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Sample records for celecoxib inhibits helicobacter

  1. Celecoxib inhibits Helicobacter pylori colonization-related factors

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the effect of celecoxib,a selective COX-2 inhibitor,on Helicobacter pylori(H.pylori) colonization-related factors and its mechanism.METHODS:After co-incubation with celecoxib,morphology of H.pylori strain 26695 was observed under a transmission electron microscope.Flagella motility was assessed by stab agar motility test.Adherence of H.pylori to AGS cells was determined by enzyme linked immunosorbent assay.Levels of mRNA expression in flagellar genes(flaA,flaB),urease genes(ureA,ureB)and ...

  2. Anti- Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous lesions

    Institute of Scientific and Technical Information of China (English)

    Li-Jing Zhang; Shi-Yan Wang; Xiao-Hui Huo; Zhen-Long Zhu; Jian-Kun Chu; Jin-Cheng Ma; Dong-Sheng Cui; Ping Gu; Zeng-Ren Zhao; Ming-Wei Wang; Jun Yu

    2009-01-01

    AIM:To evaluate whether celecoxib,a selective cyclooxygenase 2 (COX-2) inhibitor,could reduce the severity of gastric precancerous lesions following Helicobacter pylori (H pylori) eradication.METHODS:H pylori-eradicated patients with gastric precancerous lesions randomly received either celecoxib (n=30) or placebo (n=30) for up to 3 mo.COX-2 expression and activity was determined by immunostaining and prostaglandin E2 (PGE2) assay,cell proliferation by Ki-67 immunostaining,apoptosis by TUNEL staining and angiogenesis by microvascular density (MVD) assay using CD31 staining.RESULTS:COX-2 protein expression was significantly increased in gastric precancerous lesions (atrophy,intestinal metaplasia and dysplasia,respectively) compared with chronic gastritis,and was concomitant with an increase in cell proliferation and angiogenesis.A significant improvement in precancerous lesions was observed in patients who received celecoxib compared with those who received placebo (P<0.001).Of these three changes,84.6% of sites with dysplasia regressed in patients treated with celecoxib (P=0.002) compared with 60% in the placebo group,suggesting that celecoxib was effective on the regression of dysplasia.COX-2 protein expression (P<0.001) and COX-2 activity (P<0.001) in the gastric tissues were consistently lower in celecoxib-treated patients compared with the placebo-treated subjects.Moreover,it was also shown that celecoxib suppressed cell proliferation (P<0.01),induced cell apoptosis (P<0.01) and inhibited angiogenesis with decreased MVD (P<0.001).However,all of these effects were not seen in placebo-treated subjects.Furthermore,COX-2 inhibition resulted in the up-regulation of PPARg expression,a protective molecule with anti-neoplastic effects.CONCLUSION:H pylori eradication therapy followed by celecoxib treatment improves gastric precancerous lesions by inhibiting COX-2 activity,inducing apoptosis,and suppressing cell proliferation and angiogenesis.

  3. Celecoxib transiently inhibits cellular protein synthesis.

    Science.gov (United States)

    Pyrko, Peter; Kardosh, Adel; Schönthal, Axel H

    2008-01-15

    To uncover the full spectrum of its pharmacological activities, the selective COX-2 inhibitor celecoxib is routinely being used at concentrations of up to 100 microM in cell culture. At these elevated concentrations, several COX-2-independent effects were identified, although many details of these events have remained unclear. Here, we report a COX-2-independent effect of celecoxib that might have profound consequences for the interpretation of previous results obtained at elevated concentrations of this drug in vitro. We found that celecoxib rapidly inhibits general protein translation at concentrations as low as 30 microM. This appears to be a consequence of endoplasmic reticulum (ER) stress and entails the phosphorylation and inactivation of eukaryotic translation initiation factor 2 alpha (eIF2alpha). These effects were not achieved by other coxibs (rofecoxib, valdecoxib) or traditional NSAIDs (indomethacin, flurbiprofen), but were mimicked by the COX-2-inactive celecoxib analog, 2,5-dimethyl-celecoxib (DMC), indicating COX-2 independence. Considering the obvious impact of blocked translation on cellular function, we provide evidence that this severe inhibition of protein synthesis might suffice to explain some of the previously reported COX-2-independent effects of celecoxib, such as the down-regulation of the essential cell cycle regulatory protein cyclin D, which is a short-lived protein that rapidly disappears in response to the inhibition of protein synthesis. Taken together, our findings establish ER stress-induced inhibition of general translation as a critical outcome of celecoxib treatment in vitro, and suggest that this effect needs to be considered when interpreting observations from the use of this drug in cell culture. PMID:17920040

  4. Inhibition of Bacterial Multidrug Resistance by Celecoxib, a Cyclooxygenase-2 Inhibitor▿

    OpenAIRE

    Kalle, Arunasree M.; Rizvi, Arshad

    2010-01-01

    Multidrug resistance (MDR) is a major problem in the treatment of infectious diseases and cancer. Accumulating evidence suggests that the cyclooxygenase-2 (COX-2)-specific inhibitor celecoxib would not only inhibit COX-2 but also help in the reversal of drug resistance in cancers by inhibiting the MDR1 efflux pump. Here, we demonstrate that celecoxib increases the sensitivity of bacteria to the antibiotics ampicillin, kanamycin, chloramphenicol, and ciprofloxacin by accumulating the drugs ins...

  5. Celecoxib Inhibits Proliferation and Induces Apoptosis via Cyclooxygen-ase-2 Pathway in Human Pancreatic Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    WU Gaosong; YI Jilin; DI Fang; ZOU Shengquan; LI Xingrui

    2005-01-01

    In order to evaluate the effects and mechanisms of celecoxib in inhibiting proliferation and inducing apoptosis on human pancreatic carcinoma cells, the anti-proliferative effect was measured by using methabenzthiazuron (MTT) assay. Cell cycle and apoptosis were analyzed by using flow cytometry (FCM), and the PGE2 levels in the supernatant of cultured pancreatic carcinoma cells were quantitated by enzyme-linked immunoabsordent assay (ELISA). Our results showed that celecoxib suppressed the production of PGE2 and inhibited the growth of JF-305 cells, and the anti-proliferative effect of celecoxib could be abolished by addition of PGE2. FCM revealed that celecoxib could inhibit proliferation and induce apoptosis by G1-S cell cycle arrest. It was concluded that cyclooxygenase-2 specific inhibitor celecoxib could inhibit proliferation and induced apoptosis of human pancreatic carcinoma cells via suppression of PGE2 production in vitro.

  6. Celecoxib in combination with retinoid CD437 inhibits melanoma A375 cell in vitro

    Institute of Scientific and Technical Information of China (English)

    Jianwen REN; Zhenhui PENG; Birong GUO; Min PAN

    2009-01-01

    This study aimed to investigate the effects of celecoxib, synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylicacid (CD437)and the combination of the two on cell proliferation, apoptosis, and cycle arrest of human malignant mela-noma A375 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazoliumbromide assay (MTT assay) was applied to determine the anti-proliferative effects of the drugs on human malignant melanoma A375 cells. Flow cytometry was performed to investigate the influence of the drugs on cell cycle and cell apoptosis. Both celecoxib and CD437 could inhibit the growth of human malignant melanoma A375 cells in a dose-dependent manner. Celecoxib at 80 μmol/L inhibited proliferation, induced apoptosis and G2/M cell cycle arrest of human malignant melanoma A375 cells after treatment for 24 h [proliferation inhibiting rate: (50.2±2.51)%, apoptosis rate: (35.91±1.80)%]. CD437 at 10μmol/L inhibited proliferation, induced apoptosis and G0/G1 cell cycle arrest of human malignant melanoma A375 cells after treatment for 24 h [proliferation inhibiting rate: (58.6±2.38)%, apoptosis rate: (28.03± 0.77)%]. Celecoxib in combination with CD437 could significantly enhance the effects of inhibiting proliferation and inducing apoptosis of human malignant melanoma A375 cells 24 h after treatment compared with the drugalone [proliferation inhibiting rate: (68.92±1.72)%, apop-tosis rate: (42.09±1.05)%, both P <0.05] and decrease the proportion of the S phase in the cell cycle. Celecoxib could inhibit the growth of human malignant melanoma A375 cells by inducing apoptosis and G2/M cycle arrest. CD437 could inhibit the growth of human malignant melanoma A375 cells by inducing apoptosis and G0/G1 cycle arrest. Celecoxib exhibited additive effects with CD437 on retarding the growth and inducing apoptosis of human malignant melanoma A375 cells. Celecoxib in combination with CD437 may become an effective method for prevention and treatment of

  7. Preoperative growth inhibition of human gastric adenocarcinoma treated with a combination of celecoxib and octreotide

    Institute of Scientific and Technical Information of China (English)

    Mao-tao HUANG; Zhi-xin CHEN; Bing WEI; Bo ZHANG; Chun-hui WANG; Ming-hui HUANG; Rui LIU; Cheng-wei TANG

    2007-01-01

    Aim:To gain insight into the histopathological responses and molecular targets in the inhibition of growth of human gastric cancer treated with celecoxib (a cyclooxygenase [COX]-2 inhibitor) combined with octreotide. Methods:Seventy five patients with gastric cancer undergoing curative gastrectomy or extended resection were randomly divided into 3 groups. The apoptosis of tumor cells was measured by terminal deoxynucleotide transferase-mediated dUTP nick endlabeling (TUNEL) assay. Gastric cancer microvessel density (MVD) and the expression of COX-2 were evaluated by immunohistochemlcal staining. The expression of somatostatin receptor (SSTR)-2 was detected with the biomolecular interaction analysis system. The transcription of non-steroidal anti-inflammatory drugactivated gene (NAG)-I was measured by RT-PCR. Results:Compared with the control and celecoxib groups,more necrosis in the combination group was observed. The apoptotic rate in the combination group (7.06%±0.67%) was sig nificantly higher than that in the control group (6.23%±1.29%,P<0.05). The MVD decreased considerably in the combination group. The upregulation of NAG-1 was displayed both in the celecoxib and combination groups. The positive rate of SSTR-2 in gastric cancers treated with celecoxib (48%) was significantly higher than that of control group (12%) after surgery (P<0.05). Conclusion:Celecoxib combined with octreotide significantly promoted necrosis in gastric adenocarcinoma through the induction of apoptosis and the reduction of MVD. NAG-1 and SSTR-2 might be the molecular targets for celecoxib or octreotide.

  8. Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats.

    Science.gov (United States)

    Gao, Jin-Hang; Wen, Shi-Lei; Feng, Shi; Yang, Wen-Juan; Lu, Yao-Yao; Tong, Huan; Liu, Rui; Tang, Shi-Hang; Huang, Zhi-Yin; Tang, Ying-Mei; Yang, Jin-Hui; Xie, Hui-Qi; Tang, Cheng-Wei

    2016-10-01

    Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro-hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)-hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK-HIF-1α-VEGF signaling pathway. PMID:27380212

  9. Cyclooxygenase-2 inhibitor, celecoxib, inhibits leiomyoma cell proliferation through the nuclear factor κB pathway.

    Science.gov (United States)

    Park, Seung Bin; Jee, Byung Chul; Kim, Seok Hyun; Cho, Yeon Jean; Han, Myoungseok

    2014-09-01

    Our aim was to investigate whether celecoxib, a cyclooxygenase 2 (COX-2) inhibitor, decreases the in vitro proliferation of leiomyoma cells if the inflammatory pathway is blocked. Menstruation is an inflammation of uterus that produces cytokines and prostanoids, but the inflammatory mechanism underlying the growth of leiomyoma remains unexplained. Using in vitro cultures of leiomyoma cells obtained from 5 patients who underwent hysterectomy, cell proliferation, inflammatory signaling, transcription factors, growth factors, and extracellular matrix were examined by (4,5-dimethylthiaxol-2-yi)-2,5-diphenyltetraxolium bromide assay, immunoblotting, and quantitative polymerase chain reaction. Prostaglandin E2 was used to induce menstruation-like condition in the cells. We found that celecoxib inhibited COX-2 through the expression of nuclear factor κB in the cells. Celcoxib also decreased the gene expression of interleukin 6, tumor necrosis factor α, collagen A, fibronectin, platelet-derived growth factor, epidermal growth factor, and transforming growth factor β. In conclusion, the present study indicated that celecoxib could inhibit leiomyoma cell proliferation through blocking the inflammatory pathway that is probably one of the mechanisms underlying its pathogenesis.

  10. COX-2 inhibition is neither necessary nor sufficient for celecoxib to suppress tumor cell proliferation and focus formation in vitro

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    Petasis Nicos A

    2008-05-01

    Full Text Available Abstract Background An increasing number of reports is challenging the notion that the antitumor potential of the selective COX-2 inhibitor celecoxib (Celebrex® is mediated primarily via the inhibition of COX-2. We have investigated this issue by applying two different analogs of celecoxib that differentially display COX-2-inhibitory activity: the first analog, called unmethylated celecoxib (UMC, inhibits COX-2 slightly more potently than its parental compound, whereas the second analog, 2,5-dimethyl-celecoxib (DMC, has lost the ability to inhibit COX-2. Results With the use of glioblastoma and pancreatic carcinoma cell lines, we comparatively analyzed the effects of celecoxib, UMC, and DMC in various short-term (≤48 hours cellular and molecular studies, as well as in long-term (≤3 months focus formation assays. We found that DMC exhibited the most potent antitumor activity; celecoxib was somewhat less effective, and UMC clearly displayed the overall weakest antitumor potential in all aspects. The differential growth-inhibitory and apoptosis-stimulatory potency of these compounds in short-term assays did not at all correlate with their capacity to inhibit COX-2, but was closely aligned with their ability to trigger endoplasmic reticulum stress (ERS, as indicated by the induction of the ERS marker CHOP/GADD153 and activation of the ERS-associated caspase 7. In addition, we found that these compounds were able to restore contact inhibition and block focus formation during long-term, chronic drug exposure of tumor cells, and this was achieved at sub-toxic concentrations in the absence of ERS or inhibition of COX-2. Conclusion The antitumor activity of celecoxib in vitro did not involve the inhibition of COX-2. Rather, the drug's ability to trigger ERS, a known effector of cell death, might provide an alternative explanation for its acute cytotoxicity. In addition, the newly discovered ability of this drug to restore contact inhibition and

  11. Inhibition of cyclooxygenase-2 activity by celecoxib does not lead to radiosensitization of human prostate cancer cells in vitro

    International Nuclear Information System (INIS)

    Purpose: To evaluate the potential radiosensitizing effect of the specific COX-2 inhibitor celecoxib (Celebrex[reg]) on prostate carcinoma cells in vitro. Materials and methods: The influence of celecoxib (concentration range 5 to 75 μM) on radiation-induced cellular and clonogenic survival was investigated in prostate carcinoma cell lines PC-3, DU145, LNCaP and normal prostate epithelial cells (PrEC). Western blot analysis and ELISA were used to determine the impact of radiation alone or radiation combined with celecoxib treatment on COX-2 expression and prostaglandin E2 synthesis. To evaluate induction of celecoxib-induced apoptosis cell cycle analysis has been performed. Results: Celecoxib (5, 10 and 25 μM) in combination with single-dose irradiation of 2 Gy induced a significant radiosensitization in normal prostate epithelial cells which could not be observed for any of the prostate carcinoma cell lines investigated. Increased COX-2 protein expression in PC-3 cells was obvious only after IR with 15 Gy, while PGE2 production was elevated following irradiation (2-15 Gy) in a dose-dependent manner. Treatment with celecoxib alone or in combination with IR led to a dose-dependent increase in COX-2 protein expression. Nevertheless pre-treatment with celecoxib caused a marked reduction of radiation-induced enzyme activity as tested at the level of PGE2 production, both in PC-3 and DU145 cells. Following fractionated irradiation with single doses of 2 Gy, elevated COX-2 protein expression as well as enhanced PGE2 production was observed already after the second fraction in PC-3 cells. Pre-treatment with celecoxib reduced the amount of PGE2 significantly, but not of COX-2 protein. Conclusions: Our data obtained for the human prostate cancer cell lines do not indicate that a marked inhibition of prostaglandin E2 synthesis by celecoxib leads to enhanced radiosensitization. Thus, in terms of radiosensitization the analysed prostate cancer cells can be classified as non

  12. Celecoxib-erlotinib combination delays growth and inhibits angiogenesis in EGFR-mutated lung cancer.

    Science.gov (United States)

    Li, Yi Xiao; Wang, Jia Le; Gao, Meng; Tang, Hao; Gui, Rong; Fu, Yun Feng

    2016-01-01

    Combination treatment for non-small cell lung cancer (NSCLC) is becoming more popular due to the anticipation that it may be more effective than single drug treatment. In addition, there are efforts to genetically screen patients for specific mutations in light of attempting to administer specific anticancer agents that are most effective. In this study, we evaluate the anticancer and anti-angiogenic effects of low dose celecoxib-erlotinib combination in NSCLC in vitro and in vivo. In NSCLC cells harboring epidermal growth factor receptor (EGFR) mutations, combination celecoxib-erlotinib treatment led to synergistic cell death, but there was minimal efficacy in NSCLC cells with wild-type EGFR. In xenograft models, combination treatment also demonstrated greater inhibition of tumor growth compared to individual treatment. The anti-tumor effect observed was secondary to the targeting of angiogenesis, evidenced by decreased vascular endothelial growth factor A (VEGFA) levels and decreased levels of CD31 and microvessel density. Combination treatment targets angiogenesis through the modulation of of the PI3K/AKT and ERK/Raf1-1 pathway in NSCLC with EGFR exon 19 deletions. These findings may have significant clinical implications in patients with tumors harboring EGFR exon 19 deletions as they may be particularly sensitive to this regimen. PMID:27508092

  13. Inhibition mechanism of the intracellular transporter Ca2+-pump from sarco-endoplasmic reticulum by the antitumor agent dimethyl-celecoxib.

    Directory of Open Access Journals (Sweden)

    Ramón Coca

    Full Text Available Dimethyl-celecoxib is a celecoxib analog that lacks the capacity as cyclo-oxygenase-2 inhibitor and therefore the life-threatening effects but retains the antineoplastic properties. The action mechanism at the molecular level is unclear. Our in vitro assays using a sarcoplasmic reticulum preparation from rabbit skeletal muscle demonstrate that dimethyl-celecoxib inhibits Ca2+-ATPase activity and ATP-dependent Ca2+ transport in a concentration-dependent manner. Celecoxib was a more potent inhibitor of Ca2+-ATPase activity than dimethyl-celecoxib, as deduced from the half-maximum effect but dimethyl-celecoxib exhibited higher inhibition potency when Ca2+ transport was evaluated. Since Ca2+ transport was more sensitive to inhibition than Ca2+-ATPase activity the drugs under study caused Ca2+/Pi uncoupling. Dimethyl-celecoxib provoked greater uncoupling and the effect was dependent on drug concentration but independent of Ca2+-pump functioning. Dimethyl-celecoxib prevented Ca2+ binding by stabilizing the inactive Ca2+-free conformation of the pump. The effect on the kinetics of phosphoenzyme accumulation and the dependence of the phosphoenzyme level on dimethyl-celecoxib concentration were independent of whether or not the Ca2+-pump was exposed to the drug in the presence of Ca2+ before phosphorylation. This provided evidence of non-preferential interaction with the Ca2+-free conformation. Likewise, the decreased phosphoenzyme level in the presence of dimethyl-celecoxib that was partially relieved by increasing Ca2+ was consistent with the mentioned effect on Ca2+ binding. The kinetics of phosphoenzyme decomposition under turnover conditions was not altered by dimethyl-celecoxib. The dual effect of the drug involves Ca2+-pump inhibition and membrane permeabilization activity. The reported data can explain the cytotoxic and anti-proliferative effects that have been attributed to the celecoxib analog. Ligand docking simulation predicts interaction of

  14. Green tea inhibits Helicobacter growth in vivo and in vitro

    OpenAIRE

    Stoicov, Calin; Saffari, Reza; Houghton, JeanMarie

    2009-01-01

    Helicobacter infection, one of the most common bacterial infections in man worldwide, is a type 1 carcinogen and the most important risk factor for gastric cancer. Helicobacter pylori bacterial factors, components of the host genetics and immune response, dietary cofactors and decreased acid secretion resulting in bacterial overgrowth are all considered important factors for induction of gastric cancer. Components found in green tea have been shown to inhibit bacterial growth, including the g...

  15. Sulfonation of 17β-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus

    International Nuclear Information System (INIS)

    The sulfonation of 17β-estradiol (E2) by human liver and recombinant sulfotransferases is influenced by environmental contaminants such as hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs), which are potent inhibitors, and the therapeutic drug, celecoxib, which affects positional sulfonation of E2. In some locations, the aquatic environment is contaminated by PCBs, OH-PCBs and widely used therapeutic drugs. The objectives of this study were to investigate the sulfonation kinetics of E2 in liver cytosol from channel catfish (Ictalurus punctatus); to examine the effect of OH-PCBs on E2 sulfonation; and to determine if celecoxib altered the position of E2 sulfonation, as it does with human liver cytosol. E2 was converted to both 3- and 17-sulfates by catfish liver cytosol. At E2 concentrations below 1μM, formation of E2-3-sulfate (E2-3-S) predominated, but substrate inhibition was observed at higher concentrations. Rates of E2-3-S formation at different E2 concentrations were fit to a substrate inhibition model, with K'm and V'max values of 0.40+/-0.10μM and 91.0+/-4.7pmol/min/mg protein, respectively and Ki of 1.08+/-0.09μM. The formation of E2-17-S fit Michaelis-Menten kinetics over the concentration range 25nM to 2.5μM, with Km and Vmax values of 1.07+/-0.23μM and 25.7+/-4.43pmol/min/mg protein, respectively. The efficiency (Vmax/Km) of formation of E2-3-S was 9.8-fold higher than that of E2-17-S. Several OH-PCBs inhibited E2 3-sulfonation, measured at an E2 concentration of 1nM. Of those tested, the most potent inhibitor was 4'-OH-CB79, with two chlorine atoms flanking the OH group (IC50: 94nM). The inhibition of estrogen sulfonation by OH-PCBs may disrupt the endocrine system and thus contribute to the known toxic effects of these compounds. Celecoxib did not stimulate E2-17-S formation, as is the case with human liver cytosol, but did inhibit the formation of E2-3-S (IC50: 44μM) and to a lesser extent, E2-17-S (IC50: >160μM), suggesting the

  16. Interferon-γ and celecoxib inhibit lung-tumor growth through modulating M2/M1 macrophage ratio in the tumor microenvironment

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    Ren F

    2014-09-01

    Full Text Available Fuqiang Ren,1,2,* Mingyu Fan,1,2,* Jiandong Mei,1,2 Yongqiang Wu,3 Chengwu Liu,1,2 Qiang Pu,1,2 Zongbing You,4–9 Lunxu Liu1,2 1Department of Thoracic Surgery, West China Hospital, 2Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, 3Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Department of Structural and Cellular Biology, 5Department of Orthopaedic Surgery, 6Tulane Cancer Center, 7Louisiana Cancer Research Consortium, 8Tulane Center for Stem Cell Research and Regenerative Medicine, 9Tulane Center for Aging, Tulane University Health Sciences Center, New Orleans, LA, USA *These two authors contributed equally to this study Abstract: Tumor-associated macrophages play an important role in tumor growth and progression. These macrophages are heterogeneous with diverse functions, eg, M1 macrophages inhibit tumor growth, whereas M2 macrophages promote tumor growth. In this study, we found that IFNγ and/or celecoxib (cyclooxygenase-2 inhibitor treatment consistently inhibited tumor growth in a mouse lung cancer model. IFNγ alone and celecoxib alone increased the percentage of M1 macrophages but decreased the percentage of M2 macrophages in the tumors, and thus the M2/M1 macrophage ratio was reduced to 1.1 and 1.7 by IFNγ alone and celecoxib alone, respectively, compared to the M2/M1 macrophage ratio of 4.4 in the control group. A combination of IFNγ and celecoxib treatment reduced the M2/M1 macrophage ratio to 0.8. Furthermore, IFNγ and/or celecoxib treatment decreased expression of matrix metalloproteinase (MMP-2, MMP-9, and VEGF, as well as the density of microvessels in the tumors, compared to the control group. This study provides the proof of principle that IFNγ and/or celecoxib treatment may inhibit lung-tumor growth through modulating the M2/M1 macrophage ratio in the tumor microenvironment, suggesting

  17. Sulfonation of 17{beta}-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus

    Energy Technology Data Exchange (ETDEWEB)

    Wang Liquan [Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610 (United States); James, Margaret O. [Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610 (United States)]. E-mail: mojames@ufl.edu

    2007-03-10

    The sulfonation of 17{beta}-estradiol (E2) by human liver and recombinant sulfotransferases is influenced by environmental contaminants such as hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs), which are potent inhibitors, and the therapeutic drug, celecoxib, which affects positional sulfonation of E2. In some locations, the aquatic environment is contaminated by PCBs, OH-PCBs and widely used therapeutic drugs. The objectives of this study were to investigate the sulfonation kinetics of E2 in liver cytosol from channel catfish (Ictalurus punctatus); to examine the effect of OH-PCBs on E2 sulfonation; and to determine if celecoxib altered the position of E2 sulfonation, as it does with human liver cytosol. E2 was converted to both 3- and 17-sulfates by catfish liver cytosol. At E2 concentrations below 1{mu}M, formation of E2-3-sulfate (E2-3-S) predominated, but substrate inhibition was observed at higher concentrations. Rates of E2-3-S formation at different E2 concentrations were fit to a substrate inhibition model, with K{sup '}{sub m} and V{sup '}{sub max} values of 0.40+/-0.10{mu}M and 91.0+/-4.7pmol/min/mg protein, respectively and K{sub i} of 1.08+/-0.09{mu}M. The formation of E2-17-S fit Michaelis-Menten kinetics over the concentration range 25nM to 2.5{mu}M, with K{sub m} and V{sub max} values of 1.07+/-0.23{mu}M and 25.7+/-4.43pmol/min/mg protein, respectively. The efficiency (V{sub max}/K{sub m}) of formation of E2-3-S was 9.8-fold higher than that of E2-17-S. Several OH-PCBs inhibited E2 3-sulfonation, measured at an E2 concentration of 1nM. Of those tested, the most potent inhibitor was 4'-OH-CB79, with two chlorine atoms flanking the OH group (IC{sub 50}: 94nM). The inhibition of estrogen sulfonation by OH-PCBs may disrupt the endocrine system and thus contribute to the known toxic effects of these compounds. Celecoxib did not stimulate E2-17-S formation, as is the case with human liver cytosol, but did inhibit the

  18. A Histone Deacetylase Inhibitor, OBP-801, and Celecoxib Synergistically Inhibit the Cell Growth with Apoptosis via a DR5-Dependent Pathway in Bladder Cancer Cells.

    Science.gov (United States)

    Toriyama, Seijiro; Horinaka, Mano; Yasuda, Shusuke; Taniguchi, Tomoyuki; Aono, Yuichi; Takamura, Toshiya; Morioka, Yukako; Miki, Tsuneharu; Ukimura, Osamu; Sakai, Toshiyuki

    2016-09-01

    The prognosis of muscle-invasive bladder cancer with metastasis is poor. There have been no therapeutic improvements for many years, and an innovative therapy for muscle-invasive bladder cancer has been awaited to replace the conventional cytotoxic chemotherapy. Here, we show a candidate method for the treatment of bladder cancer. The combined treatment with a novel histone deacetylase (HDAC) inhibitor, OBP-801, and celecoxib synergistically inhibited cell growth and markedly induced apoptosis through the caspase-dependent pathway in high-grade bladder cancer cells. Furthermore, the combined treatment induced expression of death receptor 5 (DR5). We identified that knockdown of DR5 by small interfering RNA (siRNA) significantly suppressed apoptosis by the combined treatment. Therefore, we conjectured that the apoptosis induced by OBP-801 and celecoxib is at least partially dependent on DR5. However, it was interesting that the combined treatment drastically suppressed expression of DR5 ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). These data suggest that there is no involvement of TRAIL in the induction of apoptosis by the combination, regardless of the dependence of DR5. Moreover, xenograft studies using human bladder cancer cells showed that the combined therapy suppressed tumor growth by upregulating expressions of DR5 and Bim. The inhibition of tumor growth was significantly more potent than that of each agent alone, without significant weight loss. This combination therapy provided a greater benefit than monotherapy in vitro and in vivo These data show that the combination therapy with OBP-801 and celecoxib is a potential novel therapeutic strategy for patients with muscle-invasive bladder cancer. Mol Cancer Ther; 15(9); 2066-75. ©2016 AACR. PMID:27406983

  19. Effect of Celecoxib on Apoptosis of Endometrial Carcinoma Cell

    Institute of Scientific and Technical Information of China (English)

    SHENG Xiu-jie; FANG Zhao

    2007-01-01

    Objective: To investigate the effect of Celecoxib on proliferation and apoptosis of the endometrial carcinoma cell HEC-1B and the effect on the expression of Fas and Survivin mRNA. Methods: The inhibition on the growth of human endometrial carcinoma cell HEC-1B was investigated by cell culture and MTT experiment when treated with different concentrations of Celecoxib. The cell apoptosis was detected by flow cytometry and DNA Ladder Electrophoresis. The change of the expression of Fas and Survivin mRNA after the treatment of Celecoxib was detected With RT-PCR. Results: Celecoxib could effectively inhibit the growth of HEC-1B cells and induce apoptosis. Survivin mRNA expression was decreased and Fas mRNA expression was increased after treating with Celecoxib. Conclusion: Celecoxib could inhibit HEC-1B cell proliferation and induce its apoptosis.

  20. Cell-cycle inhibition by Helicobacter pylori L-asparaginase.

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    Claudia Scotti

    Full Text Available Helicobacter pylori (H. pylori is a major human pathogen causing chronic gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. One of the mechanisms whereby it induces damage depends on its interference with proliferation of host tissues. We here describe the discovery of a novel bacterial factor able to inhibit the cell-cycle of exposed cells, both of gastric and non-gastric origin. An integrated approach was adopted to isolate and characterise the molecule from the bacterial culture filtrate produced in a protein-free medium: size-exclusion chromatography, non-reducing gel electrophoresis, mass spectrometry, mutant analysis, recombinant protein expression and enzymatic assays. L-asparaginase was identified as the factor responsible for cell-cycle inhibition of fibroblasts and gastric cell lines. Its effect on cell-cycle was confirmed by inhibitors, a knockout strain and the action of recombinant L-asparaginase on cell lines. Interference with cell-cycle in vitro depended on cell genotype and was related to the expression levels of the concurrent enzyme asparagine synthetase. Bacterial subcellular distribution of L-asparaginase was also analysed along with its immunogenicity. H. pylori L-asparaginase is a novel antigen that functions as a cell-cycle inhibitor of fibroblasts and gastric cell lines. We give evidence supporting a role in the pathogenesis of H. pylori-related diseases and discuss its potential diagnostic application.

  1. Repurposing celecoxib as a topical antimicrobial agent

    Directory of Open Access Journals (Sweden)

    Mohamed N. Seleem

    2015-07-01

    Full Text Available There is an urgent need for new antibiotics and alternative strategies to combat multidrug-resistant bacterial pathogens, which are a growing clinical issue. Repurposing existing approved drugs with known pharmacology and toxicology is an alternative strategy to accelerate antimicrobial research and development. In this study, we show that celecoxib, a marketed inhibitor of cyclooxygenase-2, exhibits broad-spectrum antimicrobial activity against Gram-positive pathogens from a variety of genera, including Staphylococcus, Streptococcus, Listeria, Bacillus, and Mycobacterium, but not against Gram-negative pathogens. However, celecoxib is active against all of the Gram-negative bacteria tested, including strains of, Acinetobacter, and Pseudomonas, when their intrinsic resistance is artificially compromised by outer membrane permeabilizing agents such as colistin. The effect of celecoxib on incorporation of radioactive precursors into macromolecules in Staphylococcus aureus was examined. The primary antimicrobial mechanism of action of celecoxib was the dose-dependent inhibition of RNA, DNA, and protein synthesis. Further, we demonstrate the in vivo efficacy of celecoxib in a methicillin-resistant S. aureus (MRSA infected Caenorhabditis elegans whole animal model. Topical application of celecoxib (1 and 2% significantly reduced the mean bacterial count in a mouse model of MRSA skin infection. Further, celecoxib decreased the levels of all inflammatory cytokines tested, including tumor necrosis factor-α, interleukin-6, interleukin-1 beta, and monocyte chemo attractant protein-1 in wounds caused by MRSA infection. Celecoxib also exhibited synergy with many conventional antimicrobials when tested against four clinical isolates of S. aureus. Collectively, these results demonstrate that celecoxib alone, or in combination with traditional antimicrobials, has a potential to use as a topical drug for the treatment of bacterial skin infections.

  2. Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Heumen, Bjorn W.H. van, E-mail: b.vanheumen@mdl.umcn.nl [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Roelofs, Hennie M.J.; Morsche, Rene H.M. te [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Marian, Brigitte [Institute of Cancer Research, Wien University, Vienna (Austria); Nagengast, Fokko M.; Peters, Wilbert H.M. [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-04-15

    Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14-17%, p < 0.01). A more pronounced decrease (23-27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: Black-Right-Pointing-Pointer Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. Black-Right-Pointing-Pointer UDCA enriched 'artificial bile' decreases LT-97 cell growth only in presence of celecoxib. Black-Right-Pointing-Pointer PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.

  3. Inhibition of Helicobacter pylori and Its Associate Urease by Labdane Diterpenoids Isolated from Andrographis paniculata.

    Science.gov (United States)

    Shaikh, Rafik U; Dawane, Ashwini A; Pawar, Rajendra P; Gond, Dhananjay S; Meshram, Rohan J; Gacche, Rajesh N

    2016-03-01

    The present study was carried out to evaluate anti-Helicobacter pylori and its associated urease activity of labdane diterpenoids isolated from Andrographis paniculata. A molecular docking analysis was performed by using ArgusLab 4.0.1 software. The results obtained indicate that compound A possesses strong inhibition to H. pylori, 28 ± 2.98 (minimum inhibitory concentration, 9 µg/mL), and its urease, 85.54 ± 2.62% (IC50 , 20.2 µg/mL). Compounds B, C, and D also showed moderate inhibition to H. pylori and its urease. The obtained results were in agreement with the molecular docking analysis of compounds. The phytochemicals under investigation were found to be promising antibacterial agents. Moreover, the isolated compounds can be considered as a resource for searching novel anti-H. pylori agents possessing urease inhibition. PMID:26648323

  4. Inhibition of Helicobacter pylori and Its Associate Urease by Labdane Diterpenoids Isolated from Andrographis paniculata.

    Science.gov (United States)

    Shaikh, Rafik U; Dawane, Ashwini A; Pawar, Rajendra P; Gond, Dhananjay S; Meshram, Rohan J; Gacche, Rajesh N

    2016-03-01

    The present study was carried out to evaluate anti-Helicobacter pylori and its associated urease activity of labdane diterpenoids isolated from Andrographis paniculata. A molecular docking analysis was performed by using ArgusLab 4.0.1 software. The results obtained indicate that compound A possesses strong inhibition to H. pylori, 28 ± 2.98 (minimum inhibitory concentration, 9 µg/mL), and its urease, 85.54 ± 2.62% (IC50 , 20.2 µg/mL). Compounds B, C, and D also showed moderate inhibition to H. pylori and its urease. The obtained results were in agreement with the molecular docking analysis of compounds. The phytochemicals under investigation were found to be promising antibacterial agents. Moreover, the isolated compounds can be considered as a resource for searching novel anti-H. pylori agents possessing urease inhibition.

  5. Preparation of polylactide-co-glycolide nanoparticles incorporating celecoxib and their antitumor activity against brain tumor cells

    Directory of Open Access Journals (Sweden)

    Jung S.

    2011-10-01

    Full Text Available Tae-Ho Kim1*, Young-Il Jeong2*, Shu-Guang Jin2, Jian Pei2, Tae-Young Jung1, Kyung-Sub Moon1, In-Young Kim1, Sam-Suk Kang1, Shin Jung1,21Department of Neurosurgery, 2Brain Tumor Research Laboratory, Chonnam National University Research Institute of Medical Science, Chonnam National University Hwasun Hospital and Medical School, Gwangju, Republic of Korea *These authors contributed equally to this work. Background: Celecoxib, a cyclo-oxygenase (COX-2 inhibitor, has been reported to mediate growth inhibitory effects and to induce apoptosis in various cancer cell lines. In this study, we examined the potential effects of celecoxib on glioma cell proliferation, migration, and inhibition of COX-2 expression in vitro. Methods: Celecoxib was incorporated into poly DL-lactide-co-glycolide (PLGA nanoparticles for antitumor drug delivery. Results: PLGA nanoparticles incorporating celecoxib had spherical shapes and their particle sizes were in the range of 50–200 nm. Drug-loading efficiency was not significantly changed according to the solvent used, except for acetone. Celecoxib was released from the PLGA nanoparticles for more than 2 days, and the higher the drug content, the longer the duration of drug release. PLGA nanoparticles incorporating celecoxib showed cytotoxicity against U87MG tumor cells similar to that of celecoxib administered alone. Furthermore, celecoxib did not affect the degree of migration of U87MG cells. PLGA nanoparticles incorporating celecoxib showed dose-dependent cytotoxicity similar to that of celecoxib alone in C6 rat glioma cells. Western blot assay of the C6 cells showed that neither celecoxib alone nor PLGA nanoparticles incorporating celecoxib affected COX-2 expression. Conclusion: PLGA nanoparticles incorporating celecoxib had antitumor activity similar to that of celecoxib alone, even though these particles did not affect the degree of migration or COX-2 expression in the tumor cells. Keywords: celecoxib, cyclo

  6. Evening primrose oil and celecoxib inhibited pathological angiogenesis, inflammation, and oxidative stress in adjuvant-induced arthritis: novel role of angiopoietin-1.

    Science.gov (United States)

    El-Sayed, R M; Moustafa, Y M; El-Azab, M F

    2014-10-01

    Rheumatoid arthritis is a chronic inflammatory disease characterized by overproduction of inflammatory mediators along with undermined oxidative defensive mechanisms. Pathological angiogenesis was found to play a critical role in the progression of this disease. The current study was carried out to evaluate the anti-angiogenic, anti-inflammatory, and anti-oxidant effects of evening primrose oil (EPO), rich in gamma linolenic acid (GLA), either alone or in combination with aspirin or celecoxib, on adjuvant-induced arthritis. Arthritis was induced by subcutaneous injection of complete Freund's adjuvant (CFA) in the right hind paw of male albino rats. All treatments were administered orally from day 0 (EPO, 5 g/kg b.w.) or day 4 (celecoxib, 5 mg/kg; aspirin, 150 mg/kg) till day 27 after CFA injection. In the arthritic group, the results revealed significant decrease in the body weight and increase in ankle circumference, plasma angiopoietin-1 (ANG-1) and tumor necrosis factor-alpha (TNF-α) levels. Anti-oxidant status was suppressed as manifested by significant decline in reduced glutathione content along with decreased enzymatic activity of superoxide dismutase and increased lipid peroxidation. Oral administration of EPO exerted normalization of body weight, ANG-1, and TNF-α levels with restoration of activity as shown by reduced malondialdehyde levels. Moreover, histopathological examination demonstrated that EPO significantly reduced the synovial hyperplasia and inflammatory cells invasion in joint tissues, an effect that was enhanced by combination with aspirin or celecoxib. The joint use of GLA-rich natural oils, which possess anti-angiogenic, anti-inflammatory, and anti-oxidant activities, with traditional analgesics represents a promising strategy to restrain the progression of rheumatoid arthritis.

  7. Effects of celecoxib on proliferation and tenocytic differentiation of tendon-derived stem cells

    International Nuclear Information System (INIS)

    Highlights: • Celecoxib has no effects on TDSCs cell proliferation in various concentrations. • Celecoxib reduced mRNAs levels of tendon associated transcription factor. • Celecoxib reduced mRNAs levels of main tendon associated collagen. • Celecoxib reduced mRNAs levels of tendon associated molecules. - Abstract: NSAIDs are often ingested to reduce the pain and improve regeneration of tendon after tendon injury. Although the effects of NSAIDs in tendon healing have been reported, the data and conclusions are not consistent. Recently, tendon-derived stem cells (TDSCs) have been isolated from tendon tissues and has been suggested involved in tendon repair. Our study aims to determine the effects of COX-2 inhibitor (celecoxib) on the proliferation and tenocytic differentiation of TDSCs. TDSCs were isolated from mice Achilles tendon and exposed to celecoxib. Cell proliferation rate was investigated at various concentrations (0.1, 1, 10 and 100 μg/ml) of celecoxib by using hemocytometer. The mRNA expression of tendon associated transcription factors, tendon associated collagens and tendon associated molecules were determined by reverse transcription-polymerase chain reaction. The protein expression of Collagen I, Collagen III, Scleraxis and Tenomodulin were determined by Western blotting. The results showed that celecoxib has no effects on TDSCs cell proliferation in various concentrations (p > 0.05). The levels of most tendon associated transcription factors, tendon associated collagens and tendon associated molecules genes expression were significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). Collagen I, Collagen III, Scleraxis and Tenomodulin protein expression were also significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). In conclusion, celecoxib inhibits tenocytic differentiation of tendon-derived stem cells but has no effects on cell proliferation

  8. Effects of celecoxib on proliferation and tenocytic differentiation of tendon-derived stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Kairui; Zhang, Sheng [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Li, Qianqian [Cancer Research Institute, Southern Medical University, Guangzhou 510515 (China); Yang, Jun [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Department of Orthopaedics, 421 Hospital of PLA, Guangzhou 510318 (China); Dong, Weiqiang [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Department of Orthopaedics, The First Affiliated Hospital to Guangzhou Medical University, Guangzhou 510120 (China); Wang, Shengnan; Cheng, Yirong; Al-Qwbani, Mohammed [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Wang, Qiang, E-mail: 1780468505@qq.com [Department of Orthopaedics, Subei People’s Hospital of Jiangsu Province (Clinical Medical College of Yangzhou University), Yangzhou, Jiangsu Province 225001 (China); Yu, Bin, E-mail: carryzhang1985@live.com [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China)

    2014-07-18

    Highlights: • Celecoxib has no effects on TDSCs cell proliferation in various concentrations. • Celecoxib reduced mRNAs levels of tendon associated transcription factor. • Celecoxib reduced mRNAs levels of main tendon associated collagen. • Celecoxib reduced mRNAs levels of tendon associated molecules. - Abstract: NSAIDs are often ingested to reduce the pain and improve regeneration of tendon after tendon injury. Although the effects of NSAIDs in tendon healing have been reported, the data and conclusions are not consistent. Recently, tendon-derived stem cells (TDSCs) have been isolated from tendon tissues and has been suggested involved in tendon repair. Our study aims to determine the effects of COX-2 inhibitor (celecoxib) on the proliferation and tenocytic differentiation of TDSCs. TDSCs were isolated from mice Achilles tendon and exposed to celecoxib. Cell proliferation rate was investigated at various concentrations (0.1, 1, 10 and 100 μg/ml) of celecoxib by using hemocytometer. The mRNA expression of tendon associated transcription factors, tendon associated collagens and tendon associated molecules were determined by reverse transcription-polymerase chain reaction. The protein expression of Collagen I, Collagen III, Scleraxis and Tenomodulin were determined by Western blotting. The results showed that celecoxib has no effects on TDSCs cell proliferation in various concentrations (p > 0.05). The levels of most tendon associated transcription factors, tendon associated collagens and tendon associated molecules genes expression were significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). Collagen I, Collagen III, Scleraxis and Tenomodulin protein expression were also significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). In conclusion, celecoxib inhibits tenocytic differentiation of tendon-derived stem cells but has no effects on cell proliferation.

  9. Celecoxib attenuates 5-fluorouracil-induced apoptosis in HCT-15 and HT-29 human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yun Jeong Lim; Jong Chul Rhee; Young Mee Bae; Wan Joo Chun

    2007-01-01

    AIM: To investigate the combined chemotherapeutic effects of celecoxib when used with 5-FU in vitro.METHODS: Two human colon cancer cell lines (HCT-15and HT-29) were treated with 5-FU and celecoxib, alone and in combination. The effects of each drug were evaluated using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, flow cytometry,and western blotting.RESULTS: 5-FU and celecoxib showed a dosedependent cytotoxic effect. When treated with 10-3mol/L 5-FU (IC50) and celecoxib with its concentration ranging from 10-8 mol/L to 10-4 mol/L of celecoxib,cells showed reduced cytotoxic effect than 5-FU(10-3 mol/L) alone. Flow cytometry showed that celecoxib attenuated 5-FU induced accumulation of cells at subG1 phase. Western blot analyses for caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage showed that celecoxib attenuated 5-FU induced apoptosis. Western blot analyses for cell cycle molecules showed that G2/M arrest might be possible cause of 5-FU induced apoptosis and celecoxib attenuated 5-FU induced apoptosis via blocking of cell cycle progression to the G2/M phase,causing an accumulation of cells at the G1/S phase.CONCLUSION: We found that celecoxib attenuated cytotoxic effect of 5-FU. Celecoxib might act via inhibition of cell cycle progression, thus preventing apoptosis induced by 5-FU.

  10. Natural product juglone targets three key enzymes from Helicobacter pylori: inhibition assay with crystal structure characterization

    Institute of Scientific and Technical Information of China (English)

    Yun-hua KONG; Liang ZHANG; Zheng-yi YANG; Cong HAN; Li-hong HU; Hua-liang JIANG; Xu SHEN

    2008-01-01

    Aim: To investigate the inhibition features of the natural product juglone (5-hydroxy-1,4-naphthoquinone) against the three key enzymes from Helicobacter pylori (cystathionine γ-synthase [HpCGS], malonyl-CoA:acyl carrier protein transacylase [HpFabD], and β-hydroxyacyl-ACP dehydratase [HpFabZ]). Methods: An enzyme inhibition assay against HpCGS was carded out by using a continuous coupled spectrophotometric assay approach. The inhibition assay of HpFabD was performed based on the α-ketoglutarate dehydrogenase-coupled system, while the inhibition assay for HpFabZ was monitored by detecting the decrease in absorbance at 260 nm with crotonoyl-CoA conversion to βhydroxybutyryl-CoA. The juglone/FabZ complex crystal was obtained by soaking juglone into the HpFabZ crystal, and the X-ray crystal structure of the complex was analyzed by molecular replacement approach. Results: Juglone was shown to potently inhibit HpCGS, HpFabD, and HpFabZ with the half maximal inhibitory concentration IC50 values of 7.0±0.7, 20±1, and 30±4 μmol/L, respectively. An inhibition-type study indicated that juglone was a non-competitive inhibitor of HpCGS against O-succi-nyl-L-homoserine (KI=αKI=24 μmol/L), an uncompetitive inhibitor of HpFabD against malonyl-CoA (αKI=7.4 μmol/L), and a competitive inhibitor of HpFabZ against crotonoyl-CoA (K,1=6.8 μtmol/L). Moreover, the crystal structure of the HpFabZ/juglone complex further revealed the essential binding pattern ofjuglone against HpFabZ at the atomic level. Conclusion: HpCGS, HpFabD, and HpFabZ are potential targets ofjuglone.

  11. Lactobacilli Reduce Helicobacter pylori Attachment to Host Gastric Epithelial Cells by Inhibiting Adhesion Gene Expression.

    Science.gov (United States)

    de Klerk, Nele; Maudsdotter, Lisa; Gebreegziabher, Hanna; Saroj, Sunil D; Eriksson, Beatrice; Eriksson, Olaspers Sara; Roos, Stefan; Lindén, Sara; Sjölinder, Hong; Jonsson, Ann-Beth

    2016-05-01

    The human gastrointestinal tract, including the harsh environment of the stomach, harbors a large variety of bacteria, of which Lactobacillus species are prominent members. The molecular mechanisms by which species of lactobacilli interfere with pathogen colonization are not fully characterized. In this study, we aimed to study the effect of lactobacillus strains upon the initial attachment of Helicobacter pylori to host cells. Here we report a novel mechanism by which lactobacilli inhibit adherence of the gastric pathogen H. pylori In a screen with Lactobacillus isolates, we found that only a few could reduce adherence of H. pylori to gastric epithelial cells. Decreased attachment was not due to competition for space or to lactobacillus-mediated killing of the pathogen. Instead, we show that lactobacilli act on H. pylori directly by an effector molecule that is released into the medium. This effector molecule acts on H. pylori by inhibiting expression of the adhesin-encoding gene sabA Finally, we verified that inhibitory lactobacilli reduced H. pylori colonization in an in vivo model. In conclusion, certain Lactobacillus strains affect pathogen adherence by inhibiting sabA expression and thereby reducing H. pylori binding capacity.

  12. Lactobacillus plantarum B7 inhibits Helicobacter pylori growth and attenuates gastric inflammation

    Institute of Scientific and Technical Information of China (English)

    Chompoonut Sunanliganon; Duangporn Thong-Ngam; Somying Tumwasorn; Naruemon Klaikeaw

    2012-01-01

    AIM:To determine the anti-Helicobacter property of Lactobacillus plantarum B7 (L.plantarum) B7 supernatants in vitro and the protective effects of L.plantarum B7 on serum tumor necrosis factor-alpha (TNF-α),gastric malondialdehyde (MDA) level,apoptosis,and histopathology in Helicobacter pylori (H.pylorl)-induced gastric inflammation in rats.METHODS:In vitro,the inhibition of H,pylori growth was examined using L.plantarum B7 supernatants at pH 4 and pH 7 and at the concentration of 1×,5× and 10× on plates inoculated with H.pylori.The inhibitory effect of H.pylori was interpreted by the size of the inhibition zone.In vitro,male Sprague-Dawley rats were randomly divided into four groups including group 1 (control group),group 2 (H.pylori infected group),group 3 (H.pylori infected with L.plantarum B7 10é CFUs/mL treated group) and group 4 (H.pylori infected with L.plantarum B7 1010 CFUs/mL treated group).One week after H.pylori inoculation,L.plantarum B7 106 CFUs/mL or 1010 CFUs/mL were fed once daily to group 3 and group 4,respectively,for one week.Blood and gastric samples were collected at the end of the study.RESULTS:In vitro,at intact pH 4,mean inhibitory zone diameters of 8.5 mm and 13 mm were noted at concentrations of 5× and 10× of L.plantarum B7supernatant disks,respectively.At adjusted pH 7,L.plantarum B7 supernatants at concentrations of 5 × and 10× yielded mean inhibitory zone diameters of 6.5 mm and 11 mm,respectively.In the in vitro study,in group 2,stomach histopathology revealed mild to moderate H.pylori colonization and inflammation.The level of gastric MDA and epithelial cell apoptosis were significantly increased compared with group 1.The serum TNF-α level was significant decreased in group 3compared with group 2 (P < 0.05).In addition,L.plantarum B7 treatments resulted in a significant improvement in stomach pathology,and decreased gastric MDA level and apoptotic epithelial cells.CONCLUSION:L.plantarum B7 supernatant inhibits H

  13. Celecoxib sensitizes Staphylococcus aureus to antibiotics in macrophages by modulating SIRT1.

    Directory of Open Access Journals (Sweden)

    Madhavi Annamanedi

    Full Text Available We have previously shown that celecoxib in combination with an antibiotic, increase the bacterial sensitivity to antibiotics. However, the underlying molecular mechanism remained elusive. Efficacy of the combinatorial treatment of celecoxib and ampicillin in vitro was evaluated on macrophage-phagocytosed S. aureus. To elucidate the mechanism, signaling pathway of infection and inflammation involving TLR2, JNK, SIRT1 and NF-κB was studied by FACS, Western blot, ELISA and activity assays. Combinatorial treatment of ampicillin and celecoxib reduced the bacterial load in the macrophages. Further studies clearly suggested the activation of the master regulator of oxidative stress and inflammation SIRT1, by celecoxib when used alone and/or in combination with ampicillin. Also, the results indicated that celecoxib inhibited JNK phosphorylation thereby stabilizing and activating SIRT1 protein that inhibited the COX-2 gene transcription with a significant decrease in the levels of protein inflammatory cytokines like IL-6, MIP-1α and IL-1β via inhibition of NF-κB. SIRT1 activation by celecoxib also resulted in increase of catalase and peroxidase activity with a decrease in Nitric oxide levels. In conclusion, we demonstrate a novel role of celecoxib in controlling inflammation as an enhancer of antibiotic activity against bacteria by modulating SIRT1.

  14. In vitro inhibition of Helicobacter pylori urease with non and semi fermented Camellia sinensis

    Directory of Open Access Journals (Sweden)

    Shoae Hassani A

    2009-01-01

    Full Text Available Purpose: Helicobacter pylori is the etiological agent in duodenal and peptic ulcers. The growing problem of antibiotic resistance by the organism demands the search for novel compounds, especially from natural sources. This study was conducted to evaluate the effect of Camellia sinensis extracts on the urease enzyme that is a major colonization factor for H. pylori. Methods: Minimum inhibitory concentrations of nonfermented and semifermented C. sinensis methanol: water extracts were assessed by broth dilution method. Examination of the urease function was performed by Mc Laren method, and urease production was detected on 12% SDS polyacrylamide gel electrophoresis from whole cell and membrane bound proteins. Results: Both extracts had inhibitory effects against H. pylori and urease production. At a concentration of 2.5 mg/ml of nonfermented extract and 3.5 mg/ml of semifermented extract the production of Ure A and Ure B subunits of the urease enzyme were inhibited completely. A concentration of 4 mg/ml of nonfermented and 5.5 mg/ml of semifermented extract were bactericidal for H. pylori. Conclusions: C. sinensis extracts, especially the nonfermented, could reduce H. pylori population and inhibit urease production at lower concentrations. The superior effect of nonfermented extract is due to its rich polyphenolic compounds and catechin contents.

  15. Structural Basis for the Inhibition of Helicobacter pylori α-Carbonic Anhydrase by Sulfonamides.

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    Joyanta K Modak

    Full Text Available Periplasmic α-carbonic anhydrase of Helicobacter pylori (HpαCA, an oncogenic bacterium in the human stomach, is essential for its acclimation to low pH. It catalyses the conversion of carbon dioxide to bicarbonate using Zn(II as the cofactor. In H. pylori, Neisseria spp., Brucella suis and Streptococcus pneumoniae this enzyme is the target for sulfonamide antibacterial agents. We present structural analysis correlated with inhibition data, on the complexes of HpαCA with two pharmacological inhibitors of human carbonic anhydrases, acetazolamide and methazolamide. This analysis reveals that two sulfonamide oxygen atoms of the inhibitors are positioned proximal to the putative location of the oxygens of the CO2 substrate in the Michaelis complex, whilst the zinc-coordinating sulfonamide nitrogen occupies the position of the catalytic water molecule. The structures are consistent with acetazolamide acting as site-directed, nanomolar inhibitors of the enzyme by mimicking its reaction transition state. Additionally, inhibitor binding provides insights into the channel for substrate entry and product exit. This analysis has implications for the structure-based design of inhibitors of bacterial carbonic anhydrases.

  16. Effects of celecoxib and ibuprofen on metabolic disorders induced by Walker-256 tumor in rats.

    Science.gov (United States)

    de Souza, Camila Oliveira; Kurauti, Mirian Ayumi; de Fatima Silva, Flaviane; de Morais, Hely; Borba-Murad, Glaucia Regina; de Andrade, Fábio Goulart; de Souza, Helenir Medri

    2015-01-01

    The contribution of anti-inflammatory property of celecoxib in the improvement of metabolic disorders in cancer is unknown. The purpose of this study was to compare the effects of celecoxib and ibuprofen, non-steroidal anti-inflammatory drugs (NSAIDs), on several metabolic changes observed in Walker-256 tumor-bearing rats. The effects of these NSAIDs on the tumor growth were also assessed. Celecoxib or ibuprofen (both at 25 mg/Kg) was administered orally for 12 days, beginning on the day the rats were inoculated with Walker-256 tumor cells. Celecoxib treatment prevented the losses in body mass and mass of retroperitoneal adipose tissue, gastrocnemius, and extensor digitorum longus muscles in tumor-bearing rats. Celecoxib also prevented the rise in blood levels of triacylglycerol, urea, and lactate, the inhibition of peripheral response to insulin and hepatic glycolysis, and tended to attenuate the decrease in the food intake, but had no effect on the reduction of glycemia induced by the tumor. In addition, celecoxib treatment increased the number of Walker-256 cells with signs of apoptosis and the tumor necrosis area and prevented the tumor growth. In contrast, ibuprofen treatment had no effect on metabolic parameters affected by the Walker-256 tumor or tumor growth. It can be concluded that celecoxib, unlike ibuprofen, ameliorated several metabolic changes in rats with Walker-256 tumor due to its anti-tumor effect and not its anti-inflammatory property.

  17. Antitumor activity of the selective cyclooxygenase-2 inhibitor, celecoxib, on breast cancer in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Dai Zhi-Jun

    2012-12-01

    Full Text Available Abstract Background Cyclooxygenase-2(COX-2 promotes carcinogenesis, tumor proliferation, angiogenesis, prevention of apoptosis, and immunosuppression. Meanwhile, COX-2 over-expression has been associated with tumor behavior and prognosis in several cancers. This study investigated the antitumor effects of the selective COX-2 inhibitor, Celecoxib, on breast cancer in vitro and in vivo. Methods Human breast cancer MCF-7 and MDA-MB-231 cells were cultured with different concentration (10, 20, 40 μmol/L of celecoxib after 0-96 hours in vitro. MTT assay was used to determine the growth inhibition of breast cancer cells in vitro. The expression of COX-2 on mRNA was measured by real-time quantitive PCR analysis. Flow cytometry was performed to analyze the cell cycle of MCF-7 cells. Levels of PGE2 were measured by ELISA method. The in vivo therapeutic effects of celecoxib were determined using rat breast cancer chemically induced by 7,12-dimethylben anthracene (DMBA. Results The inhibition of proliferation of both MCF-7 and MDA-MB-231 cells in vitro by celecoxib was observerd in time and dose dependent manner. Celecoxib effectively down-regulated the expression of COX-2. The cell cycle was arrested at G0/G1, and rate of cells in S phase was obviously decreased. Levels of PGE2 were inhibited by Celecoxib. The tumor incidence rate of the celecoxib group was lower than that of the control group. In addition, the tumor latency period of the celecoxib group was longer than that of the control group. Conclusions Celecoxib inhibited the proliferation of breast cancer cell lines in vitro, and prevented the occurrence of rat breast cancer chemically induced by DMBA. Therefore, celecoxib exhibits an antitumor activity and seems to be effective in anti-tumor therapy.

  18. Inhibitory effect of celecoxib combined with cisplatin on growth of human tongue squamous carcinoma Tca8113 cell xenograft tumor

    Institute of Scientific and Technical Information of China (English)

    Weizhong Li; Xiaoyan Wang; Zuguo Li; Yanqing Ding

    2010-01-01

    Objective:The aim of this study was to observe the inhibitory effect of application of COX-2 inhibitor,celecoxib,combined with cisplatin on the growth of human tongue squamous carcinoma Tca8113 cell xenograft by animal experiment.Methods:The nude mice were transplanted subcutaneously with Tca 8113 cells,and then were administrated with celecoxib,cisplatin or celecoxib combined with cisplatin respectively,and were sacrificed after 35 days.The weight of xenograft was measured to calculate the tumor inhibition rate.The histological change was studied under light and electron microscope.The COX-2 protein expression was observed by immunohistological staining.And the COX-2 mRNA expression was determined by RT-PCR.Results:Celecoxib,the COX-2 inhibitor,could not only inhibit the growth of Tca8113 cell xenograft tumor and COX-2 protein expression,but also enhance the inhibitory effect cisplatin on xenograft tumor growth significantly.The tumor inhibition rates of celecoxib group,cisplatin group and celecoxib plus cisplatin group were 15.63%,37.50% and 82.81%respectively that was statistically significant compared to control group(P < 0.01).The combined application of celecoxib and dsplatin could inhibit tumor growth more significantly than that of separated application(P < 0.01).The inhibitory effect of celecoxib on COX-2 mRNA expression of Tca 8113 cell was weaker and not significant(P= 0.073).Conclusion:Celecoxib can not only inhibit xenograft tumor growth in nude mice,but also enhance the inhibitory effect of CDDP on Tca 8113 trans planted tumor growth in nude mice.The mechanism maybe related to inhibition of COX-2 protein expression,which offers beneficial reference to further explore the mechanism between inhibition of COX-2 enzyme activity and prevention of head and neck tumor.

  19. Rectosigmoid colon venous malformation successfully treated with propranolol and celecoxib

    Directory of Open Access Journals (Sweden)

    Takanari Abematsu

    2015-08-01

    Full Text Available The pathogenesis of venous malformation needs to be clarified and, although various treatment modalities are available, an optimal treatment has not been established. A 19-year-old girl presented with venous malformation of the rectosigmoid colon. She showed severe anemia due to rectal hemorrhage; her hemoglobin (Hb level was 4.9 g/dl. A large venous malformation connected to an internal hemorrhoid was evident by endoscopy. Neither surgical resection nor sclerotherapy was indicated because of high blood flow in the venous malformation. Octreotide was initiated. However, the bleeding continued and she required persistent blood transfusions. We started propranolol in the 5th week of hospitalization. Celecoxib, which was started for her knee pain was found to be predictably effective, and we administered it regularly. Propranolol and celecoxib were gradually increased, the rectal bleeding decreased, and her anemia improved. Five months after the initiation of propranolol and celecoxib, she could maintain Hb at 15 g/dl without transfusion. Propranolol can contract blood vessels and celecoxib can inhibit vascular endothelial growth factor (VEGF to result in anti-angiogenesis. This combination therapy might be useful for controlling intractable venous malformation.

  20. Effects of Cetuximab Combined with Celecoxib on Apoptosis and KDR and AQP1 
Expression in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Honggang XIA

    2013-12-01

    Full Text Available Background and objective Neoadjuvant chemotherapy is a new development in the treatment of lung cancer. In recent years, cetuximab and celecoxib have been commonly used in this procedure. This study aims to explore the effect of cetuximab combined with celecoxib on apoptosis and KDR and AQP1 expression in lung cancer A549 cells. Method The cells were cultured in RPMI-1640 and then divided into four groups: control group, 1 nmol/L cetuximab group, 25 µmol/L celecoxib group, and 1 nmol/L cetuximab+25 µmol/L celecoxib group. The treatment time was 48 h. The mRNA and protein expression levels of KDR and AQP1 were detected by RT-PCR and Western blot, respectively. The apoptosis, proliferation, and invasive ability of A549 cells before and after transfection were examined using flow cytometry, MTT, and transwell methods. Results Cetuximab and celecoxib inhibited the growth of A549 cells in a dose-dependent manner. Their combination produced a greater growth inhibition than when either was used alone (P<0.01. Cetuximab and celecoxib both induced the apoptosis of A549 cells, and their combination produced a higher apoptosis rate (P<0.01. Cetuximab in combination with celecoxib also induced G1 phase arrest and downregulated the expression of KDR and AQP1 in A549 cells (P<0.05. As a result, the invasion ability of the A549 cells was significantly decreased. Conclusion Cetuximab in combination with celecoxib can synergistically inhibit the growth of A549 cells and downregulate the expression of KDR and AQP1 in A549 cells. The combination of cetuximab and celecoxib is a potential strategy for lung cancer therapy.

  1. Inhibition of cathepsin X enzyme influences the immune response of THP-1 cells and dendritic cells infected with Helicobacter pylori

    International Nuclear Information System (INIS)

    The immune response to Helicobacter pylori importantly determines the outcome of infection as well as the success of eradication therapy. We demonstrate the role of a cysteine protease cathepsin X in the immune response to H. pylori infection. We analysed how the inhibition of cathepsin X influenced the immune response in experiments when THP-1 cells or dendritic cells isolated from patients were stimulated with 48 strains of H. pylori isolated from gastric biopsy samples of patients which had problems with the eradication of bacteria. The experiments, performed with the help of a flow cytometer, showed that the expression of Toll-like receptors (TLRs), especially TLR-4 molecules, on the membranes of THP-1 cells or dendritic cells was higher when we stimulated cells with H. pylori together with inhibitor of cathepsin X 2F12 compared to THP-1 cells or dendritic cells stimulated with H. pylori only, and also in comparison with negative control samples. We also demonstrated that when we inhibited the action of cathepsin X in THP-1 cells, the concentrations of pro-inflammatory cytokines were lower than when THP-1 cell were stimulated with H. pylori only. We demonstrated that inhibition of cathepsin X influences the internalization of TLR-2 and TLR-4. TLR-2 and TLR-4 redistribution to intra-cytoplasmic compartments is hampered if cathepsin X is blocked. The beginning of a successful immune response against H. pylori in the case of inhibition of cathepsin X is delayed

  2. Helicobacter pylori CagA Inhibits PAR1-MARK Family Kinases by Mimicking Host Substrates

    Energy Technology Data Exchange (ETDEWEB)

    Nesic, D.; Miller, M; Quinkert, Z; Stein, M; Chait, B; Stebbins, C

    2010-01-01

    The CagA protein of Helicobacter pylori interacts with numerous cellular factors and is associated with increased virulence and risk of gastric carcinoma. We present here the cocrystal structure of a subdomain of CagA with the human kinase PAR1b/MARK2, revealing that a CagA peptide mimics substrates of this kinase family, resembling eukaryotic protein kinase inhibitors. Mutagenesis of conserved residues central to this interaction renders CagA inactive as an inhibitor of MARK2.

  3. Inhibition of Helicobacter pylori adhesion to Kato III cells by intact and low molecular weight acharan sulfate.

    Science.gov (United States)

    Sim, Joon-Soo; Hahn, Bum-Soo; Im, A-Rang; Park, Youmie; Shin, Ji-Eun; Bae, Eun-Ah; Kim, Dong-Hyun; Kim, Yeong Shik

    2011-08-01

    We investigated the inhibitory activity of glycosaminoglycans (GAGs) in terms of growth, adhesion, and VacA vacuolation of Helicobacter pylori. Intact acharan sulfate (AS, MW:114 kDa) potently inhibited H. pylori adhesion to Kato III cells with IC(50) value of 1.4 mg/mL, while other GAGs did not show any inhibitory activity except for heparin which is a well-known inhibitor of H. pylori adhesion. To investigate whether low molecular weight acharan sulfate (LMWAS) can inhibit H. pylori adhesion, we performed chemical depolymerization of AS by radical reactions to obtain LMWAS. Its physicochemical properties were characterized by high-performance size exclusion chromatography (HPSEC), agarose gel electrophoresis, disaccharide compositional analysis after digestion with heparinase II, and (1)H-NMR spectroscopy. The most potent molecular size of LMWAS was 3 kDa with IC(50) value of 32 μg/mL, which is 44-fold more potent than intact AS. These results suggest that AS as well as other GAGs can be chemically depolymerized by free radicals and LMWAS compared to intact AS can be applied as a pharmaceutical candidate in order to inhibit H. pylori adhesion to Kato III cells. PMID:21744069

  4. Formation of celecoxib nanoparticles from volatile microemulsions.

    Science.gov (United States)

    Margulis-Goshen, Katrin; Kesselman, Ellina; Danino, Dganit; Magdassi, Shlomo

    2010-06-30

    A new composition of a fully water-dilutable microemulsion system stabilized by natural surfactants is presented as a template for preparation of celecoxib nanoparticles. Nanoparticles are obtained as a dry powder upon rapid conversion of microemulsion droplets with dissolved celecoxib into nanoparticles, followed by evaporation of all the liquid in a spray dryer. The resultant powder is easily re-dispersible in water to form a clear, transparent dispersion. The celecoxib nanoparticles are amorphous and their average size in the dispersion is 17 nm, in agreement with cryo-TEM results and concentration measurements after filtration. As a result of the nanometric size and amorphous state, about 10-fold increase in dissolution of the powder was obtained, compared to that for particulate celecoxib in the presence of surfactants. PMID:20403417

  5. Celecoxib Enhances the Radiosensitizing Effect of 7-Hydroxystaurosporine (UCN-01) in Human Lung Cancer Cell Lines

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young-Mee; Jeong, In-Hye [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Pyo, Hongryull, E-mail: Quasar93@yahoo.co.kr [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-07-01

    Purpose: 7-Hydroxystaurosporine (UCN-01), a Chk1-specific inhibitor, showed promising in vitro and in vivo chemo- or radiosensitizing activity. However, there have been concerns about its limited therapeutic efficacy and risk of side effects. A method of enhancing the treatment efficacy of UCN-01 while not increasing its side effects on normal tissue may therefore be required to apply this drug in clinical settings. Celecoxib is a cyclooxygenase-2 (COX-2)-specific inhibitor that downregulates ataxia telangiectasia and rad3-related (ATR) protein, an upstream kinase of Chk1. In this study, we investigated whether the addition of celecoxib can potentiate the radiosensitizing effect of UCN-01. Methods and Materials: The cooperative radiosensitizing effects and the underlying molecular mechanisms of UCN-01 plus celecoxib were determined by clonogenic assay, tumor growth delay assay, flow cytometry, and Western blotting. Synergism of the three agents combined (UCN-01 plus celecoxib plus radiation) were evaluated using median drug effect analysis and drug-independent action model analysis. Results: The combination of UCN-01 and celecoxib could induce synergistic cytotoxicity and radiosensitizing effects in in vitro and in vivo systems. The combination of both drugs also cooperatively inhibited IR-induced G{sub 2}/M arrest, and increased the G{sub 2} to mitotic transition. Conclusions: Combined treatment with UCN-01 and celecoxib can exert synergistically enhanced radiosensitizing effects via cooperative inhibition of the ionizing radiation-activated G{sub 2} checkpoint. We propose that this combination strategy may be useful in clinical applications of UCN-01 for radiotherapy of cancer patients.

  6. Curcumin inhibits gastric inflammation induced by Helicobacter pylori infection in a mouse model.

    Science.gov (United States)

    Santos, António M; Lopes, Teresa; Oleastro, Mónica; Gato, Inês Vale; Floch, Pauline; Benejat, Lucie; Chaves, Paula; Pereira, Teresa; Seixas, Elsa; Machado, Jorge; Guerreiro, António S

    2015-01-01

    Helicobacter pylori (H. pylori) infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT) and quantitative real-time polymerase chain reaction (PCR). Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs) and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available. PMID:25569625

  7. Curcumin Inhibits Gastric Inflammation Induced by Helicobacter Pylori Infection in a Mouse Model

    Directory of Open Access Journals (Sweden)

    António M. Santos

    2015-01-01

    Full Text Available Helicobacter pylori (H. pylori infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT and quantitative real-time polymerase chain reaction (PCR. Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available.

  8. Catechin-based procyanidins from Peumus boldus Mol. aqueous extract inhibit Helicobacter pylori urease and adherence to adenocarcinoma gastric cells.

    Science.gov (United States)

    Pastene, Edgar; Parada, Víctor; Avello, Marcia; Ruiz, Antonieta; García, Apolinaria

    2014-11-01

    In this work, the anti-Helicobacter pylori effect of an aqueous extract from dried leaves of Peumus boldus Mol. (Monimiaceae) was evaluated. This extract displayed high inhibitory activity against H. pylori urease. Therefore, in order to clarify the type of substances responsible for such effect, a bioassay-guided fractionation strategy was carried out. The active compounds in the fractions were characterized through different chromatographic methods (RP-HPLC; HILIC-HPLC). The fraction named F5 (mDP = 7.8) from aqueous extract was the most active against H. pylori urease with an IC50  = 15.9 µg gallic acid equivalents (GAE)/mL. HPLC analysis evidenced that F5 was composed mainly by catechin-derived proanthocyanidins (LC-MS and phloroglucinolysis). The anti-adherent effect of boldo was assessed by co-culture of H. pylori and AGS cells. Both the aqueous extract and F5 showed an anti-adherent effect in a concentration-dependent manner. An 89.3% of inhibition was reached at 2.0 mg GAE/mL of boldo extract. In conjunction, our results suggest that boldo extract has a potent anti-urease activity and anti-adherent effect against H. pylori, properties directly linked with the presence of catechin-derived proanthocyanidins. PMID:24853276

  9. Celecoxib

    Science.gov (United States)

    ... is used to relieve pain, tenderness, swelling and stiffness caused by osteoarthritis (arthritis caused by a breakdown ... case of overdose, call your local poison control center at 1-800-222-1222. If the victim ...

  10. Lactobacilli inhibit interleukin-8 production induced by Helicobacter pylori lipopolysaccharide-activated Toll-like receptor 4

    Institute of Scientific and Technical Information of China (English)

    Chao Zhou; Feng-Zhen Ma; Xue-Jie Deng; Hong Yuan; Hong-Sheng Ma

    2008-01-01

    AIM: To investigate the effect of Lactobacillus bulgaricus (LBG) on the Toll-like receptor 4 (TLR4) pathway and interleukin-8 (IL-8) production in SGC-7901 cells treated with Helicobacter pyloriSydney strain 1 lipopolysaccharide (H pyloriSS1-LPS).METHODS: SGC-7901 cells were treated with H pyIoriSS1-LPS in the presence or absence of pretreatment for 1 h with viable LBG or supematant recovered from LBG culture MRS broth (LBG-s). Cellular lysates were prepared for Western blot with anti-TLR4,anti-transforming growth factor β-activated kinase 1 (TAK1), anti-phospho-TAK1, anti-nuclear factor κB (NF-κB), anti-p38 mitogen-activated protein kinase (p38MAPK), and anti-phospho-p38MAPK antibodies.The amount of IL-8 in cell culture medium was measured by ELISA.RESULTS: H pyloriSS1-LPS up-regulated the expression of TLR4, stimulated the phosphorylation of TAK1, subsequently enhanced the activation of NFκB and the phosphorylation of p38MAPK in a timedependent manner, leading to augmentation of IL-8 production in SGC-7901 cells. Viable LBG or LBG-s pretreatment attenuated the expression of TLR4,inhibited the phosphorylation of TAK1 and p38MAPK,prevented the activation of NF-κB, and consequently blocked IL-8 production.CONCLUSION: H pyloriSS1-LPS induces IL-8production through activating TLR4 signaling in SGC-7901 cells and viable LBG or LBG-s prevents H pyloriSS1-LPS-mediated IL-8 production via inhibition of the TLR4 pathway.

  11. BET Inhibition Attenuates Helicobacter pylori-Induced Inflammatory Response by Suppressing Inflammatory Gene Transcription and Enhancer Activation.

    Science.gov (United States)

    Chen, Jinjing; Wang, Zhen; Hu, Xiangming; Chen, Ruichuan; Romero-Gallo, Judith; Peek, Richard M; Chen, Lin-Feng

    2016-05-15

    Helicobacter pylori infection causes chronic gastritis and peptic ulceration. H. pylori-initiated chronic gastritis is characterized by enhanced expression of many NF-κB-regulated inflammatory cytokines. Brd4 has emerged as an important NF-κB regulator and regulates the expression of many NF-κB-dependent inflammatory genes. In this study, we demonstrated that Brd4 was not only actively involved in H. pylori-induced inflammatory gene mRNA transcription but also H. pylori-induced inflammatory gene enhancer RNA (eRNA) synthesis. Suppression of H. pylori-induced eRNA synthesis impaired H. pylori-induced mRNA synthesis. Furthermore, H. pylori stimulated NF-κB-dependent recruitment of Brd4 to the promoters and enhancers of inflammatory genes to facilitate the RNA polymerase II-mediated eRNA and mRNA synthesis. Inhibition of Brd4 by JQ1 attenuated H. pylori-induced eRNA and mRNA synthesis for a subset of NF-κB-dependent inflammatory genes. JQ1 also inhibited H. pylori-induced interaction between Brd4 and RelA and the recruitment of Brd4 and RNA polymerase II to the promoters and enhancers of inflammatory genes. Finally, we demonstrated that JQ1 suppressed inflammatory gene expression, inflammation, and cell proliferation in H. pylori-infected mice. These studies highlight the importance of Brd4 in H. pylori-induced inflammatory gene expression and suggest that Brd4 could be a potential therapeutic target for the treatment of H. pylori-triggered inflammatory diseases and cancer. PMID:27084101

  12. Synergistic analgesia of duloxetine and celecoxib in the mouse formalin test: a combination analysis.

    Directory of Open Access Journals (Sweden)

    Yong-Hai Sun

    Full Text Available Duloxetine, a serotonin and noradrenaline reuptake inhibitor, and celecoxib, a non-steroidal anti-inflammatory drug, are commonly used analgesics for persistent pain, however with moderate gastrointestinal side effects or analgesia tolerance. One promising analgesic strategy is to give a combined prescription, allowing the maximal or equal efficacy with fewer side effects. In the current study, the efficacy and side effects of combined administration of duloxetine and celecoxib were tested in the mouse formalin pain model. The subcutaneous (s.c. injection of formalin into the left hindpaw induced significant somatic and emotional pain evaluated by the biphasic spontaneous flinching of the injected hindpaw and interphase ultrasonic vocalizations (USVs during the 1 h after formalin injection, respectively. Pretreatment with intraperitoneal (i.p. injection of duloxetine or celecoxib at 1 h before formalin injection induced the dose-dependent inhibition on the second but not first phase pain responses. Combined administration of duloxetine and celecoxib showed significant analgesia for the second phase pain responses. Combination analgesia on the first phase was observed only with higher dose combination. A statistical difference between the theoretical and experimental ED50 for the second phase pain responses was observed, which indicated synergistic interaction of the two drugs. Concerning the emotional pain responses revealed with USVs, we assumed that the antinociceptive effects were almost completely derived from duloxetine, since celecoxib was ineffective when administered alone or reduced the dosage of duloxetine when given in combination. Based on the above findings, acute concomitant administration of duloxetine and celecoxib showed synergism on the somatic pain behavior but not emotional pain behaviors.

  13. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    International Nuclear Information System (INIS)

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity

  14. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang, E-mail: lvguoqiangwuxivip@163.com

    2015-08-07

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity.

  15. Celecoxib Treatment Alters p53 and MDM2 Expression via COX-2 Crosstalk in A549 Cells.

    Science.gov (United States)

    Gharghabi, Mehdi; Rezaei, Farhang; Mir Mohammadrezaei, Fereshteh; Ghahremani, Mohammad Hossein

    2016-01-01

    Cyclooxygenase-2 (COX-2) has a pivotal role in the pathogenesis of the lung cancer. It is known that COX-2 negatively regulates the activity of a number of tumor suppressors, including p53. Consequently, inhibition of COX-2 signaling is anticipated to be a promising approach to stabilize p53 functionality. In this regard, we investigated the effect of COX-2 signaling blockade on p53 and COX-2expression in A549 cells. Cell viability was assessed using MTT and protein expression was measured using Western Blot assay. Results revealed that Celecoxib dose-dependently induced growth inhibition within 24 h. However, prolonged exposure to the drug up to 48 h led to increase cell viability compared to the corresponding control. Western blot analysis demonstrated that Celecoxib could augment p53 expression within 24 h, independently of COX-2 inhibition. In contrast, Celecoxib treatment not only returned p53 to the control level, but also strikingly induced COX-2 expression within 48 h. Of further relevance, Celecoxib exposure could significantly result in MDM2 elevation at 48 h. These findings represent p53 as a molecular target being interconnected with COX-2 signaling axis upon Celecoxib treatment. Moreover, our data point toward the possibility that Celecoxib treatment may not be a proper therapeutic strategy in lung cancer cells owing to its potential role in the activation of oncogenes, including COX-2 and MDM2 which seemingly confers a chemoresistance circumstance to the cell. Consequently, these results underscore intensive preclinical assessment prior to applying COX-2 inhibitors in the treatment of lung tumors. PMID:27642319

  16. Downregulation of survivin expression and concomitant induction of apoptosis by celecoxib and its non-cyclooxygenase-2-inhibitory analog, dimethyl-celecoxib (DMC, in tumor cells in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Hofman Florence M

    2006-05-01

    Full Text Available Abstract Background 2,5-Dimethyl-celecoxib (DMC is a close structural analog of the selective cyclooxygenase-2 (COX-2 inhibitor celecoxib (Celebrex® that lacks COX-2-inhibitory function. However, despite its inability to block COX-2 activity, DMC is able to potently mimic the anti-tumor effects of celecoxib in vitro and in vivo, indicating that both of these drugs are able to involve targets other than COX-2 to exert their recognized cytotoxic effects. However, the molecular components that are involved in mediating these drugs' apoptosis-stimulatory consequences are incompletely understood. Results We present evidence that celecoxib and DMC are able to down-regulate the expression of survivin, an anti-apoptotic protein that is highly expressed in tumor cells and known to confer resistance of such cells to anti-cancer treatments. Suppression of survivin is specific to these two drugs, as other coxibs (valdecoxib, rofecoxib or traditional NSAIDs (flurbiprofen, indomethacin, sulindac do not affect survivin expression at similar concentrations. The extent of survivin down-regulation by celecoxib and DMC in different tumor cell lines is somewhat variable, but closely correlates with the degree of drug-induced growth inhibition and apoptosis. When combined with irinotecan, a widely used anticancer drug, celecoxib and DMC greatly enhance the cytotoxic effects of this drug, in keeping with a model that suppression of survivin may be beneficial to sensitize cancer cells to chemotherapy. Remarkably, these effects are not restricted to in vitro conditions, but also take place in tumors from drug-treated animals, where both drugs similarly repress survivin, induce apoptosis, and inhibit tumor growth in vivo. Conclusion In consideration of survivin's recognized role as a custodian of tumor cell survival, our results suggest that celecoxib and DMC might exert their cytotoxic anti-tumor effects at least in part via the down-regulation of survivin – in a

  17. Helicobacter pylori

    OpenAIRE

    Bateson, M

    2000-01-01

    Helicobacter pylori infection is a major cause of peptic ulcer disease, and its detection and eradication are now an important part of gastroenterology. Effective regimes are available which will eliminate the organism in about 90% of cases in developed countries.


Keywords: Helicobacter pylori

  18. Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Jin-Hang Gao

    Full Text Available BACKGROUND: Increased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2 in the cirrhotic liver might be a potential target to ameliorate portal hypertension. OBJECTIVE: To verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. METHODS: Cirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA. 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF, VEGF receptor-2 (VEGFR-2 and related signal molecules were quantitated. RESULTS: Compared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, p<0.01. Celecoxib treatment greatly reduced the tortuous hepatic portal venules. The data of fibrotic areas, CD31expression, mRNA levels of α-SMA and collagen III in TAA+celecoxib group were much lower than those in TAA group, p<0.01. Furthermore, the up-regulation of hepatic mRNA and protein levels of VEGF, VEGFR-2 and COX-2 induced by TAA was significantly inhibited after celecoxib treatment. The expressions of prostaglandin E2 (PGE2, phosphorylated extracellular signal-regulated kinase (p-ERK, hypoxia-inducible factor-1α (HIF-1α, and c-fos were also down-regulated after celecoxib treatment. CONCLUSIONS: Long term administration of celecoxib can efficiently ameliorate portal hypertension in TAA rat model by its dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. The anti-angiogenesis effect afforded by celecoxib may attribute to its

  19. A multi-epitope vaccine CTB-UE relieves Helicobacter pylori-induced gastric inflammatory reaction via up-regulating microRNA-155 to inhibit Th17 response in C57/BL6 mice model

    OpenAIRE

    Lv, Xiaobo; Song, Hui; Yang, Jue; Li, Tong; Xi, Tao; Xing, Yingying

    2014-01-01

    Vaccination is an effective mean of preventing infectious diseases, including those caused by Helicobacter pylori. Th17 cell responses are critical for the pathogenesis of Helicobacter pylori infection. In view of Th17 responses to multi-epitope vaccine CTB-UE, the IL-17 production in antiserum was examined. CTB-UE immunization decreased IL-17 production, implying that Th17 responses may be inhibited. Furthermore, IL-17 aggravated GES-1 cell injury induced by H. pylori SS1; In contrast, CTB-U...

  20. ENHANCING SOLUBILITY AND DISSOLUTION OF CELECOXIB BY SPRAY DRYING TECHNIQUE

    OpenAIRE

    Dixit Mudit; Kulkarni Parthasarathi Keshavarao; Panner Selvam; Jain Achin

    2012-01-01

    Celecoxib, a selective COX-2 inhibitor, exhibits poor water solubility, dissolution and flow properties. Thus, the aim of the present study was to improve the solubility and dissolution rate of celecoxib by preparing crystals by spray drying technique using pluronic F 127. Celecoxib crystals were produced by spray drying using TBA and water as co-solvent system to enhance solubility and dissolution rate. The prepared crystals were evaluated for solubility and in-vitro dissolution. The prepare...

  1. HELICOBACTER PYLORI

    Science.gov (United States)

    Helicobacter pylori is a pathogenic bacteria which inhabits the human stomach and upper gastrointestinal tract. This encyclopedic entry summarizes the potential role of this organism as a waterborne pathogen. Information is provided on the physiology and morphology of this bacter...

  2. Effects of Celecoxib and Ly117018 Combination on Human Breast Cancer Cells in Vitro

    Directory of Open Access Journals (Sweden)

    Klaus H. Baumann

    2009-01-01

    Full Text Available Activation and signalling of estrogen receptor (ER and COX-2 represent two important pathways in breast cancer cell regulation. Activation of either pathway is associated with breast cancer cell proliferation and eventually malignant progression. Raloxifene analogue, Ly117018, a selective estrogen receptor modulator and celecoxib, a specific COX- 2 inhibitor have been shown to inhibit breast cancer cell proliferation when used alone in vitro and in vivo. In this study, the combined drug effects on hormone-dependent MCF-7 and hormone-independent MDA-MB-435 cells in vitro were evaluated. Cell proliferation assays excluded drug antagonism and revealed a moderate synergistic growth inhibitory activity of Ly117018 and celecoxib on both cell lines when combined in specific concentrations. Growth inhibition of either compound was not associated with cell cycle arrest. In MCF-7 cells, western blot analysis revealed a decreased phosphorylation of the AKT protein by either agent alone or in combination. In MDA-MB-435 cells, celecoxib alone induced an increase in AKT phosphorylation relative to total AKT protein; this effect was decreased in the presence of Ly117018. These results indicate that these two drugs are non-antagonistic; and when combined in specific concentrations, moderate synergistic antiproliferative activity of celecoxib and Ly117018 were observed in hormone-dependent MCF-7 and hormone- independent MDA-MB-435 cells associated with changes in cell cycle distribution and regulation of AKT protein and phosphorylation. These findings further support a central role of the ER- and COX-2 pathways in human breast cancer cells.

  3. Acetylated Rhamnogalacturonans from Immature Fruits of Abelmoschus esculentus Inhibit the Adhesion of Helicobacter pylori to Human Gastric Cells by Interaction with Outer Membrane Proteins

    Directory of Open Access Journals (Sweden)

    Christian Thöle

    2015-09-01

    Full Text Available Polysaccharide containing extracts from immature fruits of okra (Abelmoschus esculentus are known to exhibit antiadhesive effects against bacterial adhesion of Helicobacter pylori (H. pylori to stomach tissue. The present study investigates structural and functional features of polymers responsible for this inhibition of bacterial attachment to host cells. Ammonium sulfate precipitation of an aqueous extract yielded two fractions at 60% and 90% saturation with significant antiadhesive effects against H. pylori, strain J99, (FE60% 68% ± 15%; FE90% 75% ± 11% inhibition rates after preincubation of the bacteria at 1 mg/mL. Sequential extraction of okra fruits yielded hot buffer soluble solids (HBSS with dose dependent antiadhesive effects against strain J99 and three clinical isolates. Preincubation of H. pylori with HBSS (1 mg/mL led to reduced binding to 3ʹ-sialyl lactose, sialylated Lea and Lex. A reduction of bacterial binding to ligands complementary to BabA and SabA was observed when bacteria were pretreated with FE90%. Structural analysis of the antiadhesive polysaccharides (molecular weight, monomer composition, linkage analysis, stereochemistry, and acetylation indicated the presence of acetylated rhamnogalacturonan-I polymers, decorated with short galactose side chains. Deacetylation of HBSS and FE90% resulted in loss of the antiadhesive activity, indicating esterification being a prerequisite for antiadhesive activity.

  4. α-Lipoic Acid Inhibits Helicobacter pylori-Induced Oncogene Expression and Hyperproliferation by Suppressing the Activation of NADPH Oxidase in Gastric Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Eunyoung Byun

    2014-01-01

    Full Text Available Hyperproliferation and oncogene expression are observed in the mucosa of Helicobacter pylori- (H. pylori- infected patients with gastritis or adenocarcinoma. Expression of oncogenes such as β-catenin and c-myc is related to oxidative stress. α-Lipoic acid (α-LA, a naturally occurring thiol compound, acts as an antioxidant and has an anticancer effect. The aim of this study is to investigate the effect of α-LA on H. pylori-induced hyperproliferation and oncogene expression in gastric epithelial AGS cells by determining cell proliferation (viable cell numbers, thymidine incorporation, levels of reactive oxygen species (ROS, NADPH oxidase activation (enzyme activity, subcellular levels of NADPH oxidase subunits, activation of redox-sensitive transcription factors (NF-κB, AP-1, expression of oncogenes (β-catenin, c-myc, and nuclear localization of β-catenin. Furthermore, we examined whether NADPH oxidase mediates oncogene expression and hyperproliferation in H. pylori-infected AGS cells using treatment of diphenyleneiodonium (DPI, an inhibitor of NADPH oxidase. As a result, α-LA inhibited the activation of NADPH oxidase and, thus, reduced ROS production, resulting in inhibition on activation of NF-κB and AP-1, induction of oncogenes, nuclear translocation of β-catenin, and hyperproliferation in H. pylori-infected AGS cells. DPI inhibited H. pylori-induced activation of NF-κB and AP-1, oncogene expression and hyperproliferation by reducing ROS levels in AGS cells. In conclusion, we propose that inhibiting NADPH oxidase by α-LA could prevent oncogene expression and hyperproliferation occurring in H. pylori-infected gastric epithelial cells.

  5. Evaluation of 2 celecoxib derivatives: analgesic effect and selectivity to cyclooxygenase-2/1

    Institute of Scientific and Technical Information of China (English)

    Zhi-hong LU; Xiao-yun XIONG; Bang-le ZHANG; Guo-cheng LIN; Yu-xiang SHI; Zhen-guo LIU; Jing-ru MENG; Yu-mei ZHOU; Qi-bing MEI

    2005-01-01

    Aim: To evaluate the analgesic effects of 2 celecoxib derivatives and their inhibitory effects on cyclooxygenase (COX). Methods: Four antinociceptive assays were used: the acetic acid-induced writhing test, hot plate test, hot tail-flick test and formalin test. Three doses were used in the analgesic assays and ED50 values were calculated. For the selectivity assay, macrophages were incubated with test compounds at various concentrations and then stimulated with calcimycin or lipopolysaccharide (LPS). The amounts of 6-keto-prostaglandin F1α (6-keto-PGF1α)and prostaglandin E2 (PGE2) in the supernatant were examined by radioimmunoassay (RIA). The selectivity of the test compounds was expressed as the IC50,COX-1/IC50,COX-2 value. Results: Celecoxib and its 2 derivatives had a significant analgesic effect. The ED50 values of celecoxib, PC-406 and PC-407 were 94.2, 67.9, and 63.3mg/kg, respectively, for the acetic acid-induced writhing test; 104.7, 89.1, and 30.0mg/kg, respectively, for the hot tail-flick response test; 60.7, 56.7, and 86.2 mg/kg,respectively, for the hot plate response test; 67.1,55.8, and 68.8 mg/kg, respectively,for the formalin-induced response. That is, the ED50 of PC-406 was the lowest for the formalin and hot plate tests, which focus on changes above the spinal cord level; however, the ED50 of PC-407 was lowest for the tail-flick and writhing tests,which focus on changes at the spinal cord level. Celecoxib and PC-407 inhibited COX-1 with IC50 values of 39.8 and 27.5 nmol/L, respectively. PC-406 inhibited COX-1 with an IC50 value of more than 1000 nmol/L. The IC50 values for the effect of celecoxib, PC-406 and PC-407 on COX-2 were 4.8, 8.9, and 1.9 nmol/L respectively.The IC50,COX-1/IC50,COX-2 ratios for celecoxib and PC-407 were 8.3 and 14.4, respectively. For PC-406, the ratio was greater than 112.2. Conclusion: Derivatives of celecoxib via substitution with an isopropyl or naphthyl group at the 5 position in the pyrazole ring still have

  6. Helicobacter pylori

    DEFF Research Database (Denmark)

    Leth, Peter Mygind

    1992-01-01

    Helicobacter pylori (HP) are Gram-negative spiral bacteria which occur in the human stomach. The bacteria were cultured in vitro for the first time in 1983. It is suspected that the bacteria may cause chronic gastritis of type B and may also be a contributory cause of chronic ulceration and cancer...

  7. Neuroprotective effects of cyclooxygenase-2 inhibitor celecoxib against toxicity of LPS-stimulated macrophages toward motor neurons

    Institute of Scientific and Technical Information of China (English)

    Yong HUANG; Jing LIU; Li-zhen WANG; Wei-yu ZHANG; Xing-zu ZHU

    2005-01-01

    Aim: To establish an in vitro injured motor neuronal model and investigate the neuroprotective effects and possible mechanism of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on this model. Methods: After macrophages were stimulated with lipopolysaccharide (LPS)+interferon-γ (IFN-γ) in the presence or absence of celecoxib for 24 h, the cell-free supernatant of LPS-stimulated macrophages was transferred to the culture of NSC34 cells. Viability of NSC34cells was assessed by MTT assay after a further 24 h and 72 h incubation. After macrophages were stimulated by LPS+IFN-γ for 12 h or 24 h, the release of prostaglandin E2 (PGE2), nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1 β) from macrophages was measured by radioimmunoassay, Griess assay, fluorescence assay and enzyme-linked immunosorbent assay, respectively. The mRNA levels of COX-2, inducible nitric oxide synthase (iNOS), TNF-α and IL-1 β in macrophages were determined by reverse transcription-polymerase chain reaction after macrophages were stimulated for 6 h and 12 h. Results: The supernatant of LPS-stimulated mouse macrophages induced the death of NSC34 cells and celecoxib protected the NSC34cells against this toxicity. The LPS-induced increases in the release of PGE2, NO,TNF-o and IL-1 β from macrophages were attenuated by pre-treatment with celecoxib. However, celecoxib showed no effect on the ROS levels upregulated by LPS+IFN-γin the macrophage supernatant. The mRNA levels of COX-2, iNOS,TNF-α and IL-1β were increased in LPS-activated macrophages and, except COX-2,reduced by pre-treatment with celecoxib. Conclusion: An in vitro injured motor neuronal model was established by using the toxicity of LPS-stimulated mouse macrophages toward motor neuronal NSC34 cells. In this model, celecoxib exerted neuroprotective effects on motor neurons via an inhibition of the neurotoxic secretions from activated macrophages.

  8. ROLE OF CELECOXIB IN BENIGN BREAST DISEASE: RANDOMISED CONTROL TRIAL

    Directory of Open Access Journals (Sweden)

    Soumen Das

    2012-06-01

    Full Text Available Benign Breast Disease (BBD, commonest cause of morbidity in females due to breast diseases, still offers therapeutic challenge. Several drug therapies (with Evening Primrose Oil, Danazol etc have been tried, but none made gold standard. Reports on effect of Cox-2 inhibitors are scarce. This randomized control trial aims at determination of effect of Cox- inhibitors (Celecoxib in BBD in comparison to Evening Primrose Oil (EPO . Celecoxib showed better reduction in lump size (in 80% than EPO group (in 50%. Pain reduction was excellent in COX -2 groups as compared to EPO group. Recurrence rate was also lower in Celecoxib group at 10 weeks. Side effects were almost nil in both the groups. Celecoxib is better than EPO in the management of BBD. Short course therapy with COX-2 inhibitors gives good pain relief, greater reduction in lump size, low recurrence with minimum side effects.

  9. An extract of Pelargonium sidoides (EPs 7630) inhibits in situ adhesion of Helicobacter pylori to human stomach.

    Science.gov (United States)

    Wittschier, N; Faller, G; Hensel, A

    2007-04-01

    Root extract from Pelargonium sidoides DC is used therapeutically as antimicrobial agent against infections of the respiratory system. In order to elucidate possible modes of actions we investigated the influence of P. sidoides root extract on microbial adhesion with Helicobacter pylori as model microorganism, a germ with a strong adherence to human stomach tissue. In an in-situ anti-adhesion assay intact human stomach tissue from patient resectates was incubated with fluorescent-labelled bacteria. Epithelial adhesion occurred in untreated samples and was quantified by fluorescent microscopy. Pre-treatment of the bacteria with Pelargonium extract showed good anti-adhesive activity. The antiadhesive effect was clearly dose-dependent in a range from 0.001 to 10 mg/ml. Within agar diffusion-test the extract had no direct cytotoxicity against H. pylori. The results show that the root extract from Pelargonium sidoides is a potent anti-adhesive agent against H. pylori and could therefore be a useful choice to avoid the first step of a bacterial infection.

  10. Albumin microspheres as carriers for the antiarthritic drug celecoxib

    OpenAIRE

    Thakkar, Hetal; Sharma, Rakesh Kumar; Mishra, Anil Kumar; Chuttani, Krishna; Murthy, Rayasa Ramchandra

    2005-01-01

    The present study investigates the preparation of celecoxib-loaded albumin microspheres and the biodistribution of technetium-99m (99mTc)-labeled celecoxib as well as its microspheres after intravenous administration. Microspheres were prepared using a natural polymer BSA using emulsification chemical cross-linking method. The prepared microspheres were characterized for entrapment efficiency, particle size, and in vitro drug release. Surface morphology was studied by scanning electron micros...

  11. Antiparasitic drug nitazoxanide inhibits the pyruvate oxidoreductases of Helicobacter pylori, selected anaerobic bacteria and parasites, and Campylobacter jejuni.

    Science.gov (United States)

    Hoffman, Paul S; Sisson, Gary; Croxen, Matthew A; Welch, Kevin; Harman, W Dean; Cremades, Nunilo; Morash, Michael G

    2007-03-01

    Nitazoxanide (NTZ) exhibits broad-spectrum activity against anaerobic bacteria and parasites and the ulcer-causing pathogen Helicobacter pylori. Here we show that NTZ is a noncompetitive inhibitor (K(i), 2 to 10 microM) of the pyruvate:ferredoxin/flavodoxin oxidoreductases (PFORs) of Trichomonas vaginalis, Entamoeba histolytica, Giardia intestinalis, Clostridium difficile, Clostridium perfringens, H. pylori, and Campylobacter jejuni and is weakly active against the pyruvate dehydrogenase of Escherichia coli. To further mechanistic studies, the PFOR operon of H. pylori was cloned and overexpressed in E. coli, and the multisubunit complex was purified by ion-exchange chromatography. Pyruvate-dependent PFOR activity with NTZ, as measured by a decrease in absorbance at 418 nm (spectral shift from 418 to 351 nm), unlike the reduction of viologen dyes, did not result in the accumulation of products (acetyl coenzyme A and CO(2)) and pyruvate was not consumed in the reaction. NTZ did not displace the thiamine pyrophosphate (TPP) cofactor of PFOR, and the 351-nm absorbing form of NTZ was inactive. Optical scans and (1)H nuclear magnetic resonance analyses determined that the spectral shift (A(418) to A(351)) of NTZ was due to protonation of the anion (NTZ(-)) of the 2-amino group of the thiazole ring which could be generated with the pure compound under acidic solutions (pK(a) = 6.18). We propose that NTZ(-) intercepts PFOR at an early step in the formation of the lactyl-TPP transition intermediate, resulting in the reversal of pyruvate binding prior to decarboxylation and in coordination with proton transfer to NTZ. Thus, NTZ might be the first example of an antimicrobial that targets the "activated cofactor" of an enzymatic reaction rather than its substrate or catalytic sites, a novel mechanism that may escape mutation-based drug resistance. PMID:17158936

  12. Celecoxib enhances radiation response of secondary bone tumors of a human non-small cell lung cancer via antiangiogenesis in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Klenke, Frank Michael [Bern Univ. (Switzerland). Dept. of Orthopedic Surgery; Abdollahi, Amir [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Tufts Univ. School of Medicine, Boston, MA (United States). Center of Cancer Systems Biology; Bischof, Marc; Huber, Peter E. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Gebhard, Martha-Maria [Heidelberg Univ. (Germany). Dept. of Experimental Surgery; Ewerbeck, Volker [Heidelberg Univ. (Germany). Dept. of Orthopedic Surgery; Sckell, Axel [Charite Univ. Medical Center, Berlin (Germany). Dept. of Orthopedic, Trauma and Reconstructive Surgery

    2011-01-15

    Purpose: Cyclooxygenase-2 (COX-2) inhibitors mediate a systemic antitumor activity via antiangiogenesis and seem to enhance the response of primary tumors to radiation. Radiosensitizing effects of COX-2 inhibition have not been reported for bone metastases. Therefore, the aim of this study was the investigation of the radiosensitizing effects of the selective COX-2 inhibitor celecoxib in secondary bone tumors of a non-small cell lung carcinoma in vivo. Materials and Methods: Human A549 lung carcinomas were implanted into a cranial window preparation in male SCID mice (n = 24). Animals were treated with either celecoxib or radiation (7 Gy single photon dose) alone or a combination of celecoxib and radiation, respectively. Untreated animals served as controls. The impact of radiation and COX-2 inhibition on angiogenesis, microcirculation, and tumor growth was analyzed over 28 days by means of intravital microscopy and histological methods. Results: Monotherapies with radiation as well as celecoxib had significant antitumor effects compared to untreated controls. Both therapies reduced tumor growth and vascularization to a similar extent. The simultaneous administration of celecoxib and radiation further enhanced the antitumor and antiangiogenic effects of single-beam radiation. With the combined treatment approach, tumor vascularization and tumor size were decreased by 57% and 51%, respectively, as compared to monotherapy with radiation. Conclusion: The combined application of radiation therapy and COX-2 inhibition showed synergistic effects concerning the inhibition of tumor growth and tumor angiogenesis. Therefore, the combination of radiation with COX-2 inhibitor therapy represents a promising approach to improve the therapeutic efficacy of radiotherapy of bone metastases. (orig.)

  13. Combination of fasudil and celecoxib promotes the recovery of injured spinal cord in rats better than celecoxib or fasudil alone

    Directory of Open Access Journals (Sweden)

    Xiao-lin Hou

    2015-01-01

    Full Text Available Resistance mechanisms of rho-associated kinase (ROCK inhibitors are associated with the enhanced expression of cyclooxygenase-2 (COX-2. The therapeutic effects of ROCK on nervous system diseases might be enhanced by COX-2 inhibitors. This study investigated the synergistic effect of the combined use of the ROCK inhibitor fasudil and a COX-2 inhibitor celecoxib on spinal cord injury in a rat model established by transecting the right half of the spinal cord at T 11 . Rat models were orally administrated with celecoxib (20 mg/kg and/or intramuscularly with fasudil (10 mg/kg for 2 weeks. Results demonstrated that the combined use of celecoxib and fasudil significantly decreased COX-2 and Rho kinase II expression surrounding the lesion site in rats with spinal cord injury, improved the pathomorphology of the injured spinal cord, and promoted the recovery of motor function. Moreover, the effects of the drug combination were better than celecoxib or fasudil alone. This study demonstrated that the combined use of fasudil and celecoxib synergistically enhanced the functional recovery of injured spinal cord in rats.

  14. Combination of fasudil and celecoxib promotes the recovery of injured spinal cord in rats better than celecoxib or fasudil alone.

    Science.gov (United States)

    Hou, Xiao-Lin; Chen, Yan; Yin, Hua; Duan, Wei-Gang

    2015-11-01

    Resistance mechanisms of rho-associated kinase (ROCK) inhibitors are associated with the enhanced expression of cyclooxygenase-2 (COX-2). The therapeutic effects of ROCK on nervous system diseases might be enhanced by COX-2 inhibitors. This study investigated the synergistic effect of the combined use of the ROCK inhibitor fasudil and a COX-2 inhibitor celecoxib on spinal cord injury in a rat model established by transecting the right half of the spinal cord at T11. Rat models were orally administrated with celecoxib (20 mg/kg) and/or intramuscularly with fasudil (10 mg/kg) for 2 weeks. Results demonstrated that the combined use of celecoxib and fasudil significantly decreased COX-2 and Rho kinase II expression surrounding the lesion site in rats with spinal cord injury, improved the pathomorphology of the injured spinal cord, and promoted the recovery of motor function. Moreover, the effects of the drug combination were better than celecoxib or fasudil alone. This study demonstrated that the combined use of fasudil and celecoxib synergistically enhanced the functional recovery of injured spinal cord in rats.

  15. 幽门螺杆菌抑制大鼠乙酸胃溃疡愈合的机制%Mechanism of Helicobacter Pylori Inhibiting the Healing of Acetic Acid-Induced Gastric Ulcer in Rats

    Institute of Scientific and Technical Information of China (English)

    李成军; 夏立丁; 金丽; 王国忠

    2009-01-01

    目的 研究幽门螺杆菌抑制大鼠乙酸胃溃疡愈合的机制.方法 用幽门螺杆菌感染Wistar大鼠,4周后复制出乙酸胃溃疡模型,在溃疡模型复制后的3、8、16天测定胃窦部黏膜G细胞、D细胞的数目、胃液量和pH.结果 Hp+乙酸溃疡组G细胞数目、胃液量高于乙酸溃疡组(P<0.01);D细胞的数目和pH低于乙酸溃疡组(P<0.01).结论 幽门螺杆菌通过增加胃酸分泌抑制溃疡愈合.%Objective To study the mechanism of Helicobacter Pylori inhibiting the healing of acetic acid - induced gastric ulcer in rats. Methods Rats were infected with Helicobacter Pylori and the model of acetic acid gastric ulcer was replicated at 4 weeks after in-fection. Amount of G cell and D cell in mucosa of gastric antrum, quantity of gastric juice and pH were measured at the 3rd,Sth, 16th day after the model was replicated. Results When the group of Hp + acetic acid ulcer compared with the group of acetic acid ulcer, the number of G cell, quantity of gastric juice increased (P < 0.01), and the number of D cell and pH decreased (P < 0.01). Conclusion Helicobacter Pylori inhibits ulcer healing through increasing gastric acid secretion.

  16. Reduction of scar formation in full-thickness wounds with topical celecoxib treatment.

    Science.gov (United States)

    Wilgus, Traci A; Vodovotz, Yael; Vittadini, Elena; Clubbs, Elizabeth A; Oberyszyn, Tatiana M

    2003-01-01

    Adult wound repair occurs with an initial inflammatory response, reepithelialization, and the formation of a permanent scar. Although the inflammatory phase is often considered a necessity for successful adult wound healing, fetal healing studies have shown the ability to regenerate skin and to heal wounds in a scarless manner in the absence of inflammation. The cyclooxygenase-2 (COX-2) enzyme, a known mediator of inflammation, has been shown to contribute to a variety of inflammatory conditions and to the development of cancer in many organs. To examine the role of COX-2 in the wound healing process, incisional wounds were treated topically with the anti-inflammatory COX-2 inhibitor celecoxib. Acutely, celecoxib inhibited several parameters of inflammation in the wound site. This decrease in the early inflammatory phase of wound healing had a significant effect on later events in the wound healing process, namely a reduction in scar tissue formation, without disrupting reepithelialization or decreasing tensile strength. Our data suggest that in the absence of infection, adult wound healing is able to commence with decreased inflammation and that anti-inflammatory drugs may be used to improve the outcome of the repair process in the skin by limiting scar formation.

  17. Misidentifying helicobacters: the Helicobacter cinaedi example

    DEFF Research Database (Denmark)

    Vandamme, P.; Harrington, C.S.; Jalava, K.;

    2000-01-01

    of Helicobacter cinaedi and that Helicobacter sp. strain Mainz belongs to the same species. H. cinaedi occurs in various animal reservoirs, including hamsters, dogs, cats, rats, and foxes. Appropriate growth conditions and identification strategies will be required to establish the genuine significance......Whole-cell protein electrophoresis and biochemical examination by means of a panel of 64 tests were used to identify 14 putative helicobacters to the species level. The results were confirmed by means of DNA-DNA hybridization experiments and were used to discuss misidentification of helicobacters...... based on 16S rRNA gene sequence data. The data indicated that comparison of near-complete 16S ribosomal DNA sequences does not always provide conclusive evidence for species level identification and may prove highly misleading. The data also indicated that "Helicobacter westmeadii" is a junior synonym...

  18. 15-Hydroxyprostaglandin dehydrogenase inactivation as a mechanism of resistance to celecoxib chemoprevention of colon tumors.

    LENUS (Irish Health Repository)

    Yan, Min

    2009-06-09

    Pharmacologic inhibitors of the prostaglandin-synthesizing COX-2 oncogene prevent the development of premalignant human colon adenomas. However, resistance to treatment is common. In this study, we show that the adenoma prevention activity of the COX-2 inhibitor celecoxib requires the concomitant presence of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) tumor suppressor gene, and that loss of 15-PGDH expression imparts resistance to celecoxib\\'s anti-tumor effects. We first demonstrate that the adenoma-preventive activity of celecoxib is abrogated in mice genetically lacking 15-PGDH. In FVB mice, celecoxib prevents 85% of azoxymethane-induced tumors >1 mm in size, but is essentially inactive in preventing tumor induction in 15-PGDH-null animals. Indeed, celecoxib treated 15-PGDH null animals develop more tumors than do celecoxib naive WT mice. In parallel with the loss of tumor prevention activity, celecoxib-mediated suppression of colonic PGE(2) levels is also markedly attenuated in 15-PGDH-null versus WT mice. Finally, as predicted by the murine models, humans with low colonic 15-PGDH levels also exhibit celecoxib resistance. Specifically, in a colon adenoma prevention trial, in all cases tested, individuals who developed new adenomas while receiving celecoxib treatment were also found as having low colonic 15-PGDH levels.

  19. A multi-epitope vaccine CTB-UE relieves Helicobacter pylori-induced gastric inflammatory reaction via up-regulating microRNA-155 to inhibit Th17 response in C57/BL6 mice model.

    Science.gov (United States)

    Lv, Xiaobo; Song, Hui; Yang, Jue; Li, Tong; Xi, Tao; Xing, Yingying

    2014-01-01

    Vaccination is an effective mean of preventing infectious diseases, including those caused by Helicobacter pylori. Th17 cell responses are critical for the pathogenesis of Helicobacter pylori infection. In view of Th17 responses to multi-epitope vaccine CTB-UE, the IL-17 production in antiserum was examined. CTB-UE immunization decreased IL-17 production, implying that Th17 responses may be inhibited. Furthermore, IL-17 aggravated GES-1 cell injury induced by H. pylori SS1; In contrast, CTB-UE antiserum could alleviate this cell injury, which suggesting that CTB-UE can protect GES-1 cell infected with H. pylori SS1 by inhibiting Th17 responses. Treatment of mice with CTB-UE significantly reduced the H. pylori burden and inflammation in the stomach. On the other hand, the production of IL-17 in the stomach in H. pylori-infected mice was increased; but the production of IL-17 in the stomach was decreased after treatment with CTB-UE. Furthermore, the expression of microRNA-155 in gastric tissue was significantly up-regulated. The results suggested that CTB-UE could relieve the H. pylori-induced gastric inflammatory reaction via up-regulating microRNA-155 to inhibit Th17 responses, implying that the microRNA-155/IL-17 pathway was involved. Further study is required to elucidate the relationship between miRNA-155 and IL-17. We found that the production of IL-17 was significantly increased after the expression of miRNA-155 being down-regulated; however, the production of IL-17 was significantly decreased after the expression of miRNA-155 being upregulated. PMID:25483699

  20. Survivin基因沉默抑制胃癌MGC-803细胞增殖并增强其对塞来昔布的敏感性%Survivin gene silencing inhibits the proliferation of human gastric cancer MGC-803 cells and enhances their sensitivity to celecoxib

    Institute of Scientific and Technical Information of China (English)

    方雷; 吴海滨; 陈晓岗

    2011-01-01

    Objective To investigate the effect of small interfering RNA (siRNA)-mediated survivin knock-down on the proliferation of human gastric cancer MGC-803 cells and their sensitivity to celecoxib. Methods The siRNA against survivin was constructed and transfected into MGC-803 cells via LipofectamineTM 2000. The expression of survivin in the transfected cells was detected by RT-PCR and Western blot, and flow cytometry was used to detect the cell cycle changes. The sensitivity of the cells to celecoxib after transfection was examined using MTT assay and clonogenic assay. Results The protein and mRNA levels of survivin in MGC-803 cells were decreased significantly after siRNA transfection, which also caused cell cycle arrest in G0/G1, phase. The sensitivity of MGC-803 cells to celecoxib was significantly increased after siRNA transfection. Conclusion siRNA-mediated survivin silencing causes growth suppression of MGC-803 cells and enhances their sensitivity to celecoxib in vitro.%目的 研究Survivin基因沉默对人胃癌MGC-803细胞增殖和对化疗药物塞来昔布敏感性的影响.方法 设计合成Survivin的siRNA序列,LipofectamineTM2000转染入MGC-803细胞.采用RT-PCR和Western blotting检测Survivin在干扰后mRNA和蛋白的表达情况,利用流式细胞仪检测细胞周期.通过MTT法和细胞克隆形成试验法察Survivin基因沉默后MGC-803细胞对塞来昔布的敏感性.结果 Survivin基因沉默48 h后,MGC-803细胞的Survivin基因和蛋白表达明显降低(P<0.05).细胞周期被阻滞在G0/G1期,S期细胞数减少(P<0.05).Survivin基因沉默组细胞对塞来昔布的敏感性显著性增强(P<0.05).结论 Survivin特异性siRNA能显著沉默MGC-803细胞Survivin基因,抑制细胞增殖,并增强MGC-803细胞对塞来昔布的敏感性.

  1. Helicobacter pylori Inhibits Dendritic Cell Maturation via Interleukin-10-Mediated Activation of the Signal Transducer and Activator of Transcription 3 Pathway.

    OpenAIRE

    Rizzuti, David; Ang, Michelle; Sokollik, Christiane; Wu, Ted; Abdullah, Majd; Greenfield, Laura; Fattouh, Ramzi; Reardon, Colin; Tang, Michael; Diao, Jun; Schindler, Christian; Cattral, Mark; Jones, Nicola L

    2014-01-01

    Helicobacter pylori infects the human gastric mucosa causing a chronic infection that is the primary risk factor for gastric cancer development. Recent studies demonstrate that H. pylori promotes tolerogenic dendritic cell (DC) development indicating that this bacterium evades the host immune response. However, the signaling pathways involved in modulating DC activation during infection remain unclear. Here, we report that H. pylori infection activated the signal transducer and activator of t...

  2. Effect of Weifuchun of inhibiting inflammation of helicobacter pylori-infected GES-1 cells and NF-κB signaling pathway

    Institute of Scientific and Technical Information of China (English)

    黄宣

    2014-01-01

    Objective To study the effect of Weifuchun on inflammation of Helicobacter pylori(Hp)-infected gastric epithelial cells(GES-1)and its correlation with NF-κB signaling pathway.Methods Hp standard home-made strain(CagA+,VacA+)NCTCI 1637 infected GES-1cells were used.Weifuchun was used as intervention.Weifuchun of different concentrations(5,10,and 20μg/

  3. Dosing celecoxib in pediatric patients with juvenile rheumatoid arthritis.

    Science.gov (United States)

    Krishnaswami, Sriram; Hutmacher, Matt M; Robbins, Jeffery L; Bello, Akintunde; West, Christine; Bloom, Bradley J

    2012-08-01

    The objective was to derive dosing recommendations for the use of celecoxib in patients with juvenile rheumatoid arthritis (JRA) using pharmacokinetic (PK) and exposure-response data. PK and efficacy data from a randomized, double-blind, 12-week study of celecoxib dosed at 3 and 6 mg/kg twice a day (bid) as an investigational suspension formulation in 152 JRA patients aged 2 to 17 years, PK data from 36 adult RA patients, and relative bioavailability data in healthy adults comparing suspension or capsule sprinkles with the commercial capsule were analyzed. Typical oral clearance (L/h) values were 40% and 24% lower in patients weighing 10 and 25 kg, respectively, compared with a 70-kg patient. Longitudinal, logistic pharmacodynamic models incorporating linear effects of dose/area under the plasma concentration-time curve (AUC) over 0 to 12 hours (AUC(0-12)) suggested that the percentage of responders increased with celecoxib exposure. Systemic exposures (AUC) were similar for the suspension, capsule sprinkles, and intact capsule. Administration of a 50-mg bid capsule (or sprinkles) for patients weighing 10 to 25 kg and 100 mg bid for patients >25 kg was predicted to yield similar exposures and response rates as those observed in the JRA trial. Doses and dosage forms not studied in the JRA trial were approved based on the results of this analysis.

  4. Combination of celecoxib with percutaneous radiotherapy in patients with localised prostate cancer – a phase I study

    Directory of Open Access Journals (Sweden)

    Bamberg M

    2006-04-01

    Full Text Available Abstract Background Current approaches for the improvement of bNED for prostate cancer patients treated with radiotherapy mainly focus on dose escalation. However molecularly targeted approaches may also turn out to be of value. In this regard cyclooxygenase (COX-2 inhibitors have been shown to exert some anti-tumour activities in human prostate cancer in vivo and in vitro. Although in vitro data indicated that the combination of COX-2 inhibition and radiation was not associated with an increased toxicity, we performed a phase I trial using high dose celecoxib together with percutaneous radiation therapy. Methods In order to rule out any increases of more than 20% incidence for a given side effect level 22 patients were included in the trial. Celecoxib was given 400 mg twice daily with onset of the radiation treatment. Risk adapted radiation doses were between 70 and 74 Gy standard fractionation. RTOG based gastrointestinal (GI and genitourinary (GU acute toxicity scoring was performed weekly during radiation therapy, at six weeks after therapy and three month after completing radiation treatment. Results Generally no major increase in the level and incidence of side effects potentially caused by the combined treatment was observed. In two cases a generalised skin rash occurred which immediately resolved upon discontinuation of the drug. No grade 3 and 4 toxicity was seen. Maximal GI toxicity grade 1 and 2 was observed in 85% and 10%, respectively. In terms of GU toxicity 80 % of the patients experienced a grade 1 toxicity and 10 % had grade 2 symptoms. Conclusion The combination of irradiation to the prostate with concurrent high dose celecoxib was not associated with an increased level of side effects.

  5. Synergistic effects of celecoxib and bupropion in a model of chronic inflammation-related depression in mice.

    Directory of Open Access Journals (Sweden)

    Izaque S Maciel

    Full Text Available This study was aimed to characterize the depression-like behaviour in the classical model of chronic inflammation induced by Complete Freund's Adjuvant (CFA. Male Swiss mice received an intraplantar (i.pl. injection of CFA (50 µl/paw or vehicle. Behavioural and inflammatory responses were measured at different time-points (1 to 4 weeks, and different pharmacological tools were tested. The brain levels of IL-1β and BDNF, or COX-2 expression were also determined. CFA elicited a time-dependent edema formation and mechanical allodynia, which was accompanied by a significant increase in the immobility time in the tail suspension (TST or forced-swimming (FST depression tests. Repeated administration of the antidepressants imipramine (10 mg/kg, fluoxetine (20 mg/kg and bupropion (30 mg/kg significantly reversed depression-like behaviour induced by CFA. Predictably, the anti-inflammatory drugs dexamethasone (0.5 mg/kg, indomethacin (10 mg/kg and celecoxib (30 mg/kg markedly reduced CFA-induced edema. The oral treatment with the analgesic drugs dipyrone (30 and 300 mg/kg or pregabalin (30 mg/kg significantly reversed the mechanical allodyinia induced by CFA. Otherwise, either dipyrone or pregabalin (both 30 mg/kg did not significantly affect the paw edema or the depressive-like behaviour induced by CFA, whereas the oral treatment with dipyrone (300 mg/kg was able to reduce the immobility time in TST. Noteworthy, CFA-induced edema was reduced by bupropion (30 mg/kg, and depression behaviour was prevented by celecoxib (30 mg/kg. The co-treatment with bupropion and celecoxib (3 mg/kg each significantly inhibited both inflammation and depression elicited by CFA. The same combined treatment reduced the brain levels of IL-1β, as well as COX-2 immunopositivity, whilst it failed to affect the reduction of BDNF levels. We provide novel evidence on the relationship between chronic inflammation and depression, suggesting that combination of antidepressant and

  6. Anti-Helicobacter pylori activity and oxidative burst inhibition by the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin from Paepalanthus latipes

    Directory of Open Access Journals (Sweden)

    Rodrigo Rezende Kitagawa

    2012-02-01

    Full Text Available Helicobacter pylori is a bacterium recognized as the major cause of chronic gastritis and peptic ulcers. Infection by H. pylori induces inflammatory responses and pathological changes in the gastric microenvironment. The host Keywords: immune cells (especially neutrophils release inflammatory mediators and large 5-methoxy-3,4-dehydroxanthomegnin amounts of reactive oxygen species (ROS, which are associated with an increased Helicobacter pyloririsk of developing gastric cancer. In this study, we evaluated the anti-H. pylori and oxidative burst antioxidantactivitiesofa1,4-naphthoquinone-5-methoxy-3,4-dehydroxanthomegnin. Paepalanthus latipes The antimicrobial activity was assessed using a spectrophotometric microdilution technique, and antioxidant activity was assessed by noting the effect of 5-methoxy3,4-dehydroxanthomegnin on the neutrophil oxidative burst using luminol-and lucigenin-amplified chemiluminescence. The results showed that 5-methoxy-3,4dehydroxanthomegnin is a potent anti-H. pylori compound (MIC 64 µg/mL and MBC 128 µg/mL and a strong antioxidant. 5-Methoxy-3,4-dehydroxanthomegnin decreased luminol- and lucigenin-amplified chemiluminescence, with ED50 values of 1.58±0.09 µg/mL and 5.4±0.15 µg/mL, respectively, reflecting an inhibitory effect on the oxidative burst. These results indicate that 5-methoxy-3,4-dehydroxanthomegnin is a promising compound for the prevention and treatment of diseases caused by H. pylori infection, such as gastritis, peptic ulceration, and gastric cancer, because reactive oxygen intermediates are involved in the pathogenesis of gastric mucosal injury induced by H. pylori infections.

  7. Celecoxib-induced cholestatic liver failure requiring orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Ihab I El Hajj; Shahid M Malik; Hany R Alwakeel; Obaid S Shaikh; Eizaburo Sasatomi; Hossam M Kandil

    2009-01-01

    Selective cyclooxygenase-2 (COX-2) inhibitors are widely used due to their efficacy and good safety profile.However, recent case reports have described varying degrees of liver injuries associated with the use of COX-2 inhibitors. We report the case of a patient who developed acute cholestatic hepatitis progressing to hepatic failure requiring liver transplantation, following a 3-d course of celecoxib for treatment of generalized muscle aches and pains. The clinical presentation, the laboratory data, as well as the liver histopathology were supportive of the putative diagnosis of drug induced liver injury.

  8. Celecoxib nanosuspension: single-step fabrication using a modified nanoprecipitation method and in vivo evaluation.

    Science.gov (United States)

    Malkani, Anju; Date, Abhijit A; Hegde, Darshana

    2014-08-01

    Conventional nanoprecipitation process involves addition of water miscible organic solvent containing drug to an aqueous phase containing hydrophilic surfactants to yield drug nanosuspension. However, nanosuspensions obtained with conventional nanoprecipitation process have very low colloidal stability. The objective of the present investigation was to fabricate drug nanosuspensions with good colloidal stability using a modified nanoprecipitation method. Celecoxib, a hydrophobic anti-inflammatory agent with low oral bioavailability, was used as a model drug for this investigation. The conventional nanoprecipitation method did not result in the nanosizing of the celecoxib. Incorporation of surface active lipophiles such as Labrafil 1944 CS (oleolyl macrogol glycerides) along with hydrophilic surfactants during nanoprecipitation process could successfully nanosize the celecoxib. The particle size of the nanosuspensions was influenced by the various parameters of the nanoprecipitation process and also by the concentration of the lipophilic stabilizer. The celecoxib nanosuspension was characterized by transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction. Saturation solubility of celecoxib was dramatically improved in pH 1.2 buffer when formulated as nanosuspensions. The celecoxib nanosuspesnsion showed significantly higher in vitro dissolution rate and in vivo anti-inflammatory activity as compared to that of celecoxib-marketed formulation. PMID:25787068

  9. Can celecoxib affect P-glycoprotein-mediated drug efflux? A microPET study

    International Nuclear Information System (INIS)

    Introduction: P-glycoprotein (Pgp) is an efflux pump that protects vital organs like the brain from toxic substances, but which is also associated with therapy resistance. The anti-inflammatory drug celecoxib potentiates the efficacy of several cytostatic and neurotropic drugs that are known Pgp substrates. To clarify whether Pgp is involved in the sensitizing effect of celecoxib, we investigated in vivo whether celecoxib is a substrate of Pgp and whether it can affect the efflux activity of the pump. Methods: In control rats and in rats treated with the Pgp modulator cyclosporin A (CsA), cerebral accumulation of radiolabeled [11C]celecoxib was investigated by ex vivo biodistribution and micro-positron emission tomography imaging. In addition, the effect of unlabeled celecoxib and CsA (positive control) on the cerebral uptake of the Pgp substrate [11C]verapamil was studied. Results: [11C]Celecoxib uptake in rat brain was relatively high and homogeneously distributed. Treatment of rats with CsA only marginally increased cerebral tracer uptake, which is most likely due to reduced tracer clearance from plasma. [11C]Verapamil brain uptake was more than 10-fold higher after treatment with CsA. In contrast, a high dose of celecoxib increased cerebral [11C]verapamil uptake only twofold, which was accompanied by a similar increase in tracer concentration in plasma. Conclusions: This study shows that celecoxib is not a substrate of Pgp and does not substantially affect the Pgp-mediated efflux of [11C]verapamil. Therefore, celecoxib-induced augmentation of the efficacy of chemotherapeutic and neurotropic drugs must be due to another mechanism than modulation of Pgp-mediated drug efflux

  10. Low-dose celecoxib improves coronary function after acute myocardial ischaemia in rabbits.

    Science.gov (United States)

    Zhao, Ming; He, Xi; Zhao, Mei; Bi, Xue-Yuan; Zhang, Hong-Li; Yu, Xiao-Jiang; Liu, Jin-Jun; Li, Dong-Ling; Ma, Xin; Zang, Wei-Jin

    2012-03-01

    The role of celecoxib in cardiovascular events remains contentious. The aim of the present study was to investigate the effects of celecoxib in acute myocardial ischaemia (AMI) in rabbits in comparison with those of another non-steroidal anti-inflammatory drug, namely aspirin. Male New Zealand white rabbits were divided into four groups: (i) a sham-operated group; (ii) an AMI group, in which the left anterior descending coronary arteries were occluded for 60 min; (iii) the celecoxib + AMI group, pretreated with 3 mg/kg celecoxib, twice a day, for 3 days before AMI induction; and (iv) the aspirin + AMI group, pretreated with 12.5 mg/kg aspirin, twice a day, for 3 days before AMI induction. Haemodynamic parameters were monitored using a multichannel physiological recorder. Serum levels of creatine kinase (CK), malondialdehyde (MDA), cyclo-oxygenase-2 (COX-2), tumour necrosis factor (TNF)-α, total nitrate/nitrite (NO(x) ), nitric oxide synthase (NOS) and myocardial infarct size were determined. Changes in isometric tension of isolated coronary rings were recorded by a myograph system. Compared with the sham group, the AMI group had lower blood pressure, higher left ventricular (LV) end-diastolic pressure, depressed maximum dP/dt of LV pressure, a larger infarct size and higher CK and MDA levels. Celecoxib, but not aspirin, pretreatment significantly ameliorated these effects of AMI. Celecoxib reversed AMI-induced increases in COX-2 levels to a similar extent as aspirin. Pretreatment with celecoxib resulted in a significant reduction in TNF-α levels and an increase in NO(x) and NOS levels compared with the AMI group. The dysfunctional vasoconstriction and vasodilation of coronary arteries were ameliorated by celecoxib administration. 4. In conclusion, the experimental evidence suggests that celecoxib exerts its protective effects in a COX-independent manner. PMID:22211872

  11. Can celecoxib affect P-glycoprotein-mediated drug efflux? A microPET study

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Erik F.J. de [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen (Netherlands)], E-mail: e.f.j.de.vries@ngmb.umcg.nl; Doorduin, Janine; Vellinga, Namkje A.R.; Waarde, Aren van; Dierckx, Rudi A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen (Netherlands); Klein, Hans C. [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen (Netherlands); Department of Psychiatry, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen (Netherlands)

    2008-05-15

    Introduction: P-glycoprotein (Pgp) is an efflux pump that protects vital organs like the brain from toxic substances, but which is also associated with therapy resistance. The anti-inflammatory drug celecoxib potentiates the efficacy of several cytostatic and neurotropic drugs that are known Pgp substrates. To clarify whether Pgp is involved in the sensitizing effect of celecoxib, we investigated in vivo whether celecoxib is a substrate of Pgp and whether it can affect the efflux activity of the pump. Methods: In control rats and in rats treated with the Pgp modulator cyclosporin A (CsA), cerebral accumulation of radiolabeled [{sup 11}C]celecoxib was investigated by ex vivo biodistribution and micro-positron emission tomography imaging. In addition, the effect of unlabeled celecoxib and CsA (positive control) on the cerebral uptake of the Pgp substrate [{sup 11}C]verapamil was studied. Results: [{sup 11}C]Celecoxib uptake in rat brain was relatively high and homogeneously distributed. Treatment of rats with CsA only marginally increased cerebral tracer uptake, which is most likely due to reduced tracer clearance from plasma. [{sup 11}C]Verapamil brain uptake was more than 10-fold higher after treatment with CsA. In contrast, a high dose of celecoxib increased cerebral [{sup 11}C]verapamil uptake only twofold, which was accompanied by a similar increase in tracer concentration in plasma. Conclusions: This study shows that celecoxib is not a substrate of Pgp and does not substantially affect the Pgp-mediated efflux of [{sup 11}C]verapamil. Therefore, celecoxib-induced augmentation of the efficacy of chemotherapeutic and neurotropic drugs must be due to another mechanism than modulation of Pgp-mediated drug efflux.

  12. Celecoxib Alters the Intestinal Microbiota and Metabolome in Association with Reducing Polyp Burden.

    Science.gov (United States)

    Montrose, David C; Zhou, Xi Kathy; McNally, Erin M; Sue, Erika; Yantiss, Rhonda K; Gross, Steven S; Leve, Nitai D; Karoly, Edward D; Suen, Chen S; Ling, Lilan; Benezra, Robert; Pamer, Eric G; Dannenberg, Andrew J

    2016-09-01

    Treatment with celecoxib, a selective COX-2 inhibitor, reduces formation of premalignant adenomatous polyps in the gastrointestinal tracts of humans and mice. In addition to its chemopreventive activity, celecoxib can exhibit antimicrobial activity. Differing bacterial profiles have been found in feces from colon cancer patients compared with those of normal subjects. Moreover, preclinical studies suggest that bacteria can modulate intestinal tumorigenesis by secreting specific metabolites. In the current study, we determined whether celecoxib treatment altered the luminal microbiota and metabolome in association with reducing intestinal polyp burden in mice. Administration of celecoxib for 10 weeks markedly reduced intestinal polyp burden in APC(Min/+) mice. Treatment with celecoxib also altered select luminal bacterial populations in both APC(Min/+) and wild-type mice, including decreased Lactobacillaceae and Bifidobacteriaceae as well as increased Coriobacteriaceae Metabolomic analysis demonstrated that celecoxib caused a strong reduction in many fecal metabolites linked to carcinogenesis, including glucose, amino acids, nucleotides, and lipids. Ingenuity Pathway Analysis suggested that these changes in metabolites may contribute to reduced cell proliferation. To this end, we showed that celecoxib reduced cell proliferation in the base of normal appearing ileal and colonic crypts of APC(Min/+) mice. Consistent with this finding, lineage tracing indicated that celecoxib treatment reduced the rate at which Lgr5-positive stem cells gave rise to differentiated cell types in the crypts. Taken together, these results demonstrate that celecoxib alters the luminal microbiota and metabolome along with reducing epithelial cell proliferation in mice. We hypothesize that these actions contribute to its chemopreventive activity. Cancer Prev Res; 9(9); 721-31. ©2016 AACR. PMID:27432344

  13. Screening for helicobacter pylori

    OpenAIRE

    de Sousa, Jaime Correia; Thomas, Roger

    2006-01-01

    The aim of this review is to assess whether a screening programme for Helicobacter pylori will be both successful and cost-effective. Method: We searched the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the NHS Database of Abstracts of Reviews of Effectiveness; MEDLINE; EMBASE; SilverPlatter, Biological Abstracts and Science Citation Index-Expanded. We used the search terms Helicobacter pylori and (diagnos$ or identif$ or find$) and (syst...

  14. Management of Helicobacter pylori

    OpenAIRE

    Shiota, Seiji; Yamaoka, Yoshio

    2010-01-01

    Meta-analysis has shown that successful Helicobacter pylori eradication therapy improved atrophic gastritis and intestinal metaplasia. Moreover, successful eradication therapy against atrophic gastritis has led to the suppression of the incidence of metachronous gastric cancer. Thus, the Japanese Society for Helicobacter Research concluded that all ‘H. pylori-infected persons’ should be considered for eradication therapy, irrespective of any background diseases. Successful eradication can pre...

  15. Métodos para la identificación del Celecoxib

    OpenAIRE

    Teixeira Primo, Fabián; Fröehlich, Pedro Eduardo

    2005-01-01

    Celecoxib es un antiinflamatório no esteroidal utilizado en el tratamiento del dolor y la inflamación, asociado con la artritis y otras enfermedades. El presente trabajo tiene como objetivo la identificación de celecoxib utilizándose distintos métodos. Celecoxib fue identificado por su punto de fusión, espectrofotometría en el ultravioleta e infrarrojo, cromatografía en capa delgada y resonancia magnética nuclear, todos de acuerdo con las especificaciones internacionales. Los métodos propuest...

  16. CELECOXIB LOADED LIPOSOMES: DEVELOPMENT, CHARACTERIZATION AND IN VITRO EVALUATION

    Directory of Open Access Journals (Sweden)

    M. Yasmin Begum

    2012-01-01

    Full Text Available CLX (celecoxib is a highly hydrophobic non-steroidal anti-inflammatory drug with high plasma protein binding. We describe here the encapsulation of CLX in MLVs composed of SPC and variable amounts of cholesterol. The influence of drug – lipid ratio was studied and amount of the drug could be encapsulated was optimized. The effect of cholesterol and other process parameters were studied to obtain the liposomal vesicles with desired quality. All the prepared formulations were characterized for their physico chemical properties such as appearance, vesicle size, vesicle size distribution and percentage drug entrapment. Stability of the liposomes in terms of their drug leakage and drug retention behaviour was studied by storing the liposomal formulations under different conditions for the period of 30 days. The optimized formulation parameters and process parameters resulted the liposomes with mean vesicle diameter of 4.81μ. The maximum percentage drug entrapment was achieved with the formulation CL3 which contains the drug – lipid ratio of 1:10%W/W and the percentage drug entrapment is equal to 72.33±0.64 (%. In vitro release data showed that release profile follows zero order kinetics. Celecoxib liposomes with good stability and appreciable controlled drug release with good retention of the drug even after 24 hours were prepared successfully.

  17. The alpha-carbonic anhydrase from the thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 is highly susceptible to inhibition by sulfonamides.

    Science.gov (United States)

    Vullo, Daniela; Luca, Viviana De; Scozzafava, Andrea; Carginale, Vincenzo; Rossi, Mosè; Supuran, Claudiu T; Capasso, Clemente

    2013-03-15

    The α-carbonic anhydrase (CA, EC 4.2.1.1) from the newly discovered thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 (SspCA) was investigated for its inhibition with a large series of sulfonamides and a sulfamate, the classical inhibitors of these zinc enzymes. SspCA showed an inhibition profile with these compounds very similar to that of the predominant human cytosolic isoform hCA II, and not to that of the bacterial α-CA from Helicobacter pylori. Some clinically used drugs such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, celecoxib and sulthiame were low nanomolar SspCA/hCA II inhibitors (KIs in the range of 4.5-12.3nM) whereas simple aromatic/heterocyclic sulfonamides were less effective, micromolar inhibitors. As this highly catalytically active and thermostable enzyme may show biotechnological applications, its inhibition studies may be relevant for designing on/off systems to control its activity. PMID:22883029

  18. Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats

    Institute of Scientific and Technical Information of China (English)

    Hai-ju ZHANG; Ruo-peng SUN; Ge-fei LEI; Lu YANG; Chun-xi LIU

    2008-01-01

    Objective: To examine modulations caused by cyclooxygenase-2 (COX-2) inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms. Methods:Celecoxib (a COX-2 inhibitor) was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mIPSCs (miniature GABAergic inhibitory postsynaptic currents) of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis wore analyzed by immunohistochemistry, and expressions of α-subunit of γ-amino butyric acid (GABAA) receptors and mitogen-activated protein kinase/extracellular sig-nal-regulated protein kinase (MAPK/ERK) activity were detected by Western blotting. Results: Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABAA receptors. NS-398 (N-2-cyclohexyloxy-4-nitrophenyl-methanesuifonamide), another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs. Conclusion: The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.

  19. The Effect of Celecoxib, a Cyclooxygenase-2 Inhibitor on Noise- Induced Hearing Loss

    OpenAIRE

    Akram Pourbakht

    2013-01-01

    Objective(s): Noise-induced hearing loss (NIHL) is the major cause of acquired hearing loss.  Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, is a non- steroidal anti- inflammatory drug (NSAID) with known antioxidant and antineoplastic activity. Therefore, we monitored the extent of temporary noise- induced threshold shifts (TTS) and cochlear damage caused by high level 4- kHz noise exposure to verify the differences with those pretreated with celecoxib. Materials and Methods: Ten male albin...

  20. Helicobacter pylori inhibits dendritic cell maturation via interleukin-10-mediated activation of the signal transducer and activator of transcription 3 pathway.

    Science.gov (United States)

    Rizzuti, David; Ang, Michelle; Sokollik, Christiane; Wu, Ted; Abdullah, Majd; Greenfield, Laura; Fattouh, Ramzi; Reardon, Colin; Tang, Michael; Diao, Jun; Schindler, Christian; Cattral, Mark; Jones, Nicola L

    2015-01-01

    Helicobacter pylori infects the human gastric mucosa causing a chronic infection that is the primary risk factor for gastric cancer development. Recent studies demonstrate that H. pylori promotes tolerogenic dendritic cell (DC) development indicating that this bacterium evades the host immune response. However, the signaling pathways involved in modulating DC activation during infection remain unclear. Here, we report that H. pylori infection activated the signal transducer and activator of transcription 3 (STAT3) pathway in murine bone marrow-derived DCs (BMDCs) and splenic DCs isolated ex vivo. Isogenic cagA-, cagE-, vacA- and urease-mutants exhibited levels of phosphoSTAT3 that were comparable to in the wild-type (WT) parent strain. H. pylori-infected BMDCs produced increased immunosuppressive IL-10, which activated STAT3 in an autocrine/paracrine fashion. Neutralization of IL-10 prevented H. pylori-mediated STAT3 activation in both BMDCs and splenic DCs. In addition, anti-IL-10 treatment of infected H. pylori-BMDCs was associated with increased CD86 and MHC II expression and enhanced proinflammatory IL-1β cytokine secretion. Finally, increased CD86 and MHC II expression was detected in H. pylori-infected STAT3 knockout DCs when compared to WT controls. Together, these results demonstrate that H. pylori infection induces IL-10 secretion in DCs, which activates STAT3, thereby modulating DC maturation and reducing IL-1β secretion. These findings identify a host molecular mechanism by which H. pylori can manipulate the innate immune response to potentially favor chronic infection and promote carcinogenesis. PMID:25412627

  1. The Effect of Celecoxib, a Cyclooxygenase-2 Inhibitor on Noise- Induced Hearing Loss

    Directory of Open Access Journals (Sweden)

    Akram Pourbakht

    2013-05-01

    Full Text Available Objective(s: Noise-induced hearing loss (NIHL is the major cause of acquired hearing loss.  Celecoxib, a cyclooxygenase-2 (COX-2 inhibitor, is a non- steroidal anti- inflammatory drug (NSAID with known antioxidant and antineoplastic activity. Therefore, we monitored the extent of temporary noise- induced threshold shifts (TTS and cochlear damage caused by high level 4- kHz noise exposure to verify the differences with those pretreated with celecoxib. Materials and Methods: Ten male albino guinea pigs (300-350 g in weight were randomly allocated into two groups: the primal group was exposed to 4- kHz octave band noise at 102 dB SPL for 3 hrs (group 1, n=5;  the latter pretreated with 50 mg/ kg celecoxib for 3 days, then  exposed to noise (group 2, n=5.  Before exposure and one hr after noise exposure, threshold shifts were evaluated with auditory brainstem responses (ABR and finally the animals were euthanized for histological evaluation.  Results: Comparing the threshold shifts before/after noise exposure with those pretreated, we found out that TTS caused by noise exposure did not show significant mitigation by celecoxib.  By observing the organ of Corti at lower middle turn of cochlea in celecoxib pretreated group, considerable hair cell loss was discovered. Conclusion:The current study clearly confirmed that celecoxib had no attenuation against temporary noise-induced hearing loss.

  2. Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion

    Directory of Open Access Journals (Sweden)

    Ali Javed

    2008-07-01

    Full Text Available Abstract Background Celecoxib, a selective cyclo-oxygenase-2 inhibitor has been recommended orally for the treatment of arthritis and osteoarthritis. Long term oral administration of celecoxib produces serious gastrointestinal side effects. It is a highly lipophilic, poorly soluble drug with oral bioavailability of around 40% (Capsule. Therefore the aim of the present investigation was to assess the skin permeation mechanism and bioavailability of celecoxib by transdermally applied nanoemulsion formulation. Optimized oil-in-water nanoemulsion of celecoxib was prepared by the aqueous phase titration method. Skin permeation mechanism of celecoxib from nanoemulsion was evaluated by FTIR spectral analysis, DSC thermogram, activation energy measurement and histopathological examination. The optimized nanoemulsion was subjected to pharmacokinetic (bioavailability studies on Wistar male rats. Results FTIR spectra and DSC thermogram of skin treated with nanoemulsion indicated that permeation occurred due to the disruption of lipid bilayers by nanoemulsion. The significant decrease in activation energy (2.373 kcal/mol for celecoxib permeation across rat skin indicated that the stratum corneum lipid bilayers were significantly disrupted (p Conclusion Results of skin permeation mechanism and pharmacokinetic studies indicated that the nanoemulsions can be successfully used as potential vehicles for enhancement of skin permeation and bioavailability of poorly soluble drugs.

  3. Celecoxib coupled to dextran via a glutamic acid linker yields a polymeric prodrug suitable for colonic delivery

    Directory of Open Access Journals (Sweden)

    Lee Y

    2015-07-01

    Full Text Available Yonghyun Lee,1,2,* Jungyun Kim,1,* Wooseong Kim,1,* Joon Nam,1,* Seongkeun Jeong,1 Sunyoung Lee,1 Jin-Wook Yoo,1 Min-Soo Kim,1 Yunjin Jung1 1College of Pharmacy, Pusan National University, Busan, 2Bio-Nanomedicine Laboratory, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea *These authors contributed equally to this work Abstract: Celecoxib, a selective cyclooxygenase-2 inhibitor, is potentially useful for the treatment of colonic diseases such as colorectal cancer and colitis. However, the cardiovascular toxicity of celecoxib limits its routine use in the clinic. Generally, colon-specific delivery of a drug both increases the therapeutic availability in the large intestine and decreases the systemic absorption of the drug, most likely resulting in enhanced therapeutic effects against colonic diseases such as colitis and reduced systemic side effects. To develop a colon-specific prodrug of celecoxib that could reduce its cardiovascular toxicity and improve its therapeutic activity, dextran–glutamic acid–celecoxib conjugate (glutam-1-yl celecoxib-dextran ester [G1CD] was prepared and evaluated. While stable in pH 1.2 and 6.8 buffer solutions and small-intestinal contents, G1CD efficiently released celecoxib in cecal contents. Oral administration of G1CD to rats delivered a larger amount of celecoxib to the large intestine than free celecoxib. G1CD prevented the systemic absorption of celecoxib and did not decrease the serum level of 6-ketoprostaglandin F1α, an inverse indicator of cardiovascular toxicity of celecoxib. Collectively, G1CD may be a polymeric colon-specific celecoxib prodrug with therapeutic and toxicological advantages. Keywords: colon-specific drug delivery, dextran, celecoxib, prodrug, cardiovascular toxicity

  4. Formulation, characterization, and in vivo evaluation of celecoxib-PVP solid dispersion nanoparticles using supercritical antisolvent process.

    Science.gov (United States)

    Ha, Eun-Sol; Choo, Gwang-Ho; Baek, In-Hwan; Kim, Min-Soo

    2014-12-04

    The aim of this study was to develop celecoxib-polyvinylpyrrolidone (PVP) solid dispersion nanoparticles with and without surfactant using the supercritical antisolvent (SAS) process. The effect of different surfactants such as gelucire 44/14, poloxamer 188, poloxamer 407, Ryoto sugar ester L1695, and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on nanoparticle formation and dissolution as well as oral absorption of celecoxib-PVP K30 solid dispersion nanoparticles was investigated. Spherical celecoxib solid dispersion nanoparticles less than 300 nm in size were successfully developed using the SAS process. Analysis by differential scanning calorimetry and powder X-ray diffraction showed that celecoxib existed in the amorphous form within the solid dispersion nanoparticles fabricated using the SAS process. The celecoxib-PVP-TPGS solid dispersion nanoparticles significantly enhanced in vitro dissolution and oral absorption of celecoxib relative to that of the unprocessed form. The area under the concentration-time curve (AUC0→24 h) and peak plasma concentration (Cmax) increased 4.6 and 5.7 times, respectively, with the celecoxib-PVP-TPGS formulation. In addition, in vitro dissolution efficiency was well correlated with in vivo pharmacokinetic parameters. The present study demonstrated that formulation of celecoxib-PVP-TPGS solid dispersion nanoparticles using the SAS process is a highly effective strategy for enhancing the bioavailability of poorly water-soluble celecoxib.

  5. Formulation, Characterization, and in Vivo Evaluation of Celecoxib-PVP Solid Dispersion Nanoparticles Using Supercritical Antisolvent Process

    Directory of Open Access Journals (Sweden)

    Eun-Sol Ha

    2014-12-01

    Full Text Available The aim of this study was to develop celecoxib-polyvinylpyrrolidone (PVP solid dispersion nanoparticles with and without surfactant using the supercritical antisolvent (SAS process. The effect of different surfactants such as gelucire 44/14, poloxamer 188, poloxamer 407, Ryoto sugar ester L1695, and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS on nanoparticle formation and dissolution as well as oral absorption of celecoxib-PVP K30 solid dispersion nanoparticles was investigated. Spherical celecoxib solid dispersion nanoparticles less than 300 nm in size were successfully developed using the SAS process. Analysis by differential scanning calorimetry and powder X-ray diffraction showed that celecoxib existed in the amorphous form within the solid dispersion nanoparticles fabricated using the SAS process. The celecoxib-PVP-TPGS solid dispersion nanoparticles significantly enhanced in vitro dissolution and oral absorption of celecoxib relative to that of the unprocessed form. The area under the concentration-time curve (AUC0→24 h and peak plasma concentration (Cmax increased 4.6 and 5.7 times, respectively, with the celecoxib-PVP-TPGS formulation. In addition, in vitro dissolution efficiency was well correlated with in vivo pharmacokinetic parameters. The present study demonstrated that formulation of celecoxib-PVP-TPGS solid dispersion nanoparticles using the SAS process is a highly effective strategy for enhancing the bioavailability of poorly water-soluble celecoxib.

  6. Inflammation, immunity, and vaccines for Helicobacter pylori

    DEFF Research Database (Denmark)

    D'Elios, Mario M; Andersen, Leif P

    2009-01-01

    Helicobacter pylori infects almost half of the population worldwide and represents the major cause of gastroduodenal diseases, such as duodenal and gastric ulcer, gastric adenocarcinoma, autoimmune gastritis, and B-cell lymphoma of mucosa-associated lymphoid tissue. Helicobacter pylori induces...... the activation of a complex and fascinating cytokine and chemokine network in the gastric mucosa. Different bacterial and environmental factors, other concomitant infections, and host genetics may influence the balance between mucosal tolerance and inflammation in the course of H. pylori infection. An inverse...... association between H. pylori prevalence and the frequencies of asthma and allergies was demonstrated, and the neutrophil activating protein of H. pylori was shown to inhibit the allergic inflammation of bronchial asthma. During the last year, significant progress was made on the road to the first efficient...

  7. Release of celecoxib from a bi-layer biomimetic tendon sheath to prevent tissue adhesion.

    Science.gov (United States)

    Li, Laifeng; Zheng, Xianyou; Fan, Dapeng; Yu, Shiyang; Wu, Di; Fan, Cunyi; Cui, Wenguo; Ruan, Hongjiang

    2016-04-01

    Posttraumatic tendon adhesion limits the motion of the limbs greatly. Biomimetic tendon sheaths have been developed to promote tendon healing and gliding. However, after introduction of these biomaterials, the associated inflammatory responses can decrease the anti-adhesion effect. Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) that can decrease inflammation responses. We blended hyaluronic acid and poly(l-lactic acid)-polyethylene glycol (PELA) with microgel electrospinning technology to form an inner layer of a bi-layer biomimetic sheath using sequential electrospinning of an outer celecoxib-PELA layer. Electrospun bi-layer fibrous membranes were mechanically tested and characterized by morphology, surface wettability, and drug release. The tensile strength showed a decreased trend and water contact angles were 114.7 ± 3.9°, 103.6 ± 4.4°, 116.3 ± 5.1°, 122.8 ± 4.7°, and 126.5 ± 4.2° for the surface of PELA, hyaluronic acid-PELA, 2, 6, and 10% celecoxib-PELA electrospun fibrous membranes, respectively. In vitro drug release studies confirmed burst release and then sustained release from the fibrous membranes containing celecoxib for 20 days. In a chicken model of flexor digitorum profundus tendon surgery, the outer celecoxib/PELA layer offered advanced anti-adhesion roles compared to the outer PELA layer and the inner hyaluronic acid-loaded PELA layer still offered tendon healing and gliding. Thus, celecoxib-loaded anti-adhesive tendon sheaths can continuously offer bi-layer biomimetic tendon sheath effects with celecoxib release from the outer layer to prevent tendon adhesion. PMID:26838844

  8. The Chemopreventive Effect of Tamoxifen Combined with Celecoxib on DMBA chemically-Induced Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoxu Liu; Huafeng Kang; Xijing Wang; Zhijun Dai; Fengjie Xue; Xinghuan Xue

    2007-01-01

    Objective: To investigate the chemopreventive effect of tamoxifen combined with a COX-2 selective inhibitor, celecoxib, on breast cancer in rats chemically induced by 7,12-dimethylben (a)anthracene (DMBA). Methods:DMBA was irrigated into the stomaches of SD female rats to build breast cancer model. A total of 120 rats were divided into four groups: control group, tamoxifen group, celecoxib group and combined group. The incidence rate, latent period, number and volume of breast cancer were detected and analyzed. Results:The tumor incidence rate of tamoxifen group (48.15%, 13/27) and celecoxib group (50.00%,14/28) were lower than that of control group (85.71%, 24/28), but higher than that of combined group (21.43%, 6/28). The tumor's latent period of tamoxifen group (97.54±1.85 d) and celecoxib group (96.79±2.89 d) were longer than that of control group (89.50±5.99 d), but shorter than that of combined group (103.67±3.39 d). The average tumor number of tamoxifen group (1.77±0.73) and celecoxib group (1.71±0.61) were less than that of control group (3.50±1.62), but more than that of combined group ( 1.17±0.42 ). The average tumor volume of tamoxifen group (1.78±0.71 cm3) and celecoxib group (2.05±1.04 cm3) were smaller than that of control group (6.42±3.96 cm3), but bigger than that of combined group (0.71±0.96 cm3) (P < 0.05 respectively).Conclusion:Celecoxib and tamoxifen are effective drugs in preventing the occurrence of rat breast cancer chemically induced by DMBA. Furthermore, combination of them has better chemopreventive effect.

  9. Celecoxib-related gastroduodenal ulcer and cardiovascular events in a randomized trial for gastric cancer prevention

    Institute of Scientific and Technical Information of China (English)

    Guo-Shuang Feng; Harry HX Xia; Ji-You Li; Shiu Kum Lam; Wei-Cheng You; Jun-Ling Ma; Benjamin CY Wong; Lian Zhang; Wei-Dong Liu; Kai-Feng Pan; Lin Shen; Xiao-Dong Zhang; Jie Li

    2008-01-01

    AIM: To evaluate the long-term risk of gastroduodenal ulcer and cardiovascular events induced by celecoxib in a population-based, randomized, double-blind,placebo-controlled study.METHODS: From 2004 to 2006, a total of 1024 Chinese patients (aged 35 to 64 years) with severe chronic atrophic gastritis, intestinal metaplasia or dysplasia were randomly assigned to receive 200 mg of celecoxib twice daily or placebo in Linqu County (Shandong Province, China), a high-risk area of gastric cancer. All gastroduodenal ulcer and cardiovascular events occurred were recorded and the patients were followed up for 1.5 years after treatment. At the end of the trial, a systematic interview survey about other adverse events was conducted.RESULTS: Gastroduodenal ulcer was detected in 19 of 463 (3.72%) patients who Received: celecoxib and 17 of 473 (3.31%) patients who Received placebo,respectively (odds ratio = 1.13, 95% CI = 0.58-2.19).Cardiovascular (CV) events occurred in 4 patients who received celecoxib and in 5 patients who received placebo,respectively.Compared with those who received placebo,patients who received celecoxib had no significant increase in occurrence of Cvevents (hazard ratio = 0.84,95% CI =0.23-3.15).Among the adverse events acquired by interview survey,only the frequency of bloating was significantly higher in patients treated with celecoxib than in those treated with placebo.CONCLUSION:Treatment of gastric cancer with celecoxib is not associated with increased risk of gastroduodenal ulcer and cardiovascular events.

  10. Treatment of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Adam Harris

    2001-01-01

    @@ INTRODUCTION Using an evidence-based approach this review discusses the current treatment of Helicobacter pylori infection in patients with peptic ulcer disease, functional (non-ulcer)dyspepsia or gastro-oesophageal reflux disease (GORD).It also briefly addresses the potential role of eradication of H . pylori in preventing gastric cancer .

  11. Activation of Helicobacter pylori causes either autoimmune thyroid diseases or carcinogenesis in the digestive tract.

    Science.gov (United States)

    Astl, J; Šterzl, I

    2015-01-01

    Helicobacter pylori has been implicated in stimulation of immune system, development of autoimmune endocrinopathies as autoimmune thyroiditis (AT) and on other hand induction of immunosupresion activates gastric and extra-gastric diseases such as gastric ulcer or cancer. It causes persistent lifelong infection despite local and systemic immune response. Our results indicate that Helicobacter pylori might cause inhibition of the specific cellular immune response in Helicobacter pylori-infected patients with or without autoimmune diseases such as AT. We cannot also declare the carcinogenic effect in oropharynx. However the association of any infection agents and cancerogenesis exists. The adherence of Helicobacter pylori expression and enlargement of benign lymphatic tissue and the high incidence of the DNA of Helicobacter pylori in laryngopharyngeal and oropharyngeal cancer is reality. LTT appears to be a good tool for detection of immune memory cellular response in patients with Helicobacter pylori infection and AT. All these complications of Helicobacter pylori infection can be abrogated by successful eradication of Helicobacter pylori.

  12. Infecciones por helicobacter pylori Helicobacter pylori infections

    Directory of Open Access Journals (Sweden)

    Liliam Alvarez Gil

    1994-02-01

    Full Text Available

    Se revisan los conocimientos sobre el papel de Helicobacter pylori en varias enfermedades gastroduodenales como la gastritis crónica (GC, úlcera gástrica (UG, úlcera duodenal (UD y dispepsia no ulcerosa (DNU. La revisión abarca aspectos históricos, microbiológicos, clínicos, epidemiológicos, diagnósticos de laboratorio, terapéuticos y de patogénesis.

    The current knowledge of the role of Helicobacter Pylori in several gastroduodenal  diseases is reviewed. It includes chronic gastritis, gastric and duodenal ulcers and nonulcerous dyspepsia. The following aspects are treated in this paper: history, microbiology. Clinical presentation, epidemiology, laboratory diagnosis, therapy and pathogenesis.

  13. Enterohepatic Helicobacter other than Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Beatriz Mateos Muñoz

    2013-09-01

    Full Text Available The Helicobacter genus includes Gram negative bacteria which were originally considered to belong to the Campylobacter genus. They have been classified in a separate genus since 1989 because they have different biochemical characteristics, with more than 24 species having been identified and more still being studied. H. pylori is the best known. It has an important etiopathogenic role in peptic ulcer disease and gastric cancer. Enterohepatic Helicobacter s (EHH other than H. pylori colonize the bowel, biliary tree and liver of animals and human beings with pathogenic potential. The difficulties existing to correctly isolate these microorganisms limit the description of their true prevalence and of the diseases they cause. Many studies have tried to discover the different clinical implications of EHH. Diseases like chronic liver disease, autoimmune hepatitis, hepatocarcinoma, autoimmune hepatobiliary disease, biliary lithiasis, cholangiocarcinoma and gallbladder cancer, Meckel's diverticulum, acute appendicitis and inflammatory bowel disease have been related with different EHH species with different results, although their prevalence is greater than in healthy subjects. However, these data are currently not sufficient to draw definitive conclusions. Finally, the best known role of EHH in bowel disease is production of acute and chronic diarrhea pictures initially referred to as Campylobacter. H. pullorum has been identified in patients with acute gastroenteritis. The correct identification of EHH as producers of infectious gastroenteritis is found in its antibiotic susceptibility. It is generally macrolide-susceptible and quinolone-resistant.

  14. Perioperative celecoxib administration for pain management after total knee arthroplasty – A randomized, controlled study

    Directory of Open Access Journals (Sweden)

    Lin Wei-Peng

    2008-06-01

    Full Text Available Abstract Background Non-steroidal anti-inflammatory drugs (NSAIDs are recommended for multimodal postoperative pain management. We evaluated opioid-sparing effects and rehabilitative results after perioperative celecoxib administration for total knee arthroplasty. Methods This was a prospective, randomized, observer-blind control study. Eighty patients that underwent total knee arthroplasty were randomized into two groups of 40 each. The study group received a single 400 mg dose of celecoxib, one hour before surgery, and 200 mg of celecoxib every 12 hours for five days, along with patient-controlled analgesic (PCA morphine. The control group received only PCA morphine for postoperative pain management. Visual analog scale (VAS pain scores, active range of motion (ROM, total opioid use and postoperative nausea/vomiting were analyzed. Results Groups were comparable for age, pre-operative ROM, operation duration and intraoperative blood loss. Resting VAS pain scores improved significantly in the celecoxib group, compared with controls, at 48 hrs (2.13 ± 1.68 vs. 3.43 ± 1.50, p = 0.03 and 72 hrs (1.78 ± 1.66 vs. 3.17 ± 2.01, p = 0.02 after surgery. Active ROM also increased significantly in the patients that received celecoxib, especially in the first 72 hrs [40.8° ± 17.3° vs. 25.8° ± 11.5°, p = 0.01 (day 1; 60.7° ± 18.1° vs. 45.0° ± 17.3°, p = 0.004 (day 2; 77.7° ± 15.1° vs. 64.3° ± 16.9°, p = 0.004 (day 3]. Opioid requirements decreased about 40% (p = 0.03 in the celecoxib group. Although patients suffering from post-operative nausea/vomiting decreased from 43% in control group to 28% in celecoxib group, this was not significant (p = 0.57. There were no differences in blood loss (intra- and postoperative between the groups. Celecoxib resulted in no significant increase in the need for blood transfusions. Conclusion Perioperative celecoxib significantly improved postoperative resting pain scores at 48 and 72 hrs, opioid

  15. Effect of polyvinylpyrrolidone on complexation and dissolution rate of β- and hydroxypropyl-β-cyclodextrin complexes of celecoxib

    Directory of Open Access Journals (Sweden)

    Chowdary KPR

    2006-01-01

    Full Text Available Complexation of celecoxib with β-cyclodextrin and hydroxypropyl-β-cyclodextrin in the presence and absence of polyvinylpyrrolidone and the effect of polyvinylpyrrolidone on the solubilizing efficiency of cyclodextrins and on the dissolution rate of celecoxib from the cyclodextrin complexes were investigated. The phase solubility studies indicated the formation of celecoxib-β-cyclodextrin and celecoxib-hydroxypropyl-β-cyclodextrin inclusion complexes at a 1:1 M ratio in solution, both in the presence and absence of polyvinylpyrrolidone. The complexes formed were quite stable. The solubility and dissolution rate of celecoxib were markedly enhanced by complexation with β-cyclodextrin and hydroxypropyl-β-cyclodextrin. Celecoxib-hydroxypropyl-β-cyclodextrin (1:2 inclusion complex gave a 36.57-fold increase in the dissolution rate of celecoxib. Addition of polyvinylpyrrolidone resulted in higher complexation efficiency and markedly enhanced solubilizing efficiency of β-cyclodextrin and hydroxypropyl-β-cyclodextrin. Solid inclusion complexes of cyclodextrins with polyvinylpyrrolidone gave several times higher rates of dissolution than those of celecoxib and its complexes with cyclodextrins alone.

  16. Effect of Premedication With Celecoxib and Gelofen on Reduction of Post-Endodontic Pain

    Directory of Open Access Journals (Sweden)

    Mirzaie M

    2011-12-01

    Full Text Available Background and Aims: Non-steroidal anti-inflammatory drugs (NSAIDs are the most common drugs prescribed for controlling and post root canal treatment pain. During the last decade, a new generation of NSAIDs has been introduced such as Celecoxib and Gelofen with less gastrointestinal side effects and more analgesic effect. No studies have been performed to compare Celecoxib and Gelofen with other NSAIDs considering the reduction of post-endodontic pain; therefore, this study was designed.Materials and Methods: In this randomized double blind clinical trial study, 90 patients were divided into 3 groups and underwent root canal therapy. Celecoxib, Gelofen, or placebo was randomized prescribed to the patients 1 hour before treatment. The intensity of pain was recorded using visual analog scale (VAS at 4, 8, 12, 24, 48 hours after completion of root canal treatment. The data were analyzed by means of repeated measurements, multiple comparisons and one-way ANOVA tests using SPSS software. P<0.05 was considered as the level of significance.Results: The results showed significant difference between Celecoxib and Gelofen in comparison with placebo at 8 and 12 hours after initiation of treatment. There was no significant difference among three groups at 4, 24, and 48 hours after initiation of treatment. Conclusion: According to the results, use of Gelofen or Celecoxib before treatment reduces post-endodontic pain. These drugs can be prescribed before initiation of treatment as the effective agents for reduction of post-endodontic pain

  17. Utilization of thin film method for preparation of celecoxib loaded liposomes

    Directory of Open Access Journals (Sweden)

    Eskandar Moghimipour

    2012-06-01

    Full Text Available Purpose: Celecoxib is nonsteroiddal anti-inflammatory drug that has been used extensively to treat patients with arthritis. The aim of the present study was to formulate and characterize liposomal vesicles loaded with celecoxib. Methods: Liposomes were prepared by thin film method using soya lecithin and cholesterol. The release of drug was determined using a dialysis membrane method. Liposomes were characterized by Differential Scanning Calorimetery (DSC, Transmission Electron Microscopy (TEM and their particle size was also determined. Results: The results showed that the drug encapsulation efficiency was 67.34% and there was 67.16% release after 0.5, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h. Results of particle size determination showed a mean size of 677nm and nanoparticles were spherical as shown by TEM. The DSC curve of lecithin, cholesterol and celecoxib were different from celecoxib containing liposome. Conclusion: The results of characterization of the vesicles indicated the potential application of celecoxib loaded liposome as carrier system.

  18. Celecoxib enhances the detoxification of diethylnitrosamine in rat liver cancer

    Institute of Scientific and Technical Information of China (English)

    Martha Estela Salcido-Neyoy; Adolfo Sierra-Santoyo; Olga Beltrán-Ramírez; José Roberto Macías-Pérez; Saúl Villa-Trevi(n)o

    2009-01-01

    AIM: To study the effect of celecoxib (CXB) on diethylnitrosamine activation through the regulation of cytochrome P450 in a hepatocarcinogenesis model. METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into five groups, a nontreated group (NT), a diethylnitrosamine-treated group (DEN), a DEN+CXB-treated group (DEN+CXB), and CXB 8 d-treated and CXB 32 d-treated groups. The effects of celecoxib on the enzymatic activities of CYP1A1, 2A, 2B1/2, and 2E1 were assessed in hepatic microsomes 24 h after DEN administration.Changes in CYP1A1 and CYP2B1/2 protein expression were also evaluated. The rate of DEN metabolism was measured by the production of the deethylation metabolite acetaldehyde, and the denitrosation metabolite nitrite.RESULTS: DEN+CXB administration produced a significant increase in the enzymatic activities of CYP2B1/2 and 1A1, whereas it did not change the activities of CYP2A and 2E1, compared to that of the DEN group. CXB treatment for eight days did not produce a significant effect on enzymatic activity when compared to the NT group; however, when it was administered for prolonged times (CXB 32 d group), the enzymatic activities were increased in a similar pattern to those in the DEN+CXB group. The observed increase in the enzymatic activities in the DEN+CXB group was accompanied by an increase in the CYP2B1/2 protein levels; no changes were observed in the levels of CYP1A1. In vitro, CXB increased the denitrosation of DEN, a pathway of metabolic detoxification. The addition of SKF-525A, a preferential inhibitor of CYP2B, abrogated the denitrosation of DEN. CONCLUSION: These results suggest that the mechanism of action of CXB involves enhancement of the detoxification of DEN by an increasing denitrosation via CYP2B1/2.

  19. Novel combination of sorafenib and celecoxib provides synergistic anti-proliferative and pro-apoptotic effects in human liver cancer cells.

    Directory of Open Access Journals (Sweden)

    Melchiorre Cervello

    Full Text Available Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC. Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex® is a selective cyclooxygenase-2 (COX-2 inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of the combination, we investigated the expression profile of the combination-treated liver cancer cell lines using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell-cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell lines displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semi-quantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomic analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies.

  20. Cyclooxgenase-2 inhibiting perfluoropoly (ethylene glycol ether theranostic nanoemulsions-in vitro study.

    Directory of Open Access Journals (Sweden)

    Sravan Kumar Patel

    Full Text Available Cylcooxgenase-2 (COX-2 expressing macrophages, constituting a major portion of tumor mass, are involved in several pro-tumorigenic mechanisms. In addition, macrophages are actively recruited by the tumor and represent a viable target for anticancer therapy. COX-2 specific inhibitor, celecoxib, apart from its anticancer properties was shown to switch macrophage phenotype from tumor promoting to tumor suppressing. Celecoxib has low aqueous solubility, which may limit its tumor inhibiting effect. As opposed to oral administration, we propose that maximum anticancer effect may be achieved by nanoemulsion mediated intravenous delivery. Here we report multifunctional celecoxib nanoemulsions that can be imaged by both near-infrared fluorescence (NIRF and (19F magnetic resonance. Celecoxib loaded nanoemulsions showed a dose dependent uptake in mouse macrophages as measured by (19F NMR and NIRF signal intensities of labeled cells. Dramatic inhibition of intracellular COX-2 enzyme was observed in activated macrophages upon nanoemulsion uptake. COX-2 enzyme inhibition was statistically equivalent between free drug and drug loaded nanoemulsion. However, nanoemulsion mediated drug delivery may be advantageous, helping to avoid systemic exposure to celecoxib and related side effects. Dual molecular imaging signatures of the presented nanoemulsions allow for future in vivo monitoring of the labeled macrophages and may help in examining the role of macrophage COX-2 inhibition in inflammation-cancer interactions. These features strongly support the future use of the presented nanoemulsions as anti-COX-2 theranostic nanomedicine with possible anticancer applications.

  1. Eficácia e tolerabilidade da nimesulida versus celecoxib na osteoartrite Efficacy and tolerability of nimesulide versus celecoxib in osteoarthritis

    Directory of Open Access Journals (Sweden)

    Nilzio Antonio da Silva

    2001-03-01

    Full Text Available O objetivo do estudo foi comparar a eficácia e a tolerabilidade da nimesulida versus o celecoxib no tratamento da osteoartrite. A casuística envolveu 57 pacientes com idade entre 40 e 80 anos, que foram randomizados em dois grupos, recebendo as medicações do estudo durante 30 dias de forma simples-cega na dosagem de um comprimido de 100mg de nimesulida duas vezes ao dia e uma cápsula de 100mg de celecoxib duas vezes ao dia. Após a inclusão no estudo na visita basal, foram realizadas três visitas com intervalo de dez dias entre elas. Os aspectos analisados foram: dor em repouso, dor em movimento e dor noturna, através de uma escala analógica da dor, duração da rigidez matinal, capacidade funcional (HAQ, classe funcional ACR-1991 e o índice de gravidade para osteoartrite de joelhos em todas as visitas. Foi também avaliado o tempo para andar 15 metros naqueles pacientes com acometimento de joelhos ou quadril. A avaliação da eficácia e tolerabilidade foi realizada pelo investigador e pelo paciente nas três visitas após o início do tratamento. Os eventos adversos foram registrados durante todo o período do estudo. Houve diminuição significativa e semelhante nas médias da escala para dor ao movimento e dor em repouso para ambos medicamentos em todas as visitas. Houve diminuição da dor noturna ao longo do tratamento no grupo celecoxib e a partir da visita 3 no grupo nimesulida, e ao final do estudo, as médias dos dois grupos foram semelhantes ( p = 0,152. As médias da duração da rigidez matinal diminuíram significativamente no grupo tratado com nimesulida durante todo o seguimento, e no grupo celecoxib a partir da visita 3, sendo semelhantes ao final do estudo ( p= 0,993. O tempo médio para andar 15 metros diminuiu significativamente no grupo nimesulida na visita 4 (p The aim of the present study was to compare the efficacy and tolerability of nimesulide versus celecoxib in the treatment of osteoarthritis. Fifty seven

  2. Rapid and sensitive spectrofluorimetric method for the estimation of celecoxib and flurbiprofen

    Directory of Open Access Journals (Sweden)

    Chandran S

    2006-01-01

    Full Text Available In this study new, rapid and sensitive spectrofluorimetric methods for the quantitative estimation of celecoxib and flurbiprofen in pure form and in their pharmaceutical dosage forms were developed. The solvent systems, wavelengths of detection (excitation and emission were optimized in order to maximize the sensitivity and minimize the cost of analysis for both the drugs. No extraction procedure was employed for analysis of these compounds in their formulation matrix, which reduced the time of sample preparation. The excitation and emission wavelengths were found to be 256 nm and 403 nm respectively for celecoxib in water and 250 nm and 314 nm respectively for flurbiprofen in 1:1 mixture of methanol and 0.1N sulphuric acid. The linear regression equations obtained by least square regression method for fluorescence intensity (FI and concentration in ng/ml (conc were FI=1.2874´conc+22.647, for celecoxib; and FI=27.7970´conc+46.049, for flurbiprofen. The limit of detection as per the error propagation theory was found to be 4.97 ng/ml and 0.99 ng/ml for celecoxib and flurbiprofen respectively. The developed methods were successfully employed with high degree of precision and accuracy for the estimation of total drug content in two commercial capsule formulations of celecoxib and two ophthalmic drops of flurbiprofen. The results of analysis were treated statistically, as per International Conference on Harmonization guidelines for validation of analytical procedures, and by recovery studies. It was concluded that developed methods are simple, accurate, sensitive, precise and reproducible and could be applied directly and easily to the pharmaceutical preparations of celecoxib and flurbiprofen.

  3. Transmission of Helicobacter pylori

    OpenAIRE

    Axon, Anthony T. R.

    1999-01-01

    Helicobacter gastroduodenitis is a serious chronic infectious disease that is responsible for widespread morbidity and mortality. An understanding of the way in which it spreads is fundamentally important when considering measures for its control. Its prevalence is highest in the developing world and in individuals with a disadvantaged socio-economic childhood. The disease is believed to be contracted during the early years of life. A faeco-oral mode of transmission is considered by many to b...

  4. Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Yvan Vandenplas

    2000-01-01

    @@ IS THERE ANYTHING NEW? Helicobacter pylori has been for many years a forgotten bacterium, since the first report on this spiral organism dated from the 19th century[1]. As early as in 1906, an association between a spiral organism and gastric carcinoma was suggested[2].Doenges reported in 1938 that on autopsy not less than 40% of human stomachs were found to be invaded by spiral organisms[3].

  5. Helicobacter pylori Pathogenic Factors

    OpenAIRE

    Salamina, M

    2014-01-01

    From 1994, Helicobacter pylori was classified by WHO (World Health Organization) as a class I carcinogen and its infection has been associated to gastroduodenal disease. It colonizes more than half of worldwide population, with a prevalent infection rate in developed countries. In spite of the majority of infected people are asymptomatic, around 20% develop severe pathologies like peptic ulcers and the 1% lymphoma of the mucosa-associated lymphoid tissue (MALT) and stomach cancer. This signif...

  6. Celecoxib plays a multiple role to peripheral blood lymphocytes and allografts in acute rejection in rats after cardiac transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xue-feng; ZHANG Fan; LIU Hong-yu; SUN Guo-dong; LIU Zong-hong; L(U) Hang; CHI Chao; LI Chun-yu

    2009-01-01

    Background Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug used as an adjuvant to sensitize cancer cells to apoptosis. However, in rats suffering from acute rejection, celecoxib reduced apoptosis of myocardial cells. We hypothesize that celecoxib reduces myocardial apoptosis either by inducing apoptosis in peripheral blood lymphocytes (PBLs) or by altering the percentage of CD4+ and CD8+ lymphocytes. Methods After cardiac transplantation, rats were administered intragastrically with celecoxib (50 mg/kg per day) for 3, 5 or 7 days, at which time the graft was excised and evaluated for organ rejection. In addition, PBLs were isolated from the blood to determine PBLs apoptosis, and the percentage of CD4+ and CD8+ lymphocytes. Results Celecoxib induced PBLs apoptosis in 3 days, but protected the cells from apoptosis at 5 and 7 days. Also, the percentage of CD4+ lymphocytes decreased only at 3 days, but a reduction in the percentage of CD8+ lymphocytes was not seen until 7 days after the transplant surgery. Celecoxib only decreased acute rejection at 5 days, with no discernible difference in rejection after 3 and 7 days. Conclusions The results suggested that celecoxib displayed a multiple physiological function in a time-dependent manner.

  7. Urease from Helicobacter pylori is inactivated by sulforaphane and other isothiocyanates.

    Science.gov (United States)

    Fahey, Jed W; Stephenson, Katherine K; Wade, Kristina L; Talalay, Paul

    2013-05-24

    Infections by Helicobacter pylori are very common, causing gastroduodenal inflammation including peptic ulcers, and increasing the risk of gastric neoplasia. The isothiocyanate (ITC) sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)butane] derived from edible crucifers such as broccoli is potently bactericidal against Helicobacter, including antibiotic-resistant strains, suggesting a possible dietary therapy. Gastric H. pylori infections express high urease activity which generates ammonia, neutralizes gastric acidity, and promotes inflammation. The finding that SF inhibits (inactivates) urease (jack bean and Helicobacter) raised the issue of whether these properties might be functionally related. The rates of inactivation of urease activity depend on enzyme and SF concentrations and show first order kinetics. Treatment with SF results in time-dependent increases in the ultraviolet absorption of partially purified Helicobacter urease in the 260-320 nm region. This provides direct spectroscopic evidence for the formation of dithiocarbamates between the ITC group of SF and cysteine thiols of urease. The potencies of inactivation of Helicobacter urease by isothiocyanates structurally related to SF were surprisingly variable. Natural isothiocyanates closely related to SF, previously shown to be bactericidal (berteroin, hirsutin, phenethyl isothiocyanate, alyssin, and erucin), did not inactivate urease activity. Furthermore, SF is bactericidal against both urease positive and negative H. pylori strains. In contrast, some isothiocyanates such as benzoyl-ITC, are very potent urease inactivators, but are not bactericidal. The bactericidal effects of SF and other ITC against Helicobacter are therefore not obligatorily linked to urease inactivation, but may reduce the inflammatory component of Helicobacter infections. PMID:23583386

  8. Celecoxib accelerates functional recovery after sciatic nerve crush in the rat

    Directory of Open Access Journals (Sweden)

    Fernández-Garza Nancy E

    2008-11-01

    Full Text Available Abstract The inflammatory response appears to be essential in the modulation of the degeneration and regeneration process after peripheral nerve injury. In injured nerves, cyclooxygenase-2 (COX-2 is strongly upregulated around the injury site, possibly playing a role in the regulation of the inflammatory response. In this study we investigated the effect of celecoxib, a COX-2 inhibitor, on functional recovery after sciatic nerve crush in rats. Unilateral sciatic nerve crush injury was performed on 10 male Wistar rats. Animals on the experimental group (n = 5 received celecoxib (10 mg/kg ip immediately before the crush injury and daily for 7 days after the injury. Control group (n = 5 received normal saline at equal regimen. A sham group (n = 5, where sciatic nerve was exposed but not crushed, was also evaluated. Functional recovery was then assessed by calculating the sciatic functional index (SFI on days 0,1,7,14 and 21 in all groups, and registering the day of motor and walking onset. In comparison with control group, celecoxib treatment (experimental group had significant beneficial effects on SFI, with a significantly better score on day 7. Anti-inflammatory drug celecoxib should be considered in the treatment of peripheral nerve injuries, but further studies are needed to explain the mechanism of its neuroprotective effects.

  9. Can celecoxib affect P-glycoprotein-mediated drug efflux? A microPET study

    NARCIS (Netherlands)

    De Vries, Erik F. J.; Doorduin, Janine; Vellinga, Namkje A. R.; Van Waarde, Aren; Dierckx, Rudi A.; Klein, Hans C.

    2008-01-01

    Introduction: P-glycoprotein (Pgp) is an efflux pump that protects vital organs like the brain from toxic substances, but which is also associated with therapy resistance. The anti-inflammatory drug celecoxib potentiates the efficacy of several cytostatic and neurotropic drugs that are known Pgp sub

  10. Bortezomib in combination with celecoxib in patients with advanced solid tumors: a phase I trial

    Directory of Open Access Journals (Sweden)

    Salzer Shanta

    2007-12-01

    Full Text Available Abstract Background COX-2 inhibitors, such as celecoxib, and ubiquitin-proteasome pathway inhibitors, such as bortezomib, can down-regulate NF-κB, a transcription factor implicated in tumor growth. The objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of bortezomib in combination with celecoxib in patients with advanced solid tumors. Methods Patients received escalating doses of bortezomib either on a weekly schedule (days 1, 8, 15, 22, and 29 repeated every 42 days or on a twice-weekly administration schedule (days 1, 4, 8, and 11 repeated every 21 days, in combination with escalating doses of celecoxib twice daily throughout the study period from 200 mg to 400 mg twice daily. Results No dose-limiting toxicity was observed during the study period. Two patients had stable disease lasting for four and five months each, and sixteen patients developed progressive disease. Conclusion The combination of bortezomib and celecoxib was well tolerated, without dose limiting toxicities observed throughout the dosing ranges tested, and will be studied further at the highest dose levels investigated. Trial registration number NCT00290680.

  11. Effect of formulation variables on preparation of celecoxib loaded polylactide-co-glycolide nanoparticles.

    Directory of Open Access Journals (Sweden)

    Dustin L Cooper

    Full Text Available Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v, drug amount (5, 10, 15, and 20 mg, and emulsifier (lecithin on nanoparticle characterization were examined for formula optimization. The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation. Nanoparticle formulations were also highly influenced by emulsifier and drug amount. Using 0.25% w/v didodecyldimethylammonium bromide NP formulations, peak zeta potential was achieved using 15 mg celecoxib with emulsifier (17.15±0.36 mV and 20 mg celecoxib without emulsifier (25.00±0.18 mV. Peak NP size reduction and entrapment efficiency was achieved using 5 mg celecoxib formulations with (70.87±1.24 nm and 95.55±0.66%, respectively and without (92.97±0.51 nm and 95.93±0.27%, respectively emulsifier. In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency. Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01. Therefore, our results suggest the use of

  12. Chemoprevention by celecoxib in reflux-induced gastric adenocarcinoma in Wistar rats that underwent gastrojejunostomy Quimioprevenção pelo celecoxibe no adenocarcinoma gástrico induzido por refluxo em ratos Wistar submetidos à gastrojejunostomia

    OpenAIRE

    Valéria Costa; Frederico Theobaldo Ramos Rocha; Laercio Gomes Lourenço; Mário Jorge Jucá; Antenor Teixeira Leal

    2009-01-01

    PURPOSE: To evaluate chemoprevention by celecoxib in cases of reflux-induced gastric adenocarcinoma, in Wistar rats that underwent gastrojejunostomy. METHODS: Sixty male Wistar rats of average age three months underwent surgery and were distributed into three groups: group 1, exploratory laparotomy; group 2, gastrojejunostomy; and group 3, gastrojejunostomy and daily celecoxib administration. After 53 weeks, the animals were sacrificed. Changes in the mucosa of the gastric body of group 1 and...

  13. Management of Helicobacter pylori infections

    NARCIS (Netherlands)

    Abadi, Amin Talebi Bezmin; Kusters, Johannes G

    2016-01-01

    BACKGROUND: Infection with Helicobacter pylori is associated with severe digestive diseases including chronic gastritis, peptic ulcer disease, and gastric cancer. Successful eradication of this common gastric pathogen in individual patients is known to prevent the occurrence of peptic ulcer disease

  14. Helicobacter pylori infection in pediatrics

    DEFF Research Database (Denmark)

    Wewer, Anne Vibeke; Kalach, Nicolas

    2003-01-01

    A high prevalence and early colonization of Helicobacter pylori infection in childhood was described again this year in developing countries in contrast to developed ones. Upper gastrointestinal endoscopy including gastric biopsies remains the diagnostic gold standard method for this infection...

  15. Agglutination of Helicobacter pylori coccoids by lectins

    Institute of Scientific and Technical Information of China (English)

    Mar Mar Khin; Jie Song Hua; Hah Cong Ng; Bow Ho; Torkel Wadstrorr

    2000-01-01

    AIM To study the agglutination pattern of Helicobacter pylori coccoid and spiral forms.METHODS Assays of agglutination and agglutination inhibition were applied using fifteen commercial lectins. RESULTS Strong agglutination was observed with mannose-specific Concanavalin A (Con A ),fucose-specific Tetragonolobus purpureas ( Lotus A ) and N-acetyl glucosamine-specific Triticum vulgaris (WGA) lectins. Mannose and fucose specific lectins were reactive with all strains of H. pylori coccoids as compared to the spirals. Specific carbohydrates, glycoproteins and mucin were shown to inhibit H. pylori lectin-agglutination reactions. Pre-treatment of the bacterial cells with formalin and sulphuric acid did not alter the agglutination patterns with lectins. However, sodium periodate treatment of bacterial cells were shown to inhibit agglutination reaction with Con A, Lotus A and WGA lectins. On the contrary, enzymatic treatment of coccoids and spirals did not show marked inhibition of H. pylori-lectin agglutination. Interestingly, heating of H.pylori cells at 60℃ for 1 hour was shown to augment the agglutination with all of the lectins tested. CONCLUSION The considerable differences in lectin agglutination patterns seen among the two differentiated forms of H. pylori might be attributable to the structural changes during theevents of morphological transformation,resulting in exposing or masking some of the sugar residues on the cell surface. Possibility of various sugar residues on the cell wall of the coccoids may allow them to bind to different carbohydrate receptors on gastric mucus and epithelial cells. The coccoids with adherence characteristics like the spirals could aid in the pathogenic process of Helicobacter infection.This may probably lead to different clinical outcome of H. pylori associated gastroduodenal disease.

  16. Primary resistance of Helicobacter pylori

    OpenAIRE

    Tepeš, Bojan; Jeverica, Samo; Ihan, Alojz; Skvarč, Miha

    2015-01-01

    Background: Antimicrobial resistance, particularly against metronidazole and clarithromycin, is the leading cause for treatment failure of Helicobacter pylori infection. Eradication rates of primary therapy have fallen below 80% in the majority of states including Slovenia. Th e aim of the study was to assess primary resistance to key antibiotics used for eradication treatment. Patients and methods: Between 2007 and 2009 we isolated 97 strains of Helicobacter pylori from the treatment naive p...

  17. Calcium Alginate and Calcium Alginate-Chitosan Beads Containing Celecoxib Solubilized in a Self-Emulsifying Phase

    OpenAIRE

    Lorena Segale; Lorella Giovannelli; Paolo Mannina; Franco Pattarino

    2016-01-01

    In this work alginate and alginate-chitosan beads containing celecoxib solubilized into a self-emulsifying phase were developed in order to obtain a drug delivery system for oral administration, able to delay the drug release in acidic environment and to promote it in the intestinal compartment. The rationale of this work was linked to the desire to improve celecoxib therapeutic effectiveness reducing its gastric adverse effects and to favor its use in the prophylaxis of colon cancer and as a...

  18. Cross-reactivity to Acetaminophen and Celecoxib According to the Type of Nonsteroidal Anti-inflammatory Drug Hypersensitivity

    OpenAIRE

    Kim, Yoon-Jeong; Lim, Kyung-Hwan; Kim, Mi-Young; Jo, Eun-Jung; Lee, Suh-Young; Lee, Seung-Eun; Yang, Min-Suk; Song, Woo-Jung; Kang, Hye-Ryun; Park, Heung-Woo; Chang, Yoon-Seok; Cho, Sang-Heon; Min, Kyung-Up; Kim, Sae-Hoon

    2013-01-01

    Purpose Identification of tolerable alternative analgesics is crucial for management in nonsteroidal anti-inflammatory drug (NSAID)-sensitive patients. We investigated cross-reactivity of acetaminophen and celecoxib according to the type of aspirin/NSAID hypersensitivity and aimed to determine the risk factors for cross-intolerance. Methods We retrospectively reviewed the medical records of patients intolerant to aspirin and NSAIDs who had undergone an acetaminophen and/or celecoxib oral prov...

  19. Promising dissolution enhancement effect of soluplus on crystallized celecoxib obtained through antisolvent precipitation and high pressure homogenization techniques.

    Science.gov (United States)

    Homayouni, Alireza; Sadeghi, Fatemeh; Varshosaz, Jaleh; Afrasiabi Garekani, Hadi; Nokhodchi, Ali

    2014-10-01

    Poor solubility and dissolution of hydrophobic drugs have become a major challenge in pharmaceutical development. Drug nanoparticles have been widely accepted to overcome this problem. The aim of this study was to manufacture celecoxib nanoparticles using antisolvent precipitation and high pressure homogenization techniques in the presence of varying concentrations of soluplus(®) as a hydrophilic stabilizer. Antisolvent crystallization followed by freeze drying (CRS-FD) and antisolvent crystallization followed by high pressure homogenization and freeze drying (HPH-FD) were used to obtain celecoxib nanoparticles. The obtained nanoparticles were analyzed in terms of particle size, saturation solubility, morphology (optical and scanning electron microscopy), solid state (DSC, XRPD and FT-IR) and dissolution behavior. The results showed that celecoxib nanoparticle can be obtained when soluplus was added to the crystallization medium. In addition, the results showed that the concentration of soluplus and the method used to prepare nanoparticles can control the size and dissolution of celecoxib. Samples obtained in the presence of 5% soluplus through HPH technique showed an excellent dissolution (90%) within 4min. It is interesting to note that celecoxib samples with high crystallinity showed better dissolution than those celecoxib samples with high amorphous content, although they had the same concentration of soluplus. DSC and XRPD proved that samples obtained via HPH technique are more crystalline than the samples obtained through only antisolvent crystallization technique. PMID:25124835

  20. Helicobacter pylori in pediatrics.

    Science.gov (United States)

    Homan, Matjaž; Hojsak, Iva; Kolaček, Sanja

    2012-09-01

    This review summarizes important pediatric studies published from April 2011 up to March 2012. Proteomics profile of ulcerogenic Helicobacter pylori strains was defined in the most interesting study of the last year. The antigen stool test is becoming the "gold standard" in prevalence studies, and according to the last epidemiologic studies, the prevalence of H. pylori infection in childhood is not decreasing any more in the developed world. The resistance rate of H. pylori strains is high in children. Therefore, among other important issues concerning H. pylori in pediatrics, guidelines published by ESPGHAN and NASPGHAN last year also recommended culture and susceptibility testing before first-line treatment in areas with high or unknown antibiotic resistance rates.

  1. Recombinant Helicobacter pylori catalase

    Institute of Scientific and Technical Information of China (English)

    Yang Bai; Ya-Li Zhang; Jian-Feng Jin; Ji-De Wang; Zhao-Shan Zhang

    2003-01-01

    AIM: To construct a recombinant strain which highly expresses catalase of Helicobacter pylori(H.pylori) and assay the activity of H. pylori catalase.METHODS: The catalase DNA was amplified from H. pylori chromosomal DNA with PCR techniques and inserted into the prokaryotie expression vector pET-22b (+), and then was transformed into the BL21 (DE3) E. coli strain which expressed catalase recombinant protein. The activity of H.pylori catalase was assayed by the Beers & Sizers.RESULTS: DNA sequence analysis showed that the sequence of catalase DNA was the same as GenBank's research. The catalase recombinant protein amounted to 24.4 % of the total bacterial protein after induced with IPTG for 3 hours at 37 ℃ and the activity of H. pylori catalase was high in the BL21 (DE3) E. coli strain.CONCLUSION: A clone expressing high activity H. pylori catalase is obtained, laying a good foundation for further studies.

  2. New Helicobacter species in humans.

    Science.gov (United States)

    Andersen, L P

    2001-01-01

    During the last decade several new Helicobacter species have been isolated from human gastric mucosa, fecal samples, liver, and gallbladder. Gastric corkscrew-shaped Helicobacter species: H. heilmannii is usually seen in the gastric foveolae in 0.2-0.6% of histological sections from the gastric mucosa of patients with dyspepsia in Western Europe, but it has only been cultured once. It is genetically and morphologically closely related to H. bizzozeronii and H. salmonis which are common in dogs and cats. It causes constantly active chronic gastritis and is regularly associated with peptic ulcer. Intestinal Helicobacter species: H. cinaedi, H. fennelliae, H. pullorum, H. westmeadii, H. canadensis, and 'H. rappini' have been isolated from patients with enteritis and proctitis. H. fennelliae, H. cinaedi, H. westmeadii, and 'H. rappini' have been isolated also from patients with septicemia. Studies indicate that H. cinaedi is transmitted from hamsters and that H. pullorum is common in chickens. 'H. rappini' has been isolated from sheep, dogs, and mice, whereas no animal reservoir has been found for H. fennelliae. Except for the cases of septicemia, none of these Helicobacter species have yet been proven to cause human disease, but they are suspected to play a role in inflammatory bowel diseases. Hepatobiliary Helicobacter species include several Helicobacter species isolated from bile and liver of animals, but only H. bilis has been isolated from the human gallbladder and H. pylori from the human liver. H. bilis has been isolated from dogs, cats, mice, and rats. Nonpylori Helicobacter species are usually difficult to culture and may be more frequently causes of human disease than realized today.

  3. Helicobacter pylori, cyclooxygenase-2 and evolution of gastric lesions: results from an intervention trial in China.

    Science.gov (United States)

    Zhang, Yang; Pan, Kai-Feng; Zhang, Lian; Ma, Jun-Ling; Zhou, Tong; Li, Ji-You; Shen, Lin; You, Wei-Cheng

    2015-12-01

    To investigate the role of cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) in the process of Helicobacter pylori-induced gastric carcinogenesis, a prospective study based on an intervention trial was conducted in Linqu County, China. A total of 1401 subjects with histopathologic diagnosis were investigated at baseline, among those, 919 completed subsequent interventions (anti-H.pylori and/or celecoxib treatment). Expressions of COX-2 and Ki-67 were assessed by immunohistochemistry, and PGE2 levels were measured by enzyme immunoassay before and after interventions, respectively. We found a grade-response relationship between COX-2 expression level and risk of advanced gastric lesions at baseline. Stratified analysis indicated an additive interaction between COX-2 expression and H.pylori infection on the elevated risk of advanced gastric lesions. The odds ratios (ORs) for both factors combined were 9.31 [95% confidence interval (CI): 4.13-20.95] for chronic atrophic gastritis, 16.26 (95% CI: 7.29-36.24) for intestinal metaplasia and 21.13 (95% CI: 7.87-56.75) for dysplasia, respectively. After interventions, COX-2 expression and Ki-67 labeling index (LI) were decreased in anti-H.pylori group (OR: 1.65, 95% CI: 1.36-1.99 for COX-2; OR: 1.78, 95% CI: 1.49-2.12 for Ki-67) or anti-H.pylori followed by celecoxib group (OR: 1.41, 95% CI: 1.17-1.70 for COX-2; OR: 1.63, 95% CI: 1.37-1.94 for Ki-67). PGE2 levels were decreased in all treatment groups. Furthermore, the regression of gastric lesions was associated with the decrease of COX-2 expression or Ki-67 LI after interventions. Our findings indicate that H.pylori-induced COX-2/PGE2 pathways play an important role on the progression of precancerous gastric lesions in a Chinese population. PMID:26449252

  4. Prospects for the use of celecoxib in patients with ankylosing spondylitis: impact on retarding disease progression

    Directory of Open Access Journals (Sweden)

    Yulia Leonidovna Korsakova

    2012-01-01

    Full Text Available Ankylosing spondylitis (AS is one of the major inflammatory diseases that affect the vertebral column and joints. The first-line drugs for the treatment of this disease are now nonsteroidal anti-inflammatory drugs (NSAIDs that not only reduce painful sensations and rigidity, but also retard the radiological progression of AS. Celecoxib is one of the effective and safe NDAIDs that are promising for the treatment of AS.

  5. In Vitro Cytotoxic Effects of Celecoxib, Mefenamic Acid, Aspirin and Indometacin on Several Cells Lines

    Science.gov (United States)

    Hashemipour, Maryam Alsadat; Mehrabizadeh Honarmand, Hoda; Falsafi, Farideh; Tahmasebi Arashlo, Mehrnaz; Rajabalian, Saied; Gandjalikhan Nassab, Sayed Amir Hossein

    2016-01-01

    Statement of the Problem Use of cyclooxygenase inhibitors as chemotherapy agents has attracted the attention of a large number of investigators in recent years. Given the importance of cancer therapy, only a limited number of studies have been carried out to investigate the effects of cyclooxygenase inhibitors on specific cell lines. Purpose This research aimed to determine the in vitro cytotoxic effects of cyclooxygenase inhibitors (COX-1 and COX-2 inhibitors) on KB, Saos-2, 1321N, U-87MG, SFBF-PI 39 cell lines. Materials and Method Powders of celecoxib, mefenamic acid, aspirin and indometacin were dissolved in the appropriate solvent. The viability of cell lines was carried out by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay technique. Data gathered from four separate experiments were expressed as mean±SD. Statistical significance was defined at p< 0.05 by using analysis of variance. Significant treatment mean values were subjected to post-hoc Tukey’s test. Results Celecoxib showed marked cytotoxic effects on KB, Saos-2, and 1321N cells, which was significant in comparison with the control group. Celecoxib was not effective in killing U-87MG cell line. Mefenamic acid exerted cytotoxic effects on KB, Saos-2, and 1321N cells, where the viability was approximately 75%. U-87MG cells were resistant to mefenamic acid. Indometacin had the highest rate of activity on U-87MG cells, which was significant in comparison with the control group. Aspirin did not exhibit any activity on these cell lines and was not effective in killing U-87MG, KB, Saos-2, and 1321N cells. Conclusion This research showed that celecoxib, indometacin, and mefenamic acid have the cytotoxic effects on KB, Saos-2, 1321N and U-87MG cell lines. Therefore, it appears that these drugs can be considered as anti-neoplastic agents in the experimental phase. PMID:27602398

  6. Helicobacter pylori infection and skin disorders.

    Science.gov (United States)

    Kutlubay, Zekayi; Zara, Tuba; Engin, Burhan; Serdaroğlu, Server; Tüzün, Yalçin; Yilmaz, Erkan; Eren, Bülent

    2014-08-01

    Helicobacter pylori is a Gram-negative bacterium that has been linked to peptic ulcer disease, gastric lymphoma, and gastric carcinoma. Apart from its well-demonstrated role in gastroduodenal diseases, some authors have suggested a potential role of Helicobacter pylori infection in several extra-intestinal pathologies including haematological, cardiovascular, neurological, metabolic, autoimmune, and dermatological diseases. Some studies suggest an association between Helicobacter pylori infection and skin diseases such as chronic idiopathic urticaria and rosacea. There have also been few case reports documenting association between Helicobacter pylori and psoriasis vulgaris, Behçet's disease, alopecia areata, Henoch-Schönlein purpura, and Sweet's syndrome. However, more systematic studies are required to clarify the proposed association between Helicobacter pylori and skin diseases; most of the studies do not show relevant relationships of these diseases with Helicobacter pylori infections. This review discusses skin diseases that are believed to be associated with Helicobacter pylori.

  7. Dose-dependent effects of celecoxib on CB-1 agonist-induced antinociception in the mice

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Zarrindast

    2009-04-01

    Full Text Available "nObjective: Endocannabinoid produce analgesia that is comparable which of opioids. The mechanism of antinociceptive effects of (∆ - 9 tetrahydrocannabinol (THC is suggested to be through cyclooxygenase (COX pathway. In the present work, the effect of two extreme dose ranges of celecoxib (mg/kg and ng/kg, a cyclooxygenase-2 (COX-2 antagonist, on arachidonylcyclopropylamide (ACPA, a selective CB1 agonist induced antinociception in mice was examined. "nMethods: We have investigated the interaction between celecoxib, at the doses of mg/kg (50, 100, 200 and 400 i.p.  and ultra low dose (ULD (25 and 50 ng/kg, i.p., on the antinociceptive effect of intracerebroventricular (i.c.v. administration of ACPA (0.004, 0.0625 and 1 μg/mice, using formalin test in mice. "nResults: I.C.V. administration of ACPA induced antinociception. Intraperitoneal administration of celecoxib (mg/kg and its ULD (ng/kg attenuated and potentiated, ACPA antinociceptive effects, respectively. "nConclusion: It is concluded that the mg/kg doses of COX-2 antagonist showed opposite effects compare to the ultra-low dose of the drug.

  8. Comparative study of liposomes, transfersomes and ethosomes as carriers for improving topical delivery of celecoxib.

    Science.gov (United States)

    Bragagni, Marco; Mennini, Natascia; Maestrelli, Francesca; Cirri, Marzia; Mura, Paola

    2012-01-01

    Topical administration of celecoxib proved to be an effective mean of preventing skin cancer development and improving anticancer drugs effectiveness in skin tumors treatment. The aim of this study was the development of an effective topical formulation of celecoxib, able to promote drug skin delivery, providing its in depth penetration through the skin layers. Three kinds of vesicular formulations have been investigated as drug carriers: liposomes containing a surfactant, or transfersomes and ethosomes, containing suitable edge activators. Firstly, the effect of membrane composition variations on the system performance has been evaluated for each vesicle type. Selected formulations were characterized for particle size, polydispersity index and encapsulation efficiency. The best formulations were subjected to ex vivo permeation studies through excised human skin. All vesicular formulations markedly (p ethosomes, respectively. In particular, ethosomes containing Tween 20 as edge activator not only showed the best vesicle dimensions and homogeneity, and the highest encapsulation efficacy (54.4%), but also enabled the highest increase in drug penetration through the skin, probably due to the simultaneous presence in their composition of ethanol and Tween 20, both acting as permeation enhancers. Therefore, among the various vesicular formulations examined in the study, Tween 20-ethosomes can be considered the most promising one as carrier for topical celecoxib applications aimed to prevent skin cancer development and increase the anticancer drugs effectiveness against skin tumors. PMID:23043648

  9. Comparative study of liposomes, transfersomes and ethosomes as carriers for improving topical delivery of celecoxib.

    Science.gov (United States)

    Bragagni, Marco; Mennini, Natascia; Maestrelli, Francesca; Cirri, Marzia; Mura, Paola

    2012-01-01

    Topical administration of celecoxib proved to be an effective mean of preventing skin cancer development and improving anticancer drugs effectiveness in skin tumors treatment. The aim of this study was the development of an effective topical formulation of celecoxib, able to promote drug skin delivery, providing its in depth penetration through the skin layers. Three kinds of vesicular formulations have been investigated as drug carriers: liposomes containing a surfactant, or transfersomes and ethosomes, containing suitable edge activators. Firstly, the effect of membrane composition variations on the system performance has been evaluated for each vesicle type. Selected formulations were characterized for particle size, polydispersity index and encapsulation efficiency. The best formulations were subjected to ex vivo permeation studies through excised human skin. All vesicular formulations markedly (p ethosomes, respectively. In particular, ethosomes containing Tween 20 as edge activator not only showed the best vesicle dimensions and homogeneity, and the highest encapsulation efficacy (54.4%), but also enabled the highest increase in drug penetration through the skin, probably due to the simultaneous presence in their composition of ethanol and Tween 20, both acting as permeation enhancers. Therefore, among the various vesicular formulations examined in the study, Tween 20-ethosomes can be considered the most promising one as carrier for topical celecoxib applications aimed to prevent skin cancer development and increase the anticancer drugs effectiveness against skin tumors.

  10. Chrysin alleviates testicular dysfunction in adjuvant arthritic rats via suppression of inflammation and apoptosis: Comparison with celecoxib

    Energy Technology Data Exchange (ETDEWEB)

    Darwish, Hebatallah A. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Arab, Hany H., E-mail: hany.arab@pharma.cu.edu.eg [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Abdelsalam, Rania M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt)

    2014-09-01

    Long standing rheumatoid arthritis (RA) is associated with testicular dysfunction and subfertility. Few studies have addressed the pathogenesis of testicular injury in RA and its modulation by effective agents. Thus, the current study aimed at evaluating the effects of two testosterone boosting agents; chrysin, a natural flavone and celecoxib, a selective COX-2 inhibitor, in testicular impairment in rats with adjuvant arthritis, an experimental model of RA. Chrysin (25 and 50 mg/kg) and celecoxib (5 mg/kg) were orally administered to Wistar rats once daily for 21 days starting 1 h before arthritis induction. Chrysin suppressed paw edema with comparable efficacy to celecoxib. More important, chrysin, dose-dependently and celecoxib attenuated the testicular injury via reversing lowered gonadosomatic index and histopathologic alterations with preservation of spermatogenesis. Both agents upregulated steroidogenic acute regulatory (StAR) mRNA expression and serum testosterone with concomitant restoration of LH and FSH. Furthermore, they suppressed inflammation via abrogation of myeloperoxidase, TNF-α and protein expression of COX-2 and iNOS besides elevation of IL-10. Alleviation of the testicular impairment was accompanied with suppression of oxidative stress via lowering testicular lipid peroxides and nitric oxide. With respect to apoptosis, both agents downregulated FasL mRNA expression and caspase-3 activity in favor of cell survival. For the first time, these findings highlight the protective effects of chrysin and celecoxib against testicular dysfunction in experimental RA which were mediated via boosting testosterone in addition to attenuation of testicular inflammation, oxidative stress and apoptosis. Generally, the 50 mg/kg dose of chrysin exerted comparable protective actions to celecoxib. - Highlights: • Chrysin and celecoxib alleviated testicular suppression in adjuvant arthritis. • They attenuated histopathological damage and preserved spermatogenesis

  11. Destruction of vasculogenic mimicry channels by targeting epirubicin plus celecoxib liposomes in treatment of brain glioma

    Directory of Open Access Journals (Sweden)

    Ju RJ

    2016-03-01

    Full Text Available Rui-Jun Ju,1,2,* Fan Zeng,1,* Lei Liu,1 Li-Min Mu,1 Hong-Jun Xie,1 Yao Zhao,1 Yan Yan,1 Jia-Shuan Wu,1 Ying-Jie Hu,1 Wan-Liang Lu1 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 2Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: The efficacy of chemotherapy for brain glioma is restricted by the blood–brain barrier (BBB, and surgery or radiotherapy cannot eliminate the glioma cells because of their unique location. Residual brain glioma cells can form vasculogenic mimicry (VM channels that can cause a recurrence of brain glioma. In the present study, targeting liposomes incorporating epirubicin and celecoxib were prepared and used for the treatment of brain glioma, along with the destruction of their VM channels. Evaluations were performed on the human brain glioma U87MG cells in vitro and on intracranial brain glioma-bearing nude mice. Targeting epirubicin plus celecoxib liposomes in the circulatory blood system were able to be transported across the BBB, and accumulated in the brain glioma region. Then, the liposomes were internalized by brain glioma cells and killed glioma cells by direct cytotoxic injury and the induction of apoptosis. The induction of apoptosis was related to the activation of caspase-8- and -3-signaling pathways, the activation of the proapoptotic protein Bax, and the suppression of the antiapoptotic protein Mcl-1. The destruction of brain glioma VM channels was related to the downregulation of VM channel-forming indictors, which consisted of MMP-2, MMP-9, FAK, VE-Cad, and VEGF. The results demonstrated that the targeting epirubicin plus celecoxib liposomes were able to effectively destroy the glioma VM channels and exhibited significant efficacy in the

  12. Effect of frequent consumption of a Lactobacillus casei-containing milk drink in Helicobacter pylori-colonized subjects.

    NARCIS (Netherlands)

    Cats, A.; Kuipers, E.J.; Bosschaert, MA; Pot, RG; Vandenbroucke-Grauls, C.M.J.E.; Kusters, J.G.

    2003-01-01

    BACKGROUND: Several studies have reported inhibitory effects of lactic acid bacteria on bacterial pathogens. AIM: To test whether a drink containing Lactobacillus casei strain Shirota inhibits Helicobacter pylori growth. METHODS: The in vitro growth inhibition of H. pylori was studied when L. casei

  13. Nitroimidazole resistance in Helicobacter pylori

    NARCIS (Netherlands)

    Van der Wouden, EJ; Thijs, JC; Van Zwet, AA; Kleibeuker, JH

    2000-01-01

    The efficacy of a nitroimidazole-containing regimen for the treatment of Helicobacter pylori infection is decreased by nitroimidazole resistance. Nitroimidazoles are metabolized by H. pylori by several nitro-reductases of which an oxygen-insensitive NADPH nitroreductase encoded by the rdxA gene is t

  14. Helicobacter pylori and Peptic Ulcers

    Centers for Disease Control (CDC) Podcasts

    2010-08-17

    In this podcast, CDC's Dr. David Swerdlow discusses the relationship between Helicobacter pylori and peptic ulcer disease and trends in hospitalization rates for peptic ulcer disease in the United States between 1998 and 2005.  Created: 8/17/2010 by National Center for Emerging and Zoonotic Infectious Diseases.   Date Released: 8/17/2010.

  15. Halitosis and Helicobacter pylori infection

    NARCIS (Netherlands)

    Tangerman, A.; Winkel, E. G.; de Laat, L.; van Oijen, A. H.; de Boer, W. A.

    2012-01-01

    There is disagreement about a possible relationship between Helicobacter pylori (H. pylori) infection and objective halitosis, as established by volatile sulfur compounds (VSCs) in the breath. Many studies related to H. pylori used self-reported halitosis, a subjective and unreliable method to detec

  16. Nickel Homeostasis in Helicobacter Species

    NARCIS (Netherlands)

    J. Stoof (Jeroen)

    2011-01-01

    textabstractGastric Helicobacter species are adapted to colonize the acidic environment of the stomach. Colonization with H pylori is life long if untreated, and can lead to gastritis, peptic ulcer disease and eventually to gastric cancer. Although H pylori is sensitive to many antibiotics in vitro,

  17. Celecoxib, but not indomethacin, ameliorates the hypertensive and perivascular fibrotic actions of cyclosporine in rats: Role of endothelin signaling

    Energy Technology Data Exchange (ETDEWEB)

    El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com [Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University (Egypt); Helmy, Maged W. [Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University (Egypt); Ali, Rabab M.; El-Gowelli, Hanan M. [Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University (Egypt)

    2015-04-01

    The immunosuppressant drug cyclosporine (CSA) is used with nonsteroidal antiinflammatory drugs (NSAIDs) in arthritic conditions. In this study, we investigated whether NSAIDs modify the deleterious hypertensive action of CSA and the role of endothelin (ET) receptors in this interaction. Pharmacologic, protein expression, and histopathologic studies were performed in rats to investigate the roles of endothelin receptors (ET{sub A}/ET{sub B}) in the hemodynamic interaction between CSA and two NSAIDs, indomethacin and celecoxib. Tail-cuff plethysmography measurements showed that CSA (20 mg kg{sup −1} day{sup −1}, 10 days) increased systolic blood pressure (SBP) and heart rate (HR). CSA hypertension was associated with renal perivascular fibrosis and divergent changes in immunohistochemical signals of renal arteriolar ET{sub A} (increases) and ET{sub B} (decreases) receptors. While these effects of CSA were preserved in rats treated concomitantly with indomethacin (5 mg kg{sup −1} day{sup −1}), celecoxib (10 mg kg{sup −1} day{sup −1}) abolished the pressor, tachycardic, and fibrotic effects of CSA and normalized the altered renal ET{sub A}/ET{sub B} receptor expressions. Selective blockade of ET{sub A} receptors by atrasentan (5 mg kg{sup −1} day{sup −1}) abolished the pressor response elicited by CSA or CSA plus indomethacin. Alternatively, BQ788 (ET{sub B} receptor blocker, 0.1 mg kg{sup −1} day{sup −1}) caused celecoxib-sensitive elevations in SBP and potentiated the pressor response evoked by CSA. Together, the improved renovascular fibrotic and endothelin receptor profile (ET{sub A} downregulation and ET{sub B} upregulation) mediate, at least partly, the protective effect of celecoxib against the hypertensive effect of CSA. Clinically, the use of celecoxib along with CSA in the management of arthritic conditions might provide hypertension-free regimen. - Highlights: • Chronic CSA causes hypertension and renal perivascular fibrosis in rats.

  18. Celecoxib treatment does not alter recruitment and activation of osteoclasts in the initial phase of experimental tooth movement

    Science.gov (United States)

    Carvalho-Filho, E.P.; Stabile, A.C.; Ervolino, E.; Stuani, M.B.S.; Iyomasa, M.M.; Rocha, M.J.A.

    2012-01-01

    In a previous study, we reported that the short-term treatment with celecoxib, a non-steroidal anti-inflammatory drug (NSAID) attenuates the activation of brain structures related to nociception and does not interfere with orthodontic incisor separation in rats. The conclusion was that celecoxib could possibly be prescribed for pain in orthodontic patients. However, we did not analyze the effects of this drug in periodontium. The aim of this follow-up study was to analyze effects of celecoxib treatment on recruitment and activation of osteoclasts and alveolar bone resorption after inserting an activated orthodontic appliance between the incisors in our rat model. Twenty rats (400–420 g) were pretreated through oral gavage with celecoxib (50 mg/kg) or vehicle (carboxymethyl-cellulose 0.4%). After 30 min, they received an activated (30 g) orthodontic appliance, set not to cause any palate disjunction. In sham animals, the appliance was immediately removed after introduction. All animals received ground food and, every 12 h, celecoxib or vehicle. After 48 h, they were anesthetized and transcardiacally perfused through the aorta with 4% formaldehyde. Subsequently, maxillae were removed, post-fixed and processed for histomorphometry or immunohistochemical analyses. As expected, incisor distalization induced an inflammatory response with certain histological changes, including an increase in the number of active osteoclasts at the compression side in group treated with vehicle (appliance:32.2±2.49 vs sham: 4.8±1.79, P<0.05) and celecoxib (appliance: 31.0±1.45 vs sham: 4.6±1.82, P<0.05). The treatment with celecoxib did not modify substantially the histological alterations and the number of active osteoclasts after activation of orthodontic appliance. Moreover, we did not see any difference between the groups with respect to percentage of bone resorption area. Taken together with our previous results we conclude that short-term treatment with celecoxib can indeed be

  19. In situ formed suspensions for local sustained action of celecoxib following intra-articular administration

    DEFF Research Database (Denmark)

    Larsen, Susan Weng; Frost, Anna Buus; Østergaard, Jesper;

    an in situ formed suspension of celecoxib. In the field of IA drug administration the in situ suspension forming drug delivery principle appears promising for the provision of local prolonged drug action. However, for clinical use the reproducibility of the precipitation step in the biological matrix...... situ formed suspension exhibited an aqueous solubility similar to that of parent celecoxib used for the preformed aqueous suspension. Results from the in vivo experiments in horses revealed that solid materials  as observed within the synovium of the radiocarpal joint 10 days after IA administration of...

  20. Effects of celecoxib on acid-challenged gastric mucosa of rats: comparison with metamizol and piroxicam.

    Science.gov (United States)

    Berenguer, Bettina; Alarcón De La Lastra, Catalina; Motilva, Virginia; La Casa, Carmen; Herrerias, Juan Manuel; Pozo, David; Calero, María José Martin

    2004-06-01

    Selective COX-2 inhibitors have been shown to produce fewer gastrointestinal adverse reactions than classical NSAIDs. Nevertheless, these new agents may worsen and delay the healing of experimentally induced gastric ulcers in animals. In this study, we compared the effects of a selective COX-2 inhibitor (celecoxib), a preferential COX-1 inhibitor (piroxicam), and a nonnarcotic analgesic (metamizol) on normal gastric mucosa of rats and, on the other hand, in a setting of preexisting acute gastric lesions induced by 0.6 N hydrochloric acid. Under normal conditions, only piroxicam produced appreciable gastric lesions. However, after acid challenge the three assayed drugs induced significant macroscopic and microscopic damage. Myeloperoxidase activity as an index of neutrophil infiltration was elevated with celecoxib and piroxicam on normal gastric mucosa. On inflamed mucosa, celecoxib augmented enzymatic activity at the lower dose, which was parallelled by an increase in the interleukin 1beta level. Acid instillaton produced a significant rise in PGE2 content at 7 hr. Drug treatment after acid challenge decreased prostaglandin values in all cases, although to a lesser extent than after single drug dose administration. COX-2 mRNA expression was visible 1 hr after acid application, whereas COX-2 protein could only be detected at 7 hr. Piroxicam increased both expression levels. All NSAIDs enhanced transforming growth factor alpha and epidermal growth factor receptor immunoreactivity around the acid-induced lesions. It is concluded that selective COX-2 inhibitors, like conventional NSAIDs, impair the healing of gastric damage, and therefore special attention should be paid in patients with gastric pathologies.

  1. Effect of adding celecoxib to a single dose of gabapentin on postoperative pain relief

    Directory of Open Access Journals (Sweden)

    Mansour Choubsaz

    2015-01-01

    Full Text Available Background: In recent years, several studies with conflicting results have been done on the role of gabapentin and non-steroidal anti-inflammatory drugs in pre-emptive analgesia to control postoperative pain. The purpose of this study was to evaluate the effect of adding low doses of celecoxib to gabapentin on increasing the analgesic effect and patients’ satisfaction. Methods: In this double-blind randomized clinical trial, 130 patients with ASA I, II class were divided in two groups as they were the candidates for elective inguinal hernia surgery with spinal anesthesia. Before the surgery, the control group (G received 300 mg oral dose of gabapentin and the study group (GC received 100 mg celecoxib in addition to the above dose. Severity of patients’ pain was measured using the visual analogue scale (VAS. By the same token, the amount of painkillers usedwas measured and statistically analyzed. Results: The results suggested a statistically significant difference between the two groups in terms of pain level 4, 6 and 24 hours after surgery (P<0.05. Adding low-dose of celeoxib to gabapentin before the surgery and the combination of these two drugs caused further reduction of pain 4, 6 and 24 h after the surgery in comparison to the administration of gabapentin alone. Conclusion: Adding 100 mg celecoxib to 300 mg gabapentin resulted in a reduction of pain level 24 h after elective surgery of inguinal hernia in patients of control group (P<0.05. However, in terms of using painkillers (analgesics, there was no statistically significant difference between the two groups.

  2. Response surface methodology for the optimization of celecoxib self-microemulsifying drug delivery system

    OpenAIRE

    Shaji Jessy; Lodha Shital

    2008-01-01

    The aim of the present study was to prepare, evaluate and optimize, self micro emulsifying drug delivery system of celecoxib. A 3 factor, 3 level factorial design was used for the optimization procedure with different amounts of Labrafil 2609 WL, Labrasol, and Cremophor EL as the independent variables. The response variable was selected on particle size (nm) of the droplets after dilution in 0.1N HCl. Particle size of the self micro-emulsifying drug delivery system depends on the quantity of ...

  3. Celecoxib and sulfasalazine had negative association with coronary artery diseases in patients with ankylosing spondylitis

    Science.gov (United States)

    Wu, Li-Chih; Leong, Pui-Ying; Yeo, Kai-Jieh; Li, Ting-Yu; Wang, Yu-Hsun; Chiou, Jeng-Yuan; Wei, James Cheng-Chung

    2016-01-01

    Abstract The aim of the study is to assess the effects of celecoxib and sulfasalazine on the risk of coronary artery disease (CAD) in patients with ankylosing spondylitis (AS). Using the claims data of Taiwan National Health Insurance (NHI) database, a nationally representative data that contain the medical records of 23 million Taiwan residents, we randomly selected 1 million cohort from the database, and then we enrolled only patients who were newly diagnosed with AS (n = 4829) between year 2001 and 2010, excluding patients who had CAD (ICD-9- CM codes: 410–414) before the diagnosis of AS (n = 4112). According to propensity score matched 1:2 on age, gender, AS duration, Charlson comorbidity index, hypertension, and hyperlipidemia, 236 and 472 patients were included in the case (AS with CAD) and control (AS without CAD) groups, respectively. We used the WHO defined daily dose (DDD) as a tool to assess the dosage of sulfasalazine and celecoxib exposure. Conditional logistic regression was used to estimate the crude and adjusted odds ratios (ORs) and 95% confidence interval (CI) for the risk of CAD associated with use of sulfasalazine and celecoxib. Among 4112 AS patients, 8.4% (346/4112) developed CAD. CAD in AS patients were positively associated with age of 35 to 65, Charlson comorbidities index (CCI), hypertension, and hyperlipidemia. There was no gender difference between case and control groups. After adjustment for age, gender, CCI, hypertension, and hyperlipidemia, sulfasalazine users with an average daily dose ≥ 0.5 DDD (0.5 gm/day) had negative association with CAD events as compared to sulfasalazine nonusers (OR 0.63; 95% CI, 0.40–0.99, P  1.5 DDD, were negatively associated with CAD events, compared to celecoxib nonusers (OR 0.34; 95% CI, 0.13–0.89; P < 0.05). In this 10-year population-based case-control study, 8.4% of AS patients developed CAD. Sulfasalazine usage at an average dose of ≥ 0.5 gm/day demonstrated negative association

  4. 塞来昔布对胃癌SGC7901细胞放射敏感性的实验研究%Radiation enhancement of celecoxib on gastrical SGC7901 cell line

    Institute of Scientific and Technical Information of China (English)

    何信佳; 宫文静; 安永恒

    2011-01-01

    OBJECTIVE: To investigate the radiosensitivity enhancement effect of cyclooxygenase-2 (COX-2) inhibitor celecoxib on gastric cancer cells in vitro and to initially disclosure its mechanism. METHODS.. MTT assay was used to measure the proliferation inhibition of celecoxib on SGC?901 cells and determine the concentration IC50. The clonogenic assay was performed to determine the radiosensitizing effect of celecoxib on gastric cancer cells with the concentration of 20% IC50. The cell cycle distribution was analyzed by flow cytometry (FCM). RESULTS: Inhibition of cell proliferation seemed more dependent on the dose and the time. The IC50 of 48 h was 34.38 μmol/L.The group of radiation combined with celecoxib displayed the value of SF2, D0, Dq, SER was significantly lower than those of radiation alone group. Cell cycle analysis showed that the cell population in G2/M phase increased and in S phase decreased.CONCLUSIONS: COX-2 inhibitor celecoxib can obviously enhance the radiosensitivity of SGC7901 cells, which is probably associated with the inhibition of sublethal damage of tumor cells and facilitation of redistribution of tumor cell cycle.%目的:探讨环氧合酶2(COX-2)抑制剂塞来昔布对胃癌SGC7901细胞株的放射增敏作用及其机制.方法:MTT法检测塞来昔布对胃癌SGC7901细胞株的抑制作用,计算出塞来昔布的半数抑制浓度(IC50);克隆形成实验用于检测20%IC50这个浓度的塞来昔布对胃癌SGC细胞是否具有放射敏感性;流式细胞术(FCM)分析细胞周期的分布情况.结果:MTT实验显示塞来昔布对SGC7901细胞株的抑制率随浓度的升高而升高,48 h的IC50是34.38 μmol/L;克隆形成实验显示,照射组+药物组与单纯照射组相比,反映放射敏感性指标的存活分数(SF2)、平均致死荆量(DO)及准阈剂量(Dq)均下降,放射增敏比(SER)升高.FCM检测细胞周期G2和M期细胞比例增加,S期细胞比例减少.结论:塞来昔布能增加胃癌SGC7901细胞的

  5. Gastric and enterohepatic helicobacters other than Helicobacter pylori.

    Science.gov (United States)

    Ménard, Armelle; Péré-Védrenne, Christelle; Haesebrouck, Freddy; Flahou, Bram

    2014-09-01

    During the past year, research on non-Helicobacter pylori species has intensified. H. valdiviensis was isolated from wild birds, and putative novel species have been isolated from Bengal tigers and Australian marsupials. Various genomes have been sequenced: H. bilis, H. canis, H. macacae, H. fennelliae, H. cetorum, and H. suis. Several studies highlighted the virulence of non-H. pylori species including H. cinaedi in humans and hyperlipidemic mice or H. macacae in geriatric rhesus monkeys with intestinal adenocarcinoma. Not surprisingly, increased attention has been paid to the position of Helicobacter species in the microbiota of children and animal species (mice, chickens, penguins, and migrating birds). A large number of experimental studies have been performed in animal models of Helicobacter induced typhlocolitis, showing that the gastrointestinal microbial community is involved in modulation of host pathways leading to chronic inflammation. Animal models of H. suis, H. heilmannii, and H. felis infection have been used to study the development of severe inflammation-related pathologies, including gastric MALT lymphoma and adenocarcinoma.

  6. Helicobacter pylori infection in pediatrics

    DEFF Research Database (Denmark)

    Wewer, Anne Vibeke; Kalach, Nicolas

    2003-01-01

    A high prevalence and early colonization of Helicobacter pylori infection in childhood was described again this year in developing countries in contrast to developed ones. Upper gastrointestinal endoscopy including gastric biopsies remains the diagnostic gold standard method for this infection. A...... place only after susceptibility testing. The association of a proton pump inhibitor and two antibiotics for 1 or 2 weeks gives the best eradication rates. The crucial question to elucidate is whether asymptomatic children should be treated to prevent cancer in the future.......A high prevalence and early colonization of Helicobacter pylori infection in childhood was described again this year in developing countries in contrast to developed ones. Upper gastrointestinal endoscopy including gastric biopsies remains the diagnostic gold standard method for this infection...

  7. Canadian Helicobacter pylori Consensus Conference

    OpenAIRE

    Hunt, Richard; Thomson, Alan BR

    1998-01-01

    These guidelines were created to dispel confusion and provide guidance about how the isolation of Helicobacter pylori infection has led to new opportunities and initiatives to improve patient care. The guidelines are designed for practical application in management decisions, but must remain flexible and amenable to change with new information. Updated versions of the recommendations are anticipated. Although it is now clear that H pylori is a major gastrointestinal pathogen, the extent of th...

  8. Helicobacter pylori infection in children

    Directory of Open Access Journals (Sweden)

    Rajindrajith Shaman

    2009-01-01

    Full Text Available Helicobacter pylori infection is a common problem in pediatric practice, and its acquisition is related with poor socioeconomic conditions. Although the organism is thought to be responsible for many diseases, only a handful of them have a direct causal relationship. At present, only a small number of children with well-defined clinical syndromes are benefited from testing and treatment. The treatment should include at least two antibiotics with a proton pump inhibitor.

  9. Management of Helicobacter pylori infections

    OpenAIRE

    Abadi, Amin Talebi Bezmin; Kusters, Johannes G.

    2016-01-01

    Background Infection with Helicobacter pylori is associated with severe digestive diseases including chronic gastritis, peptic ulcer disease, and gastric cancer. Successful eradication of this common gastric pathogen in individual patients is known to prevent the occurrence of peptic ulcer disease and gastric cancer. Discussion With half of the world’s population being infected with H, pylori and only few antibiotics result in an effective eradication, a successful antibiotic driven worldwide...

  10. Helicobacter pylori and pancreatic diseases

    OpenAIRE

    Bulajic, Milutin; Panic, Nikola; Löhr, Johannes Matthias

    2014-01-01

    A possible role for Helicobacter pylori (H. pylori) infection in pancreatic diseases remains controversial. H. pylori infection with antral predomination leading to an increase in pancreatic bicarbonate output and inducing ductal epithelial cell proliferation could contribute to the development of pancreatic cancer via complex interactions with the ABO genotype, dietary and smoking habits and N-nitrosamine exposure of the host. Although the individual study data available so far is inconsiste...

  11. Preparation and evaluation of electrospun nanofibers containing pectin and time-dependent polymers aimed for colonic drug delivery of celecoxib

    Directory of Open Access Journals (Sweden)

    A. Akhgari

    2016-01-01

    Full Text Available Objective(s:The aim of this study was to prepare electrospun nanofibers of celecoxib using combination of time-dependent polymers with pectin to achieve a colon-specific drug delivery system for celecoxib. Materials and Methods:Formulations were produced based on two multilevel 22 full factorial designs. The independent variables were the ratio of drug:time-dependent polymer (X1 and the amount of pec­tin in formulations (X2. Electrospinning process was used for preparation of nanofibers. The spinning solutions were loaded in 5 mL syringes. The feeding rate was fixed by a syringe pump at 2.0 mL/h and a high voltage supply at range 10-18 kV was applied for electrospinning. Electrospun nanofibers were collected and evaluated by scanning electron microscopy and drug release in the acid and buffer with pH 6.8 with and without pectinase. Results:Electrospun nanofibers of celecoxib with appropriate morphological properties were produced via electrospinning process. Drug release from electrospun nanofibers was very low in the acidic media; while, drug release in the simulated colonic media was the highest from formulations containing pectin. Conclusion: Formulation F2 (containing drug:ERS with the ratio of 1:2 and 10% pectin exhibited acceptable morphological characteristics and protection of drug in the upper GI tract and could be a good candidate as a colonic drug delivery system for celecoxib.

  12. Helicobacter spp. other than H. pylori.

    Science.gov (United States)

    Rossi, Mirko; Hänninen, Marja-Liisa

    2012-09-01

    Significant advances have been made over the last 12 months in the understanding of the biology of non-H. pylori Helicobacter species (NHPH). Several studies have investigated the association between NHPH and human disease, including Crohn's disease, lithiasis, liver disease, coronary disease, gastritis, and pyoderma gangrenosum-like ulcers. Novel Helicobacter taxa were identified in new vertebrate hosts, and new methodologies in the fields of identification of Helicobacter spp. and evaluation of antibiotic resistance were described. The genome of the first human-derived gastric NHPH strain (Helicobacter bizzozeronii CIII-1) was sequenced, and several studies elucidated functions of different genes in NHPH. A number of important investigations regarding pathogenesis and immunopathobiology of NHPH infections have been published including the description of a new urease in Helicobacter mustelae. Finally, the effects of the gut microbiota and probiotics on NHPH infections were investigated.

  13. [Helicobacter pylori and Arteriosclerosis].

    Science.gov (United States)

    Matsui, Teruaki

    2011-03-01

    Helicobacter pylori (H. pylori) infection-related diseases are known to include gastritis, gastric and duodenal ulcer, gastric cancer, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, iron-deficient anemia, urticaria, reflux esophagitis, and some lifestyle-related diseases. It is indicated that homocysteine involved with arteriosclerosis induces lifestyle-related diseases. Homocysteine is decomposed to methionine and cysteine (useful substances) in the liver, through the involvement of vitamin B₁₂ (VB₁₂) and folic acid. However, deficiency of VB₁₂ and folic acid induces an increase in unmetabolized homocysteine stimulating active oxygen and promoting arteriosclerosis. VB₁₂ and folic acid are activated by the intrinsic factors of gastric parietal cells and gastric acid. The question of whether homocysteine, as a trigger of arteriosclerosis, was influenced by H. pylori infection was investigated. H. pylori infection induces atrophy of the gastric mucosa, and the function of parietal cells decreases with the atrophy to inactivate its intrinsic factor. The inactivation of the intrinsic factor causes a deficiency of VB₁₂ and folic acid to increase homocysteine's chances of triggering arteriosclerosis. The significance and usefulness of H. pylori eradication therapy was evaluated for its ability to prevent arteriosclerosis that induces lifestyle-related diseases. Persons with positive and negative results of H. pylori infection were divided into a group of those aged 65 years or more (early and late elderly) and a group of those under 65 years of age, and assessed for gastric juice. For twenty-five persons from each group who underwent gastrointestinal endoscopy, the degree of atrophy of the gastric mucosa was observed. Blood homocysteine was measured as a novel index of arteriosclerosis, as well as VB₁₂ and folic acid that affect the metabolism of homocysteine, and then activated by gastric acid and intrinsic factors. Their

  14. A Rapid and Sensitive HPLC Method for the Analysis of Celecoxib in Human Plasma: Application to Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    A Ajami

    2008-09-01

    Full Text Available Background and the purpose of the study: A suitable high-performance liquid chromatography (HPLC method for determination of celecoxib levels in plasma is of prime need for the pharmacokinetics and bioequivalence studies of celecoxib preparations. The present study describes a simple, rapid, sensitive, reliable, and economic HPLC method for determination of celecoxib in human plasma which is more feasible than reported celecoxib HPLC assays. Methods: The drug and internal standard were extracted using n-hexane /isoamyl alcohol (97:3 and analyzed on a C18 µ-Bondapak HPLC column with KH2PO4 (0.01M, pH= 4 - acetonitrile (60:40 as the mobile phase, at 260 nm. The method involved simple one-step liquid-liquid extraction procedure with extraction recovery of greater than 90%. Results:  The standard curve covering 0.01-2.0 μg/ml concentration range was linear. The coefficients of variation and relative errors for inter- and intra-day assay ranged from 5.67 to 9.83 and 0.35 to 7.89 %, respectively. Conclusions: HPLC assay was performed isocratically on a reversed-phase column with UV detection. By this method a limit of quantification of 10 ng/ml of a sample size of 0.5 ml is achieved which is comparable or even better than the reported methods. The developed method was applied to the analysis of celecoxib levels in plasma collected from healthy volunteers who participated in a pharmacokinetic study.

  15. Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial

    OpenAIRE

    James, Nicholas D.; Sydes, Matthew R.; Mason, Malcolm D; Clarke, Noel W; Anderson, John; Dearnaley, David P; Dwyer, John; Jovic, Gordana; Ritchie, Alastair WS; Russell, J Martin; Sanders, Karen; Thalmann, George N; Bertelli, Gianfilippo; Birtle, Alison J; O'Sullivan, Joe M

    2012-01-01

    Summary Background Long-term hormone therapy alone is standard care for metastatic or high-risk, non-metastatic prostate cancer. STAMPEDE—an international, open-label, randomised controlled trial—uses a novel multiarm, multistage design to assess whether the early additional use of one or two drugs (docetaxel, zoledronic acid, celecoxib, zoledronic acid and docetaxel, or zoledronic acid and celecoxib) improves survival in men starting first-line, long-term hormone therapy. Here, we report the...

  16. Additional effect of metformin and celecoxib against lipid dysregulation and adipose tissue inflammation in high-fat fed rats with insulin resistance and fatty liver.

    Science.gov (United States)

    Lu, Chieh-Hua; Hung, Yi-Jen; Hsieh, Po-Shiuan

    2016-10-15

    We investigated the effects of metformin and celecoxib on obesity-induced adipose tissue inflammation, insulin resistance (IR), fatty liver, and high blood pressure in high-fat (HF) fed rats. Male Sprague-Dawley rats were fed with either regular or HF diet for 8 weeks. Rats fed with regular diet were treated with vehicle for further 4 weeks. HF fed rats were divided into 6 groups, namely, vehicle, celecoxib (30mg/kg/day), metformin (300mg/kg/day), metformin (150mg/kg/day), metformin (300mg/kg/day) with celecoxib (30mg/kg/day), and metformin (150mg/kg/day) with celecoxib (15mg/kg/day) for additional 4 weeks. Increased body weight in HF fed rats was significantly reduced by metformin alone and metformin combined with celecoxib. The increases in the HOMA-IR value and the area under the curve of glucose following an oral glucose tolerance test, systolic blood pressure, and adipocyte size were significantly diminished in treated rats, especially rats undergoing combined treatment. Treatments with either celecoxib or in combination with metformin resulted in a reduction in AT macrophage infiltration and decreases in levels of adipose tissue TNF-α, MCP-1, and leptin levels in high-fat (HF) fed rats. Furthermore, the elevated hepatic triglycerides content was significantly decreased in the combined treatment group compared to that of groups of celecoxib or metformin alone. Celecoxib exerts a synergistic beneficial effect with metformin on and obesity-associated metabolic and cardiovascular disorders in high-fat fed rats.

  17. 塞来昔布对骨关节炎大鼠疼痛评分和SP表达的影响%The role of celecoxib to pain scores and substance P in osteoarthritis rat model

    Institute of Scientific and Technical Information of China (English)

    郑颖; 常新; 刘存明; 范薇; 刘奕; 张钧

    2013-01-01

    substance P in osteoarthritis group (Group C and D) were significantly greater than those in control group (P<0.01);Substance P content in dorsal root ganglion and serum in osteoarthritis group was positively correlated with pain scores (r=0.83, P<0.01;r=0.61, P<0.01);The level of substance P content and pain scores were significantly decreased by celecoxib in Group D (P<0.05). Conclusion substance P plays an important role in occurrence of pain in osteoarthritis. Celecoxib can inhibit the production of substance P in serum and DRG and ameliorate pain.

  18. Antigen epitope of Helicobacter pylorivacuolating cytotoxin A

    Institute of Scientific and Technical Information of China (English)

    Xiu-Li Liu; Shu-Qin Li; Chun-Jie Liu; Hao-Xia Tao; Zhao-Shan Zhang

    2004-01-01

    AIM: To construct and select antigen epitopes of vacuolating cytotoxin A (VacA) for nontoxic VacA vaccine against Helicobacter pylori (H pylori) infection.METHODS: Eleven VacA epitopes were predicted according to VacA antigenic bioinformatics. Three candidates of VacA epitope were constructed through different combined epitopes. The candidate was linked with E. coli heat-labile enterotoxin B (LTB) by a linker of 7 amino acids, and cloned into plasmid pQE-60 in which fusion LTB-VacA epitope was efficiently expressed. To test the antigencity of the candidate, 6 BALB/c mice were treated with the fusion LTB-VacA epitope through intraperitoneal injection. To explore the ability of inhibiting the toxicity of VacA, cantiserum against the candidate was used to counteract VacA that induced HeLa cells to produce cell vacuoles in vitro.RESULTS: Serum IgG against the candidate was induced in the BALB/c mice. In vitro, the three antisera against the candidate efficiently counteracted the toxicity of VacA, and decreased the number of cell vacuoles by 14.17%, 20.20%and 30.41% respectively.CONCLUSION: Two of the three candidates, LZ-VacA1and LZ-VacA2, can be used to further study the mechanism of vacuolating toxicity of VacA, and to construct nontoxic VacA vaccine against H pylori infection.

  19. Stability indicating method development and validation for simultaneous estimation of atorvastatin calcium and celecoxib in bulk and niosomal formulation by RP-HPLC

    Directory of Open Access Journals (Sweden)

    Priyanka S. Jadhav

    2015-09-01

    Full Text Available The present work describes development and validation of a specific, sensitive, precise and stability-indicating high-performance liquid chromatographic method of analysis of atorvastatin calcium and celecoxib, both as a bulk drug and in niosomal formulation. The analysis has been performed by using Cosmosil-C18 column (4.6 mm´250 mm, 5 m at 25 °C using acetonitrile: ammonium acetate buffer pH 5.0: methanol (50:25:25 v/v/v as mobile phase. The detection was carried out at 277nm with a flow rate of 1.0mL/min. The retention times of Atorvastatin calcium and Celecoxib were 6.195 and 3.989min, respectively. The method was validated according to ICH guidelines, for specificity, precision, linearity, accuracy and robustness. Atorvastatin calcium and Celecoxib were subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The degradation was observed in oxidation and acid hydrolysis. The linearity for atorvastatin calcium and celecoxib were in the range of 100-500 µg/mL. The recovery study of atorvastatin and celecoxib were found to be in the range of 98.96 - 99.92% and 98.90-100%, respectively. The proposed method was validated and successfully applied to the estimation of Atorvastatin calcium and Celecoxib in combined in-house niosomal formulation.

  20. Helicobacter pylori infection in pediatrics

    DEFF Research Database (Denmark)

    Wewer, Anne Vibeke; Kalach, Nicolas

    2003-01-01

    A high prevalence and early colonization of Helicobacter pylori infection in childhood was described again this year in developing countries in contrast to developed ones. Upper gastrointestinal endoscopy including gastric biopsies remains the diagnostic gold standard method for this infection...... in gastric manifestations is the subject of conflicting reports. Extra-digestive manifestations are also reported in the course of this infection. The treatment of H. pylori infection is influenced by resistance of the bacteria to the antibiotics used. We suggest that eradication of H. pylori should take...

  1. Selective cyclooxygenase-2 inhibitors show a differential ability to inhibit proliferation and induce apoptosis of colon adenocarcinoma cells.

    Science.gov (United States)

    Yamazaki, Ryuta; Kusunoki, Natsuko; Matsuzaki, Takeshi; Hashimoto, Shusuke; Kawai, Shinichi

    2002-11-01

    Although the influence of selective cyclooxygenase (COX)-2 inhibitors on the proliferation of colon adenocarcinoma cells have been the subject of much investigation, relatively little research has compared the effects of different COX-2 inhibitors. Celecoxib strongly suppressed the proliferation of COX-2 expressing HT-29 cells at 10-40 microM. NS-398 and nimesulide also inhibited cell proliferation, whereas rofecoxib, meloxicam, and etodolac did not. Only celecoxib induced apoptosis of HT-29 cells, as detected on the basis of DNA fragmentation, TUNEL positivity, and caspase-3/7 activation. DNA fragmentation was also increasd in COX-2 non-expressing cell lines (SW-480 and HCT-116) by exposure to celecoxib for 6-24 h. All six COX-2 inhibitors suppressed the production of prostaglandin E(2) by HT-29 cells, suggesting that the pro-apoptotic effect of celecoxib was unrelated to inhibition of COX-2. Inactivation of Akt might explain the differential pro-apoptotic effect of these selective COX-2 inhibitors on colon adenocarcinoma cells. PMID:12417326

  2. A STUDY OF COX-2 INHIBITOR CELECOXIB AND CHEMORADIATION IN PATIENTS WITH LOCALLY ADVANCED CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    Kuppa Prakash

    2016-08-01

    Full Text Available AIMS AND OBJECTIVES To evaluate efficacy of concurrent oral Cox-2 Inhibitor (celecoxib and chemoradiation in locoregional control, distant control, disease free survival and/or overall survival in patients with locally advanced cervical cancer. To determine treatment related toxicity rates in patients with locally advanced cervical cancer treated by oral celecoxib, intravenous cisplatin and concurrent pelvic radiation therapy. MATERIALS AND METHODS Study was done for a period of 2 years in a tertiary care cancer hospital which caters to the cancer patients. Advanced squamous, adenocarcinoma or adenosquamous carcinoma of uterine cervix, Patients with age <70 years, ECOG performance status 0-2, Normal haematological investigations, Normal renal function test, Normal liver function test, No disease outside of pelvis. RESULTS This prospective study consisted 30 patients, 15 patients on either arm. Overall pooled mean age for both study and comparison group was 50.3 years with a probability value P=0.91 for age. 14 patients (93.33% in both the arms had a performance status of ECOG 0 or 1 and 1 patient in both arms had ECOG PS-2. Stage distribution of the patients in study arm was 3 in IB2, 2 in IIA, 5 in IIB, 4 in III and 1 in stage IVA. In control arm, out of the 15 patients 2 are in IB2, 2 in IIA, 5 in IIB, 5 in III and 1 in stage IVA. The mean probability value was P=0.65 for stage distribution. 15 patients in arm-A (study arm received pelvic RT 50Gy 2Gy/Fr 5#/week followed by HDR –ICR 3 Fr. 700 cGy/Fr after pelvic RT on an average of 1 week along with weekly cisplatin 40 mg/m2 (50 mg (D1, D8, D15, D22 and Cox-2 inhibitor oral celecoxib 400 mg twice daily (800 mg/d starting from day 1 to throughout the duration of the chemoradiation. 15 patients in arm-B (Control arm received pelvic RT 50Gy 2Gy/Fr 5#/week followed by HDR –ICR 3 Fr. 700 cGy/Fr on an average of 1 week after pelvic RT along with weekly cisplatin 40 mg/m2 (50 mg (D1, D8, D15, D22

  3. Celecoxib Adjunctive Treatment to Antipsychotics in Schizophrenia: A Review of Randomized Clinical Add-On Trials

    Science.gov (United States)

    De Berardis, Domenico; Vellante, Federica; Santacroce, Rita; Orsolini, Laura; Valchera, Alessandro; Girinelli, Gabriella; Carano, Alessandro; Fornaro, Michele; Gambi, Francesco; Martinotti, Giovanni; Di Giannantonio, Massimo

    2016-01-01

    Schizophrenia is a severe, chronic and debilitating mental disorder. Past literature has reported various hypotheses about the psychopathology of schizophrenia. Recently, a growing literature has been trying to explain the role of inflammation in the etiopathogenesis of schizophrenia. In the past, numerous immune modulation and anti-inflammatory treatment options have been proposed for schizophrenia, but sometimes the results were inconsistent. Electronic search was carried out in November 2015. PubMed and Scopus databases have been used to find studies to introduce in this review. Only randomized-placebo-controlled add-on trials were taken into account. In this way, six articles were obtained for the discussion. Celecoxib showed beneficial effects mostly in early stages of schizophrenia. In chronic schizophrenia, the data are controversial, possibly in part for methodological reasons. PMID:27524864

  4. Response surface methodology for the optimization of celecoxib self-microemulsifying drug delivery system

    Directory of Open Access Journals (Sweden)

    Shaji Jessy

    2008-01-01

    Full Text Available The aim of the present study was to prepare, evaluate and optimize, self micro emulsifying drug delivery system of celecoxib. A 3 factor, 3 level factorial design was used for the optimization procedure with different amounts of Labrafil 2609 WL, Labrasol, and Cremophor EL as the independent variables. The response variable was selected on particle size (nm of the droplets after dilution in 0.1N HCl. Particle size of the self micro-emulsifying drug delivery system depends on the quantity of above three independent variables. Three different levels of each independent variable were selected for the optimization. Mathematical equation and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the particle size after dilution was, Particle size (Y= +27.83+76.07xA-23.62xB-43.83xC+52.72xA2+9.82xB2+27.20xC2-14.52xAxB-32.38xAxC+12.1xBxC, where, A=Labrafil 2609 WL, B= Labrasol, C= Cremophor EL, Y= particle size. The optimized model predicted a particle size of 28.33 nm with 0.16ml of labrafil 2609 WL, 0.17ml Labrasol and 0.22 ml of Cremophor EL.The observed response were in close agreement with the predicted values of the optimized formulation. This demonstrates the reliability of the optimization procedure in predicting particle size of self microemulsifying delivery system for celecoxib.

  5. Neoadjuvant chemoradiation with capcitabine and celecoxib in stage II and III rectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Aghili M

    2010-10-01

    Full Text Available "nBackground: Colorectal cancer is the third common cancer world wide and the forth in Iran. Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer. In this study we evaluate the efficacy a cox-2 inhibitor on pathologic response, sphincter preservation and acute toxicity during neoadjuvant chemoradiation."n "nMethods: Thirty-six patients that have adenocarcinoma of rectum was enrolled (up to 15 cm of anal verge. The patients were undergone Endometrial Ultrasound (EUS, abdomino-pelvic and chest CT for staging. Then received neoadjuvant concurrent chemo radiation (xeloda 825 mg/m2 bid in combination with celecoxib 100 mg qid and 50-50.4Gy/25-28f. Surgery was done 4-8 weeks after chemoradiation. During the chemoradiation the patients was observed for the probable complication one year. Tumor regression grade was reported."n "nResults: From 36 surgery patients, Total Mesorectal Excision (TME was done in 30 patients. Pathologic complete response was seen in eight of 30 patients (26.7%. Tumor regression grade was calculated in three and five grade system: in three grade system 17 patients had grade 1 (60.7%, eight patients had grade 2 (28.6% and three patients had grade 3 (10.7%. In five grade system of tumor regression eight patients had grade 1 (28.6%, nine patients had grade 2 (32.1%, eight patients grade 3 (28.6%, three patients had grade 4 (10.7%. T down staging was 43.3%. N downstaging was 30.8%. No patient had skin reaction or cardio-vascular complication."n "nConclusion: Based on our study results, Celecoxib in combination with neoadjuvant chemoradiation is safe and is associated with low complications. This combination can promote pathologic complete response, TRG and T and N downstaging in Rectal adenocarcinoma.

  6. Cardiovascular safety of celecoxib in acute myocardial infarction patients: a nested case-control study

    Directory of Open Access Journals (Sweden)

    Josiane Courteau

    2009-04-01

    Full Text Available The objective was to measure the impact of exposure to coxibs and non-steroidal anti-inflammatory drugs (NSAID on morbidity and mortality in older patients with acute myocardial infarction (AMI. A nested case-control study was carried out using an exhaustive population-based cohort of patients aged 66 years and older living in Quebec (Canada who survived a hospitalization for AMI (ICD-9 410 between 1999 and 2002. The main variables were all-cause and cardiovascular (CV death, subsequent hospital admission for AMI, and a composite end-point including recurrent AMI or CV death. Conditional logistic regressions were used to estimate the risk of mortality and morbidity. A total of 19,823 patients aged 66 years and older survived hospitalization for AMI in the province of Quebec between 1999 and 2002. After controlling for covariables, the risk of subsequent AMI and the risk of composite end-point were increased by the use of rofecoxib. The risk of subsequent AMI was particularly high for new rofecoxib users (HR 2.47, 95% CI 1.57-3.89. No increased risk was observed for celecoxib users. No increased risk of CV death was observed for patients exposed to coxibs or NSAIDs. Patients newly exposed to NSAIDs were at an increased risk of death (HR 2.22, 95% CI 1.30-3.77 and of composite end-point (HR 2.28, 95% CI 1.35-3.84. Users of rofecoxib and NSAIDs, but not celecoxib, were at an increased risk of recurrent AMI and of composite end-point. Surprisingly, no increased risk of CV death was observed. Further studies are needed to better understand these apparently contradictory results.

  7. Helicobacter Infection and Chronic Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Zhao-chun Chi; Xin-juan Yu; Quan-jiang Dong

    2014-01-01

    This paper reviews the recentHelicobacter infection associated with chronic liver disease. The bacteriology, prevalence, pathogenesis and diagnosis were reviewed. Future work should be conducted on the pathogenesis and treatment of this disease.

  8. Helicobacter pylori Infection in Pediatrics.

    Science.gov (United States)

    Roma, Eleftheria; Miele, Erasmo

    2015-09-01

    This review includes the main pediatric studies published from April 2014 to March 2015. The host response of Treg cells with increases in FOXP3 and TGF-β1 combined with a reduction in IFN-γ by Teff cells may contribute to Helicobacter pylori susceptibility in children. Genotypic variability in H. pylori strains influences the clinical manifestation of the infection. Helicobacter pylori infection is associated with variables indicative of a crowded environment and poor living conditions, while breast-feeding has a protective effect. Intrafamilial infection, especially from mother to children and from sibling to sibling, is the dominant transmission route. Studies showed conflicting results regarding the association between H. pylori infection and iron deficiency anemia. One study suggests that H. pylori eradication plays a role in the management of chronic immune thrombocytopenic purpura in H. pylori-infected children and adolescents. The prevalence of H. pylori was higher in chronic urticaria patients than in controls and, following H. pylori eradication, urticarial symptoms disappeared. An inverse relationship between H. pylori infection and allergic disease was reported. Antibiotic resistance and insufficient compliance to treatment limit the efficacy of eradication therapy. Sequential therapy had no advantage over standard triple therapy. In countries where H. pylori infection is prevalent, studies focusing on virulence factors and antibiotic susceptibility may provide anticipation of the prognosis and may be helpful to reduce morbidity and mortality.

  9. Helicobacter pylori: Beginning the Second Decade

    OpenAIRE

    Matisko, Ann; Thomson, ABR

    1995-01-01

    ‘Beginning the Second Decade’ - a recent international meeting on Helicobacter pylori - was held in conjunction with the VIIth International Workshop on Gastroduodenal Pathology and H pylori and with the meeting of the European Helicobacter pylori Study Group in Houston, Texas from September 30 to October 1, 1994. A menu of 476 abstracts, published in the American Journal of Gastroenterology (1994;89:8), highlighted the explosion of advances in this area. The Houston meeting was followed by t...

  10. Critical solvent properties affecting the particle formation process and characteristics of celecoxib-loaded PLGA microparticles via spray-drying

    DEFF Research Database (Denmark)

    Wan, Feng; Bohr, Adam; Maltesen, Morten Jonas;

    2013-01-01

    power of the feed solution. An obvious burst release was observed for the microparticles prepared by the feed solutions with the highest amount of poor solvent for PLGA. TGA analysis revealed distinct drying kinetics for the binary mixtures. CONCLUSIONS: The particle formation process is mainly governed......) microparticles prepared by spray-drying. METHODS: Binary mixtures of acetone and methanol at different molar ratios were applied to dissolve celecoxib and PLGA prior to spray-drying. The resulting microparticles were characterized with respect to morphology, texture, surface chemistry, solid state properties...... by the PLGA precipitation rate, which is solvent-dependent, and the migration rate of celecoxib molecules during drying. The texture and surface chemistry of the spray-dried PLGA microparticles can therefore be tailored by adjusting the solvent composition....

  11. Antiadhesive Properties of Arabinogalactan Protein from Ribes nigrum Seeds against Bacterial Adhesion of Helicobacter pylori

    OpenAIRE

    Jutta Messing; Michael Niehues; Anna Shevtsova; Thomas Borén; Andreas Hensel

    2014-01-01

    Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with beta-glucosyl Yariv. Functional testing of F2 was performed by semiquantitative in situ...

  12. Antiadhesive Properties of Abelmoschus esculentus (Okra) Immature Fruit Extract against Helicobacter pylori Adhesion

    OpenAIRE

    Messing, Jutta; Thoele, Christian; Niehues, Michael; Shevtsova, Anna; Glocker, Erik; Boren, Thomas; Hensel, Andreas

    2014-01-01

    Background: Traditional Asian and African medicine use immature okra fruits (Abelmoschus esculentus) as mucilaginous food to combat gastritis. Its effectiveness is due to polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach tissue. The present study investigates the antiadhesive effect in mechanistic detail. Methodology: A standardized aqueous fresh extract (Okra FE) from immature okra fruits was used for a quantitative in vitro adhesion assay with FITC-labled H. pylori...

  13. A comparative study between the efficacy of tramadol, celecoxib and ibuprofen in pain control after root canal therapy of tooth

    Directory of Open Access Journals (Sweden)

    Eshagh A. Saberi

    2011-01-01

    Full Text Available Background: Root canal therapy of teeth can relief the endodontic pain, but post-endodontic pain and discomfort are its undesirable effects. There are many studies on various drugs for alleviation of post-endodontic pain. The aim of this study was to compare the analgesic effect of tramadol, celecoxib and ibuprofen in vital teeth.Materials & Method: In this double blind randomized clinical trial study, 104 patients with vital first mandibular molar tooth were selected. The patients were divided in to four groups, tramadol (A, celecoxib (B, ibuprofen (C and placebo (D. The similar capsules were filled with50mg tramadol HCL, 100mg celecoxib, 400mg ibuprofen and starch . Each patient received randomly one capsule one hour before treatment. If the pain persists, the patient received one tablet of 325 mg acetaminophen every 6 hours. The groups were controlled for 3 days. The data were collected one hour before and 6, 12, 24, 48, 72 hours after treatment. Results were analyzed using kruskal-wallis and Mann-Whitney U tests.Results: The results showed that after 12 (p=0.039 and 24(p=0.024 hours of treatment, tramadol was better in pain relief in comparison with other groups and there was one difference between tramadol and ibuprofen after treatment after 12 hours (p=0.013. But there was no significant deference between drug groups at 6, 48 and 72 hour after treatment.Conclusion: Tramadol prescription in comparison with celecoxib, ibuprofen and placebo has greater analgesic effect after root canal therapy in vital teeth. In addition tramadol may be a good medicine for post-endodontic pain control

  14. A comparative study between the efficacy of tramadol, celecoxib and ibuprofen in pain control after root canal therapy of tooth

    OpenAIRE

    Eshagh A Saberi; S. Mohsen Hosseini-Goosheh; Roohollah Mirkahnooj; Hossein Ansari

    2011-01-01

    Background: Root canal therapy of teeth can relief the endodontic pain, but post-endodontic pain and discomfort are its undesirable effects. There are many studies on various drugs for alleviation of post-endodontic pain. The aim of this study was to compare the analgesic effect of tramadol, celecoxib and ibuprofen in vital teeth.Materials & Method: In this double blind randomized clinical trial study, 104 patients with vital first mandibular molar tooth were selected. The patients were divid...

  15. The tell-tale heart: population-based surveillance reveals an association of rofecoxib and celecoxib with myocardial infarction.

    Directory of Open Access Journals (Sweden)

    John S Brownstein

    Full Text Available BACKGROUND: COX-2 selective inhibitors are associated with myocardial infarction (MI. We sought to determine whether population health monitoring would have revealed the effect of COX-2 inhibitors on population-level patterns of MI. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective study of inpatients at two Boston hospitals, from January 1997 to March 2006. There was a population-level rise in the rate of MI that reached 52.0 MI-related hospitalizations per 100,000 (a two standard deviation exceedence in January of 2000, eight months after the introduction of rofecoxib and one year after celecoxib. The exceedence vanished within one month of the withdrawal of rofecoxib. Trends in inpatient stay due to MI were tightly coupled to the rise and fall of prescriptions of COX-2 inhibitors, with an 18.5% increase in inpatient stays for MI when both rofecoxib and celecoxib were on the market (P<0.001. For every million prescriptions of rofecoxib and celecoxib, there was a 0.5% increase in MI (95%CI 0.1 to 0.9 explaining 50.3% of the deviance in yearly variation of MI-related hospitalizations. There was a negative association between mean age at MI and volume of prescriptions for celecoxib and rofecoxib (Spearman correlation, -0.67, P<0.05. CONCLUSIONS/SIGNIFICANCE: The strong relationship between prescribing and outcome time series supports a population-level impact of COX-2 inhibitors on MI incidence. Further, mean age at MI appears to have been lowered by use of these medications. Use of a population monitoring approach as an adjunct to pharmacovigilence methods might have helped confirm the suspected association, providing earlier support for the market withdrawal of rofecoxib.

  16. Design and baseline characteristics of participants in a phase III randomized trial of celecoxib and selenium for colorectal adenoma prevention

    OpenAIRE

    Thompson, Patricia; Roe, Denise J.; Fales, Liane; Buckmeier, Julie; Wang, Fang; Hamilton, Stanley R.; Bhattacharyya, Achyut; Green, Sylvan; Hsu, Chiu-Hsieh; Chow, H-H Sherry; Ahnen, Dennis J.; Boland, C Richard; Russell I. Heigh; Fay, David E.; Martinez, Maria Elena

    2012-01-01

    Cyclooxygenase (COX) inhibitors reduce colorectal adenoma recurrence by up to 45% and selenium supplementation may prevent colorectal cancer. Following colonoscopic adenoma resection, 1,600 men and women aged 40-80 years were randomized to celecoxib (400 mg daily), a selective COX-2 inhibitor, and/or selenium (200 μg daily as selenized yeast), or double placebo. The trial was initiated in November, 2001. The primary trial endpoint is adenoma recurrence in each intervention group compared to p...

  17. Helicobacter infection in hepatocellular carcinoma tissue

    Institute of Scientific and Technical Information of China (English)

    Shi-Ying Xuan; Ning Li; Xin Qiang; Rong-Rong Zhou; Yong-Xin Shi; Wen-Jie Jiang

    2006-01-01

    AIM: To investigate whether Helicobacter species (Helicobacter spp.) could be detected in hepatocellular carcinoma (HCC) tissue.METHODS: Liver samples from 28 patients with hepatocellular carcinoma (HCC) diagnosed by histopathology were studied. Twenty-two patients with other liver diseases (5 with liver trauma, 7 with cavernous liver hemangioma, 6 with liver cyst and 4 with hepatolithiasis), 25 patients with gastric cancer, 15 with colonic cancer and 15 with myoma of uterus served as controls. Two piceces of biopsy were obtained from each patient. One was cultured for Helicobacter spp. and extraction of DNA, the other was prepared for scanning electron microscopy (SEM) and in situ hybridization. The samples were cultured on Columbia agar plates with microaerobic techniques. Helicobacter spp. in biopsy from the studied subjects was detected by polymerase chain reaction (PCR) with Helicobacter spp. 16S rRNA primers. Amplified products were identified by Southern hybridization and sequenced further. Besides, other genes (vacA, cagA) specific for Helicobacter pylori (H pylori) were also detected by PCR. Helicobacter spp. in biopsies was observed by SEM. Transmission electron microscopy (TEM) was performed to identify the cultured positive Helicobacter spp. The presence of Helicobacter spp. was detected by in situ hybridization to confirm the type of Helicobacter.RESULTS: The positive rate of Helicobacter cultured in HCC and gastric cancer tissue was 10.7% (3/28) and 24%(6/25), respectively. Helicobacter microorganisms were identified further by typical appearance on Gram staining, positive urease test and characteristic colony morphology on TEM. The bacterium was observed in adjacent hepatocytes of the two HCC samples by SEM.The number of cocci was greater than that of bacilli. The bacterium was also found in four gastric cancer samples.PCR showed that the positive rate of HCC and gastric cancer samples was 60.7% and 72% respectively, while the controls were negative

  18. Calcium Alginate and Calcium Alginate-Chitosan Beads Containing Celecoxib Solubilized in a Self-Emulsifying Phase

    Directory of Open Access Journals (Sweden)

    Lorena Segale

    2016-01-01

    Full Text Available In this work alginate and alginate-chitosan beads containing celecoxib solubilized into a self-emulsifying phase were developed in order to obtain a drug delivery system for oral administration, able to delay the drug release in acidic environment and to promote it in the intestinal compartment. The rationale of this work was linked to the desire to improve celecoxib therapeutic effectiveness reducing its gastric adverse effects and to favor its use in the prophylaxis of colon cancer and as adjuvant in the therapy of familial polyposis. The systems were prepared by ionotropic gelation using needles with different diameters (400 and 600 μm. Morphology, particle size, swelling behavior, and in vitro drug release performance of the beads in aqueous media with different pH were investigated. The experimental results demonstrated that the presence of chitosan in the formulation caused an increase of the mechanical resistance of the bead structure and, as a consequence, a limitation of the bead swelling ability and a decrease of the drug release rate at neutral pH. Alginate-chitosan beads could be a good tool to guarantee a celecoxib colon delivery.

  19. Calcium Alginate and Calcium Alginate-Chitosan Beads Containing Celecoxib Solubilized in a Self-Emulsifying Phase.

    Science.gov (United States)

    Segale, Lorena; Giovannelli, Lorella; Mannina, Paolo; Pattarino, Franco

    2016-01-01

    In this work alginate and alginate-chitosan beads containing celecoxib solubilized into a self-emulsifying phase were developed in order to obtain a drug delivery system for oral administration, able to delay the drug release in acidic environment and to promote it in the intestinal compartment. The rationale of this work was linked to the desire to improve celecoxib therapeutic effectiveness reducing its gastric adverse effects and to favor its use in the prophylaxis of colon cancer and as adjuvant in the therapy of familial polyposis. The systems were prepared by ionotropic gelation using needles with different diameters (400 and 600 μm). Morphology, particle size, swelling behavior, and in vitro drug release performance of the beads in aqueous media with different pH were investigated. The experimental results demonstrated that the presence of chitosan in the formulation caused an increase of the mechanical resistance of the bead structure and, as a consequence, a limitation of the bead swelling ability and a decrease of the drug release rate at neutral pH. Alginate-chitosan beads could be a good tool to guarantee a celecoxib colon delivery. PMID:27127680

  20. The effect of Helicobacter pylori on asthma and allergy

    Directory of Open Access Journals (Sweden)

    Amedeo Amedei

    2010-09-01

    Full Text Available Amedeo Amedei1, Gaia Codolo2, Gianfranco Del Prete1, Marina de Bernard2, Mario M D’Elios11Policlinico AOU Careggi, Department Internal Medicine, University of Florence, Italy; 2Venetian Institute of Molecular Medicine, University of Padua, ItalyAbstract: Current evidence indicates an inverse association between Helicobacter pylori and asthma and allergy. H. pylori is a Gram-negative bacterium which represents the major cause of peptic ulcer and gastric cancer, and preferentially elicits a T helper (Th-1 response. Many H. pylori factors, such as the neutrophil-activating factor of H. pylori (HP-NAP, are able to drive Th-1 polarization and to display a powerful inhibition of allergic Th-2 response. This article proposes an overview of the actual knowledge about the effects of H. pylori on asthma and allergy. Special attention has been drawn to HP-NAP as a potential novel strategy for the prevention and treatment of asthma and atopy.Keywords: Helicobacter pylori neutrophil-activating factor, protein, Th-1/Th-2, Treg, asthma

  1. [Helicobacter pylori infection in childhood].

    Science.gov (United States)

    Okuda, Masumi; Fukuda, Yoshihiro

    2009-12-01

    Helicobacter pylori (H. pylori) infection is mainly acquired in the first 2 or 3 years and the risk of infection declines rapidly after 5 years of age. In developing countries, acquisition age of the infection is probably lower than in developed countries. In Japan, main transmission route is intrafamilial and mother to children infection is most important. But in developing countries, some reports suggest that extrafamilial infection is more important. The famous paper revealed that H. pylori can be cultivated from vomitus, saliva and cathartic stools and the possibility of source of H. pylori infection. Bed sharing, large number of family members, delayed weaning from a feeding bottle, regurgitated gastric juice in the mother's mouth are reported as risk factors of the infection. PMID:19999106

  2. Eradication of Helicobacter pylori Infection.

    Science.gov (United States)

    Marcus, Elizabeth A; Sachs, George; Scott, David R

    2016-07-01

    Helicobacter pylori infects about 50 % of the world's population, causing at a minimum chronic gastritis. A subset of infected patients will ultimately develop gastric or duodenal ulcer disease, gastric adenocarcinoma, or MALT (mucosa-associated lymphoid tissue) lymphoma. Eradication of H. pylori requires complex regimens that include acid suppression and multiple antibiotics. The efficacy of treatment using what were once considered standard regimens have declined in recent years, mainly due to widespread development of antibiotic resistance. Addition of bismuth to standard triple therapy regimens, use of alternate antibiotics, or development of alternative regimens using known therapies in novel combinations have improved treatment efficacy in specific populations, but overall success of eradication remains less than ideal. Novel regimens under investigation either in vivo or in vitro, involving increased acid suppression ideally with fewer antibiotics or development of non-antibiotic treatment targets, show promise for future therapy. PMID:27177639

  3. Helicobacter pylori and nonmalignant diseases.

    LENUS (Irish Health Repository)

    Alakkari, Alaa

    2012-02-01

    Research published over the past year has documented the continued decline of Helicobacter pylori-related peptic ulcer disease and increased recognition of non-H. pylori, non-steroidal anti-inflammatory drugs ulcer disease--idiopathic ulcers. Despite reduced prevalence of uncomplicated PUD, rates of ulcer complications and associated mortality remain stubbornly high. The role of H. pylori in functional dyspepsia is unclear, with some authors considering H. pylori-associated nonulcer dyspepsia a distinct organic entity. There is increasing acceptance of an inverse relationship between H. pylori and gastroesophageal reflux disease (GERD), but little understanding of how GERD might be more common\\/severe in H. pylori-negative subjects. Research has focused on factors such as different H. pylori phenotypes, weight gain after H. pylori eradication, and effects on hormones such as ghrelin that control appetite.

  4. Análisis coste-efectividad del empleo de celecoxib en el tratamiento de la artrosis

    Directory of Open Access Journals (Sweden)

    Moreno A.

    2003-01-01

    Full Text Available Antecedentes: Los antiinflamatorios no esteroideos (AINE, utilizados en el tratamiento de la artrosis, pueden producir reacciones adversas gastrointestinales (GI graves. Celecoxib, un inhibidor específico de la ciclooxigenasa 2 (COX-2, ha demostrado una eficacia equivalente a los AINE convencionales con un mejor perfil de tolerabilidad y seguridad. Objetivo: La finalidad de este estudio ha sido realizar un análisis coste-efectividad sobre el uso de celecoxib frente a los AINE clásicos en el tratamiento de la artrosis. Material y métodos: El análisis coste-efectividad se ha diseñado mediante un modelo farmacoeconómico, definiéndose como unidad de efectividad a cada año de vida ganado tras la toma de celecoxib o AINE. La probabilidad de que aparezcan los diferentes resultados clínicos se ha obtenido de artículos publicados y de asunciones incorporadas. Sólo se han valorado los costes directos médicos (medicación, hospitalización, pruebas complementarias, analíticas, visitas extras, etc., sin haberse incluido otros costes. La perspectiva del estudio ha sido la del Sistema Nacional de Salud y el horizonte temporal elegido ha sido de 6 meses. Resultados: El coste adicional por cada año de vida ganado secundario al uso de celecoxib frente a los AINE clásicos asciende a 8.017 ? (1.333.834 ptas.. El análisis de sensibilidad muestra cómo estos valores son sensibles a la modificación del coste de AINE y gastroprotector, así como a la inclusión de grupos poblacionales con edades más bajas. Conclusiones: Celecoxib puede ser considerado como una opción coste-efectiva en el tratamiento de la artrosis, ya que va a evitar muertes y a ganar años de vida para los pacientes con un coste adicional razonable y moderado, cuando se compara con los AINE. Su eficiencia aumenta a medida que se utiliza en poblaciones con menor edad media y, probablemente, en aquellas con mayor riesgo de desarrollar complicaciones GI.

  5. Celecoxib offsets the negative renal influences of cyclosporine via modulation of the TGF-β1/IL-2/COX-2/endothelin ET{sub B} receptor cascade

    Energy Technology Data Exchange (ETDEWEB)

    El-Gowelli, Hanan M. [Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria (Egypt); Helmy, Maged W.; Ali, Rabab M. [Pharmacology and Toxicology, Faculty of Pharmacy, Pharos University, Alexandria (Egypt); El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com [Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria (Egypt)

    2014-03-01

    Endothelin (ET) signaling provokes nephrotoxicity induced by the immunosuppressant drug cyclosporine A (CSA). We tested the hypotheses that (i): celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, counterbalances renal derangements caused by CSA in rats and (ii) the COX-2/endothelin ET{sub B} receptor signaling mediates the CSA-celecoxib interaction. Ten-day treatment with CSA (20 mg/kg/day) significantly increased biochemical indices of renal function (serum urea, creatinine), inflammation (interleukin-2, IL-2) and fibrosis (transforming growth factor-β{sub 1}, TGF-β{sub 1}). Histologically, CSA caused renal tubular atrophy along with interstitial fibrosis. These detrimental renal effects of CSA were largely reduced in rats treated concurrently with celecoxib (10 mg/kg/day). We also report that cortical glomerular and medullary tubular protein expressions of COX-2 and ET{sub B} receptors were reduced by CSA and restored to near-control values in rats treated simultaneously with celecoxib. The importance of ET{sub B} receptors in renal control and in the CSA-celecoxib interaction was further verified by the findings (i) most of the adverse biochemical, inflammatory, and histopathological profiles of CSA were replicated in rats treated with the endothelin ET{sub B} receptor antagonist BQ788 (0.1 mg/kg/day, 10 days), and (ii) the BQ788 effects, like those of CSA, were alleviated in rats treated concurrently with celecoxib. Together, the data suggest that the facilitation of the interplay between the TGF-β1/IL-2/COX-2 pathway and the endothelin ET{sub B} receptors constitutes the cellular mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in rats. - Highlights: • Celecoxib abolishes nephrotoxic manifestations of CSA in rats. • Blockade of ETB receptors by BQ788 mimicked the nephrotoxic effects of CSA. • CSA or BQ788 reduces renal protein expression of COX-2 and endothelin ETB receptors. • Enhanced TGFβ1/IL-2/COX2/ETB

  6. Análisis coste-efectividad del empleo de celecoxib en el tratamiento de la artrosis Cost-effectiveness analysis of the use of celecoxib for the treatment of osteoarthritis

    Directory of Open Access Journals (Sweden)

    A. Moreno

    2003-02-01

    Full Text Available Antecedentes: Los antiinflamatorios no esteroideos (AINE, utilizados en el tratamiento de la artrosis, pueden producir reacciones adversas gastrointestinales (GI graves. Celecoxib, un inhibidor específico de la ciclooxigenasa 2 (COX-2, ha demostrado una eficacia equivalente a los AINE convencionales con un mejor perfil de tolerabilidad y seguridad. Objetivo: La finalidad de este estudio ha sido realizar un análisis coste-efectividad sobre el uso de celecoxib frente a los AINE clásicos en el tratamiento de la artrosis. Material y métodos: El análisis coste-efectividad se ha diseñado mediante un modelo farmacoeconómico, definiéndose como unidad de efectividad a cada año de vida ganado tras la toma de celecoxib o AINE. La probabilidad de que aparezcan los diferentes resultados clínicos se ha obtenido de artículos publicados y de asunciones incorporadas. Sólo se han valorado los costes directos médicos (medicación, hospitalización, pruebas complementarias, analíticas, visitas extras, etc., sin haberse incluido otros costes. La perspectiva del estudio ha sido la del Sistema Nacional de Salud y el horizonte temporal elegido ha sido de 6 meses. Resultados: El coste adicional por cada año de vida ganado secundario al uso de celecoxib frente a los AINE clásicos asciende a 8.017 € (1.333.834 ptas.. El análisis de sensibilidad muestra cómo estos valores son sensibles a la modificación del coste de AINE y gastroprotector, así como a la inclusión de grupos poblacionales con edades más bajas. Conclusiones: Celecoxib puede ser considerado como una opción coste-efectiva en el tratamiento de la artrosis, ya que va a evitar muertes y a ganar años de vida para los pacientes con un coste adicional razonable y moderado, cuando se compara con los AINE. Su eficiencia aumenta a medida que se utiliza en poblaciones con menor edad media y, probablemente, en aquellas con mayor riesgo de desarrollar complicaciones GI.Background: Non

  7. Successful culture techniques for Helicobacter species: general culture techniques for Helicobacter pylori.

    Science.gov (United States)

    Whitmire, Jeannette M; Merrell, D Scott

    2012-01-01

    Half of the world's population is persistently infected with Helicobacter pylori. The chronicity of this infection ultimately elicits clinical manifestations ranging from gastritis and peptic ulcers to adenocarcinoma and MALT lymphoma. Laboratory research following the initial observations of Helicobacter species was greatly hindered by an inability to isolate and culture the bacteria. Thus, the ability to culture bacterial species from this genus is an extremely important step in expanding clinical knowledge and development of therapies. This chapter describes successful techniques for culturing H. pylori on selective horse blood agar media and in Brucella broth liquid media. Additionally, the specific growth requirements of other Helicobacter species are noted.

  8. 塞来昔布联合紫杉醇对人乳腺癌MCF-7/Taxol耐药细胞株多药耐药的逆转作用及机制的探讨%Effect of Combination of Taxol and Celecoxib on Reversing Multidrug Resistance Human Breast Cancer Cells (MCF-7/ Taxol) and Explore Its Underlying Mechanism

    Institute of Scientific and Technical Information of China (English)

    柳青; 刘雪娟; 陈玉娟; 汪静

    2011-01-01

    Objective To investigate the reversal effect of Celecoxib and Taxol on multidrug resistance (MDR) human breast cancer cells (MCF-7/Taxol) and its underlying mechanism.Methods After establishing the resistance cell lines of human breast cancer on Taxol (MCF-7/Taxol), the effects of the drugs on the toxicity of MCF-7/Taxol cells and the reversal effect of Celecoxib on MDR were determined by CCK-8 assay.The cells were divided into seven groups (A: MCF-7; B: MCF-7/Taxol; C: MCF-7/Taxol+ 0.03 μg/mL Taxol; D: MCF-7/Taxol+0.03 μg/mL Taxol+3 μg/mL Celecoxib; E: MCF-7/Taxol+0.03 μg/mL Taxoll6 μg/mL Celecoxib; F:MCF-7/Taxol+3 μg/mL Celecoxib; G: MCF-7/Taxol +6 μg/mL Celecoxib).The mRNA levels of MDR1 and BCRP in these treated cells were also determined by reverse transcription-polymerase chain reaction (RT-PCR), the protein levels of P-gp and BCRP in these treated cells were also determined by Western blot method.Results Compared with the Taxol control, the cytotoxicity effects was obviously increased by combination of Taxol and Celecoxib (P<0.05).Compared with the vehicle control, Taxol up-regulated mRNA and protein levels of P-gp,whereas Celecoxib down-regulated mRNA and protein levels of P-gp and BCRP (P<0.05).Conclusion Celecoxib has reversal effect on MDR in MCF-7/Taxol cells, it's possible mechanism might be related to reduce the protein expression of COX-2, the inhibition of P-gp, BCRP mRNA and protein overexpression.%目的 观察环氧化酶-2(COX-2)选择性抑制剂塞来昔布(Celecoxib)联合紫杉醇(Taxol)对人乳腺癌MCF-7/Taxol耐药细胞多药耐药(multiple drug resistance,MDR)的逆转作用,并初步探讨其作用机制.方法 体外诱导建立人乳腺癌MCF-7/Taxol耐药细胞株,CCK-8法检测Taxol、塞来昔布对MCF-7/Taxol细胞的毒性作用及塞来昔布对MCF-7/Taxol细胞多药耐药的逆转作用.实验分为:同步传代的MCF-7细胞组(A组),MCF-7/Taxol细胞阴性对照组(B组),单用Taxol无毒剂量的MCF-7/Taxol细

  9. Characterization of the respiratory chain of Helicobacter pylori

    DEFF Research Database (Denmark)

    Chen, M; Andersen, L P; Zhai, L;

    1999-01-01

    The respiratory chain of Helicobacter pylori has been investigated. The total insensitivity of activities of NADH dehydrogenase to rotenone and of NADH-cytochrome c reductase to antimycin is indicative of the absence of the classical complex I of the electron transfer chain in this bacterium. NADPH......-dependent respiration was significantly stronger than NADH-dependent respiration, indicating that this is a major respiratory electron donor in H. pylori. Fumarate and malonate exhibited a concentration-dependent inhibitory effect on the activity of succinate dehydrogenase. The activity of succinate-cytochrome c...... reductase was inhibited by antimycin, implying the presence of a classical pathway from complex II to complex III in this bacterium. The presence of NADH-fumarate reductase (FRD) was demonstrated in H. pylori and fumarate could reduce H2O2 production from NADH, indicating fumarate to be an endogenous...

  10. Treatment of children with Helicobacter pylori infection and malabsorption syndromes with probiotics: Comparison with conventional methods

    International Nuclear Information System (INIS)

    It is stated that in developing countries a high rate of Helicobacter pylori infection among newborns and young children occurs. It is further assumed that this incidence may lead to inhibition of defense mechanism (inhibition of acid secretion) against bacteria, per orally ingested. This may result in excessive colonisation of the small intestine by bacteria. This situation may become a major cause for chronic malnutrition and diarrhoea syndrome with failure to thrive. This project aims at determining the occurrence of Helicobacter pylori infection in children at young age. It is aimed also at tracing the relationship between the Helicobacter pylori infection and the state of undernourishment. Finally it is aimed at comparing the usefulness of pre-/probiotics as anti-infection treatment. The methods used to demonstrate above mentioned parameters are based on stable isotopes, 13CO2 and H2 breath tests mainly. To assess nutritional status and progress in growth conventional anthropometric techniques will be used, complementary to the results obtained by stable isotopes. It is put forward that the use of pre-/probiotics, instead of antibiotics, will suppress upper gastrointestinal infection and restore the intestinal cell capacity to assimilate all food ingredients. (author)

  11. Inulin based micelles loaded with curcumin or celecoxib with effective anti-angiogenic activity.

    Science.gov (United States)

    Mandracchia, Delia; Tripodo, Giuseppe; Trapani, Adriana; Ruggieri, Simona; Annese, Tiziana; Chlapanidas, Theodora; Trapani, Giuseppe; Ribatti, Domenico

    2016-10-10

    Curcumin (CUR) and celecoxib (CLX) are two highly hydrophobic drugs which show bioavailability problems due to their poor aqueous solubility. The aim of this study was to encapsulate each of these drugs in micelles based on biodegradable and amphiphilic polymers to investigate their anti-angiogenesis activity. Here we use an amphiphilic polymer, based on two natural substances from renewable resources (Inulin and Vitamin E, INVITE), as a self-assembling system for the drug delivery of CUR and CLX. By the in vivo assay of chick embryo chorioallantoic membrane (CAM) it was assessed that both INVITE-CUR and INVITE-CLX micelles possess remarkable anti-angiogenic activity, while the INVITE micelles alone resulted intrinsically pro-angiogenic. Furthermore, it has been shown that encapsulation of CUR and CLX in INVITE micelles enhances of several magnitudes the water-solubility of CUR and CLX (14·10(5) and 3·10(2) times for CUR and CLX, respectively). These results may have interesting implications not only in anticancer or diabetic maculopathy therapy based on the anti-angiogenesis strategy but also for regenerative medicine where over-production of new vessels is required.

  12. Lenalidomide, celecoxib, and azacitidine therapy for blastic plasmocytoid dendritic cell neoplasm: a case report.

    Science.gov (United States)

    Garcia-Recio, Marta; Martinez-Serra, Jordi; Bento, Leyre; Ramos, Rafael; Gines, Jordi; Daumal, Jaime; Sampol, Antonia; Gutierrez, Antonio

    2016-01-01

    Blastic plasmocytoid dendritic cell neoplasm is characterized by aggressive behavior with a tendency for systemic dissemination and a predilection for skin, lymph nodes, soft tissues, peripheral blood, or bone marrow. It usually occurs in elderly patients with a mean age between 60 and 70 years. Despite initial response to chemotherapy, the disease regularly relapses with a short median overall survival. Better outcomes have been reported with high-dose acute leukemia-like induction chemotherapy followed by consolidation with allogeneic hematopoietic stem cell transplantation. However, elderly patients are not candidates for intensive therapy or allogeneic stem cell transplantation. So, new active and tolerable drugs are needed. Our case illustrates that one cycle of lenalidomide and celecoxib provides at least a partial cutaneous and hematologic response, but this regimen was discontinued due to toxicity and followed by a consolidation/maintenance phase with azacitidine, thus achieving a final complete response with a much higher than expected progression-free and overall survival in an elderly patient with comorbidities. This information may be useful in the design of treatment approaches for elderly patients with blastic plasmocytoid dendritic cell neoplasm. However, it should be confirmed in clinical trials as well as by optimizing the induction and extending the consolidation/maintenance period to avoid early relapses after discontinuation and improve progression-free survival. PMID:27660468

  13. [Tubulointerstitial nephritis associated with treatment with selective Cox-2 inhibitors, celecoxib and rofecoxib].

    Science.gov (United States)

    Ortiz, M; Mon, C; Fernández, M J; Sánchez, R; Mampaso, F; Alvarez Ude, F

    2005-01-01

    The nephrotoxic effect of nonselective nonsteroidal anti-inflamatory drugs (NSAIDS) has been widely described. The main benefit of the Cox-2 inhibitors in relation to the NSAIDS is the production of a very similar analgesic effect, but with fewer gastrointestinal side effects. However, their effects on renal function are little known as yet and their long-term safety is still pending definition. The use of selective Cox-2 inhibitors as anti-inflamatory analgesic is becoming more and more common in our environment. We report two cases of tubulointersticial nephritis confirmed by renal biopsy, associated with administration of the two Cox-2 inhibitors currently available on the market, celecoxib and rofecoxib. In both cases, we were talking about elderly women, with deterioration of the general condition and acute renal failure. In the former case, renal biopsy showed an acute tubulo-intersticial nephritis (TIN) so highly "variegated" in its histologic expression. In the second case, was associated with strong indications of chronicity. Treatment with steroid was initiated in both patients and improvement of renal function was observed.

  14. DFT analysis and spectral characteristics of Celecoxib a potent COX-2 inhibitor

    Science.gov (United States)

    Vijayakumar, B.; Kannappan, V.; Sathyanarayanamoorthi, V.

    2016-10-01

    Extensive quantum mechanical studies are carried out on Celecoxib (CXB), a new generation drug to understand the vibrational and electronic spectral characteristics of the molecule. The vibrational frequencies of CXB are computed by HF and B3LYP methods with 6-311++G (d, p) basis set. The theoretical scaled vibrational frequencies have been assigned and they agreed satisfactorily with experimental FT-IR and Raman frequencies. The theoretical maximum wavelength of absorption of CXB are calculated in water and ethanol by TD-DFT method and these values are compared with experimentally determined λmax values. The spectral and Natural bonds orbital (NBO) analysis in conjunction with spectral data established the presence of intra molecular interactions such as mesomeric, hyperconjugative and steric effects in CXB. The electron density at various positions and reactivity descriptors of CXB indicate that the compound functions as a nucleophile and establish that aromatic ring system present in the molecule is the site of drug action. Electronic distribution and HOMO - LUMO energy values of CXB are discussed in terms of intra-molecular interactions. Computed values of Mulliken charges and thermodynamic properties of CXB are reported.

  15. Dose-dependent reduction of 3,2'-dimethyl-4-aminobiphenyl-derived DNA adducts in colon and liver of rats administered celecoxib

    International Nuclear Information System (INIS)

    Colon cancer is second leading cause of cancer-related deaths in Western countries. Diet and smoking, which contain aromatic and heterocyclic amines, are major risk factors for colon cancer. Colorectal cancers have a natural history of long latency and therefore provide ample opportunities for effective chemoprevention. 3,2'-Dimethyl-4-aminobiphenyl (DMABP) is an experimental aromatic amine that causes cancer in rat colon and serves as an experimental model for arylamine and heterocyclic amine mutagens derived from diet and smoking. In this study, we investigated the effects of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor on DMABP-induced DNA adduct formation in rat liver and colon. Male F-344 rats (5-week old) were provided free access to modified AIN-76A rat chow containing 0 (control), 500, 1000, or 1500 ppm celecoxib. Two weeks later, the rats received a subcutaneous injection of 100 mg/kg DMABP in peanut oil. Two days after DMABP treatment, the rats were killed and DMABP-derived adducts were analyzed in colon and liver DNA by butanol extraction-mediated 32P-postlabeling. Two major DNA adducts, identified as dG-C8-DMABP and dG-N2-DMABP, were detected in liver and colon of rats treated with DMABP. These DNA adducts were diminished approximately 35-40% with 500 ppm and 65-70% with 1,000 ppm celecoxib. In the colon, no further decline in DNA adducts was observed at 1500 ppm. The same DMABP-DNA adducts also were detected in the liver and were also diminished by celecoxib treatment. The reduction in DMABP-DNA adduct levels in celecoxib-treated animals provides further support for celecoxib as a chemopreventive agent for colorectal cancer

  16. Celecoxib and Ibuprofen Restore the ATP Content and the Gluconeogenesis Activity in the Liver of Walker-256 Tumor-Bearing Rats

    Directory of Open Access Journals (Sweden)

    Camila Oliveira de Souza

    2015-07-01

    Full Text Available Background/Aims: The main purpose of this study was to investigate the effects of celecoxib and ibuprofen, both non-steroidal anti-inflammatory drugs (NSAIDs, on the decreased gluconeogenesis observed in liver of Walker-256 tumor-bearing rats. Methods: Celecoxib and ibuprofen (both at 25 mg/Kg were orally administered for 12 days, beginning on the same day when the rats were inoculated with Walker-256 tumor cells. Results: Celecoxib and ibuprofen treatment reversed the reduced production of glucose, pyruvate, lactate and urea from alanine as well as the reduced production of glucose from pyruvate and lactate in perfused liver from tumor-bearing rats. Besides, celecoxib and ibuprofen treatment restored the decreased ATP content, increased triacylglycerol levels and reduced mRNA expression of carnitine palmitoyl transferase 1 (CPT1, while ibuprofen treatment restored the reduced mRNA expression of peroxisome proliferator-activated receptor alpha (PPARα in the liver of tumor-bearing rats. Both treatments tended to decrease TNFα, IL6 and IL10 in the liver of tumor-bearing rats. Finally, the treatment with celecoxib, but not with ibuprofen, reduced the growth of Walker-256 tumor. Conclusion: Celecoxib and ibuprofen restored the decreased gluconeogenesis in the liver of Walker-256 tumor-bearing rats. These effects did not involve changes in tumor growth and probably occurred by anti-inflammatory properties of these NSAIDs, which increased expression of genes associated with fatty acid oxidation (PPARα and CPT1 and consequently the ATP production, normalizing the energy status in the liver of tumor-bearing rats.

  17. Weekly administration of docetaxel in combination with estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer: final results from a phase II study

    OpenAIRE

    Carles, J; Font, A; Mellado, B.; Domenech, M.; Gallardo, E; González-Larriba, J L; Catalan, G.; Alfaro, J; Gonzalez del Alba, A; Nogué, M; LIANES, P; Tello, J M

    2007-01-01

    The objective of this study was to evaluate the efficacy and safety profile of weekly docetaxel, estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer. Forty-eight patients received 35 mg m−2 of weekly docetaxel for 3 out of every 4 weeks, 280 mg of estramustine twice daily on days 1–3, 8–10, 15–17 and 400 mg of celecoxib twice daily until progression or toxicity. Cycles were repeated every 28 days for at least six cycles. Patients were evaluated for response...

  18. Relationship between childhood asthma andHelicobacter pyloriinfection

    Institute of Scientific and Technical Information of China (English)

    Ying Wu

    2016-01-01

    Objective:To investigate the correlation between childhood asthma andHelicobacter pylori infection.Methods: A total of 80 children with asthma who were treated in our hospital from May 2012 to May 2015 were selected as the research subjects, and 40 cases of healthy children were selected as control group, theHelicobacter pylori infection of the two groups of patients were compared, the double antibody sandwich enzyme-linked immunosorbent assay was used to detect the serumHelicobacter pylori-IgG,Helicobacter pylori-CagAIgG, IL-4,Helicobacter pylori, IFN-γ and IL-1β,etc., and the correlation betweenHelicobacter pylori infection and asthma was analyzed.Results:The positive rates ofHelicobacter pylori infection in asthma group and children in attack stage were significantly higher than those in control group and children in remission stage (P<0.05). The positive rates of serumHelicobacter pylori-IgG and Helicobacter pylori-CagAIgG in asthma group and children in attack stage were significantly lower than those in control group and children in remission stage (P<0.05). The serum levels of IFN-γ in asthma group and children in attack stage were significantly lower than those in control group and children in remission stage, IL-4 and IL-1β levels in the former were significantly higher than those in the latter (P<0.05).Helicobacter pyloriinfection positive had significant positive correlation with IL-1β concentration (r=0.75,P<0.05).Conclusions:Helicobacter pylori infection in children has significant positive correlation with the incidence of asthma, suggesting thatHelicobacter pylori infection has a certain protective effect on childhood asthma, but persistentHelicobacter pyloriinfection in children with asthma can aggravate the immune disorder, which is the main reason for the difficulty of treatment of asthma.

  19. Helicobacter pylori infection in Chile.

    Science.gov (United States)

    Figueroa, G; Acuña, R; Troncoso, M; Portell, D P; Toledo, M S; Valenzuela, J

    1997-11-01

    This article summarizes studies designed to evaluate the role of Helicobacter pylori infection in Chile, described in 21 reports from nine centers in various Chilean regions published between 1985 and 1995. According to their data, H. pylori infection is quite frequent among patients with a variety of gastric conditions, including adults (43%-92%) and children (6%-100%). Levels of specific IgG antibodies to H. pylori are also elevated among patients with duodenal ulcers (100%) and gastritis (86%) as well as asymptomatic adults (75%). Combination therapy with three (but not two) drugs has been proved effective, with clinical improvement, ulcer cure, and H. pylori eradication occurring in well-controlled studies. Available evidence suggests that antibiotic resistance is not a major problem in treatment. The H. pylori reinfection rate is low (4.2% per year), suggesting that combination therapy with three drugs constitutes a cost-effective alternative for treating colonized symptomatic patients. Concurrent preliminary studies revealed that antibodies to VacA but not CagA proteins correlate with disease severity in Chilean patients. It can be concluded that local research assists local administrators of health resources to implement adequate policies to prevent, control, and treat H. pylori-related pathologies.

  20. Treatment of Helicobacter pylori infection.

    LENUS (Irish Health Repository)

    O'Connor, Anthony

    2012-02-01

    This article aims to examine current best practice in the field reference to first-line, second-line, rescue and emerging treatment regimens for Helicobacter pylori eradication. The recommended first-line treatment in published guidelines in Europe and North American is proton pump inhibitor combined with amoxicillin and clarithromycin being the favoured regimen. Rates of eradication with this regimen however are falling alarmingly due to a combination of antibiotic resistance and poor compliance with therapy. Bismuth based quadruple therapies and levofloxacin based regimes have been shown to be effective second line regimens. Third-line options include regimes based on rifabutin or furazolidone, but susceptibility testing is the most rational option here, but is currently not used widely enough. Sequential therapy is promising but needs further study and validation outside of Italy. Although the success of first line treatments is falling, if compliance is good and a clear treatment paradigm adhered to, almost universal eradication rates can still be achieved. If compliance is not achievable, the problem of antibiotic resistance will continue to beset any combination of drugs used for H. pylori eradication.

  1. Transmission of Helicobacter pylori Infection

    Directory of Open Access Journals (Sweden)

    Giuseppina Oderda

    1999-01-01

    Full Text Available Helicobacter pylori infection is one of the most common bacterial infections worldwide. It is accepted as the major cause of chronic gastritis, peptic ulcer, carcinoma of the distal part of the stomach and gastric lymphoma. However, how and when the infection is acquired remain largely unknown. Identification of mode of transmission is vital for developing preventive measures to interrupt its spread, but studies focused on this issue are difficult to implement. From epidemiological studies, it is known that there are great differences in the prevalence of infection in different populations and in ethnic groups originating from high prevalence regions. This is likely related to inferior hygienic conditions and sanitation. In developing countries, infection occurs at a much earlier age. In developed countries, the prevalence of infection is related to poor socioeconomic conditions, particularly density of living. Humans seem to be the only reservoir of H pylori, which spread from person to person by oral-oral, fecal-oral or gastro-oral routes. Most infections are acquired in childhood, possibly from parents or other children living as close contacts. Infection from the environment or from animals cannot be entirely excluded.

  2. Comparative genomics of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Quan-Jiang Dong; Qing Wang; Ying-Nin Xin; Ni Li; Shi-Ying Xuan

    2009-01-01

    Genomic sequences have been determined for a number of strains of Helicobacter pylori (H pylori) and related bacteria.With the development of microarray analysis and the wide use of subtractive hybridization techniques,comparative studies have been carried out with respect to the interstrain differences between H pylori and inter-species differences in the genome of related bacteria.It was found that the core genome of H pylori constitutes 1111 genes that are determinants of the species properties.A great pool of auxillary genes are mainly from the categories of cag pathogenicity islands,outer membrane proteins,restriction-modification system and hypothetical proteins of unknown function.Persistence of H pylori in the human stomach leads to the diversification of the genome.Comparative genomics suggest that a host jump has occurs from humans to felines.Candidate genes specific for the development of the gastric diseases were identified.With the aid of proteomics,population genetics and other molecular methods,future comparative genomic studies would dramatically promote our understanding of the evolution,pathogenesis and microbiology of H pylori.

  3. Epidemiology of Helicobacter pylori infection.

    Science.gov (United States)

    Eusebi, Leonardo H; Zagari, Rocco M; Bazzoli, Franco

    2014-09-01

    Medline and PubMed databases were searched on epidemiology of Helicobacter pylori for the period of April 2013-March 2014. Several studies have shown that the prevalence of H. pylori is still high in most countries. In north European and North American populations, about one-third of adults are still infected, whereas in south and east Europe, South America, and Asia, the prevalence of H. pylori is often higher than 50%. H. pylori remains highly prevalent in immigrants coming from countries with high prevalence of H. pylori. However, the lower prevalence of infection in the younger generations suggests a further decline of H. pylori prevalence in the coming decades. Low socioeconomic conditions in childhood are confirmed to be the most important risk factors for H. pylori infection. Although the way the infection is transmitted is still unclear, interpersonal transmission appears to be the main route. Finally, H. pylori recurrence after successful eradication can still occur, but seems to be an infrequent event.

  4. Helicobacter pylori in gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Hyo; Jun; Ahn; Dong; Soo; Lee

    2015-01-01

    Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori(H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to theoccurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cag A and vac A are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis.

  5. Helicobacter pylori and pancreatic diseases

    Institute of Scientific and Technical Information of China (English)

    Milutin; Bulajic; Nikola; Panic; Johannes; Matthias; L?hr

    2014-01-01

    A possible role for Helicobacter pylori(H. pylori) infec-tion in pancreatic diseases remains controversial. H. pylori infection with antral predomination leading to an increase in pancreatic bicarbonate output and induc-ing ductal epithelial cell proliferation could contribute to the development of pancreatic cancer via complex interactions with the ABO genotype, dietary and smok-ing habits and N-nitrosamine exposure of the host. Although the individual study data available so far is inconsistent, several meta-analyses have reported an increased risk for pancreatic cancer among H. pylori seropositive individuals. It has been suggested that H. pylori causes autoimmune pancreatitis due to molecu-lar mimicry between H. pylori a-carbonic anhydrase(a-CA) and human CA type Ⅱ, and between H. pylori plasminogen-binding protein and human ubiquitin-protein ligase E3 component n-recognin 2, enzymes that are highly expressed in the pancreatic ductal andacinar cells, respectively. Future studies involving large numbers of cases are needed in order to examine the role of H. pylori in autoimmune pancreatitis more fully. Considering the worldwide pancreatic cancer burden, as well as the association between autoimmune pan-creatitis and other autoimmune conditions, a complete elucidation of the role played by H. pylori in the gen-esis of such conditions could have a substantial impact on healthcare.

  6. Helicobacter pylori and Nonmalignant Diseases.

    Science.gov (United States)

    Potamitis, Georgios S; Axon, Anthony T R

    2015-09-01

    Helicobacter pylori is responsible for most peptic ulcers, plays a role in functional dyspepsia and is thought by some to influence the course of gastroesophageal reflux disease. This article addresses recent studies that have been published in connection with these diseases. H. pylori-associated peptic ulcer is declining in prevalence but the incidence of perforation and bleeding remains high especially in the elderly. All H. pylori associated peptic ulcers should be treated by eradication of the infection. Dyspepsia is a common disorder that affects up to 25% of the population. About 8% of cases that are infected with H. pylori will respond to treatment of the infection. The association between H. pylori and gastroesophageal reflux disease continues to be debated, a number of studies have shown that there is a negative association between H. pylori infection and Gastroesophageal reflux disease but treatment of H. pylori has not been shown to induce reflux or to affect the response to medication. Gastric atrophy is known to extend when acid suppression is used in infected patients implying that H. pylori treatment should be used in infected patients who are to undergo long-term Proton Pump Inhibitor therapy.

  7. Diagnostic of Helicobacter pylori infection.

    Science.gov (United States)

    Mégraud, Francis; Floch, Pauline; Labenz, Joachim; Lehours, Philippe

    2016-09-01

    There is progress in endoscopy techniques. While it is not yet possible to detect Helicobacter pylori directly in the stomach, it becomes easier to detect the mucosal changes induced by the bacteria. Some small changes can also increase the sensitivity of the invasive tests, for example culture or histology, but the wide use of proton-pump inhibitors has a negative impact on these tests. Only molecular methods are able to detect a limited load of bacteria, especially by using real-time PCR but also with new methods, for example dual-priming oligonucleotide-based PCR, loop-medicated isothermal amplification, droplet-digital PCR or a multiple genetic analysis system. Among the noninvasive tests, urea breath test remains a test of major interest, while there are attempts to develop an ammonia breath test and other nanosensor devices. A new antigen stool test, a chemoluminescence immunoassay using the LIAISON apparatus has also been tested for the first time with success. Despite its limitations, serology remains the most popular test to detect H. pylori antibodies. It also allows pepsinogen dosage which is of interest for detecting atrophy. PMID:27531532

  8. Clinical, pharmacokinetic and pharmacodynamic evaluations of metronomic UFT and cyclophosphamide plus celecoxib in patients with advanced refractory gastrointestinal cancers

    OpenAIRE

    Allegrini, Giacomo; Di Desidero, Teresa; Barletta, Maria Teresa; Fioravanti, Anna; Orlandi, Paola; Canu, Bastianina; Chericoni, Silvio; Loupakis, Fotios; Di Paolo, Antonello; Masi, Gianluca; Fontana, Andrea; Lucchesi, Sara; Arrighi, Giada; GIUSIANI, MARIO; Ciarlo, Andrea

    2012-01-01

    Aims To evaluate UFT and cyclophosphamide (CTX) based metronomic chemotherapy plus celecoxib (CXB) for the treatment of patients with heavily pre-treated advanced gastrointestinal malignancies. Methods Thirty-eight patients received 500 mg/mq2 CTX i.v bolus on day 1 and, from day 2, 50 mg/day CTX p.o. plus 100 mg/twice a day UFT p.o. and 200 mg/twice a day CXB p.o. Tegafur, 5-FU, 5-FUH2, GHB and uracil pharmacokinetics were assessed. Plasma vascular endothelial growth factor (VEGF), soluble V...

  9. Alterations in gastric mucin synthesis by Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    James C, Byrd; Robert S, Bresalier

    2000-01-01

    AIM To determine the role of Helicobacter pylori in altering gastric mucin synthesis and define how thprocess relates to H. pylori-related diseases.METHODS Analyses of human gastric tissues using immunohistochemistry and in situ hybridizatiodocument the role of H. pylori in altering the composition and distribution of gastric mucins.RESULTS These data indicate a decrease in the product of the MUC5 (MUC5AC) gene and aberraexpression of MUC6 in the surface epithelium of H. pylori-infected patients. A normal pattern was restorby H. pylori eradication. Inhibition of mucin synthesis including MUC5AC and MUCl mucins by H. pvlohas been established in vitro using biochemical and Western blot analyses. This effect is not due to inhibitiof glycosylation, but results from inhibition of synthesis of mucin core structures. In vitro experiments usiinhibitors of mucin synthesis indicate that cell surface mucins decrease adhesion of H. pylori to gastepithelial cells.CONCLUSION Inhibition of mucin synthesis by H. pylori in vivo can disrupt the protective mucous layand facilitate bacterial adhesion, which may lead to increased inflammation in thc gastric epithelium.

  10. Natural transformation and recombination in Helicobacter pylori

    NARCIS (Netherlands)

    Smeets, L.C.

    2007-01-01

    Bacteriën kennen geen geslachtelijke voortplanting, ze hebben altijd één “ouder” in plaats van twee. Ze kunnen dus tijdens de voortplanting niet kruisen. Om toch erfelijke eigenschappen te kunnen uitwisselen hebben ze andere methoden. De maagbacterie Helicobacter pylori kan dit bijvoorbeeld doen doo

  11. Diagnosis and treatment of Helicobacter pylori infection

    DEFF Research Database (Denmark)

    Bytzer, Peter; Dahlerup, Jens Frederik; Eriksen, Jens Ravn;

    2011-01-01

    National Danish guidelines for the diagnosis and treatment of Helicobacter pylori (Hp) infection have been approved by the Danish Society for Gastroenterology. All patients with peptic ulcer disease, gastric cancer, and MALT lymphoma should be tested for Hp. We also recommend testing in first...

  12. Inactivation of Helicobacter pylori by Chloramination

    Science.gov (United States)

    Three strains of Helicobacter pylori (H. pylori) were studied to determine their resistance to chloramination. H. pylori is an organism listed on the U.S. Environmental Protection Agency’s (USEPA) Contaminant Control List (CCL). H. pylori was exposed to 2ppm of pre-formed monoc...

  13. Inflammation, immunity, and vaccines for Helicobacter

    DEFF Research Database (Denmark)

    Aebischer, Toni; Meyer, Thomas F; Andersen, Leif P

    2010-01-01

    Helicobacter pylori represents the major etiologic agent of gastritis, gastric, and duodenal ulcer disease and can cause gastric cancer and mucosa-associated lymphoid tissue B-cell lymphoma. It is clear that the consequences of infection reflect diverse outcomes of the interaction of bacteria...

  14. Role of solid carriers in pharmaceutical performance of solid supersaturable SEDDS of celecoxib.

    Science.gov (United States)

    Chavan, Rahul B; Modi, Sameer R; Bansal, Arvind K

    2015-11-10

    Self emulsifying drug delivery system (SEDDS) has been increasingly used for improving the oral bioavailability of poorly water soluble drugs. SEDDS can be solidified by adsorbing them on different solid carriers. In the present study, the impact of properties of solid carrier on drug release profile from solid SEDDS was investigated. Celecoxib (CEL) loaded supersaturable SEDDS (S-SEDDS) was prepared and optimized by using optimal response surface design. Optimum composition of S-SEDDS corresponded to 10:45:45% v/v ratio of oil (Capryol 90), surfactant (Tween 20) and cosurfactant (Transcutol HP) with Soluplus (40 mg) as precipitation inhibitor. Different grades of silicon dioxide were selected based on their properties like surface area, porosity and hydrophobicity-hydrophilicity, and used for preparation of solid S-SEDDS (SS-SEDDS) by adsorption method. All SS-SEDDS formulations in release studies, gave droplet size, PDI and zeta potential similar to S-SEDDS. The percent drug release after 120min from CEL powder, S-SEDDS and SS-SEDDS with Sylysia 350 fcp, Aerosil 300 Pharma, Aerosil 200 Pharma and Aerosil R 972 Pharma was found to be 0.58%, 100%, 38.44%, 9.63%, 2.53% and 5.99%, respectively. Drug release profiles were compared by using model independent methods. The differential drug release behavior of SS-SEDDS was attributed to the different physico-chemical properties of solid carriers. SS-SEDDS with Sylysia 350 fcp showed higher drug release and greater dissolution efficiency. Oral bioavailability study also demonstrated 2.34 fold increase in Cmax and 4.82 fold increase in AUC (0-24h) when compared with CEL powder. This study highlights the rational for selection of solid carriers in the formulation development of solid SEDDS. PMID:26364711

  15. Comparing various techniques to produce micro/nanoparticles for enhancing the dissolution of celecoxib containing PVP.

    Science.gov (United States)

    Homayouni, Alireza; Sadeghi, Fatemeh; Varshosaz, Jaleh; Garekani, Hadi Afrasiabi; Nokhodchi, Ali

    2014-09-01

    One of the major challenges in pharmaceutical development is the poor dissolution performance of drugs. Celecoxib (CLX) is a poorly water soluble drug with its bioavailability being limited by its poor dissolution. In this study several particle engineering methods were employed on CLX using various ratios of CLX:PVP-K30. Micro/nanoparticles of CLX:PVP were prepared by using spray drying (SD), antisolvent crystallization followed by freeze drying (CRS-FD) and spray drying (CRS-SD) techniques. The suspension obtained through antisolvent crystallization was also subjected to high pressure homogenization followed by freeze drying (HPH-FD). Particle size measurements, saturation solubility, optical and scanning electron microscopy, DSC, XRPD, FT-IR and dissolution test were performed to characterize the physicochemical and pharmaceutical properties of the samples. The results showed that spray dried samples in the presence of (50%) PVP produced spherical particles and exhibited a high dissolution rate. Interestingly in the antisolvent crystallization technique, spherical nanoparticles of drug-PVP were obtained in the range of 291-442 nm. The average particle size was dependent on the concentration of the PVP used during the crystallization process. Solid state analysis showed that these particles were completely amorphous in nature. Also interesting to note was that at concentration of 5% PVP, when the suspension of nanoparticles was subjected to the high pressure homogenization process, the crystallinity of CLX increased. Despite the partial crystallinity of particles produced, they showed excellent dissolution behavior. It can thus be concluded that the method of preparation of CLX micro/nanoparticles had a big impact on the dissolution rate when the concentration of PVP was low (e.g., 5%). At high PVP concentration (e.g., 50%) all methods used to prepare engineered CLX particles showed better dissolution with no significant differences in their dissolution

  16. A study of Helicobacter pylori infection in diabetes mellitus

    OpenAIRE

    Khwaja Saifullah Zafar; Vidyasagar Ram; Manoj Kumar

    2016-01-01

    Background: Helicobacter pylori is the most common bacterial infection in human beings. The aim was to study the association of Helicobacter pylori infection in patients of diabetes mellitus. Design of the study was observational analytic cross sectional study. Methods: A total of 69 subjects were studied. Of these 30 were non diabetics and 39 were diabetics, with disease duration more than 1 year. The serological diagnosis of H. pylori was made by Anti- Helicobacter pylori antibody test....

  17. Ghrelin and Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Hiroyuki Osawa

    2008-01-01

    Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. Ghrelin also plays an essential role in the mechanism of gastric mucosal defense. Thus, it is important to clarify which diseases primar-ily influence changes in plasma ghrelin concentrations. Helicobacter pylori(H pylori infection is involved in the pathogenesis of gastritis, gastric and duodenal ulcer, gastric carcinoma, and mucosa-associated lym-phoid tissue lymphorna. H pylori eradication is related to body weight change. Compared, H pylori infected and negative subjects with normal body mass index, plasma ghrelin concentration, gastric ghrelin mRNA, and the number of ghrelin producing cells in gastric mucosa are significantly lower in Hpylori injected sub-jects than in H pylori-negative controls. Plasma ghrelin concentration decreases with the progression of gastric atrophy. Impaired gastric ghrelin production in associa-tion with atrophic gastritis induced by Hpylori infection accounts for the decrease in plasma ghrelin concentra-tion. However, the ratio of plasma acylated ghrelin to total ghrelin levels is higher in patients with chronic atrophic gastritis than in healthy subjects. This may re-sult from the compensatory increase in plasma active ghrelin concentration in response to gastric atrophy. After H pylori eradication, gastric preproghrelin mRNA expression is increased nearly 4-fold in most cases. However, changes in plasma ghrelin concentrations be-fore and after H pylori cure are not associated with the gastric ghrelin production. Plasma ghrelin changes are inversely correlated with both body weight change and initial plasma ghrelin levels.

  18. Chronic urticaria and Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Yadav Mukesh

    2008-04-01

    Full Text Available Background: Helicobacter pylori (HP have recently emerged as a novel eliciting factor for chronic urticaria (CU. The possible association between HP and CU has enormous potential, as eradicating HP could cure CU. Aims and Objectives: We conducted a study to assess the prevalence of HP infection and effect of bacterium eradication on skin lesions in patients of chronic idiopathic urticaria (CIU. Settings and Design: Four hundred sixty patients of CU attending the allergy clinic, SMS hospital, Jaipur during the period February 6, 2004, to February 6, 2006, were screened for possible eliciting factors. Patients with CIU were enrolled and others were excluded. Materials and Methods: Sixty-eight patients of CIU and similar number of age and sex matched controls, attending the allergy clinic, SMS Hospital, Jaipur were enrolled in the study. All patients underwent endoscopy with antral biopsy for urease and histopathology to identify HP-associated gastritis. Infected patients were given HP eradication therapy. Eradication of bacterium was confirmed by fecal antigen assay. Subjective response to treatment was judged using chronic urticaria quality-of-life questionnaire (CU-Q 2 oL while objective response to treatment was judged by need for ′rescue medication′ (antihistaminics. Statistical Analysis: Data were analyzed using Chi square and paired′t′ test for their level of significance. Results: HP associated gastritis was present in 48 (70.58% patients, out of which 39 (81.25% patients responded to eradication therapy. Ten (50.00% patients without HP associated gastritis showed response to symptomatic therapy. Overall 49 (72.05% patients responded and 19 (27.94% showed no response. The value of χ2 was 28.571 (P = 0.003, which showed significant association between presence of HP and response to eradication regimen. Conclusion: The response of HP eradication therapy in infected patients of CIU is significant. HP should be included in diagnostic

  19. Polyelectrolyte coated multilayered liposomes (nanocapsules) for the treatment of Helicobacter pylori infection.

    Science.gov (United States)

    Jain, Parul; Jain, Sanyog; Prasad, K N; Jain, S K; Vyas, Suresh P

    2009-01-01

    Helicobacter pylori infection is one of the major causes of gastric cancers. A number of systems have already been reported, but 100% eradication has never been achieved. The present invention designs a gastro-retentive drug delivery system incorporated with amoxicillin and metronidazole, specifically suited for the eradication of Helicobacter pylori infections due to its mucoadhesiveness in the presence of polyelectrolyte polymers. The system possesses the advantages of both vesicular and particulate carriers, and it was prepared by alternative coating of polyanion (poly(acrylic acid), PAA) and polycation (poly(allylamine hydrochloride), PAH) using liposomes as the core. Compared with the conventional liposomes, the polyelectrolyte based multilayered system (nanocapsules) gave prolonged drug release in simulated gastric fluid, which is well suited for drug delivery against H. pylori infection in the stomach. In vitro growth inhibition study, agglutination assay, and in situ adherence assay in cultured H. pylori suggested the successful in vitro activity and binding propensity of the system. In vivo bacterial clearance study carried out in a H. pylori infected mouse model finally confirmed the success of the developed novel nanocapsule system. Thus, the newly developed composite nanocapsules along with the use of combination therapy proved to have commendable potential in Helicobacter pylori eradication as compared to already existing conventional and novel drug delivery systems. PMID:19718807

  20. Gastroinvasive Helicobacter infection in an Ocelot (Leopardus pardalis).

    Science.gov (United States)

    Kanou, Y; Fukui, D; Yamamoto, S; Shibahara, T; Ishikawa, Y; Kadota, K

    2005-11-01

    Highly invasive Helicobacter-like organisms were found in a 19-year-old female ocelot (Leopardus pardalis) with multiple ulcers in the fundic region of the stomach. The bacteria, resembling Helicobacter heilmannii, were located largely within canaliculi or in the cytosol of parietal cells. Except in the ulcerative lesions, parietal cells were hyperplastic, while chief cells and neck mucous cells were reduced in number. The term "gastroinvasive Helicobacter-like organism" was applied. It seems probable that this organism differs from other Helicobacter organisms in pathogenicity, and possible that its behaviour in vitro would help it to evade antibacterial treatment. PMID:16154138

  1. Nobeli auhinna tõi Helicobacter pylori / Juhan Kaldre

    Index Scriptorium Estoniae

    Kaldre, Juhan

    2005-01-01

    Nobeli meditsiiniauhind määrati sel aastal Austraalia teadlastele Robin Warrenile ja Barry Marshallile, kes avastasid, et gastriit ning peptiline haavand tekib Helicobacter pylori infektsiooni tulemusena

  2. [Role of animal gastric Helicobacter species in human gastric pathology].

    Science.gov (United States)

    Pozdeev, O K; Pozdeeva, A O; Pozdnyak, A O; Saifutdinov, R G

    2015-01-01

    Animal Helicobacter species other than Helicobacter pylori are also able to cause human gastritis, gastric ulcers, and MALT lymphomas. Animal Helicobacter species are presented with typical spiral fastidious microorganisms colonizing the gastric mucosa of different animals. Bacteria initially received their provisional name Helicobacter heilmannii, and out of them at least five species colonizing the gastric mucosa of pigs, cats, and dogs were isolated later on. A high proportion of these diseases are shown to be zoonotic. Transmission of pathogens occurs by contact. The factors of bacterial pathogenicity remain little studied.

  3. Pharmacokinetic drug interactions of the selective androgen receptor modulator GTx-024(Enobosarm) with itraconazole, rifampin, probenecid, celecoxib and rosuvastatin.

    Science.gov (United States)

    Coss, Christopher C; Jones, Amanda; Dalton, James T

    2016-08-01

    GTx-024 (also known as enobosarm) is a first in class selective androgen receptor modulator being developed for diverse indications in oncology. Preclinical studies of GTx-024 supported the evaluation of several potential drug-drug interactions in a clinical setting. A series of open-label Phase I GTx-024 drug-drug interaction studies were designed to interrogate potential interactions with CYP3A4 inhibitor (itraconazole), a CYP3A4 inducer (rifampin), a pan-UGT inhibitor (probenecid), a CYP2C9 substrate (celecoxib) and a BCRP substrate (rosuvastatin). The plasma pharmacokinetics of GTx-024, its major metabolite (GTx-024 glucuronide), and each substrate were characterized in detail. Itraconazole administration had no effect on GTx-024 pharmacokinetics. Likewise, GTx-024 administration did not significantly change the pharmacokinetics of celecoxib or rosuvastatin. Rifampin administration had the largest impact on GTx-024 pharmacokinetics of any co-administered agent and reduced the maximal plasma concentration (Cmax) by 23 % and the area under the curve (AUC∞) by 43 %. Probenecid had a complex interaction with GTx-024 whereby both GTx-024 plasma levels and GTx-024 glucuronide plasma levels (AUC∞) were increased by co-administration of the UGT inhibitor (50 and 112 %, respectively). Overall, GTx-024 was well tolerated and poses very little risk of generating clinically relevant drug-drug interactions. PMID:27105861

  4. DC-derived IL-18 drives Treg differentiation, murine Helicobacter pylori–specific immune tolerance, and asthma protection

    OpenAIRE

    Oertli, M; Sundquist, M; Hitzler, I; Engler, D B; Arnold, I C; Reuter, S; Maxeiner, J; Hansson, M.; Taube, C.; Quiding-Järbrink, M.; Müller, A.

    2012-01-01

    Persistent colonization with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes infected individuals to gastric cancer. Conversely, it is also linked to protection from allergic, chronic inflammatory, and autoimmune diseases. We demonstrate here that H. pylori inhibits LPS-induced maturation of DCs and reprograms DCs toward a tolerance-promoting phenotype. Our results showed that DCs exposed to H. pylori in vitro or in vivo failed to induce T cell effector fun...

  5. Differences in Surface-Exposed Antigen Expression between Helicobacter pylori Strains Isolated from Duodenal Ulcer Patients and from Asymptomatic Subjects

    OpenAIRE

    Thoreson, Ann-Catrin E.; Hamlet, Annika; Çelik, Janet; Byström, Mona; Nyström, Susanne; Olbe, Lars; Svennerholm, Ann-Mari

    2000-01-01

    We have analyzed possible qualitative and quantitative differences in antigen expression between Helicobacter pylori strains isolated from the antrum and different locations in the duodenum of 21 duodenal ulcer (DU) patients and 20 asymptomatic subjects (AS) by enzyme-linked immunosorbent assay (ELISA) and inhibition ELISA. Almost all antral and duodenal strains grown in vitro expressed the N-acetyl-neuroaminyllactose-binding hemagglutinin, flagellins (subunits FlaA and FlaB), urease, a 26-kD...

  6. Effects of Celecoxib on Interleukin-6 and Interleukin-8 Levels in Xenografted Nude Mice with Human Triple-negative Breast Cancer%塞来昔布对人三阴性乳腺癌裸鼠体内白细胞介素6和白细胞介素8水平的影响

    Institute of Scientific and Technical Information of China (English)

    王玲; 李杰; 张璟; 曹娜娜; 单保恩

    2012-01-01

    Objective To evaluate the effects of celecoxib on interleukin-6 (IL-6) and interleukin-8 (IL-8 ) expression in established nude mice with human triple-negative breast cancer (TNBC). Methods Human TNBC MDA-MB-231 cells were injected into BALB/c nude mice subcutaneously. The mice were randomly divided into 4 groups,including the control group and three celecoxib groups (receiving 25,50,100 mg·kg-1·d-1,respectively). On the 42nd day,the tumor volume and tumor weight were measured and growth curves were analyzed. The serum level of IL-6 and IL-8 was detected by ELBA assay. The mRNAs and protein levels of IL-6 and IL-8 in tumor tissues were measured by RT-PCR and immunohistochemistry, respectively. Results Compared with control group, celecoxib at doses of 25,50 and 100 mg ·kg-1·d-' inhibited the tumor growth significantly (P < 0.05). The serum levels of IL-6 and IL-8 were notably decreased in different cele- coxib treatment groups. Meanwhile, the gene expression of IL-6 and IL-8 in tumor tissues was also markedly suppressed after celecoxib treatment. Conclusion Celecoxib can inhibit the secretion and expression of IL-6 and IL-8, thus preventing the progress of TNBC in vivo.%目的探讨塞来昔布对人三阴性乳腺癌(TNBC)裸鼠体内白细胞介素6(IL-6)和IL-8水平的影响.方法 人TNBC细胞MDA-MB-231接种于裸鼠背部皮下,建立人TNBC裸鼠移植瘤模型.随机分为对照组和塞来昔布低、中、高剂量组.42 d后观察裸鼠一般状况的变化、用药前后肿瘤生长情况及肿瘤质量变化;ELISA法检测各组裸鼠血清中IL-6和IL-8含量的变化;RT-PCR检测肿瘤组织中IL-6和IL-8 mRNA的变化;免疫组化法检测肿瘤组织中IL-6和IL-8蛋白表达的变化.结果 塞来昔布各组肿瘤大小和瘤重较对照组均明显减小,差异均有统计学意义(P<0.05).经塞来昔布治疗后,塞来昔布低、中、高剂量组裸鼠血清中IL-6和IL-8的含量明显降低,与对照组

  7. 塞来昔布防治胃癌的机制及应用前景%Mechanisms and prospect of celecoxib in the prevention and treatment of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    周海存; 刘宏斌

    2013-01-01

    Gansu province is a high incidence area of gastric cancer,and the mortality caused by gastric cancer ranks first in China.A safe and effective treatment of gastric cancer is the key point in the research.In recent years,tumor-targeted therapy has become a new research direction along with the gradually increased understanding of the molecular biology of cancer mechanism.Several studies have shown that increased expression of cyclooxygenase (COX)-2 plays an important role in the occurrence and development of malignant tumor.Celecoxib,a non-steroidal anti-inflammatory drug,is a novel COX-2 selective inhibitor which can significantly reduce the incidence of gastrointestinal malignancy,and inhibit tumorigenesis through inhibiting tumor growth and tumor angiogenesis,inducing the apoptosis of tumor cells,reversing multidrug resistance,enhancing the cytotoxicity and radiosensitivity of chemotherapy drugs,and producing synergistic effects with combining chemotherapy and radiotherapy.Therefore,celecoxib has the potential to be the treatment of choice for gastric cancer.%甘肃为我国胃癌高发区,胃癌病死率居全国之首,安全有效的治疗是研究重点.近年来,随着对肿瘤分子生物学机制研究的不断深入,肿瘤的靶向治疗已成为研究的新方向.大量研究结果表明:环氧合酶(COX)的过度表达在肿瘤的发生、发展中起着重要作用,非甾体类抗炎药塞来昔布是一种新型COX-2选择性抑制剂,可明显降低消化道肿瘤的发病率.它通过抑制肿瘤生长和肿瘤新生血管生成,诱导肿瘤细胞凋亡,逆转多药耐药,增强化疗药的细胞毒作用和放射敏感性,与化、放疗产生协同作用,从而抑制肿瘤的发生、发展.因此,以COX-2为特异靶点的治疗策略有望为胃癌治疗提供新的思路,具有良好的临床应用前景.

  8. Simultaneous inhibition of EGFR/VEGFR and cyclooxygenase-2 targets stemness-related pathways in colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Araceli Valverde

    Full Text Available Despite the demonstrated benefits of anti-EGFR/VEGF targeted therapies in metastatic colorectal cancer (mCRC, many patients initially respond, but then show evidence of disease progression. New therapeutic strategies are needed to make the action of available drugs more efficient. Our study aimed to explore whether simultaneous targeting of EGFR/VEGF and cyclooxygenase-2 (COX-2 may aid the treatment and management of mCRC patients. The dual tyrosine kinase inhibitor AEE788 and celecoxib were used to inhibit EGFR/VEGFR and COX-2, respectively, in colorectal cancer cells. COX-2 inhibition with celecoxib augmented the antitumoral and antiangiogenic efficacy of AEE788, as indicated by the inhibition of cell proliferation, induction of apoptosis and G1 cell cycle arrest, down-regulation of VEGF production by cancer cells and reduction of cell migration. These effects were related with a blockade in the EGFR/VEGFR signaling axis. Notably, the combined AEE788/celecoxib treatment prevented β-catenin nuclear accumulation in tumor cells. This effect was associated with a significant downregulation of FOXM1 protein levels and an impairment in the interaction of this transcription factor with β-catenin, which is required for its nuclear localization. Furthermore, the combined treatment also reduced the expression of the stem cell markers Oct 3/4, Nanog, Sox-2 and Snail in cancer cells, and contributed to the diminution of the CSC subpopulation, as indicated by colonosphere formation assays. In conclusion, the combined treatment of AEE788 and celecoxib not only demonstrated enhanced anti-tumoral efficacy in colorectal cancer cells, but also reduced colon CSCs subpopulation by targeting stemness-related pathways. Therefore, the simultaneous targeting of EGFR/VEGF and COX-2 may aid in blocking mCRC progression and improve the efficacy of existing therapies in colorectal cancer.

  9. Simultaneous Inhibition of EGFR/VEGFR and Cyclooxygenase-2 Targets Stemness-Related Pathways in Colorectal Cancer Cells

    Science.gov (United States)

    Valverde, Araceli; Peñarando, Jon; Cañas, Amanda; López-Sánchez, Laura M.; Conde, Francisco; Hernández, Vanessa; Peralbo, Esther; López-Pedrera, Chary; de la Haba-Rodríguez, Juan; Aranda, Enrique; Rodríguez-Ariza, Antonio

    2015-01-01

    Despite the demonstrated benefits of anti-EGFR/VEGF targeted therapies in metastatic colorectal cancer (mCRC), many patients initially respond, but then show evidence of disease progression. New therapeutic strategies are needed to make the action of available drugs more efficient. Our study aimed to explore whether simultaneous targeting of EGFR/VEGF and cyclooxygenase-2 (COX-2) may aid the treatment and management of mCRC patients. The dual tyrosine kinase inhibitor AEE788 and celecoxib were used to inhibit EGFR/VEGFR and COX-2, respectively, in colorectal cancer cells. COX-2 inhibition with celecoxib augmented the antitumoral and antiangiogenic efficacy of AEE788, as indicated by the inhibition of cell proliferation, induction of apoptosis and G1 cell cycle arrest, down-regulation of VEGF production by cancer cells and reduction of cell migration. These effects were related with a blockade in the EGFR/VEGFR signaling axis. Notably, the combined AEE788/celecoxib treatment prevented β-catenin nuclear accumulation in tumor cells. This effect was associated with a significant downregulation of FOXM1 protein levels and an impairment in the interaction of this transcription factor with β-catenin, which is required for its nuclear localization. Furthermore, the combined treatment also reduced the expression of the stem cell markers Oct 3/4, Nanog, Sox-2 and Snail in cancer cells, and contributed to the diminution of the CSC subpopulation, as indicated by colonosphere formation assays. In conclusion, the combined treatment of AEE788 and celecoxib not only demonstrated enhanced anti-tumoral efficacy in colorectal cancer cells, but also reduced colon CSCs subpopulation by targeting stemness-related pathways. Therefore, the simultaneous targeting of EGFR/VEGF and COX-2 may aid in blocking mCRC progression and improve the efficacy of existing therapies in colorectal cancer. PMID:26107817

  10. Phase I study of celecoxib with concurrent irinotecan, cisplatin, and radiation therapy for patients with unresectable locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ritsuko eKomaki

    2011-12-01

    Full Text Available Purpose: Preclinical findings suggest that adding targeted therapies to combination radiation-chemotherapy can enhance treatment efficacy; however, this approach may enhance normal tissue toxicity. We investigated the maximum tolerated dose, dose-limiting toxicities, and response rate when the selective cyclo-oxygenase-2 inhibitor celecoxib is added to concurrent irinotecan, cisplatin, and radiation therapy for patients with inoperable stage II-III non-small cell lung cancer. Methods and materials: Eighteen patients were analyzed in a phase I clinical dose-escalation trial. Celecoxib was given daily beginning 5 days before radiation followed by maintenance doses for 12 weeks. Toxicity was graded with the Common Terminology Criteria for Adverse Events V3.0 and response with the World Health Organization system. Primary endpoints were maximum tolerated dose of celecoxib and treatment toxicity; secondary endpoints were response and survival rates. Results: The maximum tolerated dose of celecoxib was not reached, in part owing to discontinuation of the drug supply. At doses of 200 or 400 mg/day, no patients experienced any dose-limiting toxicity (acute grade ≥4 esophagitis or pneumonitis, neutropenic fever or thrombocytopenia requiring transfusion, or acute grade ≥3 diarrhea. Grade 3 toxicities were leukopenia (5 patients, fatigue (3, pneumonitis (2, dyspnea (1, pain (1, and esophageal stricture (1. Interestingly, pulmonary fibrosis (a late toxicity was no more severe in the higher-dose (400-mg group and may have been less common than in the lower-dose group. The clinical response rate was 100% (8 complete, 10 partial. Two-year rates were: overall survival 65%; local-regional control 69%; distant metastasis-free survival 71%; and disease-free survival 64%. Conclusions: Although preliminary, our results suggest that adding celecoxib to concurrent chemoradiation for inoperable NSCLC is safe and can improve outcome without increasing normal tissue

  11. Comparing etoricoxib and celecoxib for preemptive analgesia for acute postoperative pain in patients undergoing arthroscopic anterior cruciate ligament reconstruction: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Glabglay Prapakorn

    2010-10-01

    Full Text Available Abstract Background The efficacy of selective cox-2 inhibitors in postoperative pain reduction were usually compared with conventional non-selective conventional NSAIDs or other types of medicine. Previous studies also used selective cox-2 inhibitors as single postoperative dose, in continued mode, or in combination with other modalities. The purpose of this study was to compare analgesic efficacy of single preoperative administration of etoricoxib versus celecoxib for post-operative pain relief after arthroscopic anterior cruciate ligament reconstruction. Methods One hundred and two patients diagnosed as anterior cruciate ligament injury were randomized into 3 groups using opaque envelope. Both patients and surgeon were blinded to the allocation. All of the patients were operated by one orthopaedic surgeon under regional anesthesia. Each group was given either etoricoxib 120 mg., celecoxib 400 mg., or placebo 1 hour prior to operative incision. Post-operative pain intensity, time to first dose of analgesic requirement and numbers of analgesic used for pain control and adverse events were recorded periodically to 48 hours after surgery. We analyzed the data according to intention to treat principle. Results Among 102 patients, 35 were in etoricoxib, 35 in celecoxib and 32 in placebo group. The mean age of the patients was 30 years and most of the injury came from sports injury. There were no significant differences in all demographic characteristics among groups. The etoricoxib group had significantly less pain intensity than the other two groups at recovery room and up to 8 hours period but no significance difference in all other evaluation point, while celecoxib showed no significantly difference from placebo at any time points. The time to first dose of analgesic medication, amount of analgesic used, patient's satisfaction with pain control and incidence of adverse events were also no significantly difference among three groups. Conclusions

  12. Helicobacter pylori and Gastrointestinal Malignancies.

    Science.gov (United States)

    Venerito, Marino; Vasapolli, Riccardo; Rokkas, Theodoros; Malfertheiner, Peter

    2015-09-01

    Helicobacter pylori infection is the principal trigger of gastric carcinogenesis and gastric cancer (GC) and remains the third leading cause of cancer-related death in both sexes worldwide. In a big Japanese study, the risk of developing GC in patients with peptic ulcer disease who received H. pylori eradication therapy and annual endoscopic surveillance for a mean of 9.9 years was significantly lower after successful eradication therapy compared to the group with persistent infection (0.21%/year and 0.45%/year, respectively, p = .049). According to a recent meta-analysis, H. pylori eradication is insufficient in GC risk reduction in subjects with advanced precancerous conditions (i.e., intestinal metaplasia and dysplasia). A microsimulation model suggested screening smokers over the age of 50 in the U.S. for serum pepsinogens. This would allow to detect advanced gastric atrophy with endoscopic follow-up of subjects testing positive as a cost-effective strategy to reduce GC mortality. In a Taiwanese study, the anti-H. pylori IgG-based test-and-treat program had lower incremental cost-effectiveness ratios than that with (13)C-urea breath test in both sexes to prevent GC whereas expected years of life lost for GC were higher and the incremental cost-effectiveness ratios of test-and-treat programs were more cost-effective in young adults (30-69 years old) than in elders (>70 years old). With respect to gastrointestinal malignancies other than GC, a meta-analysis confirmed the inverse association between H. pylori infection and esophageal adenocarcinoma. In a Finnish study, H. pylori seropositivity was associated with an increased risk of biliary tract cancers (multivariate adjusted OR 2.63; 95% CI: 1.08-6.37), another meta-analysis showed a slightly increased rate of pancreatic cancer in patients with CagA-negative strains (OR: 1.30; 95% CI: 1.02-1.65), whereas current data suggest that the association between H. pylori and colorectal neoplasms may be population

  13. Helicobacter pylori neutrophil activating protein as target for new drugs against H.pylori inflammation

    Institute of Scientific and Technical Information of China (English)

    Theodora Choli-Papadopoulou; Filippos Kottakis; Georgios Papadopoulos; Stefanos Pendas

    2011-01-01

    Helicobacter pylori (H. pylori ) infection is among the most common human infections and the major risk factor for peptic ulcer disease and gastric cancer. Within this work we present the implication of C-terminal region of H. pylori neutrophil activating protein in the stimulation of neutrophil activation as well as the evidence that the C-terminal region of H. pylori activating protein is indispensable for neutrophil adhesion to endothelial cells, a step necessary to H. pylori inflammation. In addition we show that arabino galactan proteins derived from chios mastic gum, the natural resin of the plant Pistacia lentiscus var. Chia inhibit neutrophil activation in vitro .

  14. Recent "omics" advances in Helicobacter pylori.

    Science.gov (United States)

    Berthenet, Elvire; Sheppard, Sam; Vale, Filipa F

    2016-09-01

    The development of high-throughput whole genome sequencing (WGS) technologies is changing the face of microbiology, facilitating the comparison of large numbers of genomes from different lineages of a same organism. Our aim was to review the main advances on Helicobacter pylori "omics" and to understand how this is improving our knowledge of the biology, diversity and pathogenesis of H. pylori. Since the first H. pylori isolate was sequenced in 1997, 510 genomes have been deposited in the NCBI archive, providing a basis for improved understanding of the epidemiology and evolution of this important pathogen. This review focuses on works published between April 2015 and March 2016. Helicobacter "omics" is already making an impact and is a growing research field. Ultimately these advances will be translated into a routine clinical laboratory setting in order to improve public health. PMID:27531533

  15. Helicobacter Pylori Bacteremia: An Unusual Finding

    Science.gov (United States)

    De Luca, Concetta; Mancin, Annalisa; Calabrò, Maria; Daleno, Cristina; Ferrario, Antonella; Renzulli, Raffaella; Scuderi, Cristina; Casari, Erminia

    2016-01-01

    We report a case of Helicobacter pylori transient bacteremia in a woman with ulcerated antral gastric cancer. The patient was hospitalized for laparoscopy and subtotal gastrectomy. After surgery she developed fever (39°C) and was empirically treated with levofloxacin. Blood cultures, collected and sent immediately to Laboratory, were positive for a spiral Gram-negative bacterium. This isolate was identified as H. pylori and the specific susceptibility test was performed. One day after the fever was decreased but antibiotic treatment with levofloxacin was continued and it was maintained until discharge. In summary, H. pylori transient bacteremia may occur as a rare complication after stomach surgery. Further studies are necessary to elucidate the potential role of Helicobacter pylori presence in blood.

  16. A fluid model for Helicobacter pylori

    Science.gov (United States)

    Reigh, Shang-Yik; Lauga, Eric

    2015-11-01

    Swimming microorganisms and self-propelled nanomotors are often found in confined environments. The bacterium Helicobacter pylori survives in the acidic environment of the human stomach and is able to penetrate gel-like mucus layers and cause infections by locally changing the rheological properties of the mucus from gel-like to solution-like. In this talk we propose an analytical model for the locomotion of Helicobacter pylori as a confined spherical squirmer which generates its own confinement. We solve analytically the flow field around the swimmer, and derive the swimming speed and energetics. The role of the boundary condition in the outer wall is discussed. An extension of our model is also proposed for other biological and chemical swimmers. Newton Trust.

  17. Gastric leptin and Helicobacter pylori infection

    OpenAIRE

    Azuma, T; Suto, H.; Ito, Y.; Ohtani, M.; Dojo, M; Kuriyama, M; Kato, T.

    2001-01-01

    BACKGROUND—Leptin regulates feeding behaviour and therefore may be a mediator of anorexia associated with acute and chronic inflammation. Recently, leptin mRNA and leptin protein were found in the gastric epithelium.
AIM—The aim of the present study was to examine the effect of Helicobacter pylori infection on gastric leptin expression to investigate the pathophysiological role of gastric leptin.
METHODS—Surgically resected human stomach tissues were subjected to immunohistochemistry and reve...

  18. Helicobacter pylori infection and dental care.

    OpenAIRE

    Hardo, P G; Tugnait, A; Hassan, F.; Lynch, D A; West, A P; Mapstone, N P; Quirke, P.; Chalmers, D M; Kowolik, M J; Axon, A T

    1995-01-01

    Sixty two patients (mean age 45.6 years) were assessed for oral hygiene and periodontal disease by dental examination before endoscopy. Information about oral care, smoking, and dentures was obtained and samples of dental plaque collected. The presence of Helicobacter pylori in plaque as sought by culture and polymerase chain reaction (PCR), and gastric antral biopsy specimens were taken for histological examination. Although H pylori was detected in the antral specimens of 34 patients (54%) ...

  19. Helicobacter pylori and peptic ulcer disease.

    OpenAIRE

    Feldman, M; Peterson, W. L.

    1993-01-01

    Medical therapy for duodenal or gastric ulcer disease has traditionally involved gastric acid antisecretory therapy for 4 to 8 weeks to promote initial healing and indefinitely to prevent recurrences of ulcer. The discovery of Helicobacter pylori in most patients with peptic ulcer disease has led to a change in this approach. Therapy designed to eradicate H pylori may facilitate ulcer healing with acid antisecretory agents and, more important, may greatly reduce the incidence of ulcer recurre...

  20. Paf-acether synthesis by Helicobacter pylori.

    OpenAIRE

    Denizot, Y.; Sobhani, I; Rambaud, J C; M. Lewin; Thomas, Y.; Benveniste, J

    1990-01-01

    Clinical studies suggest that Helicobacter pylori may play a role in the pathogenesis of gastroduodenal ulcers in man but direct evidence of mucosal injury by this microorganism is still lacking. Paf-acether (paf) causes a number of disorders including ischaemic bowel necrosis and gastroduodenal ulceration. Since paf is produced by Escherichia coli, we investigated whether it could be synthesised by H pylori. Five H pylori isolates were collected from antral biopsy specimens from patients wit...

  1. Accuracy and economics of Helicobacter pylori diagnosis.

    OpenAIRE

    Cutler, A. F.

    1998-01-01

    Many diagnostic tests are available to establish Helicobacter pylori infection status. Most of the tests are accurate though none works perfectly, and no gold standard for diagnosis exists. Newly developed serum immunoassay kits can substitute for laboratory-based enzyme-linked immunosorbent assays, but whole blood immunoassays do not yet demonstrate adequate performance characteristics. Serologic diagnosis of H. pylori remains the most cost-effective option and should be utilized to establis...

  2. Pathophysiology and clinical relevance of Helicobacter pylori.

    OpenAIRE

    Halter, F.; Hurlimann, S.; Inauen, W

    1992-01-01

    Considerable knowledge has recently accumulated on the mechanism by which Helicobacter pylori (H. pylori) induces chronic gastritis. Although H. pylori is not an invasive bacterium, soluble surface constituents can provoke pepsinogen release from gastric chief cells or trigger local inflammation in the underlying tissue. Urease appears to be one of the prime chemoattractants for recruitment and activation of inflammatory cells. Release of cytokines, such as tumor necrosis factor alpha, interl...

  3. Neutrophil degranulation by Helicobacter pylori proteins.

    OpenAIRE

    Nøorgaard, A; Andersen, L P; Nielsen, H

    1995-01-01

    Mucosal biopsy specimens from patients with Helicobacter pylori infection in gastric antrum contain an increased amount of myeloperoxidase. This study was performed to elucidate the interaction of H pylori sonicate protein(s) and neutrophils concerning myeloperoxidase release. Neutrophil degranulation with myeloperoxidase release was examined in a direct stimulating assay. Priming activity of H pylori was examined after preincubating neutrophils in sonicate, either crude or modified by heat t...

  4. Isolation of Helicobacter pylori from saliva.

    OpenAIRE

    Ferguson, D A; C. Li; Patel, N. R.; Mayberry, W R; Chi, D S; Thomas, E.

    1993-01-01

    Helicobacter pylori was grown in low numbers from the saliva of one of nine patients who were positive for gastric H. pylori. The saliva-derived isolate from this patient was identical to the antral biopsy-derived isolate from the same patient and differed from isolates cultured from the antral biopsies of all other patients by soluble-protein electrophoresis, restriction endonuclease DNA analysis, and Southern blot hybridization. This is the first observation, to our knowledge, of the recove...

  5. Recurrent aphthous stomatitis and Helicobacter pylori

    OpenAIRE

    Gomes, Carolina-Cavaliéri; Gomez, Ricardo-Santiago; Zina, Lívia-Guimarães; Amaral, Fabrício-Rezende

    2016-01-01

    Background Recurrent aphthous stomatitis (RAS) is a recurrent painful ulcerative disorder that commonly affects the oral mucosa. Local and systemic factors such as trauma, food sensitivity, nutritional deficiencies, systemic conditions, immunological disorders and genetic polymorphisms are associated with the development of the disease. Helicobacter pylori (H. pylori) is a gram-negative, microaerophile bacteria, that colonizes the gastric mucosa and it was previously suggested to be involved ...

  6. Relation between periodontitis and helicobacter pylori infection

    OpenAIRE

    Zheng, Pei; Zhou, Weiying

    2015-01-01

    Objective: The correlation between periodontitis and Helicobacter pylori (H. pylori) infection in the mouth was analyzed. Method: 70 elderly patients with periodontitis treated at our hospital from January 2013 to December 2014 were recruited. Dental plaques and gargle were collected for H. pylori detection using PCR technique. Periodontal health status of the patients was recorded. 70 control cases with healthy periodontium were also included. The symptoms of H. pylori infection in the mouth...

  7. Helicobacter pylori and gastroesophageal reflux disease

    Directory of Open Access Journals (Sweden)

    Nigro Casimiro

    2008-07-01

    Full Text Available Abstract Background The nature of the relationship between Helicobacter pylori and reflux oesophagitis is still not clear. To investigate the correlation between Helicobacter pylori infection and GERD taking into account endoscopic, pH-metric and histopathological data. Methods Between January 2001 and January 2003 a prospective study was performed in 146 patients with GERD in order to determine the prevalence of Helicobacter pylori infection at gastric mucosa; further the value of the De Meester score endoscopic, manometric and pH-metric parameters, i.e. reflux episodes, pathological reflux episodes and extent of oesophageal acid exposure, of the patients with and without Helicobacter pylori infection were studied and statistically compared. Finally, univariate analysis of the above mentioned data were performed in order to evaluate the statistical correlation with reflux esophagitis. Results There were no statistically significant differences between the two groups, HP infected and HP negative patients, regarding age, gender and type of symptoms. There was no statistical difference between the two groups regarding severity of symptoms and manometric parameters. The value of the De Meester score and the ph-metric parameters were similar in both groups. On univariate analysis, we observed that hiatal hernia (p = 0,01, LES size (p = 0,05, oesophageal wave length (p = 0,01 and pathological reflux number (p = 0,05 were significantly related to the presence of reflux oesophagitis. Conclusion Based on these findings, it seems that there is no significant evidence for an important role for H. pylori infection in the development of GERD and erosive esophagitis. Nevertheless, current data do not provide sufficient evidence to define the relationship between HP and GERD. Further assessments in prospective large studies are warranted.

  8. Consequences of Helicobacter pylori infection in children

    Institute of Scientific and Technical Information of China (English)

    Lucia; Pacifico; Caterina; Anania; John; F; Osborn; Flavia; Ferraro; Claudio; Chiesa

    2010-01-01

    Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is lifelong. Although H. pylori typically colonizes the hu-man stomach for many decades without adverse con-sequences, children infected with H. pylori can manifest gastrointestinal diseases. Controversy persists regarding testing (and treating) for H. pylori infection in children with recurrent a...

  9. [Colonic microenvironment in familial helicobacter infection].

    Science.gov (United States)

    Shcherbakov, P L; Vorob'ev, A A; Nesvizhskiĭ, Iu V; Mitrokhin, S D; Kudriavtseva, L V; Minaev, V I; Filin, V A; Petrova, N N; Zaĭtseva, S V

    1998-01-01

    To elucidate the significance of the familial microenvironment in the genesis of Helicobacter infection, a clinical and instrumental investigation was made of 13 families selected by the probands who had digestive diseases associated with H. pylori: gastroduodenitis and duodenal ulcer disease. The occurrence of Helicobacter infection and gastritis in the family members was ascertained to be largely determined by their concurrent residence in the limited area, i.e. by the way of life. The contribution of the "family" factor in antral gastritis, fundal gastritis, and H. pylori infection was 60.0, 40.0, and about 90.0%, respectively. The patients with gastroenterological abnormalities associated with H. pylori were found to show changes in the species-specific and quantitative composition of the colonic microbiocenosis, which were symptomatic and revealed by bacteriological studies in 47.5% of cases and severe in 32.5%. When antihelicobacter therapy is planned, a through treatment of all family members and, if possible, pets should be made. Colonic microbiocenosis should be monitored while treating Helicobacter infection. PMID:9662996

  10. Effects of fucosylated milk of goat and mouse on Helicobacter pylori binding to Lewis b antigen

    Institute of Scientific and Technical Information of China (English)

    Hong-Tao Xu; Ning Li; Lennart Hammarstr(o)m; Thomas Borén; Rolf Sj(o)str(o)m; Yao-Feng Zhao; Zheng-Xing Lian; Bao-Liang Fan; Zhi-Hui Zhao; Shu-Yang Yu; Yun-Ping Dai; Li-Li Wang; Hui-Ling Niu

    2004-01-01

    AIM: To evaluate the effects of animal milk containing fucosylated antigens on Helicobacter pylori (Hpylori) binding to Lewis b antigen.METHODS: A mammary gland expression vector containing human α1-3/4-fucosyltransferase cDNA sequences was constructed. Transient expression of human α1-3/4-fucosyltransferase cDNA in goat mammary cell and establishment of transgenic mice were performed. The adhesion inhibitory properties of milk samples were analyzed by using H pylori RESULTS: Goat milk samples were found to inhibit bacterial binding to Lewis b antigen. The highest inhibition was observed 42 h after injection of the plasmid. The binding activity of Hpylori to Lewis b antigen reduced mostly, by 83%, however milk samples from transgenic mice did not inhibit H pylori binding to Lewis b antigen.CONCLUSION: The use of "humanized" animal milk produced by the transgenic introduction of fucosylated antigen can perhaps provide an alternative therapy and preventive measure for H pylori infection.

  11. Mesoporous carbon with spherical pores as a carrier for celecoxib with needle-like crystallinity: Improve dissolution rate and bioavailability

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Wenquan; Zhao, Qinfu; Sun, Changshan [Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang (China); Zhang, Zhiwen [Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203 (China); Jiang, Tongying; Sun, Jin [Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang (China); Li, Yaping [Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203 (China); Wang, Siling, E-mail: silingwang@syphu.edu.cn [Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang (China)

    2014-06-01

    The purposes of this investigation are to design mesoporous carbon (MC) with spherical pore channels and incorporate CEL to it for changing its needlelike crystal form and improving its dissolution and bioavailability. A series of solid-state characterization methods, such as SEM, TEM, DSC and XRD, were employed to systematically investigate the existing status of celecoxib (CEL) within the pore channels of MC. The pore size, pore volume and surface area of samples were characterized by nitrogen physical absorption. Gastric mucosa irritation test was carried out to evaluate the safety of mesoporous carbon as a drug carrier. Dissolution tests and in vivo pharmacokinetic studies were conducted to confirm the improvement in drug dissolution kinetics and oral bioavailability. Uptake experiments were conducted to investigate the mechanism of the improved oral bioavailability. The results of solid state characterization showed that MC was prepared successfully and CEL was incorporated into the mesoporous channels of the MC. The crystallinity of CEL in MC was affected by different loading methods, which involve evaporation method and melting method. The dissolution rate of CEL from MC was found to be significantly higher than that of pure CEL, which attributed to reduced crystallinity of CEL. The gastric mucosa irritation test indicated that the MC caused no harm to the stomach and produced a protective effect on the gastric mucosa. Uptake experiments indicated that MC enhanced the amount of CEL absorbed by Caco-2 cells. Moreover, oral bioavailability of CEL loaded within the MC was approximately 1.59-fold greater than that of commercial CEL. In conclusion, MC was a safe carrier to load water insoluble drug by controlling the crystallinity or crystal form with improvement in drug dissolution kinetics and oral bioavailability. - Highlights: • Mesoporous carbon with spherical pore structure was prepared according to the needlelike crystalline of celecoxib. • The

  12. Antimicrobial Nanotherapeutics Against Helicobacter pylori Infection

    Science.gov (United States)

    Thamphiwatana, Soracha

    Helicobacter pylori (H. pylori) infection with its vast prevalence is responsible for various gastric diseases including gastritis, peptic ulcers, and gastric malignancy. While effective, current treatment regimens are challenged by a fast-declining eradication rate due to the increasing emergence of H. pylori strains resistant to existing antibiotics. Therefore, there is an urgent need to develop novel antibacterial strategies against H. pylori. The first area of this research, we developed a liposomal nanoformulation of linolenic acid (LipoLLA) and evaluated its bactericidal activity against resistant strains of H. pylori. We found that LipoLLA was effective in killing both spiral and dormant forms of the bacteria via disrupting bacterial membranes. LipoLLA eradicated all strains of the bacteria regardless of their antibiotic resistance status. Furthermore, the bacteria did not develop drug resistance toward LipoLLA. Our findings suggest that LipoLLA is a promising antibacterial nanotherapeutic to treat antibiotic-resistant H. pylori infection. The next step, we investigated the in vivo therapeutic potential of LipoLLA for the treatment of H. pylori infection. In vivo tests further confirmed that LipoLLA was able to kill H. pylori and reduce bacterial load in the mouse stomach. LipoLLA treatment was also shown to reduce the levels of proinflammatory cytokines including interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha, which were otherwise elevated due to the H. pylori infection. Finally, toxicity test demonstrated excellent biocompatibility of LipoLLA to normal mouse stomach. Collectively, results from this work indicate that LipoLLA is a promising, new, effective, and safe therapeutic agent for the treatment of H. pylori infection. The second area is stimuli-responsive liposomes development. By adsorbing small chitosan-modified gold nanoparticles (AuChi) onto the outer surface of liposomes, we show that at gastric pH the liposomes have

  13. Assessment of PCR-DGGE for the identification of diverse Helicobacter species, and application to faecal samples from zoo animals to determine Helicobacter prevalence

    DEFF Research Database (Denmark)

    Abu Al-Soud, W.; Bennedsen, M.; On, Stephen L.W.;

    2003-01-01

    bilis and Helicobacter hepaticus in a Nile crocodile, Helicobacter cinaedi in a baboon and a red panda, and Helicobacter felis in a wolf and a Taiwan beauty snake. All of these PCR products (similar to400 bp) showed 100 % sequence similarity to 16S rDNA sequences of the mentioned species. These results...

  14. Regulation of RKIP function by Helicobacter pylori in gastric cancer.

    Directory of Open Access Journals (Sweden)

    Erika L Moen

    Full Text Available Helicobacter pylori (H. pylori is a gram-negative, spiral-shaped bacterium that infects more than half of the world's population and is a major cause of gastric adenocarcinoma. The mechanisms that link H. pylori infection to gastric carcinogenesis are not well understood. In the present study, we report that the Raf-kinase inhibitor protein (RKIP has a role in the induction of apoptosis by H. pylori in gastric epithelial cells. Western blot and luciferase transcription reporter assays demonstrate that the pathogenicity island of H. pylori rapidly phosphorylates RKIP, which then localizes to the nucleus where it activates its own transcription and induces apoptosis. Forced overexpression of RKIP enhances apoptosis in H. pylori-infected cells, whereas RKIP RNA inhibition suppresses the induction of apoptosis by H. pylori infection. While inducing the phosphorylation of RKIP, H. pylori simultaneously targets non-phosphorylated RKIP for proteasome-mediated degradation. The increase in RKIP transcription and phosphorylation is abrogated by mutating RKIP serine 153 to valine, demonstrating that regulation of RKIP activity by H. pylori is dependent upon RKIP's S153 residue. In addition, H. pylori infection increases the expression of Snail, a transcriptional repressor of RKIP. Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells.

  15. Characterization and inactivation of an agmatine deiminase from Helicobacter pylori

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Justin E.; Causey, Corey P.; Lovelace, Leslie; Knuckley, Bryan; Flick, Heather; Lebioda, Lukasz; Thompson, Paul R. (SC)

    2010-11-12

    Helicobacter pylori encodes a potential virulence factor, agmatine deiminase (HpAgD), which catalyzes the conversion of agmatine to N-carbamoyl putrescine (NCP) and ammonia - agmatine is decarboxylated arginine. Agmatine is an endogenous human cell signaling molecule that triggers the innate immune response in humans. Unlike H. pylori, humans do not encode an AgD; it is hypothesized that inhibition of this enzyme would increase the levels of agmatine, and thereby enhance the innate immune response. Taken together, these facts suggest that HpAgD is a potential drug target. Herein we describe the optimized expression, isolation, and purification of HpAgD (10-30 mg/L media). The initial kinetic characterization of this enzyme has also been performed. Additionally, the crystal structure of wild-type HpAgD has been determined at 2.1 {angstrom} resolution. This structure provides a molecular basis for the preferential deimination of agmatine, and identifies Asp198 as a key residue responsible for agmatine recognition, which has been confirmed experimentally. Information gathered from these studies led to the development and characterization of a novel class of haloacetamidine-based HpAgD inactivators. These compounds are the most potent AgD inhibitors ever described.

  16. Characterization of Helicobacter Pylori Infection in Patients with Gastric Ulcer

    Directory of Open Access Journals (Sweden)

    Marcos Félix Osorio Pagola

    2009-12-01

    Full Text Available Background: Nowadays, infection due to Helicobacter Pylori is recognized as a medical problem worldwide. It causes chronic gastritis, peptic ulcer disease, lymphatic proliferative disorders and it is a risk factor for gastric cancer. Objective: To characterize Helicobacter Pylori infection in patients with gastric ulcer and to relate this infection to gastric histological diagnoses. Methods: An observational, descriptive, correlational retrospective study in patients with gastric ulcers at the Dr.Gustavo Aldereguía Lima Hospital was carried out from January 2005 to December 2007. Endoscopy and mucous gastric biopsy were performed for the histological and diagnostic study of the infection due to Helicobacter Pylori by means of the hematoxiline-eosine and giemsa stain respectively. The sample was composed by 137 patients. Results: the frequency of infection due to Helicobacter pylori was 59,1 % prevailing in the age groups 51-60 years old (34,6 % and 61-70 yearsold. (30,8 %. The highest frequency of malignant ulcers were located at the antral region (85,7 % with predominance of Helicobacter Pylori (80 %. There was a 95 % reliability between the relationship of Helicobacter Pylori and the histological diagnoses. The patients under the diagnosis of Helicobacter Pylori showed a greater probability to present cancer (OR 4,32 IC: 0,58-39,44 and worsened chronic gastritis (OR 2,59 IC: 0,61-11,30. Chronic gastritis did not constitute a risk factor for acute gastritis(OR 0,86 IC: 0,09-7,08. Conclusions: The probability of suffering from gastric cancer, chronic gastritis and worsened chronic gastritis was greater in all those patients who presented with Helicobacter pylori infection but in this study Helicobacter pylori did not constitute a risk factor for acute gastritis

  17. Immune Homeostasis of Human Gastric Mucosa in Helicobacter pylori Infection.

    Science.gov (United States)

    Reva, I V; Yamamoto, T; Vershinina, S S; Reva, G V

    2015-05-01

    We present the results of electron microscopic, microbiological, immunohistochemical, and molecular genetic studies of gastric biopsy specimens taken for diagnostic purposes according by clinical indications during examination of patients with gastrointestinal pathology. Immune homeostasis of the gastric mucosa against the background of infection with various pathogen strains of Helicobacter pylori was studied in patients of different age groups with peptic ulcer, gastritis, metaplasia, and cancer. Some peculiarities of Helicobacter pylori contamination in the gastric mucosa were demonstrated. Immune homeostasis of the gastric mucosa in different pathologies was analyzed depending on the Helicobacter pylori genotype.

  18. Javnozdravstveni problem rezistencije bakterije Helicobacter pylori

    OpenAIRE

    Bešlić, Ivan; Baturina, Stjepan; Mihalj, Monika; Zekanović, Dražen; Ljubičić, Neven; Turčinov, Jadranko

    2016-01-01

    Eradikacija infekcije Helicobacter pylori prvi je korak u liječenju bolesti koje su povezane s ovom infekcijom. U terapijskim protokolima koriste se uobičajeno kombinacije dvaju antibiotika i jednoga lijeka koji suprimira izlučivanje želučane kiseline (inhibitor protonske pumpe – IPP). Kombinacije lijekova podijeljene su u lijekove prve linije, lijekove druge linije i lijekove treće linije, s tim da se u trećoj liniji izbor lijeka zasniva na testiranju osjetljivosti na antibiotik izoliranoga ...

  19. Research progress on Helicobacter pyloriouter membrane protein

    Institute of Scientific and Technical Information of China (English)

    Shi-He Shao; Hua Wang; Shun-Gen Chai; Li-Mei Liu

    2005-01-01

    Helicobacter pylori (H pylori), one of the most common bacterial pathogens on human beings, colonizes the gastric mucosa. In its 95 paralogous gene families, there is a large outer membrane protein (OMP) family. It includes 32 members. These OMP are important for the diagnosis, protective immunity, pathogenicity of H pylori and so on. They are significantly associated with high H pylori density,the damage of gastric mucosa, high mucosal IL-8 levels and severe neutrophil infiltration. We introduce their research progress on pathogenicity.

  20. Diagnosis and treatment of Helicobacter pylori infection

    DEFF Research Database (Denmark)

    Bytzer, Peter; Dahlerup, Jens Frederik; Eriksen, Jens Ravn;

    2011-01-01

    National Danish guidelines for the diagnosis and treatment of Helicobacter pylori (Hp) infection have been approved by the Danish Society for Gastroenterology. All patients with peptic ulcer disease, gastric cancer, and MALT lymphoma should be tested for Hp. We also recommend testing in first...... or amoxicilline. Quadruple therapy for 2 weeks with bismuthsubsalicylate, tetracycline, metronidazole and a proton pump inhibitor is recommended in case of treatment failure. Hp testing should be offered to all patients after eradication therapy but is mandatory in patients with ulcer disease, noninvasive gastric...

  1. Ursodeoxycholic acid does not interfere with in vivo Helicobacter pylori colonization O ácido ursodeoxicólico não interfere na colonização pelo Helicobacter pylori, in vivo

    Directory of Open Access Journals (Sweden)

    José Guilherme Nogueira da Silva

    2000-12-01

    Full Text Available A low frequency of Helicobacter pylori in the gastric mucosa of patients with alkaline gastritis has been reported. At the same time, it can be noted that the growth of bacteria can be inhibited by bile acids. We studied 40 patients with chronic gastritis related to Helicobacter pylori in order to determine the effect of ursodeoxycholic acid on this infection. Diagnoses of the infection and the inflammatory process were obtained by histologic study of gastric biopsies collected during endoscopy. Two groups were studied: group I received ursodeoxycholic acid - 300 mg/day, and group II received the placebo, twice a day, both for 28 days. The colonization by Helicobacter pylori and the intensity of the mononuclear and polymorphonuclear inflammatory infiltrate were determined before (time 1 and after (time 2 treatment. Ursodeoxycholic acid had no effect on the Helicobacter pylori infection. A significant reduction in the intensity of the mononuclear inflammatory infiltrate of the gastric antrum mucosa was observed in patients from group I, when we compared not only times 1 and 2 but also groups I and II. However, this was not the case with the body mucosa. We concluded that ursodeoxycholic acid had no action on the colonization by Helicobacter pylori or on the polymorphonuclear inflammatory infiltrate, but it caused a significant reduction in the intensity of the mononuclear inflammatory infiltrate of the gastric antrum.Tem sido relatada uma baixa freqüência da infecção pelo Helicobacter pylori na mucosa gástrica de pacientes portadores de gastrite alcalina. Ao mesmo tempo, foi observada inibição do crescimento da bactéria, in vitro, pelos ácidos biliares. Com o objetivo de avaliar o efeito do ácido ursodeoxicólico sobre a colonização da mucosa gástrica por este microorganismo foram estudados 40 pacientes com gastrite crônica relacionada ao Helicobacter pylori. O diagnóstico da infecção e do processo inflamatório foi realizado por

  2. Helicobacter pylori arginase mutant colonizes arginase Ⅱ knockout mice

    Institute of Scientific and Technical Information of China (English)

    Songhee H Kim; Melanie L Langford; Jean-Luc Boucher; Traci L Testerman; David J McGee

    2011-01-01

    AIM: To investigate the role of host and bacterial argi-nases in the colonization of mice by Helicobacter pylori (H. Pylori).METHODS: H. Pylori produces a very powerful urease that hydrolyzes urea to carbon dioxide and ammonium, which neutralizes acid. Urease is absolutely essential to H. Pylori pathogenesis; therefore, the urea substrate must be in ample supply for urease to work efficiently. The urea substrate is most likely provided by arginase activity, which hydrolyzes L-arginine to L-ornithine and urea. Previous work has demonstrated that H. Pylori arginase is surprisingly not required for colonization of wild-type mice. Hence, another in vivo source of the critical urea substrate must exist. We hypothesized that the urea source was provided by host arginase Ⅱ, since this enzyme is expressed in the stomach, and H. Pylori has previously been shown to induce the expres-sion of murine gastric arginase Ⅱ. To test this hypoth-esis, wild-type and arginase (rocF) mutant H. Pylori strain SS1 were inoculated into arginase Ⅱ knockout mice. RESULTS: Surprisingly, both the wild-type and rocF mutant bacteria still colonized arginase Ⅱ knock-out mice. Moreover, feeding arginase Ⅱ knockout mice the host arginase inhibitor S-(2-boronoethyl)-L-cysteine (BEC), while inhibiting > 50% of the host arginase Ⅰactivity in several tissues, did not block the ability of the rocF mutant H. Pylori to colonize. In con-trast, BEC poorly inhibited H. Pylori arginase activity. CONCLUSION: The in vivo source for the essential urea utilized by H. Pylori urease is neither bacterial arginase nor host arginase Ⅱ; instead, either residual host arginase Ⅰor agmatinase is probably responsible.

  3. 3rd BRAZILIAN CONSENSUS ON Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Luiz Gonzaga Coelho

    2013-04-01

    Full Text Available Significant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

  4. Helicobacter pylori infection and gastrointestinal symptoms on Chilean pregnant women

    Directory of Open Access Journals (Sweden)

    Gina Ferrer Poveda

    2014-07-01

    Full Text Available Objective: the aim of this research was to determine the prevalence of Helicobacter pylori infection on Chilean pregnant women and its relationship with the appearance and severity of hyperemesis and dyspepsia. Methods: quantitative study of prevalence in a transversal cut with variable analysis. The sample was taken from 274 Chilean pregnant women from the Bío Bío province through vein puncture between June and December, 2005. Pregnant women were informed of this study, interviewed and signed an informed consent. The samples were processed using ImmunoComb II Helicobacter pylori IgG kit. Statistical analysis was performed by means of the Statistical Package for Social Sciences (SPSS Program. Results: out of the total number of pregnant women, 68.6% showed infection by Helicobacter pylori. 79.6% of the total sample had symptoms of dyspepsia, and 72.5% of this group presented Helicobacter pylori infection. 12.4% showed pregnancy hyperemesis; among them, 79.4% were infected with Helicobacter pylori. 73.4% of the pregnant women that showed gastric discomfort during the first three months had Helicobacter pylori infection. 53.7% of them continued with gastric discomfort after the first three months; of those, 95.8% were infected. Helicobacter pylori infection was present only in 1.5% of pregnant women without gastric discomfort. Conclusion: both, gastric discomfort of pregnant women and the continuity of severe symptoms of dyspepsia and hyperemesis after the first three months of gestation are significantly correlated with Helicobacter pylori infection.

  5. Indications for treatment of Helicobacter pylori infection: a systematic overview.

    OpenAIRE

    Veldhuyzen van Zanten, S J; Sherman, P.M.

    1994-01-01

    OBJECTIVE: To determine (a) the advantages and disadvantages of treatment options for the eradication of Helicobacter pylori and (b) whether eradication of H. pylori is indicated in patients with duodenal ulcer, nonucler dyspepsia and gastric cancer. DATA SOURCES: A MEDLINE search for articles published in English between January 1983 and December 1992 with the use of MeSH terms Helicobacter pylori (called Campylobacter pylori before 1990) and duodenal ulcer, gastric cancer, dyspepsia and cli...

  6. Characterization of Patients with Helicobacter pylori-Negative Peptic Ulcers

    OpenAIRE

    Roberto Hernández Conde; Guillermo Noa Pedroso; Carlos Domínguez Álvarez; Isabel Mora Díaz; Marcos Félix Osorio Pagola; Yagén Pomares Pérez

    2013-01-01

    Background: the rate of Helicobacter pylori-negative ulcers is increasing. Treatment with nonsteroidal anti-inflammatory drugs and other ulcerogenic drugs plays a significant role.Objective: to characterize patients with Helicobacter pylori-negative peptic ulcer. Methods: a case series study of patients attended by the Gastroenterology Service of the Hermanos Ameijeiras Hospital was conducted in the year 2009. Demographic, epidemiological, clinical, endoscopic and histological variables were ...

  7. 3rd Brazilian consensus on Helicobacter pylori 3º Consenso Brasileiro para Estudo do Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Luiz Gonzaga Coelho

    Full Text Available Significant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.Os avanços significativos ocorridos desde o Segundo Consenso Brasileiro sobre H. pylori realizado em 2004, em São Paulo, justificam este terceiro consenso. O evento foi organizado pelo Núcleo Brasileiro para Estudo do Helicobacter, departamento da Federação Brasileira de Gastroenterologia, tendo sido realizado em Bento Gonçalves, RS, nos dias 12 a 15 de abril de 2011. Contou com a participação de 30 delegados provenientes das cinco regiões brasileiras e um convidado internacional, incluindo gastroenterologistas

  8. Diversity of zoonotic enterohepatic Helicobacter species and detection of a putative novel gastric Helicobacter species in wild and wild-born captive chimpanzees and western lowland gorillas.

    Science.gov (United States)

    Flahou, Bram; Modrý, David; Pomajbíková, Kateřina; Petrželková, Klára J; Smet, Annemieke; Ducatelle, Richard; Pasmans, Frank; Sá, Rui M; Todd, Angelique; Hashimoto, Chie; Mulama, Martin; Kiang, John; Rossi, Mirko; Haesebrouck, Freddy

    2014-11-01

    A number of Helicobacter species cause gastrointestinal or hepatic disease in humans, including H. pylori, gastric non-H. pylori helicobacters from animal origin and enterohepatic Helicobacter species. Little is known on the presence of Helicobacter species in great apes, our closest living relatives and potential reservoirs of microorganisms that might emerge in humans. The aim of the present study was to investigate the presence of gastric and enterohepatic Helicobacter species in African chimpanzees and gorillas. Fresh fecal samples were collected from wild endangered chimpanzees and critically endangered western lowland gorillas from different African National Parks, as well as wild-born captive animals from primate sanctuaries. Intact Helicobacter bacteria were demonstrated in feces by fluorescence in situ hybridization. Screening using a Helicobacter genus-specific PCR revealed the presence of Helicobacter DNA in the majority of animals in all groups. Cloning and sequencing of 16S rRNA gene fragments revealed a high homology to sequences from various zoonotic enterohepatic Helicobacter species, including H. cinaedi and H. canadensis. A number of gorillas and chimpanzees also tested positive using PCR assays designed to amplify part of the ureAB gene cluster and the hsp60 gene of gastric helicobacters. Phylogenetic analysis revealed the presence of a putative novel zoonotic gastric Helicobacter taxon/species. For this species, we propose the name 'Candidatus Helicobacter homininae', pending isolation and further genetic characterization. The presence of several Helicobacter species not only implies a possible health threat for these endangered great apes, but also a possible zoonotic transmission of gastric and enterohepatic helicobacters from these primate reservoirs to humans. PMID:25248691

  9. Effect of Helicobacter Pylori Eradication on Extent of Duodenal Gastric Metaplasia and Grade of Gastritis

    OpenAIRE

    Bago, J; Strinić, D.; Belošić Halle, Ž.; Jandrić, D.; Tomić, M.; Bilić, A.; Bago, P.

    2002-01-01

    The extent of the regression of duodenal gastric metaplasia (DGM) after the eradication of Helicobacter pylori infection is controversial. Therefore, we decided to assess the degree of DGM before, sex weeks and one year after H. pylori eradication. 105 consecutive Helicobacter pylori positive patients with endoscopically proven duodenal ulcer, with DGM and Helicobacter pylori infection were recruited for this study. The diagnosis of Helicobacter pylori infection was based on CL...

  10. Atrophic gastric changes in both Helicobacter felis and Helicobacter pylori infected mice are host dependent and separate from antral gastritis.

    OpenAIRE

    Sakagami, T; Dixon, M; O'Rourke, J; Howlett, R.; Alderuccio, F; Vella, J; Shimoyama, T; Lee, A.

    1996-01-01

    BACKGROUND/AIMS: The role of host factors has been neglected in studies of the pathogenesis of Helicobacter associated disease. The aim of this study was to assess the response of different mouse strains to infection with a single strain of Helicobacter felis. METHOD: Six strains of inbred mice were infected with the identical H felis culture and were killed at one month, two months, and six months after infection to assess histopathological changes. In addition, two strains of mice were infe...

  11. Reflux esophagitis triggered after Helicobacter pylori eradication: a noteworthy demerit of eradication therapy among the Japanese?

    Directory of Open Access Journals (Sweden)

    Katsunori eIijima

    2015-06-01

    Full Text Available In the February 2013 Revision of Insured Medical Treatment, bacterial eradication for all Helicobacter pylori-positive individuals in Japan was covered under the insurance scheme. However, reflux esophagitis is believed to occur in approximately 10% of Japanese patients who undergo eradication therapy. Hence, the risk of reflux esophagitis among such cases should be carefully considered, particularly in the treatment for H. pylori-positive patients who are otherwise healthy. The eradication of Helicobacter pylori in cases of H. pylori-positive gastritis markedly suppresses gastric inflammation, and inhibits gastric mucosal atrophy and its progression to intestinal metaplasia. In a long-term follow-up study (10-20 years, eradication treatment was found to reduce the risk of subsequent gastric cancer. However, the fact that eradication-induced reflux esophagitis could increase the long-term risk of Barrett’s esophagus and esophageal adenocarcinoma should also be considered in the Japanese population. Appropriate treatment with proton pump inhibitors should be taken into consideration for patients undergoing eradication therapy in clinical practice.

  12. Development of Probiotics Adjuvant Therapy on Infection of Helicobacter Pylori%微生态制剂辅助治疗幽门螺杆菌感染的研究进展

    Institute of Scientific and Technical Information of China (English)

    吕志发; 谢勇

    2013-01-01

    幽门螺杆菌与多种胃肠道疾病相关,如消化性溃疡、慢性胃炎、胃黏膜相关淋巴瘤、胃癌等.目前随着传统三联方案及其他方案的广泛使用,幽门螺杆菌的耐药率越来越高,根除率日益下降.微生态制剂可以通过同幽门螺杆菌竞争结合位点、抑制幽门螺杆菌所致炎症反应、提高黏膜的免疫能力、产生抑制幽门螺杆菌物质、加强黏膜屏障功能等,抑制幽门螺杆菌的生长;同时可以减轻抗幽门螺杆菌治疗方案引起的不良反应,因此可安全地用于幽门螺杆菌感染的辅助治疗.%Helicobacter pylori are closely associated with various gastrointestinal diseases, such as peptic ulcer, chronic gastritis, gastric mucosal - associated lymphatic tissue lymphoma and gastric cancer. Recently, with triple therapy and other eradication regimens being widely used, the Helicobacter pylori resistance rates to antibiotics are getting higher, and the eradication efficacy is decreasing. Probiotics can inhibit the growth of Helicobacter pylori through binding the site in epithelial cells and restraining inflammation reaction induced by Helicobacter pylori, and it can improve the immune ability and barrier of mucosa, and can produce some substances that can inhibit Helicobacter pylori. Probiotics can also decrease the side effects of eradication regimens. Therefore, it can be safely used to adjuvant therapy for eradicating Helicobacter pylori.

  13. In situ intestinal permeability and in vivo oral bioavailability of celecoxib in supersaturating self-emulsifying drug delivery system.

    Science.gov (United States)

    Song, Woo Heon; Yeom, Dong Woo; Lee, Dong Hoon; Lee, Kyung Min; Yoo, Hyun Joon; Chae, Bo Ram; Song, Seh Hyon; Choi, Young Wook

    2014-05-01

    In order to characterize the in situ intestinal permeability and in vivo oral bioavailability of celecoxib (CXB), a poorly water-soluble cyclooxygenase (COX)-2 inhibitor, various formulations including the self-emulsifying drug delivery system (SEDDS) and supersaturating SEDDS (S-SEDDS) were compared. The S-SEDDS formulation was obtained by adding Soluplus as a precipitation inhibitor to SEDDS, composed of Capryol 90 as oil, Tween 20 as surfactant, and Tetraglycol as cosurfactant (1:4.5:4.5 in volume ratio). An in situ single pass intestinal perfusion study in rats was performed with CXB-dissolved solutions at a concentration of 40 μg/mL. The effective permeability (Peff) of CXB in the control solution (2.5 v/v% Tween 20-containing PBS) was 6.39 × 10(-5) cm/s. The Peff value was significantly increased (P drug level was measured by LC-MS/MS. The relative bioavailabilities of SEDDS and S-SEDDS were 263 and 355 %, respectively, compared to the CXB suspension as a reference. In particular, S-SEDDS revealed the highest Cmax and the smallest Tmax, indicating rapid and enhanced absorption with this formulation. This study illustrates the potential use of the S-SEDDS formulation in the oral delivery of poorly water-soluble compounds. PMID:23852645

  14. Effect of Bacterial Flora on Postimmunization Gastritis following Oral Vaccination of Mice with Helicobacter pylori Heat Shock Protein 60

    OpenAIRE

    Yamaguchi, Hiroyuki; Osaki, Takako; Taguchi, Haruhiko; Sato, Noriko; Toyoda, Atushi; Takahashi, Motomichi; Kai, Masanori; Nakata, Noboru; Komatsu, Akio; Atomi, Yutaka; Kamiya, Shigeru

    2003-01-01

    In order to assess the efficacy of oral Helicobacter pylori heat shock protein 60 (HSP60) as a vaccine, protection against H. pylori infection in specific-pathogen-free (SPF) C57BL/6 and germfree (GF) IQI mice was examined. Prophylactic oral vaccination of these two strains of mice with either H. pylori HSP60 or Escherichia coli GroEL inhibited H. pylori colonization by 90 to 95% at 3 weeks postinfection (p.i.). However, these mice were only partially protected because bacterial loads increas...

  15. Local Secretory Immunoglobulin A and Postimmunization Gastritis Correlate with Protection against Helicobacter pylori Infection after Oral Vaccination of Mice

    OpenAIRE

    Goto, Takayuki; Nishizono, Akira; Fujioka, Toshio; Ikewaki, Junko; Mifune, Kumato; Nasu, Masaru

    1999-01-01

    C57BL/6 mice were orally immunized with five weekly doses of 2 mg, 200 μg, or 2 μg of Helicobacter pylori (Sydney strain) whole-cell sonicate combined with cholera toxin. One week after the last vaccination, mice were challenged with 5 × 107 CFU of live H. pylori three times at 2-day intervals. At 6 or 18 weeks after the challenge, mice were sacrificed and bacterial cultures and histological studies of the stomach were performed. Vaccination with 2 mg/session or 200 μg/session inhibited H. py...

  16. First-line eradication of Helicobacter pylori:Are the standard triple therapies obsolete? A different perspective

    Institute of Scientific and Technical Information of China (English)

    Gyrgy; Miklós; Buzás

    2010-01-01

    Studies concerning the eradication of Helicobacter pylori have resulted in a proliferation of meta-analyses. To date, there are 303 meta-analyses cited in PubMed, 113 dealing with the therapy of the infection. A chronological analysis of the results of meta-analyses performed between 1998 and 2010 shows that first-line standard triple therapies achieved eradication rates on an intention-to-treat basis of around 80%; prolonging treatment to 14, but not 10 d should improve the results. The proton pump inhibit...

  17. Correlation of Helicobacter pylori and gastric carcinoma.

    Directory of Open Access Journals (Sweden)

    Khanna A

    2002-01-01

    Full Text Available BACKGROUND: Difference of opinion about the prevalence of H. pylori association with gastric cancer exists in the literature. AIMS: To study the correlation of Helicobacter pylori (H. pylori to gastric carcinoma. METHODS: 50 proved cases of gastric cancer were studied by rapid urease test, culture, histopathology and ELISA test for H. pylori IgG. RESULTS: 68% of cases of gastric cancer were found to be positive for H. pylori infection as compared to 74% of healthy controls. CONCLUSIONS: The prevalence rate of H. pylori infection in our patients of gastric cancer was lower than in the control population though statistically not significant, suggesting that H. pylori may not be responsible for gastric carcinogenesis in this population.

  18. Antimicrobial susceptibility pattern of Helicobacter suis strains.

    Science.gov (United States)

    Vermoote, Miet; Pasmans, Frank; Flahou, Bram; Van Deun, Kim; Ducatelle, Richard; Haesebrouck, Freddy

    2011-12-15

    Helicobacter suis is a very fastidious porcine gastric pathogen, which is also considered to be of zoonotic importance. In vitro antimicrobial susceptibility cannot be determined using standard assays, as this agent only grows in a biphasic medium with an acidic pH. Therefore, a combined agar and broth dilution method was used to analyse the activity of nine antimicrobial agents against nine H. suis isolates. After 48 h microaerobic incubation, minimal inhibitory concentrations (MICs) were determined by software-assisted calculation of bacterial growth. Only for enrofloxacin a bimodal distribution of MICs was demonstrated, indicating acquired resistance in one strain, which showed an AGT→AGG (Ser→Arg) substitution at codon 99 of gyrA. In conclusion, the assay developed here is suitable for determination of the antimicrobial susceptibility of H. suis isolates, although activity of acid sensitive antimicrobial agents may be higher than predicted from MIC endpoints. PMID:21733643

  19. Treatment of Helicobacter pylori infection 2011.

    LENUS (Irish Health Repository)

    O'Connor, Anthony

    2012-02-01

    This article reviews the literature published pertaining to Helicobacter pylori eradication over the last year. The general perception among clinicians and academics engaged in research on H. pylori has been that eradication rates for first-line therapies are falling, although some data published this year have cast doubt on this. The studies published this year have therefore focussed on developing alternative strategies for the first-line eradication of H. pylori. In this regard, clear evidence now exists that both levofloxacin and bismuth are viable options for first-line therapy. The sequential and "concomitant" regimes have also been studied in new settings and may have a role in future algorithms also. In addition, data have emerged that the probiotic Saccharomyces boulardii may be a useful adjunct to antibiotic therapy. Other studies promote individualized therapies based on host polymorphisms, age, and other such demographic factors.

  20. Does Helicobacter pylori affect portal hypertensive gastropathy?

    Directory of Open Access Journals (Sweden)

    Al Mofleh Ibrahim

    2007-01-01

    Full Text Available Helicobacter pylori (H. pylori is a major etiological factor of peptic ulcer disease (PUD. It is supposed to be a risk factor for the more frequently encountered PUD in patients with liver cirrhosis. Several investigators have evaluated the effect of H. pylori on liver cirrhosis, portal hypertensive gastropathy (PHG and encephalopathy with controversial results. Some reports have shown a higher seroprevalence and suggested a synergistic effect of H. pylori on liver cirrhosis and PHG. However, this increased prevalence is associated with a negative histology and is not influenced by the cause of cirrhosis, PHG, Child class or gender. Most studies have not found any correlation between H. pylori and PHG. In contrast, other studies have reported a markedly lower prevalence of H. pylori in cirrhotics with duodenal ulcer compared to controls. The aim of this article is to review the relationship between H. pylori infection and portal hypertensive gastropathy and the role of H. pylori eradication in cirrhotic patients.

  1. Helicobacter pylori therapy: a paradigm shift.

    Science.gov (United States)

    Graham, David Y; Dore, Maria Pina

    2016-06-01

    Helicobacter pylori (H. Pylori) is a leading cause of gastroduodenal disease, including gastric cancer. H. pylori eradication therapies and their efficacy are summarized. A number of current treatment regimens will reliably yield >90% or 95% cure rates with susceptible strains. None has proven to be superior. We show how to predict the efficacy of a regimen in any population provided one knows the prevalence of antibiotic resistance. As with other infectious diseases, therapy should always be susceptibility-based. Susceptibility testing should be demanded. We provide recommendations for empiric therapies when that is the only option and describe how to distinguish studies providing misinformation from those providing reliable and interpretable data. When treated as an infectious disease, high H. pylori cure rates are relatively simple to reliably achieve. PMID:27077447

  2. Alcohol consumption and Helicobacter pylori infection

    DEFF Research Database (Denmark)

    Brenner, H; Berg, Gabriele; Lappus, N;

    1999-01-01

    Alcohol has strong antimicrobial activity and stimulates gastric acid secretion. Alcohol consumption may therefore compromise the living conditions of Helicobacter pylori in the stomach. We assessed the relation of alcohol consumption with H. pylori infection among 1,785 participants ages 18......-88 in the German National Health and Nutrition Survey. Detailed information on dietary and lifestyle habits was obtained in personal interviews using a standardized food frequency questionnaire. Serum samples were analyzed for H. pylori immunoglobulin G antibodies by enzyme-linked immunosorbent assay. Overall...... prevalence of H. pylori infection was 39.2%. There was a clear inverse dose-response-relation between reported alcohol consumption and H. pylori infection. The relation persisted after control for potential confounding factors. The adjusted prevalence ratios (95% confidence intervals) for H. pylori infection...

  3. Helicobacter pylori infection and serum ferritin

    DEFF Research Database (Denmark)

    Berg, Gabriele; Bode, G; Blettner, M;

    2001-01-01

    OBJECTIVE: Helicobacter pylori may possibly affect the iron metabolism by occult bleeding, impaired absorption of non-hem iron, and by scavenging hem iron or ferritin, as some studies have suggested. The aim of this study was to analyze the association between H. pylori infection and serum ferritin...... in 1987/1988. The examination included a detailed questionnaire on medical history and lifestyle factors, a 7-day food record, and blood samples. Infection with H. pylori was measured serologically by ELISA and Westernblot. RESULTS: In total, 39.2% of 1806 persons aged 18 to 89 yr included in the study...... were H. pylori positive, of whom 57.6% had an infection with a CagA-positive H. pylori strain. Age- and sex-adjusted geometric mean of ferritin was 54.5 microg/dl among H. pylori-infected compared with 63.8 microg/dl among uninfected persons. A multiple linear regression model with log...

  4. Distribution of Helicobacter pylori in north China

    Institute of Scientific and Technical Information of China (English)

    Yue-Hua Gong; Ying Wang; Yuan Yuan

    2005-01-01

    AIM: To compare the distribution of virulence-associatedgenotypes of Helicobacter pylori(H pylori) in two areas of north China with different gastric cancer risk and furthermore probe into the pathogenicity of the bacterium. METHODS: Gastric biopsies were taken from 355 subjects from Zhuanghe, a high risk area of gastric cancer, and 136 subjects from Shenyang, a low risk area of gastric cancer. A total of 149 H pylori strains isolated from these patients were studied by PCR for differences in the genotypes of cagA, vac A, and iceA.RESULTS: In patients with high risk for gastric cancer, higher frequencies of vacA s1 or s1m1b genotypes were found as compared to those from the low risk area. CONCLUSION: There is significantly different distribution of H pylori genotypes between Zhuanghe and Shenyang areas in north China.

  5. Role of Helicobacter pylori in functional dyspepsia

    Institute of Scientific and Technical Information of China (English)

    Colm O'Morain

    2006-01-01

    The aetiology of dyspepsia is unknown in the majority of patients. Helicobacter pylori(H pylori) is the cause in a subset of patients. A non invasive test to assess the presence of H pylori is recommended in the management of patients under the age of 50 presenting to a family practitioner with dyspepsia. A urea breath test or a stool antigen test are the most reliable non invasive tests. Eradication of H pylori will reduce the risk to the patient with dyspepsia of developing a peptic ulcer, reduce the complication rate if prescribed nonsteroid anti-inflammatory drugs and later reduce the risk of gastric cancer. The recommended treatment for non ulcer dyspepsia associated with a H pylori infection should be a 10-d course of treatment with a PPI and two antibiotics. Treatment efficacy should be assessed four weeks after completing treatment with a urea breath test or a stool antigen test.

  6. Effect of the Vacuolation of Helicobacter Pylori

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Cytotoxic test in vitro combined with cytochemical stain, fluorescent stain, transmission electronmicrograph was used to study the vacuolated effect by helicobacter pylori (H.pylori) (Toxin+) and its pathological mechanism. 78.26 % patients with peptic ulcer associated with H.pylori was infected with H.pylori (Toxin+), while 42.86 % patients with gastritis was infected with H.pylori (Toxin+). It was positive in vacuole with acridine orange and acid phosphatase stain. Transmission electronmicrograph of vacuole revealed the presence of abounding membrane. There was a closed relationship between infection with H.pylori (Toxin+) and peptic ulcer disease. The vacuole induced by H.pylori (Toxin+) was autophagosome, which was pathological phenomenon induced by toxin.

  7. Helicobacter pylori therapy:Present and future

    Institute of Scientific and Technical Information of China (English)

    Vincenzo; De; Francesco; Enzo; Ierardi; Cesare; Hassan; Angelo; Zullo

    2012-01-01

    Helicobacter pylori(H.pylori) plays a crucial role in the pathogenesis of chronic active gastritis,peptic ulcer and gastric mucosa-associated lymphoid tissue-lymphoma,and is also involved in carcinogenesis of the stomach.H.pylori treatment still remains a challenge for physicians,since no current first-line therapy is able to cure the infection in all treated patients.Several factors may help in the eradication of therapy failure.We reviewed both bacterial and host factors involved in therapeutic management of the H.pylori infection.In addition,we evaluated data on the most successful therapy regimens-sequential and concomitant therapies-currently available for H.pylori eradication.

  8. Helicobacter pylori's cholesterol uptake impacts resistance to docosahexaenoic acid.

    Science.gov (United States)

    Correia, Marta; Casal, Susana; Vinagre, João; Seruca, Raquel; Figueiredo, Ceu; Touati, Eliette; Machado, José C

    2014-05-01

    Helicobacter pylori colonizes half of the world population and is associated with gastric cancer. We have previously demonstrated that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid known for its anti-inflammatory and antitumor effects, directly inhibits H. pylori growth in vitro and in mice. Nevertheless, the concentration of DHA shown to reduce H. pylori mice gastric colonization was ineffective in vitro. Related to the auxotrophy of H. pylori for cholesterol, we hypothesize that other mechanisms, in addition to DHA direct antibacterial effect, must be responsible for the reduction of the infection burden. In the present study we investigated if DHA affects also H. pylori growth, by reducing the availability of membrane cholesterol in the epithelial cell for H. pylori uptake. Levels of cholesterol in gastric epithelial cells and of cholesteryl glucosides in H. pylori were determined by thin layer chromatography and gas chromatography. The consequences of epithelial cells' cholesterol depletion on H. pylori growth were assessed in liquid cultures. We show that H. pylori uptakes cholesterol from epithelial cells. In addition, DHA lowers cholesterol levels in epithelial cells, decreases its de novo synthesis, leading to a lower synthesis of cholesteryl glucosides by H. pylori. A previous exposition of H. pylori to cholesterol influences the bacterium response to the direct inhibitory effect of DHA. Overall, our results suggest that a direct effect of DHA on H. pylori survival is modulated by its access to epithelial cell cholesterol, supporting the notion that cholesterol enhances the resistance of H. pylori. The cholesterol-dependent resistance of H. pylori to antimicrobial compounds raises new important aspects for the development of new anti-bacterial strategies. PMID:24447914

  9. Helicobacter pylori resistance to metronidazole and clarithromycin in Ireland.

    LENUS (Irish Health Repository)

    O'connor, Anthony

    2012-02-01

    INTRODUCTION: Helicobacter pylori eradication rates have fallen considerably in recent years. Antibiotic resistance is thought to be rising. OBJECTIVES: To examine the levels of resistance to metronidazole (MTZ) and clarithromycin (CLA) in H. pylori, isolates were taken in a reference centre in Ireland from 2007 to 2008 and were compared to a similar cohort from a study in 1997. METHOD: Antimicrobial susceptibilities were tested by E-test. Frequencies of spontaneous metronidazole and clarithromycin resistance were measured on an agar plate containing the antibiotics at concentrations of 2x and 4x minimum inhibition concentration values. Clinical data were obtained from charts, laboratory and endoscopy reports. RESULTS: Two hundred and twenty-two patients were analyzed, 98 were females. Colonies amenable to culture were grown in 219 patients. Thirty-seven had prior attempts at eradication therapy (all with amoxicillin-CLA-proton pump inhibitor. A total of 31.5% of the patients had strains resistant to MTZ and 13.2% of the patients were noted to have strains resistant to CLA. About 8.6% of the patients had strains resistant to both the agents. CLA resistance was 9.3% in those who had no prior eradication therapy compared with 32.4% of those who had. CLA resistance increased from 3.9%, among treatment-naive patients in 1997, to 9.3% in our study. MTZ resistance was 29.1% in the treatment-naive population. In 1997, MTZ resistance in the treatment-naive cohort was 27.1%. MTZ resistance was more likely to occur in females (35.4 vs. 28.5%) than in males. CONCLUSION: This study shows that resistance to CLA among Irish patients infected with H. pylori has increased since 1997. The future of treatment may well lie in the widespread use of sensitivity testing before the treatment. This would promote an accurate treatment.

  10. Helicobacter pylori and other Helicobacter species DNA in human bile samples from patients with various hepato-biliary diseases

    Institute of Scientific and Technical Information of China (English)

    Santosh K Tiwari; Aleem A Khan; Mohd Ibrahim; Mohd Aejaz Habeeb; C Ml Habibullah

    2006-01-01

    AIM: To investigate the presence of Helicobacter species by nested PCR of 16S rRNA genes followed by the presence of Helicobacter pylori (H pylori) 16S rRNA, ureA, cagA genes in bile obtained at endoscopic retrograde cholangio-pancreatography (ERCP) from 60Indian subjects.METHODS: Sixty bile samples were obtained from patients diagnosed with various hepato-biliary diseases and control subjects at ERCP. PCR analysis was carried out using primers for Helicobacter genus 16S rRNA gene and H pylori(16S rRNA, ureA and caaA) genes. Gastric Hpyloristatus was also assessed from biopsies obtained at endoscopy from patients with various hepato-biliary diseases and controls. The control group mainly consisted of subjects with gastric disorders. Sequencing analysis was performed to confirm that PCR products with 16S rRNA and cagA primers were derived from H pylori.RESULTS No Helicobacters were grown in culture from the bile samples. Helicobacter DNA was detected in bile of 96.7% and 6.6% of groups Ⅰ and Ⅱ respectively. Ten from group Ⅰ were positive for 16S rRNA and ureA and 9were positive for cagA gene. In contrast of the 2 from the control, 1 amplified with 16S rRNA, ureA and cagA primers used. The sequences of the 16S rRNA genes and cagA were 99% similar to Helicobacter pylori.CONCLUSION: Helicobacters are associated with the pathogenesis of various hepato-biliary disorders.

  11. A phase Ⅱ clinical trial of celecoxib combined with platinum-based chemotherapy in the treatment of patients with advanced NSCLC as first-line treatment

    Directory of Open Access Journals (Sweden)

    Zhijie WANG

    2008-06-01

    Full Text Available Background and objective Currently, platinum-based regimes are standard first-line chemotherapy for non-small cell lung cancer. The aim of this study is to evaluate the efficacy, influencing factors and adverse events of celecoxib plus platinum-based chemotherapy in advanced non-small cell lung cancer as first-line treatment. Methods Previously untreated patients of advanced non-small cell lung cancer with COX-2 positive, confirmed by immunohistochemical staining, were randomized to receive GP, NP or TP regimens. Celecoxib of 400 mg Bid was given, po 5-7 days before chemotherapy,and not stopped until evidence of disease progression or toxicity. Adverse events were cirtified according to NCI-CTC criteria. Kaplan-Meier method was used to analyze the survival rate. COX regression was used to define the predictive factors. Primary endpoint: median survival time, 1-year survival rate and median progression free survival time. Secondary endpoint: response rate and toxicity. Results Forty-four evaluable patients were enrolled in the study from February 2005 to March 2007. Response rate was 45%, disease control rate 59%. Median progression free survival time and median survival time were 6months (95%CI: 4-8 months and 18 months (95%CI: 9-27months, respectively. One-year survival rate was 68%. Numbers of chemotherapy cycles and overall evaluation were the predictive factors for PFS in COX model (P=0.023 and 0.000. No factor was defined to affect survival time. Neutropenia and nausea/vomit were the most common toxicity. Conclusion Celecoxib combined with platinum-based chemotherapy appears to be well tolerated and demonstrates encouraging activity in patients of previously untreated advanced NSCLC.

  12. Helicobacter hepaticus induces an inflammatory response in primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Moritz Kleine

    Full Text Available Helicobacter hepaticus can lead to chronic hepatitis and hepatocellular carcinoma in certain strains of mice. Until now the pathogenic role of Helicobacter species on human liver tissue is still not clarified though Helicobacter species identification in human liver cancer was successful in case controlled studies. Therefore we established an in vitro model to investigate the interaction of primary human hepatocytes (PHH with Helicobacter hepaticus. Successful co-culturing of PHH with Helicobacter hepaticus was confirmed by visualization of motile bacteria by two-photon-microscopy. Isolated human monocytes were stimulated with PHH conditioned media. Changes in mRNA expression of acute phase cytokines and proteins in PHH and stimulated monocytes were determined by Real-time PCR. Furthermore, cytokines and proteins were analyzed in PHH culture supernatants by ELISA. Co-cultivation with Helicobacter hepaticus induced mRNA expression of Interleukin-1 beta (IL-1β, Tumor necrosis factor-alpha, Interleukin-8 (IL-8 and Monocyte chemotactic protein-1 (MCP-1 in PHH (p<0.05 resulting in a corresponding increase of IL-8 and MCP-1 concentrations in PHH supernatants (p<0.05. IL-8 and IL-1β mRNA expression was induced in monocytes stimulated with Helicobacter hepaticus infected PHH conditioned media (p<0.05. An increase of Cyclooxygenase-2 mRNA expression was observed, with a concomitant increase of prostaglandin E2 concentration in PHH supernatants at 24 and 48 h (p<0.05. In contrast, at day 7 of co-culture, no persistent elevation of cytokine mRNA could be detected. High expression of intercellular adhesion molecule-1 on PHH cell membranes after co-culture was shown by two-photon-microscopy and confirmed by flow-cytometry. Finally, expression of Cytochrome P450 3A4 and albumin mRNA were downregulated, indicating an impairment of hepatocyte synthesis function by Helicobacter hepaticus presence. This is the first in vitro model demonstrating a pathogenic

  13. Helicobacter pylori Infection and Anemia in Taiwanese Adults

    Directory of Open Access Journals (Sweden)

    Hsiang-Yao Shih

    2013-01-01

    Full Text Available Background. Chronic Helicobacter pylori infection and iron-deficiency anemia (IDA are common in adults. Although the most common causes of IDA usually arise from the gastrointestinal tract, the association between chronic Helicobacter pylori infection and anemia remains unclear. Aim. To evaluate the association of chronic Helicobacter pylori infection and IDA. Materials and Methods. We enrolled 882 patients from January 2010 to April 2013. The status of Helicobacter pylori (H.p infection was confirmed and blood samples from the same participants were taken on the same day to check the level of hemoglobin, serum iron, ferritin, and total iron-binding capacity (TIBC. Results. No significant difference was noted from the demographic data. The average level of hemoglobin (Hb was not different between negative and positive groups, pos 13.57 g/dL versus neg 13.65 g/dL (P=0.699. Although the levels of serum IDA related parameters were expected in positive group (lower serum iron and ferritin and higher TIBC these differences did not reach statistical significance (P=0.824 for iron, P=0.360 for ferritin, and P=0.252 for TIBC. Conclusion. Chronic Helicobacter pylori infection is not attributed to IDA. The levels of hemoglobin, serum iron and ferritin, and TIBC remain unaffected after chronic H.p infection. Large-scale clinical studies are needed to prove the association.

  14. Helicobacter pylori in colorectal neoplasms: is there an aetiological relationship?

    Directory of Open Access Journals (Sweden)

    Tharakan Joseph

    2007-05-01

    Full Text Available Abstract Background This pilot study was carried out to determine whether Helicobacter pylori can be detected in normal colon or in association with colorectal neoplasia. Methods Paraffin processed colonic tissue blocks of normal colonic mucosa (n = 60, and patients diagnosed as adenoma (n = 60, and adenocarcinoma (n = 60 were retrieved from our archive; the adenoma group included tubular (n = 20, tubulovillous (n = 20 and villous adenomas (n = 20. 4 μm sections were stained by immunohistochemical methods using anti-Helicobacter pylori antibodies (polyclonal NCL-HPp and monoclonal NCL-C-jejuni. Results Significant numbers of Helicobacter pylori were identified in tubular adenomas (OR = 11.13; 95%CI = 1.62–76.70, tubulovillous adenomas (OR = 10.45; 95%CI = 1.52–71.52 and adenocarcinomas (OR = 8.13; 95%CI = 1.40–46.99 compared to controls: there was no association in numbers of Helicobacter pylori and villous adenomas (OR = 2.95; 95%CI = 0.29–9.96. Conclusion We conclude that although, in this pilot study, there appears to be an association in the prevalence of Helicobacter pylori with some, but not all, colorectal neoplasms, we can not infer causality from these results. These findings need to be further substantiated with a prospective study and the use of molecular biological techniques to determine a causal association.

  15. Correlation between Helicobacter pylori infection and atherothrombotic stroke

    Institute of Scientific and Technical Information of China (English)

    Xu Yang; Xiaoli Zhao; Yongjun Gao; Zhidong Zheng; Jilai Li; Jichen Du; Xinyi Li; Xianhao Xu; Yingying Su

    2011-01-01

    Previous studies have demonstrated that Helicobacterpylod infection is associated with coronary atherosclerotic heart disease, but the correlation between Helicobacter pylori infection and ischemic stroke remains unclear.The present study assessed the effects of Helicobacter pylori infection on atherothrombotic stroke.This study included 115 individuals with atherothrombotic stroke, all of whom were patients receiving treatment at the Department of Neurology, Aerospace Central Hospital (Aerospace Clinical Medical College Affiliated to Peking University) in China, from March 2006 to July 2009.In addition, 131 controls without the history of cardiovascular disease,cerebrovascular disease or atherothrombosis were also enrolled in the study.Results show that the Helicobacter pylori-IgG positive rate was greater in the atherothrombotic stroke patients than in the controls, but the difference was not statistically significant (67.8% vs.61.8%, OR=1.301,95%CI:0.769-2.203, P= 0.327).After correction for potential risk factors for Helicobacter pylori infection and known risk factors for ischemic stroke, no significant difference was detected between them (OR= 1.278, 95%Cl: 0.667-2.449, P= 0.459).These results indicate that there is no specific correlation between Helicobacter pylori infection and atherothrombotic stroke.This finding requires further verification in large-sample prospective studies.

  16. Efecto de la melatonina y el celecoxib sobre el estrés oxidativo en la carcinogénesis colónica experimental

    OpenAIRE

    Zaragoza Velasco, Natividad

    2016-01-01

    El cáncer colorrectal (CCR) constituye un problema sanitario mundial. Celecoxib (CEL) inhibe la incidencia de adenocarcinomas colónicos, mientras que melatonina (MEL) modula el estrés oxidativo e inhibe la COX-2. EL objetivo del estudio fue investigar el efecto de la administración de ambos sobre el estrés oxidativo y la producción de lesiones en un modelo de carcinogénesis colónica experimental. CCR fue inducido con azoximetano (AOM) en ratas Wistar. MEL y/o CEL fue administra...

  17. 塞来昔布乳膏的制备及质量控制%Preparation and Quality Control of Celecoxib Cream

    Institute of Scientific and Technical Information of China (English)

    郑江萍; 王永惠; 李鹂

    2011-01-01

    目的 制备塞来昔布乳膏并建立其质量控制方法.方法 以油酸为透皮吸收促进剂,用二甲亚砜作溶剂,制备水包油型乳膏;用高效液相色谱法测定主药含量.结果 制得的乳膏均匀细腻,易涂布;建立的色谱方法能排除辅料对塞来昔布的干扰,塞来昔布质量浓度在2.054~205.4μg/mL范围内与峰面积线性关系良好(Y=0.492X-0.1005,r=0.99999),平均回收率为99.34%,RSD=0.37%(n=9).结论 塞来昔布乳膏制备方法简单,制得的乳膏符合要求;质量控制方法可靠.%Objective To prepare Celecoxib Cream and to establish its quality control method. Methods With oleic acid as the skin penetration enhancer and dimethylsulfoxide as solution medium of celecoxib, the oil- in- water type cream was prepared. The main drug content was determined by HPLC. Results The prepared cream was uniform, smooth and fine, which was easily to be coated. The established chromatographic method was enabled to eliminate the interference of auxiliary material to celecoxib. The concentration of celecoxib showed the linearity in the range of 2. 054 ~ 205.4 μg/mL( Y = 0. 492 X - 0. 100 5, r = 0. 999 99). The average recovery rate was 99. 34% with RSD of 0.37% (n=9). Conclusion The preparation technique is simple and the prepared cream meets the requirement with the reliable quality control method.

  18. Detection of Helicobacter spp. in the saliva of dogs with gastritis.

    Science.gov (United States)

    Jankowski, M; Spużak, J; Kubiak, K; Glińska-Suchocka, K; Biernat, M

    2016-01-01

    The aim of this study was to identify the species and determine the prevalence of gastric Helicobacter in the saliva of dogs with gastritis. The study was carried out on 30 dogs of different breeds, genders and ages, which were diagnosed with gastritis. The nested-PCR method was used to detect Helicobacter spp. in saliva. Helicobacter bacteria were found in the saliva samples of 23 (76.6%) dogs. Helicobacter heilmannii was the most commonly detected species of gastric Helicobacter spp. in canine saliva, and was found in 22 (73.3%) cases. The results indicate that gastric Helicobacter spp. occurs relatively frequently in dogs with gastritis. Moreover, the saliva of dogs with gastritis may be a source of Helicobacter spp. infection for humans and other animals. However, further studies are needed to confirm this finding as the PCR method does not distinguish active from inactive infections. PMID:27096797

  19. Anti-Helicobacter pylori activity of plant extracts traditionally used for the treatment of gastrointestinal disorders

    Directory of Open Access Journals (Sweden)

    Laura Lúcia Cogo

    2010-06-01

    Full Text Available The antibacterial activity of plant extracts obtained from Bixa orellana L., Chamomilla recutita L., Ilex paraguariensis A. St.-Hil., Malva sylvestris L., Plantago major L. and Rheum rhaponticum L. has been evaluated against two reference strains and eleven clinical isolates of Helicobacter pylori. All the plant species chosen are used in popular Brazilian cuisine and folk medicine in the treatment of gastrointestinal disorders. Initial screening was made by the disk diffusion test and then minimum inhibitory concentration was determined by the agar dilution method. The results presented in this work demonstrated that among the plant preparations analyzed, B. orellana L., C. recutita L., I. paraguariensis A. St.-Hil. and M. sylvestris L. were capable of inhibiting the in vitro growth of H. pylori.

  20. Anti-Helicobacter pylori activity of plant extracts traditionally used for the treatment of gastrointestinal disorders.

    Science.gov (United States)

    Cogo, Laura Lúcia; Monteiro, Cristina Leise Bastos; Miguel, Marilis Dallarmi; Miguel, Obdulio Gomes; Cunico, Miriam Machado; Ribeiro, Marcelo Lima; de Camargo, Eloá Ramalho; Kussen, Gislene Maria Botão; Nogueira, Keite da Silva; Costa, Libera Maria Dalla

    2010-04-01

    The antibacterial activity of plant extracts obtained from Bixa orellana L., Chamomilla recutita L., Ilex paraguariensis A. St.-Hil., Malva sylvestris L., Plantago major L. and Rheum rhaponticum L. has been evaluated against two reference strains and eleven clinical isolates of Helicobacter pylori. All the plant species chosen are used in popular Brazilian cuisine and folk medicine in the treatment of gastrointestinal disorders. Initial screening was made by the disk diffusion test and then minimum inhibitory concentration was determined by the agar dilution method. The results presented in this work demonstrated that among the plant preparations analyzed, B. orellana L., C. recutita L., I. paraguariensis A. St.-Hil. and M. sylvestris L. were capable of inhibiting the in vitro growth of H. pylori.

  1. Cellular vacuoles induced by Helicobacter pylori originate from late endosomal compartments.

    Science.gov (United States)

    Papini, E; de Bernard, M; Milia, E; Bugnoli, M; Zerial, M; Rappuoli, R; Montecucco, C

    1994-01-01

    Pathogenic strains of Helicobacter pylori cause progressive vacuolation and death of epithelial cells. To identify the nature of vacuoles, the distribution of markers of various membrane traffic compartments was studied. Vacuoles derive from the endocytic pathway since they include the fluid-phase marker Lucifer yellow. Early endosome markers such as rab5, transferrin, and transferrin receptor, as well as the lysosomal hydrolase cathepsin D, are excluded from these structures. In contrast, the vacuolar membrane is specifically stained by affinity-purified antibodies against rab7, a small GTPase, localized to late endosomal compartments. The labeling of rab7 on vacuolar membranes increases as vacuolation progresses, without a concomitant increase of cellular rab7. Cell vacuolation is inhibited by the microtubule-depolymerizing agents nocodazole and colchicine. Taken together, these findings indicate that the vacuoles specifically originate from late endosomal compartments. Images PMID:7937879

  2. Anti-Helicobacter pylori activity of plant extracts traditionally used for the treatment of gastrointestinal disorders.

    Science.gov (United States)

    Cogo, Laura Lúcia; Monteiro, Cristina Leise Bastos; Miguel, Marilis Dallarmi; Miguel, Obdulio Gomes; Cunico, Miriam Machado; Ribeiro, Marcelo Lima; de Camargo, Eloá Ramalho; Kussen, Gislene Maria Botão; Nogueira, Keite da Silva; Costa, Libera Maria Dalla

    2010-04-01

    The antibacterial activity of plant extracts obtained from Bixa orellana L., Chamomilla recutita L., Ilex paraguariensis A. St.-Hil., Malva sylvestris L., Plantago major L. and Rheum rhaponticum L. has been evaluated against two reference strains and eleven clinical isolates of Helicobacter pylori. All the plant species chosen are used in popular Brazilian cuisine and folk medicine in the treatment of gastrointestinal disorders. Initial screening was made by the disk diffusion test and then minimum inhibitory concentration was determined by the agar dilution method. The results presented in this work demonstrated that among the plant preparations analyzed, B. orellana L., C. recutita L., I. paraguariensis A. St.-Hil. and M. sylvestris L. were capable of inhibiting the in vitro growth of H. pylori. PMID:24031496

  3. Helicobacter pylori γ-Glutamyltranspeptidase Induces Tolerogenic Human Dendritic Cells by Activation of Glutamate Receptors.

    Science.gov (United States)

    Käbisch, Romy; Semper, Raphaela P; Wüstner, Stefanie; Gerhard, Markus; Mejías-Luque, Raquel

    2016-05-15

    Helicobacter pylori infection is characterized by chronic persistence of the bacterium. Different virulence factors, including H. pylori γ-glutamyltranspeptidase (gGT), have been reported to induce tolerogenicity by reprogramming dendritic cells (DCs). gGT is present in all bacterial isolates, indicating an important role for gGT in the course of infection. In the current study, we have analyzed the effect of H. pylori gGT on human DCs and the subsequent adaptive immune response. We show that glutamate produced due to H. pylori gGT enzymatic activity tolerizes DCs by inhibiting cAMP signaling and dampening IL-6 secretion in response to the infection. Together, our results provide a novel molecular mechanism by which H. pylori manipulates the host's immune response to persist within its host. PMID:27183641

  4. The GyrA encoded gene: A pertinent marker for the phylogenetic revision of Helicobacter genus.

    Science.gov (United States)

    Ménard, Armelle; Buissonnière, Alice; Prouzet-Mauléon, Valérie; Sifré, Elodie; Mégraud, Francis

    2016-03-01

    Phylogeny of Epsilonproteobacteria is based on sequencing of the 16S rRNA gene. However, this gene is not sufficiently discriminatory in Helicobacter species and alternative markers would be useful. In this study, the 16S rRNA, gyrA, hsp60, gyrB, and ureA-ureB gene sequences, as well as GyrA, HSP60 and GyrB protein sequences were analyzed as tools to support Helicobacter species phylogeny: 72 Helicobacter strains, belonging to 41 species of which 36 are validated species, were included. Results of the phylogenetic reconstructions of the GyrA gene encoded protein (approximately 730 residues) indicated the most stable trees to bootstrap resampling with a good separation of Helicobacter taxa, especially between gastric and enterohepatic species. Moreover, the GyrA tree revealed high similarity with that of the gyrB and ureA-ureB genes (restricted to urease-positive Helicobacter species). However, some differences in clustering were observed when compared to the hsp60 and 23S rRNA gene trees. Altogether, these revised phylogenies (except the 16S rRNA gene for enterohepatic Helicobacters) enabled reliable clustering of Helicobacter cinaedi and 'Flexispira' strains, determined a reliable position for Helicobacter mustelae (except the hsp60 gene) and for novel Helicobacter species proposed such as 'Helicobacter sanguini', 'Helicobacter apodemus' or 'Helicobacter winghamensis', and suggest that Helicobacter species MIT 09-6949 and MIT 05-5293 isolated from rodents constitute novel species. Although they are not commonly used to study the phylogeny of Epsilonproteobacteria, protein sequences and, in particular, the GyrA protein sequence may constitute pertinent phylogenetic markers for Helicobacter genus.

  5. Preparation and characterization of celecoxib solid dispersions; comparison of poloxamer-188 and PVP-K30 as carriers

    Directory of Open Access Journals (Sweden)

    Alireza Homayouni

    2014-05-01

    Full Text Available Objective(s:Solid dispersion formulation is the most promising strategy to improve oral bioavailability of poorly water soluble drugs. The aim of this study was to compare the effect of polyvinylpyrrolidone K30 (PVP and poloxamer-188 (PLX as carrier in solid dispersion formulations of celecoxib (CLX. Materials and Methods: Solid dispersions of CLX:PVP or CLX:PLX were prepared at different ratios (2:1, 1:1, 1:2, 1:4, 1:6 by solvent evaporation and melting methods, respectively. The characterization of samples was performed using differential scanning calorimetery (DSC, X-Ray powder diffraction (XRPD and Fourier transform infrared spectroscopy (FT-IR. The Gordon-Taylor equation was used to estimate the Tg of solid dispersion systems and the possibility of the interaction between CLX and PVP. Also, the dissolution rate of all samples was determined. Results: DSC and XRPD analyses confirmed the presence of amorphous state of drug in solid dispersion systems. FT-IR studies showed CLX could participate in hydrogen bonding with PVP whilst no specific interaction between CLX and PLX was observed. Both PVP and PLX enhanced the dissolution rate of drug in solid dispersion samples. The dissolution rate was dependent on the ratio of drug: carrier. Interestingly, the solid dispersion samples of PLX at 2:1 and 1:1 drug: carrier showed slower dissolution rate than pure CLX, whilst these results were not observed for PVP. Conclusion: The effect of PVP on dissolution rate enhancement was more pronounced compared to the other carrier. Having a higher Tg and more effect on dissolution rate, PVP could be considered as a more suitable carrier compared to PLX in solid dispersion formulation of CLX.

  6. Omeprazole and misoprostol for preventing gastric mucosa effects caused by indomethacin and celecoxib in rats Omeprazol e misoprostol na prevenção de lesões de mucosa gástrica causadas por indometacina e celecoxib em ratos

    Directory of Open Access Journals (Sweden)

    Míriam Elias Cavallini

    2006-06-01

    Full Text Available PURPOSE: To evaluate and to compare macro and microscopically the intense injuries of the gastric mucosa of rats which were caused by NSAIDS celecoxib and indomethacin and the gastric cytoprotection with omeprazole and misoprostol. METHODS: The sample is formed by one hundred and fifty Wistar rats with average weight 200 g, distributed in four groups, such as: Group A, subdivided in groups A1 and A2 - pre-treatment with omeprazole (20 mg/rat during seven days and on the 8th day - use of NSAIDS, concerning A1 (20 rats were given celecoxib (1mg/rat and A2 (20 rats were given indomethacin. The Group B, subdivided in group B1 and B2 - pre-treatment with misoprostol (20mg/rat during seven days and on the 8th day use of NSAIDS, concerning B1 (20 rats were given celecoxib (1 mg/ rat and B2 (20 rats were given indomethacin (12.5 mg/rat. The Group C: were not given cytoprotection during seven days, from the 7th to the 8th day - fast of food and water ad libitum, on the 8th day of NSAIDS use, concerning C1 (20 rats were given celecoxib, C2 (20 rats were given indomethacin (12.5 mg/ rat, C3 (20 rats were given celecoxib (200mg/rato, and Group D - control group, concerning 10 rats were observed during seven days ingesting food and water ad libitum. On the 9th day, the stomachs were taken out and were macro and microscopically evaluated for the identification of the gastric injuries. RESULTS: On the macroscopic studies, the groups A2, B2 and C2 presented a remarkable high number of injuries for cm² /animal, respectively 18.55 injuries for cm² /animal, 16.25 injuries for cm² /animal and 13.55 injuries for cm²/animal. On the microscopic studies, the percentage of the injured mucosa, presented expressive difference among the groups A1, B1, C1 when compared to the groups A2, B2, C2 (pOBJETIVO: Avaliar e comparar macro e microscopicamente as lesões agudas da mucosa gástrica de ratos provocadas pelos AINEs celecoxib e indometacina e a citoproteção g

  7. Sulfonamide inhibition studies of the η-class carbonic anhydrase from the malaria pathogen Plasmodium falciparum.

    Science.gov (United States)

    Vullo, Daniela; Del Prete, Sonia; Fisher, Gillian M; Andrews, Katherine T; Poulsen, Sally-Ann; Capasso, Clemente; Supuran, Claudiu T

    2015-02-01

    The η-carbonic anhydrases (CAs, EC 4.2.1.1) were recently discovered as the sixth genetic class of this metalloenzyme superfamily, and are so far known only in protozoa, including various Plasmodium species, the causative agents of malaria. We report here an inhibition study of the η-CA from Plasmodium falciparum (PfCA) against a panel of sulfonamides and one sulfamate compound, some of which are clinically used. The strongest inhibitors identified were ethoxzolamide and sulthiame, with KIs of 131-132 nM, followed by acetazolamide, methazolamide and hydrochlorothiazide (KIs of 153-198 nM). Brinzolamide, topiramate, zonisamide, indisulam, valdecoxib and celecoxib also showed significant inhibitory action against PfCA, with KIs ranging from 217 to 308 nM. An interesting observation was that the more efficient PfCA inhibitors are representative of several scaffolds and chemical classes, including benzene sulfonamides, monocyclic/bicyclic heterocyclic sulfonamides and compounds with a more complex scaffold (i.e., the sugar sulfamate derivative, topiramate, and the coxibs, celecoxib and valdecoxib). A comprehensive inhibition study of small molecules for η-CAs is needed as a first step towards assessing PfCA as a druggable target. The present work identifies the first known η-CA inhibitors and provides a platform for the development of next generation novel PfCA inhibitors. PMID:25533402

  8. Does Helicobacter pylori eradication play a role in immune thrombocytopenia?

    Science.gov (United States)

    Llovet, Valentina; Rada, Gabriel

    2016-01-01

    Helicobacter pylori infection has been implicated as trigger or disease modifier in immune thrombocytopenia (ITP). So, eradication treatment for this agent could have clinical benefits. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews comprising 40 studies addressing the question of this article overall, including one randomized controlled trial. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded Helicobacter eradication might decrease risk of bleeding in patients with immune thrombocytopenia but the certainty of the evidence is low. PMID:27603101

  9. Helicobacter urease: Niche construction at the single molecule level

    Indian Academy of Sciences (India)

    Shahid Khan; Asim Karim; Shaheryar Iqbal

    2009-10-01

    The urease of the human pathogen, Helicobacter pylori, is essential for pathogenesis. The ammonia produced by the enzyme neutralizes stomach acid; thereby modifying its environment. The dodecameric enzyme complex has high affinity for its substrate, urea. We compared urease sequences and derivative 3D homology model structures from all published Helicobacter genomes and an equal number of genomes belonging to strains of another enteric bacterium, Escherichia coli. We found that the enzyme’s architecture adapts to fit its niche. This finding, coupled to a survey of other physiological features responsible for the bacterium’s acid resistance, suggests how it copes with pH changes caused by disease onset and progression.

  10. Detecció d'Helicobacter pylori en aigua

    OpenAIRE

    Queralt i Díaz, Núria

    2013-01-01

    [cat] Aquesta Tesi Doctoral té com objectius principals l’estudi d’Helicobacter pylori en mostres aquàtiques de Catalunya, en aigües procedents de sistemes dentals de consultes de dentistes, en saliva i en femtes de pacients amb símptomes gastrointestinals mitjançant el mètode de la PCR. També es va estudiar la supervivència d’Helicobacter pylori en aigua dolça usant un model de laboratori aplicant diferents tècniques d’anàlisi i es va interpretar el canvi de morfologia, la viabilitat i la cu...

  11. 塞来昔布预防肌腱粘连的实验研究%Experimental study of celecoxib prevention of tendon adhesions

    Institute of Scientific and Technical Information of China (English)

    孙士温; 陆永江; 孙海军; 吴迎波; 杜永军; 赵胡瑞

    2011-01-01

    目的 探讨塞来昔布对肌腱粘连及肌腱愈合的影响.方法 健康新西兰大白兔54只,随机分为3组:塞来昔布组、布洛芬组、生理盐水组.建立肌腱断裂模型,术后塞来昔布组口服塞来昔布[20 mg/(kg·d)]、布洛芬组口服布洛芬[75 mg/(kg·d)]、生理盐水组予生理盐水.术后4、8周取材,分别进行大体观察、组织学观察、生物力学检测.结果 (1)大体观察:塞来昔布组及布洛芬组随着时间的推移,肌腱均塑形好,表面光滑,并覆以薄膜样组织,容易分离,而生理盐水组随着时间的推移,肌腱与周围组织中等致密粘连,分离较困难;(2)组织学观察:随着时间的推移,塞来昔布组及布洛芬组肌腱与腱周组织之间间隙逐渐清楚,成熟纤维细胞逐渐排列规则且方向一致;而生理盐水组肌腱与腱周组织之间也逐渐有间隙,但成纤维细胞较多且排列不规则;(3)生物力学测定:①肌腱滑动阻力测定:术后4、8周时,塞来昔布组、布洛芬组与生理盐水组肌腱滑动阻力比较,其差异均有统计学意义(0.354 ±0.078/0.382 ±0.121 vs 0.521 ±0.126,P<0.05;0.075±0.035/0.097±0.043 vs0.414 ±0.110,P<0.01);②肌腱最大拉伸断裂强度:术后4、8周时塞来昔布组、生理盐水组与布洛芬组肌腱最大拉伸断裂强度比较,其差异均有统计学意义(36.812 ±6.388 vs 24.899±4.667,P<0.05;34.297±8.132 vs 24.899±4.667,P<0.01; 54.515±4.688/59.037±6.606 vs 42.418±5.594,P<0.01).结论 塞来昔布能有效预防肌腱粘连,且不影响肌腱愈合.%Objective To explore the effect of celecoxib on the tendon adhesion and healing after anastomosis.Methods 54 New Zealand white rabbits were randomly assigned to one of 3 ( celecoxib,ibuprofen,and saline) groups.The deep flexor tendon was transected,followed by a primary repair.The care was begun the day after surgery and was continually provided for 14 days.Celecoxib was given[20 mg/( kg · d

  12. Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Sakane, K.K. [Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, São José dos Campos, SP (Brazil); Monteiro, C.J.; Silva, W.; Silva, A.R. [Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG (Brazil); Santos, P.M. [Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, São José dos Campos, SP (Brazil); Lima, K.F. [Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG (Brazil); Moraes, K.C.M. [Instituto de Biociências, Departamento de Biologia, Universidade Estadual Paulista ‘‘Júlio de Mesquita Filho’’, Rio Claro, SP (Brazil)

    2013-11-29

    Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.

  13. EFFECTS OF p53 GENE THERAPY COMBINED WITH CYCLOOXYGENASE-2 INHIBITOR ON CYCLOOXYGENASE-2 GENE EXPRESSION AND GROWTH INHIBITION OF HUMAN LUNG CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    WANG Zhao-Xia; LU Bin-Bin; WANG Teng; YIN Yong-Mei; DE Wei; SHU Yong-Qian

    2007-01-01

    Background Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro, in animal models, and in human clinical trials. The antitumor effect of selective cyclooxygenase (COX)-2 inhibitors has been demonstrated in preclinical studies. However, no information is available on the effects of p53 gene therapy combined with selective COX-2 inhibitor on COX-2 gene expression and growth inhibition of human lung cancer cells. Methods We evaluated the effects of recombinant adenovirus-p53 (Ad-p53) gene therapy combined with selective COX-2 inhibitor on the proliferation, apoptosis, cell cycle arrest of human lung adenocarcinoma A549 cell line, and the effects of tumor suppressor exogenous wild type p53 on COX-2 gene expression. Results Ad-p53 gene therapy combined with selective COX-2 inhibitor celecoxib shows significant synergistic inhibition effects on the growth of human lung adenocarcinoma A549 cell line. Exogenous p53 gene can suppress COX-2 gene expression. Conclusions Significant synergistic inhibition effects of A549 cell line by the combined Ad-p53 and selective COX-2 inhibitor celecoxib may be achieved by enhancement of growth inhibition, apoptosis induction and suppression of COX-2 gene expression. This study provides first evidence that the administration of p53 gene therapy in combination with COX-2 inhibitors might be a new clinical strategy for the treatment or prevention of NSCLC.

  14. Helicobacter pylori vacuolating toxin A and apoptosis

    Directory of Open Access Journals (Sweden)

    Rassow Joachim

    2011-11-01

    Full Text Available Abstract VacA, the vacuolating cytotoxin A of Helicobacter pylori, induces apoptosis in epithelial cells of the gastic mucosa and in leukocytes. VacA is released by the bacteria as a protein of 88 kDa. At the outer surface of host cells, it binds to the sphingomyelin of lipid rafts. At least partially, binding to the cells is facilitated by different receptor proteins. VacA is internalized by a clathrin-independent mechanism and initially accumulates in GPI-anchored proteins-enriched early endosomal compartments. Together with early endosomes, VacA is distributed inside the cells. Most of the VacA is eventually contained in the membranes of vacuoles. VacA assembles in hexameric oligomers forming an anion channel of low conductivity with a preference for chloride ions. In parallel, a significant fraction of VacA can be transferred from endosomes to mitochondria in a process involving direct endosome-mitochondria juxtaposition. Inside the mitochondria, VacA accumulates in the mitochondrial inner membrane, probably forming similar chloride channels as observed in the vacuoles. Import into mitochondria is mediated by the hydrophobic N-terminus of VacA. Apoptosis is triggered by loss of the mitochondrial membrane potential, recruitment of Bax and Bak, and release of cytochrome c.

  15. Metalloregulation of Helicobacter pylori physiology and pathogenesis

    Directory of Open Access Journals (Sweden)

    Jennifer Angeline Gaddy

    2015-09-01

    Full Text Available Helicobacter pylori is a Gram-negative spiral-shaped bacterium that colonizes over half of the world’s population. Chronic H. pylori infection is associated with increased risk for numerous disease outcomes including gastritis, dysplasia, neoplasia, B-cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma, and invasive adenocarcinoma. The complex interactions that occur between pathogen and host are dynamic and exquisitely regulated, and the relationship between the H. pylori and its human host are no exception. To successfully colonize, and subsequently persist, within the human stomach H. pylori must temporally regulate numerous genes to ensure localization to the gastric lumen and coordinated expression of virulence factors to subvert the host’s innate and adaptive immune response. H. pylori achieves this precise gene regulation by sensing subtle environmental changes including host-mediated alterations in nutrient availability and responding with dramatic global changes in gene expression. Recent studies revealed that the presence or absence of numerous metal ions encountered in the lumen of the stomach, or within host tissues, including nickel, iron, copper and zinc, can influence regulatory networks to alter gene expression in H. pylori. These expression changes modulate the deployment of bacterial virulence factors that can ultimately influence disease outcome. In this review we will discuss the environmental stimuli that are detected by H. pylori as well as the trans regulatory elements, specifically the transcription regulators and transcription factors, that allow for these significant transcriptional shifts.

  16. Helicobacter pylori: From Infection to Cure

    Directory of Open Access Journals (Sweden)

    ABR Thomson

    1996-01-01

    Full Text Available Over 380 abstracts, presentations and posters of recent advances were highlighted at the European and International Helicobacter pylori meeting held July 7 to 9, 1995 in Edinburgh, Scotland. New advances abound, with major interest focusing on the simple, safe, inexpensive new `gold standard’ for H pylori eradication therapy: a single week of tid omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg, or omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg. To avoid false negative results, two biopsies must be taken from the antrum and two from the gastric body at least four weeks after completion of eradication therapy, and ideally should be supplemented with at least one further H pylori test such as a biopsy for urease activity or culture, or a urea breath test. While most patients with a gastric or duodenal ulcer (DU who do not consume nonsteroidal anti-inflammatory drugs are infected with H pylori, the association is much less apparent in those with a DU who present with an upper gastrointestinal hemorrhage. H pylori eradication for nonulcer dyspepsia is not widely recommended, and the patient with a DU given effective H pylori eradication who presents with dyspepsia likely has erosive esophagitis rather than recurrent DU or H pylori. Gastroenterologists are at increased risk of H pylori infection, particularly older gastroenterologists who are very busy endoscopists.

  17. Helicobacter pylori eradication for preventing gastric cancer.

    Science.gov (United States)

    Lu, Bin; Li, Meng

    2014-05-21

    Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer (GC) development, which is one of the most challenging malignant diseases worldwide with limited treatments. In the multistep pathogenesis of GC, H. pylori infection slowly induces chronic active gastritis, which progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia, and dysplasia, and then finally to GC. Although eradication of H. pylori is a reasonable approach for the prevention of GC, there have been some contradictory reports, with only some long-term follow-up data showing efficacy of this approach. The inconsistencies are likely due to the insufficient number of participants, relatively short follow-up periods, poor quality of study designs, and the degree and extent of preneoplastic changes at the time of H. pylori eradication. This review analyzes recent high-quality studies to resolve the discrepancies regarding the eradication of H. pylori for GC prevention. The relationship between H. pylori eradication and GC/precancerous lesions/metachronous GC is examined, and the cost-effectiveness of this strategy in the prevention of GC is assessed. Although it is assumed that eradication of H. pylori has the potential to prevent GC, the feasibility and appropriate timing of this strategy for cancer prevention remain to be determined. As a result, additional well-designed trials with longer follow-up periods are needed to clarify this issue.

  18. Helicobacter Pylori Seropostivity of Colon Cancer

    Directory of Open Access Journals (Sweden)

    F. Tugba Kos

    2014-03-01

    Full Text Available Aim: Until now many researches have showed that Helicobacter pylori infection may be etiological factor of colorectal cancer. The aim of current study was to investigate the frequency of H.pylori infection seropositivity of colorectal cancer patients and compare the clinicopathological features of H.pylori positive patients with negative ones. Material and Method: Seventy four colorectal patients were included in study. Retrospectively, patients clinical features, surgery history and pathological characteristics were screened. Patients group serum samples were collected. H.pylori Ig G level were quantitatively measured with ELISA method and levels above 5 arbU/ml were accepted as seropositive. Results: Patients median age was 60.5 ( range 26-83 and 56.8% (n=42 were male. H.pylori Ig G was positive in 37.8% (n=28 and negative in 62.2% (n=46 of patient group. H.pylori serpositive and negative patients median age of diagnosis were 56 and 64 respectively (p=0.01. There were no significant difference between H.pylori seropositive group when compared with negative group according to age, level of CEA and Ca 19-9, stage, lymph node involvement, perineural and vascular invasion, presence of polyps, differantion, localisation of tumours. Discussion: H.pylori seropositive patients were diagnosed at younger age. Association of this finding with etiology was confusing. Further studies with healthy controls may provide detailed information about whether H.pylori seropositivity is associated with colorectal cancer etiology.

  19. Helicobacter Pylori and Gastric Cancer: Clinical Aspects

    Directory of Open Access Journals (Sweden)

    Zhi-Qiang Song

    2015-01-01

    Full Text Available Objective: Although Helicobacter pylori (H. pylori is considered as the main etiological factor for gastric cancer, the strategy of screening and treating the oncogenic bacterium is still controversial. The objective was to evaluate the status and progress of the cognition about the relationship between H. pylori infection and gastric cancer from a clinical aspect. Data Sources: The data used in this review were mainly from the PubMed articles published in English from 1984 to 2015. Study Selection: Clinical research articles were selected mainly according to their level of relevance to this topic. Results: Gastric cancer is the fifth most common malignancy and the third leading cause of cancer deaths worldwide. The main etiological factor for gastric cancer is H. pylori infection. About 74.7-89.0% gastric cancer was related to H. pylori infection. Up to date, some regional gastric cancer prevention programs including the detection and treatment of H. pylori infection are under way. Current data obtained from the randomized controlled trials suggest that population-based H. pylori screening and treatment is feasible and cost-effective in preventing gastric cancer; however, a population-based H. pylori eradication campaign would potentially lead to bacterial resistance to the corresponding antibiotics, as well as a negative impact on the normal flora. Conclusions: The important questions of feasibility, program costs, appropriate target groups for intervention, and the potential harm of mass therapy with antibiotics must first be answered before implementing any large-scale program.

  20. Helicobacter pylori: prospettive per un vaccino

    Directory of Open Access Journals (Sweden)

    Giuseppe Del Giudice

    2003-09-01

    Full Text Available Helicobacter pylori causes one of the most widespread infections worldwide: it affects more than 50% of the human population, and is responsible for serious gastric pathologies such as chronic gastritis, peptic ulcer, atrophic gastritis and, in some individuals, gastric cancer. Current treatments with antibiotics are efficacious, but encounters several drawbacks at the level of compliance, side effects, antibiotic resistance, etc.The availability of vaccines could contribute in reducing the burden of H. pylori associated diseases. Several bacterial antigens have been identified as virulence factors and proposed as potential vaccine candidates. Some of these antigens have been tested in experimental animal models of challenge with H. pylori. The experiments in animals have shown that prophylactic and therapeutic vaccination against H. pylori is indeed feasible. Several open questions still remain concerning the understanding of the host-microbe relationship and the quality of the immune response which should be induced in order to confer protective immunity in man.The answers to these questions will be crucial in helping the preparation of appropriate vaccine formulations able to efficaciously protect humans both prophylactically and therapeutically. A few clinical trials have been carried out so far with still limited results. Other trials in humans are in progress and are planned for the next few years.The final hope is that these new vaccines will show the expected efficacy against H. pylori and will permit the elimination of this pathogen which has cohabited with humans for more than 100,000 years.

  1. Clinical practice: Helicobacter pylori infection in childhood.

    Science.gov (United States)

    Ertem, Deniz

    2013-11-01

    Helicobacter pylori infection is recognised as a cause of gastritis and peptic ulcer disease (PUD) and usually acquired during the first years of life. While there is a decline in the prevalence of H. pylori infection in northern and western European countries, the infection is still common in southern and eastern parts of Europe and Asia. Symptoms of H. pylori-related PUD are nonspecific in children and may include epigastric pain, nausea and/or vomiting, anorexia, iron deficiency anaemia and hematemesis. Besides, only a small proportion of children develop symptoms and clinically relevant gastrointestinal disease. H. pylori infection can be diagnosed either by invasive tests requiring endoscopy and biopsy or non-invasive tests including the (13)C-urea breath test, detection of H. pylori antigen in stool and detection of antibodies in serum, urine and saliva. The aim of treatment is at least 90 % eradication rate of the bacteria, and a combination of two antibiotics plus a proton pump inhibitor has been recommended as first-line treatment. However, frequent use of antibiotics during childhood is associated with a decline in eradication rates and the search for new treatment strategies as well. This is an overview of the latest knowledge and evidence-based guidelines regarding clinical presentation, diagnosis and treatment of H. pylori infection in childhood. PMID:23015042

  2. Rescue Therapy for Helicobacter pylori Infection 2012

    Directory of Open Access Journals (Sweden)

    Javier P. Gisbert

    2012-01-01

    Full Text Available Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After 30 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has still to be found. Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face treatment failures. In designing a treatment strategy, we should not only focus on the results of primary therapy alone but also on the final—overall—eradication rate. The choice of a “rescue” treatment depends on which treatment is used initially. If a first-line clarithromycin-based regimen was used, a second-line metronidazole-based treatment (quadruple therapy may be used afterwards, and then a levofloxacin-based combination would be a third-line “rescue” option. Alternatively, it has recently been suggested that levofloxacin-based “rescue” therapy constitutes an encouraging 2nd-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, quadruple regimen may be reserved as a 3rd-line “rescue” option. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several “rescue” therapies are consecutively given.

  3. Helicobacter pyloriinfection and respiratory diseases: a review

    Institute of Scientific and Technical Information of China (English)

    Anastasios Roussos; Nikiforos Philippou; Konstantinos I Gouraoulianis

    2003-01-01

    In the past few years, a variety of extradigestive disorders,including cardiovascular, skin, rheumatic and liver diseases,have been associated with Helicobacter pylori(H. pylori)infection. The activation of inflammatory mediators by H. pyloriseems to be the pathogenetic mechanism underlying theobserved associations. The present review summarizes thecurrent literature, including our own studies, concerning theassociation between H. pvloriinfection and respiratory diseases.A small number of epidemiological and serologic, case-control studies suggest that H. pyloriinfection may beassociated with the development of chronic bronchitis. Afrequent coexistence of pulmonary tuberculosis and H. pyloriinfection has also been found. Moreover, recent studies haveshown an increasedH. pyloriseroprevalence in patients withbronchiectasis and in those with lung cancer. On the otherhand, bronchial asthma seems not to be related withH. pyloriinfection.All associations between H. pyloriinfection and respiratorydiseases are primarily based on case-control studies,concerning relatively small numbers of patients. Moreover,there is a lack of studies focused on the pathogenetic linkbetween respiratory diseases and H. pylori infection.Therefore, we believe that larger studies should beundertaken to confirm the observed results and to clarifythe underlying pathogenetic mechanisms.

  4. Detection of Helicobacter pylori in Nasal Polyps.

    Science.gov (United States)

    Bansal, Divya; Sharma, Sonal; Agarwal, Sarla; Saha, Rumpa; Gupta, Neelima

    2016-09-01

    To detect the presence of Helicobacter pylori in nasal polyps. A case-control study was conducted enrolling 35 patients with nasal polyps (cases) and patients undergoing septoplasty (controls). Fresh tissue samples were used for urea broth test and imprint cytology, while formalin fixed tissue sections were used for morphology, special stains and immunohistochemistry for H. pylori. Fresh stool samples from both groups were tested to correlate the gastrointestinal status. H. pylori was detected in 40.0 % (14/35) of cases and 8.5 % of controls (3/35) (p = 0.004) by immunohistochemistry. Amongst cases, eight were positive with urea broth test, six with imprint cytology (Giemsa stain), three with H & E, and nine with modified McMullen's stain. Hyperplasia of the lining epithelium and lymphoid aggregates were significantly noticed in nasal polyps positive for H. pylori. Stool antigen test was positive in subjects who were positive for H. pylori in the nasal mucosa. There appears to be an association between H. pylori and nasal polyps. Immunohistochemistry is more sensitive and specific method to detect H. pylori. H. pylori induced inflammatory tissue reaction pattern indicates a possible causal association. Further studies are needed to prove the causal relationship between H. pylori and nasal polyps. PMID:26830396

  5. Paediatric halitosis and helicobacter pylori infection

    International Nuclear Information System (INIS)

    To compare the presence of Helicobacter pylori (H. pylori) infection by stool antigen test in children with and without halitosis. Study Design: Comparative study. Place and Duration of Study: Department of Paediatrics, Fatih University Hospital, Ankara, Turkey, between December 2008 and June 2009. Methodology: Fifty-three patients aged between 3-15 years who presented to paediatrics outpatient clinic with halitosis and 55 healthy children aged between 4-15 years without halitosis were included in the study. Halitosis was confirmed with organoleptic test. Stool antigen test was performed in both groups. Inter group proportions were compared using chi square and Fisher exact tests with significance at p 0.05). Two weeks eradication treatment was administered to 11 patients with H. pylori infection and halitosis. After treatment, the symptoms of 8 patients with halitosis (72.7%) completely resolved and persisted in 3 patients (27.3%). Seven of the 11 patients who were administered eradication treatment also had abdominal pain along with halitosis. Both symptoms completely resolved in all those patients after treatment. Conclusion: Although no statistically significant difference existed between the rate of H. pylori infections among those with and without halitosis. Eradication treatment was found beneficial in the treatment of children with halitosis and positive H. pylori stool antigen test. (author)

  6. Treatment of Helicobacter Pylori in Children

    Directory of Open Access Journals (Sweden)

    F Famouri

    2014-04-01

    Full Text Available Childrenwith Helicobacter infection need treatment. The aim of treatment is elimination of H.Pylori. Most patients with this infection are asymptomatic and without peptic disease. Treatment and management of these patients are controversy. Conventional Treatment: The best treatment for H. pylori eradication regimens should have cure rates of at least 80%, be without major side effects, and induce minimal bacterial resistance. Antibiotics alone have not achieved this. Luminal acidity influences both the effectiveness of some antimicrobial agents and the survival of the bacteri; thus antibiotics have been combined with acid suppression such as proton pump inhibitors (PPIs, bismuth, or H2 antagonists. The “classic” regimen is treatment twice daily for 7 days with a PPI and clarithromycin plus either amoxicillin or metronidazole Bismuth has been used in the treatment of peptic ulcer disease and 1 part o quadruple therapy for H.Pylori but compliance of children for it is low.   Sequential Therapy  Sequential therapyinvolves dual therapy with a PPI and amoxicillin for 5 days followed sequentially by clarithromycin, Tinidazole and omeperazole for 5 days or other triple therapy for 7 days. This treatment has had 97% efficacy.   Adjunctive Therapies A number of studies have showed the potential benefits of probiotic therapy in H. pylori treatment regimens.Consumption of these drugs accompanied with other medications increase H.Pylori eradication.    

  7. Treatment of Helicobacter pylori Infection 2013.

    LENUS (Irish Health Repository)

    O'Connor, Anthony

    2013-09-01

    This review summarizes important studies regarding Helicobacter pylori therapy published from April 2012 up to March 2013. To begin with, the updated European Consensus Guidelines were published last year, highlighting the role of bismuth and nonbismuth quadruple regimen as first-line treatments. Cure rates for standard triple therapy remain acceptable in quite a few settings nowadays, and some reports on innovative triple therapies look promising. One study evaluating bismuth quadruple therapy as first-line therapy was reported. Regarding nonbismuth quadruple regimens, there is a trend of superiority emerging for the "concomitant" therapy over the "sequential" regimen. "Hybrid" therapy, a combination of sequential and concomitant therapy, has also shown advantage over sequential therapy. Levofloxacin-based therapies appear to be useful and versatile in second- and third-line therapies, with interesting results for newer generation quinolones, which may partially overcome antibiotic resistance. Some promising works have been reported for bismuth-based rescue therapy, using individualized therapies upon antimicrobial information, as well as for rifabutin fourth-line therapy. Probiotics appear to have an effect in terms of reducing side effects and improving compliance, but data on improvement of eradication rates remain controversial.

  8. Diagnosis and epidemiology of Helicobacter pylori infection.

    Science.gov (United States)

    Calvet, Xavier; Ramírez Lázaro, María-José; Lehours, Philippe; Mégraud, Francis

    2013-09-01

    A limited amount of new information was published in the field of diagnosis and epidemiology of Helicobacter pylori this last year. Besides some improvement in current tests, it is interesting to note the attempts to identify severe disease, for example gastric cancer, by breath analysis using nanomaterial-based sensors. In contrast, the predictive value for gastric cancer and atrophy of pepsinogen determinations was found inadequate. Prevalence studies of H. pylori infection have been carried out in adults and children around the world in the general population but also in specific communities. The usual risk factors were found. In addition, a Japanese study highlighted the role of grandmothers in the familial transmission of H. pylori. A study showed that the infection may not always readily establish itself in children, given the number of transient infections observed. It was also noted that after eradication, a first-year relapse is likely to be a recurrence of the previous infection, while later on it is probably a reinfection with a new strain.

  9. Treatment of Helicobacter pylori infection 2010.

    LENUS (Irish Health Repository)

    O'Connor, Anthony

    2012-02-01

    It is accepted that the success of Helicobacter pylori eradication treatment using standard triple therapy is declining. Resistance, particularly to clarithromycin, has been shown in numerous countries to be rising to a level where the use of standard triple therapy in its current form may no longer be justified. The two major factors influencing resistance are prior exposure to the antibiotic and compliance with therapy. Regimes based on bismuth and levofloxacin, which had previously been mainly second-line options, are now emerging as superior first-line options. Trials of sequential and concomitant therapies are also showing the usefulness of these treatments in different populations. Options for third and subsequent line therapies include furazolidone and rifabutin-based regimes. Susceptibility testing should be performed to maintain accurate data on resistance levels, and has also clinical utility in difficult to eradicate cases. None of these, however, will be successful unless compliance is improved upon. If compliance is assured and eradication confirmation pursued, it has been repeatedly illustrated that near full eradication is achievable.

  10. Study of serum Helicobacter pylori soluble antigen

    Institute of Scientific and Technical Information of China (English)

    吴勤动; 朱永良

    2002-01-01

    Objective:to explore a new serological method for detecting Helicobacter pylori(H.pylori) infection.Methods:Serum soluble antigen of H.pylori was detected by using avidin-biotin ELISA technique to evaluate the status of H.pylori infection and for comparison with rapid urease test(RUT).histologic examination and serology,Results:The sensitivity,specificity,positive predictive value and negative predictive value were 77.46% ,91.07%,91.67% and 76.12%,respectively.The prevalence rate of werum H. pylori soluble antigen in 138 patients undergong endoscopy was similar to the rate obtained by 14 C-UBT methods(P>0.05).Conclusions:The detection of serum H.pylori soluble antigen(HpSAg) could be used as a new serological method which is accurate,and convenient,not affected by the memorizing raction of serum antibody;is more sensitive,more specific and suitable for dinical diagriosis,and evaluation of eradication and for follow-up of H.pylori as well as for detection in children and pregnant women.

  11. Gastric angiogenesis and Helicobacter pylori infection Angiogénesis gástrica e infección por Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    I. D. Pousa

    2006-06-01

    Full Text Available The formation of new blood vessels seen in conditions commonly associated with Helicobacter pylori (H. pylori infection, including gastritis, peptic ulcer, and gastric carcinoma, prompts consideration of a potential relationship between mucosal colonization by this organism and the angiogenic process. H. pylori directly or indirectly damages endothelial cells, which induces a number of changes in the microvasculature of the gastric mucosa. In H. pylori-associated conditions, that is, in gastritis, peptic ulcer and gastric carcinoma, there is an increased concentration of angiogenic factors, and subsequently a formation of new blood vessels. However, this early angiogenesis -which is activated to repair the gastric mucosa- is subsequently inhibited in patients with peptic ulcer, and ulcer healing is thus delayed. This may be due to the antiproliferative action of this organism on endothelial cells. While the angiogenic process becomes inhibited in infected patients with peptic ulcer, it remains seemingly active in those with gastritis or gastric cancer. This fact is in support of the notion suggested by various studies that peptic ulcer and gastric cancer are mutually excluding conditions. In the case of gastric cancer, neoangiogenesis would enhance nutrient and oxygen supply to cancer cells, and thus tumor growth and metastatic spread.

  12. Efficacy and Safety of Zhuanggu Joint Capsules in Combination with Celecoxib in Knee Osteoarthritis: A Multi-center, Randomized, Double-blind, Double-dummy, and Parallel Controlled Trial

    Institute of Scientific and Technical Information of China (English)

    Xian-Long Zhang; Jing Yang; Liu Yang; Jian-Guo Liu; Xin-Yu Cai; Wei-Ming Fan; Xue-Qing Yun

    2016-01-01

    Background:Knee osteoarthritis (KOA) is a chronic joint disease that manifests as knee pain as well as different degrees of lower limb swelling,stiffness,and movement disorders.The therapeutic goal is to alleviate or eliminate pain,correct deformities,improve or restore joint functions,and improve the quality of life.This study aimed to evaluate the efficacy and safety of Zhuanggu joint capsules combined with celecoxib and the benefit of treatment with Zhuanggu alone for KOA.Methods:This multi-center,randomized,double-blind,double-dummy,parallel controlled trial,started from December 2011 to May 2014,was carried out in 6 cities,including Beijing,Shanghai,Chongqing,Changchun,Chengdu,and Nanjing.A total of 432 patients with KOA were divided into three groups (144 cases in each group).The groups were treated,respectively,with Zhuanggu joint capsules combined with celecoxib capsule simulants,Zhuanggu joint capsules combined with celecoxib capsules,and celecoxib capsules combined with Zhuanggu joint capsule simulants for 4 weeks consecutively.The improvement of Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and the decreased rates in each dimension of WOMAC were evaluated before and after the treatment.Intergroup and intragroup comparisons of quantitative indices were performed.Statistically significant differences were evaluated with pairwise comparisons using Chi-square test (or Fisher's exact test) and an inspection level ofα =0.0167.Results:Four weeks after treatment,the total efficacies of Zhuanggu group,combination group,and celecoxib group were 65%,80%,and 64%,respectively,with statistically significant differences among the three groups (P =0.005).Intergroup pairwise comparisons showed that the total efficacy of the combination group was significantly higher than that of the Zhuanggu (P =0.005) and celecoxib (P =0.003)groups.The difference between the latter two groups was not statistically significant (P > 0.0167).Four weeks

  13. A cultured strain of "Helicobacter heilmannii," a human gastric pathogen, identified as H-bizzozeronii: Evidence for zoonotic potential of Helicobacter

    DEFF Research Database (Denmark)

    Jalava, K.; On, Stephen L.W.; Harrington, Clare S.;

    2001-01-01

    We compared the characteristics of a cultured human "Helicobacter heilmannii" isolate with those of other helicobacters found in animals. Phenotypic, protein profile, 16S rDNA sequence, and DNA-DNA hybridization analyses identified the human strain as H. bizzozeronii, a species frequently found...... in dogs. Thus, H. bizzozeronii may have zoonotic potential....

  14. Inhibitory effect of polaprezinc on the inflammatory response to Helicobacter pylori.

    Science.gov (United States)

    Handa, Osamu; Yoshida, Norimasa; Tanaka, Yukiko; Ueda, Miho; Ishikawa, Takeshi; Takagi, Tomohisa; Matsumoto, Naoyuki; Naito, Yuji; Yoshikawa, Toshikazu

    2002-11-01

    Helicobacter pylori-infected gastrointestinal mucosa is frequently infiltrated by polymorphonuclear leukocytes (PMN) and monocytes, and these invading cells have been implicated in gastrointestinal mucosal inflammation. To clarify the efficacy of polaprezinc, a chelate compound consisting of zinc and L-carnosine, against H pylori-induced inflammation including PMN infiltration, the in vitro effects of this drug on interleukin (IL)-8 production by an established gastric cancer cell line (MKN 45 cells) and on PMN-endothelial cell adhesive interactions was investigated. Polaprezinc and zinc sulphate inhibited IL-8 production by MKN 45 cells in response to stimulation with H pylori water extract (HPE) in a dose-dependent manner from 10(-7) M to 10(-5) M. In addition, the expression of CD11b and CD18 on PMN and PMN-dependent adhesion to endothelial cells elicited by HPE was inhibited by polaprezinc and zinc sulphate in a concentration-dependent manner. L-carnosine did not have any effects on IL-8 production or PMN-endothelial cell interactions. These results suggest that polaprezinc, mainly the zinc component, may inhibit H pylori-induced PMN-mediated gastric inflammation by attenuating CD11b/CD18 expression on PMN and IL-8 production from gastric epithelial cells. PMID:12464972

  15. Antiadhesive Properties of Arabinogalactan Protein from Ribes nigrum Seeds against Bacterial Adhesion of Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Jutta Messing

    2014-03-01

    Full Text Available Fruit extracts from black currants (Ribes nigrum L. are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. For detailed investigations an arabinogalactan protein (F2 was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. Bacterial adhesins affected were identified by overlay assay with immobilized ligands. 125I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. F2 inhibited the binding of BabA and fibronectin-binding adhesin to its specific ligands. Radiolabeled F2 bound non-specifically to different strains of H. pylori; and to BabA deficient mutant. F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. From these data the non-specific interactions between F2 and the H. pylori lead to moderate antiadhesive effects.

  16. Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori.

    Science.gov (United States)

    Messing, Jutta; Niehues, Michael; Shevtsova, Anna; Borén, Thomas; Hensel, Andreas

    2014-01-01

    Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. Bacterial adhesins affected were identified by overlay assay with immobilized ligands. ¹²⁵I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. F2 inhibited the binding of BabA and fibronectin-binding adhesin to its specific ligands. Radiolabeled F2 bound non-specifically to different strains of H. pylori; and to BabA deficient mutant. F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. From these data the non-specific interactions between F2 and the H. pylori lead to moderate antiadhesive effects. PMID:24662083

  17. Bactericidal and anti-adhesive properties of culinary and medicinal plants against Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Rachel O'Mahony; Huda Al-Khtheeri; Deepeka Weerasekera; Neluka Fernando; Dino Vaira; John Holton; Christelle Basset

    2005-01-01

    AIM: To investigate the bactericidal and anti-adhesive properties of 25 plants against Helicobacter pylori (H pylori).METHODS: Twenty-five plants were boiled in water to produce aqueous extracts that simulate the effect of cooking. The bactericidal activity of the extracts was assessed by a standard kill-curve with seven strains of H pylori. The anti-adhesive property was assessed by the inhibition of binding of four strains of FITC-labeled H pylori to stomach sections. RESULTS: Of all the plants tested, eight plants, including Bengal quince, nightshade, garlic, dill, black pepper, coriander, fenugreek and black tea, were found to have no bactericidal effect on any of the isolates. Columbo weed, long pepper, parsley, tarragon, nutmeg, yellow-berried nightshade, threadstem carpetweed, sage and cinnamon had bactericidal activities against H pylori, but total inhibition of growth was not achieved in this study. Among the plants that killed H pylori, turmeric was the most efficient, followed by cumin, ginger, chilli, borage, black caraway, oregano and liquorice. Moreover, extracts of turmeric; borage and parsley were able to inhibit the adhesion of H pylori strains to the stomach sections.CONCLUSION: Several plants that were tested in our study had bactericidal and/or anti-adhesive effects on H pylori. Ingestion of the plants with anti-adhesive properties could therefore provide a potent alternative therapy for H pylori infection, which overcomes the problem of resistance associated with current antibiotic treatment.

  18. Helicobacter canis bacteremia in a renal transplant patient

    NARCIS (Netherlands)

    van der Vusse, M. L.; van Son, W. J.; Ott, A.; Manson, W.

    2014-01-01

    Here we present a case report of a 41-year-old woman suffering from high fever and bacteremia due to Helicobacter canis, 11months after kidney transplantation. Identification of H.canis was achieved by 16s rDNA sequence analysis of a positive blood culture. The patient was restored fully to health a

  19. Molecular Mechanisms of Antibiotic Resistance in Helicobacter pylori

    NARCIS (Netherlands)

    M.M. Gerrits (Monique)

    2004-01-01

    textabstractAn estimated 4 to 5 million individuals in the Netherlands are actively infected with Helicobacter pylori. Eradication of this bacterium becomes more difficult as the prevalence of antibiotic resistance is increasing worldwide. Most H. pylori infections are now diagnosed by non-invasi

  20. Relationship of Halitosis with Gastric Helicobacter Pylori Infection

    Directory of Open Access Journals (Sweden)

    Farnaz HajiFattahi

    2015-10-01

    Full Text Available Objectives: Gastric infection with Helicobacter pylori may be one of the main causes of halitosis. This study was performed to evaluate the relationship of Heli- cobacter pylori infection with halitosis.Materials and Methods: This case control study was performed on 44 dyspeptic patients with a mean age of 34.29±13.71 years (range 17 to 76 years. The case group included 22 patients with halitosis and no signs of diabetes mellitus, renal or liver failure, upper respiratory tract infection, malignancies, deep carious teeth, severe  periodontitis,  coated  tongue,  dry  mouth  or poor  oral  hygiene.  Control group included 22 patients without halitosis and the same age, sex, systemic and oral conditions as the case group. Halitosis was evaluated using organoleptic test (OLT and Helicobacter pylori infection was evaluated by Rapid Urease Test (RUT during endoscopy. The data were statistically analyzed using chi square, Mann Whitney and t-tests.Results: Helicobacter pylori infection was detected in 20 (91% out of 22 halitosis patients, and 7 control subjects (32% (P<0.001.Conclusion: Helicobacter pylori gastric infection can be a cause of bad breath. Dentists should pay more attention to this infection and refer these patients to in- ternists to prevent further gastrointestinal (GI complications and probable malig- nancies.

  1. Association between helicobacter pylori and gastrointestinal symptoms in children

    NARCIS (Netherlands)

    Spee, Leo A A; Madderom, Marieke B; Pijpers, Maaike; van Leeuwen, Yvonne; Berger, Marjolein Y

    2010-01-01

    OBJECTIVE: Recurrent abdominal pain (RAP) and other gastrointestinal (GI) symptoms are common complaints among children. The role of Helicobacter pylori in the cause of these complaints remains controversial. Nevertheless, there is an increasing pressure on primary care clinicians to screen for H py

  2. Assessment of Helicobacter pylori eredication in patients on NSAID treatment

    NARCIS (Netherlands)

    Vonkeman, Harald E.; Leest, de H.T.J.I.; Laar, van de M.A.F.J.; Baarlen, van J.; Steen, K.S.S.; Lems, W.F.; Bijlsma, J.W.J.; Kuipers, E.J.; Houben, H.H.M.L.; Janssen, M.; Dijkmans, B.A.C.

    2012-01-01

    Background: In this post-hoc analysis of a randomized, double blind, placebo controlled trial, we measured the sensitivity and specificity of Helicobacter pylori IgG-antibody titer changes, hematoxylin and eosin (H&E) stains, immunohistochemical (IHC) stains and culture results in NSAID using patien

  3. Assessment of Helicobacter pylori eradication in patients on NSAID treatment

    NARCIS (Netherlands)

    H.E. Vonkeman (Harald); H.T.J.I. de Leest; M.A.F.J. van de Laar (Martin); J. Van Baarlen; K.S.S. Steen (K. S S); W.F. Lems (Willem); J.W.J. Bijlsma (Hans); E.J. Kuipers (Ernst); H.H.M.L. Houben (Harry); M. Janssen (Matthijs); B.A.C. Dijkmans (Ben)

    2012-01-01

    textabstractBackground: In this post-hoc analysis of a randomized, double blind, placebo controlled trial, we measured the sensitivity and specificity of Helicobacter pylori IgG-antibody titer changes, hematoxylin and eosin (H&E) stains, immunohistochemical (IHC) stains and culture results in NSAID

  4. Antibacterial Effects of Grape Extracts on Helicobacter pylori▿

    OpenAIRE

    Brown, Joseph C.; Huang, Guohui; Haley-Zitlin, Vivian; Jiang, Xiuping

    2008-01-01

    Anti-Helicobacter pylori activities were determined by agar dilution, confocal laser scanning microscopy, and cell proliferation assays following treatment with various grape extracts. Muscadine grape skin possessed the strongest activity, followed by grape synergy (skin and seed) and seed, suggesting that higher phenolic levels do not necessarily determine overall anti-H. pylori efficacy.

  5. Improving Compliance with Helicobacter Pylori Eradication Therapy: When and How?

    OpenAIRE

    O'Connor, John P. Anthony; Taneike, Ikue; O'Morain, Colm

    2009-01-01

    Compliance with therapy is the single most important factor in Helicobacter pylori (H. pylori) eradication. Poorer levels of compliance with therapy are associated with significantly lower levels of eradication. Numerous factors can contribute to achieving good levels of compliance. These include the complexity and duration of treatment. It is also important that the physicia...

  6. Is Helicobacter Pylori a Possible Etiopathogenic Factor in Chronic Tonsillitis?

    Directory of Open Access Journals (Sweden)

    Elmas Ozgun

    2014-03-01

    Full Text Available Aim: Helicobacter pylori is the major gastric pathogen which has an important role in the etiopathogenesis of chronic gastritis. We investigated the presence of Helicobacter pylori as an extragastric reservoir in the tonsillectomy specimens to display if it is an etiologic factor in the development of chronic tonsilitis. Material and Method: In the current study, 100 cases with chronic tonsilitis were examined in bilateral tonsillectomy specimens. The colonization of the microorganism have been evaluated with hematoxylin-eosin and giemsa stains under the light microscope.Results: Helicobacter pylori has been detected in 33 cases (33% on one side of the bilateral tonsillectomy specimens while it has been seen in 15 cases (15% on both sides which demonstrated positivity in 48 cases (48% in total. No colonization has been observed in the remaining 52 cases (52%. Discussion: Due to the considerable positivity in our study, the histopathologic evaluation of tonsillary Helicobacter pylori colonization may be instrumental in the etiologic association with chronic tonsillitis.

  7. Enhancement of Amoxicillin Resistance after Unsuccessful Helicobacter pylori Eradication▿

    OpenAIRE

    Nishizawa, Toshihiro; Suzuki, Hidekazu; Tsugawa, Hitoshi; Muraoka, Hiroe; Matsuzaki, Juntaro; Hirata, Kenro; Ikeda, Fumiaki; Takahashi, Masahiko; Hibi, Toshifumi

    2011-01-01

    A high rate of resistance (49.5 to 72.7%) to amoxicillin (AMX) was observed in Helicobacter pylori after two or three unsuccessful eradication attempts. Unsuccessful eradication regimens significantly increase resistance to not only clarithromycin (CLR) and metronidazole (MNZ) but also AMX.

  8. Effects of Helicobacter Pylori Eradication Among Adults with Intellectual Disability

    Science.gov (United States)

    Wallace, R. A.; Schluter, P. J.; Webb, P. M.

    2004-01-01

    Compared to the general population, Helicobacter pylori infection is more common among adults with intellectual disability (ID) and is associated with greater levels of disability, maladaptive behaviour, and institutionalization. Little information exists about the effects of eradication therapy in this group, so we aimed to evaluate: (1) success…

  9. SURVIVAL OF HELICOBACTER PYLORI IN A NATURAL FRESHWATER ENVIRONMENT

    Science.gov (United States)

    The mode by which Helicobacter pylori, the causative agent of most gastric ulcers, is transmitted remains undetermined. Epidemiological evidence suggests these organisms are waterborne; however, H. pylori has rarely been grown from potential water sources. This may be due to th...

  10. A METHOD TO DETECT VIABLE HELICOBACTER PYLORI BACTERIA IN GROUNDWATER

    Science.gov (United States)

    The inability to detect the presence of viable Helicobacter pylori bacteria in environmental waters has hindered the public health community in assessing the role water may playin the transmission of this pathogen. This work describes a cultural enrichment method coupled with an...

  11. Furazolidone therapy for Helicobacter pylori: Is it effective and safe?

    Institute of Scientific and Technical Information of China (English)

    Vincenzo De Francesco; Enzo Ierardi; Cesare Hassan; Angelo Zullo

    2009-01-01

    Some aspects related with the use of furazolidone as a rescue therapy for Helicobacter pylori ( H pylori) infection should be remarked, especially regarding its potential oncologic risk. The inclusion of furazolidone in a treatment regimen for H pylori infection is, at least, controversial, and it does not appear to be safe.

  12. OVERVIEW: DISINFECTION OF HELICOBACTER PYLORI AND AEROMONAS SPECIES

    Science.gov (United States)

    Helicobacter pylori and Aeromonas hydrophila are contaminants listed on the USEPA's 1998 Contaminant Candidate List (CCL).The sensitivity of H. pylori to chlorine and of Aeromonas spp. to inactivation by free chlorine, chloramine and ultraviolet (UV) was examined. Selective and...

  13. Inflammation, Immunity, and Vaccines for Helicobacter pylori Infection

    DEFF Research Database (Denmark)

    Walduck, Anna; Andersen, Leif P; Raghavan, Sukanya

    2015-01-01

    During the last year, a variety of studies have been published that increases our understanding of the basic mechanisms of immunity and inflammation in Helicobacter pylori infection and progression to gastric cancer. Innate immune regulation and epithelial cell response were covered by several...

  14. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Figueiredo, C.; Seruca, R.;

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair...

  15. Helicobacter pylori in childhood : aspects of prevalence, diagnosis and treatment

    NARCIS (Netherlands)

    Mourad-Baars, Petronella Elisabeth Cornelia

    2012-01-01

    In this dissertation we present the results of our research on Helicobacter pylori infections in childhood, focusing on the prevalence, diagnosis and treatment of the infection. Our studies were conducted in the Netherlands, Europe and Indonesia. We discuss diagnostic tests, therapeutic regimens, re

  16. Roles of the Peptide Transport Systems and Aminopeptidase PepA in Peptide Assimilation by Helicobacter pylori.

    Science.gov (United States)

    Ki, Mi Ran; Lee, Ji Hyun; Yun, Soon Kyu; Choi, Kyung Min; Hwang, Se Young

    2015-10-01

    Peptide assimilation in Helicobacter pylori necessitates a coordinated working of the peptide transport systems (PepTs) and aminopeptidase (PepA). We found that H. pylori hydrolyzes two detector peptides, L-phenylalanyl-L-3-thiaphenylalanine (PSP) and L-phenylalanyl-L-2- sulfanilylglycine (PSG), primarily before intake and excludes their antibacterial effects, whereas Escherichia coli readily transports them with resultant growth inhibition. PSP assimilation by H. pylori was inhibited by aminopeptidase inhibitor bestatin, but not by dialanine or cyanide-m-chlorophenylhydrazone, contrary to that of E. coli. RT- and qRT-PCR analyses showed that H. pylori may express first the PepTs (e.g., DppA and DppB) and then PepA. In addition, western blot analysis of PepA suggested that the bacterium secretes PepA in response to specific inducers.

  17. The Results of Helicobacter Pylori Eradication on Repeated Bleeding in Patients with Stomach Ulcer

    OpenAIRE

    Horvat, Darko; Včev, Aleksandar; Soldo˛, Ivan; Timarac, Jasna; Dmitrović, Branko; Mišević, Tonči; Ivezić, Zdravko; Kraljika, Nikola

    2005-01-01

    The triple therapy of Helicobacter pylori eradication prevents repeated bleeding from stomach ulcer. The aim of this one-way blind prospective study was to evaluate the efficiency of the two-week triple therapy for Helicobacter pylori eradication in preventing renewed bleeding in patients with stomach ulcer within one year. This research included 60 hospitalized patients with bleeding stomach ulcer and positive Helicobacter pylori infection, 34 men and 26 women (average age 59.7 years). The p...

  18. Survey of Helicobacter infection in domestic and feral cats in Korea

    OpenAIRE

    Ghil, Heh-Myung; Yoo, Jong-Hyeon; Jung, Woo-Sung; CHUNG, Tae-Ho; Youn, Hwa-Young; Hwang, Cheol-Yong

    2009-01-01

    Discovery of Helicobacter (H.) pylori has led to a fundamental change in our understanding of gastric diseases in humans. Previous studies have found various Helicobacter spp. in dogs and cats, and pets have been questioned as a zoonotic carrier. The present study surveyed the Helicobacter infections and investigated the presence of H. felis and H. pylori infections in domestic and feral cats in Korea. Sixty-four domestic cats and 101 feral cats were selected from an animal shelter. Saliva an...

  19. The presence of Helicobacter pylori in oral cavities of patients with leukoplakia and oral lichen planus

    OpenAIRE

    Magdalena Kazanowska-Dygdała; Irena Duś; Małgorzata Radwan-Oczko

    2016-01-01

    ABSTRACT Objective Helicobacter pylori infection is one of the most common bacterial infections in men. This gastrointestinal pathogen is closely related to gastritis, peptic ulcers, and the increased risk of gastric cancer. Numerous studies have indicated oral cavities as possible Helicobacter pylori reservoirs. Helicobacter pylori has been detected both in supragingival and subgingival plaques, and also in saliva. In addition, the relationship between lesions of oral mucosa and the presenc...

  20. The Efect of Helicobacter Pylori Eradication on Atrophic Gastritis and Intestinal metaplasia

    OpenAIRE

    Guldem Kilciler

    2011-01-01

     Aim: The aim of this prospective study was to evaluate whether helicobacter pylori eradication could improve gastric atropy or intestinal metaplasia. Material and Method: Forty-two pylori infected patients were evaluated for the status of atrophic gastritis and intestinal metaplasia. Two biopsy specimens from antrum and two biopsy specimens from corpus were taken before and 6 months after the helicobacter pylori eradication therapy. Helicobacter pylori status was determined by C-urea br...

  1. Gastric Helicobacters in domestic animals and nonhuman primates and their significance for human health

    OpenAIRE

    Haesebrouck, Freddy; Pasmans, Frank; Flahou, Bram; Chiers, Koen; Baele, Margo; Meyns, Tom; Decostere, Annemie; Ducatelle, Richard

    2009-01-01

    Summary: Helicobacters other than Helicobacter pylori have been associated with gastritis, gastric ulcers, and gastric mucosa-associated lymphoid tissue lymphoma in humans. These very fastidious microorganisms with a typical large spiral-shaped morphology were provisionally designated “H. heilmannii,” but in fact they comprise at least five different Helicobacter species, all of which are known to colonize the gastric mucosa of animals. H. suis, which has been isolated from the stomachs of pi...

  2. Helicobacter pylori antibiotic resistance in Iran

    Institute of Scientific and Technical Information of China (English)

    Marjan Mohammadi; Delaram Doroud; Nazanin Mohajerani; Sadegh Massarrat

    2005-01-01

    AIM: To examine the frequency of antibiotic resistance in Iranian Helicobacter pylori(H pylori) strains isolated from two major hospitals in Tehran.METHODS: Examination of antibiotic resistance was performed on 120 strains by modified disc diffusion test and PCR-RFLP methods. In addition, in order to identify the possible causes of the therapeutic failure in Iran, we also determined the resistance of these strains to the most commonly used antibiotics (metronidazole, amoxicillin,and tetracycline) by modified disc diffusion test.RESULTS: According to modified disc diffusion test, 1.6% of the studied strains were resistant to amoxicillin, 16.7% to clarithromycin, 57.5% to metronidazole, and there was no resistance to tetracycline. Of the clarithromycin resistant strains, 73.68% had the A2143G mutation in the 23S rRNA gene, 21.05% A2142C, and 5.26% A2142G.None of the sensitive strains were positive for any of the three point mutations. Of the metronidazole resistant strains, deletion in rdxA gene was studied and detected in only 6 (5%) of the antibiogram-based resistant strains.None of the metronidazole sensitive strains possessed rdxA gene deletion.CONCLUSION: These data show that despite the fact that clarithromycin has not yet been introduced to the Iranian drug market as a generic drug, nearly 20% rate of resistance alerts toward the frequency of macrolide resistance strains, which may be due to the widespread prescription of erythromycin in Iran. rdxA gene inactivation,if present in Iranian H pylori strains, may be due to other genetic defects rather than gene deletion.

  3. "Rescue" regimens after Helicobacter pylori treatment failure

    Institute of Scientific and Technical Information of China (English)

    Javier P Gisbert

    2008-01-01

    Helicobacter pylori (H pylori)infection is the main cause of gastritis,gastroduodenal ulcer disease,and gastric cancer.After more than 20 years of experience in Hpylori treatment,in my opinion,the ideal regimen to treat this infection is still to be found.Currently,apart from having to know first-line eradication regimens well,we must also be prepared to face lyeatment failures.Therefore,in designing a treatment strategy we should not focus on the results of primary therapy alone,but also on the final (overall) eradication rate.The choice of a "rescue" treatment depends on which treatment is used initially.If a clarithromycinbased regimen was used initially,a subsequent metronidazole-based treatment (quadruple therapy)may be used afterwards,and then a levofloxacinbased combination would be a third "rescue" option.Alternatively,it has recently been suggested that levofloxacin-based rescue therapy constitutes an encouraging second-line strategy,representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure,with the advantage of efficacy,simplicity and safety.In this case,a quadruple regimen may be reserved as a third-line rescue option.Finally,rifabutin-based rescue therapy constitutes an encouraging empirical fourthline strategy after multiple previous eradication failures with key antibiotics such as amoxicillin,clarithromycin,metronidazole,tetracycline,and levofloxacin.Even after two consecutive failures,several studies have demonstrated that H pylor/eradication can finally be achieved in almost all patients if several rescue therapies are consecutively given.Therefore,the attitude in H pylori eradication therapy failure,even after two or more unsuccessful attempts,should be to fight and not to surrender.

  4. Transcriptional profiling of gastric epithelial cells infected with wild type or arginase-deficient Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Kim Songhee H

    2012-08-01

    Full Text Available Abstract Background Helicobacter pylori causes acute and chronic gastric inflammation induced by proinflammatory cytokines and chemokines secreted by cells of the gastric mucosa, including gastric epithelial cells. Previous studies have demonstrated that the bacterial arginase, RocF, is involved in inhibiting T cell proliferation and CD3ζ expression, suggesting that arginase could be involved in a more general dampening of the immune response, perhaps by down-regulation of certain pro-inflammatory mediators. Results Global transcriptome analysis was performed on AGS gastric epithelial cells infected for 16 hours with a wild type Helicobacter pylori strain 26695, an arginase mutant (rocF- or a rocF+ complemented strain. H. pylori infection triggered altered host gene expression in genes involved in cell movement, death/growth/proliferation, and cellular function and maintenance. While the wild type strain stimulates host inflammatory pathways, the rocF- mutant induced significantly more expression of IL-8. The results of the microarray were verified using real-time PCR, and the differential levels of protein expression were confirmed by ELISA and Bioplex analysis. MIP-1B was also significantly secreted by AGS cells after H. pylori rocF- mutant infection, as determined by Bioplex. Even though not explored in this manuscript, the impact that the results presented here may have on the development of gastritis, warrant further research to understand the underlying mechanisms of the relationship between H. pylori RocF and IL-8 induction. Conclusions We conclude that H. pylori arginase modulates multiple host signaling and metabolic pathways of infected gastric epithelial cells. Arginase may play a critical role in anti-inflammatory host responses that could contribute to the ability of H. pylori to establish chronic infections.

  5. Omeprazole and misoprostol for preventing gastric mucosa effects caused by indomethacin and celecoxib in rats Omeprazol e misoprostol na prevenção de lesões de mucosa gástrica causadas por indometacina e celecoxib em ratos

    OpenAIRE

    Míriam Elias Cavallini; Nelson Adami Andreollo; Konradin Metze; Marina Raquel Araújo

    2006-01-01

    PURPOSE: To evaluate and to compare macro and microscopically the intense injuries of the gastric mucosa of rats which were caused by NSAIDS celecoxib and indomethacin and the gastric cytoprotection with omeprazole and misoprostol. METHODS: The sample is formed by one hundred and fifty Wistar rats with average weight 200 g, distributed in four groups, such as: Group A, subdivided in groups A1 and A2 - pre-treatment with omeprazole (20 mg/rat) during seven days and on the 8th day - use of NSAI...

  6. Co-infection of the Siberian hamster (Phodopus sungorus) with a novel Helicobacter sp. and Campylobacter sp.

    Science.gov (United States)

    Nagamine, Claude M; Shen, Zeli; Luong, Richard H; McKeon, Gabriel P; Ruby, Norman F; Fox, James G

    2015-05-01

    We report the isolation of a novel helicobacter isolated from the caecum of the Siberian hamster (Phodopus sungorus). Sequence analysis showed 97% sequence similarity to Helicobacter ganmani. In addition, we report the co-infection of these Siberian hamsters with a Campylobacter sp. and a second Helicobacter sp. with 99% sequence similarity to Helicobacter sp. flexispira taxon 8 (Helicobacter bilis), a species isolated previously from patients with bacteraemia. Gross necropsy and histopathology did not reveal any overt pathological lesions of the liver and gastrointestinal tract that could be attributed to the Helicobacter or Campylobacter spp. infections. This is the first helicobacter to be identified in the Siberian hamster and the first report of co-infection of Helicobacter spp. and Campylobacter sp. in asymptomatic Siberian hamsters.

  7. Long-term retention on treatment with lumiracoxib 100 mg once or twice daily compared with celecoxib 200 mg once daily: A randomised controlled trial in patients with osteoarthritis

    Directory of Open Access Journals (Sweden)

    Notter Marianne

    2008-03-01

    Full Text Available Abstract Background The efficacy, safety and tolerability of lumiracoxib, a novel selective cyclooxygenase-2 (COX-2 inhibitor, has been demonstrated in previous studies of patients with osteoarthritis (OA. As it is important to establish the long-term safety and efficacy of treatments for a chronic disease such as OA, the present study compared the effects of lumiracoxib at doses of 100 mg once daily (o.d. and 100 mg twice daily (b.i.d. with those of celecoxib 200 mg o.d. on retention on treatment over 1 year. Methods In this 52-week, multicentre, randomised, double-blind, parallel-group study, male and female patients (aged at least 40 years with symptomatic primary OA of the hip, knee, hand or spine were randomised (1:2:1 to lumiracoxib 100 mg o.d. (n = 755, lumiracoxib 100 mg b.i.d. (n = 1,519 or celecoxib 200 mg o.d. (n = 758. The primary objective of the study was to demonstrate non-inferiority of lumiracoxib at either dose compared with celecoxib 200 mg o.d. with respect to the 1-year retention on treatment rate. Secondary outcome variables included OA pain in the target joint, patient's and physician's global assessments of disease activity, Short Arthritis assessment Scale (SAS total score, rescue medication use, and safety and tolerability. Results Retention rates at 1 year were similar for the lumiracoxib 100 mg o.d., lumiracoxib 100 mg b.i.d. and celecoxib 200 mg o.d. groups (46.9% vs 47.5% vs 45.3%, respectively. It was demonstrated that retention on treatment with lumiracoxib at either dose was non-inferior to celecoxib 200 mg o.d. Similarly, Kaplan-Meier curves for the probability of premature discontinuation from the study for any reason were similar across the treatment groups. All three treatments generally yielded comparable results for the secondary efficacy variables and all treatments were well tolerated. Conclusion Long-term treatment with lumiracoxib 100 mg o.d., the recommended dose for OA, was as effective and well

  8. Expression of Helicobacter pylori hspA Gene in Lactococcus lactis NICE System and Experimental Study on Its Immunoreactivity

    Directory of Open Access Journals (Sweden)

    Xiao-Juan Zhang

    2015-01-01

    Full Text Available Aim. The aim of this study was to develop an oral Lactococcus lactis (L. lactis vaccine against Helicobacter pylori (H. pylori. Methods. After L. lactis NZ3900/pNZ8110-hspA was constructed, growth curves were plotted to study whether the growth of recombinant L. lactis was affected after hspA was cloned into L. lactis and whether the growth of empty bacteria, empty plasmid bacteria, and recombinant L. lactis was affected by different concentrations of Nisin; SDS-PAGE and Western blot were adopted, respectively, to detect the HspA expressed by recombinant L. lactis and its immunoreactivity. Results. There was no effect observed from the growth curve after exogenous gene hspA was cloned into L. lactis NZ3900; different concentrations of Nisin did not affect the growth of NZ3900 and NZ3900/pNZ8110, while different concentrations of Nisin inhibited the growth of NZ3900/pNZ8110-hspA except 10 ng/mL Nisin. No HspA strip was observed from SDS-PAGE. Western blot analysis showed that HspA expressed by recombinant bacteria had favorable immunoreactivity. Conclusion. The growth of recombinant L. lactis was suppressed even though a small amount of HspA had been induced to express. Therefore recombinant L. lactis only express HspA which was not suitable to be oral vaccine against Helicobacter pylori.

  9. HELICOBACTER PYLORI PREVALENCE IN PATIENTS WITH CELIAC DISEASE: results from a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Juan LASA

    2015-06-01

    Full Text Available Background Some previously published studies have suggested an inverse relationship between celiac disease and Helicobacter pylori, raising the possibility of the protective role Helicobacter pylori could have against celiac disease development. Nevertheless, this association is inconclusive. Objectives To determine the prevalence of Helicobacter pylori infection in celiac subjects. Methods Between January 2013 and June 2014, patients over 18 years old undergoing upper endoscopy who required both gastric and duodenal biopsies were included for analysis. Enrolled subjects were divided in two groups: those with a diagnosis of celiac disease and those without a celiac disease diagnosis. Helicobacter pylori infection prevalence was compared between groups. Among celiac patients, endoscopic markers of villous atrophy as well as histological damage severity were compared between those with and without Helicobacter pylori infection. Results Overall, 312 patients were enrolled. Seventy two of them had a diagnosis of celiac disease. Helicobacter pylori infection prevalence among celiac disease patients was 12.5%, compared to 30% in non-celiac patients [OR=0.33 (0.15-0.71]. There was not a significant difference in terms of the severity of villous atrophy in patients with Helicobacter pylori infection compared to those without it. There was a slight increase in the prevalence of endoscopic markers in those Helicobacter pylori-negative celiac subjects. Conclusion Helicobacter pylori infection seems to be less frequent in celiac patients; among those celiac subjects with concomitant Helicobacter pylori infection, histological damage degree and presence of endoscopic markers suggesting villous atrophy seem to be similar to those without Helicobacter pylori infection.

  10. Epidemiology of Helicobacter pylori and gastric cancer.

    Science.gov (United States)

    Kikuchi, Shogo

    2002-01-01

    Findings in epidemiological studies of the relationship between Helicobacter pylori and gastric cancer have been inconsistent: many studies have yielded a positive relationship, whereas several studies have shown no relationship. The inconsistency arises because of the occurrence of seroreversion during the period between the time that H. pylori exerts a carcinogenic effect and the time of blood sampling. When this seroreversion is taken into account, there is an epidemiologically positive association between H. pylori status and the risk for gastric cancer. In addition to the epidemiological evidence, experimental studies using Mongolian gerbils have shown that H. pylori infection elevates the risk for gastric cancer. It is concluded that H. pylori is a causal factor for gastric cancer. In the creation of preventive strategies against gastric cancer by the eradication of H. pylori, determination of the time at which H. pylori plays a role as a carcinogen is important. Three hypotheses have been proposed in regard to this timing: that H. pylori infection in childhood or the teenage years acts as a factor that produces precancerous lesions with irreversible damage in the gastric mucosa, that in adulthood it acts as an initiator, and also in adulthood, that it acts as a promoter. As these hypotheses are not mutually exclusive, the extent to which each hypothesis plays a part in explaining gastric carcinogenesis should be evaluated. Only a small proportion of subjects infected with H. pylori have gastric cancer during their lifetime. Interleukin-1 polymorphism, a host factor, and CagA, a virulence factor of H. pylori, are suspected to be risk factors for gastric cancer in subjects with H. pylori infection. Dietary factors, especially vitamin C, and patterns of precancerous lesions also seem to influence the relationship between H. pylori and gastric cancer. H. pylori seems to reduce the risk for esophageal and for some gastric cardia adenocarcinomas. This finding, as

  11. Horizontal versus familial transmission of Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Sandra Schwarz

    2008-10-01

    Full Text Available Transmission of Helicobacter pylori is thought to occur mainly during childhood, and predominantly within families. However, due to the difficulty of obtaining H. pylori isolates from large population samples and to the extensive genetic diversity between isolates, the transmission and spread of H. pylori remain poorly understood. We studied the genetic relationships of H. pylori isolated from 52 individuals of two large families living in a rural community in South Africa and from 43 individuals of 11 families living in urban settings in the United Kingdom, the United States, Korea, and Colombia. A 3,406 bp multilocus sequence haplotype was determined for a total of 142 H. pylori isolates. Isolates were assigned to biogeographic populations, and recent transmission was measured as the occurrence of non-unique isolates, i.e., isolates whose sequences were identical to those of other isolates. Members of urban families were almost always infected with isolates from the biogeographic population that is common in their location. Non-unique isolates were frequent in urban families, consistent with familial transmission between parents and children or between siblings. In contrast, the diversity of H. pylori in the South African families was much more extensive, and four distinct biogeographic populations circulated in this area. Non-unique isolates were less frequent in South African families, and there was no significant correlation between kinship and similarity of H. pylori sequences. However, individuals who lived in the same household did have an increased probability of carrying the same non-unique isolates of H. pylori, independent of kinship. We conclude that patterns of spread of H. pylori under conditions of high prevalence, such as the rural South African families, differ from those in developed countries. Horizontal transmission occurs frequently between persons who do not belong to a core family, blurring the pattern of familial

  12. Investigations into the antibacterial activities of phytotherapeutics against Helicobacter pylori and Campylobacter jejuni.

    Science.gov (United States)

    Cwikla, C; Schmidt, K; Matthias, A; Bone, K M; Lehmann, R; Tiralongo, E

    2010-05-01

    The prevalence of gastric diseases is increasing with H. pylori, the causative agent of acute and chronic gastritis, being a major predisposing factor for peptic ulcer disease and gastric carcinoma. C. jejuni is the most common cause of enteric infections, particularly among children, resulting in severe diarrhoea. Increasing drug resistance of these bacteria against standard antibiotics, and the more widespread use of herbal medicines, favours investigations into additional anti-Helicobacter and anti-Campylobacter effects of phytotherapeutics that are already used for their beneficial effects on bowel and digestive functions. Twenty-one hydroethanol herbal extracts and four essential oils were screened for antibacterial activity using a modification of a previously described micro-dilution assay and compared with the inhibitory effects of antibiotics. The herbal extracts showing the highest growth inhibition of C. jejuni were Calendula officinalis, Matricaria recutita, Zingiber officinale, Salvia officinalis, Foeniculum vulgare and Silybum marianum. Agrimonia eupatoria, Hydrastis canadensis, Filipendula ulmaria and Salvia officinalis were the most active herbal extracts in inhibiting the growth of H. pylori. This study provides evidence for additional beneficial effects of phytotherapeutics marketed for their gastrointestinal effects and identifies new beneficial antibacterial effects for some herbal medicines not currently recommended for gastrointestinal problems. PMID:19653313

  13. Prominent role of γ-glutamyl-transpeptidase on the growth of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Min Gong; Bow Ho

    2004-01-01

    AIM: γ-glutamyl transpeptidase (GGT) has been reported as a virulence and colonizing factor of Helicobacter pylori (H pylori). This study examined the effect of GGT on the growth of H pylori.METHODS: Standard H pylori strain NCTC 11637 and 4clinical isolates with different levels of GGT activity as measured by an enzymatic assay were used in this study. Growth inhibition and stimulation studies were carried out by culturing H pylori in brain heart infusion broth supplemented with specific GGT inhibitor (L-serine sodium borate complex, SBC)or enhancer (glutathione together with glycyl-glycine),respectively. The growth profiles of H pyloriwere determined based on viable bacterial count at time interval.RESULTS: Growth was more profuse for H pylori isolates with higher GGT activity than those present with lower GGT activity. However, in the presence of SBC, growth of H pylori was retarded in a dose dependent manner (P = 0.034). In contrast, higher growth rate was observed when GGT activity was enhanced in the presence of glutathione and glycyl-glycine.CONCLUSION: Higher GGT activity provides an advantage to the growth of H pylori in vitro. Inhibition of GGT activity by SBC resulted in growth retardation. The study shows that GGT plays an important role on the growth of H pylori.

  14. In vitro screening of selected Iranian medicinal plants against Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Zahra Hosseininejad

    2011-01-01

    Full Text Available Helicobacter pylori infection is virtually always associated with duodenal, peptic and gastric ulcers and promotion of gastrointestinal cancer. Some of medicinal plants traditionally have been used for gastrointestinal problems. In the present work, the inhibitory effect of the essential oils of some medicinal plants was evaluated against clinical isolate of H. pylori. H. pylori was isolated from gastric biopsy of patients with gastric complications. Agar diffusion and agar dilution methods were used for evaluating the anti-H. pylori effect and minimum inhibitory concentration (MIC determination of tested plants. The results were reported as mean±SD and differences considered significant at a P value <0.05. The essential oils of Cinnamomum zeylanicum and Zataria multiflora demonstrated potent anti-H. pylori effect with inhibition zone diameter of 24.8 mm and 23.6 mm, respectively. The MIC of both two essential oils was estimated to be 0.3 μl/ml. The essential oils of Heracleum persicum, Syzygium aromaticum and Citrus aurantium exhibited more than 88% inhibition in concentration of 0.3 μl/ml. The essential oils of C. zeylanicum and Z. multiflora might be good candidate for treatment of gastrointestinal disorders caused by H. pylori and it is needed to do further study about these essential oils.

  15. Diagnosis of Helicobacter pylori infection: A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To evaluate effects of diagnostic tests for Helicobacter pylori (H. pylori) infection. Methods: A meta-analysis was conducted in 22 identified studies through Chinese literature searching which were published after 1995 and evaluated diagnostic tests for Helicobacter pylori (H. pylori) infection. Results: Polymerase chain reaction (PCR) had the best performance with diagnostic odds ratio (DOR) of 6.7 (5.5-7.8), followed by 13C urea breath test and Enzyme-linked immunosorbent assay (ELISA) quantitative serological test, with DOR being 6.4 (5.4-7.4) and 4.5 (3.8-5.2), respectively. Conclusion: Non-invasive tests are the appropriate methods for screening H. pylori infection, whereas invasive tests are the best methods for ascertaining the suspected patients.

  16. The presence of Helicobacter pylori in laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Yilmaz, Ismail; Erkul, E; Berber, U; Kucukodaci, Z; Narli, G; Haholu, A; Demirel, D

    2016-03-01

    A definitive relationship between Helicobacter pylori (HP) and upper respiratory tract disorders has not been established. In this case-control study, we investigated the relationship between HP and laryngeal carcinoma by real-time PCR method in Turkey. 74 subjects were enrolled from patients who were admitted to the Otolaryngology Department. Formalin-fixed-paraffin-embedded tissue samples with laryngeal cancer were used and all samples were evaluated by real-time PCR method. Our study population included 72 males and 2 females with a mean age range of 62.7 years. Helicobacter Pylori was detected in only one case. The positive case was also investigated with histopathologic evaluation and HP immunohistochemistry. However, we could not detect HP in this case with both methods. This study revealed that HP might not contribute to the pathogenesis of laryngeal carcinoma. A definitive relationship between HP and upper respiratory tract disorders has not been established.

  17. The role of gastric mucins in interactions with Helicobacter pylori

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    Iwona Radziejewska

    2012-01-01

    Full Text Available Helicobacter pylori is a Gram-negative bacterium which colonizes the stomach of over 50�0of the world’s population. The pathogen is responsible for many diseases including gastritis, ulcers and also gastric cancers. It is said that adherence of bacteria to epithelial cells plays a key role in infection development. Two gastric mucins, components of mucus, are assumed to have an important role in protection against adhesion and in this way in progression of infection. These are a secretory MUC5AC mucin, produced by mucous epithelial cells, and a membrane-bound MUC1 mucin, expressed by epical surfaces of epithelial cells. Interactions with bacteria occur between carbohydrate antigens of mucins and specific adhesins of the Helicobacter pylori surface. In this paper we present the latest knowledge about these intriguing interactions of both mucins and their interplay with the pathogen providing protection against infection.

  18. Helicobacter pylori colonization in infants and its relation to childhood morbidity

    International Nuclear Information System (INIS)

    Helicobacter pylori infection is universally reported from all over the world including both developed and developing countries. The prevalence of Helicobacter pylori infection in Pakistan is unknown. Although a few studies have been done in adults, there are no studies looking at the prevalence of Helicobacter pylori colonization especially in children. In addition, a number of symptoms such as nonspecific abdominal pain, diarrhea and malnutrition etc. are attributed to it though most cases of Helicobacter pylori colonization remain asymptomatic. The association between Helicobacter pylori and gastrointestinal symptoms however, remains controversial. Hence in order to determine the prevalence of Helicobacter pylori infection, its time of acquisition and to look at its correlation with diarrhea-associated morbidity, we proposed to do the present study. In this study we will look for the evidence of Helicobacter colonization in infants with the non-invasive techniques using 13C urea breath test and stool ELISA for Helicobacter pylori every at three month interval in a cohort of infants from a periurban community in Karachi Pakistan. (author)

  19. Efficacy of the Therapy of Goiter with Subclinical Hypothyroidism Associated with Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    G M Panyushkina

    2008-12-01

    Full Text Available Article presented results of the treatment (150 mcg/day KI of goitre with subclinical hypothyroidism associated with Helicobacter pylori infection in 54 women. In conclusion total eradication of Helicobacter pylori could increase efficacy of goitre treatment up to 90%.

  20. Treatment for Helicobacter pylori infection and risk of Parkinson's disease in Denmark

    DEFF Research Database (Denmark)

    Nielsen, H H; Qiu, J; Friis, S;

    2012-01-01

    It has been speculated that gastrointestinal infection with Helicobacter pylori (HP) contributes to the development of Parkinson's disease (PD). We used nationwide Danish registers to investigate this hypothesis.......It has been speculated that gastrointestinal infection with Helicobacter pylori (HP) contributes to the development of Parkinson's disease (PD). We used nationwide Danish registers to investigate this hypothesis....

  1. "Helicobacter Pylori" Infection in Five Inpatient Units for People with Intellectual Disability and Psychiatric Disorder

    Science.gov (United States)

    Clarke, David; Vemuri, Murali; Gunatilake, Deepthi; Tewari, Sidhartha

    2008-01-01

    Background: A high prevalence of "Helicobacter pylori" infection has been reported among people with intellectual disability, especially those residing in hospital and similar settings. Surveys of inpatients have found unusually high rates of gastrointestinal malignancy, to which "H. pylori" infection predisposes. Methods: "Helicobacter pylori"…

  2. Cloning and Expression of Helicobacter Pylori CagA Gene Antigenic Regions in E. coli

    Directory of Open Access Journals (Sweden)

    Mahdye maleki

    2016-04-01

    Conclusions: The results of this study proved the successful cloning of the epitope area. The recombinant protein can probably be introduced as a good candidate for the production of IgY from the chickenimmunized and the control of Helicobacter pylori infection in humans. It could also be possibly used for the design of diagnostic kits and vaccines for Helicobacter pylori

  3. Helicobacter pylori infection and respiratory diseases: a review

    OpenAIRE

    Roussos, Anastasios; Philippou, Nikiforos; Gourgoulianis, Konstantinos I

    2003-01-01

    In the past few years, a variety of extradigestive disorders, including cardiovascular, skin, rheumatic and liver diseases, have been associated with Helicobacter pylori (H. pylori) infection. The activation of inflammatory mediators by H. pylori seems to be the pathogenetic mechanism underlying the observed associations. The present review summarizes the current literature, including our own studies, concerning the association between H. pylori infection and respiratory diseases.

  4. An exploratory study of Helicobacter suis control strategies

    OpenAIRE

    Vermoote, Miet

    2013-01-01

    Helicobacter suis is a Gram-negative, spiral-shaped bacterium that colonizes the stomach of the majority of slaughter pigs worldwide. An infection with this microorganism has been associated with erosive and ulcerative lesions in the non-glandular part of the porcine stomach and with chronic gastritis. A reduction in daily weight gain in experimentally infected pigs has been described, emphasizing the importance of H. suis infections for the pig industry. Furthermore, it is the most prevalent...

  5. Complex polysaccharides as PCR inhibitors in feces: Helicobacter pylori model.

    OpenAIRE

    Monteiro, L; Bonnemaison, D; Vekris, A. (A.); Petry, K G; Bonnet, J; Vidal, R.; Cabrita, J; Mégraud, F.

    1997-01-01

    A model was developed to study inhibitors present in feces which prevent the use of PCR for the detection of Helicobacter pylori. A DNA fragment amplified with the same primers as H. pylori was used to spike samples before extraction by a modified QIAamp tissue method. Inhibitors, separated on an Ultrogel AcA44 column, were characterized. Inhibitors in feces are complex polysaccharides possibly originating from vegetable material in the diet.

  6. Complex polysaccharides as PCR inhibitors in feces: Helicobacter pylori model.

    Science.gov (United States)

    Monteiro, L; Bonnemaison, D; Vekris, A; Petry, K G; Bonnet, J; Vidal, R; Cabrita, J; Mégraud, F

    1997-04-01

    A model was developed to study inhibitors present in feces which prevent the use of PCR for the detection of Helicobacter pylori. A DNA fragment amplified with the same primers as H. pylori was used to spike samples before extraction by a modified QIAamp tissue method. Inhibitors, separated on an Ultrogel AcA44 column, were characterized. Inhibitors in feces are complex polysaccharides possibly originating from vegetable material in the diet. PMID:9157172

  7. Repair and Antirepair DNA Helicases in Helicobacter pylori▿ †

    OpenAIRE

    Kang, Josephine; Martin J Blaser

    2008-01-01

    Orthologs of RecG and RuvABC are highly conserved among prokaryotes; in Escherichia coli, they participate in independent pathways that branch migrate Holliday junctions during recombinational DNA repair. RecG also has been shown to directly convert stalled replication forks into Holliday junctions. The bacterium Helicobacter pylori, with remarkably high levels of recombination, possesses RecG and RuvABC homologs, but in contrast to E. coli, H. pylori RecG limits recombinational repair. We no...

  8. Survey of general practitioners' knowledge about Helicobacter pylori infection

    OpenAIRE

    Peksen Yildiz; Sunter Ahmet; Canbaz Sevgi; Leblebicioglu Hakan

    2005-01-01

    Abstract Background Helicobacter pylori, occurring throughout the world and causing gastroduodenal diseases, is one of the most common chronic bacterial agents in humans. The purpose of this study was to measure the general practitioners' (GPs) knowledge and practices pertaining to H. pylori infection. Methods A cross-sectional type questionnaire survey was conducted in all of 19 primary health care centres (PHCC) in Samsun, Turkey, between November 1 and December 31, 2003. The questionnaire ...

  9. Helicobacter pylori in the dental plaque of healthy Saudis

    OpenAIRE

    Contractor Qais; Tahir Mohammed; Naseem Shahzad; Ahmad Shamweel

    1998-01-01

    The objective of this study is to determine the presence of Helicobacter pylori in the dental plaque of healthy Saudis and its relation to dental care. One hundred randomly selected healthy Saudis attending the dental clinic were assessed for oral hygiene and periodontal disease by dental examination. Information about the use of toothpaste, chewing stick, smoking and dentures was obtained. Samples of dental plaque were collected after scoring it according to the plaque index. Presence of H. ...

  10. Correlation between Oral Hygiene and Helicobacter Pylori Infection

    OpenAIRE

    Nasrin Esfahanizadeh; Rahele Modanlou

    2010-01-01

    As introduced by different studies, dental plaque is known as a reservoir of Helicobacter Pylori (HP) and a potential source for gastric re-infection. Also, it has been demonstrated that individuals with gastric HP infection manifest a greater plaque index and a higher incidence rate for gingivitis. The goal of the present research was survey of severity and prevalence of periodontal diseases associated with gastric HP infection among patients having referred to the endoscopy wards of Imam Kh...

  11. The effect of Helicobacter pylori on asthma and allergy

    OpenAIRE

    D'Elios, Mario Milco

    2010-01-01

    Amedeo Amedei1, Gaia Codolo2, Gianfranco Del Prete1, Marina de Bernard2, Mario M D’Elios11Policlinico AOU Careggi, Department Internal Medicine, University of Florence, Italy; 2Venetian Institute of Molecular Medicine, University of Padua, ItalyAbstract: Current evidence indicates an inverse association between Helicobacter pylori and asthma and allergy. H. pylori is a Gram-negative bacterium which represents the major cause of peptic ulcer and gastric cancer, and preferentially eli...

  12. Persistence of helicobacter pylori in heterotrophic drinking-water biofilms

    OpenAIRE

    Gião, M. S.; Azevedo, N. F.; Wilks, S. A.; Vieira, M. J.; Keevil, C. W.

    2008-01-01

    Although the route of transmission of Helicobacter pylori remains unknown, drinking water has been considered a possible transmission vector. It has been shown previously that, in water, biofilms are a protective niche for several pathogens, protecting them from stressful conditions, such as low carbon concentration, shear stress, and less-than-optimal temperatures. In this work, the influence of these three parameters on the persistence and cultivability of H. pylori in drinking-water biofil...

  13. Helicobacter pylori associated gastric intestinal metaplasia: Treatment and surveillance

    OpenAIRE

    Liu, Kevin Sze-Hang; Wong, Irene Oi-Ling; Leung, Wai K.

    2016-01-01

    Gastric cancer (GC) is one of the leading causes of cancer related death in the world, particularly in East Asia. According to the Correa’s cancer cascade, non-cardia GC is usually developed through a series of mucosal changes from non-atrophic gastritis to atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia and adenocarcinoma. Atrophic gastritis and IM are therefore generally considered to be pre-neoplastic gastric lesions. Helicobacter pylori (H. pylori) infection is an important...

  14. Association of Helicobacter pylori infection with type 2 diabetes

    OpenAIRE

    Sarita Bajaj; Lokendra Rekwal; SP Misra; Vatsala Misra; Rakesh Kumar Yadav; Anubha Srivastava

    2014-01-01

    Introduction: Helicobacter pylori (H. pylori) infection has been associated with increased levels of inflammatory cytokines and subsequent insulin resistance and epidemiologically linked to type 2 diabetes. Objectives: To study the prevalence rate of H. pylori infection in type 2 diabetes and its relation with HbA1C levels. Materials and Methods: In this cross-sectional case-control study, 80 patients (≥18 years) who met the Americans with Disabilities Act (ADA) criteria for diabetes were rec...

  15. “Rescue” regimens after Helicobacter pylori treatment failure

    OpenAIRE

    Javier P Gisbert

    2008-01-01

    Helicobacter pylori (H pylori) infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After more than 20 years of experience in H pylori treatment, in my opinion, the ideal regimen to treat this infection is still to be found. Currently, apart from having to know first-line eradication regimens well, we must also be prepared to face treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone,...

  16. Adherence of Helicobacter pylori to primary human gastrointestinal cells.

    OpenAIRE

    Clyne, M.; Drumm, B

    1993-01-01

    Helicobacter pylori adheres only to gastric cells in vivo. However, the organism adheres to a wide variety of nongastric cells in vitro. In this study, we have used flow cytometry to assess the adherence of H. pylori to primary epithelial cells isolated from gastric, duodenal, and colonic biopsy specimens by collagenase digestion. After incubation of bacteria and cells together and subsequent staining with a two-stage fluorescein isothiocyanate-labelled H. pylori antibody method, cells with a...

  17. Eradicating Helicobacter pylori reduces hypergastrinaemia during long term omeprazole treatment

    OpenAIRE

    El-Nujumi, A; Williams, C; Ardill, J; Oien, K; McColl, K

    1998-01-01

    Background—Both proton pump inhibitor drug treatment and Helicobacter pylori infection cause hypergastrinaemia in man. 
Aims—To determine whether eradicating H pylori is a means of reducing hypergastrinaemia during subsequent proton pump inhibitor treatment. 
Methods—Patients with H pylori were randomised to treatment with either anti-H pylori or symptomatic treatment. One month later, all received four weeks treatment with omeprazole 40 mg/day for one month followed by 2...

  18. Metachronous gastric cancer after successful Helicobacter pylori eradication

    OpenAIRE

    Shiotani, Akiko; Haruma, Ken; David Y Graham

    2014-01-01

    The high incidence of gastric cancer in Japan initially resulted in establishment of a country-wide gastric cancer screening program to detect early and treatable cancers. In 2013 countrywide Helicobacter pylori (H. pylori) eradication was approved coupled with endoscopy to assess for the presence of chronic gastritis. Current data support the notion that cure of the infection in those with non-atrophic gastritis will prevent development of gastric cancer. However, while progression to more s...

  19. Canadian Helicobacter pylori Consensus Conference Update: Infections in Adults

    OpenAIRE

    Hunt, RH; Fallone, CA; Thomson, ABR

    1999-01-01

    The first Canadian Helicobacter pylori Consensus Conference took place in April 1997. The initial recommendations of the conference were published in early 1998. An update meeting was held in June 1998, and the present paper updates and complements the earlier recommendations. Key changes included the following: the recommendation for testing and treating H pylori infection in patients with known peptic ulcer disease was extended to testing and treating patients with ulcer-like dyspepsia; it ...

  20. Structure, function and localization of Helicobacter pylori urease.

    OpenAIRE

    Dunn, B E; Phadnis, S H

    1998-01-01

    Helicobacter pylori is the causative agent of most cases of gastritis. Once acquired, H. pylori establishes chronic persistent infection; it is this long-term infection that, is a subset of patients, leads to gastric or duodenal ulcer, gastric cancer or gastric MALT lymphoma. All fresh isolates of H. pylori express significant urease activity, which is essential to survival and pathogenesis of the bacterium. A significant fraction of urease is associated with the surface of H. pylori both in ...

  1. Detection of oral Helicobacter Pylori infection using saliva test cassette

    OpenAIRE

    Yu, Min; Zhang, Xue-Yan; Yu, Qing

    2015-01-01

    Objective: To investigate the incidence of oral infection with Helicobacter pylori (H. pylori) and identify related epidemiological factors among freshmen of four colleges in Yancheng. Methods: The data, scored positive or negative, were collected on 160 individuals who had been diagnosed by H. pylori Saliva Test Cassette (HPS) during October 2013 to October 2014. H. pylori Saliva Test Cassette (HPS) is to use colloidal gold technique to specifically identify urease in saliva. A standard ques...

  2. Diagnosis of Helicobacter pylori: What should be the gold standard?

    OpenAIRE

    Patel, Saurabh Kumar; Pratap, Chandra Bhan; Jain, Ashok Kumar; Gulati, Anil Kumar; Nath, Gopal

    2014-01-01

    Since the discovery of Helicobacter pylori (H. pylori) in 1983, numerous detection methods for the presence of the bacterium have been developed. Each one of them has been associated with advantages and disadvantages. Noninvasive tests such as serology, 13C urea breath test (UBT) and stool antigen tests are usually preferred by the clinicians. Serology has its own limitation especially in endemic areas while 13C UBT is technically very demanding. The stool antigen detection method, although s...

  3. Is saliva serology useful for the diagnosis of Helicobacter pylori?

    OpenAIRE

    Christie, J.M.; McNulty, C A; Shepherd, N A; Valori, R M

    1996-01-01

    BACKGROUND: The Cortecs Diagnostics Helisal Assay test is a quantitative immunoassay for salivary IgG antibodies against Helicobacter pylori. Saliva can be obtained simply with the kit in the general practitioners surgery. AIMS: To compare the new saliva serological test for H pylori with 'gold standard' evidence of H pylori infection (antral biopsy specimens for histology, culture, and urease test) and a new serum serological test. PATIENTS: Eighty six unselected dyspeptic patients undergoin...

  4. Interaction of Helicobacter pylori with glycosylated salivary proteins

    OpenAIRE

    Walz, Anke

    2006-01-01

    Since the discovery of Helicobacter pylori (H. pylori) in 1983 enormous progress has been made in determining the pathogenesis of this microbe in gastric disease. While the way of transmission is still under dispute, it is generally accepted that H. pylori must reach the stomach via the oral cavity. During this passage it comes into contact with salivary components. However, there are only few studies about interactions of H. pylori with salivary components and no study about the influence of...

  5. Evaluation of Salivary Antibodies to Detect Infection with Helicobacter pylori

    OpenAIRE

    1997-01-01

    Helicobacter pylori infection is an important cause of peptic ulcer disease and chronic gastritis. Infection with this bacterium stimulates the production of immunoglobulin (Ig) G antibody. Salivary IgG antibody tests to detect H pylori infection offer a convenient and noninvasive method of diagnosis. To evaluate an IgG salivary antibody kit, saliva was collected from 157 out-patients with dyspepsia referred for endoscopy to a tertiary centre. A salivary IgG ELISA antibody assay was performed...

  6. Noninvasive Diagnostic Tests for Helicobacter Pylori Infection in Children

    OpenAIRE

    Koletzko, Sibylle

    2005-01-01

    Noninvasive tests can be used for the initial diagnosis of Helicobacter pylori infection and to monitor the success of eradication therapy. In populations with a low prevalence of H pylori infection (children living in North America and Europe), a high sensitivity is required to make the test valuable for clinical practice. The 13C-urea breath test has been validated in children of different age groups in a significant number of infected and noninfected children in several countries and, thus...

  7. On the routes of Helicobacter pylori transmission among the humans

    OpenAIRE

    Guimarães, N.

    2011-01-01

    Helicobacter pylori is a spiral, microaerophilic, Gram-negative bacterium that colonizes the human stomach and has been associated with the pathogenesis of chronic gastritis, peptic ulcer disease and gastric carcinoma. Since the isolation of H. pylori, numerous studies have been published addressing the prevalence and epidemiology of the infection, the relationship with disease, the identification and characterization of virulence factors and their role in pathogenesis. Neverth...

  8. PCR Detection of Helicobacter pylori in Clinical Samples

    OpenAIRE

    Rimbara, Emiko; Sasatsu, Masanori; David Y Graham

    2013-01-01

    Helicobacter pylori is an important pathogen whose primary niche is the human stomach. H. pylori is etio-logically associated with gastric inflammation (gastritis), peptic ulcer disease, and gastric cancer. Both noninvasive (e.g., urea breath and stool antigen tests) and invasive (gastric biopsy for histology, culture, or PCR) tests are used for diagnosis. PCR detection of H. pylori has been reported using a variety of clinical samples including gastric biopsy, gastric juice, saliva, dental p...

  9. Validation of a New Saliva Test for Helicobacter pylori Infection

    OpenAIRE

    Bathe, OF; Rae, AJ; Zetler, P; Cleator, IGM

    1996-01-01

    The purpose of this study was to evaluate a recently introduced saliva test measuring immunoglobulin (Ig) G antibodies to Helicobacter pylori by enzyme-linked immunosorbent assay (ELISA). ELISA has previously been validated against IgG serological tests; however, it is not considered the definitive test for H pylori infection. Using endoscopic antral biopsies as the ’gold standard’ for comparison, the saliva test was validated on 70 patients with upper gastrointestinal symptoms admitted to St...

  10. Intrafamillial Clustering of Helicobacter pylori Infection in Saubi Arabia

    OpenAIRE

    Al-Knawy, BA; Ahmed, M-Elbagir K; Mirdad, S; ElMekki, A; Al-Ammari, O

    2000-01-01

    AIM: To study the pattern of Helicobacter pylori infection among family members in the Saudi population.METHODS: A cross-sectional, population-based, seroepidemiological study of family members was undertaken in a Saudi population using saliva H pylori immunoglobulin (Ig) G antibodies (Helisal kit).RESULTS: A total of 42 families comprising 271 children and 84 parents were studied (355 subjects; mean age 23 years, SD 19 years) The overall frequencies of H pylori IgG antibodies in mothers, fat...

  11. Helicobacter pylori and oral pathology: Relationship with the gastric infection

    OpenAIRE

    Adler, Isabel; Muiño, Andrea; Aguas, Silvia; Harada, Laura; Diaz, Mariana; Lence, Adriana; Labbrozzi, Mario; Muiño, Juan Manuel; Elsner, Boris; Avagnina, Alejandra; Denninghoff, Valeria

    2014-01-01

    Helicobacter pylori (H. pylori) has been found in the oral cavity and stomach, and its infection is one of the most frequent worldwide. We reviewed the literature and conducted a Topic Highlight, which identified studies reporting an association between H. pylori-infection in the oral cavity and H. pylori-positive stomach bacterium. This work was designed to determine whether H. pylori is the etiologic agent in periodontal disease, recurrent aphthous stomatitis (RAS), squamous cell carcinoma,...

  12. Helicobacter pylori-coccoid forms and biofilm formation

    DEFF Research Database (Denmark)

    Andersen, Leif Percival; Rasmussen, Lone

    2009-01-01

    be detected by PCR in water supplies. There is no substantial evidence for viable H. pylori persisting in water supplies. Epidemiological studies suggest that environmental water is a risk factor for H. pylori infection when compared with tap water, and formation of H. pylori biofilm cannot be excluded....... Helicobacter pylori does not seem to take part in biofilm formation in the oral cavity even though the bacterium may be detected....

  13. The gastric microbial community, Helicobacter pylori colonization, and disease

    OpenAIRE

    Martin, Miriam E.; Solnick, Jay V.

    2014-01-01

    Long thought to be a sterile habitat, the stomach contains a diverse and unique community of bacteria. One particular inhabitant, Helicobacter pylori, colonizes half of the world’s human population and establishes a decades-long infection that can be asymptomatic, pathogenic, or even beneficial for the host. Many host and bacterial factors are known to influence an individual’s risk of gastric disease, but another potentially important determinant has recently come to light: the host microbio...

  14. Endoscopic gastritis, serum pepsinogen assay, and Helicobacter pylori infection

    OpenAIRE

    Lee, Sun-Young

    2016-01-01

    Endoscopic findings of the background gastric mucosa are important in the Helicobacter pylori-seroprevalent population. It is strongly correlated not only with the risk of gastric cancer, but also with the excretion ability of gastric mucosa cells. In noninfected subjects, common endoscopic findings are regular arrangement of collecting venules, chronic superficial gastritis, and erosive gastritis. In cases of active H. pylori infection, nodularity on the antrum, hemorrhagic spots on the fund...

  15. Prevalence of peptic ulcer in Helicobacter pylori positive blood donors.

    OpenAIRE

    Vaira, D; Miglioli, M; Mulè, P; Holton, J; M. Menegatti; Vergura, M; Biasco, G.; Conte, R.; Logan, R P; Barbara, L

    1994-01-01

    This study aimed to determine the importance of raised antibodies to Helicobacter pylori in an asymptomatic population. A total of 128 asymptomatic blood donors who were seropositive for H pylori and consented to endoscopy were investigated. These subjects were from a population of 1010 blood donors screened for antibodies to H pylori. A questionnaire was completed to determine if any subjects had complained of symptoms, and they subsequently had endoscopy. Altogether 121 of 128 were positive...

  16. Kyoto global consensus report on Helicobacter pylori gastritis

    OpenAIRE

    Sugano, Kentaro; Tack, Jan; Kuipers, Ernst J.; David Y Graham; El-Omar, Emad M.; Miura, Soichiro; Haruma, Ken; Asaka, Masahiro; Uemura, Naomi; Malfertheiner, Peter

    2015-01-01

    Objective To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis. Design Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels ...

  17. Eradication of Helicobacter pylori: therapies and clinical implications.

    OpenAIRE

    O'Connor, H J

    1992-01-01

    This review presents a critical evaluation of the role of Helicobacter pylori eradication in the management of peptic ulcer disease and non-ulcer dyspepsia. On current evidence, H. pylori eradication therapy seems likely to emerge as the most rational and cost-effective treatment for duodenal ulcer. The role of H. pylori eradication in the treatment of gastric ulcer and non-ulcer dyspepsia is unclear and requires further study. The emerging problem of antibiotic resistance in H. pylori is of ...

  18. The immunohistochemical demonstration of Helicobacter pylori in rectal ectopia.

    LENUS (Irish Health Repository)

    Corrigan, Mark Anthony

    2009-08-01

    The finding of heterotopic gastric mucosa in the rectum is rare, with less than 40 reported cases in the literature. A condition of unknown etiology, several hypotheses exist including infectious and congenital. We report a case of ectopic gastric tissue in the rectum of a 47-year-old female, and her subsequent clinical course. Furthermore for the first time, we present immunohistologic evidence of the presence of Helicobacter pylori in rectal ectopic gastric tissue.

  19. Seropositivity to Helicobacter pylori and risk of pancreatic cancer

    OpenAIRE

    Yu, Guoqin; Murphy, Gwen; Michel, Angelika; Weinstein, Stephanie J.; Männistö, Satu; Albanes, Demetrius; Pawlita, Michael; Stolzenberg-Solomon, Rachael Z

    2013-01-01

    Helicobacter pylori seropositivity has been inconsistently associated with pancreatic cancer. We, therefore, investigated the association between H. pylori seropositivity and pancreatic cancer in a case-control study nested within Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) cohort of male Finnish male smokers. Pancreatic cancer cases (n=353) and control subjects (n=353) were matched on date of baseline serum collection, age at randomization, and follow-up time (up to 23.9 y...

  20. Tolerance ability of Lactobacillus from human gastric mucosa and its antagonistic activity against Helicobacter pylori%人胃源乳杆菌耐受性及抗幽门螺杆菌活性的鉴定

    Institute of Scientific and Technical Information of China (English)

    黄微微; 郭刚; 宋阳; 曾本华; 张卫军; 解庆华; 杨致邦

    2013-01-01

    This study aims to screen Lactobacillus strains with Helicobacter pylori antagonistic activity from human gastric mucosa and offer the best research object for the study of the interaction between Lactobacillus and Helicobacter pylori. Six Lactobacillus strains were isolated from the gastric mucosa of 21 people who did gastroscope inspection . The resistant ability of Lactobacillus with different pH (2 .5-4 .5) and bile salt (0 .05% -0 .2% ) were detected . The research also combined with the determination of their antagonistic potential against Helicobacter pylori by oxford plate assay system and the ability inhibited Helicobacter pylori adhere to gastric epithelial cells . Lactobacillus strain L3 had the largest acid production in six strains and could tolerant high acid and high bile salts . The biggest inhibition zones formed when live bacteria and supernatant of strain L3 reacted on Helicobacter pylori, and certain inhibition ability to Escherichia coli and Stap hylococcus aureus were found, which were significantly different between any two of the same treatment liquid groups (P<0 .05). It also made the maximum decrease in Helicobacter pylori adhered to gastric epithelial cells . Lactobacillus strain L3 isolated from human gastric mucosa had strong antagonistic activity on Helicobacter pylori, This study provides basis for the microcological therapy of Helicobact-er pylori related diseases .%目的 分离自人胃粘膜的乳杆菌抗幽门螺杆菌活性的筛选,为观察乳杆菌与幽门螺杆菌相互作用寻找合适的研究对象.方法 从21例胃镜检查者的胃粘膜组织中分离鉴定出6株乳杆菌,检测其在pH 2.5~pH 4.5和含0.05%~0.2%胆盐条件下的耐受性,并结合琼脂扩散牛津杯法检测其抑制幽门螺杆菌生长的能力及通过细胞试验检测其抗幽门螺杆菌粘附人胃上皮细胞的活性.结果 6株乳杆菌分离株中L3产酸量最大,耐酸和高浓度胆盐,其活菌和上清液在血平板中对

  1. [ABO BLOOD GROUPS AS RISK FACTOR IN HELICOBACTER PYLORI INFECTION

    Science.gov (United States)

    Gonzáles Flores, Pedro Alejandro; Díaz Ferrer, Javier Omar; Monge Salgado, Eduardo; Watanabe Varas T, Teresa

    2000-01-01

    TITLE: ABO blood groups as risk factor in Helicobacter pylori infection.OBJECTIVE: To asses the relation between ABO blood groups and Helicobacter pylori (Hp) infection. METHODS: The present is a case and control study. A study population of dyspeptic patients who underwent upper gastrointestinal endoscopy was selected. Four biopsies were taken from the antrum and the body of the stomach and blood group was typified. Patients with gastrectomy, gastric cancer, treated for Hp infection in the previous six months or without blood group typification were excluded. The population sample was found using EPIINFO 5.1 program. We called case to every patient with Hp (+) biopsy and control all with Hp (-) biopsy. The risk of the infection was calculated with the OR (Odds ratio) and the study sample was compared with the blood bank control group using the Chi-square test (pblood groups between the study population and the blood bank control. When we compared the ABO blood distribution between patients Hp (+) and Hp (-) we found significant differences for blood group O (p=0.004) and blood group A (p=0.03). Statistical analysis revealed an OR=2,22 for the blood group O and OR=0,5 for the blood group A.CONCLUSIONS: 1) The ABO blood group distribution is different in patients with Hp infection compared with those without Hp infection. 2) Blood group O would be a moderate risk factor for infection by Helicobacter pylori. PMID:12140571

  2. Helicobacter pylori infection in apparently healthy South Indian children

    International Nuclear Information System (INIS)

    Helicobacter pylori infection has been established as a major cause of chronic gastritis in adults, and it has been implicated in the genesis of gastric carcinomas and the development of gastric and duodenal ulcers. It is now postulated that neatly 90% of the adult population in developing countries may be affected with the infection since childhood. Earlier studies on Indians using serology and endoscopic biopsy have shown a high incidence of H. pylori infection in small numbers of patients. The 13C-urea breath test, which is simple, specific and non-invasive, is also increasingly being used to determine the presence of Helicobacter pylori infection. Preliminary data from India has shown a high prevalence in the urban Indian environment, and there is an urgent need to quantify the prevalence of H. pylori infections on an epidemiological basis in both urban and rural settings. It is also important to study the possible impact of this infection on growth in children, particularly in environments with low sanitation and high crowding. In this paper, we outline a proposal to study the prevalence of Helicobacter pylori infections in children from the following different environments: urban middle socio-economic class, urban slum, rural middle socio-economic class and rural village. (author)

  3. Isolation and identification of Helicobacter spp, from canine and feline gastric mucosa

    DEFF Research Database (Denmark)

    Jalava, K.; On, Stephen L.W.; VanDamme, P.A.R.;

    1998-01-01

    It is known that virtually all healthy adult dogs and cats harbor spiral helicobacters in their gastric mucosa, Three species, Helicobacter felis, Helicobacter bizzozeronii, and Helicobacter salomonis have been isolated in vitro from the gastric mucosa of these animals. The aims of this study were...... conventional phenotypic tests, whole-cell protein profiling, and ultrastructural analysis in identifying the different species isolated from canine and feline gastric mucose. We cultured 95 and 22 gastric mucosal biopsies from dogs and cats, respectively. Twenty-one H. bizzozeronii strains, 8 H. felis strains......, 8 H. salomonis strains, 3 mixed cultures, 2 "Flexispira rappini"-like organisms, and 3 as get uncharacterized strains were isolated from the dogs, and 3 H. felis strains were isolated from the cats. The methods used here yielded Helicobacter isolation rates of 51% from dogs and 13.6% from cats...

  4. Implications of Antibiotic Resistance in the Management of Helicobacter pylori Infection: Canadian Helicobacter Study Group

    Directory of Open Access Journals (Sweden)

    RH Hunt

    2000-01-01

    Full Text Available Eradication of Helicobacter pylori from the gastric and duodenal mucosa is an important clinical goal in the treatment of infected patients with peptic ulcer disease and other H pylori-associated conditions. Although several oral drug combination regimens are associated with eradication rates of approximately 85% in controlled trials, the success rate in patients infected with a resistant strain of H pylori is closer to 75%. Resistance to metronidazole and clarithromycin, which are common components of combination treatment regimens, is of greatest concern. Reported rates of H pylori resistance to various antibiotics vary considerably. In Canada, the data documenting H pylori susceptibility are limited but suggest that resistance to these antibiotics varies geographically and within specific treatment groups. Although susceptibility testing is not a prerequisite for initial treatment of individual patients infected with H pylori, formal efforts to identify and monitor both the causes and prevalence of antibiotic resistance across Canada are a much needed step in the ongoing management of this important infection. Recommended treatment regimens may be useful, even for treating apparently resistant H pylori strains. However, it is important to understand the mechanisms of the development of resistant strains to manage patients with treatment failure better.

  5. Helicobacter pylori and gastric or duodenal ulcer.

    Science.gov (United States)

    2016-01-01

    In patients with gastric or duodenal ulcer associated with Helicobacter pylori, treatment of the infection improves healing and prevents complications and recurrences. The drug regimen generally consists of a high-dose proton-pump inhibitor (PPI) such as omeprazole plus antibiotics. Using the standard Prescrire methodology, we conducted a review of the literature in order to determine the standard empirical antibiotic regimen for H. pylori infection in adults with gastric or duodenal ulcer in France. In 2015, due to an increase in H. pylori resistance to clarithromycin, a 7-day course of the PPI + clarithromycin + amoxicillin combination is effective in only about 70% of cases. A Cochrane systematic review and meta-analysis of trials involving thousands of patients suggests that prolonging treatment with a PPI + amoxicillin + clarithromycin or a PPI + amoxicillin + metronidazole to 10 or 14 days improves the rate of H. pylori eradication by 5% to 10%. A metanalysis of seven trials including a total of about 1000 patients showed that combination therapy with a PPI + amoxicillin + clarithromycin + metronidazole for 5 days eradicates H. pylori in about 90% of cases, compared to about 80% of cases with a PPI + amoxicillin + clarithromycin given for 7 days. Sequential treatment with amoxicillin for 5 days, followed by clarithromycin + metronidazole for 5 days, has also been tested in thousands of patients. Efficacy and adverse effects were similar to those observed when the same antibiotics were taken simultaneously for 5 days. In randomised trials, replacing clarithromycin or amoxicillin with a fluoroquinolone yielded conflicting results. In 2009, nearly 20% of H. pylori isolates were resistant to levofloxacin in France. Tetracycline has only been evaluated in combination with bismuth. The few available data on doxycycline suggest that its efficacy is similar to that of tetracycline. A fixed-dose combination of bismuth subcitrate potassium + metronidazole

  6. Prevalence of Helicobacter pylori infection and related gastroduodenal lesions in spouses of Helicobacter pylori positive patients with duodenal ulcer.

    OpenAIRE

    Parente, F.; Maconi, G; Sangaletti, O; Minguzzi, M; Vago, L; Rossi, E.; Bianchi Porro, G

    1996-01-01

    BACKGROUND: To date, very few studies have evaluated the risk of infection among spouses of Helicobacter pylori positive patients and their results are conflicting. AIM: To assess the seroprevalence of H pylori infection in spouse of H pylori positive patients with duodenal ulcer as compared with age and sex matched volunteer blood donors, as well as the frequency of endoscopic gastroduodenal lesions in these spouses, according to the presence or absence of gastrointestinal complaints. METHOD...

  7. A comparative study of clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori infection in gallbladder mucosa.

    Directory of Open Access Journals (Sweden)

    Di Zhou

    Full Text Available BACKGROUND: Helicobacter pylori has been isolated from 10%-20% of human chronic cholecystitis specimens but the characteristics of "Helicobacter pylori positive cholecystitis" remains unclear. This study aims to compare the clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori infection in gallbladder mucosa. METHODS: Three hundred and twenty-six chronic cholecystitis patients were divided into two groups according to whether Helicobacter pylori could be detected by culture, staining or PCR for Helicobacter 16s rRNA gene in gallbladder mucosa. Positive samples were sequenced for Helicobacter pylori-specific identification. Clinical parameters as well as pathological characteristics including some premalignant lesions and the expression levels of iNOS and ROS in gallbladder were compared between the two groups. RESULTS: Helicobacter pylori infection in gallbladder mucosa was detected in 20.55% of cholecystitis patients. These patients had a higher prevalence of acid regurgitation symptoms (p = 0.001, more histories of chronic gastritis (p = 0.005, gastric ulcer (p = 0.042, duodenal ulcer (p = 0.026 and higher presence of Helicobacter pylori in the stomach as compared to patients without Helicobacter pylori infection in the gallbladder mucosa. Helicobacter pylori 16s rRNA in gallbladder and gastric-duodenal mucosa from the same individual patient had identical sequences. Also, higher incidences of adenomyomatosis (p = 0.012, metaplasia (p = 0.022 and higher enhanced expressions of iNOS and ROS were detected in Helicobacter pylori infected gallbladder mucosa (p<0.05. CONCLUSIONS: Helicobacter pylori infection in gallbladder mucosa is strongly associated with Helicobacter pylori existed in stomach. Helicobacter pylori is also correlated with gallbladder premalignant lesions including metaplasia and adenomyomatosis. The potential mechanism might be related with higher ROS

  8. Multidimensional effects of biologically synthesized silver nanoparticles in Helicobacter pylori, Helicobacter felis, and human lung (L132) and lung carcinoma A549 cells

    OpenAIRE

    Gurunathan, Sangiliyandi; Jeong, Jae-Kyo; Han, Jae Woong; Zhang, Xi-Feng; Park, Jung Hyun; Kim, Jin-Hoi

    2015-01-01

    Silver nanoparticles (AgNPs) are prominent group of nanomaterials and are recognized for their diverse applications in various health sectors. This study aimed to synthesize the AgNPs using the leaf extract of Artemisia princeps as a bio-reductant. Furthermore, we evaluated the multidimensional effect of the biologically synthesized AgNPs in Helicobacter pylori, Helicobacter felis, and human lung (L132) and lung carcinoma (A549) cells. UV-visible (UV–vis) spectroscopy confirmed the synthesis ...

  9. Sphingomyelin functions as a novel receptor for Helicobacter pylori VacA.

    Directory of Open Access Journals (Sweden)

    Vijay R Gupta

    2008-05-01

    Full Text Available The vacuolating cytotoxin (VacA of the gastric pathogen Helicobacter pylori binds and enters epithelial cells, ultimately resulting in cellular vacuolation. Several host factors have been reported to be important for VacA function, but none of these have been demonstrated to be essential for toxin binding to the plasma membrane. Thus, the identity of cell surface receptors critical for both toxin binding and function has remained elusive. Here, we identify VacA as the first bacterial virulence factor that exploits the important plasma membrane sphingolipid, sphingomyelin (SM, as a cellular receptor. Depletion of plasma membrane SM with sphingomyelinase inhibited VacA-mediated vacuolation and significantly reduced the sensitivity of HeLa cells, as well as several other cell lines, to VacA. Further analysis revealed that SM is critical for VacA interactions with the plasma membrane. Restoring plasma membrane SM in cells previously depleted of SM was sufficient to rescue both toxin vacuolation activity and plasma membrane binding. VacA association with detergent-resistant membranes was inhibited in cells pretreated with SMase C, indicating the importance of SM for VacA association with lipid raft microdomains. Finally, VacA bound to SM in an in vitro ELISA assay in a manner competitively inhibited by lysenin, a known SM-binding protein. Our results suggest a model where VacA may exploit the capacity of SM to preferentially partition into lipid rafts in order to access the raft-associated cellular machinery previously shown to be required for toxin entry into host cells.

  10. Antiadhesive properties of Abelmoschus esculentus (Okra immature fruit extract against Helicobacter pylori adhesion.

    Directory of Open Access Journals (Sweden)

    Jutta Messing

    Full Text Available BACKGROUND: Traditional Asian and African medicine use immature okra fruits (Abelmoschus esculentus as mucilaginous food to combat gastritis. Its effectiveness is due to polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach tissue. The present study investigates the antiadhesive effect in mechanistic detail. METHODOLOGY: A standardized aqueous fresh extract (Okra FE from immature okra fruits was used for a quantitative in vitro adhesion assay with FITC-labled H. pylori J99, 2 clinical isolates, AGS cells, and fluorescence-activated cell sorting. Bacterial adhesins affected by FE were pinpointed using a dot-blot overlay assay with immobilized Lewis(b, sialyl-Lewis(a, H-1, laminin, and fibronectin. (125I-radiolabeled Okra FE polymer served for binding studies to different H. pylori strains and interaction experiments with BabA and SabA. Iron nanoparticles with different coatings were used to investigate the influence of the charge-dependence of an interaction on the H. pylori surface. PRINCIPAL FINDINGS: Okra FE dose-dependently (0.2 to 2 mg/mL inhibited H. pylori binding to AGS cells. FE inhibited the adhesive binding of membrane proteins BabA, SabA, and HpA to its specific ligands. Radiolabeled compounds from FE bound non-specifically to different strains of H. pylori, as well as to BabA/SabA deficient mutants, indicating an interaction with a still-unknown membrane structure in the vicinity of the adhesins. The binding depended on the charge of the inhibitors. Okra FE did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. CONCLUSION: Non-specific interactions between high molecular compounds from okra fruits and the H. pylori surface lead to strong antiadhesive effects.

  11. Helicobacter pylori virulence factors affecting gastric proton pump expression and acid secretion.

    Science.gov (United States)

    Hammond, Charles E; Beeson, Craig; Suarez, Giovanni; Peek, Richard M; Backert, Steffen; Smolka, Adam J

    2015-08-01

    Acute Helicobacter pylori infection of gastric epithelial cells and human gastric biopsies represses H,K-ATPase α subunit (HKα) gene expression and inhibits acid secretion, causing transient hypochlorhydria and supporting gastric H. pylori colonization. Infection by H. pylori strains deficient in the cag pathogenicity island (cag PAI) genes cagL, cagE, or cagM, which do not transfer CagA into host cells or induce interleukin-8 secretion, does not inhibit HKα expression, nor does a cagA-deficient strain that induces IL-8. To test the hypothesis that virulence factors other than those mediating CagA translocation or IL-8 induction participate in HKα repression by activating NF-κB, AGS cells transfected with HKα promoter-Luc reporter constructs containing an intact or mutated NF-κB binding site were infected with wild-type H. pylori strain 7.13, isogenic mutants lacking cag PAI genes responsible for CagA translocation and/or IL-8 induction (cagA, cagζ, cagε, cagZ, and cagβ), or deficient in genes encoding two peptidoglycan hydrolases (slt and cagγ). H. pylori-induced AGS cell HKα promoter activities, translocated CagA, and IL-8 secretion were measured by luminometry, immunoblotting, and ELISA, respectively. Human gastric biopsy acid secretion was measured by microphysiometry. Taken together, the data showed that HKα repression is independent of IL-8 expression, and that CagA translocation together with H. pylori transglycosylases encoded by slt and cagγ participate in NF-κB-dependent HKα repression and acid inhibition. The findings are significant because H. pylori factors other than CagA and IL-8 secretion are now implicated in transient hypochlorhydria which facilitates gastric colonization and potential triggering of epithelial progression to neoplasia.

  12. 氨酚羟考酮与塞来昔布对军队训练伤镇痛的疗效观察%Observation on analgesic effect of oxycodone acetaminophen and celecoxib for military training injury

    Institute of Scientific and Technical Information of China (English)

    张昊聪; 柴伟

    2014-01-01

    Objective To investigate the analgesic effect and safety of oxycodong acetaminophen and celecoxib on the military training injury,and provide a reliable evidence for the usage of drugs. Methods 90 patients were randomly divided into 3 groups(n=30),which were celecoxib group,oxycodone acetaminophen group and placebos group. The efficacy and safety were evaluatedv by the visual analogue score (VAS) before using the drug and the 2nd day,4th day,6th day,8th day after giving drugs. Results The VAS of celecoxib group at each time point were less than that of oxycodong acetaminophen group. And there were nearly no adverse reactions of celecoxib group. The differences were statistically significant (P<0. 05). Conclusion The celecoxib has a good analgesic effect on military training injury and less adverse reactions. Which should be the first choice for paitents suffering from the pain of military training injury.%目的:观察塞来昔布与氨酚羟考酮2种镇痛药物对军队训练伤的镇痛效果以及安全性,为军队训练伤的镇痛用药提供可靠依据。方法将90例训练伤伤员分为3组,每组30例,分别使用塞来昔布、氨酚羟考酮以及安慰剂镇痛,在用药前及用药后第2、4、6、8天进行VAS疼痛评分,观察对比其药物疗效以及安全性。结果塞来昔布在各个时间点的VAS评分均小于氨酚羟考酮组,且不良反应较氨酚羟考酮轻或无,差异均有统计学意义(P<0.05)。结论塞来昔布相比氨酚羟考酮的镇痛作用更为显著,且不良反应少,安全性高,应为军队训练伤镇痛的首选药物。

  13. A Phase II Clinical Trial of Celecoxib Combined with Platinum-Based Regimen as First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer Patients with Cyclooxygenase-2 Positive Expression

    Institute of Scientific and Technical Information of China (English)

    Jun Zhao; Mei-na Wu; Xu-yi Liu; Jie Wang; Zhi-jie Wang; Jian-chun Duan; Qing-zhi Guo; Hua Bai; Lu Yang; Tong-tong An; Xin Wang; Yu-yan Wang

    2009-01-01

    Objective: To evaluate the efficacy and safety of celecoxib plus platinum-doublet as first-line chemotherapy in treatment of advanced non-small cell lung cancer (NSCLC), and to determine the subgroup benefiting from celecoxib combined therapy by molecular analysis. Methods: A total of 44 treatment-naive patients of advanced NSCLC with positive cyclooxygenase-2 (COX-2) expression confirmed by immunohistochemical (IHC) staining were designed to receive celecoxib plus platinum-doublet chemotherapy (cisplatin plus gemcitabine, novelbine or docetaxol) from February 2005 to May 2007. On 5(7 day before chemotherapy, 400 mg celecoxib was administered twice a day orally until obvious evidence of disease progression or intolerable toxicity was found. Adverse events were recorded according to NCI-CTC criteria. The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), 1-year survival rate, response rate (RR) and safety. Additionally, we detected epithelial growth factor receptor (EGFR) status including EGFR gene amplification by real-time PCR and gene mutations by DHPLC followed by sequencing. Results: The response rate was 45% (20/44), and the disease control rate (DCR) was 59% (26/44). The median progression-free survival time and median survival time were 6 m and 18 m, respectively. The 1-year survival rate was 68%. Chemotherapy cycle numbers and best response were found to be the predictive factors for PFS by COX model analysis (P=0.023 and P=0.000, respectively). No factor was found to affect OS. The most common toxicities included neutropenia and nausea/vomit. EGFR gene amplification was an independent prognostic factor influencing OS (P=0.0002). Patients with EGFR mutations (exon 21) had a tendency of disease progression (P=0.041). Conclusion: Encouraging activities of celecoxib combined with platinum-doublet chemotherapy were demonstrated in treatment-naive patients with advanced NSCLC, with good tolerances. For

  14. The extremo-α-carbonic anhydrase from the thermophilic bacterium Sulfurihydrogenibium azorense is highly inhibited by sulfonamides.

    Science.gov (United States)

    Vullo, Daniela; De Luca, Viviana; Scozzafava, Andrea; Carginale, Vincenzo; Rossi, Mosè; Supuran, Claudiu T; Capasso, Clemente

    2013-08-01

    The α-carbonic anhydrase (CA, EC 4.2.1.1) from the newly discovered extremophilic bacterium Sulfurihydrogenibium azorense (SazCA) is the most effective CA known to date. Here we investigated the inhibition profile of this enzyme with a series of aromatic and heterocyclic sulfonamides, and one sulfamate. Many clinically used sulfonamides, such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, celecoxib and sulpiride were low nanomolar/subnanomolar SazCA inhibitors (KIs in the range of 0.9-10.8 nM) whereas simple aromatic derivatives were less effective as SazCA inhibitors. The inhibition profile of SazCA is slightly different from that of the related enzyme from S. yellostonense (SspCA), investigated earlier by our groups. PMID:23777827

  15. The Chemopreventive Effect of Soybean Isoflavones and Celecoxib on DMBA-induced Breast Cancer in Rats%大豆异黄酮和塞来昔布预防大鼠乳腺癌的发生

    Institute of Scientific and Technical Information of China (English)

    杨定勇; 赵之婧; 覃春阳; 杨立民

    2012-01-01

    Objective To observe the chemopreventive effect of soybean isoflavones and celeeoxib on DMBA-chemically induced breast cancer in rats, and explore the mechanisms. Methods A total of 90 rats were randomly divided into 3 groups: DMBA group (control group) , soybean isoflavones group and celecoxib group, each group contained 30 rats. DMBA was intragastrically given to SD female rats to build breast cancer model. Meanwhile, rats in soybean isoflavones group and celecoxib group received soybean isoflavones and celecoxib treatments, respectively. The occurrence rate, latency period, number of breast cancer were observed and analysed. Results The incidence of mammary tumors in soybean isoflavones group (48.28%) and celecoxib group (48.15%) were both lower than that in the DMBA group (79.31%), with statistical difference (P<0.05). The latency periods of mammary tumors in soybean isoflavones group (14.71 ± 1.90 weeks) and celecoxib group (14.46 ± 1.85 weeks) were longer than that in DMBA group (12.96 ± 2.12 weeks) , with statistical difference (P< 0.05). The tumor numbers of soybean isoflavones group (1.79 + 0.80) and celecoxib group (1.62 ±0.77) were less than that of DMBA group (2.43 ±0.99) , with statistical difference (Ρ<0.05). Conclusion Soybean isoflavones and celecoxib could effectively prevent the occurrence of DMBA-induced breast cancer in female rats.%目的 观察大豆异黄酮和塞来昔布对7,12-二甲基苯蒽(7,12-dimethylhenz anthrancene,DMBA)诱发的大鼠乳腺癌形成的影响,并探讨其抗肿瘤机制.方法 90只SD雌大鼠随机分成DMBA组(A组)、DMBA+SOY(B组)组和DMBA+塞来昔布(C组)3组,每组30只.分别给予DMBA油剂灌胃复制大鼠乳腺癌模型,同时B组和C组分别给予含SOY及塞来昔布的饲料喂养至实验结束,观察各组大鼠乳腺癌的发生率、潜伏期及肿瘤数目.结果 B组(48.28%)和C组(48.15%)乳腺癌发生率低于A组(79.31%),差异有统计学意义(P<0.05);B组(14.71±1.90)

  16. Description of Helicobacter valdiviensis sp. nov., an Epsilonproteobacteria isolated from wild bird faecal samples.

    Science.gov (United States)

    Collado, Luis; Jara, Ronald; González, Susana

    2014-06-01

    Two Gram-stain-negative, gently curved rod-shaped isolates (WBE14(T) and WBE19), recovered from wild bird faecal samples in the city of Valdivia (Southern Chile) were subjected to a polyphasic taxonomic study. Results of a genus-specific PCR indicated that these isolates belonged to the genus Helicobacter. This was further confirmed by a phylogenetic analyses based on the 16S rRNA, 60 kDa heat-shock protein (cpn60) and gyrase subunit B (gyrB) genes, where both strains formed a novel phylogenetic line within this genus. The 16S rRNA gene sequence similarity of strain WBE14(T) to the type strains of all other species of the genus Helicobacter examined ranged from 89.4 to 97.0%; Helicobacter brantae and Helicobacter pametensis were the most closely related species. However, on the basis of the protein-coding genes Helicobacter pullorum and Helicobacter canadensis are the most closely related species. These data, together with their different morphological and biochemical characteristics, revealed that these strains represent a novel species, for which the name Helicobacter valdiviensis sp. nov. is proposed, with the type strain WBE14(T) ( = CECT 8410(T) = LMG 27920(T)).

  17. Novel gastric helicobacters and oral campylobacters are present in captive and wild cetaceans.

    Science.gov (United States)

    Goldman, Cinthia G; Matteo, Mario J; Loureiro, Julio D; Almuzara, Marisa; Barberis, Claudia; Vay, Carlos; Catalano, Mariana; Heredia, Sergio Rodríguez; Mantero, Paula; Boccio, Jose R; Zubillaga, Marcela B; Cremaschi, Graciela A; Solnick, Jay V; Perez-Perez, Guillermo I; Blaser, Martin J

    2011-08-26

    The mammalian gastric and oral mucosa may be colonized by mixed Helicobacter and Campylobacter species, respectively, in individual animals. To better characterize the presence and distribution of Helicobacter and Campylobacter among marine mammals, we used PCR and 16S rDNA sequence analysis to examine gastric and oral samples from ten dolphins (Tursiops gephyreus), one killer whale (Orcinus orca), one false killer whale (Pseudorca crassidens), and three wild La Plata river dolphins (Pontoporia blainvillei). Helicobacter spp. DNA was widely distributed in gastric and oral samples from both captive and wild cetaceans. Phylogenetic analysis demonstrated two Helicobacter sequence clusters, one closely related to H. cetorum, a species isolated from dolphins and whales in North America. The second related cluster was to sequences obtained from dolphins in Australia and to gastric non-H. pylori helicobacters, and may represent a novel taxonomic group. Dental plaque sequences from four dolphins formed a third cluster within the Campylobacter genus that likely represents a novel species isolated from marine mammals. Identification of identical Helicobacter spp. DNA sequences from dental plaque, saliva and gastric fluids from the same hosts, suggests that the oral cavity may be involved in transmission. These results demonstrate that Helicobacter and Campylobacter species are commonly distributed in marine mammals, and identify taxonomic clusters that may represent novel species. PMID:21592686

  18. Novel gastric helicobacters and oral campylobacters are present in captive and wild cetaceans.

    Science.gov (United States)

    Goldman, Cinthia G; Matteo, Mario J; Loureiro, Julio D; Almuzara, Marisa; Barberis, Claudia; Vay, Carlos; Catalano, Mariana; Heredia, Sergio Rodríguez; Mantero, Paula; Boccio, Jose R; Zubillaga, Marcela B; Cremaschi, Graciela A; Solnick, Jay V; Perez-Perez, Guillermo I; Blaser, Martin J

    2011-08-26

    The mammalian gastric and oral mucosa may be colonized by mixed Helicobacter and Campylobacter species, respectively, in individual animals. To better characterize the presence and distribution of Helicobacter and Campylobacter among marine mammals, we used PCR and 16S rDNA sequence analysis to examine gastric and oral samples from ten dolphins (Tursiops gephyreus), one killer whale (Orcinus orca), one false killer whale (Pseudorca crassidens), and three wild La Plata river dolphins (Pontoporia blainvillei). Helicobacter spp. DNA was widely distributed in gastric and oral samples from both captive and wild cetaceans. Phylogenetic analysis demonstrated two Helicobacter sequence clusters, one closely related to H. cetorum, a species isolated from dolphins and whales in North America. The second related cluster was to sequences obtained from dolphins in Australia and to gastric non-H. pylori helicobacters, and may represent a novel taxonomic group. Dental plaque sequences from four dolphins formed a third cluster within the Campylobacter genus that likely represents a novel species isolated from marine mammals. Identification of identical Helicobacter spp. DNA sequences from dental plaque, saliva and gastric fluids from the same hosts, suggests that the oral cavity may be involved in transmission. These results demonstrate that Helicobacter and Campylobacter species are commonly distributed in marine mammals, and identify taxonomic clusters that may represent novel species.

  19. Novel epidermal growth factor receptor pathway mediates release of human β-defensin 3 from Helicobacter pylori-infected gastric epithelial cells.

    Science.gov (United States)

    Muhammad, Jibran S; Zaidi, Syed F; Zhou, Yue; Sakurai, Hiroaki; Sugiyama, Toshiro

    2016-04-01

    Persistent Helicobacter pylori (H. pylori) infection in hostile gastric mucosa can result in gastric diseases. Helicobacter pylori induces to express antimicrobial peptides from gastric epithelial cells, especially human β-defensin 3 (hBD3), as an innate immune response, and this expression of hBD3 is mediated by epidermal growth factor receptor (EGFR) activation. In this study, we found that phosphorylation of a serine residue of EGFR via transforming growth factor β-activated kinase-1 (TAK1), and subsequent p38α activation is essential for H. pylori-induced hBD3 release from gastric epithelial cells. We showed that this pathway was dependent on H. pylori type IV secretion system and was independent of H. pylori-derived CagA or peptidoglycan. H. pylori infection induced phosphorylation of serine residue of EGFR, and this phosphorylation was followed by internalization of EGFR; consequently, hBD3 was released at an early phase of the infection. In the presence of TAK1 or p38α inhibitors, synthesis of hBD3 was completely inhibited. Similar results were observed in EGFR-, TAK1- or p38α-knockdown cells. However, NOD1 knockdown in gastric epithelial cells did not inhibit hBD3 induction. Our study has firstly demonstrated that this novel EGFR activating pathway functioned to induce hBD3 at an early phase of H. pylori infection. PMID:26733497

  20. Reflux esophagitis triggered after Helicobacter pylori eradication: a noteworthy demerit of eradication therapy among the Japanese?

    Science.gov (United States)

    Iijima, Katsunori; Koike, Tomoyuki; Shimosegawa, Tooru

    2015-01-01

    In the February 2013 Revision of Insured Medical Treatment, bacterial eradication for all Helicobacter pylori-positive individuals in Japan was covered under the insurance scheme. However, reflux esophagitis is believed to occur in approximately 10% of Japanese patients who undergo eradication therapy. Hence, the risk of reflux esophagitis among such cases should be carefully considered, particularly in the treatment for H. pylori-positive patients who are otherwise healthy. The eradication of H. pylori in cases of H. pylori-positive gastritis markedly suppresses gastric inflammation, and inhibits gastric mucosal atrophy and its progression to intestinal metaplasia. In a long-term follow-up study (10-20 years), eradication treatment was found to reduce the risk of subsequent gastric cancer. However, the fact that eradication-induced reflux esophagitis could increase the long-term risk of Barrett's esophagus and esophageal adenocarcinoma should also be considered in the Japanese population. Appropriate treatment with proton pump inhibitors should be taken into consideration for patients undergoing eradication therapy in clinical practice. PMID:26106373

  1. Destructive effects of butyrate on the cell envelope of Helicobacter pylori.

    Science.gov (United States)

    Yonezawa, Hideo; Osaki, Takako; Hanawa, Tomoko; Kurata, Satoshi; Zaman, Cynthia; Woo, Timothy Derk Hoong; Takahashi, Motomichi; Matsubara, Sachie; Kawakami, Hayato; Ochiai, Kuniyasu; Kamiya, Shigeru

    2012-04-01

    Helicobacter pylori can be found in the oral cavity and is mostly detected by the use of PCR techniques. Growth of H. pylori is influenced by various factors in the mouth, such as the oral microflora, saliva and other antimicrobial substances, all of which make colonization of the oral cavity by H. pylori difficult. In the present study, we analysed the effect of the cell supernatant of a representative periodontal bacterium Porphyromonas gingivalis on H. pylori and found that the cell supernatant destroyed the H. pylori cell envelope. As P. gingivalis produces butyric acid, we focused our research on the effects of butyrate and found that it significantly inhibited the growth of H. pylori. H. pylori cytoplasmic proteins and DNA were detected in the extracellular environment after treatment with butyrate, suggesting that the integrity of the cell envelope was compromised and indicating that butyrate has a bactericidal effect on H. pylori. In addition, levels of extracellular H. pylori DNA increased following treatment with the cell supernatant of butyric acid-producing bacteria, indicating that the cell supernatant also has a bactericidal effect and that this may be due to its butyric acid content. In conclusion, butyric acid-producing bacteria may play a role in affecting H. pylori colonization of the oral cavity. PMID:22194341

  2. Extracellular galectin-3 counteracts adhesion and exhibits chemoattraction in Helicobacter pylori-infected gastric cancer cells.

    Science.gov (United States)

    Subhash, Vinod Vijay; Ling, Samantha Shi Min; Ho, Bow

    2016-08-01

    Galectin-3 (Gal-3) is a β-galactoside lectin that is upregulated and rapidly secreted by gastric epithelial cells in response to Helicobacter pylori infection. An earlier study reported the involvement of H. pylori cytotoxin-associated gene A (cagA) in the expression of intracellular Gal-3. However, the role of extracellular Gal-3 and its functional significance in H. pylori-infected cells remains uncharacterized. Data presented here demonstrate secretion of Gal-3 is an initial host response event in gastric epithelial cells during H. pylori infection and is independent of CagA. Previously, Gal-3 was shown to bind to H. pylori LPS. The present study elaborates the significance of this binding, as extracellular recombinant Gal-3 (rGal-3) was shown to inhibit the adhesion of H. pylori to the gastric epithelial cells. Interestingly, a decrease in H. pylori adhesion to host cells also resulted in a decrease in apoptosis. Furthermore, the study also demonstrated a chemoattractant role of extracellular rGal-3 in the recruitment of THP-1 monocytes. This study outlines the previously unidentified roles of extracellular Gal-3 where it acts as a negative regulator of H. pylori adhesion and apoptosis in gastric epithelial cells, and as a chemoattractant to THP-1 monocytes. Our findings could contribute to the better understanding of how Gal-3 acts as a modulator under H. pylori-induced pathological conditions. PMID:27283429

  3. Genipin-cross-linked fucose-chitosan/heparin nanoparticles for the eradication of Helicobacter pylori.

    Science.gov (United States)

    Lin, Yu-Hsin; Tsai, Shih-Chang; Lai, Chih-Ho; Lee, Che-Hsin; He, Zih Sian; Tseng, Guan-Chin

    2013-06-01

    Helicobacter pylori is a significant human pathogen that recognizes specific carbohydrate receptors, such as the fucose receptor, and produces the vacuolating cytotoxin, which induces inflammatory responses and modulates the cell-cell junction integrity of the gastric epithelium. The clinical applicability of topical antimicrobial agents was needed to complete the eradication of H. pylori in the infected fundal area. In the present study, we combined fucose-conjugated chitosan and genipin-cross-linking technologies in preparing multifunctional genipin-cross-linked fucose-chitosan/heparin nanoparticles to encapsulate amoxicillin of targeting and directly make contact with the region of microorganism on the gastric epithelium. The results show that the nanoparticles effectively reduced drug release at gastric acids and then released amoxicillin in an H. pylori survival situation to inhibit H. pylori growth and reduce disruption of the cell-cell junction protein in areas of H. pylori infection. Furthermore, with amoxicillin-loaded nanoparticles, a more complete H. pylori clearance effect was observed, and H. pylori-associated gastric inflammation in an infected animal model was effectively reduced.

  4. Effect of Helicobacter pylori infection on Bax protein expression in patients with gastric precancerous lesions

    Institute of Scientific and Technical Information of China (English)

    Hai-Feng Liu; Wei-Wen Liu; Guo-An Wang; Xiao-Chun Teng

    2005-01-01

    AIM: To investigate the effect of Helicobacter pylori (H pylori) infection on Bax protein expression, and explore the role of H pylori in gastric carcinogenesis.METHODS: H pylori was assessed by rapid urease test and Warthin-Starry method, and expression of Bax protein was examined immunohistochemically in 72 patients with pre-malignant lesions.RESULTS: Bax protein was differently expressed in intestinal metaplasia and gastric dysplasia, and showed 63.99% positivity. The positivity of Bax protein expression in H pylori-positive gastric precancerous lesions (72.3%) was significantly higher than that in H pylori-negative gastric precancerous lesions (48.0%, χ2 = 4.191, P<0.05).H pylori infection was well correlated with the expression of Bax protein in gastric precancerous lesions (r = 0.978,P<0.01). After eradication of H pylori, the positivity of Bax protein expression significantly decreased in H pylori-positive gastric precancerous lesions (χ2= 5.506,P<0.05). In the persisting H pylori-infected patients,the positivity of Bax protein expression was not changed.CONCLUSION: H pylori infection may be involved in the upregulation of Bax gene, which might be one of the mechanisms of H pylori infection-induced gastric epithelial cell apoptosis. H pylori might act as a tumor promoter in the genesis of gastric carcinoma and eradication of H pylori could inhibit gastric carcinogenesis.

  5. In vitro and In vivo Anti-Helicobacter pylori Activities of Centella asiatica Leaf Extract

    Science.gov (United States)

    Zheng, Hong-Mei; Choi, Myung-Joo; Kim, Jae Min; Lee, Kye Wan; Park, Yu Hwa; Lee, Don Haeng

    2016-01-01

    Helicobacter pylori infection is associated with an increased risk of developing upper gastrointestinal tract diseases. However, treatment failure is a major cause of concern mainly due to possible recurrence of infection, the side effects, and resistance to antibiotics. The aim of this study was to investigate the activities of Centella asiatica leaf extract (CAE) against H. pylori both in vitro and in vivo. The minimum inhibitory concentrations (MICs) against 55 clinically isolated strains of H. pylori were tested using an agar dilution method. The MICs of CAE ranged from 0.125 mg/mL to 8 mg/mL, effectiveness in inhibiting H. pylori growth was 2 mg/mL. The anti-H. pylori effects of CAE in vivo were also examined in H. pylori-infected C57BL/6 mice. CAE was orally administrated once daily for 3 weeks at doses of 50 mg/kg and 250 mg/kg. CAE at the 50 mg/kg dose significantly reduced H. pylori colonization in mice gastric mucosa. Our study provides novel insights into the therapeutic effects of CAE against H. pylori infection, and it suggests that CAE may be useful as an alternative therapy. PMID:27752495

  6. The immunomodulatory properties of Helicobacter pylori confer protection against allergic and chronic inflammatory disorders

    Directory of Open Access Journals (Sweden)

    Anne eMüller

    2012-02-01

    Full Text Available Chronic infection with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes carriers to a high risk of developing gastric and duodenal ulcers, gastric cancer and gastric lymphoma, but has also recently been shown to protect against certain allergic and chronic inflammatory disorders. The immunomodulatory properties that allow the bacteria to persist for decades in infected individuals in the face of a vigorous, yet ultimately non-protective, innate and adaptive immune response may at the same time confer protection against allergies, asthma and inflammatory bowel diseases. Experimental evidence from mouse models suggests that H. pylori has evolved to skew the adaptive immune response towards immune tolerance rather than immunity, which promotes persistent infection on the one hand, and inhibits auto-aggressive and allergic T-cell responses on the other. Regulatory T-cells mediating peripheral immune tolerance have emerged as key cellular players in facilitating persistent infection as well as protection from allergies, in both observational studies in humans and experimental work in mice. Recent data suggest that H. pylori actively targets dendritic cells to promote tolerance induction. The findings discussed in this review raise the possibility of harnessing the immunomodulatory properties of H. pylori for the prevention and treatment of allergic and auto-immune diseases, and also provide new insights relevant for H. pylori-specific vaccine development.

  7. Anti-Helicobacter pylori activity and immunostimulatory effect of extracts from Byrsonima crassa Nied. (Malpighiaceae

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    Vilegas Wagner

    2009-01-01

    Full Text Available Abstract Background Several in vitro studies have looked at the effect of medicinal plant extracts against Helicobacter pylori (H. pylori. Regardless of the popular use of Byrsonima crassa (B. crassa as antiemetic, diuretic, febrifuge, to treat diarrhea, gastritis and ulcers, there is no data on its effects against H. pylori. In this study, we evaluated the anti-H. pylori of B. crassa leaves extracts and its effects on reactive oxygen/nitrogen intermediates induction by murine peritoneal macrophages. Methods The minimal inhibitory concentration (MIC was determined by broth microdilution method and the production of hydrogen peroxide (H2O2 and nitric oxide (NO by the horseradish peroxidase-dependent oxidation of phenol red and Griess reaction, respectively. Results The methanolic (MeOH and chloroformic (CHCl3 extracts inhibit, in vitro, the growth of H. pylori with MIC value of 1024 μg/ml. The MeOH extract induced the production H2O2 and NO, but CHCl3 extract only NO. Conclusion Based in our results, B. crassa can be considered a source of compounds with anti-H. pylori activity, but its use should be done with caution in treatment of the gastritis and peptic ulcers, since the reactive oxygen/nitrogen intermediates are involved in the pathogenesis of gastric mucosal injury induced by ulcerogenic agents and H. pylori infections.

  8. Streptococcus mitis induces conversion of Helicobacter pylori to coccoid cells during co-culture in vitro.

    Directory of Open Access Journals (Sweden)

    Yalda Khosravi

    Full Text Available Helicobacter pylori (H. pylori is a major gastric pathogen that has been associated with humans for more than 60,000 years. H. pylori causes different gastric diseases including dyspepsia, ulcers and gastric cancers. Disease development depends on several factors including the infecting H. pylori strain, environmental and host factors. Another factor that might influence H. pylori colonization and diseases is the gastric microbiota that was overlooked for long because of the belief that human stomach was a hostile environment that cannot support microbial life. Once established, H. pylori mainly resides in the gastric mucosa and interacts with the resident bacteria. How these interactions impact on H. pylori-caused diseases has been poorly studied in human. In this study, we analyzed the interactions between H. pylori and two bacteria, Streptococcus mitis and Lactobacillus fermentum that are present in the stomach of both healthy and gastric disease human patients. We have found that S. mitis produced and released one or more diffusible factors that induce growth inhibition and coccoid conversion of H. pylori cells. In contrast, both H. pylori and L. fermentum secreted factors that promote survival of S. mitis during the stationary phase of growth. Using a metabolomics approach, we identified compounds that might be responsible for the conversion of H. pylori from spiral to coccoid cells. This study provide evidences that gastric bacteria influences H. pylori physiology and therefore possibly the diseases this bacterium causes.

  9. ETHNIC AND POPULATION-SPECIFIC FEATURES OF SOME IMMUNOLOGICAL PARAMETERS IN CHRONIC HELICOBACTER PYLORI INFECTION

    Directory of Open Access Journals (Sweden)

    E. S. Ageeva

    2012-01-01

    Full Text Available Abstract. Immunophenotype profile of lymphocytes (CD3+, CD4+ and CD8+ from peripheral blood in gastric ulcer associated with Helicobacter pylori, chronic gastritis and stomach cancer has been studied in Khakassian aboriginals and migrants. Apoptosis of peripheral blood lymphocytes was also evaluated. Some alterations of immunological indexes were revealed in patients infected with Helicobacter pylori, as compared to healthy donors and migrants. The changes were characterized by a more intense apoptotic death of lymphocytes in the patients, when compared with numbers of apoptotic cells in control group. Probable role of apoptotic events in regulation of local and system immunity in Helicobacter pylori infection is discussed.

  10. Helicobacter ganmani sp nov., a urease-negative anaerobe isolated from the intestines of laboratory mice

    DEFF Research Database (Denmark)

    Robertson, B.R.; O'Rourke, J.L.; Vandamme, P.;

    2001-01-01

    Spiral bacteria were isolated from the intestines of laboratory mice during a study examining the presence of Helicobacter species and other spiral organisms naturally infecting mice maintained at four different animal facilities in Sydney, Australia. One group of 17 isolates, cultured from mice...... from three of the four facilities, were found to be helicobacters but did not fall within any of the 18 currently recognized species. These isolates were unusual in that they only grew anaerobically at 37 degreesC and were incapable of growth under microaerobic conditions. Like Helicobacter rodentium...

  11. Helicobacter species and common gut bacterial DNA in gallbladder with cholecystitis

    Institute of Scientific and Technical Information of China (English)

    Peren; H; Karagin; Unne; Stenram; Torkel; Wadstrm; sa; Ljungh

    2010-01-01

    AIM:To analyze the association between Helicobacter spp. and some common gut bacteria in patients with cholecystitis. METHODS:A nested-polymerase chain reaction (PCR), specif ic to 16S rRNA of Helicobacter spp. was performed on paraff in-embedded gallbladder samples of 100 cholecystitis and 102 control cases. The samples were also analyzed for some common gut bacteria by PCR. Positive samples were sequenced for species identif ication. RESULTS: Helicobacter DNA was found in seven out of 100 cases of acute a...

  12. Helicobacter pylori and non-malignant upper gastrointestinal diseases.

    Science.gov (United States)

    Vasapolli, Riccardo; Malfertheiner, Peter; Kandulski, Arne

    2016-09-01

    Peptic ulcer disease (PUD) has been further decreased over the last decades along with decreasing prevalence of Helicobacter pylori-associated PUD. A delayed H. pylori eradication has been associated with an increased risk of rehospitalization for complicated recurrent peptic ulcer and reemphasized the importance of eradication especially in patients with peptic ulcer bleeding (PUB). PUB associated with NSAID/aspirin intake and H. pylori revealed an additive interaction in gastric pathophysiology which favors the "test-and-treat" strategy for H. pylori in patients with specific risk factors. The H. pylori-negative and NSAID-negative "idiopathic PUD" have been increasingly observed and associated with slower healing tendency, higher risk of recurrence, and greater mortality. Helicobacter pylori-associated dyspepsia has been further investigated and finally defined by the Kyoto consensus. Helicobacter pylori eradication therapy is advised as first option in this group of patients. Only in the case of symptom persistence or recurrence after eradication therapy, dyspeptic patients should be classified as functional dyspepsia (FD). There were few new data in 2015 on the role of H. pylori infection in gastroesophageal reflux disease (GERD), and in particular Barrett's esophagus. A lower prevalence of gastric atrophy with less acid output in patients with erosive esophagitis confirmed previous findings. In patients with erosive esophagitis, no difference was observed in healing rates neither between H. pylori-positive and H. pylori-negative patients nor between patients that underwent eradication therapy compared to patients without eradication. These findings are in line with the current consensus guidelines concluding that H. pylori eradication has no effects on symptoms and does not aggravate preexisting GERD. PMID:27531536

  13. Helicobacter pylori in Cholecystectomy Specimens-Morphological and Immunohistochemical Assessment

    Science.gov (United States)

    Reddy, Venkatarami; Jena, Amitabh; Gavini, Siva; Thota, Asha; Nandyala, Rukamangadha; Chowhan, Amit Kumar

    2016-01-01

    Introduction Helicobacter pylori (H.pylori) is associated with gastritis, peptic ulcer, gastric carcinoma and gastric lymphoma. Current literature describes presence of H.pylori in various extra-gastric locations and its association with many diseases. Apart from the conventional location of gastric and duodenal mucosa, H.pylori have been isolated and cultured from gallbladder. Aim Analysis of cholecystectomy specimens to detect H.pylori by means of immunohistochemical staining. Materials and Methods There were a total of 118 cholecystectomy specimens received in the Department of Pathology in three months duration. We have performed immunostaining for H.pylori in 45 consecutive cases of cholecystectomy specimen. Clinical and other investigational information were retrieved from the medical records department. For each case, routine Haematoxylin and Eosin stain was studied. Immunohistochemistry (IHC) was done using purified polyclonal Helicobacter pylori antiserum. Results Majority of the patients had undergone laparoscopic cholecystectomy for the presenting complaint of right hypochondrial pain. Multiple pigmented stones were present in majority (27/45) of them. Immunostain for H.pylori was positive in ten cases. Six of these cases had pigmented gall stones, two had stones not specified and in two of the cases there were no stones. Conclusion Helicobacter pylori is present in gall bladder and is commonly seen in association with stones. A more detailed study of cholecystectomy cases (both neoplastic and non-neoplastic) with serological, culture and molecular data of H.pylori is desirable to study the pathogenesis of cholecystitis, its association with gall stones and other gall bladder disorders. PMID:27437221

  14. Helicobacter pylori and non-malignant upper gastrointestinal diseases.

    Science.gov (United States)

    Vasapolli, Riccardo; Malfertheiner, Peter; Kandulski, Arne

    2016-09-01

    Peptic ulcer disease (PUD) has been further decreased over the last decades along with decreasing prevalence of Helicobacter pylori-associated PUD. A delayed H. pylori eradication has been associated with an increased risk of rehospitalization for complicated recurrent peptic ulcer and reemphasized the importance of eradication especially in patients with peptic ulcer bleeding (PUB). PUB associated with NSAID/aspirin intake and H. pylori revealed an additive interaction in gastric pathophysiology which favors the "test-and-treat" strategy for H. pylori in patients with specific risk factors. The H. pylori-negative and NSAID-negative "idiopathic PUD" have been increasingly observed and associated with slower healing tendency, higher risk of recurrence, and greater mortality. Helicobacter pylori-associated dyspepsia has been further investigated and finally defined by the Kyoto consensus. Helicobacter pylori eradication therapy is advised as first option in this group of patients. Only in the case of symptom persistence or recurrence after eradication therapy, dyspeptic patients should be classified as functional dyspepsia (FD). There were few new data in 2015 on the role of H. pylori infection in gastroesophageal reflux disease (GERD), and in particular Barrett's esophagus. A lower prevalence of gastric atrophy with less acid output in patients with erosive esophagitis confirmed previous findings. In patients with erosive esophagitis, no difference was observed in healing rates neither between H. pylori-positive and H. pylori-negative patients nor between patients that underwent eradication therapy compared to patients without eradication. These findings are in line with the current consensus guidelines concluding that H. pylori eradication has no effects on symptoms and does not aggravate preexisting GERD.

  15. Genotypes of Helicobacter pylori in patients with peptic ulcer bleeding

    Institute of Scientific and Technical Information of China (English)

    Chin-Lin Perng; Hwai-Jeng Lin; Wen-Ching Lo; Guan-Ying Tseng; I-Chen Sun; Yueh-Hsing Ou

    2004-01-01

    AIM: Helicobacter pyloricauses chronic gastritis, peptic ulcer,gastric cancer and MALT-lymphoma. Different genotypes of Helicobacter pylori are confirmed from diverse geographic areas. Its association with bleeding peptic ulcer remains controversial. The aim of this study was to investigate the Helicobacter pylori vac4 alleles, cagA and iceA in patients with bleeding peptic ulcer.METHODS: We enrolled patients with bleeding, nonbleeding peptic ulcers and chronic gastritis. Biopsy specimens were obtained from the antrum of the stomach for rapid urease test, bacterial culture and PCR assay. DNA extraction and polymerase chain reaction were used to detect the presence or absence of cagA and to assess the polymorphism of vac4 and iceA.RESULTS: A total of 168 patients (60.4%) (25 patients with chronic gastritis, 26 patients with bleeding gastric ulcer,51 patients with non-bleeding gastric ulcer, 26 patients with bleeding duodenal ulcer, and 40 patients with non-bleeding duodenal ulcer) were found to have positive PCR results between January 2001 and December 2002. Concerning genotypes, we found cagA (139/278, 50%), vacA s1a (127/278, 45.7%), and iceA1 (125/278, 45%) predominated in all studied patients. In patients with bleeding peptic ulcers,vac4 s1a and m1T were fewer than those in patients with non-bleeding peptic ulcers (37/106 vs69/135, P=0.017, and 4/106 vs21/135, P=0.002).CONCLUSION: In patients with peptic ulcers, Hpylori vacA s1a and m1T prevent bleeding complication.

  16. Epidemiology of Helicobacter pylori: transmission, translocation and extragastric reservoirs.

    Science.gov (United States)

    Nabwera, H M; Logan, R P

    1999-12-01

    Although H. pylori infection is endemic and despite more than 10 years of research, the mode and route of transmission remain elusive. This may, in part, be due to the inherent problems of detecting H. pylori noninvasively. The prevalence of infection varies between countries and is closely related to Growth Domestic Product. An age-cohort effect and data from longitudinal studies suggest that the incidence of infection is much higher in children than adults. In developing countries the prevalence of infection is often more than 80% in young adults, in contrast to less than 10% for similar age groups in developed countries. The observations of mosaicism (in the VacA gene) and a panmycytic population structure imply exchange of genetic material either in or outside of the host, which is supported by the increasing recognition of polyclonal infection and suggests that secondary infection occurs after primary acquisition. In addition, in children persistent primary infection may sometimes occur only after previous (repeated) exposure and/or transient colonisation of the gastric mucosa. H. pylori and other gastric Helicobacter spp are always noninvasive, but other human nongastric Helicobacter spp have sometimes been isolated from the systemic circulation in immunocompromised patients. For nonhuman hosts, intestinal Helicobacter spp are thought to translocate more frequently from the colon to the liver. Within the human host, the oral cavity is the principal extragastric reservoir, although case reports suggest that H. pylori may sometimes be found beyond the 2nd part of the duodenum. The hypothesis that H. pylori is a zoonosis or transmitted as coccoid forms by a vector (pets, houseflies) is not supported by recent research showing that H. pylori is entirely unable to support an aerobic or anaerobic metabolism and that coccoid forms are non-viable. H. pylori is primarily acquired in infancy, most probably via the oroorogastric route, from other family members or close

  17. Helicobacter pylori and gastric acid: an intimate and reciprocal relationship

    Science.gov (United States)

    Waldum, Helge L.; Kleveland, Per M.; Sørdal, Øystein F.

    2016-01-01

    Helicobacter pylori (Hp) is the main cause of gastritis, peptic ulcer disease and gastric cancer. There are still unanswered questions related to the interaction between Hp and man, like what determines the susceptibility for the initial infection and the mechanisms for the carcinogenic effect. The initial infection seems to require a temporal gastric hypoacidity. For Hp to survive in the gastric mucous layer, some acidity is necessary. Hp itself is probably not directly carcinogenic. Only when inducing oxyntic mucosal inflammation and atrophy with hypoacidity, Hp predisposes for gastric cancer. Gastrin most likely plays a central role in the Hp pathogenesis of duodenal ulcer and gastric cancer.

  18. [Eradication therapy of antibiotic-resistant strains of Helicobacter pylori].

    Science.gov (United States)

    Shcherbakov, P L; Belousova, N L; Shcherbakova, M Iu; Kashnikov, V S

    2010-01-01

    Treatment of inflammatory diseases of the upper digestive tract, associated with Helicobacter pylori has recently greatly complicated by the presence of significant number of resistant strains of this microorganism to traditionally used drugs for eradication therapy. Average resistance to metronidazole and clarithromycin in Russia is about 30 and 25% respectively. The article presents the experience of treating patients with metronidazole resistant strains of H. pylori with using triple therapy, which included a drug used nitrofurans--nifuroxazide in suspension, proton pump inhibitors and clarithromycin. PMID:21485525

  19. Inflammation, immunity, and vaccines for Helicobacter pylori infection.

    Science.gov (United States)

    Velin, Dominique; Straubinger, Kathrin; Gerhard, Markus

    2016-09-01

    The tight control of the innate and adaptive immune responses in the stomach mucosa during chronic Helicobacter pylori infection is of prime importance for the bacteria to persist and for the host to prevent inflammation-driven diseases. This review summarizes recent data on the roles of innate and adaptive immune responses during H. pylori/host interactions. In addition, the latest preclinical developments of H. pylori vaccines are discussed with a special focus on the clinical trial reported by Zeng et al., who provided evidence that oral vaccination significantly reduces the acquisition of natural H. pylori infection in children. PMID:27531535

  20. Relationship of Halitosis with Gastric Helicobacter Pylori Infection

    OpenAIRE

    Farnaz HajiFattahi; Maryam Hesari; Homayoun Zojaji; Fatemeh Sarlati

    2015-01-01

    Objectives: Gastric infection with Helicobacter pylori may be one of the main causes of halitosis. This study was performed to evaluate the relationship of Heli- cobacter pylori infection with halitosis.Materials and Methods: This case control study was performed on 44 dyspeptic patients with a mean age of 34.29±13.71 years (range 17 to 76 years). The case group included 22 patients with halitosis and no signs of diabetes mellitus, renal or liver failure, upper respiratory tract infection, ma...

  1. An Overview of Helicobacter pylori VacA Toxin Biology

    OpenAIRE

    Nora J. Foegeding; Caston, Rhonda R.; McClain, Mark S.; Ohi, Melanie D.; Cover, Timothy L.

    2016-01-01

    The VacA toxin secreted by Helicobacter pylori enhances the ability of the bacteria to colonize the stomach and contributes to the pathogenesis of gastric adenocarcinoma and peptic ulcer disease. The amino acid sequence and structure of VacA are unrelated to corresponding features of other known bacterial toxins. VacA is classified as a pore-forming toxin, and many of its effects on host cells are attributed to formation of channels in intracellular sites. The most extensively studied VacA ac...

  2. Chemotaxis plays multiple roles during Helicobacter pylori animal infection

    OpenAIRE

    Terry, K; S. M. Williams; Connolly, L.; Ottemann, K M

    2005-01-01

    Helicobacter pylori is a human gastric pathogen associated with gastric and duodenal ulcers as well as specific gastric cancers. H. pylori infects approximately 50% of the world's population, and infections can persist throughout the lifetime of the host. Motility and chemotaxis have been shown to be important in the infection process of H. pylori. We sought to address the specific roles of chemotaxis in infection of a mouse model system. We found that mutants lacking cheW, cheA, or cheY are ...

  3. [Helicobacter pylori in the development of dental caries].

    Science.gov (United States)

    Moseeva, M V; Belova, E V; Vakhrushev, Ia M

    2010-01-01

    It is shown, that in patients with erosive and ulcer defects of gastroduodenal zone at settling Helicobacter pylori (Hp) in an oral cavity in 100% of cases caries develops at intensity 13.6 +/- 1.4 teeth. Produced Hp protease and ammonia cause disintegration connected to protein silica acids and reduce activity lysocim, worsening, thus, fluid and protective properties of a saliva. In the subsequent infringement of autopurification of a teeth results in accumulation of a dental strike where protease activity conditionally pathogenic microflora conducts to depolymerization and demineralization enamels of a teeth. PMID:20496804

  4. Oral and Gastric Helicobacter Pylori: Effects and Associations

    OpenAIRE

    Nélio Veiga; Carlos Pereira; Carlos de Resende; Odete Amaral; Manuela Ferreira; Paula Nelas; Claudia Chaves; João Duarte; Luis Cirnes; José Carlos Machado; Paula Ferreira; Correia, Ilídio J.

    2015-01-01

    Introduction This study consisted in the comparison of the prevalence of Helicobacter pylori (H. pylori) present in the stomach and in saliva of a sample of Portuguese adolescents and the assessment of the association between H. pylori infection with socio-demographic variables and prevalence of dental caries. Materials and Methods A cross-sectional study was designed including a sample of 447 adolescents aged 12 to 19 years old, attending a public school in Sátão, Portugal. A questionnaire a...

  5. [Helicobacter pylori in the development of dental caries].

    Science.gov (United States)

    Moseeva, M V; Belova, E V; Vakhrushev, Ia M

    2010-01-01

    It is shown, that in patients with erosive and ulcer defects of gastroduodenal zone at settling Helicobacter pylori (Hp) in an oral cavity in 100% of cases caries develops at intensity 13.6 +/- 1.4 teeth. Produced Hp protease and ammonia cause disintegration connected to protein silica acids and reduce activity lysocim, worsening, thus, fluid and protective properties of a saliva. In the subsequent infringement of autopurification of a teeth results in accumulation of a dental strike where protease activity conditionally pathogenic microflora conducts to depolymerization and demineralization enamels of a teeth.

  6. Regulation of Helicobacter pylori adherence by gene conversion

    OpenAIRE

    Talarico, Sarah; Whitefield, Shawn E.; Fero, Jutta; Haas, Rainer; Salama, Nina R.

    2012-01-01

    Genetic diversification of Helicobacter pylori adhesin genes may allow adaptation of adherence properties to facilitate persistence despite host defenses. The sabA gene encodes an adhesin that binds sialyl-Lewis antigens on inflamed gastric tissue. We found variability in the copy number and locus of the sabA gene and the closely related sabB and omp27 genes due to gene conversion among 51 North American pediatric H. pylori strains. We determined that sabB to sabA gene conversion is predomina...

  7. Helicobacter pylori Infection and atherosclerosis: a systematic review.

    Directory of Open Access Journals (Sweden)

    Reza Karbasi-Afshar

    2015-02-01

    Full Text Available Helicobacter pylori (H. pylori is a spiral-shaped gram negative bacterium that naturally colonizes the human gastric epithelium. In recent years, large evidence has come to the literature strongly proposing causal link between H. pylori and extra gastric disorders. Cardiovascular system is one of the extra gastric organs that can be affected by H. pylori infection. The first evidence suggestive of such an association comes from seroepidemiological evaluations, but histopathological and eradication studies have strongly confirmed existence of a causal association between H. pylori infection and cardiovascular events.

  8. One-week triple therapy for eradication of helicobacter pylori

    International Nuclear Information System (INIS)

    Objective: The optimum therapy for Helicobacter pylori infection is yet to be defined in Pakistan despite a high prevalence of helicobacter associated diseases in this community. The most popular and effective regimen was therefore chosen among the currently recommended combinations used worldwide to document its efficacy in our symptomatic Helicobacter positive dyspeptic patients. Design: It was a prospective, non-randomized study. Place and duration of Study: The study lasted from January 1998 till June 1999 at the Postgraduate Institute, Government Lady Reading Hospital and Fauji Foundation Hospital, Peshawar. Subjects and Methods: Consecutive dyspeptic patients with peptic ulcer disease as well as non ulcer dyspepsia with a positive H. pylori status on histology from the specimens obtained from the antral region of the stomach, who consented to take part in the study were enrolled. They were given omeprazole 20 mg bd, clarithromycin 500 mg bd. And amoxycillin 1 gm bd for one week. One group comprised patients with confirmed peptic ulcer disease while the second group comprised patients with macroscopic/microscopic antral gastritis. Patients with peptic ulcer disease were given additional course of omerprazol for another 4 weeks to ensure healing of their ulcers. All patients were re scoped after stopping all drugs and their H. pylori status re-assessed on histology. Results: A total of 84 patients consented to enter the study. Fifty-nine were males and twenty-five were females. Fifty-eight patients completed the study while others were lost followup. There were no dropouts due to side effects of the drugs. Sixteen patients had peptic ulcer disease while 68 had macroscopic/microscopic active antral gastric only. The Helicobacter pylori eradication has been successful in only 12 patients giving a cure rate of 20.60% as determined per protocol analysis. The eradication rates were disappointingly low in both groups. Conclusion: The results are extremely

  9. The Multiple Carbohydrate Binding Specificities of Helicobacter pylori

    Science.gov (United States)

    Teneberg, Susann

    Persistent colonization of the human stomach by Helicobacter pylori is a risk factor for the development of peptic ulcer disease and gastric cancer. Adhesion of microbes to the target tissue is an important determinant for successful initiation, establishment and maintenance of infection, and a variety of different candidate carbohydrate receptors for H. pylori have been identified. Here the different the binding specifities, and their potential role in adhesion to human gastric epithelium are described. Finally, recent findings on the roles of sialic acid binding SabA adhesin in interactions with human neutrophils and erythrocytes are discussed.

  10. Adherence of Helicobacter pylori to the Gastric Mucosa

    Directory of Open Access Journals (Sweden)

    Marguerite Clyne

    1997-01-01

    Full Text Available Bacterial adhesion to the intestinal epithelium is a critical initial step in the pathogenesis of many enteric diseases. Helicobacter pylori is a duodenal pathogen that adheres to the gastric epithelium and causes gastritis and peptic ulceration. The mechanism by which H pylori causes disease has not yet been elucidated but adherence to the gastric mucosa is thought to be an important virulence determinant of the organism. What is known about adherence of H pylori to the gastric mucosa is summarized. Topics discussed are the mechanism of H pylori adherence; in vitro and in vivo models of H pylori infection; and adherence and potential adhesins and receptors for H pylori.

  11. Age-dependent eradication of Helicobacter pylori in Japanese patients

    Institute of Scientific and Technical Information of China (English)

    Satoshi; Mamori; Akihiro; Higashida; Fumiaki; Kawara; Katsuhiro; Ohnishi; Akihiko; Takeda; Eri; Senda; Cho; Ashida; Hajime; Yamada

    2010-01-01

    AIM:To determine the general risk factors affecting the failure rate of first-line eradication therapy in Japanese patients with Helicobacter pylori(H.pylori)infection.METHODS:The present study enrolled 253 patients who had an H.pylori infection,underwent gastroendoscopy,and were treated with H.pylori eradication therapy.Eradication therapy consisted of 30 mg lansoprazole plus 750 mg amoxicillin and 400 mg clarithromycin twice daily for 7 d.All of the patients underwent a 13 C urea breath test at least 1 mo...

  12. [Peptic Ulcer Disease Associated with Helicobacter pylori Infection].

    Science.gov (United States)

    Yeo, Se-Hwan; Yang, Chang-Hun

    2016-06-25

    Although the global prevalence of peptic ulcer disease (PUD) is decreasing, PUD is still one of the most common upper gastrointestinal diseases in the world due to Helicobacter pylori infection and increased use of non-steroidal anti-inflammatory drugs. In Korea, the prevalence of H. pylori infection is also declining, but it is still the major cause of PUD. The outcomes of H. pylori infection are caused by imbalances between bacterial virulence factors, host factors, and environmental influences. In this review, we describe the prevalence trends of H. pylori infection in Korea, the mechanism of H. pylori infection-related PUD, and treatment strategies.

  13. Solid Phospholipid Dispersions for Oral Delivery of Poorly Soluble Drugs: Investigation Into Celecoxib Incorporation and Solubility-In Vitro Permeability Enhancement.

    Science.gov (United States)

    Fong, Sophia Yui Kau; Martins, Susana M; Brandl, Martin; Bauer-Brandl, Annette

    2016-03-01

    Celecoxib (CXB) is a Biopharmaceutical Classification System class II drug in which its oral bioavailability is limited by poor aqueous solubility. Although a range of formulations aiming to increase the solubility of CXB have been developed, it is not completely understood, whether (1) an increase in CXB solubility leads to a subsequent increase in permeability across intestinal barrier and (2) the presence of bile salts affects the solubility and permeability behavior of CXB formulations. By formulating CXB solid phospholipid (PL) dispersions with various PL-to-drug ratios using freeze drying, the present study illustrated that the enhancement of CXB solubility was not proportionally translated into enhanced permeability; both parameters were highly dependent on the PL-to-drug ratios as well as the dispersion media (i.e., the presence of 3-mM sodium taurocholate). This study highlights the importance of evaluating both, solubility and permeability, and the use of biorelevant medium for testing the candidate-enabling performance of liposomal formulations. Mechanisms at molecular level that may explain the effect of PL formulations on the permeability of CXB are also discussed. PMID:26886329

  14. Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate

    Directory of Open Access Journals (Sweden)

    João P. Costa-Nunes

    2015-01-01

    Full Text Available Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day and dicholine succinate (50 mg/kg/day, against standard antidepressants, imipramine (7 mg/kg/day and citalopram (15 mg/kg/day, utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies.

  15. Design, Synthesis, and Evaluation of an (18)F-Labeled Radiotracer Based on Celecoxib-NBD for Positron Emission Tomography (PET) Imaging of Cyclooxygenase-2 (COX-2).

    Science.gov (United States)

    Kaur, Jatinder; Tietz, Ole; Bhardwaj, Atul; Marshall, Alison; Way, Jenilee; Wuest, Melinda; Wuest, Frank

    2015-10-01

    A series of novel fluorine-containing cyclooxygenase-2 (COX-2) inhibitors was designed and synthesized based on the previously reported fluorescent COX-2 imaging agent celecoxib-NBD (3; NBD=7-nitrobenzofurazan). In vitro COX-1/COX-2 inhibitory data show that N-(4-fluorobenzyl)-4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide (5; IC50 =0.36 μM, SI>277) and N-fluoromethyl-4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide (6; IC50 =0.24 μM, SI>416) are potent and selective COX-2 inhibitors. Compound 5 was selected for radiolabeling with the short-lived positron emitter fluorine-18 ((18) F) and evaluated as a positron emission tomography (PET) imaging agent. Radiotracer [(18) F]5 was analyzed in vitro and in vivo using human colorectal cancer model HCA-7. Although radiotracer uptake into COX-2-expressing HCA-7 cells was high, no evidence for COX-2-specific binding was found. Radiotracer uptake into HCA-7 tumors in vivo was low and similar to that of muscle, used as reference tissue. PMID:26287271

  16. Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate.

    Science.gov (United States)

    Costa-Nunes, João P; Cline, Brandon H; Araújo-Correia, Margarida; Valença, Andreia; Markova, Natalyia; Dolgov, Oleg; Kubatiev, Aslan; Yeritsyan, Naira; Steinbusch, Harry W M; Strekalova, Tatyana

    2015-01-01

    Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day) delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day) and dicholine succinate (50 mg/kg/day), against standard antidepressants, imipramine (7 mg/kg/day) and citalopram (15 mg/kg/day), utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies. PMID:26064929

  17. Combination therapy versus celecoxib, a single selective COX-2 agent, to reduce gastrointestinal toxicity in arthritic patients: patient and cost-effectiveness considerations

    Directory of Open Access Journals (Sweden)

    Scolnik M

    2011-08-01

    Full Text Available Marina Scolnik1, Gurkirpal Singh21Sección Reumatología, Servicio de Clínica Médica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; 2Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, Palo Alto, CA, USAAbstract: Nonsteroidal anti-inflammatory drugs (NSAIDs are widely used for treating symptoms of rheumatologic diseases, such as osteoarthritis and rheumatoid arthritis. Knowing their side effects and the way to minimize them is a medical responsibility. To reduce NSAID-related risk, clinicians should choose a gastroprotective strategy. This may include coprescribing a traditional NSAID with a proton pump inhibitor or a high-dose histamine 2-receptor antagonist (H2RA, or using a cyclo-oxygenase (COX-2 selective inhibitor or a COX-2 with a proton pump inhibitor. Assessing each patient's risk (cardiovascular and gastrointestinal is a priority in order to decide the best intervention to minimize toxicity. In this article, we review some of the common interventions for reducing the gastrointestinal side effects of NSAIDs.Keywords: arthritis, osteoarthritis, celecoxib, nonsteroidal anti-inflammatory drugs, gastrointestinal toxicity, cost-effectiveness

  18. Determination of Antibiotic Resistance and Synergistic Effect of Multiple Antibiotics on Helicobacter Pylori Isolated from the Stomach Ulcer Biopsy Specimens

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    Habibi Nava, F. (MSc

    2014-06-01

    Full Text Available Background and Objective: Resistance of Helicobacter Pylori (H. pylori to antibiotics is the main cause of relapse into Helcobacterial infections. With the use of several antibiotics that have synergistic effect, we can inhibit this antibiotic resistance. Thus, we aimed at determining resistance patterns and assessing the synergy of combining multiple antibiotics on H. pylori. Material and Methods: Biopsy specimens were taken from 100 patients with gastric ulcer referred to Imam Reza hospital in Amol, north of Iran. After isolation and identification of H. Pylori, antibiogram was performed with different antibiotic disks containing one antibiotic, a combination of two antibiotics (metronidazole + clarithromycin and three antibiotics (metronidazole + Claritromycin + Ciprofloxacin. Results: In this study, H. pylori were isolated from 53 (53% biopsy specimens. Of these, 49 (5.92% were resistant to metronidazole, 14 (26% to amoxicillin, 10 (19% to clarithromycin, 7 (13% to tetracycline, 13 (5/24% to furazolidone and 7 (13% to ciprofloxacin. In survey of synergistic effect, an increase in inhibition zone diameter around of combined disks was seen up to 5mm compared to the most effective antibiotic. Conclusion: The inhibition zone diameter of discs containing two and three antibiotics was large, in comparison with one antibiotic. Key words: H. Pylori; Antibiotic Resistance; Synergy Effect

  19. Narrow-spectrum inhibitors targeting an alternative menaquinone biosynthetic pathway of Helicobacter pylori.

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    Yamamoto, Tsuyoshi; Matsui, Hidenori; Yamaji, Kenzaburo; Takahashi, Tetsufumi; Øverby, Anders; Nakamura, Masahiko; Matsumoto, Atsuko; Nonaka, Kenichi; Sunazuka, Toshiaki; Ōmura, Satoshi; Nakano, Hirofumi

    2016-09-01

    We aimed to identify narrow-spectrum natural compounds that specifically inhibit an alternative menaquinone (MK; vitamin K2) biosynthetic pathway (the futalosine pathway) of Helicobacter pylori. Culture broth samples of 6183 microbes were examined using the paper disc method with different combinations of 2 of the following 3 indicator microorganisms: Bacillus halodurans C-125 and Kitasatospora setae KM-6054(T), which have only the futalosine pathway of MK biosynthesis, and Bacillus subtilis H17, which has only the canonical MK biosynthetic pathway. Most of the active compounds isolated from culture broth samples were from the families of polyunsaturated fatty acids (PUFAs). Only one compound isolated from the culture broth of Streptomyces sp. K12-1112, siamycin I (a 21-residue lasso peptide antibiotic), targeted the futalosine pathway. The inhibitory activities of representative PUFAs and siamycin I against the growth of B. halodurans or K. setae were abrogated by supplementation with MK. Thereafter, the growth of H. pylori strains SS1 and TN2GF4 in broth cultures was dose-dependently suppressed by eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or siamycin I, and these inhibitory effects were reduced by supplementation with MK. Daily administration of EPA (100 μM), DHA (100 μM), or siamycin I (2.5 μM) in drinking water reduced the H. pylori SS1 colonization in the gastric mucosa of C57BL/6 mice by 96%, 78%, and 68%, respectively. These data suggest that EPA, DHA, and siamycin I prevented H. pylori infection by inhibiting the futalosine pathway of MK biosynthesis. PMID:27346378

  20. Helicobacter spp. in the saliva, stomach, duodenum and faeces of colony dogs.

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    Ekman, E; Fredriksson, M; Trowald-Wigh, G

    2013-01-01

    The role of Helicobacter spp. infection in canine gastrointestinal disease is unclear and routes of transmission are of epidemiological and zoonotic importance. The aim of this study was to identify Helicobacter spp. in the saliva, stomach, duodenum and faeces of dogs using a multiplex PCR, and to evaluate any attendant histopathological changes. Helicobacter canis was the most common species detected in saliva and faeces and no correlation between the presence of Helicobacter spp. and histopathological changes in either the stomach or duodenum was observed. All dogs examined were co-infected with up to four species of the organism. This is the first time these bacteria have been studied at species level at multiple sites within the canine alimentary tract. PMID:22683393