An entirely automated method to score DSS-induced colitis in mice by digital image analysis of pathology slides

PubMed Central

Kozlowski, Cleopatra; Jeet, Surinder; Beyer, Joseph; Guerrero, Steve; Lesch, Justin; Wang, Xiaoting; DeVoss, Jason; Diehl, Lauri

2013-01-01

SUMMARY The DSS (dextran sulfate sodium) model of colitis is a mouse model of inflammatory bowel disease. Microscopic symptoms include loss of crypt cells from the gut lining and infiltration of inflammatory cells into the colon. An experienced pathologist requires several hours per study to score histological changes in selected regions of the mouse gut. In order to increase the efficiency of scoring, Definiens Developer software was used to devise an entirely automated method to quantify histological changes in the whole H&E slide. When the algorithm was applied to slides from historical drug-discovery studies, automated scores classified 88% of drug candidates in the same way as pathologists’ scores. In addition, another automated image analysis method was developed to quantify colon-infiltrating macrophages, neutrophils, B cells and T cells in immunohistochemical stains of serial sections of the H&E slides. The timing of neutrophil and macrophage infiltration had the highest correlation to pathological changes, whereas T and B cell infiltration occurred later. Thus, automated image analysis enables quantitative comparisons between tissue morphology changes and cell-infiltration dynamics. PMID:23580198

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Ergosterol peroxide from Chaga mushroom (Inonotus obliquus) exhibits anti-cancer activity by down-regulation of the β-catenin pathway in colorectal cancer.

PubMed

Kang, Ju-Hee; Jang, Jeong-Eun; Mishra, Siddhartha Kumar; Lee, Hee-Ju; Nho, Chu Won; Shin, Dongyun; Jin, Mirim; Kim, Mi Kyung; Choi, Changsun; Oh, Seung Hyun

2015-09-15

In this study, we examined the effect of different fractions and components of Chaga mushroom (Inonotus Obliquus) on viability and apoptosis of colon cancer cells. Among them, one component showed the most effective growth inhibition and was identified as ergosterol peroxide by NMR analysis. We investigated the anti-proliferative and apoptosis mechanisms of ergosterol peroxide associated with its anti-cancer activities in human colorectal cancer (CRC) cell lines and tested its anti-tumor effect on colitis-induced CRC developed by Azoxymethane (AOM)/Dextran sulfate sodium (DSS) in a mouse model. We used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, flow cytometry assays, Western blot analysis, colony formation assays, reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and AOM/DSS mouse models to study the molecular mechanism of metastatic activities in CRC cells. Ergosterol peroxide inhibited cell proliferation and also suppressed clonogenic colony formation in HCT116, HT-29, SW620 and DLD-1 CRC cell lines. The growth inhibition observed in these CRC cell lines was the result of apoptosis, which was confirmed by FACS analysis and Western blotting. Ergosterol peroxide inhibited the nuclear levels of β-catenin, which ultimately resulted in reduced transcription of c-Myc, cyclin D1, and CDK-8. Ergosterol peroxide administration showed a tendency to suppress tumor growth in the colon of AOM/DSS-treated mice, and quantification of the IHC staining showed a dramatic decrease in the Ki67-positive staining and an increase in the TUNEL staining of colonic epithelial cells in AOM/DSS-treated mice by ergosterol peroxide for both prevention and therapy. Our data suggest that ergosterol peroxide suppresses the proliferation of CRC cell lines and effectively inhibits colitis-associated colon cancer in AOM/DSS-treated mice. Ergosterol peroxide down-regulated β-catenin signaling, which exerted anti-proliferative and pro-apoptotic activities in CRC cells. These properties of ergosterol peroxide advocate its use as a supplement in colon cancer chemoprevention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sasa quelpaertensis leaf extract regulates microbial dysbiosis by modulating the composition and diversity of the microbiota in dextran sulfate sodium-induced colitis mice.

PubMed

Yeom, Yiseul; Kim, Bong-Soo; Kim, Se-Jae; Kim, Yuri

2016-11-25

Inflammatory bowel diseases (IBD) are related to a dysfunction of the mucosal immune system and they result from complex interactions between genetics and environmental factors, including lifestyle, diet, and the gut microbiome. Therefore, the effect of Sasa quelpaertensis leaf extract (SQE) on gut microbiota in a dextran sulfate sodium (DSS)-induced colitis mouse model was investigated with pyrosequencing of fecal samples. Three groups of animals were examined: i) a control group, ii) a group that was received 2.5% DSS in their drinking water for 7 days, followed by 7 days of untreated water, and then another 7 days of 2.5% DSS in their drinking water, and iii) a group that was presupplemented with SQE (300 mg/kg body weight) by gavage for two weeks prior to the same DSS treatment schedule described in ii. SQE supplementation alleviated disease activity scores and shortened colon length compared to the other two groups. In the DSS group, the proportion of Bacteroidetes increased, whereas that the proportion of Firmicutes was decreased compared to the control group. SQE supplementation recovered the proportions of Firmicutes and Bacteroidetes back to control levels. Moreover, the diversity of microbiota in the SQE supplementation group higher than that of the DSS group. SQE was found to protect mice from microbial dysbiosis associated with colitis by modulating the microbial composition and diversity of the microbiota present. These results provide valuable insight into microbiota-food component interactions in IBD.

Modulation of the microbiota-gut-brain axis by probiotics in a murine model of inflammatory bowel disease.

PubMed

Emge, Jacob R; Huynh, Kevin; Miller, Elaine N; Kaur, Manvir; Reardon, Colin; Barrett, Kim E; Gareau, Mélanie G

2016-06-01

Anxiety, depression, and altered memory are associated with intestinal diseases, including inflammatory bowel disease (IBD). Understanding the link between these behavioral changes and IBD is important clinically since concomitant mood disorders often increase a patient's risk of requiring surgery and developing secondary functional gastrointestinal diseases. Anxiety-like behavior (light/dark box test) and recognition memory (novel object recognition task) were determined at the peak and during resolution of inflammation in the dextran sodium sulfate (DSS) mouse model of acute colitis. DSS (5 days) was administered via drinking water followed by 3 or 9 days of normal drinking water to assess behavior during active or resolving inflammation, respectively. Disease (weight, colon length, and histology) was assessed and the composition of the gut microbiota was characterized by using qPCR on fecal pellet DNA. In a subset of mice, pretreatment with probiotics was started 1 wk prior to commencing DSS. During active inflammation (8 days), mice demonstrated impaired recognition memory and exhibited anxiety-like behavior vs. These behavioral defects were normalized by 14 days post-DSS. Shifts in the composition of the gut microbiota were evident during active inflammation, notably as decreases in lactobacilli and segmented filamentous bacteria, which were also reversed once the disease had resolved. Administration of probiotics could prevent the behavioral defects seen in acute DSS. Taken together, our findings indicate that changes in mood and behavior are present during acute inflammation in murine IBD and associated with dysbiosis and that these outcomes can be prevented by the administration of probiotics. Copyright © 2016 the American Physiological Society.

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

PubMed Central

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

2015-01-01

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. PMID:26013555

An orally administered butyrate-releasing derivative reduces neutrophil recruitment and inflammation in dextran sulphate sodium-induced murine colitis.

PubMed

Simeoli, Raffaele; Mattace Raso, Giuseppina; Pirozzi, Claudio; Lama, Adriano; Santoro, Anna; Russo, Roberto; Montero-Melendez, Trinidad; Berni Canani, Roberto; Calignano, Antonio; Perretti, Mauro; Meli, Rosaria

2017-06-01

Butyrate has shown benefits in inflammatory bowel diseases. However, it is not often administered orally because of its rancid smell and unpleasant taste. The efficacy of a more palatable butyrate-releasing derivative, N-(1-carbamoyl-2-phenylethyl) butyramide (FBA), was evaluated in a mouse model of colitis induced by dextran sodium sulphate (DSS). Male 10 week-old BALB/c mice received DSS (2.5%) in drinking water (for 5 days) followed by DSS-free water for 7 days (DSS group). Oral FBA administration (42.5 mg·kg -1 ) was started 7 days before DSS as preventive (P-FBA), or 2 days after DSS as therapeutic (T-FBA); both treatments lasted 19 days. One DSS-untreated group received only tap water (CON). FBA treatments reduced colitis symptoms and colon damage. P-FBA and T-FBA significantly decreased polymorphonuclear cell infiltration score compared with the DSS group. FBA reversed the imbalance between pro- and anti-inflammatory cytokines (reducing inducible NOS protein expression, CCL2 and IL-6 transcripts in colon and increasing TGFβ and IL-10). Morever, P-FBA and T-FBA limited neutrophil recruitment (by expression and localization of the neutrophil granule protease Ly-6G), restored deficiency of the butyrate transporter and improved intestinal epithelial integrity, preventing tight-junction impairment (zonulin-1 and occludin). FBA, similar to its parental compound sodium butyrate, inhibited histone deacetylase-9 and restored H3 histone acetylation, exerting an anti-inflammatory effect through NF-κB inhibition and the up-regulation of PPARγ. FBA reduces inflammatory intestinal damage in mice indicating its potential as a postbiotic derivative without the problems associated with the oral administration of sodium butyrate. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

Tea Polysaccharide Prevents Colitis-Associated Carcinogenesis in Mice by Inhibiting the Proliferation and Invasion of Tumor Cells

PubMed Central

Liu, Li-Qiao; Li, Hai-Shan; Shen, Ming-Yue; Hu, Jie-Lun; Xie, Ming-Yong

2018-01-01

The imbalance between cell proliferation and apoptosis can lead to tumor progression, causing oncogenic transformation, abnormal cell proliferation and cell apoptosis suppression. Tea polysaccharide (TPS) is the major bioactive component in green tea, it has showed antioxidant, antitumor and anti-inflammatory bioactivities. In this study, the chemoprophylaxis effects of TPS on colitis-associated colon carcinogenesis, especially the cell apoptosis activation and inhibition effects on cell proliferation and invasion were analyzed. The azoxymethane/dextran sulfate sodium (AOM/DSS) was used to induce the colorectal carcinogenesis in mice. Results showed that the tumor incidence was reduced in TPS-treated AOM/DSS mice compared to AOM/DSS mice. TUNEL staining and Ki-67 immunohistochemistry staining showed that the TPS treatment increased significantly the cell apoptosis and decreased cell proliferation among AOM/DSS mice. Furthermore, TPS reduced the expression levels of the cell cycle protein cyclin D1, matrix metalloproteinase (MMP)-2, and MMP-9. In addition, in vitro studies showed that TPS, suppressed the proliferation and invasion of the mouse colon cancer cells. Overall, our findings demonstrated that TPS could be a potential agent in the treatment and/or prevention of colon tumor, which promoted the apoptosis and suppressed the proliferation and invasion of the mouse colon cancer cells via arresting cell cycle progression. PMID:29419740

Short-chain fatty acids administration is protective in colitis-associated colorectal cancer development.

PubMed

Tian, Yun; Xu, Qing; Sun, Liqun; Ye, Ying; Ji, Guozhong

2018-03-17

Reduced short-chain fatty acids (SCFAs) have been reported in patients with ulcerative colitis, and increased intake of dietary fiber has shown to be clinically beneficial for colitis. Whether SCFAs suppress tumorigenesis in colitis-associated colorectal cancer remains unknown. The chemopreventive effect of SCFAs in colitis-associated colorectal cancer was evaluated in this study. Model of colitis-associated colorectal cancer in male BALB/c mice was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). SCFAs mix (67.5 mM acetate, 40 mM butyrate, 25.9 mM propionate) was administered in drink water during the study period. Macroscopic and histological studies were performed to examine the colorectal inflammation and tumorigenesis in AOM/DSS-induced mice treated with or without SCFA mix. The effects of SCFAs mix on colonic epithelial cellular proliferation were also assessed using Ki67 immunohistochemistry and TUNEL staining. The administration of SCFAs mix significantly reduced the tumor incidence and size in mice with AOM/DSS-induced colitis associated colorectal cancer. SCFAs mix protected from AOM/DSS-induced colorectal cancer by improving colon inflammation and disease activity index score as well as suppressing the expression of proinflammatory cytokines including IL-6, TNF-α and IL-17. A decrease in cell proliferation markers and an increase in TUNEL-positive tumor epithelial cells were also demonstrated in AOM/DSS mice treated with SCFAs mix. SCFAs mix administration prevented development of tumor and attenuated the colonic inflammation in a mouse model of colitis-associated colorectal cancer. SCFAs mix may be a potential agent in the prevention and treatment of colitis-associated colorectal cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Calcium/Ask1/MKK7/JNK2/c-Src signalling cascade mediates disruption of intestinal epithelial tight junctions by dextran sulfate sodium.

PubMed

Samak, Geetha; Chaudhry, Kamaljit K; Gangwar, Ruchika; Narayanan, Damodaran; Jaggar, Jonathan H; Rao, RadhaKrishna

2015-02-01

Disruption of intestinal epithelial tight junctions is an important event in the pathogenesis of ulcerative colitis. Dextran sodium sulfate (DSS) induces colitis in mice with symptoms similar to ulcerative colitis. However, the mechanism of DSS-induced colitis is unknown. We investigated the mechanism of DSS-induced disruption of intestinal epithelial tight junctions and barrier dysfunction in Caco-2 cell monolayers in vitro and mouse colon in vivo. DSS treatment resulted in disruption of tight junctions, adherens junctions and actin cytoskeleton leading to barrier dysfunction in Caco-2 cell monolayers. DSS induced a rapid activation of c-Jun N-terminal kinase (JNK), and the inhibition or knockdown of JNK2 attenuated DSS-induced tight junction disruption and barrier dysfunction. In mice, DSS administration for 4 days caused redistribution of tight junction and adherens junction proteins from the epithelial junctions, which was blocked by JNK inhibitor. In Caco-2 cell monolayers, DSS increased intracellular Ca(2+) concentration, and depletion of intracellular Ca(2+) by 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester) (BAPTA/AM) or thapsigargin attenuated DSS-induced JNK activation, tight junction disruption and barrier dysfunction. Knockdown of apoptosis signal-regulated kinase 1 (Ask1) or MKK7 blocked DSS-induced tight junction disruption and barrier dysfunction. DSS activated c-Src by a Ca2+ and JNK-dependent mechanism. Inhibition of Src kinase activity or knockdown of c-Src blocked DSS-induced tight junction disruption and barrier dysfunction. DSS increased tyrosine phosphorylation of occludin, zonula occludens-1 (ZO-1), E-cadherin and β-catenin. SP600125 abrogated DSS-induced tyrosine phosphorylation of junctional proteins. Recombinant JNK2 induced threonine phosphorylation and auto-phosphorylation of c-Src. The present study demonstrates that Ca(2+)/Ask1/MKK7/JNK2/cSrc signalling cascade mediates DSS-induced tight junction disruption and barrier dysfunction.

Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis.

PubMed

Oh, Sa-Rang; Ok, Seon; Jung, Tae-Sung; Jeon, Sang-Ok; Park, Ji-Min; Jung, Ji-Wook; Ryu, Deok-Seon

2017-09-01

To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC). The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α, PGE 2 , COX-2 and HIF-1α were assayed by enzyme-linked immunosorbent assay or western blotting. Treatment with the AGNE at 10, 20, and 40 mg/kg alleviated weight loss, decreased disease activity index scores, and reduced colon shortening in mice with DSS-induced UC. AGNE inhibited the production of IL-6 and TNF-α in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1α and the increased production of PGE 2 in colon tissue were observed in mice with DSS-induced UC. Additionally, histological damage was also alleviated by AGNE treatment. The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Berberine inhibits macrophage M1 polarization via AKT1/SOCS1/NF-κB signaling pathway to protect against DSS-induced colitis.

PubMed

Liu, Yunxin; Liu, Xiang; Hua, Weiwei; Wei, Qingyan; Fang, Xianjun; Zhao, Zheng; Ge, Chun; Liu, Chao; Chen, Chen; Tao, Yifu; Zhu, Yubing

2018-04-01

Berberine has been reported to have protective effects in colitis treatment. However, the detailed mechanisms remain unclear. Herein, we demonstrated that berberine could protect against dextran sulfate sodium (DSS)-induced colitis in mice by regulating macrophage polarization. In the colitis mouse model, berberine ameliorated DSS-induced colon shortening and colon tissue injury. Moreover, berberine-treated mice showed significant reduction in the disease activity index (DAI), pro-inflammatory cytokines expression and macrophages infiltration compared with the DSS-treated mice. Notably, berberine significantly reduced the percentage of M1 macrophages. In vitro analysis also confirmed the inhibitory effects of berberine on macrophages M1 polarization in RAW267.4 cells. Further investigation showed that berberine promoted AKT1 expression in mRNA and protein level. Silence of AKT1 abolished the inhibitory effect of berberine on macrophages M1 polarization. The berberine-induced AKT1 expression promoted suppressers of cytokine signaling (SOCS1) activation, which inhibited nuclear factor-kappa B (NF-κB) phosphorylation. In addition, we also found that berberine activated AKT1/SOCS1 signaling pathway but inhibited p65 phosphorylation in macrophages in vivo. Therefore, we concluded that berberine played a regulatory role in macrophages M1 polarization in DSS-induced colitis via AKT1/SOCS1/NF-κB signaling pathway. This unexpected property of berberine may provide a potential explanation for its protective effects in colitis treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Differential intestinal anti-inflammatory effects of Lactobacillus fermentum and Lactobacillus salivarius in DSS mouse colitis: impact on microRNAs expression and microbiota composition.

PubMed

Rodríguez-Nogales, Alba; Algieri, Francesca; Garrido-Mesa, Jose; Vezza, Teresa; Utrilla, M Pilar; Chueca, Natalia; Garcia, Federico; Olivares, Mónica; Rodríguez-Cabezas, M Elena; Gálvez, Julio

2017-11-01

To compare the intestinal anti-inflammatory effects of two probiotics Lactobacillus fermentum and Lactobacillus salivarius in mouse colitis, focusing on their impact on selected miRNAs and microbiota composition. Male C57BL/6J mice were randomly assigned to four groups (n = 10): non-colitic, DSS colitic and two colitic groups treated with probiotics (5 × 10 8 CFU/mouse/day). Both probiotics ameliorated macroscopic colonic damage. They improved the colonic expression of markers involved in the immune response, and the expression of miR-155 and miR-223. L. fermentum also restored miR-150 and miR-143 expression, also linked to the preservation of the intestinal barrier function. Besides, these beneficial effects were associated with the amelioration of the microbiota dysbiosis and a recovery of the SCFAs- and lactic acid-producing bacterial populations, although only L. fermentum improved Chao richness, Pielou evenness and Shannon diversity. Moreover, L. fermentum also restored the Treg cell population in MLNs and the Th1/Th2 cytokine balance. Both probiotics exerted intestinal anti-inflammatory effects in DSS-mouse colitis, maybe due to their ability to restore the intestinal microbiota homeostasis and modulate the immune response. L. fermentum showed a greater beneficial effect compared to L. salivarius, which makes it more interesting for future studies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Berberine ameliorates chronic relapsing dextran sulfate sodium-induced colitis in C57BL/6 mice by suppressing Th17 responses.

PubMed

Li, Yan-Hong; Xiao, Hai-Tao; Hu, Dong-Dong; Fatima, Sarwat; Lin, Cheng-Yuan; Mu, Huai-Xue; Lee, Nikki P; Bian, Zhao-Xiang

2016-08-01

Ulcerative colitis (UC) is an increasingly common condition particularly in developed countries. The lack of satisfactory treatment has fueled the search for alternative therapeutic strategies. In recent studies, berberine, a plant alkaloid with a long history of medicinal use in Chinese medicine, has shown beneficial effects against animal models of acute UC. However, UC usually presents as a chronic condition with frequent relapse in patients. How berberine will act on chronic UC remains unclear. In the present study, we adopted dextran sulfate sodium (DSS)-induced chronic relapsing colitis model to assess the ameliorating activity of berberine. Colitis was induced by two cycles of 2.0% DSS for five days followed by 14days of drinking water plus a third cycle consisting of DSS only for five days. The colitis mice were orally administered 20mg/kg berberine from day 13 onward for 30days and monitored daily. The body weight, stool consistency, and stool bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and samples were collected and subjected to histological, RT-qPCR, Western blot, and LC-MS analyses. Lymphocytes were isolated from spleens and mesenteric lymph nodes (MLN) and cultured for flow cytometry analysis of IL-17 secretion from CD4(+) cells and the Th17 cell differentiation. Results showed that berberine significantly ameliorated the DAI, colon shortening, colon tissue injury, and reduction of colonic expression of tight junction (TJ) protein ZO-1 and occludin of colitis mice. Notably, berberine treatment pronouncedly reduced DSS-upregulated Th17-related cytokine (IL-17 and ROR-γt) mRNAs in the colon. Furthermore, the mRNA expression of IL-6 and IL-23, and the phosphorylation of STAT3 in colon tissues from DSS-treated mice were pronouncedly inhibited by berberine. Moreover, the up-regulation of IL-17 secretion from CD4(+) cells of spleens and MLNs caused by DSS were significantly reversed by berberine treatment. Furthermore, Th17 cell differentiation from naive CD4(+) cells isolated from above DSS colitis mice were suppressed by berberine in a concentration-dependent manner. In summary, we demonstrated for the first time that berberine reduced the severity of chronic relapsing DSS-induced colitis by suppressing Th17 responses. The demonstration of activity in this mouse model supports the possibility of clinical efficacy of berberine in treating chronic UC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mice deficient in Muc4 are resistant to experimental colitis and colitis-associated colorectal cancer.

PubMed

Das, S; Rachagani, S; Sheinin, Y; Smith, L M; Gurumurthy, C B; Roy, H K; Batra, S K

2016-05-19

MUC4, a large transmembrane mucin normally expressed in the small and large intestine, is differentially expressed during inflammatory and malignant conditions of the colon. However, the expression pattern and the role of MUC4 in colitis and colorectal cancer (CRC) are inconclusive. Therefore, the aim of this study was to understand the role of Muc4 during inflammatory and malignant conditions of the colon. Here, we generated Muc4(-/-) mice and addressed its role in colitis and colitis-associated CRC using dextran sodium sulfate (DSS) and azoxymethane (AOM)-DSS experimental models, respectively. Muc4(-/-) mice were viable, fertile with no apparent defects. Muc4(-/-) mice displayed increased resistance to DSS-induced colitis compared with wild-type (WT) littermates that was evaluated by survival rate, body weight loss, diarrhea and fecal blood score, and histological score. Reduced infiltration of inflammatory cells, that is, CD3(+) lymphocytes and F4/80(+) macrophages was observed in the inflamed mucosa along with reduction in the mRNA levels of inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α and anti-microbial genes Lysozyme M and SLPI in the colon of Muc4(-/-) mice compared with WT littermates. Compensatory upregulation of Muc2 and Muc3 mucins under basal and DSS treatment conditions partly explains the resistance observed in Muc4(-/-) mice. Accordingly, Muc4(-/-) mice exhibited significantly reduced tumor burden compared with WT mice assessed in a colitis-induced tumor model using AOM/DSS. An increased percentage of Ki67(+) nuclei was observed in the tumors from WT compared with Muc4(-/-) mice suggesting Muc4 to be critical in intestinal cell proliferation during tumorigenesis. Taken together, we conclusively demonstrate for the first time the role of Muc4 in driving intestinal inflammation and inflammation-associated tumorigenesis using a novel Muc4(-/-) mouse model.

Mice deficient in Muc4 are resistant to experimental colitis and colitis-associated colorectal cancer

PubMed Central

Das, S; Rachagani, S; Sheinin, Y; Smith, LM; Gurumurthy, CB; Roy, HK; Batra, SK

2017-01-01

MUC4, a large transmembrane mucin normally expressed in the small and large intestine, is differentially expressed during inflammatory and malignant conditions of the colon. However, the expression pattern and the role of MUC4 in colitis and colorectal cancer (CRC) are inconclusive. Therefore, the aim of this study was to understand the role of Muc4 during inflammatory and malignant conditions of the colon. Here, we generated Muc4−/− mice and addressed its role in colitis and colitis-associated CRC using dextran sodium sulfate (DSS) and azoxymethane (AOM)-DSS experimental models, respectively. Muc4−/− mice were viable, fertile with no apparent defects. Muc4−/− mice displayed increased resistance to DSS-induced colitis compared with wild-type (WT) littermates that was evaluated by survival rate, body weight loss, diarrhea and fecal blood score, and histological score. Reduced infiltration of inflammatory cells, that is, CD3+ lymphocytes and F4/80+ macrophages was observed in the inflamed mucosa along with reduction in the mRNA levels of inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α and anti-microbial genes Lysozyme M and SLPI in the colon of Muc4−/− mice compared with WT littermates. Compensatory upregulation of Muc2 and Muc3 mucins under basal and DSS treatment conditions partly explains the resistance observed in Muc4−/− mice. Accordingly, Muc4−/− mice exhibited significantly reduced tumor burden compared with WT mice assessed in a colitis-induced tumor model using AOM/DSS. An increased percentage of Ki67+ nuclei was observed in the tumors from WT compared with Muc4−/− mice suggesting Muc4 to be critical in intestinal cell proliferation during tumorigenesis. Taken together, we conclusively demonstrate for the first time the role of Muc4 in driving intestinal inflammation and inflammation-associated tumorigenesis using a novel Muc4−/− mouse model. PMID:26364605

Curcumin Inhibits STAT3 Signaling in the Colon of Dextran Sulfate Sodium-treated Mice

PubMed Central

Yang, Joon-Yeop; Zhong, Xiancai; Yum, Hye-Won; Lee, Hyung-Jun; Kundu, Joydeb Kumar; Na, Hye-Kyung; Surh, Young-Joon

2013-01-01

Turmeric (Curcuma longa L., Zingiberaceae) has a long history of use in medicine for the treatment of inflammatory conditions. One of the major constituents of turmeric is curcumin (diferuloylmethane), which is responsible for its characteristic yellow color. In the present study, we have examined the chemoprotective effects of curcuminon dextran sulfate sodium (DSS)-induced mouse colitis. For this purpose, we pre-treated male ICR mice with curcumin (0.1 or 0.25 mmol/kg in 0.05% carboxymethyl cellulose) by gavage for a week and then co-treated the animals with curcumin by gavage and 3% DSS in drinking water for another 7 days. Our study revealed that administration of curcumin significantly attenuated the severity of DSS-induced colitis and STAT3 signaling in mouse colon. The levels of the cell cycle regulators CDK4 and cylinD1 were significantly reduced by curcumin administration. Moreover, the expression of p53, which is an upstream regulator of the CDK4-cylinD1 complex, was inhibited by curcumin treatment. PMID:25337545

R-Spondins Are Expressed by the Intestinal Stroma and are Differentially Regulated during Citrobacter rodentium- and DSS-Induced Colitis in Mice.

PubMed

Kang, Eugene; Yousefi, Mitra; Gruenheid, Samantha

2016-01-01

The R-spondin family of proteins has recently been described as secreted enhancers of β-catenin activation through the canonical Wnt signaling pathway. We previously reported that Rspo2 is a major determinant of susceptibility to Citrobacter rodentium-mediated colitis in mice and recent genome-wide association studies have revealed RSPO3 as a candidate Crohn's disease-specific inflammatory bowel disease susceptibility gene in humans. However, there is little information on the endogenous expression and cellular source of R-spondins in the colon at steady state and during intestinal inflammation. RNA sequencing and qRT-PCR were used to assess the expression of R-spondins at steady state and in two mouse models of colonic inflammation. The cellular source of R-spondins was assessed in specific colonic cell populations isolated by cell sorting. Data mining from publicly available datasets was used to assess the expression of R-spondins in the human colon. At steady state, colonic expression of R-spondins was found to be exclusive to non-epithelial CD45- lamina propria cells, and Rspo3/RSPO3 was the most highly expressed R-spondin in both mouse and human colon. R-spondin expression was found to be highly dynamic and differentially regulated during C. rodentium infection and dextran sodium sulfate (DSS) colitis, with notably high levels of Rspo3 expression during DSS colitis, and high levels of Rspo2 expression during C. rodentium infection, specifically in susceptible mice. Our data are consistent with the hypothesis that in the colon, R-spondins are expressed by subepithelial stromal cells, and that Rspo3/RSPO3 is the family member most implicated in colonic homeostasis. The differential regulation of the R-spondins in different models of intestinal inflammation indicate they respond to specific pathogenic and inflammatory signals that differ in the two models and provides further evidence that this family of proteins plays a key role in linking intestinal inflammation and homeostasis.

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

PubMed

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

2017-01-01

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

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

PubMed

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

2018-04-01

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

Role of glycogen synthase kinase-3β and PPAR-γ on epithelial-to-mesenchymal transition in DSS-induced colorectal fibrosis.

PubMed

Di Gregorio, Jacopo; Sferra, Roberta; Speca, Silvia; Vetuschi, Antonella; Dubuquoy, Caroline; Desreumaux, Pierre; Pompili, Simona; Cristiano, Loredana; Gaudio, Eugenio; Flati, Vincenzo; Latella, Giovanni

2017-01-01

Intestinal fibrosis is characterized by abnormal production and deposition of extracellular matrix (ECM) proteins by activated myofibroblasts. The main progenitor cells of activated myofibroblasts are the fibroblasts and the epithelial cells, the latter through the epithelial-mesenchymal transition (EMT). To evaluate the action of the new PPAR-γ modulator, GED-0507-34 Levo (GED) on the expression of EMT associated and regulatory proteins such as TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, and GSK-3β, in a mouse model of DSS-induced intestinal fibrosis. Chronic colitis and fibrosis were induced by oral administration of 2.5% DSS (w/v) for 6 weeks. GW9662 (GW), a selective PPAR-γ inhibitor, was also administered by intraperitoneal injection at the dose of 1 mg/kg/day combined with GED treatment. All drugs were administered at the beginning of the second cycle of DSS (day 12). 65 mice were randomly divided into five groups (H2O as controls n = 10, H2O+GED n = 10, DSS n = 15, DSS+GED n = 15, DSS+GED+GW n = 15). The colon was excised for macroscopic examination and histological and morphometric analyses. The level of expression of molecules involved in EMT and fibrosis, like TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, GSK-3β and PPAR-γ, was assessed by immunohistochemistry, immunofluorescence, western blot and Real Time PCR. GED improved the DSS-induced chronic colitis and fibrosis. GED was able to reduce the expression of the main fibrosis markers (α-SMA, collagen I-III and fibronectin) as well as the pivotal pro-fibrotic molecules IL-13, TGF-β and Smad3, while it increased the anti-fibrotic PPAR-γ. All these GED effects were nullified by co-administration of GW with GED. Furthermore, GED was able to normalize the expression levels of E-cadherin and β-catenin and upregulated GSK-3β, that are all known to be involved both in EMT and fibrosis. The DSS-induced intestinal fibrosis was improved by the new PPAR-γ modulator GED-0507-34 Levo through the modulation of EMT mediators and pro-fibrotic molecules and through GSK-3β induction.

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

PubMed Central

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

2015-01-01

Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9−/− mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9−/− mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9−/− mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK−/− mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9−/− mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK. PMID:26514773

DNA methylome and transcriptome alterations and cancer prevention by curcumin in colitis-accelerated colon cancer in mice.

PubMed

Guo, Yue; Wu, Renyi; Gaspar, John M; Sargsyan, Davit; Su, Zheng-Yuan; Zhang, Chengyue; Gao, Linbo; Cheng, David; Li, Wenji; Wang, Chao; Yin, Ran; Fang, Mingzhu; Verzi, Michael P; Hart, Ronald P; Kong, Ah-Ng

2018-05-03

Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms could play an important role in the initiation and progression of colon cancer. Curcumin, a dietary phytochemical, shows promising effects in suppressing colitis-associated colon cancer in azoxymethane-dextran sulfate sodium (AOM-DSS) mice. However, the potential epigenetic mechanisms of curcumin in colon cancer remain unknown. In this study, the anticancer effect of curcumin in suppressing colon cancer in an 18-week AOM-DSS colon cancer mouse model was confirmed. We identified lists of differentially expressed and differentially methylated genes in pairwise comparisons and several pathways involved in the potential anticancer effect of curcumin. These pathways include LPS/IL-1-mediated inhibition of RXR function, Nrf2-mediated oxidative stress response, production of NO and ROS in macrophages and IL-6 signaling. Among these genes, Tnf stood out with decreased DNA CpG methylation of Tnf in the AOM-DSS group and reversal of the AOM-DSS induced Tnf demethylation by curcumin. These observations in Tnf methylation correlated with increased and decreased Tnf expression in RNA-seq. The functional role of DNA methylation of Tnf was further confirmed by in vitro luciferase transcriptional activity assay. In addition, the DNA methylation level in a group of inflammatory genes was decreased in the AOM+DSS group but restored by curcumin and was validated by pyrosequencing. This study shows for the first time epigenomic changes in DNA CpG methylation in the inflammatory response from colitis-associated colon cancer and the reversal of their CpG methylation changes by curcumin. Future clinical epigenetic studies with curcumin in inflammation-associated colon cancer would be warranted.

Functional characterization of CXCR4 in mediating the expression of protein C system in experimental ulcerative colitis

PubMed Central

Lin, Xuhong; Wang, Huichao; Li, Yuxia; Yang, Jingnan; Yang, Ruilin; Wei, Dandan; Zhang, Junjie; Yang, Desheng; Wang, Bin; Ren, Xuequn; Cheng, Guanchang

2017-01-01

The present study aimed to explore the role of CXCR4 and protein C system (PCS) in the experimental ulcerative colitis (UC). The expression of CXCR3, CCR10, and CXCR4 in dextran sulfate sodium (DSS)-induced colitis mouse model was measured by immunohistochemistry and western blot analysis. In vitro studies with microvascular endothelial cells (MVECs) were performed. The expression of endothelial protein C receptor (EPCR) and thrombomodulin (TM) were detected by RT-PCR and western blot analysis. Activities of protein C (PC), protein S (PS), activated PC (APC) were evaluated in cells pre-treated with JNK inhibitor SP600125 and c-Jun silencing. DSS mice showed up-regulated expression of CXCR4, higher macroscopic score and histological score (P<0.05), as well as elevated levels of SDF-1α (P<0.05) compared with wild type, CXCR4-/-, or CXCR4-/- +DSS mice. In DSS mice, EPCR expression was down-regulated (P<0.05), accompanied by decreased activity of PC and PS (P<0.05 or P<0.01) with an up-regulated expression of pJNK MAPK and pc-Jun (P<0.05). Moreover, the macroscopic score and histological score index, SDF-1α levels, EPCR expression, PC activity, pJNK, and pc-Jun were reversed in CXCR4-/- +DSS mice (P<0.05). In vitro, SDF-1α-induced inhibition of the PCS was blunted by SP600125 (P<0.05). Meanwhile, down-regulation of c-Jun rescued the inhibition of PCS (P<0.05). MVECs with retrovirus-mediated transfection of c-Jun demonstrated a strong trans-inactivation effect on the EPCR promoter (P<0.05). These findings suggest that CXCR4 is involved in UC pathogenesis and could be a promising therapeutic target for UC treatment. PMID:29218082

Salvia miltiorrhiza (Dan Shen) Significantly Ameliorates Colon Inflammation in Dextran Sulfate Sodium Induced Colitis

PubMed Central

Wen, Xiao-Dong; Wang, Chong-Zhi; Yu, Chunhao; Zhang, Zhiyu; Calway, Tyler; Wang, Yunwei; Li, Ping; Yuan, Chun-Su

2014-01-01

Inflammatory bowel disease increases the risks of human colorectal cancer. In this study, the effects of Salvia miltiorrhiza extract (SME) on chemically-induced colitis in a mouse model were evaluated. Chemical composition of SME was determined by HPLC analysis. A/J mice received a single injection of AOM 7.5 mg/kg. After one week, these mice received 2.5% DSS for 8 days, or DSS plus SME (25 or 50 mg/kg). DSS-induced colitis was scored with the disease activity index (DAI). Body weight and colon length were also measured. The severity of inflammatory lesions was further evaluated by colon tissue histological assessment. HPLC assay showed that the major constituents in the tested SME were danshensu, protocatechuic aldehyde, salvianolic acid D and salvianolic acid B. In the model group, the DAI score reached its highest level on Day 8, while the SME group on both doses showed a significantly reduced DAI score (both P < 0.01). As an objective index of the severity of inflammation, colon length was reduced significantly from the vehicle group to model group. Treatment with 25 and 50 mg/kg of SME inhibited the reduction of colon in a dose-related manner (P < 0.05 and P < 0.01, respectively). SME groups also significantly reduced weight reduction (P < 0.05). Colitis histological data supported the pharmacological observations. Thus, Salvia miltiorrhiza could be a promising candidate in preventing and treating colitis and in reducing the risks of inflammation-associated colorectal cancer. PMID:24117071

Salvia miltiorrhiza (dan shen) significantly ameliorates colon inflammation in dextran sulfate sodium induced colitis.

PubMed

Wen, Xiao-Dong; Wang, Chong-Zhi; Yu, Chunhao; Zhang, Zhiyu; Calway, Tyler; Wang, Yunwei; Li, Ping; Yuan, Chun-Su

2013-01-01

Inflammatory bowel disease increases the risks of human colorectal cancer. In this study, the effects of Salvia miltiorrhiza extract (SME) on chemically-induced colitis in a mouse model were evaluated. Chemical composition of SME was determined by HPLC analysis. A/J mice received a single injection of AOM 7.5 mg/kg. After one week, these mice received 2.5% DSS for eight days, or DSS plus SME (25 or 50 mg/kg). DSS-induced colitis was scored with the disease activity index (DAI). Body weight and colon length were also measured. The severity of inflammatory lesions was further evaluated by colon tissue histological assessment. HPLC assay showed that the major constituents in the tested SME were danshensu, protocatechuic aldehyde, salvianolic acid D, and salvianolic acid B. In the model group, the DAI score reached its highest level on Day 8, while the SME group on both doses showed a significantly reduced DAI score (both p < 0.01). As an objective index of the severity of inflammation, colon length was significantly shorter in the model group than the vehicle group. Treatment with 25 and 50 mg/kg of SME inhibited the shortening of colon in a dose-related manner (p < 0.05 and p < 0.01, respectively). SME groups also significantly reduced weight reduction (p < 0.05). Colitis histological data supported the pharmacological observations. Thus, Salvia miltiorrhiza could be a promising candidate in preventing and treating colitis and in reducing the risks of inflammation-associated colorectal cancer.

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

PubMed Central

2018-01-01

BACKGROUND/OBJECTIVES The objective of this study was to investigate the effects of vitamin C on inflammation, tumor development, and dysbiosis of intestinal microbiota in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced inflammation-associated early colon cancer mouse model. MATERIALS/METHODS Male BALB/c mice were injected intraperitoneally with AOM [10 mg/kg body weight (b.w)] and given two 7-d cycles of 2% DSS drinking water with a 14 d inter-cycle interval. Vitamin C (60 mg/kg b.w. and 120 mg/kg b.w.) was supplemented by gavage for 5 weeks starting 2 d after the AOM injection. RESULTS The vitamin C treatment suppressed inflammatory morbidity, as reflected by disease activity index (DAI) in recovery phase and inhibited shortening of the colon, and reduced histological damage. In addition, vitamin C supplementation suppressed mRNA levels of pro-inflammatory mediators and cytokines, including cyclooxygenase-2, microsomal prostaglandin E synthase-2, tumor necrosis factor-α, Interleukin (IL)-1β, and IL-6, and reduced expression of the proliferation marker, proliferating cell nuclear antigen, compared to observations of AOM/DSS animals. Although the microbial composition did not differ significantly between the groups, administration of vitamin C improved the level of inflammation-related Lactococcus and JQ084893 to control levels. CONCLUSION Vitamin C treatment provided moderate suppression of inflammation, proliferation, and certain inflammation-related dysbiosis in a murine model of colitis associated-early colon cancer. These findings support that vitamin C supplementation can benefit colonic health. Long-term clinical studies with various doses of vitamin C are warranted. PMID:29629026

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

PubMed Central

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

2015-01-01

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal (GI) tract, and currently no curative treatment available. Mangiferin, a natural glucosylxanthone mainly from the fruit, leaves and stem bark of the mango tree, has strong anti-inflammatory activity. We sought to investigate whether mangiferin attenuates inflammation in a mouse model of chemically induced IBD. Pre-administration of mangiferin significantly attenuated dextran sulfate sodium (DSS)-induced body weight loss, diarrhea, colon shortening and histological injury, which correlated with the decline in the activity of myeloperoxidase (MPO) and the level of tumor necrosis factor-α (TNF-α) in the colon. DSS-induced degradation of inhibitory κBα (IκBα) and the phosphorylation of nuclear factor-kappa B (NF-κB) p65 as well as the mRNA expression of pro-inflammatory mediators (inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), TNF-α, interleukin-1β (IL-1β) and IL-6) in the colon were also downregulated by mangiferin treatment. Additionally, the phosphorylation/activation of DSS-induced mitogen-activated protein kinase (MAPK) proteins was also inhibited by mangiferin treatment. In accordance with the in vivo results, mangiferin exposure blocked TNF-α-stimulated nuclear translocation of NF-κB in RAW264.7 mouse macrophage cells. Transient transfection gene reporter assay performed in TNF-α-stimulated HT-29 human colorectal adenocarcinoma cells indicated that mangiferin inhibits NF-κB transcriptional activity in a dose-dependent manner. The current study clearly demonstrates a protective role for mangiferin in experimental IBD through NF-κB and MAPK signaling inhibition. Since mangiferin is a natural compound with little toxicity, the results may contribute to the effective utilization of mangiferin in the treatment of human IBD. PMID:25194678

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

PubMed

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

2014-02-01

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

R-Spondins Are Expressed by the Intestinal Stroma and are Differentially Regulated during Citrobacter rodentium- and DSS-Induced Colitis in Mice

PubMed Central

Kang, Eugene; Yousefi, Mitra; Gruenheid, Samantha

2016-01-01

The R-spondin family of proteins has recently been described as secreted enhancers of β-catenin activation through the canonical Wnt signaling pathway. We previously reported that Rspo2 is a major determinant of susceptibility to Citrobacter rodentium-mediated colitis in mice and recent genome-wide association studies have revealed RSPO3 as a candidate Crohn’s disease-specific inflammatory bowel disease susceptibility gene in humans. However, there is little information on the endogenous expression and cellular source of R-spondins in the colon at steady state and during intestinal inflammation. RNA sequencing and qRT-PCR were used to assess the expression of R-spondins at steady state and in two mouse models of colonic inflammation. The cellular source of R-spondins was assessed in specific colonic cell populations isolated by cell sorting. Data mining from publicly available datasets was used to assess the expression of R-spondins in the human colon. At steady state, colonic expression of R-spondins was found to be exclusive to non-epithelial CD45- lamina propria cells, and Rspo3/RSPO3 was the most highly expressed R-spondin in both mouse and human colon. R-spondin expression was found to be highly dynamic and differentially regulated during C. rodentium infection and dextran sodium sulfate (DSS) colitis, with notably high levels of Rspo3 expression during DSS colitis, and high levels of Rspo2 expression during C. rodentium infection, specifically in susceptible mice. Our data are consistent with the hypothesis that in the colon, R-spondins are expressed by subepithelial stromal cells, and that Rspo3/RSPO3 is the family member most implicated in colonic homeostasis. The differential regulation of the R-spondins in different models of intestinal inflammation indicate they respond to specific pathogenic and inflammatory signals that differ in the two models and provides further evidence that this family of proteins plays a key role in linking intestinal inflammation and homeostasis. PMID:27046199

Alterations in biomechanical properties and microstructure of colon wall in early-stage experimental colitis.

PubMed

Gong, Xiaohui; Xu, Xiaojuan; Lin, Sisi; Cheng, Yu; Tong, Jianhua; Li, Yongyu

2017-08-01

The aim of the current study was to investigate the effects of early-stage dextran sodium sulfate (DSS)-induced mouse colitis on the biomechanical properties and microstructure of colon walls. In the present study, colitis was induced in 8-week-old mice by the oral administration of DSS, and then 10 control and 10 experimental colitis samples were harvested. Uniaxial tensile tests were performed to measure the ultimate tensile strength and ultimate stretches of colon tissues. In addition, histological investigations were performed to characterize changes in the microstructure of the colon wall following treatment. The results revealed that the ultimate tensile stresses were 232±33 and 183±25 kPa for the control and DSS groups, respectively (P=0.001). Ultimate stretches at rupture for the control and DSS groups were 1.43±0.04 and 1.51±0.06, respectively (P=0.006). However, there was no statistically significant difference in tissue stiffness between the two groups. Histological analysis demonstrated high numbers of inflammatory cells infiltrated into the stroma in the DSS group, leading to significant submucosa edema. Hyperplasia was also identified in the DSS-treated submucosa, causing a disorganized microstructure within the colon wall. Furthermore, a large number of collagen fibers in the DSS-treated muscular layer were disrupted, and fiber bundles were thinner when compared with the control group. In conclusion, early-stage experimental colitis alters the mechanical properties and microstructural characteristics of the colon walls, further contributing to tissue remodeling in the pathological process.

Targeted delivery of vitamin D to the colon using β-glucuronides of vitamin D: therapeutic effects in a murine model of inflammatory bowel disease

PubMed Central

Koszewski, Nicholas J.; Haynes, Joseph S.; Horst, Ronald L.

2012-01-01

1,25-Dihydroxyvitamin D3 [1,25(OH)2D] has been shown to inhibit development of dextran sodium sulfate (DSS)-induced colitis in mice but can also cause hypercalcemia. The aim of this study was to evaluate whether β-glucuronides of vitamin D could deliver 1,25(OH)2D to the colon to ameliorate colitis while reducing the risk of hypercalcemia. Initial studies demonstrated that bacteria residing in the lower intestinal tract were capable of liberating 1,25(OH)2D from 1,25-dihydroxyvitamin D3-25-β-glucuronide [β-gluc-1,25(OH)2D]. We also determined that a much greater upregulation of the vitamin D-dependent 24-hydroxylase gene (Cyp24) was induced in the colon by treatment of mice with an oral dose of β-gluc-1,25(OH)2D than 1,25(OH)2D, demonstrating targeted delivery of 1,25(OH)2D to the colon. We then tested β-glucuronides of vitamin D in the mouse DSS colitis model in two studies. In mice receiving DSS dissolved in distilled water and treated with 1,25(OH)2D or β-gluc-1,25(OH)2D, severity of colitis was reduced. Combination of β-gluc-1,25(OH)2D with 25-hydroxyvitamin D3-25-β-glucuronide [β-gluc-25(OH)D] resulted in the greatest reduction of colitis lesions and symptoms in DSS-treated mice. Plasma calcium concentrations were lower in mice treated with β-gluc-1,25(OH)2D alone or in combination with β-gluc-25(OH)D than in mice treated with 1,25(OH)2D, which were hypercalcemic at the time of death. β-Glucuronides of vitamin D compounds can deliver 1,25(OH)2D to the lower intestine and can reduce symptoms and lesions of acute colitis in this model. PMID:22114117

The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis

PubMed Central

Cardoso, Ana; Gil Castro, Antonio; Martins, Ana Catarina; Carriche, Guilhermina M.; Murigneux, Valentine; Castro, Isabel; Cumano, Ana; Vieira, Paulo; Saraiva, Margarida

2018-01-01

Inflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyperinflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL)-10, as shown in mice and humans. Indeed, IL-10 signaling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10-mediated protection during chemical colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 overexpression (pMT-10), described here, we show that mice preconditioned with IL-10 for 8 days before dextran sulfate sodium (DSS) administration developed a milder colitic phenotype. In IL-10-induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection. PMID:29545807

Chemopreventive effects of standardized ethanol extract from the aerial parts of Artemisia princeps Pampanini cv. Sajabal via NF-κB inactivation on colitis-associated colon tumorigenesis in mice.

PubMed

Chung, Kyung-Sook; Choi, Hye-Eun; Shin, Ji-Sun; Cho, Eu-Jin; Cho, Young-Wuk; Choi, Jung-Hye; Baek, Nam-In; Lee, Kyung-Tae

2015-01-01

Chronic inflammation is an underlying risk factor of colon cancer, and NF-κB plays a critical role in the development of inflammation-associated colon cancer in an AOM/DSS mouse model. The aim of this study was to determine whether the standardized ethanol extract obtained from the aerial parts of Artemisia princeps Pampanini cv. Sajabal (EAPP) is effective at preventing inflammation-associated colon cancer, and if so, to identify the signaling pathways involved. In the present study, protective efficacy of EAPP on tumor formation and the infiltrations of monocytes and macrophages in colons of an AOM/DSS mouse model were evaluated. It was found that colitis and tumor burdens showed statistically meaningful improvements after EAPP administration. Furthermore, these improvements were accompanied by a reduction in NF-κB activity and in the levels of NF-κB-dependent pro-survival proteins, that is, survivin, cFLIP, XIAP, and Bcl-2. In vitro, EAPP significantly reduced NF-κB activation and the levels of IL-1β and IL-8 mRNA and pro-survival proteins in HT-29 and HCT-116 colon cancer cells. Furthermore, EAPP caused caspase-dependent apoptosis. Based on these results, the authors suggest EAPP suppresses inflammatory responses and induces apoptosis partly via NF-κB inactivation, and that EAPP could be useful for the prevention of colitis-associated tumorigenesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

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

2010-09-07

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

Maillard reaction products from highly heated food prevent mast cell number increase and inflammation in a mouse model of colitis.

PubMed

Al Amir, Issam; Dubayle, David; Héron, Anne; Delayre-Orthez, Carine; Anton, Pauline M

2017-12-01

Links between food and inflammatory bowel diseases (IBDs) are often suggested, but the role of food processing has not been extensively studied. Heat treatment is known to cause the loss of nutrients and the appearance of neoformed compounds such as Maillard reaction products. Their involvement in gut inflammation is equivocal, as some may have proinflammatory effects, whereas other seem to be protective. As IBDs are associated with the recruitment of immune cells, including mast cells, we raised the hypothesis that dietary Maillard reaction products generated through heat treatment of food may limit the colitic response and its associated recruitment of mast cells. An experimental model of colitis was used in mice submitted to mildly and highly heated rodent food. Adult male mice were divided in 3 groups and received nonheated, mildly heated, or highly heated chow during 21 days. In the last week of the study, each group was split into 2 subgroups, submitted or not (controls) to dextran sulfate sodium (DSS) colitis. Weight variations, macroscopic lesions, colonic myeloperoxidase activity, and mucosal mast cell number were evaluated at the end of the experiment. Only highly heated chow significantly prevented DSS-induced weight loss, myeloperoxidase activity, and mast cell number increase in the colonic mucosa of DSS-colitic mice. We suggest that Maillard reaction products from highly heated food may limit the occurrence of inflammatory phases in IBD patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential role for ET-2 acting through ETA receptors in experimental colitis in mice.

PubMed

Claudino, R F; Leite, D F; Bento, A F; Chichorro, J G; Calixto, J B; Rae, G A

2017-02-01

This study attempted to clarify the roles of endothelins and mechanisms associated with ET A /ET B receptors in mouse models of colitis. Colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 1.5 mg/animal) or dextran sulfate sodium (DSS, 3%). After colitis establishment, mice received Atrasentan (ET A receptor antagonist, 10 mg/kg), A-192621 (ET B receptor antagonist, 20 mg/kg) or Dexamethasone (1 mg/kg) and several inflammatory parameters were assessed, as well as mRNA levels for ET-1, ET-2 and ET receptors. Atrasentan treatment ameliorates TNBS- and DSS-induced colitis. In the TNBS model was observed reduction in macroscopic and microscopic score, colon weight, neutrophil influx, IL-1β, MIP-2 and keratinocyte chemoattractant (KC) levels, inhibition of adhesion molecules expression and restoration of IL-10 levels. However, A192621 treatment did not modify any parameter. ET-1 and ET-2 mRNA was decreased 24 h, but ET-2 mRNA was markedly increased at 48 h after TNBS. ET-2 was able to potentiate LPS-induced KC production in vitro. ET A and ET B receptors mRNA were increased at 24, 48 and 72 h after colitis induction. Atrasentan treatment was effective in reducing the severity of colitis in DSS- and TNBS-treated mice, suggesting that ET A receptors might be a potential target for inflammatory bowel diseases.

Protective effect of Lagerstroemia speciosa against dextran sulfate sodium induced ulcerative colitis in C57BL/6 mice.

PubMed

Chaudhary, Ghanshyam; Mahajan, Umesh B; Goyal, Sameer N; Ojha, Shreesh; Patil, Chandragouda R; Subramanya, Sandeep B

2017-01-01

The protective effect of methanolic extract of Lagerstroemia speciosaleaves (LS) was evaluated against dextran sulfate sodium (DSS) induced ulcerative colitis in C57BL/6 mice. The administration of DSS (2.5% in drinking water ad libitum) in C57BL/6 mice induced ulcerative colitis in 7 days. The LS was orally administered for 7 days at daily doses of 100 and 200 mg/kg. At the end of 7 days of treatment the animals were sacrificed, colonic tissues were removed and processed for further analysis of oxidative stress, and histopathology. In DSS treated mice the oxidative stress markers were elevated compared to controls. There was also significant reduction in the anti-oxidant defense levels marked by reduced cellular glutathione, catalase, and superoxide dismutase. The DSS-induced damage to the colon epithelium was evident from a significant increase in the lipid peroxidation. The histology of colon sections revealed inflammatory changes and marked impairment in the integrity of the mucosal lining with inflammatory changes. Both the doses of LS significantly prevented DSS-induced inflammatory and ulcerative damages of the colon, reduced lipid peroxidation and also restored the levels of innate antioxidants in the colon tissue. These findings indicate the protective effects of LS against the DSS-induced inflammatory and oxidative damage in the mouse colon. Further investigation involving bioactivity guided fractionation of the LS can yield potent constituent which may have a significant role in the treatment of inflammatory bowel disease and ulcerative colitis.

Induction of colitis in young rats by dextran sulfate sodium.

PubMed

Vicario, María; Crespí, Mar; Franch, Angels; Amat, Concepció; Pelegrí, Carme; Moretó, Miquel

2005-01-01

Models using dextran sulfate sodium (DSS) to induce experimental colitis in rodents have been performed mostly in adult animals. For this reason, we aimed to develop a model of colitis in young rats. DSS was administered to 30-day-old rats at concentrations ranging from 0.5 to 5% in drinking water. Young rats were remarkably sensitive to DSS since clinical symptoms rapidly rose with 5% DSS and most animals died after the fifth day. With 1 and 2% DSS, the severity of mucosal lesions was also high on day 7, the animals showing leukocytosis and anemia. At 0.5% DSS, leukocytosis and mild colonic lesions were induced. This concentration of DSS significantly increased myeloperoxidase activity and goblet cell number in the colon, indicating mucosal inflammation. Since food consumption was not reduced by 0.5% DSS, we suggest that this protocol can be used to study the effects of dietary supplements on intestinal inflammatory processes.

Induction of Colitis in Young Rats by Dextran Sulfate Sodium.

PubMed

Vicario, María; Crespí, Mar; Franch, Àngels; Amat, Concepció; Pelegrí, Carme; Moretó, Miquel

2005-01-01

Models using dextran sulfate sodium (DSS) to induce experimental colitis in rodents have been performed mostly in adult animals. For this reason, we aimed to develop a model of colitis in young rats. DSS was administered to 30-day-old rats at concentrations ranging from 0.5 to 5% in drinking water. Young rats were remarkably sensitive to DSS since clinical symptoms rapidly rose with 5% DSS and most animals died after the fifth day. With 1 and 2% DSS, the severity of mucosal lesions was also high on day 7, the animals showing leukocytosis and anemia. At 0.5% DSS, leukocytosis and mild colonic lesions were induced. This concentration of DSS significantly increased myeloperoxidase activity and goblet cell number in the colon, indicating mucosal inflammation. Since food consumption was not reduced by 0.5% DSS, we suggest that this protocol can be used to study the effects of dietary supplements on intestinal inflammatory processes.

Behavioral and molecular processing of visceral pain in the brain of mice: impact of colitis and psychological stress

PubMed Central

Jain, Piyush; Hassan, Ahmed M.; Koyani, Chintan N.; Mayerhofer, Raphaela; Reichmann, Florian; Farzi, Aitak; Schuligoi, Rufina; Malle, Ernst; Holzer, Peter

2015-01-01

Gastrointestinal disorders with abdominal pain are associated with central sensitization and psychopathologies that are often exacerbated by stress. Here we investigated the impact of colitis induced by dextran sulfate sodium (DSS) and repeated water avoidance stress (WAS) on spontaneous and nociception-related behavior and molecular signaling in the mouse brain. DSS increased the mechanical pain sensitivity of the abdominal skin while both WAS and DSS enhanced the mechanical and thermal pain sensitivity of the plantar skin. These manifestations of central sensitization were associated with augmented c-Fos expression in spinal cord, thalamus, hypothalamus, amygdala and prefrontal cortex. While WAS stimulated phosphorylation of mitogen-activated protein kinase (MAPK) p42/44, DSS activated another signaling pathway, both of which converged on c-Fos. The DSS- and WAS-induced hyperalgesia in the abdominal and plantar skin and c-Fos expression in the brain disappeared when the mice were subjected to WAS+DSS treatment. Intrarectal allyl isothiocyanate (AITC) evoked aversive behavior (freezing, reduction of locomotion and exploration) in association with p42/44 MAPK and c-Fos activation in spinal cord and brain. These effects were inhibited by morphine, which attests to their relationship with nociception. DSS and WAS exerted opposite effects on AITC-evoked p42/44 MAPK and c-Fos activation, which indicates that these transduction pathways subserve different aspects of visceral pain processing in the brain. In summary, behavioral perturbations caused by colitis and psychological stress are associated with distinct alterations in cerebral signaling. These findings provide novel perspectives on central sensitization and the sensory and emotional processing of visceral pain stimuli in the brain. PMID:26217204

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klein, Steven Karl; Determan, John C.

Dynamic System Simulation (DSS) models of fissile solution systems have been developed and verified against a variety of historical configurations. DSS techniques have been applied specifically to subcritical accelerator-driven systems using fissile solution fuels of uranium. Initial DSS models were developed in DESIRE, a specialized simulation scripting language. In order to tailor the DSS models to specifically meet needs of system designers they were converted to a Visual Studio implementation, and one of these subsequently to National Instrument’s LabVIEW for human factors engineering and operator training. Specific operational characteristics of subcritical accelerator-driven systems have been examined using a DSS modelmore » tailored to this particular class using fissile fuel.« less

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

PubMed

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

2016-02-01

Fisetin, a dietary flavonoid, is commonly found in many fruits and vegetables. Although studies indicate that fisetin has an anti-inflammatory property, little is known about its effects on intestinal inflammation. The present study investigated the effects of the fisetin on dextran sulphate sodium (DSS)-induced murine colitis, an animal model that resembles human inflammatory bowel disease. Fisetin treatment to DSS-exposed mice significantly reduced the severity of colitis and alleviated the macroscopic and microscopic signs of the disease. Moreover, fisetin reduced the levels of myeloperoxidase activity, the production of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) and the expressions of COX-2 and iNOS in the colon tissues. Further studies revealed that fisetin suppressed the activation of NF-κB (p65) by inhibiting IκBα phosphorylation and NF-κB (p65)-DNA binding activity and attenuated the phosphorylation of Akt and the p38, but not ERK and JNK MAPKs in the colon tissues of DSS-exposed mice. In addition, DSS-induced decline in reduced glutathione (GSH) and the increase in malondialdehyde (MDA) levels were significantly restored by oral fisetin. Furthermore, the results from in vitro studies showed that fisetin significantly reduced the pro-inflammatory cytokine and mediator release and suppressed the degradation and phosphorylation of IκBα with subsequent nuclear translocation of NF-κB (p65) in lipopolysaccharide (LPS)-stimulated mouse primary peritoneal macrophages. These results suggest that fisetin exerts anti-inflammatory activity via inhibition of Akt, p38 MAPK and NF-κB signaling in the colon tissues of DSS-exposed mice. Thus, fisetin may be a promising candidate as pharmaceuticals or nutraceuticals in the treatment of inflammatory bowel disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice

PubMed Central

Huang, Yan-Feng; Qu, Chang; Xu, Lie-Qiang; Su, Zi-Ren; Zeng, Hui-Fang; Zheng, Lin; Yi, Tie-Gang; Li, Hui-Lin; Chen, Jian-Ping

2018-01-01

Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage. BB might have the potential to be further developed into a promising therapeutic option in the treatment of UC. PMID:29538417

Inhibitory effects of low-dose aloe-emodin on the development of colorectal tumors in min mice.

PubMed

Shimpo, Kan; Chihara, Takeshi; Kaneko, Takaaki; Beppu, Hidehiko; Wakamatsu, Kazumasa; Shinzato, Masanori; Yukitake, Jun; Sonoda, Shigeru

2014-01-01

Aloe-emodin (AE), a natural anthraquinone compound, has been reported to exhibit anticancer activity in various cancer cell lines and anti-inflammatory effects in murine macrophages. In the present study, we investigated the cancer chemopreventive effects of AE in an Apc-deficient Min mouse model. In the first experiment, male Min mice were fed a basal diet or diets containing 5 ppm AE and 10 ppm AE for 12 weeks. The dietary administration of 5 ppm AE significantly reduced the number of colorectal tumors. In a second experiment, we investigated the effects of AE on colitis-related colon carcinogenesis in Min mouse treated with dextran sodium sulfate (DSS). Female Min mice were administered 1% DSS in their drinking water for 7 days. AE was given to mice in their diet at a dose of 5 or 50 ppm for 5 weeks. Feeding with AE significantly reduced the number of colorectal tumors. When proliferation of cells in normal-appearing colonic mucosa was assessed by monoclonal anti-rat Ki-67 antibody (MIB-5) immunohistochemistry in experiments 1 and 2, the AE treatment significantly decreased the mean MIB-5-labeling index. These results suggest that the dietary administration of low-dose AE may have chemopreventive effects against development of colorectal tumors in Min mice, possibly in part by reducing cell proliferation in colorectal mucosa.

Loss of BID Delays FASL-Induced Cell Death of Mouse Neutrophils and Aggravates DSS-Induced Weight Loss.

PubMed

Wicki, Simone; Gurzeler, Ursina; Corazza, Nadia; Genitsch, Vera; Wong, Wendy Wei-Lynn; Kaufmann, Thomas

2018-02-28

Neutrophils are key players in the early defense against invading pathogens. Due to their potent effector functions, programmed cell death of activated neutrophils has to be tightly controlled; however, its underlying mechanisms remain unclear. Fas ligand (FASL/CD95L) has been shown to induce neutrophil apoptosis, which is accelerated by the processing of the BH3-only protein BH3 interacting domain death agonist (BID) to trigger mitochondrial apoptotic events, and been attributed a regulatory role during viral and bacterial infections. Here, we show that, in accordance with previous works, mouse neutrophils underwent caspase-dependent apoptosis in response to FASL, and that this cell death was significantly delayed upon loss of BID. However, pan-caspase inhibition failed to protect mouse neutrophils from FASL-induced apoptosis and caused a switch to RIPK3-dependent necroptotic cell death. Intriguingly, such a switch was less evident in the absence of BID, particularly under inflammatory conditions. Delayed neutrophil apoptosis has been implicated in several auto-inflammatory diseases, including inflammatory bowel disease. We show that neutrophil and macrophage driven acute dextran sulfate sodium (DSS) induced colitis was slightly more aggravated in BID-deficient mice, based on significantly increased weight loss compared to wild-type controls. Taken together, our data support a central role for FASL > FAS and BID in mouse neutrophil cell death and further underline the anti-inflammatory role of BID.

Loss of BID Delays FASL-Induced Cell Death of Mouse Neutrophils and Aggravates DSS-Induced Weight Loss

PubMed Central

Wicki, Simone; Gurzeler, Ursina; Corazza, Nadia; Genitsch, Vera

2018-01-01

Neutrophils are key players in the early defense against invading pathogens. Due to their potent effector functions, programmed cell death of activated neutrophils has to be tightly controlled; however, its underlying mechanisms remain unclear. Fas ligand (FASL/CD95L) has been shown to induce neutrophil apoptosis, which is accelerated by the processing of the BH3-only protein BH3 interacting domain death agonist (BID) to trigger mitochondrial apoptotic events, and been attributed a regulatory role during viral and bacterial infections. Here, we show that, in accordance with previous works, mouse neutrophils underwent caspase-dependent apoptosis in response to FASL, and that this cell death was significantly delayed upon loss of BID. However, pan-caspase inhibition failed to protect mouse neutrophils from FASL-induced apoptosis and caused a switch to RIPK3-dependent necroptotic cell death. Intriguingly, such a switch was less evident in the absence of BID, particularly under inflammatory conditions. Delayed neutrophil apoptosis has been implicated in several auto-inflammatory diseases, including inflammatory bowel disease. We show that neutrophil and macrophage driven acute dextran sulfate sodium (DSS) induced colitis was slightly more aggravated in BID-deficient mice, based on significantly increased weight loss compared to wild-type controls. Taken together, our data support a central role for FASL > FAS and BID in mouse neutrophil cell death and further underline the anti-inflammatory role of BID. PMID:29495595

Lactobacillus acidophilus Improves Intestinal Inflammation in an Acute Colitis Mouse Model by Regulation of Th17 and Treg Cell Balance and Fibrosis Development.

PubMed

Park, Jin-Sil; Choi, Jeong Won; Jhun, JooYeon; Kwon, Ji Ye; Lee, Bo-In; Yang, Chul Woo; Park, Sung-Hwan; Cho, Mi-La

2018-03-01

Disruption of the balance among the microbiota, epithelial cells, and resident immune cells in the intestine is involved in the pathogenesis of inflammatory bowel disease (IBD). Probiotics exert protective effects against IBD, and probiotic commensal Lactobacillus species are common inhabitants of the natural microbiota, especially in the gut. To investigate the effects of Lactobacillus acidophilus on the development of IBD, L. acidophilus was administered orally in mice with dextran sodium sulfate (DSS)-induced colitis. DSS-induced damage and the therapeutic effect of L. acidophilus were investigated. Treatment with L. acidophilus attenuated the severity of DSS-induced colitis. Specifically, it suppressed proinflammatory cytokines such as interleukin (IL)-6, tumor necrosis factor-α, IL-1β, and IL-17 in the colon tissues, which are produced by T helper (Th) 17 cells. Moreover, in vitro L. acidophilus treatment directly induced T regulatory (Treg) cells and the production of IL-10, whereas the production of IL-17 was suppressed in splenocytes. In addition, we found that L. acidophilus treatment decreased the levels of α-smooth muscle actin, a marker of activated myofibroblasts, and type I collagen compared with control mice. These results suggest that L. acidophilus may be a novel treatment for IBD by modulating the balance between Th17 and Treg cells, as well as fibrosis development.

Marine Hydroquinone Zonarol Prevents Inflammation and Apoptosis in Dextran Sulfate Sodium-Induced Mice Ulcerative Colitis

PubMed Central

Noguchi, Hirotsugu; Ueda, Yuki; Kitsuyama, Ryo; Shimizu, Hiroya; Tanimoto, Akihide; Wang, Ke-Yong; Nawata, Aya; Nakayama, Toshiyuki; Sasaguri, Yasuyuki; Satoh, Takumi

2014-01-01

Background and Aim We previously identified an anti-inflammatory compound, zonarol, a hydroquinone isolated from the brown algae Dictyopteris undulata as a marine natural product. To ascertain the in vivo functions of zonarol, we examined the pharmacological effects of zonarol administration on dextran sulfate sodium (DSS)-induced inflammation in a mouse model of ulcerative colitis (UC). Our goal is to establish a safe and effective cure for inflammatory bowel disease (IBD) using zonarol. Methods and Results We subjected Slc:ICR mice to the administration of 2% DSS in drinking water for 14 days. At the same time, 5-aminosalicylic acid (5-ASA) at a dose of 50 mg/kg (positive control) and zonarol at doses of 10 and 20 mg/kg, were given orally once a day. DSS-treated animals developed symptoms similar to those of human UC, such as severe bloody diarrhea, which were evaluated by the disease activity index (DAI). Treatment with 20 mg/kg of zonarol, as well as 5-ASA, significantly suppressed the DAI score, and also led to a reduced colonic ulcer length and/or mucosal inflammatory infiltration by various immune cells, especially macrophages. Zonarol treatment significantly reduced the expression of pro-inflammatory signaling molecules, and prevented the apoptosis of intestinal epithelial cells. Finally, zonarol protected against in vitro lipopolysaccharide (LPS)-induced activation in the RAW264.7 mouse macrophage cell line. Conclusions This is the first report that a marine bioproduct protects against experimental UC via the inhibition of both inflammation and apoptosis, very similar to the standard-of-care sulfasalazine, a well-known prodrug that releases 5-ASA. We believe that the oral administration of zonarol might offer a better treatment for human IBDs than 5-ASA, or may be useful as an alternative/additive therapeutic strategy against UC, without any evidence of side effects. PMID:25409433

The Administration of Escherichia coli Nissle 1917 Ameliorates Development of DSS-Induced Colitis in Mice

PubMed Central

Rodríguez-Nogales, Alba; Algieri, Francesca; Garrido-Mesa, José; Vezza, Teresa; Utrilla, Maria P.; Chueca, Natalia; Fernández-Caballero, Jose A.; García, Federico; Rodríguez-Cabezas, Maria E.; Gálvez, Julio

2018-01-01

The beneficial effects of probiotics on immune-based pathologies such as inflammatory bowel disease (IBD) have been well reported. However, their exact mechanisms have not been fully elucidated. Few studies have focused on the impact of probiotics on the composition of the colonic microbiota. The aim of the present study was to correlate the intestinal anti-inflammatory activity of the probiotic Escherichia coli Nissle 1917 (EcN) in the dextran sodium sulfate (DSS) model of mouse colitis with the changes induced in colonic microbiota populations. EcN prevented the DSS-induced colonic damage, as evidenced by lower disease activity index (DAI) values and colonic weight/length ratio, when compared with untreated control mice. The beneficial effects were confirmed biochemically, since the probiotic treatment improved the colonic expression of different cytokines and proteins involved in epithelial integrity. In addition, it restored the expression of different micro-RNAs (miR-143, miR-150, miR-155, miR-223, and miR-375) involved in the inflammatory response that occurs in colitic mice. Finally, the characterization of the colonic microbiota by pyrosequencing showed that the probiotic administration was able to counteract the dysbiosis associated with the intestinal inflammatory process. This effect was evidenced by an increase in bacterial diversity in comparison with untreated colitic mice. The intestinal anti-inflammatory effects of the probiotic EcN were associated with an amelioration of the altered gut microbiome in mouse experimental colitis, especially when considering bacterial diversity, which is reduced in these intestinal conditions. Moreover, this probiotic has shown an ability to modulate expression levels of miRNAs and different mediators of the immune response involved in gut inflammation. This modulation could also be of great interest to understand the mechanism of action of this probiotic in the treatment of IBD.

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

PubMed

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

2014-11-01

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal (GI) tract, and currently no curative treatment is available. Mangiferin, a natural glucosylxanthone mainly from the fruit, leaves and stem bark of a mango tree, has a strong anti-inflammatory activity. We sought to investigate whether mangiferin attenuates inflammation in a mouse model of chemically induced IBD. Pre-administration of mangiferin significantly attenuated dextran sulfate sodium (DSS)-induced body weight loss, diarrhea, colon shortening and histological injury, which correlated with the decline in the activity of myeloperoxidase (MPO) and the level of tumor necrosis factor-α (TNF-α) in the colon. DSS-induced degradation of inhibitory κBα (IκBα) and the phosphorylation of nuclear factor-kappa B (NF-κB) p65 as well as the mRNA expression of pro-inflammatory mediators (inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), TNF-α, interleukin-1β (IL-1β) and IL-6) in the colon were also downregulated by mangiferin treatment. Additionally, the phosphorylation/activation of DSS-induced mitogen-activated protein kinase (MAPK) proteins was also inhibited by mangiferin treatment. In accordance with the in vivo results, mangiferin exposure blocked TNF-α-stimulated nuclear translocation of NF-κB in RAW264.7 mouse macrophage cells. Transient transfection gene reporter assay performed in TNF-α-stimulated HT-29 human colorectal adenocarcinoma cells indicated that mangiferin inhibits NF-κB transcriptional activity in a dose-dependent manner. The current study clearly demonstrates a protective role for mangiferin in experimental IBD through NF-κB and MAPK signaling inhibition. Since mangiferin is a natural compound with little toxicity, the results may contribute to the effective utilization of mangiferin in the treatment of human IBD. Copyright © 2014 Elsevier B.V. All rights reserved.

Black Raspberries Enhance Natural Killer Cell Infiltration into the Colon and Suppress the Progression of Colorectal Cancer

PubMed Central

Pan, Pan; Kang, Siwen; Wang, Youwei; Liu, Ka; Oshima, Kiyoko; Huang, Yi-Wen; Zhang, Jianying; Yearsley, Martha; Yu, Jianhua; Wang, Li-Shu

2017-01-01

Natural killer (NK) cells are an essential component of innate immunity against cancer development. Many studies have been conducted to evaluate immune-modulating effects using dietary compounds. Our laboratory has been investigating the chemopreventive potential of black raspberries (BRBs) and previously demonstrated their beneficial modulation of genetic and epigenetic biomarkers in patients with colorectal cancer (CRC). The current study investigated their potential on modulating NK cells. To avoid the excessive inflammation caused by the dextran sulfate sodium (DSS) treatment that leads to colitis, we treated the mice with overnight DSS so that it would slightly irritate the colon but still promote colon carcinogenesis with 100% incidence in both the ApcMin/+ mice and azoxymethane (AOM)-treated mice. A significant decrease of tissue-infiltrating NK cells along the progression of microadenoma-to-adenoma and adenoma-to-adenocarcinoma was observed in the ApcMin/+/DSS and AOM/DSS mice, respectively. Depletion of NK cells significantly promoted the development of CRC, suggesting a critical role of NK cells in combating CRC progression. BRBs significantly suppressed the CRC progression and increased the number of tissue-infiltrating NK cells in both mouse models. Moreover, we further determined BRBs’ effects on NK cells in the human biopsy specimens collected from our previously completed clinical trial, in which CRC patients consumed BRBs for an average of 4 weeks during a presurgical window. We observed an increased number and an enhanced cytotoxicity of NK cells by BRB intervention. The current study provides evidence that BRBs have the potential to enhance the tumor immunesurveillance of NK cells that can be beneficial in the setting of CRC prevention and treatment. PMID:28861089

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

PubMed Central

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

2010-01-01

AIM: To analyze the possible protective role of Arctium lappa L. (AL) in a murine model of ulcerative colitis (UC). METHODS: BALB/c mice were administered 100 mg/kg AL powder orally each day. After 7 d, colitis was induced by administration of dextran sulfate sodium (DSS) (5% W/V) in drinking water for a further 8 consecutive days. Diarrhea and bloody stools as well as colonic histology were observed. The level of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in colonic sections were detected by immunohistochemistry. RESULTS: There were significant differences in mean body weight values and disease activity indices between controls and AL-treated animals. Moreover, the histological findings showed that AL treatment can prevent mucosal edema, submucosal erosions, ulceration, inflammatory cell infiltration and colon damage. In addition, immunohistochemistry analysis showed that the levels of the inflammatory cytokines, IL-6 and TNF-α were also decreased in AL-treated groups. CONCLUSION: We suggest that AL can prevent intestinal damage and decrease inflammatory cytokines in mice with DSS-induced colitis. Thus, AL could prove to be a useful food for UC. PMID:20806438

Watershed models for decision support in the Yakima River basin, Washington

USGS Publications Warehouse

Mastin, M.C.; Vaccaro, J.J.

2002-01-01

A Decision Support System (DSS) is being developed by the U.S. Geological Survey and the Bureau of Reclamation as part of a long-term project, the Watershed and River Systems Management Program. The goal of the program is to apply the DSS to U.S. Bureau of Reclamation projects in the western United States. The DSS was applied to the Reclamation's Yakima Project in the Yakima River Basin in eastern Washington. An important component of the DSS is the physical hydrology modeling. For the application to the Yakima River Basin, the physical hydrology component consisted of constructing four watershed models using the U.S. Geological Survey's Precipitation-Runoff Modeling System within the Modular Modeling System. The implementation of these models is described. To facilitate calibration of the models, mean annual streamflow also was estimated for ungaged subbasins. The models were calibrated for water years 1950-94 and tested for water years 1995-98. The integration of the models in the DSS for real-time water-management operations using an interface termed the Object User Interface is also described. The models were incorporated in the DSS for use in long-term to short-term planning and have been used in a real-time operational mode since water year 1999.

A Participants' DSS for a Management Game with a DSS Generator.

ERIC Educational Resources Information Center

Yeo, Gee Kin; Nah, Fui Hoon

1992-01-01

Describes the design of a decision support system (DSS) for a management game called MAGNUS (Management Game for National University of Singapore). Built-in models for performance analysis and decision making are explained; database query and model building are described; and future work is discussed. (11 references) (LRW)

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

PubMed

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

2017-07-01

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

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

PubMed

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

2015-09-22

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

Smad2/3 linker phosphorylation is a possible marker of cancer stem cells and correlates with carcinogenesis in a mouse model of colitis-associated colorectal cancer.

PubMed

Suzuki, Ryo; Fukui, Toshiro; Kishimoto, Masanobu; Miyamoto, Sachi; Takahashi, Yu; Takeo, Masahiro; Mitsuyama, Toshiyuki; Sakaguchi, Yutaku; Uchida, Kazushige; Nishio, Akiyoshi; Okazaki, Kazuichi

2015-07-01

Epithelial cells affected by somatic mutations undergo transition from a tumour-suppressive to a carcinogenic Smad pathway during sporadic colorectal carcinogenesis, and the specific linker threonine phosphorylation of Smad2/3 in colon epithelial cells indicates stem-like cells. This study extends previous observations to a model of colitis-associated colorectal cancer. After Crl:CD-1 mice received an administration of azoxymethane [AOM], the mice were given dextran sodium sulfate [DSS] for 7 days. AOM/DSS-treated mice [AOM/DSS mice] were killed at 10 or 20 weeks. After macroscopic observations, a histopathological analysis was conducted. Immunohistochemical staining was performed using the avidin-biotin immunoperoxidase method [pSmad3C-Ser, pSmad3L-Ser, c-Myc] and immunofluorescent methods [Ki67, β-catenin, CDK4, cyclin D1, Sox9, pSmad2/3L-Thr]. The colons from AOM/DSS mice were shorter than those from control mice. The number of colon tumours at Week 20 was higher than at Week 10. The inflammation scores for AOM/DSS mice were greater than those for control mice. Immunostaining-positive cells (staining by Ki67, β-catenin [nuclear and cytoplasmic], cyclin D1, and Sox9) were diffusely distributed in colon tumours. The percentage of pSmad3L-Ser-positive cells in colon tumours was higher than in sites of pre-neoplastic colitis, and that in sites of pre-neoplastic colitis was higher than in control mice. pSmad2/3L-Thr-positive cells were sparsely detected around crypt bases in non-neoplastic colon epithelia and at the tops of tumours, and immunohistochemical co-localisation of pSmad2/3L-Thr with Ki67 was not observed. Immunohistochemical co-localisation of pSmad2/3L-Thr with β-catenin and CDK4 was observed. pSmad3L-Ser signalling is an early event in colitis-associated colorectal cancer, and pSmad2/3L-Thr immunostaining-positive cells might be cancer stem cells. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Adenine Inhibits TNF-α Signaling in Intestinal Epithelial Cells and Reduces Mucosal Inflammation in a Dextran Sodium Sulfate-Induced Colitis Mouse Model.

PubMed

Fukuda, Toshihiko; Majumder, Kaustav; Zhang, Hua; Turner, Patricia V; Matsui, Toshiro; Mine, Yoshinori

2016-06-01

Adenine (6-amino-6H-purine), found in molokheiya (Corchorus olitorius L.), has exerted vasorelaxation effects in the thoracic aorta. However, the mode of action of the anti-inflammatory effect of adenine is unclear. Thus, we investigated to clarify the effect of adenine on chronic inflammation of the gastrointestinal tract. In intestinal epithelial cells, adenine significantly inhibited tumor necrosis factor-α-induced interleukin-8 secretion. The inhibition of adenine was abolished under the treatment of inhibitors of adenyl cyclase (AC) and protein kinase A (PKA), indicating the effect of adenine was mediated through the AC/PKA pathway. Adenine (5, 10, and 50 mg/kg BW/day) was administered orally for 14 days to female BALB/c mice, and then 5% dextran sodium sulfate (DSS) was given to induce colitis. Adenine (5 mg/kg BW/day) significantly prevented DSS-induced colon shortening, expression of pro-inflammatory cytokines, and histological damage in the colon. These results suggest that adenine can be a promising nutraceutical for the prevention of intestinal inflammation.

Oral administration of Lentinus edodes β-glucans ameliorates DSS-induced ulcerative colitis in mice via MAPK-Elk-1 and MAPK-PPARγ pathways.

PubMed

Shi, Limin; Lin, Qinlu; Yang, Tao; Nie, Ying; Li, Xinhua; Liu, Bo; Shen, Junjun; Liang, Ying; Tang, Yiping; Luo, Feijun

2016-11-09

To evaluate the anti-inflammatory effect of β-glucans from Lentinus edodes, and its molecular mechanism, the dextran sulfate sodium salt (DSS) induced colitis model of mice and the LPS-stimulated RAW264.7 cell inflammation model were used in this study. 40 ICR male mice were randomly divided into 4 groups: Control, DSS (DSS treated only), DSS + low-βGs (500 mg kg -1 d -1 ) and DSS + high-βGs (1000 mg kg -1 d -1 ). The body weight of the mice with Lentinus edodes β-glucan supplementation increased significantly compared to the DSS group and the disease activity index (DAI) was improved in both βG-treated groups. Compared with the DSS group, histopathological analysis showed that the infiltration of inflammatory cells of both βG-treated groups decreased significantly in colonic tissues. Furthermore, oral administration of β-glucans decreases the concentration of malondialdehyde (MDA) and myeloperoxidase (MPO) and inhibits the expression of iNOS and several inflammatory factors: TNF-α, IL-1β and IL-6 as well as nitric oxide (NO) of the colonic tissues. The mitogen-activated protein kinase (MAPK) pathway is closely related to the expression of pro-inflammatory factors. In the DSS-induced colitis model and the LPS-stimulated RAW264.7 cell model, βGs inhibited the expression of pro-inflammatory factors and blocked the phosphorylation of JNK/ERK1/2 and p38; βGs also suppress the phosphorylation of Elk-1 at Ser84 and the phosphorylation of PPARγ at Ser112. Altogether, these results suggest that Lentinus edodes βGs could inhibit the DSS-induced ulcerative colitis and decrease inflammatory factor expressions. The molecular mechanism may be involved in suppressing MAPK signaling and inactivation of Elk-1 and activation of PPARγ.

GridPV Toolbox

DOE Office of Scientific and Technical Information (OSTI.GOV)

Broderick, Robert; Quiroz, Jimmy; Grijalva, Santiago

2014-07-15

Matlab Toolbox for simulating the impact of solar energy on the distribution grid. The majority of the functions are useful for interfacing OpenDSS and MATLAB, and they are of generic use for commanding OpenDSS from MATLAB and retrieving GridPV Toolbox information from simulations. A set of functions is also included for modeling PV plant output and setting up the PV plant in the OpenDSS simulation. The toolbox contains functions for modeling the OpenDSS distribution feeder on satellite images with GPS coordinates. Finally, example simulations functions are included to show potential uses of the toolbox functions.

Decision support systems and the healthcare strategic planning process: a case study.

PubMed

Lundquist, D L; Norris, R M

1991-01-01

The repertoire of applications that comprises health-care decision support systems (DSS) includes analyses of clinical, financial, and operational activities. As a whole, these applications facilitate developing comprehensive and interrelated business and medical models that support the complex decisions required to successfully manage today's health-care organizations. Kennestone Regional Health Care System's use of DSS to facilitate strategic planning has precipitated marked changes in the organization's method of determining capital allocations. This case study discusses Kennestone's use of DSS in the strategic planning process, including profiles of key DSS modeling components.

Curcumin combined with turmerones, essential oil components of turmeric, abolishes inflammation-associated mouse colon carcinogenesis.

PubMed

Murakami, Akira; Furukawa, Ikuyo; Miyamoto, Shingo; Tanaka, Takuji; Ohigashi, Hajime

2013-01-01

Curcumin (CUR), a yellow pigment in turmeric, has marked potential for preventing colon cancer. We recently reported that ar-turmerone (ATM) suppressed nitric oxide (NO) generation in macrophages. In the present study, we explored the molecular mechanisms by which ATM attenuates NO generation and examined the anti-carcinogenesis activity of turmerones (TUR, a mixture of 5 sesquiterpenes including ATM). Both CUR and ATM inhibited lipopolysaccharide (LPS)-induced expression of inducible forms of both nitric oxide synthase and cyclooxygenase (iNOS and COX-2, respectively). A chase experiment using actinomycin D revealed that ATM accelerated the decay of iNOS and COX-2 mRNA, suggesting a post-transcriptional mechanism. ATM prevented LPS-induced translocation of HuR, an AU-rich element-binding protein that determines mRNA stability of certain inflammatory genes. In a colitis model, oral administration of TUR significantly suppressed 2% dextran sulfate sodium (DSS)-induced shortening of the large bowel by 52-58%. We also evaluated the chemopreventive effects of oral feeding of TUR, CUR, and their combinations using a model of dimethylhydradine-initiated and DSS-promoted mouse colon carcinogenesis. At the low dose, TUR markedly suppressed adenoma multiplicity by 73%, while CUR at both doses suppressed adenocarcinoma multiplicity by 63-69%. Interestingly, the combination of CUR and TUR at both low and high doses abolished tumor formation. Collectively, our results led to our hypothesis that TUR is a novel candidate for colon cancer prevention. Furthermore, we consider that its use in combination with CUR may become a powerful method for prevention of inflammation-associated colon carcinogenesis. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Hypertonic Saline Reduces Vascular Leakage in a Mouse Model of Severe Dengue

PubMed Central

Tan, Kar Wai; Angeli, Veronique; Moochhala, Shabbir; Ooi, Eng Eong; Alonso, Sylvie

2013-01-01

Dengue (DEN) is a mosquito-borne viral disease and represents a serious public health threat and an economical burden throughout the tropics. Dengue clinical manifestations range from mild acute febrile illness to severe DEN hemorrhagic fever/DEN shock syndrome (DHF/DSS). Currently, resuscitation with large volumes of isotonic fluid remains the gold standard of care for DEN patients who develop vascular leakage and shock. Here, we investigated the ability of small volume of hypertonic saline (HTS) suspensions to control vascular permeability in a mouse model of severe DEN associated with vascular leakage. Several HTS treatment regimens were considered and our results indicated that a single bolus of 7.5% NaCl at 4 mL per kg of body weight administered at the onset of detectable vascular leakage rapidly and significantly reduced vascular leak for several days after injection. This transient reduction of vascular leakage correlated with reduced intestine and liver damage with restoration of the hepatic functions, and resulted in delayed death of the infected animals. Mechanistically, we showed that HTS did not directly impact on the viral titers but resulted in lower immune cells counts and decreased systemic levels of soluble mediators involved in vascular permeability. In addition, we demonstrated that neutrophils do not play a critical role in DEN-associated vascular leakage and that the therapeutic effect of HTS is not mediated by its impact on the neutrophil counts. Together our data indicate that HTS treatment can transiently but rapidly reduce dengue-associated vascular leakage, and support the findings of a recent clinical trial which evaluated the efficacy of a hypertonic suspension to impact on vascular permeability in DSS children. PMID:23637867

Oral delivery of Lactococcus lactis that secretes bioactive heme oxygenase-1 alleviates development of acute colitis in mice.

PubMed

Shigemori, Suguru; Watanabe, Takafumi; Kudoh, Kai; Ihara, Masaki; Nigar, Shireen; Yamamoto, Yoshinari; Suda, Yoshihito; Sato, Takashi; Kitazawa, Haruki; Shimosato, Takeshi

2015-11-25

Mucosal delivery of therapeutic proteins using genetically modified strains of lactic acid bacteria (gmLAB) is being investigated as a new therapeutic strategy. We developed a strain of gmLAB, Lactococcus lactis NZ9000 (NZ-HO), which secretes the anti-inflammatory molecule recombinant mouse heme oxygenase-1 (rmHO-1). The effects of short-term continuous oral dosing with NZ-HO were evaluated in mice with dextran sulfate sodium (DSS)-induced acute colitis as a model of inflammatory bowel diseases (IBD). We identified the secretion of rmHO-1 by NZ-HO. rmHO-1 was biologically active as determined with spectroscopy. Viable NZ-HO was directly delivered to the colon via oral administration, and rmHO-1 was secreted onto the colonic mucosa in mice. Acute colitis in mice was induced by free drinking of 3 % DSS in water and was accompanied by an increase in the disease activity index score and histopathological changes. Daily oral administration of NZ-HO significantly improved these colitis-associated symptoms. In addition, NZ-HO significantly increased production of the anti-inflammatory cytokine interleukin (IL)-10 and decreased the expression of pro-inflammatory cytokines such as IL-1α and IL-6 in the colon compared to a vector control strain. Oral administration of NZ-HO alleviates DSS-induced acute colitis in mice. Our results suggest that NZ-HO may be a useful mucosal therapeutic agent for treating IBD.

Sustained neurochemical plasticity in central terminals of mouse DRG neurons following colitis.

PubMed

Benson, Jessica R; Xu, Jiameng; Moynes, Derek M; Lapointe, Tamia K; Altier, Christophe; Vanner, Stephen J; Lomax, Alan E

2014-05-01

Sensitization of dorsal root ganglia (DRG) neurons is an important mechanism underlying the expression of chronic abdominal pain caused by intestinal inflammation. Most studies have focused on changes in the peripheral terminals of DRG neurons in the inflamed intestine but recent evidence suggests that the sprouting of central nerve terminals in the dorsal horn is also important. Therefore, we examine the time course and reversibility of changes in the distribution of immunoreactivity for substance P (SP), a marker of the central terminals of DRG neurons, in the spinal cord during and following dextran sulphate sodium (DSS)-induced colitis in mice. Acute and chronic treatment with DSS significantly increased SP immunoreactivity in thoracic and lumbosacral spinal cord segments. This increase developed over several weeks and was evident in both the superficial laminae of the dorsal horn and in lamina X. These increases persisted for 5 weeks following cessation of both the acute and chronic models. The increase in SP immunoreactivity was not observed in segments of the cervical spinal cord, which were not innervated by the axons of colonic afferent neurons. DRG neurons dissociated following acute DSS-colitis exhibited increased neurite sprouting compared with neurons dissociated from control mice. These data suggest significant colitis-induced enhancements in neuropeptide expression in DRG neuron central terminals. Such neurotransmitter plasticity persists beyond the period of active inflammation and might contribute to a sustained increase in nociceptive signaling following the resolution of inflammation.

Vanillin-Ameliorated Development of Azoxymethane/Dextran Sodium Sulfate-Induced Murine Colorectal Cancer: The Involvement of Proteasome/Nuclear Factor-κB/Mitogen-Activated Protein Kinase Pathways.

PubMed

Li, Jung-Miao; Lee, Yu-Chen; Li, Chia-Cheng; Lo, Hsin-Yi; Chen, Feng-Yuan; Chen, Yi-Siou; Hsiang, Chien-Yun; Ho, Tin-Yun

2018-06-06

Vanillin is a natural dietary flavoring widely used in the food industry. Colorectal cancer (CRC) is one of the common malignancies in the world. Chronic intestinal inflammation is a risk factor for the development of CRC. We have previously found that vanillin improves and prevents colitis in mice. Here we evaluated the inhibitory activities of vanillin on a mouse model of colitis-induced CRC. Mice were challenged intraperitoneally with azoxymethane (AOM) and orally with dextran sodium sulfate (DSS). Various dosages of vanillin were orally administered for 13 consecutive weeks. Vanillin alleviated the development of tumors in AOM/DSS-induced mice. The total number of tumors in 100 mg/kg vanillin group was significantly reduced by 57.14 ± 7.67%, compared with sham group. Gene expression analysis showed that vanillin downregulated the expression levels of proteasome genes in colon tissues. Moreover, vanillin at 10 mM significantly suppressed proteasome activities in HCT-116 cells by 41.27 ± 0.41%. Furthermore, vanillin diminished the phosphorylation of mitogen-activated protein kinases (MAPKs) and reduced the number of p65-positive cells, proliferating cells, and granulocytes in colon tissues with statistical significance. In conclusion, our data suggested that vanillin was a bioactive compound that ameliorated the development of AOM/DSS-induced colon cancer in mice. Moreover, the amelioration of vanillin might be associated with the downregulation of proteasome, nuclear factor-κB, and MAPK pathways.

Activating PXR by Imperatorin Attenuates Dextran Sulphate Sodium-Induced Colitis in Mice.

PubMed

Liu, Meijing; Zhang, Guohui; Zheng, Chunge; Song, Meng; Liu, Fangle; Huang, Xiaotao; Bai, Shasha; Huang, Xinan; Lin, Chaozhan; Zhu, Chenchen; Hu, Yingjie; Mi, Suiqing; Liu, Changhui

2018-06-26

The activation of human pregnane X receptor (PXR) has potential therapeutic uses for inflammatory bowel disease (IBD). Imperatorin (IMP), a naturally-occurring coumarin, is the main bioactive ingredient of Angelica dahurica Radix, which is regularly used to treat the common cold and intestinal disorders. However, there are no data on the protective effects of IMP against IBD. The effects of IMP on PXR-modulated cytochrome P450 3A4 (CYP3A4) expression were assessed using a PXR transactivation assay, a mammalian two-hybrid assay, a competitive ligand-binding assay, analysis of CYP3A4 mRNA and protein expression levels, and measurement of CYP3A4 activity using a cell-based reporter gene assay and in vitro model. The inhibitory effects of IMP on NF-κB activity was evaluated by a reporter assay and NF-κB p65 nuclear translocation. The anti-IBD effects of IMP were investigated in a dextran sulphate sodium (DSS)-induced colitis mouse model. Colon inflammatory cytokines were assessed by ELISA. IMP activated CYP3A4 promoter activity, recruited steroid receptor coactivator 1 (SRC-1) to the ligand-binding domain of PXR, and increased the expression and activity of CYP3A4. However, PXR knockdown substantially reduced PXR-mediated CYP3A4 expression. Furthermore, IMP-mediated PXR activation suppressed NF-κB nuclear translocation and downregulated lipopolysaccharide-induced proinflammatory gene expression. Nevertheless, PXR knockdown partially reduced the IMP-mediated inhibition of NF-κB. IMP ameliorated DSS-induced colitis by PXR/NF-κB signalling. IMP serves as a PXR agonist to attenuate DSS-induced colitis by the suppression of the NF-κB-mediated proinflammatory response in a PXR/NF-κB- dependent manner. This article is protected by copyright. All rights reserved.

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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Aping; Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan; Yang, Hang

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

Modeling and analysis of the DSS-14 antenna control system

NASA Technical Reports Server (NTRS)

Gawronski, W.; Bartos, R.

1996-01-01

An improvement of pointing precision of the DSS-14 antenna is planned for the near future. In order to analyze the improvement limits and to design new controllers, a precise model of the antenna and the servo is developed, including a finite element model of the antenna structure and detailed models of the hydraulic drives and electronic parts. The DSS-14 antenna control system has two modes of operation: computer mode and precision mode. The principal goal of this investigation is to develop the model of the computer mode and to evaluate its performance. The DSS-14 antenna computer model consists of the antenna structure and drives in azimuth and elevation. For this model, the position servo loop is derived, and simulations of the closed-loop antenna dynamics are presented. The model is significantly different from that for the 34-m beam-waveguide antennas.

Berberine Regulates Treg/Th17 Balance to Treat Ulcerative Colitis Through Modulating the Gut Microbiota in the Colon.

PubMed

Cui, Huantian; Cai, Yuzi; Wang, Li; Jia, Beitian; Li, Junchen; Zhao, Shuwu; Chu, Xiaoqian; Lin, Jin; Zhang, Xiaoyu; Bian, Yuhong; Zhuang, Pengwei

2018-01-01

Berberine (BBR), an alkaloid isolated from Rhizoma Coptidis, Cortex Phellode , and Berberis , has been widely used in the treatment of ulcerative colitis (UC). However, the mechanism of BBR on UC is unknown. In this study, we investigated the activities of T regulatory cell (Treg) and T helper 17 cell (Th17) in a dextran sulfate sodium (DSS)-induced UC mouse model after BBR administration. We also investigated the changes of gut microbiota composition using 16S rRNA analysis. We also examined whether BBR could regulate the Treg/Th17 balance by modifying gut microbiota. The mechanism was further confirmed by depleting gut microbiota through a combination of antibiotic treatment and fecal transplantations. Results showed that BBR treatment could improve the Treg/Th17 balance in the DSS-induced UC model. BBR also reduced diversity of the gut microbiota and interfered with the relative abundance of Desulfovibrio, Eubacterium , and Bacteroides. Moreover, BBR treatment did not influence the Treg/Th17 balance after the depletion of gut microbiota. Our results also revealed that fecal transplantation from BBR-treated mice could relieve UC and regulate the Treg/Th17 balance. In conclusion, our study provides evidence that BBR prevents UC by modifying gut microbiota and regulating the balance of Treg/Th17.

Human cord blood-derived platelet lysate enhances the therapeutic activity of adipose-derived mesenchymal stromal cells isolated from Crohn's disease patients in a mouse model of colitis.

PubMed

Forte, Dorian; Ciciarello, Marilena; Valerii, Maria Chiara; De Fazio, Luigia; Cavazza, Elena; Giordano, Rosaria; Parazzi, Valentina; Lazzari, Lorenza; Laureti, Silvio; Rizzello, Fernando; Cavo, Michele; Curti, Antonio; Lemoli, Roberto M; Spisni, Enzo; Catani, Lucia

2015-09-09

Due to their immunomodulatory properties, mesenchymal stromal cells (MSCs) have been used for auto-immune disease treatment. Crohn disease (CD) and ulcerative colitis are two major inflammatory bowel diseases (IBDs), resulting from pathological immune responses to environmental or microbial antigens. Preclinical and clinical studies have suggested that MSC-based cellular therapy hold promising potential for IBD treatment. However, open issues include the selection of the proper cell dose, the source and the optimal route of administration of MSCs for more effective results. Platelet lysate has gained clinical interest due to its efficacy in accelerating wound healing. Thus, we propose to combine the administration of MSCs with a human umbilical cord blood-derived platelet lysate (hCBPL) as a novel strategy to improve MSC-based therapy for IBD resolution. Colitis was induced in 8-week-old C57BL/6J mice by daily oral administration of dextran sulphate sodium (DSS) (1.5 % w/v in tap water) for 9 days. MSCs were isolated from adipose tissue of CD patients (adCD-MSCs), expanded in proliferation medium, resuspended in hCBPL or PBS and administrated via enema for three times (1 × 10(6) cells/mouse/time) every other day starting on day +7 from DSS induction. The colitis evolution was evaluated by daily monitoring of body weight, stool consistency and bleeding. Histopathological analysis was performed. Inflammatory cytokine plasma levels were determined. adCD-MSCs stained with lipophilic membrane dye Nile Red, were injected in DSS mice as described above. Colon section of mice sacrificed 24 hours after last cell administration, were analyzed by confocal microscopy. We found that adCD-MSCs could be easily isolated and expanded from CD patients. Upon injection, adCD-MSCs exerted a therapeutic effect on DSS-induced colitis. Moreover, hCBPL increased adCD-MSCs efficacy by significantly reducing colitis scores, extension of the colon inflamed area and plasma levels of inflammatory mediators. Finally, Nile Red staining of MSCs is very efficient, stable and does not impair their vitality and function. Nile Red-labelling was clearly detected in the colitic area of adCD-MSCs injected mice and it was significantly brighter in the colon sections of mice that had received adCD-MSCs/hCBPL. In summary, with this study we propose a novel and promising adCD-MSC/hCBPL-based therapy for refractory IBDs.

On DSS Implementation in the Dynamic Model of the Digital Oil field

NASA Astrophysics Data System (ADS)

Korovin, Iakov S.; Khisamutdinov, Maksim V.; Kalyaev, Anatoly I.

2018-02-01

Decision support systems (DSS), especially based on the artificial intelligence (AI) techniques are been widely applied in different domains nowadays. In the paper we depict an approach of implementing DSS in to Digital Oil Field (DOF) dynamic model structure in order to reduce the human factor influence, considering the automation of all production processes to be the DOF model clue element. As the basic tool of data handling we propose the hybrid application on artificial neural networks and evolutional algorithms.

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

PubMed Central

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

2016-01-01

AIM To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid (CB) receptors, WIN55-212-2 (WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future. METHODS We established the colitis model in C57BL/6 mice by replacing the animals’ water supply with 4% dextran sulfate sodium (DSS) for 7 consecutive days. A colitis scoring system was used to evaluate the severity of colon local lesion. The plasma levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the myeloperoxidase (MPO) activity in colon tissue were measured. The expressions of cannabinoid receptors, claudin-1 protein, p38 mitogen-activated protein kinase (p38MAPK) and its phosphorylated form (p-p38) in colon tissue were determined by immunohistochemistry and Western blot. In addition, the effect of SB203580 (SB), an inhibitor of p38, was investigated in parallel experiments, and the data were compared with those from intervention groups of WIN55 and SB alone or used together. RESULTS The results demonstrated that WIN55 or SB treatment alone or together improved the pathological changes in mice with DSS colitis, decreased the plasma levels of TNF-α, and IL-6, and MPO activity in colon. The enhanced expression of claudin-1 and the inhibited expression of p-p38 in colon tissues were found in the WIN55-treated group. Besides, the expression of CB1 and CB2 receptors was enhanced in the colon after the induction of DSS colitis, but reduced when p38MAPK was inhibited. CONCLUSION These results confirmed the anti-inflammatory effect and protective role of WIN55 on the mice with experimental colitis, and revealed that this agent exercises its action at least partially by inhibiting p38MAPK. Furthermore, the results showed that SB203580, affected the expression of CB1 and CB2 receptors in the mouse colon, suggesting a close linkage and cross-talk between the p38MAPK signaling pathway and the endogenous CB system. PMID:27920472

Automating hypertext for decision support

NASA Technical Reports Server (NTRS)

Bieber, Michael

1990-01-01

A decision support system (DSS) shell is being constructed that can support applications in a variety of fields, e.g., engineering, manufacturing, finance. The shell provides a hypertext-style interface for 'navigating' among DSS application models, data, and reports. The traditional notion of hypertext had to be enhanced. Hypertext normally requires manually, pre-defined links. A DSS shell, however, requires that hypertext connections to be built 'on the fly'. The role of hypertext is discussed in augmenting DSS applications and the decision making process. Also discussed is how hypertext nodes, links, and link markers tailored to an arbitrary DSS application were automatically generated.

In vivo treatment with the herbal phenylethanoid acteoside ameliorates intestinal inflammation in dextran sulphate sodium-induced colitis

PubMed Central

Hausmann, M; Obermeier, F; Paper, D H; Balan, K; Dunger, N; Menzel, K; Falk, W; Schoelmerich, J; Herfarth, H; Rogler, G

2007-01-01

Recently we demonstrated that in inflammatory bowel disease (IBD) macrophage-oxidative burst activity is increased and NADPH oxidase mRNA is induced. The herbal phenylethanoid acteoside isolated from Plantago lanceolata L. was shown to exhibit anti-oxidative potential. Using the dextran sulphate sodium (DSS)-induced colitis model, in this study we have assessed whether systemic application of acteoside affects colitis. Colitis was induced by DSS in Balb/c mice. Treatment with acteoside (120, 600 µg/mouse/day) was performed intraperitoneally. The colon lengths were determined. Colonic tissue was scored histologically (max. score 8) by a blinded investigator. T cells isolated from mesenteric lymph nodes (MLN) were stimulated with anti-CD3 antibody in the presence of interleukin (IL)-2 (final concentration 10 U/ml). After incubation for 24 h, IL-1β, IL-6, IL-12 tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels in supernatants were analysed by the beadlyte® cytokine detection system. Histological scoring of colonic tissue revealed that application of acteoside was followed by a significantly improved histological score. In acute colitis the histological score was 3·2 with acteoside versus 5·2 with phosphate-buffered saline (PBS) (P < 0·02). In chronic colitis both 120 µg (3·3 versus 5·2) or 600 µg acteoside (3·0 versus 5·2) significantly ameliorated colitis (both P < 0·02). Stimulated MLN from mice with chronic DSS-induced colitis treated with acteoside showed a significant down-regulation of IFN-γ secretion (195 pg/ml with 600 µg acteoside versus 612 pg/ml with PBS, P < 0·02). Inhibition of oxidative burst activity with acteoside reduced mucosal tissue damage in DSS colitis and could be a therapeutic alternative for IBD treatment. Further studies of this agent are warranted. PMID:17437425

LandCaRe DSS--an interactive decision support system for climate change impact assessment and the analysis of potential agricultural land use adaptation strategies.

PubMed

Wenkel, Karl-Otto; Berg, Michael; Mirschel, Wilfried; Wieland, Ralf; Nendel, Claas; Köstner, Barbara

2013-09-01

Decision support to develop viable climate change adaptation strategies for agriculture and regional land use management encompasses a wide range of options and issues. Up to now, only a few suitable tools and methods have existed for farmers and regional stakeholders that support the process of decision-making in this field. The interactive model-based spatial information and decision support system LandCaRe DSS attempts to close the existing methodical gap. This system supports interactive spatial scenario simulations, multi-ensemble and multi-model simulations at the regional scale, as well as the complex impact assessment of potential land use adaptation strategies at the local scale. The system is connected to a local geo-database and via the internet to a climate data server. LandCaRe DSS uses a multitude of scale-specific ecological impact models, which are linked in various ways. At the local scale (farm scale), biophysical models are directly coupled with a farm economy calculator. New or alternative simulation models can easily be added, thanks to the innovative architecture and design of the DSS. Scenario simulations can be conducted with a reasonable amount of effort. The interactive LandCaRe DSS prototype also offers a variety of data analysis and visualisation tools, a help system for users and a farmer information system for climate adaptation in agriculture. This paper presents the theoretical background, the conceptual framework, and the structure and methodology behind LandCaRe DSS. Scenario studies at the regional and local scale for the two Eastern German regions of Uckermark (dry lowlands, 2600 km(2)) and Weißeritz (humid mountain area, 400 km(2)) were conducted in close cooperation with stakeholders to test the functionality of the DSS prototype. The system is gradually being transformed into a web version (http://www.landcare-dss.de) to ensure the broadest possible distribution of LandCaRe DSS to the public. The system will be continuously developed, updated and used in different research projects and as a learning and knowledge-sharing tool for students. The main objective of LandCaRe DSS is to provide information on the complex long-term impacts of climate change and on potential management options for adaptation by answering "what-if" type questions. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xin; Mandal, Ardhendu K.; Saito, Hiroshi

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 revealedmore » 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.« less

Grid Integrated Distributed PV (GridPV) Version 2.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reno, Matthew J.; Coogan, Kyle

2014-12-01

This manual provides the documentation of the MATLAB toolbox of functions for using OpenDSS to simulate the impact of solar energy on the distribution system. The majority of the functio ns are useful for interfacing OpenDSS and MATLAB, and they are of generic use for commanding OpenDSS from MATLAB and retrieving information from simulations. A set of functions is also included for modeling PV plant output and setting up the PV plant in th e OpenDSS simulation. The toolbox contains functions for modeling the OpenDSS distribution feeder on satellite images with GPS coordinates. Finally, example simulations functions are included tomore » show potential uses of the toolbox functions. Each function i n the toolbox is documented with the function use syntax, full description, function input list, function output list, example use, and example output.« less

Supplementation of Low- and High-fat Diets with Fermentable Fiber Exacerbates Severity of DSS-induced Acute Colitis.

PubMed

Miles, Jennifer P; Zou, Jun; Kumar, Matam-Vijay; Pellizzon, Michael; Ulman, Edward; Ricci, Matthew; Gewirtz, Andrew T; Chassaing, Benoit

2017-07-01

Lack of dietary fiber has been suggested to increase the risk of developing various chronic inflammatory diseases, whereas supplementation of diets with fiber might offer an array of health-promoting benefits. Consistent with this theme, we recently reported that in mice, compositionally defined diets that are made with purified ingredients and lack fermentable fiber promote low-grade inflammation and metabolic syndrome, both of which could be ameliorated by supplementation of such diets with the fermentable fiber inulin. Herein, we examined if, relative to a grain-based mouse diet (chow), compositionally defined diet consumption would impact development of intestinal inflammation induced by dextran sulfate sodium (DSS) and moreover, whether DSS-induced colitis might also be attenuated by diets supplemented with inulin. Analogous to their promotion of low-grade inflammation, compositionally defined diet of high- and low-fat content with cellulose increased the severity of DSS-induced colitis relative to chow. However, in contrast to the case of low-grade inflammation, addition of inulin, but not the insoluble fiber cellulose, further exacerbated the severity of colitis and its associated clinical manifestations (weight loss and bleeding) in both low- and high-fat diets. While inulin, and perhaps other fermentable fibers, can ameliorate low-grade inflammation and associated metabolic disease, it also has the potential to exacerbate disease severity in response to inducers of acute colitis.

Purified rutin and rutin-rich asparagus attenuates disease severity and tissue damage following dextran sodium sulfate-induced colitis.

PubMed

Power, Krista A; Lu, Jenifer T; Monk, Jennifer M; Lepp, Dion; Wu, Wenqing; Zhang, Claire; Liu, Ronghua; Tsao, Rong; Robinson, Lindsay E; Wood, Geoffrey A; Wolyn, David J

2016-11-01

This study investigated the effects of cooked whole asparagus (ASP) versus its equivalent level of purified flavonoid glycoside, rutin (RUT), on dextran sodium sulfate (DSS)-induced colitis and subsequent colitis recovery in mice. C57BL/6 male mice were fed an AIN-93G basal diet (BD), or BD supplemented with 2% cooked ASP or 0.025% RUT for 2 wks prior to and during colitis induction with 2% DSS in water for 7 days, followed by 5 days colitis recovery. In colitic mice, both ASP and RUT upregulated mediators of improved barrier integrity and enhanced mucosal injury repair (e.g. Muc1, IL-22, Rho-A, Rac1, and Reg3γ), increased the proportion of mouse survival, and improved disease activity index. RUT had the greatest effect in attenuating DSS-induced colonic damage indicated by increased crypt and goblet cell restitution, reduced colonic myeloperoxidase, as well as attenuated DSS-induced microbial dysbiosis (reduced Enterobacteriaceae and Bacteroides, and increased unassigned Clostridales, Oscillospira, Lactobacillus, and Bifidobacterium). These findings demonstrate that dietary cooked ASP and its flavonoid glycoside, RUT, may be useful in attenuating colitis severity by modulating the colonic microenvironment resulting in reduced colonic inflammation, promotion of colonic mucosal injury repair, and attenuation of colitis-associated microbial dysbiosis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Upregulation of P-glycoprotein by probiotics in intestinal epithelial cells and in the dextran sulfate sodium model of colitis in mice

PubMed Central

Goyal, Sonia; Raheja, Geetu; Singh, Varsha; Akhtar, Maria; Nazir, Talat M.; Alrefai, Waddah A.; Gill, Ravinder K.; Dudeja, Pradeep K.

2011-01-01

P-glycoprotein (P-gp) mediates efflux of xenobiotics and bacterial toxins from the intestinal mucosa into the lumen. Dysregulation of P-gp has been implicated in inflammatory bowel disease. Certain probiotics have been shown to be effective in treating inflammatory bowel disease. However, direct effects of probiotics on P-gp are not known. Current studies examined the effects of Lactobacilli on P-gp function and expression in intestinal epithelial cells. Caco-2 monolayers and a mouse model of dextran sulfate sodium-induced colitis were utilized. P-gp activity was measured as verapamil-sensitive [3H]digoxin transepithelial flux. Multidrug resistant 1 (MDR1)/P-gp expression was measured by real-time quantitative PCR and immunoblotting. Culture supernatant (CS; 1:10 or 1:50, 24 h) of Lactobacillus acidophilus or Lactobacillus rhamnosus treatment of differentiated Caco-2 monolayers (21 days postplating) increased (∼3-fold) MDR1/P-gp mRNA and protein levels. L. acidophilus or L. rhamnosus CS stimulated P-gp activity (∼2-fold, P < 0.05) via phosphoinositide 3-kinase and ERK1/2 MAPK pathways. In mice, L. acidophilus or L. rhamnosus treatment (3 × 109 colony-forming units) increased mdr1a/P-gp mRNA and protein expression in the ileum and colon (2- to 3-fold). In the dextran sulfate sodium (DSS)-induced colitis model (3% DSS in drinking water for 7 days), the degree of colitis as judged by histological damage and myeloperoxidase activity was reduced by L. acidophilus. L. acidophilus treatment to DSS-treated mice blocked the reduced expression of mdr1a/P-gp mRNA and protein in the distal colon. These findings suggest that Lactobacilli or their soluble factors stimulate P-gp expression and function under normal and inflammatory conditions. These data provide insights into a novel mechanism involving P-gp upregulation in beneficial effects of probiotics in intestinal inflammatory disorders. PMID:21350189

Matlab-Excel Interface for OpenDSS

DOE Office of Scientific and Technical Information (OSTI.GOV)

The software allows users of the OpenDSS grid modeling software to access their load flow models using a GUI interface developed in MATLAB. The circuit definitions are entered into a Microsoft Excel spreadsheet which makes circuit creation and editing a much simpler process than the basic text-based editors used in the native OpenDSS interface. Plot tools have been developed which can be accessed through a MATLAB GUI once the desired parameters have been simulated.

Therapeutic effect of the natural compounds baicalein and baicalin on autoimmune diseases.

PubMed

Xu, Jian; Liu, Jinlong; Yue, Guolin; Sun, Mingqiang; Li, Jinliang; Xiu, Xia; Gao, Zhenzhong

2018-05-23

A series of natural compounds have been implicated to be useful in regulating the pathogenesis of various autoimmune diseases. The present study demonstrated that the Scutellariae radix compounds baicalein and baicalin may serve as drugs for the treatment of autoimmune diseases, including rheumatoid arthritis and inflammatory bowel disease. Following the administration of baicalein and baicalin in vivo, T cell‑mediated autoimmune diseases in the mouse model were profoundly ameliorated: In the collagen‑induced arthritis model (CIA), the severity of the disease was reduced by baicalein and, consistently, baicalein was demonstrated to suppress T cell proliferation in CIA mice. In the dextran sodium sulfate (DSS)‑induced colitis model, the disease was attenuated by baicalin, and baicalin promoted colon epithelial cell (CEC) proliferation in vitro. The present study further revealed that the mRNA expression of signal transducer and activator of transcription (STAT)3 and STAT4 in the tyrosine‑protein kinase JAK‑STAT signaling pathway in T cells was downregulated by baicalein, contributing to its regulation of T cell proliferation. However, in the DSS model, the STAT4 transcription in CECs, which are the target cells of activated T cells in the gut, was downregulated by baicalin, suggesting that baicalein and baicalin mediated similar STAT expression in different cell types in autoimmune diseases. In conclusion, the similarly structured compounds baicalein and baicalin selectively exhibited therapeutic effects on autoimmune diseases by regulating cell proliferation and STAT gene expression, albeit in different cell types.

NoxO1 Controls Proliferation of Colon Epithelial Cells.

PubMed

Moll, Franziska; Walter, Maria; Rezende, Flávia; Helfinger, Valeska; Vasconez, Estefania; De Oliveira, Tiago; Greten, Florian R; Olesch, Catherine; Weigert, Andreas; Radeke, Heinfried H; Schröder, Katrin

2018-01-01

Reactive oxygen species (ROS) produced by enzymes of the NADPH oxidase family serve as second messengers for cellular signaling. Processes such as differentiation and proliferation are regulated by NADPH oxidases. In the intestine, due to the exceedingly fast and constant renewal of the epithelium both processes have to be highly controlled and balanced. Nox1 is the major NADPH oxidase expressed in the gut, and its function is regulated by cytosolic subunits such as NoxO1. We hypothesize that the NoxO1-controlled activity of Nox1 contributes to a proper epithelial homeostasis and renewal in the gut. NoxO1 is highly expressed in the colon. Knockout of NoxO1 reduces the production of superoxide in colon crypts and is not subsidized by an elevated expression of its homolog p47phox. Knockout of NoxO1 increases the proliferative capacity and prevents apoptosis of colon epithelial cells. In mouse models of dextran sulfate sodium (DSS)-induced colitis and azoxymethane/DSS induced colon cancer, NoxO1 has a protective role and may influence the population of natural killer cells. NoxO1 affects colon epithelium homeostasis and prevents inflammation.

Dietary Nanosized Lactobacillus plantarum Enhances the Anticancer Effect of Kimchi on Azoxymethane and Dextran Sulfate Sodium-Induced Colon Cancer in C57BL/6J Mice.

PubMed

Lee, Hyun Ah; Kim, Hyunung; Lee, Kwang-Won; Park, Kun-Young

2016-01-01

This study was undertaken to evaluate enhancement of the chemopreventive properties of kimchi by dietary nanosized Lactobacillus (Lab.)plantarum (nLp) in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated colorectal cancer C57BL/6J mouse model. nLp is a dead, shrunken, processed form of Lab. Plantarum isolated from kimchi that is 0.5-1.0 µm in size. The results obtained showed that animals fed kimchi with nLp (K-nLp) had longer colons and lower colon weights/length ratios and developed fewer tumors than mice fed kimchi alone (K). In addition, K-nLp administration reduced levels of proinflammatory cytokine serum levels and mediated the mRNA and protein expressions of inflammatory, apoptotic, and cell-cycle markers to suppress inflammation and induce tumor-cell apoptosis and cell-cycle arrest. Moreover, it elevated natural killer-cell cytotoxicity. The study suggests adding nLp to kimchi could improve the suppressive effect of kimchi on AOM/DSS-induced colorectal cancer. These findings indicate nLp has potential use as a functional chemopreventive ingredient in the food industry.

Changes in protein expression after treatment with Ancylostoma caninum excretory/secretory products in a mouse model of colitis

PubMed Central

Sotillo, Javier; Ferreira, Ivana; Potriquet, Jeremy; Laha, Thewarach; Navarro, Severine; Loukas, Alex; Mulvenna, Jason

2017-01-01

Different reports have highlighted the potential use of helminths and their secretions in the treatment of inflammatory bowel disease (IBD) conditions; however, no reports have investigated their effects at a proteome level. Herein, we characterise the protein expression changes that occur in lamina propria (LP) and the intestinal epithelial cells (IEC) of mice with dextran sulfate sodium (DSS)-induced colitis treated with Ancylostoma caninum excretory/secretory (ES) products using a quantitative proteomic approach. We have shown how parasite products can significantly alter the expression of proteins involved in immune responses, cell death and with an antioxidant activity. Interestingly, significant changes in the expression levels of different mucins were observed in this study. MUC13, a mucin implicated in gastrointestinal homeostasis, was upregulated in the LP of mice with DSS-induced colitis treated with ES, while MUC2, a major component of mucus, was upregulated in the IEC. In addition, A. caninum proteins have an important effect on proteins with antioxidant functions and proteins involved in intestinal homeostasis and tissue integrity and regeneration. Understanding how parasites can ameliorate IBD pathogenesis can help us design novel treatments for autoimmune diseases. PMID:28191818

Acute murine colitis reduces colonic 5-aminosalicylic acid metabolism by regulation of N-acetyltransferase-2

PubMed Central

Ramírez-Alcántara, Verónica

2014-01-01

Pharmacotherapy based on 5-aminosalicylic acid (5-ASA) is a preferred treatment for ulcerative colitis, but variable patient response to this therapy is observed. Inflammation can affect therapeutic outcomes by regulating the expression and activity of drug-metabolizing enzymes; its effect on 5-ASA metabolism by the colonic arylamine N-acetyltransferase (NAT) enzyme isoforms is not firmly established. We examined if inflammation affects the capacity for colonic 5-ASA metabolism and NAT enzyme expression. 5-ASA metabolism by colonic mucosal homogenates was directly measured with a novel fluorimetric rate assay. 5-ASA metabolism reported by the assay was dependent on Ac-CoA, inhibited by alternative NAT substrates (isoniazid, p-aminobenzoylglutamate), and saturable with Km (5-ASA) = 5.8 μM. A mouse model of acute dextran sulfate sodium (DSS) colitis caused pronounced inflammation in central and distal colon, and modest inflammation of proximal colon, defined by myeloperoxidase activity and histology. DSS colitis reduced capacity for 5-ASA metabolism in central and distal colon segments by 52 and 51%, respectively. Use of selective substrates of NAT isoforms to inhibit 5-ASA metabolism suggested that mNAT2 mediated 5-ASA metabolism in normal and colitis conditions. Western blot and real-time RT-PCR identified that proximal and distal mucosa had a decreased mNAT2 protein-to-mRNA ratio after DSS. In conclusion, an acute colonic inflammation impairs the expression and function of mNAT2 enzyme, thereby diminishing the capacity for 5-ASA metabolism by colonic mucosa. PMID:24742986

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

Calcium-mediated oxidative stress: a common mechanism in tight junction disruption by different types of cellular stress.

PubMed

Gangwar, Ruchika; Meena, Avtar S; Shukla, Pradeep K; Nagaraja, Archana S; Dorniak, Piotr L; Pallikuth, Sandeep; Waters, Christopher M; Sood, Anil; Rao, RadhaKrishna

2017-02-20

The role of reactive oxygen species (ROS) in osmotic stress, dextran sulfate sodium (DSS) and cyclic stretch-induced tight junction (TJ) disruption was investigated in Caco-2 cell monolayers in vitro and restraint stress-induced barrier dysfunction in mouse colon in vivo Live cell imaging showed that osmotic stress, cyclic stretch and DSS triggered rapid production of ROS in Caco-2 cell monolayers, which was blocked by depletion of intracellular Ca 2+ by 1,2-bis-( o -aminophenoxy)ethane- N , N , N ', N '-tetraacetic acid. Knockdown of Ca V 1.3 or TRPV6 channels blocked osmotic stress and DSS-induced ROS production and attenuated TJ disruption and barrier dysfunction. N -Acetyl l-cysteine (NAC) and l- N G -Nitroarginine methyl ester (l-NAME) blocked stress-induced TJ disruption and barrier dysfunction. NAC and l-NAME also blocked stress-induced activation of c-Jun N -terminal kinase (JNK) and c-Src. ROS was colocalized with the mitochondrial marker in stressed cells. Cyclosporin A blocked osmotic stress and DSS-induced ROS production, barrier dysfunction, TJ disruption and JNK activation. Mitochondria-targeted Mito-TEMPO blocked osmotic stress and DSS-induced barrier dysfunction and TJ disruption. Chronic restraint stress in mice resulted in the elevation of intracellular Ca 2+ , activation of JNK and c-Src, and disruption of TJ in the colonic epithelium. Furthermore, corticosterone administration induced JNK and c-Src activation, TJ disruption and protein thiol oxidation in colonic mucosa. The present study demonstrates that oxidative stress is a common signal in the mechanism of TJ disruption in the intestinal epithelium by different types of cellular stress in vitro and bio behavioral stress in vivo . © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Calcium-Mediated Oxidative Stress: a Common Mechanism in Tight Junction Disruption by Different Types of Cellular Stress

PubMed Central

Gangwar, Ruchika; Meena, Avtar S.; Shukla, Pradeep K.; Nagaraja, Archana S.; Dorniak, Piotr L.; Pallikuth, Sandeep; Waters, Christopher M.; Sood, Anil; Rao, RadhaKrishna

2017-01-01

The role of reactive oxygen species (ROS) in osmotic stress, dextran sulfate sodium (DSS) and cyclic stretch-induced tight junction disruption was investigated in Caco-2 cell monolayers in vitro, and restraint stress-induced barrier dysfunction in mouse colon in vivo. Live cell imaging showed that osmotic stress, cyclic stretch and DSS triggered rapid production of ROS in Caco-2 cell monolayers, which was blocked by depletion of intracellular Ca2+ by BAPTA. Knockdown of CaV1.3 or TRPV6 channels blocked osmotic stress and DSS-induced ROS production and attenuated tight junction disruption and barrier dysfunction. N-acetyl L-cysteine (NAC) and L-nitroarginine methyl ester (L-NAME) blocked stress-induced tight junction disruption and barrier dysfunction. NAC and L-NAME also blocked stress-induced activation of JNK and c-Src. ROS was co-localized with the mitochondrial marker in stressed cells. Cyclosporin A blocked osmotic stress and DSS-induced ROS production, barrier dysfunction, tight junction disruption and JNK activation. Mitochondria-targeted Mito-TEMPO blocked osmotic stress and DSS-induced barrier dysfunction and tight junction disruption. Chronic restraint stress in mice resulted in the elevation of intracellular Ca2+, activation of JNK and c-Src, and disruption of tight junction in the colonic epithelium. Furthermore, corticosterone administration induced JNK and c-Src activation, tight junction disruption and protein thiol oxidation in colonic mucosa. This study demonstrates that oxidative stress is a common signal in the mechanism of tight junction disruption in the intestinal epithelium by different types of cellular stress in vitro and bio behavioral stress in vivo. PMID:28057718

Molecular structure of dextran sulphate sodium in aqueous environment

NASA Astrophysics Data System (ADS)

Yu, Miao; Every, Hayley A.; Jiskoot, Wim; Witkamp, Geert-Jan; Buijs, Wim

2018-03-01

Here we propose a 3D-molecular structural model for dextran sulphate sodium (DSS) in a neutral aqueous environment based on the results of a molecular modelling study. The DSS structure is dominated by the stereochemistry of the 1,6-linked α-glucose units and the presence of two sulphate groups on each α-glucose unit. The structure of DSS can be best described as a helix with various patterns of di-sulphate substitution on the glucose rings. The presence of a side chain does not alter the 3D-structure of the linear main chain much, but affects the overall spatial dimension of the polymer. The simulated polymers have a diameter similar to or in some cases even larger than model α-hemolysin nano-pores for macromolecule transport in many biological processes, indicating a size-limited translocation through such pores. All results of the molecular modelling study are in line with previously reported experimental data. This study establishes the three-dimensional structure of DSS and summarizes the spatial dimension of the polymer, serving as the basis for a better understanding on the molecular level of DSS-involved electrostatic interaction processes with biological components like proteins and cell pores.

The value of daily platelet counts for predicting dengue shock syndrome: Results from a prospective observational study of 2301 Vietnamese children with dengue.

PubMed

Lam, Phung Khanh; Ngoc, Tran Van; Thu Thuy, Truong Thi; Hong Van, Nguyen Thi; Nhu Thuy, Tran Thi; Hoai Tam, Dong Thi; Dung, Nguyen Minh; Hanh Tien, Nguyen Thi; Thanh Kieu, Nguyen Tan; Simmons, Cameron; Wills, Bridget; Wolbers, Marcel

2017-04-01

Dengue is the most important mosquito-borne viral infection to affect humans. Although it usually manifests as a self-limited febrile illness, complications may occur as the fever subsides. A systemic vascular leak syndrome that sometimes progresses to life-threatening hypovolaemic shock is the most serious complication seen in children, typically accompanied by haemoconcentration and thrombocytopenia. Robust evidence on risk factors, especially features present early in the illness course, for progression to dengue shock syndrome (DSS) is lacking. Moreover, the potential value of incorporating serial haematocrit and platelet measurements in prediction models has never been assessed. We analyzed data from a prospective observational study of Vietnamese children aged 5-15 years admitted with clinically suspected dengue to the Hospital for Tropical Diseases in Ho Chi Minh City between 2001 and 2009. The analysis population comprised all children with laboratory-confirmed dengue enrolled between days 1-4 of illness. Logistic regression was the main statistical model for all univariate and multivariable analyses. The prognostic value of daily haematocrit levels and platelet counts were assessed using graphs and separate regression models fitted on each day of illness. Among the 2301 children included in the analysis, 143 (6%) progressed to DSS. Significant baseline risk factors for DSS included a history of vomiting, higher temperature, a palpable liver, and a lower platelet count. Prediction models that included serial daily platelet counts demonstrated better ability to discriminate patients who developed DSS from others, than models based on enrolment information only. However inclusion of daily haematocrit values did not improve prediction of DSS. Daily monitoring of platelet counts is important to help identify patients at high risk of DSS. Development of dynamic prediction models that incorporate signs, symptoms, and daily laboratory measurements, could improve DSS prediction and thereby reduce the burden on health services in endemic areas.

Artificial Intelligence (AI), Operations Research (OR), and Decision Support Systems (DSS): A conceptual framework

NASA Technical Reports Server (NTRS)

Parnell, Gregory S.; Rowell, William F.; Valusek, John R.

1987-01-01

In recent years there has been increasing interest in applying the computer based problem solving techniques of Artificial Intelligence (AI), Operations Research (OR), and Decision Support Systems (DSS) to analyze extremely complex problems. A conceptual framework is developed for successfully integrating these three techniques. First, the fields of AI, OR, and DSS are defined and the relationships among the three fields are explored. Next, a comprehensive adaptive design methodology for AI and OR modeling within the context of a DSS is described. These observations are made: (1) the solution of extremely complex knowledge problems with ill-defined, changing requirements can benefit greatly from the use of the adaptive design process, (2) the field of DSS provides the focus on the decision making process essential for tailoring solutions to these complex problems, (3) the characteristics of AI, OR, and DSS tools appears to be converging rapidly, and (4) there is a growing need for an interdisciplinary AI/OR/DSS education.

How can we make progress with decision support systems in landscape and river basin management? Lessons learned from a comparative analysis of four different decision support systems.

PubMed

Volk, Martin; Lautenbach, Sven; van Delden, Hedwig; Newham, Lachlan T H; Seppelt, Ralf

2010-12-01

This article analyses the benefits and shortcomings of the recently developed decision support systems (DSS) FLUMAGIS, Elbe-DSS, CatchMODS, and MedAction. The analysis elaborates on the following aspects: (i) application area/decision problem, (ii) stakeholder interaction/users involved, (iii) structure of DSS/model structure, (iv) usage of the DSS, and finally (v) most important shortcomings. On the basis of this analysis, we formulate four criteria that we consider essential for the successful use of DSS in landscape and river basin management. The criteria relate to (i) system quality, (ii) user support and user training, (iii) perceived usefulness and (iv) user satisfaction. We can show that the availability of tools and technologies for DSS in landscape and river basin management is good to excellent. However, our investigations indicate that several problems have to be tackled. First of all, data availability and homogenisation, uncertainty analysis and uncertainty propagation and problems with model integration require further attention. Furthermore, the appropriate and methodological stakeholder interaction and the definition of 'what end-users really need and want' have been documented as general shortcomings of all four examples of DSS. Thus, we propose an iterative development process that enables social learning of the different groups involved in the development process, because it is easier to design a DSS for a group of stakeholders who actively participate in an iterative process. We also identify two important lines of further development in DSS: the use of interactive visualization tools and the methodology of optimization to inform scenario elaboration and evaluate trade-offs among environmental measures and management alternatives.

How Can We Make Progress with Decision Support Systems in Landscape and River Basin Management? Lessons Learned from a Comparative Analysis of Four Different Decision Support Systems

NASA Astrophysics Data System (ADS)

Volk, Martin; Lautenbach, Sven; van Delden, Hedwig; Newham, Lachlan T. H.; Seppelt, Ralf

2010-12-01

This article analyses the benefits and shortcomings of the recently developed decision support systems (DSS) FLUMAGIS, Elbe-DSS, CatchMODS, and MedAction. The analysis elaborates on the following aspects: (i) application area/decision problem, (ii) stakeholder interaction/users involved, (iii) structure of DSS/model structure, (iv) usage of the DSS, and finally (v) most important shortcomings. On the basis of this analysis, we formulate four criteria that we consider essential for the successful use of DSS in landscape and river basin management. The criteria relate to (i) system quality, (ii) user support and user training, (iii) perceived usefulness and (iv) user satisfaction. We can show that the availability of tools and technologies for DSS in landscape and river basin management is good to excellent. However, our investigations indicate that several problems have to be tackled. First of all, data availability and homogenisation, uncertainty analysis and uncertainty propagation and problems with model integration require further attention. Furthermore, the appropriate and methodological stakeholder interaction and the definition of `what end-users really need and want' have been documented as general shortcomings of all four examples of DSS. Thus, we propose an iterative development process that enables social learning of the different groups involved in the development process, because it is easier to design a DSS for a group of stakeholders who actively participate in an iterative process. We also identify two important lines of further development in DSS: the use of interactive visualization tools and the methodology of optimization to inform scenario elaboration and evaluate trade-offs among environmental measures and management alternatives.

Keratins Are Altered in Intestinal Disease-Related Stress Responses.

PubMed

Helenius, Terhi O; Antman, Cecilia A; Asghar, Muhammad Nadeem; Nyström, Joel H; Toivola, Diana M

2016-09-10

Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery.

Intravital imaging of mouse colonic adenoma using MMP-based molecular probes with multi-channel fluorescence endoscopy.

PubMed

Oh, Gyungseok; Yoo, Su Woong; Jung, Yebin; Ryu, Yeon-Mi; Park, Youngrong; Kim, Sang-Yeob; Kim, Ki Hean; Kim, Sungjee; Myung, Seung-Jae; Chung, Euiheon

2014-05-01

Intravital imaging has provided molecular, cellular and anatomical insight into the study of tumor. Early detection and treatment of gastrointestinal (GI) diseases can be enhanced with specific molecular markers and endoscopic imaging modalities. We present a wide-field multi-channel fluorescence endoscope to screen GI tract for colon cancer using multiple molecular probes targeting matrix metalloproteinases (MMP) conjugated with quantum dots (QD) in AOM/DSS mouse model. MMP9 and MMP14 antibody (Ab)-QD conjugates demonstrate specific binding to colonic adenoma. The average target-to-background (T/B) ratios are 2.10 ± 0.28 and 1.78 ± 0.18 for MMP14 Ab-QD and MMP9 Ab-QD, respectively. The overlap between the two molecular probes is 67.7 ± 8.4%. The presence of false negative indicates that even more number of targeting could increase the sensitivity of overall detection given heterogeneous molecular expression in tumors. Our approach indicates potential for the screening of small or flat lesions that are precancerous.

Induction of ulcerative colitis in mice influences the course of infection with the nematode Trichuris muris.

PubMed

Vegas-Sánchez, M C; Rollán-Landeras, E; García-Rodríguez, J J; Bolás-Fernández, F

2015-09-01

The aim of this study was to assess the effect of infection with the nematode whipworm Trichuris muris on the course of chemically induced acute ulcerative colitis in CBA/J mice, a strain proven to be highly resistant to infection with T. muris. Each mouse was infected with 50 embryonated eggs of T. muris by oral gavage. Acute colitis was triggered by administering 4% dextran sulphate sodium (DSS) in the drinking water for nine consecutive days at different times after infection. Concurrent infection and DSS administration exacerbate the severity of the colitis while favouring the permanence of parasites in the intestine. The induction of ulcerative colitis from days 54 to 62 post-infection (p.i.), when all worms had been expelled, ameliorated the course of the inflammatory disease. When ulcerative colitis was triggered earlier on, from days 27 to 35 p.i., the beneficial effects on inflammatory events were clearly shown with signs of mucosal epithelization and regeneration as early as day 1 after DSS administration. Previous infections by T. muris therefore accelerate recovery from subsequently induced inflammatory bowel disease and such an effect assists the nematode to persist in the intestinal niche.

A method for integrating multiple components in a decision support system

Treesearch

Donald Nute; Walter D. Potter; Zhiyuan Cheng; Mayukh Dass; Astrid Glende; Frederick Maierv; Cy Routh; Hajime Uchiyama; Jin Wang; Sarah Witzig; Mark Twery; Peter Knopp; Scott Thomasma; H. Michael Rauscher

2005-01-01

We present a flexible, extensible method for integrating multiple tools into a single large decision support system (DSS) using a forest ecosystem management DSS (NED-2) as an example. In our approach, a rich ontology for the target domain is developed and implemented in the internal data model for the DSS. Semi-autonomous agents control external components and...

Partially hydrolyzed guar gum enhances colonic epithelial wound healing via activation of RhoA and ERK1/2.

PubMed

Horii, Yusuke; Uchiyama, Kazuhiko; Toyokawa, Yuki; Hotta, Yuma; Tanaka, Makoto; Yasukawa, Zenta; Tokunaga, Makoto; Okubo, Tsutomu; Mizushima, Katsura; Higashimura, Yasuki; Dohi, Osamu; Okayama, Tetsuya; Yoshida, Naohisa; Katada, Kazuhiro; Kamada, Kazuhiro; Handa, Osamu; Ishikawa, Takeshi; Takagi, Tomohisa; Konishi, Hideyuki; Naito, Yuji; Itoh, Yoshito

2016-07-13

Healing of the intestinal mucosal epithelium was found to be a critical factor in the treatment of inflammatory bowel disease (IBD). In this study, we provide further evidence that partially hydrolyzed dietary fiber (PHGG) enhances colonic epithelial cell wound healing, and partially characterize the mechanism that governs this process. Young adult mouse colonic (YAMC) epithelial cells were scraped with a 10 μl micro-pipette tip to denude a round of the monolayer and were incubated with PHGG. The area of cell migration was measured using Image J software. Meanwhile, Rho activation assays were utilized to monitor Rho activation levels. To assess in vivo effects, C57B6 mice were treated with DSS for 7 days and then provided food supplemented with PHGG for 8 days. YAMC cells treated with PHGG exhibited significantly enhanced wound healing compared to the control cells; however, this enhancement was inhibited by both Y-27632 (RhoA inhibitor) and U0126 (ERK1/2 inhibitor). Likewise, there was a PHGG-dependent increase in F-actin accumulation and Rho kinase activity that was blocked by U0126. Meanwhile, PHGG-dependent ERK1/2 activity was not inhibited by Y-27632. In the DSS-induced mouse colitis model, animals that received food supplemented with PHGG exhibited significant recovery of the colonic mucosa. In this study, we demonstrate that PHGG promotes colonic epithelial cell wound healing via activation of RhoA, which occurs downstream of ERK1/2 activation. These findings indicate that PHGG could be utilized as a therapeutic agent for patients with intestinal mucosal damage such as those with IBD.

Summed and Weighted Summary Scores for the Medsger Disease Severity Scale Compared with the Physician's Global Assessment of Disease Severity in Systemic Sclerosis.

PubMed

Harel, Daphna; Hudson, Marie; Iliescu, Alexandra; Baron, Murray; Steele, Russell

2016-08-01

To develop a weighted summary score for the Medsger Disease Severity Scale (DSS) and to compare its measurement properties with those of a summed DSS score and a physician's global assessment (PGA) of severity score in systemic sclerosis (SSc). Data from 875 patients with SSc enrolled in a multisite observational research cohort were extracted from a central database. Item response theory was used to estimate weights for the DSS weighted score. Intraclass correlation coefficients (ICC) and convergent, discriminative, and predictive validity of the 3 summary measures in relation to patient-reported outcomes (PRO) and mortality were compared. Mean PGA was 2.69 (SD 2.16, range 0-10), mean DSS summed score was 8.60 (SD 4.02, range 0-36), and mean DSS weighted score was 8.11 (SD 4.05, range 0-36). ICC were similar for all 3 measures [PGA 6.9%, 95% credible intervals (CrI) 2.1-16.2; DSS summed score 2.5%, 95% CrI 0.4-6.7; DSS weighted score 2.0%, 95% CrI 0.1-5.6]. Convergent and discriminative validity of the 3 measures for PRO were largely similar. In Cox proportional hazards models adjusting for age and sex, the 3 measures had similar predictive ability for mortality (adjusted R(2) 13.9% for PGA, 12.3% for DSS summed score, and 10.7% DSS weighted score). The 3 summary scores appear valid and perform similarly. However, there were some concerns with the weights computed for individual DSS scales, with unexpected low weights attributed to lung, heart, and kidney, leading the PGA to be the preferred measure at this time. Further work refining the DSS could improve the measurement properties of the DSS summary scores.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Haixia; Zhang, Xinhua; Chen, Xuewei

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

A Novel Modification of the AOM/DSS Model for Inducing Intestinal Adenomas in Mice.

PubMed

Angelou, Anastasios; Andreatos, Nikolaos; Antoniou, Efstathios; Zacharioudaki, Argiro; Theodoropoulos, George; Damaskos, Christos; Garmpis, Nikolaos; Yuan, Chunhui; Xiao, Weidong; Theocharis, Stamatios; Zografos, George; Papalois, Apostolos; Margonis, Georgios Antonios

2018-06-01

Our aim was to develop an animal model of the precancerous stages of colitis-associated carcinogenesis by modifying the established azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Six mice were treated with varying cycles of DSS following AOM administration as above (group 1: three mice received three 5-day cycles of 3.0% DSS and group 2: three mice received three 7-day cycles of 2.5% DSS; every cycle was followed by a 2-week rest period) and were sacrificed on day 84 of the experiment. By contrast, three female C57BL6 mice (group 3) were treated with a single intraperitoneal dose (10 mg/kg of body weight) of AOM followed by three 5-day cycles of oral 2.5% DSS, with each cycle interrupted by a 2-week rest period. The mice of this group were sacrificed at 60 days. In groups 1 and 2, cancer was noted in five out of the six mice. In group 3, adenomas with dysplastic lesions were noted in all of the mice, but none had developed adenocarcinoma. Our results suggest that the administration of three 5-day cycles of 2.5% DSS following an initial dose of AOM may successfully induce adenoma formation without the concurrent presence of carcinoma in female C57BL6 mice that are sacrificed on experimental day 60. In turn, this modification of the widely used AOM/DSS protocol may constitute a novel approach for investigating colitis-related colonic adenomas. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

PubMed

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

2018-01-01

Inflammatory bowel diseases (IBD) are a group of chronic inflammatory disorders of the intestine, with as-yet-unclear etiologies, affecting over a million people in the United States alone. With the emergence of microbiome research, numerous studies have shown a connection between shifts in the gut microbiota composition (dysbiosis) and patterns of IBD development. In a previous study, we showed that interleukin 1α (IL-1α) deficiency in IL-1α knockout (KO) mice results in moderate dextran sodium sulfate (DSS)-induced colitis compared to that of wild-type (WT) mice, characterized by reduced inflammation and complete healing, as shown by parameters of weight loss, disease activity index (DAI) score, histology, and cytokine expression. In this study, we tested whether the protective effects of IL-1α deficiency on DSS-induced colitis correlate with changes in the gut microbiota and whether manipulation of the microbiota by cohousing can alter patterns of colon inflammation. We analyzed the gut microbiota composition in both control (WT) and IL-1α KO mice under steady-state homeostasis, during acute DSS-induced colitis, and after recovery using 16S rRNA next-generation sequencing. Additionally, we performed cohousing of both mouse groups and tested the effects on the microbiota and clinical outcomes. We demonstrate that host-derived IL-1α has a clear influence on gut microbiota composition, as well as on severity of DSS-induced acute colon inflammation. Cohousing both successfully changed the gut microbiota composition and increased the disease severity of IL-1α-deficient mice to levels similar to those of WT mice. This study shows a strong and novel correlation between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. IMPORTANCE Here, we show a connection between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. Specifically, we show that the mild colitis symptoms seen in IL-1α-deficient mice following administration of DSS are correlated with the unique gut microbiota compositions of the mice. However, when these mice are exposed to WT microbiota by cohousing, their gut microbiota composition returns to resemble that of WT mice, and their disease severity increases significantly. As inflammatory bowel diseases are such common diseases, with limited effective treatments to date, there is a great need to better understand the interactions between microbiota composition, the immune system, and colitis. This study shows correlation between microbiota composition and DSS resistance; it may potentially lead to the development of improved probiotics for IBD treatment.

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

PubMed Central

2018-01-01

ABSTRACT Inflammatory bowel diseases (IBD) are a group of chronic inflammatory disorders of the intestine, with as-yet-unclear etiologies, affecting over a million people in the United States alone. With the emergence of microbiome research, numerous studies have shown a connection between shifts in the gut microbiota composition (dysbiosis) and patterns of IBD development. In a previous study, we showed that interleukin 1α (IL-1α) deficiency in IL-1α knockout (KO) mice results in moderate dextran sodium sulfate (DSS)-induced colitis compared to that of wild-type (WT) mice, characterized by reduced inflammation and complete healing, as shown by parameters of weight loss, disease activity index (DAI) score, histology, and cytokine expression. In this study, we tested whether the protective effects of IL-1α deficiency on DSS-induced colitis correlate with changes in the gut microbiota and whether manipulation of the microbiota by cohousing can alter patterns of colon inflammation. We analyzed the gut microbiota composition in both control (WT) and IL-1α KO mice under steady-state homeostasis, during acute DSS-induced colitis, and after recovery using 16S rRNA next-generation sequencing. Additionally, we performed cohousing of both mouse groups and tested the effects on the microbiota and clinical outcomes. We demonstrate that host-derived IL-1α has a clear influence on gut microbiota composition, as well as on severity of DSS-induced acute colon inflammation. Cohousing both successfully changed the gut microbiota composition and increased the disease severity of IL-1α-deficient mice to levels similar to those of WT mice. This study shows a strong and novel correlation between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. IMPORTANCE Here, we show a connection between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. Specifically, we show that the mild colitis symptoms seen in IL-1α-deficient mice following administration of DSS are correlated with the unique gut microbiota compositions of the mice. However, when these mice are exposed to WT microbiota by cohousing, their gut microbiota composition returns to resemble that of WT mice, and their disease severity increases significantly. As inflammatory bowel diseases are such common diseases, with limited effective treatments to date, there is a great need to better understand the interactions between microbiota composition, the immune system, and colitis. This study shows correlation between microbiota composition and DSS resistance; it may potentially lead to the development of improved probiotics for IBD treatment. PMID:29766049

The Source of the Symbolic Numerical Distance and Size Effects

PubMed Central

Krajcsi, Attila; Lengyel, Gábor; Kojouharova, Petia

2016-01-01

Human number understanding is thought to rely on the analog number system (ANS), working according to Weber’s law. We propose an alternative account, suggesting that symbolic mathematical knowledge is based on a discrete semantic system (DSS), a representation that stores values in a semantic network, similar to the mental lexicon or to a conceptual network. Here, focusing on the phenomena of numerical distance and size effects in comparison tasks, first we discuss how a DSS model could explain these numerical effects. Second, we demonstrate that the DSS model can give quantitatively as appropriate a description of the effects as the ANS model. Finally, we show that symbolic numerical size effect is mainly influenced by the frequency of the symbols, and not by the ratios of their values. This last result suggests that numerical distance and size effects cannot be caused by the ANS, while the DSS model might be the alternative approach that can explain the frequency-based size effect. PMID:27917139

Dextran sulphate sodium (DSS) causes intestinal histopathology and inflammatory changes consistent with increased gut leakiness in chickens.

PubMed

Zou, X; Ji, J; Wang, J; Qu, H; Shu, D M; Guo, F Y; Luo, C L

2018-04-01

1. The clinical severity, histological changes, indicators of gut leakiness and inflammatory cytokine profiles were studied in chickens with dextran sulphate sodium (DSS)-induced intestinal inflammation. 2. The experimental groups (1.25%, 1.5% and 2.5% DSS) showed clinical signs, such as loose stools and weight loss, which increased with additional treatment days and, as expected, the effects of DSS-induced intestinal inflammation were time and dose-dependent. 3. After 10 d, histological manifestations were evident, including goblet cell depletion, mucus layer loss, significantly shorter villi and a thinner total ileal mucosa. 4. The d(-)-lactate value, which was used as a gut leakiness indicator, was significantly increased in the 2.5% DSS group. 5. Expression of the inflammatory cytokines interleukin-1Beta, tumour necrosis factor alpha and interleukin-10 in the serum significantly increased with DSS treatment. 6. This study indicates that the experimental intestinal inflammation induced by DSS is an ideal model to study the pathogenic mechanisms of intestinal inflammation in chickens and to test the efficacy of therapies.

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

PubMed

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

2010-10-21

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

New Perspective on Dextran Sodium Sulfate Colitis: Antigen-Specific T Cell Development during Intestinal Inflammation

PubMed Central

Morgan, Mary E.; Zheng, Bin; Koelink, Pim J.; van de Kant, Hendrick J. G.; Haazen, Lizette C. J. M.; van Roest, Manon; Garssen, Johan; Folkerts, Gert; Kraneveld, Aletta D.

2013-01-01

CD4+ T cell responses against oral antigens can develop in inflammatory bowel disease (IBD) patients, which may modulate disease. Dextran sodium sulfate (DSS) colitis is commonly used to study IBD, however, it is not considered the best model in which to study T cell involvement in intestinal disease. Our aim was to determine if antigen-specific T cells could be induced during DSS colitis and if they could be detected after disease resolution. To induce antigen-specific T cells, the tracking antigen, ovalbumin (OVA), was administered orally during colitis initiation. Disease severity was monitored, and the antigen-reactivity of CD4+ T cells examined using CD69 expression. While OVA-directed, CD4+ Foxp3+ regulatory T cells could be detected in the spleens of both OVA-treated control and DSS mice, OVA-reactive, CD4+ Foxp3-T cells were only found in the OVA and DSS-treated mice. These results indicate that during DSS colitis T cells develop that are specific against oral antigens, and they are found systemically after colitis resolution. This gives added depth and utility to the DSS model as well as a way to track T cells that are primed against luminal antigens. PMID:23936123

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

PubMed Central

Constante, Marco; Fragoso, Gabriela; Calvé, Annie; Samba-Mondonga, Macha; Santos, Manuela M.

2017-01-01

Dietary heme can be used by colonic bacteria equipped with heme-uptake systems as a growth factor and thereby impact on the microbial community structure. The impact of heme on the gut microbiota composition may be particularly pertinent in chronic inflammation such as in inflammatory bowel disease (IBD), where a strong association with gut dysbiosis has been consistently reported. In this study we investigated the influence of dietary heme on the gut microbiota and inferred metagenomic composition, and on chemically induced colitis and colitis-associated adenoma development in mice. Using 16S rRNA gene sequencing, we found that mice fed a diet supplemented with heme significantly altered their microbiota composition, characterized by a decrease in α-diversity, a reduction of Firmicutes and an increase of Proteobacteria, particularly Enterobacteriaceae. These changes were similar to shifts seen in dextran sodium sulfate (DSS)-treated mice to induce colitis. In addition, dietary heme, but not systemically delivered heme, contributed to the exacerbation of DSS-induced colitis and facilitated adenoma formation in the azoxymethane/DSS colorectal cancer (CRC) mouse model. Using inferred metagenomics, we found that the microbiota alterations elicited by dietary heme resulted in non-beneficial functional shifts, which were also characteristic of DSS-induced colitis. Furthermore, a reduction in fecal butyrate levels was found in mice fed the heme supplemented diet compared to mice fed the control diet. Iron metabolism genes known to contribute to heme release from red blood cells, heme uptake, and heme exporter proteins, were significantly enriched, indicating a shift toward favoring the growth of bacteria able to uptake heme and protect against its toxicity. In conclusion, our data suggest that luminal heme, originating from dietary components or gastrointestinal bleeding in IBD and, to lesser extent in CRC, directly contributes to microbiota dysbiosis. Thus, luminal heme levels may further exacerbate colitis through the modulation of the gut microbiota and its metagenomic functional composition. Our data may have implications in the development of novel targets for therapeutic approaches aimed at lowering gastrointestinal heme levels through heme chelation or degradation using probiotics and nutritional interventions. PMID:28983289

AVX-470: A Novel Oral Anti-TNF Antibody with Therapeutic Potential in Inflammatory Bowel Disease

PubMed Central

Bhol, Kailash C.; Tracey, Daniel E.; Lemos, Brenda R.; Lyng, Gregory D.; Erlich, Emma C.; Keane, David M.; Quesenberry, Michael S.; Holdorf, Amy D.; Schlehuber, Lisa D.; Clark, Shawn A.; Fox, Barbara S.

2013-01-01

Background Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the GI tract that is currently treated with injected monoclonal antibodies specific for tumor necrosis factor (TNF). We developed and characterized AVX-470, a novel polyclonal antibody specific for human TNF. We evaluated the oral activity of AVX-470m, a surrogate antibody specific murine TNF, in several well-accepted mouse models of IBD. Methods AVX-470 and AVX-470m were isolated from the colostrum of dairy cows that had been immunized with TNF. The potency, specificity and affinity of both AVX-470 and AVX-470m were evaluated in vitro and compared with infliximab. AVX-470m was orally administered to mice either before or after induction of colitis and activity was measured by endoscopy, histopathology, immunohistochemistry and quantitative measurement of mRNA levels. Colitis was induced using either 2,4,6-trinitrobenzene sulfonate (TNBS) or dextran sodium sulfate (DSS). Results AVX-470 and AVX-470m were shown to be functionally comparable in vitro. Moreover, the specificity, neutralizing potency and affinity of AVX-470 were comparable to infliximab. Orally administered AVX-470m effectively reduced disease severity in several mouse models of IBD. Activity was comparable to that of oral prednisolone or parenteral etanercept. The antibody penetrated the colonic mucosa and inhibited TNF-driven mucosal inflammation with minimal systemic exposure. Conclusions AVX-470 is a novel polyclonal anti-TNF antibody with an in vitro activity profile comparable to that of infliximab. Oral administration of a surrogate antibody specific for mouse TNF is effective in treating mouse models of IBD, delivering the anti-TNF to the site of inflammation with minimal systemic exposure. PMID:23949620

In Inflamed Intestinal Tissues and Epithelial Cells, Interleukin 22 Signaling Increases Expression of H19 Long Noncoding RNA, Which Promotes Mucosal Regeneration.

PubMed

Geng, Hua; Bu, Heng-Fu; Liu, Fangyi; Wu, Longtao; Pfeifer, Karl; Chou, Pauline M; Wang, Xiao; Sun, Jiaren; Lu, Lu; Pandey, Ashutosh; Bartolomei, Marisa S; De Plaen, Isabelle G; Wang, Peng; Yu, Jindan; Qian, Jiaming; Tan, Xiao-Di

2018-04-03

Inflammation affects regeneration of the intestinal epithelia; long non-coding RNAs (lncRNAs) regulate cell functions, such as proliferation, differentiation, and migration. We investigated the mechanisms by which the lncRNA H19, imprinted maternally expressed transcript (H19) regulates regeneration of intestinal epithelium using cell cultures and mouse models of inflammation. We performed RNA-sequencing transcriptome analyses of intestinal tissues from mice with lipopolysaccharide (LPS)-induced sepsis to identify lncRNAs associated with inflammation; findings were confirmed by quantitative real-time polymerase chain reaction and in situ hybridization analyses of intestinal tissues from mice with sepsis or dextran sulfate sodium (DSS)-induced mucosal wound healing and patients with ulcerative colitis compared to healthy individuals (controls). We screened cytokines for their ability to induce expression of H19 in HT-29 cells and intestinal epithelial cells (IECs), and confirmed findings in crypt epithelial organoids derived from mouse small intestine. IECs were incubated with different signal transduction inhibitors and effects on H19 lncRNA levels were measured. We assessed intestinal epithelial proliferation or regeneration in H19 ΔEx1/+ mice given LPS or DSS vs wild-type littermates (control mice). H19 was overexpressed in IECs using lentiviral vectors and cell proliferation was measured. We performed RNA antisense purification, RNA immunoprecipitation, and luciferase reporter assays to study functions of H19 in IECs. In RNA-sequencing transcriptome analysis of lncRNA expression in intestinal tissues from mice, we found levels of H19 only changed significantly with LPS exposure. Levels of H19 lncRNA increased in intestinal tissues of patients with ulcerative colitis, mice with LPS-induced sepsis, or mice with DSS-induced colitis, compared with controls. Increased H19 lncRNA localized to epithelial cells in the intestine, regardless of Lgr5 messenger RNA expression. Exposure of IECs to interleukin (IL) 22 increased levels of H19 lncRNA with time and dose, which required STAT3 and protein kinase A activity. IL22 induced expression of H19 in mouse intestinal epithelial organoids within 6 hours. Exposure to IL22 increased growth of intestinal epithelial organoids derived from control mice, but not H19 ΔEx1/+ mice. Overexpression of H19 in HT-29 cells increased their proliferation. Intestinal mucosa healed more slowly after withdrawal of DSS from H19 ΔEx1/+ mice vs control mice. Crypt epithelial cells from H19 ΔEx1/+ mice proliferated more slowly than those from control mice after exposure to LPS. H19 lncRNA bound to p53 and microRNAs that inhibit cell proliferation, including microRNA 34a and let-7; H19 lncRNA binding blocked their function, leading to increased expression of genes that promote regeneration of the epithelium. The level of lncRNA H19 is increased in inflamed intestinal tissues from mice and patients. The inflammatory cytokine IL22 induces expression of H19 in IECs, which is required for intestinal epithelial proliferation and mucosal healing. H19 lncRNA appears to inhibit p53 protein and microRNA 34a and let-7 to promote proliferation of IECs and epithelial regeneration. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Prognostic model for survival in patients with early stage cervical cancer.

PubMed

Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R

2011-02-15

In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.

Opposing roles of nuclear receptor HNF4α isoforms in colitis and colitis-associated colon cancer

PubMed Central

Chellappa, Karthikeyani; Deol, Poonamjot; Evans, Jane R; Vuong, Linh M; Chen, Gang; Briançon, Nadege; Bolotin, Eugene; Lytle, Christian; Nair, Meera G; Sladek, Frances M

2016-01-01

HNF4α has been implicated in colitis and colon cancer in humans but the role of the different HNF4α isoforms expressed from the two different promoters (P1 and P2) active in the colon is not clear. Here, we show that P1-HNF4α is expressed primarily in the differentiated compartment of the mouse colonic crypt and P2-HNF4α in the proliferative compartment. Exon swap mice that express only P1- or only P2-HNF4α have different colonic gene expression profiles, interacting proteins, cellular migration, ion transport and epithelial barrier function. The mice also exhibit altered susceptibilities to experimental colitis (DSS) and colitis-associated colon cancer (AOM+DSS). When P2-HNF4α-only mice (which have elevated levels of the cytokine resistin-like β, RELMβ, and are extremely sensitive to DSS) are crossed with Retnlb-/- mice, they are rescued from mortality. Furthermore, P2-HNF4α binds and preferentially activates the RELMβ promoter. In summary, HNF4α isoforms perform non-redundant functions in the colon under conditions of stress, underscoring the importance of tracking them both in colitis and colon cancer. DOI: http://dx.doi.org/10.7554/eLife.10903.001 PMID:27166517

Keratins Are Altered in Intestinal Disease-Related Stress Responses

PubMed Central

Helenius, Terhi O.; Antman, Cecilia A.; Asghar, Muhammad Nadeem; Nyström, Joel H.; Toivola, Diana M.

2016-01-01

Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery. PMID:27626448

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

PubMed Central

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

2010-01-01

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

Computer-Mediated Counter-Arguments and Individual Learning

ERIC Educational Resources Information Center

Hsu, Jack Shih-Chieh; Huang, Hsieh-Hong; Linden, Lars P.

2011-01-01

This study explores a de-bias function for a decision support systems (DSS) that is designed to help a user avoid confirmation bias by increasing the user's learning opportunities. Grounded upon the theory of mental models, the use of DSS is viewed as involving a learning process, whereby a user is directed to build mental models so as to reduce…

Age-related slowing of digit symbol substitution revisited: what do longitudinal age changes reflect?

PubMed

MacDonald, Stuart W S; Hultsch, David F; Strauss, Esther; Dixon, Roger A

2003-05-01

A previous investigation reported that cross-sectional age differences in Digit Symbol Substitution (DSS) test performance reflect declines in perceptual processing speed. Support for the tenability of the processing speed hypothesis requires examining whether longitudinal age-related change in DSS performance is largely mediated by changes in speed. The present study used data from the Victoria Longitudinal Study to examine patterns and predictors of longitudinal change in DSS for 512 older adults (M(age) = 68.37 years, SD = 7.43). On the basis of multilevel modeling, baseline DSS performance was poorer for older participants and men, with longitudinal declines more pronounced with increasing age and decreasing speed. In contrast to the present cross-sectional findings, statistical control of change trajectories in perceptual speed using the same data did not substantially attenuate age changes. These discrepancies suggest different sources of variance may underlie cross-sectional age differences and longitudinal age changes for DSS.

Suppressive Effect of Zinc on the Formation of Colonic Preneoplastic Lesions in the Mouse Fed High Levels of Dietary Iron

PubMed Central

Park, Hyunji; Kang, Bong Su; Kim, Dang Young; Yoon, Ja Seon; Jeong, Jae-Hwang; Nam, Sang Yoon; Yun, Young Won

2012-01-01

We investigated the effect of zinc on the formation of colonic aberrant crypt foci induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in mice with high iron diet (HFe; 450 ppm iron). Sixweek old ICR mice were fed on high iron diets with combination of three different levels of zinc in diets, low-zinc (LZn; 0.01 ppm), medium-zinc (MZn; 0.1 ppm), and high-zinc (HZn; 1 ppm) for 12 weeks. Animals were received weekly intraperitoneal injections of AOM (10 mg/kg B.W. in saline) for 3 weeks followed by 2% DSS (molecular weight 36,000~50,000) in the drinking water for a week. To confirm the iron storage in the body, the hepatic iron concentration has been determine chemically and compared with histological assessment visualized by Prussian blue reaction. Aberrant crypt (AC) and aberrant crypt foci (ACF) were analyzed in the colonic mucosa of mouse fed high dietary iron. Superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) level were also investigated. Apoptosis in the preneoplastic lesion was determined by terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL). In addition, immunohistochemistry of β-catenin was also performed on the mucous membrane of colon. The number of large ACF (≥ 4 AC/ACF), which possess greater tumorigenic potential, was significantly lower in MZn and HZn groups compared with LZn group. Cytosolic SOD activity in the liver was significantly higher in HZn group compared with LZn group. Hepatic MDA level was decreased significantly in HZn group compared with MZn and LZn groups. Apoptotic index was significantly higher in HZn group. Taken together, these findings indicate that dietary zinc might exert a protective effect against colonic preneoplastic lesion induced by AOM/DSS in ICR mice with high iron status, and suggest that dietary supplement of zinc might play a role in suppressing colon carcinogenesis in mice. PMID:24278588

An iterative requirements specification procedure for decision support systems.

PubMed

Brookes, C H

1987-08-01

Requirements specification is a key element in a DSS development project because it not only determines what is to be done, it also drives the evolution process. A procedure for requirements elicitation is described that is based on the decomposition of the DSS design task into a number of functions, subfunctions, and operators. It is postulated that the procedure facilitates the building of a DSS that is complete and integrates MIS, modelling and expert system components. Some examples given are drawn from the health administration field.

A DSS for sustainable development and environmental protection of agricultural regions.

PubMed

Manos, Basil D; Papathanasiou, Jason; Bournaris, Thomas; Voudouris, Kostas

2010-05-01

This paper presents a decision support system (DSS) for sustainable development and environmental protection of agricultural regions developed in the framework of the Interreg-Archimed project entitled WaterMap (development and utilization of vulnerability maps for the monitoring and management of groundwater resources in the ARCHIMED areas). Its aim is to optimize the production plan of an agricultural region taking in account the available resources, the environmental parameters, and the vulnerability map of the region. The DSS is based on an optimization multicriteria model. The spatial integration of vulnerability maps in the DSS enables regional authorities to design policies for optimal agricultural development and groundwater protection from the agricultural land uses. The DSS can further be used to simulate different scenarios and policies by the local stakeholders due to changes on different social, economic, and environmental parameters. In this way, they can achieve alternative production plans and agricultural land uses as well as to estimate economic, social, and environmental impacts of different policies. The DSS is computerized and supported by a set of relational databases. The corresponding software has been developed in a Microsoft Windows XP platform, using Microsoft Visual Basic, Microsoft Access, and the LINDO library. For demonstration reasons, the paper includes an application of the DSS in a region of Northern Greece.

Experimental colitis is exacerbated by concomitant infection with Mycobacterium avium ssp. paratuberculosis.

PubMed

Suwandi, Abdulhadi; Bargen, Imke; Roy, Bishnudeo; Pils, Marina C; Krey, Martina; Zur Lage, Susanne; Basler, Tina; Rohde, Manfred; Falk, Christine S; Hornef, Mathias W; Goethe, Ralph; Weiss, Siegfried

2014-11-01

Crohn's disease (CD) is a chronic inflammatory disorder of the human gastrointestinal tract. Although genetic, immunological, environmental, and bacterial factors have been implicated, the pathogenesis is incompletely understood. The histopathological appearance of CD strikingly resembles Johne's disease, a ruminant inflammatory bowel disease, caused by Mycobacterium avium ssp. paratuberculosis (MAP), but a causative role of MAP in CD has not been established. In this work, we hypothesized that MAP might exacerbate an already existing intestinal disease. We combined dextran sulfate sodium (DSS)-induced colitis with MAP infection in mice and monitored the immune response and bacterial count in different organs. An increased size of liver and spleen was observed in DSS-treated and MAP-infected animals (DSS + MAP) as compared with DSS-treated uninfected (DSS + PBS) mice. Similarly, DSS treatment increased the number and size of MAP-induced liver granulomas and enhanced the MAP counts in enteric tissue. MAP infection in turn delayed the mucosal healing of DSS-induced tissue damage. Finally, high numbers of MAP were found in mesenteric fat tissue causing large granuloma and necrotic regions. Taken together, we present an in vivo model to study the role of MAP infection in CD. Our results confirm the hypothesis that MAP is able to exacerbate existing intestinal inflammation.

Heterobivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

DTIC Science & Technology

2011-04-01

specific membrane antigen (PSMA), showed promise in the clinic for identifying candidates for salvage radiotherapy. (4, 5) Because of the important...removed benzyl group to afford the Lys- Urea-Glu 14 in 85% yield. Compound 14 was conjugated with the suberic acid bis-(N- hydroxysuccinimide ( DSS ) in...directed against human and mouse prostate-specific membrane antigen. Prostate 2004; 61: 1-11. 4. Chang SS, Heston WD. The clinical role of prostate

Lactobacillus acidophilus Suppresses Colitis-Associated Activation of the IL-23/Th17 Axis

PubMed Central

Chen, Linlin; Zou, Yiyou; Peng, Jie; Lu, Fanggen; Yin, Yani; Li, Fujun; Yang, Junwen

2015-01-01

The aim of this paper is to determine the modulatory effects of Lactobacillus acidophilus on the IL-23/Th17 immune axis in experimental colitis. DSS-induced mouse models of UC were to be saline, hormones, and different concentrations of Lactobacillus acidophilus intervention. The expression of interleukin- (IL-) 17, tumor necrosis factor α (TNFα), IL-23, transforming growth factor β1 (TGFβ1), signal transducer and activator of transcription 3 (STAT3), and phosphorylated (p)-STAT3 was examined by RT-PCR, Western blotting, and immunohistochemical analysis. And the results showed that administration of L. acidophilus suppressed Th17 cell-mediated secretion of proinflammatory cytokine IL-17 through downregulation of IL-23 and TGFβ1 expression and downstream phosphorylation of p-STAT3. PMID:25973440

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

PubMed

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

2016-08-01

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

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

PubMed

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

2018-06-11

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

Comparison of multiple enzyme activatable near infrared fluorescent molecular probes for detection and quantification of inflammation in murine colitis models

PubMed Central

Ding, Shengli; Blue, Randal E.; Morgan, Douglas R.; Lund, Pauline K.

2015-01-01

Background Activatable near-infrared fluorescent (NIRF) probes have been used for ex vivo and in vivo detection of intestinal tumors in animal models. We hypothesized that NIRF probes activatable by cathepsins or MMPs will detect and quantify dextran sulphate sodium (DSS) induced acute colonic inflammation in wild type (WT) mice or chronic colitis in IL-10 null mice ex vivo or in vivo. Methods WT mice given DSS, water controls and IL-10 null mice with chronic colitis were administered probes by retro-orbital injection. FMT2500 LX system imaged fresh and fixed intestine ex vivo and mice in vivo. Inflammation detected by probes was verified by histology and colitis scoring. NIRF signal intensity was quantified using 2D region of interest (ROI) ex vivo or 3D ROI-analysis in vivo. Results Ex vivo, seven probes tested yielded significant higher NIRF signals in colon of DSS treated mice versus controls. A subset of probes was tested in IL-10 null mice and yielded strong ex vivo signals. Ex vivo fluorescence signal with 680 series probes was preserved after formalin fixation. In DSS and IL-10 null models, ex vivo NIRF signal strongly and significantly correlated with colitis scores. In vivo, ProSense680, CatK680FAST and MMPsense680 yielded significantly higher NIRF signals in DSS treated mice than controls but background was high in controls. Conclusion Both cathepsin or MMP-activated NIRF-probes can detect and quantify colonic inflammation ex vivo. ProSense680 yielded the strongest signals in DSS colitis ex vivo and in vivo, but background remains a problem for in vivo quantification of colitis. PMID:24374874

Vasoactive Intestinal Peptide Nanomedicine for the Management of Inflammatory Bowel Disease.

PubMed

Jayawardena, Dulari; Anbazhagan, Arivarasu N; Guzman, Grace; Dudeja, Pradeep K; Onyuksel, Hayat

2017-11-06

Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine, with increasing incidence worldwide. At present, the management of IBD is an unmet medical need due to the ineffectiveness of currently available drugs in treating all patients, and there is strong demand for novel therapeutics. In this regard, vasoactive intestinal peptide, a potent anti-inflammatory endogenous hormone, has shown promise in managing multiple immune disorders in animal models. However, when administered in the free form, VIP undergoes rapid degradation in vivo, and with continuous infusion, it causes severe dose limiting side effects. To overcome these barriers, we have developed a superior mode to deliver VIP in its native form, using sterically stabilized micelles (VIP-SSM). Our previous studies demonstrated that, VIP, when administered in SSM, prevented joint damage and inflammation in a mouse model of rheumatoid arthritis at a significantly lower dose than the free peptide, completely abrogating the serious side effect of hypotension associated with VIP. In the current study, we demonstrate the therapeutic benefit of VIP-SSM over free peptide in reversing severe colitis associated with IBD. First, we conducted preliminary studies with dextran sulfate sodium (DSS) induced colitis in mice, to determine the effectiveness of VIP administered on alternate days in reducing disease severity. Thereafter, a single intra peritoneal injection of VIP-SSM or the free peptide was used to determine its therapeutic effect on the reversal of colitis and associated diarrhea. The results demonstrated that when administered on alternate days, both VIP-SSM and VIP were capable of alleviating DSS colitis in mice. However, when administered as a single dose, in a therapeutic setting, VIP-SSM showed superior benefits compared to the free peptide in ameliorating colitis phenotype. Namely, the loss of solid fecal pellets and increased fluid accumulation in colon resulting from DSS insult was abrogated in VIP-SSM treated mice and not with free VIP. Furthermore, reduced protein and mRNA levels of the major chloride bicarbonate exchanger, down regulated in adenoma (DRA), seen with DSS was reversed with VIP-SSM, but not with the free peptide. Similarly, VIP-SSM treatment significantly reduced the elevated mRNA levels of pro-inflammatory cytokines and showed significant histologic recovery when compared to mice treated with free VIP. Therefore, these results demonstrated that as a single dose, the anti-inflammatory and antidiarrheal effects of VIP can be achieved effectively when administered as a nanomedicine. Therefore, we propose VIP-SSM to be developed as a potential therapeutic tool for treating ulcerative colitis, a type of IBD.

Evaluation of Internet-Based Clinical Decision Support Systems

PubMed Central

Thomas, Karl W; Dayton, Charles S

1999-01-01

Background Scientifically based clinical guidelines have become increasingly used to educate physicians and improve quality of care. While individual guidelines are potentially useful, repeated studies have shown that guidelines are ineffective in changing physician behavior. The Internet has evolved as a potentially useful tool for guideline education, dissemination, and implementation because of its open standards and its ability to provide concise, relevant clinical information at the location and time of need. Objective Our objective was to develop and test decision support systems (DSS) based on clinical guidelines which could be delivered over the Internet for two disease models: asthma and tuberculosis (TB) preventive therapy. Methods Using open standards of HTML and CGI, we developed an acute asthma severity assessment DSS and a preventative tuberculosis treatment DSS based on content from national guidelines that are recognized as standards of care. Both DSS's are published on the Internet and operate through a decision algorithm developed from the parent guidelines with clinical information provided by the user at the point of clinical care. We tested the effectiveness of each DSS in influencing physician decisions using clinical scenario testing. Results We first validated the asthma algorithm by comparing asthma experts' decisions with the decisions reached by nonpulmonary nurses using the computerized DSS. Using the DSS, nurses scored the same as experts (89% vs. 88%; p = NS). Using the same scenario test instrument, we next compared internal medicine residents using the DSS with residents using a printed version of the National Asthma Education Program-2 guidelines. Residents using the computerized DSS scored significantly better than residents using the paper-based guidelines (92% vs. 84%; p <0.002). We similarly compared residents using the computerized TB DSS to residents using a printed reference card; the residents using the computerized DSS scored significantly better (95.8% vs. 56.6% correct; p<0.001). Conclusions Previous work has shown that guidelines disseminated through traditional educational interventions have minimal impact on physician behavior. Although computerized DSS have been effective in altering physician behavior, many of these systems are not widely available. We have developed two clinical DSS's based on national guidelines and published them on the Internet. Both systems improved physician compliance with national guidelines when tested in clinical scenarios. By providing information that is coupled to relevant activity, we expect that these widely available DSS's will serve as effective educational tools to positively impact physician behavior. PMID:11720915

Chemopreventive effect of dietary glutamine on colitis-associated colon tumorigenesis in mice.

PubMed

Tian, Yun; Wang, Keming; Wang, Zhaoxia; Li, Nan; Ji, Guozhong

2013-07-01

Chronic colonic inflammation is a known risk factor for colorectal cancer (CRC). Glutamine (GLN) supplementation has shown its anti-inflammation benefit in experimental colitis. Whether GLN is effective in preventing colon carcinogenesis remains to be investigated. The chemopreventive activity of GLN was evaluated in the mouse model of dextran sulfate sodium (DSS)/azoxymethane (AOM)-induced colitis-associated CRC in this study. Mice were treated with DSS/AOM and randomized to receive either a control diet or GLN-enriched diet intermittently of the study. The disease activity index was evaluated weekly. On day 80 of the experiment, the entire colon and rectum were processed for histopathologic examination and further evaluation. Pro-inflammatory mediators and cytokines were measured by enzyme-linked immunosorbent assay, real-time-PCR and western blot analysis. Here, we show that after GLN-enriched diet, the colitis presented a statistical improvement and tumors burden decreased significantly. This was accompanied by lower activity of nuclear factor-κB (NF-κB), decreased expression of cyclooxygenase-2 and inducible nitric oxide synthase, lower expression of cytokines and chemokines as well as reduced proliferation and induced apoptosis in the colons of colitis-associated CRC mice. Our data demonstrate the protective/preventive effect of GLN in the progression of colitis-associated CRC, which was correlated with a dampening of inflammation and NF-κB activity and with a decrease of inflammatory protein overexpression.

NLRP6 inflammasome is a regulator of colonic microbial ecology and risk for colitis

PubMed Central

Elinav, Eran; Strowig, Till; Kau, Andrew L.; Henao-Mejia, Jorge; Thaiss, Christoph A.; Booth, Carmen J.; Peaper, David R.; Bertin, John; Eisenbarth, Stephanie C.; Gordon, Jeffrey I.; Flavell, Richard A.

2011-01-01

Inflammasomes are multi-protein complexes that function as sensors of endogenous or exogenous damage-associated molecular patterns. Here we show that deficiency of NLRP6 in mouse colonic epithelial cells results in reduced IL-18 levels and altered fecal microbiota characterized by expanded representation of the bacterial phyla Bacteroidetes (Prevotellaceae) and TM7. NLRP6 inflammasome-deficient mice were characterized by spontaneous intestinal hyperplasia, inflammatory cell recruitment, and exacerbation of chemical colitis induced by exposure to dextran sodium sulfate (DSS). Cross-fostering and cohousing experiments revealed that the colitogenic activity of this microbiota is transferable to neonatal or adult wild-type mice, leading to exacerbation of DSS colitis via induction of CCL5. Antibiotic treatment and electron microscopy studies further supported the role of Prevotellaceae as a key representative of this microbiota-associated phenotype. Altogether, perturbations in this inflammasome pathway, including NLRP6, ASC, caspase-1 and IL-18 may constitute a predisposing or initiating event in some cases of human IBD. PMID:21565393

Activation of Intestinal Human Pregnane X Receptor Protects against Azoxymethane/Dextran Sulfate Sodium–Induced Colon Cancer

PubMed Central

Cheng, Jie; Fang, Zhong-Ze; Nagaoka, Kenjiro; Okamoto, Minoru; Qu, Aijuan; Tanaka, Naoki; Kimura, Shioko

2014-01-01

The role of intestinal human pregnane X receptor (PXR) in colon cancer was determined through investigation of the chemopreventive role of rifaximin, a specific agonist of intestinal human PXR, toward azoxymethane (AOM)/dextran sulfate sodium (DSS)–induced colon cancer. Rifaximin treatment significantly decreased the number of colon tumors induced by AOM/DSS treatment in PXR-humanized mice, but not wild-type or Pxr-null mice. Additionally, rifaximin treatment markedly increased the survival rate of PXR-humanized mice, but not wild-type or Pxr-null mice. These data indicated a human PXR–dependent therapeutic chemoprevention of rifaximin toward AOM/DSS-induced colon cancer. Nuclear factor κ-light-chain-enhancer of activated B cells–mediated inflammatory signaling was upregulated in AOM/DSS-treated mice, and inhibited by rifaximin in PXR-humanized mice. Cell proliferation and apoptosis were also modulated by rifaximin treatment in the AOM/DSS model. In vitro cell-based assays further revealed that rifaximin regulated cell apoptosis and cell cycle in a human PXR-dependent manner. These results suggested that specific activation of intestinal human PXR exhibited a chemopreventive role toward AOM/DSS-induced colon cancer by mediating anti-inflammation, antiproliferation, and proapoptotic events. PMID:25277138

Improving an Atlantic Fisheries DSS using Sea Surface Salinity Data from NASA's Aquarius Mission

NASA Technical Reports Server (NTRS)

Guest, DeNeice

2007-01-01

This report assesses the capacity of incorporating NASA#s Aquarius SSS (sea surface salinity) data into the SMAST (School of Marine Science and Technology) DSS for Fisheries Science. This data will enhance the SMAST DSS by providing SSS over a large area. Aquarius is a focused satellite mission designed to measure global SSS. SSS mapping is limited because conventional in situ SSS sampling is too sparse to give a large-scale view of the salinity variability. Aquarius will resolve missing physical processes that link the water cycle, the climate, and the ocean. The SMAST Fisheries program provides a DSS for fisheries science. It collects fisheries and environmental data, integrates them into a suite of data assimilation ocean models, and provides hindcasts, nowcasts, and forecasts for fisheries research, fisheries management, and the fishery industry. Currently, SMAST is using SSS data from the National Oceanic and Atmospheric Administration#s National Data Buoy Center. The SMAST DSS would be enhanced with SSS data from the Aquarius mission.

Hydrogen sulfide from a NaHS source attenuates dextran sulfate sodium (DSS)-induced inflammation via inhibiting nuclear factor-κB

PubMed Central

Chen, Xi; Liu, Xi-shuang

2016-01-01

This study investigated the alleviating effects of hydrogen sulfide (H2S), derived from sodium hydrosulfide (NaHS), on inflammation induced by dextran sulfate sodium (DSS) in both in vivo and in vitro models. We found that NaHS injection markedly decreased rectal bleeding, diarrhea, and histological injury in DSS-challenged mice. NaHS (20 μmol/L) reversed DSS-induced inhibition in cell viability in Caco-2 cells and alleviated pro-inflammation cytokine expression in vivo and in vitro, indicating an anti-inflammatory function for H2S. It was also found that H2S may regulate cytokine expression by inhibiting the nuclear factor-κB (NF-κB) signaling pathway. In conclusion, our results demonstrated that H2S alleviated DSS-induced inflammation in vivo and in vitro and that the signal mechanism might be associated with the NF-κB signaling pathway. PMID:26984841

GREENER CHEMICAL PROCESS DESIGN ALTERNATIVES ARE REVEALED USING THE WASTE REDUCTION DECISION SUPPORT SYSTEM (WAR DSS)

EPA Science Inventory

The Waste Reduction Decision Support System (WAR DSS) is a Java-based software product providing comprehensive modeling of potential adverse environmental impacts (PEI) predicted to result from newly designed or redesigned chemical manufacturing processes. The purpose of this so...

Prevention of healthcare-associated infections: knowledge among dental students in seven Italian universities.

PubMed

Pasquarella, Cesira; Veronesi, Licia; Castiglia, Paolo; D'Alessandro, Daniela; Legnani, Pierpaolo; Minelli, Liliana; Montagna, Maria Teresa; Napoli, Christian; Righi, Elena; Strohmenger, Laura; Tesauro, Marina; Torre, Ida; Tanzi, Maria Luiza

2015-01-01

Lack of knowledge is the major reason for non-compliance with correct healthcare-associated infections (HAI) prevention procedures. The aim of this study was to evaluate knowledge of the Dental School (DSS) and Dental Hygiene (DHS) students with regard to the prevention of HAI, as basic knowledge for improving and harmonizing the educational content in the different Italian Universities. A cross-sectional study was carried out using an anonymous questionnaire that was completed by DSS (I, II, III, IV, and V year) in seven Universities and DHS (I, II, and III year) in three Universities. The questions dealt with three specific areas: healthcare-associated infections, standard precautions and hand hygiene. Factors associated with an unacceptable level of knowledge (score <17.5) were analyzed using a logistic regression model. A p value <0.05 was considered to be significant. Five hundred and four questionnaires were collected: 81.5% for DSS and 18.5% for DHS. Mean overall score (±DS) achieved by the total number of students was 18.2±2.93 on an overall perfect score of 25; 18.2±3.04 for DSS and 17.8±2.31 for DHS. Stratifying by area, the average score 2.7±1.07 (53%) for HAI, 10.3±1.61 (85.9%) for standard precautions, and 5.2±1.44 (64.8%) for hand hygiene was observed. A significantly different level of knowledge (p<0.001) between DSS and DHS was observed only for HAI (2.8±1.07 for DSS vs 2.1±0.96 for DHS). Significant differences among the academic years were found only for DSS concerning HAI and standard precautions. The logistic regression model showed that an age <23 years was a risk factor for lack of knowledge on HAI, but a protective factor for lack of knowledge about standard precautions and hand hygiene; attending DH degree course was associated with lack of knowledge on HAI. Although the overall score obtained both by DSS and DHS indicated an acceptable level of knowledge, lack of knowledge was highlighted, in particular, for hand hygiene. Therefore, it is necessary to implement and validate effective teaching models in undergraduate courses in order to provide the scientific basis and the theoretical and practical preparation for the prevention and control of HAI.

Overexpression of GATA-3 in T cells accelerates dextran sulfate sodium-induced colitis.

PubMed

Okamura, Midori; Yoh, Keigyou; Ojima, Masami; Morito, Naoki; Takahashi, Satoru

2014-01-01

Ulcerative colitis (UC) is an inflammatory bowel disease, and its pathogenesis includes genetic, environmental, and immunological factors, such as T helper cells and their secreted cytokines. T helper cells are classified as Th1, Th2, and Th17 cells. However, it is unclear which T helper cells are important in UC. Dextran sulfate sodium (DSS)-induced colitis is a commonly used model of UC. In this study, we induced DSS colitis in Th1 dominant (T-bet transgenic (Tg)) mice, Th2 dominant (GATA-3 Tg) mice, and Th17 dominant (RORγt Tg) mice to elucidate the roles of T helper cell in DSS colitis. The results showed that GATA-3 Tg mice developed the most severe DSS colitis compared with the other groups. GATA-3 Tg mice showed a significant decreased in weight from day 1 to day 7, and an increased high score for the disease activity index compared with the other groups. Furthermore, GATA-3 Tg mice developed many ulcers in the colon, and many neutrophils and macrophages were detected on day 4 after DSS treatment. Measurement of GATA-3-induced cytokines demonstrated that IL-13 was highly expressed in the colon from DSS-induced GATA-3 Tg mice. In conclusion, GATA-3 overexpression in T-cells and IL-13 might play important roles in the development of DSS colitis.

Decision support system development at the Upper Midwest Environmental Sciences Center

USGS Publications Warehouse

Fox, Timothy J.; Nelson, J. C.; Rohweder, Jason J.

2014-01-01

A Decision Support System (DSS) can be defined in many ways. The working definition used by the U.S. Geological Survey Upper Midwest Environmental Sciences Center (UMESC) is, “A spatially based computer application or data that assists a researcher or manager in making decisions.” This is quite a broad definition—and it needs to be, because the possibilities for types of DSSs are limited only by the user group and the developer’s imagination. There is no one DSS; the types of DSSs are as diverse as the problems they help solve. This diversity requires that DSSs be built in a variety of ways, using the most appropriate methods and tools for the individual application. The skills of potential DSS users vary widely as well, further necessitating multiple approaches to DSS development. Some small, highly trained user groups may want a powerful modeling tool with extensive functionality at the expense of ease of use. Other user groups less familiar with geographic information system (GIS) and spatial data may want an easy-to-use application for a nontechnical audience. UMESC has been developing DSSs for almost 20 years. Our DSS developers offer our partners a wide variety of technical skills and development options, ranging from the most simple Web page or small application to complex modeling application development.

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. Copyright © 2016 the American Physiological Society.

NASA Earth Science Research Results for Improved Regional Crop Yield Prediction

NASA Astrophysics Data System (ADS)

Mali, P.; O'Hara, C. G.; Shrestha, B.; Sinclair, T. R.; G de Goncalves, L. G.; Salado Navarro, L. R.

2007-12-01

National agencies such as USDA Foreign Agricultural Service (FAS), Production Estimation and Crop Assessment Division (PECAD) work specifically to analyze and generate timely crop yield estimates that help define national as well as global food policies. The USDA/FAS/PECAD utilizes a Decision Support System (DSS) called CADRE (Crop Condition and Data Retrieval Evaluation) mainly through an automated database management system that integrates various meteorological datasets, crop and soil models, and remote sensing data; providing significant contribution to the national and international crop production estimates. The "Sinclair" soybean growth model has been used inside CADRE DSS as one of the crop models. This project uses Sinclair model (a semi-mechanistic crop growth model) for its potential to be effectively used in a geo-processing environment with remote-sensing-based inputs. The main objective of this proposed work is to verify, validate and benchmark current and future NASA earth science research results for the benefit in the operational decision making process of the PECAD/CADRE DSS. For this purpose, the NASA South American Land Data Assimilation System (SALDAS) meteorological dataset is tested for its applicability as a surrogate meteorological input in the Sinclair model meteorological input requirements. Similarly, NASA sensor MODIS products is tested for its applicability in the improvement of the crop yield prediction through improving precision of planting date estimation, plant vigor and growth monitoring. The project also analyzes simulated Visible/Infrared Imager/Radiometer Suite (VIIRS, a future NASA sensor) vegetation product for its applicability in crop growth prediction to accelerate the process of transition of VIIRS research results for the operational use of USDA/FAS/PECAD DSS. The research results will help in providing improved decision making capacity to the USDA/FAS/PECAD DSS through improved vegetation growth monitoring from high spatial and temporal resolution remote sensing datasets; improved time-series meteorological inputs required for crop growth models; and regional prediction capability through geo-processing-based yield modeling.

The Tumor Suppressor Gene, RASSF1A, Is Essential for Protection against Inflammation -Induced Injury

PubMed Central

Fiteih, Yahya; Law, Jennifer; Volodko, Natalia; Mohamed, Anwar; El-Kadi, Ayman O. S.; Liu, Lei; Odenbach, Jeff; Thiesen, Aducio; Onyskiw, Christina; Ghazaleh, Haya Abu; Park, Jikyoung; Lee, Sean Bong; Yu, Victor C.; Fernandez-Patron, Carlos; Alexander, R. Todd; Wine, Eytan; Baksh, Shairaz

2013-01-01

Ras association domain family protein 1A (RASSF1A) is a tumor suppressor gene silenced in cancer. Here we report that RASSF1A is a novel regulator of intestinal inflammation as Rassf1a+/−, Rassf1a−/− and an intestinal epithelial cell specific knockout mouse (Rassf1a IEC-KO) rapidly became sick following dextran sulphate sodium (DSS) administration, a chemical inducer of colitis. Rassf1a knockout mice displayed clinical symptoms of inflammatory bowel disease including: increased intestinal permeability, enhanced cytokine/chemokine production, elevated nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFκB) activity, elevated colonic cell death and epithelial cell injury. Furthermore, epithelial restitution/repair was inhibited in DSS-treated Rassf1a−/− mice with reduction of several makers of proliferation including Yes associated protein (YAP)-driven proliferation. Surprisingly, tyrosine phosphorylation of YAP was detected which coincided with increased nuclear p73 association, Bax-driven epithelial cell death and p53 accumulation resulting in enhanced apoptosis and poor survival of DSS-treated Rassf1a knockout mice. We can inhibit these events and promote the survival of DSS-treated Rassf1a knockout mice with intraperitoneal injection of the c-Abl and c-Abl related protein tyrosine kinase inhibitor, imatinib/gleevec. However, p53 accumulation was not inhibited by imatinib/gleevec in the Rassf1a−/− background which revealed the importance of p53-dependent cell death during intestinal inflammation. These observations suggest that tyrosine phosphorylation of YAP (to drive p73 association and up-regulation of pro-apoptotic genes such as Bax) and accumulation of p53 are consequences of inflammation-induced injury in DSS-treated Rassf1a−/− mice. Mechanistically, we can detect robust associations of RASSF1A with membrane proximal Toll-like receptor (TLR) components to suggest that RASSF1A may function to interfere and restrict TLR-driven activation of NFκB. Failure to restrict NFκB resulted in the inflammation-induced DNA damage driven tyrosine phosphorylation of YAP, subsequent p53 accumulation and loss of intestinal epithelial homeostasis. PMID:24146755

Oral administration of red ginseng powder fermented with probiotic alleviates the severity of dextran-sulfate sodium-induced colitis in a mouse model.

PubMed

Jang, Sun-Hee; Park, Jisang; Kim, Sae-Hae; Choi, Kyung-Min; Ko, Eun-Sil; Cha, Jeong-Dan; Lee, Young-Ran; Jang, Hyonseok; Jang, Yong-Suk

2017-03-01

Red ginseng is a well-known alternative medicine with anti-inflammatory activity. It exerts pharmacological effects through the transformation of saponin into metabolites by intestinal microbiota. Given that intestinal microflora vary among individuals, the pharmacological effects of red ginseng likely vary among individuals. In order to produce homogeneously effective red ginseng, we prepared probiotic-fermented red ginseng and evaluated its activity using a dextran sulfate sodium (DSS)-induced colitis model in mice. Initial analysis of intestinal damage indicated that the administration of probiotic-fermented red ginseng significantly decreased the severity of colitis, compared with the control and the activity was higher than that induced by oral administration of ginseng powder or probiotics only. Subsequent analysis of the levels of serum IL-6 and TNF-α, inflammatory biomarkers that are increased at the initiation stage of colitis, were significantly decreased in probiotic-fermented red ginseng-treated groups in comparison to the control group. The levels of inflammatory cytokines and mRNAs for inflammatory factors in colorectal tissues were also significantly decreased in probiotic-fermented red ginseng-treated groups. Collectively, oral administration of probiotic-fermented red ginseng reduced the severity of colitis in a mouse model, suggesting that it can be used as a uniformly effective red ginseng product. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Impact of double-tiered subchondral support procedure with a polyaxial locking plate on the stability of distal radius fractures using fresh cadaveric forearms: Biomechanical and radiographic analyses.

PubMed

Tsutsui, Sadaaki; Kawasaki, Keikichi; Yamakoshi, Ken-Ichi; Uchiyama, Eiichi; Aoki, Mitsuhiro; Inagaki, Katsunori

2016-09-01

The present study compared the changes in biomechanical and radiographic properties under cyclic axial loadings between the 'double-tiered subchondral support' (DSS) group (wherein two rows of screws were used) and the 'non-DSS' (NDSS) group (wherein only one row of distal screws was used) using cadaveric forearm models of radius fractures fixed with a polyaxial locking plate. Fifteen fresh cadaveric forearms were surgically operated to generate an Arbeitsgemeinschaft für Osteosynthesefragen (AO) type 23-C2 fracture model with the fixation of polyaxial volar locking plates. The model specimens were randomized into two groups: DSS (n = 7) and NDSS (n = 8). Both the groups received 4 locking screws in the most distal row, as is usually applied, whereas the DSS group received 2 additional screws in the second row inserted at an inclination of about 15° to support the dorsal aspect of the dorsal subchondral bone. Cyclic axial compression test was performed (3000 cycles; 0-250 N; 60 mm/min) to measure absolute rigidity and displacement, after 1, 1000, 2000 and 3000 cycles, and values were normalized relative to cycle 1. These absolute and normalized values were compared between those two groups. Radiographic images were taken before and after the cyclic loading to measure changes in volar tilt (ΔVT) and radial inclination (ΔRI). The DSS group maintained significantly higher rigidity and lower displacement values than the NDSS group during the entire loading period. Radiographic analysis indicated that the ΔVT values of the DSS group were lower than those of the NDSS group. In contrast, the fixation design did not influence the impact of loading on the ΔRI values. Biomechanical and radiographic analyses demonstrated that two rows of distal locking screws in the DSS procedure conferred higher stability than one row of distal locking screws. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Use of the self-organising map network (SOMNet) as a decision support system for regional mental health planning.

PubMed

Chung, Younjin; Salvador-Carulla, Luis; Salinas-Pérez, José A; Uriarte-Uriarte, Jose J; Iruin-Sanz, Alvaro; García-Alonso, Carlos R

2018-04-25

Decision-making in mental health systems should be supported by the evidence-informed knowledge transfer of data. Since mental health systems are inherently complex, involving interactions between its structures, processes and outcomes, decision support systems (DSS) need to be developed using advanced computational methods and visual tools to allow full system analysis, whilst incorporating domain experts in the analysis process. In this study, we use a DSS model developed for interactive data mining and domain expert collaboration in the analysis of complex mental health systems to improve system knowledge and evidence-informed policy planning. We combine an interactive visual data mining approach, the self-organising map network (SOMNet), with an operational expert knowledge approach, expert-based collaborative analysis (EbCA), to develop a DSS model. The SOMNet was applied to the analysis of healthcare patterns and indicators of three different regional mental health systems in Spain, comprising 106 small catchment areas and providing healthcare for over 9 million inhabitants. Based on the EbCA, the domain experts in the development team guided and evaluated the analytical processes and results. Another group of 13 domain experts in mental health systems planning and research evaluated the model based on the analytical information of the SOMNet approach for processing information and discovering knowledge in a real-world context. Through the evaluation, the domain experts assessed the feasibility and technology readiness level (TRL) of the DSS model. The SOMNet, combined with the EbCA, effectively processed evidence-based information when analysing system outliers, explaining global and local patterns, and refining key performance indicators with their analytical interpretations. The evaluation results showed that the DSS model was feasible by the domain experts and reached level 7 of the TRL (system prototype demonstration in operational environment). This study supports the benefits of combining health systems engineering (SOMNet) and expert knowledge (EbCA) to analyse the complexity of health systems research. The use of the SOMNet approach contributes to the demonstration of DSS for mental health planning in practice.

Decision Support System for Reservoir Management and Operation in Africa

NASA Astrophysics Data System (ADS)

Navar, D. A.

2016-12-01

Africa is currently experiencing a surge in dam construction for flood control, water supply and hydropower production, but ineffective reservoir management has caused problems in the region, such as water shortages, flooding and loss of potential hydropower generation. Our research aims to remedy ineffective reservoir management by developing a novel Decision Support System(DSS) to equip water managers with a technical planning tool based on the state of the art in hydrological sciences. The DSS incorporates a climate forecast model, a hydraulic model of the watershed, and an optimization model to effectively plan for the operation of a system of cascade large-scale reservoirs for hydropower production, while treating water supply and flood control as constraints. Our team will use the newly constructed hydropower plants in the Omo Gibe basin of Ethiopia as the test case. Using the basic HIDROTERM software developed in Brazil, the General Algebraic Modeling System (GAMS) utilizes a combination of linear programing (LP) and non-linear programming (NLP) in conjunction with real time hydrologic and energy demand data to optimize the monthly and daily operations of the reservoir system. We compare the DSS model results with the current reservoir operating policy used by the water managers of that region. We also hope the DSS will eliminate the current dangers associated with the mismanagement of large scale water resources projects in Africa.

Successful Application of Adaptive Emotion Regulation Skills Predicts the Subsequent Reduction of Depressive Symptom Severity but neither the Reduction of Anxiety nor the Reduction of General Distress during the Treatment of Major Depressive Disorder

PubMed Central

Wirtz, Carolin M.; Radkovsky, Anna; Ebert, David D.; Berking, Matthias

2014-01-01

Objective Deficits in general emotion regulation (ER) skills have been linked to symptoms of depression and are thus considered a promising target in the treatment of Major depressive disorder (MDD). However, at this point, the extent to which such skills are relevant for coping with depression and whether they should instead be considered a transdiagnostic factor remain unclear. Therefore, the present study aimed to investigate whether successful ER skills application is associated with changes in depressive symptom severity (DSS), anxiety symptom severity (ASS), and general distress severity (GDS) over the course of treatment for MDD. Methods Successful ER skills application, DSS, ASS, and GDS were assessed four times during the first three weeks of treatment in 175 inpatients who met the criteria for MDD. We computed Pearson correlations to test whether successful ER skills application and the three indicators of psychopathology are cross-sectionally associated. We then performed latent growth curve modelling to test whether changes in successful ER skills application are negatively associated with a reduction of DSS, ASS, or GDS. Finally, we utilized latent change score models to examine whether successful ER skills application predicts subsequent reduction of DSS, ASS, or GDS. Results Successful ER skills application was cross-sectionally associated with lower levels of DSS, ASS, and GDS at all points of assessment. An increase in successful skills application during treatment was associated with a decrease in DSS and GDS but not ASS. Finally, successful ER skills application predicted changes in subsequent DSS but neither changes in ASS nor changes in GDS. Conclusions Although general ER skills might be relevant for a broad range of psychopathological symptoms, they might be particularly important for the maintenance and treatment of depressive symptoms. PMID:25330159

Decision support for sustainable forestry: enhancing the basic rational model.

Treesearch

H.R. Ekbia; K.M. Reynolds

2007-01-01

Decision-support systems (DSS) have been extensively used in the management of natural resources for nearly two decades. However, practical difficulties with the application of DSS in real-world situations have become increasingly apparent. Complexities of decisionmaking, encountered in the context of ecosystem management, are equally present in sustainable forestry....

Dietary Supplement Use Was Very High among Older Adults in the United States in 2011-2014.

PubMed

Gahche, Jaime J; Bailey, Regan L; Potischman, Nancy; Dwyer, Johanna T

2017-10-01

Background: Dietary supplements (DSs) have the potential to be both beneficial and harmful to health, especially in adults aged ≥60 y, and therefore it is important to monitor the patterns of their use. Objective: This study evaluated DS use by adults aged ≥60 y to characterize the use of DSs, determine the motivations for use, and examine the associations between the use of DSs and selected demographic, lifestyle, and health characteristics. Methods: Data from 3469 older adults aged ≥60 y from the 2011-2014 NHANES were analyzed. DSs used in the past 30 d were ascertained via an interviewer-administered questionnaire in participants' homes. The prevalence of overall DS use and specific types of DSs were estimated. The number of DSs reported and the frequency, duration, and motivation(s) for use were assessed. Logistic regression models were constructed to examine the association between DS use and selected characteristics. Results: Seventy percent of older adults in the United States reported using ≥1 DS in the past 30 d; 54% of users took 1 or 2 products, and 29% reported taking ≥4 products. The most frequently reported products were multivitamin or mineral (MVM) (39%), vitamin D only (26%), and omega-3 fatty acids (22%). Women used DSs almost twice as often as men [adjusted OR (aOR), 1.8; 95% CI: 1.5, 2.3). Those not reporting prescription medications were less likely to take a DS than those reporting ≥3 prescription medications (aOR, 0.4; 95% CI: 0.3, 0.6). The most frequently reported motivation for DS use was to improve overall health (41%). Conclusions: Use of DSs among older adults continues to be high in the United States, with 29% of users regularly taking ≥4 DSs, and there is a high concurrent usage of them with prescription medications. © 2017 American Society for Nutrition.

Interleukin-10 is differentially expressed in the small intestine and the colon experiencing chronic inflammation and ulcerative colitis induced by dextran sodium sulfate in young pigs.

PubMed

Lackeyram, D; Young, D; Kim, C J; Yang, C; Archbold, T L; Mine, Y; Fan, M Z

2017-03-31

Intestinal inflammation induced with dextran sodium sulfate (DSS) is used to study acute or chronic ulcerative colitis in animal models. Decreased gut tissue anti-inflammatory cytokine IL-10 concentration and mRNA abundance are associated with the development of chronic bowel inflammation. Twelve piglets of 3 days old were fitted with an intragastric catheter and randomly allocated into control and DSS groups by administrating either sterile saline or 1.25 g of DSS/kg body weight (BW) in saline per day, respectively, for 10 days. Growth rate and food conversion efficiency were reduced (p<0.05) in the DSS piglets compared with the control group. Quantitative histopathological grading of inflammation in the jejunum and colon collectively showed that the DSS treatment resulted in 12 fold greater (p<0.05) inflammation severity scoring in the colon than in the jejunum, indicative of chronic ulcerative colitis in the colon. Upper gut permeability endpoint was 27.4 fold higher (p<0.05) in the DSS group compared with the control group. The DSS group had higher concentrations and mRNA abundances (p<0.05) of TNF-alpha and IL-6 in the jejunal and colonic tissues compared with the control group. Colonic concentration and mRNA abundance of IL-10 were reduced (p<0.05), however, jejunal IL-10 mRNA abundance was increased (p<0.05) in the DSS group compared with the control group. In conclusion, administration of DSS at 1.25 g/kg BW for 10 days respectively induced acute inflammation in the jejunum and chronic inflammation and ulcerative colitis in the colon with substantially decreased colonic concentration and mRNA abundance of IL-10 in the young pigs, mimicking the IL-10 expression pattern in humans Associated with chronic bowel inflammation.

Building a Foreign Military Sales Construction Delivery Strategy Decision Support System

DTIC Science & Technology

1991-09-01

DSS, formulates it into a computer model and produces solutions using information and expert heuristics. Using the Expert Systeic Process to Build a DSS...computer model . There are five stages in the development of an expert system. They are: 1) Identify and characterize the important aspects of the problem...and Steven A. Hidreth. U.S. Security Assistance: The Political Process. Massachusetts: Heath and Company, 1985. 19. Guirguis , Amir A., Program

An Integrated Decision Support System with Hydrological Processes and Socio-economic Assessments

NASA Astrophysics Data System (ADS)

Yu, Yang; Disse, Markus; Yu, Ruide

2017-04-01

The debate over the effectiveness of Integrated Water Resources Management (IWRM) in practice has lasted for years. As the complexity and scope of IWRM increases, the difficulties of hydrological modeling is shifting from the model itself into the links with other cognate sciences, to understand the interactions among water, earth, ecosystem and humans. This work presents the design and development of a decision support system (DSS) that links the outputs of hydrological models with real-time decision making on social-economic assessments and land use changes. Discharge and glacier geometry changes were simulated with hydrological model WASA. Irrigation and ecological water were simulated by a new commercial software MIKE HYDRO. Groundwater was simulated by MODFLOW. All the outputs of theses hydrological models were integrated as inputs into the DSS in three types of links: regression equations, stationary data inputs, or dynamic data inputs into DSS as the models running parallel in the simulation periods. Within DSS, three types of logics were established: equations, conditional statements and fuzzy logics. The programming was realized in C++. The implementation of DSS takes place in the Tarim River Basin. With the mainstream of 1,321km and located in an arid area in northwest China, the Tarim River is China's longest inland river. The Tarim basin on the northern edge of the Taklamakan desert is an extremely arid region. In this region, agricultural water consumption and allocation management are crucial to address the conflicts among irrigation water users from upstream to downstream. Since 2011, the German Ministry of Science and Education BMBF established the Sino-German SuMaRiO project, for the sustainable management of river oases along the Tarim River. Project SuMaRiO focus on realizable management strategies, considering social, economic and ecological criteria. This will have positive effects for nearly 10 million inhabitants of different ethnic groups. DSS is the main outcome of SuMaRiO. The overall goal of the DSS is to integrate all crucial research results of SuMaRiO, also including stakeholder perspectives, into a model based decision support system, which allows a Sustainability Impact Assessment (SIA) within regional planning. This SIA will take into account the perspectives of all relevant actors in the problem field of land and water management in the Tarim River Basin, to understand ecosystem services (ESS) and integrating them into land and water management. Under scenario assumptions, possible actions and their impacts are estimated in a semi-quantitative way with the help of sustainable indicators, which includes climate indicators, socio-economic Indicators, management Indicators, and ESS Indicators. A user-friendly graphical user interface (GUI) was developed to assist the decision-makers and common users, with Chinese and English versions available at the moment.

Decision Support for Emergency Operations Centers

NASA Technical Reports Server (NTRS)

Harvey, Craig; Lawhead, Joel; Watts, Zack

2005-01-01

The Flood Disaster Mitigation Decision Support System (DSS) is a computerized information system that allows regional emergency-operations government officials to make decisions regarding the dispatch of resources in response to flooding. The DSS implements a real-time model of inundation utilizing recently acquired lidar elevation data as well as real-time data from flood gauges, and other instruments within and upstream of an area that is or could become flooded. The DSS information is updated as new data become available. The model generates realtime maps of flooded areas and predicts flood crests at specified locations. The inundation maps are overlaid with information on population densities, property values, hazardous materials, evacuation routes, official contact information, and other information needed for emergency response. The program maintains a database and a Web portal through which real-time data from instrumentation are gathered into the database. Also included in the database is a geographic information system, from which the program obtains the overlay data for areas of interest as needed. The portal makes some portions of the database accessible to the public. Access to other portions of the database is restricted to government officials according to various levels of authorization. The Flood Disaster Mitigation DSS has been integrated into a larger DSS named REACT (Real-time Emergency Action Coordination Tool), which also provides emergency operations managers with data for any type of impact area such as floods, fires, bomb

A Decision Support System for Mitigating Stream Temperature Impacts in the Sacramento River

NASA Astrophysics Data System (ADS)

Caldwell, R. J.; Zagona, E. A.; Rajagopalan, B.

2014-12-01

Increasing demands on the limited and variable water supply across the West can result in insufficient streamflow to sustain healthy fish habitat. We develop an integrated decision support system (DSS) for modeling and mitigating stream temperature impacts and demonstrate it on the Sacramento River system in California. Water management in the Sacramento River is a complex task with a diverse set of demands ranging from municipal supply to mitigation of fisheries impacts due to high water temperatures. Current operations utilize the temperature control device (TCD) structure at Shasta Dam to mitigate these high water temperatures downstream at designated compliance points. The TCD structure at Shasta Dam offers a rather unique opportunity to mitigate water temperature violations through adjustments to both release volume and temperature. In this study, we develop and evaluate a model-based DSS with four broad components that are coupled to produce the decision tool for stream temperature mitigation: (i) a suite of statistical models for modeling stream temperature attributes using hydrology and climate variables of critical importance to fish habitat; (ii) a reservoir thermal model for modeling the thermal structure and, consequently, the water release temperature, (iii) a stochastic weather generator to simulate weather sequences consistent with seasonal outlooks; and, (iv) a set of decision rules (i.e., 'rubric') for reservoir water releases in response to outputs from the above components. Multiple options for modifying releases at Shasta Dam were considered in the DSS, including mixing water from multiple elevations through the TCD and using different acceptable levels of risk. The DSS also incorporates forecast uncertainties and reservoir operating options to help mitigate stream temperature impacts for fish habitat, while efficiently using the reservoir water supply and cold pool storage. The use of these coupled tools in simulating impacts of future climate on stream temperature variability is also demonstrated. Results indicate that the DSS could substantially reduce the number of violations of thermal criteria, while ensuring maintenance of the cold pool storage throughout the summer.

Identifying the most appropriate age threshold for TNM stage grouping of well-differentiated thyroid cancer.

PubMed

Hendrickson-Rebizant, J; Sigvaldason, H; Nason, R W; Pathak, K A

2015-08-01

Age is integrated in most risk stratification systems for well-differentiated thyroid cancer (WDTC). The most appropriate age threshold for stage grouping of WDTC is debatable. The objective of this study was to evaluate the best age threshold for stage grouping by comparing multivariable models designed to evaluate the independent impact of various prognostic factors, including age based stage grouping, on the disease specific survival (DSS) of our population-based cohort. Data from population-based thyroid cancer cohort of 2125 consecutive WDTC, diagnosed during 1970-2010, with a median follow-up of 11.5 years, was used to calculate DSS using the Kaplan Meier method. Multivariable analysis with Cox proportional hazard model was used to assess independent impact of different prognostic factors on DSS. The Akaike information criterion (AIC), a measure of statistical model fit, was used to identify the most appropriate age threshold model. Delta AIC, Akaike weight, and evidence ratios were calculated to compare the relative strength of different models. The mean age of the patients was 47.3 years. DSS of the cohort was 95.6% and 92.8% at 10 and 20 years respectively. A threshold of 55 years, with the lowest AIC, was identified as the best model. Akaike weight indicated an 85% chance that this age threshold is the best among the compared models, and is 16.8 times more likely to be the best model as compared to a threshold of 45 years. The age threshold of 55 years was found to be the best for TNM stage grouping. Copyright © 2015 Elsevier Ltd. All rights reserved.

The development of an EDSS: Lessons learned and implications for DSS research

USGS Publications Warehouse

El-Gayar, O.; Deokar, A.; Michels, L.; Fosnight, G.

2011-01-01

The Solar and Wind Energy Resource Assessment (SWERA) project is focused on providing renewable energy (RE) planning resources to the public. Examples include wind, solar, and hydro assessments. SWERA DSS consists of three major components. First, SWERA 'Product Archive' provides for a discovery DSS upon which users can find and access renewable energy data and supporting models. Second, the 'Renewable Resource EXplorer' (RREX) component serves as a web-based, GIS analysis tool for viewing RE resource data available through the SWERA Product Archive. Third, the SWERA web service provides computational access to the data available in the SWERA spatial database through a location based query, and is also utilized in the RREX component. We provide a discussion of various design decisions used in the construction of this EDSS, followed by project experiences and implications for EDSS and broader DSS research. ?? 2011 IEEE.

GLP-1 nanomedicine alleviates gut inflammation

PubMed Central

Anbazhagan, Arivarasu N.; Thaqi, Mentor; Priyamvada, Shubha; Jayawardena, Dulari; Kumar, Anoop; Gujral, Tarunmeet; Chatterjee, Ishita; Mugarza, Edurne; Saksena, Seema; Onyuksel, Hayat; Dudeja, Pradeep K.

2017-01-01

The gut hormone, glucagon like peptide-1 (GLP-1) exerts anti-inflammatory effects. However, its clinical use is limited by its short half-life. Previously, we have shown that GLP-1 as a nanomedicine (GLP-1 in sterically stabilized phospholipid micelles, GLP-1-SSM) has increased in vivo stability. The current study was aimed at testing the efficacy of this GLP-1 nanomedicine in alleviating colonic inflammation and associated diarrhea in dextran sodium sulfate (DSS) induced mouse colitis model. Our results show that GLP-1-SSM treatment markedly alleviated the colitis phenotype by reducing the expression of pro-inflammatory cytokine IL-1β, increasing goblet cells and preserving intestinal epithelial architecture in colitis model. Further, GLP-1-SSM alleviated diarrhea (as assessed by luminal fluid) by increasing protein expression of intestinal chloride transporter DRA (down regulated in adenoma). Our results indicate thatGLP-1 nanomedicine may act as a novel therapeutic tool in alleviating gut inflammation and associated diarrhea in inflammatory bowel disease (IBD). PMID:27553076

Deoxycholic Acid-Mediated Sphingosine-1-Phosphate Receptor 2 Signaling Exacerbates DSS-Induced Colitis through Promoting Cathepsin B Release.

PubMed

Zhao, Shengnan; Gong, Zizhen; Du, Xixi; Tian, Chunyan; Wang, Lingyu; Zhou, Jiefei; Xu, Congfeng; Chen, Yingwei; Cai, Wei; Wu, Jin

2018-01-01

We recently have proved that excessive fecal DCA caused by high-fat diet may serve as an endogenous danger-associated molecular pattern to activate NLRP3 inflammasome and thus contributes to the development of inflammatory bowel disease (IBD). Moreover, the effect of DCA on inflammasome activation is mainly mediated through bile acid receptor sphingosine-1-phosphate receptor 2 (S1PR2); however, the intermediate process remains unclear. Here, we sought to explore the detailed molecular mechanism involved and examine the effect of S1PR2 blockage in a colitis mouse model. In this study, we found that DCA could dose dependently upregulate S1PR2 expression. Meanwhile, DCA-induced NLRP3 inflammasome activation is at least partially achieved through stimulating extracellular regulated protein kinases (ERK) signaling pathway downstream of S1PR2 followed by promoting of lysosomal cathepsin B release. DCA enema significantly aggravated DSS-induced colitis in mice and S1PR2 inhibitor as well as inflammasome inhibition by cathepsin B antagonist substantially reducing the mature IL-1 β production and alleviated colonic inflammation superimposed by DCA. Therefore, our findings suggest that S1PR2/ERK1/2/cathepsin B signaling plays a critical role in triggering inflammasome activation by DCA and S1PR2 may represent a new potential therapeutic target for the management of intestinal inflammation in individuals on a high-fat diet.

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 to increase the translation of animal and clinical studies. © 2016. Published by The Company of Biologists Ltd.

Does buccal cancer have worse prognosis than other oral cavity cancers?

PubMed

Camilon, P Ryan; Stokes, William A; Fuller, Colin W; Nguyen, Shaun A; Lentsch, Eric J

2014-06-01

To determine whether buccal squamous cell carcinoma has worse overall survival (OS) and disease-specific survival (DSS) than cancers in the rest of the oral cavity. Retrospective analysis of a large population database. We began with a Kaplan-Meier analysis of OS and DSS for buccal versus nonbuccal tumors with unmatched data, followed by an analysis of cases matched for race, age at diagnosis, stage at diagnosis, and treatment modality. This was supported by a univariate Cox regression comparing buccal cancer to nonbuccal cancer, followed by a multivariate Cox regression that included all significant variables studied. With unmatched data, buccal cancer had significantly lesser OS and DSS values than cancers in the rest of the oral cavity (P < .001). After case matching, the differences between OS and DSS for buccal cancer versus nonbuccal oral cancer were no longer significant. Univariate Cox regression models with respect to OS and DSS showed a significant difference between buccal cancer and nonbuccal cancer. However, with multivariate analysis, buccal hazard ratios for OS and DSS were not significant. With the largest series of buccal carcinoma to date, our study concludes that the OS and DSS of buccal cancer are similar to those of cancers in other oral cavity sites once age at diagnosis, tumor stage, treatment, and race are taken into consideration. The previously perceived poor prognosis of buccal carcinoma may be due to variations in tumor presentation, such as later stage and older patient age. 2b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

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

PubMed

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

2015-12-01

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

Atmospheric refraction correction for Ka-band blind pointing on the DSS-13 beam waveguide antenna

NASA Technical Reports Server (NTRS)

Perez-Borroto, I. M.; Alvarez, L. S.

1992-01-01

An analysis of the atmospheric refraction corrections at the DSS-13 34-m diameter beam waveguide (BWG) antenna for the period Jul. - Dec. 1990 is presented. The current Deep Space Network (DSN) atmospheric refraction model and its sensitivity with respect to sensor accuracy are reviewed. Refraction corrections based on actual atmospheric parameters are compared with the DSS-13 station default corrections for the six-month period. Average blind-pointing improvement during the worst month would have amounted to 5 mdeg at 10 deg elevation using actual surface weather values. This would have resulted in an average gain improvement of 1.1 dB.

Comparison of two models of inflammatory bowel disease in rats.

PubMed

Catana, Cristina Sorina; Magdas, Cristian; Tabaran, Flaviu Alexandru; Crăciun, Elena Cristina; Deak, Georgiana; Magdaş, Virginia Ana; Cozma, Vasile; Gherman, Călin Mircea; Berindan-Neagoe, Ioana; Dumitraşcu, Dan Lucian

2018-03-26

There is a need for experimental animal models for inflammatory bowel diseases (IBD), but no proposed model has been unanimously accepted. The aim of this study was to develop 2 affordable models of IBD in rats and to compare them. We produced IBD in rats using either dextran sodium sulfate (DSS) or 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The requirements for experimental models were: a predictable clinical course, histopathology and inflammation similar to human ulcerative colitis (UC) and Crohn's disease (CD). The effect of acute administration of DSS and TNBS on oxidative stress (as measured by the assessment of glutathione peroxidase - GPx) was verified. The activity of whole blood GPx was measured using a commercially available Randox kit (Crumlin, UK). The administration of DSS increased GPx activity compared to the control and TNBS-treated groups, but not to a statistically significant degree. Histological examination of the colonic mucosa following the administration of DSS showed multifocal erosions with minimal to mild inflammatory infiltrate, mainly by polymorphonuclear cells (PMN), lymphocytes and plasma cells. For TNBS-induced colitis, the histological changes manifested as multifocal areas of ulcerative colitis with mild to severe inflammatory infiltrate. Whole blood GPx values displayed a direct dependence on the chemical agent used. Our results show a correlation between histopathology, proinflammatory state and oxidative stress. The experimental DSSor TNBS-induced bowel inflammation used in this study corresponds to human IBD and is reproducible with characteristics indicative of acute inflammation in the case of the protocols mentioned.

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

Oral Delivery of Nanoparticles Loaded With Ginger Active Compound, 6-Shogaol, Attenuates Ulcerative Colitis and Promotes Wound Healing in a Murine Model of Ulcerative Colitis.

PubMed

Zhang, Mingzhen; Xu, Changlong; Liu, Dandan; Han, Moon Kwon; Wang, Lixin; Merlin, Didier

2018-01-24

Oral drug delivery is the most attractive pathway for ulcerative colitis [UC] therapy, since it has many advantages. However, this strategy has encountered many challenges, including the instability of drugs in the gastrointestinal tract [GT], low targeting of disease tissues, and severe adverse effects. Nanoparticles capable of colitis tissue-targeted delivery and site-specific drug release may offer a unique and therapeutically effective system that addresses these formidable challenges. We used a versatile single-step surface-functionalising technique to prepare PLGA/PLA-PEG-FA nanoparticles loaded with the ginger active compound, 6-shogaol [NPs-PEG-FA/6-shogaol]. The therapeutic efficacy of NPs-PEG-FA/6-shogaol was evaluated in the well-established mouse model of dextran sulphate sodium [DSS]-induced colitis. NPs-PEG-FA exhibited very good biocompatibility both in vitro and in vivo. Subsequent cellular uptake experiments demonstrated that NPs-PEG-FA could undergo efficient receptor-mediated uptake by colon-26 cells and activated Raw 264.7 macrophage cells. In vivo, oral administration of NPs-PEG-FA/6-shogaol encapsulated in a hydrogel system [chitosan/alginate] significantly alleviated colitis symptoms and accelerated colitis wound repair in DSS-treated mice by regulating the expression levels of pro-inflammatory [TNF-α, IL-6, IL-1β, and iNOS] and anti-inflammatory [Nrf-2 and HO-1] factors. Our study demonstrates a convenient, orally administered 6-shogaol drug delivery system that effectively targets colitis tissue, alleviates colitis symptoms, and accelerates colitis wound repair. This system may represent a promising therapeutic approach for treating inflammatory bowel disease [IBD]. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Fucoidan Extracts Ameliorate Acute Colitis

PubMed Central

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 a novel nutraceutical option for the management of IBD. PMID:26083103

TRPV2 in the development of experimental colitis.

PubMed

Issa, C M; Hambly, B D; Wang, Y; Maleki, S; Wang, W; Fei, J; Bao, S

2014-11-01

Colitis is still a significant disease challenge in humans, but its underlying mechanism remains to be fully elucidated. The transient receptor potential vanilloid (TRPV) ion channel plays an important pathological role in host immunity, as deficiency of TRPV compromises host defence in vivo and in vitro. Using a DSS-induced colitis mouse model, the function of TRPV2 in the development of colitis was investigated, utilizing TRPV2(-/-) and Wt mice. Less severe colitis was observed in TRPV2(-/-) , compared to that of Wt mice, at the clinical, histopathological and immunohistochemical levels. Compared to Wt mice, reduced severity of colitis in TRPV2(-/-) mice may be due to less intestinal inflammation via reduced recruitment of macrophages. The TRPV2 pathway contributes to the development of colitis. These data provide useful information for potential therapeutic intervention in colitis patients. © 2014 John Wiley & Sons Ltd.

Protective effects of Fc-fused PD-L1 on two different animal models of colitis.

PubMed

Song, Mi-Young; Hong, Chun-Pyo; Park, Seong Jeong; Kim, Jung-Hwan; Yang, Bo-Gie; Park, Yunji; Kim, Sae Won; Kim, Kwang Soon; Lee, Ji Yeung; Lee, Seung-Woo; Jang, Myoung Ho; Sung, Young-Chul

2015-02-01

Programmed death-ligand 1 (PD-L1) has been shown to negatively regulate immune responses via its interaction with PD-1 receptor. In this study, we investigated the effects of PD-L1-Fc treatment on intestinal inflammation using two murine models of inflammatory colitis induced by dextran sulfate sodium (DSS) and T-cell transfer. The anti-colitis effect of adenovirus expressing Fc-conjugated PD-L1 (Ad/PD-L1-Fc) and recombinant PD-L1-Fc protein was evaluated in DSS-treated wild-type and Rag-1 knockout (KO) mice. We examined differentiation of T-helper cells, frequency of innate immune cells, and cytokine production by dendritic cells (DCs) in the colon from DSS-treated mice after PD-L1-Fc administration. In Rag-1 KO mice reconstituted with CD4 CD45RB(high) T cells, we assessed the treatment effect of PD-L1-Fc protein on the development of colitis. Administration of Ad/PD-L1-Fc significantly ameliorated DSS-induced colitis, which was accompanied by diminished frequency of interleukin (IL)-17A-producing CD4 T cells and increased interferon-γ-producing CD4 T cells in the colon of DSS-fed mice. The anti-colitic effect of PD-L1-Fc treatment was also observed in DSS-treated Rag-1 KO mice, indicating lymphoid cell independency. PD-L1-Fc modulated cytokine production by colonic DCs and the effect was dependent on PD-1 expression. Furthermore, PD-L1-Fc protein could significantly reduce the severity of colitis in CD4 CD45RB(high) T-cell-transferred Rag-1 KO mice. Based on the protective effect of PD-L1-Fc against DSS-induced and T-cell-induced colitis, our results suggest that PD-1-mediated inhibitory signals have a crucial role in limiting the development of colonic inflammation. This implicates that PD-L1-Fc may provide a novel therapeutic approach to treat inflammatory bowel disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Attenuation of colonic inflammation by partial replacement of dietary linoleic acid with α-linolenic acid in a rat model of inflammatory bowel disease.

PubMed

Tyagi, Anupama; Kumar, Uday; Reddy, Suryam; Santosh, Vadakattu S; Mohammed, Saazida B; Ehtesham, Nasreen Z; Ibrahim, Ahamed

2012-11-14

Increasing prevalence of inflammatory bowel disease may be due to imbalance in the intake of n-6 and n-3 PUFA in the diet. This study investigates the impact of varying ratios of dietary linoleic acid (LA, 18 : 2n-6) to α-linolenic acid (ALA, 18 : 3n-3) on the inflammatory response in dextran sulphate sodium (DSS)-induced colitis. Weanling male Sprague-Dawley rats were divided into five groups: a non-colitic group with a LA:ALA ratio of 215 (CON-215), and colitic groups with LA:ALA ratios of 215 (DSS-215), 50 (DSS-50), 10 (DSS-10) and 2 (DSS-2). Blends of groundnut, palmolein and linseed oils were used to provide varying LA:ALA ratios. All the rats were fed the respective experimental isoenergetic diets containing 10 % fat for 90 d and DSS was administered during the last 11 d. Colonic inflammation was evaluated by clinical, biochemical and histological parameters. The results showed attenuation of colitis in the DSS-2 group as evidenced by significant reductions in disease activity index, mucosal myeloperoxidase activity (P < 0·05), alkaline phosphatase activity (P < 0·01) and increase in colon length (P < 0·01) compared to the groups fed with higher ratios (DSS-215). This was accompanied by significant reductions in mucosal proinflammatory cytokines TNF-α (P < 0·01) and IL-1β (P < 0·01) and improvement in the histological score. Further, ALA supplementation increased long-chain (LC) n-3 PUFA and decreased LC n-6 PUFA in colon structural lipids. These data suggest that substitution of one-third of LA with ALA (LA:ALA ratio 2) mitigates experimental colitis by down-regulating proinflammatory mediators.

Brown rice and retrograded brown rice alleviate inflammatory response in dextran sulfate sodium (DSS)-induced colitis mice.

PubMed

Praengam, Kemika; Sahasakul, Yuraporn; Kupradinun, Piengchai; Sakarin, Siriwan; Sanitchua, Wanwisa; Rungsipipat, Anudep; Rattanapinyopituk, Kasem; Angkasekwinai, Pornpimon; Changsri, Khaimuk; Mhuantong, Wuttichai; Tangphatsornruang, Sithichoke; Tuntipopipat, Siriporn

2017-12-13

The present study was aimed to investigate the impacts of brown rice (BR) and retrograded brown rice (R-BR) consumption on colonic health and gut microbiota in dextran sulfate sodium (DSS) induced colitis mice. Thirty two female C57Bl/6Mlac mice were fed with modified AIN 93G diets by replacing cornstarch in the original composition with white rice (WR), BR and R-BR powder. The mice were divided into 4 groups and fed with the following experimental diets for 4 weeks: (1) negative control (WR: diet with WR), (2) positive control (DSS_WR: DSS and diet with WR), (3) DSS_BR: DSS and diet with BR, and (4) DSS_R-BR: DSS and diet with R-BR. BR and R-BR had a greater content of fat, dietary fiber, GABA, γ-oryzanol, γ-tocotrienol, ferulic acid and p-coumaric acid than WR (p < 0.05). No significant difference in the level of these bioactive compounds was noted between BR and R-BR. Nevertheless, R-BR had a 1.8 fold resistant starch (RS) content of BR (p < 0.05). The DSS_BR and DSS_R-BR groups showed a lower ratio of colonic weight to length, and a lower content of iNOS, COX-2, MPO, IL-6 and INF-γ in colonic homogenates than the DSS_WR group. However, the DSS treated mice fed with the R-BR diet had significantly milder histopathological inflammatory injury and lower colonic iNOS expression than the DSS_BR and DSS_WR groups. The percentage of mesenteric regulatory T cells significantly increased in the DSS_R-BR group compared to that in the DSS_WR group. The DSS treated mice fed with the R-BR diet showed a significant increase in cecal bacterial diversity and abundance of genera Prevotella, Ruminococcus, Dorea, Coprococcus and Dehalobacterium but a significant decrease in pathogenic bacteria including Bacteroides and Enterococcus compared to the DSS_WR group. Thus, the present data indicate that BR and R-BR ameliorate colonic inflammation in experimental colitis induced by DSS in mice by suppressing inflammatory mediators and modulating regulatory T cell responses as well as bacterial diversity in the cecum.

Factors of accepting pain management decision support systems by nurse anesthetists

PubMed Central

2013-01-01

Background Pain management is a critical but complex issue for the relief of acute pain, particularly for postoperative pain and severe pain in cancer patients. It also plays important roles in promoting quality of care. The introduction of pain management decision support systems (PM-DSS) is considered a potential solution for addressing the complex problems encountered in pain management. This study aims to investigate factors affecting acceptance of PM-DSS from a nurse anesthetist perspective. Methods A questionnaire survey was conducted to collect data from nurse anesthetists in a case hospital. A total of 113 questionnaires were distributed, and 101 complete copies were returned, indicating a valid response rate of 89.3%. Collected data were analyzed by structure equation modeling using the partial least square tool. Results The results show that perceived information quality (γ=.451, p<.001), computer self-efficacy (γ=.315, p<.01), and organizational structure (γ=.210, p<.05), both significantly impact nurse anesthetists’ perceived usefulness of PM-DSS. Information quality (γ=.267, p<.05) significantly impacts nurse anesthetists’ perceptions of PM-DSS ease of use. Furthermore, both perceived ease of use (β=.436, p<.001, R2=.487) and perceived usefulness (β=.443, p<.001, R2=.646) significantly affected nurse anesthetists’ PM-DSS acceptance (R2=.640). Thus, the critical role of information quality in the development of clinical decision support system is demonstrated. Conclusions The findings of this study enable hospital managers to understand the important considerations for nurse anesthetists in accepting PM-DSS, particularly for the issues related to the improvement of information quality, perceived usefulness and perceived ease of use of the system. In addition, the results also provide useful suggestions for designers and implementers of PM-DSS in improving system development. PMID:23360305

Self-Organized Patterns in Gas-Discharge: Particle-Like Behaviour and Dissipative Solitons

NASA Astrophysics Data System (ADS)

Purwins, H.-G.

2008-03-01

The understanding of self-organise patterns in spatially extended nonlinear dissipative systems (SOPs) is one of the most challenging subjects in modern natural sciences. In the last 20 years it turned out that research in the field of low temperature gas-discharge can help to obtain insight into important aspect of SOPs. At the same time, due to the practical relevance of plasma systems one might expect interesting applications. In the present paper the focus is on self-organised filamentary patterns in planar dc and ac systems with high ohmic and dielectric barrier, respectively. - In the discharge plane of these systems filaments show up as spots which are also referred to as dissipative solitons (DSs). In many respect experimentally detected DSs exhibit particle-like behaviour. Among other things, isolated stationary or travelling DSs, stationary, travelling or rotating "molecules" and various kinds of many-body systems have been observed. Also scattering, generation and annihilation of DSs are frequent phenomena. - At least some of these patterns can be described quantitatively in terms of a drift diffusion model. It is also demonstrated that a simple reaction diffusion model allows for an intuitive understanding of many of the observed phenomena. At the same time this model is the basis for a theoretical foundation of the particle picture and the experimentally observed universal behaviour of SOPs. - Finally some hypothetical applications are discussed.

Circulating DNA and its methylation level in inflammatory bowel disease and related colon cancer.

PubMed

Bai, Xuming; Zhu, Yaqun; Pu, Wangyang; Xiao, Li; Li, Kai; Xing, Chungen; Jin, Yong

2015-01-01

Both of chronic inflammation and abnormal immune in inflammatory bowel disease can induce colon cancer. Previous research showed that cell apoptosis and necrosis become the main source of circulating DNA in the peripheral blood during tumorigenesis that reduced along with methylation degree. However, its role in the process of colitis transforming to colon cancer is not clarified. Drinking 3% DSS was used to establish colitis model, while 3% dextran sodium sulfate (DSS) combined with azo oxidation methane (AOM) intraperitoneal injection was applied to establish colitis related colon cancer model. Circulating DNA and its methylation level in peripheral blood were tested. Morphology observation, HE staining, and p53 and β-catenin expression detection confirmed that drinking 3% DSS and 3% DSS combined with AOM intraperitoneal injection can successfully establish colitis and colitis associated colorectal cancer models. Circulating DNA level in colitis and colon cancer mice increased by gradient compared with control, while significant difference was observed between each other. Circulating DNA methylation level decreased obviously in colitis and colon cancer, and significant difference was observed between each other. Abnormal protein expression, circulating DNA and its methylation level in ulcerative colitis associated colorectal tissues change in gradient, suggesting that circulating DNA and its methylation level can be treated as new markers for colitis cancer transformation that has certain significance to explore the mechanism of human ulcerative colitis canceration.

Insulin resistance and cognitive test performance in elderly adults: National health and nutrition examination survey (NHANES).

PubMed

Sherzai, Ayesha Z; Shaheen, Magda; Yu, Jeffrey J; Talbot, Konrad; Sherzai, Dean

2018-05-15

To examine the relationship between homeostatic model of insulin resistance (HOMA-IR) and cognitive test performance among population≥60years in a national database. Higher insulin resistance is associated with lower cognitive test performance score in the population≥60years. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2001-2002. Cognitive test performance was measured by the Digit Symbol Substitution (DSS) exercise score. The main independent variable was the homeostasis model assessment of insulin resistance (HOMA-IR). We used bivariate analysis and generalized linear model adjusting for age, gender, race, education, body mass index, and systolic and diastolic blood pressures; total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride levels; and physical activity, diabetes mellitus, stroke, and congestive heart failure. STATA 14 was used to analyze the data taking into consideration the design, strata and weight. Of the 1028 participants, 44% were male and 85% were white. The mean age was 70.0±0.28 (SE) years. Their average HOMA-IR was 3.6±0.14 and they had a mean of 49.2±0.8 correct DSS score in the cognitive test. Adjusting for the confounding variables, HOMA-IR was associated with decline in DSS score (B=-0.30, 95% confidence interval=-0.54 and -0.05, p=0.01). The model explained 44% of the variability of the DSS score (R 2 =0.44). Significant predictors of decline in DSS score were age, gender, race, and education (p=0.01). Insulin resistance as measured by HOMA-IR was independently associated with lower cognitive test performance score among elderly participants aged ≥60years. Longitudinal studies are needed to test the mechanism and the causal relationship. Copyright © 2017. Published by Elsevier B.V.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klein, Steven Karl; Day, Christy M.; Determan, John C.

LANL has developed a process to generate a progressive family of system models for a fissile solution system. This family includes a dynamic system simulation comprised of coupled nonlinear differential equations describing the time evolution of the system. Neutron kinetics, radiolytic gas generation and transport, and core thermal hydraulics are included in the DSS. Extensions to explicit operation of cooling loops and radiolytic gas handling are embedded in these systems as is a stability model. The DSS may then be converted to an implementation in Visual Studio to provide a design team the ability to rapidly estimate system performance impactsmore » from a variety of design decisions. This provides a method to assist in optimization of the system design. Once design has been generated in some detail the C++ version of the system model may then be implemented in a LabVIEW user interface to evaluate operator controls and instrumentation and operator recognition and response to off-normal events. Taken as a set of system models the DSS, Visual Studio, and LabVIEW progression provides a comprehensive set of design support tools.« less

Do pre-existing diabetes social support or depressive symptoms influence the effectiveness of a diabetes management intervention?

PubMed

Rosland, Ann-Marie; Kieffer, Edith; Spencer, Michael; Sinco, Brandy; Palmisano, Gloria; Valerio, Melissa; Nicklett, Emily; Heisler, Michele

2015-11-01

Examine influences of diabetes-specific social support (D-SS) and depressive symptoms on glycemic control over time, among adults randomized to a diabetes self-management education and support (DSME/S) intervention or usual care. Data were from 108 African-American and Latino participants in a 6-month intervention trial. Multivariable linear regression models assessed associations between baseline D-SS from family and friends and depressive symptoms with changes in HbA1c. We then examined whether baseline D-SS or depression moderated intervention-associated effects on HbA1c. Higher baseline D-SS was associated with larger improvements in HbA1c (adjusted ΔHbA1c -0.39% for each +1-point D-SS, p=0.02), independent of intervention-associated HbA1c decreases. Baseline depressive symptoms had no significant association with subsequent HbA1c change. Neither D-SS nor depression moderated intervention-associated effects on HbA1c. Diabetes self-management education and support programs have potential to improve glycemic control for participants starting with varying levels of social support and depressive symptoms. Participants starting with more support for diabetes management from family and friends improved HbA1c significantly more over 6 months than those with less support, independent of additional significant DSME/S intervention-associated HbA1c improvements. Social support from family and friends may improve glycemic control in ways additive to DSME/S. Published by Elsevier Ireland Ltd.

Diphenyl diselenide attenuates oxidative stress and inflammatory parameters in ulcerative colitis: A comparison with ebselen.

PubMed

Petronilho, Fabricia; Michels, Monique; Danielski, Lucinéia G; Goldim, Mariana Pereira; Florentino, Drielly; Vieira, Andriele; Mendonça, Mariana G; Tournier, Moema; Piacentini, Bárbara; Giustina, Amanda Della; Leffa, Daniela D; Pereira, Gregório W; Pereira, Volnei D; Rocha, João Batista Teixeira Da

2016-09-01

The aim of this study was to evaluate the effects of diphenyl diselenide (PhSe)2 and ebselen (EB) in ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in rats. The effects of (PhSe)2 and EB in rats submitted to DSS-induced colitis were determined by measurement of oxidative stress parameters, inflammatory response and bowel histopathological alterations. Animals developed moderate to severe neutrophil infiltration in histopathology assay in DSS rats and (PhSe)2 improved this response. Moreover, the treatment with (PhSe)2 decreased the oxidative damage in lipids and proteins, as well as reversed the superoxide dismutase (SOD) and catalase (CAT) levels in rats treated with DSS. EB was able only to reverse damage in lipids and the low levels of SOD in this animal model. The organoselenium compounds tested demonstrated an anti-inflammatory and antioxidant activity reducing the colon damage, being (PhSe)2 more effective than EB. Copyright © 2016 Elsevier GmbH. All rights reserved.

A genetic and pathologic study of a DENV2 clinical isolate capable of inducing encephalitis and hematological disturbances in immunocompetent mice.

PubMed

Amorim, Jaime Henrique; Pereira Bizerra, Raíza Sales; dos Santos Alves, Rúbens Prince; Sbrogio-Almeida, Maria Elisabete; Levi, José Eduardo; Capurro, Margareth Lara; de Souza Ferreira, Luís Carlos

2012-01-01

Dengue virus (DENV) is the causative agent of dengue fever (DF), a mosquito-borne illness endemic to tropical and subtropical regions. There is currently no effective drug or vaccine formulation for the prevention of DF and its more severe forms, i.e., dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). There are two generally available experimental models for the study of DENV pathogenicity as well as the evaluation of potential vaccine candidates. The first model consists of non-human primates, which do not develop symptoms but rather a transient viremia. Second, mouse-adapted virus strains or immunocompromised mouse lineages are utilized, which display some of the pathological features of the infection observed in humans but may not be relevant to the results with regard to the wild-type original virus strains or mouse lineages. In this study, we describe a genetic and pathological study of a DENV2 clinical isolate, named JHA1, which is naturally capable of infecting and killing Balb/c mice and reproduces some of the symptoms observed in DENV-infected subjects. Sequence analyses demonstrated that the JHA1 isolate belongs to the American genotype group and carries genetic markers previously associated with neurovirulence in mouse-adapted virus strains. The JHA1 strain was lethal to immunocompetent mice following intracranial (i.c.) inoculation with a LD(50) of approximately 50 PFU. Mice infected with the JHA1 strain lost weight and exhibited general tissue damage and hematological disturbances, with similarity to those symptoms observed in infected humans. In addition, it was demonstrated that the JHA1 strain shares immunological determinants with the DENV2 NGC reference strain, as evaluated by cross-reactivity of anti-envelope glycoprotein (domain III) antibodies. The present results indicate that the JHA1 isolate may be a useful tool in the study of DENV pathogenicity and will help in the evaluation of anti-DENV vaccine formulations as well as potential therapeutic approaches.

New insights on the modulatory roles of metformin or alpha-lipoic acid versus their combination in dextran sulfate sodium-induced chronic colitis in rats.

PubMed

Samman, Fatma S; Elaidy, Samah M; Essawy, Soha S; Hassan, Mohammad S

2017-11-24

Dextran sulfate sodium (DSS)-induced colitis is the most widely used model that resembles ulcerative colitis (UC) in human with challenging chronic mechanistic oxidative stress-inflammatory/immunological cascades. In models of acute colitis, reduction of oxidative stress and inflammatory burdens beside manipulation of many transcriptional factors were achieved by metformin or alpha-lipoic acid (α-LA). Currently, in vivo DSS-induced chronic colitis was conducted and the possible therapeutic roles of metformin and/or α-LA were explored. Chronic UC was induced by adding 5% DSS orally in drinking water for 7 days followed by 3% DSS in drinking water for 14 days in adult male albino Wistar rats. Intraperitoneal administration of α-LA (25 mg/kg, twice/day) and/or metformin (100 mg/kg/day) were set at day 7 of DSS administration and continued for 14 days. Body weights, survival rates, disease activity index (DAI), colonic oxidative stress markers, tumor necrosis factor (TNF)-α levels, colonic nuclear factor-kappa-B (NF-κB) immunohistochemical expression, and the colonic histopathological changes were observed. Metformin or/and α-LA attenuated the severity of the DSS-induced colitis through improving the reductions in body weights, the DAI, the colonic oxidative stress markers, TNF-α, and NF-κB levels, and the morphological mucosal damage scores. Significant synergetic therapeutic effects were observed with combined therapeutic regimens. Therapeutically, metformin and α-LA could be administered in chronic colitis. The combination of currently used pharmaceutics with natural and synthetic potent antioxidant compounds will become a therapeutic strategy of choice for UC to improve the quality of life if sufficient clinical trials are available. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

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 T 2 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. PMID:23894361

Use of the Decision Support System for VA cost-effectiveness research.

PubMed

Barnett, P G; Rodgers, J H

1999-04-01

The Department of Veterans Affairs is adopting the Decision Support System (DSS), computer software and databases which include a cost-accounting system which determines the cost of health care products and patient encounters. A system for providing cost data for cost-effectiveness analysis should be provide valid, detailed, and comprehensive data that can be aggregated. The design of DSS is described and compared with those criteria. Utilization data from DSS was compared with other VA utilization data. Aggregate DSS cost data from 35 medical centers was compared with relative resource weights developed for the Medicare program. Data on hospital stays at 3 facilities found that 3.7% of the stays in DSS were not in the VA discharge database, whereas 7.6% of the stays in the discharge data were not in DSS. DSS reported between 68.8% and 97.1% of the outpatient encounters reported by six facilities in the ambulatory care data base. Relative weights for each Diagnosis Related Group based on DSS data from 35 VA facilities correlated with Medicare weights (correlation coefficient of .853). DSS will be useful for research if certain problems are overcome. It is difficult to distinguish long-term from acute hospital care. VA does not have a complete database of all inpatient procedures, so DSS has not assigned them a specific cost. The authority to access encounter-level DSS data needs to be centralized. Researchers can provide the feedback needed to improve DSS cost estimates. A comprehensive encounter-level extract would facilitate use of DSS for research.

A simple model for DSS-14 outage times

NASA Technical Reports Server (NTRS)

Rumsey, H. C.; Stevens, R.; Posner, E. C.

1989-01-01

A model is proposed to describe DSS-14 outage times. Discrepancy Reporting System outage data for the period from January 1986 through September 1988 are used to estimate the parameters of the model. The model provides a probability distribution for the duration of outages, which agrees well with observed data. The model depends only on a small number of parameters, and has some heuristic justification. This shows that the Discrepancy Reporting System in the Deep Space Network (DSN) can be used to estimate the probability of extended outages in spite of the discrepancy reports ending when the pass ends. The probability of an outage extending beyond the end of a pass is estimated as around 5 percent.

Ghrelin administration suppresses inflammation-associated colorectal carcinogenesis in mice

PubMed Central

Kawaguchi, Makiko; Kanemaru, Ai; Fukushima, Tsuyoshi; Yamamoto, Koji; Tanaka, Hiroyuki; Haruyama, Yukihiro; Itoh, Hiroshi; Matsumoto, Nobuhiro; Kangawa, Kenji; Nakazato, Masamitsu; Kataoka, Hiroaki

2015-01-01

Ghrelin is a 28-amino-acid peptide that stimulates the release of pituitary growth hormone. Because of its orexigenic effects, ghrelin is being developed as a therapeutic option for postoperative support and treatment of anorexia-cachexia syndrome of cancer patients. However, ghrelin has a multiplicity of physiological functions, and it also affects cell proliferation. Therefore, the effects of ghrelin administration on carcinogenesis and cancer progression in patients susceptible to cancer should be clarified. In this study, we examined the effects of ghrelin on cancer promotion in vivo using murine intestinal carcinogenesis models. Intestinal tumorigenesis was examined to determine the effects of either exogenous ghrelin administration or ghrelin deficiency following deletion of the Ghrl gene. Two murine intestinal tumorigenesis models were used. The first was the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced inflammation-associated colon carcinogenesis model and the second was the ApcMin/+ genetic cancer susceptibility model. In AOM/DSS-treated mice, administration of ghrelin significantly suppressed tumor formation in the colon. In contrast, ghrelin administration did not affect the number of intestinal tumors formed in ApcMin/+ mice. The absence of endogenous ghrelin did not affect the incidence of intestinal tumors in either AOM/DSS-treated mice or ApcMin/+ mice, though tumor size tended to be larger in Ghrl−/− colons in the AOM/DSS model. No tumor-promoting effect was observed by ghrelin administration in either tumorigenesis model. In summary, this study provides in vivo experimental evidence for the usefulness of ghrelin administration in the chemoprevention of inflammation-associated colorectal carcinogenesis and may suggest its safety in patients under colitis-associated cancer susceptibility conditions. PMID:26094822

User manuals for the Delaware River Basin Water Availability Tool for Environmental Resources (DRB–WATER) and associated WATER application utilities

USGS Publications Warehouse

Williamson, Tanja N.; Lant, Jeremiah G.

2015-11-18

The Water Availability Tool for Environmental Resources (WATER) is a decision support system (DSS) for the nontidal part of the Delaware River Basin (DRB) that provides a consistent and objective method of simulating streamflow under historical, forecasted, and managed conditions. WATER integrates geospatial sampling of landscape characteristics, including topographic and soil properties, with a regionally calibrated hillslope-hydrology model, an impervious-surface model, and hydroclimatic models that have been parameterized using three hydrologic response units—forested, agricultural, and developed land cover. It is this integration that enables the regional hydrologic-modeling approach used in WATER without requiring site-specific optimization or those stationary conditions inferred when using a statistical model. The DSS provides a “historical” database, ideal for simulating streamflow for 2001–11, in addition to land-cover forecasts that focus on 2030 and 2060. The WATER Application Utilities are provided with the DSS and apply change factors for precipitation, temperature, and potential evapotranspiration to a 1981–2011 climatic record provided with the DSS. These change factors were derived from a suite of general circulation models (GCMs) and representative concentration pathway (RCP) emission scenarios. These change factors are based on 25-year monthly averages (normals) that are centere on 2030 and 2060. The WATER Application Utilities also can be used to apply a 2010 snapshot of water use for the DRB; a factorial approach enables scenario testing of increased or decreased water use for each simulation. Finally, the WATER Application Utilities can be used to reformat streamflow time series for input to statistical or reservoir management software. 

Identification of Two Additional Susceptibility Loci for Inflammatory Bowel Disease in a Chinese Population.

PubMed

Lan, Xiucai; Lan, Xiuhua; Chang, Ying; Zhang, Xiaomin; Liu, Jing; Vikash, Vikash; Wang, Wei; Huang, Meifang; Wang, Xiaobing; Zhou, Feng; Chen, Liping; Zhao, Qiu

2017-01-01

To investigate the associations between the rs1250569 (zinc finger MIZ-type containing 1, ZMIZ1), rs1042522 (tumour protein p53, TP53), and rs10114470 (tumour necrosis factor-like cytokine 1A, TL1A) polymorphisms and the development of inflammatory bowel disease (IBD) in a Chinese (Han) population. We analysed the expression of genes that predispose patients to Crohn's disease (CD) and ulcerative colitis (UC). A total of 381 IBD patients and 517 healthy controls were recruited into our study. Polymorphisms at the three loci were genotyped using polymerase chain reaction-ligation detection reactions (PCR-LDR). Genotype-phenotype correlations were analysed. Blood and gut samples were obtained and analysed using quantitative real-time PCR (qRT-PCR), western blot analysis, and immunohistochemistry to investigate the mRNA and protein levels and in situ expression of genes found to predispose patients to IBD. Furthermore, the expression of susceptible genes was further verified using a mouse dextran sulphate sodium (DSS)-induced acute colitis model. No significant association was detected between rs1250569 and rs1042522 genotypes and CD or UC susceptibility. However, the frequency of allele A of rs1250569 was much higher in CD patients than that in healthy controls (55.03% vs. 48.48%, respectively; p = 0.044). The mutation rates at rs10114470 were dramatically lower at both the genotype and allele level in patients than those in healthy controls (p = 0.002 at both the genotype and allele level). Additionally, increased ZMIZ1 and TL1A levels were detected in intestinal samples obtained from both IBD patients and DSS-treated mice. rs1250569 (ZMIZ1) and rs10114470 (TL1A) are two novel loci that indicate susceptibility to IBD in Han-Chinese patients. Consistent with previous studies, TL1A expression levels were higher in Chinese Han IBD patients and DSS-treated mice. Most importantly, we found that ZMIZ1 expression was markedly higher in both IBD patients and mice with experimentally induced colitis, suggesting that ZMIZ1 plays important roles in the pathogenesis of IBD. © 2017 The Author(s)Published by S. Karger AG, Basel.

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

MicroRNA-155 promotes the pathogenesis of experimental colitis by repressing SHIP-1 expression

PubMed Central

Lu, Zhan-Jun; Wu, Jian-Jiong; Jiang, Wei-Liang; Xiao, Jun-Hua; Tao, Kai-Zhong; Ma, Lei; Zheng, Ping; Wan, Rong; Wang, Xing-Peng

2017-01-01

AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3’-UTR. MiR-155 mimics, negative controls and SHIP-1 expression/knockdown vectors were established and then utilized in gain- and loss-of-function studies performed in raw264.7 cells and primary bone marrow-derived macrophages (BMDMs). Thereafter, dextran sulfate sodium (DSS)-induced colitis mouse model with or without antagomiR-155 treatment was established, and the levels of miR-155 and SHIP-1, as well as the pro-inflammatory capabilities, were measured by western blot, quantitative polymerase chain reaction, and immunohistochemistry. RESULTS MiR-155 directly bound to the 3’-UTR of SHIP-1 mRNA and induced a significant decrease in SHIP-1 expression in both raw264.7 cells and primary BMDMs. MiR-155 markedly promoted cell proliferation and pro-inflammatory secretions including IL-6, TNF-α, IL-1β, and IFN-γ, whereas these effects could be reversed by the restoration of SHIP-1 expression. In vivo studies showed that antagomiR-155 administration could alleviate DSS-induced intestinal inflammation in Balb/c mice. Moreover, significantly increased SHIP-1 expression, as well as decreased Akt activation and inflammatory response, were observed in the antagomiR-155-treated mice. CONCLUSION MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy. PMID:28246471

Seismic and Infrasound Location

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arrowsmith, Stephen J.; Begnaud, Michael L.

2014-03-19

This presentation includes slides on Signal Propagation Through the Earth/Atmosphere Varies at Different Scales; 3D Seismic Models: RSTT; Ray Coverage (Pn); Source-Specific Station Corrections (SSSCs); RSTT Conclusions; SALSA3D (SAndia LoS Alamos) Global 3D Earth Model for Travel Time; Comparison of IDC SSSCs to RSTT Predictions; SALSA3D; Validation and Model Comparison; DSS Lines in the Siberian Platform; DSS Line CRA-4 Comparison; Travel Time Δak135; Travel Time Prediction Uncertainty; SALSA3D Conclusions; Infrasound Data Processing: An example event; Infrasound Data Processing: An example event; Infrasound Location; How does BISL work?; BISL: Application to the 2013 DPRK Test; and BISL: Ongoing Research.

Epimicrobiota Associated with the Decay and Recovery of Orbicella Corals Exhibiting Dark Spot Syndrome

PubMed Central

Meyer, Julie L.; Rodgers, John M.; Dillard, Brian A.; Paul, Valerie J.; Teplitski, Max

2016-01-01

Dark Spot Syndrome (DSS) is one of the most common diseases of boulder corals in the Caribbean. It presents as sunken brown lesions in coral tissue, which can spread quickly over coral colonies. With this study, we tested the hypothesis that similar to other coral diseases, DSS is a dysbiosis characterized by global shifts in the coral microbiome. Because Black Band Disease (BBD) was sometimes found following DSS lesions, we also tested the hypothesis that DSS is a precursor of BBD. To track disease initiation and progression 24 coral colonies were tagged. Of them five Orbicella annularis corals and three O. faveolata corals exhibited DSS lesions at tagging. Microbiota of lesions and apparently healthy tissues from DSS-affected corals over the course of 18 months were collected. Final visual assessment showed that five of eight corals incurred substantial tissue loss while two corals remained stable and one appeared to recover from DSS lesions. Illumina sequencing of the V6 region of bacterial 16S rRNA genes demonstrated no significant differences in bacterial community composition associated with healthy tissue or DSS lesions. The epimicrobiomes of both healthy tissue and DSS lesions contained high relative abundances of Operational Taxonomic Units assigned to Halomonas, an unclassified gammaproteobacterial genus, Moritella, an unclassified Rhodobacteraceae genus, Renibacterium, Pseudomonas, and Acinetobacter. The relative abundance of bacterial taxa was not significantly different between samples when grouped by tissue type (healthy tissue vs. DSS lesion), coral species, collection month, or the overall outcome of DSS-affected corals (substantial tissue loss vs. stable/recovered). Two of the tagged corals with substantial tissue loss also developed BBD during the 18-month sampling period. The bacterial community of the BBD layer was distinct from both healthy tissue and DSS lesions, with high relative abundances of the presumed BBD pathogen Roseofilum reptotaenium and an unclassified Bacteroidales genus, similar to previous results. Roseofilum was detected in all samples from this study, with the highest relative abundance in healthy tissue from DSS-affected corals sampled in August, suggesting that while DSS is not a precursor to BBD, DSS-affected corals are in a weakened state and therefore more susceptible to additional infections. PMID:27375605

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

PubMed Central

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

2015-01-01

Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression. PMID:26381705

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

PubMed

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

2015-11-15

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

[Human body meridian spatial decision support system for clinical treatment and teaching of acupuncture and moxibustion].

PubMed

Wu, Dehua

2016-01-01

The spatial position and distribution of human body meridian are expressed limitedly in the decision support system (DSS) of acupuncture and moxibustion at present, which leads to the failure to give the effective quantitative analysis on the spatial range and the difficulty for the decision-maker to provide a realistic spatial decision environment. Focusing on the limit spatial expression in DSS of acupuncture and moxibustion, it was proposed that on the basis of the geographic information system, in association of DSS technology, the design idea was developed on the human body meridian spatial DSS. With the 4-layer service-oriented architecture adopted, the data center integrated development platform was taken as the system development environment. The hierarchical organization was done for the spatial data of human body meridian via the directory tree. The structured query language (SQL) server was used to achieve the unified management of spatial data and attribute data. The technologies of architecture, configuration and plug-in development model were integrated to achieve the data inquiry, buffer analysis and program evaluation of the human body meridian spatial DSS. The research results show that the human body meridian spatial DSS could reflect realistically the spatial characteristics of the spatial position and distribution of human body meridian and met the constantly changeable demand of users. It has the powerful spatial analysis function and assists with the scientific decision in clinical treatment and teaching of acupuncture and moxibustion. It is the new attempt to the informatization research of human body meridian.

Do Pre-Existing Diabetes Social Support or Depressive Symptoms Influence the Effectiveness of a Diabetes Management Intervention?

PubMed Central

Rosland, Ann-Marie; Kieffer, Edith; Spencer, Michael; Sinco, Brandy; Palmisano, Gloria; Valerio, Melissa; Nicklett, Emily; Heisler, Michele

2015-01-01

Objective Examine influences of diabetes-specific social support (D-SS) and depressive symptoms on glycemic control over time, among adults randomized to a diabetes self-management education and support (DSME/S) intervention or usual care. Methods Data were from 108 African-American and Latino participants in a six-month intervention trial. Multivariable linear regression models assessed associations between baseline D-SS from family and friends and depressive symptoms with changes in HbA1c. We then examined whether baseline D-SS or depression moderated intervention-associated effects on HbA1c. Results Higher baseline D-SS was associated with larger improvements in HbA1c (adjusted ΔHbA1c -0.39% for each +1-point D-SS, p=0.02), independent of intervention-associated HbA1c decreases. Baseline depressive symptoms had no significant association with subsequent HbA1c change. Neither D-SS nor depression moderated intervention-associated effects on HbA1c. Conclusions and Practice Implications Diabetes self-management education and support programs have potential to improve glycemic control for participants starting with varying levels of social support and depressive symptoms. Participants starting with more support for diabetes management from family and friends improved HbA1c significantly more over six months than those with less support, independent of additional significant DSME/S intervention-associated HbA1c improvements. Social support from family and friends may improve glycemic control in ways additive to DSME/S. PMID:26234800

An argument for the use of multiple segment stents in curved arteries.

PubMed

Kasiri, Saeid; Kelly, Daniel J

2011-08-01

Stenting of curved arteries is generally perceived to be more challenging than straight vessels. Conceptually implanting multiple shorter stents rather than a single longer stent into such a curved artery represents a promising concept, but little is known about the impact of such an approach. The objective of this study is to evaluate the effectiveness of using a multiple segment stent rather than a single long stent to dilate a curved artery using the finite element method. A double segment stent (DSS) and a single segment stent (SSS) were modeled. The stents were compared when expanded into a model of a curved artery. The model predicts that the DSS provides higher flexibility, more conformity, and lower recoil in comparison to the SSS. The volume of arterial tissue experiencing high levels of stress due to stent implantation is also reduced for the DSS. It is suggested that a multiple segment stenting system is a potential solution to the problem of higher rates of in-stent restenosis in curved arteries and mechanically challenging environments.

The integration of quantitative information with an intelligent decision support system for residential energy retrofits

NASA Astrophysics Data System (ADS)

Mo, Yunjeong

The purpose of this research is to support the development of an intelligent Decision Support System (DSS) by integrating quantitative information with expert knowledge in order to facilitate effective retrofit decision-making. To achieve this goal, the Energy Retrofit Decision Process Framework is analyzed. Expert system shell software, a retrofit measure cost database, and energy simulation software are needed for developing the DSS; Exsys Corvid, the NREM database and BEopt were chosen for implementing an integration model. This integration model demonstrates the holistic function of a residential energy retrofit system for existing homes, by providing a prioritized list of retrofit measures with cost information, energy simulation and expert advice. The users, such as homeowners and energy auditors, can acquire all of the necessary retrofit information from this unified system without having to explore several separate systems. The integration model plays the role of a prototype for the finalized intelligent decision support system. It implements all of the necessary functions for the finalized DSS, including integration of the database, energy simulation and expert knowledge.

Preliminary maintenance experience for DSS 13 unattended operations demonstration. [Deep Space Network

NASA Technical Reports Server (NTRS)

Remer, D. S.; Lorden, G.

1979-01-01

The maintenance data base collected for 15 weeks of recent unattended and automated operation of DSS 13 is summarized. During this period, DSS 13 was receiving spacecraft telemetry while being controlled remotely from JPL in Pasadena. Corrective and preventive maintenance manhours are reported by subsystem for DSS 13 including the equipment added for the automation demonstration. The corrective and preventive maintenance weekly manhours at DSS 13 averaged 22 and 40, respectively. The antenna hydraulic and electronic systems accounted for about half of the preventive and corrective maintenance manhours for a comparable attended DSN station, DSS 11.

Experimental study on agitated drying characteristics of sewage sludge under the effects of different additive agents.

PubMed

Deng, Wenyi; Su, Yaxin

2014-07-01

Drying experiments of dewatered sewage sludge (DSS) were conducted on a agitated paddle dryer, and the effects of additive agents, i.e., CaO, pulverized coal (PC), heavy oil (HO), and dried sludge ("DS" through back mixing) on the agitated drying characteristics of DSS were investigated. The results indicated that CaO can significantly increase the drying rate of DSS. The drying rate at CaO/DSS (mass ratio)=1/100 was 135% higher than that of CaO/DSS=0. Pulverized coal has no obvious effect on drying rate, but the increase of PC/DSS can promote breaking up of sludge lump. Heavy oil was found to be slightly effective in improving the drying rate of DSS in the examined experimental range of HO/DSS=0-1/20. It is also found that HO can reduce the torque of the dryer shaft, due to its lubrication effect. Back mixing of DS was found to be effective in alleviating the unfavorable effect of the lumpy phase by improving the mixing effect of the paddle dryer. There was a marked increase of drying rate with an increase of the DS/DSS in the experimental range of DS/DSS=0-1/3. Copyright © 2014. Published by Elsevier B.V.

Integrating economy, ecology and uncertainty in an oil-spill DSS: The Prestige accident in Spain, 2002

NASA Astrophysics Data System (ADS)

Wirtz, Kai W.; Liu, Xin

2006-12-01

Major accidental oil spills still affect sensitive marine areas and shorelines around the world, constituting a challenge for operational as well as strategic contingency management. As a rationale basis for addressing both issues we here propose a Decision Support System (DSS) consisting of a combination of modelling and evaluation methods which in particular assesses various impacts on habitats and local economies. By integrating the state-of-the-art oil spill contingency simulation system OSCAR with wind and current forecasts, environmental GIS data and multi-criteria analysis techniques, the DSS is able to rank different response actions to a chemical or oil spill. In this study, the usefulness of the approach is tested by hindcasting the Prestige accident off the coast of Spain in 2002. In particular, the short- to mid-term economic and ecological consequences of different mitigation measures are estimated. We identified clearly one worst option matching the actual decision taken by the responsible parties and one or two almost equally well performing routes. Two procedures of including uncertainty at various stages of the DSS are tested. The first method averages ensembles of outcomes between each modelling/evaluation stage, while the second one preserves the entire degree of freedom till the final ranking procedure. Results in the Prestige case turned out to be rather insensitive against both ways to account for uncertainties. The robustness as well as clarity of the DSS has the potential to enhance the efficiency of decision making even in politically sensitive situations. Limitations as well as ongoing improvements of the system are highlighted, in particular emphasizing linkages to environmental economics.

Serum Amino Acids Profile and the Beneficial Effects of L-Arginine or L-Glutamine Supplementation in Dextran Sulfate Sodium Colitis

PubMed Central

Wu, Miaomiao; Liu, Gang; Yang, Guan; Xion, Yan; Su, Dingding; Wu, Li; Li, Tiejun; Chen, Shuai; Duan, Jielin; Yin, Yulong; Wu, Guoyao

2014-01-01

This study was conducted to investigate serum amino acids profile in dextran sulfate sodium (DSS)-induced colitis, and impacts of graded dose of arginine or glutamine supplementation on the colitis. Using DSS-induced colitis model, which is similar to human ulcerative colitis, we determined serum profile of amino acids at day 3, 7, 10 and 12 (5 days post DSS treatment). Meanwhile, effects of graded dose of arginine (0.4%, 0.8%, and 1.5%) or glutamine (0.5%, 1.0% and 2.0%) supplementation on clinical parameters, serum amino acids, colonic tight junction proteins, colonic anti-oxidative indicators [catalase, total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px)], colonic pro-inflammatory cytokines [interleukin-1 beta (IL-1β), IL-6, IL-17 and tumor necrosis factor alpha (TNF-α)] in DSS-induced colitis were fully analyzed at day 7 and 12. Additionally, the activation of signal transduction pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPK), phosphoinositide-3-kinases (PI3K)/PI3K-protein kinase B (Akt), and myosin light chain kinase (MLCK)- myosin light chain (MLC20), were analyzed using immunoblotting. Serum amino acids analysis showed that DSS treatment changed the serum contents of amino acids, such as Trp, Glu, and Gln (P<0.05). Dietary arginine or glutamine supplementation had significant (P<0.05) influence on the clinical and biochemical parameters (T-SOD, IL-17 and TNF-α) in colitis model. These results were associated with colonic NF-κB, PI3K-Akt and MLCK signaling pathways. In conclusion, arginine or glutamine could be a potential therapy for intestinal inflammatory diseases. PMID:24505477

Serum amino acids profile and the beneficial effects of L-arginine or L-glutamine supplementation in dextran sulfate sodium colitis.

PubMed

Ren, Wenkai; Yin, Jie; Wu, Miaomiao; Liu, Gang; Yang, Guan; Xion, Yan; Su, Dingding; Wu, Li; Li, Tiejun; Chen, Shuai; Duan, Jielin; Yin, Yulong; Wu, Guoyao

2014-01-01

This study was conducted to investigate serum amino acids profile in dextran sulfate sodium (DSS)-induced colitis, and impacts of graded dose of arginine or glutamine supplementation on the colitis. Using DSS-induced colitis model, which is similar to human ulcerative colitis, we determined serum profile of amino acids at day 3, 7, 10 and 12 (5 days post DSS treatment). Meanwhile, effects of graded dose of arginine (0.4%, 0.8%, and 1.5%) or glutamine (0.5%, 1.0% and 2.0%) supplementation on clinical parameters, serum amino acids, colonic tight junction proteins, colonic anti-oxidative indicators [catalase, total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px)], colonic pro-inflammatory cytokines [interleukin-1 beta (IL-1β), IL-6, IL-17 and tumor necrosis factor alpha (TNF-α)] in DSS-induced colitis were fully analyzed at day 7 and 12. Additionally, the activation of signal transduction pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPK), phosphoinositide-3-kinases (PI3K)/PI3K-protein kinase B (Akt), and myosin light chain kinase (MLCK)-myosin light chain (MLC20), were analyzed using immunoblotting. Serum amino acids analysis showed that DSS treatment changed the serum contents of amino acids, such as Trp, Glu, and Gln (P<0.05). Dietary arginine or glutamine supplementation had significant (P<0.05) influence on the clinical and biochemical parameters (T-SOD, IL-17 and TNF-α) in colitis model. These results were associated with colonic NF-κB, PI3K-Akt and MLCK signaling pathways. In conclusion, arginine or glutamine could be a potential therapy for intestinal inflammatory diseases.

A novel Toll-like receptor 4 antagonist antibody ameliorates inflammation but impairs mucosal healing in murine colitis

PubMed Central

Ungaro, Ryan; Fukata, Masayuki; Hsu, David; Hernandez, Yasmin; Breglio, Keith; Chen, Anli; Xu, Ruliang; Sotolongo, John; Espana, Cecillia; Zaias, Julia; Elson, Greg; Mayer, Lloyd; Kosco-Vilbois, Marie; Abreu, Maria T.

2009-01-01

Dysregulated innate immune responses to commensal bacteria contribute to the development of inflammatory bowel disease (IBD). TLR4 is overexpressed in the intestinal mucosa of IBD patients and may contribute to uncontrolled inflammation. However, TLR4 is also an important mediator of intestinal repair. The aim of this study is to examine the effect of a TLR4 antagonist on inflammation and intestinal repair in two murine models of IBD. Colitis was induced in C57BL/6J mice with dextran sodium sulfate (DSS) or by transferring CD45Rbhi T cells into RAG1−/− mice. An antibody (Ab) against the TLR4/MD-2 complex or isotype control Ab was administered intraperitoneally during DSS treatment, recovery from DSS colitis, or induction of colitis in RAG1−/− mice. Colitis severity was assessed by disease activity index (DAI) and histology. The effect of the Ab on the inflammatory infiltrate was determined by cell isolation and immunohistochemistry. Mucosal expression of inflammatory mediators was analyzed by real-time PCR and ELISA. Blocking TLR4 at the beginning of DSS administration delayed the development of colitis with significantly lower DAI scores. Anti-TLR4 Ab treatment decreased macrophage and dendritic cell infiltrate and reduced mucosal expression of CCL2, CCL20, TNF-α, and IL-6. Anti-TLR4 Ab treatment during recovery from DSS colitis resulted in defective mucosal healing with lower expression of COX-2, PGE2, and amphiregulin. In contrast, TLR4 blockade had minimal efficacy in ameliorating inflammation in the adoptive transfer model of chronic colitis. Our findings suggest that anti-TLR4 therapy may decrease inflammation in IBD but may also interfere with colonic mucosal healing. PMID:19359427

Stress activates pronociceptive endogenous opioid signalling in DRG neurons during chronic colitis.

PubMed

Guerrero-Alba, Raquel; Valdez-Morales, Eduardo E; Jimenez-Vargas, Nestor N; Lopez-Lopez, Cintya; Jaramillo-Polanco, Josue; Okamoto, Takanobu; Nasser, Yasmin; Bunnett, Nigel W; Lomax, Alan E; Vanner, Stephen J

2017-12-01

Psychological stress accompanies chronic inflammatory diseases such as IBD, and stress hormones can exacerbate pain signalling. In contrast, the endogenous opioid system has an important analgesic action during chronic inflammation. This study examined the interaction of these pathways. Mouse nociceptive dorsal root ganglia (DRG) neurons were incubated with supernatants from segments of inflamed colon collected from patients with chronic UC and mice with dextran sodium sulfate (cDSS)-induced chronic colitis. Stress effects were studied by adding stress hormones (epinephrine and corticosterone) to dissociated neurons or by exposing cDSS mice to water avoidance stress. Changes in excitability of colonic DRG nociceptors were measured using patch clamp and Ca 2+ imaging techniques. Supernatants from patients with chronic UC and from colons of mice with chronic colitis caused a naloxone-sensitive inhibition of neuronal excitability and capsaicin-evoked Ca 2+ responses. Stress hormones decreased signalling induced by human and mouse supernatants. This effect resulted from stress hormones signalling directly to DRG neurons and indirectly through signalling to the immune system, leading to decreased opioid levels and increased acute inflammation. The net effect of stress was a change endogenous opioid signalling in DRG neurons from an inhibitory to an excitatory effect. This switch was associated with a change in G protein-coupled receptor excitatory signalling to a pathway sensitive to inhibitors of protein kinase A-protein, phospholipase C-protein and G protein βϒ subunits. Stress hormones block the inhibitory actions of endogenous opioids and can change the effect of opioid signalling in DRG neurons to excitation. Targeting these pathways may prevent heavy opioid use in IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Decision Support System for Coastal Protection Layout Design (DSS4CPD) Using Genetic Algorithm (ga) and Multicriteria Analysis (mca)

NASA Astrophysics Data System (ADS)

Jinchai, Phinai; Chittaladakorn, Suwatana

This research has its objective to develop the decision support system on GIS to be used in the coastal erosion protection management. The developed model in this research is called Decision Support System for Coastal Protection Layout Design (DSS4CPD). It has created both for systematic protection and solution measures to the problem by using Genetic Algorithm (GA) and Multicriteria Analysis (MCA) for finding the coastal structure layout optimal solution. In this research, three types of coastal structures were used as structure alternatives for the layout, which are seawall, breakwater, and groin. The coastal area in Nakornsrithammaraj, Thailand was used as the case study. The studied result has found the appropriate position of coastal structures considering the suitable rock size relied on the wave energy, and the appropriate coastal structure position based on the wave breaking line. Using GA and MCA in DSS4CPD, it found the best layout in this project. This DSS4CPD will be used by the authorized decision makers to find the most suitable erosion problem solution.

Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry.

PubMed

Zhao, Weixing; Vaithiyalingam, Sivaraja; San Filippo, Joseph; Maranon, David G; Jimenez-Sainz, Judit; Fontenay, Gerald V; Kwon, Youngho; Leung, Stanley G; Lu, Lucy; Jensen, Ryan B; Chazin, Walter J; Wiese, Claudia; Sung, Patrick

2015-07-16

The tumor suppressor BRCA2 is thought to facilitate the handoff of ssDNA from replication protein A (RPA) to the RAD51 recombinase during DNA break and replication fork repair by homologous recombination. However, we find that RPA-RAD51 exchange requires the BRCA2 partner DSS1. Biochemical, structural, and in vivo analyses reveal that DSS1 allows the BRCA2-DSS1 complex to physically and functionally interact with RPA. Mechanistically, DSS1 acts as a DNA mimic to attenuate the affinity of RPA for ssDNA. A mutation in the solvent-exposed acidic domain of DSS1 compromises the efficacy of RPA-RAD51 exchange. Thus, by targeting RPA and mimicking DNA, DSS1 functions with BRCA2 in a two-component homologous recombination mediator complex in genome maintenance and tumor suppression. Our findings may provide a paradigm for understanding the roles of DSS1 in other biological processes. Copyright © 2015 Elsevier Inc. All rights reserved.

Sex determining gene on the X chromosome short arm: dosage sensitive sex reversal.

PubMed

Ogata, T; Matsuo, N

1996-08-01

The present review article summarizes current knowledge concerning the sex determining gene on Xp21, termed DSS (dosage sensitive sex reversal). The presence of DSS has been based on the finding that, in the presence of SRY, partial active Xp duplications encompassing the middle part of Xp result in sex reversal, whereas those of the distal or proximal part of Xp permit male sex development. Because Klinefelter patients develop as males, it is believed that DSS is normally subject to X-inactivation, and that two active copies of DSS override the function of SRY, resulting in gonadal dysgenesis because of meiotic pairing failure. It may be possible that DSS encodes a target sequence for repressing function of SRY or that DSS is involved in an X chromosome-counting mechanism. Molecular approaches have localized DSS to a 160 kb region and isolated candidate genes such as DAX-1 and MAGE-Xp, but there has been no formal evidence equating the candidate gene with DSS. In addition to its clinical importance, the exploration of DSS must provide a useful clue to phylogenetic studies of sex chromosomes and dosage compensation.

Chronic Supplementation of Paeonol Combined with Danshensu for the Improvement of Vascular Reactivity in the Cerebral Basilar Artery of Diabetic Rats

PubMed Central

Hu, Jing; Li, Ya-Ling; Li, Zi-Lin; Li, Hua; Zhou, Xuan-Xuan; Qiu, Peng-Cheng; Yang, Qian; Wang, Si-Wang

2012-01-01

One of the leading causes of death in the world is cerebrovascular disease. Numerous Chinese traditional medicines, such as Cortex Moutan (root bark of Paeonia suffruticosa Andrew) and Radix Salviae miltiorrhizae (root and rhizome of Salvia miltiorrhiza Bunge), protect against cerebrovascular diseases and exhibit anti-atherosclerotic effects. Traditional medicines have been routinely used for a long time in China. In addition, these two herbs are prescribed together in clinical practice. Therefore, the pharmacodynamic interactions between the active constituents of these two herbs, which are paeonol (Pae) and danshensu (DSS), should be particularly studied. The study of Pae and DSS can provide substantial foundations in understanding their mechanisms and empirical evidence to support clinical practice. This study investigated the effects and possible mechanisms of the pharmacodynamic interaction between Pae and DSS on cerebrovascular malfunctioning in diabetes. Experimental diabetes was induced in rats, which was then treated with Pae, DSS, and Pae + DSS for eight weeks. Afterward, cerebral arteries from all groups were isolated and equilibrated in an organ bath with Krebs buffer and ring tension. Effects of Pae, DSS, and Pae + DSS were observed on vessel relaxation with or without endothelium as well as on the basal tonus of vessels from normal and diabetic rats. Indexes about oxidative stress were also determined. We report that the cerebral arteries from diabetic rats show decreased vascular reactivity to acetylcholine (ACh) which was corrected in Pae, DSS, and Pae + DSS treated groups. Furthermore, phenylephrine (PE)-induced contraction response decreased in the treated groups. Phenylephrine and CaCl2-induced vasoconstrictions are partially inhibited in the three treated groups under Ca2+-free medium. Pre-incubated with tetraethylammonium, a non-selective K+ channel blocker, the antagonized relaxation responses increased in DSS and Pae + DSS treated diabetic groups compared with those in diabetic and Pae-treated diabetic groups. In addition, superoxide dismutase activity and thiobarbituric acid reactive substances content significantly changed in the presence of Pae + DSS. We therefore conclude that both Pae and DSS treatments prevent diabetes-induced vascular damage. Furthermore, Pae + DSS prove to be the most efficient treatment regimen. The combination of Pae and DSS produce significant protective effects through the reduction of oxidative stress and through intracellular Ca2+ regulatory mechanisms. PMID:23203081

The dynamics of life stressors and depressive symptoms in early adolescence: a test of six theoretical models.

PubMed

Clements, Margaret; Aber, J Lawrence; Seidman, Edward

2008-01-01

Structural equation modeling was used to compare 6 competing theoretically based psychosocial models of the longitudinal association between life stressors and depressive symptoms in a sample of early adolescents (N= 907; 40% Hispanic, 32% Black, and 19% White; mean age at Time 1 = 11.4 years). Only two models fit the data, both of which included paths modeling the effect of depressive symptoms on stressors recall: The mood-congruent cognitive bias model included only depressive symptoms to life stressors paths (DS-->S), whereas the fully transactional model included paths representing both the DS-->S and stressors to depressive symptoms (S-->DS) effects. Social causation models and the stress generation model did not fit the data. Findings demonstrate the importance of accounting for mood-congruent cognitive bias in stressors-depressive symptoms investigations.

Glutamine supplementation attenuates expressions of adhesion molecules and chemokine receptors on T cells in a murine model of acute colitis.

PubMed

Hou, Yu-Chen; Wu, Jin-Ming; Wang, Ming-Yang; Wu, Ming-Hsun; Chen, Kuen-Yuan; Yeh, Sung-Ling; Lin, Ming-Tsan

2014-01-01

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

Suppressive effect of pectic polysaccharides extracted from Rauwolfia verticillata (Lour.) Baill.var.hainanensis Tsiang on inflammation by regulation of NF- κ B pathway and interleukin-17 in mice with dextran sulphatesodium-induced ulcerative colitis.

PubMed

Miao, Xin-Pu; Sun, Xiao-Ning; Cui, Lu-Jia; Cao, Qin-Fang; Zhuang, Gui-Feng; Deng, Tao-Zhi; Zhang, Dong-Yan

2015-02-01

To investigate the effects of pectic polysaccharides extracted from Rauwolfia verticillata (Lour.) Baill.var.hainanensis Tsiang on an experimental murine colitis model. Experimental colitis was induced by dextran sulfate sodium (DSS), and mice were divided into 4 groups: control, DSS alone, DSS plus SASP, DSS plus pectic polysaccharides. The disease activity index (DAI) and histological score were observed. The tumor necrosis factor (TNF)- α and interleukin (IL)-17 levels were measured by enzyme-linked immunosorbent assay. I κ B and NF- κ B p65 expression were assessed by western blot analysis. Myeloperoxidase (MPO) activity was determined by using MPO assay kit. Administration of pectic polysaccharides significantly reduced the severity of DSS-induced colitis as assessed by DAI and histological score, and resulted in down regulation of MPO activity and NF- κ B p65 expression and subsequent degradation of I κ B protein, strikingly reduced the production of TNF- a and IL-17. Pectic polysaccharides extracted from Rauvolfia verticillata (Lour.)Baill.var. hainanensis Tsiang exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Dextran Sulfate Sodium-Induced Colonic Histopathology, but not Altered Epithelial Ion Transport, Is Reduced by Inhibition of Phosphodiesterase Activity

PubMed Central

Diaz-Granados, Natalia; Howe, Kathryn; Lu, Jun; McKay, Derek M.

2000-01-01

Inhibition of phosphodiesterase (PDE) activity is beneficial in models of arthritis and airway inflammation. Here we assessed the ability of PDE inhibitors to modulate colitis by exposing mice to 4% (w/v) dextran sulfate sodium (DSS) drinking water for 5 days with or without rolipram, an inhibitor of PDE type 4, or the nonselective PDE inhibitor, pentoxifylline (both at 5 mg/kg, i.p., twice daily). Controls received saline, vehicle, or drug only. Colonic histology, myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) levels, and epithelial ion transport (baseline and stimulated by electrical nerve stimulation, carbachol, and forskolin) were examined. DSS-treated mice displayed a variable diarrhea, significant histopathology in the mid-distal colon, elevated MPO activity, and reduced (>50%) responses to all three pro-secretory stimuli. Treatment with rolipram, and to a lesser extent pentoxifylline, significantly reduced the severity of the colonic histopathology and MPO levels. Neither PDE inhibitor had any affect on the diminished ion transport events caused by DSS-induced colitis. However, although stimulated ion transport events were still reduced 3 days after DSS treatment, colonic segments from DSS + rolipram-treated mice displayed enhanced recovery in their secretory responsiveness, particularly to carbachol. These findings indicate that specific PDE4 inhibition can significantly reduce the tissue damage that accompanies colitis and enhance recovery of normal colonic function. PMID:10854237

Collaboration in River Basin Management: The Great Rivers Project

NASA Astrophysics Data System (ADS)

Crowther, S.; Vridhachalam, M.; Tomala-Reyes, A.; Guerra, A.; Chu, H.; Eckman, B.

2008-12-01

The health of the world's freshwater ecosystems is fundamental to the health of people, plants and animals around the world. The sustainable use of the world's freshwater resources is recognized as one of the most urgent challenges facing society today. An estimated 1.3 billion people currently lack access to safe drinking water, an issue the United Nations specifically includes in its recently published Millennium Development Goals. IBM is collaborating with The Nature Conservancy and the Center for Sustainability and the Global Environment (SAGE) at the University of Wisconsin, Madison to build a Modeling Collaboration Framework and Decision Support System (DSS) designed to help policy makers and a variety of stakeholders (farmers, fish and wildlife managers, hydropower operators, et al.) to assess, come to consensus, and act on land use decisions representing effective compromises between human use and ecosystem preservation/restoration efforts. Initially focused on Brazil's Paraguay-Parana, China's Yangtze, and the Mississippi Basin in the US, the DSS integrates data and models from a wide variety of environmental sectors, including water balance, water quality, carbon balance, crop production, hydropower, and biodiversity. In this presentation we focus on the collaboration aspects of the DSS. The DSS is an open environment tool that allows scientists, policy makers, politicians, land owners, and anyone who desires to take ownership of their actions in support of the environment to work together to that end. The DSS supports a range of features that empower such a community to collaboratively work together. Supported collaboration mediums include peer reviews, live chat, static comments, and Web 2.0 functionality such as tagging. In addition, we are building a 3-D virtual world component which will allow users to experience and share system results, first-hand. Models and simulation results may be annotated with free-text comments and tags, whether unique or chosen from a predefined tag taxonomy. These comments and tag clouds may be used by the community to filter results and identify models or simulations of interest, e.g, by region, modeling approach, spatiotemporal resolution, etc. Users may discuss methods or results in real-time with a built-in chat feature. Separate user groups may be defined for logical groups of collaboration partners, e.g., expert modelers, land managers, policy makers, school children, or the general public, to optimize the collaboration signal-to-noise ratio for all.

FLIRE DSS: A web tool for the management of floods and wildfires in urban and periurban areas

NASA Astrophysics Data System (ADS)

Kochilakis, Giorgos; Poursanidis, Dimitris; Chrysoulakis, Nektarios; Varella, Vassiliki; Kotroni, Vassiliki; Eftychidis, Giorgos; Lagouvardos, Kostas; Papathanasiou, Chrysoula; Karavokyros, George; Aivazoglou, Maria; Makropoulos, Christos; Mimikou, Maria

2016-01-01

A web-based Decision Support System, named FLIRE DSS, for combined forest fire control and planning as well as flood risk management, has been developed and is presented in this paper. State of the art tools and models have been used in order to enable Civil Protection agencies and local stakeholders to take advantage of the web based DSS without the need of local installation of complex software and their maintenance. Civil protection agencies can predict the behavior of a fire event using real time data and in such a way plan its efficient elimination. Also, during dry periods, agencies can implement "what-if" scenarios for areas that are prone to fire and thus have available plans for forest fire management in case such scenarios occur. Flood services include flood maps and flood-related warnings and become available to relevant authorities for visualization and further analysis on a daily basis. When flood warnings are issued, relevant authorities may proceed to efficient evacuation planning for the areas that are likely to flood and thus save human lives. Real-time weather data from ground stations provide the necessary inputs for the calculation of the fire model in real-time, and a high resolution weather forecast grid supports flood modeling as well as the development of "what-if" scenarios for the fire modeling. All these can be accessed by various computer sources including PC, laptop, Smartphone and tablet either by normal network connection or by using 3G and 4G cellular network. The latter is important for the accessibility of the FLIRE DSS during firefighting or rescue operations during flood events. All these methods and tools provide the end users with the necessary information to design an operational plan for the elimination of the fire events and the efficient management of the flood events in almost real time. Concluding, the FLIRE DSS can be easily transferred to other areas with similar characteristics due to its robust architecture and its flexibility.

5-fluorouracil attenuates dextran sodium sulfate-induced acute colitis in mice.

PubMed

Xiao, Junhua; Lu, Zhanjun; Sheng, Jiaqing; Song, Yunna; Jiang, Weiliang; Liu, Fei; Zheng, Ping

2016-03-01

5‑Fluorouracil (5‑FU) has been predominantly used in the clinic for cancer chemotherapy. Previous studies have demonstrated that 5‑FU has an anti‑inflammatory function. In the current study, the potential therapeutic role of 5‑FU in dextran sodium sulfate (DSS)‑induced acute mouse colitis was investigated. Effects on the severity of colitis were studied via histochemical and immunohistochemical staining, cytokine levels were determined by reverse transcriptoin‑quantitative polymerase chain reaction and the effect of 5‑FU on NF‑κB was examined by western blotting. Administration of 5‑FU ameliorated the severity of acute DSS‑induced colitis. The disease activity score was significantly lower in the 5‑FU + DSS‑treated mice compared with the DSS‑treated group (P<0.01). Tumor necrosis factor‑α, interleukin‑1β and interferon γ mRNA expression levels were significantly downregulated in the colon tissue of DSS mice treated with 5‑FU compared with the untreated DSS mice (P<0.05). In addition, the number of CD4+ T cells in the colonic lamina propria and myeloperoxidase activity were significantly decreased in the 5‑FU + DSS‑treated mice (P<0.05). Furthermore, 5‑FU treatment significantly reduced p‑NF‑κB‑p56 protein expression levels in the colon tissue of DSS‑treated mice (P<0.05). The present results demonstrated that 5‑FU minimizes the abnormal immune cytokine response and relieves the pathophysiological disorders associated with experimental acute colitis. Thus, the modulating inflammatory response role of 5‑FU may be partially associated with inhibiting NF‑κB activation and 5‑FU may be a novel therapeutic strategy for the treatment of inflammatory bowel disease.

A multiple-scenario assessment of the effect of a continuous-care, guideline-based decision support system on clinicians' compliance to clinical guidelines.

PubMed

Shalom, Erez; Shahar, Yuval; Parmet, Yisrael; Lunenfeld, Eitan

2015-04-01

To quantify the effect of a new continuous-care guideline (GL)-application engine, the Picard decision support system (DSS) engine, on the correctness and completeness of clinicians' decisions relative to an established clinical GL, and to assess the clinicians' attitudes towards a specific DSS. Thirty-six clinicians, including residents at different training levels and board-certified specialists at an academic OB/GYN department that handles around 15,000 deliveries annually, agreed to evaluate our continuous-care guideline-based DSS and to perform a cross-over assessment of the effects of using our guideline-based DSS. We generated electronic patient records that realistically simulated the longitudinal course of six different clinical scenarios of the preeclampsia/eclampsia/toxemia (PET) GL, encompassing 60 different decision points in total. Each clinician managed three scenarios manually without the Picard DSS engine (Non-DSS mode) and three scenarios when assisted by the Picard DSS engine (DSS mode). The main measures in both modes were correctness and completeness of actions relative to the PET GL. Correctness was further decomposed into necessary and redundant actions, relative to the guideline and the actual patient data. At the end of the assessment, a questionnaire was administered to the clinicians to assess their perceptions regarding use of the DSS. With respect to completeness, the clinicians applied approximately 41% of the GL's recommended actions in the non-DSS mode. Completeness increased to the performance of approximately 93% of the guideline's recommended actions, when using the DSS mode. With respect to correctness, approximately 94.5% of the clinicians' decisions in the non-DSS mode were correct. However, these included 68% of the actions that were correct but redundant, given the patient's data (e.g., repeating tests that had been performed), and 27% of the actions, which were necessary in the context of the GL and of the given scenario. Only 5.5% of the decisions were definite errors. In the DSS mode, 94% of the clinicians' decisions were correct, which included 3% that were correct but redundant, and 91% of the actions that were correct and necessary in the context of the GL and of the given scenario. Only 6% of the DSS-mode decisions were erroneous. The DSS was assessed by the clinicians as potentially useful. Support from the GL-based DSS led to uniformity in the quality of the decisions, regardless of the particular clinician, any particular clinical scenario, any particular decision point, or any decision type within the scenarios. Using the DSS dramatically enhances completeness (i.e., performance of guideline-based recommendations) and seems to prevent the performance of most of the redundant actions, but does not seem to affect the rate of performance of incorrect actions. The redundancy rate is enhanced by similar recent findings in recent studies. Clinicians mostly find this support to be potentially useful for their daily practice. A continuous-care GL-based DSS, such as the Picard DSS engine, has the potential to prevent most errors of omission by ensuring uniformly high quality of clinical decision making (relative to a GL-based norm), due to the increased adherence (i.e., completeness) to the GL, and most of the errors of commission that increase therapy costs, by reducing the rate of redundant actions. However, to prevent clinical errors of commission, the DSS needs to be accompanied by additional modules, such as automated control of the quality of the physician's actual actions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Real-time antenna fault diagnosis experiments at DSS 13

NASA Technical Reports Server (NTRS)

Mellstrom, J.; Pierson, C.; Smyth, P.

1992-01-01

Experimental results obtained when a previously described fault diagnosis system was run online in real time at the 34-m beam waveguide antenna at Deep Space Station (DSS) 13 are described. Experimental conditions and the quality of results are described. A neural network model and a maximum-likelihood Gaussian classifier are compared with and without a Markov component to model temporal context. At the rate of a state update every 6.4 seconds, over a period of roughly 1 hour, the neural-Markov system had zero errors (incorrect state estimates) while monitoring both faulty and normal operations. The overall results indicate that the neural-Markov combination is the most accurate model and has significant practical potential.

A multicriteria decision making model for assessment and selection of an ERP in a logistics context

NASA Astrophysics Data System (ADS)

Pereira, Teresa; Ferreira, Fernanda A.

2017-07-01

The aim of this work is to apply a methodology of decision support based on a multicriteria decision analyses (MCDA) model that allows the assessment and selection of an Enterprise Resource Planning (ERP) in a Portuguese logistics company by Group Decision Maker (GDM). A Decision Support system (DSS) that implements a MCDA - Multicriteria Methodology for the Assessment and Selection of Information Systems / Information Technologies (MMASSI / IT) is used based on its features and facility to change and adapt the model to a given scope. Using this DSS it was obtained the information system that best suited to the decisional context, being this result evaluated through a sensitivity and robustness analysis.

Water Plan 2030: A Dynamic Education Model for Teaching Water Management Issues

NASA Astrophysics Data System (ADS)

Rupprecht, C.; Washburne, J.; Lansey, K.; Williams, A.

2006-12-01

Dynamic educational tools to assist teachers and students in recognizing the impacts of water management decisions in a realistic context are not readily available. Water policy issues are often complex and difficult for students trying to make meaningful connections between system components. To fill this need, we have developed a systems modeling-based educational decision support system (DSS) with supplementary materials. This model, called Water Plan 2030, represents a general semi-arid watershed; it allows users to examine water management alternatives by changing input values for various water uses and basin conditions and immediately receive graphical outputs to compare decisions. The main goal of our DSS model is to foster students' abilities to make knowledgeable decisions with regard to water resources issues. There are two reasons we have developed this model for traditional classroom settings. First, the DSS model provides teachers with a mechanism for educating students about inter-related hydrologic concepts, complex systems and facilitates discussion of water resources issues. Second, Water Plan 2030 encourages student discovery of cause/effect relationships in a dynamic, hands-on environment and develops the ability to realize the implications of water management alternatives. The DSS model has been utilized in an undergraduate, non-major science class for 5 course hours, each of the past 4 semesters. Accompanying the PC-based model are supplementary materials to improve the effectiveness of implementation by emphasizing important concepts and guiding learners through the model components. These materials include in-class tutorials, introductory questions, role-playing activities and homework extensions that have been revised after each user session, based on student and instructor feedback. Most recently, we have developed individual lessons that teach specific model functions and concepts. These modules provide teachers the flexibility to adapt the model to meet numerous teaching goals. Evaluation results indicate that students improved their understanding of fundamental concepts and system interactions and showed the most improvement in questions related to water use by sector and sustainability issues. Model modifications have also improved student feedback of the model effectiveness and user- friendliness. Positive results from this project have created the demand for a web-based version, which will be online in late 2006.

Oncologic outcomes in patients with nonurothelial bladder cancer.

PubMed

Patel, Sanjay G; Weiner, Adam Benjamin; Keegan, Kirk; Morgan, Todd

2018-01-01

We aimed to evaluate the relative prognostic impact of the most common variant histologies on disease-specific survival (DSS) in patients undergoing radical cystectomy. The Surveillance, Epidemiology, and End Result database was used to identify patients who underwent radical cystectomy for bladder cancer from 1990 to 2007. Patients with urothelial cell carcinoma (UCC), squamous cell carcinoma (SCC), adenocarcinoma (AC), sarcoma, small cell carcinoma, signet ring carcinoma, and spindle cell carcinoma were included in the study. Multivariable analysis was performed using Cox proportional hazards model to assess independent predictors of disease-specific survival (DSS). Mortality rates were estimated using Kaplan-Meier analyses. A total of 14,130 patients met inclusion criteria with the following histologies: UCC (90.1%), SCC (4.6%), AC, (2.3%), sarcoma (0.8%), small cell carcinoma (0.8%), signet ring carcinoma (0.5%), and spindle cell carcinoma (0.9%). Three-year DSS was most favorable in patients with UCC (63.7%; 95% confidence interval [62.9%-64.8%]) and AC (65.3% [59.3%-70.6%]), whereas 3-year DSS was the least favorable for small cell carcinoma (41.6% [31.3%-51.6%]) and sarcoma (45.4% [35.1%-55.1%]). In the multivariable analysis, independent predictors of DSS were age, marital status, grade, T-stage, N-stage, and variant histology. With respect to UCC, there was an increased risk of disease-specific death associated with all variants except AC. Sarcoma and spindle cell carcinoma were associated with the highest risk of death. With the exception of AC, the most common variant bladder cancer histologies are all independently associated with worse DSS relative to UCC in patients undergoing radical cystectomy.

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

PubMed

Barrett, Kim E; McCole, Declan F

2016-11-01

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

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

PubMed Central

Barrett, Kim E.; McCole, Declan F.

2016-01-01

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

Cathelicidin Signaling via the Toll-Like Receptor Protects Against Colitis in Mice

PubMed Central

Koon, Hon Wai; Shih, David Quan; Chen, Jeremy; Bakirtzi, Kyriaki; Hing, Tressia C; Law, Ivy; Ho, Samantha; Ichikawa, Ryan; Zhao, Dezheng; Xu, Hua; Gallo, Richard; Dempsey, Paul; Cheng, Genhong; Targan, Stephan R; Pothoulakis, Charalabos

2011-01-01

Background & Aims Cathelicidin (encoded by Camp) is an anti-microbial peptide in the innate immune system. We examined whether macrophages express cathelicidin in colons of mice with experimental colitis and patients with inflammatory bowel disease; we investigated its signaling mechanisms. Methods Quantitative, real-time, reverse transcription PCR, bacterial 16S PCR, immunofluorescence, and small interfering (si)RNA analyses were performed. Colitis was induced in mice using sodium dextran sulfate (DSS); levels of cathelicidin were measured in human primary monocytes. Results Expression of cathelicidin increased in the inflamed colonic mucosa of mice with DSS-induced colitis, compared with controls. Cathelicidin expression localized to mucosal macrophages in inflamed colon tissues of patients and mice. Exposure of human primary monocytes to E coli DNA induced expression of Camp mRNA, which required signaling by ERK; expression was reduced by siRNAs against toll-like receptor (TLR)9 and MyD88. Intracolonic administration of bacterial DNA to wild-type mice induced expression of cathelicidin in colons of control mice and mice with DSS-induced colitis. Colon expression of cathelicidin was significantly reduced in TLR9 −/− mice with DSS-induced colitis. Compared with wild-type mice, Camp −/− mice developed a more severe form of DSS-induced colitis, particularly after intracolonic administration of E coli DNA. Expression of cathelicidin from bone marrow-derived immune cells regulated DSS induction of colitis in transplantation studies in mice. Conclusions Cathelicidin protects against colitis induction in mice. Increased expression of cathelicidin in monocytes and experimental models of colitis involves activation of TLR9–ERK signaling by bacterial DNA. This pathway might be involved in pathogenesis of ulcerative colitis. PMID:21762664

Detection and characterization of murine colitis and carcinogenesis by molecularly targeted contrast-enhanced ultrasound

PubMed Central

Brückner, Markus; Heidemann, Jan; Nowacki, Tobias M; Cordes, Friederike; Stypmann, Jörg; Lenz, Philipp; Gohar, Faekah; Lügering, Andreas; Bettenworth, Dominik

2017-01-01

AIM To study mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) and vascular endothelial growth factor (VEGF)-targeted contrast enhanced ultrasound (CEUS) for the assessment of murine colitis and carcinogenesis. METHODS C57BL/6 mice were challenged with 3% dextran sodium-sulfate (DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents. MAdCAM-1-targeted contrast agent was used to detect and quantify MAdCAM-1 expression. Inflammatory driven colorectal azoxymethane (AOM)/DSS-induced carcinogenesis was examined on day 42 and 84 using VEGF-targeted contrast agent. Highly specific tissue echogenicity was quantified using specialized software. Sonographic findings were correlated to tissue staining, western blot analysis and immunohistochemistry to quantify the degree of inflammation and stage of carcinogenesis. RESULTS Native ultrasound detected increased general bowel wall thickening that correlated with more progressed and more severe DSS-colitis (healthy mice: 0.3 mm ± 0.03 vs six days DSS: 0.5 mm ± 0.2 vs nine days DSS: 0.6 mm ± 0.2, P < 0.05). Moreover, these sonographic findings correlated well with clinical parameters such as weight loss (r2 = 0.74) and histological damage (r2 = 0.86) (P < 0.01). In acute DSS-induced murine colitis, CEUS targeted against MAdCAM-1 detected and differentiated stages of mild, moderate and severe colitis via calculation of mean pixel contrast intensity in decibel (9.6 dB ± 1.6 vs 12.9 dB ± 1.4 vs 18 dB ± 3.33, P < 0.05). Employing the AOM/DSS-induced carcinogenesis model, tumor development was monitored by CEUS targeted against VEGF and detected a significantly increased echogenicity in tumors as compared to adjacent healthy mucosa (healthy mucosa, 1.6 dB ± 1.4 vs 42 d, 18.2 dB ± 3.3 vs 84 d, 18.6 dB ± 4.9, P < 0.01). Tissue echogenicity strongly correlated with histological analysis and immunohistochemistry findings (VEGF-positive cells in 10 high power fields of healthy mucosa: 1 ± 1.2 vs 42 d after DSS start: 2.4 ± 1.6 vs 84 d after DSS start: 3.5 ± 1.3, P < 0.01). CONCLUSION Molecularly targeted CEUS is a highly specific and non-invasive imaging modality, which characterizes murine intestinal inflammation and carcinogenesis in vivo. PMID:28522908

Detection and characterization of murine colitis and carcinogenesis by molecularly targeted contrast-enhanced ultrasound.

PubMed

Brückner, Markus; Heidemann, Jan; Nowacki, Tobias M; Cordes, Friederike; Stypmann, Jörg; Lenz, Philipp; Gohar, Faekah; Lügering, Andreas; Bettenworth, Dominik

2017-04-28

To study mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) and vascular endothelial growth factor (VEGF)-targeted contrast enhanced ultrasound (CEUS) for the assessment of murine colitis and carcinogenesis. C57BL/6 mice were challenged with 3% dextran sodium-sulfate (DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents. MAdCAM-1-targeted contrast agent was used to detect and quantify MAdCAM-1 expression. Inflammatory driven colorectal azoxymethane (AOM)/DSS-induced carcinogenesis was examined on day 42 and 84 using VEGF-targeted contrast agent. Highly specific tissue echogenicity was quantified using specialized software. Sonographic findings were correlated to tissue staining, western blot analysis and immunohistochemistry to quantify the degree of inflammation and stage of carcinogenesis. Native ultrasound detected increased general bowel wall thickening that correlated with more progressed and more severe DSS-colitis (healthy mice: 0.3 mm ± 0.03 vs six days DSS: 0.5 mm ± 0.2 vs nine days DSS: 0.6 mm ± 0.2, P < 0.05). Moreover, these sonographic findings correlated well with clinical parameters such as weight loss ( r 2 = 0.74) and histological damage ( r 2 = 0.86) ( P < 0.01). In acute DSS-induced murine colitis, CEUS targeted against MAdCAM-1 detected and differentiated stages of mild, moderate and severe colitis via calculation of mean pixel contrast intensity in decibel (9.6 dB ± 1.6 vs 12.9 dB ± 1.4 vs 18 dB ± 3.33, P < 0.05). Employing the AOM/DSS-induced carcinogenesis model, tumor development was monitored by CEUS targeted against VEGF and detected a significantly increased echogenicity in tumors as compared to adjacent healthy mucosa (healthy mucosa, 1.6 dB ± 1.4 vs 42 d, 18.2 dB ± 3.3 vs 84 d, 18.6 dB ± 4.9, P < 0.01). Tissue echogenicity strongly correlated with histological analysis and immunohistochemistry findings (VEGF-positive cells in 10 high power fields of healthy mucosa: 1 ± 1.2 vs 42 d after DSS start: 2.4 ± 1.6 vs 84 d after DSS start: 3.5 ± 1.3, P < 0.01). Molecularly targeted CEUS is a highly specific and non-invasive imaging modality, which characterizes murine intestinal inflammation and carcinogenesis in vivo .

Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

PubMed

Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

2015-10-10

Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of cyclodextrin complexation of curcumin on its solubility and antiangiogenic and anti-inflammatory activity in rat colitis model.

PubMed

Yadav, Vivek R; Suresh, Sarasija; Devi, Kshama; Yadav, Seema

2009-01-01

The purpose of the study was to prepare and evaluate the anti-inflammatory activity of cyclodextrin (CD) complex of curcumin for the treatment of inflammatory bowel disease (IBD) in colitis-induced rat model. Inclusion complexes of curcumin were prepared by common solvent and kneading methods. These complexes were further evaluated for increase in solubility of poorly soluble curcumin. The inclusion complexes were characterized for enhancement in solubility, in vitro dissolution, surface morphology, infrared, differential scanning calorimetry, and X-ray studies. Solubility, phase solubility, and in vitro dissolution studies showed that curcumin has higher affinity for hydroxypropyl-beta-CD (HPbetaCD) than other CDs. HPbetaCD complex of curcumin was further investigated for its antiangiogenic and anti-inflammatory activity using chick embryo and rat colitis model. HPbetaCD complex of curcumin proved to be a potent angioinhibitory compound, as demonstrated by inhibition of angiogenesis in chorioallantoic membrane assay. Curcumin- and HPbetaCD-treated rats showed a faster weight gain compared to dextran sulfate solution (DSS) controls. Whole colon length appeared to be significantly longer in HPbetaCD-treated rats than pure curcumin and DSS controls. An additional finding in the DSS-treated rats was the predominance of eosinophils in the chronic cell infiltrate. Decreased mast cell numbers in the mucosa of the colon of CD of curcumin- and pure-curcumin-treated rats was observed. This study concluded that the degree of colitis caused by administration of DSS was significantly attenuated by CD of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for IBD patients.

FGF2 cooperates with IL-17 to promote autoimmune inflammation.

PubMed

Shao, Xinrui; Chen, Siyuan; Yang, Daping; Cao, Mengtao; Yao, Yikun; Wu, Zhengxi; Li, Ningli; Shen, Nan; Li, Xiaoxia; Song, Xinyang; Qian, Youcun

2017-08-01

IL-17 is a pro-inflammatory cytokine implicated a variety of autoimmune diseases. We have recently reported that FGF2 cooperates with IL-17 to protect intestinal epithelium during dextran sodium sulfate (DSS)-induced colitis. Here, we report a pathogenic role of the FGF2-IL-17 cooperation in the pathogenesis of autoimmune arthritis. Combined treatment with FGF2 and IL-17 synergistically induced ERK activation as well as the production of cytokines and chemokines in human synovial intimal resident fibroblast-like synoviocytes (FLS). Furthermore, ectopic expression of FGF2 in mouse joints potentiated IL-17-induced inflammatory cytokine and chemokine production in the tissue. In the collagen-induced arthritis (CIA) model, while ectopic expression of FGF2 in vivo exacerbated tissue inflammation and disease symptom in the wild-type controls, the effect was largely blunted in Il17a -/- mice. Taken together, our study suggests that FGF2 cooperates with IL-17 to promote the pathogenesis of autoimmune arthritis by cooperating with IL-17 to induce inflammatory response.

Evaluation of semiautonomous navigation assistance system for power wheelchairs with blindfolded nondisabled individuals.

PubMed

Sharma, Vinod; Simpson, Richard; Lopresti, Edmund; Schmeler, Mark

2010-01-01

Some individuals with disabilities are denied powered mobility because they lack the visual, motor, and/or cognitive skills required to safely operate a power wheelchair. The Drive-Safe System (DSS) is an add-on, distributed, shared-control navigation assistance system for power wheelchairs intended to provide safe and independent mobility to such individuals. The DSS is a human-machine system in which the user is responsible for high-level control of the wheelchair, such as choosing the destination, path planning, and basic navigation actions, while the DSS overrides unsafe maneuvers through autonomous collision avoidance, wall following, and door crossing. In this project, the DSS was clinically evaluated in a controlled laboratory with blindfolded, nondisabled individuals. Further, these individuals' performance with the DSS was compared with standard cane use for navigation assistance by people with visual impairments. Results indicate that compared with a cane, the DSS significantly reduced the number of collisions. Users rated the DSS favorably even though they took longer to navigate the same obstacle course than they would have using a standard long cane. Participants experienced less physical demand, effort, and frustration when using the DSS as compared with a cane. These findings suggest that the DSS can be a viable powered mobility solution for wheelchair users with visual impairments.

Intra- and interregional cortical interactions related to sharp-wave ripples and dentate spikes.

PubMed

Headley, Drew B; Kanta, Vasiliki; Paré, Denis

2017-02-01

The hippocampus generates population events termed sharp-wave ripples (SWRs) and dentate spikes (DSs). While little is known about DSs, SWR-related hippocampal discharges during sleep are thought to replay prior waking activity, reactivating the cortical networks that encoded the initial experience. During slow-wave sleep, such reactivations likely occur during up-states, when most cortical neurons are depolarized. However, most studies have examined the relationship between SWRs and up-states measured in single neocortical regions. As a result, it is currently unclear whether SWRs are associated with particular patterns of widely distributed cortical activity. Additionally, no such investigation has been carried out for DSs. The present study addressed these questions by recording SWRs and DSs from the dorsal hippocampus simultaneously with prefrontal, sensory (visual and auditory), perirhinal, and entorhinal cortices in naturally sleeping rats. We found that SWRs and DSs were associated with up-states in all cortical regions. Up-states coinciding with DSs and SWRs exhibited increased unit activity, power in the gamma band, and intraregional gamma coherence. Unexpectedly, interregional gamma coherence rose much more strongly in relation to DSs than to SWRs. Whereas the increase in gamma coherence was time locked to DSs, that seen in relation to SWRs was not. These observations suggest that SWRs are related to the strength of up-state activation within individual regions throughout the neocortex but not so much to gamma coherence between different regions. Perhaps more importantly, DSs coincided with stronger periods of interregional gamma coherence, suggesting that they play a more important role than previously assumed. Off-line cortico-hippocampal interactions are thought to support memory consolidation. We surveyed the relationship between hippocampal sharp-wave ripples (SWRs) and dentate spikes (DSs) with up-states across multiple cortical regions. SWRs and DSs were associated with increased cortical gamma oscillations. Interregional gamma coherence rose much more strongly in relation to DSs than to SWRs. Moreover, it was time locked to DSs but not SWRs. These results have important implications for current theories of systems memory consolidation during sleep. Copyright © 2017 the American Physiological Society.

Development of a new outcome prediction model for Chinese patients with penile squamous cell carcinoma based on preoperative serum C-reactive protein, body mass index, and standard pathological risk factors: the TNCB score group system.

PubMed

Li, Zai-Shang; Chen, Peng; Yao, Kai; Wang, Bin; Li, Jing; Mi, Qi-Wu; Chen, Xiao-Feng; Zhao, Qi; Li, Yong-Hong; Chen, Jie-Ping; Deng, Chuang-Zhong; Ye, Yun-Lin; Zhong, Ming-Zhu; Liu, Zhuo-Wei; Qin, Zi-Ke; Lin, Xiang-Tian; Liang, Wei-Cong; Han, Hui; Zhou, Fang-Jian

2016-04-12

To determine the predictive value and feasibility of the new outcome prediction model for Chinese patients with penile squamous cell carcinoma. The 3-year disease-specific survival (DSS) survival (DSS) was 92.3% in patients with < 8.70 mg/L CRP and 54.9% in those with elevated CRP (P < 0.001). The 3-year DSS was 86.5% in patients with a BMI < 22.6 Kg/m2 and 69.9% in those with a higher BMI (P = 0.025). In a multivariate analysis, pathological T stage (P < 0.001), pathological N stage (P = 0.002), BMI (P = 0.002), and CRP (P = 0.004) were independent predictors of DSS. A new scoring model was developed, consisting of BMI, CRP, and tumor T and N classification. In our study, we found that the addition of the above-mentioned parameters significantly increased the predictive accuracy of the system of the American Joint Committee on Cancer (AJCC) anatomic stage group. The accuracy of the new prediction category was verified. A total of 172 Chinese patients with penile squamous cell cancer were analyzed retrospectively between November 2005 and November 2014. Statistical data analysis was conducted using the nonparametric method. Survival analysis was performed with the log-rank test and the Cox proportional hazard model. Based on regression estimates of significant parameters in multivariate analysis, a new BMI-, CRP- and pathologic factors-based scoring model was developed to predict disease--specific outcomes. The predictive accuracy of the model was evaluated using the internal and external validation. The present study demonstrated that the TNCB score group system maybe a precise and easy to use tool for predicting outcomes in Chinese penile squamous cell carcinoma patients.

LandCaRe-DSS - model based tools for irrigation management under climate change

NASA Astrophysics Data System (ADS)

Dotterweich, Markus; Wilkinson, Kristina; Cassel, Martin; Scherzer, Jörg; Köstner, Barbara; Berg, Michael; Grocholl, Jürgen

2015-04-01

Climate change is expected to have a strong influence on agricultural systems in the future. It will be important for decision makers and stakeholders to assess the impact of climate change at the farm and regional level in order to facilitate and maintain a sustainable and profitable farming infrastructure. Climate change impact studies have to incorporate aspects of uncertainty and the underlying knowledge is constantly expanding and improving. Decision support systems (DSS) with flexible data bases are therefore a useful tool for management and planning: different models can be applied under varying boundary conditions within a conceptual framework and the results can be used e.g. to show the effects of climate change scenarios and different land management options. Within this project, the already existing LandCaRe DSS will be further enhanced and improved. A first prototype had been developed for two regions in eastern Germany, mainly to show the effects of climate change on yields, nutrient balances and farm economy. The new model version will be tested and applied for a region in north-western Germany (Landkreis Uelzen) where arable land makes up about 50% of overall land-use and where 80 % of the arable land is already irrigated. For local decision makers, it will be important to know how water demand and water availability are likely to change in the future: Is more water needed for irrigation? Is more water actually available for irrigation? Will the existing limits for ground water withdrawal be sufficient for farmers to irrigate their crops? How can the irrigation water demand be influenced by land management options like the use of different crops and varieties or different farming and irrigation techniques? The main tasks of the project are (I) the integration of an improved irrigation model, (II) the development of a standardized interface to apply the DSS in different regions, (III) to optimize the graphical user interface, (IV) to transfer and apply the DSS in an example region in north-west Germany and (V) to expand the underlying data base of climate change models and scenarios. The project is funded by the Bundesministeriums für Bildung und Forschung (BMBF), Förderkennzeichen Förderkennzeichen: 02WQ1304.

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

PubMed

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

2017-06-01

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

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

PubMed

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

2015-04-01

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

Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice

PubMed Central

Li, Weidong; Hua, Baojin; Saud, Shakir M.; Lin, Hongsheng; Hou, Wei; Matter, Matthias S.; Jia, Libin; Colburn, Nancy H.; Young, Matthew R.

2015-01-01

Colorectal cancer, a leading cause of cancer death, has been linked to inflammation and obesity. Berberine, an isoquinoline alkaloid, possesses anti-inflammatory, anti-diabetes and anti-tumor properties. In the azoxymethane initiated and dextran sulfate sodium (AOM/DSS) promoted colorectal carcinogenesis mouse model, berberine treated mice showed a 60% reduction in tumor number (P=0.009), a 48% reduction in tumors <2 mm, (P=0.05); 94% reduction in tumors 2-4 mm, (P=0.001) and 100% reduction in tumors >4 mm (P=0.02) compared to vehicle treated mice. Berberine also decreased AOM/DSS induced Ki-67 and COX-2 expression. In vitro analysis showed that in addition to its anti-proliferation activity, berberine also induced apoptosis in colorectal cancer cell lines. Berberine activated AMP-activated protein kinase (AMPK), a major regulator of metabolic pathways, and inhibited mammalian target of rapamycin (mTOR), a downstream target of AMPK. Furthermore, 4E-binding protein-1 and p70 ribosomal S6 kinases, downstream targets of mTOR, were down regulated by berberine treatment. Berberine did not affect Liver kinase B1 (LKB1) activity or the mitogen-activated protein kinase pathway. Berberine inhibited Nuclear Factor kappa-B (NF-κB) activity, reduced the expression of cyclin D1 and survivin, induced phosphorylation of p53 and increased caspase-3 cleavage in vitro. Berberine inhibition of mTOR activity and p53 phosphorylation was found to be AMPK dependent, while inhibition NF-κB was AMPK independent. In vivo, berberine also activated AMPK, inhibited mTOR and p65 phosphorylation and activated caspase-3 cleavage. Our data suggests that berberine suppresses colon epithelial proliferation and tumorigenesis via AMPK dependent inhibition of mTOR activity and AMPK independent inhibition of NF-κB. PMID:24838344

Prophylactic effects of Lonicera japonica extract on dextran sulphate sodium-induced colitis in a mouse model by the inhibition of the Th1/Th17 response.

PubMed

Park, Jae-Woo; Bae, Hyunsu; Lee, Gihyun; Hong, Beom-Gi; Yoo, Hye Hyun; Lim, Sung-Jig; Lee, Kyungjin; Kim, Jinsung; Ryu, Bongha; Lee, Beom-Joon; Bae, Jinhyun; Lee, Hyejung; Bu, Youngmin

2013-01-28

Inflammatory bowel diseases (IBD) are chronically relapsing inflammatory disorders of the intestine. Although some therapeutic agents, including steroids, are available for the treatment of IBD, these agents have limited use. Therefore, dietary supplements have emerged as possible interventions for IBD. Japanese honeysuckle flower, the flower of Lonicera japonica, is a well-known dietary supplement and has been used to prevent or treat various inflammatory diseases. In the present study, we investigated the effects of L. japonica on experimental murine colitis. Colitis was induced by 5 % dextran sulphate sodium (DSS) in Balb/c mice. The water extract of L. japonica (LJE) at doses of 20, 100 or 500 mg/kg was orally administered to mice twice per day for 7 d. Body weight, colon length and a histological damage score were assessed to determine the effects on colitis. Cytokine profiles were assessed to examine the effects on helper T (Th) cell-related immunological responses. In addition, CD4⁺CD25⁺Foxp3⁺T cells were analysed in vivo and in vitro for investigating the effects on regulatory T (Treg) cells. LJE showed dose-dependent inhibitory effects against colon shortening, weight loss and histological damage. LJE down-regulated IL-1β, TNF-α, interferon-γ, IL-6, IL-12 and IL-17. However, LJE did not show any significant effects on IL-10, IL-23, transforming growth factor-β1 and Treg cell populations. In conclusion, LJE showed protective effects against DSS-induced colitis via the Th1/Th17 pathway and not via Treg cell-related mechanisms.

Swimming attenuates inflammation, oxidative stress, and apoptosis in a rat model of dextran sulfate sodium-induced chronic colitis.

PubMed

Qin, Ling; Yao, Zhi-Qiang; Chang, Qi; Zhao, Ya-Li; Liu, Ning-Ning; Zhu, Xiao-Shan; Liu, Qin-Qin; Wang, Li-Feng; Yang, An-Gang; Gao, Chun-Fang; Li, Jun-Tang

2017-01-31

Increasing evidence suggests that regular physical exercise suppresses chronic inflammation. However, the potential inhibitory effects of swimming on dextran sulfate sodium (DSS)-induced chronic colitis, and its underlying mechanisms, remain unclear. In this study, rats were orally administered DSS to induce chronic colitis, and subsequently treated with or without swimming exercise. A 7-week swimming program (1 or 1.5 hours per day, 5 days per week) ameliorated DSS-caused colon shortening, colon barrier disruption, spleen enlargement, serum LDH release, and reduction of body weight gain. Swimming for 1.5 hours per day afforded greater protection than 1 hour per day. Swimming ameliorated DSS-induced decrease in crypt depth, and increases in myeloperoxidase activity, infiltration of Ly6G+ neutrophils and TNF-α- and IFN-γ-expressing CD3+ T cells, as well as fecal calprotectin and lactoferrin. Swimming inhibited pro-inflammatory cytokine and chemokine production and decreased the protein expression of phosphorylated nuclear factor-κB p65 and cyclooxygenase 2, whereas it elevated interleukin-10 levels. Swimming impeded the generation of reactive oxygen species, malondialdehyde, and nitric oxide; however, it boosted glutathione levels, total antioxidant capacity, and superoxide dismutase and glutathione peroxidase activities. Additionally, swimming decreased caspase-3 activity and expression of apoptosis-inducing factor, cytochrome c, Bax, and cleaved-caspase-3, but increased Bcl-2 levels. Overall, these results suggest that swimming exerts beneficial effects on DSS-induced chronic colitis by modulating inflammation, oxidative stress, and apoptosis.

Swimming attenuates inflammation, oxidative stress, and apoptosis in a rat model of dextran sulfate sodium-induced chronic colitis

PubMed Central

Zhu, Xiao-shan; Liu, Qin-qin; Wang, Li-feng; Yang, An-gang; Gao, Chun-fang; Li, Jun-tang

2017-01-01

Increasing evidence suggests that regular physical exercise suppresses chronic inflammation. However, the potential inhibitory effects of swimming on dextran sulfate sodium (DSS)-induced chronic colitis, and its underlying mechanisms, remain unclear. In this study, rats were orally administered DSS to induce chronic colitis, and subsequently treated with or without swimming exercise. A 7-week swimming program (1 or 1.5 hours per day, 5 days per week) ameliorated DSS-caused colon shortening, colon barrier disruption, spleen enlargement, serum LDH release, and reduction of body weight gain. Swimming for 1.5 hours per day afforded greater protection than 1 hour per day. Swimming ameliorated DSS-induced decrease in crypt depth, and increases in myeloperoxidase activity, infiltration of Ly6G+ neutrophils and TNF-a- and IFN-?-expressing CD3+ T cells, as well as fecal calprotectin and lactoferrin. Swimming inhibited pro-inflammatory cytokine and chemokine production and decreased the protein expression of phosphorylated nuclear factor-?B p65 and cyclooxygenase 2, whereas it elevated interleukin-10 levels. Swimming impeded the generation of reactive oxygen species, malondialdehyde, and nitric oxide; however, it boosted glutathione levels, total antioxidant capacity, and superoxide dismutase and glutathione peroxidase activities. Additionally, swimming decreased caspase-3 activity and expression of apoptosis-inducing factor, cytochrome c, Bax, and cleaved-caspase-3, but increased Bcl-2 levels. Overall, these results suggest that swimming exerts beneficial effects on DSS-induced chronic colitis by modulating inflammation, oxidative stress, and apoptosis. PMID:28030847

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, T.-Y.; Division of Gastroenterology and Hepatology, Tri-Service General Hospital, Taipei, Taiwan; Chu, H.-C.

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 nitricmore » 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.« less

Suppression of dextran sulfate sodium-induced colitis in mice by radon inhalation.

PubMed

Nishiyama, Yuichi; Kataoka, Takahiro; Yamato, Keiko; Taguchi, Takehito; Yamaoka, Kiyonori

2012-01-01

The enhanced release of reactive oxygen species from activated neutrophils plays important role in the pathogenesis of inflammatory bowel disease. We previously reported that radon inhalation activates antioxidative functions in various organs of mice. In this study, we examined the protective effects of radon inhalation on dextran sulfate sodium- (DSS) induced colitis in mice which were subjected to DSS for 7 days. Mice were continuously treated with air only (sham) or radon at a concentration of 2000 Bq/m³ from a day before DSS administration to the end of colitis induction. In the results, radon inhalation suppressed the elevation of the disease activity index score and histological damage score induced by DSS. Based on the changes in tumor necrosis factor-alpha in plasma and myeloperoxidase activity in the colon, it was shown that radon inhalation suppressed DSS-induced colonic inflammation. Moreover, radon inhalation suppressed lipid peroxidation of the colon induced by DSS. The antioxidant level (superoxide dismutase and total glutathione) in the colon after DSS administration was significantly higher in mice treated with radon than with the sham. These results suggested that radon inhalation suppressed DSS-induced colitis through the enhancement of antioxidative functions in the colon.

Suppression of Dextran Sulfate Sodium-Induced Colitis in Mice by Radon Inhalation

PubMed Central

Nishiyama, Yuichi; Kataoka, Takahiro; Yamato, Keiko; Taguchi, Takehito; Yamaoka, Kiyonori

2012-01-01

The enhanced release of reactive oxygen species from activated neutrophils plays important role in the pathogenesis of inflammatory bowel disease. We previously reported that radon inhalation activates antioxidative functions in various organs of mice. In this study, we examined the protective effects of radon inhalation on dextran sulfate sodium- (DSS) induced colitis in mice which were subjected to DSS for 7 days. Mice were continuously treated with air only (sham) or radon at a concentration of 2000 Bq/m3 from a day before DSS administration to the end of colitis induction. In the results, radon inhalation suppressed the elevation of the disease activity index score and histological damage score induced by DSS. Based on the changes in tumor necrosis factor-alpha in plasma and myeloperoxidase activity in the colon, it was shown that radon inhalation suppressed DSS-induced colonic inflammation. Moreover, radon inhalation suppressed lipid peroxidation of the colon induced by DSS. The antioxidant level (superoxide dismutase and total glutathione) in the colon after DSS administration was significantly higher in mice treated with radon than with the sham. These results suggested that radon inhalation suppressed DSS-induced colitis through the enhancement of antioxidative functions in the colon. PMID:23365486

Anti-Inflammatory Effects of Ethanol Extract of Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), in Mice with Ulcerative Colitis.

PubMed

Qin, Mingming; Geng, Yan; Lu, Zhenming; Xu, Hongyu; Shi, Jin-Song; Xu, Xin; Xu, Zheng-Hong

2016-01-01

This study investigated the anti-inflammatory activity of ethanol extracts of Hericium erinaceus in the inflammatory bowel disease (IBD) model. Twenty C57BL/6 mice were exposed to 2% (w/v) dextran sulfate sodium (DSS) in their drinking water for 7 d to induce acute intestinal inflammation. Orally administrated ethanol extract of H. erinaceus (HEEE) (250 mg/kg/d and 500 mg/kg/d body weight) could significantly (P < 0.05) improve body weight and colon length and decreased the intestinal bleeding of DSS-treated mice compared with DSS-treated mice not given HEEE. HEEE markedly reduced DSS-induced myeloperoxidase accumulation in colon tissues, attenuated histological change in the neutrophils and lymphocyte infiltration, and protected the mucosal epithelium. Mechanistically, HEEE ameliorated colitis not only by suppressing the production of inflammatory mediators including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in colon tissues but also by adjusting the production of nitric oxide, malondialdehyde, and superoxide dismutase in serum to suppress the oxidative stress. These results suggest that HEEE can be applied as a protective agent in the treatment of IBDs.

Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism

PubMed Central

Yan, Fang; Cao, Hanwei; Cover, Timothy L.; Washington, M. Kay; Shi, Yan; Liu, LinShu; Chaturvedi, Rupesh; Peek, Richard M.; Wilson, Keith T.; Polk, D. Brent

2011-01-01

Probiotic bacteria can potentially have beneficial effects on the clinical course of several intestinal disorders, but our understanding of probiotic action is limited. We have identified a probiotic bacteria–derived soluble protein, p40, from Lactobacillus rhamnosus GG (LGG), which prevents cytokine-induced apoptosis in intestinal epithelial cells. In the current study, we analyzed the mechanisms by which p40 regulates cellular responses in intestinal epithelial cells and p40’s effects on experimental colitis using mouse models. We show that the recombinant p40 protein activated EGFR, leading to Akt activation. Activation of EGFR by p40 was required for inhibition of cytokine-induced apoptosis in intestinal epithelial cells in vitro and ex vivo. Furthermore, we developed a pectin/zein hydrogel bead system to specifically deliver p40 to the mouse colon, which activated EGFR in colon epithelial cells. Administration of p40-containing beads reduced intestinal epithelial apoptosis and disruption of barrier function in the colon epithelium in an EGFR-dependent manner, thereby preventing and treating DSS-induced intestinal injury and acute colitis. Furthermore, p40 activation of EGFR was required for ameliorating colon epithelial cell apoptosis and chronic inflammation in oxazolone-induced colitis. These data define what we believe to be a previously unrecognized mechanism of probiotic-derived soluble proteins in protecting the intestine from injury and inflammation. PMID:21606592

Preclinical Development of a Novel, Orally-Administered Anti-Tumour Necrosis Factor Domain Antibody for the Treatment of Inflammatory Bowel Disease.

PubMed

Crowe, J Scott; Roberts, Kevin J; Carlton, Timothy M; Maggiore, Luana; Cubitt, Marion F; Clare, Simon; Harcourt, Katherine; Reckless, Jill; MacDonald, Thomas T; Ray, Keith P; Vossenkämper, Anna; West, Michael R

2018-03-21

TNFα is an important cytokine in inflammatory bowel disease. V565 is a novel anti-TNFα domain antibody developed for oral administration in IBD patients, derived from a llama domain antibody and engineered to enhance intestinal protease resistance. V565 activity was evaluated in TNFα-TNFα receptor-binding ELISAs as well as TNFα responsive cellular assays and demonstrated neutralisation of both soluble and membrane TNFα with potencies similar to those of adalimumab. Although sensitive to pepsin, V565 retained activity after lengthy incubations with trypsin, chymotrypsin, and pancreatin, as well as mouse small intestinal and human ileal and faecal supernatants. In orally dosed naïve and DSS colitis mice, high V565 concentrations were observed in intestinal contents and faeces and immunostaining revealed V565 localisation in mouse colon tissue. V565 was detected by ELISA in post-dose serum of colitis mice, but not naïve mice, demonstrating penetration of disrupted epithelium. In an ex vivo human IBD tissue culture model, V565 inhibition of tissue phosphoprotein levels and production of inflammatory cytokine biomarkers was similar to infliximab, demonstrating efficacy when present at the disease site. Taken together, results of these studies provide confidence that oral V565 dosing will be therapeutic in IBD patients where the mucosal epithelial barrier is compromised.

Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org; Vance, Sean; Suri, Jaipreet S.

2014-02-01

Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years.more » All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma. Furthermore, adjuvant RT is an independent predictor for RFS, DSS, and OS in this group of patients. These findings need validation from a prospective randomized study.« less

Screening of the optimized prescription from Suqingwan in terms of its therapeutic effect on DSS-induced ulcerative colitis by its regulation of inflammatory and oxidative mediators.

PubMed

Shao, Jingxuan; Liu, Zhihui; Wang, Lin; Song, Zehai; Chang, Hang; Han, Na; Yin, Jun

2017-04-18

Suqingwan (SQW), a traditional Chinese medicine used for treating ulcerative colitis (UC), is composed of 13 kinds of Traditional Chinese medicines (TCMs). According to TCM theory, we investigated whether a simplified prescription composed of the herbs with some functions, would have similar effects to SQW and examined its potential treatment mechanism of action. We categorized the herbs in SQW into four groups according to their traditional functions and used an orthogonal experimental design to obtain nine separated prescriptions (SPs) of SQW. A dextran sulfate sodium (DSS)-induced UC mouse model was used to evaluate the anti-ulcer colitis effects of the nine SPs and the calculated prescription (CP) was obtained based on the orthogonal t values of the disease activity index (DAI) of the nine SPs. The effect of the CP and SP8 were verified in the DSS-induced UC model, and the DAI and histopathology of the UC mice were examined. Myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4 and IL-10 of the mice in SP8 were investigated to explore the mechanism of action of the optimized prescription with regard to anti-inflammatory and anti-oxidation effects. Among the 9 SPs, separate prescription 6, 7 and 8 (SP6, SP7 and SP8) and the SQW formulation all significantly reduced the DAI of the UC mice and, in particular, SP8 had an effect similar to SQW, which consists of Sanguisorba officinalis L., Rehmannia glutinosa Libosch. and four other herbal medicines. In a further investigation, SP8 was found to improve the ulcerative colitis in mice in terms of both clinical symptoms and histopathology. The mortality of mice in the SP8 group was 33.3%, better than CP based on the orthogonal t values (83.3%). SP8 could also reduce the levels of TNF-α, IL-1β, IL-6, MPO and MDA and increase the levels of IL-4 and IL-10 in colon tissue of UC mice in comparison with those of the model group (p<0.05). An optimized prescription (SP8) from SQW was obtained based on an orthogonal experimental design, which involved 6 herbal medicines, with significantly fewer herbs than in the original prescription. SP8 displayed a similar anti-ulcerative colitis activity to SQW, and its in vivo mechanism of action is related to up-regulation of anti-inflammatory cytokines and down-regulation of pro-inflammatory and oxidative factors. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

A web-based spatial decision supporting system (S-DSS) for grapevine quality: the viticultural tool of the SOILCONS-WEB Project

NASA Astrophysics Data System (ADS)

Manna, Piero; Bonfante, Antonello; Basile, Angelo; Langella, Giuliano; Agrillo, Antonietta; De Mascellis, Roberto; Florindo Mileti, Antonio; Minieri, Luciana; Orefice, Nadia; Terribile, Fabio

2014-05-01

The SOILCONSWEB Project aims to create a decision support system operating at the landscape scale (Spatial-DSS) for the protection and the management of soils in both agricultural and environmental issues; it is a cyber-infrastructure built on remote servers operating through the web at www.landconsultingweb.eu. It includes - among others - a series of tools specifically designed to a Viticulture aiming at high quality wines production. The system is realized thanks to a collaboration between the University of Naples Federico II, CNR ISAFoM, Ariespace srl and SeSIRCA-Campania Region within a 5-years LIFE+ project funded by European Community. The system includes tools based on modelling procedures at different level of complexity some of which specifically designed for viticulture issues. One of the implemented models arise from the original desktop based SWAP model (Kroes et al, 2008). It can be run "on the fly" through a very user friendly web-interface. The specific tool, thanks to the model based on the Richard's equation can produce data on vineyard water stress, simulating the soil water balances of the different soil types within an area of interest. Thanks to a specific program developed within the project activities, the Spatial-DSS every day acquires punctual weather data and automatically spatialize them with geostatistical approaches in order to use the data as input for the SPA (Soil Plant Atmosphere ) model running. In particular for defining the upper boundary condition (rainfall and temperatures to estimate ET0 by the Hargraves model). Soil hydraulic properties (47 soil profiles within the study area), also essential for modelling simulation, were measured in laboratory using the Wind's approach or estimated through HYPRES PTF. Water retention and hydraulic conductivity relationships were parameterized according to the van Genuchten-Mualem model; Decision makers (individuals, groups of interests and public bodies) through the DSS can have real-time (or near real-time) access to critical, accurate, complete and up-to-date spatial data/output models held/processed in multiple data stores. The system allows the users interested in viticulture to have free, easy and immediate access to a number of environmental data and information very useful for quality wines production and especially for viticulture planning and management in a context of environmental sustainability. It produces detailed spatial documents, report and maps on a series of questions including the identification and description of terroir characteristics. The user once connected to the S-DSS can select an area of interest (i.e. farm, municipality, district) or draw it and obtain in real time a series of detailed information regarding that specific area, including maps and reports of landscape physical factors (i.e. soils, climate, geology, geomorphology, etc.), viticulture suitability, plant disease data and modelling, trends of viticulture years, bioclimatic indexes, etc. The user can also choose between different options such as the time period of the simulation runs or the type of data (maps, report or graphs) to be produced by the system. The S-DSS is being developed, tested and applied in an area of about 20,000 ha in south of Italy (Valle Telesina, in Campania region) mainly vocated to quality wines production (designation of origin DOC and DOCG). Key words: Decision Support System, spatial data, model simulation, soil hydrological properties, cyber infrastructure.

A Web-Based Decision Support System for Assessing Regional Water-Quality Conditions and Management Actions

NASA Astrophysics Data System (ADS)

Booth, N. L.; Everman, E.; Kuo, I.; Sprague, L.; Murphy, L.

2011-12-01

A new web-based decision support system has been developed as part of the U.S. Geological Survey (USGS) National Water Quality Assessment Program's (NAWQA) effort to provide ready access to Spatially Referenced Regressions On Watershed attributes (SPARROW) results of stream water-quality conditions and to offer sophisticated scenario testing capabilities for research and water-quality planning via an intuitive graphical user interface with a map-based display. The SPARROW Decision Support System (DSS) is delivered through a web browser over an Internet connection, making it widely accessible to the public in a format that allows users to easily display water-quality conditions, distribution of nutrient sources, nutrient delivery to downstream waterbodies, and simulations of altered nutrient inputs including atmospheric and agricultural sources. The DSS offers other features for analysis including various background map layers, model output exports, and the ability to save and share prediction scenarios. SPARROW models currently supported by the DSS are based on the modified digital versions of the 1:500,000-scale River Reach File (RF1) and 1:100,000-scale National Hydrography Dataset (medium-resolution, NHDPlus) stream networks. The underlying modeling framework and server infrastructure illustrate innovations in the information technology and geosciences fields for delivering SPARROW model predictions over the web by performing intensive model computations and map visualizations of the predicted conditions within the stream network.

Testing alternative ground water models using cross-validation and other methods

USGS Publications Warehouse

Foglia, L.; Mehl, S.W.; Hill, M.C.; Perona, P.; Burlando, P.

2007-01-01

Many methods can be used to test alternative ground water models. Of concern in this work are methods able to (1) rank alternative models (also called model discrimination) and (2) identify observations important to parameter estimates and predictions (equivalent to the purpose served by some types of sensitivity analysis). Some of the measures investigated are computationally efficient; others are computationally demanding. The latter are generally needed to account for model nonlinearity. The efficient model discrimination methods investigated include the information criteria: the corrected Akaike information criterion, Bayesian information criterion, and generalized cross-validation. The efficient sensitivity analysis measures used are dimensionless scaled sensitivity (DSS), composite scaled sensitivity, and parameter correlation coefficient (PCC); the other statistics are DFBETAS, Cook's D, and observation-prediction statistic. Acronyms are explained in the introduction. Cross-validation (CV) is a computationally intensive nonlinear method that is used for both model discrimination and sensitivity analysis. The methods are tested using up to five alternative parsimoniously constructed models of the ground water system of the Maggia Valley in southern Switzerland. The alternative models differ in their representation of hydraulic conductivity. A new method for graphically representing CV and sensitivity analysis results for complex models is presented and used to evaluate the utility of the efficient statistics. The results indicate that for model selection, the information criteria produce similar results at much smaller computational cost than CV. For identifying important observations, the only obviously inferior linear measure is DSS; the poor performance was expected because DSS does not include the effects of parameter correlation and PCC reveals large parameter correlations. ?? 2007 National Ground Water Association.

mHealth App for iOS to Help in Diagnostic Decision in Ophthalmology to Primary Care Physicians.

PubMed

López, Marta Manovel; López, Miguel Maldonado; de la Torre Díez, Isabel; Jimeno, José Carlos Pastor; López-Coronado, Miguel

2017-05-01

Decision support systems (DSS) are increasingly demanded due that diagnosis is one of the main activities that physicians accomplish every day. This fact seems critical when primary care physicians deal with uncommon problems belonging to specialized areas. The main objective of this paper is the development and user evaluation of a mobile DSS for iOS named OphthalDSS. This app has as purpose helping in anterior segment ocular diseases' diagnosis, besides offering educative content about ophthalmic diseases to users. For the deployment of this work, firstly it has been used the Apple IDE, Xcode, to develop the OphthalDSS mobile application using Objective-C as programming language. The core of the decision support system implemented by OphthalDSS is a decision tree developed by expert ophthalmologists. In order to evaluate the Quality of Experience (QoE) of primary care physicians after having tried the OphthalDSS app, a written inquiry based on the Likert scale was used. A total of 50 physicians answered to it, after trying the app during 1 month in their medical consultation. OphthalDSS is capable of helping to make diagnoses of diseases related to the anterior segment of the eye. Other features of OphthalDSS are a guide of each disease and an educational section. A 70% of the physicians answered in the survey that OphthalDSS performs in the way that they expected, and a 95% assures their trust in the reliability of the clinical information. Moreover, a 75% of them think that the decision system has a proper performance. Most of the primary care physicians agree with that OphthalDSS does the function that they expected, it is a user-friendly and the contents and structure are adequate. We can conclude that OphthalDSS is a practical tool but physicians require extra content that makes it a really useful one.

Evaluation of Gastrointestinal Leakage in Multiple Enteric Inflammation Models in Chickens.

PubMed

Kuttappan, Vivek A; Vicuña, Eduardo A; Latorre, Juan D; Wolfenden, Amanda D; Téllez, Guillermo I; Hargis, Billy M; Bielke, Lisa R

2015-01-01

Enteric inflammation models can help researchers' study methods to improve health and performance and evaluate various growth promoters and dietary formulations targeted to improve performance in poultry. Oral administration of fluorescein isothiocyanate-dextran (FITC-d; 3-5 kDa) and its pericellular mucosal epithelial leakage are an established marker to evaluate enteric inflammation in multiple species. The present study evaluated different methods to induce gut inflammation in poultry based on FITC-d leakage. Four independent experiments were completed with different inflammation treatment groups, and serum FITC-d and/or retention of FITC-d in GI tract were determined. In experiment 1 (n = 10 birds/treatment, broilers, processed at 14 days), groups included control (CON), dextran sodium sulfate (DSS; drinking water at 0.75%) and feed restriction (FRS; 24 h before processing). Experiment 2 (n = 14 birds/treatment, leghorns, processed at 7 days) included CON, DSS, FRS, and rye-based diet (RBD). In experiments 3 and 4 (n = 15 birds/treatment, broilers, processed at 7 days), groups were CON, DSS, high fat diet (HFD), FRS, and RBD. In all experiments, FRS and RBD treatments showed significantly higher serum FITC-d levels compared to the respective CON. This indicates that FRS and RBD results in disruption of the intact barrier of the gastrointestinal tract (GIT), resulting in increased gut permeability. DSS and HFD groups showed elevation of serum FITC-d levels although the magnitude of difference from respective CON was inconsistent between experiments. FRS was the only treatment which consistently showed elevated retention of FITC-d in GIT in all experiments. The results from present studies showed that FRS and RBD, based on serum FITC-d levels, can be robust models to induce gut leakage in birds in different age and species/strains.

Assessing climate change impacts on wetlands in a flow regulated catchment: A case study in the Macquarie Marshes, Australia.

PubMed

Fu, Baihua; Pollino, Carmel A; Cuddy, Susan M; Andrews, Felix

2015-07-01

Globally wetlands are increasingly under threat due to changes in water regimes as a result of river regulation and climate change. We developed the Exploring CLimAte Impacts on Management (EXCLAIM) decision support system (DSS), which simulates flow-driven habitat condition for 16 vegetation species, 13 waterbird species and 4 fish groups in the Macquarie catchment, Australia. The EXCLAIM DSS estimates impacts to habitat condition, considering scenarios of climate change and water management. The model framework underlying the DSS is a probabilistic Bayesian network, and this approach was chosen to explicitly represent uncertainties in climate change scenarios and predicted ecological outcomes. The results suggest that the scenario with no climate change and no water resource development (i.e. flow condition without dams, weirs or water license entitlements, often regarded as a surrogate for 'natural' flow) consistently has the most beneficial outcomes for vegetation, waterbird and native fish. The 2030 dry climate change scenario delivers the poorest ecological outcomes overall, whereas the 2030 wet climate change scenario has beneficial outcomes for waterbird breeding, but delivers poor outcomes for river red gum and black box woodlands, and fish that prefer river channels as habitats. A formal evaluation of the waterbird breeding model showed that higher numbers of observed nest counts are typically associated with higher modelled average breeding habitat conditions. The EXCLAIM DSS provides a generic framework to link hydrology and ecological habitats for a large number of species, based on best available knowledge of their flood requirements. It is a starting point towards developing an integrated tool for assessing climate change impacts on wetland ecosystems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identifying Opportunities for Decision Support Systems in Support of Regional Resource Use Planning: An Approach Through Soft Systems Methodology.

PubMed

Zhu; Dale

2000-10-01

/ Regional resource use planning relies on key regional stakeholder groups using and having equitable access to appropriate social, economic, and environmental information and assessment tools. Decision support systems (DSS) can improve stakeholder access to such information and analysis tools. Regional resource use planning, however, is a complex process involving multiple issues, multiple assessment criteria, multiple stakeholders, and multiple values. There is a need for an approach to DSS development that can assist in understanding and modeling complex problem situations in regional resource use so that areas where DSSs could provide effective support can be identified, and the user requirements can be well established. This paper presents an approach based on the soft systems methodology for identifying DSS opportunities for regional resource use planning, taking the Central Highlands Region of Queensland, Australia, as a case study.

BIOCHEM-ORCHESTRA: a tool for evaluating chemical speciation and ecotoxicological impacts of heavy metals on river flood plain systems.

PubMed

Vink, J P M; Meeussen, J C L

2007-08-01

The chemical speciation model BIOCHEM was extended with ecotoxicological transfer functions for uptake of metals (As, Cd, Cu, Ni, Pb, and Zn) by plants and soil invertebrates. It was coupled to the object-oriented framework ORCHESTRA to achieve a flexible and dynamic decision support system (DSS) to analyse natural or anthropogenic changes that occur in river systems. The DSS uses the chemical characteristics of soils and sediments as input, and calculates speciation and subsequent uptake by biota at various scenarios. Biotic transfer functions were field-validated, and actual hydrological conditions were derived from long-term monitoring data. The DSS was tested for several scenarios that occur in the Meuse catchment areas, such as flooding and sedimentation of riverine sediments on flood plains. Risks are expressed in terms of changes in chemical mobility, and uptake by flood plain key species (flora and fauna).

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

A cytochrome P450, OsDSS1, is involved in growth and drought stress responses in rice (Oryza sativa L.).

PubMed

Tamiru, Muluneh; Undan, Jerwin R; Takagi, Hiroki; Abe, Akira; Yoshida, Kakoto; Undan, Jesusa Q; Natsume, Satoshi; Uemura, Aiko; Saitoh, Hiromasa; Matsumura, Hideo; Urasaki, Naoya; Yokota, Takao; Terauchi, Ryohei

2015-05-01

Cytochrome P450s are among the largest protein coding gene families in plant genomes. However, majority of the genes remain uncharacterized. Here, we report the characterization of dss1, a rice mutant showing dwarfism and reduced grain size. The dss1 phenotype is caused by a non-synonymous point mutation we identified in DSS1, which is member of a P450 gene cluster located on rice chromosome 3 and corresponds to the previously reported CYP96B4/SD37 gene. Phenotypes of several dwarf mutants characterized in rice are associated with defects in the biosynthesis or perception of the phytohormones gibberellins (GAs) and brassinosteroids (BRs). However, both GA and BR failed to rescue the dss1 phenotype. Hormone profiling revealed the accumulation of abscisic acid (ABA) and ABA metabolites, as well as significant reductions in GA19 and GA53 levels, precursors of the bioactive GA1, in the mutant. The dss1 contents of cytokinin and auxins were not significantly different from wild-type plants. Consistent with the accumulation of ABA and metabolites, germination and early growth was delayed in dss1, which also exhibited an enhanced tolerance to drought. Additionally, expressions of members of the DSS1/CYP96B gene cluster were regulated by drought stress and exogenous ABA. RNA-seq-based transcriptome profiling revealed, among others, that cell wall-related genes and genes involved in lipid metabolism were up- and down-regulated in dss1, respectively. Taken together, these findings suggest that DSS1 mediates growth and stress responses in rice by fine-tuning GA-to-ABA balance, and might as well play a role in lipid metabolism.

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

PubMed

Gobert, Alain P; Al-Greene, Nicole T; Singh, Kshipra; Coburn, Lori A; Sierra, Johanna C; Verriere, Thomas G; Luis, Paula B; Schneider, Claus; Asim, Mohammad; Allaman, Margaret M; Barry, Daniel P; Cleveland, John L; Destefano Shields, Christina E; Casero, Robert A; Washington, M Kay; Piazuelo, M Blanca; Wilson, Keith T

2018-01-01

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

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

PubMed Central

Gobert, Alain P.; Al-Greene, Nicole T.; Singh, Kshipra; Coburn, Lori A.; Sierra, Johanna C.; Verriere, Thomas G.; Luis, Paula B.; Schneider, Claus; Asim, Mohammad; Allaman, Margaret M.; Barry, Daniel P.; Cleveland, John L.; Destefano Shields, Christina E.; Casero, Robert A.; Washington, M. Kay; Piazuelo, M. Blanca; Wilson, Keith T.

2018-01-01

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

Risk prediction of Critical Infrastructures against extreme natural hazards: local and regional scale analysis

NASA Astrophysics Data System (ADS)

Rosato, Vittorio; Hounjet, Micheline; Burzel, Andreas; Di Pietro, Antonio; Tofani, Alberto; Pollino, Maurizio; Giovinazzi, Sonia

2016-04-01

Natural hazard events can induce severe impacts on the built environment; they can hit wide and densely populated areas, where there is a large number of (inter)dependent technological systems whose damages could cause the failure or malfunctioning of further different services, spreading the impacts on wider geographical areas. The EU project CIPRNet (Critical Infrastructures Preparedness and Resilience Research Network) is realizing an unprecedented Decision Support System (DSS) which enables to operationally perform risk prediction on Critical Infrastructures (CI) by predicting the occurrence of natural events (from long term weather to short nowcast predictions, correlating intrinsic vulnerabilities of CI elements with the different events' manifestation strengths, and analysing the resulting Damage Scenario. The Damage Scenario is then transformed into an Impact Scenario, where punctual CI element damages are transformed into micro (local area) or meso (regional) scale Services Outages. At the smaller scale, the DSS simulates detailed city models (where CI dependencies are explicitly accounted for) that are of important input for crisis management organizations whereas, at the regional scale by using approximate System-of-Systems model describing systemic interactions, the focus is on raising awareness. The DSS has allowed to develop a novel simulation framework for predicting earthquakes shake maps originating from a given seismic event, considering the shock wave propagation in inhomogeneous media and the subsequent produced damages by estimating building vulnerabilities on the basis of a phenomenological model [1, 2]. Moreover, in presence of areas containing river basins, when abundant precipitations are expected, the DSS solves the hydrodynamic 1D/2D models of the river basins for predicting the flux runoff and the corresponding flood dynamics. This calculation allows the estimation of the Damage Scenario and triggers the evaluation of the Impact Scenario. The regional output of cascading effects can be used as an input model for more detailed analyses within urban areas for instance. The DSS weights the overall expected Crisis Scenario by also considering, through an appropriate Consequences Analysis, the number of citizens affected by the Service(s) outages, the expected economic losses of the major industrial activities hit by the unavailability of relevant Services (electricity, water, telecommunications etc.) and the influence of outages of the availability of Public Services (hospitals, schools, public offices etc.) [1] S.Giovinazzi, S. Lagomarsino: A macroseismic method for the vulnerability assessment of buildings. 13th World Conference on Earthquake Engineering, Vancouver, BC, Canada (2004) [2] S. Lagomarsino, S.Giovinazzi: Macroseismic and mechanical models for the vulnerability and damage assessment of current buildings. Bull Earthquake Eng., 4:415-443 (2006)

A novel roseobacter phage possesses features of podoviruses, siphoviruses, prophages and gene transfer agents

PubMed Central

Zhan, Yuanchao; Huang, Sijun; Voget, Sonja; Simon, Meinhard; Chen, Feng

2016-01-01

Bacteria in the Roseobacter lineage have been studied extensively due to their significant biogeochemical roles in the marine ecosystem. However, our knowledge on bacteriophage which infects the Roseobacter clade is still very limited. Here, we report a new bacteriophage, phage DSS3Φ8, which infects marine roseobacter Ruegeria pomeroyi DSS-3. DSS3Φ8 is a lytic siphovirus. Genomic analysis showed that DSS3Φ8 is most closely related to a group of siphoviruses, CbK-like phages, which infect freshwater bacterium Caulobacter crescentus. DSS3Φ8 contains a smaller capsid and has a reduced genome size (146 kb) compared to the CbK-like phages (205–279 kb). DSS3Φ8 contains the DNA polymerase gene which is closely related to T7-like podoviruses. DSS3Φ8 also contains the integrase and repressor genes, indicating its potential to involve in lysogenic cycle. In addition, four GTA (gene transfer agent) genes were identified in the DSS3Φ8 genome. Genomic analysis suggests that DSS3Φ8 is a highly mosaic phage that inherits the genetic features from siphoviruses, podoviruses, prophages and GTAs. This is the first report of CbK-like phages infecting marine bacteria. We believe phage isolation is still a powerful tool that can lead to discovery of new phages and help interpret the overwhelming unknown sequences in the viral metagenomics. PMID:27460944

A novel roseobacter phage possesses features of podoviruses, siphoviruses, prophages and gene transfer agents

NASA Astrophysics Data System (ADS)

Zhan, Yuanchao; Huang, Sijun; Voget, Sonja; Simon, Meinhard; Chen, Feng

2016-07-01

Bacteria in the Roseobacter lineage have been studied extensively due to their significant biogeochemical roles in the marine ecosystem. However, our knowledge on bacteriophage which infects the Roseobacter clade is still very limited. Here, we report a new bacteriophage, phage DSS3Φ8, which infects marine roseobacter Ruegeria pomeroyi DSS-3. DSS3Φ8 is a lytic siphovirus. Genomic analysis showed that DSS3Φ8 is most closely related to a group of siphoviruses, CbK-like phages, which infect freshwater bacterium Caulobacter crescentus. DSS3Φ8 contains a smaller capsid and has a reduced genome size (146 kb) compared to the CbK-like phages (205-279 kb). DSS3Φ8 contains the DNA polymerase gene which is closely related to T7-like podoviruses. DSS3Φ8 also contains the integrase and repressor genes, indicating its potential to involve in lysogenic cycle. In addition, four GTA (gene transfer agent) genes were identified in the DSS3Φ8 genome. Genomic analysis suggests that DSS3Φ8 is a highly mosaic phage that inherits the genetic features from siphoviruses, podoviruses, prophages and GTAs. This is the first report of CbK-like phages infecting marine bacteria. We believe phage isolation is still a powerful tool that can lead to discovery of new phages and help interpret the overwhelming unknown sequences in the viral metagenomics.

Dietary Phenethyl Isothiocyanate Protects Mice from Colitis Associated Colon Cancer.

PubMed

Liu, Yi; Dey, Moul

2017-09-06

We have previously reported alleviation of dextran sodium sulfate (DSS)-induced ulcerative colitis signs in phenethyl isothiocyanate (PEITC)-treated mice. Here we investigated chemoprotective activities of PEITC in mice with Azoxymethane-DSS induced colitis associated colon carcinogenesis. We also examined the molecular mediators associated with the PEITC effects using relevant cell lines. A 0.12% PEITC-enriched mouse-diet reduced mucosal and submucosal inflammation as well as glandular atypia by 12% and the frequency of adenocarcinoma by 17% with a concomitant improvement in overall disease activity indices compared to the diseased control group. Lipopolysaccharide-induced in vitro up-regulation of key mediators of inflammation, immune response, apoptosis, and cell proliferation were attenuated by 10 μM PEITC. Three of these mediators showed concentration-dependent reduction in respective mRNAs. Furthermore, PEITC inhibited Nuclear factor kappa B1 (NFκB1) proteins in a concentration-dependent manner. The NFκB1 mRNA expression inversely correlated ( r = −0.940, p = 0.013) with tri-methylation of lysine 27 on histone 3 near its promoter region in a time-dependent manner. These results indicate that PEITC may slow down the development of colon carcinogenesis in an inflammatory intestinal setting which is potentially associated with epigenetic modulation of NFκB1 signaling.

An apple oligogalactan prevents against inflammation and carcinogenesis by targeting LPS/TLR4/NF-κB pathway in a mouse model of colitis-associated colon cancer.

PubMed

Liu, Li; Li, Yu H; Niu, Yin B; Sun, Yang; Guo, Zhen J; Li, Qian; Li, Chen; Feng, Juan; Cao, Shou S; Mei, Qi B

2010-10-01

Evidence strongly supported a link between inflammation and cancer. Patients with colitis have high risk for development of colon cancer. Nuclear factor-kappa B (NF-κB), partially induced by lipopolysaccharide (LPS) binding to Toll-like receptor (TLR) 4, is a vital molecule in supervising the transformation of colitis to colon cancer. It could be a good strategy to prevent colitis carcinogenesis for targeting LPS/TLR4/NF-κB pathway. In the present study, we obtained an oligogalactan composed of five galacturonic acids from apple pectin and evaluated its protective efficacy on intestinal toxicities and carcinogenesis in a mouse model of colitis-associated colon cancer induced by 1,2-dimethylhydrazine and dextran sodium sulfate (DSS). The apple oligogalactan (AOG) was highly effective against intestinal toxicities and carcinogenesis and decreased the elevated levels of TLR4 and tumor necrosis factor-α (TNF-α) induced by inflammation in vivo in this model system. In vitro studies, AOG alone only slightly increased the levels of protein expression and messenger RNA of TLR4, phosphorylation of IκBα and production of TNF-α in HT-29 cells. However, AOG significantly decreased the elevation of all the biomarkers induced by LPS when it was combined with LPS. The effect of AOG may be related to membrane internalization and redistribution of TLR4 from cell membrane to cytoplasm. AOG is active against inflammation and carcinogenesis through targeting LPS/TLR4/NF-κB pathway. Both AOG and LPS are agonists of TLR4 for sharing the same ligand but AOG has a much lower intrinsic activity than that of LPS. AOG may be useful for treatment of colitis and prevention of carcinogenesis in the clinics.

Effects of programmed exercise on depressive symptoms in midlife and older women: A meta-analysis of randomized controlled trials.

PubMed

Pérez-López, Faustino R; Martínez-Domínguez, Samuel J; Lajusticia, Héctor; Chedraui, Peter

2017-12-01

To perform a systematic review and meta-analysis to clarify the effect of programmed exercise on depressive symptoms (DSs) in midlife and older women. We carried out a structured search of PubMed-Medline, Web of Science, Scopus, Embase, Cochrane Library and Scielo, from database inception through June 29, 2017, without language restriction. The search included the following terms: "depression", "depressive symptoms", "exercise", "physical activity", "menopause", and "randomized controlled trial" (RCTs) in midlife and older women. The US, UK and Australian Clinical Trials databases were also searched. We assessed randomized controlled trials (RCTs) that compared the effect of exercise for at least 6 weeks versus no intervention on DSs as the outcome (as defined by trial authors). Exercise was classified according to duration as "mid-term exercise intervention" (MTEI; lasting for 12 weeks to 4 months), and "long-term exercise intervention" (LTEI; lasting for 6-12 months). Mean changes (±standard deviations) in DSs, as assessed with different questionnaires, were extracted to calculate Hedges' g and then used as the effect size for meta-analysis. Standardized mean differences (SMDs) of DSs after intervention were pooled using a random-effects model. Eleven publications were included for analysis related to 1943 midlife and older women (age range 44-55 years minimum to 65.5±4.0 maximum), none of whom was using a hormone therapy. Seven MTEIs were associated with a significant reduction in DSs (SMD=-0.44; 95% CI -0.69, -0.18; p=0.0008) compared with controls. The reduction in DSs was also significant in six LTEIs (SMD=- 0.29; 95% CI -0.49; -0.09; p=0.005). Heterogeneity of effects among studies was moderate to high. Less perceived stress and insomnia (after exercise) were also found as secondary outcomes. Exercise of low to moderate intensity reduces depressive symptoms in midlife and older women. Copyright © 2017. Published by Elsevier B.V.

Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3.

PubMed

Qin, Zhen; Wan, Jing-Jing; Sun, Yang; Wu, Tingyu; Wang, Peng-Yuan; Du, Peng; Su, Ding-Feng; Yang, Yili; Liu, Xia

2017-02-01

Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis, the underlying mechanisms remain not well understood. Our previous finding that nicotine inhibits inflammatory responses through inducing miR-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine against UC. Our present study found that miR-124 expression is upregulated in colon tissues from UC patients and DSS colitis mice. Nicotine treatment further augmented miR-124 expression in lymphocytes isolated from human ulcerative colonic mucosa and ulcerative colon tissues from DSS mice, both in infiltrated lymphocytes and epithelial cells. Moreover, knockdown of miR-124 significantly diminished the beneficial effect of nicotine on murine colitis and IL-6-treated Caco-2 colon epithelial cells. Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6 treated Caco-2 cells and Jurkat human T lymphocytes, in which miR-124 knockdown led to increased activation of STAT3. Blocking STAT3 activity alone is beneficial for DSS colitis and also abolished nicotine's protective effect in this model. These data indicate that nicotine exerts its protective action in UC through inducing miR-124 and inhibiting STAT3, and suggest that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC. Nicotine upregulates miR-124 expression in ulcerative colon tissues and cells. MiR-124 is required for the protective role of nicotine in DSS colitis mice and epithelial cells. The protective effect of nicotine in murine DSS colitis depends on blocking STAT3 activation. MiR-124 mediates the inhibitory role of nicotine on STAT3/p-STAT3. Targeting miR-124 and STAT3 represents a novel approach for treating ulcerative colitis.

Tomato Lycopene Extract Prevents Lipopolysaccharide-Induced NF-κB Signaling but Worsens Dextran Sulfate Sodium-Induced Colitis in NF-κBEGFP Mice

PubMed Central

Joo, Young-Eun; Karrasch, Thomas; Mühlbauer, Marcus; Allard, Brigitte; Narula, Acharan; Herfarth, Hans H.; Jobin, Christian

2009-01-01

Background The impact of tomato lycopene extract (TLE) on intestinal inflammation is currently unknown. We investigated the effect of TLE on lipopolysaccharide (LPS)-induced innate signaling and experimental colitis. Methodology/Principal Findings Mice were fed a diet containing 0.5 and 2% TLE or isoflavone free control (AIN-76). The therapeutic efficacy of TLE diet was assessed using dextran sulfate sodium (DSS) exposed mice and IL-10−/−;NF-κBEGFP mice, representing an acute and spontaneous chronic colitis model respectively. A mini-endoscope was used to determine the extent of macroscopic mucosal lesions. Murine splenocytes and intestinal epithelial cells were used to determine the in vitro impact of TLE on LPS-induced NF-κB signaling. In vitro, TLE blocked LPS-induced IκBα degradation, RelA translocation, NF-κB transcriptional activity and MIP-2 mRNA accumulation in IEC-18 cells. Moreover, LPS-induced IL-12p40 gene expression was dose-dependently inhibited in TLE-treated splenocytes. Interestingly, DSS-induced acute colitis worsened in TLE-fed NF-κBEGFP mice compared to control diet as measured by weight loss, colonoscopic analysis and histological scores. In contrast, TLE-fed IL-10−/−;NF-κBEGFP mice displayed decreased colonic EGFP expression compared to control diet. IL-6, TNFα, and MCP-1 mRNA expression were increased in the colon of TLE-fed, DSS-exposed NF-κBEGFP mice compared to the control diet. Additionally, caspase-3 activation and TUNEL positive cells were enhanced in TLE diet-fed, DSS-exposed mice as compared to DSS control mice. Conclusions/ Significance These results indicate that TLE prevents LPS-induced proinflammatory gene expression by blocking of NF-κB signaling, but aggravates DSS-induced colitis by enhancing epithelial cell apoptosis. PMID:19234608

Benchmarking Collaborative Inter and Intra-agency Enhancements to a Decision Support System for Global Crop Production Assessments

NASA Astrophysics Data System (ADS)

Hutchinson, C. F.; van Leeuwen, W.; Doorn, B.; Drake, S.; Haithcoat, T.; Kaupp, V.; Likholetov, V.; Sheffner, E.; Tralli, D.

2008-12-01

The Office of Global Analysis/ International Production Assessment Branch (IGA/IPA; formerly the Production Estimates and Crop Assessment Division (PECAD)), of the United States Department of Agriculture - Foreign Agricultural Service (USDA-FAS) has been assimilates data and information products from the National Aeronautics and Space Administration (NASA) into its operational decision support system (DSS). The intent is to improve monthly estimates of global production of selected agricultural commodities that are provided to the World Agricultural Outlook Board (WAOB). This research builds on the intermittent collaboration between USDA and NASA in remote sensing of agriculture since 1974. The goal of the research was to develop an approach to measure changes in system performance after the assimilation of NASA products. An important first step was to develop a baseline characterization of the DSS, the working environment and its constraints including the identification of issues and potential solutions. Both qualitative and quantitative information were gathered to benchmark IGA/IPA's DSS using data from questionnaires and interviews. An interactive risk management tool developed for NASA mission architecture design (DDP - Defect Detection and Prevention) was used to evaluate the effectiveness of various Mitigation options against potential Risks, with quantified attainment of Objectives being the most important benchmarking indicator to examine the effectiveness of the assimilation of NASA products into IGA/IPA's DSS. The collaborative benchmarking activities provided not only feedback about the benefits of DSS enhancement to USDA/FAS and NASA, but facilitated communication among DSS users, developers, and USDA management that helped to suggest future avenues for system development as well as improved intra- and interagency collaboration. From this research emerged a model for benchmarking DSSs that (1) promotes continuity and synergy within and between agencies, (2) accommodates scientific, operational and architectural dynamics, and (3) facilitates transfer of knowledge among researchers, management, and decision makers, as well as among decision making agencies.

DSS range delay calibrations: Current performance level

NASA Technical Reports Server (NTRS)

Spradlin, G. L.

1976-01-01

A means for evaluating Deep Space Station (DSS) range delay calibration performance was developed. Inconsistencies frequently noted in these data are resolved. Development of the DSS range delay data base is described. The data base is presented with comments regarding apparent discontinuities. Data regarding the exciter frequency dependence of the delay values are presented. The improvement observed in the consistency of current DSS range delay calibration data over the performance previously observed is noted.

DSS-24 microwave holography measurements

NASA Technical Reports Server (NTRS)

Rochblatt, D. J.; Withington, P. M.; Jackson, H. J.

1995-01-01

The JPL DSN Microwave Antenna Holography System (MAHST) was applied to the newly constructed DSS-24 34-m beam-waveguide antenna at Goldstone, California. The application of MAHST measurements and corrections at DSS 24 provided the critical RF performance necessary to not only meet the project requirements and goals, but to surpass them. A performance increase of 0.35 dB at X-band (8.45 GHz) and 4.9 dB at Ka-band (32 GHz) was provided by MAHST, resulting in peak efficiencies of 75.25 percent at X-band and 60.6 percent at Ka-band (measured from the Cassegrain focus at f1). The MAHST enabled setting the main reflector panels of DSS 24 to 0.25-mm rms, making DSS 24 the highest precision antenna in the NASA/JPL DSN. The precision of the DSS-24 antenna (diameter/rms) is 1.36 x 10(exp 5), and its gain limit is at 95 GHz.

Influence of extra virgin olive oil diet enriched with hydroxytyrosol in a chronic DSS colitis model.

PubMed

Sánchez-Fidalgo, Susana; Sánchez de Ibargüen, L; Cárdeno, A; Alarcón de la Lastra, C

2012-06-01

Recent epidemiological studies have shown that habitual consumption of extra virgin olive oil (EVOO), the characteristic culinary fat of the Mediterranean area, is effective in the prevention of diverse types of digestive disorders such as inflammatory bowel disease. Many of these benefits are, in addition to its high proportion of oleic acid, due to the high content of phenolic compounds. Six-week-old mice were randomized into three dietary groups: standard, EVOO and hydroxytyrosol-enriched EVOO. After 30 days, mice that were exposed to 3% DSS for 5 days developed acute colitis that progressed to severe chronic inflammation during a regime of 21 days of water. Diets enriched with EVOO significantly attenuated the clinical and histological signs of damage, improving results from disease activity index and reducing about 50% the mortality caused by DSS. Moreover, hydroxytyrosol supplement showed better results. Cytokines study showed that TNF-α was maintained near to sham control and IL-10 levels were significantly improved in EVOO and EVOO plus hydroxytyrosol diet-DSS groups. In the same way, COX-2 and iNOS were downregulated, and the activation of p38 MAPK was reduced. We also observed a higher significant reduction in iNOS in hydroxytyrosol-enriched EVOO compared with EVOO alone. EVOO diets exerted a noteworthy beneficial effect in chronic DSS-induced colitis by cytokine modulation and COX-2 and iNOS reduction via downregulation of p38 MAPK. In addition to the beneficial effect by EVOO, supplementation of the diet with hydroxytyrosol may improve chronic colitis through iNOS downregulation plus its antioxidant capacity.

A maritime decision support system to assess risk in the presence of environmental uncertainties: the REP10 experiment

NASA Astrophysics Data System (ADS)

Grasso, Raffaele; Cococcioni, Marco; Mourre, Baptiste; Chiggiato, Jacopo; Rixen, Michel

2012-03-01

The aim of this work is to report on an activity carried out during the 2010 Recognized Environmental Picture experiment, held in the Ligurian Sea during summer 2010. The activity was the first at-sea test of the recently developed decision support system (DSS) for operation planning, which had previously been tested in an artificial experiment. The DSS assesses the impact of both environmental conditions (meteorological and oceanographic) and non-environmental conditions (such as traffic density maps) on people and assets involved in the operation and helps in deciding a course of action that allows safer operation. More precisely, the environmental variables (such as wind speed, current speed and significant wave height) taken as input by the DSS are the ones forecasted by a super-ensemble model, which fuses the forecasts provided by multiple forecasting centres. The uncertainties associated with the DSS's inputs (generally due to disagreement between forecasts) are propagated through the DSS's output by using the unscented transform. In this way, the system is not only able to provide a traffic light map ( run/ not run the operation), but also to specify the confidence level associated with each action. This feature was tested on a particular type of operation with underwater gliders: the glider surfacing for data transmission. It is also shown how the availability of a glider path prediction tool provides surfacing options along the predicted path. The applicability to different operations is demonstrated by applying the same system to support diver operations.

Preventive rather than therapeutic treatment with high fiber diet attenuates clinical and inflammatory markers of acute and chronic DSS-induced colitis in mice.

PubMed

Silveira, Ana Letícia Malheiros; Ferreira, Adaliene Versiani Matos; de Oliveira, Marina Chaves; Rachid, Milene Alvarenga; da Cunha Sousa, Larissa Fonseca; Dos Santos Martins, Flaviano; Gomes-Santos, Ana Cristina; Vieira, Angelica Thomaz; Teixeira, Mauro Martins

2017-02-01

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with important impact on global health. Prebiotic and probiotic strategies are thought to be useful in the context of experimental IBD. Here, we compared the effects of preventive versus therapeutic treatment with a high fiber diet (prebiotic) in combination or not with Bifidobacterium longum (probiotic) in a murine model of chronic colitis. Colitis was induced by adding dextran sulfate sodium (DSS) to drinking water for 6 days (acute colitis) or for 5 cycles of DSS (chronic colitis). Administration of the high fiber diet protected from acute colitis. Protection was optimal when diet was started 20 days prior to DSS. A 5-day pretreatment with acetate, a short-chain fatty acid, provided partial protection against acute colitis. In chronic colitis, pretreatment with the high fiber diet attenuated clinical and inflammatory parameters of disease. However, when the treatment with the high fiber diet started after disease had been established, overall protection was minimal. Similarly, delayed treatment with acetate or B. longum did not provide any protection even when the probiotic was associated with the high fiber diet. Preventive use of a high fiber diet or acetate clearly protects mice against acute and chronic damage induced by DSS in mice. However, protection is lost when therapies are initiated after disease has been established. These results suggest that any therapy aimed at modifying the gut environment (e.g., prebiotic or probiotic strategies) should be given early in the course of disease.

Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice

PubMed Central

Wang, Lihong; Shi, Yan; Cao, Hanwei; Liu, Liping; Washington, M. Kay; Chaturvedi, Rupesh; Israel, Dawn A.; Cao, Hailong; Wang, Bangmao; Peek, Richard M.; Wilson, Keith T.; Polk, D. Brent

2012-01-01

Inflammatory bowel disease (IBD) results from dysregulation of intestinal mucosal immune responses to microflora in genetically susceptible hosts. A major challenge for IBD research is to develop new strategies for treating this disease. Berberine, an alkaloid derived from plants, is an alternative medicine for treating bacterial diarrhea and intestinal parasite infections. Recent studies suggest that berberine exerts several other beneficial effects, including inducing anti-inflammatory responses. This study determined the effect of berberine on treating dextran sulfate sodium (DSS)-induced intestinal injury and colitis in mice. Berberine was administered through gavage to mice with established DSS-induced intestinal injury and colitis. Clinical parameters, intestinal integrity, proinflammatory cytokine production, and signaling pathways in colonic macrophages and epithelial cells were determined. Berberine ameliorated DSS-induced body weight loss, myeloperoxidase activity, shortening of the colon, injury, and inflammation scores. DSS-upregulated proinflammatory cytokine levels in the colon, including TNF, IFN-γ, KC, and IL-17 were reduced by berberine. Berberine decreased DSS-induced disruption of barrier function and apoptosis in the colon epithelium. Furthermore, berberine inhibited proinflammatory cytokine production in colonic macrophages and epithelial cells in DSS-treated mice and promoted apoptosis of colonic macrophages. Activation of signaling pathways involved in stimulation of proinflammatory cytokine production, including MAPK and NF-κB, in colonic macrophages and epithelial cells from DSS-treated mice was decreased by berberine. In summary, berberine promotes recovery of DSS-induced colitis and exerts inhibitory effects on proinflammatory responses in colonic macrophages and epithelial cells. Thus berberine may represent a new therapeutic approach for treating gastrointestinal inflammatory disorders. PMID:22173918

The Crustal Structure of the North-South Earthquake Belt in China Revealed from Deep Seismic Soundings and Gravity Data

NASA Astrophysics Data System (ADS)

Zhao, Yang; Guo, Lianghui; Shi, Lei; Li, Yonghua

2018-01-01

The North-South earthquake belt (NSEB) is one of the major earthquake regions in China. The studies of crustal structure play a great role in understanding tectonic evolution and in evaluating earthquake hazards in this region. However, some fundamental crustal parameters, especially crustal interface structure, are not clear in this region. In this paper, we reconstructed the crustal interface structure around the NSEB based on both the deep seismic sounding (DSS) data and the gravity data. We firstly reconstructed the crustal structure of crystalline basement (interface G), interface between upper and lower crusts (interface C) and Moho in the study area by compiling the results of 38 DSS profiles published previously. Then, we forwardly calculated the gravity anomalies caused by the interfaces G and C, and then subtracted them from the complete Bouguer gravity anomalies, yielding the regional gravity anomalies mainly due to the Moho interface. We then utilized a lateral-variable density interface inversion technique with constraints of the DSS data to invert the regional anomalies for the Moho depth model in the study area. The reliability of our Moho depth model was evaluated by comparing with other Moho depth models derived from other gravity inversion technique and receiver function analysis. Based on our Moho depth model, we mapped the crustal apparent density distribution in the study area for better understanding the geodynamics around the NSEB.

An Internet Protocol-Based Software System for Real-Time, Closed-Loop, Multi-Spacecraft Mission Simulation Applications

NASA Technical Reports Server (NTRS)

Davis, George; Cary, Everett; Higinbotham, John; Burns, Richard; Hogie, Keith; Hallahan, Francis

2003-01-01

The paper will provide an overview of the web-based distributed simulation software system developed for end-to-end, multi-spacecraft mission design, analysis, and test at the NASA Goddard Space Flight Center (GSFC). This software system was developed for an internal research and development (IR&D) activity at GSFC called the Distributed Space Systems (DSS) Distributed Synthesis Environment (DSE). The long-term goal of the DSS-DSE is to integrate existing GSFC stand-alone test beds, models, and simulation systems to create a "hands on", end-to-end simulation environment for mission design, trade studies and simulations. The short-term goal of the DSE was therefore to develop the system architecture, and then to prototype the core software simulation capability based on a distributed computing approach, with demonstrations of some key capabilities by the end of Fiscal Year 2002 (FY02). To achieve the DSS-DSE IR&D objective, the team adopted a reference model and mission upon which FY02 capabilities were developed. The software was prototyped according to the reference model, and demonstrations were conducted for the reference mission to validate interfaces, concepts, etc. The reference model, illustrated in Fig. 1, included both space and ground elements, with functional capabilities such as spacecraft dynamics and control, science data collection, space-to-space and space-to-ground communications, mission operations, science operations, and data processing, archival and distribution addressed.

A Distributed Simulation Software System for Multi-Spacecraft Missions

NASA Technical Reports Server (NTRS)

Burns, Richard; Davis, George; Cary, Everett

2003-01-01

The paper will provide an overview of the web-based distributed simulation software system developed for end-to-end, multi-spacecraft mission design, analysis, and test at the NASA Goddard Space Flight Center (GSFC). This software system was developed for an internal research and development (IR&D) activity at GSFC called the Distributed Space Systems (DSS) Distributed Synthesis Environment (DSE). The long-term goal of the DSS-DSE is to integrate existing GSFC stand-alone test beds, models, and simulation systems to create a "hands on", end-to-end simulation environment for mission design, trade studies and simulations. The short-term goal of the DSE was therefore to develop the system architecture, and then to prototype the core software simulation capability based on a distributed computing approach, with demonstrations of some key capabilities by the end of Fiscal Year 2002 (FY02). To achieve the DSS-DSE IR&D objective, the team adopted a reference model and mission upon which FY02 capabilities were developed. The software was prototyped according to the reference model, and demonstrations were conducted for the reference mission to validate interfaces, concepts, etc. The reference model, illustrated in Fig. 1, included both space and ground elements, with functional capabilities such as spacecraft dynamics and control, science data collection, space-to-space and space-to-ground communications, mission operations, science operations, and data processing, archival and distribution addressed.

Modeling Water Resource Systems Accounting for Water-Related Energy Use, GHG Emissions and Water-Dependent Energy Generation in California

NASA Astrophysics Data System (ADS)

Escriva-Bou, A.; Lund, J. R.; Pulido-Velazquez, M.; Medellin-Azuara, J.

2015-12-01

Most individual processes relating water and energy interdependence have been assessed in many different ways over the last decade. It is time to step up and include the results of these studies in management by proportionating a tool for integrating these processes in decision-making to effectively understand the tradeoffs between water and energy from management options and scenarios. A simple but powerful decision support system (DSS) for water management is described that includes water-related energy use and GHG emissions not solely from the water operations, but also from final water end uses, including demands from cities, agriculture, environment and the energy sector. Because one of the main drivers of energy use and GHG emissions is water pumping from aquifers, the DSS combines a surface water management model with a simple groundwater model, accounting for their interrelationships. The model also explicitly includes economic data to optimize water use across sectors during shortages and calculate return flows from different uses. Capabilities of the DSS are demonstrated on a case study over California's intertied water system. Results show that urban end uses account for most GHG emissions of the entire water cycle, but large water conveyance produces significant peaks over the summer season. Also the development of more efficient water application on the agricultural sector has increased the total energy consumption and the net water use in the basins.

A decision support system (GesCoN) for managing fertigation in open field vegetable crops. Part I-methodological approach and description of the software.

PubMed

Elia, Antonio; Conversa, Giulia

2015-01-01

Reduced water availability and environmental pollution caused by nitrogen (N) losses have increased the need for rational management of irrigation and N fertilization in horticultural systems. Decision support systems (DSS) could be powerful tools to assist farmers to improve irrigation and N fertilization efficiency. Currently, fertilization by drip irrigation system (fertigation) is used for many vegetable crops around the world. The paper illustrates the theoretical basis, the methodological approach and the structure of a DSS called GesCoN for fertigation management in open field vegetable crops. The DSS is based on daily water and N balance, considering the water lost by evapotranspiration (ET) and the N content in the aerial part of the crop (N uptake) as subtraction and the availability of water and N in the wet soil volume most effected by roots as the positive part. For the water balance, reference ET can be estimated using the Penman-Monteith (PM) or the Priestley-Taylor and Hargreaves models, specifically calibrated under local conditions. Both single or dual Kc approach can be used to calculate crop ET. Rain runoff and deep percolation are considered to calculate the effective rainfall. The soil volume most affected by the roots, the wet soil under emitters and their interactions are modeled. Crop growth is modeled by a non-linear logistic function on the basis of thermal time, but the model takes into account thermal and water stresses and allows an in-season calibration through a dynamic adaptation of the growth rate to the specific genetic and environmental conditions. N crop demand is related to DM accumulation by the N critical curve. N mineralization from soil organic matter is daily estimated. The DSS helps users to evaluate the daily amount of water and N fertilizer that has to be applied in order to fulfill the water and N-crop requirements to achieve the maximum potential yield, while reducing the risk of nitrate outflows.

Stress corrosion cracking of duplex stainless steels in caustic solutions

NASA Astrophysics Data System (ADS)

Bhattacharya, Ananya

Duplex stainless steels (DSS) with roughly equal amount of austenite and ferrite phases are being used in industries such as petrochemical, nuclear, pulp and paper mills, de-salination plants, marine environments, and others. However, many DSS grades have been reported to undergo corrosion and stress corrosion cracking in some aggressive environments such as chlorides and sulfide-containing caustic solutions. Although stress corrosion cracking of duplex stainless steels in chloride solution has been investigated and well documented in the literature but the SCC mechanisms for DSS in caustic solutions were not known. Microstructural changes during fabrication processes affect the overall SCC susceptibility of these steels in caustic solutions. Other environmental factors, like pH of the solution, temperature, and resulting electrochemical potential also influence the SCC susceptibility of duplex stainless steels. In this study, the role of material and environmental parameters on corrosion and stress corrosion cracking of duplex stainless steels in caustic solutions were investigated. Changes in the DSS microstructure by different annealing and aging treatments were characterized in terms of changes in the ratio of austenite and ferrite phases, phase morphology and intermetallic precipitation using optical micrography, SEM, EDS, XRD, nano-indentation and microhardness methods. These samples were then tested for general and localized corrosion susceptibility and SCC to understand the underlying mechanisms of crack initiation and propagation in DSS in the above-mentioned environments. Results showed that the austenite phase in the DSS is more susceptible to crack initiation and propagation in caustic solutions, which is different from that in the low pH chloride environment where the ferrite phase is the more susceptible phase. This study also showed that microstructural changes in duplex stainless steels due to different heat treatments could affect their SCC susceptibility. Annealed and water quenched specimens were found to be immune to SCC in caustic environment. Aging treatment at 800°C gave rise to sigma and chi precipitates in the DSS. However, these sigma and chi precipitates, known to initiate cracking in DSS in chloride environment did not cause any cracking of DSS in caustic solutions. Aging of DSS at 475°C had resulted in '475°C embrittlement' and caused cracks to initiate in the ferrite phase. This was in contrast to the cracks initiating in the austenite phase in the as-received DSS. Alloy composition and microstructure of DSS as well as solution composition (dissolved ionic species) was also found to affect the electrochemical behavior and passivation of DSS which in turn plays a major role in stress corrosion crack initiation and propagation. Corrosion rates and SCC susceptibility of DSS was found to increase with addition of sulfide to caustic solutions. Corrosion films on DSS, characterized using XRD and X-ray photoelectron spectroscopy, indicated that the metal sulfide compounds were formed along with oxides at the metal surface in the presence of sulfide containing caustic environments. These metal sulfide containing passive films are unstable and hence breaks down under mechanical straining, leading to SCC initiations. The overall results from this study helped in understanding the mechanism of SCC in caustic solutions. Favorable slip systems in the austenite phase of DSS favors slip-induced local film damage thereby initiating a stress corrosion crack. Repeated film repassivation and breaking, followed by crack tip dissolution results in crack propagation in the austenite phase of DSS alloys. Result from this study will have a significant impact in terms of identifying the alloy compositions, fabrication processes, microstructures, and environmental conditions that may be avoided to mitigate corrosion and stress corrosion cracking of DSS in caustic solutions.

HRMS sky survey wideband feed system design for DSS 24 beam waveguide antenna

NASA Technical Reports Server (NTRS)

Stanton, P. H.; Lee, P. R.; Reilly, H. F.

1993-01-01

The High-Resolution Microwave Survey (HRMS) Sky Survey project will be implemented on the DSS 24 beam waveguide (BWG) antenna over the frequency range of 2.86 to 10 GHz. Two wideband, ring-loaded, corrugated feed horns were designed to cover this range. The horns match the frequency-dependent gain requirements for the DSS 24 BWG system. The performance of the feed horns and the calculated system performance of DSS 24 are presented.

Dietary supplementation and doping-related factors in high-level sailing

PubMed Central

2012-01-01

Background Although dietary supplements (DSs) in sports are considered a natural need resulting from athletes’ increased physical demands, and although they are often consumed by athletes, data on DS usage in Olympic sailing are scarce. The aim of this study was to study the use of and attitudes towards DSs and doping problems in high-level competitive sailing. Methods The sample consisted of 44 high-level sailing athletes (5 of whom were female; total mean age 24.13 ± 6.67 years) and 34 coaches (1 of whom was female; total mean age 37.01 ± 11.70). An extensive, self-administered questionnaire of substance use was used, and the subjects were asked about sociodemographic data, sport-related factors, DS-related factors (i.e., usage of and knowledge about DSs, sources of information), and doping-related factors. The Kruskal-Wallis ANOVA was used to determine the differences in group characteristics, and Spearman’s rank order correlation and a logistic regression analysis were used to define the relationships between the studied variables. Results DS usage is relatively high. More than 77% of athletes consume DSs, and 38% do so on a regular basis (daily). The athletes place a high degree of trust in their coaches and/or physicians regarding DSs and doping. The most important reason for not consuming DSs is the opinion that DSs are useless and a lack of knowledge about DSs. The likelihood of doping is low, and one-third of the subjects believe that doping occurs in sailing (no significant differences between athletes and coaches). The logistic regression found crew number (i.e., single vs. double crew) to be the single significant predictor of DS usage, with a higher probability of DS consumption among single crews. Conclusion Because of the high consumption of DSs future investigations should focus on real nutritional needs in sailing sport. Also, since athletes reported that their coaches are the primary source of information about nutrition and DSs, further studies are necessary to determine the knowledge about nutrition, DSs and doping problems among athletes and their support teams (i.e., coaches, physicians, and strength and conditioning specialists). PMID:23217197

Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector.

PubMed

Sasaki, Makoto; Mathis, J Michael; Jennings, Merilyn H; Jordan, Paul; Wang, Yuping; Ando, Tomoaki; Joh, Takashi; Alexander, J Steven

2005-10-31

Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate), a common model of colitis. Adenoviral IL-10 (Ad-IL10) transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml) within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS), Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10) gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.

Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector

PubMed Central

Sasaki, Makoto; Mathis, J Michael; Jennings, Merilyn H; Jordan, Paul; Wang, Yuping; Ando, Tomoaki; Joh, Takashi; Alexander, J Steven

2005-01-01

Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate), a common model of colitis. Adenoviral IL-10 (Ad-IL10) transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml) within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS), Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10) gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation. PMID:16259632

Statistics of Atmospheric Circulations from Cumulant Expansions

NASA Astrophysics Data System (ADS)

Marston, B.; Sabou, F.

2010-12-01

Large-scale atmospheric flows are not so nonlinear as to preclude their direct statistical simulation (DSS) by systematic expansions in equal-time cumulants. Such DSS offers a number of advantages: (i) Low-order statistics are smoother in space and stiffer in time than the underlying instantaneous flows, hence statistically stationary or slowly varying fixed points can be described with fewer degrees of freedom and can also be accessed rapidly. (ii) Convergence with increasing resolution can be demonstrated. (iii) Finally and most importantly, DSS leads more directly to understanding, by integrating out fast modes, leaving only the slow modes that contain the most interesting information. This makes the approach ideal for simulating and understanding modes of the climate system, including changes in these modes that are driven by climate change. The equations of motion for the cumulants form an infinite hierarchy. The simplest closure is to set the third and higher order cumulants to zero. We extend previous work (Marston, Conover, and Schneider 2008) along these lines to two-layer models of the general circulation which has previously been argued to be only weakly nonlinear (O'Gorman and Schneider, 2006). Equal-time statistics so obtained agree reasonably well with those accumulated by direct numerical simulation (DNS) reproducing efficiently the midlatitude westerlies and storm tracks, tropical easterlies, and non-local teleconnection patterns (Marston 2010). Low-frequency modes of variability can also be captured. The primitive equation model of Held & Suarez, with and without latent heat release, is investigated, providing a test of whether DSS accurately reproduces the responses to simple climate forcings as found by DNS.

Multi-criteria decision analysis using hydrological indicators for decision support - a conceptual framework.

NASA Astrophysics Data System (ADS)

Butchart-Kuhlmann, Daniel; Kralisch, Sven; Meinhardt, Markus; Fleischer, Melanie

2017-04-01

Assessing the quantity and quality of water available in water stressed environments under various potential climate and land-use changes is necessary for good water and environmental resources management and governance. Within the region covered by the Southern African Science Service Centre for Climate Change and Adaptive Land Management (SASSCAL) project, such areas are common. One goal of the SASSCAL project is to develop and provide an integrated decision support system (DSS) with which decision makers (DMs) within a given catchment can obtain objective information regarding potential changes in water flow quantity and timing. The SASSCAL DSS builds upon existing data storage and distribution capability, through the SASSCAL Information System (IS), as well as the J2000 hydrological model. Using output from validated J2000 models, the SASSCAL DSS incorporates the calculation of a range of hydrological indicators based upon Indicators of Hydrological Alteration/Environmental Flow Components (IHA/EFC) calculated for a historic time series (pre-impact) and a set of model simulations based upon a selection of possible climate and land-use change scenarios (post-impact). These indicators, obtained using the IHA software package, are then used as input for a multi-criteria decision analysis (MCDA) undertaken using the open source diviz software package. The results of these analyses will provide DMs with an indication as to how various hydrological indicators within a catchment may be altered under different future scenarios, as well providing a ranking of how each scenario is preferred according to different DM preferences. Scenarios are represented through a combination of model input data and parameter settings in J2000, and preferences are represented through criteria weighting in the MCDA. Here, the methodology is presented and applied to the J2000 Luanginga model results using a set of hypothetical decision maker preference values as input for an MCDA based on the PROMETHEE II outranking method. Future work on the SASSCAL DSS will entail automation of this process, as well as its application to other hydrological models and land-use and/or climate change scenarios.

Using automatically extracted information from mammography reports for decision-support

PubMed Central

Bozkurt, Selen; Gimenez, Francisco; Burnside, Elizabeth S.; Gulkesen, Kemal H.; Rubin, Daniel L.

2016-01-01

Objective To evaluate a system we developed that connects natural language processing (NLP) for information extraction from narrative text mammography reports with a Bayesian network for decision-support about breast cancer diagnosis. The ultimate goal of this system is to provide decision support as part of the workflow of producing the radiology report. Materials and methods We built a system that uses an NLP information extraction system (which extract BI-RADS descriptors and clinical information from mammography reports) to provide the necessary inputs to a Bayesian network (BN) decision support system (DSS) that estimates lesion malignancy from BI-RADS descriptors. We used this integrated system to predict diagnosis of breast cancer from radiology text reports and evaluated it with a reference standard of 300 mammography reports. We collected two different outputs from the DSS: (1) the probability of malignancy and (2) the BI-RADS final assessment category. Since NLP may produce imperfect inputs to the DSS, we compared the difference between using perfect (“reference standard”) structured inputs to the DSS (“RS-DSS”) vs NLP-derived inputs (“NLP-DSS”) on the output of the DSS using the concordance correlation coefficient. We measured the classification accuracy of the BI-RADS final assessment category when using NLP-DSS, compared with the ground truth category established by the radiologist. Results The NLP-DSS and RS-DSS had closely matched probabilities, with a mean paired difference of 0.004 ± 0.025. The concordance correlation of these paired measures was 0.95. The accuracy of the NLP-DSS to predict the correct BI-RADS final assessment category was 97.58%. Conclusion The accuracy of the information extracted from mammography reports using the NLP system was sufficient to provide accurate DSS results. We believe our system could ultimately reduce the variation in practice in mammography related to assessment of malignant lesions and improve management decisions. PMID:27388877

Desktop Application Program to Simulate Cargo-Air-Drop Tests

NASA Technical Reports Server (NTRS)

Cuthbert, Peter

2009-01-01

The DSS Application is a computer program comprising a Windows version of the UNIX-based Decelerator System Simulation (DSS) coupled with an Excel front end. The DSS is an executable code that simulates the dynamics of airdropped cargo from first motion in an aircraft through landing. The bare DSS is difficult to use; the front end makes it easy to use. All inputs to the DSS, control of execution of the DSS, and postprocessing and plotting of outputs are handled in the front end. The front end is graphics-intensive. The Excel software provides the graphical elements without need for additional programming. Categories of input parameters are divided into separate tabbed windows. Pop-up comments describe each parameter. An error-checking software component evaluates combinations of parameters and alerts the user if an error results. Case files can be created from inputs, making it possible to build cases from previous ones. Simulation output is plotted in 16 charts displayed on a separate worksheet, enabling plotting of multiple DSS cases with flight-test data. Variables assigned to each plot can be changed. Selected input parameters can be edited from the plot sheet for quick sensitivity studies.

Gut microbiota drives the attenuation of dextran sulphate sodium-induced colitis by Huangqin decoction

PubMed Central

Ye, Juan; Cai, Xueting; Tsering, Pamo; Cheng, Xiaolan; Hu, Chunping; Zhang, Shuangquan; Cao, Peng

2017-01-01

The gut microbiota, including probiotics and pathogenic microorganisms, is involved in ulcerative colitis (UC) by regulating pathogenic microorganisms and the production of intestinal mucosal antibodies. Huangqin decoction (HQD), a traditional Chinese formula chronicled in the Shanghan lun, has been recognized as an effective drug for UC, owing to its anti-inflammatory and anti-oxidative properties. In the present study, we investigated whether HQD ameliorates dextran sulphate sodium (DSS)-induced colitis through alteration of the gut microbiota. We found that HQD significantly inhibited colitis, alleviating the loss of body weight, disease activity index, colon shortening, tissue injury, and inflammatory cytokine changes induced by DSS treatment. Principal component analysis and principal co-ordinate analysis showed an obvious difference among the groups, with increased diversity in the DSS and DSS+HQD groups. Linear discriminant analysis effect size was used to determine differences between the groups. The relative abundance of Lactococcus was higher in the DSS+HQD group than in the DSS group, whereas Desulfovibrio and Helicobacter were decreased. Furthermore, the protective effect of HQD was attenuated only in antibiotic-treated mice. In conclusion, our results suggest that HQD could ameliorate DSS-induced inflammation through alteration of the gut microbiota. PMID:28415628

A review on chemical-induced inflammatory bowel disease models in rodents.

PubMed

Randhawa, Puneet Kaur; Singh, Kavinder; Singh, Nirmal; Jaggi, Amteshwar Singh

2014-08-01

Ulcerative colitis and Crohn's disease are a set of chronic, idiopathic, immunological and relapsing inflammatory disorders of the gastrointestinal tract referred to as inflammatory bowel disorder (IBD). Although the etiological factors involved in the perpetuation of IBD remain uncertain, development of various animal models provides new insights to unveil the onset and the progression of IBD. Various chemical-induced colitis models are widely used on laboratory scale. Furthermore, these models closely mimic morphological, histopathological and symptomatical features of human IBD. Among the chemical-induced colitis models, trinitrobenzene sulfonic acid (TNBS)-induced colitis, oxazolone induced-colitis and dextran sulphate sodium (DSS)-induced colitis models are most widely used. TNBS elicits Th-1 driven immune response, whereas oxazolone predominantly exhibits immune response of Th-2 phenotype. DSS-induced colitis model also induces changes in Th-1/Th-2 cytokine profile. The present review discusses the methodology and rationale of using various chemical-induced colitis models for evaluating the pathogenesis of IBD.

In vivo biocompatibility of a new cyanine dye for ILM peeling.

PubMed

Thaler, S; Haritoglou, C; Schuettauf, F; Choragiewicz, T; May, C A; Gekeler, F; Fischer, M D; Langhals, H; Schatz, A

2015-03-01

To investigate the biocompatibility of the new cyanine dye: 3,3'-Di-(4-sulfobutyl)-1,1,1',1'-tetramethyl-di-1H-benz[e]indocarbocyanine (DSS) as a vital dye for intraocular application in an in vivo rat model and to evaluate the effects of this dye on retinal structure and function. DSS at a concentration of 0.5% was applied via intravitreal injections to adult Brown Norway rats with BSS serving as a control. Retinal toxicity was assessed 7 days later by means of retinal ganglion cell (RGC) counts, light microscopy, optical coherence tomography (OCT), and electroretinography (ERG). No significant decrease in RGC numbers was observed. No structural changes of the central retina were observed either in vivo (OCT) or under light microscopy. ERGs detected a temporary reduction of retinal function 7 days after injection; this was no longer evident 14 days after injection. DSS showed good biocompatibility in a well-established experimental in vivo setting and may be usable for intraocular surgery as an alternative to other cyanine dyes. In contrast to indocyanine green, it additionally offers fluorescence in the visual spectrum. Further studies with other animal models are needed before translation into clinical application.

The Impact of Epidemiological Factors and Treatment Interventions on Survival in Patients With Signet Ring Cell Carcinoma of the Pancreas.

PubMed

Patel, Mausam; Hans, Harliv S; Pan, Kelsey; Khan, Humza; Donath, Elie; Caldera, Humberto

2018-04-18

Primary pancreatic signet ring cell carcinoma (SRCC) is a rare histologic variant of pancreatic carcinoma. A population-based analysis of pancreatic SRCC was performed to determine the predictive effects of epidemiological factors and treatment interventions on overall survival (OS) and disease-specific survival (DSS). The Surveillance, Epidemiology, and End Results registry was searched for pancreatic SRCC cases diagnosed between January 1, 1973 and December 31, 2013. Statistical analysis was performed using the Fisher exact test, χ analysis, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. The mean age among 497 patients was 66.6 years (SD, 11.9). Most patients were white (82.7%) and male (54.5%). The 1-, 2-, and 5-year OS rates were 17%, 9%, and 4%, respectively, while the corresponding 1-, 2-, and 5-year rates for DSS were 18%, 10%, and 5%, respectively. On univariable analysis; age, site, grade, stage, and treatment were predictive of OS and DSS (P<0.05). On multivariable analysis; radiation improved OS and DSS (adjusted hazard ratio [aHR], 0.592 and 0.589, respectively), pancreatectomy improved OS and DSS (aHR, 0.360 and 0.355, respectively), and combination therapy improved OS and DSS (aHR, 0.295 and 0.286, respectively). Age, site, and stage were also independent predictors of OS and DSS. Subgroup analysis demonstrated treatment to be an independent predictor of OS and DSS in localized/regional disease, in distant disease, and in patients diagnosed between 2000 and 2013. Age, site, stage, and treatment independently predict OS and DSS in pancreatic SRCC.

Resistant starch modulates in vivo colonic butyrate uptake and its oxidation in rats with dextran sulfate sodium-induced colitis.

PubMed

Moreau, Noëlle M; Champ, Martine M; Goupry, Stéphane M; Le Bizec, Bruno J; Krempf, Michel; Nguyen, Patrick G; Dumon, Henri J; Martin, Lucile J

2004-03-01

We previously demonstrated improvements of colonic lesions due to dextran sulfate sodium (DSS) in rats after 7 d of supplementation with resistant starch (RS) type 3, a substrate yielding high levels of butyrate (C(4)), a colonic cell fuel source. In the present study, we hypothesized that if inflammation is related to decreased C(4) utilization by the colonic mucosa, RS supplementation should restore C(4) use simultaneously with an increase in the amount of C(4) present in the digestive tract. Hence, we compared, in vivo, the cecocolonic uptake of C(4) and its oxidation into CO(2) and ketone bodies in control and DSS-treated rats fed a fiber-free basal diet (BD) or a RS-supplemented diet. Sprague-Dawley rats (n = 60) were used. DSS treatment was performed to induce acute colitis and then to maintain chronic colitis. After cecal infusion of [1-(13)C]-C(4) (20 micro mol in 1 h), concentrations and (13)C-enrichment of C(4), ketone bodies, and CO(2) were quantified in the abdominal aorta and portal vein. Portal blood flow was recorded. During acute colitis, (13)C(4) uptake and (13)CO(2) production were lower in DSS rats than in controls. During chronic colitis, DSS rats did not differ from controls. After 7 d of chronic colitis, RS-DSS rats exhibited the same C(4) uptake as BD-DSS rats in spite of higher C(4) cecocolonic disposal. After 14 d, C(4) uptake was higher in RS-DSS than in BD-DSS rats. Thus, the increased utilization of C(4) by the mucosa is subsequent to evidence of healing and appears to be a consequence rather than a cause of this RS healing effect.

Dangguishaoyao-San attenuates LPS-induced neuroinflammation via the TLRs/NF-κB signaling pathway.

PubMed

Ding, Rui-Rui; Chen, Wang; Guo, Cong-Ying; Liao, Wei-Tao; Yang, Xia; Liao, Feng-Er; Lin, Jing-Ming; Mei, Han-Fang; Zeng, Yu

2018-05-29

Dangguishaoyao-San (DSS) is composed of six traditional Chinese medicines, including Angelica sinensis, Paeoniae radix, Rhizoma Ligusticum, Poria cocos, Rhizoma Atractylodis Macrocephalae, and Rhizoma Alismatis. DSS has been reported to be effective in alleviating the symptoms of Alzheimer's disease (AD). The aim of this study was to investigate the mechanism of action of DSS in vitro using lipopolysaccharide (LPS)-stimulated BV-2 microglia cells. BV-2 cells were pretreated with 0.58-1.16 mg/mL of DSS for 2 h and then treated with 1 μg/mL LPS for 24 h. Cell viability was determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The protein expression levels were measured by Western blots. Inflammatory factors were detected by enzyme-linked immunosorbent assays (ELISAs). The mRNA levels of inflammatory factors were analyzed by quantitative real-time PCR (qRT-PCR). DSS treatment at concentrations of 0.58-1.16 mg/mL resulted in no significant cytotoxicity. DSS attenuated the release of pro-inflammatory factors, such as interleukin-1β (IL-1β), iNOS and tumor necrosis factor-α (TNF-α) in LPS-induced BV-2 cells. DSS attenuated the mRNA expression of pro-inflammatory cytokines, TLR2, and TLR4 and decreased TLR4 and TLR protein levels as well as the phosphorylation of IκB in LPS-induced BV-2 cells. DSS also down-regulated the nuclear translocation of p65. This study demonstrated that DSS has a protective effect on neuroinflammation in LPS-induced BV-2 microglia cells through the TLRs/NF-κB signaling pathway. Copyright © 2018. Published by Elsevier Masson SAS.

Jianpi Qingchang decoction alleviates ulcerative colitis by inhibiting nuclear factor-κB activation

PubMed Central

Zheng, Lie; Zhang, Ya-Li; Dai, Yan-Cheng; Chen, Xuan; Chen, De-Liang; Dai, Yue-Ting; Tang, Zhi-Peng

2017-01-01

AIM To investigate the therapeutic effect of Jianpi Qingchang decoction (JPQCD) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. METHODS C57BL/c mice were injected intragastrically with 5% DSS instead of drinking water for 7 d, and their body weight, diarrhea severity and fecal bleeding were monitored, while the mice in the control group were treated with standard drinking water, without DSS. After 7 d, the DSS drinking water was changed to normal water and the DSS group continued with DSS water. The control and DSS groups were given normal saline by intragastric injection. The 5-aminosalicylic acid (5-ASA) group was treated orally with 5-ASA at a dose of 100 mg/kg daily. The JPQCD group was treated orally with JPQCD at a dose of 17.1 g/kg daily. On day 14, the colon length was measured, the colorectal histopathological damage score was assessed, and protein levels of interleukin (IL)-1β, IL-8 and tumor necrosis factor-alpha (TNF-α) in colon supernatants were measured by enzyme-linked immunosorbent assay. mRNA expression of IL-1β, IL-8, TNF-α and nuclear factor-kappa B (NF-κB) was detected by real-time quantitative polymerase chain reaction. Western blotting was used to detect the protein expression of NF-κB and inhibitor of kappa B. RESULTS Acute inflammation occurred in the mice administered DSS, including the symptoms of losing body weight, loose feces/watery diarrhea and presence of fecal blood; all these symptoms worsened at 7 d. The colons of mice treated with DSS were assessed by histological examination, and the results confirmed that acute inflammation had occurred, as evidenced by loss of colonic mucosa and chronic inflammatory cell infiltration, and these features extended into the deeper layer of the colon walls. The expression levels of IL-1β, IL-8 and TNF-α in the DSS group were higher than those in the control group (P < 0.05), and the expression levels of IL-1β, IL-8 and TNF-α in the JPQCD and 5-ASA groups were lower than those in the DSS group after treating with JPQCD and 5-ASA. Comparing with the DSS group, the mRNA level of IL-1β, IL-8, TNF-α and NF-κB was significantly reduced by 5-ASA and JPQCD. The difference between JPQCD and 5-ASA groups was not statistically significant (P > 0.05). Comparing with the DSS group, due to using JPQCD and 5-ASA, significant suppression of activation in DSS-induced NF-κB and increased phosphorylation of IκB in mice with experimental colitis occurred (P < 0.05). The difference between the JPQCD group and the 5-ASA group was not statistically significant (P > 0.05). CONCLUSION Activation of the NF-κB signaling pathway is inhibited by JPQCD, which shows the potential mechanism by which JPQCD treats UC. PMID:28275298

Proceedings of the workshop "Development of biological decision support systems for resource managers": Denver, Colorado, October 27-29, 1998

USGS Publications Warehouse

Getter, James; D'Erchia, Terry D.; Root, Ralph; Getter, James; D'Erchia, Terry D.; Root, Ralph

1999-01-01

The format for this 3-day workshop (27-29 October 1998) included plenary presentations by USGS Biological Resources Division (BRD) and U.S. Fish and Wildlife Service per onnel who u e and develop decision support systems (DSS); breakout ses ions addressing DSS technical information aspect , outreach/ customer requirements, and future perspectives; and a DSS Steering Committee meeting to evaluate work hop goals and to provide guidance for fu ture efforts. Steering committee action item developed from workshop inputs were to ( I) develop a "DSS framework" document for u e in biological research. (2) develop a "proof of concept" DSS based upon the framework document, and (3) integrate decision support ystem into BRD program elements.

CSF-1 Receptor-Dependent Colon Development, Homeostasis and Inflammatory Stress Response

PubMed Central

Huynh, Duy; Akçora, Dilara; Malaterre, Jordane; Chan, Chee Kai; Dai, Xu-Ming; Bertoncello, Ivan; Stanley, E. Richard; Ramsay, Robert G.

2013-01-01

The colony stimulating factor-1 (CSF-1) receptor (CSF-1R) directly regulates the development of Paneth cells (PC) and influences proliferation and cell fate in the small intestine (SI). In the present study, we have examined the role of CSF-1 and the CSF-1R in the large intestine, which lacks PC, in the steady state and in response to acute inflammation induced by dextran sulfate sodium (DSS). As previously shown in mouse, immunohistochemical (IHC) analysis of CSF-1R expression showed that the receptor is baso-laterally expressed on epithelial cells of human colonic crypts, indicating that this expression pattern is shared between species. Colons from Csf1r null and Csf1op/op mice were isolated and sectioned for IHC identification of enterocytes, enteroendocrine cells, goblet cells and proliferating cells. Both Csf1r−/− and Csf1op/op mice were found to have colon defects in enterocytes and enteroendocrine cell fate, with excessive goblet cell staining and reduced cell proliferation. In addition, the gene expression profiles of the cell cycle genes, cyclinD1, c-myc, c-fos, and c-myb were suppressed in Csf1r−/− colonic crypt, compared with those of WT mice and the expression of the stem cell marker gene Lgr5 was markedly reduced. However, analysis of the proliferative responses of immortalized mouse colon epithelial cells (lines; Immorto-5 and YAMC) indicated that CSF-1R is not a major regulator of colonocyte proliferation and that its effects on proliferation are indirect. In an examination of the acute inflammatory response, Csf1r +/− male mice were protected from the adverse affects of DSS-induced colitis compared with WT mice, while Csf1r +/− female mice were significantly less protected. These data indicate that CSF-1R signaling plays an important role in colon homeostasis and stem cell gene expression but that the receptor exacerbates the response to inflammatory challenge in male mice. PMID:23451116

Design and implementation of a beam-waveguide mirror control system for vernier pointing of the DSS-13 antenna

NASA Technical Reports Server (NTRS)

Alvarez, L. S.; Moore, M.; Veruttipong, W.; Andres, E.

1994-01-01

The design and implementation of an antenna beam-waveguide (BWG) mirror position control system at the DSS-13 34-m antenna is presented. While it has several potential applications, a positioner on the last flat-plate BWG mirror (M6) at DSS 13 is installed to demonstrate the conical scan (conscan) angle-tracking technique at the Ka-band (32-GHz) operating frequency. Radio frequency (RF) beam-scanning predictions for the M6 mirror, computed from a diffraction analysis, are presented. From these predictions, position control system requirements are then derived. The final mechanical positioner and servo system designs, as implemented at DSS 13, are illustrated with detailed design descriptions given in the appendices. Preliminary measurements of antenna Ka-band beam scan versus M6 mirror tilt made at DSS 13 in December 1993 are presented. After reduction, the initial measurements are shown to be in agreement with the RF predicts. Plans for preliminary conscan experimentation at DSS 13 are summarized.

Radical lymph node dissection and assessment: Impact on gallbladder cancer prognosis

PubMed Central

Liu, Gui-Jie; Li, Xue-Hua; Chen, Yan-Xin; Sun, Hui-Dong; Zhao, Gui-Mei; Hu, San-Yuan

2013-01-01

AIM: To investigate the lymph node metastasis patterns of gallbladder cancer (GBC) and evaluate the optimal categorization of nodal status as a critical prognostic factor. METHODS: From May 1995 to December 2010, a total of 78 consecutive patients with GBC underwent a radical resection at Liaocheng People’s Hospital. A radical resection was defined as removing both the primary tumor and the regional lymph nodes of the gallbladder. Demographic, operative and pathologic data were recorded. The lymph nodes retrieved were examined histologically for metastases routinely from each node. The positive lymph node count (PLNC) as well as the total lymph node count (TLNC) was recorded for each patient. Then the metastatic to examined lymph nodes ratio (LNR) was calculated. Disease-specific survival (DSS) and predictors of outcome were analyzed. RESULTS: With a median follow-up time of 26.50 mo (range, 2-132 mo), median DSS was 29.00 ± 3.92 mo (5-year survival rate, 20.51%). Nodal disease was found in 37 patients (47.44%). DSS of node-negative patients was significantly better than that of node-positive patients (median DSS, 40 mo vs 17 mo, χ2 = 14.814, P < 0.001), while there was no significant difference between N1 patients and N2 patients (median DSS, 18 mo vs 13 mo, χ2 = 0.741, P = 0.389). Optimal TLNC was determined to be four. When node-negative patients were divided according to TLNC, there was no difference in DSS between TLNC < 4 subgroup and TLNC ≥ 4 subgroup (median DSS, 37 mo vs 54 mo, χ2 = 0.715, P = 0.398). For node-positive patients, DSS of TLNC < 4 subgroup was worse than that of TLNC ≥ 4 subgroup (median DSS, 13 mo vs 21 mo, χ2 = 11.035, P < 0.001). Moreover, for node-positive patients, a new cut-off value of six nodes was identified for the number of TLNC that clearly stratified them into 2 separate survival groups (< 6 or ≥ 6, respectively; median DSS, 15 mo vs 33 mo, χ2 = 11.820, P < 0.001). DSS progressively worsened with increasing PLNC and LNR, but no definite cut-off value could be identified. Multivariate analysis revealed histological grade, tumor node metastasis staging, TNLC and LNR to be independent predictors of DSS. Neither location of positive lymph nodes nor PNLC were identified as an independent variable by multivariate analysis. CONCLUSION: Both TLNC and LNR are strong predictors of outcome after curative resection for GBC. The retrieval and examination of at least 6 nodes can influence staging quality and DSS, especially in node-positive patients. PMID:23964151

Radical lymph node dissection and assessment: Impact on gallbladder cancer prognosis.

PubMed

Liu, Gui-Jie; Li, Xue-Hua; Chen, Yan-Xin; Sun, Hui-Dong; Zhao, Gui-Mei; Hu, San-Yuan

2013-08-21

To investigate the lymph node metastasis patterns of gallbladder cancer (GBC) and evaluate the optimal categorization of nodal status as a critical prognostic factor. From May 1995 to December 2010, a total of 78 consecutive patients with GBC underwent a radical resection at Liaocheng People's Hospital. A radical resection was defined as removing both the primary tumor and the regional lymph nodes of the gallbladder. Demographic, operative and pathologic data were recorded. The lymph nodes retrieved were examined histologically for metastases routinely from each node. The positive lymph node count (PLNC) as well as the total lymph node count (TLNC) was recorded for each patient. Then the metastatic to examined lymph nodes ratio (LNR) was calculated. Disease-specific survival (DSS) and predictors of outcome were analyzed. With a median follow-up time of 26.50 mo (range, 2-132 mo), median DSS was 29.00 ± 3.92 mo (5-year survival rate, 20.51%). Nodal disease was found in 37 patients (47.44%). DSS of node-negative patients was significantly better than that of node-positive patients (median DSS, 40 mo vs 17 mo, χ² = 14.814, P < 0.001), while there was no significant difference between N1 patients and N2 patients (median DSS, 18 mo vs 13 mo, χ² = 0.741, P = 0.389). Optimal TLNC was determined to be four. When node-negative patients were divided according to TLNC, there was no difference in DSS between TLNC < 4 subgroup and TLNC ≥ 4 subgroup (median DSS, 37 mo vs 54 mo, χ² = 0.715, P = 0.398). For node-positive patients, DSS of TLNC < 4 subgroup was worse than that of TLNC ≥ 4 subgroup (median DSS, 13 mo vs 21 mo, χ² = 11.035, P < 0.001). Moreover, for node-positive patients, a new cut-off value of six nodes was identified for the number of TLNC that clearly stratified them into 2 separate survival groups (< 6 or ≥ 6, respectively; median DSS, 15 mo vs 33 mo, χ² = 11.820, P < 0.001). DSS progressively worsened with increasing PLNC and LNR, but no definite cut-off value could be identified. Multivariate analysis revealed histological grade, tumor node metastasis staging, TNLC and LNR to be independent predictors of DSS. Neither location of positive lymph nodes nor PNLC were identified as an independent variable by multivariate analysis. Both TLNC and LNR are strong predictors of outcome after curative resection for GBC. The retrieval and examination of at least 6 nodes can influence staging quality and DSS, especially in node-positive patients.

Linking a modified EPIC-based growth model (UPGM) with a component-based watershed model (AGES-W)

USDA-ARS?s Scientific Manuscript database

Agricultural models and decision support systems (DSS) for assessing water use and management are increasingly being applied to diverse geographic regions at different scales. This requires models that can simulate different crops, however, very few plant growth models are available that “easily” ...

NASA Data for Water Resources Applications

NASA Technical Reports Server (NTRS)

Toll, David; Houser, Paul; Arsenault, Kristi; Entin, Jared

2004-01-01

Water Management Applications is one of twelve elements in the Earth Science Enterprise National Applications Program. NASA Goddard Space Flight Center is supporting the Applications Program through partnering with other organizations to use NASA project results, such as from satellite instruments and Earth system models to enhance the organizations critical needs. The focus thus far has been: 1) estimating water storage including snowpack and soil moisture, 2) modeling and predicting water fluxes such as evapotranspiration (ET), precipitation and river runoff, and 3) remote sensing of water quality, including both point source (e.g., turbidity and productivity) and non-point source (e.g., land cover conversion such as forest to agriculture yielding higher nutrient runoff). The objectives of the partnering cover three steps of: 1) Evaluation, 2) Verification and Validation, and 3) Benchmark Report. We are working with the U.S. federal agencies including the Environmental Protection Agency (EPA), the Bureau of Reclamation (USBR) and the Department of Agriculture (USDA). We are using several of their Decision Support Systems (DSS) tools. This includes the DSS support tools BASINS used by EPA, Riverware and AWARDS ET ToolBox by USBR and SWAT by USDA and EPA. Regional application sites using NASA data across the US. are currently being eliminated for the DSS tools. The current NASA data emphasized thus far are from the Land Data Assimilation Systems WAS) and MODIS satellite products. We are currently in the first two steps of evaluation and verification validation. Water Management Applications is one of twelve elements in the Earth Science Enterprise s National Applications Program. NASA Goddard Space Flight Center is supporting the Applications Program through partnering with other organizations to use NASA project results, such as from satellite instruments and Earth system models to enhance the organizations critical needs. The focus thus far has been: 1) estimating water storage including snowpack and soil moisture, 2) modeling and predicting water fluxes such as evapotranspiration (ET), precipitation and river runoff, and 3) remote sensing of water quality, including both point source (e.g., turbidity and productivity) and non-point source (e.g., land cover conversion such as forest to agriculture yielding higher nutrient runoff). The objectives of the partnering cover three steps of 1) Evaluation, 2) Verification and Validation, and 3) Benchmark Report. We are working with the U.S. federal agencies the Environmental Protection Agency (EPA), the Bureau of Reclamation (USBR) and the Department of Agriculture (USDA). We are using several of their Decision Support Systems (DSS) tools. T us includes the DSS support tools BASINS used by EPA, Riverware and AWARDS ET ToolBox by USBR and SWAT by USDA and EPA. Regional application sites using NASA data across the US. are currently being evaluated for the DSS tools. The current NASA data emphasized thus far are from the Land Data Assimilation Systems (LDAS) and MODIS satellite products. We are currently in the first two steps of evaluation and verification and validation.

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. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Synthetic peptides derived from salivary proteins and the control of surface charge densities of dental surfaces improve the inhibition of dental calculus formation.

PubMed

Grohe, Bernd

2017-08-01

Peptides descended from the salivary proteins statherin and histatin were recently identified in saliva and the acquired enamel pellicle (AEP), a proteomic layer coated on enamel. In particular, the statherin phosphopeptide DpSpSEEKFLR (DSS) was found to adsorb to enamel-like hydroxyapatite and inhibit plaque-related crystal formation. To determine the mechanism of these processes, we studied peptide-crystal interactions based on the sequences DSS and RKFHEKHHSHRGYR (RKF). The latter is a basic histatin sequence showing antimicrobial effects. To initiate crystallization we used calcium oxalate monohydrate (COM), a rather secondary phase in the oral environment, however highly amenable to experimental analyses of nucleation and growth processes. Using electron microscopy we found that the peptides DSS, DSS-RKF and DSS-DSS all inhibit crystal formation; with DSS-DSS showing the strongest effects while RKF showed no effect. In addition, using either enamel-like or mica substrates, we found that the ratio of the substrate's surface charge densities was directly correlated with the ratio of COM nucleation rates on theses surfaces. The findings suggest that mineralization processes on enamel/AEP-films are controllable by the degree of peptide phosphorylation/acidity and the level of the enamel surface charge density. Both parameters can, when well adjusted, help to overcome periodontal disease and dental calculus formation. In addition, the presence of antimicrobial RKF will reduce the buildup of bacterial plaque. Copyright © 2017 Elsevier B.V. All rights reserved.

Intestinal CCL11 and eosinophilic inflammation is regulated by myeloid cell-specific RelA/p65 in mice.

PubMed

Waddell, Amanda; Ahrens, Richard; Tsai, Yi-Ting; Sherrill, Joseph D; Denson, Lee A; Steinbrecher, Kris A; Hogan, Simon P

2013-05-01

In inflammatory bowel diseases (IBDs), particularly ulcerative colitis, intestinal macrophages (MΦs), eosinophils, and the eosinophil-selective chemokine CCL11, have been associated with disease pathogenesis. MΦs, a source of CCL11, have been reported to be of a mixed classical (NF-κB-mediated) and alternatively activated (STAT-6-mediated) phenotype. The importance of NF-κB and STAT-6 pathways to the intestinal MΦ/CCL11 response and eosinophilic inflammation in the histopathology of experimental colitis is not yet understood. Our gene array analyses demonstrated elevated STAT-6- and NF-κB-dependent genes in pediatric ulcerative colitis colonic biopsies. Dextran sodium sulfate (DSS) exposure induced STAT-6 and NF-κB activation in mouse intestinal F4/80(+)CD11b(+)Ly6C(hi) (inflammatory) MΦs. DSS-induced CCL11 expression, eosinophilic inflammation, and histopathology were attenuated in RelA/p65(Δmye) mice, but not in the absence of STAT-6. Deletion of p65 in myeloid cells did not affect inflammatory MΦ recruitment or alter apoptosis, but did attenuate LPS-induced cytokine production (IL-6) and Ccl11 expression in purified F4/80(+)CD11b(+)Ly6C(hi) inflammatory MΦs. Molecular and cellular analyses revealed a link between expression of calprotectin (S100a8/S100a9), Ccl11 expression, and eosinophil numbers in the DSS-treated colon. In vitro studies of bone marrow-derived MΦs showed calprotectin-induced CCL11 production via a p65-dependent mechanism. Our results indicate that myeloid cell-specific NF-κB-dependent pathways play an unexpected role in CCL11 expression and maintenance of eosinophilic inflammation in experimental colitis. These data indicate that targeting myeloid cells and NF-κB-dependent pathways may be of therapeutic benefit for the treatment of eosinophilic inflammation and histopathology in IBD.

Intestinal CCL11 and eosinophilic inflammation is regulated by myeloid cell-specific RelA/p65 in mice

PubMed Central

Waddell, Amanda; Ahrens, Richard; Tsai, Yi Ting; Sherrill, Joseph D.; Denson, Lee A.; Steinbrecher, Kris A.; Hogan, Simon P.

2014-01-01

In inflammatory bowel diseases (IBD), particularly ulcerative colitis (UC), intestinal macrophages (MΦs), eosinophils and the eosinophil-selective chemokine CCL11 have been associated with disease pathogenesis. MΦs, a source of CCL11, have been reported to be of a mixed classical (NF-κB-mediated) and alternatively activated (STAT-6-mediated) phenotype. The importance of NF-κB and STAT-6 pathways to the intestinal MΦ/CCL11 response and eosinophilic inflammation in the histopathology of experimental colitis is not yet understood. Our gene array analyses demonstrated elevated STAT-6- and NF-κB-dependent genes in pediatric UC colonic biopsies. Dextran sodium sulphate (DSS) exposure induced STAT-6 and NF-κB activation in mouse intestinal F4/80+CD11b+Ly6Chi (inflammatory) MΦs. DSS-induced CCL11 expression, eosinophilic inflammation and histopathology were attenuated in RelA/p65Δmye mice but not in the absence of STAT-6. Deletion of p65 in myeloid cells did not affect inflammatory MΦ recruitment or alter apoptosis, but did attenuate lipopolysaccharide-induced cytokine production (IL-6) and Ccl11 expression in purified F4/80+CD11b+Ly6Chi inflammatory MΦs. Molecular and cellular analyses revealed a link between expression of calprotectin (S100a8/S100a9), Ccl11 expression and eosinophil numbers in the DSS-treated colon. In vitro studies of bone marrow-derived MΦs showed calprotectin-induced CCL11 production via a p65-dependent mechanism. Our results indicate that myeloid cell-specific NF-κB-dependent pathways play an unexpected role in CCL11 expression and maintenance of eosinophilic inflammation in experimental colitis. These data indicate that targeting myeloid cells and NF-κB-dependent pathways may be of therapeutic benefit for the treatment of eosinophilic inflammation and histopathology in IBD. PMID:23562811

WAR DSS: A DECISION SUPPORT SYSTEM FOR ENVIRONMENTALLY CONSCIOUS CHEMICAL PROCESS DESIGN

EPA Science Inventory

The second generation of the Waste Reduction (WAR) Algorithm is constructed as a decision support system (DSS) in the design of chemical manufacturing facilities. The WAR DSS is a software tool that can help reduce the potential environmental impacts (PEIs) of industrial chemical...

32 CFR 321.14 - DSS implementation policies.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.14 DSS implementation policies. (a) General... matters of particular concern to the Defense Security Service. (b) Privacy Act rules application. Any... 32 National Defense 2 2014-07-01 2014-07-01 false DSS implementation policies. 321.14 Section 321...

32 CFR 321.14 - DSS implementation policies.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.14 DSS implementation policies. (a) General... matters of particular concern to the Defense Security Service. (b) Privacy Act rules application. Any... 32 National Defense 2 2013-07-01 2013-07-01 false DSS implementation policies. 321.14 Section 321...

32 CFR 321.14 - DSS implementation policies.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.14 DSS implementation policies. (a) General... matters of particular concern to the Defense Security Service. (b) Privacy Act rules application. Any... 32 National Defense 2 2012-07-01 2012-07-01 false DSS implementation policies. 321.14 Section 321...

Chondrosarcoma of the Osseous Spine: An Analysis of Epidemiology, Patient Outcomes, and Prognostic Factors Using the SEER Registry From 1973 to 2012.

PubMed

Arshi, Armin; Sharim, Justin; Park, Don Y; Park, Howard Y; Bernthal, Nicholas M; Yazdanshenas, Hamed; Shamie, Arya N

2017-05-01

Retrospective analysis. To determine the epidemiology and prognostic indicators in patients with chondrosarcoma of the osseous spine. Chondrosarcoma of the spine is rare, with limited data on its epidemiology, clinicopathologic features, and treatment outcomes. Therapy centers on complete en bloc resection with radiotherapy reserved for subtotal resection or advanced disease. The Surveillance, Epidemiology, and End Results Registry was queried for patients with chondrosarcoma of the osseous spine from 1973 to 2012. Study variables included age, sex, race, year of diagnosis, size, grade, extent of disease, and treatment modality. The search identified 973 cases of spinal chondrosarcoma. Mean age at diagnosis was 51.6 years, and 627% of patients were males. Surgical resection and radiotherapy were performed in 75.2% and 21.3% of cases, respectively. Kaplan-Meier analysis demonstrated overall survival (OS) and disease-specific survival (DSS) of 53% and 64%, respectively, at 5 years. Multivariate Cox regression analysis showed that age (OS, P < 0.001; DSS, P = 0.007), grade (OS, P < 0.001; DSS, P < 0.001), surgical resection (OS, P < 0.001; DSS, P < 0.001), and extent of disease (OS, P < 0.001; DSS, P < 0.001) were independent survival determinants; tumor size was an independent predictor of OS (P = 0.006). For confined disease, age (P = 0.013), decade of diagnosis (P = 0.023), and surgery (P = 0.017) were independent determinants of OS. For locally invasive disease, grade (OS, P < 0.001; DSS, P = 0.003), surgery (OS, P = 0.013; DSS, P = 0.046), and size (OS, P = 0.001, DSS, P = 0.002) were independent determinants of OS and DSS. Radiotherapy was an independent indicator of worse OS for both confined (P = 0.004) and locally invasive disease (P = 0.002). For metastatic disease, grade (OS, P = 0.021; DSS, P = 0.012) and surgery (OS, P = 0.007; DSS, P = 0.004) were survival determinants for both OS and DSS, whereas radiotherapy predicted improved OS (P = 0.039). Surgical resection confers survival benefit in patients with chondrosarcoma of the spine independent of extent of disease. Radiotherapy improves survival in patients with metastatic disease and worsens outcomes in patients with confined and locally invasive disease. 4.

Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American Population-based Analysis.

PubMed

Hamilton, Sarah N; Ho, Cheryl; Laskin, Janessa; Zhai, Yongliang; Mak, Paul; Wu, Jonn

2016-12-01

The effect of ethnicity on nasopharyngeal cancer (NPC) outcomes is unclear. This retrospective analysis examines survival and the impact of concurrent chemoradiation (chemoRT) among Asian and non-Asian patients. Subjects included 380 consecutive patients with NPC treated at a Canadian institution from 2000 to 2009. Five-year Kaplan-Meier progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were compared between Asian (n=279) and non-Asian (n=101) subjects. Multivariable analysis was performed using Cox regression modeling. Two-variable interaction terms with concurrent chemoRT were used to examine whether concurrent chemoRT conferred different effects among subgroups. Asian subjects presented with earlier stage (P=0.005), were younger, had better performance status, and were less likely smokers (all P<0.001). Survival among Asian versus non-Asian subjects with stage I/II NPC were: PFS 68% versus 59% (P=0.04), DSS 87% versus 77% (P=0.08), and OS 84% versus 74% (P=0.003). Corresponding rates with stage III/IVA/IVB disease were PFS 49% versus 42% (P=0.12), DSS 72% versus 46% (P=0.001), and OS 70% versus 44% (P<0.001). On multivariable analysis, Asian ethnicity, age below 65 years, ECOG performance status 0-1, early stage, staging MRI use, and concurrent chemoRT were associated with improved DSS and OS (P<0.05). On testing interactions with concurrent chemoRT, Asian versus non-Asian ethnicity was significant (hazard ratio 3.9), suggesting that concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects. In this population-based study, Asian ethnicity was associated with improved DSS and OS. Concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects.

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

PubMed

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

2014-01-01

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

Omega 3 fatty acids supplementation has an ameliorative effect in experimental ulcerative colitis despite increased colonic neutrophil infiltration.

PubMed

Varnalidis, Ioannis; Ioannidis, Orestis; Karamanavi, Elisavet; Ampas, Zafeiris; Poutahidis, Theofilos; Taitzoglou, Ioannis; Paraskevas, George; Botsios, Dimitrios

2011-10-01

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

The effects of whole mushrooms during inflammation

PubMed Central

Yu, Sanhong; Weaver, Veronika; Martin, Keith; Cantorna, Margherita T

2009-01-01

Background Consumption of edible mushrooms has been suggested to improve health. A number of isolated mushroom constituents have been shown to modulate immunity. Five commonly consumed edible mushrooms were tested to determine whether whole mushrooms stimulate the immune system in vitro and in vivo. Results The white button (WB) extracts readily stimulated macrophage production of TNF-α. The crimini, maitake, oyster and shiitake extracts also stimulated TNF-α production in macrophage but the levels were lower than from WB stimulation. Primary cultures of murine macrophage and ovalbumin (OVA) specific T cells showed that whole mushroom extracts alone had no effect on cytokine production but co-stimulation with either lipopolysacharide or OVA (respectively) induced TNF-α, IFN-γ, and IL-1β while decreasing IL-10. Feeding mice diets that contained 2% WB mushrooms for 4 weeks had no effect on the ex vivo immune responsiveness or associated toxicity (changes in weight or pathology of liver, kidney and gastrointestinal tract). Dextran sodium sulfate (DSS) stimulation of mice that were fed 1% WB mushrooms were protected from DSS induced weight loss. In addition, 2% WB feeding protected the mice from transient DSS induced colonic injury. The TNF-α response in the colon and serum of the DSS challenged and 2% WB fed mice was higher than controls. Conclusion The data support a model whereby edible mushrooms regulate immunity in vitro. The in vivo effects of edible mushrooms required a challenge with DSS to detect small changes in TNF-α and transient protection from colonic injury. There are modest effects of in vivo consumption of edible mushrooms on induced inflammatory responses. The result is not surprising since it would certainly be harmful to strongly induce or suppress immune function following ingestion of a commonly consumed food. PMID:19232107

Alterations in melatonin and 5-HT signalling in the colonic mucosa of mice with dextran-sodium sulfate-induced colitis.

PubMed

MacEachern, Sarah J; Keenan, Catherine M; Papakonstantinou, Evangelia; Sharkey, Keith A; Patel, Bhavik Anil

2018-05-01

Inflammatory bowel disease (IBD) is characterized by pain, bleeding, cramping and altered gastrointestinal (GI) function. Changes in mucosal 5-HT (serotonin) signalling occur in animal models of colitis and in humans suffering from IBD. Melatonin is co-released with 5-HT from the mucosa and has a wide variety of actions in the GI tract. Here, we examined how melatonin signalling is affected by colitis and determined how this relates to 5-HT signalling. Using electroanalytical approaches, we investigated how 5-HT release, reuptake and availability as well as melatonin availability are altered in dextran sodium sulfate (DSS)-induced colitis in mice. Studies were conducted to explore if melatonin treatment during active colitis could reduce the severity of colitis. We observed an increase in 5-HT and a decrease in melatonin availability in DSS-induced colitis. A significant reduction in 5-HT reuptake was observed in DSS-induced colitis animals. A reduction in the content of 5-HT was observed, but no difference in tryptophan levels were observed. A reduction in deoxycholic acid-stimulated 5-HT availability and a significant reduction in mechanically-stimulated 5-HT and melatonin availability were observed in DSS-induced colitis. Orally or rectally administered melatonin once colitis was established did not significantly suppress inflammation. Our data suggest that DSS-induced colitis results in a reduction in melatonin availability and an increase in 5-HT availability, due to a reduction/loss of tryptophan hydroxylase 1 enzyme, 5-HT content and 5-HT transporters. Mechanosensory release was more susceptible to inflammation when compared with chemosensory release. © 2018 The British Pharmacological Society.

Bifidobacterium breve Attenuates Murine Dextran Sodium Sulfate-Induced Colitis and Increases Regulatory T Cell Responses

PubMed Central

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

2014-01-01

While some probiotics have shown beneficial effects on preventing or treating colitis development, others have shown no effects. In this study, we have assessed the immunomodulating effects of two probiotic strains, Lactobacillus rhamnosus (L. rhamnosus) and Bifidobacterium breve (B. breve) on T cell polarization in vitro, using human peripheral blood mononuclear cells (PBMC), and in vivo, using murine dextran sodium sulfate (DSS) colitis model. With respect to the latter, the mRNA expression of T cell subset-associated transcription factors and cytokines in the colon was measured and the T helper type (Th) 17 and regulatory T cell (Treg) subsets were determined in the Peyer's patches. Both L. rhamnosus and B. breve incubations in vitro reduced Th17 and increased Th2 cell subsets in human PBMCs. In addition, B. breve incubation was also able to reduce Th1 and increase Treg cell subsets in contrast to L. rhamnosus. In vivo intervention with B. breve, but not L. rhamnosus, significantly attenuated the severity of DSS-induced colitis. In DSS-treated C57BL/6 mice, intervention with B. breve increased the expression of mRNA encoding for Th2- and Treg-associated cytokines in the distal colon. In addition, intervention with B. breve led to increases of Treg and decreases of Th17 cell subsets in Peyer's patches of DSS-treated mice. B. breve modulates T cell polarization towards Th2 and Treg cell-associated responses in vitro and in vivo. In vivo B. breve intervention ameliorates DSS-induced colitis symptoms and this protective effect may mediated by its effects on the T-cell composition. PMID:24787575

Cost-utility analysis of an adjunctive recombinant activated factor VIIa for on-demand treatment of bleeding episodes in dengue haemorrhagic fever.

PubMed

Naing, Cho; Poovorawan, Yong; Mak, Joon Wah; Aung, Kyan; Kamolratankul, Pirom

2015-06-01

The present study aimed to assess the cost-utility analysis of using an adjunctive recombinant activated factor VIIa (rFVIIa) in children for controlling life-threatening bleeding in dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS). We constructed a decision-tree model, comparing a standard care and the use of an additional adjuvant rFVIIa for controlling life-threatening bleeding in children with DHF/DSS. Cost and utility benefit were estimated from the societal perspective. The outcome measure was cost per quality-adjusted life years (QALYs). Overall, treatment with adjuvant rFVIIa gained QALYs, but the total cost was higher. The incremental cost-utility ratio for the introduction of adjuvant rFVIIa was $4241.27 per additional QALY. Sensitivity analyses showed the utility value assigned for calculation of QALY was the most sensitive parameter. We concluded that despite high cost, there is a role for rFVIIa in the treatment of life-threatening bleeding in patients with DHF/DSS.

Near-Infrared Spectroscopy as an Analytical Process Technology for the On-Line Quantification of Water Precipitation Processes during Danhong Injection.

PubMed

Liu, Xuesong; Wu, Chunyan; Geng, Shu; Jin, Ye; Luan, Lianjun; Chen, Yong; Wu, Yongjiang

2015-01-01

This paper used near-infrared (NIR) spectroscopy for the on-line quantitative monitoring of water precipitation during Danhong injection. For these NIR measurements, two fiber optic probes designed to transmit NIR radiation through a 2 mm flow cell were used to collect spectra in real-time. Partial least squares regression (PLSR) was developed as the preferred chemometrics quantitative analysis of the critical intermediate qualities: the danshensu (DSS, (R)-3, 4-dihydroxyphenyllactic acid), protocatechuic aldehyde (PA), rosmarinic acid (RA), and salvianolic acid B (SAB) concentrations. Optimized PLSR models were successfully built and used for on-line detecting of the concentrations of DSS, PA, RA, and SAB of water precipitation during Danhong injection. Besides, the information of DSS, PA, RA, and SAB concentrations would be instantly fed back to site technical personnel for control and adjustment timely. The verification experiments determined that the predicted values agreed with the actual homologic value.

A Case Study: Climate Change Decision Support for the Apalachicola, Chattahoochee, Flint Basins

NASA Astrophysics Data System (ADS)

Day, G. N.; McMahon, G.; Friesen, N.; Carney, S.

2011-12-01

Riverside Technology, inc. has developed a Climate Change Decision Support System (DSS) to provide water managers with a tool to explore a range of current Global Climate Model (GCM) projections to evaluate their potential impacts on streamflow and the reliability of future water supplies. The system was developed as part of a National Oceanic and Atmospheric Administration (NOAA) Small Business Innovation Research (SBIR) project. The DSS uses downscaled GCM data as input to small-scale watershed models to produce time series of projected undepleted streamflow for various emission scenarios and GCM simulations. Until recently, water managers relied on historical streamflow data for water resources planning. In many parts of the country, great effort has been put into estimating long-term historical undepleted streamflow accounting for regulation, diversions, and return flows to support planning and water rights administration. In some cases, longer flow records have been constructed using paleohydrologic data in an attempt to capture climate variability beyond what is evident during the observed historical record. Now, many water managers are recognizing that historical data may not be representative of an uncertain climate future, and they have begun to explore the use of climate projections in their water resources planning. The Climate Change DSS was developed to support water managers in planning by accounting for both climate variability and potential climate change. In order to use the information for impact analysis, the projected streamflow time series can be exported and substituted for the historical streamflow data traditionally applied in their system operations models for water supply planning. This paper presents a case study in which climate-adjusted flows are coupled with the U.S. Army Corps of Engineers (USACE) ResSim model for the Apalachicola, Chattahoochee, and Flint (ACF) River basins. The study demonstrates how climate scenarios can be used with existing or proposed operating rules to explore the range of potential climate impacts on lake levels, drought trigger frequency, hydropower generation, and low-flow statistics. Initial system implementation of the Climate Change DSS was focused in the State of Colorado working with water supply agencies in the Front Range to assess local water supply vulnerability to climate change. To facilitate national implementation, the system capitalizes on National Weather Service (NWS) watershed models currently used for operational river forecasting. These models are well calibrated and available for the entire country. The system has been extended to include the ACF and the Sacramento River basins because of the importance of the water resources in these basins. Plans are now being made to expand coverage to include the Baltimore-Washington, D.C. water supply area. The DSS is operational and publicly available (www.climatechangedss.com).

Group velocity locked vector dissipative solitons in a high repetition rate fiber laser

NASA Astrophysics Data System (ADS)

Luo, Yiyang; Li, Lei; Liu, Deming; Sun, Qizhen; Wu, Zhichao; Xu, Zhilin; Tang, Dingyuan; Fu, Songnian; Zhao, Luming

2016-08-01

Vectorial nature of dissipative solitons (DSs) with high repetition rates is studied for the first time in a normal-dispersion fiber laser. Despite the fact that the formed DSs are strongly chirped and the repetition rate is greater than 100 MHz, polarization locked and polarization rotating group velocity locked vector DSs can be formed under 129.3 MHz fundamental mode-locking and 258.6 MHz harmonic mode-locking of the fiber laser, respectively. The two orthogonally polarized components of these vector DSs possess distinctly different central wavelengths and travel together at the same group velocity in the laser cavity, resulting in a gradual spectral edge and small steps on the optical spectra, which can be considered as an auxiliary indicator of the group velocity locked vector DSs.

Disease-specific survival following the brachytherapy management of prostate cancer.

PubMed

Stock, Richard G; Cesaretti, Jamie A; Stone, Nelson N

2006-03-01

To determine disease-specific survival (DSS) and associated predictive factors after prostate brachytherapy. A total of 1561 patients underwent brachytherapy for prostate cancer from 1990 to 2004 (median follow-up, 3.8 years). Treatment included brachytherapy alone (n = 634), brachytherapy and hormonal therapy (n = 420), and implant and external beam therapy (n = 507). The DSS and overall survival rates at 10 years were 96% and 74%, respectively. Gleason score significantly impacted DSS, with 10-year rates of 98%, 91%, and 92% for scores of < or = 6, 7, and > or = 8, respectively (p < 0.0001). Multivariate analysis revealed that PSA status after treatment had the most significant effect on DSS. Ten-year DSS rates were 100%, 52%, and 98%, respectively for patients without PSA failure (n = 1430), failure with a doubling time (DT) < or = 10 months (n = 64), and failure with a DT > 10 months (n = 67), respectively (p < 0.0001). In patients with PSA failure, DSS rates were 30%, 67%, and 98%, for those with DT < or = 6 months, > 6-10 months, and > 10 months, respectively (p < 0.0001). The 10-year DSS rate supports the efficacy of brachytherapy. Patients dying with disease within 10 years after treatment harbor inherently aggressive cancer with high Gleason scores and short DT.

Cardioprotective Effect of Danshensu against Ischemic/Reperfusion Injury via c-Subunit of ATP Synthase Inhibition

PubMed Central

Zhao, JingYi; Fan, Zixuan; Bao, Jiadi; Sun, Dawei; Sun, Chun

2017-01-01

Mitochondrial permeability transition pore (MPTP) opening is the main culprit of ischemic/reperfusion (IR) injury. It is reported that c-subunit of ATP synthase is the core component of MPTP. Danshensu (DSS), a monomer isolated from the traditional Chinese herb Danshen, has showed cardioprotective effect against IR injury through unknown mechanism. In this study, rat hearts were suspended in Langendorff instrument and perfused with Krebs-Henseleit (KH) buffer containing DSS for 60 minutes, followed by 30 minutes of global ischemia. Parameters including heart rate, left ventricular developed pressure, and the rate of left ventricle diastolic pressure change were recorded to assess their cardiac function. All these indexes were improved in DSS group. The rate of cardiomyocytes apoptosis and MPTP opening were both inhibited in DSS group. In addition, DSS administration leads to downregulation of c-subunit of ATP synthase in both mRNA and protein levels. Consistently, when c-subunit of ATP synthase was overexpressed in H9C2 cells through pcDNA3/5G1 plasmid transfection, MPTP opening was enhanced when the cardioprotective effect of DSS also tapers. In conclusion, DSS could alleviate cardiac IR injury via inhibiting c-subunit of ATP synthase expression. PMID:29250127

Lactobacillus reuteri Maintains a Functional Mucosal Barrier during DSS Treatment Despite Mucus Layer Dysfunction

PubMed Central

Willing, Ben; Petersson, Joel; Rang, Sara; Phillipson, Mia; Holm, Lena; Roos, Stefan

2012-01-01

Treatment with the probiotic bacterium Lactobacillus reuteri has been shown to prevent dextran sodium sulfate (DSS)-induced colitis in rats. This is partly due to reduced P-selectin-dependent leukocyte- and platelet-endothelial cell interactions, however, the mechanism behind this protective effect is still unknown. In the present study a combination of culture dependent and molecular based T-RFLP profiling was used to investigate the influence of L. reuteri on the colonic mucosal barrier of DSS treated rats. It was first demonstrated that the two colonic mucus layers of control animals had different bacterial community composition and that fewer bacteria resided in the firmly adherent layer. During DSS induced colitis, the number of bacteria in the inner firmly adherent mucus layer increased and bacterial composition of the two layers no longer differed. In addition, induction of colitis dramatically altered the microbial composition in both firmly and loosely adherent mucus layers. Despite protecting against colitis, treatment with L. reuteri did not improve the integrity of the mucus layer or prevent distortion of the mucus microbiota caused by DSS. However, L. reuteri decreased the bacterial translocation from the intestine to mesenteric lymph nodes during DSS treatment, which might be an important part of the mechanisms by which L. reuteri ameliorates DSS induced colitis. PMID:23029509

Anticipating on amplifying water stress: Optimal crop production supported by anticipatory water management

NASA Astrophysics Data System (ADS)

Bartholomeus, Ruud; van den Eertwegh, Gé; Simons, Gijs

2015-04-01

Agricultural crop yields depend largely on the soil moisture conditions in the root zone. Drought but especially an excess of water in the root zone and herewith limited availability of soil oxygen reduces crop yield. With ongoing climate change, more prolonged dry periods alternate with more intensive rainfall events, which changes soil moisture dynamics. With unaltered water management practices, reduced crop yield due to both drought stress and waterlogging will increase. Therefore, both farmers and water management authorities need to be provided with opportunities to reduce risks of decreasing crop yields. In The Netherlands, agricultural production of crops represents a market exceeding 2 billion euros annually. Given the increased variability in meteorological conditions and the resulting larger variations in soil moisture contents, it is of large economic importance to provide farmers and water management authorities with tools to mitigate risks of reduced crop yield by anticipatory water management, both at field and at regional scale. We provide the development and the field application of a decision support system (DSS), which allows to optimize crop yield by timely anticipation on drought and waterlogging situations. By using this DSS, we will minimize plant water stress through automated drainage and irrigation management. In order to optimize soil moisture conditions for crop growth, the interacting processes in the soil-plant-atmosphere system need to be considered explicitly. Our study comprises both the set-up and application of the DSS on a pilot plot in The Netherlands, in order to evaluate its implementation into daily agricultural practice. The DSS focusses on anticipatory water management at the field scale, i.e. the unit scale of interest to a farmer. We combine parallel field measurements ('observe'), process-based model simulations ('predict'), and the novel Climate Adaptive Drainage (CAD) system ('adjust') to optimize soil moisture conditions. CAD is used both for controlled drainage practices and for sub-irrigation. The DSS has a core of the plot-scale SWAP model (soil-water-atmosphere-plant), extended with a process-based module for the simulation of oxygen stress for plant roots. This module involves macro-scale and micro-scale gas diffusion, as well as the plant physiological demand of oxygen, to simulate transpiration reduction due to limited oxygen availability. Continuous measurements of soil moisture content, groundwater level, and drainage level are used to calibrate the SWAP model each day. This leads to an optimal reproduction of the actual soil moisture conditions by data assimilation in the first step in the DSS process. During the next step, near-future (+10 days) soil moisture conditions and drought and oxygen stress are predicted using weather forecasts. Finally, optimal drainage levels to minimize stress are simulated, which can be established by CAD. Linkage to a grid-based hydrological simulation model (SPHY) facilitates studying the spatial dynamics of soil moisture and associated implications for management at the regional scale. Thus, by using local-scale measurements, process-based models and weather forecasts to anticipate on near-future conditions, not only field-scale water management but also regional surface water management can be optimized both in space and time.

Curcuma longa extract exerts a myorelaxant effect on the ileum and colon in a mouse experimental colitis model, independent of the anti-inflammatory effect.

PubMed

Aldini, Rita; Budriesi, Roberta; Roda, Giulia; Micucci, Matteo; Ioan, Pierfranco; D'Errico-Grigioni, Antonia; Sartini, Alessandro; Guidetti, Elena; Marocchi, Margherita; Cevenini, Monica; Rosini, Francesca; Montagnani, Marco; Chiarini, Alberto; Mazzella, Giuseppe

2012-01-01

Curcuma has long been used as an anti-inflammatory agent in inflammatory bowel disease. Since gastrointestinal motility is impaired in inflammatory states, the aim of this work was to evaluate if Curcuma Longa had any effect on intestinal motility. The biological activity of Curcuma extract was evaluated against Carbachol induced contraction in isolated mice intestine. Acute and chronic colitis were induced in Balb/c mice by Dextran Sulphate Sodium administration (5% and 2.5% respectively) and either Curcuma extract (200 mg/kg/day) or placebo was thereafter administered for 7 and 21 days respectively. Spontaneous contractions and the response to Carbachol and Atropine of ileum and colon were studied after colitis induction and Curcuma administration. Curcuma extract reduced the spontaneous contractions in the ileum and colon; the maximal response to Carbachol was inhibited in a non-competitive and reversible manner. Similar results were obtained in ileum and colon from Curcuma fed mice. DSS administration decreased the motility, mainly in the colon and Curcuma almost restored both the spontaneous contractions and the response to Carbachol after 14 days assumption, compared to standard diet, but a prolonged assumption of Curcuma decreased the spontaneous and Carbachol-induced contractions. Curcuma extract has a direct and indirect myorelaxant effect on mouse ileum and colon, independent of the anti-inflammatory effect. The indirect effect is reversible and non-competitive with the cholinergic agent. These results suggest the use of curcuma extract as a spasmolytic agent.

The use of AQUATOOL DSS applied to the System of Environmental-Economic Accounting for Water (SEEAW)

NASA Astrophysics Data System (ADS)

Pedro-Monzonís, María; Jiménez-Fernández, Pedro; Solera, Abel; Jiménez-Gavilán, Pablo

2016-02-01

Currently, water accounts are one of the next steps to be implemented in European River Basin Management Plans. Building water accounts is a complex task, mainly due to the lack of common European definitions and procedures. For their development, when data is not systematically measured, simulation models and estimations are necessary. The main idea of this paper is to present a new approach which enables the combined use of hydrological models and water resources models developed with AQUATOOL Decision Support System (DSS) to fill in the physical water supply and use tables and the asset accounts presented in the System of Economic and Environmental Accounts for Water (SEEAW). The case study is the Vélez River Basin, located in the southern part of the Iberian Peninsula in Spain. In addition to obtaining the physical water supply and use tables and the asset accounts in this river basin, we present here the indicators as a result thereof. These indicators cover many critical aspects of water management, showing a general description of the river basin and allowing decision-makers to characterise the pressures on water resources. As a general conclusion, the union of AQUATOOL DSS and SEEAW will provide more complete information to decision-makers and it enables to introduce these methodological decisions in order to guarantee consistency and comparability of the results between different river basins.

Expression status and prognostic significance of mammalian target of rapamycin pathway members in urothelial carcinoma of urinary bladder after cystectomy.

PubMed

Schultz, Luciana; Albadine, Roula; Hicks, Jessica; Jadallah, Sana; DeMarzo, Angelo M; Chen, Ying-Bei; Nielsen, Matthew E; Neilsen, Matthew E; Gonzalgo, Mark L; Sidransky, David; Schoenberg, Mark; Netto, George J

2010-12-01

Bladder urothelial carcinoma has high rates of mortality and morbidity. Identifying novel molecular prognostic factors and targets of therapy is crucial. Mammalian target of rapamycin (mTOR) pathway plays a pivotal role in establishing cell shape, migration, and proliferation. Tissue microarrays were constructed from 132 cystectomies (1994-2002). Immunohistochemistry was performed for Pten, c-myc, p27, phosphorylated (phos)Akt, phosS6, and 4E-BP1. Markers were evaluated for pattern, percentage, and intensity of staining. Mean length of follow-up was 62.6 months (range, 1-182 months). Disease progression, overall survival (OS), and disease-specific survival (DSS) rates were 42%, 60%, and 68%, respectively. Pten showed loss of expression in 35% of bladder urothelial carcinoma. All markers showed lower expression in invasive bladder urothelial carcinoma compared with benign urothelium with the exception of 4E-BP1. Pten, p27, phosAkt, phosS6, and 4E-BP1 expression correlated with pathologic stage (pathological stage; P<.03). Pten, 4E-BP1, and phosAkt expression correlated with divergent aggressive histology and invasion. phosS6 expression inversely predicted OS (P=.01), DSS (P=.001), and progression (P=.05). c-myc expression inversely predicted progression (P=.01). In a multivariate analysis model that included TNM stage grouping, divergent aggressive histology, concomitant carcinoma in situ, phosS6, and c-myc expression, phosS6 was an independent predictor of DSS (P=.03; hazard ratio [HR], -0.19), whereas c-myc was an independent predictor of progression (P=.02; HR, -0.38). In a second model substituting organ-confined disease and lymph node status for TNM stage grouping, phosS6 and c-myc remained independent predictors of DSS (P=.03; HR, -0.21) and progression (P=.03; HR, -0.34), respectively. We found an overall down-regulation of mTOR pathway in bladder urothelial carcinoma. phosS6 independently predicted DSS, and c-myc independently predicted progression. Copyright © 2010 American Cancer Society.

Carvacrol exhibits anti-oxidant and anti-inflammatory effects against 1, 2-dimethyl hydrazine plus dextran sodium sulfate induced inflammation associated carcinogenicity in the colon of Fischer 344 rats.

PubMed

Arigesavan, Kaninathan; Sudhandiran, Ganapasam

2015-05-29

Chronic inflammation is one of the remarkable etiologic factors for various human ailments including cancer. The well known hypothesis is that persistent inflammation in colon can increase the risk of colorectal cancer (CRC). In this study, a pharmacological evaluation of carvacrol, a phenolic monoterpene constituent of essential oils produced from aromatic plant Oreganum vulgarea sp. on colitis associated colon cancer (CACC) induced by 1,2 Dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) in male Fischer 344 rat model was studied. F344 rats were given three subcutaneous injections of DMH (40 mg/kg body wt) in the first week and were given free access to drinking water containing 1% DSS for the next one week followed by 7-14 days of water as three cycles. Carvacrol was administrated before and after tumor induction at a concentration of 50 mg/kg body weight (o.p). Carvacrol treated groups promotes the endogenous antioxidant system and suppress the inflammation in DMH/DSS induced animals. An increased antioxidant status and restoration of histological lesions in the inflamed colonic mucosa was observed in carvacrol treated rats. This effect was confirmed biochemically by reducing free-radical accumulation and suppressing expression of pro-inflammatory mediators. In this study, Carvacrol significantly increased the anti-oxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) glutathione (GSH) levels and reduced lipid peroxides (LPO), myeloperoxidase (MPO) and nitric oxide (NO) as compared to DMH/DSS induced rats. These dramatic changes facilitate the suppression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), and interleukin-1 beta (IL-1β) in CACC induced rats. Taken together, these findings suggest that Carvacrol may play a beneficial role in DMH/DSS induced experimental rat model and serve as an excellent dietary antioxidant as well as anti-inflammatory agent. It may represent novel therapeutic interventions against colon cancer triggered by chronic inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Histological assessment of cervical lymph node identifies patients with head and neck squamous cell carcinoma (HNSCC): who would benefit from chemoradiation after surgery?

PubMed

Wan, Xiao Chloe; Egloff, Ann Marie; Johnson, Jonas

2012-12-01

Postoperative chemoradiation (CRT) has been shown to be more effective than postoperative radiotherapy (RT) alone in high risk head and neck squamous cell carcinoma (HNSCC) patients. Multimodality therapy is associated with more treatment related-toxicity. In this study, we assessed cervical lymph node histological characteristics to detect prognostic and predictive value differences to help guide therapeutic decision making. Retrospective analysis of Cancer Registry data. HNSCC surgical patients who had tumor resection and neck dissection at our institution from 1980 to 2008 were identified (n=1510). Multivariable Cox proportional hazards regression models were developed to identify significant predictors of three outcomes: overall survival (OS), disease-specific survival (DSS), and neck disease recurrence (NDR). Hazard ratios were estimated for the number of cervical nodal metastases and presence of extracapsular spread (ECS) by adjuvant treatment after controlling for significant covariates. Increasing number of positive nodes was significantly associated with poorer outcomes in OS, DSS, and NDR models (p<0.0001, p<0.0001, p=0.0002, respectively). OS and DSS associated with adjuvant treatment (none, RT, or CRT) were modified by number of positive nodes, ECS status, and cancer site. The presence of ECS was associated with reduced OS and DSS (p=0.077, p=0.001 respectively), but not significantly associated with NDR (p=0.179). Nodal positive patients benefited from adjuvant therapy regardless of ECS status. CRT consistently conferred a survival advantage over RT across all nodal categories, although the difference was not statistically significant. We observed a consistent survival advantage with CRT over RT for patients with positive cervical nodal metastasis, although the difference was not statistically significant. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

PubMed

Muller, Julius; Parizotto, Eneida; Antrobus, Richard; Francis, James; Bunce, Campbell; Stranks, Amanda; Nichols, Marshall; McClain, Micah; Hill, Adrian V S; Ramasamy, Adaikalavan; Gilbert, Sarah C

2017-06-08

Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis. Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h post challenge was profiled on Illumina HT12v4 microarrays. Changes in gene expression most strongly correlated with DSS were selected to train a Random Forest model and tested on two independent test sets consisting of 41 individuals profiled on a different microarray platform and 33 volunteers assayed by qRT-PCR. 1456 probes are significantly associated with DSS at 1% false discovery rate. We selected 19 genes with the largest fold change to train a random forest model. We observed good concordance between predicted and actual scores in the first test set (r = 0.57; RMSE = -16.1%) with the greatest agreement achieved on samples collected approximately 72 h post challenge. Therefore, we assayed samples collected at baseline and 72 h post challenge in the second test set by qRT-PCR and observed good concordance (r = 0.81; RMSE = -36.1%). We developed a 19-gene qRT-PCR panel to predict DSS, validated on two independent datasets. A transcriptomics based panel could provide a more objective measure of symptom scoring in future influenza challenge studies. Trial registration Samples were obtained from a clinical trial with the ClinicalTrials.gov Identifier: NCT02014870, first registered on December 5, 2013.

Heterogeneity of (18)F-FDG PET combined with expression of EGFR may improve the prognostic stratification of advanced oropharyngeal carcinoma.

PubMed

Wang, Hung-Ming; Cheng, Nai-Ming; Lee, Li-Yu; Fang, Yu-Hua Dean; Chang, Joseph Tung-Chieh; Tsan, Din-Li; Ng, Shu-Hang; Liao, Chun-Ta; Yang, Lan-Yan; Yen, Tzu-Chen

2016-02-01

The Ang's risk profile (based on p16, smoking and cancer stage) is a well-known prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC). Whether heterogeneity in (18)F-fluorodeoxyglucose (FDG) positron emission tomographic (PET) images and epidermal growth factor receptor (EGFR) expression could provide additional information on clinical outcomes in advanced-stage OPSCC was investigated. Patients with stage III-IV OPSCC who completed primary therapy were eligible. Zone-size nonuniformity (ZSNU) extracted from pretreatment FDG PET scans was used as an index of image heterogeneity. EGFR and p16 expression were examined by immunohistochemistry. Disease-specific survival (DSS) and overall survival (OS) served as outcome measures. Kaplan-Meier estimates and Cox proportional hazards regression models were used for survival analysis. A bootstrap resampling technique was applied to investigate the stability of outcomes. Finally, a recursive partitioning analysis (RPA)-based model was constructed. A total of 113 patients were included, of which 28 were p16-positive. Multivariate analysis identified the Ang's profile, EGFR and ZSNU as independent predictors of both DSS and OS. Using RPA, the three risk factors were used to devise a prognostic scoring system that successfully predicted DSS in both p16-positive and -negative cases. The c-statistic of the prognostic index for DSS was 0.81, a value which was significantly superior to both AJCC stage (0.60) and the Ang's risk profile (0.68). In patients showing an Ang's high-risk profile (N = 77), the use of our scoring system clearly identified three distinct prognostic subgroups. It was concluded that a novel index may improve the prognostic stratification of patients with advanced-stage OPSCC. © 2015 UICC.

The prediction of drug metabolism, tissue distribution, and bioavailability of 50 structurally diverse compounds in rat using mechanism-based absorption, distribution, and metabolism prediction tools.

PubMed

De Buck, Stefan S; Sinha, Vikash K; Fenu, Luca A; Gilissen, Ron A; Mackie, Claire E; Nijsen, Marjoleen J

2007-04-01

The aim of this study was to assess a physiologically based modeling approach for predicting drug metabolism, tissue distribution, and bioavailability in rat for a structurally diverse set of neutral and moderate-to-strong basic compounds (n = 50). Hepatic blood clearance (CL(h)) was projected using microsomal data and shown to be well predicted, irrespective of the type of hepatic extraction model (80% within 2-fold). Best predictions of CL(h) were obtained disregarding both plasma and microsomal protein binding, whereas strong bias was seen using either blood binding only or both plasma and microsomal protein binding. Two mechanistic tissue composition-based equations were evaluated for predicting volume of distribution (V(dss)) and tissue-to-plasma partitioning (P(tp)). A first approach, which accounted for ionic interactions with acidic phospholipids, resulted in accurate predictions of V(dss) (80% within 2-fold). In contrast, a second approach, which disregarded ionic interactions, was a poor predictor of V(dss) (60% within 2-fold). The first approach also yielded accurate predictions of P(tp) in muscle, heart, and kidney (80% within 3-fold), whereas in lung, liver, and brain, predictions ranged from 47% to 62% within 3-fold. Using the second approach, P(tp) prediction accuracy in muscle, heart, and kidney was on average 70% within 3-fold, and ranged from 24% to 54% in all other tissues. Combining all methods for predicting V(dss) and CL(h) resulted in accurate predictions of the in vivo half-life (70% within 2-fold). Oral bioavailability was well predicted using CL(h) data and Gastroplus Software (80% within 2-fold). These results illustrate that physiologically based prediction tools can provide accurate predictions of rat pharmacokinetics.

Chemical characteristics of atmospheric PM2.5 loads during air pollution episodes in Giza, Egypt

NASA Astrophysics Data System (ADS)

Hassan, Salwa K.; Khoder, Mamdouh I.

2017-02-01

Several types of pollution episodes, including dust storm (DSs), haze dust (HDs), straw rice combustions (SRCs) are common phenomena and represent severe environmental hazard in Egypt. This study provides the first comprehensive analysis of the chemical characteristics of aerosol during air pollution episodes at an urban area in Giza, Egypt. PM2.5 samples during various PM episodes during 2013-2014 were collected and analyzed. Results indicate that the highest PM2.5 mass concentrations were found during DSs (250 μg/m3), followed by HDs (130 μg/m3) and SRCs (103 μg/m3). Average PM2.5 mass concentrations were 1.91, 3.68 and 1.68 times higher than on normal days (NDs) during HDs, DSs and SRCs, respectively. The highest total water-soluble ions concentration was 61.1 μg/m3 during HDs, followed by SRCs (41.9 μg/m3) and DSs (35.2 μg/m3). SO42- is the most abundant chemical components on the three PM episodes. Secondary inorganic ions (NO3-, SO42-, and NH4+) were enriched during HDs. The total secondary inorganic ions concentrations were 3.17, 1.39 and 1.75 times higher than NDs during HDs days, DSs days and SRCs days, respectively. PM from SRCs showed high K+ and Cl-. SO42-/K+, NO3-/SO42- and Cl-/K+ ratios proved effective as indicators for different pollution episodes. A Ca2+/Al ratio indicates that soil dust was dominant during DSs. Ion balance calculations indicated that PM2.5 from HDs was acidic, while the DSs and SRCs particles were alkaline and the NDs particle's was nearly neutral. The total crustal and anthropogenic metals concentrations were higher in DSs than other PM episodes and normal days. The enrichment factors values in PM episodes and normal days indicate that Fe and Mn in NDs, HDs, DSs and SRCs as well as Cr and Ni in DSs come mainly from crustal sources, whereas Cr, Ni, Co, Cu, Zn, Pb and Cd in PM episodes and NDs are anthropogenic.

Formal analysis of the surgical pathway and development of a new software tool to assist surgeons in the decision making in primary breast surgery.

PubMed

Catanuto, Giuseppe; Pappalardo, Francesco; Rocco, Nicola; Leotta, Marco; Ursino, Venera; Chiodini, Paolo; Buggi, Federico; Folli, Secondo; Catalano, Francesca; Nava, Maurizio B

2016-10-01

The increased complexity of the decisional process in breast cancer surgery is well documented. With this study we aimed to create a software tool able to assist patients and surgeons in taking proper decisions. We hypothesized that the endpoints of breast cancer surgery could be addressed combining a set of decisional drivers. We created a decision support system software tool (DSS) and an interactive decision tree. A formal analysis estimated the information gain derived from each feature in the process. We tested the DSS on 52 patients and we analyzed the concordance of decisions obtained by different users and between the DSS suggestions and the actual surgery. We also tested the ability of the system to prevent post breast conservation deformities. The information gain revealed that patients preferences are the root of our decision tree. An observed concordance respectively of 0.98 and 0.88 was reported when the DSS was used twice by an expert operator or by a newly trained operator vs. an expert one. The observed concordance between the DSS suggestion and the actual decision was 0.69. A significantly higher incidence of post breast conservation defects was reported among patients who did not follow the DSS decision (Type III of Fitoussi, N = 4; 33.3%, p = 0.004). The DSS decisions can be reproduced by operators with different experience. The concordance between suggestions and actual decision is quite low, however the DSS is able to prevent post- breast conservation deformities. Copyright © 2016 Elsevier Ltd. All rights reserved.

β-Glucans in food modify colonic microflora by inducing antimicrobial protein, calprotectin, in a Dectin-1-induced-IL-17F-dependent manner.

PubMed

Kamiya, T; Tang, C; Kadoki, M; Oshima, K; Hattori, M; Saijo, S; Adachi, Y; Ohno, N; Iwakura, Y

2018-05-01

Dectin-1 (gene symbol: Clec7a) is a receptor for β-glucans that play an important role for the host defense against fungi. Recently, we showed that Clec7a -/- mice are resistant against dextran sodium sulfate (DSS)-induced colitis because of regulatory T-cell population expansion in the colon. The regulatory T-cell expansion is caused by expansion of commensal Lactobacillus murinus whose growth is suppressed by an antimicrobial protein, calprotectin S100A8/A9. In this report, we showed that S100A8 was mainly produced by mouse colonic epithelial cells. S100A8 was not induced directly by Dectin-1 but by Dectin-1-induced cytokines, especially interleukin-17F (IL-17F), that were produced by several types of innate immune cells including CD11c + /CD11b + myeloid cells in colonic lamina propria. S100A8/A9 heterodimer preferentially suppressed the growth of L. murinus that was increased in both Clec7a -/- and Il17f -/- mice. Furthermore, similar expansion of L. murinus and DSS-colitis resistance were observed in mice fed with β-glucan-free food. These observations suggest that food-derived β-glucans control the specific commensal microbiota via the Dectin-1-IL-17F-calprotectin axis to maintain the intestinal homeostasis.

Decision support system for drinking water management

NASA Astrophysics Data System (ADS)

Janža, M.

2012-04-01

The problems in drinking water management are complex and often solutions must be reached under strict time constrains. This is especially distinct in case of environmental accidents in the catchment areas of the wells that are used for drinking water supply. The beneficial tools that can help decision makers and make program of activities more efficient are decision support systems (DSS). In general they are defined as computer-based support systems that help decision makers utilize data and models to solve unstructured problems. The presented DSS was developed in the frame of INCOME project which is focused on the long-term stable and safe drinking water supply in Ljubljana. The two main water resources Ljubljana polje and Barje alluvial aquifers are characterized by a strong interconnection of surface and groundwater, high vulnerability, high velocities of groundwater flow and pollutant transport. In case of sudden pollution, reactions should be very fast to avoid serious impact to the water supply. In the area high pressures arising from urbanization, industry, traffic, agriculture and old environmental burdens. The aim of the developed DSS is to optimize the activities in cases of emergency water management and to optimize the administrative work regarding the activities that can improve groundwater quality status. The DSS is an interactive computer system that utilizes data base, hydrological modelling, and experts' and stakeholders' knowledge. It consists of three components, tackling the different abovementioned issues in water management. The first one utilizes the work on identification, cleaning up and restoration of illegal dumpsites that are a serious threat to the qualitative status of groundwater. The other two components utilize the predictive capability of the hydrological model and scenario analysis. The user interacts with the system by a graphical interface that guides the user step-by-step to the recommended remedial measures. Consequently, the acquisition of information to support the water management's decisions is simplified and faster, thus contributing to more efficient water management and a safer supply of drinking water.

Evaluation of Gastrointestinal Leakage in Multiple Enteric Inflammation Models in Chickens

PubMed Central

Kuttappan, Vivek A.; Vicuña, Eduardo A.; Latorre, Juan D.; Wolfenden, Amanda D.; Téllez, Guillermo I.; Hargis, Billy M.; Bielke, Lisa R.

2015-01-01

Enteric inflammation models can help researchers’ study methods to improve health and performance and evaluate various growth promoters and dietary formulations targeted to improve performance in poultry. Oral administration of fluorescein isothiocyanate-dextran (FITC-d; 3–5 kDa) and its pericellular mucosal epithelial leakage are an established marker to evaluate enteric inflammation in multiple species. The present study evaluated different methods to induce gut inflammation in poultry based on FITC-d leakage. Four independent experiments were completed with different inflammation treatment groups, and serum FITC-d and/or retention of FITC-d in GI tract were determined. In experiment 1 (n = 10 birds/treatment, broilers, processed at 14 days), groups included control (CON), dextran sodium sulfate (DSS; drinking water at 0.75%) and feed restriction (FRS; 24 h before processing). Experiment 2 (n = 14 birds/treatment, leghorns, processed at 7 days) included CON, DSS, FRS, and rye-based diet (RBD). In experiments 3 and 4 (n = 15 birds/treatment, broilers, processed at 7 days), groups were CON, DSS, high fat diet (HFD), FRS, and RBD. In all experiments, FRS and RBD treatments showed significantly higher serum FITC-d levels compared to the respective CON. This indicates that FRS and RBD results in disruption of the intact barrier of the gastrointestinal tract (GIT), resulting in increased gut permeability. DSS and HFD groups showed elevation of serum FITC-d levels although the magnitude of difference from respective CON was inconsistent between experiments. FRS was the only treatment which consistently showed elevated retention of FITC-d in GIT in all experiments. The results from present studies showed that FRS and RBD, based on serum FITC-d levels, can be robust models to induce gut leakage in birds in different age and species/strains. PMID:26697435

Magnolol, a Natural Polyphenol, Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice.

PubMed

Zhao, Ling; Xiao, Hai-Tao; Mu, Huai-Xue; Huang, Tao; Lin, Ze-Si; Zhong, Linda L D; Zeng, Guang-Zhi; Fan, Bao-Min; Lin, Cheng-Yuan; Bian, Zhao-Xiang

2017-07-20

Magnolol is a lignan with anti-inflammatory activity identified in Magnolia officinalis . Ulcerative colitis (UC), one of the types of inflammatory bowel disease (IBD), is a disease that causes inflammation and ulcers in the colon. To investigate the effect of magnolol in dextran sulfate sodium (DSS)-induced experimental UC model, male C57 mice were treated with 2% DSS drinking water for 5 consecutive days followed by intragastric administration with magnolol (5, 10 and 15 mg/kg) daily for 7 days. The results showed that magnolol significantly attenuated disease activity index, inhibited colonic shortening, reduced colonic lesions and suppressed myeloperoxidase (MPO) activity. Moreover, colonic pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) induced by colitis were dramatically decreased by magnolol. To further unveil the metabolic signatures upon magnolol treatment, mass spectrometry-based metabolomic analysis of the small molecular metabolites in mice serum were performed. Compared with controls, abnormality of serum metabolic phenotypes in DSS-treated mice were effectively reversed by different doses of magnolol. In particular, magnolol treatment effectively elevated the serum levels of tryptophan metabolites including kynurenic acid (KA), 5-hydroxyindoleacetic acid, indoleacetic acid (IAA), indolelactic acid and indoxylsulfuric acid, which are potential aryl hydrocarbon receptor (AHR) ligands to impact colitis. These findings suggest that magnolol exerts anti-inflammatory effect on DSS-induced colitis and its underlying mechanisms are associated with the restoring of tryptophan metabolites that inhibit the colonic inflammation.

N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice.

PubMed

Amrouche-Mekkioui, Ilhem; Djerdjouri, Bahia

2012-09-15

The effect of N-acetylcysteine (NAC), a pharmacological antioxidant was investigated in a murine model of chronic colitis. Male NMRI mice were given 5% dextran sulfate sodium (DSS) in drinking water for 5 days followed by 10 days of water, three times. Compared to control mice given water, DSS-treated mice displayed severe imbalanced redox status with decreased glutathione and catalase, but increased malondialdehyde, protein carbonyls, nitric oxide and myeloperoxidase levels, at days 35th (active colitis) and 45th (recovery period). It also resulted in mitochondrial dysfunction, mucosal ulcers, mucin-depleted crypts and epithelial cell apoptosis. Crypt abscesses and glandular hyperplasia occurred selectively in distal colon. NAC (150 mg/kg) given in drinking water for 45 days along with 3 DSS cycles improved the hallmarks of DSS-colitis. Interestingly, the moderate impact of NAC on lipids and proteins oxidation correlated with myeloperoxidase and nitric oxide levels.NAC as a mucoregulator and a thiol restoring agent is protective on oxidative crypt alterations, mucin depletion, epithelial cell hyperplasia and apoptosis. Taken together, our results highlight the role of NAC as a scavenger of phagocytes-derived reactive oxygen species in mice DDS-colitis, suggesting that a long term NAC diet might be beneficial in inflammatory bowel diseases and colorectal cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

The PI3K/Akt pathway in colitis associated colon cancer and its chemoprevention with celecoxib, a Cox-2 selective inhibitor.

PubMed

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

2014-07-01

Oncogenesis and angiogenesis are the two major pathways involved in tumorigenesis. Oncogenesis involves the PI3K/Akt and Wnt/β-catenin pathways, both of which are upregulated in several types of cancers. We established animal model of ulcerative colitis, colon cancer and colitis associated colon cancer by the incorporation of dextran sufate sodium (DSS) and dimethyl hydrazine (DMH), alone as well as in combination. Apart from the gross morphological analysis, we presently explored the role of various components of the oncogenic pathways, including PI3K, p-Akt, PTEN, PDK1, mTOR, GSK-3β, Wnt and β-catenin and found the elevated levels of these proteins, except the tumor suppressors PTEN and GSK-3β, whose levels were downregulated in both inflammatory and carcinogenic conditions. We also studied the protein expression of some major angiogenic agents, such as Vegf, MMP-2, MMP-9 and iNOS. The angiogenic pathway was also upregulated presently in the DSS, DMH and DSS+DMH groups. Also, the reactive oxygen and nitrogen species, which lead to oxidative stress, were found to be elevated in these groups. All these effects were brought towards normal by the co-administration of celecoxib, a second generation non-steroidal anti-inflammatory drug (NSAID), with DSS, DMH and their combinatorial group. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Rosmarinic acid suppresses colonic inflammation in dextran sulphate sodium (DSS)-induced mice via dual inhibition of NF-κB and STAT3 activation.

PubMed

Jin, Bo-Ram; Chung, Kyung-Sook; Cheon, Se-Yun; Lee, Minho; Hwang, Soonjae; Noh Hwang, Sam; Rhee, Ki-Jong; An, Hyo-Jin

2017-04-06

Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic inflammatory disorder of the colon. Although UC is generally treated with anti-inflammatory drugs or immunosuppressants, most of these treatments often prove to be inadequate. Rosmarinic acid (RA) is a phenolic ester included in various medicinal herbs such as Salvia miltiorrhiz and Perilla frutescens. Although RA has many biological and pharmacological activities, the anti-inflammatory effect of RA in colonic tissue remains unclear. In this study, we investigated the anti-inflammatory effects and underlying molecular mechanism of RA in mice with dextran sulphate sodium (DSS)-induced colitis. In the DSS-induced colitis model, RA significantly reduced the severity of colitis, as assessed by disease activity index (DAI) scores, colonic damage, and colon length. In addition, RA resulted in the reduction of the inflammatory-related cytokines, such as IL-6, IL-1β, and IL-22, and protein levels of COX-2 and iNOS in mice with DSS-induced colitis. Furthermore, RA effectively and pleiotropically inhibited nuclear factor-kappa B and signal transducer and activator of transcription 3 activation, and subsequently reduced the activity of pro-survival genes that depend on these transcription factors. These results demonstrate that RA has an ameliorative effect on colonic inflammation and thus a potential therapeutic role in colitis.

32 CFR 321.8 - DSS review of request for amendment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.8 DSS review of request for... himself and maintained by the Defense Security Service, Office of FOI and Privacy will handle the request... 32 National Defense 2 2012-07-01 2012-07-01 false DSS review of request for amendment. 321.8...

32 CFR 321.8 - DSS review of request for amendment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.8 DSS review of request for... himself and maintained by the Defense Security Service, Office of FOI and Privacy will handle the request... 32 National Defense 2 2010-07-01 2010-07-01 false DSS review of request for amendment. 321.8...

32 CFR 321.8 - DSS review of request for amendment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.8 DSS review of request for... himself and maintained by the Defense Security Service, Office of FOI and Privacy will handle the request... 32 National Defense 2 2011-07-01 2011-07-01 false DSS review of request for amendment. 321.8...

32 CFR 321.8 - DSS review of request for amendment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.8 DSS review of request for... himself and maintained by the Defense Security Service, Office of FOI and Privacy will handle the request... 32 National Defense 2 2013-07-01 2013-07-01 false DSS review of request for amendment. 321.8...

32 CFR 321.8 - DSS review of request for amendment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.8 DSS review of request for... himself and maintained by the Defense Security Service, Office of FOI and Privacy will handle the request... 32 National Defense 2 2014-07-01 2014-07-01 false DSS review of request for amendment. 321.8...

Drill Sergeant Candidate Transformation

DTIC Science & Technology

2009-02-01

leadership styles of NCOs entering Drill Sergeant School (DSS). ARI also developed and administered a prototype DS Assessment Battery to assess...preferred leadership styles . DSS training increases both the degree to which the DSC feels obligated to and identifies with the Army. DSS training...4 TABLE 3. PREFERRED LEADERSHIP STYLES DEFINITIONS .............................................6 TABLE 4. DSC CHANGE IN

The logic of selecting an appropriate map projection in a Decision Support System (DSS)

USGS Publications Warehouse

Finn, Michael P.; Usery, E. Lynn; Woodard, Laura N.; Yamamoto, Kristina H.

2017-01-01

There are undeniable practical consequences to consider when choosing an appropriate map projection for a specific region. The surface of a globe covered by global, continental, and regional maps are so singular that each type distinctively affects the amount of distortion incurred during a projection transformation because of the an assortment of effects caused by distance, direction, scale , and area. A Decision Support System (DSS) for Map Projections of Small Scale Data was previously developed to help select an appropriate projection. This paper reports on a tutorial to accompany that DSS. The DSS poses questions interactively, allowing the user to decide on the parameters, which in turn determines the logic path to a solution. The objective of including a tutorial to accompany the DSS is achieved by visually representing the path of logic that is taken to a recommended map projection derived from the parameters the user selects. The tutorial informs the DSS user about the pedigree of the projection and provides a basic explanation of the specific projection design. This information is provided by informational pop-ups and other aids.

Laboratory investigation of the microbiologically influenced corrosion (MIC) resistance of a novel Cu-bearing 2205 duplex stainless steel in the presence of an aerobic marine Pseudomonas aeruginosa biofilm.

PubMed

Xia, Jin; Yang, Chunguang; Xu, Dake; Sun, Da; Nan, Li; Sun, Ziqing; Li, Qi; Gu, Tingyue; Yang, Ke

2015-01-01

The microbiologically influenced corrosion (MIC) resistance of a novel Cu-bearing 2205 duplex stainless steel (2205 Cu-DSS) against an aerobic marine Pseudomonas aeruginosa biofilm was investigated. The electrochemical test results showed that Rp increased and icorr decreased sharply after long-term immersion in the inoculation medium, suggesting that 2205 Cu-DSS possessed excellent MIC resistance to the P. aeruginosa biofilm. Fluorescence microscope images showed that 2205 Cu-DSS possessed a strong antibacterial ability, and its antibacterial efficiency after one and seven days was 7.75% and 96.92%, respectively. The pit morphology comparison after 14 days between 2205 DSS and 2205 Cu-DSS demonstrated that the latter showed a considerably reduced maximum MIC pit depth compared with the former (1.44 μm vs 9.50 μm). The experimental results suggest that inhibition of the biofilm was caused by the copper ions released from the 2205 Cu-DSS, leading to its effective mitigation of MIC by P. aeruginosa.

Isothiocyanate-enriched moringa seed extract alleviates ulcerative colitis symptoms in mice

PubMed Central

Wu, Alex G.; Jaja-Chimedza, Asha; Graf, Brittany L.; Waterman, Carrie; Verzi, Michael P.; Raskin, Ilya

2017-01-01

Moringa (Moringa oleifera Lam.) seed extract (MSE) has anti-inflammatory and antioxidant activities. We investigated the effects of MSE enriched in moringa isothiocyanate-1 (MIC-1), its putative bioactive, on ulcerative colitis (UC) and its anti-inflammatory/antioxidant mechanism likely mediated through Nrf2-signaling pathway. Dextran sulfate sodium (DSS)-induced acute (n = 8/group; 3% DSS for 5 d) and chronic (n = 6/group; cyclic rotations of 2.5% DSS/water for 30 d) UC was induced in mice that were assigned to 4 experimental groups: healthy control (water/vehicle), disease control (DSS/vehicle), MSE treatment (DSS/MSE), or 5-aminosalicyic acid (5-ASA) treatment (positive control; DSS/5-ASA). Following UC induction, water (vehicle), 150 mg/kg MSE, or 50 mg/kg 5-ASA were orally administered for 1 or 2 wks. Disease activity index (DAI), spleen/colon sizes, and colonic histopathology were measured. From colon and/or fecal samples, pro-inflammatory biomarkers, tight-junction proteins, and Nrf2-mediated enzymes were analyzed at protein and/or gene expression levels. Compared to disease control, MSE decreased DAI scores, and showed an increase in colon lengths and decrease in colon weight/length ratios in both UC models. MSE also reduced colonic inflammation/damage and histopathological scores (modestly) in acute UC. MSE decreased colonic secretions of pro-inflammatory keratinocyte-derived cytokine (KC), tumor necrosis factor (TNF)-α, nitric oxide (NO), and myeloperoxidase (MPO) in acute and chronic UC; reduced fecal lipocalin-2 in acute UC; downregulated gene expression of pro-inflammatory interleukin (IL)-1, IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) in acute UC; upregulated expression of claudin-1 and ZO-1 in acute and chronic UC; and upregulated GSTP1, an Nrf2-mediated phase II detoxifying enzyme, in chronic UC. MSE was effective in mitigating UC symptoms and reducing UC-induced colonic pathologies, likely by suppressing pro-inflammatory biomarkers and increasing tight-junction proteins. This effect is consistent with Nrf2-mediated anti-inflammatory/antioxidant signaling pathway documented for other isothiocyanates similar to MIC-1. Therefore, MSE, enriched with MIC-1, may be useful in prevention and treatment of UC. PMID:28922365

Isothiocyanate-enriched moringa seed extract alleviates ulcerative colitis symptoms in mice.

PubMed

Kim, Youjin; Wu, Alex G; Jaja-Chimedza, Asha; Graf, Brittany L; Waterman, Carrie; Verzi, Michael P; Raskin, Ilya

2017-01-01

Moringa (Moringa oleifera Lam.) seed extract (MSE) has anti-inflammatory and antioxidant activities. We investigated the effects of MSE enriched in moringa isothiocyanate-1 (MIC-1), its putative bioactive, on ulcerative colitis (UC) and its anti-inflammatory/antioxidant mechanism likely mediated through Nrf2-signaling pathway. Dextran sulfate sodium (DSS)-induced acute (n = 8/group; 3% DSS for 5 d) and chronic (n = 6/group; cyclic rotations of 2.5% DSS/water for 30 d) UC was induced in mice that were assigned to 4 experimental groups: healthy control (water/vehicle), disease control (DSS/vehicle), MSE treatment (DSS/MSE), or 5-aminosalicyic acid (5-ASA) treatment (positive control; DSS/5-ASA). Following UC induction, water (vehicle), 150 mg/kg MSE, or 50 mg/kg 5-ASA were orally administered for 1 or 2 wks. Disease activity index (DAI), spleen/colon sizes, and colonic histopathology were measured. From colon and/or fecal samples, pro-inflammatory biomarkers, tight-junction proteins, and Nrf2-mediated enzymes were analyzed at protein and/or gene expression levels. Compared to disease control, MSE decreased DAI scores, and showed an increase in colon lengths and decrease in colon weight/length ratios in both UC models. MSE also reduced colonic inflammation/damage and histopathological scores (modestly) in acute UC. MSE decreased colonic secretions of pro-inflammatory keratinocyte-derived cytokine (KC), tumor necrosis factor (TNF)-α, nitric oxide (NO), and myeloperoxidase (MPO) in acute and chronic UC; reduced fecal lipocalin-2 in acute UC; downregulated gene expression of pro-inflammatory interleukin (IL)-1, IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) in acute UC; upregulated expression of claudin-1 and ZO-1 in acute and chronic UC; and upregulated GSTP1, an Nrf2-mediated phase II detoxifying enzyme, in chronic UC. MSE was effective in mitigating UC symptoms and reducing UC-induced colonic pathologies, likely by suppressing pro-inflammatory biomarkers and increasing tight-junction proteins. This effect is consistent with Nrf2-mediated anti-inflammatory/antioxidant signaling pathway documented for other isothiocyanates similar to MIC-1. Therefore, MSE, enriched with MIC-1, may be useful in prevention and treatment of UC.

Radar RFI at Goldstone DSS 12 and DSS 16

NASA Astrophysics Data System (ADS)

Slobin, S. D.; Peng, T. K.

1990-02-01

Radio frequency interference (RFI) from the DSS 14 Goldstone Solar System Radar (GSSR) was investigated at DSS 12 and DSS 16 with the goal of assisting in the choice of the location of future DSN antennas. Total power measurements at both locations were made at the S-band carrier frequency of 2320 MHz. X-band measurements at the carrier frequency of 8495 MHz could not be made. Exciter-chain output spectrum and klystron output spectrum measurements were made at S- and X-bands using a probable worst-case modulation of the radar signal (short pseudorandom number (PN) code length and short pulse length). Based on these measurements, it is estimated that RFI levels in the DSN receiving bands at both sites (above 10-deg elevation) would be below -192 dBm for a 1-Hz bandwidth

Radar RFI at Goldstone DSS 12 and DSS 16

NASA Technical Reports Server (NTRS)

Slobin, S. D.; Peng, T. K.

1990-01-01

Radio frequency interference (RFI) from the DSS 14 Goldstone Solar System Radar (GSSR) was investigated at DSS 12 and DSS 16 with the goal of assisting in the choice of the location of future DSN antennas. Total power measurements at both locations were made at the S-band carrier frequency of 2320 MHz. X-band measurements at the carrier frequency of 8495 MHz could not be made. Exciter-chain output spectrum and klystron output spectrum measurements were made at S- and X-bands using a probable worst-case modulation of the radar signal (short pseudorandom number (PN) code length and short pulse length). Based on these measurements, it is estimated that RFI levels in the DSN receiving bands at both sites (above 10-deg elevation) would be below -192 dBm for a 1-Hz bandwidth

AQUATOOL, a generalized decision-support system for water-resources planning and operational management

NASA Astrophysics Data System (ADS)

Andreu, J.; Capilla, J.; Sanchís, E.

1996-04-01

This paper describes a generic decision-support system (DSS) which was originally designed for the planning stage of dicision-making associated with complex river basins. Subsequently, it was expanded to incorporate modules relating to the operational stage of decision-making. Computer-assisted design modules allow any complex water-resource system to be represented in graphical form, giving access to geographically referenced databases and knowledge bases. The modelling capability includes basin simulation and optimization modules, an aquifer flow modelling module and two modules for risk assessment. The Segura and Tagus river basins have been used as case studies in the development and validation phases. The value of this DSS is demonstrated by the fact that both River Basin Agencies currently use a version for the efficient management of their water resources.

Intestinal anti-inflammatory activity of apigenin K in two rat colitis models induced by trinitrobenzenesulfonic acid and dextran sulphate sodium.

PubMed

Mascaraque, Cristina; González, Raquel; Suárez, María Dolores; Zarzuelo, Antonio; Sánchez de Medina, Fermín; Martínez-Augustin, Olga

2015-02-28

Flavonoids are polyphenolic compounds that are widespread in nature, and consumed as part of the human diet in significant amounts. The aim of the present study was to test the intestinal anti-inflammatory activity of apigenin K, a soluble form of apigenin, in two models of rat colitis, namely the trinitrobenzenesulfonic acid (TNBS) model and the dextran sulphate sodium (DSS) model. Apigenin K (1, 3 and 10 mg/kg; by the oral route; n 4-6 per group) was administered as a pre-treatment to rats with TNBS and DSS colitis, and colonic status was checked by macroscopic and biochemical examination. Apigenin K pre-treatment resulted in the amelioration of morphological signs and biochemical markers in the TNBS model. The results demonstrated a reduction in the inflamed area, as well as lower values of score and colonic weight:length ratio compared with the TNBS group. Myeloperoxidase (MPO) activity was reduced by 30 % (P< 0·05). Moreover, apigenin K pre-treatment ameliorated morphological signs and biochemical markers in the DSS model. Thus, macroscopic damage was significantly reduced and the colonic weight:length ratio was lowered by approximately 10 %, while colonic MPO and alkaline phosphatase activities were decreased by 35 and 21 %, respectively (P< 0·05). Apigenin K pre-treatment also tended to normalise the expression of a number of colonic inflammatory markers (e.g. TNF-α, transforming growth factor-β, IL-6, intercellular adhesion molecule 1 or chemokine (C-C motif) ligand 2). In conclusion, apigenin K is found to have anti-inflammatory effects in two preclinical models of inflammatory bowel disease.

A mobile decision support system for red eye diseases diagnosis: experience with medical students.

PubMed

López, Marta Manovel; López, Miguel Maldonado; de la Torre Díez, Isabel; Jimeno, José Carlos Pastor; López-Coronado, Miguel

2016-06-01

A good primary health care is the base for a better healthcare system. Taking a good decision on time by the primary health care physician could have a huge repercussion. In order to ease the diagnosis task arise the Decision Support Systems (DSS), which offer counselling instead of refresh the medical knowledge, in a profession where it is still learning every day. The implementation of these systems in diseases which are a frequent cause of visit to the doctor like ophthalmologic pathologies are, which affect directly to our quality of life, takes more importance. This paper aims to develop OphthalDSS, a totally new mobile DSS for red eye diseases diagnosis. The main utilities that OphthalDSS offers will be a study guide for medical students and a clinical decision support system for primary care professionals. Other important goal of this paper is to show the user experience results after OphthalDSS being used by medical students of the University of Valladolid. For achieving the main purpose of this research work, a decision algorithm will be developed and implemented by an Android mobile application. Moreover, the Quality of Experience (QoE) has been evaluated by the students through the questions of a short inquiry. The app developed which implements the algorithm OphthalDSS is capable of diagnose more than 30 eye's anterior segment diseases. A total of 67 medical students have evaluated the QoE. The students find the diseases' information presented very valuable, the appearance is adequate, it is always available and they have ever found what they were looking for. Furthermore, the students think that their quality of life has not been improved using the app and they can do the same without using the OphthalDSS app. OphthalDSS is easy to use, which is capable of diagnose more than 30 ocular diseases in addition to be used as a DSS tool as an educational tool at the same time.

Economic evaluation of DSS 13 unattended operations demonstration

NASA Technical Reports Server (NTRS)

Remer, D. S.; Eisenberger, I.; Lorden, G.

1978-01-01

The goals and data collection requirements to be used for the economic and performance evaluation indexes and life cycle cost parameters for the upcoming operations demonstration of an automated Deep Space Station (DSS) run unattended and controlled remotely from JPL are presented. These evaluation indexes compare the remote operation of telemetry at DSS 13 with the cost and performance of a comparable manned operation at DSS 11. A description is presented of the data that needs to be collected, how the data will be analyzed, and what can and cannot be learned from this operations demonstration.

An Integrated Decision Support System for Water Quality Management of Songhua River Basin

NASA Astrophysics Data System (ADS)

Zhang, Haiping; Yin, Qiuxiao; Chen, Ling

2010-11-01

In the Songhua River Basin of China, many water resource and water environment conflicts interact. A Decision Support System (DSS) for the water quality management has been established for the Basin. The System is featured by the incorporation of a numerical water quality model system into a conventional water quality management system which usually consists of geographic information system (GIS), WebGIS technology, database system and network technology. The model system is built based on DHI MIKE software comprising of a basin rainfall-runoff module, a basin pollution load evaluation module, a river hydrodynamic module and a river water quality module. The DSS provides a friendly graphical user interface that enables the rapid and transparent calculation of various water quality management scenarios, and also enables the convenient access and interpretation of the modeling results to assist the decision-making.

Comparative Evaluation between Sulfasalazine Alone and in Combination with Herbal Medicine on DSS-Induced Ulcerative Colitis Mice

PubMed Central

Shin, Mi-Rae; Kim, Kyeong Jo; Kim, Soo Hyun; Kim, Su Ji

2017-01-01

The present study aimed to investigate the comparative evaluation of pharmacological efficacy between sulfasalazine alone and sulfasalazine in combination with herbal medicine on dextran sodium sulfate- (DSS-) induced UC in mice. Balb/c mice received 5% DSS in drinking water for 7 days to induce colitis. Animals were divided into five groups (n = 9): Group I (normal group), Group II (DSS control group), Group III (DSS + sulfasalazine (30 mg/kg)), Group IV (DSS + sulfasalazine (60 mg/kg)), and Group V (DSS + sulfasalazine (30 mg/kg) + Cinnamomi Cortex and Bupleuri Radix mixture (30 mg/kg) (SCB)). Colonic pathological changes were analyzed using hematoxyline/eosin staining. The antioxidant, inflammatory, and apoptotic protein levels were determined using western blotting. SCB supplementation, as well as sulfasalazine, suppressed colonic length and mucosal inflammatory infiltration. In addition, SCB treatment significantly reduced the expression of proinflammatory signaling molecules through suppression of both mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways and prevented the apoptosis of the colon. Moreover, SCB administration significantly led to the upregulation of antioxidant enzymes including SOD and catalase. Taken together, SCB treatment might offer a better treatment for human UC than sulfasalazine alone or may be useful as an alternative therapeutic strategy against UC, without any evidence of side effects. PMID:29018816

Hardfacing of duplex stainless steel using melting and diffusion processes

NASA Astrophysics Data System (ADS)

Lailatul, H.; Maleque, M. A.

2017-03-01

Duplex stainless steel (DSS) is a material with high potential successes in many new applications such as rail car manufacturing, automotive and chemical industries. Although DSS is widely used in various industries, this material has faced wear and hardness problems which obstruct a wider capability of this material and causes problems in current application. Therefore, development of surface modification has been introduced to produce hard protective layer or coating on DSS. The main aim of this work is to brief review on hard surface layer formation on DSS using melting and diffusion processes. Melting technique using tungsten inert gas (TIG) torch and diffusion technique using gas nitriding are the effective process to meet this requirement. The processing route plays a significant role in developing the hard surface layer for any application with effective cost and environmental factors. The good understanding and careful selection of processing route to form products are very important factors to decide the suitable techniques for surface engineering treatment. In this paper, an attempt is also made to consolidate the important research works done on melting and diffusion techniques of DSS in the past. The advantages and disadvantages between melting and diffusion technique are presented for better understanding on the feasibility of hard surface formation on DSS. Finally, it can be concluded that this work will open an avenue for further research on the application of suitable process for hard surface formation on DSS.

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

Xilei san ameliorates experimental colitis in rats by selectively degrading proinflammatory mediators and promoting mucosal repair.

PubMed

Hao, Yongbiao; Nagase, Kazuko; Hori, Kazutoshi; Wang, Shenglan; Kogure, Yoko; Fukunaga, Ken; Kashiwamura, Shinichiro; Yamamoto, Satoshi; Nakamura, Shiro; Li, Junxiang; Miwa, Hiroto; Noguchi, Koichi; Dai, Yi

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.

In vivo biocompatibility of a new cyanine dye for ILM peeling

PubMed Central

Thaler, S; Haritoglou, C; Schuettauf, F; Choragiewicz, T; May, C A; Gekeler, F; Fischer, M D; Langhals, H; Schatz, A

2015-01-01

Purpose To investigate the biocompatibility of the new cyanine dye: 3,3′-Di-(4-sulfobutyl)-1,1,1′,1′-tetramethyl-di-1H-benz[e]indocarbocyanine (DSS) as a vital dye for intraocular application in an in vivo rat model and to evaluate the effects of this dye on retinal structure and function. Methods DSS at a concentration of 0.5% was applied via intravitreal injections to adult Brown Norway rats with BSS serving as a control. Retinal toxicity was assessed 7 days later by means of retinal ganglion cell (RGC) counts, light microscopy, optical coherence tomography (OCT), and electroretinography (ERG). Results No significant decrease in RGC numbers was observed. No structural changes of the central retina were observed either in vivo (OCT) or under light microscopy. ERGs detected a temporary reduction of retinal function 7 days after injection; this was no longer evident 14 days after injection. Conclusions DSS showed good biocompatibility in a well-established experimental in vivo setting and may be usable for intraocular surgery as an alternative to other cyanine dyes. In contrast to indocyanine green, it additionally offers fluorescence in the visual spectrum. Further studies with other animal models are needed before translation into clinical application. PMID:25523205

6-Gingerol modulates proinflammatory responses in dextran sodium sulfate (DSS)-treated Caco-2 cells and experimental colitis in mice through adenosine monophosphate-activated protein kinase (AMPK) activation.

PubMed

Chang, Kuei-Wen; Kuo, Cheng-Yi

2015-10-01

6-gingerol has been reported to have anti-inflammatory effects in different experimental settings. The present study aimed at evaluating the effect of 6-gingerol on dextran sodium sulfate (DSS)-induced barrier impairment and inflammation in vitro and in vivo. a differentiated Caco-2 monolayer was exposed to DSS and treated with different concentrations of 6-gingerol (0, 1, 5, 10, 50, and 100 μM). Changes in intestinal barrier function were determined using transepithelial electrical resistance (TEER). The anti-inflammatory activity of 6-gingerol was examined as changes in the expression of proinflammatory cytokine using quantitative real-time PCR. Western blotting was employed to determine the activation of adenosine monophosphate-activated protein kinase (AMPK). Mice with DSS-induced colitis were given different oral dosages of 6-gingerol daily for 14 days. Body weight and colon inflammation were evaluated, and level of proinflammatory cytokines in colon tissues was measured. 6-gingerol treatment was shown to restore impaired intestinal barrier function and to suppress proinflammatory responses in DSS-treated Caco-2 monolayers. We found that AMPK was activated on 6-gingerol treatment in vitro. In animal studies, 6-gingerol significantly ameliorated DSS-induced colitis by restoration of body weight loss, reduction in intestinal bleeding, and prevention of colon length shortening. In addition, 6-gingerol suppressed DSS-elevated production of proinflammatory cytokines (IL-1β, TNFα, and IL-12). our findings highlight the protective effects of 6-gingerol against DSS-induced colitis. We concluded that 6-gingerol exerts anti-inflammatory effects through AMPK activation. It is suggested that 6-gingerol has a promising role in treatment of IBD.

Evaluation of computerized decision support for oral anticoagulation management based in primary care.

PubMed

Fitzmaurice, D A; Hobbs, F D; Murray, E T; Bradley, C P; Holder, R

1996-09-01

Increasing indications for oral anticoagulation has led to pressure on general practices to undertake therapeutic monitoring. Computerized decision support (DSS) has been shown to be effective in hospitals for improving clinical management. Its usefulness in primary care has previously not been investigated. To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled, defined as within the appropriate therapeutic range of International Normalised Ratio (INR). All patients receiving warfarin from two Birmingham inner city general practices were invited to attend a practice-based anticoagulation clinic. In practice A all patients were managed using DSS. In practice B patients were randomized to receive dosing advice either through DSS or through the local hospital laboratory. Clinical outcomes, adverse events and patient acceptability were recorded. Forty-nine patients were seen in total. There were significant improvements in INR control from 23% to 86% (P > 0.001) in the practice where all patients received dosing through DSS. In the practice where patients were randomized to either DSS or hospital dosing, logistic regression showed a significant trend for improvement in intervention patients which was not apparent in the hospital-dosed patients (P < 0.001). Mean recall times were significantly extended in patients who were dosed by the practice DSS through the full 12 months (24 days to 36 days) (P = 0.033). Adverse events were comparable between hospital and practice-dosed patients, although a number of esoteric events occurred. Patient satisfaction with the practice clinics was high. Computerized DSS enables the safe and effective transfer of anticoagulation management from hospital to primary care and may result in improved patient outcome in terms of the level of control, frequency of review and general acceptability.

High fat diet exacerbates dextran sulfate sodium induced colitis through disturbing mucosal dendritic cell homeostasis.

PubMed

Cheng, Lu; Jin, Huimin; Qiang, Yetao; Wu, Shuiyun; Yan, Cheng; Han, Mutian; Xiao, Tengfei; Yan, Nannan; An, Huazhang; Zhou, Xiaoming; Shao, Qixiang; Xia, Sheng

2016-11-01

Epidemiological studies have shown that fat rich western diet contributes to the high incidence of inflammatory bowel disease (IBD). Moreover, accumulated data indicated that fat dietary factor might promote the change of the composition and metabolism in commensal flora. But, the exact mechanisms for fatty diet in gut inflammation are not well demonstrated. In this study, we found that high fat diet (HFD) promoted inflammation and exacerbated the disease severity of dextran sulfate sodium (DSS) induced colitis in mice. Compared with low fat diet (LFD)/DSS mice, shorter colon length, more epithelial loss and crypt destruction and more Gr-1 + myeloid inflammatory cells infiltration in colons were observed in HFD/DSS cohorts. Interestingly, such HFD mediated inflammation accompanied with the dys-regulation of hematopoiesis, and more hematopoiesis stem and progenitor cells were detected in colon and spleen. We further analyzed the effects of HFD and DSS treatment on mucosal DC subsets, and found that DSS treatment in LFD mice mainly dramatically increased the percentage of CD11c + CD103 - CD11b + DCs in lamina propria (LP). While, in HFD/DSS mice, HFD pre-treatment not only increased the percentage of CD11c + CD103 - CD11b + DCs, but also decreased CD11c + CD103 + CD11b + in both LP and mesenteric lymph nodes (MLN) in mice with colitis. This disequilibrium of mucosal dendritic cells in HFD/DSS mice may depend on the reduced levels of buytrate and retinoic acid. Thus, this study declared the effects of HFD on gut microenviroment, and further indicated its potential role in the development of DSS induced colitis. Copyright © 2016 Elsevier B.V. All rights reserved.

Geographic region: Does it matter in cutaneous melanoma of the head and neck?

PubMed

Kılıç, Suat; Unsal, Aykut A; Chung, Sei Y; Samarrai, Ruwaa; Kılıç, Sarah S; Baredes, Soly; Eloy, Jean Anderson

2017-12-01

The head and neck are two of the most common locations for cutaneous melanoma. We present the first population-based analysis of geographic differences in anatomic subsite, clinicopathologic and demographical traits, histopathologic subtype, treatment modality, and disease-specific survival (DSS) of cutaneous head and neck melanoma (CHNM). Retrospective database analysis. The Surveillance, Epidemiology, and End Results database was queried for cases of CHNM reported between 2000 and 2013. Patients were grouped into East, Midwest, South, and West regions of the United States. Overall incidence, demographic traits, primary tumor site, clinicopathologic traits, histopathologic subtype, treatment modality, and DSS were compared among regions. There were 49,365 patients with CHNM identified. The West (4.60) and the South (4.42) had significantly higher incidence (per 100,000) than the East (3.84) and Midwest (3.65) (P < .05). DSS was significantly different among regions (P < .0066). The East (5 years: 89.4%, 10 years: 84.1%) had the highest DSS rate, and the South (5 years: 87.0%, 10 years: 81.8%) had the lowest DSS rate. The Midwest (5 years: 88.4%, 10 years: 84.3%) and West (5 years: 88.3%, 10 years: 83.5%) had intermediate DSS. On multivariate analysis, the South had an elevated hazard ratio (1.17, 95% confidence interval: 1.05-1.30) when compared to the West. Geographic region may play a significant role in CHNM. Incidence is higher in the South and the West. Incidence, histologic subtype, treatment modality, and DSS vary among regions. DSS is lower in the South than the West, even after accounting for other major prognostic factors. 4. Laryngoscope, 127:2763-2769, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

NASA ground terminal communication equipment automated fault isolation expert systems

NASA Technical Reports Server (NTRS)

Tang, Y. K.; Wetzel, C. R.

1990-01-01

The prototype expert systems are described that diagnose the Distribution and Switching System I and II (DSS1 and DSS2), Statistical Multiplexers (SM), and Multiplexer and Demultiplexer systems (MDM) at the NASA Ground Terminal (NGT). A system level fault isolation expert system monitors the activities of a selected data stream, verifies that the fault exists in the NGT and identifies the faulty equipment. Equipment level fault isolation expert systems are invoked to isolate the fault to a Line Replaceable Unit (LRU) level. Input and sometimes output data stream activities for the equipment are available. The system level fault isolation expert system compares the equipment input and output status for a data stream and performs loopback tests (if necessary) to isolate the faulty equipment. The equipment level fault isolation system utilizes the process of elimination and/or the maintenance personnel's fault isolation experience stored in its knowledge base. The DSS1, DSS2 and SM fault isolation systems, using the knowledge of the current equipment configuration and the equipment circuitry issues a set of test connections according to the predefined rules. The faulty component or board can be identified by the expert system by analyzing the test results. The MDM fault isolation system correlates the failure symptoms with the faulty component based on maintenance personnel experience. The faulty component can be determined by knowing the failure symptoms. The DSS1, DSS2, SM, and MDM equipment simulators are implemented in PASCAL. The DSS1 fault isolation expert system was converted to C language from VP-Expert and integrated into the NGT automation software for offline switch diagnoses. Potentially, the NGT fault isolation algorithms can be used for the DSS1, SM, amd MDM located at Goddard Space Flight Center (GSFC).

Evaluation of Effectiveness and Cost‐Effectiveness of a Clinical Decision Support System in Managing Hypertension in Resource Constrained Primary Health Care Settings: Results From a Cluster Randomized Trial

PubMed Central

Anchala, Raghupathy; Kaptoge, Stephen; Pant, Hira; Di Angelantonio, Emanuele; Franco, Oscar H.; Prabhakaran, D.

2015-01-01

Background Randomized control trials from the developed world report that clinical decision support systems (DSS) could provide an effective means to improve the management of hypertension (HTN). However, evidence from developing countries in this regard is rather limited, and there is a need to assess the impact of a clinical DSS on managing HTN in primary health care center (PHC) settings. Methods and Results We performed a cluster randomized trial to test the effectiveness and cost‐effectiveness of a clinical DSS among Indian adult hypertensive patients (between 35 and 64 years of age), wherein 16 PHC clusters from a district of Telangana state, India, were randomized to receive either a DSS or a chart‐based support (CBS) system. Each intervention arm had 8 PHC clusters, with a mean of 102 hypertensive patients per cluster (n=845 in DSS and 783 in CBS groups). Mean change in systolic blood pressure (SBP) from baseline to 12 months was the primary endpoint. The mean difference in SBP change from baseline between the DSS and CBS at the 12th month of follow‐up, adjusted for age, sex, height, waist, body mass index, alcohol consumption, vegetable intake, pickle intake, and baseline differences in blood pressure, was −6.59 mm Hg (95% confidence interval: −12.18 to −1.42; P=0.021). The cost‐effective ratio for CBS and DSS groups was $96.01 and $36.57 per mm of SBP reduction, respectively. Conclusion Clinical DSS are effective and cost‐effective in the management of HTN in resource‐constrained PHC settings. Clinical Trial Registration URL: http://www.ctri.nic.in. Unique identifier: CTRI/2012/03/002476. PMID:25559011

A Decision Support System for Evaluating and Selecting Information Systems Projects

NASA Astrophysics Data System (ADS)

Deng, Hepu; Wibowo, Santoso

2009-01-01

This chapter presents a decision support system (DSS) for effectively solving the information systems (IS) project selection problem. The proposed DSS recognizes the multidimensional nature of the IS project selection problem, the availability of multicriteria analysis (MA) methods, and the preferences of the decision-maker (DM) on the use of specific MA methods in a given situation. A knowledge base consisting of IF-THEN production rules is developed for assisting the DM with a systematic adoption of the most appropriate method with the efficient use of the powerful reasoning and explanation capabilities of intelligent DSS. The idea of letting the problem to be solved determines the method to be used is incorporated into the proposed DSS. As a result, effective decisions can be made for solving the IS project selection problem. An example is presented to demonstrate the applicability of the proposed DSS for solving the problem of selecting IS projects in real world situations.

An overview of emerging technologies in contemporary decision support system development

NASA Astrophysics Data System (ADS)

Nursal, Ahmad Taufik; Omar, Mohd Faizal; Nawi, Mohd Nasrun Mohd

2014-12-01

The rapid development of Web technology has opened a new approach to Decision Support System (DSS) development. For instance, Social Media is one of the Web 2.0 digital platforms that allow the creation and exchanges of user-generate content through an interactive interface, high user control and mass participation. The concept and characteristics of Web 2.0 such as remote, platform-independent, context-rich and easy to use, which is fulfill the concept and purpose of DSS. This paper outlines some of the elementary concepts of Web 2.0 and social media technology which can be potentially integrated within DSS to enhance the decision-making process. Our initial investigation indicates that there is limited study attempt to embed Web 2.0 into DSS. Thus, this paper highlights the importance of Web 2.0 technology in order to foster the betterment of DSS development and its usability.

Natural Poly- and Oligosaccharides as Novel Delivery Systems for Plant Protection Compounds.

PubMed

Selyutina, O Yu; Apanasenko, I E; Khalikov, S S; Polyakov, N E

2017-08-09

To increase the bioavailability of plant protection products, we have applied a new approach based on noncovalent association with natural water-soluble polysaccharides and oligosaccharides as delivery systems (DSs). The mechanochemical technique has been applied to prepare the solid-state nanodispersed compositions of antidote 1,8-naphthalic anhydride (NA) with arabinogalactan, sodium salt of carboxymethylcellulose, and glycyrrhizin as DSs. The effect of DSs on the solubility and the penetration of NA into the seeds of barley and wheat has been investigated by various physicochemical techniques. All DSs considerably enhance the solubility of NA and improve its penetration into the grain. The influence of polysaccharides and oligosaccharides on artificial lipid membranes was studied by the NMR relaxation method. It was concluded that the effect of polysaccharides and oligosaccharides on the penetration efficacy of plant protection products might be associated with the detected solubility enhancement and the affinity of DSs to the surface of cell membranes.

Glutathione peroxidase-2 and selenium decreased inflammation and tumors in a mouse model of inflammation-associated carcinogenesis whereas sulforaphane effects differed with selenium supply

PubMed Central

Krehl, Susanne; Loewinger, Maria; Florian, Simone; Kipp, Anna P.; Banning, Antje; Wessjohann, Ludger A.; Brauer, Martin N.; Iori, Renato; Esworthy, Robert S.; Chu, Fong-Fong; Brigelius-Flohé, Regina

2012-01-01

Chronic inflammation and selenium deficiency are considered as risk factors for colon cancer. The protective effect of selenium might be mediated by specific selenoproteins, such as glutathione peroxidases (GPx). GPx-1 and -2 double knockout, but not single knockout mice, spontaneously develop ileocolitis and intestinal cancer. Since GPx2 is induced by the chemopreventive sulforaphane (SFN) via the nuclear factor E2-related factor 2 (Nrf2)/Keap1 system, the susceptibility of GPx2-KO and wild-type (WT) mice to azoxymethane and dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis was tested under different selenium states and SFN applications. WT and GPx2-KO mice were grown on a selenium-poor, -adequate or -supranutritional diet. SFN application started either 1 week before (SFN4) or along with (SFN3) a single AOM application followed by DSS treatment for 1 week. Mice were assessed 3 weeks after AOM for colitis and Nrf2 target gene expression and after 12 weeks for tumorigenesis. NAD(P)H:quinone oxidoreductases, thioredoxin reductases and glutathione-S-transferases were upregulated in the ileum and/or colon by SFN, as was GPx2 in WT mice. Inflammation scores were more severe in GPx2-KO mice and highest in selenium-poor groups. Inflammation was enhanced by SFN4 in both genotypes under selenium restriction but decreased in selenium adequacy. Total tumor numbers were higher in GPx2-KO mice but diminished by increasing selenium in both genotypes. SFN3 reduced inflammation and tumor multiplicity in both Se-adequate genotypes. Tumor size was smaller in Se-poor GPx2-KO mice. It is concluded that GPx2, although supporting tumor growth, inhibits inflammation-mediated tumorigenesis, but the protective effect of selenium does not strictly depend on GPx2 expression. Similarly, SFN requires selenium but not GPx2 for being protective. PMID:22180572

Glutathione peroxidase-2 and selenium decreased inflammation and tumors in a mouse model of inflammation-associated carcinogenesis whereas sulforaphane effects differed with selenium supply.

PubMed

Krehl, Susanne; Loewinger, Maria; Florian, Simone; Kipp, Anna P; Banning, Antje; Wessjohann, Ludger A; Brauer, Martin N; Iori, Renato; Esworthy, Robert S; Chu, Fong-Fong; Brigelius-Flohé, Regina

2012-03-01

Chronic inflammation and selenium deficiency are considered as risk factors for colon cancer. The protective effect of selenium might be mediated by specific selenoproteins, such as glutathione peroxidases (GPx). GPx-1 and -2 double knockout, but not single knockout mice, spontaneously develop ileocolitis and intestinal cancer. Since GPx2 is induced by the chemopreventive sulforaphane (SFN) via the nuclear factor E2-related factor 2 (Nrf2)/Keap1 system, the susceptibility of GPx2-KO and wild-type (WT) mice to azoxymethane and dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis was tested under different selenium states and SFN applications. WT and GPx2-KO mice were grown on a selenium-poor, -adequate or -supranutritional diet. SFN application started either 1 week before (SFN4) or along with (SFN3) a single AOM application followed by DSS treatment for 1 week. Mice were assessed 3 weeks after AOM for colitis and Nrf2 target gene expression and after 12 weeks for tumorigenesis. NAD(P)H:quinone oxidoreductases, thioredoxin reductases and glutathione-S-transferases were upregulated in the ileum and/or colon by SFN, as was GPx2 in WT mice. Inflammation scores were more severe in GPx2-KO mice and highest in selenium-poor groups. Inflammation was enhanced by SFN4 in both genotypes under selenium restriction but decreased in selenium adequacy. Total tumor numbers were higher in GPx2-KO mice but diminished by increasing selenium in both genotypes. SFN3 reduced inflammation and tumor multiplicity in both Se-adequate genotypes. Tumor size was smaller in Se-poor GPx2-KO mice. It is concluded that GPx2, although supporting tumor growth, inhibits inflammation-mediated tumorigenesis, but the protective effect of selenium does not strictly depend on GPx2 expression. Similarly, SFN requires selenium but not GPx2 for being protective.

Extracellular Vesicles From the Helminth Fasciola hepatica Prevent DSS-Induced Acute Ulcerative Colitis in a T-Lymphocyte Independent Mode

PubMed Central

Roig, Javier; Saiz, Maria L.; Galiano, Alicia; Trelis, Maria; Cantalapiedra, Fernando; Monteagudo, Carlos; Giner, Elisa; Giner, Rosa M.; Recio, M. C.; Bernal, Dolores; Sánchez-Madrid, Francisco; Marcilla, Antonio

2018-01-01

The complexity of the pathogenesis of inflammatory bowel disease (ulcerative colitis and Crohn’s disease) has led to the quest of empirically drug therapies, combining immunosuppressant agents, biological therapy and modulators of the microbiota. Helminth parasites have been proposed as an alternative treatment of these diseases based on the hygiene hypothesis, but ethical and medical problems arise. Recent reports have proved the utility of parasite materials, mainly excretory/secretory products as therapeutic agents. The identification of extracellular vesicles on those secreted products opens a new field of investigation, since they exert potent immunomodulating effects. To assess the effect of extracellular vesicles produced by helminth parasites to treat ulcerative colitis, we have analyzed whether extracellular vesicles produced by the parasitic helminth Fasciola hepatica can prevent colitis induced by chemical agents in a mouse model. Adult parasites were cultured in vitro and secreted extracellular vesicles were purified and used for immunizing both wild type C57BL/6 and RAG1-/- mice. Control and immunized mice groups were treated with dextran sulfate sodium 7 days after last immunization to promote experimental colitis. The severity of colitis was assessed by disease activity index and histopathological scores. Mucosal cytokine expression was evaluated by ELISA. The activation of NF-kB, COX-2, and MAPK were evaluated by immunoblotting. Administration of extracellular vesicles from F. hepatica ameliorates the pathological symptoms reducing the amount of pro-inflammatory cytokines and interfering with both MAPK and NF-kB pathways. Interestingly, the observed effects do not seem to be mediated by T-cells. Our results indicate that extracellular vesicles from parasitic helminths can modulate immune responses in dextran sulfate sodium (DSS)-induced colitis, exerting a protective effect that should be mediated by other cells distinct from B- and T-lymphocytes. PMID:29875750

Environmental projects, volume 10. Environmental assessment: New 34-meter antenna at Apollo site

NASA Technical Reports Server (NTRS)

1990-01-01

The Goldstone Deep Space Communications Complex (GDSCC) is part of NASA's Deep Space Network (DSN), one of the world's largest and most sensitive scientific telecommunications and radio navigation networks. A detailed description of the GDSCC is presented. At present the Venus Station has an unused 9-meter antenna and a 26-meter (85 ft) antenna known as DSS-13. Construction of a new 34-meter (111.5 ft) antenna at the Venus site is under way to replace the present DSS-13 26-meter antenna. The proposed construction at the Apollo Site of a new, high efficiency, 34-meter, multifrequency beam waveguide-type antenna to replace the aging, 20-year old, DSS-12 34-meter antenna located at the Echo Site is analyzed. This new 34-meter antenna, to be constructed at the Apollo Site and to be known as DSS-18, will be of a design similar to the new DSS-13 34-meter antenna now being constructed at the Venus Site. When the new 34-meter antenna is completed and operational at the Apollo Site (planned for 1993), the old DSS-12 34-meter antenna at the Echo Site will be decommissioned, dismantled, and removed.

Cyclic stress effect on stress corrosion cracking of duplex stainless steel in chloride and caustic solutions

NASA Astrophysics Data System (ADS)

Yang, Di

Duplex stainless steel (DSS) is a dual-phase material with approximately equal volume amount of austenite and ferrite. It has both great mechanical properties (good ductility and high tensile/fatigue strength) and excellent corrosion resistance due to the mixture of the two phases. Cyclic loadings with high stress level and low frequency are experienced by many structures. However, the existing study on corrosion fatigue (CF) study of various metallic materials has mainly concentrated on relatively high frequency range. No systematic study has been done to understand the ultra-low frequency (˜10-5 Hz) cyclic loading effect on stress corrosion cracking (SCC) of DSSs. In this study, the ultra-low frequency cyclic loading effect on SCC of DSS 2205 was studied in acidified sodium chloride and caustic white liquor (WL) solutions. The research work focused on the environmental effect on SCC of DSS 2205, the cyclic stress effect on strain accumulation behavior of DSS 2205, and the combined environmental and cyclic stress effect on the stress corrosion crack initiation of DSS 2205 in the above environments. Potentiodynamic polarization tests were performed to investigate the electrochemical behavior of DSS 2205 in acidic NaCl solution. Series of slow strain rate tests (SSRTs) at different applied potential values were conducted to reveal the optimum applied potential value for SCC to happen. Room temperature static and cyclic creep tests were performed in air to illustrate the strain accumulation effect of cyclic stresses. Test results showed that cyclic loading could enhance strain accumulation in DSS 2205 compared to static loading. Moreover, the strain accumulation behavior of DSS 2205 was found to be controlled by the two phases of DSS 2205 with different crystal structures. The B.C.C. ferrite phase enhanced strain accumulation due to extensive cross-slips of the dislocations, whereas the F.C.C. austenite phase resisted strain accumulation due to cyclic strain hardening. Cyclic SSRTs were performed under the conditions that SCC occurs in sodium chloride and WL solutions. Test results show that cyclic stress facilitated crack initiations in DSS 2205. Stress corrosion cracks initiated from the intermetallic precipitates in acidic chloride environment, and the cracks initiated from austenite phase in WL environment. Cold-working has been found to retard the crack initiations induced by cyclic stresses.

Local and systemic immune mechanisms underlying the anti-colitis effects of the dairy bacterium Lactobacillus delbrueckii.

PubMed

Santos Rocha, Clarissa; Gomes-Santos, Ana Cristina; Garcias Moreira, Thais; de Azevedo, Marcela; Diniz Luerce, Tessalia; Mariadassou, Mahendra; Longaray Delamare, Ana Paula; Langella, Philippe; Maguin, Emmanuelle; Azevedo, Vasco; Caetano de Faria, Ana Maria; Miyoshi, Anderson; van de Guchte, Maarten

2014-01-01

Several probiotic bacteria have been proposed for treatment or prevention of inflammatory bowel diseases (IBD), showing a protective effect in animal models of experimental colitis and for some of them also in human clinical trials. While most of these probiotic bacteria are isolated from the digestive tract, we recently reported that a Lactobacillus strain isolated from cheese, L. delbrueckii subsp. lactis CNRZ327 (Lb CNRZ327), also possesses anti-inflammatory effects in vitro and in vivo, demonstrating that common dairy bacteria may be useful in the treatment or prevention of IBD. Here, we studied the mechanisms underlying the protective effects of Lb CNRZ327 in vivo, in a mouse dextran sodium sulfate (DSS) colitis model. During colitis, Lb CNRZ327 modulated the production of TGF-β, IL-6, and IL-12 in colonic tissue and of TGF-β and IL-6 in the spleen, and caused an expansion of CD4+Foxp3+ regulatory T cells in the cecal lymph nodes. Moreover, a strong tendency to CD4+Foxp3+ expansion was also observed in the spleen. The results of this study for the first time show that orally administered dairy lactobacilli can not only modulate mucosal but also systemic immune responses and constitute an effective treatment of IBD.

Validation of a gastric cancer nomogram using a cancer registry.

PubMed

Ashfaq, Awais; Kidwell, John T; McGhan, Lee J; Dueck, Amylou C; Pockaj, Barbara A; Gray, Richard J; Bagaria, Sanjay P; Wasif, Nabil

2015-09-01

A Memorial Sloan Kettering (MSKCC) nomogram predicts disease specific survival (DSS) for gastric adenocarcinoma. The goal of this study is to use a cancer registry to compare nomogram predicted survival with actual survival in the general population. All patients undergoing surgery for gastric adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database (1988-2012) were studied. 6954 patients were identified. Majority of cancers were in the antrum (30.2%), and had intestinal histology (73.7%). Median follow-up was 8.2 years. Five year DSS for nomogram risk groups (0-25%, 26-50%, 51-75%, and 76-100%) was 23%, 48%, 57%, and 81% respectively. Actual DSS was 7-15% lower than nomogram predicted DSS. Relative to patients in the 76-100% 5-year DSS risk group, patients in the 0-25%, 26-50%, and 51-75% groups had significantly higher risks of death with hazard ratios of 6.84 (95%CI 6.12-7.65), 3.30 (95%CI 2.83-3.86), and 2.64 (95%CI 2.30-3.03), respectively (all P < 0.001). The concordance index for 5-year nomogram predicted DSS was 0.68 (95%CI 0.67-0.69). The MSKCC gastric cancer nomogram over-estimates DSS from gastric cancer in the general population and has a moderate concordance index. Predictive tools generated at specialized institutions may not perform as well in the general population. © 2015 Wiley Periodicals, Inc.

Changes of the peptide YY levels in the intestinal tissue of rats with experimental colitis following oral administration of mesalazine and prednisolone.

PubMed

Hirotani, Yoshihiko; Mikajiri, Kyoko; Ikeda, Kenji; Myotoku, Michiaki; Kurokawa, Nobuo

2008-09-01

Few studies have reported the changes in the peptide YY (PYY) levels in the intestinal tissue of rats with ulcerative colitis (UC) following oral administration of mesalazine and prednisolone. We investigated the effects of these drugs on the intestinal mucosal PYY levels in a rat model of UC. We confirmed that the PYY levels in the rat intestinal mucosal tissue were high in the lower intestinal tract. The leukocyte count and hemoglobin levels approached the normal values after administering mesalazine or prednisolone to rats treated with 3% dextran sulfate sodium (DSS). The PYY levels in the caecum and colon decreased significantly after administering DSS but increased when mesalazine was administered in a tissue-specific manner. Unlike mesalazine, the PYY levels increased in the ileum in addition to the colon and rectum after administering prednisolone. However, neither of the drugs induced any changes in the plasma PYY levels. These findings indicate that changes in the intestinal tissue PYY levels may be partially involved in the improvement of DSS-induced UC in rats following the administration of these drugs.

A Decision Support System For The Real-Time Allocation Of The Water Resource Of The Tarim River Basin, China

NASA Astrophysics Data System (ADS)

Wei, J.; Wang, G.; Liu, R.

2008-12-01

The Tarim River Basin is the longest inland river in China. Due to water scarcity, ecologically-fragile is becoming a significant constraint to sustainable development in this region. To effectively manage the limited water resources for ecological purposes and for conventional water utilization purposes, a real-time water resources allocation Decision Support System (DSS) has been developed. Based on workflows of the water resources regulations and comprehensive analysis of the efficiency and feasibility of water management strategies, the DSS includes information systems that perform data acquisition, management and visualization, and model systems that perform hydrological forecast, water demand prediction, flow routing simulation and water resources optimization of the hydrological and water utilization process. An optimization and process control strategy is employed to dynamically allocate the water resources among the different stakeholders. The competitive targets and constraints are taken into considered by multi-objective optimization and with different priorities. The DSS of the Tarim River Basin has been developed and been successfully utilized to support the water resources management of the Tarim River Basin since 2005.

Cytokine production in vitro and in rat model of colitis in response to Lactobacillus plantarum LS/07.

PubMed

Štofilová, Jana; Langerholc, Tomaž; Botta, Cristian; Treven, Primož; Gradišnik, Lidija; Salaj, Rastislav; Šoltésová, Alena; Bertková, Izabela; Hertelyová, Zdenka; Bomba, Alojz

2017-10-01

Over the past decade, it has become clear that specific probiotic lactobacilli are valuable in the prevention and treatment of infectious and inflammatory diseases of gastrointestinal tract but their successful application would benefit greatly from a better understanding of the mechanisms of individual strains. Hence, each probiotic strain should be characterized for their immune activity before being proposed for clinical applications. The aim of the study was to characterize the immunomodulatory activity of the strain Lactobacillus (L.) plantarum LS/07 in vitro using functional gut model and to study its anti-inflammatory potential in dextran sulphate sodium (DSS)-induced colitis in rats. We showed that L. plantarum LS/07 induced production of IL-10 in macrophages derived from blood monocytes as well as monocyte/macrophages cell line stimulated indirectly via enterocytes in vitro. In rat model of colitis, L. plantarum LS/07 attenuated the DSS-induced signs of inflammatory process in colon such as weight loss, diarrhoea, infiltration of inflammatory cells associated with decreased colon weight/length ratio, inhibited gut mucosa destruction and depletion of goblet cells. Moreover, the strain increased the concentration of anti-inflammatory cytokine IL-10 in mucosal tissue. In conclusion, the protective effects of L. plantarum LS/07 in the DSS-induced colitis model seem to be related to the stimulation of IL-10 and the restoration of goblet cells and indicate it as a good candidate to prevent and treat diseases associated with inflammation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Physicochemical and nutraceutical properties of moringa (Moringa oleifera) leaves and their effects in an in vivo AOM/DSS-induced colorectal carcinogenesis model.

PubMed

Cuellar-Nuñez, M L; Luzardo-Ocampo, I; Campos-Vega, R; Gallegos-Corona, M A; González de Mejía, E; Loarca-Piña, G

2018-03-01

Moringa (Moringa oleifera) is a plant that has generated great interest in recent years because of its attributed medicinal properties. The aim of this study was to characterize the bioactive compounds of moringa leaves (MO) and evaluate their effect on a colorectal carcinogenesis model. Twenty-four male CD-1 mice were divided into 4 groups: Group 1 fed with basal diet (negative control/NC); Group 2 received AOM/DSS (positive control); Groups 3 and 4 were fed with basal diet supplemented with moringa leaves (2.5% w/w and 5% w/w, respectively) for 12weeks. Moringa leaves exhibited a high content of dietary fiber (~18.75%) and insoluble dietary fiber (2.29%). There were identified 9 phenolic compounds whereas the chlorogenic and ρ-coumaric acid showed the higher contents (44.23-63.34μg/g and 180.45-707.42μg/g, respectively). Moringa leaves decreased the activity of harmful fecal enzymes (β-glucosidase, β-glucuronidase, tryptophanase and urease up to 40%, 43%, 103% and 266%, respectively) as well tumors incidence in male CD1-mice (~50% with 5% w/v of moringa dose). These findings suggest that the bioactive compounds of moringa such as total dietary fiber and phenolic compounds may have chemopreventive capacity. This is the first study of the suppressive effect of moringa leaves in an in vivo model of AOM/DSS-induced colorectal carcinogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Matricellular Protein CCN1 Promotes Mucosal Healing in Murine Colitis through IL-6

PubMed Central

Choi, Jacob S.; Kim, Ki-Hyun; Lau, Lester F.

2015-01-01

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 Ccn1dm/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. Ccn1dm/dm mice exhibited high mortality, impaired mucosal healing, and diminished IL-6 expression during the repair phase of DSS-induced colitis compared to 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 Ccn1dm/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. PMID:25807183

Colonic eosinophilic inflammation in experimental colitis is mediated by Ly6Chigh CCR2+ inflammatory monocyte/macrophage-derived CCL11

PubMed Central

Waddell, Amanda; Ahrens, Richard; Steinbrecher, Kris; Donovan, Burke; Rothenberg, Marc E.; Munitz, Ariel; Hogan, Simon P.

2011-01-01

Recent genome-wide association studies of pediatric IBD have implicated the 17q12 loci, which contains the eosinophil specific chemokine gene CCL11, with early-onset IBD susceptibility. In the present study, we employed a murine model of experimental colitis to define the molecular pathways that regulate CCL11 expression in the chronic intestinal inflammation and pathophysiology of experimental colitis. Bone marrow chimera experiments showed that hematopoietic cell-derived CCL11 is sufficient for CCL11-mediated colonic eosinophilic inflammation. We show that DSS treatment promotes the recruitment of F4/80+CD11b+CCR2+Ly6Chigh inflammatory monocytes into the colon. F4/80+CD11b+CCR2+Ly6Chigh monocytes express CCL11, and their recruitment positively correlated with colonic eosinophilic inflammation. Phenotypic analysis of purified Ly6Chigh intestinal inflammatory MΦs revealed that these cells express both M1- and M2-associated genes, including Il6, Ccl4 and Cxcl2, and Arg1, Chi3l3, Ccl11 and IL-10, respectively. Attenuation of DSS-induced F4/80+CD11b+CCR2+Ly6Chigh monocyte recruitment to the colon in CCR2−/− mice was associated with decreased colonic CCL11 expression, eosinophilic inflammation and DSS-induced histopathology. These studies identify a mechanism for DSS-induced colonic eosinophilia mediated by Ly6ChighCCR2+ inflammatory monocyte/MΦ-derived CCL11. PMID:21498668

Pharmaceutical Activation or Genetic Absence of ClC-2 Alters Tight Junctions During Experimental Colitis.

PubMed

Jin, Younggeon; Pridgen, Tiffany A; Blikslager, Anthony T

2015-12-01

We have previously reported that the ClC-2 chloride channel has an important role in regulation of tight junction barrier function during experimental colitis, and the pharmaceutical ClC-2 activator lubiprostone initiates intestinal barrier repair in ischemic-injured intestine. Thus, we hypothesized that pharmaceutical ClC-2 activation would have a protective and therapeutic effect in murine models of colitis, which would be absent in ClC-2 mice. We administered lubiprostone to wild-type or ClC-2 mice with dextran sulfate sodium (DSS) or 2, 4, 5-trinitrobenzene sulfonic acid-induced colitis. We determined the severity of colitis and assessed intestinal permeability. Selected tight junction proteins were analyzed by Western blotting and immunofluorescence/confocal microscopy, whereas proliferative and differentiated cells were examined with special staining and immunohistochemistry. Oral preventive or therapeutic administration of lubiprostone significantly reduced the severity of colitis and reduced intestinal permeability in both DSS and trinitrobenzene sulfonic acid-induced colitis. Preventive treatment with lubiprostone induced significant recovery of the expression and distribution of selected sealing tight junction proteins in mice with DSS-induced colitis. In addition, lubiprostone reduced crypt proliferation and increased the number of differentiated epithelial cells. Alternatively, when lubiprostone was administered to ClC-2 mice, the protective effect against DSS colitis was limited. This study suggests a central role for ClC-2 in restoration of barrier function and tight junction architecture in experimental murine colitis, which can be therapeutically targeted with lubiprostone.

Polysaccharide of Hericium erinaceus attenuates colitis in C57BL/6 mice via regulation of oxidative stress, inflammation-related signaling pathways and modulating the composition of the gut microbiota.

PubMed

Ren, Yilin; Geng, Yan; Du, Yan; Li, Wang; Lu, Zhen-Ming; Xu, Hong-Yu; Xu, Guo-Hua; Shi, Jin-Song; Xu, Zheng-Hong

2018-03-16

Inflammatory bowel disease (IBD) is a disease caused by a dysregulated immune with unknown etiology. Hericium erinaceus (H. erinaceus) is a Chinese medicinal fungus, with the effect of prevention and treatment of gastrointestinal disorders. In this study, we have tested the anti-inflammatory effect of polysaccharide of H. erinaceus (HECP, Mw: 86.67 kDa) in the model of dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. Our data indicated that HECP could improve clinical symptoms and down-regulate key markers of oxidative stresses, including nitric oxide (NO), malondialdehyde (MDA), total superoxide dismutase (T-SOD), and myeloperoxidase (MPO). HECP also suppressed the secretion of interleukin (IL)-6, interleukin (IL)-1β, tumor necrosis factor (TNF)-α and the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and decreased the expression of related mRNA. Meanwhile, HECP blocked phosphorylation of nuclear factor-κB (NF-κB) p65, NF-κB inhibitor alpha (IκB-α), mitogen-activated protein kinases (MAPK) and Protein kinase B (Akt) in DSS-treated mice. Moreover, HECP reversed DSS-induced gut dysbiosis and maintained intestinal barrier integrity. In conclusion, HECP ameliorates DSS-induced intestinal injury in mice, which suggests that HECP can serve as a protective dietary nutrient against IBD. Copyright © 2018. Published by Elsevier Inc.

Evaluation of changes in serum chemistry in association with feed withdrawal or high dose oral gavage with Dextran Sodium Sulfate (DSS) induced gut leakage in broiler chickens

USDA-ARS?s Scientific Manuscript database

Dextran sodium sulfate (DSS) has been shown to be effective at inducing enteric inflammation in broiler chickens, resulting in increased leakage of orally administered fluorescein isothiocyanate dextran to circulation. In a previous study, two doses of DSS (0.45g/dose) administered as oral gavage re...

Dietary selenium protects adiponectin knockout mice against chronic inflammation induced colon cancer.

PubMed

Saxena, Arpit; Fayad, Raja; Kaur, Kamaljeet; Truman, Samantha; Greer, Julian; Carson, James A; Chanda, Anindya

2017-04-03

Selenium (Se) is an essential dietary micronutrient that has been examined for protection against different types of cancers including colon cancer. Despite an established inverse association between Se and chronic inflammation induced colon cancer (CICC), the mechanistic understanding of Se's protective effects requires additional in-vivo studies using preclinical animal models of CICC. Adiponectin (APN) is an adipocytokine that is protective against CICC as well. However, its role in the anti-mutagenic effects of the Se-diet remains unknown. To address this knowledge gap, here we examine the ability of dietary Se in reducing CICC in APN knockout mice (KO) and its wild-type C57BL/6. CICC was induced with the colon cancer agent 1,2 dimethyl hydrazine (DMH) along with dextran sodium sulfate (DSS). Se-enhanced diet increased selenoproteins, Gpx-1 and Gpx-2, in the colon tissues, thereby reducing oxidative stress. Se-mediated reduction of CICC was evident from the histopathological studies in both mouse models. In both mice, reduction in inflammation and tumorigenesis associated well with reduced p65 phosphorylation and elevated 53 phosphorylation. Finally, we show that in both models Se-administration promotes goblet cell differentiation with a concomitant increase in the levels of associated proteins, Muc-2 and Math-1. Our findings suggest that Se's protection against CICC involves both colonic epithelial protection and anti-tumor effects that are independent of APN.

Deep Space Station (DSS-13) automation demonstration

NASA Technical Reports Server (NTRS)

Remer, D. S.; Lorden, G.

1980-01-01

The data base collected during a six month demonstration of an automated Deep Space Station (DSS 13) run unattended and remotely controlled is summarized. During this period, DSS 13 received spacecraft telemetry data from Voyager, Pioneers 10 and 11, and Helios projects. Corrective and preventive maintenance are reported by subsystem including the traditional subsystems and those subsystems added for the automation demonstration. Operations and maintenance data for a comparable manned Deep Space Station (DSS 11) are also presented for comparison. The data suggests that unattended operations may reduce maintenance manhours in addition to reducing operator manhours. Corrective maintenance for the unmanned station was about one third of the manned station, and preventive maintenance was about one half.

Development of a decision support system for monitoring, reporting and forecasting ecological conditions of the Appalachian Trail

USGS Publications Warehouse

Wang, Yeqiao; Nemani, Ramakrishna; Dieffenbach, Fred; Stolte, Kenneth; Holcomb, Glenn B.; Robinson, Matt; Reese, Casey C.; McNiff, Marcia; Duhaime, Roland; Tierney, Geri; Mitchell, Brian; August, Peter; Paton, Peter; LaBash, Charles

2010-01-01

This paper introduces a collaborative multi-agency effort to develop an Appalachian Trail (A.T.) MEGA-Transect Decision Support System (DSS) for monitoring, reporting and forecasting ecological conditions of the A.T. and the surrounding lands. The project is to improve decisionmaking on management of the A.T. by providing a coherent framework for data integration, status reporting and trend analysis. The A.T. MEGA-Transect DSS is to integrate NASA multi-platform sensor data and modeling through the Terrestrial Observation and Prediction System (TOPS) and in situ measurements from A.T. MEGA-Transect partners to address identified natural resource priorities and improve resource management decisions.

New approaches for real time decision support systems

NASA Technical Reports Server (NTRS)

Hair, D. Charles; Pickslay, Kent

1994-01-01

NCCOSC RDT&E Division (NRaD) is conducting research into ways of improving decision support systems (DSS) that are used in tactical Navy decision making situations. The research has focused on the incorporation of findings about naturalistic decision-making processes into the design of the DSS. As part of that research, two computer tools were developed that model the two primary naturalistic decision-making strategies used by Navy experts in tactical settings. Current work is exploring how best to incorporate the information produced by those tools into an existing simulation of current Navy decision support systems. This work has implications for any applications involving the need to make decisions under time constraints, based on incomplete or ambiguous data.

A framework for ecological decision support systems: Building the right systems and building the systems right

USGS Publications Warehouse

D'Erchia, Frank; Korschgen, Carl E.; Nyquist, M.; Root, Ralph; Sojda, Richard S.; Stine, Peter

2001-01-01

Workshops in the late 1990's launched the commitment of the U.S. Geological Survey's Biological Resources Division (BRD) to develop and implement decision support systems (DSS) applications. One of the primary goals of this framework document is to provide sufficient background and information for Department of the Interior (DOI) bureau stakeholders and other clients to determine the potential for DSS development. Such an understanding can assist them in carrying out effective land planning and management practices. This document provides a definition of DSS and its characteristics and capabilities. It proceeds to describe issues related to meeting resource managers needs, such as the needs for specific applications, customer requirements, information and technology transfer, user support, and institutionalization. Using the decision process as a means to guide DSS development and determine users needs is also discussed. We conclude with information on method to evaluate DSS development efforts and recommended procedures for verification and validation. 

A Framework for a Decision Support System in a Hierarchical Extended Enterprise Decision Context

NASA Astrophysics Data System (ADS)

Boza, Andrés; Ortiz, Angel; Vicens, Eduardo; Poler, Raul

Decision Support System (DSS) tools provide useful information to decision makers. In an Extended Enterprise, a new goal, changes in the current objectives or small changes in the extended enterprise configuration produce a necessary adjustment in its decision system. A DSS in this context must be flexible and agile to make suitable an easy and quickly adaptation to this new context. This paper proposes to extend the Hierarchical Production Planning (HPP) structure to an Extended Enterprise decision making context. In this way, a framework for DSS in Extended Enterprise context is defined using components of HPP. Interoperability details have been reviewed to identify the impact in this framework. The proposed framework allows overcoming some interoperability barriers, identifying and organizing components for a DSS in Extended Enterprise context, and working in the definition of an architecture to be used in the design process of a flexible DSS in Extended Enterprise context which can reuse components for futures Extended Enterprise configurations.

The GBT Dynamic Scheduling System: Development and Testing

NASA Astrophysics Data System (ADS)

McCarty, M.; Clark, M.; Marganian, P.; O'Neil, K.; Shelton, A.; Sessoms, E.

2009-09-01

During the summer trimester of 2008, all observations on the Robert C. Byrd Green Bank Telescope (GBT) were scheduled using the new Dynamic Scheduling System (DSS). Beta testing exercised the policies, algorithms, and software developed for the DSS project. Since observers are located all over the world, the DSS was implemented as a web application. Technologies such as iCalendar, Really Simple Syndication (RSS) feeds, email, and instant messaging are used to transfer as much or as little information to observers as they request. We discuss the software engineering challenges leading to our implementation such as information distribution and building rich user interfaces in the web browser. We also relate our adaptation of agile development practices to design and develop the DSS. Additionally, we describe handling differences in expected versus actual initial conditions in the pool of project proposals for the 08B trimester. We then identify lessons learned from beta testing and present statistics on how the DSS was used during the trimester.

A pilot Diabetic Support Service based on family practice attenders: comparison with diabetic clinics in east London.

PubMed

Boucher, B J; Claff, H R; Edmonson, M; Evans, S; Harris, B T; Hull, S A; Jones, E J; Mellins, D H; Safir, J G; Taylor, B

1987-01-01

A pilot Diabetic Support Service (DSS) based on a computer register was devised for diabetic patients identified within three group practices in an inner city district of London. Of 159 eligible diabetics, 142 were followed over 2 years. Glycosylated haemoglobin (GHb) monitoring and adequacy of clinic reviews were audited. Care achieved by the DSS was compared with conventional Diabetic Clinic (DC) management of a sample of 200 diabetics from the same district. Serial GHb measurements were made on 66.2% of DSS and 44.5% of DC patients: GHb fell significantly only in DSS patients (13.1% to 11.4%). Proportional falls in GHb were comparable in each DSS treatment group (diet alone, oral hypoglycaemic agents, and insulin) and for hospital attenders and non-attenders equally. The planned clinical reviews were achieved in 40.1% of DSS patients entered (29% GP only, 54% of clinic attenders) and in 15% of DC patients (plus 75% fundal and blood pressure examination). The study led to provision of a formal diabetic clinic annual review system, diabetic mini-clinics in two of the three group practices, and the appointment of two Diabetic Liaison Sisters. With administrative simplification the system is to be made available to all diabetics in the District through their GPs during 1986-8.

Puberty is delayed in male mice with dextran sodium sulfate colitis out of proportion to changes in food intake, body weight, and serum levels of leptin.

PubMed

Deboer, Mark D; Li, Yongli

2011-01-01

In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the prepuce from the glans penis as a marker of pubertal progression. Compared with free-feeding control mice, DSS and FR mice had significantly lower weight on d 7-10 of treatment. DSS mice had later puberty than control and FR mice. DSS mice also had smaller testes, lower FSH levels, increased systemic cytokines, and increased colonic inflammation by histology. Leptin levels were similar between DSS and FR mice, whereas both had decreases in leptin compared with controls. We conclude that DSS colitis causes delayed puberty in sexually immature male mice beyond what is seen among FR mice of similar weight, food intake, and leptin levels. These experiments provide support for the hypothesis that pubertal delay in colitis is influenced by factors beyond poor weight gain alone.

Skull Base Invasion Patterns and Survival Outcomes of Nonmelanoma Skin Cancers

PubMed Central

Dundar, Yusuf; Cannon, Richard B.; Monroe, Marcus M.; Buchmann, Luke Oliver; Hunt, Jason Patrick

2016-01-01

Objective Report routes of skull base invasion for head and neck nonmelanoma skin cancers (NMSCs) and their survival outcomes. Design Retrospective. Participants Ninety patients with NMSC with skull base invasion between 2004 and 2014. Major Outcome Measures Demographic, tumor characteristics, and treatments associated with different types of skull base invasion and disease-specific survival (DSS) and overall survival (OS). Results Perineural invasion (PNI) to the skull base occurred in 69% of patients, whereas 38% had direct skull base invasion. Age, histology, orbital invasion, active immunosuppression, cranial nerve (CN) involved, and type of skull base invasion were significantly associated with DSS and OS (p < 0.05). Patients with basal cell carcinoma (BCC) had significantly improved DSS and OS compared with other histologies (p < 0.05). Patients with CN V PNI had significantly improved DSS and OS compared with CN VII PNI (p < 0.05). Patients with zone II PNI had significantly improved DSS and OS compared with those with direct invasion or zone III PNI (p < 0.05). Nonsurgical therapy was rarely used and is associated with a reduction in DSS and OS (p < 0.05). Conclusion Patterns and survival outcomes for NMSC skull base invasion are reported. Zone II PNI, BCC, and CN V PNI are associated with improved survival outcomes. PMID:28321381

Krüppel-Like Factor 5 Protects Against Dextran Sulfate Sodium-Induced Colonic Injury by Promoting Epithelial Repair in Mice

PubMed Central

McConnell, Beth B.; Kim, Samuel S.; Bialkowska, Agnieszka B.; Yu, Ke; Sitaraman, Shanthi V.; Yang, Vincent. W.

2010-01-01

BACKGROUND & AIMS Krüppel-like factor 5 (KLF5) is a transcription factor that promotes proliferation; is highly expressed in dividing crypt cells of the gastrointestinal epithelium and is induced by various stress stimuli. We sought to determine the role of KLF5 in colonic inflammation and recovery by studying mice with dextran sulfate sodium (DSS)-induced colitis. METHODS Wild-type (WT) and Klf5+/− mice were given DSS in the drinking water to induce colitis. For recovery experiments, mice were given normal drinking water for 5 days after DSS administration. The extent of colitis was determined using established clinical and histological scoring systems. Immunohistochemical and immunoblotting analyses were used to examine proliferation, migration, and expression of the epidermal growth factor receptor (EGFR). RESULTS Klf5 expression was increased in colonic tissues of WT mice given DSS; induction of Klf5 was downstream of mitogen-activated protein kinase signaling. In DSS-induced colitis, Klf5+/− mice exhibited greater sensitivity to DSS than WT mice, with significantly higher clinical and histological colitis scores. In recovery experiments, Klf5+/− mice showed poor recovery, with continued weight loss and higher mortality than WT mice. Klf5+/− mice from the recovery period had reduced epithelial proliferation and cell migration at sites of ulceration compared to WT mice; these reductions correlated with reduced expression of EGFR. CONCLUSIONS Epithelial repair is an important aspect of recovery from DSS-induced colitis. The transcription factor KLF5 regulates mucosal healing through its effects on epithelial proliferation and migration. PMID:21078320

Development and testing of a scale to assess physician attitudes about handheld computers with decision support.

PubMed

Ray, Midge N; Houston, Thomas K; Yu, Feliciano B; Menachemi, Nir; Maisiak, Richard S; Allison, Jeroan J; Berner, Eta S

2006-01-01

The authors developed and evaluated a rating scale, the Attitudes toward Handheld Decision Support Software Scale (H-DSS), to assess physician attitudes about handheld decision support systems. The authors conducted a prospective assessment of psychometric characteristics of the H-DSS including reliability, validity, and responsiveness. Participants were 82 Internal Medicine residents. A higher score on each of the 14 five-point Likert scale items reflected a more positive attitude about handheld DSS. The H-DSS score is the mean across the fourteen items. Attitudes toward the use of the handheld DSS were assessed prior to and six months after receiving the handheld device. Cronbach's Alpha was used to assess internal consistency reliability. Pearson correlations were used to estimate and detect significant associations between scale scores and other measures (validity). Paired sample t-tests were used to test for changes in the mean attitude scale score (responsiveness) and for differences between groups. Internal consistency reliability for the scale was alpha = 0.73. In testing validity, moderate correlations were noted between the attitude scale scores and self-reported Personal Digital Assistant (PDA) usage in the hospital (correlation coefficient = 0.55) and clinic (0.48), p < 0.05 for both. The scale was responsive, in that it detected the expected increase in scores between the two administrations (3.99 (s.d. = 0.35) vs. 4.08, (s.d. = 0.34), p < 0.005). The authors' evaluation showed that the H-DSS scale was reliable, valid, and responsive. The scale can be used to guide future handheld DSS development and implementation.

Surgical Outcomes of Deep Superior Sulcus Augmentation Using Acellular Human Dermal Matrix in Anophthalmic or Phthisis Socket.

PubMed

Cho, Won-Kyung; Jung, Su-Kyung; Paik, Ji-Sun; Yang, Suk-Woo

2016-07-01

Patients with anophthalmic or phthisis socket suffer from cosmetic problems. To resolve those problems, the authors present the surgical outcomes of deep superior sulcus (DSS) augmentation using acellular dermal matrix in patients with anophthalmic or phthisis socket. The authors retrospectively reviewed anophthalmic or phthisis patients who underwent surgery for DSS augmentation using acellular dermal matrix. To evaluate surgical outcomes, the authors focused on 3 aspects: the possibility of wearing contact prosthesis, the degree of correction of the DSS, and any surgical complications. The degree of correction of DSS was classified as excellent: restoration of superior sulcus enough to remove sunken sulcus shadow; fair: gain of correction effect but sunken shadow remained; or fail: no effect of correction at all. Ten eyes of 10 patients were included. There was a mean 21.3 ± 37.1-month period from evisceration or enucleation to the operation for DSS augmentation. All patients could wear contact prosthesis after the operation (100%). The degree of correction was excellent in 8 patients (80%) and fair in 2. Three of 10 (30%) showed complications: eyelid entropion, upper eyelid multiple creases, and spontaneous wound dehiscence followed by inflammation after stitch removal. Uneven skin surface and paresthesia in the forehead area of the affected eye may be observed after surgery. The overall surgical outcomes were favorable, showing an excellent degree of correction of DSS and low surgical complication rates. This procedure is effective for patients who have DSS in the absence or atrophy of the eyeball.

Curcuma longa Extract Exerts a Myorelaxant Effect on the Ileum and Colon in a Mouse Experimental Colitis Model, Independent of the Anti-Inflammatory Effect

PubMed Central

Roda, Giulia; Micucci, Matteo; Ioan, Pierfranco; D’Errico-Grigioni, Antonia; Sartini, Alessandro; Guidetti, Elena; Marocchi, Margherita; Cevenini, Monica; Rosini, Francesca; Montagnani, Marco; Chiarini, Alberto; Mazzella, Giuseppe

2012-01-01

Background Curcuma has long been used as an anti-inflammatory agent in inflammatory bowel disease. Since gastrointestinal motility is impaired in inflammatory states, the aim of this work was to evaluate if Curcuma Longa had any effect on intestinal motility. Methods The biological activity of Curcuma extract was evaluated against Carbachol induced contraction in isolated mice intestine. Acute and chronic colitis were induced in Balb/c mice by Dextran Sulphate Sodium administration (5% and 2.5% respectively) and either Curcuma extract (200 mg/kg/day) or placebo was thereafter administered for 7 and 21 days respectively. Spontaneous contractions and the response to Carbachol and Atropine of ileum and colon were studied after colitis induction and Curcuma administration. Results Curcuma extract reduced the spontaneous contractions in the ileum and colon; the maximal response to Carbachol was inhibited in a non-competitive and reversible manner. Similar results were obtained in ileum and colon from Curcuma fed mice. DSS administration decreased the motility, mainly in the colon and Curcuma almost restored both the spontaneous contractions and the response to Carbachol after 14 days assumption, compared to standard diet, but a prolonged assumption of Curcuma decreased the spontaneous and Carbachol-induced contractions. Conclusions Curcuma extract has a direct and indirect myorelaxant effect on mouse ileum and colon, independent of the anti-inflammatory effect. The indirect effect is reversible and non-competitive with the cholinergic agent. These results suggest the use of curcuma extract as a spasmolytic agent. PMID:22984538

Impact of toll-like-receptor-9 (TLR9) deficiency on visceral adipose tissue adipokine expression during chronic DSS-induced colitis in mice.

PubMed

Karrasch, T; Schmid, A; Kopp, A; Obermeier, F; Hofmann, C; Schäffler, A

2015-02-01

Studies postulate an involvement of adipokines in inflammatory gastrointestinal diseases. Leptin-deficient ob/ob mice as well as TLR9-deficient mice have a more moderate course of chronic DSS-induced colitis (DSS-CC) and adipocytes do express functional TLR9 molecules. Adipokine mRNA expression in visceral adipose tissue of mice before and after the induction of DSS-CC was investigated. Experiments were performed in both TLR9(wt/wt) and TLR9(-/-) mice. In vitro, the effect of TLR9 blocking peptide on leptin and visfatin protein secretion was studied in 3T3-L1 adipocytes. Induction of DSS-CC led to an upregulation of leptin mRNA expression in TLR9(wt/wt) mice, while TLR9(-/-) animals showed a significant reduction of leptin expression even below baseline. While visfatin expression remained unchanged in TLR9(wt/wt) animals, TLR9(-/-) mice exhibited a significant induction during DSS-CC. CTRP-3 expression was reduced after colitis induction only in TLR9(-/-) animals. Of note, IL-6 expression levels remained unchanged, while CXCL1/KC and cyclophilin A expression was reduced in DSS-CC. Inhibition of TLR9 signaling by using TLR9 blocking peptide led to reduced leptin protein secretion into cell culture supernatants in 3T3-L1 adipocytes, while visfatin protein secretion was enhanced. DSS-CC leads to differential adipokine expression profiles in the visceral fat pad in TLR9(wt/wt) vs. TLR9(-/-) mice. In vitro, inhibition of TLR9 signaling induces visfatin secretion while inhibiting leptin secretion in adipocytes. Thus, visceral adipokines are regulated by intact TLR9 signaling pathway and a specific interplay between the leptin- and the TLR9-pathways might be of pathophysiological importance in chronic intestinal inflammation. © Georg Thieme Verlag KG Stuttgart · New York.

Loss of Dok-1 and Dok-2 in mice causes severe experimental colitis accompanied by reduced expression of IL-17A and IL-22

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waseda, Masazumi; Arimura, Sumimasa; Shimura, Eri

Appropriate immune responses and mucosal barrier functions are required for the maintenance of intestinal homeostasis. Defects in this defense system may lead to inflammatory disorders such as inflammatory bowel disease. Downstream of tyrosine kinases 1 (Dok-1) and its closest homolog, Dok-2, are preferentially expressed in immune cells, and play essential roles in the negative regulation of multiple signaling pathways in both innate and adaptive immunity. However, the function of these proteins in intestinal homeostasis remained unclear. Here we show that Dok-1/-2 double knockout (DKO) mice were highly susceptible to dextran sodium sulfate (DSS)-induced colitis compared with Dok-1 or Dok-2 singlemore » KO and wild type (WT) mice. Furthermore, DSS-treated Dok-1/-2 DKO mice exhibited increased colonic tissue damage accompanied by reduced proliferation of the epithelial cells relative to WT controls, suggesting that Dok-1/-2 DKO mice have defects in the repair of intestinal epithelial lesions. In addition, the levels of the Th17 cytokines IL-17A and IL-22, which have protective roles in DSS-induced colitis, were reduced in DSS-treated Dok-1/-2 DKO mice compared with WT mice. Taken together, our results demonstrate that Dok-1 and Dok-2 negatively regulate intestinal inflammation, apparently through the induction of IL-17A and IL-22 expression. - Highlights: • Dok-1 and Dok-2 play a cooperative role in protection against DSS-induced colitis. • Dok-1/-2 double KO (DKO) mice show extensive ulceration of the colon after DSS treatment. • Proliferation of colonic epithelium is inhibited in DSS-treated Dok-1/-2 DKO mice. • Expression of IL-17A and IL-22 is reduced in the colon of DSS-treated Dok-1/-2 DKO mice.« less

Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in mice

USDA-ARS?s Scientific Manuscript database

Methylthioadenosine (MTA) is a precursor of the methionine salvage pathway and has been shown to have anti-inflammatory properties in various models of acute and chronic inflammation. However, the anti-inflammatory properties of MTA in models of intestinal inflammation are not defined. We hypothesiz...

A Statistical Model-Based Decision Support System for Managing Summer Stream Temperatures with Quantified Confidence Analysis

NASA Astrophysics Data System (ADS)

Neumann, D. W.; Zagona, E. A.; Rajagopalan, B.

2005-12-01

Warm summer stream temperatures due to low flows and high air temperatures are a critical water quality problem in many western U.S. river basins because they impact threatened fish species' habitat. Releases from storage reservoirs and river diversions are typically driven by human demands such as irrigation, municipal and industrial uses and hydropower production. Historically, fish needs have not been formally incorporated in the operating procedures, which do not supply adequate flows for fish in the warmest, driest periods. One way to address this problem is for local and federal organizations to purchase water rights to be used to increase flows, hence decrease temperatures. A statistical model-predictive technique for efficient and effective use of a limited supply of fish water has been developed and incorporated in a Decision Support System (DSS) that can be used in an operations mode to effectively use water acquired to mitigate warm stream temperatures. The DSS is a rule-based system that uses the empirical, statistical predictive model to predict maximum daily stream temperatures based on flows that meet the non-fish operating criteria, and to compute reservoir releases of allocated fish water when predicted temperatures exceed fish habitat temperature targets with a user specified confidence of the temperature predictions. The empirical model is developed using a step-wise linear regression procedure to select significant predictors, and includes the computation of a prediction confidence interval to quantify the uncertainty of the prediction. The DSS also includes a strategy for managing a limited amount of water throughout the season based on degree-days in which temperatures are allowed to exceed the preferred targets for a limited number of days that can be tolerated by the fish. The DSS is demonstrated by an example application to the Truckee River near Reno, Nevada using historical flows from 1988 through 1994. In this case, the statistical model predicts maximum daily Truckee River stream temperatures in June, July, and August using predicted maximum daily air temperature and modeled average daily flow. The empirical relationship was created using a step-wise linear regression selection process using 1993 and 1994 data. The adjusted R2 value for this relationship is 0.91. The model is validated using historic data and demonstrated in a predictive mode with a prediction confidence interval to quantify the uncertainty. Results indicate that the DSS could substantially reduce the number of target temperature violations, i.e., stream temperatures exceeding the target temperature levels detrimental to fish habitat. The results show that large volumes of water are necessary to meet a temperature target with a high degree of certainty and violations may still occur if all of the stored water is depleted. A lower degree of certainty requires less water but there is a higher probability that the temperature targets will be exceeded. Addition of the rules that consider degree-days resulted in a reduction of the number of temperature violations without increasing the amount of water used. This work is described in detail in publications referenced in the URL below.

Simulation of specific conductance and chloride concentration in Abercorn Creek, Georgia, 2000-2009

USGS Publications Warehouse

Conrads, Paul; Roehl, Edwin A.; Davie, Steven R.

2011-01-01

The City of Savannah operates an industrial and domestic water-supply intake on Abercorn Creek approximately 2 miles from the confluence with the Savannah River upstream from the Interstate 95 bridge. Chloride concentrations are a major concern for the city because industrial customers require water with low chloride concentrations, and elevated chloride concentrations require additional water treatment in order to meet those needs. The proposed deepening of Savannah Harbor could increase chloride concentrations (the major ion in seawater) in the upper reaches of the lower Savannah River estuary, including Abercorn Creek. To address this concern, mechanistic and empirical modeling approaches were used to simulate chloride concentrations at the city's intake to evaluate potential effects from deepening the Savannah Harbor. The first approach modified the mechanistic Environmental Fluid Dynamics Code (EFDC) model developed by Tetra Tech and used for evaluating proposed harbor deepening effects for the Environmental Impact Statement. Chloride concentrations were modeled directly with the EFDC model as a conservative tracer. This effort was done by Tetra Tech under a separate funding agreement with the U.S. Army Corps of Engineers and documented in a separate report. The second approach, described in this report, was to simulate chloride concentrations by developing empirical models from the available data using artificial neural network (ANN) and linear regression models. The empirical models used daily streamflow, specific conductance (field measurement for salinity), water temperature, and water color time series for inputs. Because there are only a few data points that describe the relation between high specific conductance values at the Savannah River at Interstate 95 and the water plant intake, there was a concern that these few data points would determine the extrapolation of the empirical model and potentially underestimate the effect of deepening the harbor on chloride concentrations at the intake. To accommodate these concerns, two ANN chloride models were developed for the intake. The first model (ANN M1e) used all the data. The second model (ANN M2e) only used data when specific conductance at Interstate 95 was less than 175 microsiemens per centimeter at 25 degrees Celsius. Deleting the conductivity data greater than 175 microsiemens per centimeter removed the "plateau" effect observed in the data. The chloride simulations with the ANN M1 model have a low sensitivity to specific conductance (salinity) at Interstate 95, whereas the chloride simulations with the ANN M2 model have a high sensitivity to salinity at Interstate 95. The two modeling approaches (Tetra Tech's EFDC model and the one described in this report) were integrated into a decision support system (DSS) that combines the historical database, output from EFDC, ANN models, ANN model simulation controls, streaming graphics, and model output. The DSS was developed as a Microsoft ExcelTM/Visual Basic for Applications program, which allowed the DSS to be prototyped, easily modified, and distributed in a familiar spreadsheet format. The EFDC and ANN models were used to simulate various harbor deepening scenarios. To accommodate the geometry changes in the harbor, the ANN models used the EFDC model-simulated salinity changes for a historical condition as input. The DSS uses a graphical user interface and allows the user to interrogate the ANN models and EFDC output. Two scenarios were simulated using the Savannah Chloride Model DSS to demonstrate different input options. One scenario decreased winter streamflows to a constant streamflow for 45 days. Streamflows during the period January 1 to February 15 were set to a constant 3,600 cubic feet per second for the simulation period of October 1, 2006, to October 1, 2009. The decreased winter streamflow resulted in predictions of increased specific conductance by as much as 50 microsiemens per centimeter and chlorid

Dissipative vector soliton in a dispersion-managed fiber laser with normal dispersion.

PubMed

Wang, Siming; Fan, Xuliang; Zhao, Luming; Wang, Yong; Tang, Dingyuan; Shen, Deyuan

2014-12-10

We numerically study the vector dynamics of dissipative solitons (DSs) in a 2 μm dispersion-managed fiber laser mode locked by a semiconductor saturable absorber mirror and operated in the normal dispersion regime. It is shown that the effective gain bandwidth is crucial for the DS generation. The steep spectral edges of DSs are the consequence of the interaction among the normal dispersion, fiber nonlinearity, gain and loss, and gain dispersion effect, etc. We numerically duplicate the experimental results and further explore the vector features of the generated DSs. Two DSs formed along the two orthogonal polarization directions which, incoherently coupled with each other, could propagate in the birefringent cavity with the same group velocity.

A Decision Support System for Optimum Use of Fertilizers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoskinson, Reed Louis; Hess, John Richard; Fink, Raymond Keith

1999-07-01

The Decision Support System for Agriculture (DSS4Ag) is an expert system being developed by the Site-Specific Technologies for Agriculture (SST4Ag) precision farming research project at the INEEL. DSS4Ag uses state-of-the-art artificial intelligence and computer science technologies to make spatially variable, site-specific, economically optimum decisions on fertilizer use. The DSS4Ag has an open architecture that allows for external input and addition of new requirements and integrates its results with existing agricultural systems’ infrastructures. The DSS4Ag reflects a paradigm shift in the information revolution in agriculture that is precision farming. We depict this information revolution in agriculture as an historic trend inmore » the agricultural decision-making process.« less

A Decision Support System for Optimum Use of Fertilizers

DOE Office of Scientific and Technical Information (OSTI.GOV)

R. L. Hoskinson; J. R. Hess; R. K. Fink

1999-07-01

The Decision Support System for Agriculture (DSS4Ag) is an expert system being developed by the Site-Specific Technologies for Agriculture (SST4Ag) precision farming research project at the INEEL. DSS4Ag uses state-of-the-art artificial intelligence and computer science technologies to make spatially variable, site-specific, economically optimum decisions on fertilizer use. The DSS4Ag has an open architecture that allows for external input and addition of new requirements and integrates its results with existing agricultural systems' infrastructures. The DSS4Ag reflects a paradigm shift in the information revolution in agriculture that is precision farming. We depict this information revolution in agriculture as an historic trend inmore » the agricultural decision-making process.« less

Association between sex, nutritional status, severity of dengue hemorrhagic fever, and immune status in infants with dengue hemorrhagic fever.

PubMed

Nguyen, Thanh Hung; Nguyen, Trong Lan; Lei, Huan-Yao; Lin, Yee-Shin; Le, Bich Lien; Huang, Kao-Jean; Lin, Chiou-Feng; Do, Quang Ha; Vu, Thi Que Huong; Lam, Thi My; Yeh, Trai-Ming; Huang, Jyh-Hsiung; Liu, Ching-Chuan; Halstead, Scott B

2005-04-01

The association between sex, nutritional status, and the severity of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), and immune status was investigated in 245 Vietnamese infants with predominantly primary infections with dengue virus. Male and female infants were at equal risk of developing DHF/DSS. However, infants of low height and weight for age were under-represented among DHF/DSS cases compared with 533 healthy baby clinic infant controls. Acute illness phase blood levels of selected cytokines (interferon-gamma and tumor necrosis factor-alpha) and serum levels of antibodies to dengue virus were elevated in the same range in male and female infants with DHF/DSS, as well as in infants with and without malnutrition.

Accelerated corrosion of 2205 duplex stainless steel caused by marine aerobic Pseudomonas aeruginosa biofilm.

PubMed

Xu, Dake; Xia, Jin; Zhou, Enze; Zhang, Dawei; Li, Huabing; Yang, Chunguang; Li, Qi; Lin, Hai; Li, Xiaogang; Yang, Ke

2017-02-01

Microbiologically influenced corrosion (MIC) of 2205 duplex stainless steel (DSS) in the presence of Pseudomonas aeruginosa was investigated through electrochemical and surface analyses. The electrochemical results showed that P. aeruginosa significantly reduced the corrosion resistance of 2205 DSS. Confocal laser scanning microscopy (CLSM) images showed that the depths of the largest pits on 2205 DSS with and without P. aeruginosa were 14.0 and 4.9μm, respectively, indicating that the pitting corrosion was accelerated by P. aeruginosa. X-ray photoelectron spectroscopy (XPS) results revealed that CrO 3 and CrN formed on the 2205 DSS surface in the presence of P. aeruginosa. Copyright © 2016 Elsevier B.V. All rights reserved.

DSS 13 frequency stability tests performed during May 1985 through March 1986

NASA Technical Reports Server (NTRS)

Otoshi, T. Y.; Franco, M. M.

1986-01-01

Results of station frequency stability testing performed at DSS 13 (Deep Space Station) during May 1985 through March 1986 are presented. The testing was done on X-band uplink and X- and S-band downlink subsystems as well as on end-to-end systems. The subsystem test data are useful for assessing the frequency stability of various prototype X-band uplink or downlink subsystems for purposes of making design improvements. Information derived from extensive testing at DSS 13 will be useful in the preparation of an X-band Uplink Demonstration Experiment to be conducted at DSS 13, and will also be valuable in the preparations of gravity wave experiments to be conducted at other DSN stations in the future.

Induction of dsRNA-activated protein kinase links mitochondrial unfolded protein response to the pathogenesis of intestinal inflammation.

PubMed

Rath, Eva; Berger, Emanuel; Messlik, Anja; Nunes, Tiago; Liu, Bo; Kim, Sandy C; Hoogenraad, Nick; Sans, Miquel; Sartor, R Balfour; Haller, Dirk

2012-09-01

Inflammatory bowel diseases (IBDs) feature multiple cellular stress responses, including endoplasmic reticulum (ER) unfolded protein responses (UPRs). UPRs represent autoregulatory pathways that adjust organelle capacity to cellular demand. A similar mechanism, mitochondrial UPR (mtUPR), has been described for mitochondria. ER UPR in intestinal epithelial cells (IECs) contributes to the development of intestinal inflammation, and since mitochondrial alterations and dysfunction are implicated in the pathogenesis of IBDs, the authors characterised mtUPR in the context of intestinal inflammation. Truncated ornithine transcarbamylase was used to selectively induce mtUPR in a murine IEC line. Dextran sodium sulphate (DSS) was administered to PKR (double-stranded-RNA-activated protein kinase) knockout mice to induce IEC stress in vivo and to test for their susceptibility to DSS-induced colitis. Expression levels of the mitochondrial chaperone chaperonin 60 (CPN60) and PKR were quantified in IECs from patients with IBDs and from murine models of colitis using immunohistochemistry and Western blot analysis. Selective mtUPR induction by truncated ornithine transcarbamylase transfection triggered the phosphorylation of eukaryotic translation initiation factor (eIF) 2α and cJun through the recruitment of PKR. Using pharmacological inhibitors and small inhibitory RNA, the authors identified mtUPR-induced eIF2α phosphorylation and transcription factor activation (cJun/AP1) as being dependent on the activities of the mitochondrial protease ClpP and the cytoplasmic kinase PKR. Pkr(-/-) mice failed to induce CPN60 in IECs upon DSS treatment at early time points and subsequently showed an almost complete resistance to DSS-induced colitis. Under inflammatory conditions, primary IECs from patients with IBDs and two murine models of colitis exhibited a strong induction of the mtUPR marker protein CPN60 associated with enhanced expression of PKR. PKR integrates mtUPR into the disease-relevant ER UPR via eIF2α phosphorylation and AP1 activation. Induction of mtUPR and PKR was observed in IECs from murine models and patients with IBDs. The authors' results indicate that PKR might link mitochondrial stress to intestinal inflammation.

Deep seismic exploration into the Arctic Lithosphere: Arctic-2012 Russian wide-angle seismic experiment

NASA Astrophysics Data System (ADS)

Kashubin, S.

2013-12-01

Integrated geological and geophysical studies of the Earth's crust and upper mantle (the Russian project 'Arctic-2012') were carried out in 2012 in the Mendeleev Rise, central Arctic. The set of studies included wide-angle seismic observations along the line crossing the Mendeleev Rise in its southern part. The DSS seismic survey was aimed at the determination of the Mendeleev Rise crust type. A high-power air gun (120 liters or 7320 cu.in) and ocean stations with multi-component recording (X, Y, Z geophone components and a hydrophone) were used for the DSS. The line was studied using a dense system of observation: bottom station spacing was from 10 to 20 km, excitation point spacing (seismic traces interval) was 315 m. Observation data were obtained in 27 location points of bottom stations, the distance between the first and the last stations was 480 km, the length of the excitation line was 740 km. In DSS wave fields, in the first and later arrivals, there are refracted and reflected waves associated with boundaries in the sedimentary cover, with the top of the basement, and with boundaries in the consolidated crust, including its bottom (Moho discontinuity). The waves could be traced for offsets up to 170-240 km. The DSS line coincides with the near-vertical CMP line worked out with the use of a 4500-m-long seismic streamer and with a 50 m shot point interval that allowed essential detalization of the upper part of the section and taking it into account in the construction of a deep crust model. The deep velocity model was constructed using ray-trace modeling of compressional, shear, and converted waves with the use of the SeisWide program. Estimates were obtained for Vp/Vs velocity ratios, which played an important role in determining the type of crust. The results of the interpretation show that the Mendeleev Rise section corresponds to sections of a thin continental crust of shelf seas and a thinned continental crust of submarine ridges and rises.

Construction and Resource Utilization Explorer (CRUX): Implementing Instrument Suite Data Fusion to Characterize Regolith Hydrogen Resources

NASA Technical Reports Server (NTRS)

Haldemann, Albert F. C.; Johnson, Jerome B.; Elphic, Richard C.; Boynton, William V.; Wetzel, John

2006-01-01

CRUX is a modular suite of geophysical and borehole instruments combined with display and decision support system (MapperDSS) tools to characterize regolith resources, surface conditions, and geotechnical properties. CRUX is a NASA-funded Technology Maturation Program effort to provide enabling technology for Lunar and Planetary Surface Operations (LPSO). The MapperDSS uses data fusion methods with CRUX instruments, and other available data and models, to provide regolith properties information needed for LPSO that cannot be determined otherwise. We demonstrate the data fusion method by showing how it might be applied to characterize the distribution and form of hydrogen using a selection of CRUX instruments: Borehole Neutron Probe and Thermal Evolved Gas Analyzer data as a function of depth help interpret Surface Neutron Probe data to generate 3D information. Secondary information from other instruments along with physical models improves the hydrogen distribution characterization, enabling information products for operational decision-making.

Toll-like receptor 3 pre-conditioning increases the therapeutic efficacy of umbilical cord mesenchymal stromal cells in a dextran sulfate sodium-induced colitis model.

PubMed

Fuenzalida, Patricia; Kurte, Mónica; Fernández-O'ryan, Catalina; Ibañez, Cristina; Gauthier-Abeliuk, Melanie; Vega-Letter, Ana María; Gonzalez, Paz; Irarrázabal, Carlos; Quezada, Nataly; Figueroa, Fernando; Carrión, Flavio

2016-05-01

Immunomodulatory properties of human umbilical cord-derived mesenchymal stromal cells (UCMSCs) can be differentially modulated by toll-like receptors (TLR) agonists. Here, the therapeutic efficacy of short TLR3 and TLR4 pre-conditioning of UCMSCs was evaluated in a dextran sulfate sodium (DSS)-induced colitis in mice. The novelty of this study is that although modulation of human MSCs activity by TLRs is not a new concept, this is the first time that short TLR pre-conditioning has been carried out in a murine inflammatory model of acute colitis. C57BL/6 mice were exposed to 2.5% dextran sulfate sodium (DSS) in drinking water ad libitum for 7 days. At days 1 and 3, mice were injected intraperitoneally with 1 × 10(6) UCMSCs untreated or TLR3 and TLR4 pre-conditioned UCMSCs. UCMSCs were pre-conditioned with poly(I:C) for TLR3 and LPS for TLR4 for 1 h at 37°C and 5% CO2. We evaluated clinical signs of disease and body weights daily. At the end of the experiment, colon length and histological changes were assessed. poly(I:C) pre-conditioned UCMSCs significantly ameliorated the clinical and histopathological severity of DSS-induced colitis compared with UCMSCs or LPS pre-conditioned UCMSCs. In contrast, infusion of LPS pre-conditioned UCMSCs significantly increased clinical signs of disease, colon shortening and histological disease index in DSS-induced colitis. These results show that short in vitro TLR3 pre-conditioning with poly(I:C) enhances the therapeutic efficacy of UCMSCs, which is a major breakthrough for developing improved treatments to patients with inflammatory bowel disease. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Genetic deletion of the bacterial sensor NOD2 improves murine Crohn’s disease-like ileitis independent of functional dysbiosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corridoni, D.; Rodriguez-Palacios, A.; Di Stefano, G.

Although genetic polymorphisms in NOD2 (nucleotide-binding oligomerization domain-containing 2) have been associated with the pathogenesis of Crohn’s disease (CD), little is known regarding the role of wild-type (WT) NOD2 in the gut. To date, most murine studies addressing the role of WT Nod2 have been conducted using healthy (ileitis/colitis-free) mouse strains. Here, we evaluated the effects of Nod2 deletion in a murine model of spontaneous ileitis, i.e., the SAMP1Yit/Fc (SAMP) strain, which closely resembles CD. Remarkably, Nod2 deletion improved both chronic cobblestone ileitis (by 50% assessed, as the % of abnormal mucosa at 24 wks of age), as well asmore » acute dextran sodium sulfate (DSS) colitis. Mechanistically, Th2 cytokine production and Th2-transcription factor activation (i.e., STAT6 phosphorylation) were reduced. Microbiologically, the effects of Nod2 deletion appeared independent of fecal microbiota composition and function, assessed by 16S rRNA and metatranscriptomics. Our findings indicate that pharmacological blockade of NOD2 signaling in humans could improve health in Th2-driven chronic intestinal inflammation.« less

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

PubMed

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

2017-12-01

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

A decision support system for prioritizing forested wetland restoration in the Yazoo Backwater Area, Mississippi

USGS Publications Warehouse

O'Hara, Charles G.; Davis, Angela A.; Kleiss, Barbara A.

2000-01-01

A working prototype decision support system (DSS) was developed for the Yazoo Backwater Area, Mississippi, to help planners and managers prioritize, plan, conduct, and optimize forested wetland restoration activities. The DSS comprises geographic information system (GIS) spatial data themes, application programs that provide a cumulative analysis of the relative ability of sites to function as wetlands, and output data that are specific to a given restoration analysis scenario. The DSS input includes GIS data themes such as geomorphology, soils, land use, elevation, farmed wetlands, flood frequency, topographic depressions, streams, public lands, roads, and permanent water bodies, which can be used as spatial templates to define areal hydrologic settings. These GIS data themes can then be ranked and combined to estimate the relative suitability of a potential wetland restoration site, thereby, determining relative wetland equivalence on the landscape. The GIS applications used in this DSS perform the following three functions: assess the ecology (the Eco-Assessor); reclassify land-use in areas selected for restoration (the Tree-Translator); and generate output data to compare restoration scenarios (the Parameter-Generator). Areas selected for reforestation are translated (in the GIS) into ?forested? land use, and the tree species that are ?planted? on the landscape (in the DSS) either compose an ecologically optimal or an economically optimal community of tree species. Output from the DSS can be compared and analyzed by using economic, statistical, graphical, and tabular methods. Output data for seven selected scenarios were generated for the Yazoo Backwater Area and are presented as examples to illustrate the flexibility of the DSS to identify areas that meet restoration objectives.

Repeated Oral Exposure to N ε-Carboxymethyllysine, a Maillard Reaction Product, Alleviates Gut Microbiota Dysbiosis in Colitic Mice.

PubMed

ALJahdali, Nesreen; Gadonna-Widehem, Pascale; Delayre-Orthez, Carine; Marier, David; Garnier, Benjamin; Carbonero, Franck; Anton, Pauline M

2017-12-01

Diet is suggested to participate in the etiology of inflammatory bowel diseases (IBD). Repeated exposure to Maillard reaction products (MRPs), molecules resulting from reduction reactions between amino acids and sugars during food heating, has been reported to be either potentially detrimental or beneficial to health. The aim of this study is to determine the effect of repeated oral ingestion of N ε -carboxymethyllysine (CML), an advanced MRP, on the onset of two models of experimental IBD and on the gut microbiota composition of mice. Mice received either saline (control) or N ε -carboxymethyllysine daily for 21 days. For the last week of treatment, each group was split into subgroups, receiving dextran sulfate sodium salt (DSS) or trinitrobenzenesulfonic acid (TNBS) to induce colitis. Intensity of inflammation was quantified, and cecal microbiota characterized by bacterial 16S ribosomal RNA (rRNA) amplicon sequencing. Daily oral administration of N ε -carboxymethyllysine did not induce intestinal inflammation and had limited impact on gut microbiota composition (Bacteroidaceae increase, Lachnospiraceae decrease). DSS and TNBS administration resulted in expected moderate experimental colitis with a shift of Bacteroidetes/Firmicutes ratio and a significant Proteobacteria increase but with distinct profiles: different Proteobacteria taxa for DSS, but mainly Enterobacteriaceae for TNBS. While N ε -carboxymethyllysine exposure failed to prevent the inflammatory response, it allowed maintenance of healthy gut microbiota profiles in mice treated with DSS (but not TNBS). Repeated oral exposure to CML limits dysbiosis in experimental colitis. IBD patients may modulate their microbiota profile by regulating the level and type of dietary MRP consumption.

Intestinal macrophage/epithelial cell-derived CCL11/eotaxin-1 mediates eosinophil recruitment and function in pediatric ulcerative colitis.

PubMed

Ahrens, Richard; Waddell, Amanda; Seidu, Luqman; Blanchard, Carine; Carey, Rebecca; Forbes, Elizabeth; Lampinen, Maria; Wilson, Tara; Cohen, Elizabeth; Stringer, Keith; Ballard, Edgar; Munitz, Ariel; Xu, Huan; Lee, Nancy; Lee, James J; Rothenberg, Marc E; Denson, Lee; Hogan, Simon P

2008-11-15

Clinical studies have demonstrated a link between the eosinophil-selective chemokines, eotaxins (eotaxin-1/CCL11 and eotaxin-2/CCL24), eosinophils, and the inflammatory bowel diseases, Crohn's disease and ulcerative colitis (UC). However, the cellular source and individual contribution of the eotaxins to colonic eosinophilic accumulation in inflammatory bowel diseases remain unclear. In this study we demonstrate, by gene array and quantitative PCR, elevated levels of eotaxin-1 mRNA in the rectosigmoid colon of pediatric UC patients. We show that elevated levels of eotaxin-1 mRNA positively correlated with rectosigmoid eosinophil numbers. Further, colonic eosinophils appeared to be degranulating, and the levels positively correlated with disease severity. Using the dextran sodium sulfate (DSS)-induced intestinal epithelial injury model, we show that DSS treatment of mice strongly induced colonic eotaxin-1 and eotaxin-2 expression and eosinophil levels. Analysis of eosinophil-deficient mice defined an effector role for eosinophils in disease pathology. DSS treatment of eotaxin-2(-/-) and eotaxin-1/2(-/-) mice demonstrated that eosinophil recruitment was dependent on eotaxin-1. In situ and immunofluorescence analysis-identified eotaxin-1 expression was restricted to intestinal F4/80(+)CD11b(+) macrophages in DSS-induced epithelial injury and to CD68(+) intestinal macrophages and the basolateral compartment of intestinal epithelial cells in pediatric UC. These data demonstrate that intestinal macrophage and epithelial cell-derived eotaxin-1 plays a critical role in the regulation of eosinophil recruitment in colonic eosinophilic disease such as pediatric UC and provides a basis for targeting the eosinophil/eotaxin-1 axis in UC.

Supplementation of the diet with Salecan attenuates the symptoms of colitis induced by dextran sulphate sodium in mice.

PubMed

Zhou, Mengyi; Wang, Zhongqiu; Chen, Jinping; Zhan, Yibei; Wang, Tao; Xia, Lin; Wang, Shiming; Hua, Zichun; Zhang, Jianfa

2014-05-28

As a water-soluble extracellular β-glucan produced by Agrobacterium sp. ZX09, Salecan has an excellent toxicological profile and exerts multiple physiological effects. The aims of the present study were to investigate the protective effects of a Salecan diet in the well-defined dextran sulphate sodium (DSS) model of experimental murine colitis and to elucidate the mechanism involved in its effects with special attention being paid to its effect on the production of TNF-α, a primary mediator involved in the inflammatory response. Male C57BL/6J mice were fed a diet supplemented with either 4 or 8 % Salecan for 26 d and DSS was administered to induce acute colitis during the last 5 d of the experimental period. Several clinical and inflammatory parameters as well as mRNA expression of TNF-α and Dectin-1 were evaluated. The results indicated that the dietary incorporation of Salecan attenuated the severity of DSS colitis as evidenced by the decreased disease activity index, reduced severity of anaemia, attenuated changes in colon architecture and reduced colonic myeloperoxidase activity. This protection was associated with the down-regulation of TNF-α mRNA levels, which might derive from its ability to increase Dectin-1 mRNA levels. In conclusion, the present study suggests that Salecan contributes to the reduction of colonic damage and inflammation in mice with DSS-induced colitis and holds promise as a new, effective nutritional supplement in the management of inflammatory bowel disease.

Enhancement of brain-targeting delivery of danshensu in rat through conjugation with pyrazine moiety to form danshensu-pyrazine ester.

PubMed

Hui, Ailing; Yin, Huayang; Zhang, Zheng; Zhou, An; Chen, Jingchao; Yang, Li; Wu, Zeyu; Zhang, Wencheng

2018-06-01

Tetramethylpyrazine was introduced to the structure of danshensu (DSS) as P-glycoprotein (P-gp)-inhibiting carrier, designing some novel brain-targeting DSS-pyrazine derivatives via prodrug delivery strategy. Following the virtual screening, three DSS-pyrazine esters (DT1, DT2, DT3) were selected because of their better prediction parameters related to brain-targeting. Among them, DT3 was thought to be a promising candidate due to its appropriate bioreversible property in vitro release assay. Further investigation with regard to DT3's brain-targeting effects in vivo was also reported in this study. High-performance liquid chromatography-diode array detection (HPLC-DAD) method was established for the quantitative determination of DT3 and DSS in rat plasma, brain homogenate after intravenous injection. In vivo metabolism of DT3 indicated that it was first converted into DT1, DT2, then the generation of DSS, which could be the result of carboxylesterase activity in rat blood and brain tissue. Moreover, the brain pharmacokinetics of DT3 was significantly altered with 2.16 times increase in half-life compared with that of DSS, and its drug targeting index (DTI) was up to 16.95. Above these data demonstrated that DT3 had better tendency of brain-targeting delivery, which would be positive for the treatment of brain-related disorders.

Simulation of Water Levels and Salinity in the Rivers and Tidal Marshes in the Vicinity of the Savannah National Wildlife Refuge, Coastal South Carolina and Georgia

USGS Publications Warehouse

Conrads, Paul; Roehl, Edwin A.; Daamen, Ruby C.; Kitchens, Wiley M.

2006-01-01

The Savannah Harbor is one of the busiest ports on the East Coast of the United States and is located downstream from the Savannah National Wildlife Refuge, which is one of the Nation?s largest freshwater tidal marshes. The Georgia Ports Authority and the U.S. Army Corps of Engineers funded hydrodynamic and ecological studies to evaluate the potential effects of a proposed deepening of Savannah Harbor as part of the Environmental Impact Statement. These studies included a three-dimensional (3D) model of the Savannah River estuary system, which was developed to simulate changes in water levels and salinity in the system in response to geometry changes as a result of the deepening of Savannah Harbor, and a marsh-succession model that predicts plant distribution in the tidal marshes in response to changes in the water-level and salinity conditions in the marsh. Beginning in May 2001, the U.S. Geological Survey entered into cooperative agreements with the Georgia Ports Authority to develop empirical models to simulate the water level and salinity of the rivers and tidal marshes in the vicinity of the Savannah National Wildlife Refuge and to link the 3D hydrodynamic river-estuary model and the marsh-succession model. For the development of these models, many different databases were created that describe the complexity and behaviors of the estuary. The U.S. Geological Survey has maintained a network of continuous streamflow, water-level, and specific-conductance (field measurement to compute salinity) river gages in the study area since the 1980s and a network of water-level and salinity marsh gages in the study area since 1999. The Georgia Ports Authority collected water-level and salinity data during summer 1997 and 1999 and collected continuous water-level and salinity data in the marsh and connecting tidal creeks from 1999 to 2002. Most of the databases comprise time series that differ by variable type, periods of record, measurement frequency, location, and reliability. Understanding freshwater inflows, tidal water levels, and specific conductance in the rivers and marshes is critical to enhancing the predictive capabilities of a successful marsh succession model. Data-mining techniques, including artificial neural network (ANN) models, were applied to address various needs of the ecology study and to integrate the riverine predictions from the 3D model to the marsh-succession model. ANN models were developed to simulate riverine water levels and specific conductance in the vicinity of the tidal marshes for the full range of historical conditions using data from the river gaging networks. ANN models were also developed to simulate the marsh water levels and pore-water salinities using data from the marsh gaging networks. Using the marsh ANN models, the continuous marsh network was hindcasted to be concurrent with the long-term riverine network. The hindcasted data allow ecologists to compute hydrologic parameters?such as hydroperiods and exposure frequency?to help analyze historical vegetation data. To integrate the 3D hydrodynamic model, the marsh-succession model, and various time-series databases, a decision support system (DSS) was developed to support the various needs of regulatory and scientific stakeholders. The DSS required the development of a spreadsheet application that integrates the database, 3D hydrodynamic model output, and ANN riverine and marsh models into a single package that is easy to use and can be readily disseminated. The DSS allows users to evaluate water-level and salinity response for different hydrologic conditions. Savannah River streamflows can be controlled by the user as constant flow, a percentage of historical flows, a percentile daily flow hydrograph, or as a user-specified hydrograph. The DSS can also use output from the 3D model at stream gages near the Savannah National Wildlife Refuge to simulate the effects in the tidal marshes. The DSS is distributed with a two-dimensional (

Bovine milk-derived α-lactalbumin inhibits colon inflammation and carcinogenesis in azoxymethane and dextran sodium sulfate-treated mice.

PubMed

Yamaguchi, Makoto; Takai, Shoko; Hosono, Akira; Seki, Taiichiro

2014-01-01

Cyclooxygenase-2 is expressed early in colon carcinogenesis and plays crucial role in the progress of the disease. Recently, we found that α-lactalbumin had anti-inflammatory activity by inhibiting cyclooxygenase-2. In experiment 1, we investigated the effects of α-lactalbumin on the colon carcinogenesis initiated with azoxymethane (AOM) followed by promotion with dextran sodium sulfate (DSS) in mice. Dietary treatment with α-lactalbumin decreased fecal occult blood score at 3 days after DSS intake. α-Lactalbumin also decreased the colon tumor at week 9. In experiment 2, AOM-treated mice were sacrificed at 7 days after DSS intake. The plasma and colon prostaglandin E2 (PGE2) levels in AOM/DSS-treated mice were higher than those in the DSS-treated mice without initiation by AOM. α-Lactalbumin decreased PGE2 in both plasma and colon. These results suggest that α-lactalbumin effectively inhibited colon carcinogenesis, and the inhibition may be due to the decreased PGE2 by inhibiting cyclooxygenase-2 at cancer promotion stages.

The Effect of Oral Intake of Low-Temperature-Processed Whey Protein Concentrate on Colitis and Gene Expression Profiles in Mice

PubMed Central

Jayatilake, Sharmila; Arai, Katsuhito; Kumada, Nanami; Ishida, Yoshiko; Tanaka, Ichiro; Iwatsuki, Satoru; Ohwada, Takuji; Ohnishi, Masao; Tokuji, Yoshihiko; Kinoshita, Mikio

2014-01-01

Inflammatory bowel disease (IBD) is an autoimmune disease of unknown etiology and can lead to inflammation and cancer. Whey proteins contain many bioactive peptides with potential health benefits against IBD. We investigated the effect of low-temperature-processed whey protein concentrate (LWPC) on the suppression of IBD by using a dextran sodium sulfate (DSS)-induced colitis model in BALB/c mice. Oral intake of LWPC resulted in improved recovery of body weight in mice. Histological analysis showed that the epithelium cells of LWPC-treated mice were healthier and that lymphocyte infiltration was reduced. The increase in mucin due to the LWPC also reflected reduced inflammation in the colon. Transcriptome analysis of the colon by DNA microarrays revealed marked downregulation of genes related to immune responses in LWPC-fed mice. In particular, the expression of interferon gamma receptor 2 (Ifngr2) and guanylate-binding proteins (GBPs) was increased by DSS treatment and decreased in LWPC-fed mice. These findings suggest that LWPCs suppress DSS-induced inflammation in the colon by suppressing the signaling of these cytokines. Our findings suggest that LWPCs would be an effective food resource for suppressing IBD symptoms. PMID:28234324

The Effect of Oral Intake of Low-Temperature-Processed Whey Protein Concentrate on Colitis and Gene Expression Profiles in Mice.

PubMed

Jayatilake, Sharmila; Arai, Katsuhito; Kumada, Nanami; Ishida, Yoshiko; Tanaka, Ichiro; Iwatsuki, Satoru; Ohwada, Takuji; Ohnishi, Masao; Tokuji, Yoshihiko; Kinoshita, Mikio

2014-06-13

Inflammatory bowel disease (IBD) is an autoimmune disease of unknown etiology and can lead to inflammation and cancer. Whey proteins contain many bioactive peptides with potential health benefits against IBD. We investigated the effect of low-temperature-processed whey protein concentrate (LWPC) on the suppression of IBD by using a dextran sodium sulfate (DSS)-induced colitis model in BALB/c mice. Oral intake of LWPC resulted in improved recovery of body weight in mice. Histological analysis showed that the epithelium cells of LWPC-treated mice were healthier and that lymphocyte infiltration was reduced. The increase in mucin due to the LWPC also reflected reduced inflammation in the colon. Transcriptome analysis of the colon by DNA microarrays revealed marked downregulation of genes related to immune responses in LWPC-fed mice. In particular, the expression of interferon gamma receptor 2 (Ifngr2) and guanylate-binding proteins (GBPs) was increased by DSS treatment and decreased in LWPC-fed mice. These findings suggest that LWPCs suppress DSS-induced inflammation in the colon by suppressing the signaling of these cytokines. Our findings suggest that LWPCs would be an effective food resource for suppressing IBD symptoms.

Software Comparison for Renewable Energy Deployment in a Distribution Network

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, David Wenzhong; Muljadi, Eduard; Tian, Tian

The main objective of this report is to evaluate different software options for performing robust distributed generation (DG) power system modeling. The features and capabilities of four simulation tools, OpenDSS, GridLAB-D, CYMDIST, and PowerWorld Simulator, are compared to analyze their effectiveness in analyzing distribution networks with DG. OpenDSS and GridLAB-D, two open source software, have the capability to simulate networks with fluctuating data values. These packages allow the running of a simulation each time instant by iterating only the main script file. CYMDIST, a commercial software, allows for time-series simulation to study variations on network controls. PowerWorld Simulator, another commercialmore » tool, has a batch mode simulation function through the 'Time Step Simulation' tool, which obtains solutions for a list of specified time points. PowerWorld Simulator is intended for analysis of transmission-level systems, while the other three are designed for distribution systems. CYMDIST and PowerWorld Simulator feature easy-to-use graphical user interfaces (GUIs). OpenDSS and GridLAB-D, on the other hand, are based on command-line programs, which increase the time necessary to become familiar with the software packages.« less

Effects of a computerized cardiac teletriage decision support system on nurse performance: results of a controlled human factors experiment using a mid-fidelity prototype.

PubMed

Somoza, Kirsten Carroll; Momtahan, Kathryn; Lindgaard, Gitte

2007-01-01

A gap exists in cardiac care between known best practices and the actual level of care administered. To help bridge this gap, a proof of concept interface for a PDA-based decision support system (DSS) was designed for cardiac care nurses engaged in teletriage. This interface was developed through a user-centered design process. Quality of assessment, quality of recommendations, and number of questions asked were measured. Cardiac floor nurses' assessment quality performance, but not their recommendation quality performance, improved with the DSS. Nurses asked more questions with the DSS than without it, and these additional questions were predominantly classifiable as essential or beneficial to a good assessment. The average participant satisfaction score with the DSS was above neutral.

32 CFR 321.14 - DSS implementation policies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... to all sources of investigative information, including subjects, during interview, in response to questions that go beyond the required printed and oral notices. Agents shall be guided by DSS Handbook for...

32 CFR 321.14 - DSS implementation policies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... to all sources of investigative information, including subjects, during interview, in response to questions that go beyond the required printed and oral notices. Agents shall be guided by DSS Handbook for...

Soybean and Fish Oil Mixture With Different ω-6/ω-3 Polyunsaturated Fatty Acid Ratios Modulates Dextran Sulfate Sodium-Induced Changes in Small Intestinal Intraepithelial γδT-Lymphocyte Expression in Mice.

PubMed

Pai, Man-Hui; Liu, Jun-Jen; Hou, Yu-Chen; Yeh, Chiu-Li

2016-03-01

This study investigated the effect of different ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratios on dextran sulfate sodium (DSS)-induced changes to small intestinal intraepithelial lymphocyte (IEL) γδT-cell expression. Mice were assigned to 3 control and 3 DSS-treated groups and were maintained on a low-fat semipurified diet. One of the control (S) groups and a DSS (DS) group were provided with soybean oil; the other 2 control (Hω-3 and Lω-3) groups and 2 other DSS (DHω-3 and DLω-3) groups were fed either a soybean and fish oil mixture with a ω-6/ω-3 ratio of 2:1 or 4:1. After feeding the respective diets for 2 weeks, the DSS groups were given distilled water containing 2% DSS, and the control groups were given distilled water for 5 days. All groups were further provided distilled water 5 days for recovery, and the small intestinal IEL γδT-cell subset was isolated for analysis. DSS treatment resulted in a lower small intestinal IEL γδT-cell percentage and higher messenger RNA (mRNA) expressions of Reg IIIγ, keratinocyte growth factor (KGF), and complement 5a receptor (C5aR) by IEL γδT cells. Fish oil administration enhanced the proportion of small intestinal IEL γδT cells. Compared with the DLω-3 group, the DHω-3 group had lower Reg IIIγ, KGF, and C5aR mRNA expressions and higher expression of peroxisome proliferator-activated receptor (PPAR)-γ gene by small intestinal IEL γδT cells. Fish oil diets with a ω-6/ω-3 PUFA ratio of 2:1 were more effective than those with a ratio of 4:1 in improving DSS-induced small intestinal injury, and activation of PPAR-γ in IEL γδT cells may be associated with resolution of small intestinal inflammation. © 2014 American Society for Parenteral and Enteral Nutrition.

Obstructive sleep apnea and neurocognitive function in a Hispanic/Latino population.

PubMed

Ramos, Alberto R; Tarraf, Wassim; Rundek, Tatjana; Redline, Susan; Wohlgemuth, William K; Loredo, Jose S; Sacco, Ralph L; Lee, David J; Arens, Raanan; Lazalde, Patricia; Choca, James P; Mosley, Thomas; González, Hector M

2015-01-27

We evaluated the association between obstructive sleep apnea (OSA) and neurocognitive function among community-dwelling Hispanic/Latino individuals in the United States. Cross-sectional analysis of the Hispanic Community Health Study/Study of Latinos middle-aged and older adults, aged 45 to 74 years, with neurocognitive test scores at baseline measurements from 2008 to 2011. Neurocognitive scores were measured using the Word Fluency (WF) Test, the Brief-Spanish English Verbal Learning Test (SEVLT), and the Digit Symbol Substitution (DSS) Test. OSA was defined by the apnea-hypopnea index (AHI). Multivariable linear regression models were fit to evaluate relations between OSA and neurocognitive scores. The analysis consisted of 8,059 participants, mean age of 56 years, 55% women, and 41% with less than high school education. The mean AHI was 9.0 (range 0-142; normal AHI <5/h). There was an association between the AHI and all 4 neurocognitive test scores: Brief-SEVLT-sum (β = -0.022) and -recall (β = -0.010), WF (β = -0.023), and DSS (β = -0.050) at p < 0.01 that was fully attenuated by age. In the fully adjusted regression model, female sex was a moderating factor between the AHI and WF (β = -0.027, p < 0.10), SVELT-sum (β = -0.37), SVELT-recall (β = -0.010), and DSS (β = -0.061) at p < 0.01. OSA was associated with worse neurocognitive function in a representative sample of Hispanic/Latino women in the United States. © 2014 American Academy of Neurology.

The effects of demand uncertainty on strategic gaming in the merit-order electricity pool market

NASA Astrophysics Data System (ADS)

Frem, Bassam

In a merit-order electricity pool market, generating companies (Gencos) game with their offered incremental cost to meet the electricity demand and earn bigger market shares and higher profits. However when the demand is treated as a random variable instead of as a known constant, these Genco gaming strategies become more complex. After a brief introduction of electricity markets and gaming, the effects of demand uncertainty on strategic gaming are studied in two parts: (1) Demand modelled as a discrete random variable (2) Demand modelled as a continuous random variable. In the first part, we proposed an algorithm, the discrete stochastic strategy (DSS) algorithm that generates a strategic set of offers from the perspective of the Gencos' profits. The DSS offers were tested and compared to the deterministic Nash equilibrium (NE) offers based on the predicted demand. This comparison, based on the expected Genco profits, showed the DSS to be a better strategy in a probabilistic sense than the deterministic NE. In the second part, we presented three gaming strategies: (1) Deterministic NE (2) No-Risk (3) Risk-Taking. The strategies were then tested and their profit performances were compared using two assessment tools: (a) Expected value and standard deviation (b) Inverse cumulative distribution. We concluded that despite yielding higher profit performance under the right conjectures, Risk-Taking strategies are very sensitive to incorrect conjectures on the competitors' gaming decisions. As such, despite its lower profit performance, the No-Risk strategy was deemed preferable.

Electromagnetic non-destructive technique for duplex stainless steel characterization

NASA Astrophysics Data System (ADS)

Rocha, João Vicente; Camerini, Cesar; Pereira, Gabriela

2016-02-01

Duplex stainless steel (DSS) is a two-phase (ferrite and austenite) material, which exhibits an attractive combination of mechanical properties and high corrosion resistance, being commonly employed for equipment of petrochemical plants, refining units and oil & gas platforms. The best properties of DSS are achieved when the phases are in equal proportions. However, exposition to high temperatures (e.g. welding process) may entail undesired consequences, such as deleterious phases precipitation (e.g. sigma, chi) and different proportion of the original phases, impairing dramatically the mechanical and corrosion properties of the material. A detailed study of the magnetic behavior of DSS microstructure with different ferrite austenite ratios and deleterious phases content was accomplished. The non destructive method evaluates the electromagnetic properties changes in the material and is capable to identify the presence of deleterious phases into DSS microstructure.

Nitride alloy layer formation of duplex stainless steel using nitriding process

NASA Astrophysics Data System (ADS)

Maleque, M. A.; Lailatul, P. H.; Fathaen, A. A.; Norinsan, K.; Haider, J.

2018-01-01

Duplex stainless steel (DSS) shows a good corrosion resistance as well as the mechanical properties. However, DSS performance decrease as it works under aggressive environment and at high temperature. At the mentioned environment, the DSS become susceptible to wear failure. Surface modification is the favourable technique to widen the application of duplex stainless steel and improve the wear resistance and its hardness properties. Therefore, the main aim of this work is to nitride alloy layer on the surface of duplex stainless steel by the nitriding process temperature of 400°C and 450°C at different time and ammonia composition using a horizontal tube furnace. The scanning electron microscopy and x-ray diffraction analyzer are used to analyse the morphology, composition and the nitrided alloy layer for treated DSS. The micro hardnesss Vickers tester was used to measure hardness on cross-sectional area of nitrided DSS. After nitriding, it was observed that the hardness performance increased until 1100 Hv0.5kgf compared to substrate material of 250 Hv0.5kgf. The thickness layer of nitride alloy also increased from 5μm until 100μm due to diffusion of nitrogen on the surface of DSS. The x-ray diffraction results showed that the nitride layer consists of iron nitride, expanded austenite and chromium nitride. It can be concluded that nitride alloy layer can be produced via nitriding process using tube furnace with significant improvement of microstructural and hardness properties.

Blockade of AT1 Receptors Protects the Blood–Brain Barrier and Improves Cognition in Dahl Salt-Sensitive Hypertensive Rats

PubMed Central

Pelisch, Nicolas; Hosomi, Naohisa; Ueno, Masaki; Nakano, Daisuke; Hitomi, Hirofumi; Mogi, Masaki; Shimada, Kenji; Kobori, Hiroyuki; Horiuchi, Masatsugu; Sakamoto, Haruhiko; Matsumoto, Masayasu; Kohno, Masakazu; Nishiyama, Akira

2011-01-01

BACKGROUND The present study tested the hypothesis that inappropriate activation of the brain renin–angiotensin system (RAS) contributes to the pathogenesis of blood–brain barrier (BBB) disruption and cognitive impairment during development of salt-dependent hypertension. Effects of an angiotensin II (AngII) type-1 receptor blocker (ARB), at a dose that did not reduce blood pressure, were also examined. METHODS Dahl salt-sensitive (DSS) rats at 6 weeks of age were assigned to three groups: low-salt diet (DSS/L; 0.3% NaCl), high-salt diet (DSS/H; 8% NaCl), and high-salt diet treated with ARB, olmesartan at 1 mg/kg. RESULTS DSS/H rats exhibited hypertension, leakage from brain microvessels in the hippocampus, and impaired cognitive functions, which were associated with increased brain AngII levels, as well as decreased mRNA levels of tight junctions (TJs) and collagen-IV in the hippocampus. In DSS/H rats, olmesartan treatment, at a dose that did not alter blood pressure, restored the cognitive decline, and ameliorated leakage from brain microvessels. Olmesartan also decreased brain AngII levels and restored mRNA expression of TJs and collagen-IV in DSS/H rats. CONCLUSIONS These results suggest that during development of salt-dependent hypertension, activation of the brain RAS contributes to BBB disruption and cognitive impairment. Treatment with an ARB could elicit neuroprotective effects in cognitive disorders by preventing BBB permeability, which is independent of blood pressure changes. PMID:21164491

Treatment with a Novel Chemokine-Binding Protein or Eosinophil Lineage-Ablation Protects Mice from Experimental Colitis

PubMed Central

Vieira, Angélica T.; Fagundes, Caio T.; Alessandri, Ana Leticia; Castor, Marina G.M.; Guabiraba, Rodrigo; Borges, Valdinéria O.; Silveira, Kátia Daniella; Vieira, Erica L.M.; Gonçalves, Juliana L.; Silva, Tarcilia A.; Deruaz, Maud; Proudfoot, Amanda E.I.; Sousa, Lirlândia P.; Teixeira, Mauro M.

2009-01-01

Eosinophils are multifunctional leukocytes implicated in numerous inflammatory diseases. The present study was conducted to clarify the precise role of eosinophils in the development of colitis by using eosinophil-depleted mice and a novel chemokine-binding protein that neutralizes CCL11 action. Colitis was induced by administration of dextran sodium sulfate (DSS) to wild-type and eosinophil-deficient ΔdblGATA-1 mice. Accumulation of eosinophils in the gut of mice given DSS paralleled worsening of clinical score and weight loss. In response to DSS, ΔdblGATA-1 mice showed virtual absence of eosinophil recruitment, amelioration of clinical score, weight loss, and tissue destruction, and no lethality. There was a decrease in CXCL1 and CCL3 production and decreased neutrophil influx in the intestine of ΔdblGATA-1 mice. Transfer of bone marrow cells from wild-type mice reconstituted disease manifestation in DSS-treated ΔdblGATA-1 mice, and levels of CCL11 were increased after DSS treatment and localized to inflammatory cells. Treatment with the chemokine-binding protein evasin-4 at a dose that prevented the function of CCL11 greatly ameliorated clinical score, weight loss, overall tissue destruction, and death rates. In conclusion, the influx of eosinophils is critical for the induction of colitis by DSS. Treatment with a novel chemokine-binding protein decreased eosinophil influx and greatly ameliorated colitis, suggesting that strategies that interfere with the recruitment of eosinophils may be useful as therapy for colitis. PMID:19893035

Chymase Level Is a Predictive Biomarker of Dengue Hemorrhagic Fever in Pediatric and Adult Patients.

PubMed

Tissera, Hasitha; Rathore, Abhay P S; Leong, Wei Yee; Pike, Brian L; Warkentien, Tyler E; Farouk, Farouk S; Syenina, Ayesa; Eong Ooi, Eng; Gubler, Duane J; Wilder-Smith, Annelies; St John, Ashley L

2017-11-27

Most patients with dengue experience mild disease, dengue fever (DF), while few develop the life-threatening diseases dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). No laboratory tests predict DHF or DSS. We evaluated whether the serum chymase level can predict DHF or DSS in adult and pediatric patients and the influence of preexisting conditions (PECs) on chymase levels. Serum chymase levels were measured in patients presenting with undifferentiated fever to hospitals in Colombo District, Sri Lanka. The value of serum the chymase concentration and clinical signs and symptoms as predictors of DHF and/or DSS was evaluated by multivariate analysis. We assessed the influence of age, PECs, and day after fever onset on the robustness of the chymase level as a biomarker for DHF and/or DSS. An elevated chymase level in acute phase blood samples was highly indicative of later diagnosis of DHF or DSS for pediatric and adult patients with dengue. No recorded PECs prevented an increase in the chymase level during DHF. However, certain PECs (obesity and cardiac or lung-associated diseases) resulted in a concomitant increase in chymase levels among adult patients with DHF. These results show that patients with acute dengue who present with high levels of serum chymase consistently are at greater risk of DHF. The chymase level is a robust prognostic biomarker of severe dengue for adult and pediatric patients. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Drug shortages in Israel: regulatory perspectives, challenges and solutions.

PubMed

Schwartzberg, Eyal; Ainbinder, Denize; Vishkauzan, Alla; Gamzu, Ronni

2017-01-01

Pharmaceutical drug shortages (DSs) are a global problem which presents challenges to countries around the world. Shortages of pharmaceutical products may have a direct detrimental impact on public health and patients' wellbeing by causing delayed, or even lack of, treatment. Moreover, DSs may force both patients and caregivers to use unfamiliar drugs, which could lead to medication errors. The objective of our study was to analyze DSs in Israel during the years 2013-2015, assessing their etiology and exploring the steps taken for their mitigation and prevention. The database of the Israeli Ministry of Health (MoH) on drug shortages contains all the DSs recorded in Israel since 2013, detailing the cause of the DS, its duration, steps taken in its' management and the availability of generic or therapeutic alternatives. Selected examples of DSs from the database are described in this paper in order to identify the causes of DSs, the scope of the problem and possible solutions. Additionally, we have reviewed the recent activities performed by European Medicine Agency (EMA) and the American Food and Drug Administration (FDA) in their efforts to minimize this problem. Several factors contributing towards DSs in Israel were identified, including quality problems in both the final drug product and in the raw materials, upgrades and improvements of the manufacturing process required by the MoH, manufacturing by a sole supplier, dramatic price decrease in off-patent medications causing the manufacturer to discontinue the distribution of the product in Israel, just-in-time inventory control, and others. One of the most important steps in managing drug shortages was identified to be early notification of the shortage by the Marketing Authorization Holder (MAH) to the MoH. In 2013, the Israeli MoH updated the regulation on drug shortages instructing MAHs on their obligation of early notification to the MoH. Furthermore, various steps dealing with marketing withdrawal of drugs and temporary drug shortages are being implemented in Israel, such as suspending any further reductions in drug prices below 17 new Israeli shekels, instructing all MAHs to maintain no less than 1 month supply of all registered and non-registered drugs in Israel and allowing an expedited registration pathway for well-established use/grandfather drugs. Drug shortages pose significant public health hazards worldwide. Early notification to the MoH and open dialog with MAHs are essential for managing DSs and mitigating their impact. Despite the efforts carried out by health regulatory authorities worldwide, DSs still pose a significant threat to public health.

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

PubMed

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

2015-12-07

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

New biomarkers for increased intestinal permeability induced by dextran sodium sulphate and fasting in chickens.

PubMed

Gilani, S; Howarth, G S; Kitessa, S M; Tran, C D; Forder, R E A; Hughes, R J

2017-10-01

Increased intestinal permeability (IP) can lead to compromised health in chickens. As there is limited literature on in vivo biomarkers to assess increased IP in chickens, the objective of this study was to identify a reliable biomarker of IP using DSS ingestion and fasting models. Male Ross chickens (n = 48) were reared until day 14 on the floor pen in an animal care facility, randomized into the following groups: control, DSS and fasting (each with n = 16), and then placed in metabolism cages. DSS was administered in drinking water at 0.75% from days 16 to 21, while controls and fasted groups received water. All birds had free access to feed and water except the birds in the fasting group that were denied feed for 19.5 h on day 20. On day 21, all chickens were given two separate oral gavages comprising fluorescein isothiocyanate dextran (FITC-d, 2.2 mg in 1 ml/bird) at time zero and lactulose, mannitol and rhamnose (LMR) sugars (0.25 g L, 0.05 g M and 0.05 g R in 2 ml/bird) at 60 min. Whole blood was collected from the brachial vein in a syringe 90 min post-LMR sugar gavage. Serum FITC-d and plasma LMR sugar concentrations were measured by spectrophotometry and high-performance ion chromatography respectively. Plasma concentrations of intestinal fatty acid binding protein, diamine oxidase, tight junction protein (TJP), d-lactate and faecal α-antitrypsin inhibitor concentration were also analysed by ELISA. FITC-d increased significantly (p < 0.05) after fasting compared with control. L/M and L/R ratios for fasting and L/M ratio for DSS increased compared with control chickens (p < 0.05). TJP in plasma was significantly increased due to fasting but not DSS treatment, compared with controls. Other tests did not indicate changes in IP (p > 0.05). We concluded that FITC-d and LMR sugar tests can be used in chickens to assess changes in IP. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

TRIPLICATE SODIUM IODIDE GAMMA RAY MONITORS FOR THE SMALL COLUMN ION EXCHANGE PROGRAM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Couture, A.

2011-09-20

This technical report contains recommendations from the Analytical Development (AD) organization of the Savannah River National Laboratory (SRNL) for a system of triplicate Sodium Iodide (NaI) detectors to be used to monitor Cesium-137 ({sup 137}Cs) content of the Decontaminated Salt Solution (DSS) output of the Small Column Ion Exchange (SCIX) process. These detectors need to be gain stabilized with respect to temperature shifts since they will be installed on top of Tank 41 at the Savannah River Site (SRS). This will be accomplished using NaI crystals doped with the alpha-emitting isotope, Americium-241({sup 241}Am). Two energy regions of the detector outputmore » will be monitored using single-channel analyzers (SCAs), the {sup 137}Cs full-energy {gamma}-ray peak and the {sup 241}Am alpha peak. The count rate in the gamma peak region will be proportional to the {sup 137}Cs content in the DSS output. The constant rate of alpha decay in the NaI crystal will be monitored and used as feedback to adjust the high voltage supply to the detector in response to temperature variation. An analysis of theoretical {sup 137}Cs breakthrough curves was used to estimate the gamma activity expected in the DSS output during a single iteration of the process. Count rates arising from the DSS and background sources were predicted using Microshield modeling software. The current plan for shielding the detectors within an enclosure with four-inch thick steel walls should allow the detectors to operate with the sensitivity required to perform these measurements. Calibration, testing, and maintenance requirements for the detector system are outlined as well. The purpose of SCIX is to remove and concentrate high-level radioisotopes from SRS salt waste resulting in two waste streams. The concentrated high-level waste containing {sup 137}Cs will be sent to the Defense Waste Processing Facility (DWPF) for vitrification and the low-level DSS will be sent to the Saltstone Production Facility (SPF) to be incorporated into grout.« less

Performance testing of collision-avoidance system for power wheelchairs.

PubMed

Lopresti, Edmund F; Sharma, Vinod; Simpson, Richard C; Mostowy, L Casimir

2011-01-01

The Drive-Safe System (DSS) is a collision-avoidance system for power wheelchairs designed to support people with mobility impairments who also have visual, upper-limb, or cognitive impairments. The DSS uses a distributed approach to provide an add-on, shared-control, navigation-assistance solution. In this project, the DSS was tested for engineering goals such as sensor coverage, maximum safe speed, maximum detection distance, and power consumption while the wheelchair was stationary or driven by an investigator. Results indicate that the DSS provided uniform, reliable sensor coverage around the wheelchair; detected obstacles as small as 3.2 mm at distances of at least 1.6 m; and attained a maximum safe speed of 4.2 km/h. The DSS can drive reliably as close as 15.2 cm from a wall, traverse doorways as narrow as 81.3 cm without interrupting forward movement, and reduce wheelchair battery life by only 3%. These results have implications for a practical system to support safe, independent mobility for veterans who acquire multiple disabilities during Active Duty or later in life. These tests indicate that a system utilizing relatively low cost ultrasound, infrared, and force sensors can effectively detect obstacles in the vicinity of a wheelchair.

Caffeic acid ameliorates colitis in association with increased Akkermansia population in the gut microbiota of mice

PubMed Central

Zhang, Zhan; Wu, Xinyue; Cao, Shuyuan; Wang, Li; Wang, Di; Yang, Hui; Feng, Yiming; Wang, Shoulin; Li, Lei

2016-01-01

Emerging evidence shows that dietary agents and phytochemicals contribute to the prevention and treatment of ulcerative colitis (UC). We first reported the effects of dietary caffeic acid (CaA) on murine experimental colitis and on fecal microbiota. Colitis was induced in C57BL/6 mice by administration of 2.5% dextran sulfate sodium (DSS). Mice were fed a control diet or diet with CaA (1 mM). Our results showed that dietary CaA exerted anti-inflammatory effects in DSS colitis mice. Moreover, CaA could significantly suppress the secretion of IL-6, TNFα, and IFNγ and the colonic infiltration of CD3+ T cells, CD177+ neutrophils and F4/80+ macrophages via inhibition of the activation of NF-κB signaling pathway. Analysis of fecal microbiota showed that CaA could restore the reduction of richness and inhibit the increase of the ratio of Firmicute to Bacteroidetes in DSS colitis mice. And CaA could dramatically increase the proportion of the mucin-degrading bacterium Akkermansia in DSS colitis mice. Thus, CaA could ameliorate colonic pathology and inflammation in DSS colitis mice, and it might be associated with a proportional increase in Akkermansia. PMID:27177331

Speech perception in medico-legal assessment of hearing disabilities.

PubMed

Pedersen, Ellen Raben; Juhl, Peter Møller; Wetke, Randi; Andersen, Ture Dammann

2016-10-01

Examination of Danish data for medico-legal compensations regarding hearing disabilities. The study purposes are: (1) to investigate whether discrimination scores (DSs) relate to patients' subjective experience of their hearing and communication ability (the latter referring to audio-visual perception), (2) to compare DSs from different discrimination tests (auditory/audio-visual perception and without/with noise), and (3) to relate different handicap measures in the scaling used for compensation purposes in Denmark. Data from a 15 year period (1999-2014) were collected and analysed. The data set includes 466 patients, from which 50 were omitted due to suspicion of having exaggerated their hearing disabilities. The DSs relate well to the patients' subjective experience of their speech perception ability. By comparing DSs for different test setups it was found that adding noise entails a relatively more difficult listening condition than removing visual cues. The hearing and communication handicap degrees were found to agree, whereas the measured handicap degrees tended to be higher than the self-assessed handicap degrees. The DSs can be used to assess patients' hearing and communication abilities. The difference in the obtained handicap degrees emphasizes the importance of collecting self-assessed as well as measured handicap degrees.

Development of a model-based flood emergency management system in Yujiang River Basin, South China

NASA Astrophysics Data System (ADS)

Zeng, Yong; Cai, Yanpeng; Jia, Peng; Mao, Jiansu

2014-06-01

Flooding is the most frequent disaster in China. It affects people's lives and properties, causing considerable economic loss. Flood forecast and operation of reservoirs are important in flood emergency management. Although great progress has been achieved in flood forecast and reservoir operation through using computer, network technology, and geographic information system technology in China, the prediction accuracy of models are not satisfactory due to the unavailability of real-time monitoring data. Also, real-time flood control scenario analysis is not effective in many regions and can seldom provide online decision support function. In this research, a decision support system for real-time flood forecasting in Yujiang River Basin, South China (DSS-YRB) is introduced in this paper. This system is based on hydrological and hydraulic mathematical models. The conceptual framework and detailed components of the proposed DSS-YRB is illustrated, which employs real-time rainfall data conversion, model-driven hydrologic forecasting, model calibration, data assimilation methods, and reservoir operational scenario analysis. Multi-tiered architecture offers great flexibility, portability, reusability, and reliability. The applied case study results show the development and application of a decision support system for real-time flood forecasting and operation is beneficial for flood control.

Low Frequency Predictive Skill Despite Structural Instability and Model Error

DTIC Science & Technology

2014-09-30

Majda, based on earlier theoretical work. 1. Dynamic Stochastic Superresolution of sparseley observed turbulent systems M. Branicki (Post doc...of numerical models. Here, we introduce and study a suite of general Dynamic Stochastic Superresolution (DSS) algorithms and show that, by...resolving subgridscale turbulence through Dynamic Stochastic Superresolution utilizing aliased grids is a potential breakthrough for practical online

Application of a participative process for DSS development in soil remediation

NASA Astrophysics Data System (ADS)

José Blanco-Velázquez, Francisco; Muñoz-Vallés, Sara; Anaya-Romero, María

2017-04-01

A wide range of current legislation concerning environmental protection and public health at the national and international level include mandatory actions related to site characterization and the implementation of effective soil remediation measures. The efficiency, in terms of reliability and costs, of this kind of assessment, involves the development and linkage of integrated-harmonized databases, simulating models and specialization tools. So far, no data/knowledge engineering technologies in the academy or market provides the possibility for simulating soil remediation processes for hypothetic spatio-temporal scenarios in a harmonized manner across Europe. In this context, under the framework of RECARE (Preventing and Remediating degradation of Soils in Europe through Land Care) project, we are designing a Decision Support System (DSS) comprising a large database of knowledge including soil, climatic and socio-economic attributes, focused on soil remediation techniques that allows the user to automatically perform a more accurate quantifying of soil pollution, spatial identification of vulnerable zones and formulation of action programs to deal with the particular problem under scenarios of climate and land-use changes. The pilot study area is the Guadiamar valley (SW Spain) where the main threat is soil contamination, after a mine spill occurred on April 1998. About four hm3 of acid waters and two hm3 of mud, rich in heavy metals, were released into the Agrio and Guadiamar rivers affecting more than 4,600 ha of agricultural and pasture land. Consequently, the area was subjected to a large-scale phyto-management project, including the removal of sludge and topsoil, the addition of amendments, and plantation of native shrubs and trees. The objective of this research is to test the feasibility of the DSS concept as well as the likelihood to establish a solid high-potential innovation tool, aligned with the scientific and market strategy and within a European dimension. To this aim, we used a participative process during a workshop carried out in 2016, to validate the tool concept through stakeholder involvement. The target group was composed of representatives from the public administration, academic and private sectors and enabled a transdisciplinary learning process for the DSS implementation. The most interesting and valued issue of the DSS was the capacity to simulate the evolution of physical and chemical characteristics of soil at diverse spatio-temporal scales. On the other hand, it was stated that this approach could be useful to estimate economic criteria, but not to predict socio-cultural patterns. The results obtained from the workshop help to organize the base of knowledge for the DSS according to the main associated users. In the next workshop, further criteria related with the evaluation of ecosystem services predicted by the DSS is being carried out. In addition, a multilingual open source survey is been used to encourage and facilitate wider involvement of stakeholders in other case studies across Europe.

Multi-Sensory Aerosol Data and the NRL NAAPS model for Regulatory Exceptional Event Analysis

NASA Astrophysics Data System (ADS)

Husar, R. B.; Hoijarvi, K.; Westphal, D. L.; Haynes, J.; Omar, A. H.; Frank, N. H.

2013-12-01

Beyond scientific exploration and analysis, multi-sensory observations along with models are finding increasing applications for operational air quality management. EPA's Exceptional Event (EE) Rule allows the exclusion of data strongly influenced by impacts from "exceptional events," such as smoke from wildfires or dust from abnormally high winds. The EE Rule encourages the use of satellite observations and other non-standard data along with models as evidence for formal documentation of EE samples for exclusion. Thus, the implementation of the EE Rule is uniquely suited for the direct application of integrated multi-sensory observations and indirectly through the assimilation into an aerosol simulation model. Here we report the results of a project: NASA and NAAPS Products for Air Quality Decision Making. The project uses of observations from multiple satellite sensors, surface-based aerosol measurements and the NRL Aerosol Analysis and Prediction System (NAAPS) model that assimilates key satellite observations. The satellite sensor data for detecting and documenting smoke and dust events include: MODIS AOD and Images; OMI Aerosol Index, Tropospheric NO2; AIRS, CO. The surface observations include the EPA regulatory PM2.5 network; the IMPROVE/STN aerosol chemical network; AIRNOW PM2.5 mass network, and surface met. data. Within this application, crucial role is assigned to the NAAPS model for estimating the surface concentration of windblown dust and biomass smoke. The operational model assimilates quality-assured daily MODIS data and 2DVAR to adjust the model concentrations and CALIOP-based climatology to adjust the vertical profiles at 6-hour intervals. The assimilation of satellite data from multiple satellites significantly contributes to the usefulness of NAAPS for EE analysis. The NAAPS smoke and dust simulations were evaluated using the IMPROVE/STN chemical data. The multi-sensory observations along with the model simulations are integrated into a web-based Exceptional Event Decision System (EE DSS) application program, designed to support air quality analysts at the Federal and Regional EPA offices and the EE-affected States. EE DSS screening tool automatically identifies the EPA PM2.5 mass samples that are candidates for EE flagging, based mainly on the NAAPS-simulated surface concentration of dust and smoke. The AQ analysts at the States and the EPA can also use the EE DSS to gather further evidence from the examination of spatio-temporal pattern, Absorbing Aerosol Index, CO and NO2 concentration, backward and forward airmass trajectories and other signatures. Since early 2013, the DSS has been used for the identification and analysis of dozens of events. Hence, integration of multi-sensory observations and modeling with data assimilation is maturing to support real-world operational AQ management applications. The remaining challenges can be resolved by seeking ';closure' of the system components; i.e. the systematic adjustments to reconcile the satellite and surface observations, the emissions and their integration through a suitable AQ model.

Intestinal Macrophage/Epithelial Cell-Derived CCL11/Eotaxin-1 Mediates Eosinophil Recruitment and Function in Pediatric Ulcerative Colitis1

PubMed Central

Ahrens, Richard; Waddell, Amanda; Seidu, Luqman; Blanchard, Carine; Carey, Rebecca; Forbes, Elizabeth; Lampinen, Maria; Wilson, Tara; Cohen, Elizabeth; Stringer, Keith; Ballard, Edgar; Munitz, Ariel; Xu, Huan; Lee, Nancy; Lee, James J.; Rothenberg, Marc E.; Denson, Lee; Hogan, Simon P.

2009-01-01

Clinical studies have demonstrated a link between the eosinophil-selective chemokines, eotaxins (eotaxin-1/CCL11 and eotaxin-2/CCL24), eosinophils, and the inflammatory bowel diseases, Crohn’s disease and ulcerative colitis (UC). However, the cellular source and individual contribution of the eotaxins to colonic eosinophilic accumulation in inflammatory bowel diseases remain unclear. In this study we demonstrate, by gene array and quantitative PCR, elevated levels of eotaxin-1 mRNA in the rectosigmoid colon of pediatric UC patients. We show that elevated levels of eotaxin-1 mRNA positively correlated with rectosigmoid eosinophil numbers. Further, colonic eosinophils appeared to be degranulating, and the levels positively correlated with disease severity. Using the dextran sodium sulfate (DSS)-induced intestinal epithelial injury model, we show that DSS treatment of mice strongly induced colonic eotaxin-1 and eotaxin-2 expression and eosinophil levels. Analysis of eosinophil-deficient mice defined an effector role for eosinophils in disease pathology. DSS treatment of eotaxin-2−/− and eotaxin-1/2−/− mice demonstrated that eosinophil recruitment was dependent on eotaxin-1. In situ and immunofluorescence analysis-identified eotaxin-1 expression was restricted to intestinal F4/80+CD11b+ macrophages in DSS-induced epithelial injury and to CD68+ intestinal macrophages and the basolateral compartment of intestinal epithelial cells in pediatric UC. These data demonstrate that intestinal macrophage and epithelial cell-derived eotaxin-1 plays a critical role in the regulation of eosinophil recruitment in colonic eosinophilic disease such as pediatric UC and provides a basis for targeting the eosinophil/eotaxin-1 axis in UC. PMID:18981162

In vitro reconstitution and characterization of the yeast mitochondrial degradosome complex unravels tight functional interdependence.

PubMed

Malecki, Michal; Jedrzejczak, Robert; Stepien, Piotr P; Golik, Pawel

2007-09-07

The mitochondrial degradosome (mtEXO), the main RNA-degrading complex of yeast mitochondria, is composed of two subunits: an exoribonuclease encoded by the DSS1 gene and an RNA helicase encoded by the SUV3 gene. We expressed both subunits of the yeast mitochondrial degradosome in Escherichia coli, reconstituted the complex in vitro and analyzed the RNase, ATPase and helicase activities of the two subunits separately and in complex. The results reveal a very strong functional interdependence. For every enzymatic activity, we observed significant changes when the relevant protein was present in the complex, compared to the activity measured for the protein alone. The ATPase activity of Suv3p is stimulated by RNA and its background activity in the absence of RNA is reduced greatly when the protein is in the complex with Dss1p. The Suv3 protein alone does not display RNA-unwinding activity and the 3' to 5' directional helicase activity requiring a free 3' single-stranded substrate becomes apparent only when Suv3p is in complex with Dss1p. The Dss1 protein alone does have some basal exoribonuclease activity, which is not ATP-dependent, but in the presence of Suv3p the activity of the entire complex is enhanced greatly and is entirely ATP-dependent, with no residual activity observed in the absence of ATP. Such absolute ATP-dependence is unique among known exoribonuclease complexes. On the basis of these results, we propose a model in which the Suv3p RNA helicase acts as a molecular motor feeding the substrate to the catalytic centre of the RNase subunit.

Analysing the effect of I1 imidazoline receptor ligands on DSS-induced acute colitis in mice.

PubMed

Fehér, Ágnes; Tóth, Viktória E; Al-Khrasani, Mahmoud; Balogh, Mihály; Lázár, Bernadette; Helyes, Zsuzsanna; Gyires, Klára; Zádori, Zoltán S

2017-02-01

Imidazoline receptors (IRs) have been recognized as promising targets in the treatment of numerous diseases; and moxonidine and rilmenidine, agonists of I 1 -IRs, are widely used as antihypertensive agents. Some evidence suggests that IR ligands may induce anti-inflammatory effects acting on I 1 -IRs or other molecular targets, which could be beneficial in patients with inflammatory bowel disease (IBD). On the other hand, several IR ligands may stimulate also alpha 2 -adrenoceptors, which were earlier shown to inhibit, but in more recent studies to rather aggravate colitis. Hence, this study aimed to analyse for the first time the effect of various I 1 -IR ligands on intestinal inflammation. Colitis was induced in C57BL/6 mice by adding dextran sulphate sodium (DSS) to the drinking water for 7 days. Mice were treated daily with different IR ligands: moxonidine and rilmenidine (I 1 -IR agonists), AGN 192403 (highly selective I 1 -IR ligand, putative antagonist), efaroxan (I 1 -IR antagonist), as well as with the endogenous IR agonists agmatine and harmane. It was found that moxonidine and rilmenidine at clinically relevant doses, similarly to the other IR ligands, do not have a significant impact on the macroscopic and histological signs of DSS-evoked inflammation. Likewise, colonic myeloperoxidase and serum interleukin-6 levels remained unchanged in response to these agents. Thus, our study demonstrates that imidazoline ligands do not influence significantly the severity of DSS-colitis in mice and suggest that they probably neither affect the course of IBD in humans. However, the translational value of these findings needs to be verified with other experimental colitis models and human studies.

The enhanced susceptibility of ADAM-17 hypomorphic mice to DSS-induced colitis is not ameliorated by loss of RIPK3, revealing an unexpected function of ADAM-17 in necroptosis

PubMed Central

Luzius, Anne; Saggau, Carina; Ruder, Barbara; Bolik, Julia; Schmidt-Arras, Dirk; Linkermann, Andreas; Becker, Christoph; Rosenstiel, Philip; Rose-John, Stefan; Adam, Dieter

2018-01-01

The disintegrin metalloprotease ADAM17 has a critical role in intestinal inflammation and regeneration in mice, as illustrated by the dramatically increased susceptibility of ADAM17 hypomorphic (ADAM17ex/ex) mice to dextran sulfate sodium (DSS)-induced colitis. Similarly, necroptosis has been implicated in inflammatory responses in the intestine. In this study, we have investigated the contribution of necroptosis to ADAM17-regulated intestinal inflammation in vivo by crossing ADAM17ex/ex mice with mice that lack the necroptotic core protein RIPK3. Despite the loss of RIPK3, ADAM17ex/ex/RIPK3−/− mice showed the same increased susceptibility as ADAM17ex/ex mice in both acute and chronic models of DSS-induced colitis. Mice of both genotypes revealed comparable results with regard to weight loss, disease activity index and colitis-associated changes of inner organs. Histopathological analyses confirmed similar tissue destruction, loss of barrier integrity, immune cell infiltration, and cell death; serum analyses revealed similar levels of the pro-inflammatory cytokine KC. Resolving these unexpected findings, ADAM17ex/ex mice did not show phosphorylation of RIPK3 and its necroptotic interaction partner MLKL during DSS-induced colitis, although both proteins were clearly expressed. Consistent with these findings, murine embryonic fibroblasts derived from ADAM17ex/ex mice were protected from tumor necrosis factor (TNF)-induced necroptosis and failed to show phosphorylation of MLKL and RIPK3 after induction of necroptosis by TNF, revealing a novel, undescribed role of the protease ADAM17 in necroptosis. PMID:29560122

The enhanced susceptibility of ADAM-17 hypomorphic mice to DSS-induced colitis is not ameliorated by loss of RIPK3, revealing an unexpected function of ADAM-17 in necroptosis.

PubMed

Fuchslocher Chico, Johaiber; Falk-Paulsen, Maren; Luzius, Anne; Saggau, Carina; Ruder, Barbara; Bolik, Julia; Schmidt-Arras, Dirk; Linkermann, Andreas; Becker, Christoph; Rosenstiel, Philip; Rose-John, Stefan; Adam, Dieter

2018-02-27

The disintegrin metalloprotease ADAM17 has a critical role in intestinal inflammation and regeneration in mice, as illustrated by the dramatically increased susceptibility of ADAM17 hypomorphic (ADAM17 ex/ex ) mice to dextran sulfate sodium (DSS)-induced colitis. Similarly, necroptosis has been implicated in inflammatory responses in the intestine. In this study, we have investigated the contribution of necroptosis to ADAM17-regulated intestinal inflammation in vivo by crossing ADAM17 ex/ex mice with mice that lack the necroptotic core protein RIPK3. Despite the loss of RIPK3, ADAM17 ex/ex /RIPK3 -/- mice showed the same increased susceptibility as ADAM17 ex/ex mice in both acute and chronic models of DSS-induced colitis. Mice of both genotypes revealed comparable results with regard to weight loss, disease activity index and colitis-associated changes of inner organs. Histopathological analyses confirmed similar tissue destruction, loss of barrier integrity, immune cell infiltration, and cell death; serum analyses revealed similar levels of the pro-inflammatory cytokine KC. Resolving these unexpected findings, ADAM17 ex/ex mice did not show phosphorylation of RIPK3 and its necroptotic interaction partner MLKL during DSS-induced colitis, although both proteins were clearly expressed. Consistent with these findings, murine embryonic fibroblasts derived from ADAM17 ex/ex mice were protected from tumor necrosis factor (TNF)-induced necroptosis and failed to show phosphorylation of MLKL and RIPK3 after induction of necroptosis by TNF, revealing a novel, undescribed role of the protease ADAM17 in necroptosis.

Exploring the ameliorative potential of probiotic Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum on dextran sodium sulphate induced colitis in mice.

PubMed

Jadhav, Sagar R; Shandilya, Umesh Kr; Kansal, Vinod K

2013-02-01

Conventional medical therapies for ulcerative colitis (UC) are still limited due to the adverse side effects like dose-dependent diarrhoea and insufficient potency to keep in remission for long-term periods. So, new alternatives that provide more effective and safe therapies for ulcerative colitis are constantly being sought. In the present study, probiotic LaBb Dahi was selected for investigation of its therapeutic effect on DSS-induced colitis model in mice. LaBb Dahi was prepared by co-culturing Dahi culture of Lactococci along with selected strain of Lactobacillus acidophilus LaVK2 and Bifidobacterium bifidum BbVK3 in buffalo milk. Four groups of mice (12 each) were fed for 17 d with buffalo milk (normal control), buffalo milk plus DSS (Colitis control), Dahi plus DSS, and LaBb Dahi plus DSS, respectively, with basal diet. The disease activity scores, weight loss, organ weight, colon length, myeloperoxidase (MPO) and β-glucoronidase activity was assessed, and the histopathological picture of the colon of mice was studied. All colitis control mice evidenced significant increase in MPO, β-glucoronidase activity and showed high disease activity scores along with histological damage to colonic tissue. Feeding with LaBb Dahi offered significant reduction in MPO activity, β-glucoronidase activity and improved disease activity scores. We found significant decline in length of colon, organ weight and body weight in colitis induced controls which were improved significantly by feeding LaBb Dahi. The present study suggests that LaBb Dahi can be used as a potential nutraceutical intervention to combat UC related changes and may offer effective adjunctive treatment for management of UC.

The 26-meter antenna s-x conversion project. [Deep Space Network

NASA Technical Reports Server (NTRS)

1982-01-01

Programmatic and management aspects of converting an existing 26-meter S-band subnet to a 34-meter S- and X-band subnet of the Deep Space Network are described. The stations involved were DSS 12 near Barstow, DSS 44 in Australia, and DSS 62 in Spain. The main subsystems affected by the conversion were the antenna mechanical, antenna microwave, and receiver-exciter. Antenna mechanial modifications and electronic additions and changes are described. The design and analysis of critical areas are considered and antenna performance is discussed.

Celastrol Ameliorates Ulcerative Colitis-Related Colorectal Cancer in Mice via Suppressing Inflammatory Responses and Epithelial-Mesenchymal Transition

PubMed Central

Lin, Lianjie; Sun, Yan; Wang, Dongxu; Zheng, Shihang; Zhang, Jing; Zheng, Changqing

2016-01-01

Celastrol, also named as tripterine, is a pharmacologically active ingredient extracted from the root of traditional Chinese herb Tripterygium wilfordii Hook F with potent anti-inflammatory and anti-tumor activities. In the present study, we investigated the effects of celastrol on ulcerative colitis-related colorectal cancer (UC-CRC) as well as CRC in vivo and in vitro and explored its underlying mechanisms. UC-CRC model was induced in C57BL/6 mice by administration of azoxymethane (AOM) and dextran sodium sulfate (DSS). Colonic tumor xenograft models were developed in BALB/c-nu mice by subcutaneous injection with HCT116 and HT-29 cells. Intragastric administration of celastrol (2 mg/kg/d) for 14 weeks significantly increased the survival ratio and reduced the multiplicity of colonic neoplasms compared with AOM/DSS model mice. Mechanically, celastrol treatment significantly prevented AOM/DSS-induced up-regulation of expression levels of oncologic markers including mutated p53 and phospho-p53, β-catenin and proliferating cell nuclear antigen (PCNA). In addition, treatment with celastrol inhibited inflammatory responses, as indicated by the decrease of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, down-regulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), and inactivation of nuclear factor κB (NF-κB). Moreover, celastrol obviously suppressed epithelial-mesenchymal transition (EMT) through up-regulating E-cadherin and down-regulating N-cadherin, Vimentin and Snail. Additionally, we also demonstrated that celastrol inhibited human CRC cell proliferation and attenuated colonic xenograft tumor growth via reversing EMT. Taken together, celastrol could effectively ameliorate UC-CRC by suppressing inflammatory responses and EMT, suggesting a potential drug candidate for UC-CRC therapy. PMID:26793111

Tanshinone IIA ameliorates dextran sulfate sodium-induced inflammatory bowel disease via the pregnane X receptor

PubMed Central

Zhang, Xianxie; Wang, Yuguang; Ma, Zengchun; Liang, Qiande; Tang, Xianglin; Hu, Donghua; Tan, Hongling; Xiao, Chengrong; Gao, Yue

2015-01-01

Tanshinone IIA (Tan IIA) (C19H18O3) is one of the major active lipophilic components in a conventional Chinese medicine called danshen, and it has long been used in the People’s Republic of China and other neighboring countries to treat patients suffering from inflammatory bowel disease (IBD). Previous experiments by many teams determined which mechanism of Tan IIA is relevant to the treatment of IBD associated with inflammation and the pregnane X receptor (PXR). The current study demonstrated that Tan IIA is an efficacious PXR agonist and its ability to induce CYP3A4 mRNA and protein expression was mediated by the transactivation of PXR, a known target of abrogating inflammation in IBD. Clinical symptoms in mice and histological assessment data suggested that administration of Tan IIA in mice demonstrated significant protection and showed that in DSS-induced IBD it acts in a concentration-dependent manner. PXR-silenced mice treated with Tan IIA demonstrated low protection against DSS-induced mouse IBD and exacerbated the severity of IBD compared with wild-type mice; PXR-silenced mice demonstrated the necessity for PXR in Tan IIA-mediated upregulation of xenobiotic metabolism genes. The IBD treatment effects of Tan IIA are partially due to PXR-mediated upregulation of xenobiotic metabolism and downregulation of inflammatory mediators. The novel findings reported here may contribute to the effective utilization of Tan IIA and its derivatives as a PXR ligand in the treatment of human IBD. This suggests that Tan IIA may have considerable clinical utility. PMID:26674743

Açaí Berries Inhibit Colon Tumorigenesis in Azoxymethane/Dextran Sulfate Sodium-Treated Mice

PubMed Central

Choi, Yoon Jin; Choi, Yoon Jeong; Kim, Nayoung; Nam, Ryoung Hee; Lee, Seonmin; Lee, Hye Seung; Lee, Ha-Na; Surh, Young-Joon; Lee, Dong Ho

2017-01-01

Background/Aims The aim of this study was to investigate the protective effect of açaí against azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colorectal cancer development. Methods The effect of açaí on tumorigenesis was assessed by evaluating tumor incidence, multiplicity and invasiveness in the mouse colon. The levels of myeloperoxidase (MPO) and proinflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, and IL-6) were measured via enzyme-linked immunosorbent assay. Protein levels of cyclooxygenase 2 (COX-2), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad) and cleaved-caspase-3 were assessed by immunoblotting. Results Administration of pellets containing 5% açaí powder reduced the incidences of both colonic adenoma and cancer (adenoma, 23.1% vs 76.9%, respectively, p=0.006; cancer, 15.4% vs 76.9%, respectively, p=0.002). In the açaí-treated mice, the MPO, TNF-α, IL-1β and IL-6 levels in the colon were significantly down-regulated. Açaí inhibited PCNA and Bcl-2 expression and increased Bad and cleaved-caspase-3 expression. In vitro studies demonstrated that açaí treatment reduced lipopolysaccharide-induced expression of TNF-α, IL-1β, IL-6 and COX-2 in murine macrophage RAW 264.7 cells. Conclusions Açaí demonstrated protective effects against AOM/DSS-induced colon carcinogenesis, which suggests that the intake of açaí may be beneficial for the prevention of human colon cancer. PMID:27965474

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

PubMed Central

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

2014-01-01

Patients suffering from Inflammatory Bowel Disease (IBD) are currently treated by systemic drugs that can have significant side effects. Thus, it would be highly desirable to target TNFα siRNA (a therapeutic molecule) to the inflamed tissue. Here, we demonstrate that TNFα siRNA can be efficiently loaded into nanoparticles (NPs) made of poly (lactic acid) poly (ethylene glycol) block copolymer (PLA-PEG), and that grafting of the Fab’ portion of the F4/80 Ab (Fab’-bearing) onto the NP surface via maleimide/thiol group-mediated covalent bonding improves the macrophage (MP)-targeting kinetics of the NPs to RAW264.7 cells in vitro. Direct binding was shown between MPs and the Fab’-bearing NPs. Next, we orally administered hydrogel (chitosan/alginate)-encapsulated Fab’-bearing TNFα-siRNA-loaded NPs to 3% dextran sodium sulfate (DSS)-treated mice and investigated the therapeutic effect on colitis. In vivo, the release of TNFα-siRNA-loaded NPs into the mouse colon attenuated colitis more efficiently when the NPs were covered with Fab’-bearing, compared to uncovered NPs. All DSS-induced parameters of colonic inflammation (e.g., weight loss, myeloperoxidase activity, and Iκbα accumulation) were more attenuated Fab’-bearing NPs loaded with TNFα siRNA than without the Fab’-bearing. Grafting the Fab’-bearing onto the NPs improved the kinetics of endocytosis as well as the MP-targeting ability, as indicated by flow cytometry. Collectively, our results show that Fab’-bearing PLA-PEG NPs are powerful and efficient nanosized tools for delivering siRNAs into colonic macrophages. PMID:24810114

Double sac sign and intradecidual sign in early pregnancy: interobserver reliability and frequency of occurrence.

PubMed

Doubilet, Peter M; Benson, Carol B

2013-07-01

To assess the interobserver agreement, frequency of occurrence, and prognostic importance of the double sac sign (DSS), intradecidual sign (IDS), and other sonographic findings in early intrauterine pregnancies. We retrospectively identified all sonograms obtained between January 1, 2006, and December 31, 2011, in which: (1) the scan demonstrated an intrauterine fluid collection without a yolk sac or embryo; (2) a follow-up scan confirmed an intrauterine pregnancy; and (3) the first-trimester outcome was known. Each coinvestigator characterized the 199 study sonograms as demonstrating or not demonstrating a DSS or an IDS, based on judgment about whether the scan met published criteria defining these signs. Interobserver agreement was poor for the DSS (κ= 0.24) and IDS (κ= 0.23). Scans frequently demonstrated neither sign: 150 cases (75.4%) if we considered a sign to be present when both investigators graded it as present and 69 cases (34.7%) using the looser criterion that either graded it as present. The presence of a DSS or an IDS was unrelated to the β-human chorionic gonadotropin (β-hCG) value (P > .05, t test, all comparisons). An inner echogenic ring was present in 158 cases (79.4%), and the decidua was brighter peripherally than centrally in 102 (51.3%). The first-trimester outcome was unrelated to the presence of a DSS or an IDS, presence of an inner echogenic ring, or decidual appearance (P > .05, χ(2), all comparisons). The sonographic appearance of early gestational sacs, before visualization of a yolk sac or embryo, is highly variable. The DSS and IDS are often absent; there is poor interobserver agreement regarding these signs; and the prognosis is unrelated to their presence or absence. A round or oval intrauterine fluid collection in a woman with positive β-hCG should be treated as a gestational sac until proven otherwise, regardless of whether it demonstrates a DSS or an IDS.

Effect of heat treatment on corrosion behavior of duplex stainless steel in orthodontic applications

NASA Astrophysics Data System (ADS)

Sabea Hammood, Ali; Faraj Noor, Ahmed; Talib Alkhafagy, Mohammed

2017-12-01

Heat treatment is necessary for duplex stainless steel (DSS) to remove or dissolve intermetallic phases, to remove segregation and to relieve any residual thermal stress in DSS, which may be formed during production processes. In the present study, the corrosion resistance of a DSS in artificial saliva was studied by potentiodynamic measurements. The microstructure was investigated by scanning electron microscopy (SEM),x-ray diffraction (XRD) and Vickers hardness (HV). The properties were tested in as-received and in thermally treated conditions (800-900 °C, 2-8 min). The research aims to evaluate the capability of DSS for orthodontic applications, in order to substitute the austenitic grades. The results indicate that the corrosion resistance is mainly affected by the ferrite/austenite ratio. The best result was obtained with a treatment at 900 °C for 2 min.

Inter-Satellite Communications Considerations and Requirements for Distributed Spacecraft and Formation Flying Systems

NASA Technical Reports Server (NTRS)

Kwadrat, Carl F.; Horne, William D.; Edwards, Bernard L.

2002-01-01

In order to avoid selecting inadequate inter-spacecraft cross-link communications standards for Distributed Spacecraft System (DSS) missions, it is first necessary to identify cross-link communications strategies and requirements common to a cross-section of proposed missions. This paper addresses the cross-link communication strategies and requirements derived from a survey of 39 DSS mission descriptions that are projected for potential launch within the next 20 years. The inter-spacecraft communications strategies presented are derived from the topological and communications constraints from the DSS missions surveyed. Basic functional requirements are derived from an analysis of the fundamental activities that must be undertaken to establish and maintain a cross-link between two DSS spacecraft. Cross-link bandwidth requirements are derived from high-level assessments of mission science objectives and operations concepts. Finally, a preliminary assessment of possible cross-link standards is presented within the context of the basic operational and interoperability requirements.

Mariner 9 data storage subsystem flight performance summary

NASA Technical Reports Server (NTRS)

Thomas, N. E.; Larman, B. T.

1973-01-01

The performance is summarized of the Mariner 9 Data Storage Subsystem (DSS) throughout the primary and extended missions. Information presented is limited to reporting of anomalies which occurred during the playback sequences. Tables and figures describe the anomalies (dropouts, missing and added bits, in the imaging data) as a function of time (accumulated tape passes). The data results indicate that the performance of the DSS was satisfactory and within specification throughout the mission. The data presented is taken from the Spacecraft Team Incident/Surprise Anomaly Log recorded during the mission. Pertinent statistics concerning the tape transport performance are given. Also presented is a brief description of DSS operation, particularly that related to the recorded anomalies. This covers the video data encoding and how it is interpreted/decoded by ground data processing and the functional operation of the DSS in abnormal conditions such as loss of lock to the playback signal.

An OSI architecture for the deep space network

NASA Technical Reports Server (NTRS)

Heuser, W. Randy; Cooper, Lynne P.

1993-01-01

The flexibility and robustness of a monitor and control system are a direct result of the underlying inter-processor communications architecture. A new architecture for monitor & Control at the Deep Space Network Communications Complexes has been developed based on the Open System Interconnection (OSI) standards. The suitability of OSI standards for DSN M&C has been proven in the laboratory. The laboratory success has resulted in choosing an OSI-based architecture for DSS-13 M&C. DSS-13 is the DSN experimental station and is not part of the 'operational' DSN; it's role is to provide an environment to test new communications concepts can be tested and conduct unique science experiments. Therefore, DSS-13 must be robust enough to support operational activities, while also being flexible enough to enable experimentation. This paper describes the M&C architecture developed for DSS-13 and the results from system and operational testing.

[Effects-of combined calories restriction and polyunsaturated fatty acids on colitis in rats].

PubMed

Qian, Yan; Zhang, Ying; Liu, Hui; Wang, Lei; Li, Xiuhua; Qiu, Fubin

2014-09-01

To explore the effect of n-6 and n-3 polyunsaturated fatty acids combined with calorie restriction( CR) in DSS induced ulcerative colitis rats. Forty female rats were randomly divided into five groups, control group, model group, CR group, 5:1 PUFA ad libitum group, 5: 1 PUFA CR group. CR groups provided with a limited daily food allotment of 60% of that eaten by the ad libitum animals for 14 weeks. Ulcerative colitis model in rats were given 5. 0% dextran sulfate sodium in their drinking water for 7 days. 5:1 PUFA CR group significantly decreased body weight, disease activity index, macroscopic and histological score compared to model group. In addition, administration of 5: 1 PUFA CR effectively inhibited MPO activity. The levels of TNF-α and IL-6 in the serum with colitis were decreased by 5: 1 PUFA CR (P <0. 05). These results suggest that combination of calories restriction and n-6/n-3 =5:1 PUFA may be more beneficial in attenuating the progression of DSS induced ulcerative colitis.

Microbiota transplantation reveals beneficial impact of berberine on hepatotoxicity by improving gut homeostasis.

PubMed

Qin, Chenjie; Zhang, Huilu; Zhao, Linghao; Zeng, Min; Huang, Weijian; Fu, Gongbo; Zhou, Weiping; Wang, Hongyang; Yan, Hexin

2017-11-29

Berberine has been shown to reduce acute liver injury although the underlying mechanism is not fully understood. Because of the anatomic connection, the liver is constantly exposed to gut-derived bacterial products and metabolites. In this study, we showed that berberine has beneficial effects on both hepatotoxicity and intestinal damage in a rat model of chronic or acute liver injury. Microbiota transplantation from the rats with chronic hepatotoxicity could aggravate acute hepatotoxicity in mice treated with diethylnitrosamine (DEN). In rat models with gut homeostasis disruption induced by penicillin or dextran sulfate sodium (DSS), their fecal microbiota could also cause an enhanced hepatotoxicity of recipient mice. When treated with berberine, the DSS-induced enteric dysbacteriosis could be mitigated and their fecal bacteria were able to reduce acute hepatotoxicity in recipient mice. This study indicates that berberine could improve intestinal dysbacteriosis, which reduces the hepatotoxicity caused by pathological or pharmacological intervention. Fecal microbiota transplantation might be a useful method to directly explore homeostatic alteration in gut microbiota.

Pattern-recognition techniques applied to performance monitoring of the DSS 13 34-meter antenna control assembly

NASA Technical Reports Server (NTRS)

Mellstrom, J. A.; Smyth, P.

1991-01-01

The results of applying pattern recognition techniques to diagnose fault conditions in the pointing system of one of the Deep Space network's large antennas, the DSS 13 34-meter structure, are discussed. A previous article described an experiment whereby a neural network technique was used to identify fault classes by using data obtained from a simulation model of the Deep Space Network (DSN) 70-meter antenna system. Described here is the extension of these classification techniques to the analysis of real data from the field. The general architecture and philosophy of an autonomous monitoring paradigm is described and classification results are discussed and analyzed in this context. Key features of this approach include a probabilistic time-varying context model, the effective integration of signal processing and system identification techniques with pattern recognition algorithms, and the ability to calibrate the system given limited amounts of training data. Reported here are recognition accuracies in the 97 to 98 percent range for the particular fault classes included in the experiments.

The Chemical Shift Baseline for High-Pressure NMR Spectra of Proteins.

PubMed

Frach, Roland; Kibies, Patrick; Böttcher, Saraphina; Pongratz, Tim; Strohfeldt, Steven; Kurrmann, Simon; Koehler, Joerg; Hofmann, Martin; Kremer, Werner; Kalbitzer, Hans Robert; Reiser, Oliver; Horinek, Dominik; Kast, Stefan M

2016-07-18

High-pressure (HP) NMR spectroscopy is an important method for detecting rare functional states of proteins by analyzing the pressure response of chemical shifts. However, for the analysis of the shifts it is mandatory to understand the origin of the observed pressure dependence. Here we present experimental HP NMR data on the (15) N-enriched peptide bond model, N-methylacetamide (NMA), in water, combined with quantum-chemical computations of the magnetic parameters using a pressure-sensitive solvation model. Theoretical analysis of NMA and the experimentally used internal reference standard 4,4-dimethyl-4-silapentane-1-sulfonic (DSS) reveal that a substantial part of observed shifts can be attributed to purely solvent-induced electronic polarization of the backbone. DSS is only marginally responsive to pressure changes and is therefore a reliable sensor for variations in the local magnetic field caused by pressure-induced changes of the magnetic susceptibility of the solvent. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identifying uncontrolled asthma in young children: clinical scores or objective variables?

PubMed

Leung, T F; Ko, F W S; Sy, H Y; Wong, E; Li, C Y; Yung, E; Hui, D S C; Wong, G W K; Lai, C K W

2009-03-01

Several international asthma guidelines emphasize the importance of assessing asthma control. However, there is limited data on the usefulness of available assessment tools in indicating disease control in young asthmatics. This study investigated the ability of Chinese version of Childhood Asthma Control Test (C-ACT) and other disease-related factors in identifying uncontrolled asthma (UA) in young children. During the same clinic visit, asthma patients 4 to 11 years of age completed C-ACT and underwent exhaled nitric oxide and spirometric measurements. Blinded to these results, the same investigator assigned Disease Severity Score (DSS) and rated asthma control according to Global Initiative for Asthma. The mean (SD) age of 113 recruited patients was 9.1 (2.0) years, and 35% of them had UA. C-ACT, DSS and forced expiratory volume in 1 second (FEV(1)) differed among patients with different control status (p < 0.001 for C-ACT and DSS; p = 0.014 for FEV(1)). Logistic regression confirmed that UA was associated with DSS (p < 0.001), PEF (p = 0.002), C-ACT (p = 0.011), and FEV(1) (p = 0.012). By ROC analysis, C-ACT and DSS were the best predictors for UA (p < 0.001), followed by PEF (p = 0.006) and FEV(1) (p = 0.007). When analyzed by the Classification and Regression Tree (CART) approach, the sequential use of DSS and C-ACT had 77% sensitivity and 84% specificity in identifying UA. C-ACT is better than objective parameters in identifying young Chinese children with UA.

Mortality and health among internally displaced persons in western Kenya following post-election violence, 2008: novel use of demographic surveillance.

PubMed

Feikin, Daniel R; Adazu, Kubaje; Obor, David; Ogwang, Sheila; Vulule, John; Hamel, Mary J; Laserson, Kayla

2010-08-01

To evaluate mortality and morbidity among internally displaced persons (IDPs) who relocated in a demographic surveillance system (DSS) area in western Kenya following post-election violence. In 2007, 204 000 individuals lived in the DSS area, where field workers visit households every 4 months to record migrations, births and deaths. We collected data on admissions among children < 5 years of age in the district hospital and developed special questionnaires to record information on IDPs. Mortality, migration and hospitalization rates among IDPs and regular DSS residents were compared, and verbal autopsies were performed for deaths. Between December 2007 and May 2008, 16 428 IDPs migrated into the DSS, and over half of them stayed 6 months or longer. In 2008, IDPs aged 15-49 years died at higher rates than regular residents of the DSS (relative risk, RR: 1.34; 95% confidence interval, CI: 1.004-1.80). A greater percentage of deaths from human immunodeficiency virus (HIV) infection occurred among IDPs aged > or = 5 years (53%) than among regular DSS residents (25-29%) (P < 0.001). Internally displaced children < 5 years of age did not die at higher rates than resident children but were hospitalized at higher rates (RR: 2.95; 95% CI: 2.44-3.58). HIV-infected internally displaced adults in conflict-ridden parts of Africa are at increased risk of HIV-related death. Relief efforts should extend to IDPs who have relocated outside IDP camps, particularly if afflicted with HIV infection or other chronic conditions.

Melatonin modulates adiponectin expression on murine colitis with sleep deprivation.

PubMed

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

2016-09-07

To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA. Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P < 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection. This study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated anti-inflammatory effects on colitis with sleep deprivation.

Dark Sky Scotland

NASA Astrophysics Data System (ADS)

Hillier, D.

2008-06-01

Dark Sky Scotland (DSS) 2006-2008 is a nationwide programme of public and educational astronomy events. It demonstrates successful national partnerships with non-astronomy organisations and effective ways of delivering events in remote rural communities. DSS is looking for international partners for IYA2009.

Clinical significance of cigarette smoking and dust exposure in pulmonary alveolar proteinosis: a Korean national survey.

PubMed

Hwang, Ji An; Song, Joo Han; Kim, Jung Hoon; Chung, Man Pyo; Kim, Dong Soon; Song, Jin Woo; Kim, Young Whan; Choi, Sun Mi; Cha, Seung Ick; Uh, Soo Taek; Park, Choon-Sik; Jeong, Sung Hwan; Park, Yong Bum; Lee, Hong Lyeol; Shin, Jong Wook; Lee, Eun Joo; Jegal, Yangjin; Lee, Hyun Kyung; Park, Jong Sun; Park, Moo Suk

2017-11-21

This study aimed to investigate clinical characteristics of Korean PAP patients and to examine the potential risk factors of PAP. We retrospectively reviewed medical records of 78 Korean PAP patients diagnosed between 1993 and 2014. Patients were classified into two groups according to the presence/absence of treatment (lavage). Clinical and laboratory features were compared between the two groups. Of the total 78 PAP patients, 60% were male and median age at diagnosis was 47.5 years. Fifty three percent were ever smokers (median 22 pack-years) and 48% had a history of dust exposure (metal 26.5%, stone or sand 20.6%, chemical or paint 17.7%, farming dust 14.7%, diesel 14.7%, textile 2.9%, and wood 2.9%). A history of cigarette smoking or dust exposure was present in 70.5% of the total PAP patients, with 23% having both of them. Patients who underwent lavage (n = 38) presented symptoms more frequently (38/38 [100%] vs. 24/40 [60%], P < 0.001) and had significantly lower PaO 2 and DL CO with higher D(A-a)O 2 at the onset of disease than those without lavage (n = 40) (P = 0.006, P < 0.001, and P = 0.036, respectively). Correspondingly, the distribution of disease severity score (DSS) differed significantly between the two groups (P = 0.001). Based on these, when the total patients were categorized according to DSS (low DSS [DSS 1-2] vs. high DSS [DSS 3-5]), smoking status differed significantly between the two groups with the proportion of current smokers significantly higher in the high DSS group (11/22 [50%] vs. 7/39 [17.9%], P = 0.008). Furthermore, current smokers had meaningfully higher DSS and serum CEA levels than non-current smokers (P = 0.011 and P = 0.031), whereas no difference was found between smokers and non-smokers. Regarding type of exposed dust, farming dust was significantly associated with more severe form of PAP (P = 0.004). A considerable proportion of PAP patients had a history of cigarette smoking and/or dust exposure, suggestive of their possible roles in the development of PAP. Active cigarette smoking at the onset of PAP is associated with the severity of PAP.

BTZO-15, an ARE-Activator, Ameliorates DSS- and TNBS-Induced Colitis in Rats

PubMed Central

Yukitake, Hiroshi; Kimura, Haruhide; Suzuki, Hirobumi; Tajima, Yasukazu; Sato, Yoshimi; Imaeda, Toshihiro; Kajino, Masahiro; Takizawa, Masayuki

2011-01-01

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that are primarily represented by ulcerative colitis and Crohn's disease. The etiology of IBD is not well understood; however, oxidative stress is considered a potential etiological and/or triggering factor for IBD. We have recently reported the identification of BTZO-1, an activator of antioxidant response element (ARE)-mediated gene expression, which protects cardiomyocytes from oxidative stress-induced insults. Here we describe the potential of BTZO-15, an active BTZO-1 derivative for ARE-activation with a favorable ADME-Tox profile, for the treatment of IBD. BTZO-15 induced expression of heme oxygenase-1 (HO-1), an ARE-regulated cytoprotective protein, and inhibited NO-induced cell death in IEC-18 cells. Large intestine shortening, rectum weight gain, diarrhea, intestinal bleeding, and an increase in rectal myeloperoxidase (MPO) activity were observed in a dextran sulfate sodium (DSS)-induced colitis rat model. Oral administration of BTZO-15 induced HO-1 expression in the rectum and attenuated DSS-induced changes. Furthermore BTZO-15 reduced the ulcerated area and rectal MPO activity in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats without affecting rectal TNF-α levels. These results suggest that BTZO-15 is a promising compound for a novel IBD therapeutic drug with ARE activation properties. PMID:21853095

The utility of abbreviated patient-reported outcomes for predicting survival in early stage colorectal cancer.

PubMed

Hsu, Tina; Speers, Caroline H; Kennecke, Hagen F; Cheung, Winson Y

2017-05-15

Patient-reported outcomes (PROs) are increasingly used in clinical settings. Prior research suggests that PROs collected at baseline may be associated with cancer survival, but most of those studies were conducted in patients with breast or lung cancer. The objective of this study was to determine the correlation between prospectively collected PROs and cancer-specific outcomes in patients with early stage colorectal cancer. Patients who had newly diagnosed stage II or III colorectal cancer from 2009 to 2010 and had a consultation at the British Columbia Cancer Agency completed the brief Psychosocial Screen for Cancer (PSSCAN) questionnaire, which collects data on patients' perceived social supports, quality of life (QOL), anxiety and depression, and general health. PROs from the PSSCAN were linked with the Gastrointestinal Cancers Outcomes Database, which contains information on patient and tumor characteristics, treatment details, and cancer outcomes. Cox regression models were constructed for overall survival (OS), and Fine and Gray regression models were developed for disease-specific survival (DSS). In total, 692 patients were included. The median patient age was 67 years (range, 26-95 years), and the majority had colon cancer (61%), were diagnosed with stage III disease (54%), and received chemotherapy (58%). In general, patients felt well supported and reported good overall health and QOL. On multivariate analysis, increased fatigue was associated with worse OS (hazard ratio [HR], 1.99; P = .00007) and DSS (HR, 1.63; P = .03), as was lack of emotional support (OS: HR, 4.36; P = .0003; DSS: HR, 1.92; P = .02). Although most patients described good overall health and QOL and indicated that they were generally well supported, patients who experienced more pronounced fatigue or lacked emotional support had a higher likelihood of worse OS and DSS. These findings suggest that abbreviated PROs can inform and assist clinicians to identify patients who have a worse prognosis and may need more vigilant follow-up. Cancer 2017;123:1839-1847. © 2017 American Cancer Society. © 2016 American Cancer Society.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Xue-Feng; Ouyang, Zi-Jun; Feng, Li-Li

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