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Sample records for acute dextran sodium

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

    PubMed

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

    2016-01-01

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

  2. 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

  3. Protein Kinase D2 Protects against Acute Colitis Induced by Dextran Sulfate Sodium in Mice

    PubMed Central

    Xiong, Jing; Zhou, Ming-feng; Wang, Ya-dong; Chen, Li-ping; Xu, Wan-fu; Wang, Yao-dong; Deng, Fan; Liu, Si-de

    2016-01-01

    Inflammatory bowel disease is characterized by dysregulation of the mucosal immune system resulting from impaired intestinal epithelial barrier function. Protein kinase D2 has been implicated in the regulation of immune responses. The present study was to define PKD2 might affect murine colitis. Colitis was induced in wild-type mice (PKD2WT/WT) and PKD2 catalytic activity deficient mice (PKD2SSAA/SSAA) with dextran sulfate sodium. PKD2SSAA-knockin mice displayed catalytic activity deficiency and increased susceptibility to DSS-induced colitis with enhanced weight loss, colonic inflammation compared with PKD2WT/WT mice. Furthermore, crucial inflammatory cytokines mRNA levels in PKD2SSAA-knockin mice were higher than controls accompanied with down-regulation of ZO-1, MUC2 and intestinal barrier dysfunction. However, there were no differences in the proliferation or apoptosis of intestinal epithelial cells in PKD2SSAA-knockin mice compared with wild-type controls. In addition, PKD2 expression was repressed in patients with IBD compared with healthy controls. These studies suggested that activation of PKD2 in the colonic epithelium microenvironment may contribute to protect against DSS-induced colitis through regulation of intestinal mucosal immunity and barrier function. PMID:27659202

  4. Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium.

    PubMed

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

    2015-08-01

    The renin angiotensin system (RAS) is essential for the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Recent studies have demonstrated a locally expressed RAS in various tissues of mammals, which is having pathophysiological roles in those organ system. Interestingly, local RAS has important role during the inflammatory bowel disease pathogenesis. Further to delineate its role and also to identify the potential effects of telmisartan, an angiotensin receptor blocker, we have used a mouse model of acute colitis induced by dextran sulphate sodium. We have used 0.01 and 5mg/kg body weight doses of telmisartan and administered as enema to facilitate the on-site action and to reduce the systemic adverse effects. Telmisartan high dose treatment significantly reduced the disease activity index score when compared with the colitis control mice. In addition, oxidative stress and endoplasmic reticulum stress markers expression were also significantly reduced when compared with the colitis control mice. Subsequent experiments were carried out to investigate some of the mechanisms underlying its anti-inflammatory effects and identified that the mRNA levels of pro-inflammatory cytokines such as tumour necrosis factor α, interleukin 1β, interleukin 6 and monocyte chemoattractant protein 1 as well as cellular DNA damage were significantly suppressed when compared with the colitis control mice. Similarly the apoptosis marker proteins such as cleaved caspase 3 and 7 levels were down-regulated and anti-apoptotic protein Bcl2 level was significantly upregulated by telmisartan treatment. These results indicate that blockade of RAS by telmisartan can be an effective therapeutic option against acute colitis.

  5. Protective role of G-CSF in dextran sulfate sodium-induced acute colitis through generating gut-homing macrophages.

    PubMed

    Meshkibaf, Shahab; Martins, Andrew J; Henry, Garth T; Kim, Sung Ouk

    2016-02-01

    Granulocyte colony-stimulating factor (G-CSF) is a pleiotropic cytokine best known for its role in promoting the generation and function of neutrophils. G-CSF is also found to be involved in macrophage generation and immune regulation; however, its in vivo role in immune homeostasis is largely unknown. Here, we examined the role of G-CSF in dextran sulfate sodium (DSS)-induced acute colitis using G-CSF receptor-deficient (G-CSFR(-/-)) mice. Mice were administered with 1.5% DSS in drinking water for 5days, and the severity of colitis was measured for the next 5days. GCSFR(-/-) mice were more susceptible to DSS-induced colitis than G-CSFR(+/+) or G-CSFR(-/+) mice. G-CSFR(-/-) mice harbored less F4/80(+) macrophages, but a similar number of neutrophils, in the intestine. In vitro, bone marrow-derived macrophages prepared in the presence of both G-CSF and macrophage colony-stimulating factor (M-CSF) (G-BMDM) expressed higher levels of regulatory macrophage markers such as programmed death ligand 2 (PDL2), CD71 and CD206, but not in arginase I, transforming growth factor (TGF)-β, Ym1 (chitinase-like 3) and FIZZ1 (found in inflammatory zone 1), and lower levels of inducible nitric oxide synthase (iNOS), CD80 and CD86 than bone marrow-derived macrophages prepared in the presence of M-CSF alone (BMDM), in response to interleukin (IL)-4/IL-13 and lipopolysaccharide (LPS)/interferon (IFN)-γ, respectively. Adoptive transfer of G-BMDM, but not BMDM, protected G-CSFR(-/-) mice from DSS-induced colitis, and suppressed expression of tumor necrosis factor (TNF)-α, IL-1β and iNOS in the intestine. These results suggest that G-CSF plays an important role in preventing colitis, likely through populating immune regulatory macrophages in the intestine.

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

    PubMed

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

    2015-01-01

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

  7. Effects of Dietary Glutamine on the Homeostasis of CD4+ T Cells in Mice with Dextran Sulfate Sodium-Induced Acute Colitis

    PubMed Central

    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. PMID:24416230

  8. Effect of Dextran 40 and aprotinin on experimental acute pancreatitis.

    PubMed

    Crocket, K V; Reising, J R; Wirman, J A; Gau, N; Joffe, S N

    1984-03-01

    This study examines and compares the prophylactic role of aprotinin and Dextran 40 in acute pancreatitis. Experimental acute pancreatitis was induced in 70 male Wistar rats using the closed-duodenal-loop technique. The rats were randomly divided into four groups; sham operation, untreated acute pancreatitis, and therapy with aprotinin or Dextran 40. Samples of blood and urine were collected at the beginning and at the end of the 24-hr period for measurement of amylase and creatinine which allowed calculation of the amylase-creatinine clearance ratio (ACCR). Mortality in the aprotinin group was the same as the untreated rats (20%). Dextran 40 therapy was associated with a lower mortality rate (6.7%). Light microscopic examination confirmed that the histologic changes of acute pancreatitis were less severe in both the aprotinin- and Dextran 40-treated rats. The ACCR was elevated after Dextran 40 therapy, which was due mainly to high urinary amylase levels. These results suggest that Dextran 40 may have a prophylactic role in acute experimental pancreatitis but again emphasizes the high false-positive rate of the ACCR determination. PMID:6199589

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-02-04

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

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

    PubMed

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

    2014-12-01

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

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

    PubMed Central

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

    2007-01-01

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

  13. Complement component 6 deficiency increases susceptibility to dextran sulfate sodium-induced murine colitis.

    PubMed

    Ding, Peipei; Li, Ling; Huang, Tianbao; Yang, Chaoqun; Xu, Enjie; Wang, Na; Zhang, Long; Gu, Hongyu; Yao, Xudong; Zhou, Xuhui; Hu, Weiguo

    2016-11-01

    As a potent effector of innate immunity, the complement system has been shown to be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the role of the membrane attack complex (MAC) in the development of IBD is still largely unknown. Here, we used C6-deficient mice in which MAC formation was blocked due to the absence of C6 to develop an acute colitis model by the administration of dextran sulfate sodium (DSS). The results showed that DSS-induced colitis was aggravated in C6-deficient mice compared with wild-type (WT) mice, as represented by the markedly greater weight loss, higher disease activity index (DAI), shortened colon length, more severe histological injury with increased epithelial ulcerations, and massively increased infiltration of leukocytes accompanied by much higher myeloperoxidase (MPO) levels in local inflammatory colonic sites. In addition, the DSS-induced colitis in C6-deficient mice could be significantly ameliorated by the exogenous C6 from WT sera. Furthermore, the significantly enhanced production of pro-inflammatory mediators, including IL-1β, IL-6, CXCL-1, CCL-3, TGF-β1 and IL-17F, was also observed in C6-deficient mice. Unexpectedly, the aggravated colitis in C6-deficient mice may be not due to the increase of lipopolysaccharide (LPS) levels in serum. Overall, we demonstrated that MAC exerts a protective role in acute colitis, strongly highlighting the host defense function of the complement system. PMID:27316715

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

    PubMed

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

    2015-05-01

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

  15. 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.

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

    PubMed Central

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

    2012-01-01

    One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms – bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression. PMID:22236013

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

    PubMed

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

    2012-02-01

    One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms - bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression.

  18. Inhibitory effect of the gallotannin corilagin on dextran sulfate sodium-induced murine ulcerative colitis.

    PubMed

    Xiao, Hai-Tao; Lin, Cheng-Yuan; Ho, Derek H H; Peng, Jiao; Chen, Yan; Tsang, Siu-Wai; Wong, Michael; Zhang, Xiao-Jun; Zhang, Man; Bian, Zhao-Xiang

    2013-11-22

    The therapeutic effect of corilagin (1) was evaluated in an acute colitis model induced by dextran sulfate sodium (DSS) in mice, and the mechanism of action was investigated in this study. Animals were challenged with 2% DSS drinking water for 5 consecutive days and then intraperitoneally treated with 1 (7.5, 15, and 30 mg/kg) daily for 7 days. It was found that 1 significantly decreased the disease activity index, inhibited the shortening of colon length, reduced colon tissue damage, and suppressed myeloperoxidase activity. Moreover, 1 greatly suppressed the secretion of TNF-α, IL-6, and IL-1β, inhibited the degradation of IκB α, and down-regulated expression of cleaved caspase-3 and cleaved caspase-9 in colon tissues of DSS-treated mice. These findings demonstrated that 1 exerts a protective effect on DSS-induced colitis, and its underlying mechanisms are associated with inhibition of the NF-κB pathway that mitigates colon inflammatory responses and apoptosis of intestinal epithelial cells. PMID:24200352

  19. Dietary Uptake of Wedelia chinensis Extract Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice

    PubMed Central

    Chen, Yung-Hsiang; Huang, Wen-Ching; Huang, Li-Ting; Lin, Wen-Ching; Arulselvan, Palanisamy; Liao, Jiunn-Wang; Lin, Shu-Hui; Hsiao, Pei-Wen; Kuo, Sheng-Chu; Yang, Ning-Sun

    2013-01-01

    Scope Traditional medicinal herbs are increasingly used as alternative therapies in patients with inflammatory diseases. Here we evaluated the effect of Wedelia chinensis, a medicinal herb commonly used in Asia, on the prevention of dextran sulfate sodium (DSS)-induced acute colitis in mice. General safety and the effect of different extraction methods on the bioactivity of W. chinensis were also explored. Methods and Results C57BL/6 mice were administrated hot water extract of fresh W. chinensis (WCHF) orally for one week followed by drinking water containing 2% DSS for nine days. WCHF significantly attenuated the symptoms of colitis including diarrhea, rectal bleeding and loss of body weight; it also reduced the shortening of colon length and histopathological damage caused by colonic inflammation. Among four W. chinensis extracts prepared using different extraction techniques, WCHF showed the highest anti-colitis efficacy. Analyses of specific T-cell regulatory cytokines (TNF-α, IL-4, IFN-γ, IL-17, TGF-β, IL-12) revealed that WCHF treatment can suppress the Th1 and Th17, but not Th2, responses in colon tissues and dendritic cells of DSS-induced colitis mice. A 28-day subacute toxicity study showed that daily oral administration of WCHF (100, 500, 1000 mg/kg body weight) was not toxic to mice. Conclusion Together, our findings suggest that specific extracts of W. chinensis have nutritional potential for future development into nutraceuticals or dietary supplements for treatment of inflammatory bowel disease. PMID:23734189

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

    PubMed Central

    Pandurangan, Ashok Kumar; Mohebali, Nooshin; Norhaizan, Mohd Esa; Looi, Chung Yeng

    2015-01-01

    Gallic acid (GA) is a polyhydroxy phenolic compound that has been detected in various natural products, such as green tea, strawberries, grapes, bananas, and many other fruits. In inflammatory bowel disease, inflammation is promoted by oxidative stress. GA is a strong antioxidant; thus, we evaluated the cytoprotective and anti-inflammatory role of GA in a dextran sulfate sodium (DSS)-induced mouse colitis model. Experimental acute colitis was induced in male BALB/c mice by administering 2.5% DSS in the drinking water for 7 days. The disease activity index; colon weight/length ratio; histopathological analysis; mRNA expressions of IL-21 and IL-23; and protein expression of nuclear erythroid 2-related factor 2 (Nrf2) were compared between the control and experimental mice. The colonic content of malondialdehyde and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity were examined as parameters of the redox state. We determined that GA significantly attenuated the disease activity index and colon shortening, and reduced the histopathological evidence of injury. GA also significantly (P<0.05) reduced the expressions of IL-21 and IL-23. Furthermore, GA activates/upregulates the expression of Nrf2 and its downstream targets, including UDP-GT and NQO1, in DSS-induced mice. The findings of this study demonstrate the protective effect of GA on experimental colitis, which is probably due to an antioxidant nature of GA. PMID:26251571

  1. Effects of orally administered bovine lactoperoxidase on dextran sulfate sodium-induced colitis in mice.

    PubMed

    Shin, Kouichirou; Horigome, Ayako; Yamauchi, Koji; Takase, Mitsunori; Yaeshima, Tomoko; Iwatsuki, Keiji

    2008-07-01

    The effect of lactoperoxidase (LPO) on dextran sulfate sodium-induced colitis was examined in mice. After 9 d of colitis induction, weight loss, colon shortening, and the histological score were significantly suppressed in mice orally administered LPO (62.5 mg/body/d) as compared to a group administered bovine serum albumin. These results suggest that LPO exhibits anti-inflammatory effects in the gastrointestinal tract.

  2. 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.

  3. Orally delivered β-glucans aggravate dextran sulfate sodium (DSS)-induced intestinal inflammation.

    PubMed

    Heinsbroek, Sigrid E M; Williams, David L; Welting, Olaf; Meijer, Sybren L; Gordon, Siamon; de Jonge, Wouter J

    2015-12-01

    β-Glucans have beneficial health effects due to their immune modulatory properties. Oral administration of β-glucans affects tumour growth, microbial infection, sepsis, and wound healing. We hypothesized that pre-treatment with orally delivered soluble and particulate β-glucans could ameliorate the development of aggravate dextran sulfate sodium (DSS) induced intestinal inflammation. To study this, mice were orally pre-treated with β-glucans for 14 days. We tested curdlan (a particulate β-(1,3)-glucan), glucan phosphate (a soluble β-(1,3)-glucan), and zymosan (a particle made from Saccharomyces cerevisiae, which contains around 55% β-glucans). Weight loss, colon weight, and feces score did not differ between β-glucan and vehicle treated groups. However, histology scores indicated that β-glucan-treated mice had increased inflammation at a microscopic level suggesting that β-glucan treatment worsened intestinal inflammation. Furthermore, curdlan and zymosan treatment led to increased colonic levels of inflammatory cytokines and chemokines, compared to vehicle. Glucan phosphate treatment did not significantly affect cytokine and chemokine levels. These data suggest that particulate and soluble β-glucans differentially affect the intestinal immune responses. However, no significant differences in other clinical colitis scores between soluble and particulate β-glucans were found in this study. In summary, β-glucans aggravate the course of dextran sulfate sodium (DSS)-induced intestinal inflammation at the level of the mucosa.

  4. 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.

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

    PubMed

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

    2015-09-01

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

  6. Cyclodextrin/dextran based hydrogels prepared by cross-linking with sodium trimetaphosphate.

    PubMed

    Wintgens, Véronique; Lorthioir, Cédric; Dubot, Pierre; Sébille, Bernard; Amiel, Catherine

    2015-11-01

    Novel βCD-based hydrogels have been synthesized using sodium trimetaphosphate (STMP) as non-toxic reagent. Straightforward mixing of βCD with dextran and STMP in basic aqueous media led to hydrogels incorporating dextran chains, phosphate groups and βCD units. The hydrogels have been characterized by swelling measurements, XPS and (31)P NMR. The swelling ratio was correlated to the content in phosphated groups, which give a polyelectrolyte character to these hydrogels. The significant rise of the swelling ratio with the βCD content increase has been attributed to a decrease of the number of phosphate-based crosslinks, the βCD units playing the role of dangling ends in the tridimensional network. Their loading capacity and their release properties have been investigated for methylene blue and benzophenone in order to demonstrate their potentiality for drug delivery. Through different interaction mechanisms, electrostatic and inclusion complex interactions, these compounds are loaded with different efficiencies. The release involves deswelling, diffusion mechanisms and partition equilibrium. PMID:26256327

  7. Cyclodextrin/dextran based hydrogels prepared by cross-linking with sodium trimetaphosphate.

    PubMed

    Wintgens, Véronique; Lorthioir, Cédric; Dubot, Pierre; Sébille, Bernard; Amiel, Catherine

    2015-11-01

    Novel βCD-based hydrogels have been synthesized using sodium trimetaphosphate (STMP) as non-toxic reagent. Straightforward mixing of βCD with dextran and STMP in basic aqueous media led to hydrogels incorporating dextran chains, phosphate groups and βCD units. The hydrogels have been characterized by swelling measurements, XPS and (31)P NMR. The swelling ratio was correlated to the content in phosphated groups, which give a polyelectrolyte character to these hydrogels. The significant rise of the swelling ratio with the βCD content increase has been attributed to a decrease of the number of phosphate-based crosslinks, the βCD units playing the role of dangling ends in the tridimensional network. Their loading capacity and their release properties have been investigated for methylene blue and benzophenone in order to demonstrate their potentiality for drug delivery. Through different interaction mechanisms, electrostatic and inclusion complex interactions, these compounds are loaded with different efficiencies. The release involves deswelling, diffusion mechanisms and partition equilibrium.

  8. Preventive effects of cranberry products on experimental colitis induced by dextran sulphate sodium in mice.

    PubMed

    Xiao, Xiao; Kim, Jonggun; Sun, Quancai; Kim, Daeyoung; Park, Cheon-Seok; Lu, Tzong-Shi; Park, Yeonhwa

    2015-01-15

    With the prevalence of inflammatory bowel disease (IBD) and its associated risk for development of colorectal cancer, it is of great importance to prevent and treat IBD. However, due to the complexity of etiology and potentially serious adverse effects, treatment options for IBD are relatively limited. Thus, the purpose of this study was to identify a safe food-based approach for the prevention and treatment of IBD. In this study, we tested the effects of cranberry products on preventing dextran sulphate sodium-induced murine colitis. Our results suggest that both cranberry extract and dried cranberries-fed groups had a significantly reduced disease activity index, where dried cranberries were more effective in preventing colitis than cranberry extract. Shortening of colon length, colonic myeloperoxidase activity and production of pro-inflammatory cytokines were attenuated in animals fed dried cranberries compared to the controls. The current report suggests that cranberries can be applied to prevent and reduce the symptoms of IBD.

  9. Coagulation changes in baboons during acute experimental hemoglobinemia and dextran infusion.

    PubMed Central

    Spector, J. I.; Lang, J. E.; Crosby, W. H.

    1975-01-01

    Evidence of disseminated intravascular coagulation (DIC) was dought in normal baboons infused with autologous hemolyzed whole blood, preceded or followed by infusion of dextran (molecular weight, 70,000). Mean peak plasma hemoglobin following a rapid single injection was 370 mg/100 ml in 2 animals and 1,236 mg/100 ml in 1 animal, while levels during continuous 5 hour infusion in 2 animals averaged 326 and 474 mg/100 ml, respectively. Dextran infusion immediately preceded hemoglobin injection in 2 baboons and followed hemoglobin injection by 1 1/2 and 2 1/2 hours, respectively, in 2 baboons. Coagulation studies showed a moderate although significant fall in platelet count with prolongation of the partial thromboplastin time following hemoglobin infusion, and shortening of the thrombin time after dextran. Fibrin degradation products developed in four of five experiments after hemolysate injection. The induction of acute experimental hemoglobinemia results, therefore, in the development of coagulation changes consistent with milk DIC. Preliminary infusion of dextran (molecular weight, 70,000) may facilitate this response by either initiating the development or impeding the clearance of fibrin degradation products. PMID:804256

  10. Dietary Geraniol by Oral or Enema Administration Strongly Reduces Dysbiosis and Systemic Inflammation in Dextran Sulfate Sodium-Treated Mice.

    PubMed

    De Fazio, Luigia; Spisni, Enzo; Cavazza, Elena; Strillacci, Antonio; Candela, Marco; Centanni, Manuela; Ricci, Chiara; Rizzello, Fernando; Campieri, Massimo; Valerii, Maria C

    2016-01-01

    (Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory, antitumoral, and antimicrobial properties. It is widely used as a preservative in the food industry and as an antimicrobial agent in animal farming. The present study investigated the role of Ge-OH as an anti-inflammatory and anti-dysbiotic agent in the dextran sulfate sodium (DSS)-induced colitis mouse model. Ge-OH was orally administered to C57BL/6 mice at daily doses of 30 and 120 mg kg((-1)) body weight, starting 6 days before DSS treatment and ending the day after DSS removal. Furthermore, Ge-OH 120 mg kg((-1)) dose body weight was administered via enema during the acute phase of colitis to facilitate its on-site action. The results show that orally or enema-administered Ge-OH is a powerful antimicrobial agent able to prevent colitis-associated dysbiosis and decrease the inflammatory systemic profile of colitic mice. As a whole, Ge-OH strongly improved the clinical signs of colitis and significantly reduced cyclooxygenase-2 (COX-2) expression in colonocytes and in the gut wall. Ge-OH could be a powerful drug for the treatment of intestinal inflammation and dysbiosis.

  11. Interleukin-6, but not the interleukin-6 receptor plays a role in recovery from dextran sodium sulfate-induced colitis.

    PubMed

    Sommer, Jan; Engelowski, Erika; Baran, Paul; Garbers, Christoph; Floss, Doreen M; Scheller, Jürgen

    2014-09-01

    Interleukin (IL)-6-deficient, but not IL-6 receptor (IL-6R)‑deficient mice present with a delayed skin wound healing phenotype. Since IL-6 solely signals via the IL-6R and glycoprotein 130 (gp130), Il-6r-deficient mice are expected to exhibit a similar phenotype as Il-6-deficient mice. However, p28 (IL-30) and ciliary neurotrophic factor (CNTF) have been identified as additional low‑affinity ligands of the IL-6R/gp130/LIFR complex. IL-6 plays an inflammatory and regenerative role in inflammatory bowel disease (IBD). In the present study, we compared Il-6r-deficient mice with mice treated with neutralizing IL-6 monoclonal antibody (mAb) in a model of dextran sodium sulfate (DSS)-induced colitis. Our results, in agreement with those of previous reports, demonstrated that IL-6 mAbs slightly attenuated DSS-induced colitis during the regeneration phase. Il-6r-deficient mice and mice with tissue-specific deletion of the Il-6r in the myeloid cell lineage (LysMCre) with acute and chronic DSS-induced colitis were, however, indistinguishable from wild-type mice. Our data suggest that IL-6 and IL-6R have an additional role in colitis, apart from the IL-6/IL-6R classic and trans-signaling.

  12. Dietary Geraniol by Oral or Enema Administration Strongly Reduces Dysbiosis and Systemic Inflammation in Dextran Sulfate Sodium-Treated Mice

    PubMed Central

    De Fazio, Luigia; Spisni, Enzo; Cavazza, Elena; Strillacci, Antonio; Candela, Marco; Centanni, Manuela; Ricci, Chiara; Rizzello, Fernando; Campieri, Massimo; Valerii, Maria C.

    2016-01-01

    (Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory, antitumoral, and antimicrobial properties. It is widely used as a preservative in the food industry and as an antimicrobial agent in animal farming. The present study investigated the role of Ge-OH as an anti-inflammatory and anti-dysbiotic agent in the dextran sulfate sodium (DSS)-induced colitis mouse model. Ge-OH was orally administered to C57BL/6 mice at daily doses of 30 and 120 mg kg(−1) body weight, starting 6 days before DSS treatment and ending the day after DSS removal. Furthermore, Ge-OH 120 mg kg(−1) dose body weight was administered via enema during the acute phase of colitis to facilitate its on-site action. The results show that orally or enema-administered Ge-OH is a powerful antimicrobial agent able to prevent colitis-associated dysbiosis and decrease the inflammatory systemic profile of colitic mice. As a whole, Ge-OH strongly improved the clinical signs of colitis and significantly reduced cyclooxygenase-2 (COX-2) expression in colonocytes and in the gut wall. Ge-OH could be a powerful drug for the treatment of intestinal inflammation and dysbiosis. PMID:26973525

  13. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  14. Transplantation of human umbilical mesenchymal stem cells attenuates dextran sulfate sodium-induced colitis in mice.

    PubMed

    Lin, Yan; Lin, Lianjie; Wang, Qiushi; Jin, Yu; Zhang, Ying; Cao, Yong; Zheng, Changqing

    2015-01-01

    Ulcerative colitis is a major form of inflammatory bowel disease and increases the risk of the development of colorectal carcinoma. The anti-inflammatory and immunomodulatory properties of mesenchymal stem cells (MSC) make them promising tools for treating immune-mediated and inflammatory diseases. However, the lack of robust technique for harvesting and expanding of MSC has hampered the use of bone marrow and umbilical cord blood derived MSC in clinical applications. In the present study, we investigated the intestinal protective effects of Wharton's jelly-derived umbilical MSC (UMSC) on dextran sulfate sodium-induced colitis in mice. The severity of colitis in mice was assessed using bodyweight loss, stool consistency, rectal bleeding, colon shortening and haematological parameters. Colonic myeloperoxidase and pro-inflammatory cytokines levels were also measured. Furthermore, the expression of cyclooxygenase 2 and inducible nitric oxide synthase in the colon were detected. In addition, intestinal permeability and tight junction proteins expressions in the colon were examined as well. The results showed that Wharton's jelly-derived UMSC significantly diminished the severity of colitis, reduced histolopathological score, and decreased myeloperoxidase activity and cytokines levels. Furthermore, the UMSC markedly decreased the expression of cyclooxygenase 2and inducible nitric oxide synthase in the colon. In addition, transplantation of UMSC reduced intestinal permeability and upregulated the expression of tight junction proteins. These results show that the anti-inflammation and regulation of tight junction proteins by Wharton's jelly-derived UMSC ameliorates colitis.

  15. 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.

  16. Effects of Guchang Capsule on Dextran Sulphate Sodium-Induced Experimental Ulcerative Colitis in Mice

    PubMed Central

    Liu, Baoshan; Liu, Tong; Wang, Xiaohong; Zheng, Xin; Wang, Hong; Ma, Lin

    2016-01-01

    Guchang capsule (GC) is a Chinese materia medica standardized product extracted from 15 Chinese traditional medical herbs and it has been clinically used in the treatment of intestinal disease. In this study, in order to extend the research of GC in intestinal disease, we were aiming to evaluate potential effects of GC on dextran sulphate sodium- (DSS-) induced murine experimental colitis and to elucidate the underlying mechanisms. GC treatment attenuated DSS-induced body weight loss and reduced the mortality. Moreover, GC treatment prevented DSS-induced colonic pathological damage; meanwhile it inhibited proinflammatory cytokines production in colon tissues. In vitro, GC significantly reduced LPS-induced proinflammatory cytokines production via inhibiting the activation of NF-κB in macrophage cells, and the expressions of several long noncoding RNAs (lncRNAs) which were reported in regulating NF-κB signaling pathway were obviously affected by adding GC into culture medium. In conclusion, our data suggested that administration of GC exhibits therapeutic effects on DSS-induced colitis partially through regulating the expression of NF-κB related lncRNAs in infiltrating immune cells. PMID:27313642

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

    SciTech Connect

    Kanbe, Takamasa |; Murai, Rie; Mukoyama, Tomoyuki; Murawaki, Yoshiyuki |; Hashiguchi, Ko-ichi; Yoshida, Yoko; Tsuchiya, Hiroyuki; Kurimasa, Akihiro; Harada, Ken-ichi; Yashima, Kazuo; Nishimuki, Eiji; Shabana, Noriko; Kishimoto, Yukihiro; Kojyo, Haruhiko; Miura, Kunihiko; Kawasaki, Hironaka; Murawaki, Yoshikazu; Shiota, Goshi . E-mail: gshiota@grape.med.tottori-u.ac.jp

    2006-07-14

    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 than in control mice (P < 0.01, each). Phosphorylated AKT was dramatically increased after HGF gene administration, however, phosphorylated ERK1/2 was not altered. Microarray analysis revealed that HGF induced expression of proliferation- and apoptosis-associated genes. These data suggest that naked HGF gene delivery causes therapeutic effects through regulation of many downstream genes.

  18. Effect of Nanometric Lactobacillus plantarum in Kimchi on Dextran Sulfate Sodium-Induced Colitis in Mice.

    PubMed

    Lee, Hyun Ah; Bong, Yeon-Ju; Kim, Hyunung; Jeong, Ji-Kang; Kim, Hee-Young; Lee, Kwang-Won; Park, Kun-Young

    2015-10-01

    Nanometric Lactobacillus plantarum (nLp) is a processed form of Lab. plantarum derived from kimchi and is 0.5-1.0 μm in size. This study was undertaken to determine the effect of nLp and kimchi plus nLp (K-nLp) on a dextran sulfate sodium (DSS)-induced mouse model of colitis. Animals fed nLp or K-nLp had longer colons, but lower colon weights per unit length than DSS controls. In addition, nLp- or K-nLp-fed animals showed lower levels of proinflammatory cytokines and inflammatory genes in serum and in colon tissues, lower populations of total bacteria, but higher populations of lactic acid bacteria in feces, and lower activities of fecal β-glucosidase and β-glucuronidase. Furthermore, these suppressive activities of nLp on colitis were equivalent to or higher than those of naive Lab. plantarum. Consequently, nLp was found to exhibit anticolitic effects, and the addition of nLp to kimchi was found to enhance the protective activity of kimchi against DSS-induced colitis. These results suggest that nLp might be an effective substitute for live probiotics and be useful as a functional ingredient with the anticolitic activity by the probiotic and food processing industries.

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

    PubMed

    Pandurangan, Ashok Kumar; Ismail, Salmiah; Saadatdoust, Zeinab; Esa, Norhaizan Mohd

    2015-01-01

    The objective of this study is to evaluate the effect of allicin (10 mg/kg body weight, orally) in an experimental murine model of UC by administering 2.5% dextran sodium sulfate (DSS) in drinking water to BALB/c mice. DSS-induced mice presented reduced body weight, which was improved by allicin administration. We noted increases in CD68 expression, myeloperoxidase (MPO) activities, and Malonaldehyde (MDA) and mRNA levels of proinflammatory cytokines, such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, and IL-17, and decrease in the activities of enzymic antioxidants such as superoxide dismutase (SOD), Catalase (CAT), Glutathione reductase (GR), and Glutathione peroxidase (GPx) in DSS-induced mice. However, allicin treatment significantly decreased CD68, MPO, MDA, and proinflammatory cytokines and increased the enzymic antioxidants significantly (P < 0.05). In addition, allicin was capable of reducing the activation and nuclear accumulation of signal transducer and activator of transcription 3 (STAT3), thereby preventing degradation of the inhibitory protein IκB and inducing inhibition of the nuclear translocation of nuclear factor (NF)-κB-p65 in the colonic mucosa. These findings suggest that allicin exerts clinically useful anti-inflammatory effects mediated through the suppression of the NF-κB and IL-6/p-STAT3(Y705) pathways. PMID:26075036

  20. Gallic acid suppresses inflammation in dextran sodium sulfate-induced colitis in mice: Possible mechanisms.

    PubMed

    Pandurangan, Ashok Kumar; Mohebali, Nooshin; Esa, Norhaizan Mohd; Looi, Chung Yeng; Ismail, Salmiah; Saadatdoust, Zeinab

    2015-10-01

    Inflammatory bowel diseases (IBD) encompass at least two forms of intestinal inflammation: Crohn's disease and ulcerative colitis (UC). Both conditions are chronic and inflammatory disorders in the gastrointestinal tract, with an increasing prevalence being associated with the industrialization of nations and in developing countries. Patients with these disorders are 10 to 20 times more likely to develop cancer of the colon. The aim of this study was to characterize the effects of a naturally occurring polyphenol, gallic acid (GA), in an experimental murine model of UC. A significant blunting of weight loss and clinical symptoms was observed in dextran sodium sulfate (DSS)-exposed, GA-treated mice compared with control mice. This effect was associated with a remarkable amelioration of the disruption of the colonic architecture, a significant reduction in colonic myeloperoxidase (MPO) activity, and a decrease in the expression of inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and pro-inflammatory cytokines. In addition, GA reduced the activation and nuclear accumulation of p-STAT3(Y705), preventing the degradation of the inhibitory protein IκB and inhibiting of the nuclear translocation of p65-NF-κB in colonic mucosa. These findings suggest that GA exerts potentially clinically useful anti-inflammatory effects mediated through the suppression of p65-NF-κB and IL-6/p-STAT3(Y705) activation.

  1. Protective Effect of Calculus Bovis Sativus on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice.

    PubMed

    Li, Xiping; Xu, Yanjiao; Zhang, Chengliang; Deng, Li; Chang, Mujun; Yu, Zaoqin; Liu, Dong

    2015-01-01

    Calculus Bovis Sativus (CBS) is a commonly used traditional Chinese medicine, which has been reported to exhibit antispasmodic, fever-reducing, anti-inflammatory, and gallbladder-repairing effects. The present study aims to investigate the protective effect of CBS on dextran sulphate sodium- (DSS-) induced ulcerative colitis (UC) in mice. C57BL/6 male mice were exposed to 5% DSS in drinking water. CBS was given orally at 50 and 150 mg/kg once per day for 7 days. Body weight, disease activity index (DAI), colon length, colonic myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and nitric oxide (NO) levels were measured. Administration of CBS significantly reserved these changes, decreased the MPO activity and MDA and NO level, and increased the SOD activity in the colon tissue. Histological observation suggested that CBS alleviated edema, mucosal damage, and inflammatory cells infiltration induced by DSS in the colon. Moreover, CBS significantly downregulated the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin- (IL-) 1β and IL-6 in the colon tissue. Our data suggested that CBS exerted protective effect on DSS-induced UC partially through the antioxidant and anti-inflammatory activities. PMID:26579201

  2. Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice.

    PubMed

    Håkansson, Å; Tormo-Badia, N; Baridi, A; Xu, J; Molin, G; Hagslätt, M-L; Karlsson, C; Jeppsson, B; Cilio, C M; Ahrné, S

    2015-02-01

    Ulcerative colitis (UC) is characterized by chronic inflammation of the colonic mucosa. Administration of dextran sulfate sodium (DSS) to animals is a frequently used model to mimic human colitis. Deregulation of the immune response to the enteric microflora or pathogens as well as increased intestinal permeability have been proposed as disease-driving mechanisms. To enlarge the understanding of the pathogenesis, we have studied the effect of DSS on the immune system and gut microbiota in mice. Intestinal inflammation was verified through histological evaluation and myeloperoxidase activity. Immunological changes were assessed by flow cytometry in spleen, Peyer's patches and mesenteric lymph nodes and through multiplex cytokine profiling. In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. DSS-induced colitis show clinical and histological similarities to UC. The composition of the colonic microflora was profoundly changed and correlated with several alterations of the immune system. The results demonstrate a relationship between multiple immunological changes and alterations of the gut microbiota after DSS administration. These data highlight and improve the definition of the immunological basis of the disease and suggest a role for dysregulation of the gut microbiota in the pathogenesis of colitis.

  3. Fumigaclavine C ameliorates dextran sulfate sodium-induced murine experimental colitis via NLRP3 inflammasome inhibition.

    PubMed

    Guo, Wenjie; Hu, Shasha; Elgehama, Ahmed; Shao, Fenli; Ren, Ren; Liu, Wen; Zhang, Wenjing; Wang, Xinlei; Tan, Renxiang; Xu, Qiang; Sun, Yang; Jiao, Ruihua

    2015-10-01

    In the present study, the effect of Fumigaclavine C, a fungal metabolite, on murine experimental colitis induced by dextran sulfate sodium (DSS) and its possible mechanism were examined in vivo and vitro. Oral administration of Fumigaclavine C dose-dependently attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic scores of musco was also significantly reduced by Fumigaclavine C treatment. Protein and mRNA levels of DSS-induced pro-inflammatory cytokines in colon, including TNF-α, IL-1β and IL-17A, were markedly suppressed by Fumigaclavine C. At the same time, decreased activation of caspase-1 in peritoneal macrophages was detected in Fumigaclavine C -treated mice which suggested that the NLRP3 inflammasome activation was suppressed. Furthermore, in the LPS plus ATP cell model, we found that Fumigaclavine C dose-dependent inhibited IL-1β release and caspase-1 activation. Taken together, our results demonstrate the ability of Fumigaclavine C to inhibit NLRP3 inflammasome activation and give some evidence for its potential use in the treatment of inflammatory bowel diseases. PMID:26320672

  4. Myristica fragrans seed extract protects against dextran sulfate sodium-induced colitis in mice.

    PubMed

    Kim, Hyojung; Bu, Youngmin; Lee, Beom-Joon; Bae, Jinhyun; Park, Sujin; Kim, Jinsung; Lee, Kyungjin; Cha, Jae-Myung; Ryu, Bongha; Ko, Seok-Jae; Han, Gajin; Min, Byungil; Park, Jae-Woo

    2013-10-01

    Nutmeg (seed of Myristica fragrans [MF]) is one of the most commonly used spices in the world and also a well-known herb for the treatment of various intestinal diseases, including colitis in traditional Korean medicine. The purpose of the current study was to investigate whether water extract of MF (MFE) can protect against dextran sulfate sodium (DSS) induced colitis in a mouse model. Colitis was induced by 5% DSS in balb/c mice. MFE (100, 300 or 1000 mg/kg) was orally administered to the mice twice a day for 7 days. Body weight, colon length, clinical score, and histological score were assessed to determine the effects on colitis. Proinflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) were measured to investigate the mechanisms of action. MFE dose dependently inhibited the colon shortening and histological damage to the colon. However, it did not prevent weight loss. MFE also inhibited proinflammatory cytokines. The current results suggest that MFE ameliorates DSS-induced colitis in mice by inhibiting inflammatory cytokines. Further investigation, including the exact mechanisms is needed. PMID:24063406

  5. Protective Effect of Calculus Bovis Sativus on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice

    PubMed Central

    Li, Xiping; Xu, Yanjiao; Zhang, Chengliang; Deng, Li; Chang, Mujun; Yu, Zaoqin; Liu, Dong

    2015-01-01

    Calculus Bovis Sativus (CBS) is a commonly used traditional Chinese medicine, which has been reported to exhibit antispasmodic, fever-reducing, anti-inflammatory, and gallbladder-repairing effects. The present study aims to investigate the protective effect of CBS on dextran sulphate sodium- (DSS-) induced ulcerative colitis (UC) in mice. C57BL/6 male mice were exposed to 5% DSS in drinking water. CBS was given orally at 50 and 150 mg/kg once per day for 7 days. Body weight, disease activity index (DAI), colon length, colonic myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and nitric oxide (NO) levels were measured. Administration of CBS significantly reserved these changes, decreased the MPO activity and MDA and NO level, and increased the SOD activity in the colon tissue. Histological observation suggested that CBS alleviated edema, mucosal damage, and inflammatory cells infiltration induced by DSS in the colon. Moreover, CBS significantly downregulated the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin- (IL-) 1β and IL-6 in the colon tissue. Our data suggested that CBS exerted protective effect on DSS-induced UC partially through the antioxidant and anti-inflammatory activities. PMID:26579201

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

    PubMed

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

    2015-06-01

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

  7. Kimchi protects against azoxymethane/dextran sulfate sodium-induced colorectal carcinogenesis in mice.

    PubMed

    Kim, Hee-Young; Song, Jia-Le; Chang, Hee-Kyung; Kang, Soon-Ah; Park, Kun-Young

    2014-08-01

    The chemopreventive effects of different types and quantities of kimchi prepared with different subingredients, including commercial kimchi (CK), standardized kimchi (SK), cancer-preventive kimchi (CPK), and anticancer kimchi (ACK), on colorectal carcinogenesis in mice were evaluated. The development of colon cancer was induced in male BALB/c mice with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and subsequent treatment with 2% dextran sulfate sodium (DSS) in drinking water for 7 days for two cycles. After exposure to AOM and DSS, treatment with the methanolic extracts from different kimchis, particularly 1.89 g/kg of ACK, significantly increased colon length, decreased the ratio of colon weight/length, and resulted in the lowest number of tumors compared with the other kimchi-treated groups. Histological observation revealed that ACK was able to suppress AOM- and DSS-induced colonic mucosal damage and neoplasia. ACK also significantly decreased the mRNA levels of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) as well as the mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2). In addition, the mRNA and protein expression of p53 and p21 was elevated in colon tissues from the ACK-treated mice compared with the other kimchi-treated groups. Our results suggest that kimchi exerted a suppressive effect on AOM- and DSS-induced colorectal carcinogenesis in the BALB/c mice. The anticancer effects of ACK were particularly potent. Thus, it is possible that the health-promoting subingredients added to ACK might be used to prevent colon carcinogenesis in humans. PMID:25029638

  8. Propionate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation and Oxidative Stress.

    PubMed

    Tong, Ling-Chang; Wang, Yue; Wang, Zhi-Bin; Liu, Wei-Ye; Sun, Sheng; Li, Ling; Su, Ding-Feng; Zhang, Li-Chao

    2016-01-01

    Propionate is a short chain fatty acid that is abundant as butyrate in the gut and blood. However, propionate has not been studied as extensively as butyrate in the treatment of colitis. The present study was to investigate the effects of sodium propionate on intestinal barrier function, inflammation and oxidative stress in dextran sulfate sodium (DSS)-induced colitis mice. Animals in DSS group received drinking water from 1 to 6 days and DSS [3% (w/v) dissolved in double distilled water] instead of drinking water from 7 to 14 days. Animals in DSS+propionate (DSS+Prop) group were given 1% sodium propionate for 14 consecutive days and supplemented with 3% DSS solution on day 7-14. Intestinal barrier function, proinflammatory factors, oxidative stress, and signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon were determined. It was found that sodium propionate ameliorated body weight loss, colon-length shortening and colonic damage in colitis mice. Sodium propionate significantly inhibited the increase of FITC-dextran in serum and the decrease of zonula occludens-1 (ZO-1), occludin, and E-cadherin expression in the colonic tissue. It also inhibited the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA and phosphorylation of STAT3 in colitis mice markedly, reduced the myeloperoxidase (MPO) level, and increased the superoxide dismutase and catalase level in colon and serum compared with DSS group. Sodium propionate inhibited macrophages with CD68 marker infiltration into the colonic mucosa of colitis mice. These results suggest that oral administration of sodium propionate could ameliorate DSS-induced colitis mainly by improving intestinal barrier function and reducing inflammation and oxidative stress via the STAT3 signaling pathway. PMID:27574508

  9. Propionate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation and Oxidative Stress

    PubMed Central

    Tong, Ling-chang; Wang, Yue; Wang, Zhi-bin; Liu, Wei-ye; Sun, Sheng; Li, Ling; Su, Ding-feng; Zhang, Li-chao

    2016-01-01

    Propionate is a short chain fatty acid that is abundant as butyrate in the gut and blood. However, propionate has not been studied as extensively as butyrate in the treatment of colitis. The present study was to investigate the effects of sodium propionate on intestinal barrier function, inflammation and oxidative stress in dextran sulfate sodium (DSS)-induced colitis mice. Animals in DSS group received drinking water from 1 to 6 days and DSS [3% (w/v) dissolved in double distilled water] instead of drinking water from 7 to 14 days. Animals in DSS+propionate (DSS+Prop) group were given 1% sodium propionate for 14 consecutive days and supplemented with 3% DSS solution on day 7–14. Intestinal barrier function, proinflammatory factors, oxidative stress, and signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon were determined. It was found that sodium propionate ameliorated body weight loss, colon-length shortening and colonic damage in colitis mice. Sodium propionate significantly inhibited the increase of FITC-dextran in serum and the decrease of zonula occludens-1 (ZO-1), occludin, and E-cadherin expression in the colonic tissue. It also inhibited the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA and phosphorylation of STAT3 in colitis mice markedly, reduced the myeloperoxidase (MPO) level, and increased the superoxide dismutase and catalase level in colon and serum compared with DSS group. Sodium propionate inhibited macrophages with CD68 marker infiltration into the colonic mucosa of colitis mice. These results suggest that oral administration of sodium propionate could ameliorate DSS-induced colitis mainly by improving intestinal barrier function and reducing inflammation and oxidative stress via the STAT3 signaling pathway. PMID:27574508

  10. Histopathological and morphometric changes induced by a dextran sodium sulfate (DSS) model in broilers.

    PubMed

    Menconi, A; Hernandez-Velasco, X; Vicuña, E A; Kuttappan, V A; Faulkner, O B; Tellez, G; Hargis, B M; Bielke, L R

    2015-05-01

    Oral administration of dextran sodium sulfate (DSS) is commonly used as an inducer of enteric inflammation in rodents. However, there is a dearth of knowledge regarding appropriate dosage, timing, or ageresponses in broilers for this potential inducer of inflammation without necrosis. Two experiments were conducted in day-of-hatch chicks to analyze clinical parameters and enteric histological changes induced by DSS when administered via drinking water ( DW: ). In both experiments, birds were distributed into nontreated control or varying concentrations of DSS in DW. For both experiments, only 0.75% DSS in DW was histologically evaluated. In Experiment 1, chicks received DSS from day 3 to 11, and at 3, 6, and 8 d of treatment, chicks were weighed, and sections of the duodenum, ileum, and ceca were formalin fixed. The addition of 0.75% DSS caused depression, anemia, and watery bloody diarrhea, plus significantly (P < 0.05) decreased BW gain at all times. Shortened ileal villi at 6 d and duodenal villi at 8 d of treatment, reduced duodenal and ileal epithelial cell height at 3, 6, and 8 d, and increased duodenal goblet cell density at 6 and 8 d were observed in response to DSS administration (P < 0.05). In Experiment 2, birds received DSS from days 10 to 16 and were sampled at 3 and 6 d of treatment. Similar changes were found in ceca of treated birds. There was no significant change in the duodenal villus height and goblet cell density by 6 d of treatment, suggesting that 6 d of 0.75% DSS in DW was not sufficient for the reproduction of duodenal symptoms in these older birds. However, there was a significant decrease in ilealvillus height and decreased ileal epithelial cell height at 3 and 6 d of treatment, as well as a significant decrease in BW compared to the control group. These findings indicate that DW administration of 0.75% DSS caused generalized mild and non-necrotic enteritis in broilers and that this compound may be useful for enteric inflammation modeling

  11. Oral tolerance is inducible during active dextran sulfate sodium-induced colitis

    PubMed Central

    Ino, Satoshi; Kohda, Chikara; Takeshima, Kosuke; Ishikawa, Hiroki; Norose, Tomoko; Yamochi, Toshiko; Takimoto, Masafumi; Takahashi, Hiroshi; Tanaka, Kazuo

    2016-01-01

    AIM: To investigate whether oral tolerance is inducible during the active phase of dextran sulfate sodium (DSS)-induced colitis. METHODS: Colitis was induced in 6- to 8-wk-old female BALB/c mice by the administration of 2% DSS. To induce oral tolerance, mice that received water with DSS [DSS (+)] and mice that received autoclaved water [DSS (-)] were intragastrically (i.g.) administered ovalbumin (OVA) as a tolerogen before systemic challenge with OVA. Following this, serum levels of OVA-specific IgE antibodies were measured. In mice with active colitis, CD4+CD25+Foxp3+ cell and B10 cell frequencies were evaluated using flow cytometry. Cytokine mRNA expression profiles were evaluated by reverse transcription real-time polymerase chain reaction. RESULTS: Regardless of the presence of DSS colitis, OVA-specific immunoglobulin E concentrations were significantly reduced in mice that were i.g. administered OVA compared to mice that were i.g. administered PBS [DSS (+): 4.4 (4.2-9.5) ng/mL vs 83.9 (66.1-123.2) ng/mL, P < 0.01; DSS (-): 27.7 (0.1-54.5) ng/mL vs 116.5 (80.6-213.6) ng/mL, P < 0.01]. These results demonstrated that oral tolerance was induced in both the presence and absence of colitis. In the spleen and mesenteric lymph nodes (MLN), the frequencies of CD4+CD25+Foxp3+ cells and B10 cells, both of which are associated with oral tolerance, did not significantly change. In the spleen, interferon-γ mRNA expression significantly decreased in mice with colitis [DSS (+): 0.42 (0.31-0.53) vs DSS (-): 1.00 (0.84-1.39), P < 0.01]. The expression levels of other cytokines did not significantly change. CONCLUSION: Oral tolerance is inducible during active DSS colitis. The stability of regulatory cell populations in the spleen and MLN in colitis might correlate with these results. PMID:27158540

  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. Faecalibacterium prausnitzii supernatant ameliorates dextran sulfate sodium induced colitis by regulating Th17 cell differentiation

    PubMed Central

    Huang, Xiao-Li; Zhang, Xin; Fei, Xian-Yan; Chen, Zhao-Gui; Hao, Yan-Ping; Zhang, Shu; Zhang, Ming-Ming; Yu, Yan-Qiu; Yu, Cheng-Gong

    2016-01-01

    AIM: To explore the preventive and therapeutic effects of Faecalibacterium prausnitzii (F. prausnitzii) supernatant on dextran sulfate sodium (DSS) induced colitis in mice. METHODS: Forty C57BL/6J male mice were randomly divided into four groups: control group, model group, treatment group, and prevention group. Mice were weighed daily. On day 10, the colon length was measured, the colorectal histopathologic damage score (HDS) was assessed, and plasma interleukin (IL)-17A, IL-6, and IL-4 levels were detected by enzyme-linked immunosorbent assay. The expression of transcription factor retinoic acid-related orphan receptor-γt (RORγt) and IL-17A in colon inflammatory mucosa tissue were determined by immunohistochemical assay, and the expression levels of RORγt mRNA, IL-17A mRNA, and IL-6 mRNA were detected by real-time quantitative polymerase chain reaction (PCR). The proportion of Th17 in mononuclear cells in spleen was assayed by fluorescence activated cell sorter. RESULTS: When compared with the model group, the colon length (P < 0.05) and body weight (P < 0.01) in the treatment and prevention groups were significantly increased, and the colon HDS was decreased (P < 0.05 and P < 0.01). There was no statistical difference between the treatment group and prevention group. After treatment with F. prausnitzii supernatant, the plasma levels of IL-17A and IL-6 (P < 0.05), the protein and mRNA expression of IL-17A and RORγt, and the Th17 cell ratio of spleen cells (P < 0.01) were significantly decreased compared to the model group. Plasma IL-4 level in the prevention group was significantly higher than that in the model group (P < 0.05), but there was no significant difference between these two groups in the expression of IL-6 in both the plasma and colon mucosa tissues. CONCLUSION: F. prausnitzii supernatant exerts protective and therapeutic effects on DSS-induced colitis in mice, probably via inhibition of Th17 differentiation and IL-17A secretion in the plasma and

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

    PubMed Central

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

    2015-01-01

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

  15. Ethanol extract of Cordyceps militaris grown on germinated soybeans attenuates dextran-sodium-sulfate- (DSS-) induced colitis by suppressing the expression of matrix metalloproteinases and inflammatory mediators.

    PubMed

    Park, Dong Ki; Park, Hye-Jin

    2013-01-01

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

  16. Bifidobacterium longum Alleviates Dextran Sulfate Sodium-Induced Colitis by Suppressing IL-17A Response: Involvement of Intestinal Epithelial Costimulatory Molecules

    PubMed Central

    Miyauchi, Eiji; Ogita, Tasuku; Miyamoto, Junki; Kawamoto, Seiji; Morita, Hidetoshi; Ohno, Hiroshi; Suzuki, Takuya; Tanabe, Soichi

    2013-01-01

    Although some bacterial strains show potential to prevent colitis, their mechanisms are not fully understood. Here, we investigated the anti-colitic mechanisms of Bifidobacterium longum subsp. infantis JCM 1222T, focusing on the relationship between interleukin (IL)-17A secreting CD4+ T cells and intestinal epithelial costimulatory molecules in mice. Oral administration of JCM 1222T to mice alleviated dextran sulfate sodium (DSS)-induced acute colitis. The expression of type 1 helper T (Th1)- and IL-17 producing helper T (Th17)-specific cytokines and transcriptional factors was suppressed by JCM 1222T treatment. Intestinal epithelial cells (IECs) from colitic mice induced IL-17A production from CD4+ T cells in a cell-cell contact-dependent manner, and this was suppressed by oral treatment with JCM 1222T. Using blocking antibodies for costimulatory molecules, we revealed that epithelial costimulatory molecules including CD80 and CD40, which were highly expressed in IECs from colitic mice, were involved in IEC-induced IL-17A response. Treatment of mice and intestinal epithelial cell line Colon-26 cells with JCM 1222T decreased the expression of CD80 and CD40. Collectively, these data indicate that JCM 1222T negatively regulate epithelial costimulatory molecules, and this effect might be attributed, at least in part, to suppression of IL-17A in DSS-induced colitis. PMID:24255712

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2016-08-01

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

  19. 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. PMID:19459686

  20. Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice.

    PubMed

    Di Benedetto, M; Kourbali, Y; Starzec, A; Vassy, R; Jozefonvicz, J; Perret, G; Crepin, M; Kraemer, M

    2001-09-14

    Sodium phenylacetate (NaPa) and carboxymethyl benzylamide dextran derivative (CMDB(LS4)) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDB(LS4)may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDB(LS4)potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDB(LS4)and NaPa concentrations. In nude mice, CMDB(LS4)(150 mg kg(-1)) or NaPa (40 mg kg(-1)) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDB(LS4)and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDB(LS4)action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDB(LS4)added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDB(LS4)involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of dextran derivatives with NaPa to inhibit the breast tumour growth.

  1. Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice

    PubMed Central

    Benedetto, M Di; Kourbali, Y; Starzec, A; Vassy, R; Jozefonvicz, J; Perret, G; Crepin, M; Kraemer, M

    2001-01-01

    Sodium phenylacetate (NaPa) and carboxymethyl benzylamide dextran derivative (CMDBLS4) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDBLS4 may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDBLS4 potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDBLS4 and NaPa concentrations. In nude mice, CMDBLS4 (150 mg kg−1) or NaPa (40 mg kg−1) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDBLS4 and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDBLS4 action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDBLS4 added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDBLS4 involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of dextran derivatives with NaPa to inhibit the breast tumour growth. © 2001 Cancer Research Campaignhttp://www.bjcancer.com PMID:11556846

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

    PubMed Central

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

    2016-01-01

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

  3. Inhibition of vasoactive intestinal polypeptide (VIP) induces resistance to dextran sodium sulfate (DSS)-induced colitis in mice.

    PubMed

    Vu, John P; Million, Mulugeta; Larauche, Muriel; Luong, Leon; Norris, Joshua; Waschek, James A; Pothoulakis, Charalabos; Pisegna, Joseph R; Germano, Patrizia M

    2014-01-01

    VIP is highly expressed in the colon and regulates motility, vasodilatation, and sphincter relaxation. However, its role in the development and progress of colitis is still controversial. Our aim was to determine the participation of VIP on dextran sodium sulfate (DSS)-induced colonic mucosal inflammation using VIP(-/-) and WT mice treated with VIP antagonists. Colitis was induced in 32 adult VIP(-/-) and 14 age-matched WT litter-mates by giving 2.5 % DSS in the drinking water. DSS-treated WT mice were injected daily with VIP antagonists, VIPHyb (n = 22), PG 97-269 (n = 9), or vehicle (n = 31). After euthanasia, colons were examined; colonic cytokines mRNA were quantified. VIP(-/-) mice were remarkably resistant to DSS-induced colitis compared to WT. Similarly, DSS-treated WT mice injected with VIPHyb (1 μM) or PG 97-269 (1 nM) had significantly reduced clinical signs of colitis. Furthermore, colonic expression of IL-1ϐ, TNF-α, and IL-6 was significantly lower in VIP(-/-) and VIPHyb or PG 97-269 compared to vehicle-treated WT. Genetic deletion of VIP or pharmacological inhibition of VIP receptors resulted in resistance to colitis. These data demonstrate a pro-inflammatory role for VIP in murine colitis and suggest that VIP antagonists may be an effective clinical treatment for human inflammatory bowel diseases.

  4. Protective Effect of Ceratonia siliqua L. Against a Dextran Sulfate Sodium-Induced Alterations in Liver and Kidney in Rat.

    PubMed

    Rtibi, Kaïs; Selmi, Slimen; Jabri, Mohammed-Amine; El-Benna, Jamel; Amri, Mohamed; Marzouki, Lamjed; Sebai, Hichem

    2016-09-01

    The aim of the present study is to investigate the potential protective role of Ceratonia siliqua L. against dextran sodium sulfate (DSS)-induced oxidative damage and inflammation in liver and kidney of rats. The hepatotoxicity and nephrotoxicity were induced in rats by oral administration of synthetic DSS (5%) in the drinking water for over 7 days. However, carob pods aqueous extract (CPAE; 50 and 100 mg/kg body weight) was given by oral administration for 21 days. Myeloperoxidase (MPO) activity, malondialdehyde, H2O2 content, as well as the levels of antioxidant enzymes in organs were measured to observe the possible mechanisms. As a result, the CPAE counteracted DSS-induced increase of MPO activity, lipoperoxidation, and the activity of antioxidant enzymes, such as superoxide dismutase and catalase (CAT). DSS administration increased also in the organs hydrogen peroxide (H2O2) and free iron levels, whereas the CPAE pretreatment reversed all intracellular mediator perturbations. It was concluded that the CPAE exerted a potential protective effect against DSS-induced inflammation and oxidative stress in the rat organs. Consequently, it is essential that adequate care is taken when we use carob pods for patients with hepatotoxicity and nephrotoxicity. PMID:27627702

  5. Dextran sulfate sodium upregulates MAPK signaling for the uptake and subsequent intracellular survival of Brucella abortus in murine macrophages.

    PubMed

    Reyes, Alisha Wehdnesday Bernardo; Arayan, Lauren Togonon; Simborio, Hannah Leah Tadeja; Hop, Huynh Tan; Min, WonGi; Lee, Hu Jang; Kim, Dong Hee; Chang, Hong Hee; Kim, Suk

    2016-02-01

    Brucellosis is one of the major zoonoses worldwide that inflicts important health problems in animal and human. Here, we demonstrated that dextran sulfate sodium (DSS) significantly increased adhesion of Brucella (B.) abortus in murine macrophages compared to untreated cells. Even without infection, Brucella uptake into macrophages increased and F-actin reorganization was induced compared with untreated cells. Furthermore, DSS increased the phosphorylation of MAPKs (ERK1/2 and p38α) in Brucella-infected, DSS-treated cells compared with the control cells. Lastly, DSS markedly increased the intracellular survival of Brucella abortus in macrophages by up to 48 h. These results suggest that DSS enhanced the adhesion and phagocytosis of B. abortus into murine macrophages by stimulating the MAPK signaling proteins phospho-ERK1/2 and p38α and that DSS increased the intracellular survival of B. abortus by inhibiting colocalization of Brucella-containing vacuoles (BCVs) with the late endosome marker LAMP-1. This study emphasizes the enhancement of the phagocytic and intracellular modulatory effects of DSS, which may suppress the innate immune system and contribute to prolonged Brucella survival and chronic infection.

  6. Ascorbic acid ameliorates oxidative stress and inflammation in dextran sulfate sodium-induced ulcerative colitis in mice

    PubMed Central

    Yan, Haiyan; Wang, Hongjuan; Zhang, Xiaoli; Li, Xiaoqin; Yu, Jing

    2015-01-01

    Ascorbic acid (AA) has been shown to exert beneficial effects, including mitigating oxidative stress and inhibiting inflammation. However, the preventative effect of vitamin C in chronic inflammatory diseases such as inflammatory bowel disease (IBD) remains unclear. In our study, we investigated the anti-inflammatory effects of AA and possible mechanism involved in inhibiting dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. Male C57BL/6 mice were randomly divided to three groups: control group, DSS group, and DSS plus ascorbic acid treated group. Several clinical and inflammatory parameters as well as oxidative stress were evaluated. The results demonstrated that ascorbic acid significantly reduced clinical signs, inflammatory cytokines, myeloperoxidase (MPO) and malonaldehyde (MDA) activities, whereas the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were increased in DSS-induced mice. In addition, ascorbic acid was capable of inhibiting NF-κB, COX-2 and iNOS expression in the colonic. Taken together, these findings suggest that ascorbic acid contributes to the reduction of oxidative stress and inflammatory response in DSS-induced colitis and exerts the potential to prevent and clinical treatment of inflammatory bowel disease. PMID:26884937

  7. The Algal Meroterpene 11-Hydroxy-1'-O-Methylamentadione Ameloriates Dextran Sulfate Sodium-Induced Colitis in Mice.

    PubMed

    Zbakh, Hanaa; Talero, Elena; Avila, Javier; Alcaide, Antonio; de Los Reyes, Carolina; Zubía, Eva; Motilva, Virginia

    2016-01-01

    Inflammatory bowel disease (IBD) is a complex class of immune disorders. Unfortunately, a treatment for total remission has not yet been found, while the use of natural product-based therapies has emerged as a promising intervention. The present study was aimed to investigate the anti-inflammatory effects of the algal meroterpene 11-hydroxy-1'-O-methylamentadione (AMT-E) in a murine model of dextran sodium sulphate (DSS)-induced colitis. AMT-E was orally administered daily (1, 10, and 20 mg/kg animal) to DSS treated mice (3% w/v) for 7 days. AMT-E prevented body weight loss and colon shortening and effectively attenuated the extent of the colonic damage. Similarly, AMT-E increased mucus production and reduced myeloperoxidase activity (marker for anti-inflammatory activity). Moreover, the algal meroterpene decreased the tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10 levels, and caused a significant reduction of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Our results demonstrate the protective effects of AMT-E on experimental colitis, provide an insight of the underlying mechanisms of this compound, and suggest that this class of marine natural products might be an interesting candidate for further studies on the prevention/treatment of IBD. PMID:27527191

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

    PubMed Central

    Lombardi, Valter R. M.; Etcheverría, Ignacio; Carrera, Iván; Cacabelos, Ramón; Chacón, Antonio R.

    2012-01-01

    One of the main treatments currently used in humans to fight cancer is chemotherapy. A huge number of compounds with antitumor activity are present in nature, and many of their derivatives are produced by microorganisms. However, the search for new drugs still represents a main objective for cancer therapy, due to drug toxicity and resistance to multiple chemotherapeutic drugs. In animal models, a short-time oral administration of dextran sulfate sodium (DSS) induces colitis, which exhibits several clinical and histological features similar to ulcerative colitis (UC). However, the pathogenic factors responsible for DSS-induced colitis and the subsequent colon cancer also remain unclear. We investigated the effect of FR91, a standardized lysate of microbial cells belonging to the Bacillus genus which has been previously shown to have significant immunomodulatory effects, against intestinal inflammation. Colitis was induced in mice during 5 weeks by oral administration 2% (DSS). Morphological changes in the colonic mucosa were evaluated by hematoxylin-eosin staining and immunohistochemistry methods. Adenocarcinoma and cryptal cells of the dysplastic epithelium showed cathenin-β, MLH1, APC, and p53 expression, together with increased production of IFN-γ. In our model, the optimal dose response was the 20% FR91 concentration, where no histological alterations or mild DSS-induced lesions were observed. These results indicate that FR91 may act as a chemopreventive agent against inflammation in mice DSS-induced colitis. PMID:22619498

  9. The Algal Meroterpene 11-Hydroxy-1′-O-Methylamentadione Ameloriates Dextran Sulfate Sodium-Induced Colitis in Mice

    PubMed Central

    Zbakh, Hanaa; Talero, Elena; Avila, Javier; Alcaide, Antonio; de los Reyes, Carolina; Zubía, Eva; Motilva, Virginia

    2016-01-01

    Inflammatory bowel disease (IBD) is a complex class of immune disorders. Unfortunately, a treatment for total remission has not yet been found, while the use of natural product-based therapies has emerged as a promising intervention. The present study was aimed to investigate the anti-inflammatory effects of the algal meroterpene 11-hydroxy-1′-O-methylamentadione (AMT-E) in a murine model of dextran sodium sulphate (DSS)-induced colitis. AMT-E was orally administered daily (1, 10, and 20 mg/kg animal) to DSS treated mice (3% w/v) for 7 days. AMT-E prevented body weight loss and colon shortening and effectively attenuated the extent of the colonic damage. Similarly, AMT-E increased mucus production and reduced myeloperoxidase activity (marker for anti-inflammatory activity). Moreover, the algal meroterpene decreased the tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10 levels, and caused a significant reduction of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Our results demonstrate the protective effects of AMT-E on experimental colitis, provide an insight of the underlying mechanisms of this compound, and suggest that this class of marine natural products might be an interesting candidate for further studies on the prevention/treatment of IBD. PMID:27527191

  10. Activation of intestinal human pregnane X receptor protects against azoxymethane/dextran sulfate sodium-induced colon cancer.

    PubMed

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

    2014-12-01

    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

  11. Preventive Effects of Spirogyra neglecta and a Polysaccharide Extract against Dextran Sodium Sulfate Induced Colitis in Mice.

    PubMed

    Taya, Sirinya; Kakehashi, Anna; Wongpoomchai, Rawiwan; Gi, Min; Ishii, Naomi; Wanibuchi, Hideki

    2016-01-01

    Ulcerative colitis (UC) results from colonic epithelial barrier defects and impaired mucosal immune responses. In this study, we aimed to investigate the modifying effects of a Spirogyra neglecta extract (SNE), a polysaccharide extract (PE) and a chloroform fraction (CF) on dextran sodium sulfate (DSS)-induced colitis in mice and to determine the mechanisms. To induce colitis, ICR mice received 3% DSS in their drinking water for 7 days. Seven days preceding the DSS treatment, oral administration of SNE, PE and CF at doses of 50, 25 and 0.25 mg/kg body weight (low dose), 200, 100 and 1 mg/kg body weight (high dose) and vehicle was started and continued for 14 days. Histologic findings showed that DSS-induced damage of colonic epithelial structure and inflammation was attenuated in mice pre-treated with SNE, PE and CF. Furthermore, SNE and PE significantly protected colonic epithelial cells from DSS-induced cell cycle arrest, while SNE, PE and CF significantly diminished apoptosis. Proteome analysis demonstrated that SNE and PE might ameliorate DSS-induced colitis by inducing antioxidant enzymes, restoring impaired mitochondria function, and regulating inflammatory cytokines, proliferation and apoptosis. These results suggest that SNE and PE could prevent DSS-induced colitis in ICR mice by protection against and/or aiding recovery from damage to the colonic epithelium, reducing ROS and maintaining normal mitochondrial function and apoptosis.

  12. Tanshinone IIA Protects against Dextran Sulfate Sodium- (DSS-) Induced Colitis in Mice by Modulation of Neutrophil Infiltration and Activation.

    PubMed

    Liu, Xiaowei; He, Haiyue; Huang, Tingting; Lei, Zhen; Liu, Fuquan; An, Guangyu; Wen, Tao

    2016-01-01

    Neutrophils play a critical role in the initiation and maintenance of intestinal inflammation. However, conventional neutrophil-targeted therapies can impair normal host defense. Tanshinone IIA has been recently revealed to act directly on neutrophils. Hence, we aimed at investigating whether Tanshinone IIA can protect against experimental colitis through modulation of neutrophils. We induced colitis in C57BL/6 mice by giving 3% dextran sulfate sodium (DSS) orally, and meanwhile, we treated mice daily with Tanshinone IIA intraperitoneally. The severity of colitis was evaluated by calculating disease activity index (DAI) and histological parameters. Neutrophil infiltration and activation in the colons of mice were measured. Moreover, whether Tanshinone IIA has direct effects on neutrophil migration and activation was determined in vitro. Our data showed that Tanshinone IIA significantly ameliorated the severity of DSS-induced colitis in mice, evidenced by the reduced DAI and improved colonic inflammation. In addition, Tanshinone IIA decreased neutrophil infiltration of intestinal mucosa and activation and reduced colonic inflammatory cytokines in DSS-treated mice. Furthermore, Tanshinone IIA was demonstrated to significantly suppress neutrophil migration and activation. These results provide compelling evidence that Tanshinone IIA has a therapeutic potential for alleviating inflammatory colitis in mice, which is possibly mediated by the immunomodulation of neutrophils.

  13. White and dark kidney beans reduce colonic mucosal damage and inflammation in response to dextran sodium sulfate.

    PubMed

    Monk, Jennifer M; Zhang, Claire P; Wu, Wenqing; Zarepoor, Leila; Lu, Jenifer T; Liu, Ronghua; Pauls, K Peter; Wood, Geoffrey A; Tsao, Rong; Robinson, Lindsay E; Power, Krista A

    2015-07-01

    Common beans are a rich source of nondigestible fermentable components and phenolic compounds that have anti-inflammatory effects. We assessed the gut-health-promoting potential of kidney beans in healthy mice and their ability to attenuate colonic inflammation following dextran sodium sulphate (DSS) exposure (via drinking water, 2% DSS w/v, 7 days). C57BL/6 mice were fed one of three isocaloric diets: basal diet control (BD), or BD supplemented with 20% cooked white (WK) or dark red kidney (DK) bean flour for 3 weeks. In healthy mice, anti-inflammatory microbial-derived cecal short chain fatty acid (SCFA) levels (acetate, butyrate and propionate), colon crypt height and colonic Mucin 1 (MUC1) and Resistin-like Molecule beta (Relmβ) mRNA expression all increased in WK- and DK-fed mice compared to BD, indicative of enhanced microbial activity, gut barrier integrity and antimicrobial defense response. During colitis, both bean diets reduced (a) disease severity, (b) colonic histological damage and (c) increased mRNA expression of antimicrobial and barrier integrity-promoting genes (Toll-like Receptor 4 (TLR4), MUC1-3, Relmβ and Trefoil Factor 3 (TFF3)) and reduced proinflammatory mediator expression [interleukin (IL)-1β, IL-6, interferon (IFN)γ, tumor necrosis factor (TNF)α and monocyte chemoattractant protein-1], which correlated with reduced colon tissue protein levels. Further, bean diets exerted a systemic anti-inflammatory effect during colitis by reducing serum levels of IL-17A, IFNγ, TNFα, IL-1β and IL-6. In conclusion, both WK and DK bean-supplemented diets enhanced microbial-derived SCFA metabolite production, gut barrier integrity and the microbial defensive response in the healthy colon, which supported an anti-inflammatory phenotype during colitis. Collectively, these data demonstrate a beneficial colon-function priming effect of bean consumption that mitigates colitis severity.

  14. Sarcodon aspratus Extract Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mouse Colon and Mesenteric Lymph Nodes.

    PubMed

    Chung, Min-Yu; Hwang, Jin-Taek; Kim, Jin Hee; Shon, Dong-Hwa; Kim, Hyun-Ku

    2016-05-01

    Mushrooms have been previously investigated for their immune-modulating and anti-inflammatory properties. We examined whether the anti-inflammatory properties of Sarcodon aspratus ethanol extract (SAE) could elicit protective effects against dextran sulfate sodium (DSS)-induced colitis in vivo. Male C57/BL6 mice were randomly assigned to 1 of 4 treatment groups: control (CON; n = 8), DSS-treated (DSS; n = 9), DSS+SAE at 50 mg/kg BW (SAE50; n = 8), and DSS+SAE at 200 mg/kg BW groups (SAE200; n = 9). DSS treatment induced significant weight loss, which was significantly recovered by SAE200. Although SAE did not affect DSS-mediated reductions in colon length, it improved diarrhea and rectal bleeding induced by DSS. SAE at 200 mg/kg BW significantly attenuated IL-6 and enhanced IL-10 expression in mesenteric lymph nodes (MLN), and significantly reduced IL-6 levels in splenocytes. SAE200 also significantly attenuated DSS-induced increase in IL-6 and IL-1β, and reductions in IL-10 in colon tissue. High levels of SAE were also observed to significantly decrease inflammatory COX-2 expression that was upregulated by DSS in mice colon. These findings may have relevance for novel therapeutic strategies to mitigate inflammatory bowel disease-relevant inflammatory responses, via the direct and indirect anti-inflammatory activity of SAE. We also found that SAE harbors significant quantities of total fiber and β-glucan, suggesting a possible role for these components in protection against DSS-mediated colitis. PMID:27074537

  15. Peptidoglycan recognition protein 3 and Nod2 synergistically protect mice from dextran sodium sulfate-induced colitis

    PubMed Central

    Jing, Xuefang; Zulfiqar, Fareeha; Park, Shin Yong; Núñez, Gabriel; Dziarski, Roman; Gupta, Dipika

    2014-01-01

    Aberrant immune response and changes in the gut microflora are the main causes of inflammatory bowel disease (IBD). Peptidoglycan recognition proteins (Pglyrp1, Pglyrp2, Pglyrp3, and Pglyrp4) are bactericidal innate immunity proteins that maintain normal gut microbiome, protect against experimental colitis, and are associated with inflammatory bowel disease in humans. Nod2 is an intracellular bacterial sensor and may be required for maintaining normal gut microbiome. Mutations in Nod2 are strongly associated with Crohn's disease, but the causative mechanism is not understood, and Nod2 role in ulcerative colitis is not known. Because IBD is likely caused by variable multiple mutations in different individuals, in this study we examined the combined role of Pglyrp3 and Nod2 in the development of experimental colitis in mice. We demonstrate that a combined deficiency of Pglyrp3 and Nod2 results in higher sensitivity to dextran sodium sulfate (DSS)-induced colitis compared with a single deficiency. Pglyrp3−/−Nod2−/− mice had decreased survival and higher loss of body weight, increased intestinal bleeding, higher apoptosis of colonic mucosa, elevated expression of cytokines and chemokines, altered gut microbiome, and increased levels of ATP in the colon. Increased sensitivity to DSS-induced colitis in Pglyrp3−/−Nod2−/− mice depended on increased apoptosis of intestinal epithelium, changed gut microflora, and elevated ATP. Pglyrp3 deficiency contributed colitispredisposing intestinal microflora and increased intestinal ATP, whereas Nod2 deficiency contributed higher apoptosis and responsiveness to increased level of ATP. In summary, Pglyrp3 and Nod2 are both required for maintaining gut homeostasis and protection against colitis, but their protective mechanisms differ. PMID:25114103

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

    PubMed

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

    2007-09-01

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

  17. White and dark kidney beans reduce colonic mucosal damage and inflammation in response to dextran sodium sulfate.

    PubMed

    Monk, Jennifer M; Zhang, Claire P; Wu, Wenqing; Zarepoor, Leila; Lu, Jenifer T; Liu, Ronghua; Pauls, K Peter; Wood, Geoffrey A; Tsao, Rong; Robinson, Lindsay E; Power, Krista A

    2015-07-01

    Common beans are a rich source of nondigestible fermentable components and phenolic compounds that have anti-inflammatory effects. We assessed the gut-health-promoting potential of kidney beans in healthy mice and their ability to attenuate colonic inflammation following dextran sodium sulphate (DSS) exposure (via drinking water, 2% DSS w/v, 7 days). C57BL/6 mice were fed one of three isocaloric diets: basal diet control (BD), or BD supplemented with 20% cooked white (WK) or dark red kidney (DK) bean flour for 3 weeks. In healthy mice, anti-inflammatory microbial-derived cecal short chain fatty acid (SCFA) levels (acetate, butyrate and propionate), colon crypt height and colonic Mucin 1 (MUC1) and Resistin-like Molecule beta (Relmβ) mRNA expression all increased in WK- and DK-fed mice compared to BD, indicative of enhanced microbial activity, gut barrier integrity and antimicrobial defense response. During colitis, both bean diets reduced (a) disease severity, (b) colonic histological damage and (c) increased mRNA expression of antimicrobial and barrier integrity-promoting genes (Toll-like Receptor 4 (TLR4), MUC1-3, Relmβ and Trefoil Factor 3 (TFF3)) and reduced proinflammatory mediator expression [interleukin (IL)-1β, IL-6, interferon (IFN)γ, tumor necrosis factor (TNF)α and monocyte chemoattractant protein-1], which correlated with reduced colon tissue protein levels. Further, bean diets exerted a systemic anti-inflammatory effect during colitis by reducing serum levels of IL-17A, IFNγ, TNFα, IL-1β and IL-6. In conclusion, both WK and DK bean-supplemented diets enhanced microbial-derived SCFA metabolite production, gut barrier integrity and the microbial defensive response in the healthy colon, which supported an anti-inflammatory phenotype during colitis. Collectively, these data demonstrate a beneficial colon-function priming effect of bean consumption that mitigates colitis severity. PMID:25841250

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

    PubMed

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

    2015-01-01

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

  19. MicroRNA-155 deletion promotes tumorigenesis in the azoxymethane-dextran sulfate sodium model of colon cancer.

    PubMed

    Velázquez, Kandy T; Enos, Reilly T; McClellan, Jamie L; Cranford, Taryn L; Chatzistamou, Ioulia; Singh, Udai P; Nagarkatti, Mitzi; Nagarkatti, Prakash S; Fan, Daping; Murphy, E Angela

    2016-03-15

    Clinical studies have linked microRNA-155 (miR-155) expression in the tumor microenvironment to poor prognosis. However, whether miR-155 upregulation is predictive of a pro- or antitumorigenic response is unclear, as the limited preclinical data available remain controversial. We examined miR-155 expression in tumor tissue from colon cancer patients. Furthermore, we investigated the role of this microRNA in proliferation and apoptosis, inflammatory processes, immune cell populations, and transforming growth factor-β/SMAD signaling in a chemically induced (azoxymethane-dextran sulfate sodium) mouse model of colitis-associated colon cancer. We found a higher expression of miR-155 in the tumor region than in nontumor colon tissue of patients with colon cancer. Deletion of miR-155 in mice resulted in a greater number of polyps/adenomas, an increased symptom severity score, a higher grade of epithelial dysplasia, and a decrease in survival. Surprisingly, these findings were associated with an increase in apoptosis in the normal mucosa, but there was no change in proliferation. The protumorigenic effects of miR-155 deletion do not appear to be driven solely by dysregulation of inflammation, as both genotypes had relatively similar levels of inflammatory mediators. The enhanced tumorigenic response in miR-155(-/-) mice was associated with alterations in macrophages and neutrophils, as markers for these populations were decreased and increased, respectively. Furthermore, we demonstrated a greater activation of the transforming growth factor-β/SMAD pathway in miR-155(-/-) mice, which was correlated with the increased tumorigenesis. Given the multiple targets of miR-155, careful evaluation of its role in tumorigenesis is necessary prior to any consideration of its potential as a biomarker and/or therapeutic target in colon cancer.

  20. A cheese-containing diet modulates immune responses and alleviates dextran sodium sulfate-induced colitis in mice.

    PubMed

    Hosoya, T; Ogawa, A; Sakai, F; Kadooka, Y

    2012-06-01

    Diet has a significant effect on immune and inflammatory responses. To date, no studies have described how consumption of a diet containing a relatively high amount of cheese affects immune responses and the inflammatory status of the body. We examined these responses in normal mice and mice with dextran sodium sulfate (DSS)-induced colitis associated with increased inflammatory responses, using a diet containing approximately 44% of a whole cheese powder and a diet containing casein, lard, and corn oil as the control. In normal mice, consumption of the cheese-containing diet induced regulatory T cells (T(reg)), which regulate immune and inflammatory responses, and suppressed the production of IL-17, IL-4, and IL-10 in Peyer's patch cells from the intestine. The T(reg) population and cytokine production were not altered in spleen cells. In mice with DSS-induced colitis, consumption of the cheese-containing diet alleviated the symptoms of colitis, as evidenced by prevention of body weight loss and colon length shortening, and inhibition of an increase in the disease activity index, which includes diarrhea and fecal bleeding. This relief of clinical symptoms was also associated with decreased production of proinflammatory cytokines (IL-17 and IL-6) and increased production of the antiinflammatory cytokine transforming growth factor-β1 in Peyer's patch cells. The T(reg) population was reduced by consumption of the cheese-containing diet in Peyer's patch cells and spleen cells, which might reflect the alleviated symptoms of colitis. Consumption of the cheese-containing diet compared with the control diet enhanced antiinflammatory and immune regulatory responses in normal mice and in a DSS-colitis mouse model. PMID:22612918

  1. Sarcodon aspratus Extract Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mouse Colon and Mesenteric Lymph Nodes.

    PubMed

    Chung, Min-Yu; Hwang, Jin-Taek; Kim, Jin Hee; Shon, Dong-Hwa; Kim, Hyun-Ku

    2016-05-01

    Mushrooms have been previously investigated for their immune-modulating and anti-inflammatory properties. We examined whether the anti-inflammatory properties of Sarcodon aspratus ethanol extract (SAE) could elicit protective effects against dextran sulfate sodium (DSS)-induced colitis in vivo. Male C57/BL6 mice were randomly assigned to 1 of 4 treatment groups: control (CON; n = 8), DSS-treated (DSS; n = 9), DSS+SAE at 50 mg/kg BW (SAE50; n = 8), and DSS+SAE at 200 mg/kg BW groups (SAE200; n = 9). DSS treatment induced significant weight loss, which was significantly recovered by SAE200. Although SAE did not affect DSS-mediated reductions in colon length, it improved diarrhea and rectal bleeding induced by DSS. SAE at 200 mg/kg BW significantly attenuated IL-6 and enhanced IL-10 expression in mesenteric lymph nodes (MLN), and significantly reduced IL-6 levels in splenocytes. SAE200 also significantly attenuated DSS-induced increase in IL-6 and IL-1β, and reductions in IL-10 in colon tissue. High levels of SAE were also observed to significantly decrease inflammatory COX-2 expression that was upregulated by DSS in mice colon. These findings may have relevance for novel therapeutic strategies to mitigate inflammatory bowel disease-relevant inflammatory responses, via the direct and indirect anti-inflammatory activity of SAE. We also found that SAE harbors significant quantities of total fiber and β-glucan, suggesting a possible role for these components in protection against DSS-mediated colitis.

  2. 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. PMID:27033117

  3. The Sasa quelpaertensis Leaf Extract Inhibits the Dextran Sulfate Sodium-induced Mouse Colitis Through Modulation of Antioxidant Enzyme Expression

    PubMed Central

    Yeom, Yiseul; Kim, Yuri

    2015-01-01

    Background: Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease. The objective of this study is to investigate the protective effect of Sasa quelpaertensis leaf extract (SQE) against oxidative stress in mice with dextran sulfate sodium (DSS)-induced colitis. Methods: Mice were treated with SQE (100 mg/kg or 300 mg/kg body weight) by gavage in advance two weeks before inflammation was induced. Then, the mice were administered with 2.5% DSS in drinking water for 7 days and normal drinking water for 7 days between two DSS treatment. Disease activity index values, gut motility, and severity of the resulting oxidative DNA damage were analyzed. The antioxidant effect of SQE was evaluated by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) activity in plasma samples. Catalase activity and expressions levels of glutathione peroxidase 1 (Gpx1), SOD1, and SOD2 were also detected in colon tissues. Results: Administration of SQE significantly reduced the severity of DSS-induced colitis compared to the control (Ctrl) group. Levels of 8-oxo-dG, an oxidative DNA damage marker, were significantly lower in the SQE group compared to the untreated DSS Ctrl group. In the SQE (300 mg/kg) group, MDA levels were significantly lower, while SOD and catalase activity levels in the plasma samples were significantly higher compared with the DSS Ctrl group. The expression levels of the antioxidant enzymes, SOD2 and Gpx1, were significantly higher, while the levels of SOD 1 expression were lower, in the colon tissues of the DSS Ctrl group compared with those of the Ctrl group. In contrast, administration of SQE significantly down-regulated SOD2 and Gpx1 expressions and up-regulated SOD1 expression. Conclusions: These results indicate that SQE efficiently suppresses oxidative stress in DSS-induced colitis in mice, and its action is associated with the regulation of antioxidant enzymes. PMID:26151047

  4. 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

  5. Effects of early life dextran sulfate sodium administration on pathology and immune response in broilers and layers.

    PubMed

    Simon, K; Arts, J A J; de Vries Reilingh, G; Kemp, B; Lammers, A

    2016-07-01

    Intestinal pathology early in life may affect immune development and therefore immune responses later in life. Dextran sulfate sodium (DSS) induces colitis in rodents and is a widely used model for inflammatory bowel diseases. The present study investigated DSS as a model for early life intestinal pathology and its consequences on intestinal pathology, ileal cytokine, and immunoglobulin mRNA expression levels as well as the antibody response towards an immunological challenge later in life in chickens. Broiler and layer chicks received 2.5% DSS in drinking water during d 11 through d 18 post hatch or plain drinking water as a control. As an immunological challenge all birds received a combination of Escherichia coli lipopolysaccharide (LPS) and human serum albumin (HuSA) intramuscularly (i.m.) at d 35, and antibody titers against LPS, HuSA, and keyhole limpet hemocyanin (KLH) were determined to investigate effects of intestinal inflammation early in life on humoral immunity later in life. DSS treated birds showed a decrease in BW from which broilers quickly recovered, but which persisted for several weeks in layers. Histological examination of intestinal samples showed symptoms similar to those in rodents, including shortening and loss of villi and crypts as well as damage of the epithelial cell layer of different parts of the intestine. Effects of DSS on intestinal morphology were less severe in broilers that also showed a lower mortality in response to DSS than layers. No effect of DSS on ileal cytokine expression levels could be observed, but ileal immunoglobulin expression levels were decreased in DSS treated broilers that also showed lower antibody titers against LPS in response to the challenge. In conclusion, DSS may serve as a model for intestinal pathology early in life, although more research on the appropriate dose is necessary and is likely to differ between breeds. Results from the present study could indicate that broilers are less susceptible to DSS

  6. Colorimetry and constant-potential coulometry determinations of transferrin-bound iron, total iron-binding capacity, and total iron in serum containing iron-dextran, with use of sodium dithionite and alumina columns.

    PubMed

    Jacobs, J C; Alexander, N M

    1990-10-01

    After the parenteral administration of iron-dextran (imferon), the increased total iron concentrations in serum can be determined by atomic absorption spectroscopy and by colorimetric methods involving sodium dithionite, which reductively dissociates iron from the dextran complex. We report that constant-potential coulometry detects only about 55-70% of dextran-bound iron before dithionite reduction and variable amounts after reaction with the reducing agent. In addition, we have developed a procedure for determining transferrin-bound iron, total iron-binding capacity (TIBC), total iron, and dextran-bound iron with the Kodak Ektachem colorimetric system. In determining total serum iron, the sample is first mixed with sodium dithionite, which rapidly dissociates all dextran-bound iron, but does not remove iron from either transferrin or hemoglobin. After the mixture is applied to an Ektachem slide, transferrin-bound iron is released at pH 4 and is detected together with the iron previously bound to dextran. TIBC is determined by mixing serum with ferric citrate in moderate excess and filtering through a small alumina (Al2O3) column, which binds excess free iron and iron-dextran; the iron in the column eluate represents the TIBC. Transferrin-bound iron is determined by applying diluted serum without added ferric citrate to an alumina column and measuring the iron in the column eluate. Dextran-bound iron is equivalent to the difference between total and transferrin-bound iron. Using this method, we found that transferrin iron-binding sites are saturated in vitro by excess iron-dextran less efficiently than by ferric citrate.

  7. Anti-inflammatory Actions of (+)-3'α-Angeloxy-4'-keto-3',4'-dihydroseselin (Pd-Ib) against Dextran Sulfate Sodium-Induced Colitis in C57BL/6 Mice.

    PubMed

    Mu, Huai-Xue; Liu, Jing; Fatima, Sarwat; Lin, Cheng-Yuan; Shi, Xiao-Ke; Du, Bin; Xiao, Hai-Tao; Fan, Bao-Min; Bian, Zhao-Xiang

    2016-04-22

    The immunoregulatory protective properties of (+)-3'α-angeloxy-4'-keto-3',4'-dihydroseselin (Pd-Ib) isolated from Bupleurum malconense has not been reported. In the present study, the therapeutic effect of Pd-Ib (30, 60, and 120 mg/kg/day) was examined in a mouse model of dextran sulfate sodium (DSS)-induced acute colitis. Administration of Pd-Ib significantly reduced the disease activity index, inhibited the shortening of colon length, reduced colonic tissue damage, and suppressed colonic myeloperoxidase activity and nitric oxide levels in mice with DSS-induced colitis. Moreover, Pd-Ib greatly suppressed the secretion of pro-inflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-17A while enhancing the level of anti-inflammatory cytokine IL-4. The protein levels of phosphorylated STAT3 (p-STAT3) and phosphorylated p38 (p-p38) were down-regulated in the colonic tissues of DSS-treated mice. Importantly, the anti-inflammatory effect of Pd-Ib against acute colitis was comparable to the anti-inflammatory sulfa drug sulfasalazine (300 mg/kg). Furthermore, the in vitro study showed that the inhibitory effect of Pd-Ib on p-STAT3 and IL-6 protein levels was accompanied by the reduction of MAPKs (JNK and p38). In conclusion, this study suggested that Pd-Ib attenuated DSS-induced acute colitis via the regulation of interleukins principally through the STAT3 and MAPK pathways.

  8. 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

  9. 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

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

    PubMed

    Chen, Xi; Liu, Xi-shuang

    2016-03-01

    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.

  11. Differential acute effects of selenomethionine and sodium selenite on the severity of colitis.

    PubMed

    Hiller, Franziska; Oldorff, Lisa; Besselt, Karolin; Kipp, Anna Patricia

    2015-04-01

    The European population is only suboptimally supplied with the essential trace element selenium. Such a selenium status is supposed to worsen colitis while colitis-suppressive effects were observed with adequate or supplemented amounts of both organic selenomethionine (SeMet) and inorganic sodium selenite. In order to better understand the effect of these selenocompounds on colitis development we examined colonic phenotypes of mice fed supplemented diets before the onset of colitis or during the acute phase. Colitis was induced by treating mice with 1% dextran sulfate sodium (DSS) for seven days. The selenium-enriched diets were either provided directly after weaning (long-term) or were given to mice with a suboptimal selenium status after DSS withdrawal (short-term). While long-term selenium supplementation had no effect on colitis development, short-term selenite supplementation, however, resulted in a more severe colitis. Colonic selenoprotein expression was maximized in all selenium-supplemented groups independent of the selenocompound or intervention time. This indicates that the short-term selenite effect appears to be independent from colonic selenoprotein expression. In conclusion, a selenite supplementation during acute colitis has no health benefits but may even aggravate the course of disease. PMID:25867950

  12. Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis.

    PubMed

    Vieira, Erica L M; Leonel, Alda J; Sad, Alexandre P; Beltrão, Nathália R M; Costa, Thaís F; Ferreira, Talita M R; Gomes-Santos, Ana C; Faria, Ana M C; Peluzio, Maria C G; Cara, Denise C; Alvarez-Leite, Jacqueline I

    2012-05-01

    Butyrate is a four-carbon short-chain fatty acid that improves colonic trophism. Although several studies have shown the benefits of butyrate enemas in ulcerative colitis (UC), studies using the oral route are rare in the literature. In the present study, we evaluated the effect of butyrate intake in the immune response associated to UC. For that, mice were fed control or butyrate (0.5% sodium butyrate) diets for 14 days. Acute UC was induced by dextran sulphate sodium (DSS, 2.5%), replacing drinking water. The results showed that, in UC animals, oral butyrate significantly improved trophism and reduced leukocyte (eosinophil and neutrophil) infiltration in the colon mucosa and improved the inflammatory profile (activated macrophage, B and T lymphocytes) in cecal lymph nodes. In the small intestine, although mucosa histology was similar among groups, DSS treatment reduced duodenal transforming growth factor-β, increased interleukin-10 concentrations and increased memory T lymphocytes and dendritic cells in Peyer's patches. Butyrate supplementation was able to revert these alterations. When cecal butyrate concentration was analyzed in cecal content, it was still higher in the healthy animals receiving butyrate than in the UC+butyrate and control groups. In conclusion, our results show that oral administration of sodium butyrate improves mucosa lesion and attenuates the inflammatory profile of intestinal mucosa, local draining lymph nodes and Peyer's patches of DSS-induced UC. Our results also highlight the potential use of butyrate supplements as adjuvant in UC treatment.

  13. The effect of hypertonic saline dextran solutions on hypoxic pulmonary vasoconstriction in anaesthetised piglets.

    PubMed

    Bellezza, M; Kerbaul, F; Roussel, L; Imbert, M; Guidon, C

    2002-10-01

    Hypoxic pulmonary vasoconstriction (HPV) is a regulatory mechanism by which blood is diverted from poorly ventilated to better ventilated areas of the lung. The aim of the present study was to assess the extent to which hypertonic saline dextran and dextran solutions modify the magnitude of HPV during isovolumic haemodilution in intact acutely instrumented piglets. Eighteen large white piglets were anesthetised and assigned to two groups. Mean pulmonary arterial pressure (PAP) and cardiac output (Q), systemic arterial pressure and left arterial pressure (LAP) were measured. A decrease in Q was obtained by reducing venous return. This enabled measurement of transpulmonary pressures (mean PAP minus LAP) at four levels of Q in hyperoxia (inspiratory oxygen fraction (FiO2)=0.4) then in hypoxia (Fi,O2=0.1) in the two groups before blood soustraction (10 mL x kg(-1)) and after loading with sodium chloride (NaCl) 7.5% and dextran 6% or with dextran 6% alone. Dextran alone led to a decrease in mean PAP-LAP/Q values, and NaCl with dextran was associated with a significant shift of mean PAP-LAP/Q plots to higher pressures in hypoxia. Hypertonic saline dextran solution, as replacement fluid in isovolaemic haemodilution increased the magnitude of hypoxic pulmonary vasoconstriction, whereas dextran solution reduced it.

  14. Interrelationship between partition behavior of organic compounds and proteins in aqueous dextran-polyethylene glycol and polyethylene glycol-sodium sulfate two-phase systems.

    PubMed

    Ferreira, Luisa A; da Silva, Nuno R; Wlodarczyk, Samarina R; Loureiro, Joana A; Madeira, Pedro P; Teixeira, José A; Uversky, Vladimir N; Zaslavsky, Boris Y

    2016-04-22

    Partition behavior of adenosine and guanine mononucleotides was examined in aqueous dextran-polyethylene glycol (PEG) and PEG-sodium sulfate two-phase systems. The partition coefficients for each series of mononucleotides were analyzed as a functions of the number of phosphate groups and found to be dependent on the nature of nucleic base and on the type of ATPS utilized. It was concluded that an average contribution of a phosphate group into logarithm of partition coefficient of a mononucleotide cannot be used to estimate the difference between the electrostatic properties of the coexisting phases of ATPS. The data obtained in this study were considered together with those for other organic compounds and proteins reported previously, and the linear interrelationship between logarithms of partition coefficients in dextran-PEG, PEG-Na2SO4 and PEG-Na2SO4-0.215M NaCl (all in 0.01M Na- or K/Na-phosphate buffer, pH 7.4 or 6.8) was established. Similar relationship was found for the previously reported data for proteins in Dex-PEG, PEG-600-Na2SO4, and PEG-8000-Na2SO4 ATPS. It is suggested that the linear relationships of the kind established in ATPS may be observed for biological properties of compounds as well. PMID:27016118

  15. Interrelationship between partition behavior of organic compounds and proteins in aqueous dextran-polyethylene glycol and polyethylene glycol-sodium sulfate two-phase systems.

    PubMed

    Ferreira, Luisa A; da Silva, Nuno R; Wlodarczyk, Samarina R; Loureiro, Joana A; Madeira, Pedro P; Teixeira, José A; Uversky, Vladimir N; Zaslavsky, Boris Y

    2016-04-22

    Partition behavior of adenosine and guanine mononucleotides was examined in aqueous dextran-polyethylene glycol (PEG) and PEG-sodium sulfate two-phase systems. The partition coefficients for each series of mononucleotides were analyzed as a functions of the number of phosphate groups and found to be dependent on the nature of nucleic base and on the type of ATPS utilized. It was concluded that an average contribution of a phosphate group into logarithm of partition coefficient of a mononucleotide cannot be used to estimate the difference between the electrostatic properties of the coexisting phases of ATPS. The data obtained in this study were considered together with those for other organic compounds and proteins reported previously, and the linear interrelationship between logarithms of partition coefficients in dextran-PEG, PEG-Na2SO4 and PEG-Na2SO4-0.215M NaCl (all in 0.01M Na- or K/Na-phosphate buffer, pH 7.4 or 6.8) was established. Similar relationship was found for the previously reported data for proteins in Dex-PEG, PEG-600-Na2SO4, and PEG-8000-Na2SO4 ATPS. It is suggested that the linear relationships of the kind established in ATPS may be observed for biological properties of compounds as well.

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

    PubMed Central

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

    2013-01-01

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

  17. Dimethyl fumarate ameliorates dextran sulfate sodium-induced murine experimental colitis by activating Nrf2 and suppressing NLRP3 inflammasome activation.

    PubMed

    Liu, Xiuting; Zhou, Wei; Zhang, Xin; Lu, Ping; Du, Qianming; Tao, Lei; Ding, Yang; Wang, Yajing; Hu, Rong

    2016-07-15

    In the present study, we examined the effects of dimethyl fumarate (DMF) on dextran sulfate sodium (DSS)-induced murine colitis, an animal model which mimics human IBD. Oral administration of DMF dose-dependently attenuated body weight loss, colon length shortening and colonic pathological damage including decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities in DSS-treated mice. Increased glutathione (GSH) induced by DMF demonstrated its potential antioxidant capacity. In addition, Nrf2 and its downstream genes were markedly activated by DMF. Furthermore, protein and mRNA levels of pro-inflammatory cytokines, including IL-1β, TNF-α and IL-6 were markedly suppressed by DMF. At the same time, decreased activation of caspase-1 was detected in DMF-treated mice, indicating that the NLRP3 inflammasome activation was suppressed. The in vitro study verified a negative regulation of DMF and its intestinal metabolite on NLRP3 inflammasome. Moreover, the inhibitory effect was found to be mostly dependent on Nrf2 which decreased mitochondrial ROS (mROS) generation and mitochondrial DNA (mtDNA) release. Taken together, our results demonstrated the ability of DMF to inhibit NLRP3 inflammasome activation and its potential use in the treatment of NLRP3-associated diseases. PMID:27184504

  18. Arvelexin inhibits colonic inflammation by suppression of NF-κB activation in dextran sulfate sodium-induced mice and TNF-α-induced colonic epithelial cells.

    PubMed

    Cho, Eu-Jin; Shin, Ji-Sun; Chung, Kyung-Sook; Lee, Yong Sup; Cho, Young-Wuk; Baek, Nam-In; Chung, Hae-Gon; Lee, Kyung-Tae

    2012-08-01

    Recently, we reported the anti-inflammatory effects of arvelexin isolated from Brassica rapa in macrophages. In the present study, the effects of arvelexin were investigated in a dextran sulfate sodium (DSS)-induced colitis mouse model and in a cellular model. In the DSS-induced colitis model, arvelexin significantly reduced the severity of colitis, as assessed by disease activity, colonic damage, neutrophil infiltration, and levels of colonic iNOS. Moreover, arvelexin inhibited the expressions of IL-8, IP-10, ICAM-1, and VCAM-1 in HT-29 colonic epithelial cells. Arvelexin also inhibited the TNF-α-induced adhesion of U937 monocytic cells to HT-29 cells. Furthermore, arvelexin reduced p65 NF-κB subunit translocation to the nucleus and IκBα degradation in the colonic tissues and in TNF-α-induced HT-29 cells. These results demonstrate that the ameliorative effects of arvelexin on colonic injury are mainly related to its ability to inhibit the inflammatory responses via NF-κB inactivation, and support its possible therapeutic role in colitis.

  19. Identification of commensal bacterial strains that modulate Yersinia enterocolitica and dextran sodium sulfate-induced inflammatory responses: implications for the development of probiotics.

    PubMed

    Frick, Julia S; Fink, Kerstin; Kahl, Frauke; Niemiec, Maria J; Quitadamo, Matteo; Schenk, Katrin; Autenrieth, Ingo B

    2007-07-01

    An increasing body of evidence suggests that probiotic bacteria are effective in the treatment of enteric infections, although the molecular basis of this activity remains elusive. To identify putative probiotics, we tested commensal bacteria in terms of their toxicity, invasiveness, inhibition of Yersinia-induced inflammation in vitro and in vivo, and modulation of dextran sodium sulfate (DSS)-induced colitis in mice. The commensal bacteria Escherichia coli, Bifidobacterium adolescentis, Bacteroides vulgatus, Bacteroides distasonis, and Streptococcus salivarius were screened for adhesion to, invasion of, and toxicity for host epithelial cells (EC), and the strains were tested for their ability to inhibit Y. enterocolitica-induced NF-kappaB activation. Additionally, B. adolescentis was administered to mice orally infected with Y. enterocolitica and to mice with mucosae impaired by DSS treatment. None of the commensal bacteria tested was toxic for or invaded the EC. B. adolescentis, B. distasonis, B. vulgatus, and S. salivarius inhibited the Y. enterocolitica-induced NF-kappaB activation and interleukin-8 production in EC. In line with these findings, B. adolescentis-fed mice had significantly lower results for mean pathogen burden in the visceral organs, intestinal tumor necrosis factor alpha mRNA expression, and loss of body weight upon oral infection with Y. enterocolitica. In addition, the administration of B. adolescentis decelerated inflammation upon DSS treatment in mice. We suggest that our approach might help to identify new probiotics to be used for the treatment of inflammatory and infectious gastrointestinal disorders.

  20. Involvement of stimulation of α7 nicotinic acetylcholine receptors in the suppressive effect of tropisetron on dextran sulfate sodium-induced colitis in mice.

    PubMed

    Tasaka, Yuichi; Yasunaga, Daiki; Kiyoi, Takeshi; Tanaka, Mamoru; Tanaka, Akihiro; Suemaru, Katsuya; Araki, Hiroaki

    2015-03-01

    Ulcerative colitis (UC) involves chronic inflammation of the large intestine. Several agents are used to treat UC, but adverse side effects are remaining problems. We examined the effect of tropisetron as a new type of drug for UC using a dextran sulfate sodium (DSS)-induced model of colitis in mice. We developed a DSS-induced model of colitis and calculated the Disease Activity Index and colon length. We measured myeloperoxidase activity and determined the protein level and mRNA level of cytokines in the colon. DSS-induced colitis was ameliorated by administration of tropisetron and PNU282987. Pre-administration of methyllycaconitine diminished the suppressive effect of tropisetron upon DSS-induced colitis. These findings suggested that α7 nicotinic acetylcholine receptors (α7 nAChRs) were related to the suppressive effect of tropisetron on DSS-induced colitis. Additionally, stimulation of α7 nAChRs decreased the colon level of interleukin-6 and interferon-γ upon DSS administration. Furthermore, stimulation of α7 nAChRs decreased macrophage infiltration, with expression of α7 nAChR increased by DSS administration. These results suggest that the underlying mechanism of this suppressive effect on DSS-induced colitis is via stimulation of α7 nAChRs and involves suppression of expression of pro-inflammatory cytokines. Tropisetron could be a new type of therapeutic agent for UC.

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

    PubMed

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

    2015-11-01

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

  2. 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.

  3. A Probiotic Preparation Duolac-Gold Ameliorates Dextran Sulphate Sodium-induced Mouse Colitis by Downregulating the Expression of IL-6

    PubMed Central

    Yoon, Hyunho; Yoon, Yeo-Sang; Kim, Min-Soo; Chung, Myung-Jun

    2014-01-01

    Probiotics are live microorganisms that confer a health benefit on the host. Duolac-Gold is a mixture of seven probiotic bacteria containing three species of Bifidobacteria, two species of Lactobacillus, and Streptococcus thermophilus. The aim of this study was to assess the anti-inflammatory effects of Duolac-Gold in an inflammatory bowel disease (IBD) mouse model. IBD was induced by administering 1.5% dextran sulfate sodium (DSS) for 10 days. After induction of DSS-induced colitis, Duolac-Gold was orally administered at three different concentrations. Interestingly, Duolac-Gold treatment accelerated IBD healing, and anti-inflammatory activity was assessed by weight loss, length of the colon, and a microscopic damage score by histology. The expression of inflammatory related cytokines was measured in colon tissues and serum. Of these cytokines, the expression of interleukin-6 decreased remarkably after Duolac-Gold treatment. Taken together, these results suggest that Duolac-Gold treatment is effective in IBD healing by regulating IL-6. PMID:24795796

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

    PubMed

    Okazaki, Yukako; Chiji, Hideyuki; Kato, Norihisa

    2016-01-01

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

  5. 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. PMID:27481492

  6. Acetylsalicylic Acid reduces the severity of dextran sodium sulfate-induced colitis and increases the formation of anti-inflammatory lipid mediators.

    PubMed

    Köhnke, Thomas; Gomolka, Beate; Bilal, Süleyman; Zhou, Xiangzhi; Sun, Yanping; Rothe, Michael; Baumgart, Daniel C; Weylandt, Karsten H

    2013-01-01

    The role of non-steroidal anti-inflammatory drugs in inflammatory bowel disease is controversial, as they have been implicated in disease aggravation. Different from other cyclooxygenase inhibitors, acetylsalicylic acid (ASA) enhances the formation of anti-inflammatory and proresolution lipoxins derived from arachidonic acid as well as resolvins from omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). In this study, we examined the effect of ASA on murine dextran sodium sulfate colitis. A mouse magnetic resonance imaging (MRI) protocol and post mortem assessment were used to assess disease severity, and lipid metabolites were measured using liquid chromatography-coupled tandem mass spectrometry. Decreased colitis activity was demonstrated by phenotype and MRI assessment in mice treated with ASA, and confirmed in postmortem analysis. Analysis of lipid mediators showed sustained formation of lipoxin A4 and an increase of DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA) after treatment with ASA. Furthermore, in vitro experiments in RAW264.7 murine macrophages demonstrated significantly increased phagocytosis activity after incubation with 17-HDHA, supporting its proresolution effect. These results show a protective effect of ASA in a murine colitis model and could give a rationale for a careful reassessment of ASA therapy in patients with inflammatory bowel disease and particularly ulcerative colitis, possibly combined with DHA supplementation.

  7. 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. PMID:27223481

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-03-01

    The microbiota affects host health, and dysbiosis is involved in colitis. Sorghum bran influences butyrate concentrations during dextran sodium sulfate (DSS) colitis, suggesting microbiota changes. We aimed to characterize the microbiota during colitis, and ascertain if polyphenol-rich sorghum bran diets mitigate these effects. Rats (n = 80) were fed diets containing 6% fiber from cellulose, or Black (3-deoxyanthocyanins), Sumac (condensed tannins), or Hi Tannin black (both) sorghum bran. Inflammation was induced three times using 3% DSS for 48 h (40 rats, 2 week separation), and the microbiota characterized by pyrosequencing. The Firmicutes/Bacteroidetes ratio was higher in Cellulose DSS rats. Colonic injury negatively correlated with Firmicutes, Actinobacteria, Lactobacillales and Lactobacillus, and positively correlated with Unknown/Unclassified. Post DSS#2, richness was significantly lower in Sumac and Hi Tannin black. Post DSS#3 Bacteroidales, Bacteroides, Clostridiales, Lactobacillales and Lactobacillus were reduced, with no Clostridium identified. Diet significantly affected Bacteroidales, Bacteroides, Clostridiales and Lactobacillus post DSS#2 and #3. Post DSS#3 diet significantly affected all genus, including Bacteroides and Lactobacillus, and diversity and richness increased. Sumac and Hi Tannin black DSS had significantly higher richness compared to controls. Thus, these sorghum brans may protect against alterations observed during colitis including reduced microbial diversity and richness, and dysbiosis of Firmicutes/Bacteroidetes. PMID:25764457

  10. Orally administered lactoperoxidase ameliorates dextran sulfate sodium-induced colitis in mice by up-regulating colonic interleukin-10 and maintaining peripheral regulatory T cells.

    PubMed

    Shin, Kouichirou; Horigome, Ayako; Yamauchi, Koji; Yaeshima, Tomoko; Iwatsuki, Keiji

    2009-11-01

    We previously demonstrated orally administered bovine lactoperoxidase (LPO) ameliorated dextran sulfate sodium-induced colitis in mice. Here, we examine the mechanism of action of LPO. Three days after colitis induction, expression of interferon-gamma mRNA in colonic tissue was significantly decreased in mice administered LPO; while mRNA expression of interleukin (IL)-10 and regulatory T cell (Treg) marker, Foxp3, were significantly increased. The proportion of CD4+CD25+ Tregs in peripheral CD4+ T cells was also significantly elevated when LPO was administered. Nine days after colitis induction, the severity of colitis symptoms, including body weight loss and colon shortening, was reduced and expression of IL-10 mRNA was increased in mice administered LPO. The proportion of CD4+CD25+ Tregs in peripheral leukocytes was also significantly elevated when LPO was administered. These results suggest LPO ameliorates colitis by up-regulating colonic anti-inflammatory cytokines and maintaining peripheral regulatory T cells.

  11. Dead Nano-Sized Lactobacillus plantarum Inhibits Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer in Balb/c Mice.

    PubMed

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

    2015-12-01

    The chemopreventive effects of dead nano-sized Lactobacillus plantarum (nLp) on colon carcinogenesis, induced by dextran sulfate sodium and azoxymethane, were evaluated using Balb/c mice and compared with the effects of pure live L. plantarum (pLp). nLp is a dead shrunken form of L. plantarum derived from kimchi and has a particle size of 0.5-1.0 μm. Animals fed nLp showed less weight loss, longer colons, lower colon weight/length ratios, and fewer colonic tumors compared with pLp. In addition, the administration of nLp significantly reduced the expression of inflammatory markers, mediated the expression of cell cycle and apoptotic markers in colon tissues, and elevated fecal IgA levels more than pLp. Accordingly, the present study shows that the anticolorectal cancer activities of nLp are greater than those of pLp and suggests this is due to the suppression of inflammation, the induction of cell cycle arrest and apoptosis, and enhanced IgA secretion. PMID:26595186

  12. Acetylsalicylic Acid reduces the severity of dextran sodium sulfate-induced colitis and increases the formation of anti-inflammatory lipid mediators.

    PubMed

    Köhnke, Thomas; Gomolka, Beate; Bilal, Süleyman; Zhou, Xiangzhi; Sun, Yanping; Rothe, Michael; Baumgart, Daniel C; Weylandt, Karsten H

    2013-01-01

    The role of non-steroidal anti-inflammatory drugs in inflammatory bowel disease is controversial, as they have been implicated in disease aggravation. Different from other cyclooxygenase inhibitors, acetylsalicylic acid (ASA) enhances the formation of anti-inflammatory and proresolution lipoxins derived from arachidonic acid as well as resolvins from omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). In this study, we examined the effect of ASA on murine dextran sodium sulfate colitis. A mouse magnetic resonance imaging (MRI) protocol and post mortem assessment were used to assess disease severity, and lipid metabolites were measured using liquid chromatography-coupled tandem mass spectrometry. Decreased colitis activity was demonstrated by phenotype and MRI assessment in mice treated with ASA, and confirmed in postmortem analysis. Analysis of lipid mediators showed sustained formation of lipoxin A4 and an increase of DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA) after treatment with ASA. Furthermore, in vitro experiments in RAW264.7 murine macrophages demonstrated significantly increased phagocytosis activity after incubation with 17-HDHA, supporting its proresolution effect. These results show a protective effect of ASA in a murine colitis model and could give a rationale for a careful reassessment of ASA therapy in patients with inflammatory bowel disease and particularly ulcerative colitis, possibly combined with DHA supplementation. PMID:24083240

  13. Inhibitory effects of Dendrobium candidum Wall ex Lindl. on azoxymethane- and dextran sulfate sodium-induced colon carcinogenesis in C57BL/6 mice

    PubMed Central

    WANG, QIANG; SUN, PENG; LI, GUIJIE; ZHU, KAI; WANG, CUN; ZHAO, XIN

    2014-01-01

    Dendrobium candidum Wall ex Lindl. was purchased for the evaluation of azoxymethane (AOM)- and dextran sulfate sodium (DSS)-induced colon carcinogenesis in C57BL/6 mice. The body weights of the AOM- and DSS-induced colon cancer control groups were lighter than those of the untreated mice. D. candidum increased the body weights of the mice compared with the control group, and reduced the levels of the serum proinflammatory cytokines, IL-6, IL-12, TNF-α and IFN-γ, compared with the colon cancer control group. Reverse transcription-polymerase chain reaction and western blot analyses of the apoptotic-related genes, bax, bcl-2, caspase-3 and caspase-9, were performed in the colon tissues. The high-concentration D. candidum group showed a significant increase in the mRNA and protein expression levels of bax, caspase-3 and caspase-9 and decreased expression levels of bcl-2 compared with the control group. These results indicate that D. candidum Wall ex Lindl. exhibits preventive effects against colon carcinogenesis in mice. PMID:24396476

  14. Enterococcus durans TN-3 Induces Regulatory T Cells and Suppresses the Development of Dextran Sulfate Sodium (DSS)-Induced Experimental Colitis

    PubMed Central

    Kanda, Toshihiro; Ohno, Masashi; Imaeda, Hirotsugu; Shimada, Takashi; Inatomi, Osamu; Bamba, Shigeki; Sugimoto, Mitsushige; Andoh, Akira

    2016-01-01

    Background and Aims Probiotic properties of Enterococcus strains have been reported previously. In this study, we investigated the effects of Enterococcus (E.) durans TN-3 on the development of dextran sulfate sodium (DSS) colitis. Methods BALB/c mice were fed with 4.0% DSS in normal chow. Administration of TN-3 (10mg/day) was initiated 7days before the start of DSS feeding. Mucosal cytokine expression was analyzed by real time-PCR and immunohistochemistry. The lymphocyte subpopulation were analyzed by flow cytometry. The gut microbiota profile was analyzed by a terminal-restriction fragment length polymorphism method (T-RFLP). Results The disease activity index and histological colitis score were significantly lower in the DSS plus TN-3 group than in the DSS group. The mucosal mRNA expression of proinflammatory cytokines (IL-1β, IL-6, IL-17A and IFN-γ) decreased significantly in the DSS plus TN-3 group as compared to the DSS group. The proportion of regulatory T cells (Treg cells) in the mucosa increased significantly in the DSS plus TN-3 group as compared to the DSS group. Both fecal butyrate levels and the diversity of fecal microbial community were significantly higher in the TN-3 plus DSS group than in the DSS group. Conclusions E. durans TN-3 exerted an inhibitory effect on the development of DSS colitis. This action might be mediated by the induction of Treg cells and the restoration of the diversity of the gut microbiota. PMID:27438072

  15. Protective effects of ethanol extract from Portulaca oleracea L on dextran sulphate sodium-induced mice ulcerative colitis involving anti-inflammatory and antioxidant

    PubMed Central

    Yang, Xiaohang; Yan, Yongmei; Li, Jiankang; Tang, Zhishu; Sun, Jing; Zhang, Huan; Hao, Siyang; Wen, Aidong; Liu, Li

    2016-01-01

    Portulaca oleracea L., (POL) is one of commonly used medicine-food herbs and has a cosmopolitan distribution in many countries. Many studies showed that POL exhibited a wide range of pharmacological effects such as anti-inflammatory and liver complaints. In the clinical studies, POL was usually used for the treatment of UC disease and the clinical efficacy was well, but the mechanism and scientific intension was still unknown. In the present study, we studied the protective effects of the ethanol extract from POL on dextran sulphate sodium-induced UC in C57BL/6 mice model through oxidative stress and inflammatory pathway. The results demonstrated that the ethanol extract from POL could exhibit the effective protection for the DSS induced UC by increasing the colon length, decreasing body weight loss and the disease activity index score, inhibiting oxidative stress response through the MDA, NO, SOD activities, reducing the mRNA expressions of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and the protein expressions of TNF-α and NF-kB p65. These results may prove that POL could be considered as a useful and effective botanical compound from the edible plant to be used in UC through the oxidative stress and inflammatory activities. PMID:27347321

  16. 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.

  17. Dead Nano-Sized Lactobacillus plantarum Inhibits Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer in Balb/c Mice.

    PubMed

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

    2015-12-01

    The chemopreventive effects of dead nano-sized Lactobacillus plantarum (nLp) on colon carcinogenesis, induced by dextran sulfate sodium and azoxymethane, were evaluated using Balb/c mice and compared with the effects of pure live L. plantarum (pLp). nLp is a dead shrunken form of L. plantarum derived from kimchi and has a particle size of 0.5-1.0 μm. Animals fed nLp showed less weight loss, longer colons, lower colon weight/length ratios, and fewer colonic tumors compared with pLp. In addition, the administration of nLp significantly reduced the expression of inflammatory markers, mediated the expression of cell cycle and apoptotic markers in colon tissues, and elevated fecal IgA levels more than pLp. Accordingly, the present study shows that the anticolorectal cancer activities of nLp are greater than those of pLp and suggests this is due to the suppression of inflammation, the induction of cell cycle arrest and apoptosis, and enhanced IgA secretion.

  18. 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. PMID:25036966

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2012-08-01

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

  1. Dextran sulfate sodium-induced colitis alters stress-associated behaviour and neuropeptide gene expression in the amygdala-hippocampus network of mice.

    PubMed

    Reichmann, Florian; Hassan, Ahmed Mostafa; Farzi, Aitak; Jain, Piyush; Schuligoi, Rufina; Holzer, Peter

    2015-06-12

    Psychological stress causes disease exacerbation and relapses in inflammatory bowel disease (IBD) patients. Since studies on stress processing during visceral inflammation are lacking, we investigated the effects of experimental colitis as well as psychological stress on neurochemical and neuroendocrine changes as well as behaviour in mice. Dextran sulfate sodium (DSS)-induced colitis and water avoidance stress (WAS) were used as mouse models of colitis and mild psychological stress, respectively. We measured WAS-associated behaviour, gene expression and proinflammatory cytokine levels within the amygdala, hippocampus and hypothalamus as well as plasma levels of cytokines and corticosterone in male C57BL/6N mice. Animals with DSS-induced colitis presented with prolonged immobility during the WAS session, which was associated with brain region-dependent alterations of neuropeptide Y (NPY), NPY receptor Y1, corticotropin-releasing hormone (CRH), CRH receptor 1, brain-derived neurotrophic factor and glucocorticoid receptor gene expression. Furthermore, the combination of DSS and WAS increased interleukin-6 and growth regulated oncogene-α levels in the brain. Altered gut-brain signalling in the course of DSS-induced colitis is thought to cause the observed distinct gene expression changes in the limbic system and the aberrant molecular and behavioural stress responses. These findings provide new insights into the effects of stress during IBD.

  2. 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.

  3. Pharmacological Inhibition of Gal-3 in Mesenchymal Stem Cells Enhances Their Capacity to Promote Alternative Activation of Macrophages in Dextran Sulphate Sodium-Induced Colitis

    PubMed Central

    Simovic Markovic, Bojana; Nikolic, Aleksandar; Gazdic, Marina; Nurkovic, Jasmin; Djordjevic, Irena; Arsenijevic, Nebojsa; Stojkovic, Miodrag; Lukic, Miodrag L.; Volarevic, Vladislav

    2016-01-01

    Transplantation of mesenchymal stem cells (MSCs) reduces the severity of dextran sulphate sodium- (DSS-) induced colitis. MSCs are able to secrete Galectin-3 (Gal-3), a protein known to affect proliferation, adhesion, and migration of immune cells. We investigate whether newly synthetized inhibitor of Gal-3 (Davanat) will affect production of Gal-3 in MSCs and enhance their potential to attenuate DSS-induced colitis. Pharmacological inhibition of Gal-3 in MSCs enhances their capacity to promote alternative activation of peritoneal macrophages in vitro and in vivo. Injection of MSCs cultured in the presence of Davanat increased concentration of IL-10 in sera of DSS-treated animals and markedly enhanced presence of alternatively activated and IL-10 producing macrophages in the colons of DSS-treated mice. Pharmacological inhibition of Gal-3 in MSCs significantly attenuates concentration of Gal-3 in sera of DSS-treated animals, indicating that MSCs produce Gal-3 in this disease. In conclusion, our findings indicate that Davanat could be used for improvement of MSC-mediated polarization towards immunosuppressive M2 phenotype of macrophages. PMID:27057168

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

    PubMed

    Okazaki, Yukako; Chiji, Hideyuki; Kato, Norihisa

    2016-01-01

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

  5. 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.

  6. [Sodium dichloroisocyanurate-induced acute lung injury in a child].

    PubMed

    Wiel, E; Sicot, J; Leteurtre, S; Binoche, A; Nisse, P; Assez, N

    2013-04-01

    Intoxication, by cyanurate and its chlorated derivatives in children, is increasingly reported in the literature due to accidental ingestion compared to accidental inhalation. We report a case in a 5-year-old child who presented with acute lung injury due to accidental inhalation of gas formed after a reaction of sodium dichloroisocyanurate tablets with water. Prevention remains the best way to reduce the risk of children being intoxicated by inhalation of the gas formed after contact of tablets with water. PMID:23433843

  7. Danaparoid sodium prevents cerulein-induced acute pancreatitis in rats.

    PubMed

    Hagiwara, Satoshi; Iwasaka, Hideo; Uchida, Tomohisa; Hasegawa, Akira; Asai, Nobuhiko; Noguchi, Takayuki

    2009-07-01

    Systemic inflammatory mediators, including the protein high-mobility group box 1 (HMGB1), play an important role in the development of acute pancreatitis. Anticoagulants such as danaparoid sodium (DA) may be able to inhibit sepsis-induced inflammation, but the mechanism of action is not well understood. We hypothesized that DA would act as an inhibitor of inflammation and prevent cerulein-induced acute pancreatitis. Male Wistar rats were used as subjects in this study. Each received a bolus of 50 U/kg of DA or saline-injected into the tail vein, followed by 4 injections of 50 mg/kg cerulean (i.p.) at 1-h intervals. Cytokine (IL-6), NO, and HMGB1 levels in serum and pancreatic tissue were measured after the cerulein injection. Pancreas histopathology and wet-dry ratio significantly improved in the DA-injected (50 U/kg) animals compared with saline-injected rats. Serum and pancreatic HMGB1 levels decreased over time in DA-treated animals. Danaparoid sodium also decreased cytokine, NO, and HMGB1 levels during cerulein-induced inflammation. As a result, DA ameliorated pancreas pathology in the rat model of cerulein-induced acute pancreatitis. This study demonstrates that DA treatment prevents cerulein-induced acute pancreatitis in a rat model. This effect may be mediated through inhibition of cytokines, NO, and HMGB1. PMID:18948846

  8. 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

  9. 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.

  10. 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. PMID:23021249

  11. Oral administration of Lactobacillus paracasei alleviates clinical symptoms of colitis induced by dextran sulphate sodium salt in BALB/c mice.

    PubMed

    Pan, T; Guo, H Y; Zhang, H; Liu, A P; Wang, X X; Ren, F Z

    2014-09-01

    The aim of this study was to investigate the alleviating effect of Lactobacillus paracasei subsp. paracasei LC-01 (LC-01) on the murine model of colitis induced by dextran sulphate sodium (DSS). 50 pathogen-free, 6-week-old male BALB/c mice were divided randomly into 5 groups, including a control group and four DSS-LC-01-treated groups (DSS, DSS-106, DSS-108, and DSS-1010 with 0, 1×106, 1×108 and 1×1010 cfu/ml LC-01, respectively). To test the effectiveness of LC-01 as a prophylactic it was administered for 7 days before the onset of the disease in DSS-LC-01-treated mice. After 7 days, colitis was induced by administration of 2.5% (w/v) DSS in drinking water for a further 7 days. The disease activity index (DAI), histological score, myeloperoxidase (MPO) activity and the level of the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumour necrosis factor α (TNF-α) were measured. DAI, histological scores and MPO activity of mice treated with a medium or high dose of LC-01 were significantly lower compared to a low-dose of LC-01 and DSS treatment alone (P<0.05). Colon length shortening could be prevented with increasing dose of LC-01. In addition, the levels of IL-1β and TNF-α were suppressed significantly by treatment with a medium and high dose of LC-01. However, no significant difference in the indices mentioned above were observed between a low dose of LC-01 and treatment with DSS alone (P≯0.05). An appropriate dose of LC-01 can prevent intestinal damage in mice with DSS-induced colitis. The expression of inflammatory cytokines related to pathogenesis of DSS-induced colitis decreased following treatment with LC-01. PMID:24889889

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

    PubMed

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

    2016-04-15

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

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

    PubMed Central

    Wang, Yilin; Wang, Zhengting; Pei, Yaofei; Fan, Rong; Liu, Xiqiang; Wang, Lei; Zhou, Jie; Zheng, Sichang; Zhang, Tianyu; Lin, Yun; Zhang, Maochen; Tao, Ran; Zhong, Jie

    2016-01-01

    It has been established that mammalian target of Rapamycin (mTOR) inhibitors have anti-inflammatory effects in models of experimental colitis. However, the underlying mechanism is largely unknown. In this research, we investigate the anti-inflammatory effects of AZD8055, a potent mTOR inhibitor, on T cell response in dextran sulfate sodium (DSS)-induced colitis in mice, a commonly used animal model of inflammatory bowel diseases (IBD). Severity of colitis is evaluated by changing of body weight, bloody stool, fecal consistency, histology evaluation and cytokine expression. We find that AZD8055 treatment attenuates DSS-induced body weight loss, colon length shortening and pathological damage of the colon. And AZD8055 treatment decreases colonic expression of genes encoding the pro-inflammatory cytokines interferon-γ, interleukin (IL)-17A, IL-1β,IL-6 and tumor necrosis factor(TNF)-a and increases colonic expression of anti-inflammatory cytokines IL-10. We show that AZD8055 treatment decreases the percentages of CD4+ T cells and CD8+ T cells in spleen, lymph nodes and peripheral blood of mice. We also find that AZD8055 treatment significantly reduces the number of T helper 1(TH1) cells and TH17 cells and increases regulatory T (Treg) cells in the lamina propria and mesenteric lymph nodes. Furthermore, we demonstrates that AZD8055 suppresses the proliferation of CD4+ and CD8+ T cells and the differentiation of TH1/TH17 cells and expands Treg cells in vitro. The results suggest that, in experimental colitis, AZD8055 exerts anti-inflammatory effect by regulating T helper cell polarization and proliferation. PMID:27128484

  14. 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.

  15. 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. PMID:25284342

  16. Addition of Berberine to 5-Aminosalicylic Acid for Treatment of Dextran Sulfate Sodium-Induced Chronic Colitis in C57BL/6 Mice.

    PubMed

    Li, Yan-hong; Zhang, Man; Xiao, Hai-tao; Fu, Hai-bo; Ho, Alan; Lin, Cheng-yuan; Huang, Yu; Lin, Ge; Bian, Zhao-xiang

    2015-01-01

    Ulcerative colitis (UC) is a common chronic remitting disease but without satisfactory treatment. Alternative medicine berberine has received massive attention for its potential in UC treatment. Conventional therapies with the addition of berberine are becoming attractive as novel therapies in UC. In the present study, we investigated the preclinical activity of a conventional oral 5-aminosalicylic acid (5-ASA) therapy plus berberine in experimental colitis. A subclinical dose of 5-ASA (200 mg/kg/day) alone or 5-ASA plus berberine (20 mg/kg/day) was orally administered for 30 days to C57BL/6 mice with colitis induced by three cycles of 2% dextran sulfate sodium (DSS). The disease severity, inflammatory responses, drug accumulation and potential toxicity of colitis mice were examined. The results showed that comparing to 5-ASA alone, 5-ASA plus berberine more potently ameliorated DSS-induced disease severity, colon shortening, and colon histological injury. Further, the up-regulation in mRNA level of colonic TNF-α as well as NFκB and JAK2 phosphorylation caused by DSS were more pronouncedly reversed in animals treated with the combination therapy than those treated with 5-ASA alone. Moreover, the addition of berberine to 5-ASA more significantly inhibited lymphocyte TNF-α secretion of DSS mice than 5-ASA alone. In the meanwhile, no extra drug accumulation or potential toxicity to major organs of colitis mice was observed with this combination treatment. In summary, our studies provide preclinical rationale for the addition of berberine to 5-ASA as a promising therapeutic strategy in clinic by reducing dose of standard therapy.

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

    PubMed

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

    2003-07-01

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

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

    PubMed

    Hu, Shurong; Chen, Mengmeng; Wang, Yilin; Wang, Zhengting; Pei, Yaofei; Fan, Rong; Liu, Xiqiang; Wang, Lei; Zhou, Jie; Zheng, Sichang; Zhang, Tianyu; Lin, Yun; Zhang, Maochen; Tao, Ran; Zhong, Jie

    2016-01-01

    It has been established that mammalian target of Rapamycin (mTOR) inhibitors have anti-inflammatory effects in models of experimental colitis. However, the underlying mechanism is largely unknown. In this research, we investigate the anti-inflammatory effects of AZD8055, a potent mTOR inhibitor, on T cell response in dextran sulfate sodium (DSS)-induced colitis in mice, a commonly used animal model of inflammatory bowel diseases (IBD). Severity of colitis is evaluated by changing of body weight, bloody stool, fecal consistency, histology evaluation and cytokine expression. We find that AZD8055 treatment attenuates DSS-induced body weight loss, colon length shortening and pathological damage of the colon. And AZD8055 treatment decreases colonic expression of genes encoding the pro-inflammatory cytokines interferon-γ, interleukin (IL)-17A, IL-1β,IL-6 and tumor necrosis factor(TNF)-a and increases colonic expression of anti-inflammatory cytokines IL-10. We show that AZD8055 treatment decreases the percentages of CD4+ T cells and CD8+ T cells in spleen, lymph nodes and peripheral blood of mice. We also find that AZD8055 treatment significantly reduces the number of T helper 1(TH1) cells and TH17 cells and increases regulatory T (Treg) cells in the lamina propria and mesenteric lymph nodes. Furthermore, we demonstrates that AZD8055 suppresses the proliferation of CD4+ and CD8+ T cells and the differentiation of TH1/TH17 cells and expands Treg cells in vitro. The results suggest that, in experimental colitis, AZD8055 exerts anti-inflammatory effect by regulating T helper cell polarization and proliferation. PMID:27128484

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

    PubMed

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

    2016-04-15

    Oroxyloside, as a metabolite of oroxylin A, may harbor various beneficial bioactivities which have rarely been reported in the previous studies. Here we established the dextran sulfate sodium (DSS)-induced experimental colitis and evaluated the anti-inflammatory effect of oroxyloside in vivo. As a result, oroxyloside attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. Furthermore, oroxyloside inhibited inflammatory cell infiltration and decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities as well. The production of pro-inflammatory cytokines in serum and colon was also significantly reduced by oroxyloside. We unraveled the underlying mechanisms that oroxyloside inhibited NF-κB pathway by activating Peroxisome Proliferator-Activated Receptor γ (PPARγ) to attenuate DSS-induced colitis. Moreover, we investigated the anti-inflammatory effect and mechanisms of oroxyloside in the mouse macrophage cell line RAW264.7 and bone marrow derived macrophages (BMDM). Oroxyloside decreased several LPS-induced inflammatory cytokines, including IL-1β, IL-6 and TNF-α in RAW264.7 and BMDM. We also found that oroxyloside inhibited LPS-induced activation of NF-κB signaling pathway via activating PPARγ in RAW 264.7 and BMDM. Docking study showed that oroxyloside could bind with PPARγ. GW9662, the inhibitor of PPARγ, and PPARγ siRNA transfection blocked the effect of oroxyloside on PPARγ activation. Our study suggested that oroxyloside prevented DSS-induced colitis by inhibiting NF-κB pathway through PPARγ activation. Therefore, oroxyloside may be a promising and effective agent for inflammatory bowel disease (IBD). PMID:26947454

  20. 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

  1. Baicalin down regulates the expression of TLR4 and NFkB-p65 in colon tissue in mice with colitis induced by dextran sulfate sodium

    PubMed Central

    Feng, Jinshan; Guo, Cancan; Zhu, Yuzhen; Pang, Liping; Yang, Zheng; Zou, Ying; Zheng, Xuebao

    2014-01-01

    Background: Baicalin is one of flavonoid extracts from Scutellaria baicalensis, which has several functions including anti-inflammation, anti-bacteria, antitumor and et al. However, the mechanisms of anti-inflammatory of baicalin in ulcerative colitis is not clear. Methods: Mice colitis models were established by dextran sodium sulfate, Mice administrated with baicalin (100 mg/kg) and mesalazine (100 mg/kg) twice daily by intragastric injection for 7 days after colitis induced were defined as treated group. Then the mice were sacrificed and the colon samples were collected. Toll-like receptor-2, 4, 9 were detected by immunohistochemistry. Signaling proteins such as TLR4, MyD88, and NF-κB p65 were analyzed by western blotting. Cytokine’s mRNA include TNF-α, IL-6 IL-10 and IL-13 were measured by reverse transcription polymerase chain reaction. Modified disease activity index were used to analyse the severity of the disease by assessed of diarrhea, stool (occult) blood and body weight loss of the mice. Results: Compared with control and model groups, modified disease activity index in baicalin and mesalazine treated, mice decreased gradually. Immunohistochemistry analysis showed the expression of TLR4, but not TLR2 and TLR9, in the mucosa of mice colon were decreased. Western blot analysis showed that in colitis model, the expression of NF-κB p65 and TLR4 decreased (P < 0.05), while the expression of MyD88 increased significantly compared to control group, and MyD88 expression can not be repressed by baicalin (P < 0.05). Baicalin and mesalazine treatment suppressed the expression of TNF-α, IL-6 and IL-13 mRNA (P < 0.05), yet up-regulated the expression of IL-10 mRNA (P < 0.05), compared to the DDS and control groups. Conclusions: Baicalin administration by intragastric injection ameliorates the severity of colon inflammation. The possible mechanism of anti-inflammatory response by baicalin may involve in the blocking of the TLR4/NF-κB-p65/IL-6 signaling pathway

  2. Effects of natural raw meal (NRM) on high-fat diet and dextran sulfate sodium (DSS)-induced ulcerative colitis in C57BL/6J mice

    PubMed Central

    Shin, Sung-Ho; Song, Jia-Le; Park, Myoung-Gyu; Park, Mi-Hyun; Hwang, Sung-Joo

    2015-01-01

    BACKGROUND/OBJECTIVES Colitis is a serious health problem, and chronic obesity is associated with the progression of colitis. The aim of this study was to determine the effects of natural raw meal (NRM) on high-fat diet (HFD, 45%) and dextran sulfate sodium (DSS, 2% w/v)-induced colitis in C57BL/6J mice. MATERIALS/METHODS Body weight, colon length, and colon weight-to-length ratio, were measured directly. Serum levels of obesity-related biomarkers, triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), insulin, leptin, and adiponectin were determined using commercial kits. Serum levels of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were detected using a commercial ELISA kit. Histological study was performed using a hematoxylin and eosin (H&E) staining assay. Colonic mRNA expressions of TNF-α, IL-1β, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were determined by RT-PCR assay. RESULTS Body weight and obesity-related biomarkers (TG, TC, LDL, HDL, insulin, leptin, and adiponectin) were regulated and obesity was prevented in NRM treated mice. NRM significantly suppressed colon shortening and reduced colon weight-to-length ratio in HFD+DSS induced colitis in C57BL/6J mice (P < 0.05). Histological observations suggested that NRM reduced edema, mucosal damage, and the loss of crypts induced by HFD and DSS. In addition, NRM decreased the serum levels of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6 and inhibited the mRNA expressions of these cytokines, and iNOS and COX-2 in colon mucosa (P < 0.05). CONCLUSION The results suggest that NRM has an anti-inflammatory effect against HFD and DSS-induced colitis in mice, and that these effects are due to the amelioration of HFD and/or DSS-induced inflammatory reactions. PMID:26634051

  3. 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.

  4. [A case of portal vein thrombosis complicating acute cholangitis treated successfully with danaparoid sodium].

    PubMed

    Oku, Takatomi; Kubo, Yasunori; Miseki, Tetsuya; Sakai, Takashi; Yamakawa, Atsushi; Sugata, Hideaki

    2010-11-01

    An 81-year-old woman was referred to our hospital with a diagnosis of acute cholangitis. Endoscopic retrograde cholangiography revealed a common bile duct (CBD) stone. In addition, CT showed thrombus of the right portal vein. Endoscopic sphincterotomy was performed to remove the CBD stone. Thrombosis was treated successfully with danaparoid sodium. It was speculated that the treatment of the acute cholangitis induced thrombolysis by the auto-fibrinolysis system and danaparoid sodium prevented the development of thrombus formation in this case. PMID:21071899

  5. 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

  6. Effects of diclofenac sodium and octreotide on treatment of caerulein-induced acute pancreatitis in mice

    PubMed Central

    Ozer Cakir, Ozlem; Esen, Hasan; Toker, Aysun; Ataseven, Huseyin; Demir, Ali; Polat, Hakki

    2015-01-01

    Background: Research continues to develop novel therapeutic modalities that particularly focus on the pathogenesis of acute pancreatitis. This study aimed to assess the effects of diclofenac sodium and octreotide, alone or in combination, on pancreatic enzymes, pancreatic myeloperoxidase activity, histopathology and apoptosis of pancreas cells, using a model of experimentally induced acute pancreatitis. Objectives: We aimed to demonstrate effects of diclofenac sodium, octreotide and their combined use on pancreatic enzymes, activity of pancreatic myeloperoxidase (MPO) activity, histopathology and apoptosis of pancreas on treatment of caerulin-induced experimental acute pancreatitis. Materials and methods: Caerulin-induced acute pancreatitis model was created using a total of 58 male BALB-C mice of 25 gr in seven groups. Serum amylase, lipase levels and pancreatic myeloperoxidase activity were examined as well as apoptotic values in pancreatic acinar cells through TUNNEL method. Histopathology of pancreas was evaluated for presence of edema, hemorrhage, parenchymal necrosis, fat necrosis, leukocyte infiltration, and fibrosis. Results: In the diclofenac sodium group, apoptotic values in the pancreatic acinar cells were found to be statistically lower than in the acute pancreatitis group in terms of parenchymal necrosis and hemorrhage scores (P = 0.007, P = 0.002, and P = 0.052, respectively). No statistically significant differences were found in serum level of amylase, lipase, pancreatic myeloperoxidase activity and the other histopathological scores (P > 0.05). Conclusion: Diclofenac sodium, a cost-effective agent with a favorable side-effect profile, may represent a novel therapeutic agent for the treatment of acute pancreatitis. Findings of this study suggest a better efficacy for diclofenac sodium monotherapy as compared to octreotide alone or octreotide/diclofenac combination. PMID:26770346

  7. Glycoprotein isolated from Styrax japonica Siebold et al. Zuccarini inhibits oxidative and pro-inflammatory responses in HCT116 colonic epithelial cells and dextran sulfate sodium-treated ICR mice.

    PubMed

    Lee, Sei-Jung; Lee, Jin; Song, Sooyeon; Lim, Kye-Taek

    2016-01-01

    This study was carried out to investigate the anti-inflammatory potentials of a 38 kDa glycoprotein isolated from Styrax japonica Siebold et al Zuccarini (SJSZ glycoprotein). We found that SJSZ glycoprotein has concentration-dependent scavenging activity against DPPH and hydroxyl radicals in the cell-free systems. In colonic epithelial cells (HCT116 cells), the results showed that SJSZ glycoprotein inhibits the production of reactive oxygen species (ROS) induced by glucose/glucose oxidase (G/GO) in a concentration-dependent manner. Experimental mouse colitis was induced by adding dextran sulfate sodium (DSS) to the drinking water at a concentration of 4% (w/v) for 7 days. We figured out that administration of SJSZ glycoprotein (10 mg/kg) lowers the levels of disease activity index, myeloperoxidase activity, and histological inflammation in DSS-treated mice. In addition, SJSZ glycoprotein inhibited plasmic thiobarbituric acid reactive substances (TBARS) formation, nitric oxide (NO) production, and lactate dehydrogenase (LDH) release, accompanying the inhibition of colonic inflammatory signal proteins (NF-κB, iNOS, and COX-2) and inflammation-related cytokines (IL-1β, IL-6, and TNF-α). These results indicate that SJSZ glycoprotein inhibits oxidative and pro-inflammatory responses in mouse colitis. PMID:26631293

  8. Glycoprotein isolated from Styrax japonica Siebold et al. Zuccarini inhibits oxidative and pro-inflammatory responses in HCT116 colonic epithelial cells and dextran sulfate sodium-treated ICR mice.

    PubMed

    Lee, Sei-Jung; Lee, Jin; Song, Sooyeon; Lim, Kye-Taek

    2016-01-01

    This study was carried out to investigate the anti-inflammatory potentials of a 38 kDa glycoprotein isolated from Styrax japonica Siebold et al Zuccarini (SJSZ glycoprotein). We found that SJSZ glycoprotein has concentration-dependent scavenging activity against DPPH and hydroxyl radicals in the cell-free systems. In colonic epithelial cells (HCT116 cells), the results showed that SJSZ glycoprotein inhibits the production of reactive oxygen species (ROS) induced by glucose/glucose oxidase (G/GO) in a concentration-dependent manner. Experimental mouse colitis was induced by adding dextran sulfate sodium (DSS) to the drinking water at a concentration of 4% (w/v) for 7 days. We figured out that administration of SJSZ glycoprotein (10 mg/kg) lowers the levels of disease activity index, myeloperoxidase activity, and histological inflammation in DSS-treated mice. In addition, SJSZ glycoprotein inhibited plasmic thiobarbituric acid reactive substances (TBARS) formation, nitric oxide (NO) production, and lactate dehydrogenase (LDH) release, accompanying the inhibition of colonic inflammatory signal proteins (NF-κB, iNOS, and COX-2) and inflammation-related cytokines (IL-1β, IL-6, and TNF-α). These results indicate that SJSZ glycoprotein inhibits oxidative and pro-inflammatory responses in mouse colitis.

  9. Downregulation of CYP3A and P-glycoprotein in the secondary inflammatory response of mice with dextran sulfate sodium-induced colitis and its contribution to cyclosporine A blood concentrations.

    PubMed

    Kawauchi, Shoji; Nakamura, Tsutomu; Miki, Ikuya; Inoue, Jun; Hamaguchi, Tsuneo; Tanahashi, Toshihito; Mizuno, Shigeto

    2014-01-01

    CYP3A and P-glycoprotein (P-gp) play important roles in drug metabolism and excretion; however, their functions in pathological conditions remain unclear. Hepatobiliary abnormalities have been described in patients with ulcerative colitis, which may affect drug metabolism and excretion in the liver and small intestine. We examined the functions of CYP3A and P-gp in the liver and small intestine of mice with dextran sodium sulfate (DSS)-induced colitis. Up to day 7, inflammatory markers were significantly increased in the livers of DSS-treated mice, accompanied by decreased CYP3A. Additionally hepatobiliary transporters and Pregnane X receptor, which regulates the transcriptional activation of CYP3A, were reduced. Both CYP3A and P-gp were significantly decreased in the upper small intestine of DSS-treated mice on day 7. This was associated with the increased expression of inducible nitric oxide synthase, but not changes in nuclear receptor expression. On day 7 of DSS treatment, the concentrations of cyclosporine A (CsA), a substrate of both CYP3A and P-gp, were significantly higher than controls. These results indicated the existence of a second inflammatory response in the liver and upper small intestine of mice with DSS-induced colitis, and bioavailability of CsA was increased by the dysfunction of CYP3A and P-gp in these organs.

  10. 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.

  11. Acute cyanide intoxication treated with a combination of hydroxycobalamin, sodium nitrite, and sodium thiosulfate.

    PubMed

    Mannaioni, Guido; Vannacci, Alfredo; Marzocca, Cosimo; Zorn, Anna Monica; Peruzzi, Sandro; Moroni, Flavio

    2002-01-01

    An 80-year-old diabetic patient was admitted to the hospital because of sudden unconsciousness and severe metabolic acidosis. His son reported the possibility of cyanide poisoning. Clinical data and the detection of cyanide in blood and gastric material confirmed this possibility. Supportive therapy and the following antidotes--sodium nitrite two doses 300 mg i.v., sodium thiosulfate 3 g i.v., and hydroxocobalamin 4 g in 24 hours--were administered immediately and the patient completely recovered in 48 hours. Our observations suggest that timely and appropriate use of antidotes for cyanide intoxication may prevent death, even in aged diabetic patients. PMID:12126191

  12. Sodium MRI in Multiple Sclerosis is Compatible with Intracellular Sodium Accumulation and Inflammation-Induced Hyper-Cellularity of Acute Brain Lesions

    PubMed Central

    Biller, Armin; Pflugmann, Isabella; Badde, Stephanie; Diem, Ricarda; Wildemann, Brigitte; Nagel, Armin M.; Jordan, J.; Benkhedah, Nadia; Kleesiek, Jens

    2016-01-01

    The cascade of inflammatory pathogenetic mechanisms in multiple sclerosis (MS) has no specific conventional MRI correlates. Clinicians therefore stipulate improved imaging specificity to define the pathological substrates of MS in vivo including mapping of intracellular sodium accumulation. Based upon preclinical findings and results of previous sodium MRI studies in MS patients we hypothesized that the fluid-attenuated sodium signal differs between acute and chronic lesions. We acquired brain sodium and proton MRI data of N = 29 MS patients; lesion type was defined by the presence or absence of contrast enhancement. N = 302 MS brain lesions were detected, and generalized linear mixed models were applied to predict lesion type based on sodium signals; thereby controlling for varying numbers of lesions among patients and confounding variables such as age and medication. Hierarchical model comparisons revealed that both sodium signals average tissue (χ2(1) = 27.89, p < 0.001) and fluid-attenuated (χ2(1) = 5.76, p = 0.016) improved lesion type classification. Sodium MRI signals were significantly elevated in acute compared to chronic lesions compatible with intracellular sodium accumulation in acute MS lesions. If confirmed in further studies, sodium MRI could serve as biomarker for diagnostic assessment of MS, and as readout parameter in clinical trials promoting attenuation of chronic inflammation. PMID:27507776

  13. Sodium MRI in Multiple Sclerosis is Compatible with Intracellular Sodium Accumulation and Inflammation-Induced Hyper-Cellularity of Acute Brain Lesions.

    PubMed

    Biller, Armin; Pflugmann, Isabella; Badde, Stephanie; Diem, Ricarda; Wildemann, Brigitte; Nagel, Armin M; Jordan, J; Benkhedah, Nadia; Kleesiek, Jens

    2016-01-01

    The cascade of inflammatory pathogenetic mechanisms in multiple sclerosis (MS) has no specific conventional MRI correlates. Clinicians therefore stipulate improved imaging specificity to define the pathological substrates of MS in vivo including mapping of intracellular sodium accumulation. Based upon preclinical findings and results of previous sodium MRI studies in MS patients we hypothesized that the fluid-attenuated sodium signal differs between acute and chronic lesions. We acquired brain sodium and proton MRI data of N = 29 MS patients; lesion type was defined by the presence or absence of contrast enhancement. N = 302 MS brain lesions were detected, and generalized linear mixed models were applied to predict lesion type based on sodium signals; thereby controlling for varying numbers of lesions among patients and confounding variables such as age and medication. Hierarchical model comparisons revealed that both sodium signals average tissue (χ(2)(1) = 27.89, p < 0.001) and fluid-attenuated (χ(2)(1) = 5.76, p = 0.016) improved lesion type classification. Sodium MRI signals were significantly elevated in acute compared to chronic lesions compatible with intracellular sodium accumulation in acute MS lesions. If confirmed in further studies, sodium MRI could serve as biomarker for diagnostic assessment of MS, and as readout parameter in clinical trials promoting attenuation of chronic inflammation. PMID:27507776

  14. [Effects of Faecalibacterium prausnitzii supernatant on Th17 cell and IL-17A in dextran sulfate sodium-induced ulcerative colitis mice].

    PubMed

    Huang, Xiaoli; Zhang, Xin; Fei, Xianyan; Chen, Zhaogui; Yu, Chengong

    2015-12-01

    目的:探讨普拉梭菌(Faecalibacterium prausnitzii,Fp)上清对葡聚糖酸钠(dextran sulfate sodium,DSS)诱导的小鼠溃疡性结肠炎的预防和治疗作用及机制。方法:40只雄性C57BL/6J小鼠随机分为对照组、模型组、治疗组、预防组,每组10只。观察各组小鼠的结肠组织病理学评分,计算脾Th17细胞占单核细胞比例;检测外周血浆白细胞介素-17A(interleukin-17A,IL-17A)和IL-6水平,以及结肠黏膜组织转录因子维甲酸相关孤儿核受体-γt(transcription factor retinoic acid-related orphan receptor-γt,ROR-γt),IL-17A和IL-6的mRNA表达情况。结果:治疗组和预防组小鼠结肠组织病理损伤较模型组轻,其病理组织学评分较模型组均明显下降(均P<0.05),预防组和治疗组之间差异无统计学意义(P>0.05);治疗组和预防组脾辅助性T细胞(helper T cell,Th17)比例较模型组均明显下降(均P<0.01);治疗组血浆IL-17A和IL-6水平也较模型组均明显降低(均P<0.05),结肠组织ROR-γt,IL-17A和IL-6的mRNA表达均明显低于模型组(均P<0.05),但预防组血浆IL-6水平和结肠组织IL-6 mRNA表达与模型组差异无明显统计学意义(均P>0.05)。结论:Fp上清可预防和治疗DSS所致的小鼠结肠炎,其机制可能为抑制脾和肠道Th17细胞的生成,减少外周血和结肠组织炎性细胞因子IL-17A分泌;Fp上清可通过降低IL-6水平来治疗结肠炎。.

  15. Iron Dextran Injection

    MedlinePlus

    ... called iron replacement products. It works by replenishing iron stores so that the body can make more red blood cells. ... and order certain lab tests to check your body's response to iron dextran injection.Before having any laboratory test, tell ...

  16. Soy protein diet, but not Lactobacillus rhamnosus GG, decreases mucin-1, trefoil factor-3, and tumor necrosis factor-α in colon of dextran sodium sulfate-treated C57BL/6 mice.

    PubMed

    Jiang, Huanyi; Przybyszewski, Joseph; Mitra, Debjani; Becker, Chad; Brehm-Stecher, Byron; Tentinger, Amy; MacDonald, Ruth S

    2011-07-01

    The incidence of inflammatory bowel diseases has increased during recent decades. Within the colon, the families of mucins (MUC) and trefoil factors (TFF) facilitate mucosal protection. Probiotic administration influences the intestinal MUC layer. Additionally, food components may affect gut microflora or have direct effects on the MUC barrier. Our objective was to determine whether diet and/or Lactobacillus rhamnosus GG (LGG) would mediate dextran sodium sulfate (DSS)-induced colitis by altering expression of the MUC and TFF genes. C57BL/6 mice were fed diets containing 20% (wt:wt) casein, soy, or whey proteins with or without LGG for 12 d. Seven days after starting LGG diets, the mice were given 2% DSS in drinking water for 4 d. Two additional casein groups with or without LGG were given tap water, for a total of 8 groups. One day after the DSS treatment, the mice were killed and the colon and cecum tissues and cecum contents were collected and analyzed by qRT-PCR. Whey protein significantly increased cecal LGG content compared with the other diets. In the casein diet groups, MUC1 and TFF-3 expression in colon was significantly induced by DSS independent of LGG. Compared with other DSS-treated groups, soy protein decreased MUC-1 and TFF-3 in the colon. Similarly, soy protein decreased the impact of DSS on inflammatory scores, TNFα gene expression, and colon shortening. There was no overall effect of LGG on these measurements. In conclusion, soy protein suppressed the DSS-induced inflammatory stimulation of MUC, TFF, and TNFα gene expression independently of LGG.

  17. Rapid induction of colon carcinogenesis in CYP1A-humanized mice by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate.

    PubMed

    Cheung, Connie; Loy, Shea; Li, Guang Xun; Liu, Anna B; Yang, Chung S

    2011-02-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant heterocyclic amine produced during the cooking of meats and fish, is suspected to be a human carcinogen. Metabolic activation of PhIP is primarily mediated by the enzyme cytochrome P450 (CYP) 1A2. Metabolism of PhIP by CYP1A2 differs considerably between humans and rodents, with more N(2)-hydroxylation (activation) and less 4'-hydroxylation (detoxication) in humans. Transgenic CYP1A-humanized mice (hCYP1A-mice), which have the human CYP1A1 and CYP1A2 genes but lack the murine orthologs Cyp1a1 and Cyp1a2, provide an excellent opportunity to develop a relevant model to study dietary-induced colon carcinogenesis. The treatment with 200 mg/kg PhIP by oral gavage, followed by 1.5% dextran sodium sulfate (DSS) in the drinking water for 7 days, was found to be an effective combination to induce colon carcinogenesis in hCYP1A-mice. Tumor multiplicity at week 6 was calculated to be 3.75 ± 0.70 and for week 10 was 3.90 ± 0.61 with 80-95% of the tumors being adenocarcinomas. No tumors were found in the similarly treated wild-type mice. Western blots revealed overexpression of β-catenin, c-Myc, cyclin D1, inducible nitric oxide synthase and cyclooxygenase-2 in colon tumor samples. Strong nuclear localization of β-catenin was observed in tumors. These results illustrate that PhIP and DSS combination produces rapid colon carcinogenesis in hCYP1A-mice and this is an effective model to mimic human colon carcinogenesis.

  18. The epigenetic effects of aspirin: the modification of histone H3 lysine 27 acetylation in the prevention of colon carcinogenesis in azoxymethane- and dextran sulfate sodium-treated CF-1 mice.

    PubMed

    Guo, Yue; Liu, Yue; Zhang, Chengyue; Su, Zheng-Yuan; Li, Wenji; Huang, Mou-Tuan; Kong, Ah-Ng

    2016-06-01

    Colorectal cancer (CRC) is the third most common cancer worldwide. Chronic inflammation appears to enhance the risk of CRC. Emerging evidence has suggested that epigenetic mechanisms play an important role in CRC. Aspirin [acetylsalicylic acid (ASA)] has been shown to prevent CRC; however, the epigenetic mechanisms of its action remain unknown. This study investigated the protective role of ASA in azoxymethane (AOM)-initiated and dextran sulfate sodium (DSS)-promoted colitis-associated colon cancer (CAC) and examined the epigenetic effects, particularly on histone 3 lysine 27 acetylation (H3K27ac), underlying the preventive effect of ASA. CF-1 mice were fed with AIN-93M diet with or without 0.02% ASA from 1 week prior to AOM initiation until the mice were killed 20 weeks after AOM injection. Our results showed that AOM/DSS + ASA significantly suppressed inflammatory colitis symptoms and tumor multiplicity. AOM/DSS + ASA reduced AOM/DSS-induced protein expression and the activity of histone deacetylases (HDACs) and globally restored H3K27ac. Furthermore, AOM/DSS + ASA inhibited AOM/DSS-induced enrichment of H3K27ac in the promoters of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) that corresponded to the dramatic suppression of the messenger RNA (mRNA) and protein levels. Surprisingly, no significant changes in the H3K27ac abundance in the prostaglandin-endoperoxide synthase 2 (Cox-2) promoters or in the Cox-2 mRNA and protein expression were observed. Collectively, our results suggest that a potential novel epigenetic mechanism underlies the chemopreventive effects of ASA, and this mechanism attenuates CAC in AOM/DSS-induced CF-1 mice via the inhibition of HDACs and the modification of H3K27ac marks that suppress iNOS, TNF-α and IL-6. PMID:27207670

  19. 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

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

    PubMed

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

    2016-08-15

    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(fh318). After treatment with 1mM sodium arsenite, the survival of nrf2a(fh318) larvae was significantly shorter 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.

  1. 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. PMID:26752182

  2. Sodium

    MedlinePlus

    ... sodium. Doctors recommend you eat less than 2.4 grams per day. That equals about 1 teaspoon of table salt a day. Reading food labels can help you see how much sodium is in prepared foods. NIH: National Heart, Lung, and Blood Institute

  3. [Electron probe microanalysis of potassium, sodium, and chlorine levels in the cardiomyocyte cytoplasm during acute ischemia].

    PubMed

    Pogorelov, A G; Pogorelova, V N; Pogorelova, M A

    2010-01-01

    Electron probe microanalysis was applied to determine cytoplasmic elemental (K, Na, Cl) concentrations in cardiac cells of the rat (Wistar). Potassium, sodium and chlorine contents were measured in papillary muscle myocytes of the rat heart perfused by the Langendorff's procedure. Ischemic depletion was created by perfusion with deeply deoxygenated Tirode's solution in the absence of glucose. It was found that the initial phase of acute ischemia is characterized by the potassium deficiency and the accumulation of sodium and chlorine in cardiac myocytes. It should be noted that changes in the total charge of the main intracellular cations (K+, Na+) do not compensate for the increased chlorine concentration. This result can be accounted for by the appearance of ionic (K+ and Cl-) transport coupled with the removal of lactate anions produced in cardiomyocytes during anaerobic glycolysis. PMID:21033355

  4. Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis

    PubMed Central

    Wu, Xian-lin; Li, Jie-xing; Li, Zhen-dong; Liu, Da-sheng; Lu, Su-hong; Liu, Kang-li; Duan, Hong-yan; Luo, Yu-hong

    2015-01-01

    Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance. PMID:26557854

  5. Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis.

    PubMed

    Wu, Xian-Lin; Li, Jie-Xing; Li, Zhen-Dong; Liu, Da-Sheng; Lu, Su-Hong; Liu, Kang-Li; Duan, Hong-Yan; Luo, Yu-Hong

    2015-01-01

    Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance. PMID:26557854

  6. The effect of sodium tetraborate and alum in the management of acute childhood diarrhoea.

    PubMed

    Aung, M M; U, P P

    1986-03-01

    The effect of oral rehydration (OR) has been well established in the management of dehydration in acute childhood diarrhoea. Many authors have been trying to find additives of all types which would be effective in retaining oral fluids and promoting their active absorption into the circulation. Any agent which will effectively reduce oral rehydration requirements should be considered for prospective studies. Amongst the traditional medicines, it was noticed that sodium tetraborate (borax) and alum reduced appreciably the fluid requirement in many cases of acute childhood diarrhoea. This traditional usage of these chemicals without any noticeable side effects has been described for centuries. During preliminary observations on 26 of our children given these salts no side effects were detected.

  7. Induction of angiogenesis via topical delivery of basic-fibroblast growth factor from polyvinyl alcohol-dextran blend hydrogel in an ovine model of acute myocardial infarction.

    PubMed

    Fathi, Ezzatollah; Nassiri, Seyed Mahdi; Atyabi, Nahid; Ahmadi, Seyed Hossein; Imani, Mohammad; Farahzadi, Raheleh; Rabbani, Shahram; Akhlaghpour, Shahram; Sahebjam, Mohammad; Taheri, Mohammad

    2013-09-01

    Hydrogels are currently used as interesting constructs for the delivery of proteins. In this study, a novel polyvinyl alcohol-dextran (PVA-Dex) blend hydrogel was used for controlled delivery of basic-fibroblast growth factor (bFGF). These biocompatible constructs were sutured to the epicardium as patches on the heart surface to provide slow release of bFGF to the infarcted site in an ovine model of myocardial infarction (MI). Eighteen sheep were randomly divided into three groups (n = 6 each), including group I (control without any patch and bFGF), group II (patch without bFGF) and group III (patch incorporating 100 µg bFGF). They were subjected to coronary artery ligation after lateral thoracotomy, and then in groups II and III the patches were implanted 20-30 min after MI. Cardiac function was assessed by both echocardiography and magnetic resonance imaging (MRI) 2 months after implantation. Then the animals were sacrificed and the hearts subjected to histopathological examination, immunohistochemistry and electron microscopy. Heart lysates were subject to protein expression analysis through western blotting. The results showed that sustained release of bFGF using PVA-Dex blend hydrogel strongly stimulated angiogenesis and increased wall thickness index in the infarcted myocardium. The patch also significantly attenuated the increase in left ventricular end-systolic diameter, but it did not improve cardiac function within 2 months of myocardial infarction. In conclusion, PVA-Dex gel incorporating bFGF can be used as a sustained release construct for therapeutic angiogenesis in ischaemic heart disease.

  8. Rheological Study of Dextran-Modified Magnetite Nanoparticle Water Suspension

    NASA Astrophysics Data System (ADS)

    Józefczak, A.; Hornowski, T.; Rozynek, Z.; Skumiel, A.; Fossum, J. O.

    2013-04-01

    The aim of this work is to investigate the effect of surface modification of superparamagnetic magnetite nanoparticles (sterically stabilized by sodium oleate) by the dextran biocompatible layer on the rheological behavior of water-based magnetic fluids. The flow curves were measured as a function of the magnetic field strength by means of rheometry. The measured viscosity is generally dependent on both the particle concentration and the geometrical factors such as the particle shape and thickness of the adsorbed layers. The rheological properties of the magnetic fluids studied show the effect of the magnetic field strength and the presence of the surfactant second layer (dextran) on their viscosity.

  9. Early use of inhaled nedocromil sodium in children following an acute episode of asthma

    PubMed Central

    Edwards, A; Lyons, J; Weinberg, E; Weinberg, F; Gillies, J; Reid, G; Robertson, C; Robinson, P; Dalton, M; Van Asperen, P; Wilson, C; Mullineux, J; Mullineux, A; Sly, P; Cox, M; Isles, A

    1999-01-01

    BACKGROUND—Current guidelines on the treatment of childhood asthma recommend the introduction of an anti-inflammatory drug in children who have persistent symptoms and require regular treatment with a bronchodilator. The efficacy and safety of inhaled nedocromil sodium (Tilade Mint aerosol) administered using a Fisonair spacer at a dose of 4 mg three times daily was compared with placebo in the treatment of asthmatic children aged 6-12 years who are symptomatic and recovering from an acute exacerbation of asthma.
METHODS—A group comparative, double blind, placebo controlled trial was performed in children who were recovering from an acute episode of asthma following treatment in the emergency department of the hospital or in children referred from their general practitioner following a wheezing episode and documented evidence of at least two previous episodes of wheezing. A two week baseline period on existing bronchodilator treatment was followed by a 12 week treatment period on either nedocromil sodium (2 mg/puff) or placebo. Both treatments were administered using a Fisonair spacer at a dose of two puffs three times daily. Changes from baseline values in daytime asthma and night time asthma symptom scores, usage of rescue bronchodilators, mean peak expiratory flow (PEF) recorded twice daily on diary cards, patients' opinion of treatment, and withdrawals due to treatment failure were measured during the primary treatment period (last six weeks of treatment).
RESULTS—One hundred and forty two children aged 6-12 years entered the baseline period. Sixty three were withdrawn due to failure to meet the entry criteria (18) or the criteria for asthma symptom severity (15) or reversibility (9), because they developed uncontrolled asthma (2), because they took disallowed treatment (2), or for other non-trial related reasons (17). Seventy nine patients (46boys) of mean age 8.8 years entered the treatment period. There were significant differences in the changes

  10. 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.

  11. 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.

    2015-01-01

    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.

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

    PubMed

    Wang, Ning; Dorman, Rebecca A; Ingersoll, Christopher G; Hardesty, Doug 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 1 mg K/L to 3 mg 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.

  13. 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

  14. Rosmarinic Acid Attenuates Sodium Taurocholate-Induced Acute Pancreatitis in Rats by Inhibiting Nuclear Factor-κB Activation.

    PubMed

    Fan, Yu-Ting; Yin, Guo-Jian; Xiao, Wen-Qin; Qiu, Lei; Yu, Ge; Hu, Yan-Ling; Xing, Miao; Wu, De-Qing; Cang, Xiao-Feng; Wan, Rong; Wang, Xing-Peng; Hu, Guo-Yong

    2015-01-01

    Rosmarinic Acid (RA), a caffeic acid ester, has been shown to exert anti-inflammation, anti-oxidant and antiallergic effects. Our study aimed to investigate the effect of RA in sodium taurocholate ( NaTC )-induced acute pancreatitis, both in vivo and in vitro. In vivo, RA (50 mg/kg) was administered intraperitoneally 2 h before sodium taurocholate injection. Rats were sacrificed 12 h, 24 h or 48 h after sodium taurocholate injection. Pretreatment with RA significantly ameliorated pancreas histopathological changes, decreased amylase and lipase activities in serum, lowered myeloperoxidase activity in the pancreas, reduced systematic and pancreatic interleukin-1 β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) levels, and inhibited NF-κB translocation in pancreas. In vitro, pretreating the fresh rat pancreatic acinar cells with 80 μ mol/L RA 2 h before 3750 nmol/L sodium taurocholate or 10 ng/L TNF-α administration significantly attenuated the reduction of isolated pancreatic acinar cell viability and inhibited the nuclear activation and translocation of NF-κB. Based on our findings, RA appears to attenuate damage in sodium taurocholate-induced acute pancreatitis and reduce the release of inflammatory cytokines by inhibiting the activation of NF-κB. These findings might provide a basis for investigating the therapeutic role of RA in managing acute pancreatits. PMID:26364660

  15. Acute Self-Induced Poisoning With Sodium Ferrocyanide and Methanol Treated With Plasmapheresis and Continuous Renal Replacement Therapy Successfully

    PubMed Central

    Liu, Zhenning; Sun, Mingli; Zhao, Hongyu; Zhao, Min

    2015-01-01

    Abstract Self-induced poisoning with chemicals is one of the most commonly used suicide methods. Suicide attempts using massive pure sodium ferrocyanide and methanol are rare. This article discusses the management of acute intentional self-poisoning using sodium ferrocyanide and methanol. We present a case of acute self-induced poisoning using sodium ferrocyanide and methanol admitted to our hospital 2 hours after ingestion. He was deeply unconscious and unresponsive to painful stimuli. The laboratory findings showed acute kidney injury and severe metabolic acidosis. We took effective measures including endotracheal intubation and mechanical ventilation to ensure the vital signs were stable. Subsequently, we treated the patient using gastric lavage, bicarbonate, ethanol, plasmapheresis (plasma exchange), and continuous renal replacement therapy (CRRT) successfully. He gradually recovered from poisoning and was discharged without abnormalities on the 6th day. Follow-up for 3 months revealed no sequelae. Blood purification including plasmapheresis and CRRT is an effective method to scavenge toxicants from the body for acute self-poisoning with sodium ferrocyanide and methanol. Treatment strategies in the management of poisoning, multiple factors including the removal efficiency of toxin, the protection of vital organs, and the maintenance of homeostasis must be considered. PMID:26020397

  16. Plasma glucose, lactate, sodium, and potassium levels in children hospitalized with acute alcohol intoxication.

    PubMed

    Tõnisson, Mailis; Tillmann, Vallo; Kuudeberg, Anne; Väli, Marika

    2010-09-01

    The aim of our research was to study prevalence of changes in plasma levels of lactate, potassium, glucose, and sodium in relation to alcohol concentration in children hospitalized with acute alcohol intoxication (AAI). Data from 194 under 18-year-old children hospitalized to the two only children's hospital in Estonia over a 2-year period were analyzed. The pediatrician on call filled in a special form on the clinical symptoms of AAI; a blood sample was drawn for biochemical tests, and a urine sample taken to exclude narcotic intoxication. The most common finding was hyperlactinemia occurring in 66% of the patients (n=128) followed by hypokalemia (<3.5 mmol/L) in 50% (n=97), and glucose above of reference value (>6.1 mmol/L) in 40.2% of the children (n=78). Hypernatremia was present in five children. In conclusion, hyperlactinemia, hypokalemia, and glucose levels above of reference value are common biochemical findings in children hospitalized with acute AAI. PMID:20846615

  17. Downregulation of renal type IIa sodium-dependent phosphate cotransporter during lipopolysaccharide-induced acute inflammation.

    PubMed

    Ikeda, Shoko; Yamamoto, Hironori; Masuda, Masashi; Takei, Yuichiro; Nakahashi, Otoki; Kozai, Mina; Tanaka, Sarasa; Nakao, Mari; Taketani, Yutaka; Segawa, Hiroko; Iwano, Masayuki; Miyamoto, Ken-ichi; Takeda, Eiji

    2014-04-01

    The type IIa sodium-dependent phosphate cotransporter (Npt2a) plays a critical role in reabsorption of inorganic phosphate (Pi) by renal proximal tubular cells. Pi abnormalities during early stages of sepsis have been reported, but the mechanisms regulating Pi homeostasis during acute inflammation are poorly understood. We examined the regulation of Pi metabolism and renal Npt2a expression during lipopolysaccharide (LPS)-induced inflammation in mice. Dose-response and time-course studies with LPS showed significant increases of plasma Pi and intact parathyroid hormone (iPTH) levels and renal Pi excretion, while renal calcium excretion was significantly decreased. There was no difference in plasma 1,25-dihydroxyvitamin D levels, but the induction of plasma intact fibroblast growth factor 23 levels peaked 3 h after LPS treatment. Western blotting, immunostaining, and quantitative real-time PCR showed that LPS administration significantly decreased Npt2a protein expression in the brush border membrane (BBM) 3 h after injection, but there was no change in renal Npt2a mRNA levels. Moreover, tumor necrosis factor-α injection also increased plasma iPTH and decreased renal BBM Npt2a expression. Importantly, we revealed that parathyroidectomized rats had impaired renal Pi excretion and BBM Npt2a expression in response to LPS. These results suggest that the downregulation of Npt2a expression in renal BBM through induction of plasma iPTH levels alter Pi homeostasis during LPS-induced acute inflammation. PMID:24500689

  18. Hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced severe acute pancreatitis by inhibiting ROS and NF-κB pathway.

    PubMed

    Shi, Qiao; Liao, Kang-Shu; Zhao, Kai-Liang; Wang, Wei-Xing; Zuo, Teng; Deng, Wen-Hong; Chen, Chen; Yu, Jia; Guo, Wen-Yi; He, Xiao-Bo; Abliz, Ablikim; Wang, Peng; Zhao, Liang

    2015-01-01

    Hydrogen (H2), a new antioxidant, was reported to reduce (•)OH and ONOO(-) selectively and inhibit certain proinflammatory mediators to product, without disturbing metabolic redox reactions or ROS involved in cell signaling. We herein aim to explore its protective effects on acute renal injury in sodium taurocholate-induced acute pancreatitis and its possible mechanisms. Rats were injected with hydrogen-rich saline (HRS group) or normal saline (SO and SAP group) through tail intravenously (6 mL/kg) and compensated subcutaneously (20 mL/kg) after successful modeling. Results showed that hydrogen-rich saline attenuated the following: (1) serum Cr and BUN, (2) pancreatic and renal pathological injuries, (3) renal MDA, (4) renal MPO, (5) serum IL-1β, IL-6, and renal TNF-α, HMGB1, and (6) tyrosine nitration, IκB degradation, and NF-κB activation in renal tissues. In addition, it increased the level of IL-10 and SOD activity in renal tissues. These results proved that hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced acute pancreatitis, presumably because of its detoxification activity against excessive ROS, and inhibits the activation of NF-κB by affecting IκB nitration and degradation. Our findings highlight the potential value of hydrogen-rich saline as a new therapeutic method on acute renal injury in severe acute pancreatitis clinically.

  19. Hydrogen-Rich Saline Attenuates Acute Renal Injury in Sodium Taurocholate-Induced Severe Acute Pancreatitis by Inhibiting ROS and NF-κB Pathway

    PubMed Central

    Shi, Qiao; Liao, Kang-Shu; Zhao, Kai-Liang; Zuo, Teng; Deng, Wen-Hong; Chen, Chen; Yu, Jia; Guo, Wen-Yi; He, Xiao-Bo; Abliz, Ablikim; Wang, Peng; Zhao, Liang

    2015-01-01

    Hydrogen (H2), a new antioxidant, was reported to reduce •OH and ONOO− selectively and inhibit certain proinflammatory mediators to product, without disturbing metabolic redox reactions or ROS involved in cell signaling. We herein aim to explore its protective effects on acute renal injury in sodium taurocholate-induced acute pancreatitis and its possible mechanisms. Rats were injected with hydrogen-rich saline (HRS group) or normal saline (SO and SAP group) through tail intravenously (6 mL/kg) and compensated subcutaneously (20 mL/kg) after successful modeling. Results showed that hydrogen-rich saline attenuated the following: (1) serum Cr and BUN, (2) pancreatic and renal pathological injuries, (3) renal MDA, (4) renal MPO, (5) serum IL-1β, IL-6, and renal TNF-α, HMGB1, and (6) tyrosine nitration, IκB degradation, and NF-κB activation in renal tissues. In addition, it increased the level of IL-10 and SOD activity in renal tissues. These results proved that hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced acute pancreatitis, presumably because of its detoxification activity against excessive ROS, and inhibits the activation of NF-κB by affecting IκB nitration and degradation. Our findings highlight the potential value of hydrogen-rich saline as a new therapeutic method on acute renal injury in severe acute pancreatitis clinically. PMID:25878401

  20. Acute and chronic effects of sodium and potassium on the tropical freshwater cladoceran Pseudosida ramosa.

    PubMed

    Freitas, Emanuela Cristina; Rocha, Odete

    2011-01-01

    In this study, the toxicities of sodium and potassium to the tropical freshwater cladoceran Pseudosida ramosa were assessed. Acute toxicity tests on this species showed that the 48-h LC(50) of Na(+) was 556 mg l(-1), while that of K(+) was 17.7 mg l(-1). Long-term exposure of female P. ramosa to sodium reduced the total number of survivors from 10 to 6 at a concentration of 249 mg l(-1), 21-day fecundity from 20.4 to 14.3 eggs female(-1) at concentrations ranging from 72 to 249 mg l(-1), 21-day fertility from 20.1 to 6.5 neonates female(-1) at concentrations ranging from 25 to 249 mg l(-1). Furthermore, fecundity of each brood from the second to the fifth was significantly lower at 249 mg l(-1) and fertility of each brood from the first to the fifth at concentrations ranging from 25 to 249 mg l(-1). A significant decrease in fertility was associated with an increase in the number of aborted eggs. Long-term exposure to potassium decreased the 21-day fecundity of P. ramosa from 14.2 to 10.8 eggs female(-1) at a concentration of 11 mg l(-1) and fertility (fourth brood only) at 6.2 and 11 mg l(-1). Tropical reservoirs located near areas where the soil is overloaded with fertilizers and ferti-irrigation with vinasse already show concentrations of Na(+) and K(+) very close to those producing sub-lethal long-term effects on P. ramosa. A possible consequence is that organisms of the aquatic biota cannot adapt and freshwater taxa may become locally extinct, transferring dominance to salt-tolerant taxa. PMID:20978846

  1. Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2015-03-03

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Diclofenac Sodium Bolus Injection (Dyloject(TM)): A Review in Acute Pain Management.

    PubMed

    Hoy, Sheridan M

    2016-08-01

    An intravenous bolus formulation of the non-steroidal anti-inflammatory drug diclofenac sodium has been developed using hydroxypropyl-β-cyclodextrin (HPβCD) as a solubility enhancer. HPβCD diclofenac (Dyloject(TM)) is available for use in adults in the USA for the management of mild to moderate pain, and as monotherapy or in combination with opioid analgesics for the management of moderate to severe pain. In two multicentre, phase III studies in adults with acute moderate to severe postoperative pain, HPβCD diclofenac significantly reduced pain intensity and the need for rescue medication compared with placebo. In these studies, the tolerability profile of HPβCD diclofenac was generally similar to that of placebo and adverse events were mostly mild to moderate in severity. Constipation, infusion-site pain and dizziness were the most frequently reported adverse reactions occurring numerically more frequently with HPβCD diclofenac than placebo. Therapy with HPβCD diclofenac does not appear to be associated with an increased risk of cardiovascular, renal or bleeding-related adverse events versus placebo. Thus, HPβCD diclofenac extends the treatment options currently available for the management of moderate to severe postoperative pain in adults. PMID:27447189

  7. Acute toxicity of cadmium and sodium pentachlorophenate to daphnids and fish

    SciTech Connect

    Hall, W.S.; Paulson, R.L.; Hall, L.W. Jr.; Burton, D.T.

    1986-08-01

    When estimating the toxicity of effluents it is desirable to use organisms sensitive to a wide range of pollutants. Currently, the US Environmental Protection Agency (US EPA) recommends the use of Daphnia pulex, Daphnia magna, and Pimephales promelas to assess the toxicity of freshwater effluents. Ceriodaphnia sp. has also received increased attention as a standard toxicity test organism due to its sensitivity, short generation time, and ubiquitous distribution. Comparison of toxicity data generated by different investigators is often difficult because of differences in test procedures, dilution waters, or nutritional history of test organisms. The primary objectives of this research were to compare the sensitivity of Daphnia magna, Daphnia pulex, Ceriodaphnia reticulata, and Pimephales promelas to the reference toxicants CdCl/sub 2/ and sodium pentachlorophenate (NaPCP) and to compare results with those obtained by other investigators. A secondary objective of this study was to evaluate the effect of different dilution waters on the acute toxicity of these reference toxicants to the above test organisms.

  8. Protective activity of hesperidin and lipoic acid against sodium arsenite acute toxicity in mice.

    PubMed

    das Neves, Ricardo N Pires; Carvalho, Félix; Carvalho, Márcia; Fernandes, Eduarda; Soares, Elisa; de Bastos, Maria Lourdes; de Pereira, Maria Lourdes

    2004-01-01

    The objective of the present work was to evaluate the toxic effects of sodium arsenite, As(III), in mice and the protective effect of 2 antioxidants, hesperidin and lipoic acid, against the observed As(III)-induced toxicity. In each study, mice were assigned to 1 of 4 groups: control, antioxidant, antioxidant + arsenite, and arsenite. Animals were first injected with the vehicle or 25 mg antioxidant/kg BW. After 30 minutes they received an injection of 10 mg arsenite/kg BW or 0.9% NaCl. Two hours after the first injection, the liver, kidney, and testis were collected for histological evaluation. Liver samples were also taken for quantification of arsenic. In mice exposed only to As(III), various histopathological effects were observed in the liver, kidneys, and testes. In mice pretreated with either hesperidin or lipoic acid, a reduction of histopathologic effects on the liver and kidneys was observed. No protective effects were observed in the testes for either of the 2 studied antioxidants. In conclusion, hesperidin and lipoic acid provided protective effects against As(III)-induced acute toxicity in the liver and kidneys of mice. These compounds may potentially play an important role in the protection of populations chronically exposed to arsenic.

  9. Acute versus chronic supplementation of sodium citrate on 200 m performance in adolescent swimmers

    PubMed Central

    2014-01-01

    Background A double-blinded, placebo-controlled, cross-over design was used to investigate whether two different sodium citrate dihydrate (Na-CIT) supplementation protocols improve 200 m swimming performance in adolescent swimmers. Methods Ten, male swimmers (14.9 ± 0.4 years of age; 63.5 ± 4 kg) performed four 200 m time trials with the following treatments: acute (ACU) supplementation (0.5 g kg-1 administered 120 min pre-trial), acute placebo (PLC-A), chronic (CHR) supplementation (0.1 g∙kg-1 for three days and 0.3 g kg-1 on the forth day 120 min pre-trial), and chronic placebo (PLC-C). The order of the trials was randomized, with at least a six-day wash-out period between trials. Blood samples were collected by finger prick pre-ingestion, 100 min post-ingestion, and 3 min post-trial. Performance time, rate of perceived exertion, pH, base excess, bicarbonate and lactate concentration were measured. Results Post-ingestion bicarbonate and base excess were higher (P < 0.05) in both the ACU and CHR trials compared to placebo showing adequate pre-exercise alkalosis. However, performance time, rate of perceived exertion as well as post-trial pH and lactate concentration were not significantly different between trials. Further analysis revealed that five swimmers, identified as responders, improved their performance time by 1.03% (P < 0.05) and attained higher post-trial lactate concentrations in the ACU versus PLC-A trial (P < 0.05). They also had significantly higher post-trial lactate concentrations compared to the non-responders in the ACU and CHR trials. Conclusions Acute supplementation of Na-CIT prior to 200 m swimming performance led to a modest time improvement and higher blood lactate concentrations in only half of the swimmers while the chronic Na-CIT supplementation did not provide any ergogenic effect in this group of adolescent swimmers. Trial registration Clinicaltrials.gov NCT01835912. PMID:24944546

  10. Danaparoid sodium inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats

    PubMed Central

    Hagiwara, Satoshi; Iwasaka, Hideo; Hidaka, Seigo; Hishiyama, Sohei; Noguchi, Takayuki

    2008-01-01

    Introduction Systemic inflammatory mediators, including high mobility group box 1 (HMGB1), play an important role in the development of sepsis. Anticoagulants, such as danaparoid sodium (DA), may be able to inhibit sepsis-induced inflammation, but the mechanism of action is not well understood. We hypothesised that DA would act as an inhibitor of systemic inflammation and prevent endotoxin-induced acute lung injury in a rat model. Methods We used male Wistar rats. Animals in the intervention arm received a bolus of 50 U/kg of DA or saline injected into the tail vein after lipopolysaccharide (LPS) administration. We measured cytokine (tumour necrosis factor (TNF)α, interleukin (IL)-6 and IL-10) and HMGB1 levels in serum and lung tissue at regular intervals for 12 h following LPS injection. The mouse macrophage cell line RAW 264.7 was assessed following stimulation with LPS alone or concurrently with DA with identification of HMGB1 and other cytokines in the supernatant. Results Survival was significantly higher and lung histopathology significantly improved among the DA (50 U/kg) animals compared to the control rats. The serum and lung HMGB1 levels were lower over time among DA-treated animals. In the in vitro study, administration of DA was associated with decreased production of HMGB1. In the cell signalling studies, DA administration inhibited the phosphorylation of IκB. Conclusion DA decreases cytokine and HMGB1 levels during LPS-induced inflammation. As a result, DA ameliorated lung pathology and reduces mortality in endotoxin-induced systemic inflammation in a rat model. This effect may be mediated through the inhibition of cytokines and HMGB1. PMID:18380908

  11. Acute sodium bicarbonate loading has negligible effects on resting and exercise blood pressure but causes gastrointestinal distress.

    PubMed

    Kahle, Laura E; Kelly, Patrick V; Eliot, Kathrin A; Weiss, Edward P

    2013-06-01

    Oral ingestion of sodium bicarbonate (bicarbonate loading) has acute ergogenic effects on short-duration, high-intensity exercise. Because sodium bicarbonate is 27% sodium, ergogenic doses (ie, 300 mg∙kg⁻¹) result in sodium intakes well above the Dietary Reference Intakes upper limit of 2300 mg/day. Therefore, it is conceivable that bicarbonate loading could have hypertensive effects. Therefore, we performed a double-blind crossover trial to evaluate the hypothesis that bicarbonate loading increases resting and exercise blood pressure (BP). A secondary hypothesis was that bicarbonate loading causes gastrointestinal distress. Eleven endurance-trained men and women (exercise frequency, 4.6 ± 0.4 sessions/wk; duration, 65 ± 6 min/session) underwent testing on two occasions in random sequence: once after bicarbonate loading (300 mg∙kg⁻¹) and once after placebo ingestion. BP and heart rate were measured before bicarbonate or placebo consumption, 30 minutes after consumption, during 20 min of steady state submaximal cycling exercise, and during recovery. Bicarbonate loading did not affect systolic BP during rest, exercise, or recovery (P = .38 for main treatment effect). However, it resulted in modestly higher diastolic BP (main treatment effect, +3.3 ± 1.1 mmHg, P = .01) and higher heart rate (main treatment effect, +10.1 ± 2.4 beats per minute, P = .002). Global ratings of gastrointestinal distress severity (0-10 scale) were greater after bicarbonate ingestion (5.1 ± 0.5 vs 0.5 ± 0.2, P < .0001). Furthermore, 10 of the 11 subjects (91%) experienced diarrhea, 64% experience bloating and thirst, and 45% experienced nausea after bicarbonate loading. In conclusion, although a single, ergogenic dose of sodium bicarbonate does not appear to have acute, clinically important effects on resting or exercise BP, it does cause substantial gastrointestinal distress.

  12. Sodium bicarbonate infusion for prevention of acute kidney injury: no evidence for superior benefit, but risk for harm?

    PubMed

    Schiffl, Helmut

    2015-02-01

    The best "treatment" of acute kidney injury (AKI) is prevention. Patients who are at high risk of AKI should have an assessment of their volume status and receive appropriate volume expansion. The most effective type of intravenous fluid remains unclear. Innumerable studies have compared sodium bicarbonate and isotonic saline and have combined fluid hydration with pharmacological interventions, particularly N-acetyl-cysteine. However, abundant systematic reviews and meta-analyses have provided conflicting conclusions and have recognized a significant degree of heterogeneity between studies and publication bias. Most studies comparing intravenous sodium bicarbonate and saline were small. They often enrolled patients with a low risk for AKI, yielding low serious events (renal replacement therapy), and used different protocols for administration of fluids. Based on current literature, intravenous sodium bicarbonate does not seem to be more efficient than saline for the prevention of contrast-media-induced AKI, cardiac surgery-associated AKI, pigment nephropathy or septic AKI. However, some cohort studies or prospective randomized trials did track and report serious adverse events, such as higher rates of AKI or higher in-hospital mortality. At present, it should be concluded that the use of intravenous sodium bicarbonate administration to prevent AKI should be evaluated further in multicenter randomized double-blind trials rather than adopted into routine clinical practice.

  13. 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 synthesized from sucrose by Leuconostoc mesenteroides strain NRRL B-512(F). Partial depolymerization...

  14. 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 synthesized from sucrose by Leuconostoc mesenteroides strain NRRL B-512(F). Partial depolymerization...

  15. 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 synthesized from sucrose by Leuconostoc mesenteroides strain NRRL B-512(F). Partial depolymerization...

  16. 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 synthesized from sucrose by Leuconostoc mesenteroides strain NRRL B-512(F). Partial depolymerization...

  17. 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.

  18. [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.

  19. Acute Cyanide Poisoning: Hydroxocobalamin and Sodium Thiosulfate Treatments with Two Outcomes following One Exposure Event.

    PubMed

    Meillier, Andrew; Heller, Cara

    2015-01-01

    Cyanide is rapidly reacting and causes arrest of aerobic metabolism. The symptoms are diffuse and lethal and require high clinical suspicion. Remediation of symptoms and mortality is highly dependent on quick treatment with a cyanide antidote. Presently, there are two widely accepted antidotes: sodium thiosulfate and hydroxocobalamin. These treatments act on different components of cyanide's metabolism. Here, we present two cases resulting from the same source of cyanide poisoning and the use of both antidotes separately used with differing outcomes.

  20. Inhibition of glycogen synthase kinase-3β attenuates acute kidney injury in sodium taurocholate‑induced severe acute pancreatitis in rats.

    PubMed

    Zhao, Kailiang; Chen, Chen; Shi, Qiao; Deng, Wenhong; Zuo, Teng; He, Xiaobo; Liu, Tianyi; Zhao, Liang; Wang, Weixing

    2014-12-01

    The aim of the present study was to investigate the efficacy of 4‑benzyl‑2‑methyl‑1,2,4‑thiadiazolidine‑3,5‑dione (TDZD‑8), the selective inhibitor of glycogen synthase kinase‑3β (GSK‑3β), on the development of acute kidney injury in an experimental model of sodium taurocholate‑induced severe acute pancreatitis (SAP) in rats. The serum amylase, lipase, interleukin‑1β and interleukin‑6 levels, and the pancreatic pathological score were examined to determine the magnitude of pancreatitis injury. The serum creatinine and blood urea nitrogen levels, myeloperoxidase (MPO) activity and renal histological grading were measured to assess the magnitude of SAP‑induced acute kidney injury. The activation of nuclear factor‑κB (NF‑κB) was examined using an immunohistochemistry assay. The expression of GSK‑3β, phospho‑GSK‑3β (Ser9), tumour necrosis factor‑α (TNF‑α), intercellular adhesion molecule‑1 (ICAM‑1) and inducible nitric oxide synthase (iNOS) protein in the kidney was characterised using western blot analysis. TDZD‑8 attenuated (i) serum amylase, lipase and renal dysfunction; (ii) the serum concentrations of proinflammatory cytokines; (iii) pancreatic and renal pathological injury; (iv) renal MPO activity and (v) NF‑κB activation and TNF‑α, ICAM‑1 and iNOS protein expression in the kidney. The results obtained in the present study suggest that the inhibition of GSK‑3β attenuates renal disorders associated with SAP through the inhibition of NF‑κB activation and the downregulation of the expression of proinflammatory cytokines, TNF‑α, ICAM‑1 and iNOS in rats. Blocking GSK‑3β protein kinase activity may be a novel approach to the treatment of this inflammatory condition. PMID:25323773

  1. Diffusion of dextran inside microtubule sample

    NASA Astrophysics Data System (ADS)

    Prodan, Camelia

    2005-03-01

    Microtubules (Mts) are the bones of the cell. Their exterior has been extensively studied but little is known about their interior. We have studied the diffusion of fluorescein labeled dextran in the presence of GDP Mts and taxol stabilized GDP Mts. The diffusion coefficient, D, of different size dextran (10 kD, 40 kD, 70 kD, 500 kD) was measured using fluorescence recovery after photo-bleaching (FRAP). If dextran was present during the assembling of Mts, D was smaller then free diffusion coefficient. When dextran was added after the assembling, D was the same as the free diffusion coefficient. For taxol stabilized Mts (0.90 fill ratio), D was also found the same as the free diffusion coefficient .

  2. Dextransucrase and the mechanism for dextran biosynthesis.

    PubMed

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

    2008-12-01

    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

  3. Upregulation of PIAS1 protects against sodium taurocholate-induced severe acute pancreatitis associated with acute lung injury.

    PubMed

    Chen, Ping; Huang, Liya; Sun, Yunwei; Yuan, Yaozong

    2011-06-01

    The regulator of cytokine signaling known as protein inhibitor of activated STAT-1 (PIAS1) is increasingly understood to have diverse regulatory functions for inflammation, but its effect in inflammatory conditions such as severe acute pancreatitis (SAP) has not previously been reported. The aim of this study was to investigate the effect of upregulation of PIAS1 on SAP associated with acute lung injury (ALI), and its subsequent effect on disease severity. Sprague-Dawley rats were given an IV injection of adenovirus serotype 5 (Ad5)/F35-PIAS1, Ad5/F35-vector or saline before induction of SAP. The control group received only a sham operation. Lung and pancreas samples were harvested 16h after induction. The protein levels of PIAS1 in tissue were investigated. The severity of pancreatic injury was determined by a histological score of pancreatic injury, serum amylase, and pancreatic water content. The lung injury was evaluated by measurement of pulmonary microvascular permeability, lung myeloperoxidase activity and malondialdehyde levels. The survival rates of rats were also analyzed. The results found that in Ad5/F35-PIAS1 treated rats, serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 levels were decreased but showed no influence on the levels of IL-10, and the severity of pancreatic tissue injury was less compared with either untreated SAP or Ad5/F35-vector treated rats (P<0.01). The administration of Ad5/F35-PIAS1 in SAP-induced rats downregulated the activity of the signal transducer and activator of transcription-1 (STAT1) pathway and the expressions of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule (ICAM)-1 protein in lung. Thus, compared with the untreated SAP rats, the inflammatory response and the severity of ALI decreased, and the survival rates increased (P<0.01). These findings suggest that PIAS1 could augment anti-inflammatory activity by inhibiting STAT1, thus attenuating the severity of SAP associated with ALI.

  4. Sodium bicarbonate treatment prevents gastric emptying delay caused by acute exercise in awake rats.

    PubMed

    Silva, Moisés T B; Palheta-Junior, Raimundo C; Sousa, Daniel F; Fonseca-Magalhães, Patrícia A; Okoba, Willy; Campos, Caio P S; Oliveira, Ricardo B; Magalhães, Pedro J C; Santos, Armenio A

    2014-05-01

    Physical exercise, mainly after vigorous activity, may induce gastrointestinal dysmotility whose mechanisms are still unknown. We hypothesized that physical exercise and ensuing lactate-related acidemia alter gastrointestinal motor behavior. In the present study, we evaluated the effects of short-term exercise on gastric emptying rate in awake rats subjected to 15-min swimming sessions against a load equivalent to 5% of their body weight. After 0, 10, or 20 min of exercise testing, the rats were gavage fed with 1.5 ml of a liquid test meal (0.5 mg/ml of phenol red in 5% glucose solution) and euthanized 10 min postprandially to measure fractional gastric dye recovery. In addition to inducing acidemia and increasing blood lactate levels, acute exercise increased (P < 0.05) gastric retention. Such a phenomenon presented a positive correlation (P < 0.001) between blood lactate levels and fractional gastric dye recovery. Gastric retention and other acidbase-related changes were all prevented by NaHCO3 pretreatment. Additionally, exercise enhanced (P < 0.05) the marker's progression through the small intestine. In anesthetized rats, exercise increased (P < 0.05) gastric volume, measured by a balloon catheter in a barostat system. Compared with sedentary control rats, acute exercise also inhibited (P < 0.05) the contractility of gastric fundus strips in vitro. In conclusion, acute exercise delayed the gastric emptying of a liquid test meal by interfering with the acid-base balance. PMID:24557800

  5. Behavioural and gill histopathological effects of acute exposure to sodium chloride in moneda (Metynnis orinocensis).

    PubMed

    Velasco-Santamaría, Yohana M; Cruz-Casallas, Pablo E

    2008-05-01

    To evaluate the toxicity of sodium chloride (NaCl), juveniles and adult Metynnis orinocensis were exposed for 96h to 0, 5, 10, 15, 20 or 40gL(-1) of salt. Food intake, behaviour, opercular frequency (OF), mortality, body weight and gill microscopic alterations were evaluated. Behavioural changes were observed in fish exposed to concentrations higher than 10gL(-1). Juveniles and adults showed a progressive decrease in the OF and body weight. Food intake decreased in concentrations below 15gL(-1). Juveniles and adults exposed to 15, 20 or 40gL(-1) had 100% mortality. Lamellar congestion, hyperplasia and fusion were the common microscopic alterations at higher concentrations. The gill congestion severity increased with salt concentration. The LC(50) for juveniles and adults were 10.5gL(-1) and 10.8gL(-1), respectively. These results suggest that salt concentrations lower than 5gL(-1) are safe for preventive and therapeutic practices in Metynnis orinocensis; whereas prolonged exposure higher than 10gL(-1) is deleterious in this species.

  6. Neuroprotective Effects of Isosteviol Sodium Injection on Acute Focal Cerebral Ischemia in Rats

    PubMed Central

    Hu, Hui; Sun, Xiao ou; Tian, Fang; Zhang, Hao; Liu, Qing; Tan, Wen

    2016-01-01

    Previous report has indicated that isosteviol has neuroprotective effects. However, isosteviol was administered preventively before ischemia and the inclusion criteria were limited. In the present study, a more soluble and injectable form of isosteviol sodium (STVNA) was administered intravenously hours after transient or permanent middle cerebral artery occlusion (tMCAO or pMCAO) to investigate its neuroprotective effects in rats. The rats were assessed for neurobehavioral deficits 24 hours after ischemia and sacrificed for infarct volume quantification and histology evaluation. STVNA 10 mg·kg−1 can significantly reduce the infarct volumes compared with vehicle in animals subjected to tMCAO and is twice as potent as previously reported. Additionally, the therapeutic window study showed that STVNA could reduce the infarct volume compared with the vehicle group when administered 4 hours after reperfusion. A similar effect was also observed in animals treated 4 hours after pMCAO. Assessment of neurobehavioral deficits after 24 hours showed that STVNA treatment significantly reduced neurobehavioral impairments. The number of restored NeuN-labeled neurons was increased and the number of TUNEL positive cells was reduced in animals that received STVNA treatment compared with vehicle group. All of these findings suggest that STVNA might provide therapeutic benefits against cerebral ischemia-induced injury. PMID:27047634

  7. Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

    SciTech Connect

    Buehler, Paul W.; Butt, Omer I.; D'Agnillo, Felice

    2011-06-10

    Highlights: {yields} Toxicological implications associated with the use of NaNO{sub 2} therapy to treat systemic cell-free Hb exposure are not well-defined. {yields} Systemic Hb exposure followed by NaNO{sub 2} infusion induces acute CNS toxicities in guinea pigs. {yields} These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO{sub 2} alone. {yields} NaNO{sub 2}-mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO{sub 2}) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO{sub 2} with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO{sub 2} on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO{sub 2}, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO{sub 2} alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

  8. Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2012-06-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  9. Effects of dextran 70 versus crystalloids in the microcirculation of porcine hemorrhagic pancreatitis

    SciTech Connect

    Lehtola, A.; Kivilaakso, E.; Puolakkainen, P.; Karonen, S.L.; Lempinen, M.; Schroeder, T.

    1986-06-01

    The cause of hemodynamic changes occurring during acute pancreatitis remains obscure. Using a pig model of acute hemorrhagic pancreatitis and the reference sample method with 113Tin and 46 Scandium labelled microspheres, blood flow to organs was determined before and five hours after the induction of pancreatitis. Blood pressure, pulse rate and cardiac output were measured hourly. There were two treatment groups. The first group received dextran 70 (5.7 milliliters per kilogram per hour) and saline solution (7.5 milliliters per kilogram per hour) in sufficient amounts to maintain cardiac output at the initial (prepancreatic) level. The second group received saline solution (26 milliliters per kilogram per hour) only and during the experiment the cardiac output was allowed to decrease to approximately one-half of the initial level. In the dextran 70 group, blood flow in various organs stayed at the initial level or was slightly increased. However, in the saline solution group there was a marked and significant decrease in the blood flow in all organs except the antral mucosa, gallbladder and adrenal glands. The changes in the pancreatic fraction of the cardiac output during the experiment were similar to those of other organs in respective treatment groups. In conclusion, adequate infusion of dextran maintains cardiac output and organ microcirculation at the initial level during the early phase of acute hemorrhagic pancreatitis. It is suggested that the hemodynamic changes which develop during acute pancreatitis are mainly secondary to the ensuing hypovolemia and not direct consequences of the pancreatic inflammatory process.

  10. Acute toxicity of sodium formononetin-3'-sulphonate (Sul-F) in Sprague-Dawley rats and Beagle dogs.

    PubMed

    Li, Guisheng; Yang, Menglin; Hao, Xinmiao; Li, Chunmei; Gao, Yonglin; Tao, Jun

    2015-11-01

    Sodium formononetin-3'-sulphonate (Sul-F, C16H12O7SNa), a water-soluble derivate of formononetin, provided significant neuroprotective and cardioprotective effects in vitro and in vivo. The aim of this study was to evaluate acute toxicity of Sul-F after intravenous administration in rats and dogs. Animals were intravenously administered Sul-F at the maximum dosage of 2000 mg/kg and 1000 mg/kg in rats and dogs, respectively. After treatment, rats and dogs were monitored for 14 days. Body weight, clinical signs, the hematological and biochemical findings, and pathological examination were performed. The results showed that no Sul-F related clinical signs of toxicity or mortality were observed in rats. Of note, the transient vomiting was found in dogs after Sul-F administration 15-20 min. In addition, a white crystal, non-metabolic Sul-F, was found after urine volatilization in Sul-F treated animals (rats and dogs). However, neither biochemical findings nor histopathological changes due to Sul-F treatment were found in tests. In summary, the present study results provided practical guidance for selecting a safe dosage for Sul-F further studies and clinical trials in the future.

  11. Sodium selenite is a potent radioprotector of the salivary glands of the rat: acute effects on the morphology and parenchymal function during fractioned irradiation.

    PubMed

    Sagowski, C; Wenzel, S; Jenicke, L; Metternich, F U; Jaehne, M

    2005-06-01

    In vitro studies show that sodium selenite is a potential radioprotector in normal cultural cells, but not in tumor cells. The aim of this study was to evaluate the cytoprotective potency of sodium selenite during a conventional fractioned irradiation of the salivary glands of rats. The head and neck area of male WAG/RijH rats was irradiated with (60)Co-gamma rays (60 Gy/30 fractions/6 weeks). Sodium selenite (15 microg/kg body weight) was applied through a venous port 30 min before irradiation. Rats of a control group were treated in the same manner with an equal volume of physiologic sodium chloride. In the course of treatment, the salivary glands were resected at different stages and examined histopathologically. The evaluation of gland function was performed prior to and after radiotherapy by sialoscintigraphy. The irradiation caused dose-dependent damage in the salivary glands. Intra- and intercellular edema (16 Gy), vacuolization (30 Gy), degranulation (46 Gy) and necrosis of the acinar cells (60 Gy) occurred. Sodium selenite delayed the development of the described damage; additionally, the number of necrotic acinar cells after the application of 60 Gy was reduced (control, 75% vs. sodium selenite, 30%). The sialoscintigaphical results confirmed these results: the loss in gland function in the control group was 74 vs. 44% (P < 0.05) in the sodium selenite group. Based on the morphological and sialoscintigraphical findings, a cytoprotective effect on the acute toxicity of the salivary glands of rats could be detected during irradiation with synchronous application of sodium selenite. PMID:15942798

  12. The secretory response of parathyroid hormone to acute hypocalcemia in vivo is independent of parathyroid glandular sodium/potassium-ATPase activity.

    PubMed

    Martuseviciene, Giedre; Hofman-Bang, Jacob; Clausen, Torben; Olgaard, Klaus; Lewin, Ewa

    2011-04-01

    The involvement of sodium/potassium-ATPase in regulating parathyroid hormone (PTH) secretion is inferred from in vitro studies. Recently, the α-klotho-dependent rapid recruitment of this ATPase to the parathyroid cell plasma membrane in response to low extracellular calcium ion was suggested to be linked to increased hormone secretion. In this study, we used an in vivo rat model to determine the importance of sodium/potassium-ATPase in PTH secretion. Glands were exposed and treated in situ with vehicle or ouabain, a specific inhibitor of sodium/potassium-ATPase. PTH secretion was significantly increased in response to ethylene glycol tetraacetic acid-induced acute hypocalcemia and to the same extent in both vehicle and ouabain groups. The glands were removed, and inhibition of the ATPase was measured by (86)rubidium uptake, which was found to be significantly decreased in ouabain-treated parathyroid glands, indicating inhibition of the ATPase. As ouabain induced systemic hyperkalemia, the effect of high potassium on hormone secretion was also examined but was found to have no effect. Thus, inhibition of the parathyroid gland sodium/potassium-ATPase activity in vivo had no effect on the secretory response to acute hypocalcemia. Hence, the suggested importance of this ATPase in the regulation of PTH secretion could not be confirmed in this in vivo model. PMID:21209610

  13. 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.

  14. 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. PMID:25811813

  15. Effects of diclofenac sodium on the hippocampus of rats with acute subdural hematoma: histological, stereological, and molecular approach.

    PubMed

    Türkmen, A P; Kaplan, S; Aksoy, A; Altunkaynak, Bz; Yurt, Kk; Elibol, E; Çokluk, C; Onger, Me

    2016-01-01

    This study was aimed at evaluating the potential effects of acute subdural hematoma (ASDH) and diclofenac sodium (DS) therapy following ASDH on the rat hippocampus. Twenty-four male Sprague Dawley rats were used and divided into four groups. 0.1 ml of non-heparinized autologous blood from the tail vein of the animals in the non-treatment group (NTG) and treatment group (TG) was injected into the subdural space. The TG received intramuscular diclofenac sodium at a 15 mg/kg dose daily from the postoperative second hour to the seventh day after the operation. The control group (CG) and sham group (SG) were used for control and sham operations, respectively. On the postoperative eighth day, all animals were sacrificed, and the hippocampi of all animals were stereologically and histologically evaluated. Also blood samples of the animals were biochemically analyzed. As a result of the study, the mean number of neurons in CA1, CA2, and CA3 regions of the hippocampus and the total number of neurons were decreased in the hippocampus samples of the NTG and especially the TG subjects. When comparing the second blood samples, there was no difference between the levels of adrenaline and serotonin among the groups. However, after the operation, noradrenalin levels in the treatment group were found to be higher than those of the sham and control groups (p < 0.05). In the NTG and TG, histopathological findings were observed such as Nissl condensation as well as completely dead and indistinguishable neurons with abnormally shaped, shrunken cytoplasm and nuclei. Also necrotic areas on the specimens of the TG were seen. In immunohistochemical sections, c-FOS positivity was decreased in the NTG and especially the TG. Otherwise, PGC-1 positive cells were increased in the NTG and especially the TG. In this study, it was shown for the first time by means of stereological techniques that using DS after ASDH caused a decrease in the number of hippocampal neurons (CA1, CA2, and CA3

  16. Improving stability of a novel dextran-degrading enzyme from marine Arthrobacter oxydans KQ11.

    PubMed

    Wang, Delong; Lu, Mingsheng; Wang, Xiaobei; Jiao, Yuliang; Fang, Yaowei; Liu, Zhaopu; Wang, Shujun

    2014-03-15

    Dextranases can hydrolyze dextran, so they are used in the sugar industry to mitigate the milling problems associated with dextran contamination. Few studies have been carried out on the storage stability of dextranase, let alone the dextranase of Arthrobacter oxydans KQ11 isolated from sea mud samples. This study improved the storage stability of dextranase from marine A. oxydans KQ11 by adding enzymatic protective reagents (stabilizer and antiseptic). Initially, the conditions (55 °C and 30 min) for maintaining 50% dextranase activity were obtained. Then, the best stabilizers of dextranase were obtained, namely, glycerol (16%), sodium acetate (18%) and sodium citrate (20%). Results showed that p-hydroxybenzoic acid compound sodium acetate (0.05%), D-sodium isoascorbiate (0.03%), and potassium sorbate (0.05%) were the best antiseptics. Subsequent validation experiment showed that dextranase with enzymatic protective reagents maintained 70.8% and 28.96% activities at the 13th week at 25 and 37 °C, respectively. PMID:24528732

  17. Gut microbiota affects sensitivity to acute DSS-induced colitis independently of host genotype.

    PubMed

    Brinkman, Brigitta M; Becker, Anne; Ayiseh, Rene B; Hildebrand, Falk; Raes, Jeroen; Huys, Geert; Vandenabeele, Peter

    2013-11-01

    Caspase-deficient mice and wild-type (WT) mice show significant differences in their gut microbiota composition. These differences coincide with the observation that caspase-3-deficient mice carrying a natural caspase-11 mutation (Casp3/11(-/-)) are less sensitive to acute dextran sodium sulfate-induced colitis than WT mice. For these reasons, we investigated the role of the microbiota in the development of colitis by cohousing WT and Casp3/11(-/-) mice. Microbial community fingerprinting by denaturing gradient gel electrophoresis analysis revealed that the similarities in gut microbial composition of WT and Casp3/11(-/-) mice increased after cohousing. In the acute dextran sodium sulfate-induced colitis model, Casp3/11(-/-) mice that were cohoused with WT mice showed increased weight loss and disease activity scores and increased neutrophil infiltration and inflammatory cytokine levels in their colon tissue compared with Casp3/11(-/-) mice that were not cohoused with WT mice. Also, we demonstrate that only the microbiota of the Casp3/11(-/-) mice cohoused with WT mice showed an important increase in Prevotella species. In conclusion, our cohousing experiments revealed that the colitogenic activity of the WT microbiota is transferable to Casp3/11(-/-) mice and that Prevotella species are likely to be involved. By contrast, the relative protection of Casp3/11(-/-) mice against dextran sodium sulfate damage is not transferred to WT mice after cohousing. These results underscore the need for in-depth studies of the bilateral interaction of host genes and microbiota to gain insight into the mechanisms of disease pathogenesis. Our findings also have important implications for the experimental design of disease studies in genetically modified mice and conclusions drawn from them. PMID:24105395

  18. Characterization of collagenous meshworks by volume exclusion of dextrans.

    PubMed Central

    Bert, J L; Pearce, R H; Mathieson, J M; Warner, S J

    1980-01-01

    The volumes from which 3H-labelled dextrans are excluded by dermal collagenous fibres were calculated by dilution of dextran probes. Five dextrans, of average Stokes' radii 1.72, 2.53, 3.92, 4.54 and 14.24nm, were investigated at concentrations between 0.1 and 3% (w/w). The excluded volume was dependent on dextran concentration only for the two smaller probes. The largest dextran was shown not to bind to the fibres. A plot of the square root of excluded volume against Stokes' radius was linear for the four smallest dextrans, corresponding to the predictions of Ogston's [(1958) Trans. Faraday Soc. 54, 1754--1757] rod-and-sphere model of fibrous exclusion, and suggesting that dextrans of Stokes' radius between 1.72 and 4.54 nm were excluded by a cylindrical solid fibre of radius 2.90 +/- 0.72 nm. Larger molecules were excluded by a structure of much greater size, since the volume exclusion for the largest dextran was only slightly greater than that of the dextran less than one-third its radius. The excluded volume of 3H2O fell slightly below the line describing the dextran data, indicating that water had access to most of the volume not occupied by the collagenous fibres. PMID:6169339

  19. Electrospun polyurethane-dextran nanofiber mats loaded with Estradiol for post-menopausal wound dressing.

    PubMed

    Unnithan, Afeesh Rajan; Sasikala, Arathyram Ramachandra Kurup; Murugesan, Priya; Gurusamy, Malarvizhi; Wu, Dongmei; Park, Chan Hee; Kim, Cheol Sang

    2015-01-01

    Post-menopausal wound care management is a substantial burden on health services, since there are an increased number of elderly populations linked with age-related delayed wound healing. The controlled estrogen replacement can accelerate healing of acute cutaneous wounds, linked to its potent anti-inflammatory activity. The electrospinning technique can be used to introduce the desired therapeutic agents to the nanofiber matrix. So here we introduce a new material for wound tissue dressing, in which a polyurethane-dextran composite nanofibrous wound dressing material loaded with β-estradiol was obtained through electrospinning. Dextran can promote neovascularization and skin regeneration in chronic wounds. This study involves the characterization of these nanofibers and analysis of cell growth and proliferation to determine the efficiency of tissue regeneration on these biocomposite polymer nanofibrous scaffolds and to study the possibility of using it as a potential wound dressing material in the in vivo models. PMID:25748849

  20. Role of serum sodium in assessing hospital mortality in cancer patients with spontaneous tumour lysis syndrome inducing acute uric acid nephropathy.

    PubMed

    Hsu, H-H; Chen, Y-C; Tian, Y-C; Chan, Y-L; Kuo, M-C; Tang, C-C; Fang, J-T; Lee, S-Y; Yang, C-W

    2009-05-01

    Spontaneous tumour lysis syndrome (STLS) inducing acute uric acid nephropathy, a rare and neglected disease, presents more insidiously than conventional post-treatment tumour lysis syndrome. Although STLS is a serious and potentially fatal complication in patients with neoplastic disorders, few investigations have addressed the relevance of clinical and laboratory features in assessing prognosis. A retrospective study was conducted, reviewing the records of all patients who developed acute renal failure (ARF) at Chang Gung memorial hospital between 1 July 1999 and 30 June 2003. STLS-induced acute uric acid nephropathy was identified in 12 of 1072 ARF patients (1.1%) during the study period. All patients had advanced stage tumours with large tumour burden, and 66.7% of cases had abdominal organ involvement. All 12 hyperuricemic patients became oliguric despite conservative therapy, and remained hyperuricemic (21.6 +/- 5.2 mg/dl) before dialysis therapy. Diuresis developed in eight patients (66.7%), with associated resolution of hyperuricemia, azotemia and metabolic derangements following dialysis initiation. Overall hospital mortality was 58.3%. Death in most patients was related to hyponatremia and hypoalbuminemia on admission. The serum sodium was found to have the best Youden index (0.86) and highest overall prediction accuracy (93%). Moreover, serum sodium and serum albumin for individual patients were significantly and positively correlated (r = 0.617, p = 0.032). This investigation confirms a grave prognosis for cancer patients with STLS inducing acute uric acid nephropathy. Hyponatremia and hypoalbuminemia on the first day of admission indicate poor prognosis in such patients.

  1. The acute renal actions of angiotensin converting enzyme inhibitors in the sodium-depleted conscious primate are mediated by inhibition of the renin-angiotensin system.

    PubMed

    Humke, U; Levens, N; Wood, J; Hofbauer, K

    1992-01-01

    The purpose of this study was to determine if the changes in renal function acutely produced by an inhibitor of angiotensin converting enzyme (ACE) in the sodium-depleted conscious marmoset can be explained primarily by blockade of the renin-angiotensin system. Intravenous injection of a dose of the ACEI, enalaprilate (2 mg/kg), that produced a maximal lowering of blood pressure (BP), also decreased renal vascular resistance and increased renal blood flow. Glomerular filtration rate was unchanged by enalaprilat, leading to a fall in the filtration fraction. In comparison, a dose of the renin inhibitory monoclonal antibody, R-3-36-16 (0.1 mg/kg), that also produced a maximal fall in BP, produced similar changes in renal hemodynamics to those observed after administration of the ACEI. Combined administration of 2 mg/kg enalaprilat and 0.1 mg/kg R-3-36-16 produced changes in BP and renal hemodynamics similar to those produced by the same doses of either agent administered alone. Enalaprilat (2 mg/kg) significantly increased urine volume (UV) and urinary sodium excretion (UNaV). In contrast, these parameters were not significantly altered by 0.1 mg/kg R-3-36-16. However, when given at a 10-fold higher dose, the monoclonal antibody produced an increase in UNaV and UV identical to that produced by the ACEI alone. Enalaprilat did not increase UV and UNaV excretion to a greater extent than the high dose of the renin inhibitory antibody. These results demonstrate that acute administration of an ACEI affects BP and renal function in the sodium-depleted conscious primate primarily by inhibition of the renin-angiotensin system.

  2. Development of dextran nanoparticles for stabilizing delicate proteins

    NASA Astrophysics Data System (ADS)

    Wu, Fei; Zhou, Zhihua; Su, Jing; Wei, Liangming; Yuan, Weien; Jin, Tuo

    2013-04-01

    One of the most challenging problems in the development of protein pharmaceuticals is to deal with stabilities of proteins due to its complicated structures. This study aims to develop a novel approach to stabilize and encapsulate proteins into dextran nanoparticles without contacting the interface between the aqueous phase and the organic phase. The bovine serum albumin, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), β-galactosidase, and myoglobin were selected as model proteins. The proteins were added into an aqueous solution containing the dextran and polyethylene glycol, and then encapsulated into dextran nanoparticles by aqueous-aqueous freezing-induced phase separation. The encapsulation efficiency and recovery of dextran nanoparticles were determined. The dextran nanoparticles loaded with proteins were characterized by scanning electron microscopy and particle size analysis. The protein aggregation was determined by size-exclusion chromatography-high-performance chromatography, and the bioactivity of proteins recovered during formulation steps was determined. The bioactivity of GM-CSF, G-CSF, and β-galactosidase were examined by the proliferation of TF-1 cell, NSF-60 cell, and ortho-nitrophenyl- β-galactoside assay, respectively. The results of bioactivity recovered show that this novel dextran nanoparticle can preserve the protein's bioactivity during the preparation process. LysoSensor™ Yellow/Blue dextran, a pH-sensitive indicator with fluorescence excited at two channels, was encapsulated into dextran nanoparticles to investigate the ability of dextran nanoparticles to resist the acidic microenvironment (pH < 2.5). The result shows that the dextran nanoparticles attenuate the acidic microenvironment in the poly (lactic-co-glycolic acid) microsphere by means of the dilution effect. These novel dextran nanoparticles provided an appealing approach to stabilize the delicate proteins for

  3. How Strong Is the Evidence for Sodium Bicarbonate to Prevent Contrast-Induced Acute Kidney Injury After Coronary Angiography and Percutaneous Coronary Intervention?

    PubMed Central

    Dong, Yuhao; Zhang, Bin; Liang, Long; Lian, Zhouyang; Liu, Jing; Liang, Changhong; Zhang, Shuixing

    2016-01-01

    Abstract 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

  4. 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

  5. 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

  6. 21 CFR 520.1182 - Iron dextran suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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. (a) Specifications. Each milliliter (mL) of suspension contains 55.56 milligrams (mg) iron as...

  7. 21 CFR 520.1182 - Iron dextran suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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. (a) Specifications. Each milliliter (mL) of suspension contains 55.56 milligrams (mg) iron as...

  8. 21 CFR 520.1182 - Iron dextran suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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. (a) Specifications. Each milliliter (mL) of suspension contains 55.56 milligrams (mg) iron as...

  9. 21 CFR 520.1182 - Iron dextran suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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. (a) Specifications. Each milliliter (mL) of suspension contains 55.56 milligrams (mg) iron as...

  10. 21 CFR 520.1182 - Iron dextran suspension.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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. (a) Specifications. Each milliliter (mL) of suspension contains 55.56 milligrams (mg) iron as...

  11. Studies of DEAE-dextran-mediated gene transfer.

    PubMed

    Yang, Y W; Yang, J C

    1997-02-01

    DEAE-dextran-mediated gene transfer was studied for the introduction of pSV2neo DNA into Fisher-rat 3T3 (FR3T3) cells. Zeta (zeta) potentials of the DEAE-dextran-DNA complexes and FR3T3 cells were found to be dependent on the concentration of DEAE-dextran in the medium. The maximum transfection efficiency occurred at a DEAE-dextran/DNA ratio of 50:1 or thereabouts. The interaction between DNA and cells is determined by the adsorption process. The results obtained, along with the correlation between the kinetic adsorption behaviour of 3H-labelled DNA and the transfection efficiency, indicated that adsorption of DEAE-dextran-DNA complexes to the negatively charged cell surfaces, due to electrostatic and dispersion attraction, plays the decisive role in determining the DNA transfection efficiencies.

  12. Structure and antioxidant activity of soy protein isolate-dextran conjugates obtained by TiO2 photocatalysis.

    PubMed

    Jin, Bei; Zhou, Xiaosong; Li, Bing; Chen, Caiyan; Zhang, Xiaosa; Chen, Siqiao

    2015-01-01

    The aim of this study was to investigate the structural characteristics and antioxidant activities of soy protein isolate- (SPI-) dextran conjugates obtained by TiO2 photocatalysis treatment. Results revealed that the UV-vis absorption and the fluorescence intensity increased as the photocatalytic power increased (P < 0.05). Higher photocatalytic power could promote the extent of glycation and the formation of high molecular weight SPI-dextran conjugates, which were evidenced by free amino group content and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The Fourier transform infrared (FT-IR) spectra suggested that the amide I, II, and III bands of SPI were altered by the glycation induced by TiO2 photocatalysis. Moreover, significant changes of secondary structure occurred in SPI-dextran conjugates. The α-helix, β-sheet, β-turns, and random coil were changed from approximately 10.6%, 37.9%, 12.9%, and 38.6% to 3.8%, 10.4%, 17.7%, and 68.8%, respectively, after treatment at photocatalytic power of 1000 W. In addition, SPI-dextran conjugates obtained by TiO2 photocatalysis treatment exhibited high hydroxyl radical scavenging activity and possessed increased reducing power. All data indicated that TiO2 photocatalysis was an efficient method for promoting protein-polysaccharide copolymerisation.

  13. Structure and antioxidant activity of soy protein isolate-dextran conjugates obtained by TiO2 photocatalysis.

    PubMed

    Jin, Bei; Zhou, Xiaosong; Li, Bing; Chen, Caiyan; Zhang, Xiaosa; Chen, Siqiao

    2015-01-01

    The aim of this study was to investigate the structural characteristics and antioxidant activities of soy protein isolate- (SPI-) dextran conjugates obtained by TiO2 photocatalysis treatment. Results revealed that the UV-vis absorption and the fluorescence intensity increased as the photocatalytic power increased (P < 0.05). Higher photocatalytic power could promote the extent of glycation and the formation of high molecular weight SPI-dextran conjugates, which were evidenced by free amino group content and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The Fourier transform infrared (FT-IR) spectra suggested that the amide I, II, and III bands of SPI were altered by the glycation induced by TiO2 photocatalysis. Moreover, significant changes of secondary structure occurred in SPI-dextran conjugates. The α-helix, β-sheet, β-turns, and random coil were changed from approximately 10.6%, 37.9%, 12.9%, and 38.6% to 3.8%, 10.4%, 17.7%, and 68.8%, respectively, after treatment at photocatalytic power of 1000 W. In addition, SPI-dextran conjugates obtained by TiO2 photocatalysis treatment exhibited high hydroxyl radical scavenging activity and possessed increased reducing power. All data indicated that TiO2 photocatalysis was an efficient method for promoting protein-polysaccharide copolymerisation. PMID:26495283

  14. Structure and Antioxidant Activity of Soy Protein Isolate-Dextran Conjugates Obtained by TiO2 Photocatalysis

    PubMed Central

    Jin, Bei; Zhou, Xiaosong; Li, Bing; Chen, Caiyan; Zhang, Xiaosa; Chen, Siqiao

    2015-01-01

    The aim of this study was to investigate the structural characteristics and antioxidant activities of soy protein isolate- (SPI-) dextran conjugates obtained by TiO2 photocatalysis treatment. Results revealed that the UV-vis absorption and the fluorescence intensity increased as the photocatalytic power increased (P < 0.05). Higher photocatalytic power could promote the extent of glycation and the formation of high molecular weight SPI-dextran conjugates, which were evidenced by free amino group content and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The Fourier transform infrared (FT-IR) spectra suggested that the amide I, II, and III bands of SPI were altered by the glycation induced by TiO2 photocatalysis. Moreover, significant changes of secondary structure occurred in SPI-dextran conjugates. The α-helix, β-sheet, β-turns, and random coil were changed from approximately 10.6%, 37.9%, 12.9%, and 38.6% to 3.8%, 10.4%, 17.7%, and 68.8%, respectively, after treatment at photocatalytic power of 1000 W. In addition, SPI-dextran conjugates obtained by TiO2 photocatalysis treatment exhibited high hydroxyl radical scavenging activity and possessed increased reducing power. All data indicated that TiO2 photocatalysis was an efficient method for promoting protein-polysaccharide copolymerisation. PMID:26495283

  15. Acute Sodium Arsenite-Induced Hematological and Biochemical Changes in Wistar Rats: Protective Effects of Ethanol Extract of Ageratum conyzoides

    PubMed Central

    Ola-Davies, Olufunke Eunice; Akinrinde, Akinleye Stephen

    2016-01-01

    Background: Ageratum conyzoides L. (Asteraceae) is an annual herbaceous plant used in folklore medicine for the treatment of a wide range of diseases. Objective: To investigate the protective effect of the ethanol leaf extract of A. conyzoides (EEAC) against hematological, serum biochemical and histological alterations induced by Sodium arsenite administration to Wistar rats. Materials and Methods: Twenty male Wistar rats were randomly assigned into four groups of five rats each. Group I received propylene glycol and Group II rats were given the (EEAC, 100 mg/kg b.w.) orally for 7 days. Group III were given a single oral dose of sodium arsenite (NaAsO2, 2.5 mg/kg b.w.). Animals in Group IV were pretreated with 100 mg/kg EEAC for 7 days followed by a single oral dose of sodium arsenite. Results: Arsenic exposure resulted in significant reductions (P < 0.05) in values of packed cell volume (PCV), hemoglobin concentration (Hb) and red blood cell (RBC) count, and elevation in total white blood cell (WBC) count with insignificant reductions in serum total protein, albumin, and globulin levels. Alterations in aspartate aminotransferase, alanine transferase, alkaline phosphatase, and gamma glutamyl transferase activities, as well as in serum levels of urea, creatinine, glucose, cholesterol, and triglyceride levels, were not statistically significant. EEAC significantly restored (P < 0.05) the PCV, Hb, RBC, and WBC as well as serum albumin, globulin, and total protein to normal values. Conclusion: The results of this study indicate that EEAC possess strong potentials to protect against toxicities induced by sodium arsenite. SUMMARY Ageratum conyzoides produced significant reversal of the reduction in the erythrocytic indices (packed cell volume, red blood cell, and Hb) caused by sodium arseniteSodium arsenite-induced slight elevations in serum aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), correlating with the

  16. Cost-effectiveness impact of iron dextran on hemodialysis patients' use of epoetin alfa and blood.

    PubMed

    Driver, P S

    1998-12-15

    The cost-effectiveness impact of iron dextran administration on the use of epoetin alfa and blood in hemodialysis patients was studied. Subjects were ambulatory hemodialysis patients who had been receiving hemodialysis for at least six months before the start of an iron dextran protocol and who had been given epoetin alfa for at least four of those six months. Clinical data were collected for six months before and six months after the protocol was implemented. Successful treatment was defined as a hematocrit of 33-36%, a transferrin saturation of >10%, a ferritin concentration of >100 ng/mL, and no blood use except for acute blood loss. A total of 33 patients completed the study. Fifty units of blood were used in the first six months and nine units in the second six months. There was significant improvement in mean hematocrit, ferritin, and transferrin saturation values after the protocol began. Average epoetin alfa doses did not change significantly. There was significant improvement in success rates for ferritin and blood use and in the overall success rate. Ten patients met all success criteria in the preprotocol period, versus 27 in the postprotocol period. Monthly cost-effectiveness analysis for the preprotocol and postprotocol periods indicated costs of $1350 and $526, per successful treatment, respectively. The incremental cost-effectiveness of iron dextran was $42 per successful treatment. Iron dextran improved iron indices and reduced the need for blood transfusions but did not reduce the average dose of epoetin alfa. The additional cost of therapy per month seemed justified by the clinical benefits.

  17. Acute and chronic effects of sodium tungstate on an aquatic invertebrate (Daphnia magna), green alga (Pseudokirchneriella subcapitata), and zebrafish (Danio rerio).

    PubMed

    Clements, Leslie N; Lemus, Ranulfo; Butler, Alicia D; Heim, Kate; Rebstock, Matthew R; Venezia, Carmen; Pardus, Michael

    2012-10-01

    Although aquatic toxicity data exists for tungstate substances, insufficient data of high quality and relevancy are available for conducting an adequate risk assessment. Therefore, a series of acute and chronic toxicity tests with sodium tungstate (Na(2)WO(4)) were conducted on an aquatic invertebrate (Daphnia magna), green alga (Pseudokirchneriella subcapitata), and zebrafish (Danio rerio). Collectively, the data from these studies suggest that sodium tungstate exhibits a relatively low toxicity to these taxa under these test conditions. All studies were conducted in the same laboratory under good laboratory practice standards using Organisation for Economic Co-operation and Development guidelines with the same stock of test material and the same analytical methods. All results are reported as mg W/L. The following toxicity values were based on mean measured concentrations. For D. magna, the 21 day test no-observable effect concentration (NOEC) was 25.9 mg W/L, and the 48-h median effective concentration (EC(50)) from the acute test was >95.5 mg W/L (the highest concentration tested). The P. subcapitata test yielded an ErC(50) of 31 mg W/L. A 38-day test with zebrafish resulted in an NOEC ≥5.74 mg W/L with no effects at any concentration. The 96-h LC(50) from the acute test with zebrafish was >106 mg W/L. The results of the current acute study for daphnids and fish are consistent with published literature, whereas the algae results are different from previously reported values. Transformation/dissolution (T/D) studies, which were conducted according to United Nations Globally Harmonized System of Classification and Labelling of Chemicals protocol, confirmed that the WO (4) (-2) anion accounted for most of the tungsten in solution. For classification purposes, the algae ecotoxity reference value was then compared with T/D data and would not classify Na(2)WO(4) as an aquatic toxicant under the European Union Classification, Labelling and Packaging scheme. PMID

  18. Acute and chronic effects of sodium tungstate on an aquatic invertebrate (Daphnia magna), green alga (Pseudokirchneriella subcapitata), and zebrafish (Danio rerio).

    PubMed

    Clements, Leslie N; Lemus, Ranulfo; Butler, Alicia D; Heim, Kate; Rebstock, Matthew R; Venezia, Carmen; Pardus, Michael

    2012-10-01

    Although aquatic toxicity data exists for tungstate substances, insufficient data of high quality and relevancy are available for conducting an adequate risk assessment. Therefore, a series of acute and chronic toxicity tests with sodium tungstate (Na(2)WO(4)) were conducted on an aquatic invertebrate (Daphnia magna), green alga (Pseudokirchneriella subcapitata), and zebrafish (Danio rerio). Collectively, the data from these studies suggest that sodium tungstate exhibits a relatively low toxicity to these taxa under these test conditions. All studies were conducted in the same laboratory under good laboratory practice standards using Organisation for Economic Co-operation and Development guidelines with the same stock of test material and the same analytical methods. All results are reported as mg W/L. The following toxicity values were based on mean measured concentrations. For D. magna, the 21 day test no-observable effect concentration (NOEC) was 25.9 mg W/L, and the 48-h median effective concentration (EC(50)) from the acute test was >95.5 mg W/L (the highest concentration tested). The P. subcapitata test yielded an ErC(50) of 31 mg W/L. A 38-day test with zebrafish resulted in an NOEC ≥5.74 mg W/L with no effects at any concentration. The 96-h LC(50) from the acute test with zebrafish was >106 mg W/L. The results of the current acute study for daphnids and fish are consistent with published literature, whereas the algae results are different from previously reported values. Transformation/dissolution (T/D) studies, which were conducted according to United Nations Globally Harmonized System of Classification and Labelling of Chemicals protocol, confirmed that the WO (4) (-2) anion accounted for most of the tungsten in solution. For classification purposes, the algae ecotoxity reference value was then compared with T/D data and would not classify Na(2)WO(4) as an aquatic toxicant under the European Union Classification, Labelling and Packaging scheme.

  19. Complete remission of nephrotic syndrome and acute kidney injury in crescentic IgA nephropathy: Role of mycophenolate sodium

    PubMed Central

    Bhandari, D.; Jhaveri, K. D.; Shah, H. H.

    2016-01-01

    Optimal therapy and prognosis of crescentic-IgA nephropathy (C-IgAN) are not known. Reported treatment options for C-IgAN include combination of corticosteroids and cyclophosphamide for 6 months. The role of mycophenolate sodium in C-IgAN is unknown. We report a case of C-IgAN that was successfully treated with combination immunosuppressive therapy. PMID:27795634

  20. Enhanced ELISA based on carboxymethylated dextran coatings.

    PubMed

    Liberelle, Benoît; Fortier, Charles; De Crescenzo, Gregory

    2014-01-01

    In a "sandwich" enzyme-linked immunosorbent assay (ELISA) designed to detect an antigen in a complex protein mixture, the antigen is usually captured via an antibody adsorbed to the wells of a microplate. Plate preparation for standard assay involves a passive adsorption of capture antibodies followed by the incubation of blocking agents. Here, we describe a new strategy that replaces these two time-consuming adsorption steps (up to 15 h) by a unique step corresponding to the covalent grafting of the capture antibody on a carboxymethylated dextran (CMD) layer, a single step completed in 15 min. Taking advantage of the CMD low-fouling properties, blocking agent-free buffer solutions can be used as diluent in the improved approach.

  1. Nanoparticles of hydrophobically modified dextrans as potential drug carrier systems.

    PubMed

    Aumelas, A; Serrero, A; Durand, A; Dellacherie, E; Leonard, M

    2007-09-01

    Nanoparticles combining a hydrophobically modified dextran core and a polysaccharide surface coverage were elaborated. Their suitability for applications like drug delivery was evaluated. The selected polysaccharide, dextran, was chemically modified by the covalent attachment of hydrocarbon groups (aliphatic or aromatic) via the formation of ether links. According to the extent of modification, either water-soluble or water-insoluble dextran derivatives were obtained. The latter exhibited solubility in organic solvents like tetrahydrofuran or dichloromethane saturated with water. Water-soluble dextran derivatives were used as polymeric surfactants for the control of nanoparticles surface characteristics. Nanoparticles were prepared either by o/w emulsion or solvent-diffusion methods. The size and surface properties of dextran nanoparticles were correlated to processing conditions. The stability of colloidal suspensions was examined as a function of ionic strength and related to the particle surface characteristics. The redispersability of freeze-dried suspensions without the addition of cryoprotectant was demonstrated. Finally, the degradability of modified dextrans was compared to that of starting dextran, after enzymatic hydrolysis in the presence of dextranase.

  2. Synthesis and spectroscopic characterization of copper(H)-dextran complexes

    NASA Astrophysics Data System (ADS)

    Mitić, Ž.; Nikolić, G. S.; Cakić, M.; Nikolić, R.; Ilić, Lj.

    2007-09-01

    Synthesis of stable copper(II) complexes with reduced dextran derivatives can be realized with low molar polysaccharides of an average molar mass 5000 g mol-1. A copper(II) content of 4 20% is achieved at pH 7 8 and at the boiling point. Copper(II) complex formation with dextran was analyzed by spectrophotometric VIS methods. The IR spectra of copper(II) complexes with dextran were analyzed to find the most stable conformation of the glucopyranose unit. The ESR parameters of the spectrum indicate a square-planar coordination of the Cu(II) ion with four oxygen ligand atoms in the same plane. Copper deficiency causes a number of pathological states [1]. In both human and veterinary medicine, commercial copper preparations based on dextran and its derivatives are used for such purposes [2]. According to the literature data, dextran has the ability of complex formation with various biometals (Zn, Fe, Co, Ca, and Mg) [3 6]. Iron complexes with different polysaccharides have special importance and they have been described in detail [7]. Synthetic procedures for the complex formation of Cu(II) with polysaccharides, including dextran, are described in scientific and patent literature [8]. However, literature data on the complex formation possibility of the Cu(II) ion with dextran derivatives are scarce.

  3. The heart communicates with the kidney exclusively through the guanylyl cyclase-A receptor: acute handling of sodium and water in response to volume expansion.

    PubMed Central

    Kishimoto, I; Dubois, S K; Garbers, D L

    1996-01-01

    Disruption of guanylyl cyclase-A (GC-A) results in mice displaying an elevated blood pressure, which is not altered by high or low dietary salt. However, atrial natriuretic peptide (ANP), a proposed ligand for GC-A, has been suggested as critical for the maintenance of normal blood pressure during high salt intake. In this report, we show that infusion of ANP results in substantial natriuresis and diuresis in wild-type mice but fails to cause significant changes in sodium excretion or urine output in GC-A-deficient mice. ANP, therefore, appears to signal through GC-A in the kidney. Other natriuretic/diuretic factors could be released from the heart. Therefore, acute volume expansion was used as a means to cause release of granules from the atrium of the heart. That granule release occurred was confirmed by measurements of plasma ANP concentrations, which were markedly elevated in both wild-type and GC-A-null mice. After volume expansion, urine output as well as urinary sodium and cyclic GMP excretion increased rapidly and markedly in wild-type mice, but the rapid increases were abolished in GC-A-deficient animals. These results strongly suggest that natriuretic/diuretic factors released from the heart function exclusively through GC-A. PMID:8650246

  4. Successful Use of Hydroxocobalamin and Sodium Thiosulfate in Acute Cyanide Poisoning: A Case Report with Follow-up.

    PubMed

    Zakharov, Sergey; Vaneckova, Manuela; Seidl, Zdenek; Diblik, Pavel; Kuthan, Pavel; Urban, Pavel; Navratil, Tomas; Pelclova, Daniela

    2015-09-01

    Hydroxocobalamin is an effective first-line antidote used mainly in monotherapy of cyanide poisonings, while the opinions are different on the effects of its combination with sodium thiosulfate. A 58-year-old male committed a suicide attempt by ingesting of 1200-1500 mg of potassium cyanide; he was unconscious for 1-1.5 min. after ingestion with the episode of generalized seizures. On admission to the ICU, the patient was acidotic (pH 7.28; HCO3 14.0 mmol/L, base excess -12.7 mmol/L, saturation O2 0.999) with high serum lactate (12.5 mmol/L). Hydroxocobalamin was administered 1.5 hr after ingestion in two subsequent intravenous infusions at a total dose of 7.5 g. The infusion was followed by continuous intravenous administration of 1 mL/hr/kg of 10% sodium thiosulfate at a total dose of 12 g. No complications and adverse reactions were registered. Serum lactate decreased to 0.6 mmol/L the same day, and arterial blood gases became normal (pH 7.49; HCO3 27.2 mmol/L, base excess 2.2 mmol/L, saturation O2 0.994). The follow-up examination 5 months later revealed no damage of basal ganglia and cerebellum on magnetic resonance imaging. The neurological examination revealed no pathological findings. On the ocular coherence tomography, the retinal nerve fibres layer was normal. In visual evoked potentials, there was a normal evoked complex on the left eye and minor decrease in amplitude on the right eye. Combination of hydroxocobalamin and sodium thiosulfate can have a positive effect on the survival without long-term neurological and visual sequelae in the cases of massive cyanide poisonings due to the possibility of a potentiation or synergism of hydroxocobalamin effects by sodium thiosulfate. This synergism can be explained by the different time-points of action of two antidotes: the initial and immediate effect of hydroxocobalamin, followed by the delayed, but more persistent effect of sodium thiosulfate.

  5. Biophysical basis of hypoxic radioprotection by deoxygenated dextran-hemoglobin

    SciTech Connect

    Wong, J.T.; Hill, R.P.

    1986-08-01

    Perfusion with deoxygenated dextran-hemoglobin provides an effective method for inducing hypoxic radioprotection of normal tissues during radiation treatment of tumors. In this study, the dependence of P50, the half-saturation pressure of oxygen binding to dextran-hemoglobin, was analyzed as a function of solution temperature and pH. The variation of attainable radioprotection with P50, and with the amount of collateral blood entering into the perfused region, was calculated. Upon perfusion of canine gracilis muscle with deoxygenated dextran-hemoglobin, a rapid onset of extensive venous hypoxia was observed.

  6. Upper airway obstruction resulting from acute mucosal injury induced by direct ingestion of sodium picosulfate/magnesium citrate powder

    PubMed Central

    Kim, Gyeong Bo; Hwang, Sung Yeon; Shin, Tae Gun; Lee, Tae Rim; Cha, Won Chul; Sim, Min Seob; Jo, Ik Joon; Song, Keun Jeong; Rhee, Joong Eui; Jeong, Yeon Kwon

    2016-01-01

    A 59-year-old man presented to the emergency department with a chief complaint of sore throat after swallowing sodium picosulfate/magnesium citrate powder for bowel preparation, without first dissolving it in water. The initial evaluation showed significant mucosal injury involving the oral cavity, pharynx, and epiglottis. Endotracheal intubation was performed for airway protection in the emergency department, because the mucosal swelling resulted in upper airway compromise. After conservative treatment in the intensive care unit, he underwent tracheostomy because stenosis of the supraglottic and subglottic areas was not relieved. The tracheostomy tube was successfully removed after confirming recovery, and he was discharged 3 weeks after admission. PMID:27752627

  7. Effects of acute sodium fluoride exposure on kidney function, water homeostasis, and renal handling of calcium and inorganic phosphate.

    PubMed

    Santoyo-Sanchez, Mitzi Paola; del Carmen Silva-Lucero, Maria; Arreola-Mendoza, Laura; Barbier, Olivier Christophe

    2013-06-01

    Fluoride compounds are abundant and widely distributed in the environment at a variety of concentrations. Further, fluoride induces toxic effects in target organs such as the liver and kidney. In this study, we performed an early analysis of renal function using a clearance technique in Wistar rats acutely exposed to fluoride at a plasma concentration of 0.625 μg/ml. Our results revealed that fluoride, at a concentration close to the concentration present in the serum after environmental exposure, induced a significant tubular dysfunction, resulting in diluted urine, impaired protein reabsorption, and increased calcium and phosphate urinary excretion. Our work demonstrates that even acute exposures to low concentrations of NaF may induce renal damage and confirms that, after exposure, the kidney participates directly in the calcium and phosphate deficiencies observed in fluoride-exposed populations.

  8. Dapagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, Acutely Reduces Energy Expenditure in BAT via Neural Signals in Mice

    PubMed Central

    Chiba, Yumiko; Yamada, Tetsuya; Tsukita, Sohei; Takahashi, Kei; Munakata, Yuichiro; Shirai, Yuta; Kodama, Shinjiro; Asai, Yoichiro; Sugisawa, Takashi; Uno, Kenji; Sawada, Shojiro; Imai, Junta; Nakamura, Kazuhiro; Katagiri, Hideki

    2016-01-01

    Selective sodium glucose cotransporter-2 inhibitor (SGLT2i) treatment promotes urinary glucose excretion, thereby reducing blood glucose as well as body weight. However, only limited body weight reductions are achieved with SGLT2i treatment. Hyperphagia is reportedly one of the causes of this limited weight loss. However, the effects of SGLT2i treatment on systemic energy expenditure have not been fully elucidated. Herein, we investigated the acute effects of dapagliflozin, a SGLT2i, on systemic energy expenditure in mice. Eighteen hours after dapagliflozin treatment oxygen consumption and brown adipose tissue (BAT) expression of ucp1, a thermogenesis-related gene, were significantly decreased as compared to those after vehicle treatment. In addition, dapagliflozin significantly suppressed norepinephrine (NE) turnover in BAT and c-fos expression in the rostral raphe pallidus nucleus (rRPa) which contains the sympathetic premotor neurons responsible for thermogenesis. These findings indicate that the dapagliflozin-mediated acute decrease in energy expenditure involves a reduction in BAT thermogenesis via decreased sympathetic nerve activity from the rRPa. Furthermore, common hepatic branch vagotomy abolished the reductions in ucp1 expression and NE contents in BAT and c-fos expression in the rRPa. In addition, alterations in hepatic carbohydrate metabolism, such as decreases in glycogen contents and upregulation of phosphoenolpyruvate carboxykinase, manifested prior to the suppression of BAT thermogenesis, e.g. 6 hours after dapagliflozin treatment. Collectively, these results suggest that SGLT2i treatment acutely suppresses energy expenditure in BAT via regulation of an inter-organ neural network consisting of the common hepatic vagal branch and sympathetic nerves. PMID:26963613

  9. Dapagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, Acutely Reduces Energy Expenditure in BAT via Neural Signals in Mice.

    PubMed

    Chiba, Yumiko; Yamada, Tetsuya; Tsukita, Sohei; Takahashi, Kei; Munakata, Yuichiro; Shirai, Yuta; Kodama, Shinjiro; Asai, Yoichiro; Sugisawa, Takashi; Uno, Kenji; Sawada, Shojiro; Imai, Junta; Nakamura, Kazuhiro; Katagiri, Hideki

    2016-01-01

    Selective sodium glucose cotransporter-2 inhibitor (SGLT2i) treatment promotes urinary glucose excretion, thereby reducing blood glucose as well as body weight. However, only limited body weight reductions are achieved with SGLT2i treatment. Hyperphagia is reportedly one of the causes of this limited weight loss. However, the effects of SGLT2i treatment on systemic energy expenditure have not been fully elucidated. Herein, we investigated the acute effects of dapagliflozin, a SGLT2i, on systemic energy expenditure in mice. Eighteen hours after dapagliflozin treatment oxygen consumption and brown adipose tissue (BAT) expression of ucp1, a thermogenesis-related gene, were significantly decreased as compared to those after vehicle treatment. In addition, dapagliflozin significantly suppressed norepinephrine (NE) turnover in BAT and c-fos expression in the rostral raphe pallidus nucleus (rRPa) which contains the sympathetic premotor neurons responsible for thermogenesis. These findings indicate that the dapagliflozin-mediated acute decrease in energy expenditure involves a reduction in BAT thermogenesis via decreased sympathetic nerve activity from the rRPa. Furthermore, common hepatic branch vagotomy abolished the reductions in ucp1 expression and NE contents in BAT and c-fos expression in the rRPa. In addition, alterations in hepatic carbohydrate metabolism, such as decreases in glycogen contents and upregulation of phosphoenolpyruvate carboxykinase, manifested prior to the suppression of BAT thermogenesis, e.g. 6 hours after dapagliflozin treatment. Collectively, these results suggest that SGLT2i treatment acutely suppresses energy expenditure in BAT via regulation of an inter-organ neural network consisting of the common hepatic vagal branch and sympathetic nerves. PMID:26963613

  10. Irritancy testing in occupational dermatology: comparison between two quick tests and the acute irritation induced by sodium lauryl sulphate.

    PubMed

    Bangha, E; Hinnen, U; Elsner, P

    1996-11-01

    To reduce the incidence of irritant contact dermatitis, the development of screening methods to identify subjects with increased susceptibility to irritants is essential. In a pilot study on the comparison between two quick, non-invasive irritancy tests (dimethyl sulfoxide (DMSO) and sodium hydroxide (NaOH) with the time-consuming patch testing with sodium lauryl sulphate (SLS), no correlation between the "quick tests" and SLS patch testing was observed. In the present paper the results of irritancy testing in 181 metal worker trainees are presented. Experimental irritant contact dermatitis reactions were induced on the medial third of the volar forearm using SLS 0.5%, applied for 23 h and as "quick tests" DMSO 90% and 95% and a solution of 0.2% mol/l NaOH applied for 5 min. Assessment of skin irritability was made by visual scoring and measurement of transepidermal water loss. Except for a statistically significant relationship between the irritations by DMSO 90% and 95%, correlations between the different techniques were weak or non-existent. This is most probably due to different pathophysiological pathways for the irritant reactions. We therefore propose to use a spectrum of different tests in occupational dermatology for predicting the individual's risk of irritant contact dermatitis.

  11. Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate) as an antidote for acute uranium intoxication in mice

    SciTech Connect

    Basinger, M.A.; Jones, M.M.

    1981-11-01

    Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate) administered intraperitoneally was found to antagonize the lethal action of intraperitoneally induced uranium(VI) toxicity. In a comparative study Tiron was evaluated against Na3CaDTPA (sodium calcium diethylenetriaminepentaacetate). The ability of these compounds to detoxify the uranyl ion in simple and complexed form and their efficacy in delayed treatment regimens and determined. Toxicities of the complexes were assessed by the administration of uranyl acetate at levels of 40 mg/kg or 80 mg/kg complexed at a mole ratio of 3:1 or 2:1 of chelating agent to uranium, prior to injection, followed by two additional doses of chelating agent given one and three hours later at a 10:1 mole ratio of chelating agent to uranium. Therapy in delayed treatment regimens consisted of three injections of antidote given 20 minutes, one hour, and three hours, at a 10:1 mole ratio of chelating agent to uranium, subsequent to an injection of 40 mg/kg uranyl acetate. Survival rates for animals receiving multiple injections of Tiron were enhanced over those receiving Na3CaDTPA. The low inherent toxicity of Tiron may make it appropriate for possible clinical application.

  12. 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

  13. 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

  14. Acute toxicity of sodium metabisulphite in larvae and post-larvae of the land crab, Cardisoma guanhumi.

    PubMed

    Galli, Orlando B S; Fujimoto, Rodrigo Y; Abrunhosa, Fernando A

    2012-08-01

    Sodium metabisulphite (SMB) is used in marine shrimp aquaculture to prevent the occurrence of black spot. The release SMB into the estuarine environment from shrimp farm pond effluents has been reported. This study evaluated the susceptibility of larvae and post-larvae of land crab, Cardisoma guanhumi to this salt. A decrease in dissolved oxygen and pH occurred with increasing concentration of SMB and exposure time. LC(50) values after 48 h of exposure were 34 ± 1.1 mg/L, 31.1 ± 1.9 mg/L, and 30.6 ± 0.5 mg/L for I zoea larvae, megalopa larvae and stage I juveniles, respectively.

  15. Lacticemia After Acute Overdose of Metformin in an Adolescent Managed Without Intravenous Sodium Bicarbonate or Extracorporeal Therapy.

    PubMed

    Bebarta, Vikhyat S; Pead, Joshua; Varney, Shawn M

    2015-08-01

    Metformin-associated lactic acidosis or lacticemia has been widely reported as an adverse drug effect in diabetic patients with other significant comorbidities and in acute overdose in adults. Lacticemia has been reported twice in a previously healthy pediatric population, both of which were suicide attempts and required hemodialysis. We report a case of a 17-year-old, nondiabetic, healthy adolescent girl with metformin-associated lacticemia who intentionally overdosed on metformin, had no coingestants, and was treated only with crystalloids. Furthermore, she did not require intravenous bicarbonate administration or extracorporeal removal. PMID:26241713

  16. Dextran and gelatin based photocrosslinkable tissue adhesive.

    PubMed

    Wang, Tao; Nie, Jun; Yang, Dongzhi

    2012-11-01

    A two-component tissue adhesive based on biocompatible and bio-degradable polymers (oxidized urethane dextran (Dex-U-AD) and gelatin) was prepared and photocrosslinked under the ultraviolet (UV) irradiation. The adhesive could adhere to surface of gelatin, which simulated the human tissue steadily. The structures of above Dex-U-AD were characterized by FTIR, (1)H NMR spectroscopy and XRD. The adhesion property of result products was evaluated by lap-shear test. The maximum adhesion strength could reach to 4.16±0.72 MPa which was significantly higher than that of fibrin glue. The photopolymerization process of Dex-U-AD/gelatin was monitored by real time infrared spectroscopy (RTIR). It took less than 5 min to complete the curing process. The cytotoxicity of Dex-U-AD/gelatin also was evaluated which indicated that Dex-U-AD/gelatin gels were nontoxic to L929 cell. The relationship between all the above-mentioned properties and degree of oxidization of Dex-U-AD was assessed. The obtained products have the potential to serve as tissue adhesive in the future.

  17. Spectroscopic study of copper(II) complexes with carboxymethyl dextran and dextran sulfate

    NASA Astrophysics Data System (ADS)

    Glišić, S.; Nikolić, G.; Cakić, M.; Trutić, N.

    2015-07-01

    The copper(II) ion complexes with carboxymethyl dextran (CMD) and dextran sulfate (DS) were studied by different methods. Content of copper was determined by atomic absorption spectroscopy. It was found that copper : ligand mole ratio (Cu : CMD) is 1 : 2, and Cu : DS is 1 : 1 by mole ratio method. Spectrophotometric parameters of synthesized compounds are characteristic for Cu(II) ion in octahedral ( O h ) coordination. Analyzing of FTIR spectra in ν(C=O) vibration region has showed that -COOH group acts as bidentate ligand, while the compounds of Cu(II) with DS copper ions are in the region of four oxygen atoms of two adjacent sulfo groups. The presence of crystalline water was determined by isotopic substitution of H2O molecules with D2O molecules. Comparison of spectra recorded at room (RT) and liquid nitrogen temperature (LNT) has enabled detection bands of water molecules libration indicating that they are coordinated complementing coordination sphere of Cu(II) ions to six. The complexes are of Cu(II) · (CMD)2 · (H2O)2 or Cu(II) · DS · (H2O)2 type. The similarities of the γ(C-H) range in a part of FTIR spectra indicate that there is no difference in the conformation of the 4 C 1 glucopyranose (Glc) unit CMD and DS synthesized Cu(II) complexes.

  18. Assessment of skin irritancy by 2 short tests compared to acute irritation induced by sodium lauryl sulfate.

    PubMed

    Hinnen, U; Elsner, P; Burg, G

    1995-10-01

    Irritant contact dermatitis is a very common disease that is preventable by protective measures. The development of screening methods to identify subjects with increased susceptibility to irritants is essential to reduce the incidence of this disorder in the workplace. On the outlook for such methods, 2 quick non-invasive tests for irritability of the skin were compared to reliable, but time-consuming, patch testing with sodium lauryl sulfate (SLS). In 20 healthy volunteers, 0.5% SLS was applied on the medial 1.3 of the forearm for 23 h in order to induce experimental irritant contact dermatitis. On the same part of the forearm, 3 concentrations of dimethylsulfoxide (DMSO) and a solution of 0.2 mol/l NaOH were applied for 5 min. Assessment of skin irritability was made by visual scoring and measurement of transepidermal water loss. No correlation between the "quick tests" and SLS patch testing was found, indicating that these tests assess different mechanisms of irritation.

  19. 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.

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

    PubMed

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

    2013-11-15

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

  1. Sex-specific transcriptional responses of the zebrafish (Danio rerio) brain selenoproteome to acute sodium selenite supplementation

    PubMed Central

    Benner, Maia J.; Settles, Matt L.; Murdoch, Gordon K.; Hardy, Ronald W.

    2013-01-01

    The potential benefits of selenium (Se) supplementation are currently under investigation for prevention of certain cancers and treatment of neurological disorders. However, little is known concerning the response of the brain to increased dietary Se under conditions of Se sufficiency, despite the majority of Se supplementation trials occurring in healthy, Se sufficient subjects. We evaluated the transcriptional response of Se-dependent genes, selenoproteins and the genes necessary for their synthesis (the selenoproteome), in the zebrafish (Danio rerio) brain to supplementation with nutritionally relevant levels of dietary Se (sodium selenite) during conditions of assumed Se sufficiency. We first used a microarray approach to analyze the response of the brain selenoproteome to dietary Se supplementation for 14 days and then assessed the immediacy and time-scale transcriptional response of the brain selenoproteome to 1, 7, and 14 days of Se supplementation by quantitative real-time PCR (qRT-PCR). The microarray approach did not indicate large-scale influences of Se on the brain transcriptome as a whole or the selenoproteome specifically; only one nonselenoproteome gene (si:ch73-44m9.2) was significantly differentially expressed. Our qRT-PCR results, however, indicate that increases of dietary Se cause small, but significant transcriptional changes within the brain selenoproteome, even after only 1 day of supplementation. These responses were dynamic over a short period of supplementation in a manner highly dependent on sex and the duration of Se supplementation. In nutritional intervention studies, it may be necessary to utilize methods such as qRT-PCR, which allow larger sample sizes, for detecting subtle transcriptional changes in the brain. PMID:23737534

  2. Acute Δ9-tetrahydrocannabinol blocks gastric hemorrhages induced by the nonsteroidal anti-inflammatory drug diclofenac sodium in mice

    PubMed Central

    Kinsey, Steven G.; Cole, Erica C.

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs), which are among the most widely used analgesics in the world, cause gastrointestinal inflammation that is potentially life-threatening. Although inhibitors of endocannabinoid catabolic enzymes protect against gastropathy in fasted NSAID-treated mice, the gastroprotective effects of Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, have yet to be investigated. Male C57BL/6J mice were fasted, administered vehicle or Δ9-THC (.01–50 mg/kg; oral or intraperitoneal), and then treated with the NSAID diclofenac sodium (100 mg/kg, p.o.) to induce gastric lesions. In separate groups of mice, the cannabimimetic behavioral effects of Δ9-THC given via each route of administration were compared using a battery of tests, consisting of assessment of locomotor activity, nociception in the tail withdrawal test, catalepsy in the bar test, and hypothermia. Δ9-THC dose-dependently attenuated diclofenac-induced gastric hemorrhagic streaks through both p.o. and i.p. routes of administration (ED50 (95% confidence interval) = 0.64 (0.26 – 1.55) mg/kg and 0.06 (0.01 – 0.34) mg/kg, respectively). Δ9-THC given i.p. was 2–3 orders of magnitude more potent in reducing diclofenac-induced gastric ulcers than in producing locomotor immobility, antinociception, hypothermia, and catalepsy, while the potency of ratio of p.o. Δ9-THC between each behavior measure was 7–18. These data indicate that the phytocannabinoid Δ9-THC protects against diclofenac-induced gastric inflammatory tissue damage at doses insufficient to cause common cannabinoid side effects. PMID:23769745

  3. Acute Δ(9)-tetrahydrocannabinol blocks gastric hemorrhages induced by the nonsteroidal anti-inflammatory drug diclofenac sodium in mice.

    PubMed

    Kinsey, Steven G; Cole, Erica C

    2013-09-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs), which are among the most widely used analgesics in the world, cause gastrointestinal inflammation that is potentially life-threatening. Although inhibitors of endocannabinoid catabolic enzymes protect against gastropathy in fasted NSAID-treated mice, the gastroprotective effects of Δ(9)-tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, have yet to be investigated. Male C57BL/6J mice were fasted, administered vehicle or Δ(9)-THC (.01-50mg/kg; oral or intraperitoneal), and then treated with the NSAID diclofenac sodium (100mg/kg, p.o.) to induce gastric lesions. In separate groups of mice, the cannabimimetic behavioral effects of Δ(9)-THC given via each route of administration were compared using a battery of tests, consisting of assessment of locomotor activity, nociception in the tail withdrawal test, catalepsy in the bar test, and hypothermia. Δ(9)-THC dose-dependently attenuated diclofenac-induced gastric hemorrhagic streaks through both p.o. and i.p. routes of administration (ED50 (95% confidence interval)=0.64 (0.26-1.55)mg/kg and 0.06 (0.01-0.34) mg/kg, respectively). Δ(9)-THC given i.p. was 2-3 orders of magnitude more potent in reducing diclofenac-induced gastric ulcers than in producing locomotor immobility, antinociception, hypothermia, and catalepsy, while the potency of ratio of p.o. Δ(9)-THC between each behavior measure was 7-18. These data indicate that the phytocannabinoid Δ(9)-THC protects against diclofenac-induced gastric inflammatory tissue damage at doses insufficient to cause common cannabinoid side effects.

  4. Efficacy of a Solution Composed by Verbascoside, Polyvinylpyrrolidone (PVP) and Sodium Hyaluronate in the Treatment of Chemotherapy-induced Oral Mucositis in Children With Acute Lymphoblastic Leukemia.

    PubMed

    Bardellini, Elena; Amadori, Francesca; Schumacher, Richard Fabian; D'Ippolito, Carmelita; Porta, Fulvio; Majorana, Alessandra

    2016-10-01

    The aim of this study was to assess the efficacy of a solution composed by verbascoside, polyvinylpyrrolidone, and sodium hyaluronate (Mucosyte) in the treatment of chemotherapy-induced oral mucositi (OM). Patients between 5 and 18 years receiving chemotherapy for acute lymphoblastic leukemia and with OM grade 1 or 2 were randomized in group A (treated with Mucosyte, 3 mouthwashes/d per 8 d) and group B (treated with placebo, ie, an inert water-based solution, 3 mouthwashes/d per 8 d). The OM scoring was performed at day 1 (diagnosis of OM-T0), after 3 days of treatment (T1), and at day 8 (T2). Pain was evaluated through the visual analog scale with the same timing of OM measurement. A total of 56 patients were included (28 patients per group). Group A experienced a statistically significant decline of OM at T2 (P=0.0038); a statistically significant difference in pain reduction between 2 groups both at T1 and at T2 (P<0.005) was observed. The use of Mucosyte mouthwashes in children with chemotherapy-induced OM may be recommended as supportive therapy. PMID:27571124

  5. Anti-hygroscopic effect of dextrans in herbal formulations.

    PubMed

    Tong, Henry H Y; Wong, Sammas Y S; Law, Marcus W L; Chu, Kevin K W; Chow, Albert H L

    2008-11-01

    Equilibrium moisture sorptions of two dried aqueous herbal extracts and their mixtures with dextrans of various molecular weights were investigated as a function of relative humidity at ambient temperature, and the data were analyzed by both the Guggenheim-Anderson-deBoer (GAB) and Brunauer-Emmett-Teller (BET) equations. Glass transition temperatures (T(g)) of the samples were measured by differential scanning calorimetry, and their dependence on the moisture contents of the extracts was analyzed by the linear, Fox and expanded Gordon-Taylor mathematical models. All dextran-extract mixtures exhibited single T(g) values, indicating that they existed as single homogeneous phases. The BET equation was found adequate for description of the moisture sorption isotherms for all samples. The dextrans appeared to reduce the hygroscopicity of the herbal extracts solely by a dilution effect. The observed increase in T(g) and accompanying decrease in tackiness of the herbal extracts in the presence of dextrans may be explained by the ability of dextrans to restrict the molecular mobility of simple sugars and to counteract the plasticizing effect of water in the extracts. The expanded Gordon-Taylor equation has proved useful in predicting the T(g) of hygroscopic amorphous herbal mixtures. PMID:18706495

  6. Anti-hygroscopic effect of dextrans in herbal formulations.

    PubMed

    Tong, Henry H Y; Wong, Sammas Y S; Law, Marcus W L; Chu, Kevin K W; Chow, Albert H L

    2008-11-01

    Equilibrium moisture sorptions of two dried aqueous herbal extracts and their mixtures with dextrans of various molecular weights were investigated as a function of relative humidity at ambient temperature, and the data were analyzed by both the Guggenheim-Anderson-deBoer (GAB) and Brunauer-Emmett-Teller (BET) equations. Glass transition temperatures (T(g)) of the samples were measured by differential scanning calorimetry, and their dependence on the moisture contents of the extracts was analyzed by the linear, Fox and expanded Gordon-Taylor mathematical models. All dextran-extract mixtures exhibited single T(g) values, indicating that they existed as single homogeneous phases. The BET equation was found adequate for description of the moisture sorption isotherms for all samples. The dextrans appeared to reduce the hygroscopicity of the herbal extracts solely by a dilution effect. The observed increase in T(g) and accompanying decrease in tackiness of the herbal extracts in the presence of dextrans may be explained by the ability of dextrans to restrict the molecular mobility of simple sugars and to counteract the plasticizing effect of water in the extracts. The expanded Gordon-Taylor equation has proved useful in predicting the T(g) of hygroscopic amorphous herbal mixtures.

  7. Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction

    PubMed Central

    Simon, Marc A.; Vanderpool, Rebecca R.; Nouraie, Mehdi; Bachman, Timothy N.; White, Pamela M.; Sugahara, Masataka; Gorcsan, John; Parsley, Ed L.; Gladwin, Mark T.

    2016-01-01

    BACKGROUND. Pulmonary hypertension (PH) is associated with poor outcomes, yet specific treatments only exist for a small subset of patients. The most common form of PH is that associated with left heart disease (Group 2), for which there is no approved therapy. Nitrite has shown efficacy in preclinical animal models of Group 1 and 2 PH, as well as in patients with left heart failure with preserved ejection fraction (HFpEF). We evaluated the safety and efficacy of a potentially novel inhaled formulation of nitrite in PH-HFpEF patients as compared with Group 1 and 3 PH. METHODS. Cardiopulmonary hemodynamics were recorded after acute administration of inhaled nitrite at 2 doses, 45 and 90 mg. Safety endpoints included change in systemic blood pressure and methemoglobin levels. Responses were also compared with those administered inhaled nitric oxide. RESULTS. Thirty-six patients were enrolled (10 PH-HFpEF, 20 Group 1 pulmonary arterial hypertension patients on background PH-specific therapy, and 6 Group 3 PH). Drug administration was well tolerated. Nitrite inhalation significantly lowered pulmonary, right atrial, and pulmonary capillary wedge pressures, most pronounced in patients with PH-HFpEF. There was a modest decrease in cardiac output and systemic blood pressure. Pulmonary vascular resistance decreased only in Group 3 PH patients. There was substantial increase in pulmonary artery compliance, most pronounced in patients with PH-HFpEF. CONCLUSIONS. Inhaled nitrite is safe in PH patients and may be efficacious in PH-HFpEF and Group 3 PH primarily via improvements in left and right ventricular filling pressures and pulmonary artery compliance. The lack of change in pulmonary vascular resistance likely may limit efficacy for Group 1 patients. TRIAL REGISTRATION. ClinicalTrials.gov NCT01431313 FUNDING. This work was supported in part by the NIH grants P01HL103455 (to MAS and MTG), R01HL098032 (to MTG), and R01HL096973 (to MTG), and Mast Therapeutics, Inc. PMID

  8. Sodium Bicarbonate

    MedlinePlus

    ... pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking sodium bicarbonate, call your doctor. ... your body. If you are on a sodium-restricted diet, check with your doctor before taking sodium bicarbonate.

  9. 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.

  10. Differences in activation of mouse hepcidin by dietary iron and parenterally administered iron dextran: compartmentalization is critical for iron sensing.

    PubMed

    Daba, Alina; Gkouvatsos, Konstantinos; Sebastiani, Giada; Pantopoulos, Kostas

    2013-01-01

    The iron regulatory hormone hepcidin responds to both oral and parenteral iron. Here, we hypothesized that the diverse iron trafficking routes may affect the dynamics and kinetics of the hepcidin activation pathway. To address this, C57BL/6 mice were administered an iron-enriched diet or injected i.p. with iron dextran and analyzed over time. After 1 week of dietary loading with carbonyl iron, mice exhibited significant increases in serum iron and transferrin saturation, as well as in hepatic iron, Smad1/5/8 phosphorylation and bone morphogenetic protein 6 (BMP6), and hepcidin mRNAs. Nevertheless, hepcidin expression reached a plateau afterward, possibly due to upregulation of inhibitory Smad7, Id1, and matriptase-2 mRNAs, while hepatic and splenic iron continued to accumulate over 9 weeks. One day following parenteral administration of iron dextran, mice manifested elevated serum and hepatic iron levels and Smad1/5/8 phosphorylation, but no increases in transferrin saturation or BMP6 mRNA. Surprisingly, hepcidin failed to appropriately respond to acute overload with iron dextran, and a delayed (after 5-7 days) hepcidin upregulation correlated with increased transferrin saturation, partial relocation of iron from macrophages to hepatocytes, and induction of BMP6 mRNA. Our data suggest that the physiological hepcidin response is saturable and are consistent with the idea that hepcidin senses exclusively iron compartmentalized within circulating transferrin and/or hepatocytes.

  11. 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

    ...% Dextran 70 and 0.9% NaCl or/5% Dextrose 500 mL Glass Bottle) held by Hospira, Inc., 275 North Field Dr...% Dextran 70 and 0.9% NaCl or/5% Dextrose 500 mL Glass Bottle) under the process in Sec. 314.150(c)(21 CFR..., approval of NDA 080- 819, DEXTRAN 70 [6% Dextran 70 and 0.9% NaCl or/5% Dextrose 500 mL Glass Bottle],...

  12. Acute toxicity of sodium bicarbonate, a major component of coal bed natural gas produced waters, to 13 aquatic species as defined in the laboratory

    USGS Publications Warehouse

    Harper, David D.; Farag, Aida M.; Skaar, Don

    2014-01-01

    Water produced during coal bed natural gas (CBNG) extraction in the Powder River Structural Basin of Wyoming and Montana (USA) may contain concentrations of sodium bicarbonate (NaHCO3) of more than 3000 mg/L. The authors evaluated the acute toxicity of NaHCO3, also expressed as bicarbonate (HCO3−), to 13 aquatic organisms. Of the 13 species tested, 7 had a median lethal concentration (LC50) less than 2000 mg/L NaHCO3, or 1300 mg/L HCO3−. The most sensitive species were Ceriodaphnia dubia, freshwater mussels (Lampsilis siliquoidea), pallid sturgeon (Scaphirhynchus albus), and shovelnose sturgeon (Scaphirhynchus platorynchus). The respective LC50s were 989 mg/L, 1120 mg/L, 1249 mg/L, and 1430 mg/L NaHCO3, or 699 mg/L, 844 mg/L, 831 mg/L, and 1038 mg/L HCO3−. Age affected the sensitivity of fathead minnows, even within life stage. Two days posthatch, fathead minnows were more sensitive to NaHCO3 and HCO3− compared with 4-d-old fish, even though fish up to 14 d old are commonly used for toxicity evaluations. The authors recommend that ion toxicity exposures be conducted with organisms less than 24 h posthatch to ensure that experiments document the most sensitive stage of development. The results of the present study, along with historical and current research regarding the toxicity of bicarbonate, may be useful to establish regulatory standards for HCO3−.

  13. Acute toxicity of sodium bicarbonate, a major component of coal bed natural gas produced waters, to 13 aquatic species as defined in the laboratory.

    PubMed

    Harper, David D; Farag, Aïda M; Skaar, Don

    2014-03-01

    Water produced during coal bed natural gas (CBNG) extraction in the Powder River Structural Basin of Wyoming and Montana (USA) may contain concentrations of sodium bicarbonate (NaHCO3) of more than 3000 mg/L. The authors evaluated the acute toxicity of NaHCO3, also expressed as bicarbonate (HCO3(-)), to 13 aquatic organisms. Of the 13 species tested, 7 had a median lethal concentration (LC50) less than 2000 mg/L NaHCO3, or 1300 mg/L HCO3(-). The most sensitive species were Ceriodaphnia dubia, freshwater mussels (Lampsilis siliquoidea), pallid sturgeon (Scaphirhynchus albus), and shovelnose sturgeon (Scaphirhynchus platorynchus). The respective LC50s were 989 mg/L, 1120 mg/L, 1249 mg/L, and 1430 mg/L NaHCO3, or 699 mg/L, 844 mg/L, 831 mg/L, and 1038 mg/L HCO3(-). Age affected the sensitivity of fathead minnows, even within life stage. Two days posthatch, fathead minnows were more sensitive to NaHCO3 and HCO3(-) compared with 4-d-old fish, even though fish up to 14 d old are commonly used for toxicity evaluations. The authors recommend that ion toxicity exposures be conducted with organisms less than 24 h posthatch to ensure that experiments document the most sensitive stage of development. The results of the present study, along with historical and current research regarding the toxicity of bicarbonate, may be useful to establish regulatory standards for HCO3(-). This article is a US Government work and is in the public domain in the USA.

  14. 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.

  15. Measurement of plasma volume by means of 59Fe-labelled dextran and Evans blue compared.

    PubMed

    Wilson, R J; Mills, I H

    1970-05-01

    The apparent volumes of distribution of Evans blue and (59)Fe-dextran were determined in 18 studies.(59)Fe-dextran volume was 5% lower than Evans blue volume, a highly significant difference. The rate of loss of (59)Fe dextran from the circulation was significantly less than that of Evans blue.

  16. Measurement of plasma volume by means of 59Fe-labelled dextran and Evans blue compared

    PubMed Central

    Wilson, R. J.; Mills, Ivor H.

    1970-01-01

    The apparent volumes of distribution of Evans blue and 59Fe-dextran were determined in 18 studies. 59Fe-dextran volume was 5% lower than Evans blue volume, a highly significant difference. The rate of loss of 59Fe dextran from the circulation was significantly less than that of Evans blue. PMID:4914280

  17. Cationic, amphiphilic dextran nanomicellar clusters as an excipient for dry powder inhaler formulation.

    PubMed

    Vadakkan, Mithun Varghese; Binil Raj, S S; Kartha, Chandrasekharan C; Vinod Kumar, G S

    2015-09-01

    Effective delivery of drugs to alveoli in a controlled manner using hydrophobic polymers as carriers has already been reported. Preclinical studies revealed that toxicity and hydrophobicity are related to each other in pulmonary delivery. Here, we are reporting a chemically modified dextran having amphiphilicity and cationicity achieved by controlled grafting of stearyl amine. Two proportions of lipopolymers were synthesized and physico-chemical characterization was carried out. In vivo evaluation of sub-acute toxicity of the synthesized lipopolymer in Sprague-Dawley rats was carried out for three months. This was followed by a histological evaluation of the sacrificed animal's lung. Further, the synthesized lipopolymer was formulated with drug (Rifampicin) loaded inhalable microparticles through spray drying. The final drug formulation was tested for toxicity and proinflammatory responses in human cell lines. Dose deposition efficiency of the formulation was determined using Anderson Cascade Impactor. PMID:26013041

  18. Studies on acyclovir-dextran conjugate: synthesis and pharmacokinetics.

    PubMed

    Tu, Jiasheng; Zhong, Sha; Li, Pengmei

    2004-01-01

    Acyclovir is an antivirus drug which has a good in vitro activity against hepatitis B virus. But because of the low solubility and low distribution in liver, the clinical application of acyclovir in hepatitis B was limited. To increase the solubility and the distribution in liver, acyclovir-dextran conjugate was synthesized by formation of Schiff's base. The solubility of obtained conjugate was 12 times greater than free acyclovir. Acyclovir will be slowly released from the obtained conjugate in pH 7.4 phosphate buffer solution (PBS) at 37 degrees C with a rate constant of 0.0035 hr(-1). Pharmacokinetic studies of acyclovir and acyclovir-dextran conjugate were conducted in mice by i.v. administration. Acyclovir concentrations in plasma, liver and kidney were determined by HPLC method. Relatively higher distribution of acyclovir in liver was observed when i.v. acyclovir-dextran conjugate as compared with i.v. free acyclovir. The results of pharmacokinetic studies indicated that acyclovir-dextran conjugate will be a good candidate to treat hepatitis B. PMID:15554220

  19. 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.

  20. 99mTc-dextran-antibody conjugates. Labelling procedures.

    PubMed

    Márquez, M; Westlin, J E; Nilsson, S; Holmberg, A R

    1996-01-01

    Dextran forms stable chelates with 99mTc, a radionuclide with ideal properties for planar scintigraphic and tomographic imaging. This study investigates some of the factors of importance to the formation of 99mTc-dextran. The complex was used for the technetium labelling of a monoclonal antibody. Two radiolabelling methods were studied: direct dextran labelling with the reductant dissolved in HCI and labelling via a weak 'transfer' chelator (tartaric acid) with the reductant dissolved in ethanol. Different conditions during the labelling reaction were studied. Finally, dextran was coupled to a monoclonal anticytokeratin antibody and the conjugate was subsequently radiolabelled with 99mTc. Gel filtration (GFR) and thin layer chromatography (TLC) were compared as methods for estimation of the labelling efficiency. When using 10-500 microM of ligand, 5-100 microM SnCl2 with 10-500 MBq of technetium at pH 7 incubated for 10-15 min, the radiolabelling seemed optimal (70-75% labelling efficiency). It was found that 100 microM tartaric acid used as a weak intermediate chelator with SnCl2 dissolved in ethanol improved the reproducibility of the labelling. The labelling efficiency was not affected by either the presence of oxygen or the addition of an oxygen scavenger during the labelling incubation. In general, TLC showed higher labelling efficiencies than GFR, indicating inadequate separation of the different moieties.

  1. Oscillatory and steady shear rheology of gellan/dextran blends.

    PubMed

    Ahmad, Nurul Hawa; Ahmed, Jasim; Hashim, Dzulkifly M; Manap, Yazid Abdul; Mustafa, Shuhaimi

    2015-05-01

    Oscillatory and steady shear rheology of gellan (G) and dextran (D) solution individually, and in blends (G/D ratio 1:1, 1:2, and 1:3 w/v) with a total hydrocolloid concentration of 3 % (w/v) were studied at 25 °C. Individually, 1.5 % dextran and 1.5 % gellan in solution exhibited Newtonian and non-Newtonian behavior, respectively. A blend of equal proportion of dextran and gellan (G/D = 1:1) exhibits a distinct gel point (G' = G″), and further addition of dextran in the blend (G/D = 1:2 and 1:3) resulted predominating liquid-like (G″ > G') behavior. A plot of G' vs G″ distinctly showed the gradual transition of the blend. Shear stress (τ)-shear rate ([Formula: see text]) data fitted well the Herschel-Bulkley model. The G/D blend exhibited shear thinning behavior with flow behavior index less than unity. The Cox-Merz rule did not fit well for the complex shear viscosity (η*) and apparent viscosity (η) of the blend. PMID:25892789

  2. Hydrodynamic chromatography using flow of a highly concentrated dextran solution through a coiled tube.

    PubMed

    Miyagawa, Yoichi; Morisada, Shintaro; Ohto, Keisuke; Hidetaka, Kawakita

    2016-08-01

    Separation of colloidal particles in non-Newtonian fluid is important in food engineering. Using hydrodynamic chromatography, colloidal particles and starch granules originating from corn were individually injected into dextran solutions (Mw 2,000,000g/mol) flowing through a coiled tube for efficient size separation. Rheological properties of dextran solutions ranging from 50 to 250g/L were determined, revealing pseudoplastic fluid behavior. Velocity profiles for dextran solution flow in coiled tubes were obtained from rheological power law parameters. Suspensions of colloidal particles of diameters 1.0 and 20μm were individually injected into the dextran flows, demonstrating that dextran solutions at high concentration separated colloidal particles. Starch granules were separated by size using a dextran solution flow (250g/L). Thus, we expect to obtain efficient separation of colloidal particles in foods using highly concentrated dextran solutions. PMID:27112856

  3. Consistency of response to sumatriptan/naproxen sodium in a randomized placebo-controlled, cross-over study for the acute treatment of migraine in adolescence.

    PubMed

    Winner, Paul; Linder, Steven; Hershey, Andrew D

    2015-04-01

    A multi-centered, randomized, placebo-controlled, early intervention, cross-over study was conducted to evaluate the consistency of response of sumatriptan/naproxen sodium 85/500 mg (S/NS) over 4 attacks in the acute treatment of migraine in adolescents. Inclusion of subjects was dependent on their age of 12-17 years, frequency, and history of migraine headaches (1-8 per month) over the previous 6 months prior to screening and generally healthy males and females of non-childbearing potential that were not on excluded medications. Subjects were instructed to treat within 1 hour of pain onset, including when the pain was still mild. Subjects were randomized in a double-blind fashion using a computer-generated randomization list in which the study drug was prepared prior to study start, and subjects were allocated to a number in sequential order for each site. Each site was allocated number blocks in sets of 10 depending of the rate of enrollment. The objective of this study was to examine the efficacy of S/NS vs placebo in the primary end-points of pain-free response at 2 hours (2hPF), 24-hour sustained pain-free response (24hPF), and pain-free response at 2 hours with early intervention (2hPFE) calculated as percentage out of all attacks. In the study, 94 subjects treated 347 attacks in total: treating 277 with S/NS and 70 with placebo. Compared with placebo, S/NS produced higher 2hPF rates (S/NS 37%, placebo 18%; P < .004), and 2hPFE with rates (S/NS 32%, 18% placebo; P < .03). Compared with placebo, 24hPF rates were S/NS 86%, placebo 78%, P < .17, which were higher than placebo but not clinically significant. 2hPF was reported in at least 2 of the 3 migraines treated with S/NS in 40.4% of subjects. 24hPF was reported in at least 2 of the 3 migraine treated with S/NS in 86.2% subjects. Adverse reactions were generally low and comparable between S/NS and placebo.

  4. The interactions of fibrinogen and dextrans with erythrocytes

    PubMed Central

    Rampling, M.; Sirs, John A.

    1972-01-01

    1. The rate of packing of erythrocytes in whole blood, under a centrifugal field of 200 g, has been studied using an automatic recording centrifuge. 2. Reduction of the supernatant fibrinogen concentration, by repeatedly washing the cells, lowers the rate of packing and reduces the cell flexibility. 3. Resuspending the cells in their own plasma or in isotonic solutions containing fibrinogen restores their flexibility. 4. Rouleaux formation has been shown to have no effect on the rate of packing by comparison of blood diluted with plasma, isotonic NaCl or Ringer—Locke solutions. While the degree of rouleaux formation varied with the diluent used, the rate of packing and packed cell haematocrit were the same, for the same dilution. 5. Both formalin and dextran altered the degree of rouleaux formation and reduced erythrocyte flexibility. Dextran was found to act indirectly on the erythrocyte flexibility by reducing the plasma fibrinogen concentration. PMID:5046146

  5. Pharmacokinetic study of medicinal polymers: models based on dextrans

    SciTech Connect

    Kulakov, V.N.; Pimenova, G.N.; Matveev, V.A.; Sedov, V.V.; Vasil'ev, A.E.

    1986-09-01

    The authors study the pharmacokinetics of dextrans with various molecular masses modified by fluorescein isothiocyanate (FITC) using a radioisotope method. The radionuclide /sup 125/I was selectively bound to a FITC residue attached to the polysaccharide by electrochemical iodination under potentiostatic conditions. In the experiments, dextrans modified by FITC were labeled with /sup 125/I (DF-/sup 125/I) by electrochemical iodination. The separation of DF-/sup 125/I and FITC from ionic forms of the radionuclide not bound to the polymer was carried out. The properties of the samples obtained are presented. The radioactivity accumulated in the rate organs and urine studied are shown. The features of DF-/sup 125/I behavior in the blood and liver are examined.

  6. Sodium Test

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Sodium Share this page: Was this page helpful? Also known as: Na Formal name: Sodium Related tests: Chloride , Bicarbonate , Potassium , Electrolytes , Osmolality , Basic ...

  7. Initial studies of hypoxic radioprotection by deoxygenated dextran-hemoglobin

    SciTech Connect

    Hill, R.P.; Porter, L.S.; Ives, S.A.; Wong, J.T.F.

    1984-03-01

    Initial studies were performed to examine the potential of perfused dextran-hemoglobin to protect pig skin or mouse bone marrow cells against radiation damage. Some protection was indicated in both systems. In the pig skin a protection factor of 1.5 was observed for moist desquamation, and 2.0 for necrosis. These results suggest the possibility of using blood substitutes to induce tissue hypoxia for therapeutic purposes.

  8. Emulsifying properties of biodegradable polylactide-grafted dextran copolymers.

    PubMed

    Raynaud, J; Choquenet, B; Marie, E; Dellacherie, E; Nouvel, C; Six, J-L; Durand, A

    2008-03-01

    Amphiphilic glycopolymers, polylactide-grafted dextran copolymers (Dex-g-PLA), were synthesized with a well-controlled architecture obtained through a three-step procedure: partial silylation of the dextran hydroxyl groups, ring-opening polymerization of D,L-lactide initiated from remaining hydroxyl groups, silylether deprotection under very mild conditions. Depending on their proportion in polylactide (PLA), these copolymers exhibited solubility either in water or in organic solvents. The emulsifying properties of these glycopolymers were studied: depending on their PLA-to-dextran ratio, they were able to stabilize either direct or inverse emulsions. Droplet size was related to the amount of amphiphilic copolymer in the continuous phase. The aging mechanism of both direct and inverse emulsions was shown to be Ostwald ripening in the first weeks following preparation. Finally inverse miniemulsion copolymerization of acrylamide and N, N'-methylenebisacrylamide was performed in the presence of an amphiphilic Dex-g-PLA stabilizer. Polyacrylamide hydrogel nanoparticles were prepared in that way. PMID:18271550

  9. Ocular injectable formulation assessment for oxidized dextran-based hydrogels.

    PubMed

    Maia, João; Ribeiro, Maximiano P; Ventura, Carla; Carvalho, Rui A; Correia, Ilídio J; Gil, Maria H

    2009-07-01

    Initiator-free injectable hydrogels are very interesting for drug and/or cell delivery applications, since they can be administered in a minimally invasive way, and avoid the use of potentially harmful chemical initiators. In the current work, oxidized dextran crosslinked with adipic acid dihydrazide hydrogels were further characterized and tuned to produce formulations, with the aim of producing an injectable formulation for the possible treatment of posterior eye diseases. The gelation rate and the hydrogel dissolution profile were shown to be dependent on the balance between the degree of dextran oxidation, and the concentration of both components. For the in vitro studies, rabbit corneal endothelial cells were seeded on the hydrogels to assess cytotoxicity. Hydrogels prepared with low oxidized dextrans were able to promote cell adhesion and proliferation to confluence in just 24h, while more highly oxidized samples promoted cell adhesion and proliferation, but without achieving confluence. Cell viability studies were performed using MTS assays to verify the non-cytotoxicity of hydrogels and their degradation byproducts, rendering these formulations attractive for further in vivo studies. PMID:19286432

  10. Fucoidan Extracts Ameliorate Acute Colitis.

    PubMed

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

    2015-01-01

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

  11. Prolonging the circulatory retention of SPIONs using dextran sulfate: in vivo tracking achieved by functionalisation with near-infrared dyes.

    PubMed

    Abdollah, Maha R A; Kalber, Tammy; Tolner, Berend; Southern, Paul; Bear, Joseph C; Robson, Mathew; Pedley, R Barbara; Parkin, Ivan P; Pankhurst, Quentin A; Mulholland, Paul; Chester, Kerry

    2014-01-01

    The rapid reticuloendothelial system (RES) mediated clearance of superparamagnetic iron oxide nanoparticles (SPIONs) from circulation is considered a major limitation of their clinical utility. We aimed to address this by using dextran sulfate 500 (DSO4 500), a Kupffer cell blocking agent, to prolong SPIONs circulatory time. Blood concentrations of SPIONs are difficult to quantify due to the presence of haemoglobin. We therefore developed methods to functionalise SPIONs with near-infrared (NIR) dyes in order to trace their biodistribution. Two SPIONs were investigated: Nanomag®-D-spio-NH(2) and Ferucarbotran. Nanomag®-D-spio-NH(2) was functionalised using NHS (N-hydroxysuccinimide) ester NIR dye and Ferucarbotran was labelled using periodate oxidation followed by reductive amination or a combination of EDC (ethyl(dimethylaminopropyl) carbodiimide )/NHS and click chemistries. Stability after conjugation was confirmed by dynamic light scattering (DLS), superconducting quantum interference device (SQUID) and transmission electron microscopy (TEM). In vivo experiments with the functionalised SPIONs showed a significant improvement in SPIONs blood concentrations in mice pre-treated with dextran sulfate sodium salt 500 (DSO4 500).

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

    PubMed

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

    2014-11-01

    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.

  13. A study of dextran production from maltodextrin by cell suspensions of Gluconobacter oxydans NCIB 4943.

    PubMed

    Mountzouris, K C; Gilmour, S G; Jay, A J; Rastall, R A

    1999-10-01

    This study investigated dextran synthesis from a commercial maltodextrin substrate using cell suspensions of G. oxydans NCIB 4943 as catalysts. Experiments were arranged according to a central composite statistical design. The effects of substrate concentration (10-100 g l-1), cell concentration (0.32-32.0 g wet weight l-1), time of reaction (8-48 h) and pH (3.5-5.5), each at three levels, on dextran yield and dextran molecular weight (MW), were investigated. Response surface methodology was used to assess factor interactions, and empirical models describing the two responses were fitted. Most of the variance in dextran yield could be explained by the fitted model (R2 = 0.96). Dextran yield ranged from 1.21 to 41.69%. The presence of significant negative quadratic effects of cell concentration and time indicated that dextran yield reached a plateau and thus, optimum levels of cell concentration and time could be identified to maximize dextran yield. Dextran MW ranged from 6.6 to 38 kDa and was characterized by the significant interactions of reaction time with substrate concentration and cell concentration. The model, however, could account for only 60% of the variance in dextran MW. Possible reasons for this are discussed.

  14. Cellular interactions of lauric acid and dextran-coated magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Pradhan, Pallab; Giri, Jyotsnendu; Banerjee, Rinti; Bellare, Jayesh; Bahadur, Dhirendra

    2007-04-01

    In vitro cytocompatibility and cellular interactions of lauric acid and dextran-coated magnetite nanoparticles were evaluated with two different cell lines (mouse fibroblast and human cervical carcinoma). Lauric acid-coated magnetite nanoparticles were less cytocompatible than dextran-coated magnetite nanoparticles and cellular uptake of lauric acid-coated magnetic nanoparticles was more than that of dextran-coated magnetite nanoparticles. Lesser cytocompatibility and higher uptake of lauric acid-coated magnetite nanoparticles as compared to dextran-coated magnetic nanoparticles may be due to different cellular interactions by coating material. Thus, coating plays an important role in modulation of biocompatibility and cellular interaction of magnetic nanoparticles.

  15. Comparative study of the ocular efficacy and safety of diclofenac sodium (0.1%) ophthalmic solution with that of ketorolac tromethamine (0.5%) ophthalmic solution in patients with acute seasonal allergic conjunctivitis

    PubMed Central

    Dehar, Navdeep; Gupta, Anita; Singh, Gursatinder

    2012-01-01

    Background: Seasonal allergic conjunctivitis (SAC) is the most common and most prevalent of allergic disorders which afflict the ocular surface. Of the several treatments available, ophthalmic non-steroidal anti-inflammatory drugs, are generally very safe and tolerable. Aim: The aim of this study is to compare the ocular efficacy and safety of diclofenac sodium (0.1%) ophthalmic solution with that of ketorolac tromethamine (0.5%) ophthalmic solution in patients with acute SAC. Materials and Methods: Sixty patients with signs and symptoms of SAC were evaluated in an open, randomized, parallel group study. The principle symptoms (ocular itching, burning, discharge, photophobia) and signs (ocular inflammation, lid edema, chemosis, conjunctival mucous, keratitis) were evaluated. Study Design: Patients were randomized into two groups of 30 each. Patients in group A received one drop of diclofenac sodium 0.1% and patients in group B received ketorolac tromethamine 0.5% in both the eyes four times a day for fourteen days. Evaluations were performed at day 0, 3, 7 and 14 of the therapy. At each visit, the signs and symptoms were rated using a scale from 0-3 (mild-1, moderate-2 and severe-3). Results: Significant clinical and statistical reductions in signs and symptoms from baseline were observed in both groups. Diclofenac sodium 0.1% was superior to ketorolac tromethamine 0.5% in reducing ocular itching (P < 0.05) and ocular inflammation (P < 0.05), at the final examination. Conclusion: Diclofenac sodium showed statistically significant better results at day 3 and 7 compared to ketorolac. PMID:23776804

  16. Comparison of the relative propensities of isoamyl nitrite and sodium nitrite to ameliorate acute cyanide poisoning in mice and a novel antidotal effect arising from anesthetics.

    PubMed

    Cambal, Leah K; Weitz, Andrew C; Li, Hui-Hua; Zhang, Yang; Zheng, Xi; Pearce, Linda L; Peterson, Jim

    2013-05-20

    Isoamyl nitrite has previously been considered acceptable as an inhaled cyanide antidote; therefore, the antidotal utility of this organic nitrite compared with sodium nitrite was investigated. To facilitate a quantitative comparison, doses of both sodium nitrite and isoamyl nitrite were given intraperitoneally in equimolar amounts to sublethally cyanide-challenged mice. Righting recovery from the knockdown state was clearly compromised in the isoamyl nitrite-treated animals, the effect being attributable to the toxicity of the isoamyl alchol produced during hydrolysis of the isoamyl nitrite to release nitrite anion. Subsequently, inhaled aqueous sodium nitrite aerosol was demonstrated to ameliorate sublethal cyanide toxicity, when provided to mice after the toxic dose, by the more rapid recovery of righting ability compared to that of the control animals given only the toxicant. Aerosolized sodium nitrite has thus been shown by these experiments to have promise as a better alternative to organic nitrites for development as an inhaled cyanide antidote. The inhaled sodium nitrite led to the production of NO in the bloodstream as determined by the appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin. The aerosol delivery was performed in an unmetered inhalation chamber, and in this study, no attempt was made to optimize the procedure. It is argued that administration of an effective inhaled aqueous sodium nitrite dose in humans is possible, though just beyond the capability of current individual metered-dose inhaler designs, such as those used for asthma. Finally, working at slightly greater than LD50 NaCN doses, it was fortuitously discovered that (i) anesthesia leads to significantly prolonged survival compared to that of unanesthetized animals and that (ii) the antidotal activity of nitrite anion was completely abolished under anesthesia. Plausible explanations for these effects in mice and their practical consequences in relation to

  17. Comparison of the relative propensities of isoamyl nitrite and sodium nitrite to ameliorate acute cyanide poisoning in mice and a novel antidotal effect arising from anesthetics.

    PubMed

    Cambal, Leah K; Weitz, Andrew C; Li, Hui-Hua; Zhang, Yang; Zheng, Xi; Pearce, Linda L; Peterson, Jim

    2013-05-20

    Isoamyl nitrite has previously been considered acceptable as an inhaled cyanide antidote; therefore, the antidotal utility of this organic nitrite compared with sodium nitrite was investigated. To facilitate a quantitative comparison, doses of both sodium nitrite and isoamyl nitrite were given intraperitoneally in equimolar amounts to sublethally cyanide-challenged mice. Righting recovery from the knockdown state was clearly compromised in the isoamyl nitrite-treated animals, the effect being attributable to the toxicity of the isoamyl alchol produced during hydrolysis of the isoamyl nitrite to release nitrite anion. Subsequently, inhaled aqueous sodium nitrite aerosol was demonstrated to ameliorate sublethal cyanide toxicity, when provided to mice after the toxic dose, by the more rapid recovery of righting ability compared to that of the control animals given only the toxicant. Aerosolized sodium nitrite has thus been shown by these experiments to have promise as a better alternative to organic nitrites for development as an inhaled cyanide antidote. The inhaled sodium nitrite led to the production of NO in the bloodstream as determined by the appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin. The aerosol delivery was performed in an unmetered inhalation chamber, and in this study, no attempt was made to optimize the procedure. It is argued that administration of an effective inhaled aqueous sodium nitrite dose in humans is possible, though just beyond the capability of current individual metered-dose inhaler designs, such as those used for asthma. Finally, working at slightly greater than LD50 NaCN doses, it was fortuitously discovered that (i) anesthesia leads to significantly prolonged survival compared to that of unanesthetized animals and that (ii) the antidotal activity of nitrite anion was completely abolished under anesthesia. Plausible explanations for these effects in mice and their practical consequences in relation to

  18. IL-33 Aggravates DSS-Induced Acute Colitis in Mouse Colon Lamina Propria by Enhancing Th2 Cell Responses.

    PubMed

    Zhu, Junfeng; Yang, Fangli; Sang, Lixuan; Zhai, Jingbo; Zhang, Xiaoqing; Yue, Dan; Li, Shengjun; Li, Yan; Lu, Changlong; Sun, Xun

    2015-01-01

    Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL-33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)γ and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4(+)T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis.

  19. Effect of saccharated ferric oxide and iron dextran on the metabolism of phosphorus in rats.

    PubMed

    Sanai, Toru; Oochi, Nobuaki; Okada, Mitsuo; Imamura, Kenzaburo; Okuda, Seiya; Iida, Mitsuo

    2005-07-01

    As a means of investigating the physiologic damage to and histologic deterioration of the kidney caused by saccharated ferric oxide (SFO) and iron dextran (ID), we administered these substances intraperitoneally to rats. The rats were divided into 3 groups. Group 1 rats ( n = 7) were given SFO, 28 mg/kg for 9 days and 20 mg/kg for 19 days. Group 2 rats ( n = 5) were given ID, 28 mg/kg for 9 days and 20 mg/kg for 19 days. Group 3 rats (control, n = 9) were given normal saline solution. After 28 days, serum calcium, total protein, and albumin concentrations were significantly lower in the SFO group than in the ID group. Serum phosphorus concentrations were significantly lower in the SFO group than in the control group. Serum iron concentrations were significantly higher in the ID group than in the SFO group or the control, and the fractional excretion of sodium was significantly lower in the ID group than in the control group. The percent tubular reabsorption of phosphorus was significantly greater in the ID group than in the SFO group or the control group, and the theoretical threshold concentration of phosphorus was also significantly lower in the SFO group than in the ID or the control group. Histologic examination of the kidney after treatment revealed neither iron in the tubules nor any structural damage to the tubules. ID was not found to induce hypophosphatemia, whereas SFO did. We believe that the cause of such hypophosphatemia is impaired tubular reabsorption.

  20. Boehmeria nivea Attenuates the Development of Dextran Sulfate Sodium-Induced Experimental Colitis

    PubMed Central

    Shin, Eun Ju; Sung, Mi Jeong; Yang, Hye Jeong; Kim, Myung Sunny; Hwang, Jin-Taek

    2014-01-01

    We examined the therapeutic effect of an ethanol extract derived from Boehmeria nivea (Linn.) Gaudich in a mouse model of experimental colitis. Treatment with 70% ethanol extract derived from B. nivea (EBN) at a dose of 100, 200, or 500 mg/(kg·d) improved colon shortening, body weight, the disease activity index (DAI), and histopathological score of DSS-induced colitis mice. DSS significantly increased the levels of cyclooxygenase-(COX-) 2 in colon tissue relative to that of the untreated control group. EBN administered at 100, 200, or 500 mg/(kg·d) reduced COX-2 levels in the DSS-treated mice. In addition, EBN decreased the DSS-induced secretion of the inflammatory cytokine interleukin-6 (IL-6) and chemokine monocyte chemotactic protein-1 (MCP-1). Taken together, these data suggest that B. nivea extract is effective in preventing colitis. PMID:25045208

  1. Treatment of dextran sodium sulfate-induced experimental colitis by adoptive transfer of peritoneal cells

    PubMed Central

    Liu, Ting; Ren, Jun; Wang, Wei; Wei, Xia-wei; Shen, Guo-bo; Liu, Yan-tong; Luo, Min; Xu, Guang-chao; Shao, Bin; Deng, Sen-yi; He, Zhi-yao; Liang, Xiao; Liu, Yu; Wen, Yan-Zhu; Xiang, Rong; Yang, Li; Deng, Hong-xin; Wei, Yu-quan

    2015-01-01

    The adoptive transfer of the natural regulatory B cells and macrophages should be a useful treatment for inflammation and autoimmune disease. However, it is usually difficult to isolate these cells from the tissues and expand them. Here, we investigated the feasibility of adoptively transferring peritoneal cells (PCs) as a treatment for DSS-induced colitis. We found that peritoneal cavity can provide an easily accessible site for harvesting enough number of PCs, namely, two-dose PCs for the treatment from a mouse in one operation. Adoptive therapy of these cells from healthy mice or those with disease is effectively in reducing the disease activity score. The natural B cells and macrophages of the infused PCs can selectively migrate to lesion sites and regulate the expression of Stat3, NF−κB, Smad3 and Smad7. Additionally, PCs exert dual activity of IL-10 and TGF-β secreted spontaneously by both peritoneal B cells and macrophages, which in turn enhance the induction of regulatory B cells and Macrophages in microenvironment of inflammation. Moreover, PCs can re-establish immunological tolerance in the OVA-immunized mice. Thus, our findings provide a new strategy for colitis therapy and could be of importance in additional exploration of other inflammation and autoimmune diseases therapy. PMID:26565726

  2. Protective Effect of Amphipterygium adstringens Extract on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice.

    PubMed

    Rodriguez-Canales, Mario; Jimenez-Rivas, Ruben; Canales-Martinez, Maria Margarita; Garcia-Lopez, Ana Judith; Rivera-Yañez, Nelly; Nieto-Yañez, Oscar; Ledesma-Soto, Yadira; Sanchez-Torres, Luvia Enid; Rodriguez-Sosa, Miriam; Terrazas, Luis Ignacio; Rodriguez-Monroy, Marco Aurelio

    2016-01-01

    Amphipterygium adstringens is an endemic species in Mexico commonly known as "cuachalalate." Healers to treat gastritis, gastric ulcers, and gastrointestinal cancer have traditionally used the bark. We investigated the effects of alcoholic extract of A. adstringens (AaEE) in DSS-induced colitis in mice. The protective effect of AaEE was determined at 200 mg/kg by oral gavage for 10 days. We determine the effect of AaEE on clinical features (disease activity index), antioxidants, anti-inflammatory, and immunomodulatory activities in relation to the activity of SOD, CAT, and GPx, levels of proinflammatory cytokines, and changes both macroscopic and microscopic of the colonic mucosa. AaEE significantly reduced the inflammation of colon and significantly increased SOD and GPx activities. AaEE also significantly decreased TNF-α, IFN-γ, and IL-1β cytokine levels compared to DSS-treated mice and reduced both infiltration of inflammatory cells and the mucosal damage in colon. The results suggested the protective potential of AaEE in DSS-induced colitis and this might be attributed to its phytochemicals compounds that have been found to induce a wide spectrum of activities such as reduction in oxidative stress, suppression of inflammation, modulating numerous signal transduction pathways, and induction of apoptosis. The findings of this study suggest that AaEE has substantial potential for the treatment of inflammatory colitis. PMID:27635116

  3. Protective Effect of Amphipterygium adstringens Extract on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice

    PubMed Central

    Rodriguez-Canales, Mario; Jimenez-Rivas, Ruben; Canales-Martinez, Maria Margarita; Garcia-Lopez, Ana Judith; Rivera-Yañez, Nelly; Nieto-Yañez, Oscar; Ledesma-Soto, Yadira; Sanchez-Torres, Luvia Enid; Rodriguez-Sosa, Miriam; Terrazas, Luis Ignacio

    2016-01-01

    Amphipterygium adstringens is an endemic species in Mexico commonly known as “cuachalalate.” Healers to treat gastritis, gastric ulcers, and gastrointestinal cancer have traditionally used the bark. We investigated the effects of alcoholic extract of A. adstringens (AaEE) in DSS-induced colitis in mice. The protective effect of AaEE was determined at 200 mg/kg by oral gavage for 10 days. We determine the effect of AaEE on clinical features (disease activity index), antioxidants, anti-inflammatory, and immunomodulatory activities in relation to the activity of SOD, CAT, and GPx, levels of proinflammatory cytokines, and changes both macroscopic and microscopic of the colonic mucosa. AaEE significantly reduced the inflammation of colon and significantly increased SOD and GPx activities. AaEE also significantly decreased TNF-α, IFN-γ, and IL-1β cytokine levels compared to DSS-treated mice and reduced both infiltration of inflammatory cells and the mucosal damage in colon. The results suggested the protective potential of AaEE in DSS-induced colitis and this might be attributed to its phytochemicals compounds that have been found to induce a wide spectrum of activities such as reduction in oxidative stress, suppression of inflammation, modulating numerous signal transduction pathways, and induction of apoptosis. The findings of this study suggest that AaEE has substantial potential for the treatment of inflammatory colitis. PMID:27635116

  4. Oat β-glucan ameliorates dextran sulfate sodium (DSS)-induced ulcerative colitis in mice.

    PubMed

    Liu, Bo; Lin, Qinlu; Yang, Tao; Zeng, Linna; Shi, Limin; Chen, Yaya; Luo, Feijun

    2015-11-01

    Ulcerative colitis is a major inflammatory bowel disease (IBD), characterized by inflammation within the gastrointestinal tract through chronic or relapsing immune system activation. The aim of this study is to investigate the potential protective effect of oat β-glucan (βG) against colitis induced by DSS in mice. Eighty mice were randomly divided into the control group (no DSS, no βG), DSS group (DSS only), DSS + L-βG group (DSS plus 500 mg per kg βG), and DSS + H-βG group (DSS plus 1000 mg per kg βG). Compared with the DSS group, administration of βG significantly reduced clinical symptoms with less weight loss, diarrhea and shortening of the colon, the severity of colitis was significantly inhibited as evidenced by the reduced disease activity index (DAI) and degree of histological damage in colon. Moreover, treatment with βG not only decreased myeloperoxidase activity (MPO), and nitric oxide (NO) and malondialdehyde (MDA) levels, but also inhibited mRNA and protein expression of pro-inflammatory factors such as TNF-α, IL-1β, IL-6 and iNOS. This suggests that oat βG in diet might exhibit an anti-inflammatory function against colitis through inhibition of expression of pro-inflammatory factors. PMID:26292622

  5. Protective Effect of Amphipterygium adstringens Extract on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice

    PubMed Central

    Rodriguez-Canales, Mario; Jimenez-Rivas, Ruben; Canales-Martinez, Maria Margarita; Garcia-Lopez, Ana Judith; Rivera-Yañez, Nelly; Nieto-Yañez, Oscar; Ledesma-Soto, Yadira; Sanchez-Torres, Luvia Enid; Rodriguez-Sosa, Miriam; Terrazas, Luis Ignacio

    2016-01-01

    Amphipterygium adstringens is an endemic species in Mexico commonly known as “cuachalalate.” Healers to treat gastritis, gastric ulcers, and gastrointestinal cancer have traditionally used the bark. We investigated the effects of alcoholic extract of A. adstringens (AaEE) in DSS-induced colitis in mice. The protective effect of AaEE was determined at 200 mg/kg by oral gavage for 10 days. We determine the effect of AaEE on clinical features (disease activity index), antioxidants, anti-inflammatory, and immunomodulatory activities in relation to the activity of SOD, CAT, and GPx, levels of proinflammatory cytokines, and changes both macroscopic and microscopic of the colonic mucosa. AaEE significantly reduced the inflammation of colon and significantly increased SOD and GPx activities. AaEE also significantly decreased TNF-α, IFN-γ, and IL-1β cytokine levels compared to DSS-treated mice and reduced both infiltration of inflammatory cells and the mucosal damage in colon. The results suggested the protective potential of AaEE in DSS-induced colitis and this might be attributed to its phytochemicals compounds that have been found to induce a wide spectrum of activities such as reduction in oxidative stress, suppression of inflammation, modulating numerous signal transduction pathways, and induction of apoptosis. The findings of this study suggest that AaEE has substantial potential for the treatment of inflammatory colitis.

  6. Tanshinone IIA ameliorates dextran sulfate sodium-induced inflammatory bowel disease via the pregnane X receptor

    PubMed Central

    Zhang, Xianxie; Wang, Yuguang; Ma, Zengchun; Liang, Qiande; Tang, Xianglin; Hu, Donghua; Tan, Hongling; Xiao, Chengrong; Gao, Yue

    2015-01-01

    Tanshinone IIA (Tan IIA) (C19H18O3) is one of the major active lipophilic components in a conventional Chinese medicine called danshen, and it has long been used in the People’s Republic of China and other neighboring countries to treat patients suffering from inflammatory bowel disease (IBD). Previous experiments by many teams determined which mechanism of Tan IIA is relevant to the treatment of IBD associated with inflammation and the pregnane X receptor (PXR). The current study demonstrated that Tan IIA is an efficacious PXR agonist and its ability to induce CYP3A4 mRNA and protein expression was mediated by the transactivation of PXR, a known target of abrogating inflammation in IBD. Clinical symptoms in mice and histological assessment data suggested that administration of Tan IIA in mice demonstrated significant protection and showed that in DSS-induced IBD it acts in a concentration-dependent manner. PXR-silenced mice treated with Tan IIA demonstrated low protection against DSS-induced mouse IBD and exacerbated the severity of IBD compared with wild-type mice; PXR-silenced mice demonstrated the necessity for PXR in Tan IIA-mediated upregulation of xenobiotic metabolism genes. The IBD treatment effects of Tan IIA are partially due to PXR-mediated upregulation of xenobiotic metabolism and downregulation of inflammatory mediators. The novel findings reported here may contribute to the effective utilization of Tan IIA and its derivatives as a PXR ligand in the treatment of human IBD. This suggests that Tan IIA may have considerable clinical utility. PMID:26674743

  7. Oat β-glucan ameliorates dextran sulfate sodium (DSS)-induced ulcerative colitis in mice.

    PubMed

    Liu, Bo; Lin, Qinlu; Yang, Tao; Zeng, Linna; Shi, Limin; Chen, Yaya; Luo, Feijun

    2015-11-01

    Ulcerative colitis is a major inflammatory bowel disease (IBD), characterized by inflammation within the gastrointestinal tract through chronic or relapsing immune system activation. The aim of this study is to investigate the potential protective effect of oat β-glucan (βG) against colitis induced by DSS in mice. Eighty mice were randomly divided into the control group (no DSS, no βG), DSS group (DSS only), DSS + L-βG group (DSS plus 500 mg per kg βG), and DSS + H-βG group (DSS plus 1000 mg per kg βG). Compared with the DSS group, administration of βG significantly reduced clinical symptoms with less weight loss, diarrhea and shortening of the colon, the severity of colitis was significantly inhibited as evidenced by the reduced disease activity index (DAI) and degree of histological damage in colon. Moreover, treatment with βG not only decreased myeloperoxidase activity (MPO), and nitric oxide (NO) and malondialdehyde (MDA) levels, but also inhibited mRNA and protein expression of pro-inflammatory factors such as TNF-α, IL-1β, IL-6 and iNOS. This suggests that oat βG in diet might exhibit an anti-inflammatory function against colitis through inhibition of expression of pro-inflammatory factors.

  8. 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.

  9. Rapid monoclonal antibody adsorption on dextran-grafted agarose media for ion-exchange chromatography.

    PubMed

    Tao, Yinying; Carta, Giorgio

    2008-11-21

    The binding capacity and adsorption kinetics of a monoclonal antibody (mAb) are measured for experimental cation exchangers obtained by grafting dextran polymers to agarose beads and compared with measurements for two commercial agarose-based cation exchangers with and without dextran grafts. Introduction of charged dextran polymers results in enhanced adsorption kinetics despite a dramatic reduction of the accessible pore size as determined by inverse size-exclusion chromatography. Incorporation of neutral dextran polymers in a charged agarose bead results instead in substantially lower binding capacities. The effective pore diffusivities obtained from batch uptake curves increase substantially as the protein concentration is reduced for the resins containing charged dextran grafts, but are much less dependent on protein concentration for the resins with no dextran or uncharged dextran grafts. The batch uptake results are corroborated by microscopic observations of transient adsorption in individual particles. In all cases studied, the adsorption kinetics is characterized by a sharp adsorption front consistent with a shell-progressive, diffusion limited mechanism. Greatly enhanced transport rates are obtained with an experimental resin containing charged dextran grafts with effective pore diffusivities that are 1-9 times larger than the free solution diffusivity and adsorption capacity approaching 300 mg/cm3 of particle volume.

  10. In situ production and analysis of Weissella confusa dextran in wheat sourdough.

    PubMed

    Katina, Kati; Maina, Ndegwa Henry; Juvonen, Riikka; Flander, Laura; Johansson, Liisa; Virkki, Liisa; Tenkanen, Maija; Laitila, Arja

    2009-10-01

    Several lactic acid bacteria belonging to the genera Leuconostoc, Lactobacillus, and Weissella have been introduced to wheat sourdough baking for in situ production of exopolysaccharides. This is considered a novel method for improving the shelf-life, volume and nutritional value of bread without additives. However, in situ production of exopolysaccharides during sourdough fermentation is challenged by simultaneous acidification due to metabolic activities of the bacteria, which may significantly diminish the positive technological impact of exopolysaccharides. In this study, the growth, activity and in situ production of dextran by Weissella confusa VTT E-90392 in wheat sourdoughs were investigated. Furthermore, the influence of dextran-enriched sourdoughs, at the addition level of 43%, on the subsequent bread quality was established. W. confusa efficiently produced dextran from the added sucrose in wheat sourdough without strong acid production. A new specific enzyme-assisted method for in situ analysis of dextran in sourdoughs was developed. With this method, we could for the first time proof significant (11-16 g/kg DW) production of polymeric dextran in sourdoughs. Concomitant formation of shorter isomaltooligosaccharides by W. confusa was also detected. The produced dextran significantly increased the viscosity of the sourdoughs. Application of dextran-enriched sourdoughs in bread baking provided mildly acidic wheat bread with improved volume (up to 10%) and crumb softness (25-40%) during 6 days of storage. Hence, W. confusa is a promising new strain for efficient in situ production of dextrans and isomaltooligosaccharides in sourdoughs without strong acidification.

  11. 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.

  12. 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

    2014-11-01

    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.

  13. 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. PMID:26927936

  14. Terpene and dextran renewable resources for the synthesis of amphiphilic biopolymers.

    PubMed

    Alvès, Marie-Hélène; Sfeir, Huda; Tranchant, Jean-François; Gombart, Emilie; Sagorin, Gilles; Caillol, Sylvain; Billon, Laurent; Save, Maud

    2014-01-13

    The present work shows the synthesis of amphiphilic polymers based on the hydrophilic dextran and the hydrophobic terpenes as renewable resources. The first step concerns the synthesis of functional terpene molecules by thiol-ene addition chemistry involving amino or carboxylic acid thiols and dihydromyrcenol terpene. The terpene-modified polysaccharides were subsequently synthesized by coupling the functional terpenes with dextran. A reductive amination step produced terpene end-modified dextran with 94% of functionalization, while the esterification step produced three terpene-grafted dextrans with a number of terpene units per dextran of 1, 5, and 10. The amphiphilic renewable grafted polymers were tested as emulsifiers for the stabilization of liquid miniemulsion of terpene droplets dispersed in an aqueous phase. The average hydrodynamic diameter of the stable droplets was observed at about 330 nm.

  15. Biomedical properties and preparation of iron oxide-dextran nanostructures by MAPLE technique

    PubMed Central

    2012-01-01

    Background In this work the chemical structure of dextran-iron oxide thin films was reported. The films were obtained by MAPLE technique from composite targets containing 10 wt. % dextran with 1 and 5 wt.% iron oxide nanoparticles (IONPs). The IONPs were synthesized by co-precipitation method. A KrF* excimer laser source (λ = 248 nm, τFWHM≅25 ns, ν = 10 Hz) was used for the growth of the hybrid, iron oxide NPs-dextran thin films. Results Dextran coated iron oxide nanoparticles thin films were indexed into the spinel cubic lattice with a lattice parameter of 8.36 Å. The particle sized calculated was estimated at around 7.7 nm. The XPS shows that the binding energy of the Fe 2p3/2 of two thin films of dextran coated iron oxide is consistent with Fe3+ oxides. The atomic percentage of the C, O and Fe are 66.71, 32.76 and 0.53 for the films deposited from composite targets containing 1 wt.% maghemite and 64.36, 33.92 and 1.72 respectively for the films deposited from composite targets containing 5 wt.% maghemite. In the case of cells cultivated on dextran coated 5% maghemite γ-Fe2O3, the number of cells and the level of F-actin were lower compared to the other two types of thin films and control. Conclusions The dextran-iron oxide continuous thin films obtained by MAPLE technique from composite targets containing 10 wt.% dextran as well as 1 and 5 wt.% iron oxide nanoparticles synthesized by co-precipitation method presented granular surface morphology. Our data proved a good viability of Hep G2 cells grown on dextran coated maghemite thin films. Also, no changes in cells morphology were noticed under phase contrast microscopy. The data strongly suggest the potential use of iron oxide-dextran nanocomposites as a potential marker for biomedical applications. PMID:22410001

  16. Sodium Oxybate

    MedlinePlus

    ... used to prevent attacks of cataplexy (episodes of muscle weakness that begin suddenly and last for a ... of your body that you cannot control, sweating, muscle cramps, and fast heartbeat.Sodium oxybate may help ...

  17. EUGLYCEMIC DIABETIC KETOACIDOSIS AND SEVERE ACUTE KIDNEY INJURY SECONDARY TO OFF LABEL USE OF SODIUM GLUCOSE COTRANSPORTER-2 INHIBITOR IN A TYPE-1 DIABETIC PATIENT.

    PubMed

    Tahir, Hassan; Wani, Adil; Daruwalla, Vistasp; Daboul, Nour; Sagi, Jahnavi

    2015-01-01

    Sodium glucose Cotransporter-2 (SGLT2) inhibitors are a new class of drug approved for the treatment of type-2 diabetes; however they are also increasingly used off label in type-1 diabetic patients. SGLT2 Inhibitors work by increasing glucose excretion in urine. Euglycemic diabetic ketoacidosis (DKA) is potentially life threatening side effect as patients have normal glucose and minimal symptoms thus delaying diagnosis and treatment. Our case report highlights the risk of using SGLT2 inhibitors in type-1 diabetes and also supports the need for long term studies to define clear efficacy and complications of SGLT 2 inhibitors in both type-1 and type 2 diabetes mellitis. PMID:27004352

  18. Chondrogenesis in injectable enzymatically crosslinked heparin/dextran hydrogels.

    PubMed

    Jin, Rong; Moreira Teixeira, Liliana S; Dijkstra, Pieter J; van Blitterswijk, Clemens A; Karperien, Marcel; Feijen, Jan

    2011-05-30

    In this study, injectable hydrogels were prepared by horseradish peroxidase-mediated co-crosslinking of dextran-tyramine (Dex-TA) and heparin-tyramine (Hep-TA) conjugates and used as scaffolds for cartilage tissue engineering. The swelling and mechanical properties of these hydrogels can be easily controlled by the Dex-TA/Hep-TA weight ratio. When chondrocytes were incorporated in these gels, cell viability and proliferation were highest for gels with a 50/50 weight ratio of Dex-TA/Hep-TA. Moreover, these hydrogels induced an enhanced production of chondroitin sulfate and a more abundant presence of collagen as compared to Dex-TA hydrogels. The results indicate that injectable Dex-TA/Hep-TA hydrogels are promising scaffolds for cartilage regeneration. PMID:21291927

  19. 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

  20. Sucrose crystal growth in the presence of dextran of different molecular weights

    NASA Astrophysics Data System (ADS)

    Khaddour, Issam; Ferreira, António; Bento, Luís; Rocha, Fernando

    2012-09-01

    The effects of variable concentrations of different molecular weight fractions of dextran on the interfacial free energies and the kinetic coefficients of the overall linear growth rates of the sucrose crystal were evaluated at 40 and 50 °C. Dextrans-reducing effects on the interfacial free energy increased the overall linear growth rates of sucrose at 40 °C. Further, dextrans-reducing effects of the growth kinetic coefficients resulted in lower growth rates of the sucrose crystals at 50 °C. Impurity effectiveness factor, differential heat of adsorption and Langmuir isotherm constant were determined, for the used dextrans, at 50 °C and relative supersaturation of 0.161. The dextran of molecular fraction of 2000 kilo Daltons (kDa) showed considerably high effectiveness factor in comparison with the dextrans of molecular fractions of 70 and 250 kDa. Role of dextran in retarding the advancement of the growth steps in the vicinity of its incorporation on the face (100) of the sucrose crystal is pointed out using AFM technique.

  1. 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

  2. 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.

  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

    2016-01-01

    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

  4. Method for chromatographic analysis of whey protein-dextran glycation products.

    PubMed

    Allelein, Susann; Arunkumar, Abhiram; Etzel, Mark R

    2012-12-28

    A chromatographic method for the analysis of whey protein isolate (WPI)-dextran glycates was developed in this work that is useful for quantification of sample purity and concentration, and as a sample-preparation method for subsequent analysis by gel electrophoresis (SDS-PAGE) and laser-light scattering. Glycation was by the Maillard reaction between WPI and dextran of 3 different sizes. Glycate fractions from each dextran were collected and analyzed by fluorescent and glycoprotein staining of gels, bicinchoinic acid protein assay, and static and dynamic laser light scattering. The weight-average molecular mass of the glycates was 27-34 kDa (from 3.5 kDa dextran), 32-39 kDa (from 10 kDa dextran), and 250-270 kDa (from 150 kDa dextran). The new method was used to characterize the kinetics of the glycation reaction, which followed a reversible pseudo first-order model. The kinetics of decomposition of the purified glycate by hydrolysis was also examined. The new method is rapid (25 min) and quantitative, and is the first chromatographic method for direct analysis of WPI-dextran glycation products. PMID:23182287

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

    PubMed

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

    2015-07-01

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

  6. An estimate of the enthalpic contribution to the interaction between dextran and albumin.

    PubMed Central

    Comper, W D; Laurent, T C

    1978-01-01

    It is demonstrated that exclusion phenomena appear to dominate the interaction of dextran with albumin in aqueous solution. The enthalpic contribution to the interaction coefficient describing dextran/albumin mixtures is small, although its determination was subject to considerable error. These results support the earlier assumptions of the type of interaction between the two polymers. The conclusions are primarily based on the interpretation of the temperature-dependence of the interaction coefficient, as measured by light-scattering in the temperature range 6--33 degrees C. Enthalpy of dilution measurements of dextran/albumin mixtures by microcalorimetry were in qualitative agreement with the light-scattering data. PMID:743220

  7. Kimchi Protects Against Azoxymethane/Dextran Sulfate Sodium–Induced Colorectal Carcinogenesis in Mice

    PubMed Central

    Kim, Hee-Young; Song, Jia-Le; Chang, Hee-Kyung; Kang, Soon-Ah

    2014-01-01

    Abstract The chemopreventive effects of different types and quantities of kimchi prepared with different subingredients, including commercial kimchi (CK), standardized kimchi (SK), cancer-preventive kimchi (CPK), and anticancer kimchi (ACK), on colorectal carcinogenesis in mice were evaluated. The development of colon cancer was induced in male BALB/c mice with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and subsequent treatment with 2% dextran sulfate sodium (DSS) in drinking water for 7 days for two cycles. After exposure to AOM and DSS, treatment with the methanolic extracts from different kimchis, particularly 1.89 g/kg of ACK, significantly increased colon length, decreased the ratio of colon weight/length, and resulted in the lowest number of tumors compared with the other kimchi-treated groups. Histological observation revealed that ACK was able to suppress AOM- and DSS-induced colonic mucosal damage and neoplasia. ACK also significantly decreased the mRNA levels of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) as well as the mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2). In addition, the mRNA and protein expression of p53 and p21 was elevated in colon tissues from the ACK-treated mice compared with the other kimchi-treated groups. Our results suggest that kimchi exerted a suppressive effect on AOM- and DSS-induced colorectal carcinogenesis in the BALB/c mice. The anticancer effects of ACK were particularly potent. Thus, it is possible that the health-promoting subingredients added to ACK might be used to prevent colon carcinogenesis in humans. PMID:25029638

  8. Dual chitosan/albumin-coated alginate/dextran sulfate nanoparticles for enhanced oral delivery of insulin.

    PubMed

    Lopes, Marlene; Shrestha, Neha; Correia, Alexandra; Shahbazi, Mohammad-Ali; Sarmento, Bruno; Hirvonen, Jouni; Veiga, Francisco; Seiça, Raquel; Ribeiro, António; Santos, Hélder A

    2016-06-28

    The potential of nanoparticles (NPs) to overcome the barriers for oral delivery of protein drugs have led to the development of platforms capable of improving their bioavailability. However, despite the progresses in drug delivery technologies, the success of oral delivery of insulin remains elusive and the disclosure of insulin mechanisms of absorption remains to be clarified. To overcome multiple barriers faced by oral insulin and to enhance the insulin permeability across the intestinal epithelium, here insulin-loaded alginate/dextran sulfate (ADS)-NPs were formulated and dual-coated with chitosan (CS) and albumin (ALB). The nanosystem was characterized by its pH-sensitivity and mucoadhesivity, which enabled to prevent 70% of in vitro insulin release in simulated gastric conditions and allowed a sustained insulin release following the passage to simulated intestinal conditions. The pH and time-dependent morphology of the NPs was correlated to the release and permeation profile of insulin. Dual CS/ALB coating of the ADS-NPs demonstrated augmented intestinal interactions with the intestinal cells in comparison to the uncoated-NPs, resulting in a higher permeability of insulin across Caco-2/HT29-MTX/Raji B cell monolayers. The permeability of the insulin-loaded ALB-NPs was reduced after the temperature was decreased and after co-incubation with chlorpromazine, suggesting an active insulin transport by clathrin-mediated endocytosis. Moreover, the permeability inhibition with the pre-treatment with sodium chlorate suggested that the interaction between glycocalix and the NPs was critical for insulin permeation. Overall, the developed nanosystem has clinical potential for the oral delivery of insulin and therapy of type 1 diabetes mellitus. PMID:27074369

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

    PubMed

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

    2015-12-01

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

  10. Administration of Reconstituted Polyphenol Oil Bodies Efficiently Suppresses Dendritic Cell Inflammatory Pathways and Acute Intestinal Inflammation

    PubMed Central

    Cavalcanti, Elisabetta; Vadrucci, Elisa; Delvecchio, Francesca Romana; Addabbo, Francesco; Bettini, Simona; Liou, Rachel; Monsurrò, Vladia; Huang, Alex Yee-Chen; Pizarro, Theresa Torres

    2014-01-01

    Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs) in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation. PMID:24558444

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

    SciTech Connect

    Saburi, Wataru; Hondoh, Hironori; Unno, Hideaki; Okuyama, Masayuki; Mori, Haruhide; Nakada, Toshitaka; Matsuura, Yoshiki; Kimura, Atsuo

    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, c = 104.30 Å. A native data set was collected to 2.2 Å resolution from a single crystal.

  12. Effect of Diethylaminoethyl Dextran on the Growth of Mycoplasma in Agar

    PubMed Central

    Tauraso, Nicola M.

    1967-01-01

    The growth of certain strains of Mycoplasma is inhibited by substances present in commercial agar preparations. The addition of diethylaminoethyl (DEAE) dextran (10 mg per 100 ml) to agar media appears to enhance the growth of some strains. Of eight strains initially tested, the presence of DEAE dextran grossly enhanced the growth of three strains. One strain appeared not to be affected, and a clearly enhancing effect was not evident with four strains. Quantitative studies revealed that growth enhancement varied from 10 colony-forming units (CFU) for M. hominis type II (strain Campo) to 103.3 CFU for M. pulmonis (strain 880). The growth-enhancing effect is probably due to the ability of DEAE dextran to bind the sulfated polysaccharide moieties in agar and not to the DEAE dextran, per se. Images PMID:6025444

  13. Elongation of fibers from highly viscous dextran solutions enables fabrication of rapidly dissolving drug carrying fabrics.

    PubMed

    Frampton, John P; Lai, David; Lounds, Maxwell; Chung, Kyeongwoon; Kim, Jinsang; Mansfield, John F; Takayama, Shuichi

    2015-01-28

    A simple method is presented for forming thread-like fibers from highly viscous dextran solutions. Based on the cohesive and adhesive forces between a dextran solution and the substrate to which it is applied, multiple fibers of approximately 10 μm in diameter can be elongated simultaneously. These fibers can be woven into multiple layers to produce fabrics of varying fiber orientations and mechanical properties. Various bioactive agents can be incorporated into the dextran solution prior to fiber formation, including hemostatic and antibiotic agents. Fabrics containing thrombin are capable of coagulating human platelet poor plasma in vitro. Fabrics containing antibiotics are capable of suppressing bacterial growth in a disk diffusion assay. These data suggest that this new material composed entirely of dextran has promise as a drug delivery component in wound dressings.

  14. Inhibitory effect of substituted dextrans on MCF7 human breast cancer cell growth in vitro.

    PubMed

    Morere, J F; Letourneur, D; Planchon, P; Avramoglou, T; Jozefonvicz, J; Israel, L; Crepin, M

    1992-12-01

    Substituted dextrans can reproduce some of the properties of heparin and can thus be used to alter cellular growth. We studied the effect of heparin (H108), dextran (D), carboxymethylbenzylamide dextran (CMDB) and carboxymethylbenzylamide sulfonate dextran (CMDBS) on the growth of human mammary cells of the MCF7 tumor line. The cells were cultured in minimum Eagle's medium containing 2% fetal calf serum without biopolymer, or with increasing concentrations of H108, D, CMDB or CMDBS. Growth curves were accurately based on cell counting using a Coulter counter. Cell distribution in the various phases of the cycle was analyzed by flow cytometry. Dose-dependent growth inhibitory effects (400-4000 micrograms/ml) were observed. The effect on MCF7 tumor cells was most apparent with CMDBS. The percentage of cells in the S phase decreased with preferential blocking in the G0/G1 phase. Pre-clinical studies can be anticipated as there is an absence of in vivo toxicity.

  15. Sodium diethyldithiocarbamate

    Integrated Risk Information System (IRIS)

    Sodium diethyldithiocarbamate ; CASRN 148 - 18 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Non

  16. Sodium fluoroacetate

    Integrated Risk Information System (IRIS)

    Sodium fluoroacetate ; CASRN 62 - 74 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogen

  17. Sodium azide

    Integrated Risk Information System (IRIS)

    Sodium azide ; CASRN 26628 - 22 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  18. Acifluorfen, sodium

    Integrated Risk Information System (IRIS)

    Acifluorfen , sodium ; CASRN 62476 - 59 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcino

  19. Sodium cyanide

    Integrated Risk Information System (IRIS)

    Jump to main content . Integrated Risk Information System Recent Additions | Contact Us Search : All EPA IRIS • You are here : EPA Home • Research • Environmental Assessment • IRIS • IRIS Summaries Redirect Page As of September 28 , 2010 , the assessment summary for sodium cyanide is included in the

  20. Laser light scattering measurement of dextran-induced Streptococcus mutans aggregation.

    PubMed Central

    Ryan, V; Hart, T R; Schiller, R

    1980-01-01

    Intensity fluctuation spectroscopy was used to study dextran-induced aggregation of Streptococcus mutans bacteria. Smoluchowski's theory of colloidal flocculation provided a consistent model of the agglutination process. Our experiments indicated that aggregation was inhibited by the negatively charged surfaces of the cells, while dextran polymers effectively bound organisms together. Our experimental data were consistent with the quantitative predictions of a polymer bridge model of agglutination. PMID:6168309

  1. 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.

  2. Macromolecular leakage benath full cast crowns. Part II: The diffusion of lipopolysaccharide and dextran.

    PubMed

    Coleman, A J

    1996-01-01

    Fifteen extracted molars were prepared for crowns. Crowns with access ports (one facial, one lingual) were cast in gold. Teeth and crowns luted with provisional cement with filters inserted into the ports were immersed in a solution of labeled macromolecules (FITC-dextran, TRITC-LPS) and evaluated for leakage. Filters were retrieved and analyzed by use of fluorescent microscopy. Leakage of LPS and dextran occurred as early as 2 weeks beneath crowns luted with a provisional cement (NoGenol). PMID:8850458

  3. 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.

  4. 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. PMID:25196744

  5. Local and systemic antibody responses to dextran-cholera toxin B subunit conjugates.

    PubMed Central

    Bergquist, C; Lagergård, T; Lindblad, M; Holmgren, J

    1995-01-01

    This study was designed to test local and systemic immunity following mucosal immunization with a polysaccharide-protein conjugate. After preparing and characterizing dextran-cholera toxin B subunit (CTB) conjugates, we studied their immunogenicity in mice following systemic or mucosal immunizations. Dextran was chosen as a model polysaccharide antigen and conjugated via adipic acid dihydrazide and N-succinimidyl-3-(2-pyridyldithio)propionate to CTB. Mice were immunized either subcutaneously, intranasally, or perorally three times, and cholera toxin was used as an adjuvant for the mucosal immunizations. Three conjugates with different molecular weights for dextran (40,000 and 76,000) or varying dextran/CTB molar ratios were tested. Peroral immunizations with all conjugates evoked local immunoglobulin A (IgA) antibody responses against dextran in the small intestine, and intranasal immunizations did the same in the lung. Intranasal immunizations also elicited serum antibody titers that were significantly higher than or equal to those after subcutaneous immunizations. Intranasal immunizations evoked serum IgG antidextran titers which were dependent on the dextran/CTB molar ratio and inversely related to the local IgA response, which was not the case for subcutaneous immunizations. This is the first study of local and systemic immunity following mucosal immunization with a polysaccharide-protein conjugate. The results show that it is possible to evoke a local as well as a systemic antibody response against a polysaccharide by conjugating it to CTB and using an appropriate route of immunization. PMID:7537252

  6. Local and systemic antibody responses to dextran-cholera toxin B subunit conjugates.

    PubMed

    Bergquist, C; Lagergård, T; Lindblad, M; Holmgren, J

    1995-05-01

    This study was designed to test local and systemic immunity following mucosal immunization with a polysaccharide-protein conjugate. After preparing and characterizing dextran-cholera toxin B subunit (CTB) conjugates, we studied their immunogenicity in mice following systemic or mucosal immunizations. Dextran was chosen as a model polysaccharide antigen and conjugated via adipic acid dihydrazide and N-succinimidyl-3-(2-pyridyldithio)propionate to CTB. Mice were immunized either subcutaneously, intranasally, or perorally three times, and cholera toxin was used as an adjuvant for the mucosal immunizations. Three conjugates with different molecular weights for dextran (40,000 and 76,000) or varying dextran/CTB molar ratios were tested. Peroral immunizations with all conjugates evoked local immunoglobulin A (IgA) antibody responses against dextran in the small intestine, and intranasal immunizations did the same in the lung. Intranasal immunizations also elicited serum antibody titers that were significantly higher than or equal to those after subcutaneous immunizations. Intranasal immunizations evoked serum IgG antidextran titers which were dependent on the dextran/CTB molar ratio and inversely related to the local IgA response, which was not the case for subcutaneous immunizations. This is the first study of local and systemic immunity following mucosal immunization with a polysaccharide-protein conjugate. The results show that it is possible to evoke a local as well as a systemic antibody response against a polysaccharide by conjugating it to CTB and using an appropriate route of immunization. PMID:7537252

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    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.

  8. Cationic amphiphilic dextran hydrogels with potential biomedical applications.

    PubMed

    Mocanu, Georgeta; Nichifor, Marieta

    2014-01-01

    Dextran microparticles were chemically modified for the attachment of quaternary ammonium groups carrying substituents with different hydrophobicity, in order to obtain amphiphilic cationic hydrogels with different hydrophilic/lipophilic balance. These hydrogels retain various amounts of dyes: Rose Bengal, Brilliant Blue and Vitamin B12, used as models for hydrophobic, amphiphilic and hydrophilic drugs, as a function of their hydrophilic/hydrophobic properties. Bovine serum albumin (BSA) retention by hydrogels occurs in higher amounts at pH 6.9, and is influenced by electrostatic, hydrophobic forces and the swelling of the supports. Tetanus anatoxin is retained by the supports through electrostatic and/or hydrophobic forces, in amounts varying between 110 and 200 mg/g. Both proteins are gradually released, through increasing of the eluent ionic strengths. Alpha-tocopherol is retained by the hydrogels preponderantly through hydrophobic forces, in amounts varying between 130 and 300 mg/g. Measurement of the scavenging effect proved the antioxidant properties of the included drug. Based on the obtained results, one can appreciate the potential of the synthesized cationic hydrogels as supports for biomolecules or as vaccine adjuvants.

  9. Cell-specific cytotoxicity of dextran-stabilized magnetite nanoparticles.

    PubMed

    Ding, Jing; Tao, Ke; Li, Jiyu; Song, Sheng; Sun, Kang

    2010-08-01

    Cytotoxicity of dextran-hybridized magnetite nanoparticles which were prepared by a novel polyol method was evaluated by incubation with four different kinds of cells, including rat liver cells BRL 3A, renal cells NRK, astrocyte and periphery blood mononuclear cells (PBMC). The study was designed not only to evaluate their cytotoxicity but also to reflect the interaction between nanoparticles and related cells in their circulation processes. By fluorescent-activated cell sorting technique, it was found that the cytotoxicity of the nanoparticles is cell-specific. Under the concentrations in our study (0-128 mg/mL), the nanoparticles lead to the apoptosis of PBMC in a concentration-dependant manner, but have almost no influence on the other kinds of cells. TEM images demonstrate that the nanoparticles were endocytosed by BRL 3A, NRK and astrocyte, and result in the apoptosis of PBMC without the observation of the uptaking process. The results suggest that the related cells in nanoparticles cycling process should also be concerned for the cytotoxicity evaluation.

  10. Covalent immobilization of Enterococcus faecalis Esawy dextransucrase and dextran synthesis.

    PubMed

    Hashem, Amal M; Gamal, Amira A; Hassan, Mohamed E; Hassanein, Naziha M; Esawy, Mona A

    2016-01-01

    Enterococcus faecalis Esawy dextransucrase was immobilized in Fe(3+)-cross-linked alginate/carboxymethyl cellulose (AC) beads. The gel beads were modified with polyethylenimine (PEI) followed by glutaraldehyde (GA) to form Fe(3+) (ACPG) beads. Fe(3+) (ACPG) was characterized using FTIR and DSC techniques. GA activated beads showed new two peaks. The first was at 1,717 cm(-1) which refers to (CO) group of a free aldehyde end of glutaraldehyde, and another peak was at 1,660 cm(-1) referring to (CN) group. The immobilization process improved the optimum temperature from 35 to 45°C. The immobilized enzyme showed its optimum activity in wide pH range (4.5-5.4) compared to pH 5.4 in case of free form. Also, the immobilization process improved the thermal and pH enzyme stability to great extent. Reusability test proved that the enzyme activity retained 60% after 15 batch reactions. Immobilized enzyme was applied successfully in the synthesis of oligosaccharides and different molecular weights of dextran.

  11. Thermally controlled protein release from gelatin dextran hydrogels

    NASA Astrophysics Data System (ADS)

    Aso, Y.; Yoshioka, S.; Nakai, Y.; Kojima, S.

    1999-06-01

    Biodegradable hydrogels in which drug release was controlled by sol-gel transition were prepared. Gelatin was used as a component because it exhibits sol-gel transition in response to temperature changes. Glycidyl methacrylated (GMA) dextran was crosslinked by low dose γ-irradiation in the presence of gelatin and the model drugs, β-galactosidase ( β-GA), bovine serum albumin (BSA) or 5-fluorouracil (5-FU). The enzyme activity of β-GA remained greater than 95% after irradiation. Temperature-responsive release of β-GA and BSA resulted from the sol-gel transition of gelatin. Sol-gel transition was confirmed by the temperature dependence of the spin-spin relaxation time of the gel polymer protons. The protein release rate was affected by both the degree of GMA substitution and the gelatin concentration. Desired release rate could be achieved by adjusting these factors. The release rate of 5-FU was not affected by the sol-gel transition of gelatin.

  12. Renal Blood Flow Response to Angiotensin 1-7 versus Hypertonic Sodium Chloride 7.5% Administration after Acute Hemorrhagic Shock in Rats.

    PubMed

    Maleki, Maryam; Nematbakhsh, Mehdi

    2016-01-01

    Background. Angiotensin 1-7 (Ang1-7) plays an important role in renal circulation. Hemorrhagic shock (HS) may cause kidney circulation disturbance, and this study was designed to investigate the renal blood flow (RBF) response to Ang1-7 after HS. Methods. 27 male Wistar rats were subjected to blood withdrawal to reduce mean arterial pressure (MAP) to 45 mmHg for 45 min. The animals were treated with saline (group 1), Ang1-7 (300 ng·kg(-1) min(-1)), Ang1-7 in hypertonic sodium chloride 7.5% (group 3), and hypertonic solution alone (group 4). Results. MAP was increased in a time-related fashion (P time < 0.0001) in all groups; however, there was a tendency for the increase in MAP in response to hypertonic solution (P = 0.09). Ang1-7, hypertonic solution, or combination of both increased RBF in groups 2-4, and these were significantly different from saline group (P = 0.05); that is, Ang1-7 leads to a significant increase in RBF to 1.35 ± 0.25 mL/min compared with 0.55 ± 0.12 mL/min in saline group (P < 0.05). Conclusion. Although Ang1-7 administration unlike hypertonic solution could not elevate MAP after HS, it potentially could increase RBF similar to hypertonic solution. This suggested that Ang1-7 recovers RBF after HS when therapeutic opportunities of hypertonic solution are limited.

  13. Renal Blood Flow Response to Angiotensin 1-7 versus Hypertonic Sodium Chloride 7.5% Administration after Acute Hemorrhagic Shock in Rats

    PubMed Central

    Maleki, Maryam; Nematbakhsh, Mehdi

    2016-01-01

    Background. Angiotensin 1-7 (Ang1-7) plays an important role in renal circulation. Hemorrhagic shock (HS) may cause kidney circulation disturbance, and this study was designed to investigate the renal blood flow (RBF) response to Ang1-7 after HS. Methods. 27 male Wistar rats were subjected to blood withdrawal to reduce mean arterial pressure (MAP) to 45 mmHg for 45 min. The animals were treated with saline (group 1), Ang1-7 (300 ng·kg−1 min−1), Ang1-7 in hypertonic sodium chloride 7.5% (group 3), and hypertonic solution alone (group 4). Results. MAP was increased in a time-related fashion (Ptime < 0.0001) in all groups; however, there was a tendency for the increase in MAP in response to hypertonic solution (P = 0.09). Ang1-7, hypertonic solution, or combination of both increased RBF in groups 2-4, and these were significantly different from saline group (P = 0.05); that is, Ang1-7 leads to a significant increase in RBF to 1.35 ± 0.25 mL/min compared with 0.55 ± 0.12 mL/min in saline group (P < 0.05). Conclusion. Although Ang1-7 administration unlike hypertonic solution could not elevate MAP after HS, it potentially could increase RBF similar to hypertonic solution. This suggested that Ang1-7 recovers RBF after HS when therapeutic opportunities of hypertonic solution are limited. PMID:27073699

  14. Test Your Sodium Smarts

    MedlinePlus

    ... You may be surprised to learn how much sodium is in many foods. Sodium, including sodium chloride ... foods with little or no salt. Test your sodium smarts by answering these 10 questions about which ...

  15. Low sodium diet (image)

    MedlinePlus

    ... for you. Look for these words on labels: low-sodium, sodium-free, no salt added, sodium-reduced, or ... for you. Look for these words on labels: low-sodium, sodium-free, no salt added, sodium-reduced, or ...

  16. 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. PMID:27155914

  17. Activation of Human Complement System by Dextran-Coated Iron Oxide Nanoparticles Is Not Affected by Dextran/Fe Ratio, Hydroxyl Modifications, and Crosslinking

    PubMed Central

    Wang, Guankui; Chen, Fangfang; Banda, Nirmal K.; Holers, V. Michael; Wu, LinPing; Moghimi, S. Moein; Simberg, Dmitri

    2016-01-01

    While having tremendous potential as therapeutic and imaging tools, the clinical use of engineered nanoparticles has been associated with serious safety concerns. Activation of the complement cascade and the release of proinflammatory factors C3a and C5a may contribute to infusion-related reactions, whereas opsonization with C3 fragments promotes rapid recognition and clearance of nanomaterials by mononuclear phagocytes. We used dextran-coated superparamagnetic iron oxide nanoparticles (SPIO), which are potent activators of the complement system, to study the role of nanoparticle surface chemistry in inciting complement in human serum. Using complement inhibitors and measuring levels of fluid phase markers (sC5b-9, C5a, and Bb), we found that the majority of human complement activation by SPIO is through the alternative pathways (AP). SPIO prepared with high dextran/iron ratio showed some complement activation via calcium-sensitive pathways, but the AP was responsible for the bulk of complement activation and amplification. Activation via the AP required properdin, the positive regulator of the alternative C3bBb convertase. Modification of sugar alcohols of dextran with alkylating, acylating, or crosslinking agents did not overcome complement activation and C3 opsonization. These data demonstrate that human complement activation is independent of dextran modification of SPIO and suggest a crucial role of the AP in immune recognition of nano-assemblies in human serum. PMID:27777575

  18. Surface forces and protein adsorption on dextran- and polyethylene glycol-modified polydimethylsiloxane.

    PubMed

    Farrell, Megan; Beaudoin, Stephen

    2010-12-01

    Dextran and polyethylene glycol (PEG) are often covalently bound to the surface of polydimethylsiloxane (PDMS) for the purpose of modifying its hydrophilicity and biocompatibility. In this work, the effects of the dextran and PEG on the morphology, wetting, and surface charge of the resulting surfaces were quantified and correlated with changes in the amount of fibrinogen and albumin adsorbed from aqueous solution. PDMS films were functionalized in a microwave oxygen plasma to create surface hydroxyl groups that were subsequently aminated by incubation in a (3-aminopropyl)trimethoxysilane (APTES) solution. Oxidized dextran and PEG-aldehyde were linked to the surface amines via reductive amination. This process resulted in low surface coverage of immobilized PEG in the end-on conformation and a more uniform and dense distribution of side-on immobilized dextran. The immobilized dextran reduced the contact angle of the PDMS film from 109° to 80° and neutralized the zeta potential over the pH range from 3 to 11. An atomic force microscope was used to measure the interaction force between the modified PDMS and a model hydrophobic surface (polystyrene latex) and a model hydrophilic surface (silica) in aqueous solution to show that van der Waals and hydrophobic attractive forces are the dominant forces for protein adsorption in this system. The PEG- and dextran-modified PDMS were exposed to BSA and fibrinogen to test their resistance to protein adsorption. The coatings were ineffective at reducing the adsorption of either molecule, and the dextran-modification of the PDMS caused more BSA to adsorb than in the case of the unmodified PDMS. PMID:20801620

  19. Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers.

    PubMed

    Nielsen, Thorbjørn Terndrup; Amiel, Catherine; Duroux, Laurent; Larsen, Kim Lambertsen; Städe, Lars Wagner; Wimmer, Reinhard; Wintgens, Véronique

    2015-01-01

    Novel (S)-camptothecin-dextran polymers were obtained by "click" grafting of azide-modified (S)-camptothecin and alkyne-modified dextrans. Two series based on 10 kDa and 70 kDa dextrans were prepared with a degree of substitution of (S)-camptothecin between 3.1 and 10.2%. The binding properties with β-cyclodextrin and β-cyclodextrin polymers were measured by isothermal titration calorimetry and fluorescence spectroscopy, showing no binding with β-cyclodextrin but high binding with β-cyclodextrin polymers. In aqueous solution nanoparticles were formed from association between the (S)-camptothecin-dextran polymers and the β-cyclodextrin polymers.

  20. 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.

  1. Structural analysis of dextran-based hydrogels obtained chemoenzymatically.

    PubMed

    Ferreira, L; Figueiredo, M M; Gil, M H; Ramos, M A

    2006-04-01

    This work reports the results of structural analysis in novel dextran-acrylate (dexT70-VA) hydrogels generated chemoenzymatically. Porous structure as well as hydrogel surface and interior morphologies were evaluated by mercury intrusion porosimetry (MIP), nitrogen adsorption (NA), and scanning electron microscopy (SEM) analyses, as a function of the degree of substitution (DS), and initial water content used in the preparation of the hydrogel. MIP analysis showed that the overall networks were clearly macroporous with pore sizes ranging from 0.065 to 10 microm. As expected, the average pore size decreased as DS increased and as initial water content decreased. Moreover, the porosity values ranged from 75 up 90%, which shows that these hydrogels present an interconnected pore structure. Nitrogen adsorption analyses showed that the specific surface area of dexT70-VA hydrogels increased either by increasing the DS or by decreasing the initial water content of the hydrogel. SEM results revealed that the surface of hydrogels with lower DS presented either a porous structure or a polymeric "skin" covering the pores, whereas hydrogels with higher DS were totally porous. Furthermore, the interior morphology varied according to the DS and the initial water content of the hydrogels. Finally, the average pore size was also determined from the swelling of hydrogel using a theoretical model developed by Flory-Rehner. The comparison of the SEM and MIP results with the ones obtained by the equilibrium swelling theory of Flory-Rehner shows that this approach highly underestimates the average pore size. PMID:16211568

  2. Effects of dextran on the molecular structure and tensile behaviour of human fibrin.

    PubMed

    Dhall, T Z; Bryce, W A; Dhall, D P

    1976-06-30

    Characteristic changes induced by dextran during the conversion of fibrinogen to fibrin have previously been shown to be associated with profound alterations in morphology of fibrin. However, whether dextran is incorporated into the fibrin molecule and whether morphological changes are associated with alterations in mechanical behaviour of formed fibrin was unclear. The investigations described show that the fibrin made in the presence of dextran has a shortened syneresis time, a lowered modulus of elasticity, an increased elongation and diminished ultimate strength at break. The molecular composition of fibrin clots remains unaltered despite the altered mechanical properties and morphological changes. Furthermore, dextran is not incorporated into the fibrin structure in any appreciable quantity. It is suggested that these several effects of dextran on clot morphology, tensile behaviour and kinetics of fibrin formation arise from increased forces of attraction between fibrin molecules such that fibrin chains are held together by weak secondary cross-links rather than by stronger primary cross-links which are hidden within the thicker fibrin chain bundles.

  3. Human plasma protein adsorption onto dextranized surfaces: a two-dimensional electrophoresis and mass spectrometry study.

    PubMed

    Tsai, Irene Y; Tomczyk, Nancy; Eckmann, Joshua I; Composto, Russell J; Eckmann, David M

    2011-05-01

    Protein adsorption is fundamental to thrombosis and to the design of biocompatible materials. We report a two-dimensional electrophoresis and mass spectrometry study to characterize multiple human plasma proteins adsorbed onto four different types of model surfaces: silicon oxide, dextranized silicon, polyurethane and dextranized polyurethane. Dextran was grafted onto the surfaces of silicon and polyurethane to mimic the blood-contacting endothelial cell glycocalyx surface. Surface topography and hydrophobicity/hydrophilicity were determined and analyzed using atomic force microscopy and water contact angle measurements, respectively. Using two-dimensional electrophoresis, we show that, relative to the unmodified surfaces, dextranization significantly inhibits the adsorption of several human plasma proteins including IGHG1 protein, fibrinogen, haptoglobin, Apo A-IV, Apo A-I, immunoglobulin, serum retinal-binding protein and truncated serum albumin. We further demonstrate the selectivity of plasma protein adsorbed onto the different functionalized surfaces and the potential to control and manipulate proteins adsorption on the surfaces of medical devices, implants and microfluidic devices. This result shows that adsorption experiments using a single protein or a binary mixture of proteins are consistent with competitive protein adsorption studies. In summary, these studies indicate that coating blood-contacting biomedical applications with dextran is an effective route to reduce thrombo-inflammatory responses and to surface-direct biological activities. PMID:21277175

  4. 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.

  5. Preparation of pH-Sensitive Dextran Nanoparticle for Doxorubicin Delivery.

    PubMed

    Wang, Bi; Liu, Peng; Shi, Bihua; Gao, Jihua; Gong, Ping

    2015-04-01

    One of challenge for cancer therapy is efficient delivery of anticancer agents into tumor sites to increase efficiency of drugs and reduce side effects. To overcome this challenge, we designed pH- sensitive doxorubicin prodrug (DEX-PEI-DOX) nanoparticles based on dextran-poly(ethylene imine) copolymers (DEX-PEI). The DEX-PEI-DOX conjugates were conveniently prepared by grafting PEI to dextran, and then anticancer drug doxorubicin (DOX) were conjugated to DEX-PEI through acid cleavable cis-aconityl bonds. The experiments of dynamic light scattering (DLS) and transmission electron microscopy (TEM) represented that size of dextran nanoparticles was about 120 nm with uniform spherical shape. In vitro drug release from self-assembled nanoparticles was dependent on the pH of medium due to the cis-aconityl linkage. Confocal images revealed that dextran based pH-sensitive DOX delivery nanoparticle could enter into Human breast carcinoma (MCF-7) cells easily. Therapeutic efficacy against MCF-7 cells in vitro was evaluated through MTT assays and the results showed that dextran nanoparticle had obvious anticancer ability. All above results indicated this pH-sensitive DOX-loaded nanoparticles system would be a useful candidate for cancer therapy. PMID:26353472

  6. Antiviral activity of derivatized dextrans on HIV-1 infection of primary macrophages and blood lymphocytes.

    PubMed

    Seddiki, N; Mbemba, E; Letourneur, D; Ylisastigui, L; Benjouad, A; Saffar, L; Gluckman, J C; Jozefonvicz, J; Gattegno, L

    1997-11-28

    The present study demonstrates at the molecular level that dextran derivatives carboxymethyl dextran benzylamine (CMDB) and carboxymethyl dextran benzylamine sulfonate (CMDBS), characterized by a statistical distribution of anionic carboxylic groups, hydrophobic benzylamide units, and/or sulfonate moieties, interact with HIV-1 LAI gp120 and V3 consensus clades B domain. Only limited interaction was observed with carboxy-methyl dextran (CMD) or dextran (D) under the same conditions. CMDBS and CMDB (1 microM) strongly inhibited HIV-1 infection of primary macrophages and primary CD4+ lymphocytes by macrophage-tropic and T lymphocyte-tropic strains, respectively, while D or CMD had more limited effects on M-tropic infection of primary macrophages and exert no inhibitory effect on M- or T-tropic infection of primary lymphocytes. CMDBS and CMDB (1 microM) had limited but significant effect on oligomerized soluble recombinant gp120 binding to primary macrophages while they clearly inhibit (> 50%) such binding to primary lymphocytes. In conclusion, the inhibitory effect of CMDB and the CMDBS, is observed for HIV M- and T-tropic strain infections of primary lymphocytes and macrophages which indicates that these compounds interfere with steps of HIV replicative cycle which neither depend on the virus nor on the cell.

  7. Metallization and biopatterning on ultra-flexible substrates via dextran sacrificial layers.

    PubMed

    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

  8. 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

  9. Low dietary sodium is anxiogenic in rats.

    PubMed

    Leshem, M

    2011-07-01

    It is commonly believed that salt intake is required solely to maintain mineralofluid balance, and that its excessive intake is pathophysiological. Yet, apart from the increased intake of sodium-rich foods caused by perinatal sodium loss, the determinants of human salt intake, its excess and persistence, are unknown. One suggestion is that high salt intake may be adaptive in coping with daily adversity. Therefore, we investigated the effect of low dietary sodium in models of depression and anxiety, on chronic mild stress (CMS), and on acute unpredictable stressors. We find that low dietary sodium exacerbates anxiety in the elevated maze and open field. However, it does not exacerbate modeled depression or anxiety in chronically and acutely stressed rats. We find that CMS-induced anhedonia reduces 1.5% NaCl as well as 5% sucrose intake. The reduction in NaCl intake is specific to depression insofar as it did not occur after repeated acute stressors. The reduction occurred despite sodium restriction. Thus while sodium restriction is anxiogenic, it does not exacerbate preexisting depression or anxiety in clearly demarcated behavioral models. These psychological dimensions of salt intake are only now being addressed experimentally, and the ramifications for its control, and for individuals vulnerable to depression or stress, require clarification.

  10. In Vivo Ocular Fluorophotometry: Delivery of Fluoresceinated Dextrans via Transscleral Diffusion in Rabbits

    PubMed Central

    Berezovsky, Damian E.; Patel, Samirkumar R.; McCarey, Bernard E.

    2011-01-01

    Purpose. To evaluate the transscleral delivery of fluoresceinated dextrans (FITC-D) with molecular mass up to 70 kDa to the rabbit posterior segment using sub-Tenon injections. Methods. Eighteen NZW rabbits received a unilateral 200-μL injection of 2 mg/mL sodium fluorescein (NaF), 25 mg/mL 40-kDa FITC-D, or 25 mg/mL 70-kDa FITC-D, with (n = 9) or without (n = 9) immediate euthanatization. In live animals, fluorescence was measured in the retina/choroid and mid-vitreous by fluorophotometry, immediately after injection and after 4, 24, 48, and 72 hours. Euthanatized animals were examined hourly through 5 or 6 hours. Results. In live animals, the average peak NaF concentration in the retina/choroid was 310.2 ng/mL, measured 3 hours after injection. Average 40- and 70-kDa FITC-D concentrations in the retina/choroid peaked at 5409.6 and 2375.6 ng/mL, respectively, 24 hours after injection. Fluorescence returned to baseline levels 6 hours after NaF injection, and 48 and 72 hours after 40- and 70-kDa FITC-D injections, respectively. Rabbits that received NaF followed by euthanatization exhibited a continuous increase in retina/choroid and mid-vitreous fluorescence, beginning 1 hour after injection, whereas FITC-D-injected eyes did not show elevated retina/choroid or mid-vitreous fluorescence through 6 hours. Conclusions. FITC-D weighing up to 70-kDa, as well as NaF, reached the posterior retina/choroid after sub-Tenon injections in live rabbits. NaF and 40-kDa FITC-D reached higher peak concentrations and were cleared from the eye more rapidly than was 70-kDa FITC-D. There was minimal penetration of NaF and FITC-D into the mid-vitreous in the in vivo experiments. PMID:21791594

  11. Aminoalkyl functionalization of dextran for coupling of bioactive molecules and nanostructure formation.

    PubMed

    Fiege, Kathrin; Lünsdorf, Heinrich; Mischnick, Petra

    2013-06-01

    Aminopropyl dextrans and mixed aminopropyl cyanoethyl dextrans were prepared from cyanoethyl precursors by full or partial reduction with CoCl2/NaBH4. Coupling of various aldehydes to the glucan backbone by reductive amination was accomplished with 4-hydroxy-3-methoxybenzaldehyde (vanillin), 3,5-di-tert-butyl-4-hydroxy-benzaldehyde (BHT-CHO), maltose and maltotriose, and picoline borane as reducing agent. Successful coupling of these representatives for aroma compounds, antioxidants and sugar side-chains were verified by ESI-MS after hydrolysis and by 1D and 2D NMR spectroscopy. Degree of conversion (molar ratio of coupled aldehydes) was estimated from (1)H NMR spectra. Formation of secondary and tertiary amines was detectd by ESI-MS. Applying a solvent exchange process, new nanoparticles based on these modified dextrans were prepared with and without addition of iron oxide nanoparticles. PMID:23618308

  12. THE UPTAKE OF IRON IN RABBIT SYNOVIAL TISSUE FOLLOWING INTRA-ARTICULAR INJECTION OF IRON DEXTRAN

    PubMed Central

    Ball, J.; Chapman, J. A.; Muirden, K. D.

    1964-01-01

    Iron dextran (molecular weight 7,000) diffuses rapidly from the joint cavity through the synovium, along lymphatics and extracellular tissue spaces; articular cartilage is impermeable to iron dextran. There is also rapid cellular uptake by synovial lining cells, particularly of the vacuolar type; endoplasmic reticulum-containing lining cells rarely take up iron dextran. Cellular uptake is probably effected by pseudopodial folds projecting from the cell surface and enclosing extracellular material. Cells containing iron may degenerate and be ingested by phagocytes, and this may account for the concentration of iron in a smaller proportion of cells on or below the synovial surface in the later stages. At 6 to 18 hours after injection there is a mild inflammatory reaction and some synovial proliferation; from this stage onwards intracellular iron occurs in the form of haemosiderin. Granules of haemosiderin are present in the synovium 3 months after injection and possibly longer. PMID:14203385

  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. Hypertonic Saline Dextran Ameliorates Organ Damage in Beagle Hemorrhagic Shock

    PubMed Central

    You, Guo-xing; Wang, Ying; Chen, Gan; Wang, Quan; Zhang, Xi-gang; Zhao, Lian; Zhou, Hong; He, Yue-zhong

    2015-01-01

    Objective The goal of this study was to investigate the effect of hypertonic saline with 6% Dextran-70 (HSD) resuscitation on organ damage and the resuscitation efficiency of the combination of HSD and lactated ringers (LR) in a model of hemorrhage shock in dogs. Methods Beagles were bled to hold their mean arterial pressure (MAP) at 50±5 mmHg for 1 h. After hemorrhage, beagles were divided into three groups (n = 7) to receive pre-hospital resuscitation for 1 h (R1): HSD (4 ml/kg), LR (40 ml/kg), and HSD+LR (a combination of 4 ml/kg HSD and 40 ml/kg LR). Next, LR was transfused into all groups as in-hospital resuscitation (R2). After two hours of observation (R3), autologous blood was transfused. Hemodynamic responses and systemic oxygenation were measured at predetermined phases. Three days after resuscitation, the animals were sacrificed and tissues including kidney, lung, liver and intestinal were obtained for pathological analysis. Results Although the initial resuscitation with HSD was shown to be faster than LR with regard to an ascending MAP, the HSD group showed a similar hemodynamic performance compared to the LR group throughout the experiment. Compared with the LR group, the systemic oxygenation performance in the HSD group was similar but showed a lower venous-to-arterial CO2 gradient (Pv-aCO2) at R3 (p < 0.05). Additionally, the histology score of the kidneys, lungs and liver were significantly lower in the HSD group than in the LR group (p < 0.05). The HSD+LR group showed a superior hemodynamic response but higher extravascular lung water (EVLW) and lower arterial oxygen tension (PaO2) than the other groups (p < 0.05). The HSD+LR group showed a marginally improved systemic oxygenation performance and lower histology score than other groups. Conclusions Resuscitation after hemorrhagic shock with a bolus of HSD showed a similar hemodynamic response compared with LR at ten times the volume of HSD, but HSD showed superior efficacy in organ protection

  15. Effect of sodium tetraborate (borax) on the thermal properties of frozen aqueous sugar and polyol solutions.

    PubMed

    Izutsu, Ken-ichi; Rimando, Annie; Aoyagi, Nobuo; Kojima, Shigeo

    2003-06-01

    The effect of sodium tetraborate (Na(2)B(4)O(7), borax) on the thermal property of frozen aqueous sugar and polyol solutions was studied through thermal analysis. Addition of borax raised the thermal transition temperature (glass transition temperature of maximally freeze-concentrated solutes; T(g)') of frozen sucrose solutions depending on the borax/sucrose concentration ratios. Changes in the T(g)' of frozen mono- and disaccharide solutions suggested various forms of complexes, including those of a borate ion and two saccharide molecules. Borax exerted the maximum effect to raise the oligosaccharide and dextran T(g)'s at borax/saccharide molar ratios of approximately 1-2 (maltose and maltooligosaccharides), 2 (dextran 1060), 5 (dextran 4900), and 10 (dextran 10200). Further addition of borax lowered T(g)'s of the saccharide solutions. Borax also raised T(g) and T(g)' temperatures of frozen aqueous glycerol solutions. The decreased solute mobility in frozen solutions by the borate-polyol complexes suggested higher collapse temperature in the freeze-drying process and improved stability of biological systems in frozen solutions.

  16. Effect of Microstructure on Population Growth Parameters of Escherichia coli in Gelatin-Dextran Systems

    PubMed Central

    Boons, Kathleen; Noriega, Estefanía; Van den Broeck, Rob; David, Charlotte C.; Hofkens, Johan

    2014-01-01

    Current literature acknowledges the effect of food structure on bacterial dynamics. Most studies introduce this “structure” factor using a single gelling agent, resulting in a homogeneous environment, whereas in practice most food products are heterogeneous. Therefore, this study focuses on heterogeneous protein-polysaccharide mixtures, based on gelatin and dextran. These mixtures show phase separation, leading to a range of heterogeneous microstructures by adjusting relative concentrations of both gelling agents. Based on confocal microscope observations, the growth of Escherichia coli in gelatin-dextran systems was observed to occur in the dextran phase. To find a relation between microscopic and population behavior, growth experiments were performed in binary and singular gelatin-dextran systems and culture broth at 23.5°C, with or without adding 2.9% (wt/vol) NaCl. The Baranyi and Roberts growth model was fitted to the experimental data and parameter estimates were statistically compared. For salted binary mixtures, a decrease in the population maximum cell density was observed with increasing gelatin concentration. In this series, for one type of microstructure, i.e., a gelatin matrix phase with a disperse dextran phase, the maximum cell density decreased with decreasing percentage of dextran phase. However, this relation no longer held when other types of microstructure were observed. Compared to singular systems, adding a second gelling agent in the presence of NaCl had an effect on population lag phases and maximum cell densities. For unsalted media, the growth parameters of singular and binary mixtures were comparable. Introducing this information into mathematical models leads to more reliable growth predictions and enhanced food safety. PMID:24951795

  17. Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing

    PubMed Central

    Sun, Guoming; Zhang, Xianjie; Shen, Yu-I; Sebastian, Raul; Dickinson, Laura E.; Fox-Talbot, Karen; Reinblatt, Maura; Steenbergen, Charles; Harmon, John W.; Gerecht, Sharon

    2011-01-01

    Neovascularization is a critical determinant of wound-healing outcomes for deep burn injuries. We hypothesize that dextran-based hydrogels can serve as instructive scaffolds to promote neovascularization and skin regeneration in third-degree burn wounds. Dextran hydrogels are soft and pliable, offering opportunities to improve the management of burn wound treatment. We first developed a procedure to treat burn wounds on mice with dextran hydrogels. In this procedure, we followed clinical practice of wound excision to remove full-thickness burned skin, and then covered the wound with the dextran hydrogel and a dressing layer. Our procedure allows the hydrogel to remain intact and securely in place during the entire healing period, thus offering opportunities to simplify the management of burn wound treatment. A 3-week comparative study indicated that dextran hydrogel promoted dermal regeneration with complete skin appendages. The hydrogel scaffold facilitated early inflammatory cell infiltration that led to its rapid degradation, promoting the infiltration of angiogenic cells into the healing wounds. Endothelial cells homed into the hydrogel scaffolds to enable neovascularization by day 7, resulting in an increased blood flow significantly greater than treated and untreated controls. By day 21, burn wounds treated with hydrogel developed a mature epithelial structure with hair follicles and sebaceous glands. After 5 weeks of treatment, the hydrogel scaffolds promoted new hair growth and epidermal morphology and thickness similar to normal mouse skin. Collectively, our evidence shows that customized dextran-based hydrogel alone, with no additional growth factors, cytokines, or cells, promoted remarkable neovascularization and skin regeneration and may lead to novel treatments for dermal wounds. PMID:22171002

  18. Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing.

    PubMed

    Sun, Guoming; Zhang, Xianjie; Shen, Yu-I; Sebastian, Raul; Dickinson, Laura E; Fox-Talbot, Karen; Reinblatt, Maura; Steenbergen, Charles; Harmon, John W; Gerecht, Sharon

    2011-12-27

    Neovascularization is a critical determinant of wound-healing outcomes for deep burn injuries. We hypothesize that dextran-based hydrogels can serve as instructive scaffolds to promote neovascularization and skin regeneration in third-degree burn wounds. Dextran hydrogels are soft and pliable, offering opportunities to improve the management of burn wound treatment. We first developed a procedure to treat burn wounds on mice with dextran hydrogels. In this procedure, we followed clinical practice of wound excision to remove full-thickness burned skin, and then covered the wound with the dextran hydrogel and a dressing layer. Our procedure allows the hydrogel to remain intact and securely in place during the entire healing period, thus offering opportunities to simplify the management of burn wound treatment. A 3-week comparative study indicated that dextran hydrogel promoted dermal regeneration with complete skin appendages. The hydrogel scaffold facilitated early inflammatory cell infiltration that led to its rapid degradation, promoting the infiltration of angiogenic cells into the healing wounds. Endothelial cells homed into the hydrogel scaffolds to enable neovascularization by day 7, resulting in an increased blood flow significantly greater than treated and untreated controls. By day 21, burn wounds treated with hydrogel developed a mature epithelial structure with hair follicles and sebaceous glands. After 5 weeks of treatment, the hydrogel scaffolds promoted new hair growth and epidermal morphology and thickness similar to normal mouse skin. Collectively, our evidence shows that customized dextran-based hydrogel alone, with no additional growth factors, cytokines, or cells, promoted remarkable neovascularization and skin regeneration and may lead to novel treatments for dermal wounds. PMID:22171002

  19. 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.

  20. Synthesis and characterization of dextran coated magnetite nanoparticles for diagnostics and therapy

    PubMed Central

    Khalkhali, Maryam; Sadighian, Somayeh; Rostamizadeh, Kobra; Khoeini, Farhad; Naghibi, Mehran; Bayat, Nahid; Habibizadeh, Mina; Hamidi, Mehrdad

    2015-01-01

    Introduction: Expansion of efficacious theranostic systems is of pivotal significance for medicine and human healthcare. Magnetic nanoparticles (MNPs) are known as drug delivery system and magnetic resonance imaging (MRI) contrast agent. MNPs as drug carriers have attracted significant attention because of the delivery of drugs loaded onto MNPs to solid tumors, maintaining them in the target site by an external electromagnetic field, and subsequently releasing drugs in a controlled manner. On the other hand, it is believed that MNPs possess high potential as MRI contrast agents. The aim of this work was to payload curcumin into dextran coated MNPs and investigate their potential as theranostic systems for controlled drug delivery and MRI imaging. Methods: MNPs were synthesized as a core and coated with dextran as polymeric shell to provide steric stabilization. Curcumin as anticancer drug was selected to be loaded into NPs. To characterize the synthesized NPs, various techniques (e.g., DLS, FESEM, FT-IR, XRD, and VSM) were utilized. In vitro drug release of curcumin was evaluated at 37˚C at the pH value of 5.4 and 7.4.The feasibility of employment of dextran coated MNPs as MRI contrast agents were also studied. Results: Formulations prepared from dextran coated MNPs showed high loading (13%) and encapsulation efficiency (95%). In vitro release study performed in the phosphate-buffered saline (PBS, pH= 7.4, 5.4) revealed that the dextran coated MNPs possess sustained release behavior at least for 4 days with the high extent of drug release in acidic media. Vibrating sample magnetometer (VSM) analysis proved the superparamagnetic properties of the dextran coated MNPs with relatively high-magnetization value indicating that they were sufficiently sensitive to external magnetic fields as magnetic drug carriers. Furthermore, dextran coated MNPs exhibited high potential as T2 contrast agents for MRI. Conclusion: Based on our findings, we propose the dextran coated MNPs

  1. [Effect of dextran of 250.000 molecular weight on experimental cholesterin-sclerosis in rabbits].

    PubMed

    Ferenc, S; Arpád, H; Gábor, L

    1976-07-01

    Effect of dextran of 250000 molecular weight on experimental cholesterin-sclerosis of rabbits was studied. Doses of 120 (mg/week) kg and 1200 (mg/week) kg administered during 12 weeks have resulted a protective effect. When doses of 1200 (mg/week) kg have been administered--in the aortic adventitia intensive cellular reaction, no hitherto described was revealed, which was considered to be a sing of the exhaustion of RES. This publication authors regard as a preliminary one. To clear whether the cellular reaction observed is a dextran-specific or macro-moleculespecific one further investigations are needed.

  2. Preventive use of Lactobacillus plantarum LS/07 and inulin to relieve symptoms of acute colitis.

    PubMed

    Hijová, Emília; Šoltésová, Alena; Salaj, Rastislav; Kuzma, Jozef; Strojný, Ladislav; Bomba, Alojz; Gregová, Kristína

    2015-01-01

    The aim of presented study was to investigate the influence of Lactobacillus plantarum LS/07 and inulin on the activity of β-glucuronidase enzyme, and counts of coliform and lactobacilli in fresh caecal digesta, cytokine levels (IL-6, IL-8), and trancription nuclear factor kappa beta (NFκB) activities in colon tissue and blood samples of rats with dextran sulphate sodium (DSS) induced acute colitis. The rats were randomly divided into four groups - CG, AC, AC+PRE and AC+PRO. Colitis was induced using of 5% DSS in drinking water for 7d. DSS application increased activity of β-glucuronidase (P < 0.001), increased counts of coliforms, and decreased lactobacilli counts (P < 0.05) in comparison to control group. Serum and tissue levels of IL-6 and IL-8 as well as tissue NFκB activities showed increased expression in acute colitis group. Inulin diet modified counts of microorganims and decreased β-glucuronidase activity, suppressed NFκB activities (P < 0.001) and down regulate synthesis of IL-6 (P < 0.01) in serum and colon tissue and tissue IL-8 (P < 0.05). Lactobacillus plantarum LS/07 decreased β-glucuronidase activity (P < 0.05), levels of IL-6 and IL-8 (P < 0.001). These results were consistent with the addition of histological findings. Our results indicate that dietary intake of Lactobacillus plantarum LS/07 and inulin suppressed expression observed markers, which play an important role in the inflammatory process, which predisposes their use in prevention or treatment of acute colitis.

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

    PubMed

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

    2013-02-14

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

  4. CD137 Facilitates the Resolution of Acute DSS-Induced Colonic Inflammation in Mice

    PubMed Central

    Martínez Gómez, Julia M.; Chen, Lieping; Schwarz, Herbert; Karrasch, Thomas

    2013-01-01

    Background CD137 and its ligand (CD137L) are potent immunoregulatory molecules that influence activation, proliferation, differentiation and cell death of leukocytes. Expression of CD137 is upregulated in the lamina propria cells of Crohn’s disease patients. Here, the role of CD137 in acute Dextran-Sodium-Sulfate (DSS)-induced colitis in mice was examined. Methods We induced acute large bowel inflammation (colitis) via DSS administration in CD137−/− and wild-type (WT) mice. Colitis severity was evaluated by clinical parameters (weight loss), cytokine secretion in colon segment cultures, and scoring of histological inflammatory parameters. Additionally, populations of lamina propria mononuclear cells (LPMNC) and intraepithelial lymphocytes (IEL) were characterized by flow cytometry. In a subset of mice, resolution of intestinal inflammation was evaluated 3 and 7 days after withdrawal of DSS. Results We found that both CD137−/− and WT mice demonstrated a similar degree of inflammation after 5 days of DSS exposure. However, the resolution of colonic inflammation was impaired in the absence of CD137. This was accompanied by a higher histological score of inflammation, and increased release of the pro-inflammatory mediators granulocyte macrophage colony-stimulating factor (GM-CSF), CXCL1, IL-17 and IFN-γ. Further, there were significantly more neutrophils among the LPMNC of CD137−/− mice, and reduced numbers of macrophages among the IEL. Conclusion We conclude that CD137 plays an essential role in the resolution of acute DSS-induced intestinal inflammation in mice. PMID:24023849

  5. Aponecrotic, antiangiogenic and antiproliferative effects of a novel dextran derivative on breast cancer growth in vitro and in vivo.

    PubMed

    Di Benedetto, Mélanie; Starzec, Anna; Colombo, Bruno M; Briane, Dominique; Perret, Gérard Y; Kraemer, Michel; Crépin, Michel

    2002-04-01

    1. Since the sodium phenylacetate (NaPa) was reported to enhance the inhibitory effect of carboxymethyl benzylamide dextran (CMDB) on the breast cancer growth, we performed the esterification of CMDB with NaPa to obtain a new drug carrying the characteristics of these two components. A new molecule, phenylacetate carboxymethyl benzylamide dextran, was named NaPaC. 2. We investigated in vitro and in vivo the effects of NaPaC on MCF-7ras cell growth as well as its apoptotic and antiangiogenic effects in comparison to NaPa and CMDB. In addition, we assessed in vitro the antiproliferative effects of these drugs on other breast cancer cells, including MDA-MB-231, MDA-MB-435 and MCF-7. 3. In vitro, NaPaC inhibited MCF-7ras cell proliferation by 40% at concentration lower than that of CMDB and NaPa (12 microM vs 73 microM and 10 mM). IC(50)s were 6 and 28 microM for NaPaC and CMDB, respectively. The similar results were obtained for three other breast cancer cell lines. NaPaC reduced the DNA replication and induced cell recruitment in G(0)/G(1) phase more efficiently than its components. Moreover, it induced a cell death at concentration 1000-fold lower than NaPa. 4. In vivo, CMDB (150 mg kg(-1)) and NaPa (40 mg kg(-1)) inhibited the MCF-7ras tumour growth by 37 and 57%, respectively, whereas NaPaC (15 mg kg(-1)) decreased tumour growth by 66% without toxicity. 5. NaPa or CMDB reduced the microvessel number in tumour by 50% after 7 weeks of treatment. NaPaC had the same effect after only 2 weeks. After 7 weeks, it generated a large necrosis area without detectable microvessels. In vitro, NaPaC inhibited human endothelial cell proliferation more efficiently than CMDB or NaPa. NaPaC interacts with vascular endothelial growth factor as observed by affinity electrophoresis. 6. NaPaC acts like NaPa and CMDB but in more potent manner than components used separately. Its antiproliferative, aponecrotic and anti-angiogenic actions make it a good candidate for a new anti

  6. Aponecrotic, antiangiogenic and antiproliferative effects of a novel dextran derivative on breast cancer growth in vitro and in vivo

    PubMed Central

    Benedetto, Mélanie Di; Starzec, Anna; Colombo, Bruno M; Briane, Dominique; Perret, Gérard Y; Kraemer, Michel; Crépin, Michel

    2002-01-01

    1 Since the sodium phenylacetate (NaPa) was reported to enhance the inhibitory effect of carboxymethyl benzylamide dextran (CMDB) on the breast cancer growth, we performed the esterification of CMDB with NaPa to obtain a new drug carrying the characteristics of these two components. A new molecule, phenylacetate carboxymethyl benzylamide dextran, was named NaPaC. We investigated in vitro and in vivo the effects of NaPaC on MCF-7ras cell growth as well as its apoptotic and antiangiogenic effects in comparison to NaPa and CMDB. In addition, we assessed in vitro the antiproliferative effects of these drugs on other breast cancer cells, including MDA-MB-231, MDA-MB-435 and MCF-7. In vitro, NaPaC inhibited MCF-7ras cell proliferation by 40% at concentration lower than that of CMDB and NaPa (12 μM vs 73 μM and 10 mM). IC50s were 6 and 28 μM for NaPaC and CMDB, respectively. The similar results were obtained for three other breast cancer cell lines. NaPaC reduced the DNA replication and induced cell recruitment in G0/G1 phase more efficiently than its components. Moreover, it induced a cell death at concentration 1000-fold lower than NaPa. In vivo, CMDB (150 mg kg−1) and NaPa (40 mg kg−1) inhibited the MCF-7ras tumour growth by 37 and 57%, respectively, whereas NaPaC (15 mg kg−1) decreased tumour growth by 66% without toxicity. NaPa or CMDB reduced the microvessel number in tumour by 50% after 7 weeks of treatment. NaPaC had the same effect after only 2 weeks. After 7 weeks, it generated a large necrosis area without detectable microvessels. In vitro, NaPaC inhibited human endothelial cell proliferation more efficiently than CMDB or NaPa. NaPaC interacts with vascular endothelial growth factor as observed by affinity electrophoresis. NaPaC acts like NaPa and CMDB but in more potent manner than components used separately. Its antiproliferative, aponecrotic and anti-angiogenic actions make it a good candidate for a new anti-cancer drug. PMID

  7. Low sodium level

    MedlinePlus

    Low sodium level is a condition in which the amount of sodium (salt) in the blood is lower than normal. The ... Sodium is found mostly in the body fluids outside the cells. It is very important for maintaining ...

  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. Novel magnetic nanoparticles coated by benzene- and β-cyclodextrin-bearing dextran, and the sorption of polycyclic aromatic hydrocarbon.

    PubMed

    Cho, Eunae; Tahir, Muhammad Nazir; Choi, Jae Min; Kim, Hwanhee; Yu, Jae-Hyuk; Jung, Seunho

    2015-11-20

    We present the synthesis of novel magnetic nanoparticles functionalized by benzene- and β-cyclodextrin-derivatized dextran. The grafting strategy was based on the [alkynyl-iron] cluster in the modified dextrans, which were prepared by click reaction from alkyne-modified dextran and benzyl azide or mono-6-O-deoxy-monoazido β-cyclodextrin. Characterization was then carried out by thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and vibrating sample magnetometry. Using the developed magnetic nanoparticles, the potential for removing polycyclic aromatic hydrocarbons such as phenanthrene and pyrene by sorption onto the nanomaterials was assessed. In the sorption, pi-stacking interactions of the benzene-derivatized dextran and host-guest chemistry of the β-cyclodextrin-derivatized dextran were considered to be significant. Furthermore, the polysaccharide derivative-coated magnetic adsorbents could be recovered by an external magnet for reuse. PMID:26344275

  10. Arginine as an eluent overcomes the hindrance of monoclonal antibody quantification by dextran sulfate in protein A affinity chromatography.

    PubMed

    Kim, Bong Gyun; Park, Hong Woo

    2015-01-01

    Analytical chromatography using protein A affinity columns was employed for the fast and simple quantitative analysis of monoclonal antibodies (mAb) from suspension cultures of recombinant Chinese hamster ovary (rCHO) cells. Reliable results could not be obtained from analysis of rCHO cell culture supernatants containing dextran sulfate using elution buffers such as phosphate, glycine, or MgCl2 . These problems increased as the number of analysis and the concentration of dextran sulfate in samples increased. Arginine was identified as an alternative eluent to overcome the hindrance by dextran sulfate. When the samples contain dextran sulfate up to 100 mg/L, the elution buffer containing 0.6-1.0 M arginine at pH 3.0-3.8 is useful for the effective analysis. Reproducible results in the mAb quantification could be obtained by this developed arginine elution buffer from rCHO cell culture supernatants containing dextran sulfate.

  11. Novel magnetic nanoparticles coated by benzene- and β-cyclodextrin-bearing dextran, and the sorption of polycyclic aromatic hydrocarbon.

    PubMed

    Cho, Eunae; Tahir, Muhammad Nazir; Choi, Jae Min; Kim, Hwanhee; Yu, Jae-Hyuk; Jung, Seunho

    2015-11-20

    We present the synthesis of novel magnetic nanoparticles functionalized by benzene- and β-cyclodextrin-derivatized dextran. The grafting strategy was based on the [alkynyl-iron] cluster in the modified dextrans, which were prepared by click reaction from alkyne-modified dextran and benzyl azide or mono-6-O-deoxy-monoazido β-cyclodextrin. Characterization was then carried out by thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and vibrating sample magnetometry. Using the developed magnetic nanoparticles, the potential for removing polycyclic aromatic hydrocarbons such as phenanthrene and pyrene by sorption onto the nanomaterials was assessed. In the sorption, pi-stacking interactions of the benzene-derivatized dextran and host-guest chemistry of the β-cyclodextrin-derivatized dextran were considered to be significant. Furthermore, the polysaccharide derivative-coated magnetic adsorbents could be recovered by an external magnet for reuse.

  12. Arginine as an eluent overcomes the hindrance of monoclonal antibody quantification by dextran sulfate in protein A affinity chromatography.

    PubMed

    Kim, Bong Gyun; Park, Hong Woo

    2015-01-01

    Analytical chromatography using protein A affinity columns was employed for the fast and simple quantitative analysis of monoclonal antibodies (mAb) from suspension cultures of recombinant Chinese hamster ovary (rCHO) cells. Reliable results could not be obtained from analysis of rCHO cell culture supernatants containing dextran sulfate using elution buffers such as phosphate, glycine, or MgCl2 . These problems increased as the number of analysis and the concentration of dextran sulfate in samples increased. Arginine was identified as an alternative eluent to overcome the hindrance by dextran sulfate. When the samples contain dextran sulfate up to 100 mg/L, the elution buffer containing 0.6-1.0 M arginine at pH 3.0-3.8 is useful for the effective analysis. Reproducible results in the mAb quantification could be obtained by this developed arginine elution buffer from rCHO cell culture supernatants containing dextran sulfate. PMID:26363185

  13. 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

  14. Low-density lipoprotein apheresis using the Liposorber dextran sulfate cellulose system for patients with hypercholesterolemia refractory to medical therapy.

    PubMed

    Gordon, B R; Saal, S D

    1996-01-01

    A subset of patients with familial hypercholesterolemia (FH) have an inadequate lipid-lowering response to diet and drug treatment and should be considered for low-density lipoprotein (LDL)-apheresis therapy. This procedure selectively removes apolipoprotein B-containing particles [LDL, very-low-density lipoprotein, lipoprotein(a)] from plasma independent of diet and drug therapy. Methods for performing LDL-apheresis include dextran sulfate cellulose adsorption, immunoadsorption, and heparin-induced extracorporeal precipitation. The Liposorber Study Group evaluated LDL removal using the Liposorber LA-15 LDL-apheresis System in 64 patients with FH who had not responded adequately to diet and maximal drug therapy. Mean acute reductions in LDL cholesterol (LDL-C) were 76% in heterozygous FH (HtFH) patients and 81% in homozygous FH (HoFH) patients. Time-averaged levels of LDL-C were lowered 41% in HtFH and 53% in HoFH patients. Hypotension was the most frequent side effect, occurring in 3% of procedures. The Liposorber LA-15 System has been approved by the Food and Drug Administration and is recommended for 1) patients with functional homozygous FH (LDL-C level > 500 mg/dL; 2) patients with coronary artery disease (CAD) and LDL-C levels > or = 200 mg/dL; 3) patients without CAD, but an LDL-C level > or = 300 mg/dL. PMID:8915816

  15. Synthesis and characterization of Schiff base contained dextran microgels in water-in-oil inverse microemulsion.

    PubMed

    Su, Hongying; Jia, Qingming; Shan, Shaoyun

    2016-11-01

    Polysaccharide-based microgels with high water content, excellent biocompatibility and controllable particle size have been widely studied as ideal candidates for drug release and delivery. In this study, microgels based on dextran were developed via the Schiff base formation between aldehyded dextran and ethylenediamine in a water-in-oil (W/O) microemulsion. Particle size of the resulted microgel was controllable between 800 and 1100nm by modulating the amount of the employed co-surfactants (Span 80/Tween 80). Furthermore, fluoresceins (e.g., aminofluorescein) and drugs (e.g., doxorubicin) with free amino groups can be conjugated onto the network of the dextran-based microgel via Schiff base linkages. Since the Schiff base linkages are degradable via hydrolysis and their stability decreases with the environmental pH decreases, the resulted Schiff bases contained microgel showed a pH dependent degradation profile. These results indicated that the pH-sensitive microgel based on dextran could be used as promising drug delivery systems for biomedical applications.

  16. Size-Dependent Diffusion of Dextrans in Excised Porcine Corneal Stroma.

    PubMed

    Rajapakshal, Ajith; Fink, Michael; Todd, Brian A

    2015-09-01

    Delivery of therapeutic agents to the eye requires efficient transport through cellular and extracellular barriers. We evaluated the rate of diffusive transport in excised porcine corneal stroma using fluorescently labeled dextran molecules with hydrodynamic radii ranging from 1.3 to 34 nm. Fluorescence correlation spectroscopy (FCS) was used to measure diffusion coefficients of dextran molecules in the excised porcine corneal stroma. The preferential sensitivity of FCS to diffusion along two dimensions was used to differentially probe diffusion along the directions parallel to and perpendicular to the collagen lamellae of the corneal stroma. In order to develop an understanding of how size affects diffusion in cornea, diffusion coefficients in cornea were compared to diffusion coefficients measured in a simple buffer solution. Dextran molecules diffuse more slowly in cornea as compared to buffer solution. The reduction in diffusion coefficient is modest however (67% smaller), and is uniform over the range of sizes that we measured. This indicates that, for dextrans in the 1.3 to 34 nm range, the diffusion landscape of corneal stroma can be represented as a simple liquid with a viscosity approximately 1.5 times that of water. Diffusion coefficients measured parallel vs. perpendicular to the collagen lamellae were indistinguishable. This indicates that diffusion in the corneal stroma is not highly anisotropic. Our results support the notion that the corneal stroma is highly permeable and isotropic to transport of hydrophilic molecules and particles with hydrodynamic radii up to at least 34 nm.

  17. Micelles and polymersomes obtained by self-assembly of dextran and polystyrene based block copolymers.

    PubMed

    Houga, Clément; Giermanska, Joanna; Lecommandoux, Sébastien; Borsali, Redouane; Taton, Daniel; Gnanou, Yves; Le Meins, Jean-François

    2009-01-12

    The self-assembly of dextran-block-polystyrene (dex-b-PS) block copolymers was investigated in solution. The hydrophobic PS weight fraction in these block copolymers ranges from 7 to 92% w/w, whereas the average number molar mass of dextran was kept constant at 6600 gmol(-1). Self-assembly by direct dissolution in water could be performed only for block copolymers with a low hydrophobic content (7% w/w), whereas mixtures of tetrahydrofuran and dimethylsulfoxide were required for higher PS content, before transferring the structures into water. Core-shell micelles, ovoïds, and vesicles could be identified upon characterization by light and neutrons scattering, atomic force microscopy, and transmission electron microscopy. Most of the morphologies observed were not expected considering the chemical composition of the block copolymers. Finally, the size and shape of these nanoparticles were fixed upon cross-linking the dextran block through reaction of the hydroxyl groups with divinylsulfone. The role of the dextran conformation on the self-assembly process is discussed.

  18. Lowering of plasma cholesterol in herbivores and omnivores by low molecular weight dextran.

    PubMed

    Adam, O; Krejci, K

    1989-01-01

    Two rabbits and two home pigs were infused in a cross-over design with equal volumes, adapted to the plasma volumes of the animals, of dextran-40 and saline. The infusions resulted in a reduction of plasma cholesterol and control parameters, such as plasma protein, hemoglobin, and hematocrit. The reduction of hemoglobin and hematocrit was related to plasma expansion with both infusion regimens. With dextran-40 infusions the reduction of plasma protein was greater than hemodilution in both species (-18% in rabbits and -20% in home pigs), because of steric exclusion of the protein. Lowering of plasma cholesterol in rabbits was comparable to the reduction in plasma protein, whereas in home pigs the reduction of plasma cholesterol (-25%) surpassed that of plasma protein. Reports in the literature have shown that dextran infusions increase cholesterol concentration in liver cells, leading to a reduction of intestinal cholesterol resorption in omnivores. This dextran effect is supposed to be responsible for the observed additional reduction of plasma cholesterol levels in omnivores.

  19. Phospholipid-Dextran with a Single Coupling Point: a Useful Amphiphile for Functionalization of Nanomaterials

    PubMed Central

    Goodwin, Andrew P.; Tabakman, Scott M.; Welsher, Kevin; Sherlock, Sarah P.; Prencipe, Giuseppe; Dai, Hongjie

    2010-01-01

    Nanomaterials hold much promise for biological applications, but they require appropriate functionalization to provide biocompatibility in biological environments. For non-covalent functionalization with biocompatible polymers, the polymer must also remain attached to the nanomaterial after removal of its excess to mimic the high dilution conditions of administration in vivo. Reported here are the synthesis and utilization singly-substituted conjugates of dextran and a phospholipid (Dextran-DSPE) as stable coatings for nanomaterials. Suspensions of single walled carbon nanotubes were found not only to be stable to phosphate buffered saline (PBS), serum, and a variety of pH’s after excess polymer removal, but also provide brighter photoluminescence than carbon nanotubes suspended by poly(ethylene glycol)-DSPE. In addition, both gold nanoparticles (AuNPs) and gold nanorods (AuNRs) were found to maintain their dispersion and characteristic optical absorbance after transfer into Dextran-DSPE, and were obtained in much better yield than similar suspensions with PEG-phospholipid and commonly used thiol-PEG. These suspensions were also stable to PBS, serum, and a variety of pH’s after removal of excess polymer. Dextran-DSPE thus shows great promise as a general surfactant material for the functionalization of a variety of nanomaterials, which could facilitate future biological applications. PMID:19061329

  20. 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

    2015-06-01

    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. PMID:25843855

  1. Synthesis and characterization of Schiff base contained dextran microgels in water-in-oil inverse microemulsion.

    PubMed

    Su, Hongying; Jia, Qingming; Shan, Shaoyun

    2016-11-01

    Polysaccharide-based microgels with high water content, excellent biocompatibility and controllable particle size have been widely studied as ideal candidates for drug release and delivery. In this study, microgels based on dextran were developed via the Schiff base formation between aldehyded dextran and ethylenediamine in a water-in-oil (W/O) microemulsion. Particle size of the resulted microgel was controllable between 800 and 1100nm by modulating the amount of the employed co-surfactants (Span 80/Tween 80). Furthermore, fluoresceins (e.g., aminofluorescein) and drugs (e.g., doxorubicin) with free amino groups can be conjugated onto the network of the dextran-based microgel via Schiff base linkages. Since the Schiff base linkages are degradable via hydrolysis and their stability decreases with the environmental pH decreases, the resulted Schiff bases contained microgel showed a pH dependent degradation profile. These results indicated that the pH-sensitive microgel based on dextran could be used as promising drug delivery systems for biomedical applications. PMID:27516260

  2. Evaluating the Safety and Efficacy of Sodium-Restricted/Dietary Approaches to Stop Hypertension Diet After Acute Decompensated Heart Failure Hospitalization: Design and Rationale for the Geriatric OUt of hospital Randomized MEal Trial in Heart Failure (GOURMET-HF)

    PubMed Central

    Wessler, Jeffrey D.; Maurer, Mathew S.; Hummel, Scott S.

    2015-01-01

    Background Heart Failure (HF) is a major public health problem affecting predominantly older adults. Non-adherence to diet remains a significant contributor to acute decompensated HF (ADHF). The sodium-restricted Dietary Approaches to Stop Hypertension (DASH/SRD) eating plan reduces cardiovascular dysfunction that can lead to ADHF and is consistent with current HF guidelines. We propose that an intervention that promotes adherence to the DASH/SRD by home-delivering meals will be safe and improve health-related quality of life (QOL) in older adults following hospitalization for ADHF. Methods/Design This is a three center, randomized, single-blind, controlled trial of 12 weeks duration designed to determine the safety and efficacy of home-delivered DASH/SRD-compliant meals in older adults following discharge from ADHF hospitalization. 66 subjects will be randomized in a 1:1 stratified fashion by gender and left ventricular ejection fraction (< vs. ≥50%). Study subjects will receive either pre-prepared, home-delivered DASH/SRD-compliant meals or usual dietary advice for 4 weeks after hospital discharge. Investigators will be blinded to group assignment, food diaries, and urinary electrolyte measurements until study completion. The primary efficacy endpoint is the change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary scores for health-related QOL from study enrollment to 4 weeks post-discharge. Safety evaluation will focus on hypotension, renal insufficiency, and hyperkalemia. Exploratory endpoints include echocardiography, non-invasive vascular testing, markers of oxidative stress, and salt taste sensitivity. Conclusion This randomized controlled trial will test the efficacy, feasibility and safety of 4 weeks of DASH/SRD after ADHF hospitalization. By testing a novel dietary intervention supported by multiple levels of evidence including preliminary data in outpatients with stable HF, we will address a critical evidence gap in the care of older

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

    PubMed

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

    2015-10-15

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

  4. Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis

    PubMed Central

    Zheng, Zengjie; Jiang, Hailong; Huang, Yan; Wang, Jie; Qiu, Lei; Hu, Zhenlin; Ma, Xingyuan; Lu, Yiming

    2016-01-01

    Snake has been used for centuries as a traditional Chinese medicine, especially for therapeutic treatment for inflammatory diseases; however, its mechanisms of action and active constituents remain controversial. In our study, a tumor necrosis factor receptor 1 (TNFR1) selective binding peptide, Hydrostatin-SN1 (H-SN1), which was screened from a Hydrophis cyanocinctus venom gland T7 phage display library, was shown to exhibit significant anti-inflammatory activity in vitro and in vivo. As a TNFR1 antagonist, it reduced cytotoxicity mediated by TNF-α in L929 fibroblasts and effectively inhibited the combination between TNF-α with TNFR1 in surface plasmon resonance analysis. H-SN1 was also shown to suppress TNFR1–associated signaling pathways as it minimized TNF-α-induced NF-кB and MAPK activation in HEK293 embryonic kidney and HT29 adenocarcinoma cell lines. We next determined the effect of H-SN1 in vivo using a murine model of acute colitis induced by dextran sodium sulfate, demonstrating that H-SN1 lowered the clinical parameters of acute colitis including the disease activity index and histologic scores. H-SN1 also inhibited TNF/TNFR1 downstream targets at both mRNA and protein levels. These results indicate that H-SN1 might represent a suitable candidate for use in the treatment of TNF-α-associated inflammatory diseases such as inflammatory bowel diseases. PMID:27158082

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

    PubMed

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

    2015-10-01

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

  6. Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice.

    PubMed

    Qian, Zhengjiang; Wu, Zhiqin; Huang, Lian; Qiu, Huiling; Wang, Liyan; Li, Li; Yao, Lijun; Kang, Kang; Qu, Junle; Wu, Yonghou; Luo, Jun; Liu, Johnson J; Yang, Yi; Yang, Wancai; Gou, Deming

    2015-11-30

    Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2(-/-) mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6. Particularly, a dose-dependent inhibition on LPS-induced inflammatory responses was observed following treatment with MBF dichloromethane extract (MBF-DE), in which linoleic acid and ethyl linolenate were identified as two active compounds. Moreover, we elucidated that MBF-DE attenuated LPS-induced inflammatory responses by blocking activation of both NF-κB/p65 and pERK/MAPK pathways. In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage. In addition, MBF-fed MUC2(-/-) mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group. Overall, our results demonstrated that MBF suppressed the development of intestinal inflammation and tumorgenesis both in vitro and in vivo, and supports the potential of MBF as a therapeutic functional food for testing in human clinical trials.

  7. Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice

    PubMed Central

    Qian, Zhengjiang; Wu, Zhiqin; Huang, Lian; Qiu, Huiling; Wang, Liyan; Li, Li; Yao, Lijun; Kang, Kang; Qu, Junle; Wu, Yonghou; Luo, Jun; Liu, Johnson J.; Yang, Yi; Yang, Wancai; Gou, Deming

    2015-01-01

    Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2−/− mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6. Particularly, a dose-dependent inhibition on LPS-induced inflammatory responses was observed following treatment with MBF dichloromethane extract (MBF-DE), in which linoleic acid and ethyl linolenate were identified as two active compounds. Moreover, we elucidated that MBF-DE attenuated LPS-induced inflammatory responses by blocking activation of both NF-κB/p65 and pERK/MAPK pathways. In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage. In addition, MBF-fed MUC2−/− mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group. Overall, our results demonstrated that MBF suppressed the development of intestinal inflammation and tumorgenesis both in vitro and in vivo, and supports the potential of MBF as a therapeutic functional food for testing in human clinical trials. PMID:26615818

  8. Danaparoid sodium.

    PubMed

    Acostamadiedo, J M; Iyer, U G; Owen, J

    2000-05-01

    Danaparoid sodium (Orgaran, Organon) is a heparinoid glycosamino-glycuronan antithrombotic agent approved for the prophylaxis of post-operative deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing elective hip replacement surgery. Danaparoid is a low molecular weight heparinoid consisting of a mixture of heparan sulphate (84%), dermatan sulphate (12%) and small amounts of chondroitin sulphate (4%), whose antithrombotic activity has been well established. Its pharmacological effect is exerted primarily by inhibiting Factors Xa (FXa) and IIa (FIIa) at a ratio greater than heparin, with a minimal effect on platelet function. Danaparoid exhibits low cross-reactivity with heparin-induced antibodies when compared with heparin or low molecular weight heparins (LMWH), thereby making it an excellent choice for the management of heparin-induced thrombocytopenia (HIT). It has excellent bioavailability following s.c. injection. Danaparoid has little effect on routine coagulation tests (activated partial thromboplastin time [aPTT], prothrombin time [PT], and thrombin time [TT]). Patients with elevated serum creatinine should be monitored carefully. For its FDA approved indication (DVT prophylaxis during hip replacement surgery), its cost per day is approximately eight times more than LMWH. Even though monitoring is not routinely necessary according to the manufacturer for its approved indication, monitoring is frequently necessary when it is used in other clinical scenarios. Its higher cost than comparable therapies for DVT prophylaxis and the low availability of the FXa assay in most non-tertiary care hospitals has limited the widespread use of danaparoid. Danaparoid has been found to be effective in the treatment of HIT although this is an off label use, despite being the most frequent reason why danaparoid is used. PMID:11249517

  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. Nedocromil sodium (Tilade).

    PubMed

    Bartels, L A; Farrington, E

    1994-01-01

    Nedocromil sodium is a well-tolerated antiasthmatic agent for initial therapy in patients with mild or moderate asthma not well controlled with inhaled beta-2 agonists and/or where methylxanthines are indicated. Like cromolyn sodium, nedocromil sodium offers a potential alternative to inhaled corticosteroids as maintenance therapy in patients with mild or moderate asthma not adequately controlled by bronchodilators. Furthermore, cromolyn sodium and nedocromil sodium may also reduce the usage of corticosteroids and provide some additional symptom control in patients whose asthma is not suitably controlled by optimal doses of inhaled corticosteroids. Both nedocromil sodium and cromolyn sodium are more efficacious than placebo for controlling of asthma, however, few studies have compared the effectiveness of cromolyn versus nedocromil at this time. Further experience and comparison studies of nedocromil sodium with cromolyn sodium in children are required before the role of nedocromil sodium as maintenance treatment in young asthmatic patients can be defined.

  11. Genotoxic effects of sodium arsenite and sodium arsenate after chronic exposure of Drosophila melanogaster larvae

    SciTech Connect

    Ramos-Morales, P.; Ordaz, M.G.; Munoz, A.

    1995-11-01

    Two arsenic compounds, namely: NaAsO{sub 2} (Sodium Arsenite) and Na{sub 2}HAsO{sub 4} (Sodium Arsenate) were tested for its chronic effect in somatic cells of Drosophila melanogaster. In a previous study in Drosophila we found that both compounds induced SLRL mutations, but failed to induce sex chromosome loss. In the SMART, after acute exposure, only sodium arsenite was positive when cells of the wings were used; however, both were positives in cells of the eyes of Drosophila. The genotoxicity of both compounds localized mainly on somatic cells, in agreement with reports on the carcinogenicity potential of arsenical compounds. The Somatic mutation and recombination test (SMART) was run employing cells of the wing imaginal discs from flr{sup 3}/mwh larvae. First instar larvae (24 {plus_minus} 4 h) were treated during 96 hours with sodium arsenite [0.015-4.0 ppm], and sodium arsenate [0.2-10 ppm], negative control was treated with distilled water. The frequency of spots by wing induced by the two arsenic salts were compared with control according with Frei and Wuergler procedure. Data show that sodium arsenite tested negative at all concentrations, but sodium arsenate tested positive at 0.8, 2 and 10 ppm (P<0.05). This results were consistent with the co-mutagenic role of sodium arsenite, but show that sodium arsenate was mutagenic in Drosophila test system under chronic exposure.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. Promoting inflammatory lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) aggravated intestinal inflammation in mice with experimental acute colitis

    PubMed Central

    Wang, X.L.; Zhao, J.; Qin, L.; Qiao, M.

    2016-01-01

    Angiogenesis and lymphangiogenesis are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, it is not understood if inflammatory lymphangiogenesis is a pathological consequence or a productive attempt to resolve the inflammation. This study investigated the effect of lymphangiogenesis on intestinal inflammation by overexpressing a lymphangiogenesis factor, vascular endothelial growth factor-C (VEGF-C), in a mouse model of acute colitis. Forty eight-week-old female C57BL/6 mice were treated with recombinant adenovirus overexpressing VEGF-C or with recombinant VEGF-C156S protein. Acute colitis was then established by exposing the mice to 5% dextran sodium sulfate (DSS) for 7 days. Mice were evaluated for disease activity index (DAI), colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), and VEGFR-3mRNA expression in colon tissue. When acute colitis was induced in mice overexpressing VEGF-C, there was a significant increase in colonic epithelial damage, inflammatory edema, microvessel density, and neutrophil infiltration compared to control mice. These mice also exhibited increased lymphatic vessel density (73.0±3.9 vs 38.2±1.9, P<0.001) and lymphatic vessel size (1974.6±104.3 vs 1639.0±91.5, P<0.001) compared to control mice. Additionally, the expression of VEGFR-3 mRNA was significantly upregulated in VEGF-C156S mice compared to DSS-treated mice after induction of colitis (42.0±1.4 vs 3.5±0.4, P<0.001). Stimulation of lymphangiogenesis by VEGF-C during acute colitis promoted inflammatory lymphangiogenesis in the colon and aggravated intestinal inflammation. Inflammatory lymphangiogenesis may have pleiotropic effects at different stages of IBD. PMID:27074165

  14. Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

    PubMed Central

    Amiel, Catherine; Duroux, Laurent; Larsen, Kim Lambertsen; Städe, Lars Wagner; Wimmer, Reinhard; Wintgens, Véronique

    2015-01-01

    Summary Novel (S)-camptothecin–dextran polymers were obtained by “click” grafting of azide-modified (S)-camptothecin and alkyne-modified dextrans. Two series based on 10 kDa and 70 kDa dextrans were prepared with a degree of substitution of (S)-camptothecin between 3.1 and 10.2%. The binding properties with β-cyclodextrin and β-cyclodextrin polymers were measured by isothermal titration calorimetry and fluorescence spectroscopy, showing no binding with β-cyclodextrin but high binding with β-cyclodextrin polymers. In aqueous solution nanoparticles were formed from association between the (S)-camptothecin–dextran polymers and the β-cyclodextrin polymers. PMID:25670998

  15. Wound-dressing materials with antibacterial activity from electrospun polyurethane-dextran nanofiber mats containing ciprofloxacin HCl.

    PubMed

    Unnithan, Afeesh R; Barakat, Nasser A M; Pichiah, P B Tirupathi; Gnanasekaran, Gopalsamy; Nirmala, R; Cha, Youn-Soo; Jung, Che-Hun; El-Newehy, Mohamed; Kim, Hak Yong

    2012-11-01

    Dextran is a versatile biomacromolecule for preparing electrospun nanofibrous membranes by blending with either water-soluble bioactive agents or hydrophobic biodegradable polymers for biomedical applications. In this study, an antibacterial electrospun scaffold was prepared by electrospinning of a solution composed of dextran, polyurethane (PU) and ciprofloxacin HCl (CipHCl) drug. The obtained nanofiber mats have good morphology. The mats were characterized by various analytical techniques. The interaction parameters between fibroblasts and the PU-dextran and PU-dextran-drug scaffolds such as viability, proliferation, and attachment were investigated. The results indicated that the cells interacted favorably with the scaffolds especially the drug-containing one. Moreover, the composite mat showed good bactericidal activity against both of Gram-positive and Gram-negative bacteria. Overall, our results conclude that the introduced scaffold might be an ideal biomaterial for wound dressing applications.

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

    PubMed Central

    Nagy-Szakal, Dorottya; Mir, Sabina A. V.; Harris, R. Alan; Dowd, Scot E.; Yamada, Takeshi; Lacorazza, H. Daniel; Tatevian, Nina; Smith, C. Wayne; de Zoeten, Edwin F.; Klein, John; Kellermayer, Richard

    2015-01-01

    Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases (IBDs): Crohn disease (CD) and ulcerative colitis (UC). Dietary n-6 fatty acids have been associated with UC in prospective studies. However, the critical developmental period when (n-6) consumption may induce UC is not known. We examined the effects of transiently increased n-6 consumption during pediatric development on subsequent dextran-sulfate-sodium (DSS)-induced acute murine colitis. The animals transiently became obese then rapidly lost this phenotype. Interestingly, mice were protected against DSS colitis 40 days after n-6 consumption. The transient high n-6-induced protection against colitis was fat type- and dietary reversal-dependent and could be transferred to germ-free mice by fecal microbiota transplantation. We also detected decreased numbers of chemokine receptor (Cxcr)5+ CD4+ T cells in the mesenteric lymph nodes (MLNs) of transiently n-6-fed mice. Further experiments revealed that anti-chemokine ligand (Cxcl)13 (the ligand of Cxcr5) antibody treatment decreased DSS colitis severity, implicating the importance of the Cxcr5-Cxcl13 pathway in mammalian colitis. Consecutively, we found elevated CXCL13 concentrations (CD: 1.8-fold, P = 0.0077; UC: 1.9-fold, P = 0.056) in the serum of untreated pediatric IBD patients. The human serologic observations supported the translational relevance of our findings.—Nagy-Szakal, D., Mir, S. A. V., Harris, R. A., Dowd, S. E., Yamada, T., Lacorazza, H. D., Tatevian, N., Smith, C. W., de Zoeten, E. F., Klein, J., Kellermayer, R. Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis. PMID:25903104

  17. Absence of stearoyl-CoA desaturase-1 does not promote DSS-induced acute colitis

    PubMed Central

    MacDonald, Marcia L.E.; Bissada, Nagat; Vallance, Bruce A.; Hayden, Michael R.

    2009-01-01

    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. PMID:19695343

  18. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  19. The effects of synthesis method on the physical and chemical properties of dextran coated iron oxide nanoparticles

    PubMed Central

    Hauser, Anastasia K.; Mathias, Ronita; Anderson, Kimberly W.; Hilt, J. Zach

    2015-01-01

    Iron oxide nanoparticles coated with dextran were synthesized via four variations on the co-precipitation method. The methods ranged from in situ formation of the nanoparticles within the dextran solution to the adsorption of dextran to the nanoparticle surface following nucleation and extensive washing. The timing of the addition of dextran into the reaction mixture was found to greatly influence the physical and chemical properties of the magnetic nanoparticles. Batches of dextran coated iron oxide nanoparticles were synthesized by each method in triplicate, and the nanoparticles were further crosslinked with epichlorohydrin. The properties of the nanoparticles such as size, percentage of dextran coating, stability in solution, crystallinity, and magnetic properties were evaluated. The simultaneous semi-two-step method injected the reducing agent and the dextran solution into the reaction vessel at the same time. This method resulted in the greatest batch-to-batch reproducibility of nanoparticle properties and the least variation in nanoparticles synthesized in the same batch. The two-step method resulted in the greatest variation of the characteristics examined between batches. The one-step method was synthesized with both five grams and one gram of dextran to investigate the effects of solution viscosity on the resulting nanoparticle characteristics. The one-step method with five grams of dextran resulted in nanoparticles with significantly smaller crystal sizes (5.4 ± 1.9 nm) and lower specific adsorption rate (SAR) values (138.4 ± 13.6 W/g) in an alternating magnetic field (58 kA/m, 292 kHz). However, this method resulted in nanoparticles that were very stable in PBS over 12 hours, which is most likely due to the greater dextran coating (60.0 ± 2.7 weight percent). For comparison, the simultaneous semi-two-step method generated nanoparticles 179.2 ± 18.3 nm in diameter (crystal size 12.1 ± 0.2 nm) containing 18.3 ± 1.2 weight percent dextran with a SAR

  20. Experimental study of the efficiency of oxidized dextran for prevention of influenza A/H5N1.

    PubMed

    Shkurupy, V A; Potapova, O V; Sharkova, T V; Troitskii, A V; Gulyaeva, E P; Bystrova, T N; Shestopalov, A M

    2014-11-01

    Oxidized dextran is suggested for prevention of infection induced by influenza A/H5N1 viruses, methods of its use and doses are determined. Two intravenous injections of dextran 3 and 1 days before experimental infection of outbred mice by influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus resulted in a high preventive dose-dependent effect: the mean lifespan was 25% prolonged, the mortality decreased 3-fold. PMID:25403410

  1. Hemodynamic and regional blood flow distribution responses to dextran, hydralazine, isoproterenol and amrinone during experimental cardiac tamponade

    SciTech Connect

    Millard, R.W.; Fowler, N.O.; Gabel, M.

    1983-06-01

    Four different interventions were examined in dogs with cardiac tamponade. Infusion of 216 to 288 ml saline solution into the pericardium reduced cardiac output from 3.5 +/- 0.3 to 1.7 +/- 0.2 liters/min as systemic vascular resistance increased from 4,110 +/- 281 to 6,370 +/- 424 dynes . s . cm-5. Left ventricular epicardial and endocardial blood flows were 178 +/- 13 and 220 +/- 12 ml/min per 100 g, respectively, and decreased to 72 +/- 14 and 78 +/- 11 ml/min per 100 g with tamponade. Reductions of 25 to 65% occurred in visceral and brain blood flows and in a composite brain sample. Cardiac output during tamponade was significantly increased by isoproterenol, 0.5 microgram/kg per min intravenously; hydralazine, 40 mg intravenously; dextran infusion or combined hydralazine and dextran, but not by amrinone. Total systemic vascular resistance was reduced by all interventions. Left ventricular epicardial flow was increased by isoproterenol, hydralazine and the hydralazine-dextran combination. Endocardial flow was increased by amrinone and the combination of hydralazine and dextran. Right ventricular myocardial blood flow increased with all interventions except dextran. Kidney cortical and composite brain blood flows were increased by both dextran alone and by the hydralazine-dextran combinations. Blood flow to small intestine was increased by all interventions as was that to large intestine by all except amrinone and hydralazine. Liver blood flow response was variable. The most pronounced hemodynamic and tissue perfusion improvements during cardiac tamponade were effected by combined vasodilation-blood volume expansion with a hydralazine-dextran combination. Isoproterenol had as dramatic an effect but it was short-lived. Amrinone was the least effective intervention.

  2. Heparin cofactor II is degraded by heparan sulfate and dextran sulfate.

    PubMed

    Saito, Akio

    2015-02-20

    Heparan sulfate normally binds to heparin cofactor II and modulates the coagulation pathway by inhibiting thrombin. However, when human heparin cofactor II was incubated with heparan sulfate, heparin cofactor II became degraded. Other glycosaminoglycans were tested, including hyaluronic acid, chondroitin sulfates, dermatan sulfate, and heparin, but only dextran sulfate also degraded heparin cofactor II. Pretreatment of heparan sulfate with heparinase reduced its heparin cofactor II-degrading activity. Heparan sulfate and dextran sulfate diminished the thrombin inhibitory activity of heparin cofactor II. Other serpins, including antithrombin III and pigment epithelium-derived factor, were also degraded by heparan sulfate. This is the first evidence of acidic polysaccharides exhibiting protein-degrading activity without the aid of other proteins.

  3. Quantitation of uveoscleral outflow in normotensive and glaucomatous Beagles by /sup 3/H-labeled dextran

    SciTech Connect

    Barrie, K.P.; Gum, G.G.; Samuelson, D.A.; Gelatt, K.N.

    1985-01-01

    In uveoscleral outflow, aqueous humor leaves the anterior chamber and passes caudally through the trabecular meshwork and the sclerociliary cleft to enter the supraciliary and suprachoroidal spaces. The fluid is then absorbed by choroidal and scleral circulations. Using /sup 3/H-labeled dextran, uveoscleral outflow was quantitated in normotensive and glaucomatous Beagles under general anesthesia. The intrascleral plexus was isolated and /sup 3/H-labeled dextran was injected into the anterior chamber. Intrascleral plexus contents were sampled every 5 minutes over a 30- to 60-minute period. The eyes were enucleated, sectioned, and prepared for scintillation counting. Uveoscleral outflow accounted for 15% and 3% of the total aqueous humor outflow in the normotensive dogs and in the advanced glaucomatous dogs, respectively. In the advanced glaucomatous Beagle, conventional and uveoscleral outflow pathways were reduced and contributed to the etiopathogenesis of glaucoma.

  4. Dextran-gated, multifunctional mesoporous nanoparticle for glucose-responsive and targeted drug delivery.

    PubMed

    Sinha, Arjyabaran; Chakraborty, Atanu; Jana, Nikhil R

    2014-12-24

    Design of drug delivery nanocarrier having targeted recognition followed by bioresponsive controlled release, especially via glucose-responsive release, is a challenging issue. Here, we report magnetic mesoporous silica (MMS)-based drug delivery nanocarrier that can target specific cell and release drug via glucose-responsive gate. The design involves synthesis of MMS functionalized with phenylboronic acid and folate. After drug loading inside the pores of MMS, outside of the pores are closed by dextran via binding with phenylboronic acid. Dextran-gated pores are opened for drug release in the presence of glucose that competes binding with phenylboronic acid. We found that tolbutamide and camptothecin loaded MMS can target beta cells and cancer cells, respectively, release drugs depending on bulk glucose concentration and offers glucose concentration dependent cytotoxicity. Developed functional MMS can be used for advanced drug delivery applications for diabetes and cancers with more efficient therapy. PMID:25458145

  5. Reducing the Oxidation Level of Dextran Aldehyde in a Chitosan/Dextran-Based Surgical Hydrogel Increases Biocompatibility and Decreases Antimicrobial Efficacy.

    PubMed

    Chan, Maggie; Brooks, Heather J L; Moratti, Stephen C; Hanton, Lyall R; Cabral, Jaydee D

    2015-06-16

    A highly oxidized form of a chitosan/dextran-based hydrogel (CD-100) containing 80% oxidized dextran aldehyde (DA-100) was developed as a post-operative aid, and found to significantly prevent adhesion formation in endoscopic sinus surgery (ESS). However, the CD-100 hydrogel showed moderate in vitro cytotoxicity to mammalian cell lines, with the DA-100 found to be the cytotoxic component. In order to extend the use of the hydrogel to abdominal surgeries, reformulation using a lower oxidized DA (DA-25) was pursued. The aim of the present study was to compare the antimicrobial efficacy, in vitro biocompatibility and wound healing capacity of the highly oxidized CD-100 hydrogel with the CD-25 hydrogel. Antimicrobial studies were performed against a range of clinically relevant abdominal microorganisms using the micro-broth dilution method. Biocompatibility testing using human dermal fibroblasts was assessed via a tetrazolium reduction assay (MTT) and a wound healing model. In contrast to the original DA-100 formulation, DA-25 was found to be non-cytotoxic, and showed no overall impairment of cell migration, with wound closure occurring at 72 h. However, the lower oxidation level negatively affected the antimicrobial efficacy of the hydrogel (CD-25). Although the CD-25 hydrogel's antimicrobial efficacy and anti-fibroblast activity is decreased when compared to the original CD-100 hydrogel formulation, previous in vivo studies show that the CD-25 hydrogel remains an effective, biocompatible barrier agent in the prevention of postoperative adhesions.

  6. Reducing the Oxidation Level of Dextran Aldehyde in a Chitosan/Dextran-Based Surgical Hydrogel Increases Biocompatibility and Decreases Antimicrobial Efficacy

    PubMed Central

    Chan, Maggie; Brooks, Heather J. L.; Moratti, Stephen C.; Hanton, Lyall R.; Cabral, Jaydee D.

    2015-01-01

    A highly oxidized form of a chitosan/dextran-based hydrogel (CD-100) containing 80% oxidized dextran aldehyde (DA-100) was developed as a post-operative aid, and found to significantly prevent adhesion formation in endoscopic sinus surgery (ESS). However, the CD-100 hydrogel showed moderate in vitro cytotoxicity to mammalian cell lines, with the DA-100 found to be the cytotoxic component. In order to extend the use of the hydrogel to abdominal surgeries, reformulation using a lower oxidized DA (DA-25) was pursued. The aim of the present study was to compare the antimicrobial efficacy, in vitro biocompatibility and wound healing capacity of the highly oxidized CD-100 hydrogel with the CD-25 hydrogel. Antimicrobial studies were performed against a range of clinically relevant abdominal microorganisms using the micro-broth dilution method. Biocompatibility testing using human dermal fibroblasts was assessed via a tetrazolium reduction assay (MTT) and a wound healing model. In contrast to the original DA-100 formulation, DA-25 was found to be non-cytotoxic, and showed no overall impairment of cell migration, with wound closure occurring at 72 h. However, the lower oxidation level negatively affected the antimicrobial efficacy of the hydrogel (CD-25). Although the CD-25 hydrogel’s antimicrobial efficacy and anti-fibroblast activity is decreased when compared to the original CD-100 hydrogel formulation, previous in vivo studies show that the CD-25 hydrogel remains an effective, biocompatible barrier agent in the prevention of postoperative adhesions. PMID:26086827

  7. 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. PMID:27455406

  8. Fluorescence tomographic imaging of sentinel lymph node using near-infrared emitting bioreducible dextran nanogels.

    PubMed

    Li, Jiejing; Jiang, Beiqi; Lin, Chao; Zhuang, Zhigang

    2014-01-01

    Sentinel lymph node (SLN) mapping is a critical procedure for SLN biopsy and its diagnosis as tumor metastasis in clinical practice. However, SLN mapping agents used in the clinic frequently cause side effects and complications in the patients. Here, we report the development of a near-infrared (NIR) emitting polymeric nanogel with hydrodynamic diameter of ~28 nm - which is the optimal size for SLN uptake - for noninvasive fluorescence mapping of SLN in a mouse. This polymeric nanogel was obtained by coupling Cy7, an NIR dye, to the self-assembled nanogel from disulfide-linked dextran-deoxycholic acid conjugate with the dextran of 10 kDa, denoted as Dex-Cy7. Fluorescence imaging analysis showed that Dex-Cy7 nanogels had an enhanced photostability when compared to Cy7 alone. After intradermal injection of Dex-Cy7 nanogel into the front paw of a mouse, the nanogels were able to migrate into the mouse's axillary lymph node, exhibiting longer retention time and higher fluorescence intensity in the node when compared to Cy7 alone. An immunohistofluorescence assay revealed that the nanogels were localized in the central region of lymph node and that the uptake was largely by the macrophages. In vitro and in vivo toxicity results indicated that the dextran-based nanogels were of low cytotoxicity at a polymer concentration up to 1,000 μg/mL and harmless to normal liver and kidney organs in mice at an intravenous dose of 1.25 mg/kg. The results of this study suggest that NIR-emitting polymeric nanogels based on bioreducible dextran-deoxycholic acid conjugates show high potential as fluorescence nanoprobes for safe and noninvasive SLN mapping.

  9. EFFECT OF DEXTRAN-graft-POLYACRYLAMIDE INTERNAL STRUCTURE ON FLOCCULATION PROCESS PARAMETERS

    SciTech Connect

    Bezugla, T.; Kutsevol, N.; Shyichuk, A.; Ziolkowska, D.

    2008-08-28

    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. 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.

  11. Acid-Degradable Cationic Dextran Particles for the Delivery of siRNA Therapeutics

    PubMed Central

    Cohen, Jessica L.; Schubert, Stephanie; Wich, Peter R.; Cui, Lina; Cohen, Joel A.; Mynar, Justin L.; Fréchet, Jean M. J.

    2011-01-01

    We report a new acid-sensitive, biocompatible and biodegradable microparticulate delivery system, spermine modified acetalated-dextran (Spermine-Ac-DEX), which can be used to efficiently encapsulate siRNA. These particles demonstrated efficient gene knockdown in HeLa-luc cells with minimal toxicity. This knockdown was comparable to that obtained using Lipofectamine, a commercially available transfection reagent generally limited to in vitro use due to its high toxicity. PMID:21539393

  12. Inclusion of high molecular weight dextran in calcium phosphate-mediated transfection significantly improves gene transfer efficiency.

    PubMed

    Wu, C; Lu, Y

    2007-05-15

    Calcium phosphate-based mammalian cell transfection is a widely used gene transfer technology. To facilitate the efficiency of this gene transfer method, several polysaccharide compounds were tested and evaluated for their effectiveness in enhancing DNA transfection. Using a HIV-1-derived lentivirus vector plasmid as a gene transfer indicator, we demonstrated that the addition of high molecular weight dextran-500 at 0.6-1.2% in the 2x Hepes buffered saline (HBS) increased transfection efficiency by over 50% (as reflected by the number of GFP-positive cells) and increased the titer of resulting lentivirus vector particles even more (up to 4-fold). This enhancement of transfection efficiency was further increased when higher molecular weight dextran formulations were used in place of dextran-500, and also when dextran was used in combination with polybrene, another polycationic chemical compound. Examination of transfected cells showed that dextran had no apparent adverse effect on cell viability and growth. Our data represent the first report showing that dextran can be used to enhance calcium phosphate-mediated gene transfer; this may be useful in applications for the generation of high-titer virus vector stocks using transient transfection technology.

  13. Docusate Sodium and Pregnancy

    MedlinePlus

    ... live chat Live Help Fact Sheets Share Docusate Sodium Friday, 01 April 2016 In every pregnancy, a ... This sheet talks about whether exposure to docusate sodium may increase the risk for birth defects over ...

  14. Diclofenac sodium overdose

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/002630.htm Diclofenac sodium overdose To use the sharing features on this page, please enable JavaScript. Diclofenac sodium is a prescription medicine used to relieve pain ...

  15. Sodium Ferric Gluconate Injection

    MedlinePlus

    Sodium ferric gluconate injection is used to treat iron-deficiency anemia (a lower than normal number of ... are also receiving the medication epoetin (Epogen, Procrit). Sodium ferric gluconate injection is in a class of ...

  16. Fractional excretion of sodium

    MedlinePlus

    FE sodium; FENa ... to a lab. There, they are examined for salt (sodium) and creatinine levels. Creatinine is a chemical waste ... your normal foods with a normal amount of salt, unless otherwise instructed by your health care provider. ...

  17. [Indirect articular lymphography using Tc 99m-labeled Dextran in animals].

    PubMed

    Albuquerque, M; Pedroso de Lima, J; Cardoso, A; Mendes, F; Pires, J; Canha, N; Branco, R

    1990-01-01

    Looking for a standardization of the articular lymphoscintigraphy, an experimental research was conducted on 14 dogs injected in the ankle, with 2.5 mCi of 99m Tc-labeled dextran (P.M. = 70,000). Good scintigraphic images of the lymphatic system have been obtained. After having collected blood samples during the experimentation as well as aliquots of organs and of tissues, after the necropsy of the animal, it was verified that the 99m Tc-labeled dextran was useful for quantitative studies of the articular lymphatic drainage. The activities attained, in the drainage lymph nodes of injected articulation, are 152 times superior to those obtained in the kidney and one gramma of popliteal ganglion was 8929 times more active than one gramma of blood. The dextran 70,000, widely used in our clinical routine, can be injected to the human being, without any risk, and it may be the tracer which permits studies of the articular lymphatic drainage and the usage of the lymphoscintigraphy, already in expansion in many other Medicine branches, in the articular studies, nowadays.

  18. 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. PMID:27451271

  19. 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.

  20. Regulation of dendrimer/dextran material performance by altered tissue microenvironment in inflammation and neoplasia.

    PubMed

    Oliva, Nuria; Carcole, Maria; Beckerman, Margarita; Seliktar, Sivan; Hayward, Alison; Stanley, James; Parry, Nicola Maria Anne; Edelman, Elazer R; Artzi, Natalie

    2015-01-28

    A "one material fits all" mindset ignores profound differences in target tissues that affect their responses and reactivity. Yet little attention has been paid to the role of diseased tissue on material performance, biocompatibility, and healing capacity. We assessed material-tissue interactions with a prototypical adhesive material based on dendrimer/dextran and colon as a model tissue platform. Adhesive materials have high sensitivity to changes in their environment and can be exploited to probe and quantify the influence of even subtle modifications in tissue architecture and biology. We studied inflammatory colitis and colon cancer and found not only a difference in adhesion related to surface chemical interactions but also the existence of a complex interplay that determined the overall dendrimer/dextran biomaterial compatibility. Compatibility was contextual, not simply a constitutive property of the material, and was related to the extent and nature of immune cells in the diseased environment present before material implantation. We then showed how to use information about local alterations of the tissue microenvironment to assess disease severity. This in turn guided us to an optimal dendrimer/dextran formulation choice using a predictive model based on clinically relevant conditions. PMID:25632035

  1. Preparation and characterization of SDF-1α-chitosan-dextran sulfate nanoparticles.

    PubMed

    Bader, Andrew R; Li, Tina; Wang, Weiping; Kohane, Daniel S; Loscalzo, Joseph; Zhang, Ying-Yi

    2015-01-01

    Chitosan (CS) and dextran sulfate (DS) are charged polysaccharides (glycans), which form polyelectrolyte complex-based nanoparticles when mixed under appropriate conditions. The glycan nanoparticles are useful carriers for protein factors, which facilitate the in vivo delivery of the proteins and sustain their retention in the targeted tissue. The glycan polyelectrolyte complexes are also ideal for protein delivery, as the incorporation is carried out in aqueous solution, which reduces the likelihood of inactivation of the proteins. Proteins with a heparin-binding site adhere to dextran sulfate readily, and are, in turn, stabilized by the binding. These particles are also less inflammatory and toxic when delivered in vivo. In the protocol described below, SDF-1α (Stromal cell-derived factor-1α), a stem cell homing factor, is first mixed and incubated with dextran sulfate. Chitosan is added to the mixture to form polyelectrolyte complexes, followed by zinc sulfate to stabilize the complexes with zinc bridges. The resultant SDF-1α-DS-CS particles are measured for size (diameter) and surface charge (zeta potential). The amount of the incorporated SDF-1α is determined, followed by measurements of its in vitro release rate and its chemotactic activity in a particle-bound form. PMID:25650558

  2. Dextran-coated superparamagnetic amorphous Fe–Co nanoalloy for magnetic resonance imaging applications

    SciTech Connect

    An, Lu; Yu, Yanrong; Li, Xuejian; Liu, Wei; Yang, Hong; Wu, Dongmei; Yang, Shiping

    2014-01-01

    Graphical abstract: A dextran-coated Fe–Co nanoalloy was developed serving as a sensitive contrast agent for magnetic resonance imaging applications. - Highlights: • Amorphous Fe–Co nanoalloy was prepared via wet chemical reduction approach. • The Fe–Co nanoalloy is water-soluble, stable, and biocompatible. • The Fe–Co nanoalloy is superparamagnetic. • The Fe–Co nanoalloy exhibits T{sub 2}-weighted MR enhancement both in vitro and in vivo. - Abstract: For magnetic resonance imaging applications, a facile approach for water-soluble dextran coated amorphous Fe–Co nanoalloy was developed. The as-synthesized nanoalloy had a diameter of 9 nm with a narrow size distribution and showed superparamagnetic property with a saturated magnetization (Ms) of 25 emu/g. In vitro cytotoxicity test revealed that it was biocompatible at a concentration below 120 μg/mL. It can be uptaken by HeLa cells effectively and resulted in the obvious T{sub 2} effect after internalization. Biodistribution studies in conjunction with inductively coupled plasma-atomic emission spectroscopy (ICP-AES) confirmed that Fe–Co nanoalloy was preferentially accumulated in lung and spleen after intravenous injection for 4 h. In vivo MRI, dextran-coated Fe–Co nanoalloy can serve as a sensitive contrast agent for MR imaging, especially in the spleen, so we believe that it maybe hold great promise for diagnosis of splenic disease by appropriately functionalizing their surface.

  3. 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. PMID:26922047

  4. 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.

  5. Magnetic field dependence of the diffusion of single dextran molecules within a hydrogel containing magnetite nanoparticles.

    PubMed

    Al-Baradi, Ateyyah M; Mykhaylyk, Oleksandr O; Blythe, Harry J; Geoghegan, Mark

    2011-03-01

    We consider the effect of applied magnetic fields on the diffusion of single dextran molecules labeled with fluorescein isothiocyanate within a ferrogel [a composite of magnetite nanoparticles in a poly(methacrylic acid) hydrogel] using fluorescence correlation spectroscopy. We show that the mesh size of the ferrogel is controlled by the applied magnetic field, B, and scales as exp(-(4)√ξ(3)B(2)/2μ(0)k(B)T), where ξ is a correlation length, μ(0) the magnetic constant, k(B) the Boltzmann constant, and T is the absolute temperature. The diffusion coefficient of the dextran can be modeled with a simple Stokes-Einstein law, containing the same scaling behavior with magnetic field as the swelling of the hydrogel. Furthermore, the magnetic field-dependent release of dextran from the hydrogel is also controlled by the same relationship. The samples were characterized by small angle x-ray scattering (SAXS) and magnetometry experiments. Magnetic hysteresis loops from these ferrogels and zero field cooled∕field cooled measurements reveal single domain ferromagnetic behavior at room temperature with a similar coercivity for both as-prepared and fully swollen ferrogels, and for increasing magnetic nanoparticle concentration. SAXS experiments, such as the hysteresis loops, show that magnetite does not aggregate in these gels.

  6. 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

    2015-12-01

    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.

  7. The potentiation of human C1-inhibitor by dextran sulphate is transient in vivo: studies in a rat model.

    PubMed

    Bos, I G; van Mierlo, G J; Bleeker, W K; Rigter, G M; te Velthuis, H; Dickneite, G; Hack, C E

    2001-08-01

    C1-inhibitor (C1-Inh) is an important regulator of inflammatory reactions because it is a potent inhibitor of the contact and complement system. C1-Inh application in inflammatory disease is, however, restricted because of the high doses required. The glycosaminoglycan-like molecule dextran sulphate (DXS) enhances C1-Inh function in vitro. Hence, we investigated whether co-administration with dextran sulphate reduces the amount of C1-Inh required, through enhancement in vivo. C1-Inh potentiation was measured in a newly developed C1s-inactivation assay that is based on activation of C4 by purified C1s. Activated C4 in rat plasma was quantified with a newly developed ELISA. Human C1-Inh (2.5 microM) inhibited C1s in rat plasma 55-fold faster in the presence of dextran sulphate (15 kDa, 5 microM). To study the stability of the complex in vivo, rats were given a mixture of C1-Inh (10 mg/kg) and dextran sulphate (3 mg/kg). C1-Inh activity during 5 h was analyzed ex vivo with the C1s inactivation assay. The noncovalent C1-Inh-dextran sulphate complex resulted in a transient enhancement of the inhibitory capacity of C1-Inh, lasting for 60-90 min. Dextran sulphate did not affect plasma clearance of C1-Inh. We conclude that the enhanced inhibitory capacity of C1-Inh complexed to dextran sulphate is transient in vivo. Hence, co-administration of these compounds seems a feasible approach to achieve short-term inhibition of complement in vivo.

  8. 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. PMID:25576813

  9. 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.

  10. 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. PMID:22525936

  11. Modelling Cometary Sodium Tails

    NASA Astrophysics Data System (ADS)

    Birkett, K. S.; Jones, G. H.; Coates, A. J.

    2013-12-01

    Neutral sodium is readily observed in cometary spectra and can be seen to form its own distinct tail at high activity comets. Solar radiation pressure accelerates the sodium atoms antisunward and, as strong sodium absorption lines are present in the solar spectrum, the magnitude of this force is dependent upon the Doppler shift of the incident solar radiation. Therefore the heliocentric velocity of the sodium atom directly determines its acceleration. This can produce unique effects, such as a stagnation region. Sodium is relatively easy to detect and so can potentially be used to trace mechanisms in the coma that are otherwise difficult to observe. The source of neutral sodium in the tail currently remains unknown. We have therefore developed a new, three dimensional Monte-Carlo model of neutral cometary sodium in order to facilitate testing of different source production functions. It includes weightings due to neutral sodium lifetime, variation of cometary sodium emission due to Fraunhofer absorption lines and solar flux variation with heliocentric distance. The Swings and Greenstein effects, which can have particularly dramatic effects in near-Sun comets, are also considered comprehensively. Preliminary results from this model are presented, focusing on a comparison of predictions of the neutral sodium tail of Comet C/2012 S1 (ISON) with initial observations.

  12. Lactobacillus casei secreting alpha-MSH induces the therapeutic effect on DSS-induced acute colitis in Balb/c Mice.

    PubMed

    Yoon, Sun-Woo; Lee, Chul-Ho; Kim, Jeong-Yoon; Kim, Jie-Youn; Sung, Moon-Hee; Poo, Haryoung

    2008-12-01

    The neuropeptide alpha-melanocyte-stimulating hormone (alpha- MSH) has anti-inflammatory property by downregulating the expressions of proinflammatory cytokines. Because alpha-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes alpha-MSH (L. casei-alpha-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the alpha-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and alpha-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-alpha-MSH on the colitis, L. casei or L. casei-alpha-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-alpha-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: 14.45+/-0. 2 g; L. casei-alpha- MSH: 18.2+/-0.12 g), colitis score (DSS alone: 3.6+/-0.4; L. casei-alpha-MSH: 1.4+/-0.6), MPO activity (DSS alone: 42.7+/-4.5 U/g; L. casei-alpha-MSH: 10.25+/-0.5 U/g), survival rate, and histological damage compared with the DSS alone mice. L. casei-alpha-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and NF-kappaB activation. The alpha-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases.

  13. Acute Bronchitis

    MedlinePlus

    ... tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when ...

  14. Enhancement of irradiation effects on cancer cells by cross-linked dextran-coated iron oxide (CLIO) nanoparticles

    NASA Astrophysics Data System (ADS)

    Huang, Fu-Kuo; Chen, Wen-Chang; Lai, Sheng-Feng; Liu, Chi-Jen; Wang, Cheng-Liang; Wang, Chang-Hai; Chen, Hsiang-Hsin; Hua, Tzu-En; Cheng, Yi-Yun; Wu, M. K.; Hwu, Y.; Yang, Chung-Shi; Margaritondo, G.

    2010-01-01

    We investigated iron oxide nanoparticles with two different surface modifications, dextran coating and cross-linked dextran coating, showing that their different internalization affects their capability to enhance radiation damage to cancer cells. The internalization was monitored with an ultrahigh resolution transmission x-ray microscope (TXM), indicating that the differences in the particle surface charge play an essential role and dominate the particle-cell interaction. We found that dextran-coated iron oxide nanoparticles cannot be internalized by HeLa and EMT-6 cells without being functionalized with amino groups (the cross-linked dextran coating) that modify the surface potential from -18 mV to 13.4 mV. The amount of cross-linked dextran-coated iron oxide nanoparticles uptaken by cancer cells reached its maximum, 1.33 × 109 per HeLa cell, when the co-culture concentration was 40 µg Fe mL-1 or more. Standard tests indicated that these internalized nanoparticles increased the damaging effects of x-ray irradiation, whereas they are by themselves biocompatible. These results could lead to interesting therapy applications; furthermore, iron oxide also produces high contrast for magnetic resonance imaging (MRI) in the diagnosis and therapy stages.

  15. Enhancement of irradiation effects on cancer cells by cross-linked dextran-coated iron oxide (CLIO) nanoparticles.

    PubMed

    Huang, Fu-Kuo; Chen, Wen-Chang; Lai, Sheng-Feng; Liu, Chi-Jen; Wang, Cheng-Liang; Wang, Chang-Hai; Chen, Hsiang-Hsin; Hua, Tzu-En; Cheng, Yi-Yun; Wu, M K; Hwu, Y; Yang, Chung-Shi; Margaritondo, G

    2010-01-21

    We investigated iron oxide nanoparticles with two different surface modifications, dextran coating and cross-linked dextran coating, showing that their different internalization affects their capability to enhance radiation damage to cancer cells. The internalization was monitored with an ultrahigh resolution transmission x-ray microscope (TXM), indicating that the differences in the particle surface charge play an essential role and dominate the particle-cell interaction. We found that dextran-coated iron oxide nanoparticles cannot be internalized by HeLa and EMT-6 cells without being functionalized with amino groups (the cross-linked dextran coating) that modify the surface potential from -18 mV to 13.4 mV. The amount of cross-linked dextran-coated iron oxide nanoparticles uptaken by cancer cells reached its maximum, 1.33 x 10(9) per HeLa cell, when the co-culture concentration was 40 microg Fe mL(-1) or more. Standard tests indicated that these internalized nanoparticles increased the damaging effects of x-ray irradiation, whereas they are by themselves biocompatible. These results could lead to interesting therapy applications; furthermore, iron oxide also produces high contrast for magnetic resonance imaging (MRI) in the diagnosis and therapy stages. PMID:20023329

  16. Evaluation in vitro and in vivo of two labelling techniques of different 99mTc-dextrans for lymphoscintigraphy.

    PubMed

    Wingårdh, K; Strand, S E

    1989-01-01

    Five dextrans with different molecular weights and charges were labelled with 99mTc. The labelling methods presented by Henze et al. (1982a) and Ercan et al. (1985) were compared. The labelling efficiency was tested with gel column chromatography scanning (GCS), gel chromatography (GC) combined with the Anthrone test, paper chromatography (PC) and thin layer chromatography (TLC). The GCS technique always indicated a lower labelling efficiency than the PC and TLC techniques, which was due to a more optimal separation of the radioactive components. Gel chromatography in combination with the Anthrone test made it easy to identify the different radiochemical components in contrast to the other methods. Dextran solutions were injected subcutaneously bilaterally at the xiphoid processes in rabbits. The injection sites were massaged for 30 s. Uptake in the parasternal lymph nodes was registrated with a scintillation camera. The animals were killed and dissected at the end of the study. This investigation shows that the labelling method of Ercan et al. gives the highest labelling efficiency. Furthermore, the final pH (4.5) for the dextran solution makes it more useful for injection. For quality control of 99mTc-labelled dextran we recommend the Anthrone test as a complement to GC because it is a quick and simple method of determining the dextran content.

  17. 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

    2015-03-01

    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.

  18. Reaction of germinal centers in the T-cell-independent response to the bacterial polysaccharide alpha(1-->6)dextran.

    PubMed Central

    Wang, D; Wells, S M; Stall, A M; Kabat, E A

    1994-01-01

    Primary immunization of BALB/c mice with alpha(1-->6)dextran (DEX), a native bacterial polysaccharide, induces an unexpected pattern of splenic B-cell responses. After a peak of antibody-secreting B-cell response at day 4, deposition of dextran-anti-dextran immune complexes, as revealed by staining with both dextran and antibodies to dextran, occurs and persists in splenic follicles until at least the fourth week after immunization. Antigen-specific B cells appear and proliferate in such follicles, leading by day 11 to development of DEX-specific germinal centers as characterized by the presence of distinct regions of DEX+ peanut agglutinin-positive (PNA+) cells. At this time, fluorescence-activated cell sorter analysis also reveals the appearance of a distinct population of DEX+ PNA+ splenic B cells. In contrast, DEX+ PNA- cells, characterized by intense cytoplasmic staining, are present outside of splenic follicles, peak at day 4 to day 5, and persist until at least day 28. The frequency of these cells correlates with DEX-specific antibody-secreting cells, as detected by the ELISA-spot assay. Thus, in addition to the expected plasma cellular response, the typical T-cell-independent type II antigen, DEX, surprisingly also elicits the formation of antigen-specific germinal centers. These observations raise fundamental questions about the roles of germinal centers in T-cell-independent immune responses. Images PMID:7511812

  19. Sodium remote from Io

    NASA Astrophysics Data System (ADS)

    Brown, R. A.; Schneider, N. M.

    1981-12-01

    Measurements of sodium emission lines originating in the middle Jupiter magnetosphere are measured, confirming the wide dispersal of neutral sodium in the Jovian system in at least two distinct manifestations. Candidate neutral transport processes in the context of the observed kinematical signatures are discussed. It is argued that the normal emission feature is produced by sodium atoms on bound elliptical orbits originating in the Io sodium cloud but with apojove in the field of view. Observations of the fast sodium feature indicate that atoms episodically acquire a broad range of line-of-sight velocities above the Jupiter gravitational escape speed and far above the speeds characteristic of surface-sputtered atoms. Three suggested reactions are distinguished according to (1) production rates based on estimated plasmaspheric properties, (2) kinematical signature, and (3) the timing of occurrences of the fast sodium feature.

  20. Synthesis and characterization of acetalated dextran polymer and microparticles with ethanol as a degradation product.

    PubMed

    Kauffman, Kevin J; Do, Clement; Sharma, Sadhana; Gallovic, Matthew D; Bachelder, Eric M; Ainslie, Kristy M

    2012-08-01

    In the field of drug delivery, pH-sensitive polymeric microparticles can be used to release therapeutic payloads slowly in extracellular conditions (pH 7.4) and faster in more acidic areas in vivo, such as sites of inflammation, tumors, or intracellular conditions. Our group currently uses and is further developing the pH-sensitive polymer acetalated dextran (Ac-DEX), which is a biodegradable polymer with highly tunable degradation kinetics. Ac-DEX has displayed enhanced delivery of vaccine and drug components to immune and other cells, making it an extremely desirable polymer for immune applications. Currently, one of the degradation products of Ac-DEX is methanol, which may cause toxicity issues if applied at high concentrations with repeated doses. Therefore, in this manuscript we report the first synthesis and characterization of an Ac-DEX analog which, instead of a methanol degradation product, has a much safer ethanol degradation product. We abbreviate this ethoxy acetal derivatized acetalated dextran polymer as Ace-DEX, with the 'e' to indicate an ethanol degradation product. Like Ac-DEX, Ace-DEX microparticles have tunable degradation rates at pH 5 (intracellular). These rates range from hours to several days and are controlled simply by reaction time. Ace-DEX microparticles also show minimal cytotoxicity compared to commonly used poly(lactic-co-glycolic acid) (PLGA) microparticles when incubated with macrophages. This study aims to enhance the biocompatibility of acetalated dextran-type polymers to allow their use in high volume clinical applications such as multiple dosing and tissue engineering.

  1. /sup 99m/Tc dextran: a new blood-pool-labeling agent for radionuclide angiocardiography

    SciTech Connect

    Henze, E.; Robinson, G.D.; Kuhl, D.E.; Schelbert, H.R.

    1982-04-01

    We have explored the possibility of imaging the cardiac blood pool with dextran (Dx) labeled with /sup 99m/Tc (Tc) after Sn2+ reduction. Stannous dextran (SnDx) kits were prepared in advance and labeling was performed by adding /sup 99m/Tc. The labeling efficiency was greater than 95%. /sup 99m/Tc dextran (TcDx) was highly stable both in vivo and in vitro. In seven dogs we compared the quality of blood-pool images obtained with TcDx of different molecular weights (4 X 10(4) . Dx-40; 5 X 10(5) . Dx-500; 2 X 10(6) . Dx-2000) and with /sup 99m/Tc red blood cells (TcRBC) labeled in vitro, and determined the organ distribution of this new agent by whole-body scanning and blood sampling. TcDx provided high-quality cardiac blood-pool images up to 60 min after injection. The heart-to-lung ratios averaged 3.7 for TcDx-40, 3.9 for TcDx-500, and 5.4 for TcRBC at 60 min. Whereas TcDx-40 showed a relatively rapid initial urinary excretion and TcDx-2000 was degraded rapidly, TcDx-500 demonstrated the best kinetics for blood-pool imaging. Thus, TcDx is a new radiopharmaceutical with high labeling efficiency and stability. It overcomes a number of the limitations of currently used blood-labeling agents and may become useful for blood-pool imaging in man.

  2. Tc-99m dextran: a new blood-pool-labeling agent for radionuclide angiocardiography

    SciTech Connect

    Henze, E.; Robinson, G.D.; Kuhl, D.E.; Schelbert, H.R.

    1982-04-01

    We have explored the possibility of imaging the cadiac blood pool with dextran (Dx) labeled with Tc-99m (Tc) after Sn/sup 2 +/ reduction. Stannous dextrane (SnDx) kits were prepared in advance and labeling was performed by adding Tc-99m. The labeling efficiency was greater than 95%. Technetium-99m dextran (TcDx) was highly stable both in vivo and in vitro. In seven dogs we compared the quality of blood-pool images obtained with TcDx of different molecular weights ( 4 x 10/sup 4/ = Dx-40; 5 x 10/sup 5/ = Dx-500; 1 x 10/sup 6/ = Dx-2000) and with Tc-99m red blood cells (TcRBC) labeled in vitro, and determined the organ distribution of this new agent by whole-body scanning and blood sampling. TcDx provided high-quality cardiac blood-pool images up to 60 min after injection. The heart-to-lung ratios averaged 3.7 for TcDx-40, 3.9 for TcDx-500, and 5.4 for TcRBC at 60 min. Whereas TcDx-40 showed a relatively rapid initial urinary excretion and TcDx-2000 was degraded rapidly, TcDx-500 demonstrated the best kinetics for blood-pool imaging. Thus, TcDx is a new radiopharmaceutical with high labeling efficiency and stability. It overcomes a number of the limitations of currently used blood-labeling agents and may become useful for blood-pool imaging in man.

  3. Bimolecular integrin–ligand interactions quantified using peptide-functionalized dextran-coated microparticles

    PubMed Central

    Sun, Jessie E. P.; Vranic, Justin; Composto, Russell J.; Streu, Craig; Billings, Paul C.; Bennett, Joel S.; Weisel, John W.

    2012-01-01

    Integrins play a key role in cell–cell and cell–matrix interactions. Artificial surfaces grafted with integrin ligands, mimicking natural interfaces, have been used to study integrin-mediated cell adhesion. Here we report the use of a new chemical engineering technology in combination with single-molecule nanomechanical measurements to quantify peptide binding to integrins. We prepared latex beads with covalently-attached dextran. The beads were then functionalized with the bioactive peptides, cyclic RGDFK (cRGD) and the fibrinogen γC-dodecapeptide (H12), corresponding to the active sites for fibrinogen binding to the platelet integrin αIIbβ3. Using optical tweezers-based force spectroscopy to measure non-specific protein–protein interactions, we found the dextran-coated beads nonreactive towards fibrinogen, thus providing an inert platform for biospecific modifications. Using periodate oxidation followed by reductive amination, we functionalized the bead-attached dextran with either cRGD or H12 and used the peptide-grafted beads to measure single-molecule interactions with the purified αIIbβ3. Bimolecular force spectroscopy revealed that the peptide-functionalized beads were highly and specifically reactive with the immobilized αIIbβ3. Further, the cRGD- and H12-functionalized beads displayed a remarkable interaction profile with a bimodal force distribution up to 90 pN. The cRGD–αIIbβ3 interactions had greater binding strength than that of H12–αIIbβ3, indicating that they are more stable and resistant mechanically, consistent with the platelet reactivity of RGD-containing ligands. Thus, the results reported here describe the mechanistic characteristics of αIIbβ3–ligand interactions, confirming the utility of peptide-functionalized latex beads for the quantitative analysis of molecular recognition. PMID:22120019

  4. Transglutaminase-catalyzed site-specific glycosidation of catalase with aminated dextran.

    PubMed

    Valdivia, Aymara; Villalonga, Reynaldo; Di Pierro, Prospero; Pérez, Yunel; Mariniello, Loredana; Gómez, Leissy; Porta, Raffaele

    2006-04-10

    An enzymatic approach, based on a transglutaminase-catalyzed coupling reaction, was investigated to modify bovine liver catalase with an end-group aminated dextran derivative. We demonstrated that catalase activity increased after enzymatic glycosidation and that the conjugate was 3.8-fold more stable to thermal inactivation at 55 degrees C and 2-fold more resistant to proteolytic degradation by trypsin. Moreover, the transglutaminase-mediated modification also improved the pharmacokinetics behavior of catalase, increasing 2.5-fold its plasma half-life time and reducing 3-fold the total clearance after its i.v. administration in rats. PMID:16446004

  5. Effects of metabolic acidosis and alkalosis on sodium and calcium transport in the dog kidney.

    PubMed

    Sutton, R A; Wong, N L; Dirks, J H

    1979-05-01

    Clearance and micropuncture studies have been performed in dogs to examine the effects of acute and chronic metabolic acidosis and acute alkalosis on tubular sodium and calcium transport. Acute metabolic acidosis, induced by the infusion of hydrochloric acid, decreased proximal fluid reabsorption and increased the fractional delivery of sodium and calcium to the distal tubule, but not to the final urine. In comparison with normal dogs, dogs with chronic metabolic acidosis (induced by feeding ammonium chloride) showed an increase in proximal fluid reabsorption and a dissociation of calcium from sodium reabsorption more distally, leading to an increased delivery of calcium relative to sodium at the distal tubule and in the final urine. The infusion of sodium bicarbonate to correct chronic metabolic acidosis, both in intact and thyroparathyroidectomized (TPTX) dogs, reduced proximal fluid reabsorption and caused a selective enhancement of calcium reabsorption relative to sodium in the more distal nephron, resulting in a reversal of the dissociation observed in acidosis, both at the distal tubule and in the final urine. By contrastin fusion of sodium chloride in parathyroid-intact acidotic dogs did not reduce proximal fluid reabsorption or enhance tubular calcium reabsorption. In nonacidotic dogs, both intact and TPTX, infusion of sodium bicarconate to induce acute alkalosis resulted in selhese data demonstrate the presence of a component of tubular calcium reabsorption situated beyond the proximal tubule, which is inhibited by chronic (but not acute) metabolic acidosis and enhanced by metabolic alkalosis (or bicarbonate infusion) independently of parathyroid hormone. PMID:480784

  6. Toxicity of aerosols of sodium reaction products.

    PubMed

    Zwicker, G M; Allen, M D; Stevens, D L

    1979-01-01

    Sodium is used as the heat transfer medium in several new energy technologies such as liquid-metal fast-breeder reactors and solar-thermal collection systems. Because sodium burns in air and reacts violently with water, the potential exists for an airborne release of sodium combustion products and subsequent human exposure. To help evaluate the potential short-term hazard from an accidental sodium fire, male juvenile or adult Wistar rats were exposed to sodium aerosols for 2 hours to determine the dose at which 50 percent of the animals were affected (ED50) for each age group. The estimated ED50 of 510 microgram/l for adults was not significantly different from the estimated ED50 of 489 microgram/l for juveniles. The incidence of acute laryngitis, attributed to exposure, was three times higher for juvenile rats than for adults, and the degree of severity of this lesion was significantly (P less than 0.05) higher for juveniles.

  7. Impact of supramolecular interactions of dextran-β-cyclodextrin polymers on invertase activity in freeze-dried systems.

    PubMed

    Santagapita, Patricio R; Mazzobre, M Florencia; Buera, M Pilar; Ramirez, Héctor L; Brizuela, Leissy Gómez; Corti, Horacio R; Villalonga, Reynaldo

    2015-01-01

    β-Cyclodextrin (β-CD)-grafted dextrans with spacer arms of different length were employed to evaluate the impact of supramolecular interactions on invertase activity. The modified dextrans were used as single additives or combined with trehalose in freeze-dried formulations containing invertase. Enzyme activity conservation was analyzed after freeze-drying and thermal treatment. The change of glass transition temperature (Tg ) was also evaluated and related to effective interactions. Outstanding differences on enzyme stability were mainly related to the effect of the spacer arm length on polymer-enzyme interactions, since both the degree of substitution and the molecular weight were similar for the two polymers. This change of effective interactions was also manifested in the pronounced reduction of Tg values, and were related to the chemical modification of the backbone during oxidation, and to the attachment of the β-CD units with spacer arms of different length on dextran.

  8. Separation of microsomal cytochrome b5 via phase separation in a mixed solution of Triton X-114 and charged dextran.

    PubMed

    Tani, H; Ooura, T; Kamidate, T; Kamataki, T; Watanabe, H

    1998-04-24

    The successful introduction of a charged dextran into the Triton X-114 phase separation system for the selective extraction of cytochrome b5 (cyt. b5) in liver microsomes is described. In the absence of charged dextran, 55% of total microsomal proteins and 84% of cyt. b5 were extracted into the surfactant-rich phase. In the presence of anionic dextran sulfate, the extractability of total microsomal proteins was greatly reduced while that of cyt. b5 was increased. After triplicate extraction, cyt. b5 was purified more than 10-fold from microsomes with a recovery of 91% in the surfactant-rich phase. In view of its operational simplicity, this method provides a good means for the partial purification of cyt. b5 prior to chromatographic separations.

  9. 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. PMID:25958243

  10. Impregnation of cotton fabric with silver nanoparticles synthesized by dextran isolated from bacterial species Leuconostoc mesenteroides T3.

    PubMed

    Davidović, Slađana; Miljković, Miona; Lazić, Vesna; Jović, Danica; Jokić, Bojan; Dimitrijević, Suzana; Radetić, Maja

    2015-10-20

    This study was aimed to highlight the possibility of cotton fabric impregnation with silver nanoparticles synthesized by dextran isolated from Leuconostoc mesenteroides T3 in order to obtain antimicrobial properties. The fabrication of dextran was proved by FTIR spectroscopy. Particle sizes of synthesized dextran and silver nanoparticles were measured by dynamic light scattering method. The presence of silver nanoparticles on the surface of cotton fabric was confirmed by scanning electron microscopy, X-ray diffraction measurements and reflectance spectrophotometry. Antimicrobial activity of cotton fabric impregnated with silver nanoparticles was tested against bacteria Escherichia coli and Staphylococcus aureus, and fungus Candida albicans. The results indicated that synthesized silver nanoparticles can provide satisfactory antimicrobial activity. However, maximum reduction (99.9%) of all tested microorganisms can be obtained only when 1.0mmolL(-1) colloid consisting of silver nanoparticles is applied. PMID:26256192

  11. Impact of supramolecular interactions of dextran-β-cyclodextrin polymers on invertase activity in freeze-dried systems.

    PubMed

    Santagapita, Patricio R; Mazzobre, M Florencia; Buera, M Pilar; Ramirez, Héctor L; Brizuela, Leissy Gómez; Corti, Horacio R; Villalonga, Reynaldo

    2015-01-01

    β-Cyclodextrin (β-CD)-grafted dextrans with spacer arms of different length were employed to evaluate the impact of supramolecular interactions on invertase activity. The modified dextrans were used as single additives or combined with trehalose in freeze-dried formulations containing invertase. Enzyme activity conservation was analyzed after freeze-drying and thermal treatment. The change of glass transition temperature (Tg ) was also evaluated and related to effective interactions. Outstanding differences on enzyme stability were mainly related to the effect of the spacer arm length on polymer-enzyme interactions, since both the degree of substitution and the molecular weight were similar for the two polymers. This change of effective interactions was also manifested in the pronounced reduction of Tg values, and were related to the chemical modification of the backbone during oxidation, and to the attachment of the β-CD units with spacer arms of different length on dextran. PMID:25736897

  12. THE ROLE OF SODIUM CHANNELS IN CHRONIC PAIN

    PubMed Central

    Levinson, Simon R.; Luo, Songjiang; Henry, Michael A.

    2012-01-01

    Here we review recent research into the mechanisms of chronic pain that has focused on neuronal sodium channels, a target of classic analgesic agents. We first discuss evidence that specific sodium channel isoforms are essential for the detection and conduction of normal acutely painful stimuli from nociceptors. We then review findings that show changes in sodium channel expression and localization in chronic inflammation and nerve injury in animal and human tissues. We conclude by discussing the role that myelination plays in organizing and maintaining sodium channel clusters at nodes of Ranvier in normal development and how inflammatory processes or nerve injury alter the characteristics of such clusters. Based on these findings, we suggest that chronic pain may in part result from partial demyelination of axons during chronic injury, which creates aberrant sodium channel clusters that serve as sites of ectopic sensitivity or spontaneous activity. PMID:22806363

  13. Clinical effects of nedocromil sodium on allergen-related mechanisms.

    PubMed

    Bleecker, E R; Mason, P L; Moore, W C

    1996-11-01

    Many studies have demonstrated the ability of nedocromil sodium to block the acute response to allergen in persons who are sensitive to allergen. One study with subjects sensitive to ragweed showed a significant protective effect after a single 4 mg dose of nedocromil sodium, with no further protection achieved at higher doses. Numerous studies have also shown the ability of the drug to reduce or abolish the late asthmatic response in sensitive subjects when it was given before allergen challenge. Nedocromil sodium has also been shown to prevent the subsequent development of bronchial hyperresponsiveness. In addition, nedocromil sodium prevented the late asthmatic response when given after allergen challenge and an intact early response. These findings suggest that nedocromil sodium may be preventing the inflammatory events initiated by mast cell mediator and cytokine release.

  14. Toxicological studies on cefuroxime sodium.

    PubMed

    Capel-Edwards, K; Atkinson, R M; Pratt, D A

    1979-05-01

    The intravenous LD50 of cefuroxime sodium for mice was 10.4 g/kg. The maximum dosage administered in other acute toxicity tests was well tolerated by mice (10 g/kg, subcutaneous), by rats (4 g/kg, intravenous, 5 g/kg, subcutaneous) and by cats, dogs and monkeys (2 g/kg, intramuscularly). Cefuroxime sodium was administered subcutaneously (s.c.) or intramuscularly (i.m.) for 3 months to rats (100, 300 or 900 mg/kg/day) followed by a recovery period, and also for 6 months to rats and dogs (50, 150 or 450 mg/kg/day) and for 1 month to monkeys (150 or 450 mg/kg/day). In all these tests there were no serious toxic effects. Minor haematological changes were attributable in part if not entirely to haemorrhage and tissue reaction at the site of injection of large doses. In rats large doses caused some increase in urine volume and electrolyte excretion, and slightly aggravated an age related nephropathy. Administration to rats intravenously (i.v.) for1 month of up to 400 mg/kg/day had no toxic effects. In reproduction studies on mice and rabbits there were no adverse effects on fertility, organogenesis or the rearing of young.

  15. Safety of total dose iron dextran infusion in geriatric patients with chronic kidney disease and iron deficiency anemia.

    PubMed

    Dossabhoy, Neville R; Turley, Steven; Gascoyne, Rebecca; Tapolyai, Mihaly; Sulaiman, Karina

    2014-08-01

    There are limited data on total dose infusion (TDI) using iron dextran in geriatric chronic kidney disease (CKD) patients with iron-deficiency anemia (IDA). Our goal was to evaluate the safety of TDI in this setting. We conducted a retrospective chart review spanning a 5 year period (2002-2007), including all patients with CKD and IDA who were treated with iron dextran TDI. Patient demographics were noted, and laboratory values for creatinine, hemoglobin and iron stores were recorded pre- and post-dose. TDI diluted in normal saline was administered intravenously over 4-6 hours after an initial test dose. One hundred fifty-three patients received a total of 250 doses of TDI (mean ± SD=971 ± 175 mg); age was 69 ± 12 years and creatinine 3.3 ± 1.9 mg/dL. All stages of CKD were represented (stage 4 commonest). Hemoglobin and iron stores improved post-TDI (P<0.001). None of the patients experienced an anaphylactic reaction or death. Adverse events (AEs) were noted in 8 out of 250 administered doses (3.2%). The most common AEs were itching, chills and back pain. One hundred and ten doses of high molecular weight (HMW) iron dextran produced 6 AEs (5.45%), whereas 140 doses of low molecular weight (LMW) iron dextran produced 2 AEs (1.43%), a non-significant trend (P=0.1433 by Fishers Exact Test). Iron dextran TDI is relatively safe and effective in correcting IDA in geriatric CKD patients. Fewer AEs were noted with the LMW compared to the HMW product. LMW iron dextran given as TDI can save both cost and time, helping to alleviate issues of non-compliance and patient scheduling.

  16. Biologic comparison of inhaled insulin formulations: Exubera™ and novel spray-dried engineered particles of dextran-10.

    PubMed

    Kuehl, Philip J; Cherrington, Alan; Dobry, Dan E; Edgerton, Dale; Friesen, Dwayne T; Hobbs, Charles; Leach, Chet L; Murri, Brice; Neal, Doss; Lyon, David K; Vodak, David T; Reed, Matthew D

    2014-12-01

    Inhaled peptides and proteins have promise for respiratory and systemic disease treatment. Engineered spray-dried powder formulations have been shown to stabilize peptides and proteins and optimize aerosol properties for pulmonary delivery. The current study was undertaken to investigate the in vitro and in vivo inhalation performance of a model spray-dried powder of insulin and dextran 10 in comparison to Exubera™. Dextrans are a class of glucans that are generally recognized as safe with optimum glass transition temperatures well suited for spray drying. A 70% insulin particle loading was prepared by formulating with 30% (w/v) dextran 10. Physical characterization revealed a "raisin like" particle. Both formulations were generated to produce a similar bimodal particle size distribution of less than 3.5 μm MMAD. Four female Beagle dogs were exposed to each powder in a crossover design. Similar presented and inhaled doses were achieved with each powder. Euglycemia was achieved in each dog prior and subsequent to dosing and blood samples were drawn out to 245 min post-exposure. Pharmacokinetic analyses of post-dose insulin levels were similar for both powders. Respective dextran 10-insulin and Exubera exposures were similar producing near identical area under the curve (AUC), 7,728 ± 1,516 and 6,237 ± 2,621; concentration maximums (C max), 126 and 121 (μU/mL), and concentration-time maximums, 20 and 14 min, respectively. These results suggest that dextran-10 and other dextrans may provide a novel path for formulating peptides and proteins for pulmonary delivery.

  17. Comparison of a carboxylated terthiophene surface with carboxymethylated dextran layer for surface plasmon resonance detection of progesterone.

    PubMed

    Wang, Yijing; Partridge, Ashton; Wu, Yinqiu

    2016-09-01

    Functionalization of a gold surface is usually accomplished by covalent binding via self-assembled monolayers (SAMs) on the gold surface, followed by attachment of flexible polymeric linker layers such as dextran hydrogels. However, these techniques require multiple steps and also have nonspecific interactions and steric problems. In this study, a self-assembled carboxylated terthiophene monolayer was formed onto a gold surface to create a sensitive and stable surface plasmon resonance (SPR) biosensing system. Compared with a commercial carboxymethyl dextran chip (CM5), the terthiophene SAM surface provided more than six times more antibody-binding signals and nearly three times the SPR assay sensitivity for progesterone (P4). PMID:27288558

  18. Comparison of a carboxylated terthiophene surface with carboxymethylated dextran layer for surface plasmon resonance detection of progesterone.

    PubMed

    Wang, Yijing; Partridge, Ashton; Wu, Yinqiu

    2016-09-01

    Functionalization of a gold surface is usually accomplished by covalent binding via self-assembled monolayers (SAMs) on the gold surface, followed by attachment of flexible polymeric linker layers such as dextran hydrogels. However, these techniques require multiple steps and also have nonspecific interactions and steric problems. In this study, a self-assembled carboxylated terthiophene monolayer was formed onto a gold surface to create a sensitive and stable surface plasmon resonance (SPR) biosensing system. Compared with a commercial carboxymethyl dextran chip (CM5), the terthiophene SAM surface provided more than six times more antibody-binding signals and nearly three times the SPR assay sensitivity for progesterone (P4).

  19. [Preparation of novel magnetic dextran affinity adsorbents and their application to purify urokinase].

    PubMed

    Dong, Y S; Liang, F; Yu, X Y; Guo, L A; Chang, J H

    2001-01-01

    The reverse phase suspension and embedment technique were adopted to prepare magnetic dextran microsphere (MDMS). The dispersion medium was mixture of some organic solvents. Span-80 was used as stabilizer. The aqueous dextran with magnetic fluid was suspended in dispersion medium with epichlorohydrin as cross-linking reagent. The mixture was stirred for 30 minutes at room temperature and then heated at 70 degrees C for 4 hours, MDMS was thus obtained. MDMS was activated by epichlorohydrin on which 6-aminohexanoic acid, glycine or ethylene diamine was bonded as spacers. Then it was coupled with p-aminobenzamide, L-arginine methyl ester or guanidohexanoic acid and five magnetic affinity adsorbents were prepared. The MDMS was polydisperse particles with the size of 50-300 meshes and the content of Fe3O4 was about 6.2 per cent in the MDMS. Influence of some parameters such as viscosity and density of organic phase, the volume ratio of organic and aqueous phase, the quantity of surfactant and stirring speed on preparing MDMS was studied. Magnetic affinity adsorbents were used to purify crude urokinase in a bath mode and the effect of coupling reagents and ligands on results of purification was discussed. The bioactivity recovery was 40.0 to 60.7 per cent, the purification-fold was between 14.9 and 32.8, and the adsorptive capacity varies from 89 mg to 121 mg per milliliter of adsorbent. PMID:12541840

  20. Rapid microwave-assisted synthesis of dextran-coated iron oxide nanoparticles for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Osborne, Elizabeth A.; Atkins, Tonya M.; Gilbert, Dustin A.; Kauzlarich, Susan M.; Liu, Kai; Louie, Angelique Y.

    2012-06-01

    Currently, magnetic iron oxide nanoparticles are the only nanosized magnetic resonance imaging (MRI) contrast agents approved for clinical use, yet commercial manufacturing of these agents has been limited or discontinued. Though there is still widespread demand for these particles both for clinical use and research, they are difficult to obtain commercially, and complicated syntheses make in-house preparation unfeasible for most biological research labs or clinics. To make commercial production viable and increase accessibility of these products, it is crucial to develop simple, rapid and reproducible preparations of biocompatible iron oxide nanoparticles. Here, we report a rapid, straightforward microwave-assisted synthesis of superparamagnetic dextran-coated iron oxide nanoparticles. The nanoparticles were produced in two hydrodynamic sizes with differing core morphologies by varying the synthetic method as either a two-step or single-step process. A striking benefit of these methods is the ability to obtain swift and consistent results without the necessity for air-, pH- or temperature-sensitive techniques; therefore, reaction times and complex manufacturing processes are greatly reduced as compared to conventional synthetic methods. This is a great benefit for cost-effective translation to commercial production. The nanoparticles are found to be superparamagnetic and exhibit properties consistent for use in MRI. In addition, the dextran coating imparts the water solubility and biocompatibility necessary for in vivo utilization.

  1. Do cyclodextrins bound to dextran microspheres act as sustained delivery systems of drugs?

    PubMed

    Constantin, Marieta; Bucatariu, Sanda; Harabagiu, Valeria; Ascenzi, Paolo; Fundueanu, Gheorghe

    2014-07-20

    The use of cyclodextrins (CDs) for controlled delivery of drugs is largely presented in the literature. However, the question of whether CDs themselves linked to a polymeric network are able to sustain the release of drugs still persists. Here, CD immobilization within dextran microspheres is reported, and CD-dextran complexes were packed in a glass column and then, the retention time of different drugs and drug model compounds was determined by liquid chromatography. The release profiles of drugs and of drug model compounds (indole, 3-nitrophenol, p-hydroxybenzoic acid, diclofenac), characterized by different values of the retention time (high, moderate or low), were investigated. The release rates were quite high even for drugs that exhibit very high retention time (high association equilibrium constant). Moreover, the volume of the release fluid strongly influences the rate of drug release. As a whole, "the sink conditions" must be continuously maintained, since at each drug concentration in the release medium, equilibrium occurs between the free and the CD-bound drug.

  2. Formation of bowl-shaped nanoparticles by self-assembly of cinnamic acid-modified dextran.

    PubMed

    Zhang, Cuige; Yang, Suhan; Zhu, Ye; Zhang, Rongli; Liu, Xiaoya

    2015-11-20

    The self-assembly of amphiphilic copolymers has attracted much attention because of their various morphologies and potential applications. Bowl-shaped nanoparticles could apply in many aspects due to their interior cavity, specific concave structure and high surface area. In this study, dextran (Dex) was hydrophobic modified by cinnamic acid (CINN) via esterification reaction between the hydroxyl group of Dex and the carboxyl group of CINN. The modification degree of CINN could be achieved by changing the feed ratios between Dex, CINN and the coupling agent. The cinnamic acid-modified dextran (Dex-CINN) composed of Dex as hydrophilic segment and CINN as hydrophobic segment could self-assemble into bowl-shaped nanoparticles with a single dimple on the surface. Furthermore, the size of the dimples could be controlled by changing the modification degree of CINN, concentration of Dex-CINN and the rate of water addition. The morphologies of bowl-shaped nanoparticles were characterized by transmission electron microscopy (TEM) and scanning electron microscope (SEM).

  3. Configuration of bovine serum albumin adsorbed on polymer particles with grafted dextran corona.

    PubMed

    Vauthier, Christine; Lindner, Peter; Cabane, Bernard

    2009-03-01

    The configuration of BSA macromolecules adsorbed on the surfaces of poly(alkylcyanoacrylate) nanoparticles has been determined using small angle neutron scattering (SANS). The nanoparticles were made by anionic emulsion polymerization (AEP) and self-assembly of dextran-poly(isobutylcyanoacrylate) (PICBA) copolymers. They have a hydrophobic PICBA core and a hydrophilic dextran corona. In vivo, they are recognized by the macrophages of the mononuclear phagocyte system. The amount of BSA bound to the particles, at adsorption equilibrium, has been determined through immunodiffusion, immunoelectrophoresis, and SANS. For particles with a radius of 25.3nm, the adsorption was found to saturate at 64 adsorbed BSA molecules per particle. The configuration of the adsorbed BSA molecules was determined from the SANS scattering curves, first at full contrast, and then at contrast match. Both experiments indicate that the BSA molecules are adsorbed on the PICBA core, in a flat configuration. This result may be important for understanding the in vivo opsonization mechanisms of nanoparticles and their resulting biodistribution.

  4. A Novel Preparation Method for Camptothecin (CPT) Loaded Folic Acid Conjugated Dextran Tumor-Targeted Nanoparticles

    PubMed Central

    Zu, Yuangang; Wang, Dan; Zhao, Xiuhua; Jiang, Ru; Zhang, Qi; Zhao, Dongmei; Li, Yong; Zu, Baishi; Sun, Zhiqiang

    2011-01-01

    In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted nanoparticles were produced with a supercritical antisolvent (SAS) technique by using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an antisolvent. A factorial design was used to reveal the effect of various process parameters on the mean particle size (MPS) and morphology of the particles formed. Under the optimum operation conditions, Fa-DEX-CPT nanoparticles with a MPS of 182.21 nm were obtained. Drug encapsulation efficiency and loading efficiency were 62.13% and 36.12%, respectively. It was found that the concentrations of the camptothecin (CPT) and dextran solution had a major influence upon morphology and shape of the final product. In addition, the samples were characterized by Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) with the purpose of developing a suitable targeted drug delivery system for cancer chemotherapy. PMID:21845075

  5. One-pot synthesis of dextran decorated reduced graphene oxide nanoparticles for targeted photo-chemotherapy.

    PubMed

    Hu, Yanfang; He, Liang; Ding, Jianxun; Sun, Diankui; Chen, Li; Chen, Xuesi

    2016-06-25

    Graphene-based nanocarriers show great potential in photo-chemotherapy, however, to prepare desired reduced graphene oxide (rGO) nanoparticles in a facile way is still a challenge. Herein, a novel strategy has been presented to prepare rGO nanoparticle using dextran (Dex) as a reducing agent. In this strategy, Dex was directly conjugated on rGO by hydrogen bond and then self-assemble to form rGO/Dex nanoparticles. After decorated by dextran, rGO-based nanoparticles not only show excellent biocompatibility but also can load anticancer drug for photo-chemotherapy. The data of fourier transform infrared (FT-IR) analysis, Raman spectrum analysis, thermos-gravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), the transmission electron microscope (TEM) image and dynamic light scattering (DLS) measurements powerfully proved that the stable rGO-based nanoparticles with desired nanosize have been successfully prepared. To verify the photo-chemotherapy, anticancer drug, doxorubicin (DOX), has been loaded on rGO/Dex nanoparticles (rGO/DOX/Dex). And RGD, a kind of oligopeptide which can improve the intracellular uptake by αvβ3 recognition, also has been introduced (rGO/DOX/RDex). Compared with single chemotherapy, rGO/DOX/Dex and rGO/DOX/RDex combining the local specific chemotherapy and external near-infrared (NIR) photo-thermal therapy show higher therapeutic efficacy, endowing the desired rGO-based nanoparticle with great potential for cancer treatments. PMID:27083812

  6. Green Synthesis of Silver Nanoparticles: Effect of Dextran Molecular Weight Used as Stabilizing-Reducing Agent.

    PubMed

    Carré-Rangel, Luceldi; Alonso-Nuñez, Gabriel; Espinoza-Gómez, Heriberto; Flores-López, Lucía Z

    2015-12-01

    This paper describes an easy green chemistry method for the synthesis of silver nanoparticles (AgNPs). The AgNPs were obtained through the use of an aqueous silver nitrate solution (AgNO3), with dextrans aqueous solutions of different molecular weights acting as stabilizing and reducing agent, employing the chemical reduction method. We made a comparative study to determine which molecular weight dextran was the best stabilizing and reducing agent, and it was found that the molecular size of the stabilizing agent is inversely proportional to the size of the nanoparticle synthesized. The formation of the AgNPs was demonstrated by UV-Vis spectroscopy, atomic force microscopy (AFM), scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and transmission electron microscopy (TEM). SEM-EDS analysis shows the formation of particles with dendritic structure. TEM shows nanoparticles which are spherical in shape and 1-10 nm in size; also, the clear lattice fringes show highly crystalline AgNPs (FCC). PMID:26682423

  7. Magnetic Composite Thin Films of Fe xO y Nanoparticles and Photocrosslinked Dextran Hydrogels

    NASA Astrophysics Data System (ADS)

    Brunsen, Annette; Utech, Stefanie; Maskos, Michael; Knoll, Wolfgang; Jonas, Ulrich

    2012-04-01

    Magnetic hydrogel composites are promising candidates for a broad field of applications from medicine to mechanical engineering. Here, surface-attached composite films of magnetic nanoparticles (MNP) and a polymeric hydrogel (HG) were prepared from magnetic iron oxide nanoparticles and a carboxymethylated dextran with photoreactive benzophenone substituents. A blend of the MNP and the dextran polymer was prepared by mixing in solution, and after spin-coating and drying the blend film was converted into a stable MNP-HG composite by photocrosslinking through irradiation with UV light. The bulk composite material shows strong mobility in a magnetic field, imparted by the MNPs. By utilizing a surface layer of a photoreactive adhesion promoter on the substrates, the MNP-HG films were covalently immobilized during photocrosslinking. The high stability of the composite was documented by rinsing experiments with UV-Vis spectroscopy, while surface plasmon resonance and optical waveguide mode spectroscopy was employed to investigate the swelling behavior in dependence of the nanoparticle concentration, the particle type, and salt concentration.

  8. Crosslinked chitosan-dextran sulfate nanoparticle for improved topical ocular drug delivery

    PubMed Central

    Chaiyasan, Wanachat; Srinivas, Sangly P.

    2015-01-01

    Purpose To examine the benefits of chitosan-dextran sulfate nanoparticles (CDNs) as a topical ocular delivery system with lutein as a model drug. Methods CDNs were developed by polyelectrolyte complexation of positively charged chitosan (CS) and negatively charged dextran sulfate (DS). 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and polyethylene glycol 400 (PEG400) were used as co-crosslinking and stabilizing agents, respectively. The influence of these on the properties of CDNs, including drug release and mucoadhesiveness, was examined. The chemical stability of lutein in CDNs (LCDNs) was also examined. Results Typically, LCDNs showed a spherical shape, possessing a mean size of ~400 nm with a narrow size distribution. The entrapment efficiency of lutein was in the range of 60%–76%. LCDNs possessing a positive surface charge (+46 mV) were found to be mucoadhesive. The release profile of LCDNs followed Higuchi’s square root model, suggesting drug release by diffusion from the polymer matrix. Lutein in LCDNs showed increased chemical stability during storage compared to its solution form. Conclusions These characteristics of CDNs make them suitable for drug delivery to the ocular surface. PMID:26604662

  9. One-pot synthesis of dextran decorated reduced graphene oxide nanoparticles for targeted photo-chemotherapy.

    PubMed

    Hu, Yanfang; He, Liang; Ding, Jianxun; Sun, Diankui; Chen, Li; Chen, Xuesi

    2016-06-25

    Graphene-based nanocarriers show great potential in photo-chemotherapy, however, to prepare desired reduced graphene oxide (rGO) nanoparticles in a facile way is still a challenge. Herein, a novel strategy has been presented to prepare rGO nanoparticle using dextran (Dex) as a reducing agent. In this strategy, Dex was directly conjugated on rGO by hydrogen bond and then self-assemble to form rGO/Dex nanoparticles. After decorated by dextran, rGO-based nanoparticles not only show excellent biocompatibility but also can load anticancer drug for photo-chemotherapy. The data of fourier transform infrared (FT-IR) analysis, Raman spectrum analysis, thermos-gravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), the transmission electron microscope (TEM) image and dynamic light scattering (DLS) measurements powerfully proved that the stable rGO-based nanoparticles with desired nanosize have been successfully prepared. To verify the photo-chemotherapy, anticancer drug, doxorubicin (DOX), has been loaded on rGO/Dex nanoparticles (rGO/DOX/Dex). And RGD, a kind of oligopeptide which can improve the intracellular uptake by αvβ3 recognition, also has been introduced (rGO/DOX/RDex). Compared with single chemotherapy, rGO/DOX/Dex and rGO/DOX/RDex combining the local specific chemotherapy and external near-infrared (NIR) photo-thermal therapy show higher therapeutic efficacy, endowing the desired rGO-based nanoparticle with great potential for cancer treatments.

  10. Non-cytotoxic, In Situ Gelable Hydrogels Composed of N-carboxyethyl Chitosan and Oxidized Dextran

    PubMed Central

    Weng, Lihui; Romanov, Alexander; Rooney, Jean; Chen, Weiliam

    2008-01-01

    A series of in situ gelable hydrogels were prepared from oxidized dextran (Odex) and N-carboxyethyl chitosan (CEC) without any extraneous crosslinking agent. The gelation readily took place at physiological pH and body temperature. The gelation process was monitored rheologically, and the effect of the oxidation degree of dextran on the gelation process was investigated. The higher the oxidation degree of Odex, the faster the gelation. A highly porous hydrogel structure was revealed under scanning electron microscopy (SEM). Swelling and degradation of the Odex/CEC hydrogels in PBS showed that both swelling and degradation were related to the crosslinking density of the hydrogels. In particular, the hydrogels underwent fast mass loss in the first 2 weeks, followed by a more moderate degradation. The results of long-term cell viability tests revealed that the hydrogels were non-cytotoxic. Mouse fibroblasts were encapsulated in the hydrogels and cell viability was at least 95% within 3 days following encapsulation. Furthermore, cells entrapped inside the hydrogel assumed round shape initially but they gradually adapted to the new environment and spread out to assume more spiny shapes. Additionally, the results from applying the Odex/CEC system to mice full-thickness transcutaneous wound models suggested that it was capable of enhancing wound healing. PMID:18639926

  11. 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 ind