Sample records for acute dextran sodium

  1. 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

  2. Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway.

    PubMed

    Wu, Dacheng; Wu, Keyan; Zhu, Qingtian; Xiao, Weiming; Shan, Qing; Yan, Zhigang; Wu, Jian; Deng, Bin; Xue, Yan; Gong, Weijuan; Lu, Guotao; Ding, Yanbing

    2018-01-01

    Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF- α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1 β ) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.

  3. 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.

  4. Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway

    PubMed Central

    Wu, Dacheng; Wu, Keyan; Zhu, Qingtian; Xiao, Weiming; Shan, Qing; Yan, Zhigang; Wu, Jian; Deng, Bin; Xue, Yan; Gong, Weijuan

    2018-01-01

    Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1β) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation. PMID:29507526

  5. 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

  6. Fermented herbal formula KIOM-MA-128 protects against acute colitis induced by dextran sodium sulfate in mice.

    PubMed

    Kim, Dong-Gun; Lee, Mi-Ra; Yoo, Jae-Myung; Park, Kwang-Il; Ma, Jin-Yeul

    2017-07-05

    Colitis is a well-known subtype of inflammatory bowel disease and is caused by diverse factors. Previous research has shown that KIOM-MA elicits anti-inflammatory and anti-allergic effects on various diseases. KIOM-MA-128, our novel herbal formula, was generated from KIOM-MA using probiotics to improve the therapeutic efficacy. We investigated whether KIOM-MA-128 has protective activity in a mouse model of acute colitis induced by dextran sodium sulfate (DSS). Colitis was induced by DSS administered to ICR mice in drinking water. KIOM-MA-128 (125 or 250 mg/kg) was orally administered once per day. The body weights of the mice were measured daily, and colonic endoscopies were performed at 5 and 8 days. Colon length as well as histological and cytokine changes were observed at the end of drug administration. KIOM-MA-128 has pharmacological activity in an acute colitis model. KIOM-MA-128 reduced the loss of body weight and disease activity index (DAI) and inhibited the abnormally short colon lengths and the colonic damage in this mouse model of acute colitis. Moreover, KIOM-MA-128 suppressed pro-inflammatory cytokine expression and maintained the integrity of the tight junctions during DSS-induced colitis. The results indicated that KIOM-MA-128 protects against DSS-induced colitis in mice and suggested that this formula might be a candidate treatment for inflammatory bowel disease (IBD).

  7. Heme oxygenase-1 ameliorates dextran sulfate sodium-induced acute murine colitis by regulating Th17/Treg cell balance.

    PubMed

    Zhang, Liya; Zhang, Yanjie; Zhong, Wenwei; Di, Caixia; Lin, Xiaoliang; Xia, Zhenwei

    2014-09-26

    Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a group of autoimmune diseases characterized by nonspecific inflammation in the gastrointestinal tract. Recent investigations suggest that activation of Th17 cells and/or deficiency of regulatory T cells (Treg) is involved in the pathogenesis of IBD. Heme oxygenase (HO)-1 is a protein with a wide range of anti-inflammatory and immune regulatory function, which exerts significantly protective roles in various T cell-mediated diseases. In this study, we aim to explore the immunological regulation of HO-1 in the dextran sulfate sodium-induced model of experimental murine colitis. BALB/c mice were administered 4% dextran sulfate sodium orally; some mice were intraperitoneally pretreated with HO-1 inducer hemin or HO-1 inhibitor stannum protoporphyrin IX. The results show that hemin enhances the colonic expression of HO-1 and significantly ameliorates the symptoms of colitis with improved histological changes, accompanied by a decreased proportion of Th17 cells and increased number of Tregs in mesenteric lymph node and spleen. Moreover, induction of HO-1 down-regulates retinoic acid-related orphan receptor γt expression and IL-17A levels, while promoting Treg-related forkhead box p3 (Foxp3) expression and IL-10 levels in colon. Further study in vitro revealed that up-regulated HO-1 switched the naive T cells to Tregs when cultured under a Th17-inducing environment, which involved in IL-6R blockade. Therefore, HO-1 may exhibit anti-inflammatory activity in the murine model of acute experimental colitis via regulating the balance between Th17 and Treg cells, thus providing a possible novel therapeutic target in IBD. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    PubMed

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

    2017-09-01

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

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

    PubMed Central

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

    2017-01-01

    Fasting-refeeding in mice induces transient hyperproliferation of colonic epithelial cells, which is dependent on the lactate produced as a metabolite of commensal bacteria. We attempted to manipulate colonic epithelial cell turnover with intermittent fasting to prompt recovery from acute colitis. Acute colitis was induced in C57BL/6 mice by administration of dextran sulfate sodium in the drinking water for 5 days. From day 6, mice were fasted for 36 h and refed normal bait, glucose powder, or lactylated high-amylose starch. On day 9, colon tissues were subjected to analysis of histology and cytokine expression. The effect of lactate on the proliferation of colonocytes was assessed by enema in vivo and primary culture in vitro. Intermittent fasting resulted in restored colonic crypts and less expression of interleukin-1β and interleukin-17 in the colon than in mice fed ad libitum. Administration of lactate in the colon at refeeding time by enema or by feeding lactylated high-amylose starch increased the number of regenerating crypts. Addition of lactate but not butyrate or acetate supported colony formation of colonocytes in vitro. In conclusion, intermittent fasting in the resolution phase of acute colitis resulted in better recovery of epithelial cells and reduced inflammation. PMID:28955126

  10. Therapeutic Effects of 6-Gingerol, 8-Gingerol, and 10-Gingerol on Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis in Rats.

    PubMed

    Zhang, Feng; Ma, Na; Gao, Yong-Feng; Sun, Li-Li; Zhang, Ji-Guo

    2017-09-01

    Ulcerative colitis is one of the most common types of inflammatory bowel disease and is multifactorial and relapsing. 6-Gingerol, a component of gingerols extracted from ginger (Zingiber officinale), has been reported to improve ulcerative colitis. The present study aims to investigate the therapeutic efficacy of two analogous forms of 6-gingerol, 8-gingerol, and 10-gingerol, on ulcerative colitis. Colitis was induced in rats through consumption of 5% (w/v) dextran sulfate sodium drinking water for 7 consecutive days. 6-Gingerol, 8-gingerol, and 10-gingerol were then given intraperitoneally at doses of 30 mg kg -1  d -1 for another 7 days, respectively. Body weight change, disease activity index, inflammatory cytokines, and oxidative stress indices were measured, and the colonic tissue injuries were assessed macroscopically and histopathologically. Results showed that all three gingerols attenuated colitic symptoms evoked by dextran sulfate sodium, significantly elevated superoxide dismutase activity, decreased malondialdehyde levels and myeloperoxidase activity in the colon tissue, and markedly reduced the content of tumor necrosis factor alpha and Interleukin 1 beta in the serum. Histological observations showed that all three gingerols obviously accelerated mucosal damage healing. It is concluded that 6-gingerol, 8-gingerol, and 10-gingerol, the three analogues, have a strong and relatively equal efficacy in the treatment of colitis. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Acute and chronic exposure of rat intestinal mucosa to dextran promotes SGLTI-mediated glucose transport.

    PubMed

    Debnam, E S; Denholm, E E; Grimble, G K

    1998-08-01

    The intestinal handling of dextran, an alpha-1,6-linked glucose polymer, is poor compared with starch, and some ingested dextran might therefore reach the lower small intestine. As luminal sugar up-regulates SGLT1 (sodium-dependent glucose transporter) locally, we report the effects of a dextran-enriched diet on jejunal and ileal brush border membrane (BBM) glucose uptake. Rats were maintained on a diet containing 65% maltodextrin or 32.5% maltodextrin + 32.5% dextran (10 kD or 40 kD) for 8-10 days, and the kinetics of phlorizin-sensitive [3H]-glucose uptake by purified BBM vesicles was determined. Ingestion of 40-kD but not 10-kD dextran increased Vmax for jejunal and ileal glucose uptake (+64.3% and +61.8% respectively, both P < 0.02). The transport response to 40-kD dextran was in keeping with lower levels of expired H2 at the end of the feeding period. High-performance liquid chromatography (HPLC) analysis of luminal contents indicated extensive hydrolysis of ingested dextran. Finally, 3-h jejunal exposure to 40-kD dextran in vivo increased the Vmax for glucose uptake by jejunal BBM. It is likely that increased SGLT1-mediated glucose uptake after short or longer term mucosal exposure to dextran results from luminal dextran per se or a hydrolysis product. The clinical implications of this up-regulation are discussed.

  12. Opposite Role of Tumor Necrosis Factor Receptors in Dextran Sulfate Sodium-Induced Colitis in Mice

    PubMed Central

    Wang, Yi; Liu, Guijun; Wang, Renxi; Xiao, He; Li, Xinying; Hou, Chunmei; Shen, Beifen; Guo, Renfeng; Li, Yan; Shi, Yanchun; Chen, Guojiang

    2012-01-01

    Tumor necrosis factor-α (TNF-α) is a key factor for the pathogenesis of inflammatory bowel diseases (IBD), whose function is known to be mediated by TNF receptor 1 (TNFR1) or 2. However, the precise role of the two receptors in IBD remains poorly understood. Herein, acute colitis was induced by dextran sulfate sodium (DSS) instillation in TNFR1 or 2−/− mice. TNFR1 ablation led to exacerbation of signs of colitis, including more weight loss, increased mortality, colon shortening and oedema, severe intestinal damage, and higher levels of myeloperoxidase compared to wild-type counterparts. While, TNFR2 deficiency had opposite effects. This discrepancy was reflected by alteration of proinflammatory cytokine and chemokine production in the colons. Importantly, TNFR1 ablation rendered enhanced apoptosis of colonic epithelial cells and TNFR2 deficiency conferred pro-apoptotic effects of lamina propria (LP)-immune cells, as shown by the decreased ratio of Bcl-2/Bax and enhanced nuclear factor (NF)-κB activity. PMID:23285227

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

    PubMed

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

    2018-06-01

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

  14. 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.

  15. 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

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

    PubMed

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

    2016-02-01

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

  17. 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...

  18. One-step microwave synthesis of photoluminescent carbon nanoparticles from sodium dextran sulfate water solution

    NASA Astrophysics Data System (ADS)

    Kokorina, Alina A.; Goryacheva, Irina Y.; Sapelkin, Andrei V.; Sukhorukov, Gleb B.

    2018-04-01

    Photoluminescent (PL) carbon nanoparticles (CNPs) have been synthesized by one-step microwave irradiation from water solution of sodium dextran sulfate (DSS) as the sole carbon source. Microwave (MW) method is very simple and cheap and it provides fast synthesis of CNPs. We have varied synthesis time for obtaining high luminescent CNPs. The synthesized CNPs exhibit excitation-dependent photoluminescent. Final CNPs water solution has a blue- green luminescence. CNPs have low cytotoxicity, good photostability and can be potentially suitable candidates for bioimaging, analysis or analytical tests.

  19. Pulmonary permeability assessed by fluorescent-labeled dextran instilled intranasally into mice with LPS-induced acute lung injury.

    PubMed

    Chen, Honglei; Wu, Shaoping; Lu, Rong; Zhang, Yong-guo; Zheng, Yuanyuan; Sun, Jun

    2014-01-01

    Several different methods have been used to assess pulmonary permeability in response to acute lung injury (ALI). However, these methods often involve complicated procedures and algorithms that are difficult to precisely control. The purpose of the current study is to establish a feasible method to evaluate alterations in lung permeability by instilling fluorescently labeled dextran (FITC-Dextran) intranasally. For the mouse model of direct ALI, lipopolysaccharide (LPS) was administered intranasally. FITC-Dextran was instilled intranasally one hour before the mice were euthanized. Plasma fluorescence intensities from the LPS group were significantly higher than in the control group. To determine the reliability and reproducibility of the procedure, we also measured the lung wet-to-dry weight ratio, the protein concentration of the bronchoalveolar lavage fluid, tight and adherens junction markers and pathological changes. Consistent results were observed when the LPS group was compared with the control group. Simultaneously, we found that the concentration of plasma FITC-Dextran was LPS dose-dependent. The concentration of plasma FITC-Dextran also increased with initial intranasal FITC-Dextran doses. Furthermore, increased fluorescence intensity of plasma FITC-Dextran was found in the intraperitoneally LPS-induced ALI model. In conclusion, the measurement of FITC-Dextran in plasma after intranasal instillation is a simple, reliable, and reproducible method to evaluate lung permeability alterations in vivo. The concentration of FITC-Dextran in the plasma may be useful as a potential peripheral biomarker of ALI in experimental clinical studies.

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

    PubMed

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

    2014-03-01

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

  1. Partial replacement of dietary linoleic acid with long chain n-3 polyunsaturated fatty acids protects against dextran sulfate sodium-induced colitis in rats.

    PubMed

    Tyagi, Anupama; Kumar, Uday; Santosh, Vadakattu Sai; Reddy, Suryam; Mohammed, Saazida Bhanu; Ibrahim, Ahamed

    2014-12-01

    Imbalances in the dietary n-6 and n-3 polyunsaturated fatty acids have been implicated in the increased prevalence of inflammatory bowel disease. This study investigated the effects of substitution of linoleic acid with long chain n-3 polyunsaturated fatty acids and hence decreasing n-6:n-3 fatty acid ratio on inflammatory response in dextran sulfate sodium induced colitis. Male weanling Sprague Dawley rats were fed diets with n-6:n-3 fatty acid in the ratios of 215,50,10 or 5 for 3 months and colitis was induced by administration of dextran sulfate sodium in drinking water during last 11 days. Decreasing the dietary n-6:n-3 fatty acid ratio to 10 and 5 significantly attenuated the severity of colitis as evidenced by improvements in clinical symptoms, reversal of shortening of colon length, reduced severity of anemia, preservation of colonic architecture as well as reduced colonic mucosal myeloperoxidase activity. This protection was associated with suppression of colonic mucosal proinflammatory mediators such as TNFα, IL-1β and nitric oxide. These findings suggest that long chain n-3 polyunsaturated fatty acids at a level of 3.0 g/kg diet (n-6:n-3 ratio of 10) prevents dextran sulfate sodium induced colitis by suppressing the proinflammatory mediators. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. 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.

  3. 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.

  4. 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.

  5. Resuscitation of severe uncontrolled hemorrhage: 7.5% sodium chloride/6% dextran 70 vs 0.9% sodium chloride.

    PubMed

    Stern, S A; Jwayyed, S; Dronen, S C; Wang, X

    2000-08-01

    Resuscitation studies of hypertonic saline using controlled and uncontrolled hemorrhage models yield conflicting results with regard to efficacy. These disparate results reflect the use of models and resuscitation regimens that are not comparable between studies. This study evaluated the effects of comparable and clinically relevant resuscitation regimens of 7.5% sodium chloride/6% dextran 70 (HSD) and 0.9% sodium chloride (NS) in a near-fatal uncontrolled hemorrhage model. Thirty-six swine (14.2 to 21.4 kg) with 4-mm aortic tears were bled to a pulse pressure of 5 mm Hg (40-45 mL/kg). The animals were resuscitated with either NS or HSD administered in volumes that provided equivalent sodium loads at similar rates. Group II (n = 12) was resuscitated with 80 mL/kg of NS at a rate of 4 mL/kg/min. Group III (n = 12) received 9.6 mL/kg of HSD at a rate of 0.48 mL/kg/min. In both groups, crystalloid resuscitation was followed by shed blood infusion (30 mL/kg) at a rate of 2 mL/kg/min. Group I (controls; n = 12) were not resuscitated. One-hour mortality was significantly greater in group I (92%) as compared with group II (33%) and group III (33%) (Fisher's exact test; p = 0.004). Intraperitoneal hemorrhage was significantly greater in group II (34 +/- 20 mL/kg) and group III (31 +/- 13 mL/ kg) as compared with group I (5 +/- 2 mL/kg) (ANOVA; p < 0.05). There was no significant difference in hemodynamic parameters between groups II and III. In this model of severe uncontrolled hemorrhage, resuscitation with HSD or NS, administered in volumes that provided equivalent sodium loads at similar rates, had similar effects on mortality, hemodynamic parameters, and hemorrhage from the injury site.

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

    PubMed

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

    2017-02-01

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

  7. Dietary tryptophan alleviates dextran sodium sulfate-induced colitis through aryl hydrocarbon receptor in mice.

    PubMed

    Islam, Jahidul; Sato, Shoko; Watanabe, Kouichi; Watanabe, Takaya; Ardiansyah; Hirahara, Keisuke; Aoyama, Yukihide; Tomita, Shuhei; Aso, Hisashi; Komai, Michio; Shirakawa, Hitoshi

    2017-04-01

    Ulcerative colitis is the typical progression of chronic inflammatory bowel disease. Amino acids, particularly tryptophan, have been reported to exert a protective effect against colitis induced by dextran sodium sulfate (DSS), but the precise underlying mechanisms remain incompletely clarified. Tryptophan metabolites are recognized to function as endogenous ligands for aryl hydrocarbon receptor (Ahr), which is a critical regulator of inflammation and immunity. Thus, we conducted this study to investigate whether dietary tryptophan supplementation protects against DSS-induced colitis by acting through Ahr. Female wild-type (WT) and Ahr-deficient (knockout; KO) mice (10-12 weeks old) were divided into four groups and fed either a control or 0.5% tryptophan diet. The tryptophan diet ameliorated DSS-induced colitis symptoms and severity in WT mice but not in KO mice, and the diet reduced the mRNA expression of Il-6, Tnfα, Il-1β and the chemokines Ccl2, Cxcl1 and Cxcl2 in the WT groups. Furthermore, Il-22 and Stat3 mRNA expression in the colon was elevated in WT mice fed with the tryptophan diet, which mainly protected epithelial layer integrity, and Ahr also modulated immune homeostasis by regulating Foxp3 and Il-17 mRNA expression. These data suggest that tryptophan-containing diet might ameliorate DSS-induced acute colitis and regulate epithelial homeostasis through Ahr. Thus, tryptophan could serve as a promising preventive agent in the treatment of ulcerative colitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Negative impact of bone-marrow-derived mesenchymal stem cells on dextran sulfate sodium-induced colitis

    PubMed Central

    Nam, Young-Sun; Kim, Nayoun; Im, Keon-Il; Lim, Jung-Yeon; Lee, Eun-Sol; Cho, Seok-Goo

    2015-01-01

    AIM: To investigate the effects of mesenchymal stem cells (MSCs) on dextran sulfate sodium-induced inflammatory bowel disease (IBD). METHODS: C57BL/6 mice were fed 3.5% (g/L) dextran sulfate sodium. On day seven, the mice received intraperitoneal injections of 1 × 106 MSCs. The survival rate, disease activity index values, and body weight, were monitored daily. On day ten, colon lengths and histopathologic changes were assessed. In addition, immunoregulatory changes following MSC administration were evaluated by determining the levels of effector T cell responses in the spleen and mesenteric lymph nodes, and the expression levels of inflammatory cytokines in homogenized colons. RESULTS: Intraperitoneal administration of MSCs did not prevent development of colitis and did not reduce the clinicopathologic severity of IBD. No significant difference was evident in either survival rate or disease activity index score between the control and MSC-treated group. Day ten-sacrificed mice exhibited no significant difference in either colon length or histopathologic findings. Indeed, the MSC-treated group exhibited elevated levels of interleukin (IL)-6 and transforming growth factor-β, and a reduced level of IL-10, in spleens, mesenteric lymph nodes, and homogenized colons. The IL-17 level was lower in the mesenteric lymph nodes of the MSC-treated group (P = 0.0126). In homogenized colons, the IL-17 and tumor necrosis factor-α (P = 0.0092) expression levels were also lower in the treated group. CONCLUSION: MSC infusion provided no significant histopathologic or clinical improvement, thus representing a limited therapeutic approach for IBD. Functional enhancement of MSCs is needed in further study. PMID:25717235

  9. 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.

  10. Nonfouling Characteristics of Dextran-Containing Surfaces

    PubMed Central

    Martwiset, Surangkhana; Koh, Anna E.; Chen, Wei

    2008-01-01

    Hydroxyl groups in dextrans have been selectively oxidized to aldehyde groups by sodium periodate in a controlled fashion with percentage of conversion ranging from 6% to 100%. Dextrans (10 k, 70 k, 148 k, 500 k, and 2 000 kDa) and oxidized 10 k dextrans have been successfully grafted to functionalized silicon surfaces. The effect of molecular weight on protein adsorption is not nearly as striking as that of the extent of oxidation. When ∼ 25% of the hydroxyl groups have been converted to aldehyde groups, there is negligible protein adsorption on surfaces containing the oxidized polysaccharides. Conformations of grafted polymers depend strongly on their chemical structures, i.e. the relative amounts of –OH and –CHO groups. That the dependence of the chain conformation as well as the protein resistance on the balance of the hydrogen bond donors (-OH) and the acceptors (-OH and –CHO) implies the importance of chemical structure of surface molecules, specifically the interactions between surface and surrounding water molecules on protein adsorption. Oxidized dextrans are potential poly(ethylene glycol)-alternatives for nonfouling applications. PMID:16952261

  11. Depression of fractional sodium reabsorption by the proximal tubule of the dog without sodium diuresis

    PubMed Central

    Howards, Stuart S.; Davis, Bernard B.; Knox, Franklyn G.; Wright, Fred S.; Berliner, Robert W.

    1968-01-01

    The effect of infusions of hyperoncotic solutions on fractional sodium reabsorption by the proximal tubule of the dog was studied by the recollection micropuncture method. Tubule fluid to plasma inulin concentration ratios were measured for identified proximal tubule segments before and after infusion of 25% albumin or dextran solutions. Results were compared with changes in fractional reabsorption during saline diuresis. Plasma volume increased 66% ± SE 5.8 after infusion of albumin solution and 94% ± SE 8.2 after infusion of dextran solution. Fractional sodium reabosorption by the proximal tubule was depressed after infusion of both of these hyperoncotic solutions. Nevertheless, changes in sodium excretion after infusion of albumin and dextran were small. In contrast, after infusions of isotonic sodium chloride solution, which increased plasma volume 61% ± SE 5.8, a decrease in fractional reabsorption of 50.7% ± SE 7.2 was associated with large changes in sodium excretion. PMID:5658588

  12. The impact of the molecular weight of dextran on formation of whey protein isolate (WPI)-dextran conjugates in fibers produced by needleless electrospinning after annealing.

    PubMed

    Turan, Deniz; Gibis, Monika; Gunes, Gurbuz; Baier, Stefan K; Weiss, Jochen

    2018-04-25

    The conjugation reaction of electrospun fibers of a mixture of whey protein isolate (WPI) and dextran using different molecular weights (40, 70, and 100 kDa) and mixing ratios was studied. This study includes the electrospinnability of a mixture of WPI and dextran, and the conjugation reaction between them via the initial stage of the Maillard reaction. The WPI-dextran fibers were characterized using optical and transmission electron microscopy. The covalent attachment of dextran to WPI was confirmed using sodium-dodecyl-sulfate-polyacrylamide gel-electrophoresis with protein and glycoprotein staining. Both 70 and 100 kDa of dextran and WPI at mixing ratios of 2 : 1 and 3 : 1 in phosphate buffer (30 mM, pH 6.5) were electrospun using needleless electrospinning. The solution concentration of the mixture was 50 wt% (33.3/37.5 wt% for dextran/16.5/12.5 wt% for WPI). The optimal conjugation conditions chosen from the experiments were a mixture of dextran (70 kDa)-WPI at 3 : 1 (75% relative humidity, 60 °C, 48 h).

  13. Dietary Propolis Ameliorates Dextran Sulfate Sodium-Induced Colitis and Modulates the Gut Microbiota in Rats Fed a Western Diet.

    PubMed

    Wang, Kai; Jin, Xiaolu; You, Mengmeng; Tian, Wenli; Le Leu, Richard K; Topping, David L; Conlon, Michael A; Wu, Liming; Hu, Fuliang

    2017-08-14

    Propolis is an important hive product and considered beneficial to health. However, evidence of its potential for improving gut health is still lacking. Here we use rats to examine whether dietary supplementation with propolis could be used as a therapy for ulcerative colitis. Rats were fed with a Western style diet alone (controls) or supplemented with different amounts of Chinese propolis (0.1%, 0.2%, and 0.3%) to examine effects on acute colitis induced by 3% dextran sulphate sodium (DSS) in drinking water. Propolis at 0.3%, but not lower levels, significantly improved colitis symptoms compared with the control group, with a less pronounced disease activity index (DAI) ( p < 0.001), a significant increase in colon length/weight ratio ( p < 0.05) and an improved distal colon tissue structure as assessed by histology. Although short chain fatty acid levels in digesta were not altered by propolis supplementation, 16S rRNA phylogenetic sequencing revealed a significant increase in gut microbial diversity after 21 days of 0.3% propolis supplementation compared with controls including a significant increase in bacteria belonging to the Proteobacteria and Acidobacteria phyla. This is the first study to demonstrate that propolis can attenuate DSS-induced colitis and provides new insight into diet-microbiota interactions during inflammatory bowel disease.

  14. 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.

  15. Dextran Preserves Native Corneal Structure During Decellularization.

    PubMed

    Lynch, Amy P; Wilson, Samantha L; Ahearne, Mark

    2016-06-01

    Corneal decellularization has become an increasingly popular technique for generating scaffolds for corneal regeneration. Most decellularization procedures result in tissue swelling, thus limiting their application. Here, the use of a polysaccharide, dextran, to reduce swelling and conserve the native corneal structure during decellularization was investigated. Corneas were treated with 1% Triton X-100, 0.5% sodium dodecyl sulfate, and nucleases under constant rotation followed by extensive washing. To reduce swelling, decellularization solutions were supplemented with 5% dextran either throughout the whole decellularization process or during the washing cycles only. Quantitative analysis of DNA content showed a 96% reduction after decellularization regardless of the addition of dextran. Dextran resulted in a significant reduction in swelling from 3.85 ± 0.43 nm without to 1.94 ± 0.29-2.01 ± 0.37 nm (p < 0.05) remaining at similar dimensions to the native tissue (1.73 ± 0.23 nm). Tissue transparency was restored to all decellularized corneas following submersion in glycerol. Transmission electron microscopy (TEM) analysis found that dextran must be present throughout the decellularization protocol to preserve the native corneal architecture, anisotropy analysis demonstrated comparable results (0.22 ± 0.03) to the native cornea (0.24 ± 0.02), p > 0.05. Dextran can counteract the detrimental effects of decellularizing agents on the biomechanical properties of the tissue resulting in similar compressive moduli (mean before decellularization: 5.40 ± 1.18 kPa; mean after decellularization with dextran: 5.64 ± 1.34 kPa, p > 0.05). Cells remained viable in the presence of decellularized scaffolds. The findings of this study indicate that dextran not only prevents significant corneal swelling during decellularization but also enhances the maintenance of the native corneal ultrastructure.

  16. Cardiovascular effect of 7.5% sodium chloride-dextran infusion after thermal injury.

    PubMed

    Murphy, J T; Horton, J W; Purdue, G F; Hunt, J L

    1999-10-01

    Clinical study can help determine the safety and cardiovascular and systemic effects of an early infusion of 7.5% sodium chloride in 6% dextran-70 (hypertonic saline-dextran-70 [HSD]) given as an adjuvant to a standard resuscitation with lactated Ringer (RL) solution following severe thermal injury. Prospective clinical study. Intensive care unit of tertiary referral burn care center. Eighteen patients with thermal injury over more than 35% of the total body surface area (TBSA) (range, 36%-71%) were studied. Eight patients (mean +/- SEM, 48.2% +/- 2% TBSA) received a 4-mL/kg HSD infusion approximately 3.5 hours (range, 1.5-5.0 hours) after thermal injury in addition to routine RL resuscitation. Ten patients (46.0% +/- 6% TBSA) received RL resuscitation alone. Pulmonary artery catheters were employed to monitor cardiac function, while hemodynamic, metabolic, and biochemical measurements were taken for 24 hours. Serum troponin I levels, while detectable in all patients, were significantly lower after HSD compared with RL alone (mean +/- SEM, 0.45 +/- 0.32 vs 1.35 +/- 0.35 microg/L at 8 hours, 0.88 +/- 0.55 vs 2.21 +/- 0.35 microg/L at 12 hours). While cardiac output increased proportionately between 4 and 24 hours in both groups (from 5.79 +/- 0.8 to 9.45 +/- 1.1 L/min [mean +/- SEM] for HSD vs from 5.4 +/- 0.4 to 9.46 +/- 1.22 L/min for RL), filling pressure (central venous pressure and pulmonary capillary wedge pressure) remained low for 12 hours after HSD infusion (P = .048). Total fluid requirements at 8 hours (2.76 +/- 0.7 mL/kg per each 1% TBSA burned [mean +/- SEM] for HSD vs 2.67 +/- 0.24 mL/kg per each 1% TBSA burned for RL) and 24 hours (6.11 +/- 4.4 vs 6.76 +/- 0.75 mL/kg per each 1% TBSA burned) were similar. Blood pressure remained unchanged, and serum sodium levels did not exceed 150 +/- 2 mmol/L (mean +/- SD) in either group. The absence of deleterious hemodynamic or metabolic side effects following HSD infusion in patients with major thermal injury

  17. Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism.

    PubMed

    Qu, Chang; Yuan, Zhong-Wen; Yu, Xiu-Ting; Huang, Yan-Feng; Yang, Guang-Hua; Chen, Jian-Nan; Lai, Xiao-Ping; Su, Zi-Ren; Zeng, Hui-Fang; Xie, Ying; Zhang, Xiao-Jun

    2017-07-01

    Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C 15 H 26 O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given

  18. Protein resistance of dextran and dextran-PEG copolymer films

    PubMed Central

    Kozak, Darby; Chen, Annie; Bax, Jacinda; Trau, Matt

    2011-01-01

    The protein resistance of dextran and dextran-poly(ethylene glycol) (PEG) copolymer films was examined on an organosilica particle-based assay support. Comb-branched dextran-PEG copolymer films were synthesized in a two step process using the organosilica particle as a solid synthetic support. Particles modified with increasing amounts (0.1-1.2 mg m−2) of three molecular weights (10 000, 66 900, 400 000 g mol−1) of dextran were found to form relatively poor protein-resistant films compared to dextran-PEG copolymers and previously studied PEG films. The efficacy of the antifouling polymer films was found to be dependent on the grafted amount and its composition, with PEG layers being the most efficient, followed by dextran-PEG copolymers, and dextran alone being the least efficient. Immunoglobulin gamma (IgG) adsorption decreased from ~ 5 to 0.5 mg m−2 with increasing amounts of grafted dextran, but bovine serum albumin (BSA) adsorption increased above monolayer coverage (to ~2 mg m−2) indicating ternary adsorption of the smaller protein within the dextran layer. PMID:21614699

  19. 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.

  20. Contrasting effects of pseudoephedrine and papaverine in dextran sodium sulfate-induced colitis.

    PubMed

    Harris, Norman R; Specian, Robert D; Carter, Patsy R; Morgan, Georgia A

    2008-03-01

    Dextran sodium sulfate (DSS) induces submucosal arteriolar constriction that reduces blood flow to the intestine, and the relevance of this decrease in flow needs further investigation. In the present study we examined the effects of a vasoconstrictor (pseudoephedrine) and a vasodilator (papaverine) on the outcome of DSS-induced colitis. Mice were given DSS in drinking water for 6 days, with enemas on days 0, 1, 3, and 5 containing pseudoephedrine, papaverine, or no drug. At the conclusion of the 6-day protocol a disease activity index comprising weight loss, stool consistency, and rectal bleeding was evaluated, along with intravital microscopy observations of submucosal venular leukocyte and platelet adherence in the proximal colon and terminal ileum. Pseudoephedrine and papaverine had several contrasting effects on the outcome of DSS ingestion: pseudoephedrine induced the highest levels of weight loss, loose stools, venular platelet adherence, and overall disease activity index, while papaverine induced the highest levels of venular leukocyte adherence, but the lowest levels of rectal bleeding, loose stools, and overall disease activity index. The results suggest that vasoconstriction worsens the pathological consequences of DSS in the mouse model of colitis.

  1. 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.

  2. 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.

  3. 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.

  4. Low-level light therapy induces mucosal healing in a murine model of dextran-sodium-sulfate induced colitis.

    PubMed

    Zigmond, Ehud; Varol, Chen; Kaplan, Michail; Shapira, Oz; Melzer, Ehud

    2014-08-01

    The aim of this study was to demonstrate the effect of low-level light therapy (LLLT) in an acute colitis model in mice. Low-level light therapy (LLLT) has been shown to be an effective treatment for various inflammatory processes such as oral mucositis and diabetic foot ulcers. Colitis was induced by dextran sodium sulfate (DSS) in mice in four blinded controlled studies (validation of model, efficacy study, and two studies for evaluation of optimal dose). LLLT was applied to the colon utilizing a small diameter endoscope with an LED-based light source in several wavelengths (440, 660, and 850 nm at 1 J/cm(2)) and then 850 nm at several doses (1, 0.5, 0.25, and 0.1 J/cm(2)). LLLT was initiated 1 day prior to induction of colitis and went on for the 6 day induction period as well as for the following 3-10 days. Dose was controlled by changing exposure time. Disease activity was scored endoscopically and by histopathological assessment. Statistically significant improvement in disease severity was observed in the treatment groups compared with the control groups. The three wavelengths used demonstrated efficacy, and a clear dose-response curve was observed for one of the wavelengths (850 nm). On day 11, colonoscopic scoring in the sham-treated mice increased from 7.9±1.3 to 12.2±2.2, while activity in all treated groups remained stable. Photobiostimulation with LLLT has a significant positive effect on disease progression in mice with DSS colitis.

  5. 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

  6. 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.

  7. Effect of 0.3% Hydroxypropyl Methylcellulose/Dextran Versus 0.18% Sodium Hyaluronate in the Treatment of Ocular Surface Disease in Glaucoma Patients: A Randomized, Double-Blind, and Controlled Study.

    PubMed

    Prabhasawat, Pinnita; Ruangvaravate, Ngamkae; Tesavibul, Nattaporn; Thewthong, Maneerat

    2015-01-01

    To compare the efficacy and safety of 0.3% hydroxypropyl methylcellulose/dextran (HPMC/dextran) and 0.18% sodium hyaluronate (SH) in the treatment of ocular surface disease in patients using antiglaucoma drugs containing preservatives. This was a double-blind, randomized, parallel-group study in 70 glaucoma patients with Ocular Surface Disease Index (OSDI) score greater than 20 points and/or presence of ocular signs. Patients were randomized to receive either preservative-free 0.3% HPMC/dextran (n=35) or preservative-free 0.18% SH (n=35). Treatment was 1 drop in each eye, 4 times a day. Data were collected at baseline, at day 7 and day 28. The groups were homogeneous at baseline. At day 28, both treatments showed significant improvements (P<0.05) in the mean OSDI score, lid skin and lid margin inflammation, conjunctival injection, and expressibility of meibomian glands, corneal staining score, fluorescein tear breakup time (FBUT), and Schirmer I test. However, the mean OSDI score, lid margin inflammation and conjunctival injection showed significant improvements (P<0.05) in the SH group at days 7 and 28, compared to the HPMC/dextran group. FBUT and the Schirmer I test also showed significant improvements (P<0.05) in the SH group compared to the HPMC/dextran group, at day 28. No adverse reactions were observed in either group. Preservative-free artificial tear, 0.3% HPMC/dextran, and 0.18% SH, caused a significant relief of the ocular surface disease in glaucoma patients. However, 0.18% SH led to a greater improvement in ocular signs and symptoms than 0.3% HPMC/dextran.

  8. Impact of RGD amount in dextran-based hydrogels for cell delivery.

    PubMed

    Riahi, Nesrine; Liberelle, Benoît; Henry, Olivier; De Crescenzo, Gregory

    2017-04-01

    Dextran is one of the hydrophilic polymers that is used for hydrogel preparation. As any polysaccharide, it presents a high density of hydroxyl groups, which make possible several types of derivatization and crosslinking reactions. Furthermore, dextran is an excellent candidate for hydrogel fabrication with controlled cell/scaffold interactions as it is resistant to protein adsorption and cell adhesion. RGD peptide can be grafted to the dextran in order to promote selected cell adhesion and proliferation. Altogether, we have developed a novel strategy to graft the RGD peptide sequence to dextran-based hydrogel using divinyl sulfone as a linker. The resulting RGD functionalized dextran-based hydrogels were transparent, presented a smooth surface and were easy to handle. The impact of varying RGD peptide amounts, hydrogel porosity and topology upon human umbilical vein endothelial cell (HUVEC) adhesion, proliferation and infiltration was investigated. Our results demonstrated that 0.1% of RGD-modified dextran within the gel was sufficient to support HUVEC cells adhesion to the hydrogel surface. Sodium chloride was added (i) to the original hydrogel mix in order to form a macroporous structure presenting interconnected pores and (ii) to the hydrogel surface to create small orifices essential for cells migration inside the matrix. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. More complications in patients with septic shock treated with dextran compared with crystalloids.

    PubMed

    Rasmussen, Anders Mølgaard; Jakobsen, Rasmus; Strøm, Thomas; Carlsson, Marcela; Dahler-Eriksen, Bjarne; Toft, Palle

    2015-02-01

    In recent years, the safety-profile of synthetic colloids has been questioned. The purpose of the present study was to elucidate the safety-profile of the colloid dextran-70 in relation to acute kidney injury (AKI) and death. We conducted a retrospective, observational study of patients admitted to our intensive care unit with septic shock and treated with dextran-70 in the period from 1 January 2009 to 31 December 2009. The controls were included from 1 March 2012 to 28 February 2013 when dextran-70 was replaced with crystalloids. There were 91 patients in the dextran group and 150 patients in the non-dextran group. The urinary output was 17.93 ml/kg/24 h in the dextran group and 27.87 in the non-dextran group (p < 0.05). Continuous renal replacement therapy (CRRT) was used in 48% in the dextran group and in 23% in the non-dextran group (p < 0.05). Major bleeding episodes occurred in 32% in the dextran group compared with 15% in the control group (p < 0.05). The 90-day mortality was 42% in the dextran group and 35% in the non-dextran group (p = 0.08). Patients in the dextran group had significantly more bleeding episodes, a higher need for CRRT and a lower urinary output than patients in the non-dextran group. Due to study design, it cannot be concluded that the use of dextran-70 is causally related to the development of AKI.

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

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

    Kanbe, Takamasa; Murai, Rie; Mukoyama, Tomoyuki

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

  11. Assessment of Dextran Antigenicity of Intravenous Iron Preparations with Enzyme-Linked Immunosorbent Assay (ELISA)

    PubMed Central

    Neiser, Susann; Koskenkorva, Taija S.; Schwarz, Katrin; Wilhelm, Maria; Burckhardt, Susanna

    2016-01-01

    Intravenous iron preparations are typically classified as non-dextran-based or dextran/dextran-based complexes. The carbohydrate shell for each of these preparations is unique and is key in determining the various physicochemical properties, the metabolic pathway, and the immunogenicity of the iron-carbohydrate complex. As intravenous dextran can cause severe, antibody-mediated dextran-induced anaphylactic reactions (DIAR), the purpose of this study was to explore the potential of various intravenous iron preparations, non-dextran-based or dextran/dextran-based, to induce these reactions. An IgG-isotype mouse monoclonal anti-dextran antibody (5E7H3) and an enzyme-linked immunosorbent assay (ELISA) were developed to investigate the dextran antigenicity of low molecular weight iron dextran, ferumoxytol, iron isomaltoside 1000, ferric gluconate, iron sucrose and ferric carboxymaltose, as well as isomaltoside 1000, the isolated carbohydrate component of iron isomaltoside 1000. Low molecular weight iron dextran, as well as dextran-based ferumoxytol and iron isomaltoside 1000, reacted with 5E7H3, whereas ferric carboxymaltose, iron sucrose, sodium ferric gluconate, and isolated isomaltoside 1000 did not. Consistent results were obtained with reverse single radial immunodiffusion assay. The results strongly support the hypothesis that, while the carbohydrate alone (isomaltoside 1000) does not form immune complexes with anti-dextran antibodies, iron isomaltoside 1000 complex reacts with anti-dextran antibodies by forming multivalent immune complexes. Moreover, non-dextran based preparations, such as iron sucrose and ferric carboxymaltose, do not react with anti-dextran antibodies. This assay allows to assess the theoretical possibility of a substance to induce antibody-mediated DIARs. Nevertheless, as this is only one possible mechanism that may cause a hypersensitivity reaction, a broader set of assays will be required to get an understanding of the mechanisms that may

  12. Assessment of Dextran Antigenicity of Intravenous Iron Preparations with Enzyme-Linked Immunosorbent Assay (ELISA).

    PubMed

    Neiser, Susann; Koskenkorva, Taija S; Schwarz, Katrin; Wilhelm, Maria; Burckhardt, Susanna

    2016-07-21

    Intravenous iron preparations are typically classified as non-dextran-based or dextran/dextran-based complexes. The carbohydrate shell for each of these preparations is unique and is key in determining the various physicochemical properties, the metabolic pathway, and the immunogenicity of the iron-carbohydrate complex. As intravenous dextran can cause severe, antibody-mediated dextran-induced anaphylactic reactions (DIAR), the purpose of this study was to explore the potential of various intravenous iron preparations, non-dextran-based or dextran/dextran-based, to induce these reactions. An IgG-isotype mouse monoclonal anti-dextran antibody (5E7H3) and an enzyme-linked immunosorbent assay (ELISA) were developed to investigate the dextran antigenicity of low molecular weight iron dextran, ferumoxytol, iron isomaltoside 1000, ferric gluconate, iron sucrose and ferric carboxymaltose, as well as isomaltoside 1000, the isolated carbohydrate component of iron isomaltoside 1000. Low molecular weight iron dextran, as well as dextran-based ferumoxytol and iron isomaltoside 1000, reacted with 5E7H3, whereas ferric carboxymaltose, iron sucrose, sodium ferric gluconate, and isolated isomaltoside 1000 did not. Consistent results were obtained with reverse single radial immunodiffusion assay. The results strongly support the hypothesis that, while the carbohydrate alone (isomaltoside 1000) does not form immune complexes with anti-dextran antibodies, iron isomaltoside 1000 complex reacts with anti-dextran antibodies by forming multivalent immune complexes. Moreover, non-dextran based preparations, such as iron sucrose and ferric carboxymaltose, do not react with anti-dextran antibodies. This assay allows to assess the theoretical possibility of a substance to induce antibody-mediated DIARs. Nevertheless, as this is only one possible mechanism that may cause a hypersensitivity reaction, a broader set of assays will be required to get an understanding of the mechanisms that may

  13. 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

  14. Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice.

    PubMed

    Jia, Qian; Ivanov, Ivan; Zlatev, Zlatomir Z; Alaniz, Robert C; Weeks, Brad R; Callaway, Evelyn S; Goldsby, Jennifer S; Davidson, Laurie A; Fan, Yang-Yi; Zhou, Lan; Lupton, Joanne R; McMurray, David N; Chapkin, Robert S

    2011-08-01

    Both fish oil (FO) and curcumin have potential as anti-tumour and anti-inflammatory agents. To further explore their combined effects on dextran sodium sulphate (DSS)-induced colitis, C57BL/6 mice were randomised to four diets (2 × 2 design) differing in fatty acid content with or without curcumin supplementation (FO, FO+2 % curcumin, maize oil (control, MO) or MO+2 % curcumin). Mice were exposed to one or two cycles of DSS in the drinking-water to induce either acute or chronic intestinal inflammation, respectively. FO-fed mice exposed to the single-cycle DSS treatment exhibited the highest mortality (40 %, seventeen of forty-three) compared with MO with the lowest mortality (3 %, one of twenty-nine) (P = 0·0008). Addition of curcumin to MO increased (P = 0·003) mortality to 37 % compared with the control. Consistent with animal survival data, following the one- or two-cycle DSS treatment, both dietary FO and curcumin promoted mucosal injury/ulceration compared with MO. In contrast, compared with other diets, combined FO and curcumin feeding enhanced the resolution of chronic inflammation and suppressed (P < 0·05) a key inflammatory mediator, NF-κB, in the colon mucosa. Mucosal microarray analysis revealed that dietary FO, curcumin and FO plus curcumin combination differentially modulated the expression of genes induced by DSS treatment. These results suggest that dietary lipids and curcumin interact to regulate mucosal homeostasis and the resolution of chronic inflammation in the colon.

  15. 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

  16. 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

  17. Sodium Azide Associated Acute Hyperkalemia in a Swine Model of Sodium Azide Toxicity

    DTIC Science & Technology

    2017-06-16

    FROM: 59 MDW/SGVU SUBJECT: Professional Presentation Approval 1. Your paper, entitled Sodium Azide Associated Acute Hvperkalemia in a Swine Model of... Sodium Azide Toxicity presented at/published to SURF, San Antonio, TX, 16 June 2017 in accordance with MDWI 41-108, has been approved and assigned local...34"FROYED On HIS I APPROVED Only] 40. aATE FOR’ n DISN"PRO’.EO TBEREACHED ~a. FRIHTED NA 50. DATE PRE\\ll0 EDIT10NSARE CBSO_ETE Sodium azide associated

  18. Mixed layers of sodium caseinate + dextran sulfate: influence of order of addition to oil-water interface.

    PubMed

    Jourdain, Laureline S; Schmitt, Christophe; Leser, Martin E; Murray, Brent S; Dickinson, Eric

    2009-09-01

    We report on the interfacial properties of electrostatic complexes of protein (sodium caseinate) with a highly sulfated polysaccharide (dextran sulfate). Two routes were investigated for preparation of adsorbed layers at the n-tetradecane-water interface at pH = 6. Bilayers were made by the layer-by-layer deposition technique whereby polysaccharide was added to a previously established protein-stabilized interface. Mixed layers were made by the conventional one-step method in which soluble protein-polysaccharide complexes were adsorbed directly at the interface. Protein + polysaccharide systems gave a slower decay of interfacial tension and stronger dilatational viscoelastic properties than the protein alone, but there was no significant difference in dilatational properties between mixed layers and bilayers. Conversely, shear rheology experiments exhibited significant differences between the two kinds of interfacial layers, with the mixed system giving much stronger interfacial films than the bilayer system, i.e., shear viscosities and moduli at least an order of magnitude higher. The film shear viscoelasticity was further enhanced by acidification of the biopolymer mixture to pH = 2 prior to interface formation. Taken together, these measurements provide insight into the origin of previously reported differences in stability properties of oil-in-water emulsions made by the bilayer and mixed layer approaches. Addition of a proteolytic enzyme (trypsin) to both types of interfaces led to a significant increase in the elastic modulus of the film, suggesting that the enzyme was adsorbed at the interface via complexation with dextran sulfate. Overall, this study has confirmed the potential of shear rheology as a highly sensitive probe of associative electrostatic interactions and interfacial structure in mixed biopolymer layers.

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

    PubMed Central

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

    2017-01-01

    Aim. To investigate the effect of daikenchuto (TJ-100; DKT) for ulcerative colitis (UC) model mouse and assess its anti-inflammatory mechanisms. Methods. We evaluated the effects of DKT on dextran sulfate sodium- (DSS-) induced experimental colitis. First, we assessed the short-term effects of DKT using two groups: 5% DSS group and 5% DSS with DKT group. Colon length; histological scores; and interleukin- (IL-) 10, IL-1β, and tumor necrosis factor-α mRNA expression profiles were analyzed using real-time PCR. Second, we assessed the long-term effects of DKT, by comparing survival time between 2% DSS and 2% DSS with DKT groups. Results. After 7 days, the colon lengths of DSS + DKT group were longer than those of the DSS group (mean values: 6.11 versus 5.69 cm, p < 0.05). Furthermore, compared to DSS group, the DSS + DKT group maintained significantly higher levels of serum hemoglobin (13.1 versus 10.7 g/dL, p < 0.05) and exhibited significantly higher expression levels of IL-10 (p < 0.05). The 2% DSS + DKT group exhibited significantly longer survival time than the 2% DSS group (70 versus 44 days, p < 0.01). Conclusion. Our results indicate that DKT prevented inflammation in the colon, indicating its potential as a new therapeutic agent for UC. PMID:28210268

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

    PubMed

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

    2017-01-01

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

  1. 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

  2. Effects of dietary glutamine on the homeostasis of CD4+ T cells in mice with dextran sulfate sodium-induced acute colitis.

    PubMed

    Hsiung, Yuan-Chin; Liu, Jun-Jen; Hou, Yu-Chen; Yeh, Chiu-Li; Yeh, Sung-Ling

    2014-01-01

    This study investigated the effects of dietary glutamine (Gln) on T-helper (Th) and T regulatory (Treg) cell homeostasis and colonic inflammatory mediator expression in mice with dextran sulfate sodium (DSS)-induced colitis. Mice were randomly assigned to 4 groups with 2 normal control (C and G) and 2 DSS-treated groups (DC and DG). The C and DC groups were fed a common semipurified diet, while the G and DG groups received an identical diet except that part of the casein was replaced by Gln, which provided 25% of the total amino acid nitrogen. Mice were fed the diets for 10 days. On day 6, mice in the normal control groups were given distilled water, while those in the DSS groups were given distilled water containing 1.5% DSS for 5 d. At the end of the experiment, the mice were sacrificed for further examination. Results showed that DC group had higher plasma haptoglobin, colonic weight, immunoglobulin G, inflammatory cytokine and nuclear factor (NF)-κB protein levels. Gln administration lowered inflammatory mediators and NF-κB/IκBα ratio in colitis. Compared with the DC group, the percentages of interleukin-17F and interferon-γ in blood and transcription factors, T-bet and RAR-related orphan receptor-γt, gene expressions in mesenteric lymph nodes were lower, whereas blood Foxp3 was higher in the DG group. Also, DG group had lower colon injury score. These results suggest that Gln administration suppressed Th1/Th17 and Th-associated cytokine expressions and upregulated the expression of Tregs, which may modulate the balance of Th/Treg and reduce inflammatory reactions in DSS-induced colitis.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. Magnolol treatment attenuates dextran sulphate sodium-induced murine experimental colitis by regulating inflammation and mucosal damage.

    PubMed

    Shen, Peng; Zhang, Zecai; He, Yue; Gu, Cong; Zhu, Kunpeng; Li, Shan; Li, Yanxin; Lu, Xiaojie; Liu, Jiuxi; Zhang, Naisheng; Cao, Yongguo

    2018-03-01

    Magnolol, the main and active ingredient of the Magnolia officinalis, has been widely used in traditional prescription to the human disorders. Magnolol has been proved to have several pharmacological properties including anti-bacterial, anti-oxidant and anti-inflammatory activities. However, the effects of magnolol on ulcerative colitis (UC) have not been reported. The aim of this study was to investigate the protective effects and mechanisms of magnolol on dextran sulphate sodium (DSS)-induced colitis in mice. The results showed that magnolol significantly alleviated DSS-induced body weight loss, disease activities index (DAI), colon length shortening and colonic pathological damage. In addition, magnolol restrained the expression of TNF-α, IL-1β and IL-12 via the regulation of nuclear factor-κB (NF-κB) and Peroxisome proliferator-activated receptor-γ (PPAR-γ) pathways. Magnolol also enhanced the expression of ZO-1 and occludin in DSS-induced mice colonic tissues. These results showed that magnolol played protective effects on DSS-induced colitis and may be an alternative therapeutic reagent for colitis treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Dextran Nanoparticle Synthesis and Properties

    PubMed Central

    Wasiak, Iga; Kulikowska, Aleksandra; Janczewska, Magdalena; Michalak, Magdalena; Cymerman, Iwona A.; Nagalski, Andrzej; Kallinger, Peter; Szymanski, Wladyslaw W.; Ciach, Tomasz

    2016-01-01

    Dextran is widely exploited in medical products and as a component of drug-delivering nanoparticles (NPs). Here, we tested whether dextran can serve as the main substrate of NPs and form a stable backbone. We tested dextrans with several molecular masses under several synthesis conditions to optimize NP stability. The analysis of the obtained nanoparticles showed that dextran NPs that were synthesized from 70 kDa dextran with a 5% degree of oxidation of the polysaccharide chain and 50% substitution with dodecylamine formed a NP backbone composed of modified dextran subunits, the mean diameter of which in an aqueous environment was around 100 nm. Dextran NPs could be stored in a dry state and reassembled in water. Moreover, we found that different chemical moieties (e.g., drugs such as doxorubicin) can be attached to the dextran NPs via a pH-dependent bond that allows release of the drug with lowering pH. We conclude that dextran NPs are a promising nano drug carrier. PMID:26752182

  9. Dextran Nanoparticle Synthesis and Properties.

    PubMed

    Wasiak, Iga; Kulikowska, Aleksandra; Janczewska, Magdalena; Michalak, Magdalena; Cymerman, Iwona A; Nagalski, Andrzej; Kallinger, Peter; Szymanski, Wladyslaw W; Ciach, Tomasz

    2016-01-01

    Dextran is widely exploited in medical products and as a component of drug-delivering nanoparticles (NPs). Here, we tested whether dextran can serve as the main substrate of NPs and form a stable backbone. We tested dextrans with several molecular masses under several synthesis conditions to optimize NP stability. The analysis of the obtained nanoparticles showed that dextran NPs that were synthesized from 70 kDa dextran with a 5% degree of oxidation of the polysaccharide chain and 50% substitution with dodecylamine formed a NP backbone composed of modified dextran subunits, the mean diameter of which in an aqueous environment was around 100 nm. Dextran NPs could be stored in a dry state and reassembled in water. Moreover, we found that different chemical moieties (e.g., drugs such as doxorubicin) can be attached to the dextran NPs via a pH-dependent bond that allows release of the drug with lowering pH. We conclude that dextran NPs are a promising nano drug carrier.

  10. The potential mechanism of Bawei Xileisan in the treatment of dextran sulfate sodium-induced ulcerative colitis in mice.

    PubMed

    Wen, Juan; Teng, Baoxia; Yang, Pingrong; Chen, Xinjun; Li, Chenhui; Jing, Yaping; Wei, Junshu; Zhang, Chunjiang

    2016-07-21

    Bawei Xileisan (BXS), a traditional Chinese compound medicine, has been historically used in the treatment of ulcers and inflammation. BXS is also used as a topical agent for the treatment of ulcerative colitis in China. The underlying mechanism, however, remains elusive. Thirty-six female C57BL/6 mice with average weight of 20±2g were used for an in vivo study. The present work was conducted in accordance with the protocols approved by the Ethics Committee of Animal Experiments of Lanzhou University. The mice were induced to develop acute colitis by treating these with 3% dextran sulfate sodium (DSS) solution for 5 days. Subsequently, BXS (200,400mg/kg) was rectally administered daily for one week. All mice were killed at day 12 and their body weight, colon length, and histological changes were all recorded. Serum T helper 17 (Th17) cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). Th17 and regulatory T cell (Treg) in splenocyte mononuclear cells were isolated and identified via flow cytometry. Stool DNA was extracted and the absolute number of Bacteroides and Lactobacillus were measured by using real-time Q-PCR. Shortened colon and damaged tissue structure were profoundly ameliorated by BXS enema. The expression level of Th17-related cytokines IL-17A/F and IL-22 was significantly and dose-dependently reduced, resulting in the restoration of Th17/Treg balance. Moreover, BXS also improved the feces Lactobacillus levels and manifested beneficial effects on Bacteroides. The findings of the present study suggest that BXS is curative in a mouse model of ulcerative colitis, and the underlying mechanism might involve disruption of the Th17 pathway and the induction of a Th17/Treg imbalance, as well as an the development of an opsonic effect on specific gut microbiota. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. Iron Dextran Injection

    MedlinePlus

    Iron dextran injection is used to treat iron-deficiency anemia (a lower than normal number of red blood cells ... treated with iron supplements taken by mouth. Iron dextran injection is in a class of medications called ...

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

    PubMed

    Islam, Jahidul; Koseki, Takuya; Watanabe, Kouichi; Budijanto, Slamet; Oikawa, Akira; Alauddin, Md; Goto, Tomoko; Aso, Hisahi; Komai, Michio; Shirakawa, Hitoshi

    2017-07-13

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

  17. Strawberry Phytochemicals Inhibit Azoxymethane/Dextran Sodium Sulfate-Induced Colorectal Carcinogenesis in Crj: CD-1 Mice

    PubMed Central

    Shi, Ni; Clinton, Steven K.; Liu, Zhihua; Wang, Yongquan; Riedl, Kenneth M.; Schwartz, Steven J.; Zhang, Xiaoli; Pan, Zui; Chen, Tong

    2015-01-01

    Human and experimental colon carcinogenesis are enhanced by a pro-inflammatory microenvironment. Pharmacologically driven chemopreventive agents and dietary variables are hypothesized to have future roles in the prevention of colon cancer by targeting these processes. The current study was designed to determine the ability of dietary lyophilized strawberries to inhibit inflammation-promoted colon carcinogenesis in a preclinical animal model. Mice were given a single i.p. injection of azoxymethane (10 mg kg−1 body weight). One week after injection, mice were administered 2% (w/v) dextran sodium sulfate in drinking water for seven days and then an experimental diet containing chemically characterized lyophilized strawberries for the duration of the bioassay. Mice fed control diet, or experimental diet containing 2.5%, 5.0% or 10.0% strawberries displayed tumor incidence of 100%, 64%, 75% and 44%, respectively (p < 0.05). The mechanistic studies demonstrate that strawberries reduced expression of proinflammatory mediators, suppressed nitrosative stress and decreased phosphorylation of phosphatidylinositol 3-kinase, Akt, extracellular signal-regulated kinase and nuclear factor kappa B. In conclusion, strawberries target proinflammatory mediators and oncogenic signaling for the preventive efficacies against colon carcinogenesis in mice. This works supports future development of fully characterized and precisely controlled functional foods for testing in human clinical trials for this disease. PMID:25763529

  18. 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

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

    PubMed Central

    Matuszyk, Aleksandra; Ceranowicz, Dagmara; Warzecha, Zygmunt; Ceranowicz, Piotr; Fyderek, Krzysztof; Gałązka, Krystyna; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Pihut, Małgorzata; Dembiński, Artur

    2015-01-01

    Ghrelin has protective and therapeutic effects in the gut. The aim of present studies was to investigate the effect of treatment with ghrelin on the development of colitis evoked by dextran sodium sulfate (DSS). Methods. Studies have been performed on rats. Colitis was induced by adding 5% DSS to the drinking water for 5 days. During this period animals were treated intraperitoneally twice a day with saline or ghrelin given at the dose of 8 nmol/kg/dose. On the sixth day, animals were anesthetized and the severity of colitis was assessed. Results. Treatment with ghrelin during administration of DSS reduced the development of colitis. Morphological features of colonic mucosa exhibited a reduction in the area and deep of mucosal damage. Ghrelin reversed the colitis-induced decrease in blood flow, DNA synthesis, and superoxide dismutase activity in colonic mucosa. These effects were accompanied by a decrease in the colitis-evoked increase in mucosal concentration of interleukin-1β and malondialdehyde. Treatment with ghrelin reversed the DSS-induced reduction in body weight gain. Conclusions. Administration of ghrelin exhibits the preventive effect against the development of DSS-induced colitis. This effect seems to be related to ghrelin's anti-inflammatory and antioxidative properties. PMID:26713317

  20. Formulation studies on ibuprofen sodium-cationic dextran conjugate: effect on tableting and dissolution characteristics of ibuprofen.

    PubMed

    Abioye, Amos Olusegun; Kola-Mustapha, Adeola

    2016-01-01

    The effect of electrostatic interaction between ibuprofen sodium (IbS) and cationic diethylaminoethyl dextran (Ddex), on the tableting properties and ibuprofen release from the conjugate tablet was investigated. Ibuprofen exhibits poor flow, compaction (tableting) and dissolution behavior due to its hydrophobic structure, high cohesive, adhesive and viscoelastic properties therefore it was granulated with cationic Ddex to improve its compression and dissolution characteristics. Electrostatic interaction and hydrogen bonding between IbS and Ddex was confirmed with FT-IR and DSC results showed a stepwise endothermic solid-solid structural transformation from racemic to anhydrous forms between 120 and 175 °C which melted into liquid form at 208.15 °C. The broad and diffused DSC peaks of the conjugate granules as well as the disappearance of ibuprofen melting peak provided evidence for their highly amorphous state. It was evident that Ddex improved the flowability and densification of the granules and increased the mechanical and tensile strengths of the resulting tablets as the tensile strength increased from 0.67 ± 0.0172 to 1.90 ± 0.0038 MPa with increasing Ddex concentration. Both tapping and compression processes showed that the most prominent mechanism of densification were particle slippage, rearrangement and plastic deformation while fragmentation was minimized. Ddex retarded the extent of dissolution in general, indicating potentials for controlled release formulations. Multiple release mechanisms including diffusion; anomalous transport and super case II transport were noted. It was concluded that interaction between ibuprofen sodium and Ddex produced a novel formulation with improved flowability, tableting and dissolution characteristics with potential controlled drug release characteristics dictated by Ddex concentration.

  1. Ablation of ceramide synthase 2 exacerbates dextran sodium sulphate-induced colitis in mice due to increased intestinal permeability.

    PubMed

    Kim, Ye-Ryung; Volpert, Giora; Shin, Kyong-Oh; Kim, So-Yeon; Shin, Sun-Hye; Lee, Younghay; Sung, Sun Hee; Lee, Yong-Moon; Ahn, Jung-Hyuck; Pewzner-Jung, Yael; Park, Woo-Jae; Futerman, Anthony H; Park, Joo-Won

    2017-12-01

    Ceramides mediate crucial cellular processes including cell death and inflammation and have recently been implicated in inflammatory bowel disease. Ceramides consist of a sphingoid long-chain base to which fatty acids of various length can be attached. We now investigate the effect of alerting the ceramide acyl chain length on a mouse model of colitis. Ceramide synthase (CerS) 2 null mice, which lack very-long acyl chain ceramides with concomitant increase of long chain bases and C16-ceramides, were more susceptible to dextran sodium sulphate-induced colitis, and their survival rate was markedly decreased compared with that of wild-type littermates. Using mixed bone-marrow chimeric mice, we showed that the host environment is primarily responsible for intestinal barrier dysfunction and increased intestinal permeability. In the colon of CerS2 null mice, the expression of junctional adhesion molecule-A was markedly decreased and the phosphorylation of myosin light chain 2 was increased. In vitro experiments using Caco-2 cells also confirmed an important role of CerS2 in maintaining epithelial barrier function; CerS2-knockdown via CRISPR-Cas9 technology impaired barrier function. In vivo myriocin administration, which normalized long-chain bases and C16-ceramides of the colon of CerS2 null mice, increased intestinal permeability as measured by serum FITC-dextran levels, indicating that altered SLs including deficiency of very-long-chain ceramides are critical for epithelial barrier function. In conclusion, deficiency of CerS2 influences intestinal barrier function and the severity of experimental colitis and may represent a potential mechanism for inflammatory bowel disease pathogenesis. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  2. 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.

  3. Sodium Bicarbonate Versus Sodium Chloride for Preventing Contrast-Associated Acute Kidney Injury in Critically Ill Patients: A Randomized Controlled Trial.

    PubMed

    Valette, Xavier; Desmeulles, Isabelle; Savary, Benoit; Masson, Romain; Seguin, Amélie; Sauneuf, Bertrand; Brunet, Jennifer; Verrier, Pierre; Pottier, Véronique; Orabona, Marie; Samba, Désiré; Viquesnel, Gérald; Lermuzeaux, Mathilde; Hazera, Pascal; Dutheil, Jean-Jacques; Hanouz, Jean-Luc; Parienti, Jean-Jacques; du Cheyron, Damien

    2017-04-01

    To test whether hydration with bicarbonate rather than isotonic sodium chloride reduces the risk of contrast-associated acute kidney injury in critically ill patients. Prospective, double-blind, multicenter, randomized controlled study. Three French ICUs. Critically ill patients with stable renal function (n = 307) who received intravascular contrast media. Hydration with 0.9% sodium chloride or 1.4% sodium bicarbonate administered with the same infusion protocol: 3 mL/kg during 1 hour before and 1 mL/kg/hr during 6 hours after contrast medium exposure. The primary endpoint was the development of contrast-associated acute kidney injury, as defined by the Acute Kidney Injury Network criteria, 72 hours after contrast exposure. Patients randomized to the bicarbonate group (n = 151) showed a higher urinary pH at the end of the infusion than patients randomized to the saline group (n = 156) (6.7 ± 2.1 vs 6.2 ± 1.8, respectively; p < 0.0001). The frequency of contrast-associated acute kidney injury was similar in both groups: 52 patients (33.3%) in the saline group and 53 patients (35.1%) in the bicarbonate group (absolute risk difference, -1.8%; 95% CI [-12.3% to 8.9%]; p = 0.81). The need for renal replacement therapy (five [3.2%] and six [3.9%] patients; p = 0.77), ICU length of stay (24.7 ± 22.9 and 23 ± 23.8 d; p = 0.52), and mortality (25 [16.0%] and 24 [15.9%] patients; p > 0.99) were also similar between the saline and bicarbonate groups, respectively. Except for urinary pH, none of the outcomes differed between the two groups. Among ICU patients with stable renal function, the benefit of using sodium bicarbonate rather than isotonic sodium chloride for preventing contrast-associated acute kidney injury is marginal, if any.

  4. 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.

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

    PubMed Central

    Islam, Jahidul; Koseki, Takuya; Watanabe, Kouichi; Ardiansyah; Budijanto, Slamet; Oikawa, Akira; Alauddin, Md; Goto, Tomoko; Aso, Hisahi; Komai, Michio; Shirakawa, Hitoshi

    2017-01-01

    Rice bran (RB) is a major by-product of rice polishing and a rich source of bioactive compounds. Here, we investigated the anti-colitis effect of diet supplementation with fermented rice bran (FRB) in a murine model of ulcerative colitis. FRB was prepared by dual fermentation of RB using fungi and lactic acid bacteria. Colitis was induced in C57Bl/6N male mice (n = 8/group) by dextran sodium sulfate (DSS). Body weight change, disease activity index (DAI), histopathology score, tissue myeloperoxidase (MPO) activity, cytokine and chemokine transcript levels, and the production of short-chain fatty acids (SCFAs) and mucin in the colonic tissue were monitored. Based on histopathology scores, DSS induced severe mucosal inflammation, with an increased loss of crypts, and inflammatory cell infiltration in the control and RB groups, but not in the FRB group. MPO activity, thiobarbituric acid-reactive substance levels, and pro-inflammatory cytokine transcript (Tnf-α, Il-1β, Il-6, and Il-17) levels were significantly higher in the control and RB groups than in the FRB group. Thus, dietary FRB attenuated intestinal inflammation owing to elevated SCFAs and tryptamine production, which might regulate tight junction barrier integrity and intestinal homeostasis. These results suggest that FRB could comprise an effective potential preventive agent for ulcerative colitis. PMID:28703759

  6. Permeabilization and recovery of the stratum corneum in vivo: the synergy of photomechanical waves and sodium lauryl sulfate.

    PubMed

    Lee, S; McAuliffe, D J; Kollias, N; Flotte, T J; Doukas, A G

    2001-01-01

    Photomechanical waves render the stratum corneum permeable and allow macromolecules to diffuse into the epidermis and dermis. The aim of this study was to investigate the combined action of photomechanical waves and sodium lauryl sulfate, an anionic surfactant, for transdermal delivery. A single photomechanical wave was applied to the skin of rats in the presence of sodium lauryl sulfate. The sodium lauryl sulfate solution was removed and aqueous solutions of rhodamine-B dextran (40 kDa molecular weight) were applied to the skin at time points 2, 30, and 60 minutes post-exposure. The presence of rhodamine-B dextran in the skin was measured by fluorescence emission spectroscopy in vivo and fluorescence microscopy of frozen biopsies. The use of sodium lauryl sulfate delayed the recovery of the stratum corneum barrier and extended the time available for the diffusion of dextran through it. The combination of photomechanical waves and surfactants can enhance transdermal drug delivery. Copyright 2001 Wiley-Liss, Inc.

  7. Single dose oral naproxen and naproxen sodium for acute postoperative pain (Review)

    PubMed Central

    Mason, L; Edwards, JE; Moore, RA; McQuay, HJ

    2014-01-01

    Background Postoperative pain is often poorly managed. Treatment options include a range of drug therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) of which naproxen is one. Naproxen is used to treat a variety of painful conditions including acute postoperative pain, and is often combined with sodium to improve its solubility for oral administration. Naproxen sodium 550 mg (equivalent to 500 mg of naproxen) is considered to be an effective dose for treating postoperative pain but to date no systematic review of the effectiveness of naproxen/naproxen sodium at different doses has been published. Objectives To assess the efficacy, safety and duration of action of a single oral dose of naproxen or naproxen sodium for acute postoperative pain in adults. Search strategy We searched The Cochrane Library, MEDLINE, EMBASE and the Oxford Pain Relief Database for relevant studies. Additional studies were identified from the reference list of retrieved reports. The most recent search was undertaken in July 2004. Selection criteria Included studies were randomised, double blind, placebo-controlled trials of a single dose of orally administered naproxen or naproxen sodium in adults with moderate to severe acute postoperative pain. Data collection and analysis Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50% pain relief over four to six hours. Relative risk estimates (RR) and the number-needed-to-treat (NNT) for at least 50% pain relief were then calculated. Information was sought on the percentage of patients experiencing any adverse event, and the number-needed-to-harm was derived. Time to remedication was also estimated. Main results Ten trials (996 patients) met the inclusion criteria: nine assessed naproxen sodium; one combined the results from two small trials of naproxen alone. Included studies scored well for methodological quality. Meta-analysis of six trials (500

  8. 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.

  9. Acute and Subacute Toxicity of 7.5% Hypertonic Saline/6% Dextran-70 (HSD) in Dogs

    DTIC Science & Technology

    1991-11-18

    7.5% hypertonic saline/6% Dextran-70 in dogs . 1. Serum immunoglobulin and complement responses. J. Appl. Toxicol., in press. 26. G.M. Zaucha, D.F...Dextran-70 (HSD) in Dogs . I PuoiL UM. aucna, DW. Korte, Jr., CE. Wade 13a. TYPE OF REPORT 113b. TIME COVERED 114. DATE OF REPORT (Year, Month, Day) 15...dehydrogenase dogs . 19. ABSTRACT (Continue on reverse if necessary and identify by block number) HSD is currently being evaluated in our laboratory as

  10. Anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium-induced colitis model

    PubMed Central

    Shin, Seung Kak; Cho, Jae Hee; Kim, Eui Joo; Kim, Eun-Kyung; Park, Dong Kyun; Kwon, Kwang An; Chung, Jun-Won; Kim, Kyoung Oh; Kim, Yoon Jae

    2017-01-01

    AIM To evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium (DSS)-induced colitis model. METHODS An acute colitis mouse model was induced by oral administration of 5% DSS in the drinking water for 7 d. In the treated group, rosuvastatin (0.3 mg/kg per day) was administered orally before and after DSS administration for 21 d. On day 21, mice were sacrificed and the colons were removed for macroscopic examination, histology, and Western blot analysis. In the in vitro study, IEC-6 cells were stimulated with 50 ng/mL tumor necrosis factor (TNF)-α and then treated with or without rosuvastatin (2 μmol/L). The levels of reactive oxygen species (ROS), inflammatory mediators, and apoptotic markers were measured. RESULTS In DSS-induced colitis mice, rosuvastatin treatment significantly reduced the disease activity index and histological damage score compared to untreated mice (P < 0.05). Rosuvastatin also attenuated the DSS-induced increase of 8-hydroxy-2’-deoxyguanosine and NADPH oxidase-1 expression in colon tissue. Multiplex ELISA analysis revealed that rosuvastatin treatment reduced the DSS-induced increase of serum IL-2, IL-4, IL-5, IL-6, IL-12 and IL-17, and G-CSF levels. The increased levels of cleaved caspase-3, caspase-7, and poly (ADP-ribose) polymerase in the DSS group were attenuated by rosuvastatin treatment. In vitro, rosuvastatin significantly reduced the production of ROS, inflammatory mediators and apoptotic markers in TNF-α-treated IEC-6 cells (P < 0.05). CONCLUSION Rosuvastatin had the antioxidant, anti-inflammatory and anti-apoptotic effects in DSS-induced colitis model. Therefore, it might be a candidate anti-inflammatory drug in patients with inflammatory bowel disease. PMID:28740344

  11. Nrf2-dependent protection against acute sodium arsenite toxicity in zebrafish

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

    Fuse, Yuji; Nguyen, Vu Thanh; Kobayashi, Makoto, E

    Transcription factor Nrf2 induces a number of detoxifying enzymes and antioxidant proteins to confer protection against the toxic effects of a diverse range of chemicals including inorganic arsenicals. Although a number of studies using cultured cells have demonstrated that Nrf2 has a cell-protective function against acute and high-dose arsenic toxicity, there is no clear in vivo evidence of this effect. In the present study, we genetically investigated the protective role of Nrf2 against acute sodium arsenite toxicity using the zebrafish Nrf2 mutant, nrf2a{sup fh318}. After treatment with 1 mM sodium arsenite, the survival of nrf2a{sup fh318} larvae was significantly shortermore » than that of wild-type siblings, suggesting that Nrf2 protected the zebrafish larvae against high-dose arsenite exposure. To understand the molecular basis of the Nrf2-dependent protection, we analyzed the gene expression profiles after arsenite exposure, and found that the genes involved in the antioxidative function (prdx1 and gclc), arsenic metabolism (gstp1) and xenobiotic elimination (abcc2) were induced in an Nrf2-dependent manner. Furthermore, pre-treatment with sulforaphane, a well-known Nrf2 activator improved the survival of zebrafish larvae after arsenic exposure. Based on these results, we concluded that Nrf2 plays a fundamental and conserved role in protection against acute sodium arsenite toxicity. - Highlights: • The role of Nrf2 under arsenite exposure was valuated using zebrafish. • Nrf2 mutant zebrafish was highly sensitive to acute arsenic toxicity. • Nrf2 induced anti-arsenic genes in response to arsenite. • Sulforaphane attenuated arsenic toxicity through Nrf2 activation. • Nrf2 system plays an important role in the defense against acute arsenic toxicity.« less

  12. 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

  13. 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

  14. Boswellia serrata resin extract alleviates azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumorigenesis.

    PubMed

    Chou, Ya-Chun; Suh, Joon Hyuk; Wang, Yu; Pahwa, Manoj; Badmaev, Vladimir; Ho, Chi-Tang; Pan, Min-Hsiung

    2017-09-01

    Boswellia serrata (BS) resin is a popular dietary supplement for joint nourishment. In this study, we investigated the chemopreventive effects of dietary BS extract and its impact of gut microbiota on azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated colon cancer in mice. Male ICR mice were injected with AOM and 2% DSS via drinking water. The mice were fed with 0.25 or 0.5% BS extract, and colonic tissue were collected at 15 weeks. The main effective components of BS supercritical CO 2 extraction were analyzed by LC-MS/MS are boswellic acids. We found that treatment with BS extract significantly reduce the colonic tumor formation. Western blot and histological analysis revealed that dietary BS extract could markedly reduce the inflammation associated protein levels expression. Furthermore, BS extract reduced cell proliferation via inhibiting phosphorylation level of protein kinase B (Akt), glycogen synthase kinase 3β (GSK3β), and downregulation of cyclin D1. In addition, BS extract also altered the composition of gut microbiota by enhancing the proportion of Clostridiales and reducing the percentage of Bacteroidales. In summary, BS extract decreased the protein levels of inflammative enzymes such as inducible nitric oxide synthase and cyclooxygenase-2 in colonic mucosa. It also mediated Akt/GSK3β/cyclin D1 signaling pathway and altered the composition of gut microbiota to alleviate tumor growth. Taken together, this study suggests that BS extract has great potential to suppress colon tumorigenesis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Methyl-DEAE-dextran: a candidate biomaterial.

    PubMed

    Zambito, Ylenia; Baggiani, Andrea; Carelli, Vera; Serafini, Maria Francesca; Di Colo, Giacomo

    2004-01-01

    The full quaternisation of DEAE-dextran was successfully attempted and an application of the quaternised product was suggested. Commercial DEAE-dextran was reacted with iodomethane at 60 degrees C in the presence of NaOH. The raw product was purified by dialysis, during which the iodide ion was replaced by chloride. N-methylation and O-methylation resulted from the reaction. A second methylation step produced no further changes in the molecule. Alkalimetry indicated the absence of amino groups in the methylated polymer molecule, thus testifying to a complete quaternisation. N-acetylcysteine (AcCy) was neutralised with the polymer in the hydroxide form, thus obtaining the methyl DEAE-dextran salt of AcCy (Me-DEAE-dextran/AcCy), whereby an ophthalmic formulation for the treatment of the dry eye syndrome was prepared. For comparison, the neutral AcCy salt of commercial DEAE-dextran (DEAE-dextran/AcCy) was prepared. The AcCy content in Me-DEAE-dextran/AcCy was higher than in DEAE-dextran/AcCy (23 vs 13%), while the viscosity of a solution containing the salt concentration corresponding to the therapeutic AcCy concentration (4%w/v) was lower with the former compared to the latter salt (20.5 vs 23.9 mPa s). Both solutions were ipotonic (245 mOsm/kg), whereas the commercial Tirocular is strongly hypertonic (900 mOsm/kg) and irritant.

  16. Pharmacological activity of 6-gingerol in dextran sulphate sodium-induced ulcerative colitis in BALB/c mice.

    PubMed

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

    2015-04-01

    Gingerols are phenolic compounds in ginger (Zingiber officinale), which have been reported to exhibit antiinflammatory, antioxidant, and anticancer properties. The present study aimed at evaluating the possible pharmacologic activity of 6-gingerol in a mouse model of dextran sulphate sodium (DSS)-induced ulcerative colitis. Adult male mice were exposed to DSS in drinking water alone or co-treated with 6-gingerol orally at 50, 100, and 200 mg/kg for 7 days. Disease activity index, inflammatory mediators, oxidative stress indices, and histopathological examination of the colons were evaluated to monitor treatment-related effects of 6-gingerol in DSS-treated mice. Administration of 6-gingerol significantly reversed the DSS-mediated reduction in body weight, diarrhea, rectal bleeding, and colon shrinkage to near normal. Moreover, 6-gingerol significantly suppressed the circulating concentrations of interleukin-1β and tumor necrosis factor alpha and restored the colonic nitric oxide concentration and myeloperoxidase activity to normal in DSS-treated mice. 6-Gingerol efficiently prevented colonic oxidative damage by increasing the activities of antioxidant enzymes and glutathione content, decreasing the hydrogen peroxide and malondialdehyde levels, and ameliorated the colonic atrophy in DSS-treated mice. 6-Gingerol suppressed the induction of ulcerative colitis in mice via antioxidant and antiinflammatory activities, and may thus represent a potential anticolitis drug candidate. Copyright © 2015 John Wiley & Sons, Ltd.

  17. 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

  18. Repeated dose 28-day oral toxicity study of DEAE-Dextran in mice: An advancement in safety chemotherapeutics.

    PubMed

    Bakrania, Anita K; Variya, Bhavesh C; Madan, Prem; Patel, Snehal S

    2017-08-01

    Cancer has emerged as a global threat with challenges for safe chemotherapeutics. Most of the currently available anti-cancer drugs exhibit significant toxicity. Amongst novel agents, interferons have exhibited anti-proliferative and cytoprotective roles. However, due to stability drawbacks of interferons, we have identified an interferon inducer DEAE-Dextran, which resolves the stability issues. Based on the previous history of toxicity pertaining to the current chemotherapeutic agents, it is equally essential to determine the safety of DEAE-Dextran. In the present study, repeated dose 28 day oral toxicity of DEAE-Dextran has been evaluated in accordance to OECD-407. We found absence of any CNS behavioral changes related to self-mutilation, walking backwards, aggressiveness on handling or tonic-clonic seizures during the 28 day study. Neither the motor activity nor grip strength was altered during the treatment duration with DEAE-Dextran implying absence of any effect on the skeletal muscles. Interestingly, we also found that treatment with DEAE-Dextran did not present any significant cardiac, hepatic, renal, gastrointestinal, lymphatic or reproductive system toxicity or alteration in the body's normal physiology based upon the various organ function tests. Henceforth, it may be concluded that DEAE-Dextran is a safe anti-cancer agent devoid of any sub-acute toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Radiation cross-linked collagen/dextran dermal scaffolds: effects of dextran on cross-linking and degradation.

    PubMed

    Zhang, Yaqing; Zhang, Xiangmei; Xu, Ling; Wei, Shicheng; Zhai, Maolin

    2015-01-01

    Ionizing radiation effectively cross-links collagen into network with enhanced anti-degradability and biocompatibility, while radiation-cross-linked collagen scaffold lacks flexibility, satisfactory surface appearance, and performs poor in cell penetration and ingrowth. To make the radiation-cross-linked collagen scaffold to serve as an ideal artificial dermis, dextran was incorporated into collagen. Scaffolds with the collagen/dextran (Col/Dex) ratios of 10/0, 7/3, and 5/5 were fabricated via (60)Co γ-irradiation cross-linking, followed by lyophilization. The morphology, microstructure, physicochemical, and biological properties were investigated. Compared with pure collagen, scaffolds with dextran demonstrated more porous appearance, enhanced hydrophilicity while the cross-linking density was lower with the consequence of larger pore size, higher water uptake, as well as reduced stiffness. Accelerated degradation was observed when dextran was incorporated in both the in vitro and in vivo assays, which led to earlier integration with cell and host tissue. The effect of dextran on degradation was ascribed to the decreased cross-linking density, looser microstructure, more porous and hydrophilic surface. Considering the better appearance, softness, moderate degradation rate due to controllable cross-linking degree and good biocompatibility as well, radiation-cross-linked collagen/dextran scaffolds are expected to serve as promising artificial dermal substitutes.

  20. Clevidipine as a therapeutic and cost-effective alternative to sodium nitroprusside in patients with acute aortic syndromes.

    PubMed

    Alviar, Carlos L; Gutierrez, Alejandra; Cho, Leslie; Krishnaswamy, Amar; Saleh, Amr; Lincoff, Michael A; Roselli, Eric; Militello, Michael; Menon, Venu

    2018-06-01

    Sodium nitroprusside is the preferred agent for the treatment of high blood pressure during acute aortic syndrome if blood pressure remains elevated after heart rate control with beta-blockers. The increasing cost of sodium nitroprusside in the USA led us to assess the efficacy and safety of intravenous clevidipine, a calcium channel blocker with quick onset of action, short half-life and significantly lower costs than sodium nitroprusside, in patients presenting with acute aortic syndrome. We performed a retrospective chart review of consecutive patients admitted to the Cleveland Clinic Cardiac Intensive Care Unit from 2013-2016 with a diagnosis of acute aortic syndrome. Patients who received intravenous sodium nitroprusside were compared with those receiving intravenous clevidipine. The primary outcome was a significant difference in blood pressure at one, three and six hours. Secondary outcomes included time to achieving blood pressure target and in hospital mortality with rates of hypotension and bradycardia as safety endpoints. A total of 85 patients with suspected acute aortic pathology received clevidipine and 50 received sodium nitroprusside. Clinical and demographic characteristics were similar in both groups, except for a higher incidence of abdominal aortic aneurysm in the clevidipine group and for a trend towards higher use of labetalol in the clevidipine group. There were no significant differences in blood pressure or heart rate at one, three and six hours after starting either infusion. The rates of hypotension, bradycardia and in-hospital mortality did not differ. Time to achieve blood pressure control were also similar between groups. Intravenous clevidipine appears to be a safe and effective alternative to sodium nitroprusside for the management of high blood pressure during acute aortic dissection. In the USA, clevidipine could represent a cost effective therapy providing similar outcomes than sodium nitroprusside.

  1. Effect of dextran-70 on outcome in severe sepsis; a propensity-score matching study.

    PubMed

    Bentzer, Peter; Broman, Marcus; Kander, Thomas

    2017-07-06

    Albumin may be beneficial in patients with septic shock but availability is limited and cost is high. The objective of the present study was to investigate if the use of dextran-70 in addition to albumin and crystalloids influences organ failure or mortality in patients with severe sepsis or septic shock. Patients with severe sepsis or septic shock (n = 778) admitted to a university hospital intensive care unit (ICU) between 2007 and 2015 that received dextran-70 during resuscitation were propensity score matched to controls at a 1 to 1 ratio. Outcomes were highest acute kidney injury network (AKIN) score the first 10 days in the ICU, use of renal replacement therapy, days alive and free of organ support the first 28 days after admission to ICU, mortality and events of severe bleeding. Outcomes were assessed using paired hypothesis testing. Propensity score matching resulted in two groups of patients with 245 patients in each group. The dextran group received a median volume of 1483 ml (interquartile range, 1000-2000 ml) of dextran-70 during the ICU stay. Highest AKIN score did not differ between the control- and dextran groups (1 (0-3) versus 2 (0-3), p = 0.06). Incidence of renal replacement therapy in the control- and dextran groups was similar (19% versus 22%, p = 0.42, absolute risk reduction -2.9% [95% CI: -9.9 to 4.2]). Days alive and free of renal replacement, vasopressors and mechanical ventilation did not differ between the control- and dextran groups. The 180-day mortality was 50.2% in the control group and 41.6% in the dextran group (p = 0.046, absolute risk reduction 8.6% [-0.2 to 17.4]). Fraction of patients experiencing a severe bleeding in the first 10 days in the ICU did not differ between the control and dextran groups (14% versus 18%, p = 0.21). There is a paucity of high quality data regarding effects of dextran solutions on outcome in sepsis. In the present study, propensity score matching was used in attempt to reduce bias. No

  2. Serum sodium concentration, blood urea nitrogen, and outcomes in patients hospitalized for acute decompensated heart failure.

    PubMed

    Kajimoto, Katsuya; Minami, Yuichiro; Sato, Naoki; Takano, Teruo

    2016-11-01

    This study investigated the association of a low serum sodium and elevated blood urea nitrogen (BUN) with outcomes in acute decompensated heart failure (HF) patients. Of the 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4438 patients discharged after hospitalization for acute decompensated HF were investigated to assess the association of a low serum sodium and/or elevated BUN at discharge with all-cause mortality. The patients were divided into four groups based on serum sodium (>136 or ≤136mEq/l) and BUN (<25 or ≥25mg/dl) at discharge. The median follow-up period after discharge was 517 (381-776) days. According to multivariate analysis, a low serum sodium (≤136mEq/l) or an elevated BUN (≥25mg/dl) was significantly associated with a higher risk of all-cause death compared with patients who had neither (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.22 to 1.94; P<0.001 and HR, 1.44; 95% CI, 1.19 to 1.73; P<0.001, respectively). Patients with both low serum sodium and elevated BUN had a higher risk of all-cause death relative to patients with neither (HR, 2.64; 95% CI, 2.17 to 3.20; P<0.001) and also relative to patients with either low serum sodium alone or elevated BUN alone (HR, 1.72; 95% CI, 1.36 to 2.18; P<0.001 and HR, 1.84; 95% CI, 1.53 to 2.21; P<0.001, respectively). These findings demonstrated that a low serum sodium and an elevated BUN may be additive risk factors for postdischarge mortality in acute decompensated HF patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Indigo Naturalis ameliorates murine dextran sodium sulfate-induced colitis via aryl hydrocarbon receptor activation.

    PubMed

    Kawai, Shoichiro; Iijima, Hideki; Shinzaki, Shinichiro; Hiyama, Satoshi; Yamaguchi, Toshio; Araki, Manabu; Iwatani, Shuko; Shiraishi, Eri; Mukai, Akira; Inoue, Takahiro; Hayashi, Yoshito; Tsujii, Masahiko; Motooka, Daisuke; Nakamura, Shota; Iida, Tetsuya; Takehara, Tetsuo

    2017-08-01

    Indigo Naturalis (IN) is used as a traditional herbal medicine for ulcerative colitis (UC). However, the mechanisms of action of IN have not been clarified. We aimed to evaluate the efficacy of IN for ameliorating colonic inflammation. We further investigated the mechanisms of action of IN. Colitis severity was assessed in dextran sodium sulfate-induced colitis and trinitrobenzene sulfonic acid-induced colitis models with or without the oral administration of IN or indigo, which is a known major component of IN. Colonic lamina propria (LP) mononuclear cells isolated from IN-treated mice were analyzed with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry. LP and splenic mononuclear cells cultured in vitro with IN or indigo were also analyzed. The role of the candidate receptor for indigo, the aryl hydrocarbon receptor (AhR), was analyzed using Ahr-deficient mice. Colitis severity was significantly ameliorated in the IN and indigo treatment groups compared with the control group. The mRNA expression levels of interleukin (Il)-10 and Il-22 in the LP lymphocytes were increased by IN treatment. The treatment of splenocytes with IN or indigo increased the expression of anti-inflammatory cytokines and resulted in the expansion of IL-10-producing CD4 + T cells and IL-22-producing CD3 - RORγt + cells, but not CD4 + Foxp3 + regulatory T cells. The amelioration of colitis by IN or indigo was abrogated in Ahr-deficient mice, in association with diminished regulatory cytokine production. IN and indigo ameliorated murine colitis through AhR signaling activation, suggesting that AhR could be a promising therapeutic target for UC.

  4. Transfection using DEAE-dextran.

    PubMed

    Gulick, T

    2001-05-01

    Transfection of cultured mammalian cells using diethylaminoethyl (DEAE)-dextran/DNA can be an attractive alternative to other transfection methods in many circumstances. The major advantages of the technique are its relative simplicity and speed, limited expense, and remarkably reproducible interexperimental and intraexperimental transfection efficiency. Disadvantages include inhibition of cell growth and induction of heterogeneous morphological changes in cells. Furthermore, the concentration of serum in the culture medium must be transiently reduced during the transfection. In general, DEAE-dextran DNA transfection is ideal for transient transfections with promoter/reporter plasmids in analyses of promoter and enhancer functions, and is suitable for overexpression of recombinant protein in transient transfections or for generation of stable cell lines using vectors designed to exist in the cell as episomes. This unit presents a general description of DEAE-dextran transfection, as well as two more specific protocols for typical experimental applications. The basic protocol is suitable for transfection of anchorage-dependent (attached) cells. For cells that grow in suspension, electroporation or lipofection is usually preferred, although DEAE-dextran-mediated transfection can be used.

  5. Transfection using DEAE-dextran.

    PubMed

    Gulick, Tod

    2003-08-01

    Transfection of cultured mammalian cells using diethylaminoethyl (DEAE)-dextran/DNA can be an attractive alternative to other transfection methods in many circumstances. The major advantages of the technique are its relative simplicity and speed, limited expense, and remarkably reproducible interexperimental and intraexperimental transfection efficiency. Disadvantages include inhibition of cell growth and induction of heterogeneous morphological changes in cells. Furthermore, the concentration of serum in the culture medium must be transiently reduced during the transfection. In general, DEAE-dextran DNA transfection is ideal for transient transfections with promoter/reporter plasmids in analyses of promoter and enhancer functions, and is suitable for overexpression of recombinant protein in transient transfections or for generation of stable cell lines using vectors designed to exist in the cell as episomes. This unit presents a general description of DEAE-dextran transfection, as well as two more specific protocols for typical experimental applications. The basic protocol is suitable for transfection of anchorage-dependent (attached) cells. For cells that grow in suspension, electroporation or lipofection is usually preferred, although DEAE-dextran-mediated transfection can be used.

  6. Transfection using DEAE-dextran.

    PubMed

    Gulick, T

    2001-05-01

    Transfection of cultured mammalian cells using diethylaminoethyl (DEAE)-dextran/DNA can be an attractive alternative to other transfection methods in many circumstances. The major advantages of the technique are its relative simplicity and speed, limited expense, and remarkably reproducible interexperimental and intraexperimental transfection efficiency. Disadvantages include inhibition of cell growth and induction of heterogeneous morphological changes in cells. Furthermore, the concentration of serum in the culture medium must be transiently reduced during the transfection. In general, DEAE-dextran DNA transfection is ideal for transient transfections with promoter/reporter plasmids in analyses of promoter and enhancer functions, and is suitable for overexpression of recombinant protein in transient transfections or for generation of stable cell lines using vectors designed to exist in the cell as episomes. This unit presents a general description of DEAE-dextran transfection, as well as two more specific protocols for typical experimental applications. The Basic Protocol is suitable for transfection of anchorage-dependent (attached) cells. For cells that grow in suspension, electroporation or lipofection is usually preferred, although DEAE-dextran-mediated transfection can be used.

  7. Dextran-encapsulated photoluminescent gold nanoclusters: synthesis and application

    NASA Astrophysics Data System (ADS)

    Chiu, Wei-Ju; Chen, Wei-Yu; Lai, Hong-Zheng; Wu, Ching-Yi; Chiang, Hsiang-Lin; Chen, Yu-Chie

    2014-07-01

    Dextrans are widely used as additives in food, pharmaceutical, and cosmetics because of their hydrophilicity, biocompatibility, and low toxicity. These features allow the use of dextrans to modify the surface of nanoparticles to improve cell compatibility for biomedical applications. Additionally, dextran molecules covalently bound with fluorescent dyes are frequently used as tracers in animal studies. These facts show that dextrans are useful compounds for biomedicine-related applications and research. Our aim was to explore a facile way to generate dextran-derived nanoparticles with photoluminescent property for the use in fluorescence imaging of bacteria and cancer cells. Dextran-encapsulated gold nanoclusters (AuNCs@dextran) were generated through a one-pot reaction by stirring dextrans and aqueous tetrachloroauric acid overnight. The generated AuNCs exhibit bright and green photoluminescence under the illumination of an ultraviolet lamp ( λ max = 365 nm), and high cell biocompatibility was found as well. Therefore, the generated AuNCs can be used as fluorescence tracers and nanoprobes. We explored the suitability of AuNCs@dextran as labeling agents for bacteria, such as Staphylococcus aureus and Escherichia coli. After the bacteria were labeled by AuNCs@dextran, they became quite visible under a fluorescence microscope. Additionally, we demonstrated that nanocomposites composed of AuNCs@dextran and silica beads can be readily internalized by cancer cells. The nanocomposites can be readily detected in the cells through their photoluminescence, suggesting possible applications in drug delivery and fluorescence imaging.

  8. 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-1

  9. 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-1

  10. Effects of arachidonic acid intake on inflammatory reactions in dextran sodium sulphate-induced colitis in rats.

    PubMed

    Naito, Yukiko; Ji, Xu; Tachibana, Shigehiro; Aoki, Satoko; Furuya, Mami; Tazura, Yoshiyuki; Miyazawa, Daisuke; Harauma, Akiko; Moriguchi, Toru; Nagata, Tomoko; Iwai, Naoharu; Ohara, Naoki

    2015-09-14

    The aim of this study was to investigate the effects of the administration of oral arachidonic acid (AA) in rats with or without dextran sulphate sodium (DSS)-induced inflammatory bowel disease. Male Wistar rats were administered AA at 0, 5, 35 or 240 mg/kg daily by gavage for 8 weeks. Inflammatory bowel disease was induced by replacing drinking water with 3 % DSS solution during the last 7 d of the AA dosing period. These animals passed loose stools, diarrhoea and red-stained faeces. Cyclo-oxygenase-2 concentration and myeloperoxidase activity in the colonic tissue were significantly increased in the animals given AA at 240 mg/kg compared with the animals given AA at 0 mg/kg. Thromboxane B2 concentration in the medium of cultured colonic mucosae isolated from these groups was found to be dose-dependently increased by AA, and the increase was significant at 35 and 240 mg/kg. Leukotriene B4 concentration was also significantly increased and saturated at 5 mg/kg. In addition, AA at 240 mg/kg promoted DSS-induced colonic mucosal oedema with macrophage infiltration. In contrast, administration of AA for 8 weeks, even at 240 mg/kg, showed no effects on the normal rats. These results suggest that in rats with bowel disease AA metabolism is affected by oral AA, even at 5 mg/kg per d, and that excessive AA may aggravate inflammation, whereas AA shows no effects in rats without inflammatory bowel disease.

  11. Impact of dextran sulphate sodium-induced colitis on the intestinal transport of the colon carcinogen PhIP.

    PubMed

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

    2016-05-01

    Colorectal cancer is one of the most frequent cancers in Western countries. Chronic intestinal diseases such as Crohn's disease and ulcerative colitis, in which the intestinal barrier is massively disturbed, significantly raise the risk of developing a colorectal tumour. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a genotoxic heterocyclic aromatic amine that is formed after strongly heating fish and meat. In this study, the hypothesis that PhIP uptake in the gut is increased during chronic colitis was tested. Chronic colitis was induced by oral administration of dextran sulphate sodium (DSS) to Fischer 344 rats. The transport of PhIP in eight different rat intestinal segments was examined in Ussing chambers. The tissues were incubated with 10 µM PhIP for 90 min, and the concentration of PhIP was determined in the mucosal and serosal compartments of the Ussing chambers as well as in the clamped tissues by LC-MS. Although chronic colitis was clearly induced in the rats, no differences in the intestinal transport of PhIP were observed between control and DSS-treated animals. The hypothesis that in the course of chronic colitis more PhIP is taken up by the intestinal epithelium, thereby increasing the risk of developing colorectal cancer, could not be confirmed in the present report.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-14

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

  14. Dextransucrase and the mechanism for dextran biosynthesis.

    PubMed

    Robyt, John F; Yoon, Seung-Heon; Mukerjea, Rupendra

    2008-12-08

    Remaud-Simeon and co-workers [Moulis, C.; Joucla, G.; Harrison, D.; Fabre, E.; Potocki-Veronese, G.; Monsan, P.; Remaud-Simeon, M. J. Biol. Chem., 2006, 281, 31254-31267] have recently proposed that a truncated Escherichia coli recombinant B-512F dextransucrase uses sucrose and the hydrolysis product of sucrose, D-glucose, as initiator primers for the nonreducing-end synthesis of dextran. Using (14)C-labeled D-glucose in a dextransucrase-sucrose digest, it was found that <0.02% of the D-glucose appears in a dextran of M(n) 84,420, showing that D-glucose is not an initiator primer, and when the dextran was treated with 0.01 M HCl at 80 degrees C for 90 min and a separate sample with invertase at 50 degrees C for 24h, no D-fructose was formed, indicating that sucrose is not present at the reducing-end of dextran, showing that sucrose also was not an initiator primer. It is further shown that both d-glucose and dextran are covalently attached to B-512FMC dextransucrase at the active site during polymerization. A pulse reaction with [(14)C]-sucrose and a chase reaction with nonlabeled sucrose, followed by dextran isolation, reduction, and acid hydrolysis, gave (14)C-glucitol in the pulsed dextran, which was significantly decreased in the chased dextran, showing that the D-glucose moieties of sucrose are added to the reducing-ends of the covalently linked growing dextran chains. The molecular size of dextran is shown to be inversely proportional to the concentration of the enzyme, indicating a highly processive mechanism in which D-glucose is rapidly added to the reducing-ends of the growing chains, which are extruded from the active site of dextransucrase. It is also shown how the three conserved amino acids (Asp551, Glu589, and Asp 622) at the active sites of glucansucrases participate in the polymerization of dextran and related glucans from a single active site by the addition of the D-glucose moiety of sucrose to the reducing-ends of the covalently linked glucan

  15. Dextran sodium sulphate-induced colitis perturbs muscarinic cholinergic control of colonic epithelial ion transport

    PubMed Central

    Sayer, Brooke; Lu, Jun; Green, Christina; Söderholm, Johan D; Akhtar, Mahmood; McKay, Derek M

    2002-01-01

    Neuronal cholinergic input is an important regulator of epithelial electrolyte transport and hence water movement in the gut. In this study, colitis was induced by treating mice with 4% (w v−1) dextran sodium-sulphate (DSS)-water for 5 days followed by 3 days of normal water. Mid-colonic segments were mounted in Ussing chambers and short-circuit current (Isc, indicates net ion movement) responses to the cholinergic agonist, carbachol (CCh; 10−4 M)±tetrodotoxin, atropine (ATR), hexamethonium (HEX), naloxone or phenoxybenzamine were assessed. Tissues from mice with DSS-induced colitis displayed a drop in Isc in response to CCh (−11.3±3.3 μA/cm2), while those from control mice showed a transient increase in Isc (76.3±13.0 μA/cm2). The ΔIsc in colon from DSS-treated mice was tetrodotoxin-sensitive, atropine-insensitive and was reversed by hexamethonium (HEX+CCh=16.7±7.8 μA/cm2), indicating involvement of a nicotinic receptor. CCh induced a drop in Isc in tissues from controls only when they were pretreated with the cholinergic muscarinic receptor blocker, atropine: ATR+CCh=−21.3±7.0 μA/cm2. Nicotine elicited a drop in Isc in Ussing-chambered colon from both control and DSS-treated mice that was TTX-sensitive. The drop in Isc evoked by CCh challenge of colonic tissue from DSS-treated mice or ATR+CCh challenge of control tissue was not significantly affected by blockade of opiate or α-adrenergic receptors by naloxone or phenoxybenzamine, respectively. The data indicate that DSS-colitis reveals a nicotinic receptor that becomes important in cholinergic regulation of ion transport. PMID:11934821

  16. Dietary black raspberries modulate DNA methylation in dextran sodium sulfate (DSS)-induced ulcerative colitis

    PubMed Central

    Wang, Li-Shu

    2013-01-01

    Ulcerative colitis (UC) is characterized by chronic inflammation of the colon. During inflammation, NF-κB is increased in colonic epithelial cells and in immune cells, leading to increases in proinflammatory cytokines. These events then increase DNA methyltransferases (DNMTs), which silence a subset of tumor suppressor genes by promoter methylation. Negative regulators of the Wnt pathway are frequently methylated in UC, leading to dysregulation of the pathway and, potentially, to colorectal cancer. We determined if black raspberries (BRBs) influence promoter methylation of suppressors in the Wnt pathway in dextran sodium sulfate (DSS)-induced UC. C57BL/6J mice received 1% DSS and were fed either control or 5% BRB diets. Mice were euthanized on days 7, 14 and 28, and their colons, spleen and bone marrow were collected. Berries reduced ulceration at day 28. This was accompanied by decreased staining of macrophages and neutrophils and decreased NF-κB p65 nuclear localization in the colon at all time points. At day 7, BRBs demethylated the promoter of dkk3, leading to its increased messenger RNA (mRNA) expression in colon, spleen and bone marrow. β-Catenin nuclear localization, c-Myc staining as well as protein expression of DNMT3B, histone deacetylases 1 and 2 (HDAC1 and HDAC2) and methyl-binding domain 2 (MBD2) were all decreased in colon; mRNA expression of these four proteins was decreased in bone marrow cells by BRBs. These results suggest that BRBs suppress colonic ulceration by correcting promoter hypermethylation of suppressor genes in the colon, as well as in the spleen and bone marrow that systematically regulate inflammation. Summary: Our results suggest that dietary BRBs suppress colonic ulceration by correcting promoter hypermethylation of suppressor genes in the colon, as well as in the spleen and bone marrow that systematically regulate inflammation in DSS-induced UC. PMID:24067901

  17. 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.

  18. Epidermal growth factor receptor is required for colonic tumor promotion by dietary fat in the azoxymethane/dextran sulfate sodium model: roles of transforming growth factor-{alpha} and PTGS2.

    PubMed

    Dougherty, Urszula; Cerasi, Dario; Taylor, Ieva; Kocherginsky, Masha; Tekin, Ummuhan; Badal, Shamiram; Aluri, Lata; Sehdev, Amikar; Cerda, Sonia; Mustafi, Reba; Delgado, Jorge; Joseph, Loren; Zhu, Hongyan; Hart, John; Threadgill, David; Fichera, Alessandro; Bissonnette, Marc

    2009-11-15

    Colon cancer is a major cause of cancer deaths. Dietary factors contribute substantially to the risk of this malignancy. Western-style diets promote development of azoxymethane-induced colon cancer. Although we showed that epidermal growth factor receptors (EGFR) controlled azoxymethane tumorigenesis in standard fat conditions, the role of EGFR in tumor promotion by high dietary fat has not been examined. A/J x C57BL6/J mice with wild-type Egfr (Egfr(wt)) or loss-of-function waved-2 Egfr (Egfr(wa2)) received azoxymethane followed by standard (5% fat) or western-style (20% fat) diet. As F(1) mice were resistant to azoxymethane, we treated mice with azoxymethane followed by one cycle of inflammation-inducing dextran sulfate sodium to induce tumorigenesis. Mice were sacrificed 12 weeks after dextran sulfate sodium. Tumors were graded for histology and assessed for EGFR ligands and proto-oncogenes by immunostaining, Western blotting, and real-time PCR. Egfr(wt) mice gained significantly more weight and had exaggerated insulin resistance compared with Egfr(wa2) mice on high-fat diet. Dietary fat promoted tumor incidence (71.2% versus 36.7%; P < 0.05) and cancer incidence (43.9% versus 16.7%; P < 0.05) only in Egfr(wt) mice. The lipid-rich diet also significantly increased tumor and cancer multiplicity only in Egfr(wt) mice. In tumors, dietary fat and Egfr(wt) upregulated transforming growth factor-alpha, amphiregulin, CTNNB1, MYC, and CCND1, whereas PTGS2 was only increased in Egfr(wt) mice and further upregulated by dietary fat. Notably, dietary fat increased transforming growth factor-alpha in normal colon. EGFR is required for dietary fat-induced weight gain and tumor promotion. EGFR-dependent increases in receptor ligands and PTGS2 likely drive diet-related tumor promotion.

  19. Intravenous Sodium Valproate for Acute Pediatric Headache.

    PubMed

    Sheridan, David; Sun, Benjamin; O'Brien, Patricia; Hansen, Matthew

    2015-10-01

    Headaches are common in the pediatric population, and increase in prevalence with age. The abortive medications currently used have a number of potential side effects. Sodium valproate (VPA) has been shown to be effective for acute treatment in the adult population, but no data exist in the pediatric population. The objective of this study was to evaluate the effectiveness of VPA for acute pediatric headache in the emergency department. This was a retrospective case series of all patients <19 years of age treated in the pediatric emergency department (PED) at two tertiary care pediatric hospitals and with a final diagnosis of migraine or headache who received parenteral VPA. Data collected included patient demographics, pain reduction, length of stay, and final disposition. From July 2010 to February 2014, there were 16 patients who received VPA for acute headache in the PED; 4 were excluded. Eighty-three percent were discharged home. Mean length of stay in the PED before VPA was 395 min, and 120 min after VPA administration. Patients achieved a 17% mean pain score reduction before VPA and approximately an additional 40% mean pain reduction after VPA infusion. VPA appears to be an effective agent for acute pediatric headache in this small series. Patients responded well to VPA in a relatively short amount of time. Further studies are needed to evaluate its effectiveness in combination with other first-line medications or as a single agent. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Molecular recognition between insulin and dextran encapsulated gold nanoparticles.

    PubMed

    Lee, Kai-Chieh; Chiang, Hsiang-Ling; Chiu, Wei-Ru; Chen, Yu-Chie

    2016-11-01

    Insulin is a peptide hormone that can regulate the metabolism of carbohydrates and lipids. This hormone is closely related to glucose-uptake in cells and can control blood glucose levels. Dextran is a polysaccharide composed of glucose units. In this study, we discovered that dextran-encapsulated gold nanoparticles (AuNPs@Dextran) and nanoclusters (AuNCs@Dextran) can be used to recognize insulin. The dissociation constant of insulin toward AuNPs@Dextran was estimated to be ∼5.3 × 10 -6  M. The binding site on insulin toward the dextran on the nanoprobes was explored as well. It was found that the sequence of numbers 1-22 on the insulin B chain can interact with the dextran encapsulated nanoprobes. Additionally, we also demonstrated that the dextran-encapsulated nanoprobes could be used as concentration probes to selectively enrich trace amounts of insulin (∼1 pM) from serum samples. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Periodate oxidation of nanoscaled magnetic dextran composites

    NASA Astrophysics Data System (ADS)

    Hong, Xia; Guo, Wei; Yuan, Hang; Li, Jun; Liu, Yanmei; Ma, Lan; Bai, Yubai; Li, Tiejin

    2004-02-01

    Highly hydrophilic, uniform and nontoxic magnetic fluids consisting of magnetite (Fe 3O 4) and dextran were prepared. A periodate oxidation method was used to further activate the magnetic dextran, forming magnetic polyaldehyde-dextran, which could be conjugated to biomolecules such as proteins or antibodies. Oxidated Magnetic dextran composites were characterized by TEM, XRD and SQUID magnetometry. Moreover, a flexible, rapid and simple method to detect aldehydes was introduced to the magnetic composite system by utilizing 2,4-dinitrophenylhydrazine reagent. The result of the quantitative analysis of aldehyde was given by thermogravimetric analysis and elemental analysis.

  2. Sodium Nitrite and Sodium Thiosulfate Are Effective Against Acute Cyanide Poisoning When Administered by Intramuscular Injection.

    PubMed

    Bebarta, Vikhyat S; Brittain, Matthew; Chan, Adriano; Garrett, Norma; Yoon, David; Burney, Tanya; Mukai, David; Babin, Michael; Pilz, Renate B; Mahon, Sari B; Brenner, Matthew; Boss, Gerry R

    2017-06-01

    The 2 antidotes for acute cyanide poisoning in the United States must be administered by intravenous injection. In the out-of-hospital setting, intravenous injection is not practical, particularly for mass casualties, and intramuscular injection would be preferred. The purpose of this study is to determine whether sodium nitrite and sodium thiosulfate are effective cyanide antidotes when administered by intramuscular injection. We used a randomized, nonblinded, parallel-group study design in 3 mammalian models: cyanide gas inhalation in mice, with treatment postexposure; intravenous sodium cyanide infusion in rabbits, with severe hypotension as the trigger for treatment; and intravenous potassium cyanide infusion in pigs, with apnea as the trigger for treatment. The drugs were administered by intramuscular injection, and all 3 models were lethal in the absence of therapy. We found that sodium nitrite and sodium thiosulfate individually rescued 100% of the mice, and that the combination of the 2 drugs rescued 73% of the rabbits and 80% of the pigs. In all 3 species, survival in treated animals was significantly better than in control animals (log rank test, P<.05). In the pigs, the drugs attenuated an increase in the plasma lactate concentration within 5 minutes postantidote injection (difference: plasma lactate, saline solution-treated versus nitrite- or thiosulfate-treated 1.76 [95% confidence interval 1.25 to 2.27]). We conclude that sodium nitrite and sodium thiosulfate administered by intramuscular injection are effective against severe cyanide poisoning in 3 clinically relevant animal models of out-of-hospital emergency care. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. Effects of indigo naturalis on colonic mucosal injuries and inflammation in rats with dextran sodium sulphate-induced ulcerative colitis.

    PubMed

    Wang, Yunliang; Liu, Lijuan; Guo, Yi; Mao, Tangyou; Shi, Rui; Li, Junxiang

    2017-08-01

    The effects of indigo naturalis (IN), which is a traditional Chinese herbal formulation, have been clinically demonstrated in treating refractory ulcerative colitis (UC). The present study aimed to verify the effects and mechanisms of IN in experimental UC rats. A total of 48 male Sprague-Dawley rats were randomly divided into six groups: Chow, model, high-dose IN, medium-dose IN, low-dose IN and mesalazine (a bowel-specific aminosalicylate drug) groups. The models were administered 3.5% dextran sodium sulphate solution for 7 days. The treatment groups were administered IN or mesalazine and then sacrificed and sampled on day 8. Disease activity index (DAI), histological damage score (HDS) and myeloperoxidase (MPO) activity were used to evaluate the severity of UC. Colon and serum cytokines were detected using liquid-phase chip technology and the expression of occludin protein in colonic mucosa was assessed by immunohistochemistry and western blot analysis. The results indicated that the oral administration of IN may reduce DAI, HDS and MPO activity. IN also reduced the expression of inflammatory cytokines and increased the expression of colonic mucosal repair-related cytokines and occludin protein. These results highlight the potential of IN as a therapeutic agent for treating UC through its action of inflammation control and colonic mucosal damage repair.

  8. Effects of indigo naturalis on colonic mucosal injuries and inflammation in rats with dextran sodium sulphate-induced ulcerative colitis

    PubMed Central

    Wang, Yunliang; Liu, Lijuan; Guo, Yi; Mao, Tangyou; Shi, Rui; Li, Junxiang

    2017-01-01

    The effects of indigo naturalis (IN), which is a traditional Chinese herbal formulation, have been clinically demonstrated in treating refractory ulcerative colitis (UC). The present study aimed to verify the effects and mechanisms of IN in experimental UC rats. A total of 48 male Sprague-Dawley rats were randomly divided into six groups: Chow, model, high-dose IN, medium-dose IN, low-dose IN and mesalazine (a bowel-specific aminosalicylate drug) groups. The models were administered 3.5% dextran sodium sulphate solution for 7 days. The treatment groups were administered IN or mesalazine and then sacrificed and sampled on day 8. Disease activity index (DAI), histological damage score (HDS) and myeloperoxidase (MPO) activity were used to evaluate the severity of UC. Colon and serum cytokines were detected using liquid-phase chip technology and the expression of occludin protein in colonic mucosa was assessed by immunohistochemistry and western blot analysis. The results indicated that the oral administration of IN may reduce DAI, HDS and MPO activity. IN also reduced the expression of inflammatory cytokines and increased the expression of colonic mucosal repair-related cytokines and occludin protein. These results highlight the potential of IN as a therapeutic agent for treating UC through its action of inflammation control and colonic mucosal damage repair. PMID:28781623

  9. 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.

  10. Pretreatment and Treatment With L-Arginine Attenuate Weight Loss and Bacterial Translocation in Dextran Sulfate Sodium Colitis.

    PubMed

    Andrade, Maria Emília Rabelo; Santos, Rosana das Graças Carvalho Dos; Soares, Anne Danieli Nascimento; Costa, Kátia Anunciação; Fernandes, Simone Odília Antunes; de Souza, Cristina Maria; Cassali, Geovanni Dantas; de Souza, Adna Luciana; Faria, Ana Maria Caetano; Cardoso, Valbert Nascimento

    2016-11-01

    Imbalances in a variety of factors, including genetics, intestinal flora, and mucosal immunity, can contribute to the development of ulcerative colitis and its side effects. This study evaluated the effects of pretreatment or treatment with arginine by oral administration on intestinal permeability, bacterial translocation (BT), and mucosal intestinal damage due to colitis. C57BL/6 mice were distributed into 4 groups: standard diet and water (C: control group), standard diet and dextran sodium sulfate (DSS) solution (Col: colitis group), 2% L-arginine supplementation for 7 days prior to DSS administration and during disease induction (PT: pretreated group), and 2% L-arginine supplementation during disease induction (T: treated group). Colitis was induced by administration of 1.5% DSS for 7 days. After 14 days, intestinal permeability and BT were evaluated; colons were collected for histologic analysis and determination of cytokines; feces were collected for measurement of immunoglobulin A (IgA). The Col group showed increased intestinal permeability (C vs Col: P < .05) and BT (C vs Col: P < .05). In the arginine-supplemented groups (PT and T), this amino acid tended to decrease intestinal permeability. Arginine decreased BT to liver during PT (P < .05) and to blood, liver, spleen, and lung during T (P < .05). Histologic analysis showed that arginine preserved the intestinal mucosa and tended to decreased inflammation. Arginine attenuates weight loss and BT in mice with colitis. © 2015 American Society for Parenteral and Enteral Nutrition.

  11. 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.

  12. [The influence of sodium bicarbonate combined with ulinastatin on cholinesterase activity for patients with acute phoxim pesticide poisoning].

    PubMed

    Zhao, Bo; Yang, Lanju; Xiao, Lei; Sun, Baoquan; Zou, Xianbao; Gao, Dongmei; Jian, Xiandong

    2016-01-01

    To observe the effect of sodium bicarbonate combined with ulinastatin on cholinesterase activity for patients with acute phoxim pesticide poisoning. A total of 67 eligible patients with acute phoxim pesticide poisoning, Who were admitted to the emeryency department of hospital from March 2011 to February 2014, Acording to different treatments au patients were randomly divided into the conventional treatment group (n=34) and the sodium bicarbonate+ulinastatin group (n=35) . The conventional treatment group were given thorough gastric lavage with water, the sodium bicarbonate + ulinastatin group were given gastric lavage with 2% sodium bicarbonate solution. Both groups were given such treatments as catharsis, administration of oxygen, fluid infusion, diuresis, and antidotes such as atropine and pralidoxime methylchloride. On the basis of comprehensive treatment, people in the sodium bicarbonate+ulinastatin group were given 5% sodium bicarbonate injection and ulinastatin. The clinical effect of the two groups were compared. The serum cholinesterase activity of the sodium bicarbonate+ulinastatin group was significantly higher than the conventional treatment group from the 5th day, and the difference was statistically significant (P<0.05) . The total atropine dosage, total pralidoxime methylchloride dosage and hospitalization days were better than the conventional treatment group, and the differences were statistically significant (P<0.05) . The difference in the time of atropinization between the two groups was not statistically significant (P>0.05) . The results of arterial blood pH, HCO3- of the sodium bicarbonate + ulinastatin group were higher than the conventional treatment group, and the difference of HCO3- at the 10th day was statistically significant (P<0.05) . Sodium bicarbonate combined with ulinastatin can improve the therapeutic effect and reduce complications in the treatment of acute phoxim pesticide poisoning, and have beneficial effects on the recovery

  13. 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

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

    PubMed Central

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

    2008-01-01

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

  15. Creating biomimetic polymeric surfaces by photochemical attachment and patterning of dextran

    PubMed Central

    Ferrer, M. Carme Coll; Yang, Shu; Eckmann, David M.; Composto, Russell J.

    2010-01-01

    In this work, we report the preparation of photoactive dextran and demonstrate its utility by photochemically attaching it onto various polymeric substrates. The attachment of homogeneous and patterned dextran films was performed on polyurethane and polystyrene, with detailed analysis of surface morphology, swelling behavior, and the protein resistance of these substrates. The described photoactive dextran and attachment procedure is applicable to a wide variety of substrates while accommodating surfaces with complex surface and geometries. Dextran with azide content between 22 to 0.3 wt% was produced by esterification with p-azidobenzoic acid. Dextran (1.2 wt% azide) was photografted onto plasma oxidized polyurethane and polystyrene and displayed thicknesses of 5 ± 3 nm and 7 ± 3 nm, respectively. The patterned dextran on oxidized polyurethane was patchy with a nominal height difference between dextranized and non-dextranized regions. The azidated dextran on oxidized polystyrene exhibited a distinct step in height. In the presence of PBS buffer, the dextranized regions became smoother and more uniform without affecting the height difference at the oxidized polyurethane boundary. However, the dextranized regions on oxidized polyurethane were observed to swell by a factor of 3 relative to the dried thickness. These dissimilarities were attributed to hydrogen bonding between the dextran and oxidized polyurethane and were confirmed by the photoimmobiliization in the presence of LiCl. The resulting surface was the smoothest of all the azidated dextran samples (RRMS = 1 ± 0.3 nm) and swelled up to 2 times its dried thickness in PBS buffer. The antifouling properties of dextran functionalized surfaces were verified by the selective adsorption of FITC-labeled human albumin only on the non-dextranized regions of the patterned polyurethane and polystyrene substrates. PMID:20712352

  16. Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin.

    PubMed

    Hiramoto, Keiichi; Yokoyama, Satoshi; Yamate, Yurika

    2017-03-01

    We previously reported that ultraviolet (UV) A eye irradiation reduces the ulcerative colitis induced by dextran sodium sulfate (DSS). This study examined the effects of UVA on colon carcinoma induced by azoxymethane (AOM) and DSS. We irradiated the eyes of ICR mice with UVA at a dose of 110 kJ/m 2 using an FL20SBLB-A lamp for the experimental period. In mice treated with these drugs, the symptom of colon carcinoma was reduced by UVA eye irradiation. The levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the blood were increased in AOM + DSS-treated mice; however, those levels were reduced by UVA eye irradiation. The expression of β-endorphin, methionine-enkephalin (OGF), μ-opioid receptor, and opioid growth factor receptor (OGFR) of the colon was increased in the AOM + DSS-treated mice, and these levels were increased further following UVA eye irradiation. When β-endorphin inhibitor was administered, the ameliorative effect of UVA eye irradiation was reduced, and the effect of eye irradiation disappeared entirely following the administration of naltrexone (inhibitor of both opioid receptor and OGFR). These results suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. High-fat diets rich in saturated fat protect against azoxymethane/dextran sulfate sodium-induced colon cancer.

    PubMed

    Enos, Reilly T; Velázquez, Kandy T; McClellan, Jamie L; Cranford, Taryn L; Nagarkatti, Mitzi; Nagarkatti, Prakash S; Davis, J Mark; Murphy, E Angela

    2016-06-01

    High-fat-diet (HFD) consumption is associated with colon cancer risk. However, little is known about how the lipid composition of a HFD can influence prooncogenic processes. We examined the effects of three HFDs differing in the percentage of total calories from saturated fat (SF) (6, 12, and 24% of total caloric intake), but identical in total fat (40%), and a commercially available Western diet (26 and 41% saturated and total fat, respectively) on colon cancer development using the azoxymethane (AOM)/dextran sulfate sodium (DSS) murine model. A second dose-response experiment was performed using diets supplemented with the saturated-fatty-acid (SFA)-rich coconut oil. In experiment 1, we found an inverse association between SF content and tumor burden. Furthermore, increased SF content was associated with reduced inflammation, increased apoptosis, and decreased proliferation. The second dose-response experiment was performed to test whether this effect may be attributed to the SF content of the diets. Consistent with the initial experiment, we found that high SF content was protective, at least in male mice; there was a decrease in mortality in mice consuming the highest concentration of SFAs. To explore a potential mechanism for these findings, we examined colonic mucin 2 (Muc2) protein content and found that the HFDs with the highest SF content had the greatest concentration of Muc2. Our data suggest that high dietary SF is protective in the AOM/DSS model of colon cancer, which may be due, at least in part, to the ability of SF to maintain intestinal barrier integrity through increased colonic Muc2. Copyright © 2016 the American Physiological Society.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Tumor targeting of gene expression through metal-coordinated conjugation with dextran.

    PubMed

    Hosseinkhani, Hossein; Aoyama, Teruyoshi; Ogawa, Osamu; Tabata, Yasuhiko

    2003-03-07

    Tumor targeting of plasmid DNA was achieved through the conjugation of dextran derivatives with chelate residues based on metal coordination. Diethylenetriamine pentaacetic acid (DTPA), spermidine (Sd), and spermine (Sm) were chemically introduced to the hydroxyl groups of dextran to obtain dextran-DTPA, dextran-Sd and dextran-Sm derivatives. Conjugation of the dextran derivative by Zn(2+) coordination decreased the apparent size of the plasmid DNA, depending on the derivative type. The negative zeta potential of plasmid DNA became almost 0 mV after Zn(2+)-coordinated conjugation with dextran-Sm. When the dextran derivative-plasmid DNA conjugates with Zn(2+) coordination were intravenously injected subcutaneously into mice bearing Meth-AR-1 fibrosarcoma, the dextran-Sm-plasmid DNA conjugate significantly enhanced the level of gene expression in the tumor, in contrast to the conjugate of other dextran derivatives and free plasmid DNA. The enhanced gene expression produced by the Zn(2+)-coordinated dextran-Sm-plasmid DNA conjugate was specific to the tumor, whereas a simple mixture of dextran-Sm and plasmid DNA was not effective. The level of gene expression depended on the percentage of chelate residues introduced, the mixing weight ratio of the plasmid DNA/Sm residue used for conjugate preparation, and the plasmid DNA dose. A fluorescent microscopic study revealed that localization of plasmid DNA in the tumor tissue was observed only after injection of the dextran-Sm-plasmid DNA conjugate with Zn(2+) coordination. In addition, the gene expression induced by the conjugate lasted for more than 10 days after the injection. We conclude that Zn(2+)-coordinated dextran-Sm conjugation is a promising way to enable plasmid DNA to target the tumor in gene expression as well as to prolong the duration of gene expression.

  4. The use of dextran post free tissue transfer.

    PubMed

    Ridha, H; Jallali, N; Butler, P E

    2006-01-01

    Dextran has been used in microsurgery to reduce the risk of free tissue transfer loss. A number of regimens which vary considerably in dosage and timing have been published in the literature. Using a postal questionnaire, a survey was conducted to delineate the current practise of UK plastic surgeons. Data were received from 161 plastic surgeons in 51 units (response rate of 61%). Forty-five percent of microsurgeons routinely use dextran post-operatively whilst 29% use alternative thromboprophylaxis. The indications, post-operative regimes and duration of administration of dextran vary significantly amongst surgeons and units. The reported success rates of free tissue transfer and digital replants were 97 and 85.1%, respectively, and was not significantly affected by the use of dextran. We conclude that there is considerable variation amongst UK plastic surgeons regarding thromboprophylaxis post microsurgery. Our data suggest that the use of dextrans does not affect free tissue transfer success rates.

  5. Selenium-Containing Phycocyanin from Se-Enriched Spirulina platensis Reduces Inflammation in Dextran Sulfate Sodium-Induced Colitis by Inhibiting NF-κB Activation.

    PubMed

    Zhu, Chenghui; Ling, Qinjie; Cai, Zhihui; Wang, Yun; Zhang, Yibo; Hoffmann, Peter R; Zheng, Wenjie; Zhou, Tianhong; Huang, Zhi

    2016-06-22

    Selenium (Se) plays an important role in fine-tuning immune responses. Inflammatory bowel disease (IBD) involves hyperresponsive immunity of the digestive tract, and a low Se level might aggravate IBD progression; however, the beneficial effects of natural Se-enriched diets on IBD remain unknown. Previously, we developed high-yield Se-enriched Spirulina platensis (Se-SP) as an excellent organic nutritional Se source. Here we prepared Se-containing phycocyanin (Se-PC) from Se-SP and observed that Se-PC administration effectively reduced the extent of colitis in mouse induced by dextran sulfate sodium. Supplementation with Se-PC resulted in significant protective effects, including mitigation of body weight loss, bloody diarrhea, and colonic inflammatory damage. The anti-inflammatory effects of Se-PC supplementation were found to involve modulation of cytokines, including IL-6, TNF-α, MCP-1, and IL-10. Mechanistically, Se-PC inhibited the activation of macrophages by suppressing the nuclear translocation of NF-κB, which is involved in the transcription of these pro-inflammatory cytokines. These results together suggest potential benefits of Se-PC as a functional Se supplement to reduce the symptoms of IBD.

  6. Preparation and characterization of a dextran-amylase conjugate.

    PubMed

    Marshall, J J

    1976-07-01

    Bacillus amyloliquefaciens alpha-amylase was attached to dextran after activation of the polysaccharide by using a modification of the cyanogen bromide method. The soluble dextran-amylase conjugate was purified by molecular-sieve chromatography. The conjugated enzyme has greater stability than the unmodified enzyme at low pH values, during heat treatment, and on removal of calcium ions with a chelating agent. Attachment of dextran to alpha-amylase did not alter the Michaelis constant of the enzyme acting on starch. The polysaccharide-enzyme conjugate probably consists of a cross-linked aggregate of many dextran and many enzyme molecules, in which a proportion of the enzyme molecules, although not inactivated, are unable to express their activity, except after dextranase treatment.

  7. Properties of chymotrypsin bound covalently to dextran.

    PubMed

    Zlateva, T P; Krysteva, M; Balajthy, Z; Elödi, P

    1988-01-01

    The kinetic properties dextran-chymotrypsin conjugate were studied by means of low molecular weight substrates. It was found that KM, kcat and kcat/KM of dextran chymotrypsin for the hydrolysis of benzoyl-L-tyrosine-ethyl-ester did not differ substantially from those of the free enzyme. However, the data found for kcat of dextran-chymotrypsin and free chymotrypsin assayed for the hydrolysis of three tripeptidyl-p-nitroanilide D-Arg-Val-Trp-pNA, D-Arg-Val-Tyr-pNA, Z-Phe-Pro-Phe-pNA, were definitely different. The inhibition of the modified chymotrypsin with soybean trypsin inhibitor was found to be less pronounced than that with the free enzyme. The effect of potassium and magnesium salts on the inactivation of both enzymes was also studied. The effect of dextran matrix on the catalytic properties and the conformational stability of modified chymotrypsin is discussed.

  8. Acute and chronic respiratory effects of sodium borate particulate exposures.

    PubMed Central

    Wegman, D H; Eisen, E A; Hu, X; Woskie, S R; Smith, R G; Garabrant, D H

    1994-01-01

    This study examined work-related chronic abnormality in pulmonary function and work-related acute irritant symptoms associated with exposure to borate dust in mining and processing operations. Chronic effects were examined by pulmonary function at the beginning and end of a 7-year interval. Time-specific estimates of sodium borate particulate exposures were used to estimate cumulative exposure during the study interval. Change in pulmonary function over the 7 years was found unrelated to the estimate of cumulative exposure during that interval. Exposure-response associations also were examined with respect to short-term peak exposures and incidence of five symptoms of acute respiratory irritation. Hourly measures of health outcome and continuous measures of particulate exposure were made on each subject throughout the day. Whenever a subject reported one of the irritant symptoms, a symptom intensity score was also recorded along with the approximate time of onset. The findings indicated that exposure-response relationships were present for each of the specific symptoms at several symptom intensity levels. The associations were present when exposure was estimated by both day-long and short-term (15-min) time-weighted average exposures. Associations persisted after taking account of smoking, age, and the presence of a common cold. No significant difference in response rate was found between workers exposed to different types of sodium borate dusts. PMID:7889871

  9. Synthesis, characterization and antimicrobial activity of dextran sulphate stabilized silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Cakić, Milorad; Glišić, Slobodan; Nikolić, Goran; Nikolić, Goran M.; Cakić, Katarina; Cvetinov, Miroslav

    2016-04-01

    Dextran sulphate stabilized silver nanoparticles (AgNPs - DS) were synthesized from aqueous solution of silver nitrate (AgNO3) and dextran sulphate sodium salt (DS). The characterization of AgNPs - DS was performed by ultraviolet-visible spectroscopy (UV-VIS), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and antimicrobial activity. The formation of AgNPs - DS was monitored by colour changes of the reaction mixture from yellowish to brown and by measuring the surface plasmon resonance absorption peak in UV-VIS spectra at 420 nm. The SEM analysis was used for size and shape determination of AgNPs - DS. The presence of elemental silver and its crystalline structure in AgNPs - DS were confirmed by EDX and XRD analyses. The possible functional groups of DS responsible for the reduction and stabilization of AgNPs were determinated by FTIR spectroscopy. The AgNPs - DS showed strong antibacterial activity against Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 11778, Bacillus luteus in haus strain, Bacillus subtilis ATTC 6633, Listeria monocytogenes ATCC 15313, Escherichia coli ATTC 25922, Pseudomonas aeruginosa ATTC 27853, Klebsiella pneumoniae ATTC 700603, Proteus vulgaris ATTC 8427, and antifungal activity against Candida albicans ATTC 2091.

  10. Protective effect of dextrans on glucose oxidase denaturation and inactivation.

    PubMed

    Altikatoglu, Melda; Basaran-Elalmis, Yeliz

    2012-08-01

    In the present study, the stabilizing effect of dextrans as additives on the denaturation and inactivation of glucose oxidase (GOD) was investigated. Three different molecular weighted dextrans (M(w) 17.5, 75, 188 kD) were used with different concentrations. Dramatically increased enzyme activities were measured after one hour of incubation of enzyme with additives between 25-40°C in water bath. Highest activity value was measured with 75 kDa molecular weighted dextran (in concentration 30% w/v) at pH 5. Dextran as an additive supplied a long shelf-life to the enzyme at 4°C. In the presence of the 75 kDa dextran, the enzyme was more stable and its activity was increased 2.7-fold at 30°C. In addition, dextran protected GOD against inactivation by a n-heptane/aqueous buffer-stirred system.

  11. Pharmacokinetic alterations of rhubarb anthraquinones in experimental colitis induced by dextran sulfate sodium in the rat.

    PubMed

    Wu, Wen-Jin; Yan, Ru; Li, Ting; Li, Ya-Ping; Zhou, Rui-Na; Wang, Yi-Tao

    2017-02-23

    Rhubarb (Rhei Rhizoma et Radix) is used for the treatment of digestive diseases in traditional medicinal practice in China. Recent studies also support its beneficial activities in alleviating ulcerative colitis (UC). This study aimed to characterize the oral pharmacokinetics of rhubarb anthraquinones, the main bioactive components of this herb, in the experimental chronic colitis rat model induced by dextran sulfate sodium (DSS) and to identify the factors causing the pharmacokinetic alterations. Rats received drinking water (normal group) or 5% DSS for the first 7 days and 3% DSS for additional 14 days (UC group). On day 21 both groups received an oral dose of the rhubarb extract (equivalent to 5.0g crude drug/kg body weight). Plasma anthraquinone aglycones levels were determined directly by an LC-MS/MS method and the total of each anthraquinone (aglycone+conjugates) was quantified after β-glucuronidases hydrolysis. Rhubarb anthraquinones predominantly existed as conjugates in plasma samples from both groups and only free aloe-emodin, rhein and emodin were detected. Compared to the normal rats, both C max and AUC of the three free anthraquinones were increased, while the systemic exposure (AUC) of the total (aglycone+conjugates) of most anthraquinones decreased by UC accompanied by the disappearance of multiple-peak phenomenon in the plasma concentration-time profiles. Gut bacteria from UC rats exhibited a decreased activity in hydrolyzing anthraquinone glycosides to form respective aglycone and there were significant decreases in microbial β-glucosidases and β-glucuronidases activities. Moreover, the intestinal microsomes from UC rats catalyzed glucuronidation of free anthraquinones with higher activities, while the activities of hepatic microsomes were comparable to normal rats. The decreases of β-glucuronidases activity in DSS-induced chronic rat colitis should mainly account for the decreases in systemic exposure and abrogation of enterohepatic

  12. Vincristine sulfate loaded dextran microspheres amalgamated with thermosensitive gel offered sustained release and enhanced cytotoxicity in THP-1, human leukemia cells: In vitro and in vivo study.

    PubMed

    Thakur, Vivek; Kush, Preeti; Pandey, Ravi Shankar; Jain, Upendra Kumar; Chandra, Ramesh; Madan, Jitender

    2016-04-01

    Vincristine sulfate (VCS) is a drug of choice for the treatment of childhood and adult acute lymphocytic leukemia, Hodgkin's, non-Hodgkin's lymphoma as well as solid tumors including sarcomas. However, poor biopharmaceutical and pharmacokinetic traits of VCS like short serum half-life (12 min), high dosing frequency (1.4 mg/m(2) per week for 4 weeks) and extensive protein binding (75%) limit the clinical potential of VCS in cancer therapy. In present investigation, injectable vincristine sulfate loaded dextran microspheres (VCS-Dextran-MSs) were prepared and amalgamated with chitosan-β-glycerophosphate gel (VCS-Dextran-MSs-Gel) to surmount the biopharmaceutical and pharmacokinetic limitations of VCS that consequently induced synergistic sustained release pattern of the drug. Particle size and zeta-potential of VCS-Dextran-MSs were measured to be 6.8 ± 2.4 μm and -18.3 ± 0.11 mV along with the encapsulation efficiency of about 60.4 ± 4.5%. Furthermore, VCS-Dextran-MSs and VCS-Dextran-MSs-Gel exhibited slow release pattern and 94.7% and 95.8% of the drug was released in 72 h and 720 h, respectively. Results from cell viability assay and pharmacokinetic as well as histopathological analysis in mice indicated that VCS-Dextran-MSs-Gel offers superior therapeutic potential and higher AUClast than VCS-Dextran-MSs and drug solution. In conclusion, VCS-Dextran-MSs-Gel warrants further preclinical tumor growth study to scale up the technology. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Antimicrobial activity of chemically modified dextran derivatives.

    PubMed

    Tuchilus, Cristina G; Nichifor, Marieta; Mocanu, Georgeta; Stanciu, Magdalena C

    2017-04-01

    Cationic amphiphilic dextran derivatives with a long alkyl group attached to the reductive end of the polysaccharide chain and quaternary ammonium groups attached as pendent groups to the main dextran backbone were synthesized and tested for their antimicrobial properties against several bacteria and fungi strains. Dependence of antimicrobial activity on both polymer chemical composition (dextran molar mass, length of end alkyl group and chemical structure of ammonium groups) and type of microbes was highlighted by disc-diffusion method (diameter of inhibition zone) and broth microdilution method (minimum inhibitory concentrations). Polymers had antimicrobial activity for all strains studied, except for Pseudomonas aeruginosa ATCC 27853. The best activity against Staphylococcus aureus (Minimun Inhibitory Concentration 60μg/mL) was provided by polymers obtained from dextran with lower molecular mass (Mn=4500), C 12 H 25 or C 18 H 37 end groups, and N,N-dimethyl-N-benzylammonium pendent groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Ultraviolet A: Visible spectral absorbance of the human cornea after transepithelial soaking with dextran-enriched and dextran-free riboflavin 0.1% ophthalmic solutions.

    PubMed

    Lombardo, Marco; Micali, Norberto; Villari, Valentina; Serrao, Sebastiano; Pucci, Giuseppe; Barberi, Riccardo; Lombardo, Giuseppe

    2015-10-01

    To evaluate the stromal concentration of 2 commercially available transepithelial riboflavin 0.1% solutions in human donor corneas with the use of spectrophotometry. University of Calabria, Rende, Italy. Experimental study. The absorbance spectra of 12 corneal tissues were measured in the 330 to 700 nm wavelength range using a purpose-designed spectrophotometry setup before and after transepithelial corneal soaking with a 15% dextran-enriched riboflavin 0.1% solution (n = 6) or a hypotonic dextran-free riboflavin 0.1% solution (n = 6). Both ophthalmic solutions contained ethylenediaminetetraacetic acid and trometamol as enhancers. In addition, 4 deepithelialized corneal tissues underwent stromal soaking with a 20% dextran-enriched riboflavin 0.1% solution and were used as controls. All the riboflavin solutions were applied topically for 30 minutes. The stromal concentration of riboflavin was quantified by analysis of absorbance spectra of the cornea collected before and after application of each solution. The mean stromal riboflavin concentration was 0.012% ± 0.003% (SD), 0.0005% ± 0.0003% (P < .001), and 0.004% ± 0.001% (P < .01) in tissues soaked with 20% dextran-enriched, 15% dextran-enriched, and hypotonic dextran-free solutions, respectively. The difference of stromal riboflavin concentration between the 2 transepithelial solutions was statistically significant (P < .01). Dextran-enriched solutions required complete corneal deepithelialization to permit effective stromal soaking with riboflavin. Nevertheless, riboflavin in hypotonic dextran-free solution with enhancers permeates across stroma through an intact epithelium. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  15. Artemisinin protects against dextran sulfate-sodium-induced inflammatory bowel disease, which is associated with activation of the pregnane X receptor.

    PubMed

    Hu, Donghua; Wang, Yuguang; Chen, Zhiwu; Ma, Zengchun; You, Qing; Zhang, Xianxie; Zhou, Tao; Xiao, Yong; Liang, Qiande; Tan, Hongling; Xiao, Chengrong; Tang, Xianglin; Zhang, Boli; Gao, Yue

    2014-09-05

    Artemisinin has been used to treat malaria for centuries in the context of traditional Chinese medicine. In the present study, the effects of artemisinin on pregnane X receptor (PXR)-mediated CYP3A expression and its therapeutic role in inflammatory bowel disease were investigated. LS174T cells exposed to artemisinin at various concentrations and for different periods of time were examined with respect to the specific induction of CYP3A4 and PXR mRNA expression. Transient transfection experiments showed transcriptional activation of the CYP3A4 gene through artemisinin to be PXR-dependent. An electrophoretic-mobility shift assay (EMSA) showed that artemisinin activates the DNA-binding capacity of the PXR for the CYP3A4 element. These results indicate that the induction of CYP3A4 by artemisinin is mediated through the activation of PXR. Using animal models, it was demonstrated that artemisinin abrogates dextran sulfate sodium (DDS)-induced intestinal inflammation. Preadministration of artemisinin ameliorated the clinical hallmarks of colitis in DSS-treated mice as determined by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. Artemisinin was found to prevent or reduce the severity of colonic inflammation by inducing CYP3A expression by activation of PXR. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. More Efficient Sodium Removal by Ultrafiltration Compared to Diuretics in Acute Heart Failure; Underexplored and Overstated.

    PubMed

    Kazory, Amir

    2016-01-01

    Enhanced removal of sodium has often been cited as an advantage of ultrafiltration (UF) therapy over diuretic-based medical treatment in the management of acute decompensated heart failure. However, so far clinical studies have rarely evaluated the precise magnitude of sodium removal, and this assumption is largely based on the physiologic mechanisms and anecdotal observations that predate the contemporary management of heart failure. Recent data suggest that patients treated with UF experience substantial reduction in urinary sodium excretion possibly due to prolonged intravascular volume contraction. Consequently, the efficient sodium extraction through production of isotonic ultrafiltrate can be offset by urine hypotonicity. Based on the limited currently available data, it seems unlikely that the persistent benefits of UF could be solely explained by its greater efficiency in sodium removal. The design of the future studies should include frequent measurements of urine sodium to precisely compare the impact of UF and diuretics on sodium balance. © 2016 S. Karger AG, Basel.

  17. Anti-Colitic Effects of Kanjangs (Fermented Soy Sauce and Sesame Sauce) in Dextran Sulfate Sodium-Induced Colitis in Mice

    PubMed Central

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

    2014-01-01

    Abstract This study was conducted to investigate the preventive effects of different kanjangs (Korean soy sauces), including acid-hydrolyzed soy sauce (AHSS), fermented soy sauce (FSS), and fermented sesame sauce (FSeS), on 2% dextran sulfate sodium (DSS)-induced ulcerative colitis in C57BL/6J mice. The fermented sauces, particularly FSeS, significantly suppressed DSS-induced body weight loss, increased colon length, and decreased colon weight/length ratios. Histological observations suggested that the fermented sauces prevented edema, mucosal damage, and the loss of crypts induced by DSS compared to the control mice and animals fed AHSS. FSeS and FSS decreased the serum levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6, and IL-17α. mRNA expression of these cytokines as well as that of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in colon mucosa was also inhibited by the two sauces. Our results suggest that fermented sauces, especially FSeS, exert an anticolitic effect partially by reducing the serum levels of proinflammatory cytokines and inhibiting the mRNA expression of these factors in the colon tissue of mice treated with DSS. However, AHSS did not protect against DSS-induced colitis. In addition, low-dose treatment (4 mL/kg) with the fermented sauces resulted in greater anticolitic effects than consumption of a high quantity (8 mL/kg) of the sauces. PMID:25188463

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

    PubMed

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

    2014-09-01

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

  19. Blueberry husks, rye bran and multi-strain probiotics affect the severity of colitis induced by dextran sulphate sodium.

    PubMed

    Håkansson, Asa; Bränning, Camilla; Adawi, Diya; Molin, Göran; Nyman, Margareta; Jeppsson, Bengt; Ahrné, Siv

    2009-01-01

    The enteric microbiota is a pivotal factor in the development of intestinal inflammation in humans but probiotics, dietary fibres and phytochemicals can have anti-inflammatory effects. The aim of this study was to evaluate the therapeutic effect of multi-strain probiotics and two conceivable prebiotics in an experimental colitis model. Sprague-Dawley rats were fed a fibre-free diet alone or in combination with Lactobacillus crispatus DSM 16743, L. gasseri DSM 16737 and Bifidobacterium infantis DSM 15158 and/or rye bran and blueberry husks. Colitis was induced by 5% dextran sulphate sodium (DSS) given by oro-gastric tube. Colitis severity, inflammatory markers, gut-load of lactobacilli and Enterobacteriaceae, bacterial translocation and formation of carboxylic acids (CAs) were analysed. The disease activity index (DAI) was lower in all treatment groups. Viable counts of Enterobacteriaceae were reduced and correlated positively with colitis severity, while DAI was negatively correlated with several CAs, e.g. butyric acid. The addition of probiotics to blueberry husks lowered the level of caecal acetic acid and increased that of propionic acid, while rye bran in combination with probiotics increased caecal CA levels and decreased distal colonic levels. Blueberry husks with probiotics reduced the incidence of bacterial translocation to the liver, colonic levels of myeloperoxidase, malondialdehyde and serum interleukin-12. Acetic and butyric acids in colonic content correlated negatively to malondialdehyde. A combination of probiotics and blueberry husks or rye bran enhanced the anti-inflammatory effects compared with probiotics or dietary fibres alone. These combinations can be used as a preventive or therapeutic approach to dietary amelioration of intestinal inflammation.

  20. Fabrication and characterization of iron oxide dextran composite layers

    NASA Astrophysics Data System (ADS)

    Iconaru, S. L.; Predoi, S. A.; Beuran, M.; Ciobanu, C. S.; Trusca, R.; Ghita, R.; Negoi, I.; Teleanu, G.; Turculet, S. C.; Matei, M.; Badea, Monica; Prodan, A. M.

    2018-02-01

    Super paramagnetic iron oxide nanoparticles such as maghemite have been shown to exhibit antimicrobial properties [1-5]. Moreover, the iron oxide nanoparticles have been proposed as a potential magnetically controllable antimicrobial agent which could be directed to a specific infection [3-5]. The present research has focused on studies of the surface and structure of iron oxide dextran (D-IO) composite layers surface and structure. These composite layers were deposited on Si substrates. The structure of iron oxide dextran composite layers was investigated by X-Ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) while the surface morphology was evaluated by Scanning Electron Microscopy (SEM). The structural characterizations of the iron oxide dextran composite layers revealed the basic constituents of both iron and dextran structure. Furthermore, the in vitro evaluation of the antifungal effect of the complex layers, which have been shown revealed to be active against C. albicans cells at distinct intervals of time, is exhibited. Our research came to confirm the fungicidal effect of iron oxide dextran composite layers. Also, our results suggest that iron oxide dextran surface may be used for medical treatment of biofilm associated Candida infections.

  1. Colonic and Hepatic Modulation by Lipoic Acid and/or N-Acetylcysteine Supplementation in Mild Ulcerative Colitis Induced by Dextran Sodium Sulfate in Rats

    PubMed Central

    Moura, Fabiana Andréa; de Andrade, Kívia Queiroz; de Araújo, Orlando Roberto Pimentel; Santos, Juliana Célia de Farias

    2016-01-01

    Lipoic acid (LA) and N-acetylcysteine (NAC) are antioxidant and anti-inflammatory agents that have not yet been tested on mild ulcerative colitis (UC). This study aims to evaluate the action of LA and/or NAC, on oxidative stress and inflammation markers in colonic and hepatic rat tissues with mild UC, induced by dextran sodium sulfate (DSS) (2% w/v). LA and/or NAC (100 mg·kg·day−1, each) were given, once a day, in the diet, in a pretreatment phase (7 days) and during UC induction (5 days). Colitis induction was confirmed by histological and biochemical analyses (high performance liquid chromatography, spectrophotometry, and Multiplex®). A redox imbalance occurred before an immunological disruption in the colon. NAC led to a decrease in hydrogen peroxide (H2O2), malondialdehyde (MDA) levels, and myeloperoxidase activity. In the liver, DSS did not cause damage but treatments with both antioxidants were potentially harmful, with LA increasing MDA and LA + NAC increasing H2O2, tumor necrosis factor alpha, interferon gamma, and transaminases. In summary, NAC exhibited the highest colonic antioxidant and anti-inflammatory activity, while LA + NAC caused hepatic damage. PMID:27957238

  2. 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

  3. Magnetic catechin-dextran conjugate as targeted therapeutic for pancreatic tumour cells.

    PubMed

    Vittorio, Orazio; Voliani, Valerio; Faraci, Paolo; Karmakar, Biswajit; Iemma, Francesca; Hampel, Silke; Kavallaris, Maria; Cirillo, Giuseppe

    2014-06-01

    Catechin-dextran conjugates have recently attracted a lot of attention due to their anticancer activity against a range of cancer cells. Magnetic nanoparticles have the ability to concentrate therapeutically important drugs due to their magnetic-spatial control and provide opportunities for targeted drug delivery. Enhancement of the anticancer efficiency of catechin-dextran conjugate by functionalisation with magnetic iron oxide nanoparticles. Modification of the coating shell of commercial magnetic nanoparticles (Endorem) composed of dextran with the catechin-dextran conjugate. Catechin-dextran conjugated with Endorem (Endo-Cat) increased the intracellular concentration of the drug and it induced apoptosis in 98% of pancreatic tumour cells placed under magnetic field. The conjugation of catechin-dextran with Endorem enhances the anticancer activity of this drug and provides a new strategy for targeted drug delivery on tumour cells driven by magnetic field. The ability to spatially control the delivery of the catechin-dextran by magnetic field makes it a promising agent for further application in cancer therapy.

  4. Mechanisms of the ultrasound-mediated intracellular delivery of liposomes and dextrans.

    PubMed

    Afadzi, Mercy; Strand, Sabina P; Nilssen, Esben A; Måsøy, Svein-Erik; Johansen, Tonni F; Hansen, Rune; Angelsen, Bjørn A; de L Davies, Catharina

    2013-01-01

    The mechanism involved in the ultrasoundenhanced intracellular delivery of fluorescein-isothiocyanate (FITC)-dextran (molecular weight 4 to 2000 kDa) and liposomes containing doxorubicin (Dox) was studied using HeLa cells and an ultrasound transducer at 300 kHz, varying the acoustic power. The cellular uptake and cell viability were measured using flow cytometry and confocal microscopy. The role of endocytosis was investigated by inhibiting clathrin- and caveolae-mediated endocytosis, as well as macropinocytosis. Microbubbles were found to be required during ultrasound treatment to obtain enhanced cellular uptake. The percentage of cells internalizing Dox and dextran increased with increasing mechanical index. Confocal images and flow cytometric analysis indicated that the liposomes were disrupted extracellularly and that released Dox was taken up by the cells. The percentage of cells internalizing dextran was independent of the molecular weight of dextrans, but the amount of the small 4-kDa dextran molecules internalized per cell was higher than for the other dextrans. The inhibition of endocytosis during ultrasound exposure resulted in a significant decrease in cellular uptake of dextrans. Therefore, the improved uptake of Dox and dextrans may be a result of both sonoporation and endocytosis.

  5. 21 CFR 520.1182 - Iron dextran suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... dose dispenser. (2) Indications for use. For the prevention of iron deficiency anemia in baby pigs. (3... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Iron dextran suspension. 520.1182 Section 520.1182... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1182 Iron dextran suspension...

  6. 21 CFR 520.1182 - Iron dextran suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... dose dispenser. (2) Indications for use. For the prevention of iron deficiency anemia in baby pigs. (3... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Iron dextran suspension. 520.1182 Section 520.1182... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1182 Iron dextran suspension...

  7. 21 CFR 520.1182 - Iron dextran suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... dose dispenser. (2) Indications for use. For the prevention of iron deficiency anemia in baby pigs. (3... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Iron dextran suspension. 520.1182 Section 520.1182... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1182 Iron dextran suspension...

  8. 21 CFR 520.1182 - Iron dextran suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... dose dispenser. (2) Indications for use. For the prevention of iron deficiency anemia in baby pigs. (3... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Iron dextran suspension. 520.1182 Section 520.1182... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1182 Iron dextran suspension...

  9. 21 CFR 520.1182 - Iron dextran suspension.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... dose dispenser. (2) Indications for use. For the prevention of iron deficiency anemia in baby pigs. (3... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Iron dextran suspension. 520.1182 Section 520.1182... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1182 Iron dextran suspension...

  10. Microbial dextran-hydrolyzing enzymes: fundamentals and applications.

    PubMed

    Khalikova, Elvira; Susi, Petri; Korpela, Timo

    2005-06-01

    Dextran is a chemically and physically complex polymer, breakdown of which is carried out by a variety of endo- and exodextranases. Enzymes in many groups can be classified as dextranases according to function: such enzymes include dextranhydrolases, glucodextranases, exoisomaltohydrolases, exoisomaltotriohydrases, and branched-dextran exo-1,2-alpha-glucosidases. Cycloisomalto-oligosaccharide glucanotransferase does not formally belong to the dextranases even though its side reaction produces hydrolyzed dextrans. A new classification system for glycosylhydrolases and glycosyltransferases, which is based on amino acid sequence similarities, divides the dextranases into five families. However, this classification is still incomplete since sequence information is missing for many of the enzymes that have been biochemically characterized as dextranases. Dextran-degrading enzymes have been isolated from a wide range of microorganisms. The major characteristics of these enzymes, the methods for analyzing their activities and biological roles, analysis of primary sequence data, and three-dimensional structures of dextranases have been dealt with in this review. Dextranases are promising for future use in various scientific and biotechnological applications.

  11. Blood pressure and endocrine responses of healthy subjects in cold pressor test after acutely increased dietary sodium intake.

    PubMed

    Arjamaa, O; Mäkinen, T; Turunen, L; Huttunen, P; Leppäluoto, J; Vuolteenaho, O; Rintamäki, H

    2001-05-01

    The objective of the study was to compare blood pressure and endocrine responses in a cold pressure test in young healthy subjects who had shown increased blood pressure during an acutely increased sodium intake. Subjects (n = 53) added 121 mmol sodium into their normal diet for one week. If the mean arterial pressure had increased by a minimum of 5 mmHg compared to the control measure, they were selected for the experiments. The selected subjects (n = 8) were given 121 mmol supplemental sodium d-1 for 14 days after which they immersed the right hand into a cold (+10 degrees C) water bath for 5 min. The blood pressure increased (P < 0.05) during the test and was independent of the sodium intake. The plasma noradrenaline increased from 2.41 +/- 0.38 nmol l-1 to 2.82 +/- 0.42 nmol l-1 (P < 0.05) with normal diet and from 1.85 +/- 0.29 nmol l-1 to 2.40 +/- 0.37 nmol l-1 (P < 0.05) with high sodium diet. The starting concentrations and the endpoint concentrations were statistically similar. The plasma levels of natriuretic peptides (NT-proANP, ANP and BNP) did not change during the test, and the concentrations were independent of the sodium diet. To conclude, acutely increased sodium intake does not change blood pressure or hormonal responses in a cold pressor test in young healthy subjects.

  12. The early effect of dextran sodium sulfate administration on carbachol-induced short-circuit current in distal and proximal colon during colitis development.

    PubMed

    Hock, M; Soták, M; Kment, M; Pácha, J

    2011-01-01

    Increased colonic Cl(-) secretion was supposed to be a causative factor of diarrhea in inflammatory bowel diseases. Surprisingly, hyporesponsiveness to Cl(-) secretagogues was later described in inflamed colon. Our aim was to evaluate changes in secretory responses to cholinergic agonist carbachol in distal and proximal colon during colitis development, regarding secretory activity of enteric nervous system (ENS) and prostaglandins. Increased responsiveness to carbachol was observed in both distal and proximal colon after 3 days of 2 % dextran sodium sulfate (DSS) administration. It was measured in the presence of mucosal Ba(2+) to emphasize Cl(-) secretion. The described increase was abolished by combined inhibitory effect of tetrodotoxin (TTX) and indomethacin. Indomethacin also significantly reduced TTX-sensitive current. On the 7th day of colitis development responsiveness to carbachol decreased in distal colon (compared to untreated mice), but did not change in proximal colon. TTX-sensitive current did not change during colitis development, but indomethacin-sensitive current was significantly increased the 7th day. Decreased and deformed current responses to serosal Ba(2+) were observed during colitis induction, but only in proximal colon. We conclude that besides inhibitory effect of DSS on distal colon responsiveness, there is an early stimulatory effect that manifests in both distal and proximal colon.

  13. Efficacy and safety of parecoxib sodium for acute postoperative pain: A meta-analysis.

    PubMed

    Wei, Wei; Zhao, Tianyun; Li, Yuantao

    2013-08-01

    This meta-analysis was performed to evaluate the efficacy and safety of parecoxib sodium for acute postoperative pain. PubMed, Cochrane Central Register of Controlled Trials, EBSCO, Springer, Ovid and Chinese National Knowledge Infrastructure (CNKI) databases were searched from January 1999 to January 2013 to comprehensively collect randomized controlled trials (RCTs) of parecoxib sodium for acute postoperative pain. The methodological quality of the included RCTs were assessed and the data were extracted by two reviewers independently according to the Cochrane Handbook. Efficacies and safety (respiratory depression, pruritus, fever, headache, and nausea and vomiting) were pooled using meta-analysis performed by Review Manager 5.1 software. Relative risk (RR) and 95% confidence interval (CI) were calculated in a fixed-effects model. Seven RCTs involving 1,939 patients met the inclusion criteria. The results of the meta-analysis revealed that the rate of 'effective' treatment as described by the patients' global evaluation of study medication (PGESM) was higher in the patient-controlled analgesia (PCA) combined with parecoxib sodium group 24, 48, and 72 h after the initial intravenous dose of 40 mg parecoxib compared with that in the control group [PCA alone; RR=1.41, 95% CI (1.13-1.75); RR=1.25, 95% CI (1.15-1.35); and RR=1.30, 95% CI (1.21-1.40), respectively]. The rate of 'ineffective' treatment in the PCA combined with parecoxib sodium group was lower compared with that of the control group [RR=0.43, 95% CI (0.26-0.72); RR= 0.44, 95% CI (0.34-0.57); and RR= 0.33, 95% CI (0.23-0.48), respectively]. Combination of PCA with parecoxib sodium reduced the incidence of postoperative fever [RR=0.34, 95% CI (0.22-0.53)], as well as nausea and vomiting [RR=0.69, 95% CI (0.57-0.83)]; however, it did not significantly reduce respiratory depression [RR= 0.84, 95% CI (0.38-1.83)], pruritus [RR= 0.91, 95% CI (0.54-1.52)] or headache [RR=0.77, 95% CI (0.47-1.28)]. The

  14. Targeting the C-type lectins-mediated host-pathogen interactions with dextran.

    PubMed

    Pustylnikov, Sergey; Sagar, Divya; Jain, Pooja; Khan, Zafar K

    2014-01-01

    Dextran, the α-1,6-linked glucose polymer widely used in biology and medicine, promises new applications. Linear dextran applied as a blood plasma substitute demonstrates a high rate of biocompatibility. Dextran is present in foods, drugs, and vaccines and in most cases is applied as a biologically inert substance. In this review we analyze dextran's cellular uptake principles, receptor specificity and, therefore, its ability to interfere with pathogen-lectin interactions: a promising basis for new antimicrobial strategies. Dextran-binding receptors in humans include the DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin) family receptors: DC-SIGN (CD209) and L-SIGN (the liver and lymphatic endothelium homologue of DC-SIGN), the mannose receptor (CD206), and langerin. These receptors take part in the uptake of pathogens by dendritic cells and macrophages and may also participate in the modulation of immune responses, mostly shown to be beneficial for pathogens per se rather than host(s). It is logical to predict that owing to receptor-specific interactions, dextran or its derivatives can interfere with these immune responses and improve infection outcome. Recent data support this hypothesis. We consider dextran a promising molecule for the development of lectin-glycan interaction-blocking molecules (such as DC-SIGN inhibitors) that could be applied in the treatment of diseases including tuberculosis, influenza, hepatitis B and C, human immunodeficiency virus infection and AIDS, etc. Dextran derivatives indeed change the pathology of infections dependent on DC-SIGN and mannose receptors. Complete knowledge of specific dextran-lectin interactions may also be important for development of future dextran applications in biological research and medicine.

  15. Sivelestat sodium hydrate attenuates acute lung injury by decreasing systemic inflammation in a rat model of severe burns.

    PubMed

    Xiao, X-G; Zu, H-G; Li, Q-G; Huang, P

    2016-01-01

    Patients with severe burns often develop acute lung injury (ALI), systemic inflammatory response syndrome (SIRS) often complicates with ALI. Sivelestat sodium hydrate is an effective drug against ALI. However, the mechanisms of this beneficial effect are still poorly understood. In the current study, we evaluate the effects of sivelestat sodium hydrate on systemic and local inflammatory parameters (neutrophil elastase [NE], interleukin [IL]-8, matrix metalloproteinase [MMP] 2 and 9) in a rat model of severe burns and ALI. And to analyze the correlations between expression of NE and IL-8 and acute lung injury. 48 Sprague-Dawley (SD) rats were divided into 3 groups: normal control group, severe burns injury group and severe burns treated with sivelestat sodium hydrate group (SSI). The lung water content and PaO2 were detected in each group. Pathological manifestations in each group were observed for pathology scoring in SD rats with acute lung injury. ELISA was used for detecting expression of NE and IL-8 in serum and BAL specimens of SD rats in each group. RT-PCR was used to detect mRNA expression of NE and IL-8 in lung tissues of each group. Western blotting was used for detecting protein expression of MMP-2 and MMP-9 in lung tissues of each group. SPSS 18.0 was used for statistical analysis. The PaO2 was significantly increased after sivelestat sodium hydrate intravenous injection. Pathological score and water content of lung tissue were significantly decreased in SSI group compared with severe burns injury group, slightly higher than that normal control group. NE and IL-8 levels significantly decreased in serum, BAL and lung tissue specimens after sivelestat sodium hydrate intravenous injection; Expression of MMP-2 and MMP-9 were significantly up-regulated in severe burns group and showed no significantly changed after sivelestat sodium hydrate intravenous injection. In a rat model of severe burns and ALI, administration of sivelestat sodium hydrate improved

  16. Persistent Epithelial Defects and Corneal Opacity After Collagen Cross-Linking With Substitution of Dextran (T-500) With Dextran Sulfate in Compounded Topical Riboflavin.

    PubMed

    Höllhumer, Roland; Watson, Stephanie; Beckingsale, Peter

    2017-03-01

    Collagen cross-linking (CXL) is a commonly performed procedure to prevent the progression of keratoconus. Riboflavin is an essential part of the procedure, which facilitates both the cross-linking process and protection of intraocular structures. Dextran can be added to riboflavin to create an isotonic solution. This case report highlights the importance of compounding riboflavin with the correct dextran solution. A retrospective case series. Six eyes of 4 male patients with keratoconus aged from 20 to 38 years underwent CXL with substitution of 20% dextran (T-500) with 20% dextran sulfate in a compounded riboflavin 0.1% solution. Postoperatively, persistent corneal epithelial defects, stromal haze, and then scarring occurred. Corneal transplantation was performed for visual rehabilitation but was complicated by graft rejection followed by failure (n = 1 eye), dehiscence (n = 4), cataract (n = 2), post-laser ablation haze (n = 1), and steroid-induced glaucoma (n = 2). The visual outcome was <6/18 in all 6 cases because of irregular astigmatism and stromal haze. Thinning, vascularization, and scarring of the residual host tissue were noted. Substitution of dextran (T-500) with dextran sulfate in riboflavin solutions during CXL results in loss of vision from permanent corneal opacity. Residual host changes may compromise the results of corneal transplantation.

  17. Preparation and characterization of magnetic nanoparticles containing Fe(3)O(4)-dextran-anti-β-human chorionic gonadotropin, a new generation choriocarcinoma-specific gene vector.

    PubMed

    Jingting, Cai; Huining, Liu; Yi, Zhang

    2011-01-01

    To evaluate the feasibility of using magnetic iron oxide (Fe(3)O(4))-dextran-anti-β-human chorionic gonadotropin (HCG) nanoparticles as a gene vector for cellular transfections. Fe(3)O(4)-dextran-anti-β-HCG nanoparticles were synthesized by chemical coprecipitation. The configuration, diameter, and iron content of the nanoparticles were detected by transmission electron microscopy (TEM), light scatter, and atomic absorption spectrophotometry. A3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide assay was used to evaluate the cytotoxicity of Fe(3)O(4)-dextran-anti-β-HCG nanoparticles. Enzyme-linked immunosorbent assay and indirect immunofluorescence were used to evaluate immunoreactivity. The efficiency of absorbing DNA and resisting deoxyribonuclease I (DNase I) digestion when bound to Fe(3)O(4)-dextran-anti-β-HCG nanoparticles was examined by agarose gel electrophoresis. The ability of Fe(3)O(4)-dextran-anti-β-HCG nanoparticles to absorb heparanase antisense oligodeoxynucleotides (AS-ODN) nanoparticles in different cell lines was evaluated by flow cytometry. The tissue distribution of heparanase AS-ODN magnetic nanoparticles in choriocarcinoma tumors transplanted in nude mice was detected by atomic absorption spectrophotometry. TEM demonstrated that the shape of nanoparticles is irregular. Light scatter revealed nanoparticles with a mean diameter of 75.5 nm and an iron content of 37.5 μg/mL. No cytotoxicity was observed when the concentration of Fe(3)O(4)-dextran-anti-β-HCG nanoparticles was <37.5 μg/mL. Fe(3)O(4)-dextran nanoparticles have a satisfactory potential to combine with β-HCG antibody. Agarose gel electrophoresis analysis of binding experiments showed that after treatment with sodium periodate, Fe(3)O(4)-dextran-anti-β-HCG nanoparticles have a satisfactory potential to absorb DNA, and the protection experiment showed that nanoparticles can effectively protect DNA from DNase I digestion. Aldehyde Fe(3)O(4)-dextran

  18. Biophysical properties of carboxymethyl derivatives of mannan and dextran.

    PubMed

    Korcová, Jana; Machová, Eva; Filip, Jaroslav; Bystrický, Slavomír

    2015-12-10

    Mannan from Candida albicans, dextran from Leuconostoc spp. and their carboxymethyl (CM)-derivatives were tested on antioxidant and thrombolytic activities. As antioxidant tests, protection of liposomes against OH radicals and reducing power assay were used. Dextran and mannan protected liposomes in dose-dependent manner. Carboxymethylation significantly increased antioxidant properties of both CM-derivatives up to concentration of 10mg/mL, higher concentrations did not change the protection of liposomes. The reducing power of CM-mannan (DS 0.92) was significantly lower (P<0.05) than underivatized mannan. No reductive activity was found for dextran and CM-dextran. All CM-derivatives demonstrated statistically significant increasing activity compared with underivatized polysaccharides. The highest thrombolytic activity was found using CM-mannan (DS 0.92). The clot lysis here amounted to 68.78 ± 6.52% compared with 0.9% NaCl control (18.3 ± 6.3%). Three-dimensional surface profiles of mannan, dextran, and their CM-derivatives were compared by atomic force microscopy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Enhanced binding by dextran-grafting to Protein A affinity chromatographic media.

    PubMed

    Zhao, Lan; Zhu, Kai; Huang, Yongdong; Li, Qiang; Li, Xiunan; Zhang, Rongyue; Su, Zhiguo; Wang, Qibao; Ma, Guanghui

    2017-04-01

    Dextran-grafted Protein A affinity chromatographic medium was prepared by grafting dextran to agarose-based matrix, followed by epoxy-activation and Protein A coupling site-directed to sulfhydryl groups of cysteine molecules. An enhancement of both the binding performance and the stability was achieved for this dextran-grafted Protein A chromatographic medium. Its dynamic binding capacity was 61 mg immunoglobulin G/mL suction-dried gel, increased by 24% compared with that of the non-grafted medium. The binding capacity of dextran-grafted medium decreased about 7% after 40 cleaning-in-place cycles, much lower than that of the non-grafted medium as decreased about 15%. Confocal laser scanning microscopy results showed that immunoglobulin G was bound to both the outside and the inside of dextran-grafted medium faster than that of non-grafted one. Atomic force microscopy showed that this dextran-grafted Protein A medium had much rougher surface with a vertical coordinate range of ±80 nm, while that of non-grafted one was ±10 nm. Grafted dextran provided a more stereo surface morphology and immunoglobulin G molecules were more easily to be bound. This high-performance dextran-grafted Protein A affinity chromatographic medium has promising applications in large-scale antibody purification. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Development of monoclonal antibody-based sandwich ELISA for detection of dextran.

    PubMed

    Wang, Sheng-Yu; Li, Zhe; Wang, Xian-Jiang; Lv, Sha; Yang, Yun; Zeng, Lian-Qiang; Luo, Fang-Hong; Yan, Jiang-Hua; Liang, Da-Feng

    2014-10-01

    Dextran as anti-nutritional factor is usually a result of bacteria activity and has associated serial problems during the process stream in the sugar industry and in medical therapy. A sensitive method is expected to detect dextran quantitatively. Here we generated four monoclonal antibodies (MAbs) against dextran using dextran T40 conjugated with bovine serum albumin (BSA) as immunogen in our lab following hybridoma protocol. Through pairwise, an MAb named D24 was determined to be conjugated with horseradish peroxidase (HRP) and was used in the establishment of a sensitive sandwich enzyme-linked immunosorbent assay (ELISA) method for determination of dextran, in which MAb D9 was chosen as a capture antibody. The detection limit and working scope of the developed sandwich ELISA method were 3.9 ng/mL and 7.8-500 ng/mL with a correlation coefficient of 0.9909. In addition, the cross-reaction assay demonstrated that the method possessed high specificity with no significant cross-reaction with dextran-related substances, and the recovery rate ranged from 96.35 to 102.00%, with coefficient of variation ranging from 1.58 to 6.94%. These results indicated that we developed a detection system of MAb-based sandwich ELISA to measure dextran and this system should be a potential tool to determine dextran levels.

  1. Impairment of skin barrier function via cholinergic signal transduction in a dextran sulphate sodium-induced colitis mouse model.

    PubMed

    Yokoyama, Satoshi; Hiramoto, Keiichi; Koyama, Mayu; Ooi, Kazuya

    2015-10-01

    Dry skin has been clinically associated with visceral diseases, including liver disease, as well as for our previously reported small intestinal injury mouse model, which have abnormalities in skin barrier function. To clarify this disease-induced skin disruption, we used a dextran sulphate sodium (DSS)-induced colitis mouse model. Following treatment with DSS, damage to the colon and skin was monitored using histological and protein analysis methods as well as the detection of inflammatory mediators in the plasma. Notably, transepidermal water loss was higher, and skin hydration was lower in DSS-treated mice compared to controls. Tumor necrosis factor-alpha (TNF-α), interleukin 6 and NO2-/NO3- levels were also upregulated in the plasma, and a decrease in body weight and colon length was observed in DSS-treated mice. However, when administered TNF-α antibody or an iNOS inhibitor, no change in skin condition was observed, indicating that another signalling mechanism is utilized. Interestingly, the number of tryptase-expressing mast cells, known for their role in immune function via cholinergic signal transduction, was elevated. To evaluate the function of cholinergic signalling in this context, atropine (a muscarinic cholinoceptor antagonist) or hexamethonium (a nicotinic cholinergic ganglion-blocking agent) was administered to DSS-treated mice. Our data indicate that muscarinic acetylcholine receptors (mAChRs) are the primary receptors functioning in colon-to-skin signal transduction, as DSS-induced skin disruption was suppressed by atropine. Thus, skin disruption is likely associated with DSS-induced colitis, and the activation of mast cells via mAChRs is critical to this association. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. 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.

  3. Preparation and drug controlled release of porous octyl-dextran microspheres.

    PubMed

    Hou, Xin; Liu, Yanfei

    2015-01-01

    In this work, porous octyl-dextran microspheres with excellent properties were prepared by two steps. Firstly, dextran microspheres were synthesized by reversed-phase suspension polymerization. Secondly, octyl-dextran microspheres were prepared by the reaction between dextran microspheres and ethylhexyl glycidyl ether and freezing-drying method. Porous structure of microspheres was formed through the interaction between octyl groups and organic solvents. The structure, morphology, dry density, porosity and equilibrium water content of porous octyl-dextran microspheres were systematically investigated. The octyl content affected the properties of microspheres. The results showed that the dry density of microspheres decreased from 2.35 to 1.21 g/ml, porosity increased from 80.68 to 95.05% with the octyl content increasing from 0.49 to 2.28 mmol/g. Meanwhile, the equilibrium water content presented a peak value (90.18%) when the octyl content was 2.25 mmol/g. Octyl-dextran microspheres showed high capacity. Naturally drug carriers play an important role in drug-delivery systems for their biodegradability, wide raw materials sources and nontoxicity. Doxorubicin (DOX) was used as a drug model to examine the drug-loading capacity of porous octyl-dextran microspheres. The drug-loading efficiency increased with the increase in microspheres/drug ratio, while the encapsulation efficiency decreased. When microspheres/drug mass ratio was 4/1, the drug-loading efficiency and encapsulation efficiency were 10.20 and 51.00%, respectively. The release rate of DOX increased as drug content and porosity increased. In conclusion, porous octyl-dextran microspheres were synthesized successfully and have the potential to serve as an effective delivery system in drug controlled release.

  4. 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

  5. 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.

  6. 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.

  7. Dextran/Albumin hydrogel sealant for Dacron(R) vascular prosthesis.

    PubMed

    Lisman, Anna; Butruk, Beata; Wasiak, Iga; Ciach, Tomasz

    2014-05-01

    In this paper, the authors describe a novel type of hydrogel coating prepared from the copolymer of human serum albumin and oxidized dextran. The material was designed as a hydrogel sealant for polyester (Dacron®)-based vascular grafts. Dextran was chosen as a coating material due to its anti-thrombogenic properties. Prepared hydrogels were compared with similar, already known biomaterial made from gelatine with the same cross-linking agent. Obtained hydrogels, prepared from various ratios of oxidized dextran/albumin or oxidized dextran/gelatine, showed different cross-linking densities, which caused differences in swelling, degradation rate and mechanical properties. Permeability tests confirmed the complete tightness of the hydrogel-modified prosthesis. Results showed that application of the hydrogel coating provided leakage-free prosthesis and eliminated the need of pre-clotting.

  8. Synthesis and characterization of dextran-coated iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Predescu, Andra Mihaela; Matei, Ecaterina; Berbecaru, Andrei Constantin; Pantilimon, Cristian; Drăgan, Claudia; Vidu, Ruxandra; Predescu, Cristian; Kuncser, Victor

    2018-03-01

    Synthesis and characterization of iron oxide nanoparticles coated with a large molar weight dextran for environmental applications are reported. The first experiments involved the synthesis of iron oxide nanoparticles which were coated with dextran at different concentrations. The synthesis was performed by a co-precipitation technique, while the coating of iron oxide nanoparticles was carried out in solution. The obtained nanoparticles were characterized by using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction spectrometry, Fourier transform infrared spectroscopy and superconducting quantum interference device magnetometry. The results demonstrated a successful coating of iron oxide nanoparticles with large molar weight dextran, of which agglomeration tendency depended on the amount of dextran in the coating solution. SEM and TEM observations have shown that the iron oxide nanoparticles are of about 7 nm in size.

  9. Anti-inflammatory effects of Lactobacillus brevis K65 on RAW 264.7 cells and in mice with dextran sulphate sodium-induced ulcerative colitis.

    PubMed

    Liu, Y-W; Ong, W-K; Su, Y-W; Hsu, C-C; Cheng, T-H; Tsai, Y-C

    2016-06-01

    Lactic acid bacteria (LAB) with anti-inflammatory effects may be beneficial to the prevention or treatment for inflammation-related diseases, such as inflammatory bowel diseases. In an in vitro assay, heat-killed Lactobacillus brevis K65 (K65) reduced lipopolysaccharide-induced production of nitric oxide, tumour necrosis factor (TNF)-α and prostaglandin E2 in RAW 264.7 cells. In RAW 264.7 cells stably expressing an ind=ucible nitric oxide synthase (iNOS) reporter, viable K65 showed greater inhibition of iNOS production than its heat-killed form. In order to further examine the in vivo anti-inflammatory effect of K65, viable K65 was orally administered to BALB/c mice before and during the period of dextran sulphate sodium (DSS)-induced ulcerative colitis (UC). K65 improved UC symptoms, including reduced the levels of the pro-inflammatory cytokines, TNF-α, interleukin (IL)-6 and IL-1β, and lowered the activity of myeloperoxidase. Furthermore, K65 inhibited TNF-α, cyclo-oxygenase 2, forkhead box P3, and Toll-like receptor 4 mRNA expression in the colonic tissue of DSS-induced UC mice. Taken together, K65, a LAB with in vitro anti-inflammatory activity showed preventive effects on mice with DSS-induced UC by lowering the expression of inflammatory molecules.

  10. Comparison of Corneal Riboflavin Gradients Using Dextran and HPMC Solutions.

    PubMed

    Ehmke, Tobias; Seiler, Theo G; Fischinger, Isaak; Ripken, Tammo; Heisterkamp, Alexander; Frueh, Beatrice E

    2016-12-01

    To determine the riboflavin concentration gradient in the anterior corneal stroma when using hydroxypropyl methylcellulose (HPMC) or dextran as the carrier agent. Four different groups of porcine corneas (5 each) were compared regarding the riboflavin concentration in the anterior stroma. Prior to all experiments, stable hydration conditions were established for the corresponding solution. The dextran groups were treated with 0.1% riboflavin in 20% dextran for 10 and 30 minutes and the HPMC groups with 0.1% riboflavin in 1.1% HPMC for 10 and 30 minutes. After imbibition, nonlinear microscopy and consecutive image analysis were used to determine two-photon fluorescence intensities. To determine the riboflavin concentration, corneas were saturated and measured a second time by two-photon microscopy. With this measurement, a proper correction for absorption and scattering could be performed. Ultraviolet-A (UVA) transmission was measured after the application time for each group. Riboflavin concentration decreased with increasing depth and increased with longer application times in all groups. Comparing the dextran for 30 minutes and HPMC for 10 minutes groups, a significantly higher stromal riboflavin concentration was found within the most anterior 70 µm in the dextran group for 30 minutes, whereas deeper than 260 µm HPMC-assisted imbibition for 10 minutes yielded higher concentrations. In dextran-treated corneas, values obtained from pachymetry were substantially reduced, whereas HPMC-assisted imbibition led to a decent swelling. UVA transmission values were higher in dextran-assisted imbibition than in HPMC-assisted imbibition. Stromal riboflavin gradients are similar when applied in dextran for 30 minutes and HPMC for 10 minutes. When using HPMC solutions, a shallower cross-linked volume is expected due to a higher corneal hydration. [J Refract Surg. 2016;32(12):798-802.]. Copyright 2016, SLACK Incorporated.

  11. Molecular self assembly of mixed comb-like dextran surfactant polymers for SPR virus detection.

    PubMed

    Mai-Ngam, Katanchalee; Kiatpathomchai, Wansika; Arunrut, Narong; Sansatsadeekul, Jitlada

    2014-11-04

    The synthesis of two comb-like dextran surfactant polymers, that are different in their dextran molecular weight (MW) distribution and the presence of carboxylic groups, and their characterization are reported. A bimodal carboxylic dextran surfactant polymer consists of poly(vinyl amine) (PVAm) backbone with carboxyl higher MW dextran, non-functionalized lower MW dextran and hydrophobic hexyl branches; while a monomodal dextran surfactant polymer is PVAm grafted with non-functionalized lower MW dextran and hexyl branches. Layer formation of non-covalently attached dextran chains with bimodal MW distributions on a surface plasmon resonance (SPR) chip was investigated from the perspective of mixed physisorption of the bimodal and monomodal surfactant polymers. Separation distances between the carboxylic longer dextran side chains within the bimodal surfactant polymer and between the whole bimodal surfactant molecules on the chip surface could be well-controlled. SPR analysis of shrimp yellow head virus using our mixed surfactant chips showed dependence on synergetic adjustment of these separation distances. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Efficacy and safety of parecoxib sodium for acute postoperative pain: A meta-analysis

    PubMed Central

    WEI, WEI; ZHAO, TIANYUN; LI, YUANTAO

    2013-01-01

    This meta-analysis was performed to evaluate the efficacy and safety of parecoxib sodium for acute postoperative pain. PubMed, Cochrane Central Register of Controlled Trials, EBSCO, Springer, Ovid and Chinese National Knowledge Infrastructure (CNKI) databases were searched from January 1999 to January 2013 to comprehensively collect randomized controlled trials (RCTs) of parecoxib sodium for acute postoperative pain. The methodological quality of the included RCTs were assessed and the data were extracted by two reviewers independently according to the Cochrane Handbook. Efficacies and safety (respiratory depression, pruritus, fever, headache, and nausea and vomiting) were pooled using meta-analysis performed by Review Manager 5.1 software. Relative risk (RR) and 95% confidence interval (CI) were calculated in a fixed-effects model. Seven RCTs involving 1,939 patients met the inclusion criteria. The results of the meta-analysis revealed that the rate of ‘effective’ treatment as described by the patients’ global evaluation of study medication (PGESM) was higher in the patient-controlled analgesia (PCA) combined with parecoxib sodium group 24, 48, and 72 h after the initial intravenous dose of 40 mg parecoxib compared with that in the control group [PCA alone; RR=1.41, 95% CI (1.13–1.75); RR=1.25, 95% CI (1.15–1.35); and RR=1.30, 95% CI (1.21–1.40), respectively]. The rate of ‘ineffective’ treatment in the PCA combined with parecoxib sodium group was lower compared with that of the control group [RR=0.43, 95% CI (0.26–0.72); RR= 0.44, 95% CI (0.34–0.57); and RR= 0.33, 95% CI (0.23–0.48), respectively]. Combination of PCA with parecoxib sodium reduced the incidence of postoperative fever [RR=0.34, 95% CI (0.22–0.53)], as well as nausea and vomiting [RR=0.69, 95% CI (0.57–0.83)]; however, it did not significantly reduce respiratory depression [RR= 0.84, 95% CI (0.38–1.83)], pruritus [RR= 0.91, 95% CI (0.54–1.52)] or headache [RR=0.77, 95

  13. Structural and biocompatibility properties of dextran from Weissella cibaria JAG8 as food additive.

    PubMed

    Tingirikari, Jagan Mohan Rao; Kothari, Damini; Shukla, Rishikesh; Goyal, Arun

    2014-09-01

    Dextran produced from Weissella cibaria JAG8 was purified and characterized. The molecular mass of dextran as determined by the gel filtration and copper bicinchoninate method was approximately, 800 kDa. Monosaccharide analysis revealed that the polysaccharide comprised only glucose units. Dynamic light scattering study confirmed the mono-disperse nature of dextran with hydrodynamic radius of 900 nm. Surface morphology study of dextran by scanning electron microscopy showed the porous web like structure. Cytotoxicity studies on human cervical cancer (HeLa) cell line showed non-toxic and biocompatible nature of dextran. The relative browning for dextran from W. cibaria JAG8 was similar to commercial prebiotic Nutraflora P-95 and 3-fold lower than Raftilose P-95. Synthesis of dextran by dextransucrase treated, sucrose-supplemented skimmed milk revealed the promising potential of dextran as a food additive.

  14. Anti-inflammatory effect of chlorogenic acid on the IL-8 production in Caco-2 cells and the dextran sulphate sodium-induced colitis symptoms in C57BL/6 mice.

    PubMed

    Shin, Hee Soon; Satsu, Hideo; Bae, Min-Jung; Zhao, Zhaohui; Ogiwara, Haru; Totsuka, Mamoru; Shimizu, Makoto

    2015-02-01

    Chlorogenic acid (CHA) is an antioxidant polyphenol prevalent in human diet, with coffee, fruits, and vegetables being its main source. Effects of CHA and CHA metabolites were evaluated on the IL-8 production in human intestinal Caco-2 cells induced by combined stimulation with tumour necrosis factor alpha (TNFα) and H2O2. CHA and caffeic acid (CA) inhibited TNFα- and H2O2-induced IL-8 production. We also examined the in vivo effects of CHA and CA using dextran sulphate sodium (DSS)-induced colitis in mice. CHA attenuated DSS-induced body weight loss, diarrhea, fecal blood, and shortening of colon and dramatically improved colitis histological scores. Furthermore, increases in the mRNA expression of colonic macrophage inflammatory protein 2 and IL-1β, which were induced by DSS, were significantly suppressed by CHA supplementation. These results suggest that dietary CHA use may aid in the prevention of intestinal inflammatory conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. 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.

  16. 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.

  17. 21 CFR 186.1275 - Dextrans.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... by bacterial fermentation of sucrose. Commercially available dextrans are synthesized from sucrose by Leuconostoc mesenteroides strain NRRL B-512(F). Partial depolymerization and purification of the fermented...

  18. Intraoperative use of dextran is associated with cardiac complications after carotid endarterectomy

    PubMed Central

    Farber, Alik; Tan, Tze-Woei; Rybin, Denis; Kalish, Jeffrey A.; Hamburg, Naomi M.; Doros, Gheorghe; Goodney, Philip P.; Cronenwett, Jack L.

    2013-01-01

    Objective Although dextran has been theorized to diminish the risk of stroke associated with carotid endarterectomy (CEA), variation exists in its use. We evaluated outcomes of dextran use in patients undergoing CEA to clarify its utility. Methods We studied all primary CEAs performed by 89 surgeons within the Vascular Study Group of New England database (2003–2010). Patients were stratified by intraoperative dextran use. Outcomes included perioperative death, stroke, myocardial infarction (MI), and congestive heart failure (CHF). Group and propensity score matching was performed for risk-adjusted comparisons, and multivariable logistic and gamma regressions were used to examine associations between dextran use and outcomes. Results There were 6641 CEAs performed, with dextran used in 334 procedures (5%). Dextran-treated and untreated patients were similar in age (70 years) and symptomatic status (25%). Clinical differences between the cohorts were eliminated by statistical adjustment. In crude, group-matched, and propensity-matched analyses, the stroke/death rate was similar for the two cohorts (1.2%). Dextran-treated patients were more likely to suffer postoperative MI (crude: 2.4% vs 1.0%; P = .03; group-matched: 2.4% vs 0.6%; P = .01; propensity-matched: 2.4% vs 0.5%; P = .003) and CHF (2.1% vs 0.6%; P = .01; 2.1% vs 0.5%; P = .01; 2.1% vs 0.2%; P < .001). In multivariable analysis of the crude sample, dextran was associated with a higher risk of postoperative MI (odds ratio, 3.52; 95% confidence interval, 1.62–7.64) and CHF (odds ratio, 5.71; 95% confidence interval, 2.35–13.89). Conclusions Dextran use was not associated with lower perioperative stroke but was associated with higher rates of MI and CHF. Taken together, our findings suggest limited clinical utility for routine use of intraoperative dextran during CEA. PMID:23337295

  19. Oral administration of probiotic bacteria (E. coli Nissle, E. coli O83, Lactobacillus casei) influences the severity of dextran sodium sulfate-induced colitis in BALB/c mice.

    PubMed

    Kokesová, A; Frolová, L; Kverka, M; Sokol, D; Rossmann, P; Bártová, J; Tlaskalová-Hogenová, H

    2006-01-01

    Our study examined whether repeated preventive oral administration of live probiotic bacterial strains Escherichia coli O83:K24:H31 (Ec O83), Escherichia coli Nissle 1917 O6:K5:H1 (Ec Nis) and Lactobacillus casei DN 114001 (Lc) can protect mice against dextran sodium sulfate (DSS)-induced colitis. A significant decrease in average symptom score was observed in Ec O83-, Ec Nis- and Lc-pretreated group (p < 0.05). Significant differences in body mass loss between Lc pretreated mice with DSS-induced colitis were found when compared with nontreated mice (p < 0.05). PBS pretreated mice had a significantly shorter colon than Ec O83-, Ec Nis- and Lc-pretreated mice (p < 0.05). Administration of Lc significantly decreased the severity of DSS induced histological marks of inflammation (p < 0.05). A significant difference (p < 0.05) was also found in specific IgA level against given probiotic in enteral fluid between colitic mice and healthy mice pretreated with Ec 083 and Ec Nis.

  20. Production & Characterization of a Unique Dextran from an Indigenous Leuconostoc mesenteroides CMG713

    PubMed Central

    Sarwat, Farwa; Qader, Shah Ali Ul; Aman, Afsheen; Ahmed, Nuzhat

    2008-01-01

    On the basis of high enzyme activity a newly isolated strain of L. mesenteroides CMG713 was selected for dextran production. For maximum yield of dextran, effects of various parameters such as pH, temperature, sucrose concentration and incubation period were studied. L. mesenteroides CMG713 produced maximum dextran after 20 hours of incubation at 30ºC with 15% sucrose at pH 7.0. The molecular mass distribution of dextran produced by this strain showed that its molecular mass was about 2.0 million Da. Dextran analysis by 13C-NMR spectrometry showed no signals corresponding to any other linkages except α-(1→6) glycosidic linkage in the main chain, which has not been reported before. Physico-chemical properties of this unique dextran were also studied. These optimised conditions could be used for the commercial production of this unique high molecular weight dextran, which have significant industrial perspectives. PMID:18953402

  1. Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon.

    PubMed

    Rai, Gopal; Yadav, Awesh K; Jain, Narendra K; Agrawal, Govind P

    2016-01-01

    Objective of the present investigation was to prepare and evaluate the potential of enteric coated dextran microspheres for colon targeting of 5-fluorouracil (5-FU). Dextran microspheres were prepared by emulsification-crosslinking method and the formulation variables studied included different molecular weights of dextran, drug:polymer ratio, volume of crosslinking agent, stirring speed and time. Enteric coating (Eudragit S-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method using different coat:core ratios (4:1 or 8:1). Uncoated and coated dextran microspheres were characterized by particle size, surface morphology, entrapment efficiency, DSC, in vitro drug release in the presence of dextranase and 2% rat cecal contents. The release study of 5-FU from coated dextran microspheres was pH dependent. No release was observed at acidic pH; however, the drug was released quickly where Eudragit starts solublizing there was continuous release of drug from the microspheres. Organ distribution study was suggested that coated dextran microspheres retard the release of drug in gastric and intestinal pH environment and released of drug from microspheres in colon due to the degradation of dextran by colonic enzymes.

  2. Low cytotoxic tissue adhesive based on oxidized dextran and epsilon-poly-L-lysine.

    PubMed

    Hyon, Suong-Hyu; Nakajima, Naoki; Sugai, Hajime; Matsumura, Kazuaki

    2014-08-01

    A novel adhesive hydrogel consisting of dextran and epsilon-poly(L-lysine) (dextran-PL) with multiple biomedical applications was developed. Periodate oxidation in aqueous media almost stoichiometrically introduces aldehyde groups in dextran molecules, and aldehyde dextran can react with the primary amino groups in epsilon-PL (ɛ-PL) at neutral pH to form a hydrogel. The gelation time of the hydrogel can be easily controlled by the extent of oxidation in dextran and of the acylation in ɛ-PL by anhydrides. The shear adhesion strength of dextran-PL was 10 times higher than that of fibrin glue, when wet collagen sheets were selected as test specimens. The cytotoxicity of aldehyde dextran and ɛ-PL were 1000 times lower than that of glutaraldehyde and poly(allylamine). The considerably low cytotoxicity of aldehyde dextran could be ascribed to its low reactivity with amine species when compared with glutaraldehyde. In contrast, a high reactivity of amino groups in ɛ-PL was observed when compared with glycine, L-lysine, and gelatin, which could be explained by their poor dissociation at neutral pH, thus leading to low cytotoxicity. © 2013 Wiley Periodicals, Inc.

  3. 21 CFR 186.1275 - Dextrans.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... weight polysaccharides produced by bacterial fermentation of sucrose. Commercially available dextrans are... purification of the fermented mixture shall produce a product that is free of viable microorganisms. (b) The...

  4. 21 CFR 186.1275 - Dextrans.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... weight polysaccharides produced by bacterial fermentation of sucrose. Commercially available dextrans are... purification of the fermented mixture shall produce a product that is free of viable microorganisms. (b) The...

  5. 21 CFR 186.1275 - Dextrans.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... weight polysaccharides produced by bacterial fermentation of sucrose. Commercially available dextrans are... purification of the fermented mixture shall produce a product that is free of viable microorganisms. (b) The...

  6. 21 CFR 186.1275 - Dextrans.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... weight polysaccharides produced by bacterial fermentation of sucrose. Commercially available dextrans are... purification of the fermented mixture shall produce a product that is free of viable microorganisms. (b) The...

  7. Targeting the C-type Lectins-Mediated Host-Pathogen Interactions with Dextran

    PubMed Central

    Pustylnikov, Sergey; Sagar, Divya; Jain, Pooja; Khan, Zafar K.

    2017-01-01

    Dextran, the α-1,6-linked glucose polymer widely used in biology and medicine, promises new applications. Linear dextran applied as a blood plasma substitute demonstrates a high rate of biocompatibility. Dextran is present in foods, drugs, and vaccines and in most cases is applied as a biologically inert substance. In this review we analyze dextran’s cellular uptake principles, receptor specificity and, therefore, its ability to interfere with pathogen–lectin interactions: a promising basis for new antimicrobial strategies. Dextran-binding receptors in humans include the DC-SIGN (dendritic cell–specific intercellular adhesion molecule 3-grabbing nonintegrin) family receptors: DC-SIGN (CD209) and L-SIGN (the liver and lymphatic endothelium homologue of DC-SIGN), the mannose receptor (CD206), and langerin. These receptors take part in the uptake of pathogens by dendritic cells and macrophages and may also participate in the modulation of immune responses, mostly shown to be beneficial for pathogens per se rather than host(s). It is logical to predict that owing to receptor-specific interactions, dextran or its derivatives can interfere with these immune responses and improve infection outcome. Recent data support this hypothesis. We consider dextran a promising molecule for the development of lectin–glycan interaction-blocking molecules (such as DC-SIGN inhibitors) that could be applied in the treatment of diseases including tuberculosis, influenza, hepatitis B and C, human immunodeficiency virus infection and AIDS, etc. Dextran derivatives indeed change the pathology of infections dependent on DC-SIGN and mannose receptors. Complete knowledge of specific dextran–lectin interactions may also be important for development of future dextran applications in biological research and medicine. PMID:25224349

  8. Dietary folate does not significantly affect the intestinal microbiome, inflammation or tumorigenesis in azoxymethane-dextran sodium sulphate-treated mice.

    PubMed

    MacFarlane, Amanda J; Behan, Nathalie A; Matias, Fernando M G; Green, Judy; Caldwell, Don; Brooks, Stephen P J

    2013-02-28

    Inflammatory bowel disease (IBD) is a risk factor for the development of colon cancer. Environmental factors including diet and the microflora influence disease outcome. Folate and homocysteine have been associated with IBD-mediated colon cancer but their roles remain unclear. We used a model of chemically induced ulcerative colitis (dextran sodium sulphate (DSS)) with or without the colon carcinogen azoxymethane (AOM) to determine the impact of dietary folic acid (FA) on colonic microflora and the development of colon tumours. Male mice (n 15 per group) were fed a FA-deficient (0 mg/kg), control (2 mg/kg) or FA-supplemented (8 mg/kg) diet for 12 weeks. Folate status was dependent on the diet (P< 0·001) and colitis-induced treatment (P= 0·04) such that mice with colitis had lower circulating folate. FA had a minimal effect on tumour initiation, growth and progression, although FA-containing diets tended to be associated with a higher tumour prevalence in DSS-treated mice (7-20 v. 0%, P= 0·08) and the development of more tumours in the distal colon of AOM-treated mice (13-83% increase, P= 0·09). Folate deficiency was associated with hyperhomocysteinaemia (P< 0·001) but homocysteine negatively correlated with tumour number (r - 0·58, P= 0·02) and load (r - 0·57, P= 0·02). FA had no effect on the intestinal microflora. The present data indicate that FA intake has no or little effect on IBD or IBD-mediated colon cancer in this model and that hyperhomocysteinaemia is a biomarker of dietary status and malabsorption rather than a cause of IBD-mediated colon cancer.

  9. 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.

  10. 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

  11. Sodium Butyrate Protects against Severe Burn-Induced Remote Acute Lung Injury in Rats

    PubMed Central

    Liu, Sheng; Guo, Feng; Sun, Li; Wang, Yong-Jie; Sun, Ye-Xiang; Chen, Xu-Lin

    2013-01-01

    High-mobility group box 1 protein (HMGB1), a ubiquitous nuclear protein, drives proinflammatory responses when released extracellularly. It plays a key role as a distal mediator in the development of acute lung injury (ALI). Sodium butyrate, an inhibitor of histone deacetylase, has been demonstrated to inhibit HMGB1 expression. This study investigates the effect of sodium butyrate on burn-induced lung injury. Sprague–Dawley rats were divided into three groups: 1) sham group, sham burn treatment; 2) burn group, third-degree burns over 30% total body surface area (TBSA) with lactated Ringer’s solution for resuscitation; 3) burn plus sodium butyrate group, third-degree burns over 30% TBSA with lactated Ringer’s solution containing sodium butyrate for resuscitation. The burned animals were sacrificed at 12, 24, and 48 h after burn injury. Lung injury was assessed in terms of histologic changes and wet weight to dry weight (W/D) ratio. Tumor necrosis factor (TNF)-α and interleukin (IL)-8 protein concentrations in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme-linked immunosorbent assay, and HMGB1 expression in the lung was determined by Western blot analysis. Pulmonary myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to reflect neutrophil infiltration and oxidative stress in the lung, respectively. As a result, sodium butyrate significantly inhibited the HMGB1 expressions in the lungs, reduced the lung W/D ratio, and improved the pulmonary histologic changes induced by burn trauma. Furthermore, sodium butyrate administration decreased the TNF-α and IL-8 concentrations in BALF and serum, suppressed MPO activity, and reduced the MDA content in the lungs after severe burn. These results suggest that sodium butyrate attenuates inflammatory responses, neutrophil infiltration, and oxidative stress in the lungs, and protects against remote ALI induced by severe burn, which is associated with inhibiting HMGB1

  12. Spot urine sodium excretion as prognostic marker in acutely decompensated heart failure: the spironolactone effect.

    PubMed

    Ferreira, João Pedro; Girerd, Nicolas; Medeiros, Pedro Bettencourt; Santos, Mário; Carvalho, Henrique Cyrne; Bettencourt, Paulo; Kénizou, David; Butler, Javed; Zannad, Faiez; Rossignol, Patrick

    2016-06-01

    Loop diuretic resistance characterized by inefficient sodium excretion complicates many patients with acutely decompensated heart failure (ADHF). Mineralocorticoid receptor antagonists (MRAs) in natriuretic doses may improve spot urine sodium excretion and outcomes. Our primary aim was to assess the association of high-dose spironolactone with short-term spot urine sodium excretion, and our secondary aim was to determine if this higher short-term spot urine sodium excretion is associated with reduction in the composite clinical outcome (of cardiovascular mortality and/or ADHF hospitalization) event rate at 180 days. Single-centre, non-randomized, open-label study enrolling 100 patients with ADHF. Patients were treated with standard ADHF therapy alone (n = 50) or oral spironolactone 100 mg/day plus standard ADHF therapy (n = 50). Spot urine samples were collected at day 1 and day 3 of hospitalization. Spironolactone group had significantly higher spot urine sodium levels compared to standard care group at day 3 (84.13 ± 28.71 mmol/L vs 70.74 ± 34.43 mmol/L, p = 0.04). The proportion of patients with spot urinary sodium <60 mmol/L was lower in spironolactone group at day 3 (18.8 vs 45.7, p = 0.01). In multivariate analysis, spironolactone was independently associated with increased spot urinary sodium and urinary sodium/potassium ratio of >2 at day 3 (both, p < 0.05). Higher spot urine sodium levels were associated with a lower event rate [HR for urinary sodium >100 mmol/L = 0.16 (0.06-0.42), p < 0.01, compared to <60], and provided a significant prognostic gain measured by net reclassification indexes. Spot urinary sodium levels >60 mmol/L and urinary sodium/potassium ratio >2 measured at day 3 of hospitalization for ADHF are associated with improved mid-term outcomes. Spironolactone is associated with increased spot urinary sodium and sodium/potassium ratio >2.

  13. Intravenous iron-dextran: studies on unsaturated iron-binding capacity

    PubMed Central

    Cox, J. S. G.; Moss, G. F.; Bremner, I.; Reason, Janet

    1968-01-01

    A method is described for measuring the plasma unsaturated iron-binding capacity in the presence of very high concentrations of iron as iron-dextran. The procedure utilizes 59Fe to label the apotransferrin with subsequent separation of ionic iron from transferrin-bound iron on an ion exchange or Sephadex G.25 column. The unsaturated iron-binding capacity has been measured in rabbits and dogs after intravenous injection of iron-dextran and in human subjects after total dose infusion of iron-dextran. No evidence of saturation of the unsaturated iron-binding capacity was found even when the plasma iron values were greater than 40,000 μg Fe/100 ml. PMID:5697365

  14. Enteric-coated epichlorohydrin crosslinked dextran microspheres for site-specific delivery to colon.

    PubMed

    Rai, Gopal; Yadav, Awesh K; Jain, Narendra K; Agrawal, Govind P

    2015-01-01

    Enteric-coated epichlorohydrin crosslinked dextran microspheres containing 5-Fluorouracil (5-FU) for colon drug delivery was prepared by emulsification-crosslinking method. The formulation variables studied includes different molecular weights of dextran, volume of crosslinking agent, stirring speed, time and temperature. Dextran microspheres showed mean entrapment efficiencies ranging between 77 and 87% and mean particle size ranging between 10 and 25 µm. About 90% of drug was released from uncoated dextran microspheres within 8 h, suggesting the fast release and indicated the drug loaded in uncoated microspheres, released before they reached colon. Enteric coating (Eudragit-S-100 and Eudragit-L-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method. The release study of 5-FU from coated dextran microspheres was complete retardation in simulated gastric fluid (pH 1.2) and once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microspheres was observed. Further, the release of drug was found to be higher in the presence of dextranase and rat caecal contents, indicating the susceptibility of dextran microspheres to colonic enzymes. Organ distribution and pharmacokinetic study in albino rats was performed to establish the targeting potential of optimized formulation in the colon.

  15. Preparation, characterization and dynamical mechanical properties of dextran-coated iron oxide nanoparticles (DIONPs).

    PubMed

    Can, Hatice Kaplan; Kavlak, Serap; ParviziKhosroshahi, Shahed; Güner, Ali

    2018-03-01

    Dextran-coated iron oxide nanoparticles (DIONPs) with appropriate surface chemistry exhibit many interesting properties that can be exploited in a variety of biomedical applications such as magnetic resonance imaging (MRI) contrast enhancement, tissue repair, hyperthermia, drug delivery and in cell separation. This paper reports the experimental detail for preparation, characterization and investigation of thermal and dynamical mechanical characteristics of the dextran-coated Fe 3 O 4 magnetic nanoparticles. In our work, DIONPs were prepared in a 1:2 ratio of Fe(II) and Fe(III) salt in the HCl solution with NaOH at given temperature. The obtained dextran-coated iron-oxide nanoparticles structure-property correlation was characterized by spectroscopic methods; attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and XRD. Coating dextran on the iron-oxide proof of important peaks can be seen from the ATR-FTIR. Dramatic crystallinity increment can be observed from the XRD pattern of the iron-oxide dextran nanoparticles. The thermal analysis was examined by differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and differential thermal analysis (DTA). Dynamical mechanical properties of dextran nanoparticles were analysed by dynamic mechanical analysis (DMA). Thermal stability of the iron oxide dextran nanoparticles is higher than that of the dextran.

  16. Antigen size and charge in immune complex glomerulonephritis. II. Passive induction of immune deposits with dextran-anti-dextran immune complexes.

    PubMed Central

    Isaacs, K. L.; Miller, F.

    1983-01-01

    Utilizing dextrans of restricted sizes (10,000, 70,000, 500,000 daltons), modified with regard to charge (neutral, polycationic, polyanionic) and an anti-dextran murine IgA myeloma, W3129, the authors have examined a model that may be used in the study of the combined effect of size and charge on renal deposition of immune complexes. Polycationic DEAE dextran complexes, using the 10,000 dalton antigen, showed a mesangiocapillary pattern of deposition. The other antigens showed focal to diffuse mesangial localization of varying degree. This indicates the potential usefulness of this system in examining the factors important in glomerular immune injury. The relevance to other observations, importance of polysaccharide antigens, and role in circulating versus in situ or "planted" immune complex models are considered. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:6190406

  17. Ultrasound enhances in vivo tumor expression of plasmid DNA by PEG-introduced cationized dextran.

    PubMed

    Hosseinkhani, Hossein; Tabata, Yasuhiko

    2005-11-28

    This study is an investigation to experimentally confirm whether or not ultrasound (US) irradiation is effective in enhancing the in vivo gene expression of plasmid DNA in tumor. Dextran was cationized by introducing spermine to the hydroxyl groups to allow to polyionically complex with a plasmid DNA. The cationized dextran prepared was additionally modified with poly(ethylene glycol) (PEG) molecules which have an active ester and methoxy groups at each terminal, to obtain cationized dextran with different percentages of PEG introduced. Various cationized dextrans with or without PEG introduction were mixed with a plasmid DNA of LacZ to form cationized dextran-plasmid DNA complexes. Electrophoretical examination revealed that the plasmid DNA was complexed both with the cationized dextran and PEG-introduced cationized dextran, irrespective of the PEG introduction percentage, although the higher N/P ratio was needed for plasmid DNA complexation with the latter. By complexation with the cationized dextran, the zeta potential of plasmid DNA was changed to be positive. The charge of PEG-introduced cationized dextran-plasmid DNA complexes became close to 0 mV as their percentage of PEG introduced increased, although the molecular size was about 250 nm, irrespective of the PEG introduction. When cationized dextran-plasmid DNA complexes with or without PEG introduction were intravenously injected to mice carrying a subcutaneous Meth-AR-1 fibrosarcoma mass and the subsequent US irradiation to the tumor mass percutaneously, the PEG-introduced cationized dextran-plasmid DNA complex plus US irradiation enhanced the tumor level of gene expression to a significantly high extent compared with the cationized dextran-plasmid DNA complex and free plasmid DNA with or without US irradiation. The enhanced level depended on the time period and timing of US irradiation. Fluorescent microscopic studies revealed that the localization of plasmid DNA and the gene expression were observed in

  18. Different Effects of Three Selected Lactobacillus Strains in Dextran Sulfate Sodium-Induced Colitis in BALB/c Mice.

    PubMed

    Cui, Yi; Wei, Hongyun; Lu, Fanggen; Liu, Xiaowei; Liu, Deliang; Gu, Li; Ouyang, Chunhui

    2016-01-01

    To analyze the changes of different Lactobacillus species in ulcerative colitis patients and to further assess the therapeutic effects of selected Lactobacillus strains on dextran sulfate sodium (DSS)-induced experimental colitis in BALB/c mice. Forty-five active ulcerative colitis (UC) patients and 45 population-based healthy controls were enrolled. Polymerase chain reaction (PCR) amplification and real-time PCR were performed for qualitative and quantitative analyses, respectively, of the Lactobacillus species in UC patients. Three Lactobacillus strains from three species were selected to assess the therapeutic effects on experimental colitis. Sixty 8-week-old BALB/c mice were divided into six groups. The five groups that had received DSS were administered normal saline, mesalazine, L. fermentum CCTCC M206110 strain, L. crispatus CCTCC M206119 strain, or L. plantarum NCIMB8826 strain. We assessed the severity of colitis based on disease activity index (DAI), body weight loss, colon length, and histologic damage. The detection rate of four of the 11 Lactobacillus species decreased significantly (P < 0.05), and the detection rate of two of the 11 Lactobacillus species increased significantly (P < 0.05) in UC patients. Relative quantitative analysis revealed that eight Lactobacillus species declined significantly in UC patients (P < 0.05), while three Lactobacillus species increased significantly (P < 0.05). The CCTCC M206110 treatment group had less weight loss and colon length shortening, lower DAI scores, and lower histologic scores (P < 0.05), while the CCTCC M206119 treatment group had greater weight loss and colon length shortening, higher histologic scores, and more severe inflammatory infiltration (P < 0.05). NCIMB8826 improved weight loss and colon length shortening (P < 0.05) with no significant influence on DAI and histologic damage in the colitis model. Administration of an L. crispatus CCTCC M206119 supplement aggravated DSS-induced colitis. L

  19. Different Effects of Three Selected Lactobacillus Strains in Dextran Sulfate Sodium-Induced Colitis in BALB/c Mice

    PubMed Central

    Cui, Yi; Wei, Hongyun; Lu, Fanggen; Liu, Xiaowei; Liu, Deliang; Gu, Li; Ouyang, Chunhui

    2016-01-01

    Aim To analyze the changes of different Lactobacillus species in ulcerative colitis patients and to further assess the therapeutic effects of selected Lactobacillus strains on dextran sulfate sodium (DSS)-induced experimental colitis in BALB/c mice. Methods Forty-five active ulcerative colitis (UC) patients and 45 population-based healthy controls were enrolled. Polymerase chain reaction (PCR) amplification and real-time PCR were performed for qualitative and quantitative analyses, respectively, of the Lactobacillus species in UC patients. Three Lactobacillus strains from three species were selected to assess the therapeutic effects on experimental colitis. Sixty 8-week-old BALB/c mice were divided into six groups. The five groups that had received DSS were administered normal saline, mesalazine, L. fermentum CCTCC M206110 strain, L. crispatus CCTCC M206119 strain, or L. plantarum NCIMB8826 strain. We assessed the severity of colitis based on disease activity index (DAI), body weight loss, colon length, and histologic damage. Results The detection rate of four of the 11 Lactobacillus species decreased significantly (P < 0.05), and the detection rate of two of the 11 Lactobacillus species increased significantly (P < 0.05) in UC patients. Relative quantitative analysis revealed that eight Lactobacillus species declined significantly in UC patients (P < 0.05), while three Lactobacillus species increased significantly (P < 0.05). The CCTCC M206110 treatment group had less weight loss and colon length shortening, lower DAI scores, and lower histologic scores (P < 0.05), while the CCTCC M206119 treatment group had greater weight loss and colon length shortening, higher histologic scores, and more severe inflammatory infiltration (P < 0.05). NCIMB8826 improved weight loss and colon length shortening (P < 0.05) with no significant influence on DAI and histologic damage in the colitis model. Conclusions Administration of an L. crispatus CCTCC M206119 supplement aggravated

  20. Polyphenol-rich sorghum brans alter colon microbiota and impact species diversity and species richness after multiple bouts of dextran sodium sulfate-induced colitis.

    PubMed

    Ritchie, Lauren E; Sturino, Joseph M; Carroll, Raymond J; Rooney, Lloyd W; Azcarate-Peril, M Andrea; Turner, Nancy D

    2015-03-01

    The microbiota affects host health, and dysbiosis is involved in colitis. Sorghum bran influences butyrate concentrations during dextran sodium sulfate (DSS) colitis, suggesting microbiota changes. We aimed to characterize the microbiota during colitis, and ascertain if polyphenol-rich sorghum bran diets mitigate these effects. Rats (n = 80) were fed diets containing 6% fiber from cellulose, or Black (3-deoxyanthocyanins), Sumac (condensed tannins), or Hi Tannin black (both) sorghum bran. Inflammation was induced three times using 3% DSS for 48 h (40 rats, 2 week separation), and the microbiota characterized by pyrosequencing. The Firmicutes/Bacteroidetes ratio was higher in Cellulose DSS rats. Colonic injury negatively correlated with Firmicutes, Actinobacteria, Lactobacillales and Lactobacillus, and positively correlated with Unknown/Unclassified. Post DSS#2, richness was significantly lower in Sumac and Hi Tannin black. Post DSS#3 Bacteroidales, Bacteroides, Clostridiales, Lactobacillales and Lactobacillus were reduced, with no Clostridium identified. Diet significantly affected Bacteroidales, Bacteroides, Clostridiales and Lactobacillus post DSS#2 and #3. Post DSS#3 diet significantly affected all genus, including Bacteroides and Lactobacillus, and diversity and richness increased. Sumac and Hi Tannin black DSS had significantly higher richness compared to controls. Thus, these sorghum brans may protect against alterations observed during colitis including reduced microbial diversity and richness, and dysbiosis of Firmicutes/Bacteroidetes. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Role of α-lipoic acid in dextran sulfate sodium-induced ulcerative colitis in mice: studies on inflammation, oxidative stress, DNA damage and fibrosis.

    PubMed

    Trivedi, P P; Jena, G B

    2013-09-01

    Ulcerative colitis affects many people worldwide. Inflammation and oxidative stress play a vital role in its pathogenesis. Previously, we reported that ulcerative colitis leads to systemic genotoxicity in mice. The present study was aimed at elucidating the role of α-lipoic acid in ulcerative colitis-associated local and systemic damage in mice. Experimental colitis was induced using 3%w/v dextran sulfate sodium in drinking water for 2 cycles. α-Lipoic acid was administered in a co-treatment (20, 40, 80 mg/kg bw) and post-treatment (80 mg/kg bw) schedule. Various biochemical parameters, histological evaluation, comet and micronucleus assays, immunohistochemistry and western blot analysis were employed to evaluate the effect of α-lipoic acid in mice with ulcerative colitis. The protective effect of α-lipoic acid was mediated through the modulation of nuclear factor kappa B, cyclooxygenase-2, interleukin 17, signal transducer and activator of transcription 3, nuclear erythroid 2-related factor 2, NADPH: quinone oxidoreductase-1, matrix metalloproteinase-9 and connective tissue growth factor. Further, ulcerative colitis led to an increased gut permeability, plasma lipopolysaccharide level, systemic inflammation and genotoxicity in mice, which was reduced with α-lipoic acid treatment. The present study identifies the underlying mechanisms involved in α-lipoic acid-mediated protection against ulcerative colitis and the associated systemic damage in mice. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. 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.

  3. Dextran: Influence of Molecular Weight in Antioxidant Properties and Immunomodulatory Potential.

    PubMed

    Soeiro, Vinicius C; Melo, Karoline R T; Alves, Monique G C F; Medeiros, Mayara J C; Grilo, Maria L P M; Almeida-Lima, Jailma; Pontes, Daniel L; Costa, Leandro S; Rocha, Hugo A O

    2016-08-19

    Dextrans (α-d-glucans) extracted from Leuconostoc mesenteroides, with molecular weights (MW) of 10 (D10), 40 (D40) and 147 (D147) kDa, were evaluated as antioxidant, anticoagulant and immunomodulatory drugs for the first time. None presented anticoagulant activity. As for the antioxidant and immunomodulatory tests, a specific test showed an increase in the dextran activity that was proportional to the increase in molecular weight. In a different assay, however, activity decreased or showed no correlation to the MW. As an example, the reducing power assay showed that D147 was twice as potent as other dextrans. On the other hand, all three samples showed similar activity (50%) when it came to scavenging the OH radical, whereas only the D10 sample showed sharp activity (50%) when it came to scavenging the superoxide ion. D40 was the single dextran that presented with immunomodulatory features since it stimulated the proliferation (~50%) of murine macrophages (RAW 264.7) and decreased the release of nitric oxide (~40%) by the cells, both in the absence and presence of lipopolysaccharides (LPS). In addition, D40 showed a greater scavenging activity (50%) for the hydrogen peroxide, which caused it to also be the more potent dextran when it came to inhibiting lipid peroxidation (70%). These points toward dextrans with a 40 kDa weight as being ideal for antioxidant and immunomodulatory use. However, future studies with the D40 and other similarly 40 kDa dextrans are underway to confirm this hypothesis.

  4. Dextran: Influence of Molecular Weight in Antioxidant Properties and Immunomodulatory Potential

    PubMed Central

    Soeiro, Vinicius C.; Melo, Karoline R. T.; Alves, Monique G. C. F.; Medeiros, Mayara J. C.; Grilo, Maria L. P. M.; Almeida-Lima, Jailma; Pontes, Daniel L.; Costa, Leandro S.; Rocha, Hugo A. O.

    2016-01-01

    Dextrans (α-d-glucans) extracted from Leuconostoc mesenteroides, with molecular weights (MW) of 10 (D10), 40 (D40) and 147 (D147) kDa, were evaluated as antioxidant, anticoagulant and immunomodulatory drugs for the first time. None presented anticoagulant activity. As for the antioxidant and immunomodulatory tests, a specific test showed an increase in the dextran activity that was proportional to the increase in molecular weight. In a different assay, however, activity decreased or showed no correlation to the MW. As an example, the reducing power assay showed that D147 was twice as potent as other dextrans. On the other hand, all three samples showed similar activity (50%) when it came to scavenging the OH radical, whereas only the D10 sample showed sharp activity (50%) when it came to scavenging the superoxide ion. D40 was the single dextran that presented with immunomodulatory features since it stimulated the proliferation (~50%) of murine macrophages (RAW 264.7) and decreased the release of nitric oxide (~40%) by the cells, both in the absence and presence of lipopolysaccharides (LPS). In addition, D40 showed a greater scavenging activity (50%) for the hydrogen peroxide, which caused it to also be the more potent dextran when it came to inhibiting lipid peroxidation (70%). These points toward dextrans with a 40 kDa weight as being ideal for antioxidant and immunomodulatory use. However, future studies with the D40 and other similarly 40 kDa dextrans are underway to confirm this hypothesis. PMID:27548151

  5. Semi-quantitative assessments of dextran toxicity on corneal endothelium: conceptual design of a predictive algorithm.

    PubMed

    Filev, Filip; Oezcan, Ceprail; Feuerstacke, Jana; Linke, Stephan J; Wulff, Birgit; Hellwinkel, Olaf J C

    2017-03-01

    Dextran is added to corneal culture medium for at least 8 h prior to transplantation to ensure that the cornea is osmotically dehydrated. It is presumed that dextran has a certain toxic effect on corneal endothelium but the degree and the kinetics of this effect have not been quantified so far. We consider that such data regarding the toxicity of dextran on the corneal endothelium could have an impact on scheduling and logistics of corneal preparation in eye banking. In retrospective statistic analyses, we compared the progress of corneal endothelium (endothelium cell loss per day) of 1334 organ-cultured corneal explants in media with and without dextran. Also, the influence of donor-age, sex and cause of death on the observed dextran-mediated effect on endothelial cell counts was studied. Corneas cultured in dextran-free medium showed a mean endothelium cell count decrease of 0.7% per day. Dextran supplementation led to a mean endothelium cell loss of 2.01% per day; this reflects an increase by the factor of 2.9. The toxic impact of dextran was found to be time dependent; while the prevailing part of the effect was observed within the first 24 h after dextran-addition. Donor age, sex and cause of death did not seem to have an influence on the dextran-mediated toxicity. Based on these findings, we could design an algorithm which approximately describes the kinetics of dextran-toxicity. We reproduced the previously reported toxic effect of dextran on the corneal endothelium in vitro. Additionally, this is the first work that provides an algorithmic instrument for the semi-quantitative calculation of the putative endothelium cell count decrease in dextran containing medium for a given incubation time and could thus influence the time management and planning of corneal transplantations.

  6. Injectable dextran hydrogels fabricated by metal-free click chemistry for cartilage tissue engineering.

    PubMed

    Wang, Xiaoyu; Li, Zihan; Shi, Ting; Zhao, Peng; An, Kangkang; Lin, Chao; Liu, Hongwei

    2017-04-01

    Injectable dextran-based hydrogels were prepared for the first time by bioorthogonal click chemistry for cartilage tissue engineering. Click-crosslinked injectable hydrogels based on cyto-compatible dextran (Mw=10kDa) were successfully fabricated under physiological conditions by metal-free alkyne-azide cycloaddition (click) reaction between azadibenzocyclooctyne-modified dextran (Dex-ADIBO) and azide-modified dextran (Dex-N 3 ). Gelation time of these dextran hydrogels could be regulated in the range of approximately 1.1 to 10.2min, depending on the polymer concentrations (5% or 10%) and ADIBO substitution degree (DS, 5 or 10) of Dex-ADIBO. Rheological analysis indicated that the dextran hydrogels were elastic and had storage moduli from 2.1 to 6.0kPa with increasing DS of ADIBO from 5 to 10. The in vitro tests revealed that the dextran hydrogel crosslinked from Dex-ADIBO DS 10 and Dex-N 3 DS 10 at a polymer concentration of 10% could support high viability of individual rabbit chondrocytes and the chondrocyte spheroids encapsulated in the hydrogel over 21days. Individual chondrocytes and chondrocyte spheroids in the hydrogel could produce cartilage matrices such as collagen and glycosaminoglycans. However, the chondrocyte spheroids produced a higher content of matrices than individual chondrocytes. This study indicates that metal-free click chemistry is effective to produce injectable dextran hydrogels for cartilage tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Self-degradation of tissue adhesive based on oxidized dextran and poly-L-lysine.

    PubMed

    Matsumura, Kazuaki; Nakajima, Naoki; Sugai, Hajime; Hyon, Suong-Hyu

    2014-11-26

    We have developed a low-toxicity bioadhesive based on oxidized dextran and poly-L-lysine. Here, we report that the mechanical properties and degradation of this novel hydrogel bioadhesive can be controlled by changing the extent of oxidation of the dextran and the type or concentration of the anhydride species in the acylated poly-L-lysine. The dynamic moduli of the hydrogels can be controlled from 120 Pa to 20 kPa, suggesting that they would have mechanical compatibility with various tissues, and could have applications as tissue adhesives. Development of the hydrogel color from clear to brown indicates that the reaction between the dextran aldehyde groups and the poly-L-lysine amino groups may be induced by a Maillard reaction via Schiff base formation. Degradation of the aldehyde dextran may begin by reaction of the amino groups in the poly-L-lysine. The gel degradation can be ascribed to degradation of the aldehyde dextran in the hydrogel, although the aldehyde dextran itself is relatively stable in water. The oxidized dextran and poly-L-lysine, and the degraded hydrogel showed low cytotoxicities. These findings indicate that a hydrogel consisting of oxidized dextran and poly-L-lysine has low toxicity and a well-controlled degradation rate, and has potential clinical applications as a bioadhesive. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Electron-beam generated porous dextran gels: experimental and quantum chemical studies.

    PubMed

    Naumov, Sergej; Knolle, Wolfgang; Becher, Jana; Schnabelrauch, Matthias; Reichelt, Senta

    2014-06-01

    The aim of this work was to investigate the reaction mechanism of electron-beam generated macroporous dextran cryogels by quantum chemical calculation and electron paramagnetic resonance measurements. Electron-beam radiation was used to initiate the cross-linking reaction of methacrylated dextran in semifrozen aqueous solutions. The pore morphology of the resulting cryogels was visualized by scanning electron microscopy. Quantum chemical calculations and electron paramagnetic resonance studies provided information on the most probable reaction pathway and the chain growth radicals. The most probable reaction pathway was a ring opening reaction and the addition of a C-atom to the double-bond of the methacrylated dextran molecule. First detailed quantum chemical calculation on the reaction mechanism of electron-beam initiated cross-linking reaction of methacrylated dextran are presented.

  9. Preparation and Characteristic of Dextran-BSA Antibody and Establishment of its ELISA Immunoassay.

    PubMed

    Xie, Zhen-ming; Yu, Lin; Fang, Li-sha

    2015-01-01

    The enzyme-linked immunosorbent assay (ELISA) is a potential tool for the determination of dextran. In this study, dextran neoglycoprotein antigens were prepared by Reductive Amination method, and were confirmed by SDS-PAGE and free amino detection. The impact factors such as different oxidation degree of dextran, the conjugate reaction time to BSA were investigated. The best preparation conditions were obtained (n(dextran)/n(oxidant) of NaIO4 = 1/120, the reaction time of 24 h), and the antigen with best combination with standard was obtained. The antigens interacted with standard antibody and were evaluated through ELISA. The immunogen was immunized with white rabbits to obtained antibody, respectively. A general and broad class-specific ELISA immunoassay was developed for dextran detection according to ELISA theory. The optimized conditions of assay used coating antigen at 10 μg/mL, reaction time of antibody and rabbit-anti-bovine IgG in 45 min, blocking reagents with 5% calf serum. The developed ELISA detection method with good linear and accuracy was put to use for quantitative analysis of dextran T40 in commercial sugarpractical for detection of dextran.

  10. Molecular weight kinetics and chain scission models for dextran polymers during ultrasonic degradation.

    PubMed

    Pu, Yuanyuan; Zou, Qingsong; Hou, Dianzhi; Zhang, Yiping; Chen, Shan

    2017-01-20

    Ultrasonic degradation of six dextran samples with different initial molecular weights (IMW) has been performed to investigate the degradation behavior and chain scission mechanism of dextrans. The weight-average molecular weight (Mw) and polydispersity index (D value) were monitored by High Performance Gel Permeation Chromatography (HPGPC). Results showed that Mw and D value decreased with increasing ultrasonic time, resulting in a more homologous dextran solution with lower molecular weight. A significant degradation occurred in dextrans with higher IMW, particularly at the initial stage of the ultrasonic treatment. The Malhotra model was found to well describe the molecular weight kinetics for all dextran samples. Experimental data was fitted into two chain scission models to study dextran chain scission mechanism and the model performance was compared. Results indicated that the midpoint scission model agreed well with experimental results, with a linear regression factor of R 2 >0.99. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Slow Sodium: An Oral Slowly Released Sodium Chloride Preparation

    PubMed Central

    Clarkson, E. M.; Curtis, J. R.; Jewkes, R. J.; Jones, B. E.; Luck, V. A.; de Wardener, H. E.; Phillips, N.

    1971-01-01

    The use of a slowly released oral preparation of sodium chloride is described. It was given to patients and athletes to treat or prevent acute and chronic sodium chloride deficiency. Gastrointestinal side effects were not encountered after the ingestion of up to 500 mEq in one day or 200 mEq in 10 minutes. PMID:5569979

  12. Electrogastrography in experimental pigs: the influence of gastrointestinal injury induced by dextran sodium sulphate on porcine gastric erythromycin-stimulated myoelectric activity.

    PubMed

    Tachecí, Ilja; Kvetina, Jaroslav; Kunes, Martin; Edakkanambeth Varayil, Jithinraj; Ali, Shahzad Marghoob; Pavlik, Michal; Kopacova, Marcela; Rejchrt, Stanislav; Bures, Jan; Pleskot, Miloslav

    2011-01-01

    Electrogastrography (EGG) is a non-invasive investigation of gastric myoelectrical activity. The aim of study was to evaluate the impact of erythromycin on EGG in gastrointestinal toxic injury induced by dextran sodium sulphate (DSS) in experimental pigs. The experiments were carried out on 12 adult pigs (weighing 30-35 kg). EGG was recorded using Digitrapper equipment (Synectics Medical AB, Stockholm). Running spectrum activity was used for EGG evaluation. There were two groups of animals: Group I: 6 controls with erythromycin administration (1,600 mg intragastrically); Group II: 6 animals treated with DSS (for 5 days, 0.25 g/kg per day in a dietary bolus) followed by erythromycin administration. Baseline and subsequent six separate 30-minute EGG-recordings (from time 0 to 360 min) were accomplished in each animal. A total of 84 records were analysed. Baseline dominant frequency of slow waves was fully comparable in both groups. In Group I, there was a significant increase in dominant frequency after erythromycin administration (maximum between 240-360 min). There was a flat non-significant and delayed increase in dominant frequency after erythromycin administration in Group II. The difference between Group I and II at particular time intervals was not significant but a diverse trend was evident. EGG recording enables us to register a gastric myoelectrical effect of prokinetic drugs. Erythromycin induced a significant increase in the dominant frequency of slow waves. DSS caused toxic injury to the porcine gastrointestinal tract responsible for the delayed and weaker myoelectrical effect of erythromycin in experimental animals.

  13. When to increase or reduce sodium loading in the management of fluid volume status during acute decompensated heart failure.

    PubMed

    Hirotani, Shinichi; Masuyama, Tohru

    2014-12-01

    Sodium restriction has been believed to be indispensible to manage fluid overload during acute decompensated heart failure (ADHF). However, recently, it was reported that a change in aggression of sodium and water restriction did not affect the outcome of ADHF. In contrast, current data suggest that small amount of hypertonic saline solution with high-dose furosemide produces an improvement in haemodynamic and clinical parameters without any severe adverse effects. In this perspective, first, we are going to describe the effects of sodium loading on neurohormonal activation, body's sodium balance, and renal function in chronic heart failure and the efficacy of loop diuretics in ADHF. Then, we are going to explain the possible mechanisms by which sodium loading enhances the efficacy of loop diuretics and about the clinical conditions during which sodium loading should be avoided. © 2014 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

  14. 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

  15. 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.

  16. 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.

  17. Engineering dextran-based scaffolds for drug delivery and tissue repair

    PubMed Central

    Sun, Guoming; Mao, Jeremy J

    2015-01-01

    Owing to its chemically reactive hydroxyl groups, dextran can be modified with different functional groups to form spherical, tubular and 3D network structures. The development of novel functional scaffolds for efficient controlled release and tissue regeneration has been a major research interest, and offers promising therapeutics for many diseases. Dextran-based scaffolds are naturally biodegradable and can serve as bioactive carriers for many protein biomolecules. The reconstruction of the in vitro microenvironment with proper signaling cues for large-scale tissue regenerative scaffolds has yet to be fully developed, and remains a significant challenge in regenerative medicine. This paper will describe recent advances in dextran-based polymers and scaffolds for controlled release and tissue engineering. Special attention is given to the development of dextran-based hydrogels that are precisely manipulated with desired structural properties and encapsulated with defined angiogenic growth factors for therapeutic neovascularization, as well as their potential for wound repair. PMID:23210716

  18. Effect of Sulfation and Molecular Weight on Anticoagulant Activity of Dextran.

    PubMed

    Drozd, N N; Logvinova, Yu S; Torlopov, M A; Udoratina, E V

    2017-02-01

    Sulfation (to 2.8) of dextrans with molecular weight of 150 and 20 kDa was followed by the appearance of anticoagulant activity that increased with decreasing their molecular weight and did not depend on antithrombin, plasma inhibitor of serine proteases of the blood coagulation system. Antithrombin activity of dextran sulfate with a molecular weight of 20 kDa reached 12.6-15.3 U/mg. Dextran sulfates with molecular weights of 20 and 150 kDa did not potentiate ADP-induced human platelet aggregation.

  19. Low molecular weight dextran provides similar optical coherence tomography coronary imaging compared to radiographic contrast media.

    PubMed

    Frick, Kyle; Michael, Tesfaldet T; Alomar, Mohammed; Mohammed, Atif; Rangan, Bavana V; Abdullah, Shuaib; Grodin, Jerrold; Hastings, Jeffrey L; Banerjee, Subhash; Brilakis, Emmanouil S

    2014-11-01

    Optical coherence tomography (OCT) coronary imaging requires displacement of red blood cells from the vessel lumen. This is usually accomplished using radiographic contrast. Low molecular weight dextran has low cost and is safe in low volumes. In the present study, we compared dextran with contrast for coronary OCT imaging. Fifty-one vessels in 26 patients were sequentially imaged using manual injection of radiographic contrast (iodixanol) and dextran. OCT images were analyzed at 1 mm intervals to determine the image clarity (defined as a visible lumen border > 270°) and to measure the lumen area and lumen diameter. To correct for the refractive index of dextran, the dextran area measurements were multiplied by 1.117 and the dextran length measurements were multiplied by 1.057. A total of 3,418 cross-sections (1,709 with contrast and 1,709 with dextran) were analyzed. There were no complications related to OCT imaging or to contrast or dextran administration. Clear image segments were observed in 97.0% vs. 96.7% of the cross-sections obtained with contrast and dextran, respectively (P = 0.45). The mean lumen areas were also similar: 6.69 ± 1.95 mm(2) with iodixanol vs. 7.06 ± 2.06 mm(2) with dextran (correlation coefficient 0.984). The image quality and measurements during OCT image acquisition are similar for dextran and contrast. Dextran could be used instead of contrast for OCT imaging, especially in patients in whom contrast load minimization is desired. © 2013 Wiley Periodicals, Inc.

  20. Sodium bicarbonate supplementation improves severe-intensity intermittent exercise under moderate acute hypoxic conditions.

    PubMed

    Deb, Sanjoy K; Gough, Lewis A; Sparks, S Andy; McNaughton, Lars R

    2018-03-01

    Acute moderate hypoxic exposure can substantially impair exercise performance, which occurs with a concurrent exacerbated rise in hydrogen cation (H + ) production. The purpose of this study was therefore, to alleviate this acidic stress through sodium bicarbonate (NaHCO 3 ) supplementation and determine the corresponding effects on severe-intensity intermittent exercise performance. Eleven recreationally active individuals participated in this randomised, double-blind, crossover study performed under acute normobaric hypoxic conditions (FiO 2 % = 14.5%). Pre-experimental trials involved the determination of time to attain peak bicarbonate anion concentrations ([HCO 3 - ]) following NaHCO 3 ingestion. The intermittent exercise tests involved repeated 60-s work in their severe-intensity domain and 30-s recovery at 20 W to exhaustion. Participants ingested either 0.3 g kg bm -1 of NaHCO 3 or a matched placebo of 0.21 g kg bm -1 of sodium chloride prior to exercise. Exercise tolerance (+ 110.9 ± 100.6 s; 95% CI 43.3-178 s; g = 1.0) and work performed in the severe-intensity domain (+ 5.8 ± 6.6 kJ; 95% CI 1.3-9.9 kJ; g = 0.8) were enhanced with NaHCO 3 supplementation. Furthermore, a larger post-exercise blood lactate concentration was reported in the experimental group (+ 4 ± 2.4 mmol l -1 ; 95% CI 2.2-5.9; g = 1.8), while blood [HCO 3 - ] and pH remained elevated in the NaHCO 3 condition throughout experimentation. In conclusion, this study reported a positive effect of NaHCO 3 under acute moderate hypoxic conditions during intermittent exercise and therefore, may offer an ergogenic strategy to mitigate hypoxic induced declines in exercise performance.

  1. Amphipathic dextran-doxorubicin prodrug micelles for solid tumor therapy.

    PubMed

    Jin, Rong; Guo, Xuelian; Dong, Lingli; Xie, Enyuan; Cao, Aoneng

    2017-10-01

    A group of micelles self-assembled from deoxycholic acid-doxorubicin-conjugated dextran (denoted as Dex-DCA-DOX) prodrugs were designed and prepared for pH-triggered drug release and cancer chemotherapy. These prodrugs could be successfully produced by chemically coupling hydrophobic deoxycholic acid (DCA) to dextran hydrazine (denoted as Dex-NHNH 2 ) and hydrazone linker formation between doxorubicin (DOX) and Dex-NHNH 2 . These Dex-DCA-DOX prodrugs self-assembled to form micelles under physiological conditions with varied particle sizes depending on molecular weight of dextran, degree of substitution (DS) of DCA and DOX. After optimization, Dex10k-DCA9-DOX5.5 conjugate comprising dextran of 10kDa, DCA of DS 9 and DOX loading content of 5.5wt%, formed the micelles with the smallest size (110nm). These prodrug micelles could slowly liberate DOX under physiological conditions but efficiently released the drug at an acidified endosomal pH by the hydrolysis of acid-labile hydrazone linker. In vitro cytotoxicity experiment indicated that Dex10k-DCA9-DOX5.5 micelles exerted marked antitumor activity against MCF-7 and SKOV-3 cancer cells. Besides, intravenous administration of the micelles afforded growth inhibition of SKOV-3 tumor bearing in nude mice at a dosage of 2.5mg per kg with anti-cancer efficacy comparable to free DOX-chemotherapy but low systemic toxicity. This study highlights the feasibility of bio-safe and efficient dextran-based prodrug micelles designed for cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Correlation of transarterial transport of various dextrans with their physicochemical properties.

    PubMed

    Elmalak, O; Lovich, M A; Edelman, E

    2000-11-01

    Local vascular drug delivery provides elevated concentrations of drug in the target tissue while minimizing systemic side effects. To better characterize local pharmacokinetics we examined the arterial transport of locally applied dextran and dextran derivatives in vivo. Using a two-compartment pharmacokinetic model to correct the measured transmural flux of these compounds for systemic redistribution and elimination as delivered from a photopolymerizable hydrogel surrounding rat carotid arteries, we found that the diffusivities and the transendothelial permeabilities were strongly dependent on molecular weight and charge. For neutral dextrans, the effective diffusive resistance in the media increased with molecular weight approximately 4.1-fold between the molecular weights of 10 and 282 kDa. Similarly, endothelial resistance increased 28-fold over the same molecular weight range. The effective medial diffusive resistance was unaffected by cationic charge as such molecules moved identically to neutral compounds, but increased approximately 40% when dextrans were negatively charged. Transendothelial resistance was 20-fold lower for the cationic dextrans, and 11-fold higher for the anionic dextrans, when both were compared to neutral counterparts. These results suggest that, while low molecular weight drugs will rapidly traverse the arterial wall with the endothelium posing a minimal barrier, the reverse is true for high molecular weight agents. With these data, the deposition and distribution of locally released vasotherapeutic compounds might be predicted based upon chemical properties, such as molecular weight and charge.

  3. The effect of the size of fluorescent dextran on its endocytic pathway.

    PubMed

    Li, Lei; Wan, Tao; Wan, Min; Liu, Bei; Cheng, Ran; Zhang, Rongying

    2015-05-01

    Fluorescent dextrans are commonly used as macropinocytic probes to study the properties of endocytic cargoes; however, the effect of the size of dextrans on endocytic mechanisms has not been carefully analyzed. By using chemical and siRNA inhibition of individual endocytic pathways, we evaluated the internalization of two commonly used dextrans, Dex10 (dextran 10 kDa) and Dex70 (dextran 70 kDa), in mammalian HeLa cells and Caenorhabditis elegans coelomocytes. We revealed that Dex70 enters these two cell types predominantly via clathrin- and dynamin-independent and amiloride-sensitive macropinocytosis process; Dex10, on the other hand, enters the two cell types through clathrin-/dynamin-dependent micropinocytosis in addition to macropinocytosis. In addition, although different-sized dextrans follow different endocytic processes, they share common post-endocytic events. Herein, though straightforward, our studies support that the size of nanomaterials could play a paramount role in their inclusion into endocytic vesicles and suggest that care should be taken while selecting endocytic pathway markers. Based on our results, we propose that Dex70 is a better probe for macropinocytosis, whereas Dex10 and smaller molecules are better for probing general fluid-phase endocytosis, which includes macropinocytic and micropinocytic processes. © 2015 International Federation for Cell Biology.

  4. Crystallization and preliminary X-ray analysis of Streptococcus mutans dextran glucosidase

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

    Saburi, Wataru; Hondoh, Hironori, E-mail: hondoh@abs.agr.hokudai.ac.jp; Unno, Hideaki

    2007-09-01

    Dextran glucosidase from S. mutans was crystallized using the hanging-drop vapour-diffusion method. The crystals diffracted to 2.2 Å resolution. Dextran glucosidase from Streptococcus mutans is an exo-hydrolase that acts on the nonreducing terminal α-1,6-glucosidic linkage of oligosaccharides and dextran with a high degree of transglucosylation. Based on amino-acid sequence similarity, this enzyme is classified into glycoside hydrolase family 13. Recombinant dextran glucosidase was purified and crystallized by the hanging-drop vapour-diffusion technique using polyethylene glycol 6000 as a precipitant. The crystals belong to the orthorhombic space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 72.72, b = 86.47, cmore » = 104.30 Å. A native data set was collected to 2.2 Å resolution from a single crystal.« less

  5. Transfection using DEAE-dextran.

    PubMed

    Selden, R F

    2001-05-01

    Two protocols for DEAE-dextran transfection of cells are provided in this unit. The Basic Protocol describes a procedure used to transfect adherent cells and the first Alternate Protocol presents a method used to transfect suspension cells. If an increase in transfection efficiency is needed, cells can be treated with chloroquine as described in the second Alternate Protocol.

  6. Comparative study of flux of FITC-labeled Dextran 4000 on normal (iso)- and hyper-osmolarity in basal side in caco-2 cell monolayers.

    PubMed

    Ohkubo, Rie; Tomita, Mikio; Hotta, Yoshiyuki; Nagira, Mayuko; Hayashi, Masahiro

    2003-01-01

    We have shown previously that the flux of fluorescein isothiocyanate dextran 4000 (FD-4) is transported across the Caco-2 cell monolayers in a polarized fashion favoring the basal to apical direction under normal conditions (i.e., isotonic solution in basal side). Furthermore, FD-4 transport may occur via a process that included a certain degree of substrate specificity for polysaccharide and transcytosis. In the present study, we compared the flux of FD-4 in the basal to apical direction (efflux) and the apical to basal direction (influx) in stress conditions (i.e., hyperosmolarity in basal side) to those in normal conditions (i.e., iso-osmolarity in basal side). The efflux of FD-4 was increased by hyperosmolarity in basal side, but the influx was decreased when compared with normal conditions. Neither dextran 10, 000 nor colchicine inhibited the efflux of FD-4 in hyperosmolarity conditions. The inhibition of efflux of FD-4 was observed not by S-nitroso-N-acetylpenicillamine but by sodium nitroprusside and sodium ferrocyanide. These results collectively suggest that hyperosmolarity in basal side accelerates the efflux of FD-4 across the transcellular route but not across the paracellular route in Caco-2 cell monolayers. And it is indicated that cyanide rather than nitric oxide is involved in dysfunction of the FD-4 efflux system irrespective of conditions such as normal osmolarity or hyperosmolarity.

  7. Use of dextran nanoparticle: A paradigm shift in bacterial exopolysaccharide based biomedical applications.

    PubMed

    Banerjee, Aparna; Bandopadhyay, Rajib

    2016-06-01

    This review is a concise compilation of all the major researches on dextran nanoparticle based biomedical applications. Dextran is a highly biocompatible and biodegradable neutral bacterial exopolysaccharide with simple repeating glucose subunits. It's simple yet unique biopolymeric nature made it highly suitable as nanomedicine, nanodrug carrier, and cell imaging system or nanobiosensor. Most importantly, it is extremely water soluble and shows no post drug delivery cellular toxicity. Complete metabolism of dextran is possible inside body thus possibility of renal failure is minimum. Dextran based nanoparticles have superior aqueous solubility, high cargo capacity and intrinsic viscosity, and short storage period. The main focus area of this review is- past and present of major biomedical applications of dextran based nanomaterials thus showing a paradigm shift in bacterial exopolysaccharide based nanobiotechnology. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Functional food applications of dextran from Weissella cibaria RBA12 from pummelo (Citrus maxima).

    PubMed

    Baruah, Rwivoo; Maina, Ndegwa H; Katina, Kati; Juvonen, Riikka; Goyal, Arun

    2017-02-02

    Weissella cibaria RBA12 isolated from pummelo from Northeast India produces a dextran composed of 97% α-(1→6) linkages in the main chain and 3% α-(1→3) branched linkages. The in vitro prebiotic activity of dextran-RBA12 was explored. Dextran-RBA12 displayed enhanced growth of probiotic Bifidobacterium and Lactobacillus spp., and controlled growth of non-probiotic enteric bacteria. Dextran-RBA12 showed superior resistance to physiological barriers with a maximum hydrolysis of 0.51%, 0.31% and 0.24% by artificial gastric juice, α-amylase and intestinal fluid, respectively, whereas compared to maximum hydrolysis of 25.23%, 19.13% and 6%, respectively after 5h of incubation shown by commercial prebiotic inulin. The production of dextran from Weissella cibaria RBA12 in sourdough prepared from whole wheat flour, wheat bran and rye bran showed the highest dextran of 3.26±0.12% d.w. in rye bran. The overall study summarized that dextran-RBA12 can be used as a prebiotic and also can be easily produced in sourdough. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. (Quasi-) 2D aggregation of polystyrene-b-dextran at the air-water interface.

    PubMed

    Bosker, Wouter T E; Cohen Stuart, Martien A; Norde, Willem

    2013-02-26

    Polystyrene-b-dextran (PS-b-Dextran) copolymers can be used to prepare dextran brushes at solid surfaces, applying Langmuir-Blodgett deposition. When recording the interfacial pressure versus area isotherms of a PS-b-Dextran monolayer, time-dependent hysteresis was observed upon compression and expansion. We argue that this is due to (quasi-) 2D aggregation of the copolymer at the air-water surface, with three contributions. First, at large area per molecule, a zero surface pressure is measured; we ascribe this to self-assembly of block copolymers into surface micelles. At intermediate area we identify a second regime ("desorption regime") where aggregation into large patches occurs due to van der Waals attraction between PS blocks. At high surface pressure ("brush regime") we observe hysteretic behavior attributed to H-bonding between dextran chains. When compared to hysteresis of other amphiphilic diblock copolymers (also containing PS, e.g., polystyrene-b-poly(ethylene oxide)) a general criterion can be formulated concerning the extent of hysteresis: when the hydrophobic (PS) block is of equal size as (or bigger than) the hydrophilic block, the hysteresis is maximal. The (quasi-) 2D aggregation of PS-b-Dextran has significant implications for the preparation of dextran brushes at solid surfaces using Langmuir-Blodgett deposition. For each grafting density the monolayer needs to relax, up to several hours, prior to transfer.

  10. Enteric-coated mycophenolate sodium.

    PubMed

    Gabardi, Steven; Tran, Jennifer L; Clarkson, Michael R

    2003-11-01

    To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium. Primary literature was obtained via a MEDLINE search (1966-June 2003). Abstracts were obtained from the manufacturer and included in the analysis. All studies and abstracts evaluating mycophenolate sodium in solid organ transplantation were considered for inclusion. English-language studies and abstracts were selected for inclusion, but were limited to those consisting of human subjects. Mycophenolate sodium, a mycophenolic acid prodrug, is an inhibitor of T-lymphocyte proliferation. Mycophenolic acid reduces the incidence of acute rejection in renal transplantation. Mycophenolate sodium is enteric coated and has been suggested as a potential method to reduce the gastrointestinal adverse events seen with mycophenolate mofetil. Both mycophenolate mofetil and mycophenolate sodium have been shown to be therapeutically equivalent at decreasing the incidence of allograft rejection and loss. The frequency of adverse events is similar between both compounds, with the most common events being diarrhea and leukopenia. Mycophenolate sodium is effective in preventing acute rejection in renal transplant recipients. At doses of 720 mg twice daily, the efficacy and safety profiles are similar to those of mycophenolate mofetil 1000 mg twice daily. Mycophenolate sodium has been approved in Switzerland; approval in the US is pending.

  11. 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.

  12. 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.

  13. Superior prebiotic and physicochemical properties of novel dextran from Weissella cibaria JAG8 for potential food applications.

    PubMed

    Tingirikari, Jagan Mohan Rao; Kothari, Damini; Goyal, Arun

    2014-09-01

    The dextran produced by dextransucrase from Weissella cibaria JAG8 was subjected to physicochemical characterization and assessment of its prebiotic potential. Dextran displayed a solubility of 24.5% and a water holding capacity of 352%. The emulsion and flocculation activity of dextran were 89% and 92%, respectively. The degradation temperature (Td) of dextran was 353 °C. Dextran exhibited 33- and 12-fold less hydrolysis than inulin, in simulated gastric juice (pH 1.0) and α-amylase (pH 7.0), respectively. Dextran stimulated the growth of probiotic bacteria such as Bifidobacterium animalis subspecies lactis, Bifidobacterium infantis and Lactobacillus acidophilus significantly and was comparable to that of commercial inulin. However, the growth of E. coli was not enhanced by dextran or inulin. The dextran used in this study can be used as a potential prebiotic for health benefits.

  14. Roles of dextrans on improving lymphatic drainage for liposomal drug delivery system.

    PubMed

    Feng, Linglin; Zhang, Lei; Liu, Min; Yan, Zhiqiang; Wang, Chenyu; Gu, Bing; Liu, Yu; Wei, Gang; Zhong, Gaoren; Lu, Weiyue

    2010-04-01

    Our aim was to develop a novel liposomal drug delivery system containing dextrans to reduce undesirable retention of antineoplastic agents and thus alleviate local tissue damage. At the cell level, diethylaminoethyl-dextran (DEAE-Dx) showed the strongest inhibiting effect on liposome uptake by macrophages among tested dextrans. The distribution of radiolabeled liposomes mixed with dextrans in injection site and draining lymph node was investigated in rats after subcutaneous injection. DEAE-Dx substantially reduced the undesired local retention and promoted the draining of liposome into lymphatics, which was further confirmed by confocal microscopy images revealing the substantial prevention of rhodamine B-labelled liposome sequestration by macrophages in normal lymph node in rats. Pharmacokinetic data indicated the accelerated drainage of liposome through lymphatics back to systemic circulation by mixing with DEAE-Dx. In the toxicological study in rabbits, DEAE-Dx alleviated the local tissue damage caused by liposomal doxorubicin. In conclusion, dextrans, particularly DEAE-Dx, could efficiently enhanced liposomes drainage into lymphatics, which proves themselves as promising adjuvants for lymphatic-targeted liposomal drug delivery system.

  15. β-Cyclodextrin-dextran polymers for the solubilization of poorly soluble drugs.

    PubMed

    di Cagno, Massimiliano; Terndrup Nielsen, Thorbjørn; Lambertsen Larsen, Kim; Kuntsche, Judith; Bauer-Brandl, Annette

    2014-07-01

    The aim of this study was to assess the potential of novel β-cyclodextrin (βCD)-dextran polymers for drug delivery. The size distribution of βCD-dextrans (for eventual parenteral administration), the influence of the dextran backbones on the stability of the βCD/drug complex, the solubilization efficiency of poorly soluble drugs and drug release properties were investigated. Size analysis of different βCD-dextrans was measured by size exclusion chromatography (SEC) and asymmetrical flow field-flow fractionation (AF4). Stability of drug/βCD-dextrans was assessed by isothermal titration calorimetry (ITC) and molar enthalpies of complexation and equilibrium constants compared to some commercially available βCD derivatives. For evaluation of the solubilization efficiency, phase-solubility diagrams were made employing hydrocortisone (HC) as a model of poorly soluble drugs, whereas reverse dialysis was used to detect potential drug supersaturation (increased molecularly dissolved drug concentration) as well as controlled release effects. Results indicate that all investigated βCD-polymers are of appropriate sizes for parenteral administration. Thermodynamic results demonstrate that the presence of the dextran backbone structure does not affect the stability of the βCD/drug complex, compared to native βCD and commercially available derivatives. Solubility studies evidence higher solubilizing abilities of these new polymers in comparison to commercially available βCDs, but no supersaturation states were induced. Moreover, drug release studies evidenced that diffusion of HC was influenced by the solubilization induced by the βCD-derivatives. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Development of poly-l-lysine-coated calcium-alginate microspheres encapsulating fluorescein-labeled dextrans

    NASA Astrophysics Data System (ADS)

    Charron, Luc; Harmer, Andrea; Lilge, Lothar

    2005-09-01

    A technique to produce fluorescent cell phantom standards based on calcium alginate microspheres with encapsulated fluorescein-labeled dextrans is presented. An electrostatic ionotropic gelation method is used to create the microspheres which are then exposed to an encapsulation method using poly-l-lysine to trap the dextrans inside. Both procedures were examined in detail to find the optimal parameters producing cell phantoms meeting our requirements. Size distributions favoring 10-20 microns microspheres were obtained by varying the high voltage and needle size parameters. Typical size distributions of the samples were centered at 150 μm diameter. Neither the molecular weight nor the charge of the dextrans had a significant effect on their retention in the microspheres, though anionic dextrans were chosen to help in future capillary electrophoresis work. Increasing the exposure time of the microspheres to the poly-l-lysine solution decreased the leakage rates of fluorescein-labeled dextrans.

  17. Temperature-responsive electrospun nanofibers for ‘on–off’ switchable release of dextran

    PubMed Central

    Kim, Young-Jin; Ebara, Mitsuhiro; Aoyagi, Takao

    2012-01-01

    We propose a new type of ‘smart’ nanofiber (NF) with dynamically and reversibly tunable properties for the ‘on–off’ controlled release of the polysaccharide dextran. The fibers are produced by electrospinning copolymers of N-isopropylacrylamide (NIPAAm) and N-hydroxymethylacrylamide (HMAAm). The OH groups of HMAAm are subsequently crosslinked by thermal curing. The copolymers were successfully fabricated into a well-defined nanofibrous structure with a diameter of about 600–700 nm, and the fibers preserved their morphology even after thermal curing. The resulting crosslinked NFs showed rapid and reversible volume changes in aqueous media in response to cycles of temperature alternation. The fibrous morphology was maintained for the crosslinked NFs even after the cycles of temperature alternation, while non-crosslinked NFs collapsed and dispersed quickly in the aqueous solution. Dextran-containing NFs were prepared by electrospinning the copolymers blended with fluorescein isothiocyanate (FITC)-dextran, and the ‘on–off’ switchable release of FITC-dextran from the crosslinked NFs was observed. Almost all the FITC-dextran was released from the NFs after six heating cycles, whereas only a negligible amount of FITC-dextran was evolved during the cooling process. The reported incorporation of smart properties into NFs takes advantage of their extremely large surface area and porosity and is expected to provide a simple platform for on–off drug delivery. PMID:27877530

  18. Nanoparticles of alkylglyceryl-dextran-graft-poly(lactic acid) for drug delivery to the brain: Preparation and in vitro investigation.

    PubMed

    Toman, Petr; Lien, Chun-Fu; Ahmad, Zeeshan; Dietrich, Susanne; Smith, James R; An, Qian; Molnár, Éva; Pilkington, Geoffrey J; Górecki, Darek C; Tsibouklis, John; Barbu, Eugen

    2015-09-01

    Poly(lactic acid), which has an inherent tendency to form colloidal systems of low polydispersity, and alkylglyceryl-modified dextran - a material designed to combine the non-immunogenic and stabilising properties of dextran with the demonstrated permeation enhancing ability of alkylglycerols - have been combined for the development of nanoparticulate, blood-brain barrier-permeating, non-viral vectors. To this end, dextran, that had been functionalised via treatment with epoxide precursors of alkylglycerol, was covalently linked to poly(lactic acid) using a carbodiimide cross-linker to form alkylglyceryl-modified dextran-graft-poly(lactic acid). Solvent displacement and electrospray methods allowed the formulation of these materials into nanoparticles having a unimodal size distribution profile of about 100-200nm and good stability at physiologically relevant pH (7.4). The nanoparticles were characterised in terms of hydrodynamic size (by Dynamic Light Scattering and Nanoparticle Tracking Analysis), morphology (by Scanning Electron Microscopy and Atomic Force Microscopy) and zeta potential, and their toxicity was evaluated using MTT and PrestoBlue assays. Cellular uptake was evidenced by confocal microscopy employing nanoparticles that had been loaded with the easy-to-detect Rhodamine B fluorescent marker. Transwell-model experiments employing mouse (bEnd3) and human (hCMEC/D3) brain endothelial cells revealed enhanced permeation (statistically significant for hCMEC/D3) of the fluorescent markers in the presence of the nanoparticles. Results of studies using Electric Cell Substrate Impedance Sensing suggested a transient decrease of the barrier function in an in vitro blood-brain barrier model following incubation with these nanoformulations. An in ovo study using 3-day chicken embryos indicated the absence of whole-organism acute toxicity effects. The collective in vitro data suggest that these alkylglyceryl-modified dextran-graft-poly(lactic acid) nanoparticles

  19. 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.

  20. Substance-P alleviates dextran sulfate sodium-induced intestinal damage by suppressing inflammation through enrichment of M2 macrophages and regulatory T cells.

    PubMed

    Hong, Hyun Sook; Hwang, Dae Yeon; Park, Ju Hyeong; Kim, Suna; Seo, Eun Jung; Son, Youngsook

    2017-02-01

    Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease (IBD). Thus, regulation of inflammation is regarded as the ultimate therapy for intestinal disease. Substance-P (SP) is known to mediate proliferation, migration, and cellular senescence in a variety of cells. SP was found to mobilize stem cells from bone marrow to the site of injury and to suppress inflammatory responses by inducing regulatory T cells (Tregs) and M2 macrophages. In this study, we explored the effects of SP in a dextran sodium sulfate (DSS)-induced intestine damage model. The effects of SP were evaluated by analyzing crypt structures, proliferating cells within the colon, cytokine secretion profiles, and immune cells population in the spleen/mesenteric lymph nodes in vivo. DSS treatment provoked an inflammatory response with loss of crypts in the intestines of experimental mice. This response was associated with high levels of inflammatory cytokines such as TNF-α and IL-17, and low levels of Tregs and M2 macrophages, leading to severely damaged tissue structure. However, SP treatment inhibited inflammatory responses by modulating cytokine production as well as the balance of Tregs/Th 17 cells and the M1/M2 transition in lymphoid organs, leading to accelerated tissue repair. Collectively, our data indicate that SP can promote the regeneration of tissue following damage by DSS treatment, possibly by modulating immune response. Our results propose SP as a candidate therapeutic for intestine-related inflammatory diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Metallization and Biopatterning on Ultra-Flexible Substrates via Dextran Sacrificial Layers

    PubMed Central

    Tseng, Peter; Pushkarsky, Ivan; Di Carlo, Dino

    2014-01-01

    Micro-patterning tools adopted from the semiconductor industry have mostly been optimized to pattern features onto rigid silicon and glass substrates, however, recently the need to pattern on soft substrates has been identified in simulating cellular environments or developing flexible biosensors. We present a simple method of introducing a variety of patterned materials and structures into ultra-flexible polydimethylsiloxane (PDMS) layers (elastic moduli down to 3 kPa) utilizing water-soluble dextran sacrificial thin films. Dextran films provided a stable template for photolithography, metal deposition, particle adsorption, and protein stamping. These materials and structures (including dextran itself) were then readily transferrable to an elastomer surface following PDMS (10 to 70∶1 base to crosslinker ratios) curing over the patterned dextran layer and after sacrificial etch of the dextran in water. We demonstrate that this simple and straightforward approach can controllably manipulate surface wetting and protein adsorption characteristics of PDMS, covalently link protein patterns for stable cell patterning, generate composite structures of epoxy or particles for study of cell mechanical response, and stably integrate certain metals with use of vinyl molecular adhesives. This method is compatible over the complete moduli range of PDMS, and potentially generalizable over a host of additional micro- and nano-structures and materials. PMID:25153326

  2. Molar mass fractionation in aqueous two-phase polymer solutions of dextran and poly(ethylene glycol).

    PubMed

    Zhao, Ziliang; Li, Qi; Ji, Xiangling; Dimova, Rumiana; Lipowsky, Reinhard; Liu, Yonggang

    2016-06-24

    Dextran and poly(ethylene glycol) (PEG) in phase separated aqueous two-phase systems (ATPSs) of these two polymers, with a broad molar mass distribution for dextran and a narrow molar mass distribution for PEG, were separated and quantified by gel permeation chromatography (GPC). Tie lines constructed by GPC method are in excellent agreement with those established by the previously reported approach based on density measurements of the phases. The fractionation of dextran during phase separation of ATPS leads to the redistribution of dextran of different chain lengths between the two phases. The degree of fractionation for dextran decays exponentially as a function of chain length. The average separation parameters, for both dextran and PEG, show a crossover from mean field behavior to Ising model behavior, as the critical point is approached. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. 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

  4. 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.

  5. The Effects of Stereotactic Cerebroventricular Administration of Albumin, Mannitol, Hypertonic Sodium Chloride, Glycerin and Dextran in Rats with Experimental Brain Edema.

    PubMed

    Ates, Tuncay; Gezercan, Yurdal; Menekse, Guner; Turkoz, Yusuf; Parlakpinar, Hakan; Okten, Ali Ihsan; Akyuva, Yener; Onal, Selami Cagatay

    2017-01-01

    To evaluate the effects of cerebroventricular administration of hyperoncotic/hyperosmotic agents on edematous brain tissue in rats with experimental head trauma. The study included 54 female Sprague-Dawley rats with weights ranging between 200 and 250 g. Six experimental groups were examined with each group containing 9 rats. All rats were exposed to head trauma, and treatment groups were administered 2 µl of one of the drugs (albumin, mannitol, hypertonic sodium chloride (NaCl), glycerin and dextran) 6, 12 and 24 hours after the trauma via the cerebroventricular route and using a stereotactic device. Rats were sacrificed 48 hours after the trauma, and brain tissues were extracted without damage. Biochemical analyses including reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) were performed on the injured left hemisphere. Compared with the control group, the albumin, mannitol, 3% NaCl and glycerin treatment groups revealed dramatic increases in GSH levels (p < 0.001). Levels of MDA, which is the end-product of brain edema and lipid peroxidation, failed to show a statistically significant decrease, but there was a decreasing trend observed in the inter-group comparisons. NO levels were also decreased in the 3% NaCl treatment group. An analysis of TNF-α and IL-1β, two proinflammatory cytokines associated with the trauma, revealed that IL-1β decreased significantly in all treatment groups (p=0.001), whereas no significant difference was detected in TNF-α levels. Cerebroventricular administration of hyperoncotic/hyperosmotic agents provides substantial effects on the treatment of brain edema.

  6. 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

  7. Acute oral toxicity of sodium cyanide in birds

    USGS Publications Warehouse

    Wiemeyer, Stanley N.; Hill, E.F.; Carpenter, J.W.; Krynitsky, A.J.

    1986-01-01

    Sensitivities of six avian species, black vulture (Coragyps atratus), American kestrel (Falco sparverius), Japanese quail (Coturnix japonica), domestic chicken (Gallus domesticus), eastern screech-owl (Otus asio), and European starling (Sturnus vulgaris), to acute poisoning by sodium cyanide (NaCN) were compared by single dose LD50's. Three species, domestic chickens, black vultures, and turkey vultures (Cathartes aura), were dosed with NaCN to determine cyanide residues in those that died and also in survivors, in addition to postmortem fate. Three flesh-eating species (black vulture, American kestrel, and eastern screech-owl; LD50's 4.0-8.6 mg/kg) were more sensitive to NaCN than three species (Japanese quail, domestic chicken, and European starling; LD50's 9.4-21 mg/kg) that fed predominantly on plant material. Elevated concentrations of cyanide were found in the blood of birds that died of cyanide poisoning; however, concentrations in birds that died overlapped those in survivors. Blood was superior to liver as the tissue of choice for detecting cyanide exposure. No gross pathological changes related to dosing were observed at necropsy.

  8. Acute Sodium Ingestion Before Exercise Increases Voluntary Water Consumption Resulting In Preexercise Hyperhydration and Improvement in Exercise Performance in the Heat.

    PubMed

    Morris, David M; Huot, Joshua R; Jetton, Adam M; Collier, Scott R; Utter, Alan C

    2015-10-01

    Dehydration has been shown to hinder performance of sustained exercise in the heat. Consuming fluids before exercise can result in hyperhydration, delay the onset of dehydration during exercise and improve exercise performance. However, humans normally drink only in response to thirst, which does not result in hyperhydration. Thirst and voluntary fluid consumption have been shown to increase following oral ingestion or infusion of sodium into the bloodstream. We measured the effects of acute sodium ingestion on voluntary water consumption and retention during a 2-hr hydration period before exercise. Subjects then performed a 60-min submaximal dehydration ride (DR) followed immediately by a 200 kJ performance time trial (PTT) in a warm (30 °C) environment. Water consumption and retention during the hydration period was greater following sodium ingestion (1380 ± 580 mL consumed, 821 ± 367 ml retained) compared with placebo (815 ± 483 ml consumed, 244 ± 402 mL retained) and no treatment (782 ± 454 ml consumed, 148 ± 289 mL retained). Dehydration levels following the DR were significantly less after sodium ingestion (0.7 ± 0.6%) compared with placebo (1.3 ± 0.7%) and no treatment (1.6 ± 0.4%). Time to complete the PTT was significantly less following sodium consumption (773 ± 158 s) compared with placebo (851 ± 156 s) and no treatment (872 ± 190 s). These results suggest that voluntary hyperhydration can be induced by acute consumption of sodium and has a favorable effect on hydration status and performance during subsequent exercise in the heat.

  9. Dextran synthesized by Leuconostoc mesenteroides BD1710 in tomato juice supplemented with sucrose.

    PubMed

    Han, Jin; Hang, Feng; Guo, Benheng; Liu, Zhenmin; You, Chunpin; Wu, Zhengjun

    2014-11-04

    The characteristics of the growth of Leuconostoc mesenteroides BD1710 and the synthesis of dextran in tomato juice supplemented with 15% sucrose were assayed. L. mesenteroides BD1710 could synthesize approximately 32 g L(-1) dextran in the tomato-juice-sucrose medium when cultured at 28 °C for 48 h, which was on the same level as the dextran yield in a chemically defined medium. The viscosity of the cultured tomato-juice-sucrose medium with various dextran contents was also measured. The results of the monosaccharide composition, molecular-weight distribution, Fourier transform infrared spectra (FTIR) and nuclear magnetic resonance spectra (NMR) showed that the polysaccharide synthesized by L. mesenteroides BD1710 in the tomato-juice-sucrose medium was dextran with a peak molecular weight of 6.35 × 10(5)Da, a linear backbone composed of consecutive α-(1 → 6)-linked d-glucopyranosyl units and approximately 6% α-(1 → 3) branches. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Calciuric effects of protein and potassium bicarbonate but not of sodium chloride or phosphate can be detected acutely in adult women and men.

    PubMed

    Whiting, S J; Anderson, D J; Weeks, S J

    1997-05-01

    An acute load test was used to test the influence of dietary factors on urinary calcium excretion. In study 1, 10 fasting premenopausal women consumed test meals providing a moderate amount of protein (MP; 23 g), MP plus 23 mmol KHCO3 (MP+K), MP plus 23 mmol NaCl (MP+Na), and a high amount of protein (HP; 53 g), HP plus 70 mmol KHCO3 (HP+K), and HP plus 70 mmol NaCl (HP+Na). Protein was casein:lactalbumin (80:20), except for the treatments with added sodium chloride, to which only casein was added. In study 2, the effects of HP and HP plus 50 mmol KHCO3 (HP+K) were compared with those of MP or MP plus 7.5 mmol phosphate (MP+Pi), equaling the additional phosphate of HP, in 10 adult men. Subjects completed all treatments in random order. In study 1, the peak of calcium excretion was at 3 h for all treatments, except for HP+K, which indicated an acute hypocalciuric effect of potassium. Unexpectedly, there was no hypercalciuric effect of adding sodium chloride, nor was urine sodium increased. In study 2, calcium excretion was significantly higher with HP than with MP+Pi but not with MP at 3 h, indicating an acute hypercalciuric effect of protein alone. A hypocalciuric effect of potassium (HP+K compared with HP) but not of phosphate (MP compared with MP+Pi) was seen. An acute load test measuring changes 3 h postload was appropriate for examining the calciuric effects of protein and potassium bicarbonate, but not those of sodium chloride or phosphate in adults.

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

    PubMed

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

    2016-02-01

    Accumulating data suggest that platelets not only regulate thrombosis and haemostasis but also inflammatory processes. Platelets contain numerous potent pro-inflammatory compounds, including the chemokines CCL5 and CXCL4, although their role in acute colitis remains elusive. The aim of this study is to examine the role of platelets and platelet-derived chemokines in acute colitis. Acute colitis is induced in female Balb/c mice by administration of 5% dextran sodium sulfate (DSS) for 5 days. Animals receive a platelet-depleting, anti-CCL5, anti-CXCL4, or a control antibody prior to DSS challenge. Colonic tissue is collected for quantification of myeloperoxidase (MPO) activity, CXCL5, CXCL2, interleukin-6 (IL-6), and CCL5 levels as well as morphological analyses. Platelet depletion reduce tissue damage and clinical disease activity index in DSS-exposed animals. Platelet depletion not only reduces levels of CXCL2 and CXCL5 but also levels of CCL5 in the inflamed colon. Immunoneutralization of CCL5 but not CXCL4 reduces tissue damage, CXC chemokine expression, and neutrophil recruitment in DSS-treated animals. These findings show that platelets play a key role in acute colitis by regulating CXC chemokine generation, neutrophil infiltration, and tissue damage in the colon. Moreover, our results suggest that platelet-derived CCL5 is an important link between platelet activation and neutrophil recruitment in acute colitis. © 2015 Wiley Periodicals, Inc.

  12. The molecular mass of dextran used to modify magnetite nanoparticles affects insulin amyloid aggregation

    NASA Astrophysics Data System (ADS)

    Siposova, Katarina; Pospiskova, Kristyna; Bednarikova, Zuzana; Safarik, Ivo; Safarikova, Mirka; Kubovcikova, Martina; Kopcansky, Peter; Gazova, Zuzana

    2017-04-01

    Protein transformation from its soluble state into amyloid aggregates is associated with amyloid-related diseases. Amyloid deposits of insulin fibrils have been found in the sites of subcutaneous insulin application in patients with prolonged diabetes. Using atomic force microscopy and ThT fluorescence assay we have investigated the interference of insulin amyloid aggregation with superparamagnetic Fe3O4-based nanoparticles (SPIONs) coated with dextran (DEX); molecular mass of dextran was equal to 15-20, 40 or 70 kDa. The obtained data indicate that all three types of dextran coated nanoparticles (NP-FeDEXs) are able to inhibit insulin fibrillization and to destroy amyloid fibrils. The extent of anti-amyloid activities depends on the properties of NP-FeDEXs, mainly on the size of nanoparticles which is determined by molecular mass of dextran molecules. The most effective inhibiting activity was observed for the smallest nanoparticles coated with 15-20 kDa dextran. Contrary, the highest destroying activity was observed for the largest NP-FeDEX (70 kDa dextran).

  13. Inhibitory effects of carbohydrates on histamine release and mast cell disruption by dextran

    PubMed Central

    Beraldo, W. T.; Da Silva, W. dias; Fernandes, A. D. Lemos

    1962-01-01

    Alloxan diabetic rats failed to show the skin reaction (blue spot) evoked by dextran, whereas the effects produced by histamine and compound 48/80 were not altered. When dextran and glucose were injected simultaneously into the skin the reaction was inhibited. In vitro, mast cell alterations produced by dextran occurred simultaneously with histamine release; both processes were inhibited by glucose, other carbohydrates related to glucose, and inhibitors of anaphylaxis. These experiments suggest that dextran releases histamine by a mechanism similar to that found with 48/80 and anaphylaxis in the rat. The inhibitory effect of carbohydrates may be understood on the basis of a competitive mechanism. ImagesFig. 1Fig. 2 PMID:13967594

  14. Immunogenic properties of alpha (1----6) dextran, its protein conjugates, and conjugates of its breakdown products in mice.

    PubMed

    Mäkelä, O; Péterfy, F; Outschoorn, I G; Richter, A W; Seppälä, I

    1984-06-01

    Mice were immunized with alpha (1-6) dextran, either as such or coupled to protein carriers, and their anti-dextran response was measured by a solid-phase radioimmunoassay and the Farr assay. Like earlier investigators we found that protein-conjugated dextran was more antigenic than plain dextran. Our novel findings were that (1) a standard dose (30 micrograms of dextran per injection) coupled to strongly antigenic protein (chicken serum albumin (CSA) was three times more antigenic than dextran coupled to weakly antigenic bovine serum albumin (BSA); (2) dextrans of low molecular weight (1000-10,000 daltons) coupled to CSA induced at least ten times stronger secondary responses than did a similarly coupled macromolecular dextran (5-40 million daltons); (3) variation of the CHO/protein ratio from 0.3 to 1 had little effect on the antigenicity of the dextran. Increase of the ratio from one appeared to decrease immunogenicity when BSA was the carrier but not when CSA was the carrier.

  15. Surface functionalization of magnetic nanoparticles formed by self-associating hydrophobized oxidized dextrans

    NASA Astrophysics Data System (ADS)

    Farber, Shimon; Ickowicz, Diana E.; Melnik, Kristie; Yudovin-Farber, Ira; Recko, Daniel; Rampersaud, Arfaan; Domb, Abraham J.

    2014-06-01

    Magnetic iron oxide nanoparticles surface covered with oleic acid layer followed by a second layer of hydrophobized oxidized dextran aldehyde were prepared and tested for physico-chemical properties and ligand- and cell-specific binding. It was demonstrated that oleic acid-iron oxide nanoparticles coated with an additional layer of hydrophobized oxidized dextran were dispersible in buffer solutions and possess surface aldehyde active groups available for further binding of ligands or markers via imine or amine bond formation. Hydrophobized dextrans were synthesized by periodate oxidation and conjugation of various alkanamines to oxidized dextran by imination. Physico-chemical properties, as separation using magnetic field, magnetite concentration, and particle diameter, of the prepared magnetic samples are reported. The biotin-binding protein, neutravidin, was coupled to the particle surface by a simple reductive amination procedure. The particles were used for specific cell separation with high specificity.

  16. Radiation synthesis of biocompatible hydrogels of dextran methacrylate

    NASA Astrophysics Data System (ADS)

    Szafulera, Kamila; Wach, Radosław A.; Olejnik, Alicja K.; Rosiak, Janusz M.; Ulański, Piotr

    2018-01-01

    The aim of this work was to synthesize biocompatible dextran-based hydrogels through crosslinking initiated by ionizing radiation. A series of derivatives of dextran has been synthesized by coupling of methacrylated glycidyl to the structure of this polysaccharide, yielding dextran methacrylate (Dex-MA) of the degree of methacrylate substitution (DS) up to 1.13 as characterised by FTIR and NMR spectroscopy. Chemically crosslinked hydrogels were formed by electron-beam irradiation of Dex-MA in aqueous solution in the absence of low-molecular-weight additives such as catalysts, monomers or crosslinking agents. Crosslinking of Dex-MA in aqueous solutions of 20 g/l and above was an efficient process, the gels were formed at doses as low as 0.5 kGy (experiments conducted up to 100 kGy) and were characterised by high content of insoluble fraction (70-100%). Due to high crosslinking density the equilibrium degree of swelling of fabricated gels was controlled principally by the initial concentration of Dex-MA solution subjected to irradiation, and it was in the range of 20 to over 100 g of water absorbed by gram of gel. Cytocompatibility of hydrogels was examined using XTT assay through evaluation of the cell viability being in indirect contact with hydrogels. The results indicated that hydrogels of Dex-MA of the average DS below 1 were not cytotoxic. Altogether, our data demonstrate that irradiation of methacrylated dextran in aqueous solution is an efficient method of fabrication of biocompatible hydrogels, which applications in regeneration medicine are anticipated.

  17. Potential of novel dextran oligosaccharides as prebiotics for obesity management through in vitro experimentation.

    PubMed

    Sarbini, Shahrul R; Kolida, Sofia; Deaville, Eddie R; Gibson, Glenn R; Rastall, Robert A

    2014-10-28

    The energy-salvaging capacity of the gut microbiota from dietary ingredients has been proposed as a contributing factor for the development of obesity. This knowledge generated interest in the use of non-digestible dietary ingredients such as prebiotics to manipulate host energy homeostasis. In the present study, the in vitro response of obese human faecal microbiota to novel oligosaccharides was investigated. Dextrans of various molecular weights and degrees of branching were fermented with the faecal microbiota of healthy obese adults in pH-controlled batch cultures. Changes in bacterial populations were monitored using fluorescent in situ hybridisation and SCFA concentrations were analysed by HPLC. The rate of gas production and total volume of gas produced were also determined. In general, the novel dextrans and inulin increased the counts of bifidobacteria. Some of the dextrans were able to alter the composition of the obese human microbiota by increasing the counts of Bacteroides-Prevotella and decreasing those of Faecalibacterium prausnitzii and Ruminococcus bromii/R. flavefaciens. Considerable increases in SCFA concentrations were observed in response to all substrates. Gas production rates were similar during the fermentation of all dextrans, but significantly lower than those during the fermentation of inulin. Lower total gas production and shorter time to attain maximal gas production were observed during the fermentation of the linear 1 kDa dextran than during the fermentation of the other dextrans. The efficacy of bifidobacteria to ferment dextrans relied on the molecular weight and not on the degree of branching. In conclusion, there are no differences in the profiles between the obese and lean human faecal fermentations of dextrans.

  18. Dextrans produced by lactic acid bacteria exhibit antiviral and immunomodulatory activity against salmonid viruses.

    PubMed

    Nácher-Vázquez, Montserrat; Ballesteros, Natalia; Canales, Ángeles; Rodríguez Saint-Jean, Sylvia; Pérez-Prieto, Sara Isabel; Prieto, Alicia; Aznar, Rosa; López, Paloma

    2015-06-25

    Viral infections in the aquaculture of salmonids can lead to high mortality and substantial economic losses. Thus, there is industrial interest in new molecules active against these viruses. Here we describe the production, purification, and the physicochemical and structural characterization of high molecular weight dextrans synthesized by Lactobacillus sakei MN1 and Leuconostoc mesenteroides RTF10. The purified dextrans, and commercial dextrans with molecular weights ranging from 10 to 2000kDa, were assayed in infected BF-2 and EPC fish cell-line monolayers for antiviral activity. Only T2000 and dextrans from MN1 and RTF10 had significant antiviral activity. This was similar to results obtained against infectious pancreatic necrosis virus. However the dextran from MN1 showed ten-fold higher activity against hematopoietic necrosis virus than T2000. In vivo assays using the MN1 polymer confirmed the in vitro results and revealed immunomodulatory activity. These results together with the high levels of dextran production (2gL(-1)) by Lb. sakei MN1, indicate the compounds potential utility as an antiviral agent in aquaculture. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Dextran vesicular carriers for dual encapsulation of hydrophilic and hydrophobic molecules and delivery into cells.

    PubMed

    Pramod, P S; Takamura, Kathryn; Chaphekar, Sonali; Balasubramanian, Nagaraj; Jayakannan, M

    2012-11-12

    Dextran vesicular nanoscaffolds were developed based on polysaccharide and renewable resource alkyl tail for dual encapsulation of hydrophilic and hydrophobic molecules (or drugs) and delivery into cells. The roles of the hydrophobic segments on the molecular self-organization of dextran backbone into vesicles or nanoparticles were investigated in detail. Dextran vesicles were found to be a unique dual carrier in which water-soluble molecules (like Rhodamine-B, Rh-B) and polyaromatic anticancer drug (camptothecin, CPT) were selectively encapsulated in the hydrophilic core and hydrophobic layer, respectively. The dextran vesicles were capable of protecting the plasma-sensitive CPT lactone pharmacophore against the hydrolysis by 10× better than the CPT alone in PBS. The aliphatic ester linkage connecting the hydrophobic tail with dextran was found to be cleaved by esterase under physiological conditions for fast releasing of CPT or Rh-B. Cytotoxicity of the dextran vesicle and its drug conjugate were tested on mouse embryonic fibroblast cells (MEFs) using MTT assay. The dextran vesicular scaffold was found to be nontoxic to living cells. CPT loaded vesicles were found to be 2.5-fold more effective in killing fibroblasts compared to that of CPT alone in PBS. Confocal microscopic images confirmed that both Rh-B and CPT loaded vesicles to be taken up by fibroblasts compared to CPT alone, showing a distinctly perinuclear localization in cells. The custom designed dextran vesicular provides new research opportunities for dual loading and delivering of hydrophilic and hydrophobic drug molecules.

  20. Interactions between acidified dispersions of milk proteins and dextran or dextran sulfate.

    PubMed

    Pachekrepapol, U; Horne, D S; Lucey, J A

    2014-09-01

    Polysaccharides are often used to stabilize cultured milk products, although the nature of these interactions is not entirely clear. The objective of this study was to investigate phase behavior of milk protein dispersions with added dextran (DX; molecular weight = 2 × 10(6) Da) or dextran sulfate (DS; molecular weight = 1.4 × 10(6) Da) as examples of uncharged and charged polysaccharides, respectively. Reconstituted skim milk (5-20% milk solids, wt/wt) was acidified to pH 4.4, 4.6, 4.8, or 4.9 at approximately 0°C (to inhibit gelation) by addition of 3 N HCl. Dextran or DS was added to acidified milk samples to give concentrations of 0 to 2% (wt/wt) and 0 to 1% (wt/wt) polysaccharide, respectively. Milk samples were observed for possible phase separation after storage at 0°C for 1 and 24h. Possible gelation of these systems was determined by using dynamic oscillatory rheology. The type of interactions between caseins and DX or DS was probed by determining the total carbohydrate analysis of supernatants from phase-separated samples. At 5.0 to 7.5% milk solids, phase separation of milk samples occurred after 24h even without DX or DS addition, due to destabilization of caseins in these acidic conditions, and a stabilizing effect was observed when 0.7 or 1.0% DS was added. At higher milk solids content, phase separation was not observed without DX or DS addition. Similar results were observed at all pH levels. Gelation occurred in samples containing high milk solids (≥10%) with the addition of 1.0 to 2.0% DX or 0.4 to 1.0% DS. Based on carbohydrate analysis of supernatants, we believe that DX interacted with milk proteins through a type of depletion flocculation mechanism, whereas DS appeared to interact via electrostatic-type interactions with milk proteins. This study helps to explain how uncharged and charged stabilizers influence the texture of cultured dairy products. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All

  1. Acute oral safety study of sodium caseinate glycosylated via maillard reaction with galactose in rats.

    PubMed

    Anadón, Arturo; Martínez, Maria A; Ares, Irma; Castellano, Victor; Martínez-Larrañaga, Maria R; Corzo-Martínez, Marta; Moreno, F Javier; Villamiel, Mar

    2014-03-01

    In order to potentially use sodium caseinate (SC) glycated with galactose (Gal) in the food industry as a new functional ingredient with proved technological and biological properties, an evaluation of oral acute toxicity has been carried out. An acute safety study with SC-Gal glycoconjugates in the Wistar rat with a single oral gavage dose of 2,000 mg/kg of body weight was conducted. The SC-Gal glycoconjugates were well tolerated; no adverse effects or mortality was observed during the 2-week observation period. No abnormal signs, behavioral changes, body weight changes, or alterations in food and water consumption occurred. After this period, no changes in hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology were detected. It was concluded that SC-Gal glycoconjugates obtained via the Maillard reaction were well tolerated in rats at an acute oral dose of 2,000 mg/kg of body weight. The SC-Gal glycoconjugates have a low order of acute toxicity, and the oral 50 % lethal dose for male and female rats is in excess of 2,000 mg/kg of body weight.

  2. Have you tried spermine? A rapid and cost-effective method to eliminate dextran sodium sulfate inhibition of PCR and RT-PCR.

    PubMed

    Krych, Łukasz; Kot, Witold; Bendtsen, Katja M B; Hansen, Axel K; Vogensen, Finn K; Nielsen, Dennis S

    2018-01-01

    The Dextran Sulfate Sodium (DSS) induced colitis mouse model is commonly used to investigate human inflammatory bowel disease (IBD). Nucleic acid extracts originating from these animals are often contaminated with DSS, which is a strong inhibitor of many enzymatic based molecular biology reactions including PCR and reverse-transcription (RT). Methods for removing DSS from nucleic acids extracts exist for RNA, but no effective protocol for DNA or cDNA is currently available. However, spermine has previously been shown to be an effective agent for counteracting DSS inhibition of polynucleotide kinase, which led to the hypothesis, that spermine could be used to counteract DSS inhibition of PCR and RT. We investigated the means of adding spermine in an adequate concentration to PCR based protocols (including qPCR, two-step RT-qPCR, and amplicon sequencing library preparation) to remove DSS inhibition. Within the range up to 0.01g/L, spermine can be added to PCR/qPCR or RT prophylactically without a significant reduction of reaction efficiency. Addition of spermine at the concentration of 0.08g/L can be used to recover qualitative PCR signal inhibited by DSS in concentrations up to 0.32g/L. For optimal quantitative analysis, the concentration of spermine requires fine adjustment. Hence, we present here a simple fluorometric based method for adjusting the concentration of spermine ensuring an optimal efficiency of the reaction exposed to an unknown concentration of DSS. In conclusion, we demonstrate a cost effective and easy method to counteract DSS inhibition in PCR and two-step RT-qPCR. Fixed or fine-tuned concentrations of spermine can be administered depending on the qualitative or quantitative character of the analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. In Vitro Fermentation of Linear and α-1,2-Branched Dextrans by the Human Fecal Microbiota▿

    PubMed Central

    Sarbini, Shahrul R.; Kolida, Sofia; Naeye, Thierry; Einerhand, Alexandra; Brison, Yoann; Remaud-Simeon, Magali; Monsan, Pierre; Gibson, Glenn R.; Rastall, Robert A.

    2011-01-01

    The role of structure and molecular weight in fermentation selectivity in linear α-1,6 dextrans and dextrans with α-1,2 branching was investigated. Fermentation by gut bacteria was determined in anaerobic, pH-controlled fecal batch cultures after 36 h. Inulin (1%, wt/vol), which is a known prebiotic, was used as a control. Samples were obtained at 0, 10, 24, and 36 h of fermentation for bacterial enumeration by fluorescent in situ hybridization and short-chain fatty acid analyses. The gas production of the substrate fermentation was investigated in non-pH-controlled, fecal batch culture tubes after 36 h. Linear and branched 1-kDa dextrans produced significant increases in Bifidobacterium populations. The degree of α-1,2 branching did not influence the Bifidobacterium populations; however, α-1,2 branching increased the dietary fiber content, implying a decrease in digestibility. Other measured bacteria were unaffected by the test substrates except for the Bacteroides-Prevotella group, the growth levels of which were increased on inulin and 6- and 70-kDa dextrans, and the Faecalibacterium prausnitzii group, the growth levels of which were decreased on inulin and 1-kDa dextrans. A considerable increase in short-chain fatty acid concentration was measured following the fermentation of all dextrans and inulin. Gas production rates were similar among all dextrans tested but were significantly slower than that for inulin. The linear 1-kDa dextran produced lower total gas and shorter time to attain maximal gas production compared to those of the 70-kDa dextran (branched) and inulin. These findings indicate that dextrans induce a selective effect on the gut flora, short-chain fatty acids, and gas production depending on their length. PMID:21666027

  4. β-CD-dextran polymer for efficient sequestration of cholesterol from phospholipid bilayers: Mechanistic and safe-toxicity investigations.

    PubMed

    Stelzl, Dominik; Nielsen, Thorbjørn Terndrup; Hansen, Terkel; di Cagno, Massimiliano

    2015-12-30

    The aim of this work was to investigate the suitability of β-cyclodextrin-dextran (BCD-dextran) polymer as cholesterol sequestering agent in vitro. For this purpose, BCD-dextran-cholesterol complexation was studied by phase solubility studies as well as with a specifically designed in vitro model based on giant unilamellar vesicles (GUVs) to evaluate the ability of this polymer to sequestrate cholesterol from phospholipid bilayers. Cholesterol-sequestering ability of BCD-dextran was also investigated on different cell lines relevant for the hematopoietic system and results were correlated to cells toxicity. BCD-dextran polymer was capable of extracting significant amount of cholesterol from phospholipid bilayers and to a higher extent in comparison to available β-cyclodextrins (BCDs). The ability of BCD-dextran in sequestering cholesterol resulted also very high on cell lines relevant for the hematopoietic system. Moreover, BCD-dextran resulted less toxic on cell cultures due to higher selectivity in sequestering cholesterol in comparison to MBCD (that sequestrated also significant amounts of cholesteryl esters). In conclusion, BCD-dextran resulted an extremely efficient cholesterol-sequestering agent and BCD-dextran resulted more selective to cholesterol extraction in comparison to other BCDs (therefore of lower cytotoxicity). This phenomenon might play a key role to develop an efficient treatment for hypercholesterolemia based on cholesterol segregation. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Dextran hydrogels by crosslinking with amino acid diamines and their viscoelastic properties.

    PubMed

    O'Connor, Naphtali A; Jitianu, Mihaela; Nunez, Greisly; Picard, Quentin; Wong, Madeline; Akpatsu, David; Negrin, Adam; Gharbaran, Rajendra; Lugo, Daniel; Shaker, Sundus; Jitianu, Andrei; Redenti, Stephen

    2018-05-01

    Amine functionalized polysaccharide hydrogels such as those based on chitosan are widely examined as biomaterials. Here we set out to develop a facile procedure for developing such hydrogels by crosslinking dextran with amino acid diamines. The dextran-amino acid gels were formed by the addition of the amino acid diamines to a dextran and epichlorohydrin solution once it became homogeneous. This was demonstrated with three amino acid diamines, lysine, lysine methyl ester, and cystine dimethyl ester. Hydrogel networks with albumin entrapped were also demonstrated. These hydrogels were characterized by FTIR, SEM, rotational rheometry, swelling studies and cell biocompatibility analysis. These hydrogels showed the unexpected pH-responsive behavior of greater swelling at more basic pH, similar to that of an anionic hydrogel. This is uncharacteristic for amine functionalized gels as they typically exhibit cationic hydrogel behavior. All hydrogels showed similar biocompatibility to that of dextran crosslinked without amino acids. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. The low molecular weight Dextran 40 inhibits the adhesion of T lymphocytes to endothelial cells

    PubMed Central

    TERMEER, C C; WEISS, J M; SCHÖPF, E; VANSCHEIDT, W; SIMON, J C

    1998-01-01

    Dextrans are complex colloidal macromolecules widely used as haemorrheologic substances and anti-thrombotic agents. Here we describe a novel function of Dextran 40 by demonstrating an inhibition of T lymphocyte adhesion to endothelial cells (EC). We applied an established microassay in which constitutive and tumour necrosis factor-alpha (TNF-α)-induced binding of mouse T lymphoma cells (TK-1) to mouse endothelioma (eEND.2) cells is mediated by the interaction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on EC with their counter-receptors the LFA-1 heterodimer (CD11a/CD18) and VLA-4 on T cells. Dextran 40 in therapeutically achievable levels (2–32 mg/ml) reduced both constitutive and TNF-α-stimulated TK-1 adhesion to eEND.2. Selective preincubation of eEND.2 or TK-1 revealed that Dextran 40 acted exclusively on the T cells. To explore further the mechanisms by which Dextran 40 interfered with TK-1 adhesion, their LFA-1 and VLA-4 expression was analysed by FACS. The surface expression levels of neither receptor were affected by Dextran 40. However, confocal microscopy revealed that Dextran 40 interfered with the activation-dependent capping and clustering of LFA-1 and VLA-4 on the surface of TK-1. We conclude that Dextran 40 inhibits the capacity of TK-1 T cells to adhere to eEND.2 endothelial cells and thus may be useful for therapeutic intervention in diseases associated with enhanced T lymphocyte binding to microvascular endothelium. PMID:9844053

  7. Different protective actions of losartan and tempol on the renal inflammatory response to acute sodium overload.

    PubMed

    Rosón, María I; Della Penna, Silvana L; Cao, Gabriel; Gorzalczany, Susana; Pandolfo, Marcela; Toblli, Jorge E; Fernández, Belisario E

    2010-07-01

    The aim of this work was to study the role of local intrarenal angiotensin II (Ang II) and the oxidative stress in the up-regulation of pro-inflammatory cytokines expression observed in rats submitted to an acute sodium overload. Sprague-Dawley rats were infused for 2 h with isotonic saline solution (Control group) and with hypertonic saline solution alone (Na group), plus the AT1 receptor antagonist losartan (10 mg kg(-1) in bolus) (Na-Los group), or plus the superoxide dismutase mimetic tempol (0.5 mg min(-1) kg(-1)) (Na-Temp group). Mean arterial pressure, glomerular filtration rate, and fractional sodium excretion (FE(Na)) were measured. Ang II, NF-kappaB, hypoxia inducible factor-1 alpha (HIF-1 alpha), transforming growth factor beta1 (TGF-beta1), smooth muscle actin (alpha-SMA), endothelial nitric oxide synthase (eNOS), and RANTES renal expression was evaluated by immunohistochemistry. Ang II, NF-kappaB, and TGF-beta1 and RANTES early inflammatory markers were overexpressed in Na group, accompanied by enhanced HIF-1 alpha immunostaining, lower eNOS expression, and unmodified alpha-SMA. Losartan and tempol increased FE(Na) in sodium overload group. Although losartan reduced Ang II and NF-kappaB staining and increased eNOS expression, it did not restore HIF-1 alpha expression and did not prevent inflammation. Conversely, tempol increased eNOS and natriuresis, restored HIF-1 alpha expression, and prevented inflammation. Early inflammatory markers observed in rats with acute sodium overload is associated with the imbalance between HIF-1 alpha and eNOS expression. While both losartan and tempol increased natriuresis and eNOS expression, only tempol was effective in restoring HIF-1 alpha expression and down-regulating TGF-beta1 and RANTES expression. The protective role of tempol, but not of losartan, in the inflammatory response may be associated with its greater antioxidant effects. (c) 2010 Wiley-Liss, Inc.

  8. 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.

  9. Sodium Bicarbonate for the Prevention of Contrast Induced-Acute Kidney Injury: A Systematic Review and Meta-analysis

    PubMed Central

    Hiremath, Swapnil; Dangas, George; Mehran, Roxana; Brar, Simerjeet K.; Leon, Martin B.

    2009-01-01

    Background and objectives: Infusion of sodium bicarbonate has been suggested as a preventative strategy but reports are conflicting on its efficacy. The aim of this study was to assess the effectiveness of hydration with sodium bicarbonate for the prevention of contrast-induced acute kidney injury (CI-AKI). Design, setting, participants, & measurements: Medline, EMBASE, Cochrane library, and the Internet were searched for randomized controlled trials comparing hydration between sodium bicarbonate and chloride for the prevention of CI-AKI between 1966 and November 2008. Fourteen trials that included 2290 patients were identified. There was significant heterogeneity between studies (P heterogeneity = 0.02; I2 = 47.8%), which was largely accounted for by trial size (P = 0.016). Trials were therefore classified by size. Results: Three trials were categorized as large (n = 1145) and 12 as small (n = 1145). Among the large trials, the incidence of CI-AKI for sodium bicarbonate and sodium chloride was 10.7 and 12.5%, respectively; the relative risk (RR) [95% confidence interval (CI)] was 0.85 (0.63 to 1.16) without evidence of heterogeneity (P = 0.89, I2 = 0%). The pooled RR (95% CI) among the 12 small trials was 0.50 (0.27 to 0.93) with significant between-trial heterogeneity (P = 0.01; I2 = 56%). The small trials were more likely to be of lower methodological quality. Conclusions: A significant clinical and statistical heterogeneity was observed that was largely explained by trial size and published status. Among the large randomized trials there was no evidence of benefit for hydration with sodium bicarbonate compared with sodium chloride for the prevention of CI-AKI. The benefit of sodium bicarbonate was limited to small trials of lower methodological quality. PMID:19713291

  10. The use of chitosan-dextran gel shows anti-inflammatory, antibiofilm, and antiproliferative properties in fibroblast cell culture.

    PubMed

    Paramasivan, Sathish; Jones, Damien; Baker, Leonie; Hanton, Lyall; Robinson, Simon; Wormald, Peter J; Tan, Lorwai

    2014-01-01

    Chitosan-dextran gel has been used as an antihemostatic agent and antiadhesive agent after endoscopic sinus surgery. Because Staphylococcus aureus biofilms have been implicated in recalcitrant chronic rhinosinusitis, this study aimed to further investigate the (i) anti-inflammatory, (ii) bacterial biofilm inhibition, (iii) antiproliferative effects, and (iv) wound-healing properties of chitosan and chitosan-dextran gel. Fibroblasts were isolated from human nasal tissue and were used to determine the effects of chitosan and chitosan-dextran gel on (i) cell proliferation, (ii) wound healing, (iii) inflammation in fibroblast cultures challenged with superantigens S. aureus enterotoxin B (SEB) and toxic shock syndrome toxin (TSST), and (iv) on S. aureus biofilms. Chitosan was highly effective at reducing IL-8 expression after TSST and SEB challenge. Chitosan was also effective at reducing IL-8 expression of nonchallenged fibroblasts showing its anti-inflammatory effects on fibroblasts in a diseased state. Chitosan-dextran gel showed strong antibiofilm properties at 50% (v/v) concentration in vitro. Dextran, on its own, showed antibiofilm properties at 1.25% (w/v) concentration. Chitosan, on its own, reduced proliferation of fibroblasts to 82% of control proliferation and chitosan-dextran gel reduced proliferation of the fibroblasts to 0.04% of control proliferation. Relative to the no treatment controls, chitosan-dextran gel significantly delayed the wound-healing rate over the first 48 hours of the experiment. Chitosan-dextran gel reduced fibroblast proliferation and wound-healing time, showing a possible mechanism of reducing adhesions in the postsurgical period. Chitosan reduced IL-8 levels, showing its anti-inflammatory properties. Chitosan-dextran gel and dextran treatment showed antibiofilm properties in our model.

  11. High impact of in situ dextran coating on biocompatibility, stability and magnetic properties of iron oxide nanoparticles.

    PubMed

    Shaterabadi, Zhila; Nabiyouni, Gholamreza; Soleymani, Meysam

    2017-06-01

    Biocompatible ferrofluids based on dextran coated iron oxide nanoparticles were fabricated by conventional co-precipitation method. The experimental results show that the presence of dextran in reaction medium not only causes to the appearance of superparamagnetic behavior but also results in significant suppression in saturation magnetization of dextran coated samples. These results can be attributed to size reduction originated from the role of dextran as a surfactant. Moreover, weight ratio of dextran to magnetic nanoparticles has a remarkable influence on size and magnetic properties of nanoparticles, so that the sample prepared with a higher weight ratio of dextran to nanoparticles has the smaller size and saturation magnetization compare with the other samples. In addition, the ferrofluids containing such nanoparticles have an excellent stability at physiological pH for several months. Furthermore, the biocompatibility studies reveal that surface modification of nanoparticles by dextran dramatically decreases the cytotoxicity of bare nanoparticles and consequently improves their potential application for diagnostic and therapeutic purposes. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The Role of Dextran Coatings on the Cytotoxicity Properties of Ceria Nanoparticles Toward Bone Cancer Cells

    NASA Astrophysics Data System (ADS)

    Yazici, Hilal; Alpaslan, Ece; Webster, Thomas J.

    2015-04-01

    Cerium oxide nanoparticles have demonstrated great potential as antioxidant and radioprotective agents for nanomedicine applications especially for cancer therapy. The surface chemistry of nanoparticles is an important property that has a significant effect on their performance in biological applications including cancer diagnosis, cancer treatment, and bacterial infection. Recently, various nanosized cerium oxide particles with different types of polymer coatings have been developed to improve aqueous solubility and allow for surface functionalization for distinct applications. In this study, the role of ceria nanoparticles coated with dextran on the cytotoxicity properties of bone cancer cells was shown. Specifically, 0.1 M and 0.01 M dextran-coated, <5-nm ceria nanoparticles, were synthesized. The cytotoxicity of 0.1 M and 0.01 M dextran-coated ceria nanoparticles was evaluated against osteosarcoma cells. A change in cell viability was observed when treating osteosarcoma cells with 0.1 M dextran-coated ceria nanoparticles in the 250 -1000 μg/mL concentration range. In contrast, minimal toxicity to bone cancer cells was observed for the 0.01 M dextran coating after 3 days compared with the 0.1 M dextran coating. These results indicated that surface dextran functionalization had a positive impact on the cytotoxicity of cerium oxide nanoparticles against osteosarcoma cells.

  13. Probing Conformational Change of Bovine Serum Albumin–Dextran Conjugates under Controlled Dry Heating

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

    Xia, Shuqin; Li, Yunqi; Zhao, Qin

    2015-04-29

    The time-dependent conformational change of bovine serum album (BSA) during Maillard reaction with dextran under controlled dry heating has been studied by small-angle X-ray scattering, fluorescence spectroscopy, dynamic light scattering, and circular dichroism analysis. Through the research on the radii of gyration (R g), intrinsic fluorescence, and secondary structure, conjugates with dextran coating were found to inhibit BSA aggregation and preserve the secondary structure of native BSA against long-time heat treatment during Maillard reaction. The results suggested that the hydrophilic dextran was conjugated to the compact protein surface and enclosed it and more dextran chains were attached to BSA withmore » the increase of the heating time. The study presented here will be beneficial to the understanding of the conformational evolution of BSA molecules during the dry-heating Maillard reaction and to the control of the protein–polysaccharide conjugate structure.« less

  14. Isolation of dextran-hydrolyzing intestinal bacteria and characterization of their dextranolytic activities.

    PubMed

    Kim, Jin Kyoung; Shin, So-Yeon; Moon, Jin Seok; Li, Ling; Cho, Seung Kee; Kim, Tae-Jip; Han, Nam Soo

    2015-06-01

    The aim of this study was to isolate dextran-hydrolyzing bacteria from the human intestines and to identify their dextranolytic enzymes. For this, dextranase-producing microorganisms were screened from fecal samples by using blue dextran-containing media. Colonies producing a decolorized zone were isolated and they were grouped using RAPD-PCR. 16S rRNA gene sequencing analysis revealed the isolates were Bacteroides (B.) thetaiotaomicron, B. ovatus, B. vulgatus, B. dorei, B. xylanisolvens, B. uniformis, and Veillonella (V.) rogosae. Thin layer chromatography analysis showed that the dextranases exhibit mainly endo-type activity and produce various oligosaccharides including isomaltose and isomaltotriose. Zymogram analysis demonstrated that enzymes localized mainly in the cell membrane fraction and the molecular weight was 50-70 kDa. When cultured in a dextran-containing medium, all strains isolated in this study produced short-chain fatty acids, with butyric acid as the major compound. This is the first study to report that human intestinal B. xylanisolvens, B. dorei, and V. rogosae metabolize dextran utilizing dextranolytic enzymes. © 2015 Wiley Periodicals, Inc.

  15. Efficient fabrication of high-capacity immobilized metal ion affinity chromatographic media: The role of the dextran-grafting process and its manipulation.

    PubMed

    Zhao, Lan; Zhang, Jingfei; Huang, Yongdong; Li, Qiang; Zhang, Rongyue; Zhu, Kai; Suo, Jia; Su, Zhiguo; Zhang, Zhigang; Ma, Guanghui

    2016-03-01

    Novel high-capacity Ni(2+) immobilized metal ion affinity chromatographic media were prepared through the dextran-grafting process. Dextran was grafted to an allyl-activated agarose-based matrix followed by functionalization for the immobilized metal ion affinity chromatographic media. With elaborate regulation of the allylation degree, dextran was completely or partly grafted to agarose microspheres, namely, completely dextran-grafted agarose microspheres and partly dextran-grafted ones, respectively. Confocal laser scanning microscope results demonstrated that a good adjustment of dextran-grafting degree was achieved, and dextran was distributed uniformly in whole completely dextran-grafted microspheres, while just distributed around the outside of the partly dextran-grafted ones. Flow hydrodynamic properties were improved greatly after the dextran-grafting process, and the flow velocity increased by about 30% compared with that of a commercial chromatographic medium (Ni Sepharose FF). A significant improvement of protein binding performance was also achieved by the dextran-grafting process, and partly dextran-grafted Ni(2+) chelating medium had a maximum binding capacity for His-tagged lactate dehydrogenase about 2.5 times higher than that of Ni Sepharose FF. The results indicated that this novel chromatographic medium is promising for applications in high-efficiency and large-scale protein purification. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Dextran loading protects macrophages from lipid peroxidation and induces a Keap1/Nrf2/ARE-dependent antioxidant response.

    PubMed

    Chechushkov, Anton; Zaitseva, Natalia; Vorontsova, Elena; Kozhin, Petr; Menshchikova, Elena; Shkurupiy, Vyacheslav

    2016-12-01

    Linear dextrans are often proposed as drug delivery systems with milder adverse effects and lower effective drug concentrations. Linear dextrans are polysaccharides that can potentially be used to load macrophages with drugs to transport them to a site of inflammation. Recently, it was reported that dextrans may exert a protective effect vis-à-vis drug cytotoxicity and during wound healing. The aim of the current work was to evaluate molecular mechanisms of action of dextrans that may be relevant to the cytoprotective effects. We determined the effect of treatment with 40- or 70-kDa dextran on production of reactive oxygen species, lipid peroxidation, and lysosomal pH in the J774 macrophage cell line. In addition, induction of Keap1/Nrf2/ARE and autophagic activity were evaluated. Dextrans of both molecular weights protected the cells from oxidative stress induced by cumene hydroperoxide and from lysosomal stress induced by ammonium chloride. The effect was associated with induction of the Keap1/Nrf2/ARE signaling pathway. Furthermore, dextran stimulated autophagy in a dose-dependent manner but inhibited the autophagosome-lysosome fusion in a time-dependent manner. This study shows possible cytoprotective effects of dextran under oxidative stress, and these findings may be used for the development of novel (dextran-based) drug delivery approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Enzyme-linked immunosorbent assay for S100A9 in the stool of rats with dextran sulfate sodium-induced colitis.

    PubMed

    Sekiya, Shunsuke; Murata, Makoto; Arai, Satoshi; Murayama, Hiroshi; Kawasaki, Atushi; Ashida, Noriyuki; Okada, Kohki; Ikemoto, Masaki

    2016-12-01

    Calprotectin, a heterodimer of S100A8 and S100A9, has been reported to be a useful biomarker in inflammatory bowel disease (IBD); however, the relationship between the fecal level of S100A9 and the extent of inflammation in IBD remains unclear. Our aim was to develop a new enzyme-linked immunosorbent assay (ELISA) for rat S100A9, and to investigate whether changes in fecal S100A9 levels reflect the inflammatory conditions in the intestinal tracts of rats with dextran sulfate sodium (DSS)-induced colitis. Anti-rat S100A9 monoclonal antibodies were raised in mice and used for the development of a novel ELISA for rat S100A9. The performance of our ELISA was assessed by dilution and recovery tests, and the detection range was 3.75-240ng/mL. The dilution test showed good linearity. The recovery of fecal S100A9 was 95.1% (mean), with a range of 86.1%-108.8%. Colitis was induced in rats by oral administration of 3% DSS/drinking water (DW) for 11days (D group), while DW alone was provided to rats of the control group (C group) during the same period. The extent of inflammation was evaluated with the disease activity index (DAI), and the concentration of fecal S100A9 was determined by ELISA. Both the DAI scores and the fecal S100A9 levels were significantly higher in the D group than in the C group. Microscopic observation revealed that S100A9 was dominantly produced in many immune cells of myeloid origin in rat rectal tissues. These results indicate that the novel ELISA may be applied to clinically evaluate IBD in rats with high sensitivity. In conclusion, our ELISA is useful in toxicological and pharmacological evaluations. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Clinical effectiveness analysis of dextran 40 plus dexamethasone on the prevention of fat embolism syndrome.

    PubMed

    Liu, Xi-Ming; Huang, Jin-Cheng; Wang, Guo-Dong; Lan, Sheng-Hui; Wang, Hua-Song; Pan, Chang-Wu; Zhang, Ji-Ping; Cai, Xian-Hua

    2014-01-01

    This study aims to investigate the clinical efficacy of Dextran 40 plus dexamethasone on the prevention of fat embolism syndrome (FES) in high-risk patients with long bone shaft fractures. According to the different preventive medication, a total of 1837 cases of long bone shaft fracture patients with injury severity score (ISS) > 16 were divided into four groups: dextran plus dexamethasone group, dextran group, dexamethasone group and control group. The morbidity and mortality of FES in each group were analyzed with pairwise comparison analysis. There were totally 17 cases of FES and 1 case died. The morbidity of FES was 0.33% in dextran plus dexamethasone group and significantly lowers than that of other groups (P < 0.05). There was no significant difference among other groups (P > 0.05). Conclusion from our data is dextran 40 plus dexamethasone can effectively prevent long bone shaft fractures occurring in high-risk patients with FES.

  19. Role of β-Interferon Inducer (DEAE-Dextran) in Tumorigenesis by VEGF and NOTCH1 Inhibition along with Apoptosis Induction.

    PubMed

    Bakrania, Anita K; Variya, Bhavesh C; Patel, Snehal S

    2017-01-01

    As a novel target for breast cancer, interferon inducers have found its role as anti-angiogenic agents with diethylaminoethyl dextran (DEAE-Dextran) being a molecule used for centuries as a transfection agent. Our results herein offer an explanation for the emergence of DEAE-Dextran as an anti-tumor agent for TNBC with in-depth mechanistic approach as an anti-angiogenic molecule. DEAE-Dextran has found to possess cytotoxic activity demonstrated during the various in vitro cytotoxicity assays; moreover, as an anti-oxidant, DEAE-Dextran has shown to possess excellent reactive oxygen species scavenging activity. The interferon inducing capacity of DEAE-Dextran was determined qualitatively as well as quantitatively specifically demonstrating overexpression of β-interferon. As a measure of anti-proliferative activity, DEAE-Dextran exhibited reduced ki67, p53, and PCNA levels. Also, overexpression of CK5/6 and p63 in DEAE-Dextran treated animals indicated improvement in breast cell morphology along with an improvement in cell-cell adhesion by virtue of upregulation of β-catenin and E-cadherin. Anti-angiogenic property of DEAE-Dextran was concluded by the downregulation of CD31, VEGF, and NOTCH1 both in vivo and in vitro . Further, apoptosis due to DEAE-Dextran, initially determined by downregulation of Bcl2, was confirmed with flow cytometry. Overall, results are defensive of DEAE-Dextran as an emerging anti-tumor agent with mechanisms pertaining to β-interferon induction with probable VEGF and NOTCH1 inhibition as well as apoptosis which still needs to be studied in further depth.

  20. Role of β-Interferon Inducer (DEAE-Dextran) in Tumorigenesis by VEGF and NOTCH1 Inhibition along with Apoptosis Induction

    PubMed Central

    Bakrania, Anita K.; Variya, Bhavesh C.; Patel, Snehal S.

    2017-01-01

    As a novel target for breast cancer, interferon inducers have found its role as anti-angiogenic agents with diethylaminoethyl dextran (DEAE-Dextran) being a molecule used for centuries as a transfection agent. Our results herein offer an explanation for the emergence of DEAE-Dextran as an anti-tumor agent for TNBC with in-depth mechanistic approach as an anti-angiogenic molecule. DEAE-Dextran has found to possess cytotoxic activity demonstrated during the various in vitro cytotoxicity assays; moreover, as an anti-oxidant, DEAE-Dextran has shown to possess excellent reactive oxygen species scavenging activity. The interferon inducing capacity of DEAE-Dextran was determined qualitatively as well as quantitatively specifically demonstrating overexpression of β-interferon. As a measure of anti-proliferative activity, DEAE-Dextran exhibited reduced ki67, p53, and PCNA levels. Also, overexpression of CK5/6 and p63 in DEAE-Dextran treated animals indicated improvement in breast cell morphology along with an improvement in cell–cell adhesion by virtue of upregulation of β-catenin and E-cadherin. Anti-angiogenic property of DEAE-Dextran was concluded by the downregulation of CD31, VEGF, and NOTCH1 both in vivo and in vitro. Further, apoptosis due to DEAE-Dextran, initially determined by downregulation of Bcl2, was confirmed with flow cytometry. Overall, results are defensive of DEAE-Dextran as an emerging anti-tumor agent with mechanisms pertaining to β-interferon induction with probable VEGF and NOTCH1 inhibition as well as apoptosis which still needs to be studied in further depth. PMID:29311933

  1. Sodium bicarbonate does not prevent postoperative acute kidney injury after off-pump coronary revascularization: a double-blinded randomized controlled trial.

    PubMed

    Soh, S; Song, J W; Shim, J K; Kim, J H; Kwak, Y L

    2016-10-01

    Acute kidney injury (AKI) is a common morbidity after off-pump coronary revascularization. We investigated whether perioperative administration of sodium bicarbonate, which might reduce renal injury by alleviating oxidative stress in renal tubules, prevents postoperative AKI in off-pump coronary revascularization patients having renal risk factors. Patients (n=162) having at least one of the following AKI risk factors were enrolled: (i) age >70 yr; (ii) diabetes mellitus; (iii) chronic renal disease; (iv) congestive heart failure or left ventricular ejection fraction <35%; and (v) reoperation or emergency. Patients were evenly randomized to receive either sodium bicarbonate (0.5 mmol kg -1 for 1 h upon induction of anaesthesia followed by 0.15 mmol kg -1 h -1 for 23 h) or 0.9% saline. Acute kidney injury within 48 h after surgery was assessed using the Acute Kidney Injury Network criteria. The incidences of AKI were 21 and 26% in the bicarbonate and control groups, respectively (P=0.458). Serially measured serum creatinine concentrations and perioperative fluid balance were also comparable between the groups. The length of postoperative hospitalization and incidence of morbidity end points were similar between the groups, whereas significantly more patients in the bicarbonate group required prolonged mechanical ventilation (>24 h) relative to the control group (20 vs 6, P=0.003). Perioperative sodium bicarbonate administration did not decrease the incidence of AKI after off-pump coronary revascularization in high-risk patients and might even be associated with a need for prolonged ventilatory care. NCT01840241. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. 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

  3. Decreased Urinary Sodium-to-urinary Creatinine Ratio Identifies Sodium Depletion in Pediatric Acute Gastroenteritis.

    PubMed

    Heinz-Erian, P; Akdar, Z; Haerter, B; Waldegger, S; Giner, T; Scholl-Bürgi, S; Mueller, T

    2016-01-01

    In acute gastroenteritis (AG) fecal losses may cause depletion of sodium (NaD) which may not be recognized because of normal plasma Na (pNa) concentrations. We studied the incidence of this state of normonatremic sodium depletion (NNaD) and the suitability of the urinary Na/urinary creatinine ratio (uNa/uCr) for diagnosing NNaD. 16 AG- and 16 healthy control children aged 0.8-15.0 years. Prospective cross sectional pilot study. Measurements of Na, K and creatinine in plasma (p) and urine (u). Calculation of uNa/uCr Ratio, fractional excretion of Na (FENa) and uNa/uK ratio as the hitherto best known parameters of prerenal Na depletion, respectively. pNa concentrations were normal in 15/16 AG patients (93.8%) with only one subnormal value of 133 mmol/L, and a mean value of 137.9±2.3 mmol/L not different from the normal control group (139.4±2.2 mmol/L). Also, mean uNa concentrations and uNa/uK ratios did not differ between both groups. However, uNa/uCr ratios were below normal in 13/16 AG children (81.3%) but normal in all healthy controls with a significantly lower mean value in the AG group (12.6±8.8 vs. 31.2±8.3 mmol/mmol; p<0.0001). Similarly, 14/16 AG patients (87.5%) had a decreased FENa<0.5% with a mean FENa value significantly lower than in controls (0.36±0.28% vs. 0.95±0.26%, p<0.0001). The good agreement between FENa and uNa/uCr results was also reflected by a high correlation coefficient of r=0.9333. The majority of AG patients was found to have NNaD as determined by uNa/uCr and FENa. Calculation of uNa/uCr may be useful for diagnosing NNaD in AG. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Randomised trial of no hydration vs. sodium bicarbonate hydration in patients with chronic kidney disease undergoing acute computed tomography-pulmonary angiography.

    PubMed

    Kooiman, J; Sijpkens, Y W J; van Buren, M; Groeneveld, J H M; Ramai, S R S; van der Molen, A J; Aarts, N J M; van Rooden, C J; Cannegieter, S C; Putter, H; Rabelink, T J; Huisman, M V

    2014-10-01

    Hydration to prevent contrast-induced acute kidney injury (CI-AKI) induces a diagnostic delay when performing computed tomography-pulmonary angiography (CTPA) in patients suspected of having acute pulmonary embolism. To analyze whether withholding hydration is non-inferior to sodium bicarbonate hydration before CTPA in patients with chronic kidney disease (CKD). We performed an open-label multicenter randomized trial between 2009 and 2013. One hundred thirty-nine CKD patients were randomized, of whom 138 were included in the intention-to-treat population: 67 were randomized to withholding hydration and 71 were randomized to 1-h 250 mL 1.4% sodium bicarbonate hydration before CTPA. Primary outcome was the increase in serum creatinine 48-96 h after CTPA. Secondary outcomes were the incidence of CI-AKI (creatinine increase > 25%/> 0.5 mg dL(-1) ), recovery of renal function, and the need for dialysis within 2 months after CTPA. Withholding hydration was considered non-inferior if the mean relative creatinine increase was ≤ 15% compared with sodium bicarbonate. Mean relative creatinine increase was -0.14% (interquartile range -15.1% to 12.0%) for withholding hydration and -0.32% (interquartile range -9.7% to 10.1%) for sodium bicarbonate (mean difference 0.19%, 95% confidence interval -5.88% to 6.25%, P-value non-inferiority < 0.001). CI-AKI occurred in 11 patients (8.1%): 6 (9.2%) were randomized to withholding hydration and 5 (7.1%) to sodium bicarbonate (relative risk 1.29, 95% confidence interval 0.41-4.03). Renal function recovered in 80.0% of CI-AKI patients within each group (relative risk 1.00, 95% confidence interval 0.54-1.86). None of the CI-AKI patients developed a need for dialysis. Our results suggest that preventive hydration could be safely withheld in CKD patients undergoing CTPA for suspected acute pulmonary embolism. This will facilitate management of these patients and prevents delay in diagnosis as well as unnecessary start of

  5. Fabrication of curcumin-loaded bovine serum albumin (BSA)-dextran nanoparticles and the cellular antioxidant activity.

    PubMed

    Fan, Yuting; Yi, Jiang; Zhang, Yuzhu; Yokoyama, Wallace

    2018-01-15

    Bovine serum albumin (BSA)-dextran conjugate was prepared with glycation. Self-assembly nanoparticles were synthesized with a green, and facile approach. The effects of dry-heating time on the fabrication and characteristics of BSA-dextran conjugate nanoparticles were examined. Stable nanoparticles (<200nm) were formed after only 6h dry-heating because enough dextran was grafted onto the BSA to provide significant steric hindrance. Particle size decreased with the increase of dry-heating time and the lowest particle size (51.2nm) was obtained after 24h dry-heating. The nanoparticles were stable in a wide pH range (pH 2.0-7.0). The particle size of nanoparticles increased to 115nm after curcumin incorporation and was stable even after one-month storage. TEM results demonstrated that curcumin-loaded nanoparticles displayed a spherical structure and were homogeneously dispersed. Curcumin in BSA-dextran nanoparticle showed better stability, compared to free curcumin. In addition, BSA-dextran nanoparticles can improve the cellular antioxidant activity of curcumin in Caco-2 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Final report on the safety assessment of potassium silicate, sodium metasilicate, and sodium silicate.

    PubMed

    Elmore, Amy R

    2005-01-01

    Potassium Silicate, Sodium Metasilicate, and Sodium Silicate combine metal cations with silica to form inorganic salts used as corrosion inhibitors in cosmetics. Sodium Metasilicate also functions as a chelating agent and Sodium Silicate as a buffering and pH adjuster. Sodium Metasilicate is currently used in 168 formulations at concentrations ranging from 13% to 18%. Sodium Silicate is currently used in 24 formulations at concentrations ranging from 0.3% to 55%. Potassium Silicate and Sodium Silicate have been reported as being used in industrial cleaners and detergents. Sodium Metasilicate is a GRAS (generally regarded as safe) food ingredient. Aqueous solutions of Sodium Silicate species are a part of a chemical continuum of silicates based on an equilibrium of alkali, water, and silica. pH determines the solubility of silica and, together with concentration, determines the degree of polymerization. Sodium Silicate administered orally is readily absorbed from the alimentary canal and excreted in the urine. The toxicity of these silicates has been related to the molar ratio of SiO2/Na2O and the concentration being used. The Sodium Metasilicate acute oral LD50 ranged from 847 mg/kg in male rats to 1349.3 mg/kg in female rats and from 770 mg/kg in female mice to 820 mg/kg in male mice. Gross lesions of variable severity were found in the oral cavity, pharynx, esophagus, stomach, larynx, lungs, and kidneys of dogs receiving 0.25 g/kg or more of a commercial detergent containing Sodium Metasilicate; similar lesions were also seen in pigs administered the same detergent and dose. Male rats orally administered 464 mg/kg of a 20% solution containing either 2.0 or 2.4 to 1.0 ratio of sodium oxide showed no signs of toxicity, whereas doses of 1000 and 2150 mg/kg produced gasping, dypsnea, and acute depression. Dogs fed 2.4 g/kg/day of Sodium Silicate for 4 weeks had gross renal lesions but no impairment of renal function. Dermal irritation of Potassium Silicate, Sodium

  7. Dextran Utilization During Its Synthesis by Weissella cibaria RBA12 Can Be Overcome by Fed-Batch Fermentation in a Bioreactor.

    PubMed

    Baruah, Rwivoo; Deka, Barsha; Kashyap, Niharika; Goyal, Arun

    2018-01-01

    Weissella cibaria RBA12 produced a maximum of 9 mg/ml dextran (with 90% efficiency) using shake flask culture under the optimized concentration of medium components viz. 2% (w/v) of each sucrose, yeast extract, and K 2 HPO 4 after incubation at optimized conditions of 20 °C and 180 rpm for 24 h. The optimized medium and conditions were used for scale-up of dextran production from Weissella cibaria RBA12 in 2.5-l working volume under batch fermentation in a bioreactor that yielded a maximum of 9.3 mg/ml dextran (with 93% efficiency) at 14 h. After 14 h, dextran produced was utilized by the bacterium till 18 h in its stationary phase under sucrose depleted conditions. Dextran utilization was further studied by fed-batch fermentation using sucrose feed. Dextran on production under fed-batch fermentation in bioreactor gave 35.8 mg/ml after 32 h. In fed-batch mode, there was no decrease in dextran concentration as observed in the batch mode. This showed that the utilization of dextran by Weissella cibaria RBA12 is initiated when there is sucrose depletion and therefore the presence of sucrose can possibly overcome the dextran hydrolysis. This is the first report of utilization of dextran, post-sucrose depletion by Weissella sp. studied in bioreactor.

  8. Effects of Liposomal Compositions with Oxidized Dextrans on Functional Activity of U937 Macrophage-Like Cells In Vitro.

    PubMed

    Kozhin, P M; Chechushkov, A V; Zaitseva, N S; Lemza, A E; Men'shchikova, E B; Troitskii, A V; Shkurupy, V A

    2015-11-01

    We studied the effects of liposomal pharmaceutical compositions with oxidized dextrans on functional activity of U937 monocyte/macrophage-like cells. Liposomes in the emulsion contained oxidized dextran with a molecular weights of 40 kDa or 70 kDa or isonicotinic acid hydrazide (INAH) conjugated with oxidized dextran (40 kDa). Cell viability was evaluated by MTT test; mitochondrial transmembrane potential and production of superoxide anion and H2O2 were studied by fluorescent methods. The studied compositions exhibited no cytotoxic effect and even improved cell viability and mitochondrial respiration. Liposomes with oxidized 40 kDa dextran, including those with INAH-conjugated dextran, inhibited production of superoxide anion, but increased H2O2 generation.

  9. A Patient with MSUD: Acute Management with Sodium Phenylacetate/Sodium Benzoate and Sodium Phenylbutyrate.

    PubMed

    Köse, Melis; Canda, Ebru; Kagnici, Mehtap; Uçar, Sema Kalkan; Çoker, Mahmut

    2017-01-01

    In treatment of metabolic imbalances caused by maple syrup urine disease (MSUD), peritoneal dialysis, and hemofiltration, pharmacological treatments for elimination of toxic metabolites can be used in addition to basic dietary modifications. Therapy with sodium phenylacetate/benzoate or sodium phenylbutyrate (NaPB) in urea-cycle disorder cases has been associated with a reduction in branched-chain amino acid (BCAA) concentrations when the patients are on adequate dietary protein intake. Moreover, NaPB in treatment of MSUD patients is also associated with reduction of BCAA levels in a limited number of cases. However, there are not enough studies in the literature about application and efficacy of this treatment. Our case report sets an example of an alternative treatment's efficacy when extracorporeal procedures are not available due to technical difficulties during attack period of the disease.

  10. Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine.

    PubMed

    Weisbord, Steven D; Gallagher, Martin; Jneid, Hani; Garcia, Santiago; Cass, Alan; Thwin, Soe-Soe; Conner, Todd A; Chertow, Glenn M; Bhatt, Deepak L; Shunk, Kendrick; Parikh, Chirag R; McFalls, Edward O; Brophy, Mary; Ferguson, Ryan; Wu, Hongsheng; Androsenko, Maria; Myles, John; Kaufman, James; Palevsky, Paul M

    2018-02-15

    Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy. Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point. The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury. Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research

  11. Rye bran as fermentation matrix boosts in situ dextran production by Weissella confusa compared to wheat bran.

    PubMed

    Kajala, Ilkka; Mäkelä, Jari; Coda, Rossana; Shukla, Shraddha; Shi, Qiao; Maina, Ndegwa Henry; Juvonen, Riikka; Ekholm, Päivi; Goyal, Arun; Tenkanen, Maija; Katina, Kati

    2016-04-01

    The consumption of fiber-rich foods such as cereal bran is highly recommended due to its beneficial health effects. Pre-fermentation of bran with lactic acid bacteria can be used to improve the otherwise impaired flavor and textural qualities of bran-rich products. These positive effects are attributed to enzymatic modification of bran components and the production of functional metabolites like organic acids and exopolysaccharides such as dextrans. The aim of this study was to investigate dextran production in wheat and rye bran by fermentation with two Weissella confusa strains. Bran raw materials were analyzed for their chemical compositions and mineral content. Microbial growth and acidification kinetics were determined from the fermentations. Both strains produced more dextran in rye bran in which the fermentation-induced acidification was slower and the acidification lag phase longer than in wheat bran. Higher dextran production in rye bran is expected to be due to the longer period of optimal pH for dextran synthesis during fermentation. The starch content of wheat bran was higher, which may promote isomaltooligosaccharide formation at the expense of dextran production. W. confusa Cab3 produced slightly higher amounts of dextran than W. confusa VTT E-90392 in all raw materials. Fermentation with W. confusa Cab3 also resulted in lower residual fructose content which has technological relevance. The results indicate that wheat and particularly rye bran are promising matrices for producing technologically significant amounts of dextran, which facilitates the use of nutritionally valuable raw bran in food applications.

  12. Intravenous parecoxib sodium as an analgesic alternative to morphine in acute trauma pain in the emergency department.

    PubMed

    Baharuddin, Kamarul Aryffin; Rahman, Nik Hisamuddin Na; Wahab, Shaik Farid Abdull; Halim, Nurkhairulnizam A; Ahmad, Rashidi

    2014-01-03

    Parecoxib sodium is the first parenteral COX-2 inhibitor used for pain management licensed for postoperative pain. However, no study has assessed the usage of parecoxib for acute traumatic pain in the emergency department (ED). The objective of this study was to investigate a potential alternative analgesic agent in the ED by determining the mean reduction of pain score between acute traumatic pain patients who were administered with intravenous (IV) parecoxib sodium versus IV morphine sulfate. The onset of perceptible analgesic effect and side effects were also evaluated. A randomized, double-blinded study comparing IV parecoxib 40 mg versus IV morphine at 0.10 mg/kg was conducted in adult patients presented with acute traumatic pain with numeric rating scale (NRS) of 6 or more within 6 hours of injury. Patients were randomized using a computer-generated randomization plan. Drug preparation and dispensing were performed by a pharmacist. Periodic assessment of blood pressure, pulse rate, oxygen saturation, and NRS were taken at 0, 5, 15, and 30 minute intervals after the administration of the study drug. The primary outcome was the reduction of NRS. Side effect and drug evaluation was conducted within 30 minutes of drug administration. There was no statistically significant difference in the reduction of mean NRS between patients in the IV parecoxib group or IV morphine group (P = 0.095). The mean NRS for patients treated with IV morphine were 7.1 at 0 minutes, 4.5 at 5 minutes, 3.1 at 15 minutes, and 2.0 at 30 minutes. Whereas mean NRS for patients who received IV parecoxib were 7.8 at 0 minutes, 5.7 at 5 minutes, 4.7 at 15 minutes, and 3.9 at 30 minutes. The onset of perceptible analgesic effects could be seen as early as 5 minutes. Dizziness was experienced in 42.9% of patients who received IV morphine compared to none in the parecoxib group. There was non-significant trend toward superiority of IV morphine over IV parecoxib. Looking at its effectiveness

  13. Intravenous parecoxib sodium as an analgesic alternative to morphine in acute trauma pain in the emergency department

    PubMed Central

    2014-01-01

    Background Parecoxib sodium is the first parenteral COX-2 inhibitor used for pain management licensed for postoperative pain. However, no study has assessed the usage of parecoxib for acute traumatic pain in the emergency department (ED). The objective of this study was to investigate a potential alternative analgesic agent in the ED by determining the mean reduction of pain score between acute traumatic pain patients who were administered with intravenous (IV) parecoxib sodium versus IV morphine sulfate. The onset of perceptible analgesic effect and side effects were also evaluated. Methods A randomized, double-blinded study comparing IV parecoxib 40 mg versus IV morphine at 0.10 mg/kg was conducted in adult patients presented with acute traumatic pain with numeric rating scale (NRS) of 6 or more within 6 hours of injury. Patients were randomized using a computer-generated randomization plan. Drug preparation and dispensing were performed by a pharmacist. Periodic assessment of blood pressure, pulse rate, oxygen saturation, and NRS were taken at 0, 5, 15, and 30 minute intervals after the administration of the study drug. The primary outcome was the reduction of NRS. Side effect and drug evaluation was conducted within 30 minutes of drug administration. Results There was no statistically significant difference in the reduction of mean NRS between patients in the IV parecoxib group or IV morphine group (P = 0.095). The mean NRS for patients treated with IV morphine were 7.1 at 0 minutes, 4.5 at 5 minutes, 3.1 at 15 minutes, and 2.0 at 30 minutes. Whereas mean NRS for patients who received IV parecoxib were 7.8 at 0 minutes, 5.7 at 5 minutes, 4.7 at 15 minutes, and 3.9 at 30 minutes. The onset of perceptible analgesic effects could be seen as early as 5 minutes. Dizziness was experienced in 42.9% of patients who received IV morphine compared to none in the parecoxib group. Conclusions There was non-significant trend toward superiority of IV morphine over IV

  14. Dextran as a fast resorbable and mechanically stiff coating for flexible neural probes

    NASA Astrophysics Data System (ADS)

    Kil, D.; Brancato, L.; Puers, R.

    2017-11-01

    In this paper we report on the use of dextran as a temporary, fast dissolving stiff coating for flexible neural probes. Although polymer-based neural implants offer several advantages, compared to their rigid silicon counterparts, they pose significant challenges during implantation. Due to their extreme flexibility, they have the tendency to buckle under the axial load applied during insertion. The structural stiffness of the implants can be temporarily increased by applying a bioresorbable dextran coating which eases the penetration of neural tissue. For this application three types of dextran with different molecular weights are analysed. The dissolution rate of the coatings is reported as well as the increased bending stiffness resulting from the dextran coating of Parylene C neural probes. Based on these findings the dissolution rate can be linked to parameters such as molecular weight, coating thickness and the surface area exposed to the dissolution medium. The mechanical characterization yields information on how the structural stiffness of neural probes can be tuned by varying the dextran’s molecular weight and coating thickness.

  15. Water soluble cationic dextran derivatives containing poly(amidoamine) dendrons for efficient gene delivery.

    PubMed

    Mai, Kaijin; Zhang, Shanshan; Liang, Bing; Gao, Cong; Du, Wenjun; Zhang, Li-Ming

    2015-06-05

    To develop new dextran derivatives for efficient gene delivery, the conjugation of poly(amidoamine) dendrons onto biocompatible dextran was carried out by a Cu(I)-catalyzed azide-alkyne cycloaddition, as confirmed by FTIR and (1)H NMR analyses. For resultant dextran conjugates with various generations of poly(amidoamine) dendrons, their buffering capacity and in vitro cytotoxicity were evaluated by acid-base titration and MTT tests, respectively. In particular, their physicochemical characteristics for the complexation with plasmid DNA were investigated by the combined analyses from agarose gel electrophoresis, zeta potential, particle size, transmission electron microscopy and fluorescence emission spectra. Moreover, their complexes with plasmid DNA were studied with respect to their transfection efficiency in human embryonic kidney (HEK293) cell lines. In the case of a higher generation of poly(amidoamine) dendrons, such a dextran conjugate was found to have much lower cytotoxicity and better gene delivery capability when compared to branched polyethylenimine (bPEI, 25kDa), a commonly used gene vector. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Challenges in analysis of high-molar mass dextrans: comparison of HPSEC, AsFlFFF and DOSY NMR spectroscopy.

    PubMed

    Maina, Ndegwa Henry; Pitkänen, Leena; Heikkinen, Sami; Tuomainen, Päivi; Virkki, Liisa; Tenkanen, Maija

    2014-01-01

    Dilute solutions of various dextran standards, a high-molar mass (HMM) commercial dextran from Leuconostoc spp., and HMM dextrans isolated from Weissella confusa and Leuconostoc citreum were analyzed with high-performance size-exclusion chromatography (HPSEC), asymmetric flow field-flow fractionation (AsFlFFF), and diffusion-ordered NMR spectroscopy (DOSY). HPSEC analyses were performed in aqueous and dimethyl sulfoxide (DMSO) solutions, while only aqueous solutions were utilized in AsFlFFF and DOSY. The study showed that all methods were applicable to dextran analysis, but differences between the aqueous and DMSO-based solutions were obtained for HMM samples. These differences were attributed to the presence of aggregates in aqueous solution that were less prevalent in DMSO. The study showed that DOSY provides an estimate of the size of HMM dextrans, though calibration standards may be required for each experimental set-up. To our knowledge, this is the first study utilizing these three methods in analyzing HMM dextrans. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Derivatization of Dextran for Multiply Charged Ion Formation and Electrospray Ionization Time-of-Flight Mass Spectrometric Analysis

    NASA Astrophysics Data System (ADS)

    Tapia, Jesus B.; Hibbard, Hailey A. J.; Reynolds, Melissa M.

    2017-10-01

    We present the use of a simple, one-pot derivatization to allow the polysaccharide dextran to carry multiple positive charges, shifting its molecular weight distribution to a lower m/ z range. We performed this derivatization because molecular weight measurements of polysaccharides by mass spectrometry are challenging because of their lack of readily ionizable groups. The absence of ionizable groups limits proton abstraction and suppresses proton adduction during the ionization process, producing mass spectra with predominantly singly charged metal adduct ions, thereby limiting the detection of large polysaccharides. To address this challenge, we derivatized dextran T1 (approximately 1 kDa) by attaching ethylenediamine, giving dextran readily ionizable, terminal amine functional groups. The attached ethylenediamine groups facilitated proton adduction during the ionization process in positive ion mode. Using the low molecular weight dextran T1, we tracked the number of ethylenediamine attachments by measuring the mass shift from underivatized to derivatized dextran T1. Using electrospray ionization time-of-flight mass spectrometry, we observed derivatized dextran chains ranging from two to nine glucose residues with between one and four attachments/charges. Our success in shifting derivatized dextran T1 toward the low m/ z range suggests potential for this derivatization as a viable route for analysis of high molecular weight polysaccharides using electrospray ionization time-of-flight mass spectrometry. [Figure not available: see fulltext.

  18. Intra-articular clearance of labeled dextrans from naive and arthritic rat knee joints.

    PubMed

    Mwangi, Timothy K; Berke, Ian M; Nieves, Eduardo H; Bell, Richard D; Adams, Samuel B; Setton, Lori A

    2018-05-26

    Determine the effects of arthritis on the trans-synovial clearance of small and large model compounds following local delivery to the knee joint in a rat model. Intra-articular delivery was studied in rat knee joints in an osteoarthritis model of joint instability (medial collateral ligament and meniscus transection model or MMT). Fluorescently-labeled 10 kDa or 500 kDa dextran was injected in the arthritic or unoperated control (naive) joints 3 weeks after surgical destabilization, and the temporal clearance pattern was evaluated via in vivo regional fluorescence imaging, dextran concentrations in plasma and draining lymph nodes, and by quantification of fluorescence in histological synovium sections. Together these data were used to evaluate the effect of osteoarthritis and solute size on the rate of drug clearance from the joint. Clearance of 10 kDa dextran from the joint space quantified using in vivo fluorescence imaging of the knee joint region was not significantly different between naive and MMT joints. In contrast, clearance of 500 kDa dextran was significantly reduced for MMT joints when compared to naive joints by fluorescence in vivo imaging. Drug accumulation in lymph nodes and plasma were lower for the 500 kDa dextran as compared to 10 kDa dextran, and lymph node levels were further reduced with the presence of osteoarthritis. Furthermore, synovium was significantly thicker in MMT joints than in naive joints and image analysis of joint tissue sections revealed different trans-synovial distributions of 10 and 500 kDa dextran. Large macromolecules were retained in the arthritic joint longer than in the healthy joint, while smaller molecules were cleared similarly in healthy and arthritic joints. In vivo fluorescence imaging, plasma and lymph node concentrations, and spatial distributions of drug fluorescence identified differences in higher molecular weight clearance between naive and arthritic disease states. Findings may relate to a

  19. Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study.

    PubMed

    Kakkar, Ashish Kumar; Rehan, H S; Unni, K E S; Gupta, Neeraj Kumar; Chopra, Deepti; Kataria, Dinesh

    2009-04-01

    This study compared the efficacy and safety of oxcarbazepine and divalproex sodium in acute mania patients. In this 12 week, randomized, double-blind pilot study, 60 patients diagnosed with acute mania (DSM-IV) and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexibly dosed oxcarbazepine (1,000-2,400 mg/day) or divalproex (750-2,000 mg/day). The mean decrease in the YMRS score from baseline was used as the main outcome measure of response to treatment. A priori protocol-defined threshold scores were or=15 for relapse. Number of patients showing adequate response and the time taken to achieve improvement was compared. Adverse events were systematically recorded throughout the study. Over 12 weeks, mean improvement in YMRS scores was comparable for both the groups including the mean total scores as well as percentage fall from baseline. There were no significant differences between treatments in the rates of symptomatic mania remission (90% in divalproex and 80% in oxcarbazepine group) and subsequent relapse. Median time taken to symptomatic remission was 56 days in divalproex group while it was 70 days in the oxcarbazepine group (p=0.123). A significantly greater number of patients in divalproex group experienced one or more adverse drug events as compared to patients in the oxcarbazepine group (66.7% versus 30%, p<0.01). Oxcarbazepine demonstrated comparable efficacy to divalproex sodium in the management of acute mania. Also the overall adverse event profile was found to be superior for oxcarbazepine.

  20. A Patient with MSUD: Acute Management with Sodium Phenylacetate/Sodium Benzoate and Sodium Phenylbutyrate

    PubMed Central

    Canda, Ebru; Kagnici, Mehtap; Uçar, Sema Kalkan; Çoker, Mahmut

    2017-01-01

    In treatment of metabolic imbalances caused by maple syrup urine disease (MSUD), peritoneal dialysis, and hemofiltration, pharmacological treatments for elimination of toxic metabolites can be used in addition to basic dietary modifications. Therapy with sodium phenylacetate/benzoate or sodium phenylbutyrate (NaPB) in urea-cycle disorder cases has been associated with a reduction in branched-chain amino acid (BCAA) concentrations when the patients are on adequate dietary protein intake. Moreover, NaPB in treatment of MSUD patients is also associated with reduction of BCAA levels in a limited number of cases. However, there are not enough studies in the literature about application and efficacy of this treatment. Our case report sets an example of an alternative treatment's efficacy when extracorporeal procedures are not available due to technical difficulties during attack period of the disease. PMID:28589054

  1. New biodegradable dextran-based hydrogels for protein delivery: Synthesis and characterization.

    PubMed

    Pacelli, Settimio; Paolicelli, Patrizia; Casadei, Maria Antonietta

    2015-08-01

    A new derivative of dextran grafted with polyethylene glycol methacrylate through a carbonate bond (DEX-PEG-MA) has been synthesized and characterized. The photo-crosslinking reaction of DEX-PEG-MA allowed the obtainment of biodegradable networks tested for their mechanical and release properties. The new hydrogels were compared with those made of dextran methacrylate (DEX-MA), often employed as drug delivery systems of small molecules. The inclusion of PEG as a spacer created additional interactions among the polymeric chains improving the extreme fragility and lack of hardness typical of gels made of DEX-MA. Moreover, the different behavior in terms of swelling and degradability of the networks was able to affect the release of a model macromolecule over time, making DEX-PEG-MA matrices suitable candidates for the delivery of high molecular weight peptides. Interestingly, the combination of the two dextran derivatives showed intermediate ability to modulate the release of high molecular weight macromolecules. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Overexpression of alpha(1)-acid glycoprotein in transgenic mice leads to sensitisation to acute colitis.

    PubMed

    Hochepied, T; Wullaert, A; Berger, F G; Baumann, H; Brouckaert, P; Steidler, L; Libert, C

    2002-09-01

    alpha(1)-Acid glycoprotein (alpha(1)-AGP) is an acute phase protein in most mammalian species whose concentration rises 2-5-fold during an acute phase reaction. Its serum concentration has often been used as a marker of disease, including inflammatory bowel disease (IBD). High alpha(1)-AGP levels were found to have a prognostic value for an increased risk of relapse in IBD. To investigate a possible role for increased serum levels of alpha(1)-AGP in the development of IBD. Dextran sodium sulphate (DSS) 2% was added to the drinking water of transgenic mice, overexpressing the rat alpha(1)-AGP gene, to induce acute colitis, thus mimicking the conditions of relapse. Clinical parameters, inflammatory parameters, and histological analyses on colon sections were performed. Homozygous alpha(1)-AGP-transgenic mice started losing weight and showed rectal bleeding significantly earlier than heterozygous transgenic or wild-type mice. Survival time of homozygous transgenic mice was significantly shorter compared with heterozygous and wild-type mice. The higher susceptibility of homozygous alpha(1)-AGP-transgenic mice to DSS induced acute colitis was also reflected in higher local myeloperoxidase levels, higher inflammation scores of the colon, and higher systemic levels of interleukin 6 and serum amyloid P component. Local inflammatory parameters were also significantly different in heterozygous transgenic mice compared with wild-type mice, indicating a local dosage effect. In homozygous transgenic mice, significantly higher amounts of bacteria were found in organs but IgA levels were only slightly lower than those of control mice. Sufficiently high serum levels of alpha(1)-AGP result in a more aggressive development of acute colitis.

  3. Synthesis and film formation of furfuryl- and maleimido carbonic acid derivatives of dextran.

    PubMed

    Elschner, Thomas; Obst, Franziska; Stana-Kleinschek, Karin; Kargl, Rupert; Heinze, Thomas

    2017-04-01

    Carbonic acid derivatives of dextran possessing furfuryl- and maleimido moieties were synthesized and processed into thin films by spin coating. First, products with different degrees of substitution (DS) of up to 3.0 and substitution patterns were obtained and characterized by NMR- and FTIR spectroscopy, as well as elemental analysis. Thin films possessing maleimide groups were obtained by spin coating of maleimido dextran (furan-protected) and dextran furfuryl carbamate that was converted with bismaleimide. The removal of the protecting group (furan) on the thin film was monitored by QCM-D and compared with gravimetric analysis of the bulk material. Film morphology and wettability were determined by means of AFM and contact angle measurements. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Qing-dai powder promotes recovery of colitis by inhibiting inflammatory responses of colonic macrophages in dextran sulfate sodium-treated mice.

    PubMed

    Xiao, Hai-Tao; Peng, Jiao; Hu, Dong-Dong; Lin, Cheng-Yuan; Du, Bin; Tsang, Siu-Wai; Lin, Ze-Si; Zhang, Xiao-Jun; Lueng, Feng-Ping; Han, Quan-Bin; Bian, Zhao-Xiang

    2015-01-01

    Qing-dai powder (QDP), comprising Indigo naturalis (Qing-dai) and dried alum (Ku-fan), was used in Chinese medicine to treat the conditions associated with mucosal hemorrhage, such as ulcerative colitis (UC). This study aims to investigate the effects and potential mechanism of QDP on dextran sulfate sodium (DSS)-induced acute colitis in mice and to examine the regulatory effects of QDP on macrophages. Seven- to eight-week-old male C57BL/6 mice were challenged with 2.0 % DSS in drinking water for 5 days and then the colitic mice were arbitrarily allocated into five groups (n = 10 for each group). QDP (0.77, 1.54 and 3.08 g/kg) and sulfasalazine (SASP) (0.20 g/kg) were orally administered for 7 days. The disease activity index was determined by scores of body weight loss, diarrhea and rectal bleeding; histological signs of damage was analyzed by H&E staining; myeloperoxidase activity was measured by colorimetric method, levels of proinflammatory cytokines were determined by ELISA; changes in macrophages in the colon were analyzed by immunohistochemistry (IHC) and flow cytometry. Lipopolysaccharide (LPS)-induced RAW264.7 cells were treated with or without QDP, then the production of TNF-α and IL-6 were measured by ELISA; and protein molecules such as COX-2, iNOS, IкB-α were determined by Western blot. Oral administration of QDP at dosages of 1.54 and 3.08 g/kg significantly reduced disease activity index on day 12 (P < 0.001 for 1.54 g/kg and P < 0.0008 for 3.08 g/kg), colon shortening (P = 0.012 for 1.54 g/kg, P = 0.001 for 3.08 g/kg), histological damage (P < 0.001 for 1.54 g/kg, P < 0.001 for 3.08 g/kg) and colonic myeloperoxidase activity (P = 0.002 for 1.54 g/kg, P < 0.001 for 3.08 g/kg) of DSS-treated mice. Moreover, QDP treatment (1.54 and 3.08 g/kg) significantly decreased DSS-induced infiltration of macrophages, and production of TNF-α (P = 0.005 for 1.54 g/kg, P = 0.002 for 3.08 g/kg), IL-1β (P = 0.008 for 1.54

  5. Dextran-Catechin: An anticancer chemically-modified natural compound targeting copper that attenuates neuroblastoma growth

    PubMed Central

    Vittorio, Orazio; Brandl, Miriam; Cirillo, Giuseppe; Kimpton, Kathleen; Hinde, Elizabeth; Gaus, Katharina; Yee, Eugene; Kumar, Naresh; Duong, Hien; Fleming, Claudia; Haber, Michelle; Norris, Murray; Boyer, Cyrille; Kavallaris, Maria

    2016-01-01

    Neuroblastoma is frequently diagnosed at advanced stage disease and treatment includes high dose chemotherapy and surgery. Despite the use of aggressive therapy survival rates are poor and children that survive their disease experience long term side effects from their treatment, highlighting the need for effective and less toxic therapies. Catechin is a natural polyphenol with anti-cancer properties and limited side effects, however its mechanism of action is unknown. Here we report that Dextran-Catechin, a conjugated form of catechin that increases serum stability, is preferentially and markedly active against neuroblastoma cells having high levels of intracellular copper, without affecting non-malignant cells. Copper transporter 1 (CTR1) is the main transporter of copper in mammalian cells and it is upregulated in neuroblastoma. Functional studies showed that depletion of CTR1 expression reduced intracellular copper levels and led to a decrease in neuroblastoma cell sensitivity to Dextran-Catechin, implicating copper in the activity of this compound. Mechanistically, Dextran-Catechin was found to react with copper, inducing oxidative stress and decreasing glutathione levels, an intracellular antioxidant and regulator of copper homeostasis. In vivo, Dextran-Catechin significantly attenuated tumour growth in human xenograft and syngeneic models of neuroblastoma. Thus, Dextran-Catechin targets copper, inhibits tumour growth, and may be valuable in the treatment of aggressive neuroblastoma and other cancers dependent on copper for their growth. PMID:27374085

  6. Phospatidylserine or ganglioside--which of anionic lipids determines the effect of cationic dextran on lipid membrane?

    PubMed

    Hąc-Wydro, Katarzyna; Wydro, Paweł; Cetnar, Andrzej; Włodarczyk, Grzegorz

    2015-02-01

    In this work the influence of cationic polymer, namely diethylaminoethyl DEAE-dextran on model lipid membranes was investigated. This polymer is of a wide application as a biomaterial and a drug carrier and its cytotoxicity toward various cancer cells was also confirmed. It was suggested that anticancer effect of cationic dextran is connected with the binding of the polymer to the negatively charged sialic acid residues overexpressed in cancer membrane. This fact encouraged us to perform the studies aimed at verifying whether the effect of cationic DEAE-dextran on membrane is determined only by the presence of the negatively charged lipid in the system or the kind of anionic lipid is also important. To reach this goal systematic investigations on the effect of dextran on various one-component lipid monolayers and multicomponent hepatoma cell model membranes differing in the level and the kind of anionic lipids (phosphatidylserine, sialic acid-containing ganglioside GM3 or their mixture) were done. As evidenced the results the effect of DEAE-dextran on the model system is determined by anionic lipid-polymer electrostatic interactions. However, the magnitude of the effect of cationic polymer is strongly dependent on the kind of anionic lipid in the model system. Namely, the packing and ordering of the mixtures containing ganglioside GM3 were more affected by DEAE-dextran than phosphatidylserine-containing monolayers. Although the experiments were done on model systems and therefore further studies are highly needed, the collected data may indicate that ganglioside may be important in the differentiation of the effect of cationic dextran on membranes. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. 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.

  8. Characterization of the swelling-induced alkalinization of endocytotic vesicles in fluorescein isothiocyanate-dextran-loaded rat hepatocytes.

    PubMed Central

    Schreiber, R; Häussinger, D

    1995-01-01

    Short-term cultivated rat hepatocytes were allowed to endocytose fluorescein isothiocyanate (FITC)-coupled dextran and the apparent vesicular pH (pHves) was measured by single-cell fluorescence. After 2 h of exposure to FITC-dextran, the apparent pH in the vesicular compartments accessible to endocytosed FITC-dextran was 6.01 +/- 0.05 (n = 39) in normo-osmotic media. Hypo-osmotic exposure increased, whereas hyper-osmotic exposure decreased apparent pHves. by 0.18 +/- 0.02 (n = 26) and 0.12 +/- 0.01 (n = 23) respectively. Incubation of the cells with unlabelled dextran for 2h before a 2-h FITC-dextran exposure had no effect on apparent pHves and its osmosensitivity. When, however, hepatocytes were exposed to unlabelled dextran for 5 h after a 2 h exposure to FITC-dextran, in order to allow transport of endocytosed FITC-dextran to late endocytotic/lysosomal compartments, apparent pHves. decreased to 5.38 +/- 0.04 (n = 12) and the apparent pH in the vesicular compartment containing the dye was no longer sensitive to aniso-osmotic exposure. These findings indicate that the osomosensitivity of pHves. is apparently restricted to early endocytotic compartments. Aniso-osmotic regulation of apparent pHves. in freshly FITC-loaded hepatocytes was not accompanied by aniso-osmolarity-induced changes of the cytosolic free calcium concentration, and neither vasopressin nor extracellular ATP, which provoked a marked Ca2+ signal, affected apparent pHves. Dibutyryl-cyclic AMP (cAMP) or vanadate (0.5 mmol/l) were without effect on apparent pHves. and its osmosensitivity. However, pertussis toxin-treatment or genistein (but not daidzein) or the erbstatin analogue methyl 2,5-dihydroxycinnamate fully abolished the osmo-sensitivity of apparent pHves., but did not affect apparent pHves. It is concluded that regulation of pHves. by cell volume occurs in early endocytotic compartments, but probably not in lysosomes, and is mediated by a G-protein and tyrosine kinase-dependent, but Ca2+- and

  9. Characteristics of DEAE-dextran-MMA graft copolymer as a nonviral gene carrier.

    PubMed

    Onishi, Yasuhiko; Eshita, Yuki; Murashita, Aya; Mizuno, Masaaki; Yoshida, Jun

    2007-09-01

    A stable and soapless latex of diethylaminoethyl-dextran-methyl methacrylate (DEAE-dextran-MMA) graft copolymer (DDMC) has been developed for nonviral gene delivery vectors that are possible to autoclave. DDMC relatively easily formed a polyion complex between DNA and DDMC by the hydrophobic force of graft poly(MMA) depending on its large positive entropy change (DeltaS). DDMC has been confirmed as having a high protection facility for DNase by DNase degradation test.Transfection activity was determined using the beta-galactosidase assay, and a higher value of 16 times or more was confirmed for the DDMC samples in comparison with one of the starting DEAE-dextran hydrochloride samples. The resulting DDMC, having an amphiphilic domain so as to form a polymer micelle, should become a stable latex with a hydrophilic-hydrophobic microseparated domain. The complex of DDMC and plasmid DNA may be formed on the spherical structure of the amphiphilic microseparated domain of DDMC and have a good affinity to the cell membrane. The infrared absorption spectrum shift to a high-energy direction at around 3450 cm(-1), because of the complexes between DNA and DDMC, may cause the formation of more compact structures, not only by a coulomb force between the phosphoric acid of DNA and the DEAE group of DEAE-dextran copolymer but also by a force from the multi-intermolecule hydrogen bond in the backbone polymer DEAE-dextran and a hydrophobic force from the graft poly(MMA) in DDMC. It is thus concluded that DNA condensation may possibly have a high transfection efficiency via DDMC. The high efficiency of this graft copolymer, which is sterilized by an autoclave, may thus make it a valuable tool for safe gene delivery.

  10. Quantitative monitoring of activity-dependent bulk endocytosis of synaptic vesicle membrane by fluorescent dextran imaging

    PubMed Central

    Clayton, Emma Louise; Cousin, Michael Alan

    2012-01-01

    Activity-dependent bulk endocytosis (ADBE) is the dominant synaptic vesicle (SV) retrieval mode in central nerve terminals during periods of intense neuronal activity. Despite this fact there are very few real time assays that report the activity of this critical SV retrieval mode. In this paper we report a simple and quantitative assay of ADBE using uptake of large flourescent dextrans as fluid phase markers. We show that almost all dextran uptake occurs in nerve terminals, using co-localisation with the fluorescent probe FM1-43. We also demonstrate that accumulated dextran cannot be unloaded by neuronal stimulation, indicating its specific loading into bulk endosomes and not SVs. Quantification of dextran uptake was achieved by using thresholding analysis to count the number of loaded nerve terminals, since monitoring the average fluorescence intensity of these nerve terminals did not accurately report the extent of ADBE. Using this analysis we showed that dextran uptake occurs very soon after stimulation and that it does not persist when stimulation terminates. Thus we have devised a simple and quantitative method to monitor ADBE in living neurones, which will be ideal for real time screening of small molecule inhibitors of this key SV retrieval mode. PMID:19766140

  11. Sumatriptan/Naproxen Sodium: A Review in Migraine.

    PubMed

    Syed, Yahiya Y

    2016-01-01

    Sumatriptan/naproxen sodium (Treximet®) is a fixed-dose combination of a serotonin 5-HT1B/1D receptor agonist (sumatriptan) and an NSAID (naproxen sodium), approved in the USA for the acute treatment of migraine with or without aura in adolescents and adults. In a randomized, phase 3 trial in adolescents, significantly more sumatriptan/naproxen sodium than placebo recipients were pain-free at 2 h. Similarly, in a pair of randomized phase 3 trials in adults, significantly more sumatriptan/naproxen sodium than placebo recipients had relief from migraine symptoms at 2 h, and the combination was more effective than individual components in terms of sustained (2-24 h) pain-free response rate. Sumatriptan/naproxen sodium was generally well tolerated, with ≤11 % of adolescents and ≤22 % of adults reporting treatment-related adverse events in the key clinical trials. The most common adverse reactions were nasopharyngitis, hot flushes and muscle tightness in adolescents, and dizziness, pain or pressure sensations, nausea, somnolence, dry mouth, dyspepsia and paraesthesia in adults. Based on current data, sumatriptan/naproxen sodium is a useful option for the acute treatment of migraine in adolescents and adults. The fixed-dose combination may reduce pill burden and improve adherence in some patients.

  12. Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial.

    PubMed

    Nalos, Marek; Leverve, Xavier; Huang, Stephen; Weisbrodt, Leonie; Parkin, Ray; Seppelt, Ian; Ting, Iris; Mclean, Anthony

    2014-03-25

    Acute heart failure (AHF) is characterized by inadequate cardiac output (CO), congestive symptoms, poor peripheral perfusion and end-organ dysfunction. Treatment often includes a combination of diuretics, oxygen, positive pressure ventilation, inotropes and vasodilators or vasopressors. Lactate is a marker of illness severity but is also an important metabolic substrate for the myocardium at rest and during stress. We tested the effects of half-molar sodium lactate infusion on cardiac performance in AHF. We conducted a prospective, randomised, controlled, open-label, pilot clinical trial in 40 patients fulfilling two of the following three criteria for AHF: (1) left ventricular ejection fraction <40%, (2) acute pulmonary oedema or respiratory failure of predominantly cardiac origin requiring mechanical ventilation and (3) currently receiving vasopressor and/or inotropic support. Patients in the intervention group received a 3 ml/kg bolus of half-molar sodium lactate over the course of 15 minutes followed by 1 ml/kg/h continuous infusion for 24 hours. The control group received only a 3 ml/kg bolus of Hartmann's solution without continuous infusion. The primary outcome was CO assessed by transthoracic echocardiography 24 hours after randomisation. Secondary outcomes included a measure of right ventricular systolic function (tricuspid annular plane systolic excursion (TAPSE)), acid-base balance, electrolyte and organ function parameters, along with length of stay and mortality. The infusion of half-molar sodium lactate increased (mean ± SD) CO from 4.05 ± 1.37 L/min to 5.49 ± 1.9 L/min (P < 0.01) and TAPSE from 14.7 ± 5.5 mm to 18.3 ± 7 mm (P = 0.02). Plasma sodium and pH increased (136 ± 4 to 146 ± 6 and 7.40 ± 0.06 to 7.53 ± 0.03, respectively; both P < 0.01), but potassium, chloride and phosphate levels decreased. There were no significant differences in the need for vasoactive therapy, respiratory support

  13. [Glutamate dehydrogenase activity in the pancreatic tissue in acute experimental pancreatitis and under the action of sodium thiosulphate].

    PubMed

    Simavorian, P S; Saakian, I L; Gevorkian, D A

    1991-04-01

    It has been established that the development of acute pancreatitis is accompanied by the reduced activity of glutamate dehydrogenase in the mitochondrial fraction of pancreas, pronounced in the focus of tissue necrosis and less expressed in the reactive inflammation focus. Besides this in the pancreas redistribution of enzyme, activity in the subcellular organelles takes place and enzyme activity emerges in the cytosol and further--in the blood and peritoneum liquid. Sodium thiosulfate has a marked correlation effect.

  14. Sentinel lymph node mapping in melanoma with technetium-99m dextran.

    PubMed

    Neubauer, S; Mena, I; Iglesis, R; Schwartz, R; Acevedo, J C; Leon, A; Gomez, L

    2001-06-01

    The aim of this work is to evaluate the capability of Tc99m B Dextran as a lymphoscintigraphic agent in the detection of the sentinel node in skin lesions. Forty-one patients with melanomas (39) and Merkel cell tumors (2) had perilesional intradermal injection of Tc99m-Dextran 2 hours before surgery. Serial gamma camera images and a handheld gamma probe were used to direct sentinel node biopsy. In 39/41 patients, lymph channels and 52 sentinel nodes (one to three sentinel nodes/patient) could be visualized. In one patient, with a dorsal melanoma, no lymph channels or lymph nodes could be demonstrated on the images and only minimal radioactivity was found in the regional nodes with the probe. Another patient with a facial lesion failed to demonstrate lymph channels or nodes. No adverse reactions were observed. Tc99m-Dextran provided good definition of lymph channels and sentinel node localization, without the risks related to the use of potentially hazardous labeled materials of biological origin.

  15. Structural analysis and biomedical applications of dextran produced by a new isolate Pediococcus pentosaceus screened from biodiversity hot spot Assam.

    PubMed

    Patel, Seema; Kasoju, Naresh; Bora, Utpal; Goyal, Arun

    2010-09-01

    Dextran produced by a natural isolate of Pediococcus pentosaceus, screened from Assam, in the Northeastern region of India, was estimated, purified, structure characterised and functionality analysed. The dextran concentration in the cell free supernatant of the isolate P. pentosaceus was 10.2mg/ml. FT-IR analysis revealed the hydroxyl and carboxyl functional groups present in the dextran. (1)H NMR and (13)C NMR spectral data revealed that the dextran has a linear backbone of alpha-(1-->6) linked D-glucose residues. The decrease in viscosity of dextran solution with the increase in shear rate, threw light on its typical non-Newtonian pseudoplastic behaviour. The cytotoxicity tests on human cervical cancer (HeLa) cell line was studied which showed the dextran is non-toxic and biocompatible, rendering it safe for drug delivery, tissue engineering and various other biomedical applications. (c) 2010 Elsevier Ltd. All rights reserved.

  16. Dietary ω-6/ω-3 Polyunsaturated Fatty Acid Ratios Affect the Homeostasis of Th/Treg Cells in Mice With Dextran Sulfate Sodium-Induced Colitis.

    PubMed

    Huang, Cyoung-Huei; Hou, Yu-Chen; Pai, Man-Hui; Yeh, Chiu-Li; Yeh, Sung-Ling

    2017-05-01

    This study evaluated the effect of different dietary ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratios on modulating helper T (Th) and regulatory T (Treg) lymphocytes in mice with dextran sulfate sodium (DSS)-induced colitis. There were 3 control and 3 colitis groups. Mice were fed for 24 days with diets with soybean oil (S), a mixture of soybean oil and low fish oil content (LF), or high fish oil content (HF). The ratio of ω-6/ω-3 PUFA in the LF diet was 4:1, and that in the HF diet was 2:1. The control groups drank distilled water while colitis groups were provided 2% DSS in drinking water during days 15-19. All mice drank distilled water from days 20-24 for recovery and were sacrificed on day 25. Colitis resulted in higher blood Th1, Th2, and Th17 and lower Treg percentages. Also, plasma haptoglobin and proinflammatory chemokines were elevated in colon lavage fluid. Colitic groups with fish oil had lower inflammatory mediators in the plasma and colon lavage fluid. Furthermore, the percentages of blood Th1, Th2, and Th17 cells were lower, whereas Treg cell percentages were higher than those in the soybean oil group. The colitis group with an ω-6/ω-3 PUFA ratio of 2:1 had more pronounced effects than the group with a ratio of 4:1. Diets with an ω-6/ω-3 PUFA ratio of 2:1 or 4:1 regulate the Th/Treg balance and attenuate inflammatory mediator production in colitis. Compared with the ω-6/ω-3 PUFA ratio of 4:1, the ratio of 2:1 was more effective in reducing inflammatory reactions in DSS-induced colitis.

  17. Controlled release of β-carotene in β-lactoglobulin-dextran-conjugated nanoparticles' in vitro digestion and transport with Caco-2 monolayers.

    PubMed

    Yi, Jiang; Lam, Tina I; Yokoyama, Wallace; Cheng, Luisa W; Zhong, Fang

    2014-09-03

    Undesirable aggregation of nanoparticles stabilized by proteins may occur at the protein's isoelectric point when the particle has zero net charge. Stability against aggregation of nanoparticles may be improved by reacting free amino groups with reducing sugars by the Maillard reaction. β-Lactoglobulin (BLG)-dextran conjugates were characterized by SDS-PAGE and CD. Nanoparticles (60-70 nm diameter) of β-carotene (BC) encapsulated by BLG or BLG-dextran were prepared by the homogenization-evaporation method. Both BLG and BLG-dextran nanoparticles appeared to be spherically shaped and uniformly dispersed by TEM. The stability and release of BC from the nanoparticles under simulated gastrointestinal conditions were evaluated. Dextran conjugation prevented the flocculation or aggregation of BLG-dextran particles at pH ∼4-5 compared to very large sized aggregates of BLG nanoparticles. The released contents of BC from BLG and BLG-dextran nanoparticles under acidic gastric conditions were 6.2 ± 0.9 and 5.4 ± 0.3%, respectively. The release of BC from BLG-dextran nanoparticles by trypsin digestion was 51.8 ± 4.3% of total encapsulated BC, and that from BLG nanoparticles was 60.9 ± 2.9%. Neither BLG-BC nanoparticles nor the Maillard-reacted BLG-dextran conjugates were cytotoxic to Caco-2 cells, even at 10 mg/mL. The apparent permeability coefficient (Papp) of Caco-2 cells to BC was improved by nanoencapsulation, compared to free BC suspension. The results indicate that BC-encapsulated β-lactoglobulin-dextran-conjugated nanoparticles are more stable to aggregation under gastric pH conditions with good release and permeability properties.

  18. Preparation and characterization of dextran nanobubbles for oxygen delivery.

    PubMed

    Cavalli, R; Bisazza, A; Giustetto, P; Civra, A; Lembo, D; Trotta, G; Guiot, C; Trotta, M

    2009-11-03

    Dextran nanobubbles were prepared with a dextran shell and a perfluoropentan core in which oxygen was stored. To increase the stability polyvinylpirrolidone was also added to the formulation as stabilizing agent. Rhodamine B was used as fluorescent marker to obtain fluorescent nanobubbles. The nanobubble formulations showed sizes of about 500nm, a negative surface charge and a good capacity of loading oxygen, no hemolytic activity or toxic effect on cell lines. The fluorescent labelled nanobubbles could be internalized in Vero cells. Oxygen-filled nanobubbles were able to release oxygen in different hypoxic solutions at different time after their preparation in in vitro experiments. The oxygen release kinetics could be enhanced after nanobubble insonation with ultrasound at 2.5MHz. The oxygen-filled nanobubble formulations might be proposed for therapeutic applications in various diseases.

  19. Enteral supplement enriched with glutamine, fiber, and oligosaccharide attenuates experimental colitis in mice.

    PubMed

    Joo, Erina; Yamane, Shunsuke; Hamasaki, Akihiro; Harada, Norio; Matsunaga, Tetsuro; Muraoka, Atsushi; Suzuki, Kazuyo; Nasteska, Daniela; Fukushima, Toru; Hayashi, Tatsuya; Tsuji, Hidemi; Shide, Kenichiro; Tsuda, Kinsuke; Inagaki, Nobuya

    2013-03-01

    Ulcerative colitis is a chronic recurrent disease characterized by acute inflammation of the colonic mucosa. In Japan, a dietary supplementation product enriched with glutamine, dietary fiber, and oligosaccharide (GFO) is widely applied for enteral nutrition support. These three components have been suggested to improve intestinal health. In this study, we investigated whether GFO has suppressive effects on mucosal damage in ulcerative colitis in an experimental mouse model. C57BL/6 mice received 2.5% dextran sulfate sodium in drinking water for 5 d to induce colitis. Then, they were given 0.25 mL of GFO or a 20% glucose solution twice daily for 10 d. Another set of mice receiving unaltered drinking water was used as the normal control group. The body weight loss and disease activity index were significantly lower in the GFO-treated mice compared with the glucose-treated mice (P < 0.05). The decrease in colon length induced by dextran sulfate sodium was significantly alleviated in GFO-treated mice compared with glucose-treated mice (P < 0.01). In addition, the histologic findings showed that intestinal inflammation was significantly attenuated in mice treated with GFO. Furthermore, treatment with GFO significantly inhibited the dextran sulfate sodium-induced increase in the mRNA expression of interleukin-1β. These results suggest that GFO has potential therapeutic value as an adjunct therapy for ulcerative colitis. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Acute toxicity of multi-walled carbon nanotubes, sodium pentachlorophenate, and their complex on earthworm Eisenia fetida.

    PubMed

    Zhang, Liujun; Hu, Changwei; Wang, Weili; Ji, Funian; Cui, Yibin; Li, Mei

    2014-05-01

    Laboratory experiments were undertaken to relate biomarker responses to the toxicities of multi-walled carbon nanotubes (MWCNTs) and sodium pentachlorophenate (PCP-Na), both individually and combined. The acute toxicities of MWCNTs and PCP-Na on earthworm Eisenia fetida were studied through different exposure methods (filter paper contact test, immersion contact test, and artificial soil contact test). Enzyme activity and malondialdehyde (MDA) content in the earthworm E. fetida exposed to MWCNTs and PCP-Na in filter paper contact test, both individually and under combined exposure, were determined. After exposure, PCP-Na induced observable acute toxicity while the MWCNTs induced slight toxicity. Interestingly the earthworms exposed to the mixture of MWCNTs and PCP-Na demonstrated different expression of enzymatic biomarkers from those exposed to MWCNTs or PCP-Na alone. Our results indicated that the toxicity of PCP-Na on E. fetida may be alleviated by the appearance of MWCNTs for all exposure methods except for immersion contact test. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Beneficial Effect of Beraprost Sodium Plus Aspirin in the Treatment of Acute Ischemic Stroke.

    PubMed

    Chen, Siqia; Xie, Sisi; He, Wenzhen; Wei, Duncan; Li, Shunxian; Chen, Wenjie

    2017-09-12

    BACKGROUND To investigate the combination of beraprost sodium (BPS) and aspirin in the treatment of acute ischemic stroke (AIS). MATERIAL AND METHODS 308 patients with acute cerebral infarction were randomly divided into two groups: experimental group (n=154), treated with BPS (40 μg, tid) and aspirin (100 mg, qd); control group (n=154), treated with 100 mg of aspirin, qd). The antiplatelet therapy remained unchangeable until six months after hospital discharge. RESULTS Initially, no significant differences were found between the two groups. After six months, the relapse-free survival rate was similar between the treatment group (98.1%) and the control group (97.4%). One patient died from AIS in the control group. However, glomerular filtration rate was significantly higher; neurological function and functional ability of patients were better in patients treated with BPS plus aspirin (experimental group) than that in aspirin alone group. No significant difference was found in the function of the coagulation system, suggesting that BPS plus aspirin treatment did not increase the risk of bleeding. Serious adverse events did not occur in both groups. Facial flushing (one case) and mild gastrointestinal reaction (one case) were found in the treatment group without influencing treatment. CONCLUSIONS In our trial involving patients with acute cerebral infarction, BPS plus aspirin was not found to be superior to aspirin in reducing the recurrence of cerebral infarction or death. However, BPS plus aspirin treatment could improve renal function and neurological function without increasing the risk of bleeding.

  2. The role of slow and persistent TTX-resistant sodium currents in acute tumor necrosis factor-α-mediated increase in nociceptors excitability

    PubMed Central

    Gudes, Sagi; Barkai, Omer; Caspi, Yaki; Katz, Ben; Lev, Shaya

    2014-01-01

    Tetrodotoxin-resistant (TTX-r) sodium channels are key players in determining the input-output properties of peripheral nociceptive neurons. Changes in gating kinetics or in expression levels of these channels by proinflammatory mediators are likely to cause the hyperexcitability of nociceptive neurons and pain hypersensitivity observed during inflammation. Proinflammatory mediator, tumor necrosis factor-α (TNF-α), is secreted during inflammation and is associated with the early onset, as well as long-lasting, inflammation-mediated increase in excitability of peripheral nociceptive neurons. Here we studied the underlying mechanisms of the rapid component of TNF-α-mediated nociceptive hyperexcitability and acute pain hypersensitivity. We showed that TNF-α leads to rapid onset, cyclooxygenase-independent pain hypersensitivity in adult rats. Furthermore, TNF-α rapidly and substantially increases nociceptive excitability in vitro, by decreasing action potential threshold, increasing neuronal gain and decreasing accommodation. We extended on previous studies entailing p38 MAPK-dependent increase in TTX-r sodium currents by showing that TNF-α via p38 MAPK leads to increased availability of TTX-r sodium channels by partial relief of voltage dependence of their slow inactivation, thereby contributing to increase in neuronal gain. Moreover, we showed that TNF-α also in a p38 MAPK-dependent manner increases persistent TTX-r current by shifting the voltage dependence of activation to a hyperpolarized direction, thus producing an increase in inward current at functionally critical subthreshold voltages. Our results suggest that rapid modulation of the gating of TTX-r sodium channels plays a major role in the mediated nociceptive hyperexcitability of TNF-α during acute inflammation and may lead to development of effective treatments for inflammatory pain, without modulating the inflammation-induced healing processes. PMID:25355965

  3. VERSATILE, HIGH-RESOLUTION ANTEROGRADE LABELING OF VAGAL EFFERENT PROJECTIONS WITH DEXTRAN AMINES

    PubMed Central

    Walter, Gary C.; Phillips, Robert J.; Baronowsky, Elizabeth A.; Powley, Terry L.

    2009-01-01

    None of the anterograde tracers used to label and investigate vagal preganglionic neurons projecting to the viscera has proved optimal for routine and extensive labeling of autonomic terminal fields. To identify an alternative tracer protocol, the present experiment evaluated whether dextran conjugates, which have produced superior results in the CNS, might yield widespread and effective labeling of long, fine-caliber vagal efferents in the peripheral nervous system. The dextran conjugates that were evaluated proved reliable and versatile for labeling the motor neuron pool in its entirety, for single- and multiple-labeling protocols, for both conventional and confocal fluorescence microscopy, and for permanent labeling protocols for brightfield microscopy of the projections to the gastrointestinal (GI) tract. Using a standard ABC kit followed by visualization with DAB as the chromagen, Golgi-like labeling of the vagal efferent terminal fields in the GI wall was achieved with the biotinylated dextrans. The definition of individual terminal varicosities was so sharp and detailed that it was routinely practical to examine the relationship of putative vagal efferent contacts (by the criteria of high magnification light microscopy) with the dendritic and somatic architecture of counterstained neurons in the myenteric plexus. Overall, dextran conjugates provide high-definition labeling of an extensive vagal motor pool in the GI tract, and offer considerable versatility when multiple-staining protocols are needed to elucidate the complexities of the innervation of the gut. PMID:19056424

  4. Functional analysis of truncated and site-directed mutagenesis dextransucrases to produce different type dextrans.

    PubMed

    Wang, Chao; Zhang, Hong-Bin; Li, Meng-Qi; Hu, Xue-Qin; Li, Yao

    2017-07-01

    Dextrans with distinct molecular size and structure are increasingly being used in the food and pharmaceutical industries. Dextran is produced by dextransucrase (DSR, EC2.4.5.1), which is produced by Leuconostoc mesenteroides. DSR belongs to glycosyl hydrolase family (GH70) and synthesizes branched α-glucan (dextran) with both 5% α(1-3) and 95% α(1-6) glycosidic linkages. The DSR gene dex-YG (Genebank, Accession No. DQ345760) was cloned from the wild strain Leuconostoc mesenteroides 0326. This study generated a series of C-terminally truncated variants of dextransucrase and substituting the amino-acid residues in the active site of DSR. With shorter length of DSR, its polysaccharide-synthesizing capability was impaired heavily, whereas oligosaccharide (acting as prebiotics)-synthesizing capability increased significantly, efficiently producing special sizes of dextran. All truncated mutant enzymes were active. Results demonstrated that the catalytic domain dextransucrase was likely in 800 aa or less. Based on the three-dimensional structure model of dextransucrase built through homology modeling methods, the DSR and its mutants with the acceptor substrate of maltose and donor substrate of sucrose were studied by molecular-docking method. Substituting these amino-acid residues significantly affected enzyme activities. Compared with the wild-type dextran, mutant enzymes catalyzed the synthesis of a-glucan with 1-9% α(1-3) and 90-98% α(1-6) branching linkages. Some mutants introduced a small amount of α(1-4) linkages and α(1-2) linkages. This strategy can be effectively used for the rational protein design of dextransucrase. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Structural analysis and characterization of dextran produced by wild and mutant strains of Leuconostoc mesenteroides.

    PubMed

    Siddiqui, Nadir Naveed; Aman, Afsheen; Silipo, Alba; Qader, Shah Ali Ul; Molinaro, Antonio

    2014-01-01

    An exopolysaccharide known as dextran was produced by Leuconostoc mesenteroides KIBGE-IB22 (wild) and L. mesenteroides KIBGE-IB22M20 (mutant). The structure was characterized using FTIR, (1)H NMR, (13)C NMR and 2D NMR spectroscopic techniques, whereas surface morphology was analyzed using SEM. A clear difference in the spectral chemical shift patterns was observed in both samples. All the spectral data indicated that the exopolysaccharide produced by KIBGE-IB22 is a mixture of two biopolymers. One was dextran in α-(1 → 6) configuration with a small proportion of α-(1 → 3) branching and the other was levan containing β-(2 → 6) fructan fructofuranosyl linkages. However, remarkably the mutant only produced dextran without any concomitant production of levan. Study suggested that the property of KIBGE-IB22M20, regarding improved production of high molecular weight dextran in a shorter period of fermentation time without any contamination of other exopolysaccharide, could be employed to make the downstream process more feasible and cost effective on large scale. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Novel dextran derivatives with unconventional structure formed in an efficient one-pot reaction.

    PubMed

    Hotzel, Konrad; Heinze, Thomas

    2016-11-03

    An efficient one-pot synthesis of new dextran derivatives is described. The functional groups of β-alanine, i.e., the carboxyl- and amine group, are converted independently in one-step by iminium chloride to form products with a single substituent. The dextran N-[(dimethylamino)methylene]-β-alanine ester is formed selectively. The structure of the resulting polymers is unambiguously determined by means of NMR- and FTIR-spectroscopy and elemental analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. In vivo cleavage rate of a dextran-bound magnetic resonance imaging contrast agent: preparation and intravascular pharmacokinetic characteristics in the rabbit.

    PubMed

    Hals, Petter Arnt; Sontum, Per Christian; Holtz, Eckart; Klaveness, Jo; Rongved, Pål

    2013-02-01

    Earlier described dextran-based contrast agents for magnetic resonance imaging (MRI) comprising the gadolinium chelate diethylenetriamine pentaacetic acid (GdDTPA, 1) have shown significantly shorter in vivo contrast duration in rat than what would be expected from the initial average molecular weight (Mw) of the dextran fraction (71.4 kD). To investigate this further, four dextran fractions with given initial average molecular weight (Mw) of 10.4, 41.0, 71.4 and 580 kD were used as starting material to prepare products 2-5 where one of the carboxylic acid functionalities in GdDTPA was used as a direct covalent ester linker to hydroxyl groups in dextrans. A fifth derivative (6) was an amide-ester bound β-alanine-DTPAGd conjugate with dextran having Mw 71.4 kD. The reference compound GdDTPA (1) and gadoliniumlabelled dextran derivatives 2-6 were injected intravenously in rabbits. Pharmacokinetic parameters showed that when GdDTPA is ester-bound directly to dextran hydroxyls, the cleavage rates of 2-5 were only moderately dependent on the molecular weights of the dextrans, having blood pool half-lives comparable to the low-molecular reference compound (t 1/2,β 0.3 - 0.5 hrs.). Presence of a β-alanine spacer in 6 prolonged the plasma half-life t 1/2,β to 6.9 hours, rendering a blood residence time suitable for blood pool slow release of GdDTPA. Biological cleavage regenerates the clinically acceptable carrier dextran and the β-alanine derivative of GdDTPA, pointing at a clinically acceptable product class for blood-pool contrast in MRI.

  8. Optimization of dextran production by Leuconostoc mesenteroides NRRL B-512 using cheap and local sources of carbohydrate and nitrogen.

    PubMed

    Behravan, Javad; Bazzaz, B Seddigheh Fazly; Salimi, Zohreh

    2003-12-01

    Using pure components for the fermentation medium in dextran production imposes high costs on the industry. In the present study, the economic production of dextran using local and cheap sources of carbohydrate and nitrogen was investigated. Different concentrations of molasses and wheat-bran extract, after filtration, steam sterilization and pH adjustment, were inoculated with a fresh suspension of Leuconostoc mesenteroides. Cultures were incubated, and then diluted with an equal volume of ethanol. The bacteria were pelleted, and an aliquot of the supernatant was diluted with ethanol and dextran was precipitated. The supernatant was removed and the precipitate was dissolved in a minimal volume of water. Activated charcoal was added and the solution was boiled. The solution was filtered and protein impurities removed by 2-methylbutan-2-ol/chloroform extraction. Dextran was again precipitated with cold ethanol as described above, and the precipitate was dried in a desiccator. Optimum conditions and composition of culture media for dextran production using sugar-beet molasses and wheat bran were determined. The best results were obtained when 20% (w/v) molasses and 15% (w/v) wheat bran were used. The optimal initial pH for dextran production was 7.5.

  9. Acute and repeated dose inhalation toxicity of para-nitrophenol sodium salt in rats.

    PubMed

    Smith, L W; Hall, G T; Kennedy, G L

    1988-01-01

    Para-Nitrophenol Sodium Salt (PNSP) has relatively low acute inhalation toxicity; the 4-hr Approximate Lethal Concentration in rats is greater than 4.7 mg/l. One subacute study was conducted at 0, 0.34 and 2.47 mg PNSP/l for ten 6-hr exposures. Darker urine, proteinuria and elevated creatinine and SGOT were seen after exposure and were still evident after 14 days recovery. Methemoglobinemia also was seen and was reversible at 0.34 mg/l after 14 days. In addition, exposure to 2.47 mg/l caused elevated erythrocytes, hemoglobin and hematocrit. A second subacute study at 0.03 and 0.13 mg PNSP/l showed reversible methemoglobinemia only at 0.13 mg/l. The repeated dose no-observable effect level was 0.03 mg/l. No compound-related pathologic changes were noted in any of the studies.

  10. 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.

  11. Synthesis and Characterization of Water-soluble Conjugates of Cabazitaxel Hemiesters-Dextran.

    PubMed

    Parhizkar, Elahehnaz; Ahmadi, Fatemeh; Daneshamouz, Saeid; Mohammadi-Samani, Soliman; Sakhteman, Amirhossein; Parhizkar, Golnaz

    2017-11-24

    Cabazitaxel (CTX) is a second- generation taxane derivative, a class of potent anticancer drugs with very low water solubility. CTX is used in patients with resistant prostate cancer unresponsive to the first generation taxane, docetaxel. Currently marketed formulations of CTX contain high concentrations of surfactant and ethanol, which cause severe hypersensitivity reactions in patients. In order to increase its solubility, two hemiester analogs; CTX-succinate and CTX-glutarate were synthesized and characterized. To improve the solubility of hemiesters even more, dextran as a biocompatible polymer was also conjugated to hemiester analogs. MTT assay was performed on MCF-7 cell line to evaluate the cytotoxicity effect of hemiesters and conjugates. Based on the results, hemiester analogs increased water solubility of the drug up to about 3 and 8 fold. Conjugation to dextran enhanced the CTX solubility to more than 1500 fold. These conjugates released the conjugated CTX in less than 24 hours in a pH dependent manner and showed proper hemocompatibility characteristics. The hemiesters had approximately similar cytotoxicity in comparison with CTX and the dextran conjugates showed higher cytotoxicity effect on MCF-7 cell line. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Insights from diversified anti-angiogenic models: Role of β-interferon inducer DEAE-Dextran.

    PubMed

    Bakrania, Anita K; Variya, Bhavesh C; Patel, Snehal S

    2018-04-17

    Angiogenesis, the physiological process involving growth of new blood vessels from preexisting vessels, is essential for organ growth and repair. However, the imbalance in angiogenesis contributes to copious pathologies including cancer. Preceding the development of anti-angiogenic or proangiogenic agents, its evaluation is equally imperative; hence, precise and adequate models required. Valid mammalian models are expensive, time-consuming and not easy to set up, instigating legal and ethical aspects making it necessary to establish models with satisfactory activity and limited drawbacks. We investigated the activity of DEAE-Dextran on diversified models viz. in vitro cell migration assay, ex vivo aortic ring assay, in vitro chick yolk sac membrane assay and in vivo matrigel plug xenograft model corroborating its anti-angiogenic potential and establishing the best means of evaluation. Assorted models were reproducible and correlative to one another. DEAE-Dextran exhibited excellent anti-angiogenic effect in cell migration assay over a duration of 24 h compared to the vehicle control fibroblast cell line and aortic ring possessed an alleviated rate of sprouting when treated with DEAE-Dextran with contrast to vehicle control aorta. Similarly, decreased vascular density was observed in DEAE-Dextran treated chick embryos implicating potency of the β-interferon inducer. Augmenting to these results, the matrigel plugs also mitigated vascular net as well as reduced levels of angiogenic marker CD31. Substantially, DEAE-Dextran leads to anti-tumor activity through anti-angiogenic action and a combination of in vitro and in vivo model is vital for the judgement of anti-angiogenic potential since an in vitro model exempts mammalian-culture considerations. Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  13. Synthesis and chromatographic characterization of dextran-coated zirconia high-performance liquid chromatographic stationary phases.

    PubMed

    Dunlap, C J; Carr, P W

    1996-10-11

    Porous zirconia particles made by the oil emulsion (OE) method and the polymerization-induced colloid aggregation (PICA) method have been coated with a small, carboxymethylated (approximately 5%) dextran polymer and crosslinked in place. The parameters of the coating process (dextran concentration, adsorption time and crosslinker concentration) have all been examined and an optimum value for each determined. The coated and uncoated materials were characterized by nitrogen sorptometry and size-exclusion chromatography (SEC) using solutes (polystyrenes and dextrans) of well-defined molecular masses. Nitrogen sorptometry results show that the PICA material has a much lower pore volume and smaller pore diameter than do the OE materials. Despite this, the elution volumes of the SEC probes change very little upon polymer coating the PICA material while the OE material shows a very large change upon coating.

  14. Dietary Sodium Restriction Decreases Insulin Secretion Without Affecting Insulin Sensitivity in Humans

    PubMed Central

    Byrne, Loretta M.; Yu, Chang; Wang, Thomas J.; Brown, Nancy J.

    2014-01-01

    Context: Interruption of the renin-angiotensin-aldosterone system prevents incident diabetes in high-risk individuals, although the mechanism remains unclear. Objective: To test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system or exogenous aldosterone impairs insulin secretion in humans. Design: We conducted a randomized, blinded crossover study of aldosterone vs vehicle and compared the effects of a low-sodium versus a high-sodium diet. Setting: Academic clinical research center. Participants: Healthy, nondiabetic, normotensive volunteers. Interventions: Infusion of exogenous aldosterone (0.7 μg/kg/h for 12.5 h) or vehicle during low or high sodium intake. Low sodium (20 mmol/d; n = 12) vs high sodium (160 mmol/d; n = 17) intake for 5–7 days. Main Outcome Measures: Change in acute insulin secretory response assessed during hyperglycemic clamps while in sodium balance during a low-sodium vs high-sodium diet during aldosterone vs vehicle. Results: A low-sodium diet increased endogenous aldosterone and plasma renin activity, and acute glucose-stimulated insulin (−16.0 ± 5.6%; P = .007) and C-peptide responses (−21.8 ± 8.4%; P = .014) were decreased, whereas the insulin sensitivity index was unchanged (−1.0 ± 10.7%; P = .98). Aldosterone infusion did not affect the acute insulin response (+1.8 ± 4.8%; P = .72) or insulin sensitivity index (+2.0 ± 8.8%; P = .78). Systolic blood pressure and serum potassium were similar during low and high sodium intake and during aldosterone infusion. Conclusions: Low dietary sodium intake reduces insulin secretion in humans, independent of insulin sensitivity. PMID:25029426

  15. Co-immobilization of adhesive peptides and VEGF within a dextran-based coating for vascular applications.

    PubMed

    Noel, Samantha; Fortier, Charles; Murschel, Frederic; Belzil, Antoine; Gaudet, Guillaume; Jolicoeur, Mario; De Crescenzo, Gregory

    2016-06-01

    Multifunctional constructs providing a proper environment for adhesion and growth of selected cell types are needed for most tissue engineering and regenerative medicine applications. In this context, vinylsulfone (VS)-modified dextran was proposed as a matrix featuring low-fouling properties as well as multiple versatile moieties. The displayed VS groups could indeed react with thiol, amine or hydroxyl groups, be it for surface grafting, crosslinking or subsequent tethering of biomolecules. In the present study, a library of dextran-VS was produced, grafted to aminated substrates and characterized in terms of degree of VS modification (%VS), cell-repelling properties and potential for the oriented grafting of cysteine-tagged peptides. As a bioactive coating of vascular implants, ECM peptides (e.g. RGD) as well as vascular endothelial growth factor (VEGF) were co-immobilized on one of the most suitable dextran-VS coating (%VS=ca. 50% of saccharides units). Both RGD and VEGF were efficiently tethered at high densities (ca. 1nmol/cm(2) and 50fmol/cm(2), respectively), and were able to promote endothelial cell adhesion as well as proliferation. The latter was enhanced to the same extent as with soluble VEGF and proved selective to endothelial cells over smooth muscle cells. Altogether, multiple biomolecules could be efficiently incorporated into a dextran-VS construct, while maintaining their respective biological activity. This work addresses the need for multifunctional coatings and selective cell response inherent to many tissue engineering and regenerative medicine applications, for instance, vascular graft. More specifically, a library of dextrans was first generated through vinylsulfone (VS) modification. Thoroughly selected dextran-VS provided an ideal platform for unbiased study of cell response to covalently grafted biomolecules. Considering that processes such as healing and angiogenesis require multiple factors acting synergistically, vascular endothelial

  16. Astrocyte Sodium Signalling and Panglial Spread of Sodium Signals in Brain White Matter.

    PubMed

    Moshrefi-Ravasdjani, Behrouz; Hammel, Evelyn L; Kafitz, Karl W; Rose, Christine R

    2017-09-01

    In brain grey matter, excitatory synaptic transmission activates glutamate uptake into astrocytes, inducing sodium signals which propagate into neighboring astrocytes through gap junctions. These sodium signals have been suggested to serve an important role in neuro-metabolic coupling. So far, it is unknown if astrocytes in white matter-that is in brain regions devoid of synapses-are also able to undergo such intra- and intercellular sodium signalling. In the present study, we have addressed this question by performing quantitative sodium imaging in acute tissue slices of mouse corpus callosum. Focal application of glutamate induced sodium transients in SR101-positive astrocytes. These were largely unaltered in the presence of ionotropic glutamate receptors blockers, but strongly dampened upon pharmacological inhibition of glutamate uptake. Sodium signals induced in individual astrocytes readily spread into neighboring SR101-positive cells with peak amplitudes decaying monoexponentially with distance from the stimulated cell. In addition, spread of sodium was largely unaltered during pharmacological inhibition of purinergic and glutamate receptors, indicating gap junction-mediated, passive diffusion of sodium between astrocytes. Using cell-type-specific, transgenic reporter mice, we found that sodium signals also propagated, albeit less effectively, from astrocytes to neighboring oligodendrocytes and NG2 cells. Again, panglial spread was unaltered with purinergic and glutamate receptors blocked. Taken together, our results demonstrate that activation of sodium-dependent glutamate transporters induces sodium signals in white matter astrocytes, which spread within the astrocyte syncytium. In addition, we found a panglial passage of sodium signals from astrocytes to NG2 cells and oligodendrocytes, indicating functional coupling between these macroglial cells in white matter.

  17. 77 FR 50121 - Hospira, Inc.; Withdrawal of Approval of a New Drug Application for DEXTRAN 70

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-20

    ..., Center for Biologics Evaluation and Research (HFM-17), Food and Drug Administration, 1401 Rockville Pike... and Research, by the Commissioner of Food and Drugs, approval of NDA 080- 819, DEXTRAN 70 [6% Dextran... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0840...

  18. Synthesis and application of magnetite dextran-spermine nanoparticles in breast cancer hyperthermia.

    PubMed

    Avazzadeh, Reza; Vasheghani-Farahani, Ebrahim; Soleimani, Masoud; Amanpour, Saeid; Sadeghi, Mohsen

    2017-09-01

    Cancer treatment has been very challenging in recent decades. One of the most promising cancer treatment methods is hyperthermia, which increases the tumor temperature (41-45 °C). Magnetic nanoparticles have been widely used for selective targeting of cancer cells. In the present study, magnetic dextran-spermine nanoparticles, conjugated with Anti-HER2 antibody to target breast cancer cells were developed. The magnetic dextran-spermine nanoparticles (DMNPs) were prepared by ionic gelation, followed by conjugation of antibody to them using EDC-NHS method. Then the Prussian blue method was used to estimate the targeting ability and cellular uptake. Cytotoxicity assay by MTT showed that antibody-conjugated MNPs (ADMNPs) have no toxic effect on SKBR3 and human fibroblast cells. Finally, the hyperthermia was applied to show that synthesized ADMNPs, could increase the cancer cells temperature up to 45 °C and kill most of them without affecting normal cells. These observations proved that Anti-HER2 conjugated magnetic dextran-spermine nanoparticles can target and destroy cancer cells and are potentially suitable for cancer treatment.

  19. The effect of medium structure complexity on the growth of Saccharomyces cerevisiae in gelatin-dextran systems.

    PubMed

    Boons, Kathleen; Noriega, Estefanía; Verherstraeten, Niels; David, Charlotte C; Hofkens, Johan; Van Impe, Jan F

    2015-04-16

    As most food systems are (semi-)solid, the effect of food structure on bacterial growth has been widely acknowledged. However, studies on the growth dynamics of yeasts have neglected the effect of food structure. In this paper, the growth dynamics of the spoilage yeast Saccharomyces cerevisiae was investigated at 23.5 °C in broth, singular, homogeneous biopolymer systems and binary biopolymer systems with a heterogeneous microstructure. The biopolymers gelatin and dextran were used to introduce the different levels of structure. The metabolizing ability of gelatin and dextran by S. cerevisiae was examined. To study microbial behavior in the binary systems at the micro level, mixtures were imaged with confocal laser scanning microscopy (CLSM). Growth dynamics and microscopic images of S. cerevisiae were compared with those obtained for Escherichia coli in the same model system (Boons et al., 2014). Different phase-separated, heterogeneous microstructures were obtained by changing the amount of added gelatin and dextran. Regardless of the microstructure, S. cerevisiae was preferentially located in the dextran phase. Metabolizing ability-tests indicated that gelatin could be consumed by S. cerevisiae but in the presence of glucose, no change in gelatin concentration was observed. No indication of dextran metabolizing ability was observed. When supplementing broth with gelatin or dextran alone, an enhanced growth rate and maximum cell density were observed. This enhancement was further increased by adding a second biopolymer, introducing a heterogeneous microstructure and hence increasing the medium structure complexity. The results obtained indicate that food structure complexity plays a significant role in the growth dynamics of S. cerevisiae, an important food spoiler. Copyright © 2014. Published by Elsevier B.V.

  20. Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures

    USGS Publications Warehouse

    Wang, Ning; Consbrock, Rebecca A.; Ingersoll, Christopher G.; Hardesty, Douglas K.; Brumbaugh, William G.; Hammer, Edward J.; Bauer, Candice R.; Mount, David R.

    2016-01-01

    The acute and chronic toxicity of sulfate (tested as sodium sulfate) was determined in diluted well water (hardness of 100 mg/L and pH 8.2) with a cladoceran (Ceriodaphnia dubia; 2-d and 7-d exposures), a midge (Chironomus dilutus; 4-d and 41-d exposures), a unionid mussel (pink mucket, Lampsilis abrupta; 4-d and 28-d exposures), and a fish (fathead minnow, Pimephales promelas; 4-d and 34-d exposures). Among the 4 species, the cladoceran and mussel were acutely more sensitive to sulfate than the midge and fathead minnow, whereas the fathead minnow was chronically more sensitive than the other 3 species. Acute-to-chronic ratios ranged from 2.34 to 5.68 for the 3 invertebrates but were as high as 12.69 for the fish. The fathead minnow was highly sensitive to sulfate during the transitional period from embryo development to hatching in the diluted well water, and thus, additional short-term (7- to 14-d) sulfate toxicity tests were conducted starting with embryonic fathead minnow in test waters with different ionic compositions at a water hardness of 100 mg/L. Increasing chloride in test water from 10 mg Cl/L to 25 mg Cl/L did not influence sulfate toxicity to the fish, whereas increasing potassium in test water from 1mg K/L to 3mg K/L substantially reduced the toxicity of sulfate. The results indicate that both acute and chronic sulfate toxicity data, and the influence of potassium on sulfate toxicity to fish embryos, need to be considered when environmental guidance values for sulfate are developed or refined.

  1. Characterization of dextran-grafted hydrophobic charge-induction resins: Structural properties, protein adsorption and transport.

    PubMed

    Liu, Tao; Angelo, James M; Lin, Dong-Qiang; Lenhoff, Abraham M; Yao, Shan-Jing

    2017-09-29

    The structural and functional properties of a series of dextran-grafted and non-grafted hydrophobic charge-induction chromatographic (HCIC) agarose resins were characterized by macroscopic and microscopic techniques. The effects of dextran grafting and mobile phase conditions on the pore dimensions of the resins were investigated with inverse size exclusion chromatography (ISEC). A significantly lower pore radius (17.6nm) was found for dextran-grafted than non-grafted resins (29.5nm), but increased salt concentration would narrow the gap between the respective pore radii. Two proteins, human immunoglobulin G (hIgG) and bovine serum albumin (BSA), were used to examine the effect of protein characteristics. The results of adsorption isotherms showed that the dextran-grafted resin with high ligand density had substantially higher adsorption capacity and enhanced the salt-tolerance property for hIgG, but displayed a significantly smaller benefit for BSA adsorption. Confocal laser scanning microscopy (CLSM) showed that hIgG presented more diffuse and slower moving adsorption front compared to BSA during uptake into the resins because of the selective binding of multiple species from polyclonal IgG; polymer-grafting with high ligand density could enhance the rate of hIgG transport in the dextran-grafted resins without salt addition, but not for the case with high salt and BSA. The results indicate that microscopic analysis using ISEC and CLSM is useful to improve the mechanistic understanding of resin structure and of critical functional parameters involving protein adsorption and transport, which would guide the rational design of new resins and processes. Copyright © 2017. Published by Elsevier B.V.

  2. Kidney injury after sodium phosphate solution beyond the acute renal failure.

    PubMed

    Fernández-Juárez, Gema; Parejo, Leticia; Villacorta, Javier; Tato, Ana; Cazar, Ramiro; Guerrero, Carmen; Marin, Isabel Martinez; Ocaña, Javier; Mendez-Abreu, Angel; López, Katia; Gruss, Enrique; Gallego, Eduardo

    2016-01-01

    Screening colonoscopy with polipectomy reduces colonorectal cancer incidence and mortality. An adequate bowel cleansing is one of the keys to achieving best results with this technique. Oral sodium phosphate solution (OSP) had a widespread use in the 90s decade. Its efficacy was similar to polyethylene glycol (PEG) solution, but with less cost and convenient administration. Series of patients with acute renal failure due to OSP use have been reported. However, large cohorts of patients found no difference in the incidence of renal damage between these two solutions. From 2006 to 2009 we identified twelve cases of phosphate nephropathy after colonoscopy prepared with OSP. All patients were followed up to six months. All patients had received just a single dose. We analyzed 12 cases with phosphate nephropathy; three patients debuted with AKI and nine patients had chronic renal injury. Four cases were confirmed with renal biopsy. One patient with AKI needed hemodialysis at diagnosis without subsequent recovery. Two patients (both with chronic damage) fully recovered their previous renal function. The remaining patients (nine) had an average loss of estimated glomerular filtration rate of 24ml/min/1.73m(2). The use of OSP can lead to both acute and chronic renal damage. However, chronic injury was the most common pattern. Both forms of presentation imply a significant and irreversible loss of renal function. Further studies analyzing renal damage secondary to bowel cleaning should consider these two different patterns of injury. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  3. Deficiency of renal dopaminergic-dependent natriuretic response to acute sodium load in black salt-sensitive subjects in contrast to salt-resistant subjects.

    PubMed

    Damasceno, A; Santos, A; Serrão, P; Caupers, P; Soares-da-Silva, P; Polónia, J

    1999-12-01

    To evaluate the involvement of the renal dopaminergic system in the natriuretic responses to acute saline load in salt-resistant (SR) and salt-sensitive (SS) black normotensive (NT) and hypertensive (HT) subjects. We studied the relationship between the urinary excretion of dopa, dopamine (DA) and its metabolite DOPAC and the natriuretic responses to acute volume expansion (2 l NaCl 0.9% over 2 h) in 20 black NT subjects (12 SR and 8 SS) and 19 black HT subjects (10 SS and 9 SR). Subjects received a low salt (LS) diet (40 mmol sodium/day) for 1 week and a high salt (HS) diet (300 mmol sodium/day) for 1 week; the sequence of the dietary regimens was randomized. Comparisons were made between the results before the saline infusion (baseline) and the results 2 h after the infusion. In all the groups saline infusion induced significant increases in urinary volume (ml/4 h) of two- to three-fold and in urinary sodium excretion (mmol/4 h) of three- to ten-fold; these increases were significantly greater during the HS diet than during the LS diet. Saline infusion significantly increased the mean arterial pressure (MAP) by 5 mmHg in HT-SS subjects and by 4-5 mmHg in NT-SS subjects, but the MAP did not changed in the NT-SR and HT-SR groups. Under the LS diet, saline infusion changed the DA excretion (in nmol/4 h) by -49+/-89 in HT-SS subjects, by 17+/-52 in NT-SS subjects, by 235+/-72 in HT-SR subjects and by 220+/-86 in NT-SR subjects (P < 0.05 between SR and SS subjects). The saline infusion-induced changes in DA excretion correlated significantly with the increases in urinary sodium excretion (r = 0.71, P < 0.01) in the NT-SR and HT-SR subjects under the LS diet, but not in the SR groups on the HS diet nor in the SS groups (HT and NT) on either diet. Saline infusion significantly reduced the DA/dopa ratio in SS (NT and HT) but not SR (NT and HT) subjects, whereas the DA/DOPAC (dihydroxyphenylacetic acid) ratios were similar in all the groups. The urinary dopaminergic

  4. Effect of varying molecular weight of dextran on acrylic-derivatized dextran and concanavalin A glucose-responsive materials for closed-loop insulin delivery.

    PubMed

    Sahota, Tarsem; Sawicka, Kirsty; Taylor, Joan; Tanna, Sangeeta

    2011-03-01

    Dextran methacrylate (dex-MA) and concanavalin A (con A)-methacrylamide were photopolymerized to produce covalently cross-linked glucose-sensitive gels for the basis of an implantable closed-loop insulin delivery device. The viscoelastic properties of these polymerized gels were tested rheologically in the non-destructive oscillatory mode within the linear viscoelastic range at glucose concentrations between 0 and 5% (w/w). For each cross-linked gel, as the glucose concentration was raised, a decrease in storage modulus, loss modulus and complex viscosity (compared at 1 Hz) was observed, indicating that these materials were glucose responsive. The higher molecular weight acrylic-derivatized dextrans [degree of substitution (DS) 3 and 8%] produced higher complex viscosities across the glucose concentration range. These studies coupled with in vitro diffusion experiments show that dex-MA of 70 kDa and DS (3%) was the optimum mass average molar mass to produce gels that show reduced component leach, glucose responsiveness, and insulin transport useful as part of a self-regulating insulin delivery device.

  5. Acute eprosartan-induced intrarenal vasodilation in hypertensive humans is not influenced by dietary sodium intake or angiotensin II co-infusion.

    PubMed

    van Twist, Daan J L; Houben, Alfons J H M; de Leeuw, Peter W; Kroon, Abraham A

    2016-08-01

    Angiotensin II (Ang II) is thought to play an important role in the development of hypertension. Nevertheless, knowledge on the angiotensin II type-1-receptors (AT1Rs) in the hypertensive kidney and the influence of sodium intake and renin-angiotensin system activity on intrarenal AT1R blockade is scarce. To improve our understanding of renal AT1Rs in hypertensive patients, we studied the effects of acute, local administration of AT1R-blocker eprosartan in kidneys of patients with essential hypertension (off medication). In 73 hypertensive patients who were scheduled for diagnostic renal angiography, we measured renal blood flow (Xenon washout method) before and during intrarenal infusion of two incremental doses of eprosartan (3 and 10 μg/kg/min for 15 min per dose). We hypothesized that the vasodilatory effects of eprosartan would be enhanced by low sodium intake and would be reduced during Ang II co-infusion. Therefore, we allocated the patients to either a high or a low sodium diet and coinfused Ang II (1 ng/kg/min) in a subgroup. Eprosartan infusion resulted in intrarenal vasodilation in all groups. No differences in the magnitude of this effect were found between the groups. No correlation was found between 24-h urinary sodium excretion (a proxy for dietary sodium intake) and the effect of eprosartan. Eprosartan-induced vasodilation is not influenced by sodium intake and/or co-infusion of Ang II. These rather unexpected findings could be explained by differences between circulating and tissue Ang II levels, variations in AT1R expression, and/or stimulation of other vasodilatory pathways.

  6. One pot light assisted green synthesis, storage and antimicrobial activity of dextran stabilized silver nanoparticles.

    PubMed

    Hussain, Muhammad Ajaz; Shah, Abdullah; Jantan, Ibrahim; Tahir, Muhammad Nawaz; Shah, Muhammad Raza; Ahmed, Riaz; Bukhari, Syed Nasir Abbas

    2014-12-03

    Green synthesis of nanomaterials finds the edge over chemical methods due to its environmental compatibility. Herein, we report green synthesis of silver nanoparticles (Ag NPs) mediated with dextran. Dextran was used as a stabilizer and capping agent to synthesize Ag NPs using silver nitrate (AgNO3) under diffused sunlight conditions. UV-vis spectra of as synthesized Ag nanoparticles showed characteristic surface plasmon band in the range from ~405-452 nm. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) studies showed spherical Ag NPs in the size regime of ~50-70 nm. Face centered cubic lattice of Ag NPs was confirmed by powder X-ray diffraction (PXRD). FT-IR spectroscopy confirmed that dextran not only acts as reducing agent but also functionalizes the surfaces of Ag NPs to make very stable dispersions. Moreover, on drying, the solution of dextran stabilized Ag NPs resulted in the formation of thin films which were found stable over months with no change in the plasmon band of pristine Ag NPs. The antimicrobial assay of the as synthesized Ag NPs showed remarkable activity. Being significantly active against microbes, the Ag NPs can be explored for antimicrobial medical devices.

  7. Influence of molecular structure on the tolerogenicity of bacterial dextrans. I. The alpha1--6-linked epitope of dextran B512.

    PubMed Central

    Howard, J G; Vicari, G; Courtenay, B M

    1975-01-01

    Native dextran B512 is a near-linear glucose polymer with 96 per cent alpha1--6 and 4 per cent alpha1--3 linkages and a molecular weight (mol. wt) of 8 X 10(7). Sheep RBC sensitized with its O-stearoyl derivative (prepared by a modified method) have been used satisfactorily in direct PFC assays. B512 immunizes BALB/c mice optimally with doses of 1--10 mug and produces B-cell tolerance with 1 mg upwards. The specificity of the response determined by PFC inhibition analysis, is directed towards an alpha1--6-linked epitope. High dose tolerance is not preceded by immunity and is stable on cell transfer to irradiated recipients in which responsiveness becomes perceptible after 4--6 weeks. Progressive depolymerization of this polysaccharide reduces immunogenicity and tolerogenicity, both of which are extinguished when the mol. wt falls to 2 X 10(4). Optimal immunization with B512 is succeeded by partial tolerance (previously characterized by analogous levan experiments as a B-cell exhaustion process). The tolerance threshold dose of B512 is reduced 1000-fold during immunosuppression with cyclophosphamide. PFC inhibition studies supported the contention that tolerogenicity of polysaccharides is influenced by their overall binding capacities. A direct relationship between inhibitory and tolerogenic activities was found both with B512 fractions of varying mol. wt and with heterologous dextrans. The similarities between B512 and levan argue against the association of a highly branched structure with greater tolerogenicity. The effect of reducing the percentage of alpha1--6 linkages in dextrans suggests, however, that epitope density probably plays a contributory role in determining the outcome of interaction between polysaccharides and B cells. PMID:52612

  8. “Click” Synthesis of Dextran Macrostructures for Combinatorial-Designed Self-Assembled Nanoparticles Encapsulating Diverse Anticancer Therapeutics

    PubMed Central

    Abeylath, Sampath C.; Amiji, Mansoor

    2011-01-01

    With the non-specific toxicity of anticancer drugs to healthy tissues upon systemic administration, formulations capable of enhanced selectivity in delivery to the tumor mass and cells are highly desirable. Based on the diversity of the drug payloads, we have investigated a combinatorial-designed strategy where the nano-sized formulations are tailored based on the physicochemical properties of the drug and the delivery needs. Individually functionalized C2 to C12 lipid-, thiol-, and poly(ethylene glycol) (PEG)-modified dextran derivatives were synthesized via “click” chemistry from O-pentynyl dextran and relevant azides. These functionalized dextrans in combination with anticancer drugs form nanoparticles by self-assembling in aqueous medium having PEG surface functionalization and intermolecular disulfide bonds. Using anticancer drugs with logP values ranging from −0.5 to 3.0, the optimized nanoparticles formulations were evaluated for preliminary cellular delivery and cytotoxic effects in SKOV3 human ovarian adenocarcinoma cells. The results show that with the appropriate selection of lipid-modified dextran, one can effectively tailor the self-assembled nano-formulation for intended therapeutic payload. PMID:21978947

  9. Qualitative and quantitative analysis of branches in dextran using high-performance anion exchange chromatography coupled to quadrupole time-of-flight mass spectrometry.

    PubMed

    Yi, Lin; Ouyang, Yilan; Sun, Xue; Xu, Naiyu; Linhardt, Robert J; Zhang, Zhenqing

    2015-12-04

    Dextran, a family of natural polysaccharides, consists of an α (1→6) linked-glucose main (backbone) chain having a number of branches. The determination of the types and the quantities of branches in dextran is important in understanding its various biological roles. In this study, a hyphenated method using high-performance anion exchange chromatography (HPAEC) in parallel with pulsed amperometric detection (PAD) and mass spectrometry (MS) was applied to qualitative and quantitative analysis of dextran branches. A rotary cation-exchange cartridge array desalter was used for removal of salt from the HPAEC eluent making it MS compatible. MS and MS/MS were used to provide structural information on the enzymatically prepared dextran oligosaccharides. PAD provides quantitative data on the ratio of enzyme-resistant, branched dextran oligosaccharides. Both the types and degree of branching found in a variety of dextrans could be simultaneously determined online using this method. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. 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.

  11. Anticancer drug-based multifunctional nanogels through self-assembly of dextran-curcumin conjugates toward cancer theranostics.

    PubMed

    Nagahama, Koji; Sano, Yoshinori; Kumano, Takayuki

    2015-06-15

    Curcumin (CCM) has been received much attention in cancer theranostics because CCM exhibits both anticancer activity and strong fluorescence available for bio-imaging. However, CCM has never been utilized in clinical mainly due to its extremely low water solubility and its low cellular uptake into cancer cells. We fabricated novel CCM-based biodegradable nanoparticles through self-assembly of amphiphilic dextran-CCM conjugates. Significantly high CCM loading contents in the nanoparticles and the high water solubility were achieved. Importantly, the dextran-CCMs nanoparticles were effectively delivered into HeLa cells and exhibited strong fluorescence available for live-cell imaging, although the nanoparticles were not delivered into normal cells. Thus, the dextran-CCMs nanoparticles could be a promising for creation of novel CCM-based cancer theranostics with high efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. The erythrocyte sodium and potassium in patients treated with digoxin.

    PubMed Central

    Morgan, D B; Cumberbatch, M; Cohn, S; Scott, D; Gunasuntharam, T; Davidson, C; Chapman, C

    1980-01-01

    1 Four healthy persons and ten patients with heart failure were studied for 5 to 20 days after they started taking digoxin. The sodium content of their erythrocytes increased and there was an equimolar decrease in potassium content. 2 The increase in erythrocyte sodium for a given increase in plasma digoxin during this acute digitalization was less on average and varied more in the patients than in the healthy persons, that is the patients' erythrocytes were less responsive to digoxin. 3 The average erythrocyte sodium was greater in 183 patients who had been taking digoxin for at least 2 months than in 100 healthy persons not taking digoxin but there was no significant correlation between the plasma digoxin concentrations and erythrocyte sodium concentration in the patients. Indeed, there was no apparent change in the erythrocyte sodium in many of the patients taking digoxin. 4 If the erythrocyte sodium concentration is a reliable guide to the tissue effects of digoxin then the results suggest that there is a wide variation in the response to digoxin between patients both during acute digitalization and during chronic treatment with digoxin. PMID:7426274

  13. Chromatography of Penicillins, Penicilloates, and Penicilloylamides on Dextran Gels

    PubMed Central

    Hyslop, Newton E.; Milligan, Richard J.

    1974-01-01

    The factors influencing the chromatographic behavior on dextran gels of penicillins and their derivatives were investigated by comparing elution profiles and partition coefficients (KD and KAV) of penicillins differing in side-chain structure and among penicillin derivatives of identical side-chain but different nuclear structure. Under the conditions of pH and ionic strength employed (pH 7.4, 0.145 M NaCl, 0.05 M PO4), side-chain adsorptive effects best explained the anomalous behavior of benzylpenicillin and of oxacillin and its chlorine-substituted analogues. Polar side-chain substituents, such as the amino group of ampicillin and the carboxyl group of carbenicillin, and cleavage of the β-lactam ring, exemplified by penicilloates and penicilloylamines, both appeared to interfere with side-chain-directed adsorption. The differential adsorption of penicillins and their derivatives to dextran gels is not only of theoretical interest relative to the mechanism of chromatography but of practical application to analytical and preparative procedures in penicillin chemistry. PMID:15825415

  14. Effects of sodium in hydration solution on plasma methotrexate concentrations following high-dose methotrexate in children with acute lymphoblastic leukemia.

    PubMed

    Kinoshita, Akitoshi; Kurosawa, Yoshihiro; Kondoh, Kensuke; Suzuki, Toshio; Manabe, Atsushi; Inukai, Takeshi; Sugita, Kanji; Nakazawa, Shinpei

    2003-03-01

    To test whether a higher sodium dose in the hydration solution may facilitate faster methotrexate (MTX) elimination as compared with a lower sodium dose following high-dose MTX (HDMTX) treatment. Intravenous solutions with alternate doses of sodium (regimen A 70 mEq/l, regimen B 100 mEq/l) were given to 30 children with acute lymphoblastic leukemia in two courses of HDMTX in a randomized crossover fashion. The plasma MTX concentrations every 24 h from the beginning of MTX administration and the adverse events associated with HDMTX were compared between the two hydration regimens. The plasma MTX concentrations were similar in the two hydration regimens at 24 h (A 50.9+/-7.4 vs B 40.9+/-5.4 microM, means+/- SE, P=0.17), but was significantly lower in regimen B at 48 and 72 h (A 0.65+/-0.17 vs B 0.27+/-0.03 microM, P=0.04; and A 0.14+/-0.03 vs B 0.05+/-0.01 microM, P=0.003). The time during which MTX plasma concentrations exceeded 0.1 microM was significantly longer in regimen A than in regimen B (A 3.83+/-0.18 vs B 3.13+/-0.06 days, P=0.001). The incidences of adverse events were similar between the two regimens ( P=0.78), and severe adverse events were not seen in either regimen. Hydration with a higher sodium dose facilitated faster MTX elimination following HDMTX. Sodium may have a beneficial effect on MTX-induced nephrotoxicity.

  15. Trans fatty acids exacerbate dextran sodium sulphate-induced colitis by promoting the up-regulation of macrophage-derived proinflammatory cytokines involved in T helper 17 cell polarization.

    PubMed

    Okada, Y; Tsuzuki, Y; Sato, H; Narimatsu, K; Hokari, R; Kurihara, C; Watanabe, C; Tomita, K; Komoto, S; Kawaguchi, A; Nagao, S; Miura, S

    2013-12-01

    Numerous reports have shown that a diet containing large amounts of trans fatty acids (TFAs) is a major risk factor for metabolic disorders. Although recent studies have shown that TFAs promote intestinal inflammation, the underlying mechanisms are unknown. In this study, we examined the effects of dietary fat containing TFAs on dextran sodium sulphate (DSS)-induced colitis. C57 BL/6 mice were fed a diet containing 1·3% TFAs (mainly C16:1, C18:1, C18:2, C20:1, C20:2 and C22:1), and then colitis was induced with 1·5% DSS. Colonic damage was assessed, and the mRNA levels of proinflammatory cytokines and major regulators of T cell differentiation were measured. The TFA diet reduced survival and exacerbated histological damage in mice administered DSS compared with those fed a TFA-free diet. The TFA diet significantly elevated interleukin (IL)-6, IL-12p40, IL-23p19 and retinoic acid-related orphan receptor (ROR)γt mRNA levels in the colons of DSS-treated animals. Moreover, IL-17A mRNA levels were elevated significantly by the TFA diet, with or without DSS treatment. We also examined the expression of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and peritoneal macrophages. These cells were exposed to TFAs (linoelaidic acid or elaidic acid) with or without LPS and the mRNA levels of various cytokines were measured. IL-23p19 mRNA levels were increased significantly by TFAs in the absence of LPS. Cytokine expression was also higher in LPS-stimulated cells exposed to TFAs than in unexposed LPS-stimulated cells. Collectively, our results suggest that TFAs exacerbate colonic inflammation by promoting Th17 polarization and by up-regulating the expression of proinflammatory cytokines in the inflamed colonic mucosa. © 2013 British Society for Immunology.

  16. Mold Pectinase Modified with Dialdehyde Derivatives of Dextran and Cellulose.

    PubMed

    Kobayashi, M; Chiba, Y; Funane, K; Ohya, S; Kato, Y

    1996-01-01

    Chemical modification of mold pectinase with dextran- and cellulose-dialdehydes was examined to improve the enzyme characteristics. The modified pectinase with dextran-dialdehyde retained about 50% of the original activity, and more than 80% of the total amino groups were modified. HPLC gel filtration analysis showed an increase in molecular weight of the reaction product. Reaction with cellulose-dialdehyde provided an immobilized form of pectinase. The immobilized pectinase was resistant to both acidic and alkaline pHs, and also acquired heat stability at 60°C. The optimum pH of the modified enzyme shifted from pH 4.5 to 5.0-5.5, and this enzyme had higher activity at neutral pH regions than the native enzyme. A rather low recovery of immobilized enzyme (14.5%) should be improved by the combination with various methods hitherto established.

  17. [Protective effect of Uncaria rhynchophylla total alkaloids pretreatment on hippocampal neurons after acute hypoxia].

    PubMed

    Liu, Wei; Zhang, Zhao-qin; Zhao, Xiao-min; Gao, Yun-sheng

    2006-05-01

    To investigate the effect of Uncaria rhynchophylla total alkaloids (RTA) pretreatment on the voltage-gated sodium currents of the rat hippocampal neurons after acute hypoxia. Primary cultured hippocampal neurons were divided into RTA pre-treated and non-pretreated groups. Patch clamp whole-cell recording was used to compare the voltage-gated sodium current amplitude and threshold with those before hypoxia. After acute hypoxia, sodium current amplitude was significantly decreased and its threshold was upside. RTA pretreatment could inhibit the reduction of sodium current amplitude. RTA pretreatment alleviates the acute hypoxia-induced change of sodium currents, which may be one of the mechanisms for protective effect of RTA on cells.

  18. Fatal cases of acute suicidal sodium and accidental zinc fluorosilicate poisoning. Review of acute intoxications due to fluoride compounds.

    PubMed

    Lech, Teresa

    2011-03-20

    Fluoride, of all inorganic substances, is among the least likely to be identified by a routine toxicological analysis. Acute poisonings with salts of hydrofluoric or fluorosilicic acid, however, although relatively uncommon, may occur. Some fluorosilicates, salts of fluorosilicic acid (e.g. Al, Zn, Pb, Mg) are used as stone consolidants, others (e.g. sodium fluorosilicate)--in the production of enamel and milk glass, or as insecticide. In this paper, two fatal cases of poisonings are presented: a suicide involving sodium fluorosilicate of a 39-year-old male who died in his flat, without hospitalization, and an accidental ingestion of zinc fluorosilicate solution (probably due to mistaking it for mineral water) by a 38-year-old male at his workplace (building), who died about 3h after ingestion of the liquid, in spite of intensive care at hospitals. Post-mortem samples were examined by the use of the spectrophotometric method with lanthanum nitrate and alizarin complexone for fluorine (after isolation of fluoride compounds by the microdiffusion method) and using a flame atomic absorption spectrometry method for zinc (after mineralization of biological material by sulfuric and nitric acids). In the first case, the results were: blood--130 μg F/ml, stomach--1150 μg F/g, small intestine content --19.6 μg F/g, kidney--56.0 μg F/g, and urine--1940 μg F/ml. In the second case, the contents of fluorine and zinc in blood and internal organs were the following: blood--6.03 μg F/ml, 23.8 μg Zn/ml; brain--1.39 μg F/g, 7.54 μg Zn/g; stomach--152 μg Zn/g; stomach content--293 μg F/g, 84.4 μg Zn/g; small intestine--37.5 μg Zn/g; small intestine content--63.4 μg F/g, 19.6 μg Zn/g; liver--9.49 μg F/g, 81.0 μg Zn/g; kidney--29.6 μg F/g, 39.2 μg Zn/g; and exceeded the normal levels of these elements in biological material many times. In addition, in stomach and liver large amounts of silica were detected. In the paper, a review of acute intoxications with various

  19. Permeability of the Peritrophic Envelopes of Herbivorous Insects to Dextran Sulfate: a Test of the Polyanion Exclusion Hypothesis.

    PubMed

    MARTIN, M M.; BARBEHENN, R V.

    1997-03-01

    We tested the hypothesis that the permeability of the peritrophic envelope in herbivorous insects is greatly reduced for polyanions as a result of an extensive network of anionic sites in the proteoglycans of the matrix. 14C-Dextran sulfate (polyanionic, 8000 M(w)) and fluorescein isothiocyanate-labeled (FITC) dextran (monoanionic, 9400 M(w)) were introduced together into the endoperitrophic space of the midguts of Orgyia leucostigma (Lepidoptera) larvae and Melanoplus sanguinipes (Orthoptera) adults. In all cases more of the 14C-dextran sulfate permeated the peritrophic envelope than the FITC-dextran, the opposite of the result predicted by the polyanion exclusion hypothesis. We conclude that polyanion exclusion is not a mechanism that contributes significantly to the permeability properties of the peritrophic envelopes of these two species, or that explains the failure of tannic acid to cross the peritrophic envelopes of lepidopteran larvae. Copyright 1997 Elsevier Science Ltd. All rights reserved

  20. Anti-inflammatory effects of the selective phosphodiesterase 3 inhibitor, cilostazol, and antioxidants, enzymatically-modified isoquercitrin and α-lipoic acid, reduce dextran sulphate sodium-induced colorectal mucosal injury in mice.

    PubMed

    Kangawa, Yumi; Yoshida, Toshinori; Abe, Hajime; Seto, Yoshiki; Miyashita, Taishi; Nakamura, Michi; Kihara, Tohru; Hayashi, Shim-Mo; Shibutani, Makoto

    2017-04-04

    Developing effective treatments and preventing inflammatory bowel disease (IBD) are urgent challenges in improving patients' health. It has been suggested that platelet activation and reactive oxidative species generation are involved in the pathogenesis of IBD. We examined the inhibitory effects of a selective phosphodiesterase-3 inhibitor, cilostazol (CZ), and two antioxidants, enzymatically modified isoquercitrin (EMIQ) and α-lipoic acid (ALA), against dextran sulphate sodium (DSS)-induced colitis. BALB/c mice were treated with 0.3% CZ, 1.5% EMIQ, and 0.2% ALA in their feed. Colitis was induced by administering 5% DSS in drinking water for 8days. The inhibitory effects of these substances were evaluated by measuring relevant clinical symptoms (faecal blood, diarrhoea, and body weight loss), colon length, plasma cytokine and chemokine levels, whole genome gene expression, and histopathology. Diarrhoea was suppressed by each treatment, while CZ prevented shortening of the colon length. All treatment groups exhibited decreased plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α compared with the DSS group. Microarray analysis showed that cell adhesion, cytoskeleton regulation, cell proliferation, and apoptosis, which might be related to inflammatory cell infiltration and mucosal healing, were affected in all the groups. DSS-induced mucosal injuries such as mucosal loss, submucosal oedema, and inflammatory cell infiltration in the distal colon were prevented by CZ or antioxidant treatment. These results suggest that anti-inflammatory effects of these agents reduced DSS-induced mucosal injuries in mice and, therefore, may provide therapeutic benefits in IBD. Copyright © 2016 Elsevier GmbH. All rights reserved.

  1. Characterization of the dextran-binding domain in the glucan-binding protein C of Streptococcus mutans.

    PubMed

    Takashima, Y; Fujita, K; Ardin, A C; Nagayama, K; Nomura, R; Nakano, K; Matsumoto-Nakano, M

    2015-10-01

    Streptococcus mutans produces multiple glucan-binding proteins (Gbps), among which GbpC encoded by the gbpC gene is known to be a cell-surface-associated protein involved in dextran-induced aggregation. The purpose of the present study was to characterize the dextran-binding domain of GbpC using bioinformatics analysis and molecular techniques. Bioinformatics analysis specified five possible regions containing molecular binding sites termed GB1 through GB5. Next, truncated recombinant GbpC (rGbpC) encoding each region was produced using a protein expression vector and five deletion mutant strains were generated, termed CDGB1 through CDGB5 respectively. The dextran-binding rates of truncated rGbpC that included the GB1, GB3, GB4 and GB5 regions in the upstream sequences were higher than that of the construct containing GB2 in the downstream region. In addition, the rates of dextran-binding for strains CDGB4 and CD1, which was entire gbpC deletion mutant, were significantly lower than for the other strains, while those of all other deletion mutants were quite similar to that of the parental strain MT8148. Biofilm structures formed by CDGB4 and CD1 were not as pronounced as that of MT8148, while those formed by other strains had greater density as compared to that of CD1. Our results suggest that the dextran-binding domain may be located in the GB4 region in the interior of the gbpC gene. Bioinformatics analysis is useful for determination of functional domains in many bacterial species. © 2015 The Society for Applied Microbiology.

  2. Tuning complement activation and pathway through controlled molecular architecture of dextran chains in nanoparticle corona.

    PubMed

    Coty, Jean-Baptiste; Eleamen Oliveira, Elquio; Vauthier, Christine

    2017-11-05

    The understanding of complement activation by nanomaterials is a key to a rational design of safe and efficient nanomedicines. This work proposed a systematic study investigating how molecular design of nanoparticle coronas made of dextran impacts on mechanisms that trigger complement activation. The nanoparticles used for this work consisted of dextran-coated poly(isobutylcyanoacrylate) (PIBCA) nanoparticles have already been thoroughly characterized. Their different capacity to trigger complement activation established on the cleavage of the protein C3 was also already described making these nanoparticles good models to investigate the relation between the molecular feature of their corona and the mechanism by which they triggered complement activation. Results of this new study show that complement activation pathways can be selected by distinct architectures formed by dextran chains composing the nanoparticle corona. Assumptions that explain the relation between complement activation mechanisms triggered by the nanoparticles and the nanoparticle corona molecular feature were proposed. These results are of interest to better understand how the design of dextran-coated nanomaterials will impact interactions with the complement system. It can open perspectives with regard to the selection of a preferential complement activation pathway or prevent the nanoparticles to activate the complement system, based on a rational choice of the corona configuration. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular Vesicles.

    PubMed

    Wang, Jiong-Wei; Zhang, Ya-Nan; Sze, Siu Kwan; van de Weg, Sander M; Vernooij, Flora; Schoneveld, Arjan H; Tan, Sock-Hwee; Versteeg, Henri H; Timmers, Leo; Lam, Carolyn S P; de Kleijn, Dominique P V

    2017-12-29

    Plasma extracellular vesicles (EVs) are lipid membrane vesicles involved in several biological processes including coagulation. Both coagulation and lipid metabolism are strongly associated with cardiovascular events. Lowering very-low- and low-density lipoprotein ((V)LDL) particles via dextran sulphate LDL apheresis also removes coagulation proteins. It remains unknown, however, how coagulation proteins are removed in apheresis. We hypothesize that plasma EVs that contain high levels of coagulation proteins are concomitantly removed with (V)LDL particles by dextran sulphate apheresis. For this, we precipitated (V)LDL particles from human plasma with dextran sulphate and analyzed the abundance of coagulation proteins and EVs in the precipitate. Coagulation pathway proteins, as demonstrated by proteomics and a bead-based immunoassay, were over-represented in the (V)LDL precipitate. In this precipitate, both bilayer EVs and monolayer (V)LDL particles were observed by electron microscopy. Separation of EVs from (V)LDL particles using density gradient centrifugation revealed that almost all coagulation proteins were present in the EVs and not in the (V)LDL particles. These EVs also showed a strong procoagulant activity. Our study suggests that dextran sulphate used in LDL apheresis may remove procoagulant EVs concomitantly with (V)LDL particles, leading to a loss of coagulation proteins from the blood.

  4. The Efficacy of Dextran-40 as a Venous Thromboembolism Prophylaxis Strategy in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

    PubMed

    Foster, Jason M; Sleightholm, Richard; Watley, Duncan; Wahlmeier, Steven; Patel, Asish

    2017-02-01

    The incidence of venous thromboembolism (VTE) in peritoneal malignancies can approach 30 to 50 per cent without prophylaxis. Prophylaxis in cytoreductive surgeries (CRS) presents a challenge to preoperative heparin-based therapy because of an increased risk of coagulopathy and potential for bleeding. Herein, we report the large series of CRS and hyperthermic intraperitoneal chemotherapy receiving dextran-40 prophylaxis. Retrospective chart review of peritoneal malignancies patients undergoing CRS at University of Nebraska Medical Center identified 69 individuals who received dextran-40 between 2010 and 2013. The incidences of VTEs, perioperative bleeding, complications, morbidity, and mortality were determined in-hospital and at 90 days. Of the 69 patients treated, the 30-day VTE rate was 8.7 per cent, and no pulmonary embolisms, bleeding, anaphylactoid reaction, or mortality were observed with dextran usage. The specific VTE events included three upper extremity and three lower extremity VTEs. No additional VTE events were identified between 30 and 90 days. In conclusion, dextran-40 prophylaxis was not associated with any perioperative bleeding events, and the observed incidence of VTE was comparable to reported heparin-based prophylaxis in CRS/hyperthermic intraperitoneal chemotherapy patients. This data supports further exploration of dextran-40 as a VTE prophylactic agent in complex surgical oncology cases.

  5. Simulation of the effect of hydrogen bonds on water activity of glucose and dextran using the Veytsman model.

    PubMed

    De Vito, Francesca; Veytsman, Boris; Painter, Paul; Kokini, Jozef L

    2015-03-06

    Carbohydrates exhibit either van der Waals and ionic interactions or strong hydrogen bonding interactions. The prominence and large number of hydrogen bonds results in major contributions to phase behavior. A thermodynamic framework that accounts for hydrogen bonding interactions is therefore necessary. We have developed an extension of the thermodynamic model based on the Veytsman association theory to predict the contribution of hydrogen bonds to the behavior of glucose-water and dextran-water systems and we have calculated the free energy of mixing and its derivative leading to chemical potential and water activity. We compared our calculations with experimental data of water activity for glucose and dextran and found excellent agreement far superior to the Flory-Huggins theory. The validation of our calculations using experimental data demonstrated the validity of the Veytsman model in properly accounting for the hydrogen bonding interactions and successfully predicting water activity of glucose and dextran. Our calculations of the concentration of hydrogen bonds using the Veytsman model were instrumental in our ability to explain the difference between glucose and dextran and the role that hydrogen bonds play in contributing to these differences. The miscibility predictions showed that the Veytsman model is also able to correctly describe the phase behavior of glucose and dextran. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Dextran based Polymeric Micelles as Carriers for Delivery of Hydrophobic Drugs.

    PubMed

    Mocanu, Georgeta; Nichifor, Marieta; Sacarescu, Liviu

    2017-01-01

    The improvement of drugs bioavailability, especially of the hydrophobic ones, by using various nanoparticles is a very exciting field of the modern research. The applicability of nano-sized shell crosslinked micelles based on dextran as supports for controlled release of several hydrophobic drugs (nystatin, rifampicin, resveratrol, and curcumin) was investigated by in vitro drug loading/release experiments. The synthesized crosslinked micelles were loaded with drugs of various hydrophobicities and their retention/release behavior was followed by dialysis procedure. Crosslinked micelles obtained from dextran with octadecyl end groups, with or without N-(2- hydroxypropyl)-N,N-dimethyl-N-benzylammonium chloride groups attached to the main dextran chains, could retain the drugs in amounts which increased with increasing drug hydrophobicity (water insolubility), as follows: 30-60 mg rifampicin/g, 70-100 mg nystatin/g, 120-144 mg resveratrol/g and 146-260 mg curcumin/g. The rate of drug release from the loaded micelles was also dependent on the drug hydrophobicity and was always slower than the free drug recovery. Antioxidant activity of curcumin and resveratrol released from the loaded micelles was preserved. The results highlighted the potential of the new nano-sized micelles as carriers for prolonged and controlled delivery of various hydrophobic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Recombination Between Guanidine-resistant and Dextran Sulfate-resistant Mutants of Type 1 Poliovirus

    PubMed Central

    Sergiescu, Dina; Aubert-Combiescu, Andrei; Crainic, Radu

    1969-01-01

    Mixed infection of monkey kidney cells with two mutants of the LSc2ab strain of poliovirus, one resistant to guanidine and the other resistant to both dextran sulfate and 2-(α-hydroxybenzyl)-benzimidazole (HBB), yielded progeny in which the number of guardexr particles exceeded by a factor of 7 to 10 the expected number of similar particles occurring through spontaneous mutation; recombination would explain the fairly high excess of doubly mutant particles that was obtained. Scoring of HBB resistance in 50 guardexr clones suggested that, during recombination, resistance to dextran sulfate is not associated with HBB resistance. Images PMID:4305674

  8. 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.

  9. LTβR expression on hematopoietic cells regulates acute inflammation and influences maturation of myeloid subpopulations.

    PubMed

    Wege, Anja K; Huber, Barbara; Wimmer, Nadin; Männel, Daniela N; Hehlgans, Thomas

    2014-07-01

    Lymphotoxin beta-receptor (LTβR) is involved in the formation and maintenance of secondary lymphoid structures, as well as in the regulation of inflammatory responses. Because LTβR lymphoid structure formation continues to develop in infants, we compared two different chimera models: one using adult mice and the other using a transplantation model of neonatal mice. To elucidate the function of LTβR on lymphoid and non-lymphoid cells, we generated bone marrow chimeras on the wild type C57Bl/6 and the LTβR-deficient (LTβR(-/-)) background, and reconstituted the mice with bone marrow cells reciprocally. These chimeric mice were analyzed in the experimental model of acute dextran sulfate sodium-induced colitis. Interestingly, both models revealed not only equal reconstitution levels but also similar immunological responses: LTβR expression on stromal cells is essential for lymph node formation, whereas LTBR on hematopoietic cells is crucial for a decrease in inflammation. In addition, mice lacking LTβR on hematopoietic cells revealed (a) an increase of immature granulocytic cells in the spleen and (b) a reduced proportion of myeloid cells in peripheral blood and spleen expressing CD11b(+)Ly6C(+)Ly6G(-) (myeloid-derived suppressor cells expression profile). In conclusion, LTβR expression on hematopoietic cells seems to be involved in the down-regulation of acute inflammatory reactions paralleled by the appearance of immature myeloid cells. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  10. SMU.940 regulates dextran-dependent aggregation and biofilm formation in Streptococcus mutans.

    PubMed

    Senpuku, Hidenobu; Yonezawa, Hideo; Yoneda, Saori; Suzuki, Itaru; Nagasawa, Ryo; Narisawa, Naoki

    2018-02-01

    The oral bacterium Streptococcus mutans is the principal agent in the development of dental caries. Biofilm formation by S. mutans requires bacterial attachment, aggregation, and glucan formation on the tooth surface under sucrose supplementation conditions. Our previous microarray analysis of clinical strains identified 74 genes in S. mutans that were related to biofilm morphology; however, the roles of almost all of these genes in biofilm formation are poorly understood. We investigated the effects of 21 genes randomly selected from our previous study regarding S. mutans biofilm formation, regulation by the complement pathway, and responses to competence-stimulating peptide. Eight competence-stimulating peptide-dependent genes were identified, and their roles in biofilm formation and aggregation were examined by mutational analyses of the S. mutansUA159 strain. Of these eight genes, the inactivation of the putative hemolysin III family SMU.940 gene of S. mutansUA159 promoted rapid dextran-dependent aggregation and biofilm formation in tryptic soy broth without dextrose (TSB) with 0.25% glucose and slightly reduced biofilm formation in TSB with 0.25% sucrose. The SMU.940 mutant showed higher expression of GbpC and gbpC gene than wild-type. GbpC is known to be involved in the dextran-dependent aggregation of S. mutans. An SMU.940-gbpC double mutant strain was constructed in the SMU.940 mutant background. The gbpC mutation completely abolished the dextran-dependent aggregation of the SMU.940 mutant. In addition, the aggregation of the mutant was abrogated by dextranase. These findings suggest that SMU.940 controls GbpC expression, and contributes to the regulation of dextran-dependent aggregation and biofilm formation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Comparison of Dextran Perfusion and GSI-B4 Isolectin Staining in a Mouse Model of Oxygen-induced Retinopathy.

    PubMed

    Huang, Shaofen; Liang, Jiajian; Yam, Gary Hin-Fai; Lu, Zhihao; Pang, Chi Pui; Chen, Haoyu

    2015-06-01

    Oxygen-induced retinopathy (OIR) is a robust and widely used animal model for the study of retinal neovascularization (NV). Dextran perfusion and Griffonia simplicifolia isolectin B4 (GSI-B4) staining are two common methods for examining the occurrence and extent of OIR. This study provides a quantitative comparison of the two for OIR detection. At postnatal day 7 (PN7), fifteen C57BL/6J mice were exposed to a 75% hyperoxic condition for 5 days and then returned to room air conditions. At PN17, the mice received intravitreal injection of GSI-B4 Alexa Fluor 568 conjugate. After 10 hours, they were infused with FITC-dextran conjugate via the left ventricle. Retinal flat mounts were photographed by confocal microscopy. Areas with fluorescent signals and the total retinal areas were quantified by Image J software. Both GSI-B4 and dextran detected the peripheral neovascular area. The mean hyper fluorescence area was 0.33 ± 0.14% of whole retinal area determined by GSI-B4 staining and 0.25 ± 0.28% determined by dextran perfusion. The difference between the two measures was 0.08% (95% CI:-0.59%, 0.43%). The Pearson correlation coefficient between the two methods was 0.386,P =0.035. The mean coincidence rates were 14.3 ± 13.4% and 24.9 ± 18.5% for GSI-B4 and dextran staining, respectively. Both methods can complement each other in demonstrating and quantitatively evaluating retinal NV. A poor agreement was found between the two methods; GSI-B4 isolectin was more effective than FITC-dextran perfusion in evaluating the extent of retinal NV in a mouse model of OIR.

  12. Perilymph Kinetics of FITC-Dextran Reveals Homeostasis Dominated by the Cochlear Aqueduct and Cerebrospinal Fluid.

    PubMed

    Salt, A N; Gill, R M; Hartsock, J J

    2015-06-01

    Understanding how drugs are distributed in perilymph following local applications is important as local drug therapies are increasingly used to treat disorders of the inner ear. The potential contribution of cerebrospinal fluid (CSF) entry to perilymph homeostasis has been controversial for over half a century, largely due to artifactual contamination of collected perilymph samples with CSF. Measures of perilymph flow and of drug distribution following round window niche applications have both suggested a slow, apically directed flow occurs along scala tympani (ST) in the normal, sealed cochlea. In the present study, we have used fluorescein isothiocyanate-dextran as a marker to study perilymph kinetics in guinea pigs. Dextran is lost from perilymph more slowly than other substances so far quantified. Dextran solutions were injected from pipettes sealed into the lateral semicircular canal (SCC), the cochlear apex, or the basal turn of ST. After varying delays, sequential perilymph samples were taken from the cochlear apex or lateral SCC, allowing dextran distribution along the perilymphatic spaces to be quantified. Variability was low and findings were consistent with the injection procedure driving volume flow towards the cochlear aqueduct, and with volume flow during perilymph sampling driven by CSF entry at the aqueduct. The decline of dextran with time in the period between injection and sampling was consistent with both a slow volume influx of CSF (~30 nL/min) entering the basal turn of ST at the cochlear aqueduct and a CSF-perilymph exchange driven by pressure-driven fluid oscillation across the cochlear aqueduct. Sample data also allowed contributions of other processes, such as communications with adjacent compartments, to be quantified. The study demonstrates that drug kinetics in the basal turn of ST is complex and is influenced by a considerable number of interacting processes.

  13. Hydroxyethyl starch as a substitute for dextran 40 for thawing peripheral blood progenitor cell products.

    PubMed

    Zhu, Fenlu; Heditke, Sarah; Kurtzberg, Joanne; Waters-Pick, Barbara; Hari, Parameswaran; Margolis, David A; Keever-Taylor, Carolyn A

    2015-12-01

    Removing DMSO post-thaw results in: reduced infusion reactions, improved recovery and stability of viable CD34+ cells. Validated methods use 5%-8.3% Dextran 40 with 2.5%-4.2% HSA for this purpose. Recent shortages of clinical grade Dextran require identification of suitable alternatives. PBPC were used to compare a standard 2X wash medium of 5 parts 10% Dextran 40 in saline (DEX) with 1 part 25% HSA (8.3% DEX/ 4.2% HSA) with Hydroxyethyl Starch (HES)-based solutions. Cells in replicate bags were diluted with an equal volume of wash solution, equilibrated 5 minutes, the bag filled with wash medium, pelleted and the supernatant expressed. Bags were restored to the frozen volume in wash medium and tested by single platform flow cytometry and CFU. Total viability, viable TNC, MNC, and CD34+ cell recovery, and CD34+ cell viability were compared immediately post-thaw and after 90 minutes. 5.2% HES/4.2% HSA did not differ from our standard in CD34 recovery or viability. Due to concerns that high concentrations of HES could affect renal function we tested 0.6% HES/2.5% HSA resulting in significantly poorer CD34 recovery and viability. Results improved using 2.4% HES/4.2% HSA and when 0.6% HES/4.2%HSA was used no significant differences were seen. CFU assays confirmed no differences between the standard dextran arm and HES at 2.4% or 0.6% so long as HSA was at 4.2%. We conclude that HES from 0.6% to 5.2% with 4.2% HSA is a suitable substitute for Dextran 40 as a reconstitution/washing medium for PBPC products. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  14. Anaphylaxis due to thiopental sodium anesthesia.

    PubMed Central

    Dolovich, J; Evans, S; Rosenbloom, D; Goodacre, R; Rafajac, F O

    1980-01-01

    Anaphylaxis due to an anesthetic is one type of cardiovascular emergency that can occur during general anesthesia. Anaphylactic reactions to muscle relaxants have been documented. Barbiturates, used as sedatives, are well known to produce cutaneous reactions, but anaphylaxis after their ingestion seems to be rare. Generalized allergic reactions to thiopental sodium during anesthesia are mentioned in the product monograph for Penthothal sodium, and rare case reports of anaphylactic reactions to infused thiopental have appeared, generally in the anesthesiology literature. Documentation of the immunologic responses to thiopental sodium has been limited to the demonstration of an allergic reaction to thiopental by skin testing in some cases. This report describes a woman who, after having tolerated thiopental sodium and other general anesthetics, became sensitive to this agent and had a severe acute reaction at the time of induction of general anesthesia. PMID:6167340

  15. In vivo administration of fluorescent dextrans for the specific and sensitive localization of brain vascular pericytes and their characterization in normal and neurotoxin exposed brains.

    PubMed

    Sarkar, Sumit; Schmued, Larry

    2012-06-01

    We have aimed to develop novel histochemical markers for the labeling of brain pericytes and characterize their morphology in the normal and the excitotoxin-exposed brain, as this class of cells has received little attention until recently. Pericyte labeling was accomplished by the intracerebroventricular injection of certain fluorescent dextran conjugates, such as Fluoro-Gold-dextran, FR-dextran, FITC-dextran and Fluoro-Turquoise (FT)-dextran. 1-7 days after the tracer injection, extensive labeling of vascular pericytes was seen throughout the entire brain. These cells were found distal to the endothelial cells and exhibited large dye containing vacuoles. The morphology of the pericytes was somewhat variable, exhibiting round or amoeboid shapes within larger intracellular vesicles, while those wrapping around capillaries exhibited a more elongated appearance with finger-like projections. The use of FG-dextran resulted in bluish yellow fluorescently labeled pericytes, while FR-dextran resulted in red fluorescent labeled pericytes, FITC-dextran exhibited green fluorescent pericytes and FT-dextran showed fluorescent blue pericytes in the brain. We have used these tracers to study possible changes in morphology and pericyte number following kainic acid insult, observing that the number of pericytes in the injured or lesioned areas of the brain is dramatically reduced compared to the non-injured areas. These novel fluorochromes should be of use for studies involving the detection and localization of pericytes in both normal and pathological brain tissues. Published by Elsevier B.V.

  16. Arctigenin but not arctiin acts as the major effective constituent of Arctium lappa L. fruit for attenuating colonic inflammatory response induced by dextran sulfate sodium in mice.

    PubMed

    Wu, Xin; Yang, Yan; Dou, Yannong; Ye, Jun; Bian, Difei; Wei, Zhifeng; Tong, Bei; Kong, Lingyi; Xia, Yufeng; Dai, Yue

    2014-12-01

    The crude powder of the fruit of Arctium lappa L. (ALF) has previously been reported to attenuate experimental colitis in mice. But, its main effective ingredient and underlying mechanisms remain to be identified. In this study, ALF was extracted with ethanol, and then successively fractionated into petroleum ether, ethyl acetate, n-butanol and water fraction. Experimental colitis was induced by dextran sulfate sodium (DSS) in mice. Among the four fractions of ALF, the ethyl acetate fraction showed the most significant inhibition of DSS-induced colitis in mice. The comparative studies of arctigenin and arctiin (the two main ingredients of ethyl acetate fraction) indicated that arctigenin rather than arctiin could reduce the loss of body weight, disease activity index and histological damage in the colon. Arctigenin markedly recovered the loss of intestinal epithelial cells (E-cadherin-positive cells) and decreased the infiltration of neutrophils (MPO-positive cells) and macrophages (CD68-positive cells). Arctigenin could down-regulate the expressions of TNF-α, IL-6, MIP-2, MCP-1, MAdCAM-1, ICAM-1 and VCAM-1 at both protein and mRNA levels in colonic tissues. Also, it markedly decreased the MDA level, but increased SOD activity and the GSH level. Of note, the efficacy of arctigenin was comparable or even superior to that of the positive control mesalazine. Moreover, it significantly suppressed the phosphorylation of MAPKs and the activation of NF-κB, including phosphorylation of IκBα and p65, p65 translocation and DNA binding activity. In conclusion, arctigenin but not arctiin is the main active ingredient of ALF for attenuating colitis via down-regulating the activation of MAPK and NF-κB pathways. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Effect of preparation conditions on properties and permeability of chitosan-sodium hexametaphosphate capsules.

    PubMed

    Angelova, N; Hunkeler, D

    2001-01-01

    Capsules were obtained by interpolymer complexation between chitosan (polycation) and sodium hexametaphosphate (SMP, oligoanion). The effect of the preparation conditions on the capsule characteristics was evaluated. Specifically, the influence of variables such as pH, ionic strength, reagent concentration, and additives on the capsule permeability properties was investigated using dextran as a model permeant. The capsule membrane permeability was found to increase by decreasing the chitosan/SMP ratio as well as adding mannitol to the oligoanion recipient bath. Increasing the ionic strength or the pH of the initial chitosan solution was also found to enhance the membrane permeability, moving the membrane exclusion limit to higher values. Generally, the capsules prepared tinder all tested conditions had a relatively low permeability which rarely exceeded a molecular cut-off of 40 kD based on dextran standards. Furthermore, the diffusion rate showed a strong temporal dependence, indicating that the capsules prepared under various conditions exhibit different apparent pore size densities on the surface. The results indicated that, in order to obtain the desired capsule mass-transfer properties, the preparation conditions should be carefully considered and adjusted. Adding a polyol as well as low salt amount (less than 0.15%) is preferable as a means of modulating the diffusion characteristics, without disturbing the capsule mechanical stability.

  18. Importance of calcium in modifying the acute toxicity of sodium sulphate to Hyalella azteca and Daphnia magna.

    PubMed

    Davies, Trevor D; Hall, Ken J

    2007-06-01

    Modification of the acute toxicity of sodium sulphate to Hyalella azteca and Daphnia magna was investigated using exposure water with different levels of water hardness (expressed as CaCO3 equivalents) and calcium-magnesium molar (Ca:Mg) ratios. The influence of Ca:Mg ratios on the toxicity of sodium and potassium chloride to D. magna also was investigated. For both species, the mean lethal concentrations that resulted in mortality of 50% of the sample population (LC50s), expressed as mg SO4(2-)/L, were increased significantly in harder water and in water with higher Ca:Mg ratios. The LC50s for H. azteca increased from 569 to 5259 mg/L with a change in water hardness from 25 to 250 mg/L. Furthermore, modifying the Ca:Mg ratio from 0.7 to 7.0 at a constant hardness of 100 mg/L significantly increased LC50s from 2101 to 2725 mg/L. The LC50s for D. magna were also significantly higher in harder water with LC50s increasing from 1194 to 3203 mg/L with a change in water hardness from 25 to 100 mg/L. In addition, modifying the Ca:Mg ratio from 0.7 to 7.0 significantly increased LC50s from 1194 to 1985 at a constant hardness of 25 mg/L, and from 3203 to 4395 mg/L at a constant hardness of 100 mg/L. No significant change in the toxicity of potassium or sodium chloride to D. magna was observed in waters with higher Ca:Mg ratios.

  19. Intracellular degradation of microspheres based on cross-linked dextran hydrogels or amphiphilic block copolymers: A comparative Raman microscopy study

    PubMed Central

    van Manen, Henk-Jan; van Apeldoorn, Aart A; Verrijk, Ruud; van Blitterswijk, Clemens A; Otto, Cees

    2007-01-01

    Micro- and nanospheres composed of biodegradable polymers show promise as versatile devices for the controlled delivery of biopharmaceuticals. Whereas important properties such as drug release profiles, biocompatibility, and (bio)degradability have been determined for many types of biodegradable particles, information about particle degradation inside phagocytic cells is usually lacking. Here, we report the use of confocal Raman microscopy to obtain chemical information about cross-linked dextran hydrogel microspheres and amphiphilic poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) microspheres inside RAW 264.7 macrophage phagosomes. Using quantitative Raman microspectroscopy, we show that the dextran concentration inside phagocytosed dextran microspheres decreases with cell incubation time. In contrast to dextran microspheres, we did not observe PEGT/PBT microsphere degradation after 1 week of internalization by macrophages, confirming previous studies showing that dextran microsphere degradation proceeds faster than PEGT/PBT degradation. Raman microscopy further showed the conversion of macrophages to lipid-laden foam cells upon prolonged incubation with both types of microspheres, suggesting that a cellular inflammatory response is induced by these biomaterials in cell culture. Our results exemplify the power of Raman microscopy to characterize microsphere degradation in cells and offer exciting prospects for this technique as a noninvasive, label-free optical tool in biomaterials histology and tissue engineering. PMID:17722552

  20. Self-Assembled Modified Soy Protein/Dextran Nanogel Induced by Ultrasonication as a Delivery Vehicle for Riboflavin.

    PubMed

    Jin, Bei; Zhou, Xiaosong; Li, Xiangzhong; Lin, Weiqin; Chen, Guangbin; Qiu, Riji

    2016-03-15

    A simple and green approach was developed to produce a novel nanogel via self-assembly of modified soy protein and dextran, to efficiently deliver riboflavin. First, modified soy protein was prepared by heating denaturation at 60 °C for 30 min or Alcalase hydrolysis for 40 min. Second, modified soy protein was mixed with dextran and ultrasonicated for 70 min so as to assemble nanogels. The modified soy protein-dextran nanogels were characterized by Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) and ζ-potential studies to confirm the formation of NGs. Transmission electron microscopy (TEM) revealed the NGs to be spherical with core-shell structures, in the range of 32-40 nm size. The nanogels were stable against various environmental conditions. Furthermore, the particle size of the nanogels hardly changed with the incorporation of riboflavin. The encapsulation efficiency of nanogels was found to be up to 65.9% at a riboflavin concentration of 250 μg/mL. The nanogels exhibited a faster release in simulated intestine fluid (SIF) compared with simulated gastric fluid (SGF). From the results obtained it can be concluded that modified soy protein-dextran nanogels can be considered a promising carrier for drugs and other bioactive molecule delivery purposes.

  1. Intraoperative corneal thickness measurements during corneal collagen cross-linking with isotonic riboflavin solution without dextran in corneal ectasia.

    PubMed

    Cınar, Yasin; Cingü, Abdullah Kürşat; Sahin, Alparslan; Türkcü, Fatih Mehmet; Yüksel, Harun; Caca, Ihsan

    2014-03-01

    Abstract Objective: To monitor the changes in corneal thickness during the corneal collagen cross-linking procedure by using isotonic riboflavin solution without dextran in ectatic corneal diseases. The corneal thickness measurements were obtained before epithelial removal, after epithelial removal, following the instillation of isotonic riboflavin solution without dextran for 30 min, and after 10 min of ultraviolet A irradiation. Eleven eyes of eleven patients with progressive keratoconus (n = 10) and iatrogenic corneal ectasia (n = 1) were included in this study. The mean thinnest pachymetric measurements were 391.82 ± 30.34 µm (320-434 µm) after de-epithelialization of the cornea, 435 ± 21.17 µm (402-472 µm) following 30 min instillation of isotonic riboflavin solution without dextran and 431.73 ± 20.64 µm (387-461 µm) following 10 min of ultraviolet A irradiation to the cornea. Performing corneal cross-linking procedure with isotonic riboflavin solution without dextran might not induce corneal thinning but a little swelling throughout the procedure.

  2. Levobupivacaine-dextran mixture for transversus abdominis plane block and rectus sheath block in patients undergoing laparoscopic colectomy: a randomised controlled trial.

    PubMed

    Hamada, T; Tsuchiya, M; Mizutani, K; Takahashi, R; Muguruma, K; Maeda, K; Ueda, W; Nishikawa, K

    2016-04-01

    We performed a randomised controlled double-blinded study of patients having laparoscopic colectomy with bilateral transversus abdominis plane block plus rectus sheath block, comparing a control group receiving 80 ml levobupivacaine 0.2% in saline with a dextran group receiving 80 ml levobupivacaine 0.2% in 8% low-molecular weight dextran. Twenty-seven patients were studied in each group. The mean (SD) maximum plasma concentration of levobupivacaine in the control group (1410 (322) ng.ml(-1) ) was higher than the dextran group (1141 (287) ng.ml(-1) ; p = 0.004), and was reached more quickly (50.6 (30.2) min vs 73.2 (24.6) min; p = 0.006). The area under the plasma concentration-time curve from 0 min to 240 min in the control group (229,124 (87,254) ng.min.ml(-1) ) was larger than in the dextran group (172,484 (50,502) ng.min.ml(-1) ; p = 0.007). The median (IQR [range]) of the summated numerical pain rating score at rest during the first postoperative 24 h in the control group (16 (9-20 [3-31]) was higher than in the dextran group (8 (2-11 [0-18]); p = 0.0001). In this study, adding dextran to levobupivacaine decreased the risk of levobupivacaine toxicity while providing better analgesia. © 2016 The Association of Anaesthetists of Great Britain and Ireland.

  3. Importance of the Evaluation of N-Acetyltransferase Enzyme Activity Prior to 5-Aminosalicylic Acid Medication for Ulcerative Colitis.

    PubMed

    Matthis, Andrea L; Zhang, Bin; Denson, Lee A; Yacyshyn, Bruce R; Aihara, Eitaro; Montrose, Marshall H

    2016-08-01

    5-aminosalicylic acid (5-ASA) is a classic anti-inflammatory drug for the treatment of ulcerative colitis. N-acetyltransferase (NAT) enzymes convert 5-ASA to its metabolite N-acetyl-5-ASA, and it is unresolved whether 5-ASA or N-acetyl-5-ASA is the effective therapeutic molecule. We previously demonstrated that colonic production of N-acetyl-5-ASA (NAT activity) is decreased in dextran sulfate sodium-induced colitis. Our hypothesis is that 5-ASA is the therapeutic molecule to improve colitis, with the corollary that altered NAT activity affects drug efficacy. Since varying clinical effectiveness of 5-ASA has been reported, we also ask if NAT activity varies with inflammation in pediatric or adult patients. Acute colonic inflammation was induced in C57BL/6 NAT wild-type (WT) or knockout mice, using 3.5% dextran sulfate sodium (w/v) concurrent with 5-ASA treatment. Adult and pediatric rectosigmoid biopsies were collected from control or patients with ulcerative colitis. Tissue was analyzed for NAT and myeloperoxidase activity. Dextran sulfate sodium-induced colitis was of similar severity in both NAT WT and knockout mice, and NAT activity was significantly decreased in NAT WT mice. In the setting of colitis, 5-ASA significantly restored colon length and decreased myeloperoxidase activity in NAT knockout but not in WT mice. Myeloperoxidase activity negatively correlated with NAT activity in pediatric patients, but correlation was not observed in adult patients. Inflammation decreases NAT activity in the colon of mice and human pediatric patients. Decreased NAT activity enhances the therapeutic effect of 5-ASA in mice. A NAT activity assay could be useful to help predict the efficacy of 5-ASA therapy.

  4. Parameters optimization defined by statistical analysis for cysteine-dextran radiolabeling with technetium tricarbonyl core.

    PubMed

    Núñez, Eutimio Gustavo Fernández; Faintuch, Bluma Linkowski; Teodoro, Rodrigo; Wiecek, Danielle Pereira; da Silva, Natanael Gomes; Papadopoulos, Minas; Pelecanou, Maria; Pirmettis, Ioannis; de Oliveira Filho, Renato Santos; Duatti, Adriano; Pasqualini, Roberto

    2011-04-01

    The objective of this study was the development of a statistical approach for radiolabeling optimization of cysteine-dextran conjugates with Tc-99m tricarbonyl core. This strategy has been applied to the labeling of 2-propylene-S-cysteine-dextran in the attempt to prepare a new class of tracers for sentinel lymph node detection, and can be extended to other radiopharmaceuticals for different targets. The statistical routine was based on three-level factorial design. Best labeling conditions were achieved. The specific activity reached was 5 MBq/μg. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  5. Bisphenol-A alters microbiota metabolites derived from aromatic amino acids and worsens disease activity during colitis.

    PubMed

    DeLuca, Jennifer Aa; Allred, Kimberly F; Menon, Rani; Riordan, Rebekah; Weeks, Brad R; Jayaraman, Arul; Allred, Clinton D

    2018-06-01

    Inflammatory bowel disease is a complex collection of disorders. Microbial dysbiosis as well as exposure to toxins including xenoestrogens are thought to be risk factors for inflammatory bowel disease development and relapse. Bisphenol-A has been shown to exert estrogenic activity in the colon and alter intestinal function, but the role that xenoestrogens, such as bisphenol-A , play in colonic inflammation has been previously described but with conflicting results. We investigated the ability of bisphenol-A to exacerbate colonic inflammation and alter microbiota metabolites derived from aromatic amino acids in an acute dextran sulfate sodium-induced colitis model. Female C57BL/6 mice were ovariectomized and exposed to bisphenol-A daily for 15 days. Disease activity measures include body weight, fecal consistency, and rectal bleeding. Colons were scored for inflammation, injury, and nodularity. Alterations in the levels of microbiota metabolites derived from aromatic amino acids known to reflect phenotypic changes in the gut microbiome were analyzed. Bisphenol-A exposure increased mortality and worsened disease activity as well as inflammation and nodularity scores in the middle colon region following dextran sulfate sodium exposure. Unique patterns of metabolites were associated with bisphenol-A consumption. Regardless of dextran sulfate sodium treatment, bisphenol-A reduced levels of tryptophan and several metabolites associated with decreased inflammation in the colon. This is the first study to show that bisphenol-A treatment alone can reduce microbiota metabolites derived from aromatic amino acids in the colon which may be associated with increased colonic inflammation and inflammatory bowel disease. Impact statement As rates of inflammatory bowel disease rise, discovery of the mechanisms related to the development of these conditions is important. Environmental exposure is hypothesized to play a role in etiology of the disease, as are alterations in the gut

  6. Current role of sodium bicarbonate-based preprocedural hydration for the prevention of contrast-induced acute kidney injury: a meta-analysis.

    PubMed

    Hogan, Shea E; L'Allier, Phillipe; Chetcuti, Stanley; Grossman, P Michael; Nallamothu, Brahmajee K; Duvernoy, Claire; Bates, Eric; Moscucci, Mauro; Gurm, Hitinder S

    2008-09-01

    The optimal hydration strategy for prevention of contrast-induced acute kidney injury (AKI) remains unknown. The purpose of this meta-analysis is to compare the effectiveness of normal saline (NS) versus sodium bicarbonate hydration (NaHCO(3)) for prevention of contrast-induced AKI. We performed a meta-analysis of randomized controlled trials that compared saline-based hydration with sodium bicarbonate-based hydration regimen for prophylaxis of contrast-induced AKI. The literature search included MEDLINE, EMBASE, and Cochrane databases (2000 to October 2007); conference proceedings; and bibliographies of retrieved articles. Information was extracted on study design, sample characteristics, and interventions. Random-effects models were used to calculate summary risk ratios for contrast-induced AKI, need for hemodialysis, and death. Seven trials with 1,307 subjects were included. Preprocedural hydration with sodium bicarbonate was associated with a significant decrease in the rate of contrast-induced AKI (5.96% in the NaHCO(3) arm versus 17.23% in the NS arm, summary risk ratio 0.37, 95% CI 0.18-0.714, P = .005). There was no difference in the rates of postprocedure hemodialysis or death. Formal testing revealed moderate heterogeneity and a strong likelihood of publication bias. Although sodium bicarbonate hydration was found to be superior to NS in prevention of contrast-induced AKI, these results are in the context of study heterogeneity and, likely, publication bias. An adequately powered randomized controlled trial is warranted to define the optimal hydration strategy in patients at high risk of contrast-induced AKI who are scheduled to undergo contrast administration.

  7. Absence of stearoyl-CoA desaturase-1 does not promote DSS-induced acute colitis.

    PubMed

    Macdonald, Marcia L E; Bissada, Nagat; Vallance, Bruce A; Hayden, Michael R

    2009-12-01

    Absence of stearoyl-CoA desaturase-1 (SCD1) in mice leads to chronic inflammation of the skin and increased susceptibility to atherosclerosis, while also increasing plasma inflammatory markers. A recent report suggested that SCD1 deficiency also increases disease severity in a mouse model of inflammatory bowel disease, induced by dextran sulfate sodium (DSS). However, SCD1-deficient mice are known to consume increased amounts of water, which would also be expected to increase the intake of DSS-treated water. The aim of this study was to determine the effect of SCD1 deficiency on DSS-induced acute colitis with DSS dosing adjusted to account for genotype differences in fluid consumption. Wild-type controls were treated with 3.5% DSS for 5 days to induce moderately severe colitis, while the concentration of DSS given to SCD1-deficient mice was lowered to 2.5% to control for increased fluid consumption. Colonic inflammation was assessed by clinical and histological scoring. Although SCD1-deficient mice consumed a total intake of DSS that was greater than that of wild-type controls, colonic inflammation, colon length and fecal blood were not altered by SCD1-deficiency in DSS-induced colitis, while diarrhea and total weight loss were modestly improved. Despite SCD1 deficiency leading to chronic inflammation of the skin and increased susceptibility to atherosclerosis, it does not accelerate inflammation in the DSS-induced model of acute colitis when DSS intake is controlled. These observations suggest that SCD1 deficiency does not play a significant role in colonic inflammation in this model.

  8. Prophylactic Oral Administration of Magnesium Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through a Decrease of Colonic Accumulation of P2X7 Receptor-Expressing Mast Cells.

    PubMed

    Ohbori, Kenshi; Fujiwara, Makiko; Ohishi, Akihiro; Nishida, Kentaro; Uozumi, Yoshinobu; Nagasawa, Kazuki

    2017-01-01

    The number of patients with colitis has been increasing year by year. Recently, intestinal inflammation, as one of the factors for its onset, has been demonstrated to be induced by P2X7 receptor-mediated activation of colonic immune cells such as mast cells. Activation of P2X7 receptor (P2X7R) is known to be inhibited by divalent metal cations such as magnesium, but whether or not magnesium administration prevents/relieves colitis is unknown so far. Here, we report that oral (per os (p.o.)) administration of MgCl 2 and ingestion of commercially available magnesium-rich mineral hard water relieves dextran sulfate sodium (DSS)-induced colitis in mice. Colitis was induced through ingestion of a 3% (w/v) DSS solution ad libitum for 10 d. Brilliant blue G (BBG, a P2X7R antagonist), MgCl 2 or magnesium-rich mineral hard water was administered p.o. to mice via gastric intubation once a day or ad libitum from a day before DSS administration for 11 times or 11 d, respectively. DSS-treated mice exhibited a low disease activity index, a short colon and a high histological score compared to in control mice. As BBG (250 mg/kg, p.o.), administration of a MgCl 2 solution (100 or 500 mg/kg, p.o.) and ad libitum ingestion of the magnesium-rich mineral hard water (212 ppm as magnesium) partially, but significantly, attenuated the severity of colitis by decreasing the accumulation of P2X7R-immunopositive mast cells in the colon. Therefore, prophylactic p.o. administration/ingestion of magnesium is considered to be partially effective to protect mice against DSS-induced colitis by inhibiting P2X7R-mediated activation/accumulation of colonic mast cells.

  9. Synthesis of silver nanoparticles in the presence of diethylaminoethyl-dextran hydrochloride polymer and their SERS activity

    NASA Astrophysics Data System (ADS)

    Mikac, L.; Jurkin, T.; Štefanić, G.; Ivanda, Mile; Gotić, Marijan

    2017-09-01

    The silver nanoparticles (AgNPs) were synthesized upon γ-irradiation of AgNO3 precursor suspensions in the presence of diethylaminoethyl-dextran hydrochloride (DEAE-dextran) cationic polymer as a stabilizer. The dose rate of γ-irradiation was 32 kGy h-1, and absorbed doses were 30 and 60 kGy. The γ-irradiation of the precursor suspension at acidic or neutral pH conditions produced predominantly the silver(I) chloride (AgCl) particles, because of the poor solubility of AgCl already present in the precursor suspension. The origin of AgCl in the precursor suspension was due to the presence of chloride ions in DEAE-dextran hydrochloride polymer. The addition of ammonia to the precursor suspension dissolved the AgCl precipitate, and the γ-irradiation of such colourless suspension at alkali pH produced a stable aqueous suspension with rather uniform spherical AgNPs of approximately 30 nm in size. The size of AgNPs was controlled by varying the AgNO3/DEAE-dextran concentration in the suspensions. The surface-enhanced Raman scattering (SERS) activities of synthesized AgNPs were examined using organic molecules rhodamine 6G, pyridine and 4-mercaptobenzoic acid (4-MBA). The NaBH4 was used as SERS aggregation agent. The SERS results have shown that in the presence of synthesized AgNPs, it was possible to detect low concentration of tested compounds.

  10. Highly Selective Photothermal Therapy by a Phenoxylated-Dextran-Functionalized Smart Carbon Nanotube Platform.

    PubMed

    Han, Seungmin; Kwon, Taeyun; Um, Jo-Eun; Haam, Seungjoo; Kim, Woo-Jae

    2016-05-01

    Near-infrared (NIR) photothermal therapy using biocompatible single-walled carbon nanotubes (SWNTs) is advantageous because as-produced SWNTs, without additional size control, both efficiently absorb NIR light and demonstrate high photothermal conversion efficiency. In addition, covalent attachment of receptor molecules to SWNTs can be used to specifically target infected cells. However, this technique interrupts SWNT optical properties and inevitably lowers photothermal conversion efficiency and thus remains major hurdle for SWNT applications. This paper presents a smart-targeting photothermal therapy platform for inflammatory disease using newly developed phenoxylated-dextran-functionalized SWNTs. Phenoxylated dextran is biocompatible and efficiently suspends SWNTs by noncovalent π-π stacking, thereby minimizing SWNT bundle formations and maintaining original SWNT optical properties. Furthermore, it selectively targets inflammatory macrophages by scavenger-receptor binding without any additional receptor molecules; therefore, its preparation is a simple one-step process. Herein, it is experimentally demonstrated that phenoxylated dextran-SWNTs (pD-SWNTs) are also biocompatible, selectively penetrate inflammatory macrophages over normal cells, and exhibit high photothermal conversion efficiency. Consequently, NIR laser-triggered macrophage treatment can be achieved with high accuracy by pD-SWNT without damaging receptor-free cells. These smart targeting materials can be a novel photothermal agent candidate for inflammatory disease. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Toxicity, toxicokinetics and biodistribution of dextran stabilized Iron oxide Nanoparticles for biomedical applications.

    PubMed

    Remya, N S; Syama, S; Sabareeswaran, A; Mohanan, P V

    2016-09-10

    Advancement in the field of nanoscience and technology has alarmingly raised the call for comprehending the potential health effects caused by deliberate or unintentional exposure to nanoparticles. Iron oxide magnetic nanoparticles have an increasing number of biomedical applications and hence a complete toxicological profile of the nanomaterial is therefore a mandatory requirement prior to its intended usage to ensure safety and to minimize potential health hazards upon its exposure. The present study elucidates the toxicity of in house synthesized Dextran stabilized iron oxide nanoparticles (DINP) in a regulatory perspective through various routes of exposure, its associated molecular, immune, genotoxic, carcinogenic effects and bio distribution profile. Synthesized ferrite nanomaterials were successfully coated with dextran (<25nm) and were physicochemically characterized and subjected to in vitro and in vivo toxicity evaluations. The results suggest that surface coating of ferrite nanoparticles with dextran helps in improvising particle stability in biological environments. The nanoparticles do not seem to induce oxidative stress mediated toxicological effects, nor altered physiological process or behavior changes or visible pathological lesions. Furthermore no anticipated health hazards are likely to be associated with the use of DINP and could be concluded that the synthesized DINP is nontoxic/safe to be used for biomedical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Attenuation of acute plasma cortisol response in calves following intravenous sodium salicylate administration prior to castration.

    PubMed

    Coetzee, J F; Gehring, R; Bettenhausen, A C; Lubbers, B V; Toerber, S E; Thomson, D U; Kukanich, B; Apley, M D

    2007-08-01

    Pain associated with castration in cattle is an animal welfare concern in beef production. This study examined the effect of oral aspirin and intravenous (i.v.) sodium salicylate on acute plasma cortisol response following surgical castration. Twenty bulls, randomly assigned to the following groups, (i) uncastrated, untreated controls, (ii) castrated, untreated controls, (iii) 50 mg/kg sodium salicylate i.v. precastration and (iv) 50 mg/kg aspirin (acetylsalicylic acid) per os precastration, were blood sampled at 3, 10, 20, 30, 40, 50 min and 1, 1.5, 2, 4, 6, 8, 10 and 12 h postcastration. Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. Data were analyzed using noncompartmental analysis, a simple cosine model, anova and t-tests. Intravenous salicylate V(d(ss)) was 0.18 L/kg, Cl(B) was 3.36 mL/min/kg and t(1/2 lambda) was 0.63 h. Plasma salicylate concentrations above 25 microg/mL coincided with significant attenuation in peak cortisol concentrations (P = 0.029). Peak salicylate concentrations following oral aspirin administration was <10 microg/mL and failed to attenuate cortisol response. Once salicylate concentrations decreased below 5 microg/mL, cortisol response in the castrated groups was significantly higher than uncastrated controls (P = 0.018). These findings have implications for designing drug regimens to provide analgesia during routine animal husbandry procedures.

  13. Effect of Au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations.

    PubMed

    Medhat, Dalia; Hussein, Jihan; El-Naggar, Mehrez E; Attia, Mohamed F; Anwar, Mona; Latif, Yasmine Abdel; Booles, Hoda F; Morsy, Safaa; Farrag, Abdel Razik; Khalil, Wagdy K B; El-Khayat, Zakaria

    2017-07-01

    Dextran-capped gold nanoparticles (Au-dextran NPs) were prepared exploiting the natural polysaccharide polymer as both reducing and stabilizing agent in the synthesis process, aiming at studying their antitumor effect on solid carcinoma and EAC-bearing mice. To this end, Au-dextran NPs were designed via simple eco-friendly chemical reaction and they were characterized revealing the monodispersed particles with narrow distributed size of around 49nm with high negative charge. In vivo experiments were performed on mice. Biochemical analysis of liver and kidney functions and oxidation stress ratio in addition to histopathological investigations of such tumor tissues were done demonstrating the potentiality of Au-dextran NPs as antitumor agent. The obtained results revealed that EAC and solid tumors caused significant increase in liver and kidney functions, liver oxidant parameters, alpha feto protein levels and diminished liver antioxidant accompanied by positive expression of tumor protein p53 of liver while the treatment with Au-dextran NPs for both types caused improvement in liver and kidney functions, increased liver antioxidant, increased the expression level of B-cell lymphoma 2 gene and subsequently suppressed the apoptotic pathway. As a result, the obtained data provides significant antitumor effects of the Au-dextran NPs in both Ehrlich ascites and solid tumor in mice models. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Changes in the Expression and Distribution of Claudins, Increased Epithelial Apoptosis, and a Mannan-Binding Lectin-Associated Immune Response Lead to Barrier Dysfunction in Dextran Sodium Sulfate-Induced Rat Colitis

    PubMed Central

    Yuan, Bosi; Zhou, Shuping; Lu, Youke; Liu, Jiong; Jin, Xinxin; Wan, Haijun; Wang, Fangyu

    2015-01-01

    Background/Aims This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. Methods Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. Results The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%±1.2% in controls and was significantly increased to 7.2%±1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. Conclusions There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability. PMID:25717051

  15. Changes in the Expression and Distribution of Claudins, Increased Epithelial Apoptosis, and a Mannan-Binding Lectin-Associated Immune Response Lead to Barrier Dysfunction in Dextran Sodium Sulfate-Induced Rat Colitis.

    PubMed

    Yuan, Bosi; Zhou, Shuping; Lu, Youke; Liu, Jiong; Jin, Xinxin; Wan, Haijun; Wang, Fangyu

    2015-11-23

    This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%±1.2% in controls and was significantly increased to 7.2%±1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability.

  16. Resveratrol (Trans-3,5,4′-trihydroxystilbene) Induces Silent Mating Type Information Regulation-1 and Down-Regulates Nuclear Transcription Factor-κB Activation to Abrogate Dextran Sulfate Sodium-Induced Colitis

    PubMed Central

    Singh, Udai P.; Singh, Narendra P.; Singh, Balwan; Hofseth, Lorne J.; Price, Robert L.; Nagarkatti, Mitzi

    2010-01-01

    Inflammatory bowel disease is a chronic, relapsing, and tissue-destructive disease. Resveratrol (3,4,5-trihydroxy-trans-stilbene), a naturally occurring polyphenol that exhibits beneficial pleiotropic health effects, is recognized as one of the most promising natural molecules in the prevention and treatment of chronic inflammatory disease and autoimmune disorders. In the present study, we investigated the effect of resveratrol on dextran sodium sulfate (DSS)-induced colitis in mice and found that it effectively attenuated overall clinical scores as well as various pathological markers of colitis. Resveratrol reversed the colitis-associated decrease in body weight and increased levels of serum amyloid A, tumor necrosis factor-α, interleukin (IL-6), and IL-1β. After resveratrol treatment, the percentage of CD4+ T cells in mesenteric lymph nodes (MLN) of colitis mice was restored to normal levels, and there was a decrease in these cells in the colon lamina propria (LP). Likewise, the percentages of macrophages in MLN and the LP of mice with colitis were decreased after resveratrol treatment. Resveratrol also suppressed cyclooxygenase-2 (COX-2) expression induced in DSS-exposed mice. Colitis was associated with a decrease in silent mating type information regulation-1 (SIRT1) gene expression and an increase in p-inhibitory κB expression and nuclear transcription factor-κB (NF-κB) activation. Resveratrol treatment of mice with colitis significantly reversed these changes. This study demonstrates for the first time that SIRT1 is involved in colitis, functioning as an inverse regulator of NF-κB activation and inflammation. Furthermore, our results indicate that resveratrol may protect against colitis through up-regulation of SIRT1 in immune cells in the colon. PMID:19940103

  17. 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

  18. Aldosterone acutely stimulates NCC activity via a SPAK-mediated pathway.

    PubMed

    Ko, Benjamin; Mistry, Abinash C; Hanson, Lauren; Mallick, Rickta; Wynne, Brandi M; Thai, Tiffany L; Bailey, James L; Klein, Janet D; Hoover, Robert S

    2013-09-01

    Hypertension is a leading cause of morbidity and mortality worldwide, and disordered sodium balance has long been implicated in its pathogenesis. Aldosterone is perhaps the key regulator of sodium balance and thus blood pressure. The sodium chloride cotransporter (NCC) in the distal convoluted tubule of the kidney is a major site of sodium reabsorption and plays a key role in blood pressure regulation. Chronic exposure to aldosterone increases NCC protein expression and function. However, more acute effects of aldosterone on NCC are unknown. In our salt-abundant modern society where chronic salt deprivation is rare, understanding the acute effects of aldosterone is critical. Here, we examined the acute effects (12-36 h) of aldosterone on NCC in the rodent kidney and in a mouse distal convoluted tubule cell line. Studies demonstrated that aldosterone acutely stimulated NCC activity and phosphorylation without affecting total NCC abundance or surface expression. This effect was dependent upon the presence of the mineralocorticoid receptor and serum- and glucocorticoid-regulated kinase 1 (SGK1). Furthermore, STE20/SPS-1-related proline/alanine-rich kinase (SPAK) phosphorylation also increased, and gene silencing of SPAK eliminated the effect of aldosterone on NCC activity. Aldosterone administration via a minipump in adrenalectomized rodents confirmed an increase in NCC phosphorylation without a change in NCC total protein. These data indicate that acute aldosterone-induced SPAK-dependent phosphorylation of NCC increases individual transporter activity.

  19. A role for sodium-chloride cotransporters in the rapid regulation of ion uptake following acute environmental acidosis: new insights from the zebrafish model

    PubMed Central

    Perry, Steve F.

    2016-01-01

    The effects of acute exposure to acidic water on Na+ and Cl− homeostasis, and the mechanisms underlying their compensatory regulation, were investigated in the larval zebrafish Danio rerio. Exposure to acidic water (pH 4.0; control pH 7.6) for 2 h significantly reduced Na+ uptake and whole body Na+ content. Nevertheless, the capacity for Na+ uptake was substantially increased in fish preexposed to acidic water but measured in control water. Based on the accumulation of the Na+-selective dye, Sodium Green, two ionocyte subtypes exhibited intracellular Na+ enrichment after preexposure to acidic water: H+-ATPase rich (HR) cells, which coexpress the Na+/H+ exchanger isoform 3b (NHE3b), and a non-HR cell population. In fish experiencing Na+-Cl− cotransporter (NCC) knockdown, we observed no Sodium Green accumulation in the latter cell type, suggesting the non-HR cells were NCC cells. Elimination of NHE3b-expressing HR cells did not prevent the increased Na+ uptake following acid exposure. On the other hand, the increased Na+ uptake was abolished when the acidic water was enriched with Na+ and Cl−, but not with Na+ only, indicating that the elevated Na+ uptake after acid exposure was associated with the compensatory regulation of Cl−. Further examinations demonstrated that acute acid exposure also reduced whole body Cl− levels and increased the capacity for Cl− uptake. Moreover, knockdown of NCC prevented the increased uptake of both Na+ and Cl− after exposure to acidic water. Together, the results of the present study revealed a novel role of NCC in the compensatory regulation of Na+ and Cl− uptake following acute acidosis. PMID:27784676

  20. 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

  1. Intravenous administration of hypertonic sodium chloride solution with dextran or isotonic sodium chloride solution for treatment of septic shock secondary to pyometra in dogs.

    PubMed

    Fantoni, D T; Auler Junior, J O; Futema, F; Cortopassi, S R; Migliati, E R; Faustino, M; de Oliveira, C M

    1999-11-01

    To determine effects of i.v. administration of hypertonic saline (7.5% NaCl) solution with 6% dextran 70 (HSSD) or isotonic saline (0.9% NaCl) solution (ISS) to dogs with septic shock secondary to pyometra. Prospective, randomized, clinical study. 14 client-owned dogs with septic shock secondary to pyometra. Prior to emergency ovariohysterectomy, catheters were placed in pulmonary and femoral arteries of each dog to evaluate hemodynamic and oxygenation status. Immediately prior to surgery, 7 dogs received HSSD (4 ml/kg [1.82 ml/lb] of body weight, i.v.) and 7 dogs received ISS (32 ml/kg [14.54 ml/lb], i.v.) during a 5-minute period. Measurements of hemodynamic and oxygenation variables were obtained before and 5 and 20 minutes after administration of fluids. Mean arterial pressure (MAP) increased significantly 5 and 20 minutes after administration of HSSD, whereas ISS did not affect MAP. However, cardiac output, cardiac index, and oxygen delivery increased and hematocrit decreased after both treatments. Oxygen consumption and extraction rate and degree of acidosis did not improve after either treatment. Intravenous administration of small volumes of HSSD to dogs with septic shock secondary to pyometra resulted in improvement of hemodynamic and oxygenation status. Although cardiac output, cardiac index, and oxygen delivery improved after administration of a volume of ISS equal to 8 times that of HSSD, MAP increased to > 80 mm Hg only after treatment with HSSD. Administration of HSSD may be an effective treatment for septic shock in dogs.

  2. Pentadecapeptide BPC 157 and anaphylactoid reaction in rats and mice after intravenous dextran and white egg administration.

    PubMed

    Duplancic, Bozidar; Stambolija, Vasilije; Holjevac, Jadranka; Zemba, Mladen; Balenovic, Igor; Drmic, Domagoj; Suran, Jelena; Radic, Bozo; Filipovic, Marinko; Blagaic, Alenka Boban; Brcic, Luka; Kolenc, Danijela; Grabarevic, Zeljko; Seiwerth, Sven; Sikiric, Predrag

    2014-03-15

    Anesthetized mice or rats received intravenously 6%, 10%, 20%, 40%, 60%, 80%, and 90% dextran and/or white egg (1ml/rat or 0.15ml/mouse) into their tails. Medication (/kg b.w., 5ml/kg) was given intraperitoneally (BPC 157 10µg, 1µg, 10ng, and 10pg/kg, chloropyramine 20mg/kg, and cimetidine 10mg/kg intraperitoneally, alone or in combination while controls received an equivolume of saline), immediately after challenge or, alternatively, at 5min after or 24 or 48h before challenge. The effect was assessed at 5, 10, 20 and 30min after dextran and/or white egg challenge. We commonly noted prominent edema involving the face, upper and lower lip, snout, paws and scrotum (presented with extreme cyanosis), poor respiration and the number of fatalities after dextran and/or white egg application. Contrary, BPC 157 regimens (10µg, 1µg, 10ng, and 10pg/kg) effectively, may both prevent anaphylactoid reactions that may arise from dextran and/or white egg application and furthermore, rescue already advanced reactions when given after the challenge. Chloropyramine and cimetidine given alone were only moderately effective. When given together with BPC 157, the observed effect correlates with the strong effect of BPC 157 given alone. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Pilot study of combination transcriptional modulation therapy with sodium phenylbutyrate and 5-azacytidine in patients with acute myeloid leukemia or myelodysplastic syndrome.

    PubMed

    Maslak, P; Chanel, S; Camacho, L H; Soignet, S; Pandolfi, P P; Guernah, I; Warrell, R; Nimer, S

    2006-02-01

    Epigenetic mechanisms underlying tumorigenesis have recently received much attention as potential therapeutic targets of human cancer. We designed a pilot study to target DNA methylation and histone deacetylation through the sequential administration of 5-azacytidine followed by sodium phenylbutyrate (PB) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Ten evaluable patients (eight AML, two MDS) were treated with seven consecutive daily subcutaneous injections of 5-azacytidine at 75 mg/m2 followed by 5 days of sodium PB given intravenously at a dose of 200 mg/kg. Five patients (50%) were able to achieve a beneficial clinical response (partial remission or stable disease). One patient with MDS proceeded to allogeneic stem cell transplantation and is alive without evidence of disease 39 months later. The combination regimen was well tolerated with common toxicities of injection site skin reaction (90% of the patients) from 5-azacytidine, and somnolence/fatigue from the sodium PB infusion (80% of the patients). Correlative laboratory studies demonstrated the consistent reacetylation of histone H4, although no relationship with the clinical response could be demonstrated. Results from this pilot study demonstrate that a combination approach targeting different mechanisms of transcriptional modulation is clinically feasible with acceptable toxicity and measurable biologic and clinical outcomes.

  4. Optimal size for heating efficiency of superparamagnetic dextran-coated magnetite nanoparticles for application in magnetic fluid hyperthermia

    NASA Astrophysics Data System (ADS)

    Shaterabadi, Zhila; Nabiyouni, Gholamreza; Soleymani, Meysam

    2018-06-01

    Dextran-coated magnetite (Fe3O4) nanoparticles with average particle sizes of 4 and 19 nm were synthesized through in situ and semi-two-step co-precipitation methods, respectively. The experimental results confirm the formation of pure phase of magnetite as well as the presence of dextran layer on the surface of modified magnetite nanoparticles. The results also reveal that both samples have the superparamagnetic behavior. Furthermore, calorimetric measurements show that the dextran-coated Fe3O4 nanoparticles with an average size of 4 nm cannot produce any appreciable heat under a biologically safe alternating magnetic field used in hyperthermia therapy; whereas, the larger ones (average size of 19 nm) are able to increase the temperature of their surrounding medium up to above therapeutic range. In addition, measured specific absorption rate (SAR) values confirm that magnetite nanoparticles with an average size of 19 nm are very excellent candidates for application in magnetic hyperthermia therapy.

  5. Aldosterone acutely stimulates NCC activity via a SPAK-mediated pathway

    PubMed Central

    Mistry, Abinash C.; Hanson, Lauren; Mallick, Rickta; Wynne, Brandi M.; Thai, Tiffany L.; Bailey, James L.; Klein, Janet D.; Hoover, Robert S.

    2013-01-01

    Hypertension is a leading cause of morbidity and mortality worldwide, and disordered sodium balance has long been implicated in its pathogenesis. Aldosterone is perhaps the key regulator of sodium balance and thus blood pressure. The sodium chloride cotransporter (NCC) in the distal convoluted tubule of the kidney is a major site of sodium reabsorption and plays a key role in blood pressure regulation. Chronic exposure to aldosterone increases NCC protein expression and function. However, more acute effects of aldosterone on NCC are unknown. In our salt-abundant modern society where chronic salt deprivation is rare, understanding the acute effects of aldosterone is critical. Here, we examined the acute effects (12–36 h) of aldosterone on NCC in the rodent kidney and in a mouse distal convoluted tubule cell line. Studies demonstrated that aldosterone acutely stimulated NCC activity and phosphorylation without affecting total NCC abundance or surface expression. This effect was dependent upon the presence of the mineralocorticoid receptor and serum- and glucocorticoid-regulated kinase 1 (SGK1). Furthermore, STE20/SPS-1-related proline/alanine-rich kinase (SPAK) phosphorylation also increased, and gene silencing of SPAK eliminated the effect of aldosterone on NCC activity. Aldosterone administration via a minipump in adrenalectomized rodents confirmed an increase in NCC phosphorylation without a change in NCC total protein. These data indicate that acute aldosterone-induced SPAK-dependent phosphorylation of NCC increases individual transporter activity. PMID:23739593

  6. New shell crosslinked micelles from dextran with hydrophobic end groups and their interaction with bioactive molecules.

    PubMed

    Mocanu, Georgeta; Nichifor, Marieta; Stanciu, Magdalena C

    2015-03-30

    Micelles formed in aqueous solution by dextran with hydrophobic (alkyl) end-groups were stabilized through divinyl sulfone crosslinking of the dextran shell. The efficacy of the crosslinking reaction was influenced by the divinyl sulfone amount, the pH and micelle concentration. Crosslinked micelles with a moderate crosslinking degree were further functionalized by attachment of 10 and 17 moles% N-(2-hydroxypropyl)-N,N-dimethyl-N-benzylammonium chloride groups along the dextran chain. The size and shape of both crosslinked micelles and their cationic derivatives were analyzed by DLS and TEM. The prepared micelles were able to bind anionic diclofenac (60-370 mg/g), hydrophobic anionic indometacin (70-120 mg/g), and hydrophobic alpha-tocopherol (170-220 mg/g) or ergocalciferol (90-110 mg/g) by hydrophobic or/and electrostatic forces. The release experiments and the antioxidant activity of bound alpha-tocopherol highlighted the potential of the new nano-sized micelles mainly as carriers for prolonged and controlled delivery of hydrophobic drugs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Development of acute pancreatitis caused by sodium valproate in a patient with bipolar disorder on hemodialysis for chronic renal failure: a case report.

    PubMed

    Okayasu, Hiroaki; Shinozaki, Takahiro; Osone, Akira; Ozeki, Yuji; Shimoda, Kazutaka

    2014-03-29

    Cases of acute pancreatitis caused by sodium valproate (VPA) have been reported by many authors thus far. However, most of these were cases with epilepsy. Chronic renal failure is also regarded as a risk factor for acute pancreatitis. Here, we report a case of acute pancreatitis development due to VPA in a patient with bipolar disorder on hemodialysis for chronic renal failure. The patient was a 52-year-old Japanese male who was diagnosed as bipolar disorder on hemodialysis for renal failure. He was treated with VPA and manic symptoms gradually stabilized. However, the patient complained of severe abdominal pain. Blood amylase was found to be markedly high, and computed tomography revealed pancreatomegaly and an increased amount of peripancreatic fat. Hence, we diagnosed the case as acute pancreatitis caused by VPA. We discontinued oral medication, and he was started on a pancreatic enzyme inhibitor, antibiotics, and transfusion, and he showed improvement. It has been reported that acute pancreatitis induced by VPA is caused by intermediate metabolites of VPA. We consider that patients with renal failure are prone to pancreatitis caused by VPA because of the accumulation of these intermediate metabolites. We need close monitoring for serious adverse effects such as pancreatitis when we prescribe VPA to patients with bipolar disorder on hemodialysis for chronic renal failure, although VPA is safer than other mood stabilizers.

  8. Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis

    PubMed Central

    Adeva-Andany, María M.; Fernández-Fernández, Carlos; Mouriño-Bayolo, David; Castro-Quintela, Elvira; Domínguez-Montero, Alberto

    2014-01-01

    Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial regarding clinical outcomes or mortality rate. Patients with advanced chronic kidney disease usually show metabolic acidosis due to increased unmeasured anions and hyperchloremia. It has been suggested that metabolic acidosis might have a negative impact on progression of kidney dysfunction and that sodium bicarbonate administration might attenuate this effect, but further evaluation is required to validate such a renoprotective strategy. Sodium bicarbonate is the predominant buffer used in dialysis fluids and patients on maintenance dialysis are subjected to a load of sodium bicarbonate during the sessions, suffering a transient metabolic alkalosis of variable severity. Side effects associated with sodium bicarbonate therapy include hypercapnia, hypokalemia, ionized hypocalcemia, and QTc interval prolongation. The potential impact of regular sodium bicarbonate therapy on worsening vascular calcifications in patients with chronic kidney disease has been insufficiently investigated. PMID:25405229

  9. Final report on the safety assessment of sodium sulfite, potassium sulfite, ammonium sulfite, sodium bisulfite, ammonium bisulfite, sodium metabisulfite and potassium metabisulfite.

    PubMed

    Nair, Bindu; Elmore, Amy R

    2003-01-01

    Sodium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Potassium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are inorganic salts that function as reducing agents in cosmetic formulations. All except Sodium Metabisulfite also function as hair-waving/straightening agents. In addition, Sodium Sulfite, Potassium Sulfite, Sodium Bisulfite, and Sodium Metabisulfite function as antioxidants. Although Ammonium Sulfite is not in current use, the others are widely used in hair care products. Sulfites that enter mammals via ingestion, inhalation, or injection are metabolized by sulfite oxidase to sulfate. In oral-dose animal toxicity studies, hyperplastic changes in the gastric mucosa were the most common findings at high doses. Ammonium Sulfite aerosol had an acute LC(50) of >400 mg/m(3) in guinea pigs. A single exposure to low concentrations of a Sodium Sulfite fine aerosol produced dose-related changes in the lung capacity parameters of guinea pigs. A 3-day exposure of rats to a Sodium Sulfite fine aerosol produced mild pulmonary edema and irritation of the tracheal epithelium. Severe epithelial changes were observed in dogs exposed for 290 days to 1 mg/m(3) of a Sodium Metabisulfite fine aerosol. These fine aerosols contained fine respirable particle sizes that are not found in cosmetic aerosols or pump sprays. None of the cosmetic product types, however, in which these ingredients are used are aerosolized. Sodium Bisulfite (tested at 38%) and Sodium Metabisulfite (undiluted) were not irritants to rabbits following occlusive exposures. Sodium Metabisulfite (tested at 50%) was irritating to guinea pigs following repeated exposure. In rats, Sodium Sulfite heptahydrate at large doses (up to 3.3 g/kg) produced fetal toxicity but not teratogenicity. Sodium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite were not teratogenic for mice, rats, hamsters, or rabbits at doses up to 160 mg/kg. Generally, Sodium Sulfite, Sodium

  10. Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction: An Analysis From the High-Risk Myocardial Infarction Database Initiative.

    PubMed

    Ferreira, João Pedro; Girerd, Nicolas; Duarte, Kevin; Coiro, Stefano; McMurray, John J V; Dargie, Henry J; Pitt, Bertram; Dickstein, Kenneth; Testani, Jeffrey M; Zannad, Faiez; Rossignol, Patrick

    2017-02-01

    Serum chloride levels were recently found to be independently associated with mortality in heart failure (HF). We investigated the relationship between serum chloride and clinical outcomes in 7195 subjects with acute myocardial infarction complicated by reduced left ventricular function and HF. The studied outcomes were all-cause mortality, cardiovascular mortality, and hospitalization for HF. Both chloride and sodium had a nonlinear association with the studied outcomes (P<0.05 for linearity). Patients in the lowest chloride tertile (chloride ≤100) were older, had more comorbidities, and had lower sodium levels (P<0.05 for all). Serum chloride showed a significant interaction with sodium with regard to all studied outcomes (P for interaction <0.05 for all). The lowest chloride tertile (≤100 mmol/L) was associated with increased mortality rates in the context of lower sodium (≤138 mmol/L; adjusted hazard ratio [95% confidence interval] for all-cause mortality=1.42 (1.14-1.77); P=0.002), whereas in the context of higher sodium levels (>141 mmol/L), the association with mortality was lost. Spline-transformed chloride and its interaction with sodium did not add significant prognostic information on top of other well-established prognostic variables (P>0.05 for all outcomes). In post-myocardial infarction with systolic dysfunction and HF, low serum chloride was associated with mortality (but not hospitalization for HF) in the setting of lower sodium. Overall, chloride and its interaction with sodium did not add clinically relevant prognostic information on top of other well-established prognostic variables. Taken together, these data support an integrated and critical consideration of chloride and sodium interplay. © 2017 American Heart Association, Inc.

  11. Hourly oral sodium chloride for the rapid and predictable treatment of hyponatremia.

    PubMed

    Kerns, Eric; Patel, Shweta; Cohen, David M

    2014-12-01

    Hypertonic NaCl is first-line therapy for acute, severe and symptomatic hyponatremia; however, its use is often restricted to the intensive care unit (ICU). A 35-year-old female inpatient with an optic chiasm glioma and ventriculoperitoneal shunt for hydrocephalus developed acute hyponatremia (sodium 122 mEq/l) perhaps coinciding with haloperidol treatment. The sum of her urinary sodium and potassium concentrations was markedly hypertonic vis-à-vis plasma; it was inferred that serum sodium concentration would continue to fall even in the complete absence of fluid intake. Intravenous (i.v.) 3% NaCl was recommended; however, a city-wide public health emergency precluded her transfer to the ICU. She was treated with hourly oral NaCl tablets in a dose calculated to deliver the equivalent of 0.5 ml/kg/h of 3% NaCl with an objective of increasing the serum sodium concentration by 6 mEq/l. She experienced a graded and predictable increase in serum sodium concentration. A slight overshoot to 129 mEq/l was rapidly corrected with 0.25 l of D5W, and she stabilized at 127 mEq/l. We conclude that hourly oral NaCl, in conjunction with careful monitoring of the serum sodium concentration, may provide an attractive alternative to i.v. 3% NaCl for selected patients with severe hyponatremia.

  12. Unusual Voltage-Gated Sodium Currents as Targets for Pain.

    PubMed

    Barbosa, C; Cummins, T R

    2016-01-01

    Pain is a serious health problem that impacts the lives of many individuals. Hyperexcitability of peripheral sensory neurons contributes to both acute and chronic pain syndromes. Because voltage-gated sodium currents are crucial to the transmission of electrical signals in peripheral sensory neurons, the channels that underlie these currents are attractive targets for pain therapeutics. Sodium currents and channels in peripheral sensory neurons are complex. Multiple-channel isoforms contribute to the macroscopic currents in nociceptive sensory neurons. These different isoforms exhibit substantial variations in their kinetics and pharmacology. Furthermore, sodium current complexity is enhanced by an array of interacting proteins that can substantially modify the properties of voltage-gated sodium channels. Resurgent sodium currents, atypical currents that can enhance recovery from inactivation and neuronal firing, are increasingly being recognized as playing potentially important roles in sensory neuron hyperexcitability and pain sensations. Here we discuss unusual sodium channels and currents that have been identified in nociceptive sensory neurons, describe what is known about the molecular determinants of the complex sodium currents in these neurons. Finally, we provide an overview of therapeutic strategies to target voltage-gated sodium currents in nociceptive neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Pathogenesis of Infection by Clinical and Environmental Strains of Vibrio vulnificus in Iron-Dextran-Treated Mice

    PubMed Central

    Starks, Angela M.; Schoeb, Trenton R.; Tamplin, Mark L.; Parveen, Salina; Doyle, Thomas J.; Bomeisl, Philip E.; Escudero, Gloria M.; Gulig, Paul A.

    2000-01-01

    Vibrio vulnificus is an opportunistic pathogen that contaminates oysters harvested from the Gulf of Mexico. In humans with compromising conditions, especially excess levels of iron in plasma and tissues, consumption of contaminated seafood or exposure of wounds to contaminated water can lead to systemic infection and disfiguring skin infection with extremely high mortality. V. vulnificus-associated diseases are noted for the rapid replication of the bacteria in host tissues, with extensive tissue damage. In this study we examined the virulence attributes of three virulent clinical strains and three attenuated oyster or seawater isolates in mouse models of systemic disease. All six V. vulnificus strains caused identical skin lesions in subcutaneously (s.c.) inoculated iron dextran-treated mice in terms of numbers of recovered CFU and histopathology; however, the inocula required for identical frequency and magnitude of infection were at least 350-fold higher for the environmental strains. At lethal doses, all strains caused s.c. skin lesions with extensive edema, necrosis of proximate host cells, vasodilation, and as many as 108 CFU/g, especially in perivascular regions. These data suggest that the differences between these clinical and environmental strains may be related to growth in the host or susceptibility to host defenses. In non-iron dextran-treated mice, strains required 105-fold-higher inocula to cause an identical disease process as with iron dextran treatment. These results demonstrate that s.c. inoculation of iron dextran-treated mice is a useful model for studying systemic disease caused by V. vulnificus. PMID:10992486

  14. Gradient-dependent release of the model drug TRITC-dextran from FITC-labeled BSA hydrogel nanocarriers in the hair follicles of porcine ear skin.

    PubMed

    Tran, Ngo Bich Nga Nathalie; Knorr, Fanny; Mak, Wing Cheung; Cheung, Kwan Yee; Richter, Heike; Meinke, Martina; Lademann, Jürgen; Patzelt, Alexa

    2017-07-01

    Hair follicle research is currently focused on the development of drug-loaded nanocarriers for the targeting of follicular structures in the treatment of skin and hair follicle-related disorders. In the present study, a dual-label nanocarrier system was implemented in which FITC-labeled BSA hydrogel nanocarriers loaded with the model drug and dye TRITC-dextran were applied topically to porcine ear skin. Follicular penetration and the distribution of both dyes corresponding to the nanocarriers and the model drug in the follicular ducts subsequent to administration to the skin were investigated using confocal laser scanning microscopy. The release of TRITC-dextran from the particles was induced by washing of the nanocarriers, which were kept in a buffer containing TRITC-labeled dextran to balance out the diffusion of the dextran during storage, thereby changing the concentration gradient. The results showed a slightly but statistically significantly deeper follicular penetration of fluorescent signals corresponding to TRITC-dextran as opposed to fluorescence corresponding to the FITC-labeled particles. The different localizations of the dyes in the cross-sections of the skin samples evidenced the release of the model drug from the labeled nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Dextran derivative-based pH-sensitive liposomes for cancer immunotherapy.

    PubMed

    Yuba, Eiji; Tajima, Naoki; Yoshizaki, Yuta; Harada, Atsushi; Hayashi, Hiroshi; Kono, Kenji

    2014-03-01

    pH-Sensitive dextran derivatives having 3-methylglutarylated residues (MGlu-Dex) were prepared by reacting dextran with 3-methyl-glutaric anhydride. MGlu-Dex changed the protonation state and their characteristics from hydrophilic to hydrophobic in neutral and acidic pH regions. Surface modification of egg yolk phosphatidylcholine liposomes with MGlu-Dex produced highly pH-sensitive liposomes that were stable at neutral pH but which were destabilized strongly in the weakly acidic pH region. MGlu-Dex-modified liposomes were taken up efficiently by dendritic cells and delivered entrapped ovalbumin (OVA) molecules into the cytosol. When MGlu-Dex-modified liposomes loaded with OVA were administered subcutaneously to mice, the antigen-specific humoral and cellular immunity was induced more effectively than the unmodified liposomes loaded with OVA. Furthermore, administration of MGlu-Dex-modified liposomes loaded with OVA to mice bearing E.G7-OVA tumor significantly suppressed tumor growth and extended the mice survival. Results suggest that MGlu-Dex-modified liposomes are promising for the production of safe and potent antigen delivery systems that contribute to the establishment of efficient cancer immunotherapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Increased Late Sodium Current Contributes to the Electrophysiological Effects of Chronic, but Not Acute, Dofetilide Administration.

    PubMed

    Qiu, Xiaoliang S; Chauveau, Samuel; Anyukhovsky, Evgeny P; Rahim, Tania; Jiang, Ya-Ping; Harleton, Erin; Feinmark, Steven J; Lin, Richard Z; Coronel, Ruben; Janse, Michiel J; Opthof, Tobias; Rosen, Tove S; Cohen, Ira S; Rosen, Michael R

    2016-04-01

    Drugs are screened for delayed rectifier potassium current (IKr) blockade to predict long QT syndrome prolongation and arrhythmogenesis. However, single-cell studies have shown that chronic (hours) exposure to some IKr blockers (eg, dofetilide) prolongs repolarization additionally by increasing late sodium current (INa-L) via inhibition of phosphoinositide 3-kinase. We hypothesized that chronic dofetilide administration to intact dogs prolongs repolarization by blocking IKr and increasing INa-L. We continuously infused dofetilide (6-9 μg/kg bolus+6-9 μg/kg per hour IV infusion) into anesthetized dogs for 7 hours, maintaining plasma levels within the therapeutic range. In separate experiments, myocardial biopsies were taken before and during 6-hour intravenous dofetide infusion, and the level of phospho-Akt was determined. Acute and chronic dofetilide effects on action potential duration (APD) were studied in canine left ventricular subendocardial slabs using microelectrode techniques. Dofetilide monotonically increased QTc and APD throughout 6.5-hour exposure. Dofetilide infusion during ≥210 minutes inhibited Akt phosphorylation. INa-L block with lidocaine shortened QTc and APD more at 6.5 hours than at 50 minutes (QTc) or 30 minutes (APD) dofetilide administration. In comparison, moxifloxacin, an IKr blocker with no effects on phosphoinositide 3-kinase and INa-L prolonged APD acutely but no additional prolongation occurred on chronic superfusion. Lidocaine shortened APD equally during acute and chronic moxifloxacin superfusion. Increased INa-L contributes to chronic dofetilide effects in vivo. These data emphasize the need to include time and INa-L in evaluating the phosphoinositide 3-kinase inhibition-derived proarrhythmic potential of drugs and provide a mechanism for benefit from lidocaine administration in clinical acquired long QT syndrome. © 2016 American Heart Association, Inc.

  17. Iron excretion in iron dextran-overloaded mice

    PubMed Central

    Musumeci, Marco; Maccari, Sonia; Massimi, Alessia; Stati, Tonino; Sestili, Paola; Corritore, Elisa; Pastorelli, Augusto; Stacchini, Paolo; Marano, Giuseppe; Catalano, Liviana

    2014-01-01

    Background Iron homeostasis in humans is tightly regulated by mechanisms aimed to conserve iron for reutilisation, with a negligible role played by excretory mechanisms. In a previous study we found that mice have an astonishing ability to tolerate very high doses of parenterally administered iron dextran. Whether this ability is linked to the existence of an excretory pathway remains to be ascertained. Materials and methods Iron overload was generated by intraperitoneal injections of iron dextran (1 g/kg) administered once a week for 8 weeks in two different mouse strains (C57bl/6 and B6D2F1). Urinary and faecal iron excretion was assessed by inductively coupling plasma-mass spectrometry, whereas cardiac and liver architecture was evaluated by echocardiography and histological methods. For both strains, 24-hour faeces and urine samples were collected and iron concentration was determined on days 0, 1 and 2 after iron administration. Results In iron-overloaded C57bl/6 mice, the faecal iron concentration increased by 218% and 157% on days 1 and 2, respectively (p<0.01). The iron excreted represented a loss of 14% of total iron administered. Similar but smaller changes was also found in B6D2F1 mice. Conversely, we found no significant changes in the concentration of iron in the urine in either of the strains of mice. In both strains, histological examination showed accumulation of iron in the liver and heart which tended to decrease over time. Conclusions This study indicates that mice have a mechanism for removal of excess body iron and provides insights into the possible mechanisms of excretion. PMID:24960657

  18. Ingenious pH-sensitive dextran/mesoporous silica nanoparticles based drug delivery systems for controlled intracellular drug release.

    PubMed

    Zhang, Min; Liu, Jia; Kuang, Ying; Li, Qilin; Zheng, Di-Wei; Song, Qiongfang; Chen, Hui; Chen, Xueqin; Xu, Yanglin; Li, Cao; Jiang, Bingbing

    2017-05-01

    In this work, dextran, a polysaccharide with excellent biocompatibility, is applied as the "gatekeeper" to fabricate the pH-sensitive dextran/mesoporous silica nanoparticles (MSNs) based drug delivery systems for controlled intracellular drug release. Dextran encapsulating on the surface of MSNs is oxidized by NaIO 4 to obtain three kinds of dextran dialdehydes (PADs), which are then coupled with MSNs via pH-sensitive hydrazone bond to fabricate three kinds of drug carriers. At pH 7.4, PADs block the pores to prevent premature release of anti-cancer drug doxorubicin hydrochloride (DOX). However, in the weakly acidic intracellular environment (pH∼5.5) the hydrazone can be ruptured; and the drug can be released from the carriers. The drug loading capacity, entrapment efficiency and release rates of the drug carriers can be adjusted by the amount of NaIO 4 applied in the oxidation reaction. And from which DOX@MSN-NH-N=C-PAD 10 is chosen as the most satisfactory one for the further in vitro cytotoxicity studies and cellular uptake studies. The results demonstrate that DOX@MSN-NH-N=C-PAD 10 with an excellent pH-sensitivity can enter HeLa cells to release DOX intracellular due to the weakly acidic pH intracellular and kill the cells. In our opinion, the ingenious pH-sensitive drug delivery systems have application potentials for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Detecting protein losing enteropathy by Tc-99m dextran scintigraphy: a novel experience.

    PubMed

    Kapoor, Seema; Ratan, Simmi K; Kashyap, Ravi; Mittal, S K; Rajeshwari, K; Rawat, H; Verma, Jyoti

    2002-09-01

    To evaluate protien using enteropathy by Tc-99m dextran scintigraphy. Methods for detecting protein loss from the intestine revolve around fecal nitrogen excretion, the clearance of alpha-1 antitrypsin in stools and by endoscopic biopsy. The diagnosis of protein-losing enteropathy (PLE) can also be established by a scintigraphic method that is noninvasive, simple and requires no patient preparation or motivation. This diagnostic modality can also delineate the site of protein loss, thereby offering a targeted approach, and if need be, surgery. Radiolabelling of a non-protein, noncolloidal, nonparticulate and biofriendly molecule like dextran with Technetium-99m for imaging enteric protein loss was utilized in imaging eight children with PLE. The results were encouraging. The authors advocate the use of this diagnostic tool in identifying patients with PLE, particularly in the pediatric age group.

  20. Dextran hydrogel coated surface plasmon resonance imaging (SPRi) sensor for sensitive and label-free detection of small molecule drugs

    NASA Astrophysics Data System (ADS)

    Li, Shaopeng; Yang, Mo; Zhou, Wenfei; Johnston, Trevor G.; Wang, Rui; Zhu, Jinsong

    2015-11-01

    The label-free and sensitive detection of small molecule drugs on SPRi is still a challenging task, mainly due to the limited surface immobilization capacity of the sensor. In this research, a dextran hydrogel-coated gold sensor chip for SPRi was successfully fabricated via photo-cross-linking for enhanced surface immobilization capacity. The density of the dextran hydrogel was optimized for protein immobilization and sensitive small molecule detection. The protein immobilization capacity of the hydrogel was 10 times greater than a bare gold surface, and 20 times greater than an 11-mercaptoundecanoic acid (MUA) surface. Such a drastic improvement in immobilization capacity allowed the SPRi sensor to detect adequate response signals when probing small molecule binding events. The binding signal of 4 nM liquid-phase biotin to streptavidin immobilized on the dextran surface reached 435 RU, while no response was observed on bare gold or MUA surfaces. The dextran hydrogel-coated SPRi sensor was also applied in a kinetic study of the binding between an immunosuppressive drug (FK506) and its target protein (FKBP12) in a high-throughput microarray format. The measured binding affinity was shown to be consistent with reported literature values, and a detection limit of 0.5 nM was achieved.

  1. MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside.

    PubMed

    Hurtubise, Jessica L; Marks, Wendie N; Davies, Don A; Catton, Jillian K; Baker, Glen B; Howland, John G

    2017-01-01

    The cognitive symptoms observed in schizophrenia are not consistently alleviated by conventional antipsychotics. Following a recent pilot study, sodium nitroprusside (SNP) has been identified as a promising adjunct treatment to reduce the working memory impairments experienced by schizophrenia patients. The present experiments were designed to explore the effects of SNP on the highly translatable trial-unique, delayed nonmatching-to-location (TUNL) task in rats with and without acute MK-801 treatment. SNP (0.5, 1.0, 2.0, 4.0, and 5.0 mg/kg) and MK-801 (0.05, 0.075, and 0.1 mg/kg) were acutely administered to rats trained on the TUNL task. Acute MK-801 treatment impaired TUNL task accuracy. Administration of SNP (2.0 mg/kg) with MK-801 (0.1 mg/kg) failed to rescue performance on TUNL. SNP (5.0 mg/kg) administration nearly 4 h prior to MK-801 (0.05 mg/kg) treatment had no preventative effect on performance impairments. SNP (2.0 mg/kg) improved performance on a subset of trials. These results suggest that SNP may possess intrinsic cognitive-enhancing properties but is unable to block the effects of acute MK-801 treatment on the TUNL task. These results are inconsistent with the effectiveness of SNP as an adjunct therapy for working memory impairments in schizophrenia patients. Future studies in rodents that assess SNP as an adjunct therapy will be valuable in understanding the mechanisms underlying the effectiveness of SNP as a treatment for schizophrenia.

  2. 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

  3. Acute systemic and renal hemodynamic effects of meglumine/sodium diatrizoate 76% and iopamidol in euvolemic and dehydrated dogs.

    PubMed

    Katzberg, R W; Morris, T W; Lasser, E C; DiMarco, P L; Merguerian, P A; Ventura, J A; Pabico, R C; McKenna, B A

    1986-10-01

    We examined the acute systemic and renal hemodynamic effects of intravenous meglumine/sodium diatrizoate-76% and iopamidol in euvolemic and dehydrated dogs. The physiologic responses were compared with acute changes in the level of an endogenous heparin-like material (EHM). One of eight dehydrated dogs receiving diatrizoate (2 ml/kg) had an immediate vomiting reflex associated with a very significant decline in all measured renal hemodynamic parameters; none of eight dehydrated dogs receiving iopamidol experienced a similar reaction. EHM levels did not correspond to the magnitude of the physiologic responses following either iopamidol or diatrizoate. Significant differences between iopamidol and diatrizoate were noted when comparing the magnitude of the decrease in systemic pressure (- delta 3.8 +/- 3.02, iopamidol, n = 8; vs. - delta 19.4 +/- 7.3 mm Hg, diatrizoate, n = 8; P less than .03), increased renal plasma flow (+ delta 6.2 +/- 4.9, iopamidol, n = 8; vs. + delta 33.7 +/- 8.0 ml/min, diatrizoate, n = 8; P less than .05), and decreased filtration fraction (- delta 0.09 +/- 0.01, iopamidol, n = 8; vs. - delta 0.14 +/- 0.02, diatrizoate, n = 8; P less than .03). There was no significant difference in the decrease in glomerular filtration rate (- delta 7.4 +/- 1.0, iopamidol, n = 8; vs. - delta 9.3 +/- 1.3, diatrizoate, n = 8; P greater than .05), since the marked drop in filtration fraction occurring with diatrizoate was counterbalanced by the marked increase in renal plasma flow. Acute systemic and renal hemodynamic effects are significantly lessened when comparing iopamidol with diatrizoate.

  4. 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.

  5. Hybridization chain reaction amplification for highly sensitive fluorescence detection of DNA with dextran coated microarrays.

    PubMed

    Chao, Jie; Li, Zhenhua; Li, Jing; Peng, Hongzhen; Su, Shao; Li, Qian; Zhu, Changfeng; Zuo, Xiaolei; Song, Shiping; Wang, Lianhui; Wang, Lihua

    2016-07-15

    Microarrays of biomolecules hold great promise in the fields of genomics, proteomics, and clinical assays on account of their remarkably parallel and high-throughput assay capability. However, the fluorescence detection used in most conventional DNA microarrays is still limited by sensitivity. In this study, we have demonstrated a novel universal and highly sensitive platform for fluorescent detection of sequence specific DNA at the femtomolar level by combining dextran-coated microarrays with hybridization chain reaction (HCR) signal amplification. Three-dimensional dextran matrix was covalently coated on glass surface as the scaffold to immobilize DNA recognition probes to increase the surface binding capacity and accessibility. DNA nanowire tentacles were formed on the matrix surface for efficient signal amplification by capturing multiple fluorescent molecules in a highly ordered way. By quantifying microscopic fluorescent signals, the synergetic effects of dextran and HCR greatly improved sensitivity of DNA microarrays, with a detection limit of 10fM (1×10(5) molecules). This detection assay could recognize one-base mismatch with fluorescence signals dropped down to ~20%. This cost-effective microarray platform also worked well with samples in serum and thus shows great potential for clinical diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. 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

  7. Genotoxicity, acute and subchronic toxicity studies in rats of a rooster comb extract rich in sodium hyaluronate.

    PubMed

    Canut, Lourdes; Zapatero, Jorge; López, Sílvia; Torrent, Anna; Ruhí, Ramon; Vicente, Laura

    2012-04-01

    The toxicity of a rooster comb extract (IB0004) that contains mainly sodium hyaluronate was assessed in acute and subchronic studies and in a bacterial reverse mutation assay. In a single dose acute study, male and female rats were administered 2000 mg/kg body weight (bw) of the product and observed for 14 days. No mortality was recorded, thus it was considered that the minimum lethal dose for rats by oral route was greater than 2000 mg/kg bw. A 90-day subchronic study (5, 55 and 600 mg/kg bw/day, oral gavage) with 50 male and 50 female Wistar-Hannover rats produced no significant adverse effects on food consumption, body weight, mortality, clinical biochemistry, hematology, gross pathology, and histopathology. Although some differences were observed between the treated and control animals in body weight gain (%) and some hematological parameters, these changes were generally minor in nature and, are considered to be of no toxicological significance. The no-observable-adverse-effects level was established at 600 mg/kg bw/day. There was no evidence of mutagenic activity in Salmonella typhimurium TA98, TA100, TA1535 and TA1537 or in Escherichia coli WP2 uvra pkM101. In conclusion, the results from these safety studies support the safety of rooster comb extract IB0004 in food. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. BCL-2 Modifying Factor (BMF) Is a Central Regulator of Anoikis in Human Intestinal Epithelial Cells*

    PubMed Central

    Hausmann, Martin; Leucht, Katharina; Ploner, Christian; Kiessling, Stephan; Villunger, Andreas; Becker, Helen; Hofmann, Claudia; Falk, Werner; Krebs, Michaela; Kellermeier, Silvia; Fried, Michael; Schölmerich, Jürgen; Obermeier, Florian; Rogler, Gerhard

    2011-01-01

    BCL-2 modifying factor (BMF) is a sentinel considered to register damage at the cytoskeleton and to convey a death signal to B-cell lymphoma 2. B-cell lymphoma 2 is neutralized by BMF and thereby facilitates cytochrome C release from mitochondria. We investigated the role of BMF for intestinal epithelial cell (IEC) homeostasis. Acute colitis was induced in Bmf-deficient mice (Bmf−/−) with dextran sulfate sodium. Colonic crypt length in Bmf−/− mice was significantly increased as compared with WT mice. Dextran sulfate sodium induced less signs of colitis in Bmf−/− mice, as weight loss was reduced compared with the WT. Primary human IEC exhibited increased BMF in the extrusion zone. Quantitative PCR showed a significant up-regulation of BMF expression after initiation of anoikis in primary human IEC. BMF was found on mitochondria during anoikis, as demonstrated by Western blot analysis. RNAi mediated knockdown of BMF reduced the number of apoptotic cells and led to reduced caspase 3 activity. A significant increase in phospho-AKT was determined after RNAi treatment. BMF knockdown supports survival of IEC. BMF is induced in human IEC by the loss of cell attachment and is likely to play an important role in the regulation of IEC survival. PMID:21673109

  9. Efficacy and safety of newly developed cross-linked dextran gel injection for glans penis augmentation with a novel technique

    PubMed Central

    Yang, Dae Yul; Ko, Kyungtae; Lee, Seong Ho; Moon, Du Geon; Kim, Jong Wook; Lee, Won Ki

    2018-01-01

    There is no safe and effective standard method for glans penis augmentation. Furthermore, there has been scant research on glans penis augmentation due to a poor understanding of glans anatomy, technical difficulty, and a lack of suitable substances for augmentation. Cross-linked dextran gel is a newly developed filler for soft-tissue augmentation. We evaluated the efficacy and safety of using a novel technique to inject cross-linked dextran gel for glans penis augmentation during a 24-week follow-up study. This prospective, single-arm, multicenter study enrolled twenty healthy adult men who underwent glans penis augmentation between June and August 2013. Cross-linked dextran gel was injected into the glans penis using a simple and easy technique. The sizes of the glans penis and individual satisfaction were assessed. Any adverse event was also reported. A total of 18 individuals were analyzed; two of them were lost to follow-up. The mean procedure time and injected volume were about 30 min and 6.6 ± 0.9 ml, respectively. The mean surface areas of the glans at baseline and 24 weeks were 20.0 ± 3.5 cm2 and 33.6 ± 5.4 cm2, respectively, representing a mean increase of 68.7% ± 14.0% (P < 0.001). Sixteen individuals (88.9%) were satisfied with the outcomes, and none were dissatisfied. There were no serious adverse events during the study. Cross-linked dextran gel injection for glans penis augmentation was easy and showed a significant augmentative effect on the glans penis, good durability, and was well tolerated without serious adverse events. Therefore, cross-linked dextran gel injection may be an effective, new technique for glans penis augmentation. PMID:28303807

  10. Anesthetic duration of lidocaine with 10% dextran is comparable to lidocaine with 1:160 000 epinephrine after intraosseous injection in the rabbit.

    PubMed

    Ito, Emiko; Ichinohe, Tatsuya; Shibukawa, Yoshiyuki; Aida, Hidetaka; Kaneko, Yuzuru

    2007-09-01

    To compare the effects of 10% dextran and epinephrine on intraosseous injection with lidocaine in rabbits. Twenty male Japanese white rabbits were used. The effect of intraosseous injection was evaluated using an electromyogram (EMG) of the digastric muscle after electrical pulp stimulation. Two percent lidocaine alone (L), 2% lidocaine containing 1:80000 epinephrine (LE8), 2% lidocaine containing 1:160 000 epinephrine (LE16), and 2% lidocaine containing 10% dextran (LD) were tested. Electromyogram recordings were repeated before and 30 seconds, 1, 2, 3, 4, 5, 7, 10, 12, 15, and 20 minutes after the intraosseous injection. Thereafter, recordings were repeated every 5 minutes until the EMG recovered to the control value. There was no difference in the onset time between the 4 groups. The order of the duration of maximum effect was LE8 >LE16 = LD >or=L. The order of the duration of anesthesia was LE8 >LE16 = LD >L. Ten percent dextran potentiates local anesthetic effects of 2% lidocaine in intraosseous injection. The potency of 10% dextran is comparable to 1:160 000 epinephrine.

  11. Enzymatic and acidic degradation of high molecular weight dextran into low molecular weight and its characterizations using novel Diffusion-ordered NMR spectroscopy.

    PubMed

    Iqbal, Samina; Marchetti, Roberta; Aman, Afsheen; Silipo, Alba; Qader, Shah Ali Ul; Molinaro, Antonio

    2017-10-01

    Low molecular weight fractions were derived from native high molecular weight dextran produced by Leuconostoc mesenteroides KIBGE-IB26. Structural characterization of native and low molecular weight fractions obtained after acidic and enzymatic hydrolysis was done using FTIR and NMR spectroscopy. The molecular weight was estimated using Diffusion Ordered NMR spectroscopy. Native dextran (892kDa) is composed of α-(1→6) glycosidic linkage along with α-(1→3) branching. Major proportion of 528kDa dextran was obtained after prolong enzymatic hydrolysis however, an effective acidic treatment at pH-1.4 up to 02 and 04h of exposure resulted in the formation of 77kDa and 57kDa, respectively. The increment in pH from 1.4 to 1.8 lowered the hydrolysis efficiency and resulted in the formation of 270kDa dextran fraction. The results suggest that derived low molecular weight water soluble fractions can be utilized as a drug delivery carrier along with multiple application relating pharmaceutical industries. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Dextran and protamine-based solid lipid nanoparticles as potential vectors for the treatment of X-linked juvenile retinoschisis.

    PubMed

    Delgado, Diego; del Pozo-Rodríguez, Ana; Solinís, Maria Ángeles; Avilés-Triqueros, Marcelino; Weber, Bernhard H F; Fernández, Eduardo; Gascón, Alicia R

    2012-04-01

    The goal of the present study was to analyze the potential application of nonviral vectors based on solid lipid nanoparticles (SLN) for the treatment of ocular diseases by gene therapy, specifically X-linked juvenile retinoschisis (XLRS). Vectors were prepared with SLN, dextran, protamine, and a plasmid (pCMS-EGFP or pCEP4-RS1). Formulations were characterized and the in vitro transfection capacity as well as the cellular uptake and the intracellular trafficking were studied in ARPE-19 cells. Formulations were also tested in vivo in Wistar rat eyes, and the efficacy was studied by monitoring the expression of enhanced green fluorescent protein (EGFP) after intravitreal, subretinal, and topical administration. The presence of dextran and protamine in the SLN improved greatly the expression of retinoschisin and EGFP in ARPE-19 cells. The nuclear localization signals of protamine, its ability to protect the DNA, and a shift in the entry mechanism from caveola-mediated to clathrin-mediated endocytosis promoted by the dextran, justify the increase in transfection. After ocular administration of the dextran-protamine-DNA-SLN complex to rat eyes, we detected the expression of EGFP in various types of cells depending on the administration route. Our vectors were also able to transfect corneal cells after topical application. We have demonstrated the potential usefulness of our nonviral vectors loaded with XLRS1 plasmid and provided evidence for their potential application for the management or treatment of degenerative retinal disorders as well as ocular surface diseases.

  13. Enhancement of Chlamydia trachomatis infectious progeny by cultivation of HeLa 229 cells treated with DEAE-dextran and cycloheximide.

    PubMed Central

    Sabet, S F; Simmons, J; Caldwell, H D

    1984-01-01

    The effects of DEAE-dextran and cycloheximide on the infection of HeLa 229 cells with Chlamydia trachomatis serotype G were studied in terms of the number of cells infected and the yield of infectious progeny per infected cell. Pretreatment of the host cells with DEAE-dextran resulted in an increase in the number of infected cels but had no significant effect on the yield of infectious progeny per infected cell (burst size). In contrast, the addition of cycloheximide to the medium of infected cells had no significant effect on the number of infected cells but greatly enhanced the burst size. The burst size was calculated to be close to 500. The enhanced burst size was also observed in cells treated with DEAE-dextran and cycloheximide. In addition, there was an increase in the number of cells infected and an augmentation of the infectious progeny yield. Under the conditions of combined treatment, the yield of C. trachomatis serotype G cultivated in HeLa 229 cells was found to be approximately threefold higher than the yield of the organisms cultivated in McCoy cells. The results suggest that HeLa 229 cells treated with DEAE-dextran and cycloheximide offer a most suitable system for the high-yield cultivation of C. trachomatis organisms and possibly also for the diagnosis of infection with these organisms. Images PMID:6208215

  14. Effect of thiopental sodium on N-methyl-D-aspartate-gated currents.

    PubMed

    Liu, Hongliang; Dai, Tijun; Yao, Shanglong

    2006-05-01

    N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex (PFC) are closely related with the excitability of pyramidal neurons and PFC function. As the effect of thiopental sodium on the central nervous system may partly result from the inhibition of PFC NMDA receptors, we investigated the effect of thiopental sodium with different concentrations on NMDA-gated currents in acutely dissociated rat PFC pyramidal neurons. We sought to determine whether thiopental sodium inhibits NMDA receptor function. Three to four week old male Sprague-Dawley rats were sacrificed and the PFC was dissected. Pyramidal neurons from the PFC were prepared and standard whole-cell patch clamp recordings were performed. Escalating concentrations from 3-1000 microM NMDA were applied 100 microm from the pyramidal cells, and the concentration in the effect compartment related to 50% effect (EC50) of NMDA was determined for the ensuing experiments. One hundred microM NMDA alone (control) or NMDA with different concentrations (10-1000 microM) of thiopental sodium were applied. After the inhibitory concentration, in 50% of NMDA effect (IC50) of thiopental sodium was established this IC50 and NMDA 3-1000 microM were applied 100 microm from the pyramidal cells. The EC50 value of NMDA under the effect of IC50 thiopental sodium was determined. N-methyl-D-aspartate induced inward currents in a concentration-dependent manner, which were completely antagonized by 50 microM AP5. The maximal amplitude of NMDA-induced current was 1.15 +/- 0.27 nA. The EC50 of NMDA was 53.6 +/- 12.4 microM. The NMDA (100 microM)-gated current was inhibited by thiopental sodium in a concentration-dependent manner, and the IC50 of thiopental sodium was 33.6 +/- 6.1 microM. Under the effect of 33.6 microM thiopental sodium, the maximal amplitude of NMDA-induced current was 0.87 +/- 0.17 nA. The concentration-response curve of NMDA was shifted rightwards. The EC50 of NMDA was 128 +/- 15 microM, which was greater than that

  15. Soy protein supports cardiovascular health by downregulating hydroxymethylglutaryl-coenzyme A reductase and sterol regulatory element-binding protein-2 and increasing antioxidant enzyme activity in rats with dextran sodium sulfate-induced mild systemic inflammation.

    PubMed

    Marsh, Tanya G; Straub, Rachel K; Villalobos, Fatima; Hong, Mee Young

    2011-12-01

    Animal and human studies have indicated that the presence of soy in the diet improves cardiovascular health. Inflammation plays a pivotal role in the progression of cardiovascular disease (CVD). However, little is known about how dextran sodium sulfate (DSS)-induced systemic inflammation impacts overall heart health and, correspondingly, how soy protein modulates risk of CVD development in DSS-induced systemic inflammation. We hypothesized that soy protein-fed rats would have a lower risk of CVD by beneficial alteration of gene expression involving lipid metabolism and antioxidant capacity in DSS-induced systemic inflammation. Forty Sprague-Dawley rats were divided into 4 groups: casein, casein + DSS, soy protein, and soy protein + DSS. After 26 days, inflammation was induced in one group from each diet by incorporating 3% DSS in drinking water for 48 hours. Soy protein-fed rats had lower final body weights (P = .010), epididymal fat weights (P = .049), total cholesterol (P < .001), and low-density lipoprotein cholesterol (P < .001). In regard to gene expression, soy protein-fed rats had lower sterol regulatory element-binding protein-2 (P = .032) and hydroxymethylglutaryl-coenzyme A reductase (P = .028) levels and higher low-density lipoprotein receptor levels (P = .036). Antioxidant enzyme activity of superoxide dismutase and catalase was higher among the soy protein groups (P = .037 and P = .002, respectively). These results suggest that soy protein positively influences cardiovascular health by regulating serum lipids through modified expression of sterol regulatory element-binding protein-2 and its downstream genes (ie, hydroxymethylglutaryl-coenzyme A reductase and low-density lipoprotein receptor) and by promoting the antioxidant enzyme activity of superoxide dismutase and catalase. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. The frequently used intraperitoneal hyponatraemia model induces hypovolaemic hyponatraemia with possible model-dependent brain sodium loss.

    PubMed

    Overgaard-Steensen, Christian; Stødkilde-Jørgensen, Hans; Larsson, Anders; Tønnesen, Else; Frøkiaer, Jørgen; Ring, Troels

    2016-07-01

    What is the central question of this study? The brain response to acute hyponatraemia is usually studied in rodents by intraperitoneal instillation of hypotonic fluids (i.p. model). The i.p. model is described as 'dilutional' and 'syndrome of inappropriate ADH (SIADH)', but the mechanism has not been explored systematically and might affect the brain response. Therefore, in vivo brain and muscle response were studied in pigs. What is the main finding and its importance? The i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution, not dilution. A large reduction in brain sodium is observed, probably because of the specific mechanism causing the hyponatraemia. This is not accounted for in current understanding of the brain response to acute hyponatraemia. Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe morbidity and even death may occur. Experimentally, acute hyponatraemia is most frequently studied in small animal models, in which the hyponatraemia is produced by intraperitoneal instillation of hypotonic fluids (i.p. model). This hyponatraemia model is described as 'dilutional' or 'syndrome of inappropriate ADH (SIADH)', but seminal studies contradict this interpretation. To confront this issue, we developed an i.p. model in a large animal (the pig) and studied water and electrolyte responses in brain, muscle, plasma and urine. We hypothesized that hyponatraemia was induced by simple water dilution, with no change in organ sodium content. Moderate hypotonic hyponatraemia was induced by a single i.v. dose of desmopressin and intraperitoneal instillation of 2.5% glucose. All animals were anaesthetized and intensively monitored. In vivo brain and muscle water was determined by magnetic resonance imaging and related to the plasma sodium concentration. Muscle water content increased less than expected as a result of pure dilution, and muscle sodium content decreased significantly (by 28

  17. 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.

  18. How Strong Is the Evidence for Sodium Bicarbonate to Prevent Contrast-Induced Acute Kidney Injury After Coronary Angiography and Percutaneous Coronary Intervention?

    PubMed

    Dong, Yuhao; Zhang, Bin; Liang, Long; Lian, Zhouyang; Liu, Jing; Liang, Changhong; Zhang, Shuixing

    2016-02-01

    Hydration with sodium bicarbonate is one of the strategies to prevent contrast-induced acute kidney injury (CI-AKI). The purpose of this study was to determine how strong is the evidence for sodium bicarbonate to prevent CI-AKI after coronary angiography (CAG) and/or percutaneous coronary intervention (PCI).We conducted PubMed, EMBASE, and CENTRAL databases to search for randomized controlled trials (RCTs) comparing the efficacy of sodium bicarbonate with sodium chloride to prevent CI-AKI after CAG and/or PCI. Relative risk (RR), standardized mean difference (SMD), or weighted mean difference (WMD) with 95% confidence intervals (CIs) was calculated. Heterogeneity, publication bias, and study quality were evaluated, sensitivity analyses, cumulative analyses, and subgroup analyses were performed. The risk of random errors was assessed by trial sequential analysis (TSA).Sixteen RCTs (3537 patients) met the eligibility criteria. Hydration with sodium bicarbonate showed significant beneficial effects in preventing CI-AKI (RR 0.67; 95% CI: 0.47-0.96, P = 0.029), decreasing the change in serum creatinine (SCr) (SMD -0.31 95% CI: -0.55 to -0.07, P = 0.011) and estimated glomerular filtration rate (eGFR) (SMD -0.17 95% CI: -0.30 to -0.04, P = 0.013). But no significant differences were observed in the requirement for dialysis (RR 1.11; 95% CI: 0.60-2.07, P = 0.729), mortality (RR 0.71; 95% CI: 0.41-1.21, P = 0.204) and reducing the length of hospital stay (LHS) (WMD -1.47; 95% CI: -4.14 to 1.20, P = 0.279). The result of TSA on incidence of CI-AKI showed the required information size (RIS = 6614) was not reached and cumulative z curve did not cross TSA boundary. The result of TSA on the requirement for dialysis and mortality demonstrated the required information sizes (RIS = 170,510 and 19,516, respectively) were not reached, and the cumulative z-curve did not cross any boundaries.The evidence that sodium bicarbonate reduces the incidence of

  19. In vitro evaluation of the effect of haemodilution with dextran 40 on coagulation profile as measured by thromboelastometry and multiple electrode aggregometry.

    PubMed

    Kam, Pca; Liou, Jpc; Yang, Kxf

    2017-09-01

    We evaluated the effects of haemodilution with either dextran 40 or 0.9% normal saline on coagulation in vitro using rotational thromboelastometry (ROTEM®, Pentapharm Co., Munich, Germany) and multiple electrode aggregometry (Multiplate® Platelet Function Analyser, Dynabyte, Munich, Germany). Venous blood samples obtained from 20 healthy volunteers were diluted in vitro with dextran 40 or normal saline by 5%, 10% and 15%. Fibrinogen concentration, ROTEM-EXTEM® (screening test for the extrinsic coagulation pathway), FIBTEM® (an EXTEM-based assay of the fibrin component of clot) parameters including coagulation time, clot formation time, alpha angle, maximum clot firmness and lysis index were measured in the undiluted sample and at each level of haemodilution. Dextran 40 at 15% haemodilution significantly prolonged coagulation time, clot formation time and significantly decreased the alpha angle and maximal clot firmness (EXTEM amplitude at five minutes [A5] and ten minutes [A10]) compared with normal saline. The FIBTEM assay (maximal clot firmness and FIBTEM A5 and A10) showed a marked decrease in maximal clot firmness at all dilutions suggesting impaired fibrinogen activity and a risk of bleeding. Multiple electrode aggregometry did not demonstrate any platelet dysfunction. Haemodilution with dextran 40 causes significant impairment in clot formation and strength compared to saline haemodilution and undiluted blood. At the levels of in vitro haemodilution designed to reflect the clinical use of dextran infusions, no significant fibrinolysis or platelet inhibition was observed.

  20. Fabrication and characterization of ultrathin dextran layers: Time dependent nanostructure in aqueous environments revealed by OWLS.

    PubMed

    Saftics, Andras; Kurunczi, Sándor; Szekrényes, Zsolt; Kamarás, Katalin; Khánh, Nguyen Quoc; Sulyok, Attila; Bősze, Szilvia; Horvath, Robert

    2016-10-01

    Surface coatings of the polysaccharide dextran and its derivatives are key ingredients especially in label-free biosensors for the suppression of non-specific binding and for receptor immobilization. Nevertheless, the nanostructure of these ultrathin coatings and its tailoring by the variation of the preparation conditions have not been profoundly characterized and understood. In this work carboxymethylated dextran (CMD) was prepared and used for fabricating ultrathin surface coatings. A grafting method based on covalent coupling to aminosilane- and epoxysilane-functionalized surfaces was applied to obtain thin CMD layers. The carboxyl moiety of the CMD was coupled to the aminated surface by EDC-NHS reagents, while CMD coupling through epoxysilane molecules was performed without any additional reagents. The surface analysis following the grafting procedures consisted of X-ray photoelectron spectroscopy (XPS), attenuated total reflection infrared spectroscopy (ATR-IR), spectroscopic ellipsometry, atomic force microscopy (AFM) and optical waveguide lightmode spectroscopy (OWLS). The XPS and AFM measurements showed that the grafting resulted in a very thin dextran layer of a few nanometers. The OWLS method allowed devising the structure of the interfacial dextran layers by the evaluation of the optogeometrical parameters. The alteration in the nanostructure of the CMD layer with the chemical composition of the silane coverage and the pH of the grafting solution was revealed by in situ OWLS, specifically, lain down chains were found to be prevalent on the surface under neutral and basic conditions on epoxysilylated surfaces. The developed methodologies allowed to design and fabricate nanometer scale CMD layers with well-controlled surface structure, which are very difficult to characterize in aqueous environments using present instrumentations and highly hydrated surface layers. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Hydration Dynamics of Hyaluronan and Dextran

    PubMed Central

    Hunger, Johannes; Bernecker, Anja; Bakker, Huib J.; Bonn, Mischa; Richter, Ralf P.

    2012-01-01

    Hyaluronan is a polysaccharide, which is ubiquitous in vertebrates and has been reported to be strongly hydrated in a biological environment. We study the hydration of hyaluronan in solution using the rotational dynamics of water as a probe. We measure these dynamics with polarization-resolved femtosecond-infrared and terahertz time-domain spectroscopies. Both experiments reveal that a subensemble of water molecules is slowed down in aqueous solutions of hyaluronan amounting to ∼15 water molecules per disaccharide unit. This quantity is consistent with what would be expected for the first hydration shell. Comparison of these results to the water dynamics in aqueous dextran solution, a structurally similar polysaccharide, yields remarkably similar results. This suggests that the observed interaction with water is a common feature for hydrophilic polysaccharides and is not specific to hyaluronan. PMID:22828349

  2. Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction

    PubMed Central

    Russell, Richard O.; Rackley, Charles E.; Pombo, Jaoquin; Hunt, David; Potanin, Constantine; Dodge, Harold T.

    1970-01-01

    Left ventricular performance in 19 patients with acute myocardial infarction has been evaluated by measuring left ventricular response in terms of cardiac output, stroke volume, work, and power to progressive elevation of filling pressure accomplished by progressive expansion of blood volume with rapid infusion of low molecular weight dextran. Such infusion can elevate the cardiac output, stroke volume, work, and power and thus delineate the function of the left ventricle by Frank-Starling function curves. Left ventricular filling pressure in the range of 20-24 mm Hg was associated with the peak of the curves and when the filling pressure exceeded this range, the curves became flattened or decreased. An increase in cardiac output could be maintained for 4 or more hr. Patients with a flattened function curve had a high mortality in the ensuing 8 wk. The function curve showed improvement in myocardial function during the early convalescence. When left ventricular filling pressure is monitored directly or as pulmonary artery end-diastolic pressure, low molecular weight dextran provides a method for assessment of left ventricular function. Images PMID:5431663

  3. Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload.

    PubMed

    Pardo Andreu, G L; Inada, N M; Vercesi, A E; Curti, C

    2009-01-01

    One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21 +/- 4 to 130 +/- 7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H+ leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria.

  4. Alpha 1-acid glycoprotein reverses cocaine-induced sodium channel blockade in cardiac myocytes.

    PubMed

    Ma, Yu-Ling; Peters, Nicholas S; Henry, John A

    2006-03-01

    Alpha 1-acid glycoprotein (AAG) is an acute phase protein capable of binding basic drugs. This action explains its reversal of sodium channel blockade by drugs such as amitriptyline and quinidine. We report here the reversal of cocaine-induced sodium channel blockade by AAG. The sodium channel blocking property of cocaine is a major mechanism behind cocaine-induced sudden cardiac death, since sodium channels play a key role in the initiation and regulation of the heart beat. Voltage-gated sodium current (I(Na)) was recorded using whole-cell patch-clamp techniques. Guinea-pig cardiac ventricular myocytes were isolated and continuously perfused at room temperature with physiological solutions. At concentrations ranging from 5 to 320 microM cocaine showed a dose-dependent and reversible blockade of I(Na) with an IC50 of 45.9 microM. The addition of equimolar amounts of AAG to cocaine produced almost complete reversal of cocaine's effects, suggesting a single binding site for cocaine on the AAG molecule. With changes of peak I(Na) normalized against control as 1, cocaine at 20 and 40 microM reduced I(Na) to 0.62+/-0.042 (n = 6) and 0.57+/-0.052 (n = 9), respectively, and the addition of an equimolar concentration of AAG reversed I(Na) to 0.86+/-0.022 and 0.91+/-0.060, respectively. AAG reverses cocaine-induced sodium channel blockade in a dose-dependent manner, indicating a therapeutic potential to reverse acute cocaine cardiac toxicity.

  5. Dextran or Saline Can Replace Contrast for Intravascular Optical Coherence Tomography in Lower Extremity Arteries.

    PubMed

    Kendrick, Daniel E; Allemang, Matthew T; Gosling, Andre F; Nagavalli, Anil; Kim, Ann H; Nishino, Setsu; Parikh, Sahil A; Bezerra, Hiram G; Kashyap, Vikram S

    2016-10-01

    To examine the hypothesis that alternative flush media could be used for lower extremity optical coherence tomography (OCT) imaging in long lesions that would normally require excessive use of contrast. The OPTical Imaging Measurement of Intravascular Solution Efficacy (OPTIMISE) trial was a single-center, prospective study (ClinicalTrials.gov identifier NCT01743872) that enrolled 23 patients (mean age 68±11 years; 14 men) undergoing endovascular intervention involving the superficial femoral artery. Four flush media (heparinized saline, dextran, carbon dioxide, and contrast) were used in succession in random order for each image pullback. Quality was defined as ≥270° visualization of vessel wall layers from each axial image. Mean proportions (± standard deviation) of image quality for each flush medium were assessed using 1-way analysis of variance and are reported with the 95% confidence intervals (CI). Four OCT catheters failed, leaving 19 patients who completed the OCT imaging protocol; from this cohort, 51 highest quality runs were selected for analysis. Average vessel diameter was 3.99±1.01 mm. OCT imaging allowed 10- to 15-μm resolution of the lumen border, with diminishing quality as vessel diameter increased. Plaque characterization revealed fibrotic lesions. Mean proportions of image quality were dextran 87.2%±12% (95% CI 0.81 to 0.94), heparinized saline 74.3%±24.8% (95% CI 0.66 to 0.93), contrast 70.1%±30.5% (95% CI 0.52 to 0.88), and carbon dioxide 10.0%±10.4% (95% CI 0.00 to 0.26). Dextran, saline, and contrast provided better quality than carbon dioxide (p<0.001). OCT is feasible in peripheral vessels <5 mm in diameter. Dextran or saline flush media can allow lesion characterization, avoiding iodinated contrast. Carbon dioxide is inadequate for peripheral OCT imaging. Axial imaging may aid in enhancing durability of peripheral endovascular interventions. © The Author(s) 2016.

  6. Separation of pharmacologically active nitrogen-containing compounds on silica gels modified with 6,10-ionene, dextran sulfate, and gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Ioutsi, A. N.; Shapovalova, E. N.; Ioutsi, V. A.; Mazhuga, A. G.; Shpigun, O. A.

    2017-12-01

    New stationary phases for HPLC are obtained via layer-by-layer deposition of polyelectrolytes and studied: (1) silica gel modified layer-by-layer with 6,10-ionene and dextran sulfate (Sorbent 1); (2) silica gel twice subjected to the above modification (Sorbent 2); and (3) silica gel modified with 6,10-ionene, gold nanoparticles, and dextran sulfate (Sorbent 3). The effect the content of the organic solvent in the mobile phase and the concentration and pH of the buffer solution have on the chromatographic behavior of several pharmacologically active nitrogen-containing compounds is studied. The sorbents are stable during the process and allow the effective separation of beta-blockers, calcium channel blockers, alpha-agonists, and antihistamines. A mixture of caffeine, nadolol, tetrahydrozoline, pindolol, orphenadrine, doxylamine, carbinoxamine, and chlorphenamine is separated in 6.5 min on the silica gel modified with 6,10-ionene, gold nanoparticles, and dextran sulfate.

  7. Role of dextran in maintaining adhesive and stiffness properties of prestripped DMEK lenticules.

    PubMed

    Parekh, Mohit; Ruzza, Alessandro; Di Mundo, Rosa; Ferrari, Stefano; Recchia, Giuseppina; Elbadawy, Hossein; Carbone, Giuseppe; Ponzin, Diego

    2017-05-11

    To investigate the adhesive and stiffness properties of prestripped Descemet membrane endothelial keratoplasty (DMEK) lenticules in different preservation conditions (with and without dextran). The study included 3 conditions: (C1) tissues collected from tissue culture media (TCM), stripped and preserved in TCM; (C2) tissues collected from transport media (TM) (TCM supplemented with 6% dextran T-500), stripped and preserved in TM; and (C3) tissues collected from TCM, stripped and preserved in TM. Using a hinge, 9.5-mm stripped DMEK lenticules were restored back on the stroma and preserved for 4 days at room temperature (RT) in different conditions as above. Nine tissues, 3 from each condition, were used to check the adhesive (fibronectin, laminin, and vitronectin) and elastic properties (fibrillin, elastin, and collagen VI) using different antibodies. Six tissues, 2 from each condition, were used to check the stiffness properties after preservation using atomic force microscopy (AFM) nanoindentation method. On the Descemet membrane, fibronectin was strongly expressed in C2 and C3, whereas laminin was intense in C2 postpreservation. Vitronectin was expressed in all the conditions. Elastic proteins were not expressed in either of the conditions apart from collagen VI, which was expressed on the posterior stroma. Atomic force microscopy showed higher stiffness in C3 and an insignificant but lower rigidity in C2 as compared to C1. The tissues from C2 showed expression of adherent proteins and lower stiffness. Dextran may be suitable in preservation of DMEK grafts before and after preparation. Less stiff tissues may help reduce manipulations required in the recipient eye during DMEK surgery.

  8. Thiolated polycarbophil/glutathione: defining its potential as a permeation enhancer for oral drug administration in comparison to sodium caprate.

    PubMed

    Perera, Glen; Barthelmes, Jan; Vetter, Anja; Krieg, Christof; Uhlschmied, Cindy; Bonn, Günther K; Bernkop-Schnürch, Andreas

    2011-08-01

    Thiolated polyacrylates were shown to be permeation enhancers with notable potential. The aim of this study was to evaluate the permeation enhancing properties of a thiolated polycarbophil/glutathione (PCP-Cys/GSH) system for oral drug application in comparison to a well-established permeation enhancer, namely sodium caprate. In vitro permeation studies were conducted in Ussing-type chambers with sodium fluoresceine (NaFlu) and fluoresceine isothiocyanate labeled dextran (molecular mass 4 kDa; FD4) as model compounds. Bioavailability studies were carried out in Sprague Dawley rats with various formulations. Moreover, cytotoxic effects of both permeation enhancers were compared. Permeation enhancement ratios of 1% sodium caprate were found to be 3.0 (FD4) and 2.3 (NaFlu), whereas 1% PCP-Cys/0.5% GSH displayed enhancement ratios of 2.4 and 2.2. Both excipients performed at a similar level in vivo. Sodium caprate solutions increased oral bioavailability 2.2-fold (FD4) and 2.3-fold (NaFlu), while PCP-Cys hydrogels led to a 3.2-fold and 2.2-fold enhancement. Cell viability experiments revealed a significantly higher tolerance of Caco-2 cells towards 0.5% PCP-Cys (81% survival) compared to 0.5% sodium caprate (5%). As PCP-Cys is not absorbed from mucosal membranes due to its comparatively high molecular mass, systemic side-effects can be excluded. In conclusion, both systems displayed a similar potency for permeation enhancement of hydrophilic compounds. However, PCP-Cys seems to be less harmful to cultured cells.

  9. Loxoprofen--another NSAID associated with acute asthmatic death.

    PubMed

    Watanabe, T; Sakata, M; Shimabukuro, R; Sakata, K; Tabata, N; Azumi, J; Morita, M; Itaya, K

    1993-01-01

    Loxoprofen sodium (sodium 2[4-(2-oxocyclopentylmethyl) phenyl] dehydrate; CAS #68767-14-6) is a nonsteroidal, inflammatory drug marketed only in Japan. A case report describes its association with an acute asthmatic death with features resembling those evoked by similar drugs. The analytic methodology is reported. The blood levels of loxoprofen were in the therapeutic range. The tissue concentrations are reported.

  10. Chronic intermittent psychosocial stress (social defeat/overcrowding) in mice increases the severity of an acute DSS-induced colitis and impairs regeneration.

    PubMed

    Reber, S O; Obermeier, F; Straub, R H; Straub, H R; Falk, W; Neumann, I D

    2006-10-01

    Ulcerative colitis is a multifactorial disease, with immunological, genetic, and environmental factors playing an important role in its pathogenesis. Here we investigated the consequences of exposure to chronic psychosocial stress on the severity of a dextran sulfate sodium (DSS)-induced colitis in male C57BL/6 mice. Chronic stress was induced by repeated exposure to social defeat (SD, 2 h) and overcrowding (OC, 24 h) during 19 consecutive days. SD/OC mice showed a diminished body weight gain, thymus-atrophy, and adrenal hypertrophy, but similar light-phase plasma corticosterone concentrations, compared with unstressed mice. In contrast, the rise in dark-phase corticosterone concentration was significantly attenuated in SD/OC mice, whereas plasma ACTH concentrations and hypothalamic CRH mRNA expression did not differ between stressed and nonstressed groups. Additionally, adrenal cells from SD/OC mice showed a decreased in vitro response to ACTH stimulation. Subsequent treatment with 1% DSS for 7 d resulted in a more severe intestinal inflammation in SD/OC mice, as reflected by an increase in body weight loss, histological damage scores, and secretion of IL-6, TNFalpha, and interferon-gamma from mesenteric lymph node cells and by decreased colon length. The impaired health status of stressed mice was also reflected by a significantly lower survival rate after termination of the DSS treatment. In conclusion, the present findings demonstrate that chronic intermittent exposure to a psychosocial stressor before the induction of acute DSS-colitis results in adrenal insufficiency, increases in the severity of the acute inflammation, and impairs the healing phase.

  11. Dextran based herbal nanobiocomposite membranes for scar free wound healing.

    PubMed

    Singh, Surabhi; Gupta, Amlan; Sharma, Deepika; Gupta, Bhuvanesh

    2018-07-01

    Dextran based bionanocomposite membranes encapsulating clove oil (CO) and sandalwood oil (SO) that are capable of preventing infection due to their inherent virtue of antibacterial activity and modifying the wound healing cascade for accelerated scar free healing, were developed. A facile solvent casting technique was used to fabricate dextran/nanosoy/glycerol/chitosan (DNG/Ch) nanocomposite membranes followed by subsequent addition of CO and SO to obtain DNG/Ch/CO and DNG/Ch/SO herbal nanodressings. Dressings exhibited >98% antibacterial activity against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) at extremely low loadings of 5% and 10% for CO and SO, respectively. This encapsulation strategy allowed controlled diffusion of EO over a period of 72h which was measured in terms of drug efficacy using bacterial reduction count test and serial plate transfer disk diffusion test (SPTDDT). Swelling behavior and mechanical properties were also examined. Bacterial adherence study was performed to demonstrate the efficiency of dressings for arresting microbial invasion. In vivo wound healing studies were conducted using male swiss albino mice of BALB/c strain and DNG/Ch/CO dressings exhibited complete healing within 14days with remarkable efficacy in scar prevention. Histological analysis revealed that CO and SO treatment led to deposition of ordered collagen along with fibroblast migration. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. [Sodium valproate as a cause of acute pancreatitis: a case report].

    PubMed

    Barreda, Luís; Rosas, Johana; Milian, William; Valdivia, Duilio; Targarona, Javier

    2006-01-01

    Valproic acid (VPA) is a commonly used medication approved by the U.S. FDA for the treatment of epilepsy, migraines and bipolar disorders. Adverse effects associated with VPA are typically benign, but there are more serious effects that are less frequent. These effects include hepatotoxicity, teratogenicity, possible polycystic ovaries with a potential sterile effect and acute pancreatitis. Even though acute pancreatitis is an adverse effect of very low frequency, it is very important due to the high mortality rate of patients with acute pancreatitis as a consequence of the use of valproic acid. In medical literature, by 2005, 80 cases of acute pancreatitis caused by valproic acid were reported, 33 of these cases were patients under the age of 18. This is a description of the clinical case of a 16 year old patient with necrotic pancreatitis caused by VPA, who was treated at the Acute Pancreatitis Unit of Edgardo Rebagliati Martins National Hospital.

  13. Detecting Levels of Polyquaternium-10 (PQ-10) via Potentiometric Titration with Dextran Sulphate and Monitoring the Equivalence Point with a Polymeric Membrane-Based Polyion Sensor.

    PubMed

    Ferguson, Stephen A; Wang, Xuewei; Meyerhoff, Mark E

    2016-08-07

    Polymeric quaternary ammonium salts (polyquaterniums) have found increasing use in industrial and cosmetic applications in recent years. More specifically, polyquaternium-10 (PQ-10) is routinely used in cosmetic applications as a conditioner in personal care product formulations. Herein, we demonstrate the use of potentiometric polyion-sensitive polymeric membrane-based electrodes to quantify PQ-10 levels. Mixtures containing both PQ-10 and sodium lauryl sulfate (SLS) are used as model samples to illustrate this new method. SLS is often present in cosmetic samples that contain PQ-10 (e.g., shampoos, etc.) and this surfactant species interferes with the polyion sensor detection chemistry. However, it is shown here that SLS can be readily separated from the PQ-10/SLS mixture by use of an anion-exchange resin and that the PQ-10 can then be titrated with dextran sulphate (DS). This titration is monitored by potentiometric polyanion sensors to provide equivalence points that are directly proportional to PQ-10 concentrations.

  14. Nedocromil sodium reduces cigarette smoke-induced bronchoconstrictor hyperresponsiveness to substance P in the guinea-pig.

    PubMed

    Dusser, D J; Lacroix, H; Desmazes-Dufeu, N; Mordelet-Dambrine, M; Roisman, G L

    1995-01-01

    Acute exposure to cigarette smoke provokes airway hyperresponsiveness to substance P and inactivates neutral endopeptidase (NEP). To determine whether nedocromil sodium can prevent cigarette smoke-induced hyperresponsiveness to substance P, we studied two groups of anaesthetized guinea-pigs. One group of guinea-pigs was pretreated with aerosolized 0.9% NaCl solution (90 breaths), the other group was pretreated with aerosolized nedocromil sodium (10(-4) M, 90 breaths). In each animal, pretreatment was followed by either exposure to the smoke of one cigarette or exposure to air. After acute exposure to cigarette smoke or to air, we measured the change in total pulmonary resistance (RL) induced by increasing concentrations of aerosolized substance P. In the absence of nedocromil sodium, the bronchoconstrictor responses to substance P were greater in cigarette smoke-exposed guinea-pigs than in air-exposed animals. Aerosolized nedocromil sodium had no effect on the response to substance P in air-exposed animals, but it reduced cigarette smoke-induced hyperresponsiveness to substance P. The preventive effect on cigarette smoke-induced hyperresponsiveness to substance P was observed at concentrations of aerosolized nedocromil sodium of 3 x 10(-5), 10(-4), and 3 x 10(-4) M. In vitro, cigarette smoke solution inhibited NEP activity from lung membrane preparations, but this inhibitory effect was not modified by nedocromil sodium (10(-4) M). We conclude that aerosolized nedocromil sodium reduces cigarette smoke-induced airway hyperresponsiveness to substance P in vivo. This action of nedocromil sodium is not due to a protective effect on cigarette smoke-induced inactivation of NEP in vitro.

  15. Hepatoprotective effect of Taraxacum officinale leaf extract on sodium dichromate-induced liver injury in rats.

    PubMed

    Hfaiedh, Mbarka; Brahmi, Dalel; Zourgui, Lazhar

    2016-03-01

    Taraxacum officinale (L.) Weber, commonly known as Dandelion, has been widely used as a folkloric medicine for the treatment of liver and kidney disorders and some women diseases such as breast and uterus cancers. The main objective of the present study was to assess the efficiency of T. officinale leaf extract (TOE) in treating sodium dichromate hazards; it is a major environmental pollutant known for its wide toxic manifestations witch induced liver injury. TOE at a dose of 500 mg/kg b.w was orally administered once per day for 30 days consecutively, followed by 10 mg/kg b.w sodium dichromate was injected (intraperitoneal) for 10 days. Our results using Wistar rats showed that sodium dichromate significantly increased serum biochemical parameters. In the liver, it was found to induce an oxidative stress, evidenced from increase in lipid peroxidation and changes in antioxidative activities. In addition, histopathological observation revealed that sodium dichromate causes acute liver damage, necrosis of hepatocytes, as well as DNA fragmentation. Interestingly, animals that were pretreated with TOE, prior to sodium dichromate administration, showed a significant hepatoprotection, revealed by a significant reduction of sodium dichromate-induced oxidative damage for all tested markers. These finding powerfully supports that TOE was effective in the protection against sodium dichromate-induced hepatotoxicity and genotoxicity and, therefore, suggest a potential therapeutic use of this plant as an alternative medicine for patients with acute liver diseases. © 2014 Wiley Periodicals, Inc.

  16. Segmental sodium reabsorption by the renal tubule in prenatally programmed hypertension in the rat.

    PubMed

    Alwasel, Saleh H; Ashton, Nick

    2012-02-01

    Hypertension and renal dysfunction can be programmed in the rat by prenatal exposure to a low-protein (LP) diet. Expression of the renal thick ascending limb (TAL) sodium transporter NKCC2 is up-regulated, which has been predicted to result in greater sodium reabsorption. However, we have shown that LP rats excrete more not less sodium. The aim of this study was to determine whether the increased abundance of sodium:potassium:chloride (Na(+):K(+):2Cl(-)) co-transporter (NKCC2) leads to enhanced sodium uptake by the TAL. Pregnant Wistar rats were fed a control (18%) or LP (9%) diet. Amiloride (AM), bendroflumethiazide (BF), and furosemide (FUR) were administered acutely to male offspring at 4 weeks of age. Fractional excretion of sodium (FE(Na)) was significantly greater in vehicle-infused LP rats (3.0 ± 0.3%) compared with controls (1.7 ± 0.5, P < 0.01). FE(Na) by the LP proximal tubule did not differ from controls, whereas FE(Na) by the distal tubule was significantly greater (P < 0.01). These differences were abolished by the administration of AM + BF (equivalent to the outflow from the TAL) and AM + BF + FUR (equivalent to the outflow from the proximal tubule), suggesting that the increase in NKCC2 expression was not functional. However, during acute salt loading, the LP rat pressure natriuresis curve was shifted rightward, implying that raised systemic blood pressure is required to match urinary sodium excretion with dietary intake. These data suggest that renal sodium handling is impaired in the LP rat but that this is not due to increased NKCC2 expression.

  17. Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance

    PubMed Central

    Simberg, Dmitri; Park, Ji-Ho; Karmali, Priya P.; Zhang, Wan-Ming; Merkulov, Sergei; McCrae, Keith; Bhatia, Sangeeta; Sailor, Michael; Ruoslahti, Erkki

    2009-01-01

    In order to understand the role of plasma proteins in the rapid liver clearance of dextran-coated superparamagnetic iron oxide (SPIO) in vivo, we analyzed the full repertoire of SPIO-binding blood proteins using novel two-dimensional differential mass spectrometry approach. The identified proteins showed specificity for surface domains of the nanoparticles: mannan-binding lectins bound to the dextran coating, histidine-rich glycoprotein and kininogen bound to the iron oxide part, and the complement lectin and contact clotting factors were secondary binders. Nanoparticle clearance studies in knockout mice suggested that these proteins, as well as several previously identified opsonins, do not play a significant role in the SPIO clearance. However, both the dextran coat and the iron oxide core remained accessible to specific probes after incubation of SPIO in plasma, suggesting that the nanoparticle surface could be available for recognition by macrophages, regardless of protein coating. These data provide guidance to rational design of bioinert, long-circulating nanoparticles. PMID:19394687

  18. Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance.

    PubMed

    Simberg, Dmitri; Park, Ji-Ho; Karmali, Priya P; Zhang, Wan-Ming; Merkulov, Sergei; McCrae, Keith; Bhatia, Sangeeta N; Sailor, Michael; Ruoslahti, Erkki

    2009-08-01

    In order to understand the role of plasma proteins in the rapid liver clearance of dextran-coated superparamagnetic iron oxide (SPIO) in vivo, we analyzed the full repertoire of SPIO-binding blood proteins using novel two-dimensional differential mass spectrometry approach. The identified proteins showed specificity for surface domains of the nanoparticles: mannan-binding lectins bound to the dextran coating, histidine-rich glycoprotein and kininogen bound to the iron oxide part, and the complement lectin and contact clotting factors were secondary binders. Nanoparticle clearance studies in knockout mice suggested that these proteins, as well as several previously identified opsonins, do not play a significant role in the SPIO clearance. However, both the dextran coat and the iron oxide core remained accessible to specific probes after incubation of SPIO in plasma, suggesting that the nanoparticle surface could be available for recognition by macrophages, regardless of protein coating. These data provide guidance to rational design of bioinert, long-circulating nanoparticles.

  19. Effects of sodium benzoate, a widely used food preservative, on glucose homeostasis and metabolic profiles in humans.

    PubMed

    Lennerz, Belinda S; Vafai, Scott B; Delaney, Nigel F; Clish, Clary B; Deik, Amy A; Pierce, Kerry A; Ludwig, David S; Mootha, Vamsi K

    2015-01-01

    Sodium benzoate is a widely used preservative found in many foods and soft drinks. It is metabolized within mitochondria to produce hippurate, which is then cleared by the kidneys. We previously reported that ingestion of sodium benzoate at the generally regarded as safe (GRAS) dose leads to a robust excursion in the plasma hippurate level [1]. Since previous reports demonstrated adverse effects of benzoate and hippurate on glucose homeostasis in cells and in animal models, we hypothesized that benzoate might represent a widespread and underappreciated diabetogenic dietary exposure in humans. Here, we evaluated whether acute exposure to GRAS levels of sodium benzoate alters insulin and glucose homeostasis through a randomized, controlled, cross-over study of 14 overweight subjects. Serial blood samples were collected following an oral glucose challenge, in the presence or absence of sodium benzoate. Outcome measurements included glucose, insulin, glucagon, as well as temporal mass spectrometry-based metabolic profiles. We did not find a statistically significant effect of an acute oral exposure to sodium benzoate on glucose homeostasis. Of the 146 metabolites targeted, four changed significantly in response to benzoate, including the expected rise in benzoate and hippurate. In addition, anthranilic acid, a tryptophan metabolite, exhibited a robust rise, while acetylglycine dropped. Although our study shows that GRAS doses of benzoate do not have an acute, adverse effect on glucose homeostasis, future studies will be necessary to explore the metabolic impact of chronic benzoate exposure. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Effects of sodium benzoate, a widely used food preservative, on glucose homeostasis and metabolic profiles in humans

    PubMed Central

    Lennerz, Belinda; Vafai, Scott B.; Delaney, Nigel F.; Clish, Clary B.; Deik, Amy A.; Pierce, Kerry A.; Ludwig, David S.; Mootha, Vamsi K.

    2014-01-01

    Sodium benzoate is a widely used preservative found in many foods and soft drinks. It is metabolized within mitochondria to produce hippurate, which is then cleared by the kidneys. We previously reported that ingestion of sodium benzoate at the generally regarded as safe (GRAS) dose leads to a robust excursion in the plasma hippurate level [1]. Since previous reports demonstrated adverse effects of benzoate and hippurate on glucose homeostasis in cells and in animal models, we hypothesized that benzoate might represent a widespread and underappreciated diabetogenic dietary exposure in humans. Here, we evaluated whether acute exposure to GRAS levels of sodium benzoate alters insulin and glucose homeostasis through a randomized, controlled, cross-over study of 14 overweight subjects. Serial blood samples were collected following an oral glucose challenge, in the presence or absence of sodium benzoate. Outcome measurements included glucose, insulin, glucagon, as well as temporal mass spectrometry-based metabolic profiles. We did not find a statistically significant effect of an acute oral exposure to sodium benzoate on glucose homeostasis. Of the 146 metabolites targeted, four changed significantly in response to benzoate, including the expected rise in benzoate and hippurate. In addition, anthranilic acid, a tryptophan metabolite, exhibited a robust rise, while acetylglycine dropped. Although our study shows that GRAS doses of benzoate do not have an acute, adverse effect on glucose homeostasis, future studies will be necessary to explore the metabolic impact of chronic benzoate exposure. PMID:25497115

  1. Dextran templating for the synthesis of metallic and metal oxide sponges

    NASA Astrophysics Data System (ADS)

    Walsh, Dominic; Arcelli, Laura; Ikoma, Toshiyuki; Tanaka, Junzo; Mann, Stephen

    2003-06-01

    Silver or gold-containing porous frameworks have been used extensively in catalysis, electrochemistry, heat dissipation and biofiltration. These materials are often prepared by thermal reduction of metal-ion-impregnated porous insoluble supports (such as alumina and pumice), and have surface areas of about 1 m2 g-1, which is typically higher than that obtained for pure metal powders or foils prepared electrolytically or by infiltration and thermal decomposition of insoluble cellulose supports. Starch gels have been used in association with zeolite nanoparticles to produce porous inorganic materials with structural hierarchy, but the use of soft sacrificial templates in the synthesis of metallic sponges has not been investigated. Here we demonstrate that self-supporting macroporous frameworks of silver, gold and copper oxide, as well as composites of silver/copper oxide or silver/titania can be routinely prepared by heating metal-salt-containing pastes of the polysaccharide, dextran, to temperatures between 500 and 900 °C. Magnetic sponges were similarly prepared by replacing the metal salt precursor with preformed iron oxide (magnetite) nanoparticles. The use of dextran as a sacrificial template for the fabrication of metallic and metal oxide sponges should have significant benefits over existing technologies because the method is facile, inexpensive, environmentally benign, and amenable to scale-up and processing.

  2. Acute Toxicity of Sodium Fluorescein to Ashy Pebblesnails Fluminicola fuscus

    USGS Publications Warehouse

    Stockton, Kelly A.; Moffitt, Christine M.; Blew, David L.; Farmer, C. Neil

    2011-01-01

    Water resource agencies and groundwater scientists use fluorescein dyes to trace ground water flows that supply surface waters that may contain threatened or endangered mollusk species. Since little is known of the toxicity of sodium fluorescein to mollusks, we tested the toxicity of sodium fluorescein to the ashy pebblesnail Fluminicola fuscus. The pebblesnail was selected as a surrogate test species for the threatened Bliss Rapid snail Taylorcocha serpenticola that is endemic to the Snake River and its tributaries in the Hagerman Valley, Idaho. In laboratory tests, we expose replicated groups of snails to a series of concentrations of fluorescein in a static 24 h exposure at 15 degrees C. Following the exposure, we removed snails, rinsed them, and allowed a 48 h recovery in clean water before recording mortality. We estimated 377 mg/L as the median lethal dose. Mortality to snails occurred at concentrations well above those expected in test wells during the monitoring efforts.

  3. Efficacy and safety of i.v. sodium benzoate in urea cycle disorders: a multicentre retrospective study.

    PubMed

    Husson, Marie-Caroline; Schiff, Manuel; Fouilhoux, Alain; Cano, Aline; Dobbelaere, Dries; Brassier, Anais; Mention, Karine; Arnoux, Jean-Baptiste; Feillet, François; Chabrol, Brigitte; Guffon, Nathalie; Elie, Caroline; de Lonlay, Pascale

    2016-09-23

    The efficacy and safety of intra-venous (i.v.) sodium benzoate for treating acute episodes of hyperammonemia in urea cycle enzyme disorders (UCD) is well known. However, published data do not provide a clear picture of the benefits and risks of this drug. We report a retrospective multicentre study on the use of i.v. sodium benzoate in patients treated for UCD between 2000 and 2010 in the 6 French reference centres for metabolic diseases. Sixty-one patients with UCDs - 22 ornithine transcarbamylase (20 confirmed, 2 suspected), 18 arginino-succinate synthetase, 15 carbamoyl phosphate synthetase, 3 arginosuccinate lyase, 1 arginase deficiency, 1 N-acetylglutamate synthetase, 1 HHH syndrome - required i.v. sodium benzoate over the course of 95 acute episodes (NH3 > 100 μmol/L or high-risk situations, i.e., gastroenteritis, surgery). Forty out of 61 patients experienced only one episode of decompensation (neonatal coma, 68.6 %). The most frequent cause of late decompensation was infection (55.5 %). A loading dose of i.v. sodium benzoate (median 250 mg/kg over 2 h) was administered for 41/95 acute episodes. The median maintenance dose was 246.1 mg/kg/day, administered via peripheral venous infusion in all cases except one via a central line. The total median duration of i.v. sodium benzoate treatment per episode was 2 days (0-13 days). The median durations of hospitalization in intensive care and metabolic units were 4 days (0-17 days) and 10 days (0-70 days), respectively. Eight patients died during the neonatal coma (n = 6) or surgery (n = 2). The median plasma ammonium level before treatment was 245.5 μmol/L (20.0-2274.0 μmol/L); it decreased to 40.0 μmol/L in patients who were alive (13.0-181.0 μmol/L) at the end of treatment with i.v. sodium benzoate. A decrease in ammonium level to ≤ 100 μmol/L was obtained in 92.8 % of episodes (64/69 of the episodes recorded for the 53 surviving patients). Five patients required another

  4. 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.

  5. Optimization of peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) for the detection of bacteria: The effect of pH, dextran sulfate and probe concentration.

    PubMed

    Rocha, Rui; Santos, Rita S; Madureira, Pedro; Almeida, Carina; Azevedo, Nuno F

    2016-05-20

    Fluorescence in situ hybridization (FISH) is a molecular technique widely used for the detection and characterization of microbial populations. FISH is affected by a wide variety of abiotic and biotic variables and the way they interact with each other. This is translated into a wide variability of FISH procedures found in the literature. The aim of this work is to systematically study the effects of pH, dextran sulfate and probe concentration in the FISH protocol, using a general peptide nucleic acid (PNA) probe for the Eubacteria domain. For this, response surface methodology was used to optimize these 3 PNA-FISH parameters for Gram-negative (Escherichia coli and Pseudomonas fluorescens) and Gram-positive species (Listeria innocua, Staphylococcus epidermidis and Bacillus cereus). The obtained results show that a probe concentration higher than 300nM is favorable for both groups. Interestingly, a clear distinction between the two groups regarding the optimal pH and dextran sulfate concentration was found: a high pH (approx. 10), combined with lower dextran sulfate concentration (approx. 2% [w/v]) for Gram-negative species and near-neutral pH (approx. 8), together with higher dextran sulfate concentrations (approx. 10% [w/v]) for Gram-positive species. This behavior seems to result from an interplay between pH and dextran sulfate and their ability to influence probe concentration and diffusion towards the rRNA target. This study shows that, for an optimum hybridization protocol, dextran sulfate and pH should be adjusted according to the target bacteria. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Chemical Functionalization of Germanium with Dextran Brushes for Immobilization of Proteins Revealed by Attenuated Total Reflection Fourier Transform Infrared Difference Spectroscopy.

    PubMed

    Schartner, Jonas; Hoeck, Nina; Güldenhaupt, Jörn; Mavarani, Laven; Nabers, Andreas; Gerwert, Klaus; Kötting, Carsten

    2015-07-21

    Protein immobilization studied by attenuated total reflection Fourier transform infrared (ATR-FT-IR) difference spectroscopy is an emerging field enabling the study of proteins at atomic detail. Gold or glass surfaces are frequently used for protein immobilization. Here, we present an alternative method for protein immobilization on germanium. Because of its high refractive index and broad spectral window germanium is the best material for ATR-FT-IR spectroscopy of thin layers. So far, this technique was mainly used for protein monolayers, which lead to a limited signal-to-noise ratio. Further, undesired protein-protein interactions can occur in a dense layer. Here, the germanium surface was functionalized with thiols and stepwise a dextran brush was generated. Each step was monitored by ATR-FT-IR spectroscopy. We compared a 70 kDa dextran with a 500 kDa dextran regarding the binding properties. All surfaces were characterized by atomic force microscopy, revealing thicknesses between 40 and 110 nm. To analyze the capability of our system we utilized N-Ras on mono-NTA (nitrilotriacetic acid) functionalized dextran, and the amount of immobilized Ras corresponded to several monolayers. The protein stability and loading capacity was further improved by means of tris-NTA for immobilization. Small-molecule-induced changes were revealed with an over 3 times higher signal-to-noise ratio compared to monolayers. This improvement may allow the observation of very small and so far hidden changes in proteins upon stimulus. Furthermore, we immobilized green fluorescent protein (GFP) and mCherry simultaneously enabling an analysis of the surface by fluorescence microscopy. The absence of a Förster resonance energy transfer (FRET) signal demonstrated a large protein-protein distance, indicating an even distribution of the protein within the dextran.

  7. Effect of acarbose on acute acidosis.

    PubMed

    McLaughlin, C L; Thompson, A; Greenwood, K; Sherington, J; Bruce, C

    2009-06-01

    A challenge model was used to evaluate a new approach to controlling acute acidosis. Acute acidosis reduces performance in both dairy and beef cattle and most often occurs as a consequence of ingestion of large amounts of readily fermentable starch, resulting in increased production of volatile fatty acids (VFA) and lactic acid and a reduction in ruminal pH. Acarbose is an alpha-amylase and glucosidase inhibitor that slows the rate of degradation of starch to glucose, thereby reducing the rate of VFA production and maintaining rumen pH at a more stable level. It is commercially available (Glucobay, Bayer, Wuppertal, Germany) and indicated for the control of blood glucose in diabetic patients. The ability of acarbose to reduce the incidence of acidosis and the comparative efficacies of acarbose, sodium bicarbonate, and monensin were tested in 3 acute acidosis challenge experiments in cattle. Rumen-cannulated Holstein steers were challenged with a mixture of 48.4% cornstarch, 48.4% ground corn, 2.1% sodium caseinate, and 1.1% urea with or without test substance. The challenge was administered at a rate of 12.5 g/kg of body weight (BW) as a slurry through the cannula directly into the rumen. Ruminal pH was monitored at 10-min intervals throughout the study. Animals were removed from study and rumen contents replaced if they exhibited acute acidosis as defined as pH <4.5. If acidosis was not observed within 24 h, animals were subjected to a second challenge. Ruminal fluid samples were taken for measurement of VFA and lactate concentrations at various intervals after the challenge. In experiment 1, the carbohydrate challenge induced acidosis in 4 of 4 control animals and 0 of 4 animals treated with 2.14 or 21.4 mg of acarbose/kg of BW in the challenge based on the criterion of pH <4.5. In experiment 2, the carbohydrate challenge induced acidosis in 4 of 7 control animals and 1 of 7 animals when 1.07 mg of acarbose/kg of BW was included in the challenge. In experiment 3

  8. Toxicological evaluation of 6'-sialyllactose (6'-SL) sodium salt.

    PubMed

    Gurung, Rit Bahadur; Kim, Dae Hee; Kim, Lila; Lee, Albert W; Wang, Zhenhua; Gao, Yonglin

    2018-06-01

    We performed a series of toxicity studies on the safety of 6'-sialyllactose (6'-SL) sodium salt as a food ingredient. 6'-SL sodium salt, up to a maximum dose of 5000 μg/plate, did not increase the number of revertant colonies in five strains of Salmonella typhimurium in the presence or absence of S9 metabolic activation. A chromosomal aberration assay (using Chinese hamster lung cells) found no clastogenic effects at any concentration of 6'-SL sodium salt in the presence or absence of S9 metabolic activation. An in vivo bone marrow micronucleus test in Kunming mice showed no clastogenic activities with 6'-SL sodium salt doses up to 2000 mg/kg body weight (bw). In an acute toxicity study, the mean lethal dose of 6'-SL sodium salt was greater than 20 g/kg bw in rats. In a 13-week subchronic toxicity investigation, no effects were found at doses up to 5.0 g/kg bw of 6'-SL sodium salt in food consumption, body weight, clinical signs, blood biochemistry and hematology, urinalysis, or ophthalmic and histological macroscopic examination of organs. The no-observed-adverse-effect level (NOAEL) was 5.0 g/kg bw/day in rats. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Effect of DEXTRAN-graft-POLYACRYLAMIDE Internal Structure on Flocculation Process Parameters

    NASA Astrophysics Data System (ADS)

    Bezugla, T.; Kutsevol, N.; Shyichuk, A.; Ziolkowska, D.

    2008-08-01

    Dextran-graft-Polyacrylamide copolymers (D-g-PAA) of brush-like architecture were tested as flocculation aids in the model kaolin suspensions. Due to expanded conformation the D-g-PAA copolymers are more effective flocculants than individual PAA with close molecular mass. The internal structure of D-g-PAA copolymers which is determined by number and length of grafted PAA chains, the distance between grafts, etc., has the significant influence on flocculation behavior of such polymers.

  10. Calciuric effects of short-term dietary loading of protein, sodium chloride and potassium citrate in prepubescent girls.

    PubMed

    Duff, T L; Whiting, S J

    1998-04-01

    Studies using adult human subjects indicate that dietary protein and sodium chloride have negative effects on the retention of calcium by increasing urinary calcium excretion, while alkaline potassium improves calcium retention along with decreasing urinary calcium losses. This study investigated the effect of these dietary factors on acute urinary calcium excretion in 14 prepubescent girls age 6.7 to 10.0 years. Subjects provided a fasting urine sample then consumed a meal containing one of five treatments: moderate protein (MP) providing 11.8 g protein, moderate protein plus 26 mmol sodium chloride (MP+Na), high protein (HP) providing 28.8 g protein, high protein plus 26 mmol sodium chloride (HP+Na), or high protein plus 32 mmol potassium as tripotassium citrate (HP+K). Urine was collected at 1.5 and 3.0 hours after the meal. Supplemental protein was given as 80:20 casein:lactalbumin. Test meals were isocaloric, and unless intentionally altered, components of interest except phosphate were equal between treatments. Each subject completed all five treatments. Urinary calcium excretion rose after the meal, peaking at 1.5 hours. There were no significant differences in calcium excretion between treatments at any time point. The high protein treatments did not result in a significant increase in either net acid or sulfate excretion at 1.5 hours compared to moderate protein. Dietary sodium chloride had no effect on urinary sodium or calcium excretion over the 3 hours. After the potassium treatment, sodium excretion increased (p< or =0.002) and net acid excretion decreased (p<0.001) compared to other treatments at 1.5 hours. In children, a simultaneous increase in protein and phosphorus due to increased milk protein intake did not increase acute urinary calcium excretion. An effect of dietary sodium chloride on acute urinary calcium excretion was not observed. Both these findings were similar to those of adult studies previously conducted in the same laboratory using

  11. Feedforward activation of endothelial ENaC by high sodium

    PubMed Central

    Korte, Stefanie; Sträter, Alexandra S.; Drüppel, Verena; Oberleithner, Hans; Jeggle, Pia; Grossmann, Claudia; Fobker, Manfred; Nofer, Jerzy-Roch; Brand, Eva; Kusche-Vihrog, Kristina

    2014-01-01

    Kidney epithelial sodium channels (ENaCs) are known to be inactivated by high sodium concentrations (feedback inhibition). Recently, the endothelial sodium channel (EnNaC) was identified to control the nanomechanical properties of the endothelium. EnNaC-dependent endothelial stiffening reduces the release of nitric oxide, the hallmark of endothelial dysfunction. To study the regulatory impact of sodium on EnNaC, endothelial cells (EA.hy926 and ex vivo mouse endothelium) were incubated in aldosterone-free solutions containing either low (130 mM) or high (150 mM) sodium concentrations. By applying atomic force microscopy-based nanoindentation, an unexpected positive correlation between increasing sodium concentrations and cortical endothelial stiffness was observed, which can be attributed to functional EnNaC. In particular, an acute rise in sodium concentration (+20 mM) was sufficient to increase EnNaC membrane abundance by 90% and stiffening of the endothelial cortex by 18%. Despite the absence of exogenous aldosterone, these effects were prevented by the aldosterone synthase inhibitor FAD286 (100 nM) or the mineralocorticoid receptor (MR)-antagonist spironolactone (100 nM), indicating endogenous aldosterone synthesis and MR-dependent signaling. Interestingly, in the presence of high-sodium concentrations, FAD286 increased the transcription of the MR by 69%. Taken together, a novel feedforward activation of EnNaC by sodium is proposed that contrasts ENaC feedback inhibition in kidney.—Korte, S., Sträter, A. S., Drüppel, V., Oberleithner, H., Jeggle, P., Grossmann, C., Fobker, M., Nofer, J.-R., Brand, E., Kusche-Vihrog, K. Feedforward activation of endothelial ENaC by high sodium. PMID:24868010

  12. Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial.

    PubMed

    Malamiri, Reza Azizi; Ghaempanah, Mahdieh; Khosroshahi, Nahid; Nikkhah, Ali; Bavarian, Behrouz; Ashrafi, Mahmoud Reza

    2012-09-01

    Status epilepticus and acute prolonged seizures are the most commonly occurring neurological emergencies in children. Such events have high morbidity and mortality rates along with poor long-term outcomes, depending on their duration and causes. Therefore, such seizures warrant urgent treatment using appropriate doses of anticonvulsants. Benzodiazepines, phenobarbital, and phenytoin are the most commonly used anticonvulsants for controlling status epilepticus and acute prolonged seizures. However, these medications have several well-known adverse effects. Previous studies on both adults and children have shown the efficacy and safety of rapid infusion of valproate in controlling status epilepticus. However, few well-designed randomised trials have been carried out in children, and there remains a paucity of data regarding intravenous sodium valproate use in children. Therefore, our aim was to compare the efficacy and safety of rapid loading of valproate with those of intravenous phenobarbital in children with status epilepticus and acute prolonged seizures. Sixty children (30 in each group) with convulsive status epilepticus and acute prolonged seizures were enrolled and randomly assigned to receive either valproate or phenobarbital. The main outcome variable was termination of all convulsive activity within 20 min of starting anticonvulsant infusion. Intravenous rapid loading of valproate was successful in seizure termination in (27/30, 90%) of patients compared to phenobarbital (23/30, 77%) (p = 0.189). Clinically significant adverse effects occurred in 74% patients of the phenobarbital group and 24% patients of the valproate group (p < 0.001). In conclusion, rapid loading of valproate is effective and safe in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children. Intravenous valproate should be considered as a suitable choice for terminating status epilepticus and acute prolonged seizures in children. Copyright

  13. Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlation with salt sensitivity in normal subjects.

    PubMed

    ter Maaten, J C; Bakker, S J; Serné, E H; ter Wee, P M; Donker, A J; Gans, R O

    1999-10-01

    Insulin induces sodium retention by increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects could link insulin resistance to blood-pressure elevation and salt sensitivity. We assessed the relationship between the effects of sequential physiological and supraphysiological insulin dosages (50 and 150 mU/kg/h) on renal sodium handling, and insulin sensitivity and salt sensitivity using the euglycaemic clamp technique and clearances of [131I]hippuran, [125I]iothalamate, sodium, and lithium in 20 normal subjects displaying a wide range of insulin sensitivity. Time-control experiments were performed in the same subjects. Salt sensitivity was determined using a diet method. During the successive insulin infusions, GFR increased by 5.9% (P = 0.003) and 10.9% (P<0.001), while fractional sodium excretion decreased by 34 and 50% (both P<0.001). Distal tubular sodium reabsorption increased and proximal tubular sodium reabsorption decreased. Insulin sensitivity correlated with changes in GFR during physiological (r = 0.60, P = 0.005) and supraphysiological (r = 0.58, P = 0.007) hyperinsulinaemia, but not with changes in proximal tubular sodium reabsorption. Salt sensitivity correlated with changes in proximal tubular sodium reabsorption (r = 0.49, P = 0.028), but not in GFR, during physiological hyperinsulinaemia. Neither insulin sensitivity or salt sensitivity correlated with changes in overall fractional sodium excretion. Insulin sensitivity and salt sensitivity correlate with changes in different elements of renal sodium handling, but not with overall sodium excretion, during insulin infusion. The relevance for blood pressure regulation remains to be proved.

  14. Edelman's equation is valid in acute hyponatremia in a porcine model: plasma sodium concentration is determined by external balances of water and cations.

    PubMed

    Overgaard-Steensen, Christian; Larsson, Anders; Bluhme, Henrik; Tønnesen, Else; Frøkiaer, Jørgen; Ring, Troels

    2010-01-01

    Acute hyponatremia is a serious condition, which poses major challenges. Of particular importance is what determines plasma sodium concentration ([Na(+)]). Edelman introduced an explicit model to describe plasma [Na(+)] in a population as [Na(+)] = alpha.(exchangeable Na(+) + exchangeable K(+))/(total body water) - beta. Evidence for the clinical utility of the model in the individual and in acute hyponatremia is sparse. We, therefore, investigated how the measured plasma [Na(+)] could be predicted in a porcine model of hyponatremia. Plasma [Na(+)] was estimated from in vivo-determined balances of water, Na(+), and K(+), according to Edelman's equation. Acute hyponatremia was induced with desmopressin acetate and infusion of a 2.5% glucose solution in anesthetized pigs. During 480 min, plasma [Na(+)] and osmolality were reduced from 136 (SD 2) to 120 mmol/l (SD 3) and from 284 (SD 4) to 252 mosmol/kgH(2)O (SD 5), respectively. The following interpretations were made. First, Edelman's model, which, besides dilution, takes into account Na(+) and K(+), fits plasma [Na(+)] significantly better than dilution alone. Second, a common value of alpha = 1.33 (SD 0.08) and beta = -13.04 mmol/l (SD 7.68) for all pigs explains well the plasma [Na(+)] in the individual animal. Third, measured exchangeable Na(+) and calculated exchangeable Na(+) + K(+) per weight in the pigs are close to Edelman's findings in humans, whereby the methods are cross-validated. In conclusion, plasma [Na(+)] can be explained in the individual animal by external balances, according to Edelman's construct in acute hyponatremia.

  15. 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

  16. Effect of surface charge on the colloidal stability and in vitro uptake of carboxymethyl dextran-coated iron oxide nanoparticles

    PubMed Central

    Ayala, Vanessa; Herrera, Adriana P.; Latorre-Esteves, Magda; Torres-Lugo, Madeline

    2013-01-01

    Nanoparticle physicochemical properties such as surface charge are considered to play an important role in cellular uptake and particle–cell interactions. In order to systematically evaluate the role of surface charge on the uptake of iron oxide nanoparticles, we prepared carboxymethyl-substituted dextrans with different degrees of substitution, ranging from 38 to 5 groups per chain, and reacted them using carbodiimide chemistry with amine–silane-coated iron oxide nanoparticles with narrow size distributions in the range of 33–45 nm. Surface charge of carboxymethyl-substituted dextran-coated nano-particles ranged from −50 to 5 mV as determined by zeta potential measurements, and was dependent on the number of carboxymethyl groups incorporated in the dextran chains. Nanoparticles were incubated with CaCo-2 human colon cancer cells. Nanoparticle–cell interactions were observed by confocal laser scanning microscopy and uptake was quantified by elemental analysis using inductively coupled plasma mass spectroscopy. Mechanisms of internalization were inferred using pharmacological inhibitors for fluid-phase, clathrin-mediated, and caveola-mediated endocytosis. Results showed increased uptake for nanoparticles with greater negative charge. Internalization patterns suggest that uptake of the most negatively charged particles occurs via non-specific interactions. PMID:24470787

  17. TGF-β directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury

    PubMed Central

    Peters, Dorothea M.; Vadász, István; Wujak, Łukasz; Wygrecka, Małgorzata; Olschewski, Andrea; Becker, Christin; Herold, Susanne; Papp, Rita; Mayer, Konstantin; Rummel, Sebastian; Brandes, Ralph P.; Günther, Andreas; Waldegger, Siegfried; Eickelberg, Oliver; Seeger, Werner; Morty, Rory E.

    2014-01-01

    TGF-β is a pathogenic factor in patients with acute respiratory distress syndrome (ARDS), a condition characterized by alveolar edema. A unique TGF-β pathway is described, which rapidly promoted internalization of the αβγ epithelial sodium channel (ENaC) complex from the alveolar epithelial cell surface, leading to persistence of pulmonary edema. TGF-β applied to the alveolar airspaces of live rabbits or isolated rabbit lungs blocked sodium transport and caused fluid retention, which—together with patch-clamp and flow cytometry studies—identified ENaC as the target of TGF-β. TGF-β rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4-phosphate 5-kinase 1α, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving internalization of βENaC, the subunit responsible for cell-surface stability of the αβγENaC complex. ENaC internalization was dependent on oxidation of βENaC Cys43. Treatment of alveolar epithelial cells with bronchoalveolar lavage fluids from ARDS patients drove βENaC internalization, which was inhibited by a TGF-β neutralizing antibody and a Tgfbr1 inhibitor. Pharmacological inhibition of TGF-β signaling in vivo in mice, and genetic ablation of the nox4 gene in mice, protected against perturbed lung fluid balance in a bleomycin model of lung injury, highlighting a role for both proximal and distal components of this unique ENaC regulatory pathway in lung fluid balance. These data describe a unique TGF-β–dependent mechanism that regulates ion and fluid transport in the lung, which is not only relevant to the pathological mechanisms of ARDS, but might also represent a physiological means of acutely regulating ENaC activity in the lung and other organs. PMID:24324142

  18. TGF-β directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury.

    PubMed

    Peters, Dorothea M; Vadász, István; Wujak, Lukasz; Wygrecka, Malgorzata; Olschewski, Andrea; Becker, Christin; Herold, Susanne; Papp, Rita; Mayer, Konstantin; Rummel, Sebastian; Brandes, Ralph P; Günther, Andreas; Waldegger, Siegfried; Eickelberg, Oliver; Seeger, Werner; Morty, Rory E

    2014-01-21

    TGF-β is a pathogenic factor in patients with acute respiratory distress syndrome (ARDS), a condition characterized by alveolar edema. A unique TGF-β pathway is described, which rapidly promoted internalization of the αβγ epithelial sodium channel (ENaC) complex from the alveolar epithelial cell surface, leading to persistence of pulmonary edema. TGF-β applied to the alveolar airspaces of live rabbits or isolated rabbit lungs blocked sodium transport and caused fluid retention, which--together with patch-clamp and flow cytometry studies--identified ENaC as the target of TGF-β. TGF-β rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4-phosphate 5-kinase 1α, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving internalization of βENaC, the subunit responsible for cell-surface stability of the αβγENaC complex. ENaC internalization was dependent on oxidation of βENaC Cys(43). Treatment of alveolar epithelial cells with bronchoalveolar lavage fluids from ARDS patients drove βENaC internalization, which was inhibited by a TGF-β neutralizing antibody and a Tgfbr1 inhibitor. Pharmacological inhibition of TGF-β signaling in vivo in mice, and genetic ablation of the nox4 gene in mice, protected against perturbed lung fluid balance in a bleomycin model of lung injury, highlighting a role for both proximal and distal components of this unique ENaC regulatory pathway in lung fluid balance. These data describe a unique TGF-β-dependent mechanism that regulates ion and fluid transport in the lung, which is not only relevant to the pathological mechanisms of ARDS, but might also represent a physiological means of acutely regulating ENaC activity in the lung and other organs.

  19. Sodium polystyrene sulfonate for the treatment of acute hyperkalemia: a retrospective study.

    PubMed

    Hagan, Amanda E; Farrington, Crystal A; Wall, Geoffrey C; Belz, Mark M

    2016-01-01

    Hyperkalemia is a common problem in hospitalized patients, especially those with underlying chronic kidney disease, but evidence-based guidelines for its treatment are lacking. Sodium polystyrene sulfonate (SPS), a cation exchange resin first approved by the FDA for the treatment of hyperkalemia in 1958, is frequently used alone or in conjunction with other medical therapies to lower serum potassium. Recently, the safety and efficacy of SPS have come into question based on multiple reported cases of bowel necrosis associated with SPS administration. The primary objective of this study was to evaluate the use of SPS for the treatment of hyperkalemia, at a large tertiary community teaching hospital, to determine its effectiveness and the incidence of related adverse side effects. A retrospective chart review was performed on all adult inpatients receiving single-dose SPS at a 466-bed tertiary community teaching hospital over a 3-year period. 501 patients received SPS for the treatment of hyperkalemia during their index hospital stay. Serum potassium levels decreased by 0.93 mEq/L on average at first recheck after SPS administration, with or without additional medical treatments. Our study identified 10 cases of hypernatremia (greater than 145 mEq/L), 31 cases of hypokalemia (less than 3.5 mEq/L), and 2 cases of bowel necrosis related to the administration of SPS. Our results suggest a serum potassium reduction of less than 1 mEq/L after administration of SPS for the treatment of acute hyperkalemia. Additionally, this study offers some evidence that the use of SPS may be associated with harm. We further note the need for standardized guidelines for the treatment of hyperkalemia at our institution.

  20. Rapid Size- Controlled Synthesis of Dextran-Coated, Copper-Doped Iron Oxide Nanoparticles

    NASA Astrophysics Data System (ADS)

    Wong, Ray M.

    2011-12-01

    Development of dual modality probes enabled for magnetic resonance imaging (MRI) and positron emission tomography (PET) has been on the rise in recent years due to the potential for these probes to facilitate combining the complementary high resolution of MRI and the high sensitivity of PET. The efficient synthesis of multimodal probes that include the radiolabels for PET can be hindered due to prolonged reaction times during radioisotope incorporation, and the resulting decay of the radiolabel. Along with a time-efficient synthesis, one also needs an optimal synthesis that yields products in a desirable size range (between 20-100 nm) to increase blood retention time. In this work, we describe a novel, rapid, microwave-based synthesis of dextran-coated iron oxide nanoparticles doped with copper (DIO/Cu). Traditional methods for synthesizing dextran-coated iron oxide particles require refluxing for 2 hours and result in approximately 50 nm particles. We demonstrate that microwave synthesis can produce 50 nm nanoparticles in 5 minutes of heating. We discuss the various parameters used in the microwave synthesis protocol to vary the size distribution of DIO/Cu, and demonstrate the successful incorporation of copper into these particles with the aim of future use for rapid 64Cu incorporation.