and dexamethasone resulted in a decrease in macroscopic and microscopic colonic damage significantly. In addition a dramatic reduction in MPO activity and colonic levels of inflammatory cytokines were seen. The protective effects of ondansetron were antagonized by concurrent administration of mCPBG. Our data suggests that the beneficial effects of ondansetron in TNBS-induced colitis could be mediated by 5-HT3 receptors. PMID:27350767

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

    SciTech Connect

    Nagib, Marwa M.; Tadros, Mariane G.; ELSayed, Moushira I.; Khalifa, Amani E.

    2013-08-15

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

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

    PubMed

    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.

  7. Comparative Protective Effect of Hawthorn Berry Hydroalcoholic Extract, Atorvastatin, and Mesalamine on Experimentally Induced Colitis in Rats

    PubMed Central

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

    2013-01-01

    Abstract The protective effect of hydroalcoholic extract of hawthorn berries (HBE) on acetic acid (AA)–induced colitis in rats was investigated. Forty-two Wistar rats were divided into seven groups, including control and test groups (n=6). The control animals received saline, and the test animals were treated with saline (sham group), mesalamine (50 mg/kg; M group), atorvastatin (20 mg/kg; A group), HBE (100 mg/kg; H group), mesalamine and HBE (HM group), or atorvastatin plus HBE (HA group), 3 days before and a week after colitis induction. Colitis was induced by administration of 1 mL AA (4%) via a polyethylene catheter intrarectally. High-performance liquid chromatography analyses showed that HBE contained 0.13% and 0.5% oleanolic acid and ursolic acid, respectively. Elevated myeloperoxidase activity and lipid peroxidation were attenuated in the HA group. The H and HM groups showed marked reductions in colitis-induced decreases in total thiol molecules and body weight. The histopathological studies revealed that HBE decreased colitis-induced edema and infiltration of neutrophils. Our data suggest the anti-inflammatory and antioxidant effects of HBE and atorvastatin protect against AA-induced colitis. The anti-inflammatory effect of HBE may be attributable to its ability to decrease myeloperoxidase activity as a biomarker of neutrophil infiltration. PMID:23875899

  8. Efficacy of quercetin derivatives in prevention of ulcerative colitis in rats

    PubMed Central

    Nosalova, Viera; Navarova, Jana

    2013-01-01

    Reactive oxygen species has been implicated to contribute significantly to tissue injury associated with ulcerative colitis. Thus compounds with antioxidant properties could be potential therapeutic agents in this disease. Flavonoid compounds are known to possess antioxidative and antiinflammatory properties. Two derivatives of the flavonoid quercetin (Q), chloronaphthoquinone quercetin (CNC) and monochloropivaloyl quercetin (MCP), showed improved antioxidant properties and moreover, they efficiently inhibited aldose reductase activity in vitro. The aim of the work was to test the potential efficacy of quercetin and these synthetic derivatives in vivo in prevention of intestinal inflammation during ulcerative colitis in rats. Colitis was induced by intracolonic administration of acetic acid (4% solution). The control group received the same volume of saline. The vehicle dimethyl sulfoxide (DMSO) and the drugs Q, CNC or MCP were administered orally two hours and then one hour before the acetic acid or saline instillation. After 48 hours, the animals were sacrificed and the colon was weighed, measured and scored for visible damage. Acetic acid triggered an intense inflammatory response of the colon, characterised by haemorrhage, ulceration and bowel wall thickening. From the drugs tested, only CNC (2 × 50 mg/kg) effectively depressed inflammatory damage of the colon. The mechanism of this beneficial effect remains to be elucidated. PMID:24170973

  9. Moxibustion regulates inflammatory mediators and colonic mucosal barrier in ulcerative colitis rats

    PubMed Central

    Ma, Tie-Ming; Xu, Na; Ma, Xian-De; Bai, Zeng-Hua; Tao, Xing; Yan, Hong-Chi

    2016-01-01

    AIM: To observe the efficacy and mechanism of grain-sized moxibustion at different acupoints in a rat model of ulcerative colitis (UC). METHODS: Sprague-Dawley rats were randomly divided into control, UC model, grain-sized moxibustion at a single acupoint (CV 12), grain-sized moxibustion at two acupoints (CV 12 and CV 4), grain-sized moxibustion at three acupoints (CV 12, CV 4, and ST 36), and medication groups (n = 8/group). The UC model was established by enema of trinitrobenzene sulfonic acid. Direct moxibustion was used once a day for 7 d. Disease activity index (DAI) was evaluated before and after the treatment. Morphologic changes of intestinal tissue were observed under an optical microscope. The expression of tumor necrosis factor (TNF)-α and p38 mitogen-activated protein kinase (p38MAPK) in colonic tissue was detected using Western blot, and the levels of occludin and zonula occludens-1 (ZO-1) mRNAs were detected using reverse transcription PCR. RESULTS: Compared with the control group, the intestinal mucosae were incomplete in the model group, glandular structures were irregular, and submucosae were edematous, hyperemic, and infiltrated with inflammatory cells. The DAI scores and expression of TNF-α and p38MAPK were increased significantly in the model group compared to controls (Ps < 0.01), while the mRNA levels of occludin and ZO-1 were reduced significantly (Ps < 0.01). Compared with the model group, colonic mucosa and the arrangement of glands were complete and regular in the treatment groups. DAI scores and the expression of TNF-α and p38MAPK were reduced significantly in moxibustion groups compared to controls (Ps < 0.01), while the mRNA levels of occludin and ZO-1 were increased significantly (Ps < 0.01). The improvements in the above indices in the three acupoints group and the medication group were superior to those in the single and two acupoints groups (all P < 0.05). CONCLUSION: Reduction of TNF-α and p38MAPK and increased expression of

  10. Effect of traditional Chinese medicinal enemas on ulcerative colitis of rats

    PubMed Central

    Guo, Song-Ming; Tong, Hong-Bin; Bai, Lian-Song; Yang, Wei

    2004-01-01

    AIM: To investigate the effects of traditional Chinese medicinal enema (TCME) on inflammatory and immune response of colonic mucosa of rats with ulcerative colitis (UC), and to observe the pathogenic mechanism. METHODS: Thirty UC rats, induced by intestinal enema together with 2.4-dinitrochlorobenzene (DNCB) and acetic acid, were randomly divided into 3 groups, i.e., G I, G II and G III. Groups G I and G II were administered with TCME and salazosulfapyridine enema (SASPE), respectively. Group G III was clystered with only normal saline (NSE), served as control. Group G IV was taken from normal rats as reference, once daily, from the 7th day after the establishment of UC for total 28 d. Interleukin-6 (IL-6) in the colonic mucosa was assayed by 3H-TdR incorporation assay. Colonic mucosal lymphocyte subpopulation adhesive molecules, CD4+CD11a+, CD4+CD18+, CD8+CD11a+, CD8+CD18+ (LSAM), tumor necrosis factor (TNF)-α, and interferon-γ (IFN-γ), were detected by enzyme linked immunosorbent assay (ELISA). Moreover, the expression of TNF-α mRNA and IFN-γ mRNA in colonic mucosa were detected by polymerase chain reaction (RT-PCR). RESULTS: Before therapies, in model groups, G I, G II and G III, levels of IL-6, TNF-α, IFN-γ, CD8+CD11a+ and CD8+CD18+ were significantly different (38.29 ± 2.61 U/mL, 16.54 ± 1.23 ng/L, 8.61 ± 0.89 ng/L, 13.51% ± 2.31% and 12.22% ± 1.13%, respectively) compared to those in G IV group (31.56 ± 2.47 U/mL, 12.81 ± 1.38 ng/L, 5.28 ± 0.56 ng/L, 16.68% ± 1.41% and 16.79% ± 1.11%, respectively). After therapeutic enemas, in G I group, the contents of IL-6 (32.48 ± 2.53 U/m), TNF-α (13.42 ± 1.57 ng/L) and IFN-γ (5.87 ± 0.84 ng/L) were reduced; then, the contents of CD8+CD11a+ (16.01% ± 1.05 %) and CD8+CD18+ (16.28% ± 0.19%) were raised. There was no significant difference between groups G I and G IV, but the difference between groups G I and G II was quite obvious (P < 0.05). The expressions of TNF-α mRNA and IFN-γ mRNA in group G

  11. Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Dextran Sulfate Sodium-Induced Severe Colitis in Rats.

    PubMed

    Onishi, Reizo; Ohnishi, Shunsuke; Higashi, Ryosuke; Watari, Michiko; Yamahara, Kenichi; Okubo, Naoto; Nakagawa, Koji; Katsurada, Takehiko; Suda, Goki; Natsuizaka, Mitsuteru; Takeda, Hiroshi; Sakamoto, Naoya

    2015-01-01

    Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine. Recently, several studies have shown that MSCs can be easily isolated from human amnion. In this study, we investigated the therapeutic effect of human amnion-derived MSCs (AMSCs) in rats with severe colitis. Colitis was induced by the administration of 8% dextran sulfate sodium (DSS) from day 0 to day 5, and AMSCs (1 × 10(6) cells) were transplanted intravenously on day 1. Rats were sacrificed on day 5, and the colon length and histological colitis score were evaluated. The extent of inflammation was evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. The effect of AMSCs on the inflammatory signals was investigated in vitro. AMSC transplantation significantly ameliorated the disease activity index score, weight loss, colon shortening, and the histological colitis score. mRNA expression levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and migration inhibitory factor (MIF) were significantly decreased in the rectums of AMSC-treated rats. In addition, the infiltration of monocytes/macrophages was significantly decreased in AMSC-treated rats. In vitro experiments demonstrated that activation of proinflammatory signals induced by TNF-α or lipopolysaccharide (LPS) in immortalized murine macrophage cells (RAW264.7) was significantly attenuated by coculturing with AMSCs or by culturing with a conditioned medium obtained from AMSCs. Although the phosphorylation of IκB induced by TNF-α or LPS was not inhibited by the conditioned medium, nuclear translocation of NF-κB was significantly inhibited by the conditioned medium. Taken together, AMSC transplantation provided significant improvement in rats with severe colitis, possibly through the inhibition of monocyte/macrophage activity and through inhibition of NF-κB activation. AMSCs could be considered as a new cell source for the

  12. Inulin and fructo-oligosaccharides have divergent effects on colitis and commensal microbiota in HLA-B27 transgenic rats.

    PubMed

    Koleva, Petya T; Valcheva, Rosica S; Sun, Xu; Gänzle, Michael G; Dieleman, Levinus A

    2012-11-14

    Modulation of intestinal microbiota by non-digestible carbohydrates may reduce inflammation in inflammatory bowel disease (IBD). The aim of the present study was to assess the effects of inulin and fructo-oligosaccharides (FOS) on intestinal microbiota and colitis in HLA-B27 transgenic rats, a well-validated rodent model for IBD. In this study, 4-week-old rats were fed 8 g/kg body weight inulin or FOS for 12 weeks, or not. Faeces were collected at 4 and 16 weeks of age; and caecal samples were collected at necropsy. The effects of inulin and FOS on chronic intestinal inflammation were assessed using a gross gut score, histology score and levels of mucosal IL-1β. Intestinal microbiota were characterised by quantitative PCR and denaturing gradient gel electrophoresis. Colitis was significantly reduced in all FOS-fed rats compared to the control diet, whereas inulin decreased chronic intestinal inflammation in only half the number of animals. Quantitative analysis of caecal microbiota demonstrated that inulin increased the numbers of total bacteria and the Bacteroides-Prevotella-Porphyromonas group, FOS increased bifidobacteria, and both fructans decreased Clostridium cluster XI. In the faecal samples, both inulin and FOS decreased total bacteria, Bacteroides-Prevotella-Porphyromonas group, and Clostridium clusters XI and XIVa. FOS increased Bifidobacterium spp., and mediated a decrease of gene copies of Enterobacteriaceae and Clostridium difficile toxin B in faeces. SCFA concentrations in the faecal and caecal samples were unaffected by the diets. In conclusion, FOS increased the abundance of Bifidobacterium spp., whereas both fructans reduced Clostridium cluster XI and C. difficile toxin gene expression, correlating with a reduction of chronic intestinal inflammation.

  13. Development of novel budesonide pellets based on CODESTM technology: In vitro/in vivo evaluation in induced colitis in rats

    PubMed Central

    Varshosaz, J.; Emami, J.; Tavakoli, N.; Minaiyan, M.; Rahmani, N.; Dorkoosh, F.; Mahzouni, P.

    2011-01-01

    Background and the purpose of the study Budesonide is the drug of choice for treatment of active inflammatory bowel disease (IBD). The aim of this study was to develop budesonide pellets based on a novel colon drug delivery system (CODES). Methods Pellet cores containing lactulose or mannitol were prepared by extrusion/spheronization and coated with an acid soluble polymer (Eudragit E100), hydroxypropylmethyl cellulose (HPMC) and an enteric coat (Eudragit FS 30D) sequentially. In vitro drug release of coated pellets was studied using USP dissolution apparatus type II in buffers of pH 1.2 (2 hrs), pH of 7.4 (4 hrs) and pH of 6.8 containing 8% rat cecal contents (RCC) (18 hrs). The efficacy of the optimized formulation (containing 50% lactulose coated with Eudragit E (30% w/w) and Eudragit FS 30D (12% w/w)) was evaluated against 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Results The results of the kind of bacteria in vitro dissolution tests indicated absence of drug release in pHs of 1.2 and 7.4 and controlled release in buffer of pH 6.8 containing RCC. It was found that release rate was controlled by the type and amount of polysaccharide and the thickness of the acid soluble layer. The prepared formulation showed promising results in alleviating the conditions of experimental model of colitis. Conclusion The results of this study suggest that pellets based on CODES technology could be useful for colonic delivery of budesonide. PMID:22615647

  14. Effects of four regulating-intestine prescriptions on pathology and ultrastructure of colon tissue in rats with ulcerative colitis

    PubMed Central

    Fan, Heng; Qiu, Ming-Yi; Mei, Jia-Jun; Shen, Guan-Xin; Liu, Song-Lin; Chen, Rui

    2005-01-01

    AIM: To observe different histomorphologic changes of ulcerative colitis (UC) rats that were treated with four regulating-intestine prescriptions (FRIP), to investigate the curative effects of FRIP and to analyze their treatment mechanism. METHODS: The UC rat model was made by the method of 2,4-dinitro chloro benzene (DNCB) immunity and acetic acid local enema. Ninety-eight SD rats were randomly divided into seven groups, namely, the normal control group, model group, salicylazosulfapyridine (SASP) group, Wumeiwan (WMW) group, Baitouwengtang (BTWT) group, Senglingbaishusan (SLBSS) group, and Tongxieyaofang (TXYF) group. Each group had 14 rats (with equal ratio of male and female). The six animal model groups of UC -SASP, TXYF, WMW, BTWT, SLBSS, TXYF-were treated by distilled water except the normal control group. Changes of the rat’s general conditions after treatment were respectively observed, the colon tissue damage scores were given out, the pathology of colonic mucosa and changes of ultrastructure were analyzed. RESULTS: Different pathological changes on histology were shown after treatment by FRIP. The colon tissue damage score in model group was higher than that of FRIP groups and SASP group (q = 4.59, 4.77, P<0.05 or q = 5.48, 6.25, 5.97, P<0.01). The scores of WMW group, BTWT group and SLBSS group were lower than that of SASP (q = 4.13, P<0.05 or q = 5.31, 5.12, P<0.01). There was no remarkable difference between the damage score of TXYF group and SASP group (q = 3.75, P>0.05). In addition, some apoptosis cells were found in the pathologic control group. CONCLUSION: The model made with DNCB and acetic acid was successful, and FRIP had better curative effect and WMW was the best curative effect, BTW, SLBSS and TXYF were similar to SASP, and we discovered that apoptosis was possibly related to UC. PMID:16097047

  15. Pectin Film Coated Pellets for Colon-targeted Delivery of Budesonide: In-vitro/In-vivo Evaluation in Induced Ulcerative Colitis in Rat

    PubMed Central

    Varshosaz, Jaleh; Emami, Jaber; Tavakoli, Naser; Minaiyan, Mohsen; Rahmani, Nakisa; Dorkoosh, Farid; Mahzouni, Parvin

    2012-01-01

    The main objective of this study was to prepare colon-specific pellets of budesonide, using pectin as film coating. Pellet cores of budesonide were prepared by extrusion / spheronization technique. Pectin, in different ratios was combined with Eudragit RS30D, Eudragit NE30D or Surelease to produce film coating. The dissolution profiles of pectin coated pellets were investigated in pH of 1.2 (2 h), pH of 7.4 (4 h) and pH of 6.8 in the absence as well as presence of rat cecal contents (18 h). Finally the selected formulation was evaluated on trinitrobenzenesulfonic acid (TNBS) induced ulcerative colitis in rat model, in comparison with conventional UC treatments. The dissolution profiles of pectin coated pellets showed that the release of budesonide in presence of rat cecal content depended on adjuvant polymer, the ratio of pectin to polymer and film thickness. Coated pellets, prepared out of pectin and Surelease at a ratio of 1:3 at coating level of 35% (w/w), could increase budesonide release statistically in presence of rat cecal content, while they released no drug in pH of 1.2 and 7.4. Animal experiments revealed the therapeutic efficacy of pectin/Surelease-coated pellets of budesonide in alleviating the conditions of TNBS-induced colitis model as reflected by weight gain, as well as improvement of clinical, macroscopic and microscopic parameters of induced colitis. This confirmed the ability of the optimized formulation for targeted drug delivery of budesonide to colon. PMID:24250500

  16. Anti-inflammatory effect of Prunus armeniaca L. (Apricot) extracts ameliorates TNBS-induced ulcerative colitis in rats.

    PubMed

    Minaiyan, M; Ghannadi, A; Asadi, M; Etemad, M; Mahzouni, P

    2014-01-01

    Prunus armeniaca L. (Apricot) is a tree cultivated in different parts of the world. Apricot kernel as a good dietary supplement has shown antioxidant, anti-inflammatory and other pharmacologic properties which suggest that it may be functional as an anticolitis agent. In this study we evaluated the effects of apricot kernel extract and oil on ulcerative colitis in rats. Rats were fasted for 36 h before the experiment. Colitis was induced by intra-rectal instillation of 50 mg/kg trinitrobenzene sulfonic acid in male Wistar rats. Treatments were started 6 h after colitis induction and continued every 24 h for 5 days. Apricot kernel extract (100, 200, 400 mg/kg p.o. and 100, 400 mg/kg i.p.) and apricot kernel extract/oil (100, 200, 400 mg/kg p.o.) were used as experimental treatments and prednisolone (4 mg/kg p.o. or i.p.) was used as reference drug. On the day 6, colon tissue was removed and macroscopic and pathologic parameters were evaluated. Ulcer index and total colitis index as representative of macroscopic and histologic parameters respectively showed ameliorating effects in experimental groups especially those treated by intraperitoneal administration route. Results also demonstrated that oil fraction was not able to potentiate the effects of extract. These data suggest that apricot kernel extracts (with or without oil) can be introduced for further mechanistic and clinical studies as a complementary medicine for inflammatory bowel disorders.

  17. Anti-inflammatory effect of Prunus armeniaca L. (Apricot) extracts ameliorates TNBS-induced ulcerative colitis in rats

    PubMed Central

    Minaiyan, M.; Ghannadi, A.; Asadi, M.; Etemad, M.; Mahzouni, P.

    2014-01-01

    Prunus armeniaca L. (Apricot) is a tree cultivated in different parts of the world. Apricot kernel as a good dietary supplement has shown antioxidant, anti-inflammatory and other pharmacologic properties which suggest that it may be functional as an anticolitis agent. In this study we evaluated the effects of apricot kernel extract and oil on ulcerative colitis in rats. Rats were fasted for 36 h before the experiment. Colitis was induced by intra-rectal instillation of 50 mg/kg trinitrobenzene sulfonic acid in male Wistar rats. Treatments were started 6 h after colitis induction and continued every 24 h for 5 days. Apricot kernel extract (100, 200, 400 mg/kg p.o. and 100, 400 mg/kg i.p.) and apricot kernel extract/oil (100, 200, 400 mg/kg p.o.) were used as experimental treatments and prednisolone (4 mg/kg p.o. or i.p.) was used as reference drug. On the day 6, colon tissue was removed and macroscopic and pathologic parameters were evaluated. Ulcer index and total colitis index as representative of macroscopic and histologic parameters respectively showed ameliorating effects in experimental groups especially those treated by intraperitoneal administration route. Results also demonstrated that oil fraction was not able to potentiate the effects of extract. These data suggest that apricot kernel extracts (with or without oil) can be introduced for further mechanistic and clinical studies as a complementary medicine for inflammatory bowel disorders. PMID:25657793

  18. Anti-inflammatory effect of Prunus armeniaca L. (Apricot) extracts ameliorates TNBS-induced ulcerative colitis in rats.

    PubMed

    Minaiyan, M; Ghannadi, A; Asadi, M; Etemad, M; Mahzouni, P

    2014-01-01

    Prunus armeniaca L. (Apricot) is a tree cultivated in different parts of the world. Apricot kernel as a good dietary supplement has shown antioxidant, anti-inflammatory and other pharmacologic properties which suggest that it may be functional as an anticolitis agent. In this study we evaluated the effects of apricot kernel extract and oil on ulcerative colitis in rats. Rats were fasted for 36 h before the experiment. Colitis was induced by intra-rectal instillation of 50 mg/kg trinitrobenzene sulfonic acid in male Wistar rats. Treatments were started 6 h after colitis induction and continued every 24 h for 5 days. Apricot kernel extract (100, 200, 400 mg/kg p.o. and 100, 400 mg/kg i.p.) and apricot kernel extract/oil (100, 200, 400 mg/kg p.o.) were used as experimental treatments and prednisolone (4 mg/kg p.o. or i.p.) was used as reference drug. On the day 6, colon tissue was removed and macroscopic and pathologic parameters were evaluated. Ulcer index and total colitis index as representative of macroscopic and histologic parameters respectively showed ameliorating effects in experimental groups especially those treated by intraperitoneal administration route. Results also demonstrated that oil fraction was not able to potentiate the effects of extract. These data suggest that apricot kernel extracts (with or without oil) can be introduced for further mechanistic and clinical studies as a complementary medicine for inflammatory bowel disorders. PMID:25657793

  19. The influence of pretreatment with ghrelin on the development of acetic-acid-induced colitis in rats.

    PubMed

    Maduzia, D; Matuszyk, A; Ceranowicz, D; Warzecha, Z; Ceranowicz, P; Fyderek, K; Galazka, K; Dembinski, A

    2015-12-01

    Ghrelin has been primarily shown to exhibit protective and therapeutic effect in the gut. Pretreatment with ghrelin inhibits the development of acute pancreatitis and accelerates pancreatic recovery in the course of this disease. In the stomach, ghrelin reduces gastric mucosal damage induced by ethanol, stress or alendronate, as well as accelerates the healing of acetic acid-induced gastric and duodenal ulcer. The aim of present studies was to investigate the effect of pretreatment with ghrelin on the development of acetic acid-induced colitis. Studies have been performed on male Wistar rats. Animals were treated intraperitoneally with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose). Saline or ghrelin was given twice: 8 and 1 h before induction of colitis. Colitis was induced by a rectal enema with 1 ml of 4% solution of acetic acid and the severity of colitis was assessed 1 or 24 hours after induction of inflammation. Rectal administration of acetic acid induced colitis in all animals. Damage of colonic wall was seen at the macroscopic and microscopic level. This effect was accompanied by a reduction in colonic blood flow and mucosal DNA synthesis. Moreover, induction of colitis significantly increased mucosal concentration of pro-inflammatory interleukin-1β (IL-1β), activity of myeloperoxidase and concentration of malondialdehyde (MDA). Mucosal activity of superoxide dismutase (SOD) was reduced. Pretreatment with ghrelin reduced the area and grade of mucosal damage. This effect was accompanied by an improvement of blood flow, DNA synthesis and SOD activity in colonic mucosa. Moreover, ghrelin administration reduced mucosal concentration of IL-1β and MDA, as well as decreased mucosal activity of myeloperoxidase. Administration of ghrelin protects the large bowel against the development of the acetic acid-induced colitis and this effect seems to be related to the ghrelin-evoked anti-inflammatory and anti-oxidative effects.

  20. The influence of pretreatment with ghrelin on the development of acetic-acid-induced colitis in rats.

    PubMed

    Maduzia, D; Matuszyk, A; Ceranowicz, D; Warzecha, Z; Ceranowicz, P; Fyderek, K; Galazka, K; Dembinski, A

    2015-12-01

    Ghrelin has been primarily shown to exhibit protective and therapeutic effect in the gut. Pretreatment with ghrelin inhibits the development of acute pancreatitis and accelerates pancreatic recovery in the course of this disease. In the stomach, ghrelin reduces gastric mucosal damage induced by ethanol, stress or alendronate, as well as accelerates the healing of acetic acid-induced gastric and duodenal ulcer. The aim of present studies was to investigate the effect of pretreatment with ghrelin on the development of acetic acid-induced colitis. Studies have been performed on male Wistar rats. Animals were treated intraperitoneally with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose). Saline or ghrelin was given twice: 8 and 1 h before induction of colitis. Colitis was induced by a rectal enema with 1 ml of 4% solution of acetic acid and the severity of colitis was assessed 1 or 24 hours after induction of inflammation. Rectal administration of acetic acid induced colitis in all animals. Damage of colonic wall was seen at the macroscopic and microscopic level. This effect was accompanied by a reduction in colonic blood flow and mucosal DNA synthesis. Moreover, induction of colitis significantly increased mucosal concentration of pro-inflammatory interleukin-1β (IL-1β), activity of myeloperoxidase and concentration of malondialdehyde (MDA). Mucosal activity of superoxide dismutase (SOD) was reduced. Pretreatment with ghrelin reduced the area and grade of mucosal damage. This effect was accompanied by an improvement of blood flow, DNA synthesis and SOD activity in colonic mucosa. Moreover, ghrelin administration reduced mucosal concentration of IL-1β and MDA, as well as decreased mucosal activity of myeloperoxidase. Administration of ghrelin protects the large bowel against the development of the acetic acid-induced colitis and this effect seems to be related to the ghrelin-evoked anti-inflammatory and anti-oxidative effects. PMID:26769837

  1. Protective Effect of the Methanolic Extract of Malva parviflora L. leaves on Acetic Acid-induced Ulcerative Colitis in Rats

    PubMed Central

    Dugani, Aisha; Dakhil, Bushra; Treesh, Soad

    2016-01-01

    Background/Aims: Inflammatory bowel disease (IBD) is a general term describing chronic, idiopathic relapsing, inflammatory conditions of the gastrointestinal tract of unknown etiology. Previous studies have indicated that Malva parviflora leaf extract possesses anti-inflammatory, antioxidant, and antiulcerogenic activity. activity. This work aimed to investigatee the anti-inflammatory effect of the methanolic (MEMP) and aqueous (AEMP) extracts of M. parviflora leaves on acetic acid-induced colitis in rats. Materials and Methods: 42 male Wistar albino rats were divided into seven groups (n = 6). Group I: Normal saline control group with no colitis; Group II: Acetic acid colitis group; Group III: 100 mg/kg/5 d MEMP; Group IV: 200 mg/kg/5 d.MEMP; Group V: 100 mg/kg/5 d AEMP; Group VI: 200 mg/kg/5 d AEMP; Group VII: Prednisolone group (2 mg/kg/5 d). Treatments were followed by induction of colitis using intrarectal instillation of 2 mL of 4% acetic acid. Colon damage was evaluated macroscopically (spleen weight/body weight, colon weight/length ratio) and the histological changes were also recorded. Results: The results of this study showed that acetic acid caused severe inflammation of the colon and a significant increase in spleen weight/body weight, and an increase in colon weight/length ratio compared with normal control group. Pretreatment with MEMP and AEMP for 5 days followed by induction of colitis resulted in a significant attenuation of spleen weight and colon weight/length ratio compared with acetic acid control group. Methanolic extract provided better anticolitic effect than aqueous extract; the effect was prominent at the dose of 200 mg/kg. Histopathological findings confirmed the protective effect of the MEMP. Conclusion: In conclusion, MEMP could ameliorate mucosal damage in experimentally induced colitis when given orally. PMID:27184642

  2. Effects of tumour necrosis factor-alpha synthesis inhibitors on rat trinitrobenzene sulphonic acid-induced chronic colitis.

    PubMed

    Bobin-Dubigeon, C; Collin, X; Grimaud, N; Robert, J M; Le Baut, G; Petit, J Y

    2001-11-01

    The fact that tumour necrosis factor-alpha (TNF-alpha) is clearly involved in the pathogenesis of intestinal bowel disease, especially Crohn's disease, suggests that TNF-alpha synthesis inhibitors could be beneficial for treatment. The present study assessed the effect of chronic oral gavage of two in vitro TNF-alpha synthesis inhibitors, JM 34 maleate or [N-(4,6-dimethylpyridin-2-yl)-furane-2-carboxamide)] maleate and XC 21 or (N-betapicolyl-tetrafluorophtalimide), on colonic inflammation in trinitrobenzene sulphonic acid-induced colitis in rats. Rats received JM 34 maleate (100 mg/kg) and XC 21 (50 mg/kg) 1 h before colitis induction and then daily for 8 days by oral gavage. The colon was removed on day 8 and processed for clinical score, myeloperoxidase activity, and soluble TNF-alpha release. Treatment with XC 21, as well as dexamethasone and sulphasalazine, reduced colonic damage and decreased (except with dexamethasone) the incidence of diarrhoea. JM 34 maleate failed to improve the clinical signs of chronic colitis. After trinitrobenzene sulphonic acid-induced colitis, myeloperoxidase activity and TNF-alpha colonic mucosal production were substantially increased compared to the control (saline instillation). Both of these inflammatory indicators were then significantly decreased (P< or =0.05) after the four chronic treatments (JM 34 maleate, XC 21, sulphasalazine, and dexamethasone). XC 21 appeared to be as efficient as sulphasalazine in improving colonic inflammation. PMID:11716848

  3. Effect of ethanolic extract of leaves of Paederia foetida Linn. on acetic acid induced colitis in albino rats

    PubMed Central

    Das, Swarnamoni; Kanodia, Lalit; Mukherjee, Apurba; Hakim, Abdul

    2013-01-01

    Objectives: To evaluate the effect of ethanolic extract of leaves of Paederia foetida on acetic acid induced colitis in albino rats. Materials and Methods: Ethanolic extract of Paederia foetida (EEPF) was prepared by percolation method. Acute toxicity test was done by using Organization for Economic Cooperation and Development guidelines. Albino rats were divided into four groups of five animals each. Groups A and B received 3% gum acacia. Groups C and D received EEPF 500 mg/kg body weight (BW) and 5-aminosalisylic acid 100 mg/kg BW respectively. Colitis was induced by transrectal administration of 4% acetic acid on 5th day. All animals were sacrificed after 48 h of colitis induction and distal 10 cm of the colon was dissected. Colon was weighed for disease activity index (DAI) and scored macroscopically and microscopically. Biochemical assessment of tissue myeloperoxidase (MPO), catalase (CAT) and superoxide dismutase (SOD) was done in colonic tissue homogenate and malondialdehyde (MDA) was estimated in serum. Results: P. foetida showed significant (P < 0.05) reduction in DAI, macroscopic and microscopic lesion score as well as significant (P < 0.05) improvement in MPO, MDA, CAT, and SOD level as compared to Group B. Conclusions: The ethanolic extract of leaves of P. foetida showed significant amelioration of experimentally induced colitis, which may be attributed to its anti-inflammatory and antioxidant property. PMID:24130378

  4. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

    PubMed Central

    Minaiyan, Mohsen; Asghari, Gholamreza; Taheri, Diana; Saeidi, Mozhgan; Nasr-Esfahani, Salar

    2014-01-01

    Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE) and its chloroform fraction (MCF) on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg) were administered orally to separate groups of male Wistar rats, 2 h before ulcer induction (using acetic acid 4%) and continued for 5 days. Prednisolone (4 mg/kg) and normal saline (1 ml/kg) were used in reference and control groups, respectively. All rats were sacrificed 24 h after the last dose (at day 6) and tissue injuries were assessed macroscopically and pathologically. Results: Extracts with three doses mentioned before were effective to reduce weight of distal colon (8 cm) as a marker for inflammation and tissue edema. Three doses of MSHE and two greater doses of MCF (100 and 200 mg/kg) were effective to reduce ulcer severity, area, and index as well as mucosal inflammation severity and extent, crypt damage, invasion involvement, total colitis index, and MPO activity compared with controls. MCF (50 mg/kg) was not significantly effective in reducing evaluated parameters of colitis compared with controls. Conclusion: It is concluded that MSHE and MCF were both effective to treat experimental colitis and this might be attributed to their similar major components, biophenols and flavonoids. Since the efficacy was evident even in low doses of MSHE, presence of active constituents with high potency in seeds is persuasive. PMID:25050310

  5. Hypothalamic paraventricular nucleus stimulation reduces intestinal injury in rats with ulcerative colitis

    PubMed Central

    Deng, Quan-Jun; Deng, Ding-Jing; Che, Jin; Zhao, Hai-Rong; Yu, Jun-Jie; Lu, Yong-Yu

    2016-01-01

    AIM: To investigate the effect and mechanism of stimulation of the hypothalamic paraventricular nucleus with glutamate acid in rats with ulcerative colitis (UC). METHODS: The rats were anesthetized with 10% chloral hydrate via abdominal injection and treated with an equal volume of TNBS + 50% ethanol enema, injected into the upper section of the anus with the tail facing up. Colonic damage scores were calculated after injecting a certain dose of glutamic acid into the paraventricular nucleus (PVN), and the effect of the nucleus tractus solitarius (NTS) and vagus nerve in alleviating UC injury through chemical stimulation of the PVN was observed in rats. Expression changes of C-myc, Apaf-1, caspase-3, interleukin (IL)-6, and IL-17 during the protection against UC injury through chemical stimulation of the PVN in rats were detected by Western blot. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in colon tissues of rats were measured by colorimetric methods. RESULTS: Chemical stimulation of the PVN significantly reduced UC in rats in a dose-dependent manner. The protective effects of the chemical stimulation of the PVN on rats with UC were eliminated after chemical damage to the PVN. After glutamate receptor antagonist kynurenic acid was injected into the PVN, the protective effects of the chemical stimulation of the PVN were eliminated in rats with UC. After AVP-Vl receptor antagonist ([Deamino-penl, val4, D-Arg8]-vasopressin) was injected into NTS or bilateral chemical damage to NTS, the protective effect of the chemical stimulation of PVN on UC was also eliminated. After chemical stimulation of the PVN, SOD activity increased, MDA content decreased, C-myc protein expression significantly increased, caspase-3 and Apaf-1 protein expression significantly decreased, and IL-6 and IL-17 expression decreased in colon tissues in rats with UC. CONCLUSION: Chemical stimulation of the hypothalamic PVN provides a protective effect against UC injury in

  6. Intraperitoneal administration of butyrate prevents the severity of acetic acid colitis in rats

    PubMed Central

    Malago, Joshua J.; Sangu, Catherine L.

    2015-01-01

    Intrarectal infusion of butyrate improves colorectal disorders including ulcerative colitis (UC). However, it is not established whether systemically administered butyrate benefits such patients. The current study aimed at exploring and comparing the potential of intraperitoneally, intrarectally, and orally administered butyrate against acetic acid (AA)-induced UC in rats. Intrarectal administration of 2 ml of 50% AA was done after or without prior treatment of rats for 7 consecutive days with 100 mg/kg sodium butyrate (SB) intraperitoneally, intrarectally, or orally. Rats were sacrificed after 48 h of AA-treatment. Subsequently, colon sections were processed routinely for histopathological examination. We clinically observed diarrhea, loose stools, and hemoccult-positive stools, and histologically, epithelial loss and ulceration, crypt damage, goblet cell depletion, hemorrhage, and mucosal infiltration of inflammatory cells. The changes were significantly reduced by intraperitoneal, intrarectal, or oral butyrate, with intraperitoneal butyrate exhibiting the highest potency. It is concluded that intraperitoneal administration of butyrate abrogates the lesions of AA-induced UC and its potency surpasses that of intrarectal or oral butyrate. PMID:25743124

  7. Effect of Coriandrum sativum hydroalcoholic extract and its essential oil on acetic acid- induced acute colitis in rats

    PubMed Central

    Heidari, Bahareh; Sajjadi, Seyed Ebrahim; Minaiyan, Mohsen

    2016-01-01

    Objective: The aim of this study was to determine the protective effects of Coriandrum sativum on acetic acid-inducedcolitis in rats. C. sativum (Coriander) has long been used in Iranian traditional medicine and its use as an anti-inflammatory agent is still common in some herbal formulations. Materials and Methods: Colitis was induced by intra-rectal administration of 2ml acetic acid 4% in fasted male Wistar rats. Treatment was carried out using three increasing doses of extract (250, 500, 1000 mg/kg) and essential oil (0.25, 0.5, 1 ml/kg) of coriander started 2 h before colitis induction and continued for a five-day period. Colon biopsies were taken for weighting, macroscopic scoring of injured tissue, histopathological examination and measuring myeloperoxidase (MPO) activity. Results: Colon weight was decreased in the groups treated with extract (500 and 1000 mg/kg) and essential oil (0.5 ml/kg) compared to the control group. Regarding MPO levels, ulcer severity and area as well as the total colitis index, same results indicating meaningful alleviation of colitis was achieved after treatment with oral extract and essential oil. Conclusion: Since the present experiment was made by oral fractions of coriander thus the resulting effects could be due to both the absorption of the active ingredients and/or the effect of non-absorbable materials on colitis after reaching the colon. In this regard, we propose more toxicological and clinical experiments to warranty its beneficial application in human inflammatory bowel diseases. PMID:27222834

  8. Anti-inflammatory effect of diosmectite in hapten-induced colitis in the rat.

    PubMed

    González, Raquel; de Medina, Fermin Sánchez; Martínez-Augustin, Olga; Nieto, Ana; Gálvez, Julio; Risco, Severiano; Zarzuelo, Antonio

    2004-03-01

    1. Diosmectite is a natural silicate effectively used in the treatment of infectious diarrhoea. Its antidiarrhoeal properties involve adsorption of toxins and bacteria and modifications of the rheological characteristics of gastrointestinal mucus. Hence, the aim of this study was to test the intestinal anti-inflammatory activity of diosmectite. 2. Diosmectite (500 mg x kg(-1) day(-1), p.o.) was administered as a post-treatment to rats with chronic trinitrobenzene sulphonic acid colitis. Colonic status was checked 1 and 2 weeks after colitis induction by macroscopic, histological and biochemical examination. 3. Diosmectite post-treatment resulted in amelioration of the morphological signs (intestinal weight, macroscopic damage, necrosed area, histology) and biochemical markers (myeloperoxidase activity, glutathione levels, MUC2 expression, inducible nitric oxide synthase and interleukin-1beta (IL-1beta) and leukotriene B(4) synthesis), as well as in the reduction of the severity of diarrhoea. The effect of the clay was comparable to that of sulphasalazine (50 mg x kg(-1) day(-1)). 4. 5. Diosmectite exhibited a dose-dependent capacity to adsorb proteins in vitro as well as a dose-dependent inhibitory effect on the basolateral secretion of IL-8 by lipopolysaccharide (LPS)-stimulated HT29 cells. Diosmectite had a dose-dependent inhibitory effect on IL-1beta production by LPS-stimulated THP-1 cells. 6. The effect of diosmectite on MUC2 was post-transcriptional, since mRNA levels were unaffected. However, diosmectite is able to upregulate MUC2 mRNA levels in HT29-MTX cells. 7. Diosmectite has anti-inflammatory activity administered as a post-treatment. Possible mechanisms include adsorption of luminal antigens, increase of colonic mucin levels and possibly a direct modulatory action of cytokine production by mucosal cells.

  9. Healing Acceleration of Acetic Acid-induced Colitis by Marigold (Calendula officinalis) in Male Rats

    PubMed Central

    Tanideh, Nader; Jamshidzadeh, Akram; Sepehrimanesh, Masood; Hosseinzadeh, Masood; Koohi-Hosseinabadi, Omid; Najibi, Asma; Raam, Mozhdeh; Daneshi, Sajad; Asadi-Yousefabad, Seyedeh-Leili

    2016-01-01

    Background/Aim: Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate healing effects of Calendula officinalis hydroalcoholic extract in experimentally induced UC in rat. Materials and Methods: Ninety-six rats, weighing 200 ± 20 g, were randomly divided into eight equal groups. UC induced by 3% acetic acid and oral doses of C. officinalis extract, 1500 and 3000 mg/kg, and enema (gel 10% and 20%) were given. Two groups as positive controls were given asacol (enema) and oral mesalamine. Negative control groups were given normal saline and base gel. On days 3 and 7, intestinal histopathology and weight changes, plus oxidative stress indices including malondialdehyde (MDA) level and myeloperoxidase (MPO) activity were assayed. Results: A significant increase in the body weight of rats was seen in the group given C. officinalis extract 3000 mg/kg orally, oral mesalamine, and 20% intracolonic gel form of marigold extract compared with negative control and base gel groups during the experimental period. Acute inflammation and granular atrophy after UC induction were resolved completely completely by both 20% intracolonic gel and 3000 mg/kg orally. An increase in MPO activity and a decrease in MDA level in response to oral and intracolonic gel form of C. officinalis were observed 3 and and 7 days after treatment (P < 0.05). Conclusion: Our results indicate that oral and enema forms of hydroalcoholic extract of C. officinalis can be offered as are potential therapeutic agents for UC induced in rats. PMID:26831607

  10. Is Coenzyme Q10 Effective in Protection against Ulcerative Colitis? An Experimental Study in Rats.

    PubMed

    Ewees, Mohamed Gamal; Messiha, Basim Anwar Shehata; Abo-Saif, Ali Ahmed; Abd El-Latif, Hekma Abd El-Tawab

    2016-01-01

    Coenzyme Q10 (Co-Q10) is a vitamin-like supplement which appears to be safe, with minimal side effects and low drug interaction potential. Co-Q10 is used in the treatment of a variety of disorders related primarily to suboptimal cellular energy metabolism and oxidative injury. Studies supporting the efficacy of Co-Q10 appear most promising for a variety of diseases, including ulcerative colitis (UC). The present investigation aims to elucidate the possible protective effects of Co-Q10 against UC, as induced by the administration of iodoacetamide to adult male albino rats. In our study, Co-Q10 showed potent anti-oxidant and anti-inflammatory activities through a significant increase in catalase activity and glutathione content. In addition, it significantly decreased myeloperoxidase activity, malondialdehyde content and nitrate/nitrite production. These results suggest that Co-Q10 protects against UC in rats via anti-oxidant and anti-inflammatory potentials, and therefore seems promising for use in further clinical trials.

  11. Experimental colitis.

    PubMed

    MacPherson, B; Pfeiffer, C J

    1976-01-01

    Ulcerative colitis and Crohn's disease are complex, problematic diseases of unknown etiology in man, and appropriate experimental models would be useful in elucidating their pathogenesis and treatment. Although there have been numerous attempts to produce inflammatory ulcerative colonic disease in laboratory animals resembling those human disease forms, none has been entirely successful. Investigators have conducted experiments involving almost every etiological factor suggested for initiation of these diseases. The methods reviewed in this paper include production of experimental colitis by vascular impairment, and immunological methods such as bacterial infection, allergic reactions, direct and indirect hypersensitivity reactions, as well as autoimmune mechanisms. The results of carrageenan-induced colitis, irradiation, dietary, and drug-induced techniques are also discussed and the frequency and nature of spontaneous colonic lesions in animals is summarized.

  12. Effect of acute and chronic DSS induced colitis on plasma eicosanoid and oxylipin levels in the rat.

    PubMed

    Willenberg, Ina; Ostermann, Annika I; Giovannini, Samoa; Kershaw, Olivia; von Keutz, Anne; Steinberg, Pablo; Schebb, Nils Helge

    2015-07-01

    Eicosanoids and oxylipins are potent lipid mediators involved in the regulation of inflammation. In order to evaluate their role and suitability as biomarkers in colitis, we analyzed their systemic levels in the acute and chronic phase of dextran sulfate sodium (DSS) induced colitis. Male Fischer 344 rats were treated in three cycles with 4% DSS in the drinking water (4 days followed by 10 days recovery) and blood was drawn 3 days prior to the first DSS treatment and on days 4, 11, 32 and 39. Histopathological evaluation of the colon tissue after 42 days showed that the animals developed a mild to severe chronic colitis. Consistently, prostaglandin levels were massively (twofold) elevated in the colonic tissue. LC-MS based targeted metabolomics was used to determine plasma oxylipin levels at the different time points. In the acute phase of inflammation directly after DSS treatment, epoxy-fatty acid (FA), dihydroxy-FA and hydroxy-FA plasma concentrations were uniformly elevated. With each treatment cycle the increase in these oxylipin levels was more pronounced. Our data suggest that in the acute phase of colitis release of polyunsaturated FAs from membranes in the inflamed tissue is reflected by a uniform increase of oylipins formed in different branches of the arachidonic acid cascade. However, during the recovery phases the systemic oxylipin pattern is not or only moderately altered and does not allow to evaluate the onset of chronic inflammation in the colon.

  13. Vitamin A Inhibits Development of Dextran Sulfate Sodium-Induced Colitis and Colon Cancer in a Mouse Model

    PubMed Central

    Okayasu, Isao; Hana, Kiyomi; Nemoto, Noriko; Yoshida, Tsutomu; Saegusa, Makoto; Yokota-Nakatsuma, Aya; Song, Si-Young; Iwata, Makoto

    2016-01-01

    Vitamin A is essential to mucosal immunity and cell differentiation. The fact that lack of it might involve chronic inflammation and increased risk of cancer has been reported. Little is known about the mechanism of vitamin A deficiency in the development of colitis and its influence on development of colorectal cancer. To determine the influence of vitamin A deficiency on colitis and colorectal cancer development, an experimental study using a colitis mouse model was performed. Dextran sulfate sodium (DSS) colitis was induced in vitamin A-deficient and vitamin A-supplemented mice. Further, colorectal carcinoma was induced by a combination of azoxymethane preinjection and DSS colitis. Results were compared between the two groups mainly by immunohistochemical analysis. Colitis was more severe and recovery from colitis was slower in vitamin A-deficient mice than in vitamin A-supplemented mice. Compared with vitamin A-supplemented mice, vitamin A-deficient mice had decreases in colonic subepithelial myofibroblasts and the ratio of mucosal IgA+/IgG+ cells, increases in CD11c+ dendritic cells, and a higher rate of development of colorectal carcinoma with colitis following azoxymethane. Vitamin A lipid droplets in subepithelial myofibroblasts were decreased in vitamin A-deficient mice, suggesting alterations in colonic crypt niche function. Thus, vitamin A inhibited colitis and the development of colorectal cancer. PMID:27298823

  14. Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of Ulcerative Colitis and Colorectal Cancer.

    PubMed

    Marshall, Derek C; Lyman, Susan K; McCauley, Scott; Kovalenko, Maria; Spangler, Rhyannon; Liu, Chian; Lee, Michael; O'Sullivan, Christopher; Barry-Hamilton, Vivian; Ghermazien, Haben; Mikels-Vigdal, Amanda; Garcia, Carlos A; Jorgensen, Brett; Velayo, Arleene C; Wang, Ruth; Adamkewicz, Joanne I; Smith, Victoria

    2015-01-01

    Expression of matrix metalloproteinase 9 (MMP9) is elevated in a variety of inflammatory and oncology indications, including ulcerative colitis and colorectal cancer. MMP9 is a downstream effector and an upstream mediator of pathways involved in growth and inflammation, and has long been viewed as a promising therapeutic target. However, previous efforts to target matrix metalloproteinases (MMPs), including MMP9, have utilized broad-spectrum or semi-selective inhibitors. While some of these drugs showed signs of efficacy in patients, all MMP-targeted inhibitors have been hampered by dose-limiting toxicity or insufficient clinical benefit, likely due to their lack of specificity. Here, we show that selective inhibition of MMP9 did not induce musculoskeletal syndrome (a characteristic toxicity of pan-MMP inhibitors) in a rat model, but did reduce disease severity in a dextran sodium sulfate-induced mouse model of ulcerative colitis. We also found that MMP9 inhibition decreased tumor growth and metastases incidence in a surgical orthotopic xenograft model of colorectal carcinoma, and that inhibition of either tumor- or stroma-derived MMP9 was sufficient to reduce primary tumor growth. Collectively, these data suggest that selective MMP9 inhibition is a promising therapeutic strategy for treatment of inflammatory and oncology indications in which MMP9 is upregulated and is associated with disease pathology, such as ulcerative colitis and colorectal cancer. In addition, we report the development of a potent and highly selective allosteric MMP9 inhibitor, the humanized monoclonal antibody GS-5745, which can be used to evaluate the therapeutic potential of MMP9 inhibition in patients. PMID:25961845

  15. Pseudomembranous colitis

    MedlinePlus

    Antibiotic-associated colitis; Colitis - pseudomembranous; Necrotizing colitis; C difficile - pseudomembranous ... The C difficile bacteria normally lives in the intestine. However, too much of these bacteria may grow when you ...

  16. Impact of probiotics on toll-like receptor 4 expression in an experimental model of ulcerative colitis.

    PubMed

    Yang, Xia; Fu, Yu; Liu, Jun; Ren, Hong-yu

    2013-10-01

    Toll-like receptors (TLRs) are key components of the innate immune system which trigger antimicrobial host defense responses. This study aimed to investigate the impact of probiotics (Lactobacillus, Bifidobacterium) on the expression of TLR4 and tumor necrosis factor-alpha (TNF-α) in the colon mucosa of rat experimental ulcerative colitis model induced by trinitrobenzene sulfonic acid (TNBS)/ethanol and immune complexes. The gross and histological changes of the colonic mucosa were observed and assessed by the means-standard deviation and independent samples t-test. The protein expression levels of TLR4 and TNF-α were detected by using immunohistochemistry and Western blotting, respectively. It was revealed that there was visible infiltration of inflammatory cells, formation of crypt abscess, and the reduction of goblet cells in the colon tissue of experimental models. As compared with the control group, the levels of TLR4 and TNF-α protein were significantly increased in the model group (P<0.01 for both). No significant difference was found in the expression of TLR4 and TNF-α between the two-week probiotics treatment group and the model group (P>0.05), whereas significant reductions were shown in rats which were treated with probiotics for four weeks as compared with the model group (P<0.01). There was no significant difference between two probiotics-treated groups. Our results implied that probiotics were likely to play a key role in protecting ulcerative colitis by reducing the inflammatory factor TNF-α expression through inhibiting the TLR4 expression in the colon tissue of experimental models.

  17. Anti-inflammatory Efficiency of Ankaferd Blood Stopper in Experimental Distal Colitis Model

    PubMed Central

    Koçak, Erdem; Akbal, Erdem; Taş, Adnan; Köklü, Seyfettin; Karaca, Gökhan; Can, Murat; Kösem, Bahadır; Üstün, Hüseyin

    2013-01-01

    Background/Aim: Ankaferd blood stopper (ABS) is a herbal extract that enhances mucosal healing. In this study, we aimed to investigate the efficiency of ABS in the treatment of experimental distal colitis. Materials and Methods: Twenty one male albino rats were divided into three groups: Sham control (Group 1), colitis induced by acetic acid and treated with saline (Group 2), colitis induced by acetic acid and treated with ABS (Group 3). At end of the 7th day of induction, all the rats were lightly anesthetized with intramuscular ketamine (8 mg/kg) and thereafter laparotomy and total colectomy were performed. The distal colon segment was assessed macroscopically and microscopically. In addition malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) levels of the colonic tissue and changes in body weight were measured. Results: The MDA and NO levels of the colonic tissues and weight loss were significantly higher in Group 2 compared to Group 1 and Group 3. Microscopic and macroscopic damage scores were significantly higher in Group 2 and Group 3 than Group 1 (P: 0.001, P: 0.004, respectively). Although the microscopic and macroscopic damage scores in Group 3 were slightly lower than Group 2, the difference was not statistically significant. The SOD levels of the colonic tissues were not different between the three groups. Conclusion: Weight alterations and high-levels of the colonic tissue MDA and NO suggested that ABS might have anti-inflammatory effects on experimental distal colitis. However, this suggestion was not supported by histopathological findings. PMID:23680710

  18. Sleep deprivation worsens inflammation and delays recovery in a mouse model of colitis

    PubMed Central

    Tang, Yueming; Preuss, Fabian; Turek, Fred W.; Jakate, Shriram; Keshavarzian, Ali

    2012-01-01

    Background and aim We recently showed that patients with inflammatory bowel disease (IBD) report significantly more sleep disturbances. To determine whether disrupted sleep can affect the severity of inflammation and the course of IBD, we used an animal model of colonic inflammation to determine the effects of acute and chronic intermittent sleep deprivation on the severity of colonic inflammation and tissue damage in colitis and recovery from this damage. Methods Acute sleep deprivation (ASD) consisted of 24 h of forced locomotor activity in a mechanical wheel rotating at a constant speed. Chronic intermittent sleep deprivation (CISD) consisted of an acute sleep deprivation episode, followed by additional sleep deprivation periods in the wheel for 6 h every other day throughout the 10 day study period. To induce colitis, mice were given 2% dextran sodium sulfate (DSS) in their daily drinking water for 7 days. The development and severity of colitis were monitored by measuring weight loss and tissue myeloperoxidase (MPO) activity daily and colon histology scores 10 days after initiation of colitis. Results ASD or CISD did not cause colonic inflammation in vehicle-treated mice. Changes in daily body weight, tissue MPO levels and colon histopathology score were similar between mice that were sleep deprived and controls. Daily DSS ingestion caused colitis in mice. ASD worsened colonic inflammation: tissue MPO levels in ASD/DSS-treated mice were significantly higher than in DSS-treated mice that were not sleep deprived. However, the worsening of colonic inflammation by ASD was not enough to exacerbate clinical manifestations of colitis such as weight loss. In contrast, the deleterious effects of CISD were severe enough to cause worsening of histological and clinical manifestations of colitis. The deleterious effects of sleep deprivation on severity of colitis appeared to be due to both increased colonic inflammation and a decrease in the ability of mice to recover from

  19. L-arginine augments the antioxidant effect of garlic against acetic acid-induced ulcerative colitis in rats.

    PubMed

    Harisa, Gamal Eldin I; Abo-Salem, Osama M; El-Sayed, El-Sayed M; Taha, Ehab I; El-Halawany, Nermin

    2009-10-01

    Garlic contains many sulfhydryl compounds that act as antioxidants. However, the role of nitric oxide (NO) in inflammation is controversial. The aim of the present study is to investigate the possible protective effect of garlic against acetic acid-induced ulcerative colitis in rats, as well as the probable modulatory effect of L-arginine (NO precursor) on garlic activity. Intra-rectal inoculation of rats with 4% acetic acid for 3 consecutive days caused a significant increase in the colon weight and marked decrease in the colon length. In addition, acetic acid induced a significant increase in serum levels of nitrate as well as colonic tissue content of malondialdehyde (MDA). Moreover, colonic tissue contents of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were markedly reduced. On the other hand, pre-treatment of rats with garlic (0.25 g/kgbwt, orally) for 4 consecutive weeks and 3 days during induction of colitis significantly reduced the increase in the colon weight induced by acetic acid and ameliorated alterations in oxidant and antioxidant parameters. Interestingly, oral co-administration of garlic (0.25 g/kgbwt) and L-arginine (625 mg/kgbwt) for the same period of garlic administration mitigated the changes in both colon weight and length induced by acetic acid and increased garlic effect on colon tissue contents of MDA and GSH. In conclusion, L-arginine can augment the protective effect of garlic against ulcerative colitis; an effect that might be mainly attributed to its NO donating property resulting in enhancement of garlic antioxidant effect. Further studies will be needed to determine which one of the active ingredients of garlic has the main antioxidant effect to be used with L-arginine. PMID:19783514

  20. Protective effect of Agave americana Linn. leaf extract in acetic acid-induced ulcerative colitis in rats

    PubMed Central

    Mannasaheb, Basheerahmed A.A.; Kulkarni, Preeti V.; Sangreskopp, Mashood Ahmed; Savant, Chetan; Mohan, Anjana

    2015-01-01

    Introduction: Natural plants always provide core compounds for new drug development. In the present life and food style, inflammatory bowel disease has become common and needs a lead compound for its drug development. Aim: To evaluate the effect of Agave americana Linn. leaf extract in acetic acid-induced ulcerative colitis in rats based on its traditional anti-inflammatory use. Materials and Methods: Male Wistar rats were pretreated with A. americana leaf extract in the dose of 200 and 400 mg/kg p.o. daily for 7 days. On 8th day, 2 ml of 4% v/v acetic acid in saline was instilled into rats’ rectum. Prednisolone was used as standard drug and it was administered on the day of acetic acid instillation and continued for 3 days. Extract treatment was continued till 11th day. Body weight, ulcer score, colonic muscle contraction, antioxidant activity and histopathology were studied. Statistical analysis was performed using Parametric one-way analysis of variance followed by Tukey's posttest. Results: A. americana have retained total body weight significantly (P < 0.01) and decreased colon weight/length ratio. Extract have shown a significant decrease (P < 0.001) in ulcer scores, myeloperoxidase, lipid peroxidase activity. Further, extract have shown significant improvement in colonic muscle contraction, histopathology of colon etc., which is comparable with standard drug. Conclusion: A. americana possess protective effect against acetic acid-induced colitis in rats. PMID:26730148

  1. Qingchang Wenzhong Decoction Ameliorates Dextran Sulphate Sodium-Induced Ulcerative Colitis in Rats by Downregulating the IP10/CXCR3 Axis-Mediated Inflammatory Response

    PubMed Central

    Mao, Tang-you; Shi, Rui; Zhao, Wei-han; Guo, Yi; Gao, Kang-li; Chen, Chen; Xie, Tian-hong; Li, Jun-xiang

    2016-01-01

    Qingchang Wenzhong Decoction (QCWZD) is an effective traditional Chinese medicine prescription. Our previous studies have shown that QCWZD has significant efficacy in patients with mild-to-moderate ulcerative colitis (UC) and in colonic mucosa repair in UC rat models. However, the exact underlying mechanism remains unknown. Thus, this study was conducted to determine QCWZD's efficacy and mechanism in dextran sulphate sodium- (DSS-) induced UC rat models, which were established by 7-day administration of 4.5% DSS solution. QCWZD was administered daily for 7 days, after which the rats were euthanized. Disease activity index (DAI), histological score (HS), and myeloperoxidase (MPO) level were determined to evaluate UC severity. Serum interferon gamma-induced protein 10 (IP10) levels were determined using ELISA kits. Western blotting and real-time polymerase chain reaction were, respectively, used to determine colonic protein and gene expression of IP10, chemokine (cys-x-cys motif) receptor (CXCR)3, and nuclear factor- (NF-) κB p65. Intragastric QCWZD administration ameliorated DSS-induced UC, as evidenced by decreased DAI, HS, and MPO levels. Furthermore, QCWZD decreased the protein and gene expression of IP10, CXCR3, and NF-κB p65. Overall, these results suggest that QCWZD ameliorates DSS-induced UC in rats by downregulating the IP10/CXCR3 axis-mediated inflammatory response and may be a novel UC therapy. PMID:27413386

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

    PubMed

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

    2012-01-01

    Male Unib-WH rats were pretreated for two weeks with butanolic (BuOH) and ethyl acetate (EtOAc) fractions. Colitis was induced by rectal administration of TNBS, the treatment continued, and animals were sacrificed on day 7 after the TNBS administration. Phytochemical studies were performed in order to provide the characterization of the tannins present in the bark of R. mangle. Results showed that EtOAc fraction increased the levels of IL-10 (∗∗P < 0.01) and diminished the levels of TNF-α (∗∗∗P < 0.001) and IL-6 (∗∗P < 0.01). BuOH fraction reduced the MPO activity (∗∗P < 0.01) and levels of TBARS (∗∗∗P < 0.001); it also increased COX-1 expression, diminished the levels of TNF-α (∗∗∗P < 0.001), and increased the levels of IL-12 (∗∗∗P < 0.001). Besides, both treatments augmented the levels of GSH (∗P < 0.05), the activity of GSH-Px (∗∗P < 0.01 for BuOH fraction and ∗∗∗P < 0.001 for EtOAc fraction), and CAT (∗∗P < 0.01). In conclusion, both treatments ameliorated the injury induced by TNBS through different mechanisms, probably by their chemical composition which directed its activity into an antioxidant or anti-inflammatory response, leading to an immune modulation. PMID:23056142

  3. Protective effect of naringenin on acetic acid-induced ulcerative colitis in rats

    PubMed Central

    Al-Rejaie, Salim S; Abuohashish, Hatem M; Al-Enazi, Maher M; Al-Assaf, Abdullah H; Parmar, Mihir Y; Ahmed, Mohammed M

    2013-01-01

    AIM: To evaluate the ameliorative effect of naringenin (NG) during ulcerative colitis (UC) in rats. METHODS: Rats were treated with three different doses (25, 50 and 100 mg/kg per day) of NG and a single dose of mesalazine (MES, 300 mg/kg per day) for seven days prior to ulcerative colitis induction by 4% acetic acid (AA). Twenty four hours after AA rectal administration, animals were scarified and the colonic tissues were dissected. Colonic mucus content was estimated using Alcian blue dye binding technique. In colon tissues, levels of total glutathione sulphadryls (T-GSH), non-protein sulphadryls (NP-SH) and thiobarbituric acid reactive substances (TBARS) were evaluated. The activities of the antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD) were measured. Concentrations of nucleic acids (DNA and RNA) and total protein were also estimated in colon tissues. Colonic levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and nitric oxide (NO) were estimated. In cross section of colitis tissue the histopathological changes were observed. RESULTS: Colonic mucus content was decreased in AA compared to controls (587.09 ± 65.59 mg/kg vs 941.78 ± 68.41 mg/kg, P < 0.001). AA administration markedly reduced T-GSH (5.25 ± 0.37 nmol/L vs 3.04 ± 0.24 nmol/L, P < 0.01), NP-SH (3.16 ± 0.04 nmol/L vs 2.16 ± 0.30 nmol/L, P < 0.01), CAT (6.77 ± 0.40 U/mg vs 3.04 ± 0.2 U/mg, P < 0.01) and SOD (3.10 ± 0.11 U/mg vs 1.77 ± 0.18 U/mg, P < 0.01) while TBARS, TNF-α, IL-1β, IL-6, PGE2 and NO levels (15.09 ± 3.84 nmol/L vs 59.90 ± 16.34 nmol/L, P < 0.01; 113.56 ± 1.91 pg/mg vs 134.24 ± 4.77 pg/mg, P < 0.01; 209.20 ± 36.38 pg/mg vs 422.19 ± 31.47 pg/mg, P < 0.01; 250.83 ± 25.09 pg/mg vs 638.58 ± 115.9 pg/mg, P < 0.01; 248.19 ± 36.98 pg/mg vs 541.74 ± 58.34 pg/mg, P < 0.01 and 81.26 ± 2.98 mmol/g vs 101.90 ± 10.73 mmol/g, P < 0.001) were increased in colon of rats with UC compared controls

  4. St. John's wort may ameliorate 2,4,6-trinitrobenzenesulfonic acid colitis off rats through the induction of pregnane X receptors and/or P-glycoproteins.

    PubMed

    Sehirli, A O; Cetinel, S; Ozkan, N; Selman, S; Tetik, S; Yuksel, M; Dulger, F G A

    2015-04-01

    It is reported that deficiencies of the pregnane X receptor (PXR) and P-glycoprotein (P-gp), the latter of which is encoded by the MDR1 gene, are important factors in the pathogenesis of inflammatory bowel disease (IBD). It is also known that the activation of PXR is protective of IBD due to the mutual repression between PXR and nuclear factor kappa B (NF-κB) expression and because NF-κB was reported to play a pivotal role in the pathogenesis of ulcerative colitis. The goal of this study was to investigate whether St. John's wort (SJW) and spironolactone (SPL), both known to have strong inducing effects on cytochrome P 450 (CYP) enzymes as well as PXR and P-gp, have ameliorating effects on 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis of rats through induction of PXR and/or P-gp. Wistar albino rats (250 - 300 g) were divided into control and TNBS-colitis groups. Each group was then divided into a) control (saline), b) SJW (300 mg/kg p.o. bid), and c) SPL (80 mg/kg p.o.) groups. Drugs were given for 7 days. Both treatments ameliorated the clinical hallmarks of colitis, as determined by body weight loss and assessment of diarrhea, colon length, and bowel histology. Plasma levels of NF-κB, tumour necrosis factor-alpha (TNF-α) and tissue myeloperoxidase (MPO) activity, as well as the oxidative stress markers that increased during colitis, decreased significantly after both treatments. The PXR and P-gp expression in the intestinal tissues was diminished in the colitis group but increased after drug treatments. Both drugs appeared to have significant antioxidant and anti-inflammatory effects and ameliorated the TNBS colitis of the rats, most likely through their PXR- and P-gp-inducing properties.

  5. T cell transfer model of colitis: a great tool to assess the contribution of T cells in chronic intestinal inflammation.

    PubMed

    Eri, Rajaraman; McGuckin, Michael A; Wadley, Robert

    2012-01-01

    Inflammatory bowel diseases (IBD) consist of Crohn's disease (CD) and ulcerative colitis (UC) affecting about 0.1% of the western population. These two chronic gut diseases affect youth at their prime of life causing diarrhoea, intestinal bleeding, and severe gut discomfort. Mouse models of colitis have been major tools in understanding the pathogenesis of IBD. A number of mouse models are available to assess the contribution of T cells in the pathogenesis of CD and UC. Among these, the T cell transfer model of colitis is the most widely used model to dissect the initiation, induction, and regulation of immunopathology in chronic colitis mediated by T cells. The methodology below describes the classification of various animal models and explains the T cell transfer model in detail, including flow cytometry-based isolation of naïve T cells that are used in the transfer, immunological concepts, detailed immune-pathological assessment, shortcomings of the model, and the latest improvements to this colitis model. A special focus is paid to the utilisation of the T cell transfer model in delineating the immunopathology in a primary epithelial defect model of colitis, namely Winnie. PMID:22262449

  6. Restoration of the integrity of rat caeco-colonic mucosa by resistant starch, but not by fructo-oligosaccharides, in dextran sulfate sodium-induced experimental colitis.

    PubMed

    Moreau, Noëlle M; Martin, Lucile J; Toquet, Claire S; Laboisse, Christian L; Nguyen, Patrick G; Siliart, Brigitte S; Dumon, Henri J; Champ, Martine M J

    2003-07-01

    Butyrate is recognised as efficient in healing colonic inflammation, but cannot be used as a long-term treatment. Dietary fibre that produces a high-butyrate level when fermented represents a promising alternative. We hypothesised that different types of dietary fibre do not have the same efficiency of healing and that this could be correlated to their fermentation characteristics. We compared short-chain fructo-oligosaccharides (FOS) and type 3 resistant starch (RS) in a previously described dextran sulfate sodium (DSS)-induced colitis model. Seventy-two Sprague-Dawley rats received water (control rats) or DSS (50 g DSS/l for 7 d then 30 g DSS/l for 7 (day 7) or 14 (day 14) d). The rats were fed a basal diet (BD), or a FOS or RS diet creating six groups: BD-control, BD-DSS, FOS-control, FOS-DSS, RS-control and RS-DSS. Caeco-colonic inflammatory injuries were assessed macroscopically and histologically. Short-chain fatty acids (SCFA) were quantified in caeco-colon, portal vein and abdominal aorta. At days 7 and 14, caecal and distal macroscopic and histological observations were improved in RS-DSS compared with BD-DSS and also with FOS-DSS rats. Caeco-colonic SCFA were reduced in FOS-DSS and RS-DSS groups compared with healthy controls. The amount of butyrate was higher in the caecum of the RS-DSS rats than in the BD-DSS and FOS-DSS rats, whereas distal butyrate was higher in FOS-DSS rats. Partially explained by higher luminal levels of SCFA, especially butyrate, the healing effect of RS confirms the involvement of some types of dietary fibre in inflammatory bowel disease. Moreover, the ineffectiveness of FOS underlines the importance of the type of dietary substrate.

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

    PubMed Central

    Osman, Nadia; Adawi, Diya; Molin, Göran; Ahrne, Siv; Berggren, Anna; Jeppsson, Bengt

    2006-01-01

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

  8. Synergic Interaction of Rifaximin and Mutaflor (Escherichia coli Nissle 1917) in the Treatment of Acetic Acid-Induced Colitis in Rats.

    PubMed

    Dembiński, Artur; Warzecha, Zygmunt; Ceranowicz, Piotr; Dembiński, Marcin; Cieszkowski, Jakub; Gosiewski, Tomasz; Bulanda, Małgorzata; Kuśnierz-Cabala, Beata; Gałązka, Krystyna; Konturek, Peter Christopher

    2016-01-01

    Background. Inflammatory bowel disease results from the dysregulation of immune response to environmental and microbial agents in genetically susceptible individuals. The aim of the present study was to examine the effect of rifaximin and/or Mutaflor (Escherichia coli Nissle 1917, EcN) administration on the healing of acetic acid-induced colitis. Methods. Colitis was induced in male Wistar rats by rectal enema with 3.5% acetic acid solution. Rifaximin (50 mg/kg/dose) and/or Mutaflor (10(9) CFU/dose) were given intragastrically once a day. The severity of colitis was assessed at the 8th day after induction of inflammation. Results. Treatment with rifaximin significantly accelerated the healing of colonic damage. This effect was associated with significant reversion of the acetic acid-evoked decrease in mucosal blood flow and DNA synthesis. Moreover, administration of rifaximin significantly reduced concentration of proinflammatory TNF-α and activity of myeloperoxidase in colonic mucosa. Mutaflor given alone was without significant effect on activity of colitis. In contrast, Mutaflor given in combination with rifaximin significantly enhanced therapeutic effect of rifaximin. Moreover, Mutaflor led to settle of the colon by EcN and this effect was augmented by pretreatment with rifaximin. Conclusion. Rifaximin and Mutaflor exhibit synergic anti-inflammatory and therapeutic effect in acetic acid-induced colitis in rats. PMID:27433160

  9. Synergic Interaction of Rifaximin and Mutaflor (Escherichia coli Nissle 1917) in the Treatment of Acetic Acid-Induced Colitis in Rats

    PubMed Central

    Warzecha, Zygmunt; Ceranowicz, Piotr; Dembiński, Marcin; Cieszkowski, Jakub; Bulanda, Małgorzata; Kuśnierz-Cabala, Beata; Gałązka, Krystyna; Konturek, Peter Christopher

    2016-01-01

    Background. Inflammatory bowel disease results from the dysregulation of immune response to environmental and microbial agents in genetically susceptible individuals. The aim of the present study was to examine the effect of rifaximin and/or Mutaflor (Escherichia coli Nissle 1917, EcN) administration on the healing of acetic acid-induced colitis. Methods. Colitis was induced in male Wistar rats by rectal enema with 3.5% acetic acid solution. Rifaximin (50 mg/kg/dose) and/or Mutaflor (109 CFU/dose) were given intragastrically once a day. The severity of colitis was assessed at the 8th day after induction of inflammation. Results. Treatment with rifaximin significantly accelerated the healing of colonic damage. This effect was associated with significant reversion of the acetic acid-evoked decrease in mucosal blood flow and DNA synthesis. Moreover, administration of rifaximin significantly reduced concentration of proinflammatory TNF-α and activity of myeloperoxidase in colonic mucosa. Mutaflor given alone was without significant effect on activity of colitis. In contrast, Mutaflor given in combination with rifaximin significantly enhanced therapeutic effect of rifaximin. Moreover, Mutaflor led to settle of the colon by EcN and this effect was augmented by pretreatment with rifaximin. Conclusion. Rifaximin and Mutaflor exhibit synergic anti-inflammatory and therapeutic effect in acetic acid-induced colitis in rats. PMID:27433160

  10. Chronic administration of galanin attenuates the TNBS-induced colitis in rats.

    PubMed

    Talero, E; Sánchez-Fidalgo, S; Calvo, J R; Motilva, V

    2007-06-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disorder considered as a consequence of an aberrant response of the immune system to luminal antigens. Numerous groups of agents are being evaluated as novel therapeutic approaches for its treatment; in this way, different peptides have emerged as potential candidates. Galanin is an active neuropeptide distributed in the central and periphery nervous systems although it has been also described having important autocrine and paracrine regulatory capacities with interesting inflammatory and immune properties. In this line, we have observed that galanin treatment has a significant preventive effect in the experimental trinitrobenzensulfonic acid (TNBS) acute model of inflammatory colitis. The aim of the present study was to investigate intensively the role played by the peptide in the evolution of the inflammatory pathology associated to IBD. Galanin (5 and 10 microg/kg/day) was administered i.p., daily, starting 24 h after TNBS instillation, and continuing for 14 and 21 days. The lesions were blindly scored according to macroscopic and histological analyses and quantified as ulcer index. The results demonstrated that chronic administration of galanin improved the colon injury than the TNBS induced. The study by Western-blotting of the expression of nitric oxide inducible enzyme (iNOS), as well as the total nitrite production (NO) assayed by Griess-reaction, showed significant reduction associated with peptide administration. The number of mast cells was also identified in histological preparations stained with toluidine blue and the results showed that samples from galanin treatment, mostly at 21 days, had increased the number of these cells and many of them had a degranulated feature. In conclusion, chronic administration of galanin is able to exert a beneficial effect in the animal model of IBD assayed improving the reparative process. Participation of nitric oxide pathways and mucosal mast cells

  11. Rivastigmine Alleviates Experimentally Induced Colitis in Mice and Rats by Acting at Central and Peripheral Sites to Modulate Immune Responses

    PubMed Central

    Shifrin, Helena; Nadler-Milbauer, Mirela; Shoham, Shai; Weinstock, Marta

    2013-01-01

    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 and in

  12. The anti-ulcerative colitis effects of Annona squamosa Linn. leaf aqueous extract in experimental animal model

    PubMed Central

    Ibrahim, Rasha YM; Hassan, Amal I; AL-Adham, Eithar K

    2015-01-01

    This study aimed to evaluate the anti-inflammatory effects of Annona squamosa (A. squamosa) leaf aqueous extract against acetic acid induced colitis in rats with a trial to explore its use for the treatment of colon inflammation. Sprague Dawley rats weighing 180-200 g were used in this study. Treatment with A. squamosa extract at dose 300 mg/kg for 4 weeks counteracted acetic acid induced ulcerative colitis by a significant decrease (P<0.05) of colonic tissue of malondialdehyde (MDA) and significant increases of catalase (CAT), glutathione (GSH) and glutathione peroxidase (Gpx) compared to ulcerative colitis control group. Furthermore, induction of oxidative stress was observed in the colonic tissue through the levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG) which significant increase in colonic tissue DNA by acetic acid. Moreover AA induced significant increase in serum interleukin-10 (IL10), tumor necrosis factor-α (TNF-α), transforming growth factor (TGF 1β), and C reactive protein (CRP) as compared to the control group. On the contrary, our results showed AA induced significant decrease of vascular endothelial growth factor (VEGF) and thyroid hormones triiodothyronin and thyroxin (T3 & T4) in installed group with AA as compared to control which significantly improved after treatment with A. squamosa leaf extract. Histopathological observation in our study confirmed the biochemical study. Thus, therapeutic method offer a sign to analyze further the effectiveness of A. squamosa as a unique agent for alleviating colitis. PMID:26885156

  13. The Attenuation of Scutellariae radix Extract on Oxidative Stress for Colon Injury in Lipopolysaccharide-induced RAW264.7 Cell and 2,4,6-trinitrobenzene Sulfonic Acid-induced Ulcerative Colitis Rats

    PubMed Central

    Jin, Yu; Yang, Jun; Lin, Lianjie; Lin, Yan; Zheng, Changqing

    2016-01-01

    Background: Oxidative stress (OS) has been regarded as one of the major pathogeneses of ulcerative colitis (UC) through damaging colon. It has been shown that Scutellariae radix (SR) extract has a beneficial effect for the prevention and treatment of UC. Objective: The aim of this study was to investigate whether SR had a potential capacity on oxidant damage for colon injury both in vivo and in vitro. Materials and Methods: The 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to induce UC rats model while 1 μg/ml lipopolysaccharide (LPS) was for RAW264.7 cell damage. Disease activity index (DAI) was determined to response the severity of colitis. The myeloperoxidase (MPO) activity in rat colon was also estimated. The 2,2’-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid assay was performed to evaluate the total antioxidant capacity of SR. Furthermore, the activity of glutathione peroxidase (GSH-PX), catalase (CAT), superoxide dismutase (SOD), and lipid peroxidation malondialdehyde (MDA) in cell supernatant and rat serum were detected by appropriate kits. In addition, an immunohistochemical assay was applied to examine transforming growth factor beta 1 (TGF-β1) protein expression in colon tissue. Results: The treatment with SR could significantly increase the activity of GSH-PX, CAT, and SOD associated with OS in LPS-induced RAW264.7 cell damage and TNBS-induced UC rats. However, the level of MDA was markedly reduced both in vitro and in vivo. Furthermore, SR significantly decreased DAI and reversed the increased MPO activity. Thus, SR could decrease the severity of acute TNBS-induced colitis in rats. Immunohistochemical assay showed that SR significantly downregulated TGF-β1 protein expression in colon tissue. Conclusion: Our data provided evidence to support this fact that SR attenuated OS in LPS-induced RAW264.7 cell and also in TNBS-induced UC rats. Thus, SR may be an interesting candidate drug for the management of UC. SUMMARY Scutellariae radix (SR

  14. Animal models of ulcerative colitis and their application in drug research

    PubMed Central

    Low, Daren; Nguyen, Deanna D; Mizoguchi, Emiko

    2013-01-01

    The specific pathogenesis underlying inflammatory bowel disease is complex, and it is even more difficult to decipher the pathophysiology to explain for the similarities and differences between two of its major subtypes, Crohn’s disease and ulcerative colitis (UC). Animal models are indispensable to pry into mechanistic details that will facilitate better preclinical drug/therapy design to target specific components involved in the disease pathogenesis. This review focuses on common animal models that are particularly useful for the study of UC and its therapeutic strategy. Recent reports of the latest compounds, therapeutic strategies, and approaches tested on UC animal models are also discussed. PMID:24250223

  15. Green Tea Polyphenols and Sulfasalazine have Parallel Anti-Inflammatory Properties in Colitis Models

    PubMed Central

    Oz, Helieh S.; Chen, Theresa; de Villiers, Willem J.S.

    2013-01-01

    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. IL-10 deficient animals became moribund on high dose, while tolerated low and Mid doses with significant improved symptoms of 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 (twofold). EGCG additionally reduced leptin levels (p < 0.01) while GrTP and sulfasalazine had no effect on

  16. Anti-inflammatory effect of volatile oil and hydroalcoholic extract of Rosa damascena Mill. on acetic acid-induced colitis in rats

    PubMed Central

    Latifi, Ghazal; Ghannadi, Alireza; Minaiyan, Mohsen

    2015-01-01

    Rosa damascena is a small plant belonging to Rosaceae family which has been used for the treatment of some inflammatory diseases and digestive disorders in the Iranian folk medicine. This study was performed to investigate the effect of R. damascena hydroalcoholic extract (RDHE) and R. damascena volatile oil (RDVO) on ulcerative colitis induced by acetic acid in rats. Different doses of RDHE (250, 500, 1000 mg/kg) and RDVO (100, 200, 400 µl/kg) were given orally (p.o.) and doses of RDHE (125, 250, 500 mg/kg) were administrated intraperitoneally (i.p.) to the male Wistar rats (n=6) 2 h before induction of colitis which continued daily for 4 successive days. Prednisolone (4 mg/kg p.o.) and dexamethasone (1 mg/kg i.p.) were used in the reference groups. Weight/length ratios of wet colon were measured and the tissues were assessed macroscopically, histopathologically, and biochemically via measuring the myeloperoxidase (MPO) activity. Oral RDHE at all doses examined, and the lowest dose of RDVO given p.o. or RDHE administered i.p. reduced all indices of colitis measured in different assays as well as the MPO activity. These results provide encouraging support for the use of hydroalcoholic extract of R. damascena in relieving alimentary inflammatory conditions and reinforce the use of this plant to develop new agents for treating ulcerative colitis. PMID:26779271

  17. Time to Integrate to Nest Test Evaluation in a Mouse DSS-Colitis Model

    PubMed Central

    Häger, Christine; Keubler, Lydia M.; Biernot, Svenja; Dietrich, Jana; Buchheister, Stephanie; Buettner, Manuela; Bleich, André

    2015-01-01

    Severity assessment in laboratory animals is an important issue regarding the implementation of the 3R concept into biomedical research and pivotal in current EU regulations. In mouse models of inflammatory bowel disease severity assessment is usually undertaken by clinical scoring, especially by monitoring reduction of body weight. This requires daily observance and handling of each mouse, which is time consuming, stressful for the animal and necessitates an experienced observer. The time to integrate to nest test (TINT) is an easily applicable test detecting disturbed welfare by measuring the time interval mice need to integrate nesting material to an existing nest. Here, TINT was utilized to assess severity in a mouse DSS-colitis model. TINT results depended on the group size of mice maintained per cage with most consistent time intervals measured when co-housing 4 to 5 mice. Colitis was induced with 1% or 1.5% DSS in group-housed WT and Cd14-deficient mice. Higher clinical scores and loss of body weight were detected in 1.5% compared to 1% DSS treated mice. TINT time intervals showed no dose dependent differences. However, increased clinical scores, body weight reductions, and increased TINT time intervals were detected in Cd14-/- compared to WT mice revealing mouse strain related differences. Therefore, TINT is an easily applicable method for severity assessment in a mouse colitis model detecting CD14 related differences, but not dose dependent differences. As TINT revealed most consistent results in group-housed mice, we recommend utilization as an additional method substituting clinical monitoring of the individual mouse. PMID:26637175

  18. Dextran sulfate sodium-induced colitis-associated neoplasia: a promising model for the development of chemopreventive interventions.

    PubMed

    Clapper, Margie Lee; Cooper, Harry Stanley; Chang, Wen-Chi Lee

    2007-09-01

    Individuals diagnosed with ulcerative colitis face a significantly increased risk of developing colorectal dysplasia and cancer during their lifetime. To date, little attention has been given to the development of a chemopreventive intervention for this high-risk population. The mouse model of dextran sulfate sodium (DSS) - induced colitis represents an excellent preclinical system in which to both characterize the molecular events required for tumor formation in the presence of inflammation and assess the ability of select agents to inhibit this process. Cyclic administration of DSS in drinking water results in the establishment of chronic colitis and the development of colorectal dysplasias and cancers with pathological features that resemble those of human colitis-associated neoplasia. The incidence and multiplicity of lesions observed varies depending on the mouse strain used (ie, Swiss Webster, C57BL/6J, CBA, ICR) and the dose (0.7%-5.0%) and schedule (1-15 cycles with or without a subsequent recovery period) of DSS. The incidence of neoplasia can be increased and its progression to invasive cancer accelerated significantly by administering DSS in combination with a known colon carcinogen (azoxymethane (AOM), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-1- methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)) or iron. More recent induction of colitis-associated neoplasia in genetically defined mouse strains has provided new insight into the role of specific genes (ie, adenomatous polyposis coli (Apc), p53, inducible nitric oxide synthase (iNOS), Msh2) in the development of colitis-associated neoplasias. Emerging data from chemopreventive intervention studies document the efficacy of several agents in inhibiting DSS-induced neoplasia and provide great promise that colitis-associated colorectal neoplasia is a preventable disease.

  19. Protective Effect of Dietary Lily Bulb on Dextran Sulfate Sodium-Induced Colitis in Rats Fed a High-Fat Diet.

    PubMed

    Okazaki, Yukako; Chiji, Hideyuki; Kato, Norihisa

    2016-01-01

    Lily bulb is traditionally consumed in East Asia and contains high amounts of glucomannan. This study investigated the effect of dietary lily bulb on dextran sulfate sodium (DSS)-induced colitis in rats fed a high-fat (HF) diet. Male Sprague-Dawley rats were fed a diet containing 30% beef tallow with or without 7% steamed lily bulb powder for 17 d. Experimental colitis was induced by replacing drinking water with DSS during the last 7 d. The disease activity index (DAI) was significantly lower in the lily bulb+DSS group than in the DSS group on day 17. The fecal abundance of Bifidobacterium was significantly reduced in the DSS group compared with that in the control group, but it was recovered by lily bulb intake. Cecal butyrate, fecal mucins, and alkaline phosphatase (ALP) activity were significantly higher in the DSS group than in the control group. Dietary lily bulb potentiated the increase in cecal butyrate, fecal mucins, and the ALP activity caused by DSS treatment. These results indicate that lily bulb attenuates DSS-induced colitis by modulating colonic microflora, organic acids, mucins, and ALP activity in HF diet-fed rats. PMID:27465728

  20. Augmented activity of the pelvic nerve afferent mediated by TRP channels in dextran sulfate sodium (DSS)-induced colitis of rats.

    PubMed

    Makimura, Yukitoshi; Ito, Koichi; Kuwahara, Masayoshi; Tsubone, Hirokazu

    2012-08-01

    Enteritis has been recognized as a major symptom in domestic animals and human patients suffering from feed and food poisonings. The aim of the present study was to clarify the excitatory mechanism of the pelvic nerve afferent which may influence the occurrence of enteritis in response to nociceptive chemical stimuli of the colon in normal and abnormal rats with colitis induced by dextran sulfate sodium (DSS). The pelvic nerve afferent activity was markedly increased by colonic instillation of solution (0.5 ml) of acetic acid (5-25%) and capsaicin (100 μg/ml). The nerve activity was augmented by colonic instillation of capsaicin to a greater extent in rats with DSS-induced colitis than in normal control rats. This augmented activity by capsaicin was more prominent at one day (DSS-1) than at 8 day (DSS-8) after the administration of DSS. The increased nerve activity caused by capsaicin in DSS-1 and DSS-8 was significantly inhibited by pretreatment with ruthenium red, which is a nonselective inhibitor of TRP channels of unmyelinated C-fibers (nociceptors). In conclusion, it was elucidated that the nociceptive function of the pelvic nerve was largely elevated at one day after DSS-induced colitis and such increased function was mostly mediated by TRP channels.

  1. Protective Effect of Dietary Lily Bulb on Dextran Sulfate Sodium-Induced Colitis in Rats Fed a High-Fat Diet.

    PubMed

    Okazaki, Yukako; Chiji, Hideyuki; Kato, Norihisa

    2016-01-01

    Lily bulb is traditionally consumed in East Asia and contains high amounts of glucomannan. This study investigated the effect of dietary lily bulb on dextran sulfate sodium (DSS)-induced colitis in rats fed a high-fat (HF) diet. Male Sprague-Dawley rats were fed a diet containing 30% beef tallow with or without 7% steamed lily bulb powder for 17 d. Experimental colitis was induced by replacing drinking water with DSS during the last 7 d. The disease activity index (DAI) was significantly lower in the lily bulb+DSS group than in the DSS group on day 17. The fecal abundance of Bifidobacterium was significantly reduced in the DSS group compared with that in the control group, but it was recovered by lily bulb intake. Cecal butyrate, fecal mucins, and alkaline phosphatase (ALP) activity were significantly higher in the DSS group than in the control group. Dietary lily bulb potentiated the increase in cecal butyrate, fecal mucins, and the ALP activity caused by DSS treatment. These results indicate that lily bulb attenuates DSS-induced colitis by modulating colonic microflora, organic acids, mucins, and ALP activity in HF diet-fed rats.

  2. Selecting lactic acid bacteria for their safety and functionality by use of a mouse colitis model.

    PubMed

    Daniel, Catherine; Poiret, Sabine; Goudercourt, Denise; Dennin, Veronique; Leyer, Gregory; Pot, Bruno

    2006-09-01

    Studies showed that specific probiotics might provide therapeutic benefits in inflammatory bowel disease. However, a rigorous screening of new probiotics is needed to study possible adverse interactions with the host, particularly when intended for administration to individuals with certain health risks. In this context, the objective of this study was to investigate the role of three lactobacilli (LAB) on intestinal inflammation and bacterial translocation using variations of the mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis. We first compared the in vitro ability of LAB to survive gastrointestinal tract (GIT) conditions and their ability to persist in the GIT of mice following daily oral administration. As a control, we included a nonprobiotic Lactobacillus paracasei strain, previously isolated from an endocarditis patient. Feeding high doses of LAB strains to healthy and to TNBS-treated mice did not induce any detrimental effect or abnormal translocation of the bacteria. Oral administration of Lactobacillus salivarius Ls-33 had a significant preventive effect on colitis in mice, while Lactobacillus plantarum Lp-115 and Lactobacillus acidophilus NCFM did not. None of the three selected LAB strains translocated to extraintestinal organs of TNBS-treated mice. In contrast, L. paracasei exacerbated colitis under severe inflammatory conditions and translocated to extraintestinal organs. This study showed that evaluations of the safety and functionality of new probiotics are recommended. We conclude that not all lactobacilli have similar effects on intestinal inflammation and that selected probiotics such as L. salivarius Ls-33 may be considered in the prevention or treatment of intestinal inflammation.

  3. Selecting Lactic Acid Bacteria for Their Safety and Functionality by Use of a Mouse Colitis Model

    PubMed Central

    Daniel, Catherine; Poiret, Sabine; Goudercourt, Denise; Dennin, Veronique; Leyer, Gregory; Pot, Bruno

    2006-01-01

    Studies showed that specific probiotics might provide therapeutic benefits in inflammatory bowel disease. However, a rigorous screening of new probiotics is needed to study possible adverse interactions with the host, particularly when intended for administration to individuals with certain health risks. In this context, the objective of this study was to investigate the role of three lactobacilli (LAB) on intestinal inflammation and bacterial translocation using variations of the mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis. We first compared the in vitro ability of LAB to survive gastrointestinal tract (GIT) conditions and their ability to persist in the GIT of mice following daily oral administration. As a control, we included a nonprobiotic Lactobacillus paracasei strain, previously isolated from an endocarditis patient. Feeding high doses of LAB strains to healthy and to TNBS-treated mice did not induce any detrimental effect or abnormal translocation of the bacteria. Oral administration of Lactobacillus salivarius Ls-33 had a significant preventive effect on colitis in mice, while Lactobacillus plantarum Lp-115 and Lactobacillus acidophilus NCFM did not. None of the three selected LAB strains translocated to extraintestinal organs of TNBS-treated mice. In contrast, L. paracasei exacerbated colitis under severe inflammatory conditions and translocated to extraintestinal organs. This study showed that evaluations of the safety and functionality of new probiotics are recommended. We conclude that not all lactobacilli have similar effects on intestinal inflammation and that selected probiotics such as L. salivarius Ls-33 may be considered in the prevention or treatment of intestinal inflammation. PMID:16957197

  4. Ligands for peroxisome proliferator-activated receptors alpha and gamma inhibit chemically induced colitis and formation of aberrant crypt foci in rats.

    PubMed

    Tanaka, T; Kohno, H; Yoshitani, S; Takashima, S; Okumura, A; Murakami, A; Hosokawa, M

    2001-03-15

    The biological role of the peroxisome proliferator-activated receptors (PPARs) in various diseases, including inflammation and cancer, has been highlighted recently. Although PPARgamma ligands have been found to inhibit mammary carcinogenesis in rodents, the effects on colon tumorigenesis are controversial. In the present study, three different experiments were conducted to investigate the modifying effects of PPARs ligands (PPARalpha and PPARgamma) on colitis and an early phase of colitis-related colon carcinogenesis in male F344 rats. In the first experiment, gastric gavage of troglitazone (PPARgamma ligand, 10 or 100 mg/kg body weight) or bezafibrate (PPARalpha ligand, 10 or 100 mg/kg body weight) inhibited colitis induced by dextran sodium sulfate (DSS) and lowered trefoil factor-2 content in colonic mucosa. In the second experiment, dietary administration (0.01 or 0.05% in diet) of troglitazone and bezafibrate for 4 weeks significantly reduced azoxymethane (AOM, two weekly s.c. injections, 20 mg/kg body weight)-induced formation of aberrant crypts foci, which are precursor lesions for colon carcinoma. In the third experiment, dietary administration (0.01% in diet for 6 weeks) of pioglitazone (PPARgamma ligand), troglitazone, and bezafibrate effectively suppressed DSS/AOM-induced ACF. Administration of both ligands significantly reduced cell proliferation activity in colonic mucosa exposed to DSS and AOM. Our results suggest that synthetic PPARs ligands (PPARalpha and PPARgamma) can inhibit the early stages of colon tumorigenesis with or without colitis.

  5. Murine Trinitrobenzoic Acid-Induced Colitis as a Model of Crohn's Disease.

    PubMed

    Kuemmerle, John F

    2016-01-01

    Inflammatory Bowel Diseases, Crohn's disease and ulcerative colitis, result from the uncontrolled inflammation that occurs in genetically susceptible individuals and the dysregulation of the innate and adaptive immune systems. The response of these immune systems to luminal gut microbiota and their products results in altered intestinal permeability, loss of barrier function, and mucosal inflammation and ulceration. Animal models of experiment intestinal inflammation have been developed that leverage the development of spontaneous inflammation in certain mouse strains, e.g. Samp1/Yit mice, or induction of inflammation using gene-targeting e.g. IL-10 null mice, administration of exogenous agents e.g. DSS, or adoptive transfer of T-cells into immunodeficient mice, e.g. CD4(+) CD45Rb(Hi) T-cell transfer. Colitis induced by rectal instillation of the haptenizing agent, 2,4,6 trinitrobenzene sulfonic acid, is one of the most commonly used and well-characterized models of Crohn's disease in humans. PMID:27246038

  6. Treatment with novel AP-1 and NF-κB inhibitors restores the colonic endocrine cells to normal levels in rats with DSS-induced colitis

    PubMed Central

    EL-SALHY, MAGDY; UMEZAWA, KAZUO

    2016-01-01

    The aim of this study was to determine the effects of two anti-inflammatory agents on the abnormalities in colonic endocrine cells in dextran sodium sulfate (DSS)-induced colitis. Colitis was induced in male Wistar rats (n=45) using DSS; a further 15 rats without colitis were included in a healthy control group. The animals with DSS-induced colitis were randomly divided into 3 treatment groups as follows: i) DSS group, rats were treated with 0.5 ml of 0.5% carboxymethyl cellulose (CMC); ii) DSS-G group, rats were treated with 3-[(dodecyl thiocarbonyl)-methyl]-glutarimide (DTCM-G), a novel activator protein 1 (AP-1) inhibitor, 20 mg/kg in CMC; and iii) DSS-Q group, rats were treated with dehydroxymethylepoxyquinomicin, a nuclear factor κB (NF-κB) inhibitor, 15 mg/kg in CMC. The treatments were administered intraperitoneally, twice daily for 5 days, after which the animals were sacrificed and tissue samples from the colon were immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), enteroglucagon, pancreatic polypeptide (PP), somatostatin, leukocytes, B/T lymphocytes, B lymphocytes, T lymphocytes, macrophages/monocytes and mast cells. The densities of these endocrine and immune cells were quantified by computer-aided image analysis. The densities of CgA-, serotonin-, PYY- and enteroglucagon-producing cells were significantly higher, and those of PP- and somatostatin-producing cells were significantly lower in the DSS-G, DSS-Q and control groups than in the DSS group. The densities of all the immune cells were lower in the DSS-G, DSS-Q and control groups than in the DSS group. The densities of all endocrine cell types and immune cells in both the DSS groups treated with anti-inflammatory agents were restored to control levels. In conclusion, our data demonstrate that there is an interaction between endocrine and immune cells during inflammation. This interaction with subsequent changes in endocrine cells is responsible for the clinical manifestation of

  7. Treatment with novel AP-1 and NF-κB inhibitors restores the colonic endocrine cells to normal levels in rats with DSS-induced colitis.

    PubMed

    El-Salhy, Magdy; Umezawa, Kazuo

    2016-03-01

    The aim of this study was to determine the effects of two anti-inflammatory agents on the abnormalities in colonic endocrine cells in dextran sodium sulfate (DSS)-induced colitis. Colitis was induced in male Wistar rats (n=45) using DSS; a further 15 rats without colitis were included in a healthy control group. The animals with DSS-induced colitis were randomly divided into 3 treatment groups as follows: i) DSS group, rats were treated with 0.5 ml of 0.5% carboxymethyl cellulose (CMC); ii) DSS‑G group, rats were treated with 3-[(dodecylthiocarbonyl)‑methyl]‑glutarimide (DTCM‑G), a novel activator protein 1 (AP-1) inhibitor, 20 mg/kg in CMC; and iii) DSS‑Q group, rats were treated with dehydroxymethylepoxyquinomicin, a nuclear factor κB (NF-κB) inhibitor, 15 mg/kg in CMC. The treatments were administered intraperitoneally, twice daily for 5 days, after which the animals were sacrificed and tissue samples from the colon were immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), enteroglucagon, pancreatic polypeptide (PP), somatostatin, leukocytes, B/T lymphocytes, B lymphocytes, T lymphocytes, macrophages/monocytes and mast cells. The densities of these endocrine and immune cells were quantified by computer‑aided image analysis. The densities of CgA-, serotonin-, PYY- and enteroglucagon-producing cells were significantly higher, and those of PP- and somatostatin-producing cells were significantly lower in the DSS‑G, DSS‑Q and control groups than in the DSS group. The densities of all the immune cells were lower in the DSS‑G, DSS‑Q and control groups than in the DSS group. The densities of all endocrine cell types and immune cells in both the DSS groups treated with anti‑inflammatory agents were restored to control levels. In conclusion, our data demonstrate that there is an interaction between endocrine and immune cells during inflammation. This interaction with subsequent changes in endocrine cells is responsible for the

  8. Iron supplementation promotes gut microbiota metabolic activity but not colitis markers in human gut microbiota-associated rats.

    PubMed

    Dostal, Alexandra; Lacroix, Christophe; Pham, Van T; Zimmermann, Michael B; Del'homme, Christophe; Bernalier-Donadille, Annick; Chassard, Christophe

    2014-06-28

    The global prevalence of Fe deficiency is high and a common corrective strategy is oral Fe supplementation, which may affect the commensal gut microbiota and gastrointestinal health. The aim of the present study was to investigate the impact of different dietary Fe concentrations on the gut microbiota and gut health of rats inoculated with human faecal microbiota. Rats (8 weeks old, n 40) were divided into five (n 8 each) groups and fed diets differing only in Fe concentration during an Fe-depletion period (12 weeks) and an Fe-repletion period (4 weeks) as follows: (1) Fe-sufficient diet throughout the study period; (2) Fe-sufficient diet followed by 70 mg Fe/kg diet; (3) Fe-depleted diet throughout the study period; (4) Fe-depleted diet followed by 35 mg Fe/kg diet; (5) Fe-depleted diet followed by 70 mg Fe/kg diet. Faecal and caecal samples were analysed for gut microbiota composition (quantitative PCR and pyrosequencing) and bacterial metabolites (HPLC), and intestinal tissue samples were investigated histologically. Fe depletion did not significantly alter dominant populations of the gut microbiota and did not induce Fe-deficiency anaemia in the studied rats. Provision of the 35 mg Fe/kg diet after feeding an Fe-deficient diet significantly increased the abundance of dominant bacterial groups such as Bacteroides spp. and Clostridium cluster IV members compared with that of an Fe-deficient diet. Fe supplementation increased gut microbial butyrate concentration 6-fold compared with Fe depletion and did not affect histological colitis scores. The present results suggest that Fe supplementation enhances the concentration of beneficial gut microbiota metabolites and thus may contribute to gut health.

  9. Ulcerative colitis - discharge

    MedlinePlus

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

  10. Anti-inflammatory Mechanisms of Enteric Heligmosomoides polygyrus Infection on TNBS-Induced Colitis in a Murine Model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To model the protective mechanism of helminth infection on colitis-induced changes in immune and epithelial cell function, BALB/c mice received intra-rectal saline or TNBS (2 mg/mouse; 40% ETOH) and were studied 4 days (d) later. Separate groups of mice received oral Heligmosomoides polygyrus follow...

  11. Dietary Supplementation with a Low Dose of Polyphenol-Rich Grape Pomace Extract Prevents Dextran Sulfate Sodium-Induced Colitis in Rats.

    PubMed

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

    2016-08-01

    Evidence from several epidemiological and experimental studies points to a beneficial role of dietary polyphenols in inflammatory bowel disease. In this study, we investigate the protective effect of dietary supplementation with various amounts of a polyphenol-rich grape pomace extract (GPE) on the development of dextran sulfate sodium (DSS)-induced colitis in rats. Rats were fed 21 days on a semisynthetic diet enriched with GPE (0.1%, 0.5%, and 1%), and acute colitis was induced by DSS (40 g/L in the drinking water) administration during the last 7 days. The low GPE content in the diet (0.1%) attenuated clinical signs and colon shortening and limited DSS-induced histological lesions. GPE 0.1% also attenuated the DSS-induced increase in myeloperoxidase activity and improved superoxide dismutase activity. Higher amounts of GPE in the diet induced only weak and nonsignificant protective effects. These results suggest that consumption of a low amount of polyphenol-rich GPE helps protect against colitis development. PMID:27355494

  12. Dietary Supplementation with a Low Dose of Polyphenol-Rich Grape Pomace Extract Prevents Dextran Sulfate Sodium-Induced Colitis in Rats.

    PubMed

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

    2016-08-01

    Evidence from several epidemiological and experimental studies points to a beneficial role of dietary polyphenols in inflammatory bowel disease. In this study, we investigate the protective effect of dietary supplementation with various amounts of a polyphenol-rich grape pomace extract (GPE) on the development of dextran sulfate sodium (DSS)-induced colitis in rats. Rats were fed 21 days on a semisynthetic diet enriched with GPE (0.1%, 0.5%, and 1%), and acute colitis was induced by DSS (40 g/L in the drinking water) administration during the last 7 days. The low GPE content in the diet (0.1%) attenuated clinical signs and colon shortening and limited DSS-induced histological lesions. GPE 0.1% also attenuated the DSS-induced increase in myeloperoxidase activity and improved superoxide dismutase activity. Higher amounts of GPE in the diet induced only weak and nonsignificant protective effects. These results suggest that consumption of a low amount of polyphenol-rich GPE helps protect against colitis development.

  13. Citrobacter rodentium-induced colitis: A robust model to study mucosal immune responses in the gut.

    PubMed

    Koroleva, Ekaterina P; Halperin, Sydney; Gubernatorova, Ekaterina O; Macho-Fernandez, Elise; Spencer, Cody M; Tumanov, Alexei V

    2015-06-01

    Citrobacter rodentium is a natural mouse pathogen which reproducibly infects mice and causes intestinal disease. The C. rodentium model of infection is very useful for investigating host-pathogen immune interactions in the gut, and can also be used to understand the pathogenesis of several important human intestinal disorders, including Crohn's disease, ulcerative colitis, dysbiosis and colon tumorigenesis. Both innate and adaptive immune responses play a critical role in protection against C. rodentium. Here, we summarize the role of immune components in protection against C. rodentium and describe techniques for the analysis of innate and adaptive mucosal immune responses, including setting up the infection, analysis of colonic hyperplasia and bacterial dissemination, evaluation of antibody responses, and purification and analysis of intestinal epithelial and lymphoid cells.

  14. Ulcerative Colitis

    MedlinePlus

    Ulcerative colitis (UC) is a disease that causes inflammation and sores, called ulcers, in the lining of the rectum and colon. ... a group of diseases called inflammatory bowel disease. UC can happen at any age, but it usually ...

  15. Ulcerative colitis

    MedlinePlus

    ... is not clear if immune problems cause this illness. Stress and certain foods can trigger symptoms, but they ... Social support can often help with the stress of dealing with illness, and ... and coping with the condition. The Crohn's and Colitis ...

  16. Targeted delivery of the hydroxylase inhibitor DMOG provides enhanced efficacy with reduced systemic exposure in a murine model of colitis.

    PubMed

    Tambuwala, Murtaza M; Manresa, Mario C; Cummins, Eoin P; Aversa, Vincenzo; Coulter, Ivan S; Taylor, Cormac T

    2015-11-10

    Targeting hypoxia-sensitive pathways has recently been proposed as a new therapeutic approach to the treatment of intestinal inflammation. HIF-hydroxylases are enzymes which confer hypoxic-sensitivity upon the hypoxia-inducible factor (HIF), a major regulator of the adaptive response to hypoxia. Previous studies have shown that systemic (intraperitoneal) administration of hydroxylase inhibitors such as dimethyloxalylglycine (DMOG) is profoundly protective in multiple models of colitis, however the therapeutic potential of this approach is limited due to potential side-effects associated with systemic drug exposure and the fact that orally delivered DMOG is ineffective (likely due to drug inactivation by gastric acid). In order to overcome these issues, we formulated DMOG in a liquid emulsion drug delivery system which, when coated with specific polymer coatings, permits oral delivery of a reduced dose which is released locally throughout the colon. This colon-targeted DMOG formulation demonstrated increased relative colonic bioactivity with reduced systemic exposure and provided a similar degree of protection to systemic (intraperitoneal) administration at a 40-fold lower dose in DSS-induced colitis. In summary, targeted delivery of DMOG to the colon provides local protection resulting in enhanced efficacy with reduced systemic exposure in the treatment of colitis. This novel approach to targeting hydroxylase inhibitors to specific diseased regions of the GI tract may improve it's potential as a new therapeutic in inflammatory bowel diseases such as ulcerative colitis.

  17. Effects of AP-1 and NF-κB inhibitors on colonic endocrine cells in rats with TNBS-induced colitis

    PubMed Central

    El-Salhy, Magdy; Umezawa, Kazuo

    2016-01-01

    Interactions between intestinal neuroendocrine peptides/amines and the immune system appear to have an important role in the pathophysiology of inflammatory bowel disease (IBD). The present study investigated the effects of activator protein (AP)-1 and nuclear factor (NF)-κB inhibitors on inflammation-induced alterations in enteroendocrine cells. A total of 48 male Wistar rats were divided into the following four groups (n=12 rats/group): Control, trinitrobenzene sulfonic acid (TNBS)-induced colitis only (TNBS group), TNBS-induced colitis with 3-[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G) treatment (DTCM-G group), and TNBS-induced colitis with dehydroxymethylepoxyquinomicin (DHMEQ) treatment (DHMEQ group). A total of 3 days following administration of TNBS, the rats were treated as follows: The control and TNBS groups received 0.5 ml vehicle (0.5% carboxymethyl cellulose; CMC), respectively; the DTCM-G group received DTCM-G (20 mg/kg body weight) in 0.5% CMC; and the DHMEQ group received DHMEQ (15 mg/kg body weight) in 0.5% CMC. All injections were performed intraperitoneally twice daily for 5 days. The rats were sacrificed, and tissue samples obtained from the colon were examined histopathologically and immunohistochemically. Inflammation was evaluated using a scoring system. In addition, the sections were immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), oxyntomodulin, pancreatic polypeptide (PP) and somatostatin, and immunostaining was quantified using image-analysis software. The density of cells expressing CgA, PYY and PP was significantly lower in the TNBS group compared with in the control group, whereas the density of cells expressing serotonin, oxyntomodulin and somatostatin was significantly higher in the TNBS group compared with in the control group. None of the endocrine cell types differed significantly between the control group and either the DTCM-G or DHMEQ groups. All of the colonic endocrine cell types were affected in

  18. Effects of AP‑1 and NF‑κB inhibitors on colonic endocrine cells in rats with TNBS‑induced colitis.

    PubMed

    El-Salhy, Magdy; Umezawa, Kazuo

    2016-08-01

    Interactions between intestinal neuroendocrine peptides/amines and the immune system appear to have an important role in the pathophysiology of inflammatory bowel disease (IBD). The present study investigated the effects of activator protein (AP)‑1 and nuclear factor (NF)‑κB inhibitors on inflammation‑induced alterations in enteroendocrine cells. A total of 48 male Wistar rats were divided into the following four groups (n=12 rats/group): Control, trinitrobenzene sulfonic acid (TNBS)‑induced colitis only (TNBS group), TNBS‑induced colitis with 3‑[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM‑G) treatment (DTCM‑G group), and TNBS‑induced colitis with dehydroxymethylepoxyquinomicin (DHMEQ) treatment (DHMEQ group). A total of 3 days following administration of TNBS, the rats were treated as follows: The control and TNBS groups received 0.5 ml vehicle (0.5% carboxymethyl cellulose; CMC), respectively; the DTCM‑G group received DTCM‑G (20 mg/kg body weight) in 0.5% CMC; and the DHMEQ group received DHMEQ (15 mg/kg body weight) in 0.5% CMC. All injections were performed intraperitoneally twice daily for 5 days. The rats were sacrificed, and tissue samples obtained from the colon were examined histopathologically and immunohistochemically. Inflammation was evaluated using a scoring system. In addition, the sections were immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), oxyntomodulin, pancreatic polypeptide (PP) and somatostatin, and immunostaining was quantified using image‑analysis software. The density of cells expressing CgA, PYY and PP was significantly lower in the TNBS group compared with in the control group, whereas the density of cells expressing serotonin, oxyntomodulin and somatostatin was significantly higher in the TNBS group compared with in the control group. None of the endocrine cell types differed significantly between the control group and either the DTCM‑G or DHMEQ groups. All of the colonic

  19. Pseudomembranous Colitis

    PubMed Central

    Farooq, Priya D.; Urrunaga, Nathalie H.; Tang, Derek M.; von Rosenvinge, Erik C.

    2015-01-01

    Pseudomembranous colitis is an inflammatory condition of the colon characterized by elevated yellow-white plaques that coalesce to form pseudomembranes on the mucosa. Patients with the condition commonly present with abdominal pain, diarrhea, fever, and leukocytosis. Because pseudomembranous colitis is often associated with C. difficile infection, stool testing and empiric antibiotic treatment should be initiated when suspected. When results of C. difficile testing are negative and symptoms persist despite escalating empiric treatment, early gastroenterology consultation and lower endoscopy would be the next step in the appropriate clinical setting. If pseudomembranous colitis is confirmed endoscopically, colonic biopsies should be obtained, as histology can offer helpful clues to the underlying diagnosis. The less common non-C. difficile causes of pseudomembranous colitis should be entertained, as a number of etiologies can result in this condition. Examples include Behcet’s disease, collagenous colitis, inflammatory bowel disease, ischemic colitis, other infections organisms (e.g. bacteria, parasites, viruses), and a handful of drugs and toxins. Pinpointing the correct underlying etiology would better direct patient care and disease management. Surgical specialists would be most helpful in colonic perforation, gangrenous colon, or severe disease. PMID:25769243

  20. Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells.

    PubMed

    Rossini, Valerio; Radulovic, Katarina; Riedel, Christian U; Niess, Jan Hendrik

    2016-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammation which affects the gastrointestinal tract (GIT). One of the best ways to study the immunological mechanisms involved during the disease is the T cell transfer model of colitis. In this model, immunodeficient mice (RAG(-/-) recipients) are reconstituted with naive CD4(+) T cells from healthy wild type hosts. This model allows examination of the earliest immunological events leading to disease and chronic inflammation, when the gut inflammation perpetuates but does not depend on a defined antigen. To study the potential role of antigen presenting cells (APCs) in the disease process, it is helpful to have an antigen-driven disease model, in which a defined commensal-derived antigen leads to colitis. An antigen driven-colitis model has hence been developed. In this model OT-II CD4(+) T cells, that can recognize only specific epitopes in the OVA protein, are transferred into RAG(-/-) hosts challenged with CFP-OVA-expressing E. coli. This model allows the examination of interactions between APCs and T cells in the lamina propria. PMID:27684040

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

    PubMed

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

    2016-03-01

    Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions of the gut that include ulcerative colitis and Crohn's disease. Probiotics are live micro-organisms that may be used as adjuvant therapy for patients with IBD. The aim of this study was to evaluate the effect of prophylactic ingestion of Escherichia coli strain Nissle 1917 (EcN) in a murine model of colitis. For induction of colitis, mice were given a 3.5% dextran sodium sulfate (DSS) solution for 7 days in drinking water. EcN administration to mice subjected to DSS-induced colitis resulted in significant reduction in clinical and histopathological signs of disease and preservation of intestinal permeability. We observed reduced inflammation, as assessed by reduced levels of neutrophils, eosinophils, chemokines and cytokines. We observed an increase in the number of regulatory T-cells in Peyer's patches. Germ-free mice received faecal content from control or EcN-treated mice and were then subjected to DSS-induced colitis. We observed protection from colitis in animals that were colonized with faecal content from EcN-treated mice. These results suggest that preventative oral administration of EcN or faecal microbiota transplantation with EcN-containing microbiota ameliorates DSS-induced colitis by modifying inflammatory responsiveness to DSS. PMID:26758971

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

    PubMed

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

    2016-03-01

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

  3. Investigation of Host and Pathogen Contributions to Infectious Colitis Using the Citrobacter rodentium Mouse Model of Infection.

    PubMed

    Bosman, Else S; Chan, Justin M; Bhullar, Kirandeep; Vallance, Bruce A

    2016-01-01

    Citrobacter rodentium is used as a model organism to study enteric bacterial infections in mice. Infection occurs via the oral-fecal route and results in the pathogen forming attaching and effacing lesions on infected epithelial cells. Moreover, infection leads to a subsequent host-mediated form of colitis. C. rodentium infection is thus an excellent model to study infectious colitis in vivo, while the ability to genetically manipulate C. rodentium virulence genes provides the opportunity to develop clear insights into the pathogenesis of this and related infectious microbes. This chapter outlines the basic techniques involved in setting up a C. rodentium infection in mice and several different methodologies to assess the severity of the infection.

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

    PubMed

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

    2015-10-15

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

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

    PubMed

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

    2015-10-01

    In this study, we evaluated the effects of dietary plant sterols and stanols as their fatty acid esters on the development of experimental colitis. The effects were studied both in high- and low-fat diet conditions in two models, one acute and another chronic model of experimental colitis that resembles gene expression in human inflammatory bowel disease (IBD). In the first experiments in the high fat diet (HFD), we did not observe a beneficial effect of the addition of plant sterols and stanols on the development of acute dextran sulphate sodium (DSS) colitis. In the chronic CD4CD45RB T cell transfer colitis model, we mainly observed an effect of the presence of high fat on the development of colitis. In this HFD condition, the presence of plant sterol or stanol did not result in any additional effect. In the second experiments with low fat, we could clearly observe a beneficial effect of the addition of plant sterols on colitis parameters in the T cell transfer model, but not in the DSS model. This positive effect was related to the gender of the mice and on Treg presence in the colon. This suggests that especially dietary plant sterol esters may improve intestinal inflammation in a T cell dependent manner. PMID:26501315

  6. [Ulcerative colitis].

    PubMed

    Lopetuso, Loris; Gasbarrini, Antonio

    2016-06-01

    Inflammatory bowel disease (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing inflammatory disorders of the digestive tract resulting from dysregulated immune responses toward environmental factors in genetically predisposed individuals. This review focus on what is the state of the art of UC pathophysiology, diagnosis, and treatment and how any future findings could drive our clinical practice. PMID:27362722

  7. Comparison of anti-inflammatory mechanisms of mango (Mangifera Indica L.) and pomegranate (Punica Granatum L.) in a preclinical model of colitis

    PubMed Central

    Kim, Hyemee; Banerjee, Nivedita; Ivanov, Ivan; Pfent, Catherine M.; Prudhomme, Kalan R.; Bisson, William H.; Dashwood, Rodrick H.; Talcott, Stephen T.; Mertens-Talcott, Susanne U.

    2016-01-01

    Scope Tannin-rich fruits have been evaluated as alternative prevention strategies for colorectal cancer based on their anti-inflammatory properties. This study compared tannin-rich preparations from mango (rich in gallotannins) and pomegranate (rich in ellagitannins) in the dextran sodium sulfate-induced colitis model. Methods and results In rats, mango and pomegranate beverages decreased intestinal inflammation and the levels of pro-inflammatory cytokines in mucosa and serum. The mango beverage suppressed the ratio of phosphorylated/total protein expression of the IGF-1R-AKT/mTOR axis and down-regulated mRNA expression of Igf1, Insr, and pik3cv. Pomegranate decreased p70S6K and RPS6, as well as Rps6ka2, Map2k2, and Mapk1 mRNA. In silico modeling indicated a high binding-docked of gallic acid to the catalytic domain of IGF-1R, which may suppress the activity of the enzyme. Ellagic acid docked effectively into the catalytic domains of both IGF-1R and EGFR. In vitro assays with lipopolysaccharide-treated CCD-18Co cells using polyphenolic extracts from each beverage, as well as pure compounds, corroborated the predictions made in silico. Conclusion Mango polyphenols inhibited the IGF-1R- AKT/mTOR axis, and pomegranate polyphenols downregulate the mTOR downstream pathway through reductions in ERK1/2. These results suggest that extracts rich in gallo- and ellagitannins act on different molecular targets in the protection against ulcerative colitis. PMID:27028006

  8. Food-grade titanium dioxide exposure exacerbates tumor formation in colitis associated cancer model.

    PubMed

    Urrutia-Ortega, Ismael M; Garduño-Balderas, Luis G; Delgado-Buenrostro, Norma L; Freyre-Fonseca, Verónica; Flores-Flores, José O; González-Robles, Arturo; Pedraza-Chaverri, José; Hernández-Pando, Rogelio; Rodríguez-Sosa, Miriam; León-Cabrera, Sonia; Terrazas, Luis I; van Loveren, Henk; Chirino, Yolanda I

    2016-07-01

    Colorectal cancer is the fourth worldwide cause of death and even if some dietary habits are consider risk factors, the contribution of food additives including foodgrade titanium dioxide (TiO2), designated as E171, has been poorly investigated. We hypothesized that oral E171 intake could have impact on the enhancement of colorectal tumor formation and we aimed to investigate if E171 administration could enhance tumor formation in a colitis associated cancer (CAC) model. BALB/c male mice were grouped as follows: a) control, b) E171, c) CAC and d) CAC + E171 group (n = 6). E171 used in this study formed agglomerates of 300 nm in water. E171 intragastric administration (5 mg/kg body weight/5 days/10 weeks) was unable to induce tumor formation but dysplastic alterations were observed in the distal colon but enhanced the tumor formation in distal colon (CAC + E171 group) measured by tumor progression markers. Some E171 particles were internalized in colonic cells of the E171 and CAC + E171 groups and both groups showed a decrease in goblet cells in the distal colon. However the CAC + E171 group showed a higher decrease of these cells that act as protection barrier in colon. These results suggest that E171 could worsen pre-existent intestinal diseases.

  9. Profiles of microRNA networks in intestinal epithelial cells in a mouse model of colitis.

    PubMed

    Lee, Juneyoung; Park, Eun Jeong; Yuki, Yoshikazu; Ahmad, Shandar; Mizuguchi, Kenji; Ishii, Ken J; Shimaoka, Motomu; Kiyono, Hiroshi

    2015-12-09

    Inflammatory bowel diseases (IBDs) accompany a critical loss of the frontline barrier function that is achieved primarily by intestinal epithelial cells (IECs). Although the gene-regulation pathways underlying these host-defense roles of IECs presumably are deranged during IBD pathogenesis, the quantitative and qualitative alterations of posttranscriptional regulators such as microRNAs (miRNAs) within the cells largely remain to be defined. We aimed to uncover the regulatory miRNA-target gene relationships that arise differentially in inflamed small- compared with large-IECs. Whereas IBD significantly increased the expression of only a few miRNA candidates in small-IECs, numerous miRNAs were upregulated in inflamed large-IECs. These marked alterations might explain why the large, as compared with small, intestine is more sensitive to colitis and shows more severe pathology in this experimental model of IBD. Our in-depth assessment of the miRNA-mRNA expression profiles and the resulting networks prompts us to suggest that miRNAs such as miR-1224, miR-3473a, and miR-5128 represent biomarkers that appear in large-IECs upon IBD development and co-operatively repress the expression of key anti-inflammatory factors. The current study provides insight into gene-regulatory networks in IECs through which dynamic rearrangement of the involved miRNAs modulates the gene expression-regulation machinery between maintaining and disrupting gastrointestinal homeostasis.

  10. CMV - gastroenteritis/colitis

    MedlinePlus

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

  11. Retrotransposition of long interspersed nucleotide element-1 is associated with colitis but not tumors in a murine colitic cancer model.

    PubMed

    Otsubo, Takeshi; Okamura, Tadashi; Hagiwara, Teruki; Ishizaka, Yukihito; Dohi, Taeko; Kawamura, Yuki I

    2015-01-01

    Long interspersed element-1 (L1) is a transposable element that can move within the genome, potentially leading to genome diversity and modified gene function. Although L1 activity in somatic cells is normally suppressed through DNA methylation, some L1s are activated in tumors including colorectal carcinoma. However, how L1-retrotransposition (L1-RTP) is involved in gastrointestinal disorders remains to be elucidated. We hypothesized that L1-RTP in somatic cells might contribute to colitis-associated cancer (CAC). To address this, we employed an experimental model of CAC using transgenic L1-reporter mice carrying a human L1-EGFP reporter gene. Mice were subjected to repeated cycles of colitis induced by administration of dextran sodium sulfate (DSS) in drinking water with injection of carcinogen azoxymethane (AOM). L1-RTP levels were measured by a quantitative polymerase chain reaction targeting the newly inserted reporter EGFP in various tissues and cell types, including samples obtained by laser microdissection and cell sorting with flow cytometry. DNA methylation levels of the human L1 promoter were analyzed by bisulfite pyrosequencing. AOM+DSS-treated mice exhibited significantly higher levels of L1-RTP in whole colon tissue during the acute phase of colitis when compared with control naïve mice. L1-RTP levels in whole colon tissue were positively correlated with the histological severity of colitis and degree of neutrophil infiltration into the lamina propria (LP), but not with tumor development in the colon. L1-RTP was enriched in LP mesenchymal cells rather than epithelial cells (ECs), myeloid, or lymphoid cells. DNA methylation levels of the human L1 promoter region showed a negative correlation with L1-RTP levels. L1-RTP was absent from most tumors found in 22-week-old mice. In conclusion, we demonstrated that L1-RTP was induced in the mouse CAC mucosa in accordance with the acute inflammatory response; however, retrotransposition appears not to have

  12. Ischemic Colitis

    PubMed Central

    FitzGerald, James F.; Hernandez III, Luis O.

    2015-01-01

    Most clinicians associate ischemic colitis with elderly patients who have underlying cardiovascular comorbidities. While the majority of cases probably occur in this population, the disease can present in younger patients as a result of different risk factors, making the diagnosis challenging. While a majority of patients respond to medical management, surgery is required in approximately 20% of the cases and is associated with high morbidity and mortality. PMID:26034405

  13. Panax notoginseng attenuates experimental colitis in AOM/DSS mouse model

    PubMed Central

    Wen, Xiao-Dong; Wang, Chong-Zhi; Yu, Chunhao; Zhao, Lei; Zhang, Zhiyu; Matin, Adiba; Wang, Yunwei; Li, Ping; Xiao, Shu-Yuan; Du, Wei; He, Tong-Chuan; Yuan, Chun-Su

    2013-01-01

    Patients suffering from inflammatory bowel disease are at a high risk of developing colorectal cancer. To assess the anti-cancer potential of botanicals, in this study, we evaluated the effects of Panax notoginseng on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis. One week after A/J mice received AOM, the animals received DSS for 8 days, or were supplemented with P. notoginseng extract, at 30 or 90 mg/kg. DSS-induced colitis was scored with the disease activity index (DAI). The severity of the inflammatory lesions was evaluated by a colon tissue histological assessment. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were also explored. We observed that the effects of P. notoginseng on the reduction of colon inflammation, expressed in DAI score, were in a dose-related manner (P < 0.01). P. notoginseng inhibited the reduction of the colon length and the loss of bodyweight in dose-related manner (all P < 0.05). The histological assessment of the colitis and inflammatory related immunohistochemical data also supported the pharmacological observations. Our data suggest that P. notoginseng is a promising candidate in preventing and treating colitis and inflammation-associated colon carcinogenesis. PMID:24142591

  14. Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model

    PubMed Central

    Huo, Xiaowei; Liu, Dongyu; Gao, Li; Li, Liyong; Cao, Li

    2016-01-01

    Inflammatory bowel disease (IBD) is generally considered as a major risk factor in the progression of colitis-associated carcinogenesis (CAC). Thus, it is well accepted that ameliorating inflammation creates a potential to achieve an inhibitory effect on CAC. Licorice flavonoids (LFs) possess strong anti-inflammatory activity, making it possible to investigate its pharmacologic role in suppressing CAC. The purpose of the present study was to evaluate the anti-tumor potential of LFs, and further explore the underlying mechanisms. Firstly, an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model was established and administered with or without LFs for 10 weeks, and then the severity of CAC was examined macroscopically and histologically. Subsequently, the effects of LFs on expression of proteins associated with apoptosis and proliferation, levels of inflammatory cytokine, expression of phosphorylated-Janus kinases 2 (p-Jak2) and phosphorylated-signal transducer and activator of transcription 3 (p-Stat3), and activation of nuclear factor-κB (NFκB) and P53 were assessed. We found that LFs could significantly reduce tumorigenesis induced by AOM/DSS. Further study revealed that LFs treatment substantially reduced activation of NFκB and P53, and subsequently suppressed production of inflammatory cytokines and phosphorylation of Jak2 and Stat3 in AOM/DSS-induced mice. Taken together, LFs treatment alleviated AOM/DSS induced CAC via P53 and NFκB/IL-6/Jak2/Stat3 pathways, highlighting the potential of LFs in preventing CAC. PMID:27563884

  15. Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model.

    PubMed

    Huo, Xiaowei; Liu, Dongyu; Gao, Li; Li, Liyong; Cao, Li

    2016-08-24

    Inflammatory bowel disease (IBD) is generally considered as a major risk factor in the progression of colitis-associated carcinogenesis (CAC). Thus, it is well accepted that ameliorating inflammation creates a potential to achieve an inhibitory effect on CAC. Licorice flavonoids (LFs) possess strong anti-inflammatory activity, making it possible to investigate its pharmacologic role in suppressing CAC. The purpose of the present study was to evaluate the anti-tumor potential of LFs, and further explore the underlying mechanisms. Firstly, an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model was established and administered with or without LFs for 10 weeks, and then the severity of CAC was examined macroscopically and histologically. Subsequently, the effects of LFs on expression of proteins associated with apoptosis and proliferation, levels of inflammatory cytokine, expression of phosphorylated-Janus kinases 2 (p-Jak2) and phosphorylated-signal transducer and activator of transcription 3 (p-Stat3), and activation of nuclear factor-κB (NFκB) and P53 were assessed. We found that LFs could significantly reduce tumorigenesis induced by AOM/DSS. Further study revealed that LFs treatment substantially reduced activation of NFκB and P53, and subsequently suppressed production of inflammatory cytokines and phosphorylation of Jak2 and Stat3 in AOM/DSS-induced mice. Taken together, LFs treatment alleviated AOM/DSS induced CAC via P53 and NFκB/IL-6/Jak2/Stat3 pathways, highlighting the potential of LFs in preventing CAC.

  16. Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model.

    PubMed

    Huo, Xiaowei; Liu, Dongyu; Gao, Li; Li, Liyong; Cao, Li

    2016-01-01

    Inflammatory bowel disease (IBD) is generally considered as a major risk factor in the progression of colitis-associated carcinogenesis (CAC). Thus, it is well accepted that ameliorating inflammation creates a potential to achieve an inhibitory effect on CAC. Licorice flavonoids (LFs) possess strong anti-inflammatory activity, making it possible to investigate its pharmacologic role in suppressing CAC. The purpose of the present study was to evaluate the anti-tumor potential of LFs, and further explore the underlying mechanisms. Firstly, an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model was established and administered with or without LFs for 10 weeks, and then the severity of CAC was examined macroscopically and histologically. Subsequently, the effects of LFs on expression of proteins associated with apoptosis and proliferation, levels of inflammatory cytokine, expression of phosphorylated-Janus kinases 2 (p-Jak2) and phosphorylated-signal transducer and activator of transcription 3 (p-Stat3), and activation of nuclear factor-κB (NFκB) and P53 were assessed. We found that LFs could significantly reduce tumorigenesis induced by AOM/DSS. Further study revealed that LFs treatment substantially reduced activation of NFκB and P53, and subsequently suppressed production of inflammatory cytokines and phosphorylation of Jak2 and Stat3 in AOM/DSS-induced mice. Taken together, LFs treatment alleviated AOM/DSS induced CAC via P53 and NFκB/IL-6/Jak2/Stat3 pathways, highlighting the potential of LFs in preventing CAC. PMID:27563884

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

    PubMed Central

    Castro-Mejía, Josué; Jakesevic, Maja; Krych, Łukasz; Nielsen, Dennis S.; Hansen, Lars H.; Sondergaard, Bodil C.; Kvist, Peter H.; Hansen, Axel K.; Holm, Thomas L.

    2016-01-01

    Background and Aim. Crohn's disease is associated with gut microbiota (GM) dysbiosis. Treatment with the anti-IL-12p40 monoclonal antibody (12p40-mAb) has therapeutic effect in Crohn's disease patients. This study addresses whether a 12p40-mAb treatment influences gut microbiota (GM) composition in mice with adoptive transfer colitis (AdTr-colitis). Methods. AdTr-colitis mice were treated with 12p40-mAb or rat-IgG2a or NaCl from days 21 to 47. Disease was monitored by changes in body weight, stool, endoscopic and histopathology scores, immunohistochemistry, and colonic cytokine/chemokine profiles. GM was characterized through DGGE and 16S rRNA gene-amplicon high-throughput sequencing. Results. Following 12p40-mAb treatment, most clinical and pathological parameters associated with colitis were either reduced or absent. GM was shifted towards a higher Firmicutes-to-Bacteroidetes ratio compared to rat-IgG2a treated mice. Significant correlations between 17 bacterial genera and biological markers were found. The relative abundances of the RF32 order (Alphaproteobacteria) and Akkermansia muciniphila were positively correlated with damaged histopathology and colonic inflammation. Conclusions. Shifts in GM distribution were observed with clinical response to 12p40-mAb treatment, whereas specific GM members correlated with colitis symptoms. Our study implicates that specific changes in GM may be connected with positive clinical outcomes and suggests preventing or correcting GM dysbiosis as a treatment goal in inflammatory bowel disease. PMID:26880890

  18. Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity.

    PubMed Central

    Rachmilewitz, D; Karmeli, F; Okon, E; Bursztyn, M

    1995-01-01

    Enhanced nitric oxide (NO) generation by stimulated NO synthase (NOS) activity may, through its oxidative metabolism contribute to tissue injury in experimental colitis. In this study the possible amelioration of experimental colitis by NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS activity, was evaluated. Colitis was induced in rats by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB) dissolved in 0.25 ml 50% ethanol or by flushing the colon of capsaicin pretreated rats with 2 ml of 5% acetic acid. In several experiments, L-NAME 0.1 mg/ml was added to the drinking water at the time of colitis induction with TNB or seven days before acetic acid treatment. Rats were killed at various time intervals after induction of colitis. A 10 cm distal colonic segment was isolated, weighed, lesion area measured, and explants organ cultured for 24 hours for determination of NO generation by the Greiss reaction. The rest of the mucosa was scraped for determination of myeloperoxidase and NOS activities and leukotriene generation. In TNB treated rats mean arterial pressure was also determined up to 72 hours after damage induction, with or without cotreatment with nitroprusside. L-NAME significantly decreased the extent of tissue injury in TNB treated rats. Seven days after TNB treatment lesion area was reduced by 55%, colonic weight by 37%, and myeloperoxidase and NOS activity by 59% and 42%, respectively. Acetic acid induced colitis in capsaicin pretreated rats was also significantly decreased by L-NAME. Twenty four hours after acetic acid treatment lesion area was reduced by 61%, colonic weight by 21% and NOS activity by 39%. Mean (SEM) arterial blood pressure in TNB+L-NAME treated rats was 37.6 (8.1) mm Hg higher than in TNB treated rats, an effect that was only partially abolished by nitroprusside. These results show that inhibition of NO synthesis by an L-arginine analogue significantly ameliorates the extent of tissue injury in two

  19. Colitis after Hibiclens enema.

    PubMed

    Hardin, R D; Tedesco, F J

    1986-10-01

    Acute colitis occurred after a Hibiclens cleanser enema. Endoscopic and histologic features were not helpful in distinguishing this colitis from an infectious or idiopathic colitis, and a careful history proved invaluable. We review the complications of using soapsuds and various chemical-containing enemas; these complications range from mild colitis to death. Because soap and other chemicals are damaging to colonic mucosa, these enemas should be included as a cause of acute colitis.

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

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2016-10-01

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

  2. Id1 Deficiency Protects against Tumor Formation in Apc(Min/+) Mice but Not in a Mouse Model of Colitis-Associated Colon Cancer.

    PubMed

    Zhang, Ning; Subbaramaiah, Kotha; Yantiss, Rhonda K; Zhou, Xi Kathy; Chin, Yvette; Benezra, Robert; Dannenberg, Andrew J

    2015-04-01

    Different mechanisms contribute to the development of sporadic, hereditary and colitis-associated colorectal cancer. Inhibitor of DNA binding/differentiation (Id) proteins act as dominant-negative antagonists of basic helix-loop-helix transcription factors. Id1 is a promising target for cancer therapy, but little is known about its role in the development of colon cancer. We used immunohistochemistry to demonstrate that Id1 is overexpressed in human colorectal adenomas and carcinomas, whether sporadic or syndromic. Furthermore, elevated Id1 levels were found in dysplasia and colon cancer arising in patients with inflammatory bowel disease. Because levels of PGE2 are also elevated in both colitis and colorectal neoplasia, we determined whether PGE2 could induce Id1. PGE2 via EP4 stimulated protein kinase A activity resulting in enhanced pCREB-mediated Id1 transcription in human colonocytes. To determine the role of Id1 in carcinogenesis, two mouse models were used. Consistent with the findings in humans, Id1 was overexpressed in tumors arising in both Apc(Min) (/+) mice, a model of familial adenomatous polyposis, and in experimental colitis-associated colorectal neoplasia. Id1 deficiency led to significant decrease in the number of intestinal tumors in Apc(Min) (/+) mice and prolonged survival. In contrast, Id1 deficiency did not affect the number or size of tumors in the model of colitis-associated colorectal neoplasia, likely due to exacerbation of colitis associated with Id1 loss. Collectively, these results suggest that Id1 plays a role in gastrointestinal carcinogenesis. Our findings also highlight the need for different strategies to reduce the risk of colitis-associated colorectal cancer compared with sporadic or hereditary colorectal cancer.

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

    PubMed

    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.

  4. Fucoidan Extracts Ameliorate Acute Colitis.

    PubMed

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

    2015-01-01

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

  5. Implication of TNF-alpha convertase (TACE/ADAM17) in inducible nitric oxide synthase expression and inflammation in an experimental model of colitis.

    PubMed

    Colón, A L; Menchén, L A; Hurtado, O; De Cristóbal, J; Lizasoain, I; Leza, J C; Lorenzo, P; Moro, M A

    2001-12-21

    Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine which is shed in its soluble form by a disintegrin and metalloproteinase (ADAM) called TNF-alpha convertase (TACE; ADAM17). TNF-alpha plays a role in inflammatory bowel disease (IBD) and is involved in the expression of inducible nitric oxide synthase (iNOS) which has also been implicated in IBD. The study was designed to investigate whether colitis induced by trinitrobenzene sulphonic acid (TNBS) in rats produces an increase in TACE activity and/or expression and whether its pharmacological inhibition reduces TNF-alpha levels, iNOS expression and colonic damage in this model. TNBS (30 mg in 0.4 ml of 50% ethanol) was instilled into the colon of female Wistar rats. Saline or TACE inhibitor BB1101 (10 mg/kg/day) was administered intraperitoneally 5 days after TNBS instillation. On day 10, colons were removed and assessed for pathological score, myeloperoxidase (MPO), NO synthase (NOS), TACE enzymatic activity and protein levels, colonic TNF-alpha and NOx- levels. Instillation of TNBS caused an increase in TACE activity and expression and the release of TNF-alpha. TNBS also resulted in iNOS expression and colonic damage. BB1101 blocked TNBS-induced increase in TACE activity, TNF-alpha release and iNOS expression. Concomitantly, BB1101 ameliorated TNBS-induced colonic damage and inflammation. TNBS causes TNF-alpha release by an increase in TACE activity and expression and this results in the expression of iNOS and subsequent inflammation, suggesting that TACE inhibition may prove useful as a therapeutic means in IBD. PMID:11884025

  6. Glucagon-like peptide-2-loaded microspheres as treatment for ulcerative colitis in the murine model.

    PubMed

    Wu, Jie; Qi, Keke; Xu, Ziwei; Wan, Jin

    2015-01-01

    Glucagon-like peptide-2 (GLP-2) is an intestinal hormone that promotes intestinal growth, but the rapid degradation by dipeptidyl peptidase-IV limits its applications. PLGA microsphere is a well-developed drug delivery system, while seldom been studied as a solution for prolonging in vivo effects of GLP-2. In this study, we encapsulated porcine GLP-2 (pGLP-2) into microspheres and investigated its therapeutic effects in dextran sulfate sodium (DSS)-treated mice. pGLP-2 microspheres showed 20.36% in initial burst and constant release for at least 9 d. In the DSS-treated mice, a single injection of GLP-2 microspheres significantly increased the body weight, colonic length, small intestinal weight and mRNA expression of Occludin, decreased the colonic damage score, mRNA expression of IL-6, IL-10, TNF-α and IFN-γ. In conclusion, pGLP-2 microspheres were resistant to degradation and decreased the severity of DSS-induced ulcerative colitis which suggested that GLP-2-loaded microspheres could be a proper candidate for the treatment of ulcerative colitis.

  7. Dextran sulfate sodium (DSS)-induced colitis in mice.

    PubMed

    Chassaing, Benoit; Aitken, Jesse D; Malleshappa, Madhu; Vijay-Kumar, Matam

    2014-01-01

    Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis and Crohn's Disease, are complex and multifactorial diseases with unknown etiology. For the past 20 years, to study human IBD mechanistically, a number of murine models of colitis have been developed. These models are indispensable tools to decipher underlying mechanisms of IBD pathogenesis as well as to evaluate a number of potential therapeutics. Among various chemically induced colitis models, the dextran sulfate sodium (DSS)-induced colitis model is widely used because of its simplicity and many similarities with human ulcerative colitis. This model has both advantages and disadvantages that must be considered when employed. This protocol describes the DSS-induced colitis model, focusing on details and factors that could affect DSS-induced pathology. PMID:24510619

  8. Dextran sulfate sodium (DSS)-induced colitis in mice.

    PubMed

    Chassaing, Benoit; Aitken, Jesse D; Malleshappa, Madhu; Vijay-Kumar, Matam

    2014-02-04

    Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis and Crohn's Disease, are complex and multifactorial diseases with unknown etiology. For the past 20 years, to study human IBD mechanistically, a number of murine models of colitis have been developed. These models are indispensable tools to decipher underlying mechanisms of IBD pathogenesis as well as to evaluate a number of potential therapeutics. Among various chemically induced colitis models, the dextran sulfate sodium (DSS)-induced colitis model is widely used because of its simplicity and many similarities with human ulcerative colitis. This model has both advantages and disadvantages that must be considered when employed. This protocol describes the DSS-induced colitis model, focusing on details and factors that could affect DSS-induced pathology.

  9. Is indeterminate colitis determinable?

    PubMed

    Tremaine, William J

    2012-04-01

    About 10% of patients with colitis due to inflammatory bowel disease have indeterminate colitis. Despite newer diagnostic tools, the frequency has not diminished over the past 33 years. The current preferred term among academicians is colonic inflammatory bowel disease unclassified(IBDU), although indeterminate colitis is the term endorsed for inclusion in the ICD-10 coding system. Indeterminate colitis is more frequent among children. Theanti-Saccharomyces cerevisiae (ASCA) and perinuclear anti-cytoplasmic antibody (pANCA) are useful in distinguishing IBDU from ulcerative colitis and Crohn’s disease. However, current serologic and genetic studies, as well as endoscopic and imaging studies lack sufficient positive predictive values to make a definite diagnosis of Crohn’s colitis or ulcerative colitis. Patients with IBDU who undergo proctocolectomy with ileal pouch-anal anastomosis have more complications than patients with ulcerative colitis. Although some patients with indeterminate colitis eventually develop characteristic ulcerative colitis or Crohn’s disease, a subgroup are durably indeterminate. PMID:22314810

  10. Regulation of the alternative pathway of complement modulates injury and immunity in a chronic model of dextran sulphate sodium-induced colitis

    PubMed Central

    Elvington, M; Schepp-Berglind, J; Tomlinson, S

    2015-01-01

    The role of complement in inflammatory bowel disease (IBD) has been studied primarily using acute models, and it is unclear how complement affects processes in more relevant chronic models of IBD in which modulation of adaptive immunity and development of fibrosis have pathogenic roles. Using mice deficient in C1q/mannose-binding lectin (MBL) or C3, we demonstrated an important role for these opsonins and/or the classical pathway C3 convertase in providing protection against mucosal injury and infection in a model of chronic dextran sulphate sodium (DSS)-induced colitis. In contrast, deficiency of the alternative pathway (fB–/– mice) had significantly less impact on injury profiles. Consequently, the effect of a targeted inhibitor of the alternative pathway was investigated in a therapeutic protocol. Following the establishment of colitis, mice were treated with CR2-fH during subsequent periods of DSS treatment and acute injury (modelling relapse). CR2-fH significantly reduced complement activation, inflammation and injury in the colon, and additionally reduced fibrosis. Alternative pathway inhibition also altered the immune response in the chronic state in terms of reducing numbers of B cells, macrophages and mature dendritic cells in the lamina propria. This study indicates an important role for the alternative pathway of complement in the pathogenesis and the shaping of an immune response in chronic DSS-induced colitis, and supports further investigation into the use of targeted alternative pathway inhibition for the treatment of IBD. PMID:25293413

  11. Crohn's & Colitis Foundation of America

    MedlinePlus

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

  12. Protective effects of Semen Crotonis Pulveratum on trinitrobenzene sulphonic acid-induced colitis in rats and H₂O₂-induced intestinal cell apoptosis in vitro.

    PubMed

    Wang, Xiaohong; Zhao, Jie; Han, Zhe; Tang, Fang

    2015-06-01

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Semen Crotonis Pulveratum (SCP) has been used as a traditional medicine for the treatment of UC. However, its molecular mechanisms of action have not yet been elucidated. In the present study, we aimed to investigate the preliminary mechanisms of the role of SCP on trinitrobenzene sulphonic acid (TNBS)-induced UC in rats and hydrogen peroxide (H2O2)-induced intestinal cell apoptosis in vitro. Wistar rats (n=9 per group) were randomly divided into 4 groups: the normal control group, the UC group, the UC + SCP group and the UC + sulfasalazine group as a positive control. The proportion of CD4+CD25+ T cells and CD4+CD25+Foxp3+ Tregs, and the expression levels of interleukin (IL)-6 and IL-10 in the peripheral blood, as well as the expression levels of cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1) in the colon tissues were determined by flow cytometry, ELISA and immunohistochemical staining, respectively. Rat intestinal epithelial (IEC-6) cell apoptosis induced by H2O2 was determined by TUNEL assay, flow cytometry using Annexin V/propidium iodide (PI) staining and western blot analysis of caspase-3 activation, respectively. Significantly higher proportions of circulating CD4+CD25+ T cells and CD4+CD25+Foxp3+ Tregs were present in the UC + SCP group compared with the UC group. A significantly decreased expression of IL-6 and an increased expression of IL-10 were also observed in the UC + SCP group compared with UC group. SCP significantly reduced the UC-induced increase in the expression of COX-2 and ICAM-1 in the colon tissues. SCP inhibited cell apoptosis and caspase-3 activation induced by H2O2 in the ICE-6 cells. Our data thus indicate that SCP inhibits inflammation in UC by increasing the proportion of circulating Tregs, altering cytokine production and decreasing COX-2 and ICAM-1 expression. In addition it protects against H2O2-induced intestinal cell apoptosis in vitro.

  13. Effects of Glutamine and Omega-3 Fatty Acids on Erythrocyte Deformability and Oxidative Damage in Rat Model of Enterocolitis

    PubMed Central

    Cehreli, Ruksan; Akpinar, Hale; Artmann, Aysegul Temiz; Sagol, Ozgul

    2015-01-01

    Background The aim of the study was to investigate preventive effects of glutamine (Gln), omega-3 fatty acids (FA) on erythrocyte deformability (EDEF) in rat model of indomethacin-induced enterocolitis. Methods Nineteen Wistar albino male rats were divided into three groups: control group, colitis induced by indomethacin and were fed with a standard laboratory diet (group 1), and colitis induced by indomethacin and were also fed with Gln, omega-3 FA (group 2). An investigation was performed in a rat model of experimental colitis induced by subcutaneous injections of 2 mL intdomethacine solution applied at 24 and 48 hours intervals to male Wistar rats for 14 days. Gln and omega-3 FA were added to the daily standard diets of the animals during 14 days of injections. During the study, changes in body weight were evaluated. The intestines were examined, and colitis was macroscopic and histologically scored. The circulating tumor necrosis factor alpha (TNF-α) and interleukine-1β (IL-1β), erythrocyte transit time (ETT) and thiobarbituric acid reactive substances (TBARS) levels were determined in addition to calculation of EDEF indices in all groups. Results No significant differences in body weight changes could be determined between the standard diet and special diet groups at the end of the experiment. After macroscopic and microscopic scoring, in all of the groups that colitis was found induced, the lowest microscopic score was observed in the group 2. But Gln and omega-3 FA supplemented diet did not change the mean macroscopic and histological scores in all rats. The proliferating cell nuclear antigen (PCNA) levels were significantly higher in group 1 and group 2 compared to the control group. Effects of the diet on circulating TNF-α and IL-1β levels were found correlated with inflammation but statistically significant differences were not found in the group 1 and group 2 (P < 0.05). The ETT and TBARS levels in standard and special diet groups were significantly

  14. Embelin lipid nanospheres for enhanced treatment of ulcerative colitis - Preparation, characterization and in vivo evaluation.

    PubMed

    Badamaranahalli, Shivaram Shivakumar; Kopparam, Manjunath; Bhagawati, Siddalingappa Tippanna; Durg, Sharanbasappa

    2015-08-30

    Aim of the present study is to develop embelin lipid nanospheres (LNE) for better treatment of ulcerative colitis. Embelin LNs were developed using soya bean oil/virgin coconut oil as liquid lipid carrier and soya/egg lecithin as stabilizer by hot homogenization followed by ultrasonication technique. The particle size of LNEs ranged from 196.1±3.57 to 269.2±1.05nm with narrow polydispersity index values whereas zeta potential was from -36.6 to -62.0mV. Embelin was successfully incorporated into lipid nanospheres with entrapment efficiency about 99%. There was no interaction between embelin and selected liquid lipids which was confirmed by FTIR studies. In vitro drug release studies performed using Franz diffusion cell and results showed sustained release of embelin. Embelin LNs were stabilized with egg and soya lecithin, embelin release from these LNs followed Higuchi model and first order model, respectively, however mechanism of drug release in both LNs was non-Fickian. In vivo studies were carried out using acetic acid induced ulcerative colitis rat model and results revealed that treatment with embelin LNs significantly reduced clinical activity and macroscopic scores compared to embelin conventional suspension. Treatment with embelin LNs decreased MPO, LDH and LPO levels, increased reduced GSH levels which indicated better treatment of ulcerative colitis was achieved. This was also confirmed by improved histopathological conditions. Thus embelin LNs could be favourably used for treatment of ulcerative colitis. PMID:25957524

  15. Growth in Egg Yolk Enhances Salmonella Enteritidis Colonization and Virulence in a Mouse Model of Human Colitis.

    PubMed

    Moreau, Matthew R; Wijetunge, Dona Saumya S; Bailey, Megan L; Gongati, Sudharsan R; Goodfield, Laura L; Hewage, Eranda Mangala K Kurundu; Kennett, Mary J; Fedorchuk, Christine; Ivanov, Yury V; Linder, Jessica E; Jayarao, Bhushan M; Kariyawasam, Subhashinie

    2016-01-01

    Salmonella Enteritidis (SE) is one of the most common causes of bacterial food-borne illnesses in the world. Despite the SE's ability to colonize and infect a wide-range of host, the most common source of infection continues to be the consumption of contaminated shell eggs and egg-based products. To date, the role of the source of SE infection has not been studied as it relates to SE pathogenesis and resulting disease. Using a streptomycin-treated mouse model of human colitis, this study examined the virulence of SE grown in egg yolk and Luria Bertani (LB) broth, and mouse feces collected from mice experimentally infected with SEE1 (SEE1 passed through mice). Primary observations revealed that the mice infected with SE grown in egg yolk displayed greater illness and disease markers than those infected with SE passed through mice or grown in LB broth. Furthermore, the SE grown in egg yolk achieved higher rates of colonization in the mouse intestines and extra-intestinal organs of infected mice than the SE from LB broth or mouse feces. Our results here indicate that the source of SE infection may contribute to the overall pathogenesis of SE in a second host. These results also suggest that reservoir-pathogen dynamics may be critical for SE's ability to establish colonization and priming for virulence potential. PMID:26939126

  16. Network modelling reveals the mechanism underlying colitis-associated colon cancer and identifies novel combinatorial anti-cancer targets.

    PubMed

    Lu, Junyan; Zeng, Hanlin; Liang, Zhongjie; Chen, Limin; Zhang, Liyi; Zhang, Hao; Liu, Hong; Jiang, Hualiang; Shen, Bairong; Huang, Ming; Geng, Meiyu; Spiegel, Sarah; Luo, Cheng

    2015-10-08

    The connection between inflammation and tumourigenesis has been well established. However, the detailed molecular mechanism underlying inflammation-associated tumourigenesis remains unknown because this process involves a complex interplay between immune microenvironments and epithelial cells. To obtain a more systematic understanding of inflammation-associated tumourigenesis as well as to identify novel therapeutic approaches, we constructed a knowledge-based network describing the development of colitis-associated colon cancer (CAC) by integrating the extracellular microenvironment and intracellular signalling pathways. Dynamic simulations of the CAC network revealed a core network module, including P53, MDM2, and AKT, that may govern the malignant transformation of colon epithelial cells in a pro-tumor inflammatory microenvironment. Furthermore, in silico mutation studies and experimental validations led to a novel finding that concurrently targeting ceramide and PI3K/AKT pathway by chemical probes or marketed drugs achieves synergistic anti-cancer effects. Overall, our network model can guide further mechanistic studies on CAC and provide new insights into the design of combinatorial cancer therapies in a rational manner.

  17. Growth in Egg Yolk Enhances Salmonella Enteritidis Colonization and Virulence in a Mouse Model of Human Colitis.

    PubMed

    Moreau, Matthew R; Wijetunge, Dona Saumya S; Bailey, Megan L; Gongati, Sudharsan R; Goodfield, Laura L; Hewage, Eranda Mangala K Kurundu; Kennett, Mary J; Fedorchuk, Christine; Ivanov, Yury V; Linder, Jessica E; Jayarao, Bhushan M; Kariyawasam, Subhashinie

    2016-01-01

    Salmonella Enteritidis (SE) is one of the most common causes of bacterial food-borne illnesses in the world. Despite the SE's ability to colonize and infect a wide-range of host, the most common source of infection continues to be the consumption of contaminated shell eggs and egg-based products. To date, the role of the source of SE infection has not been studied as it relates to SE pathogenesis and resulting disease. Using a streptomycin-treated mouse model of human colitis, this study examined the virulence of SE grown in egg yolk and Luria Bertani (LB) broth, and mouse feces collected from mice experimentally infected with SEE1 (SEE1 passed through mice). Primary observations revealed that the mice infected with SE grown in egg yolk displayed greater illness and disease markers than those infected with SE passed through mice or grown in LB broth. Furthermore, the SE grown in egg yolk achieved higher rates of colonization in the mouse intestines and extra-intestinal organs of infected mice than the SE from LB broth or mouse feces. Our results here indicate that the source of SE infection may contribute to the overall pathogenesis of SE in a second host. These results also suggest that reservoir-pathogen dynamics may be critical for SE's ability to establish colonization and priming for virulence potential.

  18. Growth in Egg Yolk Enhances Salmonella Enteritidis Colonization and Virulence in a Mouse Model of Human Colitis

    PubMed Central

    Moreau, Matthew R.; Wijetunge, Dona Saumya S.; Bailey, Megan L.; Gongati, Sudharsan R.; Goodfield, Laura L.; Hewage, Eranda Mangala K. Kurundu; Kennett, Mary J.; Fedorchuk, Christine; Ivanov, Yury V.; Linder, Jessica E.; Jayarao, Bhushan M.; Kariyawasam, Subhashinie

    2016-01-01

    Salmonella Enteritidis (SE) is one of the most common causes of bacterial food-borne illnesses in the world. Despite the SE’s ability to colonize and infect a wide-range of host, the most common source of infection continues to be the consumption of contaminated shell eggs and egg-based products. To date, the role of the source of SE infection has not been studied as it relates to SE pathogenesis and resulting disease. Using a streptomycin-treated mouse model of human colitis, this study examined the virulence of SE grown in egg yolk and Luria Bertani (LB) broth, and mouse feces collected from mice experimentally infected with SEE1 (SEE1 passed through mice). Primary observations revealed that the mice infected with SE grown in egg yolk displayed greater illness and disease markers than those infected with SE passed through mice or grown in LB broth. Furthermore, the SE grown in egg yolk achieved higher rates of colonization in the mouse intestines and extra-intestinal organs of infected mice than the SE from LB broth or mouse feces. Our results here indicate that the source of SE infection may contribute to the overall pathogenesis of SE in a second host. These results also suggest that reservoir-pathogen dynamics may be critical for SE’s ability to establish colonization and priming for virulence potential. PMID:26939126

  19. Protective immunity by oral immunization with heat-killed Shigella strains in a guinea pig colitis model.

    PubMed

    Barman, Soumik; Koley, Hemanta; Ramamurthy, Thandavarayan; Chakrabarti, Manoj Kumar; Shinoda, Sumio; Nair, Gopinath Balakrish; Takeda, Yoshifumi

    2013-11-01

    The protective efficacy of and immune response to heat-killed cells of monovalent and hexavalent mixtures of six serogroups/serotypes of Shigella strains (Shigella dysenteriae 1, Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, Shigella boydii 4, and Shigella sonnei) were examined in a guinea pig colitis model. A monovalent or hexavalent mixture containing 1 × 10(7) of each serogroup/serotype of heat-killed Shigella cells was administered orally on Days 0, 7, 14 and 21. On Day 28, the immunized animals were challenged rectally with 1 × 10(9) live virulent cells of each of the six Shigella serogroups/serotypes. In all immunized groups, significant levels of protection were observed after these challenges. The serum titers of IgG and IgA against the lipopolysaccharide of each of the six Shigella serogroups/serotypes increased exponential during the course of immunization. High IgA titers against the lipopolysaccharide of each of the six Shigella serogroups/serotypes were also observed in intestinal lavage fluid from all immunized animals. These data indicate that a hexavalent mixture of heat-killed cells of the six Shigella serogroups/serotypes studied would be a possible broad-spectrum candidate vaccine against shigellosis.

  20. Forced treadmill exercise training exacerbates inflammation and causes mortality while voluntary wheel training is protective in a mouse model of colitis.

    PubMed

    Cook, Marc D; Martin, Stephen A; Williams, Collette; Whitlock, Keith; Wallig, Matthew A; Pence, Brandt D; Woods, Jeffrey A

    2013-10-01

    The purpose of this study was to examine whether exercise training reduced inflammation and symptomology in a mouse model of colitis. We hypothesized that moderate forced treadmill running (FTR) or voluntary wheel running (VWR) would reduce colitis symptoms and colon inflammation in response to dextran sodium sulfate (DSS). Male C57Bl/6J mice were randomized to sedentary, moderate intensity FTR (8-12 m/min, 40 min, 6 weeks, 5x/week), or VWR (30 days access to wheels). DSS was given at 2% (w/v) in drinking water over 5 days. Mice discontinued exercise 24 h prior to and during DSS treatment. Colons were harvested on Days 6, 8 and 12 in FTR and Day 8 post-DSS in VWR experiments. Contrary to our hypothesis, we found that moderate FTR exacerbated colitis symptomology and inflammation as measured by significant (p<0.05) increases in diarrhea and IL-6, IL-1β, IL-17 colon gene expression. We also observed higher mortality (3/10 died vs. 0/10, p=0.07) in the FTR/DSS group. In contrast, VWR alleviated colitis symptoms and reduced inflammatory gene expression in the colons of DSS-treated mice (p<0.05). While DSS treatment reduced food/fluid intake and body weight, there was a tendency for FTR to exacerbate, and for VWR to attenuate, this effect. FTR (in the absence of DSS) increased gene expression of the chemokine and antibacterial protein CCL6 suggesting that FTR altered gut homeostasis that may be related to the exaggerated response to DSS. In conclusion, we found that FTR exacerbated, whereas VWR attenuated, symptoms and inflammation in response to DSS. PMID:23707215

  1. Complications of collagenous colitis.

    PubMed

    Freeman, Hugh-James

    2008-03-21

    Microscopic forms of colitis have been described, including collagenous colitis. This disorder generally has an apparently benign clinical course. However, a number of gastric and intestinal complications, possibly coincidental, may develop with collagenous colitis. Distinctive inflammatory disorders of the gastric mucosa have been described, including lymphocytic gastritis and collagenous gastritis. Celiac disease and collagenous sprue (or collagenous enteritis) may occur. Colonic ulceration has been associated with use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, may evolve from collagenous colitis. Submucosal "dissection", colonic fractures or mucosal tears and perforation from air insufflation during colonoscopy may occur and has been hypothesized to be due to compromise of the colonic wall from submucosal collagen deposition. Similar changes may result from increased intraluminal pressure during barium enema contrast studies. Finally, malignant disorders have also been reported, including carcinoma and lymphoproliferative disease. PMID:18350593

  2. DSS colitis promotes tumorigenesis and fibrogenesis in a choline-deficient high-fat diet-induced NASH mouse model.

    PubMed

    Achiwa, Koichi; Ishigami, Masatoshi; Ishizu, Yoji; Kuzuya, Teiji; Honda, Takashi; Hayashi, Kazuhiko; Hirooka, Yoshiki; Katano, Yoshiaki; Goto, Hidemi

    2016-01-29

    Nonalcoholic steatohepatitis (NASH) patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Several lines of evidence indicate that accumulation of lipopolysaccharide (LPS) and disruption of gut microbiota play contributory roles in HCC. Moreover, in a dextran sodium sulfate (DSS)-induced colitis model in mice, a high-fat diet increases portal LPS level and promotes hepatic inflammation and fibrosis. However, this diet-induced NASH model requires at least 50 weeks for carcinogenesis. In this study, we sought to determine whether increased intestinal permeability would aggravate liver inflammation and fibrosis and accelerate tumorigenesis in a diet-induced NASH model. Mice were fed a choline-deficient high-fat (CDHF) diet for 4 or 12 weeks. The DSS group was fed CDHF and intermittently received 1% DSS in the drinking water. Exposure to DSS promoted mucosal changes such as crypt loss and increased the number of inflammatory cells in the colon. In the DSS group, portal LPS levels were elevated at 4 weeks, and the proportions of Clostridium cluster XI in the fecal microbiota were elevated. In addition, levels of serum transaminase, number of lobular inflammatory cells, F4/80 staining-positive area, and levels of inflammatory cytokines were all elevated in the DSS group. Liver histology in the DSS group revealed severe fibrosis at 12 weeks. Liver tumors were detected in the DSS group at 12 weeks, but not in the other groups. Thus, DSS administration promoted liver tumors in a CDHF diet-induced NASH mouse over the short term, suggesting that the induction of intestinal inflammation and gut disruption of microbiota in NASH promote hepatic tumorigenesis.

  3. Advances on genetic rat models of epilepsy.

    PubMed

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoro, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2015-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: 'phenotype to gene' and 'gene to phenotype'. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies.

  4. Advances on genetic rat models of epilepsy

    PubMed Central

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoto, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2014-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: ‘phenotype to gene’ and ‘gene to phenotype’. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies. PMID:25312505

  5. Change of nitric oxide in experimental colitis and its inhibition by melatonin in vivo and in vitro

    PubMed Central

    Mei, Q; Xu, J; Xiang, L; Hu, Y; Hu, X; Xu, Z

    2005-01-01

    Aim: To investigate the change of nitric oxide (NO) in rat colitis and its inhibition by melatonin in vivo and in vitro. Methods: In vivo, rat colitis was established intracolonically with trinitrobenzenesulphonic acid (TNBS) and ethanol. The animals were randomised into five groups: control group, model group, melatonin group (2.5, 5.0, 10.0 mg/kg), and treated intracolonically with saline, saline and melatonin respectively (once a day, from day 7 after colitis was established to day 28). After the end of the experiment, the mucosal damage index (CMDI) and histology score (HS) were evaluated and the level of myeloperoxidase (MPO) and malondiadehyde (MDA) and NO in the colon tissue were measured. In vitro, the co-culture model of the inflamed colon mucosa (from the colitis) with lipopolysaccharide (LPS), and the colonocytes oxidative injury model by hydroxyl radical, were designed respectively to elucidate the inhibition of NO by melatonin. Results: After treated with TNBS/ethanol, the extent of CMDI and HS, the levels of MPO, MDA, and NO in the model group, were higher than that in the control group; melatonin ameliorated these parameters effectively. The stimulation of LPS increased the level of NO and MPO and MDA in the co-culture model of inflamed colon mucosa, and melatonin significantly reduced the level of MPO, MDA, and NO. In the coloncyte oxidative injury model by hydroxyl radical, the contents of LDH, MDA, and NO were increased; melatonin reversed this oxidative injury considerably. Conclusion: This study showed that TNBS/ethanol induced colitis was pharmacologically controlled by melatonin in vivo and in vitro. PMID:16210467

  6. A mouse model for ulcerative colitis based on NOD-scid IL2R γnull mice reconstituted with peripheral blood mononuclear cells from affected individuals.

    PubMed

    Palamides, Pia; Jodeleit, Henrika; Föhlinger, Michael; Beigel, Florian; Herbach, Nadja; Mueller, Thomas; Wolf, Eckhard; Siebeck, Matthias; Gropp, Roswitha

    2016-09-01

    Animal models reflective of ulcerative colitis (UC) remain a major challenge, and yet are crucial to understand mechanisms underlying the onset of disease and inflammatory characteristics of relapses and remission. Mouse models in which colitis-like symptoms are induced through challenge with toxins such as oxazolone, dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) have been instrumental in understanding the inflammatory processes of UC. However, these neither reflect the heterogeneous symptoms observed in the UC-affected population nor can they be used to test the efficacy of inhibitors developed against human targets where high sequence and structural similarity of the respective ligands is lacking. In an attempt to overcome these problems, we have developed a mouse model that relies on NOD-scid IL2R γ(null) mice reconstituted with peripheral blood mononuclear cells derived from UC-affected individuals. Upon challenge with ethanol, mice developed colitis-like symptoms and changes in the colon architecture, characterized by influx of inflammatory cells, edema, crypt loss, crypt abscesses and epithelial hyperplasia, as previously observed in immune-competent mice. TARC, TGFβ1 and HGF expression increased in distal parts of the colon. Analysis of human leucocytes isolated from mouse spleen revealed an increase in frequencies of CD1a+, CD64+, CD163+ and TSLPR+ CD14+ monocytes, and antigen-experienced CD44+ CD4+ and CD8+ T-cells in response to ethanol. Analysis of human leucocytes from the colon of challenged mice identified CD14+ monocytes and CD11b+ monocytes as the predominant populations. Quantitative real-time PCR (RT-PCR) analysis from distal parts of the colon indicated that IFNγ might be one of the cytokines driving inflammation. Treatment with infliximab ameliorated symptoms and pathological manifestations, whereas pitrakinra had no therapeutic benefit. Thus, this model is partially reflective of the human disease and might help

  7. A mouse model for ulcerative colitis based on NOD-scid IL2R γnull mice reconstituted with peripheral blood mononuclear cells from affected individuals

    PubMed Central

    Palamides, Pia; Jodeleit, Henrika; Föhlinger, Michael; Beigel, Florian; Herbach, Nadja; Mueller, Thomas; Wolf, Eckhard; Siebeck, Matthias

    2016-01-01

    ABSTRACT Animal models reflective of ulcerative colitis (UC) remain a major challenge, and yet are crucial to understand mechanisms underlying the onset of disease and inflammatory characteristics of relapses and remission. Mouse models in which colitis-like symptoms are induced through challenge with toxins such as oxazolone, dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) have been instrumental in understanding the inflammatory processes of UC. However, these neither reflect the heterogeneous symptoms observed in the UC-affected population nor can they be used to test the efficacy of inhibitors developed against human targets where high sequence and structural similarity of the respective ligands is lacking. In an attempt to overcome these problems, we have developed a mouse model that relies on NOD-scid IL2R γnull mice reconstituted with peripheral blood mononuclear cells derived from UC-affected individuals. Upon challenge with ethanol, mice developed colitis-like symptoms and changes in the colon architecture, characterized by influx of inflammatory cells, edema, crypt loss, crypt abscesses and epithelial hyperplasia, as previously observed in immune-competent mice. TARC, TGFβ1 and HGF expression increased in distal parts of the colon. Analysis of human leucocytes isolated from mouse spleen revealed an increase in frequencies of CD1a+, CD64+, CD163+ and TSLPR+ CD14+ monocytes, and antigen-experienced CD44+ CD4+ and CD8+ T-cells in response to ethanol. Analysis of human leucocytes from the colon of challenged mice identified CD14+ monocytes and CD11b+ monocytes as the predominant populations. Quantitative real-time PCR (RT-PCR) analysis from distal parts of the colon indicated that IFNγ might be one of the cytokines driving inflammation. Treatment with infliximab ameliorated symptoms and pathological manifestations, whereas pitrakinra had no therapeutic benefit. Thus, this model is partially reflective of the human disease and might

  8. The Healing Effect of Teucrium polium in Acetic Acid-Induced Ulcerative Colitis in the Dog as an Animal Model

    PubMed Central

    Mehrabani, Davood; Bahrami, Faranak; Hosseini, Seyed Vahid; Ashraf, Mohammad Javad; Tanideh, Nader; Rezaianzadeh, Abbas; Amini, Masoud; Amini, Afshin

    2012-01-01

    BACKGROUND Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn’s disease (CD), are debilitating and chronic disorders with unpredictable courses and complicated treatment measures. Therefore, an efficient treatment protocol seems necessary as therapeutic prophylaxis for these disorders. This study aims to determine the healing effect of Teucrium polium (T. polium) in acetic acid-induced UC in an experimental dog model. METHODS From September to December 2010, eight male (20-25 kg) crossbred dogs were used for induction of UC by 6% acetic acid, transrectally. After one week, three biopsies (10, 20 and 30 cm proximal to the anal verge) were taken from the colon of each animal for histological studies. In the presence of UC, 400 mg/kg/day of T. polium extract was administered orally and transrectally (via enema) for 30 days in six of the dogs. The remaining two dogs were used as controls and did not receive T. polium. Multiple biopsies were taken 7, 14, and 30 days after discontinuation of T. polium in the same manner as before treatment. RESULTS After administration of acetic acid, we noted the presence of multiple ulcers, diffuse inflammation, PMN infiltration in the lamina propria, glandular destruction and goblet cell depletion. Treatment with T. polium restored the colonic architecture with an increased number of healthy cells and a reduction in inflammatory cells. Damage of the surface epithelial cells and mucosal layer of the lumen were reversed, which lead to faster ulcer healing. CONCLUSION T. polium may be a treatment choice for UC and can broaden the current therapy options for UC. PMID:24829634

  9. Intestinal epithelial vitamin D receptor signaling inhibits experimental colitis.

    PubMed

    Liu, Weicheng; Chen, Yunzi; Golan, Maya Aharoni; Annunziata, Maria L; Du, Jie; Dougherty, Urszula; Kong, Juan; Musch, Mark; Huang, Yong; Pekow, Joel; Zheng, Changqing; Bissonnette, Marc; Hanauer, Stephen B; Li, Yan Chun

    2013-09-01

    The inhibitory effects of vitamin D on colitis have been previously documented. Global vitamin D receptor (VDR) deletion exaggerates colitis, but the relative anticolitic contribution of epithelial and nonepithelial VDR signaling is unknown. Here, we showed that colonic epithelial VDR expression was substantially reduced in patients with Crohn's disease or ulcerative colitis. Moreover, targeted expression of human VDR (hVDR) in intestinal epithelial cells (IECs) protected mice from developing colitis. In experimental colitis models induced by 2,4,6-trinitrobenzenesulfonic acid, dextran sulfate sodium, or CD4(+)CD45RB(hi) T cell transfer, transgenic mice expressing hVDR in IECs were highly resistant to colitis, as manifested by marked reductions in clinical colitis scores, colonic histological damage, and colonic inflammation compared with WT mice. Reconstitution of Vdr-deficient IECs with the hVDR transgene completely rescued Vdr-null mice from severe colitis and death, even though the mice still maintained a hyperresponsive Vdr-deficient immune system. Mechanistically, VDR signaling attenuated PUMA induction in IECs by blocking NF-κB activation, leading to a reduction in IEC apoptosis. Together, these results demonstrate that gut epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this anticolitic activity is independent of nonepithelial immune VDR actions.

  10. Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis.

    PubMed

    Pallio, Giovanni; Bitto, Alessandra; Pizzino, Gabriele; Galfo, Federica; Irrera, Natasha; Squadrito, Francesco; Squadrito, Giovanni; Pallio, Socrate; Anastasi, Giuseppe P; Cutroneo, Giuseppina; Macrì, Antonio; Altavilla, Domenica

    2016-01-01

    Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases. PMID:27601997

  11. Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis

    PubMed Central

    Pallio, Giovanni; Bitto, Alessandra; Pizzino, Gabriele; Galfo, Federica; Irrera, Natasha; Squadrito, Francesco; Squadrito, Giovanni; Pallio, Socrate; Anastasi, Giuseppe P.; Cutroneo, Giuseppina; Macrì, Antonio; Altavilla, Domenica

    2016-01-01

    Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases. PMID:27601997

  12. Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis

    PubMed Central

    Pallio, Giovanni; Bitto, Alessandra; Pizzino, Gabriele; Galfo, Federica; Irrera, Natasha; Squadrito, Francesco; Squadrito, Giovanni; Pallio, Socrate; Anastasi, Giuseppe P.; Cutroneo, Giuseppina; Macrì, Antonio; Altavilla, Domenica

    2016-01-01

    Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.

  13. Therapeutic effects of triptolide via the inhibition of IL-1β expression in a mouse model of ulcerative colitis

    PubMed Central

    Zhang, Haifeng; Gong, Chen; Qu, Lishuai; Ding, Xiaoling; Cao, Wei; Chen, Haiqin; Zhang, Bin; Zhou, Guoxiong

    2016-01-01

    The present study aimed to investigate the effect of triptolide (TL) on ulcerative colitis (UC) and explore the potential association between the therapeutic effects of TL and IL-1β expression using a 4,4-dimethyl-4-silapentane-1-sulfonic acid (DSS)-induced mouse model to simulate human UC. A total of 70 BALB/c female mice were randomly allocated into seven equal groups: Group A, blank control; group B, normal saline injection; group C, propylene glycol injection; group D (TL1), 0.2 mg/kg TL; group E (TL2), 0.4 mg/kg TL; group F (TL3), 0.6 mg/kg TL; and group G, dexamethasone injection. Mice activity, diet and stool characteristics were recorded daily. Mice were sacrificed by cervical dislocation on day 8, and disease activity indices, colon tissue histological scores and colonic histopathological scores were subsequently calculated. Serum levels of IL-1β were evaluated by enzyme-linked immunosorbent assay, and IL-1β expression levels were examined by reverse transcription-quantitative polymerase chain reaction with colonic mucosa specimen at the gene level and western blot analysis at the protein level. The IL-1β mRNA and protein expression levels were significantly elevated in the normal saline injection and propylene glycol injection groups compared with the blank control group and (P<0.01). In TL (TL2 and TL3)- and dexamethasone-treated mice, IL-1β expression levels were significantly decreased, as compared with the normal saline and propylene glycol injection groups (P<0.05). No significant difference was detected between TL (TL2 and TL3) and dexamethasone treatments. The results of the present study indicated that IL-1β expression was upregulated in the UC mouse model, which may be associated with the development and progression of UC. Furthermore, TL inhibited IL-1β expression, suggesting that TL may be a novel therapeutic target for the treatment of UC. PMID:27588050

  14. Anti-inflammatory effects of mannanase-hydrolyzed copra meal in a porcine model of colitis.

    PubMed

    Ibuki, Masahisa; Fukui, Kensuke; Kanatani, Hiroyuki; Mine, Yoshinori

    2014-05-01

    We evaluated the anti-inflammatory activity of mannanase-hydrolyzed copra meal (MNB), including β-1,4-mannobiose (67.8%), in a dextran sodium sulfate (DSS)-induced porcine model of intestinal inflammation. In the DSS-positive control (POS) and MNB treatment (MCM) groups, DSS was first administered to piglets via intragastric catheter for 5 days, followed by 5 days administration of saline or MCM. A negative control group (NEG) received a saline alternative to DSS and MNB. Inflammation was assessed by clinical signs, morphological and histological measurements, gut permeability and neutrophil infiltration. Local production of TNF-α and IL-6 were analyzed by ELISA, colonic and ileal inflammatory gene expressions were assessed by real time RT-PCR, and CD4+CD25+ cell populations were analyzed by flow cytometry. Crypt elongation and muscle thickness, D-mannitol gut permeation, colonic expression of the inflammatory mediators TNF-α and IL-6 and myeloperoxidase activity were significantly lower in the MCM group than in that of POS group. The mRNA levels of ileal IL-1β, IL-6, IL-17 and TNF-α were significantly lower following MCM treatment than with POS treatment.MNB exerts anti-inflammatory activity in vivo, suggesting that MNB is a novel therapeutic that may provide relief to human and animals suffering from intestinal inflammation.

  15. Anti-inflammatory effects of mannanase-hydrolyzed copra meal in a porcine model of colitis.

    PubMed

    Ibuki, Masahisa; Fukui, Kensuke; Kanatani, Hiroyuki; Mine, Yoshinori

    2014-05-01

    We evaluated the anti-inflammatory activity of mannanase-hydrolyzed copra meal (MNB), including β-1,4-mannobiose (67.8%), in a dextran sodium sulfate (DSS)-induced porcine model of intestinal inflammation. In the DSS-positive control (POS) and MNB treatment (MCM) groups, DSS was first administered to piglets via intragastric catheter for 5 days, followed by 5 days administration of saline or MCM. A negative control group (NEG) received a saline alternative to DSS and MNB. Inflammation was assessed by clinical signs, morphological and histological measurements, gut permeability and neutrophil infiltration. Local production of TNF-α and IL-6 were analyzed by ELISA, colonic and ileal inflammatory gene expressions were assessed by real time RT-PCR, and CD4+CD25+ cell populations were analyzed by flow cytometry. Crypt elongation and muscle thickness, D-mannitol gut permeation, colonic expression of the inflammatory mediators TNF-α and IL-6 and myeloperoxidase activity were significantly lower in the MCM group than in that of POS group. The mRNA levels of ileal IL-1β, IL-6, IL-17 and TNF-α were significantly lower following MCM treatment than with POS treatment.MNB exerts anti-inflammatory activity in vivo, suggesting that MNB is a novel therapeutic that may provide relief to human and animals suffering from intestinal inflammation. PMID:24430661

  16. Autofluorescence spectroscopy for multimodal tissues characterization in colitis-associated cancer murine model

    NASA Astrophysics Data System (ADS)

    Dorez, Hugo; Sablong, Raphaël.; Canaple, Laurence; Saint-Jalmes, Hervé; Gaillard, Sophie; Moussata, Driffa; Beuf, Olivier

    2015-07-01

    The purpose of this research project is to assess mice colon wall, using three optical modalities (conventional endoscopy, confocal endomicroscopy and optical spectroscopy) and endoluminal MRI. The study is done in the context of inflammatory bowel disease and colorectal cancer that represent 13% of new cases of cancer, every year in western countries. An optical spectroscopic bench (autofluorescence and reflectance) was developed with a flexible fiber probe. This latter has been combined with a mini multi-purpose rigid endoscope and a confocal endomicroscope. The optical modalities were first used in vivo on SWISS mice. Then, a specific optical a phantom (containing two layers of distinct fluorophores) was developed in order to evaluate our two-channel spectroscopic probe as a basic depth-sensitive measurement tool. The preliminary results show the feasibility to combine such modalities in the same in vivo protocol. Conventional endoscopy is useful to depict inflammation along colon wall. Confocal endomicroscopy provides high-contrasted images of microvascularization. Measured optical spectra both depend on biochemical tissue content and layered structure of the medium. The light collected from one channel is not similar to the other, in terms of intensity and spectroscopic profile as the interaction with the medium observed volume is different. A comparative analysis of the spectra based on our in vitro model exhibits a strong correlation between simple index extracted from spectral data and two main phantom characteristics (fluorophore concentrations and superficial layer thickness). This work suggests that this technique could contribute to assess tissues alterations through autofluorescence spectroscopic measurement under endoscopy.

  17. Use of a balanced dual cyclooxygenase-1/2 and 5-lypoxygenase inhibitor in experimental colitis.

    PubMed

    Pallio, Giovanni; Bitto, Alessandra; Pizzino, Gabriele; Galfo, Federica; Irrera, Natasha; Minutoli, Letteria; Arcoraci, Vincenzo; Squadrito, Giovanni; Macrì, Antonio; Squadrito, Francesco; Altavilla, Domenica

    2016-10-15

    Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) play an important role in inflammatory bowel diseases (IBDs). We investigated the effects of flavocoxid, a dual COX/LOX inhibitor, in experimental colitis induced with either dinitrobenzenesulfonic acid (DNBS) or dextrane sulphate sodium (DSS) In the first model, colitis was induced in rats by a single intra-colonic instillation (25mg in 0.8ml 50% ethanol) of DNBS; after 24h animals were randomized to receive orally twice a day, flavocoxid (10mg/kg), zileuton (50mg/kg), or celecoxib (5mg/kg). Sham animals received 0.8ml of saline by a single intra-colonic instillation. Rats were killed 4 days after induction and samples were collected for analysis. In the second model, colitis was induced in rats by the administration of 8% DSS dissolved in drinking water; after 24h animals were randomized to the same above reported treatments. Sham animals received standard drinking water. Rats were killed 5 days after induction and samples were collected for analysis. Flavocoxid, zileuton and celecoxib improved weight loss, reduced colonic myeloperoxydase activity, macroscopic and microscopic damage, and TNF-α serum levels. Flavocoxid and celecoxib also reduced malondialdheyde, 6-keto PGF1α and PGE-2 levels while flavocoxid and zileuton decreased LTB-4 levels. In addition, flavocoxid treatment improved histological features and apoptosis as compared to zileuton and celecoxib; moreover only flavocoxid reduced TXB2, thus avoiding an imbalance in eicosanoids production. Our results show that flavocoxid has protective effect in IBDs and may represents a future safe treatment for inflammatory bowel diseases.

  18. Phospholipase C gamma mediates endogenous brain-derived neurotrophic factor-regulated calcitonin gene-related peptide expression in colitis-induced visceral pain

    PubMed Central

    Hashmi, Fiza; Liu, Miao; Shen, Shanwei

    2016-01-01

    Background Visceral hypersensitivity is a complex pathophysiological paradigm with unclear mechanisms. Primary afferent neuronal plasticity marked by alterations in neuroactive compounds such as calcitonin gene-related peptide is suggested to underlie the heightened sensory responses. Signal transduction that leads to calcitonin gene-related peptide expression thereby sensory neuroplasticity during colitis remains to be elucidated. Results In a rat model with colitis induced by 2,4,6-trinitrobenzene sulfonic acid, we found that endogenously elevated brain-derived neurotrophic factor elicited an up-regulation of calcitonin gene-related peptide in the lumbar L1 dorsal root ganglia. At seven days of colitis, neutralization of brain-derived neurotrophic factor with a specific brain-derived neurotrophic factor antibody reversed calcitonin gene-related peptide up-regulation in the dorsal root ganglia. Colitis-induced calcitonin gene-related peptide transcription was also inhibited by brain-derived neurotrophic factor antibody treatment. Signal transduction studies with dorsal root ganglia explants showed that brain-derived neurotrophic factor-induced calcitonin gene-related peptide expression was mediated by the phospholipase C gamma, but not the phosphatidylinositol 3-kinase/Akt or the mitogen-activated protein kinase/extracellular signal-regulated protein kinase pathway. Application of PLC inhibitor U73122 in vivo confirmed that colitis-induced and brain-derived neurotrophic factor-mediated calcitonin gene-related peptide up-regulation in the dorsal root ganglia was regulated by the phospholipase C gamma pathway. In contrast, suppression of the phosphatidylinositol 3-kinase activity in vivo had no effect on colitis-induced calcitonin gene-related peptide expression. During colitis, calcitonin gene-related peptide also co-expressed with phospholipase C gamma but not with p-Akt. Calcitonin gene-related peptide up-regulation during colitis correlated to the activation

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

    PubMed

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

    2013-05-15

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

  20. Unique Gene Expression and MR T2 Relaxometry Patterns Define Chronic Murine Dextran Sodium Sulphate Colitis as a Model for Connective Tissue Changes in Human Crohn’s Disease

    PubMed Central

    Breynaert, Christine; Dresselaers, Tom; Perrier, Clémentine; Arijs, Ingrid; Cremer, Jonathan; Van Lommel, Leentje; Van Steen, Kristel; Ferrante, Marc; Schuit, Frans; Vermeire, Séverine; Rutgeerts, Paul; Himmelreich, Uwe; Ceuppens, Jan L.; Geboes, Karel; Van Assche, Gert

    2013-01-01

    Introduction Chronically relapsing inflammation, tissue remodeling and fibrosis are hallmarks of inflammatory bowel diseases. The aim of this study was to investigate changes in connective tissue in a chronic murine model resulting from repeated cycles of dextran sodium sulphate (DSS) ingestion, to mimic the relapsing nature of the human disease. Materials and Methods C57BL/6 mice were exposed to DSS in drinking water for 1 week, followed by a recovery phase of 2 weeks. This cycle of exposure was repeated for up to 3 times (9 weeks in total). Colonic inflammation, fibrosis, extracellular matrix proteins and colonic gene expression were studied. In vivo MRI T2 relaxometry was studied as a potential non-invasive imaging tool to evaluate bowel wall inflammation and fibrosis. Results Repeated cycles of DSS resulted in a relapsing and remitting disease course, which induced a chronic segmental, transmural colitis after 2 and 3 cycles of DSS with clear induction of fibrosis and remodeling of the muscular layer. Tenascin expression mirrored its expression in Crohn’s colitis. Microarray data identified a gene expression profile different in chronic colitis from that in acute colitis. Additional recovery was associated with upregulation of unique genes, in particular keratins, pointing to activation of molecular pathways for healing and repair. In vivo MRI T2 relaxometry of the colon showed a clear shift towards higher T2 values in the acute stage and a gradual regression of T2 values with increasing cycles of DSS. Conclusions Repeated cycles of DSS exposure induce fibrosis and connective tissue changes with typical features, as occurring in Crohn’s disease. Colonic gene expression analysis revealed unique expression profiles in chronic colitis compared to acute colitis and after additional recovery, pointing to potential new targets to intervene with the induction of fibrosis. In vivo T2 relaxometry is a promising non-invasive assessment of inflammation and fibrosis

  1. PBPK MODELING OF DELTAMETHRIN IN RATS

    EPA Science Inventory

    The pyrethroid pesticide deltamethrin is cleared nearly twice as rapidly in human liver microsomes compared to rat liver microsomes. A species difference such as this could influence the toxic potency of deltamethrin between rats and humans. PBPK modeling is a tool that can be ut...

  2. Increased lymphocyte apoptosis in mouse models of colitis upon ABT-737 treatment is dependent upon BIM expression.

    PubMed

    Lutz, C; Mozaffari, M; Tosevski, V; Caj, M; Cippà, P; McRae, B L; Graff, C L; Rogler, G; Fried, M; Hausmann, M

    2015-08-01

    Exaggerated activation of lymphocytes contributes to the pathogenesis of inflammatory bowel disease (IBD). Medical therapies are linked to the BCL-2 family-mediated apoptosis. Imbalance in BCL-2 family proteins may cause failure in therapeutic responses. We investigated the role of BCL-2 inhibitor ABT-737 for lymphocyte apoptosis in mice under inflammatory conditions. B.6129P2-interleukin (IL)-10(tm1Cgn) /J (IL-10(-/-) ) weighing 25-30 g with ongoing colitis were used. Fifty mg/kg/day ABT-737 was injected intraperitoneally (i.p.). Haematological analyses were performed with an ADVIA 2120 flow cytometer and mass cytometry with a CyTOF 2. Following i.p. administration, ABT-737 was detected in both spontaneous and acute colitis in peripheral blood (PBL) and colon tissue. Treatment led to lymphopenia. CD4(+) CD44(+) CD62L(+) central memory and CD8(+) , CD44(+) CD62L(-) central memory T cells were decreased in PBL upon ABT-737 compared to vehicle-receiving controls. Increased apoptosis upon ABT-737 was determined in blood lymphocytes, splenocytes and Peyer's patches and was accompanied by a decrease in TNF and IL-1B. ABT-737 positively altered the colonic mucosa and ameliorated inflammation, as shown by colonoscopy, histology and colon length. A decreased BIM/BCL-2 ratio or absence of BIM in both Bim(-) (/) (-) and Il10(-) (/) (-) × Bim(-) (/) (-) impeded the protective effect of ABT-737. The BIM/BCL-2 ratio decreased with age and during the course of treatment. Thus, long-term treatment resulted in adapted TNF levels and macroscopic mucosal damage. ABT-737 was efficacious in diminishing lymphocytes and ameliorating colitis in a BIM-dependent manner. Regulation of inappropriate survival of lymphocytes by ABT-737 may provide a therapeutic strategy in IBD.

  3. Ulcerative Colitis in Infancy

    PubMed Central

    Rukunuzzaman, Md; Karim, A. S. M. Bazlul

    2011-01-01

    Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder of colon. Frequency of UC is gradually increasing over few years worldwide. Prevalence is 35 to 100/100 000 people in USA, 1% of them are infants. UC develops in a genetically predisposed individual with altered intestinal immune response. An eight-month-old girl presented with loose bloody stool, growth failure, and moderate pallor. The girl was diagnosed as a case of UC by colonoscopy and biopsy. Treatment was thereafter started with immunosuppressive drugs. After initial induction therapy with parenteral steroid and infliximab, the patient is now on remission with azathioprine and mesalamine. UC is rare in Bangladesh, especially in children, and it is rarer during infancy. Several conditions like infective colitis, allergic colitis, Meckel's diverticulitis, Crohn's disease, etc. may mimic the features of UC. So, if a child presents with recurrent bloody diarrhea, UC should be considered as differential diagnosis. PMID:22064342

  4. Gravitational Biology: The Rat Model

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session JP3, the discussion focuses on the following topics: Morphology of brain, pituitary and thyroid in the rats exposed to altered gravity; Biochemical Properties of B Adrenoceptors After Spaceflight (LMS-STS78) or Hindlimb Suspension in Rats; Influence of Hypergravity on the Development of Monoaminergic Systems in the Rat Spinal Cord; A Vestibular Evoked Potentials (VsEPs) Study of the Function of the Otolith Organs in Different Head Orientations with respect to Earth Gravity Vector in the Rat; Quantitative Observations on the Structure of Selected Proprioceptive Components in Adult Rats that Underwent About Half of their Fetal Development in Space; Effects of a Nine-Day Shuttle Mission on the Development of the Neonatal Rat Nervous System, A Behavioral Study; Muscle Atrophy Associated to Microgravity in Rat, Basic Data For Countermeasures; Simulated Weightlessness by Unloading in the Rat, Results of a Time Course Study of Biochemical Events Occurring During Unloading and Lack of Effect of a rhBNP-2 Treatment on Bone Formation and Bone Mineral Content in Unloading Rats; and Cytological Mechanism of the Osteogenesis Under Microgravity Conditions.

  5. Prostaglandin E2 and reactive oxygen metabolite damage in the cecum in a pony model of acute colitis

    PubMed Central

    McConnico, Rebecca S.; Argenzio, Robert A.; Roberts, Malcolm C.

    2002-01-01

    The objective of this project was to determine early tissue biochemical events associated with increased colonic secretion during the acute stage of castor-oil-induced colitis by measuring cecal mucosal and submucosal malondialdehyde (MDA) and prostaglandin E2 (PGE2), levels in ponies. Intestinal tissue (inflamed or healthy) samples were obtained from 4 age- and sex-matched Shetland ponies. Biochemical methods were used to determine MDA and PGE2 levels in intestinal tissue samples from inflamed and healthy equine intestine. Inflamed tissue MDA and PGE2 levels increased with time after castor oil challenge and correlated with granulocyte infiltration, as determined by myeloperoxidase levels in a companion study. Elevated intestinal tissue MDA levels suggest that lipid peroxidation could be attributed to reactive oxygen metabolites (ROM) released from stimulated, recruited, and resident granulocytes. Tissue levels of MDA and PGE2 suggest a role for granulocyte-derived mediators of intestinal inflammation in the massive secretory response in cases of acute equine colitis. Tissue MDA and PGE2 levels may be useful laboratory tools to quantify and characterize intestinal secretory inflammatory responses in acute inflammatory conditions in the equine colon. PMID:11858649

  6. Gene silencing of TNF-alpha in a murine model of acute colitis using a modified cyclodextrin delivery system.

    PubMed

    McCarthy, J; O'Neill, M J; Bourre, L; Walsh, D; Quinlan, A; Hurley, G; Ogier, J; Shanahan, F; Melgar, S; Darcy, R; O'Driscoll, C M

    2013-05-28

    Inflammatory bowel disease (IBD) is a chronic relapsing inflammation of the gastrointestinal tract. The cytokine TNF-alpha (TNF-α) plays a pivotal role in mediating this inflammatory response. RNA interference (RNAi) holds great promise for the specific and selective silencing of aberrantly expressed genes, such as TNF-α in IBD. The aim of this study was to investigate the efficacy of an amphiphilic cationic cyclodextrin (CD) vector for effective TNF-α siRNA delivery to macrophage cells and to mice with induced acute-colitis. The stability of CD.siRNA was examined by gel electrophoresis in biorelevant media reflecting colonic fluids. RAW264.7 cells were transfected with CD.TNF-α siRNA, stimulated with lipopolysaccharide (LPS) and TNF-α and IL-6 responses were measured by PCR and ELISA. Female C57BL/6 mice were exposed to dextran sodium sulphate (DSS) and treated by intrarectal administration with either CD.siRNA TNF-α or a control solution. In vitro, siRNA in CD nanocomplexes remained intact and stable in both fed and fasted simulated colonic fluids. RAW264.7 cells transfected with CD.TNF-α siRNA and stimulated with LPS displayed a significant reduction in both gene and protein levels of TNF-α and IL-6. CD.TNF-α siRNA-treated mice revealed a mild amelioration in clinical signs of colitis, but significant reductions in total colon weight and colonic mRNA expression of TNF-α and IL-6 compared to DSS-control mice were detected. This data indicates the clinical potential of a local CD-based TNF-α siRNA delivery system for the treatment of IBD. PMID:23500058

  7. Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis

    PubMed Central

    Nowarski, Roni; Jackson, Ruaidhrí; Gagliani, Nicola; de Zoete, Marcel R.; Palm, Noah W.; Bailis, Will; Low, Jun Siong; Harman, Christian C.D.; Graham, Morven; Elinav, Eran; Flavell, Richard A.

    2016-01-01

    SUMMARY The intestinal mucosal barrier controlling the resident microbiome is dependent on a protective mucus layer generated by goblet cells, impairment of which is a hallmark of the inflammatory bowel disease Ulcerative Colitis. Here we show that IL-18 is critical in driving the pathologic breakdown of barrier integrity in a model of colitis. Deletion of Il18 or its receptor Il18r1 in intestinal epithelial cells (Δ/EC) conferred protection from colitis and mucosal damage in mice. In contrast, deletion of the IL-18 negative regulator Il18bp resulted in severe colitis associated with loss of mature goblet cells. Colitis and goblet cell loss were rescued in Il18bp−/−;Il18rΔ/EC mice, demonstrating that colitis severity is controlled at the level of IL-18 signaling in intestinal epithelial cells. IL-18 inhibited goblet cell maturation by regulating the transcriptional program instructing goblet cell development. These results inform on the mechanism of goblet cell dysfunction which underlies the pathology of Ulcerative Colitis. PMID:26638073

  8. The Anti-Inflammatory Activity of a Novel Fused-Cyclopentenone Phosphonate and Its Potential in the Local Treatment of Experimental Colitis

    PubMed Central

    Shifrin, Helena; Harel, Efrat; Nadler-Milbauer, Mirela; Weinstock, Marta; Srebnik, Morris

    2015-01-01

    A novel fused-cyclopentenone phosphonate compound, namely, diethyl 3-nonyl-5-oxo-3,5,6,6a-tetrahydro-1H-cyclopenta[c]furan-4-ylphosphonate (P-5), was prepared and tested in vitro (LPS-activated macrophages) for its cytotoxicity and anti-inflammatory activity and in vivo (DNBS induced rat model) for its potential to ameliorate induced colitis. Specifically, the competence of P-5 to reduce TNFα, IL-6, INFγ, MCP-1, IL-1α, MIP-1α, and RANTES in LPS-activated macrophages was measured. Experimental colitis was quantified in the rat model, macroscopically and by measuring the activity of tissue MPO and iNOS and levels of TNFα and IL-1β. It was found that P-5 decreased the levels of TNFα and the tested proinflammatory cytokines and chemokines in LPS-activated macrophages. In the colitis-induced rat model, P-5 was effective locally in reducing mucosal inflammation. This activity was equal to the activity of local treatment with 5-aminosalicylic acid. It is speculated that P-5 may be used for the local treatment of IBD (e.g., with the aid of colon-specific drug platforms). Its mode of action involves inhibition of the phosphorylation of MAPK ERK but not of p38 and had no effect on IκBα. PMID:25949237

  9. Glutaraldehyde-induced colitis

    PubMed Central

    Stein, Barry L.; Lamoureux, Esther; Miller, Mark; Vasilevsky, Carol-Ann; Julien, Lynne; Gordon, Philip H.

    2001-01-01

    Objective To describe the etiology and clinical course of acute colitis occurring after flexible endoscopy. Design Chart review. Setting A university teaching hospital. Patients Eight patients who sought assessment of potential colonic disease. Intervention Colonoscopy in 5 patients and flexible sigmoidoscopy in 3 patients. The indication for endoscopy was screening in 5 patients, cancer surveillance in 2 patients and preoperative evaluation of colon carcinoma in 1 patient. Outcome measures The relation of presenting symptoms to glutaraldehyde exposure, the response to therapy and the need for further therapy. Results All patients had abdominal pain, mucus diarrhea and rectal bleeding within 48 hours after endoscopy. Most patients reported that the symptoms started within 12 hours of the procedure. All patients were confirmed by sigmoidoscopy to have colitis within 72 hours of the first endoscopic procedure. One patient required hospitalization. In the first 7 patients several stool cultures were negative for Clostridium difficile using the cytotoxin assay by the cell culture method. Four patients had negative cultures for Yersinia, Salmonella and Shigella spp. Three patients were treated with metronidazole initially. Two patients underwent endoscopic biopsy and examination of the biopsy specimen showed fibrinoleukocytic exudate and ischemic type injury. One patient underwent the scheduled sigmoid resection within 48 hours of endoscopy for a Dukes’ stage B adenocarcinoma. Concomitant acute ischemic colitis limited to the mucosa and submucosa was noted in the resected specimen. Symptoms resolved in all patients and follow-up endoscopy revealed normal mucosa. Conclusion The entity of glutaraldehyde-induced colitis should be recognized and special attention should be given during instrument cleansing to minimize the risk of its development. PMID:11308232

  10. Management of ulcerative colitis

    PubMed Central

    Fell, John M; Muhammed, Rafeeq; Spray, Chris; Crook, Kay; Russell, Richard K

    2016-01-01

    Ulcerative colitis (UC) in children is increasing. The range of treatments available has also increased too but around 1 in 4 children still require surgery to control their disease. An up-to-date understanding of treatments is essential for all clinicians involved in the care of UC patients to ensure appropriate and timely treatment while minimising the risk of complications and side effects. PMID:26553909

  11. [Ulcerative colitis? Guidelines 2004].

    PubMed

    Siegmund, B; Zeitz, M

    2005-10-12

    Ulcerative colitis was first described in 1859 from Samuel Wilks, a physician at Guy's hospital in London. The prevalence in the high incidence areas ranges from 80 to 120/100.000/year. Ulcerative colitis is a chronic relapsing or chronic active disease which starts at the rectum and presents with a continuous inflammation. Primarily young adults are affected (20 to 40 years of age) but the disease may present at all ages, from younger than 1 year of life to the 80s. Many series show a secondary peak in incidence in the elderly. In the present review we will focus on the basic principles of the therapy with regard to the variety of disease manifestations. The therapeutic algorithms will be described separately for the induction of remission and the maintenance of remission. The localization of inflammation and disease activity represent crucial factors which have to be considered. With regard to these factors, the therapeutic regimens range from simple local therapy with aminosalicylates to systemic immunosuppressive therapy, which will in extreme cases require the administration of ciclosporin. Since ulcerative colitis is associated with an increased risk in developing colon carcinoma, medical therapy as well as endoscopic surveillance are fundamental in the prevention of carcinoma. In the end an outlook to future therapeutic targets and strategies will be provided. PMID:16245638

  12. Consensus Modeling of Oral Rat Acute Toxicity

    EPA Science Inventory

    An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

  13. A rat model for hepatitis E virus

    PubMed Central

    Mishra, Niraj; Verbeken, Erik; Ramaekers, Kaat; Dallmeier, Kai

    2016-01-01

    ABSTRACT Hepatitis E virus (HEV) is one of the prime causes of acute viral hepatitis, and chronic hepatitis E is increasingly recognized as an important problem in the transplant setting. Nevertheless, the fundamental understanding of the biology of HEV replication is limited and there are few therapeutic options. The development of such therapies is partially hindered by the lack of a robust and convenient animal model. We propose the infection of athymic nude rats with the rat HEV strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the infectivity of its capped RNA transcripts was confirmed in vitro and in vivo. Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated for in vitro antiviral studies. Interestingly, rat HEV proved to be less sensitive to the antiviral activity of α-interferon, ribavirin and mycophenolic acid than genotype 3 HEV (a strain that infects humans). As a proof-of-concept, part of the C-terminal polymerase sequence of pLA-B350/luc was swapped with its genotype 3 HEV counterpart: the resulting chimeric replicon replicated with comparable efficiency as the wild-type construct, confirming that LA-B350 strain is amenable to humanization (replacement of certain sequences or motifs by their counterparts from human HEV strains). Finally, ribavirin effectively inhibited LA-B350 replication in athymic nude rats, confirming the suitability of the rat model for antiviral studies. PMID:27483350

  14. Oleic acid, hydroxytyrosol and n-3 fatty acids collectively modulate colitis through reduction of oxidative stress and IL-8 synthesis; in vitro and in vivo studies.

    PubMed

    Reddy, K Vijay Kumar; Naidu, K Akhilender

    2016-06-01

    Our recent study has demonstrated that medium chain triglycerides (MCT) and monounsaturated fatty acids potentiate the beneficial effects of fish oil on risk factors of cardiovascular disease. In the present study, we have investigated the influence of MCT or olive oil on the protective and mucosal healing ability of fish oil in ulcerative colitis using cell simulation and animal models. Caco-2 cells grown in medium chain fatty acids enriched medium has exaggerated t-butyl hydroperoxide induced cell damage, GSH depletion, and IL-1β induced IL-8 synthesis, compared to the cells grown in oleic acid & hydroxytyrosol (OT) enriched medium. Further, combined treatment of cells with eicosapentaenoic acid, docosahexaenoic acid, and OT has remarkably attenuated the cell damage, and IL-8 synthesis, compared to individual treatments. To evaluate the effect of these lipid formulations in vivo, adult Wistar rats were fed diet enriched with high amount of medium chain triglycerides (MCT), virgin olive oil, or their combination with fish oil. Colitis was induced in rats using dextran sulfate sodium (DSS) for 7days followed by 10-days of recovery period. Rats of MCT group exhibit severe disease activity, higher levels of inflammatory cytokines in the colon compared to the olive oil group. Furthermore, there was persistent body weight loss, loose stools, higher levels of inflammatory cytokines in the rats of MCT group, even after DSS was withdrawn from drinking water. Conversely, fish oil has remarkably attenuated the DSS induced alterations in both MCT and olive oil diet groups with significantly greater effect in the olive oil group. Thus, MCT increase the susceptibility to colitis through oxidative damage and IL-8 synthesis in intestinal epithelial cells. The beneficial effects of virgin olive oil could be partially attributed to hydroxytyrosol. Combined treatment of hydroxytyrosol, oleic acid and n-3 fatty acids exhibit huge therapeutic benefits in colitis. PMID:27016717

  15. Oleic acid, hydroxytyrosol and n-3 fatty acids collectively modulate colitis through reduction of oxidative stress and IL-8 synthesis; in vitro and in vivo studies.

    PubMed

    Reddy, K Vijay Kumar; Naidu, K Akhilender

    2016-06-01

    Our recent study has demonstrated that medium chain triglycerides (MCT) and monounsaturated fatty acids potentiate the beneficial effects of fish oil on risk factors of cardiovascular disease. In the present study, we have investigated the influence of MCT or olive oil on the protective and mucosal healing ability of fish oil in ulcerative colitis using cell simulation and animal models. Caco-2 cells grown in medium chain fatty acids enriched medium has exaggerated t-butyl hydroperoxide induced cell damage, GSH depletion, and IL-1β induced IL-8 synthesis, compared to the cells grown in oleic acid & hydroxytyrosol (OT) enriched medium. Further, combined treatment of cells with eicosapentaenoic acid, docosahexaenoic acid, and OT has remarkably attenuated the cell damage, and IL-8 synthesis, compared to individual treatments. To evaluate the effect of these lipid formulations in vivo, adult Wistar rats were fed diet enriched with high amount of medium chain triglycerides (MCT), virgin olive oil, or their combination with fish oil. Colitis was induced in rats using dextran sulfate sodium (DSS) for 7days followed by 10-days of recovery period. Rats of MCT group exhibit severe disease activity, higher levels of inflammatory cytokines in the colon compared to the olive oil group. Furthermore, there was persistent body weight loss, loose stools, higher levels of inflammatory cytokines in the rats of MCT group, even after DSS was withdrawn from drinking water. Conversely, fish oil has remarkably attenuated the DSS induced alterations in both MCT and olive oil diet groups with significantly greater effect in the olive oil group. Thus, MCT increase the susceptibility to colitis through oxidative damage and IL-8 synthesis in intestinal epithelial cells. The beneficial effects of virgin olive oil could be partially attributed to hydroxytyrosol. Combined treatment of hydroxytyrosol, oleic acid and n-3 fatty acids exhibit huge therapeutic benefits in colitis.

  16. The Helsinki Rat Microsurgical Sidewall Aneurysm Model

    PubMed Central

    Marbacher, Serge; Marjamaa, Johan; Abdelhameed, Essam; Hernesniemi, Juha; Niemelä, Mika; Frösen, Juhana

    2014-01-01

    Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced into clinical practice. Furthermore, experimental models are needed to elucidate the complex aneurysm biology leading to rupture of saccular aneurysms. Several different kinds of experimental models for saccular aneurysms have been established in different species. Many of them, however, require special skills, expensive equipment, or special environments, which limits their widespread use. A simple, robust, and inexpensive experimental model is needed as a standardized tool that can be used in a standardized manner in various institutions. The microsurgical rat abdominal aortic sidewall aneurysm model combines the possibility to study both novel endovascular treatment strategies and the molecular basis of aneurysm biology in a standardized and inexpensive manner. Standardized grafts by means of shape, size, and geometry are harvested from a donor rat's descending thoracic aorta and then transplanted to a syngenic recipient rat. The aneurysms are sutured end-to-side with continuous or interrupted 9-0 nylon sutures to the infrarenal abdominal aorta. We present step-by-step procedural instructions, information on necessary equipment, and discuss important anatomical and surgical details for successful microsurgical creation of an abdominal aortic sidewall aneurysm in the rat. PMID:25350840

  17. The rat choledochojejunostomy model for microsurgical training

    PubMed Central

    Lee, Jun Suh

    2016-01-01

    Purpose The feasibility of a rat choledochojejunostomy (CJ) training model was investigated, as an introductory model to microsurgery for general surgeons. Methods Roux-en-Y CJ was performed on 20 rats. Interrupted 10-0 prolene sutures were used to perform CJ. The animals were observed for 7 days and sacrificed and examined. Results The rats were divided into 2 groups of 10 based on surgical order. The CJ time showed a significant decrease from 36.2 ± 5.6 minutes in group 1 to 29.4 ± 5.7 minutes in group 2 (P = 0.015). The bile leakage rate was 40% in group 1 and 10% in group 2. The survival time was 5.4 ± 2.2 days in group 1 and 7 days in group 2 (P = 0.049). Conclusion The rat CJ training model is a feasible introductory model for general surgeons with no previous experience in microsurgery. PMID:27186568

  18. CXCR2 knockout mice are protected against DSS-colitis-induced acute kidney injury and inflammation.

    PubMed

    Ranganathan, Punithavathi; Jayakumar, Calpurnia; Manicassamy, Santhakumar; Ramesh, Ganesan

    2013-11-15

    Organ cross talk exists in many diseases of the human and animal models of human diseases. A recent study demonstrated that inflammatory mediators can cause acute kidney injury and neutrophil infiltration in a mouse model of dextran sodium sulfate (DSS)-colitis. However, the chemokines and their receptors that may mediate distant organ effects in colitis are unknown. We hypothesized that keratinocyte chemoattractant (KC)/IL-8 receptor chemokine (C-X-C motif) ligand 2 (CXCL2) mediates DSS-colitis-induced acute kidney injury. Consistent with our hypothesis, wild-type (WT) mice developed severe colitis with DSS treatment, which was associated with inflammatory cytokine and chemokine expression and neutrophil infiltration in the colon. DSS-colitis in WT was accompanied by acute kidney injury and enhanced expression of inflammatory cytokines in the kidney. However, CXCR2 knockout mice were protected against DSS-colitis as well as acute kidney injury. Moreover, the expression of cytokines and chemokines and neutrophil infiltration was blunted in CXCR2 knockout mice in the colon and kidney. Administration of recombinant KC exacerbated DSS-colitis-induced acute kidney injury. Our results suggest that KC/IL-8 and its receptor CXCR2 are critical and major mediators of organ cross talk in DSS colitis and neutralization of CXCR2 will help to reduce the incidence of acute kidney injury due to ulcerative colitis and Crohn's disease in humans.

  19. MODELING OPERANT BEHAVIOR IN THE PARKINSONIAN RAT

    PubMed Central

    Avila, Irene; Reilly, Mark P.; Sanabria, Federico; Posadas-Sánchez, Diana; Chavez, Claudia L.; Banerjee, Nikhil; Killeen, Peter; Castañeda, Edward

    2009-01-01

    Mathematical principles of reinforcement (MPR; Killeen, 1994) is a quantitative model of operant behavior that contains 3 parameters representing motor capacity (δ), motivation (a), and short term memory (λ). The present study applied MPR to characterize the effects of bilateral infusions of 6-OHDA into the substantia nigra pars compacta in the rat, a model of Parkinson’s disease. Rats were trained to lever press under a 5-component fixed ratio (5, 15, 30, 60, and 100) schedule of food reinforcement. Rats were tested for 15 days prior to dopamine lesions and again for 15 days post-lesion. To characterize functional loss relative to lesion size, rats were grouped according to the extent and the degree of lateralization of their dopamine loss. Response rates decreased as a function of dopamine depletion, primarily at intermediate ratios. MPR accounted for 98% of variance in pre- and post-lesion response rates. Consistent with reported disruptions in motor behavior induced by dopaminergic lesions, estimates of δ increased when dopamine was severely depleted. There was no support for different estimates of a based on pre- and post-lesion performance of any lesion group, suggesting that dopamine loss has negligible effects on incentive motivation. The present study demonstrates the usefulness of combining operant techniques with a theoretical model to better understand the effects of a neurochemical manipulation. PMID:19073222

  20. Animal models of bronchopulmonary dysplasia. The term rat models.

    PubMed

    O'Reilly, Megan; Thébaud, Bernard

    2014-12-15

    Bronchopulmonary dysplasia (BPD) is the chronic lung disease of prematurity that affects very preterm infants. Although advances in perinatal care have enabled the survival of infants born as early as 23-24 wk of gestation, the challenge of promoting lung growth while protecting the ever more immature lung from injury is now bigger. Consequently, BPD remains one of the most common complications of extreme prematurity and still lacks specific treatments. Progress in our understanding of BPD and the potential of developing therapeutic strategies have arisen from large (baboons, sheep, and pigs) and small (rabbits, rats, and mice) animal models. This review focuses specifically on the use of the rat to model BPD and summarizes how the model is used in various research studies and the advantages and limitations of this particular model, and it highlights recent therapeutic advances in BPD by using this rat model.

  1. Animal models of bronchopulmonary dysplasia. The term rat models.

    PubMed

    O'Reilly, Megan; Thébaud, Bernard

    2014-12-15

    Bronchopulmonary dysplasia (BPD) is the chronic lung disease of prematurity that affects very preterm infants. Although advances in perinatal care have enabled the survival of infants born as early as 23-24 wk of gestation, the challenge of promoting lung growth while protecting the ever more immature lung from injury is now bigger. Consequently, BPD remains one of the most common complications of extreme prematurity and still lacks specific treatments. Progress in our understanding of BPD and the potential of developing therapeutic strategies have arisen from large (baboons, sheep, and pigs) and small (rabbits, rats, and mice) animal models. This review focuses specifically on the use of the rat to model BPD and summarizes how the model is used in various research studies and the advantages and limitations of this particular model, and it highlights recent therapeutic advances in BPD by using this rat model. PMID:25305248

  2. Effect of a Ropy Exopolysaccharide-Producing Bifidobacterium animalis subsp. lactis Strain Orally Administered on DSS-Induced Colitis Mice Model.

    PubMed

    Hidalgo-Cantabrana, Claudio; Algieri, Francesca; Rodriguez-Nogales, Alba; Vezza, Teresa; Martínez-Camblor, Pablo; Margolles, Abelardo; Ruas-Madiedo, Patricia; Gálvez, Julio

    2016-01-01

    Exopolysaccharide (EPS)-producing bifidobacteria, particularly Bifidobacterium animalis subsp. lactis strains, are used in the functional food industry as promising probiotics with purported beneficial effects. We used three isogenic strains of B. animalis subsp. lactis, with different EPS producing phenotypes (mucoid-ropy and non-ropy), in order to determine their capability to survive the murine gastrointestinal tract transit, as well as to evaluate their role in improving clinical outcomes in a chemically-induced colitis model. The three strains were able to survive in the intestinal tract of C57BL/6J mice during the course of the intervention study. Furthermore, the disease activity index (DAI) of the animal group treated with the ropy strain was significantly lower than of the DAI of the placebo group at the end of the treatment. However, no significant differences were found among the three strains. The analysis of several immune parameters, such as TNFα and IL-10 quantified in blood plasma and lymphocyte populations enumerated in mesenteric nodes, showed some significant variations among the four experimental animal groups. Remarkably, a higher capability of the ropy strain to increase regulatory T-cells in mesenteric lymphoid nodes was demonstrated, suggesting a higher ability of this strain to regulate inflammatory responses at mucosal level. Our data indicate that strains of B. animalis subsp. lactis producing EPS that confer a mucoid-ropy phenotype could represent promising candidates to perform further studies targeting intestinal inflammatory processes. PMID:27375589

  3. Effect of a Ropy Exopolysaccharide-Producing Bifidobacterium animalis subsp. lactis Strain Orally Administered on DSS-Induced Colitis Mice Model

    PubMed Central

    Hidalgo-Cantabrana, Claudio; Algieri, Francesca; Rodriguez-Nogales, Alba; Vezza, Teresa; Martínez-Camblor, Pablo; Margolles, Abelardo; Ruas-Madiedo, Patricia; Gálvez, Julio

    2016-01-01

    Exopolysaccharide (EPS)-producing bifidobacteria, particularly Bifidobacterium animalis subsp. lactis strains, are used in the functional food industry as promising probiotics with purported beneficial effects. We used three isogenic strains of B. animalis subsp. lactis, with different EPS producing phenotypes (mucoid-ropy and non-ropy), in order to determine their capability to survive the murine gastrointestinal tract transit, as well as to evaluate their role in improving clinical outcomes in a chemically-induced colitis model. The three strains were able to survive in the intestinal tract of C57BL/6J mice during the course of the intervention study. Furthermore, the disease activity index (DAI) of the animal group treated with the ropy strain was significantly lower than of the DAI of the placebo group at the end of the treatment. However, no significant differences were found among the three strains. The analysis of several immune parameters, such as TNFα and IL-10 quantified in blood plasma and lymphocyte populations enumerated in mesenteric nodes, showed some significant variations among the four experimental animal groups. Remarkably, a higher capability of the ropy strain to increase regulatory T-cells in mesenteric lymphoid nodes was demonstrated, suggesting a higher ability of this strain to regulate inflammatory responses at mucosal level. Our data indicate that strains of B. animalis subsp. lactis producing EPS that confer a mucoid-ropy phenotype could represent promising candidates to perform further studies targeting intestinal inflammatory processes. PMID:27375589

  4. Effect of a Ropy Exopolysaccharide-Producing Bifidobacterium animalis subsp. lactis Strain Orally Administered on DSS-Induced Colitis Mice Model.

    PubMed

    Hidalgo-Cantabrana, Claudio; Algieri, Francesca; Rodriguez-Nogales, Alba; Vezza, Teresa; Martínez-Camblor, Pablo; Margolles, Abelardo; Ruas-Madiedo, Patricia; Gálvez, Julio

    2016-01-01

    Exopolysaccharide (EPS)-producing bifidobacteria, particularly Bifidobacterium animalis subsp. lactis strains, are used in the functional food industry as promising probiotics with purported beneficial effects. We used three isogenic strains of B. animalis subsp. lactis, with different EPS producing phenotypes (mucoid-ropy and non-ropy), in order to determine their capability to survive the murine gastrointestinal tract transit, as well as to evaluate their role in improving clinical outcomes in a chemically-induced colitis model. The three strains were able to survive in the intestinal tract of C57BL/6J mice during the course of the intervention study. Furthermore, the disease activity index (DAI) of the animal group treated with the ropy strain was significantly lower than of the DAI of the placebo group at the end of the treatment. However, no significant differences were found among the three strains. The analysis of several immune parameters, such as TNFα and IL-10 quantified in blood plasma and lymphocyte populations enumerated in mesenteric nodes, showed some significant variations among the four experimental animal groups. Remarkably, a higher capability of the ropy strain to increase regulatory T-cells in mesenteric lymphoid nodes was demonstrated, suggesting a higher ability of this strain to regulate inflammatory responses at mucosal level. Our data indicate that strains of B. animalis subsp. lactis producing EPS that confer a mucoid-ropy phenotype could represent promising candidates to perform further studies targeting intestinal inflammatory processes.

  5. Clostridium difficile colitis.

    PubMed

    Trnka, Y M; Lamont, J T

    1984-01-01

    Clostridium difficile has become one of the commonest pathogens of the lower intestinal tract. This organism appears unique in that infection almost always occurs during or after antibiotic therapy, suggesting that some component of the normal microflora prevents colonization by C. difficile. Once it has overgrown in the colon, C. difficile releases several toxins which cause tissue damage and diarrhea. Infection can range from a simple self-limited diarrheal illness to fulminant colitis with perforation and megacolon. Assay of stool filtrates reveals the presence of cytotoxin in nearly all patients with antibiotic-associated pseudomembranous colitis, and in approximately one third to one half of those with less severe infections. Effective therapy is available in the form of oral vancomycin, although the expense of this antibiotic has led to the use of oral metronidazole or bacitracin, which appear to be equally efficacious and considerably cheaper. Although we have learned a great deal about C. difficile in the past decade, a number of fascinating puzzles remain. We know very little about the immune response to this organism or its toxin, or whether a vaccine might someday be feasible. Similarly, we have very little insight into what effects antibodies exert on the normal colonic flora and how these effects allow C. difficile infection in a small percentage of patients. Studies of this pathogen will undoubtedly lead to a fuller understanding of the enormously complex and still mysterious microbial ferment which lives within our gastrointestinal tract. PMID:6369936

  6. [Golimumab Therapy in Ulcerative Colitis].

    PubMed

    Moon, Won

    2016-02-01

    Ulcerative colitis is a chronic inflammatory condition of the colon, characterized by diffuse mucosal inflammation and blood-mixed diarrhea. The main treatment has been 5-aminosalicylic acid, steroid, thiopurine, and anti-tumor necrosis factor alpha (TNF-α) antibodies including infliximab, adalimumab, and golimumab. Golimumab, a new anti-TNF-α agent has been recently approved for patients with moderate to severe ulcerative colitis. Its efficacy and safety has been demonstrated in line with infliximab and adalimumab in preclinical and clinical studies. This review will focus on golimumab therapy in ulcerative colitis.

  7. On the rat model of human osteopenias and osteoporoses

    NASA Technical Reports Server (NTRS)

    Frost, Harold M.; Jee, Webster S. S.

    1992-01-01

    The idea that rats cannot model human osteopenias errs. The same mechanisms control gains in bone mass (longitudinal bone growth and modeling drifts) and losses (BMU-based remodeling), in young and aged rats and humans. Furthermore, they respond similarly in rats and man to mechanical influences, hormones, drugs and other agents.

  8. Microscopic colitis: pathologic considerations, changing dogma.

    PubMed

    Robert, Marie E

    2004-01-01

    Microscopic colitis as an entity was first recognized in 1976, and has become one of the most frequent diseases to exclude on colonic mucosal biopsies. In some pathology practices, up to 30% of colonic biopsies received are from patients in whom microscopic colitis is the clinical question. In this review, the evolution of the terminology and early studies describing the pathology of microscopic colitis are discussed. The pathology of lymphocytic and collagenous colitis is reviewed in detail, including common diagnostic pitfalls, and what is currently known about the pathogenesis of these diseases. The differential diagnosis of microscopic colitis includes other idiopathic inflammatory bowel diseases (Crohn's and ulcerative colitis), infections, and drug reactions. The distinction between these entities and microscopic colitis is discussed in detail. Finally, recent studies have revealed new histopathologic changes in microscopic colitis that challenge the currently held concepts of how microscopic colitis fits into the spectrum of inflammatory bowel diseases.

  9. Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats

    PubMed Central

    Lozano-Pérez, Antonio Abel; Rodriguez-Nogales, Alba; Ortiz-Cullera, Víctor; Algieri, Francesca; Garrido-Mesa, José; Zorrilla, Pedro; Rodriguez-Cabezas, M Elena; Garrido-Mesa, Natividad; Utrilla, M Pilar; De Matteis, Laura; de la Fuente, Jesús Martínez; Cenis, José Luis; Gálvez, Julio

    2014-01-01

    Purpose We aimed to evaluate the intestinal anti-inflammatory properties of silk fibroin nanoparticles, around 100 nm in size, when loaded with the stilbene compound resveratrol, in an experimental model of rat colitis. Methods Nanoparticles were loaded with resveratrol by adsorption. The biological effects of the resveratrol-loaded nanoparticles were tested both in vitro, in a cell culture of RAW 264.7 cells (mouse macrophages), and in vivo, in the trinitrobenzenesulfonic acid model of rat colitis, when administered intracolonically. Results The resveratrol liberation in 1× phosphate-buffered saline (PBS; pH 7.4) was characterized by fast liberation, reaching the solubility limit in 3 hours, which was maintained over a period of 80 hours. The in vitro assays revealed immunomodulatory properties exerted by these resveratrol-loaded nanoparticles since they promoted macrophage activity in basal conditions and inhibited this activity when stimulated with lipopolysaccharide. The in vivo experiments showed that after evaluation of the macroscopic symptoms, inflammatory markers, and intestinal barrier function, the fibroin nanoparticles loaded with resveratrol had a better effect than the single treatments, being similar to that produced by the glucocorticoid dexamethasone. Conclusion Silk fibroin nanoparticles constitute an attractive strategy for the controlled release of resveratrol, showing immunomodulatory properties and intestinal anti-inflammatory effects. PMID:25285004

  10. Genetics Home Reference: ulcerative colitis

    MedlinePlus

    ... colitis is unknown because many genetic and environmental factors are likely to be involved. Even though the ... Parkes M, Annese V, Hakonarson H, Radford-Smith G, Duerr RH, Vermeire S, Weersma RK, Rioux JD. Meta-analysis identifies ...

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

    PubMed

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

    2015-12-01

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

  12. Rat Model of Parkes Weber Syndrome

    PubMed Central

    Bojakowski, Krzysztof; Janusz, Gabriela; Grabowska, Iwona; Zegrocka-Stendel, Oliwia; Surowiecka-Pastewka, Agnieszka; Kowalewska, Magdalena; Maciejko, Dorota; Koziak, Katarzyna

    2015-01-01

    The Parkes Weber syndrome is a congenital vascular malformation, characterized by varicose veins, arterio-venous fistulas and overgrown limbs. No broadly accepted animal model of Parkes Weber syndrome has been described. We created side-to-side arterio-venous fistula between common femoral vessels with proximal non-absorbable ligature on common femoral vein limiting the enlargement of the vein diameter in Wistar rats. Contralateral limb was sham operated. Invasive blood pressure measurements in both iliac and inferior cava veins were performed in rats 30 days after fistula creation. Tight circumference and femoral bone length were measured. Histopathology and morphology of soleus muscle, extensor digitorum longus muscle, and the common femoral vessel were analyzed. 30 days following arterio-venous fistula creation, a statistically significant elevation of blood pressure in common iliac vein and limb overgrowth was observed. Limb enlargement was caused by muscle overgrowth, varicose veins formation and bone elongation. Arterio-venous fistula with proximal outflow limitation led to significant increase of femoral vein circumference and venous wall thickness. Our study indicates that the described rat model mimics major clinical features characteristic for the human Parkes Weber syndrome: presence of arterio-venous fistula, venous hypertension and dilatation, varicose veins formation, and the limb hypertrophy. We reveal that limb overgrowth is caused by bone elongation, muscle hypertrophy, and venous dilatation. The newly established model will permit detailed studies on the mechanisms underlying the disease and on the efficacy of novel therapeutic strategies for the Parkes Weber syndrome treatment. PMID:26217941

  13. Rat Model of Parkes Weber Syndrome.

    PubMed

    Bojakowski, Krzysztof; Janusz, Gabriela; Grabowska, Iwona; Zegrocka-Stendel, Oliwia; Surowiecka-Pastewka, Agnieszka; Kowalewska, Magdalena; Maciejko, Dorota; Koziak, Katarzyna

    2015-01-01

    The Parkes Weber syndrome is a congenital vascular malformation, characterized by varicose veins, arterio-venous fistulas and overgrown limbs. No broadly accepted animal model of Parkes Weber syndrome has been described. We created side-to-side arterio-venous fistula between common femoral vessels with proximal non-absorbable ligature on common femoral vein limiting the enlargement of the vein diameter in Wistar rats. Contralateral limb was sham operated. Invasive blood pressure measurements in both iliac and inferior cava veins were performed in rats 30 days after fistula creation. Tight circumference and femoral bone length were measured. Histopathology and morphology of soleus muscle, extensor digitorum longus muscle, and the common femoral vessel were analyzed. 30 days following arterio-venous fistula creation, a statistically significant elevation of blood pressure in common iliac vein and limb overgrowth was observed. Limb enlargement was caused by muscle overgrowth, varicose veins formation and bone elongation. Arterio-venous fistula with proximal outflow limitation led to significant increase of femoral vein circumference and venous wall thickness. Our study indicates that the described rat model mimics major clinical features characteristic for the human Parkes Weber syndrome: presence of arterio-venous fistula, venous hypertension and dilatation, varicose veins formation, and the limb hypertrophy. We reveal that limb overgrowth is caused by bone elongation, muscle hypertrophy, and venous dilatation. The newly established model will permit detailed studies on the mechanisms underlying the disease and on the efficacy of novel therapeutic strategies for the Parkes Weber syndrome treatment. PMID:26217941

  14. Lymphocytic and Collagenous Colitis.

    PubMed

    Cruz-Correa; Giardiello

    2000-06-01

    Patients with symptomatic collagenous-lymphocytic colitis should eliminate dietary secretagogues such as caffeine- or lactose-containing food from their diet. When possible, use of nonsteroidal anti-inflammatory drugs should be discontinued. If steatorrhea is documented, a low-fat diet may be helpful. In the presence of bile salt malabsorption, binding resins such as cholestyramine might be useful. Nonspecific diarrheal agents such as loperamide hydrochloride, diphenoxylate hydrochloride and atropine, deodorized tincture of opium, or codeine might prove effective in some patients. Antibacterial agents such as bismuth subsalicylate (8 chewable 262-mg tablets daily) have been effective in symptom control. Metronidazole and erythromycin achieve response rates of 60%. Sulfasalazine, at the usual dose of 2 to 4 g daily, used in collagenous-lymphocytic colitis, demonstrated cessation of diarrhea in 1 to 2 weeks for 50% of patients. Other 5-aminosalicylic (5-ASA) compounds are preferred for patients with a history of sulfa allergy, and those who experience adverse reactions to sulfasalazine. Adrenocorticoid medication is reserved for patients whose conventional treatment with sulfasalazine or 5-ASA has failed. Resolution of diarrhea has been documented in 80% to 90% of patients within 1 week of treatment, however, in most patients, long-term therapy is required. Surgical management is reserved for those patients with disease refractory to medical therapy. Colectomy with ileostomy resulted in clinical and histologic resolution in small case series. If there is no abatement of symptoms, rule out other etiologies of diarrhea such as thyroid dysfunction, celiac disease, or bacterial overgrowth. PMID:11097741

  15. Controlled delivery of a new broad spectrum antibacterial agent against colitis: In vitro and in vivo performance.

    PubMed

    Nieto-Bobadilla, M S; Siepmann, F; Djouina, M; Dubuquoy, L; Tesse, N; Willart, J-F; Dubreuil, L; Siepmann, J; Neut, C

    2015-10-01

    Coated pellets and mini-tablets were prepared containing a new broad spectrum antibacterial agent: CIN-102, a well-defined, synergistic blend of trans-cinnamaldehyde, trans-2-methoxycinnamaldehyde, cinnamyl acetate, linalool, β-caryophyllene, cineol and benzyl benzoate. The aim was to provide a new treatment method for colitis, especially for Inflammatory Bowel Disease (IBD) patients. Since the simple oral gavage of CIN-102 was not able to reduce the pathogenic bacteria involved in colitis (rat model), the drug was incorporated into multiparticulates. The idea was to minimize undesired drug release in the upper gastrointestinal tract and to control CIN-102 release in the colon, in order to optimize the resulting antibiotic concentration at the site of action. A particular challenge was the fact that CIN-102 is a volatile hydrophobic liquid. Pellet cores were prepared by extrusion-spheronization and coated with polymer blends, which are sensitive to colonic bacterial enzymes. Mini-tablets were prepared by direct compression. The release of the main compound of CIN-102 (cinnamaldehyde, 86.7% w/w) was monitored in vitro. Optimized coated pellets and mini-tablets were also tested in vivo: in seven-week-old, male mice suffering from dextran sodium sulfate induced colitis. Importantly, both types of multiparticulates were able: (i) to significantly reduce the number of luminal and mucosal enterobacteria in the mice (the levels of which are increased in the disease state), and (ii) to improve the clinical course of the intestinal inflammation (decrease in the percentages of mice with bloody stools and diarrhea). Thus, the proposed coated pellets and matrix mini-tablets allowing for controlled CIN-102 release show a promising potential for new treatment methods of colitis.

  16. Constitutive activation of epithelial TLR4 augments inflammatory responses to mucosal injury and drives colitis-associated tumorigenesis

    PubMed Central

    Fukata, Masayuki; Shang, Limin; Santaolalla, Rebeca; Sotolongo, John; Pastorini, Cristhine; España, Cecilia; Ungaro, Ryan; Harpaz, Noam; Cooper, Harry S.; Elson, Greg; Kosco-Vilbois, Marie; Zaias, Julia; Perez, Maria T.; Mayer, Lloyd; Vamadevan, Arunan S.; Lira, Sergio A.; Abreu, Maria T.

    2010-01-01

    Chronic intestinal inflammation culminates in cancer and a link to TLR4 has been suggested by our observation that TLR4 deficiency prevents colitis-associated neoplasia. In the current study, we address the effect of the aberrant activation of epithelial TLR4 on induction of colitis and colitis-associated tumor development. We take a translational approach to address the consequences of increased TLR signaling in the intestinal mucosa. Mice transgenic for a constitutively-active TLR4 under the intestine-specific villin promoter (villin-TLR4 mice) were treated with DSS for acute colitis and azoxymethane-dextran sulfate sodium. TLR4 expression was analyzed by immunohistochemistry in colonic tissue from patients with ulcerative colitis and ulcerative colitis associated cancer. The effect of an antagonist TLR4 Ab was tested in prevention of colitis-associated neoplasia in the AOM-DSS model. Villin-TLR4 mice were highly susceptible to both acute colitis and colitis-associated neoplasia. Villin-TLR4 mice had increased epithelial expression of COX-2 and mucosal PGE2 production at baseline. Increased severity of colitis in villin-TLR4 mice was characterized by enhanced expression of inflammatory mediators and increased neutrophilic infiltration. In human UC samples, TLR4 expression was upregulated in almost all CAC and progressively increases with grade of dysplasia. As a proof of principle, a TLR4/MD-2 antagonist antibody inhibited colitis-associated neoplasia in the mouse model. Our results show that regulation of TLR's can affect the outcome of both acute colitis and its consequences—cancer. Targeting TLR4 and other TLR's may ultimately play a role in prevention or treatment of colitis-associated cancer. PMID:21674704

  17. Chronic Paraspinal Muscle Injury Model in Rat

    PubMed Central

    Cho, Tack Geun; Kim, Young Baeg

    2016-01-01

    Objective The objective of this study is to establish an animal model of chronic paraspinal muscle injury in rat. Methods Fifty four Sprague-Dawley male rats were divided into experimental group (n=30), sham (n=15), and normal group (n=9). Incision was done from T7 to L2 and paraspinal muscles were detached from spine and tied at each level. The paraspinal muscles were exposed and untied at 2 weeks after surgery. Sham operation was done by paraspinal muscles dissection at the same levels and wound closure was done without tying. Kyphotic index and thoracolumbar Cobb's angle were measured at preoperative, 2, 4, 8, and 12 weeks after the first surgery for all groups. The rats were sacrificed at 4, 8, and 12 weeks after the first surgery, and performed histological examinations. Results At 4 weeks after surgery, the kyphotic index decreased, but, Cobb's angle increased significantly in the experimental group (p<0.05), and then that were maintained until the end of the experiment. However, there were no significant differences of the kyphotic index and Cobb's angle between sham and normal groups. In histological examinations, necrosis and fibrosis were observed definitely and persisted until 12 weeks after surgery. There were also presences of regenerated muscle cells which nucleus is at the center of cytoplasm, centronucleated myofibers. Conclusion Our chronic injury model of paraspinal muscles in rats shows necrosis and fibrosis in the muscles for 12 weeks after surgery, which might be useful to study the pathophysiology of the degenerative thoracolumbar kyphosis or degeneration of paraspinal muscles.

  18. Chronic Paraspinal Muscle Injury Model in Rat

    PubMed Central

    Cho, Tack Geun; Kim, Young Baeg

    2016-01-01

    Objective The objective of this study is to establish an animal model of chronic paraspinal muscle injury in rat. Methods Fifty four Sprague-Dawley male rats were divided into experimental group (n=30), sham (n=15), and normal group (n=9). Incision was done from T7 to L2 and paraspinal muscles were detached from spine and tied at each level. The paraspinal muscles were exposed and untied at 2 weeks after surgery. Sham operation was done by paraspinal muscles dissection at the same levels and wound closure was done without tying. Kyphotic index and thoracolumbar Cobb's angle were measured at preoperative, 2, 4, 8, and 12 weeks after the first surgery for all groups. The rats were sacrificed at 4, 8, and 12 weeks after the first surgery, and performed histological examinations. Results At 4 weeks after surgery, the kyphotic index decreased, but, Cobb's angle increased significantly in the experimental group (p<0.05), and then that were maintained until the end of the experiment. However, there were no significant differences of the kyphotic index and Cobb's angle between sham and normal groups. In histological examinations, necrosis and fibrosis were observed definitely and persisted until 12 weeks after surgery. There were also presences of regenerated muscle cells which nucleus is at the center of cytoplasm, centronucleated myofibers. Conclusion Our chronic injury model of paraspinal muscles in rats shows necrosis and fibrosis in the muscles for 12 weeks after surgery, which might be useful to study the pathophysiology of the degenerative thoracolumbar kyphosis or degeneration of paraspinal muscles. PMID:27651859

  19. Anthocyanin-rich fractions from red raspberries attenuate inflammation in both RAW264.7 macrophages and a mouse model of colitis

    PubMed Central

    Li, Li; Wu, Zhiqin; Yao, Lijun; Wu, Yonghou; Huang, Lian; Liu, Kan; Zhou, Xiang; Gou, Deming

    2014-01-01

    Edible berries have a broad spectrum of biomedical functions, including improving immune responses and reducing risk for chronic diseases. In this study, the anti-inflammatory activities of crude extracts (CEs), anthocyanin-rich fractions (ARFs), and des-anthocyanin fractions (DAFs) from seven berries were evaluated based on their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)/IFN-γ-activated RAW264.7 macrophages. ARFs from red raspberries (RR-ARFs) exhibited the highest efficiency in suppressing NO synthesis. The anti-inflammatory properties were also demonstrated by reducing the expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1β) and IL-6 in RAW264.7 cells. The luciferase reporter assay demonstrated that the activities of NF-κB and AP-1 signaling pathways were significantly suppressed by RR-ARFs. Further studies showed that RR-ARFs decreased the phosphorylation of IKK, IκBα, p65 and JNK and the nuclear translocation of p65 in LPS/IFN-γ-stimulated RAW264.7 cells. In a mouse colitis model, dextran sulfate sodium (DSS)-induced weight loss and histological damage were significantly ameliorated by RR-ARFs treatment. Taken together, our results indicate that RR-ARFs attenuate inflammation both in vitro and in vivo primarily by inhibiting the activation of NF-κB and MAPKs. The anti-inflammatory of RR-ARFs could be harnessed and applied in animal agriculture, drug and food industries. PMID:25167935

  20. Anthocyanin-rich fractions from red raspberries attenuate inflammation in both RAW264.7 macrophages and a mouse model of colitis.

    PubMed

    Li, Li; Wang, Liyan; Wu, Zhiqin; Yao, Lijun; Wu, Yonghou; Huang, Lian; Liu, Kan; Zhou, Xiang; Gou, Deming

    2014-08-29

    Edible berries have a broad spectrum of biomedical functions, including improving immune responses and reducing risk for chronic diseases. In this study, the anti-inflammatory activities of crude extracts (CEs), anthocyanin-rich fractions (ARFs), and des-anthocyanin fractions (DAFs) from seven berries were evaluated based on their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)/IFN-γ-activated RAW264.7 macrophages. ARFs from red raspberries (RR-ARFs) exhibited the highest efficiency in suppressing NO synthesis. The anti-inflammatory properties were also demonstrated by reducing the expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1β) and IL-6 in RAW264.7 cells. The luciferase reporter assay demonstrated that the activities of NF-κB and AP-1 signaling pathways were significantly suppressed by RR-ARFs. Further studies showed that RR-ARFs decreased the phosphorylation of IKK, IκBα, p65 and JNK and the nuclear translocation of p65 in LPS/IFN-γ-stimulated RAW264.7 cells. In a mouse colitis model, dextran sulfate sodium (DSS)-induced weight loss and histological damage were significantly ameliorated by RR-ARFs treatment. Taken together, our results indicate that RR-ARFs attenuate inflammation both in vitro and in vivo primarily by inhibiting the activation of NF-κB and MAPKs. The anti-inflammatory of RR-ARFs could be harnessed and applied in animal agriculture, drug and food industries.

  1. Myrrh attenuates oxidative and inflammatory processes in acetic acid-induced ulcerative colitis

    PubMed Central

    Fatani, Amal Jamil; Alrojayee, Fatima Salih; Parmar, Mihir Yogeshkumar; Abuohashish, Hatem Mustafa; Ahmed, Mohammed Mahboobuddin; Al-Rejaie, Salim Salih

    2016-01-01

    The pathogenesis of ulcerative colitis (UC) has been associated with a weakened antioxidant capacity and increased inflammatory processes. Myrrh is traditionally used for the treatment of inflammatory diseases due to its antioxidant and anti-inflammatory properties. The present study aimed to evaluate the effects of myrrh on an experimental rat model of UC. UC was induced in rats using acetic acid (AA) after pre-treatment with myrrh (125, 250 or 500 mg/kg/day) or mesalazine (MES; 300 mg/kg/day) for 7 days. The levels of various inflammatory cytokines, prostaglandin E2 (PGE2) and nitric oxide (NO) in the rat colon tissues were assessed. In addition, the colonic levels of thiobarbituric acid reactive substances (TBARS) and non-protein sulfhydryl groups (NP-SH), as well as the activities of superoxide dismutase (SOD) and catalase (CAT), were estimated. Furthermore, total protein (TP) contents and the levels of DNA and RNA were measured, and histopathological changes in colonic tissues were analyzed. The results indicated that the levels of pro-inflammatory cytokines, PGE2, NO and TBARS were markedly increased. By contrast, the levels of interleukin-10, NP-SH, TP and nucleic acids, and the enzymatic activities of SOD and CAT were significantly decreased in the AA model group. In addition, pretreatment with myrrh and MES was able to attenuate the impaired oxidative stress response and upregulation of inflammatory biomarkers. Furthermore, the enzymatic activities of SOD and CAT were near to normal in the myrrh and MES pretreated groups. The ability of myrrh to protect against UC was further confirmed by histopathological analysis, and the high dose of myrrh exerted an effect comparable to MES. In conclusion, the results of the present study suggested that myrrh has potent therapeutic value in the amelioration of experimental colitis in laboratory animals by downregulating the expression of proinflammatory mediators and improving endogenous antioxidative activities. PMID

  2. Ideal Experimental Rat Models for Liver Diseases

    PubMed Central

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes. PMID:26421020

  3. Paternal chronic colitis causes epigenetic inheritance of susceptibility to colitis

    PubMed Central

    Tschurtschenthaler, Markus; Kachroo, Priyadarshini; Heinsen, Femke-Anouska; Adolph, Timon Erik; Rühlemann, Malte Christoph; Klughammer, Johanna; Offner, Felix Albert; Ammerpohl, Ole; Krueger, Felix; Smallwood, Sébastien; Szymczak, Silke; Kaser, Arthur; Franke, Andre

    2016-01-01

    Inflammatory bowel disease (IBD) arises by unknown environmental triggers in genetically susceptible individuals. Epigenetic regulation of gene expression may integrate internal and external influences and may thereby modulate disease susceptibility. Epigenetic modification may also affect the germ-line and in certain contexts can be inherited to offspring. This study investigates epigenetic alterations consequent to experimental murine colitis induced by dextran sodium sulphate (DSS), and their paternal transmission to offspring. Genome-wide methylome- and transcriptome-profiling of intestinal epithelial cells (IECs) and sperm cells of males of the F0 generation, which received either DSS and consequently developed colitis (F0DSS), or non-supplemented tap water (F0Ctrl) and hence remained healthy, and of their F1 offspring was performed using reduced representation bisulfite sequencing (RRBS) and RNA-sequencing (RNA-Seq), respectively. Offspring of F0DSS males exhibited aberrant methylation and expression patterns of multiple genes, including Igf1r and Nr4a2, which are involved in energy metabolism. Importantly, DSS colitis in F0DSS mice was associated with decreased body weight at baseline of their F1 offspring, and these F1 mice exhibited increased susceptibility to DSS-induced colitis compared to offspring from F0Ctrl males. This study hence demonstrates epigenetic transmissibility of metabolic and inflammatory traits resulting from experimental colitis. PMID:27538787

  4. Paternal chronic colitis causes epigenetic inheritance of susceptibility to colitis.

    PubMed

    Tschurtschenthaler, Markus; Kachroo, Priyadarshini; Heinsen, Femke-Anouska; Adolph, Timon Erik; Rühlemann, Malte Christoph; Klughammer, Johanna; Offner, Felix Albert; Ammerpohl, Ole; Krueger, Felix; Smallwood, Sébastien; Szymczak, Silke; Kaser, Arthur; Franke, Andre

    2016-01-01

    Inflammatory bowel disease (IBD) arises by unknown environmental triggers in genetically susceptible individuals. Epigenetic regulation of gene expression may integrate internal and external influences and may thereby modulate disease susceptibility. Epigenetic modification may also affect the germ-line and in certain contexts can be inherited to offspring. This study investigates epigenetic alterations consequent to experimental murine colitis induced by dextran sodium sulphate (DSS), and their paternal transmission to offspring. Genome-wide methylome- and transcriptome-profiling of intestinal epithelial cells (IECs) and sperm cells of males of the F0 generation, which received either DSS and consequently developed colitis (F0(DSS)), or non-supplemented tap water (F0(Ctrl)) and hence remained healthy, and of their F1 offspring was performed using reduced representation bisulfite sequencing (RRBS) and RNA-sequencing (RNA-Seq), respectively. Offspring of F0(DSS) males exhibited aberrant methylation and expression patterns of multiple genes, including Igf1r and Nr4a2, which are involved in energy metabolism. Importantly, DSS colitis in F0(DSS) mice was associated with decreased body weight at baseline of their F1 offspring, and these F1 mice exhibited increased susceptibility to DSS-induced colitis compared to offspring from F0(Ctrl) males. This study hence demonstrates epigenetic transmissibility of metabolic and inflammatory traits resulting from experimental colitis. PMID:27538787

  5. MODELING VOLATILE ORGANIC COMPOUND PHARMACOKINETICS IN RAT PUPS

    EPA Science Inventory

    PBPK model predictions of internal dosimetry in young rats were compared to adult animals for benzene, chloroform (CHL), methylene chloride, methyl ethly ketone (MEK), perchloroethylene, and trichloroethylene.

  6. Microscopic Colitis (Lymphocytic and Collagenous), Eosinophilic Colitis, and Celiac Disease

    PubMed Central

    Villanueva, M. Sophia; Alimi, Yewande

    2015-01-01

    Multiple tests are needed to diagnose a patient with noninfectious diarrhea. Some patients will be mistakenly labeled as diarrhea-predominant irritable bowel syndrome (IBS-D) because of nonspecific computed tomographic scans and grossly normal endoscopic findings. It is crucial to understand other less common pathologies to avoid these instances of misdiagnosis. This article focuses on microscopic colitis (MC), eosinophilic colitis (EC), and celiac disease. MC is an inflammatory condition of the colon that presents with two subtypes, only to be differentiated by histology. EC is a rare chronic inflammatory process. Depending on the extent of the disease, it can present with mild diarrhea, malabsorption, or at its worst, cause obstruction and perforation. Celiac disease affects the small bowel, but interestingly can present similarly to colitis. Both MC and EC respond to oral budesonide. Patients with celiac disease improve on gluten-free diets. These treatments are distinctly different from typical IBS-D care plans. PMID:26034409

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

    PubMed Central

    Jang, Jong-Chan; Lee, Kang Min

    2016-01-01

    We examined the protective effects of Angelica acutiloba Kitagawa (AAK) extract on a murine model of acute experimental colitis. Colitis was induced by 4% dextran sulfate sodium (DSS) in the drinking water of male C57BL/6 mice, for 7 consecutive days. Oral administration of AAK extract (500 mg/kg/day) significantly alleviated DSS-induced symptoms such as anorexia, weight loss, events of diarrhea or bloody stools, and colon shortening. Histological damage was also ameliorated, as evidenced by the architectural preservation and suppression of inflammatory cell infiltration in colonic samples. Treatment improved the colonic mRNA expression of different inflammatory markers: cytokines, inducible enzymes, matrix metalloproteinases, and tight junction-related proteins. In the isolated serum, IgE levels were downregulated. Collectively, these findings indicate the therapeutic potentials of AAK as an effective complementary or alternative modality for the treatment of ulcerative colitis. PMID:27293323

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

    PubMed

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

    2016-01-01

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

  9. Protective role of cyclooxygenase inhibitors in the adverse action of passive cigarette smoking on the initiation of experimental colitis in rats.

    PubMed

    Guo, X; Liu, E S; Ko, J K; Wong, B C; Ye, Y; Lam, S; Cho, C

    2001-01-01

    Clinical and experimental findings had indicated that cigarette smoke exposure, and cyclooxygenase-2, are strongly associated with inflammatory bowel disease. The present study aimed to evaluate the role of cyclooxygenase-2 in the pathogenesis of experimental inflammatory bowel disease as well as in the adverse action of cigarette-smoke exposure. Rats were pretreated with different cyclooxygenase-2 inhibitors (indomethacin, nimesulide, or SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide)) along with cigarette-smoke exposure before 2,4,6-trinitrobenzenesulfonic acid-enema. Results indicated that pretreatment with cyclooxygenase-2 inhibitors not only protected against 2,4,6-trinitrobenzenesulfonic acid-induced inflammatory bowel disease, but also attenuated the potentiating effect of cigarette-smoke exposure on colonic damage. Furthermore, the colonic cyclooxygenase-2 protein and mRNA expression was markedly induced by 2,4,6-trinitrobenzenesulfonic acid-enema, and it was potentiated further by cigarette-smoke exposure, while the cyclooxygenase-1 expression was not changed. The present study suggests that the highly induced cyclooxygenase-2 expression not only plays a pathogenic role in 2,4,6-trinitrobenzenesulfonic acid-induced inflammatory bowel disease, but also contributes to the adverse action of cigarette-smoke exposure on this disorder.

  10. Colonic biogeography in health and ulcerative colitis.

    PubMed

    Lavelle, Aonghus; Lennon, Grainne; Winter, Desmond C; O'Connell, P Ronan

    2016-09-01

    The relevance of biogeography to the distal gut microbiota has been investigated in both health and inflammatory bowel disease (IBD), however multiple factors, including sample type and methodology, microbiota characterization and interpersonal variability make the construction of a core model of colonic biogeography challenging. In addition, how phylogenetic classification relates to immunogenicity and whether consistent alterations in the microbiota are associated with ulcerative colitis (UC) remain open questions. This addendum seeks to review the human colonic microbiota in health and UC as currently understood, in the broader context of the human microbiome. PMID:27662587

  11. Maintaining adequate nutrition, not probiotic administration, prevents growth stunting and maintains skeletal muscle protein synthesis rates in a piglet model of colitis.

    PubMed

    Harding, Scott V; Adegoke, Olasunkanmi A J; Fraser, Keely G; Marliss, Errol B; Chevalier, Stéphanie; Kimball, Scot R; Jefferson, Leonard S; Wykes, Linda J

    2010-03-01

    Malnutrition and cytokine-induced catabolism are pervasive in children with inflammatory bowel diseases (IBD), however, the benefits of aggressive nutrition support or of probiotics on nutrient and functional deficiencies and growth remain unclear. Piglets with dextran sulfate (DS)-induced colitis consuming a 50% macronutrient restricted diet (C-MR) were compared with those receiving probiotics (C-MRP) or adequate nutrition (C-WN) and with healthy well-nourished controls (REF). C-WN versus REF had reduced growth (-34% chest circumference and -22% snout-to-rump length gain) and a tendency toward lesser weight gain, but no differences in skeletal muscle protein fractional synthesis rates (FSR) or initiation of translation via the mTOR pathway were observed. Compared with C-WN, the C-MR and C-MRP piglets had lower weight gain, growth, and skeletal muscle FSR, and lower phosphorylated p70S6K1 with higher eIF4E*4E-BP1, indicative of reduced initiation of protein translation. Finally, plasma leucine concentrations were positively correlated with weight and phosphorylated p70S6K1, whereas negatively correlated with eIF4E*4E-BP1. In conclusion, reductions in weight gain, growth, protein turnover, skeletal muscle FSR, and initiation of protein translation with moderate macronutrient restriction in colitis are not ameliorated by probiotic supplementation. However, maintaining adequate nutrient intake during colitis preserves whole body protein metabolism, but growth remains compromised.

  12. Rosmarinus officinalis L. extract ameliorates intestinal inflammation through MAPKs/NF-κB signaling in a murine model of acute experimental colitis.

    PubMed

    Medicherla, Kanakaraju; Ketkar, Avanee; Sahu, Bidya Dhar; Sudhakar, Godi; Sistla, Ramakrishna

    2016-07-13

    We investigated the anti-inflammatory and anti-colitis effects of Rosmarinus officinalis L. extract (RE) by using both in vitro LPS-activated mouse RAW 264.7 macrophages and in vivo dextran sulfate sodium (DSS)-induced experimental murine colitis and suggested the underlying possible mechanisms. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis was performed to identify the major components present in the RE. The clinical signs, biochemistry, immunoblot, ELISA and histology in colon tissues were assessed in order to elucidate the beneficial effect of RE. RE suppressed the LPS-induced pro-inflammatory cytokine production and the expressions of inflammatory proteins in macrophages. Administration of RE (50 and 100 mg kg(-1)) also significantly reduced the severity of DSS-induced murine colitis, as assessed by the clinical symptoms, colon length and histology. RE administration prevented the DSS-induced activation of p38, ERK and JNK MAPKs, attenuated IκBα phosphorylation and subsequent nuclear translocation and DNA binding of NF-κB (p65). RE also suppressed the COX-2 and iNOS expressions, decreased the levels of TNF-α and IL-6 cytokines and the myeloperoxidase activity in the colon tissue. Histological observation revealed that RE administration alleviated mucosal damage and inflammatory cell infiltration induced by DSS in the colon tissue. Hence, RE could be used as a new preventive and therapeutic food ingredient or as a dietary supplement for inflammatory bowel disease. PMID:27349640

  13. Rat Carotid Artery Balloon Injury Model

    PubMed Central

    Tulis, David Anthony

    2010-01-01

    i. Summary Numerous and diverse experimental animal models have been used over the years to examine reactions to various forms of blood vessel disease and/or injury across species and in multiple vascular beds in a cumulative effort to relate these findings to the human condition. In this context, the rat carotid artery balloon injury model is highly characterized and commonly used for investigating gross morphological, cellular, biochemical, and molecular components of the response to experimentally-induced arterial injury. The mechanical damage caused by the balloon catheter completely removes the intimal endothelial lining and creates a distending mural injury in the operated vessel. This elicits a reproducible remodeling response characterized by vascular smooth muscle cell (SMC) mitogenesis and migration (via phenotypic switching), SMC apoptosis, partial vascular endothelial cell regeneration, enhanced matrix synthesis, and establishment of an invasive neointima in time-dependent fashion. This multi-factorial process allows for investigation of these many important pathophysiological processes and can serve as a valuable “proof-of-concept” tool to verify and substantiate in vitro results; however, inherent anatomical and adaptive constraints of this in vivo model ration comparison to the diseased human system (see Note 1). In this chapter, brief overview of the materials needed and the methodologies commonly employed for successful routine performance of this important experimental animal model will be provided. Individual sub-sections will cover animal care and handling, pre- and post-operative procedures, and the surgery proper. Protocols for histopathology and morphometry and procedures for data management and interpretation pertinent to the rat carotid artery balloon injury model will be discussed in Chapter __ of this series. Notes will conclude with important caveats, limitations, and considerations for practical use of this technique. PMID:18287662

  14. Chemically Defined Diet Alters the Protective Properties of Fructo-Oligosaccharides and Isomalto-Oligosaccharides in HLA-B27 Transgenic Rats

    PubMed Central

    Valcheva, Rosica; Gänzle, Michael G.; Dieleman, Levinus A.

    2014-01-01

    Non-digestible oligosaccharides (NDO) were shown to reduce inflammation in experimental colitis, but it remains unclear whether microbiota changes mediate their colitis-modulating effects. This study assessed intestinal microbiota and intestinal inflammation after feeding chemically defined AIN-76A or rat chow diets, with or without supplementation with 8 g/kg body weight of fructo-oligosaccharides (FOS) or isomalto-oligosaccharides (IMO). The study used HLA-B27 transgenic rats, a validated model of inflammatory bowel disease (IBD), in a factorial design with 6 treatment groups. Intestinal inflammation and intestinal microbiota were analysed after 12 weeks of treatment. FOS and IMO reduced colitis in animals fed rat chow, but exhibited no anti-inflammatory effect when added to AIN-76A diets. Both NDO induced specific but divergent microbiota changes. Bifidobacteria and Enterobacteriaceae were stimulated by FOS, whereas copy numbers of Clostridium cluster IV were decreased. In addition, higher concentrations of total short-chain fatty acids (SCFA) were observed in cecal contents of rats on rat chow compared to the chemically defined diet. AIN-76A increased the relative proportions of propionate, iso-butyrate, valerate and iso-valerate irrespective of the oligosaccharide treatment. The SCFA composition, particularly the relative concentration of iso-butyrate, valerate and iso-valerate, was associated (P≤0.004 and r≥0.4) with increased colitis and IL-1 β concentration of the cecal mucosa. This study demonstrated that the protective effects of fibres on colitis development depend on the diet. Although diets modified specific cecal microbiota, our study indicates that these changes were not associated with colitis reduction. Intestinal inflammation was positively correlated to protein fermentation and negatively correlated with carbohydrate fermentation in the large intestine. PMID:25369019

  15. Apolipoprotein A-I inhibits experimental colitis and colitis-propelled carcinogenesis.

    PubMed

    Gkouskou, K K; Ioannou, M; Pavlopoulos, G A; Georgila, K; Siganou, A; Nikolaidis, G; Kanellis, D C; Moore, S; Papadakis, K A; Kardassis, D; Iliopoulos, I; McDyer, F A; Drakos, E; Eliopoulos, A G

    2016-05-12

    In both humans with long-standing ulcerative colitis and mouse models of colitis-associated carcinogenesis (CAC), tumors develop predominantly in the distal part of the large intestine but the biological basis of this intriguing pathology remains unknown. Herein we report intrinsic differences in gene expression between proximal and distal colon in the mouse, which are augmented during dextran sodium sulfate (DSS)/azoxymethane (AOM)-induced CAC. Functional enrichment of differentially expressed genes identified discrete biological pathways operating in proximal vs distal intestine and revealed a cluster of genes involved in lipid metabolism to be associated with the disease-resistant proximal colon. Guided by this finding, we have further interrogated the expression and function of one of these genes, apolipoprotein A-I (ApoA-I), a major component of high-density lipoprotein. We show that ApoA-I is expressed at higher levels in the proximal compared with the distal part of the colon and its ablation in mice results in exaggerated DSS-induced colitis and disruption of epithelial architecture in larger areas of the large intestine. Conversely, treatment with an ApoA-I mimetic peptide ameliorated the phenotypic, histopathological and inflammatory manifestations of the disease. Genetic interference with ApoA-I levels in vivo impacted on the number, size and distribution of AOM/DSS-induced colon tumors. Mechanistically, ApoA-I was found to modulate signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB activation in response to the bacterial product lipopolysaccharide with concomitant impairment in the production of the pathogenic cytokine interleukin-6. Collectively, these data demonstrate a novel protective role for ApoA-I in colitis and CAC and unravel an unprecedented link between lipid metabolic processes and intestinal pathologies.

  16. ENU mutagenesis to generate genetically modified rat models.

    PubMed

    van Boxtel, Ruben; Gould, Michael N; Cuppen, Edwin; Smits, Bart M G

    2010-01-01

    The rat is one of the most preferred model organisms in biomedical research and has been extremely useful for linking physiology and pathology to the genome. However, approaches to genetically modify specific genes in the rat germ line remain relatively scarce. To date, the most efficient approach for generating genetically modified rats has been the target-selected N-ethyl-N-nitrosourea (ENU) mutagenesis-based technology. Here, we describe the detailed protocols for ENU mutagenesis and mutant retrieval in the rat model organism.

  17. [MAM-E17 schizophrenia rat model].

    PubMed

    Kállai, Veronika; Tóth, Attila; Gálosi, Rita; Szabó, Imre; Petykó, Zoltán; Karádi, Zoltán; Kállai, János; Lénárd, László

    2015-01-01

    Schizophrenia is a serious neuropsychiatric disorder. Several brain structures, neurotransmitter systems, genetic and environmental risk factors are suspected in the background. Because of its complexity the mechanism of the disorder is not known exactly, so the treatment of patients is unsolved. In the research of schizophrenia application of the rodent models is widespread. In this study one of these models based on the effect of methylazoxymethanol- acetate (MAM) is described, which is a neurodevelopmental, validated rat model. This antimitotic agent is able to evoke a number of schizophrenic symptomes temporarily disrupting the prenatal neurogenesis. The model reproduces numerous histological and neurophysiological changes of the human disorder, moreover it also represents several behavioral and cognitive phenomena resembling those in schizophrenia. A salient advantage of the model is the demonstration of the diachronic feature of the disorder, that is, postpubertal appearance of the positive symptoms. This model provides widespread opportunities for manipulations of the symptoms, so that using it in the future investigations can lead to a better understanding of this disorder.

  18. Substance P modulates colitis-associated fibrosis.

    PubMed

    Koon, Hon Wai; Shih, David; Karagiannides, Iordanes; Zhao, Dezheng; Fazelbhoy, Zafeer; Hing, Tressia; Xu, Hua; Lu, Bao; Gerard, Norma; Pothoulakis, Charalabos

    2010-11-01

    Substance P (SP) and the neurokinin-1 receptor (NK-1R) are involved in the development of colitis and mucosal healing after colonic inflammation. We studied whether SP modulates colonic fibrosis by using a chronic model of trinitrobenzenesulfonic acid (TNBS)-induced colitis in wild-type (WT) and NK-1R-deficient (NK-1R KD) mice. We found increased mRNA expression levels of collagen, vimentin, and the fibrogenic factors transforming growth factor β1 and insulin-like growth factor 1 in the chronically inflamed colons of WT mice treated with repeated intracolonic TNBS administrations. Fibrosis in TNBS-treated mice was also evident immunohistochemically by collagen deposition in the colon. Treatment of TNBS-exposed WT mice with the NK-1R antagonist CJ-12255 reduced colonic inflammation, colonic fibrosis, fibroblast accumulation, and expression levels of the fibrogenic factors. NK-1R knockout mice chronically exposed to TNBS had similar colonic inflammation compared with WT, but reduced colonic fibrosis, fibroblast accumulation, and expression levels of fibrogenic factors. Immunohistochemical staining also showed co-localization of NK-1R with fibroblasts in inflamed colons of mice and in colonic mucosa of patients with Crohn's disease. Exposure of human colonic CCD-18Co fibroblasts to SP (10 nmol/L) increased cell migration. SP stimulated collagen synthesis in CCD-18Co fibroblasts in the presence of transforming growth factor β1 and insulin-like growth factor 1, and this effect was reduced by Akt inhibition. Thus, SP, via NK-1R, promotes intestinal fibrogenesis after chronic colitis by stimulating fibrotic responses in fibroblasts. PMID:20889569

  19. Behavioral Treatment of Mucous Colitis

    ERIC Educational Resources Information Center

    Youell, Katherine J.; McCullough, James P.

    1975-01-01

    A 22-year-old female graduate student who suffered colitis attacks at the onset of therapy was apparently successfully treated by a procedure in which the therapist labeled antecedent stress events that appeared to be precipitating the attacks. The client was then taught a behavioral coping strategy to counter the stress events. (Author)

  20. Incidence and prevalence of ulcerative colitis in Punjab, North India

    PubMed Central

    Sood, A; Midha, V; Sood, N; Bhatia, A S; Avasthi, G

    2003-01-01

    Introduction: Ulcerative colitis occurs worldwide. It is considered common in most of Europe and North America and uncommon in most of the developing Asian countries. The incidence/prevalence of ulcerative colitis varies not only according to geographical region but also with race and ethnicity. There are no reported data from India on the incidence of the disease and its prevalence. Material and methods: A house to house survey was conducted by questionnaire, formulated to enquire about symptoms that are suggestive of ulcerative colitis. Those with prolonged diarrhoea with or without rectal bleeding were considered as suspected cases. These suspected cases were subjected to video sigmoidoscopy/colonoscopy and rectal biopsy. In addition, patients already diagnosed and receiving treatment for ulcerative colitis, encountered during the survey, were reviewed. Resurvey of the same areas was conducted after a one year interval to detect new cases. Using direct methods, standardised rates were calculated using world standard population weights 22, 18, 16, 12, 12, 9, 7, 3, and 1 for each 10 year age group. Standardised rates were also obtained separately for males, females, and combined populations, using the Punjab state 1991 population census data. Rates were also estimated according to UK 2000 population data. Ninety five per cent confidence intervals (95% CI) of prevalence and incidence rates of ulcerative colitis were estimated under the assumption that the distribution of cases followed a Poisson probability model. Results: A total population of 51 910 were screened from January to March 1999. We identified 147 suspected cases and of these 23 were finally established as ulcerative colitis cases, giving a crude prevalence rate of 44.3 per 100 000 inhabitants (95% CI 29.4–66.6). A second visit to the same areas after one year identified 10 suspected cases in a population of 49 834. Of these, three were confirmed as “definite” ulcerative colitis giving a crude

  1. Experimental rat models of chronic allograft nephropathy: a review

    PubMed Central

    Shrestha, Badri; Haylor, John

    2014-01-01

    Chronic allograft nephropathy (CAN) is the leading cause of late allograft loss after renal transplantation (RT), which continues to remain an unresolved problem. A rat model of CAN was first described in 1969 by White et al. Although the rat model of RT can be technically challenging, it is attractive because the pathogenesis of CAN is similar to that following human RT and the pathological features of CAN develop within months as compared with years in human RT. The rat model of RT is considered as a useful investigational tool in the field of experimental transplantation research. We have reviewed the literature on studies of rat RT reporting the donor and recipient strain combinations that have investigated resultant survival and histological outcomes. Several different combinations of inbred and outbred rat combinations have been reported to investigate the multiple aspects of transplantation, including acute rejection, cellular and humoral rejection mechanisms and their treatments, CAN, and potential targets for its prevention. PMID:25092995

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

    PubMed

    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. PMID:27063801

  3. Heligmosomoides polygyrus bakeri infection activates colonic FoxP3+ T cells enhancing their capacity to prevent colitis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Helminthic infections protect mice from colitis in murine models of inflammatory bowel disease and also may protect people. Helminths like Heligmosomoides bakeri (Hpb) can induce Tregs. Experiments explored if Hpb infection could protect mice from colitis through activation of colonic Treg and exam...

  4. A Rat Excised Larynx Model of Vocal Fold Scar

    ERIC Educational Resources Information Center

    Welham, Nathan V.; Montequin, Douglas W.; Tateya, Ichiro; Tateya, Tomoko; Choi, Seong Hee; Bless, Diane M.

    2009-01-01

    Purpose: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. Method: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic…

  5. β-lactam-associated eosinophilic colitis.

    PubMed

    Mogilevski, Tamara; Nickless, David; Hume, Sam

    2015-01-01

    A 42-year-old man with a history of childhood asthma presented with a 2-week history of watery diarrhoea and marked peripheral eosinophilia in the setting of recent use of cephalexin. His colonoscopy revealed patchy colitis. Biopsies were consistent with eosinophilic colitis. Two months later he received a course of amoxicillin resulting in recurrence of peripheral eosinophilia. Given the time-frame of β-lactam administration to symptom onset and elimination of all other precipitating causes, he was diagnosed with β-lactam-associated eosinophilic colitis. The patient's symptoms resolved and peripheral eosinophil count decreased with no specific treatment. Eosinophilic colitis is a rare heterogeneous condition, the pathogenesis of which is likely to be an interplay between environmental and genetic factors. It can be secondary to a helminthic infection or a drug reaction and has been associated with ulcerative colitis. If secondary causes of eosinophilic colitis have been excluded, the mainstay of treatment is with corticosteroids. PMID:26106168

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

    PubMed Central

    Lean, Qi Ying; Eri, Rajaraman D.; Randall-Demllo, Sarron; Sohal, Sukhwinder Singh; Stewart, Niall; Peterson, Gregory M.; Gueven, Nuri; Patel, Rahul P.

    2015-01-01

    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. PMID:26218284

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

    PubMed

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

    2014-12-01

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

  8. Vitamin D treatment attenuates 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis but not oxazolone-induced colitis

    PubMed Central

    Liu, Tianjing; Shi, Yongyan; Du, Jie; Ge, Xin; Teng, Xu; Liu, Lu; Wang, Enbo; Zhao, Qun

    2016-01-01

    Crohn’s disease (CD) and ulcerative colitis (UC) have different immunological mechanisms, while both of them are potential targets of vitamin D treatment. In this study, we have tried to address the role of vitamin D in CD and UC using two mouse models. Mice of C57B6L were given vitamin D before the induction of colitis. Our results showed that vitamin D attenuated 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis but not oxazolone-induced colitis. Vitamin D could preserve the local histology, alleviate inflammation, suppress apoptosis, maintain tight junction function and decrease permeability. Interestingly, it has more of an effect on local structure preservation and inflammation inhibition in CD than in UC mice. Vitamin D blocked the increase of helper T-cell type 1 (Th1)- and helper T-cell type 17 (Th17)-related cytokines in TNBS-induced colitis. But the increase of helper T-cell type 2 (Th2)- and regulatory T cells (Treg)-related cytokines was augmented at the same time in oxazolone-induced colitis which counteracted each other. Our study helps elucidate the differential protective effects of vitamin D on CD and UC patients, as reported in literature. PMID:27620138

  9. Vitamin D treatment attenuates 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis but not oxazolone-induced colitis.

    PubMed

    Liu, Tianjing; Shi, Yongyan; Du, Jie; Ge, Xin; Teng, Xu; Liu, Lu; Wang, Enbo; Zhao, Qun

    2016-01-01

    Crohn's disease (CD) and ulcerative colitis (UC) have different immunological mechanisms, while both of them are potential targets of vitamin D treatment. In this study, we have tried to address the role of vitamin D in CD and UC using two mouse models. Mice of C57B6L were given vitamin D before the induction of colitis. Our results showed that vitamin D attenuated 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis but not oxazolone-induced colitis. Vitamin D could preserve the local histology, alleviate inflammation, suppress apoptosis, maintain tight junction function and decrease permeability. Interestingly, it has more of an effect on local structure preservation and inflammation inhibition in CD than in UC mice. Vitamin D blocked the increase of helper T-cell type 1 (Th1)- and helper T-cell type 17 (Th17)-related cytokines in TNBS-induced colitis. But the increase of helper T-cell type 2 (Th2)- and regulatory T cells (Treg)-related cytokines was augmented at the same time in oxazolone-induced colitis which counteracted each other. Our study helps elucidate the differential protective effects of vitamin D on CD and UC patients, as reported in literature. PMID:27620138

  10. Collagenous gastroduodenitis on collagenous colitis.

    PubMed

    Stolte, M; Ritter, M; Borchard, F; Koch-Scherrer, G

    1990-07-01

    We report on a case of collagenous gastroduodenitis with concomitant collagenous colitis in a 75-year-old woman with watery diarrhea of approximately six months' standing. The step biopsy material obtained from the colon revealed continuous collagenous colitis with thickening of the basal membrane to 30 microns. The biopsies taken from the stomach and duodenum also revealed a band-like deposition of collagen in the duodenum (bulb and proximal portion of the descending portion) along the basal membrane of the lining epithelium, associated with partial atrophy of the villi. In the stomach, this band of collagen was located, parallel to the mucosal surface, at the level of the floor of the foveolae. PMID:2209504

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

    PubMed Central

    Fan, Heng; Tang, Qing; Shou, Zhe-Xing; Zuo, Dong-Mei; Zou, Zhou; Xu, Meng; Chen, Qian-Yun; Peng, Ying; Deng, Shuang-Jiao; Liu, Yu-Jin

    2015-01-01

    The administration of bone mesenchymal stem cells (BMSCs) could reverse experimental colitis, and the predominant mechanism in tissue repair seems to be related to their paracrine activity. BMSCs derived extracellular vesicles (BMSC-EVs), including mcirovesicles and exosomes, containing diverse proteins, mRNAs and micro-RNAs, mediating various biological functions, might be a main paracrine mechanism for stem cell to injured cell communication. We aimed to investigate the potential alleviating effects of BMSC-EVs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Intravenous injection of BMSC-EVs attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI) and histological colonic damage. In inflammation response, the BMSC-EVs treatment significantly reduced both the mRNA and protein levels of nuclear factor kappaBp65 (NF-κBp65), tumor necrosis factor-alpha (TNF-α), induciblenitric oxidesynthase (iNOS) and cyclooxygenase-2 (COX-2) in injured colon. Additionally, the BMSC-EVs injection resulted in a markedly decrease in interleukin-1β (IL-1β) and an increase in interleukin-10 (IL-10) expression. Therapeutic effect of BMSC-EVs associated with suppression of oxidative perturbations was manifested by a decrease in the activity of myeloperoxidase (MPO) and Malondialdehyde (MDA), as well as an increase in superoxide dismutase (SOD) and glutathione (GSH). BMSC-EVs also suppressed the apoptosis via reducing the cleavage of caspase-3, caspase-8 and caspase-9 in colitis rats. Data obtained indicated that the beneficial effects of BMSC-EVs were due to the down regulation of pro-inflammatory cytokines levels, inhibition of NF-κBp65 signal transduction pathways, modulation of anti-oxidant/ oxidant balance, and moderation of the occurrence of apoptosis. PMID:26469068

  12. Oral administration of dextran sodium sulphate induces a caecum-localized colitis in rabbits.

    PubMed

    Leonardi, Irina; Nicholls, Flora; Atrott, Kirstin; Cee, Alexandra; Tewes, Bernhard; Greinwald, Roland; Rogler, Gerhard; Frey-Wagner, Isabelle

    2015-06-01

    Trichuris suis ova (TSO) have shown promising results in the treatment of inflammatory bowel disease (IBD) but the mechanisms which underlies this therapeutic effect cannot be studied in mice and rats as T. suis fails to colonize the rodent intestine, whilst hatching in humans and rabbits. As a suitable rabbit IBD model is currently not available, we developed a rabbit colitis model by administration of dextran sodium sulphate (DSS). White Himalayan rabbits (n = 12) received 0.1% DSS in the daily water supply for five days. Clinical symptoms were monitored daily, and rabbits were sacrificed at different time points. A genomewide expression analysis was performed with RNA isolated from caecal lamina propria mononuclear cells (LPMC) and intestinal epithelial cells (IEC). The disease activity index of DSS rabbits increased up to 2.1 ± 0.4 (n = 6) at day 10 (controls <0.5). DSS induced a caecum-localized pathology with crypt architectural distortion, stunted villous surface and inflammatory infiltrate in the lamina propria. The histopathology score reached a peak of 14.2 ± 4.9 (n = 4) at day 10 (controls 7.7 ± 0.9, n = 5). Expression profiling revealed an enrichment of IBD-related genes in both LPMC and IEC. Innate inflammatory response, Th17 signalling and chemotaxis were among the pathways affected significantly. We describe a reproducible and reliable rabbit model of DSS colitis. Localization of the inflammation in the caecum and its similarities to IBD make this model particularly suitable to study TSO therapy in vivo.

  13. Induction of IDO-1 by immunostimulatory DNA limits severity of experimental colitis.

    PubMed

    Ciorba, Matthew A; Bettonville, Ellen E; McDonald, Keely G; Metz, Richard; Prendergast, George C; Newberry, Rodney D; Stenson, William F

    2010-04-01

    The chronic inflammatory bowel diseases are characterized by aberrant innate and adaptive immune responses to commensal luminal bacteria. In both human inflammatory bowel disease and in experimental models of colitis, there is an increased expression of the enzyme IDO. IDO expression has the capacity to exert antimicrobial effects and dampen adaptive immune responses. In the murine trinitrobenzene sulfonic acid model of colitis, inhibition of this enzyme leads to worsened disease severity, suggesting that IDO acts as a natural break in limiting colitis. In this investigation, we show that induction of IDO-1 by a TLR-9 agonist, immunostimulatory (ISS) DNA, critically contributes to its colitis limiting capacities. ISS DNA induces intestinal expression of IDO-1 but not the recently described paralog enzyme IDO-2. This induction occurred in both epithelial cells and in subsets of CD11c(+) and CD11b(+) cells of the lamina propria, which also increase after ISS-oligodeoxynucleotide. Signaling required for intestinal IDO-1 induction involves IFN-dependent pathways, as IDO-1 was not induced in STAT-1 knockout mice. Using both the trinitrobenzene sulfonic acid and dextran sodium sulfate models of colitis, we show the importance of IDO-1s induction in limiting colitis severity. The clinical parameters and histological correlates of colitis in these models were improved by administration of the TLR-9 agonist; however, when the function of IDO is inhibited, the colitis limiting effects of ISS-oligodeoxynucleotide were abrogated. These findings support the possibility that targeted induction of IDO-1 is an approach deserving further investigation as a therapeutic strategy for diseases of intestinal inflammation.

  14. Transplant arteriosclerosis in a rat aortic model.

    PubMed Central

    Isik, F. F.; McDonald, T. O.; Ferguson, M.; Yamanaka, E.; Gordon, D.

    1992-01-01

    Transplant arteriosclerosis (TA) has emerged as an obstacle to the long-term survival of transplanted organs, especially cardiac transplants. The animal models that have been used to study TA have not been fully characterized with regard to features such as the time course of cell proliferation and the sequence of cell types arriving in the developing intimal lesion. We present a model of TA based on a transplanted segment of abdominal aorta that helps address these questions. Two strains of rats (PVG x DA) underwent orthotopic aortic transplantation without immunosuppression and were killed at 14, 20, 40, and 60 days after transplantation. The within-strain control group displayed minimal evidence of cellular rejection with minimal to absent intimal lesions. In contrast, the allograft group showed a linearly increasing intimal lesion, up through 60 days after transplantation. The mechanism of intimal thickening was by an increase in cell number at the earlier time points with the later deposition of extracellular matrix. The early intimal lesion consisted mostly of mononuclear inflammatory cells (45%) with gradually increasing presence of smooth muscle cells (SMC) in the intima between 20 and 60 days. Conversely, the media showed gradual infiltration by macrophage-type cells with virtual loss of all SMC from the media by 40 days. The proliferative index showed a peak of 6% and 8% at 20 days in both the intima and media, respectively, and was preceded by the presence of macrophages. In fact, most of the proliferating cells at the earlier time points were either monocytes/macrophages, or were immediately adjacent to monocyte-/macrophage-rich regions. This straight artery segment model of transplant arteriosclerosis provides an easily quantifiable system in which the effects of different interventions (e.g., immunosuppressive regimens) can be tested. Images Figure 2 Figure 3 Figure 6 Figure 7 Figure 8 Figure 9 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure

  15. Evolution of microscopic colitis to giant cell colitis without significant intraepithelial lymphocytosis or thickened collagen plate.

    PubMed

    De Petris, Giovanni; Chen, Longwen

    2015-05-01

    Microscopic colitis (MC) is an umbrella term that encompasses lymphocytic colitis (LC) and collagenous colitis (CC). Several histological variants of these 2 entities exist; among them is the uncommon giant cell colitis (GCC), in which histiocytic giant cells (GCs) are present in background of CC or LC. We report the case of a 71-year-old woman complaining of watery diarrhea for several years that was diagnosed with CC. At follow-up, she developed giant cell colitis (GCC). Nine years later, a colectomy revealed a form of microscopic colitis in which significant intraepithelial lymphocytosis and collagen plate thickening have disappeared while GCs persisted with diffuse mononuclear cells inflammation of the lamina propria. Thinning of the collagen plate in association with GCs has been described previously. The case contributes the possibility of further evolution of MC into a pure giant cell colitis in which the prototypical manifestations of MC have all but disappeared.

  16. Early Detection of T cell Transfer-induced Autoimmune Colitis by In Vivo Imaging System

    PubMed Central

    Chen, Yu-Ling; Chen, Yi-Ting; Lo, Cheng-Feng; Hsieh, Ching-I; Chiu, Shang-Yi; Wu, Chang-Yen; Yeh, Yu-Shan; Hung, Shu-Hsuan; Cheng, Po-Hao; Su, Yu-Hsuan; Jiang, Si-Tse; Chin, Hsian-Jean; Su, Yu-Chia

    2016-01-01

    Inflammatory bowel disease is a chronic and progressive inflammatory intestinal disease that includes two major types, namely ulcerative colitis and Crohn’s disease (CD). CD is characterized by intestinal epithelial hyperplasia and inflammatory cell infiltration. Transfer of CD25−CD45RBhiCD4+ (naïve) T cells into immunodeficiency mice induces autoimmune colitis with pathological lesions similar to CD and loss of body weight 4 weeks after cell transfer. However, weight loss neither has sufficient sensitivity nor totally matches the pathological findings of CD. To establish an early and sensitive indicator of autoimmune colitis model, the transferred T cell-induced colitis mouse model was modified by transferring luciferase-expressing donor T cells and determining the colitis by in vivo imaging system (IVIS). Colitis was detected with IVIS 7–10 days before the onset of body weight loss and diarrhea. IVIS was also applied in the dexamethasone treatment trial, and was a more sensitive indicator than body weight changes. All IVIS signals were parallel to the pathological abnormalities of the gut and immunological analysis results. In summary, IVIS provides both sensitive and objective means to monitor the disease course of transferred T cell-induced CD and fulfills the 3Rs principle of humane care of laboratory animals. PMID:27762297

  17. Probiotics and prebiotics in ulcerative colitis.

    PubMed

    Derikx, Lauranne A A P; Dieleman, Levinus A; Hoentjen, Frank

    2016-02-01

    The intestinal microbiota is one of the key players in the etiology of ulcerative colitis. Manipulation of this microflora with probiotics and prebiotics is an attractive strategy in the management of ulcerative colitis. Several intervention studies for both the induction and maintenance of remission in ulcerative colitis patients have been performed. Most of these studies evaluated VSL#3 or E. Coli Nissle 1917 and in general there is evidence for efficacy of these agents for induction and maintenance of remission. However, studies are frequently underpowered, lack a control group, and are very heterogeneous investigating different probiotic strains in different study populations. The absence of well-powered robust randomized placebo-controlled trials impedes the widespread use of probiotics and prebiotics in ulcerative colitis. However, given the promising results that are currently available, probiotics and prebiotics may find their way to the treatment algorithm for ulcerative colitis in the near future. PMID:27048897

  18. Study of a Monoclonal Antibody KHK4083 in Moderate Ulcerative Colitis

    ClinicalTrials.gov

    2016-09-26

    Ulcerative Colitis; Digestive System Diseases; Colitis, Ulcerative; Colitis; Gastrointestinal Diseases; Inflammatory Bowel Diseases; Intestinal Diseases; Colonic Diseases; Autoimmune Disease; Abdominal Pain

  19. Experimental models of hepatic fibrosis in the rat.

    PubMed

    Wasser, S; Tan, C E

    1999-01-01

    The rat is a frequently used experimental model in studies involving human disease. We review several methods of inducing hepatic fibrosis and cirrhosis in rats. These include induction by hepatotoxins and hepatocarcinogens such as carbon tetrachloride, dimethylnitrosamine, thioacetamide and furan; the hepatoxin-cum-nutrient, alcohol; a high fat-low choline-low protein diet; immunologic agents such as heterologous serum or bacterial cell wall products; and obstructive jaundice and biliary cirrhosis by common bile duct ligation. PMID:10374036

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

    PubMed

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

    2011-10-01

    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.

  1. Novel Rat Model for Neurocysticercosis Using Taenia solium

    PubMed Central

    Verastegui, Manuela R.; Mejia, Alan; Clark, Taryn; Gavidia, Cesar M.; Mamani, Javier; Ccopa, Fredy; Angulo, Noelia; Chile, Nancy; Carmen, Rogger; Medina, Roxana; García, Hector H.; Rodriguez, Silvia; Ortega, Ynes; Gilman, Robert H.

    2016-01-01

    Neurocysticercosis is caused by Taenia solium infecting the central nervous system and is the leading cause of acquired epilepsy and convulsive conditions worldwide. Research into the pathophysiology of the disease and appropriate treatment is hindered by lack of cost-effective and physiologically similar animal models. We generated a novel rat neurocysticercosis model using intracranial infection with activated T. solium oncospheres. Holtzman rats were infected in two separate groups: the first group was inoculated extraparenchymally and the second intraparenchymally, with different doses of activated oncospheres. The groups were evaluated at three different ages. Histologic examination of the tissue surrounding T. solium cysticerci was performed. Results indicate that generally infected rats developed cysticerci in the brain tissue after 4 months, and the cysticerci were observed in the parenchymal, ventricle, or submeningeal brain tissue. The route of infection did not have a statistically significant effect on the proportion of rats that developed cysticerci, and there was no dependence on infection dose. However, rat age was crucial to the success of the infection. Epilepsy was observed in 9% of rats with neurocysticercosis. In histologic examination, a layer of collagen tissue, inflammatory infiltrate cells, perivascular infiltrate, angiogenesis, spongy change, and mass effect were observed in the tissue surrounding the cysts. This study presents a suitable animal model for the study of human neurocysticercosis. PMID:26216286

  2. Novel rat model for neurocysticercosis using Taenia solium.

    PubMed

    Verastegui, Manuela R; Mejia, Alan; Clark, Taryn; Gavidia, Cesar M; Mamani, Javier; Ccopa, Fredy; Angulo, Noelia; Chile, Nancy; Carmen, Rogger; Medina, Roxana; García, Hector H; Rodriguez, Silvia; Ortega, Ynes; Gilman, Robert H

    2015-08-01

    Neurocysticercosis is caused by Taenia solium infecting the central nervous system and is the leading cause of acquired epilepsy and convulsive conditions worldwide. Research into the pathophysiology of the disease and appropriate treatment is hindered by lack of cost-effective and physiologically similar animal models. We generated a novel rat neurocysticercosis model using intracranial infection with activated T. solium oncospheres. Holtzman rats were infected in two separate groups: the first group was inoculated extraparenchymally and the second intraparenchymally, with different doses of activated oncospheres. The groups were evaluated at three different ages. Histologic examination of the tissue surrounding T. solium cysticerci was performed. Results indicate that generally infected rats developed cysticerci in the brain tissue after 4 months, and the cysticerci were observed in the parenchymal, ventricle, or submeningeal brain tissue. The route of infection did not have a statistically significant effect on the proportion of rats that developed cysticerci, and there was no dependence on infection dose. However, rat age was crucial to the success of the infection. Epilepsy was observed in 9% of rats with neurocysticercosis. In histologic examination, a layer of collagen tissue, inflammatory infiltrate cells, perivascular infiltrate, angiogenesis, spongy change, and mass effect were observed in the tissue surrounding the cysts. This study presents a suitable animal model for the study of human neurocysticercosis.

  3. Ciclamilast Ameliorates Adjuvant-Induced Arthritis in a Rat Model

    PubMed Central

    Zhang, Zhi-cheng; Zhang, Shui-juan; Jin, Bo; Wu, Yujin; Yang, Xin-fu; Yu, Bing; Xie, Qiang-min

    2015-01-01

    We assessed the effect of a novel and selective phosphodiesterase 4 (PDE4) inhibitor, ciclamilast, on chronic inflammation in adjuvant-induced arthritis (AIA), a rat model of rheumatoid arthritis (RA), and acute inflammation in the rat and mouse model of carrageenan-induced paw edema and peritonitis. Our results showed that daily oral administration of ciclamilast at 1, 3, and 10 mg/kg dose-dependently inhibited the increase in hind paw volume of rats with AIA. The inhibition of paw edema was associated with inhibition of both the production of cytokines such as TNF-α, IL-1β, and IL-6 and cell infiltration assessed in subcutaneous paw tissue. Moreover, there was significantly less tissue destruction in the ciclamilast-treated rats compared to the vehicle-treated rats, as assessed by radiographic analysis and histopathological evaluation. In the two acute inflammation models, ciclamilast inhibited carrageenan-induced paw edema in rats and inflammatory cell migration into the peritoneal cavity in mice in a dose-dependent manner. These results not only suggest that ciclamilast, as a disease-modifying antirheumatic drug (DMARD), can attenuate RA but also provide proof of principle that a PDE4 inhibitor may be useful for the treatment of arthritis. PMID:26000303

  4. Novel rat model for neurocysticercosis using Taenia solium.

    PubMed

    Verastegui, Manuela R; Mejia, Alan; Clark, Taryn; Gavidia, Cesar M; Mamani, Javier; Ccopa, Fredy; Angulo, Noelia; Chile, Nancy; Carmen, Rogger; Medina, Roxana; García, Hector H; Rodriguez, Silvia; Ortega, Ynes; Gilman, Robert H

    2015-08-01

    Neurocysticercosis is caused by Taenia solium infecting the central nervous system and is the leading cause of acquired epilepsy and convulsive conditions worldwide. Research into the pathophysiology of the disease and appropriate treatment is hindered by lack of cost-effective and physiologically similar animal models. We generated a novel rat neurocysticercosis model using intracranial infection with activated T. solium oncospheres. Holtzman rats were infected in two separate groups: the first group was inoculated extraparenchymally and the second intraparenchymally, with different doses of activated oncospheres. The groups were evaluated at three different ages. Histologic examination of the tissue surrounding T. solium cysticerci was performed. Results indicate that generally infected rats developed cysticerci in the brain tissue after 4 months, and the cysticerci were observed in the parenchymal, ventricle, or submeningeal brain tissue. The route of infection did not have a statistically significant effect on the proportion of rats that developed cysticerci, and there was no dependence on infection dose. However, rat age was crucial to the success of the infection. Epilepsy was observed in 9% of rats with neurocysticercosis. In histologic examination, a layer of collagen tissue, inflammatory infiltrate cells, perivascular infiltrate, angiogenesis, spongy change, and mass effect were observed in the tissue surrounding the cysts. This study presents a suitable animal model for the study of human neurocysticercosis. PMID:26216286

  5. Status of colitis-associated cancer in ulcerative colitis

    PubMed Central

    Kinugasa, Tetsushi; Akagi, Yoshito

    2016-01-01

    Surgical therapy for ulcerative colitis (UC) depends on the medical therapy administered for the patient’s condition. UC is a benign disease. However, it has been reported that the rare cases of cancer in UC patients are increasing, and such cases have a worse prognosis. Recently, surgical therapy has greatly changed, there has been quite an increase in the number of UC patients with high-grade dysplasia and/or cancer. These lesions are known as colitis-associated cancer (CAC). The relationship between inflammation and tumorigenesis is well-established, and in the last decade, a great deal of supporting evidence has been obtained from genetic, pharmacological, and epidemiological studies. Inflammatory bowel disease, especially UC, is an important risk factor for the development of colon cancer. We should determine the risk factors for UC patients with cancer based on a large body of data, and we should attempt to prevent the increase in the number of such patients using these newly identified risk factors in the near future. Actively introducing the surgical treatment in addition to medical treatment should be considered. Several physicians should analyze UC from their unique perspectives in order to establish new clinically relevant diagnostic and treatment methods in the future. This article discusses CAC, including its etiology, mechanism, diagnosis, and treatment in UC patients. PMID:27096030

  6. Intestinal Microbiota Signatures Associated with Inflammation History in Mice Experiencing Recurring Colitis

    PubMed Central

    Berry, David; Kuzyk, Orest; Rauch, Isabella; Heider, Susanne; Schwab, Clarissa; Hainzl, Eva; Decker, Thomas; Müller, Mathias; Strobl, Birgit; Schleper, Christa; Urich, Tim; Wagner, Michael; Kenner, Lukas; Loy, Alexander

    2015-01-01

    Acute colitis causes alterations in the intestinal microbiota, but the microbiota is thought to recover after such events. Extreme microbiota alterations are characteristic of human chronic inflammatory bowel diseases, although alterations reported in different studies are divergent and sometimes even contradictory. To better understand the impact of periodic disturbances on the intestinal microbiota and its compositional difference between acute and relapsing colitis, we investigated the beginnings of recurrent inflammation using the dextran sodium sulfate (DSS) mouse model of chemically induced colitis. Using bacterial 16S rRNA gene-targeted pyrosequencing as well as quantitative fluorescence in situ hybridization, we profiled the intestinal and stool microbiota of mice over the course of three rounds of DSS-induced colitis and recovery. We found that characteristic inflammation-associated microbiota could be detected in recovery-phase mice. Successive inflammation episodes further drove the microbiota into an increasingly altered composition post-inflammation, and signatures of colitis history were detectable in the microbiota more sensitively than by pathology analysis. Bacterial indicators of murine colitis history were identified in intestinal and stool samples, with a high degree of consistency between both sample types. Stool may therefore be a promising non-invasive source of bacterial biomarkers that are highly sensitive to inflammation state and history. PMID:26697002

  7. A novel rat model for chemotherapy-induced alopecia

    PubMed Central

    Wikramanayake, T. C.; Amini, S.; Simon, J.; Mauro, L. M.; Elgart, G.; Schachner, L. A.; Jimenez, J. J.

    2011-01-01

    Summary Background More than half of all people diagnosed with cancer receive chemotherapy, and approximately 65% of these develop chemotherapy-induced alopecia (CIA), a side-effect that can have considerable negative psychological repercussions. Currently, there are very few animal models available to study the mechanism and prevention of CIA. Aim To develop a clinically relevant adult rat model for CIA. Methods We first tested whether neonatal pigmented Long–Evans (LE) rats developed alopecia in response to the chemotherapeutic agents etoposide and cyclophosphamide. We then determined whether the rats developed CIA as adults. In the latter experiment, rat dorsal hair was clipped during the early telogen stage to synchronize the hair cycle. and starting 15 days later, the rats were treated with etoposide for 3 days. Results Neonatal LE pups developed CIA in response to etoposide and cyclophosphamide, similar to other murine models for CIA. Clipping of the hair shaft during early telogen resulted in synchronized anagen induction and subsequent alopecia after etoposide treatment in the clipped areas only. Hair follicles in the clipped areas had the typical chemotherapy-induced follicular dystrophy (dystrophic catagen). When the hair in the pigmented alopecic areas regrew, it had normal pigmentation. Conclusions A novel, pigmented adult rat model has been established for CIA. By hair shaft clipping during early telogen, synchronized anagen entry was induced that resulted in alopecia in response to chemotherapy. This is the first clinically relevant adult rat model for CIA and will be a useful tool to test agents for the prevention and treatment of CIA. PMID:22409523

  8. Increased GABAB receptor signaling in a rat model for schizophrenia

    PubMed Central

    Selten, Martijn M.; Meyer, Francisca; Ba, Wei; Vallès, Astrid; Maas, Dorien A.; Negwer, Moritz; Eijsink, Vivian D.; van Vugt, Ruben W. M.; van Hulten, Josephus A.; van Bakel, Nick H. M.; Roosen, Joey; van der Linden, Robert J.; Schubert, Dirk; Verheij, Michel M. M.; Kasri, Nael Nadif; Martens, Gerard J. M.

    2016-01-01

    Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20–22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats. While we did not observe changes in basal synaptic transmission onto LII/III pyramidal cells in the mPFC of APO-SUS compared to APO-UNSUS rats, we report reduced paired-pulse ratios at longer inter-stimulus intervals. The GABAB receptor antagonist CGP 55845 abolished this reduction, indicating that the decreased paired-pulse ratio was caused by increased GABAB signaling. Consistently, we find an increased expression of the GABAB1 receptor subunit in APO-SUS rats. Our data provide physiological evidence for increased presynaptic GABAB signaling in the mPFC of APO-SUS rats, further supporting an important role for the GABAergic system in the pathophysiology of schizophrenia. PMID:27687783

  9. Factors precipitating acute ulcerative colitis.

    PubMed

    Puri, A S; Chaubal, C C; Midha, Vandana

    2014-08-01

    Ulcerative colitis is characterized by mucosal inflammation of a variable length of the colon starting from the rectum. The precise etiopathogenesis is unknown but it occurs in genetically susceptible individuals who manifest an abnormal immunological response against gut commensal bacteria. The disease course is-characterized by multiple spontaneous relapses and remissions. Two pathogens namely CMV and C. difficile have been associated with disease exacerbation in specific clinical situations. Whereas C. difficile may produce worsening of the disease in those exposed to broad spectrum antibiotics, CMV reactivation is seen only in patients with moderate to severe steroid refractory disease. The importance of these two super-infections can be gauged by the fact that both the ACG and the ECCO recommend testing for these two pathogens in appropriate clinical situations. The applicability of these guidelines in the Indian scenario has yet to be determined in view of the bacterial and parasitic infections endemic in tropical countries. The guidelines for diagnosis and management of these two super-infections in the presence of ulcerative colitis are discussed in this review. PMID:25735121

  10. Detection of visual signals by rats: A computational model

    EPA Science Inventory

    We applied a neural network model of classical conditioning proposed by Schmajuk, Lam, and Gray (1996) to visual signal detection and discrimination tasks designed to assess sustained attention in rats (Bushnell, 1999). The model describes the animals’ expectation of receiving fo...

  11. Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability.

    PubMed

    Klicek, R; Kolenc, D; Suran, J; Drmic, D; Brcic, L; Aralica, G; Sever, M; Holjevac, J; Radic, B; Turudic, T; Kokot, A; Patrlj, L; Rucman, R; Seiwerth, S; Sikiric, P

    2013-10-01

    Stable gastric pentadecapeptide BPC 157 was suggested to link inflammatory bowel disease and multiple sclerosis, and thereby, shown to equally counteract the models of both of those diseases. For colitis, cysteamine (400 mg/kg intrarectally (1 ml/rat)) and colon-colon anastomosis (sacrifice at day 3, 5, 7, and 14) were used. BPC 157 (10 μg/kg, 10 ng/kg) was applied either intraperitoneally once time daily (first application immediately after surgery, last at 24 hours before sacrifice) or per-orally in drinking water (0.16 μg/ml/12 ml/day till the sacrifice) while controls simultaneously received an equivolume of saline (5 ml/kg) intraperitoneally or drinking water only (12 ml/day). A multiple sclerosis suited toxic rat model, cuprizone (compared with standard, a several times higher regimen, 2.5% of diet regimen + 1 g/kg intragastrically/day) was combined with BPC 157 (in drinking water 0.16 μg or 0.16 ng/ml/12 ml/day/rat + 10 μg or 10 ng/kg intragastrically/day) till the sacrifice at day 4. In general, the controls could not heal cysteamine colitis and colon-colon anastomosis. BPC 157 induced an efficient healing of both at the same time. Likewise, cuprizone-controls clearly exhibited an exaggerated and accelerated damaging process; nerve damage appeared in various brain areas, with most prominent damage in corpus callosum, laterodorsal thalamus, nucleus reunions, anterior horn motor neurons. BPC 157-cuprizone rats had consistently less nerve damage in all damaged areas, especially in those areas that otherwise were most affected. Consistently, BPC 157 counteracted cerebellar ataxia and impaired forelimb function. Thereby, this experimental evidence advocates BPC 157 in both inflammatory bowel disease and multiple sclerosis therapy. PMID:24304574

  12. Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability.

    PubMed

    Klicek, R; Kolenc, D; Suran, J; Drmic, D; Brcic, L; Aralica, G; Sever, M; Holjevac, J; Radic, B; Turudic, T; Kokot, A; Patrlj, L; Rucman, R; Seiwerth, S; Sikiric, P

    2013-10-01

    Stable gastric pentadecapeptide BPC 157 was suggested to link inflammatory bowel disease and multiple sclerosis, and thereby, shown to equally counteract the models of both of those diseases. For colitis, cysteamine (400 mg/kg intrarectally (1 ml/rat)) and colon-colon anastomosis (sacrifice at day 3, 5, 7, and 14) were used. BPC 157 (10 μg/kg, 10 ng/kg) was applied either intraperitoneally once time daily (first application immediately after surgery, last at 24 hours before sacrifice) or per-orally in drinking water (0.16 μg/ml/12 ml/day till the sacrifice) while controls simultaneously received an equivolume of saline (5 ml/kg) intraperitoneally or drinking water only (12 ml/day). A multiple sclerosis suited toxic rat model, cuprizone (compared with standard, a several times higher regimen, 2.5% of diet regimen + 1 g/kg intragastrically/day) was combined with BPC 157 (in drinking water 0.16 μg or 0.16 ng/ml/12 ml/day/rat + 10 μg or 10 ng/kg intragastrically/day) till the sacrifice at day 4. In general, the controls could not heal cysteamine colitis and colon-colon anastomosis. BPC 157 induced an efficient healing of both at the same time. Likewise, cuprizone-controls clearly exhibited an exaggerated and accelerated damaging process; nerve damage appeared in various brain areas, with most prominent damage in corpus callosum, laterodorsal thalamus, nucleus reunions, anterior horn motor neurons. BPC 157-cuprizone rats had consistently less nerve damage in all damaged areas, especially in those areas that otherwise were most affected. Consistently, BPC 157 counteracted cerebellar ataxia and impaired forelimb function. Thereby, this experimental evidence advocates BPC 157 in both inflammatory bowel disease and multiple sclerosis therapy.

  13. T regulatory cells and B cells cooperate to form a regulatory loop that maintains gut homeostasis and suppresses dextran sulfate sodium-induced colitis.

    PubMed

    Wang, L; Ray, A; Jiang, X; Wang, J-y; Basu, S; Liu, X; Qian, T; He, R; Dittel, B N; Chu, Y

    2015-11-01

    Regulatory T cells (Tregs) and B cells present in gut-associated lymphoid tissues (GALT) are both implicated in the resolution of colitis. However, how the functions of these cells are coordinated remains elusive. We used the dextran sulfate sodium (DSS)-induced colitis model combined with gene-modified mice to monitor the progression of colitis, and simultaneously examine the number of Tregs and B cells, and the production of IgA antibodies. We found that DSS-treated mice exhibited more severe colitis in the absence of B cells, and that the adoptive transfer of B cells attenuated the disease. Moreover, the transfer of IL-10(-/-) B cells also attenuated colitis, suggesting that B cells inhibited colitis through an interleukin-10 (IL-10)-independent pathway. Furthermore, antibody depletion of Tregs resulted in exacerbated colitis. Intriguingly, the number of GALT Tregs in B cell-deficient mice was significantly decreased during colitis and the adoptive transfer of B cells into these mice restored the Treg numbers, indicating that B cells contribute to Treg homeostasis. We also found that B cells induced the proliferation of Tregs that in turn promoted B-cell differentiation into IgA-producing plasma cells. These results demonstrate that B cells and Tregs interact and cooperate to prevent excessive immune responses that can lead to colitis.

  14. T regulatory cells and B cells cooperate to form a regulatory loop that maintains gut homeostasis and suppresses dextran sulfate sodium-induced colitis

    PubMed Central

    Wang, L; Ray, A; Jiang, X; Wang, J-y; Basu, S; Liu, X; Qian, T; He, R; Dittel, B N; Chu, Y

    2015-01-01

    Regulatory T cells (Tregs) and B cells present in gut-associated lymphoid tissues (GALT) are both implicated in the resolution of colitis. However, how the functions of these cells are coordinated remains elusive. We used the dextran sulfate sodium (DSS)-induced colitis model combined with gene-modified mice to monitor the progression of colitis, and simultaneously examine the number of Tregs and B cells, and the production of IgA antibodies. We found that DSS-treated mice exhibited more severe colitis in the absence of B cells, and that the adoptive transfer of B cells attenuated the disease. Moreover, the transfer of IL-10−/− B cells also attenuated colitis, suggesting that B cells inhibited colitis through an interleukin-10 (IL-10)-independent pathway. Furthermore, antibody depletion of Tregs resulted in exacerbated colitis. Intriguingly, the number of GALT Tregs in B cell-deficient mice was significantly decreased during colitis and the adoptive transfer of B cells into these mice restored the Treg numbers, indicating that B cells contribute to Treg homeostasis. We also found that B cells induced the proliferation of Tregs that in turn promoted B-cell differentiation into IgA-producing plasma cells. These results demonstrate that B cells and Tregs interact and cooperate to prevent excessive immune responses that can lead to colitis. PMID:25807185

  15. [Simultaneous occurrence of lymphocytic gastritis and lymphocytic colitis with transition to collagenous colitis].

    PubMed

    Christ, A D; Meier, R; Bauerfeind, P; Wegmann, W; Gyr, K

    1993-07-31

    Lymphocytic gastritis and lymphocytic colitis are two rare disorders of unknown etiology, only diagnosable by histology. Simultaneous occurrence of lymphocytic colitis and lymphocytic gastritis has not been described up to now. A 69-year-old female patient was examined because of crampy abdominal pain and watery diarrhea. Laboratory tests did not reveal an etiology and in colonoscopy the colon and terminal ileum were normal. Histology disclosed lymphocytic colitis. Esophagogastroduodenoscopy showed erosive bulbitis. Biopsies of the stomach revealed lymphocytic gastritis. A second colonoscopy one year later showed the development of collagenous colitis. PMID:8367708

  16. Moderate Exercise Training Attenuates the Severity of Experimental Rodent Colitis: The Importance of Crosstalk between Adipose Tissue and Skeletal Muscles

    PubMed Central

    Mazur-Bialy, Agnieszka I.; Krzysiek-Maczka, Gracjana; Urbanczyk, Katarzyna; Ptak-Belowska, Agata; Mach, Tomasz; Brzozowski, Tomasz

    2015-01-01

    Although progress has been recently made in understanding of inflammatory bowel diseases (IBD), their etiology is unknown apart from several factors from adipose tissue and skeletal muscles such as cytokines, adipokines, and myokines were implicated in the pathogenesis of ulcerative colitis. We studied the effect high-fat diet (HFD; cholesterol up to 70%), low-fat diet (LFD; cholesterol up to 10%), and the normal diet (total fat up to 5%) in rats with TNBS colitis forced to treadmill running exercise (5 days/week) for 6 weeks. In nonexercising HFD rats, the area of colonic damage, colonic tissue weight, the plasma IL-1β, TNF-α, TWEAK, and leptin levels, and the expression of IL-1β-, TNF-α-, and Hif1α mRNAs were significantly increased and a significant fall in plasma adiponectin and irisin levels was observed as compared to LFD rats. In HFD animals, the exercise significantly accelerated the healing of colitis, raised the plasma levels of IL-6 and irisin, downregulated the expression of IL-1β, TNF-α, and Hif1α, and significantly decreased the plasma IL-1β, TNF α, TWEAK, and leptin levels. We conclude that HFD delays the healing of colitis in trained rats via decrease in CBF and plasma IL-1β, TNF-α, TWEAK, and leptin levels and the release of protective irisin. PMID:25684862

  17. Physiologically based pharmacokinetic modeling of deltamethrin: Development of a rat and human diffusion-limited model

    EPA Science Inventory

    Mirfazaelian et al. (2006) developed a physiologically based pharmacokinetic (PBPK) model for the pyrethroid pesticide deltamethrin in the rat. This model describes gastrointestinal tract absorption as a saturable process mediated by phase III efflux transporters which pump delta...

  18. Histological evaluation in ulcerative colitis.

    PubMed

    DeRoche, Tom C; Xiao, Shu-Yuan; Liu, Xiuli

    2014-08-01

    This review summarizes diagnostic problems, challenges and advances in ulcerative colitis (UC). It emphasizes that, although histopathological examination plays a major role in the diagnosis and management of UC, it should always be interpreted in the context of clinical, endoscopic, and radiological findings. Accurate diagnosis requires knowledge of the classic morphological features of UC, as well as a number of atypical pathological presentations that may cause mis-classification of the disease process, either in resection or biopsy specimens. These atypical pathological presentations include rectal sparing and patchiness of disease at initial presentation of UC in pediatric patients or in the setting of medically treated UC, cecal or ascending colon inflammation in left-sided UC, and backwash ileitis in patients with severe ulcerative pancolitis. Loosely formed microgranulomas, with pale foamy histiocytes adjacent to a damaged crypt or eroded surface, should not be interpreted as evidence of Crohn's disease. Indeterminate colitis should only be used in colectomy specimens as a provisional pathological diagnosis. Patients with UC are at risk for the development of dysplasia and carcinoma; optimal outcomes in UC surveillance programs require familiarity with the diagnostic criteria and challenges relating to UC-associated dysplasia and malignancy. Colon biopsy from UC patients should always be evaluated for dysplasia based on cytological and architectural abnormalities. Accurate interpretation and classification of dysplasia in colon biopsy from UC patients as sporadic adenoma or UC-related dysplasia [flat, adenoma-like, or dysplasia-associated lesion or mass (DALM)] requires clinical and endoscopic correlation. Isolated polypoid dysplastic lesions are considered to be sporadic adenoma if occurring outside areas of histologically proven colitis, or adenoma-like dysplasia if occurring in the diseased segment. Recent data suggest that such lesions may be treated

  19. Diagnosis and treatment of microscopic colitis.

    PubMed

    Okamoto, Ryuichi; Negi, Mariko; Tomii, Syohei; Eishi, Yoshinobu; Watanabe, Mamoru

    2016-08-01

    Microscopic colitis (MC) designates two types of chronic diarrhea diseases, which are lymphocytic colitis and collagenous colitis. The prevalence of microscopic colitis is increasing in both Western and Eastern countries, possibly due to the high incidence of colonoscopic survey in chronic diarrhea patients. Although the overall prognosis of MC patients is mostly good, it should be noted that appropriate diagnosis and choice of treatment is required to assure a good clinical outcome for MC patients. Also, a certain population of MC patients may take a severe and refractory clinical course, and thus require advanced clinical care using medications supported by less evidence. In this review, we would like to feature the essential points regarding the diagnosis of MC, and also describe the current standard of treatments for MC patients. In addition, we would like to add some findings from the national survey and research carried out in Japan, to compare those data with the western countries. PMID:27271790

  20. Opposing roles of Prostaglandin D2 receptors in ulcerative colitis

    PubMed Central

    Sturm, Eva M.; Radnai, Balazs; Jandl, Katharina; Stančić, Angela; Parzmair, Gerald P.; Högenauer, Christoph; Kump, Patrizia; Wenzl, Heimo; Petritsch, Wolfgang; Pieber, Thomas R.; Schuligoi, Rufina; Marsche, Gunther; Ferreirós, Nerea; Heinemann, Akos; Schicho, Rudolf

    2014-01-01

    Pro-resolution functions were reported for Prostaglandin D2 (PGD2) in colitis, but the role of its two receptors, DP and in particular CRTH2 are less well defined. We investigated DP and CRTH2 expression and function during human and murine ulcerative colitis (UC). Expression of receptors was measured by flow cytometry on peripheral blood leukocytes, and by immunohistochemistry and immunoblotting in colon biopsies of patients with active UC and healthy individuals. Receptor involvement in UC was evaluated in a mouse model of DSS colitis. DP and CRTH2 expression changed in leukocytes of patients with active UC in a differential manner. In UC patients, DP showed higher expression in neutrophils but lower in monocytes as compared to control subjects. In contrast, CRTH2 was decreased in eosinophils, NK and CD3+ T cells but not in monocytes and CD3+/CD4+ T cells. The decrease of CRTH2 on blood eosinophils clearly correlated with disease activity. DP correlated positively with disease activity in eosinophils but inversely in neutrophils. CRTH2 internalized upon treatment with PGD2 and 11-dehydroTXB2 in eosinophils of controls. Biopsies of UC patients revealed an increase of CRTH2-positive cells in the colonic mucosa and high CRTH2 protein content. The CRTH2 antagonist CAY10595 improved while the DP antagonist MK0524 worsened inflammation in murine colitis. DP and CRTH2 play differential roles in UC. Although expression of CRTH2 on blood leukocytes is downregulated in UC, CRTH2 is present in colon tissue where it may contribute to inflammation whereas DP likely promotes anti-inflammatory actions. PMID:24929001

  1. RORγt(+) hematopoietic cells are necessary for tumor cell proliferation during colitis-associated tumorigenesis in mice.

    PubMed

    Martin, Maria; Kesselring, Rebecca K; Saidou, Balam; Brunner, Stefan M; Schiechl, Gabriela; Mouris, Verena F; Wege, Anja K; Rümmele, Petra; Schlitt, Hans J; Geissler, Edward K; Fichtner-Feigl, Stefan

    2015-06-01

    Colorectal cancer (CRC) is one of the most common tumor entities. In patients with inflammatory bowel diseases, the development of colitis-associated colon cancer is considered a dangerous long-term complication. IL-17A and the transcription factor retinoic acid receptor-related orphan receptor γt (RORγt) play fundamental roles in the pathogenesis of inflammatory bowel diseases; in human studies, we detected a dense infiltration of RORγt-dependent CD4(+) IL17A(+) T helper (Th)17 cells in specimens of CRC, ulcerative colitis, and ulcerative colitis-associated colorectal cancer. However, the mechanistic role of RORγt(+) hematopoietic cells in colitis-associated tumorigenesis remains unclear. To investigate colitis-associated colon tumorigenesis, we conducted studies in the AOM+DSS mouse model that revealed the importance of RORγt for colon tumor progression. In the absence of RORγt-dependent Th17 lymphocytes, mice showed signs of intense chronic colitis, but developed significantly fewer macroscopic tumor nodules. The reduction of tumor development in RORγt(-/-) mice was not due to reduced colon tumor initiation. However, the proliferation rate of tumor cells was reduced in the absence of RORγt-dependent Th17 cells and tumor cells showed pronounced signs of senescence-associated epigenetic and lysosomal changes. These results indicate an important role for the immunological milieu in colitis-associated cancer, which is shaped in-part by RORγt-dependent Th17 lymphocytes that support CRC growth.

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

    SciTech Connect

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

    2009-05-15

    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.

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

    PubMed

    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.

  4. Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

    PubMed Central

    Di Giovangiulio, Martina; Bosmans, Goele; Meroni, Elisa; Stakenborg, Nathalie; Florens, Morgane; Farro, Giovanna; Gomez-Pinilla, Pedro J; Matteoli, Gianluca; Boeckxstaens, Guy E

    2016-01-01

    Vagotomy (VGX) increases the susceptibility to develop colitis suggesting a crucial role for the cholinergic anti-inflammatory pathway in the regulation of the immune responses. Since oral tolerance and the generation of regulatory T cells (Tregs) are crucial to preserve mucosal immune homeostasis, we studied the effect of vagotomy and the involvement of α7 nicotinic receptors (α7nAChR) at the steady state and during colitis. Therefore, the development of both oral tolerance and colitis (induced by dextran sulfate sodium (DSS) or via T cell transfer) was studied in vagotomized mice and in α7nAChR-/- mice. VGX, but not α7nAChR deficiency, prevented oral tolerance establishment. This effect was associated with reduced Treg conversion in the lamina propria and mesenteric lymphnodes. To the same extent, vagotomized mice, but not α7nAChR-/- mice, developed a more severe DSS colitis compared with control mice treated with DSS, associated with a decreased number of colonic Tregs. However, neither VGX nor absence of α7nAChR in recipient mice affected colitis development in the T cell transfer model. In line, deficiency of α7nAChR exclusively in T cells did not influence the development of colitis induced by T cell transfer. Our results indicate a key role for the vagal intestinal innervation in the development of oral tolerance and colitis, most likely by modulating induction of Tregs independently of α7nAChR. PMID:27341335

  5. Protective Effect of Laminaria japonica with Probiotics on Murine Colitis

    PubMed Central

    Bu, Youngmin; Bae, Jinhyun; Bang, Yu-mi; Kim, Jinsung; Lee, Hyejung; Beom-Joon, Lee; Hyun, Yoo Hye

    2014-01-01

    Inflammatory bowel disease (IBD) is a chronically relapsing inflammatory disorder of the gastrointestinal tract. Most IBD treatments are unsatisfactory; therefore, various dietary supplements have emerged as promising interventions. Laminaria japonica (LJ) is an edible seaweed used to regulate digestive symptoms. Probiotics have been reported to improve digestive problems and their simultaneous administration with seaweeds has been shown to produce synergistic therapeutic effects. Here, we investigated the effect of LJ combination with probiotics on dextran sodium sulfate-induced colitis model in mice. Aqueous LJ extracts (LJE) at doses from 100 to 300 mg/kg and probiotics at a dose of 300 mg/kg were orally administered for 7 days. Body weight, colon length, histological score, macroscopic damage, and the levels of cytokines IFN-γ, IL-1β, IL-6, IL-10, IL-12 (P40), IL-12 (P70), IL-17, and TNF-α were assessed. LJE alone caused a significant improvement of colitis signs such as colon length, histological score, and IL-1β and IL-6 production. LJE and probiotics demonstrated a synergistic effect by the histological score and levels of IL-1β, IL-6, and IL-12 (P40) but not IFN-γ, IL-10, and IL-12 (P70). In conclusion, LJE was effective in inducing protection against colitis in mice and acted synergistically with probiotics. PMID:24948848

  6. Pathophysiology of unilateral pulmonary aspergillosis in an experimental rat model.

    PubMed

    Becker, Martin J; De Marie, Siem; Fens, Marcel H A M; Haitsma, Jack J; Verbrugh, Henri A; Lachmann, Burkhard; Bakker-Woudenberg, Irma A J M

    2006-03-01

    Because little is known about the pathophysiology of invasive pulmonary aspergillosis (IPA), we examined changes in pulmonary and general physiology during this disease in an animal model. In a model of fatal left-sided IPA, 19 persistently neutropenic rats were monitored for clinical signs including body temperature, body weight and respiratory distress. A separate group of nine rats with IPA was used for measurements of arterial blood pressure, arterial O2 and CO2 pressure, lung compliance and surfactant function. Body temperature and body weight decreased, whereas respiratory distress increased during progression of the disease. Compared to uninfected controls, in rats with IPA arterial blood pressure and lung compliance were significantly lower, and left lung minimal surface tension was significantly higher. Right lung surfactant function was not affected. Arterial O2 and CO2 pressures were not different between rats with IPA and uninfected controls. Infection with Aspergillus fumigatus in neutropenic rats resulted in hypothermia, body weight loss and respiratory distress. Loss of left lung function was probably compensated by the uninfected right lung, even in a late stage of the disease. Circulatory failure was a major feature in the terminal phase of the infection. PMID:16519016

  7. Bacterial translocation in the rat model of lectin induced diarrhoea.

    PubMed

    Shoda, R; Mahalanabis, D; Wahed, M A; Albert, M J

    1995-03-01

    Red kidney beans were fed to weanling Long-Evans rats to cause diarrhoea (mean (SD) faecal wet weight: 2.66 (0.73) g/day in six rats fed beans v 1.12 (0.47) g/day in six control rats, p < 0.01) and increased faecal energy loss (4.87 (0.41) v 2.14 (0.23) kcal/day, p < 0.01). In addition, the rats fed beans had heavier small intestines (80.6 (4.6) v 51.9 (8.4) g/kg body weight, p < 0.01), heavier mesenteric lymph nodes (0.72 (0.27) v 0.08 (0.08) g/kg body weight, p < 0.05), and translocation of indigenous intestinal bacteria, Citrobacter Spp and Escherichia coli, to the mesenteric lymph nodes. (Translocation positive, that is, > 100 colonies per g of nodal tissue: 75% v 0%, p < 0.005.) These data suggest that diarrhoea induced by red kidney beans is a suitable model for studies of an important cause of persistent diarrhoea--that is, systemic complications. This rat model of lectin induced diarrhoea with translocation of intraluminal enteric bacteria into mesenteric lymph nodes should be useful in understanding the well known septicaemic complications associated with prolonged diarrhoea in infants and small children and in studies on factors that may modify or prevent bacterial translocation. PMID:7698696

  8. The economics of adalimumab for ulcerative colitis.

    PubMed

    Xie, Feng

    2015-06-01

    Ulcerative colitis is a chronic inflammatory disease, characterized by diffuse mucosal inflammation in the colon. Adalimumab, as a TNF-α blocker, offers a safe and efficacious treatment option for patients with moderate to severe ulcerative colitis and refractory or intolerant to conventional medications; however, its cost-effectiveness profile has not yet been well established. Future economic evaluations should choose appropriate comparators in the context of target-reimbursement decision making and focus on cost-effectiveness over a long time horizon.

  9. Intestinal microbiota and ulcerative colitis.

    PubMed

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota.

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

    PubMed Central

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

    2014-01-01

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

  11. Collagenous colitis: new diagnostic possibilities with endomicroscopy

    NASA Astrophysics Data System (ADS)

    Hoffman, A.; Goetz, M.; Biesterfeld, S.; Galle, P. R.; Neurath, M. F.; Kiesslich, R.

    2006-02-01

    Collagenous colitis is a kind of microscopic colitis. It is characterized by chronic watery diarrhea and abdominal pain. The etiology is still unknown. So far, for the diagnose a histological evaluation was necessary with the presence of thickened subepithelial collagneous bands in the lamina propria. A new developed endoscope with a confocal laser allows analysing cellular and subcellular details of the mucosal layer at high resolution in vivo. In this case report we describe for the first time to diagnose collagenous colitis during ongoing colonoscopy by using this confocal endomicroscopy. In a 67 year old female patient with typical symptoms the characteristic histological changes could be identified in the endomicroscopic view. Biopsies could be targeted to affected areas and endomicroscopic prediction of the presence of collagenous bands could be confirmed in all targeted biopsies. First endomicroscopic experience in microscopic colitis could be confirmed in four additional patients. Future prospective studies are warranted to further evaluate these initial findings. However, collagenous colitis is frequently missed and endomicroscopy seems to be the ideal tool for accurate diagnosing collagenous colitis during ongoing endoscopy.

  12. Colitis

    MedlinePlus

    ... Elsevier Saunders; 2016:chap 116. Wald A. Other diseases of the colon and rectum. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease . 10th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ...

  13. PHARMACOKINETIC/PHARMACODYNAMIC MODELING OF PERMETHRIN IN THE RAT

    EPA Science Inventory

    A physiologically-based pharmacokinetic (PBPK) model was used to describe pharmacokinetics of permethrin and calibrated using experimental data on the concentration time-course of cis- and trans-permethrin in rat blood and brain tissues following oral administration...

  14. Calcium Balance in A Rat Space Flight Model

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Navidi, M.; Holton, Emily M. (Technical Monitor)

    1997-01-01

    One of the main characteristics of calcium (Ca) metabolism during space flight and the human bed rest model for microgravity is negative Ca balance, attributed, to an increase in urinary Ca excretion and depressed intestinal Ca absorption. No differences or less positive Ca balances are reported after skeletal unloading in similar studies in weaning or juvenile rats. To determine Ca balances and evaluate the Ca endocrine system in mature rats exposed to a space flight model which unloaded the hind limbs by tail suspension, we modified the cage to quantify dietary, fecal and urinary Ca. Five 2-5 d balance periods in 8 loaded (C) and 8 unloaded (S) rats were compared during a 4 week study in 6 month old 490 g male rats. The first period revealed negative balances of -16+/-3 and -14+/-5 mg/d which reflected adaptation to the cages, the change in diet from Purina to AIN 76 and weight loss in both C and S. Average Ca balances in rats fed 0.1% Ca and 0.3% phosphorus (Pi) diets, remained negative in S and were less than C after 6 -10 d (-2.9 vs 0.12 mg/d, p<.05) but not thereafter. In spite of eating 10% more food than C, initial weight loss, restored in C, was never recovered in S. Fecal excretion exceeded dietary intake by -3.7% in S and reflected absorption and retention of 8.4% dietary Ca in C. Urinary Ca was the same fraction of dietary intake in S and C (9.0 vs 8.6%, NS). Serum Ca, Pi, parathyroid hormone and 1,25-dihydroxyvitamin D were the same in both groups after 28 days. In contrast to the human, a major determinant of negative Ca balance in the mature rat exposed to a space flight model appears to be losses from gastrointestinal Ca secretion, rather than urinary Ca excretion.

  15. Cytomegalovirus colitis followed by ischemic colitis in a non-immunocompromised adult: a case report.

    PubMed

    Hasegawa, Tsuyoshi; Aomatsu, Kazuki; Nakamura, Masanori; Aomatsu, Naoki; Aomatsu, Keiho

    2015-03-28

    We report a rare case of cytomegalovirus (CMV) colitis followed by severe ischemic colitis in a non-immunocompromised patient. An 86-year-old woman was admitted after experiencing episodes of vomiting and diarrhea. The next day, hematochezia was detected without abdominal pain. The initial diagnosis of ischemic colitis was based on colonoscopy and histological findings. The follow-up colonoscopy revealed a prolonged colitis. Immunohistochemical staining detected CMV-positive cells following conservative therapy. Intravenous ganciclovir therapy led to successful healing of ulcers and disappearance of CMV-positive cells. The prevalence of CMV infection is common in adults. CMV colitis is relatively common in immunocompromised patients; however, it is rare in immunocompetent patients. In our case, CMV infection was allowed to be established due to the disruption of the colonic mucosa by the prior severe ischemic colitis. Our experience suggests that biopsies may be necessary to detect CMV and the prompt management of CMV colitis should be instituted when intractable ischemic colitis is observed.

  16. Oral delivery of Bifidobacterium longum expressing α-melanocyte-stimulating hormone to combat ulcerative colitis.

    PubMed

    Wei, Pijin; Yang, Yan; Ding, Qing; Li, Xiuying; Sun, Hanxiao; Liu, Zhaobing; Huang, Junli; Gong, Yahui

    2016-02-01

    α-Melanocyte-stimulating hormone (α-MSH) is a tridecapeptide derived from pro-opiomelanocortin that exhibits potent anti-inflammatory properties by regulating the production of inflammatory mediators. This peptide has been well established in several inflammatory models, including inflammatory bowel disease (IBD). However, its extremely short duration in vivo limits its clinical application. To address this limitation, Bifidobacterium was used here as a carrier to deliver α-MSH. We utilized α-MSH-engineered Bifidobacterium against IBD, which is closely linked to immune and intestinal microbiota dysfunction. First, we constructed a Bifidobacterium longum secreting α-MSH (B. longum-α-MSH). We then tested the recombinant α-MSH expression and determined its bioactivity in HT-29 cells. To assess its effectiveness, B. longum-α-MSH was used against an ulcerative colitis (UC) model in rats induced by dextran sulfate sodium. The data showed that α-MSH expression in B. longum-α-MSH was effective, and its biological activity was similar to the synthesized one. This UC model experiment indicated that B. longum-α-MSH successfully colonized the intestinal gut, expressed bioactive α-MSH and had a significant anti-inflammatory effect. The results demonstrate the feasibility of preventing IBD by using B. longum-α-MSH. PMID:26567174

  17. The mathematical whisker: A review of numerical models of the rat׳s vibrissa biomechanics.

    PubMed

    Lucianna, Facundo Adrián; Albarracín, Ana Lía; Vrech, Sonia Mariel; Farfán, Fernando Daniel; Felice, Carmelo José

    2016-07-01

    The vibrissal system of the rat refers to specialized hairs the animal uses for tactile sensory perception. Rats actively move their whiskers in a characteristic way called "whisking". Interaction with the environment produces elastic deformation of the whiskers, generating mechanical signals in the whisker-follicle complex. Advances in our understanding of the vibrissal complex biomechanics is of interest not only for the biological research field, but also for biomimetic approaches. The recent development of whisker numerical models has contributed to comprehending its sophisticated movements and its interactions with the follicle. The great diversity of behavioral patterns and complexities of the whisker-follicle ensemble encouraged the creation of many different biomechanical models. This review analyzes most of the whisker biomechanical models that have been developed so far. This review was written so as to render it accessible to readers coming from different research areas.

  18. Preventive and Therapeutic Euphol Treatment Attenuates Experimental Colitis in Mice

    PubMed Central

    Bento, Allisson F.; Marcon, Rodrigo; Schmidt, Éder C.; Bouzon, Zenilda L.; Pianowski, Luiz F.; Calixto, João B.

    2011-01-01

    Background The tetracyclic triterpene euphol is the main constituent found in the sap of Euphorbia tirucalli. This plant is widely known in Brazilian traditional medicine for its use in the treatment of several kinds of cancer, including leukaemia, prostate and breast cancers. Here, we investigated the effect of euphol on experimental models of colitis and the underlying mechanisms involved in its action. Methodology/Principal Findings Colitis was induced in mice either with dextran sulfate sodium (DSS) or with 2,4,6-trinitrobenzene sulfonic acid (TNBS), and the effect of euphol (3, 10 and 30 mg/kg) on colonic injury was assessed. Pro-inflammatory mediators and cytokines were measured by immunohistochemistry, enzyme-Linked immunoabsorbent assay (ELISA), real time-polymerase chain reaction (RT-PCR) and flow cytometry. Preventive and therapeutic oral administration of euphol attenuated both DSS- and TNBS-induced acute colitis as observed by a significant reduction of the disease activity index (DAI), histological/microscopic damage score and myeloperoxidase (MPO) activity in colonic tissue. Likewise, euphol treatment also inhibited colon tissue levels and expression of IL-1β, CXCL1/KC, MCP-1, MIP-2, TNF-α and IL-6, while reducing NOS2, VEGF and Ki67 expression in colonic tissue. This action seems to be likely associated with inhibition of activation of nuclear factor-κB (NF-κB). In addition, euphol decreased LPS-induced MCP-1, TNF-α, IL-6 and IFN-γ, but increased IL-10 secretion from bone marrow-derived macrophages in vitro. Of note, euphol, at the same schedule of treatment, markedly inhibited both selectin (P- and E-selectin) and integrin (ICAM-1, VCAM-1 and LFA-1) expression in colonic tissue. Conclusions/Significance Together, these results clearly demonstrated that orally-administered euphol, both preventive or therapeutic treatment were effective in reducing the severity of colitis in two models of chemically-induced mouse colitis and suggest this plant

  19. Recombinant human MFG-E8 ameliorates colon damage in DSS- and TNBS-induced colitis in mice.

    PubMed

    Zhang, Yinzhong; Brenner, Max; Yang, Weng-Lang; Wang, Ping

    2015-05-01

    Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the digestive system and typically requires lifelong medical care. Recombinant human MFG-E8 (rhMFG-E8) is a 364-amino acid protein, which promotes apoptotic cell clearance and reduces inflammation. This study investigates the therapeutic effect of rhMFG-E8 on two well-established mouse models of IBD. Acute mucosal injury leading to colitis was caused by exposing C57BL/6 mice to 4% dextran sodium sulfate (DSS) in the drinking water over 7 days, and BALB/c mice to a single intrarectal dose of 2.75 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Upon clinical onset of colitis (day 2 in the DSS model and day 1 in the TNBS model), mice were treated with daily subcutaneous injections of rhMFG-E8 (60 or 120 μg/kg/day) or vehicle (saline) for 6 days. Treatment with rhMFG-E8 significantly attenuated colitis in both models in a dose-dependent way. Treatment of DSS-induced colitis with rhMFG-E8 (120 μg/kg/day) decreased weight loss by 59%, the colitis severity score by 71%, and colon shrinkage by 49% when compared with vehicle. Similarly, treatment of TNBS-induced colitis with rhMFG-E8 (120 μg/kg/day) decreased weight loss by 97%, the colitis severity score by 82%, and colon shrinkage by 62% when compared with vehicle. In both models, the colons of animals receiving rhMFG-E8 showed marked reduction in neutrophil infiltration, cytokine and chemokine expression, and apoptotic cell counts. In conclusion, rhMFG-E8 ameliorates DSS- and TNBS-induced colitis, suggesting that it has the potential to become a novel therapeutic agent for IBD.

  20. Sequestering HMGB1 via DNA-conjugated beads ameliorates murine colitis.

    PubMed

    Ju, Zhongliang; Chavan, Sangeeta S; 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.

  1. Neurobehavioral tests in rat models of degenerative brain diseases.

    PubMed

    Urbach, Yvonne K; Bode, Felix J; Nguyen, Huu Phuc; Riess, Olaf; von Hörsten, Stephan

    2010-01-01

    Each translational approach in medical research forces the establishment of neurobehavioral screening systems, dedicated to fill the gap between postgenomic generation of state-of-the-art animal models (i.e. transgenic rats) on the one hand and their added value for really predictive experimental preclinical therapy on the other. Owing to these developments in the field, neuroscientists are frequently challenged by the task of detecting discrete behavioral differences in rats. Systematic, comprehensive phenotyping covers these needs and represents a central part of the process. In this chapter, we provide an overview on theoretical issues related to comprehensive neurobehavioral phenotyping of rats and propose specific classical procedures, protocols (similar to the SHIRPA approach in mice), as well as techniques for repeated, intraindividual phenotyping. Neurological testing of rats, motorfunctional screening using the accelerod approach, emotional screening using the social interaction test of anxiety, and testing of sensorimotoric gating functions by prepulse inhibition of the startle response are provided in more detail. This description is completed by an outlook on most recent developments in the field dealing with automated, intra-home-cage technologies, allowing continuous screening in rats in various behavioral and physiological dimensions on an ethological basis.

  2. Inflammatory bowel disease in rats: Bacterial and chemical interaction

    PubMed Central

    Hussein, Inaya Abdallah Hajj; Tohme, Rania; Barada, Kassem; Mostafa, Mostafa Hassan; Freund, Jean-Noel; Jurjus, Rosalyn A; Karam, Walid; Jurjus, Abdo

    2008-01-01

    AIM: To develop a novel model of colitis in rats, using a combination of iodoacetamide and enteropathogenic E. coli (EPEC), and to elucidate the pathophysiologic processes implicated in the development of ulcerative colitis (UC). METHODS: Male Sprague-Dawley rats (n = 158) were inoculated intrarectally on a weekly basis with 4 different combinations: (a) 1% methylcellulose (MC), (b) 100 μL of 6% iodoacetamide (IA) in 1% MC, (c) 200 μL containing 4 × 108 colony factor units (CFU) of EPEC, and (d) combined treatment of (IA) followed by bacteria (B) after 2 d. Thirty days post treatment, each of the four groups was divided into two subgroups; the inoculation was stopped for one subgroup and the other subgroup continued with biweekly inoculation until the end of the experiment. Colitis was evaluated by the clinical course of the disease, the macroscopic and microscopic alterations, activity of myeloperoxidase (MPO), and by TNF-α gene expression. RESULTS: Findings indicative of UC were seen in the combined treatment (IA + B) as well as the IA continued treatment groups: the animals showed slow rate of increase in body weight, diarrhea, bloody stools, high colonic ulcer score, as well as histological alterations characteristic of UC, with an extensive inflammatory reaction. During the course of the experiment, the MPO activity was consistently elevated and the TNF-α gene expression was upregulated compared to the control animals. CONCLUSION: The experimental ulcerative colitis model used in the present study resembles, to a great extent, the human disease. It is reproducible with characteristics indicative of chronicity. PMID:18609687

  3. Melatonin improves experimental colitis with sleep deprivation

    PubMed Central

    PARK, YOUNG-SOOK; CHUNG, SOOK-HEE; LEE, SEONG-KYU; KIM, JA-HYUN; KIM, JUN-BONG; KIM, TAE-KYUN; KIM, DONG-SHIN; BAIK, HAING-WOON

    2015-01-01

    Sleep deprivation (SD) is an epidemic phenomenon in modern countries, and its harmful effects are well known. SD acts as an aggravating factor in inflammatory bowel disease. Melatonin is a sleep-related neurohormone, also known to have antioxidant and anti-inflammatory effects in the gastrointestinal tract; however, the effects of melatonin on colitis have been poorly characterized. Thus, in this study, we assessed the measurable effects of SD on experimental colitis and the protective effects of melatonin. For this purpose, male imprinting control region (ICR) mice (n=24) were used; the mice were divided into 4 experimental groups as follows: the control, colitis, colitis with SD and colitis with SD and melatonin groups. Colitis was induced by the administration of 5% dextran sulfate sodium (DSS) in the drinking water for 6 days. The mice were sleep-deprived for 3 days. Changes in body weight, histological analyses of colon tissues and the expression levels of pro-inflammatory cytokines and genes were evaluated. SD aggravated inflammation and these effects were reversed by melatonin in the mice with colitis. In addition, weight loss in the mice with colitis with SD was significantly reduced by the injection of melatonin. Treatment with melatonin led to high survival rates in the mice, in spite of colitis with SD. The levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-17, interferon-γ and tumor necrosis factor-α, in the serum of mice were significantly increased by SD and reduced by melatonin treatment. The melatonin-treated group showed a histological improvement of inflammation. Upon gene analysis, the expression of the inflammatory genes, protein kinase Cζ (PKCζ) and calmodulin 3 (CALM3), was increased by SD, and the levels decreased following treatment with melatonin. The expression levels of the apoptosis-related inducible nitric oxide synthase (iNOS) and wingless-type MMTV integration site family, member 5A (Wnt5a) genes was

  4. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

    PubMed Central

    Kuijk, Ewart W.; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M.; Cuppen, Edwin

    2016-01-01

    The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

  5. Comparison of starvation and elastase models of emphysema in the rat

    SciTech Connect

    Harkema, J.R.; Mauderly, J.L.; Gregory, R.E.; Pickrell, J.A.

    1984-01-01

    Starvation and elastase-induced changes in rat lung structure, biochemistry, and function were compared as models of human pulmonary emphysema. Ten-week-old male rats were instilled intratracheally with either porcine pancreatic elastase in saline (E) or with saline alone. A group of the saline-instilled rats were fed one third of their normal food intake until a 45% loss of body weight occurred (S). The remaining saline-instilled rats served as control animals (C). Post-treatment evaluations included in vivo respiratory function, lung histopathologic and morphometric analyses, lung tissue proteinolytic activity, and lung collagen. The E rats had in vivo respiratory function changes more similar to human emphysema than those of S rats. All lung volume subdivisions were decreased in S rats and increased in E rats. The volume-pressure curve of S rats was shifted to the right of the C curve, whereas that of E rats was shifted to the left. Forced expiratory flow rates of E rats were decreased at all lung volumes, but those of S rats were not. Both E and S rats had larger terminal air spaces and less alveolar surface area than did C rats. The S rats had more collagen per gram lung and higher proteinolytic activity than did C or E rats. These results show that, although starvation induces some changes characteristic of human emphysema, elastase-treatment provides a model more similar to the human disease. 44 references, 5 figures, 4 tables.

  6. Experimental model of heterotopic ossification in Wistar rats

    PubMed Central

    Zotz, T.G.G.; de Paula, J.B.; Moser, A.D.L.

    2012-01-01

    Heterotopic ossification (HO) is a metaplastic biological process in which there is newly formed bone in soft tissues adjacent to large joints, resulting in joint mobility deficit. In order to determine which treatment techniques are more appropriate for such condition, experimental models of induced heterotopic bone formation have been proposed using heterologous demineralized bone matrix implants and bone morphogenetic protein and other tissues. The objective of the present experimental study was to identify a reliable protocol to induce HO in Wistar rats, based on autologous bone marrow (BM) implantation, comparing 3 different BM volumes and based on literature evidence of this HO induction model in larger laboratory animals. Twelve male Wistar albino rats weighing 350/390 g were used. The animals were anesthetized for blood sampling before HO induction in order to quantify serum alkaline phosphatase (ALP). HO was induced by BM implantation in both quadriceps muscles of these animals, experimental group (EG). Thirty-five days after the induction, another blood sample was collected for ALP determination. The results showed a weight gain in the EG and no significant difference in ALP levels when comparing the periods before and after induction. Qualitative histological analysis confirmed the occurrence of heterotopic ossification in all 12 EG rats. In conclusion, the HO induction model was effective when 0.35 mL autologous BM was applied to the quadriceps of Wistar rats. PMID:22473322

  7. Acoustic noise improves motor learning in spontaneously hypertensive rats, a rat model of attention deficit hyperactivity disorder.

    PubMed

    Söderlund, Göran B W; Eckernäs, Daniel; Holmblad, Olof; Bergquist, Filip

    2015-03-01

    The spontaneously hypertensive (SH) rat model of ADHD displays impaired motor learning. We used this characteristic to study if the recently described acoustic noise benefit in learning in children with ADHD is also observed in the SH rat model. SH rats and a Wistar control strain were trained in skilled reach and rotarod running under either ambient noise or in 75 dBA white noise. In other animals the effect of methylphenidate (MPH) on motor learning was assessed with the same paradigms. To determine if acoustic noise influenced spontaneous motor activity, the effect of acoustic noise was also determined in the open field activity paradigm. We confirm impaired motor learning in the SH rat compared to Wistar SCA controls. Acoustic noise restored motor learning in SH rats learning the Montoya reach test and the rotarod test, but had no influence on learning in Wistar rats. Noise had no effect on open field activity in SH rats, but increased corner time in Wistar. MPH completely restored rotarod learning and performance but did not improve skilled reach in the SH rat. It is suggested that the acoustic noise benefit previously reported in children with ADHD is shared by the SH rat model of ADHD, and the effect is in the same range as that of stimulant treatment. Acoustic noise may be useful as a non-pharmacological alternative to stimulant medication in the treatment of ADHD.

  8. Emphysema model in rats treated intratracheally with elastase

    SciTech Connect

    Yokoyama, E.; Nambu, Z.; Uchiyama, I.; Kyono, H.

    1987-04-01

    Pulmonary functions, morphology, and morphometry were examined in rats at 3, 7, and 10 weeks after a single intratracheal administration of 6.5 units of porcine pancreatic elastase in order to obtain a model of pulmonary emphysema which would be suitable for studying the responses of emphysematous lungs to atmospheric pollutants. Functional residual capacity and residual volume of the elastase-treated rats increased at all the times studied, but their total lung capacity increased only at 7 and 10 weeks compared with those of the saline-treated control rats. The increase in static lung compliance and the decrease in peak flow and maximum flow at 50% of total lung capacity during forced expiration were also observed in all except the 3-week elastase animals. The elastase-treated lungs showed morphological changes characteristic of emphysematous lesions. The increase in mean linear intercept length and the decrease in total alveolar surface area were demonstrated by these elastase-treated lungs. Based on these results, they conclude that an adequate and suitable model of pulmonary emphysemia could be obtained in rats 7-10 weeks after treatment with the present dose of elastase.

  9. Local insulin therapy affects fracture healing in a rat model.

    PubMed

    Park, Andrew G; Paglia, David N; Al-Zube, Loay; Hreha, Jeremy; Vaidya, Swaroopa; Breitbart, Eric; Benevenia, Joseph; O'Connor, J Patrick; Lin, Sheldon S

    2013-05-01

    A significant number of lower extremity fractures result in mal-union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin-dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non-diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high-dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low-dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment.

  10. Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages.

    PubMed

    Jiang, Xingwei; Yu, Jiahui; Shi, Qingzhu; Xiao, Yan; Wang, Wei; Chen, Guojiang; Zhao, Zhi; Wang, Renxi; Xiao, He; Hou, Chunmei; Feng, Jiannan; Ma, Yuanfang; Shen, Beifen; Wang, Lili; Li, Yan; Han, Gencheng

    2015-10-01

    Tim-3 is involved in the physiopathology of inflammatory bowel disease (IBD), but the underlying mechanism is unknown. Here, we demonstrated that, in mouse with DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1 macrophages, while Tim-3 downregulation or blockade resulted in an increased M1 response. Adoptive transfer of Tim-3-silenced macrophages worsened DSS colitis and enhanced inflammation, while Tim-3 overexpression attenuated DSS colitis by decreasing the M1 macrophage response. Co-culture of Tim-3-overexpressing macrophages with intestinal lymphocytes decreased the pro-inflammatory response. Tim-3 shaped intestinal macrophage polarization may be TLR-4 dependent since Tim-3 blockade failed to exacerbate colitis or increase M1 macrophage response in the TLR-4 KO model. Finally, Tim-3 signaling inhibited phosphorylation of IRF3, a TLR-4 downstream transcriptional factor regulating macrophage polarization. A better understanding of this pathway may shed new light on colitis pathogenesis and result in a new therapeutic strategy.

  11. Myristica fragrans seed extract protects against dextran sulfate sodium-induced colitis in mice.

    PubMed

    Kim, Hyojung; Bu, Youngmin; Lee, Beom-Joon; Bae, Jinhyun; Park, Sujin; Kim, Jinsung; Lee, Kyungjin; Cha, Jae-Myung; Ryu, Bongha; Ko, Seok-Jae; Han, Gajin; Min, Byungil; Park, Jae-Woo

    2013-10-01

    Nutmeg (seed of Myristica fragrans [MF]) is one of the most commonly used spices in the world and also a well-known herb for the treatment of various intestinal diseases, including colitis in traditional Korean medicine. The purpose of the current study was to investigate whether water extract of MF (MFE) can protect against dextran sulfate sodium (DSS) induced colitis in a mouse model. Colitis was induced by 5% DSS in balb/c mice. MFE (100, 300 or 1000 mg/kg) was orally administered to the mice twice a day for 7 days. Body weight, colon length, clinical score, and histological score were assessed to determine the effects on colitis. Proinflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) were measured to investigate the mechanisms of action. MFE dose dependently inhibited the colon shortening and histological damage to the colon. However, it did not prevent weight loss. MFE also inhibited proinflammatory cytokines. The current results suggest that MFE ameliorates DSS-induced colitis in mice by inhibiting inflammatory cytokines. Further investigation, including the exact mechanisms is needed.

  12. ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis.

    PubMed

    Cabrera, Sandra; Fernández, Alvaro F; Mariño, Guillermo; Aguirre, Alina; Suárez, María F; Español, Yaiza; Vega, José A; Laurà, Rosaria; Fueyo, Antonio; Fernández-García, M Soledad; Freije, José M P; Kroemer, Guido; López-Otín, Carlos

    2013-08-01

    The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b (-/-) mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b (-/-) mice. Taken together, these results provided additional evidence for the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency.

  13. Complement component 6 deficiency increases susceptibility to dextran sulfate sodium-induced murine colitis.

    PubMed

    Ding, Peipei; Li, Ling; Huang, Tianbao; Yang, Chaoqun; Xu, Enjie; Wang, Na; Zhang, Long; Gu, Hongyu; Yao, Xudong; Zhou, Xuhui; Hu, Weiguo

    2016-11-01

    As a potent effector of innate immunity, the complement system has been shown to be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the role of the membrane attack complex (MAC) in the development of IBD is still largely unknown. Here, we used C6-deficient mice in which MAC formation was blocked due to the absence of C6 to develop an acute colitis model by the administration of dextran sulfate sodium (DSS). The results showed that DSS-induced colitis was aggravated in C6-deficient mice compared with wild-type (WT) mice, as represented by the markedly greater weight loss, higher disease activity index (DAI), shortened colon length, more severe histological injury with increased epithelial ulcerations, and massively increased infiltration of leukocytes accompanied by much higher myeloperoxidase (MPO) levels in local inflammatory colonic sites. In addition, the DSS-induced colitis in C6-deficient mice could be significantly ameliorated by the exogenous C6 from WT sera. Furthermore, the significantly enhanced production of pro-inflammatory mediators, including IL-1β, IL-6, CXCL-1, CCL-3, TGF-β1 and IL-17F, was also observed in C6-deficient mice. Unexpectedly, the aggravated colitis in C6-deficient mice may be not due to the increase of lipopolysaccharide (LPS) levels in serum. Overall, we demonstrated that MAC exerts a protective role in acute colitis, strongly highlighting the host defense function of the complement system. PMID:27316715

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

    PubMed Central

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

    2016-01-01

    This study investigates the in vivo functions of ginseng berry extract (GB) as a therapy for dextran sodium sulfate (DSS)-induced colitis. C57BL/6 mice were given drinking water containing DSS (3%) for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg) once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103−CD11c+ dendritic cells (cDCs), and macrophages. In addition, GB treatment promoted the migration of CD103+CD11c+ cDCs and expansion of Foxp3+ regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis. PMID:27058552

  15. ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis

    PubMed Central

    Cabrera, Sandra; Fernández, Álvaro F.; Mariño, Guillermo; Aguirre, Alina; Suárez, María F.; Español, Yaiza; Vega, José A.; Laurà, Rosaria; Fueyo, Antonio; Fernández-García, M. Soledad; Freije, José M.P.; Kroemer, Guido; López-Otín, Carlos

    2013-01-01

    The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b−/− mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b−/− mice. Taken together, these results provided additional evidence for the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency. PMID:23782979

  16. The matricellular protein CCN1 promotes mucosal healing in murine colitis through IL-6.

    PubMed

    Choi, J S; Kim, K-H; Lau, L F

    2015-11-01

    The matricellular protein CCN1 (CYR61) is known to function in wound healing and is upregulated in colons of patients with Crohn's disease and ulcerative colitis, yet its specific role in colitis is unknown. Here we have used Ccn1(dm/dm) knockin mice expressing a CCN1 mutant unable to bind integrins α6β1 and αMβ2 as a model to probe CCN1 function in dextran sodium sulfate (DSS)-induced colitis. Ccn1(dm/dm) mice exhibited high mortality, impaired mucosal healing, and diminished interleukin-6 (IL-6) expression during the repair phase of DSS-induced colitis compared with wild-type mice, despite having comparable severity of initial inflammation and tissue injury. CCN1-induced IL-6 expression in macrophages through integrin αMβ2 and in fibroblasts through α6β1, and IL-6 promoted intestinal epithelial cell (IEC) proliferation. Administration of purified CCN1 protein fully rescued Ccn1(dm/dm) mice from DSS-induced mortality, restored IEC proliferation and enhanced mucosal healing, whereas delivery of IL-6 partially rectified these defects. CCN1 therapy accelerated mucosal healing and recovery from DSS-induced colitis even in wild-type mice. These findings reveal a critical role for CCN1 in restoring mucosal homeostasis after intestinal injury in part through integrin-mediated induction of IL-6 expression, and suggest a therapeutic potential for activating the CCN1/IL-6 axis for treating inflammatory bowel disease.

  17. Myristica fragrans seed extract protects against dextran sulfate sodium-induced colitis in mice.

    PubMed

    Kim, Hyojung; Bu, Youngmin; Lee, Beom-Joon; Bae, Jinhyun; Park, Sujin; Kim, Jinsung; Lee, Kyungjin; Cha, Jae-Myung; Ryu, Bongha; Ko, Seok-Jae; Han, Gajin; Min, Byungil; Park, Jae-Woo

    2013-10-01

    Nutmeg (seed of Myristica fragrans [MF]) is one of the most commonly used spices in the world and also a well-known herb for the treatment of various intestinal diseases, including colitis in traditional Korean medicine. The purpose of the current study was to investigate whether water extract of MF (MFE) can protect against dextran sulfate sodium (DSS) induced colitis in a mouse model. Colitis was induced by 5% DSS in balb/c mice. MFE (100, 300 or 1000 mg/kg) was orally administered to the mice twice a day for 7 days. Body weight, colon length, clinical score, and histological score were assessed to determine the effects on colitis. Proinflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) were measured to investigate the mechanisms of action. MFE dose dependently inhibited the colon shortening and histological damage to the colon. However, it did not prevent weight loss. MFE also inhibited proinflammatory cytokines. The current results suggest that MFE ameliorates DSS-induced colitis in mice by inhibiting inflammatory cytokines. Further investigation, including the exact mechanisms is needed. PMID:24063406

  18. Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy

    EPA Science Inventory

    Ambient particulate matter (PM) exposure is linked to cardiovascular events and death, especially among individuals with heart disease. A model of toxic cardiomyopathy was developed in Spontaneously Hypertensive Heart Failure (SHHF) rats to explore potential mechanisms. Rats were...

  19. Intravenous Immunoglobulin in the Treatment of Severe Clostridium Difficile Colitis

    PubMed Central

    Shah, Nihar; Shaaban, Hamid; Spira, Robert; Slim, Jihad; Boghossian, Jack

    2014-01-01

    Intravenous immunoglobulin (IVIG) has been utilized in patients with recurrent and refractory Clostridium difficile colitis. It is increasingly being used in patients with initial clinical presentation of severe colitis. Herein, we report a case of severe C. Difficile colitis successfully treated with IVIG with a review of the medical literature to identify the optimal timing and clinical characteristics for this treatment strategy. PMID:24926170

  20. Segmental colitis associated diverticulosis syndrome

    PubMed Central

    Freeman, Hugh J

    2016-01-01

    Segmental colitis associated diverticulosis (SCAD) has become increasingly appreciated as a form of inflammatory disease of the colon. Several features suggest that SCAD is a distinct disorder. SCAD tends to develop almost exclusively in older adults, predominately, but not exclusively, males. The inflammatory process occurs mainly in the sigmoid colon, and usually remains localized to this region of the colon alone. SCAD most often presents with rectal bleeding and subsequent endoscopic visualization reveals a well localized process with non-specific histopathologic inflammatory changes. Granulomas are not seen, and if present, may be helpful in definition of other disorders such as Crohn’s disease of the colon, an entity often confused with SCAD. Bacteriologic and parasitic studies for an infectious agent are negative. Normal rectal mucosa (i.e., “rectal sparing”) is present and can be confirmed with normal rectal biopsies. SCAD often resolves spontaneously without treatment, or completely after a limited course of therapy with only a 5-aminosalicylate. Recurrent episodes may occur, but most often, patients with this disorder have an entirely self-limited clinical course. Occasionally, treatment with other agents, including corticosteroids, or surgical resection has been required.

  1. Segmental colitis associated diverticulosis syndrome.

    PubMed

    Freeman, Hugh J

    2016-09-28

    Segmental colitis associated diverticulosis (SCAD) has become increasingly appreciated as a form of inflammatory disease of the colon. Several features suggest that SCAD is a distinct disorder. SCAD tends to develop almost exclusively in older adults, predominately, but not exclusively, males. The inflammatory process occurs mainly in the sigmoid colon, and usually remains localized to this region of the colon alone. SCAD most often presents with rectal bleeding and subsequent endoscopic visualization reveals a well localized process with non-specific histopathologic inflammatory changes. Granulomas are not seen, and if present, may be helpful in definition of other disorders such as Crohn's disease of the colon, an entity often confused with SCAD. Bacteriologic and parasitic studies for an infectious agent are negative. Normal rectal mucosa (i.e., "rectal sparing") is present and can be confirmed with normal rectal biopsies. SCAD often resolves spontaneously without treatment, or completely after a limited course of therapy with only a 5-aminosalicylate. Recurrent episodes may occur, but most often, patients with this disorder have an entirely self-limited clinical course. Occasionally, treatment with other agents, including corticosteroids, or surgical resection has been required. PMID:27688648

  2. [Antibiotic treatment of clostridial colitis].

    PubMed

    Beneš, J; Polívková, S

    2016-01-01

    The advantages and disadvantages of various antibiotics used in the treatment of Clostridium difficile infection (CDI) are compared with respect to their pharmacokinetic and pharmacodynamic properties. Recommendations are made for their optimal use in clinical practice. Metronidazole is suitable for the treatment of mild forms of CDI which are essentially self-limiting. Vancomycin kills clostridia reliably but the treatment is encumbered with considerable risk of recurrence. This can be decreased by shortening the treatment to seven days and then switching to a (pulse, taper, chaser) regimen to prevent recurrence or by active restoration of the intestinal ecosystem (fecal transplant). Fidaxomicin works faster than vancomycin and is associated with a lower risk of recurrence. Thus, it can be profitably used in patients with impending ileus and also in those whose medical condition does not allow prolonged treatment. The duration of fidaxomicin treatment could be reduced to as few as five days. Rifaximin does not have a clear place in the treatment of CDI because no compelling data are available on its efficacy in this disease. The risk of resistance is also important. Tigecycline is a promising antibiotic for parenteral use. According to the available data, it should be more effective than intravenous metronidazole which has been considered the drug of choice.Clostridial colitis is associated with intestinal dysmicrobia which is the major cause of recurrence. Severe dysmicrobia cannot be treated by antibiotics but only by gut flora restoration; stool transplant from a healthy donor is the only proven therapy for this condition. PMID:27246640

  3. Segmental colitis associated diverticulosis syndrome

    PubMed Central

    Freeman, Hugh J

    2016-01-01

    Segmental colitis associated diverticulosis (SCAD) has become increasingly appreciated as a form of inflammatory disease of the colon. Several features suggest that SCAD is a distinct disorder. SCAD tends to develop almost exclusively in older adults, predominately, but not exclusively, males. The inflammatory process occurs mainly in the sigmoid colon, and usually remains localized to this region of the colon alone. SCAD most often presents with rectal bleeding and subsequent endoscopic visualization reveals a well localized process with non-specific histopathologic inflammatory changes. Granulomas are not seen, and if present, may be helpful in definition of other disorders such as Crohn’s disease of the colon, an entity often confused with SCAD. Bacteriologic and parasitic studies for an infectious agent are negative. Normal rectal mucosa (i.e., “rectal sparing”) is present and can be confirmed with normal rectal biopsies. SCAD often resolves spontaneously without treatment, or completely after a limited course of therapy with only a 5-aminosalicylate. Recurrent episodes may occur, but most often, patients with this disorder have an entirely self-limited clinical course. Occasionally, treatment with other agents, including corticosteroids, or surgical resection has been required. PMID:27688648

  4. A New Rat Model for Orthotopic Abdominal Wall Allotransplantation

    PubMed Central

    Lao, William W.; Wang, Yen-Ling; Ramirez, Alejandro E.; Cheng, Hui-Yun

    2014-01-01

    Background: Abdominal wall, one of the most commonly transplanted composite tissues, is less researched and lacking animal models. Its clinical necessities were emphasized in multiple case series to reconstruct large abdominal defects. Previous animal models have only studied components of the abdominal wall transplant. We describe findings from a new model that more likely reflect clinical transplantation. Methods: Full-thickness hemiabdominal wall flap was procured from Brown Norway (BN) rats and transplanted to an orthotopic defect on Lewis rats. Three groups were studied: group 1: Lewis to Lewis syngeneic; group 2: BN to Lewis control; and group 3: BN to Lewis with postoperative cyclosporine. Vascular imaging and cross vessel section were performed along with full-thickness abdominal wall. Immune cell profiling with flow cytometry at different time points was studied in all groups. Results: Syngeneic group had no rejection. Control group consistently showed rejection around postoperative day 6. With cyclosporine treatment, however, transplant and recipient tissue integration was observed. Flow cytometry revealed that innate immunity is responsible for the initial inflammatory events following abdominal wall engraftment. Adaptive immunity cells, specifically interferon-γ-producing T helper (Th) 1 and interleukin-17-producing Th17 cells, dramatically and positively correlate with rejection progression of abdominal wall transplants. Conclusions: Technical, histological, and immunological aspects of a new rat model are described. These results give clues to what occurs in human abdominal wall transplantation. In addition, Th1, a proinflammatory cell, was found to be a potential biomarker for allograft rejection. PMID:25289329

  5. Creation of Consistent Burn Wounds: A Rat Model

    PubMed Central

    Cai, Elijah Zhengyang; Ang, Chuan Han; Raju, Ashvin; Tan, Kong Bing; Hing, Eileen Chor Hoong; Loo, Yihua; Wong, Yong Chiat; Lee, Hanjing; Lim, Jane; Moochhala, Shabbir M; Hauser, Charlotte AE

    2014-01-01

    Background Burn infliction techniques are poorly described in rat models. An accurate study can only be achieved with wounds that are uniform in size and depth. We describe a simple reproducible method for creating consistent burn wounds in rats. Methods Ten male Sprague-Dawley rats were anesthetized and dorsum shaved. A 100 g cylindrical stainless-steel rod (1 cm diameter) was heated to 100℃ in boiling water. Temperature was monitored using a thermocouple. We performed two consecutive toe-pinch tests on different limbs to assess the depth of sedation. Burn infliction was limited to the loin. The skin was pulled upwards, away from the underlying viscera, creating a flat surface. The rod rested on its own weight for 5, 10, and 20 seconds at three different sites on each rat. Wounds were evaluated for size, morphology and depth. Results Average wound size was 0.9957 cm2 (standard deviation [SD] 0.1845) (n=30). Wounds created with duration of 5 seconds were pale, with an indistinct margin of erythema. Wounds of 10 and 20 seconds were well-defined, uniformly brown with a rim of erythema. Average depths of tissue damage were 1.30 mm (SD 0.424), 2.35 mm (SD 0.071), and 2.60 mm (SD 0.283) for duration of 5, 10, 20 seconds respectively. Burn duration of 5 seconds resulted in full-thickness damage. Burn duration of 10 seconds and 20 seconds resulted in full-thickness damage, involving subjacent skeletal muscle. Conclusions This is a simple reproducible method for creating burn wounds consistent in size and depth in a rat burn model. PMID:25075351

  6. Nitric oxide increases Wnt-induced secreted protein-1 (WISP-1/CCN4) expression and function in colitis.

    PubMed

    Wang, Hongying; Zhang, Rui; Wen, Shoubin; McCafferty, Donna-Marie; Beck, Paul L; MacNaughton, Wallace K

    2009-04-01

    Nitric oxide (NO) derived from the inducible NO synthase (iNOS) is an important and complex mediator of inflammation in the intestine. Wnt-inducible secreted protein (WISP)-1 (CCN4), a member of the connective tissue growth factor family, is involved in tissue repair. We sought to determine the relationship between iNOS and WISP-1 in colitis. By analyzing human colonic biopsy samples, we showed that the expression of mRNA for both iNOS and WISP-1 was significantly higher in ulcerative colitis samples compared with control tissue. The upregulation of WISP-1 was positively correlated with iNOS expression in two models of colitis, induced by intrarectal trinitrobenzenesulfonic acid (TNBS) or occurring spontaneously in IL-10 deficient mice. Loss of iNOS, studied using iNOS(-/-) mice in both TNBS-induced and IL-10(-/-) colitis models, significantly attenuated the colitis-related WISP-1 increase. In human colonic epithelial cell lines, the NO donor, DETA-NONOate, elevated WISP-1 mRNA and protein expression through a beta-catenin and CREB-dependent, but Wnt-1-independent, pathway. In addition, NO-induced WISP-1 directly induced secretion of soluble collagen in colonic fibroblast cells. NO increases WISP-1 expression both in vitro and in vivo, suggesting a new role for iNOS and NO in colitis.

  7. Boehmeria nivea Attenuates the Development of Dextran Sulfate Sodium-Induced Experimental Colitis

    PubMed Central

    Shin, Eun Ju; Sung, Mi Jeong; Yang, Hye Jeong; Kim, Myung Sunny; Hwang, Jin-Taek

    2014-01-01

    We examined the therapeutic effect of an ethanol extract derived from Boehmeria nivea (Linn.) Gaudich in a mouse model of experimental colitis. Treatment with 70% ethanol extract derived from B. nivea (EBN) at a dose of 100, 200, or 500 mg/(kg·d) improved colon shortening, body weight, the disease activity index (DAI), and histopathological score of DSS-induced colitis mice. DSS significantly increased the levels of cyclooxygenase-(COX-) 2 in colon tissue relative to that of the untreated control group. EBN administered at 100, 200, or 500 mg/(kg·d) reduced COX-2 levels in the DSS-treated mice. In addition, EBN decreased the DSS-induced secretion of the inflammatory cytokine interleukin-6 (IL-6) and chemokine monocyte chemotactic protein-1 (MCP-1). Taken together, these data suggest that B. nivea extract is effective in preventing colitis. PMID:25045208

  8. Role and species–specific expression of colon T cell homing receptor GPR15 in colitis

    PubMed Central

    Nguyen, Linh P.; Pan, Junliang; Dinh, Theresa Thanh; Hadeiba, Husein; O’Hara, Edward; Ebtikar, Ahmad; Hertweck, Arnulf; Gökmen, M. Refik; Lord, Graham M.; Jenner, Richard G.

    2014-01-01

    Lymphocyte recruitment maintains intestinal immune homeostasis but also contributes to inflammation. The orphan chemoattractant receptor GPR15 mediates regulatory T cell homing and immunosuppression in the mouse colon. We show that GPR15 is also expressed by mouse TH17 and TH1 effector cells, and is required for colitis in a model that depends on their trafficking to the colon. In humans GPR15 is expressed by effector cells including pathogenic TH2 cells in ulcerative colitis, but is not expressed by regulatory T (Treg) cells. The TH2 transcriptional activator GATA-3 and the Treg–associated transcriptional repressor FOXP3 robustly bind human, but not mouse, GPR15 enhancer sequences, correlating with expression. Our results highlight species differences in GPR15 regulation, and suggest it as a potential therapeutic target for colitis. PMID:25531831

  9. Neutrophils Are a Source of Gamma Interferon during Acute Salmonella enterica Serovar Typhimurium Colitis

    PubMed Central

    Spees, Alanna M.; Kingsbury, Dawn D.; Wangdi, Tamding; Xavier, Mariana N.; Tsolis, Renée M.

    2014-01-01

    Gamma interferon (IFN-γ) is an important driver of intestinal inflammation during colitis caused by Salmonella enterica serovar Typhimurium. Here we used the mouse colitis model to investigate the cellular sources of IFN-γ in the cecal mucosa during the acute phase of an S. Typhimurium infection. While IFN-γ staining was detected in T cells, NK cells, and inflammatory monocytes at 2 days after infection, the majority of IFN-γ-positive cells in the cecal mucosa were neutrophils. Furthermore, neutrophil depletion blunted mucosal Ifng expression and reduced the severity of intestinal lesions during S. Typhimurium infection. We conclude that neutrophils are a prominent cellular source of IFN-γ during the innate phase of S. Typhimurium-induced colitis. PMID:24421037

  10. Ventricular repolarization in a rat model of global heart failure.

    PubMed

    Krandycheva, Valeria; Kharin, Sergey; Strelkova, Marina; Shumikhin, Konstantin; Sobolev, Aleksey; Shmakov, Dmitry

    2013-07-01

    Isoproterenol in high doses induces infarction-like myocardial damage and structural and functional remodelling of the ventricular myocardium. The purpose of the present study was to investigate ventricular repolarization in a rat model of isoproterenol-induced heart failure. Isoproterenol was administered twice to female Wistar rats (170 mg/kg, s.c., 24 h apart). Four weeks after the injections, cardiac output was measured and unipolar epicardial ventricular electrograms were recorded in situ. Activation-recovery intervals were calculated to assess repolarization. Histological examination of the heart ventricles was also performed. Heart failure in rats treated with isoproterenol was indicated by myocardial histopathological damage and reduced cardiac output. In rats with heart failure, the regional differences in activation-recovery interval prolongation over the ventricular epicardium resulted in increasing heterogeneity in the activation-recovery interval distribution and increasing repolarization heterogeneity of the ventricular subepicardium. Myocardial damage and haemodynamic changes in heart failure induced by isoproterenol were accompanied by significant changes in ventricular repolarization, which were not associated with myocardial hypertrophy.

  11. A simple and stable galactosemic cataract model for rats

    PubMed Central

    Ji, Lixia; Li, Caina; Shen, Ning; Huan, Yi; Liu, Quan; Liu, Shuainan; Shen, Zhufang

    2015-01-01

    Rat galactosemic cataract is commonly used in the investigation of sugar cataract. In current study, 21-day sprague-dawley (SD) rats were randomly divided into two groups (n=42), which were fed by normal water and galactose solution (12.5%-10%) for 18 days respectively. Every 3 days, lens opacity was observed by a slit lamp, and 6 rats of each group were executed for the analysis of aldose reductase (AR) activity, galactitol level and AR mRNA expression. Morphological results showed that small vacuoles initially appeared in the equatorial area before the 6th day, then subsequently extended to the whole anterior capsule, and eventually developed to mature cataract on the 18th day. AR of galactosemic lenses was significantly activated in the first stage and then slowly dropped to the end accompanied by the related changes of galactitol. AR mRNA expression also was upregulated and reached the peak at the 6th day. This study appears to confirm that galactosemic cataract can be induced for 21-day SD rats by only drinking 12.5% to 10% galactose solution, and this model is simple, economical and stable as to meet the research needs. PMID:26550203

  12. A simple and stable galactosemic cataract model for rats.

    PubMed

    Ji, Lixia; Li, Caina; Shen, Ning; Huan, Yi; Liu, Quan; Liu, Shuainan; Shen, Zhufang

    2015-01-01

    Rat galactosemic cataract is commonly used in the investigation of sugar cataract. In current study, 21-day sprague-dawley (SD) rats were randomly divided into two groups (n=42), which were fed by normal water and galactose solution (12.5%-10%) for 18 days respectively. Every 3 days, lens opacity was observed by a slit lamp, and 6 rats of each group were executed for the analysis of aldose reductase (AR) activity, galactitol level and AR mRNA expression. Morphological results showed that small vacuoles initially appeared in the equatorial area before the 6th day, then subsequently extended to the whole anterior capsule, and eventually developed to mature cataract on the 18th day. AR of galactosemic lenses was significantly activated in the first stage and then slowly dropped to the end accompanied by the related changes of galactitol. AR mRNA expression also was upregulated and reached the peak at the 6th day. This study appears to confirm that galactosemic cataract can be induced for 21-day SD rats by only drinking 12.5% to 10% galactose solution, and this model is simple, economical and stable as to meet the research needs.

  13. Arsenic and chromium in drinking water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/β-catenin signaling pathway

    SciTech Connect

    Wang, Xin; Mandal, Ardhendu K.; Saito, Hiroshi; Pulliam, Joseph F.; Lee, Eun Y.; Ke, Zun-Ji; Lu, Jian; Ding, Songze; Li, Li; Shelton, Brent J.; Tucker, Thomas; Evers, B. Mark; Zhang, Zhuo; Shi, Xianglin

    2012-07-01

    Exposure to carcinogenic metals, such as trivalent arsenic [As(III)] and hexavalent chromium [Cr(VI)], through drinking water is a major global public health problem and is associated with various cancers. However, the mechanism of their carcinogenicity remains unclear. In this study, we used azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse colitis-associated colorectal cancer model to investigate their tumorigenesis. Our results demonstrate that exposure to As(III) or Cr(VI), alone or in combination, together with AOM/DSS pretreatment has a promotion effect, increasing the colorectal tumor incidence, multiplicity, size, and grade, as well as cell inflammatory response. Two-dimensional differential gel electrophoresis coupled with mass spectrometry revealed that As(III) or Cr(VI) treatment alone significantly changed the density of proteins. The expression of β-catenin and phospho-GSK was increased by treatment of carcinogenic metals alone. Concomitantly, the expression of NADPH oxidase1 (NOX1) and the level of 8-OHdG were also increased by treatment of carcinogenic metals alone. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, were decreased. Similarly, in an in vitro system, exposure of CRL-1807 to carcinogenic metals increased reactive oxygen species (ROS) generation, the expression of β-catenin, phospho-GSK, and NOX1. Inhibition of ROS generation by addition of SOD or catalase inhibited β-catenin expression and activity. Our study provides a new animal model to study the carcinogenicity of As(III) and Cr(VI) and suggests that As(III) and Cr(VI) promote colorectal cancer tumorigenesis, at least partly, through ROS-mediated Wnt/β-catenin signaling pathway. -- Highlights: ► Carcinogenic metals in drinking water promote colorectal tumor formation in vivo. ► Carcinogenic metals induce β-catenin activation in vivo and in vitro. ► ROS generation induced by carcinogenic metals mediated β-catenin activation.

  14. Arsenic and chromium in drinking water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/β-catenin signaling pathway

    PubMed Central

    Wang, Xin; Mandal, Ardhendu K.; Saito, Hiroshi; Pulliam, Joseph F.; Lee, Eun Y.; Ke, Zun-Ji; Lu, Jian; Ding, Songze; Li, Li; Shelton, Brent J; Tucker, Thomas; Evers, B. Mark; Zhang, Zhuo; Shi, Xianglin

    2015-01-01

    Exposure to carcinogenic metals, such as trivalent arsenic [As(III)] and hexavalent chromium [Cr(VI)], through drinking water is a major global public health problem and is associated with various cancers. However, the mechanism of their carcinogenicity remains unclear. In this study, we used azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse colitis-associated colorectal cancer model to investigate their tumorigenesis. Our results demonstrate that exposure to As(III) or Cr(VI), alone or in combination, together with AOM/DSS pretreatment has a promotion effect, increasing the colorectal tumor incidence, multiplicity, size, and grade, as well as cell inflammatory response. Two-dimensional differential gel electrophoresis coupled with mass spectrometry revealed that As(III) or Cr(VI) treatment alone significantly changed the density of proteins. The expression of β-catenin and phospho-GSK was increased by treatment of carcinogenic metals alone. Concomitantly, the expression of NADPH oxidase1 (NOX1) and the level of 8-OHdG were also increased by treatment of carcinogenic metals alone. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, were decreased. Similarly, in an in vitro system, exposure of CRL-1807 to carcinogenic metals increased reactive oxygen species (ROS) generation, the expression of β-catenin, phospho-GSK, and NOX1. Inhibition of ROS generation by addition of SOD or catalase inhibited β-catenin expression and activity. Our study provides a new animal model to study the carcinogenicity of As(III) and Cr(VI) and suggest that As(III) and Cr(VI) promote colorectal cancer tumorigenesis, at least partly, through ROS-mediated Wnt/β-catenin signaling pathway. PMID:22552367

  15. Arsenic and chromium in drinking water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/β-catenin signaling pathway.

    PubMed

    Wang, Xin; Mandal, Ardhendu K; Saito, Hiroshi; Pulliam, Joseph F; Lee, Eun Y; Ke, Zun-Ji; Lu, Jian; Ding, Songze; Li, Li; Shelton, Brent J; Tucker, Thomas; Evers, B Mark; Zhang, Zhuo; Shi, Xianglin

    2012-07-01

    Exposure to carcinogenic metals, such as trivalent arsenic [As(III)] and hexavalent chromium [Cr(VI)], through drinking water is a major global public health problem and is associated with various cancers. However, the mechanism of their carcinogenicity remains unclear. In this study, we used azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse colitis-associated colorectal cancer model to investigate their tumorigenesis. Our results demonstrate that exposure to As(III) or Cr(VI), alone or in combination, together with AOM/DSS pretreatment has a promotion effect, increasing the colorectal tumor incidence, multiplicity, size, and grade, as well as cell inflammatory response. Two-dimensional differential gel electrophoresis coupled with mass spectrometry revealed that As(III) or Cr(VI) treatment alone significantly changed the density of proteins. The expression of β-catenin and phospho-GSK was increased by treatment of carcinogenic metals alone. Concomitantly, the expression of NADPH oxidase1 (NOX1) and the level of 8-OHdG were also increased by treatment of carcinogenic metals alone. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, were decreased. Similarly, in an in vitro system, exposure of CRL-1807 to carcinogenic metals increased reactive oxygen species (ROS) generation, the expression of β-catenin, phospho-GSK, and NOX1. Inhibition of ROS generation by addition of SOD or catalase inhibited β-catenin expression and activity. Our study provides a new animal model to study the carcinogenicity of As(III) and Cr(VI) and suggests that As(III) and Cr(VI) promote colorectal cancer tumorigenesis, at least partly, through ROS-mediated Wnt/β-catenin signaling pathway.

  16. Healing effects of Aegle marmelos (L.) Correa fruit extract on experimental colitis.

    PubMed

    Gautam, M K; Ghatule, R R; Singh, A; Purohit, V; Gangwar, M; Kumar, Mohan; Goel, R K

    2013-02-01

    Graded doses of 50% ethanolic extract of dried fruit pulp of Aegle marmelos (AME) (100, 200 and 400 mg/kg) daily for 14 days in acetic acid (AA)-induced colitis in rats showed 200 mg/kg of AME as an optimal effective dose against AA-induced colonic damage score and weight. This dose (200 mg/kg; po) was further studied in AA-induced colitis for its effects on various physical (mucous/blood in stool, food and water intake and body weight changes), histology, antibacterial activity and biochemical parameters like free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and myeloperoxidase (acute-inflammatory marker) activities in rat colonic tissue. AME decreased colonic mucosal damage and inflammation (macroscopic and microscopic), mucous/bloody diarrhea, fecal frequency and increased body weight affected in AA-induced colitis. AME showed significant antibacterial activity and enhanced the antioxidants but decreased free radicals and myeloperoxidase activities thereby decreasing tissue damage and inflammation and thus, affording ulcer healing. The above effects of A. marmelos authenticated its use in indigenous system of Medicine. PMID:23923609

  17. Capsular Contracture In Silicone Breast Implants: Insights From Rat Models.

    PubMed

    Vieira, Vilberto J; D'Acampora, Armando; Neves, Fernanda S; Mendes, Paulo R; Vasconcellos, Zulmar A DE; Neves, Rodrigo D'Eça; Figueiredo, Claudia P

    2016-09-01

    Breast augmentation with silicone implants is one of the most common procedures performed by plastic surgeons around the world. Capsular contracture is a frequent complication in breast augmentation and reconstructive surgery, that requires invasive intervention. The inflammatory response to implanted mammary prostheses appears to be directly associated to capsular contracture. This review discusses the evidences from rat models studies, on the role of inflammation and fibrosis in capsular contraction and its relation to silicone breast implants surface. PMID:27627068

  18. [Establishment of a rat chronic asthma model and its evaluation].

    PubMed

    Liu, Zhong-Cheng; Zhang, Yan-Fen

    2010-06-01

    This study is to establish a rat chronic asthma model. Sensitive SD rats were selected through histamine challenge. The asthmatic groups were sensitized by ih and ip with OVA, aluminium hydroxide gel and inactivated bacillus pertussis on day 1 and 14. From day 21, acute asthmatic group was aerosolized 1% OVA for 1 week, chronic asthmatic group was aerosolized 0.1% OVA for 12 weeks. The control groups received saline as the substitution of OVA. Twenty four hours after the last provocation, physiological monitoring equipment was used to detect the pulmonary function, then the rats were sacrificed. Bronchoalveolar lavage fluid (BALF) was collected to calculate the ratio of different inflammatory cells. ELISA was used to detect total IgE and OVA-specific IgE in serum. Microscopy was conducted to observe the histopathology of lung stained with haematoxylin and eosin staining. Collagen fibers were detected using Picric acid-Sirius red staining technique. The optical density at 610 nm of extractive from locus caeruleus was detected by passive cutaneous anaphylaxis (PCA). The results showed that the asthmatic characteristics were significantly developed in model groups, but not in control groups. Chronic asthmatic group had significantly higher indexes than acute asthmatic group, including the thickness of airway smooth muscle and bronchial basement membrane, and goblet cell hyperplasia, the area of collagen in airways, A610 of extractive from locus caeruleus, the concentration of total IgE and OVA-specific IgE in serum. However, inflammatory cell infiltrate in lungs and the percentage of eosinophils of white blood cells in BALF were lower in chronic asthmatic group than those in acute asthmatic group. Respiratory rate and respiratory flow showed no significant difference in both model groups. In conclusion, the rat chronic asthma model is established by the way in this study, which is comparable to the physiopathologic characteristics of human asthma.

  19. Advances in endoscopic imaging in ulcerative colitis.

    PubMed

    Tontini, Gian Eugenio; Pastorelli, Luca; Ishaq, Sauid; Neumann, Helmut

    2015-01-01

    Modern strategies for the treatment of ulcerative colitis require more accurate tools for gastrointestinal imaging to better assess mucosal disease activity and long-term prognostic clinical outcomes. Recent advances in gastrointestinal luminal endoscopy are radically changing the role of endoscopy in every-day clinical practice and research trials. Advanced endoscopic imaging techniques including high-definition endoscopes, optical magnification endoscopy, and various chromoendoscopy techniques have remarkably improved endoscopic assessment of ulcerative colitis. More recently, optical biopsy techniques with either endocytoscopy or confocal laser endomicroscopy have shown great potential in predicting several histological changes in real time during ongoing endoscopy. Here, we review current applications of advanced endoscopic imaging techniques in ulcerative colitis and present the most promising upcoming headways in this field. PMID:26365308

  20. Amyloid Goiter Secondary to Ulcerative Colitis.

    PubMed

    Aydin, Bunyamin; Koca, Yavuz Savas; Koca, Tugba; Yildiz, Ihsan; Gerek Celikden, Sevda; Ciris, Metin

    2016-01-01

    Diffuse amyloid goiter (AG) is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn's disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis. PMID:27051538

  1. Biomarkers for colitis-associated colorectal cancer.

    PubMed

    Chen, Ru; Lai, Lisa A; Brentnall, Teresa A; Pan, Sheng

    2016-09-21

    Patients with extensive ulcerative colitis (UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques - including cutting-edge OMICS technologies - recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer. PMID:27672285

  2. Biomarkers for colitis-associated colorectal cancer

    PubMed Central

    Chen, Ru; Lai, Lisa A; Brentnall, Teresa A; Pan, Sheng

    2016-01-01

    Patients with extensive ulcerative colitis (UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques - including cutting-edge OMICS technologies - recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer. PMID:27672285

  3. Biomarkers for colitis-associated colorectal cancer

    PubMed Central

    Chen, Ru; Lai, Lisa A; Brentnall, Teresa A; Pan, Sheng

    2016-01-01

    Patients with extensive ulcerative colitis (UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques - including cutting-edge OMICS technologies - recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer.

  4. Collagenous gastritis associated with lymphocytic colitis.

    PubMed

    Groisman, G M; Meyers, S; Harpaz, N

    1996-03-01

    Collagenous sprue and collagenous colitis are two well-recognized idiopathic enteritides whose defining histologic attribute is fibrous thickening of the subepithelial basement membrane. Analogous changes in gastric mucosa seem to be quite rare. The term "collagenous gastritis" was recently applied for the first time to an isolated case of refractory gastritis in which distinctive subepithelial gastric fibrosis was noted. We report an additional case of this entity in a 35-year-old woman with refractory dyspepsia. In contrast to the earlier case of collagenous gastritis, our patient also had lymphocytic colitis, a type of colitis associated with watery diarrhea. Collagenous gastritis appears to be a distinct clinicopathologic entity, the histologic changes of which should be sought in patients with unexplained dyspepsia. Increased awareness of this condition and its possible clinical correlates may provide clues to its etiology and pathogenesis. PMID:8742654

  5. Culture Model of Rat Portal Myofibroblasts

    PubMed Central

    El Mourabit, Haquima; Loeuillard, Emilien; Lemoinne, Sara; Cadoret, Axelle; Housset, Chantal

    2016-01-01

    Myofibroblasts are matrix-producing cells with contractile properties, usually characterized by de novo expression of alpha-smooth muscle actin, that arise in fibrotic diseases. Hepatic stellate cells (HSCs), known as perisinusoidal cells containing auto-fluorescent vitamin A, are the major although not exclusive source of myofibroblasts in the injured liver. Portal myofibroblasts (PMFs) have been defined as liver myofibroblasts derived from cells that are distinct from HSCs and located in the portal tract. Here, we describe the protocol we have established to obtain rat PMFs in culture. In this method, the biliary tree is (i) separated from the liver parenchyma by in situ enzymatic perfusion of the liver, (ii) minced and further digested in vitro, until bile duct segments are isolated by sequential filtration. Bile duct isolates free of HSC contaminants, form small cell clusters, which initially comprise a large majority of epithelial cells. In culture conditions (fetal bovine serum) that provide a growth advantage to mesenchymal cells over epithelial cells, the epithelial cells die and detach from the substrate, while spindle-shaped cells outgrow from the periphery of the cell clusters, as shown by video-microscopy. These cells are highly proliferative and after 4–5 days, the culture is composed exclusively of fully differentiated myofibroblasts, which express alpha-smooth muscle actin and collagen 1, and secrete abundant collagen. We found no evidence for epithelial-mesenchymal transition, i.e., no co-expression of alpha-smooth muscle actin and cytokeratin at any stage, while cytokeratin becomes undetectable in the confluent cells. PMFs obtained by this method express the genes that were previously reported to be overexpressed in non-HSC or portal fibroblast-derived liver myofibroblasts as compared to HSC-derived myofibroblasts, including the most discriminant, collagen 15, fibulin 2, and Thy-1. After one passage, PMFs retain the same phenotypic features as in

  6. Effects of obesity on severity of colitis and cytokine expression in mouse mesenteric fat. Potential role of adiponectin receptor 1.

    PubMed

    Sideri, Aristea; Stavrakis, Dimitris; Bowe, Collin; Shih, David Q; Fleshner, Phillip; Arsenescu, Violeta; Arsenescu, Razvan; Turner, Jerrold R; Pothoulakis, Charalabos; Karagiannides, Iordanes

    2015-04-01

    In inflammatory bowel disease (IBD), obesity is associated with worsening of the course of disease. Here, we examined the role of obesity in the development of colitis and studied mesenteric fat-epithelial cell interactions in patients with IBD. We combined the diet-induce obesity with the trinitrobenzene sulfonic acid (TNBS) colitis mouse model to create groups with obesity, colitis, and their combination. Changes in the mesenteric fat and intestine were assessed by histology, myeloperoxidase assay, and cytokine mRNA expression by real-time PCR. Medium from human mesenteric fat and cultured preadipocytes was obtained from obese patients and those with IBD. Histological analysis showed inflammatory cell infiltrate and increased histological damage in the intestine and mesenteric fat of obese mice with colitis compared with all other groups. Obesity also increased the expression of proinflammatory cytokines including IL-1β, TNF-α, monocyte chemoattractant protein 1, and keratinocyte-derived chemokine, while it decreased the TNBS-induced increases in IL-2 and IFN-γ in mesenteric adipose and intestinal tissues. Human mesenteric fat isolated from obese patients and those with and IBD demonstrated differential release of adipokines and growth factors compared with controls. Fat-conditioned media reduced adiponectin receptor 1 (AdipoR1) expression in human NCM460 colonic epithelial cells. AdipoR1 intracolonic silencing in mice exacerbated TNBS-induced colitis. In conclusion, obesity worsens the outcome of experimental colitis, and obesity- and IBD-associated changes in adipose tissue promote differential mediator release in mesenteric fat that modulates colonocyte responses and may affect the course of colitis. Our results also suggest an important role for AdipoR1 for the fat-intestinal axis in the regulation of inflammation during colitis.

  7. Exacerbation of oxazolone colitis by infection with the helminth Hymenolepis diminuta: involvement of IL-5 and eosinophils.

    PubMed

    Wang, Arthur; Fernando, Maria; Leung, Gabriella; Phan, Van; Smyth, David; McKay, Derek M

    2010-12-01

    Substantial data show that infection with helminth parasites ameliorates colitis; however, oxazolone-induced colitis is exaggerated in mice infected with the tapeworm, Hymenolepis diminuta. We tested the hypothesis that the IL-5 response to helminth infection enhances the severity of oxazolone-induced colitis. Mice were infected with H. diminuta and 8 days later were treated with oxazolone ± anti-IL-5 antibodies. Colitis was assessed 72 hours postoxazolone treatment by disease activity scores, myeloperoxidase activity, and histopathology. Other mice received injections of a replication-deficient adenovirus that carried the IL-5 (Ad.IL-5) gene or a control adenovirus (Ad.delete) ± oxazolone. The effect of H. diminuta+oxazolone in CCL11/CCL22 (eotaxin-1 and 2) knockout (KO) mice was determined. Helminth infection and Ad.IL-5 treatment increased IL-5 and eosinophil numbers. In vivo neutralization of IL-5 significantly reduced the severity of colitis in H. diminuta+oxazolone-treated mice, and H. diminuta did not exaggerate oxazolone-induced colitis in CCL11/CCL22 KO mice. Mice receiving Ad.IL-5 only had no colitis, while oxazolone-induced colitis was more severe in animals cotreated with Ad.IL-5 (Ad.delete + oxazolone was not significantly different from oxazolone only). Thus, while there is much to be gleaned about antiinflammatory mechanisms from rodent-helminth model systems, these data illustrate the caveat that infection with helminth parasites as a therapy could be contraindicated in patients with eosinophilia or elevated IL-5 unless coupled to appropriate measures to block IL-5 and/or eosinophil activity.

  8. Expression of the novel adipokine C1qTNF-related protein 4 (CTRP4) suppresses colitis and colitis-associated colorectal cancer in mice

    PubMed Central

    Luo, Yang; Wu, Xiaotong; Ma, Zhuang; Tan, Weifeng; Wang, Lanlan; Na, Daxiang; Zhang, Guoying; Yin, Ang; Huang, He; Xia, Dan; Zhang, Yingmei; Shi, Xueying; Wang, Lu

    2016-01-01

    Inflammatory bowel disease (IBD) is an important factor in the induction of colon cancer, but its mechanism is unclear. Colitis and colitis-associated colorectal cancer (CAC) models induced using both dextran sulfate sodium (DSS) and the azoxymethane/DSS protocol were established in wild-type (WT) and CTRP4 transgenic (CTRP4-tg) C57BL6/J mice. Body weight, stool consistency and the presence of blood in the stool were analyzed; tumor quantity, size and histological characteristics were analyzed during the development of CAC. The CTRP4-tg mice exhibited significantly reduced colitis and developed far fewer macroscopic tumors; these tumors were smaller in size, and a majority of the colon tumors in these mice were restricted to the superficial mucosa. Tumors of lower grades were observed in the CTRP4-tg mice. Interleukin-6 was markedly downregulated in the CTRP4-tg mice during CAC tumorigenesis. The phosphorylation of ERK, signal transducer and activator of transcription 3 and Akt in the colon and the proliferation of intestinal epithelial cells were decreased in the CTRP4-tg mice. The injection of recombinant CTRP4 protein significantly reduced the colitis symptoms of the WT mice. CTRP4 plays an important role in inflammation and inflammation-associated colon tumorigenesis, and our research may provide a novel method for the treatment of IBD and CAC. PMID:27086950

  9. Characterization of an animal model of postmenopausal hypertension in spontaneously hypertensive rats.

    PubMed

    Fortepiani, Lourdes A; Zhang, Huimin; Racusen, Lorraine; Roberts, L Jackson; Reckelhoff, Jane F

    2003-03-01

    Blood pressure (BP) increases in postmenopausal women. The mechanisms responsible are unknown. The present study was performed to characterize a model of postmenopausal hypertension in the rat and to determine the role that oxidative stress may play in mediating the postmenopausal hypertension. Spontaneously hypertensive rats were ovariectomized (ovx) or left intact (PMR) at 8 months and were aged to 18 months. These animals were compared with young females (YF; 4 or 8 months of age) and old males (18 months) for some measurements. Estradiol levels were decreased in PMR rats to levels not different from YF rats in proestrous or from old males. BP increased progressively with age in PMR rats but not in ovx or male rats, such that the gender difference in hypertension disappeared by 18 months. Glomerular filtration rate was lower in ovx and PMR rats than in YF rats. Renal plasma flow and renal vascular resistance were similar between YF and ovx rats, but lower and higher, respectively, in PMR rats. Serum testosterone increased by 60% in ovx rats and 400% in PMR rats compared with YF rats. Plasma renin activity also increased in PMR rats but not in ovx rats. Chronic treatment (for 8 months beginning at 8 months of age) of PMR rats with vitamins E and C, but not tempol, resulted in a significant reduction in BP and excretion of F2-isoprostanes. In contrast, tempol, but not vitamins E and C, reduced BP in old males. These data suggest that the PMR rats, but not ovx rats, may be a suitable model for the study of postmenopausal hypertension, and that oxidative stress plays a role in the increased BP.

  10. CT findings in ulcerative, granulomatous, and indeterminate colitis

    SciTech Connect

    Gore, R.M.; Marn, C.S.; Kirby, D.F.; Vogelzang, R.L.; Neiman, H.L.

    1984-08-01

    Eight patients with ulcerative colitis, three with colitis indeterminate, and 15 patients with Crohn disease were studied by computed tomography (CT) to establish CT criteria for each disorder in hopes of providing a new diagnostic perspective useful in the radiographic evaluation of inflammatory colitis. The CT findings in ulcerative colitis included thickening of the colon wall, which was characterized by inhomogeneous attenuation and a target appearance of the rectum, and proliferation of perirectal fat. Bowel wall thickening with homogeneous attenuation, fistula and abscess formation, and mesenteric abnormalities were observed in patients with Crohn colitis. Patients with colitis indeterminate showed colonic changes on CT observed in both disorders. Initial experience suggests that CT can differentiate patients with well established ulcerative and Crohn colitis.

  11. Drug therapy for ulcerative colitis

    PubMed Central

    Xu, Chang-Tai; Meng, Shu-Yong; Pan, Bo-Rong

    2004-01-01

    Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. Drug therapy is not the only choice for UC treatment and medical management should be as a comprehensive whole. Azulfidine, Asacol, Pentasa, Dipentum, and Rowasa all contain 5-aminosalicylic acid (5-ASA), which is the topical anti-inflammatory ingredient. Pentasa is more commonly used in treating Crohn’s ileitis because Pentasa capsules release more 5-ASA into the small intestine than Asacol tablets. Pentasa can also be used for treating mild to moderate UC. Rowasa enemas are safe and effective in treating ulcerative proctitis and proctosigmoiditis. The sulfa-free 5-ASA agents (Asacol, Pentasa, Dipentum and Rowasa) have fewer side effects than sulfa-containing Azulfidine. In UC patients with moderate to severe disease and in patients who failed to respond to 5-ASA compounds, systemic (oral) corticosteroids should be used. Systemic corticosteroids (prednisone, prednisolone, cortisone, etc.) are potent and fast-acting drugs for treating UC, Crohn’s ileitis and ileocolitis. Systemic corticosteroids are not effective in maintaining remission in patients with UC. Serious side effects can result from prolonged corticosteroid treatment. To minimize side effects, corticosteroids should be gradually reduced as soon as the disease remission is achieved. In patients with corticosteroid-dependent or unresponsive to corticosteroid treatment, surgery or immunomodulator is considered. Immunomodulators used for treating severe UC include azathioprine/6-MP, methotrexate, and cyclosporine. Integrated traditional Chinese and Western medicine is safe and effective in maintaining remission in patients with UC. PMID:15285010

  12. Modeling the mechanical properties of liver fibrosis in rats.

    PubMed

    Zhu, Ying; Chen, Xin; Zhang, Xinyu; Chen, Siping; Shen, Yuanyuan; Song, Liang

    2016-06-14

    The progression of liver fibrosis changes the biomechanical properties of liver tissue. This study characterized and compared different liver fibrosis stages in rats in terms of viscoelasticity. Three viscoelastic models, the Voigt, Maxwell, and Zener models, were applied to experimental data from rheometer tests and then the elasticity and viscosity were estimated for each fibrosis stage. The study found that both elasticity and viscosity are correlated with the various stages of liver fibrosis. The study revealed that the Zener model is the optimal model for describing the mechanical properties of each fibrosis stage, but there is no significant difference between the Zener and Voigt models in their performance on liver fibrosis staging. Therefore the Voigt model can still be effectively used for liver fibrosis grading. PMID:27017300

  13. Rodent models in neuroscience research: is it a rat race?

    PubMed Central

    2016-01-01

    ABSTRACT Rodents (especially Mus musculus and Rattus norvegicus) have been the most widely used models in biomedical research for many years. A notable shift has taken place over the last two decades, with mice taking a more and more prominent role in biomedical science compared to rats. This shift was primarily instigated by the availability of a much larger genetic toolbox for mice, particularly embryonic-stem-cell-based targeting technology for gene disruption. With the recent emergence of tools for altering the rat genome, notably genome-editing technologies, the technological gap between the two organisms is closing, and it is becoming more important to consider the physiological, anatomical, biochemical and pharmacological differences between rats and mice when choosing the right model system for a specific biological question. The aim of this short review and accompanying poster is to highlight some of the most important differences, and to discuss their impact on studies of human diseases, with a special focus on neuropsychiatric disorders. PMID:27736744

  14. Stem cell therapy in intracerebral hemorrhage rat model

    PubMed Central

    Cordeiro, Marcos F; Horn, Ana P

    2015-01-01

    Intracerebral hemorrhage (ICH) is a very complex pathology, with many different not fully elucidated etiologies and prognostics. It is the most severe subtype of stroke, with high mortality and morbidity rates. Unfortunately, despite the numerous promising preclinical assays including neuroprotective, anti-hypertensive, and anti-inflammatory drugs, to this moment only symptomatic treatments are available, motivating the search for new alternatives. In this context, stem cell therapy emerged as a promising tool. However, more than a decade has passed, and there is still much to be learned not only about stem cells, but also about ICH itself, and how these two pieces come together. To date, rats have been the most widely used animal model in this research field, and there is much more to be learned from and about them. In this review, we first summarize ICH epidemiology, risk factors, and pathophysiology. We then present different methods utilized to induce ICH in rats, and examine how accurately they represent the human disease. Next, we discuss the different types of stem cells used in previous ICH studies, also taking into account the tested transplantation sites. Finally, we summarize what has been achieved in assays with stem cells in rat models of ICH, and point out some relevant issues where attention must be given in future efforts. PMID:25914768

  15. Respiratory deficits in a rat model of Parkinson's disease.

    PubMed

    Tuppy, M; Barna, B F; Alves-Dos-Santos, L; Britto, L R G; Chiavegatto, S; Moreira, T S; Takakura, A C

    2015-06-25

    Parkinson's disease (PD) is a neurodegenerative disease characterized by loss of the dopaminergic nigrostriatal pathway. In addition to deficits in voluntary movement, PD involves a disturbance of breathing regulation. However, the cause and nature of this disturbance are not well understood. Here, we investigated breathing at rest and in response to hypercapnia (7% CO2) or hypoxia (8% O2), as well as neuroanatomical changes in brainstem regions essential for breathing, in a 6-hydroxydopamine (6-OHDA) rat model of PD. Bilateral injections of 6-OHDA (24μg/μl) into the striatum decreased tyrosine hydroxylase (TH(+))-neurons in the substantia nigra pars compacta (SNpc), transcription factor phox2b-expressing neurons in the retrotrapezoid nucleus and neurokinin-1 receptors in the ventral respiratory column. In 6-OHDA-lesioned rats, respiratory rate was reduced at rest, leading to a reduction in minute ventilation. These animals also showed a reduction in the tachypneic response to hypercapnia, but not to hypoxia challenge. These results suggest that the degeneration of TH(+) neurons in the SNpc leads to impairment of breathing at rest and in hypercapnic conditions. Our data indicate that respiratory deficits in a 6-OHDA rat model of PD are related to downregulation of neural systems involved in respiratory rhythm generation. The present study suggests a new avenue to better understand the respiratory deficits observed in chronic stages of PD.

  16. Achilles tendinosis – a morphometrical study in a rat model

    PubMed Central

    Silva, Rafael Duarte; Glazebrook, Mark Anthony; Campos, Vinicius Castro; Vasconcelos, Anilton Cesar

    2011-01-01

    This study addresses the morphopathogenesis of Achilles tendinosis, using a rat model and presenting quantitative analysis of time-dependent histological changes. Thirty Wistar rats were used, randomly split in experimental and control groups. Animals of the experimental group were submitted to a treadmill running scheme. Five animals of each group were euthanized at four, eight and sixteen weeks. Achilles tendons were collected and processed routinely for histopath sections. Slides were stained by Hematoxylin-Eosin, Picrosirius Red, Alcian Blue, AgNOR, TUNEL and evaluated morphometrically. Cellular density decreased slightly along the time and was higher in the experimental group than in controls at fourth, eighth and sixteenth weeks. Fiber microtearing, percentual of reticular fibers and glycosaminoglycans content increased along the time and were higher in experimental group than in controls at all-time intervals. AgNOR labeling here interpreted as a marker of transcription activity was higher in the experimental groups than in controls at all-time intervals. Apoptotic cells were more frequent and diffusely distributed in tendinosis samples than in control groups. These results suggest that as mechanical overload is becoming chronic, cellular turnover and matrix deposition increases leading to tendinosis. The combination of staining techniques and morphometry used here to describe the evolution of lesions occurring in a rat model system has proved to be suited for the study of induced Achilles tendinosis. PMID:22076169

  17. Repeated predictable stress causes resilience against colitis-induced behavioral changes in mice

    PubMed Central

    Hassan, Ahmed M.; Jain, Piyush; Reichmann, Florian; Mayerhofer, Raphaela; Farzi, Aitak; Schuligoi, Rufina; Holzer, Peter

    2014-01-01

    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 SI 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. PMID:25414650

  18. Pharmacokinetic/Pharmacodynamic Modeling of GLP-1 in Healthy Rats

    PubMed Central

    Cao, Yanguang; Gao, Wei

    2012-01-01

    Purpose To provide a mechanism-based model to quantitatively describe GLP-1 pharmacokinetics (PK) and pharmacodynamics (PD) in rats. Methods Intravenous (IV), infusion (IF), subcutaneous (SC), and intraperitoneal (IP) doses of GLP-1 were administered after glucose challenge in healthy Sprague–Dawley rats. Blood was analyzed for GLP-1, glucose, and insulin. The PK-PD modeling was performed with ADAPT 5. The concentration-response curve was generated and analyzed in comparison with other incretin-related therapeutics. Results The PK of GLP-1 was described using a two-compartment model with a zero-order input accounting for endogenous GLP-1 synthesis. For SC and IP dosing, sequential zero-order and first-order absorption models reasonably described the rapid absorption process and flip-flop kinetics. In dynamics, GLP-1 showed insulinotropic effects (3-fold increase) after IV glucose challenge in a dose-dependent manner. The concentration-response curve was bell-shaped, which was captured using a biphasic two-binding site Adair model. Receptor binding of GLP-1 exhibited high capacity and low affinity kinetics for both binding sites (KD=09.94×103 pM, K2=1.56×10−4 pM−1). Conclusions The PK of GLP-1 was linear and bi-exponential and its PD showed glucose-dependent insulinotropic effects. All profiles were captured by the present mechanistic model and the dynamic analysis yields several implications for incretin-related therapies. PMID:22179928

  19. Preventive use of Lactobacillus plantarum LS/07 and inulin to relieve symptoms of acute colitis.

    PubMed

    Hijová, Emília; Šoltésová, Alena; Salaj, Rastislav; Kuzma, Jozef; Strojný, Ladislav; Bomba, Alojz; Gregová, Kristína

    2015-01-01

    The aim of presented study was to investigate the influence of Lactobacillus plantarum LS/07 and inulin on the activity of β-glucuronidase enzyme, and counts of coliform and lactobacilli in fresh caecal digesta, cytokine levels (IL-6, IL-8), and trancription nuclear factor kappa beta (NFκB) activities in colon tissue and blood samples of rats with dextran sulphate sodium (DSS) induced acute colitis. The rats were randomly divided into four groups - CG, AC, AC+PRE and AC+PRO. Colitis was induced using of 5% DSS in drinking water for 7d. DSS application increased activity of β-glucuronidase (P < 0.001), increased counts of coliforms, and decreased lactobacilli counts (P < 0.05) in comparison to control group. Serum and tissue levels of IL-6 and IL-8 as well as tissue NFκB activities showed increased expression in acute colitis group. Inulin diet modified counts of microorganims and decreased β-glucuronidase activity, suppressed NFκB activities (P < 0.001) and down regulate synthesis of IL-6 (P < 0.01) in serum and colon tissue and tissue IL-8 (P < 0.05). Lactobacillus plantarum LS/07 decreased β-glucuronidase activity (P < 0.05), levels of IL-6 and IL-8 (P < 0.001). These results were consistent with the addition of histological findings. Our results indicate that dietary intake of Lactobacillus plantarum LS/07 and inulin suppressed expression observed markers, which play an important role in the inflammatory process, which predisposes their use in prevention or treatment of acute colitis.

  20. In vivo photoacoustic imaging of osteosarcoma in a rat model

    NASA Astrophysics Data System (ADS)

    Hu, Jun; Yu, Menglei; Ye, Fei; Xing, Da

    2011-02-01

    Osteosarcoma is one of the most common primary malignant tumors of the bone and the second leading cause of cancer-related deaths in the pediatric age group. Confirmed diagnosis and prompt treatment of osteosarcoma are critical for effective prognosis. In this study, we investigate the application of photoacoustic imaging (PAI) for the detection of osteosarcoma in an animal model. Cross-section images of a normal rat leg and a tumorous rat leg were successfully reconstructed in vivo. Morphological changes and the development of the implanted osteosarcoma were accurately mapped with time-dependent photoacoustic images. Furthermore, we evaluate the use of gold nanorods as contrast agents for imaging osteosarcoma with PAI. This is the first study that uses PAI to detect osteosarcoma in vivo, and the results suggest that PAI has the potential clinical application for detecting osteosarcoma in the early stage.

  1. Efficacy of Female Rat Models in Translational Cardiovascular Aging Research

    PubMed Central

    Rice, K. M.; Fannin, J. C.; Gillette, C.; Blough, E. R.

    2014-01-01

    Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. This review addresses the systemic pathophysiology of the cardiovascular system associated with aging and gender for aging research with regard to the applicability of rat derived data for translational application to human aging. PMID:25610649

  2. Heligmosomoides induces tolerogenic dendritic cells that block colitis and prevent antigen-specific gut Tcell responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Immunological diseases like inflammatory bowel disease (IBD) are infrequent in less developed countries possibly because helminths provide protection by modulating host immunity. In IBD murine models, the helminth Heligmosomoides bakeri (Hb) prevents colitis. It was determined if Hb mediated IBD pro...

  3. Helogmosomoides polygyrus infection can inhibit colitis through direct interaction with innate immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Less developed countries have a low incidence of immunological diseases like inflammatory bowel disease (IBD), perhaps prevented by the high prevalence of helminth infections in their populations. In the Rag IL10-/- T cell transfer model of colitis, Heligmosomoides polygyrus (Hp), an intestinal hel...

  4. The elusive rat model of conditioned placebo analgesia.

    PubMed

    McNabb, Christopher T; White, Michelle M; Harris, Amber L; Fuchs, Perry N

    2014-10-01

    Recent research on human placebo analgesia has suggested the need for rodent models to further elucidate the neural substrates of the placebo effect. This series of 3 experiments therefore was performed in an attempt to develop a model of placebo analgesia in rats. In each study, female Sprague-Dawley rats received an L5 spinal nerve ligation to induce a neuropathic pain condition. Each rat then underwent a 4-day conditioning procedure in which an active analgesic drug or its vehicle (unconditioned stimulus) was associated with the following cues (conditioned stimuli): novel testing room (environmental), vanilla scent cue (olfactory), dim incandescent lighting (visual), restraint procedure/injection (tactile), and time of day and injection-test latency (temporal). The analgesics for each experiment were as follows: Experiment 1 used 90 mg/kg gabapentin, experiment 2 used 3mg/kg loperamide hydrochloride, and experiment 3 used 6 mg/kg morphine sulfate. On the following test day, half of the animals received the opposite treatment, resulting in 4 conditioning manipulations: drug/drug, drug/vehicle, vehicle/drug, and vehicle/vehicle. Nociceptive thresholds were assessed with the mechanical paw withdrawal threshold test each day after the conditioning procedure. In all 3 experiments, no significant differences were detected on test day between control and placebo groups, indicating a lack of a conditioned placebo analgesic response. Our results contrast with prior research that implies the existence of a reliable and robust response to placebo treatment. We conclude that placebo analgesia in rats is not particularly robust and that it is difficult to achieve using conventional procedures and proper experimental design. PMID:25026214

  5. Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system

    PubMed Central

    Wang, K; Xu, R; Snider, A J; Schrandt, J; Li, Y; Bialkowska, A B; Li, M; Zhou, J; Hannun, Y A; Obeid, L M; Yang, V W; Mao, C

    2016-01-01

    Increasing studies suggest that ceramides differing in acyl chain length and/or degree of unsaturation have distinct roles in mediating biological responses. However, still much remains unclear about regulation and role of distinct ceramide species in the immune response. Here, we demonstrate that alkaline ceramidase 3 (Acer3) mediates the immune response by regulating the levels of C18:1-ceramide in cells of the innate immune system and that Acer3 deficiency aggravates colitis in a murine model by augmenting the expression of pro-inflammatory cytokines in myeloid and colonic epithelial cells (CECs). According to the NCBI Gene Expression Omnibus (GEO) database, ACER3 is downregulated in immune cells in response to lipopolysaccharides (LPS), a potent inducer of the innate immune response. Consistent with these data, we demonstrated that LPS downregulated both Acer3 mRNA levels and its enzymatic activity while elevating C18:1-ceramide, a substrate of Acer3, in murine immune cells or CECs. Knocking out Acer3 enhanced the elevation of C18:1-ceramide and the expression of pro-inflammatory cytokines in immune cells and CECs in response to LPS challenge. Similar to Acer3 knockout, treatment with C18:1-ceramide, but not C18:0-ceramide, potentiated LPS-induced expression of pro-inflammatory cytokines in immune cells. In the mouse model of dextran sulfate sodium-induced colitis, Acer3 deficiency augmented colitis-associated elevation of colonic C18:1-ceramide and pro-inflammatory cytokines. Acer3 deficiency aggravated diarrhea, rectal bleeding, weight loss and mortality. Pathological analyses revealed that Acer3 deficiency augmented colonic shortening, immune cell infiltration, colonic epithelial damage and systemic inflammation. Acer3 deficiency also aggravated colonic dysplasia in a mouse model of colitis-associated colorectal cancer. Taken together, these results suggest that Acer3 has an important anti-inflammatory role by suppressing cellular or tissue C18:1-ceramide, a

  6. Studies on sensitivity of zebrafish as a model organism for Parkinson's disease: Comparison with rat model

    PubMed Central

    Makhija, Dinesh T.; Jagtap, Aarti G.

    2014-01-01

    Objective: To determine the utility of zebra fish as an animal model for Parkinson's disease (PD) in comparison with rat model. Materials and Methods: MTT assay was performed on rat and zebrafish brain synaptosomal fractions using rotenone as a neurotoxic agent. Quercetin and resveratrol were used as standards to compare anti-apoptotic activity in both organisms. Catalepsy was induced in zebrafish by exposing them to haloperidol (9 μM) solution. Drug-treated groups were exposed to bromocriptine and pramipexole, 30 min prior to haloperidol exposure at the dose of 2, 5, and 10 μg/mL. Swimming speed, time spent in the bottom of the tank, and complete cataleptic time were evaluated to assess behavioral changes. In rats, catalepsy was induced using haloperidol (1.25 mg/kg i.p.). Drug-treated groups received bromocriptine (2.5 mg/kg.) and pramipexole (1 mg/kg) orally. Bar test, block test, and locomotor activity were carried out to assess behavioral changes. Results: Resveratrol and quercetin showed comparable inhibition of apoptosis in rats and zebrafish. In anti-cataleptic study, bromocriptine and pramipexole-treated groups showed significant difference (P < 0.05) in behavioral parameters as compared to haloperidol control group in both the experimental organisms. Results obtained from fish model were in correlation with rat model. Conclusion: Findings of the present study revealed that zebrafish model is highly sensitive and can be used for basic screening of drugs against PD. PMID:24554909

  7. Generation of a New Model Rat: Nrf2 Knockout Rats Are Sensitive to Aflatoxin B1 Toxicity.

    PubMed

    Taguchi, Keiko; Takaku, Misaki; Egner, Patricia A; Morita, Masanobu; Kaneko, Takehito; Mashimo, Tomoji; Kensler, Thomas W; Yamamoto, Masayuki

    2016-07-01

    THE TRANSCRIPTION FACTOR NRF2: (NF-E2-related-factor 2) REGULATES A BATTERY OF ANTIOXIDATIVE STRESS-RESPONSE GENES AND DETOXICATION GENES, AND NRF2 KNOCKOUT LINES OF MICE HAVE BEEN CONTRIBUTING CRITICALLY TO THE CLARIFICATION OF ROLES THAT NRF2 PLAYS FOR CELL PROTECTION HOWEVER, THERE ARE APPARENT LIMITATIONS IN USE OF THE MOUSE MODELS FOR INSTANCE, RATS EXHIBIT MORE SUITABLE FEATURES FOR TOXICOLOGICAL OR PHYSIOLOGICAL EXAMINATIONS THAN MICE IN THIS STUDY, WE GENERATED 2 LINES OF NRF2 KNOCKOUT RATS BY USING A GENOME EDITING TECHNOLOGY; 1 LINE HARBORS A 7-BP DELETION Δ7 AND THE OTHER LINE HARBORS A 1-BP INSERTION +1 IN THE NRF2 GENE IN THE LIVERS OF RATS HOMOZYGOUSLY DELETING THE NRF2 GENE, AN ACTIVATOR OF NRF2 SIGNALING, CDDO-IM, COULD NOT INDUCE EXPRESSION OF REPRESENTATIVE NRF2 TARGET GENES TO EXAMINE ALTERED TOXICOLOGICAL RESPONSE, WE TREATED THE NRF2 KNOCKOUT RATS WITH AFLATOXIN B1 AFB1, A CARCINOGENIC MYCOTOXIN THAT ELICITS GENE MUTATIONS THROUGH BINDING OF ITS METABOLITES TO DNA AND FOR WHICH THE RAT HAS BEEN PROPOSED AS A REASONABLE SURROGATE FOR HUMAN TOXICITY INDEED, IN THE NRF2 KNOCKOUT RAT LIVERS THE ENZYMES OF THE AFB1 DETOXICATION PATHWAY WERE SIGNIFICANTLY DOWNREGULATED SINGLE DOSE ADMINISTRATION OF AFB1 INCREASED HEPATOTOXICITY AND BINDING OF AFB1-N7-GUANINE TO HEPATIC DNA IN NRF2 KNOCKOUT RATS COMPARED WITH WILD-TYPE NRF2 KNOCKOUT RATS REPEATEDLY TREATED WITH AFB1 WERE PRONE TO LETHALITY AND CDDO-IM WAS NO LONGER PROTECTIVE THESE RESULTS DEMONSTRATE THAT NRF2 KNOCKOUT RATS ARE QUITE SENSITIVE TO AFB1 TOXICITIES AND THIS RAT GENOTYPE EMERGES AS A NEW MODEL ANIMAL IN TOXICOLOGY.

  8. Rectal mucocoele following subtotal colectomy for colitis.

    PubMed

    Appleton, N; Day, N; Walsh, C

    2014-09-01

    We present a unique case of a rectal mucocoele affecting a patient several years after his subtotal colectomy for ulcerative colitis. This was secondary to both a benign anorectal stenosis and a benign mucus secreting rectal adenoma. This case highlights the importance of surveillance in such patients.

  9. Ulcerative colitis flare with splenic ven thrombosis.

    PubMed

    Bozkurt, Huseyin Sancar; Kara, Banu; Citil, Serdal

    2015-01-01

    Patients with ulcerative colitis (UC) have an increased risk of thromboembolic events. Here, we present a 28-year-old man with active ulcerative pancolitis presenting via splenic vein thrombosis and left renal superior infarct that was not associated with a surgical procedure.

  10. Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission

    PubMed Central

    Rooks, Michelle G; Veiga, Patrick; Wardwell-Scott, Leslie H; Tickle, Timothy; Segata, Nicola; Michaud, Monia; Gallini, Carey Ann; Beal, Chloé; van Hylckama-Vlieg, Johan ET; Ballal, Sonia A; Morgan, Xochitl C; Glickman, Jonathan N; Gevers, Dirk; Huttenhower, Curtis; Garrett, Wendy S

    2014-01-01

    Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive multiple treatments during disease flares, confounding such analyses. Preclinical models of IBD with well-defined disease courses and opportunities for controlled treatment exposures provide a valuable solution. Here, we surveyed the gut microbiome of the T-bet−/− Rag2−/− mouse model of colitis during active disease and treatment-induced remission. Microbial features modified among these conditions included altered potential for carbohydrate and energy metabolism and bacterial pathogenesis, specifically cell motility and signal transduction pathways. We also observed an increased capacity for xenobiotics metabolism, including benzoate degradation, a pathway linking host adrenergic stress with enhanced bacterial virulence, and found decreased levels of fecal dopamine in active colitis. When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. Thus, our study provides insight into specific microbial clades and pathways associated with health, active disease and treatment interventions in a mouse model of colitis. PMID:24500617

  11. Highly specific blockade of CCR5 inhibits leukocyte trafficking and reduces mucosal inflammation in murine colitis

    PubMed Central

    Mencarelli, Andrea; Cipriani, Sabrina; Francisci, Daniela; Santucci, Luca; Baldelli, Franco; Distrutti, Eleonora; Fiorucci, Stefano

    2016-01-01

    Targeted disruption of leukocyte trafficking to the gut represents a promising approach for the treatment of inflammatory bowel diseases (IBDs). CCR5, the shared receptor for MIP1α and β and RANTES, is expressed by multiple leukocytes. Here, we aimed to determine the role of CCR5 in mediating leukocyte trafficking in models of colitis, and evaluate the therapeutic potential of maraviroc, an orally active CCR5 antagonist used in the treatment of CCR5-tropic HIV. Acute and chronic colitis were induced by administration of DSS or TNBS to wild-type and CCR5−/− mice or adoptive transfer of splenic naïve CD4+ T-cells from wild type or CCR5−/− mice into RAG-1−/−. CCR5 gene ablation reduced the mucosal recruitment and activation of CCR5-bearing CD4+ and CD11b+ leukocytes, resulting in profound attenuation of signs and symptoms of inflammation in the TNBS and transfer models of colitis. In the DSS/TNBS colitis and in the transfer model, maraviroc attenuated development of intestinal inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes. In summary, CCR5 regulates recruitment of blood leukocytes into the colon indicating that targeting CCR5 may offer therapeutic options in IBDs. PMID:27492684

  12. Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission.

    PubMed

    Rooks, Michelle G; Veiga, Patrick; Wardwell-Scott, Leslie H; Tickle, Timothy; Segata, Nicola; Michaud, Monia; Gallini, Carey Ann; Beal, Chloé; van Hylckama-Vlieg, Johan E T; Ballal, Sonia A; Morgan, Xochitl C; Glickman, Jonathan N; Gevers, Dirk; Huttenhower, Curtis; Garrett, Wendy S

    2014-07-01

    Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive multiple treatments during disease flares, confounding such analyses. Preclinical models of IBD with well-defined disease courses and opportunities for controlled treatment exposures provide a valuable solution. Here, we surveyed the gut microbiome of the T-bet(-/-) Rag2(-/-) mouse model of colitis during active disease and treatment-induced remission. Microbial features modified among these conditions included altered potential for carbohydrate and energy metabolism and bacterial pathogenesis, specifically cell motility and signal transduction pathways. We also observed an increased capacity for xenobiotics metabolism, including benzoate degradation, a pathway linking host adrenergic stress with enhanced bacterial virulence, and found decreased levels of fecal dopamine in active colitis. When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. Thus, our study provides insight into specific microbial clades and pathways associated with health, active disease and treatment interventions in a mouse model of colitis.

  13. Highly specific blockade of CCR5 inhibits leukocyte trafficking and reduces mucosal inflammation in murine colitis.

    PubMed

    Mencarelli, Andrea; Cipriani, Sabrina; Francisci, Daniela; Santucci, Luca; Baldelli, Franco; Distrutti, Eleonora; Fiorucci, Stefano

    2016-08-05

    Targeted disruption of leukocyte trafficking to the gut represents a promising approach for the treatment of inflammatory bowel diseases (IBDs). CCR5, the shared receptor for MIP1α and β and RANTES, is expressed by multiple leukocytes. Here, we aimed to determine the role of CCR5 in mediating leukocyte trafficking in models of colitis, and evaluate the therapeutic potential of maraviroc, an orally active CCR5 antagonist used in the treatment of CCR5-tropic HIV. Acute and chronic colitis were induced by administration of DSS or TNBS to wild-type and CCR5(-/-) mice or adoptive transfer of splenic naïve CD4(+) T-cells from wild type or CCR5(-/-) mice into RAG-1(-/-). CCR5 gene ablation reduced the mucosal recruitment and activation of CCR5-bearing CD4(+) and CD11b(+) leukocytes, resulting in profound attenuation of signs and symptoms of inflammation in the TNBS and transfer models of colitis. In the DSS/TNBS colitis and in the transfer model, maraviroc attenuated development of intestinal inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes. In summary, CCR5 regulates recruitment of blood leukocytes into the colon indicating that targeting CCR5 may offer therapeutic options in IBDs.

  14. Involvement of stimulation of α7 nicotinic acetylcholine receptors in the suppressive effect of tropisetron on dextran sulfate sodium-induced colitis in mice.

    PubMed

    Tasaka, Yuichi; Yasunaga, Daiki; Kiyoi, Takeshi; Tanaka, Mamoru; Tanaka, Akihiro; Suemaru, Katsuya; Araki, Hiroaki

    2015-03-01

    Ulcerative colitis (UC) involves chronic inflammation of the large intestine. Several agents are used to treat UC, but adverse side effects are remaining problems. We examined the effect of tropisetron as a new type of drug for UC using a dextran sulfate sodium (DSS)-induced model of colitis in mice. We developed a DSS-induced model of colitis and calculated the Disease Activity Index and colon length. We measured myeloperoxidase activity and determined the protein level and mRNA level of cytokines in the colon. DSS-induced colitis was ameliorated by administration of tropisetron and PNU282987. Pre-administration of methyllycaconitine diminished the suppressive effect of tropisetron upon DSS-induced colitis. These findings suggested that α7 nicotinic acetylcholine receptors (α7 nAChRs) were related to the suppressive effect of tropisetron on DSS-induced colitis. Additionally, stimulation of α7 nAChRs decreased the colon level of interleukin-6 and interferon-γ upon DSS administration. Furthermore, stimulation of α7 nAChRs decreased macrophage infiltration, with expression of α7 nAChR increased by DSS administration. These results suggest that the underlying mechanism of this suppressive effect on DSS-induced colitis is via stimulation of α7 nAChRs and involves suppression of expression of pro-inflammatory cytokines. Tropisetron could be a new type of therapeutic agent for UC.

  15. Triptolide ameliorates colonic fibrosis in an experimental rat model.

    PubMed

    Tao, Qingsong; Wang, Baochai; Zheng, Yu; Li, Guanwei; Ren, Jianan

    2015-08-01

    Triptolide is known to exert anti-inflammatory and immunomodulatory activities; however, its impact on intestinal fibrosis has not been previously examined. Based on our previous studies of the suppressive activity of triptolide on human colonic subepithelial myofibroblasts and the therapeutic efficacy of triptolide in Crohn's disease, it was hypothesized that triptolide may have beneficial effects on intestinal fibrosis. In the present study, colonic fibrosis was induced in rats by 6 weekly repeated administration with a low-dose of 2,4,6-trinitrobenzene sulfonic acid (TNBS) and was then treated with triptolide or PBS daily (control) simultaneously. Extracellular matrix (ECM) deposition in the colon was examined with image analysis of Masson Trichrome staining. Total collagen levels in colonic homogenates were measured by a Sircol assay. Collagen Iα1 transcripts and collagen I protein were measured ex vivo in the isolated colonic subepithelial myofibroblasts by reverse transcription-quantitative polymerase chain reaction and immunoblot analysis, respectively. The results indicated that triptolide decreased ECM deposition and collagen production in the colon, and inhibited collagen Iα1 transcripts and collagen I protein expression in the isolated subepithelial myofibroblasts of the rats with colonic fibrosis. In conclusion, triptolide ameliorates colonic fibrosis in the experimental rat model, suggesting triptolide may be a promising compound for inflammatory bowel disease treatment. PMID:25845760

  16. Triptolide ameliorates colonic fibrosis in an experimental rat model

    PubMed Central

    TAO, QINGSONG; WANG, BAOCHAI; ZHENG, YU; LI, GUANWEI; REN, JIANAN

    2015-01-01

    Triptolide is known to exert anti-inflammatory and immunomodulatory activities; however, its impact on intestinal fibrosis has not been previously examined. Based on our previous studies of the suppressive activity of triptolide on human colonic subepithelial myofibroblasts and the therapeutic efficacy of triptolide in Crohn’s disease, it was hypothesized that triptolide may have beneficial effects on intestinal fibrosis. In the present study, colonic fibrosis was induced in rats by 6 weekly repeated administration with a low-dose of 2,4,6-trinitrobenzene sulfonic acid (TNBS) and was then treated with triptolide or PBS daily (control) simultaneously. Extracellular matrix (ECM) deposition in the colon was examined with image analysis of Masson Trichrome staining. Total collagen levels in colonic homogenates were measured by a Sircol assay. Collagen Iα1 transcripts and collagen I protein were measured ex vivo in the isolated colonic subepithelial myofibroblasts by reverse transcription-quantitative polymerase chain reaction and immunoblot analysis, respectively. The results indicated that triptolide decreased ECM deposition and collagen production in the colon, and inhibited collagen Iα1 transcripts and collagen I protein expression in the isolated subepithelial myofibroblasts of the rats with colonic fibrosis. In conclusion, triptolide ameliorates colonic fibrosis in the experimental rat model, suggesting triptolide may be a promising compound for inflammatory bowel disease treatment. PMID:25845760

  17. Polyphosphate, an active molecule derived from probiotic Lactobacillus brevis, improves the fibrosis in murine colitis.

    PubMed

    Kashima, Shin; Fujiya, Mikihiro; Konishi, Hiroaki; Ueno, Nobuhiro; Inaba, Yuhei; Moriichi, Kentaro; Tanabe, Hiroki; Ikuta, Katsuya; Ohtake, Takaaki; Kohgo, Yutaka

    2015-08-01

    Inflammatory bowel disease frequently causes intestinal obstruction because of extensive fibrosis. This study investigated whether polyphosphate (poly P), an active molecule derived from Lactobacillus brevis, could improve the fibrosis in a model of chronic colitis. In this study, dextran sodium sulfate (DSS)-induced chronic colitis models and trinitrobenzene sulfonic acid (TNBS)-induced colitis models were used as models of fibrosis. To clarify the mechanism responsible for the observed effects, Caco-2/brush border epithelial (BBE) and naive T helper lymphocyte (THP)-1 cells were treated with lipopolysaccharide (LPS) to induce inflammation. Non-cancer human colon fibroblast (CCD-18) cells were treated with transforming growth factor beta 1 (TGF-β1) to induce fibrosis. The expression levels of fibrosis- and inflammation-associated molecules were evaluated by both a Western blotting analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). The histologic inflammation and fibrosis were significantly improved in the group administered poly P in both the DSS and TNBS colitis models. The levels of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were significantly decreased by poly P treatment. The expression levels of TGF-β1 and collagens in the colitis mice were decreased by poly P. The LPS-induced expressions of IL-1β and TGF-β1 in Caco-2/BBE cells and of TNF-α in THP-1 cells were reduced by poly P treatment. Poly P did not affect the expression of collagens and connective tissue growth factor in the CCD-18 cells. In conclusion, poly P suppresses intestinal inflammation and fibrosis by downregulating the expression of inflammation- and fibrosis-associated molecules in the intestinal epithelium. The administration of poly P is therefore a novel option to treat fibrosis because of chronic intestinal inflammation. PMID:25766132

  18. Sulfated polysaccharide from the marine algae Hypnea musciformis inhibits TNBS-induced intestinal damage in rats.

    PubMed

    V Brito, Tarcisio; Barros, Francisco C N; Silva, Renan O; Dias Júnior, Genilson J; C Júnior, José Simião; Franco, Álvaro X; Soares, Pedro M G; Chaves, Luciano S; Abreu, Clara M W S; de Paula, Regina C M; Souza, Marcellus H L P; Freitas, Ana Lúcia P; R Barbosa, André Luiz

    2016-10-20

    Sulfated polysaccharides extracted from seaweed have important pharmacological properties. Thus, the aim of this study was to characterize the sulfated polysaccharide (PLS) from the algae Hypnea musciformis and evaluate its protective effect in colitis induced by trinitrobenzene sulfonic acid in rats. The sulfated polysaccharide possess a high molecular mass (1.24×10(5)gmol(-1)) and is composed of a κ-carrageenan, as depicted by FT-IR and NMR spectroscopic data. PLS was administered orally (10, 30, and 60mg/kg, p.o.) for three days, starting before TNBS (trinitrobenzene sulfonic acid) instillation (day 1). The rats were killed on day three, the portion of distal colon (5cm) was excised and evaluated macroscopic scores and wet weight. Then, samples of the intestinal were used for histological evaluation and quantification of glutathione, malonyldialdehyde acid, myeloperoxidase, nitrate/nitrite and cytokines. Our results demonstrate that PLS reduced the colitis and all analyzed biochemical parameters. Thus, we concluded that the PLS extracted from the marine algae H. musciformis reduced the colitis in animal model and may have an important promising application in the inflammatory bowel diseases.

  19. Sulfated polysaccharide from the marine algae Hypnea musciformis inhibits TNBS-induced intestinal damage in rats.

    PubMed

    V Brito, Tarcisio; Barros, Francisco C N; Silva, Renan O; Dias Júnior, Genilson J; C Júnior, José Simião; Franco, Álvaro X; Soares, Pedro M G; Chaves, Luciano S; Abreu, Clara M W S; de Paula, Regina C M; Souza, Marcellus H L P; Freitas, Ana Lúcia P; R Barbosa, André Luiz

    2016-10-20

    Sulfated polysaccharides extracted from seaweed have important pharmacological properties. Thus, the aim of this study was to characterize the sulfated polysaccharide (PLS) from the algae Hypnea musciformis and evaluate its protective effect in colitis induced by trinitrobenzene sulfonic acid in rats. The sulfated polysaccharide possess a high molecular mass (1.24×10(5)gmol(-1)) and is composed of a κ-carrageenan, as depicted by FT-IR and NMR spectroscopic data. PLS was administered orally (10, 30, and 60mg/kg, p.o.) for three days, starting before TNBS (trinitrobenzene sulfonic acid) instillation (day 1). The rats were killed on day three, the portion of distal colon (5cm) was excised and evaluated macroscopic scores and wet weight. Then, samples of the intestinal were used for histological evaluation and quantification of glutathione, malonyldialdehyde acid, myeloperoxidase, nitrate/nitrite and cytokines. Our results demonstrate that PLS reduced the colitis and all analyzed biochemical parameters. Thus, we concluded that the PLS extracted from the marine algae H. musciformis reduced the colitis in animal model and may have an important promising application in the inflammatory bowel diseases. PMID:27474644

  20. Animal models of schizophrenia: developmental preparation in rats.

    PubMed

    Ratajczak, Piotr; Wozniak, Anna; Nowakowska, Elzbieta

    2013-01-01

    Schizophrenia manifests itself primarily with positive symptoms, negative symptoms and cognitive disorders. Animal models of mental diseases seem to be an important tool in understanding key theories related with pathophysiology of the disorder and are used to assess efficacy of new drugs. References describe four basic groups of animal models of schizophrenia, such as: models created by pharmacological intervention, genetic models, lesion models and models of developmental disorders of primary brain structures. Of the models referred to above, the group of developmental disorder models is particularly noteworthy, as they are primarily easy to use, and the methods are highly sensitive. High scientific value of these models is associated with the neurodevelopmental theory which stipulates that at an early stage of body development, a number of interactions between genetic and environmental factors may affect the development of neurons which may cause disorders of brain cytoarchitecture development. We review six developmental models of schizophrenia in rats (MAM--methylooxymethanol acetate, prenatal stress, maternal deprivation, isolation rearing, prenatal immune challenge and maternal malnutrition) that are all validated by disruption in PPI. PMID:24457639

  1. Mouse and Cotton Rat Models of Human Respiratory Syncytial Virus.

    PubMed

    Rudd, Penny A; Chen, Weiqiang; Mahalingam, Suresh

    2016-01-01

    Human respiratory syncytial virus (hRSV) is a common respiratory virus that is usually no cause for alarm. Symptoms of hRSV usually resemble those of the common cold and can go undiagnosed. However, infants as well as the elderly are at risk for developing severe cases, which can lead to high morbidity and mortality rates especially if there are underlying health issues. Despite many years of effort, no vaccine or specific treatments exist and RSV is still the leading cause of infant hospitalizations worldwide. Here, we describe methods to infect two widely used small animal models: laboratory mice and cotton rats. PMID:27464697

  2. RNase-L deficiency exacerbates experimental colitis and colitis-associated cancer

    PubMed Central

    Long, Tiha M.; ArindamChakrabarti; Ezelle, Heather J.; E. Brennan-Laun, Sarah; Raufman, Jean-Pierre; Polyakova, Irina; H. Silverman, Robert; Hassel, Bret A.

    2013-01-01

    Background The endoribonuclease RNase-L is a type-I interferon (IFN)-regulatedcomponent of the innate immune response that functions in antiviral, antibacterial and antiproliferative activities. RNase-L produces RNA agonists of RIG-I-like receptors (RLRs), sensors of cytosolic pathogen-associated RNAs that induce cytokines including IFNβ. IFNβ and RLR signaling mediate protective responses against experimental colitis and colitis-associated cancer (CAC) and contribute to gastrointestinal (GI) homeostasis. Therefore, we investigated a role for RNase-L in murine colitis and CAC and its association with RLR signaling in response to bacterial RNA. Methods Colitis was induced in wild type (WT) and RNase-L-deficient mice (RNase-L−/−) by administration of dextran sulphate sodium (DSS). CAC was induced by DSS and azoxymethane (AOM). Histological analysis and immunohistochemistry were performed on colon tissue to analyze immune cell infiltration and tissue damage following induction of colitis. Expression of cytokines was measured by qRT-PCR and ELISA. Results DSS-treated RNase-L−/− mice exhibited a significantly higher clinical score, delayed leukocyte infiltration, reduced expression of IFNβ, TNFα, IL-1β and IL-18at early times post-DSS exposure and increased mortalityas compared to WT mice. DSS/AOM-treated RNase-L−/−mice displayed an increased tumor burden. Bacterial RNA triggeredIFNβproductionin an RNase-L-dependent manner and provided a potential mechanism by whichRNase-L contributes to the GI immune response to microbiota and protects against experimental colitis and CAC. Conclusions RNase-L promotes the innate immune response to intestinal damage and ameliorates murine colitis and CAC. The RNase-L-dependent production of IFNβ stimulated by bacterial RNA may be a mechanism to protectagainst GI inflammatory disease. PMID:23567782

  3. Modeling postpartum depression in rats: theoretic and methodological issues

    PubMed Central

    Ming, LI; Shinn-Yi, CHOU

    2016-01-01

    The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions. PMID:27469254

  4. Modeling postpartum depression in rats: theoretic and methodological issues.

    PubMed

    Li, Ming; Chou, Shinn-Yi

    2016-07-18

    The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions. PMID:27469254

  5. Novel guggulsterone derivative GG-52 inhibits NF-kappaB signaling in intestinal epithelial cells and attenuates acute murine colitis.

    PubMed

    Kim, Jung Mogg; Kang, Hyoun Woo; Cha, Mi Yeon; Yoo, Doyoung; Kim, Nayoung; Kim, In-Kyoung; Ku, Jeounghun; Kim, Sunil; Ma, Sang-Ho; Jung, Hyun Chae; Song, In Sung; Kim, Joo Sung

    2010-07-01

    We already showed that the plant sterol guggulsterone has been reported to inhibit nuclear factor-kappaB (NF-kappaB) signaling in intestinal epithelial cells (IECs) and to attenuate dextran sulfate sodium (DSS)-induced colitis. This study investigates the anti-inflammatory effects of novel guggulsterone derivatives on IEC and preventive and therapeutic murine models of DSS-induced colitis. Novel guggulsterone derivates with high lipophilicity were designed and four derivates, including GG-46, GG-50B, GG-52, and GG-53, were synthesized. Two guggulsterone derivatives, GG-50B and GG-52, significantly inhibited the activated NF-kappaB signals and the upregulated expression of interleukin-8 (IL-8) in COLO 205 cells stimulated with tumor necrosis factor-alpha (TNF-alpha). Pretreatment with GG-50B and GG-52 attenuated the increased IkappaB kinase (IKK) and IkappaBalpha phsophorylation induced by TNF-alpha. In preventive and therapeutic models of murine colitis, administration of GG-52 significantly reduced the severity of DSS-induced colitis, as assessed by disease activity index, colon length, and histology. In contrast, GG-50B did not show a significant reduction in the colitis severity. Moreover, the efficacy on attenuating colitis by GG-52 was comparable to that by sulfasalazine or prednisolone. These results indicate that the novel guggulsterone derivative GG-52 blocks NF-kappaB activation in IEC and ameliorates DSS-induced acute murine colitis, which suggests that GG-52 is a potential therapeutic agent for the treatment of inflammatory bowel diseases.

  6. Disturbance in the Mucosa-Associated Commensal Bacteria Is Associated with the Exacerbation of Chronic Colitis by Repeated Psychological Stress; Is That the New Target of Probiotics?

    PubMed

    Arase, Sohei; Watanabe, Yohei; Setoyama, Hiromi; Nagaoka, Noriko; Kawai, Mitsuhisa; Matsumoto, Satoshi

    2016-01-01

    Psychological stress can exacerbate inflammatory bowel disease. However, the mechanisms underlying how psychological stress affects gut inflammation remain unclear. Here, we focused on the relationship between changes in the microbial community of mucosa-associated commensal bacteria (MACB) and mucosal immune responses induced by chronic psychological stress in a murine model of ulcerative colitis. Furthermore, we examined the effect of probiotic treatment on exacerbated colitis and MACB composition changes induced by chronic psychological stress. Repeated water avoidance stress (rWAS) in B6-Tcra-/- mice severely exacerbated colitis, which was evaluated by both colorectal tissue weight and histological score of colitis. rWAS treatment increased mRNA expression of UCN2 and IFN-γ in large intestinal lamina propria mononuclear cells (LI-LPMC). Interestingly, exacerbated colitis was associated with changes in the microbial community of MACB, specifically loss of bacterial species diversity and an increase in the component ratio of Clostridium, revealed by 16S rRNA gene amplicon analysis. Finally, the oral administration of a probiotic Lactobacillus strain was protective against the exacerbation of colitis and was associated with a change in the bacterial community of MACB in rWAS-exposed Tcra-/- mice. Taken together, these results suggested that loss of species diversity in MACB might play a key role in exacerbated colitis induced by chronic psychological stress. In addition, probiotic treatment may be used as a tool to preserve the diversity of bacterial species in MACB and alleviate gut inflammation induced by psychological stress.

  7. Phosphorylcholine-tuftsin compound prevents development of dextransulfate-sodium-salt induced murine colitis: implications for the treatment of human inflammatory bowel disease.

    PubMed

    Ben-Ami Shor, Dana; Bashi, Tomer; Lachnish, Jordan; Fridkin, Mati; Bizzaro, Giorgia; Barshak, Iris; Blank, Miri; Shoenfeld, Yehuda

    2015-01-01

    Improved clinical findings of inflammatory bowel disease (IBD) upon treatment with helminthes and their ova were proven in animal models of IBD and in human clinical studies. The immunomodulatory properties of several helminthes were attributed to the phosphorylcholine (PC) molecule. We assessed the therapeutic potential of tuftsin-PC conjugate (TPC) to attenuate murine colitis. Colitis was induced by Dextransulfate-Sodium-Salt (DSS) in drinking water. TPC was given by daily oral ingestion (50 μg/0.1 ml/mouse or PBS) starting at day -2. Disease activity index (DAI) score was followed daily and histology of the colon was performed by H&E staining. Analysis of the cytokines profile in distal colon lysates was performed by immunoblot. Treatment of DSS induced colitis with TPC prevented the severity of colitis, including a reduction in the DAI score, less shortening of the colon and less inflammatory activity in histology. The immunoblot showed that the colitis preventive activity of TPC was associated with downregulation of colon pro-inflammatory IL-1β, TNFα and IL-17 cytokines expression, and enhancement of anti-inflammatory IL-10 cytokine expression. In the current study, we demonstrated that TPC treatment can prevent significantly experimental colitis induction in naïve mice. We propose the TPC as a novel potential small synthetic molecule to treat colitis.

  8. Disturbance in the Mucosa-Associated Commensal Bacteria Is Associated with the Exacerbation of Chronic Colitis by Repeated Psychological Stress; Is That the New Target of Probiotics?

    PubMed Central

    Arase, Sohei; Watanabe, Yohei; Setoyama, Hiromi; Nagaoka, Noriko; Kawai, Mitsuhisa; Matsumoto, Satoshi

    2016-01-01

    Psychological stress can exacerbate inflammatory bowel disease. However, the mechanisms underlying how psychological stress affects gut inflammation remain unclear. Here, we focused on the relationship between changes in the microbial community of mucosa-associated commensal bacteria (MACB) and mucosal immune responses induced by chronic psychological stress in a murine model of ulcerative colitis. Furthermore, we examined the effect of probiotic treatment on exacerbated colitis and MACB composition changes induced by chronic psychological stress. Repeated water avoidance stress (rWAS) in B6-Tcra-/- mice severely exacerbated colitis, which was evaluated by both colorectal tissue weight and histological score of colitis. rWAS treatment increased mRNA expression of UCN2 and IFN-γ in large intestinal lamina propria mononuclear cells (LI-LPMC). Interestingly, exacerbated colitis was associated with changes in the microbial community of MACB, specifically loss of bacterial species diversity and an increase in the component ratio of Clostridium, revealed by 16S rRNA gene amplicon analysis. Finally, the oral administration of a probiotic Lactobacillus strain was protective against the exacerbation of colitis and was associated with a change in the bacterial community of MACB in rWAS-exposed Tcra-/- mice. Taken together, these results suggested that loss of species diversity in MACB might play a key role in exacerbated colitis induced by chronic psychological stress. In addition, probiotic treatment may be used as a tool to preserve the diversity of bacterial species in MACB and alleviate gut inflammation induced by psychological stress. PMID:27500935

  9. Na-H Exchanger Isoform-2 (NHE2) Mediates Butyrate-dependent Na+ Absorption in Dextran Sulfate Sodium (DSS)-induced Colitis.

    PubMed

    Rajendran, Vazhaikkurichi M; Nanda Kumar, Navalpur S; Tse, Chung M; Binder, Henry J

    2015-10-16

    Diarrhea associated with ulcerative colitis (UC) occurs primarily as a result of reduced Na(+) absorption. Although colonic Na(+) absorption is mediated by both epithelial Na(+) channels (ENaC) and Na-H exchangers (NHE), inhibition of NHE-mediated Na(+) absorption is the primary cause of diarrhea in UC. As there are conflicting observations reported on NHE expression in human UC, the present study was initiated to identify whether NHE isoforms (NHE2 and NHE3) expression is altered and how Na(+) absorption is regulated in DSS-induced inflammation in rat colon, a model that has been used to study UC. Western blot analyses indicate that neither NHE2 nor NHE3 expression is altered in apical membranes of inflamed colon. Na(+) fluxes measured in vitro under voltage clamp conditions in controls demonstrate that both HCO3 (-)-dependent and butyrate-dependent Na(+) absorption are inhibited by S3226 (NHE3-inhibitor), but not by HOE694 (NHE2-inhibitor) in normal animals. In contrast, in DSS-induced inflammation, butyrate-, but not HCO3 (-)-dependent Na(+) absorption is present and is inhibited by HOE694, but not by S3226. These observations indicate that in normal colon NHE3 mediates both HCO3 (-)-dependent and butyrate-dependent Na(+) absorption, whereas DSS-induced inflammation activates NHE2, which mediates butyrate-dependent (but not HCO3 (-)-dependent) Na(+) absorption. In in vivo loop studies HCO3 (-)-Ringer and butyrate-Ringer exhibit similar rates of water absorption in normal rats, whereas in DSS-induced inflammation luminal butyrate-Ringer reversed water secretion observed with HCO3 (-)-Ringer to fluid absorption. Lumen butyrate-Ringer incubation activated NHE3-mediated Na(+) absorption in DSS-induced colitis. These observations suggest that the butyrate activation of NHE2 would be a potential target to control UC-associated diarrhea.

  10. Metabolic Cages for a Space Flight Model in the Rat

    NASA Technical Reports Server (NTRS)

    Harper, Jennifer S.; Mulenburg, Gerald M.; Evans, Juli; Navidi, Meena; Wolinsky, Ira; Arnaud, Sara B.

    1994-01-01

    A variety of space flight models are available to mimic the physiologic changes seen in the rat during weightlessness. The model reported by Wronski and Morey-Holton has been widely used by many investigators, in musculoskeletal physiologic studies especially, resulting in accumulation of an extensive database that enables scientists to mimic space flight effects in the 1-g environment of Earth. However, information on nutrition or gastrointestinal and renal function in this space flight model is limited by the difficulty in acquiring uncontaminated metabolic specimens for analysis. In the Holton system, a traction tape harness is applied to the tail, and the rat's hindquarters are elevated by attaching the harness to a pulley system. Weight-bearing hind limbs are unloaded, and there is a headward fluid shift. The tail-suspended rats are able to move freely about their cages on their forelimbs and tolerate this procedure with minimal signs of stress. The cage used in Holton's model is basically a clear acrylic box set on a plastic grid floor with the pulley and tail harness system attached to the open top of the cage. Food is available from a square food cup recessed into a corner of the floor. In this system, urine, feces, and spilled food fall through the grid floor onto absorbent paper beneath the cage and cannot be separated and recovered quantitatively for analysis in metabolic balance studies. Commercially available metabolic cages are generally cylindrical and have been used with a centrally located suspension apparatus in other space flight models. The large living area, three times as large as most metabolic cages, and the free range of motion unique to Holton's model, essential for musculoskeletal investigations, were sacrificed. Holton's cages can accommodate animals ranging in weight from 70 to 600 g. Although an alternative construction of Holton's cage has been reported, it does not permit collection of separate urine and fecal samples. We describe

  11. Hypertension and vulnerability to hemorrhagic shock in a rat model.

    PubMed

    Reynolds, Penny S; Song, Kyle Seokhan; Tamariz, Francisco J; Wayne Barbee, R

    2015-02-01

    Trauma mortality may be increased in the presence of preexisting diseases such as chronic hypertension. We hypothesized that systemic and microvascular alterations accompanying chronic hypertension would increase the vulnerability to hemorrhage relative to normotensive controls in a rat model of hemorrhagic shock. We present a novel comparative hemorrhage model of shock vulnerability, quantified by "vulnerability curves" expressing physiological response to hemorrhage as a function of three matched shock metrics: cumulative blood volume, mean arterial pressure (MAP), and oxygen delivery (Do2). Responses were central hemodynamics and respiratory and muscle oxygenation obtained for one hypertensive (spontaneously hypertensive [SHR]) and two normotensive (Sprague-Dawley, Wistar-Kyoto) rat strains. Hemorrhagic shock was induced by incremental (0.5 mL) hemorrhage to cardiovascular collapse in anesthetized and mechanically ventilated animals. Shock vulnerability of SHR rats was primarily pressure-driven; in general, SHR exhibited the expected patterns of more rapid deterioration in MAP and Vo2 over smaller ranges of blood loss and Do2. Sternotomy-related depression of CO and thus Do2 in SHR meant that we could not test hypotheses related to the role of Do2 and contribution to perfusion differences between normotensive and hypertensive subjects. Insensitivity of lactate to strain effects suggests that lactate may be a reliable biomarker of shock status. Unexpected similarities between Wistar-Kyoto and SHR suggest strain-related effects other than those related to hypertension per se contribute to hemorrhage response; body size effects and genetic relationships could not be ruled out. Future studies should incorporate phylogenetically based methods to examine the role of hypertension and physiological response to hemorrhage across multiple strains.

  12. 2015 Guidelines for Establishing Genetically Modified Rat Models for Cardiovascular Research

    PubMed Central

    Flister, Michael J.; Prokop, Jeremy W.; Lazar, Jozef; Shimoyama, Mary; Dwinell, Melinda; Geurts, Aron

    2015-01-01

    The rat has long been a key physiological model for cardiovascular research; most of the inbred strains having been previously selected for susceptibility or resistance to various cardiovascular diseases (CVD). These CVD rat models offer a physiologically relevant background on which candidates of human CVD can be tested in a more clinically translatable experimental setting. However, a diverse toolbox for genetically modifying the rat genome to test molecular mechanisms has only recently become available. Here, we provide a high-level description of several strategies for developing genetically modified rat models of CVD. PMID:25920443

  13. Contemporary methods for the diagnosis and treatment of microscopic colitis.

    PubMed

    Jauregui-Amezaga, Aranzazu; Vermeire, Séverine; Geboes, Karel

    2016-01-01

    Microscopic colitis is a common cause of chronic diarrhea. It is characterized by non-bloody watery diarrhea with macroscopically normal colonic mucosa. Its specific histological characteristics confirm the diagnosis. Two distinct histological forms can be identified, namely, collagenous colitis and lymphocytic colitis. In collagenous colitis, a thick colonic subepithelial collagenous deposit can be observed, whereas in lymphocytic colitis, a pronounced intraepithelial lymphocytic inflammation in the absence of a thickened collagen band can be identified. Microscopic colitis occurs more frequently in elderly females and its etiology is believed to be multifactorial, although smoking and consumption of several drugs have been identified as risks factors for the development of the disease. The treatment is based on avoiding the risks factors and administration of oral budesonide. PMID:26470823

  14. Grape powder prevents cognitive, behavioral, and biochemical impairments in a rat model of posttraumatic stress disorder.

    PubMed

    Solanki, Naimesh; Alkadhi, Isam; Atrooz, Fatin; Patki, Gaurav; Salim, Samina

    2015-01-01

    Previously, using the single-prolonged stress (SPS) rat model of posttraumatic stress disorder, we reported that moderate treadmill exercise, via modulation of oxidative stress-related mechanisms, rescued anxiety- and depression-like behaviors and reversed SPS-induced memory impairment. In this study using the SPS model (2-hour restrain, 20-minute forced swimming, 15-minute rest, and 1-2-minute diethyl ether exposure), we hypothesized that antioxidant rich grape powder (GP) prevents SPS-induced behavioral and memory impairment in rats. Male Sprague Dawley rats were randomly assigned into control (CON) (provided tap water), SPS (provided tap water), GP-SPS (provided 15 g/L GP in tap water for 3 weeks followed by SPS), or GP-CON (3 weeks of GP followed by CON exposure). Anxiety- and depression-like behaviors were significantly greater in SPS rats, when compared with CON- or GP-treated rats, and GP reversed these behavioral deficits. Single-prolonged stress rats made significantly more errors in both short- and long-term memory tests compared with CON- or GP-treated rats, which were prevented in GP-SPS rats. Grape powder prevented SPS-induced increase in plasma corticosterone level. Furthermore, brain-derived neurotrophic factor levels were significantly decreased in amygdala of SPS rats but not in GP-SPS rats compared with CON or (GP-CON) rats. In addition, GP significantly increased acetylated histone 3 and histone deacetylase 5 in hippocampus and amygdala of SPS rats as compared with CON or GP-CON rats. In conclusion, we suggest protective role of GP in SPS-induced behavioral, cognitive, and biochemical impairments in rats. Perhaps, epigenetic regulation of brain-derived neurotrophic factor enables GP-mediated prevention of SPS-induced deficits in rats.

  15. A nitro-arginine derivative of trimebutine (NO2-Arg-Trim) attenuates pain induced by colorectal distension in conscious rats.

    PubMed

    Distrutti, Eleonora; Mencarelli, Andrea; Renga, Barbara; Caliendo, Giuseppe; Santagada, Vincenzo; Severino, Beatrice; Fiorucci, Stefano

    2009-05-01

    Irritable bowel syndrome (IBS) is characterized by dysfunction of the afferent pathways that may lead to visceral hypersensitivity. Trimebutine is a weak opioid receptor agonist used in the treatment of IBS. We report on the effects of a novel derivative in which trimebutine has been salified with nitro-arginine(NO2-Arg-Trim), in modulating nociception to colorectal distension (CRD) in intact and post-colitis rats,an animal model that mimics some features of IBS. Colorectal sensitivity and pain were assessed by measuring the abdominal withdrawal score (AWR) during CRD. Healthy rats were treated with vehicle,trimebutine (10 mg/kg i.p.) or NO2-Arg-Trim (4, 8 and 16 mg/kg i.p.). Post-colitis, allodynic rats were investigated 4 weeks after colitis induction. Treating healthy rats with NO2-Arg-Trim resulted in a dose-dependent attenuation of CRD-induced nociception and in an inhibition of CRD-induced overexpression of spinal cFOS mRNA. NO2-Arg-Trim-induced antinociception was reversed by the opioid receptor antagonist naloxone and by the NO synthase-cGMP pathway inhibitor methylene blue, while L-NAME had no effect.The antinociceptive effect of NO2-Arg-Trim was maintained in a rodent model of post-inflammatory allodynia. In this setting,NO2-Arg-Trim but not trimebutine, significantly down-regulated the spinal cFOS mRNA expression and increased blood concentrations of NO2 +NO3. Moreover, the expression of several genes involved in inflammation and pain, as IL-1beta, TNFalpha, COX2 and iNOS, was up-regulated in colonic tissue from post-colitis rats and NO2-Arg-Trim, but not trimebutine, effectively reversed this effect. In summary, these data suggest that NO2-Arg-Trim inhibits nociception induced by CRD in both healthy and post-colitis, allodynic rats. The NO2-arginine moiety interacts with the opioid agonist trimebutine to potentiate its analgesic activity. This study provides evidence that NO2-arginine derivative of trimebutine might have beneficial effect in the

  16. A Model of Insulin Resistance and Nonalcoholic Steatohepatitis in Rats

    PubMed Central

    Svegliati-Baroni, Gianluca; Candelaresi, Cinzia; Saccomanno, Stefania; Ferretti, Gianna; Bachetti, Tiziana; Marzioni, Marco; De Minicis, Samuele; Nobili, Liliana; Salzano, Renata; Omenetti, Alessia; Pacetti, Deborah; Sigmund, Soeren; Benedetti, Antonio; Casini, Alessandro

    2006-01-01

    Insulin resistance induces nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). We used a high-fat, high-calorie solid diet (HFD) to create a model of insulin resistance and NASH in nongenetically modified rats and to study the relationship between visceral adipose tissue and liver. Obesity and insulin resistance occurred in HFD rats, accompanied by a progressive increase in visceral adipose tissue tumor necrosis factor (TNF)-α mRNA and in circulating free fatty acids. HFD also decreased adiponectin mRNA and peroxisome proliferator-activated receptor (PPAR)-α expression in the visceral adipose tissue and the liver, respectively, and induced hepatic insulin resistance through TNF-α-mediated c-Jun N-terminal kinase (JNK)-dependent insulin receptor substrate-1Ser307 phosphorylation. These modifications lead to hepatic steatosis accompanied by oxidative stress phenomena, necroinflammation, and hepatocyte apoptosis at 4 weeks and by pericentral fibrosis at 6 months. Supplementation of n-3 polyunsaturated fatty acid, a PPARα ligand, to HFD-treated animals restored hepatic adiponectin and PPARα expression, reduced TNF-α hepatic levels, and ameliorated fatty liver and the degree of liver injury. Thus, our model mimics the most common features of NASH in humans and provides an ideal tool to study the role of individual pathogenetic events (as for PPARα down-regulation) and to define any future experimental therapy, such as n-3 polyunsaturated fatty acid, which ameliorated the degree of liver injury. PMID:16936261

  17. Cytomegalovirus-associated colitis causing diarrhea in an immunocompetent patient

    PubMed Central

    Carter, Dan; Olchovsky, David; Pokroy, Russell; Ezra, David

    2006-01-01

    Cytomegalovirus (CMV) colitis rarely occurs in immunocompetent patients. We report a case of disabling and life threatening diarrhea in an immunocompetent elderly woman due to CMV colitis. The diagnosis of CMV was based on histological examination of tissues biopsied at colonoscopy, positive CMV antigen and high CMV-IgM titer in peripheral blood samples and a good response to systemic gancyclovir treatment. We conclude that CMV should be considered in the differential diagnosis of colitis in elderly immunocompetent patients. PMID:17106945

  18. Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

    PubMed Central

    Khajah, Maitham A.; Fateel, Maryam M.; Ananthalakshmi, Kethireddy V.; Luqmani, Yunus A.

    2016-01-01

    Background There is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study. Methods The colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model. Results Enhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1–7 treatment (0.01–0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1–7 treatment. Conclusion Our results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression. PMID:26963721

  19. Elucidating the gut microbiome of ulcerative colitis: bifidobacteria as novel microbial biomarkers.

    PubMed

    Duranti, Sabrina; Gaiani, Federica; Mancabelli, Leonardo; Milani, Christian; Grandi, Andrea; Bolchi, Angelo; Santoni, Andrea; Lugli, Gabriele Andrea; Ferrario, Chiara; Mangifesta, Marta; Viappiani, Alice; Bertoni, Simona; Vivo, Valentina; Serafini, Fausta; Barbaro, Maria Raffaella; Fugazza, Alessandro; Barbara, Giovanni; Gioiosa, Laura; Palanza, Paola; Cantoni, Anna Maria; de'Angelis, Gian Luigi; Barocelli, Elisabetta; de'Angelis, Nicola; van Sinderen, Douwe; Ventura, Marco; Turroni, Francesca

    2016-12-01

    Ulcerative colitis (UC) is associated with a substantial alteration of specific gut commensals, some of which may be involved in microbiota-mediated protection. In this study, microbiota cataloging of UC patients by 16S rRNA microbial profiling revealed a marked reduction of bifidobacteria, in particular the Bifidobacterium bifidum species, thus suggesting that this taxon plays a biological role in the aetiology of UC. We investigated this further through an in vivo trial by testing the effects of oral treatment with B. bifidum PRL2010 in a wild-type murine colitis model. TNBS-treated mice receiving 10(9) cells of B. bifidum PRL2010 showed a marked reduction of all colitis-associated histological indices as well as maintenance of mucosal integrity as it was shown by the increase in the expression of many tight junction-encoding genes. The protective role of B. bifidum PRL2010, as well as its sortase-dependent pili, appears to be established through the induction of an innate immune response of the host. These results highlight the importance of B. bifidum as a microbial biomarker for UC, revealing its role in protection against experimentally induced colitis. PMID:27604252

  20. Brugia malayi abundant larval transcript 2 protein treatment attenuates experimentally-induced colitis in mice.

    PubMed

    Khatri, Vishal; Amdare, Nitin; Yadav, Ravi Shankar; Tarnekar, Aaditya; Goswami, Kalyan; Reddy, Maryada Venkata Rami

    2015-11-01

    Helminths are known to modulate host's immunity by suppressing host protective pro-inflammatory responses. Such immunomodulatory effects have been experimentally shown to have therapeutic implications in immune mediated disorders. In the present study, we have explored a filarial protein i.e. Brugia malayi recombinant abundant larval transcript 2 (rBmALT2) for its therapeutic effect in dextran sodium sulfate (DSS) induced colitis in mouse model. The immunomodulatory activity of rBmALT-2 was initially confirmed by demonstrating that it suppressed the lipopolysaccharide (LPS) induced nitric oxide synthesis and down-regulated the expression of pro-inflammatory cytokines in vitro by peritoneal exudate cells of mice. Treatment with rBmALT2 reduced severity of colitis associated with significant reduction in weight loss, disease activity, colon damage, mucosal edema and histopathological score including myeloperoxidase activity in colon tissues. rBmALT2 was comparatively more effective in attenuation of colitis when used in the preventive mode than when used for curative purpose. The therapeutic effect of rBmALT2 was found to be associated with downregulation of IFN-γ, IL-6, IL-17 and upregulation of IL-10 cytokines. These results provide strong experimental evidence that BmALT2 could be a potential alternative therapeutic agent in colitis. PMID:26669016

  1. Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis

    PubMed Central

    Hainzl, Eva; Rauch, Isabella; Heider, Susanne; Berry, David; Lassnig, Caroline; Schwab, Clarissa; Rosebrock, Felix; Milinovich, Gabriel; Schlederer, Michaela; Wagner, Michael; Schleper, Christa; Loy, Alexander; Urich, Tim; Kenner, Lukas; Han, Xiaonan; Decker, Thomas; Strobl, Birgit

    2015-01-01

    In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease. Colitic Tyk2−/− mice have less p-STAT3 in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22–STAT3 target genes is reduced in IECs from healthy and colitic Tyk2−/− mice. Experiments with conditional Tyk2−/− mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of rIL-22–Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22–dependent colitis was confirmed in Citrobacter rodentium–induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3. PMID:26432894

  2. IL-9 regulates intestinal barrier function in experimental T cell-mediated colitis.

    PubMed

    Gerlach, Katharina; McKenzie, Andrew N; Neurath, Markus F; Weigmann, Benno

    2015-01-01

    As previous studies suggested that IL-9 may control intestinal barrier function, we tested the role of IL-9 in experimental T cell-mediated colitis induced by the hapten reagent 2,4,6-trinitrobenzenesulfonic acid (TNBS). The deficiency of IL-9 suppressed TNBS-induced colitis and led to lower numbers of PU.1 expressing T cells in the lamia propria, suggesting a regulatory role for Th9 cells in the experimental TNBS colitis model. Since IL-9 is known to functionally alter intestinal barrier function in colonic inflammation, we assessed the expression of tight junction molecules in intestinal epithelial cells of TNBS-inflamed mice. Therefore we made real-time PCR analyses for tight junction molecules in the inflamed colon from wild-type and IL-9 KO mice, immunofluorescent stainings and investigated the expression of junctional proteins directly in intestinal epithelial cells of TNBS-inflamed mice by Western blot studies. The results demonstrated that sealing proteins like occludin were up regulated in the colon of inflamed IL-9 KO mice. In contrast, the tight junction protein Claudin1 showed lower expression levels when IL-9 is absent. Surprisingly, the pore-forming molecule Claudin2 revealed equal expression in TNBS-treated wild-type and IL-9-deficient animals. These results illustrate the pleiotropic functions of IL-9 in changing intestinal permeability in experimental colitis. Thus, modulation of IL-9 function emerges as a new approach for regulating barrier function in intestinal inflammation.

  3. Oral Bifidobacterium longum expressing alpha-melanocyte-stimulating hormone to fight experimental colitis.

    PubMed

    Wei, Pijin; Yang, Yan; Liu, Zhaobing; Huang, Junli; Gong, Yahui; Sun, Hanxiao

    2016-07-01

    The oral delivery of peptides is a highly attractive treatment approach. However, the harsh environment of the gastrointestinal tract limits its application. Here, we utilize Bifidobacterium as a delivery system to orally deliver a potent anti-inflammatory but short duration peptide alpha-melanocyte-stimulating hormone (α-MSH) against experimental colitis. The aim of our study was to facilitate the efficient oral delivery of α-MSH. We designed a vector of pBDMSH and used it to construct a Bifidobacterium longum expressing α-MSH. We then determined the bioactivity of recombinant Bifidobacterium in lipopolysaccharide-induced inflammatory models of HT-29 cells. Finally, we used Bifidobacterium expressing α-MSH against dextran sulfate sodium (DSS)-induced ulcerative colitis mice. Results based on the myeloperoxidase activity, the levels of inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-10 and the histological injury of colon tissue reveal recombinant Bifidobacterium was efficient in attenuating DSS-induced ulcerative colitis, suggesting an alternative way to use Bifidobacterium as a delivery system to deliver α-MSH for DSS-induced ulcerative colitis therapy. PMID:26673899

  4. Gastrointestinal endoscopy biopsy derived proteomic patterns predict indeterminate colitis into ulcerative colitis and Crohn’s colitis

    PubMed Central

    Ballard, Billy Ray; M’Koma, Amosy Ephreim

    2015-01-01

    Patients with indeterminate colitis (IC) are significantly younger at diagnosis with onset of symptoms before the age of 18 years with significant morbidity in the interim. The successful care of IC is based on microscopic visual predict precision of eventual ulcerative colitis (UC) or Crohn’s colitis (CC) which is not offered in 15%-30% of inflammatory bowel disease (IBD) patients even after a combined state-of-the-art classification system of clinical, visual endoscopic, radiologic and histologic examination. These figures have not changed over the past 3 decades despite the introduction of newer diagnostic modalities. The patient outcomes after restorative proctocolectomy and ileal pouch-anal anastomosis may be painstaking if IC turns into CC. Our approach is aiming at developing a single sensitive and absolute accurate diagnostic test tool during the first clinic visit through endoscopic biopsy derived proteomic patterns. Matrix-assisted-laser desorption/ionization mass spectrometry (MS) and/or imaging MS technologies permit a histology-directed cellular test of endoscopy biopsy which identifies phenotype specific proteins, as biomarker that would assist clinicians more accurately delineate IC as being either a UC or CC or a non-IBD condition. These novel studies are underway on larger cohorts and are highly innovative with significances in differentiating a UC from CC in patients with IC and could lend mechanistic insights into IBD pathogenesis. PMID:26140094

  5. Effect of different doses of Manuka honey in experimentally induced inflammatory bowel disease in rats.

    PubMed

    Prakash, A; Medhi, B; Avti, P K; Saikia, U N; Pandhi, P; Khanduja, K L

    2008-11-01

    To evaluate the effect of different doses of Manuka honey in experimentally induced inflammatory bowel disease in rats. Adult Wistar rats of either sex were used (n = 30). Colitis was induced by a single intracolonic administration of TNBS dissolved in 35% ethanol. The rats (n = 30) were divided into five groups (n = 6) and were treated with vehicle (ethanol), TNBS, Manuka honey (5 g/kg, p.o.), Manuka honey (10 g/kg, p.o.) or sulfasalazine (360 mg/kg, p.o.) body weight for 14 days. After completion of treatment, the animals were killed and the following parameters were assessed: morphological score, histological score and different antioxidant parameters.Manuka honey at different doses provided protection against TNBS-induced colonic damage. There was significant protection with Manuka honey 5 g/kg as well as with 10 g/kg body weight compared with the control (p < 0.001). All the treated groups showed reduced colonic inflammation and all the biochemical parameters were significantly reduced compared with the control in the Manuka honey treated groups (p < 0.001). Manuka honey at different doses restored lipid peroxidation as well as improved antioxidant parameters. Morphological and histological scores were significantly reduced in the low dose Manuka honey treated group (p < 0.001). In the inflammatory model of colitis, oral administration of Manuka honey 5 g/kg and Manuka honey 10 g/kg body weight significantly reduced the colonic inflammation. The present study indicates that Manuka honey is efficacious in the TNBS-induced rat colitis model, but these results require further confirmation in human studies.

  6. Lymphocytic colitis: clinical presentation and long term course

    PubMed Central

    Mullhaupt, B; Guller, U; Anabitarte, M; Guller, R; Fried, M

    1998-01-01

    Background—Lymphocytic colitis is characterised by chronic watery diarrhoea with normal endoscopic or radiological findings and microscopic evidence of pronounced infiltration of the colonic mucosa with lymphocytes.
Aim—To investigate the long term clinical and histological evolution of the disease in a large group of patients with well characterised lymphocytic colitis. 
Methods—Between 1986 and 1995 the histological diagnosis of lymphocytic colitis was obtained in 35 patients; 27 of these agreed to a follow up examination. All clinical, endoscopic, and histopathological records were reviewed at that time and the patients had a second endoscopic examination with follow up biopsies. 
Results—The patients initially presented with the typical findings of lymphocytic colitis. After a mean (SD) follow up of 37.8 (27.5) months, diarrhoea subsided in 25 (93%) and histological normalisation was observed in 22 (82%) of the 27 patients. Progression from lymphocytic colitis to collagenous colitis was not observed. 
Conclusions—Lymphocytic colitis is characterised by a benign course with resolution of diarrhoea and normalisation of histology in over 80% of patients within 38 months. Considering the benign course of the disease, the potential benefit of any drug treatment should be carefully weighed against its potential side effects. 

 Keywords: lymphocytic colitis; colitis; diarrhoea PMID:9824342

  7. Fulminant ulcerative colitis complicated by treatment-refractory bacteremia

    PubMed Central

    Krease, Michael; Stroup, Jeff; Som, Mousumi

    2016-01-01

    Severe ulcerative colitis is defined by more than six bloody stools daily and evidence of toxicity, demonstrated by fever, tachycardia, anemia, or an elevated erythrocyte sedimentation rate. Fulminant disease represents a subset of severe disease with signs and symptoms suggestive of increased toxicity. Treatment of severe colitis includes intravenous corticosteroid administration, with consideration of intravenous infliximab 5 mg/kg. Failure to show improvement after 3 to 5 days is an indication for colectomy or treatment with intravenous cyclosporine. We report a 23-year-old Hispanic woman with decompensated cirrhosis presenting with new-onset fulminant ulcerative colitis and resulting polymicrobial bacteremia, requiring colectomy for infection source control and colitis treatment.

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

    PubMed

    Somani, Sahil; Zambad, Shitalkumar; Modi, Ketan

    2016-06-25

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

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

    PubMed Central

    Lombardi, Valter R. M.; Etcheverría, Ignacio; Carrera, Iván; Cacabelos, Ramón; Chacón, Antonio R.

    2012-01-01

    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. PMID:22619498

  10. [The contagious behavior model on the basis of rat drinking behavior].

    PubMed

    Ivanov, D G; Semenov, A N; Krupina, N A

    2014-01-01

    In work, the attempt of contagious behavior modeling on the basis of rat drinking behavior was made. Rats' behavior was observed in home cage with two bottles. The rat without drinking motivation (viewer) was placed in the cage for adaptation. The rat-demonstrator was placed into the same cage 3 minutes later. If the viewer was tested with drink-motivated demonstrator, it had less latency of approach to bottles, higher frequency of approaches and increased drinking behavior time than the rat tested with unmotivated demonstrator or the rat tested without demonstrator. The intragastric infusion of coffee increased frequency of approaches to demonstrated bottle. Phenazepam intragastric injection decreased frequency of approaches and drinking behavior time at demonstrated bottle. The results suggest that drugs may affect rat contagious behavior based on drinking behavior.

  11. A BBDR-HPT Axis Model for the Pregnant Rat and Fetus: Evaluation of Iodide Deficiency

    EPA Science Inventory

    A biologically based dose response (BBDR) model for the hypothalamic-pituitarythyroid (HPT) axis for the pregnant rat and fetus is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the pregnant rat and fet...

  12. Allergic colitis in monozygotic preterm twins.

    PubMed

    Baldassarre, Maria Elisabetta; Cappiello, Annarita; Laforgia, Nicola; Vanderhoof, Jon

    2013-02-01

    Allergic colitis (AC) typically develops in the first weeks or months of life and is characterized by the presence of red blood in the stools of healthy breastfed or formula fed infants. In this paper, we describe a case of rectal bleeding in monozygotic preterm twins that was resolved with the introduction of a cow's milk protein-free diet (CMPFD). The occurrence of this disorder in monozygotic twins raises the question as to whether the underlying abnormality in the immune regulation, which leads to poor acquisition of tolerance to cow's milk proteins, might be inherited or environmentally acquired. The case also highlights the use of the probiotic Lactobacillus GG (LGG) in the treatment of allergic colitis. PMID:23098248

  13. Isolated naratriptan-associated ischemic colitis

    PubMed Central

    Nissan, George; Chaudhry, Priyanka; Rangasamy, Priya; Mudrovich, Steven

    2016-01-01

    We report a 41-year-old woman who developed histology- and colonoscopy-proven ischemic colitis with the use of naratriptan not exceeding the maximum 2 doses a day and 3 days per week and without a known medical or cardiovascular history. By exclusion of other causes of colonic ischemia, naratriptan was considered the sole causal agent. Discontinuation of naratriptan resulted in a complete clinical recovery. To date, our patient is the youngest known patient to develop ischemic colitis on isolated naratriptan in the setting of no known medical risk factors or predisposing medical condition. Even though triptans are commonly used for the abortive treatment of migraine headaches, such a reported side effect is rare; however, careful assessment and individual patient-based treatment is advised.

  14. Isolated naratriptan-associated ischemic colitis

    PubMed Central

    Nissan, George; Chaudhry, Priyanka; Rangasamy, Priya; Mudrovich, Steven

    2016-01-01

    We report a 41-year-old woman who developed histology- and colonoscopy-proven ischemic colitis with the use of naratriptan not exceeding the maximum 2 doses a day and 3 days per week and without a known medical or cardiovascular history. By exclusion of other causes of colonic ischemia, naratriptan was considered the sole causal agent. Discontinuation of naratriptan resulted in a complete clinical recovery. To date, our patient is the youngest known patient to develop ischemic colitis on isolated naratriptan in the setting of no known medical risk factors or predisposing medical condition. Even though triptans are commonly used for the abortive treatment of migraine headaches, such a reported side effect is rare; however, careful assessment and individual patient-based treatment is advised. PMID:27695179

  15. Ulcerative Colitis: Update on Medical Management.

    PubMed

    Iskandar, Heba N; Dhere, Tanvi; Farraye, Francis A

    2015-11-01

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease whose pathogenesis is multifactorial and includes influences from genes, the environment, and the gut microbiome. Recent advances in diagnosis and treatment have led to significant improvement in managing the disease. Disease monitoring with the use of therapeutic drug monitoring, stool markers, and assessment of mucosal healing have garnered much attention. The recent approval of vedolizumab for treatment of moderate to severe UC has been a welcome addition. Newer biologics, including those targeting the Janus tyrosine kinase (JAK) pathway, are on the horizon to add to the current armamentarium of anti-TNF alpha and anti-integrin therapies. The recent publication of the SCENIC consensus statement on surveillance and management of dysplasia in UC patients supports the use of chromoendoscopy over random biopsies in detecting dysplasia. This review highlights these recent advances along with others that have been made with ulcerative colitis.

  16. Respiratory tract lung geometry and dosimetry model for male Sprague-Dawley rats.

    SciTech Connect

    Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.; Price, Owen; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Cox, Timothy C.; Kabilan, Senthil; Bentley, Timothy

    2014-08-26

    While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract model for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague- Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.

  17. Respiratory Tract Lung Geometry and Dosimetry Model for Male Sprague-Dawley Rats

    SciTech Connect

    Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.; Price, Owen; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Cox, Timothy C.; Kabilan, Senthil; Bentley, Timothy

    2015-07-24

    While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract model for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague-Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.

  18. Ischemic Colitis in an Endurance Runner

    PubMed Central

    Grames, Chase; Berry-Cabán, Cristóbal S.

    2012-01-01

    A 20-year-old female running the Marine Corps Marathon developed diarrhea at mile 12. After finishing the race she noted that she was covered in bloody stool. A local emergency department suspected ischemic colitis. After discharge, her primary care physician instructed her to discontinue the use of all nonsteroidal anti-inflammatory drugs. Her symptoms resolved and she returned to running without any complications. This paper describes the pathophysiology, diagnostic approach, and management options. PMID:23091744

  19. Polyphenol-rich sorghum brans alter colon microbiota and impact species diversity and species richness after multiple bouts of dextran sodium sulfate-induced colitis.

    PubMed

    Ritchie, Lauren E; Sturino, Joseph M; Carroll, Raymond J; Rooney, Lloyd W; Azcarate-Peril, M Andrea; Turner, Nancy D

    2015-03-01

    The microbiota affects host health, and dysbiosis is involved in colitis. Sorghum bran influences butyrate concentrations during dextran sodium sulfate (DSS) colitis, suggesting microbiota changes. We aimed to characterize the microbiota during colitis, and ascertain if polyphenol-rich sorghum bran diets mitigate these effects. Rats (n = 80) were fed diets containing 6% fiber from cellulose, or Black (3-deoxyanthocyanins), Sumac (condensed tannins), or Hi Tannin black (both) sorghum bran. Inflammation was induced three times using 3% DSS for 48 h (40 rats, 2 week separation), and the microbiota characterized by pyrosequencing. The Firmicutes/Bacteroidetes ratio was higher in Cellulose DSS rats. Colonic injury negatively correlated with Firmicutes, Actinobacteria, Lactobacillales and Lactobacillus, and positively correlated with Unknown/Unclassified. Post DSS#2, richness was significantly lower in Sumac and Hi Tannin black. Post DSS#3 Bacteroidales, Bacteroides, Clostridiales, Lactobacillales and Lactobacillus were reduced, with no Clostridium identified. Diet significantly affected Bacteroidales, Bacteroides, Clostridiales and Lactobacillus post DSS#2 and #3. Post DSS#3 diet significantly affected all genus, including Bacteroides and Lactobacillus, and diversity and richness increased. Sumac and Hi Tannin black DSS had significantly higher richness compared to controls. Thus, these sorghum brans may protect against alterations observed during colitis including reduced microbial diversity and richness, and dysbiosis of Firmicutes/Bacteroidetes.

  20. Polyphenol-rich sorghum brans alter colon microbiota and impact species diversity and species richness after multiple bouts of dextran sodium sulfate-induced colitis.

    PubMed

    Ritchie, Lauren E; Sturino, Joseph M; Carroll, Raymond J; Rooney, Lloyd W; Azcarate-Peril, M Andrea; Turner, Nancy D

    2015-03-01

    The microbiota affects host health, and dysbiosis is involved in colitis. Sorghum bran influences butyrate concentrations during dextran sodium sulfate (DSS) colitis, suggesting microbiota changes. We aimed to characterize the microbiota during colitis, and ascertain if polyphenol-rich sorghum bran diets mitigate these effects. Rats (n = 80) were fed diets containing 6% fiber from cellulose, or Black (3-deoxyanthocyanins), Sumac (condensed tannins), or Hi Tannin black (both) sorghum bran. Inflammation was induced three times using 3% DSS for 48 h (40 rats, 2 week separation), and the microbiota characterized by pyrosequencing. The Firmicutes/Bacteroidetes ratio was higher in Cellulose DSS rats. Colonic injury negatively correlated with Firmicutes, Actinobacteria, Lactobacillales and Lactobacillus, and positively correlated with Unknown/Unclassified. Post DSS#2, richness was significantly lower in Sumac and Hi Tannin black. Post DSS#3 Bacteroidales, Bacteroides, Clostridiales, Lactobacillales and Lactobacillus were reduced, with no Clostridium identified. Diet significantly affected Bacteroidales, Bacteroides, Clostridiales and Lactobacillus post DSS#2 and #3. Post DSS#3 diet significantly affected all genus, including Bacteroides and Lactobacillus, and diversity and richness increased. Sumac and Hi Tannin black DSS had significantly higher richness compared to controls. Thus, these sorghum brans may protect against alterations observed during colitis including reduced microbial diversity and richness, and dysbiosis of Firmicutes/Bacteroidetes. PMID:25764457

  1. Brattleboro Rats as the Model of Blood Hyperviscosity Syndrome for Testing Substances with Hemorheological Activity.

    PubMed

    Plotnikov, M B; Vasil'ev, A S; Aliev, O I; Zibareva, L N

    2015-09-01

    Hyperviscosity syndrome was described in Brattleboro rats. The aim of this study was to investigate the possibility of Brattleboro rats using, as a test system for the study of agents with hemorheological activity. Under conditions of this model of high blood viscosity syndrome in Brattleboro rats, Lychnis chalcedonica L. extract (150 mg/kg) administered intragastrically for 10 days exhibited hemorheological activity by modulating macro- (plasma viscosity, fibrinogen concentration) and microrheological (erythrocyte aggregation and deformability parameters. Hence, Brattleboro rats are an adequate model of hyperviscosity syndrome that can be used for search and testing of substances with hemorheological activity. PMID:26463056

  2. Ulcerative Colitis: A Challenge to Surgeons

    PubMed Central

    Parray, Fazl Q; Wani, Mohd L; Malik, Ajaz A; Wani, Shadab N; Bijli, Akram H; Irshad, Ifat; Nayeem-Ul-Hassan

    2012-01-01

    Ulcerative colitis is a chronic disease that specifically affects the mucosa of the rectum and colon. Although the etiology of this recurring inflammatory disorder remains essentially unknown, there have been significant advances in identifying the likely genetic and environmental factors that contribute to its pathogenesis. The clinical course of the disease typically manifests with remissions and exacerbations characterized by rectal bleeding and diarrhea. Since ulcerative colitis most commonly affects patients in their youth or early middle age, the disease can have serious long-term local and systemic consequences. There is no specific medical therapy that is curative. Although medical therapy can ameliorate the inflammatory process and control most symptomatic flares, it provides no definitive treatment for the disease. Proctocolectomy or total removal of the colon and rectum provides the only complete cure; however, innovative surgical alternatives have eliminated the need for a permanent ileostomy. The aim of this review is to provide a detailed account of the surgical management of ulcerative colitis. PMID:23189226

  3. The Synergic Anti-inflammatory Impact of Gleditsia sinensis Lam. and Lactobacillus brevis KY21 on Intestinal Epithelial Cells in a DSS-induced Colitis Model.

    PubMed

    Kim, Younghoon; Koh, Ji Hoon; Ahn, Young Jun; Oh, Sejong; Kim, Sea Hun

    2015-01-01

    We investigated the synergic anti-inflammatory activity of Gleditsia sinensis Lam. (GS) extract and Lactobacillus brevis KY21 both in vitro and in vivo. Western blot analysis and immunostaining showed that AKT phosphorylation that increased by the exposure of LPS were significantly decreased by the presence of either GS extract or L. brevis KY21. In addition, p65 intracellular transport was critically inhibited by GS extract and L. brevis KY21. We further studied these effects using an in vivo dextran sulfate sodium (DSS)-induced mouse model. Body weight, food intake, and clinical scores were dramatically decreased after treatment with DSS, whereas these effects were palliated by the addition of GS extract and L. brevis KY21. Importantly, transcription of genes encoding pro-inflammatory cytokines including IL-1β, TNF-α, and IFN-γ in mesenteric lymph nodes (MLN) and the spleen were increased by DSS treatment, whereas they were inhibited by the presence of GS extract and L. brevis KY21.

  4. Zinc supplementation decreases hepatic copper accumulation in LEC rat: a model of Wilson's disease.

    PubMed

    Gonzalez, Blanca P Esparza; Niño Fong, Rodolfo; Gibson, Candace J; Fuentealba, I Carmen; Cherian, M George

    2005-01-01

    The effect of dietary zinc (Zn) supplementation on copper (Cu)-induced liver damage was investigated in Long-Evans Cinnamon rats (LEC), a model for Wilson's disease (WD). Four-week-old LEC (N=64) and control Long-Evans (LE) (N=32) female rats were divided into two groups; one group was fed with a Zn-supplemented diet (group I) and the other was given a normal rodent diet (group II). LEC rats were killed at 6, 8, 10, 12, 18, and 20 wk of age; the LE control rats were killed at 6, 12, 18, and 20 wk of age. Cu concentration in the liver was reduced in LEC rats fed the Zn-supplemented diet compared with LEC rats on the normal diet between 6 and 18 wk of age. Metallothionein (MT) concentration in the livers of LEC rats in group I increased between 12 and 20 wk of age, whereas hepatic MT concentration in LEC rats from group II decreased after 12 wk. Hepatocyte apoptosis, as determined by TUNEL, was reduced in Zn-supplemented LEC rats at all ages. Cholangiocellular carcinoma was observed only in LEC rats in group II at wk 20. These results suggest that Zn supplementation can reduce hepatic Cu concentration and delay the onset of clinical and pathological changes of Cu toxicity in LEC rats. Although the actual mechanism of protection is unknown, it could be explained by sequestration of dietary Cu by intestinal MT, induced by high dietary Zn content.

  5. A new model of progressive pulmonary fibrosis in rats

    SciTech Connect

    Last, J.A.; Gelzleichter, T.R.; Pinkerton, K.E.; Walker, R.M.; Witschi, H. )

    1993-08-01

    Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.

  6. Rheumatoid arthritis: identifying and characterising polymorphisms using rat models

    PubMed Central

    2016-01-01

    ABSTRACT Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans. PMID:27736747

  7. Altered explorative strategies and reactive coping style in the FSL rat model of depression

    PubMed Central

    Magara, Salvatore; Holst, Sarah; Lundberg, Stina; Roman, Erika; Lindskog, Maria

    2015-01-01

    Modeling depression in animals is based on the observation of behaviors interpreted as analog to human symptoms. Typical tests used in experimental depression research are designed to evoke an either-or outcome. It is known that explorative and coping strategies are relevant for depression, however these aspects are generally not considered in animal behavioral testing. Here we investigate the Flinders Sensitive Line (FSL), a rat model of depression, compared to the Sprague-Dawley (SD) rat in three independent tests where the animals are allowed to express a more extensive behavioral repertoire. The multivariate concentric square field™ (MCSF) and the novel cage tests evoke exploratory behaviors in a novel environment and the home cage change test evokes social behaviors in the re-establishment of a social hierarchy. In the MCSF test, FSL rats exhibited less exploratory drive and more risk-assessment behavior compared to SD rats. When re-exposed to the arena, FSL, but not SD rats, increased their exploratory behavior compared to the first trial and displayed risk-assessment behavior to the same extent as SD rats. Thus, the behavior of FSL rats was more similar to that of SDs when the rats were familiar with the arena. In the novel cage test FSL rats exhibited a reactive coping style, consistent with the reduced exploration observed in the MCSF. Reactive coping is associated with less aggressive behavior. Accordingly, FSL rats displayed less aggressive behavior in the home cage change test. Taken together, our data show that FSL rats express altered exploratory behavior and reactive coping style. Reduced interest is a core symptom of depression, and individuals with a reactive coping style are more vulnerable to the disease. Our results support the use of FSL rats as an animal model of depression and increase our understanding of the FSL rat beyond the behavioral dimensions targeted by the traditional depression-related tests. PMID:25954168

  8. Modeling the Nonlinear Motion of the Rat Central Airways.

    PubMed

    Ibrahim, G; Rona, A; Hainsworth, S V

    2016-01-01

    Advances in volumetric medical imaging techniques allowed the subject-specific modeling of the bronchial flow through the first few generations of the central airways using computational fluid dynamics (CFD). However, a reliable CFD prediction of the bronchial flow requires modeling of the inhomogeneous deformation of the central airways during breathing. This paper addresses this issue by introducing two models of the central airways motion. The first model utilizes a node-to-node mapping between the discretized geometries of the central airways generated from a number of successive computed tomography (CT) images acquired dynamically (without breath hold) over the breathing cycle of two Sprague-Dawley rats. The second model uses a node-to-node mapping between only two discretized airway geometries generated from the CT images acquired at end-exhale and at end-inhale along with the ventilator measurement of the lung volume change. The advantage of this second model is that it uses just one pair of CT images, which more readily complies with the radiation dosage restrictions for humans. Three-dimensional computer aided design geometries of the central airways generated from the dynamic-CT images were used as benchmarks to validate the output from the two models at sampled time-points over the breathing cycle. The central airway geometries deformed by the first model showed good agreement to the benchmark geometries within a tolerance of 4%. The central airway geometry deformed by the second model better approximated the benchmark geometries than previous approaches that used a linear or harmonic motion model.

  9. Modeling the Nonlinear Motion of the Rat Central Airways.

    PubMed

    Ibrahim, G; Rona, A; Hainsworth, S V

    2016-01-01

    Advances in volumetric medical imaging techniques allowed the subject-specific modeling of the bronchial flow through the first few generations of the central airways using computational fluid dynamics (CFD). However, a reliable CFD prediction of the bronchial flow requires modeling of the inhomogeneous deformation of the central airways during breathing. This paper addresses this issue by introducing two models of the central airways motion. The first model utilizes a node-to-node mapping between the discretized geometries of the central airways generated from a number of successive computed tomography (CT) images acquired dynamically (without breath hold) over the breathing cycle of two Sprague-Dawley rats. The second model uses a node-to-node mapping between only two discretized airway geometries generated from the CT images acquired at end-exhale and at end-inhale along with the ventilator measurement of the lung volume change. The advantage of this second model is that it uses just one pair of CT images, which more readily complies with the radiation dosage restrictions for humans. Three-dimensional computer aided design geometries of the central airways generated from the dynamic-CT images were used as benchmarks to validate the output from the two models at sampled time-points over the breathing cycle. The central airway geometries deformed by the first model showed good agreement to the benchmark geometries within a tolerance of 4%. The central airway geometry deformed by the second model better approximated the benchmark geometries than previous approaches that used a linear or harmonic motion model. PMID:26592166

  10. Single Nucleotide Polymorphisms that Increase Expression of the GTPase RAC1 are Associated with Ulcerative Colitis

    PubMed Central

    Muise, Aleixo M; Walters, Thomas; Xu, Wei; Shen-Tu, Grace; Guo, Cong-Hui; Fattouh, Ramzi; Lam, Grace Y; Wolters, Victorien M; Bennitz, Joshua; Van Limbergen, Johan; Renbaum, Paul; Kasirer, Yair; Ngan, Bo-Yee; Turner, Dan; Denson, Lee A; Sherman, Philip M; Duerr, Richard H; Cho, Judy; Lees, Charlie W; Satsangi, Jack; Wilson, David C; Paterson, Andrew D; Griffiths, Anne M; Glogauer, Michael; Silverberg, Mark S; Brumell, John H

    2011-01-01

    Background & Aims RAC1 is a GTPase that has an evolutionarily conserved role in coordinating immune defenses, from plants to mammals. Chronic inflammatory bowel diseases (IBD) are associated with dysregulation of immune defenses. We studied the role of RAC1 in IBD using human genetic and functional studies and animal models of colitis. Methods We used a candidate gene approach to HapMap-Tag single nucleotide polymorphisms (SNPs) in a discovery cohort; findings were confirmed in 2 additional cohorts. RAC1 mRNA expression was examined from peripheral blood cells of patients. Colitis was induced in mice with conditional disruption of Rac1 in phagocytes by administration of dextran sulphate sodium (DSS). Results We observed a genetic association between RAC1 with ulcerative colitis (UC) in a discovery cohort, 2 independent replication cohorts, and in combined analysis for the SNPs rs10951982 (Pcombined UC = 3.3 × 10–8, odds ratio [OR]=1.43 [1.26–1.63]) and rs4720672 (Pcombined UC=4.7 × 10–6, OR=1.36 [1.19–1.58]). Patients with IBD who had the rs10951982 risk allele had increased expression of RAC1, compared to those without this allele. Conditional disruption of Rac1 in macrophage and neutrophils of mice protected them against DSS-induced colitis. Conclusion Studies of human tissue samples and knockout mice demonstrated a role for the GTPase RAC1 in the development of UC; increased expression of RAC1 was associated with susceptibility to colitis. PMID:21684284

  11. Melatonin modulates adiponectin expression on murine colitis with sleep deprivation

    PubMed Central

    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

    2016-01-01

    AIM To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. METHODS 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 intraperitoneal