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  1. Arsenic Trioxide Injection

    Science.gov (United States)

    Arsenic trioxide is used to treat acute promyelocytic leukemia (APL; a type of cancer in which there ... worsened following treatment with other types of chemotherapy. Arsenic trioxide is in a class of medications called ...

  2. Resveratrol and arsenic trioxide act synergistically to kill tumor cells in vitro and in vivo.

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    Xiao-Yan Zhao

    Full Text Available BACKGROUND AND AIMS: Arsenic trioxide (As2O3, which used as an effective agent in the treatment of leukaemia and other solid tumors, is largely limited by its toxicity. QT prolongation, torsades de pointes and sudden heart death have been implicated in the cardiotoxicity of As2O3. The present study was designed to explore whether the combination of As2O3 and resveratrol could generate a more powerful anti-cancer effect both in vitro and in vivo. MATERIALS AND METHODS: MTT assay was performed to assess the proliferation of Hela, MCF-7 and NB4 cells. Isobolographic analysis was used to evaluate combination index values from cell viability data. The apoptosis and the cellular reactive oxygen species (ROS level were assessed by fluorescent microscopy and flow cytometry separately in vitro. The effect of As2O3, alone and in combination with resveratrol on Hela tumor growth in an orthotopic nude mouse model was also investigated. The tumor volume and the immunohistochemical analysis of CD31, CD34 and VEGF were determined. RESULTS: Resveratrol dramatically enhanced the anti-cancer effect induced by As2O3 in vitro. In addition, isobolographic analysis further demonstrated that As2O3 and resveratrol generated a synergistic action. More apoptosis and ROS generation were observed in the combination treatment group. Similar synergistic effects were found in nude mice in vivo. The combination of As2O3 and resveratrol dramatically suppressed both tumor growth and angiogenesis in nude mice. CONCLUSIONS: Combining As2O3 with resveratrol would be a novel strategy to treat cancer in clinical practice.

  3. Arsenic trioxide exerts synergistic effects with cisplatin on non-small cell lung cancer cells via apoptosis induction

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    Zhang Yawei

    2009-08-01

    Full Text Available Abstract Background Despite multidisciplinary treatment, lung cancer remains a highly lethal disease due to poor response to chemotherapy. The identification of therapeutic agents with synergistic effects with traditional drugs is an alternative for lung cancer therapy. In this study, the synergistic effects of arsenic trioxide (As2O3 with cisplatin (DDP on A549 and H460 non-small cell lung cancer (NSCLC cells were explored. Methods A549 and H460 human lung cancer cells were treated with As2O3 and/or DDP. Cell growth curves, cell proliferation, cell cycle, and apoptosis of human cancer cell lines were determined by the 3-(4,5-dimethylthiahiazo (-z-y1-3,5-di-phenytetrazoliumromide (MTT method, clonogenic assay, and flow cytometry (FCM. Apoptosis was further assessed by TUNEL staining. Cell cycle and apoptosis related protein p21, cyclin D1, Bcl-2, bax, clusterin, and caspase-3 were detected by western blot. Results MTT and clonogenic assay showed As2O3 within 10-2 μM to 10 μM exerted inhibition on the proliferation of NSCLC cells, and 2.5 μM As2O3 exerted synergistic inhibition on proliferation with 3 μg/ml DDP. The combination indices (CI for A549 and H460 were 0.5 and 0.6, respectively, as confirmed by the synergism of As2O3 with DDP. FCM showed As2O3 did not affect the cell cycle. The G0/G1 fraction ranged from 57% to 62% for controlled A549 cells and cells treated with As2O3 and/or DDP. The G0/G1 fraction ranged from 37% to 42% for controlled H460 cells and cells treated with As2O3 and/or DDP. FCM and TUNEL staining illustrated that the combination of As2O3 and DDP provoked synergistic effects on apoptosis induction based on the analysis of the apoptosis index. Western blotting revealed that the expression of cell cycle related protein p21 and cyclin D1 were not affected by the treatments, whereas apoptosis related protein bax, Bcl-2, and clusterin were significantly regulated by As2O3 and/or DDP treatments compared with controls. The

  4. Synergistic Apoptosis-Inducing Antileukemic Effects of Arsenic Trioxide and Mucuna macrocarpa Stem Extract in Human Leukemic Cells via a Reactive Oxygen Species-Dependent Mechanism

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    Kuan-Hung Lu; Hui-Ju Lee; Min-Li Huang; Shang-Chih Lai; Yu-Ling Ho; Yuan-Shiun Chang; Chin-Wen Chi

    2012-01-01

    The objective of this study was to examine the potential of enhancing the antileukemic activity of arsenic trioxide (ATO) by combining it with a folk remedy, crude methanolic extract of Mucuna macrocarpa (CMEMM). Human leukemia cells HL-60, Jurkat, and Molt-3 were treated with various doses of ATO, CMEMM, and combinations thereof for 24 and 48 h. Results indicated that the combination of 2.5  μ M ATO and 50  μ g/mL CMEMM synergistically inhibited cell proliferation in HL-60 and Jurkat cell li...

  5. Synergistic Apoptosis-Inducing Antileukemic Effects of Arsenic Trioxide and Mucuna macrocarpa Stem Extract in Human Leukemic Cells via a Reactive Oxygen Species-Dependent Mechanism

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    Kuan-Hung Lu

    2012-01-01

    Full Text Available The objective of this study was to examine the potential of enhancing the antileukemic activity of arsenic trioxide (ATO by combining it with a folk remedy, crude methanolic extract of Mucuna macrocarpa (CMEMM. Human leukemia cells HL-60, Jurkat, and Molt-3 were treated with various doses of ATO, CMEMM, and combinations thereof for 24 and 48 h. Results indicated that the combination of 2.5 μM ATO and 50 μg/mL CMEMM synergistically inhibited cell proliferation in HL-60 and Jurkat cell lines. Apoptosis triggered by ATO/CMEMM treatment was confirmed by accumulation of cells in the sub-G1 phase in cell cycle analyses, characteristic apoptotic nuclear fragmentation, and increased percentage of annexin V-positive apoptotic cells. Such combination treatments also led to elevation of reactive oxygen species (ROS. The antioxidants N-acetyl cysteine (NAC, butylated hydroxytoluene, and α-tocopherol prevented cells from ATO/CMEMM-induced apoptosis. The ATO/CMEMM-induced activation of caspase-3 and caspase-9 can be blocked by NAC. In summary, these results suggest that ATO/CMEMM combination treatment exerts synergistic apoptosis-inducing effects in human leukemic cells through a ROS-dependent mechanism and may provide a promising antileukemic approach in the future.

  6. Synergistic effect of all-trans-retinoic acid and arsenic trioxide on growth inhibition and apoptosis in human hepatoma, breast cancer, and lung cancer cells in vitro

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    Le-Min Lin; Bao-Xin Li; Jian-Bing Xiao; Dan-Hua Lin; Bao-Feng Yang

    2005-01-01

    AIM: To investigate the effect of all-trans-retinoic acid (ATRA) on arsenic trioxide (As2O3)-induced apoptosis of human hepatoma, breast cancer, and lung cancer cells in an attempt to find a better combination therapy for solid tumors.METHODS: Human hepatoma cell lines HepG2, Hep3B,human breast cancer cell line MCF-7, and human lung adenocarcinoma cell line AGZY-83-a were treated with As2O3 together with ATRA. Cell survival fraction was determined by MTT assay, cell viability and apoptosis were measured by annexin V-fluorescein isothiocyanate (FITC) and PI staining, and intracellular glutathione (GSH)and glutathione-S-transferase (GST) activities were determined using commercial kits.RESULTS: Cytotoxicity of ATRA was low. ATRA (0.1, 1,and 10 μmol/L) could synergistically potentiate As2O3 to exert a dose-dependent inhibition of growth and to induce apoptosis in each of the cell lines. HepG2 and Hep3B with low intracellular GSH or GST activities were remarkably sensitive to As2O3 or As2O3+ATRA, while AGZY-83-a with higher GSH or GST activities was less sensitive to As2O3or As2O3+ATRA. Treatment with 2 μmol/L As2O3 for 72 h significantly decreased intracellular GSH and GST levels in each of the cell lines, and 1 μmol/L ATRA alone reduced minimal intracellular GSH and GST levels. ATRA potentiated the effect of As2O3 on intracellular GSH levels, but intracellular GST levels were not significantly affected by the combination of As2O3 and ATRA for 72 h as compared to As2O3 alone.CONCLUSION: ATRA can strongly potentiate As2O3-induced growth-inhibition and apoptosis in each of the cell lines, and two drugs can produce a significant synergic effect. The sensitivity to As2O3 or As2O3+ATRA is inversely proportional to intracellular GSH or GST levels in each of the cell lines. The GSH redox system may be the possible mechanism by which ATRA synergistically potentiates As2O3 to exert a dose-dependent inhibition of growth and to induce apoptosis.

  7. Oral arsenic trioxide poisoning and secondary hazard from gastric content.

    Science.gov (United States)

    Kinoshita, Hidenori; Hirose, Yasuo; Tanaka, Toshiharu; Yamazaki, Yoshihiko

    2004-12-01

    In a suicide attempt, a 54-year-old man ingested arsenic trioxide. Gastric lavage was performed, but most of the poison remained as a mass in his stomach. A total gastrectomy was also performed to avoid intestinal perforation and arsenic poisoning. After the operation, he developed ventricular fibrillation. At one point, his circulation recovered spontaneously, but he later died from refractory circulatory failure. Many medical staff members were exposed to fumes from the patient's stomach. Some of the staff were diagnosed with corneal erosion or laryngitis. Because arsenic trioxide reacts with acid to produce arsine, the symptoms experienced by medical staff are directly attributable to arsine produced as a result of the reaction of arsenic trioxide with gastric acid. This case highlights the need for the introduction of protective measures to safeguard medical staff from exposure to arsine gas during the treatment of patients poisoned from ingested arsenic trioxide.

  8. Arsenic trioxide: an ancient drug revived

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    ZHOU Jin

    2012-01-01

    Objective To summarize the clinical applications of arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL),as well as non-APL malignancies and to discuss the mechanisms and adverse effects involved in ATO administration.Data sources The data in this article were collected from PubMed and CHKD database with relevant English and Chinese articles published from 1957 to 2011,with key words including acute promyelocytic leukemia,arsenic trioxide,treatment,and mechanism.Study selection Articles including any information about ATO in the treatment of APL were selected.Results APL is a rare subtype of acute myeloid leukemia,with dismal prognosis under treatment with traditional chemotherapy.ATO impressively increases the complete remission rate and prolongs survival of patients with APL,with only mild and transient adverse effects.The advances in the understanding of multiple mechanisms involved in ATO treatment will benefit more cancers in future.Conclusion Deeper understanding of mechanisms involved in ATO treatment may provide rationales for future clinical applications in a number of human malignancies.Chin Med J 2012; 125( 19):3556-3560

  9. Arsenic trioxide negatively affects Echinococcus granulosus.

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    Wang, Bo; Jiang, Yufeng; Wang, Zhuo; Li, Fangfang; Xing, Guoqiang; Peng, Xinyu; Zhang, Shijie; Lv, Hailong

    2015-11-01

    Spillage of cyst contents during surgery is the major cause of recurrences of hydatidosis, also called cystic echinococcosis (CE). Currently, many scolicidal agents are used for inactivation of the cyst contents. However, due to complications in the use of those agents, new and more-effective treatment options are urgently needed. The aim of this study was to investigate the in vitro efficacy of arsenic trioxide (ATO) against Echinococcus granulosus protoscolices. Protoscolices of E. granulosus were incubated in vitro with 2, 4, 6, and 8 μmol/liter ATO; viability of protoscolices was assessed daily by microscopic observation of movements and 0.1% eosin staining. A small sample from each culture was processed for scanning and transmission electron microscopy. ATO demonstrated a potent ability to kill protoscolices, suggesting that ATO may represent a new strategy in treating hydatid cyst echinococcosis. However, the in vivo efficacy and possible side effects of ATO need to be explored.

  10. Arsenic trioxide: safety issues and their management

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    Wing-Yan AU; Yok-Lam KWONG

    2008-01-01

    Arsenic trioxide (As2O3) has been used medicinally for thousands of years.Its therapeutic use in leukaemia was described a century ago.Recent rekindling in the interest of As2O3 is due to its high efficacy in acute promyelocytic leukaemia (APL).As2O3 has also been tested clinically in other blood and solid cancers.Most studies have used intravenous As2O3,although an oral As2O3 is equally efficacious.Side effects of As2O3 are usually minor,including skin reactions,gastrointestinal upset,and hepatitis.These respond to symptomatic treatment or temporary drug cessation,and do not compromise subsequent treatment with As2O3.During induction therapy in APL,a leucocytosis may occasionally occur,which can be associated with fluid accumulation and pulmonary infiltration.The condition is similar to the APL differentiation syndrome during treatment with all-trans retinoic acid,and responds to cytoreductive treatment and corticosteroids.Intravenous As2O3 treatment leads to QT prolongation.In the presence of under-lying cardiopulmonary diseases or electrolyte disturbances,particularly hypokalaemia and hypomagnesaemia,serious arrhythmias may develop,with torsades du pointes reported in 1% of cases.This may be related to a dose-dependent arsenic-mediated inhibition of potassium ion channels that compro-mises cardiac repolarization.Because of slow intestinal absorption,oral-As2O3 gives a lower plasma arsenic concentration,which is associated with lesser QT prolongation and hence a more favorable cardiac safety profile.As2O3 does not appear to enter the central nervous system.However,if the blood brain barrier is breached,elemental arsenic may enter the cerebrospinal fluid.As2O3 is predomi-nantly excreted in the kidneys,and dose adjustment is required when renal func-tion is impaired.

  11. Inhibition factors of arsenic trioxide therapeutic effects in patients with acute promyelocytic leukemia

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    Sui Meijuan; Zhang Zhuo; Zhou Jin

    2014-01-01

    Objective To summarize limitations involved in arsenic trioxide therapeutic effects in acute promyelocytic leukemia,because current studies show that some individuals of acute promyelocytic leukemia have relatively poor outcomes during treatment with arsenic trioxide.Data sources Most relevant articles were included in the PubMed database between 2000 and 2013 with the keywords "acute promyelocytic leukemia","arsenic trioxide","thiol" or "methylation".In addition,a few older articles were also reviewed.Study selection Data and articles related to arsenic trioxide effect in acute promyelocytic leukemia treatment were selected and reviewed.We developed an overview of limitations associated with arsenic trioxide therapeutic effect.Results This review focuses on the researches about the arsenic trioxide therapeutic effect in acute promyelocytic leukemia and summarizes three mainly limitations which can influence the arsenic trioxide therapeutic effect to different degrees.First,with the combination of arsenic and glutathione the therapeutic effect and cytotoxicity decrease when glutathione concentration increases; second,arsenic methylation,stable arsenic methylation products weaken the apoptosis effect of arsenic trioxide in leukemia cells; third,gene mutations affect the sensitivity of tumor cells to arsenic trioxide and increase the resistance of leukemia cells to arsenic trioxide.Conclusions The chief limitations are listed in the review.If we can exclude all of them,we can obtain a better therapeutic effect of arsenic trioxide in patients with acute promyelocytic leukemia.

  12. Comparing two arsenic trioxide administration methods in APL therapy

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    周晋; 孟然; 杨宝峰

    2004-01-01

    @@ Arsenic trioxide (As2O3) was approved for the treatment of acute promyelocytic leukemia (APL) and was under investigation for other malignancies. However, some side effects occurred during APL treatment with routine As2O3 infusion. We tried a ' continuously slow As2O3 intravenous infusion ' method and assessed its effectiveness and security in APL treatment.

  13. Hepatoprotective efficacy of curcumin against arsenic trioxide toxicity

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    VV Mathews; P Binu; MV Sauganth Paul; M Abhilash; Alex Manju; R Harikumaran Nair

    2012-01-01

    Objective: To evaluate the efficacy of curcumin in combating arsenic induced hepatic oxidative stress, histopathological changes and the hepatic arsenic accumulation in rat model. Methods:Oxidative stress was induced by oral administration 4 mg/kg b.wt of arsenic trioxide (As2O3,) for 45 days in experimental rats. The level of liver arsenic concentration, lipid peroxidation, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione-S-transferase (GST), and glutathione peroxidase (GPx) were determined in adult male Wistar rats. Hepatotoxicity was assessed by quantifying the aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phophatase (ALP). Hepatoprotective efficacy of curcumin (15 mg/kg b.wt) was evaluated by combination treatment with As2O3. Results: As2O3 administration leads to the generation of reactive oxygen species (ROS), arsenic accumulation, serum marker enzymes release and decrease in antioxidant enzymes in liver. Retention of arsenic in liver caused increased level of lipid peroxidation with a concomitant decline in the glutathione dependant antioxidant enzymes and antiperoxidative enzymes. Curcumin treatment protected the liver from arsenic induced deterioration of antioxidant levels as well as oxidative stress. And also a significant decrease in hepatic arsenic accumulation and serum marker enzymes was observed. Histopathological examination revealed a curative improvement in liver tissue. Conclusions:These findings lead to the conclusion that curcumin may have the potential to protect the liver from arsenic-induced toxic effects.

  14. Tetramethylpyrazine potentiates arsenic trioxide activity against HL-60 cell lines

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    Wu, Yuni; Xu, Youhua; Shen, Yali; Wang, Cuicui; Guo, Gaili; Hu, Tiantian [Key Laboratory of Developmental Diseases in Childhood, Chongqing (China); Key Laboratory of Pediatrics in Chongqing, Chongqing (China); Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing (China)

    2012-02-17

    The objective of this study was to evaluate the effects of tetramethylpyrazine (TMP) in combination with arsenic trioxide (As{sub 2}O{sub 3}) on the proliferation and differentiation of HL-60 cells. The HL-60 cells were treated with 300 µg/mL TMP, 0.5 µM As{sub 2}O{sub 3}, and 300 µg/mL TMP combined with 0.5 µM As{sub 2}O{sub 3}, respectively. The proliferative inhibition rates were determined with MTT. Differentiation was detected by the nitroblue tetrazolium (NBT) reduction test, Wright's staining and the distribution of CD11b and CD14. Flow cytometry was used to analyze cell cycle distribution. RT-PCR and Western blot assays were employed to detect the expressions of c-myc, p27, CDK2, and cyclin E1. Combination treatment had synergistic effects on the proliferative inhibition rates. The rates were increased gradually after the combination treatment, much higher than those treated with the corresponding concentration of As{sub 2}O{sub 3} alone. The cells exhibited characteristics of mature granulocytes and a higher NBT-reducing ability, being a 2.6-fold increase in the rate of NBT-positive ratio of HL-60 cells within the As{sub 2}O{sub 3} treatment versus almost a 13-fold increase in the TMP + As{sub 2}O{sub 3} group. Cells treated with both TMP and As{sub 2}O{sub 3} expressed far more CD11b antigens, almost 2-fold compared with the control group. Small doses of TMP potentiate As{sub 2}O{sub 3}-induced differentiation of HL-60 cells, possibly by regulating the expression and activity of G0/G1 phase-arresting molecules. Combination treatment of TMP with As{sub 2}O{sub 3} has significant synergistic effects on the proliferative inhibition of HL-60 cells.

  15. Arsenic Trioxide Modulates DNA Synthesis and Apoptosis in Lung Carcinoma Cells

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    Kenneth Ndebele

    2010-04-01

    Full Text Available Arsenic trioxide, the trade name Trisenox, is a drug used to treat acute promyleocytic leukemia (APL. Studies have demonstrated that arsenic trioxide slows cancer cells growth. Although arsenic influences numerous signal-transduction pathways, cell-cycle progression, and/or apoptosis, its apoptotic mechanisms are complex and not entirely delineated. The primary objective of this research was to evaluate the effects of arsenic trioxide on DNA synthesis and to determine whether arsenic-induced apoptosis is mediated via caspase activation, p38 mitogen–activated protein kinase (MAPK, and cell cycle arrest. To achieve this goal, lung cancer cells (A549 were exposed to various concentrations (0, 2, 4, 6, 8, and 10 µg/mL of arsenic trioxide for 48 h. The effect of arsenic trioxide on DNA synthesis was determined by the [3H]thymidine incorporation assay. Apoptosis was determined by the caspase-3 fluorescein isothiocyanate (FITC assay, p38 MAP kinase activity was determined by an immunoblot assay, and cell-cycle analysis was evaluated by the propidium iodide assay. The [3H]thymidine-incorporation assay revealed a dose-related cytotoxic response at high levels of exposure. Furthermore, arsenic trioxide modulated caspase 3 activity and induced p38 MAP kinase activation in A549 cells. However, cell-cycle studies showed no statistically significant differences in DNA content at subG1 check point between control and arsenic trioxide treated cells.

  16. 活细胞实时成像技术研究抗坏血酸(AA)协同砷剂抗人骨肉瘤MG-63的体外疗效%The synergistic effect of MG-63 cells treated with ascorbic acid (AA) and arsenic trioxide in vitro by using continuous live cell imaging and analysis platform (cell IQ)

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    黄晓春; 李泽兵; 陈增淦; 陈统一; 王玲燕

    2012-01-01

    Objective To study the synergistic effect of human osteosarcoma cell line MG-63 treated with ascorbic acid (AA) and arsenic trioxide (As2O3) in vitro. Methods We used continuous live cell imaging and analysis platform (cell IQ) to observe cell proliferation and morphologic change of MG-63 cells which were treated with AA (62. 5 /nmol/L) and As2O3 (1 jumol/L) alone or together . Results MG-63 cell proliferation was depressed observed when treated by A A (62. 5 fimol/L) and As2O3 (1 jumol/L) independently. The effect of AA (62. 5 μmol/L) plus As2O3 (1 /imol/L) was synergistic, which further inhibits MG-63 cell proliferation. Conclusions The treatment of AA combined with As2O3 can induce synergistic effect on the depression of MG-63 cell proliferation. This result provides a new pathway and basic reaserch data of treating osteosarcoma in clinical practice.%目的 研究抗坏血酸(ascorbic acid,AA)和三氧化二砷(arsenic trioxide,As2O3)抗人骨肉瘤细胞MG-63的体外疗效.方法 以MG-63细胞为体外模型,用62.5 μmol/L AA与1μmol/L As2O3单独或联合处理细胞,利用新型连续活细胞图像采集和分析平台(continuous live cell imaging and analysis platform,Cell IQ)实时观察细胞的生长情况和形态学的变化.结果 1 μmol/L As2O3和62.5 μmol/L AA单独处理都可抑制MG-63细胞的生长并诱导细胞死亡.1 μmol/L As2O3和62.5 μmol/L AA联合处理细胞较单独处理组细胞抑制效果更明显.结论 AA和AS2O3抗人骨肉瘤细胞Mg-63可起到协同作用,这一结果为临床治疗骨肉瘤提供了新的思路和实验依据.

  17. The effect of arsenic trioxide on human hepatoma cell line BEL-7402 culturedin vitro

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    You Lin Yang; Hong Yu Xu; Yuan Yuan Gao; Qiao Li Wu; Guang Qiang Gao

    2000-01-01

    AIM To study the effect of a wide range of concentration of arsenic trioxide on human hepatoma cell lineBEL-7402 and its mechanism.METHODS The BEL-7402 cells were treated with arsenic trioxide (a final concentration of 0.5, 1 and2 μmol/L, respectively) in various durations or for 4 successive days. The cell growth and proliferation wereobserved by cell counting and cell-growth curve. Morphologic changes were studied under electronmicroscopy. Flow cytometry was used to assay cell-DNA distribution and the protein expression of Bcl-2 andBax was detected by immunocytochemical method.RESULTS The cell growth was significantly inhibited by the different concentrations of arsenic trioxide asrevealed by cell counting and cell-growth curve. Arsenic trioxide treatment at 0.5, 1 and 2 μmol/L, resultedin a sub-G1 cell peak. The decreased G0/G1 phase cell and the increased percentage of S phase cell were observed by flow cytometer, suggesting that the inhibiting effect of arsernic trioxide on BEL-7402 cell lay inG0/G1 phase cell. Apoptotis-related morphology, such as intact cell membrane, nucleic condensation,apoptotic body formation, can be seen under the electron microscopy. High protein expression level of Bcl-2and Bax was detected in 1 and 2 μmol/L arsenic trioxide-treated cells, but that of Bax was more significant.Arsenic trioxide treatment at 0.5 μmol/L resulted in higher expression level of Bcl-2 and lower expressionlevel of Bax compared with control (P1<0.01, P2<0.01).CONCLUSION Arsenic trioxide not only inhibited the proliferation but also induced apoptosis of humanhepatoma cell line BEL-7402. The induced-apoptosis effect of 1 and 2 μmol/L arsenic trioxide was relative tothe expression level of Bcl-2 and Bax.

  18. Arsenic species excretion after dimercaptopropanesulfonic acid (DMPS) treatment of an acute arsenic trioxide poisoning

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    Heinrich-Ramm, R. [Ordinariat fuer Arbeitsmedizin der Universitaet Hamburg und Zentralinstitut fuer Arbeitsmedizin, Hamburg (Germany); Schaller, K.H.; Angerer, J. [Institut und Poliklinik fuer Arbeits-, Sozial- und Umweltmedizin der Universitaet Erlangen-Nuernberg, Schillerstr. 25, 91054 Erlangen (Germany); Horn, J. [Medizinische Klinik II, Toxikologische-internistische Intensivstation, Klinikum Nuernberg, Nuernberg (Germany)

    2003-02-01

    We studied the urinary excretion of the different arsenic species in urine samples from a young man who tried to commit suicide by ingesting about 0.6 g arsenic trioxide. He received immediate therapy with dimercaptopropanesulfonic acid (DMPS) after his delivery into the hospital. We assessed urinary arsenite (inorganic trivalent arsenic), arsenate (inorganic pentavalent arsenic), pentavalent dimethylarsinic acid (DMA) and pentavalent monomethylarsonic acid (MMA) in urine with ion-exchange chromatography and on-line hydride-technique atomic absorption spectrometry. The predominant amount of the excreted arsenic was unchanged trivalent inorganic arsenic (37.4%), followed by pentavalent inorganic arsenic (2.6%), MMA (2.1%), DMA (0.2%) and one unidentified arsenic species (0.7%, if calculated as DMA). In the first urine voiding in the clinic, the total arsenic concentration was 215 mg/l, which fell 1000-fold after 8 days of DMPS therapy. A most striking finding was the almost complete inhibition of the second methylation step in arsenic metabolism. As mechanisms for the reduced methylation efficiency, the saturation of the enzymatic process of arsenic methylation, the high dosage of antidote DMPS, which might inhibit the activity of the methyl transferases, and analytical reasons are discussed. The high dosage of DMPS is the most likely explanation. The patient left the hospital after a 12-day treatment with antidote. (orig.)

  19. Severe acute axonal neuropathy following treatment with arsenic trioxide for acute promyelocytic leukemia: a case report

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    Marcus Kuhn

    2016-05-01

    Full Text Available Peripheral neuropathy is a common complication of arsenic toxicity. Symptoms are usually mild and reversible following discontinuation of treatment. A more severe chronic sensorimotor polyneuropathy characterized by distal axonal-loss neuropathy can be seen in chronic arsenic exposure. The clinical course of arsenic neurotoxicity in patients with coexistence of thiamine deficiency is only anecdotally known but this association may potentially lead to severe consequences. We describe a case of acute irreversible axonal neuropathy in a patient with hidden thiamine deficiency who was treated with a short course of arsenic trioxide for acute promyelocytic leukemia. Thiamine replacement therapy and arsenic trioxide discontinuation were not followed by neurological recovery and severe polyneuropathy persisted at 12-month follow-up. Thiamine plasma levels should be measured in patients who are candidate to arsenic trioxide therapy. Prophylactic administration of vitamin B1 may be advisable. The appearance of polyneuropathy signs early during the administration of arsenic trioxide should prompt electrodiagnostic testing to rule out a pattern of axonal neuropathy which would need immediate discontinuation of arsenic trioxide.

  20. The role of Akt on Arsenic trioxide suppression of 3T3-L1 preadipocyte differentiation

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    Zhi Xin WANG; Chun Sun JIANG; Lei LIU; Xiao Hui WANG; Hai Jing JIN; Qiao WU; Quan CHEN

    2005-01-01

    The present study investigates the molecular details of how arsenic trioxide inhibits preadipocyte differentiation and examines the role of Akt/PKB in regulation of differentiation and apoptosis. Continual exposure of arsenic trioxide, at the clinic achievable dosage that does not induce apoptosis, suppressed 3T3-L1 cell differentiation into fat cells by inhibiting the expression of PPARγ and C/EBPα and disrupting the interaction between PPARγ and RXRα, which determines the programming of the adipogenic genes. Interestingly, if we treated the cells for 12 or 24 h and then withdrew arsenic trioxide, the cells were able to differentiate to the comparable levels of untreated cells as assayed by the activity of GAPDH, the biochemical marker of preadipocyte differentiation. Long term treatment blocked the differentiation and the activity of GAPDH could not recover to the comparable levels of untreated cells. Continual exposure of arsenic trioxide caused accumulation in G2/M phase and the accumulation of p21. We found that arsenic trioxide induced the expression and the phosphorylation of Akt/PKB and it inhibited the interaction between Akt/PKB and PPARγ. Akt/PKB inhibitor appears to block the arsenic trioxide suppression of differentiation. Our results suggested that Akt/PKB may play a role in suppression of apoptosis and negatively regulate preadipocyte differentiation.

  1. Torsades de pointes in 3 patients with leukemia treated with arsenic trioxide.

    Science.gov (United States)

    Unnikrishnan, D; Dutcher, J P; Varshneya, N; Lucariello, R; Api, M; Garl, S; Wiernik, P H; Chiaramida, S

    2001-03-01

    Arsenic trioxide is used in clinical trials in the treatment of relapsed and resistant cases of acute promyelocytic leukemia. Adverse effects from arsenic in these studies have been multisystemic. Arsenic is known to cause corrected QT-interval prolongation and T-wave changes, but the potential for serious ventricular arrhythmias is less well understood. Torsades de pointes, a form of ventricular tachycardia, has been reported with arsenic poisoning but not at therapeutic doses used in protocols for hematologic malignancies. We describe 3 patients in whom this arrhythmia developed while they were treated with arsenic trioxide. Early recognition of the arrhythmia or correction of contributory factors is important because arsenic induced ventricular arrhythmias are known to be resistant to most chemical methods and electrical cardioversion.

  2. Protective effect of resveratrol on arsenic trioxide-induced nephrotoxicity in rats

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    Zhang, Weiqian; Liu, Yan; Ge, Ming; Jing, Jiang; Chen, Yan; Jiang, Huijie; Yu, Hongxiang; Li, Ning; Zhang, Zhigang

    2014-01-01

    BACKGROUD/OBEJECTIVES Arsenic, which causes human carcinogenicity, is ubiquitous in the environment. This study was designed to evaluate modulation of arsenic induced cancer by resveratrol, a phytoalexin found in vegetal dietary sources that has antioxidant and chemopreventive properties, in arsenic trioxide (As2O3)-induced Male Wistar rats. MATERIALS/METHODS Adult rats received 3 mg/kg As2O3 (intravenous injection, iv.) on alternate days for 4 days. Resveratrol (8 mg/kg) was administered (iv...

  3. ARSENIC TRIOXIDE DOWNREGULATES TELOMERASE ACTIVITY IN HL-60 CELLS

    Institute of Scientific and Technical Information of China (English)

    何冬梅; 张洹

    2002-01-01

    Objective: To evaluate whether arsenic trioxide (AS2O3) could downregulate human telomerase reverse transcriptase (hTERT) gene expression and telomerase activity during induction of apoptosis of HL-60 cells. Methods: Apoptosis was detected by morphological observation and flow cytomertric cell cycle analysis. The expression of hTERT at mRNA and protein levels was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence using fluoresce isothiocyanate (FITC) label, respectively. Telomerase activity was determined by polymerase chain reaction enzyme-linked immunoassay (PCR-ELISA). Results: Treatment of 2 μmol/L at As2O3 could induce apoptosis of HL-60 cells. hTERT was decreased at both mRNA and protein levels during apoptosis of HL-60 cells. Telomerase activity of HL-60 cells was significantly inhibited. Conclusion:It is suggested that telomerase activity of HL-60 cells might be specifically inhibited by AS2O3 through the downregulation of hTERT gene expression.

  4. Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwei Wang

    2012-08-01

    Full Text Available Arsenic trioxide has been reported to inhibit cell growth and induce apoptotic cell death in many human cancer cells including breast cancer. However, the precise molecular mechanisms underlying the anti-tumor activity of arsenic trioxide are still largely unknown. In the present study, we assessed the effects of arsenic trioxide on cell viability and apoptosis in breast cancer cells. For mechanistic studies, we used multiple cellular and molecular approaches such as MTT assay, apoptosis ELISA assay, gene transfection, RT-PCR, Western blotting, and invasion assays. For the first time, we found a significant reduction in cell viability in arsenic trioxide-treated cells in a dose-dependent manner, which was consistent with induction of apoptosis and also associated with down-regulation of Notch-1 and its target genes. Taken together, our findings provide evidence showing that the down-regulation of Notch-1 by arsenic trioxide could be an effective approach, to cause down-regulation of Bcl-2, and NF-κB, resulting in the inhibition of cell growth and invasion as well as induction of apoptosis. These results suggest that the anti-tumor activity of arsenic trioxide is in part mediated through a novel mechanism involving inactivation of Notch-1 and its target genes. We also suggest that arsenic trioxide could be further developed as a potential therapeutic agent for the treatment of breast cancer.

  5. Arsenic trioxide plus PX-478 achieves effective treatment in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Lang, Mingxiao; Wang, Xiuchao; Wang, Hongwei; Dong, Jie; Lan, Chungen; Hao, Jihui; Huang, Chongbiao; Li, Xin; Yu, Ming; Yang, Yanhui; Yang, Shengyu; Ren, He

    2016-08-10

    Arsenic trioxide (ATO) has been selected as a promising treatment not only in leukemia but also in solid tumors. Previous studies showed that the cytotoxicity of ATO mainly depends on the induction of reactive oxygen species. However, ATO has only achieved a modest effect in pancreatic ductal adenocarcinoma, suggesting that the existing radical scavenging proteins, such as hypoxia inducible factor-1, attenuate the effect. The goal of this study is to investigate the effect of combination treatment of ATO plus PX-478 (hypoxia-inducible factor-1 inhibitor) and its underlying mechanism. Here, we showed that PX-478 robustly strengthened the anti-growth and pro-apoptosis effect of ATO on Panc-1 and BxPC-3 pancreatic cancer cells in vitro. Meanwhile, in vivo mouse xenograft models also showed the synergistic effect of ATO plus PX-478 compared with any single agent. Further studies showed that the anti-tumor effect of ATO plus PX-478 was derived from the reactive oxygen species-induced apoptosis. We next confirmed that Hypoxia-inducible factor-1 cleared reactive oxygen species by its downstream target, forkhead box O transcription factors, and this effect may justify the strategy of ATO plus PX-478 in the treatment of pancreatic cancer. PMID:27212442

  6. Evidences of Protective Potentials of Microdoses of Ultra-High Diluted Arsenic Trioxide in Mice Receiving Repeated Injections of Arsenic Trioxide

    Directory of Open Access Journals (Sweden)

    Pathikrit Banerjee

    2011-01-01

    Full Text Available The present study was undertaken to examine if microdoses of ultra-high diluted arsenic trioxide (a potentized homeopathic remedy, Arsenicum Album 200C, diluted 10-400 times have hepatoprotective potentials in mice subjected to repeated injections of arsenic trioxide. Arsenic intoxicated mice were divided into: (i those receiving Arsenicum Album-200C daily, (ii those receiving the same dose of diluted succussed alcohol (Alc 200C and (iii another group receiving neither drug nor succussed alcohol. Two other control groups were also maintained: one fed normal diet only and the other receiving normal diet and Alc-200C. Toxicity biomarkers like aspartate and alanine aminotransferases, glutathione reductase, catalase, succinate dehydrogenase, superoxide dismutase and reduced glutathione contents were periodically assayed keeping the observer “blinded”. Additionally, electron microscopic studies and gelatin zymography for matrix metalloproteinases of liver tissues were made at day 90 and 120. Blood glucose, hemoglobin, estradiol and testosterone contents were also studied. Compared to controls, Arsenicum Album-200C fed mice showed positive modulations of all parameters studied, thereby providing evidence of protective potentials of the homeopathic drug against chronic arsenic poisoning.

  7. Effect of TAK1 gene silencing on the apoptosis of Kasumi-1 cells induced by arsenic trioxide

    Institute of Scientific and Technical Information of China (English)

    许锦霞

    2013-01-01

    Objective To study the effect of transforming growth factor-βactivated kinase-1 (TAK1) gene silencing on the proliferation and apoptosis of Kasumi-1 cells induced by arsenic trioxide (As2O3) .Methods Acute myeloid

  8. EFFECT OF ARSENIC TRIOXIDE OR ATRA ON PRIMARY APL CELL OR HL-60 CELLS AND THEIR VALUE ANALYSIS IN HYPERLEUKOCYTOSIS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To detect the effect of arsenic trioxide or ATRA on APL cells or HL-60 cells and to investigate the mechanism of the hyperleukocytosis and detect the cross resistance between ATRA and arsenic trioxide. Methods: The number of promyelocytes or more matured granulocytes were counted by regular method, MTT test was used to measure the proliferation of HL-60 cells or APL cells, flow cytometry analysis to measure the apoptosis, NBT method to detect the differentiation of HL-60 cells or APL cells. Results: The proliferation of primary APL cells or HL-60 cells could be inhibited in vitro by either arsenic trioxide or ATRA, which could induce obvious apoptosis or obvious differentiation of primary APL cells or HL-60 cells. Inhibition of proliferation or apoptosis of ATRA resistant HL-60 cells were achieved by exposure toarsenic trioxide in vitro. On the other hand, the results of in vivo treatment showed that arsenic trioxide also induce of hyperleukocytosis. Conclusion: The results indicated that the hyperleukocytosis induced by ATRA is not contributed to the mechanism of more differentiation than apoptosis, there was not cross resistance between ATRA and arsenic trioxide.

  9. Role of Calcium Ion in Apoptosis of MD Cancer Cells Induced by Arsenic Trioxide

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jiuli; WANG Jintao; XU Shiwen

    2008-01-01

    In order to observe the role of calcium ion in apoptosis of MD cancer cells induced by arsenic trioxide, inhibition percentage was detected by MTT assay;morphology changes were examined by fluorescence microscope;apoptosis was examined by DNA Ladder;[Ca2+]i was investigated by spectrofluorimeter in vitro on MDCC-MSB1 cells. The results showed that As2O3 inhibited the proliferation of MDCC-MSB1 cells in concentration dependent manner (P<0.05 or P<0.01);typical apoptosis character was observed by fluorescence microscope;DNA Ladder was observed;the [Ca2+]i was elevated significantly after the treatment of As203 (P<0.05 or P<0.01) and showed a dose-dependent manner. It is concluded that the calcium may play an important role in apoptosis of MD cancer cells induced by arsenic trioxide.

  10. Effects of arsenic trioxide on the methylation of TMS1 gene in K562 cells

    Institute of Scientific and Technical Information of China (English)

    李洪丽

    2014-01-01

    Objective To detect the methylation status of TMS1gene and its demethylation by arsenic trioxide(As2O2)in K562 cells.Methods K562 cells were treated with different concentrations of As2O2for 48 hours.Methylationspecific PCR(MSP)was used to determine the methylation status of TMS1.RT-PCR and Western blot were used to detect the levels of TMS1 mRNA and protein.

  11. Arsenic Trioxide Induces Apoptosis in Human Platelets via C-Jun NH2-Terminal Kinase Activation

    OpenAIRE

    Yicun Wu; Jin Dai; Weilin Zhang; Rong Yan; Yiwen Zhang; Changgeng Ruan; Kesheng Dai

    2014-01-01

    Arsenic trioxide (ATO), one of the oldest drugs in both Western and traditional Chinese medicine, has become an effective anticancer drug, especially in the treatment of acute promyelocytic leukemia (APL). However, thrombocytopenia occurred in most of ATO-treated patients with APL or other malignant diseases, and the pathogenesis remains unclear. Here we show that ATO dose-dependently induces depolarization of mitochondrial inner transmembrane potential (ΔΨm), up-regulation of Bax and down-re...

  12. Therapeutic Potential of Delivering Arsenic Trioxide into HPV-Infected Cervical Cancer Cells Using Liposomal Nanotechnology

    OpenAIRE

    Wang, Xiaoyan; Li, Dong; Ghali, Lucy; Xia, Ruidong; Munoz, Leonardo P.; Garelick, Hemda; Bell, Celia M.; Wen, Xuesong

    2016-01-01

    Arsenic trioxide (ATO) has been used successfully to treat acute promyelocytic leukaemia, and since this discovery, it has also been researched as a possible treatment for other haematological and solid cancers. Even though many positive results have been found in the laboratory, wider clinical use of ATO has been compromised by its toxicity at higher concentrations. The aim of this study was to explore an improved method for delivering ATO using liposomal nanotechnology to evaluate whether t...

  13. Gene Expression Profile of Multiple Myeloma Cell Line Treated by Arsenic Trioxide

    Institute of Scientific and Technical Information of China (English)

    WANG Mengchang; LIU Shaanxi; LIU Pengbo

    2007-01-01

    cDNA microarray was used to compare the gone expression profiles of multiple myeloma cell line RPMI8226 24 h before and after treatment with arsenic trioxide. Two eDNA probes were prepared by mRNA reverse transcription of both arsenic trioxide-treated and untreated RPMI8226 cells. The probes were labeled with Cy3 and Cy5 fluorescence dyes separately, hybridized with cDNA microarray representing 4096 different human genes, and scanned for fluorescence intensity. The differences in gene expression were calculated on the basis of the ratios of signal intensity of treated and untreated samples. The up- and down-regulated genes were screened through the analysis of gene expression ratios. The results showed that 273 genes were differentially altered at mRNA level, 121 genes were up-regulated and 152 were down-regulated. It is concluded that the treatment with arsenic trioxide can induce a variety of gene changes in RPMI8226 cell line. Many genes may be involved in the pathogenesis of multiple myeloma. ALK-1 and TXNIP genes may play an impor- tant role in the apoptosis and partial differentiation of RPMI8226 cells.

  14. Swallowing a bitter pill-oral arsenic trioxide for acute promyelocytic leukemia.

    Science.gov (United States)

    Torka, Pallawi; Al Ustwani, Omar; Wetzler, Meir; Wang, Eunice S; Griffiths, Elizabeth A

    2016-05-01

    Parenteral arsenic trioxide (ATO) has been firmly established as a standard therapy for acute promyelocytic leukemia (APL). Despite widespread use of oral arsenicals in medicine historically, they had disappeared from modern pharmacopeia until oral ATO was redeveloped in Hong Kong in 2000. Since then, over 200 patients with leukemia (predominantly APL) have been treated with oral ATO in Hong Kong and China. Oral arsenic trioxide and other formulations of arsenic appear to have a clinical efficacy comparable to that of IV formulations. These drugs given orally also appear to have a slightly better safety profile, lower operational costs and improved convenience for patients. The clinical experience with oral ATO has previously been reported piecemeal as case series, pilot studies or subgroup analyses rather than in a comprehensive cohort. In this report we attempt to synthesize the published English language literature on oral arsenicals and present the argument for further development of these compounds. Systematic study of this drug with well-designed randomized multi-center clinical trials is needed to accelerate its development and incorporation into clinical practice. PMID:26709030

  15. Therapeutic efficacy of new dimercaptosuccinic acid (DMSA) analogues in acute arsenic trioxide poisoning in mice.

    Science.gov (United States)

    Kreppel, H; Paepcke, U; Thiermann, H; Szinicz, L; Reichl, F X; Singh, P K; Jones, M M

    1993-01-01

    The therapeutic efficacy of six newly synthesized analogues of dimercaptosuccinic acid (DMSA) was investigated in acute arsenic trioxide poisoning in mice. Meso-2,3-di(acetylthio)succinic acid (DATSA) and meso-2,3- di(benzoylthio)succinic acid (DBTSA) are analogues of DMSA with protected thiol groups ("prodrugs"), and DMDMS, DEDMS, DnPDMS, and DiPDMS are various di-esters of DMSA with methyl, ethyl, n-propyl, and isopropyl alcohols, respectively. Thirty minutes after s.c. injection of an LD80 of arsenic trioxide (65 mumol/kg) male NMRI mice were treated with a single equimolar dose (0.7 mmol/kg) of DMSA i.p. or one of the analogues i.p. or via gastric tube (i.g.). Control animals received arsenic trioxide and saline 30 min later. The survival rate was recorded for 30 days. All of the animals treated with DMSA i.p. survived and all controls died within 2 days. Administered i.g., DATSA and DBTSA increased the survival rate to 29% and 43%, and injected i.p. to 86%. Treatment with DMDMS i.p. and i.g., and with DEDMS, DnPDMS, and DiPDMS i.g. did not reduce lethality. Given i.p., DnPDMS increased the survival rate to 72%, and DEDMS and DiPDMS to 86%, respectively. To investigate the efficacy of the DMSA analogues in reducing the tissue content of arsenic, male NMRI mice received an s.c. injection of an LD5 of arsenic trioxide containing a tracer dose of 73-As(III) (42.5 mumol/kg body wt). Thirty minutes later, saline (controls) or a single equimolar dose (0.7 mmol/kg) of DMSA i.p., or one of the analogues i.p. or i.g. was administered. The arsenic content of various organs (blood, liver, kidneys, heart, lungs, spleen, small intestine, large intestine, brain, testes, skeletal muscle, and skin) at 30 min, 2 h, 4 h, 6 h, and 8 h after the arsenic injection was measured using a gamma counter.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Preparation of Arsenic Trioxide Albumin Microspheres and its Release Characteristics in Vitro

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jie; ZENG Fuqing; GAO Xiang; XIE Shusheng; WEI Shuli

    2005-01-01

    Summary: Arsenic trioxide albumin microspheres (As2O3-BSA-NS) were prepared by using methods of chemical cross-linking. The desirability function (DF), calculated according to the size (0.05). The release experiment in vitro showed that As2O3 in As2O3-BSA-NS was released more slower than pure As2O3. It was concluded that regular As2O3-BSA-NS may be prepared by the methods of chemical cross-linking, which was optimized by orthogonal experimental analysis of different factors, and the microspheres can release As2O3 slowly.

  17. Mitigation of hepatotoxic effects of arsenic trioxide through omega-3 fatty acid in rats.

    Science.gov (United States)

    Mathews, Varghese V; Paul, Mv Sauganth; Abhilash, M; Manju, Alex; Abhilash, S; Nair, R Harikumaran

    2014-10-01

    Arsenic trioxide (As(2)O(3)) is an effective drug in the treatment of leukaemia and many solid tumours. In clinical trials, arsenic therapy is closely associated with hepatic toxicity. The present study was designed to investigate the efficacy of omega-3 fatty acid against As(2)O(3)-induced hepatotoxicity. A 4 mg/kg body weight (bw) of As(2)O(3) was orally administered to Wistar male rats for 45 days. Hepatotoxicity was evaluated by biochemical tests, antioxidant assays and histopathological examinations. Arsenic accumulation was found in the liver tissue of rats treated with As(2)O(3). Hepatoprotective efficacy of omega-3 fatty acid was analysed by the combination therapy with As(2)O(3). In vivo studies revealed a significant rise in lipid peroxidation with concomitant decline in reduced glutathione, glutathione-dependant antioxidant enzymes and antiperoxidative enzymes in the liver tissue of rats treated with arsenic. The supplementation of omega-3 fatty acid at a dose of 50 mg/kg bw with As(2)O(3) offers ameliorative effect against hepatocellular toxicity. Omega-3 fatty acid maintained hepatic marker enzymes, antioxidant enzymes and decreased lipid peroxidation. The combination treatment clearly reduced the hepatic structural abnormalities such as haemorrhage, necrosis and cholangiofibrosis in the rats treated with arsenic. This study concludes that the omega-3 fatty acid might be useful for the protection against As(2)O(3)-induced hepatotoxicity.

  18. Inhibitory Effect of Arsenic Trioxide on Growth and Telomerase Activity of SMMC-7721 and BEL-7402 Hepatocarcinoma Cells and Determination of their GSH Content

    Institute of Scientific and Technical Information of China (English)

    Weiwei Ren; Hong Li; Yuan Zhang

    2006-01-01

    OBJECTIVE To explore the inhibitory effect of arsenic trioxide on growth and telomerase activity of BEL-7402 and SMMC-7721 hepatocarcinoma cells, and to measure their GSH level.METHODS Cell culture and trypan blue exclusion were used to examine the inhibitory effect of arsenic trioxide on BEL-7402 and SMMC-7721 hepatocarcinoma lines. A GSH kit and telomerase kit were used to mearsure the GSH content in cells and telomerase activity.RESULTS The growth of BEL-7402 cells was significantly inhibited at a level of 0.50 μmol/L of arsenic trioxide by 24 h. The inhibitory effect increased with time and concetration of arsenic trioxide. The telomerase activity of BEL-7402 cells was also significantly inhibited at a level of 0.50 μmol/L of arsenic trioxide by 24 h, after which the inhibitory effect increased with time. On the other hand, at 24 h of incubation a level of 2.00 μmol/L of arsenic trioxide was required to significantly inhibit growth of SMMC-7721 cells, and only after 48 h with 2.00 μmol/L of arsenic trioxide did telomerase activity significantly decline. The GSH content of the BEL-7402 and SMMC-7721 cells was 18.7±1.4 and 50.8±5.2 nmol/mg protein respectively, a significant difference.CONCLUSION Different concentrations of arsenic trioxide are required to inhibit growth and telomerase activity of SMMC-7721 and BEL-7402cells. Perhaps BEL-7402 cells are more sensitive to arsenic trioxide because of their low level of GSH content, which results in a low capacity for oxidation-reduction and poorer detoxification mechanisms in BEL-7402 cells.

  19. Evaluation of chronic toxicity of Kushta Sammulfar (calx of Arsenic trioxide

    Directory of Open Access Journals (Sweden)

    Athar Parvez Ansari

    2013-06-01

    Full Text Available Sammulfar (arsenic trioxide is a notorious poison and has extensively been studied for its toxicity. It is in use for various purposes for centuries and is used even today as a therapeutic agent in the form of kushta (calx in traditional systems of medicine, particularly Unani medicine, but without apparent safety data. The present study, therefore, was conducted to produce data for prolong use of calx of arsenic trioxide. The calx (test drug was prepared by the method described in National Formulary of Unani Medicine. The study was carried in healthy Wistar rats of either sex; weighing 150-250 g; 2-3 months of age, in a dose dependent manner, following the methods of Gupta et al. (2002, Ghosh (2008 and Klaassan (2008. The animals were divided into four groups of 10 animals each. Group I served as control, where as group II, III and IV were used for three dose levels of the test drug i.e. low (8.75 mg–1 kg, medium (17.50 mg–1 kg and higher (26.25 mg–1 kg. Standard parameters usually applied for chronic toxicity studies were considered. The study revealed dose dependent toxicity. Usual signs of chronic toxicity were observed during the study. Low dose of Kushta Sammulfar (KSF did not produce remarkable toxic effects. Mild to moderate toxicity was seen in KSF-II and KSF-III.

  20. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Robbins, David J. [Department of Surgery, Molecular Oncology Program, Miller School of Medicine, University of Miami, Miami (United States); Matalon, Sadis [Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S. [Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Afaq, Farrukh [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Bickers, David R. [Department of Dermatology, Columbia University Medical Center, New York (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

    2013-11-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.

  1. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    International Nuclear Information System (INIS)

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions

  2. Inflammatory Factor Alterations in the Gastrointestinal Tract of Cocks Overexposed to Arsenic Trioxide.

    Science.gov (United States)

    Xing, Mingwei; Zhao, Panpan; Guo, Guangyang; Guo, Ying; Zhang, Kexin; Tian, Li; He, Ying; Chai, Hongliang; Zhang, Wen

    2015-10-01

    Exposure of people and animals to arsenic (As) is a global public health concern because As is widely distributed and associated with numerous adverse effects. As is a poisonous metalloid and arsenic trioxide (As2O3) is a form of As. Thus far, there have been very few reports on the inflammatory factor alterations of the gastrointestinal tract in birds exposed to As2O3. To investigate the possible correlation of As2O3 with inflammatory injury induced by an arsenic-supplemented diet in birds, 72 1-day-old male Hy-line cocks were selected and randomly divided into four groups. They were fed with either a commercial diet or an arsenic-supplemented diet containing 7.5, 15, and 30 mg/kg As2O3. The experiment lasted for 90 days, and samples of gizzard, glandular stomach, duodenum, jejunum, ileum, cecum, and rectum were collected at days 30, 60, and 90 of the experiment period. The inflammation-related genes were determined, including NF-κB, iNOS, COX-2, PTGEs, and TNF-α. The connection between arsenic dosage and inflammation-related genes was assessed. The content of inducible NO synthase (iNOS) was measured by Western blot of the samples. The results showed that arsenic supplementation increased the mRNA expression levels of inflammation-related genes in the gastrointestinal tract of cocks at different time points (p function regression of the gastrointestinal tract by affecting inflammation-related genes and iNOS in cocks. This study offers some information on the mechanism of gastrointestinal tract inflammatory injury and iNOS expression level alterations induced by arseniasis. PMID:25784090

  3. The effect of arsenic trioxide on QT interval prolongation during APL therapy

    Institute of Scientific and Technical Information of China (English)

    周晋; 孟然; 李晓霞; 吕成芳; 范圣瑾; 杨宝峰

    2003-01-01

    Objective To investigate the cardiac effect of QT interval prolongation in the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (As2O3), and the relationship between QT and serum arsenic concentration.Methods Blood serum arsenic concentrations of thirty APL patients were determined at 2 hours, 4 hours, 8 hours, and 24 hours after As2O3 injection using atomic fluorophotometry. Cardiac functions were measured simultaneously using a 12-lead body-surface electrocardiogram (ECG). Q-T intervals were manually measured, and then corrected using Bazett ' s formula (QTc). QT dispersion (QTd) was also calculated. In order to assess the effects of arsenic on the symptoms of anemia, twenty-four anemia patients were divided into two groups on the basis hemoglobin concentration: Group1 (Hb≥90 g/L), and Group 2 (60 g/L≤Hb<90 g/L). QTc and QTd of these patients were also manually measured.Results All QT intervals of APL patients treated with As2O3 injection were prolonged [32.2 ms (27, 41 ms); P 0.05]. There was a delay of 2 hours in maximum QTc following peaks in serum arsenic concentration. Changes in QTc and QTd of the two anemic groups were not prominent.Conclusions As2O3 can prolong QTc intervals in APL patients, but the effects are delayed compared to peak serum arsenic concentrations. As2O3 has no prolongation effect on QTd. Mild and moderate anemia do not effect QTc and QTd.

  4. Enhanced suppression of tumor growth by concomitant treatment of human lung cancer cells with suberoylanilide hydroxamic acid and arsenic trioxide

    Energy Technology Data Exchange (ETDEWEB)

    Chien, Chia-Wen [Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (China); Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan (China); Yao, Ju-Hsien [Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan (China); Chang, Shih-Yu [Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (China); Lee, Pei-Chih [Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan (China); Lee, Te-Chang, E-mail: bmtcl@ibms.sinica.edu.tw [Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan (China)

    2011-11-15

    The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL) and relapsed APL has been well documented. ATO may cause DNA damage by generating reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, modulates gene and protein expression via histone-dependent or -independent pathways that may result in chromatin decondensation, cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO and SAHA act synergistically to enhance the death of cancer cells. Our current findings showed that combined treatment with ATO and SAHA resulted in enhanced suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivo in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed that apoptotic cell death was significantly enhanced after combined treatment with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells; however, co-treatment with SAHA significantly increased ATO-induced DNA damage. Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation and increase cellular susceptibility to ATO-induced DNA damage. Combined administration of SAHA and ATO may be an effective approach to the treatment of lung cancer. -- Highlights: Black-Right-Pointing-Pointer ATO and SAHA are therapeutic agents with different action modes. Black-Right-Pointing-Pointer Combination of ATO and SAHA synergistically inhibits tumor cell growth. Black-Right-Pointing-Pointer SAHA loosens chromatin structure resulting in increased sensitivity to DNase I. Black-Right-Pointing-Pointer ATO-induced DNA damage and apoptosis are enhanced by co-treatment with SAHA.

  5. 三氧化二砷与癌细胞凋亡%Arsenic Trioxide and Carcinoma Cell Apoptosis

    Institute of Scientific and Technical Information of China (English)

    王建华; 徐小英; 王远亮

    2002-01-01

      Arsenic trioxide, an inorganic compound of trivalent arsenic, is highly poisonous after acute exposure and carcinogenic following chronic exposure. Although arsenicals have long been used therapeutically, they have aroused increasing interest recently by the discovery that arsenic trioxide can induce apoptosis in the APL cell and other cancer cells. The article demonstrates the relative concepts of apoptosis and summarizes the effect of arsenic trioxide to the carcinoma, its possible principle included.%  三氧化二砷是一种剧毒化合物,长期接触会致癌。作为药物,砷化合物已有很久历史,近期由于其可诱导急性早幼粒白血病细胞和其它癌细胞凋亡而备受关注。文章叙述了细胞凋亡的相关概念,总结了三氧化二砷近年来对癌细胞的凋亡作用以及其可能的机理。

  6. Sulindac enhances arsenic trioxide induced apoptotic potential mediated by reactive oxygen species production in arsenic trioxide-resistant A549 lung carcinoma cells

    International Nuclear Information System (INIS)

    Full text: Recent reports indicate a broad spectrum of antitumor activity for arsenic trioxide (As2 O3) due to its ability to induce apoptosis via intracellular production of reactive oxygen species (ROS). Sulindac and nonsteroidal anti-inflammatory drugs induce apoptosis in a variety of cancer cells, including those of colon, prostate, breast, and leukemia. Therefore, we examined the effects of sulindac on As2O3-induced apoptosis in As2 O3-resistant A549 lung carcinoma cells in clinically available concentrations. Sulindac produced hydrogen peroxide (H 2 O 2 ) and nitric oxide (NO) in a dose-dependent manner and greatly sensitized the cells to As2O3-induced apoptosis. Apoptotic cell death was preceded by collapse of the mitochondrial membrane potential, release of cytochrome c/apoptosis inducing factor(AIF) and activation of caspase-3, -8, -9 activation. Importantly, the combined effect of As2O3 and sulindac was associated with an increased production of intracellular H2O3/reactive nitrogen species(RNS) and was completely suppressed by the reduced glutathione. In conclusion, intracellular ROS/RNS products most likely constitute the key mediators contributing to the combined effect of As2O3 and sulindac. Our data provide evidence for the first time that sulindac may help to extend the therapeutic spectrum of As2O3 and suggest that the combination of As2O3 and sulindac could be more broadly applied in cancer therapy

  7. Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met oncogene addiction in cancer cells

    Science.gov (United States)

    Kryeziu, Kushtrim; Pirker, Christine; Englinger, Bernhard; van Schoonhoven, Sushilla; Spitzwieser, Melanie; Mohr, Thomas; Körner, Wilfried; Weinmüllner, Regina; Tav, Koray; Grillari, Johannes; Cichna-Markl, Margit; Berger, Walter; Heffeter, Petra

    2016-01-01

    As an environmental poison, arsenic is responsible for many cancer deaths. Paradoxically, arsenic trioxide (ATO) presents also a powerful therapy used to treat refractory acute promyelocytic leukemia (APL) and is intensively investigated for treatment of other cancer types. Noteworthy, cancer therapy is frequently hampered by drug resistance, which is also often associated with enhancement of tumor aggressiveness. In this study, we analyzed ATO-selected cancer cells (A2780ATO) for the mechanisms underlying their enhanced tumorigenicity and aggressiveness. These cells were characterized by enhanced proliferation and spheroid growth as well as increased tumorigenicity of xenografts in SCID mice. Noteworthy, subsequent studies revealed that overexpression of Met receptor was the underlying oncogenic driver of these effects, as A2780ATO cells were characterized by collateral sensitivity against Met inhibitors. This finding was also confirmed by array comparative genomic hybridization (array CGH) and whole genome gene expression arrays, which revealed that Met overexpression by chronic ATO exposure was based on the transcriptional regulation via activation of AP-1. Finally, it was shown that treatment with the Met inhibitor crizotinib was also effective against A2780ATO cell xenografts in vivo, indicating that targeting of Met presents a promising strategy for the treatment of Met-overexpressing tumors after either arsenic exposure or failure to ATO treatment. PMID:27036042

  8. Inhibition of interleukin-13 gene expression in T cells through GATA-3 pathway by arsenic trioxide

    Institute of Scientific and Technical Information of China (English)

    YAO Xin; HE Hai-yan; YANG Yan; DAI Shan-lin; SUN Pei-li; YIN Kai-sheng; HUANG Mao

    2008-01-01

    @@ Arsenic trioxide (AT) has a long history of use in both traditional Chinese medicine and in modern medicine in asthma therapy.Recently,Yin et al1 found that AT even at small doses reduced the airway inflammation of sensitized guinea pigs.However the mechanism underlying this is still largely unknown.Interleukin 13 (IL-13),as one of the important TH2 cytokines,plays an important role in asthma pathogenesis through promoting eosinophilic inflammation,mucus secretion and airway hyperresponsiveness.2 To further explore the molecular anti-inflammatory basis of AT,we employed Hut-78 cells,a human T cell line,with activation via CD3/CD28 receptors to mimick in vivo co-stimulation to investigate the effect of AT on IL-13 transcription.

  9. Experimental study on antitumor effect of arsenic trioxide in combination with cisplatin ordoxorubicin on hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Shu-Kui Qin; Bao-An Chen; Hui-Ying Chen

    2001-01-01

    @@ INTRODUCTION The main component of a traditional Chinese drug "Pishuang". arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.

  10. Erythema multiforme due to arsenic trioxide in a case of acute promyelocytic leukemia: A diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Girish V Badarkhe

    2016-01-01

    Full Text Available Erythema multiforme (EM is an acute, self-limited, Type IV hypersensitivity reactions associated with infections and drugs. In this case of acute promyelocytic leukemia, EM diagnosed during the induction phase was mistakenly attributed to vancomycin used to treat febrile neutropenia during that period. However, the occurrence of the lesions of EM again during the consolidation phase with arsenic trioxide (ATO lead to a re-evaluation of the patient and both the Naranjo and World Health Organization-Uppsala Monitoring Centre scale showed the causality association as “probable.” The rash responded to topical corticosteroids and antihistamines. This rare event of EM being caused by ATO may be attributed to the genetic variation of methyl conjugation in the individual which had triggered the response, and the altered metabolic byproducts acted as a hapten in the subsequent keratinocyte necrosis.

  11. Erythema multiforme due to arsenic trioxide in a case of acute promyelocytic leukemia: A diagnostic challenge.

    Science.gov (United States)

    Badarkhe, Girish V; Sil, Amrita; Bhattacharya, Sabari; Nath, Uttam Kumar; Das, Nilay Kanti

    2016-01-01

    Erythema multiforme (EM) is an acute, self-limited, Type IV hypersensitivity reactions associated with infections and drugs. In this case of acute promyelocytic leukemia, EM diagnosed during the induction phase was mistakenly attributed to vancomycin used to treat febrile neutropenia during that period. However, the occurrence of the lesions of EM again during the consolidation phase with arsenic trioxide (ATO) lead to a re-evaluation of the patient and both the Naranjo and World Health Organization-Uppsala Monitoring Centre scale showed the causality association as "probable." The rash responded to topical corticosteroids and antihistamines. This rare event of EM being caused by ATO may be attributed to the genetic variation of methyl conjugation in the individual which had triggered the response, and the altered metabolic byproducts acted as a hapten in the subsequent keratinocyte necrosis. PMID:27114640

  12. STUDY ON THE RELATIONSHIP OF ARSENIC TRIOXIDE-INDUCED BIOLOGICAL EFFECTS AND DEGRADATIONOF PML PROTEINS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To understand whether arsenic trioxide (As2O3)-induced biological effects are associated with degradation of PML proteins. Methods Acute promyelocytic leukemia (APL) cell line NB4, acute T-lymphocytic leukemia cell line Jurkat, acute myeloid leukemia cell line U937, and chronic myelocytic leukemia blast crisis cell line K562 were used as in vitro models. In different cell lines, the As2O3-induced bio- logical effects were determined by cell growth, cell viability, cell morphology, and flow cytometry assay on sub- G1 cell content. The alteration of PML proteins was analyzed by immunofluorescence. Results In terms of growth inhibition and apoptosis induction, 1.0μmol/L As2O3 had different effects on different cell lines. However, degradation of PML proteins occurred in all the cell lines with As2O3 treatment. Conclusion As2O3-induced biological effects may be independent of PML protein degradation.

  13. Arsenic trioxide: impact on the growth and differentiation of cancer cells and possible use in cancer therapy

    Directory of Open Access Journals (Sweden)

    Ewelina Hoffman

    2013-08-01

    Full Text Available Arsenic trioxide (As2O3 has recently been identified as an effective drug in different types of cancer therapy. It is a useful pharmacological agent in acute promyelocytic leukemia (APL treatment, especially the form that is resistant to conventional chemotherapy with all-trans retinoic acid (ATRA. What is more, laboratory data suggest that As2O3 is also active when it comes to several solid tumor cell lines. However, the mechanism of action is not fully understood. As2O3 in high doses triggers apoptosis, while in lower concentrations it induces partial differentiation. The As2O3 mechanism of action involves effects on mitochondrial transmembrane potential which lead to apoptosis. It also acts on the activity of JNK kinase, glutathione, caspases, NF-ĸB nuclear factor or pro- and antiapoptotic proteins. This publication presents the current knowledge about the influence of arsenic trioxide in cancer cells.

  14. Comparison of Newly Diagnosed and Relapsed Patients with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide: Insight into Mechanisms of Resistance

    OpenAIRE

    Ezhilarasi Chendamarai; Saravanan Ganesan; Ansu Abu Alex; Vandana Kamath; Nair, Sukesh C.; Arun Jose Nellickal; Nancy Beryl Janet; Vivi Srivastava; Kavitha M Lakshmi; Auro Viswabandya; Aby Abraham; Mohammed Aiyaz; Nandita Mullapudi; Raja Mugasimangalam; Rose Ann Padua

    2015-01-01

    There is limited data on the clinical, cellular and molecular changes in relapsed acute promyeloytic leukemia (RAPL) in comparison with newly diagnosed cases (NAPL). We undertook a prospective study to compare NAPL and RAPL patients treated with arsenic trioxide (ATO) based regimens. 98 NAPL and 28 RAPL were enrolled in this study. RAPL patients had a significantly lower WBC count and higher platelet count at diagnosis. IC bleeds was significantly lower in RAPL cases (P=0.022). The ability of...

  15. Arsenic trioxide induces oxidative stress, DNA damage, and mitochondrial pathway of apoptosis in human leukemia (HL-60) cells

    OpenAIRE

    Kumar, Sanjay; Yedjou, Clement G.; Tchounwou, Paul B.

    2014-01-01

    Background Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), which accounts for approximately 10% of all acute myloid leukemia cases. It is a blood cancer that is formed by chromosomal mutation. Each year in the United States, APL affects about 1,500 patients of all age groups and causes approximately 1.2% of cancer deaths. Arsenic trioxide (ATO) has been used successfully for treatment of APL patients, and both induction and consolidated therapy have resulted i...

  16. The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel

    Directory of Open Access Journals (Sweden)

    Liu Qian

    2010-08-01

    Full Text Available Abstract Background Drinking water contaminated with inorganic arsenic is associated with increased risk for different types of cancer. Paradoxically, arsenic trioxide can also be used to induce remission in patients with acute promyelocytic leukemia (APL with a success rate of approximately 80%. A comprehensive study examining the mechanisms and potential signaling pathways contributing to the anti-tumor properties of arsenic trioxide has not been carried out. Methods Here we applied a systems biology approach to identify gene biomarkers that underlie tumor cell responses to arsenic-induced cytotoxicity. The baseline gene expression levels of 14,500 well characterized human genes were associated with the GI50 data of the NCI-60 tumor cell line panel from the developmental therapeutics program (DTP database. Selected biomarkers were tested in vitro for the ability to influence tumor susceptibility to arsenic trioxide. Results A significant association was found between the baseline expression levels of 209 human genes and the sensitivity of the tumor cell line panel upon exposure to arsenic trioxide. These genes were overlayed onto protein-protein network maps to identify transcriptional networks that modulate tumor cell responses to arsenic trioxide. The analysis revealed a significant enrichment for the oxidative stress response pathway mediated by nuclear factor erythroid 2-related factor 2 (NRF2 with high expression in arsenic resistant tumor cell lines. The role of the NRF2 pathway in protecting cells against arsenic-induced cell killing was validated in tumor cells using shRNA-mediated knock-down. Conclusions In this study, we show that the expression level of genes in the NRF2 pathway serve as potential gene biomarkers of tumor cell responses to arsenic trioxide. Importantly, we demonstrate that tumor cells that are deficient for NRF2 display increased sensitivity to arsenic trioxide. The results of our study will be useful in

  17. Therapeutic Potential of Delivering Arsenic Trioxide into HPV-Infected Cervical Cancer Cells Using Liposomal Nanotechnology.

    Science.gov (United States)

    Wang, Xiaoyan; Li, Dong; Ghali, Lucy; Xia, Ruidong; Munoz, Leonardo P; Garelick, Hemda; Bell, Celia; Wen, Xuesong

    2016-12-01

    Arsenic trioxide (ATO) has been used successfully to treat acute promyelocytic leukaemia, and since this discovery, it has also been researched as a possible treatment for other haematological and solid cancers. Even though many positive results have been found in the laboratory, wider clinical use of ATO has been compromised by its toxicity at higher concentrations. The aim of this study was to explore an improved method for delivering ATO using liposomal nanotechnology to evaluate whether this could reduce drug toxicity and improve the efficacy of ATO in treating human papillomavirus (HPV)-associated cancers. HeLa, C33a, and human keratinocytes were exposed to 5 μm of ATO in both free and liposomal forms for 48 h. The stability of the prepared samples was tested using inductively coupled plasma optical emission spectrometer (ICP-OES) to measure the intracellular arsenic concentrations after treatment. Fluorescent double-immunocytochemical staining was carried out to evaluate the protein expression levels of HPV-E6 oncogene and caspase-3. Cell apoptosis was analysed by flow cytometry. Results showed that liposomal ATO was more effective than free ATO in reducing protein levels of HPV-E6 and inducing cell apoptosis in HeLa cells. Moreover, lower toxicity was observed when liposomal-delivered ATO was used. This could be explained by lower intracellular concentrations of arsenic. The slowly accumulated intracellular ATO through liposomal delivery might act as a reservoir which releases ATO gradually to maintain its anti-HPV effects. To conclude, liposome-delivered ATO could protect cells from the direct toxic effects induced by higher concentrations of intracellular ATO. Different pathways may be involved in this process, depending on local architecture of the tissues and HPV status. PMID:26887578

  18. Therapeutic Potential of Delivering Arsenic Trioxide into HPV-Infected Cervical Cancer Cells Using Liposomal Nanotechnology

    Science.gov (United States)

    Wang, Xiaoyan; Li, Dong; Ghali, Lucy; Xia, Ruidong; Munoz, Leonardo P.; Garelick, Hemda; Bell, Celia; Wen, Xuesong

    2016-02-01

    Arsenic trioxide (ATO) has been used successfully to treat acute promyelocytic leukaemia, and since this discovery, it has also been researched as a possible treatment for other haematological and solid cancers. Even though many positive results have been found in the laboratory, wider clinical use of ATO has been compromised by its toxicity at higher concentrations. The aim of this study was to explore an improved method for delivering ATO using liposomal nanotechnology to evaluate whether this could reduce drug toxicity and improve the efficacy of ATO in treating human papillomavirus (HPV)-associated cancers. HeLa, C33a, and human keratinocytes were exposed to 5 μm of ATO in both free and liposomal forms for 48 h. The stability of the prepared samples was tested using inductively coupled plasma optical emission spectrometer (ICP-OES) to measure the intracellular arsenic concentrations after treatment. Fluorescent double-immunocytochemical staining was carried out to evaluate the protein expression levels of HPV-E6 oncogene and caspase-3. Cell apoptosis was analysed by flow cytometry. Results showed that liposomal ATO was more effective than free ATO in reducing protein levels of HPV-E6 and inducing cell apoptosis in HeLa cells. Moreover, lower toxicity was observed when liposomal-delivered ATO was used. This could be explained by lower intracellular concentrations of arsenic. The slowly accumulated intracellular ATO through liposomal delivery might act as a reservoir which releases ATO gradually to maintain its anti-HPV effects. To conclude, liposome-delivered ATO could protect cells from the direct toxic effects induced by higher concentrations of intracellular ATO. Different pathways may be involved in this process, depending on local architecture of the tissues and HPV status.

  19. Granulocyte colony-stimulating factor potentiates differentiation induction by all-trans retinoic acid and arsenic trioxide and enhances arsenic uptake in the acute promyelocytic leukemia cell line HT93A.

    Science.gov (United States)

    Iriyama, Noriyoshi; Yuan, Bo; Hatta, Yoshihiro; Horikoshi, Akira; Yoshino, Yuta; Toyoda, Hiroo; Aizawa, Shin; Takeuchi, Jin

    2012-11-01

    The effects of arsenic trioxide (ATO), all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF), alone or in combination, were investigated by focusing on differentiation, growth inhibition and arsenic uptake in the acute promyelocytic leukemia (APL) cell line HT93A. ATO induced differentiation at low concentrations (0.125 µM) and apoptosis at high concentrations (1-2 µM). Furthermore, ATRA induced greater differentiation than ATO. No synergistic effect of ATRA and ATO was found on differentiation. G-CSF promoted differentiation-inducing activities of both ATO and ATRA. The combination of ATRA and G-CSF showed maximum differentiation and ATO addition was not beneficial. Addition of 1 µM ATRA and/or 50 ng/ml G-CSF to ATO did not affect apoptosis compared to ATO treatment alone. ATRA induced expression of aquaporin-9 (AQP9), a transmembrane transporter recognized as a major pathway of arsenic uptake, in a time- and dose-dependent manner. However, treatment with 1 µM ATRA decreased arsenic uptake by 43.7% compared to control subject. Although G-CSF addition did not enhance AQP9 expression in the cells, the reduced arsenic uptake was recovered to the same level as that in controls. ATRA decreased cell viability and addition of 50 ng/ml G-CSF to ATRA significantly increased the number of viable cells compared with that in ATRA alone treated cells. G-CSF not only promotes differentiation-inducing activities of both ATRA and ATO, but also makes APL cells vulnerable to increased arsenic uptake. These observations provide new insights into combination therapy using these three agents for the treatment of APL.

  20. Phytopathological and nutraceutical evaluation of cauliflower plants treated with high dilutions of arsenic trioxide

    Directory of Open Access Journals (Sweden)

    Lucietta Betti

    2012-09-01

    Full Text Available Introduction: This research aimed at verifying the effects of highly diluted (HD treatments on cauliflower (Brassica oleracea L. plants both healthy and inoculated by the fungus Alternaria brassicicola, causing the dark leaf spot disease. In vitro spore germination assays (A, growth chamber experiments (B and field trials (C were performed. Material and Methods: (A: spore suspensions were prepared in HD treatments and their inhibiting effect on germination was recorded microscopically after incubation at 25°C for 5 h. (B: the same treatments were tested in plants artificially inoculated with the fungus. The infection level on leaves was blindly evaluated by a previously defined infection scale. (C: the field was divided into plots according to a complete randomized block design. In the first trial (i, plants were artificially inoculated and weekly treated; the infection level was evaluated on cauliflower heads. The second trial (ii was performed on the same field with the aim to induce a natural infection, mediated by infected crop residues. Measurement endpoints concerned the evaluation of some physiological parameters along with the glucosinolate content on cauliflower heads. Results: (A: arsenic trioxide (As 35x and 35x diluted 1:5000 and Cuprum 5x induced highly significant inhibition of germination rate (-60% vs. control. (B: As 35x and Cu 3 g/l induced a significant decrease of mean infection level (-50%. (C: in (i, a significant reduction of disease symptoms on heads was recorded for As 35x and Cu 3 g/l (-45%. In (ii natural fungal infection did not occur due to dry weather conditions; physiological and nutraceutical analyses of healthy heads demonstrated that As 35x induced a significant increase of both head size and glucosinolate content. Discussion: Some evidences on the efficacy of arsenic, at different decimal and centesimal HD, in fungal and viral disease control were previously reported [1]. In the present study the

  1. Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma.

    Science.gov (United States)

    Boehme, Karen A; Zaborski, Julian J; Riester, Rosa; Schweiss, Sabrina K; Hopp, Ulrike; Traub, Frank; Kluba, Torsten; Handgretinger, Rupert; Schleicher, Sabine B

    2016-02-01

    Rhabdomyosarcomas (RMS) are soft tissue tumours treated with a combination of surgery and chemotherapy. However, mortality rates remain high in case of recurrences and metastatic disease due to drug resistance and failure to undergo apoptosis. Therefore, innovative approaches targeting specific signalling pathways are urgently needed. We analysed the impact of different hedgehog (Hh) pathway inhibitors on growth and survival of six RMS cell lines using MTS assay, colony formation assay, 3D spheroid cultures, flow cytometry and western blotting. Especially the glioma-associated oncogene family (GLI) inhibitor arsenic trioxide (ATO) effectively reduced viability as well as clonal growth and induced cell death in RMS cell lines of embryonal, alveolar and sclerosing, spindle cell subtype, whereas normal skeletal muscle cells were hardly compromised by ATO. Combination of ATO with itraconazole potentiated the reduction of colony formation and spheroid size. These results show that ATO is a promising substance for treatment of relapsed and refractory RMS by directly targeting GLI transcription factors. The combination with itraconazole or other chemotherapeutic drugs has the opportunity to enforce the treatment efficiency of resistant and recurrent RMS.

  2. Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Hui-Wen Chiu

    Full Text Available Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells and PC-3 cells (androgen-independent human prostate cancer cells were used to investigate the anti-cancer effects of ionizing radiation (IR combined with arsenic trioxide (ATO and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen-independent prostate cancer.

  3. STUDY ON EFFECTS OF ARSENIC TRIOXIDE ON GASTRIC CANCER CELL LINES

    Institute of Scientific and Technical Information of China (English)

    顾琴龙; 朱正纲; 洪鹤群; 刘炳亚; 尹浩然; 林言箴; 李宁丽

    2002-01-01

    Objective To evaluate the effects of arsenic trioxide (As2O3) on apoptosis and differentiation of gastric cancer cell lines (GCCL). Methods MKN45 and SGC7901 cells were treated with As2O3 at different concentrations, then the apoptosis rates and cell cycle were determined by flow cytometry assays, the morphologic changes were observed under fluorescence microscopy and electronic microscopy, and the gene expressions were tested with immunohistologic staining. Results Higher apoptosis rates of GCCL were seen in the As2O3-treated group at concentrations of 5μmol and 10μmol, as compared with those in the 5-Fu-treated group. Cell-nuclear pyknosis and chromosomal condensation were observed. The As2O3 at a concentration of 0.5μmol could induce the cell cycle changes of GCCL, revealing an increase in the proportion of G1/G0 phase cells and a decrease in the proportion of S phase cells. From the fifth day after treatment of SGC7901 with As2O3 at a low concentration, P53 and bcl-XL genes expression rates were reduced, Bax gene expression rate increased, and bcl-2 gene expression showed little change. Conclusion As2O3 could induce GCCL apoptosis at a high concentration and differentiation at a low concentration, but it could not completely reverse the malignant biological behaviours of cancer cells.

  4. Endothelial to mesenchymal transition contributes to arsenic-trioxide-induced cardiac fibrosis

    Science.gov (United States)

    Zhang, Yong; Wu, Xianxian; Li, Yang; Zhang, Haiying; Li, Zhange; Zhang, Ying; Zhang, Longyin; Ju, Jiaming; Liu, Xin; Chen, Xiaohui; Glybochko, Peter V.; Nikolenko, Vladimir; Kopylov, Philipp; Xu, Chaoqian; Yang, Baofeng

    2016-01-01

    Emerging evidence has suggested the critical role of endothelial to mesenchymal transition (EndMT) in fibrotic diseases. The present study was designed to examine whether EndMT is involved in arsenic trioxide (As2O3)-induced cardiac fibrosis and to explore the underlying mechanisms. Cardiac dysfunction was observed in rats after exposure to As2O3 for 15 days using echocardiography, and the deposition of collagen was detected by Masson’s trichrome staining and electron microscope. EndMT was indicated by the loss of endothelial cell markers (VE-cadherin and CD31) and the acquisition of mesenchymal cell markers (α-SMA and FSP1) determined by RT-PCR at the mRNA level and Western blot and immunofluorescence analysis at the protein level. In the in-vitro experiments, endothelial cells acquired a spindle-shaped morphology accompanying downregulation of the endothelial cell markers and upregulation of the mesenchymal cell markers when exposed to As2O3. As2O3 activated the AKT/GSK-3β/Snail signaling pathway, and blocking this pathway with PI3K inhibitor (LY294002) abolished EndMT in As2O3-treated endothelial cells. Our results highlight that As2O3 is an EndMT-promoting factor during cardiac fibrosis, suggesting that targeting EndMT is beneficial for preventing As2O3-induced cardiac toxicity. PMID:27671604

  5. Arsenic trioxide induces apoptosis in human platelets via C-Jun NH2-terminal kinase activation.

    Directory of Open Access Journals (Sweden)

    Yicun Wu

    Full Text Available Arsenic trioxide (ATO, one of the oldest drugs in both Western and traditional Chinese medicine, has become an effective anticancer drug, especially in the treatment of acute promyelocytic leukemia (APL. However, thrombocytopenia occurred in most of ATO-treated patients with APL or other malignant diseases, and the pathogenesis remains unclear. Here we show that ATO dose-dependently induces depolarization of mitochondrial inner transmembrane potential (ΔΨm, up-regulation of Bax and down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation, and phosphotidylserine (PS exposure in platelets. ATO did not induce surface expression of P-selectin and PAC-1 binding, whereas, obviously reduced collagen, ADP, and thrombin induced platelet aggregation. ATO dose-dependently induced c-Jun NH2-terminal kinase (JNK activation, and JNK specific inhibitor dicumarol obviously reduced ATO-induced ΔΨm depolarization in platelets. Clinical therapeutic dosage of ATO was intraperitoneally injected into C57 mice, and the numbers of circulating platelets were significantly reduced after five days of continuous injection. The data demonstrate that ATO induces caspase-dependent apoptosis via JNK activation in platelets. ATO does not incur platelet activation, whereas, it not only impairs platelet function but also reduces circulating platelets in vivo, suggesting the possible pathogenesis of thrombocytopenia in patients treated with ATO.

  6. Arsenic trioxide induces apoptosis in human platelets via C-Jun NH2-terminal kinase activation.

    Science.gov (United States)

    Wu, Yicun; Dai, Jin; Zhang, Weilin; Yan, Rong; Zhang, Yiwen; Ruan, Changgeng; Dai, Kesheng

    2014-01-01

    Arsenic trioxide (ATO), one of the oldest drugs in both Western and traditional Chinese medicine, has become an effective anticancer drug, especially in the treatment of acute promyelocytic leukemia (APL). However, thrombocytopenia occurred in most of ATO-treated patients with APL or other malignant diseases, and the pathogenesis remains unclear. Here we show that ATO dose-dependently induces depolarization of mitochondrial inner transmembrane potential (ΔΨm), up-regulation of Bax and down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation, and phosphotidylserine (PS) exposure in platelets. ATO did not induce surface expression of P-selectin and PAC-1 binding, whereas, obviously reduced collagen, ADP, and thrombin induced platelet aggregation. ATO dose-dependently induced c-Jun NH2-terminal kinase (JNK) activation, and JNK specific inhibitor dicumarol obviously reduced ATO-induced ΔΨm depolarization in platelets. Clinical therapeutic dosage of ATO was intraperitoneally injected into C57 mice, and the numbers of circulating platelets were significantly reduced after five days of continuous injection. The data demonstrate that ATO induces caspase-dependent apoptosis via JNK activation in platelets. ATO does not incur platelet activation, whereas, it not only impairs platelet function but also reduces circulating platelets in vivo, suggesting the possible pathogenesis of thrombocytopenia in patients treated with ATO. PMID:24466103

  7. Use of Arsenic Trioxide as an Antivascular and Thermosensitizing Agent in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Robert J. Griffin

    2000-01-01

    Full Text Available Arsenic trioxide, As2O3 (ATO, has been found to be an effective chemotherapy drug for acute promyelocytic leukemia but its effect on solid tumors has not been fully explored. In the present report, we describe our observation that ATO is a potent antivascular agent and that it markedly enhances the effect of hyperthermia on tumors. The tumor blood perfusion in SCK tumors of A/J mice and FSall tumors of C3H mice was significantly suppressed for up to 24 hours after an i.p. injection of 8 mg/kg ATO. ATO was also found to be able to increase the thermosensitivity of tumor cells in vitro. As a probable consequence of these effects, ATO treatment markedly increased the tumor growth delay caused by hyperthermia at 41.5-42.5°C. Immunohistochemical staining of tumor tissue revealed that the expression levels of several adhesion molecules and TNFa are noticeably increased in tumors 2–6 hours after systemic ATO treatment. It is concluded that ATO is potentially useful to enhance the effect of hyperthermia on tumors at a clinically relevant temperature.

  8. Various tolerances to arsenic trioxide between human cortical neurons and leukemic cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jin; MENG Ran; SUI Xinhua; LI Wenbin; YANG Baofeng

    2006-01-01

    Arsenic trioxide (As2O3) is very effective for treatment of acute promyelocytic leukaemia (APL) but little can pass through the blood-brain-barrier (BBB),which limits its use in the prevention and treatment of central nervous system leukaemia (CNSL). Before creating a non-invasive method to help As2O3 's access, the safe and effective therapeutic concentration of As2O3 in the CNS ought to be known. The changes of apoptosis biomarkers, [Ca2+]i and PKC activity of both leukaemia cells and human cortical neurons, were monitored before and after being treated with As2O3 in vitro with laser confocal microscopy and Western blot. NSE concentration, the neuron invasive biomarker, was monitored by enzyme immunoassay (NSE-EIA). This study revealed that cortical neuron was more tolerable to As2O3 compared to NB4. 1.0 μmol / L As2O3 showed little influence on cortical neuron but effectively promoted apoptosis and induced differentiation of NB4.

  9. Differential binding of monomethylarsonous acid compared to arsenite and arsenic trioxide with zinc finger peptides and proteins.

    Science.gov (United States)

    Zhou, Xixi; Sun, Xi; Mobarak, Charlotte; Gandolfi, A Jay; Burchiel, Scott W; Hudson, Laurie G; Liu, Ke Jian

    2014-04-21

    Arsenic is an environmental toxin that enhances the carcinogenic effect of DNA-damaging agents, such as ultraviolet radiation and benzo[a]pyrene. Interaction with zinc finger proteins has been shown to be an important molecular mechanism for arsenic toxicity and cocarcinogenesis. Arsenicals such as arsenite, arsenic trioxide (ATO), and monomethylarsonous acid (MMA(III)) have been reported to interact with cysteine residues of zinc finger domains, but little is known about potential differences in their selectivity of interaction. Herein we analyzed the interaction of arsenite, MMA(III), and ATO with C2H2, C3H1, and C4 configurations of zinc fingers using UV-vis, cobalt, fluorescence, and mass spectrometry. We observed that arsenite and ATO both selectively bound to C3H1 and C4 zinc fingers, while MMA(III) interacted with all three configurations of zinc finger peptides. Structurally and functionally, arsenite and ATO caused conformational changes and zinc loss on C3H1 and C4 zinc finger peptide and protein, respectively, whereas MMA(III) changed conformation and displaced zinc on all three types of zinc fingers. The differential selectivity was also demonstrated in zinc finger proteins isolated from cells treated with these arsenicals. Our results show that trivalent inorganic arsenic compounds, arsenite and ATO, have the same selectivity and behavior when interacting with zinc finger proteins, while methylation removes the selectivity. These findings provide insights on the molecular mechanisms underlying the differential effects of inorganic versus methylated arsenicals, as well as the role of in vivo arsenic methylation in arsenic toxicity and carcinogenesis.

  10. Arsenic trioxide attenuated the rejection of major histocompatibility complex fully-mismatched cardiac allografts in mice.

    Science.gov (United States)

    Yan, S; Zhang, Q Y; Zhou, B; Xue, L; Chen, H; Wang, Y; Zheng, S S

    2009-06-01

    We investigated the effects of arsenic trioxide (As(2)O(3)) on allogeneic immune response using a mouse heart transplantation model. Mice were randomly divided into 4 groups of 6 animals each. The control group received phosphate-buffered saline (PBS); the As(2)O(3)-treated group, intraperitoneal (IP) injection of As(2)O(3) (1 mg/kg) from days -3 to 10 after heart transplantation. The cyclosporine (CsA)-treated group was given a subtherapeutic dose of CsA (10 mg/kg) IP, and the As(2)O(3) plus CsA-treated group, a combined protocol of As(2)O(3) and CsA. Six days after transplantation, cardiac allografts were harvested for immunohistology and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The survival of the allografts was significantly improved among the As(2)O(3)-treated group compared with the control group (17.2 +/- 1.9 vs 8.0 +/- 0.9 days; P < .05). A marked prolongation (28.6 +/- 6.0 days) of graft survival was achieved by the combined protocol compared with the CsA-treated group (9.6 +/- 3.0 days; P < .05) or the As(2)O(3)-treated group. Allografts of As(2)O(3)-treated and As(2)O(3) plus CsA-treated mice showed a changing pattern of Th1/Th2 cytokine mRNA expression. Allograft rejection was apparently alleviated by low-dose As(2)O(3), and particularly when combined with a subtherapeutic CsA dose. PMID:19545743

  11. Combined effect of arsenic trioxide and radiation on physical properties of hemoglobin biopolymer

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    Aisha A. Saad-El-Din

    2014-10-01

    Full Text Available Arsenic trioxide (As2O3 has been recently established as one of the most effective drugs for the treatment of patients with acute promyelocytic leukemia. However, it was widely used in therapeutic of many kinds of cancer by combining it with ionizing radiation. Thus, the purpose of the present study was to explain the combined effect of As2O3 and gamma irradiation on hemoglobin (Hb structure. Measurements using fourier transform infrared (FTIR and UV-visible spectra were done. This study included five groups: control, irradiation with single dose of gamma irradiation of 5 Gy, intraperitonial injection with single dose of 10 mg/kg body weight of As2O3, As2O3+5 Gy and 5 Gy+As2O3. The results reported that the absorbance of secondary amide, amide I and amide II of all groups were lowerd than control, whereas the absorbance of amide III and amide IV for As2O3 and 5 Gy followed by As2O3 injection has been increased. For UV-visible spectra, As2O3 injection decreased the absorbance of globin-heme and soret bands and increased β, α and 630 bands compared with control. On injection with As2O3 followed by 5 Gy showed a decrease in globin-heme, soret, β and α bands and increase in 630 band. Moreover, 5 Gy followed by As2O3 demonestrated a decrease in globin-heme, β, α and 630 bands and an increase in soret band, also the ratio of α/β showed an increase in absorbance compared with control. The results concluded that 5 Gy followed by As2O3 showed some sort of repair in the structure of rats hemoglobin rather than injection with As2O3 and 5 Gy both individually.

  12. Role of Low Dosage Arsenic Trioxide on Pulmonary Dendritic Cells in Asthmatic Mice

    Institute of Scientific and Technical Information of China (English)

    周林福; 殷凯生; 周智敏

    2003-01-01

    Objective: To investigate the distribution and recruitment of pulmonary dendritic cells (DCs) and the influence of low dosage arsenic trioxide (As2O3) on them in the airway of asthmatic mice. Methods: Thirty BALB/c mice were randomly divided into 3 groups: the control group, the asthmatic group and the As2O3 treated group. The mice asthmatic model was induced via sensitizing with peritoneal injection of ovalbumin (OVA) for two times and then provocated with aerosol inhalation of OVA for a week. The treated group was peritoneally injected with 0.2 ml solution of As2O3 (4mg/kg) 0.5h after each provocation. The immunohistochemistry and computerised image analysis were applied to detect quantitatively the DCs in the lung and airway of mice. Results: All intraepithelial nonlymphoid dendritic cells-145 (NLDC-145) throughout the respiratory tree in the mice of the control group formed a network with the density of DCs varying from (575±54) cells/mm2 epithelial surface in the large airway, to (68±12) cells/mm2 epithelial surface in the small airway. The distribution of airway NLDC-145+ in the asthmatic group was similar to that in the control group, but its density was significantly upregulated (P<0.01). The distribution of airway NLDC-145 in the treated group was similar to that in the asthmatic group, only its density was significantly downregulated (P<0.01). Conclusion: There is an integral network of NLDC-145+ throughout the respiratory tree. To downregulate the density but not change the distribution of pulmonary DCs could be an important therapeutic mechanism of low dosage As2O3 in treating asthma.

  13. Proteomic analysis of nuclear matrix proteins during arsenic trioxide induced apoptosis in leukemia K562 cells

    Institute of Scientific and Technical Information of China (English)

    WANG Zi-hui; YU Ding; CHEN Yan; HAO Jian-zhong

    2005-01-01

    Background Arsenic trioxide (As2O3) has been identified as a very potent anti-acute leukemic agent. However its role in apoptosis needs to be elucidated. As2O3 interferes with the proliferation and survival of tumor cells via a variety of mechanisms. Drug-target interactions at the level of nuclear matrix (NM) may be critical events in the induction of cell death by As2O3. This study dealt with As2O3-target interactions at the level of NM in chronic myelogenous leukemia cell line K562 by proteomics. Methods K562 cells were cultured in MEM and treated with different concentrations of As2O3. The nuclear matrix proteins were analyzed by high-resolution two-dimensional gel electrophoresis and computer-assisted image analysis. Results As2O3 significantly inhibited the growth of chronic myelogenous leukemia cell line K562 at low concentrations. While more than 200 protein spots were shared among the nuclear matrices, about 18 distinct spots in the nuclear matrices were found characteristic for As2O3 treated cells. Conclusions: As2O3 induces apoptosis in K562 cells in a dose and time-dependent manner. Our results demonstrated that for the detection of the onset of apoptosis, the alteration in the composition of nuclear matrix proteins was a more sensitive indicator than nucleosomal DNA fragmentation test. These results indicated that As2O3 might be clinically useful in the treatment of chronic myelogenous leukemia. The changes of nuclear matrix proteins in the treated cells can be used as a useful indicator for this treatment.

  14. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells

    International Nuclear Information System (INIS)

    Highlights: • As2O3 inhibits growth of cervical cancer cells and expression of HPV oncogenes in these cells. • HPV-negative cervical cancer cells are more sensitive to As2O3 than HPV-positive cervical cancer cells. • HPV-18 positive cervical cancer cells are more sensitive to As2O3 than HPV-16 positive cancer cells. • Down-regulation of HPV oncogenes by As2O3 is partially due to the diminished AP-1 binding. - Abstract: Arsenic trioxide (As2O3) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As2O3 induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As2O3 on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As2O3 than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As2O3 than HPV 16-positive CaSki and SiHa cells. After As2O3 treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As2O3 is a potential anticancer drug for cervical cancer

  15. Studies on arsenic trioxide induced mice melanoma Cloundman S91 cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Ruzhi Zhang; Wenyuan Zhu; Chen Wang

    2005-01-01

    Objective: To invesfgate the effects of various concentrations As2O3 on malignant melanoma. Methods: The viability of Cloundman melanoma S91 cells treated with As2O3 was measured by MTT [3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide] assay. The apoptosis was determined by transferase-mediated dUTP nick end labeling (TUNEL) detection, and the morphology of apoptotic cells was observed through transmission electron microscopy (TEM). The cells growth phase were analyzed by flow cytometry (FCM). Results: A time-and dose-dependent decrease in cell viability was induced in S91 cells after treatment with As2Os at the concentration of 1-5 μmol/L respectively. The TUNEL indices were 0.033 ± 0.018, 0.062 ± 0.012, 0.102 ± 0.016, 0.132 ± 0.031,and 0.162 ± 0.027 respectively, which were much higher compared with the control group (0.017 ± 0.004, P < 0.01). The flow cytometry showed that hypodiploid peak after treatment with 3 μmol/L and 5 μmol/L of As2O3 for 48 h were 9.99% and 17.59% respectively,which increased significantly compared with the control cells (3.05% P < 0.01, ). The apoptotic morphology observed by transmission electron microscope showed the chromatin became condensed and attached to the inner surface of nuclear membrane. Conclusion: Arsenic trioxide can induce melanoma Cloundman S91 cell apoptosis at the concentration of 1-5 μmol/L, which will provide enhanced benefit in melanoma therapy.

  16. Effects of Arsenic Trioxide on Human Renal Cell Carcinoma Lines in Vitro

    Institute of Scientific and Technical Information of China (English)

    屈凤莲; 李艳芬; 万云霞; 马建辉; 石卫; 储大同; 孙燕

    2004-01-01

    Objective: To observe the effects of arsenic trioxide (As2O3) on human renal cell carcinoma (RCC) lines in vitro and to explore its possible molecular mechanisms. Methods: The microculture tetrazolium (MTT) assay was used to determine the anti-proliferative effects of As2O3 on human RCC lines. Flow cytometry was performed to investigate the effects of As2O3 on cell cycle and cell apoptosis. The reverse transcription-polymerase chain reaction (RT-PCR) was conducted to detect mRNA expression of Bcl-2, Bax, p53and c-myc. Results: As2O3 inhibited the growth of RCC lines in vitro in a concentration-dependent manner. At the concentrations of 0.5, 1.0, 2.0 and 4.0 μmol/L, the inhibition rates of As2O3 on RCC-WCS cells were 27.60%, 30.09%, 41.03% and 50.77%, respectively. Compared with untreated RCC-WCS, there was significant difference at each concentration (P<0.01). As2O3 induced a G1 phase arrest in RCC-LSL cells,but a G2/M phase arrest in RCC-WCS and RCC-SHK. As2O3 induced cell apoptosis in these cell lines. The mRNA level of p53 and c-myc decreased, but no detectable changes of Bcl-2 and Bax were observed after As2O3 treatmen. Conclusion: As2O3 in therapeutic concentrations inhibited the in vitro growth of RCC lines via cell cycle arrest and apoptosis. One of its possible mechanisms was down-regulation of p53 and c-myc. Our results suggest that As2O3 is probably a new candidate agent for the treatment of human renal carcinoma.

  17. Effects of Arsenic Trioxide on Human Renal Cell Carcinoma Lines in Vitro

    Institute of Scientific and Technical Information of China (English)

    屈凤莲; 李艳芬; 万云霞; 马建辉; 石卫; 储大同; 孙燕

    2004-01-01

    Objective: To observe the effects of arsenic trioxide (As2O3) on human renal cell carcinoma (RCC) lines in vitro and to explore its possible molecular mechanisms. Methods. The microculture tetrazolium (MTT) assay was used to determine the anti-proliferative effects of As2O3 on human RCC lines. Flow cytometry was performed to investigate the effects of As2O3 on cell cycle and cell apoptosis. The reverse transcription-polymerase chain reaction (RT-PCR) was conducted to detect mRNA expression of Bcl-2, Bax, p53 and c-myc. Results: As2O3 inhibited the growth of ROC lines in vitro in a concentration-dependent manner. At the concentrations of 0.5, 1.0, 2.0 and 4.0μmol/L, the inhibition rates of As2O3 on RCC-WCS cells were 27.60%, 30.09%, 41.03% and 50.77%, respectively. Compared with untreated RCC-WCS, there was significant difference at each concentration (P<0.01). As2O3 induced a G1 phase arrest in RCC-LSL cells, but a G2/M phase arrest in RCC-WCS and RCC-SHK. As2O3 induced cell apoptosis in these cell lines. The mRNA level of p53 and c-myc decreased, but no detectable changes of Bcl-2 and Bax were observed after As2O3 treatmen. Conclusion. As2O3 in therapeutic concentrations inhibited the in vitro growth of RCC lines via cell cycle arrest and apoptosis. One of its possible mechanisms was down-regulation of p53 and c-myc. Our results suggest that As2O3 is probably a new candidate agent for the treatment of human renal carcinoma.

  18. TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA WITH SINGLE-AGENT ARSENIC TRIOXIDE

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    Vikram Mathews

    2011-11-01

    Full Text Available It is well recognized that arsenic trioxide (ATO is an efficacious agent for the treatment of acute promyelocytic leukemia (APL. Use of single agent ATO in the treatment of APL leads to remissions which are durable in the majority. ATO is probably the most effective single agent in the treatment of APL and there have been very few reports of primary resistance. It has been used both as a single agent and in combination with other conventional drugs to treat APL. Use of ATO is the accepted standard of care in the management of relapsed APL, where it is often used effectively as a bridge to a stem cell transplant. However, its role in newly diagnosed APL remains controversial. ATO probably has multiple mechanisms of action. Better understanding of its mechanisms of action/s is likely to lead to more rationale use of this agent or its derivatives either alone or in combination with other drugs. There is limited data on the kinetics of leukemia clearance and normal haematopoietic recovery after the administration of single agent ATO for the treatment of APL, preliminary data suggests that it is likely to be different from conventional therapy. There have been a number of concerns of the potential short and long term toxicity of this agent. Most such concerns arise from the toxicity profile noted in people exposed to long term arsenic exposure in the environment. With the therapeutic doses and schedules of administration of ATO in the treatment of malignancies the overall toxicity profile has been favorable. In a resource constrained environments the use of a single agent ATO based regimen is a realistic and acceptable option to treat almost all patients. In the developed world it has the potential in combination with other agents to improve the clinical outcome with reduction of dose intensity of chemotherapy and remains an option for patients who would not tolerate conventional therapy. In this review we focus on the use of single agent ATO for the

  19. A facile route to core-shell nanoparticulate formation of arsenic trioxide for effective solid tumor treatment

    Science.gov (United States)

    Zhang, Zongjun; Liu, Hanyu; Zhou, Hualu; Zhu, Xianglong; Zhao, Zhenghuan; Chi, Xiaoqin; Shan, Hong; Gao, Jinhao

    2016-02-01

    Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a ``one-pot'' method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core-shell embedding method endows nanodrugs with high loading capacity (57.9 wt%) and a prolonged pH-responsive releasing profile, which is crucial to increase the drug concentration at tumor sites and improve the drug efficacy. Based on these unique features, the nanodrugs significantly inhibit the growth of solid tumors without adverse side effects. Therefore, we anticipate that the arsenic-based nanodrugs generated by this facile synthetic route may be a powerful and alternative strategy for solid tumor therapy.Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a ``one-pot'' method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core-shell embedding method endows nanodrugs with high loading capacity

  20. Arsenic Trioxide Attenuates NF-κB and Cytokine mRNA Levels in the Livers of Cocks.

    Science.gov (United States)

    Zhang, Kexin; Zhao, Panpan; Guo, Guangyang; Guo, Ying; Tian, Li; Sun, Xiao; Li, Siwen; He, Ying; Sun, Ying; Chai, Hongliang; Zhang, Wen; Xing, Mingwei

    2016-04-01

    Arsenic (As) is a trace element widely found in nature. It exists in several forms, including organic arsenic, inorganic arsenic, and trivalent arsenic, the most toxic. Arsenic trioxide (As2O3) is widespread in nature. This form tends to accumulate in animals and humans and therefore has a potential harm for them. Cytokines play essential roles in the immune response and inflammation. Although the importance of cytokines in the responses to arsenic exposure has been demonstrated in many types of mammals, the function of these in poultry, especially in chickens, remains unclear. The purpose of the present study was to examine the effect of As2O3 exposure on cytokines in cock livers. In this study, 72 1-day-old male Hy-line cocks were randomly divided into four groups including the control group, low-As group, middle-As group, and high-As group. The livers were collected on days 30, 60, and 90 of the experiment. The levels of nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-12 beta (IL-12β), and interleukin-1 beta (IL-1β) mRNA in the livers of the cocks were measured using real-time PCR. The results showed that the expression levels of IL-6, IL-8, TNF-α, and NF-κB which seemed to be a critical mediator in the inflammatory response tended to increase in the birds chronically treated with As2O3. However, the mRNA expression levels of IL-4, IL-12β, and IL-1β were decreased in the experiment. The information regarding the effects of As2O3 on cytokine mRNA expression generated in this study will be important information for arsenic toxicology evaluation. PMID:26276563

  1. ETME, a novel β-elemene derivative, synergizes with arsenic trioxide in inducing apoptosis and cell cycle arrest in hepatocarcinoma cells via a p53-dependent pathway

    Directory of Open Access Journals (Sweden)

    Zhiying Yu

    2014-12-01

    Full Text Available Arsenic trioxide (ATO has been identified as an effective treatment for acute promyelocytic leukemia (APL but is much less effective against solid tumors such as hepatocellular carcinoma (HCC. In the search for ways to enhance its therapeutic efficacy against solid tumors, we have examined its use in combination with a novel derivative of β-elemene, N-(β-elemene-13-yltryptophan methyl ester (ETME. Here we report the effects of the combination on cell viability, apoptosis, the cell cycle and mitochondria membrane potential (MMP in HCC SMMC-7721 cells. We found that the two compounds acted synergistically to enhance antiproliferative activity and apoptosis. The combination also decreased the MMP, down-regulated Bcl-2 and pro-proteins of the caspase family, and up-regulated Bax and BID, all of which were reversed by the p53 inhibitor, pifithrin-α. In addition, the combination induced cell cycle arrest at the G2/M phase and reduced tumor volume and weight in an xenograft model of nude mice. Overall, the results suggest that ETME in combination with ATO may be useful in the treatment of HCC patients particularly those unresponsive to ATO alone.

  2. Addition of Arsenic Trioxide into Induction Regimens Could Not Accelerate Recovery of Abnormality of Coagulation and Fibrinolysis in Patients with Acute Promyelocytic Leukemia.

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    Ye Zhang

    Full Text Available All-trans retinoic acid combined to anthracycline-based chemotherapy is the standard regimen of acute promyelocytic leukemia. The advent of arsenic trioxide has contributed to improve the anti-leukemic efficacy in acute promyelocytic leukemia. The objectives of the current study were to evaluate if dual induction by all-trans retinoic acid and arsenic trioxide could accelerate the recovery of abnormality of coagulation and fibrinolysis in patients with acute promyelocytic leukemia.Retrospective analysis was performed in 103 newly-diagnosed patients with acute promyelocytic leukemia. Hemostatic variables and the consumption of component blood were comparably analyzed among patients treated by different induction regimen with or without arsenic trioxide.Compared to patients with other subtypes of de novo acute myeloid leukemia, patients with acute promyelocytic leukemia had lower platelet counts and fibrinogen levels, significantly prolonged prothrombin time and elevated D-dimers (P<0.001. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification presented lower initial fibrinogen level than that of low-risk group (P<0.05. After induction treatment, abnormal coagulation and fibrinolysis of patients with acute promyelocytic leukemia was significantly improved before day 10. The recovery of abnormal hemostatic variables (platelet, prothrombin time, fibrinogen and D-dimer was not significantly accelerated after adding arsenic trioxide in induction regimens; and the consumption of transfused component blood (platelet and plasma did not dramatically change either. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification had higher platelet transfusion demands than that of low-risk group (P<0.05.Unexpectedly, adding arsenic trioxide could not accelerate the recovery of abnormality of coagulation and fibrinolysis in acute promyelocytic leukemia patients who received all

  3. Downregulation of thymidylate synthase and E2F1 by arsenic trioxide in mesothelioma.

    Science.gov (United States)

    Lam, Sze-Kwan; Li, Yuan-Yuan; Zheng, Chun-Yan; Ho, James Chung-Man

    2015-01-01

    Malignant pleural mesothelioma is a global health issue. Arsenic trioxide (ATO) has been shown to suppress thymidylate synthase (TYMS) in lung adenocarcinoma and colorectal cancer, and induce apoptosis in acute promyelocytic leukemia. With TYMS as a putative therapeutic target, the effect of ATO in mesothelioma was therefore studied. A panel of 5 mesothelioma cell lines was used to study the effect of ATO on cell viability, protein expression, mRNA expression and TYMS activity by MTT assay, western blot, qPCR and tritium-release assay, respectively. The knockdown of TYMS and E2F1 was performed with a specific siRNA. Phosphatidylserine externalization and mitochondrial membrane depolarization were measured by Annexin V and JC-1 staining respectively. The in vivo effect of ATO was studied using a nude mouse xenograft model. Application of ATO demonstrated anticancer effects in the cell line model with clinically achievable concentrations. Downregulation of TYMS protein (except H226 cells and 1.25 µM ATO in H2052 cells) and mRNA expression (H28 cells), pRB1 (H28 cells) and E2F1 and TYMS activity (except H226 cells) were also evident. E2F1 knockdown decreased cell viability more significantly than TYMS knockdown. In general, thymidine kinase 1, ribonucleotide reductase M1, c-myc and skp2 were downregulated by ATO. p-c-Jun was downregulated in H28 cells while upregulated in 211H cells. Phosphatidylserine externalization, mitochondrial membrane depolarization, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bak and cleaved caspase-3 were observed. In the H226 xenograft model, the relative tumor growth was aborted, and E2F1 was downregulated while cleaved caspase-3 was elevated and localized to the nucleus in the ATO treatment group. ATO has potent antiproliferative and cytotoxic effects in mesothelioma in vitro and in vivo, partially mediated through E2F1 targeting (less effect through TYMS targeting). There is sound scientific evidence to support the

  4. Activity of Nanobins Loaded with Cisplatin and Arsenic Trioxide in Primary and Metastatic Breast Cancer

    Science.gov (United States)

    Swindell, Elden Peter, III

    Despite recent advances in breast cancer screening and detection, the disease is still a leading cause of death for women of all ages. Young, African-American women are disproportionally affected with a type of breast cancer, triple-negative breast cancer, which is particularly difficult to treat and has the worst prognosis of any breast cancer subtype. These tumors often spread to the lungs, liver, bones and brains of patients, which is ultimately fatal. This dissertation presents results from a series of in vivo and in vitro experiments that investigate the clinical utility of a novel nanoparticulate formulation of cisplatin and arsenic trioxide, NB(Pt,As) for treating primary and metastatic triple-negative breast cancer. These nanobins consist of a solid, crystalline metal nanoparticle surrounded by a lipid bilayer with 80-90 nm diameter. This drug payload is extremely stable, and so NB(Pt,As) is extremely well tolerated in mice. Furthermore, NB(Pt,As) is effective in two different mouse models of breast cancer, one of primary tumor growth an another of lung metastases. A discovery presented here, that thiol containing compounds are required for drug release, may explain these seemingly incongruous results. The large amount of intracellular thiol can trigger drug release, while the low concentration of free thiols in blood is insufficient to cause drug release. To improve the treatment of brain tumors with this unique drug, we added transferrin to the surface of the nanobin using copper-catalyzed "click" chemistry, which preserves protein activity. The addition of transferrin to the nanobins enables 10 fold greater uptake in the brains of mice treated with the transferrin-targeted nanobins Tf-NB(Pt,A) compared to NB(Pt,As). By penetrating the blood brain barrier, the Tf-NB(Pt,As) was able to reduce breast cancer metastases in the brains of mice, whereas NB(Pt,As) had no effect. Taken together, these results demonstrate the intricate balance of drug release

  5. Induction of apoptosis by arsenic trioxide and hydroxycamptothecin in gastric cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Jie Zhong; JI Hong Tan; Xiao Hua Jiang; Min Min Qiao; Yu Xin Wu; Shi Hu Jiang; ShuiPing Tu

    2000-01-01

    AIM To study the effects of arsenic trioxide and HCPT on different degrees of differentiated gastric cancer cells (SGC-7901, MKN-45, MKN-28)with respect to both cytotoxicity and induction of apoptosis in vitro. ~ODS The cytotoxicity of As2O3 and HCPT on gastric cancer cells was determined by MTTassay. Morphologic changes of apoptosis of gastric cancer cells were observed by light microscopy and transmission electron microscopy. Apoptosis and cell cycle changes of gastric cancer cells induced by HCPT and As2O3 were investigated by TUNEL method and flow cytometry. RESULTS As2O3 and HCPT had remarkable cytotoxic effects on different degrees of differentiated gastric cancer cells. The IC50 of As2O3 on well differentiated gastric cancer cell MKN-28, moderately differentiated gastric cancer cell SGC-7901, and poorly differentiated gastric cancer cell MKN-28 were 8. 91 μmol/L, 10. 57 μmol/L, and 11.65 μmol/L, respectively. The IC50 of HCPT on MKN-28, SGC-7901, and MKN-45 were 9. 35 rg/L, 10. 21 rg/L, and 12. 63 mg/L respectively after 48 h treatment. After 12 h of exposure to both drugs, gastric cancer cells exhibited morphologic features of apoptosis, including cell shrinkage, nuclear condensation,and formation of apoptotic bodies. A typical subdiploid peak before G0/G1 phase was observed by flow cytometry. The apoptotic rates of SGC7901, MKN-45, and MKN-28 were 13. 84%, 22.52%, and 9. 68%, respectively after 48 h exposure to 10 μmol/L As2O3. The apoptotic rates of SGC-7901, MKN-45, and MKN-28 were 21.88%, 12.35%, and 30. 26%, respectively after 48 h exposure to 10 mg/L HCPT. The apoptotic indice were 7% - 15% as assessed by TUNEL method. The effect of As2O3 on SGC-7901 showed remarkable cell cycle specificity, which induced cell death in G1 phase, and blocked G2/M phase. HCPT also showed a remarkable cell cycle specificity, by inducing cell death and apoptosis in G1 phase and arrest of proliferation at S phase. CONCLUSION AS2O3 and HCPT exhibit significant

  6. Matrix metalloproteinase-9 is involved in chronic lymphocytic leukemia cell response to fludarabine and arsenic trioxide.

    Directory of Open Access Journals (Sweden)

    Irene Amigo-Jiménez

    Full Text Available BACKGROUND: Matrix metalloproteinase-9 (MMP-9 contributes to chronic lymphocytic leukemia (CLL pathology by regulating cell migration and preventing spontaneous apoptosis. It is not known if MMP-9 is involved in CLL cell response to chemotherapy and we address this in the present study, using arsenic trioxide (ATO and fludarabine as examples of cytotoxic drugs. METHODS: We used primary cells from the peripheral blood of CLL patients and MEC-1 cells stably transfected with an empty vector or a vector containing MMP-9. The effect of ATO and fludarabine was determined by flow cytometry and by the MTT assay. Expression of mRNA was measured by RT-PCR and qPCR. Secreted and cell-bound MMP-9 was analyzed by gelatin zymography and flow cytometry, respectively. Protein expression was analyzed by Western blotting and immunoprecipitation. Statistical analyses were performed using the two-tailed Student's t-test. RESULTS: In response to ATO or fludarabine, CLL cells transcriptionally upregulated MMP-9, preceding the onset of apoptosis. Upregulated MMP-9 primarily localized to the membrane of early apoptotic cells and blocking apoptosis with Z-VAD prevented MMP-9 upregulation, thus linking MMP-9 to the apoptotic process. Culturing CLL cells on MMP-9 or stromal cells induced drug resistance, which was overcome by anti-MMP-9 antibodies. Accordingly, MMP-9-MEC-1 transfectants showed higher viability upon drug treatment than Mock-MEC-1 cells, and this effect was blocked by silencing MMP-9 with specific siRNAs. Following drug exposure, expression of anti-apoptotic proteins (Mcl-1, Bcl-xL, Bcl-2 and the Mcl-1/Bim, Mcl-1/Noxa, Bcl-2/Bax ratios were higher in MMP-9-cells than in Mock-cells. Similar results were obtained upon culturing primary CLL cells on MMP-9. CONCLUSIONS: Our study describes for the first time that MMP-9 induces drug resistance by modulating proteins of the Bcl-2 family and upregulating the corresponding anti-apoptotic/pro-apoptotic ratios. This

  7. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongtao [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China); Gao, Peng [Department of Internal Medicine, University of Iowa, Iowa City, IA 52242 (United States); Zheng, Jie, E-mail: jiezheng54@126.com [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China)

    2014-09-05

    Highlights: • As{sub 2}O{sub 3} inhibits growth of cervical cancer cells and expression of HPV oncogenes in these cells. • HPV-negative cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-positive cervical cancer cells. • HPV-18 positive cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-16 positive cancer cells. • Down-regulation of HPV oncogenes by As{sub 2}O{sub 3} is partially due to the diminished AP-1 binding. - Abstract: Arsenic trioxide (As{sub 2}O{sub 3}) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As{sub 2}O{sub 3} induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As{sub 2}O{sub 3} on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As{sub 2}O{sub 3} than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As{sub 2}O{sub 3} than HPV 16-positive CaSki and SiHa cells. After As{sub 2}O{sub 3} treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As{sub 2}O{sub 3} is a potential anticancer drug for cervical cancer.

  8. Effect of arsenic trioxide on rat hepatocarcinoma and its renal cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Shao-Shan Wang; Ti Zhang; Xi-Lu Wang; Li Hong; Qing-Hui Qi

    2003-01-01

    AIM: To study the effect of arsenic trioxide (As2O3) on rat experimental hepatocarcinoma and its renal cytotoxicity.METHODS: The hepatocarcinoma model was established by diethaylnitrosamine perfusion in stomach of 120 Wistar rats, and the treatment began at the end of 20 weeks.Before the treatment, the rat models were randomly divided into 5 groups. In the treatment groups, three doses of As2O3 were injected into rat abdominal cavity, the total time of drug administration was 4 weeks. Cisplatin control or the blank group was injected into abdominal cavity with equal amount of cisplatin or saline at the same time,respectively. On the 7th, 14th and 28th day after the treatment, the hepatocarcinoma nodules were obtained and the morphologic changes of hepatocarcinoma cells were observed under light and electron microscopes;Immunohistochemistry (S-P methods) was employed to detect the expression of bcl-2, bax and PCNA in hepatocarcinoma tissues; flow cytometry (TUNEL assay)was used to detect the apoptosis of liver cancer cells and the change of cytokinetics. On the 28th day, the kidneys were obtained and their histologic changes were observed under light microscope, and immunohistochemistry (SP stain) was also employed to detect the expression of bcl-2and PCNA. Cisplatin and saline solution were used as the control.RESULTS: As2O3 could induce the apoptosis of rat liver cancer cells and exhibited typical morphologic changes.The incidence of apoptosis of hapatocarcinoma cells was elevated (P=0.001). The elevation was the most higher in the group of middle-dose of As2O3 (1 mg.kg-1), significantly higher than that of the other arsenic groups and the controls (P=0.001). Large dose of As2O3 (5 mg.kg-1) was able to arise the incidence of apoptosis, but also produced a large amount of necrosis and inflammatory reaction. Middle dose of As2O3 dramatically increased the cell number in G2/M phase (P=0.0001), and apoptosis happened apparently.The expression of bcl-2 and bax was

  9. Nrf2 activation ameliorates cytotoxic effects of arsenic trioxide in acute promyelocytic leukemia cells through increased glutathione levels and arsenic efflux from cells.

    Science.gov (United States)

    Nishimoto, Shoichi; Suzuki, Toshihiro; Koike, Shin; Yuan, Bo; Takagi, Norio; Ogasawara, Yuki

    2016-08-15

    Carnosic acid (CA), a phenolic diterpene isolated from Rosmarinus officinalis, has been shown to activate nuclear transcription factor E2-related factor 2 (Nrf2), which plays a central role in cytoprotective responses to oxidative and electrophilic stress. Recently, the Nrf2-Kelch ECH associating protein 1 (Keap1) pathway has been associated with cancer drug resistance attributable to modulation of the expression and activation of antioxidant and detoxification enzymes. However, the exact mechanisms by which Nrf2 activation results in chemoresistance are insufficiently understood to date. This study investigated the mechanisms by which the cytotoxic effects of arsenic trioxide (ATO), an anticancer drug, were decreased in acute promyelocytic leukemia cells treated with CA, a typical activator of Nrf2 used to stimulate the Nrf2/Keap1 system. Our findings suggest that arsenic is non-enzymatically incorporated into NB4 cells and forms complexes that are dependent on intracellular glutathione (GSH) concentrations. In addition, the arsenic complexes are recognized as substrates by multidrug resistance proteins and subsequently excreted from the cells. Therefore, Nrf2-associated activation of the GSH biosynthetic pathway, followed by increased levels of intracellular GSH, are key mechanisms underlying accelerated arsenic efflux and attenuation of the cytotoxic effects of ATO. PMID:27317373

  10. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  11. Refractory acute promyelocytic leukemia successfully treated with combination therapy of arsenic trioxide and tamibarotene: A case report

    Directory of Open Access Journals (Sweden)

    Minoru Kojima

    2016-01-01

    Full Text Available A 40-year-old male developed refractory acute promyelocytic leukemia (APL after various treatments including all-trans retinoic acid, tamibarotene, arsenic trioxide (As2O3, conventional chemotherapy, and autologous peripheral blood stem cell transplantation. We attempted to use both tamibarotene and As2O3 as a combination therapy, and he achieved molecular complete remission. Grade 2 prolongation of the QTc interval on the electrocardiogram was observed during the therapy. The combination therapy of As2O3 and tamibarotene may be effective and tolerable for treating refractory APL cases who have no treatment options, even when they have previously been treated with tamibarotene and As2O3 as a single agent.

  12. Effects of arsenic trioxide on voltage-dependent potassium channels and on cell proliferation of human multiple myeloma cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jin; WANG Wei; WEI Qing-fang; FENG Tie-ming; TAN Li-jun; YANG Bao-feng

    2007-01-01

    @@ Arsenic trioxide (ATO) can induce cellular apoptosis and inhibit the activities of multiple myeloma (MM)cells in vitro,1 but how it works is not very clear. Recent studies showed that ATO worked on the voltagedependent potassium channel and L-type calcium channel in myocardial cells,2-5 but the effect of ATO on ion channels of tumor cells was rarely reported. As the potassium channel plays an important role in controlling cell proliferation,6 we studied the effects of ATO on the voltage-dependent potassium current (Ikv) of the voltage-dependent potassium channel in an MM cell line,and probed into the relationship between changes of the Ikv caused by ATO and cell proliferation.

  13. Nuclear matrix associated protein PML: an arsenic trioxide apoptosis therapeutic target protein in HepG2 cells

    Institute of Scientific and Technical Information of China (English)

    于鼎; 王子慧; 朱立元; 邱殷庆

    2003-01-01

    Objective To investigate arsenic trioxide (As2O3)-induced apoptosis and the effects on cell nuclear matrix related protein promyelocytic leukaemia (PML). Methods HepG2 cells were cultured in MEM medium and treated with 0.5, 2, 5 and 10 μmol/L As2O3 for either 24 h or 96 h at each concentration. In situ terminal deoxynucleotidyl transferase (TdT) labeling (TUNEL) and DNA ladders were used to detect apoptosis. Confocal microscopy and Western blotting were used to observe the expression of PML. Results The growth rates of HepG2 cells were slower in the As2O3 treated than the untreated control group. DNA ladder and TUNEL positive apoptotic cells could be detected in As2O3 treated groups. The expression of PML decreased in HepG2 cells with 2 μmol/L As2O3 treatment. Confocal images demonstrated that the expression of PML protein in HepG2 cell nuclei decreased after treatment with 2 μmol/L As2O3, and micropunctates characteristic of PML protein in HepG2 cell nuclei disappeared after treatment with 5 μmol/L As2O3.Conclusions Our results show that arsenic trioxide can significantly inhibit the growth of HepG2 cells in vitro. As2O3 induces apoptosis in HepG2 tumor cells in a time and concentration dependent manner. As2O3 may degrade the PML protein in HepG2 cell nuclei. The decreased expression of PML in As2O3 treated tumor cells is most likely to be caused by apoptosis. Nuclear matrix associated protein PML could be the target of As2O3 therapy.

  14. Ebb-and-flow of macroautophagy and chaperone-mediated autophagy in Raji cells induced by starvation and arsenic trioxide.

    Science.gov (United States)

    Li, Cai-Li; Wei, Hu-Lai; Chen, Jing; Wang, Bei; Xie, Bei; Fan, Lin-Lan; Li, Lin-Jing

    2014-01-01

    Autophagy is crucial in the maintenance of homeostasis and regenerated energy of mammalian cells. Macroautophagy and chaperone-mediated autophagy(CMA) are the two best-identified pathways. Recent research has found that in normal cells, decline of macroautophagy is appropriately parallel with activation of CMA. However, whether it is also true in cancer cells has been poorly studied. Here we focused on cross-talk and conversion between macroautophagy and CMA in cultured Burkitt lymphoma Raji cells when facing serum deprivation and exposure to a toxic compound, arsenic trioxide. The results showed that both macroautophagy and CMA were activated sequentially instead of simultaneously in starvation-induced Raji cells, and macroautophagy was quickly activated and peaked during the first hours of nutrition deprivation, and then gradually decreased to near baseline. With nutrient deprivation persisted, CMA progressively increased along with the decline of macroautophagy. On the other hand, in arsenic trioxide-treated Raji cells, macroautophagy activity was also significantly increased, but CMA activity was not rapidly enhanced until macroautophagy was inhibited by 3-methyladenine, an inhibitor. Together, we conclude that cancer cells exhibit differential responses to diverse stressor-induced damage by autophagy. The sequential switch of the first-aider macroautophagy to the homeostasis-stabilizer CMA, whether active or passive, might be conducive to the adaption of cancer cells to miscellaneous intracellular or extracellular stressors. These findings must be helpful to understand the characteristics, compensatory mechanisms and answer modes of different autophagic pathways in cancer cells, which might be very important and promising to the development of potential targeting interventions for cancer therapies via regulation of autophagic pathways. PMID:25081691

  15. Arsenic trioxide up-regulates Fas expression in human osteosarcoma cells

    Institute of Scientific and Technical Information of China (English)

    YANG Guo-fu; LI Xiang-hui; ZHAO Zhe; WANG Wen-bo

    2010-01-01

    Background Osteosarcoma is a common primary malignant tumor of bone with a poor prognosis due to its propensity for metastasis. The prognosis of patients is highly dependent on the presence or absence of lung metastasis and on the effectiveness of treatment against it. It has been reported that low level expression of Fas protein in human osteosarcoma cell is closely associated with lung metastasis. A large number of studies have shown that arsenic trioxide (ATO) can inhibit proliferation and induce apoptosis of many cancer cell lines; however, its effects on human osteosarcoma cells (Saos-2 cell line) remains unknown. The aim of this study was to investigate the effects of ATO on Saos-2 cells and to characterize its mechanism of Fas-expressing.Methods A group of Saos-2 cells was treated with or without 0.5,1,2,4 and 8 urnol/L ATO for three successive days, and the cytotoxicity of ATO was determined by an 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological changes in cells were studied by acridine orange/ethidium bromide (AO/EB) double staining. Flow cytometry (FCM) was used to assay cell DNA distribution. Another group of cells was pretreated with 10 nmol/L matrix metalloproteinase 7 (MMP-7) for 3 hours. They were then incubated with or without 2 umol/L ATO for 24, 48 and 72 hours. Cytotoxicity, Fas protein and mRNA levels were systematically studied using MTT, Western blotting and real-time PCR, respectively. Cell proliferation, cell cycle progression and apoptosis were examined in this study. Results Proliferation of Saos-2 cells was inhibited by ATO in both a dose- and time-dependent manner. The IC50 values at 24, 48 and 72 hours were 9.30, 5.54 and 3.49 μmol/L, respectively. The survival rate of Saos-2 cells in the MMP-7 and ATO co-treated group was significantly higher than the ATO group, but it was lower than the control group. ATO induced G1 phase arrest of the cell cycle and very efficiently stimulated apoptosis in Saos

  16. Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells.

    Science.gov (United States)

    Zeng, Yingjian; Weng, Guangyang; Fan, Jiaxin; Li, Zhangqiu; Wu, Jianwei; Li, Yuanming; Zheng, Rong; Xia, Pingfang; Guo, Kunyuan

    2016-09-01

    Low response, treatment-related complications and relapse due to the low sensitivity of myelodysplastic syndrome (MDS) and leukemia stem cells (LSCs) or pre‑LSCs to arsenic trioxide (ATO), represent the main problems following treatment with ATO alone in patients with MDS. To solve these problems, a chemosensitization agent can be applied to increase the susceptibility of these cells to ATO. Curcumin (CUR), which possesses a wide range of anticancer activities, is a commonly used chemosensitization agent for various types of tumors, including hematopoietic malignancies. In the present study, we investigated the cytotoxic effects and potential mechanisms in MDS-SKM-1 and leukemia stem-like KG1a cells treated with CUR and ATO alone or in combination. CUR and ATO exhibited growth inhibition detected by MTT assays and apoptosis analyzed by Annexin V/PI analyses in both SKM-1 and KG1a cells. Apoptosis of SKM-1 and KG1a cells determined by Annexin V/PI was significantly enhanced in the combination groups compared with the groups treated with either agent alone. Further evaluation was performed by western blotting for two hallmark markers of apoptosis, caspase-3 and cleaved-PARP. Co-treatment of the cells with CUR and ATO resulted in significant synergistic effects. In SKM-1 and KG1a cells, 31 and 13 proteins analyzed by protein array assays were modulated, respectively. Notably, survivin protein expression levels were downregulated in both cell lines treated with CUR alone and in combination with ATO, particularly in the latter case. Susceptibility to apoptosis was significantly increased in SKM-1 and KG1a cells treated with siRNA-survivin and ATO. These results suggested that CUR increased the sensitivity of SKM-1 and KG1a cells to ATO by downregulating the expression of survivin. PMID:27430728

  17. Mechanisms of arsenic trioxide induced apoptosis of human cervical cancer HeLa cells and protection by Bcl-2

    Institute of Scientific and Technical Information of China (English)

    邓友平; 林晨; 郑杰; 梁萧; 陈洁平; 付明; 肖培根; 吴旻

    1999-01-01

    It was recently reported that arsenic trioxide (As2O3) can induce complete remission in patients with acute promyelocytic leukemia (APL). In this present article, the biological effect of As2O3 on human cervical cancer HeLa cells and HeLa cells overexpressing Bcl-2 is studied. By MTT and colony forming ability assays, morphology alteration, flow cytometric analysis, DNA gel electrephoresis and in situ cell death detection (TUNEL), it was found that As2O3 inhibited the growth of HeLa cells and induced G2/M arrest and apoptosis of the cells. RT-PCR, Northern blot, Western blot analysis revealed that As2O3 induced HeLa cell apoptosis possibly via decreasing the expression of c-myc and viral genes. HeLa cells overexpressing Bcl-2 partly resist As2O3 induced apoptosis, which might be relative to preventing the cells from As2O3 caused G2/M block, downregulation of c-myc gene expression and inhibition of viral gene expression was also noted, However, it was found that As2O3 at a high concentratio

  18. Arsenic Trioxide Induced Differentiation and Apoptosis in Human Nasopharyngeal Carcinoma Xenografts in BALB/C Nude Mice

    Institute of Scientific and Technical Information of China (English)

    ZHENGYuwu; DUCaiwen; LIDerui; LINYingcheng; WUMingyao

    2004-01-01

    To study the effect of arsenic trioxide (As2O3) on human poorly differentiated nasopharyngeal cancer cell line, CSNE-1, in vivo and its possible mechanism of action. Methods: CSNE-1 cells were established as xenografts in BALB/C nude mice. The tumor-bearing mice were treated with As2O3 at the dose of 5 mg/kg every day. The tumor growth was observed by tumor-growth curve. Morphologic changes were studied under light microscopy and electron microscopy. TUNEL was used to detect apoptosis. The expression of PCNA, p53, Bcl-2 and Bax were determined by immunohistochemistry. Results: The cell growth and proliferate activity were significantly inhibited by As203 at the dose of 5 mg/kg every day. Morphologic changes such as the formation of keratinization of tumor cells, decreased ratio of nuclear/cytoplasm, increased organelle and plasmic fibril in cytoplasm were identified. Cytodesma, desmosomes and micro-process were seen under light microscopy and transmission electron microscopy, which revealed that the cancer cells underwent differentiation. In addition, remarkable cell apoptosis were observed by TUNEL assay. Over expression of p53 and Bax was detected in the As203 treatment group when compared with control group. Conclusion: As203 inhibited proliferation of human poorly differentiated nasopharyngeal cancer cell CSNE-1 by inducing differentiation and apoptosis, which may be related to the up-regulation of p53 and Bax expression.

  19. Arsenic trioxide inhibits accelerated allograft rejection mediated by alloreactive CD8(+) memory T cells and prolongs allograft survival time.

    Science.gov (United States)

    Li, Chun; Guan, Tianjun; Gao, Chang; Lin, Yingying; Yan, Guoliang; Zhu, Maoshu; Lv, Chongshan; Xia, Junjie; Qi, Zhongquan

    2015-09-01

    CD8(+) memory T (Tm) cells are a significant barrier to transplant tolerance induction in alloantigen-primed recipients, and are insensitive to existing clinical immunosuppressants. Here, we studied the inhibition of CD8(+) Tm cells by arsenic trioxide (As2O3) for the first time. Alloantigen-primed CD8(+) Tm cells were transferred to T cell immunodeficient nude mice. The mice were subjected to heart allotransplantation, and treated with As2O3. The transplant survival time was determined, and the inhibitory effects of As2O3 on CD8(+) Tm cell-mediated immune rejection were assessed through serological studies and inspection of the transplanted heart and lymphoid organs. We found that As2O3 treatment prolonged the mean survival time of the graft and reduced the number of CD8(+) Tm cells in the spleen and lymph nodes. The expression of the genes encoding interleukin (IL)-2, and IFN-γ was reduced, while expression of IL-10 and transforming growth factor-β was increased in the transplant. Our findings show that As2O3 treatment inhibits allograft rejection mediated by alloreactive CD8(+) Tm cells in the mouse heart transplantation model.

  20. Salvianolic Acid B Prevents Arsenic Trioxide-Induced Cardiotoxicity In Vivo and Enhances Its Anticancer Activity In Vitro

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    Min Wang

    2013-01-01

    Full Text Available Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2 cells and human cervical cancer (HeLa cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects.

  1. Impact of Arsenic Trioxide on LS-174T Cell Growth in vitro and the Activity of Telomerase

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The therapeutic action of arsenic trioxide( As2O3 ) on solid tumors has aroused widespread interest among scholars. To study the impact of As2 O3 on human colorectal carcinoma cells( LS-174T cell) and the activity of telomerase,the methods of PCR-ELISA, flow cytometry (FCM) and MTT assay in vitro were utilized. The results show that ( 1 ) with an increase in the concentration of As2 O3, the ratio of living the cells to dead cells decreases significantly,and the IC50 value is 5. 23 μg/mL; (2) the cells of the experimental groups can endure a series of morphological changes similar to the features of apoptosis; (3) the apoptotic curves of FCM pictures appear after 24 h, and the cells show the apoptosis in a time-dependent manner; (4) As2O3 can inhibit the activity of telomerase of the cell extraction obviously in a concentration-dependent and time-dependent manner after 24 h. It can be concluded from the experiment results in vitro that As2O3 can induce the apoptosis of LS-174T cells and inhibit the telomerase activity. Therefore, it has been proposed, for the first time, that these two factors( the apoptosis of LS-174T cells and the inhibition to the telomerase activity) are important causes of the LS-174T cell death caused by As2O3.

  2. Sumoylation of the Tumor Suppressor Promyelocytic Leukemia Protein Regulates Arsenic Trioxide-Induced Collagen Synthesis in Osteoblasts

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    Wen-Xiao Xu

    2015-11-01

    Full Text Available Background/Aims: Promyelocytic leukemia (PML protein is a tumor suppressor that fuses with retinoic acid receptor-α (PML-RARα to contribute to the initiation of acute promyelocytic leukemia (APL. Arsenic trioxide (ATO upregulates expression of TGF-β1, promoting collagen synthesis in osteoblasts, and ATO binds directly to PML to induce oligomerization, sumoylation, and ubiquitination. However, how ATO upregulates TGF-β1 expression is uncertain. Thus, we suggested that PML sumoylation is responsible for regulation of TGF-β1 protein expression. Methods: Kunming mice were treated with ATO, and osteoblasts were counted under scanning electron microscopy. Masson's staining was used to quantify collagen content. hFOB1.19 cells were transfected with siRNA against UBC9 or RNF4, and then treated with ATO or FBS. TGF-β1, PML expression, and sumoylation were quantified with Western blot, and collagen quantified via immunocytochemistry. Results: ATO enhanced osteoblast accumulation, collagen synthesis, and PML-NB formation in vivo. Knocking down UBC9 in hFOB1.19 cells inhibited ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. Conversely, knocking down RNF4 enhanced ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. Conclusion: These data suggest that PML sumoylation is required for ATO-induced collagen synthesis in osteoblasts.

  3. Arsenic trioxide promotes senescence and regulates the balance of adipogenic and osteogenic differentiation in human mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Huanchen Cheng; Lin Qiu; Hao Zhang; Mei Cheng; Wei Li; Xuefei Zhao; Keyu Liu; Lei Lei; Jun Ma

    2011-01-01

    Arsenic trioxide (ATO) as an anti-tumor drug could induce differentiation and apoptosis in tumor cells.Mesenchymal stem cells (MSCs) play important roles in the hematogenesis of bone marrow. Many reports have shown that the disorder of MSC adipogenic and osteogenic differentiation occurs in some diseases. However,reports about the effects of ATO on MSCs are limited. In this study, we found that 1μM ATO promoted MSC senescence mainly through p21, although it had no effect on apoptosis at this dose. Furthermore, ATO promoted adipogenic differentiation, but inhibited osteogenic differentiation in MSCs. Our study also showed that CCAAT/enhancer-binding protein alpha C/EBPα and peroxisome proliferator-activated receptor gamma PPARγ might be involved in the regulation of adipogenic and osteogenic differentiation induced by ATO. Our results indicated that ATO may exert an anti-tumor effect by influencing bone marrow micro-environment. Moreover, it may regulate the adipogenic and osteogenic differentiation of MSCs.

  4. Melatonin enhances arsenic trioxide-induced cell death via sustained upregulation of Redd1 expression in breast cancer cells.

    Science.gov (United States)

    Yun, Sun-Mi; Woo, Sang Hyeok; Oh, Sang Taek; Hong, Sung-Eun; Choe, Tae-Boo; Ye, Sang-Kyu; Kim, Eun-Kyu; Seong, Min Ki; Kim, Hyun-A; Noh, Woo Chul; Lee, Jin Kyung; Jin, Hyeon-Ok; Lee, Yun-Han; Park, In-Chul

    2016-02-15

    Melatonin is implicated in various physiological functions, including anticancer activity. However, the mechanism(s) of its anticancer activity is not well understood. In the present study, we investigated the combined effects of melatonin and arsenic trioxide (ATO) on cell death in human breast cancer cells. Melatonin enhanced the ATO-induced apoptotic cell death via changes in the protein levels of Survivin, Bcl-2, and Bax, thus affecting cytochrome c release from the mitochondria to the cytosol. Interestingly, we found that the cell death induced by co-treatment with melatonin and ATO was mediated by sustained upregulation of Redd1, which was associated with increased production of reactive oxygen species (ROS). Combined treatment with melatonin and ATO induced the phosphorylation of JNK and p38 MAP kinase downstream from Redd1 expression. Rapamycin and S6K1 siRNA enhanced, while activation of mTORC1 by transfection with TSC2 siRNA suppressed the cell death induced by melatonin and ATO treatment. Taken together, our findings suggest that melatonin enhances ATO-induced apoptotic cell death via sustained upregulation of Redd1 expression and inhibition of mTORC1 upstream of the activation of the p38/JNK pathways in human breast cancer cells. PMID:26607805

  5. Effect of Arsenic Trioxide with Various Concentrations on Dendritic Cells in the Conducting Airways of Asthmatic Mice

    Institute of Scientific and Technical Information of China (English)

    YINKai-sheng; ZHOULin-fu; JIXiao-hui; LENGJing; YANGYu

    2004-01-01

    To investigate the effect of arsenic trioxide (As2O3 )with three different concentration groups on the distribution and recruitment of dendritic cells(DCs) in the conducting airways of asthmatic mice. Methods: Fifty BALB/c mice were divided into 5 groups at random: control group, asthmatic group, therapeutic groups with low dose(1 mg/kg), moderate dose( 5 mg/lqg) and high dose( 10 mg/kg) of As2O3. The immunohistochomistry, scanning electron microscope and computerized image analysis were applied to detect airway DCs, respectively. Results: We demonstrated from the control mice that all intraepithelial NLDC-145 DCs throughout the respiratory tree cotdd be accounted for a network of cells with dendritic cell morphology, and the density of DCs varied from(500±50) cells/ram2 epithelial surface in the large airways, to(60±10)cells/mm2 epithelial surface in the small airways(P0.05).Conchsion : Our findings suggest that it might be an important therapeutic mechanism of As2 03 to downregulate not the distribution but the density of DCs in the conducting airways of asthmatic mice,and low dose of As203 has potential value in treating asthma.

  6. 三氧化二砷的代谢途径及毒理机制综述%Toxicity Mechanisms and Metabolic Pathways of Arsenic Trioxide

    Institute of Scientific and Technical Information of China (English)

    牛一民; 樱井徹郎; 孙晖; 王喜军

    2011-01-01

    Arsenic trioxide is well known as a deadly poison. However, arsenous acid injection, which is originated from white arsenic in traditional Chinese medicine (TCM), has great efficacy in the treatment of acute promyeloeytic leukemia (APL). This medication is still accompanied with some severe adverse drug reactions (ADR). This paper tried to discuss metabolic pathways, as well as acute and chronic mechanisms of arsenic trioxide. The hypothetic ADB mechanism of arsenous acid injection was proposed to provide basis for new drug discovery in order to eliminate ADR.%三氧化二砷作为剧毒药广为人知,传统中药称其为"砒霜",而从中药砒霜中诞生的亚砷酸注射液其治疗急性早幼粒细胞白血病的疗效又为世人所瞩目,但仍伴随不同程度的不良反应.本文主要介绍了三氧化二砷的代谢途径及急慢性毒性机制,提出亚砷酸注射液不良反应的机制假设,为研究开发消除不良反应的药物提供依据.

  7. The effect of nilotinib plus arsenic trioxide on the proliferation and differentiation of primary leukemic cells from patients with chronic myoloid leukemia in blast crisis

    OpenAIRE

    Wang, Wei; Lv, Fei-fei; DU, YAN; Li, Nannan; Chen, Yaling; Chen, Lihong

    2015-01-01

    Aim To determine the effects of arsenic trioxide (ATO) and nilotinib (AMN107, Tasigna) alone or in combination on the proliferation and differentiation of primary leukemic cells from patients with chronic myeloid leukemia in the blast crisis phase (CML-BC). Methods Cells were isolated from the bone marrow of CML-BC patients and were treated with 1 μM ATO and 5 nM nilotinib, either alone or in combination. Cell proliferation was evaluated using a MTT assay. Cell morphology and the content of h...

  8. Comparative investigations of sodium arsenite, arsenic trioxide and cadmium sulphate in combination with gamma-radiation on apoptosis, micronuclei induction and DNA damage in a human lymphoblastoid cell line

    International Nuclear Information System (INIS)

    In the field of radiation protection the combined exposure to radiation and other toxic agents is recognised as an important research area. To elucidate the basic mechanisms of simultaneous exposure, the interaction of the carcinogens and environmental toxicants cadmium and two arsenic compounds, arsenite and arsenic trioxide, in combination with gamma-radiation in human lymphoblastoid cells (TK6) were investigated. Gamma-radiation induced significant genotoxic effects such as micronuclei formation, DNA damage and apoptosis, whereas arsenic and cadmium had no significant effect on these indicators of cellular damage at non-toxic concentrations. However, in combination with gamma-radiation arsenic trioxide induced a more than additive apoptotic rate compared to the sum of the single effects. Here, the level of apoptotic cells was increased, in a dose-dependent way, up to two-fold compared to the irradiated control cells. Arsenite did not induce a significant additive effect at any of the concentrations or radiation doses tested. On the other hand, arsenic trioxide was less effective than arsenite in the induction of DNA protein cross-links. These data indicate that the two arsenic compounds interact through different pathways in the cell. Cadmium sulphate, like arsenite, had no significant effect on apoptosis in combination with gamma-radiation at low concentrations and, at high concentrations, even reduced the radiation-induced apoptosis. An additive effect on micronuclei induction was observed with 1 μM cadmium sulphate with an increase of up to 80% compared to the irradiated control cells. Toxic concentrations of cadmium and arsenic trioxide seemed to reduce micronuclei induction. The results presented here indicate that relatively low concentrations of arsenic and cadmium, close to those occurring in nature, may interfere with radiation effects. Differences in action of the two arsenic compounds were identified

  9. Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell lines

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This study aimed to investigate the effects of arsenic trioxide(As2O3) on the mitochondrial DNA(mtDNA) of acute promyelocytic leukemia(APL) cells.The NB4 cell line was treated with 2.0 μmol/L As2O3 in vitro,and the primary APL cells were treated with 2.0 μmol/L As2O3 in vitro and 0.16 mg kg-1 d-1 As2O3 in vivo.The mitochondrial DNA of all the cells above was amplified by PCR,directly sequenced and analyzed by Sequence Navigatore and Factura software.The apoptosis rates were assayed by flow cytometry.Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As2O3 use,but the mutation spots were remarkably increased after As2O3 treatment,which was positively correlated to the rates of cellular apoptosis,the correlation coefficient:rNB4-As2O3=0.973818,and rAPL-As2O3=0.934703.The mutation types include transition,transversion,codon insertion or deletion,and the mutation spots in all samples were not constant and regular.It is revealed that As2O3 aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo.Mitochondrial DNA might be one of the targets of As2O3 in APL treatment.

  10. Study of electron spin resonance and viscosity for hemoglobin polymer after arsenic trioxide and gamma irradiation treatment

    Directory of Open Access Journals (Sweden)

    Aisha A. Saad-El-Din

    2014-10-01

    Full Text Available The present work aimed to study the intensity of electron spin resonance (ESR of hemoglobin rat's polymer and changes in rheological properties (viscosity. This study included five groups: control, irradiation with single dose of 5 Gy gamma irradiation, intraperitoneal injection with single dose of arsenic trioxide (As2O3 10 mg/kg body weight, As2O3 followed by 5 Gy and 5 Gy followed by As2O3. The results of ESR spectroscopy indicated that the intensity increases significantly for As2O3 and non-significantly with 5 Gy of gamma radiation compared with control, which indicated an increase in the number of free radicals. Injection with As2O3 after and before 5 Gy resulted in non-significant decrease which given rise to a decrease in the number of free radicals. there was significant decrease in viscosity for 5 Gy at different shear rates (11.3–375 sec−1, viscosity for As2O3 injection group showed non-significant decrease, and non-significant increase in case of 5 Gy followed by As2O3 injection, significant decrease at high shear rate in case of 5 Gy followed by As2O3. These results concluded that 5 Gy followed by As2O3 showed some sort of repair in the function of rats hemoglobin rather than injection with As2O3 and 5 Gy both individually.

  11. A drug from poison: how the therapeutic effect of arsenic trioxide on acute promyelocytic leukemia was discovered.

    Science.gov (United States)

    Rao, Yi; Li, Runhong; Zhang, Daqing

    2013-06-01

    It is surprising that, while arsenic trioxide (ATO) is now considered as "the single most active agent in patients with acute promyelocytic leukemia (APL)", the most important discoverer remains obscure and his original papers have not been cited by a single English paper. The discovery was made during the Cultural Revolution when most Chinese scientists and doctors struggled to survive. Beginning with recipes from a countryside practitioner that were vague in applicable diseases, Zhang TingDong and colleagues proposed in the 1970s that a single chemical in the recipe is most effective and that its target is APL. More than 20 years of work by Zhang and colleagues eliminated the confusions about whether and how ATO can be used effectively. Other researchers, first in China and then in the West, followed his lead. Retrospective analysis of data from his own group proved that APL was indeed the most sensitive target. Removal of a trace amount of mercury chloride from the recipe by another group in his hospital proved that only ATO was required. Publication of Western replication in 1998 made the therapy widely accepted, though neither Western, nor Chinese authors of English papers on ATO cited Zhang's papers in the 1970s. This article focuses on the early papers of Zhang, but also suggests it worth further work to validate Chinese reports of ATO treatment of other cancers, and infers that some findings published in Chinese journals are of considerable value to patients and that doctors from other countries can benefit from the clinical experience of Chinese doctors with the largest population of patients. PMID:23645104

  12. Regulating effects of arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats

    Institute of Scientific and Technical Information of China (English)

    XUE Dong-bo; ZHANG Wei-hui; YUN Xiao-guang; SONG Chun; ZHENG Biao; SHI Xing-ye; WANG Hai-yang

    2007-01-01

    Background It is accepted that inflammatory cytokines play a key role in the development of acute pancreatitis, so blocking the initiation of inflammatory reactions may alleviate pathological changes of acute pancreatitis. We studied the regulatory effect of arsenic trioxide (As2O3) on apoptosis and oncosis of pancreatic acinar cells in vitro and in vivo and its therapeutic effect on acute pancreatitis.Methods Pancreatic acinar cells were isolated by collagenase digestion method. Apoptosis and oncosis of isolated pancreatic acinar cells were detected with Hoechst 33258+PI or Annexin V+PI double fluorescent staining. Amylase and lactate dehydrogenase release were measured. Acute pancreatitis was induced in Wistar rats by intraperitoneal injections of caerulein, and apoptosis was detected with terminal dUTP nick-end labeling method. Tumor necorsis factor α (TNF-α) mRNA, myeloperoxidase, nuclear factor-κB and histological grading of pancreatic damage were measured.Results There was an increased apoptosis but a decreased oncosis of pancreatic acinar cell after the treatment with As2O3. The levels of lactate dehydrogenase and amylase release were markedly decreased in As2O3 treated group.Myeloperoxidase content, TNF-α mRNA level, nuclear factor-κB activation and pathological score in As2O3 treated group were significantly lower than in the untreated group.Conclusions As2O3 can induce apoptosis and reduce oncosis of pancreatic acinar cell, thus resulting in reduced release of endocellular enzyme of acinar cells, reduced inflammatory cell infiltration and decreased the production of inflammatory cytokines, so that the outcome of alleviated pathological changes was finally achieved.

  13. The present treatment and mechanism progress of arsenic trioxide in hematological malignancies

    Institute of Scientific and Technical Information of China (English)

    Lin Liu; Zhi-Gang Zhao

    2016-01-01

    Arsenic trioide (ATO) is a kind of highly toxic substances and the main effective components of arsenic. ATO has been used medicinally for over 2400 years. Recent years, many studies have found that ATO has a significant efficacy on the acute promyelocytic leukemia (APL). To further explore the latest findings of research on the treatment of hematologic malignanies of ATO, this paper reviewed the development history of ATO, and summarized its mechanisms and clinical application in the treatment of hematologic malignancies. In addition, we want to provide new ideas for researches on the treatment of cancer of ATO.%三氧化二砷(ATO)是一种剧毒物质,又是中药砒霜的主要成分,人类用它作为药物治疗疾病已有2400多年的历史。近年来发现ATO对急性早幼粒细胞性白血病(APL)具有显著的疗效。为进一步了解ATO治疗血液系统恶性肿瘤作用的研究近况,本文回顾ATO的研发历史,并总结其在治疗血液恶性肿瘤中的作用机制及临床应用,以期为ATO治疗肿瘤方面的研究提供新的思路。

  14. Relapsed APL patient with variant NPM-RARalpha fusion responded to arsenic trioxide-based therapy and achieved long-term survival.

    Science.gov (United States)

    Chen, Yan; Gu, Ling; Zhou, Chenyan; Wu, Xueqiang; Gao, Ju; Li, Qiang; Zhu, Yiping; Jia, Cangsong; Ma, Zhigui

    2010-05-01

    The t(5;17)/NPM-RARalpha is the second variant chromosomal translocation in acute promyelocytic leukemia (APL) to be characterized and also the second most plentiful variant translocation. So far, there is a lack of information on the effectiveness of arsenic trioxide (ATO) in relapsed APL with variant RARalpha chimera including t(5;17)/NPM-RARalpha. We report here a long-term survived APL patient with variant NPM-RARalpha fusion who relapsed four times and each time responded well to ATO or ATO-based re-induction therapy. The patient had received a total of more than 3,500 mg of ATO, but showed no obvious arsenic-related toxicities. This case illustrates the long-term efficiency and safety of ATO-based therapy not only in newly diagnosed APL, but also in relapsed APL including those with variant translocations.

  15. The current research of arsenic trioxide in the treatment of acute promyelocytic leukemia%三氧化二砷治疗急性早幼粒细胞白血病的研究现状

    Institute of Scientific and Technical Information of China (English)

    郭晶杰

    2013-01-01

    Arsenic trioxide( ATO )is presently one of the most effective single agent in the treatment of a-cute promyelocytic leukemia( APL ). ATO impressivly increases the complete remission rate and prolongs survival of patients with APL with only mild and transient adverse effects. The mechanisms of ATO mainly include promoting differentiation,inducing apoptosis,accumulating reactive oxygen species,and eliminating leukemic - initiating cells. And synergistic actions in introduction of apoptosis and differentiation between ATO and all - trans - retino-ic acid have been shown. In relapsed APL, ATO - based salvage therapy has been able to induce long - lasting remissions and possible cure in 50% -81% of patients. The high anti - leukemic efficacy and the favorable toxicity profile of ATO were also shown in newly diagnosed APL,because high remission and cure rates could even be induced by ATO alone. Experimental research and clinical studies have established ATO as an important candidate for the further improvement of APL therapy.%三氧化二砷(Arsenic trioxide,ATO)是目前单药治疗急性早幼粒细胞白血病(Acute promyelocytic leukemia,APL)最有效的药物之一,可明显提高APL的完全缓解率,延长患者的生存期,且不良反应较轻.ATO的作用机制主要为诱导APL细胞分化与凋亡、促使细胞内活性氧水平升高和去除白血病启动细胞等,并且在诱导分化和凋亡方面与全反式维甲酸起协同作用.对于复发性APL,以ATO为基础的挽救疗法能够诱导APL长期缓解并且50%~81%的患者可能治愈.在初发APL中,ATO表现出抗白血病的高效性和低毒性,使APL获得较高的缓解率和治愈率.因此,对ATO进行深入的基础及临床研究将为进一步优化ATO对APL的治疗提供重要的参考.

  16. Treatment of an acute promyelocytic leukemia relapse using arsenic trioxide and all-trans-retinoic in a 6-year-old child.

    Science.gov (United States)

    Rock, Nathalie; Mattiello, V; Judas, C; Huezo-Diaz, P; Bourquin, J P; Gumy-Pause, F; Ansari, M

    2014-03-01

    In adult therapy, arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) are recognized as active treatment of relapsed acute promyelocytic leukemia (APL). The efficacy of this combination in pediatric APL has not yet been well established. We report the case of a 6-year-old girl with relapsed APL, with a PML-RARα mutation, treated with a combination of ATO and ATRA. Over a period of 5 months, she received in total, 75 doses of intravenous ATO and 40 doses of oral ATRA. Currently, 22 months after relapse, she is still in complete remission. Here, we describe treatment of a relapsed APL in a child with limited treatment of ATO and ATRA and review the literature. PMID:24498972

  17. Anti-hepatoma effect of arsenic trioxide on experimental liver cancer induced by 2-acetamidofiuorene in rats

    Institute of Scientific and Technical Information of China (English)

    Bing Tan; Jie-Fei Huang; Qun Wei; Hong Zhang; Run-Zhou Ni

    2005-01-01

    AIM: To study the anti-hepatoma efficiency of arsenic trioxide (As2O3) in the treatment of experimental rat hepatocellular carcinoma (HCC) induced by 2-acetamidofluorene (2-FAA)and to elucidate the possible mechanisms.METHODS: SD rats (2 mo old) had been fed with 2-FAA for 8 wk to induce HCC, and then they were treated with As2O3 or matrine. On d 29, the rats were killed and the liver was weighed and liver tumors were counted. The histological changes of liver tissue were observed under microscope, and the cellular dynamic parameters were studied by flow cytometry. Immunohistochemistry (two-step method) was used to observe the expression of vascular endothelial growth factor (VEGF) and micro-vessel density (MVD) on consecutive sections. The pathological parameters were also analyzed, the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT),total bilirubin (TBi), and direct bilirubin (DBi).RESULTS: The number of liver tumors decreasedsignificantly in groups treated with As2O3, especially in medium-dose (1 mg/kg) group (t = 2.80, P<0.01). As2O3 caused HCC cell death via apoptosis; necrosis was seen and apoptosis was common when the dose was 1 mg/kg.Proliferation index decreased sharply in medium-dose (1 mg/kg) group (7.87±4.11 vs 24.46±6.49, t = 2087,P<0.01), but not in 0.2 mg/kg group. However, S-phase fraction decreased dramatically in both groups, it reached the bottom level only when the dose was 1 mg/kg compared with control (0.40±0.13 vs 3.01±0.51, t = 2.97, P<0.01),and it was obviously accompanied with accumulation of cells in G0/G± (G0/G1 restriction). The expressions of VEGF and MVD in medium-dose (1 mg/kg) group were significantly lower than normal saline group (0.63±0.74 vs 2.44±0.88, P<0.05; 15.75±3.99 vs47.44±13.41, t= 2.80,P<0.01). Compared with normal saline group, mediumand low-dose groups As2O3 and matrine lowered the levels of ALT in serum (61.46±9.46, 63.75±20.40, 61.18±13.00 vs 108.98±29.86, t= 2

  18. Arsenic trioxide suppresses liver X receptor β and enhances cholesteryl ester transfer protein expression without affecting the liver X receptor α in HepG2 cells.

    Science.gov (United States)

    Cheng, Tain-Junn; Lin, Shu-Wen; Chen, Chih-Wei; Guo, How-Ran; Wang, Ying-Jang

    2016-10-25

    Chronic arsenic exposure is associated with cerebrovascular disease and the formation of atherosclerotic lesions. Our previous study demonstrated that arsenic trioxide (ATO) exposure was associated with atherosclerotic lesion formation through alterations in lipid metabolism in the reverse cholesterol transport process. In mouse livers, the expression of the liver X receptor β (LXR-β) and the cholesteryl ester transfer protein (CETP) was suppressed without any changes to the lipid profile. The aim of this study was to elucidate whether ATO contributes to atherosclerotic lesions by suppressing LXR-β and CETP levels in hepatocytes. HepG2 cells, human hepatocytes, were exposed to different ATO concentrations in vitro. Cell viability was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. The liver X receptor α (LXR-α), LXR-β, sterol regulatory element-binding protein-1c (SREBP-1c) and CETP protein levels were measured by Western blotting, and their mRNA levels were measured by real-time PCR. Cholesterol efflux was analyzed by flow cytometry. The results showed ATO inhibited LXR-β mRNA and protein levels with a subsequent decrease in SREBP-1c protein levels and reduced cholesterol efflux from HepG2 cells into the extracellular space without influencing LXR-α mRNA and protein levels. CETP protein levels of HepG2 cells were significantly elevated under arsenic exposure. Transfection of LXR-β shRNA did not change CETP protein levels, implying that there is no cross-talk between LXR-β and CETP. In conclusion, arsenic not only inhibits LXR-β and SREBP-1c mRNA and protein levels but also independently increases CETP protein levels in HepG2 cells. PMID:27622732

  19. 三氧化二砷纳米粒子对直肠癌作用的实验研究%Study on anticancer effect of arsenic trioxide nanoparticles on rectal cancer

    Institute of Scientific and Technical Information of China (English)

    梁桃; 陈颖颖; 薄挽澜

    2010-01-01

    目的 探讨三氧化二砷纳米粒子在体外、体内对直肠癌的抗癌作用.方法 Annexin V-FITC/PI染色流式细胞术检测三氧化二砷纳米粒子诱导直肠癌细胞HR8348凋亡情况;建立HR8348细胞裸鼠皮下移植瘤模型,监测给药后肿瘤体积的变化,并通过对肿瘤组织标本Ki67染色和TUNEL染色检测肿瘤细胞增殖和凋亡情况.结果 流式细胞术结果显示,4.0 μmol/L三氧化二砷纳米粒子诱导直肠癌细胞凋亡率为7.02%,高于对照组(1.76%),P<0.05,三氧化二砷纳米粒子体外可诱导直肠癌细胞的凋亡.在体内,三氧化二砷纳米粒子可抑制HR8348裸鼠皮下移植瘤的生长,4.0 μmol/L三氧化二砷纳米粒子组增殖指数(31.61%)低于对照组(66.75%),而凋亡指数(19.21%)高于对照组(6.47%),P<0.05.可抑制肿瘤细胞的增殖,诱导细胞凋亡.结论 在直肠癌中,三氧化二砷纳米粒子通过抑制增殖,诱导凋亡而发挥抗癌作用,是直肠癌治疗的良好药物.%Objective To investigate the anticancer effect of arsenic trioxide nanoparticles on rectal cancer in vitro and in vivo. Methods In cultured rectal cancer cells HR8348, flow cytometry were used to evaluate proliferation inhibitory and proapoptotic effect of arsenic trioxide nanoparticles; Rectal cancer xenograft model was established by s.c. injection of HR8348 cells into nude mice. The tumor volume was monitored after exposure to arsenic trioxide nanoparticles, Ki67 staining and TUNEL assay were used to assess tumor cell proliferation and apoptosis in tumor tissue. Results The data of flow cytometry indicate that cancer cell apoptosis induced by 4.0 μmol/L arsenic trioxide nanoparticles was 7.02%, higher than by control group ( 1.76% ),P <0.05. In vivo, arsenic trioxide nanoparticles can inhibit the growth of HR8348 nude mice. In the group of 4. 0 μmol/L arsenic trioxide nanoparticles ,proliferation index (31.61%) was lower than in the control group (66.75%), while the

  20. Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells.

    Science.gov (United States)

    Martelli, Maria Paola; Gionfriddo, Ilaria; Mezzasoma, Federica; Milano, Francesca; Pierangeli, Sara; Mulas, Floriana; Pacini, Roberta; Tabarrini, Alessia; Pettirossi, Valentina; Rossi, Roberta; Vetro, Calogero; Brunetti, Lorenzo; Sportoletti, Paolo; Tiacci, Enrico; Di Raimondo, Francesco; Falini, Brunangelo

    2015-05-28

    Nucleophosmin (NPM1) mutations represent an attractive therapeutic target in acute myeloid leukemia (AML) because they are common (∼30% AML), stable, and behave as a founder genetic lesion. Oncoprotein targeting can be a successful strategy to treat AML, as proved in acute promyelocytic leukemia by treatment with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO), which degrade the promyelocytic leukemia (PML)-retinoic acid receptor fusion protein. Adjunct of ATRA to chemotherapy was reported to be beneficial for NPM1-mutated AML patients. Leukemic cells with NPM1 mutation also showed sensibility to ATO in vitro. Here, we explore the mechanisms underlying these observations and show that ATO/ATRA induce proteasome-dependent degradation of NPM1 leukemic protein and apoptosis in NPM1-mutated AML cell lines and primary patients' cells. We also show that PML intracellular distribution is altered in NPM1-mutated AML cells and reverted by arsenic through oxidative stress induction. Interestingly, similarly to what was described for PML, oxidative stress also mediates ATO-induced degradation of the NPM1 mutant oncoprotein. Strikingly, NPM1 mutant downregulation by ATO/ATRA was shown to potentiate response to the anthracyclin daunorubicin. These findings provide experimental evidence for further exploring ATO/ATRA in preclinical NPM1-mutated AML in vivo models and a rationale for exploiting these compounds in chemotherapeutic regimens in clinics. PMID:25795919

  1. A Hydrometallurgical Treatment of Arsenic-Bearing Intermediate Products in Smelters : Recovery of Valuable Metals and Arsenic Trioxide

    OpenAIRE

    戸沢, 一光; 梅津, 良昭; 西村, 忠久

    1980-01-01

    A hydrometallurgical treatment of speiss and some arsenic-bearing sulphide mixtures was tested. The principal steps of the process examined here are oxidative ammoniacal leaching, separation of arsenic as MgNH_4AsO_4・6H_2O from the leach solution, acid dissolution of the precipitate and the reduction of the arsenic to produce As_2O_3. The thermodynamic consideration and the leaching test with arsenic sulphide showed that oxidative ammoniacal leaching was applicable to arsenic sulphide and spe...

  2. Arsenic trioxide inhibits viability of pancreatic cancer stem cells in culture and in a xenograft model via binding to SHH-Gli

    Directory of Open Access Journals (Sweden)

    Han JB

    2013-08-01

    Full Text Available Jin-bin Han,1,2 Feng Sang,3 Jin-jia Chang,1,4 Yong-qiang Hua,1,2 Wei-dong Shi,1,2 Li-hua Tang,1,2 Lu-ming Liu1,2 1Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 3The Center for AIDS Research of the First Affiliated Hospital of Henan University of TCM, Zhengzhou, 4Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China Objective: Overexpression of the sonic hedgehog (SHH signaling pathway is an essential characteristic of pancreatic cancer stem cells (PCSCs and arsenic trioxide (ATO is described as a SHH inhibitor. This study evaluates whether ATO has the potential to inhibit viability of PCSCs via binding to SHH-Gli proteins. Methods: Cell counting kit-8 and flow cytometry were used for analyzing apoptosis in cells in vitro. The animal model was an athymic nude mouse model bearing subcutaneous xenografts of SW1990 pancreatic cancer cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry were used for tumor tissue analysis. The interaction between Gli1 and ATO was examined by a confocal system and an ultraviolet absorption spectrum assay. Results: ATO induced apoptosis in pancreatic cancer cells, especially CD24+CD44+ cells in vitro. Combination treatment of ATO and low dose gemcitabine inhibited tumor growth by 60.9% (P = 0.004, and decreased the expression of CD24, CD44, and aldehyde dehydrogenase 1 family, member A1 significantly in vivo. ATO changed the structure of the recombinant Gli1 zinc finger peptides in a cell-free condition and the binding action of ATO to recombinant Gli1 was observed in cultured pancreatic cancer cells. Conclusion: ATO may have the potential to inhibit viability of PCSCs via binding to SHH-Gli proteins in vitro and in vivo. Keywords: pancreatic cancer, stem cells, gemcitabine, arsenic trioxide, sonic

  3. Preparation of arsenic trioxide-loaded albuminutes immuno-nanospheres and its specific killing effect on bladder cancer cell in vitro

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jie; ZENG Fu-qing; LI Chong; TONG Qiang-song; GAO Xiang; XIE Shu-sheng; YU Li-zhang

    2005-01-01

    Background Recently, arsenic trioxide (As2O3) was considered as a novel anti-tumor agent. However, it showed severe toxicity effect on normal tissue at the same time. To improve its therapeutic efficacy and decrease its toxicity,we prepared arsenic trioxide-loaded albuminutes immuno-nanospheres [As2O3-(HAS-NS)-BDI-1] targeted with nonoclonal antibody (McAb) BDI-1 and tested its specific killing effect against bladder cancer cell. Methods As2O3-HAS-NS was prepared by chemical cross-linking method. Monoclonal antibody BDI-1 was purified with ammonium sulphate saltingout and chromatography. Albuminutes microspheres were conjugated with McAb by SPDP cross-linking method.Concentration of As in As2O3- (HAS-NS)-BDI-1 and As2O3-HAS-NS was measured by atomic fluometry method. As2O3- (HAS-NS)-BDI-1 and its activity were detected by SDS-PAGE reduction electrophoresis, indirect immunofluorescence test, light microscope and scanning electron microscope observation. Acridine orange staining and tritiated thymidine (3H-TdR) incorporation tests were used to indicate specific killing activity of As2O3-(HAS-NS)-BDI-1 in vitro. Results In As2O3- (HAS-NS)-BDI-1 groups, we saw two protein bands in SDS-PAGE reduction electrophoresis.Albuminutes immuno-nanospheres were rounded with clear green fluorescence by immunofluorescence test. Under microscope, we observed that BIU-87 cells were covered with the As2O3- (HAS-NS)-BDI-1 and that As2O3- (HAS-NS)-BDI-1 moved with the BIU-87 cells. The albuminutes immuno-nanospheres were tightly junctioned with the BIU-87 cells.Specific killing activity of As2O3-(HAS-NS)-BDI-1 on bladder tumor cells was observed by acridine orange staining and 3H-TdR incorporation assays. Conclusions As2O3- (HAS-NS)-BDI-1 might bind specifically against BIU-87 cells, thus leading to high activity of killing bladder tumor cells.

  4. Inorganic phosphate-triggered release of anti-cancer arsenic trioxide from a self-delivery system: an in vitro and in vivo study

    Science.gov (United States)

    Chen, Fei-Yan; Yi, Jing-Wei; Gu, Zhe-Jia; Tang, Bin-Bing; Li, Jian-Qi; Li, Li; Kulkarni, Padmakar; Liu, Li; Mason, Ralph P.; Tang, Qun

    2016-03-01

    On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced toxicity compared to the free drug. These results suggest a new drug delivery strategy which might be applied for ATO therapy on solid tumors.On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced

  5. The enhancement of sensitivity of HL-60 cells to arsenic trioxide by Bcl-2 siRNA%以Bcl-2为靶标siRNA提高HL-60细胞对三氧化二砷敏感性的探讨

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To study whether the small-interference RNA (siRNA) targeting against Bcl-2 gene can enhance sensitivity of HL-60 cell to arsenic trioxide. Methods: SiRNA was transferred into the HL-60 cells. At 6 h after transfection, the cells were cultured with arsenic trioxide. The cell growth of the HL-60 cells was detected using MTT at 24, 48 and 72 h, respectively.The levels of the Bcl-2 protein and reactive oxygen species (ROS), as well as of the membrane potential of the mitochondrion were determined by flow cytometry. Results: The Bcl-2 siRNA significantly increased the inhibitory action of arsenic trioxide on growth of HL-60 cells. The combination of siRNA with arsenic trioxide resulted in decrease of the Bcl-2 protein level and increase of the ROS level, as well as significant descending of the membrane potential of mitochondrion of HL-60 (P < 0.05).Conclusion: The siRNAtargeting Bcl-2 can increase the sensitivity of the HL-60 leukemia cells to arsenic trioxide by inhibiting the expression of Bcl-2 protein.

  6. Aquaporin 9, a promising predictor for the cytocidal effects of arsenic trioxide in acute promyelocytic leukemia cell lines and primary blasts.

    Science.gov (United States)

    Iriyama, Noriyoshi; Yuan, Bo; Yoshino, Yuta; Hatta, Yoshihiro; Horikoshi, Akira; Aizawa, Shin; Takeuchi, Jin; Toyoda, Hiroo

    2013-06-01

    A close correlation between the cytocidal effects of arsenic trioxide (ATO) and aquaporin-9 (AQP9) expression levels has been proposed, yet detailed studies are still needed to confirm this association. Thus, in the present study, the correlation between the expression levels of AQP9 and sensitivity to ATO was investigated using two acute promyelocytic leukemia (APL) cell lines, NB4 and HT93A, as well as primary APL cells from newly diagnosed and relapsed APL patients. A substantially higher sensitivity to ATO-mediated induction of apoptosis was observed in the NB4 cells when compared to that in the HT93A cells. In addition, markedly higher expression levels of AQP9, as assessed using flow cytometry, along with more intracellular arsenic accumulation, were observed in the NB4 cells. More importantly, similar to APL cell lines, the trend of expression levels of AQP9 correlated closely with the differential sensitivity to ATO-mediated induction of apoptosis in primary APL cells. In contrast, no correlation was observed between ATO sensitivity associated with AQP9 expression levels and the expression profiles of cell surface markers as well as chromosomal alterations. These results provide direct evidence that the expression levels of AQP9, rather than other biomarkers such as cell surface markers and chromosomal alterations, correlate closely with the sensitivity to ATO in both APL cell lines and primary blasts. These findings suggest that the AQP9 expression status of APL patients is a predictive marker for the successful outcome of ATO treatment, since AQP9 plays a pivotal role in various arsenite-mediated biological effects on normal and cancer cells. Moreover, flow cytometry may be a new convenient and valuable tool for analyzing the AQP9 status of APL patients compared to current methods such as western blotting.

  7. (+)α-Tocopheryl succinate inhibits the mitochondrial respiratory chain complex I and is as effective as arsenic trioxide or ATRA against acute promyelocytic leukemia in vivo.

    Science.gov (United States)

    dos Santos, G A S; Abreu e Lima, R S; Pestana, C R; Lima, A S G; Scheucher, P S; Thomé, C H; Gimenes-Teixeira, H L; Santana-Lemos, B A A; Lucena-Araujo, A R; Rodrigues, F P; Nasr, R; Uyemura, S A; Falcão, R P; de Thé, H; Pandolfi, P P; Curti, C; Rego, E M

    2012-03-01

    The vitamin E derivative (+)α-tocopheryl succinate (α-TOS) exerts pro-apoptotic effects in a wide range of tumors and is well tolerated by normal tissues. Previous studies point to a mitochondrial involvement in the action mechanism; however, the early steps have not been fully elucidated. In a model of acute promyelocytic leukemia (APL) derived from hCG-PML-RARα transgenic mice, we demonstrated that α-TOS is as effective as arsenic trioxide or all-trans retinoic acid, the current gold standards of therapy. We also demonstrated that α-TOS induces an early dissipation of the mitochondrial membrane potential in APL cells and studies with isolated mitochondria revealed that this action may result from the inhibition of mitochondrial respiratory chain complex I. Moreover, α-TOS promoted accumulation of reactive oxygen species hours before mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo antileukemic action and a novel mitochondrial target were revealed for α-TOS, as well as mitochondrial respiratory complex I was highlighted as potential target for anticancer therapy. PMID:21869839

  8. Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): prognostic significance of FLT3 mutations and complex karyotype.

    Science.gov (United States)

    Poiré, Xavier; Moser, Barry K; Gallagher, Robert E; Laumann, Kristina; Bloomfield, Clara D; Powell, Bayard L; Koval, Gregory; Gulati, Kabir; Holowka, Nicholas; Larson, Richard A; Tallman, Martin S; Appelbaum, Frederick R; Sher, Dorie; Willman, Cheryl; Paietta, Elisabeth; Stock, Wendy

    2014-07-01

    The addition of arsenic trioxide (ATO) to frontline therapy of acute promyelocytic leukemia (APL) has been shown to result in significant improvements in disease-free survival (DFS). FLT3 mutations are frequently observed in APL, but its prognostic significance remains unclear. We analyzed 245 newly diagnosed adult patients with APL treated on intergroup trial C9710 and evaluated previously defined biological and prognostic factors and their relationship to FLT3 mutations and to additional karyotypic abnormalities. FLT3 mutations were found in 48% of patients, including 31% with an internal tandem duplication (FLT3-ITD), 14% with a point mutation (FLT3-D835) and 2% with both mutations. The FLT3-ITD mutant level was uniformly low, < 0.5. Neither FLT3 mutation had an impact on remission rate, induction death rate, DFS or overall survival (OS). The addition of ATO consolidation improved outcomes regardless of FLT3 mutation type or level, initial white blood cell count, PML-RARA isoform type or transcript level. The presence of a complex karyotype was strongly associated with an inferior OS independently of post-remission treatment. In conclusion, the addition of ATO to frontline therapy overcomes the impact of previously described adverse prognostic factors including FLT3 mutations. However, complex karyotype is strongly associated with an inferior OS despite ATO therapy. PMID:24160850

  9. Arsenic Trioxide Induces Apoptosis and Incapacitates Proliferation and Invasive Properties of U87MG Glioblastoma Cells through a Possible NF-κB-Mediated Mechanism.

    Science.gov (United States)

    Ghaffari, Seyed H; Yousefi, Meysam; Dizaji, Majid Zaki; Momeny, Majid; Bashash, Davood; Zekri, Ali; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir

    2016-01-01

    Identification of novel therapeutics in glioblastoma remains crucial due to the devastating and infiltrative capacity of this malignancy. The current study was aimed to appraise effect of arsenic trioxide (ATO) in U87MG cells. The results demonstrated that ATO induced apoptosis and impeded proliferation of U87MG cells in a dosedependent manner and also inhibited classical NF-κB signaling pathway. ATO further upregulated expression of Bax as an important proapoptotic target of NF-κB and also inhibited mRNA expression of survivin, c-Myc and hTERT and suppressed telomerase activity. Moreover, ATO significantly increased adhesion of U87MG cells and also diminished transcription of NF-κB down-stream targets involved in cell migration and invasion, including cathepsin B, uPA, MMP-2, MMP-9 and MMP-14 and suppressed proteolytic activity of cathepsin B, MMP-2 and MMP-9, demonstrating a possible mechanism of ATO effect on a well-known signaling in glioblastoma dissemination. Taken together, here we suggest that ATO inhibits survival and invasion of U87MG cells possibly through NF-κB-mediated inhibition of survivin and telomerase activity and NF-κB-dependent suppression of cathepsin B, MMP-2 and MMP-9. PMID:27039805

  10. Nano-encapsulation of arsenic trioxide enhances efficacy against murine lymphoma model while minimizing its impact on ovarian reserve in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Richard W Ahn

    Full Text Available Advances in cancer therapy have increased the rate of survival of young cancer patients; however, female lymphoma patients frequently face a temporary or permanent loss of fertility when treated with traditional cytotoxic agents. The potential loss of fertility is an important concern that can influence treatment decisions for many premenopausal cancer patients. The negative effect of chemotherapeutic agents and treatment protocols to patients' fertility-referred to as fertotoxicity-are thus an increasingly important cancer survivorship issue. We have developed a novel nanoscale formulation of arsenic trioxide, a potent drug for treatment of hematological malignancies, and demonstrate that it has significantly better activity in a murine lymphoma model than the free drug. In parallel, we have developed a novel in vitro assay of ovarian follicle function that predicts in vivo ovarian toxicity of therapeutic agents. Our results reveal that the nanotherapeutic agent is not only more active against lymphoma, but is fertoprotective, i.e., it is much less deleterious to ovarian function than the parent drug. Thus, our in vitro assay allows rapid evaluation of both established and experimental anticancer drugs on ovarian reserve and can inform the selection of efficacious and fertility-sparing treatment regimens for reproductive-age women diagnosed with cancer.

  11. Inactivation of Akt by arsenic trioxide induces cell death via mitochondrial-mediated apoptotic signaling in SGC-7901 human gastric cancer cells.

    Science.gov (United States)

    Gao, Yan-Hui; Zhang, Hao-Peng; Yang, Shu-Meng; Yang, Yue; Ma, Yu-Yan; Zhang, Xin-Yu; Yang, Yan-Mei

    2014-04-01

    Arsenic trioxide (As2O3) has been recognized as a potential chemotherapeutic agent, yet the details concerning its mechanism of action in solid cancers remain undetermined. The present study assessed the role of Akt in the cell death induced by As2O3. The MTT assay showed that As2O3 suppressed the proliferation of SGC-7901 cells in a dose- and time-dependent manner. Characteristic apoptotic changes were observed in the As2O3‑treated cells by Hoechst 33342 staining, and FACS analysis showed that As2O3 caused dose-dependent apoptotic cell death. As2O3 activated caspase-3 and -9, and PARP cleavage in a dose-dependent manner. Compromised mitochondrial membrane potential and an increased protein level of Bax indicated involvement of mitochondia. As2O3 decreased the levels of p-Akt (Ser473), p-Akt (Thr308) and p-GSK-3β (Ser9), suggesting that As2O3 inactivated Akt kinase. In addition, LY294002 (a PI3 kinase inhibitor) augmented the apoptosis induced by As2O3. These results demonstrated that inhibition of PI3K/Akt signaling was involved in As2O3-induced apoptosis of gastric cancer SGC-7901 cells. PMID:24482137

  12. Indomethacin-Enhanced Anticancer Effect of Arsenic Trioxide in A549 Cell Line: Involvement of Apoptosis and Phospho-ERK and p38 MAPK Pathways

    Directory of Open Access Journals (Sweden)

    Ali Mandegary

    2013-01-01

    Full Text Available Background. Focusing on novel drug combinations that target different pathways especially apoptosis and MAPK could be a rationale for combination therapy in successful treatment of lung cancer. Concurrent use of cyclooxygenase (COX inhibitors with arsenic trioxide (ATO might be a possible treatment option. Methods. Cytotoxicity of ATO, dexamethasone (Dex, celecoxib (Cel, and Indomethacin (Indo individually or in combination was determined at 24, 48, and 72 hrs in A549 lung cancer cells. The COX-2 gene and protein expression, MAPK pathway proteins, and caspase-3 activity were studied for the most cytotoxic combinations. Results. The IC50s of ATO and Indo were 68.7 μmol/L and 396.5 μmol/L, respectively. Treatment of cells with combinations of clinically relevant concentrations of ATO and Indo resulted in greater growth inhibition and apoptosis induction than did either agent alone. Caspase-3 activity was considerably high in the presence of ATO and Indo but showed no difference in single or combination use. Phosphorylation of p38 and ERK1/2 was remarkable in the concurrent presence of both drugs. Conclusions. Combination therapy with ATO and Indo exerted a very potent in vitro cytotoxic effect against A549 lung cancer cells. Activation of ERK and p38 pathways might be the mechanism of higher cytotoxic effect of ATO-Indo combination.

  13. Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Choe, Tae-Boo [Department of Microbiological Engineering, Kon-Kuk University, Gwangjin-gu, Seoul (Korea, Republic of); Hong, Seok-Il [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Yi, Jae-Youn [Laboratory of Modulation of Radiobiological Responses, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Lee, Hyun-Gyu [Department of Microbiology and Immunology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Lee, Yun-Han, E-mail: yhlee87@yuhs.ac [Department of Radiation Oncology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Park, In-Chul, E-mail: parkic@kcch.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of)

    2014-07-11

    Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

  14. Effect of arsenic trioxide on vascular endothelial cell proliferation and expression of vascular endothelial growth factor receptors Flt-1 and KDR in gastric cancer in nude mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1) and VEGFR-2 (KDR) in human gastric tumor cells and proliferation of vascular endothelial cells.METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were treated with As2O3. Microvessel density (MVD) and expression of Flt-1 and KDR were detected by immunofluorescence laser confocal microscopy.SGC-7901 cells were treated respectively by exogenous recombinant human VEGF165 or VEGF165 + As2O3. Cell viability was measured by MTT assay. Cell viability of ECV304 cells was measured by MTT assay, and cell cycle and apoptosis were analyzed using flow cytometry.RESULTS: The tumor growth inhibition was 30.33% and 50.85%, respectively, in mice treated with As2O3 2.5 and 5 mg/kg. MVD was significantly lower in arsenic-treated mice than in the control group. The fluorescence intensity levels of Flt-1 and KDR were significantly less in the arsenic-treated mice than in the control group. VEGF165 may accelerate growth of SGC7901 cells, but As2O3 may disturb the stimulating effect of VEGF165. ECV304 cell growth was suppressed by 76.51%, 71.09% and 61.49% after 48 h treatment with As2O3 at 0.5, 2.5 and 5 μmol/L, respectively. Early apoptosis in the As2O3-treated mice was 2.88-5.1 times higher than that in the controls, and late apoptosis was 1.17-1.67 times higher than that in the controls.CONCLUSION: Our results showed that As2O3 delays tumor growth, inhibits MVD, down-regulates Flt-1 and KDR expression, and disturbs the stimulating effect of VEGF165 on the growth of SGC7901 cells. These results suggest that As2O3 might delay growth of gastric tumors through inhibiting the paracrine and autocrine pathways of VEGF/VEGFRs.

  15. Anti-tumor effect of arsenic trioxide on subcutaneously implanted Lewis lung carcinoma in mice%三氧化二砷对小鼠皮下移植性肺癌抑制及其机制的探讨

    Institute of Scientific and Technical Information of China (English)

    宋玉华; 彭鹏; 王清波; 邱少敏

    2012-01-01

    To evaluate the anti-angiogenesis effects of arsenic trioxide on transplanted lung carcinoma in mice. METHODS: Lewis lung carcinoma cells (LLC cells) were transplanted subcutaneously to C57BL/6 mice to generate tumors. Sixty mice were randomly divided into 3 groups (n = 20):negative control group,positive control group and arsenic trioxide treatment group. The tumor weight of the mice was measured respectively during the therapy. The tumor growth inhibition rates of each group were calculated. The expressions of VEGF and EGFR in the lung cancer tissue were examined by immunohistochemical method. RESULTS:The tumor weight of arsenic trioxide treatment group, positive control group and negative control group were (1 420±60),(l 500±80) and (2 420 ± 190) mg respectively. Compared with negative control group,the tumor weight of arsenic trioxide treatment group and positive control group were significantly lower than that of the negative control group (P0. 05). The expression of VEGF (63. 10 ± 5. 32)% and EGFR (68. 33 ±5. 99)% in arsenic trioxide treatment group were significantly less than those in negative control group [(76. 33 ± 10. 3)%,(80. 50±10. 21)%,P<0. 05]. CONCLUSION: Arsenic trioxide has strong inhibition effect on tumor growth;This effect was probably mediated by downregulating the expression of VEGF and EGFR.%目的:探讨三氧化二砷(AS2O3)对小鼠肺癌移植瘤的抑制作用,进一步分析其抗血管生成的可能机制.方法:建立Lewis肺癌小鼠移植瘤模型,60只小鼠随机分成阴性对照组、阳性对照组和AS2O3治疗组3组(每组20只),应用AS2O3治疗后,观察肿瘤生长情况计算抑瘤率,免疫组化法检测肿瘤组织内血管内皮生长因子(VEGF)和表皮生长因子受体(EGFR)的表达.结果:AS2O3组、阳性对照组、阴性对照组的瘤质量分别为(1 420±60)、(1 500±80)和(2 420±190) mg;AS2O3组和阳性对照组的瘤质量较阴性对照组明显减轻,P<0.05;AS2O3组的抑瘤率(52

  16. Clinical Study of Transarterial Chemoembolization for Primary Hepatic Carcinoma with Lipiodol-arsenic Trioxide Emulsion%亚砷酸-碘油乳剂经动脉栓塞治疗原发性肝癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    周玉斌; 吴丹明; 柳青峰

    2009-01-01

    Objective To evaluate the effect and toxicity of lipiodol-arsenic trioxide emulsion on the treatment of primary hepatic carcinoma. Methods Arsenic trioxide 20mg and lipiodol were fully mixtured into lipiodol-arsenic trioxide emulsion,which were injected into hepatic artery by catheters in 58 patients with primary hepatic carcinoma. If the patients' conditions progressed(tumor got larger or AFP increased),Anthracyctine would be used simultaneously. The effect and toxicity were observed. Results After 1~3 times of thera-py only with lipiodol-arsenic trioxide emulsion in all of 58 patients,objective response rate was 20.7% with 12 eases of PR,36 cases of NC and 10 cases of PD. AFP decreased from(11109.36±2920.82) IU/mL to(10001.61±2880.67) IU/mL averagely(P>0.05). An-thracycline was applied in 22 patients,and tumors got smaller in 16 cases after that. AFP decreased from (13901.11±4862.26) IU/mL to(5470.63±2597.79) IU/mL averagely(P0.05.22例患者在治疗中加用蒽环类药物,16例病灶有不同程度的缩小,AFP平均由(13901.11±4862.26)IU/mL降至(5470.63±2597.79)IU/mL,P<0.05.主要毒副反应为发热、恶心呕吐、肝区疼痛、血细胞减少及转氨酶升高等,全组未见不可逆毒副反应.结论 经肝动脉途径应用亚砷酸一碘油乳剂栓塞治疗原发性肝癌疗效较好,毒副反应较小,是一种较理想的微创治疗原发性肝癌的方法.

  17. Arsenic trioxide overcomes rapamycin-induced feedback activation of AKT and ERK signaling to enhance the anti-tumor effects in breast cancer.

    Directory of Open Access Journals (Sweden)

    Cynthia Guilbert

    Full Text Available Inhibitors of the mammalian target of rapamycin (mTORi have clinical activity; however, the benefits of mTOR inhibition by rapamycin and rapamycin-derivatives (rapalogs may be limited by a feedback mechanism that results in AKT activation. Increased AKT activity resulting from mTOR inhibition can be a result of increased signaling via the mTOR complex, TORC2. Previously, we published that arsenic trioxide (ATO inhibits AKT activity and in some cases, decreases AKT protein expression. Therefore, we propose that combining ATO and rapamycin may circumvent the AKT feedback loop and increase the anti-tumor effects. Using a panel of breast cancer cell lines, we find that ATO, at clinically-achievable doses, can enhance the inhibitory activity of the mTORi temsirolimus. In all cell lines, temsirolimus treatment resulted in AKT activation, which was decreased by concomitant ATO treatment only in those cell lines where ATO enhanced growth inhibition. Treatment with rapalog also results in activated ERK signaling, which is decreased with ATO co-treatment in all cell lines tested. We next tested the toxicity and efficacy of rapamycin plus ATO combination therapy in a MDA-MB-468 breast cancer xenograft model. The drug combination was well-tolerated, and rapamycin did not increase ATO-induced liver enzyme levels. In addition, combination of these drugs was significantly more effective at inhibiting tumor growth compared to individual drug treatments, which corresponded with diminished phospho-Akt and phospho-ERK levels when compared with rapamycin-treated tumors. Therefore, we propose that combining ATO and mTORi may overcome the feedback loop by decreasing activation of the MAPK and AKT signaling pathways.

  18. Anti-tumor Effect and Potential Mechanism of Arsenic Trioxide on SMMC-7721 Cells of Human Liver Cancer in Vivo and Vitro

    Institute of Scientific and Technical Information of China (English)

    Shen Bo

    2014-01-01

    Objective:To observe the anti-tumor effect of arsenic trioxide (As2O3) on SMMC-7721 cells of patients with liver cancer in vivo and vitro. Methods: Methyl Thiazolyl Tetrazolium (MTT) method, fluorescence microscope, FITC-AnnexinⅤ/PI double-tagging method and colorimetry were used to detect the survival rate, morphological change, apoptosis and Caspase-3 activity change of SMMC-7721 cells in different concentration of As2O3 for 48 h, respectively. As2O3 was injected into the transplanted tumors in nude mice with SMMC-7721 hepatoma cells to observe the growth of tumors. The mice were sacriifced after 12 d, followed by the extirpation and weighing of the tumors. Then Bcl-2, Bax and Caspase-3 expression were detected by immunohistochemistry. Results: As2O3 could obviously inhabit the proliferation of SMMC-7721 cells, with inhibition concentration (IC) being (18.17±2.10) μmol/L. Microscope showed typical morphological change of cell apoptosis and As2O3 treatment group was evidently higher than control group in apoptosis rate of SMMC-772 cells, suggesting that As2O3 could improve SMMC-772 cell activity. Internal injection of As2O3 into transplanted tumors in nude mice with SMMC-7721 hepatocellular lines could remarkably inhabit the growth of tumors with inhabiting rate being 52.37%, and immunohistochemistry also revealed that As2O3 could apparently up-regulate cell apoptosis-related Bax and Caspase-3 expression, and down-regulate Bcl-2 expression. Conclusion: As2O3 can inhabit the growth and in vivo oncogenesis of hepatoma SMMC-7721 cells, and induce SMMC-7721 cell apoptosis.

  19. Comparison of optical and power Doppler ultrasound imaging for non-invasive evaluation of arsenic trioxide as a vascular disrupting agent in tumors.

    Directory of Open Access Journals (Sweden)

    Mustafa K Alhasan

    Full Text Available Small animal imaging provides diverse methods for evaluating tumor growth and acute response to therapy. This study compared the utility of non-invasive optical and ultrasound imaging to monitor growth of three diverse human tumor xenografts (brain U87-luc-mCherry, mammary MCF7-luc-mCherry, and prostate PC3-luc growing in nude mice. Bioluminescence imaging (BLI, fluorescence imaging (FLI, and Power Doppler ultrasound (PD US were then applied to examine acute vascular disruption following administration of arsenic trioxide (ATO.During initial tumor growth, strong correlations were found between manual caliper measured tumor volume and FLI intensity, BLI intensity following luciferin injection, and traditional B-mode US. Administration of ATO to established U87 tumors caused significant vascular shutdown within 2 hrs at all doses in the range 5 to 10 mg/kg in a dose dependant manner, as revealed by depressed bioluminescent light emission. At lower doses substantial recovery was seen within 4 hrs. At 8 mg/kg there was >85% reduction in tumor vascular perfusion, which remained depressed after 6 hrs, but showed some recovery after 24 hrs. Similar response was observed in MCF7 and PC3 tumors. Dynamic BLI and PD US each showed similar duration and percent reductions in tumor blood flow, but FLI showed no significant changes during the first 24 hrs.The results provide further evidence for comparable utility of optical and ultrasound imaging for monitoring tumor growth, More specifically, they confirm the utility of BLI and ultrasound imaging as facile assays of the vascular disruption in solid tumors based on ATO as a model agent.

  20. Redox status of thioredoxin-1 (TRX1) determines the sensitivity of human liver carcinoma cells (HepG2) to arsenic trioxide-induced cell death

    Institute of Scientific and Technical Information of China (English)

    Changhai Tian; Ping Gao; Yanhua Zheng; Wen Yue; Xiaohui Wang; Haijing Jin; Quan Chen

    2008-01-01

    Intracellular redox homeostasis plays a critical role in determining tumor cells' sensitivity to drug-induced apop-tosis. Here we investigated the role of thioredoxin-1 (TRX1), a key component of redox regulation, in arsenic trioxide (As2O3)-induced apoptosis. Over-expression of wild-type TRX1 in HepG2 cells led to the inhibition of As2O3-induced cytochrome c (cyto c) release, caspase activation and apoptosis, and down-regulation of TRX1 expression by RNAi sensitized HepG, cells to As2O3-induced apoptosis. Interestingly, mutation of the active site of TRX1 from Cys32/35 to Ser32/35 converted this molecule from an apoptotic protector to an apoptotic promoter. In an effort to understand the mechanisms of this conversion, we used isolated mitochondria from mouse liver and found that recombinant wild-type TRX1 could protect mitochondria from the apoptotic changes. In contrast, the mutant form of TRX1 alone elicited mitochondria-related apoptotic changes, including the mitochondrial permeability transition pore (mPTP) opening, loss of mitochondrial membrane potential, and cyto c release from mitochondria. These apoptotic effects were inhibited by cyclosporine A (CsA), indicating that mutant TRX1 targeted to mPTP. Alteration of TRX1 from its reduced form to oxidized form in vivo by 2,4-dinitrochlorobenzene (DNCB), a specific inhibitor of TRX reductase, also sensitized HepG2 cells to As2O3-induced apoptosis. These data suggest that TRX1 plays a central role in regulating apoptosis by blocking cyto c release, and inactivation of TRX1 by either mutation or oxidization of the active site cysteines may sensitize tumor cells to As2O3-induced apoptosis.

  1. All-Trans Retinoic Acid plus Arsenic Trioxide versus All-Trans Retinoic Acid plus Chemotherapy for Newly Diagnosed Acute Promyelocytic Leukemia: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yafang Ma

    Full Text Available Recently, the all-trans retinoic acid (ATRA plus arsenic trioxide (ATO protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL, but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL.We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity.Overall, three studies were eligible for inclusion in this meta-analysis, which included a total of 585 patients, with 317 in ATRA plus ATO group and 268 in ATRA plus chemotherapy group. Compared with patients who received ATRA and chemotherapy, patients who received ATRA plus ATO had a significantly better event-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.22-0.67, p = 0.009, overall survival (HR = 0.44, 95% CI: 0.24-0.82, p = 0.009, complete remission rate (relative risk [RR] = 1.05; 95% CI: 1.01-1.10; p = 0.03. There were no significant differences in early mortality (RR = 0.48; 95% CI: 0.22-1.05; p = 0.07.Thus, this analysis indicated that ATRA plus ATO protocol may be preferred to standard ATRA plus chemotherapy protocol, particularly in low-to-intermediate risk APL patients. Further larger trials were needed to provide more evidence in high-risk APL patients.

  2. Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity.

    Science.gov (United States)

    Vineetha, Vadavanath Prabhakaran; Girija, Seetharaman; Soumya, Rema Sreenivasan; Raghu, Kozhiparambil Gopalan

    2014-03-01

    Evidences suggest that apple peel has a wide range of polyphenols having antioxidant activity and its consumption has been linked with improved health benefits. Arsenic trioxide (ATO) is a very effective drug for the treatment of acute promyelocytic leukemia (APL) but it leads to cardiotoxicity mediated through alterations in various cardiac ion channels and by increasing the intracellular calcium level and reactive oxygen species (ROS). The aim of the present investigation was to study the effect of methanolic extract of apple peel (APME) and aqueous extract of apple peel (APAE) on ATO (5 μM) induced toxicity in the H9c2 cardiac myoblast cell line. We estimated the cellular status of innate antioxidant enzymes, level of ROS, mitochondrial superoxide, glutathione and intracellular calcium with ATO and apple peel extracts. Prior to the cell line based study, we had evaluated the antioxidant potential of apple peel extract by 1,1-diphenyl-2-picrylhydrazyl (DPPH), total reducing power (TRP), superoxide anion and hydroxyl radical scavenging activity, in addition to quantifying total phenolic and flavonoid content. Both the extracts showed considerable antioxidant activity in cell-free chemical assays. In addition, both APME and APAE prevented the alteration in antioxidant status induced by ATO in H9c2 cells. Significant differential alterations had been observed in the activity of lactate dehydrogenase, superoxide dismutase, catalase, glutathione, glutathione peroxidase, thioredoxin reductase, xanthine oxidase, calcium overload and caspase 3 activity with ATO. The overall result revealed the protective property of polyphenol-rich apple peel extract against ATO induced cardiac toxicity via its antioxidant activity.

  3. TG-interacting factor transcriptionally induced by AKT/FOXO3A is a negative regulator that antagonizes arsenic trioxide-induced cancer cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zi-Miao; Tseng, Hong-Yu; Cheng, Ya-Ling [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Yeh, Bi-Wen [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Wu, Wen-Jeng [Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Huang, Huei-Sheng, E-mail: huanghs@mail.ncku.edu.tw [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China)

    2015-05-15

    Arsenic trioxide (ATO) is a multi-target drug approved by the Food and Drug Administration as the first-line chemotherapeutic agent for the treatment of acute promyelocytic leukemia. In addition, several clinical trials are being conducted with arsenic-based drugs for the treatment of other hematological malignancies and solid tumors. However, ATO's modest clinical efficacy on some cancers, and potential toxic effects on humans have been reported. Determining how best to reduce these adverse effects while increasing its therapeutic efficacy is obviously a critical issue. Previously, we demonstrated that the JNK-induced complex formation of phosphorylated c-Jun and TG-interacting factor (TGIF) antagonizes ERK-induced cyclin-dependent kinase inhibitor CDKN1A (p21{sup WAF1/CIP1}) expression and resultant apoptosis in response to ATO in A431 cells. Surprisingly, at low-concentrations (0.1–0.2 μM), ATO increased cellular proliferation, migration and invasion, involving TGIF expression, however, at high-concentrations (5–20 μM), ATO induced cell apoptosis. Using a promoter analysis, TGIF was transcriptionally regulated by ATO at the FOXO3A binding site (− 1486 to − 1479 bp) via the c-Src/EGFR/AKT pathway. Stable overexpression of TGIF promoted advancing the cell cycle into the S phase, and attenuated 20 μM ATO-induced apoptosis. Furthermore, blockage of the AKT pathway enhanced ATO-induced CDKN1A expression and resultant apoptosis in cancer cells, but overexpression of AKT1 inhibited CDKN1A expression. Therefore, we suggest that TGIF is transcriptionally regulated by the c-Src/EGFR/AKT pathway, which plays a role as a negative regulator in antagonizing ATO-induced CDKN1A expression and resultant apoptosis. Suppression of these antagonistic effects might be a promising therapeutic strategy toward improving clinical efficacy of ATO. - Highlights: • ATO-induced biphasic survival responses of cancer cells depend on low- or high-concentrations. • TGIF

  4. Potential role of sodium-proton exchangers in the low concentration arsenic trioxide-increased intracellular pH and cell proliferation.

    Directory of Open Access Journals (Sweden)

    Carmen Aravena

    Full Text Available Arsenic main inorganic compound is arsenic trioxide (ATO presented in solution mainly as arsenite. ATO increases intracellular pH (pHi, cell proliferation and tumor growth. Sodium-proton exchangers (NHEs modulate the pHi, with NHE1 playing significant roles. Whether ATO-increased cell proliferation results from altered NHEs expression and activity is unknown. We hypothesize that ATO increases cell proliferation by altering pHi due to increased NHEs-like transport activity. Madin-Darby canine kidney (MDCK cells grown in 5 mmol/L D-glucose-containing DMEM were exposed to ATO (0.05, 0.5 or 5 µmol/L, 0-48 hours in the absence or presence of 5-N,N-hexamethylene amiloride (HMA, 5-100 µmol/L, NHEs inhibitor, PD-98059 (30 µmol/L, MAPK1/2 inhibitor, Gö6976 (10 µmol/L, PKCα, βI and μ inhibitor, or Schering 28080 (10 µmol/L, H(+/K(+ATPase inhibitor plus concanamycin (0.1 µmol/L, V type ATPases inhibitor. Incorporation of [(3H]thymidine was used to estimate cell proliferation, and counting cells with a hemocytometer to determine the cell number. The pHi was measured by fluorometry in 2,7-bicarboxyethyl-5,6-carboxyfluorescein loaded cells. The Na(+-dependent HMA-sensitive NHEs-like mediated proton transport kinetics, NHE1 protein abundance in the total, cytoplasm and plasma membrane protein fractions, and phosphorylated and total p42/44 mitogen-activated protein kinases (p42/44(mapk were also determined. Lowest ATO (0.05 µmol/L, ~0.01 ppm used in this study increased cell proliferation, pHi, NHEs-like transport and plasma membrane NHE1 protein abundance, effects blocked by HMA, PD-98059 or Gö6976. Cell-buffering capacity did not change by ATO. The results show that a low ATO concentration increases MDCK cells proliferation by NHEs (probably NHE1-like transport dependent-increased pHi requiring p42/44(mapk and PKCα, βI and/or μ activity. This finding could be crucial in diseases where uncontrolled cell growth occurs, such as tumor growth, and

  5. Effect of glucose in mice after acute experimental poisoning with arsenic trioxide (As sub 2 O sub 3 )

    Energy Technology Data Exchange (ETDEWEB)

    Reichl, F.X.; Kreppel, H.; Fichtl, B.; Forth, W. (Muenchen Univ. (Germany, F.R.). Walter-Straub-Institut fuer Pharmakologie und Toxikologie); Szinicz, L. (Akademie des Sanitaets- und Gesundheitswesens der Bundeswehr, Garching (Germany, F.R.). Inst. fuer Pharmakologie und Toxikologie)

    1990-06-01

    In the present paper the effectiveness of glucose substitution was investigated in mice after acute experimental poisoning with As{sub 2}O{sub 3}. Four groups of ten mice each received As{sub 2}O{sub 3}, 12.9 mg/kg, s.c. After the injection the first group remained without further treatment, the second received saline every 2 h, the third 5% glucose, and the fourth 5% glucose + 0.12 IE insulin/kg i.p. Groups 5 and 6, five mice each, received either saline or glucose only. Group 7, five mice, remained without any treatment. Immediately after death the livers were removed for the enzymatic determination of glucose and glycogen. Mice receiving As{sub 2}O{sub 3} only died within 22 h. The mean survival time was 12.4 h. In mice receiving As{sub 2}O{sub 3} and after that saline, glucose, or glucose + insulin, an increase in the survival time to 30.8, 40.7, and 43.6 h, respectively, was observed. All mice which died showed a significant decrease in the liver glucose and glycogen content, compared to control animals. In livers of survivors, the glucose and glycogen content was not different to the control groups. The data support the assumption that carbohydrate depletion is an important factor in arsenic toxicity, and its substitution should be considered in the treatment of arsenic poisoning. (orig./MG).

  6. 亚砷酸和顺铂对骨肉瘤MG-63细胞生长的抑制作用比较%Comparison of arsenic trioxide and cisplatin on inhibiting osteosarcoma MG-63 cells

    Institute of Scientific and Technical Information of China (English)

    李雪松; 刘贾昆; 王文波

    2010-01-01

    率组间比较差异有统计学意义(F值分别为54.579、43.429、21.795,P<0.05或<0.01);对G1期抑制率(%)亚砷酸(78.26±5.24)和顺铂(80.48±2.81)与对照组(57.49±6.65)比较明显升高(P<0.05或<0.01).结论 亚砷酸和顺铂都可抑制骨肉瘤MG-63细胞生长,诱导细胞凋亡;亚砷酸作用快于顺铂,亚砷酸和顺铂对MG-63细胞的抑制作用发生在细胞周期中的G1期.%Objective To explore the inhibiting effects of arsenic trioxide and cisplatin on MG-63 cells. Methods Using MTT assay,flowcytometry,phase contrast microscopy and electron microscopy methods,the therapeutic effect of arsenic trioxide was studied for the osteosarcoma in the cultured MG-63 cells in vitro,and compared these effects with cisplatin. The inhibitory rotes of cell growth and the effect of apoptosis and cell cycle were compared between arsenic trioxide and cisplatin on MG-63 cells. Results The contrast phase microscope revealed the adhesion ability of normal groups was good and cellular morphology showed epithelium cells. But the celhdar morphology showed irregular arrangement in arsenic trioxide groups and cytoplasmic vacuoles in cisplatin group. Electron microscope revealed the globular plasmalemma ecphymas in cell surface of control groups,the enlarged crista mitochondriales and the double-deck membrane structure appeared clearly. But electron microscope revealed globular plasmalemma processes in cell surface of arsenic trioxide groups,thinned crista mitochondriales and clearly seen karyopycnosis and nuclear membrane of apoptotic cells. The globular plasmalemma processes in cell surface of cisplatin groups were separated,nuclear membrane thickened and chromatin were in sandy shape. Both arsenic trioxide and cisplatin inhibited effectively MG-63 cells growth. There was a significant difference in different groups of inhibition ratios to the growth of cells(all P < 0.05). In 2,4,8,16,32,64,128 hours,the inhibition ratios(%) of arsenic trioxide(56.31±0.03,70.00±0.06,79.84±0

  7. Budgetary impact of treating acute promyelocytic leukemia patients with first-line arsenic trioxide and retinoic acid from an Italian payer perspective.

    Directory of Open Access Journals (Sweden)

    Morgan Kruse

    Full Text Available The objective of this study was to estimate the net cost of arsenic trioxide (ATO added to all-trans retinoic acid (ATRA compared to ATRA plus chemotherapy when used in first-line acute promyelocytic leukemia (APL treatment for low to intermediate risk patients from the perspective of the overall Italian healthcare systemA Markov model was developed with 3 health states: stable disease, disease event and death. Each month, patients could move from stable to disease event or die from either state. After a disease event, patients discontinued initial treatment and switched to the other regimen as second-line therapy. Treatment regimens, efficacy and adverse events were derived from published sources and expert opinion; unit costs were collected from standard Italian sources. Clinical outcomes and costs for pre-ATO and post-ATO scenarios were combined with population and product utilization information to calculate the total budgetary impact using a 3-year time horizon; one-way sensitivity analyses were conducted. Three-year cumulative pharmacy costs for ATO+ATRA were €46,700 per-patient versus €6,500 for ATRA+chemotherapy; however, medical costs for ATO+ATRA were €12,300 per-patient versus €30,200 for ATRA+chemotherapy. The total budgetary impact was estimated to be an additional €127,300, €312,500 and €477,800 in the first, second and third years, respectively. The model was most sensitive to changes in the cost of the ATO+ATRA regimen during the consolidation phase. Budgetary impact models are valuable to payers making formulary decisions regarding the access and affordability of new medicines. The cost of treatment analysis showed that pharmacy costs for ATO+ATRA were higher than for ATRA+chemotherapy, while all other evaluated costs were lower for ATO+ATRA treated patients. The average budgetary impact was €305,900 per year overall, representing a 3.5% increase. Further research is needed to determine the cost-effectiveness of

  8. 三氧化二砷对支气管哮喘免疫及气道炎症的调控%Regulation on immunity and airway inflammation of bronchial asthma by arsenic trioxide

    Institute of Scientific and Technical Information of China (English)

    李坑; 龚素波; 徐礼; 张莉; 向旭东

    2011-01-01

    Bronchial asthma (asthma) is a kind of chronic inflammation of airway, which was involved in many kinds of cells and cellular elements, such as eosinophils, T lymphocytes, neutrophil granulocytes, mastocytes, alveolar epithelial cells, and so on. Arsenic trioxide can improve the asthmatic mice's pulmonary function in experiment, and own the ability of hold the patients' asthmatic symptoms in a better state for a long time. The recent researchs indicated that the arsenic trioxide can regulate immunity and inhibit airway inflammation through many effective processes, such as inhibiting humoral immunity and proliferation of T lymphocytes at skin and lung, down-regulating expression of inflammatory factors (IL-17, IL-18, IL-23,etc), and inducing apoptosis of neutrophil granulocytes by endoplasmic reticulum stress pathway. The newest studies about the regulation on immunity and airway inflammation of asthma by arsenic trioxide were summarized, and some possible research orientation was previewed.%支气管哮喘(简称哮喘)是一种由多种细胞(嗜酸粒细胞、T细胞、中性粒细胞、肥大细胞及肺泡上皮细胞等)及细胞组分参与的气道慢性炎症性疾病.三氧化二砷在动物实验中能改善哮喘小鼠的肺功能,在临床治疗中能使患者的哮喘症状得到长期控制.新近研究表明:三氧化二砷能明显抑制小鼠的体液免疫反应,抑制小鼠的肺、皮肤等组织的T细胞增殖,能下调IL-17、IL-18和IL-23等多种炎症因子的分泌,并且通过内质网应激途径诱导中性粒细胞凋亡,从而调节免疫,抑制炎症.文章综述了三氧化二砷调控哮喘免疫及气道炎症的最新研究进展,并进行了展望.

  9. 三氧化二砷与HAG方案治疗骨髓增生异常综合征的对比研究%Comparision of between arsenic trioxide and HAG regimen in the treatment of myelodysplastic syndrome

    Institute of Scientific and Technical Information of China (English)

    张静; 徐敬根

    2012-01-01

    Objective HAG regimen ( Homoharringtonine and Low-dose Cytosine Arabinoside Combined with G-CSF or GM-CSF)is an important regimen for refractory anemia with excess blasts of myelodysplastic syndrome ( MDS-RAEB), but the side effect is severe. This study aims to compare the short-term efficiency, toxicity and side effect between arsenic trioxide and HAG regimen in the treatment of MDS-RAEB. Methods All patients were randomly divided into two groups: A group and B group. 20 cases in A group:were treated with HAG regimen for remission induction and consolidation therapy. 20 cases in B group were Arsenic trioxide was administered 10 mg/d, intravenous infusion, 14 times per month, 2 ~3 weeks interval for a course of treatment. Results Response rates were 70. 0% (group A) and 80. 0% ( group B). The response rate between two groups were not statistical difference (P > 0. 05). The incidences of infection which exceed grade H were 43. 8% ( group A) and 9. 09 % (group B) , and the incidences of hemorrhage which exceed grade II were 37. 5% ( group A) , and 12. 1% ( group B) , with statistical difference between the two groups(P<0.05). Conclusion The therapeutic efficiency of arsenic trioxide was similarly to that of HAG regimen and side-effect of arsenic trioxide were milder than that of HAG regimen.%目的 HAG方案是目前治疗骨髓增生异常综合征难治性贫血伴原始细胞增多(MDS-RAEB)的重要化疗方案之一,但不良反应仍较大.本研究的目的是比较三氧化二砷与HAG治疗MDS-RAEB的近期疗效和不良反应.方法 将40例骨髓增生异常综合征患者随机分成A组(预激方案20例)和B组(三氧化二砷20例),化疗2~3个周期,评价疗效.结果 A组有效率70.0%,B组有效率80.0%,两组比较,差异无统计学意义(P>0.05);A组≥Ⅱ级感染的发生率为43.8%,≥Ⅱ级出血(需予局部压迫、药物止血或血小板输注等相应处理)的发生率为37.5 %;B组≥Ⅱ级感染发生率为9.09

  10. 亚砷酸腔内注射治疗恶性胸腔积液的临床观察%Clinical observation of the treatment of malignant pleural effusion by injecting arsenic trioxide into pleural cavity

    Institute of Scientific and Technical Information of China (English)

    孟令新; 迟玉华; 丁兆军; 杨淑光; 王传艳; 张桂芳

    2014-01-01

    目的:评价亚砷酸胸腔注射治疗恶性胸腔积液的临床价值。方法:恶性胸腔积液患者68例,均经细胞学和病理学确诊。随机分为治疗组和对照组,在胸膜腔积液充分引流后,治疗组36例,胸膜腔内注射亚砷酸10-20mg,每天或隔日1次,连续3次。对照组32例,胸膜腔内注射博莱霉素30mg/ m2,7天1次,共1-2次。观察疗效、毒副反应、生活质量。结果:治疗组 CR 10例(27.78%),PR 16例(44.44%),总有效率为72.22%(26/36);对照组 CR 8例(25.00%),PR 15例(46.88%),总有效率为71.88%(23/32),两组有效率差异无显著性(P ﹥0.05)。治疗组注药后胸痛反应明显低于对照组(P ﹤0.05),胃肠道反应、骨髓抑制、发热反应两组间无明显差异(P ﹥0.05)。治疗后两组 KPS 评分均有增加,治疗前后比较有明显差异(P ﹤0.05)。结论:亚砷酸胸腔注射治疗恶性胸腔积液是一种有效、安全的方法。%Objective:To evaluate the clinical value of arsenic trioxide in treating malignant Pleural effusion by in-jecting into Pleural cavity. Methods:Sixty - eight Patients,required to have a cytologically Positive Pleural effusion or a Positive Pleural bioPsy in the Presence of an exudative effusion. After the accumulation of Pleural fluid had been ad-equately drained,36 Patients were randomized to Arsenic trioxide grouP,receiving arsenic trioxide 10 - 20mg,once a day or once two days,on 3 successive times,which were administered via chest tube or directly injected into Pleural cavity. Then the efficacy,toxicity and Perform ancestatus were evaluated. Results:In the Arsenic trioxide grouP,10 Pa-tients(27. 78% )achieved CR and 16 Patients(44. 44% )PR,the overall resPonse rate was 72. 22%(26 / 36). The control grouP 8 Patients(25. 00% )achieved CR and 15 Patients( 46 . 88 % )PR,and the overall resPonse rate was 71. 88%(23 / 32). The two grouPs had no significant

  11. 三氧化二砷在消化系恶性肿瘤治疗中的作用%Role of arsenic trioxide in the treatment of malignant tumors of the digestive system

    Institute of Scientific and Technical Information of China (English)

    常圆; 杨甜; 关景明

    2012-01-01

    三氧化二砷(arsenic trioxide,As2O3),中药名为砒霜,在临床上的应用有悠久的历史,经过多年的实验室研究和临床应用,AS2O3在抗肿瘤方面有确切的疗效,他是治疗急性早幼粒细胞白血病的有效药物之一,且不良反应较小,其主要机制为诱导细胞凋亡.目前As2O3已用于多种实体肿瘤的治疗,且在消化系肿瘤如肝癌的临床治疗中,疗效确切.近年来,在消化系统肿瘤的体外细胞系和体内动物模型的研究中均发现,As2O3能够诱导胃癌、胰腺癌、肝癌和结肠癌细胞凋亡,同时对癌细胞的生长起抑制作用.因此,研究As2O3在消化系恶性肿瘤防治中的作用具有重要意义.本文结合国内外文献对As2O3在治疗消化系恶性肿瘤中的作用作一综述.%Arsenic trioxide (As2O3), also named arsenic, is a main ingredient of numerous traditional Chinese herbal recipes and has a long history of clinical application. It has positive anticancer effects and is effective in treating acute promyelocytic leukemia without toxic and side effects. As2O3 can induce apoptosis of cancer cells. In recent years, it has been found that As2O3 has an apoptosis-promoting effect on tumor cells in many human solid tumors, including liver cancer. Many in vitro and in vivo studies using digestive tract tumor cell lines or animal model have found that As2O3 can induce apoptosis and inhibit growth of digestive tract cancer cells. Therefore, As2O3 may have an important role in the prevention of malignant tumors of the digestive system. In this article, we discuss the possible cellular and molecular mechanisms by which As2O3 induces apoptosis of digestive tract cancer cells.

  12. Improvement on the Determining Method of Particulate Arsenic and Arsenic Compounds and Arsenic Trioxide Vapour in Atmosphere%测定环境空气中砷及其化合物的方法改进

    Institute of Scientific and Technical Information of China (English)

    郎雅娣; 梁静; 鹿海峰

    2013-01-01

    对《空气和废气监测分析方法》中砷的采样和测定方法进行了改进,并在云南某炼铜厂环境空气中含砷监测进行了实际验证.结果表明,方法的检出限、精密度、准确度均能满足测定的要求,并且更适合测定高浓度砷.%The "air emission monitoring and analysis methods" in the sampling and testing methods for arsenic has been improved. The method has been verified in a copper smelter in Yunnan. The detection limits, precision, accuracy can content the detect demand and this method is more suitable for determination of high concentrations of arsenic.

  13. Arsenic

    Science.gov (United States)

    ... of countries, including Argentina, Bangladesh, Chile, China, India, Mexico, and the United States of America. Drinking-water, ... ingestion of inorganic arsenic include developmental effects, neurotoxicity, diabetes, pulmonary disease and cardiovascular disease. Arsenic-induced myocardial ...

  14. Interventional Treatment Effects of Arsenic Trioxide for Advanced Primary Liver Cancer%三氧化二砷在中晚期原发性肝癌介入治疗方面的作用

    Institute of Scientific and Technical Information of China (English)

    侯毅斌; 刘琦; 段光峰; 萧慧菊; 王峻; 汤日杰

    2015-01-01

    Objective:To study the clinical effects and safety of arsenic trioxide for interventional treatment of advanced primary liver cancer. Method:126 patients with primary liver cancer in our hospital received the interventional treatment and randomly divided into two groups, 63 cases each group. The observation group were treated with arsenic trioxide and UFL; control group were treated with epirubicin and UFL. The treatment effect and adverse reactions of two groups were compared. Result: After interventional treatment , the total effective rate of observation group(74.6%) was significantly higher than that of control group(39.7%)(P<0.01); during treatment, the major adverse reactions were bone marrow suppression, nausea and vomiting, fever, pain, hepatic injury, etc. The symptoms were effectively relieved upon taking measures. Conclusion:The interventional treatment of arsenic trioxide for liver cancer can effectively and easily alleviate the patients’ pains, promote the clinical treatment and has fewer adverse reactions. It is worthy of clinical promotion.%目的:探讨三氧化二砷在中晚期原发性肝癌介入治疗中的临床效果。方法:选取我院收治的确诊为原发性肝癌的患者126例,均给予介入治疗。将其随机分成两组,每组63例。观察组患者治疗方案为三氧化二砷+超液态碘油;对照组患者治疗方案为表阿霉素(表柔比星)+超液态碘油。对比两组治疗效果以及不良反应发生情况。结果:126例肝癌患者给予药物介入治疗后,观察组总有效率为74.6%,对照组总有效率为39.7%,明显看出加入三氧化二砷介入治疗后,总有效率显著提高(P<0.01);治疗中主要出现的不良反应为骨髓抑制、恶心呕吐、发热、疼痛、肝功能损伤等,采取措施后可有效缓解。结论:三氧化二砷应用于肝癌介入治疗,有效减轻了患者的痛苦,改善了临床治疗效果,操作简单,不良反应少,值得临床推广。

  15. Refractory and recurrent malignancies with arsenic trioxide MDT analysis influence on prognosis%难治及复发性恶性血液病采用三氧化二砷联合化疗对预后影响

    Institute of Scientific and Technical Information of China (English)

    安婕; 唐雯

    2014-01-01

    目的:观察三氧化二砷联合化疗方案治疗难治及复发性恶性血液病的效果。方法:随机从我院2009年6月~2014年6月收治的难治及复发性恶性血液病患者中抽取60例作为研究对象,根据治疗方案将其分为对照组和观察组,每组各30例。其中对照组使用单纯化疗方案治疗,观察组则使用三氧化二砷联合化疗的方案治疗,对比两组的临床效果和毒性反应。结果:经对比,观察组患者的总有效率为86.67%,显著高于对照组的66.67%,差异具有统计学意义(P<0.05)。同时,观察组的毒性反应发生率为30%,显著低于对照组的66.67%,差异具有统计学意义(P<0.05)。结论:对难治及复发性恶性血液病采用三氧化二砷联合化疗治疗具有显著疗效,降低不良反应,有助于改善患者的预后。%Objective: To explore the use of arsenic trioxide and combination in the treatment of refractory and the prognosis of recurrent malignancies effects and adverse reactions. Methods: Random from our hospital in June 2009~June 2014 patients with refractory and recurrent malignancies treated were extracted 60 cases as the research object, according to the treatment plan will be divided into control group and observation group, 30 cases in each group. , including control group using pure chemotherapy regimen for observation group joint solution with arsenic trioxide and chemotherapy treatment,compared two groups of clinical effect and toxic reaction. Results:By contrast, the observation group the total effective rate of the patients were 86.67%, significantly higher than that of control group 66.67%, and the difference is statistically significant(P<0.05). Incidence of toxic effects of at the same time, the observation group was 30%, significantly lower than the control group 66.67%, and the difference is statistically significant (P<0.05). Conclusion: The refractory and recurrent malignancies with

  16. 三氧化二砷联合顺铂治疗恶性胸腔积液的临床研究%A Clinical Study on Arsenic Trioxide Combined with Cisplatin in the Treatment of Malignant Pleural Effusion

    Institute of Scientific and Technical Information of China (English)

    杨雪梅; 陈远航; 曾守群; 戴刚毅; 曾贵林; 孟又胜

    2013-01-01

    Objective To evaluate the efficacy and side-effects of arsenic trioxide combined with eisplatin in treating malignant pleural effusion by injecting it into the pleural cavity.Methods Sixty patients with malignant hydrothorax diagnosed between September 2011 and September 2012 were randomized into two groups.After the accumulation of pleural fluid had adequately drained,30 patients were randomized to treatment group,receiving arsenic trioxide 20 mg plus cisplatin 60 mg once a week for 3 times,and the other 30 patients were randomized to control group,receiving cisplatin 60 mg once a week for 3 times.Then the efficacy and toxicity were evaluated.Results The overall response rates in the treatment group and in the control group were 93.3% and 56.7% (P < 0.05),respectively.The total modification rates in the treatment group and the control group were 70% and 40% (P < 0.05),respectively.There was no difference in toxicity between the two groups.Condusions Pleural cavity infusion of arsenic trioxide combined with cisplatin has combined synergies.The treatment is well tolerated with little adverse toxic reaction.%目的 观察三氧化二砷联合顺铂腔内注射治疗恶性胸腔积液的疗效和毒副反应.方法 2011年9月-2012年9月,将恶性胸腔积液患者60例,随机分为治疗组和对照组,每组各30例.在胸腔积液充分引流后,治疗组胸腔内注射三氧化二砷20 mg联合顺铂60 mg;对照组只给予胸腔灌注顺铂60 mg,胸腔灌注化学疗法药物两组均1次/周,共3次.观察疗效及不良反应.结果 治疗组和对照组的有效率分别为93.3%和56.7% (P<0.05).治疗组和对照组的一般状况改善率分别为70.0%和40.0% (P<0.05).两组的不良反应相近.结论 三氧化二砷联合顺铂腔内注射治疗恶性胸腔积液具有协同增效作用,不良反应小.

  17. Effect of Arsenic Trioxide on Cell Cycle and Apoptosis of Multidrug Resistant K562/A02 Cell Line%三氧化二砷对K562/A02细胞的凋亡及细胞周期的影响

    Institute of Scientific and Technical Information of China (English)

    陆跃武; 耿华云; 张峰; 盖灿; 韩慧杰; 孙海英

    2012-01-01

    Objective: To explore the effect of arsenic trioxide on cell cycle and apoptosis of K562/A02 cells and its possible mechanism. Methods: Adriamycin (Adr) resistant K562/A02 were treated with arsenic trioxide (non-cytotoxic concentration at 4.0μmol/L, 5.0μmol/L) or without arsenic trioxide (control), flow cytometry was used to evaluate apoptosis and cell cycle distribution, and change of the expression level of NF-K Bp65 protein in nucleus was detected by western blot. Results: As compared with control arsenic trioxide significantly increased the rate of apoptosis, arrested cells in G0/G1 phase and reduced the levels of NF-K Bp65 protein in nucleus (allP<0.05). Conclusion: The underlying mechanism for arsenic trioxide to promote apoptosis of K562/A02 and suppress cell proliferation lies in its impact on NF-K Bp65 protein expression.%目的:研究三氧化二砷对多药耐药急性白血病细胞株K562/A02凋亡与细胞周期的影响及可能机制.方法:取阿霉素(Adr)的耐药白血病细胞株分为未加药的对照组及加入不同浓度的三氧化二砷(其终浓度为4.0μmol/L、5.0μmol/L)组,流式细胞仪检测细胞凋亡及细胞周期分布,Western blot方法检测不同浓度三氧化二砷对K562/A02细胞核NF-κ Bp65蛋白水平.结果:与对照组比较,三氧化二砷可显著增加Adr对K562/A02细胞凋亡率,阻滞细胞于G0/G1期,降低K562/A02细胞胞核中NF-kB p65的表达(P均<0.05).结论:三氧化二砷可能是通过抑制NF-kB的胞内活化转位,从而促进K562/A02细胞凋亡及抑制细胞增殖.

  18. [Acute arsenic poisoning].

    Science.gov (United States)

    Montelescaut, Etienne; Vermeersch, Véronique; Commandeur, Diane; Huynh, Sophie; Danguy des Deserts, Marc; Sapin, Jeanne; Ould-Ahmed, Mehdi; Drouillard, Isabelle

    2014-01-01

    Acute arsenic poisoning is a rare cause of suicide attempt. It causes a multiple organs failure caused by cardiogenic shock. We report the case of a patient admitted twelve hours after an ingestion of trioxide arsenic having survived thanks to a premature treatment.

  19. [Acute arsenic poisoning].

    Science.gov (United States)

    Montelescaut, Etienne; Vermeersch, Véronique; Commandeur, Diane; Huynh, Sophie; Danguy des Deserts, Marc; Sapin, Jeanne; Ould-Ahmed, Mehdi; Drouillard, Isabelle

    2014-01-01

    Acute arsenic poisoning is a rare cause of suicide attempt. It causes a multiple organs failure caused by cardiogenic shock. We report the case of a patient admitted twelve hours after an ingestion of trioxide arsenic having survived thanks to a premature treatment. PMID:25486670

  20. Silicon molybdenum blue spectrophotometric determination of silicon dioxide in arsenic trioxide%硅钼蓝分光光度法测定三氧化二砷中二氧化硅

    Institute of Scientific and Technical Information of China (English)

    谢辉; 赖心; 黄葡英

    2011-01-01

    In this study, hydrochloric acid was added into arsenic trioxide to remove arsenic by heating. The obtained residual was dissolved with sodium hydroxide. After acidification with nitric acid,silicon could form silicon molybdenum yellow complex with molybdate at pH 0. 9 using ammonium molybdate as color developer. With sulfuric acid increase the acidity, the complex was reduced to silicon molybdenum blue complex by ascorbic acid. The content of silicon dioxide was determined by spectrophotometry. The maximum absorption wavelength of silicon molybdenum blue complex was 813 nm. The relative standard deviations (RSD, n=6) were 1. 6 %-1. 9%. The determination results of this method were consistent with those obtained by ICP-AES.%研究了在三氧化二砷中加入盐酸,加热除砷,所得残渣用氢氧化钠溶解,硝酸酸化后,以钼酸铵为显色剂,在pH 0.9条件下,硅与钼酸盐形成硅钼黄络合物,用硫酸提高酸度,以抗坏血酸为还原剂,使硅形成稳定的硅钼蓝络合物,采用分光光度法测定其中的二氧化硅含量.硅钼蓝络合物最大吸收波长位于813 nm处.本法相对标准偏差(RSD)为1.6%~1.9%(n=6),测定结果与.ICP-AES法的结果相一致.

  1. As2O3联合Aspirin对诱导肝癌细胞凋亡的影响%Aspirin enhances arsenic trioxide-induced apoptosis of hepatocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    郝立晓; 刘铁夫

    2012-01-01

    AIM: To investigate the effect of aspirin combined with arsenic trioxide (As2O3) on human hepatocarcinoma cell line Bel-7402 and to explore the possible mechanisms involved.METHODS: Cultured Bel-7402 cells were incubated with different concentrations of aspirin and As2O3, alone or in combination. After treatment, cell morphology was observed using an inverted microscope, cell proliferation was determined by MTT assay, cell apoptosis was measured by flow cytometry with annexin V/ propidium iodide staining, and cell cycle progression was analyzed by fluorescence-activated cell sorting.RESULTS: As2O3 and aspirin showed different degrees of inhibitory effect on the growth of Bel-7402 cells, and both were concentration-dependent. The two drugs had a synergistic effect, and the inhibitory effect in the combination group was more significant than those in the two monotherpay groups (both P < 0.05). Compared to treatment with 2.0 μmol/L As2O3 alone, treatment with 2.0 μmol/L As2O3 combined with 0.2 mmol/L aspirin significantly increased the apoptosis rate (5.64% ± 0.56% vs 7.35% ± 0.62%, P < 0.05), decreased the percentage of cells in G1 phase (0.52% ± 0.64% vs 32.03% ± 0.97%), and increased the percentages of cells in G2 phase or S phase (9.57% ± 0.82% vs 13.66% ± 0.82%, 50.41% ± 0.32% vs 54.37% ± 0.69%).CONCLUSION: Aspirin enhances As2O3-induced apoptosis of Bel-7402 cells possibly by altering cell cycle progression.%目的:观察As2O3与Aspirin联合应用对肝癌细胞Bel-7402的影响,并探讨其作用机制.方法:体外培养肝癌Bel-7402细胞,Aspirin、As2O3不同浓度孵育细胞.倒置显微镜观察细胞形态学改变,四甲基偶氮唑蓝(MTT)法检测As2O3和Aspirin单独及联合应用对Bel-7402细胞增殖情况的影响,流式细胞术观察细胞凋亡情况,并通过流式软件分析细胞周期变化.结果:As2O3及Aspirin对肝癌Bel-7402细胞生长均呈不同程度的抑制,且呈浓度依赖性.二者联合具有协同作用,药

  2. Acute and chronic arsenic toxicity

    OpenAIRE

    Ratnaike, R.

    2003-01-01

    Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption o...

  3. 三氧化二砷对裸鼠宫颈癌移植瘤的作用及机制%Effects and Mechanism of Arsenic Trioxide on Growth of Cervical Cancer in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    林晨; 拉莱·苏祖克; 史永华; 魏琴

    2011-01-01

    目的 研究三氧化二砷(arsenic trioxide,ATO,As2O3)对宫颈癌 HeLa 细胞裸鼠移植瘤生长的作用及机制.方法 建立裸鼠移植瘤模型,分为低浓度 As2 O3组[2mg/(kg·d)],高浓度As2O3 组[5mg/(kg·d)],顺铂(DDP)组[3mg/(kg·d)]及阴性对照组(0.9%氯化钠0.2ml/d),连续给药10d,观察抑瘤率及药物对裸鼠的影响.透射电子显微镜观察肿瘤的超微结构,免疫组织化学检测p-P38和Caspase-3的表达.结果 低浓度 As2 O3,高浓度 As2 O3及 DDP 的抑瘤率分别为22.95%、54.86%和54.48%,后两者的抑瘤率与阴性对照组的差异有统计学意义(P<0.05),但DDP的不良反应大.p-P38和 Caspase-3在As2 O3组的表达明显高于阴性对照组(P<0.05).结论 As2O3可通过诱导肿瘤细胞凋亡抑制宫颈癌移植瘤的生长.%Objective To explore the inhibitory effect of arsenic trioxide(ATO, As2O3 ) on the tumor growth of cervical cancer cell line HeLa subcutaneously implanted in nude mice and its mechanism.Methods Human cervical cancer xenografted model was established in nude mice. The tumor-bearing nude mice were randomly divided into the experimental groups: ATO low dose group [2mg/(kg ·d)], ATO high dose group [5mg/(kg · d)], DDP positive control group [3rng/(kg · d)], saline negative control group(0. 9%NaCl 0. 2ml/d). The drugs were administered intraperitoneally for 10 consecutive days. To observe the tumor inhibition rate and effects of drugs. Ultramicrostructure feature of tumor was observed under electron microscope. Immunohistochemistry was used to measure the expression of p-P38 and Caspase-3. Results Inhibited tumor volume of ATO low and high dose groups and DDP positive control group was 22. 95% ,54. 86% and 54. 48%, respectively. The inhibited effect of ATO 5mg/kg/d group was similar with DDP 3mg/kg/d group, but the toxic effect of DDP was higher than ATO. The expression of p-P38 and Caspase-3 was higher than negative control group (P <0. 05). Conclusion ATO can inhibit

  4. 载三氧化二砷的PEG—PLGA隐性纳米粒的制备及体外研究%Preparation and in vitro Studies of Stealth PEGylated PLGA Nanoparticles as Carriers for Arsenic Trioxide

    Institute of Scientific and Technical Information of China (English)

    王志清; 刘卫; 徐辉碧; 杨祥良

    2007-01-01

    The aim of this study was to prepare arsenic trioxide (ATO)-loaded stealth PEGylated PLGA nanoparticles (PEG-PLGA-NPs) and to assess the merits of PEG-PLGA-NPs as drug carriers for ATO delivery. PEG-PLGA copolymer was synthesized with methoxypolyethyleneglycol (Mw=5000),D,L-lactide,and glycolide by the ring-opening polymerization method. Amorphous ATO was transformed into cubic crystal form to increase its solubility in the organic solvent. ATO-loaded PEG-PLGA-NPs were prepared by the modified spontaneous emulsification solvent diffusion (SESD) method,and the main experimental factors influencing the characteristics of nanoparticles were investigated,to optimize the preparation. To confirm the escape of PEG-PLGA-NPs from phagocytosis by phagocytes,PEG-PLGA-NPs labeled rhodamine B uptake by murine peritoneal macrophages (MPM) were analyzed by flow cytometry. The results showed that the physicochemical characteristics of PEG-PLGA-NPs were affected by the type and concentration of the emulsifiers,polymer concentration,and drug concentration. ATO-loaded PEG-PLGA-NPs,with particle size of 120.8nm,zeta potential of -10.73mV,encapsulation efficiency of 73.6%,and drug loading of 1.36%,were prepared under optimal conditions. The images of transmission electron microscopy (TEM) indicated that the optimized nanoparticles were near spherical and without aggregation or adhesion.The release experiments in vitro showed the ATO release from PEG-PLGA-NPs exhibited consequently sustained release for more than 26d,which was in accordance with Higuchi equation. The uptake of PEG-PLGA-NPs by MPM was found to decrease markedly compared to PLGA-NPs. The experimental results showed that PEG-PLGA-NPs were potential nano drug delivery carriers for ATO.

  5. 三氧化二砷体外对哮喘患者外周血T细胞凋亡和白细胞介素4分泌的影响%Effects of arsenic trioxide on apoptosis and interleukin-4 release of peripheral T cells from asthmatic patients in vitro

    Institute of Scientific and Technical Information of China (English)

    覃冬云; 黄韧; 吴铁

    2007-01-01

    目的 探讨三氧化二砷治疗哮喘的可能机制.方法 分离21例哮喘患者和20例健康对照者外周血T 细胞,分别加入三氧化二砷(0.1 mg·L-1)或地塞米松(5 mg·L-1)培养24 h.用ELISA方法检测培养上清液中白细胞介素4(IL-4)的含量,用荧光显微镜、流式细胞术和细胞色素c 试剂盒检测细胞凋亡.结果 哮喘患者T细胞自发释放IL-4较健康对照者明显增多;三氧化二砷对健康对照者T细胞IL-4的释放无影响,对哮喘患者T细胞IL-4释放增加具有抑制作用;地塞米松可使两组T细胞IL-4的释放明显降低.哮喘患者外周血T细胞体外培养24 h凋亡百分率较健康对照者明显降低,细胞浆细胞色素c含量降低;三氧化二砷明显增加哮喘患者T细胞凋亡的百分率和细胞色素c的含量,对健康对照者作用不明显;地塞米松可使两组的T细胞凋亡百分率和细胞色素c含量增加.结论 三氧化二砷治疗哮喘的机制可能与诱导哮喘患者T细胞凋亡和IL-4分泌减少有关.%AIM To study the possible mechanism of the treatment of arsenic trioxide on asthma. METHODS T cells isolated from 21 asthmatic patients and 20 healthy controls were treated with arsenic trioxide (0.1 mg·L-1) or dexamethasone (5 mg·L-1),in vitro, for 24 h. Interleukin-4 (IL-4) levels in supernatants from T cells were quantified with ELISA. Cell apoptosis was measured by using fluorescence microscopy, flow cytometry and cytochrome c ELISA kit. RESULTS T cells of asthmatic patients spontaneously released more IL-4 than that of healthy controls. Arsenic trioxide significantly decreased IL-4 release of T cells from asthmatic patients, which was more obvious compared with healthy controls. Dexamethasone decreased IL-4 release in both groups. Apoptosis percentage and cytochrome c content in cytoplasm of T cells from asthmatic patients were lower than those from healthy controls. Arsenic trioxide significantly increased the apoptosis percentage and

  6. 三氧化二砷抑制NB4细胞增殖机制的探讨%Study on the mechanism of arsenic trioxide inhibiting NB4 cells proliferation

    Institute of Scientific and Technical Information of China (English)

    杨国姿; 李薇; 马克威; 杜忠华; 李玲

    2009-01-01

    Objective To explore the molecular mechanisms of arsenic trioxide (As2O3) inhibiting NB4 cells proliferation. Methods The Janus kinase 1 (JAK1) protein level and its phosphorylation level in NB4 cells was detected by Western blots. NB4 cells were transfected with JAK1 siRNA or JAK1 plasmid to make JAK1 gcne silenced or overcxpressed. The inhibition of NB4 cells proliferation was measured by MTT as-say and Trypan blue exclusion respectively. The variation of phosphorylation level of JAK1 and the cell cycle inhibitor P21 were determined by Western blots. Results JAK1 protein was expressed stably in NB4 cells, with no phosphorylation. The phosphorylation of JAK1 was enhanced after the NB4 cells treated with As2O3. After NB4 cells transfected with JAK1 siRNA, the expression level of JAK1 was obviously lower than that of in the non-specific siRNA group and blank control group. The effect of As2O3 inhibiting NB4 cells proliferation was weaker in the JAK1 siRNA transfected group. The inhibiting rate of 4 μmol/L As2O2 on NB4 cells prolif-erition of JAK1 siRNA group was 49.12% being lower than that of the non-specific siRNA group (74.58%) and control group (72.33%). After NB4 cells transfected with JAK1 plasmid, the JAK1 expression level in wild-type and mutant type plasmid groups were significantly higher than those in the empty plasmid group, moreover the effect of As2O3 inhibiting proliferation was stronger in wild-type plasmid group. The inhibiting rate of 4 μmol/L As2O3 on NB4 cells proliferition of wild-type plasmid group was 69.53% being higher than that of the mutant cype JAK1 plasmid group (37.26%) and the empty plasmid group (39.61%). The ex-pression level of P21 was up-regulated after the NB4 cells treated with As2O3. Conclusion JAK1 is ex-pressed stably in NB4 cells, but has no activity. Arsenic trioxide inhibits the proliferation of NB4 cells through activating the JAK1. P21 is up-regulated after arsenic trioxide activated the JAK1 to inhibit the prolif

  7. 三氧化二砷在系统性红斑狼疮治疗中的应用%The application of arsenic trioxide in the treatment of systemic lupus erythematosus

    Institute of Scientific and Technical Information of China (English)

    康俞莉; 章强强

    2013-01-01

    As an autoimmune disease, systemic lupus crythematosus is caused by genetics, environment, immune factors, etc, which results in multi-organs and multi-system's damage. It has complex pathogenesis, diverse clinical manifestations and the progress conditions ongoing deteriorated. Traditionally, combining glucocorticoid with immunosuppressant is the main treatment for systemic lupus erythematosus, while cytotoxic drugs or biological modifiers are supplemented for severe patients, but the result is not satisfactory, and these drugs often lead to tremendous side effects. In recent years, a large number of basic and clinical trials in domestic and abroad indicate that immune factors play a important role in the pathogenesis of SLE. Arsenic trioxide (ATO) can effectively alleviate and control the symptoms of SLE, what's more, many in-depth research have attempted to figure out the mechanism of ATO to the treatment of SLE. This review intends to make a brief introduction of pharmacodynamic characteristics of ATO as well as its clinical application, and mechanism of ATO in the treatment of SLE.%系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种由遗传、环境、免疫等多种因素参与引起的多器官、多系统损害的自身免疫性疾病,其发病机制复杂,临床表现多样,病情多呈进行性发展.对于SLE的治疗,传统上主要以精皮质激素联合免疫抑制剂为主,严重者辅以细胞毒药物或生物调节剂,但总体疗效欠佳,且不良反应较大.近年来,大量的基础研究和临床试验表明,免疫因素在SLE发病机制中起主要作用, 三氧化二砷(ATO)能有效缓解、控制SLE的症状,并且对ATO治疗SLE的作用机制也进行了许多深入的研究.该文拟从ATO的药效特性、临床应用、作用机制等方面对ATO治疗SLE的研究现况做一概述.

  8. Term Effect of Arsenic Trioxide Treatment of Advanced Hepatocellular Carcinoma%三氧化二砷治疗中晚期原发性肝癌的近期疗效

    Institute of Scientific and Technical Information of China (English)

    林志宇; 马闻; 付榆; 乔青; 宿向东

    2014-01-01

    Objective To study the clinical therapeutic effects and the side effects of arsenic trioxide(As2O3)when used to treat middle or advanced primary hepatocellular carcinoma by interventional ways. Methods 33 cases with single agent arsenic trioxide 10 mg/d and saline infusion for 14 d for 1 cycles, 2 weeks intermittent, at least 2 cycles. Results All the 4 patients with PR, 22 cases of NC, 7 cases of PD, the efifciency of 12%. Clinical beneift rate:78.8%;pain relief rate was 82.7%, the quality of life of patients with 81.8% increase; adverse reaction of the treatment mainly Ⅰ to Ⅱ gastrointestinal reaction and hematologic toxicity, liver function impairment mild. Conclusion Arsenic trioxide in the treatment of middle or advanced primary hepatocellular carcinoma have the good curative effect, less adverse reaction, is a good choice for l hepatocellular carcinoma treatment, worthy of clinical application.%目的:观察三氧化二砷治疗中晚期原发性肝癌的近期疗效及不良反应。方法对33例采用单药三氧化二砷10mg/d加入生理盐水静脉滴注连续14d为1个周期,间歇2周,至少使用2个周期。结果全组4例PR,22例NC,7例PD,客观有效率12%。临床受益率:78.8%;疼痛缓解率为82.7%,81.8%患者生存质量提高;该治疗方案不良反应主要表现为Ⅰ~Ⅱ度胃肠道反应和血液学毒性,轻度的肝功能损害。结论三氧化二砷治疗中晚期原发性肝癌有较好疗效,不良反应较小,是肝癌治疗用药的较佳选择,值得临床推广。

  9. Effect of arsenic trioxide on expression of MGMT and VEGF in irradiated human lung cancer cells%三氧化二砷对照射后人肺癌细胞MGMT和VEGF表达的影响

    Institute of Scientific and Technical Information of China (English)

    任庆兰; 陈小品; 吴永忠; 金丹; 高枫; 李少林

    2009-01-01

    目的:本文探讨三氧化二砷(Arsenic trioxide,As_2O_3)对受照后人肺癌A2细胞株MGMT和VEGF表达的影响.方法:设立空白对照组、照射组(直线加速器X射线照射,2Gy)、As_2O_3组(1.0μmol/L As_2O_3)、As_2O_3+照射组(1.0μmol/L As_2O_3+X射线照射,2Gy).平板克隆形成试验测定各实验组细胞集落形成率,用RT-PCR和免疫组化检测MGMT(甲基鸟嘌呤甲基转移酶)、VEGF(血管内皮生长因子)基因和蛋白水平的变化.结果:As_2O_3+照射组细胞集落形成率较As_2O_3组及照射组明显下降.与As_2O_3组或照射组比较差异具有著性(P<0.01).As_2O_3+照射组细胞MGMT、VEGF基因表达明显减少,而且MGMT、VEGF蛋白的表达明显降低,与As_2O_3组或照射组比较差异具有显著件(P<0.01).结论:As_2O_3能使受照后人肺癌A2细胞MGMT、VEGF基因及蛋白表达水平明显下调卜,可能是As_2O_3对人肺癌细胞辐射增敏的机制之一.

  10. Combination therapy with arsenic trioxide and parthenolide against pancreatic cancer cells%三氧化二砷联合小白菊内酯的抗胰腺癌作用

    Institute of Scientific and Technical Information of China (English)

    刘志宇; 田蓝天; 王巍

    2011-01-01

    Objective To investigate the anticancer effect and potential mechanism of combination treatment with arsenic trioxide ( ATO ) and parthenolide ( PTL) in human pancreatic cancer cells. Methods Viability of pancreatic carcinoma cell lines, PANC-1 and BxPC-3, were determined by trypan blue exclusion, apoptosis was detected by annexin V/propidium iodide double stain, DAPI was used to observe the nuclei, reactive oxygen species and HO-1 levels were determined by flow cytometry and Western blot. Results The combination of PTL and ATO inhibited the growth of pancreatic tumor cell lines much greater than each agent alone. The PTL/ATO treatment induced apoptosis and elevated reactive oxygen species and HO-1 levels. Both of them were inhibited by L-NAC and diphenyleneiodoniumchloride. Conclusion Combination therapy with ATO and PTL has an augmented anticancer effect on pancreatic cancer. The mechanism is correlated with its ability to induce reactive oxygen species generation and apoptosis.%目的 研究三氧化二砷和小白菊内酯联合用药对人胰腺癌细胞的抗癌作用及其机制.方法 胎盘蓝拒染法检测细胞活力;利用AnnexinV和PI双染法检测细胞是否发生凋亡,利用DAPI染色法检测细胞核碎片化情况;应用流式细胞仪检测胰腺癌细胞PANC-1和BxPC-3的活性氧水平;应用Western blot技术检测血红素加氧酶的表达水平.结果 三氧化二砷和小白菊内酯联合用药对胰腺癌细胞具有生长抑制作用,并明显优于三氧化二砷或小白菊内酯单独用药.三氧化二砷和小白菊内酯处理细胞后能够诱导细胞凋亡,并增加活性氧的生成和提高血红素加氧酶的表达水平,上述作用均可被L-NAC和DPI所阻断.结论 三氧化二砷和小白菊内酯联合用药对胰腺癌细胞具有良好的抗癌作用,机制主要和增加活性氧的生成以及诱导凋亡相关.

  11. Arsenic cardiotoxicity: An overview.

    Science.gov (United States)

    Alamolhodaei, Nafiseh Sadat; Shirani, Kobra; Karimi, Gholamreza

    2015-11-01

    Arsenic, a naturally ubiquitous element, is found in foods and environment. Cardiac dysfunction is one of the major causes of morbidity and mortality in the world. Arsenic exposure is associated with various cardiopathologic effects including ischemia, arrhythmia and heart failure. Possible mechanisms of arsenic cardiotoxicity include oxidative stress, DNA fragmentation, apoptosis and functional changes of ion channels. Several evidences have shown that mitochondrial disruption, caspase activation, MAPK signaling and p53 are the pathways for arsenic induced apoptosis. Arsenic trioxide is an effective and potent antitumor agent used in patients with acute promyelocytic leukemia and produces dramatic remissions. As2O3 administration has major limitations such as T wave changes, QT prolongation and sudden death in humans. In this review, we discuss the underlying pathobiology of arsenic cardiotoxicity and provide information about cardiac health effects associated with some medicinal plants in arsenic toxicity.

  12. Efficacy analysis of amifostine combined with arsenic trioxide and vitamin C in the treatment of patients with high-risk myelodysplastic syndromes%氨磷汀联合三氧化二砷与维生素C治疗高危骨髓增生异常综合征的疗效分析

    Institute of Scientific and Technical Information of China (English)

    万鼎铭; 张媛; 张素平; 曹伟杰; 边志磊

    2013-01-01

    目的 观察氨磷汀联合三氧化二砷(As2O3)与维生素C治疗高危骨髓增生异常综合征的疗效.方法 15例患者应用氨磷汀500 mg/d,静脉滴注,As2O3 10 mg/d,静脉滴注,结束4h后应用维生素C2.0 g/d,静脉滴注,每周连续用药5d,间隔2d,4周为1个疗程.结果 完全缓解2例(13.3%),部分缓解3例(20.0%),血液学改善5例(33.3%),5例(33.3%)无效,总有效率为66.7%.结论 氨磷汀联合As2O3与维生素C治疗高危骨髓增生异常综合征疗效确切,且未见明显不良反应.%Objective To observe the efficacy of amifostine combined with arsenic trioxide and vitamin C on patients with high-risk myelodysplastic syndromes.Methods Fifteen patients received amifostine 500 mg/d,arsenic trioxide 10 mg/d by intravenous infusion and then recieved vitamin C 2.0 g/d by intravenous infusion after 4 hours,continuous medication for 5 days a week,interval 2 days,4 weeks repeated for a course.Results Complete remission in 2 cases (13.3%),partial remission in 3 cases (20.0%),hematologic improved in 5 cases(33.3%),invalid in 5 cases(33.3%),and the total effective rate was 66.7%.Conclusions Amifostine combined with arsenic trioxide and vitamin C is effective and has no significant adverse reactions in treating high-risk myelodysplastic syndromes.

  13. 三氧化二砷联合华蟾素治疗晚期肝癌的近期疗效分析%Arsenic trioxide joint element HuaChan recent curative effect analysis for the treatment of advanced liver cancer

    Institute of Scientific and Technical Information of China (English)

    毛雪梅

    2014-01-01

    Objective:To observe the analysis of arsenic trioxide in late in the treatment of liver cancer coalition HuaChan short-term curative ef ect.Methods:A retrospective analysis of clinical data of 56 patients with advanced liver cancer,according to the treatment time is divided into research group (28 cases)and control group (28 cases),two groups of patients were given conventional treatment,the team on the basis of the joint HuaChan element arsenic trioxide,two groups of patients in the near future curative ef ect observed.Result:The team objective ef iciently,clinical benefit rate and life quality imG provement were superior to control group,with statistical significance dif erence (P<0.05).Conclusion:On the basis of routine therapy for patients with advanced liver cancer arsenic trioxide joint HuaChan hormone treatment,can achieve good short-term curative ef ect,can ef ectively improve the clinical symptoms and quality of life,resistant to certain toxicity.%目的:观察分析在晚期肝癌治疗中三氧化二砷联合华蟾素的近期疗效.方法:回顾性分析56例晚期肝癌患者临床资料,按治疗时间分为研究组(28例)和对照组(28例),两组患者均给予常规治疗,研究组在此基础上加以三氧化二砷联合华蟾素,对比观察两组患者近期疗效.结果:研究组客观有效率、临床受益率、生活质量改善均优于对照组,具有统计学差异意义(P<0.05).结论:结论在常规治疗基础上给予晚期肝癌患者三氧化二砷联合华蟾素治疗,可取得良好的近期疗效,能有效改善患者临床症状和生活质量,可耐一定毒性.

  14. Anti-tumor Effects and Mechanism of Arsenic Trioxide in Combination with Sodium Citrate in Gastric Cancer Cells in vitro%柠檬酸钠联合三氧化二砷体外抗人胃癌细胞及其作用机制

    Institute of Scientific and Technical Information of China (English)

    郑步平; 张晓东; 陆云飞

    2012-01-01

    Objective To study the anti-tumor effects of citrate combined with arsenic trioxide on human gastric cancer cell in vitro and possible mechanism. Methods Citrate (final concentration of 5 mmol / L) and (or) different concentrations of As2O3 (final concentration was 5 or 10 μmol / L) treated in vitro cultured gastric cancer cell line SGC-7901 and BGC-803. Flow cytometry was used to detect apoptosis and cell cycle changes. The apoptosisrelated gene Bcl-2 and Mcl-1 expressions were identified by RT-PCR to observe. Results Citrate combining with As2 O3 had a stronger inhibition function on human gastric cancer cell line compared with citrate or As2O3 (P<0. 05) alone. Compared with blank group, the cell cycle distribution was arrested at G2/ M phase, and the proportion of G0/G1 phase cell decreased and G2/M phase increased (P<0. 05). The expression of bcl-2 and mcl-1 was significantly decreased(P<0. 05). Conclusion Citrate combining with As2O3 had the synergistic effects on gastric cancer cell. The mechanism might be related to cell cycle blocking and apoptosis-inducing effects through bcl-2 and mcl-1 genes.%目的 探讨柠檬酸钠(Citrate)与三氧化二砷(As2O3)联合应用对胃癌细胞的凋亡及其作用机制.方法 用Citrate(终浓度为5 mmol/L)和(或)不同浓度的As2O3(终浓度依次为5、10 μmol/L)处理体外传代培养的胃癌细胞株SGC-7901和BGC-803.流式细胞仪检测细胞凋亡和细胞周期的变化;RTPCR法观察凋亡相关基因Bcl-2、Mcl-1表达的变化.结果 Citrate与As2O3联合应用相对于单用Citrate或As2O3可显著提高诱导胃癌细胞凋亡率(P<0.05);与空白组相比,用药后G0/G1期细胞比例下降,G2/M期细胞比例上升,细胞周期阻滞于G2/M期,抗凋亡基因Bcl-2、Mcl-1表达明显下降.结论 Citrate与As2O3联合应用具有协同抗胃癌细胞的作用,其机制可能与细胞周期阻滞、增强诱导胃癌细胞凋亡以及调控凋亡相关基因的表达有关.

  15. Influence of arsenic trioxide on the growth activity and apoptosis of gastric cancer cell during hypoxia%三氧化二砷对低氧下人胃癌细胞SGC-7901生长活性及凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    王彬; 王树庆

    2009-01-01

    目的 探讨三氧化二砷(As2O3)在低氧条件下对体外培养的人胃癌细胞SGC-7901生长的抑制及凋亡影响.方法 用氯化钴(CoCl2)制作低氧模型, 设常氧组、低氧组、低氧加药物组,分别取0.5、1.0、2.0、5.0、10.0 μmol/L五个不同浓度的As2O3作用于胃癌细胞,用细胞活力测定(MTT)法检测药物作用后的细胞活力,HOECHST33258染色试剂盒测细胞凋亡.结果 ①低氧加药物组As2O3对SGC-7901 细胞生长有抑制作用,与常氧对照组比较差异有统计学意义(P<0.05),并呈剂量-时间-效应关系.②低氧加药物组中,随着As2O3浓度的升高,胃癌细胞凋亡率也逐渐升高(P<0.05).结论 低氧下As2O3对人胃癌细胞SGC-7901生长有抑制和诱导凋亡作用,这种作用可能是As2O3发挥抗肿瘤的生物学基础.%Objective To investigate the effect of arsenic trioxide (As2O3) on the inhibition and apoptosis of gastric cancer cell SGC-7901 during hypoxia. Methods The environment of hypoxia was established by CoCl2 method. The gastric cancer cell were divided into three groups:normal group, hypoxia group and hypoxia combined arsenic trioxide group. The gastric cancer cell SGC-7901was stimulated respectivly 0.5,1.0,2.0,5.0 μmol/L and 10.0 μmol/L of arsenic trioxide.The growth activity of the gastric caner cell of As2O3 was determined by MTT ,and the apoptosis of the gastric caner cell by arsenict rioxide were examined with HOECHST33258 of gastric cancer cell SGC-7901, there was a significant difference rate gradually increased with higher concentration of As2O3 in hypoxia combined arsenic trioxide groups(P<0.05). Conclusion The growth of human gastric cancer cell SGC-7901 were suppressed, and apoptosis of human gastric cancer cell SGC-7901were induced by As2O3 during hypoxia,it may be biological basic of anti-tumor of As2O3.

  16. 三氧化二砷联合华蟾素抗裸鼠人肝癌移植瘤血管新生的作用%Anti-angiogenesis Effect of Arsenic Trioxide plus Cinobufacin on Human Hepatocarcinoma Transplantation Model Nude Mice

    Institute of Scientific and Technical Information of China (English)

    刘琳; 陈宝安; 秦叔逵; 赵伟; 李苏宜; 邱少敏; 王南瑶

    2011-01-01

    Objective To study the anti-angiogenesis effect and toxicity of arsenic trioxide (As2O3) plus cinobufacin on transplanted human hepatocarcinoma in nude mice, and the acting mechanism of the treatment was explored as well. Methods Human hepatocarcinoma was transplanted in nude mouse, and the modeled mice were divided at random into 4 groups, 8 in each group. They were treated respectively with normal saline (GA), 2. 5 mg/kg As2O3 (GB), 5 mL/kg cinobufacin (GC) and 2.5 mg/kg As2O3 + 5 mL/kg cinobufacin (GD), by intraperitoneal injection for 21 days. The anti-tumor effects was evaluated by estimating general condition of nude mice, tumor size, microvessel density(MVD) level. Expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor(EGFR) in tumor, in tumor tissue of mice as well as pathology of tumor were detected by immunohistochemistry assay, optical microscope, transmission electron microscope ( TEM), respectively. Moreover, blood routine and pathological examinations of liver and kidney were performed.Results The tumor weight and volume were 0. 65 ± 0. 25 g and 0. 44 ± 0. 14 cm3 in GB, 0. 70 ± 0. 27 g and 0. 46 ±0. 19 cm3 in GC, 0.42 ±0. 16 g and 0. 26 ±0. 11 cm3 in GD, all significantly lower than those in GA (1.06 ±0. 25 g and 0. 67 ±0. 17 cm3, P<0. 05). The coefficient of drug interaction (CDI) on tumor weight was 0. 97 and that on tumor size was 0. 86, all less than 1, showing the synergistic action between the two drugs. Expressions of VEGF and EGFR in tumor as well as the MVD were decreased in GB and GC, and the decreasing of these indices were even more significant in GD. Pathologic examination showed the growth of tumor in GB, GC and GD were all inhibited significantly. No obvious toxicity of the treatments to the hepatic, renal and hematopoietic systems in the nude mice was observed. Conclusions As2O3 and cinobufacini showed synergistic action in inhibiting human hepatocarcinoma in nude mice and the

  17. Arsenic trioxide enhances the therapeutic efficacy of adjuvant post-operative chemotherapy of gastric carcinoma while protecting bone marrow%三氧化二砷改善胃癌患者术后辅助化疗疗效同时减轻骨髓抑制

    Institute of Scientific and Technical Information of China (English)

    Hong Sui; Yuxian Bai; Yu Han; Kaibing Wang

    2009-01-01

    Objective: The aim of the study was to investigate the prospective study if treatment with arsenic trioxide (As2O3) could enhance disease-free survival as adjuvant post-operative chemotherapy for gastric cancer patients and protect bone marrow from the negative effects of chemotherapy. Methods: 84 adults were randomized into two groups. Patients in treat- ment group were treated with As203 and FOLFOX regimen, the other were administered with FOLFOX regimen only. Results: Four patients were withdrawn in treatment group after 3-4 cycles and the reasons were headache and fidgety (n = 2), ar- rhythmia (n = 1) and AST/ALT elevation (n = 1), while 1 patient in control group after 4 cycles for neutropenia. In the treatment group, the median DFS was 28.34 months (95% CI, 25-33 months). While in control group, the median DFS was 24.50 months (95% CI, 20-30 months). This difference was not statistically significant (chi-square: 2.8885; P value: 0.0892). Pa- tients in the same subgroup of node-positive was 29 in the treatment group and 32 in control group, respectively. The median DFS was 27.87 months (95% CI, 25-31 months) in the treatment group and 24.18 months (95% CI, 19-31 months) in the control group with promising statistical significance (HR 1.89; chi-square: 4.78; P value: 0.0287). The most common grades 3-4 toxicity was leucopenia (n = 11) in control group and the difference was significant (chi-square: 3.9768, P value: 0.046) compared with that in treatment group (n = 4). Conclusion: The combination of arsenic trioxide and FOLFOX regimen has a potential advantage of enhancing disease-free survival in patients with gastric cancer in nodal-positive status as post-opera- tive chemotherapy, and protect bone marrow from the negative effects of chemotherapy.

  18. The curative effect with the combination therapy of Arsenic Trioxide and Ascorbic Acid in relapsed and refractory multiple myeloma%亚砷酸联合维生素C治疗复发难治性多发性骨髓瘤的疗效观察

    Institute of Scientific and Technical Information of China (English)

    王祥民; 张姣丽; 季国; 石培民

    2014-01-01

    Objective To investigate the curative effect with the combination therapy of Arsenic Trioxide and Ascorbic Acid in relapsed and refractory multiple myeloma. Methods 42 patients of relapsed and refractory multiple myeloma hospitalized during 2008 and 2011 were enrolled, and randomly divided into two groups: arsenic trioxide intervention group(control group)and arsenic trioxide combine with ascorbic acid intervention group(combination group), with each group 21 patients. The control group were given arsenic trioxide 10 mg/d intrave-nously daily. Each cycle was 6 weeks in duration, comprising 4 weeks of therapy followed by 2 weeks of intermission;while the combination group received ascorbic acid 1.0 g/d intravenously daily during the treatment time of arsenic trioxide in addition to the treatment of the control group. All patients received thalidomide 100 mg/d orally during the treatment intermission. Results (1) The combination group's overall response was 63%, which was much higher than the control group(29%)(P=0.043). (2) Kaplan-Meier statistical analysis showed that the median progression-free survival of the combination group was 9.0 months(range 6.2-11.8 months), which was longer than the control group(P=0.043). The median overall survival of the combination group was 14.0 months(range 11.4-16.6 months), which was also longer than the control group(P=0.038). (3) No significant difference was found between the two groups when referred to the adverse events(P>0.05). Conclusion Compared with the control group, the combination therapy of arsenic Trioxide and ascorbic acid acquired better curative effect in relapsed and refractory multiple myeloma patients.%目的:探讨亚砷酸联合维生素 C 对复发难治性多发性骨髓瘤的疗效,并与单用亚砷酸治疗进行比较。方法将2008至2011年收治的42例复发难治性多发性骨髓瘤患者随机分为两组:单用亚砷酸组(对照组)、亚砷酸联合维生素 C 组

  19. Patent Information Analysis of Arsenic Trioxide in Medical Application%三氧化二砷在医药领域中应用的专利信息分析

    Institute of Scientific and Technical Information of China (English)

    邢爽; 刘兰茹; 岳鹏; 刘培伟

    2016-01-01

    目的:系统分析在中国申请的三氧化二砷应用于医药领域的专利信息。方法利用国家知识产权局专利检索与服务系统和Soopat专利搜索引擎,检索在我国申请并公开的三氧化二砷在医药领域中应用的发明专利,并从其专利申请数量、区域分布数量、主要申请人、法律状态、技术动向等方面进行定量分析和定性分析。结果三氧化二砷在医药领域的专利申请量总体上呈增长趋势,2001年后增长趋势显著;国内专利申请人所在区域主要集中在北方及浙江沿海一带;国内申请量远高于国外在中国的申请量,国外申请量仅为4.44%,但国内专利申请主要集中在中药和药物制剂,国外则均为化合物;职务专利占申请总量的43.70%,申请人主要为大学(研究所)、公司、医院。结论我国在三氧化二砷的医药应用研究已有一定基础,但专利的维护和成果转化率不高;三氧化二砷对多种疾病的治疗具有应用价值,尤其具有广泛的抗瘤谱,故三氧化二砷在医药领域的专利申请仍具有较大上升空间。%Objective To systematical analyzes the patent information of arsenic trioxide ( As2O3 ) applied in Chinese medicine. Methods The State Intellectual Property Office patent search and service systems and Soopat patent search engine were used to search the patent application of As2O3 in the medical field in China,and its number of patent applications,the number of regional distribution,the princi-pal applicant,legal status,technology trends were analyzed in quantitative and qualitative way. Results As2O3 patent applications in the field of medicine enjoyed an overall growth,with a significant growth trend after 2001;the domestic patent applicants were mainly con-centrated in the northern area and the coastal areas of Zhejiang;the domestic applications were much more than international applica-tions(only 4. 44%),but the domestic

  20. 三氧化二砷对体外培养大鼠软骨细胞增殖和凋亡的影响%Effects of arsenic trioxide on rat primary chondrocytes in vitro

    Institute of Scientific and Technical Information of China (English)

    王娇; 崔洋; 刘伟东; 孟红梅

    2013-01-01

    Objective To study the cell viability,proliferation and apoptosis of cultured rat primary chondrocytes exposed to different doses of arsenic trioxide (As2O3) in vitro.Methods The third generation of primary cultured chondrocytes were treated with As2O3 at 0.5,1.0,2.0,4.0 and 8.0 μmol/L for 24,48 and 72 h.The cell vitality was detected with Cell Counting Kits-8 and the proliferation and apoptosis of chondrocytes were detected by flow cytometry.Results Compared to the control group,the vitality of chondrocytes exposed to each concentrations of As2O3 was inhibited (except the group at 0.5 μmnol/L for 24 h).Both of the distribution of cell cycle and the rate of apoptosis of chondrocytes analyzed by flow cytometry showed that As2O3 induced G2 cell-cycle arrest and increased apoptotic rate.Conclusion As2O3 could inhibit the proliferation and promote the apoptosis of rat primary chondrocytes in vitro.%目的 探讨三氧化二砷(As2O3)对体外培养大鼠软骨细胞活力、增殖和凋亡的影响.方法 采用细胞培养的方法,原代培养1~3天Wistar大鼠的关节软骨细胞,取第3代细胞进行实验,按染砷剂量不同分为0(对照)、0.5、1.0、2.0、4.0、8.0 μmol/L组.采用细胞增殖与毒性检测方法(CCK-8法),在染砷24、48、72 h测定细胞活力变化;流式细胞仪检测砷对软骨细胞周期及凋亡的影响.结果 与对照组相比,各浓度染砷大鼠软骨细胞(除0.5 μmol/L 24 h无统计学意义)活力均被抑制(P<0.01);流式细胞仪分析结果显示,As2O3将大鼠软骨细胞周期阻滞于G2期(P<0.05),使细胞凋亡率明显增加(P<0.05).结论 As2O3可以抑制体外培养大鼠软骨细胞的增殖,促进细胞凋亡.

  1. Efficacy of Arsenic Trioxide combined with GDP regimen for patients with aggressive relapsed or refractory non-Hodgkin's lymphoma%亚砷酸联合GDP方案治疗难治性或复发性非霍奇金淋巴瘤的疗效观察

    Institute of Scientific and Technical Information of China (English)

    丁富强; 乔红梅; 李晓霞; 李恩孝

    2011-01-01

    目的:观察亚砷酸(三氧化二砷,As2O3)联合GDP方案(吉西他滨,顺铂,地塞米松)治疗难治性或复发性非霍奇金淋巴瘤(non-hodgkin's lymphoma,NHL)的有效率.方法:23例难治性或复发性非霍奇金淋巴瘤(NHL),给予吉西他滨1000mg/m2,第1和第8天,顺铂25mg/m2 第1-3天,地塞米松 20mg/m2,第1-5天,As2O310mg/d,第1-14天.21天为1个周期.结果:完全缓解9例,部分缓解6例,总有效率65.22%.肿瘤中位进展时间6个月,1年生存率39.13%.不良反应主要为血液学毒性.结论:亚砷酸联合GDP方案是治疗难治性或复发性非霍奇金淋巴瘤较为安全有效的化疗方案.%Objective:To evaluate the efficacy and safety of chemotherapy regimen with arsenic trioxide ( As2 O3 )combined with GDP ( gemcitabine, cisplatin and dexamethasone ) for patients with aggressive relapsed or refractory NHL. Methods: All 23 patients with relapsed or refractory NHL were observed,23 patients were treated by gemcitabine 1000 mg/m2 on d1 ,8, cisplatin 25 mg/m2 on d1-3 and dexamethasone 25 mg/m2 on d1-5, Arsenic oxide 10mg/d on d1-14。 21 days for a cycle. Results: Of experimental group all response rate was 65.22% ,including 9 complete response and 6 partial response. Median time to progression was 6 months, and 1 year survival rate was 39.13%.The major adverse reaction was toxicity of bone marrow. Conclusion: Arsenic trioxide combined with GDP regimen is effective and safe for patients with aggressive relapsed or refractory non - Hodgkin's lymphoma.

  2. Preliminary Examination of Intra-articular Injection Arsenic Trioxide for Treatment of Collagen-induced Arthritis in Rats%关节腔内注射三氧化二砷治疗胶原诱导的大鼠关节炎的初步观察

    Institute of Scientific and Technical Information of China (English)

    刘红; 高锦团; 李拾林

    2011-01-01

    Objective To investigate the feasibility and effectiveness of intra-articular arsenic trioxide injection for treatment of rat collagen-induced arthritis. Methods Adult female Wistar rats were used to induce CIA and the rats were divided into two groups : control group and treat group. Their ankle joints were injected with 0.1 mL PBS and 10% arsenic trioxide respectively, once every three days, a total of four times. Then they were killed three days after the last injection. The treated ankles were assessed included arthritis index, ankle circumference, synovial thickness by high frequency ultrasound, radiographically and histologically before and after intra-articular injection. Results The CIA rats had some difficulty in walking and then were cured. Compared with the control group,the rats of the treat group had lower articular index (P<0.01) , ankle joint swelling(P<0.05) , synovial membrane ( P<0.05) ,and slighter bone destruction from X rays, pathological changes. Conclusions Intra-articular injection arsenic trioxide can relieve joint swell and repress synovitis.%目的 探讨关节腔内注射三氧化二砷(ATO)治疗胶原诱导的关节炎(CIA)的可行性及疗效.方法 成年雌性Wistar大鼠建立CIA动物模型.将成功造模的大鼠分成对照组和治疗组,分别于踝关节腔内注射PBS溶液和10% ATO溶液各0.1 mL,每3 d 1次,共4次,末次注射3 d后取材.2组分别于注射前及注射后进行关节炎指数评分,计算踝关节环径,并应用高频超声观察踝关节,测量滑膜厚度以及放射学X线及病理学观察.结果 关节炎诱导成功后大鼠出现行动不便.治疗组与对照组比较,关节炎指数评分降低(P<0.01)、踝关节肿胀下降(P<0.05)、滑膜厚度变薄(P<0.05);治疗组踝关节X线示关节破坏减少,病理改变亦减轻.结论 关节腔内注射ATO可以缓解关节肿胀,抑制滑膜炎.

  3. 三氧化二砷诱导人鼻咽低分化鳞癌BALB/C裸鼠移植瘤的细胞分化和凋亡的研究%Arsenic Trioxide Induced Differentiation and Apoptosis in Human Nasopharyngeal Carcinoma Xenografts in BALB/C Nude Mice

    Institute of Scientific and Technical Information of China (English)

    郑毓武; ZHENG Yuwu; 杜彩文; DU Caiwen; 李德锐; LI Derui; LIN Yingcheng; WU Mingyao

    2004-01-01

    Objective: To study the effect of arsenic trioxide (As2O3) on human poorly differentiated nasopharyngeal cancer cell line, CSNE-1, in vivo and its possible mechanism of action. Methods: CSNE-1ceils were established as xenografts in BALB/C nude mice. The tumor-bearing mice were treated with As2O3 at the dose of 5 mg/kg every day. The tumor growth was observed by tumor-growth curve. Morphologic changes were studied under light microscopy and electron microscopy. TUNEL was used to detect apoptosis. The expression of PCNA, p53, Bcl-2 and Bax were determined by immunohistochemistry. Results: The cell growth and proliferate activity were significantly inhibited by As2O3 at the dose of 5 mg/kg every day. Morphologic changes such as the formation of keratinization of tumor cells, decreased ratio of nuclear/cytoplasm, increased organelle and plasmic fibril in cytoplasm were identified. Cytodesma, desmosomes and micro-process were seen under light microscopy and transmission electron microscopy, which revealed that the cancer cells underwent differentiation. In addition, remarkable cell apoptosis were observed by TUNEL assay. Over expression of p53 and Bax was detected in the As2O3 treatment group when compared with control group. Conclusion: As2O3 inhibited proliferation of human poorly differentiated nasopharyngeal cancer cell CSNE-1 by inducing differentiation and apoptosis, which may be related to the up-regulation of p53 and Bax expression.

  4. 三氧化二砷逆转人胃癌细胞SGC7901/ADR耐药性的作用机制%Reversal mechanism of arsenic trioxide in the drug resistance of human gastric cancer cell line SGC7901/ADR

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To investigate the reversal effect of arsenic trioxide (As2O3) on the multidrug resistance of human gastric tumor SGC7901/ADR cell line to adriamycin (ADM) and its reversal mechanisms. Methods: The non-cytotoxic concentration of As2O3 and the sensitivity of SGC7901/ADR cells to ADM were detected by MTT assay. The drug concentration and P-gp function of SGC7901/ADR cells were measured with flow cytometry (FCM), and the impacts of As2O3 on the GST-π and TopoⅡ expressions of SGC7901/ADR cells were analyzed by immunohistochemical method. Results: As2O3 at 0.4 to 0.8 μmol/Lconcentrations were not significantly cytotoxic to SGC7901/ADR cells. As2O3 at 0.8 μmol/L could improve the sensitivity of SGC7901/ADR cells to ADM via inhibiting P-gp function, down-regulating GST-π expression and increasing the intracellular accumulation of ADM in SGC7901/ADR cells. Conclusion: As2O3 can reverse partly the drug-resistance of SGC7901/ADR cells to ADM, which may be related with inhibiting the P-gp function and down-regulating GST-π expression.

  5. Industrial contributions of arsenic to the environment.

    Science.gov (United States)

    Nelson, K W

    1977-08-01

    Arsenic is present in all copper, lead, and zinc sulfide ores and is carried along with those metals in the mining, milling and concentrating process. Separation, final concentration and refining of by-product arsenic as the trioxide is achieved at smelters. Arsenic is the essential consistent element of many compounds important and widely used in agriculture and wood preservation. Lesser amounts are used in metal alloys, glass-making, and feed additives. There is no significant recycling. Current levels of arsenic emissions to the atmosphere from smelters and power plants and ambient air concentrations are given as data of greatest environmental interest. PMID:908308

  6. Acute and chronic arsenic toxicity.

    Science.gov (United States)

    Ratnaike, R N

    2003-07-01

    Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs. There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven. The focus of management is to reduce arsenic ingestion from drinking water and there is increasing emphasis on using alternative supplies of water.

  7. Resistance to Arsenic- and Antimony-Based Drugs

    OpenAIRE

    Milena Salerno; Arlette Garnier-Suillerot

    2003-01-01

    Organic arsenicals were the first antimicrobial agents specifically synthesized for the treatment of infectious diseases such as syphilis and sleeping sickness. For the treatment of diseases caused by trypanosomatid parasites, organic derivatives of arsenic and the related metalloid antimony are still the drugs of choice. Arsenic trioxide, As203, has been used for a long time in traditional Chinese medicines for treatment of various diseases, and it has recently been shown to be clinically ac...

  8. Tracking the transformation and transport of arsenic sulfide pigments in paints : synchrotron-based X-ray micro-analyses

    NARCIS (Netherlands)

    Keune, Katrien; Mass, Jennifer; Meirer, Florian; Pottasch, Carol; van Loon, Annelies; Hull, Alyssa; Church, Jonathan; Pouyet, Emeline; Cotte, Marine; Mehta, Apurva

    2015-01-01

    Realgar and orpiment, arsenic sulfide pigments used in historic paints, degrade under the influence of light, resulting in transparent, whitish, friable and/or crumbling paints. So far, para-realgar and arsenic trioxide have been identified as the main oxidation products of arsenic sulfide pigments.

  9. Tracking the transformation and transport of arsenic sulfide pigments in paints: synchrotron-based X-ray micro-analyses

    NARCIS (Netherlands)

    K. Keune; J. Mass; F. Meirer; C. Pottasch; A. van Loon; A. Hull; J. Church; E. Pouyet; M. Cotte; A. Mehta

    2015-01-01

    Realgar and orpiment, arsenic sulfide pigments used in historic paints, degrade under the influence of light, resulting in transparent, whitish, friable and/or crumbling paints. So far, para-realgar and arsenic trioxide have been identified as the main oxidation products of arsenic sulfide pigments.

  10. A biography of arsenic and medicine in Hong Kong and China.

    Science.gov (United States)

    Au, W Y

    2011-12-01

    Arsenic trioxide has been used in traditional Chinese medicine for over 5000 years, but lost its appeal due to its toxicity. It was rediscovered in western medicine and enjoyed a renaissance from 1830 to 1930, as the first effective chemotherapy against syphilis, parasites and leukaemia. These years were also a time of political turmoil in China. The Nanking treaty (29 August 1842) turned Hong Kong into a colony, while the Xinhai Revolution (10 October 1911) gave birth to a republic of China. Arsenic returned to China and Hong Kong with the establishment of the first medical schools from 1887 to 1920. Until 1950, oral arsenic trioxide was the standard anti-leukaemic treatment in Queen Mary Hospital. The advent of alkylating chemotherapeutic agents replaced arsenic trioxide in Hong Kong and around the world. In the 1970s, however, the specific activity of arsenic trioxide against acute promyelocytic leukaemia was re-discovered during the Cultural Revolution in Harbin, China. In 1997, Hong Kong was returned to China. In the same year, arsenic trioxide returned to the world stage. Intravenous arsenic trioxide became the worldwide standard therapy for relapsed acute promyelocytic leukaemia. Oral administration of arsenic trioxide was revived in Hong Kong in 2000. This resulted in the first locally produced, registered, patented prescription drug in Hong Kong. Pending imminent manufacture, this product is poised to revolutionise acute promyelocytic leukaemia care and may hold the key to saving the lives of acute promyelocytic leukaemia patients worldwide. The remarkable journey of arsenic in the setting of medical history of China and Hong Kong is reviewed. PMID:22147326

  11. A biography of arsenic and medicine in Hong Kong and China.

    Science.gov (United States)

    Au, W Y

    2011-12-01

    Arsenic trioxide has been used in traditional Chinese medicine for over 5000 years, but lost its appeal due to its toxicity. It was rediscovered in western medicine and enjoyed a renaissance from 1830 to 1930, as the first effective chemotherapy against syphilis, parasites and leukaemia. These years were also a time of political turmoil in China. The Nanking treaty (29 August 1842) turned Hong Kong into a colony, while the Xinhai Revolution (10 October 1911) gave birth to a republic of China. Arsenic returned to China and Hong Kong with the establishment of the first medical schools from 1887 to 1920. Until 1950, oral arsenic trioxide was the standard anti-leukaemic treatment in Queen Mary Hospital. The advent of alkylating chemotherapeutic agents replaced arsenic trioxide in Hong Kong and around the world. In the 1970s, however, the specific activity of arsenic trioxide against acute promyelocytic leukaemia was re-discovered during the Cultural Revolution in Harbin, China. In 1997, Hong Kong was returned to China. In the same year, arsenic trioxide returned to the world stage. Intravenous arsenic trioxide became the worldwide standard therapy for relapsed acute promyelocytic leukaemia. Oral administration of arsenic trioxide was revived in Hong Kong in 2000. This resulted in the first locally produced, registered, patented prescription drug in Hong Kong. Pending imminent manufacture, this product is poised to revolutionise acute promyelocytic leukaemia care and may hold the key to saving the lives of acute promyelocytic leukaemia patients worldwide. The remarkable journey of arsenic in the setting of medical history of China and Hong Kong is reviewed.

  12. Effects of Fas in combined treatment of TRAIL and arsenic trioxide-induced apoptosis in human gastric cancer cells%死亡受体Fas在TRAIL联合三氧化二砷诱导人胃癌细胞凋亡中的作用

    Institute of Scientific and Technical Information of China (English)

    段晓秋; 王晶; 申维喜; 杨宇

    2012-01-01

    OBJECTIVE: To study the effects of Fas in combined treatment of TRAIL(tumor necrosis factor-related apoptosis-inducing ligand) and arsenic trioxide(As2O3)-induced apoptosis in human gastric cancer SGC-7901 cells. METHODS: SGC-7901 cells were cultured in vitro, Sense and Antisense SGC-7901 cells were obtained from transfection of sense and antisense oligo nucleic acid, respectively. Untransfected, Sense and Antisense cells were treated with 0.5 μ g/ml As2O3+0.2 μ g/ml TRAIL, respectively. Cell proliferation was evaluated by MTT assay after 24, 48 and 72 h; cell colony morphologies were examined under inverted microscope after 48 h; apoptosis rate measured by DAPI staining and flow cytometer; and Fas, FADD and Parp expression determined by Western blot. RESULTS: Treatment by Fas antisense oligo nucleic acid transfection decreased the number of dead cells as detected by microscopy, exerted cell growth inhibition and As2O3+TRAIL-induced apoptosis effects. The expressions of Fas, FADD and activated Parp were all down-regulated (P<0.05). CONCLUSION: Fas signaling pathway may be important in the process of SGC-7901 apoptosis induced by combined treatment of As2O3 and TRAIL.%目的:探讨Fas在肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand,TRAIL)与三氧化二砷(arsenic trioxide,As2O3)联合诱导人胃癌细胞凋亡过程中的作用.方法:采用体外培养人低分化胃腺癌细胞SGC-7901,分别以Fas正义、反义寡核苷酸转染SGC-7901细胞获得Sense、Antisense细胞.以0.5μg/ml As2O3+0.2μg/ml TRAIL分别处理未转染细胞、Sense组细胞以及Antisense组细胞,采用MTT法检测24、48、72 h后细胞增殖情况;倒置显微镜观察联合作用48 h后细胞集落形态;DAPI染色法、流式细胞仪技术检测48 h时细胞凋亡率;Western blot法检测48 h细胞中Fas、FADD以及Parp表达情况.结果:与未转染组和Sense组细胞比较,转染Fas反义

  13. Treatment of relapsed or refractory multiple myeloma by arsenic trioxide and Thalidomide、ascorbic acid%亚砷酸联合反应停、维生素C治疗难治性复发性多发性骨髓瘤

    Institute of Scientific and Technical Information of China (English)

    郭子文; 许晓军; 周云香; 林淑华

    2014-01-01

    目的:观察亚砷酸(ATO)联合反应停、维生素C (VitC)治疗难治性复发性多发性骨髓瘤(MM)的疗效及安全性。方法:19例难治复发MM患者,应用亚砷酸(10mg/d)联合反应停(200~300mg/d)、VitC(2g/d),连用4周。结果:部分缓解(PR)47%,疾病稳定(SD)32%,疾病进展(PD)21%。主要不良反应为白细胞减少、消化道反应及肝功能损害。结论:ATO联合反应停、VitC治疗难治性复发性MM有效率较高,且毒副反应低,很有临床应用前景。%Objective: To observe the efficacy and side effects of arsenic trioxide(ATO) and Thalidomide、ascorbic acid(VitC)in the treatment of relapsed or refractory multiple myeloma (MM). Methods: patients with relapsed or refractory MM were treated by ATO(10 mg/d)and Thalidomide(200~300 mg/d) 、VitC(2g/d) lasting 4 weeks.Results: The partial remission(PR) rate was 47%. The stable disease(SD) rate was 32% and the progressive disease(PD) rate was 21%. The main side effects were leukocytopenia, digestive tract reaction and liver function damage. Conclusion: The regiment(ATO+ Thalidomide+ VitC) is effective and low adverse reaction for the treatment of relapsed or refractory MM.It has a prospect of clinical application.

  14. AMELIORATION OF GENOTOXICITY BY PAPAYA EXTRACT INDUCED BY ARSENIC CONTAMINATED DRINKING WATER

    Directory of Open Access Journals (Sweden)

    DHARMSHILA KUMARI

    2013-01-01

    Full Text Available Arsenic is an established genotoxic carcinogen in human. Arsenic trioxide (0.04mg/animal when administeredorally daily to albino swiss mice for 15 continuous days, increased the incidence of abnormalities to 30.6% inmeiotic metaphase chromosome, 5.88% in the gross morphology of sperm head and decreased the sperm countper unit volume of caput epididymal suspension to 64.16 in comparison to the control. The concurrent treatmentof papaya fruit extract and arsenic trioxide significantly decreased the abnormalities to19.6% in meioticchromosome, 4.16% in the sperm head morphology and increased the mean count of sperm to 82.28. Theincrease in abnormality of meiotic chromosome as well as abnormality in gross morphology of the sperm headand decrease in sperm count, as observed upon arsenic trioxide treatment, were ameliorated by the aqueouspapaya fruit extract. Therefore, it is suggested that the papaya fruit extract may reduce the risk of arsenic-inducedgenotoxicity.

  15. 三氧化二砷对肿瘤血管内皮细胞增殖、迁移、血管形成及其凋亡的影响%Arsenic Trioxide Impacted on Tumor Vascular Endothelial Cell Proliferation,Migration, Angiogenesis and Apoptosis

    Institute of Scientific and Technical Information of China (English)

    傅文达; 王雪雯; 张建华

    2011-01-01

    为了探讨三氧化二砷(As2O3)对肿瘤血管内皮细胞增殖、迁移、血管形成及其凋亡的机制,采用肝癌HepG2细胞上清诱导人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC)成为肿瘤血管内皮细胞(tumor-derived endothelial cells,Td-EC),通过细胞迁移、流式细胞术、血管形成实验检测Asz()3对HUVEC与Td-EC增殖、迁移、血管形成及其凋亡的影响.结果显示,在同样条件下与HUVEC相比,As(3在体外抑制Td-EC增殖、迁移和血管的形成及其促进凋亡的作用显著.结论:As2O3在体外可特异地抑制Td-EC增殖、迁移、血管形成及其凋亡.%To study the mechanism of arsenic trioxide (As2O3) on tumor vascular endothelial cell proliferation, migration, angio-genesis and apoptosis,the cells differentiated into tumor-derived endothelial cells (Td-Ecs) by co-culturing with supernatants of HepG2 cells,the anti-effect of As2O3 on Td-Ecs and HUVEC was detected with cell migration, flow cytometry,blood vessel formation assay. The results showed that As2O3 effected on Td-EC in vitro promote apoptosis, and inhibited their migration and blood vessel formation, was more significant than under the same conditions over HUVEC. Conclusion is that As2O3 in vitro specifically inhibit Td-EC proliferation,migration,angiogenesis and promote apoptosis.

  16. Impact of Arsenic Trioxide on Proliferation and Metastasis of Drug-Resistant Human Ovarian Carcinoma Cell Line%三氧化二砷对人卵巢癌耐药细胞株细胞增殖和转移能力的影响

    Institute of Scientific and Technical Information of China (English)

    黄守国; 孔北华; 马玉燕; 江森

    2002-01-01

    背景与目的:卵巢恶性肿瘤细胞对顺铂的耐药性及早期发生转移严重影响着卵巢恶性肿瘤患者的化疗效果.本研究探讨三氧化二砷(arsenic trioxide,As2O3)对人卵巢癌耐药细胞株3AO/cDDP细胞增殖和转移能力的影响及其机制.方法:采用四甲基偶氮唑蓝(MTT)法检测不同浓度As2O3对3AO/cDDP细胞的生长抑制率;采用流式细胞技术(FCM)检测As2O3对细胞凋亡率、细胞周期以及Fas、N-myc基因和nm23H1、MTA1基因表达的影响.所有结果均与对照组比较.采用透射电镜技术观察As2O3作用后3AO/cDDP细胞的形态变化.结果:As2O3明显抑制3AO/cDDP细胞的增殖,抑制作用呈时间和剂量依赖性(P005);形态学观察可看到As2O3作用后3AO/cDDP形成典型的凋亡小体.结论:As2O3通过上调Fas、nm23H1和下调N-myc、MTA1基因的表达,有效地降低人卵巢癌耐药细胞株细胞的增殖和转移能力.

  17. The revival of the ancient drug-arsenic

    Institute of Scientific and Technical Information of China (English)

    黄晓军

    2003-01-01

    Arsenic, a natural substance, has been used as a traditional Chinese medicine for more than a thousand years. However, this medicine fell into disuse in the 1930s following the advent of radiotherapy and conventional cytotoxic drugs and reports about arsenic poisoning from its long-term low-dose ingestion. Until the late 1970s, it had its rebirth when a series of research papers from China described the successful application of AiLing-1,1 a traditional Chinese compound, containing arsenic trioxide (ATO) and other ingredients. Research into the molecular mechanisms of arsenic action has furthered clinical application of this drug.

  18. Mechanisms of Arsenic Trioxide on Invasion and Adhesion of Human Breast Cancer Xenograft Tumor in Nude Mice%三氧化二砷影响人乳腺癌裸鼠移植瘤侵袭性和黏附性 Syk 机制

    Institute of Scientific and Technical Information of China (English)

    周艳; 吴振村; 程健君

    2015-01-01

    目的:探讨三氧化二砷(arsenic trioxide, AS2 O3)影响人乳腺癌裸鼠移植瘤侵袭性和黏附性 Syk作用机制。方法成功建立人乳腺癌裸鼠移植瘤模型,随机分为实验组(AS2 O3)和对照组(生理盐水)。7 d后观察肿瘤体积的变化,流式细胞术检测肿瘤组织细胞凋亡情况及两组荷瘤裸鼠肿瘤组织中基质金属蛋白酶-9(MMP-9)和细胞间黏附分子-1(ICAM-1)的表达情况。结果实验组荷瘤裸鼠肿瘤体积明显低于对照组,差异有统计学意义;实验组荷瘤裸鼠肿瘤组织细胞凋亡率明显高于对照组(P <0.01);实验组 ICAM-1表达明显高于对照组(P <0.05);实验组 MMP-9表达低于对照组(P <0.05)。结论AS2 O3对人乳腺癌裸鼠移植瘤具有明显的抑瘤作用,可降低肿瘤组织侵袭性增加其黏附性,其作用机制可能与蛋白酪氨酸激酶 Syk 的表达有关。%Objective To explore the mechanisms of arsenic trioxide (As2 O3 )on invasion and adhe-sion of human breast cancer xenograft tumor in nude mice.Methods Xenografted breast carcinoma in nude mice was established and the mice models were divided randomly into two groups,namely experi-mental (treated with AS2 O3 )and control group (treated with saline).After 7 days,the changes in xen-ograft tumor volume were measured,and the apoptosis of tumor cells were detected by flow cytometry. The expression of matrix metalloproteinase-9 (MMP-9)and intercellular adhesion molecular-1 (ICAM-1) were also detected using flow cytometry.Results The tumor volume of experimental group was signifi-cantly reduced compared with that of control group;while the tumor cell apoptosis of experimental group was higher than that of control group (P < 0.01 );Experimental group showed significantly increased ICAM-1 expression (P <0.05)and reduced MMP-9 expression (P <0.05)compared with control group. Conclusion As2 O3 could inhibit the growth of human breast cancer in

  19. 三氧化二砷对食管癌细胞株Eca109的放射增敏作用及机制%Radiosensitivity and Its Mechanism of Arsenic Trioxide on Esophageal Cancer Cell Line-Eca109

    Institute of Scientific and Technical Information of China (English)

    景绍武; 王雅棣; 吴凤鹏; 卢付河; 韩春; 刘青; 程云杰

    2011-01-01

    Objective To explore the effects of Arsenic trioxide (As2O3) and As2O3 combined with radiation on the growth inhibition of esophageal cancer cell line-Eca109. To analysis the impact of As2 O3 combined with radiation on the cell cycle and apoptosis in order to provide a theoretical basis for As2 O3 applied the treatment of esophageal cancer. Methods The inhibitory effects of radiation or/and As2O3 on proliferation were measured by MTT assay. The straight of irradiated group, As2 O3 group and combined group were fitted by linear correlation and linear regression and then sensitizing enhancement ratio (SER) was calculated. The change of cell cycle distribution and apoptosis were assayed by flow cytometry. The effects of As2 O3 combined with radiation on manganese superoxide dismutase (MnSOD) and cytochrome C (cyt-C) expression were measured by Western blot. Results With a clear dose and time effect, As2O3 could inhibit the proliferation of esophageal cell line-Eca109; As2 O3 definitely enhanced radiosensitivity of Eca109 cells. Flow cytometry analysis results indicated that G2/M phase proportion and apoptosis rate increased obviously after the effect of As2O3 and radiation. The expression of MnSOD was down-regulated, while cyt-C had no obvious change. Conclusion As2O3 could enhance radiation's killing effect on Eca1 09 cells through G2/M phase arrest, down-regulation of MnSOD and induction of apoptosis.%目的 探讨三氧化二砷(Arsenic trioxide,As2O3)及As2O3与放射线联合对食管癌Eca109细胞的增殖抑制作用;分析二者联合对Eca109细胞周期和凋亡的影响,为As2O3的临床应用提供理论依据.方法 MTT法观察放射线及As2O3单独及二者联合对食管癌Eca109细胞的增殖抑制作用,利用直线相关及直线回归拟合出照射组、As2O3组及联合组的直线,计算增敏比(sensitizing enhancement ratio,SER);流式细胞术检测As2O3联合放射线对Eca109细胞周期和凋亡的影响;Western blot

  20. Study on anti-tumor effect of arsenic trioxide on orthotopic breast cancer in mice by the optical in vivo imaging technology%应用活体成像技术对三氧化二砷抗小鼠4T1乳腺癌作用的研究

    Institute of Scientific and Technical Information of China (English)

    范临兰; 席晓霞; 魏虎来; 张强弩; 高飞云

    2013-01-01

    To study the proliferation-inhibiting action of arsenic trioxide( As2O3 ) on murine breast cancer 4T1 cells in vivo and in vitro with the optical in vivo imaging,and the advantages of the optical in vivo imaging technology were compared with the conventional animal experimental methods. The firefly lu-ciferase gene- transferred 4T1 breast cancer cells(4Tl-Luc cells) were used as target cells. The cellular cell proliferation was detected with both MTT colorimetric assay and bioluminescence(BLM) assay, and the morphological observation and AnnexinV and propidium iodide(Annexin V/PI) double-labeling were employed to assess the cell apoptosis in vitro. The 4T1-Luc cells were implanted orthotopically into the mammary fat pad of female BALB/c mice to establish the orthotopic breast cancer model, the tumor-bearing mice were treated with 5 mg/(kg · d) and 10 mg/(kg · d) As2O3 by introperitoneal injection once a day for 20 days,respectively,the optical in vivo imaging system was used to continuously and dynamically monitor the tumor growth. At the end of the treatment,the animals were killed,and the tumor tissue was removed and weighed. The tumor tissue sections were prepared with HE staining and CD34 immunocytochemistry staining to examine karyokinesis, necrosis and angiogenesis in tumors. In result, BLM assay, highly consisted with MTT assay, showed that 1,2,4,8 and 16 μmol/L As2O3 significantly inhibited the proliferation of 4T1-Luc cells, and the morphological observation and Annexin V/PI double-staining displayed the typical apoptotic characteristics in As2 O3-treated cells. As2O3 significantly inhibited the growth of murine 4T1 orthotopic breast cancer in vivo at a time- and dose-dependent manner,and the tumor-growth measurement by optical in vivo imaging was better than by tumor weighing. After AS2O3 administration,the pathological and immunocytochemical measurement showed that the numbers of mitotic cells and microvessels in tumor tissue markedly decreased, and

  1. Poisoning of bees by industrial arsenic emissions

    Energy Technology Data Exchange (ETDEWEB)

    Jaroslav, S.

    1962-01-01

    Massive poisoning of bees by industrial arsenic emissions in Czechoslovakia are reviewed. Arsenic emissions from an ore processing plant in Tesin were responsible for massive bee deaths after World War I. Massive death of bees was observed in 1938 in the Krompach region around a copper ore smelting plant which emitted arsenic. Other accidents were reported in 1954 and 1957 in areas around industrial plants and power plants using arsenopyrite-containing low-grade coal or lignite. Arsenic was emitted bound in fly-ash in the form of arsenic trioxide or, in the case of coals containing alkaline chlorides, in the form of arsenic trichloride. The arsenic contamination extended to areas within a radius of 3 to 7 km. Settled fly-ash contained 0.0004 to 0.75 percent arsenic, which was soluble in a citrate-hydrochloric acid solution of pH 3.9, which corresponds to the gastric acid of bees. The arsenic uptake by the bees from pollen was calculated to amount to 1 microgram daily, against a toxic dose of 0.37 microgram. The toxic effect of arsenic on bees can be abated by adding colloidal iron hydroxide to the sugar solution which they are fed.

  2. Poisoning of bees by industrial arsenic emissions

    Energy Technology Data Exchange (ETDEWEB)

    Svoboda, J.

    1962-01-01

    Massive poisoning of bees by industrial arsenic emissions in Czechoslovakia are reviewed. Arsenic emissions from an ore processing plant in Tesin were responsible for massive bee deaths after World War I. Massive death of bees was observed in 1938 in the Krompach region around a copper ore smelting plant which emitted arsenic. Other accidents were reported in 1954 and 1957 in areas around industrial plants and power plants using arsenopyrite-containing low-grade coal or lignite. Arsenic was emitted bound in fly-ash in the form of arsenic trioxide or, in the case of coals containing alkaline chlorides, in the form of arsenic trichloride. The arsenic contamination extended to areas within a radius of 3-7 km. Settled fly-ash contained 0.0004-0.75% arsenic, which was soluble in a citrate-hydrochloric acid solution of pH 3.9, which corresponds to the gastric acid of bees. The arsenic uptake by the bees from pollen was calculated to amount to 1 microgram daily, against a toxic dose of 0.37 microgram. The toxic effect of arsenic on bees can be abated by adding colloidal iron hydroxide to the sugar solution which they are fed. 5 references.

  3. Effects of co-treatment with puerariae radix flavones and arsenic trioxide on proliferation and apoptosis of Kasumi-1 cells and HL-60 cells%葛根总黄酮联合三氧化二砷对Kasumi-1和HL-60细胞增殖和凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    唐宇宏; 邵化敏; 朱红青; 姜鹏君; 季建敏; 沈群

    2011-01-01

    目的 探讨葛根总黄酮(PRF)联合三氧化二砷(ATO)对M2型急性髓系白血病细胞株Kasumi-1和HL-60细胞增殖和凋亡的影响.方法 以100 μg/mL PRF和1μmoL/L ATO联合处理Kasumi-1和HL-60细胞48 h(RRF+ ATO组),MTT法检测细胞增殖抑制率,Annexin V-FITC/PI双染法流式细胞术检测细胞早期凋亡率,Real-Time PCR检测凋亡抑制基因Bcl-2、Survivin mRNA表达,Western blotting检测细胞凋亡相关蛋白酶Caspase-3、-8、-9的表达.设立单用100μg/mL PRF的PRF处理组和空白对照组.结果 RRF+ ATO组Kasum-1细胞增殖抑制率、早期凋亡率以及Caspase-3、-9表达均显著高于PRF处理组(P<0.05),细胞中Bcl-2 mRNA表达的下调趋势明显.RRF+ ATO组HL-60细胞各项指标检测结果 与PRF处理组比较差异均无统计学意义(P>0.05).结论 PRF联合ATO能有效抑制Kasumi-1细胞增殖并诱导早期凋亡,而对HL-60细胞则无明显影响.%Objective To investigate the effects of co-treatment with puerariae radix flavones (PRF) and arsenic trioxide ( ATO) on proliferation and apoptosis of Kasumi-1 cells and HL-60 cells of acute myeloid leukemia Ml. Methods Kasumi-1 cells and HL-60 cells were treated with 100 jig/mL PRF and 1 funol/L ATO for 48 h (RRF + ATO group). MTT assay was employed to measure the inhibition rate of cell proliferation, Annexin V-FITC/PI double staining was used to determine the early apoptosis rate by flow cytometry, the expression of Bcl-2 and Survivin mRNA was detected by Real-Time PCR, and the expression of Caspase-3, Caspase-8 and Caspase-9 protein was detected by Western blotting. Cells only treated with 100 (ig/mL PRF were served as PRF group, and blank control group was also established. Results The inhibition rate of cell proliferation, early apoptosis rate and expression of Caspase-3 and Caspase-9 protein of Kasumi-1 cells in RRF + ATO group were significantly higher than those in PRF group (P 0.05). Conclusion Co-treatment with PRF and ATO can effectively

  4. 三氧化二砷通过抑制IKK/NF-κB信号通路活化发挥促乳腺癌细胞凋亡效应%Arsenic trioxide induces apoptosis in MCF7 human breast cancer cells by inhibiting IKK/NF-κB pathway activation

    Institute of Scientific and Technical Information of China (English)

    郝一; 李译; 高明; 董雯; 胡美茹; 宋伦

    2012-01-01

    目的 探讨IKK/NF-κB信号通路在三氧化二砷(As2O3)诱导乳腺癌细胞凋亡反应中的作用.方法 以乳腺癌细胞MCF7为靶细胞,以As2O3为刺激源,锥虫蓝(台盼蓝)拒染方法检测死亡细胞比率;双荧光素酶报告基因法检测MCF7细胞中NF-κB的活化状态;Western印迹方法检测IKK/NF-κB途径各信号分子的表达水平和活化状态;RT-PCR方法检测IKK/NF-κB途径下游靶基因的表达水平.结果 As2O3可显著诱导MCF7细胞凋亡;同时NF-κB的转录活化水平及其下游凋亡反应相关靶基因的表达水平也明显下降.在此过程中,I-κB的表达水平和NF-κB关键组成亚基(p65、p50)的核浆分布状态没有改变,但IKK激酶的两个催化亚基IKKα和IKKβ的表达水平明显下调.一过性高表达IKKα和IKKβ不仅能够恢复NF-κB的活化状态,而且能够拮抗As2O3诱导的乳腺癌细胞凋亡反应.结论 As2O3可通过在蛋白激酶水平抑制IKK/NF-κB信号通路活化从而发挥促乳腺癌细胞凋亡效应.%Objective To explore the role of IKK/NF-kB signaling pathway in mediating the apoptotic effect in human breast cancer cells exposed to arsenic trioxide (arsenite, As2O3). Methods MCF7 cells were treated with arsenite. Cell death was detected by phenol blue staining. Luciferase assay was used to detect the transactivation status of NF -kB in the MCF7 cells. The expression levels of IKKa, IKKP,I-kB and the cytoplasmic/nuclear distribution of p65 and p50 were detected by Western blotting. The expression levels of NF-kB downstream target genes were determined by RT-PCR. Results Arsenite induced apoptosis in MCF7 cells, along with significant inhibition of NF -kB transactivation and NF-kB target genes expression. Interestingly, the expression level of I-kB and cytoplasmic/nuclear distribution of p65 and p50 were not altered, but both IKKa and IKKp levels were dramatically down-regulated under the same conditions. Moreover, overexpressed IKKa or IKKp recovered

  5. 8-chloroadenosine 3 ', 5 '-monophosphate induces apoptosis of multiple myeloma cells catalyzed by arsenic trioxide%8-氯腺苷酸诱导多发性骨髓瘤细胞凋亡及三氧化二砷的催化作用

    Institute of Scientific and Technical Information of China (English)

    程毅敏; 唐勇; 姚一芸; 邹丽芳; 朱琦

    2013-01-01

    Objective To investigate the response of multiple myeloma (MM) cells to 8-chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) and the impact of arsenic trioxide (As2O3) on the above reaction.Methods MM-derived cell lines RPMI8226 and U266 were used as in vitro models.Cell apoptosis was evaluated according to cellular morphology and DNA content measured by flow cytometry.Meanwhile,rhodamine 123 (Rh123) staining and flow cytometry assay were used to detect the changes of mitochondrial transmembrane potentials (△ψm) in MM cells before and after the treatment.The synergic effects of 8-Cl-cAMP and As2O3 were evaluated by King' s formula.Results The 8-Cl-cAMP could induce growth inhibition of RPMI8226 and U266 cells in dose and time-related manners.The 8-Cl-cAMP could trigger apoptosis and △ψm collapse in MM cells through cellular morphology and flow cytometry analysis.As2O3 accelerated 8-Cl-cAMP-mediated apoptosis of RPMI8226 cells,but there were few synergic effects observed.Conclusion 8-Cl-cAMP could induce cell proliferation inhibition and apoptosis in MM cells.Mitochondria may be one of targets in 8-Cl-cAMP-mediated apoptosis.Furthermore,As2O3 catalyzes 8-Cl-cAMP-induced apoptosis.%目的 探究8-氯腺苷酸(8-Cl-cAMP)对多发性骨髓瘤(MM)细胞的作用和三氧化二砷(As2O3)对其影响.方法 以MM细胞株RPMI 8226和U266细胞为体外模型,应用形态学和流式细胞术检测细胞DNA含量分布和细胞凋亡.以罗丹明染色检测线粒体跨膜电位,并以金氏公式评价8-Cl-cAMP和As2O3之间的协同效应.结果 1~30 mol/L 8-Cl-cAMP能够明显抑制RPMI 8226和U266细胞的生长,并显著降低其细胞活力,呈时间和浓度依赖性.细胞形态学和流式细胞术分析显示,8-Cl-cAMP诱导骨髓瘤细胞凋亡并伴有线粒体跨膜电位的崩塌.As2O3能促进RPMI 8226细胞凋亡,但与8-Cl-cAMP无协同作用.结论8-Cl-cAMP能够在体外有效地抑制MM细胞生长并诱导其凋亡,线粒体可能是8-Cl-cAMP

  6. Arsenic in the aetiology of cancer.

    Science.gov (United States)

    Tapio, Soile; Grosche, Bernd

    2006-06-01

    Arsenic, one of the most significant hazards in the environment affecting millions of people around the world, is associated with several diseases including cancers of skin, lung, urinary bladder, kidney and liver. Groundwater contamination by arsenic is the main route of exposure. Inhalation of airborne arsenic or arsenic-contaminated dust is a common health problem in many ore mines. This review deals with the questions raised in the epidemiological studies such as the dose-response relationship, putative confounders and synergistic effects, and methods evaluating arsenic exposure. Furthermore, it describes the metabolic pathways of arsenic, and its biological modes of action. The role of arsenic in the development of cancer is elucidated in the context of combined epidemiological and biological studies. However, further analyses by means of molecular epidemiology are needed to improve the understanding of cancer aetiology induced by arsenic.

  7. 三氧化二砷维持治疗急性早幼粒细胞白血病对患者血脂代谢及远期生存率的影响%Effect of arsenic trioxide on blood lipid metabolism and long-term survival rate in patients with APL

    Institute of Scientific and Technical Information of China (English)

    廖永梅; 王淋; 王秀梅; 何雪花; 梁元碧

    2016-01-01

    Objective To investigate the effect of arsenic trioxide on blood lipid metabolism and long-term survival rate in patients with acute early immature granulocyte (APL),in order to provide a basis for finding an ideal maintenance therapy.Methods Ninety APL patients with complete remission were enrolled in the study,who were assigned into group A,B and C using random single blind meth-od.All three groups were treated with arsenic trioxide (ATO)combined with all trans retinoic acid (ATRA)in the treatment.After complete remission group A was treated with ATO therapy,group B ATRA therapy,and group C ATRA and ATO alternately for mainte-nance therapy.Observe the three groups before of Serum total cholesterol (TC),triglyceride(TG)changes and adverse drug reactions in all three groups were observed before treatment,after complete remission,one cycle of maintenance treatment,and 2 cycles of mainte-nance treatment.After 2 courses of maintenance treatment,all patients were followed up for a period of 2 years and the survival and re-currence rate in the three groups were observed.Results There were no significant differences in blood lipids among all three groups before and after treatment respectively.In all three groups,the indexes of blood lipids after 2 cycles of maintenance treatment were all lower than those before treatment,after complete remission,and after 1 cycle of maintenance treatment (P <0.05).There were adverse reactions in all three groups,with no significant difference in incidence of adverse reaction between group A and group C and a higher incidence of intracranial hypertension in group B than in group C (P <0.05),and group A respectively (P <0.05).One year after maintenance treatment,there were no significant differences in survival and recurrence rate among the three groups.Two years after ma-intenance treatment,a lower survival rate was found in group B than in group C (P <0.05).There were no significant difference in re-currence rate among the three groups

  8. Clinical study of children with acute promyelocytic leukemia treated with arsenic trioxide with positive PML -RARa fusion gene%以亚砷酸为主的方案治疗 PML-RARa 阳性急性早幼粒细胞白血病

    Institute of Scientific and Technical Information of China (English)

    朱嘉莳; 蒋慧; 陆正华; 杨静薇; 邵静波; 李红; 廖雪莲; 张娜

    2016-01-01

    未来的发展趋势。%Objective To evaluate the efficacy of different treatment regimens for children with acute promye-locytic leukemia (APL)with positive PML -RARa fusion gene.Methods Thirty -two newly diagnosed APL patients were included in this study,treated either with all -trans -retinoic acid (ATRA)and chemotherapy (CT)(group A) or with ATRA and arsenic trioxide (ATO)(group B).Clinical situation and clinical efficacy were analyzed in patients in different groups.They were also separated into low risk group,intermediate risk group and high risk group according to different risk criteria.Clinical characteristics,complete remission,long -time survival and urine arsenic concentra-tion were analyzed and compared.Results (1 )Fourteen of 1 5 patients (93.3%)in group A achieved hematological complete remission (HCR)with a median time of 38 days (28 -63 days).Sixteen of 1 7 patients (94.1 %)in group B achieved HCR with a median time of 29 days (1 0 -42 days),which was significantly shorter than group A,and there was a significant difference between 2 groups(t =3.53,P =0.002).(2)The 5 -year event -free survival (EFS)of group A and group B was (60.0 ±1 2.6)% and (81 .9 ±9.5)%,respectively;the 5 -year EFS of group B was almost 20% higher than group A;while there was no significant difference between the 2 groups(χ2 =1 .1 5,P =0.28).The 5 -year overall survival (OS)of group A and group B was (72.2 ±1 1 .9)% and (94.1 ±5.7)%,respectively,the 5 -year OS of group B was almost 20% higher than group A;while there was no significant difference between the 2 groups(χ2 =2.88,P =0.1 6).(3)The 5 -year EFS of low plus intermediate group and high risk group patients was (74.0 ±1 0.1 )% and (64.8 ±1 4.3)%,the 5 -year EFS of low plus intermediate group was almost 1 0% higher than high risk group,but there was no significant difference between the 2 groups(χ2 =0.1 4,P =0.71 ).The 5 -year OS of low plus intermediate group and high risk group patients was (84.7 ±8.1 )% and (71 .3 ±1 4.1 )%,the 5 -year OS of

  9. Advances in Management of Acute Promyelocytic Leukemia with Arsenic Trioxide

    Institute of Scientific and Technical Information of China (English)

    MA Jun

    2007-01-01

    @@ Acute promyelocytic leukemia (APL), with specific features in cell morphology, is classified as M3 by French-American-British (FAB).Among M3, 95% of patients show specific chromosome translocation t(15;17)q(22;21) with PML-RAR α fusion gene, and 5% of patients show other subtypes. According to the statistical analysis of 2 540 adult acute myeloid leukemia (AML)cases in Harbin Institute of Hematology & Oncology, APL accounted for 23%.

  10. Study on the inhibitory effects of arsenic trioxide on the growth of endometrial cancer cells in vitro and in vivo%三氧化二砷抑制子宫内膜癌生长的体内外实验研究

    Institute of Scientific and Technical Information of China (English)

    胡美丽; 李利; 王晓玲; 顾国琴; 齐润辉; 康山

    2009-01-01

    Objective:To explore the inhibitory effect of arsenic troixide (ATO) on the growth of human endometrial cancer HEC-1-A cells in vitro and in vivo. Methods:Tetrazolium salt assay (MTT) was used to compare the inhibitory effect of ATO on HEC-1-A cells with that of progesterone, medroxyprogesterone acetate (MPA) and cisplatin (CDDP). Flow cytometry and DNA electrophoresis were used to determine the effects of ATO on cell cycle and apoptosis. Human endometrial cancer xenografted model was established in nude mice. The tumor-bearing nude mice were randomly divided into the experimental groups: ATO low dose group (4 mg·kg-1·d-1), medium dose group (6 mg·kg-1·d-1), high dose group (8 mg·kg-1·d-1), CDDP positive control group (3 mg·kg-1·d-1) and saline negative control group. The drugs were administered intraperitoneally for 14 consecutive days, and then the tumor volume and tumor inhibition rate were calculated. Results: ATO 1-20 μmol/L and CDDP markedly inhibited the cell growth. The inhibitory effect of ATO was higher than that of CDDP. ATO 5 μmol/L treatment induced apoptosis and arrested cells at S and G2/M phase. ATO 4, 6, and 8 mg·kg-1·d-1 and CDDP 3 mg·kg-1·d-1 inhibited tumor volume by 50.97%, 75.58%, 56.92%, and 52.23%, respectively; and inhibited the tumor weight by 10.15%, 29.33%, 16.67%, and 14.69%, respectively. The difference was significant compared with negative control group (P<0.05). Conclusion:ATO inhibited the growth of endometrial cancer cells HEC-1-A in vitro and in vivo. It may become a novel therapeutic reagent for the treatment of endometrial cancer.%目的:探讨三氧化二砷(arsenic trioxide, ATO)对人子宫内膜癌HEC-1-A细胞生长的抑制作用.方法:采用MTT法比较ATO、孕酮、安宫黄体酮(medroxyprogesterone acetate,MPA)和顺铂(cisplatin, CDDP)对HEC-1-A细胞的抑制作用,应用FCM和DNA电泳检测ATO对细胞周期和细胞凋亡的影响.建立裸鼠人子宫内膜癌移植瘤

  11. Topical photodynamic therapy with 5-ALA in the treatment of arsenic-induced skin tumors

    Science.gov (United States)

    Karrer, Sigrid; Szeimies, Rolf-Markus; Landthaler, Michael

    1995-03-01

    A case of a 62-year-old woman suffering from psoriasis who was treated orally with arsenic 25 years ago is reported. The cumulative dose of arsenic trioxide was 800 mg. Since 10 years ago arsenic keratoses, basal cell carcinomas, Bowen's disease and invasive squamous cell carcinomas mainly on her hands and feet have developed, skin changes were clearly a sequence of arsenic therapy. Control of disease was poor, her right little finger had to be amputated. Topical photodynamic therapy with 5-aminolevulinic acid was performed on her right hand. Clinical and histological examinations 6 months after treatment showed an excellent cosmetic result with no signs of tumor residue.

  12. 尿中碘的过硫酸铵消化-低砷量砷铈催化分光光度测定方法%Revised method with low usage amount of arsenic trioxide for testing urinary iodine by As(Ⅲ)-Ce4+ catalytic spectrophotometry using ammonium persulfate digestion

    Institute of Scientific and Technical Information of China (English)

    张亚平; 阎玉芹; 刘列钧; 孙毅娜; 李卫东; 华基礼; 黄嫣红; 李秀维; 赵立胜

    2013-01-01

    determination of urinary iodine with low usage amount of arsenic trioxide and by As(Ⅲ)-Ce4+ spectrophotometry using ammonium persulfate digestion.Methods The newly revised method include:improved detection steps of 0.0-300.0 μ4g/L range urinary iodine,and increased detection steps of 300.0-1200.0 μg/L range urinary iodine,usage amount of arsenious acid solution was only a quarter of usage amount of the current standard method.The new modification for the national standard method was introduced and the method was evaluated on standard curve linearity and linear range,sample detection limit,precision and accuracy.Results The linear correlation coefficients d the 0.0-300 μg/L range and 300.0-1200.0 μg/L range calibration curve[C =a + b × lgA,C:iodine concentration,A:measuring absorbance] were -0.9995--1.0000,-0.9994--1.0000,respectively.The detection limit for iodine was 2.0 μg/L(0.25 ml of urine was tested).The relative standard deviations were 0.9% (0.6/70.3)-3.3%(1.2/35.6) when measuring 12 urine samples with iodine conc entration of 35.6-265.5 μg/L,and 0.4% (2.0/517.3)-2.2% (7.2/330.1) when measuring 12 urine samples with iodine concentration of 330.0-1112.0 μg/L.The average recovery was 99.4% with a range of 93.8% (93.8/100)-103.9%(103.9/100) when measuring 15 urine samples with iodine concentration of 33.7-203.0 μg/L,and was 98.2% with a range of 91.2%(501.8/550)-102.9%(411.7/400) when measuring 15 urine samples with iodine concentration of 330.0-783.0 μg/L.At different test temperature,the test results of five urinary iodine national standard materials with iodine concentration of 73.0,88.0,175.0,206.0,212.0 μg/L were all within the given value range and the relative deviation range was-2.8%(-5.9/212)-3.9%(6.9/175),and the test results of two urinary iodine national standard materials with iodine concentration of 556.0 and 883.0 μg/L were all within the given value range and the relative deviation range was-0.7% (-7.0/883)-1.5%(8

  13. The impact of gene NDRG1 silence on the inhibitory effect of arsenic trioxide to cervical cancer%沉默NDRG1基因与三氧化二砷对宫颈癌抑制作用的研究

    Institute of Scientific and Technical Information of China (English)

    张海艳; 耿晓星; 马荣; 唐丽萍

    2012-01-01

    Objective To observe the impact of gene NDRG1 silence on the inhibitory effect of arsenic trioxide ( As2Oj) to the growth of cervical cancer HeLa cell, and discuss the mechanism of inhibitory effect of As2O3 on cervical cancer and their correlation with NDRG1 gene. Methods miRNA interference vector of gene NDRGlwas construced and stably transfected into human cervical cancer HeLa cells. The expression of NDRG1 mRNA in cervical cancer HeLa cells was investigated by RT-PCR technique. As203of different concentrations was used to act on HeLa cells before and after transfection. MTT colorimetry method was used to test the growth and apoptosis of these cells. Results Semi-quantitative RT-PCR technique showed that miRNA interference vector of gene NDRG1 was successfully transfected into cervical cancer HeLa cells, and could effectively inhibit the expression of NDRG1 mRNA. As2O3 could inhibit the growth of HeLa cells before and after transfection and the difference was statistically significant in a concentration dependent manner(P<0. 05) ,and the inhibition enhanced with the extension of time. The highest inhibiting rate was (49. 9 ±0. 6)% in HeLa cells and (43. 1 ±0.8)% in transtecled HeLa cells of 12. 0u,mol/L As2O3at 72h. The inhibiting effect of the same concentration As2 0, to HeLa cells after transfection was weaker than HeLa cells before transfection (P < 0.05). Conclusion The silence of gene NDRG1 can decrease the inhibiting effect of As2O3 to the growth of HeLa cells, indicating that the inhibiting effect of As2O3 to the growth of Hela cells is correlated to gene NDRG1.%目的 观察沉默细胞分化相关基因NDRG1在三氧化二砷(As2O3)抑制宫颈癌HeLa细胞生长过程中的作用,探讨As2O3对宫颈癌的抑制作用与NDRG1基因的相关性.方法 构建NDRG1基因的miRNA干扰载体,稳定转染人宫颈癌HeLa细胞,半定量RT-PCR检测转染后HeLa细胞中NDRG1 mRNA的表达;不同浓度As2O3分别作用于转染及未转染HeLa细

  14. [Noncirrhotic liver fibrosis after chronic arsenic poisoning].

    Science.gov (United States)

    Piontek, M; Hengels, K J; Borchard, F; Strohmeyer, G

    1989-10-27

    A 67-year-old woman with portal hypertension, splenomegaly without portal vein thrombosis, leucopenia and thrombocytopenia of splenic origin had repeated episodes of life-threatening haemorrhage from esophageal varices. Since childhood she had suffered from psoriasis and had been treated over a period of 15 years with Fowler's solution (in all about 25 g of arsenic trioxide). She had the characteristic skin lesions of arsenical poisoning-palmar hyperkeratoses and two basal cell carcinomas on the trunk. Histological examination of a wedge biopsy from the liver showed definite structural changes with fibrosis around the central veins and in the portal tracts. There was no evidence of cirrhotic alteration. The hepatocytes were normal by light microscopy and electron microscopy. This case of noncirrhotic hepatic fibrosis is considered to have been caused by chronic arsenical poisoning.

  15. Arsenic toxicity in mice and its possible amelioration

    Institute of Scientific and Technical Information of China (English)

    R. J. Verma; Archana Vasu, Abdu; Alim Saiyed

    2004-01-01

    Oral administration of arsenic trioxide(3 and 6 mg/kg body weight/d) for 30 d caused, as compared with vehicle control, dose- dependent significant reductions in body weight, absolute weight, protein, glycogen, as well as, total, dehydro and reduced ascorbic acid contents both in the liver) and kidney of arsenic- treated mice. Succinic dehydrogenase(SDH) and phosphorylase(only in the liver activities were significantly reduced in a dose-dependent manner. Acid phosphatase activity was significantly decreased in the liver of low dose arsenic-treated animals; however, significant rise in its activity was observed in high dose group. As compared with vehicle control, treatment also caused significant dose-dependent reductions in SDH, alkaline phosphatase and acid phosphatase activities in the kidney of mice. Vitamin E cotreatment as well as, 30 d withdrawal of arsenic trioxide treatment with or without vitamin E caused significant amelioration in arsenic-induced toxicity in mice. Administration of vitamin E during withdrawal of treatment also caused significant amelioration as compared from only withdrawal of the treatment. It is concluded that vitamin E ameliorates arsenic-induced toxicities in the liver and kidney of mice.

  16. Gene Analysis of Arsenic Trioxide—induced Apoptosis of Lymphoma Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANGZidong; LIWeiyu; 等

    2002-01-01

    Objective The effect of arsenic trioxide on apoptosis gene expression of Raji cell was explored when Raji cells were incubated with 0.5μmol/L of arsenic trioxide for 6h。Methods Cell culture,extraction and isolation of mRNA,preparation of probes labeled with fluorescence,hybridization technique of DNA chip(each chip containing 200 apoptosis genes,Chinese Shanghai Biostar,In.)were used.Results Arsenic trioxide induced significant changes in 10%(20/200 genes)of the apoptosis genes:18 genes were downregulated,only two upregulated.In particular,inhibitors of apoptosis protein,such as X-linked inhibitor of apoptosis protein,were significantly downregulated.P53 and the other apoptosis genes were also downregulatec.Of the upregulated genes,high expression of heat-shock protein could promote apoptosis of Raji cells.Conclusion The inhibitors of apoptosis protein play an important role in the process of arsenic trioxide-induced apoptosis of Raji cells.

  17. Adverse effect of arsenic trioxide treatment on vital organs in the process of treating childhood acute promyelocytic leukemia%三氧化二砷致小儿急性早幼粒细胞白血病器官功能损害的临床研究

    Institute of Scientific and Technical Information of China (English)

    王弘; 王晔; 李爽; 迟昨非; 郝良纯

    2014-01-01

    Objective To explore the adverse effect of arsenic trioxide (As2O3) on liver,kidney and heart function during treating children patients with acute promyelocytic leukemia (APL) at therapeutic dose.Methods Sixty-five APL cases received As2O3 by intravenous drip and organic toxicity were selected as our subjects.The indices of liver,heart and kidney were measured.Results Of all subjects,19 cases(29.2%) occurred liver damage,including 15 cases(23.1%) mild and 4 cases(6.2%) moderate toxicity.The levels of alanine aminotransferase of patients before treatment was (19.9 ±9.5) U/L,and (24.3 ± 11.8) U/L,(25.0 ± 14.4) U/L at 1 st and 2nd weeks after treatment,higher than those before the treatment (P < 0.05).However,level of alanine aminotransferase was back to normal at 3th weeks after treatment.Meanwhile the levels of aspartate aminotransferase at 1st,2nd and 3th weeks after treatment were (38.3 ± 16.5),(39.1 ± 15.5),(35.3 ± 20.6) U/L respectively,higher than that before treatment((28.5 ± 8.8) U/L,P < 0.05 or 0.01),and it was back to normal at 4th weeks.(2) The levels of urinary cystatin C were (2.51 ± 1.45) mg/L,(3.05 ± 1.13) mg/L,(2.46 ± 1.21) mg/L at 2nd,3th,4th weeks after treatment,significantly higher than that before treatment ((1.98 ±0.68) mg/L,P <0.05 or 0.01).And the levels of urinary β2 microglobulin at 2nd,3th,4th weeks after treatment were significantly higher than that before treatment (P <0.05 or 0.01) and back to normal at 5 weeks after treatment.(3) Nine cases at remission stage showed the symptoms of palpitation,precordial discomfort and increased heart rate,and all those symptoms were mild.And the symptoms disappear at the 3th week after the treatment.Creatine kinase at the 2nd weeks after treatment was (90.2 ± 32.5) U/L,higher than that before treatment ((78.5 ± 22.3) U/L).The levels of creatine kinase isoenzyme at 2nd,3th weeks after treatment were (8.3 ± 4.8) U/L,(8.5 ± 5.6) U/L,higher than that before treatment ((6.3

  18. microRNAs expression profile in acute promyelocytic leukemia cell differentiation induced by all-trans retinoic acid and arsenic trioxide%全反式维甲酸和三氧化二砷诱导急性早幼粒细胞白血病细胞分化前后微小RNA表达变化

    Institute of Scientific and Technical Information of China (English)

    吴勇; 李先芳; 杨景辉; 廖晓莹; 陈元仲

    2012-01-01

    目的 研究急性早幼粒细胞白血病(APL)细胞分化前后微小RNA(miRNA,miR)表达变化.方法 采用全反式维甲酸(ATRA)和三氧化二砷(As2O3)诱导APL细胞系NB4 细胞分化,瑞氏-姬姆萨染色观察细胞形态,流式细胞术检测细胞表面标志CD11b的表达,用实时定量RT-PCR检测miRNA表达谱miR-15b、miR-16、miR-34a、miR-107、miR-124a、miR-146、miR-155、miR-181a、miR-223、miR-342、let7c等miRNA的表达水平,用2-△△Ct法计算miRNA相对表达水平.收集15例APL初诊和15例APL缓解期患者骨髓单个核细胞(MNC),用RT-PCR检测MNC miRNA 的表达水平,用2-△Ct法计算miRNA表达水平.结果 ATRA作用NB4细胞96 h,miR-15b、miR-16、miR-107、miR-223、miR-342表达水平均显著上调,分别为对照组的3.40、4.22、5.41、20.03和5.29倍,As2O3作用NB4细胞96 h,miR-15b、miR-16、miR-107、miR-223、miR-342表达水平也显著上调,分别为对照组的3.62、2.49、2.58、4.27和1.94倍,除miR-15b外,ATRA处理组miR-16、miR-107、miR-223和miR-342表达水平上调程度均高于As2O3处理组,其中尤以miR-223为甚.ATRA和As2O3治疗后缓解期APL患者miR-15b、miR-16、miR-107、miR-181a、miR-223和miR-342表达水平(2-△Ct值)分别为0.4137、0.6367、0.1260、0.0522、0.6611和0.0280,而APL初诊患者miR-15b、miR-16、miR-107、miR-181a、miR-223、miR-342表达水平分别为0.0751、0.2022、0.0425、0.3064、0.1733和0.0090,APL缓解期miR-15b、miR-16、miR-107、miR-223和miR-342表达水平高于APL初诊者(P值均<0.05),而APL缓解期miR-181a表达水平低于APL初诊者(P<0.05).结论 特定miRNA参与APL细胞分化过程.%Objective To study the expression profile of microRNAs in acute promyelocytic leukemia (APL) cells during differentiation. Methods Differentiation of APL cell line NB4 cells was induced by all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3). Morphological and immunological assay was performed by Wright-Giemsa staining and flow

  19. Analytical artefacts in the speciation of arsenic in clinical samples

    Energy Technology Data Exchange (ETDEWEB)

    Slejkovec, Zdenka [Jozef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia)], E-mail: zdenka.slejkovec@ijs.si; Falnoga, Ingrid [Jozef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia); Goessler, Walter [Institute of Chemistry - Analytical Chemistry, Karl-Franzens University Graz, Universitaetsplatz 1, Graz (Austria); Elteren, Johannes T. van [National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana (Slovenia); Raml, Reingard [Institute of Chemistry - Analytical Chemistry, Karl-Franzens University Graz, Universitaetsplatz 1, Graz (Austria); Podgornik, Helena; Cernelc, Peter [University Medical Centre Ljubljana, Zaloska 7, 1000 Ljubljana (Slovenia)

    2008-01-21

    Urine and blood samples of cancer patients, treated with high doses of arsenic trioxide were analysed for arsenic species using HPLC-HGAFS and, in some cases, HPLC-ICPMS. Total arsenic was determined with either flow injection-HGAFS in urine or radiochemical neutron activation analysis in blood fractions (in serum/plasma, blood cells). The total arsenic concentrations (during prolonged, daily/weekly arsenic trioxide therapy) were in the {mu}g mL{sup -1} range for urine and in the ng g{sup -1} range for blood fractions. The main arsenic species found in urine were As(III), MA and DMA and in blood As(V), MA and DMA. With proper sample preparation and storage of urine (no preservation agents/storage in liquid nitrogen) no analytical artefacts were observed and absence of significant amounts of alleged trivalent metabolites was proven. On the contrary, in blood samples a certain amount of arsenic can get lost in the speciation procedure what was especially noticeable for the blood cells although also plasma/serum gave rise to some disappearance of arsenic. The latter losses may be attributed to precipitation of As(III)-containing proteins/peptides during the methanol/water extraction procedure whereas the former losses were due to loss of specific As(III)-complexing proteins/peptides (e.g. cysteine, metallothionein, reduced GSH, ferritin) on the column (Hamilton PRP-X100) during the separation procedure. Contemporary analytical protocols are not able to completely avoid artefacts due to losses from the sampling to the detection stage so that it is recommended to be careful with the explanation of results, particularly regarding metabolic and pharmacokinetic interpretations, and always aim to compare the sum of species with the total arsenic concentration determined independently.

  20. Interactions of arsenic and phenanthrene on their uptake and antioxidative response in Pteris vittata L

    Energy Technology Data Exchange (ETDEWEB)

    Sun Lu [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100049 (China); Yan Xiulan [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China); Liao Xiaoyong, E-mail: liaoxy@igsnrr.ac.cn [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China); Wen Yi; Chong Zhongyi; Liang Tao [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China)

    2011-12-15

    The interactions of arsenic and phenanthrene on plant uptake and antioxidative response of Pteris vitatta L. were studied hydroponically. The combination of arsenic and phenanthrene decreased arsenic contents in fronds by 30-51%, whereas increased arsenic concentrations 1.2-1.6 times in roots, demonstrating the suppression of arsenic translocation compared to the corresponding treatment without phenanthrene. Under the co-exposure, As(III) concentrations in fronds deceased by 12-73%, and at higher arsenic exposure level ({>=}10 mg/L), As(V) in fronds and As(III) in roots increased compared to the single arsenic treatment. Arsenic exposure elevated phenanthrene concentrations in root by 39-164%. The co-existence of arsenic and phenanthrene had little impact on plant arsenic accumulation, although synergistic effect on antioxidants was observed, suggesting the special physiological process of P. vitatta in the co-exposure and application potential of P. vitatta in phytoremediation of arsenic and PAHs co-contamination. - Highlights: > Pteris vitatta L. show tolerance to the arsenic and phenanthrene co-exposure. > P. vitatta efficiently accumulate arsenic and simultaneously enhance phenanthrene dissipation. > Phenanthrene suppresses arsenic translocation from roots to fronds. > Phenanthrene causes As(III) elevation in roots while reduction in fronds. > Synergistic effect potentiates the toxicity and antioxidants in plant. - Pteris vitatta L. not only efficiently accumulate arsenic but also enhance phenanthrene dissipation under the arsenic and phenanthrene co-exposure.

  1. Arsenic ototoxicity

    Institute of Scientific and Technical Information of China (English)

    Gulin Gokçen Kesici

    2016-01-01

    High levels of arsenic are found in many parts of the world and more than 100 million people may have been exposed to it. There is growing evidence to indicate that arsenic has a deleterious effect on the auditory system. This paper provides the general information of arsenic and its ototoxic effects.

  2. Airborne arsenic and urinary excretion of arsenic metabolites during boiler cleaning operations in a Slovak coal-fired power plant.

    Science.gov (United States)

    Yager, J W; Hicks, J B; Fabianova, E

    1997-08-01

    Little information is available on the relationship between occupational exposure to inorganic arsenic in coal fly ash and urinary excretion of arsenic metabolites. This study ws undertaken in a coal-fired power plant in Slovakia during a routine maintenance outage. Arsenic was measured in the breathing zone of workers during 5 consecutive workdays, and urine samples were obtained for analysis of arsenic metabolites--inorganic arsenic (Asi), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)--prior to the start of each shift. Results from a small number of cascade impactor air samples indicated that approximately 90% of total particle mass and arsenic was present in particle size fractions >/= 3.5 micron. The 8-hr time-weighted average (TWA) mean arsenic air concentration was 48.3 microg/m3 (range 0.17-375.2) and the mean sum of urinary arsenic (SigmaAs) metabolites was 16.9 microg As/g creatinine (range 2.6-50.8). For an 8-hr TWA of 10 microg/m3 arsenic from coal fly ash, the predicted mean concentration of the SigmaAs urinary metabolites was 13.2 microg As/G creatinine [95% confidence interval (CI), 10.1-16.3). Comparisons with previously published studies of exposure to arsenic trioxide vapors and dusts in copper smelters suggest that bioavailability of arsenic from airborne coal fly ash (as indicated by urinary excretion) is about one-third that seen in smelters and similar settings. Arsenic compound characteristics, matrix composition, and particle size distribution probably play major roles in determining actual uptake of airborne arsenic. PMID:9347899

  3. The chemical composition of mineral trioxide aggregate

    OpenAIRE

    Camilleri Josette

    2008-01-01

    Mineral trioxide aggregate (MTA) is composed of Portland cement, with 4:1 addition of bismuth oxide added so that the material can be detected on a radiograph. The cement is made up of calcium, silicon and aluminium. The main constituent phases are tricalcium and dicalcium silicate and tricalcium aluminate. There are two commercial forms of MTA, namely the grey and the white. The difference between the grey and the white materials is the presence of iron in the grey material, which makes up t...

  4. Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic.

    Science.gov (United States)

    Zhang, Hai-Nan; Yang, Lina; Ling, Jian-Ya; Czajkowsky, Daniel M; Wang, Jing-Fang; Zhang, Xiao-Wei; Zhou, Yi-Ming; Ge, Feng; Yang, Ming-Kun; Xiong, Qian; Guo, Shu-Juan; Le, Huang-Ying; Wu, Song-Fang; Yan, Wei; Liu, Bingya; Zhu, Heng; Chen, Zhu; Tao, Sheng-Ce

    2015-12-01

    Arsenic is highly effective for treating acute promyelocytic leukemia (APL) and has shown significant promise against many other tumors. However, although its mechanistic effects in APL are established, its broader anticancer mode of action is not understood. In this study, using a human proteome microarray, we identified 360 proteins that specifically bind arsenic. Among the most highly enriched proteins in this set are those in the glycolysis pathway, including the rate-limiting enzyme in glycolysis, hexokinase-1. Detailed biochemical and metabolomics analyses of the highly homologous hexokinase-2 (HK2), which is overexpressed in many cancers, revealed significant inhibition by arsenic. Furthermore, overexpression of HK2 rescued cells from arsenic-induced apoptosis. Our results thus strongly implicate glycolysis, and HK2 in particular, as a key target of arsenic. Moreover, the arsenic-binding proteins identified in this work are expected to serve as a valuable resource for the development of synergistic antitumor therapeutic strategies.

  5. Arsenic poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Schoolmeester, W.L.; White, D.R.

    1980-02-01

    Arsenic poisoning continues to require awareness of its diverse clinical manifestations. Industry is the major source of arsenic exposure. Although epidemiologic studies strongly contend that arsenic is carcinogenic, there are little supportive research data. Arsenic poisoning, both acute and chronic, is often overlooked initially in the evaluation of the patient with multisystem disease, but once it is suspected, many accurate methods are available to quantitate the amount and duration of exposure. Treatment with dimercaprol remains the mainstay of therapy, and early treatment is necessary to prevent irreversible complications.

  6. Mineral trioxide aggregate apexification: A novel approach

    Science.gov (United States)

    Purra, Aamir Rashid; Ahangar, Fayaz Ahmed; Chadgal, Sachin; Farooq, Riyaz

    2016-01-01

    The treatment of choice for necrotic teeth with immature root is apexification, which is induction of apical closure to produce more favorable conditions for conventional root canal filling. The most commonly advocated medicament is calcium hydroxide although recently considerable interest has been expressed in the use of mineral trioxide aggregate (MTA). MTA offers the option of a two-visit apexification procedure so that the fragile tooth can be restored immediately. However, difficulty in placing the material in the wide apical area requires the use of an apical matrix. Materials such as collagen, calcium sulfate, and hydroxyapatite have been used for this purpose. This article describes the use of resorbable suture material to form the apical matrix which offers many advantages over the contemporary materials. PMID:27563191

  7. Mineral trioxide aggregate apexification: A novel approach.

    Science.gov (United States)

    Purra, Aamir Rashid; Ahangar, Fayaz Ahmed; Chadgal, Sachin; Farooq, Riyaz

    2016-01-01

    The treatment of choice for necrotic teeth with immature root is apexification, which is induction of apical closure to produce more favorable conditions for conventional root canal filling. The most commonly advocated medicament is calcium hydroxide although recently considerable interest has been expressed in the use of mineral trioxide aggregate (MTA). MTA offers the option of a two-visit apexification procedure so that the fragile tooth can be restored immediately. However, difficulty in placing the material in the wide apical area requires the use of an apical matrix. Materials such as collagen, calcium sulfate, and hydroxyapatite have been used for this purpose. This article describes the use of resorbable suture material to form the apical matrix which offers many advantages over the contemporary materials. PMID:27563191

  8. THE SETTING MECHANISM OF MINERAL TRIOXIDE AGGREGATE

    Directory of Open Access Journals (Sweden)

    Halenur Altan

    2016-01-01

    Full Text Available Mineral trioxide aggregate (MTA is a powder containing calcium silicate composed of hydrophilic particles which harden at the presence of moisture. MTA was initially introduced as a root end filling material. Due its practical advantages that include superior biocompatility, effective sealing capability, and the ability to improve regeneration of the pulp and peripheral root tissues, it is used in different clinical applications such as pulp capping, apexification, pulpotomy and perforation. Despite being a promising material in endodontic treatment, MTA is not commonly used. Long setting time is the main clinical disadvantage of MTA. The aim of this review is to provide an overview of the current literature concerning the setting mechanism of MTA, accelerators and devices used to evaluate various steps of the hardening process.

  9. Effects of arsenic poisoning on neuronal cell apoptosis and mRNA and protein expression of calpain 1,calpain 2,and cdk5/p25

    Institute of Scientific and Technical Information of China (English)

    李新

    2014-01-01

    Objective To study the effect of arsenic on neuronal cell apoptosis and the mRNA and protein expression of calpain 1,calpain 2,and cyclin-dependent kinases 5(cdk5)/p25 and to provide a scientific basis for the research on neurotoxic mechanism of arsenic trioxide(As2O3).Methods Primary cultured rat neurons were divided into untreated control group,dimethyl sulfoxide

  10. Arsenic poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Low, D.G.

    1971-01-01

    The use of arsenic in ant poisons, herbicides, and insecticides affords the necessary contact with the poison by pets. Treatment was discussed in relation to two circumstances: very early poisoning in which the owner has observed ingestion of the arsenic, and when the signs of the poisoning are evident. Treatment for early ingestion involves emptying the stomach before the arsenic can pass in quantity into the intestine. This is followed with a 1% solution of sodium bicarbonate, with the administering of 3 to 6 mg of apomorphine. When signs of arsenic toxicity are already advanced, there is little advantage to be gained by either gastric lavage or administration of an emetic. The treatment then consists of the intramuscular administration of dimercaprol (BAL) at a dosage of 3 mg/lb of body weight three times a day until recovery. This is the specific antidote for arsenic. 1 reference.

  11. The MRP1-mediated effluxes of arsenic and antimony do not require arsenic-glutathione and antimony-glutathione complex formation.

    Science.gov (United States)

    Salerno, Milena; Petroutsa, Maria; Garnier-Suillerot, Arlette

    2002-04-01

    Arsenic trioxide is an effective treatment for acute promyelocytic leukemia, but resistance to metalloid salts is found in humans. Using atomic absorption spectroscopy, we have measured the rate of uptake of arsenic trioxide and of antimony tartrate in GLC4 and GLC4/ADR cells overexpressing MRP1 and the rate of their MRP1-mediated effluxes as a function of the intracellular GSH concentration. In sensitive cells, after 1 h, a pseudosteady state is reached where intra- and extracellular concentrations of metalloid are the same. This precludes the formation, at short term, of complexes between arsenic or antimony with GSH. In resistant cells reduced intracellular accumulation of arsenic (or antimony), reflecting an increased rate of arsenic (or antimony) efflux from the cells, is observed. No efflux of the metalloid is observed in GSH depleted cells. The two metalloids and GSH are pumped out by MRP1 with the same efficiency. Moreover for the three compounds 50% of the efflux is inhibited by 2 microM MK571. This led us to suggest that As- and Sb-containing species could be cotransported with GSH. PMID:12018890

  12. Pulp-Capping with Mineral Trioxide Aggregate

    Directory of Open Access Journals (Sweden)

    Peycheva Kalina

    2015-11-01

    Full Text Available There are two considerations for direct pulp capping - accidental mechanical pulp exposure and exposure caused by caries. Mineral trioxide aggregate (MTA was used as pulp-capping material to preserve the vitality of the pulpal tissues. Follow-up examinations revealed that treatment was successful in preserving pulpal vitality and continued development of the tooth. On the basis of available information, it appears that MTA is the material of choice for some clinical applications. Material and methods: Cases 18 - 8 teeth with grey MTA, 10 teeth with white MTA; diagnose: Pulpitis chronica ulcerosa, Electro pulpal test (EOD - 30-35 μA, pre-clinical X-ray - without changes in the structures, follow ups for 4 years. Successful treatments: without clinical symptoms and changes in the X-rays: 5 teeth with grey MTA, 8 teeth with white MTA for period of 4 years. Unsuccessful treatments: Clinical symptoms and sometimes changes in the X-ray: 3 with grey MTA, 2 with white MTA. MTA is an appropriate material for pulp-capping and follow-up examinations revealed that the treatment was successful in preserving pulpal vitality.

  13. Rapid Reduction in Breast Cancer Mortality With Inorganic Arsenic in Drinking Water

    Science.gov (United States)

    Smith, Allan H.; Marshall, Guillermo; Yuan, Yan; Steinmaus, Craig; Liaw, Jane; Smith, Martyn T.; Wood, Lily; Heirich, Marissa; Fritzemeier, Rebecca M.; Pegram, Mark D.; Ferreccio, Catterina

    2014-01-01

    Background Arsenic trioxide is effective in treating promyelocytic leukemia, and laboratory studies demonstrate that arsenic trioxide causes apoptosis of human breast cancer cells. Region II in northern Chile experienced very high concentrations of inorganic arsenic in drinking water, especially in the main city Antofagasta from 1958 until an arsenic removal plant was installed in 1970. Methods We investigated breast cancer mortality from 1950 to 2010 among women in Region II compared to Region V, which had low arsenic water concentrations. We conducted studies on human breast cancer cell lines and compared arsenic exposure in Antofagasta with concentrations inducing apoptosis in laboratory studies. Findings Before 1958, breast cancer mortality rates were similar, but in 1958–1970 the rates in Region II were half those in Region V (rate ratio RR = 0.51, 95% CI 0.40–0.66; p < 0.0001). Women under the age of 60 experienced a 70% reduction in breast cancer mortality during 1965–1970 (RR = 0.30, 0.17–0.54; p < 0.0001). Breast cancer cell culture studies showed apoptosis at arsenic concentrations close to those estimated to have occurred in people in Region II. Interpretation We found biologically plausible major reductions in breast cancer mortality during high exposure to inorganic arsenic in drinking water which could not be attributed to bias or confounding. We recommend clinical trial assessment of inorganic arsenic in the treatment of advanced breast cancer. PMID:25580451

  14. Determination of arsenic in antimony ingot and antimony trioxide by hydride generation-atomic fluorescence spectrometry%氢化物发生-原子荧光光谱法测定锑锭及三氧化二锑中的砷

    Institute of Scientific and Technical Information of China (English)

    钱光敏; 赵国杏

    2012-01-01

    The antimony slab and antimonous oxide samples were dissolved by sulfuric acid and hydrochloric acid, respectively. The Sb3+ in solution was precipitated with sodium hydroxide to separate trace arsenic from matrix antimony. The thiourea-ascorbic acid was added to reduce As5+ to As3+. Then, the arsenic in antimony slab and antimonous oxide was determined by atomic fluorescence spec-trometry. The hydride generation conditions were investigated: the concentration of reducing agent potassium borohydride was 25 g/L, the determination medium was 20% (V/V) hydrochloric acid, and the dosage of thiourea - ascorbic acid solution was 5 mL. The interference test of coexisting elements showed that, the interference of residual antimony in solution after precipitation could be fully eliminated by adding 1 mL of tartaric acid solution. Other impurity elements in sample did not interfere with the determination of arsenic after adding thiourea-ascorbic acid solution. The detection limit of method was 0. 156 ng/mL. The antimony slab and antimonous oxide samples were analyzed by the proposed method, and the relative standard deviation (RSD) was 0. 95%-1.2%. The determination results were consistent with those obtained by national standard methods.%采用硫酸溶解锑锭样品,盐酸溶解三氧化二锑样品,用氢氧化钠溶液使Sb3+沉淀从而使基体锑与微量砷分离,通过加入硫脲-抗坏血酸将As5+还原成As3+,然后在原子荧光仪上测定锑锭及三氧化二锑中的砷.对氢化物发生条件进行考察,确定还原剂硼氢化钾的浓度为25 g/L、测定介质为20%(V/V)盐酸、硫脲-抗坏血酸溶液用量为5 mL.共存元素干扰试验表明,沉淀后溶液中残留少量锑的干扰在加入1 mL酒石酸溶液后可以完全消除,而样品中其他杂质元素在加入硫脲-抗坏血酸溶液后不干扰砷的测定.方法的检出限为0.156 ng/mL.对锑锭及三氧化二锑样品进行分析,相对标准偏差为0.95%~1.2%,测定

  15. Bimetallic nanoparticles for arsenic detection.

    Science.gov (United States)

    Moghimi, Nafiseh; Mohapatra, Mamata; Leung, Kam Tong

    2015-06-01

    Effective and sensitive monitoring of heavy metal ions, particularly arsenic, in drinking water is very important to risk management of public health. Arsenic is one of the most serious natural pollutants in soil and water in more than 70 countries in the world. The need for very sensitive sensors to detect ultralow amounts of arsenic has attracted great research interest. Here, bimetallic FePt, FeAu, FePd, and AuPt nanoparticles (NPs) are electrochemically deposited on the Si(100) substrate, and their electrochemical properties are studied for As(III) detection. We show that trace amounts of As(III) in neutral pH could be determined by using anodic stripping voltammetry. The synergistic effect of alloying with Fe leads to better performance for Fe-noble metal NPs (Au, Pt, and Pd) than pristine noble metal NPs (without Fe alloying). Limit of detection and linear range are obtained for FePt, FeAu, and FePd NPs. The best performance is found for FePt NPs with a limit of detection of 0.8 ppb and a sensitivity of 0.42 μA ppb(-1). The selectivity of the sensor has also been tested in the presence of a large amount of Cu(II), as the most detrimental interferer ion for As detection. The bimetallic NPs therefore promise to be an effective, high-performance electrochemical sensor for the detection of ultratrace quantities of arsenic. PMID:25938763

  16. Arsenite as the probable active species in the human carcinogenicity of arsenic: mouse micronucleus assays on Na and K arsenite, orpiment, and Fowler's solution.

    OpenAIRE

    Tinwell, H; Stephens, S C; Ashby, J.

    1991-01-01

    Sodium arsenite, potassium arsenite, and Fowler's solution (arsenic trioxide dissolved in potassium bicarbonate) are equally active in the mouse bone marrow micronucleus assay (approximately 10 mg/kg by IP injection). The natural ore orpiment (principally As2S3) was inactive despite blood levels of arsenic of 300 to 900 ng/mL in treated mice at 24 hr. Sodium arsenite was active in three strains of mice. It is suggested that the human lung cancer observed among arsenic ore smelters and the ski...

  17. EMISSIONS OF SULFUR TRIOXIDE FROM COAL-FIRED POWER PLANTS

    Science.gov (United States)

    Emissions of sulfur trioxide (SO3) are a key component of plume opacity and acid deposition. Consequently, these emissions need to be low enough not to cause opacity violations and acid deposition. Generally, a small fraction of sulfur in coal is converted to SO3 in coal-fired co...

  18. Arsenic poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Furr, A.

    1977-01-01

    The route of arsenic exposure is usually by ingestion, thus the veterinarian is concerned with treating either an acute or a peracute condition. The arsenic compounds are considered to be highly toxic with a rapid onset of clinical signs. The toxicity and rapidity of onset are variable, depending upon the age and the species of animal. The chemical form and solubility of the toxicant also play a role in the course of the clinical syndrome. Inorganic arsenicals inhibit the sulfhydryl enzyme systems which are essential for normal cellular respiration and for metabolism of fats and carbohydrates. Therapeutic measures are intended to either remove or inactivate the unabsorbed material in the intestine, protect the alimentary tract, reverse the toxic syndrome and restore the homeostatic equilibrium of the animal. 5 references.

  19. Arsenic poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Low, D.G.

    1974-01-01

    The use of arsenic in ant poisons, herbicides, and insecticides affords the necessary contact with the poison by pets. The gastrointestinal tract appears to suffer the greatest though there may also be injury to the liver and kidneys. The treatments discussed were in relation to very early poisoning in which the owner had observed ingestion of the arsenic, and when the signs of the poisoning were evident. Early observation treatment included emptying the stomach before the arsenic passed in quantity into the intestine. If the signs of toxicity were already advanced, then the treatment consisted of the intramuscular administration of dimercaprol (BAL) at a dosage of 3 mg/lb of body weight three times a day until recovery. l reference.

  20. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    Science.gov (United States)

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

  1. Tungsten trioxide thin films prepared by electrostatic spray deposition technique

    International Nuclear Information System (INIS)

    Tungsten trioxide (WO3) thin films deposited on a Pt-coated alumina substrate using the electrostatic spray deposition (ESD) technique is reported in this paper. As precursor solution, tungsten (VI) ethoxide in ethanol was used. The morphology and the microstructure of the films were studied using scanning electron microscopy coupled with energy dispersive X-ray analysis, transmission electron microscopy, X-ray diffraction, and Raman spectroscopy. Dense to porous morphologies were obtained by tuning the deposition temperature. Impedance spectroscopy and current-voltage measurements were used to study the electrical behaviour of the films in air, in temperature range 300-500 deg. C. The activation energy was estimated from Arrhenius plots. Considering the obtained results, the ESD technique proved to be an effective technique for the fabrication of porous tungsten trioxide thin films

  2. Chemical characteristics of mineral trioxide aggregate and its hydration reaction

    OpenAIRE

    Chang, Seok-Woo

    2012-01-01

    Mineral trioxide aggregate (MTA) was developed in early 1990s and has been successfully used for root perforation repair, root end filling, and one-visit apexification. MTA is composed mainly of tricalcium silicate and dicalcium silicate. When MTA is hydrated, calcium silicate hydrate (CSH) and calcium hydroxide is formed. Formed calcium hydroxide interacts with the phosphate ion in body fluid and form amorphous calcium phosphate (ACP) which finally transforms into calcium deficient hydroxyap...

  3. Electric heating of a unit for uranium trioxide production

    International Nuclear Information System (INIS)

    Ammonium diuranate U2O7(NH4)2 containing about 50% of water is dried and transformed by calcination in uranium trioxide UO3. Drying and calcination was obtained by air heated by two burners using domestic fuel. In 1984 the plant was transformed for utilization of electric heating improving maintenance cost, decreasing heat losses and by energy saving the payback period on investment is of 2.6 years

  4. Lattice dynamics of rhenium trioxide from the quasiharmonic approximation

    OpenAIRE

    Wdowik, U.D.; Parlinski, K.; Chatterji, T.; Rols, S.; Schober, H.

    2010-01-01

    The quasiharmonic theory is applied to study the lattice dynamics and thermal properties of rhenium trioxide, a material exhibiting the negative thermal-expansion phenomenon. Phonons are calculated at several external pressures. The pressure dependence of the M, R, and zone-center phonon modes is analyzed. Relying on the Gruneisen formalism an influence of temperature on the M phonon mode is investigated. The calculated free energy of the system provides predictions for the temperature depend...

  5. Acute arsenic self-poisoning for suicidal purpose in a dentist: a case report.

    Science.gov (United States)

    Yilmaz, Y; Armagan, E; Olmez, Of; Esen, M; Alkis, N; Dolar, E

    2009-01-01

    Arsenic is a classical poison that has been historically used since ancient times for homicidal purposes. More recently, episodes of deliberate or unintentional arsenic self-poisoning have been increasingly reported. We describe here a case of a 77-year old male patient with a history of major depression, who attempted suicide by ingestion of 4 g of arsenic trioxide. The man, a dentist by profession, used arsenic preparations for pulp devitalization. The patient was admitted to our hospital 5 h after arsenic ingestion with nausea and vomiting. Plain radiograph of the abdomen showed radio-opaque material in the stomach and small intestine. Nasogastric lavage, activated charcoal, and chelators were used to remove arsenic. On day 3, endoscopy disclosed the presence of gastritis and superficial ulcers. The patient developed significant anemia (Hb: 8.7 g/dL on day 7) without significant signs of hemolysis. He gradually recovered from anemia within 5 months. The patient did not suffer any adverse outcome in spite of having ingesting 4 g of arsenic, approximately 20 times the lethal dose.

  6. Arsenic drinking water regulations in developing countries with extensive exposure.

    Science.gov (United States)

    Smith, Allan H; Smith, Meera M Hira

    2004-05-20

    The United States Public Health Service set an interim standard of 50 microg/l in 1942, but as early as 1962 the US Public Health Service had identified 10 microg/l as a goal which later became the World Health Organization Guideline for drinking water in 1992. Epidemiological studies have shown that about one in 10 people drinking water containing 500 microg/l of arsenic over many years may die from internal cancers attributable to arsenic, with lung cancer being the surprising main contributor. A prudent public health response is to reduce the permissible drinking water arsenic concentrations. However, the appropriate regulatory response in those developing countries with large populations with much higher concentrations of arsenic in drinking water, often exceeding 100 microg/l, is more complex. Malnutrition may increase risks from arsenic. There is mounting evidence that smoking and arsenic act synergistically in causing lung cancer, and smoking raises issues of public health priorities in developing countries that face massive mortality from this product. Also, setting stringent drinking water standards will impede short term solutions such as shallow dugwells. Developing countries with large populations exposed to arsenic in water might reasonably be advised to keep their arsenic drinking water standards at 50 microg/l.

  7. Arsenic and 17-β-estradiol bind to each other and neutralize each other's signaling effects.

    Science.gov (United States)

    Kumar, Sukhdeep; Mukherjee, Tapan K; Guptasarma, Purnananda

    2016-09-01

    We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other's independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spectroscopy, chromatography-coupled voltammometry and 1-D (1)H and (13)C NMR spectroscopy. Binding leads to attenuation of E2's hydroxyl (1)H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other's levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas. PMID:27346132

  8. Earth Abides Arsenic Biotransformations

    Science.gov (United States)

    Zhu, Yong-Guan; Yoshinaga, Masafumi; Zhao, Fang-Jie; Rosen, Barry P.

    2014-05-01

    Arsenic is the most prevalent environmental toxic element and causes health problems throughout the world. The toxicity, mobility, and fate of arsenic in the environment are largely determined by its speciation, and arsenic speciation changes are driven, at least to some extent, by biological processes. In this article, biotransformation of arsenic is reviewed from the perspective of the formation of Earth and the evolution of life, and the connection between arsenic geochemistry and biology is described. The article provides a comprehensive overview of molecular mechanisms of arsenic redox and methylation cycles as well as other arsenic biotransformations. It also discusses the implications of arsenic biotransformation in environmental remediation and food safety, with particular emphasis on groundwater arsenic contamination and arsenic accumulation in rice.

  9. Massive acute arsenic poisonings.

    Science.gov (United States)

    Lech, Teresa; Trela, Franciszek

    2005-07-16

    Arsenic poisonings are still important in the field of toxicology, though they are not as frequent as about 20-30 years ago. In this paper, the arsenic concentrations in ante- and post-mortem materials, and also forensic and anatomo-pathological aspects in three cases of massive acute poisoning with arsenic(III) oxide (two of them with unexplained criminalistic background, in which arsenic was taken for amphetamine and one suicide), are presented. Ante-mortem blood and urine arsenic concentrations ranged from 2.3 to 6.7 microg/ml, respectively. Post-mortem tissue total arsenic concentrations were also detected in large concentrations. In case 3, the contents of the duodenum contained as much as 30.1% arsenic(III) oxide. The high concentrations of arsenic detected in blood and tissues in all presented cases are particularly noteworthy in that they are very rarely detected at these concentrations in fatal arsenic poisonings. PMID:15939162

  10. The form, distribution and mobility of arsenic in soils contaminated by arsenic trioxide, at sites in southeast USA

    OpenAIRE

    Yang, Li; Donahoe, Rona J.

    2005-01-01

    Soils from many industrial sites in southeastern USA are contaminated with As because of the application of herbicide containing As2O3. Among those contaminated sites, two industrial sites, FW and BH, which are currently active and of most serious environmental concerns, were selected to characterize the occurrence of As in the contaminated soils and to evaluate its environmental leachability. The soils are both sandy loams with varying mineralogical and organic matter contents. Microwav...

  11. Arsenic-Based Drugs: From Fowler's Solution to Modern Anticancer Chemotherapy

    Science.gov (United States)

    Gibaud, Stéphane; Jaouen, Gérard

    Although arsenic is a poison and has a predominantly unfavorable reputation, it has been used as pharmaceutical agent since the first century BC. In 1786, Thomas Fowler reported the effects of arsenic in the cure of agues, remittent fevers, and periodic headaches. From this time on and despite abusive use, some interesting indications began to appear for trypanosomiasis, syphilis, and blood diseases. The first significant organoarsenical drug (atoxyl) was synthesized by Pierre Antoine Béchamp in 1859 by chemically reacting arsenic acid with aniline but additional experimentations on the properties of arsenic led Paul Ehrlich, the founder of chemotherapy, to the discovery of salvarsan in 1910. From the Second World War, Ernst A.H. Friedheim greatly improved the treatment of trypanosomiasis by melaminophenyl arsenicals. Until the 1990s some organoarsenicals were used for intestinal parasite infections but carcinogenic effects were displayed and all the drugs have been withdrawn in USA, in Europe, and elsewhere. In 2003, arsenic trioxide (Trisenox®) was re-introduced for the treatment of very specific hematological malignancies.

  12. Acute arsenic poisoning treated by intravenous dimercaptosuccinic acid (DMSA) and combined extrarenal epuration techniques.

    Science.gov (United States)

    Hantson, Philippe; Haufroid, Vincent; Buchet, Jean-Pierre; Mahieu, Paul

    2003-01-01

    Arsenic poisoning was diagnosed in a 26-year-old man who had been criminally intoxicated over the last two weeks preceding admission by the surreptitious oral administration of probably 10 g of arsenic trioxide (As2O3). The patient developed severe manifestations of toxic hepatitis and pancreatitis, and thereafter neurological disorders, respiratory distress, acute renal failure, and cardiovascular disturbances. In addition to supportive therapy, extrarenal elimination techniques and chelating agents were used. Dimercaprol (BAL) and dimercaptosuccinic acid (DMSA or succimer) were used simultaneously as arsenic chelating agents for two days, and thereafter DMSA was used alone. DMSA was administered by intravenous (20 mg/kg/d for five days, then 10 mg/kg/d for six days) and intraperitoneal route. Intravenous DMSA infusion was well tolerated and resulted in an increase in arsenic blood concentration immediately after the infusion. Continuous venovenous hemofiltration combined with hemodialysis, and peritoneal dialysis were proposed to enhance arsenic elimination. It was calculated that over an 11-day period 14.5 mg arsenic were eliminated by the urine, 26.7 mg by hemodialysis, 17.8 mg by peritoneal dialysis, and 7.8 mg by continuous venovenous hemofiltration. These amounts appeared negligible with regard to the probable ingested dose. The patient died on day 26 from the consequences of multiple organ failure, with subarachnoid hemorrhage and generalized infection caused by Aspergillus fumigatus.

  13. Apoptosis inducing effects of arsenic trioxide on human bladder cancer cell line BIU-87

    Institute of Scientific and Technical Information of China (English)

    童强松; 曾甫清; 赵军; 鲁功成; 郑丽端

    2001-01-01

    Objective To explore the apoptosis inducing effects of arsenictrioxide (As2O3) on human bladder cancer cells and elucidate possible mechanisms. Methods After treatment with As2O3, the growth inhibition rates of human bladder cancer cell line BIU-87 were studied by MTT and cell counts methods. DNA synthesis rates were detected by 3 H-TdR assay. The morphological changes of cancer cells were observed by light and electronic microscopy and cell apoptosis rates were detected by TdT-mediated dUTP nick end labeling (TUNEL). bcl-2 gene expression of BIU-87 cells was observed by strept avidin-biotin complex (SABC) immunohistochemical method. Results As2O3 could effectively inhibit the growth of BIU-87 (P<0.05), which were time and concentration dependent. The inhibition rate of 4.0?μmol/L As2O3 for DNA synthesis of cancer cells was 55.64% (P<0.01). Partial cancer cells presented the characteristic morphological changes of apoptosis which depended on the time of exposure to drug (P<0.05). bcl-2 expression of BIU-87 cells was decreased significantly (P<0.05). Conclusion As2O3 can significantly induce apoptosis in bladder cancer cells by down-regulating the expression of the bcl-2 gene and inhibiting DNA synthesis. This provides a potentially effective method for prevention and cure of human bladder cancer.%目的观察三氧化二砷(As2O3)对人膀胱癌细胞的诱导凋亡作用并探讨其机制。方法采用细胞计数和MTT法检测As2O3对人膀胱癌细胞株BIU-87的生长抑制作用;采用3H-TdR掺入法 检测癌细胞DNA合成速率;采用普通光镜、透射电镜观察癌细胞形态学变化;采用TUNEL检测癌细胞凋 亡比率;采用SABC免疫组化观察BIU-87细胞中bcl-2的表达变化。 结果As2O3可有效地抑制BIU-87细胞的体外生长(P<0.05),并具有时间及浓度依赖性的特点。经 4μmol/LAs2O3作用后,癌细胞DNA合成抑制率为55.64%。部分膀胱癌细胞体积缩小、核固缩、染色质核 膜下聚集,呈凋亡形态学改变,凋亡比例与As2O3作用时间呈正相关(P<0.05)。BIU-87细胞中bcl-2的表 达显著降低(P<0.05)。 结论As2O3通过下调癌细胞bcl-2基因表达、抑制癌细胞DNA合成等机制可显著诱导膀胱癌细胞凋亡, 为有效地防治膀胱癌复发提供了新的手段。

  14. Clinical Effects of Arsenic Trioxide by Slowing-intravenous Infusion on Acute Promyelocyte Leukemia

    Institute of Scientific and Technical Information of China (English)

    Jin Zhou; Ran Meng; Bao-feng Yang

    2005-01-01

    @@ Although As2O3 is effective in the treatment of acute promyelocytic leukemia (APL), some side effects, such as leukocytosis which can increase the incidence of cerebral hemorrhage and early death rate, often occur during the early stage of As2O3 treatment. In this paper, the advantages of continuously slow intravenous As2O3 infusion on relieving leukocytosis and decreasing the incidence of cerebral hemorrhage and early death rate were observed clinically.

  15. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-10-04

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

  16. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Lymphoma or Leukemia

    Science.gov (United States)

    2013-01-31

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  17. Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

    Science.gov (United States)

    2016-07-08

    Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Childhood Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm

  18. Mechanism of apoptosis of human osteosarcoma M-G63 induced by arsenic trioxide

    Institute of Scientific and Technical Information of China (English)

    XIAO Tao; LI Kang-hua; FANG Jian-zhen; WANG Wan-chun; LI Gui-yuan

    2005-01-01

    Objective To observe the apoptosis of osteosarcoma MG-63 cells induced by As2O3 and to explore its possible mechanisms. Methods The flowcytometric analysis and transmission electronmicroscope were performed to investigate the inducing apoptosis and inhibitative of As2O3 on osteosarcoma MG-63 cells. In order to study mechanism of apoptosis in MG-63 cells treated with As2 O3, microarray was performed. The down-regulated gene was confirmed by RT-PCR, Northern-blotting. Results After treated with As2O3, hypodiploid peak before G0/G1 phase was observed in MG-63 cells through FCM analysis. Loss of microvilli, condensation and fragmentation of nuclear chromatin, condensation of cytoplasmic organelles, dilatation of the endoplasmic reticulum shrinkage of cells and alterations in cell membranes and apoptosis bodies which were observed in MG-63 cells treated with As2O3 by transmission electronmicroscope. The results of microarray show that As2 O3 induced MG-63 cell apoptosis involves down-regulation of IEX-1 and the down-regulated gene is confirmed by RT-PCR and Northern-blotting.Conclusion The results show that As2 O3 selectively inhibits growth of the solid tumor MG-63 cells by triggering apoptosis and indicates MG-63 induced by As2O3 cell apoptosis may through the IEX-1 pathway.

  19. Transcriptome Profiling of Wheat Seedlings following Treatment with Ultrahigh Diluted Arsenic Trioxide

    Directory of Open Access Journals (Sweden)

    Ilaria Marotti

    2014-01-01

    Full Text Available Plant systems are useful research tools to address basic questions in homeopathy as they make it possible to overcome some of the drawbacks encountered in clinical trials (placebo effect, ethical issues, duration of the experiment, and high costs. The objective of the present study was to test the hypothesis whether 7-day-old wheat seedlings, grown from seeds either poisoned with a sublethal dose of As2O3 or unpoisoned, showed different significant gene expression profiles after the application of ultrahigh diluted As2O3 (beyond Avogadro’s limit compared to water (control. The results provided evidence for a strong gene modulating effect of ultrahigh diluted As2O3 in seedlings grown from poisoned seeds: a massive reduction of gene expression levels to values comparable to those of the control group was observed for several functional classes of genes. A plausible hypothesis is that ultrahigh diluted As2O3 treatment induced a reequilibration of those genes that were upregulated during the oxidative stress by bringing the expression levels closer to the basal levels normally occurring in the control plants.

  20. Morphological and functional changes of mitochondria in apoptotic esophageal carcinoma cells induced by arsenic trioxide

    Institute of Scientific and Technical Information of China (English)

    Zhong-Ying Shen; Jian Shen; Qiao-Shan Li; Cai-Yun Chen; Jiong-Yu Chen; Yi Zeng

    2002-01-01

    AIM: To demonstrate that mitochondrial morphological andfunctional changes are an important intermediate link in thecourse of apoptosis in esophageal carcinoma cells inducedby As2O3.METHODS: The esophageal carcinoma cell line SHEEC1,established in our laboratory, was cultured in 199 growthmedium, supplemented with 100mL@ L-1 calf serum and3 mol@L-1 As2O3( the same below). After 2, 4, 6, 12, 24 hof drug adding, the SHEEC1 cells were collected for light-and electron-microscopic examination. The mitochondriawere labeled by Rhodamine fluorescence probe and thefluorescence intensity of the mitochondria was measured byflow cytometer and cytofluorimetric analysis. Further, themitochondrial transmembrane potential ( MTP, ΔΨm )change was also calculated.RESULTS: The mitochondrial morphological change afteradding As2O3 could be divided into three stages. In theearly-stage (2-6h) after adding As2O3, an adaptiveproliferation of mitochondria appeared; in the mid-stage (6-12 h ) e degenerative change was observed; and in the late-stage (12-24 h ) the mitochondria swelled with outermembrana broken down and then calls death with apoptoticchanges of nucleus. The functional change of themitochondria indicated by fluorescent intensity, whichreflected the MTP status of mitochondria, was in accordancewith morphological change of the mitochondria. Thefluorescent intensity increased at early-stage, declined inmid-stage and decreased to the lowest in the late@ stage. 24h after As2O3 adding, the cell nucleus showed typicalapoptotic changes.CONCLUSION: Under the inducement of As2O3, the earlyapoptotic changes of SHEEC1 cells were the apparentmorphological and functional changes of mitochondria,afterwards the nucleus changes followed. lt is consideredthat changes of mitochondria are an important intermediatelink in the course of apoptosis of esophageal carcinomacalls induced by As2O3.

  1. Application of molybdenum trioxide in polymer light-emitting diodes

    OpenAIRE

    Shin, Y.S.

    2012-01-01

    The thesis investigates the application of molybdenum trioxide (MoO3-x) as hole injection layers (HILs) in polymeric light-emitting-diodes (PLEDs). Recent application of metal oxides into the PLED architecture has been motivated by the benefits of enhanced device performances, as well as, for the protection against the intrusion of oxygen and water into PLEDs. In this thesis, the performance of MoO3-x HILs in PLEDs is investigated by fabricating ITO/MoO3-x/TFB/F8BT/Ca/Al electroluminescent de...

  2. Raman study of thermochromic phase transition in tungsten trioxide nanowires

    Science.gov (United States)

    Lu, Dong Yu; Chen, Jian; Chen, Huan Jun; Gong, Li; Deng, Shao Zhi; Xu, Ning Sheng; Liu, Yu Long

    2007-01-01

    Tungsten trioxide (WO3) nanowires were synthesized by thermal evaporation of tungsten powder in two steps: tungsten suboxide (WO3-x) nanowires were synthesized, and then oxidized in O2 ambient and transformed into WO3 nanowires. Raman spectroscopy was applied to study the thermochromic phase transition of one-dimensional WO3 nanowires. From the temperature dependence of the characteristic mode at 33cm-1 in WO3, the phase transition temperature was determined. It was found that the phase transition of WO3 nanowires was reversible and the phase transition temperatures were even lower than that of WO3 nanopowder.

  3. In vitro and in vivo bioassay applied to uranium trioxide

    International Nuclear Information System (INIS)

    The aim of the present research is to suggest an in-vitro methodology, which can be used to characterize the physico-chemical properties of any sample of UO3 under investigation and to validate the results by in-vivo experiments in order to categorize it within the transferability classes defined by the International Commission on Radiological Protection. Thus three in vitro tests, one chemical and two cellular, were developed to determine the solubility of uranium trioxide in various solvents or biological environments and to shed light on the dissolution mechanisms. The inhalations were performed on rats

  4. Poisoning by coal smoke containing arsenic and fluoride

    Energy Technology Data Exchange (ETDEWEB)

    An, D.; He, Y.G.; Hu, Q.X. [Guizhou Sanitary and Epidemiological Station, Guiyang (China)

    1997-02-01

    An investigation was made into a disease involving skin pigmentation, keratosis of the hands and feet, dental discoloration, and generalized bone and joint pain, stiffness and rigidity, in the village of Bazhi, Zhijin County, Ghizhou Province, People`s Republic of China. Measurements were made of the arsenic and fluoride levels of coal, water, air, food, urine and hair in Bazhi and a control village, Xinzhai, in which coal with a low arsenic content was used. Up to 188 people, including children, in Bazhi and 752 in Xinzhai, were examined for the presence of chronic arsenium, skeletal fluorosis, dental fluorosis and electrocardiogram abnormalities. The coal in Bazhi was found to contain high levels of arsenic and fluoride resulting, after burning in homes without an adequate chimney systems, in pollution of air and food with arsenic and fluoride. The coal in Xinzhai did not cause arsenic pollution but did produce a higher level of fluoride pollution. It was concluded that the endemic disease in Bazhi was caused by pollution by coal smoke containing arsenic and fluoride. It is suggested that arsenic may act synergistically with fluoride so that a lower level of fluoride may produce fluoride toxicity with dental and skeletal fluorosis.

  5. Cryptic exposure to arsenic.

    Science.gov (United States)

    Rossy, Kathleen M; Janusz, Christopher A; Schwartz, Robert A

    2005-01-01

    Arsenic is an odorless, colorless and tasteless element long linked with effects on the skin and viscera. Exposure to it may be cryptic. Although human intake can occur from four forms, elemental, inorganic (trivalent and pentavalent arsenic) and organic arsenic, the trivalent inorganic arsenicals constitute the major human hazard. Arsenic usually reaches the skin from occupational, therapeutic, or environmental exposure, although it still may be employed as a poison. Occupations involving new technologies are not exempt from arsenic exposure. Its acute and chronic effects are noteworthy. Treatment options exist for arsenic-induced pathology, but prevention of toxicity remains the main focus. Vitamin and mineral supplementation may play a role in the treatment of arsenic toxicity.

  6. Cryptic exposure to arsenic

    Directory of Open Access Journals (Sweden)

    Rossy Kathleen

    2005-01-01

    Full Text Available Arsenic is an odorless, colorless and tasteless element long linked with effects on the skin and viscera. Exposure to it may be cryptic. Although human intake can occur from four forms, elemental, inorganic (trivalent and pentavalent arsenic and organic arsenic, the trivalent inorganic arsenicals constitute the major human hazard. Arsenic usually reaches the skin from occupational, therapeutic, or environmental exposure, although it still may be employed as a poison. Occupations involving new technologies are not exempt from arsenic exposure. Its acute and chronic effects are noteworthy. Treatment options exist for arsenic-induced pathology, but prevention of toxicity remains the main focus. Vitamin and mineral supplementation may play a role in the treatment of arsenic toxicity.

  7. Arsenic: the forgotten poison?

    Science.gov (United States)

    Barton, E N; Gilbert, D T; Raju, K; Morgan, O S

    1992-03-01

    Chronic arsenic poisoning is an uncommon cause of peripheral neuropathy in Jamaica. A patient with this disorder is described. The insidious nature of chronic arsenic poisoning, with its disabling complications, is emphasised.

  8. Summary of four scientific studies on Arsenicum album high dilution effect against Arsenic intoxication in mice

    Directory of Open Access Journals (Sweden)

    Laurence Terzan

    2012-09-01

    arsenic intoxication. Results: Compared to controls, Arsenicum album 30cH induced a significant decrease in accumulation of arsenic in 4 tissues namely liver, spleen, kidney and testis in intoxicated mice. In addition, both Arsenicum album 6cH, 30cH and 200cH reduced chromosome aberrations, sperm head abnormality frequencies and activities of acid and alkaline phosphatases, aspartate and alanine aminotransferases and lipid peroxidation, while mitotic index and activities of glutathione, catalase and succinate dehydrogenase were increased compared to controls. Conclusion: Altogether, theses results provide evidence of protective potentials of the Arsenicum album dilution against acute and chronic arsenic intoxication in mice. They also offer a new hypothesis that the mechanism of the homeopathic dilution could act through regulation of expression of certain genes. This explanation seems to be plausible because all biomarker tests are regulated by specific genetic regulatory mechanisms [6]. keywords: Arsenicum album, arsenic intoxication, enzymatic and biomarker toxicity. References: [1] WHO. WHO Guidelines for Drinking Water Quality, Vol. 2, 2nd edition. Geneva: WHO, 1996, 940–9. [2] Cazin JC, Cazin M, Gaborit JL, Chaoui A, Boiron J, Belon P, et al. A study of the effect of decimal and centesimal dilutions of arsenic on the retention and mobilization of arsenic in the rat. Hum Toxicol 1987;6:315–20. [3] Mitra K, Kundu SN, Khuda-Bukhsh AR. Efficacy of a potentized homoeopathic drug (Arsenicum Album-30 in reducing toxic effects produced by of arsenic trioxide in mice. I. On rate accumulation of arsenic in certain vital organs. Comp Ther Med 1998;6:178–84. [4] Pathikrit Banerjee. Evidences of Protective Potentials of Microdoses of Ultra-high Diluted Arsenic Trioxide in Mice Receiving Repeated Injections of Arsenic Trioxide. eCAM 2009; 1-10. [5] Pathikrit Banerjee, Comparative Efficacy of Two Microdoses of a

  9. Arsenic pollution sources.

    Science.gov (United States)

    Garelick, Hemda; Jones, Huw; Dybowska, Agnieszka; Valsami-Jones, Eugenia

    2008-01-01

    Arsenic is a widely dispersed element in the Earth's crust and exists at an average concentration of approximately 5 mg/kg. There are many possible routes of human exposure to arsenic from both natural and anthropogenic sources. Arsenic occurs as a constituent in more than 200 minerals, although it primarily exists as arsenopyrite and as a constituent in several other sulfide minerals. The introduction of arsenic into drinking water can occur as a result of its natural geological presence in local bedrock. Arsenic-containing bedrock formations of this sort are known in Bangladesh, West Bengal (India), and regions of China, and many cases of endemic contamination by arsenic with serious consequences to human health are known from these areas. Significant natural contamination of surface waters and soil can arise when arsenic-rich geothermal fluids come into contact with surface waters. When humans are implicated in causing or exacerbating arsenic pollution, the cause can almost always be traced to mining or mining-related activities. Arsenic exists in many oxidation states, with arsenic (III) and (V) being the most common forms. Similar to many metalloids, the prevalence of particular species of arsenic depends greatly on the pH and redox conditions of the matrix in which it exists. Speciation is also important in determining the toxicity of arsenic. Arsenic minerals exist in the environment principally as sulfides, oxides, and phosphates. In igneous rocks, only those of volcanic origin are implicated in high aqueous arsenic concentrations. Sedimentary rocks tend not to bear high arsenic loads, and common matrices such as sands and sandstones contain lower concentrations owing to the dominance of quartz and feldspars. Groundwater contamination by arsenic arises from sources of arsenopyrite, base metal sulfides, realgar and orpiment, arsenic-rich pyrite, and iron oxyhydroxide. Mechanisms by which arsenic is released from minerals are varied and are accounted for by

  10. Quantifying synergistic mutual information

    CERN Document Server

    Griffith, Virgil

    2012-01-01

    Quantifying cooperation among random variables in predicting a single target random variable is an important problem in many biological systems with 10s to 1000s of co-dependent variables. We review the prior literature of information theoretical measures of synergy and introduce a novel synergy measure, entitled *synergistic mutual information* and compare it against the three existing measures of cooperation. We apply all four measures against a suite of binary circuits to demonstrate our measure alone quantifies the intuitive concept of synergy across all examples.

  11. Arsenic content in Portland cement: A literature review

    Directory of Open Access Journals (Sweden)

    Tenorio de Franca Talita

    2010-01-01

    Full Text Available Portland cement (PC is a hydraulic binding material widely used in the building industry. The main interest in its use in dentistry is focused on a possible alternative to mineral trioxide aggregate (MTA because PC is less expensive and is widely available. In dentistry, PC has been used in dental procedures such as pulpotomy, pulp capping, repair of root perforation and root-end filling. The purpose of this article is review the dental literature about the PC, its composition with special attention to arsenic content, properties, and application in dentistry. A bibliographic research was performed in Bireme, PubMed, LILACS and Scopus data bases looking for national and international studies about the PC composition, properties and clinical use. It was observed that PC has favorable biological properties very similar to those of MTA. The PC has shown good cell proliferation induction with formation of a monolayer cell, satisfactory inflammatory response, inhibitory effect of prostaglandin and antimicrobial effect. Studies have shown that PC is not cytotoxic, stimulates the apposition of reparative dentin and permits cellular attachment and growth. Regarding arsenic presence, its levels and release are low. PC has physical, chemical and biological properties similar to MTA. Arsenic levels and release are low, therefore, unable to cause toxic effects.

  12. Arsenic compounds toxic to rice

    Energy Technology Data Exchange (ETDEWEB)

    Epps, E.A.; Sturgis, M.B.

    1939-01-01

    A study has been made of the kinds of arsenic compounds that may be toxic to rice and of means for correcting the toxicity. Some of the arsenic compounds in flooded soils are reduced, with consequent increase in soluble arsenic content of the soil and decrease in total arsenic content due to liberation of gaseous compounds of arsenic. It was demonstrated that some of the arsenic was lost as arsine. Many of the naturally-occurring compounds of arsenic are not attacked by the micro-organisms and do not become more soluble. Additions of sulfur to soils containing toxic amounts of arsenic decreased the amount of soluble arsenic in the soil.

  13. Arsenic removal from water

    Science.gov (United States)

    Moore, Robert C.; Anderson, D. Richard

    2007-07-24

    Methods for removing arsenic from water by addition of inexpensive and commonly available magnesium oxide, magnesium hydroxide, calcium oxide, or calcium hydroxide to the water. The hydroxide has a strong chemical affinity for arsenic and rapidly adsorbs arsenic, even in the presence of carbonate in the water. Simple and commercially available mechanical methods for removal of magnesium hydroxide particles with adsorbed arsenic from drinking water can be used, including filtration, dissolved air flotation, vortex separation, or centrifugal separation. A method for continuous removal of arsenic from water is provided. Also provided is a method for concentrating arsenic in a water sample to facilitate quantification of arsenic, by means of magnesium or calcium hydroxide adsorption.

  14. Removal of cobalt from zinc sulphate solution using rude antimony trioxide as additive

    Institute of Scientific and Technical Information of China (English)

    戴军; 王德全; 姜澜; 金曼

    2002-01-01

    The process of cobalt removal from zinc sulphate solution using rude antimony trioxide as an additive was investigated. The rude antimony trioxide was produced in treatment of copper and lead anode mud and its main components are antimony trioxide, antimony arsenate and lead antimonate. Using the rude antimony trioxide as the additive of cobalt removal can not only decrease operation cost of purification but also find out a new way for utilization of the rude antimony trioxide. The effects of temperature, dosage of zinc dust, the rude antimony trioxide, copper ion and solution pH on removal of cobalt were studied. And experimental data using the rude Sb2O3 as additive were compared with those using Sb2O3. The results indicate that using rude Sb2O3 as additive, cobalt concentration in solution could be decreased from 24mg/L to below 1mg/L under about the same conditions as using Sb2O3.

  15. The Synergistic Engineering Environment

    Science.gov (United States)

    Cruz, Jonathan

    2006-01-01

    The Synergistic Engineering Environment (SEE) is a system of software dedicated to aiding the understanding of space mission operations. The SEE can integrate disparate sets of data with analytical capabilities, geometric models of spacecraft, and a visualization environment, all contributing to the creation of an interactive simulation of spacecraft. Initially designed to satisfy needs pertaining to the International Space Station, the SEE has been broadened in scope to include spacecraft ranging from those in low orbit around the Earth to those on deep-space missions. The SEE includes analytical capabilities in rigid-body dynamics, kinematics, orbital mechanics, and payload operations. These capabilities enable a user to perform real-time interactive engineering analyses focusing on diverse aspects of operations, including flight attitudes and maneuvers, docking of visiting spacecraft, robotic operations, impingement of spacecraft-engine exhaust plumes, obscuration of instrumentation fields of view, communications, and alternative assembly configurations. .

  16. Acute arsenic poisoning: absence of polyneuropathy after treatment with 2,3-dimercaptopropanesulphonate (DMPS).

    Science.gov (United States)

    Moore, D F; O'Callaghan, C A; Berlyne, G; Ogg, C S; Davies, H A; House, I M; Henry, J A

    1994-01-01

    Two men aged 19 and 21 years ingested 1 g and 4 g respectively from 3 kg of a white crystalline powder that they thought was a substance of abuse. It was later identified as almost pure arsenic trioxide. Both had nausea and vomiting and one developed acute renal failure. Each was treated with 2,3-dimercaptopropanesulphonate (DMPS), and made a full recovery with no evidence of prolonged renal or neurological impairment. The DMPS-arsenic complex is probably associated with lower penetration into the CNS and as a consequence treatment with DMPS may result in lower acute and chronic neurotoxicity than treatment with the currently standard recommended chelating agent dimercaprol (British Anti-Lewisite; BAL). PMID:8089687

  17. Construction of a modular arsenic resistance operon in E. coli and the production of arsenic nanoparticles

    Directory of Open Access Journals (Sweden)

    Matthew Charles Edmundson

    2015-10-01

    Full Text Available Arsenic is a widespread contaminant of both land and water around the world. Current methods of decontamination such as phytoremediation and chemical adsorbents can be resource and time intensive, and may not be suitable for some areas such as remote communities where cost and transportation are major issues. Bacterial decontamination, with strict controls preventing environmental release, may offer a cost-effective alternative or provide a financial incentive when used in combination with other remediation techniques. In this study we have produced E. coli strains containing arsenic resistance genes from a number of sources, overexpressing them and testing their effects on arsenic resistance. While the lab E. coli strain JM109 (the wild-type is resistant up to 20 mM sodium arsenate the strain containing our plasmid pEC20 is resistant up to 80 mM. When combined with our construct pArsRBCC arsenic-containing nanoparticles were observed at the cell surface; the elements of pEC20 and pArsRBCC were therefore combined in a modular construct, pArs, in order to evaluate the roles and synergistic effects of the components of the original plasmids in arsenic resistance and nanoparticle formation. We also investigated the use of introducing the lac operator in order to more tightly control expression from pArs. We demonstrate that our strains are able to reduce toxic forms of arsenic into stable, insoluble metallic As(0, providing one way to remove arsenate contamination, and which may also be of benefit for other heavy metals.

  18. Environmental Source of Arsenic Exposure

    OpenAIRE

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-01-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a ...

  19. THE SYNERGISTIC EFFECT OF HYBRID FLAME RETARDANTS ON PYROLYSIS BEHAVIOUR OF HYBRID COMPOSITE MATERIALS

    Directory of Open Access Journals (Sweden)

    M. T. ALBDIRY

    2012-06-01

    Full Text Available The aim of this investigation is to comprehensively understand the polymeric composite behavior under direct fire sources. The synergistic effects of hybrid flame retardant material on inhabiting the pyrolysis of hybrid reinforced fibers, woven roving (0°- 45° carbon and kevlar (50/50 wt/wt, and an araldite resin composites were studied. The composites were synthesised and coated primarily by zinc borate (2ZnO.3B2O3.3.5H2O and modified by antimony trioxide (Sb2O3 with different amounts (10-30 wt% of flame retardant materials. In the experiments, the composite samples were exposed to a direct flame source generated by oxyacetylene flame (~3000ºC at variable exposure distances of 10-20 mm. The synergic flame retardants role of antimony trioxide and zinc borate on the composite surface noticeably improves the flame resistance of the composite which is attributed to forming a protective mass and heat barrier on the composite surface and increasing the melt viscosity.

  20. Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

    International Nuclear Information System (INIS)

    Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a ‘2-hit’ paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet (± arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: ► Characterizes a mouse model of arsenic enhanced NAFLD. ► Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. ► This effect is associated with increased inflammation.

  1. Arsenic compounds and cancer.

    Science.gov (United States)

    Axelson, O

    1980-01-01

    Exposure to arsenic compounds has been epidemiologically associated with various types of cancers, particularly cancer of the lung among copper smelters and pesticide workers, whereas skin cancers and liver angiosarcomas have been associated with ingestion of arsenic for treatment of skin disorders, especially psoriasis. Attempts to reproduce cancer in animals have been mainly unsuccessful, however. Experimental evidence suggests that arsenic inhibits DNA repair; this might help to explain the somewhat conflicting observations from epidemiologic studies and animal experiments with regard to carcinogenicity, and perhaps also cardiovascular morbidity related to arsenic exposure. PMID:7463514

  2. Arsenic poisoning in cattle

    Energy Technology Data Exchange (ETDEWEB)

    Reagor, J.C.

    Reports of heavy metal intoxication submitted to the Texas Veterinary Medical Diagnostic Laboratory indicate that arsenic is the most common heavy metal intoxicant in Texas. The most frequent sources of arsenic are compounds used as herbicides and cotton defoliants. The misuse of these compounds and subsequent intoxication of cattle is discussed in this paper. 8 references, 1 table.

  3. Arsenic in Food

    Science.gov (United States)

    ... Biologics Animal & Veterinary Cosmetics Tobacco Products Food Home Food Foodborne Illness & Contaminants Metals Arsenic Share Tweet Linkedin Pin it More ... and previous or current use of arsenic-containing pesticides. Are there ... compounds in water, food, air, and soil: organic and inorganic (these together ...

  4. Mineral trioxide aggregate: a review of physical properties.

    Science.gov (United States)

    Malhotra, Neeraj; Agarwal, Antara; Mala, Kundabala

    2013-02-01

    The purpose of this two-part series is to review the composition, properties, products, and clinical aspects of mineral trioxide aggregate (MTA) materials. Electronic search of scientific papers from January 1991 to May 2010 was accomplished using PubMed and MedLine search engines to include relevant scientific citations from the peer-reviewed journals published in English. MTA is a refined form of the parent compound, Portland cement (PC). It demonstrates a strong biocompatible nature owing to the high pH and its ability to form hydroxyapatite. MTA materials provide a better seal than traditional endodontic materials as observed in dye leakage, fluid filtration, protein leakage, and bacterial penetration leakage studies, and it has been recognized as a bioactive material. Currently a variety of MTA commercial products are available, including Proroot Gray MTA and White MTA both from DENTSPLY Tulsa Dental Specialties (www.DENTSPLY.com), and MTA Angelus (Angelus,www.angelus.ind.br). Although these materials are indicated for various dental uses/applications, long-term in-vivo clinical studies are still needed to claim the same. This first of this series highlights and discusses the composition, physical, and/or chemical properties of MTA. A subsequent article will offer an overview of the material aspect (commercial products) and clinical considerations for MTA materials. PMID:23627406

  5. Mineral trioxide aggregate induces osteoblastogenesis via Atf6

    Directory of Open Access Journals (Sweden)

    Toyonobu Maeda

    2015-06-01

    Full Text Available Mineral trioxide aggregate (MTA has been recommended for various uses in endodontics. To understand the effects of MTA on alveolar bone, we examined whether MTA induces osteoblastic differentiation using MC3T3-E1 cells. MTA enhanced mineralization concomitant with alkaline phosphatase activity in a dose- and time-dependent manner. MTA increased production of collagens (Type I and Type III and matrix metalloproteinases (MMP-9 and MMP-13, suggesting that MTA affects bone matrix remodeling. MTA also induced Bglap (osteocalcin but not Bmp2 (bone morphogenetic protein-2 mRNA expression. We observed induction of Atf6 (activating transcription factor 6, an endoplasmic reticulum (ER stress response transcription factor mRNA expression and activation of Atf6 by MTA treatment. Forced expression of p50Atf6 (active form of Atf6 markedly enhanced Bglap mRNA expression. Chromatin immunoprecipitation assay was performed to investigate the increase in p50Atf6 binding to the Bglap promoter region by MTA treatment. Furthermore, knockdown of Atf6 gene expression by introduction of Tet-on Atf6 shRNA expression vector abrogated MTA-induced mineralization. These results suggest that MTA induces in vitro osteoblastogenesis through the Atf6–osteocalcin axis as ER stress signaling. Therefore, MTA in endodontic treatment may affect alveolar bone healing in the resorbed region caused by pulpal infection.

  6. Emissions of sulfur trioxide from coal-fired power plants

    Energy Technology Data Exchange (ETDEWEB)

    R.K. Srivastava; C.A. Miller; C. Erickson; R. Jambhekar [U.S. Environmental Protection Agency, Research Triangle Park, NC (United States). Office of Research and Development, National Risk Management Research Laboratory, Air Pollution Prevention and Control Division

    2004-06-01

    Emissions of sulfur trioxide (SO{sub 3}) are a key component of plume opacity and acid deposition. These emissions should therefore to be low enough to not cause opacity violations and acid deposition. Generally, a small fraction of sulfur (S) in coal is converted to SO{sub 3} in coal-fired combustion devices such as electric utility boilers. The emissions of SO{sub 3} from such a boiler depend on coal S content, combustion conditions, flue gas characteristics, and air pollution devices being used. It is well known that the catalyst used in the selective catalytic reduction (SCR) technology for nitrogen oxides control oxidizes a small fraction of sulfur dioxide in the flue gas to SO{sub 3}. The extent of this oxidation depends on the catalyst formulation and SCR operating conditions. Gas-phase SO{sub 3} and sulfuric acid, on being quenched in plant equipment (e.g., air preheater and wet scrubber), result in fine acidic mist, which can cause increased plume opacity and undesirable emissions. Recently, such effects have been observed at plants firing high-S coal and equipped with SCR systems and wet scrubbers. This paper investigates the factors that affect acidic mist production in coal-fired electric utility boilers and discusses approaches for mitigating emission of this mist. 50 refs., 8 figs., 1 tab.

  7. Binational Arsenic Exposure Survey: Methodology and Estimated Arsenic Intake from Drinking Water and Urinary Arsenic Concentrations

    Science.gov (United States)

    Roberge, Jason; O’Rourke, Mary Kay; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Burgess, Jefferey L.; Harris, Robin B.

    2012-01-01

    The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic) and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L) whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001), urinary inorganic arsenic concentration (p < 0.001), and urinary sum of species (p < 0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated. PMID:22690182

  8. Binational Arsenic Exposure Survey: Methodology and Estimated Arsenic Intake from Drinking Water and Urinary Arsenic Concentrations

    Directory of Open Access Journals (Sweden)

    Robin B. Harris

    2012-03-01

    Full Text Available The Binational Arsenic Exposure Survey (BAsES was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001, urinary inorganic arsenic concentration (p < 0.001, and urinary sum of species (p < 0.001. Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated.

  9. EFFECTS OF ADDROGRAPHIS PANICULATA (NEES. ON ARSENIC- INDUCED ALTERED GLUCOSE HOMEOSTASIS AND OXIDATIVE IMPAIRMENT IN PANCREAS OF SWISS MICE

    Directory of Open Access Journals (Sweden)

    MANDAVA V. RAO

    2007-01-01

    Full Text Available The effect of Andrographis paniculata (Nees. on arsenic-induced changes in biochemical and cellular antioxident sytem was studies in adult female mice. Daily oral administration of arsenic trioxide (0.5 and 1.0mg/kg b.w for 30days induced a significant increase in blood glucose level which was associated with impaired glucose tolrence. Arsenic treatment also resulted in elevated level panreatic tissue specific makers such as activities of amylase and lipase in serum indicating pancreatic dysfunction. Interestingly, this biochemical dysfuntion was accompanied by a marked dose related enchancement of lipid peroxidation indicating significant induction of oxidative damage. Additional evidence such as deletion in reduced gluatathione levels and alterations in enzymic antioxidant defences like superoxide dismutase, catalase and glutathione peroxidase in pancreas suggested induction of oxidative stress. Concomitant administration of Adrographis paniculata (50 mg/kg b.w. with arsenic significant restored all these parameters. These results suggest that Adrographis paniculata is capable to reducing arsenic-induce cellular oxidative and inflammatory changes in pancreas.

  10. USEPA Arsenic Demonstration Program

    Science.gov (United States)

    The presentation provides background information on the USEPA arsenic removal program. The summary includes information on the history of the program, sites and technology selected, and a summary of the data collected from two completed projects.

  11. EXAFS study on arsenic species and transformation in arsenic hyperaccumulator

    Institute of Scientific and Technical Information of China (English)

    HUANG; Zechun; CHEN; Tongbin; LEI; Mei; HU; Tiandou; HUANG

    2004-01-01

    Synchrotron radiation extended X-ray absorption fine structure (SR EXAFS) was employed to study the transformation of coordination environment and the redox speciation of arsenic in a newly discovered arsenic hyperaccumulator, Cretan brake (Pteris cretica L. var nervosa Thunb). It showed that the arsenic in the plant mainly coordinated with oxygen, except that some arsenic coordinated with S as As-GSH in root. The complexation of arsenic with GSH might not be the predominant detoxification mechanism in Cretan brake. Although some arsenic in root presented as As(V) in Na2HAsO4 treatments, most of arsenic in plant presented as As(III)-O in both treatments, indicating that As(V) tended to be reduced to As(III) after it was taken up into the root, and arsenic was kept as As(III) when it was transported to the above-ground tissues. The reduction of As(V) primarily proceeded in the root.

  12. Use of a matrix for apexification procedure with mineral trioxide aggregate

    Directory of Open Access Journals (Sweden)

    Khatavkar Roheet

    2010-01-01

    Full Text Available This articles describes a technique for placement of a matrix barrier prior to use of mineral trioxide aggregate (MTA as an artificial root-end barrier. The technique also demonstrates the use of a delivery system utilizing large-bore needles for the predictable and precise placement of the barrier materials at the apex of the tooth.

  13. Reactions of functionalized alkenes with sulfur trioxide; mechanistic and synthetic aspects. Doctoral thesis

    Energy Technology Data Exchange (ETDEWEB)

    Schonk, R.M.

    1993-01-07

    In the thesis mechanistic studies on the sulfonation of mono-functionalized alkenes, viz. phenylalkenes, naphthylalkenes, alkenoic acids, alkadienes and cycloalkylidenes, mainly with sulfur trioxide are described. The main objective of the studies is to determine the effect of the substituents at the alkene moiety on the formation of the beta-sultones and carbyl sulfates and on their chemistry.

  14. Arsenic and dichlorvos: Possible interaction between two environmental contaminants.

    Science.gov (United States)

    Flora, Swaran J S

    2016-05-01

    Metals are ubiquitously present in the environment and pesticides are widely used throughout the world. Environmental and occupational exposure to metal along with pesticide is an area of great concern to both the public and regulatory authorities. Our major concern is that combination of these toxicant present in environment may elicit toxicity either due to additive or synergistic interactions or 'joint toxic actions' among these toxicants. It poses a rising threat to human health. Water contamination particularly ground water contamination with arsenic is a serious problem in today's scenario since arsenic is associated with several kinds of health problems, such arsenic associated health anomalies are commonly called as 'Arsenism'. Uncontrolled use and spillage of pesticides into the environment has resulted in alarming situation. Moreover serious concerns are being addressed due to their persistence in the environmental matrices such as air, soil and surface water runoff resulting in continuous exposure of these harmful chemicals to human beings and animals. Bio-availability of these environmental toxicants has been enhanced much due to anthropological activities. Dreadfully very few studies are available on combined exposures to these toxicants on the animal or human system. Studies on the acute and chronic exposure to arsenic and DDVP are well reported and well defined. Arsenic is a common global ground water contaminant while dichlorvos is one of the most commonly and widely employed organophosphate based insecticide used in agriculture, horticulture etc. There is thus a real situation where a human may get exposed to these toxicants while working in a field. This review highlights the individual and combined exposure to arsenic and dichlorvos on health. PMID:27049126

  15. Characterization of arsenic resistant bacteria from arsenic rich groundwater of West Bengal, India.

    Science.gov (United States)

    Sarkar, Angana; Kazy, Sufia K; Sar, Pinaki

    2013-03-01

    Sixty-four arsenic (As) resistant bacteria isolated from an arsenic rich groundwater sample of West Bengal were characterized to investigate their potential role in subsurface arsenic mobilization. Among the isolated strains predominance of genera Agrobacterium/Rhizobium, Ochrobactrum and Achromobacter which could grow chemolitrophically and utilize arsenic as electron donor were detected. Higher tolerance to As(3+) [maximum tolerable concentration (MTC): ≥10 mM], As(5+) (MTC: ≥100 mM) and other heavy metals like Cu(2+), Cr(2+), Ni(2+) etc. (MTC: ≥10 mM), presence of arsenate reductase and siderophore was frequently observed among the isolates. Ability to produce arsenite oxidase and phosphatase enzyme was detected in 50 and 34 % of the isolates, respectively. Although no direct correlation among taxonomic identity of bacterial strains and their metabolic abilities as mentioned above was apparent, several isolates affiliated to genera Ochrobactrum, Achromobacter and unclassified Rhizobiaceae members were found to be highly resistant to As(3+) and As(5+) and positive for all the test properties. Arsenate reductase activity was found to be conferred by arsC gene, which in many strains was coupled with arsenite efflux gene arsB as well. Phylogenetic incongruence between the 16S rRNA and ars genes lineages indicated possible incidence of horizontal gene transfer for ars genes. Based on the results we propose that under the prevailing low nutrient condition inhabitant bacteria capable of using inorganic electron donors play a synergistic role wherein siderophores and phosphatase activities facilitate the release of sediment bound As(5+), which is subsequently reduced by arsenate reductase resulting into the mobilization of As(3+) in groundwater. PMID:23238642

  16. Construction of a Modular Arsenic-Resistance Operon in E. coli and the Production of Arsenic Nanoparticles.

    Science.gov (United States)

    Edmundson, Matthew Charles; Horsfall, Louise

    2015-01-01

    Arsenic is a widespread contaminant of both land and water around the world. Current methods of decontamination such as phytoremediation and chemical adsorbents can be resource and time intensive, and may not be suitable for some areas such as remote communities where cost and transportation are major issues. Bacterial decontamination, with strict controls preventing environmental release, may offer a cost-effective alternative or provide a financial incentive when used in combination with other remediation techniques. In this study, we have produced Escherichia coli strains containing arsenic-resistance genes from a number of sources, overexpressing them and testing their effects on arsenic resistance. While the lab E. coli strain JM109 (the "wild-type") is resistant up to 20 mM sodium arsenate, the strain containing our plasmid pEC20 is resistant up to 80 mM. When combined with our construct pArsRBCC arsenic--containing nanoparticles were observed at the cell surface; the elements of pEC20 and pArsRBCC were therefore combined in a modular construct, pArs, in order to evaluate the roles and synergistic effects of the components of the original plasmids in arsenic resistance and nanoparticle formation. We have also investigated introducing the lac operator in order to more tightly control expression from pArs. We demonstrate that our strains are able to reduce toxic forms of arsenic into stable, insoluble metallic As(0), providing one way to remove arsenate contamination, and which may also be of benefit for other heavy metals.

  17. Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis

    Science.gov (United States)

    Biotransformation of inorganic arsenic (iAs) involves methylation catalyzed by arsenic (+3 oxidation state) methyltransferase (As3mt), yielding mono- , di- , and trimethylated arsenicals. To investigate the evolution of molecular mechanisms that mediate arsenic biotransformation,...

  18. Sources and circulation of water and arsenic in the Giant Mine, Yellowknife, NWT, Canada.

    Science.gov (United States)

    Clark, Ian D; Raven, Kenneth G

    2004-06-01

    Recovery of gold from arsenopyrite-hosted ore in the Giant Mine camp, Yellowknife, NWT, Canada, has left a legacy of arsenic contamination that poses challenges for mine closure planning. Seepage from underground chambers storing some 237,000 tonnes of arsenic trioxide dust, has As concentrations exceeding 4000 ppm. Other potential sources and sinks of As also exist. Sources and movement of water and arsenic are traced using the isotopes of water and sulphate. Mine waters (16 ppm As; AsV/AsIII approximately 150) are a mixture of two principal water sources--locally recharged, low As groundwaters (0.5 ppm As) and Great Slave Lake (GSL; 0.004 ppm As) water, formerly used in ore processing and discharged to the northwest tailings impoundment (NWTP). Mass balance with delta18O shows that recirculation of NWTP water to the underground through faults and unsealed drillholes contributes about 60% of the mine water. Sulphate serves to trace direct infiltration to the As2O3 chambers. Sulphate in local, low As groundwaters (0.3-0.6 ppm As; delta34SSO4 approximately 4% and delta18OSO4 approximately -10%) originates from low-temperature aqueous oxidation of sulphide-rich waste rock. The high As waters gain a component of 18O-enriched sulphate derived from roaster gases (delta18OSO4) = + 3.5%), consistent with their arsenic source from the As2O3 chambers. High arsenic in NWTP water (approximately 8 ppm As; delta18OSO4 = -2%) derived from mine water, is attenuated to close to 1 ppm during infiltration back to the underground, probably by oxidation and sorption by ferrihydrite.

  19. Arsenic in Cancer Treatment: Challenges for Application of Realgar Nanoparticles (A Minireview

    Directory of Open Access Journals (Sweden)

    Peter Baláž

    2010-06-01

    Full Text Available While intensive efforts have been made for the treatment of cancer, this disease is still the second leading cause of death in many countries. Metastatic breast cancer, late-stage colon cancer, malignant melanoma, multiple myeloma, and other forms of cancer are still essentially incurable in most cases. Recent advances in genomic technologies have permitted the simultaneous evaluation of DNA sequence-based alterations together with copy number gains and losses. The requirement for a multi-targeting approach is the common theme that emerges from these studies. Therefore, the combination of new targeted biological and cytotoxic agents is currently under investigation in multimodal treatment regimens. Similarly, a combinational principle is applied in traditional Chinese medicine, as formulas consist of several types of medicinal herbs or minerals, in which one represents the principal component, and the others serve as adjuvant ones that assist the effects, or facilitate the delivery, of the principal component. In Western medicine, approximately 60 different arsenic preparations have been developed and used in pharmacological history. In traditional Chinese medicines, different forms of mineral arsenicals (orpiment—As2S3, realgar—As4S4, and arsenolite—arsenic trioxide, As2O3 are used, and realgar alone is included in 22 oral remedies that are recognized by the Chinese Pharmacopeia Committee (2005. It is known that a significant portion of some forms of mineral arsenicals is poorly absorbed into the body, and would be unavailable to cause systemic damage. This review primary focuses on the application of arsenic sulfide (realgar for treatment of various forms of cancer in vitro and in vivo.

  20. Arsenic, Anaerobes, and Astrobiology

    Science.gov (United States)

    Stolz, J. F.; Oremland, R. S.; Switzer Blum, J.; Hoeft, S. E.; Baesman, S. M.; Bennett, S.; Miller, L. G.; Kulp, T. R.; Saltikov, C.

    2013-12-01

    Arsenic is an element best known for its highly poisonous nature, so it is not something one would associate with being a well-spring for life. Yet discoveries made over the past two decades have delineated that not only are some microbes resistant to arsenic, but that this element's primary redox states can be exploited to conserve energy and support prokaryotic growth ('arsenotrophy') in the absence of oxygen. Hence, arsenite [As(III)] can serve as an electron donor for chemo- or photo-autotrophy while arsenate [As(V)] will serve as an electron acceptor for chemo-heterotrophs and chemo-autotrophs. The phylogenetic diversity of these microbes is broad, encompassing many individual species from diverse taxonomic groups in the Domain Bacteria, with fewer representatives in the Domain Archaea. Speculation with regard to the evolutionary origins of the key functional genes in anaerobic arsenic transformations (arrA and arxA) and aerobic oxidation (aioB) has led to a disputation as to which gene and function is the most ancient and whether arsenic metabolism extended back into the Archaean. Regardless of its origin, robust arsenic metabolism has been documented in extreme environments that are rich in their arsenic content, such as hot springs and especially hypersaline soda lakes associated with volcanic regions. Searles Lake, CA is an extreme, salt-saturated end member where vigorous arsenic metabolism occurs, but there is no detectable sulfate-reduction or methanogenesis. The latter processes are too weak bio-energetically to survive as compared with arsenotrophy, and are also highly sensitive to the abundance of borate ions present in these locales. These observations have implications with respect to the search for microbial life elsewhere in the Solar System where volcanic-like processes have been operative. Hence, because of the likelihood of encountering dense brines in the regolith of Mars (formed by evapo-concentration) or beneath the ice layers of Europa

  1. Arsenic hyperaccumulator Pteris Vittata L. and its arsenic accumulation

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    An arsenic hyperaccumulator Pteris vittata L. (Chinese brake) was first discovered in China by means of field survey and greenhouse cultivation. Field survey showed that Chinese brake had large accumulating capacity to arsenic; the orders of arsenic content in different parts of the fern were as follows: leaves>leafstalks>roots, which is totally different from that of ordinary plants; bioaccumulation coefficients of the above ground parts of the fern decreased as a power function of soil arsenic contents. In the control of pot trials with normal unpolluted soil containing 9 mg/kg of arsenic, the bioaccumulation coefficients of the above ground parts and rhizoids of Chinese brake were as high as 71 and 80 respectively. Greenhouse cultivation in the contaminated soil from mining areas has shown that more than 1 times greater arsenic can be accumulated in the leaves of the fern than that of field samples with the largest content of 5070 mg/kg As on a dry matter basis. During greenhouse cultivation, arsenic content in the leaves of the fern increased linearly with time prolonging. Not only has Chinese brake extraordinary tolerance and accumulation to arsenic, but it grew rapidly with great biomass, wide distribution and easy adaptation to different environmental conditions as well. Therefore, it has great potential in future remediation of arsenic contamination. It also demonstrates important value for studies of arsenic physiology and biochemistry such as arsenic absorption, translocation and detoxification mechanisms in plants.

  2. The Role of Oxidative Stress in Gastrointestinal Tract Tissues Induced by Arsenic Toxicity in Cocks.

    Science.gov (United States)

    Guo, Ying; Zhao, Panpan; Guo, Guangyang; Hu, Zhibo; Tian, Li; Zhang, Kexin; Zhang, Wen; Xing, Mingwei

    2015-12-01

    Arsenic (As) is a widely distributed trace element which is known to be associated with numerous adverse effects on human beings and animals. Arsenic trioxide (As2O3) is an inorganic arsenical-containing toxic compound. The effect of excessive amounts of As2O3 exposure on gastrointestinal tract tissue damage in cocks is still unknown. This study was conducted to investigate the effect of As2O3 exposure on gastrointestinal tract tissue damage in cocks. In total, 72 1-day-old male Hyline cocks were randomly divided into four groups and fed either a commercial diet or an As2O3 supplement diet containing 7.5, 15, and 30 mg/kg As2O3. The experiment lasted for 90 days and gastrointestinal tract tissue samples (gizzard, glandular stomach, duodenum, jejunum, ileum, cecum, and rectum) were collected at 30, 60, and 90 days. Catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) activities; malondialdehyde (MDA) contents; and hydroxyl radical (OH·)-mediated inhibition were examined. Furthermore, the results demonstrated that MDA content in the gastrointestinal tract was increased, while the activities of CAT, GSH, and GSH-Px and the ability to resist OH· was decreased in the As2O3 treatment groups. Extensive damage was observed in the gastrointestinal tract. These findings indicated that As2O3 exposure caused oxidative damage in the gastrointestinal tract of cocks due to alterations in antioxidant enzyme activities and elevation of free radicals.

  3. Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

    Institute of Scientific and Technical Information of China (English)

    LI Shu Gang; GUO Shu Xia; DING Yu Song; NIU Qiang; XU Shang Zhi; PANG Li Juan; MA Ru Lin; JING Ming Xia; FENG Gang Ling; LIU Jia Ming

    2015-01-01

    Objective To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg);ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO+GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

  4. [Arsenic - Poison or medicine?].

    Science.gov (United States)

    Kulik-Kupka, Karolina; Koszowska, Aneta; Brończyk-Puzoń, Anna; Nowak, Justyna; Gwizdek, Katarzyna; Zubelewicz-Szkodzińska, Barbara

    2016-01-01

    Arsenic (As) is commonly known as a poison. Only a few people know that As has also been widely used in medicine. In the past years As and its compounds were used as a medicine for the treatment of such diseases as diabetes, psoriasis, syphilis, skin ulcers and joint diseases. Nowadays As is also used especially in the treatment of patients with acute promyelocytic leukemia. The International Agency for Research on Cancer (IARC) has recognized arsenic as an element with carcinogenic effect evidenced by epidemiological studies, but as previously mentioned it is also used in the treatment of neoplastic diseases. This underlines the specificity of the arsenic effects. Arsenic occurs widely in the natural environment, for example, it is present in soil and water, which contributes to its migration to food products. Long exposure to this element may lead to liver damages and also to changes in myocardium. Bearing in mind that such serious health problems can occur, monitoring of the As presence in the environmental media plays a very important role. In addition, the occupational risk of As exposure in the workplace should be identified and checked. Also the standards for As presence in food should be established. This paper presents a review of the 2015 publications based on the Medical database like PubMed and Polish Medical Bibliography. It includes the most important information about arsenic in both forms, poison and medicine.

  5. Chronic arsenic poisoning.

    Science.gov (United States)

    Hall, Alan H

    2002-03-10

    Symptomatic arsenic poisoning is not often seen in occupational exposure settings. Attempted homicide and deliberate long-term poisoning have resulted in chronic toxicity. Skin pigmentation changes, palmar and plantar hyperkeratoses, gastrointestinal symptoms, anemia, and liver disease are common. Noncirrhotic portal hypertension with bleeding esophageal varices, splenomegaly, and hypersplenism may occur. A metallic taste, gastrointestinal disturbances, and Mee's lines may be seen. Bone marrow depression is common. 'Blackfoot disease' has been associated with arsenic-contaminated drinking water in Taiwan; Raynaud's phenomenon and acrocyanosis also may occur. Large numbers of persons in areas of India, Pakistan, and several other countries have been chronically poisoned from naturally occurring arsenic in ground water. Toxic delirium and encephalopathy can be present. CCA-treated wood (chromated copper arsenate) is not a health risk unless burned in fireplaces or woodstoves. Peripheral neuropathy may also occur. Workplace exposure or chronic ingestion of arsenic-contaminated water or arsenical medications is associated with development of skin, lung, and other cancers. Treatment may incklude the use of chelating agents such as dimercaprol (BAL), dimercaptosuccinic acid (DMSA), and dimercaptopanesulfonic acid (DMPS).

  6. Silica ecosystem for synergistic biotransformation

    OpenAIRE

    Mutlu, Baris R.; Sakkos, Jonathan K.; Sujin Yeom; Wackett, Lawrence P.; Alptekin Aksan

    2016-01-01

    Synergistical bacterial species can perform more varied and complex transformations of chemical substances than either species alone, but this is rarely used commercially because of technical difficulties in maintaining mixed cultures. Typical problems with mixed cultures on scale are unrestrained growth of one bacterium, which leads to suboptimal population ratios, and lack of control over bacterial spatial distribution, which leads to inefficient substrate transport. To address these issues...

  7. Protective effect of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic toxicity in rats induced by inorganic arsenic.

    Science.gov (United States)

    Jiang, Yanhua; Wang, Lianzhu; Yao, Lin; Liu, Zhantao; Gao, Hua

    2013-09-01

    Arsenic, a potent environmental toxic agent, causes various hazardous effects on human health. This study was performed to evaluate the protective effects of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic stress of rats induced by arsenic trioxide (As2O3). The co-treatment of marine algae could slightly increase the growth rates of body weights compared to the As2O3-treated group. The marine algae application restored liver and renal function by preventing the increment in the activities of alanine transaminase and alkaline phosphatase, and the levels of total protein, blood urea nitrogen, and creatinine. The increase in the contents of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and decrease in the contents of high density lipoprotein cholesterol were observed in algae co-treated groups which indicated that marine algae could reverse the abnormal lipid metabolisms induced by arsenic. Moreover, these algae could protect the rats from lipid peroxidation by restoring the depletion of superoxide dismutase and glutathione peroxidase activities and sulfhydryl group contents, and lowering the enhanced malondialdehyde contents. Therefore, evidences indicate that L. japonica and P. haitanensis can serve as an effective regimen for treating arsenic poisoning.

  8. Protective effect of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic toxicity in rats induced by inorganic arsenic.

    Science.gov (United States)

    Jiang, Yanhua; Wang, Lianzhu; Yao, Lin; Liu, Zhantao; Gao, Hua

    2013-09-01

    Arsenic, a potent environmental toxic agent, causes various hazardous effects on human health. This study was performed to evaluate the protective effects of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic stress of rats induced by arsenic trioxide (As2O3). The co-treatment of marine algae could slightly increase the growth rates of body weights compared to the As2O3-treated group. The marine algae application restored liver and renal function by preventing the increment in the activities of alanine transaminase and alkaline phosphatase, and the levels of total protein, blood urea nitrogen, and creatinine. The increase in the contents of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and decrease in the contents of high density lipoprotein cholesterol were observed in algae co-treated groups which indicated that marine algae could reverse the abnormal lipid metabolisms induced by arsenic. Moreover, these algae could protect the rats from lipid peroxidation by restoring the depletion of superoxide dismutase and glutathione peroxidase activities and sulfhydryl group contents, and lowering the enhanced malondialdehyde contents. Therefore, evidences indicate that L. japonica and P. haitanensis can serve as an effective regimen for treating arsenic poisoning. PMID:23842700

  9. Inorganic arsenic toxicosis in cattle.

    Science.gov (United States)

    Riviere, J E; Boosinger, T R; Everson, R J

    1981-03-01

    In 4 occurrences of arsenic poisoning in cattle, the principal clinical sign was acute hemorrhagic diarrhea attributable to hemorrhagic gastroenteritis. Arsenic concentrations in the liver, kidney and rumen contents varied. In one occurrence, arsenic in the hair of affected survivors was assayed at 0.8-3.40 ppm, vs 0.09-0.10 ppm in randomly selected control samples of hair. Sudden death was the only clinical sign in another occurrence in which gastric contents contained arsenic at 671 ppm. In another occurrence, arsenic poisoning caused lesions similar to those of salmonellosis.

  10. Arsenic poisoning in cattle

    Energy Technology Data Exchange (ETDEWEB)

    McLennan, M.W.; Dodson, M.E.

    1972-06-01

    A case of acute arsenic poisoning in cattle was reported. The losses occurred on a property in the south east of South Australia. The weather had been hot for two or three days before the death occurred. The tank supplying the water trough had almost run dry. The cattle then attempted to meet their water requirements by drinking from the sheep dipping vat. A sample of rumen contents and a sample of water from the dipping vat were checked for arsenic. The rumen sample contained 45 ppM As/sub 2/O/sub 3/ and the sample of dipping fluid contained 200 ppM As. The lesions observed were similar to earlier reported arsenic poisoning. 5 references.

  11. Environmental Source of Arsenic Exposure

    Science.gov (United States)

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-01-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made. PMID:25284196

  12. Environmental source of arsenic exposure.

    Science.gov (United States)

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-09-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.

  13. ARSENIC SPECIATION ANALYSIS IN HUMAN SALIVA

    Science.gov (United States)

    Background: Determination of arsenic species in human saliva is potentially useful for biomonitoring of human exposure to arsenic and for studying arsenic metabolism. However, there is no report on the speciation analysis of arsenic in saliva. Methods: Arsenic species in saliva ...

  14. Synergistic effect of radon and sodium arsenite on DNA damage in HBE cells.

    Science.gov (United States)

    Liu, Xing; Sun, Bin; Wang, Xiaojuan; Nie, Jihua; Chen, Zhihai; An, Yan; Tong, Jian

    2016-01-01

    Human epidemiological studies showed that radon and arsenic exposures are major risk factors for lung cancer in Yunnan tin miners. However, biological evidence for this phenomenon is absent. In this study, HBE cells were exposed to different concentrations of sodium arsenite, different radon exposure times, or a combination of these two factors. The results showed a synergistic effect of radon and sodium arsenite in cell cytotoxicity as determined by cell viability. Elevated intracellular ROS levels and increased DNA damage indexed by comet assay and γ-H2AX were detected. Moreover, DNA HR repair in terms of Rad51 declined when the cells were exposed to both radon and sodium arsenite. The synergistic effect of radon and sodium arsenite in HBE cells may be attributed to the enhanced DSBs and inhibited HR pathway upon co-exposure.

  15. Exposure to inorganic arsenic can lead to gut microbe perturbations and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Jonathan Choiniere

    2016-09-01

    Full Text Available Arsenic is a carcinogenic environmental factor found in food and drinking water around the world. The mechanisms in which arsenic alters homeostasis are not fully understood. Over the past few decades, light has been shed on varying mechanisms in which arsenic induces cancer. Such mechanisms include gut microbe perturbations, genotoxic effects, and epigenetic modification. Gut microbe perturbations have been shown to increase the level of pathogen-associated molecular patterns such as lipopolysaccharide (LPS leading to uncontained inflammation. Increase in inflammation is the major factor in cirrhosis leading to hepatocellular carcinoma. Alterations in gut permeability and metabolites have also been observed as a fallout of arsenic induced gut microbe modification. The guts proximity and interaction through portal flow make the liver susceptible to gut perturbations and ensuing inflammatory responses. Genotoxic and epigenetic dysregulation induced by arsenic and its toxic metabolites present a more direct mechanism that works synergistically with gut microbe perturbations to induce the incidence of cancers. These pathways combined could be some of the main causes of arsenic-induced carcinogenesis.

  16. 含砷污酸资源化回收铜和砷的新工艺%Novel technique for recovery of copper and arsenic from arsenic-containing waste acid

    Institute of Scientific and Technical Information of China (English)

    郑雅杰; 张胜华; 龚昶

    2013-01-01

    以含砷污酸为原料,通过中和除杂-沉砷-洗涤-浸出-蒸发结晶-溶解制取三氧化二砷,实现含砷污酸的资源化。结果表明:将污酸中和至pH为2,使污酸的酸度降低;在中和液中加入硫酸铜,控制Cu和As的摩尔比为1.5:1,调节体系pH为8沉淀As,得到亚砷酸铜,As的沉淀率达到97.81%;通过洗涤除杂提高亚砷酸铜中As和Cu的含量;采用10%硫酸溶液,在液固比为5:1条件下浸出亚砷酸铜,所得溶液蒸发结晶得到三氧化二砷与硫酸铜的混合物;用水溶解该混合物后过滤得到硫酸铜溶液及符合 YS/T-99-1997As2O3-3号产品标准的三氧化二砷。%A novel technique for recovery of copper and arsenic from arsenic-containing waste acid discharged from copper smelter was proposed, and the process was composed of neutralization and purification-precipitation of arsenic-washing-leaching-evaporative crystallization-dissolution. Arsenic trioxide and cupric sulfate were obtained and resource of waste acid was accomplished. The results show that the acidity of the waste acid decreases and a certain amount of impurities is removed when the pH value of the system is neutralized to 2 by lime milk. Copper arsenite precipitates with arsenic precipitation efficiency of 97.81%when cupric sulfate is added into the neutralized solution. At the same time, the molar ratio of Cu and As is controlled at 1.5:1 and pH value of system is adjusted to 8 by sodium hydroxide. The contents of copper and arsenic in the precipitate of copper arsenite are increased by washing. 10%sulfuric acid was adopted to treat copper arsenite by leaching at liquid-solid ratio of 5:1, and then, a mixture of arsenic trioxide and cupric sulfate is obtained after the leachate is evaporated and crystallized. Finally, through dissolution and filtration of the solid mixture, cupric sulfate remains in the residual solution while arsenic trioxide meeting the product standard of YS/T-99

  17. Dynamic effects of autophagy on arsenic trioxide-induced death of human leukemia cell line HL60 cells

    Institute of Scientific and Technical Information of China (English)

    Ya-ping YANG; Zhong-qin LIANG; Bo GAO; Yan-li JIA; Zheng-hong QIN

    2008-01-01

    Aim: To evaluate the contribution of an autophagic mechanism to the As2O3-induced death of human acute myeloid leukaemia cell line HL60 cells. Methods: The growth inhibition of HL60 cells induced by As2O3 was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazohum bromide colorimetric assay. The ac-tivation of autophagy was determined with monodansylcadaverine labeling and transmission electron microscope. The role of autophagy in the As2O3-induced death of HL60 cells was assessed using autophagic and lysosomal inhibitors. Immunofluorescence, flow cytometry, and Western blot analysis were used to study the apoptotic and autophagic mechanisms. Results: After treatment with As2O3, the proliferation of HL60 cells was significantly inhibited and the formation of autophagosomes increased. The blockade of autophagy maturation with the autophagy-specific inhibitor 3-methyladenine (3-MA) or the lysosome-neutraliz-ing agent NH4C11 h before As2O3 potentiated the As2O3-induced death of HL60 cells. In contrast, 3-MA attenuated As2O3-induced death when administered 30 min after As2O3. 3-MA and NH4Cl also inhibited As2O3-induced upregulation of microtubule-associated protein 1 light chain 3, the protein required for autophagy in mammalian cells. Following As2O3, lysosomes were activated as indicated by increased levels of cathepsins B and L. The apoptotic response of HL60 cells to As2O3 was suggested by the collapse of mitochondrial membrane potential, re-lease of cytochrome c from mitochondria, and the activation of caspase-3. Pre-treatment with 3-MA prior to As2O3 amplified these apoptotic signals, while post-treatment with 3-MA 30 min after As2O3 attenuated the apoptotic pathways. Conclusion: Autophagy plays complex roles in the As2O3-induced death of HL60 cells; it inhibits As2O3-induced apoptosis in the initiation stage, but amplifies the AS2O3-mediated apoptotic program if it is persistently activated.

  18. A Meta-Analysis of Arsenic Trioxide Combined with Transcatheter Arterial Chemoembolization for Treatment of Primary Hepatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Ling He

    2016-01-01

    Full Text Available Primary hepatic carcinoma (PHC is one of the most common malignant tumours in the world. More and more research has shown that As2O3 combined with TACE has a good curative effect in treating PHC. The objectives of this study were to evaluate the therapeutic efficacy and safety of As2O3 combined with TACE in treating PHC. The CNKI, VIP, Wanfang, PubMed, and Cochrane databases were searched from their inception until December 2015. Randomized controlled trials (RCTs comparing As2O3 combined with TACE versus TACE alone in treating PHC were identified. Stata SE 12.0 was used for data analysis. 17 RCTs with 1055 patients were included. Meta-analysis showed that, compared with TACE alone, As2O3 combined with TACE showed significant effects in improving the clinical efficacy rate (P<0.01, decreasing the value of alpha-fetoprotein (P<0.01, increasing the one-year survival rate (P<0.01, and improving the quality of life of PHC patients (P<0.01. Fifteen studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, As2O3 combined with TACE therapy appears to be potentially effective in treating PHC and is generally safe. However, further studies with rigorous designs trials and multiregional cooperation trials are needed.

  19. Comparison of radiation shielding ratios of nano-sized bismuth trioxide and molybdenum

    Science.gov (United States)

    Cho, J. H.; Kim, M. S.; Rhim, J. D.

    2015-07-01

    In this study, radiation shielding fibers using non-hazardous nano-sized bismuth trioxide and molybdenum instead of lead were developed and evaluated. Among the elements with high densities and atomic numbers, non-hazardous elements such as bismuth trioxide and molybdenum were chosen as a shielding element. Then, bismuth trioxide (Bi2O3) with average particle size 1-500 µm was ball milled for 10 min to produce a powdered form of nanoparticles with average particle size of 10-100 nm. Bismuth trioxide nanoparticles were dispersed to make a colloidal suspension, followed by spreading and hardening onto one or two sides of fabric, to create the radiation shielding fabric. The thicknesses of the shielding sheets using nano-sized bismuth and molybdenum were 0.4 and 0.7 mm. According to the lead equivalent test of X-ray shielding products suggested by KS, the equivalent dose was measured, followed by calculation of the shielding rate. The shielding rate of bismuth with 0.4 mm thickness and at 50 kVp was 90.5%, which is comparable to lead of 0.082 mm thickness. The shielding rate of molybdenum was 51.89%%, which is comparable to lead of 0.034 mm. At a thickness of 0.7 mm, the shielding rate of bismuth was 98.73%, equivalent to 0.101 mm Pb, whereas the shielding rate of molybdenum was 74.68%, equivalent to 0.045 mm Pb. In conclusion, the radiation shielding fibers using nano-sized bismuth developed in this study are capable of reducing radiation exposure by X-ray and its low-dose scatter ray.

  20. Optical characteristics of aerosol trioxide dialuminum at the IR wavelength range

    Science.gov (United States)

    Voitsekhovskaya, O. K.; Shefer, O. V.; Kashirskii, D. E.

    2015-11-01

    In this work, a numerical study of the transmission function, extinction coefficient, scattering coefficient, and absorption coefficient of the aerosol generated by the jet engine emissions was performed. Analyzing the calculation results of the IR optical characteristics of anthropogenic emissions containing the dialuminum trioxide was carried out. The spectral features of the optical characteristics of the medium caused by the average size, concentration and complex refractive index of the particles were illustrated.

  1. Success Rate of Formocresol Pulpotomy versus Mineral Trioxide Aggregate in Human Primary Molar Tooth

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    S E Jabbarifar

    2004-12-01

    Full Text Available Background: In spite of long time and broad use of formaldehyde derivates (Fixation agent in primary tooth pulp treatment, There is some concerns about these derivates such as variability, inconsistency success rate, mutagenicity, cytotoxicity, alergenicity, and some other potential health hazards of them. Therefore other alternative pulpotomy procedures like Bioactive glass (BAG, Glutaraldehyde (2%, Hydroxyappetite (HA, Bone dried freezed (BDF, ferric sulfate (15%, laser, Electrosurgery (ES, Bone Morphogenic proteins (BMP, recombinant protein-1 (RP1, and Mineral Trioxide Aggregate (MTA have been compared. The purpose of this clinical trial is to assess radiographic and clinical success rate of Formocresol (FC pulpotomy in compare with MTA in human primary molar teeth. Methods: 64 molars were pulpotomized equally and randomly with mineral trioxide Aggregate and Formocresol. Prior to trial, we defined a case as failure, when one or more of the events such as external root resorption, internal root resorption, periapical and furca lucency, pain, swelling, mobility, dental abscess, or early extraction appeared. Every treated tooth was defined as successful, if any noted evident was not shown. Results: Totally, 60 teeth treatment (92.2 percent were successful and 7.8 percent were failed. Failure and success rates for MTA group were 6.3 and 93.7 percent, respectively. Failure and success rates in FC group were 8.4 and 90.2 percent respectively. The difference between MTA and FC treatment methods was not significant (Fisher Exact test. Conclusion: Findings of this study show that mineral trioxide aggregate can be an alternative procedure for FC pulpotomy of primary tooth. Keywords: Mineral trioxide aggregate, formocresol, pulpotomy, success and failure rate.

  2. Dissolution kinetics and thermodynamic analysis of vanadium trioxide during pressure oxidation

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    The dissolution kinetics of vanadium trioxide in sulphuric acid-oxygen medium was examined. It was determined that the concentration of sulphuric acid and stirring speed above 800 r min 1 did not significantly affect vanadium extraction. The dissolution rate increased with increasing temperature and oxygen partial pressure, but decreased with increasing particle size. The dissolution kinetics was controlled by the chemical reaction at the surface with the estimated activation energy of 43.46 kJ·mol-1. The l...

  3. Arsenic and cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Bianchi F.

    2013-04-01

    Full Text Available A growing body of epidemiologic, experimental and clinical evidence shows that arsenic may exert relevant cardiovascular effects with early damage such as endothelial dysfunction. Early biomarkers of cardiovascular damage together with markers of exposure, genetic and epigenetic effects, DNA damage, apoptosis, oxidative stress remain unexplored and a study is ongoing in Italy.

  4. Electrosprayed molybdenum trioxide aqueous solution and its application in organic photovoltaic cells.

    Science.gov (United States)

    Suzuki, Katsumi; Fukuda, Takeshi; Liao, Yingjie

    2014-01-01

    A molybdenum trioxide thin film with smooth surface and uniform thickness was successfully achieved by an electrospray deposition method using an aqueous solution with a drastically low concentration of 0.05 wt%. Previous papers demonstrated that an additive solvent technique is useful for depositing the thin film by the electrospray deposition, and the high vapor pressure and a low surface tension of an additive solvent were found to be important factors. As a result, the smooth molybdenum trioxide thin film was obtained when the acetonitrile was used as the additive solvent. Furthermore, the vapor pressure of acetone is much higher than that of aqueous solution, and this indicates that the acetone is easily evaporated after spraying from the glass capillary. By optimizing a concentration of acetone in the molybdenum aqueous solution, a minimum root mean square roughness of the MoO3 thin film became 3.7 nm. In addition, an organic photovoltaic cell was also demonstrated using the molybdenum trioxide as a hole transport layer. Highest photoconversion efficiency was 1.72%, a value comparable to that using conventional thermal evaporation process even though the aqueous solution was used for the solution process. The photovonversion efficiency was not an optimized value, and the higher value can be achieved by optimizing the coating condition of the active layer.

  5. Electrosprayed molybdenum trioxide aqueous solution and its application in organic photovoltaic cells.

    Directory of Open Access Journals (Sweden)

    Katsumi Suzuki

    Full Text Available A molybdenum trioxide thin film with smooth surface and uniform thickness was successfully achieved by an electrospray deposition method using an aqueous solution with a drastically low concentration of 0.05 wt%. Previous papers demonstrated that an additive solvent technique is useful for depositing the thin film by the electrospray deposition, and the high vapor pressure and a low surface tension of an additive solvent were found to be important factors. As a result, the smooth molybdenum trioxide thin film was obtained when the acetonitrile was used as the additive solvent. Furthermore, the vapor pressure of acetone is much higher than that of aqueous solution, and this indicates that the acetone is easily evaporated after spraying from the glass capillary. By optimizing a concentration of acetone in the molybdenum aqueous solution, a minimum root mean square roughness of the MoO3 thin film became 3.7 nm. In addition, an organic photovoltaic cell was also demonstrated using the molybdenum trioxide as a hole transport layer. Highest photoconversion efficiency was 1.72%, a value comparable to that using conventional thermal evaporation process even though the aqueous solution was used for the solution process. The photovonversion efficiency was not an optimized value, and the higher value can be achieved by optimizing the coating condition of the active layer.

  6. Plutonium and transplutonium element trioxides: molecular structures, chemical bonding, and isomers.

    Science.gov (United States)

    Zaitsevskii, Andréi

    2015-10-14

    Ground-state equilibrium geometries, energetics, and vibrational frequencies of AnO3 molecules, An = Pu through Cf, and their isomers are calculated using an accurate small-core pseudopotential model and the two-component relativistic density functional theory. The qualitative features of chemical bonding in these molecules are discussed in terms of oxidation states and bond orders. The actinide oxidation state (VI) is reached only in the plutonium trioxide molecule, whereas heavier actinide atoms in T-shaped trioxide molecules should be considered as pentavalent. At least at low temperatures, PuO3 and, to a lesser degree, AmO3 and BkO3 molecules should be stable both with respect to the isomerization into oxoperoxides or oxosuperoxides and the decay into dioxides and molecular oxygen. These trioxides can form dimers with significant (above 250 kJ mol(-1)) dissociation energies; the oxidation states of actinide atoms in the lowest-energy configurations of these dimers coincide with those in the corresponding monomers. The ability to reach high oxidation states in oxygen compounds gradually decreases from Pu onwards, with the only exception being the unexpectedly stable Bk(v)O3. PMID:26343514

  7. Synthesis and performance of bismuth trioxide nanoparticles for high energy gas generator use.

    Science.gov (United States)

    Martirosyan, K S; Wang, L; Vicent, A; Luss, D

    2009-10-01

    Our experiments showed that the combustion of an Al-Bi2O3 nanoparticle mixture generated the highest pressure pulse among common nanothermite reactions and can potentially be used as a nanoenergetic gas generator. The combustion front propagation velocity and rate of energy release increased by up to three orders of magnitude when the particle size was reduced to a nanosize range for both the aluminum and the oxidizer. We developed a novel one-step (metal nitrate-glycine) combustion synthesis of nanostructured amorphous-like and highly crystalline bismuth trioxide nanoparticles. The combustion synthesis was conducted using a solution of molten bismuth nitrate as an oxidizer and glycine as a fuel. The glycine was completely combusted during the thermal decomposition of the bismuth nitrate pentahydrate and generated a temperature front that propagated through the sample. Increasing the fuel concentration increased the maximum combustion temperature from 280 to 1200 degrees C and the Bi2O3 particle size from 20 to 100 nm. The oxidizer/fuel ratio had a strong impact on the bismuth trioxide particle crystallinity. At low temperature (280 degrees C), amorphous-like bismuth trioxide nanoparticles formed, while at T > or =370 degrees C the structures were crystalline. A peak pressure of approximately 12 MPa and a thermal front propagating velocity of approximately 2500 m s(-1) were achieved during the combustion of an Al-Bi2O3 mixture containing 80 wt% of the synthesized Bi2O3 crystalline nanoparticles (size: 40-50 nm).

  8. Rural methods to mitigate arsenic contaminated water

    OpenAIRE

    Parajuli, Krishna

    2013-01-01

    Consumption of arsenic contaminated water is one of the burning issues in the rural world. Poor public awareness program about health effects of drinking arsenic contaminated water and the rural methods to mitigate this problem poses a great threat of arsenic poisoning many people of the rural world. In this thesis, arsenic removal efficiency and the working mechanism of four rural and economical arsenic mitigation technologies i.e. solar oxidation and reduction of arsenic (SORAS), Bucket tr...

  9. Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study

    Science.gov (United States)

    Graziano, Joseph H; Parvez, Faruque; Liu, Mengling; Slavkovich, Vesna; Kalra, Tara; Argos, Maria; Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Levy, Diane; van Geen, Alexander

    2011-01-01

    Objective To evaluate the association between arsenic exposure and mortality from cardiovascular disease and to assess whether cigarette smoking influences the association. Design Prospective cohort study with arsenic exposure measured in drinking water from wells and urine. Setting General population in Araihazar, Bangladesh. Participants 11 746 men and women who provided urine samples in 2000 and were followed up for an average of 6.6 years. Main outcome measure Death from cardiovascular disease. Results 198 people died from diseases of circulatory system, accounting for 43% of total mortality in the population. The mortality rate for cardiovascular disease was 214.3 per 100 000 person years in people drinking water containing <12.0 µg/L arsenic, compared with 271.1 per 100 000 person years in people drinking water with ≥12.0 µg/L arsenic. There was a dose-response relation between exposure to arsenic in well water assessed at baseline and mortality from ischaemic heart disease and other heart disease; the hazard ratios in increasing quarters of arsenic concentration in well water (0.1-12.0, 12.1-62.0, 62.1-148.0, and 148.1-864.0 µg/L) were 1.00 (reference), 1.22 (0.65 to 2.32), 1.35 (0.71 to 2.57), and 1.92 (1.07 to 3.43) (P=0.0019 for trend), respectively, after adjustment for potential confounders including age, sex, smoking status, educational attainment, body mass index (BMI), and changes in urinary arsenic concentration since baseline. Similar associations were observed when baseline total urinary arsenic was used as the exposure variable and for mortality from ischaemic heart disease specifically. The data indicate a significant synergistic interaction between arsenic exposure and cigarette smoking in mortality from ischaemic heart disease and other heart disease. In particular, the hazard ratio for the joint effect of a moderate level of arsenic exposure (middle third of well arsenic concentration 25.3-114.0 µg/L, mean 63.5 µg/L) and

  10. Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China.

    OpenAIRE

    Liu, Jie; Zheng, Baoshan; Aposhian, H. Vasken; Zhou, Yunshu; Chen, Ming-liang; Zhang, Aihua; Waalkes, Michael P.

    2002-01-01

    Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here we report the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China. Coal in this region has undergone mineralization and thus produces high concentrations of arsenic. Coal is burned inside the home in open pits for daily cooki...

  11. Moonshine-related arsenic poisoning.

    Science.gov (United States)

    Gerhardt, R E; Crecelius, E A; Hudson, J B

    1980-02-01

    Twelve sequential cases of arsenic poisoning were reviewed for possible sources of ingestion. Contaminated illicit whiskey (moonshine) appeared to be the source in approximately 50% of the patients. An analysis of.confiscated moonshine revealed that occasional specimens contained high levels of arsenic as a contaminant. Although arsenic poisoning occurs relatively infrequently, contaminated moonshine may be an important cause of the poisoning in some areas of the country.

  12. 采用硫化砷渣制备三氧化二砷工艺%Preparation of arsenic trioxide from arsenic sulfide slag

    Institute of Scientific and Technical Information of China (English)

    郑雅杰; 刘万宇; 白猛; 张传福

    2008-01-01

    硫化砷渣经氢氧化钠溶液浸出、空气氧化脱硫和SO2还原制备得到As2O3.研究结果表明:当NaOH与As2S3物质的量比为7.2-1,固体质量与液体体积之比为1-6,反应温度为90 ℃,反应时间为2 h,转速为300 r/min时,用氢氧化钠溶液浸取硫化砷渣,其砷的浸取率达到95.90%;过滤后在碱浸液中通空气脱除碱浸液中Na3AsS3中的硫;当反应时间为10 h,反应温度为30 ℃,空气流量为120 L/h,对苯二酚和高锰酸钾质量浓度分别为1.5 g/L和0.5 g/L,木质素磺酸钠质量浓度为0.13 g/L时,脱硫率可达到96.00%;当pH值为0,反应时间为1 h,反应温度为30 ℃,砷质量浓度为60.00 g/L时通入SO2还原溶液中AsO43-,产物中As2O3含量和砷回收率分别达到92.14%和95.21%;稀硫酸洗涤后,As2O3纯度达95.14%.

  13. INFLUENCE OF MORINGA OLEIFERA (DRUM-STICK FRUIT EXTRACT ON HAEMATOLOGICAL PROFILE FOLLOWING REPEATED EXPOSURE TO LOW LEVELS OF ARSENIC THROUGH FEED ON RATS

    Directory of Open Access Journals (Sweden)

    Vaibhav R. Pachade

    2012-01-01

    Full Text Available Effect of Moringa oleifera fruits hot methanolic extract (MFE, if any, in minimizing the adverse reactions of repeated exposure to arsenic trioxide (AT in feed was investigated in Wistar rats with reference to haematological profile. Three groups of rats each containing 10 (5male+5female were used. The group I served as negative control. Rats of group II were fed arsenic trioxide (AT alone @ 100 ppm in feed while those of group III simultaneously received AT (@100 ppm and MFE (50 mg/kg/day for 28 days. Blood samples were collected from retroorbital plexus for estimation of hematological parameters (haemoglobin, PCV, TEC, MCH, MCHC, MCV of different groups on 0 day, 15th day and 29th day respectively. Exposure to AT through feed in group II resulted in significant (P<0.05 decrease in haemoglobin, TEC and MCHC, accompanied by increased MCV, with no significant alteration of PCV or MCH of the rats. While rats of group III treated with AT (@100 ppm and MFE (50 mg/kg/day also resulted in same consequences as it was in group II but it was slightly less than that of group II suggesting of mild non significant protective effect.

  14. Arsenic poisoning of Bangladesh groundwater

    Science.gov (United States)

    Nickson, Ross; McArthur, John; Burgess, William; Ahmed, Kazi Matin; Ravenscroft, Peter; Rahmanñ, Mizanur

    1998-09-01

    In Bangladesh and West Bengal, alluvial Ganges aquifers used for public water supply are polluted with naturally occurring arsenic, which adversely affects the health of millions of people. Here we show that the arsenic derives from the reductive dissolution of arsenic-rich iron oxyhydroxides, which in turn are derived from weathering of base-metal sulphides. This finding means it should now be possible, by sedimentological study of the Ganges alluvial sediments, to guide the placement of new water wells so they will be free of arsenic.

  15. Arsenic content of homeopathic medicines

    Energy Technology Data Exchange (ETDEWEB)

    Kerr, H.D.; Saryan, L.A.

    1986-01-01

    In order to test the widely held assumption that homeopathic medicines contain negligible quantities of their major ingredients, six such medicines labeled in Latin as containing arsenic were purchased over the counter and by mail order and their arsenic contents measured. Values determined were similar to those expected from label information in only two of six and were markedly at variance in the remaining four. Arsenic was present in notable quantities in two preparations. Most sales personnel interviewed could not identify arsenic as being an ingredient in these preparations and were therefore incapable of warning the general public of possible dangers from ingestion. No such warnings appeared on the labels.

  16. Electronic structure of trioxide, oxoperoxide, oxosuperoxide, and ozonide clusters of the 3d elements: density functional theory study.

    Science.gov (United States)

    Uzunova, Ellie L

    2011-03-01

    The trioxide clusters with stoichiometry MO3, and the structural isomers with side-on and end-on bonded oxygen atoms, are studied by DFT with the B1LYP functional. For the first half of the 3d elements row (Sc to Cr), pyramidal or distorted pyramidal structures dominate among the trioxide and oxoperoxide ground states, while the remaining elements form planar trioxides, oxoperoxides, oxosuperoxides, and ozonides. Low-lying trioxide clusters are formed by Ti, V, Cr, and Mn, among which the distorted pyramidal VO3 in the (2)A'' state, the pyramidal CrO3 in the (1)A1 state, and the planar MnO3 in the (2)A1' state are global minima. With the exception of the middle-row elements Mn, Fe, and Co, the magnetic moment of the ground-state clusters is formed with a major contribution from unpaired electrons located at the oxygen atoms. The stability of trioxides and oxoperoxides toward release of molecular oxygen is significantly higher for Sc, Ti, and V than for the remaining elements of the row. A trend of increasing the capability to dissociate one oxygen molecule is observed from Cr to Cu, with the exception of OFe(O2) being more reactive than OCo(O2). A gradual increase of reactivity from Ti to Cu is observed for the complete fragmentation reaction M + O + O2. PMID:21299242

  17. Homicidal arsenic poisoning.

    Science.gov (United States)

    Duncan, Andrew; Taylor, Andrew; Leese, Elizabeth; Allen, Sam; Morton, Jackie; McAdam, Julie

    2015-07-01

    The case of a 50-year-old man who died mysteriously after being admitted to hospital is reported. He had raised the possibility of being poisoned prior to his death. A Coroner's post-mortem did not reveal the cause of death but this was subsequently established by post-mortem trace element analysis of liver, urine, blood and hair all of which revealed very high arsenic concentrations.

  18. A Phytoremediation Strategy for Arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Meagher, Richard B.

    2005-06-01

    A Phytoremediation Strategy for Arsenic Progress Report May, 2005 Richard B. Meagher Principal Investigator Arsenic pollution affects the health of several hundred millions of people world wide, and an estimated 10 million Americans have unsafe levels of arsenic in their drinking water. However, few environmentally sound remedies for cleaning up arsenic contaminated soil and water have been proposed. Phytoremediation, the use of plants to extract and sequester environmental pollutants, is one new technology that offers an ecologically sound solution to a devastating problem. We propose that it is less disruptive to the environment to harvest and dispose of several thousand pounds per acre of contaminated aboveground plant material, than to excavate and dispose of 1 to 5 million pounds of contaminated soil per acre (assumes contamination runs 3 ft deep). Our objective is to develop a genetics-based phytoremediation strategy for arsenic removal that can be used in any plant species. This strategy requires the enhanced expression of several transgenes from diverse sources. Our working hypothesis is that organ-specific expression of several genes controlling the transport, electrochemical state, and binding of arsenic will result in the efficient extraction and hyperaccumulation of arsenic into aboveground plant tissues. This hypothesis is supported by theoretical arguments and strong preliminary data. We proposed six Specific Aims focused on testing and developing this arsenic phytoremediation strategy. During the first 18 months of the grant we made significant progress on five Specific Aims and began work on the sixth as summarized below. Specific Aim 1: Enhance plant arsenic resistance and greatly expand sinks for arsenite by expressing elevated levels of thiol-rich, arsenic-binding peptides. Hyperaccumulation of arsenic depends upon making plants that are both highly tolerant to arsenic and that have the capacity to store large amounts of arsenic aboveground

  19. Association between Chronic Arsenic Exposure and Nutritional Status among the Women of Child Bearing Age: A Case-Control Study in Bangladesh

    Directory of Open Access Journals (Sweden)

    Abul H. Milton

    2010-07-01

    Full Text Available The role of nutritional factors in arsenic metabolism and toxicity is yet to be fully elucidated. A low protein diet results in decreased excretion of DMA and increased tissue retention of arsenic in experimental studies. Malnourished women carry a higher risk of adverse pregnancy outcomes. Chronic exposure to high arsenic (>50 µg/L through drinking water also increases the risk of adverse pregnancy outcomes. The synergistic effects (if any of malnutrition and chronic arsenic exposure may worsen the adverse pregnancy outcomes. This population based case control study reports the association between chronic arsenic exposure and nutritional status among the rural women in Bangladesh. 348 cases (BMI < 18.5 and 360 controls (BMI 18.5–24.99 were recruited from a baseline survey conducted among 2,341 women. An excess risk for malnutrition was observed among the participants chronically exposed to higher concentrations of arsenic in drinking water after adjusting for potential confounders such as participant’s age, religion, education, monthly household income and history of oral contraceptive pills. Women exposed to arsenic >50 µg/L were at 1.9 times (Odds Ratio = 1.9, 95% CI = 1.1–3.6 increased risk of malnutrition compared to unexposed. The findings of this study suggest that chronic arsenic exposure is likely to contribute to poor nutritional status among women of 20–45 years.

  20. ARSENIC - SUSCEPTIBILITY & IN UTERO EFFECTS

    Science.gov (United States)

    Exposure to inorganic arsenic remains a serious public health problem at many locations worldwide. If has often been noted that prevalences of signs and symptoms of chronic arsenic poisoning differ among various populations. For example, skin lesions or peripheral vascular dis...

  1. Arsenic Mobility and Groundwater Extraction in Bangladesh

    Science.gov (United States)

    Harvey, Charles F.; Swartz, Christopher H.; Badruzzaman, A. B. M.; Keon-Blute, Nicole; Yu, Winston; Ali, M. Ashraf; Jay, Jenny; Beckie, Roger; Niedan, Volker; Brabander, Daniel; Oates, Peter M.; Ashfaque, Khandaker N.; Islam, Shafiqul; Hemond, Harold F.; Ahmed, M. Feroze

    2002-11-01

    High levels of arsenic in well water are causing widespread poisoning in Bangladesh. In a typical aquifer in southern Bangladesh, chemical data imply that arsenic mobilization is associated with recent inflow of carbon. High concentrations of radiocarbon-young methane indicate that young carbon has driven recent biogeochemical processes, and irrigation pumping is sufficient to have drawn water to the depth where dissolved arsenic is at a maximum. The results of field injection of molasses, nitrate, and low-arsenic water show that organic carbon or its degradation products may quickly mobilize arsenic, oxidants may lower arsenic concentrations, and sorption of arsenic is limited by saturation of aquifer materials.

  2. Arsenic toxicity to cladocerans isolated and associated with iron: implications for aquatic environments

    Directory of Open Access Journals (Sweden)

    SUELLEN C.M. SALES

    2016-01-01

    Full Text Available ABSTRACT Arsenic is an ametal ubiquitous in nature and known by its high toxicity. Many studies have tried to elucidate the arsenic metabolism in the cell and its impact to plants, animals and human health. In aqueous phase, inorganic arsenic is more common and its oxidation state (As III and As V depends on physical and chemical environmental conditions. The aim of this study was to evaluate toxicity of arsenic to Daphnia similis and Ceriodaphnia silvestrii, isolated and associated with iron. The results showed differences in toxicity of As III and As V to both species. Effective concentration (EC50 mean values were 0.45 mg L-1 (As III and 0.54 mg L-1 (As V for D. similis, and 0.44 mg L-1 (As III and 0.69 mg L-1 (As V for C. silvestrii. However, As V IC25 mean value was 0.59 mg L-1, indicating that C. silvestrii has mechanisms to reduce arsenic toxicity. On the other hand, when associated with iron at 0.02 and 2.00 mg L-1, EC50 values decreased for D. similis (0.34 and 0.38 mg L-1 as well as C. silvestrii (0.37 and 0.37 mg L-1, showing synergistic effect of these substances.

  3. In situ chemical fixation of arsenic-contaminated soils: Anexperimental study

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Li; Donahoe, Rona J.; Redwine, James C.

    2007-03-27

    This paper reports the results of an experimentalstudytesting a low-cost in situ chemical fixation method designed to reclaimarsenic-contaminated subsurface soils. Subsurface soils from severalindustrial sites in southeastern U.S. were contaminated with arsenicthrough heavy application of herbicide containing arsenic trioxide. Themean concentrations of environmentally available arsenic in soilscollected from the two study sites, FW and BH, are 325 mg/kg and 900mg/kg, respectively. The soils are sandy loams with varying mineralogicaland organic contents. The previous study [Yang L, Donahoe RJ. The form,distribution and mobility of arsenic in soils contaminated by arsenictrioxide, at sites in Southeast USA. Appl Geochem 2007;22:320 341]indicated that a large portion of the arsenic in both soils is associatedwith amorphous aluminum and iron oxyhydroxides and shows very slowrelease against leaching by synthetic precipitation. The soil's amorphousaluminum and iron oxyhydroxides content was found to have the mostsignificant effect on its ability to retain arsenic.Based on thisobservation, contaminated soils were reacted with different treatmentsolutions in an effort to promote the formation of insolublearsenic-bearing phases and thereby decrease the leachability of arsenic.Ferrous sulfate, potassium permanganate and calcium carbonate were usedas the reagents for the chemical fixation solutions evaluated in threesets of batch experiments: (1) FeSO4; (2) FeSO4 and KMnO4; (3) FeSO4,KMnO4 and CaCO3. The optimum treatment solutions for each soil wereidentified based on the mobility of arsenic during sequential leaching oftreated and untreated soils using the fluids described in EPA Method 1311[USEPA. Method 1311: toxicity characteristic leaching procedure. Testmethods for evaluating solid waste, physical/chemical methods. 3rd ed.Washington, DC: U.S. Environmental Protection Agency, Office of SolidWaste. U.S. Government Printing Office; 1992]toxic characteristicsleaching

  4. A systematic study of neutral and charged 3d-metal trioxides and tetraoxides

    Science.gov (United States)

    Pradhan, Kalpataru; Gutsev, Gennady L.; Weatherford, Charles A.; Jena, Purusottam

    2011-04-01

    Using density functional theory with generalized gradient approximation, we have performed a systematic study of the structure and properties of neutral and charged trioxides (MO3) and tetraoxides (MO4) of the 3d-metal atoms. The results of our calculations revealed a number of interesting features when moving along the 3d-metal series. (1) Geometrical configurations of the lowest total energy states of neutral and charged trioxides and tetraoxides are composed of oxo and/or peroxo groups, except for CuO3- and ZnO3- which possess a superoxo group, CuO4+ and ZnO4+ which possess two superoxo groups, and CuO3+, ZnO3+, and ZnO4- which possess an ozonide group. While peroxo groups are found in the early and late transition metals, all oxygen atoms bind chemically to the metal atom in the middle of the series. (2) Attachment or detachment of an electron to/from an oxide often leads to a change in the geometry. In some cases, two dissociatively attached oxygen atoms combine and form a peroxo group or a peroxo group transforms into a superoxo group and vice versa. (3) The adiabatic electron affinity of as many as two trioxides (VO3 and CoO3) and four tetraoxides (TiO4, CrO4, MnO4, and FeO4) are larger than the electron affinity of halogen atoms. All these oxides are hence superhalogens although only VO3 and MnO4 satisfy the general superhalogen formula.

  5. Arsenic concentrations in Chinese coals

    International Nuclear Information System (INIS)

    The arsenic concentrations in 297 coal samples were collected from the main coal-mines of 26 provinces in China were determined by molybdenum blue coloration method. These samples were collected from coals that vary widely in coal rank and coal-forming periods from the five main coal-bearing regions in China. Arsenic content in Chinese coals range between 0.24 to 71 mg/kg. The mean of the concentration of Arsenic is 6.4 ± 0.5 mg/kg and the geometric mean is 4.0 ± 8.5 mg/kg. The level of arsenic in China is higher in northeastern and southern provinces, but lower in northwestern provinces. The relationship between arsenic content and coal-forming period, coal rank is studied. It was observed that the arsenic contents decreases with coal rank in the order: Tertiary > Early Jurassic > Late Triassic > Late Jurassic > Middle Jurassic > Late Permian > Early Carboniferous > Middle Carboniferous > Late Carboniferous > Early Permian; It was also noted that the arsenic contents decrease in the order: Subbituminous > Anthracite > Bituminous. However, compared with the geological characteristics of coal forming region, coal rank and coal-forming period have little effect on the concentration of arsenic in Chinese coal. The average arsenic concentration of Chinese coal is lower than that of the whole world. The health problems in China derived from in coal (arsenism) are due largely to poor local life-style practices in cooking and home heating with coal rather than to high arsenic contents in the coal

  6. Monoblock Obturation Technique for Non-Vital Immature Permanent Maxillary Incisors Using Mineral Trioxide Aggregate: Results from Case Series

    International Nuclear Information System (INIS)

    Ten patients presented with non-vital immature teeth for root canal treatment. In all these cases the pre-operative clinical examination revealed apical periodontitis with a buccal sinus tract of endodontic origin. These cases were treated by a mineral trioxide aggregate (MTA) monoblock obturation technique. Follow-up evaluations were performed at 1 - 2 years after treatment. Eight out of 10 cases were associated with periradicular healing at follow-up evaluation. Mineral trioxide aggregate Monoblock obturation technique appears to be a valid material to obtain periradicular healing in teeth with open apices and necrotic pulps. (author)

  7. Resveratrol, a Natural Antioxidant, Has a Protective Effect on Liver Injury Induced by Inorganic Arsenic Exposure

    Directory of Open Access Journals (Sweden)

    Zhigang Zhang

    2014-01-01

    Full Text Available Resveratrol (Rev can ameliorate cytotoxic chemotherapy-induced toxicity and oxidative stress. Arsenic trioxide (As2O3 is a known cytotoxic environmental toxicant and a potent chemotherapeutic agent. However, the mechanisms by which resveratrol protects the liver against the cytotoxic effects of As2O3 are not known. Therefore, in the present study we investigated the mechanisms involved in the action of resveratrol using a cat model in which hepatotoxicity was induced by means of As2O3 treatment. We found that pretreatment with resveratrol, administered using a clinically comparable dose regimen, reversed changes in As2O3-induced morphological and liver parameters and resulted in a significant improvement in hepatic function. Resveratrol treatment also improved the activities of antioxidant enzymes and attenuated As2O3-induced increases in reactive oxygen species and malondialdehyde production. In addition, resveratrol attenuated the As2O3-induced reduction in the ratio of reduced glutathione to oxidized glutathione and the retention of arsenic in liver tissue. These findings provide a better understanding of the mechanisms whereby resveratrol modulates As2O3-induced changes in liver function and tissue morphology. They also provide a stronger rationale for the clinical utilization of resveratrol for the reduction of As2O3-induced hepatotoxicity.

  8. Obturating teeth with wide open apices using mineral trioxide aggregate: a case report.

    Science.gov (United States)

    Levenstein, H

    2002-07-01

    The conventional approach in handling a tooth with a wide open apex requiring endodontic treatment is by means of a procedure called apexification. The objective of treatment is to introduce calcium hydroxide mixed with sterile water or local anaesthetic into the root canal to create a hard-tissue-like formation or an apical plug to prevent extrusion of filling materials during obturation of teeth with wide open apices. This procedure may take anything from 6 months to 2 years. In 1999 a new material called mineral trioxide aggregate (MTA) was introduced to the dental profession for clinical use which has the ability to create an apical plug within a few weeks.

  9. Furcal-perforation repair with mineral trioxide aggregate: Two years follow-up

    Directory of Open Access Journals (Sweden)

    Emmanuel João Nogueira Leal da Silva

    2012-01-01

    Full Text Available Furcal perforations are significant iatrogenic complications of endodontic treatment and could lead to endodontic failure. Mineral trioxide aggregate (MTA has been regarded as an ideal material for perforation repair, retrograde filling, pulp capping, and apexification. This case report describes a furcal perforation in a maxillary first molar, which was repaired using MTA. The tooth was endodontically treated and coronally restored with resin composite. After 2 years, the absence of periradicular radiolucent lesions, pain, and swelling along with functional tooth stability indicated a successful outcome of sealing the perforation using MTA.

  10. Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells

    Institute of Scientific and Technical Information of China (English)

    Xiao Jing WANG; Jie YANG; Hui CANG; Yan Qiong ZOU; Jing YI

    2005-01-01

    Emodin (1,3,8-trihydroxy-6-methylanthraquinone) could enhance the sensitivity of tumor cells to arsenic trioxide (As2O3)-induced apoptosis via generation of ROS,but the molecular mechanism has not been elucidated.Here,we carried out cDNA microarray-based global transcription profiling of HeLa cells in response to As2O3/emodin cotreatment,comparing with As2O3-only treatment.The results showed that the expression of a number of genes was substantially altered at two time points.These genes are involved in different aspects of cell function.In addition to redox regulation and apoptosis,ROS affect genes encoding proteins associated with cell signaling,organelle functions,cell cycle,cytoskeleton,etc.These data suggest that based on the cytotoxicity of As2O3,emodin mobilize every genomic resource through which the As2O3-induced apoptosis is facilitated.

  11. Silica ecosystem for synergistic biotransformation

    Science.gov (United States)

    Mutlu, Baris R.; Sakkos, Jonathan K.; Yeom, Sujin; Wackett, Lawrence P.; Aksan, Alptekin

    2016-06-01

    Synergistical bacterial species can perform more varied and complex transformations of chemical substances than either species alone, but this is rarely used commercially because of technical difficulties in maintaining mixed cultures. Typical problems with mixed cultures on scale are unrestrained growth of one bacterium, which leads to suboptimal population ratios, and lack of control over bacterial spatial distribution, which leads to inefficient substrate transport. To address these issues, we designed and produced a synthetic ecosystem by co-encapsulation in a silica gel matrix, which enabled precise control of the microbial populations and their microenvironment. As a case study, two greatly different microorganisms: Pseudomonas sp. NCIB 9816 and Synechococcus elongatus PCC 7942 were encapsulated. NCIB 9816 can aerobically biotransform over 100 aromatic hydrocarbons, a feat useful for synthesis of higher value commodity chemicals or environmental remediation. In our system, NCIB 9816 was used for biotransformation of naphthalene (a model substrate) into CO2 and the cyanobacterium PCC 7942 was used to provide the necessary oxygen for the biotransformation reactions via photosynthesis. A mathematical model was constructed to determine the critical cell density parameter to maximize oxygen production, and was then used to maximize the biotransformation rate of the system.

  12. Effect of organic matter amendment, arsenic amendment and water management regime on rice grain arsenic species

    International Nuclear Information System (INIS)

    Arsenic accumulation in rice grain has been identified as a major problem in some regions of Asia. A study was conducted to investigate the effect of increased organic matter in the soil on the release of arsenic into soil pore water and accumulation of arsenic species within rice grain. It was observed that high concentrations of soil arsenic and organic matter caused a reduction in plant growth and delayed flowering time. Total grain arsenic accumulation was higher in the plants grown in high soil arsenic in combination with high organic matter, with an increase in the percentage of organic arsenic species observed. The results indicate that the application of organic matter should be done with caution in paddy soils which have high soil arsenic, as this may lead to an increase in accumulation of arsenic within rice grains. Results also confirm that flooding conditions substantially increase grain arsenic. -- Highlights: ► High soil arsenic and organic matter caused a reduction in plant growth. ► A delayed flowering time was observed in high arsenic and organic matter soil. ► Total grain arsenic increased in high arsenic and organic matter soil. ► Percentage organic arsenic in the grain altered in arsenic and organic matter soil. -- The addition of high amounts of organic matter to soils led to an increase in total rice grain arsenic, as well as alteration in the percentage arsenic species in the rice grains

  13. Flame-retardancy of a Cellulosic Fabric by the Application of Synergistic Effect between Ammonium Bromide and Antimony (Ⅲ)Oxide

    Institute of Scientific and Technical Information of China (English)

    MOSTASHARI Seyed Morteza; MOAFI Hadi Fallah

    2009-01-01

    The synergistic effect between ammonium bromide and antimony(Ⅲ) oxide as a nondurable finish on the flammability of 100% woven plain cotton fabric(with a density of 144 g/m2,the number of yarns 21 per 10 mm),has been investigated in this study. The laundered totally-dried, weighed specimens were impregnated with suitable concentration individual aqueous ammonium bromide and/or antimony (Ⅲ)oxide suspension solutions and some sets weIle impregnated with appropriate admixed solutions of the both chemicals.A vertical flame spread test Was then carried-out to characterize the flammability of the samples.An acceptable synergistic effect was then experi.enced by using an admixed bath containing 0.1 molar ammonium bromide and O.05 unit formal antimony trioxide solutions for impartation of flame.retardancy to a cotton fabric.The optimum mass of the mixture required to lm.Dart flame-retardancy was about 3.64 g of anhydrous additives per 100 g of fabric.The results obtained are in favor 0f Wall Effect Theory.Moreover synergistic eflfect indicating dehydration of the treated substrate by using this combination via thermogravimetry could be deduced.

  14. Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in rat bone-marrow after sub-chronic oral dosing.

    Science.gov (United States)

    Kirkland, David; Whitwell, James; Deyo, James; Serex, Tessa

    2007-03-01

    Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant synergist in a number of household products, as a fining agent in glass manufacture, and as a catalyst in the manufacture of various types of polyester plastics. It does not induce point mutations in bacteria or mammalian cells, but is able to induce chromosomal aberrations (CA) in cultured cells in vitro. Although no CA or micronuclei (MN) have been induced after acute oral dosing of mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one report, but did not result in increased MN in another. In order to further investigate its in vivo genotoxicity, Sb2O3 was dosed orally to groups of rats for 21 days at 250, 500 and 1000 mg/kg day. There were no clinical signs of toxicity in the Sb2O3-exposed animals except for some reductions in body-weight gain in the top dose group. Toxicokinetic measurements in a separate study confirmed bone-marrow exposure, and at higher levels than would have been achieved by single oral dosing. Large numbers of cells were scored for CA (600 metaphases/sex group) and MN (12,000 PCE/sex group) but frequencies of CA or MN in Sb2O3-treated rats were very similar to controls, and not biologically or statistically different, at all doses. These results provide further indication that Sb2O3 is not genotoxic to the bone marrow of rodents after 21 days of oral administration at high doses close to the maximum tolerated dose. PMID:17174592

  15. Osteoresorptive arsenic intoxication.

    Science.gov (United States)

    Dani, Sergio Ulhoa

    2013-04-01

    A 47-year-old woman consulted her dermatologist complaining whole body dermatitis, urticaria and irritating bullous eruptions on the plantar and side surfaces of her feet. She had had multiple hypopigmented spots on her skin since her early adulthood. The patient was treated with topical medication without significant improvement of symptoms. One year later she suffered a myocardial infarction, accompanied by refractory anaemia. At the age of 49, a breast cancer was diagnosed and shortly thereafter her last menstruation occurred. At age 50years, upon complaint of weight loss despite normal food intake, Hashimoto thyroiditis with latent hyperthyroidism, vitamin D insufficiency with secondary hyperparathyroidism, and poikilocytic anaemia with anisochromia, hypochromia, anisocytosis, elliptocytes, drepanocytes, dacryocytes, acanthocytes, echinocytes, schizocytes, stomatocytes and target cells were diagnosed. The osteodensitometric and laboratory examinations revealed osteoporosis with sustained elevation of urinary Dipyridinolin-crosslinks (u-Dpd), and urinary arsenic (u-As) of 500μg/l (equivalent to 0.5 parts per million-ppm, 2.5μg/mg creatinine/dl, u-As: Phosphate of 26μg/mmol; the estimated bone As:P and As/kg body weight were 500μg/g and 11.3mg/kg, respectively). Thalassemia, immunoglobinopathy and iron deficiency were excluded. Supplementation with oral vitamin D and calcium, and antiresorptive therapy with intravenous zolendronate normalised the u-Dpd, significantly decreased the urinary arsenic concentration, and cured the anemia and the urticaria. A diagnosis of osteoresorptive arsenic intoxication (ORAI) was established. PMID:23337042

  16. Statistical metamodeling for revealing synergistic antimicrobial interactions.

    Science.gov (United States)

    Chen, Hsiang Chia; Chen, Chia Hsiang; Gau, Vincent; Zhang, Donna D; Liao, Joseph C; Wang, Fei-Yue; Wong, Pak Kin

    2010-01-01

    Many bacterial pathogens are becoming drug resistant faster than we can develop new antimicrobials. To address this threat in public health, a metamodel antimicrobial cocktail optimization (MACO) scheme is demonstrated for rapid screening of potent antibiotic cocktails using uropathogenic clinical isolates as model systems. With the MACO scheme, only 18 parallel trials were required to determine a potent antimicrobial cocktail out of hundreds of possible combinations. In particular, trimethoprim and gentamicin were identified to work synergistically for inhibiting the bacterial growth. Sensitivity analysis indicated gentamicin functions as a synergist for trimethoprim, and reduces its minimum inhibitory concentration for 40-fold. Validation study also confirmed that the trimethoprim-gentamicin synergistic cocktail effectively inhibited the growths of multiple strains of uropathogenic clinical isolates. With its effectiveness and simplicity, the MACO scheme possesses the potential to serve as a generic platform for identifying synergistic antimicrobial cocktails toward management of bacterial infection in the future. PMID:21124958

  17. Statistical metamodeling for revealing synergistic antimicrobial interactions.

    Directory of Open Access Journals (Sweden)

    Hsiang Chia Chen

    Full Text Available Many bacterial pathogens are becoming drug resistant faster than we can develop new antimicrobials. To address this threat in public health, a metamodel antimicrobial cocktail optimization (MACO scheme is demonstrated for rapid screening of potent antibiotic cocktails using uropathogenic clinical isolates as model systems. With the MACO scheme, only 18 parallel trials were required to determine a potent antimicrobial cocktail out of hundreds of possible combinations. In particular, trimethoprim and gentamicin were identified to work synergistically for inhibiting the bacterial growth. Sensitivity analysis indicated gentamicin functions as a synergist for trimethoprim, and reduces its minimum inhibitory concentration for 40-fold. Validation study also confirmed that the trimethoprim-gentamicin synergistic cocktail effectively inhibited the growths of multiple strains of uropathogenic clinical isolates. With its effectiveness and simplicity, the MACO scheme possesses the potential to serve as a generic platform for identifying synergistic antimicrobial cocktails toward management of bacterial infection in the future.

  18. SYNERGISTIC WOOD PRESERVATIVES FOR REPLACEMENT OF CCA

    Science.gov (United States)

    The objective of this project was to evaluate the potential synergistic combinations of environmentally-safe biocides as wood preservatives. These wood preservatives could be potential replacements for the heavy-metal based CCA.Didecyldimethylammonium chloride [DDAC] was...

  19. Microbial responses to environmental arsenic.

    Science.gov (United States)

    Páez-Espino, David; Tamames, Javier; de Lorenzo, Víctor; Cánovas, David

    2009-02-01

    Microorganisms have evolved dynamic mechanisms for facing the toxicity of arsenic in the environment. In this sense, arsenic speciation and mobility is also affected by the microbial metabolism that participates in the biogeochemical cycle of the element. The ars operon constitutes the most ubiquitous and important scheme of arsenic tolerance in bacteria. This system mediates the extrusion of arsenite out of the cells. There are also other microbial activities that alter the chemical characteristics of arsenic: some strains are able to oxidize arsenite or reduce arsenate as part of their respiratory processes. These type of microorganisms require membrane associated proteins that transfer electrons from or to arsenic (AoxAB and ArrAB, respectively). Other enzymatic transformations, such as methylation-demethylation reactions, exchange inorganic arsenic into organic forms contributing to its complex environmental turnover. This short review highlights recent studies in ecology, biochemistry and molecular biology of these processes in bacteria, and also provides some examples of genetic engineering for enhanced arsenic accumulation based on phytochelatins or metallothionein-like proteins.

  20. Removing arsenic from drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Hathaway, S.W.; Rubel, R. (Environmental Protection Agency, Cincinnati, OH (USA))

    1987-08-01

    Pilot-plant tests of two treatment methods, activated alumina and ion exchange, for removing arsenic from drinking water were evaluated at the Fallon, Nevada, Naval Air Station (NAS). The arsenic concentration was 0.080-0.116 mg/liter, exceeding the 0.05 mg/liter maximum contaminant level. Although the valence of arsenic was not determined, in prechlorination process and test results suggest it was probably arsenic V. Chlorinated drinking water from the NAS was used for evaluating the efficacy of treatment under several different conditions. The activated alumina and ion exchange systems were operated through three different loading and regeneration cycles each. The major water quality factors affecting the removal of arsenic by these methods were pH of feedwater, arsenic concentration, sulfate concentration, and alkalinity. The major operational factors affecting removal were flow rate, down time, and media clogging. Capital and operating costs for arsenic removal are estimated for the activated alumina method at optimum pH (5.5) for each of the three small community systems drawing water from the same aquifer. In addition, several containers of the regeneration waste were used for a special study to characterize, dewater, and render the waste non-toxic for disposal in a sanitary landfill.

  1. The nature of chemical bond in trioxide Mi-UO3

    Directory of Open Access Journals (Sweden)

    Teterin Yury A.

    2002-01-01

    Full Text Available Low-energy X-ray photoelectron and conversion electron spectra from uranium trioxide were measured, and calculations were done for the [UO2O4]-6 (D4b cluster which reflects the structure of uranium close environment in MI-UO3 in the non-relativistic and relativistic Xa-DVM approximation. This enabled a satisfactory qualitative and in some cases quantitative agreement between the experimental and theoretical data, and interpretation of such spectra. Despite the traditional opinion that before participation in the chemical binding, the U5f electrons could be promoted to the higher (for example - U6d levels, it was theoretically proved and experimentally confirmed that the U5f electrons (about two U5f electrons are able to participate directly in the chemical bond formation in uranium trioxide. The filled U5f states proved to be localized in the outer valence molecular orbitals energy range 4-9 eV, while the vacant U5f states were generally localized in the low-energy range (0-6 eV above zero. It was experimentally shown that U6p electrons not only participate effectively in the inner valence molecular orbital formation but also participate strongly (more than 1 U6p electron in the formation of die filled outer valence molecular orbitals.

  2. Determination of micro-amount bromide in uranium trioxide by spectrophotometric method

    International Nuclear Information System (INIS)

    The content of bromide in the production of uranium trioxide is one of the most important control factors, so determining it accurately seems important. When uranium trioxide is dissolved in nitric acid, in the presence of AgNO3 solution, micro-amount bromide can be co- precipitated with AgCl. Bromide can be separated by centrifugation from a large amount of UO22+ and other anions. In the existing of KOH and H2O2, AgCl can be changed into free bromide. By adding ammonium molybdate as catalyst, bromide and excessive KBrO3 can react and produce Br2. In the medium of tert-butanol-ethanol, Br2 can react with basic fuchsine and produce a purple compound which is stable, the bromide content is determined by spectrophotometric method. The results show that it is a highly sensitive method with low detection limit. Its apparent molar absorption coefficient κ' is 1.7 x 104 L/(mol·cm). Its detection limit is 9 μg/L and determination limit is 0.13 mg/L. The linear relationship is in the range of 0.2-1.6 mg/L with a correlation coefficient of 0.997. The relative standard deviation is less than 10% after it is determed six times at the same time. For bromide content of 4.00 and 8.00 μg, the bromide recovery obtained are between 94% and 103%. (authors)

  3. Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Shen, Hui; Niu, Qiang; Xu, Mengchuan; Rui, Dongsheng; Xu, Shangzhi; Feng, Gangling; Ding, Yusong; Li, Shugang; Jing, Mingxia

    2016-02-06

    Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (parsenic exposure: inorganic arsenic (iAs), monomethyl arsenic (MMA), dimethyl arsenic (DMA), and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD): 1.00; 95% confidence interval (CI): 0.60-1.40; parsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process.

  4. Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Shen, Hui; Niu, Qiang; Xu, Mengchuan; Rui, Dongsheng; Xu, Shangzhi; Feng, Gangling; Ding, Yusong; Li, Shugang; Jing, Mingxia

    2016-02-01

    Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (parsenic exposure: inorganic arsenic (iAs), monomethyl arsenic (MMA), dimethyl arsenic (DMA), and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD): 1.00; 95% confidence interval (CI): 0.60-1.40; parsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process.

  5. 5-year results comparing mineral trioxide aggregate and adhesive resin composite for root-end sealing in apical surgery

    DEFF Research Database (Denmark)

    von Arx, Thomas; Hänni, Stefan; Jensen, Simon Storgård

    2014-01-01

    observers). Two different methods of root-end preparation and filling (primary study parameters) were to be compared (mineral trioxide aggregate [MTA] vs adhesive resin composite [COMP]) without randomization. RESULTS: A total of 271 patients and teeth from a 1-year follow-up sample of 339 could be re...

  6. Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling.

    Science.gov (United States)

    Li, S G; Xu, S Z; Niu, Q; Ding, Y S; Pang, L J; Ma, R L; Jing, M X; Wang, K; Ma, X M; Feng, G L; Liu, J M; Zhang, X F; Xiang, H L; Li, F

    2016-05-01

    This study aims to investigate the mechanisms involved in the action of lutein (LU) alleviating arsenic-induced reproductive toxicity using mice model. Forty male Kunming mice were received following treatments by gavage: normal saline solution (control), arsenic trioxide (ATO; 5 mg/kg/day), LU (40 mg/kg/day), and ATO + LU (5 mg/kg/day + 40 mg/kg/day). At the end, the mice were killed by cervical dislocation and weighed. Pathological examination was done on the testis. The biomedical parameters including superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. The messenger RNA (mRNA) and protein expression of Nrf2, heme oxygenase 1 (HO-1), glutathione S-transferase (GST), nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1) in testis were detected by real-time polymerase chain reaction and Western blot. We found that there was a decrease in sperm count; testis somatic index; the activities of SOD, GSH, total antioxidative capacity (p treated mice, while there was an increase in the levels of sperm abnormalities, MDA, and 8-OHdG than control (p treated with ATO + LU showed recovery of the measured parameters between those of ATO or saline-treated group. The antagonized interaction between ATO and LU was statistically significant (p treated with ATO + LU also showed greater mRNA expression of Nrf2, HO-1, NQO1, and GST than ATO or saline-treated groups. These findings suggest that LU alleviates reproductive toxicity induced by arsenic in male mice via Nrf2 signaling, which implicates a possible mechanism of LU in preventing the reproductive injury, and elucidates that consuming the rich plant sources of LU will alleviate the reproductive toxicity induced by chemicals.

  7. Arsenic removal by using colloidal adsorption flotation utilizing Fe(OH)3 floc in a dissolved air flotation system; Eliminacion de arsenico mediante flotacion por adsorcion coloidal utilizando floculos de Fe(OH){sub 3} en un sistema de flotacion por aire disuelto

    Energy Technology Data Exchange (ETDEWEB)

    Pavez, O.; Palacios, J. M.; Aguilar, C.

    2009-07-01

    In the present work, the influence of Fe/As ratio on the As removal, from aqueous solutions, applying flotation by colloidal adsorption was studied. Ferric chloride was used as coagulant and dodec il sulfate as collector, and arsenic trioxide was utilized to preparing the solutions. The obtained results show that the highest arsenic removal was accomplished in the range of pH between 4 and 5,5, and the increasing of the initial concentration of Fe(III), increases the removal of arsenic from the solution. However, with the decreasing of the initial concentration of arsenic in the solution, it is required a larger Fe/As ratio for its removal. For solutions containing: 13,73, 1,71 and 0,105 mg/L of arsenic, it was shown that to remove around 95% of the dissolved arsenic, a Fe/As ratios of approximately 6/1, 18/1 and 800/1, respectively, are required. (Author) 31 refs.

  8. Discovery of the Arsenic Isotopes

    CERN Document Server

    Shore, A; Heim, M; Schuh, A; Thoennessen, M

    2009-01-01

    Twenty-nine arsenic isotopes have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  9. Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

    International Nuclear Information System (INIS)

    High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. - Highlights: • Arsenic (As) has been associated with increased cardiovascular disease (CVD) risk. • Little is known about CVD effects at lower levels of As exposure common in the US. • Few have investigated the joint effects of As and smoking on CVD in US adults. • We examine chronic low-level As exposure and smoking in relation to CVD mortality. • Arsenic exposure may increase ischemic heart disease mortality among smokers in US

  10. Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

    Energy Technology Data Exchange (ETDEWEB)

    Farzan, Shohreh F. [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States); Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY (United States); Chen, Yu [Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY (United States); Rees, Judy R.; Zens, M. Scot [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States); Karagas, Margaret R., E-mail: margaret.r.karagas@dartmouth.edu [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States)

    2015-09-01

    High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. - Highlights: • Arsenic (As) has been associated with increased cardiovascular disease (CVD) risk. • Little is known about CVD effects at lower levels of As exposure common in the US. • Few have investigated the joint effects of As and smoking on CVD in US adults. • We examine chronic low-level As exposure and smoking in relation to CVD mortality. • Arsenic exposure may increase ischemic heart disease mortality among smokers in US.

  11. Arsenic removal by lime softening

    DEFF Research Database (Denmark)

    Kaosol, T.; Suksaroj, C.; Bregnhøj, Henrik

    2002-01-01

    This paper focuses on the study of arsenic removal for drinking water by lime softening. The initial arsenic (V) concentration was 500 and 1,000 ug/L in synthetic groundwater. The experiments were performed as batch tests with varying lime dosages and mixing time. For the synthetic groundwater......, arsenic (V) removal increased with increasing lime dosage and mixing time, as well as with the resulting pH. The residual arsenic (V) in all cases was lower than the WHO guideline of 10 ug/L at pH higher than 11.5. Kinetic of arsenic (V) removal can be described by a first-order equation as C1 = C0*e......^-k*t. The relation between the constant (k value) and increasing lime dosage was found to be linear, described by k = 0.0034 (Dlime). The results support a theory from the literature that the arsenic (V) was removed by precipitation af Ca3(AsO4)2. The results obtained in the present study suggest that lime...

  12. Arsenic-resistant bacteria solubilized arsenic in the growth media and increased growth of arsenic hyperaccumulator Pteris vittata L.

    Science.gov (United States)

    Ghosh, Piyasa; Rathinasabapathi, Bala; Ma, Lena Q

    2011-10-01

    The role of arsenic-resistant bacteria (ARB) in arsenic solubilization from growth media and growth enhancement of arsenic-hyperaccumulator Pteris vittata L. was examined. Seven ARB (tolerant to 10 mM arsenate) were isolated from the P. vittata rhizosphere and identified by 16S rRNA sequencing as Pseudomonas sp., Comamonas sp. and Stenotrophomonas sp. During 7-d hydroponic experiments, these bacteria effectively solubilized arsenic from the growth media spiked with insoluble FeAsO₄ and AlAsO₄ minerals (from organic C) by P. vittata may be responsible for As solubilization. Increase in P. vittata root biomass from 1.5-2.2 to 3.4-4.2 g/plant dw by ARB and by arsenic was associated with arsenic-induced plant P uptake. Arsenic resistant bacteria may have potential to enhance phytoremediation of arsenic-contaminated soils by P. vittata. PMID:21840210

  13. Approaches to Increase Arsenic Awareness in Bangladesh: An Evaluation of an Arsenic Education Program

    Science.gov (United States)

    George, Christine Marie; Factor-Litvak, Pam; Khan, Khalid; Islam, Tariqul; Singha, Ashit; Moon-Howard, Joyce; van Geen, Alexander; Graziano, Joseph H.

    2013-01-01

    The objective of this study was to design and evaluate a household-level arsenic education and well water arsenic testing intervention to increase arsenic awareness in Bangladesh. The authors randomly selected 1,000 study respondents located in 20 villages in Singair, Bangladesh. The main outcome was the change in knowledge of arsenic from…

  14. Effect of organic matter amendment, arsenic amendment and water management regime on rice grain arsenic species.

    Science.gov (United States)

    Norton, Gareth J; Adomako, Eureka E; Deacon, Claire M; Carey, Anne-Marie; Price, Adam H; Meharg, Andrew A

    2013-06-01

    Arsenic accumulation in rice grain has been identified as a major problem in some regions of Asia. A study was conducted to investigate the effect of increased organic matter in the soil on the release of arsenic into soil pore water and accumulation of arsenic species within rice grain. It was observed that high concentrations of soil arsenic and organic matter caused a reduction in plant growth and delayed flowering time. Total grain arsenic accumulation was higher in the plants grown in high soil arsenic in combination with high organic matter, with an increase in the percentage of organic arsenic species observed. The results indicate that the application of organic matter should be done with caution in paddy soils which have high soil arsenic, as this may lead to an increase in accumulation of arsenic within rice grains. Results also confirm that flooding conditions substantially increase grain arsenic.

  15. Phytoextraction by arsenic hyperaccumulator Pteris vittata L. from six arsenic-contaminated soils: Repeated harvests and arsenic redistribution

    Energy Technology Data Exchange (ETDEWEB)

    Gonzaga, Maria I.S.; Santos, Jorge A.G. [Department of Soil Chemistry, Universidade Federal da Bahia, Cruz das Almas, 44380000 (Brazil); Ma, Lena Q. [Soil and Water Science Department, University of Florida, 2169 McCarty Hall, Gainesville, FL 32611-0290 (United States)], E-mail: lqma@ifas.ufl.edu

    2008-07-15

    This greenhouse experiment evaluated arsenic removal by Pteris vittata and its effects on arsenic redistribution in soils. P. vittata grew in six arsenic-contaminated soils and its fronds were harvested and analyzed for arsenic in October, 2003, April, 2004, and October, 2004. The soil arsenic was separated into five fractions via sequential extraction. The ferns grew well and took up arsenic from all soils. Fern biomass ranged from 24.8 to 33.5 g plant{sup -1} after 4 months of growth but was reduced in the subsequent harvests. The frond arsenic concentrations ranged from 66 to 6,151 mg kg{sup -1}, 110 to 3,056 mg kg{sup -1}, and 162 to 2,139 mg kg{sup -1} from the first, second and third harvest, respectively. P. vittata reduced soil arsenic by 6.4-13% after three harvests. Arsenic in the soils was primarily associated with amorphous hydrous oxides (40-59%), which contributed the most to arsenic taken up by P. vittata (45-72%). It is possible to use P. vittata to remediate arsenic-contaminated soils by repeatedly harvesting its fronds. - Pteris vittata was effective in continuously removing arsenic from contaminated soils after three repeated harvests.

  16. RARE CASE REPORT OF CHRONIC ARSENIC POISONING

    OpenAIRE

    Mundle; Neelima; Sushrut; Yogesh; Shukan; Shalik; Siddharth

    2014-01-01

    Today, arsenic is primarily used in the produc tion of glass and semiconductors., Arsenic may be found as a water or food contaminant, particularly in shellfish and other seafood, and often contaminates fruits and vegetables, particularly rice

  17. Inorganic arsenic poisoning in pastured feeder lambs

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, H.A.; Crane, M.R.; Tomson, K.

    1971-01-01

    Clinical signs and necropsy findings in a group of feeder lambs were suggestive of inorganic arsenic poisoning. Source of exposure was established and toxic concentrations of arsenic were detected in the tissues. 13 references, 1 table.

  18. Airborne exposure and estimated bioavailability of arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Yager, J.W. [Electric Power Research Inst., Madison, WI (United States); Clewell, H.J. III [ICF Consulting, Fairfax, VA (United States); Hicks, J. [Geomatrix, (United States)

    2000-07-01

    A pilot group of workers were used in a study to determine the relationship between exposure to arsenic present in fly ash particles and urinary excretion of inorganic arsenic and its methylated metabolites. Arsenic was measured in the breathing zone of workers during full shift work schedules and daily urine samples were collected to determine the concentration of arsenic and its metabolites. Airborne particle size distribution samples were collected on six-stage personal cascade impactors. Previous studies of airborne exposure to arsenic in copper smelters predict urinary values nearly three times higher than those seen in exposure to arsenic in fly ash. The results suggest that differences in biological uptake of airborne arsenic probably depend on characteristics such as solubility, particle size and distribution and matrix composition of the arsenic compounds.

  19. RARE CASE REPORT OF CHRONIC ARSENIC POISONING

    Directory of Open Access Journals (Sweden)

    Mundle

    2014-12-01

    Full Text Available Today, arsenic is primarily used in the produc tion of glass and semiconductors., Arsenic may be found as a water or food contaminant, particularly in shellfish and other seafood, and often contaminates fruits and vegetables, particularly rice

  20. Arsenic in contaminated soil and river sediment

    Energy Technology Data Exchange (ETDEWEB)

    Bombach, G. (Freiberg Univ. of Mining and Technology, Inst. of Mineralogy, Geochemistry and Ore Deposits, Freiberg (Germany)); Pierra, A. (Freiberg Univ. of Mining and Technology, Inst. of Mineralogy, Geochemistry and Ore Deposits, Freiberg (Germany)); Klemm, W. (Freiberg Univ. of Mining and Technology, Inst. of Mineralogy, Geochemistry and Ore Deposits, Freiberg (Germany))

    1994-09-01

    Different areas in the Erzgebirge mountains are contaminated by high arsenic concentration which is caused by the occurrence of ore and industrial sources. The study showed clearly a high concentration of arsenic in the surface and under soil (A and B horizons) in the Freiberg district. The distribution of the arsenic concentration in the area, the content of water soluble arsenic, the several oxidation states (As[sup 3+], As[sup 5+]) and the bonding types have been analyzed. (orig.)

  1. When Parasites Are Good for Health: Cestode Parasitism Increases Resistance to Arsenic in Brine Shrimps.

    Science.gov (United States)

    Sánchez, Marta I; Pons, Inès; Martínez-Haro, Mónica; Taggart, Mark A; Lenormand, Thomas; Green, Andy J

    2016-03-01

    Parasites and pollutants can both affect any living organism, and their interactions can be very important. To date, repeated studies have found that parasites and heavy metals or metalloids both have important negative effects on the health of animals, often in a synergistic manner. Here, we show for the first time that parasites can increase host resistance to metalloid arsenic, focusing on a clonal population of brine shrimp from the contaminated Odiel and Tinto estuary in SW Spain. We studied the effect of cestodes on the response of Artemia to arsenic (acute toxicity tests, 24h LC50) and found that infection consistently reduced mortality across a range of arsenic concentrations. An increase from 25°C to 29°C, simulating the change in mean temperature expected under climate change, increased arsenic toxicity, but the benefits of infection persisted. Infected individuals showed higher levels of catalase and glutathione reductase activity, antioxidant enzymes with a very important role in the protection against oxidative stress. Levels of TBARS were unaffected by parasites, suggesting that infection is not associated with oxidative damage. Moreover, infected Artemia had a higher number of carotenoid-rich lipid droplets which may also protect the host through the "survival of the fattest" principle and the antioxidant potential of carotenoids. This study illustrates the need to consider the multi-stress context (contaminants and temperature increase) in which host-parasite interactions occur. PMID:26938743

  2. When Parasites Are Good for Health: Cestode Parasitism Increases Resistance to Arsenic in Brine Shrimps.

    Directory of Open Access Journals (Sweden)

    Marta I Sánchez

    2016-03-01

    Full Text Available Parasites and pollutants can both affect any living organism, and their interactions can be very important. To date, repeated studies have found that parasites and heavy metals or metalloids both have important negative effects on the health of animals, often in a synergistic manner. Here, we show for the first time that parasites can increase host resistance to metalloid arsenic, focusing on a clonal population of brine shrimp from the contaminated Odiel and Tinto estuary in SW Spain. We studied the effect of cestodes on the response of Artemia to arsenic (acute toxicity tests, 24h LC50 and found that infection consistently reduced mortality across a range of arsenic concentrations. An increase from 25°C to 29°C, simulating the change in mean temperature expected under climate change, increased arsenic toxicity, but the benefits of infection persisted. Infected individuals showed higher levels of catalase and glutathione reductase activity, antioxidant enzymes with a very important role in the protection against oxidative stress. Levels of TBARS were unaffected by parasites, suggesting that infection is not associated with oxidative damage. Moreover, infected Artemia had a higher number of carotenoid-rich lipid droplets which may also protect the host through the "survival of the fattest" principle and the antioxidant potential of carotenoids. This study illustrates the need to consider the multi-stress context (contaminants and temperature increase in which host-parasite interactions occur.

  3. Extraction of arsenic from arsenic-containing cobalt and nickel slag and preparation of arsenic-bearing compounds%含砷钴镍渣中砷提取与砷盐制备的资源化利用

    Institute of Scientific and Technical Information of China (English)

    余国林; 张盈; 郑诗礼; 邹兴; 王晓辉; 张懿

    2014-01-01

    the form of sodium arsenate salt from the arsenic-rich leachate via cooling crystallization was established, and the reaction medium could be fully recycled. The crystallization rate was confirmed to reach 88.9%(calculated on the basis of Na3AsO4) upon a direct cooling of the hot leachate down to room temperature. On the basis of redox potentials, the sodium arsenate solution could be further reduced by sulfur dioxide (SO2) gas to arsenite, at a reduction yield of 92%under the suitable conditions. Arsenic trioxide with regular octahedron shape could be prepared successfully from the reduced solution, and further recycled to the purification process to purify the zinc sulfate solution. Also, sodium arsenite solution obtained after the reduction of arsenate could be directly used to purify the zinc sulfate solution. Therefore, the technical scheme of alkaline leaching with pressured oxygen, cooling crystallization, arsenate reduction by SO2 gas, and arsenic trioxide preparation, provides an attractive approach to realize the resource utilization of arsenic-containing cobalt and nickel slag.

  4. Treatment of inflammatory root resorption using mineral trioxide aggregate: A case report

    Directory of Open Access Journals (Sweden)

    Roohollah Sharifi

    2014-01-01

    Full Text Available Introduction: This report presents a case to show inflammatory root resorption can be successfully treated by using mineral trioxide aggregate (MTA. Case Report: A central maxillary incisor of an eight-year-old boy was avulsed associated with crown fracture secondary to a fall. The tooth was stored in ice. Early attempts at pulpal revascularization of the replanted tooth proved unsuccessful. To stop inflammatory root resorption, long-term calcium hydroxide therapy was employed. Despite the use of calcium hydroxide, resorption continued. Subsequent to the failure of that treatment, MTA was used as a root canal filling material. At 20-month follow-up, the tooth was asymptomatic and had clinical signs of ankylosis but external inflammatory root resorption had stopped. Discussion: MTA may be considered as an alternative option for the treatment of continuous external inflammatory root resorption.

  5. Nonsurgical Endodontic Retreatment of Advanced Inflammatory External Root Resorption Using Mineral Trioxide Aggregate Obturation

    Directory of Open Access Journals (Sweden)

    Shivani Utneja

    2012-01-01

    Full Text Available Inflammatory external root resorption is one of the major complications after traumatic dental injury. In this case report, we describe treatment of a maxillary central incisor affected by severe, perforating external root resorption. An 18-year-old patient presented with a previously traumatized, root-filled maxillary central incisor associated with pain and sinus tract. Radiographic examination revealed periradicular lesion involving pathologic resorption of the apical region of the root and lateral root surface both mesially and distally. After removal of the root canal filling, the tooth was disinfected with intracanal triple antibiotic paste for 2 weeks. The antibiotic dressing was then removed, and the entire root canal was filled with mineral trioxide aggregate. The endodontic access cavity was restored with composite resin. After 18 months, significant osseous healing of the periradicular region and lateral periodontium had occurred with arrest of external root resorption, and no clinical symptoms were apparent.

  6. Management of immature teeth with apical infections using mineral trioxide aggregate

    Directory of Open Access Journals (Sweden)

    Sivakumar Nuvvula

    2010-01-01

    Full Text Available Traumatic injuries to the young permanent teeth lead to devitalization of the pulp with concomitant arrest in further development of the immature root of the involved tooth. Hermetic seal of the root canal system during obturation is not possible in such cases, due to the lack of an apical constriction. The traditional management technique in such cases has been apexification involving induction of a calcific barrier at the apex using calcium hydroxide, which in turn facilitates obturation of the root canal. However this becomes complicated when there is persistent infection leading to periapical changes. This case report describes the use of mineral trioxide aggregate (MTA for management of a periapically compromised immature tooth.

  7. Chemical and morphological characteristics of mineral trioxide aggregate and Portland cements.

    Science.gov (United States)

    Khan, Shahbaz; Kaleem, Muhammad; Fareed, Muhammad Amber; Habib, Amir; Iqbal, Kefi; Aslam, Ayesha; Ud Din, Shahab

    2016-01-01

    The purpose of this study was to investigate the chemical composition and particle morphology of white mineral trioxide aggregate (WMTA) and two white Portland cements (CEM 1 and CEM 2). Compositional analysis was performed by energy dispersive X-ray spectroscopy, X-ray fluorescence spectrometry and X-ray diffraction whereas, morphological characteristics were analyzed by scanning electron microscope and Laser scattering particle size distribution analyzer. The elemental composition of WMTA, CEM 1 and CEM 2 were similar except for the presence of higher amounts of bismuth in WMTA. Calcium oxide and silicon oxide constitute the major portion of the three materials whereas, tricalcium silicate was detected as the major mineral phase. The particle size distribution and morphology of WMTA was finer compared to CEM 1 and CEM 2. The three tested materials had relatively similar chemical composition and irregular particle morphologies. PMID:26830831

  8. Dissolution of a mineral trioxide aggregate sealer in endodontic solvents compared to conventional sealers

    Directory of Open Access Journals (Sweden)

    Hanan ALZRAIKAT

    2016-01-01

    Full Text Available Abstract The aim of this study is to evaluate the solubility of a Mineral Trioxide Aggregate sealer (MTA-Fillapex compared with five other sealers, calcium hydroxide (Sealapex, resin (Realseal, zinc oxide-eugenol (Tubli-Seal, and two epoxy resins (AH-26 and AH-Plus, in chloroform and eucalyptoil in static and ultrasonic environments. Samples of each sealer were prepared (n = 180 and then divided into 12 groups that were immersed in solvents for 5 and 10 min in static and ultrasonic environments. The mean weight loss was determined, and the values were compared using Student’s t-test, One-way ANOVA, and Tukey’s HSD post-hoc test (p 0.05. In conclusion, MTA-Fillapex was not sufficiently dissolved in either solvent. Ultrasonic activation had limited effectiveness on MTA-Fillapex dissolution, whereas it significantly increased the efficiency of solvents in dissolving a number of endodontic sealers.

  9. Management of External Invasive Cervical Resorption Tooth with Mineral Trioxide Aggregate: A Case Report

    Directory of Open Access Journals (Sweden)

    Anuja Ikhar

    2013-01-01

    Full Text Available Invasive cervical resorption is entirely uncommon entities and the etiology is poorly understood. A 19 year old patient presented with fractured upper left central incisor and sinus tract opening on the distobuccal aspect in cervical region. Radiographic examination shows irregular radiolucency over the coronal one-third and it extended externally towards the external invasive resorption. After sectional obturation, the defect was accessed surgically. The resorption area was chemomechanically debrided using irrigant solution. Fibre post placement using flowable composite resin and Mineral Trioxide Aggregate (MTA was used to fill the resorptive defect, and the coronal access was temporarily sealed. Composite restoration was subsequently replaced with ceramic crown after 4 years. Radiographs at 1 and 4 years showed adequate repair of the resorption and endodontic success. Clinically and radiographically the tooth was asymptomatic, and no periodontal pocket was found after a 4-year followup.

  10. Cytotoxic effects of mineral trioxide aggregate, calcium enrichedmixture cement, Biodentine and octacalcium pohosphate onhuman gingival fibroblasts

    Science.gov (United States)

    A. Saberi, Eshagh; Farhadmollashahi, Narges; Ghotbi, Faroogh; Karkeabadi, Hamed; Havaei, Roholla

    2016-01-01

    Background. This in vitro study compared the effects of mineral trioxide aggregate (MTA), calcium enriched mixture(CEM) cement, Biodentine (BD) and octacalcium phosphate (OCP) on the viability of human gingival fibroblasts (HGFs). Methods. After completion of the setting time of the materials under study, fibroblasts were placed in 24-well insert platesand 1 mg of each material was added to the respective wells. The plates were then incubated at 37°C. The inserts were removedat 24, 48 and 168 hours and 2,5-diphenyltetrazolium bromide was added to assess cytotoxicity via the MTT colorimetricassay. Data were analyzed at different time intervals using repeated-measures ANOVA, followed by the Bonferronitest at three levels of significance of P MTA (P MTA, CEM, Biodentine and OCP against HGFs was similar to that of the control group at 24and 48 hours. Over time, MTA and Biodentine exhibited less cytotoxicity than other materials. PMID:27429722

  11. AC conductivity and dielectric properties of bulk tungsten trioxide (WO{sub 3})

    Energy Technology Data Exchange (ETDEWEB)

    El-Nahass, M.M. [Department of Physics, Faculty of Education, Ain Shams University, Roxy 11757, Cairo (Egypt); Ali, H.A.M., E-mail: hend2061@yahoo.com [Department of Physics, Faculty of Education, Ain Shams University, Roxy 11757, Cairo (Egypt); Saadeldin, M.; Zaghllol, M. [Physics Department, Faculty of Science, Cairo University, Giza 12613 (Egypt)

    2012-11-15

    AC conductivity and dielectric properties of tungsten trioxide (WO{sub 3}) in a pellet form were studied in the frequency range from 42 Hz to 5 MHz with a variation of temperature in the range from 303 K to 463 K. AC conductivity, {sigma}{sub ac}({omega}) was found to be a function of {omega}{sup s} where {omega} is the angular frequency and s is the frequency exponent. The values of s were found to be less than unity and decrease with increasing temperature, which supports the correlated barrier hopping mechanism (CBH) as the dominant mechanism for the conduction in WO{sub 3}. The dielectric constant ({epsilon} Prime ) and dielectric loss ({epsilon} Double-Prime ) were measured. The Cole-Cole diagram determined complex impedance for different temperatures.

  12. Theoretical study of partial oxidation of ethylene by vanadium trioxide cluster cation

    Institute of Scientific and Technical Information of China (English)

    WANG ZheChen; DING XunLei; MA YanPing; CAO Hai; WU XiaoNan; ZHAO YanXia; HE ShengGui

    2009-01-01

    Density functional theory (DFT) study of reaction between vanadium trioxide cluster cation (VO+3) and ethylene (C2H4) to yield VO+2 + CH3CHO (acetaldehyde) and VO2CH+2 + HCHO (formaldehyde) is carried out.Structures of all reactants,products,intermediates,and transition state in the reaction have been optimized and characterized.The results show unexpected barriers in the reaction due to the existence of a η2-O2 moiety in the ground state structure of VO+3.The initial reaction steps combining ethylene adsorption,C=C activation and O-O cleavage are proposed as rate limiting processes.Comparison of reactions of VO+3 + C2H4 with VO3 + C2H4 and VO+2 + C2H4 in the previous studies is made in detail.The results of this work may shed light on the understanding of C=C bond cleavage in related heterogeneous catalysis.

  13. Mutagenic effects of chromium trioxide on root tip cells of Vicia faba

    Institute of Scientific and Technical Information of China (English)

    钱晓薇

    2004-01-01

    In this study on the mutagenic effects of different concentrations of chromium trioxide (CrO3) on Vicia faba root tip, micronucleus assay and chromosome aberration assay were used to determine the mitotic indexes, micronucleus rate and chromosome aberration rate of Viciafaba root tip cells. The results showed that the effects of CrO3 concentration on the mitotic indexes were complicated. CrO3 increases the micronucleus rate of Vicia faba root tip cells. It was found that within certain range of CrO3 concentration the micronucleus rate increased systematically with increased concentration of CrO3, but that the micronucleus rate decreased at higher level of CrO3 and that CrO3 also caused various types of chromosome aberration at a rate which increased systematically with increased concentration of CrO3. We concluded that CrO3 has significant mutagenic effect on Viciafaba root tip cells.

  14. Mutagenic effects of chromium trioxide on root tip cells of Vicia faba

    Institute of Scientific and Technical Information of China (English)

    钱晓徽

    2004-01-01

    In this study on the mutagenic effects of different concentrations of chromium trioxide (CrO3) on Vicia faba root tip, micronucleus assay and chromosome aberration assay were used to determine the mitotic indexes, micronucleus rate and chromosome aberration rate of Vicia faba root tip cells. The results showed that the effects of CrO3 concentration on the mitotic indexes were complicated. CrO3 increases the micronucleus rate of Vicia faba root tip cells. It was found that within certain range of CrO3 concentration the micronucleus rate increased systematically with increased concentration of CrO3, but that the micronucleus rate decreased at higher level of CrO3 and that CrO3 also caused various types of chromosome aberration at a rate which increased systematically with increased concentration of CrO3. We concluded that CrO3 has significant mutagenic effect on Vicia faba root tip cells.

  15. Conservative Management of Unset Mineral Trioxide Aggregate Root-End Filling: A Case Report.

    Science.gov (United States)

    Parirokh, Masoud; Farzaneh, Sedigheh; Hallajmofrad, Ali Reza

    2016-01-01

    This case report presents conservative management of unset mineral trioxide aggregate (MTA) after being placed as a root-end filling material following periapical surgery. Periapical surgery was indicated for a maxillary lateral incisor of a 15-year-old male due to persistent exudate and a large periapical lesion. During surgery Angelus MTA was placed as root-end filling. The next session it was noticed that MTA had failed to completely set. In an orthograde approach, calcium-enriched mixture (CEM) cement was used to obturate the root canal space. The patient was followed up for 27 months and did not exhibit any clinical signs and symptoms. Radiographic images showed complete healing of the lesion. PMID:27471540

  16. Arsenic - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Arsenic URL of this page: https://medlineplus.gov/languages/arsenic.html Other topics A-Z A B C ... V W XYZ List of All Topics All Arsenic - Multiple Languages To use the sharing features on ...

  17. 21 CFR 556.60 - Arsenic.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Arsenic. 556.60 Section 556.60 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND... New Animal Drugs § 556.60 Arsenic. Tolerances for total residues of combined arsenic (calculated as...

  18. 29 CFR 1910.1018 - Inorganic arsenic.

    Science.gov (United States)

    2010-07-01

    ... container in the change-room which prevents dispersion of inorganic arsenic outside the container. (vi) The... readily through the skin. Because inorganic arsenic is a poison, you should wash your hands thoroughly... 29 Labor 6 2010-07-01 2010-07-01 false Inorganic arsenic. 1910.1018 Section 1910.1018...

  19. Chloride sublimation of gold-arsenic concentrates

    International Nuclear Information System (INIS)

    Present article is devoted to chloride sublimation of gold-arsenic concentrates. The results of studies of chloride sublimation of gold-arsenic comprising concentrates of Chore deposit of Tajikistan are considered. It is found that by application sodium chloride for gold-arsenic comprising concentrates it is possible to extract gold and silver from flotation concentrates.

  20. Arsenic intoxication associated with tubulointerstitial nephritis.

    Science.gov (United States)

    Prasad, G V; Rossi, N F

    1995-08-01

    Arsenic poisoning is an often unrecognized cause of renal insufficiency. We report a case of tubulointerstitial nephritis associated with an elevated urinary arsenic concentration. Removal of the putative source of arsenic resulted in symptomatic improvement, resolution of abnormal abdominal radiographs, and stabilization of renal function. This case emphasizes the importance of heavy metal screening in patients with multisystem complaints and tubulointerstitial nephritis.

  1. Arsenic – Poison or medicine?

    Directory of Open Access Journals (Sweden)

    Karolina Kulik-Kupka

    2016-04-01

    Full Text Available Arsenic (As is commonly known as a poison. Only a few people know that As has also been widely used in medicine. In the past years As and its compounds were used as a medicine for the treatment of such diseases as diabetes, psoriasis, syphilis, skin ulcers and joint diseases. Nowadays As is also used especially in the treatment of patients with acute promyelocytic leukemia. The International Agency for Research on Cancer (IARC has recognized arsenic as an element with carcinogenic effect evidenced by epidemiological studies, but as previously mentioned it is also used in the treatment of neoplastic diseases. This underlines the specificity of the arsenic effects. Arsenic occurs widely in the natural environment, for example, it is present in soil and water, which contributes to its migration to food products. Long exposure to this element may lead to liver damages and also to changes in myocardium. Bearing in mind that such serious health problems can occur, monitoring of the As presence in the environmental media plays a very important role. In addition, the occupational risk of As exposure in the workplace should be identified and checked. Also the standards for As presence in food should be established. This paper presents a review of the 2015 publications based on the Medical database like PubMed and Polish Medical Bibliography. It includes the most important information about arsenic in both forms, poison and medicine. Med Pr 2016;67(1:89–96

  2. Mineral resource of the month: arsenic

    Science.gov (United States)

    Brooks, William E.

    2008-01-01

    Arsenic has a long and varied history: Although it was not isolated as an element until the 13th century, it was known to the ancient Chinese, Egyptians and Greeks in compound form in the minerals arsenopyrite, realgar and orpiment. In the 1400s, “Scheele’s Green” was first used as an arsenic pigment in wallpaper, and leached arsenic from wallpaper may have contributed to Napoleon’s death in 1821. The 1940s play and later movie, Arsenic and Old Lace, dramatizes the metal’s more sinister role. Arsenic continues to be an important mineral commodity with many modern applications.

  3. Modelling synergistic effects of appetite regulating hormones

    DEFF Research Database (Denmark)

    Schmidt, Julie Berg; Ritz, Christian

    2016-01-01

    We briefly reviewed one definition of dose addition, which is applicable within the framework of generalized linear models. We established how this definition of dose addition corresponds to effect addition in case only two doses per compound are considered for evaluating synergistic effects. The....... The link between definitions was exemplified for an appetite study where two appetite hormones were studied....

  4. Arsenic contamination in food-chain: transfer of arsenic into food materials through groundwater irrigation.

    Science.gov (United States)

    Huq, S M Imamul; Joardar, J C; Parvin, S; Correll, Ray; Naidu, Ravi

    2006-09-01

    Arsenic contamination in groundwater in Bangladesh has become an additional concern vis-à-vis its use for irrigation purposes. Even if arsenic-safe drinking-water is assured, the question of irrigating soils with arsenic-laden groundwater will continue for years to come. Immediate attention should be given to assess the possibility of accumulating arsenic in soils through irrigation-water and its subsequent entry into the food-chain through various food crops and fodders. With this possibility in mind, arsenic content of 2,500 water, soil and vegetable samples from arsenic-affected and arsenic-unaffected areas were analyzed during 1999-2004. Other sources of foods and fodders were also analyzed. Irrigating a rice field with groundwater containing 0.55 mg/L of arsenic with a water requirement of 1,000 mm results in an estimated addition of 5.5 kg of arsenic per ha per annum. Concentration of arsenic as high as 80 mg per kg of soil was found in an area receiving arsenic-contaminated irrigation. A comparison of results from affected and unaffected areas revealed that some commonly-grown vegetables, which would usually be suitable as good sources of nourishment, accumulate substantially-elevated amounts of arsenic. For example, more than 150 mg/kg of arsenic has been found to be accumulated in arum (kochu) vegetable. Implications of arsenic ingested in vegetables and other food materials are discussed in the paper. PMID:17366772

  5. An ex-vivo comparative study of root-end marginal adaptation using grey mineral trioxide aggregate, white mineral trioxide aggregate, and Portland cement under scanning electron microscopy

    Science.gov (United States)

    Baranwal, Akash Kumar; Paul, Mohan L.; Mazumdar, Dibyendu; Adhikari, Haridas Das; Vyavahare, Nishant K.; Jhajharia, Kapil

    2015-01-01

    Context: Where nonsurgical endodontic intervention is not possible, or it will not solve the problem, surgical endodontic treatment must be considered. A major cause of surgical endodontic failures is an inadequate apical seal, so the use of the suitable substance as root-end filling material that prevents egress of potential contaminants into periapical tissue is very critical. Aims: The aim of the present ex-vivo study was to compare and evaluate the three root-end filling materials of mineral trioxide aggregate (MTA) family (white MTA [WMTA], grey MTA [GMTA] and Portland cement [PC]) for their marginal adaptation at the root-end dentinal wall using scanning electron microscopy (SEM). Materials and Methods: Sixty human single-rooted teeth were decoronated, instrumented, and obturated with Gutta-percha. After the root-end resection and apical cavity preparation, the teeth were randomly divided into three-experimental groups (each containing 20 teeth) and each group was filled with their respective experimental materials. After longitudinal sectioning of root, SEM examination was done to determine the overall gap between retrograde materials and cavity walls in terms of length and width of the gap (maximum) at the interface. Descriptive statistical analysis was performed to calculate the means with corresponding standard errors, median and ranges along with an analysis of variance and Tukey's test. Results: The least overall gap was observed in GMTA followed by PC and WMTA. While after statistically analyzing the various data obtained from different groups, there was no significant difference among these three groups in terms of marginal adaptation. Conclusion: GMTA showed the best overall adaptation to root dentinal wall compared to PC and WMTA. Being biocompatible and cheaper, the PC may be an alternative but not a substitute for MTA. PMID:26430305

  6. An ex-vivo comparative study of root-end marginal adaptation using grey mineral trioxide aggregate, white mineral trioxide aggregate, and Portland cement under scanning electron microscopy

    Directory of Open Access Journals (Sweden)

    Akash Kumar Baranwal

    2015-01-01

    Full Text Available Context: Where nonsurgical endodontic intervention is not possible, or it will not solve the problem, surgical endodontic treatment must be considered. A major cause of surgical endodontic failures is an inadequate apical seal, so the use of the suitable substance as root-end filling material that prevents egress of potential contaminants into periapical tissue is very critical. Aims: The aim of the present ex-vivo study was to compare and evaluate the three root-end filling materials of mineral trioxide aggregate (MTA family (white MTA [WMTA], grey MTA [GMTA] and Portland cement [PC] for their marginal adaptation at the root-end dentinal wall using scanning electron microscopy (SEM. Materials and Methods: Sixty human single-rooted teeth were decoronated, instrumented, and obturated with Gutta-percha. After the root-end resection and apical cavity preparation, the teeth were randomly divided into three-experimental groups (each containing 20 teeth and each group was filled with their respective experimental materials. After longitudinal sectioning of root, SEM examination was done to determine the overall gap between retrograde materials and cavity walls in terms of length and width of the gap (maximum at the interface. Descriptive statistical analysis was performed to calculate the means with corresponding standard errors, median and ranges along with an analysis of variance and Tukey′s test. Results: The least overall gap was observed in GMTA followed by PC and WMTA. While after statistically analyzing the various data obtained from different groups, there was no significant difference among these three groups in terms of marginal adaptation. Conclusion: GMTA showed the best overall adaptation to root dentinal wall compared to PC and WMTA. Being biocompatible and cheaper, the PC may be an alternative but not a substitute for MTA.

  7. Arsenic-cadmium interaction in rats.

    Science.gov (United States)

    Díaz-Barriga, F; Llamas, E; Mejía, J J; Carrizales, L; Santoyo, M E; Vega-Vega, L; Yáñez, L

    1990-11-01

    Simultaneous exposure to cadmium and arsenic is highly probable in the urban area of San Luis Potosi, Mexico due to common localization of copper and zinc smelters. Therefore, in this work, rats were intraperitoneally exposed either to cadmium or arsenic alone, or simultaneously to both metals. The effects of these treatments on three different toxicological parameters were studied. Cadmium modified the LD50 of arsenic and conversely arsenic modified the LD50 for cadmium. At the histopathological level, arsenic appeared to protect against the cadmium effects, especially on testes. This protective effect seemed to be related to the glutathione levels found in this tissue: rats exposed to both arsenic and cadmium, presented glutathione values intermediate to those observed after exposure to either metal alone; arsenic had the highest value and cadmium the lowest. In liver, rats exposed to arsenic, cadmium or arsenic and cadmium, presented glutathione values below those in the saline group, with the lowest value corresponding to the arsenic and cadmium treatment. The results appear to support the proposed interaction between arsenic and cadmium and coexposure to both metals seems to alter certain effects produced by either metal alone. PMID:2219140

  8. Arsenic occurrence in New Hampshire drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Peters, S.C.; Blum, J.D.; Klaue, B. [Dartmouth Coll., Hanover, NH (United States). Dept. of Earth Sciences; Karagas, M.R. [Dartmouth Medical School, Hanover, NH (United States). Dept. of Community and Family Medicine

    1999-05-01

    Arsenic concentrations were measured in 992 drinking water samples collected from New Hampshire households using online hydride generation ICP-MS. These randomly selected household water samples contain much less arsenic than those voluntarily submitted for analysis to the New Hampshire Department of Environmental Services (NHDES). Extrapolation of the voluntarily submitted sample set to all New Hampshire residents significantly overestimates arsenic exposure. In randomly selected households, concentrations ranged from <0.0003 to 180 {micro}g/L, with water from domestic wells containing significantly more arsenic than water from municipal sources. Water samples from drilled bedrock wells had the highest arsenic concentrations, while samples from surficial wells had the lowest arsenic concentrations. The authors suggest that much of the groundwater arsenic in New Hampshire is derived from weathering of bedrock materials and not from anthropogenic contamination. The spatial distribution of elevated arsenic concentrations correlates with Late-Devonian Concord-type granitic bedrock. Field observations in the region exhibiting the highest groundwater arsenic concentrations revealed abundant pegmatite dikes associated with nearby granites. Analysis of rock digests indicates arsenic concentrations up to 60 mg/kg in pegmatites, with much lower values in surrounding schists and granites. Weak acid leaches show that approximately half of the total arsenic in the pegmatites is labile and therefore can be mobilized during rock-water interaction.

  9. Linking Microbial Activity with Arsenic Fate during Cow Dung Disposal of Arsenic-Bearing Wastes

    Science.gov (United States)

    Clancy, T. M.; Reddy, R.; Tan, J.; Hayes, K. F.; Raskin, L.

    2014-12-01

    To address widespread arsenic contamination of drinking water sources numerous technologies have been developed to remove arsenic. All technologies result in the production of an arsenic-bearing waste that must be evaluated and disposed in a manner to limit the potential for environmental release and human exposure. One disposal option that is commonly recommended for areas without access to landfills is the mixing of arsenic-bearing wastes with cow dung. These recommendations are made based on the ability of microorganisms to create volatile arsenic species (including mono-, di-, and tri-methylarsine gases) to be diluted in the atmosphere. However, most studies of environmental microbial communities have found only a small fraction (arsenic present in soils or rice paddies is released via volatilization. Additionally, past studies often have not monitored arsenic release in the aqueous phase. Two main pathways for microbial arsenic volatilization are known and include methylation of arsenic during methanogenesis and methylation by arsenite S-adenosylmethionine methyltransferase. In this study, we compare the roles of these two pathways in arsenic volatilization and aqueous mobilization through mesocosm experiments with cow dung and arsenic-bearing wastes produced during drinking water treatment in West Bengal, India. Arsenic in gaseous, aqueous, and solid phases was measured. Consistent with previous reports, less than 0.02% of the total arsenic present was volatilized. A much higher amount (~5%) of the total arsenic was mobilized into the liquid phase. Through the application of molecular tools, including 16S rRNA sequencing and quantification of gene transcripts involved in methanogenesis, this study links microbial community activity with arsenic fate in potential disposal environments. These results illustrate that disposal of arsenic-bearing wastes by mixing with cow dung does not achieve its end goal of promoting arsenic volatilization but rather appears to

  10. Histopathologic Responses of Dog’s Dental Pulp to Mineral Trioxide Aggregate, Bio Active Glass, Formocresol, Hydroxyapatite

    OpenAIRE

    Neda Ahmadi; Sayed Mohammad Razavi; Ebrahim Jabbarifar

    2007-01-01

    Introduction: Bio Active Glass (BAG) is often used as a filler material for regeneration of dental bone defects. Mineral trioxide aggregate (MTA) is used as retrofilling agent, repair of root resorption and pulpotomy agent in primary dentition. Formocresol (FC) is old and standard fixation agent in pulpotomy procedures. Hydroxyapatite (HA) is a biologic constitute. It is used in ridge augmentation, bony defect repair and pulpotomy agent in teeth. The purpose of this study was evaluation of hi...

  11. Fluoride and arsenic exposure impairs learning and memory and decreases mGluR5 expression in the hippocampus and cortex in rats.

    Directory of Open Access Journals (Sweden)

    Shoufang Jiang

    Full Text Available Fluoride and arsenic are two common inorganic contaminants in drinking water that are associated with impairment in child development and retarded intelligence. The present study was conducted to explore the effects on spatial learning, memory, glutamate levels, and group I metabotropic glutamate receptors (mGluRs expression in the hippocampus and cortex after subchronic exposure to fluoride, arsenic, and a fluoride and arsenic combination in rats. Weaned male Sprague-Dawley rats were assigned to four groups. The control rats drank tap water. Rats in the three exposure groups drank water with sodium fluoride (120 mg/L, sodium arsenite (70 mg/L, and a sodium fluoride (120 mg/L and sodium arsenite (70 mg/L combination for 3 months. Spatial learning and memory was measured in Morris water maze. mGluR1 and mGluR5 mRNA and protein expression in the hippocampus and cortex was detected using RT-PCR and Western blot, respectively. Compared with controls, learning and memory ability declined in rats that were exposed to fluoride and arsenic both alone and combined. Combined fluoride and arsenic exposure did not have a more pronounced effect on spatial learning and memory compared with arsenic and fluoride exposure alone. Compared with controls, glutamate levels decreased in the hippocampus and cortex of rats exposed to fluoride and combined fluoride and arsenic, and in cortex of arsenic-exposed rats. mGluR5 mRNA and protein expressions in the hippocampus and mGluR5 protein expression in the cortex decreased in rats exposed to arsenic alone. Interestingly, compared with fluoride and arsenic exposure alone, fluoride and arsenic combination decreased mGluR5 mRNA expression in the cortex and protein expression in the hippocampus, suggesting a synergistic effect of fluoride and arsenic. These data indicate that fluoride and arsenic, either alone or combined, can decrease learning and memory ability in rats. The mechanism may be associated with changes of

  12. Managing hazardous pollutants in Chile: arsenic.

    Science.gov (United States)

    Sancha, Ana María; O'Ryan, Raul

    2008-01-01

    Chile is one of the few countries that faces the environmental challenge posed by extensive arsenic pollution, which exists in the northern part of the country. Chile has worked through various options to appropriately address the environmental challenge of arsenic pollution of water and air. Because of cost and other reasons, copying standards used elsewhere in the world was not an option for Chile. Approximately 1.8 million people, representing about 12% of the total population of the country, live in arsenic-contaminated areas. In these regions, air, water, and soil are contaminated with arsenic from both natural and anthropogenic sources. For long periods, water consumed by the population contained arsenic levels that exceeded values recommended by the World Health Organization. Exposure to airborne arsenic also occurred near several large cities, as a consequence of both natural contamination and the intensive mining activity carried out in those areas. In rural areas, indigenous populations, who lack access to treated water, were also exposed to arsenic by consuming foods grown locally in arsenic-contaminated soils. Health effects in children and adults from arsenic exposure first appeared in the 1950s. Such effects included vascular, respiratory, and skin lesions from intake of high arsenic levels in drinking water. Methods to remove arsenic from water were evaluated, developed, and implemented that allowed significant reductions in exposure at a relatively low cost. Construction and operation of treatment plants to remove arsenic from water first began in the 1970s. Beginning in the 1990s, epidemiological studies showed that the rate of lung and bladder cancer in the arsenic-polluted area was considerably higher than mean cancer rates for the country. Cancer incidence was directly related to arsenic exposure. During the 1990s, international pressure and concern by Chile's Health Ministry prompted action to regulate arsenic emissions from copper smelters. A

  13. Speciation analysis of arsenic in groundwater from Inner Mongolia with an emphasis on acid-leachable particulate arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Gong Zhilong [Department of Public Health Sciences, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alta., T6G 2G3 (Canada); Lu Xiufen [Department of Public Health Sciences, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alta., T6G 2G3 (Canada); Watt, Corinna [Department of Public Health Sciences, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alta., T6G 2G3 (Canada); Wen Bei [Department of Public Health Sciences, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alta., T6G 2G3 (Canada); He Bin [Department of Public Health Sciences, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alta., T6G 2G3 (Canada); Mumford, Judy [National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Human Studies Division, Epidemiology and Biomarkers Branch, Research Triangle Park, NC 27711 (United States); Ning Zhixiong [Ba Men Anti-Epidemic Station, Lin He, Inner Mongolia (China); Xia Yajuan [Inner Mongolia Center for Endemic Disease Control and Research, Huhhot, Inner Mongolia (China); Le, X. Chris [Department of Public Health Sciences, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alta., T6G 2G3 (Canada)]. E-mail: xc.le@ualberta.ca

    2006-01-05

    Arsenic in drinking water affects millions of people around the world. While soluble arsenic is commonly measured, the amount of particulate arsenic in drinking water has often been overlooked. We report here determination of the acid-leachable particulate arsenic and soluble arsenicals in well water from an arsenic-poisoning endemic area in Inner Mongolia, China. Water samples (583) were collected from 120 wells in Ba Men, Inner Mongolia, where well water was the primary drinking water source. Two methods were demonstrated for the determination of soluble arsenic species (primarily inorganic arsenate and arsenite) and total particulate arsenic. The first method used solid phase extraction cartridges and membrane filters to separate arsenic species on-site, followed by analysis of the individual arsenic species eluted from the cartridges and filters. The other method uses liquid chromatography separation with hydride generation atomic fluorescence detection to determine soluble arsenic species. Analysis of acidified water samples using inductively coupled plasma mass spectrometry provided the total arsenic concentration. Arsenic concentrations in water samples from the 120 wells ranged from <1 to {approx}1000 {mu}g L{sup -1}. On average, particulate arsenic accounted for 39 {+-} 38% (median 36%) of the total arsenic. In some wells, particulate arsenic was six times higher than the soluble arsenic concentration. Particulate arsenic can be effectively removed using membrane filtration. The information on particulate and soluble arsenic in water is useful for optimizing treatment options and for understanding the geochemical behavior of arsenic in groundwater.

  14. Mineral sources and transport pathways for arsenic release in a coastal watershed, USA

    Science.gov (United States)

    Foley, Nora K.; Ayuso, Robert A.

    2008-01-01

    Metasedimentary bedrock of coastal Maine contains a diverse suite of As-bearing minerals that act as significant sources of elements found in ground and surface waters in the region. Arsenic sources in the Penobscot Formation include, in order of decreasing As content by weight: löllingite and realgar (c.70%), arsenopyrite, cobaltite, glaucodot, and gersdorffite (in the range of 34–45%), arsenian pyrite ( glaucodot, arsenopyrite-cobaltian > arsenopyrite, cobaltite, gersdorffite, fine-grained pyrite, Ni-pyrite > coarse-grained pyrite. Reactions illustrate that oxidation of Fe-As disulphide group and As-sulphide minerals is the primary release process for As. Liberation of As by carbonation of realgar and orpiment in contact with high-pH groundwaters may contribute locally to elevated contents of As in groundwater, especially where As is decoupled from Fe. Released metals are sequestered in secondary minerals by sorption or by incorporation in crystal structures. Secondary minerals acting as intermediate As reservoirs include claudetite (c.75%), orpiment (61%), scorodite (c. 45%), secondary arsenopyrite (c. 46%), goethite (<4490 ppm), natrojarosite (<42 ppm), rosenite, melanterite, ferrihydrite, and Mn-hydroxide coatings. Some soils also contain Fe-Co-Ni-arsenate, Ca-arsenate, and carbonate minerals. Reductive dissolution of Fe-oxide minerals may govern the ultimate release of iron and arsenic – especially As(V) – to groundwater; however, dissolution of claudetite (arsenic trioxide) may directly contribute As(III). Processes thought to explain the release of As from minerals in bedrock include oxidation of arsenian pyrite or arsenopyrite, or carbonation of As-sulphides, and most models based on these generally rely on discrete minerals or on a fairly limited series of minerals. In contrast, in the Penobscot Formation and other metasedimentary rocks of coastal Maine, oxidation of As-bearing Fe-cobalt-nickel-sulphide minerals, dissolution (by reduction) of

  15. Effects of plant arsenic uptake and heavy metals on arsenic distribution in an arsenic-contaminated soil

    Energy Technology Data Exchange (ETDEWEB)

    Fayiga, Abioye O. [Soil and Water Science Department, University of Florida, Gainesville, FL 32611-0290 (United States); Ma, Lena Q. [Soil and Water Science Department, University of Florida, Gainesville, FL 32611-0290 (United States) and Key Laboratory of Terrestrial Ecological Process, Chinese Academy of Sciences, Shenyang 110016 (China)]. E-mail: lqma@ifas.ufl.edu; Zhou Qixing [Key Laboratory of Terrestrial Ecological Process, Chinese Academy of Sciences, Shenyang 110016 (China)

    2007-06-15

    This study examined the effects of heavy metals and plant arsenic uptake on soil arsenic distribution. Chemical fractionation of an arsenic-contaminated soil spiked with 50 or 200 mg kg{sup -1} Ni, Zn, Cd or Pb was performed before and after growing the arsenic hyperaccumulator Pteris vittata L for 8 weeks using NH{sub 4}Cl (water-soluble plus exchangeable, WE-As), NH{sub 4}F (Al-As), NaOH (Fe-As), and H{sub 2}SO{sub 4} (Ca-As). Arsenic in the soil was present primarily as the recalcitrant forms with Ca-As being the dominant fraction (45%). Arsenic taken up by P. vittata was from all fractions though Ca-As contributed the most (51-71% reduction). After 8 weeks of plant growth, the Al-As and Fe-As fractions were significantly (p < 0.01) greater in the metal-spiked soils than the control, with changes in the WE-As fraction being significantly (p = 0.007) correlated with plant arsenic removal. The plant's ability to solubilize soil arsenic from recalcitrant fractions may have enhanced its ability to hyperaccumulate arsenic. - Arsenic taken up by P. vittata was from all fractions with most from the Ca-fraction.

  16. Urinary Arsenic Metabolites of Subjects Exposed to Elevated Arsenic Present in Coal in Shaanxi Province, China

    Directory of Open Access Journals (Sweden)

    Linsheng Yang

    2011-06-01

    Full Text Available In contrast to arsenic (As poisoning caused by naturally occurring inorganic arsenic-contaminated water consumption, coal arsenic poisoning (CAP induced by elevated arsenic exposure from coal combustion has rarely been reported. In this study, the concentrations and distributions of urinary arsenic metabolites in 57 volunteers (36 subjects with skin lesions and 21 subjects without skin lesions, who had been exposed to elevated levels of arsenic present in coal in Changshapu village in the south of Shaanxi Province (China, were reported. The urinary arsenic species, including inorganic arsenic (iAs [arsenite (iAsIII and arsenate (iAsV], monomethylarsonic acid (MMAV and dimethylarsinic acid (DMAV, were determined by high-performance liquid chromatography (HPLC combined with inductively coupled plasma mass spectroscopy (ICP-MS. The relative distributions of arsenic species, the primary methylation index (PMI = MMAV/iAs and the secondary methylation index (SMI = DMAV/MMAV were calculated to assess the metabolism of arsenic. Subjects with skin lesions had a higher concentration of urinary arsenic and a lower arsenic methylation capability than subjects without skin lesions. Women had a significantly higher methylation capability of arsenic than men, as defined by a higher percent DMAV and SMI in urine among women, which was the one possible interpretation of women with a higher concentration of urinary arsenic but lower susceptibility to skin lesions. The findings suggested that not only the dose of arsenic exposure but also the arsenic methylation capability have an impact on the individual susceptibility to skin lesions induced by coal arsenic exposure.

  17. Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China

    Energy Technology Data Exchange (ETDEWEB)

    Liu, J.; Zheng, B.S.; Aposhian, H.V.; Zhou, Y.S.; Chen, M.L.; Zhang, A.H.; Waalkes, M.P. [NIEHS, Research Triangle Park, NC (USA)

    2002-07-01

    Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China was investigated. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such over exposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area.

  18. Linking Microbial Activity with Arsenic Fate during Cow Dung Disposal of Arsenic-Bearing Wastes

    Science.gov (United States)

    Clancy, T. M.; Reddy, R.; Tan, J.; Hayes, K. F.; Raskin, L.

    2014-12-01

    To address widespread arsenic contamination of drinking water sources numerous technologies have been developed to remove arsenic. All technologies result in the production of an arsenic-bearing waste that must be evaluated and disposed in a manner to limit the potential for environmental release and human exposure. One disposal option that is commonly recommended for areas without access to landfills is the mixing of arsenic-bearing wastes with cow dung. These recommendations are made based on the ability of microorganisms to create volatile arsenic species (including mono-, di-, and tri-methylarsine gases) to be diluted in the atmosphere. However, most studies of environmental microbial communities have found only a small fraction (cow dung and arsenic-bearing wastes produced during drinking water treatment in West Bengal, India. Arsenic in gaseous, aqueous, and solid phases was measured. Consistent with previous reports, less than 0.02% of the total arsenic present was volatilized. A much higher amount (~5%) of the total arsenic was mobilized into the liquid phase. Through the application of molecular tools, including 16S rRNA sequencing and quantification of gene transcripts involved in methanogenesis, this study links microbial community activity with arsenic fate in potential disposal environments. These results illustrate that disposal of arsenic-bearing wastes by mixing with cow dung does not achieve its end goal of promoting arsenic volatilization but rather appears to increase arsenic mobilization in the aqueous phase, raising concerns with this approach.

  19. Arsenic in Drinking Water-A Global Environmental Problem

    Science.gov (United States)

    Wang, Joanna Shaofen; Wai, Chien M.

    2004-01-01

    Information on the worldwide occurrence of groundwater pollution by arsenic, the ensuing health hazards, and the debatable government regulations of arsenic in drinking water, is presented. Diagnostic identification of arsenic, and methods to eliminate it from water are also discussed.

  20. Epidemiologic evidence of diabetogenic effect of arsenic.

    Science.gov (United States)

    Tseng, Chin-Hsiao; Tseng, Ching-Ping; Chiou, Hung-Yi; Hsueh, Yu-Mei; Chong, Choon-Khim; Chen, Chien-Jen

    2002-07-01

    It is well documented that arsenic can lead to skin lesions, atherosclerotic diseases and cancers. The association between arsenic exposure and diabetes mellitus is a relatively new finding. Up to now, there are six epidemiologic reports linking diabetes mellitus with arsenic exposure from environmental and occupational sources. Two reports in Taiwan carried out in the blackfoot disease-hyperendemic villages, one cross-sectional and one prospective follow-up of the same cohort, indicate that arsenic exposure from drinking artesian well water is associated with prevalence and incidence of diabetes mellitus in a dose-responsive pattern. The observation of the relation between arsenic exposure and diabetes mellitus is further supported by studies carried out in Sweden and Bangladesh. In Sweden, case-control analyses of death records of copper smelters and glass workers revealed a trend of increasing diabetes mellitus with increasing arsenic exposure from inhalation. In Bangladesh, prevalence of diabetes mellitus among arsenic-exposed subjects with keratosis was about five times higher than unexposed subjects. Increasing trends of diabetes mellitus with indices of arsenic exposure in drinking water seems to be independent of the presence of skin lesions associated with arsenic exposure. Although these studies consistently show an association between arsenic exposure and diabetes mellitus, the weak study designs of cross-sectional or case-control, the use of glucosuria or diabetes death as diagnostic criteria and the lack of adjustment for possible confounders in some studies, are major limitations that may reduce the strength of the evidence. PMID:12076511

  1. Sequestration of arsenic in ombrotrophic peatlands

    Science.gov (United States)

    Rothwell, James; Hudson-Edwards, Karen; Taylor, Kevin; Polya, David; Evans, Martin; Allott, Tim

    2014-05-01

    Peatlands can be important stores of arsenic but we are lacking spectroscopic evidence of the sequestration pathways of this toxic metalloid in peatland environments. This study reports on the solid-phase speciation of anthropogenically-derived arsenic in atmospherically contaminated peat from the Peak District National Park (UK). Surface and sub-surface peat samples were analysed by synchrotron X-ray absorption spectroscopy on B18 beamline at Diamond Light Source (UK). The results suggest that there are contrasting arsenic sequestration mechanisms in the peat. The bulk arsenic speciation results, in combination with strong arsenic-iron correlations at the surface, suggest that iron (hydr)oxides are key phases for the immobilisation of arsenic at the peat surface. In contrast, the deeper peat samples are dominated by arsenic sulphides (arsenopyrite, realgar and orpiment). Given that these peats receive inputs solely from the atmosphere, the presence of these sulphide phases suggests an in-situ authigenic formation. Redox oscillations in the peat due to a fluctuating water table and an abundant store of legacy sulphur from historic acid rain inputs may favour the precipitation of arsenic sequestering sulphides in sub-surface horizons. Oxidation-induced loss of these arsenic sequestering sulphur species by water table drawdown has important implications for the mobility of arsenic and the quality of waters draining peatlands.

  2. Arsenic removal from drinking water during coagulation

    Energy Technology Data Exchange (ETDEWEB)

    Hering, J.G. [California Inst. of Tech., Pasadena, CA (United States); Chen, P.Y. [Industrial Technology Research Inst., Chutung Hsinchu (Taiwan, Province of China); Wilkie, J.A.; Elimelech, M. [Univ. of California, Los Angeles, CA (United States). Dept. of Civil and Environmental Engineering

    1997-08-01

    The efficiency of arsenic removal from source waters and artificial freshwaters during coagulation with ferric chloride and alum was examined in bench-scale studies. Arsenic(V) removal by either ferric chloride or alum was relatively insensitive to variations in source water composition below pH 8. At pH 8 and 9, the efficiency of arsenic(V) removal by ferric chloride was decreased in the presence of natural organic matter. The pH range for arsenic(V) removal with alum was more restricted than with ferric chloride. For source waters spiked with 20 {micro}g/L arsenic(V), final dissolved arsenic(V) concentrations in the product water of less than 2 {micro}g/L were achieved with both coagulants at neutral pH. Removal of arsenic(III) from source waters by ferric chloride was both less efficient and more strongly influenced by source water composition than removal of arsenic(V). The presence of sulfate (at pH 4 and 5) and natural organic matter (at pH 4 through 9) adversely affected the efficiency of arsenic(III) removal by ferric chloride. Arsenic(III) could not be removed from source waters by coagulation with alum.

  3. Acute arsenic poisoning diagnosed late.

    Science.gov (United States)

    Shumy, Farzana; Anam, Ahmad Mursel; Kamruzzaman, A K M; Amin, Md Robed; Chowdhury, M A Jalil

    2016-04-01

    Acute arsenicosis, although having a 'historical' background, is not common in our times. This report describes a case of acute arsenic poisoning, missed initially due to its gastroenteritis-like presentation, but suspected and confirmed much later, when the patient sought medical help for delayed complications after about 2 months.

  4. The microbial genomics of arsenic.

    Science.gov (United States)

    Andres, Jérémy; Bertin, Philippe N

    2016-03-01

    Arsenic, which is a major contaminant of many aquatic ecosystems worldwide, is responsible for serious public health issues. However, life has evolved various strategies for coping with this toxic element. In particular, prokaryotic organisms have developed processes enabling them to resist and metabolize this chemical. Studies based on genome sequencing and transcriptome, proteome and metabolome profiling have greatly improved our knowledge of prokaryotes' metabolic potential and functioning in contaminated environments. The increasing number of genomes available and the development of descriptive and comparative approaches have made it possible not only to identify several genetic determinants of the arsenic metabolism, but also to elucidate their phylogenetic distribution and their modes of regulation. In addition, studies using functional genomic tools have established the pleiotropic character of prokaryotes' responses to arsenic, which can be either common to several species or species-specific. These approaches also provide promising means of deciphering the functioning of microbial communities including uncultured organisms, the genetic transfers involved and the possible occurrence of metabolic interactions as well as the evolution of arsenic resistance and metabolism.

  5. Acute arsenic poisoning diagnosed late.

    Science.gov (United States)

    Shumy, Farzana; Anam, Ahmad Mursel; Kamruzzaman, A K M; Amin, Md Robed; Chowdhury, M A Jalil

    2016-04-01

    Acute arsenicosis, although having a 'historical' background, is not common in our times. This report describes a case of acute arsenic poisoning, missed initially due to its gastroenteritis-like presentation, but suspected and confirmed much later, when the patient sought medical help for delayed complications after about 2 months. PMID:26508422

  6. Arsenic chemistry in soils and sediments

    Energy Technology Data Exchange (ETDEWEB)

    Fendorf, S.; Nico, P.; Kocar, B.D.; Masue, Y.; Tufano, K.J.

    2009-10-15

    Arsenic is a naturally occurring trace element that poses a threat to human and ecosystem health, particularly when incorporated into food or water supplies. The greatest risk imposed by arsenic to human health results from contamination of drinking water, for which the World Health Organization recommends a maximum limit of 10 {micro}g L{sup -1}. Continued ingestion of drinking water having hazardous levels of arsenic can lead to arsenicosis and cancers of the bladder, skin, lungs and kidneys. Unfortunately, arsenic tainted drinking waters are a global threat and presently having a devastating impact on human health within Asia. Nearly 100 million people, for example, are presently consuming drinking water having arsenic concentrations exceeding the World Health Organization's recommended limit (Ahmed et al., 2006). Arsenic contamination of the environment often results from human activities such as mining or pesticide application, but recently natural sources of arsenic have demonstrated a devastating impact on water quality. Arsenic becomes problematic from a health perspective principally when it partitions into the aqueous rather than the solid phase. Dissolved concentrations, and the resulting mobility, of arsenic within soils and sediments are the combined result of biogeochemical processes linked to hydrologic factors. Processes favoring the partitioning of As into the aqueous phase, potentially leading to hazardous concentrations, vary extensively but can broadly be grouped into four categories: (1) ion displacement, (2) desorption (or limited sorption) at pH values > 8.5, (3) reduction of arsenate to arsenite, and (4) mineral dissolution, particularly reductive dissolution of Fe and Mn (hydr)oxides. Although various processes may liberate arsenic from solids, a transition from aerobic to anaerobic conditions, and commensurate arsenic and iron/manganese reduction, appears to be a dominant, but not exclusive, means by which high concentrations of

  7. Synergistic effects in mixed Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Reisner, A.; Holler, B.M.; Molin, Søren;

    2006-01-01

    the pathways governing development of more complex heterogeneous communities. In this study, we established a laboratory model where biofilm-stimulating effects due to interactions between genetically diverse strains of Escherichia coli were monitored. Synergistic induction of biofilm formation resulting from...... the cocultivation of 403 undomesticated E. coli strains with a characterized E. coli K-12 strain was detected at a significant frequency. The survey suggests that different mechanisms underlie the observed stimulation, yet synergistic development of biofilm within the subset of E. coli isolates (n = 56) exhibiting...... the strongest effects was most often linked to conjugative transmission of natural plasmids carried by the E. coli isolates (70%). Thus, the capacity of an isolate to promote the biofilm through cocultivation was (i) transferable to the K-12 strain, (ii) was linked with the acquisition of conjugation genes...

  8. An evaluation of arsenic release from monolithic solids using a modified semi-dynamic leaching test.

    Science.gov (United States)

    Dermatas, Dimitris; Moon, Deok Hyun; Menounou, Nektaria; Meng, Xiaoguang; Hires, Richard

    2004-12-10

    Quicklime and quicklime-fly ash-based stabilization/solidification (S/S) effectiveness was evaluated by performing semi-dynamic leaching tests (American Nuclear Society 16.1). Artificial soil samples, contaminated with arsenic trioxide (As2O3) as well as field soil samples contaminated with arsenic (As) were tested. The artificial soils were prepared by mixing amounts of kaolinite or montmorillonite with fine quartz sand. The S/S effectiveness was evaluated by measuring effective diffusion coefficients (De) and leachability indices (LX). Treatment was most effective in kaolinite-based artificial soils treated with quicklime and in quicklime-fly ash treated field soils. The experimental results indicate that De values were lowered as a result of S/S treatment. Upon treatment LX values were higher than 9, suggesting that S/S treated soils are acceptable for "controlled utilization". Based on a model developed by de Groot and van der Sloot [G.J. de Groot, H.A. van der Sloot, in: T.M. Gilliam, C.C. Wiles (Eds.), Stabilization and Solidification of Hazardous, Radioactive, and Mixed Wastes, vol. 2, ASTM STP 1123, ASTM, PA, 1992, p. 149], the leaching mechanism for all of the treated soils was found to be controlled by diffusion. The effect of soluble silica (Si) on As leachability was also evaluated. When soluble Si concentration was less than 1 ppm, As leachability was the lowest. The controlling mechanism of As immobilization whether sorption, precipitation, or inclusion was also evaluated. It was determined that precipitation was the dominant mechanism. PMID:15561360

  9. Synergistic modeling of call center operations

    OpenAIRE

    2006-01-01

    We synergistically apply queueing theory, integer programming, and stochastic simulation to determine an optimal staffing policy for a repair call handling center. A stationary Markovian queueing model is employed to determine minimal staffing levels for a sequence of time intervals with varying call volumes and mean handling times. These staffing requirements populate an integer program model for determining the mix of call agent shifts that will achieve service quality standards at minimum ...

  10. Culture and neuroscience: additive or synergistic?

    OpenAIRE

    Losin, Elizabeth A. Reynolds; DAPRETTO, MIRELLA; Iacoboni, Marco

    2010-01-01

    The investigation of cultural phenomena using neuroscientific methods—cultural neuroscience (CN)—is receiving increasing attention. Yet it is unclear whether the integration of cultural study and neuroscience is merely additive, providing additional evidence of neural plasticity in the human brain, or truly synergistic, yielding discoveries that neither discipline could have achieved alone. We discuss how the parent fields to CN: cross-cultural psychology, psychological anthropology and cogni...

  11. Arsenic Contamination in Food-chain: Transfer of Arsenic into Food Materials through Groundwater Irrigation

    OpenAIRE

    Huq, S.M. Imamul; Joardar, J.C.; Parvin, S.; Correll, Ray; Naidu, Ravi

    2006-01-01

    Arsenic contamination in groundwater in Bangladesh has become an additional concern vis-à-vis its use for irrigation purposes. Even if arsenic-safe drinking-water is assured, the question of irrigating soils with arsenic-laden groundwater will continue for years to come. Immediate attention should be given to assess the possibility of accumulating arsenic in soils through irrigation-water and its subsequent entry into the food-chain through various food crops and fodders. With this possibilit...

  12. Arsenic adsorption of lateritic soil, limestone powder, lime and fly ash on arsenic-contaminated soil

    OpenAIRE

    Wuthiphun, L.; Towatana, P.; Arrykul, S.; V. Chongsuvivatwong

    2007-01-01

    Arsenic adsorption efficiency of soil covering materials (lateritic soil, limestone powder, lime and fly ash) on arsenic-contaminated soil obtained from Ronpiboon District, Nakhon Sri Thammarat Province tosolve arsenic air pollution problem was investigated using batch experiments. The four types of the aforementioned soil covering materials were examined to determine their arsenic adsorption efficiency, equilibriumtime as well as adsorption isotherms.The results revealed that among soil cove...

  13. Outbreak of arsenic and toxaphene poisoning in Kenyan cattle. [Arsenic was detected in cattle dips

    Energy Technology Data Exchange (ETDEWEB)

    Maitai, C.K.; Kamau, J.A.; Gacuhi, D.M.; Njoroge, S.

    1975-02-15

    In a case of poisoning involving 70 cattle analysis of specimens obtained during post mortem examination showed that the toxic substances were arsenic and toxaphene. This was consistent with both the clinical and post mortem findings. Arsenic was detected in water from an abandoned cattle dip in the farm. Soil samples collected in the vicinity of the dip contained both arsenic and toxaphene.

  14. Method of arsenic removal from water

    Energy Technology Data Exchange (ETDEWEB)

    Gadgil, Ashok (El Cerrito, CA)

    2010-10-26

    A method for low-cost arsenic removal from drinking water using chemically prepared bottom ash pre-treated with ferrous sulfate and then sodium hydroxide. Deposits on the surface of particles of bottom ash form of activated iron adsorbent with a high affinity for arsenic. In laboratory tests, a miniscule 5 grams of pre-treated bottom ash was sufficient to remove the arsenic from 2 liters of 2400 ppb (parts per billion) arsenic-laden water to a level below 50 ppb (the present United States Environmental Protection Agency limit). By increasing the amount of pre-treated bottom ash, even lower levels of post-treatment arsenic are expected. It is further expected that this invention supplies a very low-cost solution to arsenic poisoning for large population segments.

  15. Arsenic--state of the art.

    Science.gov (United States)

    Landrigan, P J

    1981-01-01

    Approximately 1.5 million workers in the United States are exposed to arsenic. Occupational exposure is primarily by inhalation. NIOSH recommends that time-integrated exposure to arsenic in air not exceed 2 micrograms/m3. Recent exposure is accurately measured by urine assay; urine arsenic concentrations above 50 micrograms/liter indicate increased absorption. Hair assay is a semiquantitative index of past exposure. Toxicity is associated primarily with the trivalent (3+) form of arsenic. Acute poisoning is caused most commonly by contaminated food or drink; it is rarely occupational. Chronic intoxication is characterized by dermatitis, hyperpigmentation, keratoses, peripheral neuropathy (primarily sensory), irritation of the upper and lower respiratory tract, and occasionally by hepatic toxicity and peripheral vasculopathy (blackfoot disease). Arsenic is not carcinogenic in animal species, but is mutagenic in Syrian hamster cells. In man, arsenic is known definitely to cause cancer of skin, lung, and liver (angiosarcoma) and possibly to cause lymphoma.

  16. Pulp Revascularization in Immature Permanent Tooth with Apical Periodontitis Using Mineral Trioxide Aggregate

    Directory of Open Access Journals (Sweden)

    Katsura Saeki

    2014-01-01

    Full Text Available Mineral trioxide aggregate (MTA is a material that has been used worldwide in several clinical applications, such as apical barriers in teeth with immature apices, repair of root perforations, root-end filling, pulp capping, and pulpotomy. The purpose of this case report was to describe successful revascularization treatment of an immature mandibular right second premolar with apical periodontitis in a 9-year-old female patient. After preparing an access cavity without anesthesia, the tooth was isolated using a rubber dam and accessed. The canal was gently debrided using 5% sodium hypochlorite (NaOCl and 3% hydrogen peroxide irrigant. And then MTA was packed into the canal. X-ray photographic examination showed the dentin bridge 5 months after the revascularization procedure. Thickening of the canal wall and complete apical closure were confirmed 10 months after the treatment. In this case, MTA showed clinical and radiographic success at revascularization treatment in immature permanent tooth. The successful outcome of this case suggests that MTA is reliable and effective for endodontic treatment in the pediatric dentistry.

  17. In vitro investigations into the etiology of mineral trioxide tooth staining

    Directory of Open Access Journals (Sweden)

    Todd Berger

    2014-01-01

    Full Text Available Aim: To investigate the role of bismuth oxide, a constituent of contemporary mineral trioxide aggregate (MTA materials, and its response to various solutions that may contribute to the potential discoloration that occurs following MTA applications within the scope of endodontics. Setting and Design: Laboratory assessment of chemical reactions with white ProRoot® MTA and white Portland cement (WPC. Materials and Methods: Set specimens and freshly mixed specimens of white ProRoot® MTA and white ProRoot® MTA powder, along with specimens of WPC were exposed to distilled water, phosphate buffered saline (PBS, 10% formalin, hydroxyethylmethacrylate (HEMA, sodium hypochlorite, sodium hydroxide (NaOH base, and hydrochloric acid (HCl acid. Specimens were visually inspected periodically for color changes. Results: All forms of ProRoot MTA showed discoloration when exposed to 10% formalin within 30 min, as opposed to WPC, and were completely blackened at 4 days. Bismuth oxide alone and with calcium oxide also turned black within 30 min after exposure to 10% formalin. No discoloration was seen when exposed to the other solutions. Conclusions: Exposing MTA in various forms to a variety of liquids has determined that bismuth oxidein combination with other chemical moieties is the prime cause of staining observed by clinicians.

  18. Comparative Performance of Mineral Trioxide Aggregate Versus Calcium Hydroxide as a Direct Pulp Capping Agent.

    Science.gov (United States)

    Jefferies, Steven R

    2016-03-01

    Vital pulp therapy is the general concept involved in the "regenerative" restorative treatment of the reversibly injured dental pulp with the intention of maintaining its vitality in a restored, functioning tooth. While this procedure has been attempted with various materials and techniques over a period of several centuries, the advent of hard-setting calcium hydroxide materials in the late 1950s made the procedure of direct pulp capping a more routine and relatively predictable procedure. More recently, in the mid 1990s, a new type of water-based, "hydraulic-type," calcium silicate-based cement, mineral trioxide aggregate (MTA), was introduced to dentistry as a possible alternative to the established standard of hard-setting calcium hydroxide. Over the last two decades, a slowly growing body of pre-clinical and human clinical studies evaluating and comparing these two materials has developed. Most recently, a number of well-designed, randomized controlled studies and resultant systematic reviews have been completed and published regarding the comparative efficacy of calcium hydroxide versus MTA for direct pulp capping. This Critical Appraisal considers and reviews some of the more recently published reports which provide a more definitive answer to this clinical research question. PMID:26876369

  19. Evaluation of mineral trioxide aggregate as root canal sealer: A clinical study

    Directory of Open Access Journals (Sweden)

    Sophia Thakur

    2013-01-01

    Full Text Available Aim: The aim of this study was to compare the clinical and radiological outcome of mineral trioxide aggregate (MTA or epoxy resin as a root canal sealer compared with zinc oxide eugenol sealer. Materials and Methods: 45 single rooted teeth with periapical index Score 2 or more were allotted to three groups with 15 teeth in each group. Root canal treatment was performed in two visits and obturated with Gutta-percha as obturating material and zinc oxide eugenol as sealer in Group 1, epoxy resin as sealer in Group 2 and MTA mixed with propylene glycol as sealer in Group 3. Visual analog scale, periapical index and VixWin digital Pro image analysis software were used for evaluation. The quantitative data was analyzed by t-test and analysis of variance. Ordinal data was analyzed by Wilcoxon′s signed rank test, Mann-Whitney and Kruskall-Wallis test. Results: Results suggested that there exists no statistically significant difference in clinical or radiological outcome of root canal therapy with three different types of sealers used in this study. Conclusions: MTA could be used as a root canal sealer with equal effectiveness compared with epoxy resin and zinc oxide eugenol sealers. Further long-term studies should be carried out to prove the effectiveness.

  20. Dynamic intratubular biomineralization following root canal obturation with pozzolan‐based mineral trioxide aggregate sealer cement

    Science.gov (United States)

    Yoo, Yeon‐Jee; Baek, Seung‐Ho; Kum, Kee‐Yeon; Shon, Won‐Jun; Woo, Kyung‐Mi

    2015-01-01

    Summary The application of mineral trioxide aggregates (MTA) cement during the root canal obturation is gaining concern due to its bioactive characteristic to form an apatite in dentinal tubules. In this regard, this study was to assess the biomineralization of dentinal tubules following root canal obturation by using pozzolan‐based (Pz‐) MTA sealer cement (EndoSeal MTA, Maruchi). Sixty curved roots (mesiobuccal, distobuccal) from human maxillary molars were instrumented and prepared for root canal obturation. The canals were obturated with gutta‐percha (GP) and Pz‐MTA sealer by using continuous wave of condensation technique. Canals obturated solely with ProRoot MTA (Dentsply Tulsa Dental) or Pz‐MTA sealer were used for comparison. In order to evaluate the biomineralization ability under different conditions, the PBS pretreatment before the root canal obturation was performed in each additional samples. At dentin‐material interfaces, the extension of intratubular biomineralization was analyzed using scanning electron microscopy (SEM) and energy dispersive spectroscopy. When the root canal was obturated with GP and Pz‐MTA sealer, enhanced biomineralization of the dentinal tubules beyond the penetrated sealer tag was confirmed under the SEM observation (p cement can be used as a promising bioactive root canal sealer to enhance biomineralization of dentinal tubules under controlled environment. SCANNING 38:50–56, 2016. © 2015 The Authors. Scanning Published by Wiley Periodicals, Inc. PMID:26179659

  1. Dynamic intratubular biomineralization following root canal obturation with pozzolan-based mineral trioxide aggregate sealer cement.

    Science.gov (United States)

    Yoo, Yeon-Jee; Baek, Seung-Ho; Kum, Kee-Yeon; Shon, Won-Jun; Woo, Kyung-Mi; Lee, WooCheol

    2016-01-01

    The application of mineral trioxide aggregates (MTA) cement during the root canal obturation is gaining concern due to its bioactive characteristic to form an apatite in dentinal tubules. In this regard, this study was to assess the biomineralization of dentinal tubules following root canal obturation by using pozzolan-based (Pz-) MTA sealer cement (EndoSeal MTA, Maruchi). Sixty curved roots (mesiobuccal, distobuccal) from human maxillary molars were instrumented and prepared for root canal obturation. The canals were obturated with gutta-percha (GP) and Pz-MTA sealer by using continuous wave of condensation technique. Canals obturated solely with ProRoot MTA (Dentsply Tulsa Dental) or Pz-MTA sealer were used for comparison. In order to evaluate the biomineralization ability under different conditions, the PBS pretreatment before the root canal obturation was performed in each additional samples. At dentin-material interfaces, the extension of intratubular biomineralization was analyzed using scanning electron microscopy (SEM) and energy dispersive spectroscopy. When the root canal was obturated with GP and Pz-MTA sealer, enhanced biomineralization of the dentinal tubules beyond the penetrated sealer tag was confirmed under the SEM observation (p cement can be used as a promising bioactive root canal sealer to enhance biomineralization of dentinal tubules under controlled environment.

  2. The Composition and Biologic Actions of Mineral Trioxide Aggregate: A Review

    Directory of Open Access Journals (Sweden)

    Toptancı İR et al.

    2013-06-01

    Full Text Available Aim: Mineral Trioxide Aggregate (MTA is widely used in clinical application such as pulp capping, perforation repair, root-end sealing, canal filling at internal and external root resorption and pulpotomies in primary and permanent teeth. In endodontic field when using a material such as MTA the interaction between material and periapical tissue is so important for healing and life time of endodontic therapy. Although it is sealing ability, the interaction with cells or tissues and their replay to this material play major role for endodontic success. Methods: Literature review was performed using electronic and hand-searching methods for the clinical applications, experimental studies and cellular studies of MTA between 2000 and 2010. Results: MTA is a bioactive material when using vital pulpotomies, apical barrier formation for necrotic pulps and open apices. Numerous study and case reports show MTA is more effective material than other materials in these cases. Many studies have shown the effects of MTA on cementoblasts and odontoblasts. Conclusion: This review shows its composition, biologic action when used different endodontic procedure and interaction between cell and tissues.

  3. Immediate and delayed solubility of mineral trioxide aggregate and Portland cement

    Directory of Open Access Journals (Sweden)

    Augusto Bodanezi

    2008-04-01

    Full Text Available This study investigated the solubility of mineral trioxide aggregate (MTA and Portland cement since its mixture until 672 hours, by means of two complimentary methods. Metal ring molds filled with the cements were covered with distilled water and, at each experimental time (3, 24, 72, 168, 336 and 672 hours, were weighed as soon as the plates in which the samples have been placed. Empty rings served as the control group (n=8. Mean weight gain and loss was determined and analyzed statistically by two-way ANOVA and Tukey's test for all pairwise comparisons. Only Portland cement showed less than 3% weight loss through 24 hours. Detached MTA residues were heavier than those of Portland cement over the 3 to 168 hours. The weight of MTA rings increased more than that of Portland rings within 672 hours (p=0.05. The findings of the present study indicate that, in an aqueous environment MTA is more soluble than Portland cement and exceeds the maximum weight loss considered acceptable by ISO 6876 standard (2001.

  4. Tooth discoloration induced by a novel mineral trioxide aggregate-based root canal sealer

    Science.gov (United States)

    Lee, Dae-Sung; Lim, Myung-Jin; Choi, Yoorina; Rosa, Vinicius; Hong, Chan-Ui; Min, Kyung-San

    2016-01-01

    Objectives: The aim of this study was to evaluate tooth discoloration caused by contact with a novel injectable mineral trioxide aggregate (MTA)-based root canal sealer (Endoseal; Maruchi, Wonju, Korea) compared with a widely used resin-based root canal sealer (AHplus; Dentsply De Trey, Konstanz, Germany) and conventional MTA (ProRoot; Dentsply, Tulsa, OK, USA). Materials and Methods: Forty standardized bovine tooth samples were instrumented and divided into three experimental groups and one control group (n = 10/group). Each material was inserted into the cavity, and all specimens were sealed with a self-adhesive resin. Based on CIE Lab system, brightness change (ΔL) and total color change (ΔE) of each specimen between baseline and 1, 2, 4, and 8 weeks were obtained. Results: At all time points, Endoseal showed no significant difference in ΔL and ΔE compared to AHplus and control group (P > 0.05), whereas the ProRoot group showed significantly higher ΔL and ΔE values than the Endoseal group at 2, 4, and 8 weeks (P MTA and a similar color change to AHplus. Conclusions: Within the limitations of this study, our data indicate that the MTA-based sealer produces a similar amount of tooth discoloration as AHplus which is considered to be acceptable. PMID:27403062

  5. Tandem organic light-emitting diode with a molybdenum tri-oxide thin film interconnector layer

    Institute of Scientific and Technical Information of China (English)

    Lu Fei-Ping; Wang Qian; Zhou Xiang

    2013-01-01

    A 10-nm-thick molybdenum tri-oxide (MoO3) thin film was used as the interconnector layer in tandem organic lightemitting devices (OLEDs).The tandem OLEDs with two identical emissive units consisting of N,N'-bis(naphthalen-1-yl)-N,N'-bis(phenyl)-benzidine (NPB) / tris(8-hydroxyquinoline) aluminum (Alq3) exhibited current efficiency-current density characteristics superior to the conventional single-unit devices.At 20 mA/cm2,the current efficiency of the tandem OLEDs using the interconnector layers of MoO3 thin film was about 4.0 cd/A,which is about twice that of the corresponding conventional single-unit device (1.8 cd/A).The tandem OLED showed a higher power efficiency than the conventional single-unit device for luminance over 1200 cd/m2.The experimental results demonstrated that a MoO3 thin film with a proper thickness can be used as an effective interconnector layer in tandem OLEDs.Such an interconnector layer can be easily fabricated by simple thermal evaporation,greatly simplifying the device processing and fabrication processes required by previously reported interconnector layers.A possible explanation was proposed for the carrier generation of the MoO3 interconnector layer.

  6. Effect of Dentin Bonding Agent on the Prevention of Tooth Discoloration Produced by Mineral Trioxide Aggregate

    Directory of Open Access Journals (Sweden)

    Majid Akbari

    2012-01-01

    Full Text Available Objective. Determination of the effect of dentin bonding agent (DBA on the prevention of tooth discoloration produced by mineral trioxide aggregate (MTA. Methods. 50 teeth were endodontically treated and after removal of 3 mm of obturating materials were divided into five groups. In white MTA (WMTA and grey MTA (GMTA groups, these materials were placed in root canal below the orifice. In DBA + WMTA and DBA + GMTA groups, DBAs were applied in the access cavity. Then, 3 mm of WMTA and GMTA was placed. The last 10 teeth served as control. All of teeth were restored and color measurement was recorded for each specimen at this time and 6 months later. Results. The mean tooth discoloration in WMTA and GMTA groups was significantly more than DBA + WMTA and DBA + GMTA groups, respectively. There was no significant difference between DBA + WMTA and DBA + GMTA groups and control group. Conclusion. Application of DBA before MTA may prevent tooth discoloration.

  7. Amido Rhenium Trioxides: Cases of Hindered Agostic C-H-M Interactions?

    CERN Document Server

    Benndorf, P; Roesky, P W; Eickerling, G; Scherer, W

    2008-01-01

    The amido rhenium trioxides of composition (iPr2N)ReO3, (iPrCyN)ReO3 and (Cy2N)ReO3 (Cy = cyclohexyl) were synthesized in a one pot reaction starting from Re2O7, Me3SiCl and the corresponding amines (iPr)2NH, (iPr)(Cy)NH, and (Cy)2NH, respectively. In the solid state the amido ligands of all three complexes are asymmetrically coordinated to the ReO3 core allowing for one short Re-H-C contact in each case which might indicate the presence of beta-agostic interaction. However, analysis of the charge density distribution provided us clear-cut criteria that beta-agostic interactions are suppressed by the trans-influence of the oxo-groups. Comparison with structurally related tetra-coordinated d0 titanium amido complexes highlighted a systematic concept how the extent of beta-agostic interactions in these complexes can be controlled by reducing the trans-influence of the co-ligands. We therefore suggest to employ the expression "hindered agostic interactions" in cases where covalent M-H-C are in principle supporte...

  8. Arsenic stress after the Proterozoic glaciations

    OpenAIRE

    Ernest Chi Fru; Emma Arvestål; Nolwenn Callac; Abderrazak El Albani; Stephanos Kilias; Ariadne Argyraki; Martin Jakobsson

    2015-01-01

    Protection against arsenic damage in organisms positioned deep in the tree of life points to early evolutionary sensitization. Here, marine sedimentary records reveal a Proterozoic arsenic concentration patterned to glacial-interglacial ages. The low glacial and high interglacial sedimentary arsenic concentrations, suggest deteriorating habitable marine conditions may have coincided with atmospheric oxygen decline after ~2.1 billion years ago. A similar intensification of near continental mar...

  9. Presence of Arsenic in Commercial Beverages

    Directory of Open Access Journals (Sweden)

    Jason Roberge

    2009-01-01

    Full Text Available Problem statement: This study’s goal was to assess the arsenic concentration of various beverages and broths purchased from a local chain supermarket. A source of chronic arsenic exposure occurs via food and beverage consumption. Groundwater levels of total arsenic are regulated (-1 by the Environmental Protection Agency (EPA but few studies have examined arsenic concentrations in common beverages. Approach: In the initial analysis of 19 items, total arsenic concentration was assessed from a variety of fruit juices, sports drinks, sodas and broths. Items found to contain levels of total arsenic ≥5.0 µg L-1 were further evaluated. Additional analysis included purchasing multiple brands of items ≥5.0 µg L-1and analyzing them for total arsenic and chemical species of arsenic. Results: Among the beverages in the initial analysis, apple juice (10.79 µg L-1 and grape juice (49.87 µg L-1 contained the highest levels of total arsenic. Upon examination of items with As concentrations above 5.0 µg L-1, varying concentrations of total arsenic were found in apple cider (range: 5.41-15.27 µg L-1, apple juice (range: 10.67-22.35 µg L-1, baby fruit juice (range: 13.91-16.51 µg L-1 and grape juice (range: 17.69-47.59 µg L-1. Conclusion: Many commercially available juices contained concentrations of arsenic that were higher than the standard for total arsenic allowed in groundwater as set forth by the EPA. The concentration of As in these juices varied between and within brands. In general, those consuming apple and grape juices are the young and elderly and it is these populations that may be more vulnerable to over exposure of heavy metals.

  10. Arsenic Toxicity in Male Reproduction and Development

    OpenAIRE

    Kim, Yoon-Jae; Kim, Jong-Min

    2015-01-01

    Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic a...

  11. Certain cases of poisoning by arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Cristol, P.; Fourcade, J.; Ravoire, J.; Bezenech, C.

    1939-05-01

    Cases of acute and chronic poisoning by arsenic are reported. Diffuse pains, angor, edema of the limbs and genitals, complicated by heptic insufficiency and chronic bronchitis were determined in a subject having lived near an industrial plant processing arseniferous ores for several years. The plant emitted several hundred kg of finely dispersed arsenic oxide daily which settled on forage and vegetables. Symptoms of poisoning by arsenic were also detected in cattle in the same area. The installation of Cottrell type dust separators has helped to suppress the arsenic oxide emissions.

  12. Arsenic-bound excitons in diamond

    Science.gov (United States)

    Barjon, J.; Jomard, F.; Morata, S.

    2014-01-01

    A set of new excitonic recombinations is observed in arsenic-implanted diamond. It is composed of two groups of emissions at 5.355/5.361 eV and at 5.215/5.220/5.227 eV. They are respectively attributed to the no-phonon and transverse-optical phonon-assisted recombinations of excitons bound to neutral arsenic donors. From the Haynes rule, an ionization energy of 0.41 eV is deduced for arsenic in diamond, which shows that arsenic is a shallower donor than phosphorus (0.6 eV), in agreement with theory.

  13. Arsenic and antimony transporters in eukaryotes.

    Science.gov (United States)

    Maciaszczyk-Dziubinska, Ewa; Wawrzycka, Donata; Wysocki, Robert

    2012-01-01

    Arsenic and antimony are toxic metalloids, naturally present in the environment and all organisms have developed pathways for their detoxification. The most effective metalloid tolerance systems in eukaryotes include downregulation of metalloid uptake, efflux out of the cell, and complexation with phytochelatin or glutathione followed by sequestration into the vacuole. Understanding of arsenic and antimony transport system is of high importance due to the increasing usage of arsenic-based drugs in the treatment of certain types of cancer and diseases caused by protozoan parasites as well as for the development of bio- and phytoremediation strategies for metalloid polluted areas. However, in contrast to prokaryotes, the knowledge about specific transporters of arsenic and antimony and the mechanisms of metalloid transport in eukaryotes has been very limited for a long time. Here, we review the recent advances in understanding of arsenic and antimony transport pathways in eukaryotes, including a dual role of aquaglyceroporins in uptake and efflux of metalloids, elucidation of arsenic transport mechanism by the yeast Acr3 transporter and its role in arsenic hyperaccumulation in ferns, identification of vacuolar transporters of arsenic-phytochelatin complexes in plants and forms of arsenic substrates recognized by mammalian ABC transporters.

  14. Acute arsenic poisoning in two siblings.

    Science.gov (United States)

    Lai, Melisa W; Boyer, Edward W; Kleinman, Monica E; Rodig, Nancy M; Ewald, Michele Burns

    2005-07-01

    We report a case series of acute arsenic poisoning of 2 siblings, a 4-month-old male infant and his 2-year-old sister. Each child ingested solubilized inorganic arsenic from an outdated pesticide that was misidentified as spring water. The 4-month-old child ingested a dose of arsenic that was lethal despite extraordinary attempts at arsenic removal, including chelation therapy, extracorporeal membrane oxygenation, exchange transfusion, and hemodialysis. The 2-year-old fared well with conventional therapy. PMID:15995066

  15. XAS Studies of Arsenic in the Environment

    International Nuclear Information System (INIS)

    Arsenic is present in low concentrations in much of the Earth's crust and changes in its speciation are vital to understanding its transport and toxicity in the environment. We have used X-ray absorption spectroscopy to investigate the coordination sites of arsenic in a wide variety of samples, including soil and earthworm tissues from arsenic-contaminated land, and human hair and nail samples from people exposed to arsenic in Cambodia. Our results confirm the effectiveness of using X-ray absorption near edge structure (XANES) and X-ray absorption fine structure (EXAFS) spectroscopy to determine speciation changes in environmental samples

  16. Arsenic in the soils of Zimapan, Mexico

    International Nuclear Information System (INIS)

    Arsenic concentrations of 73 soil samples collected in the semi-arid Zimapan Valley range from 4 to 14 700 mg As kg-1. Soil arsenic concentrations decrease with distance from mines and tailings and slag heaps and exceed 400 mg kg-1 only within 500 m of these arsenic sources. Soil arsenic concentrations correlate positively with Cu, Pb, and Zn concentrations, suggesting a strong association with ore minerals known to exist in the region. Some As was associated with Fe and Mn oxyhydroxides, this association is less for contaminated than for uncontaminated samples. Very little As was found in the mobile water-soluble or exchangeable fractions. The soils are not arsenic contaminated at depths greater than 100 cm below the surface. Although much of the arsenic in the soils is associated with relatively immobile solid phases, this represents a long-term source of arsenic to the environment. -- Much of the arsenic is relatively immobile but presents long-term source of arsenic

  17. [Tracing for arsenic exposure--a differentiation of arsenic compounds is essential for the health assessment].

    Science.gov (United States)

    Weistenhöfer, Wobbeke; Ochsmann, Elke; Drexler, Hans; Göen, Thomas; Klotz, Katrin

    2016-01-01

    Arsenic is ubiquitous and harmful to health in occupation and environment. Arsenic exposure is measured through analysis of arsenic compounds in urine. The identification of several arsenic species is necessary to understand the hazardous potential of the arsenic compounds which differ highly in their toxicity. To estimate the extent of an occupational exposure to arsenic, arsenic species were evaluated for the first time by the working group "Setting of Threshold Limit Values in Biological Material" of the DFG Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area and Biologische Arbeitsstoffreferenzwerte (BAR) of 0.5 μg / L urine for arsenic (III), 0.5 μg / L urine for arsenic (V), 2 μg / L urine for monomethylarsonic acid (MMA) and 10 μg / L urine for dimethylarsinic acid (DMA) were set. If the reference value for total arsenic is exceeded, a further differentiation of arsenic species now enables to estimate the individual health risks taking into account special influences such as seafood consumption.

  18. Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype

    International Nuclear Information System (INIS)

    Inorganic arsenic is enzymatically methylated; hence, its ingestion results in exposure to the parent compound and various methylated arsenicals. Both experimental and epidemiological evidences suggest that some of the adverse health effects associated with chronic exposure to inorganic arsenic may be mediated by these methylated metabolites. If i As methylation is an activation process, then the phenotype for inorganic arsenic methylation may determine risk associated with exposure to this metalloid. We examined inorganic arsenic methylation phenotypes and arsenic (+3 oxidation state) methyltransferase genotypes in four species: three that methylate inorganic arsenic (human (Homo sapiens), rat (Rattus norwegicus), and mouse (Mus musculus)) and one that does not methylate inorganic arsenic (chimpanzee, Pan troglodytes). The predicted protein products from arsenic (+3 oxidation state) methyltransferase are similar in size for rat (369 amino acid residues), mouse (376 residues), and human (375 residues). By comparison, a 275-nucleotide deletion beginning at nucleotide 612 in the chimpanzee gene sequence causes a frameshift that leads to a nonsense mutation for a premature stop codon after amino acid 205. The null phenotype for inorganic arsenic methylation in the chimpanzee is likely due to the deletion in the gene for arsenic (+3 oxidation state) methyltransferase that yields an inactive truncated protein. This lineage-specific loss of function caused by the deletion event must have occurred in the Pan lineage after Homo-Pan divergence about 5 million years ago

  19. Interactions between arsenic species and marine algae

    Energy Technology Data Exchange (ETDEWEB)

    Sanders, J.G.

    1978-01-01

    The arsenic concentration and speciation of marine algae varies widely, from 0.4 to 23 ng.mg/sup -1/, with significant differences in both total arsenic content and arsenic speciation occurring between algal classes. The Phaeophyceae contain more arsenic than other algal classes, and a greater proportion of the arsenic is organic. The concentration of inorganic arsenic is fairly constant in macro-algae, and may indicate a maximum level, with the excess being reduced and methylated. Phytoplankton take up As(V) readily, and incorporate a small percentage of it into the cell. The majority of the As(V) is reduced, methylated, and released to the surrounding media. The arsenic speciation in phytoplankton and Valonia also changes when As(V) is added to cultures. Arsenate and phosphate compete for uptake by algal cells. Arsenate inhibits primary production at concentrations as low as 5 ..mu..g.1/sup -1/ when the phosphate concentration is low. The inhibition is competitive. A phosphate enrichment of > 0.3 ..mu..M alleviates this inhibition; however, the As(V) stress causes an increase in the cell's phosphorus requirement. Arsenite is also toxic to phytoplankton at similar concentrations. Methylated arsenic species did not affect cell productivity, even at concentrations of 25 ..mu..g.1/sup -1/. Thus, the methylation of As(V) by the cell produces a stable, non-reactive compound which is nontoxic. The uptake and subsequent reduction and methylation of As(V) is a significant factor in determining the arsenic biogeochemistry of productive systems, and also the effect that the arsenic may have on algal productivity. Therefore, the role of marine algae in determining the arsenic speciation of marine systems cannot be ignored. (ERB)

  20. Arsenic mobilization and immobilization in paddy soils

    Science.gov (United States)

    Kappler, A.; Hohmann, C.; Zhu, Y. G.; Morin, G.

    2010-05-01

    Arsenic is oftentimes of geogenic origin and in many cases bound to iron(III) minerals. Iron(III)-reducing bacteria can harvest energy by coupling the oxidation of organic or inorganic electron donors to the reduction of Fe(III). This process leads either to dissolution of Fe(III)-containing minerals and thus to a release of the arsenic into the environment or to secondary Fe-mineral formation and immobilisation of arsenic. Additionally, aerobic and anaerobic iron(II)-oxidizing bacteria have the potential to co-precipitate or sorb arsenic during iron(II) oxidation at neutral pH that is usually followed by iron(III) mineral precipitation. We are currently investigating arsenic immobilization by Fe(III)-reducing bacteria and arsenic co-precipitation and immobilization by anaerobic iron(II)-oxidizing bacteria in batch, microcosm and rice pot experiments. Co-precipitation batch experiments with pure cultures of nitrate-dependent Fe(II)-oxidizing bacteria are used to quantify the amount of arsenic that can be immobilized during microbial iron mineral precipitation, to identify the minerals formed and to analyze the arsenic binding environment in the precipitates. Microcosm and rice pot experiments are set-up with arsenic-contaminated rice paddy soil. The microorganisms (either the native microbial population or the soil amended with the nitrate-dependent iron(II)-oxidizing Acidovorax sp. strain BoFeN1) are stimulated either with iron(II), nitrate, or oxygen. Dissolved and solid-phase arsenic and iron are quantified. Iron and arsenic speciation and redox state in batch and microcosm experiments are determined by LC-ICP-MS and synchrotron-based methods (EXAFS, XANES).

  1. Arsenic Adsorption Onto Iron Oxides Minerals

    Science.gov (United States)

    Aredes, S.; Klein, B.; Pawlik, M.

    2004-12-01

    The predominant form of arsenic in water is as an inorganic ion. Under different redox conditions arsenic in water is stable in the +5 and +3 oxidation states. Arsenic oxidation state governs its toxicity, chemical form and solubility in natural and disturbed environments. As (III) is found in anoxic environments such as ground water , it is toxic and the common species is the neutral form, H3AsO3. As (V) is found in aerobic conditions such as surface water, it is less toxic and the common species in water are: H2AsO4 - and HAsO4 {- 2}. The water pH determines the predominant arsenate or arsenite species, however, both forms of arsenic can be detected in natural water systems. Iron oxides minerals often form in natural waters and sediments at oxic-anoxic boundaries. Over time they undergo transformation to crystalline forms, such as goethite or hematite. Both As(V) and As(III) sorbs strongly to iron oxides, however the sorption behavior of arsenic is dependent on its oxidation state and the mineralogy of the iron oxides. Competition between arsenic and others ions, such fluoride, sulphate and phosphate also play a role. On the other hand, calcium may increase arsenic adsorption onto iron oxides. Electrokinetic studies and adsorption experiments were carried out in order to determine which conditions favour arsenic adsorption. Hematite, goethite and magnetite as iron based sorbents were used. Test were also conducted with a laterite soil rich in iron minerals. The focus of this study is to evaluate physical and chemical conditions which favour arsenic adsorption onto iron oxides minerals, the results contribute to an understanding of arsenic behaviour in natural and disturbed environments. Furthermore, results could contribute in developing an appropriate remediation technology for arsenic removal in water using iron oxides minerals.

  2. Chromosome analysis of arsenic affected cattle

    Directory of Open Access Journals (Sweden)

    S. Shekhar

    2014-10-01

    Full Text Available Aim: The aim was to study the chromosome analysis of arsenic affected cattle. Materials and Methods: 27 female cattle (21 arsenic affected and 6 normal were selected for cytogenetical study. The blood samples were collected, incubated, and cultured using appropriate media and specific methods. The samples were analyzed for chromosome number and morphology, relative length of the chromosome, arm ratio, and centromere index of X chromosome and chromosomal abnormalities in arsenic affected cattle to that of normal ones. Results: The diploid number of metaphase chromosomes in arsenic affected cattle as well as in normal cattle were all 2n=60, 58 being autosomes and 2 being sex chromosomes. From the centromeric position, karyotyping studies revealed that all the 29 pair of autosomes was found to be acrocentric or telocentric, and the sex chromosomes (XX were submetacentric in both normal and arsenic affected cattle. The relative length of all the autosome pairs and sex chrosomosome pair was found to be higher in normal than that of arsenic affected cattle. The mean arm ratio of X-chromosome was higher in normal than that of arsenic affected cattle, but it is reverse in case of centromere index value of X-chromosome. There was no significant difference of arm ratio and centromere index of X-chromosomes between arsenic affected and normal cattle. No chromosomal abnormalities were found in arsenic affected cattle. Conclusion: The chromosome analysis of arsenic affected cattle in West Bengal reported for the first time in this present study which may serve as a guideline for future studies in other species. These reference values will also help in comparison of cytological studies of arsenic affected cattle to that of various toxicants.

  3. Chitosan-Pectin Synergistic Interaction and Gelation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Mixed gels of chitosan-pectin were prepared by varying the ratio of constituents in the presence of NaCl. Mixed gel at 3% of total polysaccharide concentration with addtion of 12% NaCl showed a synergistic maximum when the ratio of chitosan to pectin was 60 : 40. The effect of the polysaccharide concentration,the preparation temperature(Tp), the time of incubation, balk salt concentration, the molecular weight and the degree of deacetylation of chitosan on gelation have been studied. Interaction mechanism between molecules of both polysaccharides was investigated by FT-IR spectrometry.

  4. ARSENIC REMOVAL AND ECOLOGICALLY SAFE CONTAINMENT OF ARSENIC-WASTE: A SUSTAINABLE SOLUTION FOR ARSENIC CRISIS IN CAMBODIA

    Science.gov (United States)

    An appalling degree of arsenic contamination in groundwater has affected more than a million people in wide region of Mekong delta flood plain in Cambodia. Arsenic is by far the most toxic species of all naturally occurring groundwater contaminants and disposal of removed arse...

  5. Arsenic Removal by Liquid Membranes

    Directory of Open Access Journals (Sweden)

    Tiziana Marino

    2015-03-01

    Full Text Available Water contamination with harmful arsenic compounds represents one of the most serious calamities of the last two centuries. Natural occurrence of the toxic metal has been revealed recently for 21 countries worldwide; the risk of arsenic intoxication is particularly high in Bangladesh and India but recently also Europe is facing similar problem. Liquid membranes (LMs look like a promising alternative to the existing removal processes, showing numerous advantages in terms of energy consumption, efficiency, selectivity, and operational costs. The development of different LM configurations has been a matter of investigation by several researching groups, especially for the removal of As(III and As(V from aqueous solutions. Most of these LM systems are based on the use of phosphine oxides as carriers, when the metal removal is from sulfuric acid media. Particularly promising for water treatment is the hollow fiber supported liquid membrane (HFSLM configuration, which offers high selectivity, easy transport of the targeted metal ions, large surface area, and non-stop flow process. The choice of organic extractant(s plays an essential role in the efficiency of the arsenic removal. Emulsion liquid membrane (ELM systems have not been extensively investigated so far, although encouraging results have started to appear in the literature. For such LM configuration, the most relevant step toward efficiency is the choice of the surfactant type and its concentration.

  6. Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China.

    Science.gov (United States)

    Liu, Jie; Zheng, Baoshan; Aposhian, H Vasken; Zhou, Yunshu; Chen, Ming-Liang; Zhang, Aihua; Waalkes, Michael P

    2002-02-01

    Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here we report the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China. Coal in this region has undergone mineralization and thus produces high concentrations of arsenic. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such overexposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area.

  7. Improving chemical vapor deposition graphene conductivity using molybdenum trioxide: An in-situ field effect transistor study

    International Nuclear Information System (INIS)

    By using in situ field effect transistor characterization integrated with molecular beam epitaxy technique, we demonstrate the strong surface transfer p-type doping effect of single layer chemical vapor deposition (CVD) graphene, through the surface functionalization of molybdenum trioxide (MoO3) layer. After doping, both the hole and electron mobility of CVD graphene are nearly retained, resulting in significant enhancement of graphene conductivity. With coating of 10 nm MoO3, the conductivity of CVD graphene can be increased by about 7 times, showing promising application for graphene based electronics and transparent, conducting, and flexible electrodes

  8. Porous dimanganese trioxide microflowers derived from microcoordinations for flexible solid-state asymmetric supercapacitors

    Science.gov (United States)

    Pang, Huan; Li, Xinran; Li, Bing; Zhang, Yizhou; Zhao, Qunxing; Lai, Wen-Yong; Huang, Wei

    2016-06-01

    Dimanganese trioxide microflowers are easily obtained from a Mn(ii) 8-hydroxyquinoline microcoordination after calcination in air. We also look into the possible formation mechanism of the flower-like morphology, and find that the reaction time affects the morphology of the coordination. Furthermore, the as-prepared porous Mn2O3 microflowers are made of many nanoplates which form many nanogaps and nanochannels. Interestingly, the assembled electrode based on the as-prepared porous Mn2O3 microflowers proves to be a high-performance electrode material for supercapacitors. The electrode shows a specific capacitance of 994 F g-1, which can work well even after 4000 cycles at 0.75 A g-1. More importantly, the porous Mn2O3 microflowers and activated carbons are assembled into a high-performance flexible solid-state asymmetric supercapacitor with a specific capacitance of 312.5 mF cm-2. The cycle test shows that the device can offer 95.6% capacity of the initial capacitance at 2.0 mA cm-2 after 5000 cycles with little decay. The maximum energy density of the device can achieve 6.56 mWh cm-3 and the maximum power density can also achieve 283.5 mW cm-3, which are among the best results for manganese based materials.Dimanganese trioxide microflowers are easily obtained from a Mn(ii) 8-hydroxyquinoline microcoordination after calcination in air. We also look into the possible formation mechanism of the flower-like morphology, and find that the reaction time affects the morphology of the coordination. Furthermore, the as-prepared porous Mn2O3 microflowers are made of many nanoplates which form many nanogaps and nanochannels. Interestingly, the assembled electrode based on the as-prepared porous Mn2O3 microflowers proves to be a high-performance electrode material for supercapacitors. The electrode shows a specific capacitance of 994 F g-1, which can work well even after 4000 cycles at 0.75 A g-1. More importantly, the porous Mn2O3 microflowers and activated carbons are

  9. The apical leakage of mineral trioxide aggregate as the retrograde filling material with various mixing agents

    Directory of Open Access Journals (Sweden)

    Ema Mulyawati

    2010-06-01

    Full Text Available Background: Mineral trioxide aggregate (MTA is relatively considered as a new material in endodontic. It even has been used as retrograde filling material due to its biocompatibility, antibacterial effect, sealing ability and anti-moist effect. Some materials have been used as mixing agent to achieve an appropiate setting of MTA. Purpose: The aim of this study is to investigate the effect of the mixing agents of MTA towards the apical leakage when they are used together as retrograde filling materials. Method: The samples of this research consist of 30 human extracted upper central incisors. First, the crown of each tooth is sectioned. The root canals are prepared by using the conventional technique and then are obturated with gutta percha. After cutting the root apex, 2 mm from apical, class 1 cavities are prepared by using fissure bur with the depth of 3 mm. The samples then are divided into 3 groups with 10 teeth for each. Group I uses aquabidest as mixing agent of MTA (MTA-aquabidest, group II uses saline (MTA-saline, while group III uses 0.12% chlorhexidine (MTA-chlorhexidine. The apex of each group then is filled with the mixing MTA determined already. Afterwards, clearing method is used to evaluate the apical leakage. The apical leakage actually is determined by measuring the depth of methylene blue penetration with stereomicroscope. The statictical analyses of the linear dye penetration then are performed with analysis of varians ANOVA. Result: The dye penetration for both MTA-aquadest and MTA-saline groups indicates the lowest penetration, and there is even a significant difference compared with MTA-0.12% chlorhexidine group (p<0.005. Conclusion: It can be concluded that aquabidest and saline as mixing agents of MTA produce less apical leakage compared with 0.12% chlorhexidine.Latar belakang: Mineral trioxide aggregate (MTA merupakan bahan yang relatif baru dalam bidang endodontik. Bahan tersebut diindikasikan sebagai bahan pengisi

  10. Preparation of nanostructured tungsten trioxide thin films by high pressure sublimation and condensation

    Energy Technology Data Exchange (ETDEWEB)

    Abdel Samad, B., E-mail: bassel.abdel.samad@umoncton.ca; Thibodeau, J.; Ashrit, P.V.

    2015-09-30

    Highlights: • A new technique combines the high pressure sublimation and condensation with the variation of source–substrate distance to control the thin film nanostructure. • The nanostructure of WO{sub 3} thin films is systematically controlled in terms of the grain size and porosity. • The dependence of nanostructure, roughness, grain size, porosity and index of refraction to the source–substrate distance is studied. • The potential tailoring of the film properties for solar energy applications through the precise control of film nanostructure is suggested. - Abstract: Thin films of tungsten trioxide (WO{sub 3}) have gained increasing importance due to their interesting chromogenic properties and for their high application potential in electrochromic devices. It is very well known that their electrochromic switching properties depend very sensitively on their nanostructure. Hence, a vast majority of the research work carried out in this domain at present is dedicated to the various techniques of controlled inducing of a nanostructure in these WO{sub 3} thin films in order to enhance their electrochromic performance. In the present work we have carried out a systematic study of the nanostructured WO{sub 3} thin films by using a novel technique of varying the source–substrate distance in a high pressure sublimation and condensation method. This technique has been found to be very efficient in controlling the grain size and thus the nanostructure of the deposited films. A correlation is established between the optical and electrochromic properties of the WO{sub 3} films and the induced nanostructure. The electrochromic properties are studied by a dry lithiation process developed in our laboratory. The results indicate a strong dependence of the film nanostructure on the source–substrate distance which influences quite sensitively the electrochromic properties. These results are expected to help design electrochromic devices suitable for different

  11. Evaluation of pulpotomy in primary molars with mineral trioxide aggregate and formocresol

    Directory of Open Access Journals (Sweden)

    Aeinehchi M

    2007-01-01

    Full Text Available Background and Aim: Vital pulpotomy in primary teeth is performed to maintain the vitality of the pulp and tooth until normal exfoliation. Different materials such as zinc oxide- eugenol, calcium hydroxide and formocresol are used in this procedure. The aim of this study was to evaluate the application of formocresol (FC and mineral trioxide aggregate (MTA in pulpotomy of primary molars. Materials and Methods: In this clinical trial, one hundred and twenty six children (aged 5 to 9 years old with dental caries that were candidate for pulpotomy were selected and randomly divided into two groups. After removing the roof of the pulp chamber, coronal pulp was cut at the orifices and bleeding controlled. In control group, formocresol was applied for 5 minutes. In case group, MTA paste was used as pulpotomy agent. The crowns of both groups were restored with amalgam and the teeth were evaluated clinically and radiographically after 3 and 6 months follow up. Data were analyzed by Fisher test with p<0.05 as the limit of significance. Results: No sign of clinical failure was observed after 3 and 6 months follow-up. Comparison between the two methods revealed no significant difference in radiographic findings of the teeth and surrounding tissues after 3 months follow-up. However, after 6 months follow-up, internal resorption was observed radiographically in four cases of formocresol group. Conclusion: Based on the results of this study, pulpotomy with MTA showed more successful results than formocresol radiographically. MTA is recommended as a good substitute for formocresol in pulpotomy of primary molars.

  12. In vitro chemical and cellular tests applied to uranium trioxide with different hydration states

    International Nuclear Information System (INIS)

    A simple and rapid in vitro chemical solubility test applicable to industrial uranium trioxide (UO3) was developed together with two in vitro cellular tests using rat alveolar macrophages maintained either in gas phase or in alginate beads at 37 degrees C. Industrial UO3 was characterized by particle size, X-ray, and IR spectra, and chemical transformation (e.g., aging and hydration of the dust) was also studied. Solvents used for the in vitro chemical solubility study included carbonates, citrates, phosphates, water, Eagle's basal medium, and Gamble's solution (simulated lung fluid), alone, with oxygen, or with superoxide ions. Results, expressed in terms of the half-time of dissolution, according to International Commission on Radiological Protection (ICRP) classification (D,W,Y), varied for different hydration states of UO3, showing a lower solubility of hydrated UO3 in solvents compared to basic UO3 or UO3 heated at 450 degrees C. Two in vitro cellular tests on cultured rat alveolar macrophages (cells maintained in gas phase and cells immobilized in alginate beads) were used on the same UO3 samples and generally showed a lower solution transfer rate in the presence of macrophages than in the culture medium alone. The results of in vitro chemical and cellular tests were compared, with four main conclusions; a good reproducibility of the three tests in Eagle's basal medium of the effect of hydration state on solubility, the classification of UO3 in terms of ICRP solubility criteria, and the ability of macrophoges to decrease uranium solubility in medium. 16 refs., 3 figs., 4 tabs

  13. Comparison of Tooth Discoloration Induced by Calcium-Enriched Mixture and Mineral Trioxide Aggregate

    Science.gov (United States)

    Rouhani, Armita; Akbari, Majid; Farhadi-faz, Aida

    2016-01-01

    Introduction: The aim of this in vitro study was to evaluate the tooth discoloration induced by calcium-enriched mixture (CEM) cement and mineral trioxide aggregate (MTA). Methods and Materials: Forty five endodontically treated human maxillary central incisors were selected and divided into three groups (n=15) after removing the coronal 3 mm of the obturating materials. In the MTA group, white MTA plug was placed in pulp chamber and coronal zone of the root canal. In CEM cement group, CEM plug was placed in the tooth in the same manner. In both groups, a wet cotton pellet was placed in the access cavity and the teeth were temporarily sealed. After 24 h the teeth were restored with resin composite. In the negative control group the teeth were also restored with resin composite. The color change in the cervical third of teeth was measured with a colorimeter and was repeated 3 times for each specimen. The teeth were kept in artificial saliva for 6 months. After this period, the color change was measured again. Data were collected by Commission International de I'Eclairage's L*a*b color values, and corresponding ΔE values were calculated. The results were analyzed using the one-way ANOVA and post-hoc Tukey’s test with the significance level defined as 0.05. Results: There was no significant differences between CEM group and control group in mean discoloration. The mean tooth discoloration in MTA group was significantly greater than CEM and control groups (P<0.05). Conclusion: According to the result of the present study CEM cement did not induce tooth discoloration after six months. Therefore it can be used in vital pulp therapy of esthetically sensitive teeth. PMID:27471526

  14. Mineral Trioxide Aggregate vs. Calcium Hydroxide in Primary Molar Pulpotomy: A Systematic Review

    Science.gov (United States)

    Shirvani, Armin; Hassanizadeh, Raheleh; Asgary, Saeed

    2014-01-01

    Introduction: The aim of this quantitative systematic review/meta-analysis was to compare the treatment outcomes of mineral trioxide aggregate (MTA) and calcium hydroxide (CH) in pulpotomy of human primary molars. The focused PICO question was “in case of pulp exposure in vital primary molars, how does MTA pulpotomy compare to CH in terms of clinical/radiographic success?” Methods and Materials: We retrieved published randomized clinical trials (RCTs) of at least 6-month duration; our search included articles published up to March 2013 in five following databases: PubMed (Medline), Cochrane database of systematic reviews, Science Citation Index, EMBASE, and Google Scholar. Mantel Haenszel and Inverse Variance-weighted methods were applied by STATA; the relative risk (RR) was calculated with 95% confidence intervals (CI). Results: A total of 282 English articles were collected. Two authors independently screened the articles and five RCTs were selected; data extraction and quality assessment were then carried out. Four RCTs were appropriate for meta-analysis according to their follow-up times by Mantel Haenszel method. Statistically significant difference was found between success rate of MTA compared to CH, with RR=0.08 (95% CI, 0.02-0.39), RR=0.19 (95% CI, 0.08-0.46), and RR=0.38 (95% CI, 0.21-0.68) for 6-, 12-, and 24-month follow-ups, respectively. A significant difference was also observed for all included RCTs after analyses using the Inverse Variance-weighted method (RR=0.44; 95% CI, 0.27-0.72). Conclusions: Systematic review/meta-analysis of included RCTs revealed that for pulpotomy of vital primary molars, MTA has better treatment outcomes compared to CH. PMID:24688575

  15. Bioaccumulation of Arsenic by Fungi

    Directory of Open Access Journals (Sweden)

    Ademola O. Adeyemi

    2009-01-01

    Full Text Available Problem statement: Arsenic is a known toxic element and its presence and toxicity in nature is a worldwide environmental problem. The use of microorganisms in bioremediation is a potential method to reduce as concentration in contaminated areas. Approach: In order to explore the possible bioremediation of this element, three filamentous fungi-Aspergillus niger, Serpula himantioides and Trametes versicolor were investigated for their potential abilities to accumulate (and possibly solubilize arsenic from an agar environment consisting of non buffered mineral salts media amended with 0.2, 0.4, 0.6 and 0.8% (w/v arsenopyrite (FeAsS. Growth rates, dry weights, arsenic accumulation and oxalate production by the fungi as well as the pH of the growth media were all assessed during this study. Results: There was no visible solubilization of FeAsS particles underneath any of the growing fungal colonies or elsewhere in the respective agar plates. No specific patterns of growth changes were observed from the growth ratios of the fungi on agar amended with different amounts of FeAsS although growth of all fungi was stimulated by the incorporation of varying amounts of FeAsS into the agar with the exception of A. niger on 0.4% (w/v amended agar and T. versicolor on 0.8% (w/v amended agar. The amounts of dry weights obtained for all three fungi also did not follow any specific patterns with different amounts of FeAsS and the quantities obtained were in the order A. niger > S. himantioides > T. versicolor. All fungi accumulated as in their biomasses with all amounts of FeAsS although to varying levels and T. versicolor was the most effective with all amounts of FeAsS while A. niger was the least effective. Conclusion: The accumulation of arsenic in the biomasses of the test fungi as shown in this study may suggested a role for fungi through their bioaccumulating capabilities as agents in the possible bioremediation of arsenic contaminated environments.

  16. Hijacking membrane transporters for arsenic phytoextraction.

    Science.gov (United States)

    LeBlanc, Melissa S; McKinney, Elizabeth C; Meagher, Richard B; Smith, Aaron P

    2013-01-10

    Arsenic is a toxic metalloid and recognized carcinogen. Arsenate and arsenite are the most common arsenic species available for uptake by plants. As an inorganic phosphate (Pi) analog, arsenate is acquired by plant roots through endogenous Pi transport systems. Inside the cell, arsenate is reduced to the thiol-reactive form arsenite. Glutathione (GSH)-conjugates of arsenite may be extruded from the cell or sequestered in vacuoles by members of the ATP-binding cassette (ABC) family of transporters. In the present study we sought to enhance both plant arsenic uptake through Pi transporter overexpression, and plant arsenic tolerance through ABC transporter overexpression. We demonstrate that Arabidopsis thaliana plants overexpressing the high-affinity Pi transporter family members, AtPht1;1 or AtPht1;7, are hypersensitive to arsenate due to increased arsenate uptake. These plants do not exhibit increased sensitivity to arsenite. Co-overexpression of the yeast ABC transporter YCF1 in combination with AtPht1;1 or AtPht1;7 suppresses the arsenate-sensitive phenotype while further enhancing arsenic uptake. Taken together, our results support an arsenic transport mechanism in which arsenate uptake is increased through Pi transporter overexpression, and arsenic tolerance is enhanced through YCF1-mediated vacuolar sequestration. This work substantiates the viability of coupling enhanced uptake and vacuolar sequestration as a means for developing a prototypical engineered arsenic hyperaccumulator.

  17. 29 CFR 1915.1018 - Inorganic arsenic.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Inorganic arsenic. 1915.1018 Section 1915.1018 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1018 Inorganic arsenic. Note: The requirements applicable to shipyard employment under...

  18. Biotechnology based processes for arsenic removal

    NARCIS (Netherlands)

    Huisman, J.; Olde Weghuis, M.; Gonzalez-Contreras, P.A.

    2011-01-01

    The regulations for arsenic control have become strict. Therefore, better technologies to remove arsenic from bleeds and effluents are desired. In addition, no single solution is suitable for all cases. The properties of the process streams and the storage facilities are major factors determining th

  19. Arsenic and human health effects: A review.

    Science.gov (United States)

    Abdul, Khaja Shameem Mohammed; Jayasinghe, Sudheera Sammanthi; Chandana, Ediriweera P S; Jayasumana, Channa; De Silva, P Mangala C S

    2015-11-01

    Arsenic (As) is ubiquitous in nature and humans being exposed to arsenic via atmospheric air, ground water and food sources are certain. Major sources of arsenic contamination could be either through geological or via anthropogenic activities. In physiological individuals, organ system is described as group of organs that transact collectively and associate with other systems for conventional body functions. Arsenic has been associated with persuading a variety of complications in body organ systems: integumentary, nervous, respiratory, cardiovascular, hematopoietic, immune, endocrine, hepatic, renal, reproductive system and development. In this review, we outline the effects of arsenic on the human body with a main focus on assorted organ systems with respective disease conditions. Additionally, underlying mechanisms of disease development in each organ system due to arsenic have also been explored. Strikingly, arsenic has been able to induce epigenetic changes (in utero) and genetic mutations (a leading cause of cancer) in the body. Occurrence of various arsenic induced health effects involving emerging areas such as epigenetics and cancer along with their respective mechanisms are also briefly discussed.

  20. 29 CFR 1926.1118 - Inorganic arsenic.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false Inorganic arsenic. 1926.1118 Section 1926.1118 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Inorganic arsenic. Note: The requirements applicable to construction work under this section are...

  1. Arsenic Consumption in the United States.

    Science.gov (United States)

    Wilson, Denise

    2015-10-01

    Exposure limits for arsenic in drinking water and minimal risk levels (MRLs) for total dietary exposure to arsenic have long been established in the U.S. Multiple studies conducted over the last five years have detected arsenic in foods and beverages including juice, rice, milk, broth (beef and chicken), and others. Understanding whether or not each of these foods or drinks is a concern to certain groups of individuals requires examining which types of and how much arsenic is ingested. In this article, recent studies are reviewed and placed in the context of consumption patterns. When single sources of food or drink are considered in isolation, heavy rice eaters can be exposed to the most arsenic among adults while infants consuming formula containing contaminated organic brown rice syrup are the most exposed group among children. Most food and drink do not contain sufficient arsenic to exceed MRLs. For individuals consuming more than one source of contaminated water or food, however, adverse health effects are more likely. In total, recent studies on arsenic contamination in food and beverages emphasize the need for individual consumers to understand and manage their total dietary exposure to arsenic. PMID:26591332

  2. ARSENIC EFFECTS ON TELOMERE AND TELOMERASE ACTIVITY

    Science.gov (United States)

    Arsenic effects on telomere and telomerase activity. T-C. Zhang, M. T. Schmitt, J. Mo, J. L. Mumford, National Research Council and U.S Environmental Protection Agency, NHEERL, Research Triangle Park, NC 27711Arsenic is a known carcinogen and also an anticancer agent for acut...

  3. Arsenic pesticides and environmental pollution: exposure, poisoning, hazards and recommendations.

    Science.gov (United States)

    El-Bahnasawy, Mamdouh M; Mohammad, Amina El-Hosini; Morsy, Tosson A

    2013-08-01

    Arsenic is a metalloid element. Acute high-dose exposure to arsenic can cause severe systemic toxicity and death. Lower dose chronic arsenic exposure can result in subacute toxicity that can include peripheral sensorimotor neuropathy, skin eruptions, and hepatotoxicity. Long-term effects of arsenic exposure include an in Due to the physiologic effects of the arsenic on all body systems, thus, chronic arsenic-poisoned patient is a major nursing challenge. The critical care nurse provides valuable assessment and interventions that prevent major multisystem complications from arsenic toxicity.

  4. Research plan for arsenic in drinking water

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-02-01

    The document stresses the implications of recent research findings and emphasizes identification of key strengths and sources of uncertainty and variability in the arsenic risk assessment. This document also explains how information gained through research can: impact the method used in new investigations to assess the risks of arsenic, and support or suggest changes in the assumptiosn and methods used in arsenic risk assessments. This Arsenic Research Plan addresses the protection of human health, especially the research needed to implement the 1996 Safe Drinking Water Act Amendments (SDWAA). It is intended to serve as a blueprint that will be discussed with parties interested in addressing key strengths and uncertainties in the arsenic risk assessment.

  5. Arsenic in Drinking Water—A Global Environmental Problem

    Science.gov (United States)

    Shaofen Wang, Joanna; Wai, Chien M.

    2004-02-01

    Arsenic contamination of groundwater is a global environmental problem affecting a large number of populations, especially in developing countries. The "blackfoot disease"that occurred in Taiwan more than half of a century ago was attributed to drinking arsenic-contaminated water from deep wells containing high concentrations of the trivalent arsenite species. Similar arsenic poisoning cases were reported later in Chinese Inner Mongolia, Bangladesh, and India—all related to drinking groundwater contaminated with arsenic. The maximum contaminant level (MCL) of arsenic in drinking water has been changed recently by the U.S. EPA from 50 ppb to 10 ppb; the compliance date is January 2006. This article summarizes documented global arsenic contamination problems, the regulatory controversy regarding MCL of arsenic in drinking water, and available technologies for removing arsenic from contaminated waters. Methods for analyzing total arsenic and arsenic species in water are also described.

  6. Arsenic Uptake by Muskmelon (Cucumis melo) Plants from Contaminated Water.

    Science.gov (United States)

    Hettick, Bryan E; Cañas-Carrell, Jaclyn E; Martin, Kirt; French, Amanda D; Klein, David M

    2016-09-01

    Arsenic is a carcinogenic element that occurs naturally in the environment. High levels of arsenic are found in water in some parts of the world, including Texas. The aims of this study were to determine the distribution of arsenic in muskmelon (Cucumis melo) plants accumulated from arsenic spiked water and to observe effects on plant biomass. Plants were grown and irrigated using water spiked with variable concentrations of arsenic. Inductively coupled plasma mass spectrometry was used to quantify arsenic in different parts of the plant and fruit. Under all conditions tested in this study, the highest concentrations of arsenic were found in the leaves, soil, and roots. Arsenic in the water had no significant effect on plant biomass. Fruits analyzed in this study had arsenic concentrations of 101 μg/kg or less. Consuming these fruits would result in less arsenic exposure than drinking water at recommended levels. PMID:27460822

  7. Arsenic burden survey among refuse incinerator workers

    Directory of Open Access Journals (Sweden)

    Chao Chung-Liang

    2005-01-01

    Full Text Available Background: Incinerator workers are not considered to have arsenic overexposure although they have the risk of overexposure to other heavy metals. Aim: To examine the relationship between arsenic burden and risk of occupational exposure in employees working at a municipal refuse incinerator by determining the concentrations of arsenic in the blood and urine. Settings and Design: The workers were divided into three groups based on their probability of contact with combustion-generated residues, namely Group 1: indirect contact, Group 2: direct contact and Group 3: no contact. Healthy age- and sex-matched residents living in the vicinity were enrolled as the control group. Materials and Methods: Heavy metal concentrations were measured by atomic absorption spectrophotometer. Downstream rivers and drinking water of the residents were examined for environmental arsenic pollution. A questionnaire survey concerning the contact history of arsenic was simultaneously conducted. Statistical analysis: Non-parametric tests, cross-tabulation and multinomial logistic regression. Results: This study recruited 122 incinerator workers. The urine and blood arsenic concentrations as well as incidences of overexposure were significantly higher in the workers than in control subjects. The workers who had indirect or no contact with combustion-generated residues had significantly higher blood arsenic level. Arsenic contact history could not explain the difference. Airborne and waterborne arsenic pollution were not detected. Conclusion: Incinerator workers run the risk of being exposed to arsenic pollution, especially those who have incomplete protection in the workplace even though they only have indirect or no contact with combustion-generated pollutants.

  8. Factors Affecting Elevated Arsenic and Methyl Mercury Concentrations in Small Shield Lakes Surrounding Gold Mines near the Yellowknife, NT, (Canada Region.

    Directory of Open Access Journals (Sweden)

    Adam James Houben

    Full Text Available Gold mines in the Yellowknife, NT, region--in particular, the Giant Mine--operated from 1949-99, releasing 237,000 tonnes of waste arsenic trioxide (As2O3 dust, among other compounds, from gold ore extraction and roasting processes. For the first time, we show the geospatial distribution of roaster-derived emissions of several chemical species beyond the mine property on otherwise undisturbed taiga shield lakes within a 25 km radius of the mine, 11 years after its closing. Additionally, we demonstrate that underlying bedrock is not a significant source for the elevated concentrations in overlying surface waters. Aquatic arsenic (As concentrations are well above guidelines for drinking water (10 μg/L and protection for aquatic life (5 μg/L, ranging up to 136 μg/L in lakes within 4 km from the mine, to 2.0 μg/L in lakes 24 km away. High conversion ratios of methyl mercury were shown in lakes near the roaster stack as well, with MeHg concentrations reaching 44% of total mercury. The risk of elevated exposures by these metals is significant, as many lakes used for recreation and fishing near the City of Yellowknife are within this radius of elevated As and methyl Hg concentrations.

  9. Factors Affecting Elevated Arsenic and Methyl Mercury Concentrations in Small Shield Lakes Surrounding Gold Mines near the Yellowknife, NT, (Canada) Region.

    Science.gov (United States)

    Houben, Adam James; D'Onofrio, Rebecca; Kokelj, Steven V; Blais, Jules M

    2016-01-01

    Gold mines in the Yellowknife, NT, region--in particular, the Giant Mine--operated from 1949-99, releasing 237,000 tonnes of waste arsenic trioxide (As2O3) dust, among other compounds, from gold ore extraction and roasting processes. For the first time, we show the geospatial distribution of roaster-derived emissions of several chemical species beyond the mine property on otherwise undisturbed taiga shield lakes within a 25 km radius of the mine, 11 years after its closing. Additionally, we demonstrate that underlying bedrock is not a significant source for the elevated concentrations in overlying surface waters. Aquatic arsenic (As) concentrations are well above guidelines for drinking water (10 μg/L) and protection for aquatic life (5 μg/L), ranging up to 136 μg/L in lakes within 4 km from the mine, to 2.0 μg/L in lakes 24 km away. High conversion ratios of methyl mercury were shown in lakes near the roaster stack as well, with MeHg concentrations reaching 44% of total mercury. The risk of elevated exposures by these metals is significant, as many lakes used for recreation and fishing near the City of Yellowknife are within this radius of elevated As and methyl Hg concentrations. PMID:27050658

  10. Factors Affecting Elevated Arsenic and Methyl Mercury Concentrations in Small Shield Lakes Surrounding Gold Mines near the Yellowknife, NT, (Canada) Region.

    Science.gov (United States)

    Houben, Adam James; D'Onofrio, Rebecca; Kokelj, Steven V; Blais, Jules M

    2016-01-01

    Gold mines in the Yellowknife, NT, region--in particular, the Giant Mine--operated from 1949-99, releasing 237,000 tonnes of waste arsenic trioxide (As2O3) dust, among other compounds, from gold ore extraction and roasting processes. For the first time, we show the geospatial distribution of roaster-derived emissions of several chemical species beyond the mine property on otherwise undisturbed taiga shield lakes within a 25 km radius of the mine, 11 years after its closing. Additionally, we demonstrate that underlying bedrock is not a significant source for the elevated concentrations in overlying surface waters. Aquatic arsenic (As) concentrations are well above guidelines for drinking water (10 μg/L) and protection for aquatic life (5 μg/L), ranging up to 136 μg/L in lakes within 4 km from the mine, to 2.0 μg/L in lakes 24 km away. High conversion ratios of methyl mercury were shown in lakes near the roaster stack as well, with MeHg concentrations reaching 44% of total mercury. The risk of elevated exposures by these metals is significant, as many